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Introduction: Gutu, a rural district in Zimbabwe, has been implementing comprehensive HIV care with the support of Medecins Sans Frontieres (MSF) since 2011, decentralizing testing and treatment services to all rural healthcare facilities. We evaluated HIV prevalence, incidence and the cascade of care, in Gutu District five years after MSF began its activities. Methods: A cross-sectional study was implemented between September and December 2016. Using multistage cluster sampling, individuals aged [greater than or equal to]15 years living in the selected households were eligible. Individuals who agreed to participate were interviewed and tested for HIV at home. All participants who tested HIV-positive had their HIV-RNA viral load (VL) measured, regardless of their antiretroviral therapy (ART) status, and those not on ART with HIV-RNA VL [greater than or equal to] 1000 copies/mL had Limiting-Antigen-Avidity EIA Assay for cross-sectional estimation of population-level HIV incidence. Results: Among 5439 eligible adults [greater than or equal to]15 years old, 89.0% of adults were included in the study and accepted an HIV test. The overall prevalence was 13.6% (95%: Confidence Interval (CI) : 12.6 to 14.5). Overall HIV-positive status awareness was 87.4% (95% CI: 84.7 to 89.8), linkage to care 85.5% (95% CI: 82.5 to 88.0) and participants in care 83.8% (95% CI: 80.7 to 86.4). ART coverage among HIV-positive participants was 83.0% (95% CI: 80.0 to 85.7). Overall, 71.6% (95% CI 68.0 to 75.0) of HIV-infected participants had a HIV-RNA VL < 1000 copies/mL. Women achieved higher outcomes than men in the five stages of the cascade of care. Viral Load Suppression (VLS) among participants on ART was 83.2% (95% CI: 79.7 to 86.2) and was not statistically different between women and men (p = 0.98). The overall HIV incidence was estimated at 0.35% (95% CI 0.00 to 0.70) equivalent to 35 new cases/10,000 person-years. Conclusions: Our study provides population-level evidence that achievement of HIV cascade of care coverage overall and among women is feasible in a context with broad access to services and implementation of a decentralized model of care. However, the VLS was relatively low even among participants on ART. Quality care remains the most critical gap in the cascade of care to further reduce mortality and HIV transmission. Keywords: HIV; cascade of care; incidence; prevalence; ART; viral suppression, 1 | INTRODUCTION Zimbabwe faces a generalized HIV epidemic [1]. An estimated 1.2 million Zimbabweans aged 15 to 64 years old live with HIV, representing an HIV prevalence in this [...]

Interleukin (IL)-18, formerly called interferon [Gamma] (IFN-[Gamma])-inducing factor, is biologically and structurally related to IL-1[Beta]. A comparison of gene expression, synthesis, and processing of IL-18 with that of IL-1[Beta] was made in human peripheral blood mononuclear cells (PBMCs) and in human whole blood. Similar to IL-1/[Beta], the precursor for IL-18 requires processing by caspase 1. In PBMCs, mature but not precursor IL-18 induces IFN-[Gamma]; in whole human blood stimulated with endotoxin, inhibition of caspase I reduces IFN-[Gamma] production by an IL-1[Beta]-independent mechanism. Unlike the precursor for IL-1[Beta], precursor for IL-18 was expressed constitutively in PBMCs and in fresh whole blood from healthy human donors. Western blotting of endotoxin-stimulated PBMCs revealed processed IL-1[Beta] in the supernatants via an caspase l-dependent pathway. However, in the same supernatants, only unprocessed precursor IL-18 was found. Unexpectedly, precursor IL-18 was found in freshly obtained PBMCs and constitutive IL-18 gene expression was present in whole blood of healthy donors, whereas constitutive IL-1[Beta] gene expression is absent. Similar to human PBMCs, mouse spleen cells also constitutively contained the preformed precursor for IL-18 and expressed steady-state IL-18 mRNA, but there was no IL-1[Beta] protein and no spontaneous gene expression for IL-1[Beta] in these same preparations. We conclude that although IL-18 and IL-1[Beta] are likely members of the same family, constitutive gene expression, synthesis, and processing are different for the two cytokines.

