BCCDC TB ManualRevisedFebruary 2012

TB Manual
February 2012 | For professionals to help manage tuberculosis

2
TABLE OF CONTENTS
INTRODUCTION
PURPOSE OF THE MANUAL
ROLES & RESPONSIBILITIES
SECTION I: SCREENING FOR TUBERCULOSIS
7 Screening Programs for Populations at Risk
14 Screening & Diagnostic Tools
17 Tuberculin Skin Test (TST)
22 Radiology
25 Bacteriological Examination of Sputum
28 Flow Chart: TB Mycobacteriology
SECTION II: ACTIVE TUBERCULOSIS
30 Case Management & Active Case Finding
39 Flow Chart: Management of An Active Case of Tuberculosis
SECTION III: CONTACT INVESTIGATION
41 Goals of Contact Investigation
41 Roles & Responsibilities
42 Principles to Guide Contact Investigation
44 Assigning Priority for Investigation of Contacts
46 Conducting a Contact Investigation
48 Contact Examination Procedure
52 Contact Examination in Congregate Settings
SECTION IV: PREVENTION
56 Preventative Therapy
60 Rifampin Preventative Treatment
62 Medication Reordering Instructions for Latent TB Infection
SECTION V: APPENDIX
66 Appendix A: Glossary
71 Appendix B: Basic Facts about Tuberculosis
74 Appendix C: Medications
91 Appendix D: Pediatric TB
95 Appendix E: TB Services for Aboriginal Communities
117 Appendix F: BCG Vaccine
119 Appendix G: Tumour Necrosis Factor
121 Appendix H: Atypical Mycobacteria
124 Appendix I: TB & HIV
126 Appendix J: Multiple Drug Resistent TB
128 Appendix K: Directly Observed Therapy
131 Appendix L: Interim Guidelines for use of IGRA Studies
132 Appendix M: Molecular (Diagnostic Tools)
134 Appendix N: Immigration
137 Appendix O: Tuberculosis & Chronic Renal Failure
139 Appendix P: Sputum Induction
141 Appendix Q: Forms
3
4
5
6
29
40
55
65
3
INTRODUCTION
This manual was developed by the physicians and nurses at TB Control to meet
the needs of those professionals throughout the province responsible for managing
tuberculosis. It refects the changing policies and practices at TB Control which in
turn are based on current research fndings and new technology. The 6th Edition
of the Canadian Tuberculosis Standards has provided the foundation on which the
manual was organized. While there have not been dramatic shifts in management
principles of tuberculosis there are some important changes that have taken place.
The intention was to create a manual that is user-friendly, clear and concise and
one that will approximate any expectations that users of the manual may have.
As a Provincial Manual it provides direction to health professionals working in
a variety of settings. As such it cannot possibly meet all the needs of each health
unit and their community. It will be incumbent upon the health centres to work
with TB Control in developing strategies to confront the challenges they are
facing, whether it is an outbreak setting or an isolated First Nations community.
It is our desire to have a manual that provides both direction and fexibility. As
tuberculosis information and practices are continually evolving an efort will be
made to provide timely updates to the manual and communicate these changes to
the feld accordingly. An important component of this guideline for best practice
in the area of tuberculosis control is comments from the users. Every efort will
be made to incorporate that feedback in our ongoing upgrading of the manual to
better service health professionals in BC.
4
PURPOSE OF THE MANUAL
Bill 23 2008: The Public Health Act, Communicable Disease Regulation; Part 3
(www.leg.bc.ca/38th4th/1st_read/gov23-1.htm#part3) requires that tuberculosis
(TB) be reported under schedule A. This tuberculosis manual is designed for the
use of staf designated under the Public Health Act to provide tuberculosis control
and surveillance.
The document is produced by the Division of TB Control at the BC Centre for
Disease Control (BCCDC), an agency of Provincial Health Services Authority
(PHSA), to act as a guide for nurses and doctors working in public health,
community health, and infection controlas well as a reference for students,
researchers, and primary care physicians.
The Division of TB Control is responsible for the establishment and maintenance
of policies, standards and procedures for the control of TB in British Columbia. The
Canadian Tuberculosis Standards 2007 are used as guidance and adapted to meet
the specifc needs within British Columbia.
The manual contains background information regarding the signifcant
aspects of tuberculosis, the policies, standards, and guidelines for the control
and surveillance of tuberculosis, as well as the supporting documentation and
data collection tools. This manual is meant to be used in conjunction with the
Canadian TB Standards (2007). Copies of the Canadian Tuberculosis Standards
are available by contacting the BC Lung Association at 604-731-LUNG (5864)
or 1-800-665-LUNG (5864) outside the Lower Mainland, or on line at
http://www.phac-aspc.gc.ca/tbpc-latb/pubs/tbstand07-eng.php
The manual is organized to guide the reader in TB screening methods for various
high risk populations, diagnosis and treatment of active TB cases, diagnosis
and treatment of latent TB, contact tracing, TB prevention and client education.
The appendices provide additional information, forms and resources for patient
teaching, as well as a glossary of defnitions frequently used in TB Control.
Recommendations for revisions may be directed to the Director of TB Control.

5
ROLES AND RESPONSIBILITIES
The responsibility for the control of communicable diseases, including TB, lies with
the Medical Health Of cer. The clinical care of an active case of tuberculosis is the
responsibility of the clients personal physician, frequently in consultation with the
physicians at TB Control and with the assistance of local public health nurses and
community health nurses working in Aboriginal communities.
TUBERCULOSIS CONTROL (TB CONTROL)
TB Control provides central coordination of management and control measures
for cases, contacts, and others at risk of developing tuberculosis. This includes the
control and provision of free medications for treatment of active disease and latent
infection. It also includes coordination of contact investigation, administration
of the provincial TB registry database, and reporting of cases nationally. TB
Control is committed to supporting regional health authorities and Aboriginal
communities in ensuring the provisions of the Bill 23 2008: Public Health Act
and communicable disease regulations are met.
PUBLIC HEALTH
Public and community health nurses play a central role in the delivery of the
TB program in BC. In collaboration with the primary care physician, MHO,
and TB Control they are actively involved in surveillance, contact investigation,
supervision of treatment of both active TB and latent TB infection within their
health regions. In most instances, they are the primary contact with clients
and consequently have a signifcant infuence on the outcome of the treatment
program. Information collected in the feld by public health should be relayed to
TB Control so client care is consistent, safe and epidemiological data can be used
for future program development.

6
SECTION I SCREENING FOR TUBERCULOSIS
Screening Programs for Populations at Risk | 7
Screening & Diagnostic Tools | 14
Tuberculin Skin Test (TST) | 17
Radiology | 22
Bacteriological Examination of Sputum | 25
7
SCREENING PROGRAMS FOR POPULATIONS AT RISK
TB Control recommends that certain groups of the population should be screened
based on relative risk factors. Specifc populations and programs selected for
screening are as follows:
Detox Centres and Residential Alcohol & Drug Treatment Programs
Adult Licensed Residential Community Care Facilities
Licensed Child Care Facilities
Correctional Facilities
Other Specific Populations (i.e. Health Care employees and Immigration
1) DETOX AND RESIDENTIAL TREATMENT CENTRES
The goal is to identify and treat individuals with active TB disease and prevent
transmission to a vulnerable population in group settings.
RATIONALE:
Detox facilities are often short stay settings. Thus, TB Control does not recommend
TB skin testing as it requires a reading 48 to 72 hours after initial planting and only
indicates infection as opposed to active disease. Chest X-rays (CXR), sputum collection
and symptom assessment are more valuable tools in ruling out active disease which is
the goal in screening for admission to detox and treatment centers.
TABLE 1.1: SCREENING FOR DETOX CENTRES AND RESIDENTIAL TREATMENT PROGRAMS
Clients Tuberculin Skin Test
(TST)
Chest X-ray (CXR) Symptom Inquiry Sputum collection
for AFB (3 samples)
Detox Centres
Following entry to
facility
NOtypically very
short stays and
difficult to locate
client following
departure
YES YES If abnormal CXR or
symptomatic:
Collect 1 specimen
immediately, then
2 additional on the
following 2 days
Residential Drug &
Alcohol Treatment
Programs
Complete prior to entry
to facility
YESunless
documentation of
previous positive TST
or history of active TB
disease (treated)
If TST is positive, or
history of positive
TST/active TB or
showing symptoms
of TB
YES If abnormal CXR,
symptomatic, or
unwilling to have
CXR: Collect 1
specimen immediately,
then 2 additional on
the following 2 days

Note: for employee screening, please refer to Public Service Guidelines page 9.

8
2) ADULT LICENSED RESIDENTIAL COMMUNITY CARE FACILITIES
All persons who are entering a care facility, or starting employment in such a
facility, should be screened for TB before admission by their private physician,
public health, or TB Control. Due to the challenges of screening for TB prior
to admission, a patient or employee may be screened post admission as
recommended below if they are not symptomatic. The Medical Health Officer
may make alternative policy decisions based on local disease incidence and
prevalence. The Tuberculosis Screening Program Form (HLTH 939) must be used
for the initial screening program. http://www.bccdc.ca/NR/rdonlyres/69DDB0EB-
CC6C-458C-8EEC-67C3899C6AD2/0/HLTH939_Feb2011.pdf
RATIONALE
To minimize the risk of spreading active TB disease as residents in care facilities
tend to remain for long periods of time in an environment which would pose a
risk to both the staff and the other residents. Compared to general hospitals, care
facilities tend to have reduced levels of medical surveillance. As many clients
have reduced mental alertness, it is important to screen the above group within
the suggested period of time. Preventing a case of TB from spreading within a
facility reduces the need for extensive contact tracing and keeps others healthy.
9
TABLE 1.2: SCREENING FOR ADULT LICENSED RESIDENTIAL COMMUNITY CARE FACILITIES *
Tuberculin Skin Test
(TST)
for AFB (3 samples)
Resident:
Complete prior to
admission or within
1 month of admission
if not symptomatic
YESonly for
residents less than
60 years of age and
previously skin test
negative or unknown
YESfor residents 60
years of age and older,
or symptomatic, or
have a positive TST or
persons who have risk
factors for TB
YES If abnormal CXR or
symptomatic:

Submit 3 sputa for AFB
New Employees:
Complete prior to
employment or within
2 weeks
YESunless
documentation
of previous positive
TST or history of
active TB disease or
if TST neg in last 6
months & no contact
with active case
YESif TST is positive
or symptoms of TB
symptomatic:

* All licensed group home screening should be based on contact tracing of active cases. Routine
screening, not required.
EXCLUSIONS FOR RESIDENTS:

Where there is dif culty arranging a chest radiograph at the time of
admission, the following are acceptable:
A normal chest radiograph completed within one year preceding admission
for asymptomatic clients.
EXCLUSIONS FOR EMPLOYEES:
Normal CXR in the past 6 months
Pregnant employees should have CXR following delivery. Contact TB Control if symptomatic
EXCLUSION FOR TUBERCULIN SKIN TEST (TST):
Previous TB
History of anaphylaxis or severe reaction to TST
Documented previous positive TST
10
3) LICENSED CHILD CARE FACILITIES
Routine screening of employees of licensed child care facilities is currently not
recommended except in Aboriginal communities as identifed by TB Control.
RATIONALE
A review of our cases shows that no child had been infected as a result of exposure
to a child care worker in non-Aboriginal communities in BC within the last ten
years. Screening of child care employees is logistically dif cult and can be costly
due to the large turnover of employees.
The only exceptions to these recommendations are Aboriginal child care facilities
which will continue to require screening at this time. (See Appendix E)
NOTE: These recommendations can be changed at the discretion of the local Medical
Health Officer depending on local circumstances.
4) CORRECTIONAL FACILITIES
Individuals in the correctional setting are at relatively high-risk of being infected
with tuberculosis or having active disease resulting in the potential for outbreaks
in these institutions.
FEDERAL CORRECTIONAL FACILITIES
In 1994, tuberculin skin test was replaced with two-step testing. Individuals with
a positive tuberculin or symptoms are referred for chest x-ray and a medical
evaluation.
PROVINCIAL CORRECTIONAL FACILITIES
There are a high number of admissions per year, with the vast majority of inmates
staying for weeks or months at a time. Inmates are assessed upon admission. No
routine tuberculin skin testing is done on asymptomatic inmates. Symptomatic
inmates are referred for medical assessment and TB workup (TST, sputum and
chest x-ray). Any inmate with a positive skin test should have a chest x-ray and if
symptomatic, three sputum specimens should be submitted for AFB.

Correction facility staf should have a baseline TST performed when hired. Further
testing should only be done in response to an exposure to an active case.
11
TABLE 1.3: SCREENING FOR FEDERAL AND PROVINCIAL CORRECTIONAL FACILITIES
(TST)
for AFB (3 samples)
Federal Corrections:
Inmates
YESonce for new
admissions
Repeat annually for
inmates with negative
TST
YESfor inmates
with a positive TST or
refusing a TST
YES * If abnormal CXR or
symptomatic:

Federal Corrections:
Staf f
YESbaseline upon
employment and
annually if negative
TST
Baseline if previous
positive TST or active
TB
symptomatic:
Provincial
Corrections:
Inmates
Not routineonly if
client is symptomatic
or at risk for TB (i.e.
HIV positive)
Not routine
All symptomatic
inmates
YES * If abnormal CXR or
symptomatic:
Provincial
Corrections:
Staf f
YESbaseline TST,
unless documented
exclusions
Baseline if previous
positive TST or history
of active TB
YES
* Symptomatic inmates isolated until TB ruled out

5) OTHER SPECIFIC POPULATIONS
Health Care and Public Service Employees
Volunteers
Post Secondary Institutions
Immigration Surveillance
High Risk Individuals
12
HEALTH CARE & PUBLIC SERVICE EMPLOYEES

TB Control recommends that all employees be screened for TB at the time of
hiring. The establishment of baseline data for individuals in the above groups
determines who has been infected with the tubercle bacillus and who has not.
Institutions with the classifcation of medium to high risk of exposure for staf may
decide to implement routine TB screening as an adjunct or substitution for contact
investigation. Once the baseline has been established, contact screening may be
more easily undertaken when necessary.
Local conditions may be such that the Medical Health Of cer and TB Control
jointly make alternate policy decisions.
It is the responsibility of institution to implement.
TABLE 1.4: SCREENING FOR HEALTH CARE AND PUBLIC SERVICE EMPLOYEES
(TST)
for AFB (3 samples)
Health Care
Employees
(Hospitals):
Responsibility
of institution to
implement
YESbaseline upon
employment and
annually if negative
TST
Repeat TST based on
exposure to active
TB or in accordance
with facility Infection
Control Committee
recommendations
based on level of risk
for exposure.
YES if baseline
TST positive at
time of hiring, or
symptomatic
Repeat CXR if exposed
to active TB
symptomatic:

Public Service
Employees:
Examples include:
Community/Public
Health nurses, home
care nurses, street
nurses, police, fire-
fighters
YESbaseline TST
upon employment
Repeat TST based on
exposure to active TB
YESif TST is positive
or showing symptoms
of TB
Repeat CXR if exposed
to active TB
symptomatic:

13
VOLUNTEERS
The need for testing is determined locally and on an individual basis.
Volunteers working with high risk populations (see page 16) should follow the
same recommendations as for public service employees.
POST-SECONDARY INSTITUTIONS
Currently it is not our policy in British Columbia to screen post-secondary students
for tuberculosis. Exceptions to this general policy should only be made at the
discretion of the local Medical Health Of cer in consultation with TB Control.
An exception to this policy is for students in health care who require baseline TB
screening prior to direct patient care.
IMMIGRATION SURVEILLANCE

Health and Welfare Canada screens all persons applying for immigration to
Canada. Immigrants who have a history of previous tuberculosis, or who have
evidence on chest radiograph of inactive tuberculosis, are referred to TB Control
upon arrival in Canada. These persons have signed a form that states they will
comply with surveillance requirements and report to TB Control for assessment.
Upon receiving notifcation from Health and Citizenship Canada, TB Control will
send notifcation (see Appendix N page 136) to the health unit (HU) in which
this person resides requesting:

A health history (form 939)
Chest radiograph
Three sputum specimens.
Health Units (HU) will locate the person(s) and advise them of TB Controls request
and will arrange for chest radiograph and the collection of the specimens to be
sent to TB Control. (See Appendix N)
If the individual is asymptomatic and does not have health coverage, the chest
x-ray (CXR) can be delayed until they are eligible for health coverage (usually
within three months). If an immigrant is symptomatic requiring a CXR before
three months they will be requested to cover the cost. In the event there is fnancial
hardship TB Control will cover the cost of the CXR for those who are symptomatic.

14
TABLE 1.5: SCREENING FOR POST-LANDING IMMIGRATION SURVEILLANCE
(TST)
for AFB (3 samples)
Post-landing
surveillance
NO YES YES YES
HIGH RISK INDIVIDUALS
The following groups require special considerations for screening relating to
their individual risk factors. TB Control recommends TST, symptom inquiry, and
baseline chest x-ray for the following individuals:

HIV positive
Organ Transplant
Dialysis
Prior to starting Tumour Necrosis Factor (TNF) inhibitor (Appendix G)
Street involved including; alcohol and/or substance users
Follow-up screening based on the exposure to active TB or at the
discretion of local healthcare providers

SCREENING AND DIAGNOSTIC TOOLS
ASSESSMENT COMPLETING HLTH 939 FORM
Proper assessment of an individual and documentation of the assessment provides
important clinical information which assists the clinicians at TB Control to
make a diagnosis and/or recommendations. The HLTH 939 form is a guideline to
completing the assessment and includes the following points:

Demographics
History
Contact information
Risk factors for developing active TB
Symptoms of active TB
The public health nurse (PHN) and community health nurse (CHN) must ensure
the following information is collected and conveyed to TB Control by way of a
Health (HLTH) 939 form for each client screened for TB (See forms in Appendix Q).

http://www.bccdc.ca/NR/rdonlyres/69DDB0EB-CC6C-458C-8EEC-67C3899C6AD2/0/
HLTH939_Feb2011.pdf
15
TST
Indication for screening
Contraindication
Tuberculin Skin Test (TST)to identify individuals who have been
infected by tubercle bacilli (see Appendix Q Decision Support
Tools TST)
Chest x-ray if history, symptoms, and/or TST indicate necessity
3 sputum specimens submitted for AFB smear and culture if
symptom inquiry, chest radiograph and/or TST indicate necessity
DEMOGRAPHICS

Obtain personal informatione.g. name, date of birth, sex, address, phone
number, physicians name and address, and Personal Health Number (PHN)
Ethnic origin
Aboriginal statuslives on or off reserve; community & health centre
Country or Canadian province of birthif patient is from outside of Canada,
must indicate date of arrival in Canada
HISTORY
Prior exposure to tuberculosis
Previous active TB and treatment
Previous preventive treatment
Previous tuberculin tests, if any, provide results
Previous BCG, presence of BCG scar
Travel to countries which have high incidences of TB (length of travel)
CONTACT INFORMATION
TB number of source case (if TB number not yet assigned may use PHN)
Date of contact, length of contact, type of contact, location of contact
Indicate if TST baseline or 8 weeks post contact
TYPE OF CONTACT:
Type 1Household or share the same air space for more than 4 hrs/wk
Type 2Non-household or share the same air space for 24 hrs/wk
Type 3Casual or share the same air space for less than 2 hrs/wk
NOTE: Further detailed information about contact tracing will be discussed in Section IV: Contact Tracing

16
RISK FACTORS FOR DEVELOPING ACTIVE TB
INCREASED RISK
Treatment with glucocorticoids or any other immunosuppressive agent
TNF inhibitors (see Appendix G)
Diabetes
Underweight (less than 90% ideal body weight or BMI less than 20)
Young age when infected (equal to or less than 5)
IV drug use/ crack cocaine
Homelessness
HIGH RISK
HIV/AIDS
Transplantation (related to immunosuppressant therapy)
Chronic renal failure requiring hemodialysis
Carcinoma of head & neck
Recent TB infection ( TB contact within 2 years)
TB contact within 2 years
Silicosis
SYMPTOMS OF ACTIVE TUBERCULOSIS

Cough, and/or sputum production greater than 3 weeks (Collect 3 sputum on 3 consecutive days)
Sputum production
Blood in sputum (hemoptysis)
Night sweats
Fever
Fatigue
Weight loss
Loss of appetite
Chest pain
Other symptoms will depend on the site of disease
17
TUBERCULIN SKIN TEST (TST)
PURPOSE: To determine whether an individual has been infected
with the tubercle bacillus as evidenced by a positive tuberculin skin test.

The tuberculin skin test (TST) is the main test used to diagnose
latent tuberculosis infection (LTBI). This test consists of an
intradermal injection of 0.1 ml of purifed protein derived from
Mycobacterium tuberculosis bacteria. In a person with normal
immunity to these tuberculin antigens, a cell-mediated, delayed
type hypersensitivity reaction will occur within 4872 hours. The
reaction will cause localized swelling and will be manifest as
induration of the skin at the injection site. It requires 3 to 8 weeks
after an exposure for the body to mount a response and for the test
to turn positive.
A tuberculin skin test is not diagnostic of active tuberculosis
disease. Other diagnostic tools (i.e. sputum for AFB, chest x-ray,
symptom inquiry) are the principle means of screening for active
TB disease. A negative TST does not exclude a diagnosis of active
tuberculosis. If symptomatic, collect 3 sputum specimens for
mycobacteriology, send for chest x-ray, and call TB Control for
further advice.
INDICATIONS FOR TST ADMINISTRATION
Contacts of a patient with a recent diagnosis of active infectious TB
Household, or close contacts of a patient diagnosed with extra-pulmonary TB
Reverse contacts of a child diagnosed with active TB
Screening individuals prior to starting tumour necrosis factor (TNF) inhibitors.
Screening programs for select groups of persons judged to be at risk
i.e. kidney dialysis patients
HIV positive individuals and individuals at high risk for HIV infection
i.e. Injection Drug Users (IDU). TST results may not be reliable in HIV positive
individuals with low CD4 counts (less than 200).
International travelers who will be residing in countries where tuberculosis is
endemic. These travelers should have a base-line TST before leaving Canada and
a TST on return to Canada. A two-step TST is an option in this situation at base-
line testing.
Travellers returning from visits to endemic areas
Mass screening to determine community prevalence of infection (only applies to
identified Aboriginal Communities See Appendix E)
Specifc populations at risk, for example: Health Care Employees (see Screening section)
Individuals with signs and/or symptoms of active tuberculosis, remembering that a
negative TST does not rule out TB
NOTE: Reliance should not be
placed on a previous TST that
was not documented unless
the person can give you a
clear description of extensive
swelling, especially with
blistering.
18
CONTRAINDICATIONS
Persons who have had an anaphylactic response or severe reaction to a previous
TST using Tubersol, a similar product or components of Tubersol.
Persons who have a documented history of a previous positive reaction to
tuberculin testing.
Persons who have documentation of previous active tuberculosis.
Persons with major viral infections or live-virus vaccinations in the past 4 weeks
(to avoid false negative reactions).
Individuals with severe burns or eczema at skin testing sites.
NOTE:
A history of a Bacille Calmette-Guerin (BCG) vaccine is not a
contraindication for a TST.
Pregnancy is not a contraindication for a TST.
TST may be given on the same day as MMR and/or Varicella, and
Yellow Fever vaccine otherwise wait for at least 4 weeks.
19
ADMINISTRATION OF TUBERCULIN SKIN TEST
Tuberculin skin testing is standardized by using Sanof Pasteur Tubersol bio-
equivalent to 5 TU (0.1 ml of tuberculin) of purifed protein derivative (PPD),
which is supplied by the pharmacy at BC Centre for Disease Control.
Tubersol should be used as soon as it is drawn up in the syringe as the tendency of
tuberculin to adhere to plastic surfaces causes marked reduction of the strength of the
solution. Sanof Pasteur, maker of the PPD, recommends that the tuberculin be left
drawn up in the syringe for a maximum of 20 minutes. Tubersol should be stored in
a refrigerator (28 C) and can be adversely afected by exposure to light.
PREPARATION
Ensure all equipment is readily available, including sharps container
and anaphylaxis kit.
Seat the client comfortably and explain the procedure. Ensure that
the client is aware that they must return in 4872 hours for reading.
Self-reading of skin test results by the client is not acceptable.
Wash your hands.
Use a tuberculin syringe with a 26 to 27 gauge needle
INJECTION PROCESS
Cleanse the skin with isopropyl alcohol (unless allergic) and allow to dry.
The skin of the forearm should be held taut with one hand.
Administer test intradermally on the anterior forearm, 2 to 4 inches
below the elbow (see picture below).
The syringe should be held at a 5 degree angle, with bevel up.
Insert the needle just underneath the first layer of skin and slowly
inject 0.1ml of tuberculin. You should be able to see the tip of the
needle underneath the skin and feel resistance when you inject.
A wheal or bleb 6 to 10 mm in diameter should appear.
If an elevated wheal does not appear, repeat the skin test 20 mm
below the original site or the other arm.
Band-aids are not recommended, but if used should be removed
30 minutes after the tuberculin is administered.
Instruct client to remain in the clinic area for 15 minutes after the
injection to ensure they have not had an allergic reaction.
20
READING THE TUBERCULIN SKIN TEST
A tuberculin skin test should be read 48 to 72 hours after administration by a
health care professional trained in this skill. Self-reading of skin test results by the
client is not acceptable.
Results should be recorded in millimetres (mm), not as positive
or negative.
Negative skin test reactions show no mark or a small bruise around
the injection site. Some skin test reactions will show an area of
erythema (redness) around the injection site, but no induration can
be palpable at the site. The reaction should be recorded as 0mm.
Large skin test reactions will show an inner indurated area, which
may be blistered, surrounded by erythema. Only the inner
indurated area should be measured. The presence of blistering at
the site should also be recorded.
READING PROCESS
Support the forearm on a firm surface
Mark the borders of induration by moving your finger or the tip
of a pen at a 45 degree angle transversely across the arm towards
the site of injection until there is resistance indicating an edge if
one present. Mark that edge.
Repeat on the other side
Measure the distance between the two marks with a calliper ruler
if available if not a flexible ruler can be used.
INTERPRETATION OF THE TUBERCULIN SKIN TEST
The interpretation of the tuberculin skin test depends on the reason
for testing and can rely heavily on data provided on the HLTH 939.
5 mm or greater skin test reaction is considered positive for the
following groups:
Contacts of an active case of TB
Immuno-compromised individuals
Individuals with HIV infection
Individuals with chest x-rays compatible with
previous TB disease
IV drug users
10 mm or greater skin test reaction is considered positive for all other groups
Individuals with a positive skin test reaction should be referred for a
chest x-ray. The Tuberculosis Screening Program form, (HLTH 939)
when completed which acts as the chest x-ray requisition form.

NOTE: A Personal Health
Number (PHN) is required
for all TB chest x-rays as
of April 2009.
21
UNINTENDED OUTCOMES

ANAPHYLAXIS is very rare but is possible. Epinephrine Hydrochloride Solution
(1:1000) must be readily available when administering a tuberculin skin test.
Follow the BC Centre for Disease Control Immunization Programs Protocol for
Emergency Treatment for Anaphylaxis. (See http://www.bccdc.ca/dis-cond/comm-
manual/CDManualChap2.htm, Immunization Manual Section 5)
Document in clients record
Inform TB Control and local MHO; have vial lot # & do not throw out.
SEVERE REACTION is one with excessive swelling, pain or discomfort, or progression
to the stage of vesiculation and sloughing of tissue. Severe reactions sometimes are
associated with infammation of the lymphatics draining the area (red streaks in
the arm) and with soreness or swelling of the glands in the axilla. This is almost
always a sensitivity reaction and should not be confused with secondary infection.
Apply sterile, dry dressing to any open or sloughing area. (Cortisone ointment has
not been found to be helpful). Reassure client about early resolution though some
red-purple discolouration may persist for several weeks. Certain skin types may scar.
At the discretion of the public health nurse, refer person to personal physician.
Severe reaction should be documented on the HLTH 939 form and in clients record.

Pain, itchiness, discomfort at the site may occur, and should be treated with the use
of cold compresses. Benadryl can be efective in reducing the efect of the side-efects.
TWO-STEP TUBERCULIN SKIN TESTING
The two-step Tuberculin Skin Test identifes individuals who had been infected
in the past, but may now have a decreased sensitivity to the TST. It enables one
to distinguish between what could be a booster response and a true conversion
from a recent contact. It is useful as a baseline for individuals working in high
risk settings who will continue to be followed by TSTs. It can be an option in other
settings such as HIV positive in high prevalence communities if resources are
available. It should not be used for screening of contacts and need only be done
once.
Procedure for administering a 2-step skin test involves completing the initial TST
and if the TST is negative, a second TST is administered one to four weeks later.
The second one should be administered on the opposite forearm or 5 cm below
the previous site. The same techniques and principals of skin testing apply to the
2-step skin test.
Due to staf ng, resources and practicality, 2-step testing is not generally
recommended by TB Control. Travellers, those working in corrections, and health
care workers are individuals who might beneft from 2-step skin testing when
resources permit.
22
RADIOLOGY
PURPOSE: To evaluate individuals with a positive TST or symptoms
compatible of TB disease.
Although the chest x-ray is a widely used diagnostic tool, the
fndings are not specifc for TB and can be confused with other
diagnoses such as pneumonia or lung cancer. Although treatment
may be initiated based on chest x-ray fndings alone, sputum
collection remains mandatory to provide defnitive proof of disease.
The chest x-ray is the only way to follow individuals who have had
previous abnormal chest x-rays suggestive of old TB disease or latent
infection to determine if there are new radiological changes.
The Tuberculosis Screening Form (HLTH 939) provides a guideline to
assess a client for a TB screening chest x-ray.

INDICATIONS FOR CHEST RADIOGRAPH
Tuberculin skin test positive (10 mm or greater) on general screening
Contact of an active case of tuberculosis who has a skin test equal to or greater than
5 mm
Children under 5 years of age who are close contacts of an active case of infectious
TB
HIV positive individual who has a tuberculin skin test equal to or greater than
5 mm (note: HIV positive clients should have a base-line chest x-ray)
Immunocompromised individual who has a tuberculin skin test equal to or greater
than 5 mm
Immunocompromised individuals, or IDUs, who are contacts of an active case
regardless of TST results.
Immigration medical surveillance requirements (directed by TB Control)
Suspect case with signs and/or symptoms of active tuberculosis
Individuals requiring TB screening who have had previous documented positive
tuberculin skin test
Individuals requiring TB screening who have had documented tuberculosis
Prior to starting preventative therapy for latent TB infection
Admissions at or over the age of 60 years to Adult Licensed Residential Community
Care Facilities (preferably within one month of admission)
Urgent admission to Detox/Drug & Alcohol Treatment Programs
Those individuals starting TNF inhibitors
Others at the discretion of the Division of Tuberculosis Control
23
A chest x-ray that has been done within the last six months should satisfy any
of the above indications for a chest x-ray. There are some exceptions to this rule
which include:
Contacts of active TB
Individuals with signs and/or symptoms of active TB
Individuals with high/increased risk factors for developing active TB
and are TST or IGRA positive

NOTE: Contact TB Control for advice for these individuals.
A TB screening chest x-ray should not be done in place of a tuberculin skin test
unless there is a contraindication to planting a skin test. Any exceptions should be
discussed with TB Control.
CONTRAINDICATIONS
Pregnant women during the frst two trimesters should avoid chest x-rays if
possible. In these situations, tuberculin and sputum testing may be utilized for the
diagnosis of tuberculosis. If chest x-rays are essential, appropriate shielding should
be used. Consult with TB Control.
X-RAY PROCESS
Efective April 1, 2009 MSP has assumed the fnancial responsibility for the cost of
TB CXRs. In areas not serviced by stationary TB Clinics, the revised HLTH 939 form
still acts as the requisition enabling the individual to obtain a CXR at a private
radiology clinic or hospital. The billing number 99996 is printed on the HLTH 939
form and there is space for the individuals PHN. Steps of the CXR process include:
STEP 1: The health unit flls out the HLTH 939 and faxes a copy to TB Control.
STEP 2: Individual takes white copy to a local radiology department and can keep
the pink copy for their own records.
STEP 3: If the chest x-ray is normal, the radiology department is instructed to send/
fax copy of the report and HLTH 939 forms to TB Control and the family physician,
so we get 2 copies. If the screening is done for detox, long term care facility, school
or employment and the report is normal, then the individual may contact their
family physician for results.
STEP 4: If the CXR is non-digital and abnormal the radiology department is
instructed to send the flm, HLTH 939, and report to TB Control. If the CXR is
digital and abnormal the radiology dept. will fax the report and HLTH 939 to TB
Control. TB Control will then contact them when they need to have the chest x-ray
transferred to 'the grid' to be read.
24
STEP 5: If TB Control does not receive the CXR and/or report within three weeks of receiving
the initial HLTH 939, TB Control will fax the HLTH 939 form back to the HU for appropriate
follow-up.
STEP 6: The respirologist at TB Control review the CXR, sputum results, and HLTH 939 form
with recommendations made and sent to the HU and private physician.
Depending on a number of variables the turn around time from when TB Control
receives an x-ray to when a report is sent out is unpredictable. Sending the CXR by
mail as opposed to putting it up on the grid delays the process. All reports must
be dictated, typed and then validated by the physician at TB Control. It can then
take up to 2 weeks before a consult report is sent out. If you have not received any
information after that time please contact TB Control.
For those individuals with signifcant symptoms and if urgency of diagnosis is
required, please contact the Field Operations/TBSAC nurse to expedite the process.
For those needing to know at what stage the chest x-ray process is, they can contact
the appropriate radiology clerk at TB Control. (See Organizational Chart).
25
BACTERIOLOGICAL EXAMINATION OF SPUTUM
Bacteriological examination of sputum is the only diagnostic tool that
provides defnitive proof a client sufers from active pulmonary tuberculosis
and is considered the "gold standard" for the diagnosis of TB disease. Without
bacteriological confrmation, drug sensitivities cannot be obtained making it
dif cult to select an appropriate drug regime.
INDICATIONS FOR SPUTUM COLLECTION

Any client with a chronic productive cough (greater than 3 weeks) or other
symptoms compatible with active tuberculosis
Post-Landing Immigration Surveillance clients
Any client with a positive TST and symptoms and/or abnormal CXR
HIV positive clients with a positive TST and/or symptoms
Any household contact with a positive TST and/or are symptomatic
(consult with TB Control)
For high risk clients who are unlikely to return their sputum containers, on-the-
spot sputum collection is an appropriate strategy. For clients unable to produce a
sputum sample, please refer client to a centre that carries out sputum induction.
(See Appendix P)
SPUTUM COLLECTION
CLINICAL PRACTICE STANDARDS
Containers and requisitions are available from the Provincial Laboratory;
Mycobacteriology requisition: http://www.bccdc.ca/NR/rdonlyres/BD6A7EAC-
8603-482A-9225-FB9D8939657A/0/MycobacteriologyandTBRequisitionForm.pdf
Container requisition: http://www.bccdc.ca/NR/rdonlyres/9CDC4B7D-6587-
4A17-ACEE-B6344FCA3285/0/RequisitionforSpecimenContainersSputumBottles.
pdf
Label containers with the clients name and complete the requisitions. Containers
without labels are discarded.
Please ensure all sputum specimen requisitions for AFB are also sent (ccd) to
TB Control.

26
Instructions to the client for obtaining sputum specimens should include:
Obtaining specimen in the morning upon rising (before eating)
Taking a deep breath and cough to raise sputum from the lungs
(mucous or saliva from the mouth is not useful)
Using a hot fluid drink to help stimulate sputum production if there
is difficulty in obtaining sputum
Collect the sputum specimen in the bottle supplied, ensuring the lid
is tightly secured. Place the bottle in the ziplock bag provided and
ensure the bag is filled with absorbent material, e.g. cotton balls or
tissue
Obtain sputum samples on 3 consecutive mornings
Keep sputum samples in the refrigerator and return them as soon as
possible to the health centre or local public health unit for delivery
to the Provincial Laboratory
The routine cooler and courier system may be utilized for sending
these specimens to the Provincial Laboratory
The specimens should not be sent during weekends or statutory
holidays
In order to avoid remaining for too long a period in an overheated
post office, sputum samples should be sent to the following
laboratory complying with transport of dangerous goods
regulations:
SPUTUM REPORTING
SMEAR
Results are reported within 24 hours after specimen is received at the laboratory.
They are not processed on the weekend and therefore specimens received on Friday
afternoon will be processed the following Monday morning.
POSITIVE SMEARAcid fast bacilli seen. This may indicate Non-
tuberculosis Mycobacterium (NTM). The majority of positive
smears in BC are NTM. Positive smears undergo PCR testing daily
Monday to Friday.
NEGATIVE SMEARNo acid fast bacilli seen. This does not rule out
active TB, but the likelihood the client has infectious TB is reduced.
Specimen is then cultured but not probed at this point.
Provincial Laboratory
BC Centre For Disease Control
655 W 12TH Avenue
Vancouver, BC, V5Z 4R4
27
CULTURE
Cultures are incubated in both liquid and solid media for up to 8 weeks. Both
positive and negative smears are cultured.

POSITIVE CULTUREGrowth of a mycobacterium. This may indicate
M. tuberculosis or a Non-tuberculosis mycobacterium (NTM).
Positive cultures will be probed once on either Tuesday or Thursday.

