Search

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. [ABSTRACT FROM AUTHOR]

Information, behaviors, and technologies spread when people interact. Understanding these interactions is critical for achieving the greatest diffusion of public interventions. Yet, little is known about the performance of starting points (seed nodes) for diffusion. We track routine mass drug administration-the large-scale distribution of deworming drugs-in Uganda. We observe friendship networks, socioeconomic factors, and treatment delivery outcomes for 16,357 individuals in 3491 households of 17 rural villages. Each village has two community medicine distributors (CMDs), who are the seed nodes and responsible for administering treatments. Here, we show that CMDs with tightly knit (clustered) friendship connections achieve the greatest reach and speed of treatment coverage. Importantly, we demonstrate that clustering predicts diffusion through social networks when spreading relies on contact with seed nodes while centrality is unrelated to diffusion. Clustering should be considered when selecting seed nodes for large-scale treatment campaigns. [ABSTRACT FROM AUTHOR]

Background: Repeated mass drug administration (MDA) with preventive chemotherapies is the mainstay of morbidity control for schistosomiasis and soil-transmitted helminths, yet the World Health Organization recently reported that less than one-third of individuals who required preventive chemotherapies received treatment. Methods: Coverage of community-directed treatment with praziquantel (PZQ) and albendazole (ALB) was analyzed in 17 villages of Mayuge District, Uganda. National drug registers, household questionnaires, and parasitological surveys were collected to track 935 individuals before and after MDA. Multilevel logistic regressions, including household and village effects, were specified with a comprehensive set of socioeconomic and parasitological variables. The factors predicting who did not receive PZQ and ALB from community medicine distributors were identified. Results: Drug receipt was correlated among members within a household, and nonrecipients of PZQ or ALB were profiled by household- level socioeconomic factors. Individualswere less likely to receive eitherPZQorALB if they had a Muslimhousehold head or lowhome quality, belonged to the minority tribe, or had settled for more years in their village. Untreated individuals were also more likely to belong to households that did not purify drinking water, had no home latrine, and had no members who were part of the village government. Conclusions: The findings demonstrate howto locate and target individuals who are not treated in MDA. Infection risk factorswere not informative. In particular, age, gender, and occupation were unable to identify non-recipients, althoughWorld Health Organization guidelines rely on these factors. Individuals of low socioeconomic status, minority religions, andminority tribes can be targeted to expandMDA coverage. [ABSTRACT FROM AUTHOR]

Background: The association of anaemia with intestinal schistosomiasis and hookworm infections are poorly explored in populations that are not limited to children or pregnant women. Methods: We sampled 1,832 individuals aged 5–90 years from 30 communities in Mayuge District, Uganda. Demographic, village, and parasitological data were collected. Infection risk factors were compared in ordinal logistic regressions. Anaemia and infection intensities were analyzed in multilevel models, and population attributable fractions were estimated. Findings: Household and village-level predictors of Schistosoma mansoni and hookworm were opposite in direction or significant for single infections. S. mansoni was found primarily in children, whereas hookworm was prevalent amongst the elderly. Anaemia was more prevalent in individuals with S. mansoni and increased by 2.86 fold (p-value<0.001) with heavy S. mansoni infection intensity. Individuals with heavy hookworm were 1.65 times (p-value = 0.008) more likely to have anaemia than uninfected participants. Amongst individuals with heavy S. mansoni infection intensity, 32.0% (p-value<0.001) of anaemia could be attributed to S. mansoni. For people with heavy hookworm infections, 23.7% (p-value = 0.002) of anaemia could be attributed to hookworm. A greater fraction of anaemia (24.9%, p-value = 0.002) was attributable to heavy hookworm infections in adults (excluding pregnant women) as opposed to heavy hookworm infections in school-aged children and pregnant women (20.2%, p-value = 0.001). Conclusion: Community-based surveys captured anaemia in children and adults affected by S. mansoni and hookworm infections. For areas endemic with schistosomiasis or hookworm infections, WHO guidelines should include adults for treatment in helminth control programmes. [ABSTRACT FROM AUTHOR]

