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Background Cholangiocarcinoma (CCA), a fatal bile duct cancer, has a high incidence in Western Siberia, Russian Federation. In addition, Opisthorchis felineus, a bile duct–dwelling trematode liver fluke is highly endemic. Closely related species have been shown to be cancerogenic agents in Asia. We therefore examined the association between O felineus infection and CCA in Western Siberia. Methods We conducted a hospital-based, individually matched case-control study between January 2017 and August 2020 in Tomsk Oblast and Khanty-Mansiysk Autonomous Okrug, Yugra, Russian Federation. Histologically confirmed CCA patients (cases) were compared with matched age, sex, and place of residence hospital controls. The examination of study participants included the diagnosis of current and past O felineus infection, abdominal ultrasonographical assessment, physical examination, and interview on exposures to potential risk factors. Results We identified 40 patients with CCA and 160 controls. Exposures to O felineus infection was strongly associated with CCA (odds ratio [OR], 3.9; 95% confidence interval [CI], 1.4–10.8; P = .008). Also, cases reported more often that they were currently or in the past were infected by O felineus compared with controls (OR, 4.03; 95% CI, 1.7–9.5; P = .001). Furthermore, cases reported river fish consumption and fishing habits significantly more often than controls (OR, 5.5; 95% CI, 1.5–19.8; P = .009 and OR, 3.3; 95% CI, 1.4–7.7; P = .005). Conclusions The study results revealed a strong significantly increased risk for CCA development in O felineus–infected individuals. Elaboration of the guidelines on screening programs for early CCA diagnosis, prevention, and treatment is socially important in endemic regions.

Hookworms are the most common parasitic nematodes in the genus of Ancylostoma that infect both humans and animals in subtropical and tropical South East Asia. The common hookworm species in cats is Ancylostoma ceylanicum which is emerging in Thailand. However, the genetic characterization of hookworms in cats is outdated and insufficiently studied in Thailand. We aimed to investigate the prevalence, risk factors and genetic characterization of hookworm infection in semi-domesticated temple cats in Bangkok, Thailand. A total of 500 temple cat fecal samples were collected from 43 monasteries in 24 districts of Bangkok, Thailand. Polymerase Chain Reaction (PCR) was performed by amplifying the internal transcribed spacer (ITS) gene and mitochondrial cytochrome oxidase c subunit I (cox 1) gene. The infection prevalence of hookworm in temple cats was 13.2% (66/500). The highest prevalence was 34.6% in the Bang Khun Thian district, which is located in a suburban area. The risk factor analysis revealed that cats older than one year (OR 2.4, 95% CI 1.1–5.5, p < 0.05), lack of veterinary attention (OR 2.9, 95% CI 1.7–4.9, p < 0.001) and Bangkok zone (suburban vs. inner city; OR 2.9, 95% CI 1.6–5.4, p < 0.001) were significantly increasing hookworm infection risk. All hookworm positive samples were identified as A. ceylanicum by ITS gene. Moreover, genetic characterization of cox 1 gene in A. ceylanicum isolates indicated a mix of isolates from humans, cats and dogs. The findings show that temple cats can act as a potential source of zoonotic hookworm parasites for the human and animal population in Bangkok, Thailand. Therefore, appropriate control measures for hookworms in semi-domesticated temple cats as well as prevention measures for hookworms in pet cats and humans should be promoted.

Background The point-of-care circulating cathodic antigen (POC-CCA) test is increasingly used as a rapid diagnostic method for Schistosoma mansoni infection. The test has good sensitivity, although false positive results have been reported among pregnant women and patients with urine infections and hematuria. We validated the POC-CCA test’s ability to diagnose Schistosoma mekongi infection in Lao People’s Democratic Republic (Lao PDR), where S. mekongi is endemic. Of particular interest was the test’s specificity and possible cross-reactivity with other helminth infections. Methods We conducted a cross-sectional study of children and adults in the provinces of Champasack (Schistosoma mekongi and Opisthorchis viverrini endemic), Savannakhet (O. viverrini endemic) and Luang Prabang (soil-transmitted helminths endemic) between October 2018 and April 2019. POC-CCA and urine dipstick tests were administered to all study participants, while an additional pregnancy test was offered to women. Two stool samples were collected from participants and examined with a Kato-Katz test (two smears per stool). Logistic regression was used to associate potential confounding factors (predictors) with POC-CCA test results (outcome). Results In S. mekongi-endemic Champasack, 11.5% (n = 366) and 0.5% (n = 2) of study participants had positive POC-CCA and Kato-Katz test results, respectively. Only one of the two Kato-Katz positive patients was also POC-CCA positive. In Champasack and Luang Prabang, where S. mekongi is not endemic, the POC-CCA test yielded (presumably) false positive results for 6.0% (n = 22) and 2.5% (n = 9) of study participants, respectively, while all of the Kato-Katz tests were negative. POC-CCA positive test results were significantly associated with O. viverrini infection (1.69, 95% confidence interval (CI): 1.02–2.77, P = 0.042), increased leukocytes (adjusted Odds Ratio (aOR) = 1.58, 95% CI: 1.15–2.17, P = 0.005) and hematuria (aOR = 1.50, 95% CI: 1.07–2.10, P = 0.019) if the observed trace was counted as a positive test result. Two pregnant women from Champasack province had POC-CCA positive tests. Conclusions We observed a cross-reaction between the POC-CCA test and O. viverrini infection. To some extent, we can confirm previous observations asserting that POC-CCA provides false positive results among patients with urinary tract infections and hematuria. In S. mekongi-endemic areas, POC-CCA can be applied cautiously for surveillance purposes, keeping in mind the considerable risk of false positive results and its unknown sensitivity.

