Publications (60)537.29 Total impact
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Article: Effect of High-Dose or Split-Dose Artesunate on Parasite Clearance in Artemisinin-Resistant Falciparum Malaria
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ABSTRACT: Background. The emergence of Plasmodium falciparum resistance to artemisinins on the Cambodian and Myanmar-Thai borders poses severe threats to malaria control. We investigated whether increasing or splitting the dose of the short half-life drug artesunate improves parasite clearance in falciparum malaria in the two regions.Methods. In Pailin, Western Cambodia (from 2008 to 2010) and Wang Pha, North-western Thailand (2009-2010), patients with uncomplicated falciparum malaria were randomized to oral artesunate 6 mg/kg/day as single or twice-daily dose for 7 days, or artesunate 8 mg/kg/day as single or twice daily dose for 3 days, followed by mefloquine. Parasite clearance and recrudescence up to 63-days follow-up were assessed. Trial registration: ISRCTN15351875.Results. A total of 159 patients were enrolled. Overall median (IQR) parasitaemia half-life (half-life) was 6.03 (4.89-7.28) hours in Pailin versus 3.42 (2.20-4.85) hours in Wang Pha (p=0.0001). Splitting or increasing the artesunate dose did not shorten half-life in either site. Pharmacokinetic profiles of artesunate and dihydroartemisinin were similar between sites and did not correlate with half-life. Recrudescent infections occurred in 4 out of 79 patients in Pailin and 5/80 in Wang Pha and was not different between treatment arms (p=0.68). High dose artesunate was associated with transient reticulocytopenia and in one patient with transient neutropenia (0.78 x 10(3)/μL) at day 14.Conclusions. Increasing the artesunate treatment dose up to 8 mg/kg/day or splitting the dose does not improve parasite clearance in either artemisinin resistant or more sensitive infections with P. falciparum.Clinical Infectious Diseases 03/2013; 56(5):e48-e58. · 9.15 Impact Factor -
Article: Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in Southeast Asia.
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ABSTRACT: The recent emergence of artemisinin-resistant Plasmodium falciparum malaria in western Cambodia could threaten prospects for malaria elimination. Identification of the genetic basis of resistance would provide tools for molecular surveillance, aiding efforts to contain resistance. Clinical trials of artesunate efficacy were conducted in Bangladesh, in northwestern Thailand near the Myanmar border, and at two sites in western Cambodia. Parasites collected from trial participants were genotyped at 8,079 single nucleotide polymorphisms (SNPs) using a P. falciparum-specific SNP array. Parasite genotypes were examined for signatures of recent positive selection and association with parasite clearance phenotypes to identify regions of the genome associated with artemisinin resistance. Four SNPs on chromosomes 10 (one), 13 (two), and 14 (one) were significantly associated with delayed parasite clearance. The two SNPs on chromosome 13 are in a region of the genome that appears to be under strong recent positive selection in Cambodia. The SNPs on chromosomes 10 and 13 lie in or near genes involved in postreplication repair, a DNA damage-tolerance pathway. Replication and validation studies are needed to refine the location of loci responsible for artemisinin resistance and to understand the mechanism behind it; however, two SNPs on chromosomes 10 and 13 may be useful markers of delayed parasite clearance in surveillance for artemisinin resistance in Southeast Asia.Proceedings of the National Academy of Sciences 12/2012; · 9.68 Impact Factor -
Article: Optimizing the HRP-2 in vitro malaria drug susceptibility assay using a reference clone to improve comparisons of Plasmodium falciparum field isolates.