NEGATIVE CULTURENo growth on culture medium.
NOTE: Probes are tests to differentiate Mycobacterium tuberculosis from Non-tuberculosis
Mycobacterium (NTM) such as Mycobacterium avium (MAC) that do not cause infectious
tuberculosis.
SENSITIVITIES

One to two weeks after the culture grows, the sensitivity results will be available
through the provincial lab. The report will indicate which drugs the organism is
sensitive or resistant to and can infuence drug selection. The following drugs are
initially tested: Isoniazid, Rifampin, Ethambutol and Streptomycin. If resistance is
found to either Isoniazid or Rifampin, Pyrazinamide will be tested. If resistance
is found to both Isoniazid and Rifampin, second line drug sensitivities will
automatically be tested. Once the physician at TB Control has seen the results of
the sensitivities, prescription adjustments are made as needed and the appropriate
health care providers are informed.
NOTE: For information on Genotyping please see Appendix M
28
TB MYCOBACTERIOLOGY
RESPIROLOGY SPECIMEN (SPUTUM/BRONCHOSCOPY)
AFB SMEAR
Processed within 24 hours
CULTURE for MYCOBACTERIUM
Incubation for up to 8 weeks
(Growth usually is between 36 weeks)
Due to issues of
reliabiity, not routinely
performed on
non-respiratory
specimens
Positive growth of
Mycobacteria to be
identifed
(Culture)
Negative, no growth
Approx. 15% of TB
cases in Canada were
culture negative
POSITIVE
SMEAR
NEGATIVE
SMEAR
PCR testing
POSITIVE
CULTURE
MTB Complex
PROBE RESULTS
Non-tuberculosis
Mycobacterium (NTM)
PROBE RESULTS
ACCUPROBE
Results take 23 weeks after
a positive culture
DRUG SENSITIVITY TESTING
NEGATIVE
CULTURE
M. TB
complex
NTM
29
SECTION II ACTIVE TUBERCULOSIS
Case Management & Active Case Finding | 30
Flowchart: Management of An Active Case of Tuberculosis | 39
30
CASE MANAGEMENT / ACTIVE CASE FINDING
DIAGNOSIS OF TB
Tuberculosis is a communicable disease caused by the bacteria Mycobacterium
tuberculosis. Humans are its primary host and it may reside anywhere in the body
although it is primarily a pulmonary disease. TB is a reportable disease under the
Health Act (see Appendix B).
A diagnosis of active tuberculosis can be made when the following criteria can be
established:

A positive culture growing Mycobacterium tuberculosis complex. These
specimens can come from a variety of sources, including sputum, pleural
fluid, and urine. A positive PCR result predicts a positive culture for M. TB
In the absence of a positive culture there are a number of indicators
which can lead to a diagnosis of tuberculosis.
Abnormal radiological evidence consistent with active
tuberculosis. Abnormal chest x-rays, intravenous pyelogram
(IVP), and CT scans of chest and joints are useful tools in
arriving at a diagnosis.
Pathology indicating caseating granulomatous disease. Any suspect tissue
that is accessible to biopsy may be employed pleural, skin, lymph nodes,
and kidney biopsies. (See Appendix B).
Clinical symptoms consistent with actie tuberculosis - cough, night sweats,
fever, weight loss, hemoptysis, chest pain, fatigue, decreased appetite.

While the responsibility for the control of communicable diseases lies with the
Medical Health Of cer, the clinical care of an active case of tuberculosis is
the responsibility of the clients personal physician, often in consultation with
the physicians at TB Control and in collaboration with the local health units/
community health centres. Treatment is carried out based on the policies and
standards recommended by TB Control, who also supply the medication free of
charge.
NOTIFICATION
Upon notifcation of an active case of tuberculosis, TB Control will notify the
physician and the public health nurse. In consultation with a health care provider,
the client will be informed of the diagnosis. If the physician is unavailable it will
be the responsibility of the nurse to inform the client. If the client has no family
physician it will be incumbent upon the nurse to assist the client to fnd one who
will take responsibility for care.
31
ASSESSMENT/ INFORMATION GATHERING
After client has been informed of diagnosis it will be necessary to gather all
relevant medical information to determine the most efective treatment plan.
Included in this should be:
Clients drug allergies and weight.
An assessment of the clients social environment and those elements
which will affect issues of adherence and ability to self-isolate.
The Request for Information Form provided by TB Control should be flled
out and returned. This is information required by Health Canada.
Obtaining chest x-rays, lab work, medical consultations and
forwarding them to TB Control will be the responsibility of the
Public Health Nurse and/or Community Health Nurse. (Please refer
to Baseline Monitoring page 37).
Nurse to have patient sign an Access to Pharmanet Form which can
be downloaded off the website.
Included in the initial assessment should be a discussion of the
importance of contact tracing in reducing transmission and begin
collecting names for contact tracing. Please refer to section on
Contact Investigation.
EDUCATION
The PHN/CHN will meet with the client and family to assess their needs and
provide education regarding TB disease and treatment of it. Client needs to be
informed of common side efects of the medications, such as:
Orange urine, feces, sweat, tears from Rifampin
Peripheral neuropathy from Isoniazid
Rashes
Hepatotoxic symptoms such as nausea and vomiting, abdominal
pain and yellow eyes or yellowing of the skin.
NOTE: For a more comprehensive list of side-efects refer to medication list in Appendix C.
Education will be necessary for the duration of treatment and ongoing assessment
is important. When available, written educational material should be given to
the client (see BCCDC website: http://www.bccdc.ca/dis-cond/a-z/_t/Tuberculosis/
educmat/default.htm).

32
SELF-ISOLATION
Self-isolation at home is required if a diagnosis of pulmonary TB is made based on
smear positive or culture positive respiratory specimens.
Negative smear and Positive culture: requires self-isolation for at least 2 weeks
Positive smear and Positive culture: requires self-isolation for at least 2 weeks
(after the initiation of 1st line TB treatment) and 3 consecutive negative sputum
smears
There are a number of steps that can be taken to reduce transmission:
restrict public activities
no public transportation
restrict visitors to home
wear mask to all medical and lab appointments; surgical mask is
sufficient
care givers wear N95 protective masks
respiratory hygiene (cover mouth when coughing, spit into tissue,
tissue into garbage)
When the client is unable to efectively self-isolate based on the nurses assessment
then hospitalization is the preferred option. This decision should include the
family physician, the client and the PHN/CHN. The MHO and TB Control should
be consulted if any problems arise around self-isolation and/or hospitalization.
Self isolation can be a very dif cult time for both the patient and their family.
Let the client know of things they can dosuch as get out for walks for fresh
air. Encouragement, guidance, and re-enforcement are often needed during the
"isolation"period.
TREATMENT
Goals of treatment are to cure individual patients and minimize transmission
to other persons. Treatment is divided into two phases. The initial phase is the
intensive phase (three or four drugs given) and aims to quickly reduce the number
of rapidly dividing bacteria resulting in:
rapid reduction in symptoms
rapid reduction in infectiousness
reduction of the possibility of drug resistance
The second phase is referred to as the maintenance or continuation phase
(two or three drugs):
elimination of any persistent bacteria not destroyed in
the initial phase
reduction of the possibility for relapse
33
The importance of adherence cannot be overstated, especially in the intensive
phase to eliminate the potential for drug resistance. Exellent adherence limits the
chance of requiring a long and complicated, potentially 2nd line regimen and
promotes a successful outcome.
MEDICATIONS
All tuberculosis medications are provided without charge and distributed through
the BCCDC Provincial Pharmacy. A TB physician must generate the prescription. Any
prescriptions written by a physician in the community must be forwarded and reviewed
by TB Control in order to obtain medication. Local pharmacies will not provide the
medication. After a prescription is written a copy will be faxed to the health unit
and medications will be shipped. Most health units are supplied with starter units to
facilitate prompt initiation of therapy. Health units in many areas in the province are
also required to supply the local hospital with starter kits.
PHN/CHNs are required to administer medications to out-patients. If daily self-
administered treatment (SAT) is felt to be safe and appropriate the nurses will provide
the client with one month of medication only. If the client leaves the province or is
away on holiday, they will be provided with a maximum of two months medication to
take with them. If more medications are required the nurse should contact TB Control.
Clients who are on intermittent Directly Observed Therapy (DOT) should never be
given doses to self-administer because all doses must be directly observed by the PHN.
(See Appendix K).
The decision regarding SAT vs DOT is often recommended by the physicians at TB
Control in consultation with local healthcare providers.
34
TABLE 2.1: TREATMENT OF MYCOBACTERIAL DISEASE IN ADULTS FIRST LINE MEDICATIONS
ANTI-TUBERCULOSIS DRUG INFORMATION
Drug Major Adverse Reaction Monitoring Remarks
Isoniazid (INH)
10 mg/kg up to 300 mg
Twice weekly: 15 mg/kg PO
usually 900 mg
Hepatotoxicity
Hypersensitivity
Peripheral Neuropathy
Symptoms
AST/SGOT
Phenytoin (Dilantin)
toxicity
Pyridoxine (25-50 mg)
may be given to prevent
peripheral neuropathy.
With Disulfiram (Antabuse)
may lead to behaviour and
coordination disturbances.
Rifampin
Twice weekly: 10 mg/kg
usually 600 mg
Hepatotoxicity
Hypersensitivity
GI Upset
Thrombocytopenia
Symptoms
AST/SGOT
Baseline CBC (including
platelet count)
Decreases effectiveness of
the contraceptive pill.
Increases ANTICOAGULANT
drug requirement.
An orange-red
discolouration of sweat,
tears, (may stain soft
contact lenses), urine,
saliva, and feces.
Methadone dose may need
to be increased.
Rifabutin Rash, fatigue, fever & sore
throat.
Visual disturbances such as
eye pain.
Nausea, diarrhea, muscles
or joint pain
See Rifampin May cause tears, sweat,
urine & feces to be brown-
orange and use alternative
form of contraception if
using birth control pills.
Pyrazinamide
20-30 mg/kg up to 2 g
Hyperuricemia
Gastric irritation
Arthralgia
Hepatoxicity
Symptoms
AST/SGOT
Uric acid rise is
unpredictable and does not
require monitoring unless
history of gout.
Ethambutol
15 to 25 mg/kg
Retro bulbar neuritis
(rare at 15 mg/kg)
Hypersensitivity
Symptoms
Baseline visual acuity and
colour perception monthly by
medication provider.
If on long term ethambutol,
then pt should see an
ophthalmologist or an
optometrist when the above
not available
Client should report any
visual changes to physician
immediately.
35
TABLE 2.2: TREATMENT OF MYCOBACTERIAL DISEASE IN ADULTS SECOND LINE MEDICATIONS
Levaquin Rash, hives, or difficulty
breathing
Irregular heartbeats or
chest pain
Muscle, tendon or joint pain
Jaundice
Nausea, vomiting, diarrhea
Headache
Drowsiness or
lightheadedness
Symptoms Avoid taking the following
when taking Levaquin:
Antacids containing
Aluminum, Calcium
and/or Magnesium
Sucralfate (ulcer
medication)
Vitamins or mineral
supplements containing
Iron, Zinc or Calcium
Use caution when driving,
operating machinery or
performing hazardous
activity.
Avoid excessive exposure
to sunlight while taking
Levaquin.
Avoid pregnancy and
breastfeeding. If pregnancy
occurs, contact GP
Streptomycin
15 mg/kg up to 1 g
Twice weekly: 25 to 30 mg/
kg usually 1 g
8
th
nerve toxicity (especially
vestibular)
Hypersensitivity reactions
Paraesthesia, peri-oral (not
significant)
Mildly nephrotoxic
Symptoms
BUN
Creatinine
Hearing tests
Vestibular damage
(i.e. check balance and gait)
If pre-existing renal
impairment, monitor
closely.
Reduce dosage in older
clients
In children less than 14
years, after three weeks
daily therapy, reduce dose
or give intermittently.
Not to be used during
pregnancy
36
TABLE 2.2: TREATMENT OF MYCOBACTERIAL DISEASE IN ADULTS SECOND LINE MEDICATIONS
(CONT.)

Ethionamide
15 to 30 mg/kg up to 1 g PO
GI disturbance
Hepatotoxic
Hypersensitivity
Symptoms
AST/SGOT
Bacteriostatic to both
intracellular and
extracellular organisms.
Divided dose may help GI side
effects; has a metallic taste.
Avoid use during pregnancy.
Clofazamine (Lamprene)
100 mg daily
Discolouration of skin
tissue and body fluids (red-
coloured to brownish black)
and diminished sweating
and tear production.
Symptoms Bactericidal effect on
Mycobacterium bacilli.
Take with meals/food.
Capreomycin
for dosage see Appendix C
8
th
nerve damage
Nephrotoxic
Ototoxic
Symptoms
Vestibular function
Hearing tests
BUN
Creatinine
Bactericidal to both
intracellular and
extracellular organisms
and in cavities.
Use with caution in older
clients.
Rarely used if renal disease.
NOTE: See Appendix C for more comprehensive medication interaction table.
BASELINE MONITORING
The following baseline measurements are necessary to properly prescribe
appropriate treatment and allow for subsequent monitoring requirements during
treatment:
Weight in kilograms
HIV serology (consent, pre- & post-counselling required)
CBC with differential, liver enzymes (AST). For children under 16,
blood work is not required unless there are pre-existing medical
conditions (See pediatric appendix D)
Visual acuity and red/green color discrimination if Ethambutol is
prescribed (Schnelling chart or equivalent)
Assess clients knowledge of medication side efects and encourage them
to contact physician or nurse immediately with any adverse events
Hepatitis A, B & C serology: at the discretion of the family physician
37
ONGOING MONITORING
AST after two weeks of therapy, then monthly if AST is normal. In older patients
or those with underlying liver disease more frequent monitoring of bloodwork at
the discretion of the TB physician or GP may be necessary.
Assess patient monthly for signs of adverse effects: liver toxicity, peripheral
neuropathy, or rashes.
Visual acuity for those on Ethambutol. If Ethambutol is continued beyond
2 months, an assessment by an ophthalmologist is required; or optometrist if the
former is not available. Follow-up should be done according to recommendations
by the ophthalmologist.
For those on Streptomycin, a monthly assessment of hearing and vestibular
functioning should be undertaken.
Monitor for adherence (pill counts; blister packs)
For those clients who are smear positive, sputum should be collected every 2 weeks
until 3 negative smears have been reported (see sputum algorithm page 28).
Collect three sputums monthly until there are 3 negative cultures
Chest x-rays should be repeated every two months for pulmonary cases or as
otherwise recommended by TB Control.
For those clients with cavitary disease, repeat 3 sputums at the end of treatment
along with the exit chest x-ray.
Report to TB Control any adverse side effects or abnormal lab values.

ADHERENCE
For those clients on self-administered therapy the PHN/CHN will enquire as to
any doses missed. This should be recorded on the Medication Re-order Form
along with any pertinent information such as side efects or any dif culties with
treatment.
For those clients on Directly Observed Therapy the 'Record of Supervised TB
Medications' (http://www.bccdc.ca/NR/rdonlyres/EBFC0728-2B36-4412-B415-
75AF04CD1ECB/0/HLTH832_RevJuly2010.pdf) shall be flled out as indicated
in the legend. This serves not only as the adherence record, but also the reorder
form for more medication. A separate fax should be sent to report any other
information concerning treatment and issues. The appropriate TB Control nurse
consultant should be contacted by telephone with any urgent issues arising out
of treatment. If the TB nurse consultant is unavailable, contact the local GP with
concerns.
The initial reorder form should be flled out after the frst months medication is
provided so there is always one month supply available to ensure continuity of
treatment (See Appendix Q).
38

RECALCITRANT CLIENT

There may be clients who pose signifcant challenges in complying with TB
treatment. Every efort should be made to establish a respectful trusting
relationship and if obstacles arise, client-specifc strategies can be developed to
resolve them. This relationship building will help determine successful completion
of treatment. Discussions should include all relevant participants including the
family physician and TB Control. When a resolution is not possible, it is important
to keep the client informed and educated about future processes or decisions. The
PHN/CHN will be required to inform the MHO who will make an assessment as
to the risk for the community at large and will give direction accordingly. The
MHO and TB Control should be informed if there has been a two week period of
non-adherence. Ongoing eforts between the primary health care provider and the
client should be made to re-establish TB treatment.
39
MANAGEMENT OF AN ACTIVE CASE OF TUBERCULOSIS
PULMONARY TB NON-PULMONARY TB
- Clinical evaluation
- Sputum x 3 if productive cough
- Baseline CXR
- Smear for AFB or
- Culture for MTB
- Ensure 3 sputum collected
for baseline (3 separate days
if possible)
- 3 sputums Q 2 weeks until 3
consecutive negative smears
- Q monthly until 3
consecutive negative cultures
. A 2 month sputum collection
provides test of conversion
POSITIVE SPUTUM BASELINE SCREENING
- No isolation if Pulmonary TB
is excluded
- Monthly clinical assessment
of symptoms, improvement and
side efects of medications
- Radiological follow-up as
recommended by TB Control
FOLLOW-UP
ABNORMAL X-RAY
- Recommend DOT (Directly Observed Therapy)
- Requires prescription from TB Control
- Standard Regime: Isoniazid, Rifampin, Pyrazinamide, Ethambutol, Vit B6
MEDICATION
- Baseline: CBC, Diferential, AST
- AST at 2 weeks then:-
- Q monthly for the frst 3 months if normal followed by:
- Q 2 months for duration of treatment
- Abnormal values contact TB Control
- If on Ethambutol, baseline and monthly assessment
of visual acuity & colour discrimination
- Children: bloodwork not routinely required on children <16.
Consult with TB Control.
BLOOD WORK
- Monthly for side efects to drugs: rash,
malaise, loss of appetite, nausea and
vomiting, tingling of hands and feet
and vision changes.
MONITOR
- Recommended on all newly
diagnosed active cases
- Consent and Pre & Post
Counseling required
HIV SEROLOGY
- Q 2 months or as
recommended by
TB Control
X-RAY FOLLOW-UP SPUTUM
COLLECTION
- SMEAR POSITIVE: Hospital
or home until 3 negative
smears and on appropriate
treatment.
- CULTURE (+) SMEAR (-):
Isolation until 2 weeks
of treatment completed
ISOLATION
- See Contact
Tracing Algorithm.
CONTACT
TRACING
- See Contact Tracing Algorithm
CONTACT TRACING
40
SECTION III CONTACT INVESTIGATION
Goals of Contact Investigation | 41
Roles & Responsibilities | 41
Principles to Guide Contact Investigation | 42
Assigning Priority for Investigation of Contacts | 44
Conducting a Contact Investigation | 46
Contact Examination Procedure | 48
Contact Examination in Congregate Settings | 52
41
GOALS OF CONTACT INVESTIGATION
Identify any secondary cases of TB disease and initiate treatment as soon
as possible
Identify newly infected individuals and offer preventative treatment and/or
appropriate follow-up
Identify the source case (when the index case is not the source case)
Contact investigation is the responsibility of the Medical Health Of cer (MHO) in
the relevant Provincial Health Authority. TB Control provides consultation and
works collaboratively with the designate of the MHO. The designate may be local
public health nurses, community health nurses or a communicable disease unit
within a regional health authority.
TB Control maintains a central registry of all contacts in order to track and
assist with coordination of contact follow-up. TB Control is responsible for
communicating contact investigation information across health regions and
between provinces. It is important that all contact information is reported to
TB Control to ensure accurate and timely information is communicated to the
appropriate health care providers.
Public health nurses/community health nurses usually provide the front-line TB
screening of contacts and the following information is provided to assist these
nurses in the decision-making required when undertaking a contact investigation.
TB Control is available for consultation throughout the contact investigation
process.
The physician at TB Control will review the skin test and/or chest x-ray fndings of
all contacts and provide recommendations.
Contact investigation needs to be initiated as soon as possible after a diagnosis of
active TB. The diagnosis of active TB and the initiation of contact investigation are
usually the result of:
Notification that a respiratory specimen laboratory result is
smear positive for acid fast bacilli (AFB) and probe positive for
Mycobacterium tuberculosis (MTB).
Notification that a negative respiratory smear result is now culture
positive and/or probe positive for Mycobacterium tuberculosis.
In this setting the patient needs to submit a further 3
sputum specimens to determine if they have become
infectious (smear positive) during the time it took for
the culture to grow.
42
Active tuberculosis in young children is rarely infectious, but it is
usually a sign of a recent infection. Reverse contact investigation of
the childs close contacts should be done to identify the source case.
A clinical diagnosis of active TB in the absence of laboratory
confirmation should be discussed with TB Control to determine the
need for contact investigation.
Non-pulmonary TB cases may require contact tracing and should be
discussed with TB Control.
PRINCIPLES TO GUIDE CONTACT INVESTIGATION
1. INFECTIOUSNESS OF THE SOURCE CASE:
Cases of laryngeal TB and smear positive pulmonary TB are considered most
infectious.
Cavitary pulmonary TB is usually very infectious.
Adults and adolescents are generally more infectious than children under 10 years old.
Duration of symptoms, particularly a cough, increases the risk of infectiousness.
Poor respiratory hygiene (i.e. doesnt cover mouth when coughing and/or sneezing)
increases the risk of spreading TB.
Forceful exhalation such as shouting or singing increases the risk of spreading TB.
Cases of non-respiratory (non-pulmonary) TB are considered non-infectious once
pulmonary TB has been ruled out (ie. symptom inquiry, 3 sputum samples,
and chest x-ray) with the exception of irrigation of open TB site wounds due to
possible aerosolization of TB bacteria.
Contact investigation of non-respiratory TB is usually limited to household
contacts only, though investigation may expand depending on results of intial
CI. Children only require skin tests if asymptomatic. A chest x-ray is not required
in the absence of symptoms. Purpose of this screening is to locate the source
case.
2. PERIOD OF INFECTIOUSNESS
The period of infectiousness is usually considered to start at the time of onset
of cough. Individual clinical fndings may infuence the estimated period of
infectiousness. Consultation with TB Control is recommended if the client does not
report a cough.
The period of infectiousness ends when a client has received at least two weeks
of adequate treatment and has had 3 consecutive negative sputum smears. The
sputum specimens should be collected on 3 separate dayspreferably in the
morning.
43
3. AIR SHARING EXPERIENCE

Tuberculosis is an infectious disease transmitted almost exclusively by the
airborne route. The risk of transmission depends on the concentration of infectious
droplet nuclei in the air shared by the case and their contacts. It is unlikely
that transmission of TB can occur outdoors. Indoor environments that are
small, confned and poorly ventilated can lead to an increased concentration of
tubercle bacilli in the air. In a closed circuit heating or air conditioning system,
recirculation of air tends to increase the concentration of tubercle bacilli and
increase the possibility of infection.
Another factor in the air sharing experience is the length of time spent in the same
indoor environment (does not have to be home environment) with an active TB
case. Contacts should be divided into categories according to the number of hours
spent with the source case per week.
TABLE 3.1: TYPE OF CONTACT
TYPE OF CONTACT AMOUNT OF TIME WITH SOURCE CASE
Type 1 contact
More than four hours per week. Close household
contacts.
Type 2 contact
Two to four hours per week. Close non household
contacts who share the air space on an ongoing
basis (i.e. close friends)
Type 3 contact
Less than two hours per week. Casual contacts
such as sports teams.

Contacts exposed during high-risk medical procedures are at high risk of becoming
infected. These procedures include:
Bronchoscopy
Sputum Induction
Autopsy
Intubation
4. SUSCEPTIBILITY OF THE CONTACT
Any individual with no prior TB infection is at risk of infection when in contact
with an infectious case of TB. Prior treatment of TB infection or disease is believed
to reduce the risk of re-infection in individuals with healthy immune systems
although it does not completely remove the risk of re-infection
The most susceptible contacts are those contacts most likely to be infected with
44
the TB germ and those who are at a high risk of developing active disease once
infected. They include:
Children under 5 years of age
HIV positive
Immunocompromised
These high-risk contacts require a tuberculin skin test (TST) and a chest x-ray in a
contact investigation, regardless of TST result.
ASSIGNING PRIORITY FOR INVESTIGATION OF CONTACTS
The extent and order of contact investigation is based on the infectiousness of
the source case, extent of exposure to the source case, and the vulnerability of
the contact. Consultation with TB Control is advised to help establish a contact
investigation plan.
High-priority contacts usually include household contacts, contacts 5 years old and
under, those contacts who are immunosuppressed, and contacts with symptoms of
TB disease.
CONCENTRIC CIRCLE APPROACH TO CONTACT INVESTIGATION
The concentric circle (see Figure 1/page 45) approach to contact investigation is a
tool used to assist in determining who needs to be screened. Investigation begins
with close contacts of the source case. If close contacts have not been infected, it is
unlikely that casual contacts need to be screened.
If there is evidence of transmission of infection or secondary cases of active TB
in the close contacts of the case, then the next circle of type 2 contacts need to be
assessed and screened. Widening of the circle continues until there is no further
evidence of transmission of TB infection.
Contacts screening may include; individuals, groups or locations, sports teams,
religious gathering places, a persons hobbies, area of employment, after hours
activities, where a person sleeps (if outside of the home), activities of daily living
(pubs/bars/school or classes) etc.
Although guidelines for TB contact investigations (CI) have been based upon
concensus expert opinion, recent studies have documented limitations in the
outcomes of traditional CI, including issues with contact identifcation, screening
completion and LTBI treatment initiation and completion. The problems with
standard CI are amplifed in certain high-risk groups, such as homeless persons
and those struggling with issues of substance use who may be unable to recall
their contacts by name or other pertinent identifers.
45
T
Y
PE 1
T
YPE 2
T
YPE 3
Babysitter
Neighbours
Church
Groups
Parties
Hunting
Clubs
Dances
Local
Bar
Cofee
Shop
Bingo
Hall
Vacation Camping
Public Transport
Friends
Lunch
Room
Regular
Clients
Business Travel
Co-workers
Work
School
Regular
Meetings
Tenants
SOURCE
CASE
Regular
Overnight
Visitors
Household
Members
SOCIAL NETWORKING & LOCATION-BASED SCREENING
The concentric circle approach to contact investigation has not been very successful
in homeless and street involved populations. These populations are highly mobile,
often living unconventional lifestyles. Street involved people do not always know
the names of people they socialize with, or only know their "street names".

There is evidence that social networking is a more successful approach with this
population, especially in an outbreak setting. Social networking is an approach
where key individuals and locations that are central to the spread of disease are
screened. In addition to screening close named contacts, locations where the source
case frequents such as shelters or drop-in centres are screened. This approach better
characterizes relationships with contacts and helps to understand unrecognized
patterns of disease transmission. Screening high risk locations should be indicated
in the contact box on the HLTH 939 form.
A sample questionnaire is included in the appendix but it is important to realize
that the questionnaire may need to be modifed to refect the community being
investigated. Including a person in the process who is knowledgeable about the
community is often quite efective. TB Control can also provide the guidance in
implementation of network informed CI.
FIGURE 1: CONTACT SCREENING / SOCIAL NETWORKING
46
CONDUCTING A CONTACT INVESTIGATION
1. SOURCE CASE MEDICAL INFORMATION REVIEW

Laboratory results (smear status; dates)
Chest x-ray results
Symptoms
Onset of symptoms
2. INTERVIEW SOURCE CASE
The initial interview should occur as soon as possible after the case is diagnosed
with active TB. This interview should include a review of patients symptoms to
verify the period of infectiousness to identify the patients contacts and to fnd out
places where the patient spent time. It may take several interviews to obtain this
information.
The following information should be obtained;
Contact with children and their ages
Contact with anyone who is immunosuppressed
Household contacts
Close non-household contacts
Place of work, school, church and play
Other places where the patient may spend 2 or more hours/week
Social gatherings that may have occurred during the period of
infectiousness, such as weddings, funerals and community events.
Does the source case know anyone with signs and/or symptoms of TB?
Has the index case been traveling during the estimated period, or in
the last 2 years, of infection? If yes, obtain details of trip, including
means of transportation.
It is important to gather as much detailed information about the contacts as
possible to assist in the screening process. This information should include names,
dates of birth, addresses, and phone numbers. It may be useful to ask the patients
permission to interview family members or close friends to assist in gathering
contact information.
Assure the patient that their diagnosis of TB is confidential and will not be shared
with their contacts. Give the patient the choice of informing their own contacts.
Inform the patient that if their contacts have not reported for testing within a week
a public health nurse or community health nurse will follow-up with the named
contacts.
47
The interviewer needs to be sensitive to the concerns and beliefs that a patient may
be experiencing about having been diagnosed with active TB. The interview should
include education and information about active tuberculosis and its treatment.
The interview should be done in a respectful manner that helps to develop a
relationship of open communication. The interview may need to take place over
a period of time. Clients should be advised to contact PHN/CHN with additional
information (names, locations) that become apparent as time goes by.
A preliminary list of contacts should be established within 3 days (see Time Frame
for Contact Tracing page 54) of the diagnosis of an active case of tuberculosis and
sent to TB Control on a Follow-up Contact Assessment TB Control HLTH 836 (s) form.
If public health wishes, they can develop their own forms to meet their particular
needs but must capture the information listed on the HLTH 836 (s) form.
3. FIELD INVESTIGATION
A feld visit may be benefcial to assess the air sharing environment of the source
case. Environmental characteristics of the congregate setting should be assessed
and may assist in determining appropriate site screening. Size of the space, airfow,
number of windows are some of the important components in the assessment. The
visit may also provide additional information about potential contacts.

4. PRIORITY OF CONTACT SCREENING
All the information gathered in the above three steps should be used to determine
the probable risk of transmission. This assessment should then guide the priority
and initial extent of contact screening.
In almost all cases of active tuberculosis, the high priority contacts for screening
include household contacts, children under 5 years of age, immunosuppressed
individuals, and contacts with reported symptoms of TB.
Based on the initial risk assessment of transmission, a plan needs to be established
for priority contact screening. Every attempt should be made to follow the
established plan in order to use personnel resources where they are most needed
and to evaluate the outcomes of the contact circle that is being screened.
In small communities there can be the potential for "panic"and nurses may be
overwhelmed by the volume of casual contacts, and people who are not sure they
are contacts, wanting to be tested. In these situations, it is sometimes advisable
to schedule one or two screening clinics to diminish the anxiety of the casual
contacts, while allowing the nurses to concentrate, on the priority contacts.
48
CONTACT EXAMINATION PROCEDURES
INTERPRETATION OF TST RESULTS IN CONTACT SCREENING
TABLE 3.2: INTERPRETING TST RESULTS IN CONTACT SCREENING
SIZE OF INDURATION INTERPRETATION ACTION
0 to 4 mm Negative
Repeat TST in 8 Weeks
5 mm or more Positive
Send for chest x-ray

PRIORITY SCENARIOS:

1. CHILDREN UNDER 5 YEARS OF AGE
Children under 5 years of age have an increased risk of developing active TB
(primary disease) once they have been infected with TB. They are also at risk of
developing miliary TB or TB meningitis. Consequently, it is important to protect
these children with primary prophylaxis during the incubation period of TB
infection.
TB Control should be notifed immediately of all children under 5 years of age who
are close contacts of the source case. Initial testing of these children will include
a tuberculin test as well as a chest x-ray. A HLTH 939 form should be initiated.
If the TST is negative (0 to 4 mm) and the chest x-ray is normal, the child may
be recommended to start on primary prophylaxisIsoniazid syrup, or crushed
tablet, to be prescribed according to the childs weight. The child will have a repeat
tuberculin skin test in 8 weeks.
Children under six months of age may not be able to mount a TST response;
therefore primary prophylaxis (Isoniazid treatment) may be continued until a
repeat TST at six months of age. If this repeat skin test is negative, Isoniazid can be
stopped. If this repeat skin test is positive (5 mm or greater) the child will continue
preventative therapy for a total of 9 months.
Guidance from TB Control should be sought for all children under 5 years of age.
The TB Control physician will decide if a chest x-ray is required.
Infants will need to be weighed regularly to ensure that Isoniazid dosage is
adjusted to accommodate weight gains.
NOTE: Please see Appendix D for more information on Pediatric TB.
49
PEDIATRIC PRIMARY PROPHYLAXIS OF CHILDREN
PRIMARY PROPHYLAXIS
For Children < 5 years of age who are:
MEDICATION
- Close contact to active case of TB
- Contact TB Control; initiate HLTH 939
- Negative TST at baseline
- Normal chest x-ray
- Asymptomatic
- Prescribed & dispensed by TB Control
- Standard regime: Isoniazid x 2 months minimum
- Childs weight required to determine dose
BLOOD WORK
- Not required for children <16
MONITOR
- Side efects to drugs: malaise, loss of
appetite, nausea & vomiting
- Discontinue Isoniazid after
consulting with TB Control
AT 8 WEEKS
From initial TST
or
Last date of exposure
REPEAT TST
TST POSITIVE
TST NEGATIVE
& ASYMPTOMATIC
(5mm)
- Repeat CXR
- Consult with TB Control
NOTE: For children <6 months of age, refer to Pediatric Section (appendix D) and call TB Control
50
2. IMMUNO-SUPPRESSED CONTACTS
HIV positive and other immune suppressed contacts should have TST and a CXR
as soon as possible. If these contacts are symptomatic, 3 sputum specimens for
AFB should be submitted to the laboratory. These contacts may be ofered primary
prophylaxis if their initial TST is negative (04mm) and chest x-ray is normal.
A repeat TST should be done in 8 weeks. If the second TST is positive (5 mm or
greater) the individual will continue preventative therapy for a total of 9 months.
If the second TST is negative, it is possible the individual may need to continue
preventative therapy for a total of 9 months. The decision to stop or continue
preventative therapy is based on the individuals immune response and if it is
deemed capable of mounting a response to tuberculin. This will be assessed on an
individual basis in consultation with TB Control and often the clients specialist.
Notify TB Control of all HIV positive and other immune suppressed contacts. If
CD4 counts are available please fax to TB Control.
EXAMINATION OF ALL CONTACTS
A HLTH 939 form must be completed for each contact and sent to TB Control. It is
important to fll out all sections of the HLTH 939 to assist the TB physician to make
appropriate individual recommendations for each contact.
Assessment of each contact includes:
Demographics of the contact
Type of contact details can be written on HLTH 939 or faxed on a
separate sheet
TB number of source case (or PHN is TB # not available)
Medical risk factors (for developing TB disease)
Symptoms of TB (send 3 sputum specimens for AFB)
Past history of active TB or latent TB
Past history of treatment of active or latent TB
Previous documented TST results; BCG vaccination
TUBERCULIN SKIN TEST (TST)
A TST should be administered to contacts that have no documentation or history
of a previous positive skin test. The TST should be read at 48 to 72 hours.
If the TST result is negative, then a second TST should be administered 8 weeks
after the last exposure to the infectious case.
If the second TST remains negative and the individual has no signs and/or
symptoms of TB, no further follow-up is required.
If the first or second TST is positive with a history of a negative TST, then
the contact is a converter and assumed to have been recently infected with
TB. Further investigation including a chest x-ray and sputum investigation
(if symptomatic) is needed to rule out active TB disease.
51
Without intervention, approximately 5% of newly infected individuals will
develop active tuberculosis within 2 years. These individuals are candidates for
preventative treatment.
If no documentation of a previous negative TST, client may still be a converter and
a candidate for preventative prescription.
NOTE: a second TST for contacts is not required if the initial testing was done eight weeks after
contact and no further contact was maintained.
Send completed HLTH 939 to TB Control. If known, please indicate on HLTH 939
form where the client is going for chest x-ray.
CHEST X-RAY
Arrange for chest x-rays for contacts who are previously known to be skin test
positive, giving priority to those who are symptomatic
Arrange for chest x-rays for contacts who have a newly positive TST
Children under 5 years of age require a chest x-ray regardless of TST status
HIV positive and severely immune suppressed individuals require a chest x-ray
Send completed HLTH 939 and a copy of normal chest x-ray report to TB Control.
Abnormal chest x-ray reports should be accompanied by the x-ray flm/CD of
available, otherwise the chest x-ray will be accessed via "the grid".
The TB physician will make recommendations for all contacts with positive TSTs.
If indicated on the HLTH 939, a narrative will be sent to the GP, the local public
health unit or the community health centre.
SPUTUM EXAMINATION
Obtain three sputum specimens for laboratory examination on all contacts with
a cough of over 3 weeks in duration and/or other TB related symptoms. If possible,
collect three sputums on all HIV positive contacts regardless of symptoms.
PREVENTATIVE THERAPY FOR CONTACTS
Preventative therapy should be considered for all close contacts of infectious cases
that have positive tuberculin skin tests. (See Section IV on Prevention)
When preventative therapy is not accepted or completed, a chest x-ray and
symptom review should be done every six months for two years. If the client
becomes symptomatic, three sputums should be collected for AFB and culture and
a chest x-ray should be repeated.
52
CONTACT INVESTIGATION IN CONGREGATE SETTINGS
In some circumstances it may be necessary to investigate a number of contacts in
a congregate setting such as a school, workplace, homeless shelter, etc. In these
settings it is usually advisable to try to arrange contact screening at the actual site.
The following should be considered:
Visit the site prior to the contact screening date to view the area and
organize the screening session.
Provide information sessions/education prior to screening session.
If possible, have the demographic area of the HLTH 939 form filled
out before the contact screening session.
Provide adequate staffing for the screening.
Communicate with local radiology facility to make arrangements for
possible increased flow of clients.
If large numbers of contacts are being referred to the Vancouver or New
Westminster TB Clinics please phone ahead so the clinics can adjust their
schedules to accommodate the increased volume of clients.
HOSPITALS
Any patient in hospital with symptoms or other evidence suspicious for TB should
be isolated as soon as possible. The patient should be in a negative pressure room
(if available) or a private room on respiratory precautions.
The hospital staf should contact TB Control and the local health authorities when
an active case of TB is diagnosed while in hospital.
It is the responsibility of the hospitals occupational health program to test
staf who may have been exposed. In hospitals without an occupational health
program, arrangements need to be made with the local public health unit.
Infection control should make the arrangements for inpatient contacts to be
tested. A list of contacts should be forwarded to the local public health unit and TB
Control by infection control and/or occupational health to ensure continuity of CI,
especially in those contacts subsequently discharged from hospital.
Public health is responsible for contact tracing of patients outside the hospital
setting (i.e. family, friends and co-workers). An interview should be done with the
source case to gather contact information about their contacts.
A HLTH 836 Form should be used to gather data and forwarded to TB Control
when complete.
If a hospital decides to send exposed staf with positive skin tests to TB Control
Clinics (Vancouver or New Westminster) for evaluation, a chest x-ray should be
done at the hospital of employment prior to attending an appointment at a TB
53
clinic. The staf member should bring the TB screening form (HLTH 939) and a
copy of the chest x-ray report if normal and/or flm/CD if x-ray is abnormal for
their appointment with the TB clinic doctor.
AIRPLANE TRAVEL
The Public Health Agency of Canada (PHAC) assists in contacting airlines for
passenger lists of people that were sitting near an individual with infectious
pulmonary tuberculosis. Contact investigation needs to include asking the source
case the dates of travel, where they travelled, and the mode of transportation.
TB Control will fax the local public health unit the airline contact information so
CHN/PHNs can do follow up with any clients who were a contact on the fight.
Once the client is found, a TST and symptom review is done, as well as a chest
x-ray if TST is positive. The form can then be completed and faxed back to TB
Control so PHAC can be notifed of the appropriate follow up.
54
TIME FRAME FOR CONTACT TRACING
INTERVIEW THE FOLLOWING:
- CXP
- |f symptomatlc, collect 3 sputum
INDIVIDUALS WHO HAVE A RECORD
OF A PREVIOUS POSITIVE SKIN TEST:
- TST < 5mm: Pepeat ln 8 weeks
- Symptomatlc: CXP & 3 sputum
(regardless of TST results)
- TST > 5 mm: CXP
*
- Chlldren < 5 years: TST & CXP
**
- |mmunosuppressed: TST & CXP
***
(|f TST > 5mm)
INDIVIDUALS WHO ARE PREVIOUS
NEGATIVE OR OF UNKNOWN STATUS
PROVIDE TST:
ESTABLISH CONTACT LIST
WITHIN 3 DAYS
CONTACT TRACING SHOULD
BEGIN WITHIN 7 DAYS
OF SOURCE CASE REPORT
Only interview family/close friends if condentiality
consent has been received from source case.
- Source Case
- Pamlly
- Close Prlends
- |nltlal round of TSTs and CXPs should be
completed wlthln 30 DAS of the lndex case
belng reported
- Call T8 Control lf asslstance ls requlred wlth
Contact Traclng
* treatment of LTBI prophylaxis should be considered once active
disesase is excluded.
** Children under 5 years of age who are close contacts should be
considered for Isoniazid primary prophylaxis regardless of initial
TST result. Treatment may be stopped if repeat TST at 8 weeks post-
exposure is negative.
*** HIV individuals who have a negative TST and are close contacts
should be considered for preventative therapy.
55
SECTION IV PREVENTION
Preventative Therapy | 56
Rifampin Preventative Treatment | 60
Medication Reordering Instructions | 62
for Latent TB Infection
56
PREVENTATIVE THERAPY
Treatment of latent tuberculosis infection (LTBI) is a therapeutic regime using
medication to treat an individual infected with the TB bacilli before they develop
active disease.
RATIONAL

A signifcant number of tuberculosis cases result from individuals previously
infected with M. tuberculosis. There is a 5 to 10 per cent risk of developing active
disease over the lifetime of an infected individual with a healthy immune system.
For those who are immuno-compromised, the risks can be signifcantly higher.
Preventative therapy is important in order to achieve the goal of reducing TB rates.
Although there are other treatment options available, the most common
preventative treatment is monotherapy with the drug Isoniazid and Vitamin B6 for
a period of 9 months. The use of one drug is based on the fact that there is a small
concentration of TB bacilli in latent infection and consequently the probability of a
resistant strain is very small. These recommendations are supported by evidenced
based research.
RECOMMENDATIONS FOR THERAPY
TB Control is responsible for prescribing preventative TB therapy and therefore
referrals for evaluation for preventative therapy should be made to TB Control.
The referral consists of a detailed history indicated on a Health 939 form and
a recent chest x-ray (within six months). The physician at TB Control will
review information provided and make a recommendation regarding further
investigation and/or preventative therapy. This recommendation will be forwarded
to the family physician and the public health unit/community health centre.
In situations where local physicians wish to implement preventative therapy, the
prescription and relevant information (CXR and TST results) should be forwarded
to TB Control where the TB physician will review the information and write the
prescription for treatment.
The decision to recommend preventative therapy is based on several factors:
Context of the TST needs to be investigatedis the positive
TST truly positive or does it reflect a response to an atypical
mycobacterium or BCG?
Is the client a contact of an active case or have they travelled
extensively in a country with high incidence of TB?
The likelihood of progression to active disease needs to be
determined. See chart on next page.

