Publications by authors named "Somphou Sayasone"

74 Publications

Current status of human liver fluke infections in the Greater Mekong Subregion.

Acta Trop 2021 Sep 10;224:106133. Epub 2021 Sep 10.

Institute of Parasitic Diseases, Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, Guangxi 530021, China.

The Greater Mekong Subregion (GMS) is a trans-national region of the Mekong River basin in Southeast Asia comprising Cambodia, the People's Republic of China (specifically Yunnan Province and Guangxi Zhuang Autonomous Region), Lao People's Democratic Republic (Lao PDR), Myanmar, Thailand, and Vietnam home to more than 340 million people or almost 4.5% of the global population. Human liver fluke infections caused by Opisthorchis viverrini and Clonorchis sinensis have been major public health problems in this region for decades. Opisthorchiasis caused by O. viverrini is prevalent in Thailand, Lao PDR, Cambodia and central-southern Vietnam with more than 12 million people infected. Clonorchiasis caused by C. sinensis is endemic in northern Vietnam and Guangxi with estimated 3.5 -5 million infected. The infections can cause several liver and biliary diseases such as cholangitis, periductal fibrosis, gallstones, and cholangiocarcinoma (CCA), a fatal bile duct cancer. Key determinants of the geographical distribution differences of the two liver fluke species are snail species and geographic barriers. Main risk behaviour of the infections is the culture of eating raw fish "the raw attitude" of people in the GMS, especially the Tai/Dai/Thai/Laos ethnic groups, the major population in the GMS. Over the past 20 years, there is a big change in prevalence of the infections. Opisthorchiasis has long been endemic, particularly in northern and northeastern Thailand and Lao PDR with over 8-10 million cases estimated. However, after several rounds of national campaign against opisthorchiasis using integrated control approach in Thailand over the past three decades, the prevalence of O. viverrini infection has reduced from over 15% in 1996 to 2.2% in 2019. High prevalence of O. viverrini infection continues in Lao PDR and central Vietnam. Emerging high prevalence, up to a maximum of 47.5%, has been noted in Cambodia during the past 10 years possibly due to more studies being conducted rather than increasing prevalence. O. viverrini infection has now also been reported in Lower Myanmar in recent years. Clonorchiasis has been known in northern Vietnam and southern China for a long time. Several surveys have reported infections in Guangxi in the last 10 years, and until now liver fluke infected cases have not been reported in Yunnan. Overall, nowadays, there is a shift in high risk areas for GMS liver fluke infection from northeastern Thailand to Lao PDR, Cambodia, Vietnam, Myanmar, and Guangxi P.R. China. Urgent systematic disease mapping and integrated liver fluke control using One Health approaches should be implemented nationwide in GMS countries.
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http://dx.doi.org/10.1016/j.actatropica.2021.106133DOI Listing
September 2021

Low Sensitivity of Real Time PCRs Targeting Retrotransposon Sequences for the Detection of Complex DNA in Human Serum.

Pathogens 2021 Aug 22;10(8). Epub 2021 Aug 22.

National Reference Centre for Tropical Pathogens, Bernhard Nocht Institute for Tropical Medicine Hamburg, 20359 Hamburg, Germany.

While hybridization probe-based real-time PCR assays targeting highly repetitive multi-copy genome sequences for the diagnosis of complex or complex from human serum are well established, reports on the evaluation of respective assays for the identification of complex DNA in human serum are scarce. Here, we assessed the potential use of the retrotransposon sequences and from , and for the diagnosis of Asian infections. Based on available sequences and newly provided and sequences, hybridization probe-based real-time PCRs targeting and of the complex were designed both as consensus primer assays as well as multi-primer assays for the coverage of multiple variants of the target sequences. The assays were established using plasmids and DNA. While the consensus primer assays failed to detect DNA in human serum samples, the multi-primer assays showed positive or borderline positive results but only in 9.8% (6/61) of serum samples from patients with confirmed infections. Some cross-reactions with samples positive for or were observed but with the -PCR only. In spite of the low sensitivity, the presented experience may guide future evaluations of complex-specific PCRs from human serum.
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http://dx.doi.org/10.3390/pathogens10081067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398367PMC
August 2021

Characterization of the Population Pharmacokinetics of Moxidectin in Adults Infected with Strongyloides Stercoralis: Support for a Fixed-Dose Treatment Regimen.

Clin Pharmacokinet 2021 Jul 23. Epub 2021 Jul 23.

Pediatric Pharmacology and Pharmacometrics Research, University of Basel Children's Hospital (UKBB), Spitalstrasse 33, 4056, Basel, Switzerland.

Background: Moxidectin has recently attracted attention as a novel candidate for the treatment of helminth infections, including Strongyloides stercoralis. This study aims to characterize the population pharmacokinetics (PPK) of moxidectin in S. stercoralis-infected adults using a pharmacometric approach, and to perform model-based simulations to explore different drug dosing strategies.

Methods: A PPK study embedded in a dose-escalation phase IIa trial was conducted in NamBak, Laos. Eight micro blood samples were collected from each of 96 S. stercoralis-infected adults following a moxidectin dose-ranging study, from 2 to 12 mg. A PPK model was developed using nonlinear mixed-effects modeling, and dosing strategies were explored using simulations in S. stercoralis-infected subjects with varying age and body weight (n = 5000 per dosing strategy).

Results: A two-compartment model including delayed absorption with lag-time best described the available PK data. Allometric scaling was applied to account for the influence of body weight. High clearance was found in the infected adults (4.47 L/h [95% confidence interval 3.63-5.39] for a 70 kg individual) compared with that previously reported for healthy adults. Model-based simulations indicated similar variability in mean ± standard deviation area under the curve from time zero to infinity of 1907 ± 1552 and 2175 ± 1670 ng × h/mL in the 60-70 kg weight group, after 8 mg fixed- or weight-based dosing, respectively.

Conclusion: We describe the first PPK model for moxidectin in adults with S. stercoralis infection. Equivalent exposures after fixed-dose and weight-dependent dosing strategies support the use of a simple fixed-dose approach, particularly in large-scale treatment programs.

Trial Registration: Registered at ClinicalTrials.gov (NCT04056325).
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http://dx.doi.org/10.1007/s40262-021-01048-4DOI Listing
July 2021

Low seroprevalence of COVID-19 in Lao PDR, late 2020.

