1. INFECTIOUS DISEASE
Tuberculosis (TB) is responsible for over 2 million deaths annually. The human immunodeficiency virus type 1 (HIV-1) epidemic has significantly
contributed to the resurgence of TB worldwide, with HIV-1 infection being the most potent risk factor for the development of active TB.The emergence
of multi–drug-resistant TB is a worldwide problem and threatens efforts to control the disease. The bacterial organism can cause disease in virtually
any organ, but the lungs are predominantly affected. Effective chemotherapy is available to cure virtually all cases of TB. Global strategies are
focused on halting the spread of TB and curing infectious cases.
HISTORY Mycobacterium tuberculosis CHARACTERISTICS
TB is one of the oldest diseases known to man, as evidenced by findings of TB spinal disease within Egyptian M. tuberculosis contains many
mummies dating back to 4000 to 2000 BC. During the time of Hippocrates, pulmonary TB was called phthisis by the immunoreactive substances, like
Greeks (“consumption”) because the disease caused a general wasting.During the industrialization and urbanization surface lipids and water-soluble
of the 17th and 18th centuries in Europe, the incidence of TB rose significantly to epidemic proportions. In the mid-
components of cell wall peptidoglycan,
19th century, mortality rates in eastern cities in the United States averaged 400 per 100,000 population.TB proliferates
3. Preparation of extracts
in crowded, unsanitary, urban conditions, and improvements in these socioeconomic conditions have led to declining
to exert their effects through primary
TB rates.The infectious etiology of TB was debated until Robert Koch, in 1882, identified the tubercle bacillus as the actions on host macrophages.
cause of human TB.This led to the development of basic TB disease control strategies like the creation of the Mycobacteria contain several protein
sanatorium movement in Europe (1854) and in the United States (1882) to isolate infectious individuals; the use of and polysaccharide antigens that are
pasteurization of cow's milk (virtually eliminating human disease caused by Mycobacterium bovis); the creation of involved in the pathogenesis of
bacille Calmette-Guérin (BCG) vaccine; and, in the 1940s, the discovery of anti-TB drugs disease.
EPIDEMIOLOGY TRANSMISSION
TB remains one of the deadliest diseases in the world. Eight million M. tuberculosis is acquired by inhalation of infectious airborne particles, called droplet nuclei, that are
new TB cases are estimated to occur each year in the world; most of small enough (1 to 5 µm) to reach the alveolar air spaces. Patients with active pulmonary or laryngeal
them occur in developing countries where resources to treat infected TB expel these airborne droplets primarily by coughing, sneezing, or vocalizing; the particles can
individuals are limited and HIV infection is common. Within the past remain suspended in the air for several hours, allowing exposure to a susceptible person (contact) and
10 years, it has become clear that the spread of HIV infection entry into the terminal air passages. Factors that determine the probability of infection are the intimacy
worldwide and the immigration of persons have resulted in increased and duration of that contact, the degree of infectiousness of the case, and host defenses. Crowded
number of TB cases worldwide. areas with poorly ventilated rooms favor the transmission of TB.
POPULATIONS AT RISK PATHOGENESIS
Latent infection occurs when the tubercle bacilli are inhaled into the body. After inhalation, the
droplet nuclei containing M. tuberculosis settle into the bronchioles and alveoli of the lungs.
Development of infection in the lung is dependent on both the virulence of the organism and the
inherent microbicidal ability of the alveolar macrophages. In the nonimmune (susceptible) host,
the bacilli initially multiply unopposed by normal host defense mechanisms. The organisms are
then taken into alveolar macrophages by phagocytosis and may remain viable, multiplying within
the cells for extended periods of time. After 14 to 21 days of replication, the tubercle bacilli spread
via the lymphatic system to the hilar lymph nodes and through the bloodstream to other organs.
Certain organs and tissues in the body, such as the bone marrow, liver, and spleen, are resistant to
subsequent multiplication of these bacilli. In contrast, organs with high blood flow and PaO2, such
as the upper lung zones, kidneys, bones, and brain, are particularly favorable for growth of the
organisms. The organisms replicate for 2 to 12 weeks until they reach 103 to 104 in number, then a
specific T-lymphocyte–mediated immune response develops.
