The Re-emergence of Tuberculosis “TB”

Aetiology of the disease

Tuberculosis is caused by 2 bacteria, Mycobacterium tuberculosis “M.tuberculosis” and Mycobacterium bovis “M.bovis”. The disease spreads when infected people cough or sneeze.

Causative agent Mycobacterium tuberculosis; M.bovisMethods of transmission Airborne droplets; unpasteurised milkGlobal distribution WorldwideIncubation period Few weeks or monthsSite of action of the pathogen Primary infection starts in the lungs; secondary

infection starts in the lymph nodesClinical features Racking cough, coughing blood, chest pain, shortage

of breath, fever, sweating, weight lossMethods of diagnoses Microscopic examination of bacteria and chest x-raysAnnual incidents worldwide About 20 millionAnnual mortality About 10 million

(Table 1) shows the main features of tuberculosis (TB)

Tuberculosis in context

It spreads rapidly among people living in overcrowded conditions. M.bovis causes TB in cattle and is spread to humans through meat and milk. It is estimated that there were about 800,000 deaths in the UK between the years 1850 and 1950 as a result TB being transmitted in cattle. However, the majority of people with TB, contract the disease from M.tuberculosis. People with this stain TB experience severe and persistent coughing. Their cells release a hormone-like substance that causes fever and suppresses the appetite; such sufferers lose weight and appear emaciated.

The evidence of the disease in the UK declined before the introduction of vaccination during the 1950’s as a result of the improvements in housing and diet. When antibiotic streptomycin was available in the 1940’s, it hastened the reduction in incidence of TB.

Consequently, as a result of better conditions and treatments by the 1960’s, TB was partially eradicated in the UK. However, TB is now showing resurgence with the number of cases of people infected with the disease rising over the past few years. This may be due to the following factors:

Some strains of TB bacteria are resistant to antibiotics The AIDS pandemic is making vulnerable people more susceptible to TB People with general health problems are also vulnerable to TB Poor housing conditions and rising homelessness in cities of countries The failure of TB control programmes in some countries, such as USA

The spread of TB

TB has attacked many of the poorest and socially disadvantaged because it can spread by air droplets and people who live closely together in large numbers are especially at risk. The disease mainly attacks homeless people and those who live in poor housing conditions. Those individuals who have a low immunity because of malnutrition or being HIV positive are practically susceptible to TB.

About third of the world’s population is infected with M.tuberculosis. In 1995 TB killed more people globally than any other disease. M.tuberculosis is attacked by macrophages in the lungs, but not killed. It is predicted that many millions of people will become infected with TB in the next few years. Without the treatment each person may infect about -15 others every year.

Transmission of the disease is achieved easily and it is known that the bacterium may remain in the lungs or lymphoid tissue for years until the symptoms become evident. TB is an opportunistic infection and can strike people who are HIV positive. TB is now the leading cause of death amongst HIV positive people closely by a TB pandemic. The HIV pandemic has been followed very closely by a TB pandemic. There appear to be very high rates of incidence all across the developing world, including countries of the former Soviet Union, (see figure 1). Very high rates of TB are also found in areas like South Africa and Tanzania. Many cases of TB in the USA may have happened as a result of neglect and poverty especially in parts of New York where the public health system almost collapsed. Social factors including homelessness, neglect of primary health care and urban decay, contributed to the spread of TB.

Treatment of TB

When individuals have the characteristic symptoms of TB, the sputum (mucus and pus) from their lungs is collected for analysis. M.tuberculosis may be readily identified by microscopy. If TB is confirmed suffers must be isolated while they are in the most infectious state.

The treatment involves using several drugs to insure that all bacteria are killed. Otherwise, drug resistant bacteria may arise and continue the infection. The treatment is a long process and therefore it may take as long as 6 months to 1 year.

Multiple drug resistant forms of TB now exist (MDR-TB). In 1995, an HIV unit in London reported an outbreak of TB-resistant bacterium, known as MDR-TB, with a form of M.tuberculosis that was resistant to five of the major drugs used to treat the disease including the drug known as isoniazid, which was successful.

The world health organisation (WHO) promotes a programme to ensure that patients complete their course of drugs. Direct observation treatment, short course (DOTS) involves health workers and responsible family members who make sure those patients take their medicine for 6 to 8 months. The drugs used are usually isoniazid and rifampicin, often in combination with other drugs. This drug treatment cures about 95% of all patients and is more affective that other therapies, which has reduced the spread of MDR (Multiple drug resistant) strains.

Control and Prevention of TB

One possible approach to controlling TB is by contact tracing. This method involves asking the person infected with TB to identify the people they may have put at risk by being in contact with them. The spread of the disease in children is prevented by vaccination. The BCG (Bacillus Calnette-Guerin) is a live vaccination (derived from M.bovis) against TB and is the only available vaccine against this disease. BCG can prevent people getting TB about half the time, although estimates can vary widely. The protection BCG provides becomes less effective with time since vaccination.

An effective strategy for controlling TB is the dual method of milk pasteurisation and the TB-testing of cattle. With this approach, any cattle that are found to test positive for TB are destroyed. These measures have effectively reduced the incidence of TB derived from M.bovis in countries where these controls operate.

Chemotherapy and Antibiotics

Chemotherapy is the use of drugs to treat or cure infections. Effective drugs usually slow selective toxicity, so that they kill the pathogen and not the host cells. There are a wide range of drugs for chemotherapy that are effective for bacterial and fungal infections but few for viral infection.

Some of the drugs for treating tuberculosis are natural products, but others are semisynthetic or entirely synthetic. The natural products are antibiotics, which are chemotherapeutic compounds made by microorganisms. These natural products may themselves be chemically modified to increase their effectiveness. They work by interfering with the growth or metabolism of the bacterium by either:

Disrupting the synthesis of bacterial walls Hindering protein synthesis ( by transcription or translation) Affecting cell membrane functions; or Inhibiting enzyme action

Antibiotics such as penicillin work by hindering the synthesis of the cross links between peptidoglycan polymers in the cell wall. Therefore such drugs are only effective against bacteria that are growing. However, there are many bacteria with enzymes for destroying penicillin and so are resistant to antibiotics. Consequently, antibiotics should be chosen by medical professionals wisely. This is achieved by screening antibiotics against strains of the bacterium that is isolated from sufferer. This method insures that the most effective antibiotic is administered.

There are two types of antibiotics used to treat TB sufferers: broad spectrum and narrow spectrum antibiotics. Broad spectrum antibiotics are effective against a much wider range of bacteria whereas narrow spectrum antibiotics are only effective against relatively few bacteria.