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ABSTRACT: BACKGROUND: Apparent emerging artemisinin-resistant Plasmodium falciparum malaria in Southeast Asia requires development of practical tools to monitor for resistant parasites. Although in vitro anti-malarial susceptibility tests are widely used, uncertainties remain regarding interpretation of P. falciparum field isolate values. METHODS: Performance parameters of the W2 P. falciparum clone (considered artemisinin "sensitive") were evaluated as a reference for the HRP-2 immediate ex vivo assay. Variability in W2 IC50s was assessed, including intra- and inter-assay variability among and between technicians in multiple experiments, over five freeze-thaw cycles, over five months of continuous culture, and before and after transport of drug-coated plates to remote field sites. Nominal drug plate concentrations of artesunate (AS) and dihydroartemisinin (DHA) were verified by LC-MS analysis. Plasmodium falciparum field isolate IC50s for DHA from subjects in an artemisininresistant area in Cambodia were compared with W2 susceptibility. RESULTS: Plate drug concentrations and day-to-day technical assay performance among technicians were important sources of variability for W2 IC50s within and between assays. Freeze-thaw cycles, long-term continuous culture, and transport to and from remote sites had less influence. Despite variability in W2 susceptibility, the median IC50s for DHA for Cambodian field isolates were higher (p <0.0001) than the W2 clone (3.9 nM), both for subjects with expected (less than 72 hours; 6.3 nM) and prolonged (greater or equal to 72 hours; 9.6 nM) parasite clearance times during treatment with artesunate monotherapy. CONCLUSION: The W2 reference clone improved the interpretability of field isolate susceptibility from the immediate ex vivo HRP-2 assay from areas of artemisinin resistance. Methods to increase the reproducibility of plate coating may improve overall assay interpretability and utility.Malaria Journal 09/2012; 11(1):325. · 3.19 Impact Factor -
Article: Prevalence of Opisthorchis viverrini infection in humans and fish in Kratie Province, Cambodia.
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ABSTRACT: Opisthorchis viverrini is a medically important foodborne parasite in the Indochina Peninsula. In Cambodia, the prevalence of this trematode has been reported in Takeo Province, but not in other areas. In this study, we investigated the prevalence of O. viverrini infection among people in seven riparian villages along the Mekong River, Kratie Province. We also examined the status of metacercarial infection in fish hosts. Fecal specimens were collected from 2101 residents and schoolchildren, and were examined by the Kato-Katz technique. The average O. viverrini egg positive rate was 4.6%, with the highest prevalence found in Roka Kandal A village (10.4%) followed by Talous village (5.9%). In these villages, adult residents showed higher prevalences (19.4% and 9.0%, respectively) than schoolchildren (6.4% and 1.4%, respectively). O. viverrini adult worms were recovered from 2 egg-positive cases (18 and 4 specimens) after praziquantel treatment and purgation. In addition, three of seven freshwater fish species caught near the villages were positive for O. viverrini metacercariae. A total of 367 metacercariae were harvested from 19 infected fish (metacercarial density; 19 per fish). The species of the metacercariae was confirmed through adult worm recovery by experimental infection to hamsters. The results provide evidence that the surveyed areas of Kratie Province, Cambodia, are endemic for O. viverrini infection.Acta tropica 08/2012; 124(3):215-20. · 2.22 Impact Factor -
Article: Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing.
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ABSTRACT: Malaria elimination strategies require surveillance of the parasite population for genetic changes that demand a public health response, such as new forms of drug resistance. Here we describe methods for the large-scale analysis of genetic variation in Plasmodium falciparum by deep sequencing of parasite DNA obtained from the blood of patients with malaria, either directly or after short-term culture. Analysis of 86,158 exonic single nucleotide polymorphisms that passed genotyping quality control in 227 samples from Africa, Asia and Oceania provides genome-wide estimates of allele frequency distribution, population structure and linkage disequilibrium. By comparing the genetic diversity of individual infections with that of the local parasite population, we derive a metric of within-host diversity that is related to the level of inbreeding in the population. An open-access web application has been established for the exploration of regional differences in allele frequency and of highly differentiated loci in the P. falciparum genome.Nature 06/2012; 487(7407):375-9. · 36.28 Impact Factor -
Article: High prevalence of Opisthorchis viverrini infection in a riparian population in Takeo Province, Cambodia.
