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Intestinal schistosomiasis is hyperendemic in many sub-Saharan African countries. In Uganda, it is endemic at both Lake Albert (LA) and Lake Victoria (LV) and caused by S. mansoni that uses Biomphalaria snails as obligatory intermediate snail hosts. To shed light on local patterns of infection, we utilised two PCR-based methods to detect S. mansoni within Biomphalaria spp. as collected at the Ugandan shorelines of Lake Albert and Lake Victoria from 2009-2010. Overall, at our Lake Albert sites, the mean infection prevalence was 12.5% (15 of 120 snails), while at our Lake Victoria sites the prevalence was 5% (3 of 60 snails). At our Lake Albert sites, the highest infection prevalence of 13.3% (8 of 60 snails) was at Walukuba, while at our Lake Victoria sites, the highest infection prevalence of 10% (2 of 20 snails) was at Lwanika. Three species of Biomphalaria, B. pfeifferi, B. stanleyi and B. sudanica, were identified at our Lake Albert collection sites, while only a single species, B. choanomphala, was identified at our Lake Victoria collection sites. Biomphalaria stanleyi (2 of 20 snails; 15%) had the highest infection prevalence, followed by B. sudanica (5 of 60 snails; 13.3%), B. pfeifferi (4 of 40 snails; 10%) and B. choanomphala (3 of 60 snails; 5%). Of the Biomphalaria species identified, B. choanomphala had the highest haplotype (gene) diversity score, followed by B. stanleyi, B. sudanica and B. pfeifferi. Sites with a higher mean prevalence of S. mansoni infection had higher intra-species haplotype diversity scores than sites with a lower mean prevalence. The wet seasons (LA: 13.3%; LV: 8.7%) had a consistently higher mean infection prevalence of S. mansoni than the dry seasons (LA: 9.5%; LV: 5%) for all species and all sites tested at both Lake Albert (n = 480) and Lake Victoria (n = 320), though the difference was not statistically significant., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Andrus et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

School-aged children (SAC) have a considerable burden of intestinal schistosomiasis in Madagascar yet its burden in pre-school aged children (PSAC) is currently overlooked. To assess the at-risk status of PSAC, we undertook a pilot epidemiological survey in June 2019 examining children (n = 89), aged 2-4-years of balanced gender, in six remote villages in Marolambo District, Madagascar. Diagnosis included use of urine-circulating cathodic antigen (CCA) dipsticks and coproscopy of stool with duplicate Kato-Katz (K-K) thick smears. Prevalence of intestinal schistosomiasis by urine-CCA was 67.4% (95% confidence interval [CI]: 56.5-77.2%) and 35.0% (95% CI: 24.7-46.5%) by K-K. The relationship between faecal eggs per gram (epg) and urine-CCA G-scores (G1 to G10) was assessed by linear regression modelling, finding for every increment in G-score, epg increased by 20.4 (6.50-34.4, P = 0.006). Observed proportions of faecal epg intensities were light (78.6%), moderate (17.9%) and heavy (3.6%). Soil-transmitted helminthiasis was noted, prevalence of ascariasis was 18.8% and trichuriasis was 33.8% (hookworm was not reported). Co-infection of intestinal schistosomiasis and soil-transmitted helminthiasis occurred in 36.3% of PSAC. These results provide solid evidence highlighting the overlooked burden of intestinal schistosomiasis in PSAC, and they also offer technical  guidance for better surveillance data for the Madagascan national control programme.

Schistosomiasis is a major public health problem in Madagascar. The WHO recommends preventive chemotherapy by mass drug administration (MDA) with praziquantel as the primary approach to control Schistosoma mansoni-related morbidity in endemic populations, alongside complementary interventions such as health education. The impact of annual MDA and health education programs was assessed in the hard-to-reach Marolambo district of eastern Madagascar, an area endemic for S. mansoni. Repeated cross-sectional studies undertaken 2015-2019 examined between 300 and 381 school-aged children (aged 5-14 years) annually. The prevalence and infection intensity of S. mansoni were assessed by urine-circulating cathodic antigen (CCA) dipsticks and coproscopy using Kato-Katz (KK) methodologies. After four rounds of annual MDA, a reduction in S. mansoni prevalence was seen in CCA (93.9% in year 1-87.7% in year 5; P = 0.007) and KK (73.9% in year 1-59.4% in year 5; P < 0.0001). The prevalence of heavy-intensity infections roughly halved from 23.7% to 10.1% (P < 0.0001), and the mean intensity of infection fell by 55.0% (480.2-216.3 eggs per gram of feces). A malacological survey found Biomphalaria pfeifferi snail intermediate hosts in multiple water contact sites including rice paddies, streams, and Nosivolo River. Despite reductions in infection prevalence and intensity, schistosomiasis still poses a significant public health challenge in Marolambo district. Twice yearly MDA cycles and/or community-wide MDA are suggested to better reduce infections. Expanding health education, improving standards of water, sanitation and hygiene, and attention on snail-related control will also be important, especially in rice paddy irrigated areas.

Background: Intestinal schistosomiasis was not considered endemic in Lake Malawi until November 2017 when populations of Biomphalaria pfeifferi were first reported; in May 2018, emergence of intestinal schistosomiasis was confirmed. This emergence was in spite of ongoing control of urogenital schistosomiasis by preventive chemotherapy. Our current study sought to ascertain whether intestinal schistosomiasis is transitioning from emergence to outbreak, to judge if stepped-up control interventions are needed., Methods: During late-May 2019, three cross-sectional surveys of primary school children for schistosomiasis were conducted using a combination of rapid diagnostic tests, parasitological examinations and applied morbidity-markers; 1) schistosomiasis dynamics were assessed at Samama (n = 80) and Mchoka (n = 80) schools, where Schistosoma mansoni was first reported, 2) occurrence of S. mansoni was investigated at two non-sampled schools, Mangochi Orphan Education and Training (MOET) (n = 60) and Koche (n = 60) schools, where B. pfeifferi was nearby, and 3) rapid mapping of schistosomiasis, and B. pfeifferi, conducted across a further 8 shoreline schools (n = 240). After data collection, univariate analyses and Chi-square testing were performed, followed by binary logistic regression using generalized linear models, to investigate epidemiological associations., Results: In total, 520 children from 12 lakeshore primary schools were examined, mean prevalence of S. mansoni by 'positive' urine circulating cathodic antigen (CCA)-dipsticks was 31.5% (95% confidence interval [CI]: 27.5-35.5). Upon comparisons of infection prevalence in May 2018, significant increases at Samama (relative risk [RR] = 1.7, 95% CI: 1.4-2.2) and Mchoka (RR = 2.7, 95% CI: 1.7-4.3) schools were observed. Intestinal schistosomiasis was confirmed at MOET (18.3%) and Koche (35.0%) schools, and in all rapid mapping schools, ranging from 10.0 to 56.7%. Several populations of B. pfeifferi were confirmed, with two new eastern shoreline locations noted. Mean prevalence of urogenital schistosomiasis was 24.0% (95% CI: 20.3-27.7)., Conclusions: We notify that intestinal schistosomiasis, once considered non-endemic in Lake Malawi, is now transitioning from emergence to outbreak. Once control interventions can resume after coronavirus disease 2019 (COVID-19) suspensions, we recommend stepped-up preventive chemotherapy, with increased community-access to treatments, alongside renewed efforts in appropriate environmental control.

