Medicine for Africa - Medical Information Service

UBERCULOSIS

Definition:

Tuberculosis (TB) is an infectious disease that has plagued mankind for at least 10,000 years. In ancient Greece, physicians called the disease ‘phthisis’, meaning ‘to waste away’, thus, describing the classic symptom of tuberculosis, causing the body to become weaker and weaker over time. In the 17th and 18th century, close to 25% of all deaths in Europe were caused by TB. Only when Robert Koch isolated the tubercle bacillus in the year 1882, TB was recognized as an infectious disease.

The causative agent of TB is a small, rod-shaped, slow growing and very resistant bacterium, called Mycobacterium tuberculosis (M. tuberculosis); a major variant type is called Mycobacterium bovis. The latter type and other members of the mycobacteria family usually do not infect healthy adults. 

Typically, TB affects the lungs, as the bacteria are most frequently transmitted from person to person by airborne droplets. It is a very contagious disease that is ‘caught’ when, especially in close ‘quarters’ (such as institutions, schools, theaters, public transportation, etc.), an infected person coughs or sneezes, and thus releases the bacterium into the air. Less often, TB can also infect organs other than the lungs, such as the central nervous system (CNS), bones and joints, as well as the circulatory, lymphatic and genitourinary systems, and even the skin.

Following the introduction of antibiotic treatment after World War II, TB was considered to be almost entirely eradicated in developed countries of Europe and the Americas in the early 198os, when a new, devastating disease surfaced – HIV/AIDS! Patients who had been infected by the human immunodeficiency virus (HIV) became the most prevalent new group of patients infected with TB. These patients expressed a seriously decreased immune system which was not able to fight the bacterium, but, in addition, there also surfaced a new, much more virulent strain of TB bacteria – the result of patients who did not adhere to their six-to-12-to-18-months treatment schedule. The result is that today, TB has returned to be a major health risk again – not only for patients who are immuno-suppressed (such as HIV-positive patients), but also anybody else, who may, for whatever reason, have become more susceptible to less obvious infectious agents, or who lives in an area/location that highly favors the spread of the bacterium.

Thus, TB is again a major cause of infection, disease and death in many areas of the world – in 1995 alone, there were three million deaths worldwide attributed to TB. Although the majority of cases still occur in ‘less developed’ countries, primarily in (Southern) Africa, and certain areas in Asia, and are associated with HIV/AIDS, the threat of a worldwide recurrence caused by today’s ‘jet-set’ tourism is very real. In addition, there is a large community of TB-infected patients who do not express obvious disease symptoms or who are not even sick in any way, yet, they are permanent carriers of the bacterium, caught at some time or another from another infected person.  While these ‘TB time bombs’ are not of any concern as long as these people remain healthy, any chronic disease or cancer could turn these patients into actively TB transmitting individuals. Taking this in connection with the development of new TB strains which have become ever more resistant to existing antibiotic treatment – the grounds for a potential new TB epidemic appear to be ‘in the making’…

Symptoms:

Ordinarily, there are only about 10% of patients who are infected with TB and actually develop the disease. The most frequently occurring first symptoms of an active case of TB may be so ‘normal’ that they are often dismissed as the results of a cold or flu. The affected individual may express the development of easily occurring tiredness, a feeling consistent with fever, or may cough frequently. Very often, these early symptoms may go away by themselves, but in about half the cases, they will return.

Actively infected people who express the disease, will express a more or less serious lung or pleural (the lining of the lung) disease process, and the potential of TB spreading throughout the body via the bloodstream becomes more and more likely. Often, affected patients do not seek the advice of a doctor until they experience pronounced symptoms, such as severe pleurisy (inflammation of the membranes surrounding the lungs, causing a sharp pain in the chest when breathing deeply or coughing) or the spitting up of blood (a rather characteristic symptom for TB which should ALWAYS, if present, be followed up with an examination by a physician). While neither of these symptoms is absolutely diagnostic of TB, they should not be ignored. Other, less typical symptoms include fever, loss of appetite, weight loss and night sweats, among others.

Previously treated patients, and patients who did not adhere to their months-long treatment schedule, may turn into permanent carriers, harboring a latent TB infection which may be under control today, but could erupt any day, especially, if the patient experiences an extraordinary stress event, or becomes severely ill due to another cause, thus making him/her immuno-suppressed and a more ‘attractive’ target for dormant TB bacteria within his/her organism.

