{"doi":"10.3389/fimmu.2021.620657","title":"Cervicovaginal Immune Activation in Zambian Women With Female Genital Schistosomiasis","abstract":"HIV-1 infection disproportionately affects women in sub-Saharan Africa, where areas of high HIV-1 prevalence and Schistosoma haematobium endemicity largely overlap. Female genital schistosomiasis (FGS), an inflammatory disease caused by S. haematobium egg deposition in the genital tract, has been associated with prevalent HIV-1 infection. Elevated levels of the chemokines MIP-1α (CCL-3), MIP-1β (CCL-4), IP-10 (CXCL-10), and IL-8 (CXCL-8) in cervicovaginal lavage (CVL) have been associated with HIV-1 acquisition. We hypothesize that levels of cervicovaginal cytokines may be raised in FGS and could provide a causal mechanism for the association between FGS and HIV-1. In the cross-sectional BILHIV study, specimens were collected from 603 female participants who were aged 18–31 years, sexually active, not pregnant and participated in the HPTN 071 (PopART) HIV-1 prevention trial in Zambia. Participants self-collected urine, and vaginal and cervical swabs, while CVLs were clinically obtained. Microscopy and Schistosoma circulating anodic antigen (CAA) were performed on urine. Genital samples were examined for parasite-specific DNA by PCR. Women with FGS (n=28), defined as a positive Schistosoma PCR from any genital sample were frequency age-matched with 159 FGS negative (defined as negative Schistosoma PCR, urine CAA, urine microscopy, and colposcopy imaging) women. Participants with probable FGS (n=25) (defined as the presence of either urine CAA or microscopy in combination with one of four clinical findings suggestive of FGS on colposcope-obtained photographs) were also included, for a total sample size of 212. The concentrations of 17 soluble cytokines and chemokines were quantified by a multiplex bead-based immunoassay. There was no difference in the concentrations of cytokines or chemokines between participants with and without FGS. An exploratory analysis of those women with a higher FGS burden, defined by ≥2 genital specimens with detectable Schistosoma DNA (n=15) showed, after adjusting for potential confounders, a higher Th2 (IL-4, IL-5, and IL-13) and pro-inflammatory (IL-15) expression pattern in comparison to FGS negative women, with differences unlikely to be due to chance (p=0.037 for IL-4 and p<0.001 for IL-5 after adjusting for multiple testing). FGS may alter the female genital tract immune environment, but larger studies in areas of varying endemicity are needed to evaluate the association with HIV-1 vulnerability.","journal":"Frontiers in Immunology","year":2021,"id":169884,"datarank":0.5050943744979712,"base_score":3.367295829986474,"endowment":3.367295829986474,"self_citation_contribution":0.5050943744979712,"citation_network_contribution":0.0,"self_endowment_contribution":0.5050943744979712,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":28,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.962,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":454871,"name":"Emily L. 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A. M. Corstjens","orcid":"0000-0002-0004-0526","position":11,"is_corresponding":false},{"id":257498,"name":"Helen Ayles","orcid":"0000-0003-4108-2842","position":12,"is_corresponding":false},{"id":257503,"name":"Richard Hayes","orcid":"0000-0002-1729-9892","position":13,"is_corresponding":false},{"id":701647,"name":"Isaiah Hansingo","orcid":"0000-0003-1022-3788","position":14,"is_corresponding":false},{"id":701648,"name":"Piet Cools","orcid":"0000-0003-2980-5307","position":15,"is_corresponding":false},{"id":499115,"name":"Lisette van Lieshout","orcid":"0000-0001-8170-1172","position":16,"is_corresponding":false},{"id":701649,"name":"Helena Helmby","orcid":"0000-0003-0761-7348","position":17,"is_corresponding":false},{"id":247284,"name":"Grace A. McComsey","orcid":"0000-0003-2690-8888","position":18,"is_corresponding":false},{"id":477217,"name":"Suzanna C. Francis","orcid":"0000-0002-3724-4813","position":19,"is_corresponding":false},{"id":701650,"name":"Amaya L. 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