Background Over 200,000 people, most of them infected with Schistosoma mansoni inhabit 150 islands in Lake Victoria in Uganda. Although a programme to control the disease has been ongoing since 2003, its implementation in islands is inadequate due to high transport costs on water. In 2011 and 2012, the Global Network for Neglected Tropical Diseases (GNNTD) through Schistosomiasis Control Initiative (SCI) provided financial support to ease treatment delivery on the islands and over the period, therapeutic coverage has been increasing. We conducted a study with an objective to assess community awareness of existence of the disease, its signs, symptoms, causes and transmission as well as attitude, practice and health seeking behavior. Methods This was a cross sectional descriptive study which used pre-tested interviewer administered questionnaire among purposively selected individuals in schools, health facilities and communities. Frequency distribution tables, graphs and cross tabulations were the main forms of data presentation. Results Our results showed that there are numerous challenges that must be overcome to achieve effective control of schistosomiasis in the islands. Many people especially young men are constantly on the move from island to island in search for richer fishing grounds and such groups are commonly known to miss treatment by mass chemotherapy. Unfortunately case management in health facilities is very poor; health facilities are few and understaffed mainly with unskilled personnel who are overburdened by other illnesses such as malaria and HIV and the supply of praziquantel in health facilities is inadequate. Furthermore, sanitation is appalling, no clean water and community knowledge about schistosomiasis is low even among biomedical staff. Conclusion Rather than elimination, our results indicate that the programme should continue to target morbidity control beyond the 2020s until preventive measures have been instituted. The government should provide adequate trained health workers and stock praziquantel in all island health facilities. [ABSTRACT FROM AUTHOR]

Background: Two Kato-Katz thick smears (Kato-Katzs) from a single stool are currently recommended for diagnosing Schistosoma mansoni infections to map areas for intervention. This 'gold standard' has low sensitivity at low infection intensities. The urine point-of-care circulating cathodic antigen test (POC-CCA) is potentially more sensitive but how accurately they detect S. mansoni after repeated praziquantel treatments, their suitability for measuring drug efficacy and their correlation with egg counts remain to be fully understood. We compared the accuracies of one to six Kato-Katzs and one POC-CCA for the diagnosis of S. mansoni in primary-school children who have received zero to ten praziquantel treatments. We determined the impact each diagnostic approach may have on monitoring and evaluation (M&E) and drug-efficacy findings. Method/Principle Findings: In a high S. mansoni endemic area of Uganda, three days of consecutive stool samples were collected from primary school-aged children (six - 12 years) at five time-points in year one: baseline, one-week-post-, four-weeks-post-, six-months-post-, and six-months-one-week-post-praziquantel and three time-points in years two and three: pre-, one-week-post- and four-weeks-post-praziquantel-treatment/retreatment (n = 1065). Two Kato-Katzs were performed on each stool. In parallel, one urine sample was collected and a single POC-CCA evaluated per child at each time-point in year one (n = 367). At baseline, diagnosis by two Kato-Katzs (sensitivity = 98.6%) or one POC-CCA (sensitivity = 91.7%, specificity = 75.0%) accurately predicted S. mansoni infections. However, one year later, a minimum of three Kato-Katzs, and two years later, five Kato-Katzs were required for accurate diagnosis (sensitivity >90%) and drug-efficacy evaluation. The POC-CCA was as sensitive as six Kato-Katzs four-weeks-post and six-months-post-treatment, if trace readings were classified as positive. Conclusions/Significance: Six Kato-Katzs (two/stool from three stools) and/or one POC-CCA are required for M&E or drug-efficacy studies. Although unable to measure egg reduction rates, one POC-CCA appears to be more sensitive than six Kato-Katzs at four-weeks-post-praziquantel (drug efficacy) and six-months-post-praziquantel (M&E). Author Summary: Schistosomiasis is a parasitic disease infecting over 200 million people. It remains a major public health concern despite treatment of over 120 million people in sub-Saharan Africa alone. Accurate diagnostic methods are essential for monitoring drug efficacy and long-term control program success. The World Health Organization recommends two Kato-Katz thick smears (Kato-Katzs) from a single stool for Schistosoma mansoni diagnosis to map prevalence and areas for control interventions. Although highly specific, Kato-Katzs are thought to be insensitive at low egg counts. The recently refined urine point-of-care circulating cathodic antigen test (POC-CCA) has been proposed as a diagnostic alternative for mapping areas for interventions, and potentially for assessing drug efficacy. Over three years we assessed the accuracy of six Kato-Katzs and a single POC-CCA in detecting infections in Ugandan primary-school children at 11 time points with repeated praziquantel treatments. Our results demonstrate that two Kato-Katzs accurately detect S. mansoni infection pre-treatment, but at least three days of two Kato-Katzs per stool or one POC-CCA are required for annual monitoring and treatment evaluation and/or drug-efficacy studies. One POC-CCA may be more sensitive in measuring S. mansoni prevalence than six Kato-Katzs, but its accuracies for rigorous intensity measures are still to be proven. [ABSTRACT FROM AUTHOR]

