Rare human infection with the trematode Echinochasmus japonicus in Lao PDR

Food-borne trematodiases are often neglected although millions of people are affected and these zoonotic diseases are emerging in some parts of the world. Humans acquire an infection through consumption of the second intermediate hosts (e.g. freshwater fish) that harbour the metacercariae of the parasite. Here, we report the first three cases of Echinochasmus japonicus infection in Lao PDR. Adult E. japonicus flukes were recovered from a woman (age: 37 years) and two men (age: 42 and 75 years) following treatment with praziquantel (single oral dose of 40 mg/kg) and purgation (45 ml monosodium sulphate). All three individuals were infected with two other species of trematodes concurrently, namely Opisthorchis viverrini and Haplorchis taichui. The two male patients moreover harboured Prosthodendrium molenkampi and Phaneropsolus bonnei trematodes. All three cases suffered from diarrhoeal episodes and other gastro-intestinal discomforts in the month preceding praziquantel administration and purgation. The frequent consumption of raw or insufficiently cooked freshwater fish and other aquatic products is the root cause of acquiring rare zoonotic infections such as E. japonicus.     

Helminth and intestinal protozoa infections, multiparasitism and risk factors in Champasack province, Lao People's Democratic Republic

Background

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.

Methodology

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.

Principal Findings

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.

Conclusions/Significance

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.     

Low efficacy of single-dose albendazole and mebendazole against hookworm and effect on concomitant helminth infection in Lao PDR

Background

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.

Methodology

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.

Principal Findings

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).

Conclusions/Significance

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.

Clinical Trial Registration

Current Controlled Trials ISRCTN29126001     

Spatial distribution of, and risk factors for, Opisthorchis viverrini infection in southern Lao PDR

Background

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.

Methodology

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.

Principal Findings

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.

Conclusions/Significance

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.     

Long-term outcomes of ivermectin-albendazole versus albendazole alone against soil-transmitted helminths: Results from randomized controlled trials in Lao PDR and Pemba Island,Tanzania

BackgroundPreventive chemotherapy is the cornerstone of soil-transmitted helminth (STH) control. Long-term outcomes and adequate treatment frequency of the recently recommended albendazole-ivermectin have not been studied to date.Methodology/principal findingsDouble-blind randomized controlled trials were conducted in Lao PDR, Pemba Island, Tanzania and Côte d’Ivoire between 2018 and 2020 to evaluate the efficacy and safety of ivermectin-albendazole versus albendazole-placebo in Trichuris trichiura-infected individuals aged 6 to 60. In the framework of this study, in Lao PDR 466 and 413 participants and on Pemba Island, 558 and 515 participants were followed-up six and 12 months post-treatment, respectively. From each participant at least one stool sample was processed for Kato-Katz diagnosis and cure rates (CRs), egg reduction rates (ERRs) and apparent reinfection rates were calculated. If found helminth-positive at six months, participants were re-treated according to their allocated treatment.Long-term outcomes against T. trichiura based on CRs and ERRs of ivermectin-albendazole compared to albendazole were significantly higher at six months in Lao PDR (CR, 65.8 vs 13.4%, difference; 52.4; 95% CI 45.0–60.0; ERRs, 99.0 vs 79.6, difference 19.4; 95% CI 14.4–24.4) and Pemba Island (CR, 17.8 vs 1.4%, difference; 16.4; 95% CI 11.6–21.0; ERRs, 84.9 vs 21.2, difference 63.8; 95% CI 50.6–76.9) and also at 12 months in Lao PDR (CR, 74.0 vs 23.4%, difference; 50.6; 95% CI 42.6–61.0; ERRs, 99.6 vs 91.3, difference 8.3; 95% CI 5.7–10.8) and Pemba Island (CR, 19.5 vs 3.4%, difference; 16.1; 95% CI 10.7–21.5; ERRs, 92.9 vs 53.6, difference 39.3; 95% CI 31.2–47.4) respectively.Apparent reinfection rates with T. trichiura were considerably higher on Pemba Island (100.0%, 95% CI, 29.2–100.0) than in Lao PDR (10.0%, 95% CI, 0.2–44.5) at 12 months post-treatment for participants treated with albendazole alone.Conclusions/significanceThe long-term outcomes against T. trichiura of ivermectin-albendazole are superior to albendazole in terms of CRs and ERRs and in reducing infection intensities. Our results will help to guide decisions on how to best use ivermectin-albendazole in the context of large-scale PC programs tailored to the local context to sustainably control STH infections.Trial registrationClinicalTrials.gov registered with clinicaltrials.gov, reference: {"type":"clinical-trial","attrs":{"text":"NCT03527732","term_id":"NCT03527732"}}NCT03527732, date assigned: 17 May 2018.     

