Schistosomiasis is an acute and chronic disease caused by parasitic worms, that can take two main forms: intestinal or urogenital(4). According to the World Health Organization (WHO), in 2019 there were almost 240 million schistosomiasis infections worldwide, causing an estimated 3.3 million disability-adjusted life-years(2). The number of deaths due to schistosomiasis is estimated between 24,067 and 200,000 globally each year, the highest mortality among the neglected tropical diseases recognized by the WHO(5). Sub-Saharan African bears the majority of the global burden, reporting at least 93% of cases(6).
Schistosomiasis is transmitted through contact with contaminated fresh water sources during normal daily activities, like washing, bathing, cooking, or swimming (Fig. 1)(6, 7). Although there are a several species of parasitic worms that can cause schistosomiasis, approximately two-thirds of cases are due to infection with S. haematobium, the primary cause of urogenital disease including female genital schistosomiasis (FGS) which is estimated to affect up to 56 million women and girls in Africa(8). For example, a pilot study conducted in four rural communities in Ogun state in Nigeria showed schistosomiasis infection rates for women of up to 47%(9). In Ghana, urinary schistosomiasis prevalence among women in the Volta basin was 24.8% while 10.6% of them were diagnosed with female genital schistosomiasis (FGS)(10).
Urogenital schistosomiasis affects both the urinary and genital track of infected individuals when eggs released by adult worms implant in tissue in the urogenital system of the infected host. The urinary signs and symptoms are easily recognized, with bloody urine often being the first sign of infection and typically what is described in medical training. Female genital symptoms include vaginal discharge, post-coital bleeding, genital burning, and/or pelvic pain(5). If left untreated, infection can lead to more severe complications related to women’s reproductive health, characterized by anemia, sub- or infertility, spontaneous abortion, and ectopic pregnancy(11). Community-based studies in two S. haematobium-endemic areas in Zimbabwe, reported that 15% of women suffered from infertility with an odds ratio (OR) of 3.6 for FGS(12). A study analyzing DHS data in Ethiopia, Uganda, Kenya, and Tanzania demonstrated that women in S. haematobium-endemic areas had a significantly higher OR for infertility than those living in non-endemic areas suggesting that FGS may be an underlying factor(12). A study conducted in Ghana, comparing 41 pregnant women infected with S. haematobium to 500 noninfected women, showed that the risk of premature birth was higher (34.8%) in infected women, compared to the others (23.8%)(13). However, reliable and detailed data on the consequences of schistosomiasis and birth outcomes is still limited.
In addition to the pathology from the infection directly, FGS is a plausible risk factor for HIV acquisition(14–17) and cervical cancer(11, 18, 19) due to the tissue pathology, mucosal changes, and local immunologic modulations associated with FGS(20, 21). In fact, studies across sub-Saharan Africa have shown a strong association between HIV prevalence and FGS(5). For example, a case-controlled study in rural Zimbabwe showed that women with FGS had a three-fold risk of having HIV(17). A study looking across 43 sub-Saharan countries found that for every S. haematobium infection per 100 individuals, there was a relative increase of 2.9% in HIV prevalence suggesting an association between infection with S. haematobium and HIV(14). The local inflammatory response to the parasite eggs includes HIV target cells (CD4 + T lymphocytes and macrophages)(22) and coupled with the friable epithelium and lesions which can cause bleeding during coitus creates a permissive setting for HIV transmission(23). Therefore, addressing schistosomiasis can improve women’s overall reproductive health and decrease vulnerability to other important reproductive health threats such as HIV. Recently, a WHO Technical Working Group on HIV and Schistosomiasis reviewed and summarized the evidence of the association between HIV and schistosomiasis and put forth concrete actions to control the HIV/schistosomiasis syndemic in adolescent girls and young women (AGYW)(3, 23). In their systematic review(23) the authors, members of the working group, highlighted the need for training in health care workers as a critical gap to improve the condition of AGYW suffering from both diseases. The work we are presenting through this article, builds upon this evidence, underscoring the need for wider awareness on the disease’s characteristics, preventive measures, diagnostic and treatment amongst practitioners that care for the sexual and reproductive health of women and girls.
