The Association Between Female Genital Schistosomiasis and Other Infections of the Lower Genital Tract in Adolescent Girls and Young Women: A Cross-Sectional Study in South Africa.

OBJECTIVES/PURPOSES OF THE STUDY: This study aimed to explore the relationship between female genital schistosomiasis (FGS), sexually transmitted infections, bacterial vaginosis, and yeast among young women living in Schistosoma haematobium-endemic areas. METHODS: In a cross-sectional study of young women, sexually active, aged 16 to 22 years in rural KwaZulu-Natal, South Africa, in 32 randomly selected rural schools in schistosomiasis-endemic areas, the authors performed gynecological and laboratory investigations, diagnosed FGS and other infections, and did face-to-face interviews. RESULTS: Female genital schistosomiasis was the second most prevalent current genital infection (23%), significantly more common in those who had urinary schistosomiasis (35%), compared with those without (19%, p < .001). In the FGS-positive group, 35% had human papillomavirus compared with 24% in the FGS-negative group (p = .010). In the FGS-positive group, 37% were seropositive for herpes simplex virus infection, compared with 30% in the FGS-negative group (p = .079). There were significantly fewer chlamydia infections among women with FGS (20%, p = .018) compared with those who did not have FGS (28%). CONCLUSIONS: Female genital schistosomiasis was the second most common genital infection after herpes simplex virus. Human papillomavirus infection was significantly associated with FGS, but Chlamydia was negatively associated with FGS. Women with FGS may have had more frequent contact with the health system for genital discharge. The results show the importance of the inclusion of FGS in the national management protocols for genital infections in areas endemic for S. haematobium and highlight a more comprehensive approach to diagnosis and genital disease management.

Cervical ectopy: associations with sexually transmitted infections and HIV. A cross-sectional study of high school students in rural South Africa.

OBJECTIVES: It has been hypothesised that ectopy may be associated with increased susceptibility to sexually transmitted infections (STIs). In this cross-sectional study, we wanted to explore the association between STIs (including HIV) and cervical ectopy. METHODS: We included 700 sexually active young women attending randomly selected high schools in a rural district in KwaZulu-Natal, South Africa. The district is endemic of HIV and has a high prevalence of STIs. We did computer-assisted measurements of the ectocervical area covered by columnar epithelium (ectopy) in colposcopic images and STI analyses on cervicovaginal lavage and serum samples. All participating women answered a questionnaire about sexual behaviour and use of contraceptives. RESULTS: The mean age was 19.1 years. Ectopy was found in 27.2%, HIV in 27.8%, chlamydia in 25.3% and gonorrhoea in 15.6%. We found that age, parity, chlamydia and gonorrhoea, years since menarche, years since sexual debut and number of sexual partners were associated with ectopy. In multivariate analysis with chlamydia infection as the dependent variable, women with ectopy had increased odds of having chlamydia infection (adjusted OR 1.78, p=0.033). In women under 19 years of age, we found twofold higher odds of being HIV-positive for those with ectopy (OR 2.19, p=0.014). CONCLUSIONS: In conclusion, cervical ectopy is associated with Chlamydia trachomatis infection and HIV in the youngest women.

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.

A systematic review of handheld tools in lieu of colposcopy for cervical neoplasia and female genital schistosomiasis.

BACKGROUND: Visualization of the lesions in the lower genital tract is the mainstay for diagnosis of the four lesions found in female genital schistosomiasis (FGS), but colposcopes are generally not available in low-resource settings. OBJECTIVE: We sought to review handheld devices that could potentially be used for FGS diagnosis. SEARCH STRATEGY: We searched Medline and Embase 2015-2019 for handheld devices used in cervical cancer screening and FGS diagnosis. SELECTION CRITERIA: We excluded studies that did not compare the device to standard-of-care colposcopes or histopathology. MAIN RESULTS AND CONCLUSION: In 11 studies, four handheld colposcopes, two smartphones, and one compact digital camera were evaluated. Two handheld colposcopes were found to be potentially adequate for FGS diagnosis, namely Gynocular and Mobile ODT. The smartphones and digital camera did not have sufficient magnification to diagnose grainy sandy patches, one of the FGS lesion types. Customized software should be made to support the diagnosis of both FGS and cervical neoplasia. Real-time postgraduate training and quality control should be considered in future studies of handheld colposcopes. For patients from schistosomiasis endemic areas, we recommend that handheld devices are used for FGS. Studies are needed to determine which of the two devices is most adequate for FGS diagnosis in schistosomiasis endemic areas.