Lancet Reg Health West Pac 2021 Aug 14;13:100197. Epub 2021 Jul 14.

Institut Pasteur du Laos, Vientiane Capital, Lao PDR.

Background: In 2020 Lao PDR had low reported COVID-19 cases but it was unclear whether this masked silent transmission. A seroprevalence study was done August - September 2020 to determine SARS-CoV-2 exposure.

Methods: Participants were from the general community (n=2433) or healthcare workers (n=666) in five provinces and bat/wildlife contacts (n=74) were from Vientiane province. ELISAs detected anti- SARS-CoV-2 Nucleoprotein (N; n=3173 tested) and Spike (S; n=1417 tested) antibodies. Double-positive samples were checked by IgM/IgG rapid tests. Controls were confirmed COVID-19 cases (n=15) and pre-COVID-19 samples (n=265). Seroprevalence for the general community was weighted to account for complex survey sample design, age and sex.

Findings: In pre-COVID-19 samples, 5·3%, [95% CI=3·1-8·7%] were anti-N antibody single-positive and 1·1% [0·3-3·5%] were anti-S antibody single positive. None were double positive. Anti-N and anti-S antibodies were detected in 5·2% [4·2-6·5%] and 2·1% [1·1-3·9%] of the general community, 2·0% [1·1-3·3%] and 1·4% [0·5-3·7%] of healthcare workers and 20·3% [12·6-31·0%] and 6·8% [2·8-15·3%] of bat/wildlife contacts. 0·1% [0·02-0·3%] were double positive for anti-N and anti-S antibodies (rapid test negative).

Interpretation: We find no evidence for significant SARS-CoV-2 circulation in Lao PDR before September 2020. This likely results from early decisive measures taken by the government, social behavior, and low population density. High anti-N /low anti-S seroprevalence in bat/wildlife contacts may indicate exposure to cross-reactive animal coronaviruses with threat of emerging novel viruses.

Funding: Agence Française de Développement. Additional; Institut Pasteur du Laos, Institute Pasteur, Paris and Luxembourg Ministry of Foreign and European Affairs ("PaReCIDS II").
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http://dx.doi.org/10.1016/j.lanwpc.2021.100197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277598PMC
August 2021

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.

PLoS Negl Trop Dis 2021 Jun 30;15(6):e0009561. Epub 2021 Jun 30.

Medical Parasitology and Infection Biology, Helminth Drug Development Unit, Swiss Tropical and Public Health Institute, Basel, Switzerland.

Background: Preventive 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 Findings: Double-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/significance: The 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 Registration: ClinicalTrials.gov registered with clinicaltrials.gov, reference: NCT03527732, date assigned: 17 May 2018.
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http://dx.doi.org/10.1371/journal.pntd.0009561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277064PMC
June 2021

Efficacy and safety of ascending doses of moxidectin against Strongyloides stercoralis infections in adults: a randomised, parallel-group, single-blinded, placebo-controlled, dose-ranging, phase 2a trial.

Lancet Infect Dis 2021 08 30;21(8):1151-1160. Epub 2021 Mar 30.

Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland. Electronic address:

Background: Strongyloidiasis represents a major public health issue, particularly in resource-limited countries. Preliminary studies suggest that moxidectin might serve as an alternative to the only available treatment option, ivermectin. We aimed to evaluate the efficacy and safety of ascending doses of moxidectin in Strongyloides stercoralis-infected patients.

Methods: We did a randomised, parallel-group, single-blinded, placebo-controlled, dose-ranging, phase 2a trial in four villages in northern Laos. Eligible adults (aged 18-65 years) with S stercoralis infection intensities of at least 0·4 larvae per g of stool in at least two stool samples were randomly assigned (1:1:1:1:1:1:1) by use of computerised, stratified, block randomisation into seven treatment groups: 2 mg of moxidectin, 4 mg of moxidectin, 6 mg of moxidectin, 8 mg of moxidectin, 10 mg of moxidectin, 12 mg of moxidectin, or placebo. Participants and primary outcome assessors were masked to treatment allocation, but study site investigators were not. Participants received a single oral dose of their allocated dose of moxidectin in 2 mg tablets, or four placebo tablets. Three stool samples were collected at baseline and two stool samples were collected 28 days after treatment from each participant. A Baermann assay was used to quantify S stercoralis infection and Kato-Katz thick smears were used to qualitatively identify coinfections with additional helminths species. The primary endpoint was cure rate against S stercoralis and was analysed in an available case analysis set, defined as all randomly assigned participants with primary endpoint data. Predicted cure rates and associated CIs were estimated with hyperbolic E models. Safety was evaluated in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04056325, and is complete.

Findings: Between Nov 27, 2019, and March 15, 2020, 785 adults were screened for trial eligibility. Of these, 223 participants were randomly assigned to treatment groups and 209 completed the study and were analysed for the primary outcome. 2 mg of moxidectin had a predicted cure rate of 75% (95% CI 59-87; 22 [73%] of 30 cured) against S stercoralis compared with a predicted cure rate of 14% (5-31; four [14%] of 29 cured) for placebo. With escalating doses, the probability of cure increased from 83% (95% CI 76-88; 26 [90%] of 29 cured) at 4 mg to 86% (79-90; 27 [84%] of 32 cured) at 6 mg, and to 87% (80-92; 24 [83%] of 29 cured) at 8 mg, levelling off at 88% (80-93; 29 [97%] of 30 cured) at 10 mg and 88% (80-93; 26 [87%] of 30 cured) at 12 mg. Moxidectin was well tolerated across all treatment groups, with no serious adverse events being recorded and all reported symptoms being classified as mild.

Interpretation: 4-12 mg of moxidectin showed promising tolerability and efficacy profiles in the treatment of S stercoralis infections in adults. Because 8 mg of moxidectin is used for the treatment of onchocerciasis and has been evaluated for other helminth infections, we recommend this dose for phase 2b and phase 3 trials of strongyloidiasis therapy.

Funding: Fondazione Adiuvare.
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http://dx.doi.org/10.1016/S1473-3099(20)30691-5DOI Listing
August 2021

Assessment of fecal calprotectin and fecal occult blood as point-of-care markers for soil-transmitted helminth attributable intestinal morbidity in a case-control substudy conducted in Côte d'Ivoire, Lao PDR and Pemba Island, Tanzania.

