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Background Health related quality of life measurements are vital elements of public health surveillance that uncover unmet health needs and predict the success of health interventions. We described health related quality of life measurements using the EuroQoL 5-dimension (EQ-VAS/EQ-5D) instrument and associated factors among patients with upper gastrointestinal bleeding (UGIB) and hepatic schistosomiasis at a rural health facility in the Albert Nile Basin, Uganda. Methods and materials This was a cross-sectional study at Pakwach Health Centre IV. Participants included adult inpatients and outpatients with a history of UGIB and ultrasound evidence of hepatic schistosomiasis. We evaluated and recorded each participant’s medical history, physical examination, laboratory tests results, ultrasound results, and endoscopy findings. We also recorded health related quality of life measurements using the EuroQoL 5-dimension instrument and derived disability weights from EQ-VAS and EQ-5D measurements. These were our dependent variables. Descriptive and inferential statistics were generated summarizing our findings. Results We found 103 participants had a history of upper gastrointestinal bleeding and hepatosplenic schistosomiasis. Sixty percent were between the ages of 30–49 years, 59% were females, 74% were farmers, 92% had splenomegaly, 88% had varices at endoscopy, 22% were medical emergencies with acute variceal upper gastrointestinal bleeding, and 62% had anemia. Measures of the different dimensions of health from 101 participants with patient reported outcomes revealed 77 (76%) participants experienced problems in self-care, 89 (88%) participants reported anxiety or depression, and 89 (88%) participants experienced pain or discomfort. The median EQ-VAS derived disability weights and median EQ-5D index-derived disability weights were 0.3 and 0.34, respectively. Acute upper gastrointestinal bleeding, praziquantel drug treatment, and age by decade predicted higher EQ-VAS derived disability weights (p value p value Conclusion Adult patients with upper gastrointestinal bleeding and hepatic schistosomiasis from this primary health facility experience poor health and considerable health loss. Several factors predicted increased health loss. These factors probably represent key areas of health intervention towards mitigating increased health loss in this population.

Control and elimination of the parasitic disease schistosomiasis relies on mass administration of praziquantel. Whilst these programmes reduce infection prevalence and intensity, their impact on parasite transmission and evolution is poorly understood. Here we examine the genomic impact of repeated mass drug administration on Schistosoma mansoni populations with documented reduced praziquantel efficacy. We sequenced whole-genomes of 198 S. mansoni larvae from 34 Ugandan children from regions with contrasting praziquantel exposure. Parasites infecting children from Lake Victoria, a transmission hotspot, form a diverse panmictic population. A single round of treatment did not reduce this diversity with no apparent population contraction caused by long-term praziquantel use. We find evidence of positive selection acting on members of gene families previously implicated in praziquantel action, but detect no high frequency functionally impactful variants. As efforts to eliminate schistosomiasis intensify, our study provides a foundation for genomic surveillance of this major human parasite., Schistosomiasis control strategies rely on mass drug administration (MDA) using praziquantel. Here, Berger et al. perform whole-genome sequencing of larvae from infected children across Ugandan regions with differing MDA histories. They find extensive gene flow with limited positive selection suggesting minimal change post MDA.

Background There is a general consensus that widespread use of praziquantel in populations where schistosomiasis is endemic prevents development of hepatic schistosomiasis and its complications. However, a few studies have reported discordant findings linking praziquantel to the occurrence of upper gastrointestinal bleeding (UGIB) in some patients with hepatic schistosomiasis and varices. Objective We explored if there was any causal association between recent praziquantel use (rPZQ) and upper gastrointestinal bleeding in hepatic schistosomiasis in rural Africa. Patients and Methods A quasi-experimental, retrospective case-controlled study was performed. It involved adult patients with past or acute UGIB, varices, periportal fibrosis, and/or cirrhosis. Cases had acute variceal bleeding while controls did not. The outcome was the frequency of lifetime episodes of UGIB and exposure was rPZQ (received praziquantel in the last 11 months from the date of enrollment). The data analysis included 2 × 2 tables, logistic regression, and propensity-score matching. Odds ratios (ORs), average treatment effects (ATEs), and their 95% confidence intervals (CIs) were used for inference. Results Over 6 weeks, we enrolled 19 cases with 92 lifetime episodes of UGIB, and 66 controls with 192 lifetime episodes of UGIB. Cases were more likely to experience UGIB than controls following rPZQ (92% vs. 62%; OR 7.6; 95% CI 3.4–17). Factors predictive of more lifetime episodes of UGIB at multivariable analysis included rPZQ (adjusted OR 13; 95% CI 2.9–53), relative leukocytosis (adjusted OR 26; 95% CI 7.6–89), large varices (adjusted OR 5.0; 95% CI 1.7–15), a family member with hepatosplenic schistosomiasis (adjusted OR 19; 95% CI 7.4–51), advanced periportal fibrosis (adjusted OR 8.0; 95% CI 2.6–22), ascites (adjusted OR 14; 95% CI 4.3–47), and jaundice (adjusted OR 32; 95% CI 7.8–128). While the ATE following rPZQ among the treated was 0.40 (95% CI 0.33–0.48). Conclusions Our findings suggest the presence of a plausible causal association between recent praziquantel use and increased frequency of UGIB in our study population. Supplementary Information The online version contains supplementary material available at 10.1007/s40801-020-00222-7.

Malaria–schistosomiasis coinfections are common in sub-Saharan Africa but studies present equivocal results regarding the interspecific relationships between these parasites. Through mixed-model analyses of a dataset of Ugandan preschool children, we explore how current coinfection and prior infection with either Schistosoma mansoni or Plasmodium species alter subsequent Plasmodium intensity, Plasmodium risk, and S mansoni risk. Coinfection and prior infections with S mansoni were associated with reduced Plasmodium intensity, moderated by prior Plasmodium infections, wealth, and host age. Future work should assess whether these interactions impact host health and parasite control efficacy in this vulnerable age group.

Background The interaction of socio-demographic and ecological factors with Schistosoma mansoni (S. mansoni) infection risk by age and the household clustering of infections between individuals are poorly understood. Methods This study examined 1,832 individuals aged 5–90 years across 916 households in Mayuge District, Uganda. S. mansoni infection status and intensity were measured using Kato-Katz microscopy. Socio-demographic and ecological factors were examined as predictors of infection status and intensity using logistic and negative binomial regression models, respectively, with standard errors clustered by household. A subgroup analysis of children was conducted to examine the correlation of infection status between children and their caretakers. Findings Infection varied within age groups based on the distance to Lake Victoria. Children aged 9–17 years and young adults aged 18–29 years who lived ≤0.50km from Lake Victoria were more likely to be infected compared to individuals of the same age who lived further away from the lake. Infections clustered within households. Children whose caretakers were heavily infected were 2.67 times more likely to be infected. Conclusion These findings demonstrate the focality of schistosome transmission and its dependence on socio-demographic, ecological and household factors. Future research should investigate the sampling of households within communities as a means of progressing towards precision mapping of S. mansoni infections.

