264 results on '"Lek, Dysoley"'
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2. Impact of targeted drug administration and intermittent preventive treatment for forest goers using artesunate–pyronaridine to control malaria outbreaks in Cambodia
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Lek, Dysoley, Sokomar, Nguon, Samphornarann, Top, Rideout, Jeanne, Hassan, Saad El-Din, Bunkea, Tol, Ath, Saing Sam, Seng, Rothpisey, Hustedt, John, Peto, Thomas J., Hughes, Jayme, Kimmen, Ke, Dy, Khoy, and Adhikari, Bipin
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- 2024
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3. Radical cure for Plasmodium vivax malaria after G6PD qualitative testing in four provinces in Cambodia, results from Phase I implementation
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Lek, Dysoley, Tsai, Yu-Cheng, Hirano, Jillian, Sovannaroth, Siv, Bunreth, Voeurng, Vonn, Prak, Vannthen, Or, Bunkea, Tol, Samphornarann, Top, Sokomar, Nguon, Sarath, Mak, Kheang, Soy Ty, Wong, Evelyn, Burbach, Michelle K., Hughes, Jayme, and Rekol, Huy
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- 2024
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4. Using serological diagnostics to characterize remaining high-incidence pockets of malaria in forest-fringe Cambodia
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Grimée, Mathilde, Tacoli, Costanza, Sandfort, Mirco, Obadia, Thomas, Taylor, Aimee R., Vantaux, Amélie, Robinson, Leanne J., Lek, Dysoley, Longley, Rhea J., Mueller, Ivo, Popovici, Jean, White, Michael T., and Witkowski, Benoît
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- 2024
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5. A youth advisory group on health and health research in rural Cambodia
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Mom Ean, Rupam Tripura, Phann Sothea, Uch Savoeun, Thomas J. Peto, Sam Bunthynn, James J. Callery, Ung Soviet, Lek Dysoley, Phaik Yeong Cheah, and Bipin Adhikari
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Youth groups ,community engagement ,health ,research ,skills ,trust ,Medical philosophy. Medical ethics ,R723-726 ,Social sciences (General) ,H1-99 - Abstract
Engaging young people in health research has been promoted globally. We explored the outcomes of youth advisory group on health and research engagement (YAGHRE) in rural Cambodia. In May 2021, the Mahidol Oxford Tropical Medicine Research Unit (MORU) partnered with a local health centre and a secondary school to establish a youth engagement group. Ten students underwent training and led health engagement activities in schools and communities. Activities were documented as field notes and audio-visual materials which underwent content analysis using theory of change supplemented by iterative discussions with YAGHRE members and stakeholders. Five major outcomes were identified: 1. Increased respect. Engagement activities developed based on input from students and stakeholders may have fostered greater respect. 2. Built trust and relationships. Frequent visits to MORU’s laboratory and interactions with researchers appeared to contribute to the building of trust and relationship. 3. Improved health and research literacy. Learning new health and research topics, through participatory activities may have improved literacy; 4. Improved uptake of health and research interventions. Health promotional activities and communication with research participants potentially increased the uptake of interventions; 5. Improved community health. YAGHRE’s health promotional interventions may have contributed in enhancing community’s health.
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- 2024
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6. Evaluation of an electronic clinical decision support algorithm to improve primary care management of acute febrile illness in rural Cambodia: protocol for a cluster-randomised trial
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Arjun Chandna, Greg Fegan, Abhijit Mishra, Yoel Lubell, Marco Liverani, Bipin Adhikari, Rusheng Chew, Nicholas P J Day, Naomi Waithira, Richard James Maude, Rupam Tripura, Thomas Julian Peto, James John Callery, Lek Dysoley, Moul Vanna, Elke Wynberg, Huy Rekol, and Chea Nguon
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Medicine - Abstract
Introduction Acute febrile illness (AFI), traditionally attributed to malaria, is a common reason for seeking primary healthcare in rural South and Southeast Asia. However, malaria transmission has declined while health workers are often poorly equipped to manage non-malarial AFIs. This results in indiscriminate antibiotic prescribing and care escalation, which promotes antibiotic resistance and may increase healthcare costs. To address this problem, an electronic clinical decision support algorithm (eCDSA) called ‘Electronic clinical Decision support for Acute fever Management (EDAM)’ has been developed for primary health workers which integrates clinical, epidemiological and vital sign data with simple point-of-care tests to produce a diagnosis and management plan.Methods and analysis This is a pragmatic cluster-randomised trial aiming to assess the effect of EDAM and related training on antibiotic prescribing rates in rural Cambodian primary health centres (PHCs) as the primary outcome, along with a range of secondary outcomes including safety. Patients with AFI are eligible for recruitment if they are aged ≥1 year. A cluster is defined as a PHC and PHCs will be randomised to control (standard of care) and intervention (EDAM and associated training) arms, with 15 PHCs per arm. Patients will be followed up after 7 days to ascertain the safety profile of EDAM. Each PHC will recruit 152 patients (total 4560), based on a baseline antibiotic prescription rate of 25% and expected reduction to 17.5% with EDAM.Ethics and dissemination Results will be published in international peer-reviewed journals to inform the design of future versions of EDAM and of future trials of similar eCDSAs and other digital health interventions targeted towards rural populations. This study was approved by the Oxford University Tropical Research Ethics Committee (550-23) and the Cambodian National Ethics Committee for Health Research (395-NECHR).Trial registration number International Standard Randomized Controlled Trial Number Registry (ISRCTN15157105).
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- 2024
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7. Expanding the roles of community health workers to sustain programmes during malaria elimination: a meeting report on operational research in Southeast Asia
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Lek Dysoley, James J. Callery, Voeurng Bunreth, Moul Vanna, Chan Davoeung, Yok Sovann, Sles You, Sam Ol, Rupam Tripura, Rusheng Chew, Arjun Chandna, Céline Christiansen-Jucht, Jayme Hughes, Nguon Sokomar, Top Sophornarann, Jeanne Rideout, Tat Veyvath, Oum Sarith, Thaung Puthy, Hay Sothearoth, Sen Sam An, Sazid Ibna Zaman, Lorenz von Seidlein, Lim Vanthy, Preap Sodavuth, Chrun Vannak, Arjen M. Dondorp, Yoel Lubell, Richard J. Maude, Thomas J. Peto, and Bipin Adhikari
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Malaria ,Community health workers ,Village malaria workers ,Roles ,Malaria elimination ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract In Southeast Asia malaria elimination is targeted by 2030. Cambodia aims to achieve this by 2025, driven in large part by the urgent need to control the spread of artemisinin-resistant falciparum malaria infections. Rapid elimination depends on sustaining early access to diagnosis and effective treatment. In much of Cambodia, rapid elimination will rely on a village malaria worker (VMW) network. Yet as malaria declines and is no longer a common cause of febrile illness, VMWs may become less popular with febrile patients, as VMWs do not diagnose or treat other conditions at present. There is a risk that VMWs become inactive and malaria rebounds before the complete interruption of transmission is achieved. During 2021–23 a large-scale operational research study was conducted in western Cambodia to explore how a VMW network could be sustained by including health activities that cover non-malarial illnesses to encourage febrile patients to continue to attend. 105 VMWs received new rapid diagnostic tests (including dengue antigen–antibody and combined malaria/C-reactive protein tests), were trained in electronic data collection, and attended health education packages on hygiene and sanitation, disease surveillance and first aid, management of mild illness, and vaccination and antenatal care. In August 2023 the National Malaria Control Programme of Cambodia convened a stakeholder meeting in Battambang, Cambodia. Findings from the study were reviewed in the context of current malaria elimination strategies. The discussions informed policy options to sustain the relevance of the VMW network in Cambodia, and the potential for its integration with other health worker networks. This expansion could ensure VMWs remain active and relevant until malaria elimination is accomplished.
