77 research outputs found
Metadata, the undiscovered treasure box for book recommender systems for children: What traits can be inferred from book’s descriptive and structural metadata which could support the designers of books recommender systems for children?
No full textThis study examines traits that may be derived from book metadata and identifies statistically signifi- cant patterns and trends in order to assist recom- mender system designers for children’s books in selecting the most important traits to take into ac- count. This research focuses on descriptive such as publish year and structural metadata such as the chapters’ count. We rely on data from two different data sets, Goodreads and Wikisource.The findings of this study, such as the fact that there is a relationship between the number of pages and the reader’s age, may have an impact on the design of recommender systems for children’s books.This is all with the respect to the fact that children are a vulnerable audience, making it challenging to not infringe on their privacy while gathering infor- mation that can be used in statistical experiments in many fields such as education and health.CSE3000 Research ProjectComputer Science and Engineerin
Rolling out the radical cure for vivax malaria in Asia: a qualitative study among policy makers and stakeholders
No full textIntroduction: Plasmodium vivax is the predominant cause of malaria in the Greater Mekong Subregion. To ensure safe treatment with primaquine, point-of-care glucose-6-phosphate dehydrogenase (G6PD) testing was rolled out in Cambodia at the health facility level, although most malaria patients are diagnosed in the community. The current study aims to explore the acceptability and feasibility of implementing community-level G6PD testing in Cambodia. Methods: Semistructured interviews and focus group discussions (FGD) were conducted. Across eight study sites in three provinces, 142 respondents, including policymakers, programme officers, healthcare providers and patients, participated in 67 interviews and 19 FGDs in 2022 and 2023. Data were analysed thematically using an adapted framework derived from Bowen et al’s feasibility framework and Sekhon et al’s acceptability framework. Results: All stakeholders attributed value to the intervention. Acknowledging an intervention’s different values can help discern policy implications for an intervention’s successful implementation. Building and maintaining confidence in the device, end users, infrastructure and health systems were found to be key elements of acceptability. In general, health centre workers and village malaria workers (VMWs) had confidence that VMWs could conduct the test and administer treatment given appropriate initial training, monthly refresher training and the test’s repeated use. More is required to build policymakers’ confidence, while some implementation challenges, including the test’s regulatory approval, stability above 30°C and cost, need to be overcome. Conclusion: Implementation of G6PD testing at the community level in Cambodia is an acceptable and potentially feasible option but requires addressing implementation challenges and building and maintaining confidence among stakeholder
Dihydroartemisinin-piperaquine versus chloroquine to treat vivax malaria in Afghanistan: an open randomized, non-inferiority, trial.
No full textBACKGROUND: Afghanistan's national guidelines recommend chloroquine for the treatment of Plasmodium vivax infection, the parasite responsible for the majority of its malaria burden. Chloroquine resistance in P. vivax is emerging in Asia. Therapeutic responses across Afghanistan have not been evaluated in detail.
METHODS: Between July 2007 and February 2009, an open-label, randomized controlled trial of chloroquine and dihydroartemisinin-piperaquine in patients aged three months and over with slide-confirmed P. vivax mono-infections was conducted. Consistent with current national guidelines, primaquine was not administered. Subjects were followed up daily during the acute phase of illness (days 0-3) and weekly until day 56. The primary endpoint was the overall cumulative parasitological failure rate at day 56 after the start of treatment, with the hypothesis being that dihydroartemisinin-piperaquine was non-inferior compared to chloroquine (Delta = 5% difference in proportion of failures).
RESULTS: Of 2,182 individuals with positive blood films for P. vivax, 536 were enrolled in the trial. The day 28 cure rate was 100% in both treatment groups. Parasite clearance was more rapid with dihydroartemisinin-piperaquine than chloroquine. At day 56, there were more recurrent infections in the chloroquine arm (8.9%, 95% CI 6.0-13.1%) than the dihydroartemisinin-piperaquine arm (2.8%, 95% CI 1.4-5.8%), a difference in cumulative recurrence rate of 6.1% (2-sided 90%CI +2.6 to +9.7%). The log-rank test comparing the survival curves confirmed the superiority of dihydroartemisinin-piperaquine over chloroquine (p = 0.003). Multivariate analysis showed that a lower initial haemoglobin concentration was also independently associated with recurrence. Both regimens were well tolerated and no serious adverse events were reported.
