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INTRODUCTION: Screening for G6PD deficiency can inform disease management including malaria. Treatment with the antimalarial drugs primaquine and tafenoquine can be guided by point-of-care testing for G6PD deficiency. METHODS AND FINDINGS: Data from similar clinical studies evaluating the performance of the STANDARD G6PD Test (SD Biosensor, South Korea) conducted in Bangladesh, Brazil, Ethiopia, India, Thailand, the United Kingdom, and the United States were pooled. Test performance was assessed in a retrospective analysis on capillary and venous specimens. All study sites used spectrophotometry for reference G6PD testing, and either the HemoCue or complete blood count for reference hemoglobin measurement. The sensitivity of the STANDARD G6PD Test using the manufacturer thresholds for G6PD deficient and intermediate cases in capillary specimens from 4212 study participants was 100% (95% Confidence Interval (CI): 97.5%-100%) for G6PD deficient cases with 60% on the reference assay. The negative predictive value for females with G6PD activity >60% was 99.6% (95% CI 99.1%-99.8%) on capillary specimens. Sensitivity among 396 P. vivax malaria cases was 100% (69.2%-100.0%) for both deficient and intermediate cases. Across the full dataset, 37% of those classified as G6PD deficient or intermediate resulted from true normal cases. Despite this, over 95% of cases would receive correct treatment with primaquine, over 87% of cases would receive correct treatment with tafenoquine, and no true G6PD deficient cases would be treated inappropriately based on the result of the STANDARD G6PD Test. CONCLUSIONS: The STANDARD G6PD Test enables safe access to drugs which are contraindicated for individuals with G6PD deficiency. Operational considerations will inform test uptake in specific settings.

Background The 8-aminoquinolines, primaquine and tafenoquine, are the only available drugs for the radical cure of Plasmodium vivax hypnozoites. Previous evidence suggests that there is dose-dependent 8-aminoquinoline induced methaemoglobinaemia and that higher methaemoglobin concentrations are associated with a lower risk of P. vivax recurrence. We undertook a systematic review and individual patient data meta-analysis to examine the utility of methaemoglobin as a population-level surrogate endpoint for 8-aminoquinoline antihypnozoite activity to prevent P. vivax recurrence. Methods and findings We conducted a systematic search of Medline, Embase, Web of Science, and the Cochrane Library, from 1 January 2000 to 29 September 2022, inclusive, of prospective clinical efficacy studies of acute, uncomplicated P. vivax malaria mono-infections treated with radical curative doses of primaquine. The day 7 methaemoglobin concentration was the primary surrogate outcome of interest. The primary clinical outcome was the time to first P. vivax recurrence between day 7 and day 120 after enrolment. We used multivariable Cox proportional-hazards regression with site random-effects to characterise the time to first recurrence as a function of the day 7 methaemoglobin percentage (log base 2 transformed), adjusted for the partner schizonticidal drug, the primaquine regimen duration as a proxy for the total primaquine dose (mg base/kg), the daily primaquine dose (mg/kg), and other factors. The systematic review protocol was registered with PROSPERO (CRD42023345956). We identified 219 P. vivax efficacy studies, of which 8 provided relevant individual-level data from patients treated with primaquine; all were randomised, parallel arm clinical trials assessed as having low or moderate risk of bias. In the primary analysis data set, there were 1,747 patients with normal glucose-6-phosphate dehydrogenase (G6PD) activity enrolled from 24 study sites across 8 different countries (Indonesia, Brazil, Vietnam, Thailand, Peru, Colombia, Ethiopia, and India). We observed an increasing dose-response relationship between the daily weight-adjusted primaquine dose and day 7 methaemoglobin level. For a given primaquine dose regimen, an observed doubling in day 7 methaemoglobin percentage was associated with an estimated 30% reduction in the risk of P. vivax recurrence (adjusted hazard ratio = 0.70; 95% confidence interval [CI] [0.57, 0.86]; p = 0.0005). These pooled estimates were largely consistent across the study sites. Using day 7 methaemoglobin as a surrogate endpoint for recurrence would reduce required sample sizes by approximately 40%. Study limitations include the inability to distinguish between recrudescence, reinfection, and relapse in P. vivax recurrences. Conclusions For a given primaquine regimen, higher methaemoglobin on day 7 was associated with a reduced risk of P. vivax recurrence. Under our proposed causal model, this justifies the use of methaemoglobin as a population-level surrogate endpoint for primaquine antihypnozoite activity in patients with P. vivax malaria who have normal G6PD activity., Author(s): Ihsan Fadilah 1,2,*, Robert J. Commons 3,4,5, Nguyen Hoang Chau 6, Cindy S. Chu 2,7, Nicholas P. J. Day 2,8, Gavin C. K. W. Koh 9, Justin A. Green [...]

