The WHO atlas for female-genital schistosomiasis: Co-design of a practicable diagnostic guide, digital support and training.

Up to 56 million young and adult women of African origin suffer from Female Genital Schistosomiasis (FGS). The transmission of schistosomiasis happens through contact with schistosomiasis infested fresh water in rivers and lakes. The transmission vector is the snail that releases immature worms capable of penetrating the human skin. The worm then matures and mates in the blood vessels and deposits its eggs in tissues, causing urogenital disease. There is currently no gold standard for FGS diagnosis. Reliable diagnostics are challenging due to the lack of appropriate instruments and clinical skills. The World Health Organisation (WHO) recommends "screen-and-treat" cervical cancer management, by means of visual inspection of characteristic lesions on the cervix and point-of-care treatment as per the findings. FGS may be mistaken for cervical cancer or sexually transmitted diseases. Misdiagnosis may lead to the wrong treatment, increased risk of exposure to other infectious diseases (human immunodeficiency virus and human papilloma virus), infertility and stigmatisation. The necessary clinical knowledge is only available to a few experts in the world. For an appropriate diagnosis, this knowledge needs to be transferred to health professionals who have minimal or non-existing laboratory support. Co-design workshops were held with stakeholders (WHO representative, national health authority, FGS experts and researchers, gynaecologists, nurses, medical doctors, public health experts, technical experts, and members of the public) to make prototypes for the WHO Pocket Atlas for FGS, a mobile diagnostic support tool and an e-learning tool for health professionals. The dissemination targeted health facilities, including remote areas across the 51 anglophone, francophone and lusophone African countries. Outcomes were endorsed by the WHO and comprise a practical diagnostic guide for FGS in low-resource environments.

Female genital schistosomiasis, human papilloma virus infection, and cervical cancer in rural Madagascar: a cross sectional study.

BACKGROUND: Women's health in resource-limited settings can benefit from the integrated management of high-burden diseases, such as female genital schistosomiasis (FGS) and human papilloma virus (HPV)-related cervical cancer. In schistosomiasis-endemic countries such as Madagascar, data on FGS and HPV prevalence are lacking as well as preventive measures for both conditions. This study aims to estimate the prevalence of FGS and HPV in rural Madagascar, and to examine associated risk factors to identify opportunities for improving women's health. METHODS: After initial community outreach activities, interested women aged 18-49 years were recruited consecutively in 2021 at three primary health care centers in the district of Marovoay. FGS was detected by colposcopy. Colposcopy images were double-blind reviewed by two independent specialists. A Luminex bead-based assay was performed on cervical vaginal lavage specimens for HPV typing. Crude (CPR) and adjusted prevalence ratios (APR) of associations between selected factors and FGS and HPV positivity were estimated using univariable and multivariable binary Poisson regression with 95% confidence intervals (CIs). RESULTS: Among 500 women enrolled, 302 had complete information on FGS and HPV diagnosis, and were thus eligible for analysis. Within the sample, 189 (62.6%, 95% CI: 56.9-68.1) cases of FGS were detected. A total of 129 women (42.7%, 95% CI: 37.1-48.5) tested positive for HPV. In total, 80 women (26.5%, 95% CI: 21.6-31.8]) tested positive for both conditions. No association was observed between FGS and HPV positivity, while previous pregnancy (APR = 0.65, 95% CI: 0.43-0.78) and older age (APR = 0.59, 95% CI: 0.42-0.81) are showing a negative association with HPV infection compared to no previous pregnancy and younger age groups. CONCLUSIONS: The results of the study show that FGS and HPV are highly prevalent in rural Madagascar. The concurrent prevalence of these two conditions requires urgent adaptations of public health strategies to improve women's health, such as integrated services at primary level of care.

Knowledge, experiences, and practices of women affected by female genital schistosomiasis in rural Madagascar: A qualitative study on disease perception, health impairment and social impact.