Evaluating diagnostic indicators of urogenital Schistosoma haematobium infection in young women: A cross sectional study in rural South Africa.

BACKGROUND: Urine microscopy is the standard diagnostic method for urogenital S. haematobium infection. However, this may lead to under-diagnosis of urogenital schistosomiasis, as the disease may present itself with genital symptoms in the absence of ova in the urine. Currently there is no single reliable and affordable diagnostic method to diagnose the full spectrum of urogenital S. haematobium infection. In this study we explore the classic indicators in the diagnosis of urogenital S. haematobium infection, with focus on young women. METHODS: In a cross-sectional study of 1237 sexually active young women in rural South Africa, we assessed four diagnostic indicators of urogenital S. haematobium infection: microscopy of urine, polymerase chain reaction (PCR) of cervicovaginal lavage (CVL), urogenital symptoms, and sandy patches detected clinically in combination with computerised image analysis of photocolposcopic images. We estimated the accuracy of these diagnostic indicators through the following analyses: 1) cross tabulation (assumed empirical gold standard) of the tests against the combined findings of sandy patches and/or computerized image analysis and 2) a latent class model of the four indicators without assuming any gold standard. RESULTS: The empirical approach showed that urine microscopy had a sensitivity of 34.7% and specificity of 75.2% while the latent class analysis approach (LCA) suggested a sensitivity of 81.0% and specificity of 85.6%. The empirical approach and LCA showed that Schistosoma PCR in CVL had low sensitivity (14.1% and 52.4%, respectively) and high specificity (93.0% and 98.0, respectively). Using LCA, the presence of sandy patches showed a sensitivity of 81.6 and specificity of 42.4%. The empirical approach and LCA showed that urogenital symptoms had a high sensitivity (89.4% and 100.0%, respectively), whereas specificity was low (10.6% and 12.3%, respectively). CONCLUSION: All the diagnostic indicators used in the study had limited accuracy. Using urine microscopy or Schistosoma PCR in CVL would only confirm a fraction of the sandy patches found by colposcopic examination.

Characteristics of Blood Vessels in Female Genital Schistosomiasis: Paving the Way for Objective Diagnostics at the Point of Care.

BACKGROUND: The mucosal changes associated with female genital schistosomiasis (FGS) encompass abnormal blood vessels. These have been described as circular, reticular, branched, convoluted and having uneven calibre. However, these characteristics are subjective descriptions and it has not been explored which of them are specific to FGS. METHODS: In colposcopic images of young women from a schistosomiasis endemic area, we performed computerised morphologic analyses of the cervical vasculature appearing on the mucosal surface. Study participants where the cervix was classified as normal served as negative controls, women with clinically diagnosed FGS and presence of typical abnormal blood vessels visible on the cervical surface served as positive cases. We also included women with cervical inflammatory conditions for reasons other than schistosomiasis. By automating morphological analyses, we explored circular configurations, vascular density, fractal dimensions and fractal lacunarity as parameters of interest. RESULTS: We found that the blood vessels typical of FGS are characterised by the presence of circular configurations (p < 0.001), increased vascular density (p = 0.015) and increased local connected fractal dimensions (p = 0.071). Using these features, we were able to correctly classify 78% of the FGS-positive cases with an accuracy of 80%. CONCLUSIONS: The blood vessels typical of FGS have circular configurations, increased vascular density and increased local connected fractal dimensions. These specific morphological features could be used diagnostically. Combined with colourimetric analyses, this represents a step towards making a diagnostic tool for FGS based on computerised image analysis.

Association of Urogenital Symptoms with History of Water Contact in Young Women in Areas Endemic for S. haematobium. A Cross-Sectional Study in Rural South Africa.