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ABSTRACT: Opisthorchis viverrini infection was found to be highly prevalent in 3 riverside villages (Ang Svay Chek A, B, and C) of the Prey Kabas District, Takeo Province. This area is located in the southern part of Cambodia, where the recovery of adult O. viverrini worms was recently reported. From May 2006 until May 2010, fecal examinations were performed on a total of 1,799 villagers using the Kato-Katz thick smear technique. In the 3 villages, the overall positive rate for helminth eggs ranged from 51.7 to 59.0% (av. 57.4%), and the percentage positive for O. viverrini was 46.4-50.6% (47.5%). Other helminths detected included hookworms (13.2%), echinostomes (2.9%), Trichuris trichiura (1.3%), Ascaris lumbricoides (0.6%), and Taenia spp. (0.06%). The prevalence of O. viverrini eggs appeared to reflect a lower infection in younger individuals (<20 years) than in the adult population (>20 years). Men (50.4%) revealed a significantly higher (P=0.02) prevalence than women (44.3%). The Ang Svay Chek villages of the Prey Kabas District, Takeo Province, Cambodia have been confirmed to be a highly endemic area for human O. viverrini infection.The Korean Journal of Parasitology 06/2012; 50(2):173-6. · 1.04 Impact Factor -
Article: Scale-up of community-based malaria control can be achieved without degrading community health workers' service quality: the Village Malaria Worker project in Cambodia.
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ABSTRACT: Malaria control has been scaled up in many developing countries in their efforts to achieve the Millennium Development Goals. Cambodia recently scaled up their Village Malaria Worker (VMW) project by substantially increasing the number of VMWs and expanding the project's health services to include treatment of fever, diarrhoea, and Acute Respiratory Infections (ARI) in children under five. This study examined if the scale-up interfered with VMWs' service quality, actions, and knowledge of malaria control, and analysed VMWs' overall achievements and perceptions of the newly added health services. Structured interviews were conducted pre scale-up in February-March 2008 with 251 VMWs and post scale-up in July-August 2010 with 252 VMWs. Comparing the pre and post scale-up survey results (n = 195), changes were examined in terms of VMWs' 1) service quality, 2) malaria prevention and vector control actions, and 3) knowledge of malaria epidemiology and vector ecology. In addition, VMWs' newly added health services were descriptively analysed based on the post scale-up survey (n = 252). VMWs' service quality and actions significantly improved overall during the scale-up of the VMW project (mean index score: +0.805, p < 0.001; +2.923, p < 0.001; respectively). Although most of knowledge areas also showed significant improvement (between +0.256 and +0.499, p < 0.001), less than half (10.3%-47.7%) of the VMWs correctly answered a set of questions on malaria epidemiology and vector ecology, even in the post scale-up survey. About 70% of the respondents reported that their health services to control malaria remained the same or that they were more active after the scale-up. Two-thirds (66.3%) had become more enthusiastic about serving as a VMW since the scale-up, and all but one respondent reported being willing to continue the new services. The Cambodian experience clearly demonstrated that a nationwide scale-up of community-based malaria control can be achieved without degrading community health workers' service quality. The government's strategy to expand VMWs' health services, while providing sufficient training to maintain the quality of their original malaria control services, could have contributed to the improvement of VMW's service quality, actions, and knowledge in spite of the rapid scale-up of the project.Malaria Journal 01/2012; 11:4. · 3.19 Impact Factor -
Article: Optimising strategies for Plasmodium falciparum malaria elimination in Cambodia: primaquine, mass drug administration and artemisinin resistance.
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ABSTRACT: Malaria elimination requires a variety of approaches individually optimized for different transmission settings. A recent field study in an area of low seasonal transmission in South West Cambodia demonstrated dramatic reductions in malaria parasite prevalence following both mass drug administration (MDA) and high treatment coverage of symptomatic patients with artemisinin-piperaquine plus primaquine. This study employed multiple combined strategies and it was unclear what contribution each made to the reductions in malaria. A mathematical model fitted to the trial results was used to assess the effects of the various components of these interventions, design optimal elimination strategies, and explore their interactions with artemisinin resistance, which has recently been discovered in Western Cambodia. The modelling indicated that most of the initial reduction of P. falciparum malaria resulted from MDA with artemisinin-piperaquine. The subsequent continued decline and near elimination resulted mainly from high coverage with artemisinin-piperaquine treatment. Both these strategies were more effective with the addition of primaquine. MDA with artemisinin combination therapy (ACT) increased the proportion of artemisinin resistant infections, although much less than treatment of symptomatic cases with ACT, and this increase was slowed by adding primaquine. Artemisinin resistance reduced the effectiveness of interventions using ACT when the prevalence of resistance was very high. The main results were robust to assumptions about primaquine action, and immunity. The key messages of these modelling results for policy makers were: high coverage with ACT treatment can produce a long-term reduction in malaria whereas the impact of MDA is generally only short-term; primaquine enhances the effect of ACT in eliminating malaria and reduces the increase in proportion of artemisinin resistant infections; parasite prevalence is a better surveillance measure for elimination programmes than numbers of symptomatic cases; combinations of interventions are most effective and sustained efforts are crucial for successful elimination.PLoS ONE 01/2012; 7(5):e37166. · 4.09 Impact Factor -
Article: Using CF11 cellulose columns to inexpensively and effectively remove human DNA from Plasmodium falciparum-infected whole blood samples.
