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Various global health initiatives are currently advocating the elimination of schistosomiasis within the next decade. Schistosomiasis is a highly debilitating tropical infectious disease with severe burden of morbidity and thus operational research accurately evaluating diagnostics that quantify the epidemic status for guiding effective strategies is essential. Latent class models (LCMs) have been generally considered in epidemiology and in particular in recent schistosomiasis diagnostic studies as a flexible tool for evaluating diagnostics because assessing the true infection status (via a gold standard) is not possible. However, within the biostatistics literature, classical LCM have already been criticised for real-life problems under violation of the conditional independence (CI) assumption and when applied to a small number of diagnostics (i.e. most often 3-5 diagnostic tests). Solutions of relaxing the CI assumption and accounting for zero-inflation, as well as collecting partial gold standard information, have been proposed, offering the potential for more robust model estimates. In the current article, we examined such approaches in the context of schistosomiasis via analysis of two real datasets and extensive simulation studies. Our main conclusions highlighted poor model fit in low prevalence settings and the necessity of collecting partial gold standard information in such settings in order to improve the accuracy and reduce bias of sensitivity and specificity estimates., Author summary Accurate schistosomiasis diagnosis is essential to assess the impact of large scale and repeated mass drug administration to control or even eliminate this disease. However, in schistosomiasis diagnostic studies, several inherent study design issues pose a real challenge for the currently available statistical tools used for diagnostic modelling and associated data analysis and conclusions. More specifically, those study design issues are: 1) the inclusion of small number of diagnostic tests (i.e. most often five), 2) non formal consensus about a schistosomiasis gold standard, 3) the contemporary use of relatively small sample sizes in relevant studies due to lack of research funding, 4) the differing levels of prevalence of the studied disease even within the same area of one endemic country and 5) other real world factors such as: the lack of appropriate equipment, the variability of certain methods due to biological phenomena and training of technicians across the endemic countries because of scarce financial resources contributing to the existing lack of a schistosomiasis gold standard. The current study aims to caution practitioners from blindly applying statistical models with small number of diagnostic tests and sample sizes, proposing design guidelines of future schistosomiasis diagnostic accuracy studies with recommendations for further research. While our study is centred around the diagnosis of schistosomiasis, we feel that the recommendations can be adapted to other major tropical infectious diseases as well.