Background Over 200 million individuals worldwide are infected with Schistosoma species, with over half of infections occurring in children. Many children experience first infections early in life and this impacts their growth and development; however praziquantel (PZQ), the drug used worldwide for the treatment of schistosomiasis, only has regulatory approval among adults and children over the age of four, although it is frequently used “off label” in endemic settings. Furthermore, pharmacokinetic/pharmacodynamics (PK/PD) evidence suggests the standard PZQ dose of 40 mg/kg is insufficient in preschool-aged children (PSAC). Our goal is to understand the best approaches to optimising the treatment of PSAC with intestinal schistosomiasis. Methods We will conduct a randomised, controlled phase II trial in a Schistosoma mansoni endemic region of Uganda and a Schistosoma japonicum endemic region of the Philippines. Six hundred children, 300 in each setting, aged 12–47 months with Schistosoma infection will be randomised in a 1:1:1:1 ratio to receive either (1) 40 mg/kg PZQ at baseline and placebo at 6 months, (2) 40 mg/kg PZQ at baseline and 40 mg/kg PZQ at 6 months, (3) 80 mg/kg PZQ at baseline and placebo at 6 months, or (4) 80 mg/kg PZQ at baseline and 80 mg/kg PZQ at 6 months. Following baseline treatment, children will be followed up for 12 months. The co-primary outcomes will be cure rate and egg reduction rate at 4 weeks. Secondary outcomes include drug efficacy assessed by novel antigenic endpoints at 4 weeks, actively collected adverse events and toxicity for 12 h post-treatment, morbidity and nutritional outcomes at 6 and 12 months, biomarkers of inflammation and environmental enteropathy and PZQ PK/PD parameters. Discussion The trial will provide valuable information on the safety and efficacy of the 80 mg/kg PZQ dose in PSAC, and on the impact of six-monthly versus annual treatment, in this vulnerable age group. Trial registration ClinicalTrials.gov NCT03640377. Registered on 21 Aug 2018.

Introduction Health related quality of life (HRQOL) measurements, which include disability weights, are important endpoints of health care delivery. These measurements are scarce for patients with upper gastrointestinal bleeding (UGIB) in rural sub-Saharan Africa (SSA) where schistosomiasis is endemic. Methods and materials In 2014, we studied HRQOL measurements among patients with UGIB in SSA where schistosomiasis is endemic. Participants included adult inpatients and outpatients with a history of UGIB at a primary health facility. We measured HRQOL using the EuroQoL 5-dimension (EQ-VAS/EQ5D) instrument and derived disability weights from EQ-VAS and EQ5D measurements. We profiled each participant’s medical history, physical examination, laboratory tests, imaging, and endoscopy findings. These were summarized through descriptive and inferential statistics.Results We studied 107 participants with a median age of 45 years. All participants experienced ≥1 lifetime episode of UGIB, 60% were females, while 22% had acute severe UGIB requiring admission, 98% hepatic schistosomiasis, 90% splenomegaly, 80% had esophageal varices, and 20% had peptic ulcers. Most (80%) had ever received praziquantel for schistosomiasis. No participant had ever had an endoscopy for UGIB or received propranolol for prevention of recurrent variceal UGIB. Measures of the 5 dimensions of health revealed a large proportion of participants had problems related to self-care (76%), anxiety/depression (88%), and pain/discomfort (89%). Few participants had problems with mobility(37%). The mean/median EQ-VAS derived disability weights and EQ5D derived disability weights were 0.38/0.30 and 0.38/0.34, respectively. Participants with ascites, acute UGIB, and severe anemia were found to have the highest EQ-VAS and EQ5D median disability weights. At linear regression age, female gender, ascites, and acute UGIB predicted EQ-VAS derived disability weights [F(4,100)=9.35, pConclusions In our study, older age, female gender, those with ascites or acute UGIB had the highest disability weights, and the greatest probability of having higher disability weights among patients with a history of UGIB where schistosomiasis is endemic. These findings are unique and improve the definitions of different health states among patients with UGIB and schistosomiasis.

Background Praziquantel mass drug administration (MDA) is recommended in schistosomiasis-endemic areas. Animal models demonstrate Schistosoma parasite resistance to praziquantel after repeated exposure. Methods We conducted a parasitological survey in 26 fishing communities in Uganda after 4 years of quarterly (13 communities) or annual (13 communities) praziquantel MDA, with Schistosoma infection detected by single-stool-sample Kato-Katz. A test of cure was done in participants who were positive on both urine circulating cathodic antigen test and 3-sample Kato-Katz. We calculated cure rates (CRs) and egg reduction rates (ERRs) based on 3-sample Kato-Katz and infection intensity using worm-specific circulating anodic antigen (CAA) in blood, comparing these between quarterly and annually treated participants. Results Single-sample Kato-Katz Schistosoma mansoni prevalence was 22% in 1,056 quarterly treated participants and 34% in 1,030 annually treated participants (risk ratio, 0.62; 95% confidence interval [CI], 0.40 to 0.94). Among 110 test-of-cure participants, CRs were 65% and 51% in annually and quarterly treated villages, respectively (odds ratio, 0.65; 95% CI, 0.27 to 1.58); ERRs were 94% and 81% (difference, –13%; 95% CI, –48% to 2%). There was no impact of quarterly vs annual praziquantel on S. mansoni by CAA. Conclusions In this schistosomiasis hot spot, there was little evidence of decreased praziquantel efficacy. However, in the absence of alternative therapies, there remains a need for continued vigilance of praziquantel efficacy in the MDA era.

The dataset for this article contains Urinary and Intestinal Schistosomiasis from Lango region, northern Uganda which is the only known co-endemic region for S.mansoni and S.haematobium. Reported in the data, is the retrospective data review for historical information before interventions were implemented before 2003 and after interventions were implemented in 2003 by the national control program. In 2007 and 2011, parasitological surveys were conducted in the region to validate Schistosomiasis trends following World Health Organization (WHO) guidelines for surveys. In addition, malacological surveys were undertaken in 2007 to assess local transmission potential. The dataset can provide an insight into the health implications of Schistosomiasis control in co-endemic focus in Uganda, “The epidemiology of schistosomiasis in Lango region Uganda 60 years after Schwetz 1951: Can schistosomiasis be eliminated through mass drug administration without other supportive control measures?” (Adriko et al., 2018) [10].

