518 results on '"Tran Tinh, Hien"'
Search Results
2. The heterogeneity of symptom reporting across study sites: a secondary analysis of a randomised placebo-controlled multicentre antimalarial trial
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Kamala Thriemer, Robert James Commons, Megha Rajasekhar, Tamiru Shibiru Degaga, Krisin Chand, Nguyen Hoang Chau, Ashenafi Assefa, Mohammad Nader Naddim, Ayodhia Pitaloka Pasaribu, Awab Ghulam Rahim, Inge Sutanto, Tran Tinh Hien, Asrat Hailu, Mohammad Anwar Hasanzai, Lenny L. Ekawati, Adugna Woyessa, Tedla Teferi, Naomi Waithira, Walter R. J. Taylor, Benedikt Ley, Arjen Dondorp, J. Kevin Baird, Nicholas J. White, Nicholas P. Day, Ric N. Price, Julie A. Simpson, and Lorenz von Seidlein
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Clinical trial ,Safety ,Tolerability ,Symptom reporting ,Trial design ,Medicine (General) ,R5-920 - Abstract
Abstract Introduction Symptoms reported following the administration of investigational drugs play an important role in decisions for registration and treatment guidelines. However, symptoms are subjective, and interview methods to quantify them are difficult to standardise. We explored differences in symptom reporting across study sites of a multicentre antimalarial trial, with the aim of informing trial design and the interpretation of safety and tolerability data. Methods Data were derived from the IMPROV trial, a randomised, placebo-controlled double blinded trial of high dose primaquine to prevent Plasmodium vivax recurrence conducted in eight study sites in Afghanistan, Ethiopia, Indonesia and Vietnam. At each follow up visit a 13-point symptom questionnaire was completed. The number and percentage of patients with clinically relevant symptoms following the administration of primaquine or placebo, were reported by study site including vomiting, diarrhoea, anorexia, nausea, abdominal pain and dizziness. Multivariable logistic regression was used to estimate the confounder-adjusted site-specific proportion of each symptom. Results A total of 2,336 patients were included. The greatest variation between sites in the proportion of patients reporting symptoms was for anorexia between day 0 and day 13: 97.3% (361/371) of patients in Arba Minch, Ethiopia, reported the symptom compared with 4.7% (5/106) of patients in Krong Pa, Vietnam. Differences attenuated slightly after adjusting for treatment arm, age, sex, day 0 parasite density and fever; with the adjusted proportion for anorexia ranging from 4.8% to 97.0%. Differences between sites were greater for symptoms graded as mild or moderate compared to those rated as severe. Differences in symptom reporting were greater between study sites than between treatment arms within the same study site. Conclusion Despite standardised training, there was large variation in symptom reporting across trial sites. The reporting of severe symptoms was less skewed compared to mild and moderate symptoms, which are likely to be more subjective. Trialists should clearly distinguish between safety and tolerability outcomes. Differences between trial arms were much less variable across sites, suggesting that the relative difference in reported symptoms between intervention and control group is more relevant than absolute numbers and should be reported when possible. Trial registration Clinicaltrials.gov: NCT01814683; March 20th, 2013.
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- 2023
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3. Pf7: an open dataset of Plasmodium falciparum genome variation in 20,000 worldwide samples [version 1; peer review: 2 approved]
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Mohamed Hassan Abdelraheem, Sonia Goncalves, Lemu Golassa, Tim Anderson, Desmond Omane Acheampong, Enoch Aninagyei, Ifeyinwa Aniebo, Patrick O Ansah, Felix Ansah, Gordon A Awandare, Paulo Arnaldo, Maciej F Boni, Gwladys I Bertin, Peter C Bull, Marielle Bouyou-Akotet, Keobouphaphone Chindavongsa, Edwin Kamau, Huch Cheah, Claire Kamaliddin, Vladimir Corredor, David J Conway, Nicholas Day, Abibatou Konaté, Erin Courtier, Theerarat Kochakarn, Arjen Dondorp, Abdoulaye Djimde, Diego F Echeverry, Seydou Doumbia, Mara Lawniczak, Pharath Lim, Sonia Maria Mauricio Enosse, Oumou Maïga-Ascofaré, Thomas G Egwang, Aung Myint Thu, Mark Fleharty, Jutta Marfurt, Caterina A Fanello, Mark Fukuda, Victor Mobegi, Matthew Forbes, Sara Anne Healy, G L Abby Harrison, Anastasia Hernandez-Koutoucheva, Jason A Hendry, Ivo Mueller, Francis Hombhanje, Harald Noedl, Catherine A Hill, Thuy-Nhien Nguyen, Mazza Hussein, Amanda Hott, Rintis Noviyanti, Scott A Jackson, Abraham Oduro, Deus Ishengoma, Harold Ocholla, Julia Jeans, Jean-Bosco Ouedraogo, Chris G Jacob, Drissa S Konate, Jon Keatley, Francois Nosten, Kolapo Oyebola, Myat P Kyaw, Aminatou Kone, Norbert Peshu, Samuel K Lee, Dennis Kyle, Kovana M Loua, Milijaona Randrianarivelojosia, Martha Lemnge, Sasithon Pukrittayakamee, Richard James Maude, Pascal Ringwald, Celine I Mandara, Abdelrahim Osman Mohamed, Toshihiro Mita, Jaqui Montgomery, Julian C Rayner, David Saunders, Olugbenga A Mokuolu, Lastenia Ruiz, Kathryn Murie, Peter Siba, Collins Misita Morang’a, Alex Shayo, Tuyen Nguyen Thi Kim, Thang Ngo Duc, Vincent Ntui-Njock Ntui, Colin Sutherland, Hong Nguyen Van, Xin-zhuan Su, Marie A Onyamboko, Livingstone Tavul, Irene Omedo, Richard Pearson, Antoinette Tshefu, Wellington Aghoghovwia Oyibo, Vandana Thathy, Chris Drakeley, Huynh Hong Quang, Joseph Vinetz, Christopher V Plowe, Federica Verra, Eduard Rovira-Vallbona, Jason Wendler, Anna Rosanas-Urgell, Teun Bousema, Thuy Nguyen, Mahamadou S. Sissoko, Valentin Ruano-Rubio, Alexis Nzila, Shannon Takala-Harrison, Christen Smith, William Yavo, Ngo Viet Thanh, Arthur Talman, Georgia Whitton, Mahamoudou Toure, Rob W van der Pluijm, Sarah Auburn, Antoine Claessens, Mahamadou Diakite, Kesinee Chotivanich, Mehul Dhorda, Olivo Miotto, Mallika Imwong, Mayfong Mayxay, Alfred Amambua-Ngwa, Philip Bejon, Elizabeth Ashley, Alyssa Barry, Rick M. Fairhurst, Ye Htut, Tran Tinh Hien, Kimberly J Johnson, Dominic P Kwiatkowski, Umberto D'Alessandro, Chanthap Lon, Paul N Newton, Aung P Phyo, Ric N Price, Victoria J Simpson, Kevin Marsh, Nicholas J White, Thomas E Wellems, Lynette Isabella Ochola-Oyier, Mozam Ali, Ambroise Ahouidi, Jacob Almagro-Garcia, Ben Andagalu, Lucas Amenga-Etego, Voahangy Andrianaranjaka, Tobias Apinjoh, Vito Baraka, Hampate Ba, Steffen Borrmann, Oralee Branch, Thanat Chookajorn, Souleymane Dama, Chanaki Amaratunga, Alister Craig, Brigitte Denis, Eleanor Drury, Christiane Dolecek, Patrick Duffy, Berhanu Erko, Abdul Faiz, Muzamil Mahdi Abdel Hamid, Anita Ghansah, and Dionicia Gamboa
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malaria ,plasmodium falciparum ,genomics ,data resource ,genomic epidemiology ,eng ,Medicine ,Science - Abstract
We describe the MalariaGEN Pf7 data resource, the seventh release of Plasmodium falciparum genome variation data from the MalariaGEN network. It comprises over 20,000 samples from 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented. For the first time we include dried blood spot samples that were sequenced after selective whole genome amplification, necessitating new methods to genotype copy number variations. We identify a large number of newly emerging crt mutations in parts of Southeast Asia, and show examples of heterogeneities in patterns of drug resistance within Africa and within the Indian subcontinent. We describe the profile of variations in the C-terminal of the csp gene and relate this to the sequence used in the RTS,S and R21 malaria vaccines. Pf7 provides high-quality data on genotype calls for 6 million SNPs and short indels, analysis of large deletions that cause failure of rapid diagnostic tests, and systematic characterisation of six major drug resistance loci, all of which can be freely downloaded from the MalariaGEN website.
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- 2023
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4. Artemisinin resistance in the malaria parasite, Plasmodium falciparum, originates from its initial transcriptional response
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Lei Zhu, Rob W. van der Pluijm, Michal Kucharski, Sourav Nayak, Jaishree Tripathi, Nicholas J. White, Nicholas P. J. Day, Abul Faiz, Aung Pyae Phyo, Chanaki Amaratunga, Dysoley Lek, Elizabeth A. Ashley, François Nosten, Frank Smithuis, Hagai Ginsburg, Lorenz von Seidlein, Khin Lin, Mallika Imwong, Kesinee Chotivanich, Mayfong Mayxay, Mehul Dhorda, Hoang Chau Nguyen, Thuy Nhien Thanh Nguyen, Olivo Miotto, Paul N. Newton, Podjanee Jittamala, Rupam Tripura, Sasithon Pukrittayakamee, Thomas J. Peto, Tran Tinh Hien, Arjen M. Dondorp, and Zbynek Bozdech
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Biology (General) ,QH301-705.5 - Abstract
Transcriptomic analysis of isolates from the malaria parasite (Plasmodium falciparum) in the Greater Mekong Subregion of Southeast Asia identifies gene expression patterns that are correlated with resistance to a common anti-malaria drug, artemisinin.
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- 2022
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5. 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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6. Clustering of malaria in households in the Greater Mekong Subregion: operational implications for reactive case detection
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Mavuto Mukaka, Pimnara Peerawaranun, Daniel M. Parker, Ladda Kajeechiwa, Francois H. Nosten, Thuy-Nhien Nguyen, Tran Tinh Hien, Rupam Tripura, Thomas J. Peto, Koukeo Phommasone, Mayfong Mayxay, Paul N. Newton, Mallika Imwong, Nicholas P. J. Day, Arjen M. Dondorp, Nicholas J. White, and Lorenz von Seidlein
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Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Malaria reactive case detection is the testing and, if positive, treatment of close contacts of index cases. It is included in national malaria control programmes of countries in the Greater Mekong Subregion to accelerate malaria elimination. Yet the value of reactive case detection in the control and elimination of malaria remains controversial because of the low yield, limited evidence for impact, and high demands on resources. Methods Data from the epidemiological assessments of large mass drug administration (MDA) studies in Myanmar, Vietnam, Cambodia and Laos were analysed to explore malaria infection clustering in households. The proportion of malaria positive cases among contacts screened in a hypothetical reactive case detection programme was then determined. The parasite density thresholds for rapid diagnostic test (RDT) detection was assumed to be > 50/µL (50,000/mL), for dried-blood-spot (DBS) based PCR > 5/µL (5000/mL), and for ultrasensitive PCR (uPCR) with a validated limit of detection at 0.0022/µL (22/mL). Results At baseline, before MDA, 1223 Plasmodium infections were detected by uPCR in 693 households. There was clustering of Plasmodium infections. In 637 households with asymptomatic infections 44% (278/637) had more than one member with Plasmodium infections. In the 132 households with symptomatic infections, 65% (86/132) had more than one member with Plasmodium infections. At baseline 4% of households had more than one Plasmodium falciparum infection, but three months after MDA no household had more than one P. falciparum infected member. Reactive case detection using DBS PCR would have detected ten additional cases in six households, and an RDT screen would have detected five additional cases in three households among the 169 households with at least one RDT positive case. This translates to 19 and 9 additional cases identified per 1000 people screened, respectively. Overall, assuming all febrile RDT positive patients would seek treatment and provoke reactive case detection using RDTs, then 1047 of 1052 (99.5%) Plasmodium infections in these communities would have remained undetected. Conclusion Reactive case detection in the Greater Mekong subregion is predicted to have a negligible impact on the malaria burden, but it has substantial costs in terms of human and financial resources.
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- 2021
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7. An open dataset of Plasmodium vivax genome variation in 1,895 worldwide samples [version 1; peer review: 2 approved]
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Sonia Goncalves, Lemu Golassa, Wasif Khan, Sisay Alemu, Mohammad Shafiul Alam, Pharath Lim, Elizabeth Ashley, Nicholas M Anstey, Bridget E Barber, Jutta Marfurt, Ashenafi Assefa, Dhelio Batista Pereira, Alyssa Barry, Nguyen Hoang Chau, Jun Cao, Fe Espino, Cindy Chu, Ivo Mueller, María Fernanda Villegas, Rick Fairhurst, Thuy-Nhien Nguyen, Yaghoob Hamedi, Matthew J Grigg, Rintis Noviyanti, Ye Htut, Tran Tinh Hien, Nadira Karunaweera, Kimberly J Johnson, Dominic P Kwiatkowski, Srivicha Krudsood, Francois Nosten, Benedikt Ley, Marcus Lacerda, Alejandro Llanos-Cuentas, Yaobao Liu, Tatiana Lopera-Mesa, Milijaona Randrianarivelojosia, Chanthap Lon, Sasithon Pukrittayakamee, Rezika Mohammed, Pascal Michon, Paul N Newton, Chayadol Namaik-larp, Richard D Pearson, Julian C Rayner, Zuleima Pava, Aung P Phyo, Beyene Petros, Awab Ghulam Rahim, Ric N Price, Sasha V Siegel, Angela Rumaseb, Kamala Thriemer, Victoria J Simpson, Marcelo Urbano Ferreira, Alberto Tobon-Castano, Sonam Wangchuk, Ivan D Vélez, Nicholas J White, Thomas E Wellems, Maria F Yasnot, Arjen M. Dondorp, Timothy William, Daniel Yilma, Sarah Auburn, Hidayat Trimarsanto, Abraham Aseffa, Qi Gao, Roberto Amato, Voahangy Andrianaranjaka, Ishag Adam, Kesinee Chotivanich, Olivo Miotto, Chanaki Amaratunga, Eleanor Drury, Diego F. Echeverry, Berhanu Erko, and Abdul Faiz
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malaria ,plasmodium vivax ,genomics ,data resource ,genomic epidemiology ,eng ,Medicine ,Science - Abstract
This report describes the MalariaGEN Pv4 dataset, a new release of curated genome variation data on 1,895 samples of Plasmodium vivax collected at 88 worldwide locations between 2001 and 2017. It includes 1,370 new samples contributed by MalariaGEN and VivaxGEN partner studies in addition to previously published samples from these and other sources. We provide genotype calls at over 4.5 million variable positions including over 3 million single nucleotide polymorphisms (SNPs), as well as short indels and tandem duplications. This enlarged dataset highlights major compartments of parasite population structure, with clear differentiation between Africa, Latin America, Oceania, Western Asia and different parts of Southeast Asia. Each sample has been classified for drug resistance to sulfadoxine, pyrimethamine and mefloquine based on known markers at the dhfr, dhps and mdr1 loci. The prevalence of all of these resistance markers was much higher in Southeast Asia and Oceania than elsewhere. This open resource of analysis-ready genome variation data from the MalariaGEN and VivaxGEN networks is driven by our collective goal to advance research into the complex biology of P. vivax and to accelerate genomic surveillance for malaria control and elimination.