CLINICAL MANIFESTATIONS Tuberculin skin testing (TST)
Pulmonary Tuberculosis Identifies persons at high risk for developing TB who would benefit from treatment of latent
It can be further categorized as primary or postprimary tuberculosis infection (LTBI) if detected. This skin test is of limited value in the diagnosis of active TB
due to its low sensitivity and specificity. The focus on high-risk groups has led to the term “targeted
(secondary). Primary TB results from initial infection occurs in
tuberculin testing” to promote directed activities.
areas of high TB prevalence.This form of pulmonary disease
often occurs in children, with localization in the middle and lower MANTOUX METHOD
lung zones. Lesions form after infection,mostly the lesions heal Intradermal injection of 0.1 mL of 5 tuberculin units (TU) of purified protein derivative (PPD) into the
spontaneously. Children with impaired immunity may progress to dorsal or volar surface of the forearm. The reaction to the injected tuberculin is a DTH response,
clinical illness. which should be examined and interpreted by a trained health care provider 48 to 72 hours after test
administration. By gentle palpation of the indurated area, the transverse diameter of the induration is
Postprimary disease is also referred as adult-type or reactivation
measured; erythema should be excluded from the measurement.Three cut-off levels have been
and occurs most frequently from reactivation of remotely acquired recommended for defining a positive TST: 5 mm or more for persons at highest risk for developing
latent infection. This form of pulmonary disease tends to be TB disease, 10 mm or more for persons at high risk, and 15 mm or more of induration for persons at
localized to the apical and posterior segments of the upper lobes. low risk . If a person has a negative TST reaction and upon a repeat TST within 2 years an increase in
The extent of lung involvement varies considerably, from minimal reaction size of at least 10 mm occurs, the result should be interpreted as skin conversion due to
clinical illness barely discernible on chest radiographs to major recent infection.No method can distinguish between tuberculin reactions caused by vaccination with
involvement with extensive cavitation and debilitating symptoms. the TB vaccine (BCG) and those caused by infection due to M. tuberculosis.
Early in the course of postprimary disease, nonspecific findings
AFB MICROSCOPY
usually present insidiously with symptoms such as fever, chills,
Three sputum specimens should be collected and submitted to the laboratory for
and night sweats, weight loss, anorexia and general malaise.
microscopic examination for AFB smear and mycobacteriology culture. Sputum
Cough eventually develops in most patients; it may be
induction with hypertonic saline may be necessary to obtain specimens in persons
nonproductive initially and then may become productive with
unable to produce sputum. Microscopic examination of specimens such as sputum or
purulent sputum.
tissue that reveal AFB provides strong inferential evidence for the diagnosis of TB. A
Extrapulmonary Tuberculosis
lack of positive acid-fast smears does not rule out presumptive TB, because smears
It may occur at sites such as the lymph nodes, genitourinary
may be negative.When extrapulmonary TB is suspected, a variety of clinical specimens
tract, pleura, bone and joints, spine, peritoneum or meninges.
other than sputum (urine, cerebrospinal fluid, pleural fluid, pus, or biopsy specimens) .
Infection at extrapulmonary sites is much more common in HIV-
infected persons than in the non-HIV-infected population (30% to MYCOBACTERIAL CULTURE
50% versus 15%) because of immunosuppression and the failure M. tuberculosis is a slow-growing organism, the conventional culturing technique takes several
of the immune system. Clinical manifestations of disseminated weeks. Older systems that took about 4 weeks have been replaced by newer systems, such as the
disease depend on the predominant site of involvement; systemic BACTEC radiometric system, which speed up the process, thus reducing culturing time by about 2
symptoms include fever, night sweats, anorexia, and weight loss. weeks. Antimicrobial susceptibility testing of initial M. tuberculosis isolates from patients should be
performed to test susceptibility to the primary drugs used for treatment.In some cases, such as HIV
RADIOGRAPHIC PROCEDURES infection, in which atypical findings occur, culture-negative findings do not rule out a diagnosis of
Individual with respiratory symptoms and abnormal chest TB and a clinical diagnosis will be supported by other findings. A newer method of diagnosis, the
radiograph supports an initial suspicion of pulmonary Before HIV Mycobacteria Growth Indicator Tube (MGIT), appears to be a rapid, easy-to-use system with a high
infection became common, most cases of TB were pulmonary. accuracy for detecting mycobacteria directly from clinical specimens. This system uses a
However, with the advent of AIDS, the finding of a normal chest traditional broth medium and a novel fluorescent indicator for the recovery of mycobacteria from
radiograph does not rule out the diagnosis of pulmonary TB. patient specimens. The fluorescence in the MGIT is readily visible without elaborate
Persons with HIV infection and TB may have a chest radiograph that instrumentation, enabling large numbers of cultures to be read quickly. Other newer methods of
shows a classic reactivation pattern, an “atypical” (pleural effusion) diagnosis that appear promising include serologic tests that use enzyme-linked immunosorbent
pattern or evidence of past infection. (ELISA) techniques and gene amplification by the polymerase chain reaction (PCR).