Background Despite decades of community-based mass drug administration (MDA) for neglected tropical diseases, it remains an open question as to what constitutes the best combination of community medicine distributors (CMDs) for achieving high (>65%/75%) treatment rates within a village. Methods Routine community-based MDA was evaluated in Mayuge District, Uganda. For one month, we tracked 6,148 individuals aged 1+ years in 1,118 households from 28 villages. Praziquantel, albendazole, and ivermectin were distributed to treat Schistosoma mansoni, lymphatic filariasis, and soil-transmitted helminths. The similarity/diversity between CMDs was observed and used to predict the division of labour and overall village treatment rates. The division of labour was calculated by dividing the lowest treatment rate by the highest treatment rate achieved by two CMDs within a village. CMD similarity was measured for 16 characteristics including friendship network overlap, demographic and socioeconomic factors, methods of CMD selection, and years as CMD. Relevant variables for MDA outcomes were selected through least absolute shrinkage and selection operators with leave-one-out cross validation. Final models were run with ordinary least squares regression and robust standard errors. Results The percentage of individuals treated with at least one drug varied across villages from 2.79–89.74%. The only significant predictor (p-value, Author summary Community-based mass drug administration (MDA) uses volunteers within at-risk communities to distribute preventive chemotherapies en masse for neglected tropical diseases. Treatment rates achieved by community medicine distributors (CMDs) vary widely and can undermine morbidity control. We studied routine community-based MDA in 28 villages near Lake Victoria in Uganda. There were two CMDs per village who were tasked with moving from home-to-home to administer praziquantel, albendazole, and ivermectin for schistosomiasis, lymphatic filariasis, and soil-transmitted helminths. We observed treatment outcomes for 6,148 eligible individuals aged 1+ years. Here we identified the best combination of CMD characteristics for achieving high village-level treatment rates. We found that a more equal division of labour (e.g. 50–50 split between how many people each CMD treated) was associated with higher treatment rates when compared to CMDs with an unequal division of labour (e.g. one CMD treating no one). CMDs who were friends were more likely to have a division of labour that was nearly twofold more equal than CMDs who were not friends. The similarity of CMDs with respect to network, demographic, or socioeconomic characteristics did not influence village treatment rates. National programmes should explore interventions that seek to facilitate communication, friendship, and equal partnership between CMDs.

Schistosomiasis is a parasitic infection highly prevalent in sub-Saharan Africa, and a significant cause of morbidity; it is a priority for vaccine development. A controlled human infection model for Schistosoma mansoni (CHI-S) with potential to accelerate vaccine development has been developed among naïve volunteers in the Netherlands. Because responses both to infections and candidate vaccines are likely to differ between endemic and non-endemic settings, we propose to establish a CHI-S in Uganda where Schistosoma mansoni is endemic. As part of a “road-map” to this goal, we have undertaken a risk assessment. We identified risks related to importing of laboratory vector snails and schistosome strains from the Netherlands to Uganda; exposure to natural infection in endemic settings concurrently with CHI-S studies, and unfamiliarity of the community with the nature, risks and rationale for CHI. Mitigating strategies are proposed. With careful implementation of the latter, we believe that CHI-S can be implemented safely in Uganda. Our reflections are presented here to promote feedback and discussion.

Controlled human infection (CHI) models are gaining recognition as an approach to accelerating vaccine development, for use in both non-endemic and endemic populations: they can facilitate identification of the most promising candidate vaccines for further trials and advance understanding of protective immunity. Helminths present a continuing health burden in sub-Saharan Africa. Vaccine development for these complex organisms is particularly challenging, partly because protective responses are akin to mechanisms of allergy. A CHI model for Schistosoma mansoni (CHI-S) has been developed at Leiden University Medical Centre, the Netherlands. However, responses to schistosome infections, and candidate vaccines, are likely to be different among people from endemic settings compared to schistosome-naïve Dutch volunteers. Furthermore, among volunteers from endemic regions who have acquired immune responses through prior exposure, schistosome challenge can be used to define responses associated with clinical protection, and thus to guide vaccine development. To explore the possibility of establishing the CHI-S in Uganda, a Stakeholders’ Meeting was held in Entebbe in 2017. Regulators, community members, researchers and policy-makers discussed implementation challenges and recommended preparatory steps: risk assessment; development of infrastructure and technical capacity to produce the infectious challenge material in Uganda; community engagement from Parliamentary to grass-roots level; pilot studies to establish approaches to assuring fully informed consent and true voluntariness, and strategies for selection of volunteers who can avoid natural infection during the 12-week CHI-S; the building of regulatory capacity; and the development of study protocols and a product dossier in close consultation with ethical and regulatory partners. It was recommended that, on completion, the protocol and product dossier be reviewed for approval in a joint meeting combining ethical, regulatory and environment management authorities. Most importantly, representatives of schistosomiasis-affected communities emphasised the urgent need for an effective vaccine and urged the research community not to delay in the development process.

Background As part of ongoing co-surveillance of intestinal schistosomiasis and malaria in Ugandan school children, a non-invasive detection method for amplification of Plasmodium DNA using real-time (rt)PCR analysis of ethanol preserved faeces (EPF) was assessed. For diagnostic tabulations, results were compared to rtPCR analysis of dried blood spots (DBS) and field-based point-of-care (POC) rapid diagnostic tests (RDTs). Methods A total of 247 school children from 5 primary schools along the shoreline of Lake Albert were examined with matched EPF and DBS obtained. Mean prevalence and prevalence by school was calculated by detection of Plasmodium DNA by rtPCR using a 18S rDNA Taqman® probe. Diagnostic sensitivity, specificity, positive and negative predictive values were tabulated and compared against RDTs. Results By rtPCR of EPF and DBS, 158 (63.9%; 95% CI 57.8–69.7) and 198 (80.1%, 95% CI 74.7–84.6) children were positive for Plasmodium spp. By RDT, 138 (55.8%; 95% CI 49.6–61.9) and 45 (18.2%; 95% CI 13.9–23.5) children were positive for Plasmodium falciparum, and with non-P. falciparum co-infections, respectively. Using RDT results as a convenient field-based reference, the sensitivity of rtPCR of EPF and DBS was 73.1% (95% CI 65.2–79.8) and 94.2% (95% CI 88.9–97.0) while specificity was 47.7% (95% CI 38.5–57.0) and 37.6% (95% CI 29.0–46.9), respectively. With one exception, school prevalence estimated by analysis of EPF was higher than that by RDT. Positive and negative predictive values were compared and discussed. Conclusions In this high transmission setting, EPF sampling with rtPCR analysis has satisfactory diagnostic performance in estimation of mean prevalence and prevalence by school upon direct comparison with POC-RDTs. Although analysis of EPF was judged inferior to that of DBS, it permits an alternative non-invasive sampling regime that could be implemented alongside general monitoring and surveillance for other faecal parasites. EPF analysis may also have future value in passive surveillance of low transmission settings.