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- 2022
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8. Anti-Gametocyte Antigen Humoral Immunity and Gametocytemia During Treatment of Uncomplicated Falciparum Malaria: A Multi-National Study
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Katherine O’Flaherty, Jo-Anne Chan, Julia C. Cutts, Sophie G. Zaloumis, Elizabeth A. Ashley, Aung Pyae Phyo, Damien R. Drew, Arjen M. Dondorp, Nicholas P. Day, Mehul Dhorda, Rick M. Fairhurst, Pharath Lim, Chanaki Amaratunga, Sasithon Pukrittayakamee, Tran Tinh Hien, Ye Htut, Mayfong Mayxay, M. Abul Faiz, Olugbenga A. Mokuolu, Marie A. Onyamboko, Caterina Fanello, Eizo Takashima, Takafumi Tsuboi, Michael Theisen, Francois Nosten, James G. Beeson, Julie A. Simpson, Nicholas J. White, and Freya J. I. Fowkes
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malaria ,gametocyte ,antibodies ,falciparum malaria ,clinical malaria ,epidemiogy ,Microbiology ,QR1-502 - Abstract
IntroductionUnderstanding the human immune response to Plasmodium falciparum gametocytes and its association with gametocytemia is essential for understanding the transmission of malaria as well as progressing transmission blocking vaccine candidates.MethodsIn a multi-national clinical efficacy trial of artemisinin therapies (13 sites of varying transmission over South-East Asia and Africa), we measured Immunoglobulin G (IgG) responses to recombinant P. falciparum gametocyte antigens expressed on the gametocyte plasma membrane and leading transmission blocking vaccine candidates Pfs230 (Pfs230c and Pfs230D1M) and Pfs48/45 at enrolment in 1,114 participants with clinical falciparum malaria. Mixed effects linear and logistic regression were used to determine the association between gametocyte measures (gametocytemia and gametocyte density) and antibody outcomes at enrolment.ResultsMicroscopy detectable gametocytemia was observed in 11% (127/1,114) of participants at enrolment, and an additional 9% (95/1,114) over the follow-up period (up to day 42) (total 20% of participants [222/1,114]). IgG levels in response to Pfs230c, Pfs48/45 and Pfs230D1M varied across study sites at enrolment (p < 0.001), as did IgG seroprevalence for anti-Pfs230c and D1M IgG (p < 0.001), but not for anti-Pfs48/45 IgG (p = 0.159). In adjusted analyses, microscopy detectable gametocytemia at enrolment was associated with an increase in the odds of IgG seropositivity to the three gametocyte antigens (Pfs230c OR [95% CI], p: 1.70 [1.10, 2.62], 0.017; Pfs48/45: 1.45 [0.85, 2.46], 0.174; Pfs230D1M: 1.70 [1.03, 2.80], 0.037), as was higher gametocyte density at enrolment (per two-fold change in gametocyte density Pfs230c OR [95% CI], p: 1.09 [1.02, 1.17], 0.008; Pfs48/45: 1.05 [0.98, 1.13], 0.185; Pfs230D1M: 1.07 [0.99, 1.14], 0.071).ConclusionPfs230 and Pfs48/45 antibodies are naturally immunogenic targets associated with patent gametocytemia and increasing gametocyte density across multiple malaria endemic settings, including regions with emerging artemisinin-resistant P. falciparum.
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- 2022
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9. Superspreading Event of SARS-CoV-2 Infection at a Bar, Ho Chi Minh City, Vietnam
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Nguyen Van Vinh Chau, Nguyen Thi Thu Hong, Nghiem My Ngoc, Tran Tan Thanh, Phan Nguyen Quoc Khanh, Lam Anh Nguyet, Le Nguyen Truc Nhu, Nguyen Thi Han Ny, Dinh Nguyen Huy Man, Vu Thi Ty Hang, Nguyen Thanh Phong, Nguyen Thi Hong Que, Pham Thi Tuyen, Tran Nguyen Hoang Tu, Tran Tinh Hien, Ngo Ngoc Quang Minh, Le Manh Hung, Nguyen Thanh Truong, Lam Minh Yen, H. Rogier van Doorn, Nguyen Thanh Dung, Guy Thwaites, Nguyen Tri Dung, and Le Van Tan
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COVID-19 ,disease cluster ,pandemic ,reverse transcription PCR ,SARS-CoV-2 ,superspreading ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
We report a superspreading event of severe acute respiratory syndrome coronavirus 2 infection initiated at a bar in Vietnam with evidence of symptomatic and asymptomatic transmission, based on ministry of health reports, patient interviews, and whole-genome sequence analysis. Crowds in enclosed indoor settings with poor ventilation may be considered at high risk for transmission.
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- 2021
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10. Detecting geospatial patterns of Plasmodium falciparum parasite migration in Cambodia using optimized estimated effective migration surfaces
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Yao Li, Amol C. Shetty, Chanthap Lon, Michele Spring, David L. Saunders, Mark M. Fukuda, Tran Tinh Hien, Sasithon Pukrittayakamee, Rick M. Fairhurst, Arjen M. Dondorp, Christopher V. Plowe, Timothy D. O’Connor, Shannon Takala-Harrison, and Kathleen Stewart
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Plasmodium falciparum ,Estimated effective migration surfaces ,Parasite migration ,Malaria elimination ,Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
Abstract Background Understanding the genetic structure of natural populations provides insight into the demographic and adaptive processes that have affected those populations. Such information, particularly when integrated with geospatial data, can have translational applications for a variety of fields, including public health. Estimated effective migration surfaces (EEMS) is an approach that allows visualization of the spatial patterns in genomic data to understand population structure and migration. In this study, we developed a workflow to optimize the resolution of spatial grids used to generate EEMS migration maps and applied this optimized workflow to estimate migration of Plasmodium falciparum in Cambodia and bordering regions of Thailand and Vietnam. Methods The optimal density of EEMS grids was determined based on a new workflow created using density clustering to define genomic clusters and the spatial distance between genomic clusters. Topological skeletons were used to capture the spatial distribution for each genomic cluster and to determine the EEMS grid density; i.e., both genomic and spatial clustering were used to guide the optimization of EEMS grids. Model accuracy for migration estimates using the optimized workflow was tested and compared to grid resolutions selected without the optimized workflow. As a test case, the optimized workflow was applied to genomic data generated from P. falciparum sampled in Cambodia and bordering regions, and migration maps were compared to estimates of malaria endemicity, as well as geographic properties of the study area, as a means of validating observed migration patterns. Results Optimized grids displayed both high model accuracy and reduced computing time compared to grid densities selected in an unguided manner. In addition, EEMS migration maps generated for P. falciparum using the optimized grid corresponded to estimates of malaria endemicity and geographic properties of the study region that might be expected to impact malaria parasite migration, supporting the validity of the observed migration patterns. Conclusions Optimized grids reduce spatial uncertainty in the EEMS contours that can result from user-defined parameters, such as the resolution of the spatial grid used in the model. This workflow will be useful to a broad range of EEMS users as it can be applied to analyses involving other organisms of interest and geographic areas.
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- 2020
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11. Intracluster correlation coefficients in the Greater Mekong Subregion for sample size calculations of cluster randomized malaria trials
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Pimnara Peerawaranun, Jordi Landier, Francois H. Nosten, Thuy-Nhien Nguyen, Tran Tinh Hien, Rupam Tripura, Thomas J. Peto, Koukeo Phommasone, Mayfong Mayxay, Nicholas P. J. Day, Arjen Dondorp, Nick White, Lorenz von Seidlein, and Mavuto Mukaka
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ICC ,Malaria ,Prevalence ,Incidence ,Cluster randomized trial ,Sample size ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Sample size calculations for cluster randomized trials are a recognized methodological challenge for malaria research in pre-elimination settings. Positively correlated responses from the participants in the same cluster are a key feature in the estimated sample size required for a cluster randomized trial. The degree of correlation is measured by the intracluster correlation coefficient (ICC) where a higher coefficient suggests a closer correlation hence less heterogeneity within clusters but more heterogeneity between clusters. Methods Data on uPCR-detected Plasmodium falciparum and Plasmodium vivax infections from a recent cluster randomized trial which aimed at interrupting malaria transmission through mass drug administrations were used to calculate the ICCs for prevalence and incidence of Plasmodium infections. The trial was conducted in four countries in the Greater Mekong Subregion, Laos, Myanmar, Vietnam and Cambodia. Exact and simulation approaches were used to estimate ICC values for both the prevalence and the incidence of parasitaemia. In addition, the latent variable approach to estimate ICCs for the prevalence was utilized. Results The ICCs for prevalence ranged between 0.001 and 0.082 for all countries. The ICC from the combined 16 villages in the Greater Mekong Subregion were 0.26 and 0.21 for P. falciparum and P. vivax respectively. The ICCs for incidence of parasitaemia ranged between 0.002 and 0.075 for Myanmar, Cambodia and Vietnam. There were very high ICCs for incidence in the range of 0.701 to 0.806 in Laos during follow-up. Conclusion ICC estimates can help researchers when designing malaria cluster randomized trials. A high variability in ICCs and hence sample size requirements between study sites was observed. Realistic sample size estimates for cluster randomized malaria trials in the Greater Mekong Subregion have to assume high between cluster heterogeneity and ICCs. This work focused on uPCR-detected infections; there remains a need to develop more ICC references for trials designed around prevalence and incidence of clinical outcomes. Adequately powered trials are critical to estimate the benefit of interventions to malaria in a reliable and reproducible fashion. Trial registration: ClinicalTrials.govNCT01872702. Registered 7 June 2013. Retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT01872702
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- 2019
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12. The probability of a sequential Plasmodium vivax infection following asymptomatic Plasmodium falciparum and P. vivax infections in Myanmar, Vietnam, Cambodia, and Laos
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Lorenz von Seidlein, Pimnara Peerawaranun, Mavuto Mukaka, Francois H. Nosten, Thuy-Nhien Nguyen, Tran Tinh Hien, Rupam Tripura, Thomas J. Peto, Tiengkham Pongvongsa, Koukeo Phommasone, Mayfong Mayxay, Mallika Imwong, James Watson, Sasithon Pukrittayakamee, Nicholas P. J. Day, and Arjen M. Dondorp
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P. falciparum ,P. vivax ,Primaquine ,Radical cure ,Universal ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Adding 8-aminoquinoline to the treatment of falciparum, in addition to vivax malaria, in locations where infections with both species are prevalent could prevent vivax reactivation. The potential risk of haemolysis under a universal radical cure policy using 8-aminoquinoline needs to be weighed against the benefit of preventing repeated vivax episodes. Estimating the frequency of sequential Plasmodium vivax infections following either falciparum or vivax malaria episodes is needed for such an assessment. Methods Quarterly surveillance data collected during a mass drug administration trial in the Greater Mekong Subregion in 2013–17 was used to estimate the probability of asymptomatic sequential infections by the same and different Plasmodium species. Asymptomatic Plasmodium infections were detected by high-volume ultrasensitive qPCR. Quarterly surveys of asymptomatic Plasmodium prevalence were used to estimate the probability of a P. vivax infection following Plasmodium falciparum and P. vivax infections. Results 16,959 valid sequential paired test results were available for analysis. Of these, 534 (3%) had an initial P. falciparum monoinfection, 1169 (7%) a P. vivax monoinfection, 217 (1%) had mixed (P. falciparum + P. vivax) infections, and 15,039 (89%) had no Plasmodium detected in the initial survey. Participants who had no evidence of a Plasmodium infection had a 4% probability to be found infected with P. vivax during the subsequent survey. Following an asymptomatic P. falciparum monoinfection participants had a 9% probability of having a subsequent P. vivax infection (RR 2.4; 95% CI 1.8 to 3.2). Following an asymptomatic P. vivax monoinfection, the participants had a 45% probability of having a subsequent P. vivax infection. The radical cure of 12 asymptomatic P. falciparum monoinfections would have prevented one subsequent P. vivax infection, whereas treatment of 2 P. vivax monoinfections may suffice to prevent one P. vivax relapse. Conclusion Universal radical cure could play a role in the elimination of vivax malaria. The decision whether to implement universal radical cure for P. falciparum as well as for P. vivax depends on the prevalence of P. falciparum and P. vivax infections, the prevalence and severity of G6PD deficiency in the population and the feasibility to administer 8-aminoquinoline regimens safely. Trial registration ClinicalTrials.gov Identifier: NCT01872702, first posted June 7th 2013, https://clinicaltrials.gov/ct2/show/NCT01872702. This study was registered with ClinicalTrials.gov under NCT02802813 on 16th June 2016. https://clinicaltrials.gov/ct2/show/NCT02802813
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- 2019
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13. Provider and household costs of Plasmodium vivax malaria episodes: a multicountry comparative analysis of primary trial data/Cout des episodes de paludisme a Plasmodium vivax pour les menages et les prestataires: une analyse comparative multipays de donnees d'essais primaries/Costos del proveedor y del hogar de los episodios de malaria por Plasmodium vivax: un analisis comparativo multinacional de los datos del ensayo primario
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Devine, Angela, Pasaribu, Ayodhia P., Teferi, Tedlla, Pham, Huong-Thu, Awab, Ghulam Rahim, Contantia, Febrina, Nguyen, Thuy-Nhien, Ngo, Viet-Thanh, Tran, Tinh-Hien, Hailu, Asrat, Gilchrist, Kim, Green, Justin A., Koh, Gavin C.K.W., Thriemer, Kamala, Taylor, Walter R.J., Day, Nicholas P.J., Price, Ric N., and Lubell, Yoel
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Cost benefit analysis -- Economic aspects -- Comparative analysis -- Surveys -- Health aspects ,Health care costs -- Health aspects -- Surveys -- Comparative analysis -- Economic aspects ,Phosphates -- Product development ,Disease eradication -- Comparative analysis -- Surveys -- Health aspects -- Economic aspects ,Health care industry -- Product development ,Infection -- Economic aspects -- Surveys -- Health aspects -- Comparative analysis ,Malaria -- Surveys -- Health aspects -- Economic aspects -- Comparative analysis ,Health care industry ,Cost benefit analysis ,Health ,World Health Organization -- Surveys - Abstract
Objective To determine household and health-care provider costs associated with Plasmodium vivax infection across a range of endemic settings. Methods We collected cost data alongside three multicentre clinical trials of P vivax treatment in Afghanistan, Brazil, Colombia, Ethiopia, Indonesia, Philippines, Peru, Thailand and Viet Nam conducted between April 2014 to December 2017. We derived household costs from trial participant surveys administered at enrolment and again 2 weeks later to determine the costs of treatment and transportation, and the number of days that patients and their household caregivers were unable to undertake their usual activities. We determined costs of routine care by health-care providers by micro-costing the resources used to diagnose and treat P vivax at the study sites. Findings The mean total household costs ranged from 8.7 United States dollars (US$; standard deviation, SD: 4.3) in Afghanistan to US$ 254.7 (SD: 148.4) in Colombia. Across all countries, productivity losses were the largest household cost component, resulting in mean indirect costs ranging from US$ 5.3 (SD: 3.0) to US$ 220.8 (SD: 158.40). The range of health-care provider costs for routine care was US$ 3.6-6.6. The cost of administering a glucose-6-phosphate-dehydrogenase rapid diagnostic test, ranged from US$ 0.9 to 13.5, consistently lower than the costs of the widely-used fluorescent spot test (US$ 6.3 to 17.4). Conclusion An episode of P vivax malaria results in high costs to households. The costs of diagnosing and treating P vivax are important inputs for future cost-effectiveness analyses to ensure optimal allocation of resources for malaria elimination. Objectif Determiner les couts, pour les menages et les prestataires de soins, associes a l'infection par Plasmodium vivax dans differentes zones endemiques. Methodes Nous avons recueilli des donnees sur les couts a l'occasion de trois essais cliniques multicentres relatifs au traitement contre P vivax menes en Afghanistan, au Bresil, en Colombie, en Ethiopie, en Indonesie, aux Philippines, au Perou, en Thailande et au Viet Nam entre avril 2014 et decembre 2017. Nous avons calcule les couts pour les menages a partir d'enquetes realisees aupres des participants aux essais, lors de leur admission puis 2 semaines plus tard, afin de determiner les couts de traitement et de transport ainsi que le nombre de jours ou les patients et leurs aidants familiaux n'avaient pu accomplir leurs activites habituelles. Nous avons determine le cout des soins courants par les prestataires de soins en calculant le cout individuel des ressources utilisees pour diagnostiquer et traiter P vivax sur le site des etudes. Resultats Les couts totaux moyens pour les menages allaient de 8.7 dollars des Etats-Unis ($ US; ecart type, ET: 4,3) en Afghanistan a 254.7 $ US (ET: 148,4) en Colombie. Tous pays confondus, les pertes de productivity etaient la principale composante des couts pour les menages, puisqu'elles entrainaient des couts indirects moyens allant de 5,3 $ US (ET: 3,0) a 220,8 $ US (ET: 158,40). En ce qui concerne les prestataires de soins, le cout des soins courants allait de 3,6 a 6,6 $ US. Le cout de realisation d'un test de diagnostic rapide base sur le glucose6- phosphate-deshydrogenase variait de 0,9 $ US a 13,5 $ US, un cout toujours inferieur a celui du tres repandu test par fluorescence (6,3 $ US a 17,4 $ US). Conclusion Un episode de paludisme a P vivax entraine des couts eleves pour les menages. Connaitre les couts du diagnostic et du traitement de P vivax sera fort utile aux futures analyses cout-efficacite. Cela permettra d'affecter les ressources de maniere optimale en vue d'eradiquer le paludisme. Objetivo Determinar los costos del hogar y de los proveedores de atencion de la salud asociados con la infeccion por Plasmodium vivax en una variedad de ambitos endemicos. Metodos Se recopilaron datos de costos junto con tres ensayos clinicos multicentricos del tratamiento con P. vivax en Afganistan, Brasil, Colombia, Etiopia, Filipinas, Indonesia, Peru, Tailandia y Vietnam realizados entre abril de 2014 y diciembre de 2017. Los costos del hogar se derivaron de las encuestas de los participantes del ensayo administradas en el momento de la inscripcion y de nuevo dos semanas despues para determinar los costos del tratamiento y del transporte, asi como el numero de dias en que los pacientes y los cuidadores en el hogar no pudieron llevar a cabo sus actividades habituales. Se determinaron los costos de la atencion de rutina por parte de los proveedores de atencion de la salud mediante el microcosto de los recursos utilizados para diagnosticar y tratar el P. vivax en los centros de estudio. Resultados Los costos totales promedio de los hogares oscilaron entre 8,7 dolares estadounidenses (USD; desviacion estandar, DE: 4,3) en Afganistan y 254,7 USD (DE: 148,4) en Colombia. En todos los paises, las perdidas de productividad fueron el mayor componente del costo del hogar, lo que dio lugar a costos indirectos promedios que oscilaron entre 5,3 y 220,8 USD. El rango de los costos de los proveedores de atencion de la salud para la atencion de rutina fue de 3,6 a 6,6 USD. El costo por administrar una prueba de diagnostico rapido de la glucosa-6- fosfatodeshidrogenasa, vario de 0,9 a 13,5 USD, consistentemente mas bajo que los costos de la prueba de fluorescencia aleatoria ampliamente utilizada (6,3 a 17,4 USD). Conclusion Un episodio de malaria por P. vivax tiene como resultado un alto costo para el hogar. Los costos del diagnostico y tratamiento de P. vivax son insumos importantes para futuros analisis de costoefectividad que aseguren una asignacion optima de recursos para la eliminacion de la malaria., Introduction Outside Sub-Saharan Africa, Plasmodium vivax is now the predominant cause of malaria, affecting 14.0 million patients in 2016. (1) While cost-effectiveness analyses can inform the efficient provision of health-care [...]
