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The Schistosomiasis Consortium for Operational Research (SCORE) was funded in 2008 to improve the evidence base for control and elimination of schistosomiasis—better understanding of the systemic morbidities experienced by children in schistosomiasis-endemic areas and the response of these morbidities to treatment, being essential for updating WHO guidelines for mass drug administration (MDA) in endemic areas. This article summarizes the SCORE studies that aimed to gauge the impact of MDA-based treatment on schistosomiasis-related morbidities. Morbidity cohort studies were embedded in the SCORE’s larger field studies of gaining control of schistosomiasis in Kenya and Tanzania. Following MDA, cohort children had less undernutrition, less portal vein dilation, and increased quality of life in Year 5 compared with baseline. We also conducted a pilot study of the Behavioral Assessment System for Children (BASC-2) in conjunction with the Kenya gaining control study, which demonstrated beneficial effects of treatment on classroom behavior. In addition, the SCORE’s Rapid Answers Project performed systematic reviews of previously available data, providing two meta-analyses related to morbidity. The first documented children’s infection-related deficits in school attendance and achievement and in formal tests of learning and memory. The second showed that greater reductions in egg output following drug treatment correlates significantly with reduced odds of most morbidities. Overall, these SCORE morbidity studies provided convincing evidence to support the use of MDA to improve the health of school-aged children in endemic areas. However, study findings also support the need to use enhanced metrics to fully assess and better control schistosomiasis-associated morbidity.

Schistosoma mansoni infection negatively impacts children's physical health and may influence general well-being. Schistosomiasis control programs aim at reducing morbidity through mass drug administration (MDA). This study aimed to compare morbidity markers between two cohorts of Tanzanian schoolchildren with initial high prevalence of S. mansoni infection. One cohort (N = 254 at baseline) received annual MDA for 4 years using community-wide treatment (CWT). The second cohort (N = 318 at baseline) received school-based treatment (SBT) every other year for 4 years. At year 5, the CWT cohort and the SBT cohort were reduced to 153 and 221 children, respectively. The characteristics of the 198 children lost to follow-up did not differ at baseline from those who were examined in year 5. Schistosoma mansoni infection, hemoglobin (Hb) and anemia, physical fitness, and perceived quality of life were investigated at baseline, year 3, and year 5, whereas liver and spleen pathology (ultrasound) were investigated only at baseline and year 5. Cohorts were compared using two-way mixed-model analysis of variance (ANOVA). Both treatment regimens significantly decreased individual-level mean intensity of S. mansoni infection, anemia, and hepatomegaly, and increased Hb levels after 5 years. Hepatomegaly was the only parameter affected by the treatment regimen as the CWT approach reduced the percentage of individuals with hepatomegaly significantly more than the SBT approach. Both treatment regimens led to reduced physical fitness at year 5 compared with baseline. The modest impact of the two control strategies are probably due to initial low intensity of infection, ensuring low level of schistosomiasis-related morbidity.

The WHO recommends mass treatment with praziquantel as the primary approach for Schistosoma mansoni–related morbidity control in endemic populations. The Schistosomiasis Consortium for Operational Research and Evaluation implemented multi-country, cluster-randomized trials to compare effectiveness of community-wide and school-based treatment (SBT) regimens on prevalence and intensity of schistosomiasis. To assess the impact of two different treatment schedules on S. mansoni–associated morbidity in children, cohort studies were nested within the randomized trials conducted in villages in Kenya and Tanzania having baseline prevalence ≥ 25%. Children aged 7–8 years were enrolled at baseline and followed to ages 11–12 years. Infection intensity and odds of infection were reduced both in villages receiving four years of annual community-wide treatment (CWT) and those who received biennial SBT over 4 years. These regimens were also associated with reduced odds of undernutrition and reduced odds of portal vein dilation at follow-up. However, neither hemoglobin levels nor the prevalence of the rare abnormal pattern C liver scores on ultrasound improved. For the combined cohorts, growth stunting worsened in the areas receiving biennial SBT, and maximal oxygen uptake as estimated by fitness testing scores declined under both regimens. After adjusting for imbalance in starting prevalence between study arms, children in villages receiving annual CWT had significantly greater decreases in infection prevalence and intensity than those villages receiving biennial SBT. Although health-related quality-of-life scores improved in both study arms, children in the CWT villages gained significantly more. We conclude that programs using annual CWT are likely to achieve better overall S. mansoni morbidity control than those implementing only biennial SBT.

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was created to conduct research that could inform programmatic decision-making related to schistosomiasis. SCORE included several large cluster randomized field studies involving mass drug administration (MDA) with praziquantel. The largest of these were studies of gaining or sustaining control of schistosomiasis, which were conducted in five African countries. To enhance relevance for routine practice, the MDA in these studies was coordinated by or closely aligned with national neglected tropical disease (NTD) control programs. The study protocol set minimum targets of at least 90% for coverage among children enrolled in schools and 75% for all school-age children. Over the 4 years of intervention, an estimated 3.5 million treatments were administered to study communities. By year 4, the median village coverage was at or above targets in all studies except that in Mozambique. However, there was often a wide variation behind these summary statistics, and all studies had several villages with very low or high coverage. In studies where coverage was estimated by comparing the number of people treated with the number eligible for treatment, denominator estimation was often problematic. The SCORE experiences in conducting these studies provide lessons for future efforts that attempt to implement strong research designs in real-world contexts. They also have potential applicability to country MDA campaigns against schistosomiasis and other NTDs, most of which are conducted with less logistical and financial support than was available for the SCORE study efforts.

This report summarizes the design and outcomes of randomized controlled operational research trials performed by the Bill & Melinda Gates Foundation–funded Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) from 2009 to 2019. Their goal was to define the effectiveness and test the limitations of current WHO-recommended schistosomiasis control protocols by performing large-scale pragmatic trials to compare the impact of different schedules and coverage regimens of praziquantel mass drug administration (MDA). Although there were limitations to study designs and performance, analysis of their primary outcomes confirmed that all tested regimens of praziquantel MDA significantly reduced local Schistosoma infection prevalence and intensity among school-age children. Secondary analysis suggested that outcomes in locations receiving four annual rounds of MDA were better than those in communities that had treatment holiday years, in which no praziquantel MDA was given. Statistical significance of differences was obscured by a wider-than-expected variation in community-level responses to MDA, defining a persistent hot spot obstacle to MDA success. No MDA schedule led to elimination of infection, even in those communities that started at low prevalence of infection, and it is likely that programs aiming for elimination of transmission will need to add supplemental interventions (e.g., snail control, improvement in water, sanitation and hygiene, and behavior change interventions) to achieve that next stage of control. Recommendations for future implementation research, including exploration of the value of earlier program impact assessment combined with intensification of intervention in hot spot locations, are discussed.