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ABSTRACT: Genome and transcriptome studies of Plasmodium nucleic acids obtained from parasitized whole blood are greatly improved by depletion of human DNA or enrichment of parasite DNA prior to next-generation sequencing and microarray hybridization. The most effective method currently used is a two-step procedure to deplete leukocytes: centrifugation using density gradient media followed by filtration through expensive, commercially available columns. This method is not easily implemented in field studies that collect hundreds of samples and simultaneously process samples for multiple laboratory analyses. Inexpensive syringes, hand-packed with CF11 cellulose powder, were recently shown to improve ex vivo cultivation of Plasmodium vivax obtained from parasitized whole blood. This study was undertaken to determine whether CF11 columns could be adapted to isolate Plasmodium falciparum DNA from parasitized whole blood and achieve current quantity and purity requirements for Illumina sequencing. The CF11 procedure was compared with the current two-step standard of leukocyte depletion using parasitized red blood cells cultured in vitro and parasitized blood obtained ex vivo from Cambodian patients with malaria. Procedural variations in centrifugation and column size were tested, along with a range of blood volumes and parasite densities. CF11 filtration reliably produces 500 nanograms of DNA with less than 50% human DNA contamination, which is comparable to that obtained by the two-step method and falls within the current quality control requirements for Illumina sequencing. In addition, a centrifuge-free version of the CF11 filtration method to isolate P. falciparum DNA at remote and minimally equipped field sites in malaria-endemic areas was validated. CF11 filtration is a cost-effective, scalable, one-step approach to remove human DNA from P. falciparum-infected whole blood samples.Malaria Journal 01/2012; 11:41. · 3.19 Impact Factor -
Article: Socially-marketed rapid diagnostic tests and ACT in the private sector: ten years of experience in Cambodia.
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ABSTRACT: Whilst some populations have recently experienced dramatic declines in malaria, the majority of those most at risk of Plasmodium falciparum malaria still lack access to effective treatment with artemisinin combination therapy (ACT) and others are already facing parasites resistant to artemisinins.In this context, there is a crucial need to improve both access to and targeting of ACT through greater availability of good quality ACT and parasitological diagnosis. This is an issue of increasing urgency notably in the private commercial sector, which, in many countries, plays an important role in the provision of malaria treatment. The Affordable Medicines Facility for malaria (AMFm) is a recent initiative that aims to increase the provision of affordable ACT in public, private and NGO sectors through a manufacturer-level subsidy. However, to date, there is little documented experience in the programmatic implementation of subsidized ACT in the private sector. Cambodia is in the unique position of having more than 10 years of experience not only in implementing subsidized ACT, but also rapid diagnostic tests (RDT) as part of a nationwide social marketing programme. The programme includes behaviour change communication and the training of private providers as well as the sale and distribution of Malarine, the recommended ACT, and Malacheck, the RDT. This paper describes and evaluates this experience by drawing on the results of household and provider surveys conducted since the start of the programme. The available evidence suggests that providers' and consumers' awareness of Malarine increased rapidly, but that of Malacheck much less so. In addition, improvements in ACT and RDT availability and uptake were relatively slow, particularly in more remote areas.The lack of standardization in the survey methods and the gaps in the data highlight the importance of establishing a clear system for monitoring and evaluation for similar initiatives. Despite these limitations, a number of important lessons can still be learnt. These include the importance of a comprehensive communications strategy and of a sustained and reliable supply of products, with attention to the geographical reach of both. Other important challenges relate to the difficulty in incentivising providers and consumers not only to choose the recommended drug, but to precede this with a confirmatory blood test and ensure that providers adhere to the test results and patients to the treatment regime. In Cambodia, this is particularly complicated due to problems inherent to the drug itself and the emergence of artemisinin resistance.Malaria Journal 08/2011; 10:243. · 3.19 Impact Factor -
Article: Randomized trials of artemisinin-piperaquine, dihydroartemisinin-piperaquine phosphate and artemether-lumefantrine for the treatment of multi-drug resistant falciparum malaria in Cambodia-Thailand border area.