BACKGROUND: Female genital schistosomiasis (FGS) is a neglected manifestation of urogenital schistosomiasis caused by S. haematobium. The disease presents with symptoms such as pelvic pain, vaginal discharge and bleeding and menstruation disorders, and might lead to infertility and pregnancy complications. The perspectives of women with FGS have not been studied systematically. The aim of the study was to understand knowledge, experiences, and practices of women with FGS. METHODS: We performed a qualitative study with seventy-six women diagnosed of having FGS, in the Ambanja district in Northwest Madagascar. Data collection was either through focus group discussion (N = 60) or in an individual semi-structured interview (N = 16). FGS was diagnosed by colposcopy. The data was analysed using Mayring´s qualitative content analysis. RESULTS: Knowledge on how the disease is acquired varied and ideas on prevention remained vague. Patients suffered from vaginal discharge and pelvic complaints. Some women expressed unbearable pain during sexual intercourse and compared their pain to an open wound being touched. FGS considerably impaired women´s daily activities and their quality of life. Infertility led to resignation and despair, conflicts with the partner and to social exclusion from the community. Women fearing to sexually transmit FGS refrained from partnership and sexual relations. Many women with FGS reported stigmatisation. A coping strategy was to share strain with other women having similar complaints. However, concealing FGS was a common behaviour which led to social isolation and delayed health care seeking. CONCLUSIONS: Our study underlines that FGS has an important impact on the sexual health of women and on their social life in the community. Our results highlight the importance of providing adequate health education and structural interventions, such as the supply of water and the provision of sanitation measures. Further, correct diagnosis and treatment of FGS in adolescent girls and women should be available in all S. haematobium-endemic areas. TRIAL REGISTRATION: The qualitative study was embedded in a randomised controlled trial (RCT) in which two doses of praziquantel were compared (https://clinicaltrials.gov/ct2/show/NCT04115072).

Cervical lesion proportion measure using a digital gridded imaging technique to assess cervical pathology in women with genital schistosomiasis.

Female genital schistosomiasis (FGS) is characterized by a pattern of lesions which manifest at the cervix and the vagina, such as homogeneous and grainy sandy patches, rubbery papules in addition to neovascularization. A tool for quantification of the lesions is needed to improve FGS research and control programs. Hitherto, no tools are available to quantify clinical pathology at the cervix in a standardized and reproducible manner. This study aimed to develop and validate a cervical lesion proportion (CLP) measure for quantification of cervical pathology in FGS. A digital imaging technique was applied in which a grid containing 424 identical squares was positioned on high resolution digital images from the cervix of 70 women with FGS. CLP was measured for each image by observers counting the total number of squares containing at least one type of FGS associated lesion. For assessment of inter- and intra-observer reliability, three different observers measured CLP independently. In addition, a rubbery papule count (RPC) was determined in a similar manner. The intraclass correlation coefficient was 0.94 (excellent) for the CLP inter-rater reliability and 0.90 (good) for intra-rater reliability and the coefficients for the RPC were 0.88 and 0.80 (good), respectively. The CLP facilitated a reliable and reproducible quantification of FGS associated lesions of the cervix. In the future, grading of cervical pathology by CLP may provide insight into the natural course of schistosome egg-induced pathology of the cervix and may have a role in assessing praziquantel treatment efficacy against FGS. Trial Registration: ClinicalTrials.gov, trial number NCT04115072; trial URL https://clinicaltrials.gov/ct2/show/NCT04115072?term=Female+genital+schistosomiasis+AND+Madagascar&draw=2&rank=1.

Gynecological manifestations, histopathological findings, and schistosoma-specific polymerase chain reaction results among women with Schistosoma haematobium infection: a cross-sectional study in Madagascar.

