No abstract

Human papillomaviruses (HPVs) co-evolve slowly with the human host and each HPV genotype displays epithelial tropisms. We assessed the evolution of intra HPV genotype variants within samples, and their association to anogenital site, cervical cytology and HIV status. Variability in the L1 gene of 35 HPV genotypes was characterized phylogenetically using maximum likelihood, and portrayed by phenotype. Up to a thousand unique variants were identified within individual samples. In-depth analyses of the most prevalent genotypes, HPV16, HPV18 and HPV52, revealed that the high diversity was dominated by a few abundant variants. This suggests high intra-host mutation rates. Clades of HPV16, HPV18 and HPV52 were associated to anatomical site and HIV co-infection. Particularly, we observed that one HPV16 clade was specific to vaginal cells and one HPV52 clade was specific to anal cells. One major HPV52 clade, present in several samples, was strongly associated with cervical neoplasia. Overall, our data suggest that tissue tropism and HIV immunosuppression are strong shapers of HPV evolution.

Background: Recombinant Salmonella vaccine vectors may potentially be used to induce specific CD4+ T cell responses against foreign viral antigens. Such immune responses are required features of vaccines against pathogens such as human immunodeficiency virus type 1 (HIV-1). The aim of this study was to investigate the induction of systemic HIV-1-specific CD4+ T helper (Th) responses in mice after oral immunization with a live attenuated Salmonella vaccine vector that expressed HIV-1 subtype C Gag. Groups of BALB/c mice were vaccinated orally three times (4 weeks apart) with this recombinant Salmonella. At sacrifice, 28 days after the last immunization, systemic CD4+ Th1 and Th2 cytokine responses were evaluated by enzyme-linked immunospot assay and cytometric bead array. HIV-1 Gag-specific IgG1 and IgG2a humoral responses in the serum were determined by enzyme-linked immunosorbent assay.

HIV and cryptococcal meningitis co-infection is a major public health problem in most developing countries. Cryptococcus neoformans sensu stricto is responsible for the majority of HIV-associated cryptococcosis cases in sub-Saharan Africa. Despite the available information, little is known about cryptococcal population diversity and its association with clinical outcomes in patients with HIV-associated cryptococcal meningitis in sub-Saharan Africa. In a prospective cohort, we investigated the prevalence and clinical outcome of Cryptococcusneoformans sensu stricto meningitis among HIV-infected patients in Harare, Zimbabwe, and compared the genotypic diversity of the isolates with those collected from other parts of Africa. Molecular typing was done using amplified fragment length polymorphism genotyping and microsatellite typing. The majority of patients with HIV-associated Cryptococcusneoformans sensu stricto meningitis in this cohort were males (n=33/55; 60.0 %). The predominant Cryptococcus neoformans sensu stricto genotype among the Zimbabwean isolates was genotype AFLP1/VNI (n=40; 72.7 %), followed by AFLP1A/VNB/VNII (n=8; 14.6 %), and AFLP1B/VNII was the least isolated (n=7; 12.7 %). Most of the isolates were mating-type α (n=51; 92.7 %), and only four (7.3 %) were mating-type a. Overall in-hospital mortality was 55.6 % (n=30), and no difference between infecting genotype and clinical outcome of patient (P=0.73) or CD4+ counts (P=0.79) was observed. Zimbabwean Cryptococcusneoformans sensu stricto genotypes demonstrated a high level of genetic diversity by microsatellite typing, and 51 genotypes within the main molecular types AFLP1/VNI, AFLP1A/VNB/VNII and AFLP1B/VNII were identified. This study demonstrates that Cryptococcusneoformans sensu stricto in Zimbabwe has a high level of genetic diversity when compared to other regional isolates.

Background To design appropriate schistosomiasis control programmes that include women and preschool-aged children (PSAC) it is essential to assess their disease profile and the risk factors predisposing them to infection. This study aimed to determine the prevalence of urogenital schistosomiasis and the risk factors of infection among PSAC and their caregivers in an endemic area of Zimbabwe. Methods A cross-sectional study involving screening for urogenital schistosomiasis infections and treatment of 860 participants [535 children aged ≤ 5 years and 325 caregivers (≥ 15 years)] was carried out in five communities, namely Chihuri, Mupfure, Chakondora, Nduna and Kaziro, in February 2016. Haematuria was recorded for each participant and urine filtration was performed to determine the presence and infection intensity of Schistosoma haematobium . A pre-tested questionnaire was administered to the caregivers seeking knowledge, practices and perceptions regarding schistosomiasis. Data analysis was performed using descriptive statistics and logistic regression. Results Overall 132 (15.4%) of the 860 participants had S. haematobium infections. Among these, 61 (18.7%) of the 325 caregivers and 71 (13.3%) of the 535 children were infected. The infection prevalence was significantly different between caregivers and PSAC ( χ 2 = 4.7040, df = 1, P = 0.030). Children whose caregivers used river water for bathing were more likely to be infected compared to children whose caregivers used protected well water (OR: 2.2, 95% CI: 1.3–3.7). The risks of being infected with schistosomiasis were higher in children whose caregivers were infected compared to children whose caregivers had no infection (AOR: 3.9, 95% CI: 1.7–8.6). In caregivers, those who bathed in river water were at higher risk of schistosomiasis infection compared to those who used water from a protected well (AOR: 3.0, 95% CI: 1.4–6.4). Conclusions According to the World Health Organization guidelines, the observed overall prevalence of urogenital schistosomiasis qualifies this area as a moderate risk area requiring mass chemotherapy once every two years. Water contact practices of caregivers, and their perceptions and knowledge regarding schistosomiasis are risk factors for infection in both themselves and PSAC. Thus, disease control efforts targeting caregivers or PSAC should include health education and provision of alternative clean and safe water sources.