The presence and distribution of various species of canine hookworms in Africa are poorly known. The main objective of this study, therefore, was to identify the hookworm species present in canine faecal samples from Morogoro, Tanzania, using molecular techniques. Faecal samples from 160 local dogs were collected and hookworm positive samples processed to recover larvae for further molecular characterization. DNA was extracted from pools of larvae from individual samples (n = 66), which were analysed subsequently using two different molecular approaches, polymerase chain reaction-linked restriction fragment length polymorphism (PCR-RFLP) and species-specific PCR coupled with Sanger sequencing. The PCR-RFLP technique detected only the presence of the ubiquitousAncylostoma caninumin the 66 samples. However, by species-specific PCR coupled with Sanger sequencing we identified ten samples withA. braziliense, two withUncinaria stenocephalaand five withA. ceylanicum. Thus, all four known species of canine hookworms were identified in Morogoro, Tanzania. To our knowledge this is the first report of the detection of the presence ofU. stenocephalaandA. ceylanicumin Africa using molecular techniques. In addition to their veterinary importance, canine hookworms have zoonotic potential and are of public health concern.

Introduction: Vector control tools are needed to combat leishmaniasis. A semi-synthetic version of a Lutzomyia longipalpis aggregation/sex pheromone (9-methlygermacrene-B) has been developed, and shown efficacy to attract sandflies in the lab and to chicken sheds in the field. Here, we present results from a cluster-randomised trial performed in Brazil where we test the efficacy of the pheromone deployed with insecticide, a novel lure-and-kill intervention, to reduce leishmaniasis transmission to the canine reservoir. Aim: Investigate the efficacy of sandfly sex pheromone baited + insecticide treated chicken roosts to reduce transmission of Leishmania infantum among the reservoir population (dogs). Methods: We conducted a cluster-randomised trial across 42 communities in Brazil. Pheromone lures plus insecticide were applied in 14 communities, and outcomes compared to that of 28 other communities that received either a placebo (sham lure + insecticide) or deltamethrin-impregnated collars fitted to dogs. We quantify the primary intervention effects by comparison of the number of uninfected dogs that seroconverted in each arm over the course of the 2-year trial. Results: A reduction in canine incidence is attributed to the pheromone + insecticide intervention, which is consistent across the levels of hierarchical analysis, though the errors are broad. The performance of the pheromone followed similar patterns as the collar arm which significantly reduced seroconversion incidence. Conclusion: These data represent the first trial of a synthetic vector pheromone applied in public health control, and the first cluster-randomised trial of dog collars in Brazil. Both methods show potential for the control of zoonotic visceral leishmaniasis in the Americas; developments of the pheromone lure-and-kill strategy are underway.

This report summarizes the design and outcomes of randomized controlled operational research trials performed by the Bill & Melinda Gates Foundation-funded Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) from 2009 to 2019. Their goal was to define the effectiveness and test the limitations of current WHO-recommended schistosomiasis control protocols by performing large-scale pragmatic trials to compare the impact of different schedules and coverage regimens of praziquantel mass drug administration (MDA). Although there were limitations to study designs and performance, analysis of their primary outcomes confirmed that all tested regimens of praziquantel MDA significantly reduced local Schistosoma infection prevalence and intensity among school-age children. Secondary analysis suggested that outcomes in locations receiving four annual rounds of MDA were better than those in communities that had treatment holiday years, in which no praziquantel MDA was given. Statistical significance of differences was obscured by a wider-than-expected variation in community-level responses to MDA, defining a persistent hot spot obstacle to MDA success. No MDA schedule led to elimination of infection, even in those communities that started at low prevalence of infection, and it is likely that programs aiming for elimination of transmission will need to add supplemental interventions (e.g., snail control, improvement in water, sanitation and hygiene, and behavior change interventions) to achieve that next stage of control. Recommendations for future implementation research, including exploration of the value of earlier program impact assessment combined with intensification of intervention in hot spot locations, are discussed.

Schistosoma mansoni infection negatively impacts children’s physical health and may influence general well-being. Schistosomiasis control programs aim at reducing morbidity through mass drug administration (MDA). This study aimed to compare morbidity markers between two cohorts of Tanzanian schoolchildren with initial high prevalence of S. mansoni infection. One cohort (N = 254 at baseline) received annual MDA for 4 years using community-wide treatment (CWT). The second cohort (N = 318 at baseline) received school-based treatment (SBT) every other year for 4 years. At year 5, the CWT cohort and the SBT cohort were reduced to 153 and 221 children, respectively. The characteristics of the 198 children lost to follow-up did not differ at baseline from those who were examined in year 5. Schistosoma mansoni infection, hemoglobin (Hb) and anemia, physical fitness, and perceived quality of life were investigated at baseline, year 3, and year 5, whereas liver and spleen pathology (ultrasound) were investigated only at baseline and year 5. Cohorts were compared using two-way mixed-model analysis of variance (ANOVA). Both treatment regimens significantly decreased individual-level mean intensity of S. mansoni infection, anemia, and hepatomegaly, and increased Hb levels after 5 years. Hepatomegaly was the only parameter affected by the treatment regimen as the CWT approach reduced the percentage of individuals with hepatomegaly significantly more than the SBT approach. Both treatment regimens led to reduced physical fitness at year 5 compared with baseline. The modest impact of the two control strategies are probably due to initial low intensity of infection, ensuring low level of schistosomiasis-related morbidity.