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. Author Summary: The severity of intestinal schistosomiasis, a disease caused by Schistosoma mansoni infection, is likely under-reported in part due to the scarcity of field-appropriate morbidity markers. Downstream potential complications of this disease include anemia, failure to thrive, and chronic multi-organ damage. Point-of-care (POC) tools to monitor intestinal schistosomiasis in low resource settings are urgently needed to better quantify the burden of disease in endemic countries and to gauge the clinical impact of scale-up of preventive PC. For the present study in rural Uganda, fecal occult blood and fecal calprotectin were identified as potential surrogate markers of intestinal morbidity. We tested both POC tests and found that they were both associated with active schistosomiasis as detected by eggs in stool with significant decrease in test positivity after PZQ treatment demonstrating short term morbidity reversion. Calprotectin was a strong indicator of intestinal inflammation, however, owing to its high per-test price makes it difficult to scale-up accordingly. Conversely, fecal occult blood was technically feasible, low-cost and had optimal performance as a morbidity marker, hence we strongly advocate for its immediate inclusion as a monitoring tool for PC programs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 DaysPLUS agenda. [ABSTRACT FROM PUBLISHER]

Background: To date schistosomiasis control programmes based on chemotherapy have largely aimed at controlling morbidity in treated individuals rather than at suppressing transmission. In this study, a mathematical modelling approach was used to estimate reductions in the rate of Schistosoma mansoni reinfection following annual mass drug administration (MDA) with praziquantel in Uganda over four years (2003–2006). In doing this we aim to elucidate the benefits of MDA in reducing community transmission. Methods: Age-structured models were fitted to a longitudinal cohort followed up across successive rounds of annual treatment for four years (Baseline: 2003, Treatment: 2004–2006; n = 1,764). Instead of modelling contamination, infection and immunity processes separately, these functions were combined in order to estimate a composite force of infection (FOI), i.e., the rate of parasite acquisition by hosts. Results: MDA achieved substantial and statistically significant reductions in the FOI following one round of treatment in areas of low baseline infection intensity, and following two rounds in areas with high and medium intensities. In all areas, the FOI remained suppressed following a third round of treatment. Conclusions/Significance: This study represents one of the first attempts to monitor reductions in the FOI within a large-scale MDA schistosomiasis morbidity control programme in sub-Saharan Africa. The results indicate that the Schistosomiasis Control Initiative, as a model for other MDA programmes, is likely exerting a significant ancillary impact on reducing transmission within the community, and may provide health benefits to those who do not receive treatment. The results obtained will have implications for evaluating the cost-effectiveness of schistosomiasis control programmes and the design of monitoring and evaluation approaches in general. Author Summary: Schistosomiasis is a parasitic disease of enormous public health importance, infecting over 200 million people worldwide, of which the large majority live in sub-Saharan Africa. Control programmes based on the mass treatment of individuals in infected areas with the drug praziquantel have been shown to be successful in reducing the parasite burden and likelihood of developing morbidity in those individuals who receive treatment. Using data from an ongoing intestinal schistosomiasis control programme in Uganda and through the application of a mathematical model, we show that an additional benefit of mass treatment is a decrease in parasite acquisition, via a reduction in the number of transmission stages in the environment. This leads to a lower rate of infection and reinfection of individuals in those areas. We show that this result is valid in areas of differing average infection intensity. The importance of this finding is that this will benefit untreated as well as treated individuals, and will allow a fuller estimation of the benefits of schistosomiasis control programmes. [ABSTRACT FROM AUTHOR]