Background Mass drug administration (MDA) is a cornerstone of control of parasitic helminths. In schistosomiasis-endemic areas with >50% of school-aged children infected, community-wide MDA with praziquantel is recommended by the World Health Organisation (WHO), with target coverage of >75%. Using data from a cluster-randomised trial of MDA treatment strategies, we aimed to describe the proportion of eligible residents who received MDA and predictors of treatment receipt, and to assess associations with helminth prevalence. Methods In the Koome islands of Lake Victoria, Uganda, where baseline schistosomiasis prevalence (by single stool sample, Kato Katz) was 52% overall (all ages) and 67% among school-aged children, we conducted a cluster-randomised trial of community-wide, intensive MDA (quarterly single-dose praziquantel 40mg/kg; triple-dose albendazole 400mg) versus standard, Uganda government intervention (annual single-dose praziquantel 40mg/kg; 6-monthly single-dose albendazole). Twenty-six fishing villages were randomised, 13 per trial arm, for four years. At each treatment round, praziquantel treatment and the first dose of albendazole treatment were directly observed by the study team, registers of village residents were updated and the proportion receiving treatment among those eligible recorded. Results During the four-year MDA, at each treatment round an average of 13,382 people were registered in the 26 villages (7,153 and 6,229 in standard and intensive intervention villages, respectively). Overall, the proportion of those eligible receiving praziquantel was lower than for albendazole (60% versus 65%), particularly in the standard arm (61% versus 71%) compared to the intensive arm (60% versus 62%). Albendazole receipt was lower when given concurrently with praziquantel. Absence was the commonest reason for non-receipt of treatment (81% albendazole, 77% praziquantel), followed by refusal (14% albendazole, 18% praziquantel). Proportions receiving treatment were lowest among school-aged children, but did not differ by sex. Longitudinal analysis of a subgroup of residents who did not move during the study period found that persistent non-receipt of treatment in this subgroup was rare. Refusal to receive treatment was highest among adults and more common among females. Conclusion In schistosomiasis high-risk communities, a combination of approaches to increasing treatment coverage, such as extended periods of treatment delivery, and the provision of incentives, may be required to achieve WHO targets., Author summary Mass de-worming is recommended by the World Health Organisation in communities with a heavy burden of worms, but coverage can be sub-optimal. We used data from a four-year long cluster randomised controlled trial conducted in a heavy worm burden area on Lake Victoria, Uganda, to investigate coverage of community-delivered albendazole and praziquantel treatment. We also investigated which factors were associated with receipt of treatment and with refusal. We found that, on average, a lower proportion of residents received praziquantel than albendazole, and that absence and refusal were the most common reasons for not receiving treatment. In the absence of adequate provision of water and sanitation, or of an effective vaccine, innovative approaches to increasing treatment coverage are likely to be needed to substantially reduce worm prevalence.

Schistosomiasis affects over 200 million people worldwide [1] and accounts for an estimated 1.9 million disability-adjusted life years (DALYs) annually [2], with 90% of the burden currently concentrated in Africa. The last decade has witnessed an extraordinary surge of advocacy and funding for neglected tropical diseases (NTDs), including schistosomiasis. Large-scale schistosomiasis control is now implemented in 30 countries in Africa [1], funded primarily through support from the United States Agency for International Development (USAID) and the Department for International Development (DFID), private philanthropic funds from the END Fund and through GiveWell recommendations, and leveraging praziquantel donations from Merck KGaA. However, the number of people still requiring treatment remains daunting [1]. The aim of current public health strategies for schistosomiasis is to decrease morbidity through preventive chemotherapy (PC) (Fig 1) [3]. Periodic large-scale administration of the drug praziquantel focusing on the school-aged population and high-risk adults aims to reduce the prevalence and intensity of infection [4].

Background The development of new diagnostics is an important tool in the fight against disease. Latent Class Analysis (LCA) is used to estimate the sensitivity and specificity of tests in the absence of a gold standard. The main field diagnostic for Schistosoma mansoni infection, Kato-Katz (KK), is not very sensitive at low infection intensities. A point-of-care circulating cathodic antigen (CCA) test has been shown to be more sensitive than KK. However, CCA can return an ambiguous ‘trace’ result between ‘positive’ and ‘negative’, and much debate has focused on interpretation of traces results. Methodology/Principle findings We show how LCA can be extended to include ambiguous trace results and analyse S. mansoni studies from both Côte d’Ivoire (CdI) and Uganda. We compare the diagnostic performance of KK and CCA and the observed results by each test to the estimated infection prevalence in the population. Prevalence by KK was higher in CdI (13.4%) than in Uganda (6.1%), but prevalence by CCA was similar between countries, both when trace was assumed to be negative (CCAtn: 11.7% in CdI and 9.7% in Uganda) and positive (CCAtp: 20.1% in CdI and 22.5% in Uganda). The estimated sensitivity of CCA was more consistent between countries than the estimated sensitivity of KK, and estimated infection prevalence did not significantly differ between CdI (20.5%) and Uganda (19.1%). The prevalence by CCA with trace as positive did not differ significantly from estimates of infection prevalence in either country, whereas both KK and CCA with trace as negative significantly underestimated infection prevalence in both countries. Conclusions Incorporation of ambiguous results into an LCA enables the effect of different treatment thresholds to be directly assessed and is applicable in many fields. Our results showed that CCA with trace as positive most accurately estimated infection prevalence., Author summary Schistosomiasis is a debilitating disease affecting over 200 million people worldwide, mainly in developing countries. Treatment for schistosomiasis is straightforward and involves treating all school-age children, and sometimes also adults, in areas where schistosomiasis is known to occur. However, detecting intestinal schistosomiasis (Schistosoma mansoni) using Kato-Katz, the most common technique, can fail to detect infection when it is present as Kato-Katz relies on finding eggs within a small stool sample. A new field diagnostic, CCA, is promising as it is simple to use and seems to detect more infections that Kato-Katz. However, assessing the performance of CCA is difficult as we cannot be certain whether or not those positive by CCA but negative by Kato-Katz are truly infected. Additionally, CCA can often return a trace result between negative and positive which is difficult to interpret. We assess the performance of Kato-Katz and CCA in both Côte d’Ivoire and Uganda. We showed that CCA did indeed detect more infections than Kato-Katz, and that CCA accurately estimated the proportion of people truly infected in the population, when trace readings were considered positive. CCA is consequently an important and valuable tool in the fight against schistosomiasis.

Major control efforts over many decades have resulted in a substantial reduction in the prevalence of schistosomiasis japonica in the People’s Republic of China, although pockets of new infection continue to arise, particularly in the mountainous areas of the south. As well, the completion of the Three Gorges Dam, which crosses the Yangtze River and other large irrigation projects underway, may have significant environmental and ecological impacts likely resulting in expansion of the habitats for the intermediate snail host Oncomelania hupensis in some areas, thereby increasing the risk of human and bovine infection, and resulting in potentially new challenging consequences for control. The epidemiological picture for China will be briefly summarised and the current effective control strategies highlighted. The situation in the Philippines will also be briefly outlined but the picture is far less encouraging as there is limited national funding for schistosomiasis control; since the termination of the World Bank Loan program for schistosomiasis control in the late 1990’s, both schistosome prevalence and the associated morbidity have rebounded to former levels. Some results of recent surveillance studies we have undertaken in the Philippines will be described which indicate that schistosomiasis japonica is now far more prevalent, both in humans and bovines, than has been appreciated. Results of a large intervention trial we have completed in China - in the highly endemic Dongting Lake area downstream of the Three Gorges Dam, aimed at field-testing integrated strategies, including the use of a bovine transmission blocking vaccine, for schistosomiasis control, will be presented. The results of the trial in China will provide parameters for mathematical modelling of future control methods so as to define the long-term impact and cost-effectiveness of integrated control measures for both China and the Philippines. We believe that such an integrated approach, incorporating bovine vaccination, can lead to the future elimination of schistosomiasis from China.

