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In this sixth paper of the Series, we review health-financing reforms in seven countries in southeast Asia that have sought to reduce dependence on out-of-pocket payments, increase pooled health finance, and expand service use as steps towards universal coverage. Laos and Cambodia, both resource-poor countries, have mostly relied on donor-supported health equity funds to reach the poor, and reliable funding and appropriate identification of the eligible poor are two major challenges for nationwide expansion. For Thailand, the Philippines, Indonesia, and Vietnam, social health insurance financed by payroll tax is commonly used for formal sector employees (excluding Malaysia), with varying outcomes in terms of financial protection. Alternative payment methods have different implications for provider behaviour and financial protection. Two alternative approaches for financial protection of the non-poor outside the formal sector have emerged—contributory arrangements and tax-financed schemes—with different abilities to achieve high population coverage rapidly. Fiscal space and mobilisation of payroll contributions are both important in accelerating financial protection. Expanding coverage of good-quality services and ensuring adequate human resources are also important to achieve universal coverage. As health-financing reform is complex, institutional capacity to generate evidence and inform policy is essential and should be strengthened.

Plastics debris in the marine environment, including resin pellets, fragments and microscopic plastic fragments, contain organic contaminants, including polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons, petroleum hydrocarbons, organochlorine pesticides (2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane, hexachlorinated hexanes), polybrominated diphenylethers, alkylphenols and bisphenol A, at concentrations from sub ng g1 to g g1. Some of these compounds are added during plastics manufacture, while others adsorb from the surrounding seawater. Concentrations of hydrophobic contaminants adsorbed on plastics showed distinct spatial variations reflecting global pollution patterns. Model calculations and experimental observations consistently show that polyethylene accumulates more organic contaminants than other plastics such as polypropylene and polyvinyl chloride. Both a mathematical model using equilibrium partitioning and experimental data have demonstrated the transfer of contaminants from plastic to organisms. A feeding experiment indicated that PCBs could transfer from contaminated plastics to streaked shearwater chicks. Plasticizers, other plastics additives and constitutional monomers also present potential threats in terrestrial environments because they can leach from waste disposal sites into groundwater and/or surface waters. Leaching and degradation of plasticizers and polymers are complex phenomena dependent on environmental conditions in the landfill and the chemical properties of each additive. Bisphenol A concentrations in leachates from municipal waste disposal sites in tropical Asia ranged from sub g l1 to mg l1 and were correlated with the level of economic development.

Background Prevalence of Opisthorchis viverrini, Schistosoma mekongi and soil-transmitted helminths (STH) remains high in Lao People’s Democratic Republic (Lao PDR), despite control efforts including mass-drug administration, education and communication campaigns. New approaches are required to advance helminth control. Methods An ecohealth study was conducted on two Mekong islands in Southern Laos. Demographic and behavioural data were collected by questionnaire. Human and animal reservoir stools were examined. Bithynia spp. and Neotricula aperta snails were examined using shedding. Fresh water fish were examined using digestion technique. Multivariate random-effects analysis was used to find risk factors associated with helminth infections. Results Human infection rates with O. viverrini, hookworm, S. mekongi, Trichuris trichiura , Ascaris lumbricoides and Taenia spp. were 60.7%, 44.1%, 22.2%, 4.1%, 0.6% and 0.1%, respectively. Heavy intensity infections were 4.2%, 3.6% and 1.8% for O. viverrini , S. mekongi and hookworm, respectively . O. viverrini and S. mekongi infection rates among dogs and cats were 25.0% and 14.7%, respectively. Of the cats tested, 53.1% were infected with O. viverrini . Prevalence of O. viverrini and S. mekongi in snails was 0.3% and 0.01%, respectively. Overall prevalence of O. viverrini infection in fresh water fish was 26.9%, with the highest infection rates occurring in Hampala dispa (87.1%) , Cyclocheilichthys apogon (85.7%) and Puntius brevis (40.0%). Illiteracy and lower socioeconomic status increased the risk of O. viverrini infection, while those aged 10–16 years and possessing latrines at home were less likely to be infected. Household dogs and cats that consumed raw fish were significantly and positively associated with O. viverrini infection of the household members. For S. mekongi , children under 9 years old were exposed significantly to this infection, compared to older age groups. Conclusions There is a pressing need to design and implement an integrated helminth control intervention on the Mekong Islands in southern Lao PDR. Given the highly dynamic transmission of O. viverrini , S. mekongi , STH and extended multiparasitism, annual mass-drug administration is warranted along with environmental modifications, health education and improved access to clean water and adequate sanitation to consolidate morbidity control and move towards elimination. Trail registration number Our findings presented here are from a cross-sectional study, therefore, it has not been registered.