57
RISK TO PROGRESSION OF DISEASE
Low Risk
Positive Tuberculin Skin Test (TST), no known risk factor,
normal chest x-ray
Moderate Risk
Diabetes
Underweight ( less than 90% ideal body wt. BMI less
than 20)
Under 5 years old when infected
Abnormal Chest X-ray compatible with previous
granulomatous disease
Smoking
Alcohol and drug use
Tumor necrosis factor (TNF) alpha inhibitors
High Risk
Acquired Immunodeficiency syndrome (AIDS)
Human Immunodeficiency infection (HIV)
Transplantation (related to immunosuppressant therapy)
Silicosis
Chronic renal failure/hemodialysis
Carcinoma of head and neck
Recent TB infection (within 2 years)
Fibronodular disease on chest x-ray with positive TST
Possible intolerance to the medicationmedical conditions such as
severe liver disease and/or medications that are contraindicated
(i.e. Carbamazepine) with Isoniazid.
Ability to complete therapy do they have a stable living situation or
are they transient? Homelessness or street involved persons should
not be excluded from treatment. It is often amongst this population
that there are higher rates of TB disease. Every effort should be
made to provide them with preventative therapy and support.
Alcohol use history; risks for viral hepatitis, acetaminophen intake.
Desire for pregnancy.
58
TREATMENT INITIATION
The client will be informed of all aspects of treatment after the recommendation
for preventative treatment has been received by the health unit and/or physician.
Side efects, length of treatment, rationale for treatment, and importance of
adherence should be discussed and understood by client.
The client consents to treatment by signing the Preventative Therapy Request Form:
(http://www.bccdc.ca/NR/rdonlyres/9F06251A-951B-4DAF-BDA2-0D0989F66862/0/
RequestforPreventativeTherapyForm.pdf ) The form should be signed by both the
client and a PHN/CHN or physician. The form outlines responsibilities for both
the client and health care provider for the duration of the treatment. This includes
taking the medication, monitoring blood work and reporting adverse events and
side efects. Method of medication administration should be indicated on the form.
This will be either self-administered, in which the client will be provided with one
month supply of medication, or Directly Observed Preventative Therapy (DOPT)
which medication will be supervised twice weekly. When DOPT is the method of
delivery, no carries should be provided and all doses must be witnessed.
The Request for Preventative Therapy Form should be faxed to TB Control,
whereupon a prescription will be written and the medications will be sent. Two
months of medication will be shipped from the provincial pharmacy. Do not use
the medications from the starter kits to initiate preventative therapy. With self-
administered treatment, the Medication Re-order Form should be sent after the
frst month of medications are provided to the client. This will ensure continuity
of treatment and an ongoing record of adherence. When DOPT, is employed the
Medication Administration Record (see Appendix Q) should be flled out and will
serve as the re-order form.
PREVENTATIVE THERAPY REGIMENS
The frst line medication in preventative therapy is Isoniazid. There are extensive
research studies that support its efectiveness. A nine month regime provides over
90 per cent efectiveness and a six month regime provides 65 per cent to 70 per
cent efectiveness.
ADULT PROTOCOL
Izoniazid 300 mg daily (270 doses) or 900mg twice weekly (78 doses)
Vitamin B6 25 mg daily or Vitamin B6 50mg twice weekly
An alternate preventative therapy regime is Rifampin. It is used when Isoniazid
is not tolerated or there is Isoniazid resistance. There is ongoing research as to its
efectiveness but is not supported to the same extent as Isoniazid. The standard
adult dosage for Rifampin is 600mg daily for 4 months

59

There are often periods of non-compliance and TB Control recommends the
following timelines for completion of therapy:
A 9 month regimen must be completed within 12 months

Doses for children and small adults are calculated based on weight and Vitamin
B6 is not required for children under the age of sixteen.
MONITORING
Routine monitoring consists of the following:
Assessing for side effects. Any symptoms of hepatitis (nausea,
abdominal pain, vomiting, jaundice, dark urine) should lead
to immediate discontinuation of treatment and review by TB
physician, Isoniazid side effects and nursing implications.
SIDE EFFECT NURSING ACTION
Symptoms of hepatitis:
nausea, vomiting,
decreased appetite,
jaundice, fatigue or dark
yellow urine.
Hold medications, assess patient for side effects, get an
AST level.
Contact TB Control and if immediate concerns, contact
the local physician for further advice.
Clarify other issues related to liver i.e. viral hepatitis risk,
alcohol consumption, acetaminophen or NSAID use.
Upset Stomach
Clarify time of upset stomach
If near time of medication offer crackers or other
low fat food
If lasting all day long stop medication and send
for AST level
Contact TB Control
Isoniazid syrup may cause diarrhea in children. If this
occurs, switching to crushed tablets may help
Itching
Clarify if patient is able to tolerate. If not, contact TB
control sometimes an antihistamine may help itch
60
Rash
Clarify extent
Hold medication and contact TB Control
May need to be evaluated by local physician, as many
reasons for rash
More common in children.
Numbness & Tingling of
Extremeties
Clarifty extent
May need to increase Vitamin B6 to 50mg contact TBC
Fatigue
Encourage patient to take medication in evening. If
fatigue persists, may be related to elevated liver enzymes-
check AST level
Mood Changes: Irritability
or Depression
Evaluate cause of mood change discuss with TB control
Evaluate risk for suicide and act accordingly
RIFAMPIN PREVENTATIVE TREATMENT
Although Rifampin prophylaxis is usually only ofered when Isoniazid is unable to
be used, there is growing evidence of its success as a preventative agent.
The main advantage of Rifampin appears to be that the clients experience fewer
side efects than with Isoniazid. Rifampin also has a shorter treatment length
which makes it more attractive to patients with a higher likelihood of compliance.
The disadvantage of Rifampin is that only a few studies have been conducted using
the drug as monotherapy therefore its efectiveness is not as well documented, but
there are studies to support its equivalent ef cacy to Isoniazid.
Rifampin has its own side efects and also interacts with signifcantly more drugs
than Isoniazid.
61
RIFAMPIN SIDE EFFECTS AND NURSING IMPLICATIONS
SIDE EFFECTS NURSING IMPLICATIONS
Urine, sweat, stool and
tears may turn orange
May stain and damage soft contact lenses. If they have
soft contacts wear glasses instead.
Nurse needs to educate to alleviate potential anxiety
Interferes with all birth
control pills
Potential unplanned pregnancy
Use alternative contraceptive method
Interactions with multiple
drugs
(See medication interaction
section Appendix C)
Be aware of all medication patient is taking and advise
TB Control and family doctor
Monitor patient for drug interactions
Symptoms of hepatitis:
nausea, vomiting, fatigue,
jaundice, decreased
appetite or dark yellow
urine
Potential drug induced hepatitis.
Hold medication: consult TB control and/or patients
physician
AST level
Flu Like Symptoms fever,
chills
Stop medication: consult TB Control

ROUTINE BLOOD WORK MONITORING:
Baseline AST levels are recommended prior to starting treatment and if normal
every month for 3 months, then they can be done every 2 months after. If client
has underlying liver disease then AST should be repeated after 2 weeks with
further testing in consultation with TB Control and/or local physician.
Children under 16 do not require blood monitoring unless there are complicating
health issues. Discuss with TB Control.
RISK OF DRUG-INDUCED HEPATITIS
Mild elevation (3 to 5 times the normal value) of AST/ALT occurs in 10 to 20 per
cent of persons taking Isoniazid. In most instances, enzyme levels return to normal
without discontinuing the medication.
The risk of developing active TB disease must be balanced with the risk of
developing Isoniazid or Rifampin toxicity.
It should be noted that other drugs such as alcohol, acetaminophen and others
may contribute to drug-induced hepatitis and patients should be made aware.
62
GUIDELINES FOR MONITORING AST LEVELS
The following guidelines are recommended by TB Control when monitoring AST
levels of clients taking Isoniazid or Rifampin therapy. It is important to always
assess the client for signs and symptoms of hepatotoxicity in combination with AST
levels. The health care provider should also assess for any change in medications,
alcohol consumption, and or acetaminophen that may contribute to an abnormal
AST. When an elevated AST (greater than 45) report is received the patient should
be contacted ASAP and within 24 hours for a symptom assessment. If the report is
received on a Friday, the client should be contacted that day. The "Prophylaxis:
Notifcation of Abnormal AST Form" should then be completed and faxed to
TB Control.
GUIDELINES FOR MONITORING AST LEVELS IN PATIENTS TAKING
MEDICATION FOR LATENT TB INFECTION
AST LEVEL SYMPTOMS ACTION
AST greater than 45 and
less than 100
NO
Continue Treatment. Repeat
bloodwork in 2 weeks.
AST greater than 45 and
less than 100
YES
Repeat bloodwork in 1
week.
100 or higher NO/YES
Stop Treatment: Notify TB
Control. Repeat bloodwork
weekly until reaches
baseline AST.
NOTE: If a client has an elevated AST on preventative therapy and medication has been completed,
the AST levels should be repeated weekly until AST reaches baseline.
MEDICATION REORDERING INSTRUCTIONS FOR LATENT TB INFECTION*
STEP 1:
After a Request for Initiation of Treatment Form with the necessary information is
received, a prescription will be written and two months of medication will be shipped.
STEP 2:
Dispense 1 month of medication at a time.
Reorder using the Tuberculosis Medication Reorder Form (HLTH 850) after
first months medication is administered so that there is a 1 month supply always
63
available. This will ensure no shortage of medication in the event of an ordering/
supply problem. The subsequent supply will be for 2 months.
Ensure that the 'yes' box is checked requesting more medication. The AST results
are no longer required in the 'Test Done' and 'Results' section of the form. Normal
AST results need not be sent to TB Control as there is a separate form for the
abnormal ASTs; "Prophylaxis: Notifcation of Abnormal AST Form"

STEP 3:
Each subsequent reorder form will initiate a 2 month supply. Please ensure that the
compliance section is complete and the medication reorder 'yes' box is checked.
STEP 4:
The last reorder form will be sent in at the end of treatment and should contain
the compliance record and the reorder boxes will indicate no more medication
required.

NOTE: Because the time between reordering medications has been extended there will be a delay
in TB Control receiving compliance records. If the patient shows poor compliance please notify TB
Control via fax or phone as soon as possible.
Instructions apply to isoniazid treatment only. When rifampin is used 2 months
will be shipped out requiring only one reorder for a total of four months.
If you have any questions please contact TB Control.
COMPLETION OF PREVENTATIVE THERAPY
After completion of nine months of isoniazid or four months of rifampin, the nurse
should send a Completion of Treatment Form to TB Control. Most people require no
further follow-up, however, if the client had an abnormal chest x-ray at the start
of therapy and an exit chest x-ray was requested by the TB Control physician, it is
recommended to complete this request in the last month of LTBI treatment.
64
POSITIVE TST
-
Normal CXR
-
Productive Cough
and/or abnormal CXR
-
Submit 3 sputum -
TB Physician may ofer treatment
for LTBI
-
PHN/CHN provides education
(pamphlets provided on Web)
-
Client in consultation with health
care provider agrees to LTBI
prophylaxis
-
Client signs Request for
Preventative Therapy form
Smear (+) or
Culture (+)
Sputum
See Algorithm:
Management of
Actlve Cases
Smear (-) &
Culture (-)
x 3 Sputum
-
No Signs & Symptoms
of Tuberculosis
-
Prescribed & dispensed* by TB Control
-
Isoniazid & Vitamin B6** x 9 months

-
DOT twice weekly or daily self-administered
-
Rifampin x 4 months
-
Daily DOT or self-administered

MEDICATION
-
Baseline: AST (not required <16 yrs old)
-
Q monthly for frst 3 months; AST
-
Then, if ASTs are normal, Q 2 months for duration
of treatment
BLOODWORK
-
Monthly for side efects: malaise, N&V, jaundice,
tingling in extremities, rash, loss of appetite,
and/or fatigue
-
Contact TB Control for abnormal lab values
(see Guidelines for Monitoring AST page 62)
MONITOR
TREATMENT OF LATENT TUBERCULOSIS INFECTION (LTBI)
*Please do not use starter kit, wait for pharmacy to send LTBI medication
**Children under 16 years of age do not require Vitamin B6
http://www.bccdc.ca/NR/rdonlyres/C069835C-3141-4D24-9266-ED6D5957E85B/0/NotificationofAbnormalASTform.pdf
65
SECTION V APPENDIX
Appendix A Glossary 66
Appendix B Basic Facts about Tuberculosis 71
Appendix C Medications 74
Appendix D Pediatric TB 92
Appendix E TB Services for Aboriginal
Communities 96
Appendix F BCG Vaccine 118
Appendix G Tumour Necrosis Factor 120
Appendix H Atypical Mycobacteria 122
Appendix I TB & HIV 125
Appendix J Multiple Drug Resistent TB 127
Appendix K Directly Observed Therapy 129
Appendix L Interim Guidelines for use 132
of IGRA Studies
Appendix M Molecular (Diagnostic Tools) 133
Appendix N Immigration 135
Appendix O Tuberculosis & Chronic
Renal Failure 138
Appendix P Sputum Induction 140
Appendix Q Forms 142
66
APPENDIX A: GLOSSARY
Acid-Fast Bacilli (AFB) Bacteria that retain certain stains after being washed
with acid alcohol. Many mycobacterium, including Mycobacterium tuberculosis, have
this property.
Acquired Drug Resistance Resistance to one or more drugs that develops after
the person is on drug therapy.
Active Infectious Tuberculosis A person with pulmonary tuberculosis with a
positive sputum on smear. A person with positive sputum on culture only may be
potentially infectious.
Aerosol Small droplets of moisture that are exhaled or coughed up; may contain
Mycobacterium tuberculosis bacteria and if suspended in the air can lead to the
spread of infection.
Adherence Also called compliance. Refers to person complying with all aspects of
their treatment regimen.
Anergy The inability of a person to react to skin test antigens because of defects
in delayed hypersensitivity. The person may still have tuberculosis infection, but
unable to mount an immune response to the test antigen. Tests are available for
anergy.
Bactericidal Agent that can kill bacteria.
Bacteriostatic Agent that prevents bacterial growth but does not kill bacteria.

BCG Vaccine Bacille Calmette-Gurin vaccine is an attenuated strain of
Mycobacterium bovis and is used to protect against tuberculosis.
Booster Phenomenon the booster efect or recall phenomenon is based on
the waning of delayed-type hypersensitivity (DTH) over time and its recall by a
subsequent tuberculin skin test.
Caseous A type of tissue necrosis that has a cheese like consistency.

Cavitary Disease This is a radiologic-pathologic label referring to evidence of
lung destruction. Cavities generally harbour large numbers of bacteria and as a
result patients with cavitary disease tend to be highly infectious.
Cell-Mediated Immunity A type of immune reactivity in which T-lymphocytes
participate.

67
Contact A person who has shared the same air with a person with infectious TB.
It usually means that there is a possibility of transmission of TB occurring.
Culture Growing micro-organisms in the laboratory for their identifcation.
Delayed Hypersensitivity A type of cell-mediated immune response that occurs
when T cells encounter their specifc antigen and lymphokines are released.
Directly Observed Therapy (DOT) Treatment in which each medication dose is
taken under the supervision of a health care worker or trained person. DOT with
preventative therapy is also referred to as DOPT
Droplet Nuclei Microscopic particles produced when a person coughs, sneezes,
sings, or shouts. These droplets (1 to 5 microns in diameter) can carry M. tuberculosis,
and can remain suspended in the room air for short periods of time (e.g. at 1 air
exchange per hour a volume of fresh air equal to the room volume each hour
will take 276 minutes to reduce the concentration of AFB in the air at 99%).
Drug-Resistant TB TB that is not susceptible (i.e., is resistant) to one or more
anti-TB medications.
Endogenous Reactivation Reactivation of dormant foci of M. tuberculosis inside
the body from a previous infection.
Erythema Nodosum An acute infammatory skin disease marked by tender red
nodules. The lesions appear in successive patches during a period of several weeks.
The rash, though not specifc for TB, is associated with primary infection.
Exogenous Reinfection Tuberculosis caused by an external source of
M. tuberculosis in someone who had a previous tuberculosis infection.
Extensively-Drug Resistant tuberculosis (XDR-TB) Tuberculosis due to bacteria
resistant to at least Isoniazid and Rifampin from among the frst-line anti-TB
drugs plus resistance to any Fluroquinolone and to at least one of three injectable
second-line drugs.
Extrapulmonary TB TB in the body outside of the lungs and may include lymph
nodes, spine, kidneys, joints, eyes, and other organs throughout the body.
Ghon Complex A parenchymal lung lesion resulting from healing of the primary
infammation due to tuberculous infection. Often accompanied by hilar gland
calcifcation and referred to as "Healed Primary Complex".
HEPA Filter A high ef ciency particulate air flter that removes almost all air
particles greater than 0.3 microns in diameter and is used as an environment
control to lessen the spread of TB.
68
Interferon Gamma Release Assay (IGRA) In-vitro T-cell based assays that
measure interferon gamma production which have been developed for the
diagnosis of latent TB infection. These assays operate on the basis that T-Cells
previously sensitized to tuberculosis antigens produce high levels of interferon
gamma when re-exposed to the same mycobacterial antigens. There are two
diferent types of IGRAs: QuantiFERON Gold and T-Spot.
Index Case The frst or initial active case from which the process of contact
investigation begins.
Induration The area of frmness or swelling that surrounds the site of tuberculin
injection (Mantoux test or TST) and is read and recorded in millimeters.
In Vitro In the laboratory or test tube.
Intermittent Therapy Therapy administered 23 times a week. Should only be
given by DOT or DOPT and is not to be self-administered.
Latent Tuberculosis Infection The presence of latent or dormant infection with
Mycobacterium tuberculosis with no evidence of clinically active disease. Subjects
deemed to have LTBI are by defnition non infectious.
Mantoux Test A type of tuberculin skin test in which purifed protein derivative
(PPD) is introduced intra-dermally.
Miliary Tuberculosis A type of TB that is hematogenous, generalized or
disseminated; so-called because the disease causes lesions that resemble millet
seeds when viewed on the chest radiograph.
Multiple Drug Resistant TB (MDR-TB) Case of tuberculosis caused by a strain of
Mycobacterium tuberculosis resistant to both Isoniazid and Rifampin.
Mycobacterium Tuberculosis The microorganism causing tuberculosis.
NTM Nontuberculous mycobacteria includes all mycobacterial species except
those that cause tuberculosis (TB).
Positive Culture Sputum or other specimens that grow colonies of Mycobacterium
tuberculosis on a culture. This provides confrmation of tuberculosis.
Positive PPD Reaction Reaction (equal to or greater than 10mm) to tuberculin
skin testing with PPD that suggests the person has been infected with tubercle
bacilli.
Positive Smear Sputum or other specimens found to be positive (large number of
bacilli) for acid-fast bacilli on direct microscopic examination.
69

Primary Drug Resistance Infection with an organism from a source case with
resistant disease.
Primary Tuberculosis Refers to TB that occurs in a person not previously infected
with M. tuberculosis. Usually thought to have occurred from TB infection within the
preceding 24 months.

PCR Polymerase Chain Reaction is a technique for amplifying DNA sequences in
vitro. A specifc DNA sequence can quickly and accurately be magnifed by billions.

Reactivation The development of active TB disease after a period of latent TB
infection.
Smear Reported by the lab using a grading system with the numbers 14. The
quantity of stained organisms is associated with the degree of infectiousness.
Source Case A person who has or has had active infectious tuberculosis and is the
primary source for the transmission of the tubercle bacillus. This person may be the
index case for his/her contacts or one or more of the contacts of the index case.
Tine Test A type of multiple puncture tuberculin skin test. Popular in Europe.
Tubercle Bacilli A collective term to refer to organisms in the Mycobacterium
tuberculosis complex or to M. tuberculosis.
Tuberculin Convertor Any person with a tuberculin reaction which has onverted
from a "negative" or "doubtful" reaction to a "positive" reaction (10mm or greater).
Tuberculin Reactor Any person who reacts to the standard dose of tuberculin
5TU with a diameter of induration of 10mm or greater.
Tuberculosis (TB) A chronic bacterial infection due to Mycobacterium tuberculosis,
characterized pathologically by the formation of granulomas. The most common
site is the lung (pulmonary TB), but other organs may be involved (extrapulmonary
TB).

Two Step Testing The purpose of two step testing is an attempt to reduce the
efect of the booster phenomenon. The initial test should be planted and the
second test done 14 weeks later.
Virulence The ability of a micro-organism to produce disease.
70
APPENDIX B: BASIC FACTS ABOUT TUBERCULOSIS
Tuberculosis is an infectious disease caused by the Mycobacterium tuberculosis
bacteria. Mycobacterium bovis, a genetically related mycobacterium, found in
unpasteurized milk can also cause tuberculosis but has largely been eradicated in
Canada through pasteurization and the culling of those animals found to host the
bacteria.
CHARACTERISTICS OF TUBERCLE BACILLUS
Highly aerobic (but can survive in an anaerobic environment) and consequently
found in oxygen rich areas of the human bodye.g. apices of the lung, renal
cortex.
Humans are the main reservoir of the organism.
It reproduces slowly and may lie dormant for many years
Its high lipid content enables an acid-fast staining characteristic whereby it can be
microscopically determined on direct smear.
It requires 3 to 8 weeks to demonstrate colonies in a culture media
TRANSMISSION OF TUBERCULOSIS
Transmission occurs primarily through airborne droplets of moisture that evaporate
and create "drop nuclei".
Transmission occurs when a person with pulmonary TB coughs, sneezes, laughs or
talks and expels droplets of moisture containing tubercle bacilli. They become
droplet nuclei and remain suspended in the air for a number of hours.
There are a number of factors that contribute to transmission: the number of bacilli,
the environment (poor ventilation enhancing transmission), the duration of
exposure, the strain of the bacilli, and the susceptibility of those exposed.
The main source of infection is cases with a productive cough containing enough
organisms to be viewed with a microscope (smear positive).
Those cases that are smear negative but culture positive are deemed to be at low risk
for infecting others. Extra pulmonary TB is not a source of transmission.
Individuals diagnosed with TB have been infected by another person often a close
contact at some point in time. If the case is a child, transmission will have been
recent. The index case, or the frst case, to be diagnosed is not necessarily the
source case (the case thought to have spread the infection.)
When TB infection occurs and does not evolve into primary disease (disease
occurring in the frst two years post infection) it is designated latent infection.
Latent infection can reactivate at any time but most often when the immune
system becomes compromised (HIV, cancer, and diabetes).
TRANSMISSION MAY BE MINIMIZED BY:
Prompt treatment of cases with anti-tuberculosis medication reducing the number of
bacilli and the symptoms (cough)
Covering the mouth with a tissue or mask. Clients who are smear positive should
wear masks (Surgical masks are deemed adequate). It is recommended that persons
providing care should wear N95 masks
71
Isolation, employing a negative pressure room or reducing the amount of re-
circulated air can reduce transmission but does not replace efective treatment.
Where practical, ultra violet light may be installed.
DISEASE PROCESS
In the event that TB infection occurs it can lead to primary disease or latent
infection. There is a 5 to 10 per cent chance of reactivation of latent infection
progressing to active disease in an immuno-competent person. Depending on
the risk factors, such as HIV and diabetes for example, there can be a signifcant
increase in the possibility of reactivation to active disease.
TB INFECTION
In immuno-competent persons the inhaled "droplet nuclei" implant at the
level of the alveolar sacs. The alveolar macrophages ingest the TB bacilli and
attempt to destroy them. Failure to limit replication triggers the Cell-mediated
immunity (CMI) and the delayed-type hyper-sensitivity (DTH) systems. The site of
implantation may be insignifcant and the infection is usually contained. There
may be lymphatic spread and occult bacteremia whereby it may spread to sites
that are oxygen rich such as the apices of the lung, renal cortex, and the ends
of the long bones for example, but at this point there is only infection and not
disease. There is some evidence to suggest that it can take from 18 to 24 months
for the immune system to mature. It explains why there is an increase risk for
developing active TB in those two years following the initial infection.
PRIMARY TB DISEASE
If the immune system fails to successfully contain the infection it can progress to
primary TB Disease. It presents often as a sub clinical or mild self-limiting illness.
Symptoms can include fever and non-productive cough and imaging may be
abnormal. Pleurisy with efusion usually follows infection by some months; it is
particularly liable to occur in older children, adolescents, and young adults. Very
often the preceding primary infection is undetected and pleurisy with efusion is
the frst manifestations of Tuberculosis. Primary TB in children often involves the
intrathoracic lymph nodes and less often the lung parenchyma.

TB MENINGITIS
TB meningitis is a very serious form of tuberculosis requiring quick intervention
to prevent serious neurological damage or mortality. It usually occurs weeks to
months after infection and is manifested by a progressive febrile illness associated
with headache, vomiting, and later, signs of meningitis such as stif neck. At risk
are children (under 2 years old) and those with HIV. BCG can reduce the incidence
of TB meningitis in children.
MILIARY TUBERCULOSIS
Miliary TB is caused by widespread dissemination of the bacteria via the
loodstream. It derives its name from the radiological appearance of a millet grain
pattern. It usually presents as a severe febrile illness and often accompanies
72
meningitis. The presentation can often be non-specifc and variable making a
diagnosis dif cult.

PERIPHERAL TB LYMPHADENITIS
Peripheral TB lymphadenitis involves the extra-thoracic lymph nodes and the
cervical nodes are the most common ones to be infected. The person usually
presents with a unilateral non-tender neck mass which may drain spontaneously
after a period of time. It is important to diferentiate between atypical
mycobacteria and TB mycobacteria in children under fve years old. Diagnosis is
often made on the basis of an excision or fne needle aspirate.
BONE AND JOINT
TB of the bone and joint typically arises in the growth plates of the bones where
the blood supply is the richest. Fifty per cent of joint TB involves the spine (Potts
disease) as the vertebral bodies are very vascular supporting bacteria replication.
The infection can spread to adjacent joint spaces resulting TB arthritis. There are
usually no constitutional symptoms instead local manifestations such as pain and
fuid collections.
GENITOURINARY TB
At the time of primary infection TB may seed the vascular renal cortex and onset
of disease is located here. It then can spread to the other areas of the kidney,
ureter, and bladder. It is most often unilateral so that kidney failure is not a
sequalae. Onset of the disease is insidious and patients are often asymptomatic.
Routine urine samples may show many white blood cells, but no bacteria (aseptic
pyuria).
7
3
A
P
P
E
N
D
I
X

C
:

M
E
D
I
C
A
T
I
O
N
S
T
a
b
l
e
1
F
i
r
s
t
-
L
i
n
e

D
r
u
g
s

f
o
r

T
u
b
e
r
c
u
l
o
s
i
s

T
r
e
a
t
m
e
n
t

1
D
r
u
g
P
r
e
p
a
r
a
t
i
o
n
s
A
d
u
l
t
s
C
h
i
l
d
r
e
n
A
d
v
e
r
s
e

E
f
f
e
c
t
s
U
s
e

i
n

P
r
e
g
n
a
n
c
y
C
N
S

P
e
n
e
t
r
a
t
i
o
n
M
o
n
i
t
o
r
i
n
g
I
s
o
n
i
a
z
i
d
T
a
b
l
e
t
s

(
5
0

m
g
,

1
0
0
,

m
g
,

3
0
0

m
g
5

m
g
/
k
g

(
m
a
x
.

3
0
0

m
g
)

d
a
i
l
y
1
0
-
1
5

m
g
/
k
g

(
m
a
x
.

3
0
0
m
g
)

d
a
i
l
y
A
s
y
m
p
t
o
m
a
t
i
c

e
l
e
v
a
t
i
o
n

o
f

a
m
i
n
o
t
r
a
n
s
f
e
r
a
s
e
s
S
a
f
e

i
n

p
r
e
g
n
a
n
c
y
E
x
c
e
l
l
e
n
t
P
a
t
i
e
n
t
s

w
i
t
h

p
r
e
e
x
i
s
t
i
n
g

l
i
v
e
r

d
i
s
e
a
s
e

o
r

S
y
r
u
p

(
1
0

m
g
/
m
L
)
1
5

m
g
/
k
g

(
m
a
x
.

9
0
0

m
g
)

1
x
/
w
k
,

2
x
/
w
k
,

o
r

3
x
/
w
k
2
0
-
3
0

m
g
/
k
g

(
m
a
x
.

9
0
0

m
g
)

2
x
/
w
k
C
l
i
n
i
c
a
l

h
e
p
a
t
i
t
i
s

(
b
u
t

r
i
s
k

o
f

h
e
p
a
t
i
t
i
s

i
n
c
r
e
a
s
e
d

a
b
n
o
r
m
a
l

l
i
v
e
r

f
u
n
c
t
i
o
n
:

p
e
r
f
o
r
m

l
i
v
e
r

f
u
n
c
t
i
o
n

I
M

I
n
j
e
c
t
i
o
n

(
1
0
0

m
g
/
m
L
)
F
a
t
a
l

h
e
p
a
t
i
t
i
s

d
u
r
i
n
g

p
e
r
i
p
a
r
t
u
m

p
e
r
i
o
d
)
.

t
e
s
t
s

m
o
n
t
h
l
y

a
n
d

w
h
e
n

s
y
m
p
t
o
m
s

o
c
c
u
r
.
P
e
r
i
p
h
e
r
a
l

n
e
u
r
o
t
o
x
i
c
i
t
y

(
d
o
s
e
-
r
e
l
a
t
e
d
)
P
y
r
i
d
o
x
i
n
e

s
u
p
p
l
e
m
e
n
t
a
i
o
n

(
2
5

m
g
/
d
a
y
)
M
e
a
s
u
r
e

s
e
r
u
m

c
o
n
c
e
n
t
r
a
t
i
o
n
s

o
f

P
H
E
N
Y
T
O
I
N
C
e
n
t
r
a
l

n
e
r
v
o
u
s

s
y
s
t
e
m

e
f
f
e
c
t
s

r
e
c
o
m
m
e
n
d
e
d

i
f

I
S
O
N
I
A
Z
I
D

a
n
d

C
A
R
B
A
M
A
Z
E
P
I
N
E

i
n

p
a
t
i
e
n
t
s

r
e
c
e
i
v
i
n
g

L
u
p
u
s
-
l
i
k
e

s
y
n
d
r
o
m
e

a
d
m
i
n
i
s
t
e
r
e
d

d
u
r
i
n
g

p
r
e
g
n
a
n
c
y
.

I
S
O
N
I
A
Z
I
D

w
i
t
h

o
r

w
i
t
h
o
u
t

R
I
F
A
M
P
I
N

a
n
d
H
y
p
e
r
s
e
n
s
i
t
i
v
i
t
y

r
e
a
c
t
i
o
n
s

(
r
a
r
e
)

a
d
j
u
s
t

d
o
s
e

i
f

n
e
c
e
s
s
a
r
y
.
M
o
n
o
a
m
i
n
e

(
h
i
s
t
a
m
i
n
e
/
t
y
r
a
m
i
n
e
)

p
o
i
s
o
n
i
n
g
D
i
a
r
r
h
e
a

(
i
f

S
O
R
B
I
T
O
L

i
n

I
S
O
N
I
A
Z
I
D

l
i
q
u
i
d
)
R
i
f
a
m
p
i
n
C
a
p
s
u
l
e
s

(
1
5
0

m
g
,

3
0
0

m
g
)
1
0

m
g
/
k
g

(
m
a
x
.

6
0
0

m
g
)

o
n
c
e

d
a
i
l
y
,

2
x
/
w
k
,

o
r

3
x
/
w
k
1
0
-
2
0

m
g
/
k
g

(
m
a
x
.

6
0
0

m
g
)

o
n
c
e

d
a
i
l
y
C
u
t
a
n
e
o
u
s

r
e
a
c
t
i
o
n
s
S
a
f
e

i
n

p
r
e
g
n
a
n
c
y
C
o
n
c
e
n
t
r
a
t
i
o
n
s

i
n
R
I
F
A
M
P
I
N

c
a
u
s
e
s

m
a
n
y

d
r
u
g

i
n
t
e
r
a
c
t
i
o
n
s

-
I
V

I
n
j
e
c
t
i
o
n

(
6
0
0

m
g
)

o
r

2
x
/
w
k
G
a
s
t
r
o
i
n
t
e
s
t
i
n
a
l

r
e
a
c
t
i
o
n
s

(
n
a
u
s
e
a
,

a
n
o
r
e
x
i
a
,

C
S
F

m
a
y

b
e

o
n
l
y

m
a
y

n
e
c
e
s
s
i
t
a
t
e

r
e
g
u
l
a
r

m
e
a
s
u
r
e
m
e
n
t
s

o
f

t
h
e

a
b
d
o
m
i
n
a
l

p
a
i
n
)

1
0
-
2
0
%

o
f

s
e
r
u
m

s
e
r
u
m

c
o
n
c
e
n
t
r
a
t
i
o
n
s

o
f

t
h
e

d
r
u
g
s

i
n

q
u
e
s
t
i
o
n
.
F
l
u
l
i
k
e

s
y
n
d
r
o
m
e

(
w
i
t
h

i
n
t
e
r
m
i
t
t
e
n
t
,

h
i
g
h

d
o
s
e
s
)

l
e
v
e
l
s
,

b
u
t

t
h
i
s

i
s
H
e
p
a
t
o
t
o
x
i
c
i
t
y

s
u
f
f
i
c
i
e
n
t

f
o
r

S
e
v
e
r
e

i
m
m
u
n
o
l
o
g
i
c

r
e
a
c
t
i
o
n
s

(
r
a
r
e
)

c
l
i
n
i
c
a
l

e
f
f
i
c
a
c
y
.
O
r
a
n
g
e

d
i
s
c
o
l
o
r
a
t
i
o
n

o
f

b
o
d
i
l
y

f
l
u
i
d
s

(
s
p
u
t
u
m
,
P
e
n
e
t
r
a
t
i
o
n

m
a
y

b
e

u
r
i
n
e
,

s
w
e
a
t
,

t
e
a
r
s
)

-

s
o
f
t

c
o
n
t
a
c
t

l
e
n
s
e
s

a
n
d

i
m
p
r
o
v
e
d

i
n

t
h
e

c
l
o
t
h
i
n
g

m
a
y

b
e

p
e
r
m
a
n
e
n
t
l
y

s
t
a
i
n
e
d
.

s
e
t
t
i
n
g

o
f

D
r
u
g

i
n
t
e
r
a
c
t
i
o
n
s

d
u
e

t
o

i
n
d
u
c
t
i
o
n

o
f

h
e
p
a
t
i
c

m
e
n
i
n
g
i
t
i
s
.

m
i
c
r
o
s
o
m
a
l

e
n
z
y
m
e
s
.

R
e
d
u
c
e
s

l
e
v
e
l
s

o
f

O
R
A
L

C
O
N
T
R
A
C
E
P
T
I
V
E
S
,

M
E
T
H
A
D
O
N
E
,

W
A
R
F
A
R
I
N
.

