Organisms Causing Pulmonary Infections

Tuberculosis

The mycobacterial infection most commonly associated with AIDS in the tropics is tuberculosis. In the autopsy series of Lucas and colleagues from the Ivory Coast, the most common cause of death in HIV-positive patients was tuberculosis, disseminated in the vast majority of cases. In 32% it was the cause of death, while in an additional 6%, active tuberculosis was present but not the primary cause of death. Fifty-four percent of HIV-positive patients with AIDS-defining pathology had tuberculosis. The disease was disseminated in almost all of these patients and tuberculous meningitis and tuberculous enteritis were common extrapulmonary manifestations.

Even prior to the onset of the AIDS epidemic, tuberculosis was an extremely common cause of morbidity and mortality in the tropics, with a prevalence of infection much greater than 50% (see Chapter 5). In the tropics, it is probable that many people are already infected with M. tuberculosis before becoming HIV positive, but those with HIV have a greatly increased risk of developing or reactivating tuberculosis as compared with seronegative patients. For example, the study by Leroy and colleagues of women in Kigali, Rwanda, demonstrated an 18.2 fold increase in the incidence of active tuberculosis in HIV-positive patients after 4 years of follow-up as compared with HIV-negative controls. As has been confirmed by recent DNA fingerprinting studies, the majority of HIV-associated active tuberculous infections, even those occurring after adequate treatment, are the result of reactivation, although primary infection or reinfection also occurs. HIV-infected tuberculosis patients have a higher incidence of fever, tuberculin skin test anergy, and positive blood cultures than normal hosts.

The interaction between tuberculosis and HIV may have consequences for both epidemics. Cases of tuberculosis have increased twice as fast in countries with high HIV seropositivity as compared to countries with low seropositivity. In very broad terms, about a third of tuberculosis cases can be attributed to HIV. Poor cell-mediated immunity in HIV leads to greater susceptibility to tuberculous infection, and these individuals then transmit the disease to others, further increasing the epidemic. The risk of reactivation of tuberculosis in an AIDS patient over the course of 1 year approximates the risk of reactivation in an HIV-negative patient over a lifetime. The rapid progression to clinical tuberculosis in AIDS patients contributes to the development of resistant strains of tuberculosis. There is increasing evidence that tuberculosis speeds the clinical course of pre-existing HIV infection, and recent studies have suggested that treatment for tuberculosis will actually increase CD4+ cell counts in some AIDS patients.

The prevalence of HIV in patients with tuberculosis in sub-Saharan African countries ranges from 20% to 67%: in Mexico it is about 25%, in Central America and South America about 20%-30%. In Central Africa about 40% of HIV-positive autopsies show disseminated tuberculosis. Of those patients dying with "slim disease," 44% had disseminated tuberculosis at autopsy. Among patients with extrapulmonary tuberculosis, the majority will be HIV-positive. Extrapulmonary tuberculosis has been found in 70% of patients with tuberculosis who have CD4 counts of less than 100 cells/mm³.

As previously noted, the high incidence of tuberculosis can confuse AIDS statistics. Where only clinical criteria are used for the diagnosis of AIDS, there may be overdiagnosis of AIDS in patients who only have tuberculosis. The same clinical findings may be seen in both, such as weight loss exceeding 10% of body weight, with fever and cough for a month or more. Many patients with untreated tuberculosis, particularly those who are undernourished or in chronic ill health from parasites, will meet the clinical criteria for AIDS without actually having the disease. On the other hand, AIDS patients infected with tuberculosis often have no sputum, negative sputum smears, or negative chest radiographs, making the diagnosis of tuberculosis more difficult. Extrapulmonary tuberculosis may produce extensive lymphadenopathy in patients with AIDS, often with low-density or hypoechoic necrotic centers seen on CT or ultrasound scanning. It may be impossible to differentiate between tuberculosis and lymphoma, and both may exist together. Tuberculous lymphadenitis in HIV patients (as well as HIV-related lymphadenitis) tends to be bilateral and symmetrical, involving many nodal groups, while tuberculous lymphadenitis in the normal host is usually asymmetrical, focal, and often cervical. Other extrapulmonary manifestations, such as pleural, pericardial, abdominal, meningeal and miliary spread, are very common in AIDS patients. Unfortunately, they are also common in undernourished and chronically unwell individuals without AIDS.

In one study, HIV-2 infection appeared to be associated with a lower tuberculosis mortality than HIV-1 infection or dual infection. However, in Abidjan, patients infected with HIV-2 and tuberculosis showed wasting, diarrhea, candidiasis, and lymphadenopathy, similar to patients with HIV-1. Among those patients presenting with newly diagnosed tuberculosis, 30% were HIV-1 positive, 4% HIV-2 positive, and 9% positive for both strains. It is worthy of note that 25%-30% of these patients with active tuberculosis were purified protein derivative(PPD)negative.

Tuberculosis, provided it is not drug resistant, can be successfully treated even when the patient has AIDS, although a slow response may be expected in advanced HIV infections and the death rate will be much higher in HIV-positive or AIDS patients. Nevertheless, chemoprophylaxis with isoniazid in Zambia resulted in a ninefold decrease in AIDS-related tuberculosis. Although there was no change in the mortality statistics within this group, it can be expected that there would have been a decrease in new cases amongst contacts.

Tuberculosis remains an enormous public health problem, and not only in the developing world. There are similar epidemics in eastern Europe and increasing numbers of cases throughout the developed world due to immigration, AIDS, and the emergence of resistant strains. It is estimated (1998) that about three million people die of tuberculosis every year, and these figures are probably underestimates.

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