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.

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.

Knowledge and perceptions about schistosomiasis among primary school children and teachers in rural KwaZulu-Natal.

BACKGROUND: Schistosomiasis is a disease caused by parasitic trematode worms of the genus Schistosoma. In 2014, over 258 million people worldwide required treatment for the disease. Schistosomiasis is known to be prevalent in the northern region of KwaZulu-Natal province of South Africa, especially among school-going children but less is known about their knowledge of the disease and their attitude towards being treated for the disease at school. METHODS: The study was a descriptive and analytical cross-sectional survey conducted through self-administered questionnaires among grades 5 and 7 learners from 10 randomly selected rural primary schools in iLembe and uThungulu, KwaZulu-Natal. Teachers from the same schools participated during the same period. RESULTS: A total of 730 learners and 78 teachers took part in the study. Among the learners, 73.2% (95% confidence interval [CI]: 69.7% - 76.4%) correctly identified freshwater contact as a risk for schistosomiasis, but only 42.7% (95% CI: 38.8% - 46.8%) knew how to prevent it. Among the teachers, 96.8% (95% CI: 87.8% - 99.4%) knew the risk and 69.0% (95% CI: 55.3%- 80.1%) knew the prevention of schistosomiasis. Almost 70% (95% CI: 65.9% - 72.8%) of the learners and 67.6% (95% CI: 42.1% - 65.6%) of the teachers reported their willingness to receive treatment with praziquantel at school. CONCLUSION: This study showed that basic knowledge about the risk of schistosomiasis among the participants was high, but the cause and prevention of the disease were less well understood. There is need to include schistosomiasis in health education both at school and through community awareness programmes.

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.

Genital schistosomiasis and its unacknowledged role on HIV transmission in the STD intervention studies.

Treatment of sexually transmitted infections (STIs) has been hypothesised to decrease HIV transmission. Although observational studies show an association between STIs and HIV, only one prospective randomised controlled trial (RCT) has confirmed this. Female genital schistosomiasis can cause genital lesions, accompanied by bloody discharge, ulcers or malodorous discharge. Genital schistosomiasis is common, starts before puberty and symptoms can be mistaken for STIs. Three observational studies have found an association between schistosomiasis and HIV. Genital lesions that develop in childhood are chronic. This paper sought to explore the possible effects of schistosomiasis on the RCTs of STI treatment for HIV prevention. In the study sites, schistosomiasis was a likely cause of genital lesions. The studies recruited women that may have had genital schistosomal lesions established in childhood. Schistosomiasis endemic areas with different prevalence levels may have influenced HIV incidence in intervention and control sites differently, and some control group interventions may have influenced the impact of schistosomiasis on the study results. Schistosomiasis is a neglected cause of genital tract disease. It may have been an independent cause of HIV incidence in the RCTs of STI treatment for HIV prevention and may have obscured the findings of these trials.

A review of female genital schistosomiasis.

In a review of the studies on genital schistosomiasis, the cervix, the Fallopian tubes, and the vagina are the most common gynaecological sites to harbour Schistosoma haematobium. Lesions are caused by host responses to dead or viable schistosomiasis eggs and may render women with genital schistosomiasis susceptible to HIV. The typical genital changes, such as sandy patches and pathological blood vessels may make women susceptible to super-infection, cause contact bleeding, decreased fertility, abortions, discharge and bleeding. Further research is needed to find simple, low-tech diagnostic methods, treatment for chronic lesions, and to explore the preventive effects of mass drug administration on symptoms, sandy patches, HPV and the HIV epidemic.

The first community-based report on the effect of genital Schistosoma haematobium infection on female fertility.

A cross-sectional study in an Schistosoma haematobium endemic area of rural Zimbabwe examined 483 resident women between the ages of 20 and 49 years who were interviewed about fertility. S. haematobium ova in genital tissue was found to be significantly associated with infertility.

Schistosomiasis PCR in vaginal lavage as an indicator of genital Schistosoma haematobium infection in rural Zimbabwean women.