BACKGROUND: The pathophysiology of female genital schistosomiasis (FGS) is only partially understood. This study aims to describe the histopathological findings, polymerase chain reaction (PCR) results, and gynecological manifestations of FGS in women with different intensities of Schistosoma haematobium infection. METHODS: Women aged 15-35 years living in an S. haematobium-endemic area in Madagascar underwent pelvic and colposcopic examinations. Small biopsy specimens were obtained from lesions and examined histopathologically. Schistosoma PCR was done on urine, biopsy, cervicovaginal lavage, and genital mucosal surface specimens. RESULTS: Sandy patches and rubbery papules were found in 41 of 118 women (35%). Rubbery papules reflected an intense cellular immune reaction dominated by eosinophils, epithelial erosion, and viable ova. There was a significant decrease in the prevalence of rubbery papules with age, even after adjustment for urinary ova excretion. The sandy patches with grains showed moderate cellular immune reaction and ova (viable and/or calcified). They were most prevalent in cases with low-intensity urinary S. haematobium infection. Forty-two percent of women with Schistosoma-negative urine specimens had at least 1 genital specimen test positive for Schistosoma by PCR. CONCLUSIONS: The results indicate a diversity of lesions caused by S. haematobium and a dynamic evolution of the genital lesions. Schistosoma PCR may give an indication of the diagnosis.

The colposcopic atlas of schistosomiasis in the lower female genital tract based on studies in Malawi, Zimbabwe, Madagascar and South Africa.

BACKGROUND: Schistosoma (S.) haematobium is a neglected tropical disease which may affect any part of the genital tract in women. Female genital schistosomiasis (FGS) may cause abnormal vaginal discharge, contact bleeding, genital tumours, ectopic pregnancies and increased susceptibility to HIV. Symptoms may mimic those typical of sexually transmitted infections (STIs) and women with genital schistosomiasis may be incorrectly diagnosed. An expert consensus meeting suggested that the following findings by visual inspection should serve as proxy indicators for the diagnosis of schistosomiasis of the lower genital tract in women from S. haematobium endemic areas: sandy patches appearing as (1) single or clustered grains or (2) sandy patches appearing as homogenous, yellow areas, or (3) rubbery papules. In this atlas we aim to provide an overview of the genital mucosal manifestations of schistosomiasis in women. METHODOLOGY/PRINCIPAL FINDINGS: Photocolposcopic images were captured from women, between 1994 and 2012 in four different study sites endemic for S. haematobium in Malawi, Zimbabwe, South Africa and Madagascar. Images and specimens were sampled from sexually active women between 15 and 49 years of age. Colposcopic images of other diseases are included for differential diagnostic purposes. SIGNIFICANCE: This is the first atlas to present the clinical manifestations of schistosomiasis in the lower female genital tract. It will be freely available for online use, downloadable as a presentation and for print. It could be used for training purposes, further research, and in clinical practice.

Eosinophil granule proteins ECP and EPX as markers for a potential early-stage inflammatory lesion in female genital schistosomiasis (FGS).

BACKGROUND: Genital granulomas induced by Schistosoma haematobium eggs can manifest as different lesion types visible by colposcopy; rubbery papules (RP), homogenous sandy patches (HSP) and grainy sandy patches (GSP). Pronounced tissue eosinophilia is a candidate marker for active S. haematobium pathology, as viable schistosome egg granulomas often are eosinophil rich. Here it was investigated whether eosinophil granule proteins ECP (eosinophil cationic protein) and EPX (eosinophil protein-X) in urine and genital lavage can be used as markers for active FGS lesions. METHODS: Uro-genital samples from 118 Malagasy women were analysed for ECP and EPX by standard sandwich avidin/biotin amplified ELISA. PRINCIPAL FINDINGS: The women with RP lesions had significantly higher levels of ECP and EPX in both lavage and urine. Furthermore, women with RP lesions were significantly younger than those with GSP. This could indicate that RP lesions might be more recently established and thus represent an earlier inflammatory lesion stage. CONCLUSION: ECP in genital lavage might be a future tool aiding the identification of FGS pathology at a stage where reversibility remains a possibility following praziquantel treatment.

Promoting research integrity in Africa: an African voice of concern on research misconduct and the way forward.