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ABSTRACT: Drug resistance of falciparum malaria is a global problem. Sulphadoxine/pyrimethamine-resistant and mefloquine-resistant strains of falciparum malaria have spread in Southeast Asia at lightning speed in 1980s-1990s, and the Cambodia-Thailand border is one of the malaria epidemic areas with the most severe forms of multi-drug resistant falciparum malaria. Artemisinin-piperaquine (AP), dihydroartemisinin-piperaquine phosphate (DHP) and artemether-lumefantrine (AL) were used to treat 110, 55 and 55 uncomplicated malaria patients, respectively. The total dosage for adults is 1,750 mg (four tablets, twice over 24 hours) of AP, 2,880 mg (eight tablets, four times over two days) of DHP, and 3,360 mg (24 tablets, six times over three days) of AL. The 28-day cure rate, parasite clearance time, fever clearance time, and drug tolerance of patients to the three drugs were compared. All of the above methods were consistent with the current national guidelines. The mean parasite clearance time was similar in all three groups (66.7 ± 21.9 hrs, 65.6 ± 27.3 hrs, 65.3 ± 22.5 hrs in AP, DHP and AL groups, respectively), and there was no remarkable difference between them; the fever clearance time was also similar (31.6 ± 17.7 hrs, 34.6 ± 21.8 hrs and 36.9 ± 15.4 hrs, respectively). After following up for 28-days, the cure rate was 95.1%(97/102), 98.2%(54/55) and 82.4%(42/51); and the recrudescence cases was 4.9%(5/102), 1.8%(1/55) and 17.6%(9/51), respectively. Therefore, the statistical data showed that 28-day cure rate in AP and DHP groups was superior to AL group obviously.The patients had good tolerance to all the three drugs, and some side effects (anoxia, nausea, vomiting, headache and dizziness) could be found in every group and they were self-limited; patients in control groups also had good tolerance to DHP and AL, there was no remarkable difference in the three groups. AP, DHP and AL all remained efficacious treatments for the treatment of falciparum malaria in Cambodia-Thailand border area. However, in this particular setting, the AP regimen turned out to be favourable in terms of efficacy and effectiveness, simplicity of administration, cost and compliance. The trial was registered at Chinese Clinical Trial Register under identifier 2005L01041.Malaria Journal 08/2011; 10:231. · 3.19 Impact Factor -
Article: Artemisinin resistance in Plasmodium falciparum is associated with an altered temporal pattern of transcription.
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ABSTRACT: Artemisinin resistance in Plasmodium falciparum malaria has emerged in Western Cambodia. This is a major threat to global plans to control and eliminate malaria as the artemisinins are a key component of antimalarial treatment throughout the world. To identify key features associated with the delayed parasite clearance phenotype, we employed DNA microarrays to profile the physiological gene expression pattern of the resistant isolates. In the ring and trophozoite stages, we observed reduced expression of many basic metabolic and cellular pathways which suggests a slower growth and maturation of these parasites during the first half of the asexual intraerythrocytic developmental cycle (IDC). In the schizont stage, there is an increased expression of essentially all functionalities associated with protein metabolism which indicates the prolonged and thus increased capacity of protein synthesis during the second half of the resistant parasite IDC. This modulation of the P. falciparum intraerythrocytic transcriptome may result from differential expression of regulatory proteins such as transcription factors or chromatin remodeling associated proteins. In addition, there is a unique and uniform copy number variation pattern in the Cambodian parasites which may represent an underlying genetic background that contributes to the resistance phenotype. The decreased metabolic activities in the ring stages are consistent with previous suggestions of higher resilience of the early developmental stages to artemisinin. Moreover, the increased capacity of protein synthesis and protein turnover in the schizont stage may contribute to artemisinin resistance by counteracting the protein damage caused by the oxidative stress and/or protein alkylation effect of this drug. This study reports the first global transcriptional survey of artemisinin resistant parasites and provides insight to the complexities of the molecular basis of pathogens with drug resistance phenotypes in vivo.BMC Genomics 08/2011; 12:391. · 4.07 Impact Factor -
Article: Adult Opisthorchis viverrini flukes in humans, Takeo, Cambodia.