Background Schistosomiasis, an acute and chronic parasitic disease caused by human pathogenic Schistosoma species, is a neglected tropical disease affecting more than 220 million people worldwide. For diagnosis of schistosomiasis, stool and urine microscopy for egg detection is still the recommended method, however sensitivity of these methods is limited. Therefore, other methods like molecular detection of DNA in stool, detection of circulating cathodic antigen in urine or circulating anodic antigen in urine and serum, as well as serological tests have gained more attention. This study examines the sensitivity and specificity of a rapid diagnostic test based on immunochromatography (Schistosoma ICT IgG-IgM, LD Bio, Lyon, France) for simultaneous detection of specific IgG and IgM antibodies in serum, against Schistosoma spp. in endemic and non-endemic populations. Methodology/Principal findings Frozen banked serum samples from patients with confirmed schistosomiasis, patients with other helminth infections, patients with seropositive rheumatoid arthritis and healthy blood donors were used to assess the sensitivity and the specificity of the Schistosoma ICT IgG-IgM rapid diagnostic test. The test showed a sensitivity of 100% in patients with parasitologically confirmed schistosomiasis, irrespective of the species (S. mansoni, S. haematobium, S. japonicum, S. mekongi). In healthy blood donors and patients with rheumatoid factor positive rheumatoid arthritis from Europe, specificity was 100%. However, in serum samples of patients with other tissue invasive helminth infections, the test showed some cross-reactivity, resulting in a specificity of 85%. Conclusion/Significance With its high sensitivity, the Schistosoma ICT IgG-IgM rapid diagnostic test is a suitable screening test for detection of Schistosoma specific antibodies, including S. mekongi. However, in populations with a high prevalence of co-infection with other tissue invasive helminths, positive results should be confirmed with other diagnostic assays due to the test’s imperfect specificity.

Cholangiocarcinoma (CCA) is a cancer with high mortality owing to its aggressiveness and resistance to therapy. The liver flukes of the Opisthorchiidae family have been recognized as risk factors of CCA. Opisthorchis felineus infection occurs in Western Siberia, the biggest endemic area in the Russian Federation, and is associated with chronic inflammation of the bile ducts, which may be linked to severe hepatobiliary morbidity. We report two cases of confirmed CCA who had a chronic O. felineus infection. Both cases presented unspecific symptoms at the onset of the disease, a stage when severe pathological changes already had occurred. Both patients were living in endemic areas but did not receive any antihelminthic treatment. This report underlines the need for assessment of O. felineus infection as a causative factor of CCA. The results will provide further arguments for control of O. felineus in the Russian Federation.

Background Severe hepatosplenic complications arise in patients with chronic Schistosoma mansoni infection after heavy exposure to disease agents in endemic areas. These complications are rarely reported and, hence, underestimated. Case presentation We report on eight patients with severe morbidity associated with S. mansoni infection in Ituri Province, northeastern Democratic Republic of Congo (DRC). The patients were identified during a community-based survey in 2017; one patient was seen at the district hospital. After taking the patients’ history, a clinical examination and an abdominal ultrasonographical examination were performed. S. mansoni infection was diagnosed in fecal (Kato-Katz technique) and urine (point-of-case circulating cathodic antigen test) samples. These eight patients with severe intestinal and hepatosplenic complications were identified from four villages with high S. mansoni infection prevalence and related morbidity. The patients’ ages ranged from 19 to 57 years; four patients were women. Three patients reported hematemesis. Two patients were severely anemic. All patients reported non-specific abdominal symptoms, such as diarrhea (six patients), abdominal pain (seven patients), and blood in the stool (five patients), as well as weight loss (two patients). Abdominal ultrasonography revealed ascites in four patients. All patients had portal hypertension with hepatomegaly (seven patients) or splenomegaly (five patients). Of the six patients with a discernable liver parenchyma pattern, five displayed pattern F and three patient displayed pattern E. Liver parenchyma was not visible for two patients with severe ascites. An S. mansoni infection was confirmed in six patients, with infection intensity ranging from light to heavy. All S. mansoni positive patients were treated with praziquantel (40 mg/kg body weight) and referred to the district hospital for follow-up. One patient with severe ascites died two weeks after we saw her. Due to security and accessibility reasons, the villages could not be visited again and the patients were lost to follow-up. Conclusions Our observations of patients with severe schistosomiasis document the severe degree of endemicity of S. mansoni in the province and suggest an urgent need for adequate schistosomiasis control measures that target vulnerable population groups and address severe complications.