2. DIRECTLY OBSERVED THERAPY MULTIPLE DRUG THERAPY
Directly observed therapy is the practice of a health care provider or other The key to treating active TB disease is multiple drug therapy for a sufficient time to kill the
responsible person observing as the patient ingests and swallows the TB organisms and to prevent development of resistant strains. Most cavitary lesions contain
medications. DOT is the preferred core management strategy for all patients with 10 organisms, and the frequency of mutations that confer resistance to a single drug is
approximately 10-6 for INH and streptomycin, 10-8 for rifampin, and 10-5 for ethambutol.
TB. The purpose of DOT is to ensure adherence to TB therapy. DOT not only
Considering the many organisms involved, patients with active TB disease likely harbor
ensures completion of therapy, but it may also reduce the risk of developing drug organisms with random mutations that confer drug resistance to a given drug. If a single
resistance. By improving these two factors, it also reduces the risk to the drug is given, it would reduce the number of drug-susceptible organisms but leave the
community. DOT can be administered with daily or two- to three-times-per-week drug-resistant organisms to replicate. By using multiple drug therapy, the likelihood of
regimens. It can be administered to patients in the office or clinic setting, or it be encountering organisms with mutations to multiple drugs is reduced.Therefore,
given at the patient's home, school, work, or other mutually agreed on place. monotherapy has no place in the treatment of active TB disease.Multiple drug therapy
Although DOT is recommended for all patients, public health departments may also serves to sterilize the sputum and lesions as quickly as possible.Drugs that have
potent early bactericidal activity more rapidly decrease the infectiousness of the patient
not provide it for cost reasons
and reduce the likelihood of developing resistance within the bacillary population.
CONCLUSION
Unfortunately, TB is not a conquered disease of the past. The resurgence of TB and the rising prevalence of drug resistance worldwide indicate that
the battle is being lost. Several factors have been identified that are contributing to this deteriorating situation. Inadequate implementation of
preventive TB measures delays the diagnosis of TB, which facilitates transmission to others. Other factors include the problems of homelessness,
poverty, substance abuse, and the HIV epidemic. In addition, insufficient funding of TB control programs, lack of accessibility to anti-TB medications,
and counterfeit anti-TB agents in various countries are important issues that require exploration and commitment by government agencies, the
pharmaceutical industry, and health care providers.
Drug therapy continues to be the cornerstone of an effective TB treatment plan, enabling TB to be a curable and preventable disease. Advances in
drug development, including a more effective vaccine, will assist in the elimination of TB. Of equal importance, rapid patient identification and isolation
are necessary components of TB control programs. Various strategies have been developed to ensure effective therapy of TB. DOT will eliminate
patient non-adherence to therapy and can be administered two or three times a week. The overall clinical and social management of patients with TB
and their contacts is the ultimate goal. In this setting, the success of therapy is achievable.
KEY POINTS
TB is a global public health problem
TB is transmitted by aerosolized droplet nuclei
Transmission can be reduced by adequate ventilation and ultraviolet lighting
Close contacts are highly susceptible
Contact investigation is an important component of TB prevention and control
VINOEDH NAIDU RAJA GOPAL, BACHELOR OF PHARMACY (HONS) @ ASIA METROPOLITAN UNIVERSITY, IN COLLABORATION WITH LA TROBE UNIVERSITY, AUSTRALIA