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- 2024
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8. Defining the hidden burden of disease in rural communities in Bangladesh, Cambodia and Thailand: a cross-sectional household health survey protocol
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Yoel Lubell, Marco Liverani, Rusheng Chew, Nicholas P J Day, Naomi Waithira, Sue Lee, Akramul Islam, Shayla Islam, Elizabeth M Batty, Richard James Maude, Rupam Tripura, Thomas Julian Peto, Meiwen Zhang, Lek Dysoley, Nan Shwe Nwe Htun, Carlo Perrone, Aninda Sen, Amit Kumer Neogi, Watcharintorn Thongpiam, Jantana Wongsantichon, Chonticha Menggred, Sazid Ibna Zaman, and Stuart Blacksell
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Medicine - Abstract
Introduction In low-income and middle-income countries in Southeast Asia, the burden of diseases among rural population remains poorly understood, posing a challenge for effective healthcare prioritisation and resource allocation. Addressing this knowledge gap, the South and Southeast Asia Community-based Trials Network (SEACTN) will undertake a survey that aims to determine the prevalence of a wide range of non-communicable and communicable diseases, as one of the key initiatives of its first project—the Rural Febrile Illness project (RFI). This survey, alongside other RFI studies that explore fever aetiology, leading causes of mortality, and establishing village and health facility maps and profiles, will provide an updated epidemiological background of the rural areas where the network is operational.Methods and analysis During 2022–2023, a cross-sectional household survey will be conducted across three SEACTN sites in Bangladesh, Cambodia and Thailand. Using a two-stage cluster-sampling approach, we will employ a probability-proportional-to-size sample method for village, and a simple random sample for household, selection, enrolling all members from the selected households. Approximately 1500 participants will be enrolled per country. Participants will undergo questionnaire interview, physical examination and haemoglobin point-of-care testing. Blood samples will be collected and sent to central laboratories to test for chronic and acute infections, and biomarkers associated with cardiovascular disease, and diabetes. Prevalences will be presented as an overall estimate by country, and stratified and compared across sites and participants’ sociodemographic characteristics. Associations between disease status, risk factors and other characteristics will be explored.Ethics and dissemination This study protocol has been approved by the Oxford Tropical Research Ethics Committee, National Research Ethics Committee of Bangladesh Medical Research Council, the Cambodian National Ethics Committee for Health Research, the Chiang Rai Provincial Public Health Research Ethical Committee. The results will be disseminated via the local health authorities and partners, peer-reviewed journals and conference presentations.Trial registration number NCT05389540.
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- 2024
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9. Rethinking village malaria workers in Cambodia: Perspectives from the communities, programme managers, and international stakeholders.
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Long Heng Orng, Monnaphat Jongdeepaisal, Panarasri Khonputsa, Lek Dysoley, Siv Sovannaroth, Thomas J Peto, James J Callery, Christopher Pell, Richard J Maude, and Marco Liverani
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Public aspects of medicine ,RA1-1270 - Abstract
Since the early 2000s, malaria cases in Cambodia have declined steadily. Village malaria workers (VMWs) have played a critical role in reducing malaria transmission and progress towards malaria elimination. To prevent malaria re-establishment, however, implementation strategies need to consider carefully the changing healthcare needs in the communities as well as challenges to, and opportunities for, programme adaptation. We conducted in-depth interviews with a diverse range of stakeholders involved in the planning or implementation of the VMW programme in Cambodia, to elicit their views and experiences about health priorities in the communities, the public health value of VMWs and community-based care, and prospects for future programme development. Respondents included managers and implementers involved in the VMW programme at the central and provincial level (n = 9), technical officers at international agencies in Cambodia (n = 7), international stakeholders in non-governmental and research organisations based in Cambodia or other countries in the region (n = 5), as well as VMWs (n = 10), and community members (n = 16) in six endemic communes of Kravanh District, Pursat Province. In Kravanh, we also conducted four focus group discussions with 19 community members who had previous experience of malaria. The qualitative dataset was analysed using a thematic approach. VMWs, particularly mobile malaria workers tasked with active case detection among forest workers, were deemed necessary to maintain effective malaria control. However, there was a clear demand in the communities for additional services including treatment for common illnesses, monitoring of blood pressure and blood sugar levels, and relief of general symptoms through medication, such as for fever, headache, and stomach pain. Programme managers and international stakeholders agreed that the VMW programme needs a rethinking of the current implementation model to ensure continued uptake, relevance, and motivation of VMWs. Suggestions for add-on activities included adoption of new tests for febrile illnesses such as dengue and chikungunya, and screening for the prevention and monitoring of non-communicable diseases. There was emphasis on the needs for more sustainable financing mechanisms and integration with the existing community health infrastructure. The potential expansion of VMW services will benefit from the continued involvement of external donors and partners for technical and financial support. However, the implementation strategy should consider since the outset opportunities for enhanced local ownership and health system integration. To maintain domestic political momentum and access new potential sources of domestic funding, further programme development should align with national health priorities and the ongoing process of administrative decentralisation, while being responsive to changing public health needs within the communities.
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- 2024
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10. Strategies for deploying triple artemisinin-based combination therapy in the Greater Mekong Subregion
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de Haan, Freek, Amaratunga, Chanaki, Thi, Van Anh Cao, Orng, Long Heng, Vonglokham, Manithong, Quang, Thieu Nguyen, Lek, Dysoley, Boon, Wouter P. C., Dondorp, Arjen M., and Moors, Ellen H. M.
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- 2023
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11. An active and targeted survey reveals asymptomatic malaria infections among high-risk populations in Mondulkiri, Cambodia
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Doum, Dyna, Mclver, David J., Hustedt, John, Hii, Jeffrey, Sovannaroth, Siv, Lek, Dysoley, Richardson, Jason H., Tatarsky, Allison, and Lobo, Neil F.
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- 2023
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12. Genetic surveillance in the Greater Mekong subregion and South Asia to support malaria control and elimination.
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Jacob, Christopher G, Thuy-Nhien, Nguyen, Mayxay, Mayfong, Maude, Richard J, Quang, Huynh Hong, Hongvanthong, Bouasy, Vanisaveth, Viengxay, Ngo Duc, Thang, Rekol, Huy, van der Pluijm, Rob, von Seidlein, Lorenz, Fairhurst, Rick, Nosten, François, Hossain, Md Amir, Park, Naomi, Goodwin, Scott, Ringwald, Pascal, Chindavongsa, Keobouphaphone, Newton, Paul, Ashley, Elizabeth, Phalivong, Sonexay, Maude, Rapeephan, Leang, Rithea, Huch, Cheah, Dong, Le Thanh, Nguyen, Kim-Tuyen, Nhat, Tran Minh, Hien, Tran Tinh, Nguyen, Hoa, Zdrojewski, Nicole, Canavati, Sara, Sayeed, Abdullah Abu, Uddin, Didar, Buckee, Caroline, Fanello, Caterina I, Onyamboko, Marie, Peto, Thomas, Tripura, Rupam, Amaratunga, Chanaki, Myint Thu, Aung, Delmas, Gilles, Landier, Jordi, Parker, Daniel M, Chau, Nguyen Hoang, Lek, Dysoley, Suon, Seila, Callery, James, Jittamala, Podjanee, Hanboonkunupakarn, Borimas, Pukrittayakamee, Sasithon, Phyo, Aung Pyae, Smithuis, Frank, Lin, Khin, Thant, Myo, Hlaing, Tin Maung, Satpathi, Parthasarathi, Satpathi, Sanghamitra, Behera, Prativa K, Tripura, Amar, Baidya, Subrata, Valecha, Neena, Anvikar, Anupkumar R, Ul Islam, Akhter, Faiz, Abul, Kunasol, Chanon, Drury, Eleanor, Kekre, Mihir, Ali, Mozam, Love, Katie, Rajatileka, Shavanthi, Jeffreys, Anna E, Rowlands, Kate, Hubbart, Christina S, Dhorda, Mehul, Vongpromek, Ranitha, Kotanan, Namfon, Wongnak, Phrutsamon, Almagro Garcia, Jacob, Pearson, Richard D, Ariani, Cristina V, Chookajorn, Thanat, Malangone, Cinzia, Nguyen, T, Stalker, Jim, Jeffery, Ben, Keatley, Jonathan, Johnson, Kimberly J, Muddyman, Dawn, Chan, Xin Hui S, Sillitoe, John, Amato, Roberto, Simpson, Victoria, Gonçalves, Sonia, Rockett, Kirk, Day, Nicholas P, Dondorp, Arjen M, Kwiatkowski, Dominic P, and Miotto, Olivo
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asia ,drug resistance ,epidemiology ,genetic surveillance ,global health ,infectious disease ,malaria ,microbiology ,Biochemistry and Cell Biology - Abstract
BackgroundNational Malaria Control Programmes (NMCPs) currently make limited use of parasite genetic data. We have developed GenRe-Mekong, a platform for genetic surveillance of malaria in the Greater Mekong Subregion (GMS) that enables NMCPs to implement large-scale surveillance projects by integrating simple sample collection procedures in routine public health procedures.MethodsSamples from symptomatic patients are processed by SpotMalaria, a high-throughput system that produces a comprehensive set of genotypes comprising several drug resistance markers, species markers and a genomic barcode. GenRe-Mekong delivers Genetic Report Cards, a compendium of genotypes and phenotype predictions used to map prevalence of resistance to multiple drugs.ResultsGenRe-Mekong has worked with NMCPs and research projects in eight countries, processing 9623 samples from clinical cases. Monitoring resistance markers has been valuable for tracking the rapid spread of parasites resistant to the dihydroartemisinin-piperaquine combination therapy. In Vietnam and Laos, GenRe-Mekong data have provided novel knowledge about the spread of these resistant strains into previously unaffected provinces, informing decision-making by NMCPs.ConclusionsGenRe-Mekong provides detailed knowledge about drug resistance at a local level, and facilitates data sharing at a regional level, enabling cross-border resistance monitoring and providing the public health community with valuable insights. The project provides a rich open data resource to benefit the entire malaria community.FundingThe GenRe-Mekong project is funded by the Bill and Melinda Gates Foundation (OPP11188166, OPP1204268). Genotyping and sequencing were funded by the Wellcome Trust (098051, 206194, 203141, 090770, 204911, 106698/B/14/Z) and Medical Research Council (G0600718). A proportion of samples were collected with the support of the UK Department for International Development (201900, M006212), and Intramural Research Program of the National Institute of Allergy and Infectious Diseases.