CONCLUSIONS: Chloroquine remains an efficacious treatment for the treatment of vivax malaria in Afghanistan. In a setting where radical therapy cannot be administered, dihydroartemisinin-piperaquine provides additional benefit in terms of post-treatment prophylaxis, reducing the incidence of recurrence from 4-8 weeks after treatment
Polymorphisms in Plasmodium vivax antifolate resistance markers in Afghanistan between 2007 and 2017
No full textBACKGROUND:Plasmodium vivax is the predominant Plasmodium species in Afghanistan. National guidelines recommend the combination of chloroquine and primaquine (CQ-PQ) for radical treatment of P. vivax malaria. Artesunate in combination with the antifolates sulfadoxine-pyrimethamine (SP) has been first-line treatment for uncomplicated falciparum malaria until 2016. Although SP has been the recommended treatment for falciparum and not vivax malaria, exposure of the P. vivax parasite population to SP might still have been quite extensive because of community based management of malaria. The change in the P. vivax antifolate resistance markers between 2007 and 2017 were investigated. METHODS:Dried blood spots were collected (n = 185) from confirmed P. vivax patients in five malaria-endemic areas of Afghanistan bordering Tajikistan, Turkmenistan and Pakistan, including Takhar, Faryab, Laghman, Nangarhar, and Kunar, in 2007, 2010 and 2017. Semi-nested PCR, RFLP and nucleotide sequencing were used to assess the pyrimethamine resistant related mutations in P. vivax dihydrofolate reductase (pvdhfr I13L, P33L, N50I, F57L, S58R, T61I, S93H, S117N, I173L) and the sulfonamide resistance related mutations in P. vivax dihydropteroate synthase (pvdhps A383G, A553G). RESULTS:In the 185 samples genotyped for pvdhfr and pvdhps mutations, 11 distinct haplotypes were observed, which evolved over time. In 2007, wild type pvdhfr and pvdhps were the most frequent haplotype in all study sites (81%, 80/99). However, in 2017, the frequency of the wild-type was reduced to 36%, (21/58; p value ≤ 0.001), with an increase in frequency of the double mutant pvdhfr and pvdhps haplotype S58RS117N (21%, 12/58), and the single pvdhfr mutant haplotype S117N (14%, 8/58). Triple and quadruple mutations were not found. In addition, pvdhfr mutations at position N50I (7%, 13/185) and the novel mutation S93H (6%, 11/185) were observed. Based on in silico protein modelling and molecular docking, the pvdhfr N50I mutation is expected to affect only moderately pyrimethamine binding, whereas the S93H mutation does not. CONCLUSIONS:In the course of ten years, there has been a strong increase in the frequency pyrimethamine resistance related mutations in pvdhfr in the P. vivax population in Afghanistan, although triple and quadruple mutations conferring high grade resistance were not observed. This suggests relatively low drug pressure from SP on the P. vivax parasite population in the study areas. The impact of two newly identified mutations in the pvdhfr gene on pyrimethamine resistance needs further investigation
Protective effect of Mediterranean-type glucose-6-phosphate dehydrogenase deficiency against Plasmodium vivax malaria