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- 2019
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14. Genetic surveillance in the Greater Mekong subregion and South Asia to support malaria control and elimination
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Christopher G Jacob, Nguyen Thuy-Nhien, Mayfong Mayxay, Richard J Maude, Huynh Hong Quang, Bouasy Hongvanthong, Viengxay Vanisaveth, Thang Ngo Duc, Huy Rekol, Rob van der Pluijm, Lorenz von Seidlein, Rick Fairhurst, François Nosten, Md Amir Hossain, Naomi Park, Scott Goodwin, Pascal Ringwald, Keobouphaphone Chindavongsa, Paul Newton, Elizabeth Ashley, Sonexay Phalivong, Rapeephan Maude, Rithea Leang, Cheah Huch, Le Thanh Dong, Kim-Tuyen Nguyen, Tran Minh Nhat, Tran Tinh Hien, Hoa Nguyen, Nicole Zdrojewski, Sara Canavati, Abdullah Abu Sayeed, Didar Uddin, Caroline Buckee, Caterina I Fanello, Marie Onyamboko, Thomas Peto, Rupam Tripura, Chanaki Amaratunga, Aung Myint Thu, Gilles Delmas, Jordi Landier, Daniel M Parker, Nguyen Hoang Chau, Dysoley Lek, Seila Suon, James Callery, Podjanee Jittamala, Borimas Hanboonkunupakarn, Sasithon Pukrittayakamee, Aung Pyae Phyo, Frank Smithuis, Khin Lin, Myo Thant, Tin Maung Hlaing, Parthasarathi Satpathi, Sanghamitra Satpathi, Prativa K Behera, Amar Tripura, Subrata Baidya, Neena Valecha, Anupkumar R Anvikar, Akhter Ul Islam, Abul Faiz, Chanon Kunasol, Eleanor Drury, Mihir Kekre, Mozam Ali, Katie Love, Shavanthi Rajatileka, Anna E Jeffreys, Kate Rowlands, Christina S Hubbart, Mehul Dhorda, Ranitha Vongpromek, Namfon Kotanan, Phrutsamon Wongnak, Jacob Almagro Garcia, Richard D Pearson, Cristina V Ariani, Thanat Chookajorn, Cinzia Malangone, T Nguyen, Jim Stalker, Ben Jeffery, Jonathan Keatley, Kimberly J Johnson, Dawn Muddyman, Xin Hui S Chan, John Sillitoe, Roberto Amato, Victoria Simpson, Sonia Gonçalves, Kirk Rockett, Nicholas P Day, Arjen M Dondorp, Dominic P Kwiatkowski, and Olivo Miotto
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malaria ,genetic surveillance ,drug resistance ,asia ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Background: National 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. Methods: Samples 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. Results: GenRe-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. Conclusions: GenRe-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. Funding: The 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
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15. An open dataset of Plasmodium falciparum genome variation in 7,000 worldwide samples [version 2; peer review: 2 approved]
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MalariaGEN, Ambroise Ahouidi, Mozam Ali, Jacob Almagro-Garcia, Alfred Amambua-Ngwa, Chanaki Amaratunga, Roberto Amato, Lucas Amenga-Etego, Ben Andagalu, Tim J. C. Anderson, Voahangy Andrianaranjaka, Tobias Apinjoh, Cristina Ariani, Elizabeth A Ashley, Sarah Auburn, Gordon A. Awandare, Hampate Ba, Vito Baraka, Alyssa E. Barry, Philip Bejon, Gwladys I. Bertin, Maciej F. Boni, Steffen Borrmann, Teun Bousema, Oralee Branch, Peter C. Bull, George B. J. Busby, Thanat Chookajorn, Kesinee Chotivanich, Antoine Claessens, David Conway, Alister Craig, Umberto D'Alessandro, Souleymane Dama, Nicholas PJ Day, Brigitte Denis, Mahamadou Diakite, Abdoulaye Djimdé, Christiane Dolecek, Arjen M Dondorp, Chris Drakeley, Eleanor Drury, Patrick Duffy, Diego F. Echeverry, Thomas G. Egwang, Berhanu Erko, Rick M. Fairhurst, Abdul Faiz, Caterina A. Fanello, Mark M. Fukuda, Dionicia Gamboa, Anita Ghansah, Lemu Golassa, Sonia Goncalves, William L. Hamilton, G. L. Abby Harrison, Lee Hart, Christa Henrichs, Tran Tinh Hien, Catherine A. Hill, Abraham Hodgson, Christina Hubbart, Mallika Imwong, Deus S. Ishengoma, Scott A. Jackson, Chris G. Jacob, Ben Jeffery, Anna E. Jeffreys, Kimberly J. Johnson, Dushyanth Jyothi, Claire Kamaliddin, Edwin Kamau, Mihir Kekre, Krzysztof Kluczynski, Theerarat Kochakarn, Abibatou Konaté, Dominic P. Kwiatkowski, Myat Phone Kyaw, Pharath Lim, Chanthap Lon, Kovana M. Loua, Oumou Maïga-Ascofaré, Cinzia Malangone, Magnus Manske, Jutta Marfurt, Kevin Marsh, Mayfong Mayxay, Alistair Miles, Olivo Miotto, Victor Mobegi, Olugbenga A. Mokuolu, Jacqui Montgomery, Ivo Mueller, Paul N. Newton, Thuy Nguyen, Thuy-Nhien Nguyen, Harald Noedl, Francois Nosten, Rintis Noviyanti, Alexis Nzila, Lynette I. Ochola-Oyier, Harold Ocholla, Abraham Oduro, Irene Omedo, Marie A. Onyamboko, Jean-Bosco Ouedraogo, Kolapo Oyebola, Richard D. Pearson, Norbert Peshu, Aung Pyae Phyo, Chris V. Plowe, Ric N. Price, Sasithon Pukrittayakamee, Milijaona Randrianarivelojosia, Julian C. Rayner, Pascal Ringwald, Kirk A. Rockett, Katherine Rowlands, Lastenia Ruiz, David Saunders, Alex Shayo, Peter Siba, Victoria J. Simpson, Jim Stalker, Xin-zhuan Su, Colin Sutherland, Shannon Takala-Harrison, Livingstone Tavul, Vandana Thathy, Antoinette Tshefu, Federica Verra, Joseph Vinetz, Thomas E. Wellems, Jason Wendler, Nicholas J. White, Ian Wright, William Yavo, and Htut Ye
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Medicine ,Science - Abstract
MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.
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- 2021
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16. A validation study of microscopy versus quantitative PCR for measuring Plasmodium falciparum parasitemia
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Emma Ballard, Claire Y. T. Wang, Tran Tinh Hien, Nguyen Thanh Tong, Louise Marquart, Zuleima Pava, Joel Tarning, Peter O’Rourke, and James S. McCarthy
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Microscopy ,qPCR ,Plasmodium falciparum ,Validation ,Arctic medicine. Tropical medicine ,RC955-962 - Abstract
Abstract Microscopy and 18S qPCR are the most common and field-friendly methods for quantifying malaria parasite density, and it is important that these methods can be interpreted as giving equivalent results. We compared results of quantitative measurement of Plasmodium falciparum parasitemia by microscopy and by 18S qPCR in a phase 2a study. Microscopy positive samples (n = 355; median 810 parasites/μL [IQR 40–10,471]) showed close agreement with 18S qPCR in mean log10/mL transformed parasitemia values by paired t test (difference 0.04, 95%CI − 0.01–0.10, p = 0.088). Excellent intraclass correlation (0.97) and no evidence of systematic or proportional differences by Passing–Bablok regression were observed. 18S qPCR appears to give equivalent parasitemia values to microscopy, which indicates 18S qPCR is an appropriate alternative method to quantify parasitemia in clinical trials.
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- 2019
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17. Molecular characterization and mapping of glucose-6-phosphate dehydrogenase (G6PD) mutations in the Greater Mekong Subregion
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Germana Bancone, Didier Menard, Nimol Khim, Saorin Kim, Lydie Canier, Chea Nguong, Koukeo Phommasone, Mayfong Mayxay, Sabine Dittrich, Malavanh Vongsouvath, Nadine Fievet, Jean-Yves Le Hesran, Valerie Briand, Sommay Keomany, Paul N. Newton, Gornpan Gorsawun, Kaelan Tardy, Cindy S. Chu, Orpreeya Rattanapalroj, Le Thanh Dong, Huynh Hong Quang, Nguyen Tam-Uyen, Nguyen Thuy-Nhien, Tran Tinh Hien, Michael Kalnoky, and Francois Nosten
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Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Plasmodium vivax malaria elimination can only be achieved by the deployment of 8-aminoquinolines (primaquine and tafenoquine) in combination with ACT to kill both blood and liver-stage parasites. However, primaquine and the other 8-aminoquinolines cause dose-dependent haemolysis in subjects with G6PD deficiency, an X-linked disorder of red blood cells that is very common in populations living in tropical and subtropical areas. In order to inform safer use of 8-aminoquinolines in the Greater Mekong Subregion, a multi-centre study was carried out to assess the prevalence of G6PD deficiency and to identify the main G6PD variants in samples collected in Cambodia, Lao PDR, Myanmar, Thailand and Vietnam. Methods Blood samples were collected in the five countries during National Malaria Surveys or during Population Surveys. During Population Surveys samples were characterized for G6PD phenotype using the Fluorescent Spot Test. Samples were then genotyped for a panel of G6PD mutations. Results G6PD deficiency was found to be common in the region with an overall mean prevalence of deficient or mutated hemizygous males of 14.0%, ranging from a mean 7.3% in Thailand, 8.1% in Lao PDR, 8.9% in Vietnam, 15.8% in Myanmar and 18.8% in Cambodia. Mahidol and Viangchan mutations were the most common and widespread variants found among the nine investigated. Conclusions Owing to the high prevalence of G6PD deficiency in the Greater Mekong Subregion, strategies for vivax malaria elimination should include point-of-care G6PD testing (both qualitative and quantitative) to allow safe and wide treatment with 8-aminoquinolines.
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- 2019
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18. An open dataset of Plasmodium falciparum genome variation in 7,000 worldwide samples [version 1; peer review: 2 approved]
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MalariaGEN, Ambroise Ahouidi, Mozam Ali, Jacob Almagro-Garcia, Alfred Amambua-Ngwa, Chanaki Amaratunga, Roberto Amato, Lucas Amenga-Etego, Ben Andagalu, Tim J. C. Anderson, Voahangy Andrianaranjaka, Tobias Apinjoh, Cristina Ariani, Elizabeth A. Ashley, Sarah Auburn, Gordon Awandare, Hampate Ba, Vito Baraka, Alyssa E. Barry, Philip Bejon, Gwladys I. Bertin, Maciej F. Boni, Steffen Borrmann, Teun Bousema, Oralee Branch, Peter C. Bull, George B. J. Busby, Thanat Chookajorn, Kesinee Chotivanich, Antoine Claessens, David Conway, Alister Craig, Umberto D'Alessandro, Souleymane Dama, Nicholas PJ Day, Brigitte Denis, Mahamadou Diakite, Abdoulaye Djimdé, Christiane Dolecek, Arjen M Dondorp, Chris Drakeley, Eleanor Drury, Patrick Duffy, Diego F. Echeverry, Thomas G. Egwang, Berhanu Erko, Rick M. Fairhurst, Abdul Faiz, Caterina A. Fanello, Mark M. Fukuda, Dionicia Gamboa, Anita Ghansah, Lemu Golassa, Sonia Goncalves, William L. Hamilton, G. L. Abby Harrison, Lee Hart, Christa Henrichs, Tran Tinh Hien, Catherine A. Hill, Abraham Hodgson, Christina Hubbart, Mallika Imwong, Deus S. Ishengoma, Scott A. Jackson, Chris G. Jacob, Ben Jeffery, Anna E. Jeffreys, Kimberly J. Johnson, Dushyanth Jyothi, Claire Kamaliddin, Edwin Kamau, Mihir Kekre, Krzysztof Kluczynski, Theerarat Kochakarn, Abibatou Konaté, Dominic P. Kwiatkowski, Myat Phone Kyaw, Pharath Lim, Chanthap Lon, Kovana M. Loua, Oumou Maïga-Ascofaré, Cinzia Malangone, Magnus Manske, Jutta Marfurt, Kevin Marsh, Mayfong Mayxay, Alistair Miles, Olivo Miotto, Victor Mobegi, Olugbenga A. Mokuolu, Jacqui Montgomery, Ivo Mueller, Paul N. Newton, Thuy Nguyen, Thuy-Nhien Nguyen, Harald Noedl, Francois Nosten, Rintis Noviyanti, Alexis Nzila, Lynette I. Ochola-Oyier, Harold Ocholla, Abraham Oduro, Irene Omedo, Marie A. Onyamboko, Jean-Bosco Ouedraogo, Kolapo Oyebola, Richard D. Pearson, Norbert Peshu, Aung Pyae Phyo, Chris V. Plowe, Ric N. Price, Sasithon Pukrittayakamee, Milijaona Randrianarivelojosia, Julian C. Rayner, Pascal Ringwald, Kirk A. Rockett, Katherine Rowlands, Lastenia Ruiz, David Saunders, Alex Shayo, Peter Siba, Victoria J. Simpson, Jim Stalker, Xin-zhuan Su, Colin Sutherland, Shannon Takala-Harrison, Livingstone Tavul, Vandana Thathy, Antoinette Tshefu, Federica Verra, Joseph Vinetz, Thomas E. Wellems, Jason Wendler, Nicholas J. White, Ian Wright, William Yavo, and Htut Ye
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Medicine ,Science - Abstract
MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.
