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Opisthorchiasis, caused by the foodborne trematode Opisthorchis viverrini, affects more than 8 million people in Southeast Asia. In the framework of a phase 2b clinical trial conducted in Lao People’s Democratic Republic, pharmacokinetic samples were obtained from 125 adult and adolescent O. viverrini-infected patients treated with 400 mg tribendimidine following the design of a sparse sampling scheme at 20 min and 2, 7.75, 8, and 30 h after treatment using dried blood spot sampling., Opisthorchiasis, caused by the foodborne trematode Opisthorchis viverrini, affects more than 8 million people in Southeast Asia. In the framework of a phase 2b clinical trial conducted in Lao People’s Democratic Republic, pharmacokinetic samples were obtained from 125 adult and adolescent O. viverrini-infected patients treated with 400 mg tribendimidine following the design of a sparse sampling scheme at 20 min and 2, 7.75, 8, and 30 h after treatment using dried blood spot sampling. Pharmacokinetic data for the metabolites deacetylated amidantel (dADT) and acetylated dADT (adADT) were pooled with data from two previous ascending-dose trials and evaluated using nonlinear mixed-effects modeling. The observed pharmacokinetic data were described using a flexible transit absorption model for the active metabolite dADT, followed by one-compartment disposition models for both metabolites. Significant covariates were age, body weight, formulation, and breaking of the enteric coating on the tablets. There were significant associations between O. viverrini cure and both the dADT maximum concentration and the area under the concentration-time curve (P < 0.001), with younger age being associated with a higher probability of cure. Modeling and simulation of exposures in patients with different weight and age combinations showed that an oral single dose of 400 mg tribendimidine attained therapeutic success in over 90% of adult patients. Our data confirmed that tribendimidine could be a valuable novel alternative to the standard treatment, praziquantel, for the treatment of O. viverrini infections.

The tegumental changes in adult Opisthorchis viverrini induced by tribendimidine were analyzed by scanning electron microscopy (SEM). We exposed O. viverrini to tribendimidine at a concentration of 10 microg/ml for 4 h. In addition, hamsters were treated with a single 400 mg/kg oral dose of tribendimidine and flukes were recovered from the bile ducts 24, 48, 72, and 96 h post-treatment. SEM analysis of the flukes incubated in vitro showed only mild damage of the tegument. Twenty-four hours post-treatment of hamsters, extensive disruption such as sloughing, furrowing, or blebbing of the tegument was evident, which did not increase in severity 48-72 h post-treatment. Ninety-six hours after tribendimidine administration, the majority of flukes had been expelled. A single 400 mg/kg oral dose of tribendimidine administered to O. viverrini-infected hamsters yielded a worm burden reduction of 63.0%. In conclusion, our experiments confirm that tribendimidine possesses interesting trematocidal properties, which warrant additional investigations and provide further data for subsequent clinical trials.

Background Low- and middle-income countries are facing a dual disease burden with infectious diseases (e.g., gastrointestinal tract infections) and non-communicable diseases (e.g., diabetes) being common. For instance, chronic parasite infections lead to altered immune regulatory networks, anemia, malnutrition, and diarrhea with an associated shift in the gut microbiome. These can all be pathways of potential relevance for insulin resistance and diabetes. The aim of this study was to investigate the association between common gastrointestinal tract infections and glycemia in children from non-fee paying schools in South Africa. Methodology We conducted a cross-sectional survey among 9- to 14-year-old school children in Port Elizabeth. Stool and urine samples were collected to assess infection status with parasitic worms (e.g., Ascaris lumbricoides, Enterobius vermicularis, and Trichuris trichiura), intestinal protozoa (e.g., Cryptosporidium parvum and Giardia intestinalis), and the bacterium Helicobacter pylori. Glycated hemoglobin (HbA1c) was measured in finger prick derived capillary blood. All children at schools with a high prevalence of helminth infections and only infected children at the schools with low infection rates were treated with albendazole. The association of anthelmintic treatment with changes in HbA1c 6 months after the drug intervention was also investigated. Findings A high prevalence of 71.8% of prediabetes was measured in this group of children, with only 27.8% having HbA1c in the normal range. H. pylori was the predominant infectious agent and showed an independent positive association with HbA1c in a multivariable regression analysis (β = 0.040, 95% confidence interval (CI) 0.006–0.073, p, Author summary Parasitic worms (e.g., pinworm, roundworm, and whipworm), intestinal protozoa (e.g., Cryptosporidium parvum and Giardia intestinalis), and the bacterium Helicobacter pylori persist at high rates in the gastrointestinal tract of people from low- and middle-income countries. These infectious agents are increasingly paralleled by high rates of non-communicable diseases, such as diabetes. We studied the association of glycemia, measured as HbA1c with common gastrointestinal tract infections among school children aged 9–14 years from disadvantaged neighborhoods in Port Elizabeth, South Africa. Our goal was to deepen the understanding of whether specific gastrointestinal tract infections might be early life determinants of elevated HbA1c levels that might lead to diabetes. We found that the bacterium H. pylori was very common among our group of children with a positive association with hyperglycemia. None of the other infectious agents showed such an association. Additional, longitudinal studies are needed to determine whether there is causality for the observed association between H. pylori and hyperglycemia. The integration of biomarkers will allow studying mediating mechanisms.

Background Endemicity of lymphatic filariasis (LF) in Cambodia was proven in 1956 when microfilariae were detected in mosquitos in the Kratié province. In 2001, an extensive study confirmed the presence of both Brugia malayi and Wuchereria bancrofti microfilariae. In 2003, the Ministry of Health established a national task force to develop policies and strategies for controlling and eliminating neglected tropical diseases (NTDs), with the goal of eliminating LF by 2015. This article summarizes the work accomplished to eliminate LF as a public health problem in Cambodia. Methods The National Program to Eliminate Lymphatic Filariasis made excellent progress in the goal towards elimination due to strong collaboration between ministries, intensive supervision by national staff, and advocacy for mobilization of internal and external resources. Mass drug administration (MDA) with diethylcarbamazine citrate and albendazole was conducted in six implementation units, achieving > 70% epidemiological coverage for five consecutive rounds, from 2005 to 2009. In 2006, in 14 provinces, healthcare workers developed a line list of lymphedema and hydrocele patients, many of whom were > 40 years old and had been affected by LF for many years. The national program also trained healthcare workers and provincial and district staff in morbidity management and disability prevention, and designated health centers to provide care for lymphedema and acute attack. Two reference hospitals were designated to administer hydrocele surgery. Results Effectiveness of MDA was proven with transmission assessment surveys. These found that less than 1% of school children had antigenemia in 2010, which fell to 0% in both 2013 and 2015. A separate survey in one province in 2015 using Brugia Rapid tests to test for LF antibody found one child positive among 1677 children. The list of chronic LF patients was most recently updated and confirmed in 2011–2012, with 32 lymphoedema patients and 17 hydrocele patients listed. All lymphedema patients had been trained on self-management and all hydrocele patients had been offered free surgery. Conclusions Due to the success of the MDA and the development of health center capacity for patient care, along with benefits gained from socioeconomic improvements and other interventions against vector-borne diseases and NTDs, Cambodia was validated by the World Health Organization as achieving LF elimination as a public health problem in 2016. Electronic supplementary material The online version of this article (10.1186/s40249-018-0394-7) contains supplementary material, which is available to authorized users.

We develop and analyse two population-based models of the transmission dynamics of the worm parasite Opisthorchis viverrini. The life cycle of O. viverrini includes humans, cats and dogs as definitive hosts; and snails and fish as intermediate hosts. The first model has only one definitive host (humans) while the second model has two additional hosts: the reservoir hosts, cats and dogs. We define reproduction numbers and endemic equilibrium points for the two models. We use prevalence data for the five hosts from two islands in Lao People’s Democratic Republic to estimate distributions of parameter values. We use these distributions to compute the sensitivity index and the partial rank correlation coefficient of the basic reproduction number and the endemic equilibrium point to the parameters. We calculate distributions of the host-specific type-reproduction number to show that humans are necessary to maintain transmission and can sustain transmission without additional reservoir hosts. Therefore interventions targeting humans could be sufficient to interrupt transmission of O. viverrini.

Background Infections with soil-transmitted helminths and pathogenic intestinal protozoa pose a considerable public health burden, particularly in low- and middle-income countries, including Nepal. We assessed the extent of intestinal parasite infections among schoolchildren in two districts of Nepal and determined underlying risk factors. Methods A cross-sectional survey was conducted between March and May 2015 in the districts of Dolakha and Ramechhap, Nepal. A total of 708 children, aged 8–16 years from 16 purposively selected schools, were enrolled. Each child provided a single stool sample that was subjected to a suite of copro-microscopic diagnoses for intestinal protozoa and helminths. Drinking water samples from different sources at schools (n = 29), community places (n = 43) and households (n = 562) were analysed for contamination with thermotolerant coliforms (TTC). A questionnaire was administered to determine individual- and household-level risk factors of intestinal parasite infections. Self-reported symptoms were assessed and a clinical examination was undertaken by a physician. Haemoglobin was measured and used as a proxy for anaemia. Mixed logistic regression models were applied to investigate associations. Results The overall prevalence of intestinal parasite infections was 39.7%. Trichuris trichiura (30.9%), Giardia intestinalis (30.5%) and hookworm (30.2%) were the predominant intestinal parasite infections. Children from households lacking soap for handwashing were at higher odds of intestinal parasite infections than children who had soap [adjusted odds ratio (aOR) 1.81; 95% confidence interval (CI): 1.13–2.89; P = 0.01]. Children from households without freely roaming domestic animals showed lower odds of G. intestinalis compared to children from households with freely roaming animals (aOR 0.52; 95% CI: 0.33–0.83; P = 0.01). One out of three (31.0%) children suffered from fever and 22.4% had watery diarrhoea within a two-week recall period. Anaemia was diagnosed in 23.6% of the children. Water contamination with TTC showed no clear association with intestinal parasite infection. Conclusions Intestinal parasites are common among schoolchildren in the two surveyed districts of Nepal. An important risk factor was lack of soap for handwashing. Our findings call for efforts to control intestinal parasite infection and emphasis should be placed on improvements in water, sanitation and hygiene interventions. Trial registration ISRCTN17968589 (date assigned: 17 July 2015). Electronic supplementary material The online version of this article (10.1186/s13071-018-3105-0) contains supplementary material, which is available to authorized users.