Schistosoma real-time polymerase chain reaction (PCR) is sensitive and specific in urine and stool. We sought to explore the relationship between genital schistosomiasis and the Schistosoma PCR in women. PCR was run on 83 vaginal lavage samples from a rural Zimbabwean population. Women underwent clinical and colposcopic investigations, analyses for sexually transmitted infections, and genital schistosomiasis. Thirty samples were positive for Schistosoma PCR: 12 were strong and 18 were weak positive. Sensitivity (67%) and specificity (83%) were best in women below the age of 25 years. A positive schistosome PCR result was associated with S. haematobium ova in genital tissue, so-called sandy patches, and bleeding. Prevalence determined by PCR were lower and real-time PCR values were weaker in older women. The presence of Schistosoma DNA may be greater in the recent lesions (e.g., in younger women). For diagnosis in rural areas and in large studies, Schistosoma PCR could become a supplement to gynecologic examinations.

Similar cellular responses after treatment with either praziquantel or oxamniquine in Schistosoma mansoni infection.

The effect of treatment with either oxamniquine or praziquantel on S.mansoni specific IFN-gamma, IL-4, IL-5 and IL-10 was compared on PBMC which were collected pretreatment, 6 and 18 weeks post treatment. Using sandwich ELISA on the supernatants harvested from the PBMC stimulation by crude S. mansoni SEA and SWAP antigens after 5 days the levels of PBMC proliferation and cytokine production were similar according to treatment with either praziquantel or oxamniquine. Before treatment, infected groups showed low ratios, of IL-4:IFN-gamma, IL-5:IFNgamma and IL-10:IFN-gamma, indicating that IFN-gamma was high in the infected individuals. The general increase in immuno-modulation was observed post-treatment with elevated immune reactivity and cytokine production in both treatment groups. Treatment induced significant increases in levels of IL-4 (p < 0.05), IL-5 (p < 0.0001) and IL-10 (p < 0.05) cytokines 6 and 18 weeks after treatment. There were no significant differences in the increase in IL-4, IL-5 and IL-10 between children treated with praziquantel or oxamniquine. Pre-treatment IFN-gamma and IL-5 levels were positively correlated with infection (p < 0.001), while post treatment IL-4 cytokine levels were negatively correlated with baseline infection status (p < 0.001). The results suggest that treatment-induced immune responses are similar for both common anti-schistosome drugs praziquantel or oxamniquine having similar and immunizing effect.

Female genital schistosomiasis--a differential diagnosis to sexually transmitted disease: genital itch and vaginal discharge as indicators of genital Schistosoma haematobium morbidity in a cross-sectional study in endemic rural Zimbabwe.

OBJECTIVE: To examine the association between schistosomiasis and reproductive tract symptoms. METHOD: A cross-sectional study was conducted in a Schistosoma haematobium-endemic area of rural Zimbabwe. A total of 483 permanently resident adult women of Mupfure Ward aged 20-49 were interviewed and examined clinically, each providing three consecutive urine samples. Logistic regression analysis was used to control for sexually transmitted diseases (STDs). RESULTS: Women with genital sandy patches had significantly more genital itch (P = 0.009) and perceived their discharge as abnormal (P = 0.003). Eighty percent of the women who had genital itch, yellow discharge, and childhood or current waterbody contact had sandy patches. Fifty-two percent of the women with genital sandy patches did not have detectable S. haematobium ova in urine. Genital schistosomiasis was associated with stress incontinence and pollakisuria, but not with menstrual irregularities, current or previous ulcers, or tumours. CONCLUSION: Genital schistosomiasis may be a differential diagnosis to the STDs in women who have been exposed to fresh water in endemic areas. Because of the chronic nature of the disease in adults, we suggest to pay special attention to the prevention of morbidity.

Prevention of gynecologic contact bleeding and genital sandy patches by childhood anti-schistosomal treatment.

Schistosoma haematobium infection may cause genital mucosal pathology in women with and without urinary schistosomiasis. This report seeks to explore the long-term effect of anti-schistosomal treatment on the clinical manifestations of S. haematobium infection in the lower genital tract. Prior treatment was reported by 248 (47%) of 527 women. Treatment received before the age of 20 years was significantly associated with the absence of sandy patches and contact bleeding, and this association was independent of current waterbody contact. Treatment in the past five years did not influence the prevalence of gynecologic schistosoma-induced lesions. The study indicates that early treatment may be more efficient for gynecologic morbidity control. Findings warrant an exploration into several chemotherapeutic agents administered at an early age, as well as in adults.