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ABSTRACT: To the Editor: Opisthorchis viverrini and Clonorchis sinensis, the 2 major species of small liver flukes (family Opisthorchiidae), cause chronic inflammation in the bile duct, which leads to cholangitis and cirrhosis of the liver, and are a predisposing factor for cholangiocarcinoma (1). Human infections with O. viverrini flukes are found along riverside areas of Indochina (Thailand, Lao People's Democratic Republic [PDR], and Vietnam) (2).Emerging Infectious Diseases 07/2011; 17(7):1302-4. · 6.79 Impact Factor -
Article: Echinostoma ilocanum infection in Oddar Meanchey Province, Cambodia.
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ABSTRACT: Fecal examinations using the Kato Katz technique were performed on a total of 1,287 villagers (945 students and 342 general inhabitants) of Oddar Meanchey Province, Cambodia in May 2007 and November 2009. The overall intestinal helminth egg positive rate was 23.9%, and the most prevalent helminth species was hookworms (21.6%). Other helminth eggs detected included echinostomes (1.0%), Enterobius vermicularis (0.8%), small trematode eggs (0.7%), which may include Opisthorchis viverrini and Haplorchis spp., and Hymenolepis nana (0.4%). In order to recover adult echinostomes, we treated 2 patients with 10-15 mg/kg praziquantel and purged. Total 14 adult echinostomes, 1 and 13 worms from each patient, were collected. The echinostomes characteristically had 49-51 collar spines and 2 round or slightly lobated testes. They were identified as Echinostoma ilocanum (Garrison, 1908) Odhner, 1911. So far as literature are concerned, this is the first record on the discovery of human E. ilocanum infection in Cambodia.The Korean Journal of Parasitology 06/2011; 49(2):187-90. · 1.04 Impact Factor -
Article: Molecular identification of Taenia tapeworms by Cox1 gene in Koh Kong, Cambodia.
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ABSTRACT: We collected fecal samples from 21 individuals infected with Taenia tapeworms in Koh Kong Province, Cambodia, and performed nucleotide sequencing of the cox1 gene and multiplex PCR on the eggs for DNA differential diagnosis of human Taenia tapeworms. Genomic DNA was extracted from the eggs of a minimum number of 10 isolated from fecal samples. Using oligonucleotide primers Ta7126F, Ts7313F, Tso7466F, and Rev7915, the multiplex PCR assay proved useful for differentially diagnosing Taenia solium, Taenia saginata, and Taenia asiatica based on 706, 629, and 474 bp bands, respectively. All of the Taenia specimens from Kho Kong, Cambodia, were identified as either T. saginata (n=19) or T. solium (n=2) by cox1 sequencing and multiplex PCR.The Korean Journal of Parasitology 06/2011; 49(2):195-7. · 1.04 Impact Factor -
Article: Intrahost modeling of artemisinin resistance in Plasmodium falciparum.