Background As a result of epidemiological transition, the health systems of low- and middle-income countries are increasingly faced with a dual disease burden of infectious diseases and emerging non-communicable diseases. Little is known about the mutual influence of these two disease groups. The aim of this study was to investigate the co-occurrence of helminth infections and diabetes mellitus in adults in Lao People’s Democratic Republic (Lao PDR). Methods We conducted a cross-sectional study among 1600 randomly selected adults aged 35 and older from four different socio-economical and ecological provinces. Information on socio-demographics, risk factors and health conditions was obtained from personal interviews. Clinical assessments including anthropometry (height, weight, waist and hip circumference) and blood pressure measurements were also conducted. Diabetes was classified based on self-reported diagnoses and a point-of-care glycated haemoglobin (HbA1c) test from finger prick blood samples. Stool samples for helminth diagnosis were examined with formalin-ether concentration technique for intestinal parasitic infections. The independent associations of helminth infections with diabetic status and HbA1c were assessed using multiple regression analyses. Results The prevalence of pre-diabetes and diabetes was 37.3% and 22.8%, respectively. Fifty-six percent of diabetic cases were undiagnosed and 85% of diagnosed diabetic cases had poor glycemic control. Participants from rural areas and from southern parts of the country had higher infection rates, with Opisthorchis viverrini, being the most common helminth infection (30.5%). We found a positive association between Taenia spp. infections and HbA1c (β = 0.117; 95% CI: 0.042–0.200) and diabetes mellitus risk (OR = 2.98; 95% CI: 1.10–8.05). No other helminth species was associated with glycated hemoglobin. Conclusions Hyperglycaemia and diabetic rates in Lao PDR are alarmingly high, but consistent with other high rates in the region. Given the high rates of under-diagnosis and poorly-controlled glycaemia in diabetes mellitus patients, routine diabetes screening and treatment is essential for the local healthcare system. Large longitudinal cohorts integrating biomarkers are warranted in the search of causal diabetes mellitus risk factors in the region. Common intestinal helminth infections, including O. viverrini, are unlikely to explain the high diabetes mellitus rates observed. Electronic supplementary material The online version of this article (10.1186/s40249-018-0488-2) contains supplementary material, which is available to authorized users.

Background Strongyloides stercoralis and hookworm are two soil-transmitted helminths (STH) that are highly prevalent in Cambodia. Strongyloides stercoralis causes long-lasting infections and significant morbidity but is largely neglected, while hookworm causes the highest public health burden among STH. The two parasites have the same infection route, i.e. skin penetration. The extent of co-distribution, which could result in potential high co-morbidities, is unknown in highly endemic settings like Cambodia. The aim of this study was to predict the spatial distribution of S. stercoralis-hookworm co-infection risk and to investigate determinants of co-infection in Preah Vihear Province, North Cambodia. Methods A cross-sectional survey was conducted in 2010 in 60 villages of Preah Vihear Province. Diagnosis was performed on two stool samples, using combined Baermann technique and Koga agar culture plate for S. stercoralis and Kato-Katz technique for hookworm. Bayesian multinomial geostatistical models were used to assess demographic, socioeconomic, and behavioural determinants of S. stercoralis-hookworm co-infection and to predict co-infection risk at non-surveyed locations. Results Of the 2576 participants included in the study, 48.6% and 49.0% were infected with S. stercoralis and hookworm, respectively; 43.8% of the cases were co-infections. Females, preschool aged children, adults aged 19–49 years, and participants who reported regularly defecating in toilets, systematically boiling drinking water and having been treated with anthelmintic drugs had lower odds of co-infection. While S. stercoralis infection risk did not appear to be spatially structured, hookworm mono-infection and co-infection exhibited spatial correlation at about 20 km. Co-infection risk was positively associated with longer walking distances to a health centre and exhibited a small clustering tendency. The association was only partly explained by climatic variables, suggesting a role for underlying factors, such as living conditions and remoteness. Conclusions Both parasites were ubiquitous in the province, with co-infections accounting for almost half of all cases. The high prevalence of S. stercoralis calls for control measures. Despite several years of school-based de-worming programmes, hookworm infection levels remain high. Mebendazole efficacy, as well as coverage of and compliance to STH control programmes should be investigated. Electronic supplementary material The online version of this article (10.1186/s13071-017-2604-8) contains supplementary material, which is available to authorized users.

The occurrence and spatial distribution of intestinal helminth infection in children is fairly well understood. However, knowledge on how helminth infections govern intestinal morbidity is scarce. We conducted a cross-sectional study to assess and quantify the relationship between single and multiple species helminth infection with clinical and self-reported morbidity indicators and nutritional status in Champasack province, southern Lao People's Democratic Republic (Lao PDR). A random sample of 1313 children, aged 6 months to 12 years, from villages in nine rural districts were enrolled and examined for helminth infection using duplicate Kato-Katz thick smears. Morbidity was assessed by self-reported symptoms, coupled with clinical examination and appraisal of nutritional status and anaemia. Bivariate and multivariate logistic regression was employed to study associations between helminth infection and morbidity indicators and anaemia. We found considerable morbidity among the surveyed children, including hepatomegaly (13.7%), pale conjunctiva (13.2%) and abdominal pain (10.4%). Anaemia was recorded in 60.4% of the children, whilst signs of stunting and low body mass index (BMI) were observed in 49.8% and 33.3% of the surveyed children, respectively. Hookworm and Opisthorchis viverrini were the predominant helminth species with prevalences of 51.0% and 43.3%, respectively. The prevalence of Schistosoma mekongi in the surveyed children was 5.6%. Multiple species helminth infections were recorded in 40.4% of the study cohort. Morbidity was associated with specific helminth species infection (e.g. S. mekongi with hepatomegaly; adjusted odds ratio (aOR): 9.49, 95% confidence interval (CI): 2.07-43.51) and multiparasitism (e.g. two or more helminth species with abdominal pain; aOR: 2.40, 95% CI: 1.46-3.93). Anaemia was associated with hookworm infection (aOR: 1.64, 95% CI: 1.16-2.34) and multiparasitism (aOR: 1.64, 95% CI: 1.18-2.29). Low BMI was associated with O. viverrini infection (aOR: 1.68, 95% CI: 1.14-2.49) and multiparasitism (aOR: 1.42, 95% CI: 1.01-2.00). The multiple strong associations reported here between helminth infections (single or multiple species) and intestinal morbidity among children in rural parts of southern Lao PDR call for concerted efforts to control helminth infections, which in turn might improve children's health and development.

Northern Cambodia and Southern Laos are highly endemic for Schistosoma mekongi. However, there is currently no immunological assay available that is specific for this form of schistosomiasis. We have validated Schistosoma mansoni antigens to detect S. mekongi-directed antibodies in human sera collected from a highly S. mekongi endemic region in Laos. On two consecutive days stool samples of 234 individuals were analyzed by Kato-Katz for presence of S. mekongi eggs and the results were correlated with serology. A sensitivity of 94.5% was calculated for a combination of ELISA and indirect fluorescence assay (IFA) as compared to the detection of S. mekongi eggs in stool samples as gold standard. The results demonstrate that S. mansoni antigens can be used for the diagnosis of S. mekongi infections.

Background The prevalence of epilepsy is 7.7‰ in Laos and 5.8‰ in Cambodia, and the treatment gap exceeds 90% in both countries. Objective Our research program aims to measure the effectiveness of two community-based health care approaches using two different types of Domestic Health Visitors (DHV) trained to screen and follow patients with epilepsy (PWE): (1) in Laos, DHV were chosen from health center staff (2) in Cambodia, DHV were health volunteers residing in the villages. Patients and Methods / Material and Methods Between 2015 and 2017, these two quasi-experimental studies were conducted in rural districts over a 12- months period comparing an intervention area and a control area. Our intervention included an Information, Education and Communication campaign, specific training of the DHV staff, and regular monitoring. In Laos, the treatment gap was reduced by 5.5% (20 to 43 cases under treatment of the 418 expected) in the intervention area versus 0.5% (21 to 25 cases under treatment of the 788 expected) in the control area (p

In this study we reviewed Russian scientific literature (scientific publications, book chapters, monographs) published between 1 January 1979 and 31 August 2015 from two sources: Main database of the Russian Scientific Electronic Library (eLIBRARY, http://elibrary.ru/), and the Scientific Medical Library of Siberian State Medical University (http://medlib.tomsk.ru/). Specifically, the review details the infection prevalence of Opisthorchis felineus (O. felineus) in Western Siberia, Russian Federation. From the primary key words screening, 1591 records were identified from which 32 Russian-language publications were relevant. The lowest O. felineus infection rate of 0.4% was reported in Tatarstan Republic, and the highest reached 83.9% in the Khanty-Mansiysk Autonomous Okrug. The infection prevalence was lower in children than in adults and increased with age. O. felineus infection was detected more often in indigenous population than in migrants. Infection intensity in western regions (Permskaya, Bryanskaya Oblast) was low and varied from 15 to 336 eggs per gram stool (epg), while in endemic regions it reached more than 2000 epg. In some settlements the mean intensity infection was 5234 epg. The high rates of intensity were registered in regions with a high prevalence of infection. Based on obtained data, a map of O. felineus infection prevalence in Western Siberia was developed. After mapping the results, the highest prevalence was detected in Tyumenskaya Oblast with over 60%, while the Tomskaya Oblast had the lowest prevalence at fewer than 19.0%. Khanty-Mansiysk Autonomus Okrug, Altaiskii Krai, Novosibirskaya Oblast and Omskaya Oblast had an average level of O. felineus infection of 20-39%. According to the results of the review, Western Siberia must be considered as highly endemic region for opisthorchiasis in the Russian Federation. The development of a control program specific for the Russian community is warranted.

