Mycobacteria

The genus Mycobacterium is comprised of at least 40 species which are distinguished from other bacteria by their cell walls which contain lipids including mycolic acids(from which the genus derives its name). When stained these lipid rich cell walls resist decolorization with strong acids, a characteristic responsible for the term Acid Fast Bacilli (AFB), which is synonymous with mycobacteria.

Though many species have been described to infect human beings, three species are most important: M. tuberculosis – the causative agent of tuberculosis (TB), M. leprae – the causative agent of leprosy, and the M. avium complex (MAC) – important opportunistic pathogens of AIDS patients.

Mycobacterium tuberculosis

Epidemiology

Tuberculosis is the most prevalent and important bacterial infection of man. It is estimated that 2 billion people are infected worldwide and that greater than 20 million deaths per year are directly attributable to tuberculosis.

Rates of tuberculosis declined steadily during this century in the western industrialized world until 1985 when a sharp upturn in incidence occurred. The increased incidence was mainly due to patients with AIDS developing active TB, a problem of very large importance, particularly in inner city USA. The other factor that has increased the profile of TB as a public health problem is drug resistance. There are now many people infected with strains of TB for which there is no effective antimicrobial therapy.

The intersection of HIV/AIDS with tuberculosis, particularly in sub-Saharan Africa, is one of the most pressing world public health problems.

Not all people infected with TB develop active disease, however viable TB bacilli remain within the infected person for life, their replication kept in check by host immune function. Approximately 10% will develop disease, half within the first year of becoming infected.

Two groups account for most of the cases of active tuberculosis in Canada. Recent immigrants from high-prevalence areas of the world, in particular Asia and Africa account for a growing proportion of cases as immigration levels have increased. Native-Canadians both on reserves and in urban areas have a much higher prevalence of TB than the non-aboriginal population in Canada.

Clinical Disease

Tuberculosis can involve any organ system, though most infection is pulmonary. Infection is initiated by inhalation of “droplet nuclei” tiny TB bacillus containing particles that are suspended in air after a cough by an infectious individual.

Onset of illness is typically insidious with malaise, weight loss, fever, night sweats and cough. A high index of suspicion is necessary as symptoms may be very non-specific. Knowing the epidemiology and likelihood of prior TB infection in the population you are dealing with is essential.

Diagnosis

Tests for immune response
Injection of purified protein derivative (PPD) using an intradermal (Mantoux) technique is useful in determining past infection. A positive test indicates prior infection and stays positive for life but does not define active disease.

Recently, Interferon – gamma release assays have become available and have the advantage of being lab-based blood tests. Blood is mixed with specific TB antigens and if the patient is infected with M. tuberculosis, their white blood cells will release IFN-gamma. They are likely to soon replace the cumbersome Mantoux skin test.

Direct microscopy
Any specimen type can be stained with special stains that employ strong acid decolorization identify organisms as “Acid-Fast bacilli”. Sputum is most commonly evaluated. The most commonly used stains are Ziehl-Neelsen and auramine-O.

Culture
This is the most sensitive practical way of diagnosing active TB. It is performed in specialized laboratories (mostly Provincial Public Health Laboratories in Canada). Mycobacterium tuberculosis grows very slowly therefore several weeks may be necessary before growth is evident and cultures are not considered negative until six weeks have passed.

It is important to culture organisms in order to confirm diagnosis and perform susceptibility testing. Resistance to anti-tuberculosis antibiotics is a very worrisome and growing problem.

Nucleic Acid Amplification techniques
PCR and related tests are becoming increasingly used for the diagnosis of tuberculosis.

Further Reading

Mycobacterium leprae

Leprosy is a disfiguring condition of more than historical interest. The synonym Hansen’s disease may be preferable as it promotes less stigmatization of the affected individual. Approximately 6 million people are infected in Africa, Asia, Latin America and the South Pacific.

Mycobacterium leprae does not grow on artificial media. Diagnosis is based on clinical and histological grounds.

Here is a description of a case used in a recent tropical medicine course. Gorgas Leprosy Case

Mycobacteria Other Than Tuberculosis (MOTT)

The term MOTT is used to describe all of the other species of Mycobacteria that cause human disease. They are also commonly referred to as “Atypical Mycobacteria”. Many different species are occasionally associated with human infection and disease production.

Two types of manifestations dominate. Chronic pulmonary infection resembling tuberculosis and cervical lymphadenitis can be caused by Mycobacterium avium complex, M. kansasii, M. szulgai, M. xenopi, M. scrofulaceum, M. chelonae and M. abscessus among others.

Mycobacterium avium complex (MAC)

The most important MOTT are those referred to as the Mycobacterium avium complex (MAC). The nomenclature for this group of mycobacteria is somewhat confusing. The two species M. avium and M. intracellulare that make up the M. avium complex are very difficult to distinguish from one another and have similar epidemiology. They are also referred to as M. avium-intracellularae or MAI.

While occasionally causing lymphadenitis or pulmonary disease in immunocompetent individuals, MAC has gained importance in recent years as a prominent opportunistic pathogen of AIDS patients. Disease due to these organisms occurs late in the course of HIV infection, generally when CD4 lymphocyte counts are less than 100/mm3 . It is manifest by systemic symptoms such as weight loss, fatigue, fever, night sweats etc. Diagnosis is made by culture of blood or tissue.