Risk Profiling of Hookworm Infection and Intensity in Southern Lao People’s Democratic Republic Using Bayesian Models

BackgroundAmong 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.MethodologyA 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.Conclusions/SignificanceHookworm 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.     

Diagnosis,Treatment and Risk Factors of Strongyloides stercoralis in Schoolchildren in Cambodia

Background

Worldwide, an estimated 30 to 100 million people are infected with Strongyloides stercoralis, a soil-transmitted helminth. Information on the parasite is scarce in most settings. In semi-rural Cambodia, we determined infection rates and risk factors; compared two diagnostic methods (Koga agar plate [KAP] culture and Baermann technique) for detecting S. stercoralis infections, using a multiple stool examination approach; and assessed efficacy of ivermectin treatment.

Methods/Principal Findings

We performed a cross-sectional study in 458 children from four primary schools in semi-rural villages in Kandal province, using three diagnostic procedures (Kato-Katz, KAP culture and Baermann technique) on three stool samples. Infected children were treated with ivermectin (100 µg/kg/day for two days) and re-examined three weeks after treatment. Hookworm, S. stercoralis, Trichuris trichiura, and small trematode eggs were most prevalent, with 24.4% of children being infected with S. stercoralis. The sensitivity of KAP culture and Baermann technique was 88.4% and 75.0%, respectively and their negative predictive values were 96.4% and 92.5%, respectively. The cumulative prevalence of S. stercoralis increased from 18.6% to 24.4%, after analyzing three stool samples, which was close to the modeled ‘true’ prevalence of 24.8%. Children who reported defecating in latrines were significantly less infected with S. stercoralis than those who did not use latrines (p<0.001). Itchy skin and diarrhea were significantly associated with S. stercoralis infection. The cure rate of ivermectin was 98.3%.

Conclusions/Significance

S. stercoralis infection is highly prevalent among semi-rural Cambodian schoolchildren. The sensitivity of KAP culture is higher than that of the Baermann technique. In the absence of a “gold standard”, analysis of multiple stool samples by different diagnostic methods is required to achieve a satisfactory level of sensitivity. Almost three-quarters of the infections could have been avoided by proper sanitation. Ivermectin is highly efficacious against S. stercoralis but prohibitive costs render the drug inaccessible to most Cambodians.     

Individual responses to a single oral dose of albendazole indicate reduced efficacy against soil-transmitted helminths in an area with high drug pressure

BackgroundAlbendazole (ALB) is administered annually to millions of children through global deworming programs targeting soil-transmitted helminths (STHs: Ascaris lumbricoides, Trichuris trichiura and hookworms, Necator americanus and Ancylostoma duodenale). However, due to the lack of large individual patient datasets collected using standardized protocols and the application of population-based statistical methods, little is known about factors that may affect individual responses to treatment.Methodology/Principal findingsWe re-analyzed 645 individual patient data from three standardized clinical trials designed to assess the efficacy of a single 400 mg oral dose of ALB against STHs in schoolchildren from different study sites, each with varying history of drug pressure based on duration of mass drug administration programs: Ethiopia, low; Lao People’s Democratic Republic (PDR), moderate; Pemba Island (Tanzania), high. Using a Bayesian statistical modelling approach to estimate individual responses (individual egg reduction rates, ERR_i), we found that efficacy was lower in Pemba Island, particularly for T. trichiura. For this STH, the proportion of participants with a satisfactory response (ERR_i ≥50%), was 65% in Ethiopia, 61% in Lao PDR but only 29% in Pemba Island. There was a significant correlation between ERR_i and infection intensity prior to drug administration (ERR_i decreasing as a function of increasing infection intensity). Individual age and sex also affected the drug response, but these were of negligible clinical significance and not consistent across STHs and study sites.Conclusions/SignificanceWe found decreased efficacy of ALB against all the STHs analyzed in Pemba Island (Tanzania), an area with high drug pressure. This does not indicate causality, as this association may also be partially explained by differences in infection intensity prior to drug administration. Notwithstanding, our results indicate that without alternative treatment regimens, program targets will not be achievable on Pemba Island because of inadequate efficacy of ALB.Trial registrationThe study was registered on Clinicaltrials.gov (ID: {"type":"clinical-trial","attrs":{"text":"NCT03465488","term_id":"NCT03465488"}}NCT03465488) on March 7, 2018.