Praziquantel is the only option for treatment of the liver fluke infection Opisthorchis viverrini. Tribendimidine could be an alternative drug. We aimed to assess the efficacy and safety of a single, oral dose of tribendimidine, compared with praziquantel administered in two doses, in participants with O viverrini infection.We did an open-label, randomised, non-inferiority, phase 2 trial in children (8-14 years) and adolescents and adults (≥15 years) in Champasack province, southern Laos. Participants infected with O viverrini were randomly assigned (1:1), via a computer-generated block-randomisation procedure (block sizes of two, four, and six), to receive a single, oral dose of tribendimidine (200 mg for children, 400 mg for adolescents and adults) or two oral doses of praziquantel (50 mg/kg bodyweight and 25 mg/kg bodyweight, 6 h apart). Physicians assessing adverse events and laboratory personnel were masked to treatment allocation, but the investigators administering treatment and the participants could have recognised the treatment group based on differences in the number, appearance, and odour of the tablets. The primary outcomes were cure rate, defined as no parasite eggs in stool at 3 weeks' follow-up, and egg reduction rate. We did available-case analysis of all participants with primary endpoint data. The non-inferiority margin for the difference in cure rates between the groups was pre-specified as -3 percentage points. Adverse events were monitored at 3 h and 24 h after treatment. This trial is registered, number ISRCTN96948551.Between Feb 1, and April 30, 2014, we assigned 607 participants with confirmed O viverrini infection to receive tribendimidine (n=300) or praziquantel (n=307). 11 participants (five in the tribendimidine group and six in the praziquantel group) did not provide stool samples at 3 weeks' follow-up and were excluded from the available-case analysis. 276 (93·6%) of 295 participants in the tribendimidine group were cured compared with 293 (97·3%) of 301 participants in the praziquantel group. The difference in cure rates between the two groups was -3·8 percentage points (95% CI -7·1 to -0·4), thus the lower limit of the confidence interval exceeded the non-inferiority margin. In both treatment groups, egg reduction rates were 99·9%. Adverse events were of mild and moderate intensity and were more frequent in the praziquantel group than in the tribendimidine group (odds ratio 4·5, 95% CI 3·2-6·3; p0·0001). The most frequent adverse events were headache, vertigo, nausea, and fatigue.Tribendimidine has a slightly lower cure rate than praziquantel and non-inferiority was not shown. However, tribendimidine has a similar egg reduction rate to praziquantel and leads to fewer adverse events and thus might complement praziquantel in O viverrini control programmes, particularly in settings co-endemic for hookworm.Joint Global Health Trials scheme from the Wellcome Trust, Department for International Development, and Medical Research Council.

Summary Objectives The epilepsy treatment gap is large in low‐ and middle‐income countries, but the reasons behind nonadherence to treatment with antiepileptic drugs (AEDs) across African countries remain unclear. We investigated the extent to which AEDs are not taken and associated factors in people with active convulsive epilepsy (ACE) identified in cross‐sectional studies conducted in five African countries. Methods We approached 2,192 people with a confirmed diagnosis of ACE for consent to give blood voluntarily. Participants were asked if they were taking AEDs, and plasma drug concentrations were measured using a fluorescence polarization immunoassay analyzer. Information about possible risk factors was collected using questionnaire‐based clinical interviews. We determined factors associated with nonadherence to AED treatment in children and adults, as measured by detectable and optimal levels, using multilevel logistic regression. Results In 1,303 samples assayed (43.7% were children), AEDs were detected in 482, but only 287 had optimal levels. Of the 1,303 samples, 532 (40.8%) were from people who had reported they were on AEDs. The overall prevalence of nonadherence to treatment was 63.1% (95% confidence interval [CI] 60.5–65.6%) as measured by detectable AED levels and 79.1% (95% CI 73.3–84.3%) as measured by optimal AED levels; self‐reported nonadherence was 65.1% (95% CI 45.0–79.5%). Nonadherence was significantly (p

International audience; IntroductionAlors que les prévalences en Asie du sud-est (7,7‰ au Laos et 5,8‰ au Cambodge) sont proches de celle observée en France (6‰), l’enjeu de santé publique pour ces pays relève avant tout du déficit thérapeutique qui est supérieur à 95 % au Laos comme au Cambodge. L’objectif principal de notre programme de recherche était de mesurer l’efficience d’une nouvelle approche des soins de santé de proximité en testant deux stratégies : (1) des visites villageoises mensuelles des personnels des centres de santé (nommés DHV) formés au dépistage et au suivi des patients épileptiques au Laos vs (2) une stratégie identique où les missions du DHV étaient assurées par les volontaires de santé résidant dans les villages au Cambodge.MéthodeCes deux études quasi-expérimentales d’une durée de 12 mois (réalisées en 2015–2016 au Laos et en 2016–2017 au Cambodge) ont été conduites dans des districts ruraux grâce à une approche comparée entre une zone d’intervention et une zone contrôle. Notre recherche a ainsi permis des analyses comparatives « avant–après et ici–ailleurs » pour démontrer l’efficacité de l’intervention dans chaque pays, ainsi qu’une comparaison entre les deux stratégies d’intervention.RésultatsAu Laos, après 12 mois d’expérimentation, le déficit de traitement a baissé de 5,5 % dans la zone d’intervention contre 0,5 % dans la zone contrôle (p = 0,0001). Dans la zone d’intervention, 36,1 % des épileptiques ont refusé le traitement, 27,8 % ont préféré être soigné sans passer par le centre de santé primaire (circuit de proximité) ; et parmi ceux qui ont adhéré, le suivi à domicile a permis d’augmenter de 27,6 % le nombre de compliants (p = 0,019). Au Cambodge, après 6 mois d’expérimentation, la stratégie a permis de baisser significativement le déficit de traitement de 31,1 % dans la zone d’intervention, au regard des 7,0 % de baisse dans la zone contrôle (p = 0,0001). Incontestablement, la stratégie est plus efficace lorsque le DHV réside dans le village.ConclusionD’ores et déjà, les points positifs de l’expérimentation au Laos ont permis la rédaction d’une « Advocacy Policy » (promotion et politique) favorablement accueillis par le Ministère de la Santé au Laos, comme cela est également envisagé au Cambodge à la fin de notre intervention en juin 2017.

Background Multiple factors determine children’s nutritional status, including energy and nutrient intake, recurrent infectious diseases, access (or lack thereof) to clean water and improved sanitation, and hygiene practices, among others. The “Vegetables go to School: improving nutrition through agricultural diversification” (VgtS) project implements an integrated school garden programme in five countries, including Burkina Faso. The aim of this study was to determine the prevalence of undernutrition and its risk factors among schoolchildren in Burkina Faso before the start of the project. Methods In February 2015, a cross-sectional survey was carried out among 455 randomly selected children, aged 8–14 years, in eight schools in the Plateau Central and Centre-Ouest regions of Burkina Faso. Nutritional status was determined by anthropometric assessment. Helminth and intestinal protozoa infections were assessed using the Kato-Katz and a formalin-ether concentration method. A urine filtration technique was used to identify Schistosoma haematobium eggs. Prevalence of anaemia was determined by measuring haemoglobin levels in finger-prick blood samples. Questionnaires were administered to children to determine their knowledge of nutrition and health and their related attitudes and practices (KAP). Questionnaires were also administered to the children’s caregivers to identify basic household socio-demographic and economic characteristics, and water, sanitation and hygiene (WASH) conditions. To determine the factors associated with schoolchildren’s nutritional status, mixed logistic regression models were used. Differences and associations were considered statistically significant if P-values were below 0.05. Results Complete datasets were available for 385 children. The prevalence of undernutrition, stunting and thinness were 35.1%, 29.4% and 11.2%, respectively. The multivariable analysis revealed that undernutrition was associated with older age (i.e. 12–14 years compared to

Objectives To determine the magnitude, risk factors and causes of premature mortality associated with epilepsy in low and middle income countries (LMIC). Methods We conducted a systematic search of the literature reporting mortality and epilepsy in the World Bank-defined LMIC. We assessed the quality of the studies based upon representativeness, ascertainment of cases, diagnosis, and mortality, and extracted data on standardized mortality ratios (SMR) and mortality rates in people with epilepsy. We examined risk factors and causes of death. Results The annual mortality rate was estimated at 19.8 (range 9.7-45.1) deaths per 1000 people with epilepsy with a weighted median SMR of 2.6 (range 1.3-7.2) among higher-quality population-based studies. Clinical cohort studies yielded 7.1 (range 1.6-25.1) deaths per 1000 people. The weighted median SMRs were 5.0 in males and 4.5 in females; relatively higher SMRs within studies were measured among children and adolescents, those with symptomatic epilepsies, and those reporting less adherence to treatment. The main causes of death in people with epilepsy living in LMICs include those directly attributable to epilepsy, which yield a mean proportional mortality ratio (PMR) of 27.3% (range 5%-75.5%) derived from population-based studies. These direct causes comprise status epilepticus, with reported PMRs ranging from 5%-56.6%, and sudden unexpected death in epilepsy, with reported PMRs ranging from 1%-18.9%. Important causes of mortality indirectly related to epilepsy include drowning, head injury, and burns. Significance Epilepsy in LMIC has a significantly greater premature mortality, as in high-income countries, but in LMIC the excess mortality is more likely to be associated with causes attributable to lack of access to medical facilities such as status epilepticus, and preventable causes such as drowning, head injuries and burns. This excess premature mortality could be substantially reduced with education about the risk of death and improved access to treatments, including AEDs.