No full textX-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy. The severe Mediterranean variant (G6PD Med) found across Europe and Asia is thought to confer protection against malaria, but its effect is unclear. We fitted a Bayesian statistical model to observed G6PD Med allele frequencies in 999 Pashtun patients presenting with acute Plasmodium vivax malaria and 1408 population controls. G6PD Med was associated with reductions in symptomatic P. vivax malaria incidence of 76% (95% credible interval [CI], 58–88) in hemizygous males and homozygous females combined and 55% (95% CI, 38–68) in heterozygous females. Unless there is very large population stratification within the Pashtun (confounding these results), the G6PD Med genotype confers a very large and gene-dose proportional protective effect against acute vivax malaria. The proportion of patients with vivax malaria at risk of haemolysis following 8-aminoquinoline radical cure is substantially overestimated by studies measuring G6PD deficiency prevalence in healthy subjects
A Worldwide Map of Plasmodium falciparum K13-Propeller Polymorphisms
No full textThe authors’ full names and academic degrees are as follows: Didier Ménard, Ph.D., Nimol Khim, Ph.D., Johann Beghain, M.Sc.,
Ayola A. Adegnika, M.D., Ph.D., Mohammad Shafiul-Alam, Ph.D., Olukemi Amodu, Ph.D., Ghulam Rahim-Awab, Ph.D., Céline Barnadas,
Ph.D., Antoine Berry, M.D., Ph.D., Yap Boum, Ph.D., Maria D. Bustos, M.D., Ph.D., Jun Cao, Ph.D., Jun-Hu Chen, Ph.D., Louis
Collet, M.D., Liwang Cui, Ph.D., Garib-Das Thakur, M.D., Alioune Dieye, Pharm.D., Ph.D., Djibrine Djallé, M.Sc., Monique A. Dorkenoo,
M.D., Carole E. Eboumbou-Moukoko, Ph.D., Fe-Esperanza-Caridad J. Espino, M.D., Ph.D., Thierry Fandeur, Ph.D., Maria-Fatima
Ferreira-da-Cruz, Ph.D., Abebe A. Fola, M.Sc., Hans-Peter Fuehrer, Ph.D., Abdillahi M. Hassan, B.Sc., Socrates Herrera, M.D., Bouasy
Hongvanthong, M.D., Sandrine Houzé, M.D., Ph.D., Maman L. Ibrahim, M.V.D., Ph.D., Mohammad Jahirul-Karim, M.B., B.S., Lubin
Jiang, Ph.D., Shigeyuki Kano, M.D., Ph.D., Wasif Ali-Khan, M.B., B.S., Maniphone Khanthavong, M.D., Peter G. Kremsner, M.D.,
Marcus Lacerda, M.D., Ph.D., Rithea Leang, M.D., Mindy Leelawong, Ph.D., Mei Li, Ph.D., Khin Lin, M.D., Jean-Baptiste Mazarati,
Ph.D., Sandie Ménard, M.Sc., Isabelle Morlais, Ph.D., Hypolite Muhindo-Mavoko, M.D., Lise Musset, Pharm.D., Ph.D., Kesara
Na-Bangchang, Ph.D., Michael Nambozi, M.P.H., Karamoko Niaré, Pharm.D., Harald Noedl, M.D., Ph.D., Jean-Bosco Ouédraogo,
M.D., Ph.D., Dylan R. Pillai, M.D., Ph.D., Bruno Pradines, Pharm.D., Ph.D., Bui Quang-Phuc, M.D., Michael Ramharter, M.D.,
D.T.M.H., Milijaona Randrianarivelojosia, Ph.D., Jetsumon Sattabongkot, Ph.D., Abdiqani Sheikh-Omar, M.D., Kigbafori D. Silué, Ph.D., Sodiomon B. Sirima, M.D., Ph.D., Colin Sutherland, Ph.D., M.P.H., Din Syafruddin, M.D., Ph.D., Rachida Tahar, Ph.D., Lin-Hua
Tang, M.D., Ph.D., Offianan A. Touré, Ph.D., Patrick Tshibangu-wa-Tshibangu, M.D., Inès Vigan-Womas, Ph.D., Marian Warsame, M.D.,
Ph.D., Lyndes Wini, M.B., B.S., Sedigheh Zakeri, Ph.D., Saorin Kim, B.S., Rotha Eam, B.S., Laura Berne, M.Sc., Chanra Khean, B.S., Sophy
Chy, B.S., Malen Ken, B.S., Kaknika Loch, B.S., Lydie Canier, M.Sc., Valentine Duru, M.Sc., Eric Legrand, Ph.D., Jean-Christophe Barale,
Ph.D., Barbara Stokes, B.Sc., Judith Straimer, Ph.D., Benoit Witkowski, Ph.D., David A. Fidock, Ph.D., Christophe Rogier, M.D., Ph.D.,
Pascal Ringwald, M.D., Frederic Ariey, M.D., Ph.D., and Odile Mercereau-Puijalon, Ph.D.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ. Brasil.BACKGROUND
Recent gains in reducing the global burden of malaria are threatened by the emergence of
Plasmodium falciparum resistance to artemisinins. The discovery that mutations in portions
of a P. falciparum gene encoding kelch (K13)–propeller domains are the major determinant
of resistance has provided opportunities for monitoring such resistance on a global scale.