B
i
d
i
r
e
c
t
i
o
n
a
l

i
n
t
e
r
a
c
t
i
o
n
s

b
e
t
w
e
e
n

R
I
F
A
M
P
I
N

a
n
d

A
N
T
I
R
E
T
R
O
V
I
R
A
L

A
G
E
N
T
S
.
S
i
m
i
l
a
r

t
o

R
I
F
A
M
P
I
N
.
R
i
f
a
b
u
t
i
n
C
a
p
s
u
l
e
s

(
1
5
0

m
g
)
5

m
g
/
k
g

(
m
a
x
.

3
0
0

m
g
)

d
a
i
l
y
,

2
x
/
w
k
,

o
r

3
x
/
w
k
A
p
p
r
o
p
r
i
a
t
e

d
o
s
i
n
g

f
o
r

c
h
i
l
d
r
e
n

i
s
H
e
m
a
t
o
l
o
g
i
c

t
o
x
i
c
i
t
y

(
d
o
s
e
-
r
e
l
a
t
e
d

n
e
u
t
r
o
p
e
n
i
a
)
I
n
s
u
f
f
i
c
i
e
n
t

d
a
t
a

P
e
n
e
t
r
a
t
e
s
A
l
t
h
o
u
g
h

d
r
u
g

i
n
t
e
r
a
c
t
i
o
n
s

l
e
s
s

p
r
o
b
l
e
m
a
t
i
c
D
o
s
e

m
a
y

n
e
e
d

t
o

b
e

a
d
j
u
s
t
e
d

w
i
t
h

c
o
n
c
o
m
i
t
a
n
t

u
n
k
n
o
w
n
.
U
v
e
i
t
i
s

(
r
a
r
e

w
i
t
h

3
0
0
m
g

d
a
i
l
y

d
o
s
e
)
U
s
e

w
i
t
h

c
a
u
t
i
o
n

i
n

p
r
e
g
n
a
n
c
y

i
n
f
l
a
m
e
d

m
e
n
i
n
g
e
s
.

w
i
t
h

R
I
F
A
B
U
T
I
N
,

t
h
e
y

s
t
i
l
l

o
c
c
u
r

a
n
d

c
l
o
s
e

u
s
e

o
f

p
r
o
t
e
a
s
e

i
n
h
i
b
i
t
o
r
s

o
r

n
o
n
n
u
c
l
e
o
s
i
d
e
G
a
s
t
r
o
i
n
t
e
s
t
i
n
a
l

s
y
m
p
t
o
m
s

m
o
n
i
t
o
r
i
n
g

i
s

r
e
q
u
i
r
e
d
.

r
e
v
e
r
s
e

t
r
a
n
s
c
r
i
p
t
a
s
e

i
n
h
i
b
i
t
o
r
s
.
P
o
l
y
a
r
t
h
r
a
l
g
i
a
s
W
h
e
n

u
s
e
d

w
i
t
h

E
F
A
V
I
R
E
N
Z
,

t
h
e

d
o
s
e

o
f
H
e
p
a
t
o
t
o
x
i
c
i
t
y

R
I
F
A
B
U
T
I
N

s
h
o
u
l
d

b
e

i
n
c
r
e
a
s
e
d

t
o

4
5
0
-
6
0
0

m
g
P
s
e
u
d
o
j
a
u
n
d
i
c
e

(
s
k
i
n

d
i
s
c
o
l
o
r
a
t
i
o
n

w
i
t
h

d
a
i
l
y

o
r

i
n
t
e
r
m
i
t
t
e
n
t
l
y
.

n
o
r
m
a
l

b
i
l
i
r
u
b
i
n
)
R
a
s
h

(
r
a
r
e
)
F
l
u
l
i
k
e

s
y
n
d
r
o
m
e

(
r
a
r
e
)
O
r
a
n
g
e

d
i
s
c
o
l
o
r
a
t
i
o
n

o
f

b
o
d
i
l
y

f
l
u
i
d
s

(
s
p
u
t
u
m
,

u
r
i
n
e
,

s
w
e
a
t
,

t
e
a
r
s
)

-

s
o
f
t

c
o
n
t
a
c
t

l
e
n
s
e
s

a
n
d

c
l
o
t
h
i
n
g

m
a
y

b
e

p
e
r
m
a
n
e
n
t
l
y

s
t
a
i
n
e
d
.
S
e
r
u
m

u
r
i
c

a
c
i
d

m
e
a
s
u
r
e
m
e
n
t
s

n
o
t

P
y
r
a
z
i
n
a
m
i
d
e
T
a
b
l
e
t
s

(
5
0
0

m
g
)
P
a
t
i
e
n
t
s

4
0
-
5
5

k
g
:

1
,
0
0
0

m
g

d
a
i
l
y
,

1
,
5
0
0

m
g

3
x
/
w
k
,

1
5
-
3
0

m
g
/
k
g

(
m
a
x
.

2
,
0
0
0

m
g
)

d
a
i
l
y
H
e
p
a
t
o
t
o
x
i
c
i
t
y
L
i
t
t
l
e

i
n
f
o
r
m
a
t
i
o
n

a
v
a
i
l
a
b
l
e

o
n

s
a
f
e
t
y

P
a
s
s
e
s

f
r
e
e
l
y

i
n
t
o

r
e
c
o
m
m
e
n
d
e
d

a
s

a

r
o
u
t
i
n
e

b
u
t

m
a
y

s
e
r
v
e

a
s

o
r

2
,
0
0
0

m
g

2
x
/
w
k
5
0

m
g
/
k
g

(
m
a
x
.

4
,
0
0
0

m
g
)

2
x
/
w
k
G
a
s
t
r
o
i
n
t
e
s
t
i
n
a
l

s
y
m
p
t
o
m
s

(
n
a
u
s
e
a
,

v
o
m
i
t
i
n
g
)

i
n

p
r
e
g
n
a
n
c
y
.

t
h
e

C
S
F

-

a

s
u
r
r
o
g
a
t
e

m
a
r
k
e
r

f
o
r

c
o
m
p
l
i
a
n
c
e
.
P
a
t
i
e
n
t
s

5
6
-
7
5

k
g
:

1
,
5
0
0

m
g

d
a
i
l
y
,

2
,
5
0
0

m
g

3
x
/
w
k
,
N
o
n
g
o
u
t
y

p
o
l
y
a
r
t
h
r
a
l
g
i
a
W
H
O

a
n
d

I
U
A
T
L
D

r
e
c
o
m
m
e
n
d

c
o
n
c
e
n
t
r
a
t
i
o
n
s

L
i
v
e
r

c
h
e
m
i
s
t
r
y

m
o
n
i
t
o
r
i
n
g

r
e
c
o
m
m
e
n
d
e
d

i
f
:

o
r

3
,
0
0
0

m
g

2
x
/
w
k
A
s
y
m
p
t
o
m
a
t
i
c

h
y
p
e
r
u
r
i
c
e
m
i
a

P
Y
R
A
Z
I
N
A
M
I
D
E

f
o
r

u
s
e

i
n

p
r
e
g
n
a
n
t

e
q
u
i
v
a
l
e
n
t

t
o

t
h
o
s
e

u
s
e
d

w
i
t
h

R
I
F
A
M
P
I
N

i
n

t
r
e
a
t
i
n
g

l
a
t
e
n
t

T
B
,
P
a
t
i
e
n
t
s

7
6
-
9
0
+

k
g
:

2
,
0
0
0

m
g

d
a
i
l
y
,

3
,
0
0
0

m
g

3
x
/
w
k
,
A
c
u
t
e

g
o
u
t
y

a
r
t
h
r
i
t
i
s

(
a
v
o
i
d

P
Z
A

i
n

g
o
u
t

p
a
t
i
e
n
t
s
)

w
o
m
e
n

w
i
t
h

t
u
b
e
r
c
u
l
o
s
i
s
.

i
n

s
e
r
u
m
.

u
n
d
e
r
l
y
i
n
g

l
i
v
e
r

d
i
s
e
a
s
e

o
r

4
,
0
0
0

m
g

2
x
/
w
k

(
m
a
x
.

d
o
s
e
s

r
e
g
a
r
d
l
e
s
s

o
f

w
t
)
T
r
a
n
s
i
e
n
t

m
o
r
b
i
l
l
i
f
o
r
m

r
a
s
h
D
e
r
m
a
t
i
t
i
s

(
p
h
o
t
o
s
e
n
s
i
t
i
v
e

d
e
r
m
a
t
i
t
i
s
)
B
a
s
e
l
i
n
e

v
i
s
u
a
l

a
c
u
i
t
y

t
e
s
t
i
n
g

(
S
n
e
l
l
e
n

c
h
a
r
t
)

a
n
d
E
t
h
a
m
b
u
t
o
l
T
a
b
l
e
t
s

(
1
0
0

m
g
,

4
0
0

m
g
)
P
a
t
i
e
n
t
s

4
0
-
5
5

k
g
:

8
0
0

m
g

d
a
i
l
y
,

1
,
2
0
0

m
g

3
x
/
w
k
,
1
5
-
2
0

m
g
/
k
g

(
m
a
x
.

1
,
0
0
0

m
g
)

p
e
r

d
a
y
R
e
t
r
o
b
u
l
b
a
r

n
e
u
r
i
t
i
s

(
d
e
c
r
e
a
s
e
d

v
i
s
u
a
l

a
c
u
i
t
y

o
r
S
a
f
e

i
n

p
r
e
g
n
a
n
c
y
P
e
n
e
t
r
a
t
e
s

t
e
s
t
i
n
g

o
f

c
o
l
o
r

d
i
s
c
r
i
m
i
n
a
t
i
o
n

(
I
s
h
i
h
a
r
a

t
e
s
t
s
)
.

o
r

2
,
0
0
0

m
g

2
x
/
w
k
)
5
0

m
g
/
k
g

(
m
a
x
.

4
,
0
0
0

m
g
)

2
x
/
w
k

d
e
c
r
e
a
s
e
d

r
e
d
-
g
r
e
e
n

c
o
l
o
r

d
i
s
c
r
i
m
i
n
a
t
i
o
n
,

m
a
y

i
n
f
l
a
m
e
d

m
e
n
i
n
g
e
s
.
M
o
n
t
h
l
y

q
u
e
s
t
i
o
n
i
n
g

r
e
:

p
o
s
s
i
b
l
e

v
i
s
u
a
l

P
a
t
i
e
n
t
s

5
6
-
7
5

k
g
:

1
,
2
0
0

m
g

d
a
i
l
y
,

2
,
0
0
0

m
g

3
x
/
w
k
,
U
s
e

w
i
t
h

c
a
u
t
i
o
n

i
n

c
h
i
l
d
r
e
n

i
n

w
h
o
m

a
f
f
e
c
t

o
n
e

o
r

b
o
t
h

e
y
e
s
)
.

O
p
t
i
c

t
o
x
i
c
i
t
y

h
i
g
h
e
r
N
o

d
e
m
o
n
s
t
r
a
t
e
d

d
i
s
t
u
r
b
a
n
c
e
s

(
b
l
u
r
r
e
d

v
i
s
i
o
n

o
r

s
c
o
t
o
m
a
t
a
)
.

o
r

2
,
8
0
0

m
g

2
x
/
w
k

v
i
s
u
a
l

a
c
u
i
t
y

c
a
n
n
o
t

b
e

m
o
n
i
t
o
r
e
d

a
t

h
i
g
h
e
r

d
a
i
l
y

d
o
s
e
s

a
n
d

i
n

p
a
t
i
e
n
t
s

w
i
t
h

e
f
f
i
c
a
c
y

i
n

T
B
M
o
n
t
h
l
y

v
i
s
u
a
l

a
c
u
i
t
y

a
n
d

c
o
l
o
r

d
i
s
c
r
i
m
i
n
a
t
i
o
n
P
a
t
i
e
n
t
s

7
6
-
9
0
+
k
g
:

1
,
6
0
0

m
g

d
a
i
l
y
,

2
,
4
0
0

m
g

3
x
/
w
k
,

(
<

5

y
r
s

o
f

a
g
e
)

r
e
n
a
l

i
n
s
u
f
f
i
c
i
e
n
c
y
.

H
i
g
h
e
r

d
o
s
e
s

c
a
n

b
e

g
i
v
e
n

m
e
n
i
n
g
i
t
i
s
.

t
e
s
t
i
n
g

f
o
r

t
h
e

f
o
l
l
o
w
i
n
g

p
a
t
i
e
n
t
s
:

o
r

4
,
0
0
0

m
g

2
x
/
w
k

(
m
a
x
.

d
o
s
e
s

r
e
g
a
r
d
l
e
s
s

o
f

w
t
)
I
n

y
o
u
n
g
e
r

c
h
i
l
d
r
e
n
,

1
5
m
g
/
k
g

p
e
r

d
a
y

s
a
f
e
l
y

2
-
3
x
/
w
k
.

E
T
H
A
M
B
U
T
O
L

d
o
s
e

g
r
e
a
t
e
r

t
h
a
n

1
5
-
2
0

m
g
/
k
g
,

c
a
n

b
e

u
s
e

i
f

s
u
s
p
e
c
t
e
d

o
r

p
r
o
v
e
n
P
e
r
i
p
h
e
r
a
l

n
e
u
r
i
t
i
s

(
r
a
r
e
)

E
T
H
A
M
B
U
T
O
L

f
o
r

m
o
r
e

t
h
a
n

2

m
o
n
t
h
s
,

a
n
d

r
e
s
i
s
t
a
n
c
e

t
o

I
N
H

o
r

R
I
F
C
u
t
a
n
e
o
u
s

r
e
a
c
t
i
o
n
s

a
n
y

p
a
t
i
e
n
t

w
i
t
h

r
e
n
a
l

i
n
s
u
f
f
i
c
i
e
n
c
y
.
I
n
s
t
r
u
c
t

p
a
t
i
e
n
t

t
o

c
o
n
t
a
c
t

t
h
e
i
r

p
h
y
s
i
c
i
a
n

o
r

p
u
b
l
i
c

h
e
a
l
t
h

c
l
i
n
i
c

i
m
m
e
d
i
a
t
e
l
y

i
f

t
h
e
y

e
x
p
e
r
i
e
n
c
e

a

c
h
a
n
g
e

i
n

v
i
s
i
o
n
.
E
T
H
A
M
B
U
T
O
L

s
h
o
u
l
d

b
e

d
i
s
c
o
n
t
i
n
u
e
d

i
m
m
e
d
i
a
t
e
l
y

a
n
d

p
e
r
m
a
n
e
n
t
l
y

i
f

a
n
y

s
i
g
n
s

o
f

v
i
s
u
a
l

t
o
x
i
c
i
t
y
.
1
.

A
m
e
r
i
c
a
n

T
h
o
r
a
c
i
c

S
o
c
i
e
t
y
,

e
t

a
l
.

"
T
r
e
a
t
m
e
n
t

o
f

T
u
b
e
r
c
u
l
o
s
i
s
.
"

A
m
e
r
i
c
a
n

J
o
u
r
n
a
l

o
f

R
e
s
p
i
r
a
t
o
r
y

a
n
d

C
r
i
t
a
l

C
a
r
e

M
e
d
i
c
i
n
e

1
6
7

(
2
0
0
3
)
:

6
0
3
-
6
6
2
.
R
e
f
e
r
e
n
c
e
s
:

7
4
T
a
b
l
e

2
:

S
e
c
o
n
d
-
L
i
n
e

D
r
u
g
s

f
o
r

T
u
b
e
r
c
u
l
o
s
i
s

T
r
e
a
t
m
e
n
t
1
D
r
u
g
P
r
e
p
a
r
a
t
i
o
n
s
A
d
u
l
t
s
C
h
i
l
d
r
e
n
A
d
v
e
r
s
e

E
f
f
e
c
t
s
U
s
e

i
n

P
r
e
g
n
a
n
c
y
C
N
S

P
e
n
e
t
r
a
t
i
o
n
M
o
n
i
t
o
r
i
n
g
C
y
c
l
o
s
e
r
i
n
e
C
a
p
s
u
l
e
s

(
2
5
0

m
g
)
1
0
-
1
5

m
g
/
k
g

p
e
r

d
a
y

(
m
a
x

1
0
0
0

m
g
/
d
a
y

i
n

2

d
o
s
e
s
)
,

1
0
-
1
5

m
g
/
k
g

p
e
r

d
a
y

(
m
a
x
.

1
,
0
0
0

m
g
/
d
a
y
)
C
e
n
t
r
a
l

n
e
r
v
o
u
s

s
y
s
t
e
m

e
f
f
e
c
t
s

(
r
a
n
g
e
s

f
r
o
m

C
r
o
s
s
e
s

t
h
e

p
l
a
c
e
n
t
a
.
C
S
F

c
o
n
c
e
n
t
r
a
t
i
o
n
s
N
e
u
r
o
p
s
y
c
h
i
a
t
r
i
c

s
t
a
t
u
s

s
h
o
u
l
d

b
e
(
f
o
r

p
a
t
i
e
n
t
s

w
i
t
h
:
u
s
u
a
l
l
y

5
0
0
-
7
5
0

m
g
/
d
a
y

g
i
v
e
n

i
n

2

d
o
s
e
s
.
m
i
l
d

r
e
a
c
t
i
o
n
s
,

s
u
c
h

a
s

h
e
a
d
a
c
h
e
s

o
r

r
e
s
t
l
e
s
s
n
e
s
s
,
L
i
m
i
t
e
d

d
a
t
a

o
n

s
a
f
e
t
y

i
n

a
p
p
r
o
a
c
h

t
h
o
s
e

i
n
a
s
s
e
s
s
e
d

a
t

l
e
a
s
t

a
t

m
o
n
t
h
l
y

d
r
u
g
-
r
e
s
i
s
t
a
n
t

T
B
,

o
r
T
o
x
i
c
i
t
y

i
s

m
o
r
e

c
o
m
m
o
n

a
t

d
o
s
e
s

o
v
e
r

5
0
0

m
g
/
d
a
y
.
t
o

s
e
v
e
r
e

r
e
a
c
t
i
o
n
s
,

s
u
c
h

a
s

p
s
y
c
h
o
s
i
s

i
n

p
r
e
g
n
a
n
c
y

-

s
h
o
u
l
d

b
e

s
e
r
u
m
.
i
n
t
e
r
v
a
l
s

a
n
d

m
o
r
e

f
r
e
q
u
e
n
t
l
y

i
f

a
c
u
t
e

h
e
p
a
t
i
t
i
s

-

i
n
a
n
d

s
e
i
z
u
r
e
s
)
.
u
s
e
d

i
n

p
r
e
g
n
a
n
t

w
o
m
e
n
s
y
m
p
t
o
m
s

d
e
v
e
l
o
p
.

c
o
m
b
i
n
a
t
i
o
n

w
i
t
h

o
t
h
e
r

T
o
x
i
c
i
t
y

m
o
r
e

c
o
m
m
o
n

a
t

d
o
s
e
s

o
v
e
r

5
0
0

m
g
/
d
a
y
.
o
n
l
y

w
h
e
n

t
h
e
r
e

a
r
e

n
o

S
e
r
u
m

c
o
n
c
e
n
t
r
a
t
i
o
n

n
o
n
h
e
p
a
t
o
t
o
x
i
c

d
r
u
g
s
)
P
Y
R
I
D
O
X
I
N
E

m
a
y

h
e
l
p

p
r
e
v
e
n
t

a
n
d

t
r
e
a
t

n
e
u
r
o
t
o
x
i
c

s
u
i
t
a
b
l
e

a
l
t
e
r
n
a
t
i
v
e
s
.
m
e
a
s
u
r
e
m
e
n
t
s

m
a
y

b
e

s
i
d
e

e
f
f
e
c
t
s

a
n
d

i
s

u
s
u
a
l
l
y

g
i
v
e
n

i
n

a

d
o
s
a
g
e

o
f

n
e
c
e
s
s
a
r
y

u
n
t
i
l

a
n

a
p
p
r
o
p
r
i
a
t
e

1
0
0
-
2
0
0

m
g
/
d
a
y
.
d
o
s
e

i
s

e
s
t
a
b
l
i
s
t
e
d
.
C
o
n
t
r
a
i
n
d
i
c
a
t
e
d

i
n

e
p
i
l
e
p
t
i
c
s
.
P
a
t
i
e
n
t
s

t
a
k
i
n
g

P
H
E
N
Y
T
O
I
N
:
s
e
r
u
m

c
o
n
c
e
n
t
r
a
t
i
o
n
s

o
f

P
H
E
N
Y
T
O
I
N

s
h
o
u
l
d

b
e

m
e
a
s
u
r
e
d
.
E
t
h
i
o
n
a
m
i
d
e
T
a
b
l
e
t
s

(
2
5
0

m
g
)
1
5
-
2
0

m
g
/
k
g

p
e
r

d
a
y

(
m
a
x

1
0
0
0

m
g
/
d
a
y
)
,
1
5
-
2
0

m
g
/
k
g

p
e
r

d
a
y

(
m
a
x

1
,
0
0
0

m
g
/
d
a
y
)
G
a
s
t
r
o
i
n
t
e
s
t
i
n
a
l

e
f
f
e
c
t
s

(
m
e
t
a
l
l
i
c

t
a
s
t
e
,

n
a
u
s
e
a
,
C
r
o
s
s
e
s

t
h
e

p
l
a
c
e
n
t
a
.
C
S
F

c
o
n
c
e
n
t
r
a
t
i
o
n
s
L
i
v
e
r

f
u
n
c
t
i
o
n

t
e
s
t
s

s
h
o
u
l
d

b
e
(
f
o
r

p
a
t
i
e
n
t
s

w
i
t
h

d
r
u
g
-
u
s
u
a
l
l
y

5
0
0
-
7
5
0

m
g
/
d
a
y

i
n

a

s
i
n
g
l
e

d
a
i
l
y

d
o
s
e

o
r
v
o
m
i
t
i
n
g

[
o
f
t
e
n

s
e
v
e
r
e
]
,

l
o
s
s

o
f

a
p
p
e
t
i
t
e
,

a
b
d
o
m
i
n
a
l
T
e
r
a
t
o
g
e
n
i
c

i
n

a
n
i
m
a
l
s
.
e
q
u
a
l

t
o

t
h
o
s
e

i
n

o
b
t
a
i
n
e
d

a
t

b
a
s
e
l
i
n
e
,

a
n
d

i
f
r
e
s
i
s
t
a
n
t

T
B
)
t
w
o

d
i
v
i
d
e
d

d
o
s
e
s
.
p
a
i
n
)

-

s
y
m
p
t
o
m
s

m
a
y

i
m
p
r
o
v
e

i
f

d
o
s
e
s

t
a
k
e
n

w
i
t
h
S
h
o
u
l
d

n
o
t

b
e

u
s
e
d

i
n
s
e
r
u
m
.
u
n
d
e
r
l
y
i
n
g

l
i
v
e
r

d
i
s
e
a
s
e
,

a
t
T
h
e

s
i
n
g
l
e

d
a
i
l
y

d
o
s
e

c
a
n

b
e

g
i
v
e
n

a
t

b
e
d
t
i
m
e

o
r
f
o
o
d

o
r

a
t

b
e
d
t
i
m
e
.
p
r
e
g
n
a
n
c
y
.
m
o
n
t
h
l
y

i
n
t
e
r
v
a
l
s
.

R
e
p
e
a
t

i
f
w
i
t
h

t
h
e

m
a
i
n

m
e
a
l
.
H
e
p
a
t
o
t
o
x
i
c
i
t
y
s
y
m
p
t
o
m
s

o
c
c
u
r
.
N
e
u
r
o
t
o
x
i
c
i
t
y

(
p
e
r
i
p
h
e
r
a
l

n
e
u
r
i
t
i
s
,

o
p
t
i
c

n
e
u
r
i
t
i
s
,
T
h
y
r
o
i
d
-
s
t
i
m
u
l
a
t
i
n
g

h
o
r
m
o
n
e
a
n
x
i
e
t
y
,

d
e
p
r
e
s
s
i
o
n
,

p
s
y
c
h
o
s
i
s
)
s
h
o
u
l
d

b
e

m
e
a
s
u
r
e
d

a
t

b
a
s
e
l
i
n
e
E
n
d
o
c
r
i
n
e

e
f
f
e
c
t
s

(
g
y
n
e
c
o
m
a
s
t
i
a
,

a
l
o
p
e
c
i
a
,

a
n
d

a
t

m
o
n
t
h
l
y

i
n
t
e
r
v
a
l
s
.
h
y
p
o
t
h
y
r
o
i
d
i
s
m
,

i
m
p
o
t
e
n
c
e
)
D
i
a
b
e
t
e
s

m
a
y

b
e

m
o
r
e

d
i
f
f
i
c
u
l
t

t
o

m
a
n
a
g
e

i
n
p
a
t
i
e
n
t
s

t
a
k
i
n
g

E
T
H
I
O
N
A
M
I
D
E
.
S
t
r
e
p
t
o
m
y
c
i
n
I
M

i
n
j
e
c
t
i
o
n

(
1

g
r
a
m

p
e
r

v
i
a
l
)
1
5

m
g
/
k
g

p
e
r

d
a
y

(
m
a
x

1
0
0
0

m
g
/
d
a
y
)

I
M

o
r

I
V
,
2
0
-
4
0

m
g
/
k
g

p
e
r

d
a
y

(
m
a
x

1
,
0
0
0

m
g
/
d
a
y
)
O
t
o
t
o
x
i
c
i
t
y

(
v
e
s
t
i
b
u
l
a
r

a
n
d

h
e
a
r
i
n
g

d
i
s
t
u
r
b
a
n
c
e
s
)

-
C
o
n
t
r
a
i
n
d
i
c
a
t
e
d

i
n

O
n
l
y

s
l
i
g
h
t

d
i
f
f
u
s
i
o
n

P
e
r
f
o
r
m

a
u
d
i
o
g
r
a
m
,

v
e
s
t
i
b
u
l
a
r

u
s
u
a
l
l
y

g
i
v
e
n

a
s

a

s
i
n
g
l
e

d
a
i
l
y

d
o
s
e

(
5
-
7

d
a
y
s
/
w
e
e
k
)

2
0

m
g
/
k
g

2
x
/
w
k
r
i
s
k

i
n
c
r
e
a
s
e
d

w
i
t
h

a
g
e

o
r

c
o
n
c
o
m
i
t
a
n
t

u
s
e

o
f
p
r
e
g
n
a
n
c
y

b
e
c
a
u
s
e

o
f

i
n
t
o

C
S
F
,

e
v
e
n

i
n

t
e
s
t
i
n
g
,

R
o
m
b
e
r
g

t
e
s
t
i
n
g
,

a
n
d
i
n
i
t
i
a
l
l
y

I
M

o
r

I
V

g
i
v
e
n

a
s

a

s
i
n
g
l
e

d
o
s
e

5
-
7

d
a
y
s
/
w
e
e
k
,
l
o
o
p
-
i
n
h
i
b
i
t
i
n
g

d
i
u
r
e
t
i
c
s

(
F
U
R
O
S
E
M
I
D
E
,

t
h
e

r
i
s
k

o
f

f
e
t
a
l

h
e
a
r
i
n
g
p
a
t
i
e
n
t
s

w
i
t
h

s
e
r
u
m

c
r
e
a
t
i
n
i
n
e

m
e
a
s
u
r
e
m
e
n
t
r
e
d
u
c
e
d

t
o

2
-
3
x
/
w
k

a
f
t
e
r

t
h
e

f
i
r
s
t

2
-
4

m
o
n
t
h
s
E
T
H
A
C
R
Y
N
I
C

A
C
I
D
)

a
n
d

w
i
t
h

i
n
c
r
e
a
s
i
n
g

s
i
n
g
l
e

l
o
s
s
.
m
e
n
i
n
g
i
t
i
s
.
a
t

b
a
s
e
l
i
n
e
.
o
r

a
f
t
e
r

c
u
l
t
u
r
e

c
o
n
v
e
r
s
i
o
n
,

d
e
p
e
n
d
i
n
g

o
n

t
h
e
d
o
s
e
s

a
n
d

c
u
m
u
l
a
t
i
v
e

d
o
s
e

(
e
s
p
.

a
b
o
v
e

1
0
0
-
1
2
0

g
)
.
A
s
s
e
s
s

r
e
n
a
l

f
u
n
c
t
i
o
n
,

a
n
d

e
f
f
i
c
a
c
y

o
f

t
h
e

o
t
h
e
r

d
r
u
g
s

i
n

t
h
e

r
e
g
i
m
e
n
.
N
e
u
r
o
t
o
x
i
c
i
t
y

(
c
i
r
c
u
m
o
r
a
l

p
a
r
a
s
t
h
e
s
i
a
s

i
m
m
e
d
i
a
t
e
l
y
q
u
e
s
t
i
o
n

r
e
g
a
r
d
i
n
g

a
u
d
i
t
o
r
y

o
r
P
a
t
i
e
n
t
s

o
v
e
r

5
9

y
e
a
r
s

o
f

a
g
e
:

1
0

m
g
/
k
g

p
e
r

d
a
y

a
f
t
e
r

i
n
j
e
c
t
i
o
n
.

R
a
r
e
l
y
,

m
a
y

i
n
t
e
r
a
c
t

w
i
t
h

m
u
s
c
l
e
v
e
s
t
i
b
u
l
a
r

s
y
m
p
t
o
m
s

m
o
n
t
h
l
y
.
(
m
a
x
.

7
5
0

m
g

p
e
r

d
a
y
)
.
r
e
l
a
x
a
n
t
s

t
o

c
a
u
s
e

p
o
s
t
o
p
e
r
a
t
i
v
e

r
e
s
p
i
r
a
t
o
r
y

R
e
p
e
a
t

a
u
d
i
o
g
r
a
m

a
n
d

v
e
s
t
i
b
u
l
a
r
P
a
t
i
e
n
t
s

w
i
t
h

r
e
n
a
l

i
n
s
u
f
f
i
c
i
e
n
c
y
:

1
2
-
1
5

m
g
/
k
g

p
e
r
m
u
s
c
l
e

w
e
a
k
n
e
s
s
.
)
t
e
s
t
i
n
g

i
f

s
y
m
p
t
o
m
s

o
f

8
t
h

d
o
s
e

2
-
3
x
/
w
k
.

(
d
o
s
i
n
g

f
r
e
q
u
e
n
c
y

r
e
d
u
c
e
d
)
.
N
e
p
h
r
o
t
o
x
i
c
i
t
y

(
l
e
s
s

c
o
m
m
o
n

w
i
t
h

c
r
a
n
i
a
l

n
e
r
v
e

t
o
x
i
c
i
t
y
.
M
o
n
i
t
e
r

s
e
r
u
m

d
r
u
g

l
e
v
e
l
s

t
o

a
v
o
i
d

t
o
x
i
c
i
t
y
.
S
T
R
E
P
T
O
M
Y
C
I
N

t
h
a
n

w
i
t
h

A
M
I
K
A
C
I
N
,
K
A
N
A
M
Y
C
I
N
,

o
r

C
A
P
R
E
O
M
Y
C
I
N
)

A
m
i
k
a
c
i
n

/

K
a
n
a
m
y
c
i
n
A
m
i
k
a
c
i
n
:

I
M

o
r

I
V

i
n
j
e
c
t
i
o
n
1
5

m
g
/
k
g

p
e
r

d
a
y

(
m
a
x

1
0
0
0

m
g
/
d
a
y
)

I
M

o
r

I
V
,
1
5
-
3
0

m
g
/
k
g

p
e
r

d
a
y

(
m
a
.

1
,
0
0
0

m
g
/
d
a
y
)
O
t
o
t
o
x
i
c
i
t
y
:

m
a
y

c
a
u
s
e

d
e
a
f
n
e
s
s
,

l
e
s
s

v
e
s
t
i
b
u
l
a
r
C
o
n
t
r
a
i
n
d
i
c
a
t
e
d

i
n

O
n
l
y

l
o
w

c
o
n
c
e
n
t
r
a
-
M
o
n
i
t
o
r

a
s

w
i
t
h

S
t
r
e
p
t
o
m
y
c
i
n
.
(
m
o
s
t

S
t
r
e
p
t
o
m
y
c
i
n
-
r
e
s
i
s
t
a
n
t

(
5
0
0

m
g

p
e
r

2

m
L

v
i
a
l
)
u
s
u
a
l
l
y

g
i
v
e
n

a
s

a

s
i
n
g
l
e

d
a
i
l
y

d
o
s
e

7
5
0
-
1
0
0

m
g

I
M

o
r

I
V
,

a
s

a

s
i
n
g
l
e

d
a
i
l
y

d
o
s
e
.
d
y
s
f
u
n
c
t
i
o
n

t
h
a
n

S
T
R
E
P
T
O
M
Y
C
I
N
.

M
o
r
e

c
o
m
m
o
n
p
r
e
g
n
a
n
t

w
o
m
e
n

t
i
o
n
s

f
o
u
n
d

i
n

C
S
F
.
A
m
i
k
a
c
i
n

s
e
r
u
m

c
o
n
c
e
n
t
r
a
t
i
o
n
s
s
t
r
a
i
n
s

a
r
e

s
u
s
c
e
p
t
i
b
l
e
K
a
n
a
m
y
c
i
n
:
I
M

o
r

I
V

i
n
j
e
c
t
i
o
n

(
5
-
7

d
a
y
s
/
w
e
e
k
)

i
n
i
t
i
a
l
l
y
,

t
h
e
n

r
e
d
u
c
e

t
o

2
-
3
x
/
w
k
w
i
t
h

c
o
n
c
u
r
r
e
n
t

u
s
e

o
f

d
i
u
r
e
t
i
c
s
.
b
e
c
a
u
s
e

o
f

r
i
s
k

o
f

f
e
t
a
l

S
l
i
g
h
t
l
y

h
i
g
h
e
r

c
a
n

b
e

o
b
t
a
i
n
e
d

r
o
u
t
i
n
e
l
y
.
t
o

b
o
t
h
)

(
1

g
r
a
m

p
e
r

v
i
a
l
)
a
f
t
e
r

t
h
e

f
i
r
s
t

2
-
4

m
o
n
t
h
s

o
r

a
f
t
e
r

c
u
l
t
u
r
e

c
o
n
v
e
r
s
i
o
n
,

1
5
-
3
0

m
g
/
k
g

2
x
/
w
k
N
e
p
h
r
o
t
o
x
i
c
i
t
y
:

m
o
r
e

n
e
p
h
r
o
t
o
x
i
c

t
h
a
n

n
e
p
h
r
o
t
o
x
i
c
i
t
y

a
n
d

c
o
n
c
e
n
t
r
a
t
i
o
n
s

i
n
P
a
t
i
e
n
t
s

w
i
t
h

s
e
v
e
r
e

h
e
p
a
t
i
c

d
e
p
e
n
d
i
n
g

o
n

t
h
e

e
f
f
i
c
a
c
y

o
f

t
h
e

o
t
h
e
r

d
r
u
g
s

i
n

S
T
R
E
P
T
O
M
Y
C
I
N
.

H
i
g
h
e
r

f
r
e
q
u
e
n
c
y

i
n

p
a
t
i
e
n
t
s
:
c
o
n
g
e
n
i
t
a
l

h
e
a
r
i
n
g

l
o
s
s
.
t
h
e

p
r
e
s
e
n
c
e

o
f

d
i
s
e
a
s
e

m
a
y

b
e

a
t

g
r
e
a
t
e
r

r
i
s
k

t
h
e

r
e
g
i
m
e
n
.
P
a
t
i
e
n
t
s

o
v
e
r

5
9

y
e
a
r
s

o
f

a
g
e
:

1
0

m
g
/
k
g

p
e
r

d
a
y

w
i
t
h

i
n
i
t
i
a
l
l
y

i
n
c
r
e
a
s
e
d

c
r
e
a
t
i
n
i
n
e

l
e
v
e
l
s
,
m
e
n
i
n
g
i
t
i
s
.
f
o
r

n
e
p
h
r
o
t
o
x
i
c
i
t
y

-

s
h
o
u
l
d

h
a
v
e

(
m
a
x
.

7
5
0

m
g

p
e
r

d
a
y
)
.

r
e
c
e
i
v
i
n
g

l
a
r
g
e
r

t
o
t
a
l

d
o
s
e
s
r
e
n
a
l

f
u
n
c
t
i
o
n

m
o
n
i
t
o
r
e
d

c
l
o
s
e
l
y
P
a
t
i
e
n
t
s

w
i
t
h

r
e
n
a
l

i
n
s
u
f
f
i
c
i
e
n
c
y
:

1
2
-
1
5

m
g
/
k
g

p
e
r

r
e
c
e
i
v
i
n
g

o
t
h
e
r

n
e
p
h
r
o
t
o
x
i
c

a
g
e
n
t
s
(
b
e
c
a
u
s
e

o
f

p
r
e
d
i
s
p
o
s
i
t
i
o
n

t
o

d
o
s
e

2
-
3
x
/
w
k
.

(
d
o
s
i
n
g

f
r
e
q
u
e
n
c
y

r
e
d
u
c
e
d
)
h
e
p
a
t
o
-
r
e
n
a
l

s
y
n
d
r
o
m
e
)
.
7
5
T
a
b
l
e

2
:

S
e
c
o
n
d
-
L
i
n
e

D
r
u
g
s

f
o
r

T
u
b
e
r
c
u
l
o
s
i
s

T
r
e
a
t
m
e
n
t

1
(
c
o
n
t
i
n
u
e
d
)
D
r
u
g
P
r
e
p
a
r
a
t
i
o
n
s
A
d
u
l
t
s
C
h
i
l
d
r
e
n
A
d
v
e
r
s
e

E
f
f
e
c
t
s
U
s
e

i
n

P
r
e
g
n
a
n
c
y
C
N
S

P
e
n
e
t
r
a
t
i
o
n
M
o
n
i
t
o
r
i
n
g
C
a
p
r
e
o
m
y
c
i
n
I
M

o
r

I
V

i
n
j
e
c
t
i
o
n

(
1

g
r
a
m

p
e
r

1
5

m
g
/
k
g

p
e
r

d
a
y

(
m
a
x

1
0
0
0

m
g
/
d
a
y
)

I
M

o
r

I
V
,
1
5
-
3
0

m
g
/
k
g

p
e
r

d
a
y

(
m
a
x
.