Background This paper reports on the baseline prevalence and associated risk factor findings of a pilot, longitudinal study exploring community-wide treatment of schistosomiasis and soil-transmitted helminthiasis, using albendazole plus praziquantel in the Greater Accra region of Ghana. Method From three communities, at least, 658 individuals were enrolled into the study via random household selection. Prevalence and intensity of schistosomiasis and STH infection were determined from stool and urine samples with a questionnaire being administered in order to explore other morbidities and risk factors. Factor analysis of household demographic variables was undertaken to generate a socioeconomic score; this was then further categorised into tertiles. Proportional-odds cumulative logit generalised estimating equation (GEE) models were used to investigate categorical ordinal intensity of infection associations with morbidity. Separately, logistic GEE models were used to investigate risk factor associations with infection prevalence. Results Both Schistosoma haematobium and S. mansoni were prevalent in the three communities, with the prevalence of S. haematobium ranging from 3.3% (24/679; 95% CI = 1.9–4.7) to 19% (114/632; 95% CI = 15.8–22.2) and S. mansoni ranging from 30% (202/679; 95% CI = 26.5–33.5) to 78.3% (409/536; 95% CI = 74.7–81.9). The total prevalence of STH across all three sites was negligible at 1.3% (24/1847; 95% CI = 0.8–1.9) comprising mainly hookworm (10/1847). Multivariable statistical models indicated males to be 2.3 (95% CI = 1.7–3.3) times more likely to have a high intensity S. mansoni infection and 1.5 (95% CI = 1.1–2) times more likely to have a high intensity of S. haematobium infection compared to females. There was no significant difference in the likelihood of infection with S. mansoni between adults and school age children (SAC), however S. haematobium infections were found to be 2.5 (95% CI = 1.8–3.5) times more likely to occur in school age children than in adults. Multivariable statistical models (adjusted for age and sex) indicated an association between schistosomiasis and a number of self-reported morbidity indicators (notably diarrhoea and blood in stool and urine). Low socio-economic status was also associated with SCH infection (OR: 2; 95% CI = 1.3–3.2). Conclusion The communities targeted by this study showed a range of Schistosoma prevalence’s of infection, from hypo-endemic through to meso-endemic and hyper-endemic. The prevalence of SCH across the different age groups in the study locations highlights the large number of individuals currently being left out of the standard morbidity control method of annual treatment of the SAC., Author summary In this manuscript we detail the baseline results of a broader study investigating the feasibility of expanding access of albendazole and praziquantel to additional at-risk groups in three communities (Tomefa, Maheam and Torgahkope-Adakope) located around the Weija reservoir in the Greater Accra district of Ghana. Our results show that intestinal schistosomiasis was the most common form of disease across all three sites (44.2%) with Tomefa possessing the highest prevalence at 78.3%. The prevalence of urinary schistosomiasis was found to be 11.9% with the highest prevalence found in Torgahkope-Adakope (19%). STH was found to have a very low prevalence across the three communities with only 1.3% of participants found to be positive. No significant difference in STH prevalence was observed between males (0.92%; 95% CI = 0.4–1.81) and females (1.07%; 95% CI = 0.51–1.95). Statistical analysis revealed that males were more likely to be infected and to have high intensity infections of both forms of schistosomiasis. Pre-school age children (PSAC) were found to be less likely to be infected for either form of schistosomiasis in communities with low to medium prevalence of disease, however in Tomefa, where prevalence of intestinal schistosomiasis is high, there was little difference in the prevalence of disease between PSAC, school-age children (SAC) and adults. Our study shows that there is a need to treat the wider community outside of the current morbidity control strategy of mass-drug administration to SAC.

(1) Background: Current international policy for schistosomiasis and soil-transmitted helminthiasis (STH) control emphasises mass administration of deworming drugs in school-based programmes. However, this approach is insufficient to control the transmission of these diseases, and their burden in non-school cohorts is recognised, albeit under-researched. This research will investigate the feasibility and acceptability of expanding access to praziquantel (PZQ) against schistosomiasis, and albendazole (ALB) against STH, to communities in selected transmission settings in Ghana. (2) Methods: A three-site longitudinal study will be implemented to investigate the effectiveness of expanding treatment strategies for PZQ and ALB to community members. In the context of community mass drug administration (to preschool children, school non-attending children, and adults, including pregnant women), the intervention will be assessed in a random sample of community members, at baseline with follow-up at 6, 12, and 18 months. In each community, 658 participants will be enrolled, and 314 followed up at each time point. The primary outcome measure is the prevalence of infection of Schistosoma haematobium and/or S. mansoni at study endpoint, as assessed by longitudinal surveys. Secondary outcomes are to quantify the infection of schistosomiasis and STH infections in non-treated cohorts, reductions in prevalence of STH, and intensity of schistosomiasis and STH, and treatment coverage. Nested within this study will be qualitative, cost-benefit, and cost-effectiveness evaluations that will explore accessibility, feasibility, and economic impact of expanded treatment from different complementary perspectives. (3) Discussion: Using a multidisciplinary approach, this study will generate evidence for improved availability, acceptability, affordability, and accessibility to deworming drugs against schistosomiasis and STH to individuals and communities in Ghana. This is likely to have considerable research, programmatic, and political value to contribute evidence for national programme policy development within Ghana, and, more broadly, World Health Organization policy development.