To reach zero dog-related human rabies deaths by 2030, Liberia must prioritize rabies as a public health threat. Understanding dog demography parameters are imperative and sets the basis for planning cost-effective and sustainable mass dog vaccination programs nationwide. We conducted a cross-sectional household survey in eleven rural districts of Bong and one urban district of Montserrado County to gather baseline information on the canine population, human-mediated dog movements, people's relationships and practices towards dogs, and further information to estimate costs for a nationwide campaign. In total, 1282 respondents were interviewed (612 rural and 670 urban). About 34% of the rural and 37% of the urban households owned at least one dog. The canine: human ratios were 1:6.1 in the rural and1:5.6 in the urban area and did not differ notably among both counties. The estimated canine population for Liberia is 594,640. The majority of respondents (55%) reported poor waste disposal. Muslims were less likely to own a dog than Christians (39% vs 19% OR: 0.4 95% CI: 0.2-0.6) (p0.001). Six percent of respondents mentioned that a family member was exposed to a dog bite in the past year, and most victims were adult males. Four of the victims reportedly died after showing rabies compatible symptoms. Twenty-seven percent of dog-owning households in rural areas reported that at least one dog originated from urban areas, and 2% of urban households brought in dogs from another country. In addition, 43% of respondents consumed dog meat at least once. Fifty percent of the respondents claimed knowledge of rabies but only 5.7% and 1.9% mentioned rabies transmission through rabies-infected saliva and rabies-infected mucus on broken skin. Forty percent of the respondents did not know whether rabies was incurable in humans once clinical signs appear. Assuming 30 vaccinators could vaccinate 50 dogs per day for eighteen months (371 working days), the total cost for the vaccination of the national Liberian canine population is estimated at 1.6 million (USD) for one vaccination round. Our study reveals an overall poor disease knowledge and the potential for spread of rabies in the study areas. A nationwide rabies awareness is crucial to enhance rabies prevention and control through mass dog vaccination.

Background: Epilepsy affects more than 50 million people worldwide, 80% of whom live in low- and middle-income countries (LMICs). In Southeast Asia, the prevalence is moderate (6‰), and the main public health challenge is reducing the treatment gap, which reaches more than 90% in rural areas. Methods: This 12-month comparative study (intervention vs. control areas) assessed the community effectiveness of two different strategies for the identification and home follow-up of people with epilepsy by Domestic Health Visitors for epilepsy (DHVes). In Lao PDR, DHVes were health center staff covering several villages via monthly visits; in Cambodia, DHVes were health volunteers living in the villages. Findings: At baseline, the treatment gap was >95% in Lao PDR and 100% in Cambodia. After 12 months, the treatment gap in Lao PDR decreased by 5·5% (range: 4·0–12·2) in the intervention area and 0·5% (range: 0·4–0·8) in the control area (p

Background The liver fluke, Opisthorchis felineus, is widely distributed throughout Europe and large parts of the Russian Federation. In Western Siberia, information about opisthorchiasis is lacking although infection may lead to severe liver and bile duct diseases. We aimed to assess the current prevalence of O. felineus infection along with associated risk factors and morbidity in rural Western Siberia. Methods We conducted a community-based, cross-sectional study in the rural Shegarskiy district, Tomsk Oblast, Russian Federation. All household members (≥ 7 years) present on the survey day were enrolled (n = 600). Two stool samples per person were examined for helminth eggs, using PARASEP (DiaSys Ltd, UK). The number of eggs per gram (EPG) of feces was recorded. Each study participant was interviewed to determine risk factors, using a pre-tested questionnaire. An abdominal ultrasonography examination of liver and bile ducts was performed with a mobile, high resolution ultrasound device. In total, 488 persons completed assessments (two stool samples, completed questionnaires); of those, 436 individuals had an ultrasonography (US) examination. Results We observed a prevalence of O. felineus infection of 60.2%. Significant risk factors for infection were the consumption of river fish (odds ratio from adjusted analysis [aOR] 2.4, 95% CI 1.52–3.95, p, Author summary Opisthorchis felineus is a trematode (liver fluke) that infects the hepatobiliary systems of humans in endemic regions. The infection may lead to severe liver and bile duct diseases, making it a public health issue in endemic communities like Western Siberia. Yet, little information is available from this region about its epidemiology. We aimed to assess the current prevalence of O. felineus infection along with associated risk factors and morbidity in one district in rural Western Siberia. We conducted a cross-sectional community-based study in the Shegarskiy district, Tomsk Oblast, Russian Federation. All household members (≥ 7 years) present on the survey day were enrolled (n = 600). Two stool samples per person were examined for helminth eggs. We interviewed study participants to determine risk factors using a questionnaire. An abdominal ultrasonography examination was performed to assess liver and bile duct pathology. In total, 488 persons completed assessments. We found a high O. felineus infection prevalence of 60.2%. Women and older study participants had a higher risk of infection. The consumption of river fish, particularly stock, smoked, frozen and raw fish; and fishing activities increased the risk of infection. Study participants with a higher socio-economic status had a lower risk of infection. The ultrasonography showed that participants with infection had an increased risk of gallbladder stones and bile duct pathologies. Our study provides valuable information about Opisthorchis infection prevalence, its risk factors and morbidity in rural Siberia. The results will be useful for developing a multidisciplinary, community-based control program against Opisthorchis infection in endemic regions.