All Plasmodium cases have declined over the last decade in northwestern Thailand along the Myanmar border. During this time, Plasmodium vivax has replaced Plasmodium falciparum as the dominant species. The decline in P. falciparum has been shadowed by a coincidental but delayed decline in P. vivax cases. This may be due to early detection and artemisinin-based therapy, species-specific diagnostics, and bed net usage all of which reduce malaria transmission but not P. vivax relapse. In the absence of widespread primaquine use for radical cure against P. vivax hypnozoites, the decline in P. vivax may be explained by decreased hypnozoite activation of P. vivax relapses triggered by P. falciparum. The observed trends in this region suggest a beneficial effect of decreased P. falciparum transmission on P. vivax incidence, but elimination of P. vivax in a timely manner likely requires radical cure.

We previously described a novel Plasmodium vivax invasion mechanism into human reticulocytes via the PvRBP2a-CD98 receptor-ligand pair. Using linear epitope mapping, we assessed the PvRBP2a epitopes involved in CD98 binding and recognized by antibodies from patients who were infected. We identified 2 epitope clusters mediating PvRBP2a-CD98 interaction. Cluster B (PvRBP2a431-448, TAALKEKGKLLANLYNKL) was the target of antibody responses in humans infected by P vivax. Peptides from each cluster were able to prevent live parasite invasion of human reticulocytes. These results provide new insights for development of a malaria blood-stage vaccine against P vivax. [ABSTRACT FROM AUTHOR]

Measurement of optimum treatment efficacy to address language delays in children using cochlear implants is difficult, but important, to promote evidence-based treatments and reduce treatment inequities. This exploratory retrospective study investigated associations between; frequency of early intervention (weekly, fortnightly, monthly); total dose (calculated in hours over a year); and child involvement in family activities on language outcomes for 42 pediatric cochlear implant recipients enrolled in aural/oral programs. Parents who attended the Cochlear Implant Clinic completed the Family and Educational Characteristics Questionnaires (FamEd-Q) at each post-operative review, and their children completed formal language assessments. Family and child demographic characteristics were collated. Children whose parents reported lower doses (in hours) of early intervention demonstrated better expressive language skills than children who received more intervention, but this result was confounded by other underlying differences between groups regarding age-at-first-implant and cognitive function. Additionally, children from families with greater relative socio-economic advantage tended to receive more frequent intervention sessions. Of practical significance, greater levels of child involvement in family activities were associated with higher child language scores.

A major strength of the guild approach is its ability to simplify community analysis by aggregating species with similar roles or functions into groups. These groups can be used to study a number of important ecological concepts, including functional diversity, community response to disturbance, and food-web dynamics. Despite increased use, guild membership can be based on subjective criteria that are arbitrarily chosen, leading to inconsistencies across studies. Additionally, studies using the guild approach generally ignore ontogenetic changes in diet and habitat use and therefore do not fully capture the complexity of aquatic communities. Although these issues have been discussed in the literature, much has changed since the last review was published a decade ago. In our examination, we discuss data requirements and consequences of data availability and reliability on guild formation. We identify bootstrapping and permutation techniques developed to address limitations through cluster validation and the identification of ontogenetic shifts prior to guild delineation. Lastly, we provide a step-by-step guide to guild analysis, accompanied by a decision tree, to facilitate objective and informed guild creation. Une des grandes forces de l'approche basee sur les guildes est sa capacite de simplifier l'analyse de communautes en regroupant les especes qui occupent des roles ou fonctions semblables. Ces groupes peuvent etre utilises pour etudier differents concepts ecologiques importants, dont la diversite fonctionnelle, la reaction de communautes a des perturbations et la dynamique de chaines trophiques. Malgre son utilisation croissante, le regroupement en guildes peut reposer sur des criteres subjectifs choisis de maniere arbitraire, menant ainsi a des incoherences entre etudes. Les etudes faisant appel a l'approche des guildes ne tiennent en outre generalement pas compte de variations ontogenetiques du regime alimentaire et de l'utilisation de l'habitat et ne capturent donc pas toute la complexite des communautes aquatiques. Bien que ces questions aient deja ete abordees, beaucoup de choses ont change depuis la derniere synthese publiee il y a une decennie. Dans notre examen, nous abordons les exigences en matiere de donnees et les consequences de la disponibilite et de la fiabilite des donnees sur la formation de guildes. Nous relevons des techniques d'amorcage et de permutation developpees pour aplanir des contraintes en recourant a la validation de regroupements et a l'identification de changements ontogeniques prealablement a la delimitation des guildes. Enfin, nous presentons un guide par etapes pour l'analyse par guildes, accompagne d'un arbre decisionnel, pour faciliter la formation objective et eclairee de guildes. [Traduit par la Redaction], Introduction In recent decades, the consideration of functional ecology has grown increasingly common in studies of aquatic ecosystems and other ecological disciplines (e.g., plant, insect, and avian ecology; McGill et [...]

