Tuberculosis

By: Laurence Gerard A. Aberia

06.22.2013

Case of JZ
36 y/o unmarried man from RI Recently released from state prison Does carpentry for a living

Lives with a distant cousin in a bungalow

Case of JZ
Complained of the ff at the ER: 1.)Hemoptysis secondary to persistent coughing over the last month 2.) Pain during exhalation and inhalation 3.) Fatigue 4.) Decreased appetite

Introduction
Tuberculosis (TB) is caused by bacteria of the Mycobacterium tuberculosis complex Lungs are usually affected although other organs may be involved as well One of the oldest diseases known to affect humans

Remains to be one of the major causes of death worldwide

Etiology
M. tuberculosis is a rodshaped, non-spore-forming, thin aerobic bacterium measuring 0.5 m by 3 m. Acid-fast bacilli

Complete genome sequence of M. tuberculosis comprises 4043 genes encoding 3993 proteins and 50 genes encoding RNAs
High guanine + cytosine content (65.6%) is indicative of an aerobic lifestyle.

Epidemiology
More than 2B (1/3 of world pop.) are estimated to be infected with TB Most cases come from developing countries in Asia, Africa, and in the Middle East Global incidence peaked around 2003 and now appears to be declining slowly In 2010 8.8M ill; 1.4M died

Epidemiology
Commonly transmitted by droplet nuclei which are aerosolized by coughing, sneezing, or speaking There may be as many as 3000 infectious nuclei per cough

Epidemiology
Determinants of transmission: 1.) Probability of contact 2.) Intimacy & duration of contact 3.) Degree of infectiousness 4.) Shared environment

Epidemiology
Pts whose sputum contains AFB visible by microscopy are the most likely to transmit the infection Most infectious pts: pts who have cavitary pulmonary disease, and pts who have laryngeal TB

Pts with extrapulmonary disease are nonifectious

Epidemiology
The risk of developing disease depends largely on the individuals innate immunologic and nonimmunologic defenses Clinical illness directly following infection: Primary TB common among children & immunocompromised persons Primary TB is not generally associated with high-level transmissibility despite its severity

Dormant bacilli: Secondary TB / Postprimary TB

Secondary TB is more infectious b/c of frequent cavitation

Pathogenesis and Immunity

Inhalation of nuclei containing microorganism from infectious pt: signals the interaction of M. tuberculosis with the human host Complex series of events happen that ensure the survival of the bacilli within the phagosomes

If the bacilli are successful in arresting phagosome maturation, replication begins

What makes TB so dangerous?

CNC
Coalesce Necrosis Cavity

Clinical Manifestations
TB may be classified as:
Pulmonary Extrapulmonary Both pulmonary and extrapulmonary

Clinical Manifestations Pulmonary TB

Primary Disease
Occurs soon after the initial infection with tubercle bacilli Middle and lower lung zones are involved

Postprimary Disease
Results from endogenous reactivation of latent infection Localized to the apical and posterior segments of the upper lobe A.K.A:
Adult-type Reactivation Secondary TB

Lesions formed are peripheral

May progress rapidly to clinical illness

Clinical Manifestations Extrapulmonary TB

In order of frequency, the extrapulmonary sites most commonly involved in tuberculosis are:
Lymph nodes Pleura Genitourinary tract Bones & Joints Meninges Peritoneum Pericardium

Clinical Manifestations Extrapulmonary TB: Lymph-Node

Presents as painless swelling of the lymph nodes, most commonly at posterior cervical and supraclavicular sites scrofula (lymphadenitis) Most common type of EPTB Frequent among HIV-infected patients

Clinical Manifestations Extrapulmonary TB: Pleura

Result from either:
contiguous spread of parenchymal inflammation accompanying postprimary disease, actual penetration by tubercle bacilli into the pleural space

Clinical Manifestations Extrapulmonary TB: Upper Airways

A complication of advanced cavitary pulmonary tuberculosis may involve the larynx, pharynx, and epiglottis Symptoms include:
hoarseness, dysphonia, and dysphagia productive cough

Clinical Manifestations Extrapulmonary TB: Genitourinary

involve any portion of the genitourinary tract Common presentations: urinary frequency, dysuria, nocturia, hematuria, and flank or abdominal pain Pts may be asymptomatic Female > Male

