Background: Single-dose praziquantel (PZQ) for treating urogenital schistosomiasis has been reported as inadequate for achieving significant resolution of female genital schistosomiasis (FGS)-associated cervicovaginal lesions. This randomised controlled trial aimed to assess the efficacy and safety of a repeated PZQ-dosing regimen.Methods: The trial was conducted among women aged 15 to 34 with FGS-associated cervical lesions living in a Schistosoma haematobium-endemic area of northern Madagascar. A total of 116 women were randomly allocated to either repeated PZQ-dosing (n=58) or a single PZQ dose (n=58). All received an initial PZQ dose of 40mg/kg at baseline. In the repeated-dosing arm, additional doses were given 12 and 24 hours later and again at 5 and 10 weeks. Primary outcome was FGS-related cervical lesions at baseline compared to Week 15 follow-up. Secondary outcomes encompassed pelvic exam abnormalities, urogenital complaints, and biomarkers, including cervicovaginal S. haematobium DNA and circulating anodic antigens (CAA) in serum.Results: Excluding 21 women who were pregnant or failed to attend follow-up visits, 95 women were eligible for per-protocol treatment effect analysis. A minor and insignificant reduction in cervical lesions was observed in both of the two treatment arms at Week 15 follow-up. A clear tendency towards decline in pelvic exam abnormalities and urogenital complaints in both treatment arm groups was observed. The reduction in number of women testing positive for CAA and mean CAA values was significant in both arms but less so in the single-dose arm. Mild to moderate adverse events of equal proportions were reported in both treatment arm groups.Conclusion: FGS-associated cervical lesions appear refractory to PZQ treatment even when this is administered in a repeated-dosing regimen. In contrast, the repeated regimen seems more effective at eliminating the dwelling worm population than the single-dose regimen, as demonstrated by the CAA findings. Irrespective of dosing regimen, pelvic exam abnormalities and urogenital complaints saw equal reductions at follow-up. However, the outcome of our primary study emphasises the need for initiation early in life and a persistently maintained PZQ treatment strategy throughout childhood and adolescence to prevent lesions from establishing in the first place.Clinical trial registration: https://clinicaltrials.gov/, dentifier NCT04115072.

Lichen sclerosus (LS) is a chronic, autoimmune skin disease predominantly located in the anogenital region in women. In recent years, the role of the human microbiota in the pathogenesis of autoimmune diseases, including LS, has received interest. The study aimed to evaluate and compare the composition of the urinary, vaginal and gut microbiota in women with LS versus non-affected controls. Women diagnosed with LS (n = 16) and matched controls (n = 14) were enrolled in the study. From each participant, midstream urine, upper and lower vaginal swabs, as well as faecal samples, were collected. The microbiota composition was assessed using 16S ribosomal RNA (rRNA) gene sequencing of the V4 hypervariable region. We observed no LS-specific clustering in either of the four anatomic niches, using either hierarchical cluster analysis or weighted beta diversity metrics. However, for unweighted UniFrac, significant differences in the urinary and lower vaginal microbiota were observed when comparing women with LS to controls. These findings indicate that while the two groups have microbiota dominated by the same bacteria, variations do occur amongst less abundant bacteria. The LEfSe analysis revealed a higher relative abundance of the genus Streptococcus in the urinary and lower vaginal microbiota in women with LS compared to controls. Additionally, a higher relative abundance of phylum Euryarchaeota was observed in the gut microbiota in women with LS compared to controls. In this study, we demonstrated several differences amongst less abundant bacteria in the urinary, lower vaginal and faecal microbiota when comparing women with LS to controls. However, further research is required to assess whether these microbiota differences are causative or merely a result of the underlying LS disease.

Background: Female genital schistosomiasis (FGS) is characterised by cervico-vaginal lesions such as grainy sandy patches, homogeneous yellow sandy patches, and abnormal blood vessels. Diagnosis, treatment, and surveillance of FGS presents challenges due to the absence of diagnostic tools in endemic areas. Likewise, a tool for quantification of the lesions is missing. This study aimed to validate the digital gridded imaging technique (DGIT) for quantification of three specific cervical lesion types associated with FGS.Methods: Using the QubiFier software program, 70 cervical photographic images obtained from women diagnosed with FGS and treated with Praziquantel (PZQ) were randomly sampled for a validation study. The women lived in a S. haematobium-endemic area of Madagascar. For each image, a semi-transparent grid was applied, composed of 424 equally sized squares positioned to cover the cervix. Squares exhibiting any of the specific lesions were marked by three observers to determine the grainy sandy patches proportion (GSP), homogeneous yellow sandy patches proportion (HSP), and abnormal blood vessel proportion (BVP). To train the observers, a set of ten images was utilized, leaving 60 images for the validation. To test inter-rater reliability, the 60 cervical images were scored independently by three observers. To test intra-rater reliability, ten images were scored twice with a two-week interval. Intraclass correlation coefficient (ICC) was used as the main statistical method to assess the reliability between observers.Results: The median age of the included women was 26.5 (IQR 20.8-33.0) years, and 74% of them had detectableS. haematobiumeggs in their urine. The three proportions were found to be consistent and reliable across the observers, as well as the rescoring on Days 0 and 14. Inter-rater reliability was good for all three cervical lesion types (ICC 0.768-0.890). Intra-rater reliability was good for GSP (ICC 0.832) and excellent for HSP and BVP (ICC 0.932 and 0.982, respectively).Conclusion: In this study DGIT was validated as a potential morbidity detection method for quantification of the three lesion types associated with FGS.