1
,
0
0
0

m
g
/
d
a
y
)
N
e
p
h
r
o
t
o
x
i
c
i
t
y
:

m
a
y

r
e
s
u
l
t

i
n

r
e
d
u
c
e
d

c
r
e
a
t
i
n
i
n
e
A
v
o
i
d

i
n

p
r
e
g
n
a
n
c
y

D
o
e
s

n
o
t

p
e
n
e
t
r
a
t
e

M
o
n
i
t
o
r

a
s

w
i
t
h

S
t
r
e
p
t
o
m
y
c
i
n
.
(
f
o
r

p
a
t
i
e
n
t
s

w
i
t
h

d
r
u
g
-
v
i
a
l
)
u
s
u
a
l
l
y

g
i
v
e
n

a
s

a

s
i
n
g
l
e

(
7
5
0
-
1
0
0
0

m
g
)

d
a
i
l
y

d
o
s
e

I
M

o
r

I
V
,

a
s

a

s
i
n
g
l
e

d
a
i
l
y

d
o
s
e

o
r

2
x
/
w
k
.
c
l
e
a
r
a
n
c
e

o
r

p
o
t
a
s
s
i
u
m

a
n
d

m
a
g
n
e
s
i
u
m

d
e
p
l
e
t
i
o
n
.
b
e
c
a
u
s
e

o
f

r
i
s
k

o
f

f
e
t
a
l
i
n
t
o

t
h
e

C
S
F
.
S
e
r
u
m

p
o
t
a
s
s
i
u
m

a
n
d

m
a
g
n
e
s
i
u
m
r
e
s
i
s
t
a
n
t

T
B
)
(
5
-
7

d
a
y
s
/
w
e
e
k
)

i
n
i
t
i
a
l
l
y
,

t
h
e
n

r
e
d
u
c
e

t
o

2
-
3
x
/
w
k
P
r
o
t
e
i
n
u
r
i
a

c
o
m
m
o
n
.
n
e
p
h
r
o
t
o
x
i
c
i
t
y

a
n
d

c
o
n
c
e
n
t
r
a
t
i
o
n
s

s
h
o
u
l
d

b
e
a
f
t
e
r

t
h
e

f
i
r
s
t

2
-
4

m
o
n
t
h
s

o
r

a
f
t
e
r

c
u
l
t
u
r
e

c
o
n
v
e
r
s
i
o
n
,

O
t
o
t
o
x
i
c
i
t
y
:

v
e
s
t
i
b
u
l
a
r

d
i
s
t
u
r
b
a
n
c
e
s
,

t
i
n
n
i
t
u
s
,

a
n
d
c
o
n
g
e
n
i
t
a
l

h
e
a
r
i
n
g

l
o
s
s
.
m
e
a
s
u
r
e
d

a
t

b
a
s
e
l
i
n
e

a
n
d

a
t

d
e
p
e
n
d
i
n
g

o
n

t
h
e

e
f
f
i
c
a
c
y

o
f

t
h
e

o
t
h
e
r

d
r
u
g
s
d
e
a
f
n
e
s
s

-

m
o
r
e

f
r
e
q
u
e
n
t

i
n

e
l
d
e
r
l
y

p
a
t
i
e
n
t
s

a
n
d

l
e
a
s
t

a
t

m
o
n
t
h
l
y

i
n
t
e
r
v
a
l
s
.
i
n

t
h
e

r
e
g
i
m
e
n
.
p
a
t
i
e
n
t
s

w
i
t
h

p
r
e
-
e
x
i
s
t
i
n
g

r
e
n
a
l

i
m
p
a
i
r
m
e
n
t
.
P
a
t
i
e
n
t
s

o
v
e
r

5
9

y
e
a
r
s

o
f

a
g
e
:

1
0

m
g
/
k
g

p
e
r

d
a
y

(
m
a
x
.

7
5
0

m
g

p
e
r

d
a
y
)
.
P
a
t
i
e
n
t
s

w
i
t
h

r
e
n
a
l

i
n
s
u
f
f
i
c
i
e
n
c
y
:

1
2
-
1
5

m
g
/
k
g

p
e
r

d
o
s
e

2
-
3
x
/
w
k
.

(
d
o
s
i
n
g

f
r
e
q
u
e
n
c
y

r
e
d
u
c
e
d
)
p
-
A
m
i
n
o
s
a
l
i
c
y
l
i
c

A
c
i
d

(
P
A
S
)
4

g
r
a
m

p
a
c
k
e
t
s

(
P
a
s
e
r
8
-
1
2

g
r
a
m
s

p
e
r

d
a
y

i
n

2
-
3

d
i
v
i
d
e
d

d
o
s
e
s
.
2
0
0
-
3
0
0

m
g
/
k
g

p
e
r

d
a
y

i
n

2
-
4

d
i
v
i
d
e
d
H
e
p
a
t
o
t
o
x
i
c
i
t
y
N
o

s
t
u
d
i
e
s

i
n

h
u
m
a
n
s
.
I
n
f
l
a
m
e
d

m
e
n
i
n
g
e
s
:
H
e
p
a
t
i
c

e
n
z
y
m
e
s

a
n
d

t
h
y
r
o
i
d

(
f
o
r

p
a
t
i
e
n
t
s

w
i
t
h

d
r
u
g
-
G
r
a
n
u
l
e
s
)
U
s
u
a
l

d
o
s
e

o
f

P
A
S

G
r
a
n
u
l
e
s
:

4

g
r
a
m
s

T
I
D
.
d
o
s
e
s
.
G
a
s
t
r
o
i
n
t
e
s
t
i
n
a
l

d
i
s
t
r
e
s
s
:

m
o
s
t

c
o
m
m
o
n

s
i
d
e

e
f
f
e
c
t
P
A
S

h
a
s

b
e
e
n

u
s
e
d

c
o
n
c
e
n
t
r
a
t
i
o
n
s
f
u
n
c
t
i
o
n

s
h
o
u
l
d

b
e

m
e
a
s
u
r
e
d

a
t
r
e
s
i
s
t
a
n
t

T
B
)
H
o
w
e
v
e
r
,

i
t

h
a
s

b
e
e
n

s
h
o
w

t
h
a
t

4

g
r
a
m
s

B
I
D

i
s

o
f

P
A
S
.

L
e
s
s

w
i
t
h

l
o
w
e
r

d
o
s
e
s

(
8

g
r
a
m
s

d
a
i
l
y
)

s
a
f
e
l
y

i
n

p
r
e
g
n
a
n
c
y
.
b
e
t
w
e
e
n

1
0
-
5
0
%
b
a
s
e
l
i
n
e
.
a
d
e
q
u
a
t
e

t
o

a
c
h
i
e
v
e

t
a
r
g
e
t

s
e
r
u
m

c
o
n
c
e
n
t
r
a
t
i
o
n
.
a
n
d

w
i
t
h

t
h
e

g
r
a
n
u
l
a
r

f
o
r
m
u
l
a
t
i
o
n

o
f

t
h
e

d
r
u
g
.
S
h
o
u
l
d

b
e

u
s
e
d

o
n
l
y

i
f
o
f

t
h
o
s
e

i
n

s
e
r
u
m
.
P
r
o
l
o
n
g
e
d

t
h
e
r
a
p
y

(
>

3

m
o
n
t
h
s
)
:
M
a
l
a
b
s
o
r
p
t
i
o
n

s
y
n
d
r
o
m
e
:

s
t
e
a
t
o
r
r
h
e
a
,

l
o
w

s
e
r
u
m
t
h
e
r
e

a
r
e

n
o

a
l
t
e
r
n
a
t
i
v
e
s
M
a
r
g
i
n
a
l

e
f
f
i
c
a
c
y

i
n
t
h
y
r
o
i
d

f
u
n
c
t
i
o
n

s
h
o
u
l
d

b
e

f
o
l
a
t
e

l
e
v
e
l
s
.
f
o
r

a

p
r
e
g
n
a
n
t

w
o
m
a
n

m
e
n
i
n
g
i
t
i
s
.
c
h
e
c
k
e
d

e
v
e
r
y

3

m
o
n
t
h
s
.
H
y
p
o
t
h
y
r
o
i
d
i
s
m
:

c
o
m
m
o
n

s
i
d
e

e
f
f
e
c
t
,

e
s
p
e
c
i
a
l
l
y

w
i
t
h

m
u
l
t
i
d
r
u
g
-
r
e
s
i
s
t
a
n
t

.
w
i
t
h
p
r
o
l
o
n
g
e
d

a
d
m
i
n
i
s
t
r
a
t
i
o
n

o
r

c
o
n
c
o
m
i
t
a
n
t

u
s
e

T
B
o
f

e
t
h
i
o
n
a
m
i
d
e
.

M
a
y

b
e

a
c
c
o
m
p
a
n
i
e
d

b
y

g
o
i
t
e
r

f
o
r
m
a
t
i
o
n
.

T
h
y
r
o
i
d

h
o
r
m
o
n
e

r
e
p
l
a
c
e
m
e
n
t

m
a
y

b
e
r
e
q
u
i
r
e
d
.

T
h
y
r
o
i
d

f
u
n
c
t
i
o
n
s

r
e
t
u
r
n
s

t
o

n
o
r
m
a
l

a
f
t
e
r
d
i
s
c
o
n
t
i
n
u
a
t
i
o
n

o
f

d
r
u
g
.
C
o
a
g
u
l
o
p
a
t
h
y
:

d
o
u
b
l
i
n
g

o
f

p
r
o
t
h
r
o
m
b
i
n

t
i
m
e

-

l
e
s
s
e
n
e
d

b
y

c
o
a
d
m
i
n
i
s
t
r
a
t
i
o
n

o
f

s
t
r
e
p
t
o
m
y
c
i
n
.
F
l
o
u
r
o
q
u
i
n
o
l
o
n
e
s
:
L
e
v
o
f
l
o
x
a
c
i
n
:

T
a
b
l
e
t
s

L
e
v
o
f
l
o
x
a
c
i
n
:

5
0
0
-
1
0
0
0

m
g

d
a
i
l
y
.
L
o
n
g
-
t
e
r
m

(
>

s
e
v
e
r
a
l

w
e
e
k
s
)

u
s
e

o
f
L
e
v
o
f
l
o
x
a
c
i
n
:
A
v
o
i
d

i
n

p
r
e
g
n
a
n
c
y

L
e
v
o
f
l
o
x
a
c
i
n
:
S
e
p
a
r
a
t
e

a
n
t
a
c
i
d
s

a
n
d

o
t
h
e
r

L
E
V
O
F
L
O
X
A
C
I
N
,

(
2
5
0

m
g
,

5
0
0

m
g
,

7
5
0

m
g
)
,
M
o
x
i
f
l
o
x
a
c
i
n
:

4
0
0

m
g

d
a
i
l
y
.
f
l
u
o
r
o
q
u
i
n
o
l
o
n
e
s

n
o
t

a
p
p
r
o
v
e
d

f
o
r
G
a
s
t
r
o
i
n
t
e
s
t
i
n
a
l

d
i
s
t
u
r
b
a
n
c
e
:

N
a
u
s
e
a

a
n
d

b
l
o
a
t
i
n
g
(
t
e
r
a
t
o
g
e
n
i
c
)
1
6
-
2
0
%

i
n

C
S
F
m
e
d
i
c
a
t
i
o
n
s

c
o
n
t
a
i
n
i
n
g

d
i
v
a
l
e
n
t

M
O
X
I
F
L
O
X
A
C
I
N
,

a
n
d
I
V

I
n
j
e
c
t
i
o
n
:

5

m
g
/
m
L
,

c
h
i
l
d
r
e
n

a
n
d

a
d
o
l
e
s
c
e
n
t
s

b
e
c
a
u
s
e

o
f
N
e
u
r
o
l
o
g
i
c

e
f
f
e
c
t
s
:

D
i
z
z
i
n
e
s
s
,

i
n
s
o
m
n
i
a
,

c
o
m
p
a
r
e
d

t
o

s
e
r
u
m
.
c
a
t
i
o
n
s

a
t

l
e
a
s
t

2

h
o
u
r
s

a
p
a
r
t

G
A
T
I
F
L
O
X
A
C
I
N

h
a
v
e

t
h
e
M
o
x
i
f
l
o
x
a
c
i
n
:

T
a
b
l
e
t
s

(
4
0
0

m
g
)
c
o
n
c
e
r
n
s

a
b
o
u
t

e
f
f
e
c
t
s

o
n

b
o
n
e

a
n
d
t
r
e
m
u
l
o
u
s
n
e
s
s
,

h
e
a
d
a
c
h
e
f
r
o
m

f
l
u
o
r
o
q
u
i
n
o
l
o
n
e
s

(
c
a
n

m
o
s
t

a
c
t
i
v
i
t
y

a
g
a
i
n
s
t

M
.
T
B
.
C
i
p
r
o
f
l
o
x
a
c
i
n
:

T
a
b
l
e
t
s

c
a
r
t
i
l
a
g
e

g
r
o
w
t
h
.

H
o
w
e
v
e
r
,

m
o
s
t

C
u
t
a
n
e
o
u
s

r
e
a
c
t
i
o
n
s
:

R
a
s
h
,

p
r
u
r
i
t
i
s
,
m
a
r
k
e
d
l
y

d
e
c
r
e
a
s
e

a
b
s
o
r
p
t
i
o
n
)
.

L
E
V
O
F
L
O
X
A
C
I
N

i
s

t
h
e
(
2
5
0

m
g
,

5
0
0

m
g
,

7
5
0

m
g
)
e
x
p
e
r
t
s

a
g
r
e
e

t
h
e

d
r
u
g

s
h
o
u
l
d

b
e

p
h
o
t
o
s
e
n
s
i
t
i
v
i
t
y

p
r
e
f
e
r
r
e
d

o
r
a
l

d
r
u
g

c
o
n
s
i
d
e
r
e
d

f
o
r

c
h
i
l
d
r
e
n

w
i
t
h

M
D
R

T
B
.

w
h
e
n

f
i
r
s
t
-
l
i
n
e

d
r
u
g
s
O
p
t
i
m
a
l

d
o
s
e

n
o
t

k
n
o
w
n
.

c
a
n
n
o
t

b
e

u
s
e
d
.

L
o
n
g
-
t
e
r
m

s
a
f
e
t
y

a
n
d

t
o
l
e
r
a
b
i
l
i
t
y

d
a
t
a

l
i
m
i
t
e
d

f
o
r

M
O
X
I
F
L
O
X
A
C
I
N

e
s
p
e
c
i
a
l
l
y

a
t

d
o
s
e
s

a
b
o
v
e

4
0
0

m
g
/
d
a
y
.

C
r
o
s
s
-
r
e
s
i
s
t
a
n
c
e

a
m
o
n
g

C
I
P
R
O
F
L
O
X
A
C
I
N
,

O
F
L
O
X
A
C
I
N
,

a
n
d

L
E
V
O
F
L
O
X
A
C
I
N
.
R
e
f
e
r
e
n
c
e
s
:

1
.

A
m
e
r
i
c
a
n

T
h
o
r
a
c
i
c

S
o
c
i
e
t
y
,

e
t

a
l
.

"
T
r
e
a
t
m
e
n
t

o
f

T
u
b
e
r
c
u
l
o
s
i
s
.
"

A
m
e
r
i
c
a
n

J
o
u
r
n
a
l

o
f

R
e
s
p
i
r
a
t
o
r
y

a
n
d

C
r
i
t
a
l

C
a
r
e

M
e
d
i
c
i
n
e

1
6
7

(
2
0
0
3
)
:

6
0
3
-
6
6
2
.
7
6
T
a
b
l
e

3
T
B

M
e
d
i
c
a
t
i
o
n

D
o
s
i
n
g

A
d
j
u
s
t
m
e
n
t
s

f
o
r

A
d
u
l
t

P
a
t
i
e
n
t
s

w
i
t
h

R
e
d
u
c
e
d

R
e
n
a
l

F
u
n
c
t
i
o
n

a
n
d

A
d
u
l
t

P
a
t
i
e
n
t
s

R
e
c
e
i
v
i
n
g

D
i
a
l
y
s
i
s

1
,
2
>

5
0
1
0

t
o

5
0
<

1
0
H
e
m
o
d
i
a
l
y
s
i
s
P
D
*
C
R
R
T
*
I
s
o
n
i
a
z
i
d
N
o

c
h
a
n
g
e
N
o

c
h
a
n
g
e
N
o

c
h
a
n
g
e
D
o
s
e

a
f
t
e
r

d
i
a
l
y
s
i
s
N
o

c
h
a
n
g
e
N
o

c
h
a
n
g
e
R
i
f
a
m
p
i
n
N
o

c
h
a
n
g
e
5
0
-
1
0
0
%
5
0
-
1
0
0
%
N
o

c
h
a
n
g
e
D
o
s
e

f
o
r

G
F
R

<

1
0
D
o
s
e

f
o
r

G
F
R

3
0

t
o

5
0
R
i
f
a
b
u
t
i
n
N
o

c
h
a
n
g
e
N
o

c
h
a
n
g
e
N
o

c
h
a
n
g
e
N
o

c
h
a
n
g
e
N
o

c
h
a
n
g
e
1
0
0
%
P
y
r
a
z
i
n
a
m
i
d
e
N
o

c
h
a
n
g
e
N
o

c
h
a
n
g
e
5
0
-
1
0
0
%
2
5
-
3
5
m
g
/
k
g

p
e
r

d
o
s
e

3
x
/
w
k

(
n
o
t

d
a
i
l
y
)

a
f
t
e
r

d
i
a
l
y
s
i
s
N
o

c
h
a
n
g
e
D
o
s
e

f
o
r

G
F
R

1
0

t
o

5
0
E
t
h
a
m
b
u
t
o
l
1
0
0
%

q
2
4
h
1
0
0
%

q
2
4
-
3
6
h
1
0
0
%

q
4
8
h
1
5
-
2
5

m
g
/
k
g

3
x
/
w
k

(
n
o
t

d
a
i
l
y
)

a
f
t
e
r

d
i
a
l
y
s
i
s
D
o
s
e

f
o
r

G
F
R

<

1
0
1
0
0
%

q
2
4
-
3
6
h
C
y
c
l
o
s
e
r
i
n
e
1
0
0
%

q
1
2
h
1
0
0
%

q
2
4
h
1
0
0
%

q
3
6
-
4
8
h
2
5
0

m
g

o
n
c
e

d
a
i
l
y
,

o
r

5
0
0
m
g

p
e
r

d
o
s
e

3
x
/
w
k
N
o

c
h
a
n
g
e
D
o
s
e

f
o
r

G
F
R

1
0

t
o

5
0
E
t
h
i
o
n
a
m
i
d
e
N
o

c
h
a
n
g
e
N
o

c
h
a
n
g
e
5
0
%
2
5
0
-
5
0
0

m
g

p
e
r

d
o
s
e

d
a
i
l
y
N
o

c
h
a
n
g
e
N
o

c
h
a
n
g
e
S
t
r
e
p
t
o
m
y
c
i
n
1
0
0
%

q
2
4
h
1
0
0
%

q
2
4
-
7
2
h
1
0
0
%

q
7
2
-
9
6
h
1
2
-
1
5

m
g
/
k
g

p
e
r

d
o
s
e

2
x
-
3
x
/
w
k

(
n
o
t

d
a
i
l
y
)

2
0
-
4
0
m
g
/
L
/
d
D
o
s
e

f
o
r

G
F
R

1
0

t
o

5
0
,

m
e
a
s
u
r
e

l
e
v
e
l
s
o
r

5
0
%

n
o
r
m
a
l

d
o
s
e

a
f
t
e
r

d
i
a
l
y
s
i
s
A
m
i
k
a
c
i
n
1
2
-
1
5

m
g
/
k
g

p
e
r

d
o
s
e

2
x
-
3
x
/
w
k

(
n
o
t

d
a
i
l
y
)

1
5
-
2
0
m
g
/
L
/
d
D
o
s
e

f
o
r

G
F
R

1
0

t
o

5
0
,

m
e
a
s
u
r
e

l
e
v
e
l
s
1
0
0
%

q
1
2
-
2
4
h
1
0
0
%

q
2
4
-
7
2
h

b
y

l
e
v
e
l
s
1
0
0
%

q
4
8
-
7
2
h

b
y

l
e
v
e
l
s
o
r

5
0
%

n
o
r
m
a
l

d
o
s
e

a
f
t
e
r

d
i
a
l
y
s
i
s
K
a
n
a
m
y
c
i
n
1
2
-
1
5

m
g
/
k
g

p
e
r

d
o
s
e

2
x
-
3
x
/
w
k

(
n
o
t

d
a
i
l
y
)

1
5
-
2
0
m
g
/
L
/
d
D
o
s
e

f
o
r

G
F
R

1
0

t
o

5
0
,

m
e
a
s
u
r
e

l
e
v
e
l
s
1
0
0
%

q
1
2
-
2
4
h
1
0
0
%

q
2
4
-
7
2
h

b
y

l
e
v
e
l
s
1
0
0
%

q
4
8
-
7
2
h

b
y

l
e
v
e
l
s
o
r

5
0
%

n
o
r
m
a
l

d
o
s
e

a
f
t
e
r

d
i
a
l
y
s
i
s
C
a
p
r
e
o
m
y
c
i
n
1
0
0
%

q
2
4
h
1
0
0
%

q
2
4
h
1
0
0
%

q
4
8
h
1
2
-
1
5

m
g
/
k
g

p
e
r

d
o
s
e

2
x
-
3
x
/
w
k

(
n
o
t

d
a
i
l
y
)

N
o

c
h
a
n
g
e
5
m
g
/
k
g

q
2
4
h

(
o
r

g
i
v
e

d
o
s
e

a
f
t
e
r

d
i
a
l
y
s
i
s

o
n
l
y
)
P
A
S
N
o

c
h
a
n
g
e
5
0
-
7
5
%
5
0
%
4

g
r
a
m

p
e
r

d
o
s
e

t
w
i
c
e

d
a
i
l
y

a
f
t
e
r

d
i
a
l
y
s
i
s
D
o
s
e

f
o
r

G
F
R

<

1
0
D
o
s
e

f
o
r

G
F
R

1
0

t
o

5
0
L
e
v
o
f
l
o
x
a
c
i
n
N
o

c
h
a
n
g
e
2
5
0
-
7
5
0

m
g

q
2
4
-
4
8
h

2
5
0
-
5
0
0

m
g

q
4
8
h

7
5
0
-
1
,
0
0
0

m
g

p
e
r

d
o
s
e

3
x
/
w
k

(
n
o
t

d
a
i
l
y
)
,

o
r

D
o
s
e

f
o
r

G
F
R

<

1
0
D
o
s
e

f
o
r

G
F
R

<

1
0
5
0
0

m
g

q
4
8
h

(
5
0
0
-
7
5
0

m
g

i
n
i
t
i
a
l

d
o
s
e
)

(
5
0
0

m
g

i
n
i
t
i
a
l

d
o
s
e
)
C
i
p
r
o
f
l
o
x
a
c
i
n
N
o

c
h
a
n
g
e
5
0
-
7
5
%
5
0
%
2
5
0

m
g

q
1
2
h

(
2
0
0
m
g

i
f

I
V
)
2
5
0

m
g

q
8
h

(
2
0
0
m
g

i
f

I
V
)
4
0
0

m
g

q
2
4
h
*

A
b
b
r
e
v
a
t
i
o
n
s
:

P
D

=

p
e
r
i
t
o
n
e
a
l

d
i
a
l
y
s
i
s

C
R
R
T

=

C
o
n
t
i
n
u
o
u
s

r
e
n
a
l

r
e
p
l
a
c
e
m
e
n
t

t
h
e
r
a
p
y
R
e
f
e
r
e
n
c
e
s
:

1
.

A
m
e
r
i
c
a
n

T
h
o
r
a
c
i
c

S
o
c
i
e
t
y
,

e
t

a
l
.

"
T
r
e
a
t
m
e
n
t

o
f

T
u
b
e
r
c
u
l
o
s
i
s
.
"

A
m
e
r
i
c
a
n

J
o
u
r
n
a
l

o
f

R
e
s
p
i
r
a
t
o
r
y

a
n
d

C
r
i
t
a
l

C
a
r
e

M
e
d
i
c
i
n
e

1
6
7

(
2
0
0
3
)
:

6
0
3
-
6
6
2
.

2
.

A
r
n
o
n
o
f
f
,

G
.
,

e
t

a
l
.

D
r
u
g

P
r
e
s
c
r
i
b
i
n
g

i
n

R
e
n
a
l

F
a
i
l
u
r
e
.

D
o
s
i
n
g

G
u
i
d
e
l
i
n
e
s

f
o
r

A
d
u
l
t
s
.

5
t
h

e
d
.

P
h
i
l
a
d
e
l
p
h
i
a
:

A
m
e
r
i
c
a
n

C
o
l
l
e
g
e

o
f

P
h
y
s
i
c
i
a
n
s
,

2
0
0
7
.

5
2
,

5
3
,

6
7
,

7
1
,

7
2
,

7
3
.
G
F
R
,

m
L
/
m
i
n

A
d
j
u
s
t
m
e
n
t

f
o
r

R
e
n
a
l

F
a
i
l
u
r
e

(
%

d
o
s
e

o
f

n
o
r
m
a
l

r
e
n
a
l

f
u
n
c
t
i
o
n

f
o
l
l
o
w
e
d

b
y

i
n
t
e
r
v
a
l
)

D
i
a
l
y
s
i
s

D
o
s
i
n
g
77
TB Drug Interacting Drug Effect
Parenteral Cephalosporins
Nephrotoxicity may be increased. Bactericidal activity against certain pathogens may be enhanced.
Monitor aminoglycoside levels and kidney function closely.
Certain parenteral Penicllins
(Ampicillin, Penicillin G,
Piperacillin, Ticarcillin)
Certain parenteral penicillins may inactivate certain aminoglycosides. Do not mix parenteral
aminoglycosides and penicillins in the same solution.
Loop Diuretics (Bumetanide,
Ethacrynic Acid, Furosemide)
Auditory toxicity may be increased. Hearing loss of varying degrees may occur. Irreversible hearing
loss has occurred.
Polypeptide Antibiotics
(Bacitracin, Colistimethate)
May increase the risk of respiratory paralysis and renal dysfunction.
Vancomycin May increase risk of nephrotoxicity. Monitor renal function and serum drug concentration.
Digoxin Reduced serum concentration of digoxin. The actions of digoxin may be reduced.
Ethionamide May result in excessive adverse effects (GI distress and hepatotoxicity).
Vitamin B12 (Cyanocobalamin)
Biologic and therapeutic action of Vitamin B12 may be reduced. Patients requiring more than one
month of aminosalicylic acid may require supplemental Vitamin B12. In patients requiring both drugs
concurrently, administer the Vitamin B12 parenterally.
Antacids or mineral supplements
or products containing calcium,
iron, magnesium, or zinc
Aborption of antibiotics may be reduced. Administer 2 hours before or 6 hours after these products.
Antidiabetic agents
Changes in blood glucose and increased of risk of hypoglycemia or hyperglycemia. Monitor blood
glucose.
Caffeine Pharmacologic effects of caffeine may be increased. Excessive caffeine intake should be avoided.
Clozapine Clozapine levels may be elevated, increasing risk of adverse effects.
Corticosteroid May increase risk of tendon rupture.
Cyclosporine May increase cyclosporine toxicity.
Methadone Methadone levels may be elevated, increasing pharmacologic and adverse effects.
Methotrexate May increase methotrexate concentration, increasing risk of toxicity.
Phenytoin May decrease phenytoin concentration, decreasing the therapeutic effects.
Ropinirole May increase systemic toxicity of ropinirole
Sevelamer May decrease absorption of ciprofloxacin. Space administration times by at least 4 hours.
Sucralfate Decrease ciprofloxacin effectiveness. Space 2 hours before or 6 hours after sucralfate.
Theophylline
Increased theophylline levels with toxicity can occur. Monitor theophylline levels and observe for
toxicity. Adjust theophylline dosage as needed.
Tizanidine
Tizanidine concentrations may be elevated, increasing pharmacologic and adverse reactions.
Coadminstration is contraindicated.
Warfarin May increase anticoagulant effect of warfarin. Monitor INR.
Clofazimine Antacids
Concurrent administration of clofazimine with aluminum-magnesium-containing antacids should be
avoided due to the decreased absorption .
Alcohol / Ethanol May result in an increased risk of seizures. Concurrent use is contraindicated.
Ethionamide May result in neurologic adverse effects, including seizures.
Isoniazid
May result in an increased incidence of cycloserine central nervous system side effects, most
notably dizziness.
Aluminum salts
Aluminum salts delay and reduce the absorption of ethambutol. Separate administration by several
hours.
Ethionamide
May result in excessive adverse effect (GI distress, headache, confusion, neuritis, and
hepatotoxicity). Diabetic patients are more likely to experience heptotoxicity and have more difficulty
with diabetic management.
Aminosalicylic Acid May result in excessive adverse effects (GI distress and hepatotoxicity).
Cycloserine May result in neurologic adverse effects, including seizures.
Ethambutol
May result in excessive adverse effect (GI distress, headache, confusion, neuritis, and
hepatotoxicity). Diabetic patients are more likely to experience heptotoxicity and have more difficulty
with diabetic management.
Isoniazid May result in peripheral neuritis, hepatotoxicity and encephalopathy.
Pyrazinamide
May increase hepatotoxicity. Diabetic patients are more likely to experience heptotoxicity and have
more difficulty with diabetic management.
Rifampin May increase hepatotoxicity
Acetaminophen May increase hepatotoxicity
Alcohol / Ethanol
May increase hepatotoxicity. Concurrent use may result in decreased isoniazid concentrations and
disulfiram-like reactions.
Aluminum salts
Decrease concentration of Isoniazid. Administer Isoniazid 1-2 hours before Aluminum-containing
compounds.
Carbamazepine
May increase carbazmazepine concentration resulting in toxicity, Increase hepatotoxic metabolites of
Isoniazid.
Chlorzoxazone
Plasma concentrations of chlorzoxazone may be elevated, increasing the therapeutic and adverse
effects.
Cycloserine
The combination may result in an increased incidence of cycloserine central nervous system side
effects, most notably dizziness.
Disulfiram
Coadministration may result in acute behavioral and coordination changes. Acute encephalopathy
has occurred with disulfiram alone.
Ethionamide May result in peripheral neuritis, hepatotoxicity and encephalopathy.
Itraconazole May result in loss of itraconazole efficacy.
TB Medication Drug Interactions
Ethionamide
Cycloserine
Aminosalicylic Acid
Ciprofloxacin
Ethambutol
Isoniazid
Aminoglycosides
(Amikacin,
Capreomycin,
Kanamycin,
Streptomycin)
Table 4: Major Drug Interactions of TB Medications
1,2,3