Strongyloidiasis is a common neglected tropical disease in tropical and sub-tropical climatic zones. At the worldwide level, there is high uncertainty about the strongyloidiasis burden. This uncertainty represents an important knowledge gap since it affects the planning of interventions to reduce the burden of strongyloidiasis in endemic countries. This study aimed to estimate the global strongyloidiasis prevalence. A literature review was performed to obtain prevalence data from endemic countries at a worldwide level from 1990 to 2016. For each study, the true population prevalence was calculated by accounting for the specificity and the sensitivity of testing and age of tested individuals. Prediction of strongyloidiasis prevalence for each country was performed using a spatiotemporal statistical modeling approach. The country prevalence obtained from the model was used to estimate the number of infected people per country. We estimate the global prevalence of strongyloidiasis in 2017 to be 8.1% (95% CI: 4.2&ndash, 12.4%), corresponding to 613.9 (95% CI: 313.1&ndash, 910.1) million people infected. The South-East Asia, African, and Western Pacific Regions accounted for 76.1% of the global infections. Our results could be used to identify those countries in which strongyloidiasis prevalence is highest and where mass drug administration (MDA) should be deployed for its prevention and control.

Background Reducing morbidity is the main target of schistosomiasis control efforts, yet only rarely do control programmes assess morbidity linked to Schistosoma sp. infection. In the Democratic Republic of Congo (DRC), and particularly in north-eastern Ituri Province, little is known about morbidity associated with Schistosoma mansoni infection. For this reason, we aimed to assess intestinal and hepatosplenic morbidity associated with S. mansoni infection in Ituri Province. Methods/Principal findings In 2017, we conducted a cross-sectional study in 13 villages in Ituri Province, DRC. S. mansoni infection was assessed with a Kato-Katz stool test (2 smears) and a point-of-care circulating cathodic antigen (POC-CCA) urine test. A questionnaire was used to obtain demographic data and information about experienced intestinal morbidity. Each participant underwent an abdominal ultrasonography examination to diagnose hepatosplenic morbidity. Of the 586 study participants, 76.6% tested positive for S. mansoni. Intestinal morbidity reported in the two preceding weeks was very frequent, and included abdominal pain (52.7%), diarrhoea (23.4%) and blood in the stool (21.5%). Hepatosplenic morbidity consisted of abnormal liver parenchyma patterns (42.8%), hepatomegaly (26.5%) and splenomegaly (25.3%). Liver pathology (adjusted odds ratio [aOR] 1.20, 95% confidence interval [CI] 1.06–1.37, p = 0.005) was positively and significantly associated with S. mansoni infection. Hepatomegaly (aOR 1.52, 95% CI 0.99–2.32, p = 0.053) and splenomegaly (aOR 1.12, 95% CI 0.73–1.72, p = 0.619) were positively but not significantly associated with S. mansoni infection at the individual level. At the village level, S. mansoni prevalence was positively associated with the prevalence of hepatomegaly and splenomegaly. High-intensity S. mansoni infections were associated with diarrhoea, blood in the stool, hepatomegaly, splenomegaly, and liver parenchyma (C, D, E and F pathology patterns). Four study participants were diagnosed with ascites and five reported hematemesis. Conclusions/Significance Our study documents a high burden of intestinal and hepatosplenic morbidity associated with S. mansoni infection status in Ituri Province. The findings call for targeted interventions to address both S. mansoni infection and related morbidity., Author summary Schistosomiasis caused by Schistosoma mansoni is of great public health importance in sub-Saharan Africa. The World Health Organization (WHO) recommends that control efforts aim to reduce morbidity through large-scale intervention programmes. However, intestinal and liver morbidity is rarely assessed in such control programmes. Hence, little is known about (i) the magnitude of the intestinal and liver morbidity burden in the community, or about (ii) the morbidity associated with S. mansoni infection, specifically. We conducted a cross-sectional study in which we assessed intestinal morbidity by questionnaire and liver morbidity by abdominal ultrasonography. Additionally, we determined the infection status of the study participants using standard diagnostic procedures (Kato-Katz technique and point-of-care cathodic circulating S. mansoni antigen [POC-CCA] urine test). Among the 586 study participants, aged six years and older, from 13 villages in Ituri Province, DRC, we observed a high degree of intestinal (23.4% with diarrhoea; 21.5% with blood in stool) and hepatosplenic morbidity (42.8% with abnormal liver C, D, E, and F patterns; 26.5% with an enlarged liver; 25.3% with an enlarged spleen). S. mansoni infection was associated with liver and spleen enlargement. Likewise, S. mansoni infection intensity was linked to diarrhoea, to liver and spleen enlargement and to pathological changes in the liver parenchyma. At village level, we observed that the prevalence of an enlarged liver and spleen among patients increased with the prevalence of S. mansoni infection. We conclude that the population of Ituri Province carries an alarming burden of intestinal, liver and spleen morbidity associated with S. mansoni infection. A comprehensive control programme to address this infection and disease burden is urgently required.