In July 2013, the Department of Paediatric and Adolescent Medicine at Østfold Hospital Trust introduced nitrous oxide as an option for procedural sedation of children and adolescents.During the period 13 July 2013-25 August 2017, 311 procedures were performed with nitrous oxide in 238 patients aged 4-17 years. Age, sex, type and duration of procedure, any supplementary medications, complications and whether the procedure would previously have required general anaesthesia, were recorded in a form. The child rated the effectiveness of nitrous oxide using a graded age-appropriate 10-point pain scale, and the nurse rated it as good, moderate or none.The children reported a median pain score of 2/10 (interquartile range 0-4), and nurses rated effectiveness as good in 247 of 304 (81 %) cases. For 43 % of procedures, the nurse felt that general anaesthesia would have been necessary had the department not had access to nitrous oxide. Adverse effects, most often dizziness, were reported in 110 of 311 procedures (35 %). In 7 of 311 procedures (2 %), the patient experienced adverse effects that resulted in stoppage of the procedure. The procedure was completed in 286 (92 %) children.Nitrous oxide is a useful option for children who require procedural sedation, and means that more procedures can be performed without general anaesthesia.

There is a need for diagnostic techniques which are sensitive, specific, rapid and easy to perform at the point-of-care. The aim of this study was to evaluate the diagnostic performance of the Circulating Cathodic Antigen (POC-CCA) assay for Schistosoma mansoni in four schools along the coast of Lake Victoria in Mwanza Region, Tanzania, and to optimize the reading of the POC-CCA test lines by using a computer software image analysis. Initially, a pilot study in 106 school children indicated that time of urine collection did not have an impact on CCA results as 84.9% (90) had identical scores from a urine collected in the morning and a urine taken at midday after drinking 0.5L of water. The main study was conducted among 404 school children (aged 9–12years) where stool and urine samples were collected for three consecutive days. For S. mansoni diagnosis, stool samples were examined for eggs with duplicate Kato-Katz smears, whereas urine samples were tested for presence of antigen by POC-CCA. The proportion of positive individuals for S. mansoni by one POC-CCA was higher compared to two Kato-Katz smears (66.1% vs. 28.7%; p

SummaryA majority of Zambian children live in impoverished communities that lack safe water and proper sanitation, exposing them to urogenital and intestinal helminths. Efforts to mitigate this plight have been implemented through mass drug administration aimed at deworming school-age and under-five children against schistosomiasis and soil-transmitted helminths. However, the disease status of adults living in the same communities as the treated children remains unknown. The aim of this study was to describe the potential contribution of infected adult populations to the transmission of these infections in southern Zambia. A cross-sectional study was conducted in April and May 2013 as part of baseline survey for a larger study in Mazabuka and Siavonga Districts. Stool and urine samples of 2829 adults from five catchment areas were collected and processed using Kato-Katz and urine filtration methods, respectively. Adults from Siavonga had a 13.9% combined prevalence ofSchistosoma haematobiumandS. mansoni, and 12.1% combined prevalence ofAscaris lumbricoidesand hookworm. There was noS. mansoniin Mazabuka, and only a 5.3% prevalence ofS. haematobiumand 7.4% combined prevalence ofA. lumbricoidesand hookworm. Additionally, noTrichuris trichiurainfections were observed in the two districts. Despite most of these infections being categorized as light intensity, heavy infection intensities were also found for all four parasite species. If this infected adult population is left untreated, the possibility of it acting as a reservoir of infections and ultimately transmitting the infections to treated children remains. Therefore, there is need to consider alternative treatment strategies that incorporate adults, thereby reducing the risk of contaminating the environment and perpetuating transmission to children.

Schistosomiasis is a waterborne, infectious disease with high morbidity and significant economic burdens affecting more than 250 million people globally. Disease control has, with notable success, for decades focused on drug treatment of infected human populations, but a recent paradigm shift now entails moving from control to elimination. To achieve this ambitious goal more sensitive diagnostic tools are needed to monitor progress towards transmission interruption in the environment, especially in low-intensity infection areas. We report on the development of an environmental DNA (eDNA) based tool to efficiently detect DNA traces of the parasite Schistosoma mansoni directly in the aquatic environment, where the non-human part of the parasite life cycle occurs. To our knowledge, this is the first report of the successful detection of S. mansoni in freshwater samples using aquatic eDNA. True eDNA was detected in as few as 10 cercariae/L water in laboratory experiments. The field applicability of the method was tested at known transmission sites in Kenya, where comparison of schistosome detection by conventional snail surveys (snail collection and cercariae shedding) with eDNA (water samples) showed 71% agreement between the methods. The eDNA method furthermore detected schistosome presence at two additional sites where snail shedding failed, demonstrating a higher sensitivity of eDNA sampling. We conclude that eDNA provides a promising new tool to significantly improve the environmental surveillance of S. mansoni. Given the proper method and guideline development, eDNA could become an essential future component of the schistosomiasis control tool box needed to achieve the goal of elimination.SignificanceAccurate detection and delineation of schistosomiasis transmission sites will be vital in on-going efforts to control and ultimately eliminate one of the most neglected tropical parasitic diseases affecting more than 250 million people worldwide. Conventional methods to detect parasites in the environment are cumbersome and have low sensitivity. We therefore developed an environmental DNA (eDNA) based method for schistosome detection in aquatic environments. Aquatic eDNA showed higher sensitivity than conventional snail surveys. We conclude that eDNA is a promising non-invasive and sensitive tool for environmental surveillance of schistosomiasis transmission. As the efforts and aims to control the disease are transitioning towards complete transmission interruption, this could be the robust and cost-effective surveillance tool needed in the “end game” of schistosomiasis.

Background In July 2013, the Department of Paediatric and Adolescent Medicine at Ostfold Hospital Trust introduced nitrous oxide as an option for procedural sedation of children and adolescents. Material and method During the period 13 July 2013-25 August 2017, 311 procedures were performed with nitrous oxide in 238 patients aged 4-17 years. Age, sex, type and duration of procedure, any supplementary medications, complications and whether the procedure would previously have required general anaesthesia, were recorded in a form. The child rated the effectiveness of nitrous oxide using a graded age-appropriate 10-point pain scale, and the nurse rated it as good, moderate or none. Results The children reported a median pain score of 2/10 (interquartile range 0-4), and nurses rated effectiveness as good in 247 of 304 (81 %) cases. For 43 % of procedures, the nurse felt that general anaesthesia would have been necessary had the department not had access to nitrous oxide. Adverse effects, most often dizziness, were reported in 110 of 311 procedures (35 %). In 7 of 311 procedures (2 %), the patient experienced adverse effects that resulted in stoppage of the procedure. The procedure was completed in 286 (92 %) children. Interpretation Nitrous oxide is a useful option for children who require procedural sedation, and means that more procedures can be performed without general anaesthesia.