Other, non-specific symptoms of an active TB infection may include easy fatigue and unexplained weight loss, night sweats and periods of fever/temperature changes, occasional rapid heart beats, shortness of breath and chest pain will occur occasionally in rare cases. The swelling of lymph nodes in the neck or any other part of the body should be a most important alert sign to the patient, to IMMEDIATEDLY consult a physician. Swollen lymph nodes are certainly not characteristic of TB – but, they are a major alarm signal for an actively developing disease in your body, which certainly deserves the attention of a physician’s evaluation!

 
Diagnosis:

Tuberculosis is a disease that cannot be diagnosed easily. As mentioned previously, the M. tuberculosis bacterium is a slow growing bacterium, thus preventing the diagnosis of the current disease status of any patient.
 
After a thorough physical examination, including the personal disease history of the patient, the first step to diagnose the possibility of an active TB disease consists of two standard exams – a chest X-ray and a skin test. Skin tests such as the so-called Mantoux test, the Tine test of the PPD (= purified protein derivative) test, all consist of the intra-cutaneous injection of a bacterial protein derivative onto your forearm. Results will be read after 48 to 72 hours – a red, more than 1-11/2 inch wide spot that is raised (by more than one millimeter) and hardened in consistency would express a positive exposure to the M. tuberculosis bacterium. However, this test has a number of serious limitations, such as, if you have been immunized with a BCG (Bacillus Calmette-Guérin) injection at any time prior to the skin test, the test could show positive results, even though you are not actively sick. Although, there are a large number of ‘subliminal’ cases, in which you may be the carrier of a ‘non-infectious’ strain, or where you may have experienced a TB-bacterial exposure that caused your body to produce a large enough number of antibodies to make the BCG test appear a ‘positive’ test, yet your body’s own immune system was able to easily fight the disease without your even noticing that you were infected at some time.
                                              
The standard way of diagnosing a potential TB disease consists of, aside from taking an X-ray as described above, taking a series of sputum samples which will be examined microscopically after special staining procedures, and which will be cultured in special agar plates, making it possible to identify the very specific type of mycobacterium with which the patient has been infected.  The latter method is very specific, however, for evaluating a TB culture effectively, it takes a minimum of four to six weeks (because the bacterium is a very slow growing organism – see above). Performing a smear of the patient’s sputum or other pulmonary excretory solutions, and staining it for TB bacteria with a specific stain, called AFB – Acid Fast Bacteria, would be the most specific positive exam for the diagnosis of an active TB, as long as one clearly defined rod-shaped TB bacterium can be identified. However, a negative examination would not exclude the possibility of the presence of an active TB infection – because it is usually very difficult to find and identify one of the rod-shaped bacteria. This is particularly obvious, considering the fact that the TB bacterium causes a body-released defense action, resulting in the development of an often dense granuloma (a tight nodule of macrophages/granulation tissue), which can easily obscure the detection of the tiny TB bacteria. The presence of a granuloma is not specific for TB, because there are a number of other infectious agents and fungi that can cause the development of a granuloma.

Extra pulmonary TB can be diagnosed by taking a biopsy of a suspected granuloma, detected by CT-scan (Computer Tomography scan) or MRI (Magnet Resonance Imaging), and examined under the microscope or grown in a culture, as described above).

Very sophisticated tests have surfaced over the last decade due to the advancement of biotechnology and, include tests such as the Polymerase Chain Reaction (PCR), which is a highly sensitive test that can detect the bacterial DNA, and antibody assays that detect the release of interferon gamma by the body in response to the mycobacteria. While PCR can be so sensitive that false positive results can easily occur, if the test has not been performed in a sterile and appropriate manner, the antibody assays are usually rapid and fairly inexpensive tests, called ‘Quick Dry Tests’. These tests show significant advantages over the weeks-long lasting culture tests or the very tedious, not overly sensitive microscopic evaluation; thus, they have a valuable position in the early and fast diagnosis of TB. While these dry tests can accurately diagnose the ‘TB bacterium infestation’, the test cannot differentiate between an active or a permanent TB infection; also, these tests may show positive results if the patient has received a BCG immunization shot at any time prior to the test. Nevertheless, today’s dry tests are a very simple, easy to perform, fairly cheap and effective way to screen patients for the exposure of a potential TB infection.  The costs for these tests are certainly cheap for developed countries, and should, or hopefully will soon become also affordable for less developed countries – the major breeding ground of new TB cases worldwide (aside of HIV-patient related co-infections).