METHODS
We analyzed the K13-propeller sequence polymorphism in 14,037 samples collected in
59 countries in which malaria is endemic. Most of the samples (84.5%) were obtained
from patients who were treated at sentinel sites used for nationwide surveillance of
antimalarial resistance. We evaluated the emergence and dissemination of mutations
by haplotyping neighboring loci.
RESULTS
We identified 108 nonsynonymous K13 mutations, which showed marked geographic
disparity in their frequency and distribution. In Asia, 36.5% of the K13 mutations were
distributed within two areas — one in Cambodia, Vietnam, and Laos and the other in
western Thailand, Myanmar, and China — with no overlap. In Africa, we observed a
broad array of rare nonsynonymous mutations that were not associated with delayed
parasite clearance. The gene-edited Dd2 transgenic line with the A578S mutation, which
expresses the most frequently observed African allele, was found to be susceptible to
artemisinin in vitro on a ring-stage survival assay.
CONCLUSIONS
No evidence of artemisinin resistance was found outside Southeast Asia and China,
where resistance-associated K13 mutations were confined. The common African A578S
allele was not associated with clinical or in vitro resistance to artemisinin, and many
African mutations appear to be neutral. (Funded by Institut Pasteur Paris and others
Strong protective effect of Mediterranean type glucose-6-phosphate dehydrogenase deficiency against vivax malaria
No full textLancet Infect Dis
No full textBackgroundPrimaquine radical cure is used to treat dormant liver-stage parasites and prevent relapsing Plasmodium vivax malaria but is limited by concerns of haemolysis. We undertook a systematic review and individual patient data meta-analysis to investigate the haematological safety of different primaquine regimens for P vivax radical cure.MethodsFor this systematic review and individual patient data meta-analysis, we searched MEDLINE, Web of Science, Embase, and Cochrane Central for prospective clinical studies of uncomplicated P vivax from endemic countries published between Jan 1, 2000, and June 8, 2023. We included studies if they had active follow-up of at least 28 days, if they included a treatment group with daily primaquine given over multiple days where primaquine was commenced within 3 days of schizontocidal treatment and was given alone or coadministered with chloroquine or one of four artemisinin-based combination therapies (ie, artemether\u2013lumefantrine, artesunate\u2013mefloquine, artesunate\u2013amodiaquine, or dihydroartemisinin\u2013piperaquine), and if they recorded haemoglobin or haematocrit concentrations on day 0. We excluded studies if they were on prevention, prophylaxis, or patients with severe malaria, or if data were extracted retrospectively from medical records outside of a planned trial. For the meta-analysis, we contacted the investigators of eligible trials to request individual patient data and we then pooled data that were made available by Aug 23, 2021. The main outcome was haemoglobin reduction of more than 25% to a concentration of less than 7 g/dL by day 14. Haemoglobin concentration changes between day 0 and days 2\u20133 and between day 0 and days 5\u20137 were assessed by mixed-effects linear regression for patients with glucose-6-phosphate dehydrogenase (G6PD) activity of (1) 30% or higher and (2) between 30% and less than 70%. The study was registered with PROSPERO, CRD42019154470 and CRD42022303680.FindingsOf 226 identified studies, 18 studies with patient-level data from 5462 patients from 15 countries were included in the analysis. A haemoglobin reduction of more than 25% to a concentration of less than 7 g/dL occurred in one (0\ub71%) of 1208 patients treated without primaquine, none of 893 patients treated with a low daily dose of primaquine (<0\ub7375 mg/kg per day), five (0\ub73%) of 1464 patients treated with an intermediate daily dose (0\ub7375 mg/kg per day to <0\ub775 mg/kg per day), and six (0\ub75%) of 1269 patients treated with a high daily dose ( 650\ub775 mg/kg per day). The covariate-adjusted mean estimated haemoglobin changes at days 2\u20133 were 120\ub76 g/dL (95% CI 120\ub77 to 120\ub75), 120\ub77 g/dL (\u20130\ub78 to 120\ub75), 120\ub76 g/dL (\u20130\ub77 to 120\ub74), and 120\ub75 g/dL (\u20130\ub77 to 