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- 2021
13. Comparing the roles of community health workers for malaria control and elimination in Cambodia and Tanzania
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Arjen M Dondorp, Bipin Adhikari, Lorenz von Seidlein, Rupam Tripura, Thomas J Peto, Makhily Bayo, James J Callery, Lek Dysoley, Salum Mshamu, and Samwel Gesase
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Medicine (General) ,R5-920 ,Infectious and parasitic diseases ,RC109-216 - Abstract
The reduction of deaths from malaria in sub-Saharan Africa (SSA) is stalling, whereas many countries in Southeast Asia are approaching malaria elimination. We reviewed the role of community health worker (CHW) programmes in malaria control and elimination between regions, with a more detailed description of the programmes in Tanzania and Cambodia. Compared with Tanzania, Cambodia has a much more developed CHW network, which has been pivotal in the near elimination of malaria. In Tanzania, the malaria burden has remained similar over the last decade and treatment continues to rely on healthcare facilities, which provide more limited access to early diagnosis and treatment. Overall, the proportion of malaria cases treated by CHWs is substantially lower in SSA than in Southeast Asia. Even though networks of CHWs are resource intensive and malaria epidemiology differs substantially between countries, there is a strong case for expanding CHW networks in rural SSA to improve early access to effective malaria treatment and reduce the malaria burden.
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- 2023
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14. Glucose 6 Phosphate Dehydrogenase (G6PD) quantitation using biosensors at the point of first contact: a mixed method study in Cambodia
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Bipin Adhikari, Rupam Tripura, Lek Dysoley, James J. Callery, Thomas J. Peto, Chhoeun Heng, Thy Vanda, Ou Simvieng, Sarah Cassidy-Seyoum, Benedikt Ley, Kamala Thriemer, Arjen M. Dondorp, and Lorenz von Seidlein
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Village malaria workers ,Community ,Vivax malaria ,G6PD ,Quantitative ,Radical cure ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Quantitative measurement of Glucose-6-Phosphate Dehydrogenase (G6PD) enzyme activity is critical to decide on appropriate treatment and provision of radical cure regimens for vivax malaria. Biosensors are point-of-care semi-quantitative analysers that measure G6PD enzyme activity. The main objective of this study was to evaluate the operational aspects of biosensor deployment in the hands of village malaria workers (VMWs) in Cambodia over a year. Methods Following initial orientation and training at Kravanh Referral Hospital, each VMW (n = 28) and laboratory technician (n = 5) was provided a biosensor (STANDARD SD Biosensor, Republic of Korea) with supplies for routine use. Over the next 12 months VMWs convened every month for refresher training, to collect supplies, and to recalibrate and test their biosensors. A quantitative self-administered questionnaire was used to assess the skills necessary to use the biosensor after the initial training. Subsequently, VMWs were visited at their location of work for field observation and evaluation using an observer-administered questionnaire. All quantitative questionnaire-based data were analysed descriptively. Semi-structured interviews (SSIs) were conducted among all participants to explore their experience and practicalities of using the biosensor in the field. SSIs were transcribed and translated into English and underwent thematic analysis. Results A total of 33 participants completed the training and subsequently used the biosensor in the community. Quantitative assessments demonstrated progressive improvement in skills using the biosensor. VMWs expressed confidence and enthusiasm to use biosensors in their routine work. Providing G6PD testing at the point of first contact avoids a multitude of barriers patients have to overcome when travelling to health centres for G6PD testing and radical cure. Deploying biosensors in routine work of VMWs was also considered an opportunity to expand and strengthen the role of VMWs as health care providers in the community. VMWs reported practical concerns related to the use of biosensor such as difficulty in using two pipettes, difficulty in extracting the code chip from the machine, and the narrow base of buffer tube. Conclusions VMWs considered the biosensor a practical and beneficial tool in their routine work. Providing VMWs with biosensors can be considered when followed by appropriate training and regular supervision. Providing community management of vivax malaria at the point of first contact could be key for elimination.
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- 2022
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15. Triple therapy with artemether–lumefantrine plus amodiaquine versus artemether–lumefantrine alone for artemisinin-resistant, uncomplicated falciparum malaria: an open-label, randomised, multicentre trial
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Peto, Thomas J, Tripura, Rupam, Callery, James J, Lek, Dysoley, Nghia, Ho Dang Trung, Nguon, Chea, Thuong, Nguyen Thi Huyen, van der Pluijm, Rob W, Dung, Nguyen Thi Phuong, Sokha, Meas, Van Luong, Vo, Long, Le Thanh, Sovann, Yok, Duanguppama, Jureeporn, Waithira, Naomi, Hoglund, Richard M, Chotsiri, Palang, Chau, Nguyen Hoang, Ruecker, Andrea, Amaratunga, Chanaki, Dhorda, Mehul, Miotto, Olivo, Maude, Richard J, Rekol, Huy, Chotivanich, Kesinee, Tarning, Joel, von Seidlein, Lorenz, Imwong, Mallika, Mukaka, Mavuto, Day, Nicholas P J, Hien, Tran Tinh, White, Nicholas J, and Dondorp, Arjen M
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- 2022
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16. Village malaria workers for the community-based management of vivax malaria
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Bipin Adhikari, Rupam Tripura, Thomas J. Peto, James J. Callery, Lorenz von Seidlein, Lek Dysoley, and Arjen M. Dondorp
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Malaria ,Village malaria workers ,Community health workers ,Health system integration ,Community and stakeholder engagement ,Vivax malaria management ,Public aspects of medicine ,RA1-1270 - Abstract
Summary: In Cambodia, malaria cases are on a trajectory towards the goal of malaria elimination by 2025. Vivax malaria is difficult to eliminate because of hypnozoites that can cause relapse. Primaquine, an 8-aminoquinoline, clears hypnozoites but requires testing for glucose-6-phosphate dehydrogenase (G6PD) deficiency. Routine primaquine treatment of vivax malaria has recently been implemented in Cambodia in which Village Malaria Workers (VMWs) diagnose vivax malaria by rapid diagnostic test and refer patients to health centres for G6PD testing and further treatment. Patients are referred back to the VMWs for monitoring adverse symptoms and treatment adherence. This article explores how VMWs’ roles might be optimized for the community-based management of vivax malaria. With sufficient training and supervision, the role of VMWs might be expanded to include G6PD testing, making referral to the health centre superfluous. Community-based management of vivax malaria could increase the coverage of radical cure and accelerate vivax malaria elimination.
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- 2023
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17. Efficacy of three anti-malarial regimens for uncomplicated Plasmodium falciparum malaria in Cambodia, 2009–2011: a randomized controlled trial and brief review
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Lek, Dysoley, Rachmat, Agus, Harrison, Dustin, Chin, Geoffrey, Chaoratanakawee, Suwanna, Saunders, David, Menard, Didier, and Rogers, William O.
