Objectives Vaginal dysbiosis and STIs are important drivers of the HIV epidemic and reproductive complications. These conditions remain prevalent, partly because most cases are asymptomatic. We have shown that inflammatory cytokines interleukin (IL)-1α, IL-1β and interferon-γ-induced protein (IP)-10 are biomarkers for detecting asymptomatic STIs and vaginal dysbiosis (bacterial vaginosis (BV) or intermediate microbiota). This study aimed to validate the performance of these biomarkers in African women recruited regardless of symptoms.
Methods IL-1α, IL-1β and IP-10 were measured in menstrual cup secretions, endocervical, lateral vaginal wall and vulvovaginal swabs from 550 women from Pretoria, Soweto and Cape Town, South Africa and Bondo, Kenya using Luminex and ELISA. STIs were assessed by PCR, BV by Nugent scoring and vaginal microbiota by 16S rRNA sequencing.
Results Across four study populations and four types of genital specimens, the performance of IL-1α, IL-1β and IP-10 for identification of women with STIs, BV or intermediate microbiota was consistent. Of the genital samples assessed, biomarkers measured in lateral vaginal wall swabs performed best, correctly classifying 76%(95% CI 70% to 81%) of women according to STI, BV or intermediate microbiota status (sensitivity 77%, specificity 71%) and were more accurate than clinical symptoms (sensitivity 41%, specificity 57%) (p=0.0003). Women incorrectly classified as STI/BV positive using the biomarkers had more abundant dysbiosis-associated bacteria, including Prevotella bivia and Gardnerella sp, detected by 16S rRNA sequencing, but not Nugent scoring. Including vaginal pH with the cytokine biomarkers improved the accuracy of the test (82% (95% CI 75% to 88%) correctly classified), although pH alone had poor specificity (61%).
Conclusions An inexpensive, point-of-care screening test including IL-1α, IL-1β and IP-10 (and potentially pH) could be used in resource-limited settings to identify women with asymptomatic STIs and dysbiosis. These women could then be referred for aetiological testing, followed by specific treatment.
- female genital tract
- sexually transmitted infection
- bacterial vaginosis
- point-of-care test
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LM and SB contributed equally.
Handling editor Jackie A Cassell
Contributors LM conceptualised the study, generated some of the data, analysed the data and wrote the manuscript. SB managed the WISH cohort, generated and analysed some of the data and wrote the manuscript. JD, KL and SA generated and analysed some of the data and contributed to manuscript preparation. SD assisted with the management of the WISH cohort, processed clinical samples, generated some of the data and contributed to manuscript preparation. HG and SZJ assisted with the management of the WISH cohort, processed the clinical samples and contributed to manuscript preparation. ALW, TC and HJ supervised the acquisition and analysis of some of the data and contributed to manuscript preparation. FL analysed the data and contributed to manuscript preparation. LVD and KA managed the FEM-PrEP trial, collected clinical data and contributed to manuscript preparation. LGB, GG and JD managed the clinical sites for the WISH study, collected some of the clinical data and contributed to manuscript preparation. JASP conceptualised the study, managed the WISH cohort, supervised the acquisition and analysis of some of the data and contributed to manuscript preparation.
Funding This work was supported by a Strategic Health Innovation Partnerships (SHIP) grant from the South African Medical Research Council (MRC; http://ship.mrc.ac.za) and grants from the Poliomyelitis Research Foundation (PRF; http://www.prf.ac.za) of South Africa and European and Developing Countries Clinical Trials Partnership (EDCTP; http://www.edctp.org). FEM-PrEP was conducted under two grants funded by the US Agency for International Development (USAID; https://www.usaid.gov): the Contraceptive and Reproductive Health Technologies and Research Utilization Program (GPO-A-00-05- 00022-00) and the Preventive Technologies Agreement (GHO-A-00-09-00016-00). Early support was also provided by the Bill & Melinda Gates Foundation (https://www.gatesfoundation.org). LM was supported by the National Research Foundation (NRF) of South Africa (http://www.nrf.ac.za), the UCT Clinical Infectious Diseases Research Initiative/Wellcome Trust (http://www.cidri.uct.ac.za) and the MRC.
Competing interests JASP and LM, together with the University of Cape Town, have submitted a Patent application for IP-10 and IL-1α/β use for diagnosing an inflammatory condition in the female genital tract likely caused by an STI or BV.
Patient consent Not required.
Ethics approval The University of Witwatersrand (M1307) and the University of Cape Town (267/2013) Human Research Ethics Committees and the FHI 360 Protection of Human Subjects Committee (10015) approved this study.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement The data sets used and/or analysed during this study are available from the corresponding author on reasonable request.