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- 2021
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19. Mass drug administrations with dihydroartemisinin-piperaquine and single low dose primaquine to eliminate Plasmodium falciparum have only a transient impact on Plasmodium vivax: Findings from randomised controlled trials.
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Koukeo Phommasone, Frank van Leth, Thomas J Peto, Jordi Landier, Thuy-Nhien Nguyen, Rupam Tripura, Tiengkham Pongvongsa, Khin Maung Lwin, Ladda Kajeechiwa, May Myo Thwin, Daniel M Parker, Jacher Wiladphaingern, Suphak Nosten, Stephane Proux, Chea Nguon, Chan Davoeung, Huy Rekol, Bipin Adhikari, Cholrawee Promnarate, Kesinee Chotivanich, Borimas Hanboonkunupakarn, Podjanee Jittmala, Phaik Yeong Cheah, Mehul Dhorda, Mallika Imwong, Mavuto Mukaka, Pimnara Peerawaranun, Sasithon Pukrittayakamee, Paul N Newton, Guy E Thwaites, Nicholas P J Day, Mayfong Mayxay, Tran Tinh Hien, Francois H Nosten, Frank Cobelens, Arjen M Dondorp, Nicholas J White, and Lorenz von Seidlein
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Medicine ,Science - Abstract
BackgroundMass administrations of antimalarial drugs (MDA) have reduced the incidence and prevalence of P. falciparum infections in a trial in the Greater Mekong Subregion. Here we assess the impact of the MDA on P. vivax infections.MethodsBetween May 2013 and July 2017, four villages in each Myanmar, Vietnam, Cambodia and Lao PDR were selected based on high prevalence of P. falciparum infections. Eight of the 16 villages were randomly assigned to receive MDA consisting of three-monthly rounds of three-day courses of dihydroartemisinin-piperaquine and, except in Cambodia, a single low-dose of primaquine. Cross-sectional surveys were conducted at quarterly intervals to detect Plasmodium infections using ultrasensitive qPCR. The difference in the cumulative incidence between the groups was assessed through a discrete time survival approach, the difference in prevalence through a difference-in-difference analysis, and the difference in the number of participants with a recurrence of P. vivax infection through a mixed-effect logistic regression.Results3,790 (86%) residents in the intervention villages participated in at least one MDA round, of whom 2,520 (57%) participated in three rounds. The prevalence of P. vivax infections fell from 9.31% to 0.89% at month 3 but rebounded by six months to 5.81%. There was no evidence that the intervention reduced the cumulative incidence of P.vivax infections (95% confidence interval [CI] Odds ratio (OR): 0.29 to 1.36). Similarly, there was no evidence of MDA related reduction in the number of participants with at least one recurrent infection (OR: 0.34; 95% CI: 0.08 to 1.42).ConclusionMDA with schizontocidal drugs had a lasting effect on P. falciparum infections but only a transient effect on the prevalence of P. vivax infections. Radical cure with an 8-aminoquinoline will be needed for the rapid elimination of vivax malaria.
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- 2020
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20. The decline of malaria in Vietnam, 1991–2014
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Sandra M. Goldlust, Phung Duc Thuan, Dang Duy Hoang Giang, Ngo Duc Thang, Guy E. Thwaites, Jeremy Farrar, Ngo Viet Thanh, Tran Dang Nguyen, Bryan T. Grenfell, Maciej F. Boni, and Tran Tinh Hien
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Malaria ,Artemisinin ,Vietnam ,Vector control ,Urbanization ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Despite the well-documented clinical efficacy of artemisinin-based combination therapy (ACT) against malaria, the population-level effects of ACT have not been studied thoroughly until recently. An ideal case study for these population-level effects can be found in Vietnam’s gradual adoption of artemisinin in the 1990s. Methods and results Analysis of Vietnam’s national annual malaria reports (1991–2014) revealed that a 10% increase in artemisinin procurement corresponded to a 32.8% (95% CI 27.7–37.5%) decline in estimated malaria cases. There was no consistent national or regional effect of vector control on malaria. The association between urbanization and malaria was generally negative and sometimes statistically significant. Conclusions The decline of malaria in Vietnam can largely be attributed to the adoption of artemisinin-based case management. Recent analyses from Africa showed that insecticide-treated nets had the greatest effect on lowering malaria prevalence, suggesting that the success of interventions is region-specific. Continuing malaria elimination efforts should focus on both vector control and increased access to ACT.
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- 2018
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21. The prevalence, incidence and prevention of Plasmodium falciparum infections in forest rangers in Bu Gia Map National Park, Binh Phuoc province, Vietnam: a pilot study
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Do Hung Son, Nguyen Thuy-Nhien, Lorenz von Seidlein, Truong Le Phuc-Nhi, Ngo Thi Phu, Nguyen Thi Kim Tuyen, Nguyen Huyen Tran, Nguyen Van Dung, Bui Van Quan, Nicholas P. J. Day, Arjen M. Dondorp, Nicholas J. White, Guy E. Thwaites, and Tran Tinh Hien
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Plasmodium falciparum ,Plasmodium vivax ,An. dirus ,An. maculatus ,An. barbirostris ,Anti-malarial resistance ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Prophylaxis for high-risk populations, such as forest workers, could be one component for malaria elimination in the Greater Mekong Sub-region. A study was conducted to assess the malaria incidence in forest rangers and the feasibility of malaria prophylaxis for rangers sleeping in forest camps. Methods Forest rangers deployed in the Bu Gia Map National Park, Vietnam were invited to participate in the study. Plasmodium infections were cleared using presumptive treatment, irrespective of malaria status, with a 3-day course dihydroartemisinin/piperaquine (DP) and a 14-day course of primaquine. Before returning to the forest, study participants were randomly allocated to a 3-day course of DP or placebo. Fifteen days after returning from their forest deployment the participants were tested for Plasmodium infections using uPCR. Results Prior to treatment, 30 of 150 study participants (20%) were found to be infected with Plasmodium. Seventeen days (median) after enrolment the rangers were randomized to DP or placebo 2 days before returning to forest camps where they stayed between 2 and 20 days (median 9.5 days). One ranger in the DP-prophylaxis arm and one in the placebo arm were found to be infected with Plasmodium falciparum 15 days (median) after returning from the forest. The evaluable P. falciparum isolates had molecular markers indicating resistance to artemisinins (K13-C580Y) and piperaquine (plasmepsin), but none had multiple copies of pfmdr1 associated with mefloquine resistance. Conclusion Anti-malarial prophylaxis in forest rangers is feasible. The findings of the study highlight the threat of multidrug-resistant malaria. Trial registration NCT02788864
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- 2017
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22. The impact of targeted malaria elimination with mass drug administrations on falciparum malaria in Southeast Asia: A cluster randomised trial.
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Lorenz von Seidlein, Thomas J Peto, Jordi Landier, Thuy-Nhien Nguyen, Rupam Tripura, Koukeo Phommasone, Tiengkham Pongvongsa, Khin Maung Lwin, Lilly Keereecharoen, Ladda Kajeechiwa, May Myo Thwin, Daniel M Parker, Jacher Wiladphaingern, Suphak Nosten, Stephane Proux, Vincent Corbel, Nguyen Tuong-Vy, Truong Le Phuc-Nhi, Do Hung Son, Pham Nguyen Huong-Thu, Nguyen Thi Kim Tuyen, Nguyen Thanh Tien, Le Thanh Dong, Dao Van Hue, Huynh Hong Quang, Chea Nguon, Chan Davoeung, Huy Rekol, Bipin Adhikari, Gisela Henriques, Panom Phongmany, Preyanan Suangkanarat, Atthanee Jeeyapant, Benchawan Vihokhern, Rob W van der Pluijm, Yoel Lubell, Lisa J White, Ricardo Aguas, Cholrawee Promnarate, Pasathorn Sirithiranont, Benoit Malleret, Laurent Rénia, Carl Onsjö, Xin Hui Chan, Jeremy Chalk, Olivo Miotto, Krittaya Patumrat, Kesinee Chotivanich, Borimas Hanboonkunupakarn, Podjanee Jittmala, Nils Kaehler, Phaik Yeong Cheah, Christopher Pell, Mehul Dhorda, Mallika Imwong, Georges Snounou, Mavuto Mukaka, Pimnara Peerawaranun, Sue J Lee, Julie A Simpson, Sasithon Pukrittayakamee, Pratap Singhasivanon, Martin P Grobusch, Frank Cobelens, Frank Smithuis, Paul N Newton, Guy E Thwaites, Nicholas P J Day, Mayfong Mayxay, Tran Tinh Hien, Francois H Nosten, Arjen M Dondorp, and Nicholas J White
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Medicine - Abstract
BackgroundThe emergence and spread of multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion (GMS) threatens global malaria elimination efforts. Mass drug administration (MDA), the presumptive antimalarial treatment of an entire population to clear the subclinical parasite reservoir, is a strategy to accelerate malaria elimination. We report a cluster randomised trial to assess the effectiveness of dihydroartemisinin-piperaquine (DP) MDA in reducing falciparum malaria incidence and prevalence in 16 remote village populations in Myanmar, Vietnam, Cambodia, and the Lao People's Democratic Republic, where artemisinin resistance is prevalent.Methods and findingsAfter establishing vector control and community-based case management and following intensive community engagement, we used restricted randomisation within village pairs to select 8 villages to receive early DP MDA and 8 villages as controls for 12 months, after which the control villages received deferred DP MDA. The MDA comprised 3 monthly rounds of 3 daily doses of DP and, except in Cambodia, a single low dose of primaquine. We conducted exhaustive cross-sectional surveys of the entire population of each village at quarterly intervals using ultrasensitive quantitative PCR to detect Plasmodium infections. The study was conducted between May 2013 and July 2017. The investigators randomised 16 villages that had a total of 8,445 residents at the start of the study. Of these 8,445 residents, 4,135 (49%) residents living in 8 villages, plus an additional 288 newcomers to the villages, were randomised to receive early MDA; 3,790 out of the 4,423 (86%) participated in at least 1 MDA round, and 2,520 out of the 4,423 (57%) participated in all 3 rounds. The primary outcome, P. falciparum prevalence by month 3 (M3), fell by 92% (from 5.1% [171/3,340] to 0.4% [12/2,828]) in early MDA villages and by 29% (from 7.2% [246/3,405] to 5.1% [155/3,057]) in control villages. Over the following 9 months, the P. falciparum prevalence increased to 3.3% (96/2,881) in early MDA villages and to 6.1% (128/2,101) in control villages (adjusted incidence rate ratio 0.41 [95% CI 0.20 to 0.84]; p = 0.015). Individual protection was proportional to the number of completed MDA rounds. Of 221 participants with subclinical P. falciparum infections who participated in MDA and could be followed up, 207 (94%) cleared their infections, including 9 of 10 with artemisinin- and piperaquine-resistant infections. The DP MDAs were well tolerated; 6 severe adverse events were detected during the follow-up period, but none was attributable to the intervention.ConclusionsAdded to community-based basic malaria control measures, 3 monthly rounds of DP MDA reduced the incidence and prevalence of falciparum malaria over a 1-year period in areas affected by artemisinin resistance. P. falciparum infections returned during the follow-up period as the remaining infections spread and malaria was reintroduced from surrounding areas. Limitations of this study include a relatively small sample of villages, heterogeneity between villages, and mobility of villagers that may have limited the impact of the intervention. These results suggest that, if used as part of a comprehensive, well-organised, and well-resourced elimination programme, DP MDA can be a useful additional tool to accelerate malaria elimination.Trial registrationClinicalTrials.gov NCT01872702.
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- 2019
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23. Community engagement, social context and coverage of mass anti-malarial administration: Comparative findings from multi-site research in the Greater Mekong sub-Region.
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Christopher L Pell, Bipin Adhikari, May Myo Thwin, Ladda Kajeechiwa, Suphak Nosten, Francois H Nosten, Kate M Sahan, Frank M Smithuis, Thuy-Nhien Nguyen, Tran Tinh Hien, Rupam Tripura, Thomas J Peto, Nou Sanann, Chea Nguon, Tiengkham Pongvongsa, Koukeo Phommasone, Mayfong Mayxay, Mavuto Mukaka, Pimnara Peerawaranun, Nils Kaehler, Phaik Yeong Cheah, Nicholas P J Day, Nicholas J White, Arjen M Dondorp, and Lorenz von Seidlein
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Medicine ,Science - Abstract
BACKGROUND:Between 2013 and 2017, targeted malaria elimination (TME), a package of interventions that includes mass drug administration (MDA)-was piloted in communities with reservoirs of asymptomatic P. falciparum across the Greater Mekong sub-Region (GMS). Coverage in target communities is a key determinant of the effectiveness of MDA. Drawing on mixed methods research conducted alongside TME pilot studies, this article examines the impact of the community engagement, local social context and study design on MDA coverage. METHODS AND FINDINGS:Qualitative and quantitative data were collected using questionnaire-based surveys, semi-structured and in-depth interviews, focus group discussions, informal conversations, and observations of study activities. Over 1500 respondents were interviewed in Myanmar, Vietnam, Cambodia and Laos. Interview topics included attitudes to malaria and experiences of MDA. Overall coverage of mass anti-malarial administration was high, particularly participation in at least a single round (85%). Familiarity with and concern about malaria prompted participation in MDA; as did awareness of MDA and familiarity with the aim of eliminating malaria. Fear of adverse events and blood draws discouraged people. Hence, community engagement activities sought to address these concerns but their impact was mediated by the trust relationships that study staff could engender in communities. In contexts of weak healthcare infrastructure and (cash) poverty, communities valued the study's ancillary care and the financial compensation. However, coverage did not necessarily decrease in the absence of cash compensation. Community dynamics, affected by politics, village conformity, and household decision-making also affected coverage. CONCLUSIONS:The experimental nature of TME presented particular challenges to achieving high coverage. Nonetheless, the findings reflect those from studies of MDA under implementation conditions and offer useful guidance for potential regional roll-out of MDA: it is key to understand target communities and provide appropriate information in tailored ways, using community engagement that engenders trust.
