Evaluation of the World Health Organization staging system for HIV infection and disease in Ethiopia: association between clinical stages and laboratory markers.

OBJECTIVE: To study the association between the clinical axis of the World Health Organization (WHO) staging system of HIV infection and disease and laboratory markers in HIV-infected Ethiopians. DESIGN: Cross-sectional study. METHODS: Clinical manifestations and stage of HIV-positive individuals participating in a cohort study of HIV infection progression, and of HIV-positive patients hospitalized with suspicion of AIDS, were compared to CD4+ T-cell count and viral load. RESULTS: Of the 86 HIV-positive participants of the cohort study, 53 (62%), 16 (19%), 16 (19%), and one (1.2%) were in stage 1, 2, 3 and 4, respectively. Minor weight loss (n = 15) and pulmonary tuberculosis (n = 9) were the most commonly diagnosed conditions among the 38 (44%) symptomatic HIV-positive individuals. Although 23 (27%) HIV-positive participants had CD4+ T-cell counts less than 200 x 10(6)/l, only one was in clinical stage 4. Among 79 hospitalized HIV-positive patients, 15 (19%) and 64 (81%) were in stage 3 and 4, respectively. The majority (83.5%) had CD4+ T-cell counts < 200 x 10(6)/l. Individuals at stage 3 had lower CD4+ T-cell counts and higher viral loads when seen in hospital as compared to cohort participants (P = 0.06 and 0.008, respectively). When grouping the two study populations, the median CD4+ T-cell count decreased (337, 262, 225, 126, and 78 x 10(6)/l, P< 0.01), and the median viral load increased (4.08, 3.89, 4.47, 5.65, and 5.65 log10 copies/ml, P < 0.01), with increasing clinical stage of HIV infection (1, 2, 3 cohort, 3 hospital, and 4, respectively). Median CD4+ T-cell counts were remarkably low in HIV-negative participants (749 x 10(6)/l), and in HIV-positive participants at stage 1 and 2 (337 and 262 x 10(6)/l, respectively). CONCLUSIONS: There was a good correlation between WHO clinical stages and biological markers. CD4+ T-cell counts were low in Ethiopians, particularly during early stages of HIV-1 infection, and preliminary reference values at different stages of HIV-1 infection were determined. In HIV-infected Ethiopians, lymphocyte counts less than 1,000 x 10(6)/l in non-hospitalized individuals, and less than 2,000 x 10(6)/l in hospitalized patients, had high positive predictive value, but low sensitivity, in identifying subjects with low CD4+ T-cell counts (< 200 x 10(6)/l) who would benefit from chemoprophylaxis of opportunistic infections. The on-going longitudinal study will be useful to confirm the prognostic value of the WHO staging system.

Immune reactivity to fractionated Leishmania aethiopica antigens during active human infection.

Fractionated antigen preparations of Leishmania aethiopica parasites were used to stimulate the peripheral blood lymphocytes of patients with active cutaneous leishmaniasis. In assays measuring lymphocyte proliferation, 9 of 10 patients with similar clinical presentations of infection responded in a similar pattern to the fractionated antigens. Marked proliferation was observed in response to antigen fractions with molecular masses of 43 to 36, 33 to 27, and less than 22 kDa. The induction of relatively high levels of gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) was also observed in responses to these same three antigen fractions. In contrast, the proliferative, IFN-gamma, and TNF-alpha responses of patient lymphocytes to antigens with a molecular mass greater than 60 kDa were uniformly low. The results of this study suggest that the antigens of Leishmania parasites, which are recognized by T cells in patients with active cutaneous leishmaniasis, may be partitioned in the lower-molecular-mass antigenic determinants associated with whole-parasite preparations. The observed association between antigen-induced proliferation and IFN-gamma and TNF-alpha production may be indicative of potential disease-limiting immune effector activities which have developed during infection.