Background: Intestinal schistosomiasis is often widespread among the populations living around Lake Victoria and on its islands. The Sesse Island group (containing some 84 islands), however, is typically assumed to be a low prevalence zone, with limited transmission, but has never been surveyed in detail. Here, we present a rapid mapping assessment, bringing together snail and parasite information, at 23 sites for the presence of intermediate host snails and at 61 sites for the prevalence of intestinal schistosomiasis in school-aged children (N = 905). Two different diagnostic tools were used and compared at 45 of these sites: Kato-Katz thick faecal smears and circulating cathodic antigen (CCA) urine dipsticks. Results: Biomphalaria snails were found at 11 sites but in low numbers; none was found shedding schistosome cercariae. At 22 out of the 45 sites, local prevalence by urine and/or stool diagnostics was in excess of 50%, although mean prevalence of intestinal schistosomiasis overall was 34.6% (95% confidence intervals (CI) = 31.0- 38.3%) by Kato-Katz and 46.5% (95% CI = 42.7-50.4%) by CCA if 'trace' reactions were considered infection-positive (if considered infection-negative, mean prevalence was 28.1% (95% CI = 24.7-31.7%)). Diagnostic congruence between CCA and Kato-Katz was poor and significant discordance in estimated prevalence by location was found, with each often inferring different mass drug administration regimes. Conclusions: Accurate estimation of schistosome prevalence is important for determining present and future treatment needs with praziquantel; the wide range of schistosome prevalence across the Sesse Island group requires a treatment regime largely tailored to each island. In high prevalence locations, further malacological sampling is required to confirm the extent of local transmission, especially on the northern islands within the group. The observation that different diagnostic tests can provide varying results in terms of estimating prevalence by location, and hence change treatment recommendations, suggests that care must be taken in interpreting raw prevalence data. In particular, further research into the reasons for the differences in the poorer performance of the CCA test should be pursued. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Rapid and accurate identification of communities at highest risk of morbidity from schistosomiasis is key for sustainable control. Although school questionnaires can effectively and inexpensively identify communities with a high prevalence of Schistosoma haematobium, parasitological screening remains the preferred option for S. mansoni. To help reduce screening costs, we investigated the validity of Lot Quality Assurance Sampling (LQAS) in classifying schools according to categories of S. mansoni prevalence in Uganda, and explored its applicability and cost-effectiveness. First, we evaluated several sampling plans using computer simulation and then field tested one sampling plan in 34 schools in Uganda. Finally, cost-effectiveness of different screening and control strategies (including mass treatment without prior screening) was determined, and sensitivity analysis undertaken to assess the effect of infection levels and treatment costs. In identifying schools with prevalences > or =50%, computer simulations showed that LQAS had high levels of sensitivity and specificity (>90%) at sample sizes <20. The method also provides an ability to classify communities into three prevalence categories. Field testing showed that LQAS where 15 children were sampled had excellent diagnostic performance (sensitivity: 100%, specificity: 96.4%, positive predictive value: 85.7% and negative predictive value: 92.3%). Screening using LQAS was more cost-effective than mass treating all schools (US$218 vs. US$482/high prevalence school treated). Threshold analysis indicated that parasitological screening and mass treatment would become equivalent for settings where prevalence > or =50% in 75% of schools and for treatment costs of US$0.19 per schoolchild. We conclude that, in Uganda, LQAS provides a rapid, valid and cost-effective method for guiding decision makers in allocating finite resources for the control of schistosomiasis. [ABSTRACT FROM AUTHOR]

A countrywide description of the distribution of soil-transmitted helminths in Uganda is reported, based on data for 20 185 schoolchildren from 271 schools. The overall prevalence of Ascaris lumbricoides, Trichuris trichiura and hookworm was 6.3%, 5.0% and 43.5%, respectively. The prevalence of A. lumbricoides and T. trichiura was unevenly distributed in the country with prevalence greatest in south-western Uganda whereas hookworm was generally more homogeneously distributed. Based on preliminary cost analysis of an ongoing school-based control programme, the financial delivery cost per schoolchild treated with albendazole is estimated to be between US$ 0.04 and 0.08 in different districts. [ABSTRACT FROM AUTHOR]