EClinicalMedicine 2021 Feb 30;32:100724. Epub 2021 Jan 30.

Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.

Background: Infections with soil-transmitted helminths (STHs) may result in chronic inflammatory disorders affecting the human host. The objective of this study was to evaluate Fecal Calprotectin (FC) and Fecal Occult Blood (FOB) in individuals infected and non-infected with STHs to identify potential intestinal morbidity markers.

Methods: Stool from participants diagnosed positive for and concomitant STH infections from three countries was used to perform FC and FOB point-of-care assays. Simultaneously, identified STH negative participants underwent FC and FOB testing as controls. Potential associations between test results and determinants were analyzed using multivariable logistic regression.

Findings: In total, 1034 infected cases (mostly light infections) and 157 STH negative controls were tested for FC and FOB. Among all participants tested, 18·5% had ≥ 50 µg/g FC concentration, while 14 (1·2%) were positive for FOB. No statistically significant association was found between infection or co-infection and FC concentration, while an inverse association (odds ratio (OR): 0·45, 95% credible intervals (CrI): 0·26, 0·75) was found between hookworm co-infection and FC concentration. In Lao PDR, the proportion of participants in the ≥ 50 µg/g FC category was significantly higher in the oldest age category compared to the 5-11 years group (OR: 3·31, 95% CrI: 1·62, 7·24). Too few participants were found positive for FOB to derive any conclusions.

Interpretation: Studies are needed to better understand the relationship between intestinal morbidity and STH infections. Suitable, standardized, low-cost markers of STH attributable morbidity to better monitor the impact of STH control interventions are necessary.

Funding: BMGF (OPP1153928).
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http://dx.doi.org/10.1016/j.eclinm.2021.100724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851339PMC
February 2021

Prevalence of pharmacogenomic variants in 100 pharmacogenes among Southeast Asian populations under the collaboration of the Southeast Asian Pharmacogenomics Research Network (SEAPharm).

Hum Genome Var 2021 Feb 4;8(1). Epub 2021 Feb 4.

University of Patras, School of Health Sciences, Department of Pharmacy, Laboratory of Pharmacogenomics and Individualised Therapy, Patras, Greece.

Pharmacogenomics can enhance the outcome of treatment by adopting pharmacogenomic testing to maximize drug efficacy and lower the risk of serious adverse events. Next-generation sequencing (NGS) is a cost-effective technology for genotyping several pharmacogenomic loci at once, thereby increasing publicly available data. A panel of 100 pharmacogenes among Southeast Asian (SEA) populations was resequenced using the NGS platform under the collaboration of the Southeast Asian Pharmacogenomics Research Network (SEAPharm). Here, we present the frequencies of pharmacogenomic variants and the comparison of these pharmacogenomic variants among different SEA populations and other populations used as controls. We investigated the different types of pharmacogenomic variants, especially those that may have a functional impact. Our results provide substantial genetic variations at 100 pharmacogenomic loci among SEA populations that may contribute to interpopulation variability in drug response phenotypes. Correspondingly, this study provides basic information for further pharmacogenomic investigations in SEA populations.
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http://dx.doi.org/10.1038/s41439-021-00135-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862625PMC
February 2021

Development and validation of an LC-MS/MS method for the quantification of the anthelmintic drug moxidectin in a volumetric absorptive microsample, blood, and plasma: Application to a pharmacokinetic study of adults infected with Strongyloides stercoralis in Laos.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Mar 20;1166:122556. Epub 2021 Jan 20.

Swiss Tropical and Public Health Institute, University of Basel, Basel, Switzerland; University of Basel, Basel, Switzerland. Electronic address:

Moxidectin is a promising candidate for addition to the lean repertoire of drugs against neglected tropical diseases (NTD) including strongyloidiasis. Pharmacokinetic (PK) and -dynamic studies are required to support its clinical development. Microsampling approaches enable PK studies in the challenging environments where NTDs are most prevalent, due to simplified collection and processing. We developed a liquid chromatography tandem mass spectrometry method for the sensitive quantification of moxidectin in human blood obtained by capillary sampling with the microsampling device Mitra® compared to blood and plasma obtained by venous sampling. Sample preparation consisted of protein precipitation, evaporation and reconstitution and also included phospholipid filtration for blood and plasma. Moxidectin was detected by multiple reaction monitoring (640.4 → 528.5 m/z) using a Luna C8(2) (30 × 2.0 mm, 3 µm particle size, 100 Å) analytical column with a gradient program of 6 min duration. Validation was performed with respect to accuracy, precision, sensitivity, selectivity, linearity, stability, recovery, and haematocrit influence with a limit of quantification of 0.5 and 2.5 ng/mL, for venous and capillary blood respectively. Moxidectin was stable up to 2 months at storage condition (blood and plasma: -20 °C, microsamples: room temperature), 3 cycles of temperature shift, for at least 4 h on the bench-top and 24 h in the autosampler (4 °C). Deviations of inter- and intra-assay accuracy and precision were smaller than 12.6% and recoveries were in the range of 80.7-111.2%. The method was applied to samples obtained from nine Strongyloides stercoralis-infected adults from northern Laos. A good agreement in the time-concentration profiles of moxidectin and a high consistency in PK parameters was found between the different matrixes and sampling strategies: e.g. identical time to reach maximal concentration of 4.0 h and a similar maximal concentration of 83.9-88.5 ng/mL of moxidectin. The simple and practical capillary procedure using Mitra® microsampling has been demonstrated to be suitable for PK studies of moxidectin and will pave the way for future PK studies.
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http://dx.doi.org/10.1016/j.jchromb.2021.122556DOI Listing
March 2021

Insights gained from conducting a randomised controlled trial on Ivermectin-Albendazole against Trichuris trichiura in Côte d'Ivoire, Lao PDR and Pemba Island.

Adv Parasitol 2021 19;111:253-276. Epub 2020 Dec 19.

Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland. Electronic address:

There is only limited scientific literature on trial methodology, trial procedures and mitigation strategies to overcome challenges faced during clinical research taking place in resource constrained healthcare environments. Organisational, cultural, infrastructural and ethical challenges may vary between settings although conduct of clinical trials for the same disease (in our case soil-transmitted helminth (STH) infections) share similar risks for implementation. We use the example of a phase III randomised controlled trial, conducted between 2018 and 2020 in Côte d'Ivoire, Lao PDR and Pemba Island (Tanzania), to share challenges faced and mitigation strategies to guide future planning of studies in similar settings. We describe the planning, screening, enrolment and implementation phases in each of the three settings. Our findings indicate that involvement of local staff and close collaboration are essential factors for successful trial preparation and implementation. A strategic plan adapted to each setting with a distinct focus on community engagement and workforce is crucial to proceed efficiently. Mutual trust between the trial population and the trial team is of utmost importance and allows for early reaction and adaption to emerging issues.
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http://dx.doi.org/10.1016/bs.apar.2020.11.001DOI Listing
September 2021

Model-based spatial-temporal mapping of opisthorchiasis in endemic countries of Southeast Asia.

Elife 2021 Jan 12;10. Epub 2021 Jan 12.

Department of Medical Statistics, School of Public Health, Sun Yat-sen University, Guangzhou, China.

Opisthorchiasis is an overlooked danger to Southeast Asia. High-resolution disease risk maps are critical but have not been available for Southeast Asia. Georeferenced disease data and potential influencing factor data were collected through a systematic review of literatures and open-access databases, respectively. Bayesian spatial-temporal joint models were developed to analyze both point- and area-level disease data, within a logit regression in combination of potential influencing factors and spatial-temporal random effects. The model-based risk mapping identified areas of low, moderate, and high prevalence across the study region. Even though the overall population-adjusted estimated prevalence presented a trend down, a total of 12.39 million (95% Bayesian credible intervals [BCI]: 10.10-15.06) people were estimated to be infected with in 2018 in four major endemic countries (i.e., Thailand, Laos, Cambodia, and Vietnam), highlighting the public health importance of the disease in the study region. The high-resolution risk maps provide valuable information for spatial targeting of opisthorchiasis control interventions.
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http://dx.doi.org/10.7554/eLife.59755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870142PMC
January 2021

Hepatitis B virus in Lao dentists: A cross-sectional serological study.

Ann Hepatol 2021 May-Jun;22:100282. Epub 2020 Nov 17.

Institut Pasteur du Laos, Vientiane, Lao People's Democratic Republic. Electronic address:

Introduction And Objectives: Hepatitis B virus (HBV) is endemic in Lao PDR, with up to 10% chronic infections in adults. Dentists have high risk of exposure and transmission to their patients. The aim was to investigate the serological profiles of vaccination, exposure and susceptibility to HBV. In addition, we determined the knowledge, attitude and practice (KAP) of Lao dentists toward HBV.

Materials And Methods: Dentists and dental assistants were recruited from 186 private dental clinics in Vientiane Capital. They completed a KAP questionnaire and serum was tested by ELISA for HBV markers (anti-HB surface antigen, anti-core antigen, HBV surface antigen).

Results: 206 dentists and 111 dental workers aged between 18-63 years were included. Serology data showed that 37.8% had previous exposure (49.0% of males and 32.4% of females) and 5.0% were chronically infected (7.7% of males and 3.8% of females). Less than 15% had serological evidence of vaccination and 66.8% were unprotected against infection. Knowledge of HBV was mostly low, for example 61.8% were aware of the childhood HBV vaccine. Just over half said that they should give dental care to HBV carriers. About one quarter reported accidental blood exposure during the last 6 months but knowledge about procedures after exposure was low.

Conclusions: Lao dentists are at high risk of occupational exposure to HBV but have low awareness and serological protection. There is a need to introduce mandatory vaccination, to strengthen occupational health in health care providers and to further develop the academic curricula of dental students.
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http://dx.doi.org/10.1016/j.aohep.2020.10.010DOI Listing
November 2020

An in-depth report of quality control on Kato-Katz and data entry in four clinical trials evaluating the efficacy of albendazole against soil-transmitted helminth infections.

PLoS Negl Trop Dis 2020 09 21;14(9):e0008625. Epub 2020 Sep 21.

Department of Virology, Parasitology and Immunology, Ghent University, Merelbeke, Belgium.

Background: Efforts to control soil-transmitted helminth (STH) infections have intensified over the past decade. Field-survey data on STH prevalence, infection intensity and drug efficacy is necessary to guide the implementation of control programs and should be of the best possible quality.

Methodology: During four clinical trials designed to evaluate the efficacy of albendazole against STHs in Brazil, Ethiopia, Lao PDR and Tanzania, quality control (QC) was performed on the duplicate Kato-Katz thick smears and the data entry. We analyzed datasets following QC on both fecal egg counts (FECs) and data entry, and compared the prevalence of any STH infection and moderate-to-heavy intensity (MHI) infections and the drug efficacy against STH infections.

Results: Across the four study sites, a total of 450 out of 4,830 (9.3%) Kato-Katz thick smears were re-examined. Discrepancies in FECs varied from ~3% (hookworms) to ~6.5% (Ascaris lumbricoides and Trichuris trichiura). The difference in STH prevalence and prevalence of MHI infections using the datasets with and without QC of the FECs did not exceed 0.3%, except for hookworm infections in Tanzania, where we noted a 2.2 percentage point increase in MHI infections (pre-QC: 1.6% vs. post-QC: 3.8%). There was a 100% agreement in the classification of drug efficacy of albendazole against STH between the two datasets. In total, 201 of the 28,980 (0.65%) data entries that were made to digitize the FECs were different between both data-entry clerks. Nevertheless, the overall prevalence of STH, the prevalence of MHI infections and the classification of drug efficacy remained largely unaffected.

Conclusion/significance: In these trials, where staff was informed that QC would take place, minimal changes in study outcomes were reported following QC on FECs or data entry. Nevertheless, imposing QC did reduce the number of errors. Therefore, application of QC together with proper training of the personnel and the availability of clear standard operating procedures is expected to support higher data quality.
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http://dx.doi.org/10.1371/journal.pntd.0008625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549791PMC
September 2020

Cross-reaction of POC-CCA urine test for detection of Schistosoma mekongi in Lao PDR: a cross-sectional study.