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- 2022
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18. Artemisinin resistance in the malaria parasite, Plasmodium falciparum, originates from its initial transcriptional response
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Zhu, Lei, van der Pluijm, Rob W., Kucharski, Michal, Nayak, Sourav, Tripathi, Jaishree, White, Nicholas J., Day, Nicholas P. J., Faiz, Abul, Phyo, Aung Pyae, Amaratunga, Chanaki, Lek, Dysoley, Ashley, Elizabeth A., Nosten, François, Smithuis, Frank, Ginsburg, Hagai, von Seidlein, Lorenz, Lin, Khin, Imwong, Mallika, Chotivanich, Kesinee, Mayxay, Mayfong, Dhorda, Mehul, Nguyen, Hoang Chau, Nguyen, Thuy Nhien Thanh, Miotto, Olivo, Newton, Paul N., Jittamala, Podjanee, Tripura, Rupam, Pukrittayakamee, Sasithon, Peto, Thomas J., Hien, Tran Tinh, Dondorp, Arjen M., and Bozdech, Zbynek
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- 2022
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19. Development of weight and age-based dosing of daily primaquine for radical cure of vivax malaria
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Walter Robert Taylor, Richard M. Hoglund, Pimnara Peerawaranun, Thuy Nhien Nguyen, Tran Tinh Hien, Arnaud Tarantola, Lorenz von Seidlein, Rupam Tripura, Thomas J. Peto, Arjen M. Dondorp, Jordi Landier, Francois H.Nosten, Frank Smithuis, Koukeo Phommasone, Mayfong Mayxay, Soy Ty Kheang, Chy Say, Kak Neeraj, Leang Rithea, Lek Dysoley, Sim Kheng, Sinoun Muth, Arantxa Roca-Feltrer, Mark Debackere, Rick M. Fairhurst, Ngak Song, Philippe Buchy, Didier Menard, Nicholas J. White, Joel Tarning, and Mavuto Mukaka
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Primaquine ,Allometric scaling ,Age-based dosing ,Weight-based dosing ,Plasmodium vivax ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background In many endemic areas, Plasmodium vivax malaria is predominantly a disease of young adults and children. International recommendations for radical cure recommend fixed target doses of 0.25 or 0.5 mg/kg/day of primaquine for 14 days in glucose-6-phosphate dehydrogenase normal patients of all ages. However, for many anti-malarial drugs, including primaquine, there is evidence that children have lower exposures than adults for the same weight-adjusted dose. The aim of the study was to develop 14-day weight-based and age-based primaquine regimens against high-frequency relapsing tropical P. vivax. Methods The recommended adult target dose of 0.5 mg/kg/day (30 mg in a 60 kg patient) is highly efficacious against tropical P. vivax and was assumed to produce optimal drug exposure. Primaquine doses were calculated using allometric scaling to derive a weight-based primaquine regimen over a weight range from 5 to 100 kg. Growth curves were constructed from an anthropometric database of 53,467 individuals from the Greater Mekong Subregion (GMS) to define weight-for-age relationships. The median age associated with each weight was used to derive an age-based dosing regimen from the weight-based regimen. Results The proposed weight-based regimen has 5 dosing bands: (i) 5–7 kg, 5 mg, resulting in 0.71–1.0 mg/kg/day; (ii) 8–16 kg, 7.5 mg, 0.47–0.94 mg/kg/day; (iii) 17–40 kg, 15 mg, 0.38–0.88 mg/kg/day; (iv) 41–80 kg, 30 mg, 0.37–0.73 mg/kg/day; and (v) 81–100 kg, 45 mg, 0.45–0.56 mg/kg/day. The corresponding age-based regimen had 4 dosing bands: 6–11 months, 5 mg, 0.43–1.0 mg/kg/day; (ii) 1–5 years, 7.5 mg, 0.35–1.25 mg/kg/day; (iii) 6–14 years, 15 mg, 0.30–1.36 mg/kg/day; and (iv) ≥ 15 years, 30 mg, 0.35–1.07 mg/kg/day. Conclusion The proposed weight-based regimen showed less variability around the primaquine dose within each dosing band compared to the age-based regimen and is preferred. Increased dose accuracy could be achieved by additional dosing bands for both regimens. The age-based regimen might not be applicable to regions outside the GMS, which must be based on local anthropometric data. Pharmacokinetic data in small children are needed urgently to inform the proposed regimens.
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- 2021
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20. Further evidence needed to change policy for the safe and effective radical cure of vivax malaria: Insights from the 2019 annual APMEN Vivax Working Group meeting
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Varunika Sonani Hapuwatte Ruwanpura, Spike Nowak, Emily Gerth‐Guyette, Minerva Theodora, Lek Dysoley, Mebratom Haile, Koen Peeters Grietens, Ric Norman Price, Caroline Anita Lynch, and Kamala Thriemer
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Asia Pacific ,evidence gaps ,malaria elimination ,malaria health policy ,Plasmodium vivax malaria ,policy implementation ,Political science ,Political science (General) ,JA1-92 - Abstract
Abstract New diagnostics and treatment options for the radical cure of Plasmodium vivax malaria are now available. At the 2019 annual meeting of the Vivax Working Group of the Asia Pacific Malaria Elimination Network, participants took part in a roundtable discussion to identify further evidence required to introduce these new tools into policy and practice. Key gaps identified were accuracy and reliability of glucose‐6‐phosphate‐dehydrogenase deficiency tests, health system capacity, and feasibility and cost effectiveness of novel treatment strategies in routine clinical practice. As expected, there were differences in the priorities between country partners and researcher partners. To achieve the 2030 target for the regional elimination of malaria, evidence to address these issues should be generated as a matter of priority. Review of global guidelines alongside locally generated data will help to ensure the timely revision and optimisation of national treatment guidelines that will be vital to meet regional elimination goals.
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- 2021
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21. Molecular epidemiology of resistance to antimalarial drugs in the Greater Mekong subregion: an observational study
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Imwong, Mallika, Dhorda, Mehul, Myo Tun, Kyaw, Thu, Aung Myint, Phyo, Aung Pyae, Proux, Stephane, Suwannasin, Kanokon, Kunasol, Chanon, Srisutham, Suttipat, Duanguppama, Jureeporn, Vongpromek, Ranitha, Promnarate, Cholrawee, Saejeng, Aungkana, Khantikul, Nardlada, Sugaram, Rungniran, Thanapongpichat, Supinya, Sawangjaroen, Nongyao, Sutawong, Kreepol, Han, Kay Thwe, Htut, Ye, Linn, Khin, Win, Aye Aye, Hlaing, Tin M, van der Pluijm, Rob W, Mayxay, Mayfong, Pongvongsa, Tiengkham, Phommasone, Koukeo, Tripura, Rupam, Peto, Thomas J, von Seidlein, Lorenz, Nguon, Chea, Lek, Dysoley, Chan, Xin Hui S, Rekol, Huy, Leang, Rithea, Huch, Cheah, Kwiatkowski, Dominic P, Miotto, Olivo, Ashley, Elizabeth A, Kyaw, Myat Phone, Pukrittayakamee, Sasithon, Day, Nicholas P J, Dondorp, Arjen M, Smithuis, Frank M, Nosten, Francois H, and White, Nicholas J
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- 2020
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22. Triple artemisinin-based combination therapies versus artemisinin-based combination therapies for uncomplicated Plasmodium falciparum malaria: a multicentre, open-label, randomised clinical trial
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van der Pluijm, Rob W, Tripura, Rupam, Hoglund, Richard M, Phyo, Aung Pyae, Lek, Dysoley, ul Islam, Akhter, Anvikar, Anupkumar R, Satpathi, Parthasarathi, Satpathi, Sanghamitra, Behera, Prativa Kumari, Tripura, Amar, Baidya, Subrata, Onyamboko, Marie, Chau, Nguyen Hoang, Sovann, Yok, Suon, Seila, Sreng, Sokunthea, Mao, Sivanna, Oun, Savuth, Yen, Sovannary, Amaratunga, Chanaki, Chutasmit, Kitipumi, Saelow, Chalermpon, Runcharern, Ratchadaporn, Kaewmok, Weerayuth, Hoa, Nhu Thi, Thanh, Ngo Viet, Hanboonkunupakarn, Borimas, Callery, James J, Mohanty, Akshaya Kumar, Heaton, James, Thant, Myo, Gantait, Kripasindhu, Ghosh, Tarapada, Amato, Roberto, Pearson, Richard D, Jacob, Christopher G, Gonçalves, Sónia, Mukaka, Mavuto, Waithira, Naomi, Woodrow, Charles J, Grobusch, Martin P, van Vugt, Michele, Fairhurst, Rick M, Cheah, Phaik Yeong, Peto, Thomas J, von Seidlein, Lorenz, Dhorda, Mehul, Maude, Richard J, Winterberg, Markus, Thuy-Nhien, Nguyen T, Kwiatkowski, Dominic P, Imwong, Mallika, Jittamala, Podjanee, Lin, Khin, Hlaing, Tin Maung, Chotivanich, Kesinee, Huy, Rekol, Fanello, Caterina, Ashley, Elizabeth, Mayxay, Mayfong, Newton, Paul N, Hien, Tran Tinh, Valeche, Neena, Smithuis, Frank, Pukrittayakamee, Sasithon, Faiz, Abul, Miotto, Olivo, Tarning, Joel, Day, Nicholas PJ, White, Nicholas J, Dondorp, Arjen M, Pyae Phyo, Aung, Thuy-Nhien, Nguyen Thanh, Valecha, Neena, and Day, Nicholas P J
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- 2020
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23. Malaria elimination using the 1-3-7 approach: lessons from Sampov Loun, Cambodia
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Soy Ty Kheang, Siv Sovannaroth, Lawrence M. Barat, Lek Dysoley, Bryan K. Kapella, Ly Po, Sokomar Nguon, John Gimnig, Rida Slot, Top Samphornarann, Seak Kong Meng, Gunawardena Dissanayake, Hala Jassim AlMossawi, Colleen Longacre, and Neeraj Kak
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Malaria ,Malaria elimination ,Surveillance ,1-3-7 approach ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Cambodia has targeted malaria elimination within its territory by 2025 and is developing a model elimination package of strategies and interventions designed to achieve this goal. Methods Cambodia adopted a simplified 1-3-7 surveillance model in the Sampov Loun operational health district in western Cambodia beginning in July 2015. The 1-3-7 approach targets reporting of confirmed cases within one day, investigation of specific cases within three days, and targeted control measures to prevent further transmission within seven days. In Sampov Loun, response measures included reactive case detection (testing of co-travelers, household contacts and family members, and surrounding households with suspected malaria cases), and provision of health education, and insecticide-treated nets. Day 28 follow up microscopy was conducted for all confirmed P. falciparum and P. falciparum-mixed-species malaria cases to assess treatment efficacy. Results The number of confirmed malaria cases in the district fell from 519 in 2015 to 181 in 2017, and the annual parasite incidence (API) in the district fell from 3.21 per 1000 population to 1.06 per 1000 population. The last locally transmitted case of malaria in Sampov Loun was identified in March 2016. In response to the 408 index cases identified, 1377 contacts were screened, resulting in the identification of 14 positive cases. All positive cases occurred among index case co-travelers. Conclusion The experience of the 1-3-7 approach in Sampov Loun indicates that the basic essential malaria elimination package can be feasibly implemented at the operational district level to achieve the goal of malaria elimination in Cambodia and has provided essential information that has led to the refinement of this package.