Background: In Ghana, pre-school-aged children (PSAC) are at risk of intestinal schistosomiasis and are living in need of praziquantel treatment. To better assess the infection burden within this vulnerable demographic group, we have provided a comparative assessment of the prevalence of Schistosoma mansoni in pre-school-aged children by urine circulating cathodic antigen (CCA) dipsticks, real-time PCR Taqman® faecal assays and Kato-Katz coproscopy., Methods: In all, 190 pre-school-aged children were sampled from three endemic communities (viz. Tomefa, Torgahkope/Adakope, and Manheam) around Weija dam, Southern Ghana. Fresh stool and urine samples were collected from all participants for diagnosis., Results: Among all the three communities, the urine-CCA assay recorded the highest prevalence values of 90.5% (95% CI 80.4-96.4), 87.9% (95% CI 76.7-95), and 81.2% (95% CI 69.9-89.6) in Tomefa, Torgahkope/Adakope, and Manheam respectively. Prevalence by real-time PCR was 50% (95% CI 35.5-64.5), 8% (95% CI 2.2-19.2) and 16.7% (95% CI 8.3-28.5), while by Kato-Katz was 55.6% (95% CI 42.5-68.1), 8.6% (95% CI 2.9-19) and 11.6% (95% CI 5.1-21.6) respectively. Children aged 1 year and over were found to be positive with the urine-CCA assay; by the ages of 3-4, over 50% were urine-CCA patent. The sensitivity and specificity of the POC-CCA dipsticks, when compared against the combined results of Kato-Katz/TaqMan results was found to be 84.1% (95% CI = 72.7-92.1) and 12.9% (95% CI = 6.6-22) respectively., Conclusions: We propose that the urine-CCA dipstick may be a useful rapid diagnostic tool to estimate the prevalence of intestinal schistosomiasis in PSAC, particularly in rapid identification of at-risk areas. However, our assessment has shown that it possible to record false positives when compared to combined Kato-Katz and qPCR results. To guide PSAC praziquantel treatment needs, we propose the urine CCA assay should be included in routine surveillance of intestinal schistosomiasis alongside other diagnostics such as Kato-Katz and urine filtration.

Background: A cross-sectional survey was performed to estimate the prevalence of periportal fibrosis in children based on ultrasound examination in the Marolambo district of the Atsinanana region of Madagascar. This is a remote area known to have a high prevalence of intestinal schistosomiasis., Methods: School-aged children (5-14 y) were selected from six villages for parasitological and sonographic examination. Circulating cathodic antigen (CCA) tests and Kato Katz (KK) stool microscopy were performed. Video-clips of liver views were recorded with a SonoSite iViz and interpreted in the UK by comparison with standardised images (WHO protocol)., Results: The prevalence of schistosomiasis according to CCA testing was 97.8% (269/275) and 73.8% (203/275) by KK. Sonographic evidence of periportal fibrosis was observed in 11.3% (31/275). The youngest children with fibrosis were aged 6 y. Fibrosis was more common in older children (p=0.03) but was not associated with either infection intensity category (p=0.07) or gender (p=0.67)., Conclusions: Findings of periportal fibrosis among children in these hard-to-reach villages suggests chronic Schistosoma mansoni infection from a very young age. This may reflect other similarly remote schistosomiasis-endemic areas and reinforces the need to investigate morbidity in neglected communities to understand the true extent of disease burden in endemic countries., (© The Author(s) 2020. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Using the 20-meter shuttle run test (20mSRT) as a morbidity metric, we assessed whether Schistosoma mansoni infection was associated with decreased aerobic capacity in Ugandan children across a range of altitudes, either at low (∼600 m) or high (∼1,000 m) altitudes. A total of 305 children were recruited from six schools within the Buliisa District, Lake Albert, Uganda. A subset ( n = 96) of these had been previously assessed and treated for schistosomiasis ± malaria 2 weeks prior. Fitness scores on the 20mSRT were translated into VO2max using a standardized equation. Unadjusted and multivariable-adjusted analyses were performed using VO2max as the primary outcome. Analysis of fitness scores from 304 children, inclusive of the subset follow-up cohort, revealed a median VO2max of 45.4 mL kg -1 min -1 (interquartile range: 42.9-48.0 mL kg -1 min -1 ). Children residing at high altitudes demonstrated increased aerobic capacities (46.3 versus 44.8 mL kg -1 min -1 , P = 0.031). The prevalence of stunting, wasting, S. mansoni egg patent infection, malaria, giardiasis, anemia, and fecal occult blood were 36.7%, 16.1%, 44.3%, 65.2%, 21.4%, 50.6%, and 41.2%, respectively. Median VO2max was elevated in those previously treated, compared with those newly recruited (46.3 versus 44 mL kg -1 min -1 , P < 0.001). Multivariable-adjusted analysis revealed a strong negative association between S. mansoni egg patent infection and VO2max at low altitude (beta coefficient: -3.96, 95% CI: -6.56 to -137, P = 0.004). This is the first study to document a negative association between S. mansoni infection and aerobic capacity at low altitudes using the 20mSRT.

Programmatic surveillance of intestinal schistosomiasis during control can typically use four diagnostic tests, either singularly or in combination, but these have yet to be cross-compared directly. Our study assembled a complete diagnostic dataset, inclusive of infection intensities, from 258 children from five Ugandan primary schools. The schools were purposely selected as typical of the endemic landscape near Lake Albert and reflective of high- and low-transmission settings. Overall prevalence was: 44.1% (95% CI 38.0-50.2) by microscopy of duplicate Kato-Katz smears from two consecutive stools, 56.9% (95% CI 50.8-63.0) by urine-circulating cathodic antigen (CCA) dipstick, 67.4% (95% CI 61.6-73.1) by DNA-TaqMan® and 75.1% (95% CI 69.8-80.4) by soluble egg antigen enzyme-linked immunosorbent assay (SEA-ELISA). A cross-comparison of diagnostic sensitivities, specificities, positive and negative predictive values was undertaken, inclusive of a latent class analysis (LCA) with a LCA-model estimate of prevalence by each school. The latter ranged from 9.6% to 100.0%, and prevalence by school for each diagnostic test followed a static ascending order or monotonic series of Kato-Katz, urine-CCA dipstick, DNA-TaqMan® and SEA-ELISA. We confirm that Kato-Katz remains a satisfactory diagnostic standalone in high-transmission settings but in low-transmission settings should be augmented or replaced by urine-CCA dipsticks. DNA-TaqMan® appears suitable in both endemic settings though is only implementable if resources permit. In low-transmission settings, SEA-ELISA remains the method of choice to evidence an absence infection. We discuss the pros and cons of each method concluding that future surveillance of intestinal schistosomiasis would benefit from a flexible, context-specific approach both in choice and application of each diagnostic method, rather than a single one-size fits all approach.