Two schistosome species--Schistosoma haematobium and S. mansoni--with two very different pathological profiles (urogenital versus intestinal), are responsible for the majority of human schistosomiasis infections across sub-Saharan Africa. The aim of this study was to determine whether coinfections have an impact on species-specific morbidity measures when compared to single species infections. Children from two neighbouring schools in Taveta, Kenya were grouped by infection status, i.e. uninfected, single species infections or coinfected. Clinical examination of the liver and spleen by palpation was performed and urinary albumin levels were recorded at baseline and at 12 months after praziquantel administration. Additional ultrasonographic profiles of the children's liver, spleen and bladder were incorporated at follow-up. It was found that S. haematobium-associated urogenital morbidity was lower in the coinfected group relative to single S. haematobium infections, even when infection intensities were taken into account. We also observed an association between S. haematobium infection and liver (intestinal-associated) morbidity regardless of coinfections. The findings reported here suggest that further research should be performed on the impact of S. haematobium infections on liver morbidity as well as to determine the impact of mixed schistosome species infections on human morbidity outcomes across different endemic settings.

BackgroundUrine 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.MethodsIn 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.ResultsThe 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).ConclusionAll 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.

Substantial uncertainties surround the sensitivities and specificities of diagnostic techniques for urinary schistosomiasis. We used latent class (LC) modeling to address this problem. In this study, 220 adults in three villages northwest of Accra, Ghana were examined using five Schistosoma haematobium diagnostic measures: microscopic examination of urine for detection of S. haematobium eggs, dipsticks for detection of hematuria, tests for circulating antigens, antibody tests, and ultrasound scans of the urinary system. Testing of the LC model indicated non-invariance of the performance of the diagnostic tests across different age groups, and measurement invariance held for males and females and for the three villages. We therefore recommend the use of LC models for comparison between and the identification of the most accurate schistosomiasis diagnostic tests. Furthermore, microscopy and hematuria dipsticks were indicated through these models as the most appropriate techniques for detection of S. haematobium infection.

Background Diagnosis of urogenital schistosomiasis in chronically infected adults is challenging but important, especially because long term infection of the bladder and urinary tract can have dire consequences. We evaluated three tests for viable infection: detection of parasite specific DNA Dra1 fragments, haematuria and presence of parasite eggs for sensitivity (Se) and specificity (Sp). Methods Over 400 urine specimens collected from adult volunteers in an endemic area in Western Nigeria were assessed for haematuria then filtered in the field, the filter papers dried and later examined for eggs and DNA. The results were stratified according to sex and age and subjected to Latent Class analysis. Conclusions Presence of Dra1 in males (Se = 100%; Sp = 100%) exceeded haematuria (Se = 87.6%: Sp = 34.7%) and detection of eggs (Se = 70.1%; Sp = 100%). In females presence of Dra1 was Se = 100%: Sp = 100%, exceeding haematuria (Se = 86.7%: Sp = 77.0%) and eggs (Se = 70.1%; Sp = 100%). Dra1 became undetectable 2 weeks after praziquantel treatment. We conclude detection of Dra1 fragment is a definitive test for the presence of Schistosoma haematobium infection., Author Summary The definitive test for schistosomiasis has been to detect parasite eggs in excreta. This is effective in children but as people age, it is difficult to find the eggs in spite of suspicion of infection. It also implies that adults have thrown off the infection, and therefore the infection is mainly one of children. However this is not the case as adults with chronic infections can develop severe bladder infection that can progress to bladder cancer. In clinical situations a sensitive test for urogenital schistosomiasis is important. We have recently shown that it is possible to detect schistosome species-specific DNA in urine, even in the absence of eggs in excreta. Here we use latent class analysis to compare sensitivity and specificity of three test procedures, haematuria, eggs in urine and specific DNA in urine in the absence of a gold standard. We show that the latter test is extremely promising for the diagnosis of urogenital schistosomiasis and should also be useful in field studies as it will be able to reveal infections in people frequently presumed to be uninfected. This new test indicated the presence of schistosomes in 10.7% of adults who did not pass eggs in urine specimens.