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- 2020
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24. Ten-year persistence and evolution of Plasmodium falciparum antifolate and anti-sulfonamide resistance markers pfdhfr and pfdhps in three Asian countries.
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Suttipat Srisutham, Wanassanan Madmanee, Jindarat Kouhathong, Kreepol Sutawong, Rupam Tripura, Thomas J Peto, Rob W van der Pluijm, James J Callery, Lek Dysoley, Mayfong Mayxay, Paul N Newton, Tiengkham Pongvongsa, Bouasy Hongvanthong, Nicholas P J Day, Nicholas J White, Arjen M Dondorp, and Mallika Imwong
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Medicine ,Science - Abstract
BackgroundThe amplification of GTP cyclohydrolase 1 (pfgch1) in Plasmodium falciparum has been linked to the upregulation of the pfdhfr and pfdhps genes associated with resistance to the antimalarial drug sulfadoxine-pyrimethamine. During the 1990s and 2000s, sulfadoxine-pyrimethamine was withdrawn from use as first-line treatment in southeast Asia due to clinical drug resistance. This study assessed the temporal and geographic changes in the prevalence of pfdhfr and pfdhps gene mutations and pfgch1 amplification a decade after sulfadoxine-pyrimethamine had no longer been widely used.MethodsA total of 536 P. falciparum isolates collected from clinical trials in Thailand, Cambodia, and Lao PDR between 2008 and 2018 were assayed. Single nucleotide polymorphisms of the pfdhfr and pfdhps genes were analyzed using nested PCR and Sanger sequencing. Gene copy number variations of pfgch1 were investigated using real-time polymerase chain reaction assay.ResultsSequences of the pfdhfr and pfdhps genes were obtained from 96% (517/536) and 91% (486/536) of the samples, respectively. There were 59 distinct haplotypes, including single to octuple mutations. The two major haplotypes observed included IRNI-AGEAA (25%) and IRNL-SGKGA (19%). The sextuple mutation IRNL-SGKGA increased markedly over time in several study sites, including Pailin, Preah Vihear, Ratanakiri, and Ubon Ratchathani, whereas IRNI-AGEAA decreased over time in Preah Vihear, Champasak, and Ubon Ratchathani. Octuple mutations were first observed in west Cambodia in 2011 and subsequently in northeast Cambodia, as well as in southern Laos by 2018. Amplification of the pfgch1 gene increased over time across the region, particularly in northeast Thailand close to the border with Laos and Cambodia.ConclusionDespite the fact that SP therapy was discontinued in Thailand, Cambodia, and Laos decades ago, parasites retained the pfdhfr and pfdhps mutations. Numerous haplotypes were found to be prevalent among the parasites. Frequent monitoring of pfdhfr and pfdhps in these areas is required due to the relatively rapid evolution of mutation patterns.
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- 2022
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25. Glucose-6-Phosphate Dehydrogenase (G6PD) Measurement Using Biosensors by Community-Based Village Malaria Workers and Hospital Laboratory Staff in Cambodia: A Quantitative Study
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Bipin Adhikari, Rupam Tripura, Lek Dysoley, Thomas J. Peto, James J. Callery, Chhoeun Heng, Thy Vanda, Ou Simvieng, Sarah Cassidy-Seyoum, Kamala Thriemer, Arjen M. Dondorp, Benedikt Ley, and Lorenz von Seidlein
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village malaria worker ,biosensor ,vivax malaria ,G6PD ,primaquine ,radical cure ,Medicine - Abstract
Vivax malaria can relapse after an initial infection due to dormant liver stages of the parasite. Radical cure can prevent relapses but requires the measurement of glucose-6-phosphate dehydrogenase enzyme (G6PD) activity to identify G6PD-deficient patients at risk of drug-induced haemolysis. In the absence of reliable G6PD testing, vivax patients are denied radical curative treatment in many places, including rural Cambodia. A novel Biosensor, ‘G6PD Standard’ (SD Biosensor, Republic of Korea; Biosensor), can measure G6PD activity at the point of care. The objectives of this study were to compare the G6PD activity readings using Biosensors by village malaria workers (VMWs) and hospital-based laboratory technicians (LTs), and to compare the G6PD deficiency categorization recommended by the Biosensor manufacturer with categories derived from a locally estimated adjusted male median (AMM) in Kravanh district, Cambodia. Participants were enrolled between 2021 and 2022 in western Cambodia. Each of the 28 VMWs and 5 LTs received a Biosensor and standardized training on its use. The G6PD activities of febrile patients identified in the community were measured by VMWs; in a subset, a second reading was done by LTs. All participants were tested for malaria by rapid diagnostic test (RDT). The adjusted male median (AMM) was calculated from all RDT-negative participants and defined as 100% G6PD activity. VMWs measured activities in 1344 participants. Of that total, 1327 (98.7%) readings were included in the analysis, and 68 of these had a positive RDT result. We calculated 100% activity as 6.4 U/gHb (interquartile range: 4.5 to 7.8); 9.9% (124/1259) of RDT-negative participants had G6PD activities below 30%, 15.2% (191/1259) had activities between 30% and 70%, and 75.0% (944/1259) had activities greater than 70%. Repeat measurements among 114 participants showed a significant correlation of G6PD readings (rs = 0.784, p < 0.001) between VMWs and LTs. Based on the manufacturer’s recommendations, 285 participants (21.5%) had less than 30% activity; however, based on the AMM, 132 participants (10.0%) had less than 30% activity. The G6PD measurements by VMWs and LTs were similar. With the provisions of training, supervision, and monitoring, VMWs could play an important role in the management of vivax malaria, which is critical for the rapid elimination of malaria regionally. Definitions of deficiency based on the manufacturer’s recommendations and the population-specific AMM differed significantly, which may warrant revision of these recommendations.