 
Treatment:

Until the middle of the 20th century, there was no treatment available, and infected patients were usually put in sanitariums, isolation or in quarantine, until they died, or in rare cases, survived the disease on their body’s own defense system. The first antibiotic drug to be effective against TB, called streptomycin, was only introduced in 1946, followed by a second drug in 1952, called isoniazid (INH). Streptomycin belongs to a class of drugs called ‘aminoglycosides’; it stops the growth of the bacterium by damaging the cell membranes and inhibiting its protein synthesis. INH is a bactericidal effect, meaning that it can actually kill the bacterium.  In later years, rifampin, also called rifampycin, another bactericidal drug, and pyrazinamide and ethambutol (both bacteriostatic drugs that inhibited the multiplication of the bacterium) enforced the fight against the TB bacterium successfully. Since all those drugs work differently and in different time intervals, they were usually given as a two or three drug regime, in order to produce the most effective results. In addition, the application of a Vitamin B complex was added, in order to limit potential liver damage, caused especially by INH.   This drug regimen was very effective, when taken as prescribed over a period of usually six to 12 months.

The side effects of TB treatment are usually not very frequent, but can become serious. All TB medications can be highly toxic to the liver (see above) and cause jaundice and hepatitis; rifampin can also cause severe flu-like signs and symptoms, such as fever, chills, muscle pain, nausea and vomiting.

Unfortunately, many patients did not adhere to this treatment regimen, and usually stopped taking the drugs when they felt ‘healthy’ again, or when they experienced unpleasant side effects. This caused the slow development of ‘drug-resistant’ mycobacteria, which first surfaced in the late eighties and early nineties. In combination with the concomitant development of HIV/AIDS, TB made a frighteningly massive resurgence worldwide.

On the other hand, because the early antibiotic drugs worked so well, and the remaining active cases (prior to the mid-eighties) were mostly poor people, the pharmaceutical industry did not see the need for developing new anti-TB drugs. Nowadays, the mycobacterium as differentiated into so-called ‘multi drug resistant’ strains which cannot or barely be treated at this time, due to the absence of effective new antibiotic drugs.

There are two types of drug resistance – primary or acquired. Primary resistance occurs in patients who have never received any previous antimycobacterial treatment. Acquired resistance occurs in patients who have been treated in the past, but did not adhere to the recommended regimen or were incorrectly treated (too short, wrong drug combination).

Today, multidrug-resistant TB, ‘MDR-TB’, means any strain of TB that cannot be treated by the two most powerful TB drugs, isoniazid (INH) and rifampin, and extensive drug-resistant TB, ‘XDR-TB’, consists of a recently developed strain of TB that is resistant to the same treatments that MDR-TB is, and additionally resistant to three or more of the second-line TB drugs. These XDR-TB strains present a serious potential threat to a new outbreak of tuberculosis that could spread worldwide within a relatively short period of time, unless new and more powerful drugs will be developed in the meantime.

 
Prevention:

TB is a very contagious disease and can spread easily and rapidly throughout the body. Thus, and especially in view of the above mentioned surfacing of multi-drug resistant TB strains, nowadays, prevention has become more important than ever.

Some general preventive measures include:

If your skin test has turned positive, but there is no evidence of an active TB infection yet, you may consider a preventive treatment with INH only. Isoniazid taken for about nine months can reduce the risk of developing the disease, but your physician has to also consider your individual risk of developing liver disease. Pregnancy is also a contra-indication for treatment with INH.

The only available vaccine is BCG, which has some benefit, but is not widely used (especially not in the USA). The vaccine is not very effective in adults, but can prevent the disease from spreading outside the lungs in infants. Another disadvantage of the vaccine is that it causes false-positive results in future skin tests.

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DISCLAIMER: The above article is only intended to provide general information regarding this topic. It is not intended and does NOT replace the need to consult a medical or other professional person, if you have or believe to have this disease/disorder. While the article was researched, written and reviewed by medical professionals, and Medicine for Africa, its staff and publisher made every effort to assure accuracy and correctness, it does not claim to be complete, correct or to reflect the very latest stand of medical/scientific knowledge in the disease’s/syndrome’s pathology, diagnostic and/or therapeutic development. Medicine for Africa, its founder, management, staff, writers, reviewers or publishers may NOT be made responsible or legally bound to any information provided above, and cannot be held liable to any conclusions or decisions the reader may draw after reading this article. The reader is explicitly advised to consult a licensed physician and to present his/her specific situation before making any health related decisions.