Background: Hookworm disease is endemic throughout many parts of the Asia Pacific, despite targeted control programs of at-risk populations. The success of these programs has been hindered by the limited efficacy of widely-used mebendazole, rapid re-infection rates linked to persistent reservoirs of untreated people and dogs, and the low sensitivity of conventional coprodiagnostic techniques employed. Methods: Here, we used standard faecal flotation (SFF) and a multiplex qPCR (mqPCR) assay to calculate and compare species-specific cure and egg reduction rates of single dose albendazole (400 mg) against hookworm infections at community level. Data from a cross-sectional survey in 1,232 people from Cambodia were used to inform a generalised linear mixed model to identify risk factors linked to hookworm infection(s) at baseline. Furthermore, we calculated risk factors associated to the probability of being cured after albendazole administration. Findings: Overall, 13.5% of all 1,232 people tested by SFF were positive for hookworm infection(s). Most (80.1%) infected people were >12 years of age, hence above the age targeted by the WHO control program. We estimate that as age increases, the odds of being infected increases at a faster rate for females than for males. We revealed a substantial difference in cure rate of hookworm infection(s) following albendazole treatment using the SFF (81.5%) and mqPCR (46.4%) assays, and provide the first data on the efficacy of this drug against the zoonotic hookworm Ancylostoma ceylanicum. We estimated that as age increases by one year, the odds of being cured decreases by 0.4%-3.7%. Similarly, the odds of being cured for people who boiled drinking water was estimated to be between 1.02 and 6.82. Interpretation: These findings show that the adoption of refined diagnostic techniques is central to monitoring hookworm infection(s) and the success of control strategies, which can ultimately aid in reducing associated morbidity in human populations. The approach taken is likely to be directly applicable to other parts of Southeast Asia and the Western Pacific, where specific epidemiological conditions might hamper the success of targeted treatment programs. Funding: Faculty of Veterinary and Agricultural Sciences Strategic Research Funds, The University of Melbourne.

The potential health benefits of combined agricultural, nutrition, water, sanitation, and hygiene (WASH) interventions are poorly understood. We aimed to determine whether complementary school garden, nutrition, and WASH interventions reduce intestinal parasites and improve school children’s nutritional status in two regions of Burkina Faso. A cluster-randomized controlled trial was conducted in the Plateau Central and Center-Ouest regions of Burkina Faso. A total of 360 randomly selected children, aged 8–15 years, had complete baseline and end-line survey data. Mixed regression models were used to assess the impact of the interventions, controlling for baseline characteristics. The prevalence of intestinal parasitic infections decreased both in intervention and control schools, but the decrease was significantly higher in the intervention schools related to the control schools (odds ratio [OR] of the intervention effect = 0.2, 95% confidence interval [CI] = 0.1–0.5). Indices of undernutrition did not decrease at end-line in intervention schools. Safe handwashing practices before eating and the use of latrines at schools were significantly higher in the intervention schools than in the control schools at end-line (OR = 6.9, 95% CI = 1.4–34.4, and OR = 14.9, 95% CI = 1.4–153.9, respectively). Parameters of water quality remained unchanged. A combination of agricultural, nutritional, and WASH-related interventions embedded in the social–ecological systems and delivered through the school platform improved several child health outcomes, including intestinal parasitic infections and some WASH-related behaviors. Sustained interventions with stronger household and community-based components are, however, needed to improve school children’s health in the long-term.