Infect Dis Poverty 2020 Aug 12;9(1):114. Epub 2020 Aug 12.

Lao Tropical and Public Health Institute, Ministry of Health, Vientiane Capital, Lao People's Democratic Republic.

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.
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http://dx.doi.org/10.1186/s40249-020-00733-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424653PMC
August 2020

Impact of Different Strategies for Delivering Supplemental Zinc on Selected Fecal Markers of Environmental Enteric Dysfunction among Young Laotian Children: A Randomized Controlled Trial.

Am J Trop Med Hyg 2020 10;103(4):1416-1426

Department of Nutrition, Institute for Global Nutrition, University of California, Davis, Davis, California.

The objective of this study was to assess the impact of different strategies for delivering supplemental zinc on fecal myeloperoxidase (MPO), neopterin (NEO), and calprotectin (CAL) among young Laotian children. In a double-blind controlled trial, children aged 6-23 months were randomized to receive either daily preventive zinc (PZ) tablets (7 mg/day), daily micronutrient powder (MNP; containing 10 mg zinc and 14 other micronutrients), therapeutic zinc (TZ) supplements for diarrhea treatment (20 mg/day for 10 days), or daily placebo powder and followed for ∼36 weeks. Stool samples were collected at baseline and endline. Fecal MPO, NEO, and CAL concentrations were determined in a randomly selected subsample of 720 children using commercially available ELISA kits. At baseline, the mean age was 14.1 ± 4.9 months and prevalence of stunting was 39%. The endline prevalence of stunting was 43%; there was no overall treatment effect on physical growth in the parent trial. At endline, the mean (95% CI) MPO in the PZ group was 1,590 [1,396; 1,811] ng/mL and did not differ from that in the MNP (1,633 [1,434; 1,859] ng/mL), TZ (1,749 [1,535; 1,992] ng/mL), and control (1,612 [1,415; 1,836] ng/mL) groups ( = 0.749). Similarly, there was no overall treatment effect on NEO and CAL concentrations ( = 0.226 and 0.229, respectively). In this population, the provision of PZ or TZ supplements or MNP had no impact on growth or environmental enteric dysfunction (EED) as assessed by fecal MPO, NEO, and CAL. Additional research is needed to better understand the etiology and proposed mechanisms of EED pathogenesis.
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http://dx.doi.org/10.4269/ajtmh.20-0106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543857PMC
October 2020

Identifying thresholds for classifying moderate-to-heavy soil-transmitted helminth intensity infections for FECPAKG2, McMaster, Mini-FLOTAC and qPCR.

PLoS Negl Trop Dis 2020 07 2;14(7):e0008296. Epub 2020 Jul 2.

Department of Parasitology, National Institute of Malariology, Parasitology and Entomology, Ha Noi, Vietnam.

The World Health Organization (WHO) has defined moderate-to-heavy intensity (M&HI) infections with soil-transmitted helminths (Ascaris lumbricoides, Trichuris trichiura and the two hookworms, Ancylostoma duodenale and Necator americanus) based on specific values of eggs per gram of stool, as measured by the Kato-Katz method. There are a variety of novel microscopy and DNA-based methods but it remains unclear whether applying current WHO thresholds on to these methods allows for a reliable classification of M&HI infections. We evaluated both WHO and method-specific thresholds for classifying the M&HI infections for novel microscopic (FECPAKG2, McMaster and Mini-FLOTAC) and DNA-based (qPCR) diagnostic methods. For this, we determined method-specific thresholds that best classified M&HI infections (defined by Kato-Katz and WHO thresholds; reference method) in two multi-country drug efficacy studies. Subsequently, we verified whether applying these method-specific thresholds improved the agreement in classifying M&HI infections compared to the reference method. When we applied the WHO thresholds, the new microscopic methods mainly misclassified M&HI as low intensity, and to a lesser extent low intensity infection as M&HI. For FECPAKG2, applying the method-specific thresholds significantly improved the agreement for Ascaris (moderate → substantial), Trichuris and hookworms (fair → moderate). For Mini-FLOTAC, a significantly improved agreement was observed for hookworms only (fair → moderate). For the other STHs, the agreement was almost perfect and remained unchanged. For McMaster, the method-specific thresholds revealed a fair to a substantial agreement but did not significantly improve the agreement. For qPCR, the method-specific thresholds based on genome equivalents per ml of DNA moderately agreed with the reference method for hookworm and Trichuris infections. For Ascaris, there was a substantial agreement. We defined method-specific thresholds that improved the classification of M&HI infections. Validation studies are required before they can be recommended for general use in assessing M&HI infections in programmatic settings.
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http://dx.doi.org/10.1371/journal.pntd.0008296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413557PMC
July 2020

One mean to rule them all? The arithmetic mean based egg reduction rate can be misleading when estimating anthelminthic drug efficacy in clinical trials.

PLoS Negl Trop Dis 2020 04 8;14(4):e0008185. Epub 2020 Apr 8.

University of Basel, Basel, Switzerland.

Animal and human helminth infections are highly prevalent around the world, with only few anthelminthic drugs available. The anthelminthic drug performance is expressed by the cure rate and the egg reduction rate. However, which kind of mean should be used to calculate the egg reduction rate remains a controversial issue. We visualized the distributions of egg counts of different helminth species in 7 randomized controlled trials and asked a panel of experts about their opinion on the egg burden and drug efficacy of two different treatments. Simultaneously, we calculated infection intensities and egg reduction rates using different types of means: arithmetic, geometric, trimmed, winsorized and Hölder means. Finally, we calculated the agreement between expert opinion and the different means. We generated 23 different trial arm pairs, which were judged by 49 experts. Among all investigated means, the arithmetic mean showed poorest performance with only 64% agreement with expert opinion (bootstrap confidence interval [CI]: 60-68). Highest agreement of 94% (CI: 86-96) was reached by the Hölder mean M0.2, followed by the geometric mean (91%, CI: 85-94). Winsorized and trimmed means showed a rather poor performance (e.g. winsorization with 0.1 cut-off showed 85% agreement, CI: 78-87), but they performed reasonably well after excluding treatment arms with a small number of patients. In clinical trials with moderate sample size, the currently recommended arithmetic mean does not necessarily rank anthelminthic efficacies in the same order as might be obtained from expert evaluation of the same data. Estimates based on the arithmetic mean should always be reported together with an estimate, which is more robust to outliers, e.g. the geometric mean.
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http://dx.doi.org/10.1371/journal.pntd.0008185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170292PMC
April 2020

Lasting benefit of infant hepatitis B vaccination in adolescents in the Lao People's Democratic Republic.

