A STATEMENT by the US surgeon general in 1969 that it was time to "close the book on infectious diseases", seems incredible today in the face of figures that prove such diseases remain the largest cause of death in the world, and of them, tuberculosis (TB) is still the leader. Worse yet, TB is on the increase and it provides a global challenge just as acute as AIDS.
Estimates are that one-third of the world's population harbours Mycobacterium tuberculosis and risks developing TB. It is the cause of 6.7 per cent of all deaths in the developing world and 18.5 per cent of all adult deaths. The risk of infection is highest in sub-Saharan Africa -- upto 2 per cent of the population gets infected annually.
The disease is concentrated among young adults in the developing world and even in the US, after a century of decline, TB has increased by 18 per cent since 1985. The active transmission of TB in America has been spilling out of high-risk groups into the general population. The number of cases in US-born children under the age of 5 has increased 34 per cent from 1987 to 1990. According to the latest study covering the period 1986-90, the proportion of total cases in foreign-born individuals in the US has increased from 22.8 to 24.8 per cent, although the largest share of the cases is among US-born individuals.
Researchers attribute the resurgence of TB to several factors, including changing urban social structures, burgeoning high-risk groups, such as the homeless, immigrants and IV drug users, spread of the HIV virus, and outdated public treatment programmes. Compounding the problem is the ominous emergence of drug-resistant TB strains.
Tuberculosis is a sentinel disease in AIDS patients because it is often the first indication of HIV infection. While much of the increase in TB is because of TB and HIV co-infection and, therefore, unavoidable, the rapid course of TB in HIV-seropositive individuals has firmly established immunity plays a major role in restricting TB infection. The precise nature of protective immunity is not yet known and a more thorough understanding of the interaction between TB and AIDS is needed. However, the parallel and symbiotic epidemic of AIDS and TB has given rise to such questions as "Will effective TB control programmes necessitate mandatory HIV screening?" and "Will efforts to protect those with HIV infection from TB require the adoption of restrictive employment practices?" A recent article in Science (Vol 257, No 5073) argues that the increased, active transmission of TB is an indicator of the failure of control programmes to detect promptly and apply effective treatment.
Until five years ago, little beyond the size of its genome and its DNA content was known about M.tuberculosis, but since then, the development of shuttle vectors especially has made it possible to create multivalent, recombinant BCG vaccines, capable of simultaneous immunisation against multiple, protective antigens of several different infectious pathogens. When multiple isolates from different patients exhibit the same DNA fingerprint pattern, a common source is suggested. This molecular epidemiology can be used to track infection sources and the transmission of individual strains, including those that are drug-resistant.
It is disquieting, however, that the current methodology for assessing patterns of antibiotic resistance and susceptibility of strains of M.tuberculosis requires upto 3-12 weeks for completion. Therefore, effective treatment is compromised, as patients do not always comply with prolonged drug regimens. Many patients drop out of chemotherapy in a few weeks, once the debilitating symptoms wane, which creates ideal circumstances for drug-resistant organisms.
The microbial isoniazid and rifampicin are the most effective drugs and resistance to these is a serious public health problem. The case fatality rate of multi-drug-resistant TB may be as high as 40 to 60 per cent. Though scientists are still ignorant of the molecular basis of virulence and pathogenesis, they expect to know within five years, the entire DNA sequence of the M.tuberculosis pathogen. Drug resistance will till then heighten transmission potential, and it is expected that in a worst case scenario, total TB cases may rise at the same rate as in the period 1986-91, which would mean an excess of 86,000 cases in the US that would be a result of active transmission before the end of the decade.
Meanwhile, the global threat of TB has prompted the World Bank to make large loans to Bangladesh and China for their TB control programmes and the International Union Against Tuberculosis and Lung Diseases has established anti-TB projects in seven developing countries, including Tanzania, Mozambique and Nicaragua, and notched an 80 per cent cure rate.