Introduction Multiplathogen home-based self-sampling offers an opportunity to increase access to screening and treatment. Infections include sexually transmitted (HIV, Trichomonas vaginalis (Tv), human papillomavirus [HPV] for cervical precancer detection) and non-sexually transmitted pathogens (Schistosoma haematobium (Sh)) pathogens, in endemic settings with high co-infection prevalence. Chronic infection may lead to disability (female genital schistosomiasis (FGS) and death (cervical cancer). The Zipime-Weka-Schista (Do self-testing sister!) aims to evaluate the validity, acceptability, uptake, impact and cost-effectiveness of multi-pathogen self-sampling for genital infections among women in Zambia. Methods and Analysis This is a longitudinal cohort study aiming to enrol 2,500 non-pregnant, sexually active and non-menstruating women aged 15-50 years from two districts in Zambia with two year follow up. During home visits, community health workers offer HIV and Tv self-testing and cervicovaginal self-swabs for (i) HPV by GeneXpert and, (ii) Sh DNA detection by conventional (PCR) and isothermal (RPA) molecular methods. Schistosoma ova and circulating anodic antigen are detected in urine. At a clinic follow-up midwifes perform same procedures and obtain hand-held colposcopic images. High-risk -HPV positive women are referred for a two-quadrant cervical biopsy according to age and HIV status. A cost-effectiveness analysis is conducted in parallel. Ethics and dissemination The University of Zambia Biomedical Research Ethics Committee (UNZABREC) approved the study in September 2021 (reference: 1858-2021), the London School of Hygiene and Tropical Medicine(LSHTM) (reference: 25258) and Ministry of Health and local superintendents. Written informed consent was obtained from all participants prior to enrolment. Data will be available upon request on LSHTM Data Compass. Identifiable data collected is stored securely and their confidentiality protected in accordance with the Data Protection Act 1998.

The authors have declared no competing interest.

This study is funded through a UKRI Future Leaders Fellowship (MR/T041900/1) awarded to Prof. AL Bustinduy. Prof E Webb and Prof R Hayes received funding from MRC Grant Reference MR/K012126/1. This award is jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and is also part of the EDCTP2 programmme supported by the European Union. Funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The University of Zambia Biomedical Research Ethics Committee (UNZABREC) approved the study in September 2021 (reference: 1858-2021), the London School of Hygiene and Tropical Medicine(LSHTM) (reference: 25258) and Ministry of Health and local superintendents. Written informed consent was obtained from all participants prior to enrolment. Data will be available upon request on LSHTM Data Compass. Identifiable data collected is stored securely and their confidentiality protected in accordance with the Data Protection Act 1998.

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. Data will be available upon request on LSHTM Data Compass. Identifiable data collected is stored securely and their confidentiality protected in accordance with the Data Protection Act 1998.