Literature review

Historical aspects
Tuberculosis is an ancient disease, an evidenced the skeletal remains of Neolithic, pre-
Columbian and old kingdom Egyptians person. This disease referred to as “consumption”
in early Hindu writings and as “phthisis” by the Greeks.
Tuberculosis (abbreviated as TB for tubercle bacillus or Tuberculosis) is a common and
deadly infectious disease caused by mycobacterium, mainly mycobacterium tuberculosis.
One third of the world’s current population has been infected by TB, and new infections
occur at a rate of one per second. Not every one infected develops the full blown disease,
asymptomatic, latent infection is most common. However, one in ten latent infections will
progress to active disease which if left untreated kills more than half of its victims.
The study of tuberculosis dates back to THE CANON OF MEDICIN written by IBN-A-
SINA (Avicenna) in 1020’s. He was the first physician to identify pulmonary tuberculosis
as a contagious disease, the first to recognize association with diabetes, and the first to
suggest that it could spread through contact with soil and water. He developed the method
of quarantine in order to limit the spread of tuberculosis.
Although it was established that the pulmonary form was associated with ‘Tubercles’ by
Dr. Richard Morton in 1689, due to the variety of its symptoms, TB was not identified as a
single disease until the 1820’s and was not named ‘tuberculosis’ until 1839 by J. L.
Schonlein. During the years 1838 to 1845, Dr. John Croghan, the owne4r of mammoth
cave brought a number of tuberculosis sufferers into the cave in the hope of curing the
disease with a constant temperature and purity of the cave’s air: they died within a year.
The first TB sanitorium opened in 1859 in Gorbersdorf, Germany (today’s sokolowsko,
Poland) by Herman Brehmer. In regard to this claim ‘THE TIMES’ for January 15, 1859
page 5 column 5 carries an advertisement seeking funds for the Bournemouth sanatorium
for consumption, referring to the balance sheet for the past year, and offering an annual
report to prospective donors, implying that this sanatorium was in existence at least in
1858. The bacillus causing tuberculosis, mycobacterium tuberculosis, was identified and
described on march 24, 1882 by Robert koch. He received the noble prize in physiology or
medicine in 1905 for this discovery. Koch did not believe that bovine (cattle) and human
tuberculosis were similar which delayed the recognition of infected milk as a source of
infection. Later this source was eliminated by the pasteurization process. Koch announced
a glycerin extract of the tubercle bacilli as a “remedy” for tuberculosis in 1890, calling it
“TUBERCULIN”. It was not effective but was later adopted as a test for pre symptomatic
tuberculosis.

TUBERCULOSIS - DEFINITION

“Tuberculosis is a chronic bacterial infection caused by mycobacterium tuberculosis that is

characterized by formation of granulomas in the infected tissues and by cell mediated
hypersensitivity. The usual site of the disease is lungs, but other organs may be involved”

TUBERCULOSIS - CLASSIFICATION
 Pulmonary tuberculosis is most common form of the disease.

 Extra pulmonary is tuberculosis affecting organs other than the lungs, most
commonly pleura, lymph nodes, spine, joints, genitourinary tract, nervous system
or abdomen. tuberculosis may affect any part of the body.

TUBERCULOSIS - GLOBAL BURDEN

According to WHO, 2 billion people- one third of world’s population- have been
exposed to the tuberculosis pathogen. Annually, 8 million people become ill with
tuberculosis, and 2 million people die of the disease world wide. In 2004, around 14.6
million people had active TB disease with 9 million new cases. The annual incidence
rate varies from 356/100,000 in Africa 241/100,000 in the America. TB is the world’s
greatest infectious killer of women of reproductive age and the leading cause of death
among people with HIV/AIDS.
In 2005 the country with the highest estimated incidence of TB was Swaziland, with
1262 cases per 100,000 people. India has the largest number of infections, with over
1.8 million cases. In developed countries, tuberculosis is less common and is mainly
an urban disease. In United Kingdom, TB incidences range from 40/100,000 in
London to less than 5/100,000 in the rural south west of England; the national average
is 13/100,000. The highest rates in Western Europe are in Portugal (42/100,000) and
Spain (20/100,000). These rates compare with 113 per 100,000 in China and 64 per
100,000 in Brazil. In the United States the over all tuberculosis case rate was
4.9/100,000 persons in 2004.
The incidence of TB varies with age. In Africa, TB primarily affects adolescents and
young adults. However, in countries where TB has gone from high to low incidence,
such as the United States, TB is mainly a disease of older people.

TUBERCULOSIS - NATIONAL BURDEN

Tuberculosis is a major public health and developmental problem in Pakistan. The

country has 7th highest burden of TB among the 22 high burden tuberculosis countries
worldwide, according to the WHO Global TB report 2006. Every year, approximately
280,000 people develop TB with an incident rate of 181/100,000 and 62,000 people
die of TB in the country with a mortality rate of 37/100,000. 1 TB case is responsible
for 5.1% of the total national disease burden which is 3rd largest contribution to the
disease burden in Pakistan.

TUBERCULOSIS - MODE OF TRANSMISSION

The microorganisms usually enter the body by inhalation through the lungs. They
spread fron the initial laocation of the lungs to other parts of body via the blood
stream, the lymphatic system, the airways or by direct extension to other organs.

TUBERCULOSIS - ETIOLOGY

Mycobacterium tuberculosis, is the causative organism. Along with the closely related
M. bovis, it causes tuberculosis. Mycobacterium is distinguished by their surface lipids
which render them acid fast so that they can not be decolorized with acid alcohol.