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- 2023
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26. Publisher Correction: Anopheles ecology, genetics and malaria transmission in northern Cambodia
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Vantaux, Amélie, Riehle, Michelle M., Piv, Eakpor, Farley, Elise J., Chy, Sophy, Kim, Saorin, Corbett, Anneli G., Fehrman, Rachel L., Pepey, Anais, Eiglmeier, Karin, Lek, Dysoley, Siv, Sovannaroth, Mueller, Ivo, Vernick, Kenneth D., and Witkowski, Benoit
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- 2021
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27. Anopheles ecology, genetics and malaria transmission in northern Cambodia
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Vantaux, Amélie, Riehle, Michelle M., Piv, Eakpor, Farley, Elise J., Chy, Sophy, Kim, Saorin, Corbett, Anneli G., Fehrman, Rachel L., Pepey, Anais, Eiglmeier, Karin, Lek, Dysoley, Siv, Sovannaroth, Mueller, Ivo, Vernick, Kenneth D., and Witkowski, Benoit
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- 2021
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28. Determinants of dihydroartemisinin-piperaquine treatment failure in Plasmodium falciparum malaria in Cambodia, Thailand, and Vietnam: a prospective clinical, pharmacological, and genetic study
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van der Pluijm, Rob W, Imwong, Mallika, Chau, Nguyen Hoang, Hoa, Nhu Thi, Thuy-Nhien, Nguyen Thanh, Thanh, Ngo Viet, Jittamala, Podjanee, Hanboonkunupakarn, Borimas, Chutasmit, Kitipumi, Saelow, Chalermpon, Runjarern, Ratchadaporn, Kaewmok, Weerayuth, Tripura, Rupam, Peto, Thomas J, Yok, Sovann, Suon, Seila, Sreng, Sokunthea, Mao, Sivanna, Oun, Savuth, Yen, Sovannary, Amaratunga, Chanaki, Lek, Dysoley, Huy, Rekol, Dhorda, Mehul, Chotivanich, Kesinee, Ashley, Elizabeth A, Mukaka, Mavuto, Waithira, Naomi, Cheah, Phaik Yeong, Maude, Richard J, Amato, Roberto, Pearson, Richard D, Gonçalves, Sónia, Jacob, Christopher G, Hamilton, William L, Fairhurst, Rick M, Tarning, Joel, Winterberg, Markus, Kwiatkowski, Dominic P, Pukrittayakamee, Sasithon, Hien, Tran Tinh, Day, Nicholas PJ, Miotto, Olivo, White, Nicholas J, and Dondorp, Arjen M
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- 2019
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29. The tolerability of single low dose primaquine in glucose-6-phosphate deficient and normal falciparum-infected Cambodians
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Lek Dysoley, Saorin Kim, Sergio Lopes, Nimol Khim, Steven Bjorges, Samphornarann Top, Chea Huch, Huy Rekol, Nelli Westercamp, Mark M. Fukuda, Jimee Hwang, Arantxa Roca-Feltrer, Mavuto Mukaka, Didier Menard, and Walter R. Taylor
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Malaria ,Transmission blocking ,Primaquine ,G6PD deficiency ,Cambodia ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background The WHO recommends single low-dose primaquine (SLDPQ, 0.25 mg/kg body weight) in falciparum-infected patients to block malaria transmission and contribute to eliminating multidrug resistant Plasmodium falciparum from the Greater Mekong Sub region (GMS). However, the anxiety regarding PQ-induced acute haemolytic anaemia in glucose-6-phosphate dehydrogenase deficiency (G6PDd) has hindered its use. Therefore, we assessed the tolerability of SLDPQ in Cambodia to inform national policy. Methods This open randomised trial of dihydroartemisinin-piperaquine (DHAPP) + SLDPQ vs. DHAPP alone recruited Cambodians aged ≥1 year with acute uncomplicated P. falciparum. Randomisation was 4:1 DHAPP+SLDPQ: DHAPP for G6PDd patients and 1:1 for G6PDn patients, according to the results of the qualitative fluorescent spot test. Definitive G6PD status was determined by genotyping. Day (D) 7 haemoglobin (Hb) concentration was the primary outcome measure. Results One hundred nine patients (88 males, 21 females), aged 4–76 years (median 23) were enrolled; 12 were G6PDd Viangchan (9 hemizygous males, 3 heterozygous females). Mean nadir Hb occurred on D7 [11.6 (range 6.4 ─ 15.6) g/dL] and was significantly lower (p = 0.040) in G6PDd (n = 9) vs. G6PDn (n = 46) DHAPP+SLDPQ recipients: 10.9 vs. 12.05 g/dL, Δ = -1.15 (95% CI: -2.24 ─ -0.05) g/dL. Three G6PDn patients had D7 Hb concentrations
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- 2019
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30. Contribution to Malaria Transmission of Symptomatic and Asymptomatic Parasite Carriers in Cambodia
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Vantaux, Amélie, Samreth, Reingsey, Piv, Eakpor, Khim, Nimol, Kim, Saorin, Berne, Laura, Chy, Sophy, Lek, Dysoley, Siv, Sovannaroth, Taylor, Walter R., and Ménard, Didier
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- 2018
31. Quantifying primaquine effectiveness and improving adherence: a round table discussion of the APMEN Vivax Working Group
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Kamala Thriemer, Albino Bobogare, Benedikt Ley, Clarice Samo Gudo, Mohammad Shafiul Alam, Nick M. Anstey, Elizabeth Ashley, J. Kevin Baird, Charlotte Gryseels, Elodie Jambert, Marcus Lacerda, Ferdinand Laihad, Jutta Marfurt, Ayodhia Pitaloka Pasaribu, Jeanne Rini Poespoprodjo, Inge Sutanto, Walter R. Taylor, Christel van den Boogaard, Katherine E. Battle, Lek Dysoley, Prakash Ghimire, Bill Hawley, Jimee Hwang, Wasif Ali Khan, Rose Nani Binti Mudin, Maria Endang Sumiwi, Rukhsana Ahmed, M. M. Aktaruzzaman, Kiran Raj Awasthi, Azucena Bardaji, David Bell, Leonard Boaz, Faustina Helen Burdam, Daniel Chandramohan, Qin Cheng, Keobouphaphone Chindawongsa, Janice Culpepper, Santasabuj Das, Raffy Deray, Meghna Desai, Gonzalo Domingo, Wang Duoquan, Stephan Duparc, Rustini Floranita, Emily Gerth-Guyette, Rosalind E. Howes, Cecilia Hugo, George Jagoe, Elvieda Sariwati, Sanya Tahmina Jhora, Wu Jinwei, Harin Karunajeewa, Enny Kenangalem, Bibek Kumar Lal, Chandra Landuwulang, Emmanuel Le Perru, Sang-Eun Lee, Leo Sora Makita, James McCarthy, Asrat Mekuria, Neelima Mishra, Esau Naket, Simone Nambanya, Johnny Nausien, Thang Ngo Duc, Thuan Nguyen Thi, Rinitis Noviyanti, Daniel Pfeffer, Gao Qi, Annisa Rahmalia, Stephen Rogerson, Iriani Samad, Jetsumon Sattabongkot, Ari Satyagraha, Dennis Shanks, Surender Nath Sharma, Carol Hopkins Sibley, Ali Sungkar, Din Syafruddin, Arunansu Talukdar, Joel Tarning, Feiko ter Kuile, Suman Thapa, Minerva Theodora, Tho Tran Huy, Edward Waramin, Govert Waramori, Adugna Woyessa, Chansuda Wongsrichanalai, Nguyen Xuan Xa, Joon Sup Yeom, Lukas Hermawan, Angela Devine, Spike Nowak, Indra Jaya, Supargiyono Supargiyono, Koen Peeters Grietens, and Ric N. Price
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Vivax malaria ,Plasmodium vivax ,Adherence ,Effectiveness ,Efficacy ,Radical cure ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract The goal to eliminate malaria from the Asia-Pacific by 2030 will require the safe and widespread delivery of effective radical cure of malaria. In October 2017, the Asia Pacific Malaria Elimination Network Vivax Working Group met to discuss the impediments to primaquine (PQ) radical cure, how these can be overcome and the methodological difficulties in assessing clinical effectiveness of radical cure. The salient discussions of this meeting which involved 110 representatives from 18 partner countries and 21 institutional partner organizations are reported. Context specific strategies to improve adherence are needed to increase understanding and awareness of PQ within affected communities; these must include education and health promotion programs. Lessons learned from other disease programs highlight that a package of approaches has the greatest potential to change patient and prescriber habits, however optimizing the components of this approach and quantifying their effectiveness is challenging. In a trial setting, the reactivity of participants results in patients altering their behaviour and creates inherent bias. Although bias can be reduced by integrating data collection into the routine health care and surveillance systems, this comes at a cost of decreasing the detection of clinical outcomes. Measuring adherence and the factors that relate to it, also requires an in-depth understanding of the context and the underlying sociocultural logic that supports it. Reaching the elimination goal will require innovative approaches to improve radical cure for vivax malaria, as well as the methods to evaluate its effectiveness.
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- 2018
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32. Art and theatre for health in rural Cambodia
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Chea Nguon, Lek Dysoley, Chan Davoeung, Yok Sovann, Nou Sanann, Ma Sareth, Pich Kunthea, San Vuth, Kem Sovann, Kayna Kol, Chhouen Heng, Rouen Sary, Thomas J Peto, Rupam Tripura, Renly Lim, and Phaik Yeong Cheah
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Art ,Cambodia ,community engagement ,malaria ,theatre ,Medical philosophy. Medical ethics ,R723-726 ,Social sciences (General) ,H1-99 - Abstract
This article describes our experience using art and theatre to engage rural communities in western Cambodia to understand malaria and support malaria control and elimination. The project was a pilot science–arts initiative to supplement existing engagement activities conducted by local authorities. In 2016, the project was conducted in 20 villages, involved 300 community members and was attended by more than 8000 people. Key health messages were to use insecticide-treated bed-nets and repellents, febrile people should attend village malaria workers, and to raise awareness about the risk of forest-acquired malaria. Building on the experience and lessons learnt in the year prior, the 2017 project which was conducted in 15 villages involved 600 community members and attracted more than 12,000 people. In addition to the malaria theme, upon discussion with local health authorities, secondary theme (infant vaccination) was added to the 2017 project. We learnt the following lessons from our experience in Cambodia: involving local people including children from the beginning of the project and throughout the process is important; messages should be kept simple; it is necessary to take into consideration practical issues such as location and timing of the activities; and that the project should offer something unique to communities.