Background: A school-based survey was undertaken to assess prevalence and infection intensity of schistosomiasis in school-aged children in the Marolambo District of Madagascar., Methods: School-aged children from six purposively selected schools were tested for Schistosoma haematobium by urine filtration and Schistosoma mansoni using circulating cathodic antigen (CCA) and Kato-Katz stool analysis. The investigators did not address soil-transmitted helminths (STH) in this study., Results: Of 399 school-aged children screened, 93.7% were infected with S. mansoni based on CCA analysis. Kato-Katz analysis of stool revealed S. mansoni infection in 73.6% (215/ 292). Heavy infections (> 400 eggs per gram) were common (32.1%; 69/ 215), with a mean of 482 eggs per gram of stool. Moderate infection intensities were detected in 31.2% (67/ 215) and light infection intensities in 36.7% (79/ 215) of infected participants. No infection with S. haematobium was detected by urine filtration., Conclusions: Intestinal schistosomiasis appears a considerable public health issue in this remote area of Madagascar where there is a pressing need for mass drug administration.

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.

Background: Water-borne parasitic diseases associated with poverty still blight the lives of African school children. In Uganda, intestinal schistosomiasis is still common along the shoreline of Lake Albert, despite ongoing control, and co-infection with giardiasis and malaria is poorly described. To shed light on putative interactions between diseases, a prospective cross-sectional parasitological survey was undertaken in five primary schools., Methods: Stool samples from 254 school children, aged 5-10 years, were examined by microscopy and rapid diagnostic tests (RDTs), with additional real-time PCR assays for detection of Giardia DNA. A finger-prick blood sample was also taken from each child and tested for malaria, and haemoblobin levels measured. Assocations between diseases and anaemia were assessed., Results: Intestinal schistosomiasis (46.5%), giardiasis (41.6%) and malaria (56.2%) were common, and a quarter of children were anaemic (<115 g/L). Up to 87.0% of children were excreting Giardia DNA and the prevalence of heavy infection by real-time PCR (Ct≤19) was 19.5%, being positively associated with light, moderate and heavy egg-patent schistosomiasis, as well as with anaemia., Conclusions: In this setting, an extensive burden of giardiasis was revealed with heavy intensity infections associated with egg-patent intestinal schistosomiasis and anaemia. To improve child health, greater attention on giardiasis is needed along with exploring joined-up actions across diseases that promote better water hygiene and sanitation measures., (© The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Unlabelled: Each year, millions of African children receive praziquantel (PZQ) by mass drug administration (MDA) to treat schistosomiasis at a standard single dose of 40 mg/kg of body weight, a direct extrapolation from studies of adults. A higher dose of 60 mg/kg is also acceptable for refractory cases. We conducted the first PZQ pharmacokinetic (PK) and pharmacodynamic (PD) study in young children comparing dosing. Sixty Ugandan children aged 3 to 8 years old with egg patent Schistosoma mansoni received PZQ at either 40 mg/kg or 60 mg/kg. PK parameters of PZQ racemate and enantiomers (R and S) were quantified. PD outcomes were assessed by standard fecal egg counts and novel schistosome-specific serum (circulating anodic antigen [CAA]) and urine (circulating cathodic antigen [CCA]) antigen assays. Population PK and PD analyses were performed to estimate drug exposure in individual children, and the relationship between drug exposure and parasitological cure was estimated using logistic regression. Monte Carlo simulations were performed to identify better, future dosing regimens. There was marked PK variability between children, but the area under the concentration-time curve (AUC) of PZQ was strongly predictive of the parasitological cure rate (CR). Although no child achieved antigenic cure, which is suggestive of an important residual adult worm burden, higher AUC was associated with greater CAA antigenic decline at 24 days. To optimize the performance of PZQ, analysis of our simulations suggest that higher doses (>60 mg/kg) are needed, particularly in smaller children., Importance: Schistosomiasis is a neglected tropical disease, typically associated with chronic morbidity, and its control is a global health priority. Praziquantel (PZQ) is the only available antiparasitic drug and is often given out, as a single oral dose (40 mg/kg), to school-aged children by mass drug administration (MDA) schemes operating within preventive chemotherapy campaigns as endorsed by the World Health Organization (WHO). This current strategy has several limitations. (i) It excludes preschool children who can be patently infected. (ii) It delivers PZQ at a dose directly extrapolated from adult pharmacological studies. To address these problems, we conducted the first pharmacokinetic and pharmacodynamic study of young children within an area of Uganda where Schistosoma mansoni is hyperendemic. Our results demonstrate that a higher dose (>60 mg/kg) is required, especially in smaller children, and draw attention to the need for further optimization of PZQ treatment based on schistosome antigenic assays, which are more sensitive to pharmacodynamic markers., (Copyright © 2016 Bustinduy et al.)

This study documented the population dynamics of Biomphalaria and 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. Retained Biomphalaria were subsequently monitored in laboratory aquaria for shedding trematode cercariae, which were classified as either human infective (Schistosoma mansoni) or nonhuman infective. The population dynamics of Biomphalaria differed 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 the Biomphalaria collected in Lake Albert (N = 6,183), 8.9% were infected with digenetic trematodes of which 15.8% were shedding S. mansoni cercariae and 84.2% with nonhuman infective cercariae. In Lake Victoria, 2.1% of collected Biomphalaria (N = 13,172) were infected with digenetic trematodes with 13.9% shedding S. mansoni cercariae, 85.7% shedding nonhuman infective cercariae, and 0.4% of infected snails shedding both types of cercariae. Upon morphological identification, species of Biomphalaria infected included B. sudanica, B. pfeifferi, and B. stanleyi in Lake Albert and B. sudanica, B. pfeifferi, and B. choanomphala in Lake Victoria. The study found the physicochemical factors that influenced Biomphalaria population and infections. The number and extent of snails shedding S. mansoni cercariae 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.

An association between late-stage hepatosplenic schistosomiasis and endomyocardial fibrosis (EMF) has been suggested but not proven. We present the case of a 12-year-old Ugandan boy with striking comorbidities, including advanced periportal fibrosis caused by Schistosoma mansoni infection and right ventricular EMF, and discuss the possible correlation between both diseases., (© The American Society of Tropical Medicine and Hygiene.)

Significant numbers of pre-school children are infected with Schistosoma mansoni in sub-Saharan Africa and are likely to play a role in parasite transmission. However, they are currently excluded from control programmes. Molecular phylogenetic studies have provided insights into the evolutionary origins and transmission dynamics of S. mansoni, but there has been no research into schistosome molecular epidemiology in pre-school children. Here, we investigated the genetic diversity and population structure of S. mansoni in pre-school children and mothers living in lakeshore communities in Uganda and monitored for changes over time after praziquantel treatment. Parasites were sampled from children (<6 years) and mothers enrolled in the longitudinal Schistosomiasis Mothers and Infants Study at baseline and at 6-, 12- and 18-month follow-up surveys. 1347 parasites from 35 mothers and 45 children were genotyped by direct sequencing of the cytochrome c oxidase (cox1) gene. The cox1 region was highly diverse with over 230 unique sequences identified. Parasite populations were genetically differentiated between lakes and non-synonymous mutations were more diverse at Lake Victoria than Lake Albert. Surprisingly, parasite populations sampled from children showed a similar genetic diversity to those sampled from mothers, pointing towards a non-linear relationship between duration of exposure and accumulation of parasite diversity. The genetic diversity six months after praziquantel treatment was similar to pre-treatment diversity. Our results confirm the substantial genetic diversity of S. mansoni in East Africa and provide significant insights into transmission dynamics within young children and mothers, important information for schistosomiasis control programmes.