Int J Infect Dis 2020 Apr 31;93:217-223. Epub 2020 Jan 31.

Lao-Lux Laboratory, Institut Pasteur du Laos, Vientiane, Lao Democratic People's Republic.

Objectives: Hepatitis B is endemic in Lao PDR with 8-10% of the adult population being chronically infected. We investigated the impact of hepatitis B vaccination on infection in adolescents born shortly before and after the introduction of the vaccine in 2001.

Methods: 779 students from Vientiane Capital and Bolikhamxay province were tested for HBV markers by ELISA. Socio-demographic information was collected with a standardized questionnaire. Predictors/risk factors for seroprotection or exposure to hepatitis B infection were assessed by bivariate and multivariable analyses.

Results: The prevalence of a serological vaccination profile increased significantly after the introduction of the vaccine (13.2%-21.9%, p < 0.05, in Vientiane; 3.0%-19.7%, p < 0.001, in Bolikhamxay), which translated into at least a 2-times lower prevalence of past infection. In logistic regression, older students in Bolikhamxay were less likely to be vaccinated and more likely to have been infected by HBV in the past.

Conclusion: Even though this study documented a sizable and lasting reduction in past hepatitis B infections in adolescents born after the introduction of infant hepatitis B vaccination, the overall levels of protective anti-HBs were low and warrant at least the introduction of a booster for adolescents. Furthermore, we suggest improving the coverage of the hepatitis B birth dose.
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http://dx.doi.org/10.1016/j.ijid.2020.01.055DOI Listing
April 2020

AuNPs-LISA, an efficient detection assay for Opisthorchis viverrini (Ov) antigen in urine.

Talanta 2020 Mar 27;209:120592. Epub 2019 Nov 27.

Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Khon Kaen University, Khon Kaen, Thailand. Electronic address:

The enzyme-linked immunosorbent assay (ELISA) is currently a powerful technique for the detection of Opisthorchis viverrini antigen (OvAg) in urine samples. However, its sensitivity and analysis time need to be improved. In the present study, we aimed to improve the signal enhancing system of traditional ELISA by using gold nanoparticles (AuNPs) with peroxidase-like activity on its surface instead of the horseradish peroxidase (HRP) system. The catalytic activity of the AuNPs probe can be boosted by the gold enhancing solution and the addition of ATP. The catalytic ability of the AuNPs probe depended on the probe and the HO concentration. The proposed approach can reduce the number of the traditional ELISA steps with better detection sensitivity. Interestingly, the limit of detection (LOD) of the test was 23.4 ng mL, substantially lower than the 93.8 ng mL for the traditional ELISA. The AuNPs-LISA assay showed higher sensitivity and specificity, 93.81% and 91.34%, respectively, compared to the traditional ELISA. The proposed assay was successfully applied for the detection of OvAg in urine samples. This will provide an effective tool for the detection, control and elimination of human opisthorchiasis.
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http://dx.doi.org/10.1016/j.talanta.2019.120592DOI Listing
March 2020

Patients with severe schistosomiasis mekongi morbidity demonstrating ongoing transmission in Southern Lao People's Democratic Republic.

Acta Trop 2020 Apr 28;204:105323. Epub 2019 Dec 28.

Swiss Tropical and Public Health Institute, Basel CH-4002, Switzerland; University of Basel, Basel, Switzerland. Electronic address:

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.
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http://dx.doi.org/10.1016/j.actatropica.2019.105323DOI Listing
April 2020

Morbidity associated with Schistosoma mekongi and concurrent helminth infection in Lao People's Democratic Republic.

Acta Trop 2020 Apr 28;204:105324. Epub 2019 Dec 28.

Swiss Tropical and Public Health Institute, P.O. Box, CH-4002 Basel, Switzerland; University of Basel, P.O. Box, CH-4003 Basel, Switzerland. Electronic address:

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.
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http://dx.doi.org/10.1016/j.actatropica.2019.105324DOI Listing
April 2020

High prevalence of helminth infections in mother-child pairs from three central provinces of Lao People's Democratic Republic.

Parasite Epidemiol Control 2019 Nov 2;7:e00122. Epub 2019 Nov 2.

Lao-Lux-Laboratory, Institute Pasteur Du Laos, Vientiane, Lao Democratic People's Republic.

In Southeast Asia, the large majority of the population remains affected by parasitic worms despite longstanding mass treatment and health education campaigns. Soil-transmitted helminths and also the fish-borne liver fluke negatively affect development during early childhood. Here, the prevalence of helminth infections in stool samples of 610 mother-child pairs from Khammouane, Bolikhamxay and Vientiane provinces in Lao People's Democratic Republic was determined by formalin-ethyl acetate concentration technique. Overall, 15.1% of the children and 46.9% of the mothers were positive for at least one helminth species. Helminth detection rates varied significantly by province with the highest prevelance in Khammouane and the lowest in Bolikhamxay province. Mothers that were positive for soil-transmitted helminths were significantly more likely to have children positive for the same helminth species (p < 0.01) but this was not the case for the liver fluke A protective effect of breastfeeding against soil-transmitted helminths was revealed. Our data reconfirm the generally high helminth burden among mother-child pairs who likely share a number of risky lifestyle behaviors also with other family members. To reduce maternal burden of helminths, we propose that anti-helmintic treatment of women of childbearing age and of mothers during postnatal care should be included in the national strategy.
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http://dx.doi.org/10.1016/j.parepi.2019.e00122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6911889PMC
November 2019

Impact of Different Sampling Schemes for Decision Making in Soil-Transmitted Helminthiasis Control Programs.