Over 1.9 billion individuals require preventive chemotherapy through mass drug administration (MDA). Community-directed MDA relies on volunteer community medicine distributors (CMDs) and their achievement of high coverage and compliance. Yet, it is unknown if village social networks influence effective MDA implementation by CMDs. In Mayuge District, Uganda, census-style surveys were conducted for 16,357 individuals from 3,491 households in 17 villages. Praziquantel, albendazole, and ivermectin were administered for one month in community-directed MDA to treat Schistosoma mansoni , hookworm, and lymphatic filariasis. Self-reported treatment outcomes, socioeconomic characteristics, friendship networks, and health advice networks were collected. We investigated systematically missed coverage and noncompliance. Coverage was defined as an eligible person being offered at least one drug by CMDs; compliance included ingesting at least one of the offered drugs. These outcomes were analyzed as a two-stage process using a Heckman selection model. To further assess if MDA through CMDs was working as intended, we examined the probability of accurate drug administration of 1) praziquantel, 2) both albendazole and ivermectin, and 3) all drugs. This analysis was conducted using bivariate Probit regression. Four indicators from each social network were examined: degree, betweenness centrality, closeness centrality, and the presence of a direct connection to CMDs. All models accounted for nested household and village standard errors. CMDs were more likely to offer medicines, and to accurately administer the drugs as trained by the national control programme, to individuals with high friendship degree (many connections) and high friendship closeness centrality (households that were only a short number of steps away from all other households in the network). Though high (88.59%), additional compliance was associated with directly trusting CMDs for health advice. Effective treatment provision requires addressing CMD biases towards influential, well-embedded individuals in friendship networks and utilizing health advice networks to increase village trust in CMDs. [ABSTRACT FROM AUTHOR]

Highlights: [•] Prevalence and intensity of Schistosoma mansoni by Kato-Katz increased with number of examined smears. [•] Sensitivity of the CCA tests increased with increasing intensity of infections. [•] CCA1 was more sensitive than the Kato-Katz thick smear method. [•] In low levels of infection, no eggs are detected but the CCA1 might still be positive. [•] CCA2 had very low sensitivity and not a good diagnostic tool for S. mansoni in very low endemic settings. [Copyright &y& Elsevier]

In two complementary epidemiological surveys of villages on the Ugandan shoreline of Lake Victoria, the putative occurrence of intestinal schistosomiasis in the local infants (children aged <3 years) was investigated. When, during the first survey, 136 mother-and-infant pairs from a total of 12 villages were studied, only 7% of the infants but 45% of the mothers were found to be egg-patent for Schistosoma mansoni infection. The use of dipstick tests for urine-circulating cathodic antigen indicated, however, a much higher prevalence, of approximately 40%, among the infants. In the second survey, urine samples and multiple, not single, stool samples were collected from another 19 mother-and-infant pairs in two of the 12 study villages (Bugoto and Bwondha), and a standardized questionnaire was implemented. The prevalence of egg-patent infection was then found to be markedly higher in the study infants from Bugoto (86%) than in those from Bwondha (25%). A greater level of mother-and-infant water contact, a higher abundance of (infected) Biomphalaria choanomphala, and an unusual lakeshore topology may explain why S. mansoni infection was so much more common in the Bugoto subjects than in the Bwondha. All but one of the infants studied in the second survey were found to be anaemic (with <110 g haemoglobin/litre). Taken together, these children were less likely to be found infected with hookworm (16%), Hymenolepis nana (11%) or Trichuris trichiura (5%) than with S. mansoni (47%). Infection with the parasites causing intestinal schistosomiasis can be common among the infants living in these lakeshore villages. Although the immediate and later-life clinical impacts of such infection have yet to be elucidated, such infants would probably benefit from regular de-worming. Mothers should be strongly encouraged to visit the nearest health-services clinic, with their infants, for any necessary anthelmintic treatment. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the effects of mass drug administration on Schistosoma mansoni prevalence and associated liver morbidity in treated school-aged children and untreated preschool children., Methods: In April 2008, parasitological (using the Kato-Katz method) and morbidity (determined by portal vein score) data were collected from 263 schoolchildren aged 6 and 7 years. The children had never received praziquantel. In March 2010, following two annual rounds of mass drug administration, 207 children aged 8 and 9 years old were examined to determine the effect of treatment. In addition, 158 untreated 6-year-olds were assessed to compare with the untreated children from 2008., Results: Treatment significantly decreased the prevalence of S. mansoni and associated morbidity in the treated groups. The untreated preschool children also showed a significant decrease in the prevalence of S. mansoni, from 21.1% (2008) to 6.3% (2010) (p<0.001). The percentage of untreated schoolchildren with a normal portal vein score increased significantly from 57.8% (2008) to 70.3% (2010) (p=0.029)., Conclusion: The significantly lower rates of S. mansoni and the decreased liver morbidity in untreated preschool children in 2010 suggest decreased environmental transmission rates and improved liver morbidity in untreated children following several rounds of mass drug administration., (© The Author 2014. 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.)