Background: Calprotectin is a calcium-binding cytoplasmic protein found in neutrophils and increasingly used as a marker of bowel inflammation. Fecal occult blood (FOB) is also a dependable indicator of bowel morbidity. The objective of our study was to determine the applicability of these tests as surrogate markers of Schistosoma mansoni intestinal morbidity before and after treatment with praziquantel (PZQ)., Methods: 216 children (ages 3-9 years old) from Buliisa District in Lake Albert, Uganda were examined and treated with PZQ at baseline in October 2012 with 211 of them re-examined 24 days later for S. mansoni and other soil transmitted helminths (STH). POC calprotectin and FOB assays were performed at both time points on a subset of children. Associations between the test results and infection were analysed by logistic regression., Results: Fecal calprotectin concentrations of 150-300 µg/g were associated with S. mansoni egg patent infection both at baseline and follow up (OR: 12.5 P = 0.05; OR: 6.8 P = 0.02). FOB had a very strong association with baseline anemia (OR: 9.2 P = 0.03) and medium and high egg intensity schistosomiasis at follow up (OR: 6.6 P = 0.03; OR: 51.3 P = 0.003). Both tests were strongly associated with heavy intensity S. mansoni infections. There was a significant decrease in FOB and calprotectin test positivity after PZQ treatment in those children who had egg patent schistosomiasis at baseline., Conclusions: Both FOB and calprotectin rapid assays were found to correlate positively and strongly with egg patent S. mansoni infection with a positive ameloriation response after PZQ treatment indicative of short term reversion of morbidity. Both tests were appropriate for use in the field with excellent operational performance and reliability. Due to its lower-cost which makes its scale-up of use affordable, FOB could be immediately adopted as a monitoring tool for PC campaigns for efficacy evaluation before and after treatment.

We conducted the first meta-analysis of ten Schistosoma haematobium (one published and nine unpublished) and eight Schistosoma mansoni (two published and six unpublished) microsatellite datasets collected from individual schistosome-infected school-children across six sub-Saharan Africa countries. High levels of genetic diversity were documented in both S. haematobium and S. mansoni. In S. haematobium populations, allelic richness did not differ significantly between the ten schools, despite widely varying prevalences and intensities of infection, but higher levels of heterozygote deficiency were seen in East than in West Africa. In contrast, S. mansoni populations were more diverse in East than West African schools, but heterozygosity levels did not vary significantly with geography. Genetic structure in both S. haematobium and S. mansoni populations was documented, at both a regional and continental scale. Such structuring might be expected to slow the spread to new areas of anti-schistosomal drug resistance should it develop. There was, however, limited evidence of genetic structure at the individual host level, which might be predicted to promote the development or establishment of drug resistance, particularly if it were a recessive trait. Our results are discussed in terms of their potential implications for the epidemiology and evolution of schistosomes as well as their subsequent control across sub-Saharan Africa., (Copyright © 2012 Elsevier B.V. All rights reserved.)

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., (Copyright © 2012 Elsevier B.V. All rights reserved.)

A study to investigate the effect of environmental predictors on abundance of Biomphalaria, the intermediate host snails of Schistosoma mansoni, was carried out on two small islands in Lake Victoria, Uganda. Malacological surveys were performed at 40 shoreline sites on Kimi and Ngamba islands documenting occurrence of Biomphalaria; other environmental and limnological conditions were also recorded, including gastropod community diversity. Snails were examined for shedding of schistosomes and emerging cercariae were DNA 'barcoded'. For population genetics analysis of Biomphalaria, snails from four populations from each island were also sequenced. Aquatic phosphate concentrations were higher on Kimi island, confirming greater anthropogenic influence, although, snail species diversity and community assemblages were not significantly different between islands. Bayesian geostatistical models were fitted to assess the effect of environmental factors on Biomphalaria abundance and snails' risk of shedding schistosome or non-schistosome cercariae. No factors were found to be significant in the spatial model. The local population genetics of S. mansoni and Biomphalaria on each island followed similar patterns as that seen in previous studies on a lake-wide basis. These findings suggest that smaller scale studies may prove useful as proxies for regional level investigations, with reduced logistical and resource output required. However, further research should also include surveys of terminal host parasite burden, as these will affect even micro-scale dynamics of parasite-intermediate host interactions, as well as be important from a public health perspective in their own right., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Following major water development schemes in the 1980s, schistosomiasis has become a serious parasitic disease of children living in the Senegal River Basin. Both urogenital (Schistosoma haematobium) and intestinal (Schistosoma mansoni) schistosomiasis can be highly prevalent in school-aged children, with many individuals infected with both parasites. In order to investigate the transmission and re-infection dynamics of both parasite species, single and mixed infection foci at three villages (Nder and Temeye; S. mansoni and S. haematobium foci and Guia; S. haematobium focus) were studied. In each focus infected children were identified and selected for a 12-month study involving two treatments with praziquantel (40mg/kg) three weeks apart at the beginning of the study and again 6 months into the study. Urine and stool samples were examined for schistosome eggs before and at 6 weeks and 6 months after chemotherapy. Prevalence and intensity of infection were recorded for each child at each time point. Before treatment, in all three villages, the prevalence and intensity of infection was extremely high for both S. mansoni (79-100%) and S. haematobium (81-97%). With the first round of chemotherapy sufficient cure rates (CRs) of both species were achieved in all villages (38-96%) with high egg reduction rates (ERRs) (97-99%). The data show that high and rapid re-infection rates occur, especially for S. mansoni, within a six-month period following treatment. Re-infection must be highly linked to ecological and seasonal factors. The persistence of S. mansoni in Nder could raise concern as levels of infection intensity remain high (geometric mean intensity at baseline 653epg changed to 705epg at 12 months) after four rounds of chemotherapy. This phenomenon could be explained by extremely rapid re-infection dynamics or a sub-optimal efficacy of praziquantel against S. mansoni in this village. High intensities in mixed infections may influence disease epidemiology and control warranting further studies. The disease situation in the SRB must be monitored closely and new treatment regimes should be designed and implemented to control schistosomiasis in the school-age population., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The regular administration of the anthelminthic drug praziquantel (PZQ) to school-aged children (and other high-risk groups) is the cornerstone of schistosomiasis control. Whilst the performance of PZQ against single schistosome species infections is well-known, performance against mixed species infections is less so, as are patterns of re-infection following treatment. To address this, a study using a double treatment with PZQ, administered at 40 mg/kg spaced by 3 weeks, took place in two mixed intestinal-urogenital schistosomiasis foci in northern Cameroon (Bessoum and Ouro-Doukoudje) and in one single intestinal schistosomiasis infection focus (Makenene). A total of just under 1000 children were examined and the Schistosoma-infected children were re-examined at several parasitological follow-ups over a 1-year period posttreatment. Overall cure rates against Schistosoma spp. in the three settings were good, 83.3% (95% confidence interval (CI)=77.9-87.7%) in Bessoum, 89.0% (95% CI=79.1-94.6%) in Ouro Doukoudje, and 95.3% (95% CI=89.5-98.0%) in Makenene. Interestingly, no case of mixed schistosome infection was found after treatment. Cure rates for S. mansoni varied from 99.5% to 100%, while that for S. haematobium were considerably lower, varying from 82.7% to 88.0%. Across transmission settings, patterns of re-infection for each schistosome species were different such that generalizations across foci were difficult. For example, at the 6-month follow-up, re-infection rates were higher for S. haematobium than for S. mansoni with re-infection rates for S. haematobium varying from 9.5% to 66.7%, while for S. mansoni, lower rates were observed, ranging between nil and 24.5%. At the 12-month follow-up, re-infection rates varied from 9.1% to 66.7% for S. haematobium and from nil to 27.6% for S. mansoni. Alongside these parasitological studies, concurrent malacological surveys took place to monitor the presence of intermediate host snails of schistosomiasis. In the two northern settings, three species of Bulinus (intermediate host snail of S. haematobium) were collected; i.e. Bulinus truncatus, B. globosus and B. senegalensis, however, Biomphalaria pfeifferi (intermediate host snail of S. mansoni) was much rarer despite repeated and intensive searching and was suggestive of limited local transmission potential of S. mansoni during this time. While this study highlights that performance of PZQ was satisfactory in this region, with somewhat greater impact upon intestinal than urogenital schistosomiasis, the dynamics of local transmission are shown, however, to be complex., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Schistosoma mansoni is a widespread human helminth and causes intestinal schistosomiasis in 54 countries, mainly across Africa but also in Madagascar, the Arabian Peninsula and the neotropics. The geographical range of this parasite relies on the distribution of certain species of freshwater pulmonate snails of the genus Biomphalaria. Whilst S. mansoni is known to exhibit high population diversity the true extent of this diversity is still to be fully elucidated as sampling of this taxon progressively accrues. Here a DNA 'barcoding' approach is taken using sequence analysis of a 450bp region within the mitochondrial cox1 gene to assess the genetic diversity within a large number of S. mansoni larval stages collected from their natural human hosts across sub-Saharan Africa. Five hundred and sixty one individual parasite samples were examined from 22 localities and 14 countries. Considerable within-species diversity was found with 120 unique haplotypes splitting geographically into five discrete lineages. The highest diversity was found in East Africa with samples forming three of the five lineages. Less diversity was found in the Far and Central Western regions of Africa with haplotypes from the New World showing a close affinity to the Far Western African S. mansoni populations supporting the hypothesis of a colonisation of South America via the West African slave trade. The data are discussed in relation to parasite diversity and disease epidemiology., (Copyright © 2012 Elsevier B.V. All rights reserved.)