(continued over)
78
Ketoconazole The therapeutic effect of ketoconazole maybe attenuated.
Levodopa May result in symptomatic deterioration of Parkinson's disease
Meperidine Hypotensive episode or CNS depression may occur wen these agents are given together.
Metformin Isoniazid may cause hyperglycemia and this may lead to loss of glycemic control.
Phenytoin
Phenytoin serum concentration may be increased, producing an increase in pharmacologic and toxic
effects of phenytoin.
Theophylline
Mild reductions and elevations in theophylline plasma levels have occurred with this drug
combination.
Valproic acid, Divalproex sodium
The toxic effects of both drugs may be increased. Elevated valproic acid levels were reported in one
patient.
Warfarin
The anitcoagulant activity of coumarin anticoagulants may be enhanced when isoniazid is
adminstered. Monitor INR
or products containing calcium,
iron, magnesium, or zinc
Antiarrhythmic Agents
The risk of life-threatening cardiac arrhythmias, including torsades de pointes, may be increased.
Avoid in patients receiving Class IA (eg. Quinidine, procainamide) or Class III (eg. Amiodarone,
sotalol) antiarrhythmic agents.
Antidiabetic agents
glucose.
Erythromycin
May increase risk of life-threatening cardiac arrhythmias, including torsades de pointes.
Levofloxacin should be avoided, moxifloxacin should be used with caution.
Methadone May increase risk of life-threatening cardiac arrhythmias, including torsades de pointes.
NSAID (non-steroidal anti-
inflammtory drugs)
May increase risk of CNS stimulation and convulsive seizures, especially in patients who are
predisposed to seizure activities.
Phenothiazines (Chlorpromazine,
Fluphenazine, Prochlorperazine,
Promethazine)
Sucralfate Decrease levofloxacin effectiveness. Space 2 hours before or 2 hours after sucralfate.
Sunitinib May increase risk of QT interval prolongation. Use with caution.
Theophylline
Adverse reactions, including seizures, may occur with or without an elevation in serum theophylline.
Theophylline dosage made if appropriate.
Tricyclic Antidepressants
(Amitriptyline, Clomipramine,
Desipramine, Doxepin,
Imipramine, Nortriptyline,
Trimipramine)
Ziprasidone
May increase risk of life-threatening cardiac arrhythmias, including torsades de pointes. Ziprasidone
is contraindicated with drugs that have demonstrated QT prolongation (eg. Levofloxacin).
or products containing iron,
magnesium, or zinc
Antiarrhythmic Agents
The risk of life-threatening cardiac arrhythmias, including torsades de pointes, may be increased.
Avoid in patients receiving Class IA (eg. Quinidine, procainamide) or Class III (eg. Amiodarone,
sotalol) antiarrhythmic agents.
Antidiabetic agents
glucose.
Erythromycin
May increase risk of life-threatening cardiac arrhythmias, including torsades de pointes. Moxifloxacin
should be used with caution.
Methadone May increase risk of life-threatening cardiac arrhythmias, including torsades de pointes.
Phenothiazines (Chlorpromazine,
Fluphenazine, Prochlorperazine,
Promethazine)
Sucralfate Aborption of antibiotics may be reduced. Administer 4 hours before or 8 hours after these products.
Sunitinib May increase risk of QT interval prolongation. Use with caution.
Tricyclic Antidepressants
(Amitriptyline, Clomipramine,
Desipramine, Doxepin,
Imipramine, Nortriptyline,
Trimipramine)
Ziprasidone
May increase risk of life-threatening cardiac arrhythmias, including torsades de pointes. Ziprasidone
is contraindicated with drugs that have demonstrated QT prolongation (eg. Moxifloxacin).
Levofloxacin
Isoniazid
(con't)
Moxifloxacin
1,2,3
(continued)
(continued over)
79
Cyclosporine
Whole blood cyclosporine concentrations may be decreased, possible resulting in a decrease in the
immunosuppressive action of cyclosporine.
Ethionamide
Increase hepatotoxicity. Diabetic patients are more likely to experience heptotoxicity and have more
difficulty with diabetic management.
Probenecid May result in increased serum uric acid levels and worsening of gout symptoms.
Zidovudine
Decrease efficacy of pyrazinamide. Monitor pyrazinamide serum levels in patients receiving
concurrent zidovudine therapy.
Pyridoxine Levodopa
Reduced effectiveness of levodopa in Parkinson's disease. No interaction if patient is taking
levodopa/carbidopa (eg. Sinemet) combinations.
Amiodarone May reduce concentrations of amiodarone, reducing its pharmacologic effect.
Amprenavir
Rifampin may reduce amprenavir plasma levels, decreasing the pharmacologic effect. Amprenavir
may increase rifabutin levels, increasing the risk of adverse reactions. Concurrent use is
contraindicated.
Aprepitant Concurrent use may result in decreased plasma concentrations and efficacy of aprepitant.
Atovaquone
Concurrent use may result in reduction of atovaquone plasma concentrations and could result in
subtherapeutic plasma concentration in some patients. The concomitant administration of
atovaquone and rifampin is not recommended.
Azole Antifungal Agents
(Fluconazole, Itraconazole,
Ketoconazole)
Plasma levels of azole antifungal agents may be decreased. Ketoconazole may decrease rifamycin
levels and itraconazole may increase rifabutin levels. Monitor antimicrobial activity.
Barbiturates May increase rate of barbiturates metabolism, reducing its pharmacologic effect.
Benzodiazepines (Alprazolam,
Clonazepam, Diazepam,
Midazolam, Triazolam)
The pharmacologic effects of certain benzodiazepines may be decreased. Monitor the clinical
response to the benzodiazepine. Adjust the dose as needed.
Beta-Blockers (Bisoprolol,
Metoprolol, Propranolol)
** Atenolol and Nadolol less to
likely to interact as they are not
metablized by the liver.
Pharmacologic effects of certain beta-blockers may be reduced. May need a 3-4 week wash out
period for the enzyme induction effect to disappear. Monitor therapeutic response and adjust dose if
necessary.
Bosentan
A transient increase in bosentan trough concentration followed by a decrease in the concentration at
steady state. Closely monitor patients receiving bosentan when starting or stopping a rifamycin.
Adjust the dose of bosentan as needed.
Buspirone
Buspirone plasma concentrations and pharmacologic effects may be decreased. Monitor clinical
response.
Carbamazepine
May elevate carbamazepine levels and toxicity. Monitor patient for signs of carbamazepine toxicity.
A carbamazepine plasma concentration may be helpful in diagnosing the toxicity.
Caspofungin Caspofungin plasma concentrations may be reduced, decreasing the therapeutic effect.
Clopidogrel
The antiplatelet effect of clopidogrel may be enhanced. Monitor platelet function when starting,
stopping or changing the rifamycin dose.
Clozapine
Decrease clozapine concentration, decreasing the therapeutic effect. Monitor clozapine
concentration and observe the clinical response.
Corticosteroids: Systemic
(Betamethasone, Cortisone,
Dexamethasone,
Fludrocortisone, Hydrocortisone,
Methylprednisolone,
Prednisolone, Prednisone,
Triamcinolone)
The pharmacologic effects of corticosteroids may be decreased. Loss of disease control has been
reported. This may occur within a few days of adding rifampin and reverse 2 to 3 weeks following its
discontinuation. Avoid this combination if possible. Otherwise, monitor the patient closely and be
prepared to at least double the corticosteroid dosage following addition of rifampin 300 mg/d.
Cyclosporine
Immunosuppressive effects of cyclosporine may be reduced. This appears to occur as early as 2
days following the initiation of rifamycins and may persist for 1 to 3 weeks after discontinuation.
Increased doses of cyclosporine may be necessary. Frequent monitoring of cyclosporine
concentrations and serum creatinine is required during rifamycin therapy and following its
discontinuation. Avoid this combination if possible.
Dapsone Pharmacologic effect of dapsone may be decreased.
Delavirdine Decrease delavirdine plasma concentrations. Avoid concurrent use.
Digoxin
May decrease digoxin concentration and reducing the therapeutic effect. Monitor digoxin level and
adjust dose as needed.
Diltiazem May reduce diltiazem effectiveness. Monitor the patient and adjust the dose as needed.
Doxycycline
May decrease concentration and half-life of doxycycline, possible reducing the therapeutic effect.
Monitor the clinical response.
Entacapone
Concurrent use of ENTACAPONE and RIFAMPIN may result in an increased risk of enhanced
entacapone adverse effects (diarrhea, dyskinesias). Monitor the patient for signs of excessive
entacapone adverse effects.
Erlotinib
Erlotinib plasma concentration may be reduced, decreasing the therapeutic effects. Consider
alternative, otherwise consider increasing the dose of erlotinib.
Estrogens
May impair the effectiveness of estrogens; menstrual disturbances have been noted. Consider
alternate methods of contraception or raising the estrogen dose.
Fentanyl
Fentanyl plasma concentrations may be reduced, decreasing efficacy. Monitor patient response
when a rifamycin is started or discontinued. Adjust fentanyl dosage as needed.
Gefitinib
Gefitinib plasma concentrations may be reduced, decreasing efficacy. Monitor response and adjust
gefitinib dose as needed.
Haloperidol
Haloperidol plasma concentrations may be reduced, decreasing efficacy. Monitor response and
adjust haloperidol dose as needed.
Pyrazinamide
Rifamycins
Rifamycins
(con't)
1,2,3
(continued)
(continued over)
80
HMG-CoA Reductase Inhibitors
(Atorvastatin, Fluvastatin,
Simvastatin)
HMG-CoA Reductase inhibitor levels may be reduced, decreasing the pharmacologic effects.
Pravastatin is not significantly metabolized by the CYP system. Rosuvastatin has no clinically
significant cytochrome P450 interactions.
Imatinib
Imatinib plasma concentrations may be reduced, decreasing efficacy. Monitor response. Consider
alternative agents for rifamycin therapy.
Indinavir For all Antiretroviral Drugs: consult with TB Control regarding coadministration with Rifampin or Rifabutin
Lamotrigine
Lamotrigine plasma concentrations may be reduced, decreasing efficacy. Monitor response and
adjust lamotrigine dose as needed.
Lapatinib
Lapatinib plasma concentrations may be reduced, decreasing efficacy. Avoid concurrent use.
Otherwise, gradually titrate the dose of lapatinib from 1250 to 4500 mg/day based on tolerability. If
rifamycin is discontinued, reduce lapatinib to the indicated dose.
Leflunomide
Concurrent use may result in an increased risk of elevated leflunomide metabolite levels. Closely
monitored for signs of leflunomide toxicity, including hepatotoxicity.
Losartan
Losartan plasma concentrations may be reduced, decreasing antihypertensive effects. Monitor
response and adjust therapy as needed.
Macrolide & Related Antibiotics
(Clarithromycin, Erythromycin)
Decreased antimicrobial effects of macrolides. Increased frequency of GI and Rifamycin adverse
reactions. Monitor patient.
Meglitinides (Nateglinide,
Repaglinide)
Meglitinide plasma concentrations may be reduced, decreasing efficacy. Monitor blood glucose and
adjust meglitinide dose as needed.
Methadone
Actions of methadone may be reduced. Patients receiving chronic methadone treatment may
experience withdrawal symptoms. A higher dose of methadone may be required during concurrent
use.
Morphine
The analgesic effects of morphine may be decreased. Observe the patient's clinical response to
morphine. It may be necessary to administer an alternative analgesic.
Mycophenolate Mofetil
Mycophenolate plasma concentrations may be reduced, decreasing efficacy. Monitor
mycophenolate concentration and adjust mycophenolate dose as needed when rifamycin therapy is
started or stopped.
Nelfinavir For all Antiretroviral Drugs: consult with TB Control regarding coadministration with Rifampin or Rifabutin
Nifedipine
The therapeutic effects of nifedipine may be reduced. Monitor BP and for angina symptoms. Adjust
nifedipine dose as needed or consider an alternative antihypertensive medication.
NNRT Inhibitors (Efavirenz,
Nevirapine)
For all Antiretroviral Drugs: consult with TB Control regarding coadministration with Rifampin or Rifabutin
Oral Contraceptives
Reduced oral contraceptive efficacy and increased incidence of menstrual abnormalities may occur.
Advise patients to use an additional form of non-hormonal contraception while receiving rifampin
therapy.
Phenytoin
Phenytoin levels may be decreased, resulting in a possible decrease in pharmacologic effects.
Monitor phenytoin levels and observe for a decrease in phenytoin activity or an increase in toxicity if
rifampin is added to or discontinued from the treatment regimen. Adjust dose of phenytoin as
needed.
Praziquantel
Praziquantel plasma levels may be greatly reduced, possibly producing a loss in therapeutic effect.
Avoid praziquantel in patients receiving rifamycins
Progestins
Increase elimination rate of progestin containing oral contraceptive steroids. Advise patients to use
an additional form of non-hormonal contraception while receiving rifampin therapy.
Propafenone
Increased propafenone clearance producing a decrease in plasma levels and a possible loss of
therapeutic effects. Avoid concurrent use if possible. Otherwise, monitor propafenone levels and
observe for loss of therapeutic effect. Adjust propafenone dose as needed.
Quetiapine
Concurrent use may result in decreased serum quetiapine concentrations. Monitor patient.
Increased doses of quetiapine may be required.
Quinine Derivatives (Quinidine,
Quinine)
Reduced therapeutic effects of quinine derivatives. Monitor and adjust dose as needed.
Ritonavir For all Antiretroviral Drugs: consult with TB Control regarding coadministration with Rifampin or Rifabutin
Saquinavir For all Antiretroviral Drugs: consult with TB Control regarding coadministration with Rifampin or Rifabutin
Serotonin Reuptake Inhibitors
(Citalopram, Sertraline)
The therapeutic effect of certain SRIs may be decreased, resulting in withdrawal-type symptoms.
Monitor clinical response to certain SRIs when starting, stopping or changing the dose of rifamycin.
Sulfonylureas (Chlorpropamide,
Glimepiride, Gliclazide,
Glyburide, Tolbutamide)
May decrease the serum levels and increasing the clearance of some sulfonylureas, possible
resulting in hyperglycemia. Monitor blood glucose.
Tacrolimus
The immunosuppressive effects of tacrolimus may be reduced as early as 2 days after starting
rifamycins. Closely monitor tacrolimus whole blood concentrations when a rifamycin is started or
stopped. Adjust tacrolimus dose as needed.
Tadalafil Concurrent use may result in decreased tadalafil plasma concentrations.
Tamoxifen
Plasma concentrations of tamoxifen may be reduced, decreasing the antiestrogenic effect. Monitor
the clinical response and adjust the dose of tamoxifen as needed.
Theophylline
May decrease theophylline levels and exacerbation of pulmonary symptoms. Monitor theophylline
levels and adjust dose as needed.
Thiazolidinediones (Pioglitazone,
Rosiglitazone)
May reduce thiazolidinediones plasma concentrations and increase clearance, possiblly resulting in
decreased glycemic control. Closely monitor blood glucose and glycosylated hemoglobin when
starting or stopping rifamycin therapy.
Thyroid Hormones (levothyroxine)
TSH levels may be increased, resulting in hypothyroidism. Monitor thyroid status and adjust
levothyroxine dose as needed.
Rifamycins
(con't)
1,2,3
(continued)
(continued over)
81
Trimethoprim, Trimethoprim-
sulfamethoxazole (TMP-SMZ)
TMP-SMZ serum levels may be reduced, decreasing the therapeutic effect. Monitor for a decrease
in the therapeutic effect.
Verapamil May reduce verapamil effectiveness. Monitor the patient and adjust the dose as needed.
Voriconazole
Voriconazole plasma concentrations may be reduced, decreasing the therapeutic effect. Rifabutin
plasma levels may be elevated, increasing the risk of adverse reactions. Coadministration with
rifampin or rifabutin is contraindicated.
Warfarin
Decrease the anticoagulation action of warfarin. Monitor INR when rifamycins are started or
stopped. Adjust warfarin dose as needed. Monitoring of INR may be needed for several weeks after
discontinuing the rifamycin.
Zopiclone
The pharmacologic effects of zopiclone may be decreased by rifampin. Monitor the clinical response
and adjust zopiclone dose as needed.
References 1.
2. Micromedex Healthcare Series. 2009. Thomson MICROMEDEX. <http://www.thomsonhc.com/hcs/librarian>.
3.
4.
Date Modified: June 30, 2010
Tatro, David (ed). Drug Interaction Facts 2009. Missouri: Wolters Kluwer Health, 2009.
Repchinsky, Carol et al. (eds). CPS 2010 Compendium of Pharmaceuticals and Specialties: The Canadian Drug Reference for Health Professionals. Ottawa: Canadian
Pharmacists Association, 2010.
"Lexi-Comp ONLINE." 2010. Lexi-Comp. <http://online.lexi.com/crlsql/servlet/crlonline>.
Rifamycins
(con't)
1,2,3
(continued)
82
TABLE 5: RIFAMYCIN (RIFAMPIN, RIFABUTIN, AND RIFAPENTINE) DRUG INTERACTIONS 1
INTERACTING DRUG EFFECTS MANAGEMENT
ACE INHIBITORS
ENALAPRIL
The pharmacologic effects of ENALAPRIL
may be decreased, resulting in a decrease
in antihypertensive control when
administered with RIFAMPIN.
Consider monitoring blood pressure in
patients receiving this combination.
If hypertension occurs, alternative
antihypertensive treatment may be
necessary.
AMIODARONE Serum concentrations of AMIODARONE and
its active metabolite may be decreased,
reducing its pharmacologic effect.
Closely monitor AMIODARONE serum
concentrations when starting or stopping
a RIFAMYCIN.
AMPRENAVIR RIFAMPIN may reduce AMPRENAVIR plasma
levels, decreasing the pharmacologic
effect. AMPRENAVIR may increase
RIFABUTIN plasma levels, increasing the
risk of adverse effects.
Coadministration of AMPRENAVIR and
RIFAMPIN is contraindicated.
Carefully monitor the patients response
to AMPRENAVIR and observe the patient
for side effects during administration
of RIFABUTIN and RIFAPENTINE. Be
prepared to alter the dose of these
agents as needed. Consider decreasing
the dose of RIFABUTIN at least 50% when
administered with AMPRENAVIR.
ANTICOAGULANTS

DICUMAROL
WARFARIN
RIFAMPIN decreases the anticoagulation
action of WARFARIN.
Increased dosage of ANTICOAGULANTS
may be needed when RIFAMYCINS are
coadministered. Monitor ANTICOAGULANT
parameters frequently when starting
or stopping RIFAMYCINS. Be prepared
to adjust the ANTICOAGULANT dose.
Monitoring and adjusting the
ANTICOAGULANT dose may be necessary
for several weeks after discontinuing the
RIFAMYCIN.
AZOLE ANTIFUNGAL
AGENTS
FLUCONAZOLE
ITRACONAZOLE
KETOCONAZOLE
Plasma levels of AZOLE ANTIFUNGAL AGENTS
may be decreased; KETOCONAZOLE may
decrease RIFAMYCIN levels; ITRACONAZLE
may increase RIFABUTIN levels.
If concurrent use cannot be avoided,
monitor antimicrobial activity, and
adjust the dosages as needed.
83
BARBITURATES

Coadministration of RIFAMPIN and
BARBITURATES may result in an increased
rate of BARBITURATES metabolism and
resultant reduced actions.
When RIFAMPIN is added to the regimen
of a patient receiving a BARBITURATE,
monitor the patient for changes in
clinical status and plasma BARBITURATE
levels. The BARBITURATE dosage may need
to be raised.
BENZODIAZEPINES
(OXIDATIVE)
ALPRAZOLAM
CLONAZEPAM
DIAZEPAM
MIDAZOLAM
TRIAZOLAM
The pharmacologic effects of certain
BENZODIAZEPINES may be decreased.
Monitor the clinical response to the
BENZODIAZEPINE when starting or stopping
RIFAMYCIN. Adjust the dose as needed.
BETA-BLOCKERS
BISOPROLOL
METOPROLOL
PROPRANOLOL
ATENOLOL
NADOLOL
The pharmacologic effects of certain
BETA-BLOCKERS may be reduced by
RIFAMYCINS. May need a 3- to 4-week
washout period for the enzyme induction
effect to disappear.
Atenolol and Nadolol are less likely to
interact as they are not metabolized by
the liver.
Close monitoring of therapeutic response
(e.g. blood pressure) is essential. If the
clinical condition deteriorates, a higher
dose of BETA-BLOCKERS may be necessary.
BUSPIRONE BUSPIRONE plasma concentrations and
pharmacologic effects may be decreased.
In patients receiving BUSPIRONE, closely
observe the clinical response when
starting, stopping, or changing the dose
of a RIFAMYCIN. Adjust the BUSPIRONE dose
as needed.
CHLORAMPHENICOL CHLORAMPHENICOL serum levels
progressively decrease, possibly leading
to decreased anti-infective action. These
effects could continue for days after
RIFAMPIN is withdrawn.
The CHLORAMPHENICOL dose may
need to be increased during RIFAMPIN
coadministration if the expected
therapeutic response is not forthcoming.
CLOFIBRATE Clearance of p-chlorophenoxyisobutyric
acid (CPIB; clofibric acid) increases
during concurrent RIFAMPIN therapy,
thereby resulting in lower steady-state
serum clofibric acid concentrations.
Observe for changes in serum lipoprotein
concentrations during concurrent
RIFAMPIN therapy. If control of serum
lipoprotein concentrations is lost,
consider discontinuing RIFAMPIN
or increasing CLOFIBRATE dose during
co-administration.
84
CLOPIDOGREL The antiplatelet effect of CLOPIDOGREL
may be enhanced by RIFAMYCINS.
Carefully monitor platelet function
when starting, stopping, or changing the
RIFAMYCIN dose. Adjust the CLOPIDOGREL
dose as needed.
CLOZAPINE RIFAMYCINs may decrease CLOZAPINE
serum concentrations, decreasing the
therapeutic effect.
Monitor serum CLOZAPINE concentrations
and observe the clinical response of the
patient when RIFAMYCINS are started or
stopped. If the RIFAMYCIN is discontinued,
observe the patient for signs of CLOZAPINE
toxicity. Adjust the dose of CLOZAPINE as
needed.
CONTRACEPTIVES, ORAL Reduced ORAL CONTRACEPTIVE efficacy
and increased incidence of menstrual
abnormalities may occur.
Advise patients to use an additional form
of contraception while receiving RIFAMPIN
therapy.
CORTICOSTEROIDS
BETAMETHASONE
CORTISONE
DEXAMETHASONE
FLUDROCORTISONE
HYDROCORTISONE
METHYLPREDNISOLONE
PREDNISOLONE
PREDNISONE
TRIAMCINOLONE
The pharmacologic effects of
CORTICOSTEROIDS may be decreased. Loss
of disease control has been reported. This
may occur within a few days of adding
RIFAMPIN and reverse 2 to 3 weeks
following its discontinuation.
Avoid this combination if possible. If
combined use cannot be avoided, monitor
the patient closely and be prepared to at
least double the CORTICOSTEROID dosage
following addition of RIFAMPIN 300mg per
day.
CYCLOSPORINE The immunosuppressive effects of
CYCLOSPORINE may be reduced. This
appears to occur as early as 2 days
following the initiation of RIFAMYCINS
and may persist for 1 to 3 weeks after
discontinuation.
Increased doses of CYCLOSPORINE may
be necessary during concomitant
RIFAMYCIN therapy. Frequent monitoring
of CYCLOSPORINE concentrations and
serum creatinine is required during
RIFAMYCIN therapy and following its
discontinuation. Avoid this combination
if possible.
DELAVIRDINE RIFAMYCINS may decrease FELAVIRDINE
plasma concentrations.
Avoid concurrent use of FELAVIRDINE and
RIFAMYCINS.
DIGOXIN RIFAMPIN may reduce DIGOXIN serum
concentrations, decreasing the
therapeutic effect.
An increased DIGOXIN dosage may
be necessary. Monitor serum DIGOXIN
concentration and tailor the dose as
needed. A decreased dose may be
required upon RIFAMPIN discontinuation
to avoid toxicity.
85
DISOPYRAMIDE RIFAMPIN may decrease the serum levels
of DISOPYRAMIDE. However, since the levels
of an active metabolite may increase,
it is difficult to predict if a decreased
therapeutic response would occur.
Monitor DISOPYRAMIDE
concentrations and the patients
electrocardiogram during concurrent
RIFAMPIN therapy. An increased
DISOPYRAMIDE dose may be necessary.
DOXYCYCLINE RIFAMYCINS may decrease the serum
concentration and half-life of
DOXYCYCLINE, possibly reducing the
therapeutic effect.
Monitor the clinical response of the
patient. It may be necessary to increase
the dose of DOXYCYCLINE. (Streptomycin
dose not appear to decrease DOXYCYCLINE
concentrations.)
ERLOTINIB ERLOTINIB plasma concentrations may
be reduced, decreasing the therapeutic
effects.
In patients receiving ERLOTINIB, consider
alternative therapy with a drug that does
not induce metabolism. If alternative
therapy is not available, consider
increasing the dose of ERLOTINIB.
ESTROGENS

RIFAMYCINS may impair the effectiveness
of ESTROGENS; menstrual disturbances
have been noted.
Consider alternate methods of
contraception or raising the ESTROGEN
dose.
HALOPERIDOL RIFAMYCINS may decrease the plasma
concentration and clinical effectiveness of
HALOPERIDOL.
When adding or discontinuing
RIFAMYCIN therapy in a patient receiving
HALOPERIDOL, carefully monitor the
clinical response of the patient. Adjust
the HALOPERIDOL dose as indicated.
HMG-COA REDUCTASE
INHIBITORS
ATORVASTATIN
FLUVASTATIN
SIMVASTATIN
HMG-COA REDUCTASE INHIBITOR levels may
be reduced, decreasing the pharmacologic
effects. PRAVASTATIN levels may be
increased in some patients.
patient; if an interaction is suspected,
it may be necessary to administer
alternative therapy or increase the dose
of the HMG-COA REDUCTASE INHIBITOR when
a RIFAMYCIN is coadministered.
PHENYTOIN Serum PHENYTOIN levels may be
decreased, resulting in a possible
decrease in pharmacologic effects of
HYDANTOINS.
Monitor serum HYDANTOIN levels and
observe the patient for a decrease in
HYDANTOIN activity or an increase
in toxicity if RIFAMPIN is added to or
discontinued from the treatment regimen.
Tailor the HYDANTOIN dosage as needed.
86
IMATINIB IMATINIB plasma concentrations may
effect.
In patients receiving IMATINIB, closely
monitor the clinical response when
RIFAMYCIN therapy is started or stopped.
Consider alternative agents for RIFAMYCIN
therapy.
INDINAVIR RIFAMYCINS may decrease INDINAVIR serum
concentrations. In addition, INDINAVIR
may elevate serum RIFABUTIN and
RIFAMPIN concentrations, increasing the
risk of toxicity.
For all antiretroviral drugs consult with
TB Control regarding co-administration
with RIFAMPIN or RIFABUTIN.
LAMOTRIGINE LAMOTRIGINE plasma levels may be
reduced, decreasing the pharmacologic
effects.
It may be necessary to adjust the
dose of LAMOTRIGINE when starting,
stopping, or changing the dose of the
RIFAMYCIN. Observe the clinical response
of the patient and adjust the dose of
LAMOTRIGINE as needed.
LINEZOLID LINEZOLID serum concentrations may be
reduced, decreasing the pharmacologic
effects.
In patients receiving LINEZOLID, monitor
the clinical response when starting or
stopping RIFAMPIN. Be prepared to adjust
therapy as needed.
LOSARTAN LOSARTAN plasma concentrations may be
reduced, decreasing the antihypertensive
effects.
Observe the clinical response of the
patient when RIFAMYCIN is started or
stopped. Adjust therapy as needed.
MACROLIDE & RELATED
ANTIBIOTICS

CLARITHROMYCIN

ERYTHROMYCIN

Decreased antimicrobial effects of
MACROLIDE & RELATED ANTIBIOTICS.
Increased frequency of adverse GI
reactions and adverse effects of
RIFAMYCINS.
If these agents are used concurrently,
monitor for increased RIFAMYCIN
side effects and a decrease in the
response to the MACROLIDE & RELATED
ANTIBIOTIC. Avoid coadministration
of TELITHROMYCIN and a RIFAMYCIN.
Azithromycin and dirithromycin do not
undergo metabolism and may be safer
alternatives.
MEGLITINIDES

NATEGLINIDE

REPAGLINIDE
MEGLITINIDE plasma concentrations and
pharmacologic effects may be decreased.
In patients receiving a MEGLITINIDE,
closely monitor blood glucose levels when
starting or stopping RIFAMYCIN therapy.
Adjust the MEGLITINIDE dose as needed.
METHADONE
The actions of METHADONE may be
reduced. Patients receiving chronic
METHADONE treatment may experience
withdrawal symptoms.
A higher dose of METHADONE may be
required during coadministration of
RIFAMPIN.
87
MORPHINE The analgesic effects of MORPHINE may be
decreased.
Observe the patients clinical response to
MORPHINE analgesia. It may be necessary
to administer an alternative analgesic.
NELFINAVIR RIFAMYCINS may decrease NELFINAVIR
serum concentrations, decreasing the
pharmacologic effects.
NIFEDIPINE The therapeutic effects of NIFEDIPINE may
be reduced.
Monitor blood pressure and for angina
symptoms. Adjust the NIFEDIPINE dose
accordingly or consider an alternative
antihypertensive medication.
NNRT INHIBITORS
EFAVIRENZ
NEVIRAPINE
NON-NUCLEOSIDE REVERSE TRANSCRIPTASE
(NNRT) INHIBITOR plasma concentrations
may be reduced, decreasing the efficacy.
Based on available data, no special
precautions are needed other than
routine monitoring. Be aware of the
possible interaction and if an interaction
is suspected, it may be necessary to adjust
the dose of the NNRT INHIBITOR.
PRAZIQUANTEL PRAZIQUANTEL plasma levels may be
greatly reduced, possibly producing a loss
in therapeutic effect.
Avoid administration of PRAZIQUANTEL to
patients receiving RIFAMYCINS.
PROGESTINS RIFAMPIN may increase the elimination
rate of PROGESTINcontaining oral
contraceptive steroids.
Patients who require concurrent
contraception and antitubercular
therapy should avoid either use of oral
contraceptives or RIFAMPIN.
PROPAFENONE Increased PROPAFENONE clearance
producing a decrease in plasma levels
and a possible loss of therapeutic effects.
Consider an alternative anti-infective
agent for patients stabilized on
PROPAFENONE. If coadministration can
not be avoided, monitor PROPAFENONE
serum levels and observe the patient
for loss of therapeutic effect. Adjust the
PROPAFENONE dose accordingly.
QUININE DERIVATIVES Reduced therapeutic effects of QUININE
DERIVATIVES may occur.
Addition of RIFAMYCINS to stable regimens
of QUININE DERIVATIVES may require
increased doses of QUININE DERIVATIVES to
maintain the desired therapeutic effect.
Withdrawal of RIFAMYCINS may result in
QUININE DERIVATIVESdose-related toxicity.
Monitor QUININE DERIVATIVES serum levels
and the ECG.
QUETIAPINE Concurrent use may result in decreased
serum QUETIAPINE concentrations.
Monitor patient. Increased doses of
QUETIAPINE may be required.
88
RITONAVIR RIFAMYCINS may decrease RITONAVIR serum
levels. RITONAVIR may elevate serum
RIFABUTIN levels, increasing the risk of
RIFABUTIN hematologic toxicity.
SAQUINAVIR RIFAMYCINS may decrease SAQUINAVIR
serum concentrations. In addition,
SAQUINAVIR may elevate serum RIFAMYCIN
concentrations, increasing the risk of side
effects.
SEROTONIN REUPTAKE
INHIBITORS
CITALOPRAM
SERTRALINE
The therapeutic effect of certain
SEROTONIN REUPTAKE INHIBITORS (SRIS) may
be decreased, resulting in withdrawal-
type symptoms (e.g. dizziness, lethargy).
Carefully monitor clinical response to
certain SRIs when starting, stopping, or
changing the dose of the RIFAMYCIN.
SULFONES
DAPSONE
The pharmacologic effect of DAPSONE
may be decreased.
Monitor for clinical failure of DAPSONE
when administered with a RIFAMYCIN.
Higher doses of DAPSONE may be
necessary. Consider alternative
Pneumocystis carinii pneumonia
prophylaxis when a RIFAMYCIN is used.
SULFONYLUREAS
CHLORPROPAMIDE
GLICLAZIDE
GLIMEPIRIDE
GLYBURIDE
TOLBUTAMIDE
RIFAMYCINS may decrease the half-life
and serum levels while increasing
the clearance of some SULFONYLUREAS,
possibly resulting in hyperglycemia.
Closely monitor blood glucose. The dose
of the SULFONYLUREA may need to be
increased.
TACROLIMUS The immunosuppressive effects of
TACROLIMUS may be reduced as early as
2 days after starting RIFAMYCINS.
Closely monitor TACROLIMUS whole blood
concentrations when a RIFAMYCIN is
started or stopped. Adjust the dose of
TACROLIMUS as indicated.
TADALAFIL Concurrent use may result in decreased
TADALAFIL concentrations.
Assess clients for decreased TADALAFIL
effectiveness.
TAMOXIFEN Plasma concentrations of TAMOXIFEN may
be reduced, decreasing the antiestrogenic
effect.
Monitor the clinical response of
the patient. It may be necessary to
increase the dose of TAMOXIFEN during
coadministration of a RIFAMYCIN.
THEOPHYLLINES

The addition of a RIFAMYCIN may cause
decreased THEOPHYLLINE levels and
exacerbation of pulmonary symptoms.
In patients receiving THEOPHYLLINE,
monitor THEOPHYLLINE levels and the
patients response when starting or
stopping a RIFAMYCIN. Adjust the dose as
needed.
89
THIAZOLIDINEDIONES
PIOGLITAZONE
ROSIGLITAZONE
RIFAMYCINS may reduce plasma
concentrations and t while increasing
the clearance of THIAZOLIDINEDIONES,
possibly resulting in decreased glycemic
control.
In patients receiving THIAZOLIDINEDIONES,
closely monitor blood glucose and
glycosylated hemoglobin when starting or
stopping RIFAMYCIN therapy.
THYROID HORMONES
LEVOTHYROXINE
Thyroid-stimulating hormone (TSH)
levels may be increased, resulting in
hypothyroidism.
Monitor thyroid status in patients
receiving LEVOTHYROXINE when RIFAMYCIN
therapy is started or stopped. Adjust the
dose of LEVOTHYROXINE as needed.
TOCAINIDE The pharmacologic effects of TOCAINIDE
may be decreased.
Based on current information, no specific
recommendations can be made. Monitor
plasma TOCAINIDE levels and adjust the
dose accordingly.
TOREMIFENE Plasma concentrations of TOREMIFENEmay
be reduced, decreasing the antiestrogenic
effect.
Monitor the clinical response of
the patient. It may be necessary to
increase the dose of TOREMIFENE during
coadministration of a RIFAMYCIN.
TRIMETHOPRIM
TRIMETHOPRIM
TRIMETHOPRIM-
SULFAMETHOXAZOLE
TRIMETHOPRIM-SULFAMETHOXAZOLE
(TMP-SMZ) serum levels may be reduced,
decreasing the therapeutic effect.
In patients receiving TMP-SMZ, monitor
for a decrease in therapeutic effect during
coadministration of RIFAMPIN.
VERAPAMIL Loss of clinical effectiveness of oral
VERAPAMIL.
Use IV VERAPAMIL or substitute another
agent for VERAPAMIL or RIFAMPIN. If
RIFAMPIN is stopped, lower the dose of
VERAPAMILand monitor closely.
VORICONAZOLE VORICONAZOLE plasma concentrations may
effect. RIFABUTIN plasma levels may
be elevated, increasing the risk of side
effects.
Coadministration of VORICONAZOLE and
RIFAMPIN or RIFABUTIN is contraindicated.
WARFARIN Decrease the anticoagulation action of
WARFARIN.
Monitor INR when RIFAMYCINS are
started or stopped. Adjust WARFARIN
dose as needed. Monitoring of INR
may be needed for several weeks after
discontinuing the RIFAMYCIN.
ZIDOVUDINE The pharmacologic effects of ZIDOVUDINE
may be decreased.
If an interaction is suspected, consider
increasing the dose of ZIDOVUDINE.
ZOLPIDEM Plasma concentrations and therapeutic
effects of ZOLPIDEM may be reduced.
patient. The dose of ZOLPIDEM may
need to be increased during concurrent
administration of RIFAMYCINS.
Reference: 1. David S. Tatro. Drug Interaction Facts 2007. St. Louis, Missouri: 2007.
90
APPENDIX D: PEDIATRIC TB/ISSUES IN PREGNANCY & POSTPARTUM
The majority of TB cases in children in Canada are diagnosed in Aboriginal
persons and the foreign-born. Case numbers remain very low. The diagnosis of TB
in a child should be considered a "sentinel event", or a sign of recent transmission
of infection. Similarly, contact screening for adult cases of TB should focus on
identifying all pediatric contacts.
There are three stages of TB in children: exposure, infection and disease.
1. TB EXPOSURE AND EVALUATION FOR PRIMARY PROPHYLAXIS
(PREVENTATIVE THERAPY):

All children under 5 years of age (and/or immune-compromised) with a history
of contact* with an active case of TB require symptom inquiry, physical xamination,
baseline TST and PA chest radiograph. The dose of tuberculin is the same for adults
as children. Screening includes all children under 5 years of age who have had
contact with an active pulmonary TB case, regardless of smear status, and with a
focus on close or household contacts

A positive TST at baseline is managed as per section 2 once active TB is ruled out.

Children under 5 years of age that are exposed to an active, infectious case of TB
and are TST negative (asymptomatic, normal examination and chest radiograph,
and active TB excluded) should be considered for primary preventative therapy
with Isoniazid until a repeat TST can be performed in 8 weeks post-date of last
contact.

If the follow-up TST at 8 weeks is negative, Isoniazid can be stopped unless the
child is immune-compromised or symptomatic. Children 6 months of age or
under may not be able to mount a TST response; therefore, isoniazid may be
continued until a repeat TST at 6 months. Guidance should be sought from TB
Control in individual cases.

If the follow-up TST is positive (equal to or greater than 5 mm), a repeat chest
radiograph and clinical evaluation are suggested to rule out evidence of active TB. If
active TB is ruled out, Isoniazid is continued to complete 9 months. Rifampin is an
option if the child was exposed to an isoniazid resistant case.

2. TREATMENT OF LATENT TB INFECTION OR LTBI (SECONDARY PROPHYLAXIS):

A positive TST (equal to or greater than 10mm, or equal to or greater than 5 mm
in contacts) requires follow-up with clinical evaluation and chest radiograph to
rule out active TB. If both are normal, Isoniazid treatment of LTBI is strongly
suggested for 9 months.

91

A positive TST in a child should raise the question of potential sources of infection.
Children with positive tuberculin reactions should NOT be excluded from school.

Isoniazid treatment is dosed 10 mg/kg per day to a maximum of 300 mg daily and
is also available in syrup form.
Vitamin B6 is not recommended for children 16 years of age or under in the
absence of malnourishment or solely breast-fed infants.

Routine blood work is not required in children 16 years of age or under in the
absence of known liver disease or clinical concern.
3. ACTIVE TB DISEASE
The diagnosis of active TB in a child indicates recent TB transmission within a
community and should alert health care professionals to initiate appropriate
nvestigations for a potential source case. This includes "reverse contact tracing",
or the identification of any sick adults the child may have been in contact with.
The diagnosis of TB in children is often based upon a history of TB contact with an
adult case of TB, positive tuberculin skin test, abnormal chest radiograph, and
less commonly, non-specific symptoms and bacteriology.
A negative TST does NOT rule out active TB.
Young children may not be able to produce adequate sputum specimens.
Early morning gastric aspirates on 3 separate days, sputum induction, and
ronchoscopy are alternative means of obtaining respiratory specimens if
clinically indicated.
Radiographic manifestations of primary TB in childhood can include hilar and/
or paratracheal lymphadenopathy with a small pulmonary focus. PA and lateral
views should be submitted for review.
With rare exceptions (e.g. cavitary or laryngeal disease), children with TB are
not considered contagious due to a low bacillary burden of disease. Routine
respiratory isolation is not required.
TB disease is an early complication of LTBI. Children under 5 years of age are at
increased risk of progressing from infection to disease, and are at increased risk
for developing severe forms of TB such as disseminated, miliary and meningeal
TB. Treatment of active disease should be initiated promptly upon suspicion of
TB.
Children are dosed with anti-TB medications by weight (mg/kg) and in general,
these medications are extremely well tolerated.
92
Regimens recommended in children are similar to those used in the adult
population but there are some important exceptions. Ethambutol carries a low
risk of optic neuritis in children and may be used in consultation with a TB
expert however visual monitoring remains an issue in younger children. The use
of respiratory Quinolones (i.e. Levofloxacin and Moxifloxacin) in the growth-
phase is also not recommended. Streptomycin should be avoided due to potential
auditory and vestibular toxicity.
Vitamin B6 and routine blood work is not required in the pediatric population (<16
years) in the absence of clinical concern or symptoms.
The indications for adjunctive Corticosteroid use in children are the same
as in adults.
Follow-up during treatment is by clinical assessment and chest radiography.
PREGNANCY AND BREASTFEEDING
Treatment of LTBI in pregnancy is usually postponed until after delivery unless
recent contact or infection with HIV.

TB skin tests are safe in pregnancy.

If symptomatic, chest radiographs must be performed with appropriate shielding.

Treatment of active TB in pregnancy should NOT be withheld because there is a
greater risk of TB to the fetus compared with anti-TB treatment

Therapy for 9 months with Isoniazid and Rifabutin should be adequate if
Ethambutol is substituted for Pyrazinamide in the first two months and the
organism is fully sensitive.

Although the teratogenic risk of Pyrazinamide has not been determined, the use of
Pyrazinamide should be considered if drug resistant TB is suspected

Streptomycin has been associated with congenital deafness; its use is not
recommended
Breastfeeding should NOT be discouraged for women being treated for TB or LTBI.
Concentrations of these drugs in breast milk are too small to produce toxicity
in the nursing newborn. Breastfeeding women taking Isoniazid should also take
Pyridoxine (Vitamin B6) supplementation.

93
NEWBORN TB
Tuberculin skin testing can be performed in newborns. Skin test reactivity may be
difficult to interpret in children 6 months of age.
Children born to mothers with LTBI require no special investigation or treatment.
Children born to mothers with abnormal chest radiographs or symptoms
compatible with active TB should be separated until the diagnosis is clarified.

If the diagnosis of TB is confirmed in the mother or another contact at delivery,
the child should be separated from the source case until the source is deemed
non-infectious. The placenta should be sent for histopathology and culture. The
child should be evaluated for congenital TB, and if present, treated promptly.
If congenital TB is excluded, Isoniazid should be given for 6 months with TST
repeated at 3 and 6 months. Isoniazid can be stopped if the newborn has a
negative TST at 3 and 6 months. If the TST is positive, re-evaluation for active
TB is recommended. If active TB is excluded and the TST is positive, continue
Isoniazid for 9 months.
Children born to mothers with abnormal chest radiographs compatible with old TB
(but no evidence of active TB and asymptomatic) should be skin tested at 3 and 6
months. These mothers should be encouraged to take treatment for LTBI. If there
is any uncertainty as to the status of TB in the mother, the child should be placed
on preventative therapy.

Screening in children should be targeted to testing children at risk including:
Contacts of a known case; this should include all contacts under 5
94
APPENDIX E: TUBERCULOSIS SERVICES FOR ABORIGINAL COMMUNITIES
Tuberculosis Services for Aboriginal Communities* (TBSAC) is a section of Tuberculosis
Control, a division of the British Columbia Centre for Disease Control. One of the
mandates of this program is to provide consultative services to Physicians and Nurses
providing health care to First Nations individuals living on reserve
. TBSAC provides
this service in partnership with Health Canada, First Nations & Inuit Health.
This portion of the Communicable Disease Control TB Manual presents standards, policies
and procedures that are unique to First Nations communities in British Columbia. All
other standards, policies and procedures for the control of tuberculosis in British Columbia
are presented in earlier sections of this manual.
Historically, high rates of latent TB infection and active TB disease in First Nations
communities have created an environment at increased risk for the development and
transmission of TB. Despite active case management and screening programs, which
have contributed to an overall decline in rates of TB in First Nations communities, TB
remains an ongoing public health concern. The incidence of TB disease in First Nations
communities is far greater than that of Canadian-born/non-Aboriginal persons.
The primary objective of the TBSAC program is the ultimate reduction and
elimination of TB in First Nation communities. For all active cases of TB, directly
observed therapy (DOT) is recommended for the duration of treatment.
PREVENTIVE PROGRAMS INCLUDE:
Community risk stratification
Enhanced surveillance of children 5 years of age or under
Screening of individuals, groups and communities at increased risk
of developing active TB disease
School screening & employment screening
Consideration of DOPT for individuals taking Isoniazid treatment of
LTBI
TB education and in-service resources for communities and health
care staff
The goal of these measures is to contribute to the prevention of TB transmission
and to decrease morbidity, family disruption, and the social stigma of TB in First
Nations communities.
Tuberculosis Services for Aboriginal Communities (TBSAC) 888-569-2299
TBSAC Director/Physician Consultant 604-707-2729
TBSAC Nurse Consultant 604-707-2695
TBSAC Nurse Consultant 604-707-2732
TBSAC Clinical Nurse Educator 250-878-4928
* The term Aboriginal is a collective name used to describe the indigenous peoples of North America and their descendants. Aboriginal
peoples in Canada include Status and non-Status Indians (commonly known as First Nations), Inuit (of Arctic Canada) and Mtis
(mixed First Nations and European Heritage) as reported by Health Canada, First Nations and Inuit Health.
A reserve has been defned as a tract of land set apart for use and beneft by First Nations.
95
TBSAC PROGRAM
The following recommendations for surveillance activities in First Nations
communities are dependant on the level of risk for the individual, group or
community of developing active TB disease.
1.0 ANNUAL SCREENING RECOMMENDED FOR ALL COMMUNITIES (TABLE E-1, PAGE 101)
A. EMPLOYEES
Employees of Health Centres, Band Schools, Day Care Centres, Treatment Centres,
Alcohol & Drug programs, and Pre-Schools should be screened upon employment.
Employees with a negative tuberculin skin test (TST) should receive a two-step TST
at baseline (i.e. repeat TST within 2-4 weeks following the initial TST). This should
be followed by annual TST screening and symptom enquiry. For management of
employees with a positive TST, see Appendix E-5 (page 102) "Isoniazid Treatment
of latent tuberculosis infection (LTBI)".
Persons with a previous positive TST should be sent for a baseline chest x-ray.
Thereafter, follow-up should include documentation of annual symptom enquiry
and repeat chest x-ray, only if symptoms suggestive of TB occur or if they have
been in contact with an active case of TB disease.