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- 2018
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33. Expanding the role of village malaria workers in Cambodia: Implementation and evaluation of four health education packages
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Betrian, Mipharny, primary, Umans, Dafne, additional, Vanna, Moul, additional, Ol, Sam, additional, Adhikari, Bipin, additional, Davoeung, Chan, additional, Callery, James J., additional, Sovann, Yok, additional, Peto, Thomas J., additional, Maude, Richard J., additional, van der Pluijm, Rob W., additional, Bunreth, Voeunrung, additional, Grobusch, Martin P., additional, van Vugt, Michèle, additional, Lubell, Yoel, additional, von Seidlein, Lorenz, additional, Dondorp, Arjen M., additional, Sovannaroth, Siv, additional, Lek, Dysoley, additional, and Tripura, Rupam, additional
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- 2023
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34. Activity of Ivermectin and Its Metabolites against Asexual Blood Stage Plasmodium falciparum and Its Interactions with Antimalarial Drugs
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Yipsirimetee, Achaporn, primary, Tipthara, Phornpimon, additional, Hanboonkunupakarn, Borimas, additional, Tripura, Rupam, additional, Lek, Dysoley, additional, Kümpornsin, Krittikorn, additional, Lee, Marcus C. S., additional, Sattabongkot, Jetsumon, additional, Dondorp, Arjen M., additional, White, Nicholas J., additional, Kobylinski, Kevin C., additional, Tarning, Joel, additional, and Chotivanich, Kesinee, additional
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- 2023
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35. Forest malaria in Cambodia: the occupational and spatial clustering of Plasmodium vivax and Plasmodium falciparum infection risk in a cross-sectional survey in Mondulkiri province, Cambodia
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Sandfort, Mirco, Vantaux, Amélie, Kim, Saorin, Obadia, Thomas, Pepey, Anaïs, Gardais, Soazic, Khim, Nimol, Lek, Dysoley, White, Michael, Robinson, Leanne J., Witkowski, Benoit, and Mueller, Ivo
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- 2020
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36. Tools to accelerate falciparum malaria elimination in Cambodia: a meeting report
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Lek, Dysoley, Callery, James J., Nguon, Chea, Debackere, Mark, Sovannaroth, Siv, Tripura, Rupam, Wojnarski, Marius, Piola, Patrice, Khean, Soy Ty, Manion, Kylie, Nguon, Sokomar, Kunkel, Amber, Vernaeve, Lieven, Peto, Thomas J., Dantzer, Emily, Davoeung, Chan, Etienne, William, Dondorp, Arjen M., Tuseo, Luciano, von Seidlein, Lorenz, and Guintran, Jean-Olivier
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- 2020
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37. Therapeutic and Transmission-Blocking Efficacy of Dihydroartemisinin/ Piperaquine and Chloroquine against Plasmodium vivax Malaria, Cambodia
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Popovici, Jean, Vantaux, Amelie, Primault, Lyse, Samreth, Reingsey, Piv, Eak Por, Bin, Sophalai, Kim, Saorin, Lek, Dysoley, Serre, David, and Menard, Didier
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Diseases -- Cambodia -- Health aspects ,Mosquitoes -- Health aspects ,Drug resistance -- Health aspects ,Combination drug therapy -- Health aspects ,Plasmodium falciparum -- Health aspects ,Malaria -- Health aspects ,Health - Abstract
Plasmodium vivax is the most widespread human malaria J. parasite. Almost 2.5 billion persons are at risk for infection in >90 countries (1,2). Since the 1950s-1960s, Southeast Asia has been [...]
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- 2018
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38. Barriers to routine G6PD testing prior to treatment with primaquine
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Benedikt Ley, Kamala Thriemer, Jessica Jaswal, Eugenie Poirot, Mohammad Shafiul Alam, Ching Swe Phru, Wasif Ali Khan, Lek Dysoley, Gao Qi, Chong Chee Kheong, Ummi Kalthom Shamsudin, Ingrid Chen, Jimee Hwang, Roly Gosling, and Ric N. Price
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Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Primaquine is essential for the radical cure of vivax malaria, however its broad application is hindered by the risk of drug-induced haemolysis in individuals with glucose-6-phosphate-dehydrogenase (G6PD) deficiency. Rapid diagnostic tests capable of diagnosing G6PD deficiency are now available, but these are not used widely. Methods A series of qualitative interviews were conducted with policy makers and healthcare providers in four vivax-endemic countries. Routine G6PD testing is not part of current policy in Bangladesh, Cambodia or China, but it is in Malaysia. The interviews were analysed with regard to respondents perceptions of vivax malaria, -primaquine based treatment for malaria and the complexities of G6PD deficiency. Results Three barriers to the roll-out of routine G6PD testing were identified in all sites: (a) a perceived low risk of drug-induced haemolysis; (b) the perception that vivax malaria was benign and accordingly treatment with primaquine was not regarded as a priority; and, (c) the additional costs of introducing routine testing. In Malaysia, respondents considered the current test and treat algorithm suitable and the need for an alternative approach was only considered relevant in highly mobile and hard to reach populations. Conclusions Greater efforts are needed to increase awareness of the benefits of the radical cure of Plasmodium vivax and this should be supported by economic analyses exploring the cost effectiveness of routine G6PD testing.
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- 2017
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39. Challenges for achieving safe and effective radical cure of Plasmodium vivax: a round table discussion of the APMEN Vivax Working Group
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Kamala Thriemer, Benedikt Ley, Albino Bobogare, Lek Dysoley, Mohammad Shafiul Alam, Ayodhia P. Pasaribu, Jetsumon Sattabongkot, Elodie Jambert, Gonzalo J. Domingo, Robert Commons, Sarah Auburn, Jutta Marfurt, Angela Devine, Mohammad M. Aktaruzzaman, Nayeem Sohel, Rinzin Namgay, Tobgyel Drukpa, Surender Nath Sharma, Elvieda Sarawati, Iriani Samad, Minerva Theodora, Simone Nambanya, Sonesay Ounekham, Rose Nanti Binti Mudin, Garib Da Thakur, Leo Sora Makita, Raffy Deray, Sang-Eun Lee, Leonard Boaz, Manjula N. Danansuriya, Santha D. Mudiyanselage, Nipon Chinanonwait, Suravadee Kitchakarn, Johnny Nausien, Esau Naket, Thang Ngo Duc, Ha Do Manh, Young S. Hong, Qin Cheng, Jack S. Richards, Rita Kusriastuti, Ari Satyagraha, Rintis Noviyanti, Xavier C. Ding, Wasif Ali Khan, Ching Swe Phru, Zhu Guoding, Gao Qi, Akira Kaneko, Olivo Miotto, Wang Nguitragool, Wanlapa Roobsoong, Katherine Battle, Rosalind E. Howes, Arantxa Roca-Feltrer, Stephan Duparc, Ipsita Pal Bhowmick, Enny Kenangalem, Jo-Anne Bibit, Alyssa Barry, David Sintasath, Rabindra Abeyasinghe, Carol H. Sibley, James McCarthy, Lorenz von Seidlein, J. Kevin Baird, and Ric N. Price
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Vivax malaria ,P. vivax ,Radical cure ,Primaquine ,APMEN ,Tafenoquine ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract The delivery of safe and effective radical cure for Plasmodium vivax is one of the greatest challenges for achieving malaria elimination from the Asia–Pacific by 2030. During the annual meeting of the Asia Pacific Malaria Elimination Network Vivax Working Group in October 2016, a round table discussion was held to discuss the programmatic issues hindering the widespread use of primaquine (PQ) radical cure. Participants included 73 representatives from 16 partner countries and 33 institutional partners and other research institutes. In this meeting report, the key discussion points are presented and grouped into five themes: (i) current barriers for glucose-6-phosphate deficiency (G6PD) testing prior to PQ radical cure, (ii) necessary properties of G6PD tests for wide scale deployment, (iii) the promotion of G6PD testing, (iv) improving adherence to PQ regimens and (v) the challenges for future tafenoquine (TQ) roll out. Robust point of care (PoC) G6PD tests are needed, which are suitable and cost-effective for clinical settings with limited infrastructure. An affordable and competitive test price is needed, accompanied by sustainable funding for the product with appropriate training of healthcare staff, and robust quality control and assurance processes. In the absence of quantitative PoC G6PD tests, G6PD status can be gauged with qualitative diagnostics, however none of the available tests is currently sensitive enough to guide TQ treatment. TQ introduction will require overcoming additional challenges including the management of severely and intermediately G6PD deficient individuals. Robust strategies are needed to ensure that effective treatment practices can be deployed widely, and these should ensure that the caveats are outweighed by the benefits of radical cure for both the patients and the community. Widespread access to quality controlled G6PD testing will be critical.