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.

Specific immunoglobulin E (IgE) responses are upregulated during chronic schistosome infection and during allergy. These responses are tightly regulated during schistosomiasis. We have previously shown that IgE regulation depends on the extent and length of exposure to individual parasite allergen-like proteins. Here we compare the development of IgE and immunoglobulin G4 (IgG(4)) responses to the differentially expressed allergen-like proteins SmTAL1 and SmTAL2 among preschool-aged children from 2 villages with different levels of Schistosoma mansoni transmission. We found a lack of SmTAL1 responsiveness among all children, but evidence for IgG(4)-dependent IgE-SmTAL2 desensitization in both villages, occurring earlier among children from the village where the level of transmission was greater. Findings provide insights into the development and regulation of allergic-type immune responses.

Background: The World Health Organization now recommends the provision of praziquantel treatment to preschool-aged children infected with schistosomiasis. For intestinal schistosomiasis the current operational field diagnostic standard is examination of a thick Kato-Katz smear by microscopy prepared from a single stool specimen, and although pragmatic, this methodology has well-known shortcomings. Here, as a potential alternative, the performance of the urine circulating cathodic antigen (CCA) dipstick test was assessed in terms of disease-mapping and point-of-care diagnosis for intestinal schistosomiasis in preschool-aged children. Our manuscript reports on findings at baseline and at the end of a one-year longitudinal treatment study., Methodology/principal Findings: A total of 925 children (mean age 2.8 years) were initially recruited from six lakeshore villages representative of high, moderate and low levels of disease transmission. At baseline, all children were tested for intestinal schistosomiasis by microscopic examination of duplicate Kato-Katz smears prepared from a single stool faecal, by antigen detection with the urine CCA dipstick test and by serology with a commercially available ELISA test (as 'gold-standard') that measures host antibody titres to soluble egg antigens. As a point-of-care diagnosis, the urine CCA dipstick test achieved sensitivity and specificity values ranging from 52.5-63.2% and 57.7-75.6%, respectively, with faecal microscopy achieving very high specificities (>87%) but sensitivities as low as 16.7% in the low transmission setting., Conclusion/significance: The urine CCA test was shown to be more effective than faecal microscopy especially in lower transmission settings. The diagnostic performance of this test was not significantly impacted by treatment history or co-infections with other intestinal helminths.

The establishment of a national control programme (NCP) in Uganda has led to routine treatment of intestinal schistosomiasis with praziquantel in the communities along Lake Albert. However, because regular water contact remains a way of life for these populations, re-infection continues to mitigate the sustainability of the chemotherapy-based programme. A six-month longitudinal study was conducted in one Lake Albert community with the aim of characterizing water contact exposure and infection among mothers and their young preschool-aged children as the latter are not yet formally included within the NCP. At baseline the cohort of 37 mothers, 36 preschool-aged children had infection prevalences of 62% and 67%, respectively, which diminished to 20% and 29%, respectively, at the 6-month post-treatment follow-up. The subjects wore global positioning system (GPS) datalogging devices over a 3-day period shortly after baseline, allowing for the estimation of time spent at the lakeshore as an exposure metric, which was found to be associated with prevalence at follow-up (OR = 2.1, P = 0.01 for both mothers and young children and odds ratio (OR) = 4.4, P = 0.01 for young children alone). A social network of interpersonal interactions was also derived from the GPS data, and the exposures were positively associated both with the number and duration of peer interaction, suggesting the importance of socio-cultural factors associated with water contact behaviour. The findings illustrate reduction in both prevalence and intensity of infection in this community after treatment as well as remarkably high rates of water contact exposure and re-infection, particularly among younger children. We believe that this should now be formally considered within NCP, which may benefit from more in-depth ethnographic exploration of factors related to water contact as this should provide new opportunities for sustaining control.