Schistosomiasis is a water-based, infectious disease with high morbidity and significant economic burdens affecting >250 million people globally. Disease control has, with notable success, for decades focused on drug treatment of infected human populations, but a recent paradigm shift now entails moving from control to elimination. To achieve this ambitious goal, more sensitive diagnostic tools are needed to monitor progress toward transmission interruption in the environment, especially in low-intensity infection areas. We report on the development of an environmental DNA (eDNA)-based tool to efficiently detect DNA traces of the parasite Schistosoma mansoni directly in the aquatic environment, where the nonhuman part of the parasite life cycle occurs. This is a report of the successful detection of S. mansoni in freshwater samples by using aquatic eDNA. True eDNA was detected in as few as 10 cercariae per liter of water in laboratory experiments. The field applicability of the method was tested at known transmission sites in Kenya, where comparison of schistosome detection by conventional snail surveys (snail collection and cercariae shedding) with eDNA (water samples) showed 71% agreement between the methods. The eDNA method furthermore detected schistosome presence at two additional sites where snail shedding failed, demonstrating a higher sensitivity of eDNA sampling. We conclude that eDNA provides a promising tool to substantially improve the environmental surveillance of S. mansoni. Given the proper method and guideline development, eDNA could become an essential future component of the schistosomiasis control tool box needed to achieve the goal of elimination.

Annual school-based mass drug administration with praziquantel has been widely implemented to control schistosomiasis, but other treatment strategies could have a different impact. The aim of this study was to investigate the impact of six different treatment strategies on Schistosoma mansoni infection in a cluster-randomized controlled trial in schoolchildren, in a high transmission area of the Mwanza Region, Tanzania. A total of 150 villages were randomized into six arms with 25 villages in each arm. In each village, approximately 100 schoolchildren aged 9–12 years were randomly selected each year and investigated for S. mansoni prevalence and intensity based on three consecutive stool samples using the duplicate Kato–Katz technique. Four years of community-wide treatment (CWT) was the most intensive treatment strategy, whereas 2 years of school-based treatment (SBT) combined with 2 years without treatment (holiday) was the least intensive treatment. The remaining strategies constituted different combinations of CWT, SBT, and holiday years. Baseline results on S. mansoni infection were obtained from 14,620 schoolchildren from 148 villages, and mean prevalence and mean intensity among infected were 48.6–60.6% and 130.5–229.8 eggs per gram, respectively. Over the years, mean prevalence and mean intensities declined in all arms, but when comparing year 5 mean prevalence and mean intensity, there were no statistically significant differences between treatment arms. Thus, measured in a random selection of schoolchildren aged 9–12 years, four times CWT was not superior to four times SBT, while 2 years of treatment holiday combined with 2 years of SBT had the same impact as 4 years of SBT.

Avian schistosomes are widespread parasites of snails and waterfowl and may cause cercarial dermatitis (swimmer's itch) in humans, a disease that is frequently reported in European countries. These parasites are known to occur in Denmark, but here, we applied a new approach using molecular tools to identify the parasites at species level. In order to do that, 499 pulmonate freshwater snails (Radix sp., Lymnaea stagnalis, Stagnicola sp. and Planorbarius corneus) were sampled from 12 lakes, ponds, and marshes in the greater Copenhagen area. Avian schistosome cercariae were identified by microscopy and subjected to molecular investigation by sequencing and phylogenetic analysis of the 5.8S and ITS2 ribosomal DNA for species identification. Additionally, snail hosts belonging to the genus Radix were identified by sequencing and phylogenetic analysis of partial ITS2 ribosomal DNA. Three out of 499 snails shed different species of Trichobilharzia cercariae: Trichobilharzia szidati was isolated from L. stagnalis, Trichobilharzia franki from Radix auricularia and Trichobilharzia regenti from Radix peregra. In the light of the public health risk represented by bird schistosomes, these findings are of concern and, particularly, the presence of the potentially neuro-pathogenic species, T. regenti, in Danish freshwaters calls for attention.

Although pigs are commonly infected with Cryptosporidium spp. and Giardia duodenalis, including potentially zoonotic species or genotypes, little is known about age-related infection levels, seasonal differences and genetic variation in naturally infected pigs raised in organic management systems. Therefore, the current study was conducted to assess seasonal and age-related variations in prevalence and infection intensity of Cryptosporidium and Giardia, evaluate zoonotic potential and uncover correlations between species/genotypes, infection intensity and faecal consistency. Shedding of oocysts and cysts ((oo-)cysts) was monitored at quarterly intervals (September 2011-June 2012) in piglets (n = 152), starter pigs (n = 234), fatteners (n = 230) and sows (n = 240) from three organic farms in Denmark. (oo-)Cysts were quantified by immunofluorescence microscopy; and 56/75 subsamples from Cryptosporidium infected pigs were successfully analysed by PCR amplification and partial sequencing of the small subunit (SSU) 18S rRNA and hsp70genes, while 13/67 Giardia subsamples were successfully analysed by amplification and partial sequencing of the 18S rRNA and the gdh genes. Altogether, Cryptosporidium or Giardia infections were observed in 40.9% (350/856) and 14.0% (120/856) of the pigs, respectively, including 8.2% (70/856) infected with both parasites. Prevalence, intensity of infections and presence of Cryptosporidium species varied significantly between age-groups; 53.3% piglets, 72.2% starter pigs, 40.4% fatteners and 2.9% sows were infected with Cryptosporidium, whereas 2.0% piglets, 27.4% starter pigs, 17.8% fatteners and 5.0% sows were infected with Giardia. The overall prevalence was stable throughout the year, except for dual-infections that were more prevalent in September and December (p < 0.05). The infection intensity was age-related for both parasites, and dual-infected pigs tended to excrete lower levels of oocysts compared to pigs harbouring only Cryptosporidium. Likewise, pigs infected with Cryptosporidium scrofarum excreted fewer oocysts (mean CPG: 54,848 ± 194,508CI: 9085-118,781) compared to pigs infected with Cryptosporidium suis (mean OPG: 351,035 ± 351,035CI: 67,953-634,117). No correlation between faecal consistency and (oo-)cyst excretion levels was observed. Of the successfully genotyped isolates, 38/56 (67.9%) were C. scrofarum and 18/56 (32.1%) were C. suis, while the livestock specific G. duodenalis Assemblage E was detected in 11/13 (84.6%) isolates and the potentially zoonotic Assemblage A was identified in 2/13 (15.4%) isolates. Piglets exclusively hosted C. suis, with one exception, while starter pigs and fatteners predominantly hosted C. scrofarum. As organic pigs are partly reared outdoors, environmental contamination with Cryptosporidium and Giardia is inevitable. Nevertheless, the present data indicate that the potential public health risk associated with both of these parasites in Danish organic pig production seems to be negligible.