Association between genital schistosomiasis and HIV in rural Zimbabwean women.

OBJECTIVE: To determine the association between female genital Schistosoma haematobium infection and HIV. DESIGN AND METHODS: A cross-sectional study with a 1-year follow-up. Gynecological and laboratory investigations were performed for S. haematobium and HIV. Sexually transmitted infections, demographic and urogenital history were analysed as confounders. The participants were 527 sexually active, non-pregnant, non-menopausal women between the ages of 20 and 49 years. The setting was a rural Zimbabwean community where S. haematobium related lesions were found in 46% of the women, HIV in 29% and herpes simplex type- 2 (HSV-2) in 65%. RESULTS: In permanent residents (>3 years residency), HIV was found in 41% (29/70) of women with laboratory proven genital schistosomiasis as opposed to 26% HIV positive (96/375) in the schistosomal ova negative group [odds ratio (OR), 2.1; 95% confidence interval (CI), 1.2-3.5; P = 0.008. In multivariate analysis S. haematobium infection of the genital mucosa was significantly associated with HIV seropositivity (adjusted OR, 2.9; 95% CI, 1.11-7.5; P = 0.030). All seven women who became HIV positive during the study period (seroincidence 3.1%) had signs of S. haematobium at baseline. In accordance with other studies HIV was significantly associated with HSV-2 (OR, 3.0; 95% CI, 1.7-5.3; P < 0.001), syphilis and human papillomavirus. The highest HIV prevalence (45%) was found in the 25-29 years age group. CONCLUSION: Women with genital schistosomiasis had an almost three-fold risk of having HIV in this rural Zimbabwean community. Prospective studies are needed to confirm the association.

Genital schistosomiasis in women: a clinical 12-month in vivo study following treatment with praziquantel.

Urinary schistosomiasis is known to be associated with lesions in the female genital organs, particularly with the presence of 'sandy patches' in the lower genital tract. This study sought to determine the effect of treatment with praziquantel on gynaecological schistosomiasis in residents of an area endemic for Schistosoma haematobium. A cohort study was conducted among women aged 20-49 years in rural Zimbabwe. The shape and size of lesions were mapped pre treatment and 3 and 12 months following treatment. Ova of S. haematobium were looked for in cytology smears, wet mounts, biopsies, urine and stool. Specimens were collected for detection of sexually transmitted diseases and cancer. At baseline, almost half of the 527 women included in the study had sandy patches. Although urinary ova excretion decreased following treatment (odds ratio 10.3, 95% CI 3.8-27.8, P<0.001), praziquantel treatment was not associated with a significant reduction in genital lesions or contact bleeding (P=0.31-0.94). Sandy patches remained strongly associated with contact bleeding and vessel abnormalities even after treatment. Findings were independent of HIV status. Such lesions, which are common and apparently refractory to treatment for at least 12 months, may be an important risk factor for both the acquisition and transmission of HIV.

Simple clinical manifestations of genital Schistosoma haematobium infection in rural Zimbabwean women.

Up to 75% of women with urinary schistosomiasis have Schistosoma haematobium ova in the genitals. This study aimed to describe the prevalence of gynecologic S. haematobium infection and to differentiate the disease from sexually transmitted infections (STIs). Gynecologic and laboratory investigations for S. haematobium and STIs were performed in 527 women between the ages of 20 and 49 in rural Zimbabwe. Genital homogenous yellow and/or grainy sandy patches, the commonest type of genital pathology, were identified in 243 (46%) women. Grainy sandy patches were significantly associated with S. haematobium ova only. Genital S. haematobium ova was also significantly associated with homogenous yellow sandy patches, mucosal bleeding, and abnormal blood vessels. The presence of ova was not a predictor for ulcers, papillomata, leukoplakia, polyps, or cell atypia. Mucosal sandy patches seem to be pathognomonic for S. haematobium infection in the female genitals. Coexistence of ova and other lesions may not be causal.