There is a need for field-applicable markers to assess morbidity associated with intestinal schistosomiasis, especially in the context of preventive chemotherapy in young children. We investigated whether fecal occult blood (FOB) point-of-care tests could be used to assess intestinal pathology over a 12-month period in a cohort of 382 children (< 5 years of age). We found a strong association between egg-patent schistosomiasis and FOB at baseline (odds ratio [OR] = 3.1, P < 0.0001), 6 months (OR = 3.4, P < 0.0001), and 12 months (OR = 3.5, P < 0.0001), despite repeated chemotherapy. There were tendencies for prevalence of FOB to decrease in children who became egg negative and increase in those who became egg positive. Our results demonstrate overt disease in children less than five years of age. We therefore propose that FOB is useful for assessing dynamics of intestinal morbidity in young children at the community level and monitoring changes in morbidity after mass chemotherapy.

Ngamba Island Chimpanzee Sanctuary (NICS) in Lake Victoria, Uganda is currently home to 44 wild-borne, semi-captive chimpanzees. Despite regular veterinary health checks, it only came to light recently that many animals, and sanctuary staff, were naturally infected with Schistosoma mansoni. Indeed, local schistosome transmission appears firmly engrained for intermediate snail hosts can be found along almost the entirety of Ngamba's shoreline. Here, the epidemiology of infection is a dynamic interplay between human and chimpanzee populations, as revealed by genetic analyses of S. mansoni. In this review, our present understanding of this complex and evolving situation is discussed, alongside general disease control activities in Uganda, to highlight future interventions towards stopping schistosome morbidity and transmission within this conservation sanctuary setting., (Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.)

Background: In 2012 the WHO formally recognised that infants and preschool children are at significant risk of schistosomiasis and qualify for treatment with praziquantel (PZQ). Targeted surveys determining both the performance and safety of this drug are now needed in endemic areas. We have formally assessed parasitological cure and putative side-effects in a prospective cohort of Schistosoma mansoni-infected children (aged 5 months-7 years old) in lakeshore settings of Uganda., Methodology/principal Findings: From a total of 369 children found to be egg-patent for intestinal schistosomiasis, 305 were followed-up three to four weeks after PZQ treatment and infection status re-assessed. Separately, a previously tested side-effect questionnaire was employed before and 24 hours after PZQ treatment to assess incidence and amelioration of symptoms in young children and their mothers. While the overall observed parasitological cure was 56.4%, a significant difference was found between a sub-set of children who had a history of multiple PZQ treatments (between one and four in an 18 month period), where cure rate was 41.7%, and those who had never received treatment (cure rate was 77·6%). PZQ proved to be safe, with only mild reported side effects which cleared within a month after treatment. Prevalence of reported symptoms was significantly lower in children than in mothers, and fewer side-effects were reported upon subsequent rounds of PZQ treatment., Conclusion/significance: Our findings show that PZQ treatment of young children resulted in satisfactory cure rates, and marked reduction in egg-output, with only mild and transient reported side-effects. However, the cure rate is clearly lower in younger children and those with history of previous treatment. Cure rate, but not egg reduction rate, was also lower in children with heavier pre-intervention infection intensity. With chemotherapy now recommended as a long-term strategy for disease control in young children, research into optimising the periodicity of targeted treatment strategies is now crucial.

Background: The Kato-Katz is the most common diagnostic method for Schistosoma mansoni infection. However, the day-to-day variability in host egg-excretion and its low detection sensitivity are major limits for its use in low transmission zones and after widespread chemotherapy. We evaluated the accuracy of circulating cathodic antigen (CCA) urine-assay as a diagnostic tool of S. mansoni. In comparison, a low sensitive CCA test (CCA-L) was assessed., Methodology: THE STUDY WAS CONDUCTED IN THREE SETTINGS: two foci with single S. mansoni infections (settings A and B), and one mixed S. mansoni - S. haematobium focus (setting C). Stool and urine samples were collected from school-children on three consecutive days. Triplicate Kato-Katz readings were performed per stool sample. Each urine sample was tested with one CCA and only the first urine sample was subjected to CCA-L. Urine samples were also examined for S. haematobium eggs using the filtration method and for microhaematuria using urine reagent strips. Overall, 625 children provided three stool and three urine samples., Principal Findings: Considering nine Kato-Katz thick smears as 'reference' diagnostic test, the prevalence of S. mansoni was 36.2%, 71.8% and 64.0% in settings A, B and C, respectively. The prevalence of S. haematobium in setting C was 12.0%. The sensitivities of single Kato-Katz, CCA and CCA-L from the first stool or urine samples were 58%, 82% and 46% in setting A, 56.8%, 82.4% and 68.8% in setting B, and 49.0%, 87.7% and 55.5% in setting C. The respective specificities were 100%, 64.7% and 100%; 100%, 62.3% and 91.3%; and 100%, 42.5% and 92.0%. Mixed infection with S. haematobium did not influence the CCA test results for S. mansoni diagnosis., Conclusions/significance: Urine CCA revealed higher sensitivity than CCA-L and triplicate Kato-Katz, and produced similar prevalence as nine Kato-Katz. It seems an attractive method for S. mansoni diagnosis.

Where very young children come into contact with water containing schistosome cercariae, infections occur and schistosomiasis can be found. In high transmission environments, where mothers daily bathe their children with environmentally drawn water, many infants and preschool-aged children have schistosomiasis. This 'new' burden, inclusive of co-infections with Schistosoma haematobium and Schistosoma mansoni, is being formally explored as infected children are not presently targeted to receive praziquantel (PZQ) within current preventive chemotherapy campaigns. Thus an important PZQ treatment gap exists whereby infected children might wait up to 4-5 years before receiving first treatment in school. International treatment guidelines, set within national treatment platforms, are presently being modified to provide earlier access to medication(s). Although detailed pharmacokinetic studies are needed, to facilitate pragmatic dosing in the field, an extended 'dose pole' has been devised and epidemiological monitoring has shown that administration of PZQ (40 mg/kg), in either crushed tablet or liquid suspension, is both safe and effective in this younger age-class; drug efficacy, however, against S. mansoni appears to diminish after repeated rounds of treatment. Thus use of PZQ should be combined with appropriate health education/water hygiene improvements for both child and mother to bring forth a more enduring solution.

Anaemia is a severe public health issue among African preschool-aged children, yet little effective progress has been made towards its amelioration, in part due to difficulties in unravelling its complex, multifactorial aetiology. To determine the current anaemia situation and assess the relative contribution of malaria, intestinal schistosomiasis and infection with soil-transmitted helminths, two separate cross-sectional epidemiological surveys were carried out in Uganda including 573 and 455 preschool-aged children (≤6 years) living along the shores of Lake Albert and on the islands in Lake Victoria, respectively. Anaemia was found to be a severe public health problem in Lake Albert, affecting 68·9% of children (ninety-five percent confidence intervals (95% CI) 64·9-72·7%), a statistically significant higher prevalence relative to the 27·3% detected in Lake Victoria (95% CI: 23·3-31·7%). After multivariate analysis (controlling for sex and age of the child), the only factor found to be significantly associated with increased odds of anaemia in both lake systems was malaria (Lake Albert, odds ratio (OR)=2·1, 95% CI: 1·4-3·2; Lake Victoria, OR=1·9, 95% CI: 1·2-2·9). Thus intervention strategies primarily focusing on very young children and combating malaria appear to represent the most appropriate use of human and financial resources for the prevention of anaemia in this age group and area. Looking to the future, these activities could be further emphasised within the National Child Health Days(PLUS) agenda.