Female genital schistosomiasis is a neglected tropical disease caused by Schistosoma haematobium. Infected females may suffer from symptoms mimicking sexually transmitted infections. We explored if self-reported history of unsafe water contact could be used as a simple predictor of genital schistosomiasis. In a cross-sectional study in rural South Africa, 883 sexually active women aged 16-22 years were included. Questions were asked about urogenital symptoms and water contact history. Urine samples were tested for S. haematobium ova. A score based on self-reported water contact was calculated and the association with symptoms was explored while adjusting for other genital infections using multivariable logistic regression analyses. S. haematobium ova were detected in the urine of 30.5% of subjects. Having ova in the urine was associated with the water contact score (p < 0.001). Symptoms that were associated with water contact included burning sensation in the genitals (p = 0.005), spot bleeding (p = 0.012), abnormal discharge smell (p = 0.018), bloody discharge (p = 0.020), genital ulcer (p = 0.038), red urine (p < 0.001), stress incontinence (p = 0.001) and lower abdominal pain (p = 0.028). In S. haematobium endemic areas, self-reported water contact was strongly associated with urogenital symptoms. In low-resource settings, a simple history including risk of water contact behaviour can serve as an indicator of urogenital schistosomiasis.

The first step toward diagnosing female genital schistosomiasis by computer image analysis.

Schistosoma haematobium causes female genital schistosomiasis (FGS), which is a poverty-related disease in sub-Saharan Africa. Furthermore, it is co-endemic with human immunodeficiency virus (HIV), and biopsies from genital lesions may expose the individual to increased risk of HIV infection. However, microscopy of urine and hematuria are nonspecific and insensitive predictors of FGS and gynecological investigation requires extensive training. Safe and affordable diagnostic methods are needed. We explore a novel method of diagnosing FGS using computer color analysis of colposcopic images. In a cross-sectional study on young women in an endemic area, we found strong associations between the output from the computer color analysis and both clinical diagnosis (odds ratio [OR] = 5.97, P < 0.001) and urine microscopy for schistosomiasis (OR = 3.52, P = 0.004). Finally, using latent class statistics, we estimate that the computer color analysis yields a sensitivity of 80.5% and a specificity of 66.2% for the diagnosis of FGS.

Colourimetric image analysis as a diagnostic tool in female genital schistosomiasis.

Female genital schistosomiasis (FGS) is a highly prevalent waterborne disease in some of the poorest areas of sub-Saharan Africa. Reliable and affordable diagnostics are unavailable. We explored colourimetric image analysis to identify the characteristic, yellow lesions caused by FGS. We found that the method may yield a sensitivity of 83% and a specificity of 73% in colposcopic images. The accuracy was also explored in images of simulated inferior quality, to assess the possibility of implementing such a method in simple, electronic devices. This represents the first step towards developing a safe and affordable aid in clinical diagnosis, allowing for a point-of-care approach.

Schistosoma haematobium infection and CD4+ T-cell levels: a cross-sectional study of young South African women.

Schistosoma (S.) haematobium causes urogenital schistosomiasis and has been hypothesized to adversely impact HIV transmission and progression. On the other hand it has been hypothesized that HIV could influence the manifestations of schistosomiasis. In this cross-sectional study, we explored the association between urogenital S. haematobium infection and CD4 cell counts in 792 female high-school students from randomly selected schools in rural KwaZulu-Natal, South Africa. We also investigated the association between low CD4 cell counts in HIV positive women and the number of excreted schistosome eggs in urine. Sixteen percent were HIV positive and 31% had signs of urogenital schistosomiasis (as determined by genital sandy patches and / or abnormal blood vessels on ectocervix / vagina by colposcopy or presence of eggs in urine). After stratifying for HIV status, participants with and without urogenital schistosomiasis had similar CD4 cell counts. Furthermore, there was no significant difference in prevalence of urogenital schistosomiasis in HIV positive women with low and high CD4 cell counts. There was no significant difference in the number of eggs excreted in urine when comparing HIV positive and HIV negative women. Our findings indicate that urogenital schistosomiasis do not influence the number of circulating CD4 cells.

Sustained Toll-Like Receptor 9 Activation Promotes Systemic and Cardiac Inflammation, and Aggravates Diastolic Heart Failure in SERCA2a KO Mice.