Abstract Background Host genetics influence the outcome of HCV disease. HCV is also highly mutable and escapes host immunity. HCV genotypes are geographically distributed and HCV subtypes have been shown to have distinct repertoires of HLA-restricted viral epitopes which explains the lack of cross protection across genotypes observed in some studies. Despite this, immune databases and putative epitope vaccines concentrate almost exclusively on HCV genotype 1 class I-epitopes restricted by the HLA-A*02 allele. While both genotype and allele predominate in developed countries, we hypothesise that HCV variation and population genetics will affect the efficacy of proposed epitope vaccines in South Africa. This in silico study investigates HCV viral variability within well-studied epitopes identified in genotype 1 and uses algorithms to predict the immunogenicity of their variants from other less studied genotypes and thus rate the most promising vaccine candidates for the South African population. Six class I- and seven class II- restricted epitope sequences within the core, NS3, NS4B and NS5B regions were compared across the six HCV genotypes using local genotype 5a sequence data together with global data. Common HLA alleles in the South African population are A30:01, A02:01, B58:02, B07:02; DRB1*13:01 and DRB1*03:01. Epitope binding to 13 class I- and 8 class –II alleles were described using web-based prediction servers, Immune Epitope Database, (IEDB) and Propred. Online population coverage tools were used to assess vaccine efficacy. Results Despite the homogeneity of genotype 1 and genotype 5 over the epitopes, there was limited promiscuity to local HLA-alleles.Host differences will make a putative vaccine less effective in South Africa. Of the 6 well-characterized class I- epitopes, only 2 class I- epitopes were promiscuous and 3 of the 7 class-II epitopes were better conserved and promiscuous. By fine tuning the putative vaccine using an optimal cocktail of genotype 1 and 5a epitopes and local HLA data, the coverage was raised from 65.85% to 91.87% in South African Blacks. Conclusion While in vivo and in vitro studies are needed to confirm immunogenic epitopes, in silico HCV epitope vaccine design which takes into account HCV variation and host allele frequency will maximize population coverage in different ethnic groups.

Background: Host genetics influence the outcome of HCV disease. HCV is also highly mutable and escapes host immunity. HCV genotypes are geographically distributed and HCV subtypes have been shown to have distinct repertoires of HLA-restricted viral epitopes which explains the lack of cross protection across genotypes observed in some studies. Despite this, immune databases and putative epitope vaccines concentrate almost exclusively on HCV genotype 1 class I-epitopes restricted by the HLA-A*02 allele. While both genotype and allele predominate in developed countries, we hypothesise that HCV variation and population genetics will affect the efficacy of proposed epitope vaccines in South Africa. This in silico study investigates HCV viral variability within well-studied epitopes identified in genotype 1 and uses algorithms to predict the immunogenicity of their variants from other less studied genotypes and thus rate the most promising vaccine candidates for the South African population. Six class I- and seven class II- restricted epitope sequences within the core, NS3, NS4B and NS5B regions were compared across the six HCV genotypes using local genotype 5a sequence data together with global data. Common HLA alleles in the South African population are A30:01, A02:01, B58:02, B07:02; DRB1*13:01 and DRB1*03:01. Epitope binding to 13 class I- and 8 class -II alleles were described using web-based prediction servers, Immune Epitope Database, (IEDB) and Propred. Online population coverage tools were used to assess vaccine efficacy. Results: Despite the homogeneity of genotype 1 and genotype 5 over the epitopes, there was limited promiscuity to local HLA-alleles.Host differences will make a putative vaccine less effective in South Africa. Of the 6 well-characterized class I- epitopes, only 2 class I- epitopes were promiscuous and 3 of the 7 class-II epitopes were better conserved and promiscuous. By fine tuning the putative vaccine using an optimal cocktail of genotype 1 and 5a epitopes and local HLA data, the coverage was raised from 65.85% to 91.87% in South African Blacks. Conclusion: While in vivo and in vitro studies are needed to confirm immunogenic epitopes, in silico HCV epitope vaccine design which takes into account HCV variation and host allele frequency will maximize population coverage in different ethnic groups. [ABSTRACT FROM AUTHOR]

To determine whether a single injection of recombinant human interleukin-11 (rhIL-11) to human subjects would affect endotoxin-inducible cytokine production, 6 dialysis-dependent patients with renal failure and 4 healthy volunteers were subcutaneously injected with rhIL-11 (50 µg/kg). The circulating concentrations of rhIL-11 remained at a constant level of approximately 12 ng/ml for 0.25—6 h in healthy volunteers but were 2-fold higher in dialysis-dependent patients. Venous blood obtained before and after rhIL-11 was stimulated with 10 ng/ml of LPS for 24 h at 37°C and production of TNFα, IL-1β, and IL-8 determined. The maximum suppression of IL-1β, TNFα and IL-8 production (66%, 24% and 58%, respectively) was observed 1 h after rhIL-11 administration. After 24 h, when circulating concentration of rhIL-11 had decreased to near pre-injection levels, LPS-induced TNFα and IL-1β production remained suppressed (56 ± 17%, P < 0.05; 46 ± 4.7, P<0.01, respectively) but returned to baseline at 48 h. These findings suggest that there is a therapeutic benefit of single doses of rhIL-11 in reducing LPS-induced IL-1β and TNFα production. [ABSTRACT FROM PUBLISHER]