Albendazole and mebendazole are increasingly deployed for preventive chemotherapy targeting soil-transmitted helminth (STH) infections. We assessed the efficacy of single oral doses of albendazole (400 mg) and mebendazole (500 mg) for the treatment of hookworm infection in school-aged children in Lao PDR. Since Opisthorchis viverrini is co-endemic in our study setting, the effect of the two drugs could also be determined against this liver fluke. We conducted a randomized, open-label, two-arm trial. In total, 200 children infected with hookworm (determined by quadruplicate Kato-Katz thick smears derived from two stool samples) were randomly assigned to albendazole (n=100) and mebendazole (n=100). Cure rate (CR; percentage of children who became egg-negative after treatment), and egg reduction rate (ERR; reduction in the geometric mean fecal egg count at treatment follow-up compared to baseline) at 21-23 days posttreatment were used as primary outcome measures. Adverse events were monitored 3 hours post treatment. Single-dose albendazole and mebendazole resulted in CRs of 36.0% and 17.6% (odds ratio: 0.4; 95% confidence interval: 0.2-0.8; P=0.01), and ERRs of 86.7% and 76.3%, respectively. In children co-infected with O. viverrini, albendazole and mebendazole showed low CRs (33.3% and 24.2%, respectively) and moderate ERRs (82.1% and 78.2%, respectively). Both albendazole and mebendazole showed disappointing CRs against hookworm, but albendazole cured infection and reduced intensity of infection with a higher efficacy than mebendazole. Single-dose administrations showed an effect against O. viverrini, and hence it will be interesting to monitor potential ancillary benefits of a preventive chemotherapy strategy that targets STHs in areas where opisthorchiasis is co-endemic. Current Controlled Trials ISRCTN29126001.

Praziquantel is the only drug available for treatment of Opisthorchis viverrini, although in-vivo studies point to activity of mefloquine, artesunate, and tribendimidine against this liver fluke. We aimed to assess the efficacy and safety of these drugs compared with that of praziquantel in patients with O viverrini infection. We did a randomised open-label trial between February and April, 2010, in the Saysetha district, Attapeu Province, Laos. Eligible patients were school children aged 10–15 years who had O viverrini infections. Patients were randomly assigned to one of five different treatment groups by use of a computer-generated randomisation code. We assessed efficacy as cure rate and egg reduction rate in intention-to-treat and per-protocol analyses. The trial was registered with Current Controlled Trials, ISRCTN23425032. 125 children were randomly assigned: 25 received mefloquine, 24 artesunate, 24 mefloquine–artesunate, 27 tribendimidine, and 25 praziquantel. 19 patients were lost to follow-up. In the intention to treat analysis, 14 patients receiving praziquantel were cured compared with none with mefloquine, one with artesunate (odds ratio 0·03, 95% CI 0·004–0·29), one with mefloquine–artesunate (0·03, 0·004–0·29), and 19 with tribendimidine (1·87, 0·60–5·85). Egg reduction rate was 98·4% for praziquantel, 30·2% for mefloquine (egg reduction-rate ratio 1·61, 95% CI 0·21–0·72), 31·5% for artesunate (0·43, 0·23–0·80), 41·3% for mefloquine–artesunate (0·60, 0·31–1·10), and 99·3% for tribendimidine (1·00, 0·44–2·30). Most adverse events were mild or moderate and affected all treatment groups; serious adverse events—vertigo, nausea, vomiting, and anxiety—were reported only by patients taking mefloquine or mefloquine–artesunate. Tribendimidine seems to be at least as efficacious as the drug of choice, praziquantel, for the treatment of O viverrini infections; both drugs were well tolerated. Mefloquine, artesunate, and mefloquine–artesunate did not show an effect. Tribendimidine should be further investigated with large clinical trials. Swiss National Science Foundation, University of Basel.

Opisthorchis viverrini is a food-borne trematode species that might give rise to biliary diseases and the fatal cholangiocarcinoma. In Lao PDR, an estimated 2.5 million individuals are infected with O. viverrini, but epidemiological studies are scarce and the spatial distribution of infection remains to be determined. Our aim was to map the distribution of O. viverrini in southern Lao PDR, identify underlying risk factors, and predict the prevalence of O. viverrini at non-surveyed locations. A cross-sectional parasitological and questionnaire survey was carried out in 51 villages in Champasack province in the first half of 2007. Data on demography, socioeconomic status, water supply, sanitation, and behavior were combined with remotely sensed environmental data and fed into a geographical information system. Bayesian geostatistical models were employed to identify risk factors and to investigate the spatial pattern of O. viverrini infection. Bayesian kriging was utilized to predict infection risk at non-surveyed locations. The prevalence of O. viverrini among 3,371 study participants with complete data records was 61.1%. Geostatistical models identified age, Lao Loum ethnic group, educational attainment, occupation (i.e., rice farmer, fisherman, and animal breeder), and unsafe drinking water source as risk factors for infection. History of praziquantel treatment, access to sanitation, and distance to freshwater bodies were found to be protective factors. Spatial patterns of O. viverrini were mainly governed by environmental factors with predictive modeling identifying two different risk profiles: low risk of O. viverrini in the mountains and high risk in the Mekong corridor. We present the first risk map of O. viverrini infection in Champasack province, which is important for spatial targeting of control efforts. Infection with O. viverrini appears to be strongly associated with exposure to the second intermediate host fish, human behavior and culture, whereas high transmission is sustained by the lack of sanitation.

