HIV infection and TB

14 HIV infection and TB Kevin M. De Cock & Mark S. Dworkin Four levels of interaction can be identified between HIV infection and tuberculosis, and these have implications for the epidemiology, clinical manifestations, treatment and prevention of both diseases. World Health • 51st Year, No. 6, November-December 1998 j/ 1 I / ) The word synergy is derived from the Greek word synergos, which means working together. Synergism has been defined as "the interaction of discrete conditions such that the total effect is greater than the sum of individual effects." This type of interaction accurately describes the relationship between tuberculosis (TB) and infection with the human immunodeficiency virus (HIV). Both infections are long-term and both may remain silent for long periods. In India, a TB patient has his chest X.rayed to see if there is an improvement in his condition . Each year, 8 million cases of active tuberculosis are recorded throughout the world. Tuberculosis infection is acquired by inhalation of Mycobacterium tuberculosis, a highly infectious organism which is transmitted as an aerosol when a person with pul- monary TB disease coughs; in devel- oping countries more than half the population may be infected with M. tuberculosis. The ability of the human immune system to contain latent TB infection results in only about 10% of infected persons devel- oping active TB at some point in their lives; nevertheless TB still caused about one-quarter of the preventable adult deaths in develop- ing countries before the HIV I AIDS pandemic. The introduction of effective therapy for TB in the 1950s led to optimism about the prospects for global TB control, but some eight million cases of active TB and three million deaths continue to occur annually. HIV infection greatly increases susceptibility to TB, and this has led Photo Panos Pictures IN Cooper© to a tremendous increase of TB in areas where both infections are prevalent. Around 15 million per- sons worldwide are infected with both HIV and M. tuberculosis, of whom over two-thirds reside in sub- Saharan Africa. By the year 2000, some 1.4 million cases, or 14% of the global total, will be associated with HIV infection. Several African countries have seen their TB case- load double or treble since the HIV I AIDS pandemic began. The synergistic relationship between HIV and M. tuberculosis has taken the world from a position of optimism about TB elimination to one of crisis, especially in sub- Saharan Africa, but also in Latin America, the Caribbean, and South and South-East Asia. HIV- associated TB has also increased in the industrialized world, especially in southern Europe and the United States, but the public health infra- structure there has been able to contain the problem. A further hazard has been the emergence of multidrug-resistant TB, that is, dis- ease caused by strains resistant to rifampicin and isoniazid, the most potent anti-tuberculous drugs avail- able. This has disproportionately affected HIV-infected persons in some industrialized countries, and would be disastrous if it took hold in developing countries. Interactions Four levels of interaction can be considered; (i) the effect of HIV on latent TB infection; (ii) primary TB infection in HIV-infected persons; (iii) re-infection with M. tuberculo- sis in HIV-infected persons; and (iv) the effect of TB on the natural history of HIV infection itself. These interactions have implications for HIV and TB epidemiology, clinical manifestations, treatment and prevention. HIV-infected persons with latent TB infection have an annual risk of developing active TB disease that may be as high as 5-10%, the risk being higher the more advanced the stage of immune deficiency. HIV- infected persons are also at risk of progressive disease immediately after infection with M. tuberculosis, and are vulnerable to reinfection. Finally, active TB may adversely affect the clinical course of HIV disease itself. World Health • SlstYeor, No. 6, November-December 1998 IS provide such treatment in many developing country settings. BCG vaccination reduces the risk of disseminated tuberculosis in chil- dren, but contributes little more to overall TB control. Finally, infec- tion control measures such as sepa- rating patients with active TB for the first two weeks of treatment from others, especially HIV-infected persons, should be attempted. With confirmed tuberculosis, this woman wonders what the future holds for her. Photo Panos Pictures/! Toy/or© Despite adequate measures to treat TB, HIV-infected persons are likely to develop other complica- tions, and will require HIV testing and counselling, personal and family support, and further medical care. The HIV pandemic has had a dramatic effect on the epidemiology of TB, especially in sub-Saharan Africa and parts of Asia. DOTS currently offers the best chance of limiting the damage and preventing drug resistance, but still further efforts will be required in areas of high HIV prevalence where TB continues to increase. There is an urgent need for greater investment in TB control and new tools, specifi- cally an effective vaccine, better diagnostics and better drugs. • TB is the commonest opportunis- tic infection that complicates HIV infection in much of the developing world, and is responsible for one- third or more of HIV-associated deaths in sub-Saharan Africa. Clinically, HIV-infected persons with TB mostly show symptoms similar to those of HIV-negative persons, such as fever, cough and weight loss. The diagnostic and therapeutic approach to TB is the same whether people are HIV-positive or HIV- negative. National programme guidelines should dictate the exact regimens used, but certain principles apply internationally. Treatment is initiated with standard regimens of three or four drugs, including ri- fampicin and isoniazid, for an initial intensive phase of two months, followed by a continuation of four to six months of treatment with two drugs. Side-effects to medications are more common in HIV-infected persons, the most severe and com- mon being associated with thioaceta- zone, which should not be used in those infected with HIV. Prevention and control WHO has proposed the DOTS (di- rectly observed treatment, short course) strategy for global TB con- trol. The key elements are govern- ment commitment, sputum smear microscopy to detect infectious cases, standardized short-course treatment, a secure supply of drugs, and a recording and reporting sys- tem. This should be considered the minimum strategy to reduce trans- mission of TB and prevent the emer- gence of drug resistance. To prevent the synergistic rela- tionship between HIV and M. tuber- culosis, both infections need to be prevented, so HIV I AIDS and TB programmes need to collaborate more closely. Early recognition and treatment of persons with active TB are critically important to prevent further TB transmission. Treatment of HIV-infected persons without active TB for six to twelve months with isoniazid reduces their inci- dence of TB in the short term by two- thirds. Unfortunately, it is difficult to Or Kevin M. De Cock is Director, Division of HIV /AIDS Prevention-Surveillance & Epidemiology, Centers for Disease Control and Prevention, 1600 Clifton Road NE Mailstop 0-21, Atlanta, GA 30333, USA, and Or Mark S. Dworkin is a Medical Officer in the same Division. TB patients collecting their drugs from the hospital in China. They will follow their course of treatment under the direct supervision of a health worker. Photo WHO/). Mullins