Objective:When caring for a loved one with a life-limiting illness, a caregiver's own physical, emotional, and spiritual suffering can be profound. While many interventions focus on physical and emotional well-being, few caregiver interventions address existential and spiritual needs and the meaning that caregivers ascribe to their role. To evaluate the feasibility and acceptability of the process and content of Caregiver Outlook, we employed a manualized chaplain-led intervention to improve well-being by exploring role-related meaning among caregivers of patients with a life-limiting illness.Method:We conducted a single-arm pre–post pilot evaluation among caregivers of patients with advanced cancer or amyotrophic lateral sclerosis (ALS). Caregivers completed three chaplain-led intervention sessions focusing on (1) a relationship review, (2) forgiveness, and (3) legacy. Outcomes administered at baseline and at 1 and 2 weeks after the intervention included quality of life, anxiety, depression, spiritual well-being, religious coping, caregiver burden, and grief.Results:The sample (N = 31) included a range of socioeconomic status groups, and the average age was approximately 60 years. A third of them worked full-time. Some 74% of our participants cared for a spouse or partner, and the other quarter of the sample cared for a parent (13%), child (10%), or other close family member (3%). At baseline, participants did not demonstrate clinical threshold levels of anxiety, depression, or other indicators of distress. Outcomes were stable over time. The qualitative results showed the ways in which Caregiver Outlook was assistive: stepping back from day-to-day tasks, the opportunity to process emotions, reflecting on support received, provoking thoughts and emotions between sessions, discussing role changes, stimulating communication with others, and the anonymity of a phone conversation. Both religious and nonreligious participants were pleased with administration of the chaplain intervention.Significance of results:The acceptability and feasibility of Caregiver Outlook were demonstrated among caregivers of patients with an advanced illness. Our pilot findings suggest minor modifications to study participant screening, interventionist guidance, and the study measures.

Intestinal parasitic infections are common among children worldwide. This study was aimed at determining risk factors for infection with soil transmitted helminths, Cryptosporidium spp., and Giardia duodenalis, among children in preschools. The study was in two parts: a cross-sectional study in which data were collected from 403 children from 10 preschools and a longitudinal study in which 100 children from four preschools from the previous 10 were selected. Prevalence of Ascaris lumbricoides was 12.0%, while that of hookworm was 8.3%. Overall prevalence of Cryptosporidium and G. duodenalis was 28.0% and 29.0%, respectively. Low education level of parent/guardian was a significant risk factor for A. lumbricoides (OR = 2.35, 95% CI: 1.02–5.41; P=0.04), while roofing types other than corrugated iron sheets were found to be protective for G. duodenalis infection in both bivariate and multivariate analyses (multivariate: OR = 0.67, 95% CI: 0.45–0.99; P=0.04). Low socioeconomic level was found to be protective for Cryptosporidium spp. infection in multivariate analysis (OR = 0.59, 95% CI: 0.35–0.99; P=0.04). In the longitudinal study, none of the factors were associated with either infection. These findings may have implications for other preschools in other districts in Zambia.

Schistosomiasis, a disease caused by Schistosoma trematode parasites, affects hundreds of millions of people and accounts for more than 40% of the global health burden due to neglected tropical diseases. In Uganda, intestinal schistosomiasis is endemic in 73 out of 112 districts and about 55% of the population of 36 million individuals are at risk. There is scanty information on the status and burden of schistosomiasis in preschool children less than six years of age in Uganda. This study aimed to assess the status of Schistosoma mansoni infections in children aged 1-5 years in Uganda. S. mansoni prevalence and intensity of infection were examined in 3058 children from 5 districts along Lake Victoria shoreline, eastern Uganda. For each child one stool sample was collected on three consecutive days. The Kato-Katz technique was used to prepare stool smears on slides for microscopic examination. Short interviews with a standardized pre-tested questionnaire prepared in the local language (Lusoga) were administered to each caregiver to identify risk factors associated with S. mansoni infection. An overall S. mansoni prevalence of 39.3% (95% CI: 38.0-41.1%) was estimated out of the 3058 stool samples examined. The geometric mean intensity of S. mansoni among the infected children was 273 (95% CI: 241-305) eggs per gram of faeces. Both prevalence and intensity of infection increased linearly with age (P

Preventive chemotherapy with praziquantel for schistosomiasis morbidity control is commonly done by mass drug administration (MDA). MDA regimen is usually based on prevalence in a given area, and effectiveness is evaluated by decreases in prevalence and/or intensity of infection after several years of implementation. Multiple studies and programs now find that even within well-implemented, multiyear, annual MDA programs there often remain locations that do not decline in prevalence and/or intensity to expected levels. We term such locations “persistent hotspots.” To study and address persistent hotspots, investigators and neglected tropical disease (NTD) program managers need to define them based on changes in prevalence and/or intensity. But how should the data be analyzed to define a persistent hotspot? We have analyzed a dataset from an operational research study in western Tanzania after three annual MDAs using four different approaches to define persistent hotspots. The four approaches are 1) absolute percent change in prevalence; 2) percent change in prevalence; 3) change in World Health Organization guideline categories; 4) change (absolute or percent) in both prevalence and intensity. We compare and contrast the outcomes of these analyses. Our intent is to show how the same dataset yields different numbers of persistent hotspots depending on the approach used to define them. We suggest that investigators and NTD program managers use the approach most suited for their study or program, but whichever approach is used, it should be clearly stated so that comparisons can be made within and between studies and programs.