This study documented the population dynamics ofBiomphalariaand associated natural infections with digenetic trematodes, along the shores of Lake Albert and Lake Victoria, recording local physicochemical factors. Over a two-and-a-half-year study period with monthly sampling, physicochemical factors were measured at 12 survey sites and all freshwater snails were collected. RetainedBiomphalariawere subsequently monitored in laboratory aquaria for shedding trematode cercariae, which were classified as either human infective (Schistosoma mansoni) or nonhuman infective. The population dynamics ofBiomphalariadiffered by location and by lake and had positive relationship with pH (P<0.001) in both lakes and negative relationship with conductivity (P=0.04) in Lake Albert. Of theBiomphalariacollected in Lake AlbertN=6,183, 8.9% were infected with digenetic trematodes of which 15.8% were sheddingS. mansonicercariae and 84.2% with nonhuman infective cercariae. In Lake Victoria, 2.1% of collectedBiomphalaria N=13,172were infected with digenetic trematodes with 13.9% sheddingS. mansonicercariae, 85.7% shedding nonhuman infective cercariae, and 0.4% of infected snails shedding both types of cercariae. Upon morphological identification, species ofBiomphalariainfected includedB. sudanica,B. pfeifferi, andB. stanleyiin Lake Albert andB. sudanica,B. pfeifferi, andB. choanomphalain Lake Victoria. The study found the physicochemical factors that influencedBiomphalariapopulation and infections. The number and extent of snails sheddingS. mansonicercariae illustrate the high risk of transmission within these lake settings. For better control of this disease, greater effort should be placed on reducing environmental contamination by improvement of local water sanitation and hygiene.

Schistosomiasis control and elimination has priority in public health agendas in several sub-Saharan countries. However, achieving these goals remains a substantial challenge. In order to assess progress of interventions and treatment efficacy it is pertinent to have accurate, feasible and affordable diagnostic tools. Detection of Schistosoma mansoni infection by circulating cathodic antigen (CCA) in urine is an attractive option as this measure describes live worm infection noninvasively. In order to interpret treatment efficacy and re-infection levels, knowledge about clearance of this antigen is necessary. The current study aims to investigate, whether antigen clearance as a proxy for decreasing worm numbers is reflected in decreasing CCA levels in urine shortly after praziquantel treatment. Here CCA levels are measured 24 hours post treatment in response to both a single and two treatments. The study was designed as a series of cross-sectional urine and stool sample collections from 446 individuals nested in a two-arm randomised single blinded longitudinal clinical trial cohort matched by gender and age (ClinicalTrials.gov Identifier: NCT00215267) receiving one or two praziquantel treatments. CCA levels in urine were determined by carbon-conjugated monoclonal antibody lateral flow strip assay and eggs per gram faeces for S. mansoni and soil-transmitted helminths by Kato-Katz. Significant correlations between CCA levels and S. mansoni egg count at every measured time point were found and confirmed the added beneficial effect of a second treatment at two weeks after baseline. Furthermore, presence of hookworm was found not to be a confounder for CCA test specificity. Twenty-four hours post treatment measures of mean CCA scores showed significant reductions. In conclusion, removal of CCA in response to treatment is detectable as a decline in CCA in urine already after 24 hours. This has relevance for use and interpretation of laboratory based and point-of-care CCA tests in terms of treatment efficacy and re-infection proportions as this measure provides information on the presence of all actively feeding stages of S. mansoni, which conventional faecal microscopy methods do not accurately reflect. Trial registration ClinicalTrials.gov NCT00215267, Author summary Large scale efforts to control schistosomiasis in several sub-Saharan countries are in progress. In order to accurately monitor the effect of interventions, we need diagnostic tools which are highly specific, sensitive, affordable and easy to use and implement. For Schistosoma mansoni detection the circulating cathodic antigen (CCA) is an attractive option as this antigen is a measure of actively feeding worms and can be measured in urine samples. However, knowledge about how fast this antigen is cleared in response to treatment with praziquantel is necessary for interpretation of consecutive measures based on CCA in order to use this tool optimally. Here we show that CCA is already significantly reduced 24 hours after treatment both in single and double treatment regimens in a community sample from Musoli Village, Uganda. Furthermore, the data supports interpretation of trace measures of CCA as positive since the majority of individuals with trace measures respond to treatment. These observations provide a basis for extended use of CCA-based tools in monitoring treatment efficacy and possibilities for logistically advantageous prevalence screening strategies.

A longitudinal cohort study of multispecies Plasmodium infections in mothers and children in Uganda has revealed there to be both persistent and increasing parasitemia of certain species, which has clinical significance, despite regular access to frontline antimalarial treatments., As part of a longitudinal cohort investigation of intestinal schistosomiasis and malaria in Ugandan children and their mothers on the shorelines of Lakes Victoria and Albert, we documented risk factors and morbidity associated with nonfalciparum Plasmodium infections and the longitudinal dynamics of Plasmodium species in children. Host age, household location, and Plasmodium falciparum infection were strongly associated with nonfalciparum Plasmodium infections, and Plasmodium malariae infection was associated with splenomegaly. Despite regular artemisinin combination therapy treatment, there was a 3-fold rise in P. malariae prevalence, which was not accountable for by increasing age of the child. Worryingly, our findings reveal the consistent emergence of nonfalciparum infections in children, highlighting the complex dynamics underlying multispecies infections here. Given the growing body of evidence that nonfalciparum malaria infections cause significant morbidity, we encourage better surveillance for nonfalciparum Plasmodium infections, particularly in children, with more sensitive DNA detection methods and improved field-based diagnostics.

SUMMARYPart of Robert T. Leiper's (1881–1969) lasting legacy in medical helminthology is grounded on his pioneering work on schistosomiasis (Bilharzia). Having undertaken many expeditions to the tropics, his fascination with parasite life cycles typically allowed him to devise simple preventive measures that curtailed transmission. Building on his formative work with others in Africa and Asia, and again in Egypt in 1915, he elucidated the life cycles of African schistosomes. His mandate, then commissioned by the British War Office, was to prevent and break transmission of this disease in British troops. This he did by raising standing orders based on simple water hygiene measures. Whilst feasible in military camp settings, today their routine implementation is sadly out of reach for millions of Africans living in poverty. Whilst we celebrate the centenary of Leiper's research we draw attention to some of his lesser known colleagues, then focus on schistosomiasis in Uganda discussing why expanded access to treatment with praziquantel is needed now. Looking to WHO 2020 targets for neglected tropical diseases, we introduce COUNTDOWN, an implementation research consortium funded by DFID, UK, which fosters the scale-up of interventions and confirm the current relevance of Leiper's original research.

