MadSci Network: Microbiology

Re: Tuberculosis

Area: Microbiology
Posted By: Mike Crawford, Graduate Student, Genetics
Date: Wed May 1 12:25:35 1996

Thanks for your question Josh:

The pathology of mycobacteria is due to many factors, but two are most important for dormancy: the slow metabolic rate of the bacteria (doubling time of 24 hours) and the ability of the bacteria to invade cells and replicate within them. The following sequence of events is typical for Mycobacterium tuberculosis infection. The host (let's call him Smiley) inhales tiny water droplets carrying the bacteria which have been coughed up by Smiley's friend who has an active tuberculosis infection. The mycobacteria infect the lung tissue, mainly invading white blood cells such as macrophages and eosinophils, but possibly epithelial cells as well. Smiley has a healthy immune system, and soon the other white blood cells in his lung migrate to the area of infection to begin wiping out the bacteria. But alas! There are no bacteria around to destroy; they are all inside the host cells. The immune cells of Smiley's lung want to keep the infection contained so they form a granuloma: basically a nodule of infected cells in the middle surrounded by fibrous tissue and immune cells such as T-cells and macrophages on the outside. The actual cause of granuloma formation is unknown, but the T-cell cytokine interferon-gamma is necessary. Granulomas show up as opaque nodules in the chest X-rays of patients and allow for diagnosis of tuberculosis infection. Mycobacterium tuberculosis granulomas can be maintained for the lifetime of the individual because the bacteria divide so slowly and eventually enter a state of stasis.

Now lets say Smiley's immune system becomes compromised 20 years later either by co-infection with HIV, malnutrition, or old age. His blood count of T-cells decreases, which leads to a decrease in interferon-gamma production. The exact details of granuloma dissolution are unknown, but eventually the bacteria escape from their encapsulated area and spread throughout the lung tissue. At this time Smiley is contagious, coughing up mucous, blood, and aerosolized water droplets all infected with tuberculosis bacilli. Fortunately for Smiley, his physician recognizes the symptoms and prescribes a regimen of isoniazid and rifampin every day for a year. (Let's assume he doesn't have a drug resistant strain) He follows the doctors orders to the letter, gets over his tuberculosis infection, and leads a long and prosperous life as a "stud calendar" model.

Okay, what if Smiley had contracted a drug-resistant strain? If a strain is resistant to only one or two antibiotics, the prognosis is still fairly good dependent upon two other conditions: the patient completes the antibiotic regimen (often taking 2 or 3 drugs every day for a year) and the patient has a healthy immune system (HIV patients have a decreased cure rate). Unfortunately, strains of tuberculosis bacilli have arisen over the last decade which are resistant to more than one antibiotic, sometimes lots of antibiotics, hence the term multi-drug resistant. This problem was initiated by patients who never finished their course of treatment, selecting for bacteria expressing drug-resistant mutations which then multiplied and spread. Multi-drug resistant tuberculosis is currently a problem in certain areas where overcrowding, lack of adequate health care, and a high incidence of co-infection with HIV have fostered it: inner cities, prisons, third world countries, etc. Most middle class Americans (except for those health care workers who treat patients infected with the bacillus) are probably at low risk, but multi-drug resistant tuberculosis may be the death knell for millions of less privileged people throughout the world in the coming years. Only in the last 5 years have governments and drug companies recognized the global implications of multi-drug resistant tuberculosis, and revived tuberculosis research in an effort to cure this disease.

For more info on the pathogenesis, you may want to check out this site on TB

Sheila Koszycki and Michael Crawford

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