Many non-specific symptoms such as vaginal discharge and pain that patients present with result in many cases being misdiagnosed as sexuality transmitted infections (STI). The diagnosis of FGS is made clinically through colposcopy or visual inspection identifying lesions on the cervix or vaginal tissue(24). Lesions are described in the WHO FGS Atlas(25) and include intra-vaginal classic grainy sandy patches, single or clustered grains, homogenous yellow patches, rubbery papules, and abnormal blood vessels as seen in the images in Fig. 2(25). In addition, some case reports show hypertrophic or ulcerative lesions on the vagina, vulva, or cervix(26–28). These lesions have been linked histopathologically, in some cases, to the presence of eggs in the tissue causing inflammatory reactions. Detection of these lesions requires colposcopy, or for large lesions, via visual inspection with a speculum or biopsy. However, colposcopes are not commonly available in most rural endemic settings and therefore most infected individuals are never diagnosed. Even if women are referred to higher levels in the health system, the lesions are often not identified as FGS and again proper treatment is not provided.
When an FGS case is suspected, the appropriate treatment of Schistosoma infection is with 40mg/kg of praziquantel as a single dose based weight or according to local guidelines with repeated treatment if risk factors persist. Treatment for school-aged children is donated by Merck and freely available as a community-based treatment regardless of infection status in a process known as mass drug (or medicine) administration (MDA). As infection in endemic settings is frequently asymptomatic until parasite loads increase and tissue damage has progressed, prevalence at the community level in school-aged children will trigger MDA to reduce morbidity and progression of disease in the population. Individual patient treatment for FGS is also with single dose treatment although clinical trials are ongoing to see if different treatment regimens are more effective. Treatment is most effective when given early; however, the potential for reinfection remains high without improved access to safe water(29). Lesions found later in life may not resolve with antiparasitic treatments as some eggs remain in tissues despite the death of the adult worms and because of fibrosis and calcification of the lesions. More studies are needed on the treatment of advanced disease.
Recognition and proper treatment of FGS is greatly hampered by the fact that it may not be part of standard medical training. In addition, awareness of the disease is low in both affected communities and health systems of endemic countries leaving women little recourse to address the symptoms and complications associated with FGS(2). Figure 3 shows the most common cycles of FGS misdiagnosis and treatment. In cycle A, a woman is exposed to contaminated water through activities of daily living and becomes ill. She most commonly seeks care at the local health post where, based on symptoms that likely including vaginal discharge and pain, she is presumptively treated for sexually transmitted infections (STI). The woman would then go to the local pharmacy in the village and get antibiotic treatment for STI. When symptoms do not resolve, treatment may be repeated with non-compliance or re-infection being suspected. Eventual referral to the next level health facility would typically require transport and a longer time away from home and household or work responsibilities. At the next level facility depicted in cycle C, there would likely be a further exam but with a similar outcome, perhaps treating with next-line therapy for STI. The woman would return home and again receive antibiotic treatment and again symptoms would not resolve. This process could be repeated with cultures taken and while awaiting results repeating treatment. Without resolution, the patient would then be potentially referred to the next level facility in cycle D. Upon referral the patient would receive a pelvic exam and cultures and presumptive treatment may commonly be repeated again. If a pelvic exam is done and a lesion visualized, biopsies may be taken which again would result in treatment delays and potentially more aggressive treatment if presumptive diagnosis of cervical cancer is suspected. Every visit, treatment, and referral point in this cycle has financial and opportunity costs for the woman and is a potential loss to follow up. Each heath care visit also represents an opportunity to break this cycle if FGS is suspected, providing the opportunity to go from the pharmacy with the correct treatment and return to an improved state of health. This image also shows the potential role that the pharmacy can play as a common point in the referral cycle. These cycles of misdiagnosis and mistreatment demonstrate the need to increase awareness and knowledge around detection and proper treatment of FGS at all levels of the health care system so women and girls no longer have to suffer the consequences of inadvertent misdiagnosis and improper treatment. As a first step, a consistent framework is needed for training health professionals on how to diagnose, treat, and prevent FGS.
As part of the FGS Accelerated Scale Together (FAST) Package project and in collaboration with the WHO NTD department, Bridges to Development and the Geneva Learning Foundation conducted a virtual interactive workshop to establish the competencies that are required train health workers in FGS at various levels of the health systems in endemic settings. Increased awareness of and training for FGS will ultimately help endemic countries address the needs of AGYW at risk of FGS within their health systems.