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IntroductionScreening 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 FindingsData 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. Negative predictive values for females with G6PD activity >60% was 99.6% (95% CI 99.1%–99.8%) on capillary specimens. Test sensitivity among 396P. vivaxmalaria cases was 100% (69.2%–100.0%) for both deficient and intermediate cases. In the study population, a high proportion of those classified as G6PD deficient or intermediate resulted from true normal cases. Despite this, the majority cases would receive the correct medication and no true G6PD deficient cases would be treated inappropriately.ConclusionsThe 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.

BackgroundReliable tools to inform outpatient management of childhood pneumonia in resource-limited settings are needed. We investigated the value added by biomarkers of host infection response to the performance of the Liverpool quick Sequential Organ Failure Assessment score (LqSOFA), for triage of children presenting with pneumonia to a primary care clinic in a refugee camp on the Thailand-Myanmar border.Methods900 presentations of children aged ≤ 24 months meeting WHO pneumonia criteria were included. The primary outcome was receipt of supplemental oxygen. We compared discrimination of a clinical risk score (LqSOFA) to markers of endothelial injury (Ang-1, Ang-2, sFlt-1), immune activation (CHI3L1, IP-10, IL-1ra, IL-6, IL-8, IL-10, sTNFR-1, sTREM-1), and inflammation (CRP, PCT), and quantified the net-benefit of including biomarkers alongside LqSOFA. We evaluated the differential contribution of LqSOFA and host biomarkers to the diagnosis and prognosis of severe pneumonia.Results49/900 (5.4%) presentations met the primary outcome. Discrimination of LqSOFA and Ang-2, the best performing biomarker, were comparable (AUC 0.82 [95% CI 0.76-0.88] and 0.81 [95% CI 0.74-0.87] respectively). Combining Ang-2 with LqSOFA improved discrimination (AUC 0.91; 95% CI 0.87-0.94; p < 0.001), and resulted in greater net-benefit, with 10-30% fewer children requiring oxygen supplementation incorrectly identified as safe for community-based management. Ang-2 had greater prognostic utility than LqSOFA to identify children requiring supplemental oxygen later in their illness course.ConclusionsCombining Ang-2 and LqSOFA could guide referrals of childhood pneumonia from resource-limited community settings. Further work on integration into patient triage is required.

BackgroundAccurate and reliable guidelines for referral of children from resource-limited primary care settings are lacking. We identified three practicable paediatric severity scores (Liverpool quick Sequential Organ Failure Assessment [LqSOFA], quick Pediatric Logistic Organ Dysfunction-2 [qPELOD-2], and the modified Systemic Inflammatory Response Syndrome [mSIRS]) and externally validated their performance in young children presenting with acute respiratory infections to a primary care clinic located within a refugee camp on the Thailand-Myanmar border.MethodsThis secondary analysis of data from a longitudinal birth cohort study consisted of 3,010 acute respiratory infections in children aged ≤ 24 months. The primary outcome was receipt of supplemental oxygen. We externally validated the discrimination, calibration, and net-benefit of the scores, and quantified gains in performance that might be expected if they were deployed as simple clinical prediction models, and updated to include nutritional status and respiratory distress.Results104/3,010 (3.5%) presentations met the primary outcome. The LqSOFA score demonstrated the best discrimination (AUC 0.84; 95% CI 0.79-0.89) and achieved a sensitivity and specificity > 0.80. Converting the scores into clinical prediction models improved performance, resulting in ∼20% fewer unnecessary referrals and ∼30-60% fewer children incorrectly managed in the community.ConclusionsThe LqSOFA score is a promising triage tool for young children presenting with acute respiratory infections in resource-limited primary care settings. Where feasible, deploying the score as a simple clinical prediction model might enable more accurate and nuanced risk stratification, increasing applicability across a wider range of contexts.

IntroductionNew point-of-care (POC) quantitative G6PD testing devices developed to provide safe radical cure for P. vivax malaria may be used to diagnose G6PD deficiency in newborns at risk of severe neonatal hyperbilirubinaemia, improving clinical care, and preventing related morbidity and mortality. Methods: We conducted a mixed-methods study analyzing technical performance and usability of the “STANDARD G6PD” Biosensor when used by trained midwives on cord blood samples at two rural clinics on the Thailand-Myanmar border.ResultsIn 307 cord blood samples, the Biosensor had a sensitivity of 1.000 (95%CI 0.859-1.000) and a specificity of 0.993 (95% CI 0.971-0.999) as compared to gold standard spectrophotometry to diagnose G6PD deficient newborns using a receiving operator characteristic (ROC) analysis-derived threshold of ≤4.8IU/gHb. The Biosensor had a sensitivity of 0.727 (95%CI: 0.498-0.893) and specificity of 0.933 (95%CI: 0.876-0.969) for 30-70% activity range in females using ROC analysis-derived range of 4.9 to 9.9IU/gHb. These thresholds allowed identification of all G6PD deficient neonates and 80% of female neonates with intermediate phenotypes.Need of phototherapy treatment for neonatal hyperbilirubinaemia was higher in neonates with deficient and intermediate phenotypes as diagnosed by either reference spectrophotometry or Biosensor.Focus group discussions found high levels of learnability, willingness, satisfaction, and suitability for the Biosensor in this setting. The staff valued the capacity of the Biosensor to identify newborns with G6PD deficiency early (“We can know that early, we can counsel the parents about the chances of their children getting jaundice”) and at the POC, including in more rural settings (“Because we can know the right result of the G6PD deficiency in a short time. Especially for the clinic which does not have a lab”). Conclusions: The Biosensor is a suitable tool in this resource-constrained setting to identify newborns with abnormal G6PD phenotypes at increased risk of neonatal hyperbilirubinaemia.

Targeted malaria elimination strategies require highly sensitive tests to detect low density malaria infections (LDMI). Commonly used methods for malaria diagnosis such as light microscopy and antigen-based rapid diagnostic tests (RDTs) are not sensitive enough for reliable identification of infections with parasitaemia below 200 parasites per milliliter of blood. While targeted malaria elimination efforts on the Thailand-Myanmar border have successfully used high sample volume ultrasensitive quantitative PCR (uPCR) to determine malaria prevalence, the necessity for venous collection and processing of large quantities of patient blood limits the widespread tractability of this method. Here we evaluated a real-time quantitative reverse transcription PCR (qRT-PCR) method that significantly reduces the required sample volume compared to uPCR. To do this, 304 samples collected from an active case detection program in Kayin state, Myanmar were compared using uPCR and qRT-PCR. Plasmodium spp. qRT-PCR confirmed 18 of 21 uPCR Plasmodium falciparum positives, while P. falciparum specific qRT-PCR confirmed 17 of the 21 uPCR P. falciparum positives. Combining both qRT-PCR results increased the sensitivity to 100% and specificity was 95.1%. These results show that malaria detection in areas of low transmission and LDMI, can benefit from the increased sensitivity of qRT-PCR especially where sample volume is limited.

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.