KEYWORDS

MYCOBACTERIAL DISEASES

Mycobacterium tuberculosisObligate aerobe acid-fast rodsTUBERCULOSIS OVERVIEW, CAUSE, AND PATHOGENESISTuberculosis, MTB, or TB (short for tubercle bacillus)common, and in many cases lethal infectious diseasecaused by various strains of mycobacteriausually Mycobacterium tuberculosis

Mycobacterium tuberculosis, was identified and described on 24 March 1882 by Robert Koch

Tuberculosis may infect any part of the bodymost commonly occurs in the lungspulmonary tuberculosisTuberculosis holds a special place in medical history

Can humble master clinicianschallenge public health authoritiestreatable and preventable

WHOover 8 million cases2 million deaths occur worldwide each year

25% to 33% of the worlds population with silentlatent infectionwithM. tuberculosisTuberculosis in the United States is now largely a disease of the disadvantaged

In 2006, there were 13,767 reported cases of TB in the United Statescases were reported in every statedrug-resistant casesco-infection withM. tuberculosisand HIVestimated 10 to 15 million persons remain latently infectedMycobacterium tuberculosisslightly curved or straight rod-shaped bacillusrequires special acid-fast stains to be visualized

It is closely related to M. bovisprimarily pathogen of cattle and related animals

M. tuberculosisis also related toM. lepraeleprosytuberculosis, commonly called M. TB or simply the tubercle bacillus, is a slightly curved or straight rod-shaped bacillus (figure 1) that requires special (acid-fast) stains (figure 3) to be visualized by routine microscopy. It is closely related to M. bovis, which, as the name implies, is primarily a pathogen of cattle and related animals. M. tuberculosis is also related to M. leprae, the causative agent of leprosy, as well as to numerous other mycobacterial species, which are referred to collectively as non-tuberculous mycobacteria (NTM, see below). Infections due to NTM are not spread from person to person and thus do not have the same community health importance as cases of tuberculosisTuberculosis is spread from person to personthrough the air by droplet nuclei1 to 5 m in diameter that have been expulsed into the air

Cough is the primary means by which tubercle bacilli are aerosolizedsinging, sneezing, or speaking may contribute to a lesser extent

Droplet nucleismall enough to remain suspended in the air for long time

The probability of transmission depends on numerous factorssource caseexposed contactair space shared

Usual pathogenesis of tuberculosis. About 5% of infected persons develop clinical disease within the first year of infection; another 5% develop reactivation later during their lives.TB pathogenesis begins when a droplet containing viable tubercle bacilli is inhaled

Bacilli then spread through the pulmonary lymphaticsreach lymph nodesmay become enlarged

Efferent lymphatics then carry bacilli into the systemic circulationthe lungs, the brain, kidneys, and bones

Tubercle bacilli replicate relatively slowlydividing time within 18 to 24 hours20 minutes for most common pathogens

Thus, the process of local, lymphatic, and eventual systemic spread described above typically requires several weeksPULMONARY TUBERCULOSISWorldwide, tuberculosis remains the most common cause of death

Pulmonary tuberculosis is the most common manifestation and the form of the disease usually responsible for its transmission

The usual patient with pulmonary tuberculosis presents with a history of several weeks of a progressive illness

The most important pulmonary symptom is cough

Constitutional complaints coexist and may predominatefever, chills, night sweats, weight loss, appetite loss, and easy fatigability

HIV and TBHIV has greatly increasing the risk of TB

Diagnosis of TB in patients with HIV can be difficult

Suspicion of TB is an indication for HIV antibody testingLaboratory diagnosis1- Mantoux skin test (Tuberculin)

2- Chest X-ray

3- Isolation of Mycobacterium speciesLwensteinJensen medium (L.J medium)microscopic positive results for acid-fast bacilli

4- Identification of microbial genetic materialmolecular methods such as PCR

Positive skin test - tuberculosisindicates exposure to organismdoes not indicate active disease

The Mantoux skin test consists of an intradermal injection of one-tenth of a milliliter (ml) of PPD tuberculin.

The size of induration is measured 4872 hours later. Erythema (redness) should not be measured.

Mantoux test injection site in a subject without chronic conditions or in a high-risk group clinically diagnosed as negative at 50 hours

Skin testing for tuberculosis, using the Mantoux test.

Chest X-rayMicroscopic Examination of MycobacteriumThe Mycobacteria are aerobic acid fast, non-motile, non-spore forming rods

M. tuberculosis is a non-spore forming, non capsulated straight or slightly curved rod, measuring 1-4m x 0.2-0.6 m

The most common pathogens that cause disease to man areM. tuberculosis, M. bovis, M. africanum, and M.microti

Laboratory diagnosis M. tuberculosis acid fast bacteria sputum

TB in Sputum

M. tuberculosis is best demonstrated by using the Ziehl -Neelsen technique or a fluorescence technique. When stained by ZN, they appear as thin pink rods arranged singly or in groups.

Once stained, they resist decolorization with 2% H2SO4 and alcohol or 3% HCl in 95% ethyl alcohol (Acid-fast, Alcohol fast).Cultural Characteristics and colony morphologyM. tuberculosis is strict aerobicgrows very slowly (2-4 weeks)egg enriched mediumLowenstein-Jensen mediumgiving dry creamy colored colonies

Other selective media as Middlebrook 7H10, 7H11 agar and 7H9 brothused for primary isolationantibiotic susceptibility testing

M. tuberculosis is a non chromogendoes not grow on media contain p-nitrobenzoic acidthese characteristics help to differentiate them from M. avium, M. intracellulare, and M. kansasiiThe optimum temperature for growth is at 37C

The culture must be incubated up to 12 weeks

M. tuberculosis produces rough, and tough colonies on glycerol and pyruvate egg media

They are niacin producers and grow under aerobic conditions at 37 C

TB Culture

Cultivation and culture characteristics of Tubercle bacilli on Lowenstein Jensen medium (raised dry cream colored colonies) Tuberculosispolymerase chain amplificationrapid diagnosis

Antibotic treatment - tuberculosisextensive time periods (e.g. 9 months)organism grows slowly, or dormanttwo or more antibiotics e.g. rifampin and isoniazidresistance minimized

Tuberculosis and Drug resistanceMultiple drug resistant (MDR)resistant to first line drugs Extremely drug resistant (XDR) Resistant to some of the second line drugsNearly un-treatableTransmission -tuberculosisM. tuberculosis causes diseasehealthy individuals transmitted man-man airborne droplets

Aerosol from SneezeVaccination BCG vaccine an attenuated strain of M. bovis not effective

in US, incidence is low vaccination not practiced immunization interferes with diagnosis

An apparatus (4-5 cm length, with nine short needles) used for BCG vaccination in Japan. Shown with ampoules of BCG and saline.

M. avium- M. intracellulare complex (M. avium) non-AIDS infection almost never AIDS major bacterial opportunist multiple drug-resistance

spread from cattle

infected cattle are culled positive skin test

rarely seen in US M. bovis

M. lepraeleprosymajor disease of third worldrare in US

A 24-year-old man from Norway, infected with leprosy, 1886.

Deformities from leprosy in India