Urine-dipstick diagnostic tests that detect schistosome circulating cathodic antigen (CCA) have the potential to provide more sensitive and rapid testing for intestinal schistosomiasis in field-based surveys; this is especially so when examining preschool children, from whom it may be difficult to obtain consecutive stool samples. To assess the performance of urine dipsticks, 569 preschool children from four villages along the shore of Lake Albert, Uganda, were screened for Schistosoma mansoni by Kato-Katz (K-K) examination of a single stool sample and CCA urine dipsticks. The prevalence of infection was 32.2% by K-K and 40.0% by CCA tests. Sensitivity and specificity were influenced by whether 'trace' results from the CCA test were characterised as positive or negative for infection with S. mansoni; ambiguities around this issue need to be resolved. Nevertheless, the CCA test showed particular promise for routine epidemiological screening in this setting., (Copyright © 2012 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.)

Preschool children (aged ≤5 years) have so far been overlooked by mass treatment campaigns targeting schistosomiasis, even though praziquantel (PZQ) has been shown to be well tolerated and effective within this age group. The WHO provided the Ugandan Ministry of Health with a syrup formulation of PZQ with the aim of assessing its safety and efficacy in comparison with crushed PZQ tablets for the treatment of intestinal schistosomiasis in preschool children. This study included 1144 preschool children randomly assigned to two treatment arms (PZQ syrup or crushed PZQ tablet) regardless of infection status for direct comparison. Diagnosis of intestinal schistosomiasis was assessed using single stool sample, double Kato-Katz smear examinations. Parasitological cure was assessed 3 weeks after treatment. The observed cure rate was 80.9% for the PZQ syrup arm and 81.7% for the crushed PZQ tablet arm, with egg reduction rates of 86.1% and 89.0%, respectively. Pre-treatment infection intensity was observed to influence cure rates significantly, with cure rates of 88.6% for light infections, 74.5% for moderate infections and 67.4% for heavy infections. No significant difference was found in non-compliance between the PZQ syrup (11.1%) and crushed PZQ tablet (14.7%) arms. PZQ syrup and crushed PZQ tablets have very similar efficacies in the treatment of intestinal schistosomiasis in preschool children., (Copyright © 2012 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.)

Although great reductions in human schistosomiasis have been observed after praziquantel (PZQ) mass drug administration (MDA), some individuals remain infected after multiple treatments. Many MDA programs now require monitoring for drug efficacy as a key component. No molecular tools for PZQ resistance currently exist and investigations into the dose of PZQ required to kill 50% of adult worms in vivo (ED(50)) present ethical, logistical, and temporal restraints. We, therefore, assessed the feasibility and accuracy of a rapid, inexpensive in vitro PZQ test in the laboratory and directly in the field in Uganda under MDA in conjunction with highly detailed infection intensity, clearance, and reinfection data. This test strongly differentiated between subsequently cleared and uncleared infections as well as differences between parasite populations pre- and post-PZQ treatments, advocating its use for on-the-spot monitoring of PZQ efficacy in natural foci. After only a few treatments, uncleared parasites were identified to be phenotypically different from drug-sensitive parasites, emphasizing the urgent need for monitoring of these repeatedly PZQ-treated populations.

