Myco. Tuberculosis (Murray 3rd Ed pp 321)

This is a gram +-ve acid fast bacilli. It grows slowly in Lowenstein-Jensen medium (2-8 weeks) and main disease caused is tuberculosis. In most patients, the disease is asymptomatic (as will be discussed later below). 90% of cause is due to inhaled air droplets involving the lungs. There are 3 main strains: 2 human and 1 bovine. Mycobact TB and Mycobact africanum (human): both form niacin under culture, and reduce nitrate whereas Mycobact bovis (bovine): does not form niacin, does not reduce nitrate. Both varieties are intracellular in host, therefore antibody mediated immunity is rather useless.

Pathogenicity and Immunity

Inhalation of aerosolised infectious particles ≫ travel to terminal airways ≫ penetrate into unactivated macrophages located in the alveoli and replicate freely ≫ infected cells destroyed eventually by build up of bacteria≫ cell lysis ≫ new cycle begins of unactivated infected phagocytic cells ≫ meanwhile, circulating macrophages and lymphocytes brought to infectious foci (i.e.: chemotactic factors etc) ≫ formation of a multinucleated giant cells made up of fused macrophages ≫ meanwhile, already infected macrophages can now spread into the blood stream and into other organs (i.e.: spleen, kidney, CNS etc).

Intracellular replication of bacteria leads to CD4+ and CD8+ cells to be activated  CD4+ cells lead to antibody production ≫ due to intracellular nature, this is proved useless ≫ CD4+ release cytokines which activate macrophages ≫ these engulf and kill mycobacteria ≫ cytotoxic T cells lyse macrophages, release mycobacteria therefore now out in the open to be phagocytosed by other activated macrophages≫ if mycobacteria numbers are large then will cause tissue damage due to immune response (i.e.: cytokine toxicity, activation of complement cascade, ischaemia, hydrolytic enzymes derived from macrophages and cell lysis etc).

Collections of activated macrophages trying to control the mycobacterium can be seen histologically as: granulomas. These cells form a wall, preventing spread of bacilli. Larger granulomas become encapsulated with fibrin therefore – protecting bacilli from phagocytosis. This way the bacilli can remain dormant for years only to be reactivated at a later stage, when the person’s immune response is suppressed due to the age related factors, or immunosuppressive condition/therapy.

Clinical Picture

Route of infection: mainly via respiratory tract, can be via gut or skin.

Primary TB: Mostly via respiratory tract, survives intracellularly, healing, fibrosis. From lung can go to lymph nodes, spread systemically. Cell mediated immune response (as documented above) forms granulomas – prevents spread of infection, but if suppressed then can lead to uninhibited spreading and/or eventual death. Some possible conditions:

• bronchopneumonia, septicaemia, infections of spleen, GIT, UGT, bones, skin, miliary tuberculosis

• remains dormant for some years in some cases, only to be reactivated later in life.

Secondary infection:

This can be described simply as reinfection or reactivation of the primary dormant infection.

Diagnosis (Murray 3^rd Ed pp 326)

The clinical signs and symptoms of tuberculosis is representative of the site of infection. Onset of disease is insidious, malaise, weight loss, cough (blood in sputum), and night sweats. Radiographic evidence, positive skin test, and positive culture tests are all used in determining the diagnosis of TB. In miliary TB, positive pulmonary disease may not be present.

For laboratory cultures, you must isolate the bacilli from sputum, pus, urine, CSF etc. Skin tests are used most commonly inoculated with M TB. This gives an idea whether the person is infected, has had previous exposure.

Treatment (Murray 3^rd Ed pp 328)

Slow growing mycobacteria are resistant to most antibiotics, therefore treatment is achieved only my giving multidrug therapy over an extended period of time – to avoid development of drug resistant TB. Frontline drugs include: INH (isoniazid), rifampin, pyrazinamide for 2 months. Additional four months of therapy with INH and rifampin alone. If patient is from a drug resistant area, then you can add ethambutol and streptomycin to the frontline drugs.

Control (Murray 3^rd Ed pp 329)

TB is a highly infectious disease, so developing contacts and tracing cases is essential to maintain a infection free area. Animal sources must be treated, or eradicated – and milk must be pasteurised to avoid Mycobact. Bovis. Vaccination using Mycobact Bovis is commonly used in countries where TB is endemic. Unfortunately BCG cannot be used in immunocompromised patients. Also, another problem is that positive skin reactivity test results in all patients immunised with BCG, therefore proving quite useless as one of the testing methods. The efficacy of immunisation is about 50-80% in children, decreasing with age.

Category: Microbiology Notes