Community health interventions often seek to intentionally destroy paths between individuals to prevent the spread of infectious diseases. Immunizing individuals through direct vaccination or the provision of health education prevents pathogen transmission and the propagation of misinformation concerning medical treatments. However, it remains an open question whether network-based strategies should be used in place of conventional field approaches to target individuals for medical treatment in low-income countries. We collected complete friendship and health advice networks in 17 rural villages of Mayuge District, Uganda. Here we show that acquaintance algorithms, i.e., selecting neighbors of randomly selected nodes, were systematically more efficient in fragmenting all networks than targeting well-established community roles, i.e., health workers, village government members, and schoolteachers. Additionally, community roles were not good proxy indicators of physical proximity to other households or connections to many sick people. We also show that acquaintance algorithms were effective in offsetting potential noncompliance with deworming treatments for 16,357 individuals during mass drug administration (MDA). Health advice networks were destroyed more easily than friendship networks. Only an average of 32% of nodes were removed from health advice networks to reduce the percentage of nodes at risk for refusing treatment in MDA to below 25%. Treatment compliance of at least 75% is needed in MDA to control human morbidity attributable to parasitic worms and progress toward elimination. Our findings point toward the potential use of network-based approaches as an alternative to role-based strategies for targeting individuals in rural health interventions.

Background Soil-transmitted Helminths and Anemia potentially reduce and retard cognitive and physical growth in school-age children with great implications for national control programs in Africa. After 13 years of deworming and limited health education campaigns, a study was undertaken to evaluate the impact of deworming interventions on the prevalence and intensity of soil-transmitted helminthic infections in school-age children in Uganda. Methodology A cross-sectional study was carried out in six regions of Uganda, where two districts were randomly selected per region based on the ecological zones in the country. Included in the study were the districts; Mpigi and Nakasongola from the Central; Nakapiripirit and Kotido from Karamoja; Arua and Yumbe from West Nile; Gulu and Alebtong from the North; Kaliro and Mbale from the East; Hoima and Bundibugyo in the West. Five schools were randomly selected from each district and in each school 50 children aged 6–14 years were randomly selected. Stool samples were taken each child and examined for the presence of helminthic infections. A short pretested questionnaire was administered to each participant to obtain their knowledge, attitude, and practice relating to STH infections, their control. General observations were made on environmental sanitation in the schools. The location of each school was geo-referenced using a GPS machine (Garmin®GPSMAP62, Garmin Ltd, Southampton, UK). Results In total, 4,285 children were assessed including 719(16.82%) from central region, 718(16.80%) from eastern region, 719 (16.82%) from northern region, 689 (18.82%) from Karamoja region, 717(16.77%) from West Nile region and 723(16.91%) from western region. The average age of the children was 12.6 years with a standard deviation, SD 1.8 years and the minimum age was 6 years and upper age limit of 12 years. The percentage of boys (50.1%) and girls (49.9%) was comparable. 8.8% (95% CI; 8.0–9.7) were infected with at least any one STH species. Hookworm was the most prevalent (7.7%; 95% CI; 6.9–8.5) followed by whipworms (Trichuris trichiura) (1.3%; 95% CI; 1.0–1.7) and roundworms (Ascaris lumbricoides) (0.5%; 95% CI; 0.3–0.7). Some children had Schistosoma mansoni, 13.0% (95% CI; 12.0–14.0). All the children knew what soil transmitted helminths were (62.8%, 95% CI: 61.3–64.2) and most common knowledge of information were from; home (39%, 95% CI: 37.1–40.8), media (radio& newspaper)(11%, 95% CI: 9.8–12.2), school(65.7%, 95% CI: 63.9–67.5) and friends(11.5%, 95% CI: 10.3–12.7). Majority were aware of how one gets infected with soil transmitted helminths through; eating contaminated food (77.5%, 95% CI: 76.0–79.1), walking barefoot (59.6%, 95% CI: 57.8–61.5), drinking contaminated water (52.9%, 95% CI: 51.0–54.8), playing in dirty places (21.8%, 95% CI: 20.2–23.3) and dirty hands (2.3%, 95% CI: 1.7–2.9). Conclusion Semi-annual deworming campaigns have proved effective in significantly reducing helminthic infections in most of the districts in Uganda. Regular evaluations are vital to assess impact of the interventions and guide programme implementation. Our data shows that the prevalence of infection has been reduced to a level where STH morbidity is no longer of public health importance in most districts surveyed.

INTRODUCTION Lango region is the only known endemic region for urinary and intestinal schistosomiasis in Uganda. Although there has been no significant improvement in sanitation and safe water supply in the region over years, the endemicity and prevalence of Schistosoma haematobium, in particular, have declined, perhaps due to yearly mass treatment campaigns implemented since 2003. METHODS We report the epidemiology of Urinary and Intestinal schistosomiasis in Lango since 1951-2011 determined through Microscopic examinations for S.mansoni and S.haematobium respectively. A retrospective data review from 195-2011 was done to establish the prevalence over the years in the region. We performed Poisson regression analysis to observe trends in epidemiology before and after control was initiated in 2002. In addition, malacological surveys were undertaken in 2007 to assess local transmission potential. FINDINGS Contrary to earlier records, S. haematobium was low and confined to a few putative foci, with declined in infections from 28.2% in 1951 to 2.48% by 2011. Although this decline can be attributed to control, this was already much lower in 1967 than 1951, long before control interventions began suggesting that environmental changes may have made the habitat less suitable for the transmission of S.haematobium. Compared to the historical records S.mansoni prevalence first increased up immediately before control interventions in 2003, significantly declined (p=

Schistosomiasis, one of the 17 neglected tropical diseases listed by the World Health Organization, presents a substantial public health and economic burden. Of the 261 million people requiring preventive chemotherapy for schistosomiasis in 2013, 92% of them lived in sub-Saharan Africa and only 12.7% received preventive chemotherapy. Moreover, in 2010, the WHO reported that schistosomiasis mortality could be as high as 280 000 per year in Africa alone. In May 2012 delegates to the sixty-fifth World Health Assembly adopted resolution WHA65.21 that called for the elimination of schistosomiasis, and foresees the regular treatment of at least 75% of school age children in at-risk areas. The resolution urged member states to intensify schistosomiasis control programmes and to initiate elimination campaigns where possible. Despite this, in June 2015, schistosomiasis was indicated to have the lowest level of preventive chemotherapy implementation in the spectrum of neglected tropical diseases. It was also highlighted as the disease most lacking in progress. This is perhaps unsurprising, given that it was also the only NTD with access to drug donations but without a coalition of stakeholders that collaborates to boost commitment and implementation. As a consequence, and to ensure that the WHO NTDs Roadmap Targets of 2012 and World Health Assembly Resolution WHA65.21 are met, the Global Schistosomiasis Alliance (GSA) has been set up. Diverse and representative, the GSA aims to be a partnership of endemic countries, academic and research institutions, international development agencies and foundations, international organizations, non-governmental development organizations, private sector companies and advocacy and resource mobilisation partners. Ultimately, the GSA calls for a partnership to work for the benefit of endemic countries by addressing health inequity and rural poverty. Electronic supplementary material The online version of this article (doi:10.1186/s40249-017-0280-8) contains supplementary material, which is available to authorized users.