This study assessed drinking water quality, sanitation, and hygiene (WASH) conditions among 708 schoolchildren and 562 households in Dolakha and Ramechhap districts of Nepal. Cross-sectional surveys were carried out in March and June 2015. A Delagua water quality testing kit was employed on 634 water samples obtained from 16 purposively selected schools, 40 community water sources, and 562 households to examine water quality. A flame atomic absorption spectrophotometer was used to test lead and arsenic content of the same samples. Additionally, a questionnaire survey was conducted to obtain WASH predictors. A total of 75% of school drinking water source samples and 76.9% point-of-use samples (water bottles) at schools, 39.5% water source samples in the community, and 27.4% point-of-use samples at household levels were contaminated with thermo-tolerant coliforms. The values of water samples for pH (6.8–7.6), free and total residual chlorine (0.1–0.5 mg/L), mean lead concentration (0.01 mg/L), and mean arsenic concentration (0.05 mg/L) were within national drinking water quality standards. The presence of domestic animals roaming inside schoolchildren’s homes was significantly associated with drinking water contamination (adjusted odds ratio: 1.64; 95% confidence interval: 1.08–2.50; p = 0.02). Our findings call for an improvement of WASH conditions at the unit of school, households, and communities.

Background The liver fluke Opisthorchis viverrini, highly prevalent in Southeast Asia, is an important public health burden, including a risk factor for developing an aggressive bile duct cancer, cholangiocarcinoma, in chronically infected patients. Praziquantel, administered at a single 40 mg/kg dose in preventive chemotherapy programs and 3 × 25 mg/kg for individual treatment, is the drug of choice, yet information on the nature of the dose-response relationship is lacking. Methods We performed a randomized, parallel, single-blind dose-ranging phase 2 trial in the Lao People’s Democratic Republic in O. viverrini–infected adults. Patients were randomly assigned to 30 mg/kg, 40 mg/kg, 50 mg/kg, or 3 × 25 mg/kg praziquantel or placebo. Adverse events were recorded at baseline, 3 hours, and 24 hours posttreatment. Cure rates (CRs) and egg reduction rates (ERRs) were estimated 3 weeks after drug administration using available case analysis. Dose-response curves were predicted using Emax models. Results Two-hundred seventeen O. viverrini–infected patients were assigned to the 5 treatment arms. The majority (94.3%) of patients harbored light infections. The Emax model predicted a high efficacy among the observed dose range. We observed CRs ranging from 92.7% to 95.5% and ERRs >99.5% for all praziquantel treatment groups. Adverse events were mild but higher in the standard treatment group (3 × 25 mg/kg) than in the single-dose treatment arms. Conclusions Single-dose praziquantel appears to be as efficacious as the standard 3 × 25 mg/kg regimen for the treatment of O. viverrini infections, while presenting fewer adverse events. Further studies are necessary in moderate and heavy O. viverrini infections. Clinical trials registration Randomized Controlled Trials (ISRCTN77186750).

Objective: Giardiasis, a zoonotic, diarrheal disease with worldwide occurrence, is routinely diagnosed by microscopic examination of stool samples. However, implementation of this method relies on skilled and experienced personal; it is time consuming and relatively low in sensitivity. A superior diagnostic approach to detect the causative agent Giardia intestinalis would, hence, be highly desirable. The current study aimed to assess realtime polymerase chain reaction (PCR) for the detection of G. intestinalis as an alternative to microscopy. Material and methods: Stool samples from healthy schoolchildren aged 8-14 years from eight schools of the Centre-Ouest and Plateau Central regions in Burkina Faso were therefore collected within a cross-sectional study. Microscopic examination was performed on two faecal samples collected over two consecutive days from 441 schoolchildren. Each faecal specimen has been examined using Kato-Katz and formol-ether methods of concentration in addition to the direct examination. Real-time PCR was used to detect G. intestinalis in the 94 microscopy positive and the 53 microscopy negative samples. Results: Microscopic examination demonstrated an overall G.intestinalis prevalence of 27.2%. Using the microscopic examination as the ‘gold standard’, the overall sensitivity of real-time PCR was demonstrated to be 76.6% ranging from 58.3% to 94.1% and the specificity was 96.2% ranging from 96.2% to 100% across the schools assessed. Conclusion: Real-time PCR appears to be a solid detection method for G. intestinalis in this current setting. However, it needs to be further optimized to become a more sensitive tool for G. intestinalis diagnosis in low income settings.

Little is known about the genetic variability of the soil-transmitted nematode, Strongyloides stercoralis, in humans. We sequenced portions of the small subunit rDNA (SSU), including the hyper variable regions (HVR) I and IV from S. stercoralis larvae derived from individuals living in a rural setting in Cambodia. We identified three polymorphic positions, including a previously reported one within the HVR I. HVR IV was invariable. Six different SSU alleles existed in our sample. Although different genotypes of S. stercoralis were found in the same individuals, no heterozygous larvae were found. This indicates that there is no or very little interbreeding between the different genotypes. Further studies are needed to examine if this is because sexual reproduction, which is facultative, is rare in our study area's S. stercoralis population or because what is considered to be S. stercoralis today is actually a complex of closely related species or subspecies.

SUMMARYThe variability of larval excretion impedes the parasitological diagnosis ofStrongyloides stercoralisin infected individuals. We assessed the number of larvae excreted per gram (LPG) stool in 219 samples from 38 infected individuals over 7 consecutive days before and in 470 samples from 44 persons for 21 consecutive days after ivermectin treatment (200 μg kg−1BW). The diagnostic sensitivity of a single stool sample was about 75% for individuals with low-intensity infections (⩽1 LPG) and increased to 95% for those with high-intensity infections (⩾10 LPG). Doubling the number of samples examined per person increased sensitivity to more than 95%, even for low-intensity infections. There was no indication of a cyclic excretion of larvae. After treatment, all individuals stopped excreting larvae within 3 days. Larvae were not detected during any of the following 18 days (total 388 Baermann and 388 Koga Agar tests). Two stool samples, collected on consecutive days, are recommended in settings where low or heterogeneous infection intensities are likely. In this way, taking into account the possible biological variability in excretion, the efficacy of ivermectin treatment can be assessed as soon as 4 days after treatment.

Preventative chemotherapy without community hygiene and animal health programs may be leading to emergence of this zoonosis., Ancylostoma ceylanicum, a hookworm of canids and felids in Asia, is becoming the second most common hookworm infecting humans. In 2012, we investigated the prevalence and infection dynamics of and risk factors for hookworm infections in humans and dogs in a rural Cambodian village. Over 57% of the population was infected with hookworms; of those, 52% harbored A. ceylanicum hookworms. The greatest intensities of A. ceylanicum eggs were in persons 21-30 years of age. Over 90% of dogs also harbored A. ceylanicum hookworms. Characterization of the cytochrome oxidase-1 gene divided isolates of A. ceylanicum hookworms into 2 groups, 1 containing isolates from humans only and the other a mix of isolates from humans and animals. We hypothesize that preventative chemotherapy in the absence of concurrent hygiene and animal health programs may be a factor leading to emergence of A. ceylanicum infections; thus, we advocate for a One Health approach to control this zoonosis.

Among Paragonimus species, P. paishuihoensis is one of the most mysterious and poorly understood species. Metacercariae are characterized by having a unique dendritically branched excretory bladder. However, the morphology of the adult worm remains unknown. To date, metacercariae of this species have been reported only in China and Thailand. In this study, we first found P. paishuihoensis metacercariae in freshwater crabs, Potamon lipkei, in Hinheub District, Vientiane, Lao PDR, with a prevalence of 77.7% and the average intensity of 10.3 (range 1-28) metacercariae per crab. The molecular data based on ITS2 and CO1 markers indicated that P. paishuihoensis from Laos and Thailand were almost completely identical and were close to members of the Paragonimus bangkokensis/Paragonimus harinasutai complex. Attempts to infect experimental animals (cats, dogs, and rats) with P. paishuihoensis were unsuccessful, suggesting that these animals might be unsuitable definitive hosts for the species. Further studies are necessary to elucidate the taxonomic status and life cycle of P. paishuihoensis.

School surveys provide a convenient platform to obtain large child cohorts from multiple communities and are widely used as a proxy to determine community prevalence of neglected tropical diseases. The purpose of this study was to compare trachoma prevalence between preschool- and school-aged children and children who attend and do not attend school.; We analysed data from community-based trachoma surveys conducted from 2008-2011 in Ethiopia, Mali, Niger and Nigeria. The surveys utilised a cross-sectional, randomised cluster design. Individual-level data on school attendance was collected.; Overall, 75 864 children aged 1-15 years from 2100 communities were included in the analysis. The prevalence of trachomatous inflammation follicular (TF) among these children in surveyed districts was 19.1% (95% CI 17.9-20.2%) in Ethiopia, 6.2% (95% CI 5.4-6.9%) in Niger, 4.6% (95% CI 4.2-4.9%) in Mali and 4.2% (95% CI 3.5-4.9%) in Nigeria. Controlling for age, sex and clustering, the OR of TF for school-attendees compared to non-attendees was 0.64 (95% CI 0.56-0.73) in Ethiopia, 0.67 (95% CI 0.56-0.80) in Mali, 1.03 (95% CI 0.81-1.16) in Niger and 1.06, (95% CI 0.65-1.73) in Nigeria.; Estimating the prevalence of trachoma through examination of only school-going children risks underestimating the true prevalence.