The objective of this project was to document and increase vaccine coverage in migrant school children on the Thailand-Myanmar border. Migrant school children (n = 12,277) were enrolled in a school-based immunization program in four Thai border districts. The children were evaluated for vaccination completion and timing, for six different vaccines: Bacille Calmette-Guerin (BCG); Oral Polio vaccine (OPV); Hepatitis B vaccine (HepB); Diphtheria, Pertussis and Tetanus vaccine (DTP); Measles Containing Vaccine or Measles, Mumps and Rubella vaccine (MMR); Tetanus and Diphtheria containing vaccine (Td). Vaccine coverage proportions for BCG, OPV3, DTP3, HepB3 and measles containing vaccine were 92.3, 85.3, 63.8, 72.2, and 90.9 % respectively. Most children were able to receive vaccines in a time appropriate manner. School-based immunization programs offer a suitable vaccine delivery mechanism for hard-to-reach populations. However, these data suggest overall low vaccine coverage in migrant populations. Further efforts toward improving appropriate vaccine coverage and methods of retaining documentation of vaccination in mobile migrant populations are necessary for improved health.

As the global human population grows, it remains a top priority for communities, managers, policymakers, and stakeholders to maintain healthy, sustainable, and productive fisheries under continued global change. Here we used a dataset consisting of fish and lake characteristics for 536 lakes across Ontario, Canada, to test whether multiple climate, human, and biological factors differentially affect fish production (i.e., population biomass per hectare per year). We tested the hypothesis that temperature is the key driver of fisheries production by testing for the effects of multiple factors on the production of three top predatory fish species: cold-water lake trout (Salvelinus namaycush), cool-water walleye (Sander vitreus), and warm-water smallmouth bass (Micropterus dolomieu). Using boosted regression tree analyses, we found that lake trout production was most influenced by the volume of hypolimnetic habitat, walleye production was related to other climatic variables, and smallmouth bass production was most influenced by sampling day of the year followed by Secchi depth. Our results suggest that current fish production models--that only include temperature and body size--may oversimplify important ecological complexities and thus misinform management decisions because species respond differently to environmental drivers. Pour faire face a la croissance demographique mondiale, les communautes, gestionnaires, decideurs et parties prenantes doivent continuer de prioriser le maintien de ressources halieutiques saines, durables et productives dans un contexte de changements climatiques. Nous avons utilise un ensemble de donnees constitue de caracteristiques de poissons et de lacs pour 536 lacs en Ontario (Canada) pour verifier si divers facteurs climatiques, humains et biologiques exercent differents effets sur la production de poissons (c.-a-d. la biomasse de la population par hectare par annee). Nous avons verifie l'hypothese voulant que la temperature soit le principal facteur qui module la production des peches en examinant les effets de differents facteurs sur la production de trois especes de predateurs de niveau trophique superieur, a savoir le touladi (Salvelinus namaycush), une espece d'eau froide, le dore jaune (Sander vitreus), une espece d'eau fraiche, et l'achigan a petite bouche (Micropterus dolomieu), une espece d'eau chaude. En utilisant des analyses par arbre de regression augmente, nous constatons que le volume des habitats hypolimnetiques exerce la plus forte influence sur la production des touladis, que la production de dores jaunes est associee a d'autres variables climatiques et que la date d'echantillonnage, suivie de la profondeur mesuree par le disque de Secchi, influencent le plus la production d'achigans a petite bouche. Nos resultats donnent a penser que les modeles de production de poissons actuels, qui n'integrent que la temperature et la taille du corps, pourraient trop simplifier d'importantes complexites ecologiques et ainsi produire des decisions de gestion non optimales decoulant du fait que les especes ne repondent pas toutes de la meme maniere a differents facteurs environnementaux. [Traduit par la Redaction], Introduction The global human population is expected to reach 9.7 billion by the year 2050 (United Nations 2019), which will put continued stress on our freshwater ecosystems and the services [...]

Mutations in the glucose-6-phosphate dehydrogenase (G6PD) gene result in red blood cells with increased susceptibility to oxidative damage. Significant haemolysis can be caused by primaquine and other 8-aminoquinoline antimalarials used for the radical treatment of Plasmodium vivax malaria. The distribution and phenotypes of mutations causing G6PD deficiency in the male population of migrants and refugees in a malaria endemic region on the Thailand-Myanmar border were characterized. Blood samples for G6PD fluorescent spot test (FST), G6PD genotyping, and malaria testing were taken from 504 unrelated males of Karen and Burman ethnicities presenting to the outpatient clinics. The overall frequency of G6PD deficiency by the FST was 13.7%. Among the deficient subjects, almost 90% had the Mahidol variant (487G>A) genotype. The remaining subjects had Chinese-4 (392G>T), Viangchan (871G>A), Açores (595A>G), Seattle (844G>C) and Mediterranean (563C>T) variants. Quantification of G6PD activity was performed using a modification of the standard spectrophotometric assay on a subset of 24 samples with Mahidol, Viangchan, Seattle and Chinese-4 mutations; all samples showed a residual enzymatic activity below 10% of normal and were diagnosed correctly by the FST. Further studies are needed to characterise the haemolytic risk of using 8-aminoquinolines in patients with these genotypes.