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- 2019
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24. Intrathecal Immunoglobulin for treatment of adult patients with tetanus: A randomized controlled 2x2 factorial trial [version 2; referees: 2 approved]
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Huỳnh Thị Loan, Lam Minh Yen, Evelyne Kestelyn:, Nguyen Van Hao, Tran Tan Thanh, Nguyen Thi Phuong Dung, Hugo C. Turner, Ronald B. Geskus, Marcel Wolbers, Le Van Tan, H. Rogier Van Doorn, Nicholas P. Day, Duncan Wyncoll, Tran Tinh Hien, Guy E. Thwaites, Nguyen Van Vinh Chau, and C. Louise Thwaites
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Medicine ,Science - Abstract
Despite long-standing availability of an effective vaccine, tetanus remains a significant problem in many countries. Outcome depends on access to mechanical ventilation and intensive care facilities and in settings where these are limited, mortality remains high. Administration of tetanus antitoxin by the intramuscular route is recommended treatment for tetanus, but as the tetanus toxin acts within the central nervous system, it has been suggested that intrathecal administration of antitoxin may be beneficial. Previous studies have indicated benefit, but with the exception of one small trial no blinded studies have been performed. The objective of this study is to establish whether the addition of intrathecal tetanus antitoxin reduces the need for mechanical ventilation in patients with tetanus. Secondary objectives: to determine whether the addition of intrathecal tetanus antitoxin reduces autonomic nervous system dysfunction and length of hospital/ intensive care unit stay; whether the addition of intrathecal tetanus antitoxin in the treatment of tetanus is safe and cost-effective; to provide data to inform recommendation of human rather than equine antitoxin. This study will enroll adult patients (≥16 years old) with tetanus admitted to the Hospital for Tropical Diseases, Ho Chi Minh City. The study is a 2x2 factorial blinded randomized controlled trial. Eligible patients will be randomized in a 1:1:1:1 manner to the four treatment arms (intrathecal treatment and human intramuscular treatment, intrathecal treatment and equine intramuscular treatment, sham procedure and human intramuscular treatment, sham procedure and equine intramuscular treatment). Primary outcome measure will be requirement for mechanical ventilation. Secondary outcome measures: duration of hospital/ intensive care unit stay, duration of mechanical ventilation, in-hospital and 240-day mortality and disability, new antibiotic prescription, incidence of ventilator associated pneumonia and autonomic nervous system dysfunction, total dose of benzodiazepines and pipecuronium, and incidence of adverse events. Trial registration: ClinicalTrials.gov NCT02999815 Registration date: 21 December 2016
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- 2018
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25. Lineage-informative microhaplotypes for spatio-temporal surveillance of Plasmodium vivax malaria parasites
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Sasha V. Siegel, Roberto Amato, Hidayat Trimarsanto, Edwin Sutanto, Mariana Kleinecke, Kathryn Murie, Georgia Whitton, Aimee R. Taylor, James A. Watson, Mallika Imwong, Ashenafi Assefa, Awab Ghulam Rahim, Nguyen Hoang Chau, Tran Tinh Hien, Justin A Green, Gavin Koh, Nicholas J. White, Nicholas Day, Dominic P. Kwiatkowski, Julian C. Rayner, Ric N. Price, and Sarah Auburn
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Article - Abstract
Challenges in understanding the origin of recurrentPlasmodium vivaxinfections constrains the surveillance of antimalarial efficacy and transmission of this neglected parasite. Recurrent infections within an individual may arise from activation of dormant liver stages (relapse), blood-stage treatment failure (recrudescence) or new inoculations (reinfection). Molecular inference of familial relatedness (identity-by-descent or IBD) based on whole genome sequence data, together with analysis of the intervals between parasitaemic episodes (“time-to-event” analysis), can help resolve the probable origin of recurrences. Whole genome sequencing of predominantly low-densityP. vivaxinfections is challenging, so an accurate and scalable genotyping method to determine the origins of recurrent parasitaemia would be of significant benefit. We have developed aP. vivaxgenome-wide informatics pipeline to select specific microhaplotype panels that can capture IBD within small, amplifiable segments of the genome. Using a global set of 615P. vivaxgenomes, we derived a panel of 100 microhaplotypes, each comprising 3-10 high frequency SNPs within HE= 0.70-0.81) and it captured 89% (273/307) of the polyclonal infections detected with genome-wide datasets. Using data simulations, we demonstrate lower error in estimating pairwise IBD using microhaplotypes, relative to traditional biallelic SNP barcodes. Our panel exhibited high accuracy in predicting the country of origin (median Matthew’s correlation coefficient >0.9 in 90% countries tested) and it also captured local infection outbreak and bottlenecking events. The informatics pipeline is available open-source and yields microhaplotypes that can be readily transferred to high-throughput amplicon sequencing assays for surveillance in malaria-endemic regions.
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- 2023
26. The impact of environmental and climatic variation on the spatiotemporal trends of hospitalized pediatric diarrhea in Ho Chi Minh City, Vietnam
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Thompson, Corinne N., Zelner, Jonathan L., Nhu, Tran Do Hoang, Phan, My VT, Hoang Le, Phuc, Nguyen Thanh, Hung, Vu Thuy, Duong, Minh Nguyen, Ngoc, Ha Manh, Tuan, Van Hoang Minh, Tu, Lu Lan, Vi, Nguyen Van Vinh, Chau, Tran Tinh, Hien, von Clemm, Emmiliese, Storch, Harry, Thwaites, Guy, Grenfell, Bryan T., and Baker, Stephen
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- 2015
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27. Adjunctive dexamethasone for the treatment of HIV-infected adults with tuberculous meningitis (ACT HIV): Study protocol for a randomised controlled trial [version 2; referees: 1 approved, 2 approved with reservations]
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Joseph Donovan, Nguyen Hoan Phu, Nguyen Thi Hoang Mai, Le Tien Dung, Darma Imran, Erlina Burhan, Lam Hong Bao Ngoc, Nguyen Duc Bang, Do Chau Giang, Dang Thi Minh Ha, Jeremy Day, Le Thi Phuong Thao, Nguyen TT Thuong, Nguyen Nang Vien, Ronald B. Geskus, Marcel Wolbers, Raph L Hamers, Reinout van Crevel, Mugi Nursaya, Kartika Maharani, Tran Tinh Hien, Kevin Baird, Nguyen Huu Lan, Evelyne Kestelyn, Nguyen Van Vinh Chau, and Guy E. Thwaites
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Medicine ,Science - Abstract
Background: Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Co-infection with HIV increases the risk of developing TBM, complicates treatment, and substantially worsens outcome. Whether corticosteroids confer a survival benefit in HIV-infected patients with TBM remains uncertain. Hepatitis is the most common drug-induced serious adverse event associated with anti-tuberculosis treatment, occurring in 20% of HIV-infected patients. The suggested concentration thresholds for stopping anti-tuberculosis drugs are not evidence-based. This study aims to determine whether dexamethasone is a safe and effective addition to the first 6-8 weeks of anti-tuberculosis treatment of TBM in patients with HIV, and investigate alternative management strategies in a subset of patients who develop drug induced liver injury (DILI) that will enable the safe continuation of rifampicin and isoniazid therapy. Methods: We will perform a parallel group, randomised (1:1), double blind, placebo-controlled multi-centre Phase III trial, comparing the effect of dexamethasone versus placebo on overall survival in HIV-infected patients with TBM, in addition to standard anti-tuberculosis and antiretroviral treatment. The trial will be set in two hospitals in Ho Chi Minh City, Vietnam, and two hospitals in Jakarta, Indonesia. The trial will enrol 520 HIV-infected adults. An ancillary study will perform a randomised comparison of three DILI management strategies with the aim of demonstrating which strategy results in the least interruption in rifampicin and isoniazid treatment. An identical ancillary study will also be performed in the linked randomised controlled trial of dexamethasone in HIV-uninfected adults with TBM stratified by LTA4H genotype (LAST ACT). Discussion: Whether corticosteroids confer a survival benefit in HIV-infected patients remains uncertain, and the current evidence base for using corticosteroids in this context is limited. Interruptions in anti-tuberculosis chemotherapy is a risk factor for death from TBM. Alternative management strategies in DILI may allow the safe continuation of rifampicin and isoniazid therapy.
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- 2018
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28. Evaluation of the Luminex xTAG Respiratory Viral Panel FAST v2 assay for detection of multiple respiratory viral pathogens in nasal and throat swabs in Vietnam [version 2; referees: 2 approved]
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Vu Thi Ty Hang, Nguyen Thi Han Ny, Tran My Phuc, Pham Thi Thanh Tam, Dang Thao Huong, Ho Dang Trung Nghia, Nguyen Tran Anh Vu, Pham Thi Hong Phuong, Nguyen Van Xang, Nguyen Dong, Pham Nhu Hiep, Nguyen Van Hung, Tran Tinh Hien, Maia Rabaa, Guy E. Thwaites, Stephen Baker, Le Van Tan, H.Rogier van Doorn, and VIZIONS consortium
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Methods for Diagnostic & Therapeutic Studies ,Virology ,Medicine ,Science - Abstract
Background: Acute respiratory infections (ARI) are among the leading causes of hospitalization in children ≤5 years old. Rapid diagnostics of viral pathogens is essential to avoid unnecessary antibiotic treatment, thereby slowing down antibiotic-resistance. We evaluated the diagnostic performance of the Luminex xTAG Respiratory Viral Panel FAST v2 against viral specific PCR as reference assays for ARI in Vietnam. Methods: Four hundred and forty two nose and throat swabs were collected in viral transport medium, and were tested with Luminex xTAG Respiratory Viral Panel FAST v2. Multiplex RT-PCR and single RT-PCR were used as references. Results: Overall, sensitivity of the Luminex against reference assays was 91.8%, 95% CI 88.1-94.7 (270/294), whilst 112/6336 (1.8%, 95% CI, 1.4-2.1) of pathogens were detected by the Luminex, but not by reference assays. Frequency of pathogens detected by Luminex and reference assays was 379 and 292, respectively. The diagnostic yield was 66.7% (295/442, 95%CI 62.1-71.1%) for the Luminex assay and 54.1% (239/442, 95% CI, 49.3-58.8%) for reference assays. The Luminex kit had higher yields for all viruses except influenza B virus, respiratory syncytial virus, and human bocavirus. High agreements between both methods [mean (range): 0.91 (0.83-1.00)] were found for 10/15 viral agents. Conclusions: The Luminex assay is a high throughput multiplex platform for rapid detection of common viral pathogens causing ARI. Although the current high cost may prevent Luminex assays from being widely used, especially in limited resource settings where ARI are felt most, its introduction in clinical diagnostics may help reduce unnecessary use of antibiotic prescription.
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- 2018
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29. Adjunctive dexamethasone for the treatment of HIV-uninfected adults with tuberculous meningitis stratified by Leukotriene A4 hydrolase genotype (LAST ACT): Study protocol for a randomised double blind placebo controlled non-inferiority trial [version 1; referees: 2 approved]
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Joseph Donovan, Nguyen Hoan Phu, Le Thi Phuong Thao, Nguyen Huu Lan, Nguyen Thi Hoang Mai, Nguyen Thi Mai Trang, Nguyen Thi Thu Hiep, Tran Bao Nhu, Bui Thi Bich Hanh, Vu Thi Phuong Mai, Nguyen Duc Bang, Do Chau Giang, Dang Thi Minh Ha, Jeremy Day, Nguyen TT Thuong, Nguyen Nang Vien, Ronald B. Geskus, Tran Tinh Hien, Evelyne Kestelyn, Marcel Wolbers, Nguyen Van Vinh Chau, and Guy E. Thwaites
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Medicine ,Science - Abstract
Background: Tuberculosis kills more people than any other bacterial infection worldwide. In tuberculous meningitis (TBM), a common functional promoter variant (C/T transition) in the gene encoding leukotriene A4 hydrolase (LTA4H), predicts pre-treatment inflammatory phenotype and response to dexamethasone in HIV-uninfected individuals. The primary aim of this study is to determine whether LTA4H genotype determines benefit or harm from adjunctive dexamethasone in HIV-uninfected Vietnamese adults with TBM. The secondary aim is to investigate alternative management strategies in individuals who develop drug induced liver injury (DILI) that will enable the safe continuation of rifampicin and isoniazid therapy. Methods: We will perform a parallel group, randomised (1:1), double blind, placebo-controlled, multi-centre Phase III non-inferiority trial, comparing dexamethasone versus placebo for 6-8 weeks in addition to standard anti-tuberculosis treatment in HIV-uninfected patients with TBM stratified by LTA4H genotype. The primary endpoint will be death or new neurological event. The trial will enrol approximately 720 HIV-uninfected adults with a clinical diagnosis of TBM, from two hospitals in Ho Chi Minh City, Vietnam. 640 participants with CC or CT- LTA4H genotype will be randomised to either dexamethasone or placebo, and the remaining TT- genotype participants will be treated with standard-of-care dexamethasone. We will also perform a randomised comparison of three management strategies for anti-tuberculosis DILI. An identical ancillary study will also be perfomed in the linked randomised controlled trial of dexamethasone in HIV-infected adults with TBM (ACT HIV). Discussion: Previous data have shown that LTA4H genotype may be a critical determinant of inflammation and consequently of adjunctive anti-inflammatory treatment response in TBM. We will stratify dexamethasone therapy according to LTA4H genotype in HIV-uninfected adults, which may indicate a role for targeted anti-inflammatory therapy according to variation in LTA4H C/T transition. A comparison of DILI management strategies may allow the safe continuation of rifampicin and isoniazid.
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- 2018
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30. Evaluation of the Luminex xTAG Respiratory Viral Panel FAST v2 assay for detection of multiple respiratory viral pathogens in nasal and throat swabs in Vietnam [version 1; referees: 2 approved]
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Vu Thi Ty Hang, Nguyen Thi Han Ny, Tran My Phuc, Pham Thi Thanh Tam, Dang Thao Huong, Ho Dang Trung Nghia, Nguyen Tran Anh Vu, Pham Thi Hong Phuong, Nguyen Van Xang, Nguyen Dong, Pham Nhu Hiep, Nguyen Van Hung, Tran Tinh Hien, Maia Rabaa, Guy E. Thwaites, Stephen Baker, Le Van Tan, H.Rogier van Doorn, and VIZIONS consortium
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Methods for Diagnostic & Therapeutic Studies ,Virology ,Medicine ,Science - Abstract
Background: Acute respiratory infections (ARI) are among the leading causes of hospitalization in children ≤5 years old. Rapid diagnostics of viral pathogens is essential to avoid unnecessary antibiotic treatment, thereby slowing down antibiotic-resistance. We evaluated the diagnostic performance of the Luminex xTAG Respiratory Viral Panel FAST v2 against viral specific PCR as reference assays for ARI in Vietnam. Methods: Four hundred and forty two nose and throat swabs were collected in viral transport medium, and were tested with Luminex xTAG Respiratory Viral Panel FAST v2. Multiplex RT-PCR and single RT-PCR were used as references. Results: Overall, viral pathogens were detected in a total count of 270/294 (91.8%, 95% CI 88.1-94.7) by the Luminex among reference assays, whilst 112/6336 (1.8%, 95% CI, 1.4-2.1) of pathogens were detected by the Luminex, but not by reference assays. Frequency of pathogens detected by Luminex and reference assays was 379 and 292, respectively. The diagnostic yield was 66.7% (295/442, 95%CI 62.1-71.1%) for the Luminex assay and 54.1% (239/442, 95% CI, 49.3-58.8%) for reference assays. The Luminex kit had higher yields for all viruses except influenza B virus, respiratory syncytial virus, and human bocavirus. High agreements between both methods [mean (range): 0.91 (0.83-1.00)] were found for 10/15 viral agents. Conclusions: The Luminex assay is a high throughput multiplex platform for rapid detection of common viral pathogens causing ARI. Although the current high cost may prevent Luminex assays from being widely used, especially in limited resource settings where ARI are felt most, its introduction in clinical diagnostics may help reduce unnecessary use of antibiotic prescription.
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- 2017
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31. Defining Surrogate Endpoints for Clinical Trials in Severe Falciparum Malaria.