Diagnosis of soil-transmitted helminths such as Strongyloides stercoralis and hookworms (Ancylostoma duodenale and Necator americanus) is challenging due to irregular larval and egg output in infected individuals and insensitive conventional diagnostic procedures. Sensitive novel real-time PCR assays have been developed. Our study aimed to evaluate the real-time PCR assays as a diagnostic tool for detection of Strongyloides spp. and hookworms in a random stool sample of 218 asymptomatic schoolchildren in Cambodia. Overall prevalence of 17.4% (38/218) and 34.9% (76/218) were determined by real-time PCR for Strongyloides stercoralis and hookworms, respectively. Sensitivity and specificity of Strongyloides stercoralis specific real-time PCR as compared to the combination of Baermann/Koga Agar as gold standard were 88.9% and 92.7%, respectively. For hookworm specific real-time PCR a sensitivity of 78.9% and specificity of 78.9% were calculated. Co-infections were detectable by PCR in 12.8% (28/218) of individuals. Strongyloides stercoralis real-time PCR applied in asymptomatic cases showed a lower sensitivity compared to studies undertaken with symptomatic patients with the same molecular tool, yet it proved to be a valid supplement in the diagnosis of STH infection in Cambodia.

Background We assessed the risk of helminth infections in association with the use of wastewater and excreta in agriculture in Hanam province, northern Vietnam. In two cross-sectional surveys, we obtained samples from 1,425 individuals from 453 randomly selected households. Kato-Katz thick smear and formalin-ether concentration techniques were used for helminth diagnosis in two stool samples per person. Socio-demographic and water, sanitation and hygiene related characteristics, including exposure to human and animal excreta and household wastewater management, were assessed with a questionnaire. Results Overall 47% of study participants were infected with any helminth (Ascaris lumbricoides 24%, Trichuris trichiura 40% and hookworm 2%). Infections with intestinal protozoa were rare (i.e. Entamoeba histolytica 6%, Entamoeba coli 2%, Giardia lamblia 2%, Cryptosporidium parvum 5% and Cyclospora cayetanensis 1%). People having close contact with polluted Nhue River water had a higher risk of helminth infections (odds ratio [OR] = 1.5, 95% confidence interval [CI] 1.1–2.2) and A. lumbricoides (OR = 2.1, 95% CI 1.4–3.2), compared with those without contact. The use of human excreta for application in the field had an increased risk for a T. trichiura infection (OR = 1.5, 95% CI 1.0–2.3). In contrast, tap water use in households was a protective factor against any helminth infection (i.e. T. trichiura OR = 0.6, 95% CI 0.4–0.9). Prevalences increased with age and males had generally lower prevalences (OR = 0.8, 95% CI 0.6–1.0), participants performing agricultural (OR = 1.5, 95% CI 1.1–2.1) and having a low educational level (OR = 1.7, 95% CI 1.2–2.4) were significantly associated with helminth infections. None of the factors related to household's sanitary condition, type of latrine, household's SES, use of animal excreta, and personal hygiene practices were statistically significant associated with helminth infection. Conclusions Our study suggests that in agricultural settings, direct contact with water from Nhue River and the use of human excreta as fertiliser in the fields are important risk factors for helminth infection. Daily use of clean water is likely to reduce the risk of worm infection. Deworming policies and national programs should give more attention to these agricultural at risk populations.

Human intestinal sarcocystosis (HIS), caused by Sarcocystis species, is acquired by eating undercooked meat from sarcocyst-containing cattle (S. hominis, S. heydorni) and pigs (S. suihominis). We report on the detection of human intestinal Sarcocystis infections in a cross-sectional survey of Strongyloides stercoralis in early 2014, in Rovieng District, Preah Vihear Province, northern Cambodia. Among 1081 participants, 108 (10.0%) were diagnosed with Sarcocystis spp. oocysts in stool samples. Males had a significantly higher risk of infection than females (OR: 1.9, 95% CI: 1.3-2.9, p=0.001). None of the reported symptoms (abdominal discomfort, diarrhea, muscle pain and itching skin) occurring in the two weeks preceding the examinations were associated with a Sarcocystis infection. Many Sarcocystis cases were found among those who had participated in a wedding celebration and Chinese New Year festivities, where they had consumed raw or insufficiently cooked beef (83.3%) and pork (38.9%) based dishes. This report documents the first HIS cases in Cambodia.

Praziquantel is the only drug available for the treatment of Opisthorchis viverrini infections. Tribendimidine has emerged as a potential treatment alternative; however, its pharmacokinetic (PK) properties have not been sufficiently studied to date. Via two phase IIa dose-finding studies, 68 O. viverrini patients were treated with 25- to 600-mg doses of tribendimidine using 50- and 200-mg tablet formulations. Plasma, blood, and dried blood spots (DBS) were sampled at selected time points. The two main metabolites of tribendimidine, active deacetylated amidantel (dADT) and acetylated dADT (adADT), were analyzed in plasma, blood, and DBS. PK parameters were estimated by noncompartmental analysis. An acceptable agreement among plasma and DBS concentrations was observed, with a mean bias of ≤10%, and 60% dADT and 74% adADT concentrations being within ±20% margins. We found that 200-mg tribendimidine tablets possess immediate floating characteristics, which led to variable time to maximal concentration of drug ( T max ) values (2 to 24 h) between individuals. Dose proportionality was observed for dADT from 25 to 200 mg using 50-mg tablets, but at higher dosages (200 to 600 mg), saturation occurred. The median ratio of the area under the plasma concentration-time curve from 0 to 24 h (AUC 0–24 ) of dADT to the AUC 0– 24 of adADT ranged from 0.8 to 26.4, suggesting substantial differences in acetylation rates. Cure rates ranged from 11% (25-mg dose) to 100% (400-mg dose). Cured patients showed significantly higher dADT maximal serum concentrations ( C max ) and AUC 0–24 values than uncured patients. Tribendimidine is a promising drug for the treatment of opisthorchiasis. However, the tablet formulation should be optimized to achieve consistent absorption among patients. Further studies are warranted to assess the large differences between individuals in the rate of metabolic turnover of dADT to adADT. (This study has been registered with the ISRCTN Registry under no. ISRCTN96948551.)

Summary Background Treatment of the liver fluke infection Opisthorchis viverrini relies exclusively on praziquantel. Tribendimidine could be an alternative treatment option. We aimed to assess the efficacy and safety of ascending single, oral doses of tribendimidine in patients with O viverrini infection. Methods We did two randomised, parallel-group, single-blind, dose-ranging, phase 2 trials in children (aged 8–14 years) and adults and adolescents (≥15 years) in three O viverrini endemic villages in Champasack province, southern Laos. Patients with O viverrini infection were randomly assigned, via a computer-generated central block-randomisation procedure, with block sizes of three (study 1) and four, eight, and 12 (study 2), to receive oral tribendimidine at doses of 200 mg, 400 mg, or 600 mg in a 1:1:1 ratio (adults and adolescents in study 1); 25 mg, 50 mg, 100 mg, or 200 mg (four 50 mg tablets) in a 1:1:1:1 ratio (adults and adolescents in study 2); or 100 mg, 200 mg, or 400 mg in a 1:1:1 ratio (children in study 1). One non-randomised group of children received tribendimidine 50 mg (study 2). Participants, investigators, and laboratory technicians doing the diagnostic assessments were masked to group assignment, but the investigator administering treatment could have recognised the treatment group based on the number of tablets. The primary objective was to estimate the dose–response relation in terms of cure rate and egg reduction rate. We did available-case analysis of all patients with primary endpoint data. We predicted dose–response associations with E max models. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN96948551. Findings Between Oct 25, 2012, and Nov 5, 2013, 318 adolescents and adults were randomly assigned to seven tribendimidine dose groups: 200 mg (n=51), 400 mg (n=49), or 600 mg (n=47) in study 1, and 25 mg (n=39), 50 mg (n=47), 100 mg (n=44), or 200 mg (four 50 mg tablets; n=41) in study 2. 128 children were randomly assigned to receive tribendimidine 100 mg (n=44), 200 mg (n=40), or 400 mg (n=44) in study 1; 39 children were enrolled and received tribendimidine 50 mg in study 2. In adolescents and adults, the number of patients cured increased with increasing tribendimidine doses up to 100 mg: ten of 39 patients (25·6%, 95% CI 13·0–42·1) were cured in the 25 mg group, 20 of 47 patients (42·6%, 28·3–57·8) were cured in the 50 mg group, and 34 of 44 patients (77·3%, 62·2–88·5) were cured in the 100 mg group; geometric mean egg reduction rates were 86·9% (95% CI 74·8–93·4), 95·9% (92·7–97·7), and 99·1% (98·2–99·7), respectively. The 200 mg dose resulted in cure in 40 of 47 (83·0%, 69·2–92·5) adolescents and adults given the 200 mg tablet and 25 of 41 (61·0%, 95% CI 44·5–75·8) of those given four 50 mg tablets; the 400 mg dose resulted in cure in 43 of 47 patients (91·5%, 79·6–97·6) and the 600 mg dose resulted in cure in 36 of 45 patients (80·0%, 65·4–90·4). Corresponding egg reduction rates were 99·8% (95% CI 99·7–100·0) with one 200 mg tablet, 97·9% (95·9–99·2) with four 50 mg tablets, 99·9% (99·8–100·0) with 400 mg, and 99·8% (99·6–99·9) with 600 mg. The E max model predicted an egg reduction rate of 99·0% (95% CI 95·7–99·8) at 111 mg in adolescents and adults. 50 mg tribendimidine had moderate efficacy in children, with cure recorded in 16 of 39 patients (41·0%, 95% CI 25·6–57·9). The 100 mg dose resulted in cure in 40 of 44 children (98·9%, 95% CI 78·3–97·5) and an egg reduction rate of 99·7% (95% CI 99·0–100·0), with no increased efficacy at higher doses. The E max model predicted an egg reduction rate of 99·0% (95% CI 92·2–99·9) at 215 mg. Few adverse events were reported and were mostly mild, with few moderate and no serious events. The most common adverse events 3 h after treatment in adolescents and adults were vertigo (n=35 [11%]), headache (n=9 [3%]), nausea (n=6 [2%]), and fatigue (n=4 [1%]), and in children were headache (n=3 [2%]), vertigo (n=2 [1%]), and fatigue (n=2 [1%]). Interpretation Tribendimidine has excellent efficacy and tolerability at doses of 100 mg and above. Our study included mainly adults and children with low-intensity O viverrini infection; future studies should assess the efficacy of tribendimidine in patients with infections of moderate and high intensity. Funding Department for International Development, Medical Research Council, Wellcome Trust Joint Global Health Trials Scheme.