J Infect Dis 2020 06;221(Suppl 5):S531-S538

Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Starting and stopping preventive chemotherapy (PC) for soil-transmitted helminthiasis is typically based on the prevalence of infection as measured by Kato-Katz (KK) fecal smears. Kato-Katz-based egg counts can vary highly over repeated stool samples and smears. Consequentially, the sensitivity of KK-based surveys depends on the number of stool samples per person and the number of smears per sample. Given finite resources, collecting multiple samples and/or smears means screening fewer individuals, thereby lowering the statistical precision of prevalence estimates. Using population-level data from various epidemiological settings, we assessed the performance of different sampling schemes executed within the confines of the same budget. We recommend the use of single-slide KK for determining prevalence of moderate-to-heavy intensity infection and policy decisions for starting and continuing PC; more sensitive sampling schemes may be required for policy decisions involving stopping PC. Our findings highlight that guidelines should include specific guidance on sampling schemes.
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http://dx.doi.org/10.1093/infdis/jiz535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289558PMC
June 2020

Multi-disciplinary integration of networking through the RNAS: Research on other target diseases.

Adv Parasitol 2019 19;105:95-110. Epub 2019 Aug 19.

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, China; Chinese Center for Tropical Diseases Research, Shanghai, China; WHO Collaborating Centre for Tropical Diseases, Shanghai, China; National Center for International Research on Tropical Diseases, Shanghai, China; Key Laboratory of Parasite and Vector Biology, Ministry of Health, Shanghai, China.

In 2005, the network decided to increase its number of target diseases to include other helminthic zoonoses such as fascioliasis, clonorchiasis, opisthorchiasis, paragonimiasis and cysticercosis and in the process expanding membership to include South Korea, Vietnam, Thailand and Japan. NTDs were eventually included as awareness is heightened on these diseases affecting poor and developing countries. Researches on clonorchiasis and opisthorchiasis unravel the mechanism by which these diseases eventually predispose to cholangiocarcinoma. The liver cancer associated with these liver fluke infections necessitate the need to clarify the global burden of disease of these infections. The magnitude of these liver fluke diseases in endemic countries like China, Vietnam, Laos, Cambodia and Thailand is described. Success in elimination of lymphatic filariasis in PR China and Cambodia is highlighted to show how intensified multisectoral collaboration and strong political become strong ingredients in elimination of parasitic diseases like LF. New advances are presented that clarify species and strain differences in Fasciola spp., Paragonimus spp., Taenia spp. and Echinococcocus spp. Conventional diagnostic techniques are compared with new serologic techniques that are being developed. New control strategies such as the Lawa model are presented.
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http://dx.doi.org/10.1016/bs.apar.2019.07.010DOI Listing
January 2020

From country control programmes to translational research.

Adv Parasitol 2019 6;105:69-93. Epub 2019 Sep 6.

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention; Chinese Center for Tropical Diseases Research; WHO Collaborating Centre for Tropical Diseases, China; National Center for International Research on Tropical Diseases, China; Key Laboratory of Parasite and Vector Biology, Ministry of Health, China, Shanghai, China. Electronic address:

From the time it was conceptualized in 1998 to the present, RNAS has largely concentrated on research that will generate results to facilitate control, prevention and elimination of its target diseases. Diagnostics has remained an active field of research in order to develop tools that are appropriate for each stage from the first efforts until attempts to block transmission. For example, with regard to schistosomiasis, chemotherapy has excellent impact on morbidity, while better diagnostics and vaccine research have been promoted to complement the other components of the control programme. The need for surveillance in areas where the prevalence has been brought down to very low levels necessitated development of spatio-temporal tools and ecological models based on geographical information systems (GIS) to produce risk and distribution maps for monitoring and evaluation of programme success. New knowledge and experiences in management of the diseases contribute to the formulation of new schemes in management and treatment. Ways of drawing attention to the disease, such as determining disability weights for use in computation of burden of disease, updating epidemiological profile and unravelling new aspects of the disease provide bases for modifying the operation of control programmes as we move forward. Programme evaluation based on reports of actual implementation of activities brought to the fore problems related to the distribution of chemotherapy as well as social, cultural and behavioural aspects of endemic communities. Importantly, this highlighted the necessity of adapting control activities to specific situations of the endemic areas. New models evolving from reviews of this kind and success stories, such us the elimination of lymphatic filariasis (LF) in PR China and Cambodia are presented.
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http://dx.doi.org/10.1016/bs.apar.2019.07.005DOI Listing
January 2020

Collaborative RNAS research: Priorities and outcomes.

Adv Parasitol 2019 19;105:23-52. Epub 2019 Aug 19.

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, China; Chinese Center for Tropical Diseases Research, Shanghai, China; WHO Collaborating Centre for Tropical Diseases, Shanghai, China; National Center for International Research on Tropical Diseases, Shanghai, China; Key Laboratory of Parasite and Vector Biology, Ministry of Health, Shanghai, China.

Over the past 20 years, RNAS has been generating research results from highly collaborative projects meant to promote and advance understanding in various aspects of schistosomiasis. Epidemiological studies in endemic countries like the Philippines, the People's Republic of China (PR China), the Lao People's Democratic Republic (Lao PDR) and Cambodia clarified the role of reservoir hosts in transmission and the use of spatio-temporal methods such as remote sensing and geographical information systems (GIS) in surveillance of schistosomiasis. Morbidity studies proposed factors that might influence development of fibrosis, anaemia and malnutrition in schistosomiasis. Immune responses in schistosomiasis continue to be an interesting focus in research to explain possible development of resistance with age. Results of evaluation of candidate vaccine molecules are also presented. New diagnostics are continually being developed in response to the call for more sensitive and field applicable techniques that will be used for surveillance in areas nearing elimination of the disease. Several studies presented here show the insufficiency of mass drug administration (MDA) with praziquantel in eliminating the disease. Emphasis is given to an integrated control approach that can be accomplished through intensive and extensive intersectoral collaboration.
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http://dx.doi.org/10.1016/bs.apar.2019.07.007DOI Listing
January 2020

Therapeutic efficacy of albendazole against soil-transmitted helminthiasis in children measured by five diagnostic methods.

PLoS Negl Trop Dis 2019 08 1;13(8):e0007471. Epub 2019 Aug 1.

Department of Virology, Parasitology and Immunology, Ghent University, Merelbeke, Belgium.