120\ub74), respectively. In 51 patients with G6PD activity between 30% and less than 70%, the adjusted mean haemoglobin concentration on days 2\u20133 decreased as G6PD activity decreased; two patients in this group who were treated with a high daily dose of primaquine had a reduction of more than 25% to a concentration of less than 7 g/dL. 17 of 18 included studies had a low or unclear risk of bias.InterpretationTreatment of patients with G6PD activity of 30% or higher with 0\ub725\u20130\ub75 mg/kg per day primaquine regimens and patients with G6PD activity of 70% or higher with 0\ub725\u20131 mg/kg per day regimens were associated with similar risks of haemolysis to those in patients treated without primaquine, supporting the safe use of primaquine radical cure at these doses.FundingAustralian National Health and Medical Research Council, Bill & Melinda Gates Foundation, and Medicines for Malaria Venture.WT_/Wellcome TrustUnited Kingdom/200909/WT_/Wellcome TrustUnited Kingdom/CC999999/ImCDC/Intramural CDC HHSUnited States
A population survey of the glucose-6-phosphate dehydrogenase (G6PD) 563C>T (Mediterranean) mutation in Afghanistan
No full textGlucose-6-phosphate dehydrogenase (G6PD) deficiency is a common inherited enzyme defect and an important problem in areas with Plasmodium vivax infection because of the risk of haemolysis following administration of primaquine to treat the liver forms of the parasite. We undertook a genotypic survey of 713 male individuals across nine provinces of Afghanistan in which malaria is found, four in the north and five in the east. RFLP typing at nucleotide position 563 detected 40 individuals with the Mediterranean mutation 563C>T, an overall prevalence of 5.6%. This varied according to self-reported ethnicity, with prevalence in the Pashtun/Pashai group of 33/369 (8.9%) compared to 7/344 individuals in the rest of the population (2.0%; pT in exon 11, and C93T in intron XI) in a subset of 82 individuals wild-type at C563 revealed a mixture of 3 haplotypes in the background population and was consistent with data from the 1000 Genomes Project and published studies. By comparison individuals with G6PD deficiency showed a highly skewed haplotype distribution, with 95% showing the CT haplotype, a finding consistent with relatively recent appearance and positive selection of the Mediterranean variant in Afghanistan. Overall, the data confirm that the Mediterranean variant of G6PD is common in many ethnic groups in Afghanistan, indicating that screening for G6PD deficiency is required in all individuals before radical treatment of P. vivax with primaquine
Chloroquine–Primaquine versus Chloroquine Alone to Treat Vivax Malaria in Afghanistan: An Open Randomized Superiority Trial
No full textBackground
Afghanistan’s national guidelines recommend primaquine for radical treatment of P. vivax malaria but this is rarely implemented because of concerns over potential hemolysis in patients who have G6PD deficiency.
Methods
Between August 2009 and February 2014, we conducted an open-label, randomized controlled trial of chloroquine (CQ) alone versus chloroquine plus primaquine (0.25mg base/kg/day for 14 days)(CQ+PQ) in patients aged > 6 months with microscopy confirmed P. vivax infection. In the CQ+PQ group G6PD deficiency was excluded by fluorescent spot testing. The primary outcome was P. vivax recurrence assessed by survival analysis.
Results
Of 593 patients enrolled, 570 attended at or after 14 days of follow-up. P. vivax recurrences occurred in 37 (13.1%) of 282 patients in the CQ+PQ arm versus 86 (29.9%) of 288 in the CQ arm . Cox Proportional Hazard Ratio 0.37, 95% CI 0.25 – 0.54) (ITT analysis). Protection against recurrence was greater in the first six months of follow-up (HR 0.082; 95% CI 0.029-0.23) than later (HR 0.65, 95% CI 0.41-1.03). Five of seven patients requiring hospital admission were considered possible cases of PQ-related hemolysis, and PQ was stopped in a further six; however in none of these cases did hemoglobin fall by >2g/dl or to below 7 g/dl.
Conclusions
Primaquine 0.25mg/kg/day for 14 days prevents relapse of P. vivax in Afghanistan. Patient visits during the first week may improve adherence. Implementation will require deployment of point of care phenotypic tests for G6PD deficiency.</p
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