Opisthorchis felineus (O. felineus) occurs in Western Siberia and many other parts of the Russian Federation (RF). The true extent of its distribution is not known. Chronic infection may lead to severe hepatobiliary morbidity. According to surgical and experimental reports, long-term infestation might significantly increase the risk for cholangiocarcinoma (CCA). To date, no association between O. felineus infection and CCA has been demonstrated. The objective of this study was to review existing health data on the incidence of O. felineus infection and on the incidence of CCA in the RF. We reviewed the official medical statistics on reported O. felineus infection and CCA in 83 political/geographical units of the RF, covering the period January 2011-December 2013. Annual incidence data were obtained from Rospotrebnadzor and from official medical statistics. We calculated the average annual incidence of infection and cancer. The average annual incidence of O. felineus was 24.7±9.0 cases per 100,000 population. The highest incidence was observed in Khanty-Mansiysk district (599.7 cases per 100,000 population per year). In 27 geographical units, no O. felineus cases were reported. The incidence of liver and intrahepatic bile duct cancers was 4.8±0.2 cases per 100,000 population; the highest rate was reported in Sakha Republic and Tomsk Oblast (14.5 and 9.3 cases per 100,000 population), and the lowest in Yamalo-Nenets Autonomous Okrug (0.9 cases per 100,000 population). O. felineus incidence was not associated with the mean annual incidence of liver and intrahepatic bile duct cancers (r=0.20, p=0.07). This study documents the importance of opisthorchiasis in certain endemic areas and presents the best available data on associations between O. felineus infection and liver/intrahepatic bile duct cancers in RF. The findings support the need to implement a public health control programme against liver fluke infections and to increase the availability of anthelmintic treatment. Further studies are warranted to assess the contribution of opisthorchiasis to the CCA in RF.

Cholangiocarcinoma (CCA) poses a significant public health problem in Southeast Asia, with chronic Opisthorchis viverrini infection being the main risk factor. Epidemiological data on CCA is not available for Lao People Democratic Republic (Lao PDR), though there is a high prevalence of O. viverrini infection in the country. A hospital record-based retrospective study was carried out in six referral hospitals (four in the capital city, one in Savannakhet, one in Pakse) to assess the number of suspected CCA cases admitted between January 2006 and December 2010. In total, we identified 274 patients with liver lesions suggesting CCA, as diagnosed by ultrasound and CT scan. Male gender and age 50years and above were main characteristics of those identified. The majority were admitted to hospitals in the central (58.0%) and southern (29.6%) parts of Lao PDR. Abdominal pain (48.5%) and jaundice (14.2%) were the main symptoms leading to hospitalisation. Some 267 (97.4%) patients had dilated bile ducts; 40 (74.1%) had gallstone or intrahepatic stone, and 33 (12.0%) had a parasitologically confirmed O. viverrini infection. This study provides the first estimated numbers of suspected CCA cases admitted to selected hospitals in Lao PDR. Definitive diagnosis of CCA was not possible. Therefore, case diagnosis and registration of suspected CCA cases are warranted to gather evidence for a national burden estimate of CCA, to develop large-scale studies and adequate preventive and curative health services. A cancer registry would be a most useful tool.

Infections with Strongyloides stercoralis are of considerable public health relevance. Moxidectin, a well-established drug in veterinary medicine under consideration for regulatory submission for the treatment of onchocerciasis, might serve as an alternative to the widely used ivermectin.; We conducted an exploratory, randomized, single-blind trial to evaluate the efficacy and safety of moxidectin (8 mg) vs ivermectin (200 μg/kg) against S. stercoralis infections. Cure rate (CR) against S. stercoralis was the primary outcome. Safety and efficacy against coinfections with soil-transmitted helminths and Opisthorchis viverrini were secondary outcomes. Noninferiority required the lower limit of the 95% confidence interval (CI) of the differences in CRs not exceed 7 percentage points.; A total of 127 participants were enrolled and randomly assigned to the 2 treatments whereby 1 participant per arm was lost to follow-up. We observed a CR of 93.7% (59/63) for moxidectin compared to 95.2% (59/62) for ivermectin. Differences between CRs were estimated as -1.5% percentage points (95% CI, -9.6 to 6.5), thus the lower limit of the CI exceeds the noninferiority margin of 7 percentage points. No side effects were observed. CRs against hookworm infection were 57% (moxidectin) and 56% (ivermectin). Low efficacy for both drugs against O. viverrini was observed.; Moxidectin might be a safe and efficacious alternative to ivermectin for the treatment of S. stercoralis infection, given that only slight differences in CRs were observed. However, noninferiority could not be demonstrated. Larger clinical trials should be conducted once the drug is marketed.; Current Controlled Trials: ISRCTN11983645.