Herpes simplex virus type 2 prevalence of epidemic proportions in rural Zimbabwean women: association with other sexually transmitted infections.

INTRODUCTION: Syndromic management of sexually transmitted infections (STIs) is one important strategy in human immunodeficiency virus (HIV) prevention in developing countries, but there is a scarcity of rural community-based data on the relative prevalences of the STIs. We sought to determine the prevalences of the STIs and their clinical correlates in rural Zimbabwean women. METHODS: A cross-sectional study was conducted among 527 sexually active, non-pregnant, non-menopausal women between the ages of 20 and 49 years. RESULTS: The seroprevalence for herpes simplex virus type 2 (HSV-2), HIV, trichomoniasis and syphilis were 64.5, 29.3, 24.7 and 6.2% respectively. HSV-2 seropositivity was significantly associated with current non-syphilitic ulcers (adjusted odds ratio [OR] 4.91, 95% confidence interval [CI] 1.08-22.34, p = 0.040). HSV-2 seroprevalence peaked at the age of 35 whereas HIV peaked at 25. The two diseases were strongly associated (OR 2.92, 95% CI 1.85-4.65, p < 0.001). CONCLUSION: There is evidence of rural epidemics of both HSV-2 and HIV, and a change in the aetiology of genital ulcers in rural Zimbabwe.

Urinary schistosomiasis in Zimbabwean school children: predictors of morbidity.

BACKGROUND: The morbid effects of urinary bilharziasis are becoming more evident with the advent of sophisticated diagnostics such as ultrasound. However, such diagnosis of Schistosoma haematobium morbidity is often hampered by lack of funds, proper equipment, or training. OBJECTIVE: We performed a cross-sectional investigation of schoolchildren in a highly endemic area of east central Zimbabwe in order to assess the utility of a number of simple clinical indicators to predict Schistosoma haematobium morbidity. METHODS: Prevalence and intensity of S. haematobium infection was determined in 551 schoolchildren, with ultrasound examination of the kidneys and bladder performed on 222. The association of a number of demographic, parasitological, and clinical parameters with clinical outcome was evaluated. RESULTS: Overall, 60% of the children were infected with S. haematobium . Although lacking specificity, proteinuria and parasite eggs count best predicted bladder pathology. Presence of kidney dilation was associated with fatigue and pain upon urination, but these variables were not very sensitive. CONCLUSIONS: None of the variables assessed were ideal predictors of morbidity. However, the results suggest that a combination of inexpensive, simple indicators may allow for improved targeting of S. haematobium treatment to those with severe morbidity and better monitoring of the progress of control campaigns when more expensive diagnostic methods are not available.

Human papillomavirus in a rural community in Zimbabwe: the impact of HIV co-infection on HPV genotype distribution.

Cervical cancer is a leading cause of cancer-related deaths in developing countries, and the human papillomavirus (HPV) is linked etiologically to cervical cancer. Hence, a vaccine which prevents HPV-associated cervical cancer would have the most impact in developing countries, including the African continent. The type-specific immune response towards HPV virus-like particles, in combination with geographical variation in the prevalence of HPV, necessitates the presence of multiple HPV type antigens in a single vaccine cocktail in order to provide relevant protection. We aimed to investigate whether co-infection with HIV, which is highly prevalent in Africa, plays a role in HPV genotype distribution. After informed consent, HPV detection by GP5+/6+ PCR and HIV detection by serology was carried out on 236 women from the rural north-western part of Zimbabwe. The prevalence of HPV was higher in HIV positive women (54%) than in HIV negative women (27%). Certain HPV types (HPV types 11, 39, 43, 51, and 59, P-values ranging from 0.017 to 0.067) occurred more frequently in HIV positive women. Only high-risk HPV, and not HIV, was associated significantly with cervical intraepithelial neoplasia in multiple regression analysis. In conclusion, a high prevalence of HPV was found in a rural community, where regular Papanicolaou (Pap) smears would be a logistic and economic impossibility, but where free vaccination programmes against other infections are already established. The results suggest that HIV co-infection may have an impact on HPV genotype distribution.

Urinary tract pathology attributed to Schistosoma haematobium: does parasite genetics play a role?