Clinical Manifestations Extrapulmonary TB: Skeletal

In bone and joint disease, spread from adjacent paravertebral lymph nodes Weight bearing joints are most commonly affected

Clinical Manifestations Extrapulmonary TB: Meningitis and Tuberculoma

Results from the hematogenous spread of primary or postprimary pulmonary disease or from the rupture of a subependymal tubercle into the subarachnoid space Paresis of cranial nerves

Lumbar puncture is the cornerstone of diagnosis

Clinical Manifestations Extrapulmonary TB: Gastrointestinal

Uncommon Various pathogenetic mechanisms are involved:
Swallowing of sputum with direct seeding Hematogenous spread Ingestion of milk from cows affected by bovine tuberculosis

Ileum and Cecum are the most common sites involved

Clinical Manifestations Extrapulmonary TB: Pericardial

Often a disease of the elderly and those with HIV Due to direct progression of a primary focus within the pericardium, to reactivation of a latent focus, or to rupture of an adjacent subcarinal lymph node

Clinical Manifestations Extrapulmonary TB: Miliary/Disseminated

Due to hematogenous spread of tubercle bacilli Lesions: yellowish granulomas that resemble millet seeds Eye examination may reveal choroidal tubercles Rare presentation seen in the elderly: cryptic miliary TB, which has a chronic course involvement preceding death

Clinical Manifestations Extrapulmonary TB: HIV associated

Common occurrence among HIV patients A new tuberculosis infection acquired by an HIV-infected individual may evolve to active disease in a matter of weeks rather than months or years

Diagnosis of TB
The diagnosis is first entertained when the chest radiograph of a patient is abnormal

Diagnosis of TB AFB Microscopy

Based on the finding of AFB on microscopic examination of a diagnostic specimen, such as a smear of expectorated sputum or of tissue

Diagnosis of TB Mycobacterial Culture

Specimens may be inoculated onto egg or agar-based medium and incubated at 37*C 4 8 weeks before growth is detected

Diagnosis of TB Nucleic Acid Amplification

Permit the diagnosis of tuberculosis in as little as several hours, with high specificity and sensitivity approaching that of culture most useful for the rapid confirmation of tuberculosis in persons with AFBpositive specimens

Diagnosis of TB Drug Susceptibility Testing

Initial isolate of M. tuberculosis should be tested for susceptibility to isoniazid, rifampin, and ethambutol Conducted directly (with the clinical specimen) or indirectly (with mycobacterial cultures) on solid or liquid medium

Diagnosis of TB Radiographic Procedures

Abnormal chest radiographs The classic picture is that of upper lobe disease with infiltrates and cavities CT for questionable findings on plain chest radiography MRI for intracranial TB

Diagnosis of TB Tuberculin Skin Testing

Used in screening for latent TB infection Positive result: firm red bump at the site w/in 2 days How its done:
Injection of small amount of TB protein on the top layer of the skin on inner forearm

Management
Two aims of TB treatment:
1.) Interrupt TB transmission by rendering pts nonifectious 2.) Prevent morbidity and death by curing pts with TB

Management
Four major drugs are considered the firstline agents for the treatment of TB:
1.) isoniazid 2.) rifampin 3.) pyrazinamide 4.) ethambutol

Well absorbed after oral administration 6 9 months regimen

Management
isoniazid, rifampin, pyrazinamide, and ethambutol were chosen on the basis of their: 1.) bactericidal activity 2.) sterilizing activity 3.) low rate of induction of drug resistance

Management
Bacteriologic evaluation is the preferred method of monitoring the response to treatment for TB

Pts with pulmonary disorders: sputum examination until it becomes negative Pts with extrapulmonary tuberculosis: difficult and often not feasible

Management
Some strains of TB that become resistant to drugs arise by spontaneous point mutations in the mycobacterial genome Drug resistant TB: occurs at a low, but predictable rate

Management
During treatment, pt should be monitored for drug toxicity Common adverse effect: hepatitis Hypersensitive reactions usually require the discontinuation of all drugs

Management
Treatment failure: suspected when a pts sputum culture remains positive after 3 months, or if AFB smears remain positive after 5 months The mycobacterial strains infecting pts who experience relapse after apparent successful treatment are less likely to have acquired drug resistance

Management
Best way to prevent TB: diagnose and isolate infectious cases rapidly and administer treatment until pts are rendered noninfectious

OT Management
Arts and crafts