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Atthanee Jeeyapant, Hugh W Kingston, Katherine Plewes, Richard J Maude, Josh Hanson, M Trent Herdman, Stije J Leopold, Thatsanun Ngernseng, Prakaykaew Charunwatthana, Nguyen Hoan Phu, Aniruddha Ghose, M Mahtab Uddin Hasan, Caterina I Fanello, Md Abul Faiz, Tran Tinh Hien, Nicholas P J Day, Nicholas J White, and Arjen M Dondorp
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Medicine ,Science - Abstract
Clinical trials in severe falciparum malaria require a large sample size to detect clinically meaningful differences in mortality. This means few interventions can be evaluated at any time. Using a validated surrogate endpoint for mortality would provide a useful alternative allowing a smaller sample size. Here we evaluate changes in coma score and plasma lactate as surrogate endpoints for mortality in severe falciparum malaria.Three datasets of clinical studies in severe malaria were re-evaluated: studies from Chittagong, Bangladesh (adults), the African 'AQUAMAT' trial comparing artesunate and quinine (children), and the Vietnamese 'AQ' study (adults) comparing artemether with quinine. The absolute change, relative change, slope of the normalization over time, and time to normalization were derived from sequential measurements of plasma lactate and coma score, and validated for their use as surrogate endpoint, including the proportion of treatment effect on mortality explained (PTE) by these surrogate measures.Improvements in lactate concentration or coma scores over the first 24 hours of admission, were strongly prognostic for survival in all datasets. In hyperlactataemic patients in the AQ study (n = 173), lower mortality with artemether compared to quinine closely correlated with faster reduction in plasma lactate concentration, with a high PTE of the relative change in plasma lactate at 8 and 12 hours of 0.81 and 0.75, respectively. In paediatric patients enrolled in the 'AQUAMAT' study with cerebral malaria (n = 785), mortality was lower with artesunate compared to quinine, but this was not associated with faster coma recovery.The relative changes in plasma lactate concentration assessed at 8 or 12 hours after admission are valid surrogate endpoints for severe malaria studies on antimalarial drugs or adjuvant treatments aiming at improving the microcirculation. Measures of coma recovery are not valid surrogate endpoints for mortality.
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- 2017
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32. Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia
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Geraldine M Clarke, Kirk Rockett, Katja Kivinen, Christina Hubbart, Anna E Jeffreys, Kate Rowlands, Muminatou Jallow, David J Conway, Kalifa A Bojang, Margaret Pinder, Stanley Usen, Fatoumatta Sisay-Joof, Giorgio Sirugo, Ousmane Toure, Mahamadou A Thera, Salimata Konate, Sibiry Sissoko, Amadou Niangaly, Belco Poudiougou, Valentina D Mangano, Edith C Bougouma, Sodiomon B Sirima, David Modiano, Lucas N Amenga-Etego, Anita Ghansah, Kwadwo A Koram, Michael D Wilson, Anthony Enimil, Jennifer Evans, Olukemi K Amodu, Subulade Olaniyan, Tobias Apinjoh, Regina Mugri, Andre Ndi, Carolyne M Ndila, Sophie Uyoga, Alexander Macharia, Norbert Peshu, Thomas N Williams, Alphaxard Manjurano, Nuno Sepúlveda, Taane G Clark, Eleanor Riley, Chris Drakeley, Hugh Reyburn, Vysaul Nyirongo, David Kachala, Malcolm Molyneux, Sarah J Dunstan, Nguyen Hoan Phu, Nguyen Ngoc Quyen, Cao Quang Thai, Tran Tinh Hien, Laurens Manning, Moses Laman, Peter Siba, Harin Karunajeewa, Steve Allen, Angela Allen, Timothy ME Davis, Pascal Michon, Ivo Mueller, Síle F Molloy, Susana Campino, Angeliki Kerasidou, Victoria J Cornelius, Lee Hart, Shivang S Shah, Gavin Band, Chris CA Spencer, Tsiri Agbenyega, Eric Achidi, Ogobara K Doumbo, Jeremy Farrar, Kevin Marsh, Terrie Taylor, Dominic P Kwiatkowski, and MalariaGEN Consortium
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G6PD deficiency ,genetic association ,infectious disease ,selection ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effect has proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual’s level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia. Models of balancing selection based on these findings indicate that an evolutionary trade-off between different clinical outcomes of P. falciparum infection could have been a major cause of the high levels of G6PD polymorphism seen in human populations.
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- 2017
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33. An open dataset of
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Ishag, Adam, Mohammad Shafiul, Alam, Sisay, Alemu, Chanaki, Amaratunga, Roberto, Amato, Voahangy, Andrianaranjaka, Nicholas M, Anstey, Abraham, Aseffa, Elizabeth, Ashley, Ashenafi, Assefa, Sarah, Auburn, Bridget E, Barber, Alyssa, Barry, Dhelio, Batista Pereira, Jun, Cao, Nguyen Hoang, Chau, Kesinee, Chotivanich, Cindy, Chu, Arjen M, Dondorp, Eleanor, Drury, Diego F, Echeverry, Berhanu, Erko, Fe, Espino, Rick, Fairhurst, Abdul, Faiz, María, Fernanda Villegas, Qi, Gao, Lemu, Golassa, Sonia, Goncalves, Matthew J, Grigg, Yaghoob, Hamedi, Tran Tinh, Hien, Ye, Htut, Kimberly J, Johnson, Nadira, Karunaweera, Wasif, Khan, Srivicha, Krudsood, Dominic P, Kwiatkowski, Marcus, Lacerda, Benedikt, Ley, Pharath, Lim, Yaobao, Liu, Alejandro, Llanos-Cuentas, Chanthap, Lon, Tatiana, Lopera-Mesa, Jutta, Marfurt, Pascal, Michon, Olivo, Miotto, Rezika, Mohammed, Ivo, Mueller, Chayadol, Namaik-Larp, Paul N, Newton, Thuy-Nhien, Nguyen, Francois, Nosten, Rintis, Noviyanti, Zuleima, Pava, Richard D, Pearson, Beyene, Petros, Aung P, Phyo, Ric N, Price, Sasithon, Pukrittayakamee, Awab Ghulam, Rahim, Milijaona, Randrianarivelojosia, Julian C, Rayner, Angela, Rumaseb, Sasha V, Siegel, Victoria J, Simpson, Kamala, Thriemer, Alberto, Tobon-Castano, Hidayat, Trimarsanto, Marcelo, Urbano Ferreira, Ivan D, Vélez, Sonam, Wangchuk, Thomas E, Wellems, Nicholas J, White, Timothy, William, Maria F, Yasnot, and Daniel, Yilma
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This report describes the MalariaGEN Pv4 dataset, a new release of curated genome variation data on 1,895 samples of
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- 2022
34. Epidemiology, Clinical Manifestations, and Outcomes of Streptococcus suis Infection in Humans
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Vu Thi Lan Huong, Ngo Ha, Nguyen Tien Huy, Peter Horby, Ho Dang Trung Nghia, Vu Dinh Thiem, Xiaotong Zhu, Ngo Thi Hoa, Tran Tinh Hien, Javier Zamora, Constance Schultsz, Heiman Frank Louis Wertheim, and Kenji Hirayama
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Streptococcus suis ,bacterial meningitis ,systematic review ,meta-analysis ,zoonoses ,bacteria ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
Streptococcus suis, a bacterium that affects pigs, is a neglected pathogen that causes systemic disease in humans. We conducted a systematic review and meta-analysis to summarize global estimates of the epidemiology, clinical characteristics, and outcomes of this zoonosis. We searched main literature databases for all studies through December 2012 using the search term “streptococcus suis.” The prevalence of S. suis infection is highest in Asia; the primary risk factors are occupational exposure and eating of contaminated food. The pooled proportions of case-patients with pig-related occupations and history of eating high-risk food were 38.1% and 37.3%, respectively. The main clinical syndrome was meningitis (pooled rate 68.0%), followed by sepsis, arthritis, endocarditis, and endophthalmitis. The pooled case-fatality rate was 12.8%. Sequelae included hearing loss (39.1%) and vestibular dysfunction (22.7%). Our analysis identified gaps in the literature, particularly in assessing risk factors and sequelae of this infection.
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- 2014
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35. Comparison of Antibody Responses and Parasite Clearance in Artemisinin Therapeutic Efficacy Studies in the Democratic Republic of Congo and Asia
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Julia C Cutts, Katherine O’Flaherty, Sophie G Zaloumis, Elizabeth A Ashley, Jo Anne Chan, Marie A Onyamboko, Caterina Fanello, Arjen M Dondorp, Nicholas P Day, Aung Pyae Phyo, Mehul Dhorda, Mallika Imwong, Rick M Fairhurst, Pharath Lim, Chanaki Amaratunga, Sasithon Pukrittayakamee, Tran Tinh Hien, Ye Htut, Mayfong Mayxay, M Abdul Faiz, Eizo Takashima, Takafumi Tsuboi, James G Beeson, Francois Nosten, Julie A Simpson, Nicholas J White, Freya J I Fowkes, AII - Infectious diseases, and Intensive Care Medicine
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Plasmodium falciparum ,malaria ,Drug Resistance ,Artemisinins ,resistance ,Antimalarials ,Infectious Diseases ,artemisinin ,parasite ,Antibody Formation ,Democratic Republic of the Congo ,antibodies ,Immunology and Allergy ,Animals ,Humans ,Parasites ,Malaria, Falciparum ,Child - Abstract
Background Understanding the effect of immunity on Plasmodium falciparum clearance is essential for interpreting therapeutic efficacy studies designed to monitor emergence of artemisinin drug resistance. In low-transmission areas of Southeast Asia, where resistance has emerged, P. falciparum antibodies confound parasite clearance measures. However, variation in naturally acquired antibodies across Asian and sub-Saharan African epidemiological contexts and their impact on parasite clearance re yet to be quantified. Methods In an artemisinin therapeutic efficacy study, antibodies to 12 pre-erythrocytic and erythrocytic P. falciparum antigens were measured in 118 children with uncomplicated P. falciparum malaria in the Democratic Republic of Congo (DRC) and compared with responses in patients from Asian sites, described elsewhere. Results Parasite clearance half-life was shorter in DRC patients (median, 2 hours) compared with most Asian sites (median, 2–7 hours), but P. falciparum antibody levels and seroprevalences were similar. There was no evidence for an association between antibody seropositivity and parasite clearance half-life (mean difference between seronegative and seropositive, −0.14 to +0.40 hour) in DRC patients. Conclusions In DRC, where artemisinin remains highly effective, the substantially shorter parasite clearance time compared with Asia was not explained by differences in the P. falciparum antibody responses studied.
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- 2022
36. A sensitive real-time PCR for detection and subgrouping of human respiratory syncytial virus
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Do, Lien Anh Ha, van Doorn, H. Rogier, Bryant, Juliet E., Nghiem, My Ngoc, Nguyen Van, Vinh Chau, Vo, Cong Khanh, Nguyen, Minh Dung, Tran, Tinh Hien, Farrar, Jeremy, and de Jong, Menno D.
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- 2012
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37. Enterovirus 71–associated Hand, Foot, and Mouth Disease, Southern Vietnam, 2011
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Truong Huu Khanh, Saraswathy Sabanathan, Tran Tan Thanh, Le Phan Kim Thoa, Tang Chi Thuong, Vu thi Ty Hang, Jeremy Farrar, Tran Tinh Hien, Nguyen van Vinh Chau, and H. Rogier van Doorn
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hand ,foot ,and mouth disease ,Vietnam ,enterovirus 71 ,viruses ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
We prospectively studied 3,791 children hospitalized during 2011 during a large outbreak of enterovirus 71–associated hand, foot, and mouth disease in Vietnam. Formal assessment of public health interventions, use of intravenous immunoglobulin and other therapies, and factors predisposing for progression of disease is needed to improve clinical management.
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- 2012
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38. Pharmacogenetic assessment of tafenoquine efficacy in patients with Plasmodium vivax malaria
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Fe Espino, Chanthap Lon, John J Breton, Marcus V. G. Lacerda, Daniel Yilma, David L. Saunders, Maria F Villegas, Tran Tinh Hien, Pamela L. St. Jean, Srivicha Krudsood, Iván D. Vélez, Gavin C. K. W. Koh, Chayadol S Namaik-Larp, Alejandro Llanos-Cuentas, Stephan Duparc, Justin A. Green, Dhelio Batista Pereira, and Rezika Mohammed
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Male ,0301 basic medicine ,Primaquine ,Tafenoquine ,efficacy ,Plasmodium vivax ,tafenoquine ,030226 pharmacology & pharmacy ,chemistry.chemical_compound ,0302 clinical medicine ,Medicine ,General Pharmacology, Toxicology and Pharmaceutics ,Genetics (clinical) ,pharmacogenetics ,Clinical Trials as Topic ,education.field_of_study ,biology ,Plasmodium vivax malaria ,Middle Aged ,Treatment Outcome ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Aminoquinolines ,Molecular Medicine ,Female ,medicine.drug ,Adult ,medicine.medical_specialty ,Short Communication ,purl.org/pe-repo/ocde/ford#1.06.03 [https] ,Population ,Polymorphism, Single Nucleotide ,Antimalarials ,Young Adult ,03 medical and health sciences ,Internal medicine ,parasitic diseases ,Malaria, Vivax ,Genetics ,Humans ,In patient ,education ,Molecular Biology ,Retrospective Studies ,Chromosomes, Human, Pair 12 ,business.industry ,medicine.disease ,biology.organism_classification ,Pharmacogenomic Testing ,Clinical trial ,030104 developmental biology ,chemistry ,business ,Pharmacogenetics ,Malaria ,Genome-Wide Association Study ,purl.org/pe-repo/ocde/ford#1.06.07 [https] - Abstract
Supplemental Digital Content is available in the text., Plasmodium vivax has the largest geographic range of human malaria species and is challenging to manage and eradicate due to its ability to establish a dormant liver stage, the hypnozoite, which can reactivate leading to relapse. Until recently, the only treatment approved to kill hypnozoites was the 8-aminoquinoline, primaquine, requiring daily treatment for 14 days. Tafenoquine, an 8-aminoquinoline single-dose treatment with activity against P. vivax hypnozoites, has recently been approved by the US Food and Drug Administration and Australian Therapeutic Goods Administration for the radical cure of P. vivax malaria in patients 16 years and older. We conducted an exploratory pharmacogenetic analysis (GSK Study 208099) to assess the role of host genome-wide variation on tafenoquine efficacy in patients with P. vivax malaria using data from three GSK clinical trials, GATHER and DETECTIVE Part 1 and Part 2. Recurrence-free efficacy at 6 and 4 months and time to recurrence up to 6 months postdosing were analyzed in 438 P. vivax malaria patients treated with tafenoquine. Among the approximately 10.6 million host genetic variants analyzed, two signals reached genome-wide significance (P value ≤ 5 × 10−8). rs62103056, and variants in a chromosome 12 intergenic region, were associated with recurrence-free efficacy at 6 and 4 months, respectively. Neither of the signals has an obvious biological rationale and would need replication in an independent population. This is the first genome-wide association study to evaluate genetic influence on response to tafenoquine in P. vivax malaria.