In 2006, some 7 years after the halt of a multi-year schistosomiasis control programme, a study was conducted in the southern part of Lao People's Democratic Republic to determine the morbidity associated with Schistosoma mekongi and concurrent helminth infection. In two S. mekongi-endemic districts, Khong and Mounlapamok, 640 individuals aged 9-40 years were randomly selected. Two stool samples were obtained from each participant and subjected to the Kato-Katz technique for helminth diagnosis. Morbidity was assessed by clinical examination and abdominal ultrasonography. Multiple logistic regression analysis was employed to relate S. mekongi infection with morbidity indicators. In Khong district, S. mekongi prevalence was 13-fold higher than in Mounlapamok district (57.7% vs. 4.4%, p 0.001). Likewise, we observed significantly more often palpated hepatomegaly (15.5% vs. 5.4%) and splenomegaly (9.6% vs. 0.4%). Abdominal ultrasonography revealed that, in Khong district, liver and spleen morbidity occurred more frequently (e.g., enlarged left liver lobe: 89.2% vs. 68.7%, p 0.001). Single species infection with S. mekongi was associated with enlarged peri-portal vein (adjusted odds ratio (aOR) 47.7, 95% confidence interval (CI) 4.2-85.7, p = 0.002), as was S. mekongi-Opisthorchis viverrini co-infection (aOR 2.2, 95% CI 1.1-4.5, p = 0.020). In conclusion, our study shows that in 2006, several years after the halt of the Lao schistosomiasis control programme that emphasised preventive chemotherapy, S. mekongi infection again had reached high prevalence rates. Infection with S. mekongi was associated with substantial hepatosplenic morbidity. Schistosomiasis control measures were re-instigated in 2010. In view of the ultimate goal to eliminate schistosomiasis, rigorous surveillance and public health responses tailored to the social-ecological settings and long-term programme commitment are warranted.

The areas endemic for schistosomiasis in the Lao People’s Democratic Republic and in Cambodia were first reported 50 and 60 years ago, respectively. However, the causative parasite Schistosoma mekongi was not recognized as a separate species until 1978. The infection is distributed along a limited part of the Mekong River, regulated by the focal distribution of the intermediate snail host Neotricula aperta. Although more sensitive diagnostics imply a higher figure, the current use of stool examinations suggests that only about 1500 people are presently infected. This well-characterized setting should offer an exemplary potential for the elimination of the disease from its endemic areas; yet, the local topography, reservoir animals, and a dearth of safe water sources make transmission control a challenge. Control activities based on mass drug administration resulted in strong advances, and prevalence was reduced to less than 5% according to stool microscopy. Even so, transmission continues unabated, and the true number of infected people could be as much as 10 times higher than reported. On-going control activities are discussed together with plans for the future.

Background Strongyloides stercoralis is a neglected soil-transmitted helminth that occurs worldwide, though it is particularly endemic in tropical and subtropical areas. It can cause long-lasting and potentially fatal infections due to its ability to replicate within its host. S. stercoralis causes gastrointestinal and dermatological morbidity. The objective of this study was to assess the S. stercoralis infection risk and, using geostatistical models, to predict its geographical distribution in Cambodia. Methodology / Principal findings A nation-wide, community-based parasitological survey was conducted among the Cambodian population, aged 6 years and older. S. stercoralis was diagnosed using a serological diagnostic test that detects IgG antibodies in urine. Data on demography, hygiene and knowledge about helminth infection were collected. S. stercoralis prevalence among 7,246 participants with a complete data record was 30.5%, ranging from 10.9% to 48.2% across provinces. The parasite was ubiquitous in Cambodia; only five south-eastern provinces had prevalence rates below 20%. Infection risk increased with age for both men and women, although girls under the age of 13 and women aged 50 years and over had lower odds of infection than their male counterparts. Open defecation was associated with higher odds of infection, while having some knowledge of the health problems caused by worms was a protective factor. Infection risk was positively associated with nighttime maximum temperature, minimum rainfall, and distance to water; it was negatively associated with land occupied by rice fields. Conclusions / Significance S. stercoralis infection is rampant in Cambodia. Control programs delivering ivermectin are needed to manage the parasite. However, the high cost of this drug in Cambodia currently precludes the implementation of control initiatives. Donations, subsidies or affordable generics are needed so that S. stercoralis, which infects almost a third of the Cambodian population, can be addressed through an adequate control program., Author summary The threadworm, Strongyloides stercoralis, is a highly neglected worm infection, transmitted through infective larvae in the soil. Threadworms occur worldwide, particularly in tropical climates. It may cause long-lasting and potentially fatal infections due to the parasite’s ability to replicate within its host. This study aimed to assess the risk of threadworm infection at national level in Cambodia. We conducted a nation-wide, community-based parasitological survey of the Cambodian population, aged 6 years and over. The threadworm was diagnosed using a serological diagnostic test that detects antibodies in urine. Data on demography, hygiene and knowledge about helminth infection were collected. The purpose of this study was to predict the risk of S. stercoralis infection in unsurveyed locations, assess risk factors for infection, and map its geographical distribution in Cambodia. About one third (30.5%) of the enrolled study participants (n = 7,246) were infected with threadworms. At provincial level, the lowest and highest infection rates were 10.9% and 48.2%, respectively. Prevalence rates below 20% were found in just five south-eastern provinces. The risk of a threadworm infection increased with age for both men and women. Open defecation was associated with higher risk of infection, while having some knowledge of the health problems caused by worms was a protective factor. Infection risk was positively associated with environmental factors, such as nighttime maximum temperature, minimum rainfall, and distance to water; it was negatively associated with land occupied by rice fields. Threadworm infection is highly prevalent in Cambodia and adequate control measures, including access to treatment, are warranted to address the burden of this Neglected Tropical Disease (NTD) in Cambodia.