Background: Preventive chemotherapy (PC) with benzimidazole drugs is the backbone of soil-transmitted helminth (STH) control programs. Over the past decade, drug coverage has increased and with it, the possibility of developing anthelmintic resistance. It is therefore of utmost importance to monitor drug efficacy. Currently, a variety of novel diagnostic methods are available, but it remains unclear whether they can be used to monitor drug efficacy. In this study, we compared the efficacy of albendazole (ALB) measured by different diagnostic methods in a head-to-head comparison to the recommended single Kato-Katz.

Methods: An ALB efficacy trial was performed in 3 different STH-endemic countries (Ethiopia, Lao PDR and Tanzania), each with a different PC-history. During these trials, stool samples were evaluated with Kato-Katz (single and duplicate), Mini-FLOTAC, FECPAKG2, and qPCR. The reduction rate in mean eggs per gram of stool (ERR) and mean genome equivalents / ml of DNA extract (GERR) were calculated to estimate drug efficacy.

Principal Findings And Conclusions: The results of the efficacy trials showed that none of the evaluated diagnostic methods could provide reduction rates that were equivalent to a single Kato-Katz for all STH. However, despite differences in clinical sensitivity and egg counts, they agreed in classifying efficacy according to World Health Organization (WHO) guidelines. This demonstrates that diagnostic methods for assessing drug efficacy should be validated with their intended-use in mind and that other factors like user-friendliness and costs will likely be important factors in driving the choice of diagnostics. In addition, ALB efficacy against STH infections was lower in sites with a longer history of PC. Yet, further research is needed to identify factors that contribute to this finding and to verify whether reduced efficacy can be associated with mutations in the β-tubulin gene that have previously been linked to anthelmintic resistance.

Trial Registration: ClinicalTrials.gov NCT03465488.
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http://dx.doi.org/10.1371/journal.pntd.0007471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6675043PMC
August 2019

Diagnostic performance of a single and duplicate Kato-Katz, Mini-FLOTAC, FECPAKG2 and qPCR for the detection and quantification of soil-transmitted helminths in three endemic countries.

PLoS Negl Trop Dis 2019 08 1;13(8):e0007446. Epub 2019 Aug 1.

Department of Virology, Parasitology and Immunology, Ghent University, Merelbeke, Belgium.

Background: Because the success of deworming programs targeting soil-transmitted helminths (STHs) is evaluated through the periodically assessment of prevalence and infection intensities, the use of the correct diagnostic method is of utmost importance. The STH community has recently published for each phase of a deworming program the minimal criteria that a potential diagnostic method needs to meet, the so-called target product profiles (TPPs).

Methodology: We compared the diagnostic performance of a single Kato-Katz (reference method) with that of other microscopy-based methods (duplicate Kato-Katz, Mini-FLOTAC and FECPAKG2) and one DNA-based method (qPCR) for the detection and quantification of STH infections in three drug efficacy trials in Ethiopia, Lao PDR, and Tanzania. Furthermore, we evaluated a selection of minimal diagnostic criteria of the TPPs.

Principal Findings: All diagnostic methods showed a clinical sensitivity of ≥90% for all STH infections of moderate-to-heavy intensities. For infections of very low intensity, only qPCR resulted in a sensitivity that was superior to a single Kato-Katz for all STHs. Compared to the reference method, both Mini-FLOTAC and FECPAKG2 resulted in significantly lower fecal egg counts for some STHs, leading to a substantial underestimation of the infection intensity. For qPCR, there was a positive significant correlation between the egg counts of a single Kato-Katz and the DNA concentration.

Conclusions/significance: Our results indicate that the diagnostic performance of a single Kato-Katz is underestimated by the community and that diagnostic specific thresholds to classify intensity of infection are warranted for Mini-FLOTAC, FECPAKG2 and qPCR. When we strictly apply the TPPs, Kato-Katz is the only microscopy-based method that meets the minimal diagnostic criteria for application in the planning, monitoring and evaluation phase of an STH program. qPCR is the only method that could be considered in the phase that aims to seek confirmation for cessation of program.

Trial Registration: ClinicalTrials.gov NCT03465488.
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http://dx.doi.org/10.1371/journal.pntd.0007446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6675048PMC
August 2019

Efficacy and safety of ivermectin and albendazole co-administration in school-aged children and adults infected with Trichuris trichiura: study protocol for a multi-country randomized controlled double-blind trial.

BMC Infect Dis 2019 Mar 18;19(1):262. Epub 2019 Mar 18.

Swiss Tropical and Public Health Institute, Basel, Switzerland.

Background: Soil-transmitted helminthiasis affects almost 2 billion people worldwide in tropical climates. Preventive chemotherapy, using the benzimidazoles (albendazole and mebendazole) is the current main recommended control strategy. Nevertheless, there is limited efficacy of these drugs against hookworm infection and, to a greater extent, against trichuriasis. We describe a protocol for a trial investigating the efficacy and safety of the co-administration of ivermectin and albendazole against trichuriasis.

Methods: A double-blind, placebo-controlled randomized controlled trial will be conducted in three countries (Côte d'Ivoire, Tanzania and Lao PDR) with the aim to determine the efficacy, safety and extended effects of co-administered ivermectin and albendazole compared to standard albendazole monotherapy. We will enroll 600 participants aged 6-60 years in each setting. The primary outcome is cure rate (CR) against Trichuris trichiura infection as assessed by Kato-Katz 14-21 days after treatment. Secondary outcomes include CRs against concomitant soil-transmitted helminth (STH) infections (Ascaris lumbricoides, hookworm and Strongyloides stercoralis) and egg reduction rates (ERRs) against STH at 14-21 days, 180 days and 360 days. Tolerability of treatment, infection status assessed by polymerase chain reaction (PCR), and potential benefits of deworming on nutritional and morbidity indicators will be assessed. The primary analysis will include an available-case set and use logistic regression models adjusted for age, sex and weight.

Discussion: This trial will provide robust results on the efficacy and safety of co-administration of ivermectin and albendazole with the aim to better inform WHO recommendations on control of STHs. Furthermore, secondary and explanatory outcomes will provide direct evidence on the extended effects of combination therapy and insight on the relationship between nutrition and morbidity parameters and infection status and intensity.

Trial Registration: NCT03527732 (date assigned: 17 May 2018).
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Source
http://dx.doi.org/10.1186/s12879-019-3882-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421712PMC
March 2019
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