Beyond the barrier: Female Genital Schistosomiasis as a potential risk factor for HIV-1 acquisition

Sturt, Amy S.; Webb, Emily L.; Francis, Suzanna C.; Hayes, Richard; Bustinduy, Amaya L.

doi:10.1016/j.actatropica.2020.105524

Cited by 42 publications

(58 citation statements)

References 80 publications

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“…For the cytokines analyzed by logistic regression (IL-5, IL-13, IL-15, and TNF-α), due to the relatively low number of participants with concentrations above the LLOQ, these cytokines were adjusted for age and STI. Because HIV-1 status and the presence of hemoglobin in CVL are both potentially influenced by FGS ( 2 ), and may also affect CVL cytokine or chemokine concentrations, these variables were considered to be on the causal pathway and were not included in the final multivariable model ( S1 Figure ).…”

Section: Methodsmentioning

confidence: 99%

“…However, the presence of hemoglobin in CVL may serve as a surrogate marker for the presence of systemic and/or menstrual blood in the cervicovaginal environment. HIV-1 status and the presence of hemoglobin in CVL are potentially influenced by FGS ( 2 ), but may also independently affect cytokines and chemokine concentrations. Thus, we performed two sensitivity analyses, one compared participants with FGS with those in the FGS negative group after excluding the participants who were HIV-1 positive from both groups.…”

Section: Methodsmentioning

confidence: 99%

“…HIV-1 infection disproportionately affects women in sub-Saharan Africa ( 1 ), where areas of high HIV-1 prevalence and Schistosoma haematobium endemicity largely overlap ( 2 ). Female genital schistosomiasis (FGS), caused most frequently by S. haematobium egg deposition in the genital tract, has been associated with prevalent HIV-1 infection in cross-sectional studies ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

“…Tissue-entrapped eggs are also associated with clinically visible FGS-associated manifestations in the cervicovaginal mucosa ( 7 ). FGS lesions may breach the intact cervicovaginal immune barrier and are hypothesized to provide an entry point for HIV-1 infection ( 2 , 3 ). However, the underlying mechanism for potential HIV-1 vulnerability in FGS has not been fully characterized and requires further investigation.…”

Section: Introductionmentioning

confidence: 99%

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Cervicovaginal Immune Activation in Zambian Women With Female Genital Schistosomiasis

et al. 2021

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cervicovaginal Immune Activation in Zambian Women With Female Genital Schistosomiasis

et al. 2021

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“…Endemic schistosomiasis, specifically female genital schistosomiasis (FGS) among adolescent girls and young women (AGYW), may be associated with increased risk of HIV acquisition [7][8][9][10] . FGS, which is estimated to affect 20-56 million girls, is predominantly caused by S. haematobium, and rarely by S, mansoni, when parasite eggs are deposited in the cervix and vaginal wall 10 . FGS is associated with mucosal changes in the intra-vaginal [EFK1]epithelium (Figure 1) and infertility if the upper genital tract is involved 11,12 The immunologic changes that occur during schistosomiasis may also increase HIV transmission risk [13][14][15] .…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

Association of schistosomiasis and HIV infections: A systematic review and meta-analysis

Patel

Rose

Kjetland

et al. 2021

International Journal of Infectious Diseases

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Schistosomiasis Control: Present Situation and Perspectives

Graeff-Teixeira,

Pieri

2022

Infectious Tropical Diseases and One Health in Latin America

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Beyond the barrier: Female Genital Schistosomiasis as a potential risk factor for HIV-1 acquisition

Cited by 42 publications

References 80 publications

Cervicovaginal Immune Activation in Zambian Women With Female Genital Schistosomiasis

Cervicovaginal Immune Activation in Zambian Women With Female Genital Schistosomiasis

Association of schistosomiasis and HIV infections: A systematic review and meta-analysis

Schistosomiasis Control: Present Situation and Perspectives

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