The responsibility to enforce this employment requirement is at the discretion of
the Band or Health Centre Administration.
B. SCHOOL TB SCREENING
It is recommended that the tuberculin skin test (TST) be ofered to school children
entering Grade 1 and Grade 6 attending a Band School. Written or verbal
informed consent by a parent or guardian is a pre-requisite for a TST.
For previous skin test positive children, TB school screening includes symptom enquiry
(routine chest x-ray not required).
NOTE: For new positive TSTs see 'Follow Up of Children with Positive TST (p. 95).

C. INCREASED RISK GROUPS
Individuals at increased risk for developing active TB disease should be screened
annually. This includes, but is not limited to persons with the following:
HIV/AIDS
Immune deficiencies due to disease processes or medications
Renal failure
Lymphoma/Leukemia
Organ transplants
Cancer (especially head and neck)
Silicosis
X-ray findings consistent with previous untreated TB
Tuberculin skin test converted to positive within the past two years
5 years of age or under when infected
96
Diabetes
Below ideal body weight
Substance abuse/smoking
TNF- inhibitors
Symptom enquiry should be carried out and documented for persons with
increased risk and a previous positive TST on an annual basis. All clients with
symptoms of active TB disease should be referred for a chest x-ray and have three
(3) sputa samples submitted to the Mycobacteriology Laboratory for AFB smear
and culture.
2.0 RECOMMENDATIONS FOR SCREENING COMMUNITIES WITH ONE (1) OR MORE
CASES OF INFECTIOUS TB DISEASE IN THE PAST FIVE (5) YEARS (SEE TABLE E-2)

Communities that have had a recent infectious TB case are at increased risk for
further TB activity. Therefore, these communities are recommended for enhanced
surveillance, which includes A) Community Tuberculin Surveys and B) Annual
surveillance of children 5 years of age or under.
A. COMMUNITY TUBERCULIN SURVEYS
The goal of community surveys is to identify and ofer Isoniazid treatment
to individuals who have recently become infected with latent TB. High rates
of tuberculosis infection in First Nations communities still warrant periodic
comprehensive screening. Therefore, community-wide TB screening should be
conducted every two years in communities that have had one or more infectious
cases in the past fve years. The community-wide screening is broad but should
target populations at increased risk, children 5 years of age and under and all
grades in Band School.
Hosting a community survey can be enhanced by the following tips:
Host the survey during a time when maximum number of
community members are available
Promote and advertise well in advance with posters, radio,
newspapers, meetings, word of mouth, etc.
Include incentives such as draw prizes for returned consents for TST
screening in children
Drop in luncheons or other activities can increase turn out during
the survey
B. SURVEILLANCE OF CHILDREN 5 YEARS OF AGE OR UNDER
Children under 5 years of age with latent Tuberculosis infection (LTBI) are at
increased risk (up to 40%) of developing active TB disease, including the severe
forms of TB such as Miliary TB and TB Meningitis. Diagnosis of TB in children
can be dif cult because they are less likely to have obvious symptoms of TB. For
this reason, prompt diagnosis and immediate treatment of both TB infection and
TB disease are essential in pediatric cases. Treatment of LTBI in this age group is
extremely safe and efective in reducing the risk of severe disease.
97
RECOMMENDATIONS:
Annual TST should be promoted and provided to all children born after June 1,
2003 who live in communities that have had one or more cases of infectious
TB disease in the past five years. Screenings should occur at 10 months, 2, 3, 4,
and 5 years of age.
Treatment with isoniazid for all children diagnosed with latent Tuberculosis
infection by the TBSAC Physician in consultation with local health care
providers. (See page 102)

3.0 TBSAC SCREENING FOLLOW-UP
FOLLOW UP OF CHILDREN WITH POSITIVE TST
Children with a positive TST (10 mm or over) should be sent for a chest x-ray using
the Tuberculosis Screening Program Form HLTH 939.
If there has been an active case of TB disease in the community, a TST 5 mm or
over would be considered positive and a chest x-ray recommended. TB Control
will follow up with recommendations and send the reports to the Health Centre.
It is necessary to screen all close household contacts of TST positive children in
order to identify the possible source of infection (also known as reverse contact
tracing).
FOLLOW UP OF ADULTS WITH POSITIVE TST
All individuals with a positive TST (10mm or over) should have a Tuberculosis
Screening Program FormHLTH 939 completed and sent for a chest x-ray.
Symptomatic individuals with a TST 5 mm or over, who are immunocompromised
or contacts of an active case should be sent for a chest x-ray.
TST results and chest x-rays will be reviewed by TB Control and a report forwarded
to the Health Centre that initiated the form, and the family physician.
Three sputa specimens should be collected and sent to the provincial
Mycobacteriology Laboratory on all individuals who report a cough or sputum
production.
TRAVEL ASSISTANCE TO X-RAY FACILITY CHEST RADIOGRAPHS (CXR)
Clients should be supported and provided travel assistance as needed to the
nearest x-ray facility. The following clients include:
New converters (previous TST was negative and the current TST
is positive)
Converted TST within past two years, which was not followed with
an x-ray.
Clients with signs or symptoms suggestive of active TB disease
regardless of TST status. Chest x-ray and three sputa samples
are recommended.
Clients considering isoniazid treatment for latent Tuberculosis
infection (LTBI). An x-ray is required within the past six months
before starting Isoniazid.
Clients with newly diagnosed HIV should have a TST and a baseline
chest x-ray.
98
4.0 OTHER
REPORTING TO TUBERCULOSIS SERVICES FOR ABORIGINAL COMMUNITIES
(TBSAC)
Community Health Nurses should ensure that the following are sent to TBSAC:
Results of all TSTs using the Aboriginal TB Program Tuberculin
Monthly Report (HLTH 8771), or;
Tuberculosis Screening Program Form (HLTH 939)
COMMUNITY PROFILES
Profles for each First Nations community, which includes names, birth dates and
all previous TST results are available to the CHN upon request to TBSAC.
CONTACT INVESTIGATION
All newly diagnosed active TB cases require contact investigation to 1) identify any
secondary cases of TB disease and initiate treatment as soon as possible; 2) identify
newly infected individuals and ofer preventative treatment and/or appropriate
follow-up; and 3) identify the source case (when the index case is not the source
case). Section III of the TB Manual (2010) describes Contact Investigation in more
detail. Additionally, a Contact Investigation Tool specifcally for First Nations
communities is provided (FIGURE E-1).
DIRECTLY OBSERVED THERAPY (DOT)
The TBSAC program strongly supports and recommends the use of DOT for
cases of active tuberculosis disease. Recommendations from the World Health
Organization and the Canadian Tuberculosis Standards recommend DOT. DOT
should also be considered for LTBI clients taking Isoniazid treatment.
By defnition, DOT involves the direct observation of clients swallowing each
dose of their prescribed anti-tuberculous medication by a trained health care
provider. This ensures client adherence to the medication regime, and provides an
opportunity to monitor for side efects and build rapport over the long treatment
course. Research shows that poor compliance in persons with active disease may
lead to drug resistant tuberculosis.
Efective DOT requires that Community Health Representatives (CHR) or DOT
Lay Workers are trained and supervised by the Community Health Nurse (CHN).
Information for those health care workers providing DOT should include the
following:
Effective charting and communication process
Good communication skills with client
Effective medication dispensing systems, ie. Blister packs
Medications should be recorded by the CHN, CHR or DOT Lay Worker
on the Record of Supervised TB Medication Form (HLTH 832)
Duplicates of the HLTH 832 Form serve as a record of treatment and
99
the medication re-order form.
At the end of each calendar month, the original copy of the HLTH
832 should be mailed to TB Control, TBSAC and a photocopy of the
HLTH 832 kept in the client chart.
The number of doses recorded as given for that month will be
replaced by Pharmacy.

A DOT manual was developed in March 2010 to facilitate education of community
members and Community Health Representatives (CHRs) to work as DOT Lay
Workers. DOT is strongly recommended by the TBSAC program for all active
cases and for high-risk clients on preventative therapy. The DOT manual supports
capacity-building of community members, as they are well-respected, integral
members of their communities and well-situated to play a key role in prevention
and elimination of TB (see Appendix Q: DOT Manual pdf).
ACTIVE TB TREATMENT STARTER UNITS
Starter kits should be available for each First Nations community such that
treatment can be initiated without delay (ideally within 24 hours) of the diagnosis
of active TB. These kits can be maintained in the medication dispensary of each
individual First Nations Health Centre, Nursing Station, or its designate agency
(i.e. Health Authority Public Health Unit currently providing CDC services on-
reserve) as per mutual agreement.
It is the responsibility of the administrators of the First Nations Health Centre
or Nursing Station to ensure that TB medications are available as per this
recommendation.
It is the responsibility of the First Nations Health Centre or Nursing Station
maintaining the medication to ensure the integrity of the starter unit as per the
College of Registered Nurses of BC Medication Inventory Management practice
standard.

ROLES OF THE TBSAC PROGRAM

The current contractual relationship between First Nations & Inuit Health,
BCCDC, Band Health Centres and Nursing Stations ensures collaboration on the
management of TB.

1. THE ROLE OF THE TBSAC PHYSICIAN CONSULTANT
Advises the Programs Medical Officer (PMO) on all matters related to the control of
tuberculosis in First Nations communities, including planned revisions to TBSAC
program policies.
Reports all cases of active tuberculosis to the PMO, Regional Medical Health
Officer (MHO) and Community Health Nurse (CHN), and recommends
appropriate management.
100
Provides telephone consultation to physicians and nurses regarding management
and treatment of active or suspected cases of TB disease and latent Tuberculosis
infection (LTBI).
Reviews case management requests from the CHN regarding home conditions,
obstacles or other issues that may impede the success of home treatment for
clients with active TB disease.
Facilitates admission to TB Ward at Vancouver General Hospital (VGH) when required.
Interprets and makes recommendations based on chest x-rays referred from First
Nations communities.
Maintains a database, including records of active and inactive cases of
tuberculosis, contacts of active TB cases, and cases of latent TB infection.
Provides an annual activity report and statistics to the PMO.
Provides consultation regarding epidemiological trends of TB in First Nations
populations to BC physicians, nurses and other health care professionals.
Provides in-service education to physicians in BC upon request.
In cooperation with the TBSAC nurse consultants; assesses, plans, implements
and evaluates effective education programs pertaining to TB Control and policy
manual.
2. THE ROLE OF THE TBSAC NURSE CONSULTANTS
Provides support and direction to the CHN regarding diagnosis, treatment and
contact tracing associated with active cases of tuberculosis.
Reviews medication records submitted by the CHN.
Facilitates patient admission to the TB Ward at VGH when necessary.
Resource nurse for information pertaining to treatment of active disease, treatment
of LTBI, screening programs and education.
Provides on site consultation services and assists the CHN with community TB skin
testing surveys.
Provides referrals to the TB Nurse Educator and/or assists with in-service education
and workshops in the community as requested.
Notification of community risk stratifications to CHN/CHR in confidential
fashion.
In consultation with the TBSAC physician consultant, reviews and revises the
TBSAC section of the Policy Manual.
Evaluates the effectiveness of the TBSAC screening programs and assists the PMO
and TBSAC physician consultant as required.
3. THE ROLE OF THE TBSAC CLINICAL NURSE EDUCATOR
Provides in-service education and workshops to community members, CHNs, CHRs,
and other health care providers upon request.
Develops and distributes culturally appropriate education materials as required.
Assists with coordination of community based TB programs and projects, and
supports the community development process.
Resource person for TBSAC and other BCCDC staff on issues of cultural competency
and the health of First Nations populations.
101
In consultation with the TBSAC physician and nurse consultants, reviews and
revises the TBSAC section of the Policy Manual.
Evaluates the effectiveness of TB education programs.
Works in collaboration with the TBSAC nurse consultants as required.
4. THE ROLE OF THE COMMUNITY HEALTH NURSE
Participates in case finding and promptly reports to the TBSAC nurse consultant
all people with symptoms suggestive of active tuberculosis.
Identifies contacts of active cases of tuberculosis disease and conducts the
appropriate screening of these individuals.
Directly supervises the treatment for all active cases of tuberculosis and persons
on Isoniazid treatment of LTBI.
Directly trains and supervises the DOT Lay Worker.
Ensures that routine blood work is completed and symptoms monitored as
recommended in the TB Manual. Reports abnormal blood work and symptoms of
drug intolerance to the TBSAC Nurse Consultants.
Submits a monthly report of individuals taking anti-tuberculous medications to
the TBSAC Nurse Consultants.
Participates in tuberculosis education with individuals with active TB disease,
and communicating the importance of adherence to the medication regime.
Including compliance with recommendations for isolation as needed.
Coordinates and participates with the CHR and other health care providers in
community-wide tuberculosis skin testing surveys every other year if determined
to be an "at risk community".
Promotes and provides annual TST for children 5 years of age and under in
communities which have had one or more cases of infectious TB disease in the
past five years.
Annually conducts TST screening in all communities:
a. Children attending Grades 1 and 6 in all Band schools.
b. Health Centre employees, schoolteachers, day care and
preschool staff.
c. Individuals at increased risk for developing active TB disease.
Provides and/or refers tuberculosis education to First Nations communities.
If nursing station is the only local provider of acute emergency care, nurse
manages acute isoniazid toxicity from overdose see Figure E-2.
5. THE ROLE OF THE DOT LAY WORKER
Works directly under the supervision of the CHN:
Familiar with DOT manual.
Assists the CHN with the supervision of treatment for cases of active tuberculosis
and individuals on Isoniazid for treatment of LTBI.
Reports promptly to the CHN any individuals who are missing doses of anti-
tuberculous medication, and any compliance issues.
Reports promptly to the CHN any individuals who show signs or symptoms of side
effects to the anti-tuberculous medication.
Assists the CHN in planning, organization and advertising of tuberculosis surveys,
102
and provides onsite support to the CHN and TBSAC Nurse Consultant during a
survey.
Participates in the tuberculosis education within the community.
For those DOT Lay Workers trained to do enhanced practices:
Assists with sputum collection, reading tuberculin skin tests, and
sending clients for chest x-ray under the direction of the CHN.

103
FIGURE: E-1:
CONTACT INVESTIGATION TOOL (TB SERVICES FOR ABORIGINAL COMMUNITIES)
The purpose of this tool is to give practical tips and hints to get you started with efective contact investigation
in First Nations Communities in British Columbia. This tool is designed to complement Section III: Contact
Investigation of the BC Centre for Disease (BCCDC) TB Control Manual (2011).
GETTING ORGANIZED:
It is important to stay calm. Take the time to prepare and get organized.
REVIEW TB DOCUMENTS:
Review Appendix E: TB Services for Aboriginal Communities and Section III: Contact Investigation of
the BCCDC TB Control manual.
Review procedures for tuberculin skin testing and reading.
DEVELOP A COMMUNICATION PLAN:
Develop a plan for communicating with TB Control (ie. daily phone call, regular email a method that
will work for you both):
Updates of assessments should be forwarded to TB Control as work is completed.
Fax is often the fastest, most secure method to forward and exchange information. Do not send
personal information via email.
TB Control Fax #: 604-707-2690
Develop a plan for communicating with your Nurse Manager, Nurse in Charge, or Transfer Advisor
Develop a system to manage work done and due:
For example: a communication book or binder containing:
> master contact list
> monthly TB form
> current update/referral form/medication order sheets
> blank forms symptom inquiry, update & referral forms, blood work requisitions, fax
cover sheets, etc
> daytimer/calendar to enter due dates of actions and orders
GATHER YOUR TEAM:
Your Health Centre team:
Bring your team together to discuss and clarify health team roles in managing the contact
investigation:
> CHRs, community health staf, health director, clerical, transportation, local physician,
nurse manager, regional team. See Team Member Roles in Contact Investigation Table to
guide your discussion with team members.
> CHRs or other community health stafs knowledge of community will be invaluable in
developing an accurate, thorough contact list, in facilitating assessment and adequate
follow up.
104
Ofer TB in-service/information sessions for staf: eg. questions and answers & discussions on
maintaining confdentiality
Ensure all staf are providing consistent information to community
Connect with local partners:
Local family physicians
> Identify the clients family doctor (GP) as part of your initial client assessment and get
the clients consent to collaborate with their GP. Call the GP to confrm their willingness
to see the client and get to know their staf (nurse, receptionist). Being sure that the GP is
willing to see the client is an important step as an incorrect GP on a referral form or
recommendation for medication can cause major delays in starting prophylaxis.
> Call the GP and give a heads-up regarding imminent referral(s) for TB assessment.
> In circumstances where no family physician can be found please contact TB Control for
TB physician billing number
Local provincial PHN
> Alert the local PHN that you are dealing with a smear positive case. They can be an ally in
helping with lab or hospital communication and education, if required.
Labs/Hospitals
> Contact your local lab/hospital so they know to expect clients for chest x-ray and blood
work. It may be helpful to direct clients to one particular lab if feasible this would
streamline follow-up by only needing to liaise with one lab.
> Consider faxing HLTH 939 chest x-ray requisitions to lab as it helps with issues of lost
requisitions.
Checklist of what you will need:
Resources:
TB Control Manual (2011) & Appendix E
DOT manual (2010)
Canadian Tuberculosis Standards (6
th
Ed. 2007)
Supplies:
Tubersol (PPD)
tuberculin syringes
TB ruler
sputum containers and requisitions
portable scale - adult, infant
TB education material (TBSAC Forms Package & Pamphlets)
anaphylaxis kit
105
Forms:
Contact Tracing Form (HLTH 836 Form) *
Tuberculosis Screening Form (HLTH 939 Form) *
symptom inquiry
sputum requisition *
blood work requisition
letter for family Doctor (template)
Pharmanet Consent Form *
Request for Preventative Therapy Form *
* FORMS ON THE WEBSITE:
Contact Tracing List, HLTH 836 Form
http://www.bccdc.ca/NR/rdonlyres/19E17681-3F8E-46F2-90DA-0FAD4C505389/0/HLTH836_RevAugust2010.pdf
HLTH 939 Form (CXR requisition)
http://authoring.bccdc.ca/NR/rdonlyres/69DDB0EB-CC6C-458C-8EEC-67C3899C6AD2/0/HLTH939_Feb2011.pdf
Request for Preventative Therapy Form:
http://www.bccdc.ca/NR/rdonlyres/9F06251A-951B-4DAF-BDA2-0D0989F66862/0/RequestforPreventativeTherapy-
Form.pdf
Sputum Requisition Form:
http://www.bccdc.ca/NR/rdonlyres/9CDC4B7D-6587-4A17-ACEE-B6344FCA3285/0/RequisitionforSpecimenCon-
tainersSputumBottles.pdf
Pharmanet Consent Form:
http://www.bccdc.ca/NR/rdonlyres/02A86A6A-D0C6-460B-9DA6-80A419AEBE1E/0/PharmanetConsent.doc
CONDUCTING A CONTACT INVESTIGATION:
1. CREATE A CONTACT TRACING LIST:
Develop list as advised by TB Control consultation with TB Control will determine the extent of contact
list. You may receive a beginning list from TB control if the client was interviewed in the TB ward at Van-
couver General Hospital or from local public health if interviewed in local hospital.
Determine contact category:
TYPE OF CONTACT AMOUNT OF TIME WITH SOURCE CASE
Type 1 contact
More than 4 hours per week. Close household contact
Type 2 contact
2 to 4 hours per week. Close non-household contacts who share the air space on
an ongoing basis (i.e. close friends)
Type 3 contact
Less than 2 hours per week. Casual contacts, such as sports team
NOTE: High-risk contacts such as immune-suppressed individuals and children under 5 years of age should be given high priority.
106
Review fles and gather TB and medical history clerical help is very important.
Individuals may self-report as contacts. Consider how they ft into the picture and if they truly require
assessment at this time or not. Your frst priority is to assess those at highest risk (contact category).
Keep track of names of those who self report as contacts (work, social) as you may need to expand your
list later on.
Utilize community staf CHR, clerk
May use paper version or electronic version to keep track of contacts and work required. Do not send
personal information over email. Fax is often fastest, most secure method to share information.
List should be forwarded to TB Control one week following notifcation of case.
Thorough and efective contact investigation may result in additional contacts added to or removed from
the list, as more information becomes available. This is expected and the result of proper investigation.
2. PRIORITIZE YOUR CONTACTS
Ensure each contact is clearly identifed as a Type 1, Type 2 or Type 3 contact.
Start follow-up on Type 1 contacts frst:
Immune suppressed and children under 5 years of age are the highest priority. This group is
at very high risk for developing disease quickly and will therefore be ofered primary prophylax-
is regardless of their TB skin test status. They should be assessed as soon as possible including:
> TB skin test ( if not previously TST positive)
> chest x-ray with 939 form faxed to TB Control
> medical assessment by family physician
> weight
> blood work (AST and CBC)
> medication allergies
This assessment for high risk contacts should be completed by one week from diagnosis
of source case. The goal is to have children under 5 years of age, and immune-suppressed on
medication by 2 weeks from the time they were identifed as a contact.
The remainder of the close contacts (Type 1 and Type 2) should be assessed and started on their
medication by one month. For those that refuse preventative therapy, follow-up recommendations will
be made by TB Control.
Type 3 or casual contact follow-up can be completed once Type 1 and Type 2 contacts are assessed. For
mass numbers of casual contacts, discuss with TB Control appropriate documentation since it may not
be required to complete a HLTH 939 for casual contacts. Instead, a HLTH 836 form, Contact Tracing List,
might be suf cient.
107
3. START CONTACT FOLLOW-UP:
TST INTERPRETATION:
The interpretation of tuberculin skin testing has been standardized by TB Control as follows:
SIZE OF INDURATION INTERPERTATION ACTION
0 to 4 mm Negative ** Repeat TST in 8 weeks
5 mm or more Positive Send for chest x-ray
NOTE: Interpretation of a TST in the context of a contact investigation considers 5 mm or more a positive TST for close contacts.
Documenting results: For the purposes of Contact Investigation, TB Control requires a Tuberculosis
Screening Form [HLTH 939 form] for all TST results of contacts. This means positive and negative TSTs
are documented on a HLTH 939 form. Please note: Exceptions may apply for Type 3 (casual) contacts.
Forward your assessment information to TB control as it
becomes available (eg. send results of TSTs as soon as they are
read, symptom inquiries as completed, or blood work results as
soon as you receive them, etc.).
INITIAL CLIENT ASSESSMENT
Each contact will require:
Demographics of the contact (community, reserve status, etc.)
Nature of contact with case (eg. Type 1, 2, or 3 contact)
Risk Factors for developing TB (medical, social)
Symptom inquiry (send 3 sputa for AFB if symptomatic)
Past history of TB (latent or active)
Past history of treatment of TB (latent or active)
Previous documented TST results; BCG vaccination
FIRST ROUND OF TB SKIN TESTING SHOULD BE COMPLETE BY:
ONE WEEK from diagnosis of source case for all contacts with high risk medical conditions and
children under 5 years of age
ONE MONTH from diagnosis of source case for all others
SECOND ROUND OF TB SKIN TESTING:
Those who tested negative on the initial round of TB testing must have a second TB skin test 8 to 12 weeks from
last exposure to TB case.
** REMEMBER
Children < 5 years old or immuno-
compromised contacts are at increased
risk for developing active disease and
may require primary prophylaxis after
active disease is ruled out, regardless of
their initial TST result
108
LATENT TB INFECTION PROPHYLAXIS OR LTBI PREVENTATIVE THERAPY
The TB Control physician may recommend positive reactors take LTBI preventative therapy. If so, the clients
family doctor and the Health Centre will be sent a consult note recommending preventative therapy. The client
should follow-up with their family doctor to discuss the recommendation. Additionally, the CHN should provide
education to the client regarding TB disease, Latent TB Infection, LTBI treatment and medication adherence. If
the client agrees to preventative therapy, the CHN needs to advise TB Control by completing a "Request for
Preventative Therapy" form (See Appendix Q of TB Manual). Medication is prescribed and dispensed by TB
Control. Directly Observed Therapy (DOT) is recommended for all clients.
All adults (>16 years old) on preventative treatment will require regular blood work (AST). The CHN should
make arrangements with the GP for ordering and monitoring blood work.
e.g. Nurse completes requisition under GPs name as ordering physician and gives to client OR lab may
have standing order OR GPs of ce could fax requisition to lab when blood work due.
Report baseline lab results to TB Control and abnormal results only as per follow-up policy (updated
April 2009).
Medication recommendations should all have been reviewed and clients started (or declined) by:
2 weeks from notifcation for high-risk clients (i.e. Children under 5 years of age, and immune-suppressed)
One month from notifcation for all others
TIME LINES
Time 0: case identifed
Time 0 + 1 week a full contact list submitted to TB Control by this time
Time 0 + 2 weeks all high-risk contacts assessed and on medication if recommended
Time 0 + 1 month: all contacts should have had their frst round of assessments completed by this
time. Medication recommendations started or refused
Time 0 + 8 to 12 weeks: initiate second round of tuberculin skin testing. Any new medication
recommendations started or refused
Time 0 + 6 months: follow-up chest x-ray for those recommended chest x-ray follow up every 6
months for 2 years
Time 0 + 9 months: frst people on prophylaxis medication should be fnishing
Time 0 + 1 year: follow-up testing on those who were recommended no treatment and 1 year
follow-up... until follow-up & medication completed
109
TEAM MEMBER ROLES IN CONTACT INVESTIGATION
Team Member Role
Health Director authorize support for resources to take care of contact investigation
submit request to FNIH for additional funding if required
liaise with Chief and Council
Community Health Nurse educate and reassure staf re: TB & related risks
develop and prioritize contact list; amend/update as necessary
case management
complete TB assessments in timely manner
initiate medication in timely manner
manage client medication and recommended follow up
supervise DOT workers
liaise with TBSAC
Community Health Representative develop contact list
assist with TB assessments gather clients, sputum
assist with giving DOT when trained
assist with reading TST when trained
Clerk/Receptionist clerical support as required (eg. complete TB forms)
pull fles as requested
Transportation Co-ordinator arrange transport of clients to assessments and appointments
Nurse Manager ensure adequate staf ng to complete contact investigation, case
management & prophylaxis
link with FNIH CDC, TB Control & provincial health authority
liaison with Chief & Council and health director
Regional TB Co-ordinator answer general TB questions
support feld staf
arrange for additional funding when activity extends beyond what
is expected with base funding
liaison between TB Control and communities
liaison with FNIH Regional Medical Health Of cer
TB Control specifc direction on TB case management
advise on contact investigation
telephone consultation
provide education
provide historical and up-to-date TB records for contact tracing
train DOT workers
Physician Liaison with local CHN
110
APPENDIX E: FIGURE E-2
ACUTE ISONIAZID TOXICITY FROM OVERDOSE
(Protocol for nursing stations which are the only local provider of acute emergency care)

Symptoms of isoniazid overdose have occurred with doses as low as 3 g (10x300mg
tablets). The mortality rate from a single acute ingestion of isoniazid can be as high as
20%.
I. SIGNS & SYMPTOMS
Apparent 30 minutes to three hours after ingestion of Isoniazid:
Nausea and vomiting, dizziness, slurred speech, blurred vision,
atropine-like effects (dilated pupils, increased visual sensitivity to
light, tachycardia, possible urinary retention).
May proceed to stupor and deep coma.
Tonic/clonic grand mal or localized seizures may occur within one to
three hours after the ingestion of Isoniazid.
Convulsions that cannot be controlled, marked hyperreflexia or
complete absence of reflexes, Babinskis sign, severe hypotension,
cyanosis and death.
Hyperpyrexia, increased pulse rate, hypotension, oliguria
progressing to anuria.
II. LABORATORY FINDINGS
Severe metabolic acidosis, albuminuria, hyperglycemia, mild hyperkalemia,
increased urinary excretion of Pyridoxine, serum isoniazid concentration
up to 93.3 g/ml, urine concentration up to 100 g/ml.
III. EMERGENCY TREATMENT
In any patient with an overdose, the first priority is the assessment and
stabilization of the patients airway, breathing, and circulation. Call for help/
poison control.
In the event of an early presentation, prior to the onset of seizures, gastric
lavage with a large-bore orogastric tube should be performed, followed by the
administration of activated charcoal (1 g/kg). NOTE: Syrup of Ipecac-induced
emesis is not recommended for Isoniazid poisoning because of the risk for early
seizure activity and the associated high risk for aspiration pneumonia.
Pyridoxine IV immediately: Give 1 g pyridoxine IV for each gram (1000 mg) of
isoniazid ingested.
If the amount of ingested Isoniazid is not known, give 5 g of Pyridoxine IV
immediately to adults and 70mg/kg should be given to a child.
111
Repeat the same dosage in two to six hours if the patient has not responded to
earlier injections. In the frst 12 hours of treatment, up to 25 g of Pyridoxine can
be given.
IV. TREATMENT OF CONVULSIONS
Diazepam (Valium) 510 mg IV which may be repeated in two to four hours
if necessary
If Valium is not available, use Sodium Phenobarbital injections slowly, IM.
ADULTS 120mg
UNDER 12 YEARS OF AGE 60mg or less
V. SUPPORTIVE MEASURES
Oxygen
IV Sodium Bicarbonate to correct metabolic acidosis
IV fluids and Mannitol
Intubation if the patient is drowsy
VI. PREVENTIVE MEASURES
Try to ascertain emotional stability (depression or suicide tendency) of patients for
whom Isoniazid is recommended.
Caution patients about keeping their supply of Isoniazid out of reach of children.
Have IV pyridoxine and 50cc syringes available for emergency treatment.
Give small (weekly) supplies of Isoniazid and check frequently if the drug is taken
regularly in persons who are emotionally unstable; or strongly consider DOT/
DOPT.
NOTE: Report overdose cases to Tuberculosis Control
112
TABLE E-1: ANNUAL SCREENING FOR ALL COMMUNITIES
Grades 1 & 6 Employees High Risk Groups
Band Schools Health Centre, Band
Schools, Daycare and Pre-
school
HIV/AIDS, prednisone, kidney
dialysis, cancer, lymphoma, leukemia,
transplantation, low body weight,
diabetes
Tuberculin
Skin Test
(TST)
All children with previous
negative TST
All employees with previous
negative TST
Two-step TST at baseline
All clients with previous negative TST
Symptom
Enquiry
Document
Results
All children with positive
TST
All employees with positive
TST
All clients in high risk group
Chest x-ray
(CXR)
Children with a new positive
TST or symptoms of TB
Positive TST: Baseline
CXR at employment and
thereafter if symptoms of TV
occur or contact with active
TB
CXR all clients with new TST positive or
symptoms of TB regardless of TST status.
Sputum for
AFB
Productive cough for more
than 2 weeks
Productive cough for more than 2 weeks
TABLE E-2: COMMUNITIES WITH ONE OR MORE CASES OF INFECTIOUS TB DISEASE
IN THE PAST FIVE YEARS
Community-wide screening every two years Children born after June 1, 2003*
Tuberculin Skin Test (TST) screening for entire
community and should include screening of all grades
in Band Schools.
Discuss treatment with Isoniazid for all clients with
positive TSTs (Latent Tuberculosis Infection).
Annual TST screening of children at 10 months, and 2,
3, 4, & 5 years of age.
TST is positive if equal to or greater 10 mm or greater
than 5mm for contacts of an active case or if immune
compromised children.
Symptom inquiry for all clients with previous
positive TST.
CXR not required if asymptomatic.
Treatment of Latent Tuberculosis Infection (LTBI) with
Isoniazid is safe and strongly recommended.
Reverse contact tracing should happen for all new
positive TSTs in children.
Reverse contact tracing should happen for all new
positive TSTs in children.
* Starting June 1, 2004
113
ISONIAZID (INH) TREATMENT OF LATENT TUBERCULOSIS INFECTION (LTBI)*
POSITIVE PPD
- Or if productive cough
- No Cough

- TBSAC ofers INH treatment
for LTBI
- CHN provides education (pamphlet
available)
- Client agrees to INH prophylaxis
and local physician
- CHN advises TBSAC of clients decision
NORMAL CXR ABNORMAL CXR
SUBMIT 3 SPUTA
MEDICATION
BLOODWORK
MONITOR
FOLLOW AS
ACTIVE
CASE OF TB
- Negatlve SNears 3
POSITIVE
SMEAR
NEGATIVE
SMEAR
- Prescribed & dispensed by
TB Control
- Standard Regime: Isoniazid** and
Vitamin B6
***
9 Nonths
- DOT twice weekly or
self-administered daily
- Baseline: AST (not required for
children <16 years of age)
- Q Nonth for rst 3 Nonths: AST
- Then Q 2 months for duration of
treatment: AST
- Monthly for side-efects to drugs:
malaise, loss of appetite, nausea
and vomiting, tingling of hands
or feet, rash, abdominal pain
NOTES
* Isoniazid Prophylaxis
** Do not use starter kit, wait for pharmacy to send Isoniazid
*** Children under 16 years of age do not require Vitamin B6
114
MANAGEMENT OF AN ACTIVE CASE OF TUBERCULOSIS
PULMONARY TB NON-PULMONARY TB
- Sputum x 3 if productive cough
- Baseline CXR
- Smear for AFB or
- Culture for MTB
- Ensure 3 sputum collected
for baseline (3 separate days
if possible)
- 3 sputums Q 2 weeks until 3
consecutive negative smears
- Q monthly until 3
consecutive negative cultures
. A 2 month sputum collection
provides test of conversion
POSITIVE SPUTUM BASELINE SCREENING
- No isolation if Pulmonary TB
is excluded
- Monthly clinical assessment
of symptoms, improvement and
side efects of medications
- Radiological follow-up as
recommended by TB Control
FOLLOW-UP
ABNORMAL X-RAY
- Recommend DOT (Directly Observed Therapy)
- Requires prescription from TB Control
- Standard Regime: Isoniazid, Rifampin, Pyrazinamide, Ethambutol, Vit B6
MEDICATION
- Baseline: CBC, Diferential, AST
- AST at 2 weeks then:-
- Q monthly for the frst 3 months if normal followed by:
- Q 2 months for duration of treatment
- Abnormal values contact TB Control
- If on Ethambutol, baseline and monthly assessment
of visual acuity & colour discrimination
- Children: bloodwork not routinely required on children <16.
BLOOD WORK
- Monthly for side efects to drugs: rash,
malaise, loss of appetite, nausea and
vomiting, tingling of hands and feet
and vision changes.
MONITOR
- Recommended on all newly
diagnosed active cases
- Consent and Pre & Post
Counseling required
HIV SEROLOGY
- Q 2 months or as
recommended by
TB Control
X-RAY FOLLOW-UP SPUTUM
COLLECTION
- SMEAR POSITIVE: Hospital
or home until 3 negative
smears and on appropriate
treatment.
- CULTURE (+) SMEAR (-):
Isolation until 2 weeks
of treatment completed
ISOLATION
- See Contact
Tracing Algorithm.
CONTACT
TRACING
- See Contact Tracing Algorithm
CONTACT TRACING
115
PEDIATRIC PRIMARY PROPHYLAXIS OF CHILDREN
PRIMARY PROPHYLAXIS
For Children < 5 years of age who are:
MEDICATION
- Close contact to active case of TB
- Contact TB Control; initiate HLTH 939
- Negative TST at baseline
- Normal chest x-ray
- Asymptomatic
- Prescribed & dispensed by TB Control
- Standard regime: Isoniazid x 2 months minimum
- Childs weight required to determine dose
BLOOD WORK
- Not required for children <16
MONITOR
- Side efects to drugs: malaise, loss of
appetite, nausea & vomiting
- Discontinue Isoniazid after
consulting with TB Control
AT 8 WEEKS
From initial TST
or
Last date of exposure
REPEAT TST
TST POSITIVE
TST NEGATIVE
& ASYMPTOMATIC
(5mm)
- Repeat CXR
- Consult with TB Control
NOTE: For children <6 months of age, refer to Pediatric Section (appendix D) and call TB Control
116
TIME FRAME FOR CONTACT TRACING
INTERVIEW THE FOLLOWING:
- CXP
- |f symptomatlc, collect 3 sputum
INDIVIDUALS WHO HAVE A RECORD
OF A PREVIOUS POSITIVE SKIN TEST:
- TST < 5mm: Pepeat ln 8 weeks
- Symptomatlc: CXP & 3 sputum
(regardless of TST results)
- TST > 5 mm: CXP
*
- Chlldren < 5 years: TST & CXP
**
- |mmunosuppressed: TST & CXP
***
(|f TST > 5mm)
INDIVIDUALS WHO ARE PREVIOUS
NEGATIVE OR OF UNKNOWN STATUS
PROVIDE TST:
ESTABLISH CONTACT LIST
WITHIN 3 DAYS
CONTACT TRACING SHOULD
BEGIN WITHIN 7 DAYS
OF SOURCE CASE REPORT
Only interview family/close friends if condentiality
consent has been received from source case.
- Source Case
- Pamlly
- Close Prlends
- |nltlal round of TSTs and CXPs should be
completed wlthln 30 DAS of the lndex case
belng reported
- Call T8 Control lf asslstance ls requlred wlth
Contact Traclng
* treatment of LTBI prophylaxis should be considered once active
disesase is excluded.
** Children under 5 years of age who are close contacts should be
considered for Isoniazid primary prophylaxis regardless of initial
TST result. Treatment may be stopped if repeat TST at 8 weeks post-
exposure is negative.
*** HIV individuals who have a negative TST and are close contacts
should be considered for preventative therapy.
117
APPENDIX F: BCG VACCINE
BCG (Bacille Calmette-Gurin) is a live attenuated vaccine derived from M. bovis.
Although in use since 1921 and used in 172 countries around the world, it is not
a highly ef cacious vaccine with an estimated protection rate of some 50%. It
does however, have high protection against more serious forms of tuberculosis
such as meningitis and miliary TB. The of cial use of BCG vaccination has been
discontinued in the province of British Columbia since 2003.
ADMINISTRATION
BCG is given intradermally at a dose of 0.025 mL for infants and 0.1 ml for older
children. This results in an indurated papule which forms within two to three
weeks, eventually resulting in an ulcer by six to eight weeks and heals in three
months, leaving a 4 to 8 mm scar at the vaccination site. When this occurs,
it lasts for the patients life time and is a useful confrmatory sign of previous
vaccination. As it is a live vaccination, any recipient who is immuno-defcient is at
risk for disseminated disease and it should clearly be avoided in this context. Local
reactions are common and indeed expected and consist of adenitis and a localized
abscess.
RECOMMENDATIONS FOR USE
As stated, BCG is no longer routinely administered in the province of British
Columbia. It had been ofered on select reserves but this also has been phased out.
Very exceptionally, the following groups may be vaccinated:
Newborn infants born to infectious mothers, although primary
chemoprophylaxis is the usual tactic.
Travellers visiting high prevalence countries. Unfortunately the
efficacy of BCG vaccination in adults is uncertain and it is usually
preferable to perform a skin test prior to departure and repeat on
return to see if conversion has taken place which would trigger the
administration of treatment of latent infection.
Individuals repeatedly exposed to persistently untreated or
inadequately treated tuberculosis, e.g. children.
Requests for BCG vaccination prior to attending schools or colleges
should be denied as there is no rational medical indication for this
practice.
BCG vaccination does not provide complete or permanent protection and the BCG
status of a patient should be ignored when considering a diagnosis of tuberculosis.
118
FIGURE 1: TYPICAL BCG VACCINATION SCAR
OTHER USES OF BCG VACCINATION
Intra-vesicular (bladder) instillation of BCG has
been used for the treatment of transitional cell
bladder cancer. For the most part, this practice is well
tolerated and the rationale is to cause an immune
reaction with the lining of the bladder to interfere
with malignant cell progression. Occasionally, the
BCG organism can spread locally and systemically
producing a miliary pattern on chest x-ray. This can
even occur in immunocompetent patients. It responds
to conventional antituberculousis therapy but M. bovis
BCG is always resistant to pyrazinamide.
119
APPENDIX G: TUMOUR NECROSIS FACTOR
TNF INHIBITORS
Tumour necrosis factor alpha (TNF ) is a key cytokine in the infammatory
response that leads to tissue damage in several diseases including rheumatoid
arthritis, Crohns disease, psoriasis, psoriatic arthritis and ankylosing spondylitis.
TNF inhibitors, used for controlling these diseases, have been proven an
extremely useful treatment. Unfortunately, the blockage of a cytokine that is also
involved in granuloma formation has been associated with a signifcant increase
in serious infections, both common and uncommon, following the administration
of TNF inhibitors. Several products are currently available in Canada, namely
etanercept (Enbrel), infiximab (Remicade) and adalimumab (Humira). They are
sometimes referred to as "biologicals".
Infiximab is the most powerful TNF inhibitor and its biological efects can persist
for up to two months. All of these medications have been associated with increased
risks of infection, with tuberculosis being the most common pathogen reported.
Several fungal diseases such as nocardia, cryptococcus and histoplasmosis have
also been reported. In the majority of patients who have received infiximab, TB
has occurred early in treatment with 72 per cent of reported cases occurring within
90 days. With the other TNF inhibitors, the complications were spread more
evenly over the treatment period. This suggests that the mechanism leading to the
development of active tuberculosis is reactivation of latent tuberculosis infection.
The presentation of tuberculosis in those treated with TNF inhibitors is
characterized by greater frequency of extrapulmonary and disseminated
tuberculosis compared to the general population of cases. Involvement of almost
every system has been reported including miliary, pleural, peritoneal, meningeal
and genito-urinary tuberculosis.
The following are important issues regarding these medications:
1. The intended recipient of TNF inhibitors must be screened for latent TB infection.
This involves medical history, physical examination, tuberculin skin test and a
chest radiograph. This can be challenging as patients may be immunosuppressed
because of their underlying disease severity or concomitant drug treatment that
the patient is taking such as steroids or methrotrexate. This gives rise to the
possibility of false negative PPD skin tests. If the chest x-ray confirms old TB
(granulomatous disease), preventative therapy should be offered irrespective of
the skin test reaction.
2. Isoniazid is the drug of choice and there is evidence to support the fact that its use
significantly reduces the incidence of active TB disease in populations treated.