SUMMARYEarly in the history of schistosomiasis research, children under 5 years of age were known to be infected. Although this problem was recognized over 100 years ago, insufficient action has been taken to address this issue. Under current policy, such infected children only receive their first antiparasitic treatment (praziquantel – PZQ) upon entry into primary school as current mass drug administration programmes typically target school-aged children. For many infected children, they will wait up to 6 years before receiving their first medication and significant schistosomiasis-related morbidity may have already established. This inequity would not be accepted for other diseases. To unveil some of the reasons behind this neglect, it is paramount to understand the intricate historical relationship between schistosomiasis and British Imperial medicine, to underline its lasting influence on today's public health priorities. This review presents a perspective on the historical neglect of paediatric schistosomiasis, focusing on important gaps that persist from the early days after discovery of this parasite. Looking to end this inequity, we address several issues that need to be overcome to move forward towards the lasting success of schistosomiasis control and elimination efforts.

Background Intestinal schistosomiasis is of public health importance in Uganda but communities living above 1400 m are not targeted for control as natural transmission is thought unlikely. To assess altitudinal boundaries and at-risk populations, conjoint malacological and epidemiological surveys were undertaken on Mount Elgon (1139 m–3937 m), in Fort Portal crater lakes and in the Rwenzori Mountains (1123 m–4050 m). Methods Seventy freshwater habitats [Mount Elgon (37), Fort Portal crater lakes (23), Rwenzori Mountains (8) and Lake Albert (2)] were inspected for Biomphalaria species. Water temperature, pH and conductivity were recorded. A parasitological examination of 756 schoolchildren [Mount Elgon (300), Fort Portal crater lakes (456)] by faecal microscopy of duplicate Kato-Katz smears from two consecutive stool samples was bolstered by antigen (urine-CCA dipstick) and antibody (SEA-ELISA) diagnostic assays. Results Biomphalaria spp. was found up to 1951 m on Mount Elgon and 1567 m in the Fort Portal crater lakes. Although no snail from Mount Elgon shed cercariae, molecular analysis judged 7.1% of snails sampled at altitudes above 1400 m as having DNA of Schistosoma mansoni; in Fort Portal crater lakes three snails shed schistosome cercariae. Prevalence of intestinal schistosomiasis as measured in schoolchildren by Kato-Katz (Mount Elgon = 5.3% v. Fort Portal crater lakes = 10.7%), CCA urine-dipsticks (18.3% v. 34.4%) and SEA-ELISA (42.3% v. 63.7%) showed negative associations with increasing altitude with some evidence of infection up to 2000 m. Conclusions Contrary to expectations, these surveys clearly show that natural transmission of intestinal schistosomiasis occurs above 1400 m, possibly extending up to 2000 m. Using spatial epidemiological predictions, this now places some extra six million people at-risk, denoting an expansion of preventive chemotherapy needs in Uganda. Electronic supplementary material The online version of this article (doi:10.1186/s40249-017-0248-8) contains supplementary material, which is available to authorized users.

In wastewater systems in Kampala, Uganda, microbial contamination has increased over the past two decades. Those people who live or work along the Nakivubo channel and wetland and those who use the recreational areas along the shores of Lake Victoria are at an elevated risk of gastrointestinal infections. A quantitative microbial risk assessment (QMRA) was applied for five population groups, characterised by different levels of exposure to wastewater in the Nakivubo area, namely: (i) slum dwellers at risk of flooding; (ii) children living in these slum settlements; (iii) workers maintaining the drainage system or managing faecal sludge (sanitation workers); (iv) urban farmers; and (v) swimmers in Lake Victoria. The QMRA was based on measured concentrations of Escherichia coli, Salmonella spp. and Ascaris spp. eggs in wastewater samples. Published ratios between measured organism and pathogenic strains of norovirus, rotavirus, Campylobacter spp., pathogenic E. coli, pathogenic Salmonella spp., Cryptosporidium spp. and Ascaris lumbricoides were used to estimate annual incidence of gastrointestinal illness and the resulting disease burden. The QMRA estimated a total of 59,493 disease episodes per year across all 18,204 exposed people and an annual disease burden of 304.3 disability-adjusted life years (DALYs). Incidence estimates of gastrointestinal disease episodes per year were highest for urban farmers (10.9) and children living in slum communities (8.3), whilst other exposed groups showed lower incidence (, Microbial Risk Analysis, 4, ISSN:2352-3522

As part of an epidemiological survey for gastrointestinal parasites in school children across five primary schools on the shoreline of Lake Albert, the prevalence of giardiasis was 87.0% (n = 254) as determined by real-time PCR analysis of faecal samples with a genus-specific Giardia 18S rDNA probe. Faecal samples were further characterised with taxon assemblage-specific triose phosphate isomerase (TPI) Taqman® probes and by sequence characterisation of the β-giardin gene. While less sensitive than the 18S rDNA assay, general prevalence by TPI probes was 52.4%, with prevalence by taxon assemblage of 8.3% (assemblage A), 35.8% (assemblage B) and 8.3% co-infection (A & B assemblages). While assemblage B was dominant across the sample, proportions of assemblages A and B, and co-infections thereof, varied by school and by age of child; mixed infections were particularly common at Runga school (OR = 6.9 [95% CI; 2.5, 19.3]) and in children aged 6 and under (OR = 2.7 [95% CI; 1.0, 7.3]). Infection with assemblage B was associated with underweight children (OR = 2.0 [95% CI; 1.0, 3.9]). The presence of each assemblage was also confirmed by sequence analysis of the β-giardin gene finding sub-assemblage AII and further genetic diversity within assemblage B. To better explore the local epidemiology of giardiasis and its impact on child health, additional sampling of school children with assemblage typing would be worthwhile. Keywords: Giardia duodenalis, Real-time PCR, Assemblage B, β-giardin, Wasting

Intestinal schistosomiasis continues to be hyper-endemic in the fishing community of Bugoigo located on the eastern shore of Lake Albert, Uganda. Our study aimed to identify the factors that determine the local distribution and abundance of Biomphalaria, as well as infection(s) with Schistosoma mansoni inclusive of their genetic diversity. In addition, a DNA barcoding approach was taken to genotype schistosome cercariae, exploring the micro-epidemiology of infections. Over a 3-week period in June-July 2010, several hundred Biomphalaria spp. were collected, together with environmental information, from 10 selected sites, representative of both putative wave-exposed (n=5) and wave-sheltered shorelines (n=5). A Mann-Whitney U-test and a generalized linear model were used to assess associations with snail abundance and parasite infections across the shoreline. Levels of local wave action were recorded over the 19-day period using digital accelerometers. The general absence of wave action on the sheltered shoreline likely helped to raise and focalize other environmental parameters, such as water conductivity by lack of mixing, that foster transmission of intestinal schistosomiasis. Over the study period, a total of 10 infected snails were encountered and a selection of schistosome cercariae from each infected snail was harvested for analysis by DNA barcoding. In total, 91 DNA barcodes were generated with 15 unique barcode types identified. Of these, 4 barcodes had been found previously in Lake Albert and (or) Victoria, the remaining 11 were newly encountered here and described. The distribution of DNA barcodes across infected snails and sampled locations revealed a complicated spatial sub-structuring. By shedding new light on the fine-scale patterning of infections, DNA barcoding has revealed a rather heterogeneous landscape of cercariae, likely inclusive of multi-miracidial infections within the snail, which will in turn interplay with human water contact activities to shape the genetic diversity of worm populations within infected people.