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- 2020
39. 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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Rob W van der Pluijm, Rupam Tripura, Richard M Hoglund, Aung Pyae Phyo, Dysoley Lek, Akhter ul Islam, Anupkumar R Anvikar, Parthasarathi Satpathi, Sanghamitra Satpathi, Prativa Kumari Behera, Amar Tripura, Subrata Baidya, Marie Onyamboko, Nguyen Hoang Chau, Yok Sovann, Seila Suon, Sokunthea Sreng, Sivanna Mao, Savuth Oun, Sovannary Yen, Chanaki Amaratunga, Kitipumi Chutasmit, Chalermpon Saelow, Ratchadaporn Runcharern, Weerayuth Kaewmok, Nhu Thi Hoa, Ngo Viet Thanh, Borimas Hanboonkunupakarn, James J Callery, Akshaya Kumar Mohanty, James Heaton, Myo Thant, Kripasindhu Gantait, Tarapada Ghosh, Roberto Amato, Richard D Pearson, Christopher G Jacob, Sónia Gonçalves, Mavuto Mukaka, Naomi Waithira, Charles J Woodrow, Martin P Grobusch, Michele van Vugt, Rick M Fairhurst, Phaik Yeong Cheah, Thomas J Peto, Lorenz von Seidlein, Mehul Dhorda, Richard J Maude, Markus Winterberg, Nguyen Thanh Thuy-Nhien, Dominic P Kwiatkowski, Mallika Imwong, Podjanee Jittamala, Khin Lin, Tin Maung Hlaing, Kesinee Chotivanich, Rekol Huy, Caterina Fanello, Elizabeth Ashley, Mayfong Mayxay, Paul N Newton, Tran Tinh Hien, Neena Valecha, Frank Smithuis, Sasithon Pukrittayakamee, Abul Faiz, Olivo Miotto, Joel Tarning, Nicholas P J Day, Nicholas J White, Arjen M Dondorp, Nguyen T Thuy-Nhien, Neena Valeche, Nicholas PJ Day, Infectious diseases, AII - Infectious diseases, APH - Aging & Later Life, APH - Global Health, APH - Quality of Care, and Intensive Care Medicine
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medicine.medical_specialty ,Amodiaquine ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,parasitic diseases ,medicine ,Humans ,030212 general & internal medicine ,Artemether ,Artemisinin ,Malaria, Falciparum ,Intention-to-treat analysis ,biology ,business.industry ,Mefloquine ,Plasmodium falciparum ,General Medicine ,Articles ,medicine.disease ,biology.organism_classification ,Artemisinins ,Malaria ,Tolerability ,business ,medicine.drug - Abstract
Summary Background Artemisinin and partner-drug resistance in Plasmodium falciparum are major threats to malaria control and elimination. Triple artemisinin-based combination therapies (TACTs), which combine existing co-formulated ACTs with a second partner drug that is slowly eliminated, might provide effective treatment and delay emergence of antimalarial drug resistance. Methods In this multicentre, open-label, randomised trial, we recruited patients with uncomplicated P falciparum malaria at 18 hospitals and health clinics in eight countries. Eligible patients were aged 2–65 years, with acute, uncomplicated P falciparum malaria alone or mixed with non-falciparum species, and a temperature of 37·5°C or higher, or a history of fever in the past 24 h. Patients were randomly assigned (1:1) to one of two treatments using block randomisation, depending on their location: in Thailand, Cambodia, Vietnam, and Myanmar patients were assigned to either dihydroartemisinin–piperaquine or dihydroartemisinin–piperaquine plus mefloquine; at three sites in Cambodia they were assigned to either artesunate–mefloquine or dihydroartemisinin–piperaquine plus mefloquine; and in Laos, Myanmar, Bangladesh, India, and the Democratic Republic of the Congo they were assigned to either artemether–lumefantrine or artemether–lumefantrine plus amodiaquine. All drugs were administered orally and doses varied by drug combination and site. Patients were followed-up weekly for 42 days. The primary endpoint was efficacy, defined by 42-day PCR-corrected adequate clinical and parasitological response. Primary analysis was by intention to treat. A detailed assessment of safety and tolerability of the study drugs was done in all patients randomly assigned to treatment. This study is registered at ClinicalTrials.gov, NCT02453308, and is complete. Findings Between Aug 7, 2015, and Feb 8, 2018, 1100 patients were given either dihydroartemisinin–piperaquine (183 [17%]), dihydroartemisinin–piperaquine plus mefloquine (269 [24%]), artesunate–mefloquine (73 [7%]), artemether–lumefantrine (289 [26%]), or artemether–lumefantrine plus amodiaquine (286 [26%]). The median age was 23 years (IQR 13 to 34) and 854 (78%) of 1100 patients were male. In Cambodia, Thailand, and Vietnam the 42-day PCR-corrected efficacy after dihydroartemisinin–piperaquine plus mefloquine was 98% (149 of 152; 95% CI 94 to 100) and after dihydroartemisinin–piperaquine was 48% (67 of 141; 95% CI 39 to 56; risk difference 51%, 95% CI 42 to 59; p
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- 2020
40. A Polymorphism in Toll-Interleukin 1 Receptor Domain Containing Adaptor Protein Is Associated with Susceptibility to Meningeal Tuberculosis
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Hawn, Thomas R., Dunstan, Sarah J., Thwaites, Guy E., Simmons, Cameron P., Nguyen Thuong, Thuong, Nguyen Thi Ngoc, Lan, Hoang Thi, Quy, Tran Thi Hong, Chau, Nguyen T., Hieu, Rodrigues, Stephanie, Janer, Marta, Zhao, Lue Ping, Tran Tinh, Hien, Farrar, Jeremy J., and Aderem, Alan
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- 2006
41. Clustering of malaria in households in the Greater Mekong Subregion: operational implications for reactive case detection
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Thomas J. Peto, Mayfong Mayxay, Lorenz von Seidlein, Arjen M. Dondorp, François Nosten, Daniel M. Parker, Tran Tinh Hien, Mallika Imwong, Pimnara Peerawaranun, Koukeo Phommasone, Mavuto Mukaka, Thuy-Nhien Nguyen, Nicholas P. J. Day, Ladda Kajeechiwa, Rupam Tripura, Nicholas J. White, Paul N. Newton, and Intensive Care Medicine
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medicine.medical_specialty ,Asia ,RC955-962 ,Southeastern ,Infectious and parasitic diseases ,RC109-216 ,Asymptomatic ,Microbiology ,Rare Diseases ,Clinical Research ,Arctic medicine. Tropical medicine ,Tropical Medicine ,Epidemiology ,parasitic diseases ,medicine ,Prevalence ,Cluster Analysis ,Mass drug administration ,Asia, Southeastern ,Rapid diagnostic test ,Family Characteristics ,Case detection ,business.industry ,Research ,medicine.disease ,Malaria ,Vector-Borne Diseases ,Infectious Diseases ,Good Health and Well Being ,Parasitology ,Medical Microbiology ,Tropical medicine ,Public Health and Health Services ,medicine.symptom ,business ,Infection ,Case Management ,Demography - Abstract
Background Malaria reactive case detection is the testing and, if positive, treatment of close contacts of index cases. It is included in national malaria control programmes of countries in the Greater Mekong Subregion to accelerate malaria elimination. Yet the value of reactive case detection in the control and elimination of malaria remains controversial because of the low yield, limited evidence for impact, and high demands on resources. Methods Data from the epidemiological assessments of large mass drug administration (MDA) studies in Myanmar, Vietnam, Cambodia and Laos were analysed to explore malaria infection clustering in households. The proportion of malaria positive cases among contacts screened in a hypothetical reactive case detection programme was then determined. The parasite density thresholds for rapid diagnostic test (RDT) detection was assumed to be > 50/µL (50,000/mL), for dried-blood-spot (DBS) based PCR > 5/µL (5000/mL), and for ultrasensitive PCR (uPCR) with a validated limit of detection at 0.0022/µL (22/mL). Results At baseline, before MDA, 1223 Plasmodium infections were detected by uPCR in 693 households. There was clustering of Plasmodium infections. In 637 households with asymptomatic infections 44% (278/637) had more than one member with Plasmodium infections. In the 132 households with symptomatic infections, 65% (86/132) had more than one member with Plasmodium infections. At baseline 4% of households had more than one Plasmodium falciparum infection, but three months after MDA no household had more than one P. falciparum infected member. Reactive case detection using DBS PCR would have detected ten additional cases in six households, and an RDT screen would have detected five additional cases in three households among the 169 households with at least one RDT positive case. This translates to 19 and 9 additional cases identified per 1000 people screened, respectively. Overall, assuming all febrile RDT positive patients would seek treatment and provoke reactive case detection using RDTs, then 1047 of 1052 (99.5%) Plasmodium infections in these communities would have remained undetected. Conclusion Reactive case detection in the Greater Mekong subregion is predicted to have a negligible impact on the malaria burden, but it has substantial costs in terms of human and financial resources.
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- 2021
42. Development of weight and age-based dosing of daily primaquine for radical cure of vivax malaria
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Jordi Landier, Thomas J. Peto, Frank Smithuis, Mavuto Mukaka, Mark Debackere, Walter R. J. Taylor, Lorenz von Seidlein, Arnaud Tarantola, Tran Tinh Hien, Arjen M. Dondorp, Rupam Tripura, Arantxa Roca-Feltrer, Koukeo Phommasone, Pimnara Peerawaranun, Sim Kheng, François Nosten, Nicholas J. White, Philippe Buchy, Joel Tarning, Sinoun Muth, Lek Dysoley, Soy Ty Kheang, Thuy Nguyen, Didier Menard, Ngak Song, Chy Say, Leang Rithea, Mayfong Mayxay, Kak Neeraj, Rick M. Fairhurst, Richard M. Hoglund, Intensive Care Medicine, Graduate School, Radiology and Nuclear Medicine, Mahidol University [Bangkok], University of Oxford, Oxford University Clinical Research Unit [Ho Chi Minh City] (OUCRU), Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), VU University Medical Center [Amsterdam], Shoklo Malaria Research Unit [Mae Sot, Thailand] (SMRU), Mahidol Oxford Tropical Medicine Research Unit (MORU), University of Oxford-Mahidol University [Bangkok]-Wellcome Trust-University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Myanmar Oxford Clinical Research Unit [Yangon, Myanmar], Mahosot Hospital [Vientiane, Laos], Amsterdam Institute for Global Health & Development [Amsterdam, The Netherlands], University of Health Sciences [Vientiane, Laos] (UHS), National Institute of Public Health [Phnom Penh, Cambodge], AQUITY Global Inc [Potomac, MD, USA], University Research Co. [Washington, MD, USA] (URC), National Center for Parasitology, Entomology and Malaria Control [Phnom Penh, Cambodia] (CNM), Malaria Consortium [London, UK] (MCL), MSF Belgium Cambodia Malaria Program [Phnom Penh, Cambodia], National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Keng Kang III Khan Chamkamon [Phnom Penh, Cambodia], GSK Vaccines [Singapore, Singapore], Génétique du paludisme et résistance - Malaria Genetics and Resistance, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), This work was partly supported by a Wellcome Innovator award (WT-iTP-2018/001), but the Wellcome Trust was not involved in any aspect of this study., Malbec, Odile, University of Oxford [Oxford], Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford]-Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Male ,Primaquine ,[SDV]Life Sciences [q-bio] ,RC955-962 ,Plasmodium vivax ,Infectious and parasitic diseases ,RC109-216 ,0302 clinical medicine ,Arctic medicine. Tropical medicine ,030212 general & internal medicine ,Allometric scaling ,Child ,Aged, 80 and over ,biology ,Dosing regimen ,Age Factors ,Middle Aged ,3. Good health ,[SDV] Life Sciences [q-bio] ,Infectious Diseases ,Child, Preschool ,Female ,medicine.drug ,Adult ,Adolescent ,030231 tropical medicine ,Drug Administration Schedule ,03 medical and health sciences ,Antimalarials ,Young Adult ,Animal science ,Pharmacokinetics ,Age-based dosing ,medicine ,Malaria, Vivax ,Humans ,Dosing ,Aged ,business.industry ,Research ,Weight-based dosing ,Body Weight ,Infant ,biology.organism_classification ,Target dose ,Regimen ,Vivax malaria ,Parasitology ,business - 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
43. Genetic surveillance in the Greater Mekong subregion and South Asia to support malaria control and elimination
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Jordi Landier, Abdullah Abu Sayeed, Seila Suon, Kim-Tuyen Nguyen, Kate Rowlands, Frank Smithuis, Chanon Kunasol, Chanaki Amaratunga, Sasithon Pukrittayakamee, Keobouphaphone Chindavongsa, Jacob Almagro Garcia, Richard D. Pearson, Mozam Ali, Xin Hui S Chan, Katie Love, Naomi Park, Pascal Ringwald, Richard J. Maude, Cristina V. Ariani, Mehul Dhorda, Marie A. Onyamboko, Daniel M. Parker, Tin Maung Hlaing, Scott Goodwin, Namfon Kotanan, Thang Ngo Duc, Gilles Delmas, Huy Rekol, Rick M. Fairhurst, Victoria Simpson, Arjen M. Dondorp, Le Thanh Dong, Bouasy Hongvanthong, Tran Tinh Hien, Rapeephan R. Maude, Thomas J. Peto, Shavanthi Rajatileka, Roberto Amato, Thanat Chookajorn, Ben Jeffery, Anna E. Jeffreys, Nicole Zdrojewski, Caterina I. Fanello, Eleanor Drury, Mihir Kekre, Myo Thant, John Sillitoe, Olivo Miotto, Aung Myint Thu, James J Callery, Subrata Baidya, Paul N. Newton, Ranitha Vongpromek, Prativa K Behera, Borimas Hanboonkunupakarn, Rob W. van der Pluijm, Jim Stalker, Anupkumar R. Anvikar, Sonexay Phalivong, Dawn Muddyman, Nguyen Thuy-Nhien, Christina Hubbart, Rithea Leang, Lorenz von Seidlein, Nicholas P. J. Day, Phrutsamon Wongnak, Jonathan Keatley, Hoa Nguyen, Cinzia Malangone, Parthasarathi Satpathi, Abul Faiz, Dysoley Lek, François Nosten, Christopher G Jacob, Rupam Tripura, Sara E. Canavati, Huynh Hong Quang, Kirk A. Rockett, Neena Valecha, Thuy Nguyen, Kimberly J. Johnson, Tran Minh Nhat, Didar Uddin, Caroline O. Buckee, Akhter ul Islam, Podjanee Jittamala, Mayfong Mayxay, Amir Hossain, Viengxay Vanisaveth, Elizabeth A. Ashley, Dominic P. Kwiatkowski, Sanghamitra Satpathi, Aung Pyae Phyo, Amar Tripura, Nguyen Hoang Chau, Sónia Gonçalves, Khin Lin, Cheah Huch, Wellcome Sanger Institute [Hinxton, Royaume-Uni], Oxford University Clinical Research Unit [Ho Chi Minh City] (OUCRU), Mahosot Hospital [Vientiane, Laos], Institute of Research and Education Development [Vientiane, Lao People’s Democratic Republic], University of Health Sciences [Vientiane, Laos] (UHS), University of Oxford [Oxford], Mahidol University [Bangkok], Harvard T.H. Chan School of Public Health, Institute of Malariology, Parasitology, and Entomology [Quy Nhon, Vietnam] (IMPE), Centre of Malariology, Parasitology, and Entomology [Vientiane, Lao People’s Democratic Republic] (CMPE), National Institute of Malariology, Parasitology and Entomology [Hanoi], National Center for Parasitology, Entomology and Malaria Control [Phnom Penh, Cambodia] (CNM), National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Shoklo Malaria Research Unit [Mae Sot, Thailand] (SMRU), Mahidol Oxford Tropical Medicine Research Unit (MORU), University of Oxford [Oxford]-Mahidol University [Bangkok]-Wellcome Trust-University of Oxford [Oxford]-Mahidol University [Bangkok]-Wellcome Trust, Chittagong Medical College Hospital [Chittagong, Bangladesh] (CMCH), World Health Organization [Geneva], Institute of Malariology, Parasitology, and Entomology [Ho Chi Minh City, Vietnam] (IMPE), Vysnova Partners Inc [Hanoi, Vietnam] (VPI), University of Kinshasa (UNIKIN), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of California [Irvine] (UCI), University of California, Royal Society of Thailand [Bangkok, Thailand], Myanmar Oxford Clinical Research Unit [Yangon, Myanmar], The Department of Medical Research (Upper Myanmar), Defence Services Medical Research Centre [Naypyitaw, Myanmar] (DSMRC), Midnapore Medical College [Midnapur, India] (MMC), ispat general hospital [Rourkela, India] (IGH), Agartala Medical College [Agartala, India] (AMC), National Institute of Malaria Research [New Dehli, Inde] (NIMR), Indian Council of Medical Research [New Dehli] (ICMR), Ramu Upazila Health Complex [Cox’s Bazar, Bangladesh] (RUHC), The Wellcome Trust Sanger Institute [Cambridge], WorldWide Antimalarial Resistance Network [Bangkok] (WWARN), WorldWide Antimalarial Resistance Network (WWARN), Université de Washington Seattle-Université de Washington Seattle, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford, University of Oxford-Mahidol University [Bangkok]-Wellcome Trust-University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, University of California [Irvine] (UC Irvine), University of California (UC), University of Washington [Seattle]-University of Washington [Seattle], and Malbec, Odile
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Plasmodium ,History ,[SDV]Life Sciences [q-bio] ,Drug Resistance ,global health ,Drug resistance ,Barcode ,law.invention ,law ,Genotype ,Biology (General) ,Aetiology ,Microbiology and Infectious Disease ,0303 health sciences ,Bangladesh ,General Neuroscience ,General Medicine ,asia ,3. Good health ,[SDV] Life Sciences [q-bio] ,Geography ,Infectious Diseases ,Democratic Republic of the Congo ,Medicine ,epidemiology ,Genetic Engineering ,Malaria control ,Infection ,Research Article ,medicine.medical_specialty ,South asia ,Asia ,QH301-705.5 ,Science ,infectious disease ,Plasmodium falciparum ,malaria ,Library science ,Southeastern ,India ,General Biochemistry, Genetics and Molecular Biology ,Antimalarials ,03 medical and health sciences ,Rare Diseases ,Simple sample ,Clinical Research ,Environmental health ,medicine ,Genetics ,Humans ,Animals ,Disease Eradication ,030304 developmental biology ,drug resistance ,General Immunology and Microbiology ,030306 microbiology ,Public health ,microbiology ,Genetic data ,Genetic Therapy ,medicine.disease ,genetic surveillance ,Compendium ,Resistance monitoring ,Data sharing ,Vector-Borne Diseases ,Epidemiology and Global Health ,Good Health and Well Being ,Communicable Disease Control ,Antimicrobial Resistance ,Biochemistry and Cell Biology ,Malaria ,2.6 Resources and infrastructure (aetiology) - Abstract
Author(s): 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, Francois; 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 | 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
44. LTA4H genotype is associated with susceptibility to bacterial meningitis but is not a critical determinant of outcome.