Background Over 1 billion of the world's poorest inhabitants are afflicted by neglected tropical diseases (NTDs). Integrated control programmes aimed at tackling these debilitating NTDs have been recently initiated, mainly using preventative chemotherapy. Monitoring and evaluation (M&E) of these integrated programs presents particular challenges over and above those required for single disease vertical programmes. We used baseline data from the National NTD Control Programme in Burkina Faso in order to assess the feasibility of an integrated survey design, as well as to elucidate the contribution of environmental variables to the risk of either Schistosoma haematobium, trachoma, or both among school-aged children. Methods S. haematobium infection was diagnosed by detecting eggs in urine. A trachoma case was defined by the presence of Trachomatous inflammation-Follicular (TF) and/or Trachomatous inflammation-Intense (TI) in either eye. Baseline data collected from 3,324 children aged 7-11 years in 21 sentinel sites across 11 regions of Burkina Faso were analyzed using simple and multivariable hierarchical binomial logistic regression models fitted by Markov Chain Monte Carlo estimation methods. Probabilities of the risk of belonging to each infection/disease category were estimated as a function of age, gender (individual level), and environmental variables (at sentinel site level, interpolated from national meteorological stations). Results Overall prevalence at the sentinel sites was 11.79% (95% CI: 10.70-12.89) for S. haematobium; 13.30% (12.14-14.45) for trachoma and 0.84% (0.53-1.15) for co-infections. The only significant predictor of S. haematobium infection was altitude. There were significant negative associations between the prevalence of active trachoma signs and minimum temperature, and air pressure. Conditional upon these predictors, these data are consistent with the two pathogens being independent. Conclusions Urogenital schistosomiasis and trachoma constitute public health problems in Burkina Faso. Sentinel site (at school level) surveys for these two NTDs can be implemented simultaneously. However, to support MDA treatment decisions in Burkina Faso, the protocol used in this study would only be applicable to hypoendemic trachoma areas. More research is needed to confirm if these findings can be generalized to West Africa and beyond.

Background In the developing world co-infections and polyparasitism within humans appear to be the rule rather than the exception, be it any combination of inter-specific and/or inter- and intra-Genera mixed infections. Mixed infections might generate synergistic or antagonistic interactions and thereby clinically affect individuals and/or impact parasite epidemiology. Methods The current study uniquely assesses both Schistosoma mansoni- and Schistosoma haematobium-related morbidity of the liver and the bladder as assessed by ultrasound as well as spleen and liver morbidity through clinical exams. The impact of praziquantel (PZQ) treatment on such potential inter-specific schistosome interactions and resulting morbidity using uniquely detailed longitudinal data (pre- and one year post-PZQ treatment) arising from the National Schistosomiasis Control Program in three areas of Mali: Ségou, Koulikoro and Bamako, is also evaluated. At baseline, data were collected from up to 2196 children (aged 7-14 years), 844 of which were infected with S. haematobium only, 124 with S. mansoni only and 477 with both. Follow-up data were collected from up to 1265 children. Results Results suggested lower liver morbidity in mixed compared to single S. mansoni infections and higher bladder morbidity in mixed compared to single S. haematobium infections. Single S. haematobium or S. mansoni infections were also associated with liver and spleen morbidity whilst only single S. haematobium infections were associated with bladder morbidity in these children (light S. haematobium infection OR: 4.3, p < 0.001 and heavy S. haematobium infection OR: 19, p < 0.001). PZQ treatment contributed to the regression of some of the forms of such morbidities. Conclusions Whilst the precise biological mechanisms for these observations remain to be ascertained, the results illustrate the importance of considering mixed species infections in any analyses of parasite-induced morbidity, including that for the proposed Disability Adjusted Life Years (DALYs) revised estimates of schistosomiasis morbidity.