TUBERCULOSIS - PATHOGENESIS

The tuberculosis is spread principally by inhalation of expectorated droplet nuclei

containing bacilli. Rarely, infection is acquired by drinking milk containing M. bovis
or by traumatic inoculation into the skin. Depending upon the pathology tuberculosis
is divided into primary and post primary tuberculosis.

PRIMARY TUBERCULOSIS

The initial lesion of tuberculosis develops before specific cell mediated immune
reaction develop to contain the infection.
A peripheral lesion with enlarged hilar lymph nodes on the chest radiology is
diagnostic for primary complex. Tuberculin conversion usually occurs 3-8 weeks from
the time of infection. Bacteriological confirmation by gastric washing, laryngeal swab
or bronchoscopy may yield the diagnosis.
The initial infection, whether, or not it causes overt disease, may resolve completely by
or merely progress to post primary disease in some time in future.

POST PRIMARY TUBERCULOSIS

It occurs in the previously infected, usually tuberculin positive, person as a result of

endogenous reactivation of a dormant infection or of exogenous re-infection. For
unknown reasons, lesion usually develops in the upper part of the lung. Necrosis is
prominent, resulting in large solid lesions (tuberculoma) and cavities. The local lymph
nodes are not usually involved and hematogenous dissemination is rare, except in the
immunocompromised.

EXTRA PULMONARY TUBERCULOSIS

Extra pulmonary is tuberculosis affecting organs other than the lungs, most commonly
pleura, lymph nodes, spine, joints, genitourinary tract, nervous system or abdomen.
tuberculosis may affect any part of the body.

TUBERCULOSIS - DIAGNOSIS

HISTORY

 Persistent cough for three weeks or more

 Sputum production which may be blood stained (haemoptosis), shortness of
breath and chest pain.
 Fatigue, loss of appetite and loss of weight, night sweats and fever.
BACTERIOLOGICAL EXAMINATION OF SPUTUM

When ever tuberculosis is suspected three specimens must be collected for examination by
microscopy. When ever possible, they should be obtained within 24 hours as follows:
First Specimen
At the first interview with the patient a spot specimen is collected; this specimen is
obtained on the spot, after coughing and clearing the back of the throat, under supervision
of a staff member, in a well ventilated area.
Second Specimen
The patient is then given a sputum container for collection of an early morning specimen
before the second interview, which should be on the next working day.
Third Specimen
At the second interview with the patient, the collection specimen is brought by the patient
and a further spot specimen is obtained.
Should the first spot specimen be positive and should the patient not return for the second
interview, an immediate search must be made to find the patient in order to prevent
transmission of microorganisms in the community and deterioration in the patient’s
conditions.
Sputum for Culture
Sputum can also be cultured for mycobacterium tuberculosis but it takes about six weeks.

TUBERCULIN SKIN TEST

It can be used in individual patients to detect TB infection as well as in screening of high

risk population to guide TB control efforts. The tuberculin skin test is a very safe,
inexpensive, and readily available but only a crude indicator of delayed hypersensitivity
following infection by mycobacteria. A positive tuberculin test indicates an intact cell
mediated immunity and consists of an infiltration with CD4+T lymphocytes, macrophages
and local edema after injection of tuberculin protein. The most accurate tuberculin test is
the ‘Montoux test’ on the volar aspect of the fore arm. After strictly intradermal injection
of 0.1ml tuberculin solution with single use syringes an in duration can be detected within
48 to 72 hours.
False negative tuberculin tests, defined as indurations equal or smaller than 10mm, or
found in 15 to 25% of patients with active tuberculosis. False negative test are caused by
older age, lower serum protein (malnutrition or alcoholism), concomitant illness such as
viral infection, HIV or sarcoidosis and over whelming TB disease and Technical reasons.

Effective TB Control (DOTS)

The WHO-recommended treatment strategy for detection and cure of TB is "Directly

Observed Treatment, Short-course" (DOTS). DOTS combines five elements: political
commitment, microscopy services, drug supplies, surveillance and monitoring systems and
use of highly efficacious regimes with direct observation of treatment.

Once patients with infectious TB (bacilli visible in a sputum smear) have been identified
using microscopy services, health and community workers and trained volunteers observe
and record patients swallowing the full course of the correct dosage of anti-TB medicines
(treatment lasts six to eight months). The most common anti-TB drugs are isoniazid,
rifampicin, pyrazinamide, streptomycin and ethambutol.

Sputum smear testing is repeated after two months, to check progress, and again at the end
of treatment. A recording and reporting system documents patients' progress throughout,
and the final outcome of treatment.

• DOTS produces cure rates of up to 95 percent even in the poorest countries.

• DOTS prevents new infections by curing infectious patients.
• DOTS prevents the development of MDR-TB by ensuring the full course of
treatment is followed.
• DOTS strategy as one of the "most cost-effective of all health interventions."

Since DOTS was introduced on a global scale, millions of infectious patients have
received effective DOTS treatment. In half of China, cure rates among new cases are 96
percent. In Peru, widespread use of DOTS for more than five years has led to the
successful treatment of 91 percent of cases.

By the end of 1998, all 22 of the high burden countries which bear 80% of the estimated
incident cases had adopted DOTS. 43 percent of the global population had access to
DOTS, double the fraction reported in 1995. In the same year, 21 percent of estimated TB
patients received treatment under DOTS, also double the fraction reported in 1995.