Soil-transmitted helminths of the genus Strongyloides (S. fuelleborni and the more prevalent S. stercoralis) are currently believed to infect an estimated 30-100 million people worldwide. The health consequences of S. stercoralis infections range from asymptomatic light infections to chronic symptomatic strongyloidiasis. Uncontrolled multiplication of the parasite (hyperinfection) and potentially life-threatening dissemination of larvae to all internal organs is found among individuals with compromised immune system functions. This paper provides an overview of the current state of the art in relation to diagnostic methods for detecting the infection, the morbidity caused by the infection and the recommended treatment. It further discusses some of the reasons why this infection is so neglected and the consequence of this for the estimated global prevalence. The paper finally points to the gaps in our knowledge and future research needs related to this infection. As Strongyloides infections have the potential to develop into severe disease in certain population subgroups, untreated infections could cause serious problems in the community. Therefore, we need to carefully investigate this parasite in order to develop and implement effective control programmes.

SummaryDespite attempts to control intestinal schistosomiasis through school-based mass drug administration (MDA) with praziquantel using school teachers in Uganda, less than 30% of the school children take the treatment in some areas. The aim of the study was to understand why the uptake of praziquantel among school children is low and to suggest strategies for improved uptake. This was a cross-sectional qualitative study in which 24 focus group discussions and 15 key informant interviews were conducted 2 months after MDA. The focus group discussions were held with school children in twelve primary schools and the key informant interviews were held with school teachers, sub-county health assistants and the District Vector Control Officer. The study shows that the low uptake of praziquantel among school children is a result of a complex interplay between individual, interpersonal, institutional, community and public policy factors. The individual and interpersonal factors underpinning the low uptake include inadequate information about schistosomiasis prevention, beliefs and attitudes in the community about treatment of schistosomiasis and shared concerns among children and teachers about the side-effects of praziquantel, especially when the drug is taken on an empty stomach. The institutional, policy and community factors include inadequate preparation and facilitation of teachers and the school feeding policy, which requires parents to take responsibility for providing their children with food while at school, yet many parents cannot meet the cost of a daily meal due to the prevailing poverty in the area. It is concluded that strategies to improve uptake of praziquantel among school children need to be multi-pronged addressing not only the preparation and motivation of teachers and health education for children, but also the economic and political aspects of drug distribution, including the school feeding policy.

Graphical abstract, Highlights • The low uptake of FBZ by Trichuris suis in vitro was confirmed in vivo in pigs. • High correlation between plasma and worm concentrations of OXF and FBZSO2. • No correlation between plasma and worm concentrations of FBZ. • The blood–enterocyte pathway seems important for FBZ-metabolites to reach T. suis. • FBZ may enter T. suis from the blood–enterocyte pathway and the intestinal content., It is recognized that the clinical efficacy of single dose benzimidazoles (BZs) against the nematode, Trichuris suis of pigs and the closely related Trichuris trichiura in humans is only poor to moderate. Recent in vitro studies have indicated that a low uptake of fenbendazole (FBZ) in T. suis may be responsible for its poor efficacy. The aim of this study was to investigate this hypothesis by measuring the concentrations of FBZ and its metabolites, oxfendazole (OXF) and FBZ sulphone (FBZSO2), in T. suis isolated from FBZ treated pigs and in plasma of the pigs. The highest concentration of FBZ measured in T. suis was 66.6 pmol/mg dry worm tissue which was approximately half of what was measured in a previous in vitro study. The correlation between drug concentrations in plasma and in T. suis worms was highly positive for OXF (r = 0.93, P = 0.0007) and FBZSO2 (r = 0.85, P = 0.007), but no correlation was found for FBZ. This study shows that the low uptake of FBZ observed for T. suis in vitro, also takes place in vivo. The high and significant correlations between OXF and FBZSO2 concentrations in plasma of the pigs and T. suis (and the lack of this correlation for FBZ) suggests that the metabolites reach the worms via the blood–enterocyte interface while FBZ primarily reaches the worms via the intestinal lumen of the host.

In rural areas of Zambia primary health care is provided by rural health centres (RHCs). However, accessibility to these services is limited. In the catchment areas of two RHCs in Mazabuka district (Chivuna and Magoye RHCs) we investigated factors that caretakers perceived as barriers to health care for under five children and how they cope with the barriers. Ten Focus Group Discussions (FGDs) with caretakers of children under-five years of age and key informant interviews with six health workers from the two RHCs, and eight community health workers were conducted in May 2006. The major factors perceived as barriers were poor quality of health services, unavailability of medicines, financial constraints, weak outreach programmes, bad scheduling of health programmes, poor communication, long distance to RHCs and low awareness levels of the importance of taking children for child health week among caretakers. Caretakers’ main coping strategy was the use of the folk sector of health care. The findings of this study highlight the challenges that exist in accessing of health care in resource-poor settings and underscore that the provision of health care services of good quality remains a major challenge.

Background: The benefits of integrated control of malaria, schistosomiasis, and soil-transmitted helminth infections have not been fully explored in Ghanaian schoolchildren.Objective: To assess the impact of co-administered artemether-lumefantrine plus albendazole, and artemether-lumefantrine plus albendazole plus praziquantel compared to albendazole plus praziquantel on anaemia, sustained attention, and recall in schoolchildren.Design: This three-arm, open-label intervention study was carried out in Ghana among class three schoolchildren. Artemether-lumefantrine and albendazole were co-administered to 131 schoolchildren in Study Arm 1; artemether-lumefantrine, albendazole, and praziquantel to 90 children in Study Arm 2 versus albendazole and praziquantel to 127 children in Control Arm 3. Medicines were administered to all children at least 30 min after a meal. A HemoCue® photometer was used to measure haemoglobin (Hb), while the code transmission test (CTT), adapted from the Test of Everyday Attention for Children (TEA-Ch), was used to measure sustained attention and recall before-and-after interventions in June 2011 and June 2012.Results: We observed significant malaria parasite prevalence reductions of 62.8 and 59.2% in Study Arm 1 from 24.2 to 9.0%, p0.05). Meanwhile, anaemia prevalence reduced significantly (p