African researchers and their collaborators have been making significant contributions to useful research findings and discoveries in Africa. Despite evidence of scientific misconduct even in heavily regulated research environments, there is little documented information that supports prevalence of research misconduct in Africa. Available literature on research misconduct has focused on the developed world, where credible research integrity systems are already in place. Public attention to research misconduct has lately increased, calling for attention to weaknesses in current research policies and regulatory frameworks. Africa needs policies, structural and governance systems that promote responsible conduct of research. To begin to offset this relative lack of documented evidence of research misconduct, contributors working in various research institutions from nine African countries agreed to share their experiences to highlight problems and explore the need to identify strategies to promote research integrity in the African continent. The experiences shared include anecdotal but reliable accounts of previously undocumented research misconduct, including some 'normal misbehavior' of frontline staff in those countries. Two broad approaches to foster greater research integrity are proposed including promotion of institutional and individual capacity building to instil a culture of responsible research conduct in existing and upcoming research scientist and developing deterrent and corrective policies to minimize research misconduct and other questionable research practices. By sharing these experiences and through the strategies proposed, the authors hope to limit the level of research misconduct and promote research integrity in Africa.

Pathologic mucosal blood vessels in active female genital schistosomiasis: new aspects of a neglected tropical disease.

Female genital schistosomiasis is a frequent, but neglected cause of mucosal pathology in the female genital tract. Moreover, recent studies indicate that genital mucosal lesions may increase the risk of human immunodeficiency virus (HIV) infection. In rural Africa, detailed clinical images are rarely available alongside histologic sections, and further understanding of the pathogenesis of the genital mucosal lesions is needed. These cases represent previously unreported histopathologic photomicrographs and corresponding clinical images in 2 women with genital schistosomiasis. Dilated and tortuous mucosal venules seen in the cervicovaginal mucosa were found to contain viable Schistosoma haematobium eggs surrounded by a thrombus. The presence of abnormal mucosal blood vessels may be an indication of a persistent tissue reaction to S. haematobium ova in the lower female genital tract.

Notifying partners of patients with early syphilis in Madagascar: case-finding effectiveness and public health implications.

OBJECTIVE: To evaluate the case-finding effectiveness of a clinic-based partner notification effort for early syphilis in Madagascar. METHODS: We asked index cases who had proven early syphilis to identify and provide contact information of recent sex partners (in the past 3, 6, and 12 months for primary, secondary, and early latent syphilis, respectively). Named sex partners were contacted by index cases (patient notification) or, if approved by the index case, clinic staff members (provider notification); notified of their potential exposure to syphilis; and asked to come to the clinic for evaluation. We assessed case-finding effectiveness and calculated the 'brought-to-treatment' index (number of newly-diagnosed syphilis cases per number of index cases interviewed). RESULTS: Of 565 index cases, 534 reported recent sex with at least one sex partner. A total of 3167 sex partners were reported, of whom 276 were contactable (9% of 3167). Providers notified 76% and cases notified 24% of these partners. 270 partners were contacted (98% of 276), and of these, 199 presented to the clinic for evaluation (74% of 270). A total of 99 partners tested positive for syphilis and received treatment (50% of 199). The 'brought-to-treatment' index was 0.18 (99 diagnoses per 565 index cases). CONCLUSION: Partner notification was possible in this setting, resulting in treatment of syphilis-infected individuals who otherwise would likely have remained untreated. However, given <10% of the partners reported by index cases were contactable; the results highlight the limitations of partner notification and the need for additional sexually transmitted infection control strategies.

Perceived control over condom use among sex workers in Madagascar: a cohort study.

BACKGROUND: Women's perceived control over condom use has been found to be an important determinant of actual condom use in some studies. However, many existing analyses used cross-sectional data and little quantitative information exists to characterize the relationships between perceived control and actual condom use among sex worker populations. METHODS: We assessed the association between measures of perceived condom use control and self-reported use of male condoms employing data from a longitudinal pilot study among 192 sex workers in Madagascar. RESULTS: In multivariable models, a lack of perceived control over condom use with a main partner and having a main partner ever refuse to use a condom when asked were both associated with an increased number of sex acts unprotected by condoms in the past week with a main partner (RR 1.86; 95% CI 1.21-2.85; RR 1.34; 95% CI 1.03-1.73, respectively). Conversely, no measure of condom use control was significantly associated with condom use with clients. CONCLUSION: Perceived control over condom use was an important determinant of condom use with main partners, but not clients, among sex workers in Madagascar. Programs working with sex workers should reach out to main and commercial partners of sex workers to increase male condom use.