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. 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 Emax models. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN96948551. 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 Emax 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 Emax 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%]). 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. Department for International Development, Medical Research Council, Wellcome Trust Joint Global Health Trials Scheme.

Detailed investigations of multiparasitism are scarce in the Mekong River basin. We assessed helminth (trematode, nematode, and cestode), and intestinal protozoa infections, and multiparasitism in random population samples from three different eco-epidemiological settings in Champasack province, southern Lao People's Democratic Republic (Lao PDR), and determined underlying risk factors. Two stool samples were collected from 669 individuals aged ≥ 6 months over consecutive days and examined for helminth infections using the Kato-Katz method. Additionally, one stool sample per person was subjected to a formalin-ethyl acetate concentration technique for diagnosis of helminth and intestinal protozoa infections. Questionnaires were administered to obtain individual and household-level data pertaining to behavior, demography and socioeconomic status. Risk factors for hepato-biliary and intestinal parasitic infections and multiparasitism were determined using multiple logistic regressions analyses. MULTIPLE SPECIES INTESTINAL PARASITE INFECTIONS WERE COMMON: 86.6% of the study participants harbored at least two and up to seven different parasites concurrently. Regarding nematode infections, hookworm was the most prevalent species (76.8%), followed by Ascaris lumbricoides (31.7%) and Trichuris trichiura (25.0%). Regarding trematodes, Opisthorchis viverrini and Schistosoma mekongi infections were found in 64.3% and 24.2% of the participants, respectively. Infections with intestinal protozoa were rare. There is a pressing need to intensify and sustain helminth control interventions in the southern part of Lao PDR. Given the high prevalence with nematode and trematode infections and the extent of multiparasitism, preventive chemotherapy is warranted. This intervention should be coupled with health education and improved access to clean water and adequate sanitation to consolidate morbidity control and enhance sustainability.

Infection with hookworm and are serious health problems among children and adolescents in Laos. In this study, we demonstrated the factors related to hookworm and infection, including primary school health programs, among secondary school students in Vientiane city of Laos. A cross-sectional survey and stool examination were conducted among secondary school students in Vientiane. One stool sample from each participant was examined using two Kato-Katz smears. Data of 164 participants were analyzed and the associations among parasitic infections, sociodemographic characteristics, and the school health program in primary school were assessed in a univariate logistic regression analysis. Predictors with <0.25 were retained in a multivariate logistic regression model. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported. The significance level was set at <0.05. The infection rates of and hookworm were 39.0% and 36.0%, respectively. Older students (OR=1.55, 95% CI: 1.01-2.37, =0.046) and those whose father had irregular income (OR=0.47, 95% CI: 0.13-0.93, =0.036) had a higher risk for hookworm infection. Students whose mother had irregular income (OR=0.30, 95% CI: 0.13-0.69, =0.005) had a higher risk for infection. Higher primary school health program scores were associated with a lower risk for hookworm infection in the univariate model but not in the multivariate model. Sociodemographic factors have a strong influence on infections with both hookworm and . Current school health programs in Laos may be insufficient to reduce infections. Other approaches, such as supporting parents in finding employment with regular income, may be needed.

Among the common soil-transmitted helminth infections, hookworm causes the highest burden. Previous research in the southern part of Lao People's Democratic Republic (Lao PDR) revealed high prevalence rates of hookworm infection. The purpose of this study was to predict the spatial distribution of hookworm infection and intensity, and to investigate risk factors in the Champasack province, southern Lao PDR. A cross-sectional parasitological and questionnaire survey was conducted in 51 villages. Data on demography, socioeconomic status, water, sanitation, and behavior were combined with remotely sensed environmental data. Bayesian mixed effects logistic and negative binomial models were utilized to investigate risk factors and spatial distribution of hookworm infection and intensity, and to make predictions for non-surveyed locations. A total of 3,371 individuals were examined with duplicate Kato-Katz thick smears and revealed a hookworm prevalence of 48.8%. Most infections (91.7%) were of light intensity (1-1,999 eggs/g of stool). Lower hookworm infection levels were associated with higher socioeconomic status. The lowest infection levels were found in preschool-aged children. Overall, females were at lower risk of infection, but women aged 50 years and above harbored the heaviest hookworm infection intensities. Hookworm was widespread in Champasack province with little evidence for spatial clustering. Infection risk was somewhat lower in the lowlands, mostly along the western bank of the Mekong River, while infection intensity was homogeneous across the Champasack province. Hookworm transmission seems to occur within, rather than between villages in Champasack province. We present spatial risk maps of hookworm infection and intensity, which suggest that control efforts should be intensified in the Champasack province, particularly in mountainous areas.