Schistosomiasis remains one of the most prevalent parasitic diseases in the tropics and subtropics, but current statistics are outdated due to demographic and ecological transformations and ongoing control efforts. Reliable risk estimates are important to plan and evaluate interventions in a spatially explicit and cost-effective manner. We analysed a large ensemble of georeferenced survey data derived from an open-access neglected tropical diseases database to create smooth empirical prevalence maps for Schistosoma mansoni and Schistosoma haematobium for a total of 13 countries of eastern Africa. Bayesian geostatistical models based on climatic and other environmental data were used to account for potential spatial clustering in spatially structured exposures. Geostatistical variable selection was employed to reduce the set of covariates. Alignment factors were implemented to combine surveys on different age-groups and to acquire separate estimates for individuals aged ≤20 years and entire communities. Prevalence estimates were combined with population statistics to obtain country-specific numbers of Schistosoma infections. We estimate that 122 million individuals in eastern Africa are currently infected with either S. mansoni, or S. haematobium, or both species concurrently. Country-specific population-adjusted prevalence estimates range between 12.9% (Uganda) and 34.5% (Mozambique) for S. mansoni and between 11.9% (Djibouti) and 40.9% (Mozambique) for S. haematobium. Our models revealed that infection risk in Burundi, Eritrea, Ethiopia, Kenya, Rwanda, Somalia and Sudan might be considerably higher than previously reported, while in Mozambique and Tanzania, the risk might be lower than current estimates suggest. Our empirical, large-scale, high-resolution infection risk estimates for S. mansoni and S. haematobium in eastern Africa can guide future control interventions and provide a benchmark for subsequent monitoring and evaluation activities.

In order to investigate the capacity of being intermediate host for Schistosoma mansoni, the Ugandan F1 generation of Biomphalaria snail species that were laboratory-bred from parent populations originally collected from either Lake Victoria or Lake Albert was challenged with sympatric and non-sympatric S. mansoni isolates. After a prepatent period of 20 days, a daily 10-hourly snail shedding for cercariae was done to determine the infection rate, cercarial production per hour and survival period of infected snails. The study suggests that when parasite strains from a different geographical origin is used for infection, survival of infected snails increase, leading to an increased transmission potential. Although earlier literature had indicated that the Lake Victoria Biomphalaria sudanica is refractory to S. mansoni, we showed that all Ugandan Biomphalaria spp., including B. sudanica from all locations, were highly susceptible to the S. mansoni isolates. Thus if B. choanomphala, which is an efficient intermediate host in Lake Victoria, is given an opportunity to occupy Lake Albert, it will most likely be compatible with the Albertine S. mansoni parasites. Equally, if B. stanleyi, currently restricted to Lake Albert invades Lake Victoria, it is likely to act as an efficient intermediate host. Future work should concentrate on intraspecific population-level differences in compatibility.

BACKGROUND A sensitive and reliable rapid diagnostic test (RDT) which should have comparable diagnostic performance against reference host serological methods is urgently needed for use in point-of-care (POC) diagnosis of intestinal schistosomiasis in pre school-aged children. METHODS The diagnostic accuracy of a RDT incorporating Schistosoma mansoni cercarial transformation fluid (SmCTF) for anti-schistosome antibody detection was evaluated with serum samples from a cohort of children from Uganda: 42 children aged under the age of 3 years and 40 children aged between 3 and 5 years. The infection status of these children had been previously determined by inspection of quadruplicate Kato-Katz faecal smears, a single urine circulating cathodic antigen (CCA) dipstick and antibody titres to S. mansoni soluble egg antigen (SmSEA) with a commercially available ELISA. RESULTS Upon comparison with quadruplicate Kato-Katz the sensitivity and specificity of the RDT were 75.7% and 31.1%, respectively. When using the SmSEA-ELISA as an alternate reference test, the RDT achieved 81.3% sensitivity and 61.1% specificity. Sensitivity and specificity compared to the urine-CCA test was 74.5% and 32.3% respectively. Sensitivity differed significantly according to age group. CONCLUSIONS The performance of the RDT within this study appeared favourable when compared with the currently-available SmSEA-ELISA. Looking to the future a serological POC test would be particularly promising for use in disease mapping in younger children especially in guiding administration of praziquantel treatment in selective treatment settings.

BACKGROUND The current recommended control strategy for schistosomiasis is annual treatment using 40 mg/kg of praziquantel. However, praziquantel is only effective on adult worms and giving a second dose may increase its efficacy. We assessed the effect of one versus two doses of praziquantel on cure rate and re-infection with Schistosoma mansoni in a high endemic community along Lake Victoria, Uganda. METHODOLOGY To investigate the effect of the two regimens, 395 infected people were randomised into two groups; one received a single standard dose of praziquantel (Distocide® 600 mg, Shin Poong Pharmaceuticals, Seoul, Republic of Korea), 40mg/kg body weight, while the other group received a second dose 2 weeks later. Cure rate and infection intensity were assessed 9 weeks after the first treatment using standard parasitological procedures. Re-infection levels were monitored 8 and 24 months after treatment. RESULTS Those who received two doses were more likely to be cured (69.7%) compared to those who received a single dose (47.9%) (χ(2) = 18.5, p < 0.001). Geometric mean intensity (GMI) of infection at 9 weeks (eggs per gram of faeces [epg]) was 12.0 epg (CI95: 8.9-16.1) for individuals who received 2 doses and 22.1 epg (CI95: 16.9-28.8) for those in the single dose arm. Eight months after treatment, prevalence of re-infection for individuals in the double dose arm (61.6%, CI95: 50.2-73.1) was not significantly different from that of those in a single dose arm (68.3%, CI95: 59.9-76.8). The difference in GMI of re-infection for individuals in the single dose arm (33.8 epg, CI95: 23.2-49.3) and those in the double dose arm (34.5 epg, CI95: 24.7-48.1) was not significant. Twenty four months after treatment, prevalence of re-infection was not significantly different. The difference in GMI of re-infection for those in the single dose arm (57.5 epg, CI95: 33.9-97.5) and those in the double dose arm (42.2 epg, CI95: 29.9-59.6) was also insignificant. CONCLUSION Our results suggest that a second dose of praziquantel given 2 weeks after the first dose improves cure rate and reduces S. mansoni infection intensity. However, there is no added advantage on reduction of S. mansoni re-infection by administering two doses of praziquantel. CLINICAL TRIALS.GOV IDENTIFIER: NCT00215267.

In the major wastewater systems in Kampala, Uganda, microbial contamination has consistently increased over the past two decades. People living and working along the Nakivubo channel and wetland, o...