Schistosomiasis is widespread in Uganda along large lakes and rivers with approximately 4 million people infected. Hookworm infections also prevalent throughout the country, while infections with Ascaris lumbricoides and Trichuris trichiura are mainly found in south-western Uganda. A national programme aimed at controlling morbidity due to these infections was launched in 2003. This article describes the perceptions, attitudes, constraints and experiences of those implementing the programme and those receiving the treatment. The study used qualitative data collected largely in two districts but also from 18 other districts implementing the programme. Results showed that mass treatment was perceived to be beneficial because the drugs make people feel better. However, side-effects of praziquantel (PZQ), the smell and size of the tablets and the use of height, not weight, to determine dose were raised as major factors discouraging people from taking the drug. Generally, most of the end-users were appreciative of the programme and were beginning to demand regular treatment. Nevertheless, intensive and sustained health education is still vital for improvement of treatment coverage, especially among the non-compliers. It was repeatedly highlighted that there is a need to stock PZQ in all health facilities in endemic areas. Provision of incentives to drug distributors and to involve as many stakeholders as possible in the planning phase were also raised by respondents. Lessons learned for the development and success of a helminth control programme at a national scale are discussed.

Objective: We aimed to assess the health impact of a national control programme targeting schistosomiasis and intestinal nematodes in Uganda, which has provided population-based anthelmintic chemotherapy since 2003., Methods: We conducted longitudinal surveys on infection status, haemoglobin concentration and clinical morbidity in 1871 randomly selected schoolchildren from 37 schools in eight districts across Uganda at three time points - before chemotherapy and after one year and two years of annual mass chemotherapy., Findings: Mass treatment with praziquantel and albendazole led to a significant decrease in the intensity of Schistosoma mansoni - 70% (95% confidence interval (CI): 66-73%) after one year and 82% (95% CI: 80-85%) after two years of treatment. Intensity of hookworm infection also decreased (75% and 93%; unadjusted). There was a significant increase in haemoglobin concentration after one (0.135 g/dL (95% CI: 0.126-0.144)) and two years (0.303 g/dL (95% CI: 0.293-0.312)) of treatment, and a significant decrease in signs of early clinical morbidity. The impact of intervention on S. mansoni prevalence and intensity was similar to that predicted by mathematical models of the impact of chemotherapy on human schistosomiasis. Improvements in haemoglobin concentration were greatest among children who were anaemic or harbouring heavy S. mansoni infection at baseline., Conclusion: Anthelmintic treatment delivered as part of a national helminth control programme can decrease infection and morbidity among schoolchildren and improve haemoglobin concentration.

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.

During the past decade, there has been renewed commitment to programmes for helminth control, and several international initiatives have been launched. Scientific evaluation of large-scale interventions to reduce the incidence of infection and associated morbidity and mortality is vital, not only to demonstrate health benefits, but also to assess cost-effectiveness to show that monies from donor agencies have been used wisely. Using the example of schistosomiasis, this article outlines a framework for the evaluation of the impact of national control programmes, highlighting the important epidemiological and practical issues that must be addressed.

During routine parasitological surveillance and monitoring activities within a National Control Programme for control of human schistosomiasis in Uganda, it was noted that cattle grazing in a water meadow immediately adjacent to Tonya primary school, where the prevalence of intestinal schistosomiasis in children was in excess of 90%, were unusually emaciated. To test the hypothesis that there may have been an anthropozoonotic focus of Schistosoma mansoni within the local herd, a young female heifer, clearly emaciated and c. 8 months old, was slaughtered from which schistosome worms were later recovered by dissection. As female worms inspected by microscopy were not gravid, morphological identification proved inconclusive but analysis of cytochrome oxidase subunit I (COI) and small subunit (SSU) ribosomal DNA sequences from these worms identified them as Schistosoma bovis Sonsino, 1876. This is the first substantiated report of S. bovis from Lake Albert, western Uganda. Further epidemiological surveys are needed to clarify the extent of bovine schistosomiasis within this region, particularly so since this lakeside plain has been earmarked as a future game reserve.