AIM: Cardiac inflammation is important in the pathogenesis of heart failure. However, the consequence of systemic inflammation on concomitant established heart failure, and in particular diastolic heart failure, is less explored. Here we investigated the impact of systemic inflammation, caused by sustained Toll-like receptor 9 activation, on established diastolic heart failure. METHODS AND RESULTS: Diastolic heart failure was established in 8-10 week old cardiomyocyte specific, inducible SERCA2a knock out (i.e., SERCA2a KO) C57Bl/6J mice. Four weeks after conditional KO, mice were randomized to receive Toll-like receptor 9 agonist (CpG B; 2µg/g body weight) or PBS every third day. After additional four weeks, echocardiography, phase contrast magnetic resonance imaging, histology, flow cytometry, and cardiac RNA analyses were performed. A subgroup was followed, registering morbidity and death. Non-heart failure control groups treated with CpG B or PBS served as controls. Our main findings were: (i) Toll-like receptor 9 activation (CpG B) reduced life expectancy in SERCA2a KO mice compared to PBS treated SERCA2a KO mice. (ii) Diastolic function was lower in SERCA2a KO mice with Toll-like receptor 9 activation. (iii) Toll-like receptor 9 stimulated SERCA2a KO mice also had increased cardiac and systemic inflammation. CONCLUSION: Sustained activation of Toll-like receptor 9 causes cardiac and systemic inflammation, and deterioration of SERCA2a depletion-mediated diastolic heart failure.

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.

Effect of female genital schistosomiasis and anti-schistosomal treatment on monocytes, CD4+ T-cells and CCR5 expression in the female genital tract.

BACKGROUND: Schistosoma haematobium is a waterborne parasite that may cause female genital schistosomiasis (FGS), characterized by genital mucosal lesions. There is clinical and epidemiological evidence for a relationship between FGS and HIV. We investigated the impact of FGS on HIV target cell density and expression of the HIV co-receptor CCR5 in blood and cervical cytobrush samples. Furthermore we evaluated the effect of anti-schistosomal treatment on these cell populations. DESIGN: The study followed a case-control design with post treatment follow-up, nested in an on-going field study on FGS. METHODS: Blood and cervical cytobrush samples were collected from FGS negative and positive women for flow cytometry analyses. Urine samples were investigated for schistosome ova by microscopy and polymerase chain reaction (PCR). RESULTS: FGS was associated with a higher frequency of CD14+ cells (monocytes) in blood (11.5% in FGS+ vs. 2.2% in FGS-, p = 0.042). Frequencies of CD4+ cells expressing CCR5 were higher in blood samples from FGS+ than from FGS- women (4.7% vs. 1.5%, p = 0.018). The CD14+ cell population decreased significantly in both compartments after anti-schistosomal treatment (p = 0.043). Although the frequency of CD4+ cells did not change after treatment, frequencies of CCR5 expression by CD4+ cells decreased significantly in both compartments (from 3.4% to 0.5% in blood, p = 0.036; and from 42.4% to 5.6% in genital samples, p = 0.025). CONCLUSIONS: The results support the hypothesis that FGS may increase the risk of HIV acquisition, not only through damage of the mucosal epithelial barrier, but also by affecting HIV target cell populations, and that anti-schistosomal treatment can modify this.

HIV target cells in Schistosoma haematobium-infected female genital mucosa.

The parasite Schistosoma haematobium frequently causes genital lesions in women and could increase the risk of human immunodeficiency virus (HIV) transmission. This study quantifies the HIV target cells in schistosome-infected female genital mucosa. Cervicovaginal biopsies with and without schistosomiasis were immunostained for quantification of CD4(+) T lymphocytes (CD3, CD8), macrophages (CD68), and dendritic Langerhans cells (S100 protein). We found significantly higher densities of genital mucosal CD4(+) T lymphocytes and macrophages surrounding schistosome ova compared with cervicovaginal mucosa without ova (P = 0.034 and P = 0.018, respectively). We found no increased density of Langerhans cells (P = 0.25). This study indicates that S. haematobium may significantly increase the density of HIV target cells (CD4(+) T lymphocytes and macrophages) in the female genitals, creating a beneficial setting for HIV transmission. Further studies are needed to confirm these findings and to evaluate the effect of anti-schistosomal treatment on female genital schistosomiasis.