Disease outcome in persons infected with Schistosoma haematobium varies dramatically, ranging from mild symptoms to severe damage of the kidneys and/or bladder. We used ultrasonography to characterize the extent of urinary tract pathology of infected children in Zimbabwe, and random genetic markers to examine the relationship between genetic diversity of S. haematobium and clinical outcome. One hundred thirty-three parasite isolates from 12 students with mild lesions and 13 with severe lesions were compared. Using four randomly amplified polymorphic DNA (RAPD) markers, we scored parasite allelic frequencies at 53 loci. Although parasite heterogeneity did not differ, allelic frequencies at eight loci differed significantly between the mild and severe groups. Parasite isolates were analyzed further using a modified cluster analysis that segregated the population into 13 clusters of associated genotypes. Three clusters were significantly over-represented in children with severe lesions. Our findings, although preliminary, suggest that parasite genetic associations may be important in clinical outcome.

Chemotherapy-induced, age-related changes in antischistosome antibody responses.

Humoral responses directed against Schistosoma mansoni soluble egg antigen were studied in Zimbabwean children before and after treatment with either praziquantel (PZQ) or oxamniquine (OXAM). Treated children showed a significant increase in the proportion producing IgE and IgG3 and in mean levels of IgE, IgM, IgG3 six weeks post-treatment. At 18 weeks post-treatment, the proportion of treated children producing IgA, IgE, and IgG3 increased while the proportion producing IgG1 and IgG4 decreased. Mean levels of IgA, IgE, and IgG3 were higher than pre-treatment levels while levels of IgG1, IgG4 and IgM were lower. Statistical analyses showed that the magnitude of change in levels of IgE, IgM and IgG3 at 6 weeks post-treatment and of IgE, IgG3 and IgG4 at 18 weeks post-treatment was significantly greater in treated compared to untreated children, and there were no significant differences in immune responses between children treated with praziquantel and those treated with oxamniquine. The magnitude of change in IgE at 6 and 18 weeks, IgM at 6 weeks and IgG3 at 18 weeks post-treatment were significantly associated with age in treated but not in untreated children, with the change being greater in younger children. This suggests that treatment induced a change in the age-antibody relationship for these isotypes, and that the age-antibody relationship is not robust to chemotherapy. Pre-treatment infection levels were significantly associated (positive correlation) with the magnitude of change for IgE and IgG3 at 18 weeks post-treatment. Taken together, these results indicate that the age-antibody relationship observed in these children is due, at least in part, to cumulative host experience of parasite antigens and not host age alone.

Reference values and predictors of white blood cell subset counts: a cross-sectional study among HIV seronegative pregnant women in Zimbabwe.

OBJECTIVE: To identify predictors and develop reference values of white blood cell subset counts for pregnant black women in Zimbabwe. STUDY DESIGN: In this cross-sectional study, multiple linear regression (MLR) analysis was employed to assess the relationship of WBC subset counts with age, gestational age, gravidity, season, serum retinol, beta-carotene, ferritin, folate and alpha-1 antichymotrypsin among 998 women 22-35 weeks pregnant attending antenatal care (ANC) in Harare, Zimbabwe. RESULTS: Mean age was 24.0 (95% CI; 23.6-24.4), range 14-45 years. The mean gestational age was 29.2 (95% CI; 29.0-29.4), range 22-35 weeks. Median gravidity was 2, range 1-9. Predictors of neutrophil counts were gestational age, season and serum ferritin, the latter in interaction with gravidity (interaction, p = 0.016). Mean lymphocyte count was 0.13 x 10(9)cells/l higher in gravida >4 than gravida 1-3, and 0.35 x 10(9)cells/l higher in the late rainy than other seasons. Predictors of monocyte counts were gestational age, serum folate and season, while eosinophil counts declined with advancing gestation. Reference values adjusted or unadjusted for identified predictors were different from those of pregnant and non-pregnant white women reported in the literature. CONCLUSIONS: Gravidity, season and micronutrient status influence WBC counts during pregnancy and therefore are of physiological and clinical importance. WBC reference values in the literature were not applicable obviating the need for local reference values.