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was established in 2008 to answer strategic questions about schistosomiasis control. For programme managers, a high-priority question is: what are the most cost-effective strategies for delivering preventive chemotherapy (PCT) with praziquantel (PZQ)? This paper describes the process SCORE used to transform this question into a harmonized research protocol, the study design for answering this question, the village eligibility assessments and data resulting from the first year of the study. Beginning in 2009, SCORE held a series of meetings to specify empirical questions and design studies related to different schedules of PCT for schistosomiasis control in communities with high (gaining control studies) and moderate (sustaining control studies) prevalence of Schistosoma infection among school-aged children. Seven studies are currently being implemented in five African countries. During the first year, villages were screened for eligibility, and data were collected on prevalence and intensity of infection prior to randomisation and the implementation of different schemes of PZQ intervention strategies. These studies of different treatment schedules with PZQ will provide the most comprehensive data thus far on the optimal frequency and continuity of PCT for schistosomiasis infection and morbidity control. We expect that the study outcomes will provide data for decision-making for country programme managers and a rich resource of information to the schistosomiasis research community. The trials are registered at International Standard Randomised Controlled Trial registry (identifiers: ISRCTN99401114 , ISRCTN14849830 , ISRCTN16755535 , ISRCTN14117624 , ISRCTN95819193 and ISRCTN32045736 ).

The potential for the transport of viable Cryptosporidium parvum oocysts through soil to land drains and groundwater was studied using simulated rainfall and intact soil columns which were applied raw slurry or separated liquid slurry. Following irrigation and weekly samplings over a 4-week period, C. parvum oocysts were detected from all soil columns regardless of slurry type and application method, although recovery rates were low (r = 0.63) with the total number of oocysts found. Destructively sampling of the soil columns showed that type of slurry and irrigation played a role in the vertical distribution of oocysts, with more oocysts recovered from soil columns added liquid slurry irrespective of the irrigation status. Further studies are needed to determine the effectiveness of different slurry separation technologies to remove oocysts and other pathogens, as well as whether the application of separated liquid slurry to agricultural land may represent higher risks for groundwater contamination compared to application of raw slurry.

The whipworms Trichuris trichiura and Trichuris suis in humans and pigs, respectively, are believed to be two different species yet closely related. Morphologically, adult worms, eggs and larvae of the two species are indistinguishable. The aim of this study was to examine the genetic variation of Trichuris sp. mainly recovered from natural infected pigs and humans. Worm material isolated from humans and pigs living in the same geographical region in Uganda were analyzed by PCR, cloning and sequencing. Measurements of morphometric characters were also performed. The analysis of the ITS-2 (internal transcribed spacer) region showed a high genetic variation in the human-derived worms with two sequence types, designated type 1 and type 2, differing with up to 45%, the type 2 being identical to the sequence found in pig-derived worms. A single human-derived worm showed exclusively the type 2-genotype (T. suis-type) and three cases of 'heterozygote' worms in humans were identified. However, the analysis showed that sympatric Trichuris primarily assorted with host origin. Sequence analysis of a part of the genetically conserved β-tubulin gene confirmed two separate populations/species but also showed that the 'heterozygote' worms had a T. suis-like β-tubulin gene. A PCR-RFLP on the ITS-2 region was developed, that could distinguish between worms of the pig, human and 'heterozygote' type. The data suggest that Trichuris in pigs and humans belong to two different populations (i.e. are two different species). However, the data presented also suggest that cross-infections of humans with T. suis takes place. Further studies on sympatric Trichuris populations are highly warranted in order to explore transmission dynamics and unravel the zoonotic potential of T. suis.

Water from wastewater-polluted streams and dug-outs is the most commonly used water source for irrigation in urban farming in Ghana, but helminth parasite eggs in the water represent health risks when used for crop production. Conventional water treatment is expensive, requires advanced technology and often breaks down in less developed countries so low cost interventions are needed. Field and laboratory based trials were carried out in order to investigate the effect of the natural coagulant Moringa oleifera (MO) seed extracts in reducing helminh eggs and turbidity in irrigation water, turbid water, wastewater and tap water. In medium to high turbid water MO extracts were effective in reducing the number of helminth eggs by 94–99.5% to 1–2 eggs per litre and the turbidity to 7–11 NTU which is an 85–96% reduction. MO is readily available in many tropical countries and can be used by farmers to treat high turbid water for irrigation, however, additional improvements of water quality, e.g. by sand filtration, is suggested to meet the guideline value of ≤1 helminth egg per litre and a turbidity of ≤2 NTU as recommended by the World Health Organization and the U.S. Environmental Protection Agency for water intended for irrigation. A positive correlation was established between reduction in turbidity and helminth eggs in irrigation water, turbid water and wastewater treated with MO. This indicates that helminth eggs attach to suspended particles and/or flocs facilitated by MO in the water, and that turbidity and helminth eggs are reduced with the settling flocs. However, more experiments with water samples containing naturally occurring helminth eggs are needed to establish whether turbidity can be used as a proxy for helminth eggs.

Integrated chemotherapy of neglected tropical diseases (NTD) through mass drug administration given as a single dose would increase treatment coverage and cost-effectiveness. This study reports on the safety of a combination of albendazole, ivermectin and praziquantel in the treatment of lymphatic filariasis (LF), schistosomiasis and soil-transmitted helminthiasis (STH) in infected children. In this randomised, controlled, single-blinded clinical trial conducted in 235 primary school children aged 5-18 years in Yumbe District in Northern Uganda, the triple combination therapy was compared with the current NTD programme regimen. Liver function testing was performed for all children who received combined therapy. The study included 48 children with LF alone, 60 children with schistosomiasis (Schistosoma mansoni), 41 children with STH, 49 children with schistosomiasis + LF and 37 children with all three types of infection. Children were closely monitored by a paediatrician for any adverse reactions for 7 days. No serious adverse events were experienced. However, 4 of 18 children in the test group and 2 of 3 children in the control group who did not report any ill conditions before treatment developed adverse drug reactions. The combined and conventional therapies were found to be equally safe. The efficacies of both therapies were comparable and satisfactory. [ClinicalTrials.gov identifier: NCT01050517].