Human papillomavirus and cervical neoplasia among female sex workers in Madagascar.

INTRODUCTION: Human papillomavirus (HPV) prevalence and type distribution were estimated among 90 female sex workers (FSWs) aged 18 to 58 years in Antananarivo, Madagascar. METHODS: A total of 90 FSWs aged 18 to 58 years in Antananarivo, Madagascar, were included in this study. Information on sexual and behavioral characteristics was obtained via a questionnaire. Exfoliated cervical cell specimens were collected for conventional cytologic examination and HPV DNA testing by polymerase chain reaction. The prevalence rates of HPV DNA and their corresponding 95% confidence intervals were stratified into the following 3 age groups: younger than 25, 25 to 34, and 35 years or older. To assess the association between HPV DNA positivity and sociodemographic and sexual behavioral factors, age-adjusted odds ratios and 95% confidence intervals were calculated using unconditional logistic regression. RESULTS: The HPV prevalence in exfoliated cervical cell specimens was 36.7%. The most common HPV types found were HPV-52 (11.1%), HPV-31 and -39 (each at 5.6%), and HPV-16 and -83 (each at 3.3%). The prevalence of low-grade squamous intraepithelial lesions was 3.3%, and that of atypical squamous cells of undetermined significance was 18.9%. No high-grade lesion was found. Although associations were imprecise, the HPV prevalence was higher among women who reported younger age at the first intercourse, contraceptive use, a history of cervical lesions, and no history of condom use. DISCUSSION: The prevalence rates of HPV and cervical lesions among FSWs in Madagascar appear higher than among FSW populations from other African countries with a relatively higher population-based prevalence of human immunodeficiency virus infection.

Promoting continuous use as a strategy for achieving adherence in a trial of the diaphragm with candidate microbicide.

Women need more choices for protection from HIV and other sexually transmitted infections (STIs). We conducted a randomized 4-week study in Madagascar in preparation for a Phase III randomized controlled trial (RCT) of the diaphragm with a candidate microbicide for STI prevention. All participants completed quantitative surveys; half participated in a qualitative interview. We advised women to wear the diaphragm at all times except for daily cleaning (rather than inserting it before intercourse). The objective of this analysis was to determine whether women who followed this "continuous use" approach more often used the diaphragm for 100% of sex acts as compared with other women. If so, this would support advising continuous diaphragm use in the upcoming RCT. To meet our objective, we analyzed qualitative data thematically, developed a measure of continuous diaphragm use based on qualitative data, and used multiple regression to evaluate the measure's association with adherence to diaphragm use during 100% of sex acts. Women who wore the diaphragm continuously had 4 times higher odds of reporting diaphragm use during 100% of sex acts (OR: 4.6, 95% CI: 1.2, 24.0). If the diaphragm proves effective against STI, continuous use may help women achieve high levels of protection.

Evaluation of azithromycin resistance in Treponema pallidum specimens from Madagascar.

Treponema pallidum resistance to azithromycin has been documented in the US, Canada, and Ireland. We found no evidence of resistance to azithromycin in specimens from 141 patients with syphilitic lesions in Madagascar suggesting resistance is geographically isolated and supporting use of azithromycin as alternative treatment for early syphilis in Madagascar.

Predictors of adherent use of diaphragms and microbicide gel in a four-arm, randomized pilot study among female sex workers in Madagascar.

