Immune response pattern in recurrent Plasmodium vivax malaria

Abstract\ud \ud Background\ud \ud Plasmodium vivax is the causative agent of human malaria of large geographic distribution, with 35 million cases annually. In Brazil, it is the most prevalent species, being responsible by around 70 % of the malaria cases.\ud \ud \ud Methods\ud A cross-sectional study was performed in Manaus (Amazonas, Brazil), including 36 adult patients with primary malaria, 19 with recurrent malaria, and 20 endemic controls. The ex vivo phenotypic features of circulating leukocyte subsets (CD4+ T-cells, CD8+ T-cells, NK, NKT, B, B1 and Treg cells) as well as the plasmatic cytokine profile (IL-2, IL-4, IL-6, IL-10, TNF and IFN-γ) were assessed, aiming at establishing patterns of immune response characteristic of primary malaria vs recurrent malaria as compared to endemic controls.\ud \ud \ud Results\ud The proportion of subjects with high levels of WBC was reduced in malaria patients as compared to the endemic control. Monocytes were diminished particularly in patients with primary malaria. The proportion of subjects with high levels of all lymphocyte subsets was decreased in all malaria groups, regardless their clinical status. Decreased proportion of subjects with high levels of CD4+ and CD8+ T-cells was found especially in the group of patients with recurrent malaria. Data analysis indicated significant increase in the proportion of the subjects with high plasmatic cytokine levels in both malaria groups, characterizing a typical cytokine storm. Recurrent malaria patients displayed the highest plasmatic IL-10 levels, that correlated directly with the CD4+/CD8+ T-cells ratio and the number of malaria episodes.\ud \ud \ud Conclusion\ud The findings confirm that the infection by the P. vivax causes a decrease in peripheral blood lymphocyte subsets, which is intensified in the cases of “recurrent malaria”. The unbalanced CD4+/CD8+ T-cells ratio, as well as increased IL-10 levels were correlated with the number of recurrent malaria episodes. These results suggest that the gradual remodelling of the immune response is dependent on the repeated exposure to the parasite, which involves a strict control of the immune response mediated by the CD4+/CD8+ T-cell unbalance and exacerbated IL-10 secretion.Financial support was provided by grants from FAPEAM, CNPq and Programa\ud do Instituto Nacional de Ciência e Tecnologia em Vacinas (INCT-Vacina). YOC\ud was awarded with a fellowship from INCT-Vacina/CNPq and AGC with a fellow‑\ud ship from CAPES (PhD students). AM and ATC are level 2 CNPq research fellow.\ud MVGL and OAMF are level 1 CNPq research fellows. CRFM, OAMF and ATC are\ud FAPEAM research fellows (PVS Programme - PECTI-AM/PG#019/2013). JGCdR\ud received postdoctoral fellowship from CAPES (PNPD/CAPES programme). The\ud funders had no role in study design, data collection and analysis, decision to\ud publish, or preparation of the manuscript

HIV progression and predictors of mortality in a community-based cohort of Zambian adults.

This article describes immunological HIV progression, mortality, and its predictors in 974 Zambian adults. During 3138 person-years of follow-up, 281 deaths occurred, and the overall mortality rate was 9.0 per 100 person-years. Thirty-six percent of patients were dead within 5 years of enrollment. The median survival in patients with baseline CD4 count ≥500 cells/mm³ was 5.62 years, with CD4 count between 200 and 499 cells/mm³ 5.46 years, and with CD4 count <200 cells/mm³ 3.89 years. The mortality rate increased significantly with older age (6.9 in patients <25 years, 9.3 in individuals aged 25-39 years, 10.2 in patients ≥40 years) and was higher in women (rate ratio 1.29). The median annual change of progression markers was -29.6 cells/mm³ for CD4 count, -3.0% for CD4 count percentage, 1.2 nmol/L for neopterin, -1.9 g/L for hemoglobin, and -70 cells/mm³ for total lymphocyte count. Hemoglobin and neopterin were as accurate as CD4 count to predict mortality

Community study of the relative impact of HIV-1 and HIV-2 on intrathoracic tuberculosis

Background: HIV-1 infection is associated with an increased incidence of and mortality from tuberculosis. Few community studies have examined the effect of HIV-2 on tuberculosis. Methods: We investigated the association between HIV-1, HIV-2 and active tuberculosis in four districts (population 42 709) in Bissau, capital of Guinea-Bissau, with the highest known seroprevalence of HIV-2 infection in the world. From May 1996 to June 1998, tuberculosis surveillance and active case finding among contacts was conducted. Patients were HIV-tested, given specific tuberculosis treatment for 8 months and followed regarding mortality. Simultaneously, an HIV sero-survey was performed in a random sample of 1748 permanent residents. Results: During a 25-month period, 366 tuberculosis cases were identified. After excluding cases among visitors to the area, and adjusting for age, the incidence of tuberculosis was 18.3 times higher (95% CI 12.9-26.0) among HIV-1-positive individuals, 13.7 times higher (9.0-20.7) among dually infected (HIV-1 and HIV-2), and 3.0 times higher (2.1-4.3) among HIV-2-infected compared with HIV-negative individuals. HIV-1 and dually infected tuberculosis patients had a higher mortality rate than HIV-negative tuberculosis patients [mortality ratio (MR) 2.68; CI 1.11 -6.48 and 2.89; CI 1.13-7.39, respectively]. The survival of HIV-2-positive tuberculosis patients was similar to that of HIV-negative tuberculosis patients (MR 1.19; CI 0.46-3.06). Conclusion: The presence of HIV-2 infection increases the incidence of tuberculosis compared with that in non-HIV-infected individuals, but does not affect tuberculosis-related mortality in the short term. In contrast, the presence of HIV-1 infection, alone or with HIV-2, has a several-fold greater impact on both the incidence of and mortality from tuberculosis. (C) 2002 Lippincott Williams Wilkins