Opisthorchiasis is a neglected tropical disease, yet it is of considerable public health importance in Southeast Asia given the predilection for chronically infected persons to develop cholangiocarcinoma. We evaluated a handheld microscope for the diagnosis of Opisthorchis viverrini in a community-based setting in Lao People's Democratic Republic in comparison with conventional light microscopy. In stool samples collected from 104 individuals, handheld microscopy revealed a sensitivity of 70.6% and a specificity of 89.5% for O. viverrini infection. Pearson's correlation for quantitative fecal egg counts between the two devices was 0.98 (95% confidence interval: 0.98-0.99). With small adjustments to further increase diagnostic sensitivity, a handheld microscope may become a helpful tool to screen for O. viverrini and other helminth infections in public health settings.

Background Strongyloides stercoralis is the only soil-transmitted helminth with the ability to replicate within its host, leading to long-lasting and potentially fatal infections. It is ubiquitous and its worldwide prevalence has recently been estimated to be at least half that of hookworm. Information on the epidemiology of S. stercoralis remains scarce and modalities for its large-scale control are yet to be determined. Methodology/Principal Findings A community-based two-year cohort study was conducted among the general population in a rural province in North Cambodia. At each survey, participants infected with S. stercoralis were treated with a single oral dose of ivermectin (200μg/kg BW). Diagnosis was performed using a combination of the Baermann method and Koga agar plate culture on two stool samples. The cohort included participants from eight villages who were either positive or negative for S. stercoralis at baseline. Mixed logistic regression models were employed to assess risk factors for S. stercoralis infection at baseline and re-infection at follow-up. A total of 3,096 participants were examined at baseline, revealing a S. stercoralis prevalence of 33.1%. Of these participants, 1,269 were followed-up over two years. Re-infection and infection rates among positive and negative participants at baseline were 14.4% and 9.6% at the first and 11.0% and 11.5% at the second follow-up, respectively. At follow-up, all age groups were at similar risk of acquiring an infection, while infection risk significantly decreased with increasing village sanitation coverage. Conclusions/Significance Chemotherapy-based control of S. stercoralis is feasible and highly beneficial, particularly in combination with improved sanitation. The impact of community-based ivermectin treatment on S. stercoralis was high, with over 85% of villagers remaining negative one year after treatment. The integration of S. stercoralis into existing STH control programs should be considered without further delay., Author Summary Strongyloides stercoralis is an intestinal parasite that can replicate within its host, leading to long-lasting and potentially life-threatening infections. Occurring worldwide, it thrives where the climate is warm and sanitation is poor. S. stercoralis is not well detected by standard field techniques and its global prevalence is largely underestimated. Strongyloidiasis is arguably the most neglected of neglected tropical diseases. No control strategy currently exists for it. Ongoing control programs against other similar parasites regularly deliver treatment that has little effect on S. stercoralis. This parasite is a major public health issue in Cambodia, where prevalence rates of up to 40% were recently found. We diagnosed, treated and followed-up (over two years) more than 1,200 villagers in rural Cambodia to assess the impact of ivermectin on S. stercoralis at community level and assess whether S. stercoralis control could be integrated into existing programs. Our results indicate that ivermectin treatment was highly beneficial, with more than 85% of participants testing negative one year after treatment. All ages were at similar risk of acquiring an infection. The effect of community-based treatment was enhanced by increasing village sanitation coverage. We conclude that S. stercoralis control is feasible and strategies should be designed without further delay.

Background Praziquantel (PZQ) is the treatment of choice for infections with the liver fluke Opisthorchis viverrini, a major health problem in Southeast Asia. However, pharmacokinetic (PK) studies investigating the disposition of PZQ enantiomers (R- and S-PZQ) and its main metabolite, R-trans-4-OH-PZQ, in diseased patients are lacking. The implementation of a dried blood spot (DBS) sampling technique would ease the performance of PK studies in remote areas without clinical facilities. The aim of the present study is to provide data on the disposition of PZQ enantiomers and R-trans-4-OH-PZQ in opisthorchiasis patients and to validate the use of DBS compared to plasma and blood sampling. Methodology/Principal Findings PZQ was administered to nine O. viverrini-infected patients at 3 oral doses of 25 mg/kg in 4 h intervals. Plasma, blood and DBS were simultaneously collected at selected time points from 0 to 24 h post-treatment. PK parameters were determined using non-compartmental analysis. Drug concentrations and areas under the curve (AUC0–24h) measured in the 3 matrices were compared using Bland-Altman analysis. We observed plasma AUC0–24hs of 1.1, 9.0 and 188.7 μg/ml*h and half-lives of 1.1, 3.3 and 6.4 h for R-PZQ, S-PZQ and R-trans-4-OH, respectively. Maximal plasma concentrations (Cmax) of 0.2, 0.9 and 13.9 μg/ml for R-PZQ, S-PQZ and R-trans-4-OH peaked at 7 h for PZQ enantiomers and at 8.7 h for the metabolite. Individual drug concentration measurements and patient AUC0–24hs displayed ratios of blood or DBS versus plasma between 79–94% for R- and S-PZQ, and between 108–122% for R-trans-4-OH. Conclusions/Significance Pharmacodynamic (PD) in vitro studies on PZQ enantiomers and R-trans-4-OH-PZQ are necessary to be able to correlate PK parameters with efficacy. DBS appears to be a valid alternative to conventional venous sampling for PK studies in PZQ-treated patients., Author Summary Opisthorchiasis, caused by the food-borne trematode Opisthorchis viverrini, affects more than 8 million people in Southeast Asia, and in its chronic phase it might lead to cholangiocarcinoma. Praziquantel (PZQ) is the sole drug available to treat the disease and is administered as a racemic mixture of R and S enantiomers, of which R-PZQ is considered active. As PZQ is rapidly metabolized, its disposition and efficacy in patients might considerably vary according to disease state, sex or age. However, pharmacokinetic (PK) studies on the disposition of PZQ enantiomers and its main metabolite, R-trans-4-OH, in diseased patients are lacking. To allow the collection of PK samples in a large number of patients, we implemented a dried blood spot (DBS) technique, which is less invasive than venipuncture. The aim of our study is to provide first data on the disposition of PZQ enantiomers and the main metabolite of PZQ in opisthorchiasis patients and to validate the use of DBS over venous sampling. Standard PZQ treatment was administered to nine O. viverrini infected patients, and plasma, blood and DBS were simultaneously collected within 24 h post-treatment. We observed a 100-fold higher disposition of the metabolite compared to R-PZQ, which questions its role in the opisthorchidal activity of PZQ. DBS sampling appears to be a valid alternative to venous sampling and will be a valuable tool for future PK studies in PZQ-treated patients.

Opisthorchiasis, caused by the liver fluke Opisthorchis viverrini, a food-borne trematode, is an important public health problem; however, only a single drug, praziquantel is available. We investigated tribendimidine–praziquantel combinations against O. viverriniin vitro and in vivo. The IC50 values of 0.16 μg/ml and 0.05 μg/ml were determined for praziquantel and tribendimidine, respectively, against adult O. viverriniin vitro. When O. viverrini was exposed to both drugs simultaneously (using a drug ratio based on the IC50 (1:3.2)) a synergistic effect was calculated (combination index (CI) at the IC50= 0.7). A similar result was observed when drug addition in vitro was spaced by the respective half-lives of the drugs (a CI of 0.78 at the IC50 for tribendimidine followed by praziquantel and a CI of 0.47 at the IC50 for praziquantel followed by tribendimidine). In vivo median-effect dose (ED50) values of 191 mg/kg and 147 mg/kg were calculated for praziquantel and tribendimidine, respectively. Low to moderate worm burden reductions (38–62%) were observed in O. viverrini infected hamsters when both drugs were administered simultaneously or on subsequent days, pointing to antagonistic effects in vivo. Further studies are necessary to understand the striking differences between the in vitro and in vivo observations using combinations of praziquantel and tribendimidine on O. viverrini.

Summary Background Many people with epilepsy in low-income countries do not receive appropriate biomedical treatment. This epilepsy treatment gap might be caused by patients not seeking biomedical treatment or not adhering to prescribed antiepileptic drugs (AEDs). We measured the prevalence of and investigated risk factors for the epilepsy treatment gap in rural Kenya. Methods All people with active convulsive epilepsy identified during a cross-sectional survey of 232 176 people in Kilifi were approached. The epilepsy treatment gap was defined as the percentage of people with active epilepsy who had not accessed biomedical services or who were not on treatment or were on inadequate treatment. Information about risk factors was obtained through a questionnaire-based interview of sociodemographic characteristics, socioeconomic status, access to health facilities, seizures, stigma, and beliefs and attitudes about epilepsy. The factors associated with people not seeking biomedical treatment and not adhering to AEDs were investigated separately, adjusted for age. Findings 673 people with epilepsy were interviewed, of whom 499 (74%) reported seeking treatment from a health facility. Blood samples were taken from 502 (75%) people, of whom 132 (26%) reported taking AEDs, but 189 (38%) had AEDs detectable in the blood. The sensitivity and specificity of self-reported adherence compared with AEDs detected in blood were 38·1% (95% CI 31·1–45·4) and 80·8% (76·0–85·0). The epilepsy treatment gap was 62·4% (58·1–66·6). In multivariable analysis, failure to seek biomedical treatment was associated with a patient holding traditional animistic religious beliefs (adjusted odds ratio 1·85, 95% CI 1·11–2·71), reporting negative attitudes about biomedical treatment (0·86, 0·78–0·95), living more than 30 km from health facilities (3·89, 1·77–8·51), paying for AEDs (2·99, 1·82–4·92), having learning difficulties (2·30, 1·29–4·11), having had epilepsy for longer than 10 years (4·60, 2·07–10·23), and having focal seizures (2·28, 1·50–3·47). Reduced adherence was associated with negative attitudes about epilepsy (1·10, 1·03–1·18) and taking of AEDs for longer than 5 years (3·78, 1·79–7·98). Interpretation The sensitivity and specificity of self-reported adherence is poor, but on the basis of AED detection in blood almost two-thirds of patients with epilepsy were not on treatment. Education about epilepsy and making AEDs freely available in health facilities near people with epilepsy should be investigated as potential ways to reduce the epilepsy treatment gap. Funding Wellcome Trust.