SUMMARYObjective. There is limited information on the acceptability and safety of praziquantel for treatment of schistosomiasis in children below the age of four years. In addition, although mebendazole has been extensively used together with praziquantel against infections with schistosomiasis and soil-transmitted helminthiasis (STH) in school-aged children, no specific acceptability or safety studies have been published on this drug combination in younger children. Methods. A randomized clinical trial was conducted to determine the safety of praziquantel alone and in combination with mebendazole in the treatment of Schistosoma mansoni and STH in children aged 1 to 4 years. Results. A total of 596 children from Bwondha fishing community in Mayuge district and Wang-Kado fishing community in Nebbi district were investigated using duplicate Kato-Katz thick smears of two stool samples and 130 (21·8%) were found infected with S. mansoni. Of these, 19·2% (25) had heavy intensity of infections. Of the infected children, 82 were included and randomised into praziquantel (40 mg/kg) + mebendazole (500 mg) or praziquantel (40 mg/kg) alone. Conclusion. Many symptoms were reported before treatment while very few were reported after treatment and all on treatment day. No serious adverse events were reported or observed after treatment. Praziquantel with or without mebendazole was well tolerated in small children in the study area.

Prevalence, incidence and seasonal variation of Cryptosporidium and Giardia duodenalis were studied over a 12-month period in 100 children from four pre-schools in Kafue, Zambia. Questionnaire data and a single stool sample were collected monthly from each child. Samples were processed using a commercial kit (Meridian Diagnostics Inc., USA) and oo(cysts) visualised by immunofluorescence microscopy. Cryptosporidium was detected in 30.7% (241/786; 95% CI = 27.5-33.9) while G. duodenalis was detected in 29.0% (228/786; 95% CI = 25.8-32.2). A total of 86% experienced one or more episodes of cryptosporidiosis while 75% had giardiasis. Cumulative incidence per 100 children was 75.4 for Cryptosporidium and 49.0 for G. duodenalis. Both infections were significantly more common in the wet compared to the dry season (34.8%, 162/466 vs. 24.7%, 79/320, P = 0.003 and 35.2%, 164/466 vs. 20.0%, 64/320, P < 0.001, respectively). Thus, risk ratios (RR) were 1.41 (95% CI = 1.13-1.77) and 1.76 (95% CI = 1.38-2.27) for Cryptosporidium and Giardia, respectively. Diarrhoea was significantly associated with cryptosporidiosis (RR = 1.23, 95% CI = 1.03-1.47; P = 0.029) but not with giardiasis (RR = 1.12, 95% CI = 0.91-1.53; P = 0.26). We conclude that gastro-intestinal protozoal infections are highly prevalent among children attending pre-school in peri-urban Zambia highlighting the need for further studies of risk factors.

Intestinal parasitic infections are among the most widespread of human infections in developing countries, and children are the most vulnerable. The aim of this study was to determine the prevalence of the protozoa Cryptosporidium and Giardia, as well as prevalence and intensity of intestinal helminths in children attending pre-school or day-care centres in Kafue District, Zambia. Single stool samples were collected from 403 children from 10 pre-schools and were subjected to duplicate Kato-Katz thick smears to identify and quantify helminths. A commercial immunofluorescence kit was used to identify Cryptosporidium- and Giardia-positive samples. The overall prevalence of helminth infection was 17.9%. Ascarislumbricoides was found in 12.0%, hookworm in 8.3%, Taenia spp. in 0.9%, Hymenolepisnana in 0.6% and Schistosomamansoni in 0.3%. The overall prevalence of Cryptosporidium and Giardia was 28.0 and 29.0%, respectively, with more girls infected with Giardia (33.8%) than boys (22.7%) (P=0.02). Significant differences in infections with A. lumbricoides and Cryptosporidium were observed between the various pre-schools (P < 0.001). These findings indicate that intestinal parasites are prevalent in children enrolled in pre-schools in Zambia. Future studies should explore local factors associated with transmission of these infections, and consequently provide the necessary health education to parents and teachers.

Medicinal plants are used worldwide in primary health care and also for modern drug discovery programs. More than 13,000 species of Medicinal and Aromatic Plants are used in traditional medicines and herbal cosmetics throughout the world and about 8000 of these are used in South Asia alone. In Bhutan, while the total number of species used by Local Healing System(s) is unknown, more than 500 species of medicinal plants are recorded in the pharmacopoeia of Bhutanese traditional medicine called g.so-ba-rig-pa (Sowa Rigpa). Currently 300 species, which grow in diverse ecological zones of the country, are used by the Institute of Traditional Medicine Services in formulating 98 different essential Sowa Rigpa medicines. In 2007, 16 tons of medicinal plants were procured by the institute alone and 85% of them, almost all wild species, were collected within the country. Unless properly managed, the sustainability of these wild medicinal plants is likely to be threatened. In this light, our paper describes the possible risk factors that may affect the sustainable use of medicinal plants in Bhutan. Four broad risk factors, which include biological, ecological, social and economic issues, are identified here. Our paper also throws light to the current policies, frameworks and acts that are put in place to ensure the sustainable use of medicinal plants in Bhutan and finally suggests future directions.

Zoonotic parasites are a significant food safety problem, particularly in Asia. In Vietnam fishborne zoonotic trematodes (FZT) are highly prevalent in fish cultured in grow-out farms. However, FZT infection status of juveniles produced and distributed by hatcheries and nurseries is unknown. Here we report an epidemiological investigation on FZT in fry and juveniles of major cultured freshwater fish species in four provinces of the Mekong Delta of Vietnam. No FZT infections were found in 14 species of fry sampled from hatcheries. In contrast, nursery juveniles of river catfish, hybrid catfish, giant gouramy, climbing perch, common carp, kissing gouramy, silver barb, silver carp, grass carp, Indian carp, pacu, tilapia and snakeskin gouramy were frequently infected with FZT metacercariae (range 1.2–29.7%). Seasonal variation in prevalence was observed: prevalence in river catfish and hybrid catfish were maximal in January, at the end of the flooding season, while the prevalence in juveniles of giant gouramy, climbing perch, common carp, kissing gouramy, silver barb, silver carp grass carp, mrigal and pacu were higher in the wet season, June to November. Overall, FZT prevalence was highest in climbing perch and giant gouramy (29.7% and 27.8%, respectively) and the lowest in river catfish (1.2%). The density of FZT metacercariae in fish varied seasonally only in climbing perch which was maximal in the wet season (P