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- 2017
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40. The feasibility of novel point-of-care diagnostics for febrile illnesses at health centres in Southeast Asia: a mixed-methods study
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Adella, Fidelis Jacklyn, primary, Vanna, Moul, additional, Adhikari, Bipin, additional, Ol, Sam, additional, Tripura, Rupam, additional, Davoeung, Chan, additional, Callery, James J, additional, Sovann, Yok, additional, Chandna, Arjun, additional, Bunreth, Voeunrung, additional, Asnong, Carina, additional, von Seidlein, Lorenz, additional, Dondorp, Arjen M, additional, Maude, Richard J, additional, Lubell, Yoel, additional, Wills, Bridget, additional, Lek, Dysoley, additional, and Peto, Thomas J, additional
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- 2023
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41. APlasmodium falciparumgenetic cross reveals the contributions ofpfcrtandplasmepsin II/IIIto piperaquine drug resistance
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Kane, John, primary, Li, Xue, additional, Kumar, Sudhir, additional, Button-Simons, Katrina A., additional, Vendrely Brenneman, Katelyn M., additional, Dahlhoff, Haley, additional, Sievert, Mackenzie A.C., additional, Checkley, Lisa A., additional, Shoue, Douglas A., additional, Singh, Puspendra P., additional, Abatiyow, Biley A., additional, Haile, Meseret T., additional, Nair, Shalini, additional, Reyes, Ann, additional, Tripura, Rupam, additional, Peto, Tom, additional, Lek, Dysoley, additional, Kappe, Stefan H.I., additional, Dhorda, Mehul, additional, Nkhoma, Standwell C, additional, Cheeseman, Ian H., additional, Vaughan, Ashley M., additional, Anderson, Timothy J. C., additional, and Ferdig, Michael T., additional
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- 2023
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42. Strategies for deploying triple artemisinin-based combination therapy in the Greater Mekong Subregion
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Innovation and Sustainability, Dep of Sustainable Development, Innovation Studies, de Haan, Freek, Amaratunga, Chanaki, Thi, Van Anh Cao, Orng, Long Heng, Vonglokham, Manithong, Quang, Thieu Nguyen, Lek, Dysoley, Boon, Wouter P. C., Dondorp, Arjen M., Moors, Ellen H. M., Innovation and Sustainability, Dep of Sustainable Development, Innovation Studies, de Haan, Freek, Amaratunga, Chanaki, Thi, Van Anh Cao, Orng, Long Heng, Vonglokham, Manithong, Quang, Thieu Nguyen, Lek, Dysoley, Boon, Wouter P. C., Dondorp, Arjen M., and Moors, Ellen H. M.
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- 2023
43. Forest work and its implications for malaria elimination: a qualitative study
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Sanann, Nou, Peto, Thomas J., Tripura, Rupam, Callery, James J., Nguon, Chea, Bui, Thanh Mai, Nofal, Stephanie D., von Seidlein, Lorenz, Lek, Dysoley, Dondorp, Arjen M., Cheah, Phaik Yeong, and Pell, Christopher
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- 2019
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44. An active and targeted survey reveals asymptomatic malaria infections among high-risk populations in Mondulkiri, Cambodia
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Doum, Dyna, primary, Mclver, David J, additional, Hustedt, John, additional, Hii, Jeffrey, additional, Sovannaroth, Siv, additional, Lek, Dysoley, additional, Richardson, Jason H., additional, Tatarsky, Allison, additional, and Lobo, Neil F., additional
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- 2023
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45. Additional file 1 of An active and targeted survey reveals asymptomatic malaria infections among high-risk populations in Mondulkiri, Cambodia
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Doum, Dyna, Mclver, David J., Hustedt, John, Hii, Jeffrey, Sovannaroth, Siv, Lek, Dysoley, Richardson, Jason H., Tatarsky, Allison, and Lobo, Neil F.
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Additional file 1: Appendix 1. Cross-sectional Survey.
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- 2023
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46. Ten-year persistence and evolution of Plasmodium falciparum antifolate and antisulfonamide resistance markers pfdhfr and pfdhps in three Asian countries
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Suttipat Srisutham, Wanassanan Madmanee, Jindarat Kouhathong, Kreepol Sutawong, Rupam Tripura, Thomas J. Peto, Rob W. van der Pluijm, James J. Callery, Lek Dysoley, Mayfong Mayxay, Paul N. Newton, Tiengkham Pongvongsa, Bouasy Hongvanthong, Nicholas P. J. Day, Nicholas J. White, Arjen M. Dondorp, Mallika Imwong, Intensive Care Medicine, and AII - Infectious diseases
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Multidisciplinary - Abstract
Background The amplification of GTP cyclohydrolase 1 (pfgch1) in Plasmodium falciparum has been linked to the upregulation of the pfdhfr and pfdhps genes associated with resistance to the antimalarial drug sulfadoxine-pyrimethamine. During the 1990s and 2000s, sulfadoxine-pyrimethamine was withdrawn from use as first-line treatment in southeast Asia due to clinical drug resistance. This study assessed the temporal and geographic changes in the prevalence of pfdhfr and pfdhps gene mutations and pfgch1 amplification a decade after sulfadoxine-pyrimethamine had no longer been widely used. Methods A total of 536 P. falciparum isolates collected from clinical trials in Thailand, Cambodia, and Lao PDR between 2008 and 2018 were assayed. Single nucleotide polymorphisms of the pfdhfr and pfdhps genes were analyzed using nested PCR and Sanger sequencing. Gene copy number variations of pfgch1 were investigated using real-time polymerase chain reaction assay. Results Sequences of the pfdhfr and pfdhps genes were obtained from 96% (517/536) and 91% (486/536) of the samples, respectively. There were 59 distinct haplotypes, including single to octuple mutations. The two major haplotypes observed included IRNI-AGEAA (25%) and IRNL-SGKGA (19%). The sextuple mutation IRNL-SGKGA increased markedly over time in several study sites, including Pailin, Preah Vihear, Ratanakiri, and Ubon Ratchathani, whereas IRNI-AGEAA decreased over time in Preah Vihear, Champasak, and Ubon Ratchathani. Octuple mutations were first observed in west Cambodia in 2011 and subsequently in northeast Cambodia, as well as in southern Laos by 2018. Amplification of the pfgch1 gene increased over time across the region, particularly in northeast Thailand close to the border with Laos and Cambodia. Conclusion Despite the fact that SP therapy was discontinued in Thailand, Cambodia, and Laos decades ago, parasites retained the pfdhfr and pfdhps mutations. Numerous haplotypes were found to be prevalent among the parasites. Frequent monitoring of pfdhfr and pfdhps in these areas is required due to the relatively rapid evolution of mutation patterns.
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- 2022
47. G6PD testing and radical cure for Plasmodium vivax in Cambodia: A mixed methods implementation study
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Kheang, Soy Ty, primary, Ridley, Rosemarie, additional, Ngeth, Eng, additional, Ir, Por, additional, Ngor, Pengby, additional, Sovannaroth, Siv, additional, Lek, Dysoley, additional, Phon, Somaly, additional, Kak, Neeraj, additional, and Yeung, Shunmay, additional
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- 2022
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48. Asia-Pacific International Center of Excellence in Malaria Research: Maximizing Impact on Malaria Control Policy and Public Health in Cambodia and Papua New Guinea
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Robinson, Leanne J., primary, Laman, Moses, additional, Makita, Leo, additional, Lek, Dysoley, additional, Dori, Annie, additional, Farquhar, Rachael, additional, Vantaux, Amelie, additional, Witkowski, Benoit, additional, Karl, Stephan, additional, and Mueller, Ivo, additional
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- 2022
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49. Assessment of net lending strategy to better reach mobile and migrant populations in malaria endemic areas of Cambodia
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Lek, Dysoley, Gopinath, Deyer, Ek, Sovann, Heng, Sopheab, Bun, Sreng, Say, Chy, Sokomar, Nguon, Ty, Kheang Soy, and Rekol, Huy
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- 2018
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50. Further evidence needed to change policy for the safe and effective radical cure of vivax malaria: Insights from the 2019 annual APMEN Vivax Working Group meeting
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Lek Dysoley, Varunika Sonani Hapuwatte Ruwanpura, Minerva Theodora, Spike Nowak, Mebratom Haile, Emily Gerth-Guyette, Kamala Thriemer, Koen Peeters Grietens, Caroline A. Lynch, and Ric N. Price
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Special Issue Articles ,Primaquine ,Public Administration ,Sociology and Political Science ,Tafenoquine ,Cost effectiveness ,Asia Pacific ,Strategy and Management ,Economics, Econometrics and Finance (miscellaneous) ,Political science (General) ,radical cure ,chemistry.chemical_compound ,Asia pacific ,Nursing ,Malaria elimination ,parasitic diseases ,medicine ,Political science ,malaria elimination ,Special Issue ,Plasmodium vivax malaria ,medicine.disease ,policy implementation ,chemistry ,malaria health policy ,Political Science and International Relations ,Vivax malaria ,Plasmodium vivax Malaria ,Business ,evidence gaps ,JA1-92 ,Malaria ,medicine.drug - Abstract
New diagnostics and treatment options for the radical cure of Plasmodium vivax malaria are now available. At the 2019 annual meeting of the Vivax Working Group of the Asia Pacific Malaria Elimination Network, participants took part in a roundtable discussion to identify further evidence required to introduce these new tools into policy and practice. Key gaps identified were accuracy and reliability of glucose‐6‐phosphate‐dehydrogenase deficiency tests, health system capacity, and feasibility and cost effectiveness of novel treatment strategies in routine clinical practice. As expected, there were differences in the priorities between country partners and researcher partners. To achieve the 2030 target for the regional elimination of malaria, evidence to address these issues should be generated as a matter of priority. Review of global guidelines alongside locally generated data will help to ensure the timely revision and optimisation of national treatment guidelines that will be vital to meet regional elimination goals.
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- 2021
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