Mobile phones provide a low cost method of addressing certain health system needs in developing countries. We examined SMS-supported interventions for prevention, surveillance, management and treatment compliance of communicable and non-communicable diseases in developing countries. We searched both peer-reviewed and grey literature reporting the use of SMS messages for disease prevention, surveillance, self-management and compliance in developing countries. A total of 98 applications fulfilled the inclusion criteria (33 prevention, 19 surveillance, 29 disease management and 17 patient compliance applications). In 31 projects, the SMS applications were evaluated. The majority of applications focused on HIV/AIDS and were located in India, South Africa and Kenya. Most used bulk (push) messaging. In general, they were well accepted by the population. The review provides further evidence that mobile phones are an appropriate and promising tool for disease control interventions in developing countries.

This review highlights the current status and control of liver fluke infections in the Mekong Basin countries where Opisthorchis and Clonorchis are highly endemic. Updated data on prevalence and distribution have been summarized from presentations in the “96 Years of Opisthorchiasis. International Congress of Liver Flukes”. It is disturbing that despite treatment and control programs have been in place for decades, all countries of the Lower Mekong Basin are still highly endemic with O. viverrini and/or C. sinensis as well as alarmingly high levels of CCA incidence. A common pattern that is emerging in each country is the difference in transmission of O. viverrini between lowlands which have high prevalence versus highlands which have low prevalence. This seems to be associated with wetlands, flooding patterns and human movement and settlement. A more concerted effort from all community, educational, public health and government sectors is necessary to successfully combat this fatal liver disease of the poor.

The aim of this study was to develop and validate a tool to measure perceived stigma among people with epilepsy (PWE) in Kilifi, Kenya. We reviewed existing scales that measured stigma, particularly of epilepsy. We conducted a qualitative study to determine salient concerns related to stigma in Kilifi. Themes were generated, and those related to stigma were used to construct an 18-item stigma scale. A descriptive cross-sectional survey was then conducted among 673 PWE to assess the reliability and validity of the scale. Internal consistency was calculated using Cronbach's alpha and test–retest reliability with an interclass correlation coefficient. The final scale had 15 items, which had high internal consistency (Cronbach's α = 0.91) and excellent test–retest reliability (r = 0.92). Factor analysis indicated that the scale was unidimensional with one factor solution explaining 45.8% of the variance. The Kilifi Stigma Scale for Epilepsy is a culturally appropriate measure of stigma with strong psychometric properties., Highlights ► We developed and validated a scale to measure perceived stigma in epilepsy. ► The scale was unidimensional: one factor solution explained 45.8% of the variance.► It had high internal consistency and excellent test-retest reliability. ► It can be adapted and validated for use in other research settings.

Introduction L’epilepsie est une des maladies neurologiques les plus frequentes dans le monde, touchant 70 millions de personnes dont 80 % vivent dans les pays en developpement. Alors que les prevalences en Asie du sud-est (7,7 ‰ au Laos et 5,8 ‰ au Cambodge) sont proches de celle observee en France (6 ‰), l’enjeu de sante publique pour les systemes de soins de ces pays releve avant tout du deficit therapeutique qui est superieur a 95 % au Laos comme au Cambodge. Parmi les determinants de cette situation, l’accessibilite aux centres de sante (distance, frequence et cout des deplacements) est probablement un levier privilegie dans la recherche d’une strategie d’identification et de prise en charge efficace. L’objectif principal de notre programme de recherche etait de mesurer l’efficience d’une nouvelle approche des soins de sante de proximite en testant deux strategies : (1) des visites villageoises mensuelles des personnels des centres de sante (nommes DHV) formes au depistage et au suivi des patients epileptiques au Laos versus (2) une strategie identique ou les missions du DHV etaient assurees par les volontaires de sante residant dans les villages au Cambodge. Methode Ces deux etudes quasi-experimentales d’une duree de 12 mois (realisees en 2015–2016 au Laos et en 2016–2017 au Cambodge) ont ete conduites dans des districts ruraux grâce a une approche comparee entre une zone d’intervention et une zone controle. Notre programme a assure une large campagne d’information, education et communication, des formations specifiques pour les DHV, des enquetes sur les connaissances attitudes et pratiques (CAP) en population generale, et un systeme de collecte des donnees (monitoring) realisee a frequence reguliere. Notre recherche a ainsi permis des analyses comparatives « avant-apres et ici-ailleurs » pour demontrer l’efficacite de l’intervention dans chaque pays, ainsi qu’une comparaison entre les deux strategies d’intervention. Resultats Au Laos, apres 12 mois d’experimentation, le deficit de traitement a baisse de 5,5 % (de 20 a 43 cas sous traitement sur les 418 attendus) dans la zone d’intervention contre 0,5 % (de 21 a 25 cas sous traitement sur les 788 attendus) dans la zone controle (p = 0,0001). Dans la zone d’intervention, 36,1 % des epileptiques ont refuse le traitement, 27,8 % ont prefere etre soigne sans passer par le centre de sante primaire (circuit de proximite) ; et parmi ceux qui ont adhere, le suivi a domicile a permis d’augmenter de 27,6 % le nombre de compliants (p = 0,019). Au Cambodge, apres six mois d’experimentation sur une aire d’etude ou le deficit de traitement etait de 100 %, la strategie a permis de le baisser significativement de 31,1 % (55 cas sur les 177 estimes) dans la zone d’intervention, au regard des 7,0 % de baisse (23 cas sur les 327 estimes) dans la zone controle (p = 0,0001). Incontestablement, la strategie est plus efficace lorsque le DHV reside dans le village. Conclusion Afin de completer ces resultats d’efficacite therapeutique, l’analyse des CAP de la population generale et des personnels de sante, ainsi que l’analyse des itineraires therapeutiques des epileptiques eclaireront nos resultats. D’ores et deja, les points positifs de l’experimentation au Laos ont permis la redaction d’une « Advocacy Policy » (promotion & politique) favorablement accueillis par le ministere de la sante au Laos, comme cela est egalement envisage au Cambodge a la fin de notre intervention en juin 2017.

The current widespread school-based control of soil-transmitted helminth (STH) infections is also advocated for preschool children. The objective of this study was to assess infection with STHs as well as their determinants in preschool children (

Plus de 50 millions de personnes sont atteintes d'epilepsie dans le monde, et 80 % vivent dans les pays en developpement, en particulier tropicaux, ou la transmission des maladies infectieuses est favorisee par des facteurs geographiques, economiques, politiques, sociologiques et culturels. Les maladies infectieuses jouent un role majeur dans l'etiologie des crises d'epilepsie et de l'epilepsie. Environ un quart des epilepsies peuvent etre attribuees a une infection, en particulier a des parasitoses. Il existe toutefois un manque d'information, et la contribution relative de chaque agent pathogene a la charge globale de l'epilepsie reste inconnue. Une association causale entre une affection parasitaire specifique et l'epilepsie chez un patient reste delicate a etablir, car les deux sont frequemment rencontrees dans les pays tropicaux. Des facteurs de risque multiples, des co-infections et des comorbidites peuvent encore compliquer les investigations. Des approches prospectives en recherche sont essentielles pour ameliorer la connaissance dans ce domaine.

PURPOSE: Stigma is a major burden of epilepsy. In sub-Saharan Africa the few studies that addressed epilepsy stigma emphasize enacted, rather than perceived, stigma. This inattention may compromise clinical management and delay help seeking, thereby contributing to the treatment gap. We assessed perceived stigma and identified sociocultural and psychological factors explaining greater stigma among people with epilepsy (PWE) in Benin. METHODS: PWE included in this study were ascertained using a door-to-door survey in the general population in a Beninese rural area. We applied both qualitative and quantitative research methods to assess stigma and patient's experience and beliefs. An Explanatory Model Interview Catalogue (EMIC) and verbally administered questionnaires provided data for demographic, clinical, and sociocultural features. Sociocultural features were evaluated in terms of illness-related experience and sociocultural representations of epilepsy. Depression and anxiety were also screened. RESULTS: Eighty PWE were included. About 68.7% reported feeling stigmatized. Multivariate regression revealed that factors independently associated with perceived stigma were experience of social isolation (p < 0.001), experience of marital problems (p < 0.01), and presence of anxiety disorder (p < 0.01). DISCUSSION: Perceived stigma is an important issue in epilepsy in Benin. Social factors seem to be more influential than sociocultural representation of epilepsy. Insofar as research is needed in other African countries to determine the nature and relevant features of stigma to improve treatment and control.

The treatment and control of opisthorchiasis relies on a single drug, praziquantel; hence, there is a need to develop novel opisthorchicidal drugs. We investigated the in vitro and in vivo activity of the antimalarial mefloquine against Opisthorchis viverrini. Hamsters infected with O. viverrini for 2 weeks (juvenile infections) and 4 weeks (adult infections) were treated orally with single 200-400-mg/kg oral mefloquine. Worm burden reductions were assessed against untreated control hamsters. Worms were incubated in the presence of 10 and 100 microg/ml mefloquine. Scanning electron microscopy was used to examine adult O. viverrini after recovery from hamsters and following in vitro incubation. A single oral dose of 300-mg/kg mefloquine resulted in worm burden reductions of 88.5% (juvenile infection) and 96.0% (adult infections), respectively. Incubation with 10 and 100 microg/ml mefloquine resulted in rapid death of O. viverrini. Extensive tegumental disruption such as blebbing, sloughing, and furrowing was seen on worms incubated in vitro and on flukes recovered 48 h posttreatment. In conclusion, we have documented promising opisthorchicidal activities in hamsters and in vitro with the tegument being an important drug target. Proof-of-concept studies with mefloquine could be considered in opisthorchiasis patients.