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Sarah J Dunstan, Trinh Thi Bich Tram, Guy E Thwaites, Tran Thi Hong Chau, Nguyen Hoan Phu, Tran Tinh Hien, Jeremy J Farrar, Marcel Wolbers, and Nguyen Thi Hoang Mai
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Medicine ,Science - Abstract
Adjunctive dexamethasone saves lives in the treatment of tuberculous meningitis but this response is influenced by the patient's LTA4H genotype. Despite less certain benefit, adjunctive dexamethasone is also frequently used in the treatment of pyogenic bacterial meningitis, but the influence of LTA4H genotype on outcomes has not been previously investigated. We genotyped the LTA4H promoter region SNP (rs17525495) in 390 bacterial meningitis patients and 751 population controls. rs17525495 was associated with susceptibility to bacteriologically confirmed bacterial meningitis (P = 0.01, OR 1.27 95% confidence interval [CI] 1.05-1.54) but did not influence clinical presentation, disease severity or survival following dexamethasone treatment.
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- 2015
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45. An open dataset of
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Ambroise, Ahouidi, Mozam, Ali, Jacob, Almagro-Garcia, Alfred, Amambua-Ngwa, Chanaki, Amaratunga, Roberto, Amato, Lucas, Amenga-Etego, Ben, Andagalu, Tim J C, Anderson, Voahangy, Andrianaranjaka, Tobias, Apinjoh, Cristina, Ariani, Elizabeth A, Ashley, Sarah, Auburn, Gordon A, Awandare, Hampate, Ba, Vito, Baraka, Alyssa E, Barry, Philip, Bejon, Gwladys I, Bertin, Maciej F, Boni, Steffen, Borrmann, Teun, Bousema, Oralee, Branch, Peter C, Bull, George B J, Busby, Thanat, Chookajorn, Kesinee, Chotivanich, Antoine, Claessens, David, Conway, Alister, Craig, Umberto, D'Alessandro, Souleymane, Dama, Nicholas Pj, Day, Brigitte, Denis, Mahamadou, Diakite, Abdoulaye, Djimdé, Christiane, Dolecek, Arjen M, Dondorp, Chris, Drakeley, Eleanor, Drury, Patrick, Duffy, Diego F, Echeverry, Thomas G, Egwang, Berhanu, Erko, Rick M, Fairhurst, Abdul, Faiz, Caterina A, Fanello, Mark M, Fukuda, Dionicia, Gamboa, Anita, Ghansah, Lemu, Golassa, Sonia, Goncalves, William L, Hamilton, G L Abby, Harrison, Lee, Hart, Christa, Henrichs, Tran Tinh, Hien, Catherine A, Hill, Abraham, Hodgson, Christina, Hubbart, Mallika, Imwong, Deus S, Ishengoma, Scott A, Jackson, Chris G, Jacob, Ben, Jeffery, Anna E, Jeffreys, Kimberly J, Johnson, Dushyanth, Jyothi, Claire, Kamaliddin, Edwin, Kamau, Mihir, Kekre, Krzysztof, Kluczynski, Theerarat, Kochakarn, Abibatou, Konaté, Dominic P, Kwiatkowski, Myat Phone, Kyaw, Pharath, Lim, Chanthap, Lon, Kovana M, Loua, Oumou, Maïga-Ascofaré, Cinzia, Malangone, Magnus, Manske, Jutta, Marfurt, Kevin, Marsh, Mayfong, Mayxay, Alistair, Miles, Olivo, Miotto, Victor, Mobegi, Olugbenga A, Mokuolu, Jacqui, Montgomery, Ivo, Mueller, Paul N, Newton, Thuy, Nguyen, Thuy-Nhien, Nguyen, Harald, Noedl, Francois, Nosten, Rintis, Noviyanti, Alexis, Nzila, Lynette I, Ochola-Oyier, Harold, Ocholla, Abraham, Oduro, Irene, Omedo, Marie A, Onyamboko, Jean-Bosco, Ouedraogo, Kolapo, Oyebola, Richard D, Pearson, Norbert, Peshu, Aung Pyae, Phyo, Chris V, Plowe, Ric N, Price, Sasithon, Pukrittayakamee, Milijaona, Randrianarivelojosia, Julian C, Rayner, Pascal, Ringwald, Kirk A, Rockett, Katherine, Rowlands, Lastenia, Ruiz, David, Saunders, Alex, Shayo, Peter, Siba, Victoria J, Simpson, Jim, Stalker, Xin-Zhuan, Su, Colin, Sutherland, Shannon, Takala-Harrison, Livingstone, Tavul, Vandana, Thathy, Antoinette, Tshefu, Federica, Verra, Joseph, Vinetz, Thomas E, Wellems, Jason, Wendler, Nicholas J, White, Ian, Wright, William, Yavo, and Htut, Ye
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data resource ,drug resistance ,plasmodium falciparum ,parasitic diseases ,evolution ,malaria ,genomics ,rapid diagnostic test failure ,population genetics ,Articles ,genomic epidemiology ,Research Article - Abstract
MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.
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- 2021
46. Author response: Genetic surveillance in the Greater Mekong subregion and South Asia to support malaria control and elimination
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Jordi Landier, Frank Smithuis, Huy Rekol, Amar Tripura, Rapeephan R. Maude, Keobouphaphone Chindavongsa, Thomas J. Peto, Khin Lin, Dominic P. Kwiatkowski, Cristina V. Ariani, Naomi Park, Cheah Huch, Jacob Almagro Garcia, Sanghamitra Satpathi, Kimberly J. Johnson, Daniel M. Parker, Dawn Muddyman, Rithea Leang, Arjen M. Dondorp, Anna E. Jeffreys, Tin Maung Hlaing, Richard D. Pearson, Hoa Nguyen, Le Thanh Dong, Caroline O. Buckee, Scott Goodwin, Seila Suon, Ben Jeffery, Mihir Kekre, Caterina I. Fanello, Rupam Tripura, Kate Rowlands, Kirk A. Rockett, Rob W. van der Pluijm, Rick M. Fairhurst, Sonexay Phalivong, Namfon Kotanan, Sasithon Pukrittayakamee, Abdullah Abu Sayeed, Thang Ngo Duc, Nicholas P. J. Day, Shavanthi Rajatileka, Aung Myint Thu, James J Callery, Huynh Hong Quang, Eleanor Drury, Victoria Simpson, Myo Thant, Sara E. Canavati, Abul Faiz, Akhter ul Islam, Dysoley Lek, Christopher G Jacob, Jim Stalker, Anupkumar R. Anvikar, Chanon Kunasol, Lorenz von Seidlein, Podjanee Jittamala, Mayfong Mayxay, Elizabeth A. Ashley, Subrata Baidya, Paul N. Newton, Prativa K Behera, Parthasarathi Satpathi, François Nosten, Tran Minh Nhat, Borimas Hanboonkunupakarn, Pascal Ringwald, Neena Valecha, Thuy Nguyen, Didar Uddin, Christina Hubbart, Amir Hossain, Cinzia Malangone, Bouasy Hongvanthong, Aung Pyae Phyo, Tran Tinh Hien, Nicole Zdrojewski, Kim-Tuyen Nguyen, Ranitha Vongpromek, Chanaki Amaratunga, Nguyen Hoang Chau, Katie Love, Marie A. Onyamboko, Richard J. Maude, Xin Hui S Chan, Nguyen Thuy-Nhien, Phrutsamon Wongnak, Sónia Gonçalves, Jonathan Keatley, Mozam Ali, Mehul Dhorda, Roberto Amato, John Sillitoe, Olivo Miotto, Gilles Delmas, Viengxay Vanisaveth, and Thanat Chookajorn
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South asia ,Geography ,Socioeconomics ,Malaria control - Published
- 2021
47. The mechanism of artemisinin resistance of Plasmodium falciparum malaria parasites originates in their initial transcriptional response
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Paul N. Newton, Hagai Ginsburg, Aung Pyae Phyo, Arjen M. Dondorp, Frank Smithuis, Podjanee Jittamala, Mayfong Mayxay, Nguyen Hoang Chau, Rob W. van der Pluijm, Nhien Nguyen Thanh Thuy Thuy, Khin Lin, Elizabeth A. Ashley, Nicholas J. White, François Nosten, Tran Tinh Hien, Mehul Dhorda, Zbynek Bozdech, Lorenz von Seidlein, Nicholas P. J. Day, Michal Kucharski, Abul Faiz, Dysoley Lek, Jaishree Tripathi, Sourav Nayak, Chanak Amaratunga, Rupam Tripura, Lei Zhu, Olivo Miotto, Thomas J. Peto, Mallika Imwong, and Sasithon Pukrittayakamee
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Genetics ,biology ,Mechanism (biology) ,Artemisinin resistance ,Plasmodium falciparum ,medicine.disease ,biology.organism_classification ,Redox metabolism ,Transcriptome ,parasitic diseases ,medicine ,Transcriptional response ,Artemisinin ,Malaria ,medicine.drug - Abstract
The emergence and spread of artemisinin resistant Plasmodium falciparum, first in the Greater Mekong Subregion (GMS), and now in East Africa, is a major threat to global malaria eliminations ambitions. To investigate the artemisinin resistance mechanism, transcriptome analysis was conducted of 577 P. falciparum isolates collected in the GMS between 2016-2018. A specific artemisinin resistance-associated transcriptional profile was identified that involves a broad but discrete set of biological functions related to proteotoxic stress, host cytoplasm remodeling and REDOX metabolism. The artemisinin resistance-associated transcriptional profile evolved from initial transcriptional responses of susceptible parasites to artemisinin. The genetic basis for this adapted response is likely to be complex. One sentence summary The transcriptional profile that characterize artemisinin resistant infections with malaria parasites Plasmodium falciparum originates in the initial transcriptional response to the drug.
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- 2021
48. The mechanism of artemisinin resistance of Plasmodium falciparum malaria parasites originates in their initial transcriptional response
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Lei Zhu, Rob W. van der Pluijm, Michal Kucharski, Sourav Nayak, Jaishree Tripathi, François Nosten, Abul Faiz, Chanaki Amaratunga, Dysoley Lek, Elizabeth A Ashley, Frank Smithuis, Aung Pyae Phyo, Khin Lin, Mallika Imwong, Mayfong Mayxay, Mehul Dhorda, Nguyen Hoang Chau, Nhien Nguyen Thanh Thuy, Paul N Newton, Podjanee Jittamala, Rupam Tripura, Sasithon Pukrittayakamee, Thomas J Peto, Olivo Miotto, Lorenz von Seidlein, Tran Tinh Hien, Hagai Ginsburg, Nicholas PJ Day, Nicholas J. White, Arjen M Dondorp, and Zbynek Bozdech
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parasitic diseases - Abstract
The emergence and spread of artemisinin resistant Plasmodium falciparum, first in the Greater Mekong Subregion (GMS), and now in East Africa, is a major threat to global malaria eliminations ambitions. To investigate the artemisinin resistance mechanism, transcriptome analysis was conducted of 577 P. falciparum isolates collected in the GMS between 2016-2018. A specific artemisinin resistance-associated transcriptional profile was identified that involves a broad but discrete set of biological functions related to proteotoxic stress, host cytoplasm remodeling and REDOX metabolism. The artemisinin resistance-associated transcriptional profile evolved from initial transcriptional responses of susceptible parasites to artemisinin. The genetic basis for this adapted response is likely to be complex.One sentence summaryThe transcriptional profile that characterize artemisinin resistant infections with malaria parasites Plasmodium falciparum originates in the initial transcriptional response to the drug.
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- 2021
49. Within-host evolutionary dynamics of seasonal and pandemic human influenza A viruses in young children
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Han, Alvin X, primary, Felix Garza, Zandra C, additional, Welkers, Matthijs RA, additional, Vigeveno, René M, additional, Tran, Nhu Duong, additional, Le, Thi Quynh Mai, additional, Pham Quang, Thai, additional, Dang, Dinh Thoang, additional, Tran, Thi Ngoc Anh, additional, Ha, Manh Tuan, additional, Nguyen, Thanh Hung, additional, Le, Quoc Thinh, additional, Le, Thanh Hai, additional, Hoang, Thi Bich Ngoc, additional, Chokephaibulkit, Kulkanya, additional, Puthavathana, Pilaipan, additional, Nguyen, Van Vinh Chau, additional, Nghiem, My Ngoc, additional, Nguyen, Van Kinh, additional, Dao, Tuyet Trinh, additional, Tran, Tinh Hien, additional, Wertheim, Heiman FL, additional, Horby, Peter W, additional, Fox, Annette, additional, van Doorn, H Rogier, additional, Eggink, Dirk, additional, de Jong, Menno D, additional, and Russell, Colin A, additional
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- 2021
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50. Author response: Within-host evolutionary dynamics of seasonal and pandemic human influenza A viruses in young children
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Han, Alvin X, primary, Felix Garza, Zandra C, additional, Welkers, Matthijs RA, additional, Vigeveno, René M, additional, Tran, Nhu Duong, additional, Le, Thi Quynh Mai, additional, Pham Quang, Thai, additional, Dang, Dinh Thoang, additional, Tran, Thi Ngoc Anh, additional, Ha, Manh Tuan, additional, Nguyen, Thanh Hung, additional, Le, Quoc Thinh, additional, Le, Thanh Hai, additional, Hoang, Thi Bich Ngoc, additional, Chokephaibulkit, Kulkanya, additional, Puthavathana, Pilaipan, additional, Nguyen, Van Vinh Chau, additional, Nghiem, My Ngoc, additional, Nguyen, Van Kinh, additional, Dao, Tuyet Trinh, additional, Tran, Tinh Hien, additional, Wertheim, Heiman FL, additional, Horby, Peter W, additional, Fox, Annette, additional, van Doorn, H Rogier, additional, Eggink, Dirk, additional, de Jong, Menno D, additional, and Russell, Colin A, additional
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- 2021
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