120
3. Ideally the patient should be started on treatment for latent infection prior to the
initiation of the TNF inhibitors. How long the patient should be on treatment is
controversial. We currently recommend two months of Isoniazid prior to starting
the other drugs.

4. All TNF inhibitors should be discontinued should a serious infection ensue.
5. Use of Isoniazid in older people who are frequently on concurrent hepatotoxic
drugs, mandates careful monitoring of the liver function tests.
6. Rifampin for four months is an alternative treatment regimen for LTBI but is more
likely to be associated with drug interactions.
121
APPENDIX H: ATYPICAL MYCOBACTERIA
Mycobacteria other than tuberculosis (MOTT) are important as they are the
most common mycobacteria isolated by the laboratory. Many of the species
are commonly found in the environment. A large and growing number of
species have been documented to cause human disease but isolation of atypical
mycobacteria does not always constitute proof of disease caused by the organism.
The most common organism isolated in British Columbia is Mycobacterium avium-
intracellulare (MAC). Other organisms are M. kansasii, M. absessus, M. xenopi and
M. marinum. They also are known as 'atypical mycobacteria' or 'non-tuberculousis
mycobacteria'.
The following are important considerations regarding atypical mycobacteria:

1. The clinical picture associated with atypical disease can closely mimic tuberculosis
by presenting as persistent cough, fever, hemoptysis and weight loss and have
similar x-ray fndings of predominantly upper lobe lung disease, cavitation and
nodules. Patients may have pre-existing underlying lung disease such as COPD or
bronchiectasis.

2. Atypical organisms are acid fast and are largely indistinguishable from M.
tuberculosis on smear. The probe for M. tuberculosis complex rRNA will be negative
when applied to atypical organisms (a specific probe is available for MAC from
culture).

3. Culture of an atypical organism from respiratory tract is not proof of disease
attributable to the organism as they can simply colonize the airway.

4. These organisms are not transmissible person to person and there is no need for
isolation or contact tracing, irrespective of the extent of the disease.

5. There is cross-reactivity between atypical and typical mycoacterial antigens and
therefore the skin test can be falsely positive.

6. There is a very distinct syndrome occurring in elderly women where atypical
mycobacteria are associated with bronchiectasis and nodular disease on x-ray.
This occurs predominantly in females who are non-smokers and tends to affect
different ethnic groups compared to M. tuberculosis.

7. While pulmonary disease is the most common manifestation, these organisms can
also cause lymphadenopathy or disease in any organ in those who are immuno-
compromised.

8. The histology of the granulomas formed by these organisms is indistinguishable
from M. tuberculosis.
122
9. Treatment is indicated usually when repeated sputum samples, particularly those
that are smear positive, grow on culture and when the radiological studies show
the classic fndings of cavitation, nodules and parenchymal disease. Sometimes
the decision to treat is dif cult and is usually made on the advice of a specialist.

10. Pulmonary disease can also manifest as an isolated pulmonary nodule which
are frequently resected fearing cancer. Isolated nodules do not usually require
treatment.
TREATMENT CONSIDERATIONS
Treatment of atypical mycobacteria is not as successful as M. tuberculosis despite
the relatively low virulence and in any given case the response is somewhat
unpredictable. It usually requires approximately 12 months of medication. There
is an overlap between the drugs used for typical M. tuberculosis and atypical
mycobacteria and the overlap drugs are supplied by TB Control, commonly rifampin
and ethambutol. All other antibiotics, particularly clarithromycin, azithromycin or
ciprofoxacin are not covered by the TB Control Division and are dispensed by the
local pharmacy. This frequently leads to issues of costs with the patient.
If a client is initiated on therapy for atypical mycobacteria, the same guidelines
for administering the medications to an active case of TB should be followed.
Routine blood tests, vision testing, and screening for side efects and reordering
of medications, are done in the same manner. While TB Control provides the
medications the primary care physician or respirologist assumes the more prominent
role in case management.
123
TREATMENT OF MYCOBACTERIAL DISEASE OTHER THAN TB
ANTI-MYCOBACTERIAL DRUG INFORMATION
Clarithromycin
15 mg/kg up to 1 g
Twice weekly: 25 to 30 mg/
kg usually 1 g
8
th
nerve toxicity (especially
vestibular)
Hypersensitivity
Paraesthesia, peri-oral (not
significant)
Mildly nephrotoxic
Symptoms
BUN
Creatinine
Hearing tests
Vestibular damage
(i.e. check balance and gait)
If renal impairment,
monitor closely.
Reduce dosage in older
clients
In children less than 14
years, after three weeks
daily therapy, reduce dose
or give intermittently.
Not to be used during
pregnancy
Ethambutol
15 to 25 mg/kg
Retro bulbar neuritis
(rare at 15 mg/kg)
Hypersensitivity
Baseline visual acuity and
colour perception monthly
If on long term Ethambutol,
then pt should see an
ophthalmologist or an
optometrist when the above
not available
Client should report any
visual changes to physician
immediately.
Rifampin
usually 600 mg
Hepatotoxicity
Hypersensitivity
GI Upset
Thrombocytopenia
AST/SGOT
Platelet count
Bilirubin
Decreases effectiveness of
the contraceptive pill.
Increases ANTICOAGULANT
drug requirement.
An orange-red
discolouration of sweat,
tears, (may stain soft
contact lenses), urine,
saliva, and feces.
Methadone dose may need
to be increased.
124
APPENDIX I: TB AND HIV
The human immunodefciency virus (HIV) is the single most important promoter
of tuberculosis in those co-infected as it increases their risk about 150 times
compared to those not infected. The HIV virus selectively attacks the CD4 cells
which are extremely important in the normal immune response the body mounts
to prevent the development of active TB disease once infected. Tuberculosis also
presents in a diferent manner in HIV positive patients, in that extrapulmonary
tuberculosis and disseminated disease are more common. Many of the changes
seen on x-ray in the average case of tuberculosis are a result of the immune
response to the organism and depend on intact cell mediated immunity. As this
response is impaired in the co-infected, the x-ray changes can be atypical and
indeed a normal chest x-ray in those with AIDS is not uncommon.
The following issues are relevant to the management of a co-infected case:

All active cases of tuberculosis require an HIV test.

All newly diagnosed HIV positive patients require an assessment for tuberculosis
infection. This can be challenging as HIV positive patients, particularly with
CD4 counts less than 200, may not be able to mount a delayed hypersensitivity
reaction even when infected.
The PPD skin test is generally reliable above a CD4 count of 200 and it is always
worthwhile testing an HIV positive patient. A skin test reaction greater than
5 mm is considered significant. Sputa should be submitted in the appropriate
clinical context such as chronic cough, irrespective of the chest x-ray changes.
Treatment of latent infection is a priority in this group. A standard nine months
Isoniazid regimen is used.
Those diagnosed with active tuberculosis and HIV positivity are generally treated
with antituberculous medications prior to the initiation of antiretroviral therapy.
This simplifies the drug regimen as there are fewer chances for drug interactions.
Normally if the CD4 count is well preserved (greater than 200), completion of the
TB treatment is desirable first.
Those with very low CD4 counts, particularly those with disease attributable to
other opportunistic organisms may require the initiation of antiretroviral sooner.
This decision is usually made in discussion with an HIV specialist.
There is considerable potential for drug interactions particularly with the use
of a rifampin containing regimen along with antiretroviral therapy and close
cooperation is required between TB Control and an HIV specialist.

125
Rifabutin in frequently substituted for rifampin as it has less interactions with
commonly used anti-retrovirals.
The introduction of anti-retrovirals, particularly when the CD4 counts are very
low, runs the risk of what is termed as "the immune reconstitution syndrome".
This can lead to worsening of the clinical picture as the ability of the body to
mount a full immune response is restored. This syndrome can take many clinical
forms and presentations such as worsening of the chest x-ray appearance.
Active disease in the HIV positive patient requires nine months of treatment
irrespective of whether there is advanced disease at presentation.
126
APPENDIX J: MULTIPLE DRUG RESISTANT TUBERCULOSIS (MDR-TB)
MULTIPLE DRUG RESISTANT TUBERCULOSIS (MDR-TB) is defned as persons whose
M. tuberculosis isolates are resistant to Isoniazid and Rifampin, the most efective
drugs in the treatment of tuberculosis.
EXTENSIVELY DRUG RESISTANT TUBERCULOSIS (XDR-TB) is defned as persons
whose M. tuberculosis isolates are resistant to Isoniazid and Rifampin plus resistant
to any fuoroquinolone and at least one of three injectable second line drugs (i.e.
amikacin, kanamycin or capreomycin).
Factors that have contributing to the development of MDR-TB or XDR-TB are:
Clients failing to comply with treatment
Poorly managed TB programs in areas with high default rates
Indiscriminate use of antituberculous medication for other conditions
Antituberculous medication prescribed incorrectly (wrong dose or
inadequate number of effective medications
Poor quality of medication or erratic supply
Malabsorption of medications
Drug resistance is more likely to occur during the early stages of treatment when
the bacillary load is high and a larger number of bacilli are replicating. It is very
unlikely that individuals taking preventative therapy will develop drug resistance
because the population of tubercle bacilli is small and the rate of replication is
slow.
Persons who should be suspected of MDR-TB or XDR-TB are:
Immigrants from countries with high prevalence of MDR-TB or XDR-TB
i.e. China, South Africa, Latvia, previous Soviet Union members
History of treatment in the past
Poor compliance with treatment
History of contact with a drug resistant case
Individuals develop drug resistant forms of tuberculosis in one of two ways:
Acquired resistance is when a person starts off with a fully
sensitive strain of tuberculosis, but due to indiscriminate use of
antituberculous medications develops drug resistance.
Primary resistance is when an individual is infected with a MDR-TB
or XDR-TB strain of tuberculosis.
MDR-TB and XDR-TB are becoming a global problem. XDR-TB has been identifed
in 20 countries. At present, 1 percent of all cases in BC are MDR-TB.
127
TREATMENT
MDR-TB and XDR-TB cases are often dif cult to treat because the second line drugs
are not as efective, and the length of treatment is often 18 months to two years.
The treatment regimen should include at least two drugs that the client has not
yet previously taken. In some instances, surgical intervention may be required.
When a case of MDR-TB or XDR-TB is suspected or identifed, a TB expert should be
consulted regarding the appropriate drug regimen.
PREVENTATIVE TREATMENT FOR CONTACTS

When a contact of a MDR-TB or XDR-TB case is identifed, a TB expert should
be consulted regarding treatment and follow-up. Possible drug regimes combine
Pyrazinamide with a fuoroquinolone or Ethambutol. Close follow-up with chest
x-ray and symptom inquiry is prudent for contacts of drug resistant cases.
128
APPENDIX K: DIRECTLY OBSERVED THERAPY (DOT)
Directly Observed Therapy (DOT) is the observation of the patient by a health care
worker (HCW) or other designated responsible person, as the patient ingests their
tuberculosis (TB) medications.
BACKGROUND
Poor compliance with prescribed TB medications is the most important cause of
treatment failure, relapse and the development of drug resistance. Overcoming this
problem is the primary rationale for DOT. The concept of improving completion
rates with DOT was frst tested in the 1960s. The initial use of DOT with daily
treatment regimens proved to be cumbersome for both the patient and the
health care worker. When intermittent therapy was established as ef cacious,
DOT became more feasible and was ultimately proven to be successful for the
ambulatory treatment of tuberculosis patients. Experience now shows that DOT
ofers the highest rates for completion of therapy, with some studies showing
completion rates approaching 100 percent.
DOT is a strategy which is recommended by the World Health Organization.
Canada is not recognized as a DOT country. TB Control in BC recommends DOT
and DOPT in high risk settings.
WHEN TO USE DOT
Although it is dif cult to predict whether a patient will be compliant with the TB
treatment, most TB programs do not have the resources to provide universal DOT.
Therefore, the use of DOT should be focused on patients in the following settings:
Intermittent dosing regimens
Suspected or known drug-resistant organisms
Treatment history of non-compliance or previous TB
Substance abuse
Mental, emotional, or certain physical impairments that interfere
with ability to self-administer medications
Homeless
TB and HIV co-infection
Children and adolescents (Parents are often delegated to perform
DOT, however this practice requires close monitoring and is not
recommended. Due to the emotional ties some family members
have with the patient, the family may be unwilling to ensure
that the patient takes the medications when the patient resists
treatment)

129
BENEFITS OF DOT
Reduced incidence of treatment failure, relapse, and drug resistance
Decreased period of infectiousness when compared with infectious TB cases who fail
to comply with treatment
Cost efective; the costs of DOT are ofset by potential costs of additional cases and
treatment of drug resistant cases
Early recognition of non-compliance
Early recognition of drug side efects and increased ability to implement quick
adjustments in treatment regimen
Increased interactions between the HCW and patient enhances the ability of the
HCW to:
Establish a supportive and trusting relationship with the patient and
significant others

Get to know hangouts, living quarters, favorite bars, or other favorite
places that can enhance contact tracing

Identify close contacts and arrange TB screening for these contacts

Provide education about TB and TB treatment to the patient and
significant others

Identify lifestyle risks that may afect a patients TB treatment or cure

Monitor and assist with other aspects of treatment such as isolation
precautions, blood work, sputum collection, chest x-rays and other
ordered procedures

Facilitate access to other health care and social services as required
STEPS TO ENSURE SUCCESSFUL DOT
1. Introduce DOT as a positive service. The HCW must recognize DOT as a standard
of care for their patient and not a punishment or penalty. It is important to treat
each patient in a respectful and non-judgmental manner. The HCW should tell the
patient how DOT will help them complete therapy. For example, the HCW may tell
the patient that we will:

Help you remember to take your pills.
Watch closely for side effects.
Reduce your treatment from daily to 2 or 3 times weekly.
Give you and your family opportunity to ask questions.
Help you keep follow-up appointments and arrange appropriate tests
required during treatment.
Encourage and support you until your treatment is complete.
130
2. Assign consistent health care workers to deliver DOT. It has been documented
that the positive relationship fostered by DOT is the main impetus for increased
compliance. Therefore, it is necessary to maintain consistency among those
assigned to deliver DOT.
3. Be fexible in the plan for DOT. Every attempt should be made to accommodate the
patients needs and schedule. The HCW and patient must mutually agree on a
time and location that is convenient and safe.
4. Establish incentives and enablers. For TB patients struggling with issues such as
homelessness, hunger and substance abuse, compliance with TB treatment may be
a low priority. Other patients struggle with the fnancial setback sufered from loss
of work during the period of infectiousness and recovery from TB disease. The use of
incentives and enablers has been extremely efective in increasing compliance and
making the patients experience while on treatment a positive one.
Incentives are defned as small rewards given to a patient (usually with each dose
of medication taken) to encourage them to maintain regular visits for DOT. The
rewards may be varied and need to be tailored to the patients needs and interests.
Examples of incentives may be groceries or food vouchers, bus tokens, holiday gifts,
birthday cards/cakes, personal care items, and games or toys for children.
Enablers are services that remove barriers to a patients participation. Examples
of enablers may be providing for transportation, making individualized
appointments with minimal waiting and creating a pleasant and inviting clinic
atmosphere.
DOCUMENTATION OF TREATMENT

DOT regimens may be daily, twice or three times a week. In order to monitor
compliance and determine completion of treatment, it is important to document
all doses of TB medication taken, all doses missed and all doses self-administered
(i.e. DOT 5 days a week with carries on weekend). Note: intermittent therapy
cannot be self-administered. Depending on the regimen there are usually a
minimum number of observed doses the patient must have before completing the
treatment.
For an example of forms used as medication records for patients on DOT please
refer to Appendix Q forms HLTH 832.
See also DOT Manual link (Appendix Q).
131
APPENDIX L: INTERIM GUIDELINES FOR USE OF IGRA STUDIES
BACKGROUND: IGRAs (Interferon Gamma Release Assays) are new blood tests for the diagnosis of TB infection.
They work on a similar principle to the tuberculin skin test. They cannot distinguish between latent and active TB.
Neither test can rule out TB.
IGRAs currently licensed for use in Canada, are the Quantiferon Gold In-Tube and the T-SPOT.TB test.
ADVANTAGES
Unlike the skin test, IGRAs are not afected by BCG vaccination or the majority of non-tuberculous mycobacteria.
DISADVANTAGES
As new tests, the precise indications for use and interpretation of IGRAs remain uncertain. IGRAs are more costly
than skin testing and require time sensitive laboratory processing.
RECOMMENDATIONS
The tuberculin skin test remains the preferred test for diagnosis of latent TB infection.
In line with the Canadian TB Committee recommendations

the BCCDC supports the use of IGRA in conjunction
with a tuberculin skin test in select circumstances:
1. IGRA may be used to confrm a POSITIVE tuberculin skin test in immunocompetent children (>5 years)
and adults, with prior BCG vaccination, and NO high risk factors for progression to active disease if
infected such as any immunosuppressive therapy, chronic renal failure, or HIV.
2. To increase sensitivity in immunocompromised children (5 years of age and under) and adults with a
NEGATIVE tuberculin skin test and high epidemiologic risk for TB exposure. For example:
o a patient with HIV infection from sub-Saharan Africa
o a patient on dialysis identifed as a contact of an active case
3. Until further evidence is available IGRAs are not recommended for:
o Serial testing, such as health care workers
o Diagnosis of active TB
TO ORDER
At present, IGRAs are only available at BCCDC TB clinics in Vancouver, New Westminister and Victoria and in
hosptial labs in Prince George and Kelowna. To make a referral for IGRA testing and interpretation please contact
these TB clinics.
Vancouver TB Clinic Victoria TB Clinic New Westminster TB Clinic
655 west 12
th
Avenue Central Block, 1952 Bay Street 100-237 East Columbia Street
Vancouver BC, V5Z 4R4 Victoria BC, V8R 1J8 New Westminster, BC V3L 3W4
Tel: 604-707-2692 Tel: 250-519-1503 Tel: 604-707-2698
Fax: 604-707-2690 Fax: 250-519-1505 Fax: 604-707-2694

1
http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/08vol34/acs-6/index-eng.php
132
APPENDIX M: MOLECULAR (DIAGNOSTIC TOOLS)
CLINICAL USES OF GENOTYPING IN BC
Use of laboratory molecular techniques to determine the genotype or
"fngerprint" of M. tuberculosis (MTB) isolates has enhanced our understanding
of TB pathogenesis and transmission. It has been determined that more active
transmission occurs than originally believed despite "low" or falling incidence
rates (i.e. clustering) in Canada. The importance of "casual" contacts and smear-
negative transmission of disease has been demonstrated. In patients with recurrent
TB disease, molecular techniques have shown defnitively that re-infection with a
new MTB strain does occur (exogenous re-infection). Molecular epidemiology has
also confrmed the unusual, but reported, occurrence of simultaneous infection
with multiple diferent strains of MTB. Genotyping has helped to identify and link
previously undetected outbreaks, and confrm epidemiologic linkages in suspected
outbreaks. However, not all clinical isolates require genotyping. Genotyping
should be considered in, but not limited to, the investigation of:
Second Episodes of TB
Suspected Laboratory Cross-contamination
Outbreaks or Suspected Outbreaks
GENOTYPING METHODS

There are a number of diferent genotyping methods available for strain
identifcation of MTB isolates.
IS6110-BASED RESTRICTION FRAGMENT LENGTH POLYMORPHISM

The traditional genotyping method uses restriction fragment length polymorphism
(RFLP) analysis based on the distribution of the insertion sequence IS6110. This
insertion sequence is found exclusively in strains of MTB, is present in multiple
copies and is located in variable positions within diferent isolates. Using this
methodology, investigators can determine whether two isolates of TB have the
same DNA genotype or "fngerprint". Identical DNA fngerprints found by RFLP
analysis in two or more cases of TB suggest recent transmission or epidemiologic
linkage and are described as "clusters".
IS6110-based genotyping is technically demanding, has low throughput and slow
turn-around, requiring isolates to be sub-cultured to obtain suf cient DNA for
testing purposes. For MTB isolates which have fewer than 6 copies of IS6110, RFLP
is unreliable for determining clonality and a secondary typing system such as
spoligotyping should be used. Although newer molecular typing methods have
emerged as valuable techniques, RFLP remains the gold standard due to its greater
discriminatory power, portability and standardization.

133
MYCOBACTERIAL INTERSPERSED REPETITIVE UNIT-VARIABLE NUMBER
TANDEM REPEAT (MIRU-VNTR)
The genome of MTB contains a number of mycobacterial interspersed
repetitive units (MIRU). Using polymerase chain reaction (PCR) and capillary
electrophoresis, MIRU-variable number tandem repeat (MIRU-VNTR) genotyping
determines the number and size of these repeats in each of 12 to 25 independent
loci. As a PCR-based method, MIRU-VNTR genotyping is more rapid than RFLP as
it does not require sub-culturing of MTB isolates. MIRU-VNTR is also amenable
to high-throughput screening of many samples and the digital results simplify
downstream comparative analyses. However, MIRU-VNTR, even in combination
with spoligotyping, does not have the discriminatory power of RFLP.
SPACER OLIGONUCLEOTIDE TYPING (SPOLIGOTYPING)
Spoligotyping is a genotyping method based upon the pattern of specifc spacer
sequences that are found between direct repeat (DR) loci in the MTB genome.
These spacers can have diferent sequences but spacer sequences between 2 specifc
DR loci are conserved among strains. Spoligotyping has less discriminatory
power than IS6110 RFLP, but it is useful as a secondary genotyping method in
conjunction with RFLP or MIRU-VNTR. It can be performed on clinical samples or
with only small amount of DNA, and results can be expressed in digital format for
ease of strain comparison.
STATUS OF GENOTYPING IN BC
Genotyping requests are forwarded to the National Reference Centre for
Mycobacteriology (NRCM) at the National Microbiology Laboratory (NML) in
Winnipeg, Manitoba. Isolates undergo MIRU-VNTR genotyping with the digital
results compared to available patterns in provincial and national computer
databases. If the MIRU-VNTR patterns are identical, RFLP is then completed to
confrm the match. Unique MIRU-VNTR patterns suggest against clustering or
recent transmission.
134
APPENDIX N: IMMIGRATION
All prospective immigrants to Canada are required to have a full medical
examination and chest x-ray to exclude active tuberculosis prior to entering
Canada. Should the patient be found to have active disease, full treatment is
required in the country of origin. The purpose of the examination is to exclude
those with active disease and not to identify people who have latent tuberculosis
infection. A PPD skin test is not a requirement. Testing for syphilis has been in
place for several decades and fairly recently, HIV testing is now required although
this is not generally considered a contraindication to immigration.
The principle components of the immigration process are:
1. Pre-landing assessmen. Refers to the medical examination that is required prior
to granting landed immigrant status and includes the above components. This
examination can occur within Canada, should the patient be applying for landed
immigrant status while in Canada as a visitor. If the chest x-ray is found to be
compatible with active or inactive tuberculosis, a referral is made to TB Control by
the designated medical practitioner (DMP) who performs the medical examination.
Once active disease is excluded, post-landing surveillance is required. Citizenship
and Immigration Canada (CIC) is empowered to ask for any further tests they
deem necessary to arrive at a defnitive diagnosis.
2. Post-landing surveillance. If CIC deems a person requires referral for post landing
follow up, a Medical Surveillance undertaking is issued on arrival in Canada. The
immigrant is required to contact a public health facility which in the province of BC
is TB Control at BC Centre of Disease Control within 30 days of arrival. This does
not mean that they need to be assessed within 30 days, only that they make contact
to provide an accurate address. These referrals are generally seen by appointment
at our facilities in Vancouver, New Westminster, and Victoria. Outside of the lower
mainland, the patients are required to report to their local Public Health Unit. All
the data on the IMM0535 form is entered into TB Controls database at BCCDC.
Public health units outside the lower mainland are notifed by letter from TBC
regarding recent immigrants who require post-landing surveillance. The local HU
then contacts the patient for follow-up.
The main purpose of post-landing surveillance is to identify those immigrants
who might beneft from treatment of latent infection. As most of them will have
chest x-ray abnormalities, this is a particularly relevant group to target for this
intervention as the risks of developing tuberculosis are relatively high within the
frst few years after arrival. The following steps are recommended in the process:
1. Obtain a chest x-ray. Please note, many new immigrants do not have
health care coverage until 3 months post-arrival. For these clients, the
chest x-ray can be completed once their Medical Services Plan (MSP)
is valid. The exception is for those clients who are symptomatic. An
immediate chest x-ray is required and the cost will be covered by TB
Control.
135
2. Take a relevant history of tuberculosis including previous treatment for latent or
active disease, possible sources of exposure to tuberculosis, travel history and
other relevant medical history. This should be documented on the HLTH 939
form and accompany the chest x-ray.
3. Three sputum samples are also usually obtained for acid fast smear and
culture, particularly if there are extensive changes on the chest x-ray.
This is done to exclude active disease prior to ofering the patient
preventative treatment. PPD skin test is not routinely administered
unless requested.

NOTE: Collect 3 sputum for AFB smear and culture at frst visit, regardless
if client needs to wait 3 months for MSP coverage.
4. TB Control will send for the relevant documents and chest x-rays
performed for the pre-landing immigration medical examination.
5. Once these are reviewed, follow up recommendations will be made for
each individual patient based on risk factors.
REFUGEES
Refugees come to Canada as either 'convention refugees' who normally have had
a physical examination and chest x-ray overseas or they come as refugees who
declare themselves only at arrival in Canada at a port of entry. Non-convention
refugees require an examination similar to the pre-landing immigration process
and these are usually handled at designated facilities such as the Bridge Clinic in
Vancouver. All costs of the medical examination for refugees are covered by the
Interim Federal Health Program administered in Ottawa prior to qualifcation
for provincial health care coverage. If anything more than routine examinations
are required for a refugee, permission to proceed must frst be obtained from the
Interim Federal Health program (www.fasadmin.com).
136
Tuberculosis Field Operations
655 West 12
th
Avenue Tel 604 707 2697
Vancouver, British Columbia Fax 604 707 2690
Canada V5Z 4R4 www.bccdc.ca
May 6, 2010
NORTH OKANAGAN HEALTH UNIT
LUMBY, BC
RE: VILLARANTE, FAMIE CONIENDO
PO BOX 640
LUMBY, B.C. V0E 2G0
DOB: 1952-04-14
Phone: 250-
Place of origin: MANILA
Date of arrival: MAR. 9, 2010
Immigration File: T531111549
MAN090028826/B050133220
Citizenship and Immigration, Canada has notified the Division of Tuberculosis Control of
the recent arrival of the above named. Immigration has determined that this person has a
diagnosis of Inactive Pulmonary Tuberculosis. If the client is asymptomatic, have them
submit sputum x 3 and x-ray in 3 months when they should have medical coverage. As
well, please obtain the name of the family physician for our records. If the client is
symptomatic, have them submit sputum X3 and have an x-ray NOW. If they dont have
MSP coverage or are not able to pay, indicate on 939 form to bill TB Control.
Please let me know as soon as possible if unable to locate.
Thank you for your assistance in this matter.
A research and teaching centre affiliated with UBC
Yours truly,
R. K. Elwood, M.B., M.R.C.P.(UK), F.R.C.P.(C)
Provincial Director
RKE:yd
May 16, 2010
NORTH VANCOUVER ISLAND HEALTH UNIT,
CAMPBELL RIVER, BC
RE: MOUSE, Minnie (Mrs)
Walt Disney Parade
California.
DOB: 1936-**-**
Phone: unlisted
Place of origin: Disney Land, Sacramento, USA
Date of arrival: JUNE 4, 2010
Immigration File: ***********
****************************
Citizenship and Immigration, Canada has notified the Division of Tuberculosis Control
of the recent arrival of the above named. Immigration has determined that this person
has a diagnosis of Inactive Pulmonary Tuberculosis. If the client is asymptomatic, have
them submit sputum x 3 and x-ray in 3 months when they should have medical coverage.
As well, please obtain the name of the family physician for our records. If the client is
symptomatic, have them submit sputum X3 and have an x-ray NOW. If they dont have
MSP coverage or are not able to pay, indicate on 939 form to bill TB Control.
Please let me know as soon as possible if unable to locate.
Thank you for your assistance in this matter.
Yours truly,
R. K. Elwood, M.B., M.R.C.P.(UK), F.R.C.P.(C)
Provincial Director
RKE:yd
137
APPENDIX O: TUBERCULOSIS AND CHRONIC RENAL FAILURE
CHRONIC RENAL FAILURE (CRF) is defned as:
Kidney damage present for 3 months or longer as defined by
structural or functional abnormalities of the kidney with or
without decreased glomerular filtration rate (GFR)
GFRs below 60 for 3 months or longer with or without kidney damage
DIALYSIS is defned as:
A procedure used to remove toxic wastes from the blood of a patient
with acute or chronic Renal Failure. The blood may be circulated
outside the body in a Hemodialyzer, called Hemo-Dialysis, or
through the peritoneal cavity, called Peritoneal Dialysis.
Chronic renal failure impairs immune function and is associated with an increased
incidence of tuberculosis (TB). Among patients with CRF requiring dialysis, rates of TB
10 25-fold greater than those in the general population have been reported in Canada.
Factors contributing to the higher incidence of TB among CRF patients include:
CRF patients are more likely to be elderly or to have migrated from
countries with a high prevalence of TB
CRF patients with latent TB are more likely to progress to active TB
because of impaired cell-mediated immunity.
Many CRF patients have diabetes or other medical conditions that
are also known risk factors for developing active TB.
Local research on the risk of TB in dialysis patients with an aging population, and
increasing migration of immigrants from countries with a high prevalence of TB,
it is strongly recommended that screening of this population and implementation
of preventive treatment be considered.
The following considerations provide support for the routine TB screening of CRF
patients prior to or upon starting dialysis:
The risk of active TB disease appears to be particularly high in the first 6
to 12 months after initiating dialysis.
The diagnosis of active TB is difficult because CRF patients are more
likely to have extra-pulmonary disease and symptoms such as malaise,
anorexia, weight loss, and fever are attributed to complications of CRF.
Delayed TB diagnosis contributes to a high mortality rate among CRF
patients.
Delayed TB diagnosis in patients being dialyzed in a facility increases
the risk of TB transmission to extremely vulnerable patients and
facility staff.
Treatment of active TB in CRF patients is more difficult because several
TB medications are eliminated by the kidney and therefore require
regimen adjustments.
138
RECOMMENDATIONS FOR TB SCREENING OF PATIENTS WITH CRF

Because of the increased risk of developing TB, it is recommended that patients with Chronic
Renal Failure be screened for latent TB infection. TB screening should include TB skin testing,
or if accessible, IGRA testing (see Appendix L), and a chest x-ray prior to or upon initiation of
dialysis treatment.
Recommendations for LTBI treatment in patients with CRF:
Isoniazid 9 months DOT on dialysis
Rifampin 4 months interactions with transplant medications
139
APPENDIX P: SPUTUM INDUCTION AT VANCOUVER TB CLINIC
PURPOSE: Sputum induction is a technique used to obtain sputum for laboratory
evaluation from patients who have dif culty producing sputum spontaneously.
During the sputum induction procedure, the patient inhales an aerosolized mist
of hypertonic saline. The nebulized saline hydrates the patients secretions while
also causing irritation of the airway, promoting coughing and the production
of respiratory secretions. Clients who have a history of Asthma or COPD are at
increased risk of bronchspasm and sputum induction is not recommended (but can
use Ventolin).
COLLECT ALL NECESSARY EQUIPMENT:
Nebulizer Mask Kit
3% hypertonic saline or isotonic saline
Tissues
Sterile sputum container, Lab requisition, plastic zip lock bag
N95 mask
Ventolin Puffer (in the event the client becomes bronchospastic)
PREPARATION OF THE EQUIPMENT:
1. Turn on the local exhaust ventilator device and verify that air is
flowing into sputum-induction booth/room. Check compressor
devices that create an aerosol with compressed air.
2. Pour 35 ml of hypertonic saline (3%Nacl) into the nebulizer.
3. Test nebulizer to ensure that adequate mist is produced.
PREPARATION OF PATIENT:
Explain:
Purpose of procedure
How to use the nebulizer
How to notify nurse if assistance is needed or when procedure is completed.
Importance of staying in the booth until coughing has stopped.
Importance of replacing mask before leaving booth.
Remind patient not to begin the sputum induction procedure until the door of the
booth is closed.
Instruct patient to:
Inhale mist with deep breaths
Cough vigorously if spontaneous coughing does not occur. Cover mouth with tissue
when coughing, unless expectorating into a jar.
Continue to cough until 5 to 10 ml of sputum have been obtained.
140
During procedure:
Observe; through the glass window at all times during the procedure for signs of
respiratory distress and ensure that the patient does not leave the room until
coughing has stopped.
After obtaining the sputum sample, ensure patient has stopped coughing before
leaving the booth.
If the patient must leave the room before the coughing has stopped, ensure the
patient is masked.
After obtaining the sputum sample, ensure patient has stopped coughing before
leaving the booth.
Suspected or confirmed TB patients, should put the mask on before leaving the
sputum induction booth.
After the procedure:
Ensure the door is closed after the patient completes the procedure.
Put a sign on the door indicating when the room will be safe to enter.
Allow 20 to 30 minutes for removal of at least 99 per cent of airborne
contaminants.
Remove and discard disposable items.
Wipe counter/table top with Accel TB swipes.
141
APPENDIX Q: FORMS & MANUALS (LINKS)
Completion of Treatment with TB Medications Form (pdf)
Decision Support Tools TST (pdf)
DOT Manual (pdf)
Follow-up Contact Assessment TB Control HLTH 836 (s)
Tuberculosis Medication Reorder Form (pdf)
Mycobacteriology and TB Requisition Form
Notification of Abnormal AST Form (pdf)
Office Products Centre Customer Order Form (DCV)
PharmaNet Patient Consent to Access Form
PPD Antigen and BCG Vaccine Order Form
Preventative Therapy Request Form (pdf)
Record of Supervised TB Medications HLTH 832
Requisition for Specimen Containers (sputum bottles)
TBSAC Monthly Report Form HLTH 8771
Tuberculosis Screening Program HLTH 939 form
Tuberculosis Starter Unit Drug Order Form

BCCDC TB ManualRevisedFebruary 2012

Transféré par

Informations du document

Description originale:

Copyright

Formats disponibles

Partager ce document

Partager ou intégrer le document

Options de partage

Avez-vous trouvé ce document utile ?

Ce contenu est-il inapproprié ?

Droits d'auteur :

Formats disponibles

BCCDC TB ManualRevisedFebruary 2012

Transféré par

Droits d'auteur :

Formats disponibles

TB Manual

February 2012 | For professionals to help manage tuberculosis

Vous aimerez peut-être aussi