Capillaria philippinensis is a rare zoonotic intestinal parasite that emerged in the 1960s. The outcome of intestinal capillariasis may be fatal if untreated in due time. We report three cases of intestinal capillariasis in Lao People's Democratic Republic (Lao PDR). The three patients were unrelated previously healthy young men (24, 26, and 27 years of age) with no underlying disease or immune depression. They had chronic diarrhea, abdominal pain, edema, and severe weight loss. Two of them acquired the infection in Thailand; the other patient had no travel history outside Lao PDR. All patients were seen several times in different hospitals before the diagnosis was made. All had concurrent parasite infections: Giardia lamblia, Entamoeba histolytica, Strongyloides stercoralis, Opisthorchis viverrini, and hookworm. The patients frequently consumed uncooked fish. After treatment with albendazole (400 mg/day for 21-30 days) all patients recovered. In Lao PDR, consumption of raw small freshwater fish is common. Therefore, the possibility of a capillariasis outbreak should be considered.

Distomatoses due to Fasciola spp. and Fasciolopsis buski are very common in the developing countries of Southeast Asia. The flukes in Laos have not yet been completely studied and described, however. In 2004, we began screening for these two distomatoses in the province of Savannakhet, in southern Laos. Our initial results showed that the causal agent of fascioliasis in humans and animals is Fasciola gigantica. The infestation rate of fascioliasis in cattle in slaughterhouses ranged from 17 to 57%, with higher percentages in buffalo (75-100%) than in cows (0-25%). In Laotian villages, the prevalence of human fascioliasis reached 2.4 % after a stool examination and 13.8 % after systematic serology testing. The prevalence of intestinal distomatosis from F. buski was 33.7%. The rate of villagers with hepatobiliary and intestinal events exceeded 2% but the involvement of these two forms of distomatosis varied highly, ranging from 1.7% (stool diagnosis) to 16.4% (serodiagnosis) for F. gigantica and 11.2% for F. buski. We have described the first cases of fascioliasis and intestinal distomatosis from F. buski in Laos.

Hydroelectric projects offer opportunities for infrastructure development and economic growth; yet, if not well designed, implemented and operated, they have the potential to negatively affect the health and well-being of local and distant downstream communities. Remote rural populations are particularly vulnerable to the sudden influx of men, materials and money, and associated population mixing that accompany project construction phases. Two large-scale baseline health surveys, carried out in 2001/2002 in two communities that were affected by the Nam Theun 2 hydroelectric project in central Lao PDR, were analysed. For the population to be resettled on the Nakai plateau it was observed that access to clean water and basic sanitation facilities was lacking. Faecal examinations revealed a high infection prevalence for Ascaris lumbricoides (67.7%), but relatively low prevalences for hookworm (9.7%), Taenia spp. (4.8%), Enterobius vermicularis (4.4%), Trichuris trichiura (3.9%), Strongyloides stercoralis (1.4%) and Opisthorchis viverrini (0.9%). For the population in the Xe Bang Fai downstream area, rapid diagnostic tests for malaria carried out in the rainy season found a prevalence below 1%, which might be explained by the complete coverage of households with insecticide-treated nets (99.8%). Anthropometric measurements in both populations suggest that wasting, stunting and underweight in under 5-year-old children were moderate to high; 15.9-17.5%, 40.4-55.7% and 35.8-55.7%, respectively. One out of six individuals aged above 14 years were malnourished, most likely as a result of early childhood wasting. Moderate anaemia, assessed by age- and sex-specific haemoglobin levels, was present in 43.8% (Nakai) and 54.9% of the individuals examined (Xe Bang Fai). Several indicators were extracted that can be utilised for monitoring changes in health, well-being and equity, as the project is implemented and operated.

Severe liver disease due to Schistosoma mekongi was frequent in northern Cambodia. Between 1995 and 2002, seven rounds of mass chemotherapy (praziquantel) reduced infection from 50% to below 3%. In 2002, we assessed hepatosplenic morbidity by historical, clinical and ultrasonographic investigations in adults (older than 14 years) from endemic (n = 342) and non-endemic (n = 103) areas (Kratie province). Clinical hepatomegaly (25 vs. 0%), splenomegaly (55 vs. 0%), reported blood in stool (41 vs. 20%) and abdominal pain (78 vs. 57%) were significantly higher in the endemic area. In this area, significantly more subjects reported a family history of death due to schistosomiasis (12 vs. 0%); 63% (vs. 0%) reported having at least three treatments of praziquantel in previous years; and only 11% (vs. 99%) had normal liver ultrasonographic examination. Periportal fibrosis with portal hypertension was diagnosed in 46% (vs. 0%) of people in this area; 18% (vs. 0%) and 5% (vs. 0%) of portal hypertension was classified as moderate and severe, respectively. People aged between 24 and 35 years were mostly affected. There was no gender difference. The pathology in the endemic district is most probably residual morbidity of S. mekongi infections. Contributions of co-infections (hepatitis) cannot be excluded. Careful monitoring of the affected communities is required

International audience; Epilepsy is a significant, but often underappreciated, health problem in Asia. Here, we systematically review the literature on epidemiology, aetiology, and management of epilepsy in 23 Asian countries. Prevalence estimates are available for only 11 countries from door-to-door surveys and are generally low. Figures for annual incidence in China and India are similar to those in the USA and Europe but lower than those reported from Africa and Latin America. There is a peak in incidence and prevalence in childhood, but a second peak in elderly people, as seen in developed countries, has not been documented. The main causes are head injuries, cerebrovascular disease, CNS infections, and birth trauma. Availability of epilepsy care depends largely on economic factors. Imaging and neurophysiological facilities are available in most countries, but often only in urban centres. Costly drugs, a large treatment gap, limited epilepsy surgery, and negative public attitude to epilepsy are other notable features of management in Asia. An understanding of the psychosocial, cultural, economic, organisational, and political factors influencing epilepsy causation, management, and outcome should be of high priority for future investigations.

Summary In Cambodia, schistosomiasis is transmitted in the provinces of Kratie and Stung Treng where approximately 80 000 individuals are estimated to be at risk of infection. The baseline prevalence of infection was estimated to be between 73% and 88%, and cases of severe morbidity (hepatosplenomegaly, puberty retardation) and mortality were very common. In 1994, the Ministry of Health of Cambodia started schistosomiasis control applying universal chemotherapy with praziquantel (40 mg/kg). The coverage of the programme was between 62% and 86% for 8 years. This simple control measure resulted in the control of the disease: no cases were reported in 2004 and only three cases were reported in 2005. In addition, there are no longer reports of cases of severe morbidity due to schistosomiasis. Since the beginning of the control programme, a single dose of mebendazole (500 mg) has been combined with praziquantel during the mass chemotherapy; as a result the prevalence of Ascaris lumbricoides and hookworms dropped from 74.5% to 10% and from 86% to 40% respectively. The experience in Cambodia demonstrates that, with political commitment, control of parasitic diseases is achievable even in a situation of minimal resources. The programme represents a successful model for other developing countries.

Background The mean age of acute dengue has undergone a shift towards older ages. This fact points towards the relevance of assessing the influence of age-related comorbidities, such as diabetes, on the clinical presentation of dengue episodes. Identification of factors associated with a severe presentation is of high relevance, because timely treatment is the most important intervention to avert complications and death. This review summarizes and evaluates the published evidence on the association between diabetes and the risk of a severe clinical presentation of dengue. Methodology/Findings A systematic literature review was conducted using the MEDLINE database to access any relevant association between dengue and diabetes. Five case-control studies (4 hospital-based, 1 population-based) compared the prevalence of diabetes (self-reported or abstracted from medical records) of persons with dengue (acute or past; controls) and patients with severe clinical manifestations. All except one study were conducted before 2009 and all studies collected information towards WHO 1997 classification system. The reported odds ratios were formally summarized by random-effects meta-analyses. A diagnosis of diabetes was associated with an increased risk for a severe clinical presentation of dengue (OR 1.75; 95% CI: 1.08–2.84, p = 0.022). Conclusions/Significance Large prospective studies that systematically and objectively obtain relevant signs and symptoms of dengue fever episodes as well as of hyperglycemia in the past, and at the time of dengue diagnosis, are needed to properly address the effect of diabetes on the clinical presentation of an acute dengue fever episode. The currently available epidemiological evidence is very limited and only suggestive. The increasing global prevalence of both dengue and diabetes justifies further studies. At this point, confirmation of dengue infection as early as possible in diabetes patients with fever if living in dengue endemic regions seems justified. The presence of this co-morbidity may warrant closer observation for glycemic control and adapted fluid management to diminish the risk for a severe clinical presentation of dengue., Author Summary Both dengue and diabetes have reached epidemic dimensions and pose a joint threat to a large proportion of populations in low- and middle-income countries. Dengue is no longer a disease primarily affecting children. Therefore the influence of non-communicable diseases such as diabetes, which are increasingly prevalent in adults, on the clinical presentation of a dengue episode becomes a public health priority. We conducted a systematic literature review to assess the available evidence on the effect of diabetes mellitus (DM) on the clinical presentation of dengue. The meta-analysis of published evidence combined with supporting biological evidence point to an increased risk for potentially life threatening symptoms of dengue among patients with diabetes. The current evidence is limited by statistical power and other study limitations and does not allow conclusions about a causal effect of diabetes. Yet, based on the currently available evidence, diabetes patients with fever and living in a dengue endemic region should seek confirmation of dengue infection as early as possible. Diabetes should be considered in the triage of patients for close observation and early intervention, which are challenges, particularly during dengue outbreaks. Timeliness of intervention is the most important factor averting serious complications and death in patients with acute dengue.