Point-prevalence recording of the distribution of tropical parasitic diseases at village level is usually sufficient for general monitoring and surveillance. Whilst within-village spatial patterning of diseases exists, and can be important, mapping infected cases in a household-by-household setting is arduous and time consuming. With the development of low-cost GPS-data loggers (< £40) and available GoogleEarth(TM) satellite imagery, we present a field-applicable method based on crowdsourcing for rapid identification of infected cases (intestinal schistosomiasis, malaria and hookworm) by household. A total of 126 mothers with their 247 preschool children from Bukoba village (Mayuge District, Uganda) were examined with half of these mothers given a GPS-data logger to walk home with, returning the unit the same day for data off-loading, after which, households were assigned GPS coordinates. A satellite image of Bukoba was annotated with households denoting the infection status of each mother and child. General prevalence of intestinal schistosomiasis, malaria and hookworm in mothers and children was: 27.2 vs 7.7%, 28.6 vs 87.0% and 60.0 vs 22.3%, respectively. Different spatial patterns of disease could be identified likely representing the intrinsic differences in parasite biology and interplay with human behaviour(s) across this local landscape providing a better insight into reasons for disease micro-patterning., (Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.)

Background: Intestinal schistosomiasis, caused by Schistosoma mansoni, is endemic to Lake Victoria, with high prevalence of the disease observed in human lakeshore communities. However, nonhuman primates have recently been overlooked as potential hosts of the disease, despite known susceptibility., Methods: Using a variety of stool, urine, and serological diagnostic methods, 39 semi-captive wild-born chimpanzees and 37 staff members at Ngamba Island Chimpanzee Sanctuary, Lake Victoria, Uganda, were examined for S. mansoni infection. Miracidia recovered from stool were DNA barcoded to investigate cross-over between humans and chimpanzees. The island was also surveyed for Biomphalaria intermediate host snails, which were examined for infection with S. mansoni., Results: Chimpanzees were unequivocally shown to be infected with intestinal schistosomiasis with a seroprevalence in excess of 90%. Three egg-positive cases were detected, although the sensitivity of the diagnostic tests varied due to earlier prophylactic praziquantel treatment. Miracidia hatched from chimpanzee stool revealed three DNA haplotypes commonly found in humans living throughout Lake Victoria, including staff on Ngamba Island, as well as two novel haplotypes. At one site, a snail was observed shedding schistosome cercariae., Conclusions: The anthropozoonotic potential of intestinal schistosomiasis on Ngamba Island is greater than previously thought. Moreover, the ability of chimpanzees to void schistosome eggs capable of hatching into viable miracidia further suggests that these nonhuman primates may be capable of maintaining a local zoonotic transmission of schistosomiasis independently of humans. The implications for management of captive and wild primate populations at risk of exposure are discussed.

Background: in uganda, control of intestinal schistosomiasis with preventive chemotherapy is typically focused towards treatment of school-aged children; the needs of younger children are presently being investigated as in lakeshore communities very young children can be infected. In the context of future epidemiological monitoring, we sought to compare the detection thresholds of available diagnostic tools for Schistosoma mansoni and estimate a likely age of first infection for these children., Methods and Findings: a total of 242 infants and preschool children (134 boys and 108 girls, mean age 2.9 years, minimum 5 months and maximum 5 years) were examined from Bugoigo, a well-known disease endemic village on Lake Albert. Schistosome antigens in urine, eggs in stool and host antibodies to eggs were inspected to reveal a general prevalence of 47.5% (CI(95) 41.1-54.0%), as ascertained by a positive criterion from at least one diagnostic method. Although children as young as 6 months old could be found infected, the average age of infected children was between 3¼-3¾ years, when diagnostic techniques became broadly congruent., Conclusion: whilst different assays have particular (dis)advantages, direct detection of eggs in stool was least sensitive having a temporal lag behind antigen and antibody methods. Setting precisely a general age of first infection is problematic but if present Ugandan policies continue, a large proportion of infected children could wait up to 3-4 years before receiving first medication. To better tailor treatment needs for this younger ageclass, we suggest that the circulating cathodic antigen urine dipstick method to be used as an epidemiological indicator.

To control intestinal schistosomiasis at a national level in sub-Saharan Africa, there is a need for field-applicable markers to measure morbidity associated with this disease. The purpose of this study was to determine whether fecal calprotectin or fecal occult blood assays could be used as morbidity indicators for intestinal schistosomiasis. The study was carried out in Uganda with a cohort of young children (n = 1,327) and their mothers (n = 726). The prevalence of egg-patent schistosomiasis was 27.2% in children and 47.6% in mothers. No association was found between schistosomiasis infection and fecal calprotectin in children (n = 83, odds ratio [OR] = 1.08, P = 0.881), although an inverse relationship (n = 58, OR = 0.17, P = 0.043) was found in mothers. Fecal occult blood was strongly associated with Schistosoma mansoni infection in children (n = 814, OR = 2.30, P < 0.0001) and mothers (n = 448, OR = 1.95, P = 0.004). Fecal occult blood appears to be useful for measuring morbidity associated with intestinal schistosomiasis and could be used in assessing the impact of control programs upon disease.

Even with a national control programme in place, intestinal schistosomiasis continues to be a major public health problem in school-aged children and other community members in Uganda. This is especially the case in the environments around the Great Lakes, where disease transmission is high, such as Lake Victoria. Moreover, in the most remote areas, some schools might periodically miss large-scale drug administrations owing to inaccessibility. To provide contemporary monitoring and surveillance data, 27 schools along the lakeshore were surveyed with a rapid assessment protocol to determine both prevalence and intensity of Schistosoma mansoni and soil-transmitted helminth infections. In total, 25 (92.6%) of schools were positive for S. mansoni, with an average prevalence across the surveyed children of 42% and average infection intensity of 634 eggs per gram of faeces. Mean prevalence of Trichuris trichiura, Ascaris lumbricoides and hookworm was 12.9%, 9.3% and 2.4%, respectively. Results from questionnaire data revealed a high level of itinerancy among the children, and a total of 38.2% reported to have never received treatment for schistosomiasis, despite 96% living in districts targeted by the national control programme. A birthplace outside of Uganda was a significant predictor for increased risk of schistosomiasis infection (odds ratio (OR) = 9.6), and being resident at a school for less than a year was significantly associated with absence of praziquantel treatment (OR = 0.3). Univariate regression analysis showed a trend of increasing schistosomiasis towards the eastern region of Uganda, while semivariograms of infection prevalence demonstrated a range of spatial autocorrelation of ~78 km. Soil-transmitted helminth infections were more common in the Western region. Our results emphasise how social and demographic variables such as migration may affect epidemiological trends and confound the impact of existing treatment regimes.