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ABSTRACT: Artemisinin-resistant Plasmodium falciparum malaria has emerged in western Cambodia. Resistance is characterized by prolonged in vivo parasite clearance times (PCTs) following artesunate treatment. The biological basis is unclear. The hypothesis that delayed parasite clearance results from a stage-specific reduction in artemisinin sensitivity of the circulating young asexual parasite ring stages was examined. A mathematical model was developed, describing the intrahost parasite stage-specific pharmacokinetic-pharmacodynamic relationships. Model parameters were estimated using detailed pharmacokinetic and parasite clearance data from 39 patients with uncomplicated falciparum malaria treated with artesunate from Pailin (western Cambodia) where artemisinin resistance was evident and 40 patients from Wang Pha (northwestern Thailand) where efficacy was preserved. The mathematical model reproduced the observed parasite clearance for each patient with an accurate goodness of fit (rmsd: 0.03-0.67 in log(10) scale). The parameter sets that provided the best fits with the observed in vivo data consist of a highly conserved concentration-effect relationship for the trophozoite and schizont parasite stages, but a variable relationship for the ring stages. The model-derived assessment suggests that the efficacy of artesunate on ring stage parasites is reduced significantly in Pailin. This result supports the hypothesis that artemisinin resistance mainly reflects reduced ring-stage susceptibility and predicts that doubling the frequency of dosing will accelerate clearance of artemisinin-resistant parasites.Proceedings of the National Academy of Sciences 01/2011; 108(1):397-402. · 9.68 Impact Factor -
Article: Echinostoma revolutum infection in children, Pursat Province, Cambodia.
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ABSTRACT: To determine the prevalence of helminthic infections in Pursat Province, Cambodia, we tested fecal specimens from 471 children, 10-14 years of age, in June 2007. The prevalence of infection with echinostome flukes ranged from 7.5% to 22.4% in 4 schools surveyed. Adult worms were identified as Echinostoma revolutum.Emerging Infectious Diseases 01/2011; 17(1):117-9. · 6.79 Impact Factor -
Article: Pyronaridine-artesunate versus chloroquine in patients with acute Plasmodium vivax malaria: a randomized, double-blind, non-inferiority trial.
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ABSTRACT: New antimalarials are needed for P. vivax and P. falciparum malaria. This study compared the efficacy and safety of pyronaridine-artesunate with that of chloroquine for the treatment of uncomplicated P. vivax malaria. This phase III randomized, double-blind, non-inferiority trial included five centers across Cambodia, Thailand, India, and Indonesia. In a double-dummy design, patients (aged >3-≤ 60 years) with microscopically confirmed P. vivax mono-infection were randomized (1:1) to receive pyronaridine-artesunate (target dose 7.2:2.4 mg/kg to 13.8:4.6 mg/kg) or chloroquine (standard dose) once daily for three days. Each treatment group included 228 randomized patients. Outcomes for the primary endpoint, Day-14 cure rate in the per-protocol population, were 99.5%, (217/218; 95%CI 97.5, 100) with pyronaridine-artesunate and 100% (209/209; 95%CI 98.3, 100) with chloroquine. Pyronaridine was non-inferior to chloroquine: treatment difference -0.5% (95%CI -2.6, 1.4), i.e., the lower limit of the 2-sided 95%CI for the treatment difference was greater than -10%. Pyronaridine-artesunate cure rates were non-inferior to chloroquine for Days 21, 28, 35 and 42. Parasite clearance time was shorter with pyronaridine-artesunate (median 23.0 h) versus chloroquine (32.0 h; p<0.0001), as was fever clearance time (median 15.9 h and 23.8 h, respectively; p = 0.0017). Kaplan-Meier estimates of post-baseline P. falciparum infection incidence until Day 42 were 2.5% with pyronaridine-artesunate, 6.1% with chloroquine (p = 0.048, log-rank test). Post-baseline P. vivax or P. falciparum infection incidence until Day 42 was 6.8% and 12.4%, respectively (p = 0.022, log rank test). There were no deaths. Adverse events occurred in 92/228 (40.4%) patients with pyronaridine-artesunate and 72/228 (31.6%) with chloroquine. Mild and transient increases in hepatic enzymes were observed for pyronaridine-artesunate. Pyronaridine-artesunate efficacy in acute uncomplicated P. vivax malaria was at least that of chloroquine. As pyronaridine-artesunate is also efficacious against P. falciparum malaria, this combination has potential utility as a global antimalarial drug. Clinicaltrials.gov NCT00440999.PLoS ONE 01/2011; 6(1):e14501. · 4.09 Impact Factor -
Article: Efficacy of sodium metaperiodate (SMP)-ELISA for the serodiagnosis of schistosomiasis mekongi.
