This study has demonstrated that preventive therapy with either twice weekly isoniazid for 6 months or a combination of rifampicin and pyrazinamide for 3 months reduced the incidence of TB in HIV-infected persons in Zambia. No effect was observed on mortality. The effect was greatest in persons who had a positive TST or a lymphocyte count of 2x10(9)/l or greater, indicating that preventive therapy may be more effective in people with less advanced immunosuppression. The limited duration of the protective effect reported in this study raises the question of the need for lifelong preventive therapy or re-prophylaxis.

Both PT regimens protect against tuberculosis for at least 2.5 years but appear to have no effect on HIV progression or mortality. These results may be used in cost-effectiveness models of PT.

The adrenal glands were shown to be the most severely infected organs in the early phase of HSV-1 infections (up to 10 days p.i.) after i.p. infections in mice. Virus could be isolated from the adrenal glands as early as one hour after infection with pathogenic and apathogenic strains. Infection of the adrenal glands is a result of viremia. The content of HSV-1 (5 strains) was much higher in the adrenals than in spleen and liver. It peaked at 3-4 days p.i. compared to 1-2 days in spleen and liver. Only strain 17 syn+ produced low tissue titres in the adrenal glands. Morphologic alterations by HSV-1 infections commenced with distinct foci 2 days after infection in the zona fasciculata, detected immunohistochemically by HSV-specific peroxidase-staining. Necrotic cells could be observed. The foci became confluent until day 4 and remained in this status up to day 7 p.i. During infection immunocompetent cells (macrophages, granulocytes, many T-helper--but only few T-cytotoxic/suppressor lymphocytes) could be observed. On day 10 p.i. the viral antigen had been completely eliminated. In contrast, intraperitoneal infections with 5 strains of HSV-2 resulted in infection of the adrenal glands only to a low degree. The titer of virus was low (exception: strain HG 52). This correlates well with the type of disease produced by either HSV-1 or 2. By comparing the replication of different strains of HSV-1 and 2, three types of "tropism" after i.p. infection of mice can be distinguished.

Wasting in African AIDS patients is severe, and its aetiology is probably multifactorial: persistent diarrhoea, poverty and tuberculosis may all contribute. We report a cross-sectional study of body composition measured anthropometrically in 75 adult patients with HIV-related persistent diarrhoea in Lusaka, and its relationship to gastrointestinal infection and systemic immune activation assessed using serum neopterin and soluble tumour necrosis factor receptor (sTNF-R55) concentrations. Patients as a group were generally severely wasted (mean body mass index (BMI) 15.8 kg/m2, range 11-22), but the severity of wasting was related neither to oesophageal candidiasis nor to intestinal infection. In men but not women, all measures of nutritional status were negatively related to serum sTNF-R55 concentration (fat-free mass in men, r = -0.64; 95% CI: -0.80, -0.41; p < 0.0001). Some wasted patients had cutaneous features of malnutrition, again associated with higher sTNF55 concentrations, and two had peripheral oedema. The diarrhoea-wasting syndrome in this part of Africa seems to be associated with evidence of high cytokine activity in men, rather than oesophageal candidiasis or any particular intestinal opportunistic infection. This immune activation requires further investigation in the context of the sex difference we have observed.

Neopterin is a biochemical marker for the activation of the cell-mediated immune system. We measured neopterin, beta 2-microglobulin, and acute phase proteins in 31 HIV-seropositive and -seronegative Zambian patients with tuberculosis, using stored sera that had been obtained at the beginning and at end of antituberculosis treatment. In both HIV-seropositive and -seronegative patients neopterin and acute phase proteins were elevated when tuberculosis was initially diagnosed and fell during treatment. In contrast, the mean beta 2-microglobulin level increased during antituberculous therapy in the HIV-seropositive group. Serum neopterin levels at diagnosis were correlated with other parameters of disease activity (fever, anemia, and weight loss). In both groups, patients with persistently elevated neopterin levels at the end of treatment were more likely to suffer relapse of tuberculosis or other adverse health events in the subsequent follow-up period. Neopterin can be used to monitor the response to antituberculous therapy in both HIV-seropositive and -seronegative patients and may have a prognostic value for the patients' wellbeing in the follow-up period.