AIM: To study impact of once weekly iron supplementation on praziquantel cure rate, Schistosoma haematobium reinfection, and haematological parameters in pupils aged between 9 and 15 years of age in Nchelenge district, Zambia. METHODS: Pupils in the intervention group received once weekly dose of ferrous sulphate at 200 mg while those in the control received once weekly vitamin C at 100 mg for up to 9 months. Both study groups received a single dose of praziquantel at baseline. RESULTS: S haematobium reinfection intensity was significantly lower in boys in the intervention group than in boys in the control group at 6 months (P < 0.001) and 9 months (P < 0.001) of supplementation. Significantly lower S haematobium reinfection intensity was found in girls in the intervention group than in girls in the control group only at 6 months of supplementation (P = 0.018). Boys in the intervention group were 42% (Adjusted Risk Ratio = 0.58, 95% confidence interval 0.39, 0.86) less likely to be reinfected with S haematobium than in the control group at 6 months follow up. CONCLUSION: Once weekly iron supplementation can decrease S haematobium reinfection after 6 months and should be incorporated into school based schistosomiasis control programs in highly endemic areas.

Substantial uncertainties surround the sensitivities and specificities of diagnostic techniques for urinary schistosomiasis. We used Latent Class (LC) modeling to address this problem. In this study 220 adults in three villages northwest of Accra in Ghana were examined using five Schistosoma haematobium diagnostic measures: microscopic examination of urine for detection of S. haematobium eggs, dipsticks for detection of haematuria, tests for circulating antigens, serological antibody tests and ultrasound scans of the urinary system. Testing of the LC model indicated non-invariance of the performance of the diagnostic tests across different age groups while measurement invariance held for males and females and for the three villages. We therefore recommend the use of LC models for comparison between, and the identification of, the most accurate schistosomiasis diagnostic tests. Furthermore, microscopy and haematuria dipsticks were indicated through these models as the most appropriate techniques for detection of S. haematobium infection.

Background. In sub-Saharan Africa, 112 million people are infected with Schistosoma haematobium, with the most intense infections in children 5–15 years old. Methods. We describe a longitudinal epidemiological study that evaluates the relationship between S. haematobium infection and associated morbidity in children before and after the large-scale administration of praziquantel for schistosomiasis and albendazole for soil-transmitted helminths. Results. At baseline, higher intensities of S. haematobium infection were observed in children with anemia and/or severe microhematuria, but there was no apparent association between the risk of undernutrition and intensity of S. haematobium infection. Significant reductions in the prevalence and intensity of S. haematobium infection 1 year after treatment were, however, observed. Children who benefited the most from anthelmintic treatment in terms of increased hemoglobin concentrations were those who had anemia at baseline and those with highly positive microhematuria scores at baseline. Conclusions. This study suggests that even a single round of mass chemotherapy can have a substantial impact on S. haematobium infection and its associated morbidity in children.

Objective To evaluate the impact on schistosomiasis of biennial treatment with praziquantel (PZQ) among school-age children in Burkina Faso, the first country that achieved full national coverage with treatment of more than 90% of the school-age population. Methods A cohort of 1727 schoolchildren (6–14 years old) was monitored at yearly intervals through a longitudinal survey. Additional groups of schoolchildren were monitored in cross-sectional surveys. Parasitological examinations for Schistosoma haematobium and Schistosoma mansoni were performed, and prevalence and intensity of infection before and after treatment were analysed. Findings Data from the longitudinal cohort show that a single round of PZQ treatment significantly reduced prevalence of S. haematobium infection by 87% (from 59.6% to 7.7%) and intensity of infection by 92.8% (from 94.2 to 6.8 eggs/10 ml of urine) 2 years posttreatment. The impact on infection was also confirmed by a cross-sectional survey 2 years post-treatment. Importantly, the proportion of school-age children with heavy S. haematobium infection decreased from around 25% before treatment to around 2–3% 2 years post-treatment. Cross-sectional comparison of S. haematobium infection in 7-year-old children in their first year at school, who received treatment through community-based drug delivery, also showed significant reduction in both prevalence (65.9%) and intensity of S. haematobium infection (78.4%) 2 years after single treatment. A significant reduction in S. mansoni infection was also achieved. Conclusion Significant and sustained reduction in S. haematobium infection was achieved by biennial treatment in school-age children in Burkina Faso. This may provide a cost-effective treatment strategy for similar national schistosomiasis control programmes in sub-Saharan Africa. Bulletin of the World Health Organization 2008;86:780–787.