Background: Schistosomiasis and soil-transmitted helminthiasis (STH) are among the neglected tropical diseases in Africa. A national control program for these diseases was initiated in Uganda during March 2003. Annual treatment with praziquantel and albendazole was given to schoolchildren in endemic areas and to adults in selected communities where local prevalence of Schistosoma mansoni in schoolchildren was high., Methods: The impact of the treatment program was monitored through cohorts of schoolchildren and adults. Their infection status with S. mansoni and STH was determined by parasitological examinations at baseline and at annual follow-ups. The prevalence and intensity of S. mansoni and STH before and after treatment were analyzed., Results: Two rounds of treatment significantly reduced the prevalence of S. mansoni infection in schoolchildren across three regions in the country from 33.4-49.3% to 9.7-29.6%, and intensity of infection from 105.7-386.8 eggs per gram of faeces (epg) to 11.6-84.1 epg. The prevalence of hookworm infection was reduced from 41.2-57.9% to 5.5-16.1%, and intensity of infection from 186.9-416.8 epg to 3.7-36.9 epg. The proportion of children with heavy S. mansoni infection was significantly reduced from 15% (95% CI 13.4-16.8%) to 2.3% (95% CI 1.6-3.0%). In adults, significant reduction in the prevalence and intensity of S. mansoni and hookworm infections was also observed. More importantly, the prevalence and intensity of both S. mansoni and hookworm infections in the cohorts of newly-recruited 6-year-olds who had never previously received treatment decreased significantly over 2 years: 34.9% (95% CI 31.9-37.8%) to 22.6% (95% CI 19.9-25.2%) and 171.1 epg (95% CI 141.5-200.7) to 72.0 epg (95% CI 50.9-93.1) for S. mansoni; and 48.4% (95% CI 45.4-51.5) to 15.9% (95% CI 13.6-18.2) and 232.7 epg (95% CI 188.4-276.9) to 51.4 epg (95% CI 33.4-69.5) for hookworms, suggesting a general decline in environmental transmission levels., Conclusion: Annual anthelminthic treatment delivered to schoolchildren and to adults at high risk in Uganda can significantly reduce the prevalence and intensity of infection for schistosomiasis and STH, and potentially also significantly reduce levels of environmental transmission of infection.

The objectives of this study were to determine the prevalence and distribution of distended abdomens among Ugandan school children across a range of eco-epidemiological settings and to investigate the relationship between distended abdomens and helminth infections, in particular Schistosoma mansoni, before and 1-year after anthelminthic treatment. A cross-sectional survey was conducted on 4354 school children across eight districts, with a longitudinal 1-year follow-up of 2644 children (60.7%). On both occasions, parasitological, biometrical and clinical data were collected for each child. Baseline prevalence of S. mansoni and hookworms was 44.3% and 51.8%, respectively. Distended abdomens, defined as an abdominal circumference ratio (ACR) >1.05, were observed in 2.5% of the sampled children, several of whom presented with particularly severe distensions necessitating hospital referral. ACR scores were highly overdispersed between districts and schools. Multivariate regression analysis revealed that S. mansoni infection accounted for only a small fraction of ACR variation, suggesting that either single point prevalence and intensity measures failed to reflect this more chronically evolved morbidity and/or that other interacting factors were involved, e.g. malnutrition and malaria. At 1-year follow-up, ACR scores showed an overall trend of regression towards the mean, potentially indicative of amelioration following chemotherapy, but geographic overdispersion still remained.

The potential relationship between Schistosoma mansoni and anemia was examined using data obtained by the Schistosomiasis Control Initiative (SCI) before (baseline) and 1 year after (follow-up) a chemotherapeutic treatment program in Uganda. Changes in hemoglobin (Hb) levels in 2,788 children in relation to their schistosomiasis and/or hookworm infection intensity category and baseline anemia status were analyzed. At baseline, significant predictors of childhood anemia were intensities of S. mansoni and hookworm infection. At follow-up, moderate or heavy hookworm as well as heavy S. mansoni infections were important. Children heavily infected with S. mansoni or hookworm had significantly lower Hb counts at baseline compared with those not infected. Among anemic children at the baseline survey, a significant increase in Hb counts of 0.834 g/dL after treatment was found. Our results suggest that anemia is associated with schistosomiasis and hookworm in Ugandan children and that such anemia shows a significant improvement after chemotherapy.

An evaluation of a commercially available antigen capture dipstick that detects schistosome circulating cathodic antigen (CCA) in urine was conducted in representative endemic areas for intestinal and urinary schistosomiasis in Uganda and Zanzibar, respectively. Under field-based conditions, the sensitivity (SS) and specificity (SP) of the dipstick was 83 and 81% for detection of Schistosoma mansoni infections while positive predictive (PPV) and negative predictive values (NPV) were 84%. Light egg-positive infections were sometimes CCA-negative while CCA-positives included egg-negative children. A positive association between faecal egg output and intensity of CCA test band was observed. Estimating prevalence of intestinal schistosomiasis by school with dipsticks was highly correlated (r=0.95) with Kato-Katz stool examinations, typically within +/-8.5%. In Zanzibar, however, dipsticks totally failed to detect S. haematobium despite examining children with egg-patent schistosomiasis. This was also later corroborated by further surveys in Niger and Burkina Faso. Laboratory testing of dipsticks with aqueous adult worm lysates from several reference species showed correct functioning, however, dipsticks failed to detect CCA in urine from S. haematobium-infected hamsters. While CCA dipsticks are a good alternative, or complement, to stool microscopy for field diagnosis of intestinal schistosomiasis, they have no proven value for field diagnosis of urinary schistosomiasis. At approximately 2.6 US dollars per dipstick, they are presently too expensive to be cost-effective for wide scale use in disease mapping surveys unless Lot Quality Assurance Sampling (LQAS) strategies are developed.

A novel, inexpensive handheld microscope, the Meade Readiview, was evaluated for field diagnosis of intestinal schistosomiasis by comparison of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) against conventional compound microscopy as part of a parasitologic survey in nine sentinel schools and a rapid mapping survey across 22 schools in Uganda. Fecal smears from 685 primary school children were examined and the overall prevalence of Schistosoma mansoni was 45%. However, prevalence by school ranged widely from 0% to 100%. For individual diagnosis the Readiview had a sensitivity of 85%, a specificity of 96%, a PPV of 95%, and an NPV of 88%. Due to the poorer movement control of the glass slide on the Readiview stage, fecal smears with less than four eggs could be overlooked. At the highest magnification (160x), egg-like objects could be confounding. Estimating prevalence by school was usually within +/- 7% of that of conventional microscopy. Since the Readiview is more robust and portable, both in size and weight, and one-tenth as expensive as the traditional compound microscope, a change in the logistics and costs associated with field infection surveillance is possible. This inexpensive microscope is a pragmatic alternative to the compound microscope. It could play an important role in the collection of prevalence data to better guide anthelmintic drug delivery and also empower the diagnostic capacity of peripheral health centers where compound microscopes are few or absent.