There is a pressing need for alternative treatments against the liver fluke Opisthorchis viverrini . Oral tribendimidine is a promising candidate, but its population pharmacokinetic properties are unknown. Two phase IIa trials were conducted in Laos in O. viverrini -infected adults receiving single oral doses of 25 to 600 mg tribendimidine administered as different formulations in each study (study 1 used 200-mg tablets, and study 2 used 50-mg tablets). Venous whole blood, plasma, and capillary dried blood spots were sampled frequently from 68 adults, and concentrations of the tribendimidine metabolites dADT (deacetylated amidantel) and adADT (acetylated dADT) were measured. Population pharmacokinetics were assessed by using nonlinear mixed-effects modeling. The relationship between drug exposure and cure (assessed at 21 days posttreatment) was evaluated by using univariable logistic regression. A six-transit compartment absorption model with a one-disposition compartment for each metabolite described the data well. Compared to the 50-mg formulation (study 2), the 200-mg formulation (study 1) had a 40.1% higher mean transit absorption time, a 113% higher dADT volume of distribution, and a 364% higher adADT volume of distribution. Each 10-year increase in age was associated with a 12.7% lower dADT clearance and a 21.2% lower adADT clearance. The highest cure rates (≥55%) were observed with doses of ≥100 mg. Higher dADT, but not adADT, peak concentrations and exposures were associated with cure ( P = 0.004 and 0.003, respectively). For the first time, population pharmacokinetics of tribendimidine have been described. Known differences in the 200-mg versus 50-mg formulations were captured by covariate modeling. Further studies are needed to validate the structural model and confirm covariate relationships. (This study has been registered with the ISRCTN Registry under no. ISRCTN96948551.)

Chronic infection with Schistosoma mekongi may result in severe hepatosplenic morbidity. We report on eight patients with severe morbidity due to S. mekongi infection. The patients were diagnosed, treated and followed-up between 2007 and 2010 in Khong district, Southern Lao People's Democratic Republic (Lao PDR), eight years after the end of a control intervention. S. mekongi control programmes aimed to prevent morbidity and mortality associated with infection. The patients were visited and interviewed annually. In addition, clinical and abdominal ultrasound examinations were performed and faecal and blood samples were examined. The patients' ages ranged from 6 to 66 years. Of the eight patients, three were children and five were adults. The four youngest patients (aged 6-27 years) significantly improved after praziquantel treatment. One patient (age 46 years) worsened between 2007 and 2010. Two patients died due to bleeding of the oesophageal varices. One patient was lost to follow-up. The leading clinical signs were ascites, splenomegaly, collateral veins on the abdomen and a poor general nutrition status. Ultrasonography disclosed advanced liver fibrosis patterns in all patients; in seven patients, fibrosis pattern E or F was revealed, as per the Niamey protocol (pattern A normal, pattern B to F pathological with increasing severity). Stool microscopy revealed that five patients were co-infected with hookworm and Opisthorchis viverrini. The youngest patient (aged 6 years) was born after the schistosomiasis control program had ended. From her severe morbidity, we can conclude that S. mekongi transmission was on-going in Khong district, and that even in areas with low S. mekongi transmission intensities, severe morbidity from schistosomiasis can develop quickly. Early diagnosis and treatment are imperative, and close monitoring is required.

Hookworm disease caused by; Necator americanus; ,; Ancylostoma duodenale; , and; Ancylostoma ceylanicum; affects half a billion people worldwide. The prevalence and intensity of infection of individual hookworm species are vital for assessing morbidity and generating targeted intervention programs for their control. The present study aims to evaluate a multiplex real-time quantitative PCR (qPCR) assay to determine the prevalence and egg intensity of all three hookworm species and compare this with standard microscopy and published genus-based conventional and real-time multiplex qPCRs. Performance of the diagnostic assays was evaluated using DNA extracted from 192 fecal samples collected as part of a soil-transmitted helminth (STH) survey in northern Cambodia. The prevalence of hookworms as detected by the multiplex hookworm qPCR of 84/192 (43.8%) was significantly higher than that using microscopy of 49/192 (25.5%). The hookworm multiplex qPCR showed very good agreement for the detection of both; N. americanus; (Kappa 0.943) and; Ancylostoma; spp. (Kappa 0.936) with a multiplex STH qPCR. A strong and moderate quantitative correlation between cycle threshold and eggs per gram (EPG) feces was obtained for the hookworm qPCR for seeded DNA egg extracts (; R; 2; ≥ 0.9004) and naturally egg-infected individuals (; R; 2; = 0.6848), respectively. The newly developed hookworm quantitative multiplex qPCR has the potential for application in anthelmintic efficacy trials and for monitoring the success of mass deworming programs targeting individual species of anthroponotic and zoonotic hookworms.

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.

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.

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.

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

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).

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.

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.

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 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 (

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.