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ABSTRACT: Schistosomiasis mekongi is an important public health issue in endemic countries. In this study, we evaluated an indirect immunodiagnostic ELISA method using Schistosoma mekongi soluble egg antigen. Sodium metaperiodate (SMP)-ELISA was utilized in order to remove the glycosylated epitopes responsible for false positive reactions and the results using this method were compared with those using conventional ELISA (conv-ELISA). Forty-two serum samples from schistosomiasis mekongi egg-positive patients and 100 serum samples from schistosomiasis-negative Cambodian subjects were tested using both ELISA methods. The ranges of ELISA values for positive and negative sera were distinct on SMP-ELISA, but the ranges of the two groups of sera overlapped on conv-ELISA. Therefore, diagnostic criteria may be established based on the highest ELISA value on negative sera and the lowest ELISA value on positive sera. In the present study, both the sensitivity and specificity of SMP-ELISA reached 100% using the criteria in which an ELISA value > or = 0.2 was positive.The Southeast Asian journal of tropical medicine and public health 01/2011; 42(1):25-33. · 0.60 Impact Factor -
Article: Plasmodium falciparum gametocyte carriage is associated with subsequent Plasmodium vivax relapse after treatment.
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ABSTRACT: Mixed P. falciparum/P. vivax infections are common in southeast Asia. When patients with P. falciparum malaria are treated and followed for several weeks, a significant proportion will develop P. vivax malaria. In a combined analysis of 243 patients recruited to two malaria treatment trials in western Cambodia, 20/43 (47%) of those with P. falciparum gametocytes on admission developed P. vivax malaria by Day 28 of follow-up. The presence of Pf gametocytes on an initial blood smear was associated with a 3.5-fold greater rate of vivax parasitemia post-treatment (IRR = 3.5, 95% CI 2.0-6.0, p<0.001). The increased rate of post-treatment P. vivax infection persisted when correlates of exposure and immunity such as a history of malaria, male gender, and age were controlled for (IRR = 3.0, 95% CI 1.9-4.7, p<0.001). Polymerase chain reaction (PCR) confirmed that only a low proportion of subjects (5/55 or 9.1%) who developed vivax during follow-up had detectable Pv parasites in the peripheral blood at baseline. Molecular detection of falciparum gametocytes by reverse transcriptase PCR in a subset of patients strengthened the observed association, while PCR detection of Pv parasitemia at follow-up was similar to microscopy results. These findings suggest that the majority of vivax infections arising after treatment of falciparum malaria originate from relapsing liver-stage parasites. In settings such as western Cambodia, the presence of both sexual and asexual forms of P. falciparum on blood smear at presentation with acute falciparum malaria serves as a marker for possible occult P. vivax coinfection and subsequent relapse. These patients may benefit from empiric treatment with an 8-aminoquinolone such as primaquine.PLoS ONE 01/2011; 6(4):e18716. · 4.09 Impact Factor
Top co-authors
Top Journals
Institutions
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2012
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Yonsei University Hospital
Seoul, Seoul, South Korea -
Gyeongsang National University
- Department of Parasitology and Institute of Health Sciences
Chinju, South Gyeongsang, South Korea
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2009–2012
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Mahidol University
- • Faculty of Tropical Medicine
- • Department of Clinical Tropical Medicine
Bangkok, Bangkok, Thailand
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2010–2011
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London School of Hygiene and Tropical Medicine
- Department of Global Health and Development
London, ENG, United Kingdom -
Phramongkutklao Hostpital
Bangkok, Bangkok, Thailand
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2009–2011
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Armed Forces Research Institute of Medical Sciences
Bangkok, Bangkok, Thailand
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2002–2011
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Dokkyo Medical University
- Department of Tropical Medicine and Parasitology
Tochigi, Tochigi-ken, Japan
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2009–2010
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Cambodia National Malaria Center
Phnom Penh, Krong Phnum Penh, Cambodia
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2004
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University of Tsukuba
- Institute of Basic Medical Sciences
Tsukuba, Ibaraki-ken, Japan
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