BACKGROUND: Participants' protocol adherence may influence assessments of the effectiveness of new female-controlled methods for sexually transmitted infection prevention. METHODS: In 2005 we conducted a randomized pilot study among female sex workers (FSWs) in Madagascar in preparation for sexually transmitted infection prevention trial of diaphragms and a vaginal microbicide. Participants (n = 192) were randomized into 4 arms: diaphragm plus microbicide (Acidform), diaphragm plus placebo gel hydroxyethyl cellulose (HEC), Acidform alone, or HEC alone. FSWs were seen weekly for 4 weeks. Using multivariable regression with generalized estimating equations, we assessed predictors of adherent product use during all sex acts in the last week. We collapsed the gel-diaphragm arms together and the gel-only arms together for this analysis. RESULTS: Between 43% and 67% of gel-diaphragm users (varying by visit) reported using study products during all sex acts in the last week, compared with 20% to 45% of gel-only users. Adherence increased with follow-up [visit 4 vs. visit 1 risk ratio (RR) for gel-diaphragm users: 1.55, P <0.01; for gel-only users, RR: 1.58, P = 0.01]. Gel-diaphragm users whose casual partners were never aware of products (RR: 2.02, P = 0.03) and who had experienced partner violence after requesting condom use (RR: 1.45, P <0.01) were more adherent. Gel-only users reporting lower sexual frequency (1-9 weekly acts vs. >or=19 acts, RR: 1.98, P <0.01) and no sex with primary partners in the past week (RR: 1.54, P = 0.02) were more adherent. CONCLUSIONS: Gel-diaphragm users had better adherence than gel-only users, and predictors of adherence differed between groups. Addressing modifiable factors during counseling sessions may improve adherence.

Barriers to the use of modern contraceptives and implications for woman-controlled prevention of sexually transmitted infections in Madagascar.

Globally, unplanned pregnancies and sexually transmitted infections (STIs) persist as significant threats to women's reproductive health. Barriers to the use of modern contraceptives by women might inhibit uptake of novel woman-controlled methods for preventing STIs/HIV. Use of modern contraceptives and perceptions and attitudes towards contraceptive use were investigated among women in Antananarivo, Madagascar, using qualitative research. The hypothetical acceptability of the diaphragm--a woman-controlled barrier contraceptive device that also holds promise of protecting against STIs/HIV--was assessed. Women consecutively seeking care for vaginal discharge at a public health clinic were recruited for participation in a semi-structured interview (SSI) or focus group discussion (FGD). Audiotaped SSIs and FGDs were transcribed, translated and coded for predetermined and emerging themes. Of 46 participating women, 70% reported occasional use of male condoms, mostly for preventing pregnancy during their fertile days. Although women could name effective contraceptive methods, only 14% reported using hormonal contraception. Three barriers to use of modern contraceptives emerged: gaps in knowledge about the range of available contraceptive methods; misinformation and negative perceptions about some methods; and concern about social opposition to contraceptive use, mainly from male partners. These results demonstrate the need for programmes in both family planning and STI prevention to improve women's knowledge of modern contraceptives and methods to prevent STI and to dispel misinformation and negative perceptions of methods. In addition, involvement of men will probably be a critical component of increased uptake of woman-controlled pregnancy and STI/HIV prevention methods and improved health.

Sexually transmitted infections in rural Madagascar at an early stage of the HIV epidemic: a 6-month community-based follow-up study.

BACKGROUND AND OBJECTIVES: Sexually transmitted infections (STIs) in Madagascar have primarily been monitored in selected groups of patients attending STI clinics in major cities as part of the HIV surveillance program in Madagascar. GOAL OF THE STUDY: The aim of the study was to provide complementary data related to STI prevalence in a general rural population. STUDY DESIGN: STIs were investigated in 643 subjects aged 15 to 49 years as part of a cross-sectional morbidity study of urogenital schistosomiasis. Infection rates were reassessed 3 weeks and 6 months after systematic STI treatment at baseline. RESULTS: Neisseria gonorrhoeae (Ng), Chlamydia trachomatis (Ct), Mycoplasma genitalium (Mg), Trichomonas vaginalis (Tv), and/or antibodies to Treponema pallidum (Tp) were diagnosed in 125 (37.5%) of 333 women and in 83 (26.8%) of 310 men. In addition, 49% of the women and 28% of the men were infected with herpes simplex virus-2. Six (0.9%) subjects were found HIV-antibody positive. Between the 3-week and 6-month follow-up surveys Ng, Ct, and/or Mg prevalence increased most prominently in women aged 15 to 24 years. CONCLUSION: Study findings suggest that rural areas in Madagascar should be as closely monitored and assisted in STI and HIV control as their urban counterparts. Following the current consensus, young adults should constitute a priority target group in the control programs.