Comparison of prescribing restrictions for primaquine and tafenoquine under three different scenarios broken down by gender.

<p>This assumes that 10% of heterozygous females would test deficient at screens with a 30% activity threshold, and 70% of heterozygous females and 5% of all wild type individuals at a 70% threshold. Top left: current proportions of individuals ineligible for radical cure for vivax malaria following G6PD deficiency testing; top right: proportions of individuals ineligible for radical cure if primaquine and tafenoquine could be given to females breast-feeding infants older than 1 month; bottom left: proportions of individuals ineligible for radical cure if primaquine could be given to G6PD deficient persons.</p

Comparison of estimated treatment coverage for primaquine (blue) and tafenoquine (red) under the three main scenarios considered in this paper.

<p>i) current prescribing restrictions (thick lines); ii) 8-aminoquinolines given to G6PD normal lactating women with infants older than 1 month (dashed lines); iii) alternative primaquine regimen for G6PD deficient individuals (dotted line).</p

Distribution of G6PD activities in wild type males (determined from phenotype) and wild type females (only those determined from genotype to avoid bias from heterozygotes).

<p>Each activity has been scaled by 10/(Study median activity) to obtain a global median of 10. The units are relative to the corresponding study median. The 70% of population median threshold is shown by the vertical dashed red line.</p

Validation of the quantitative point-of-care CareStart biosensor for assessment of G6PD activity in venous blood

<div><p>Introduction</p><p>Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy in the human population affecting an estimated 8% of the world population, especially those living in areas of past and present malaria endemicity. Decreased G6PD enzymatic activity is associated with drug-induced hemolysis and increased risk of severe neonatal hyperbilirubinemia leading to brain damage. The G6PD gene is on the X chromosome therefore mutations cause enzymatic deficiency in hemizygote males and homozygote females while the majority of heterozygous females have an intermediate activity (between 30–80% of normal) with a large distribution into the range of deficiency and normality. Current G6PD qualitative tests are unable to diagnose G6PD intermediate activities which could hinder wide use of 8-aminoquinolines for <i>Plasmodium vivax</i> elimination. The aim of the study was to assess the diagnostic performances of the new Carestart G6PD quantitative biosensor.</p><p>Methods</p><p>A total of 150 samples of venous blood with G6PD deficient, intermediate and normal phenotypes were collected among healthy volunteers living along the north-western Thailand-Myanmar border. Samples were analyzed by complete blood count, by gold standard spectrophotometric assay using Trinity kits and by the latest model of Carestart G6PD biosensor which analyzes both G6PD and hemoglobin.</p><p>Results</p><p>Bland-Altman comparison of the CareStart normalized G6PD values to that of the gold standard assay showed a strong bias in values resulting in poor area under-the-curve values for both 30% and 80% thresholds. Performing a receiver operator curve identified threshold values for the CareStart product equivalent to the 30% and 80% gold standard values with good sensitivity and specificity values, 100% and 92% (for 30% G6PD activity) and 92% and 94% (for 80% activity) respectively.</p><p>Conclusion</p><p>The Carestart G6PD biosensor represents a significant improvement for quantitative diagnosis of G6PD deficiency over previous versions. Further improvements and validation studies are required to assess its utility for informing radical cure decisions in malaria endemic settings.</p></div

Two-way sensitivity analysis results showing the impact of changes in the level of adherence to primaquine regimens.

<p>Green represents disability-adjusted life-years (DALYs) averted by the screening strategy for a cohort of 1000 individuals. For costs, yellow indicates increased costs and blue indicates cost savings for the screening strategy for one individual. For net monetary benefit (<i>NMB</i>), purple indicates scenarios where the screening strategy would be cost-effective at a threshold of US$500 (<i>T</i>) where <i>NMB = T × ΔDALYs– ΔCosts</i>.</p

Demographic and clinical characteristics of children at enrolment according to treatment (AQ+SP: amodiaquine+sulphadoxine-pyrimethamine; CD+A chlorproguanil-dapsone+artesunate) and presence of the G6PD (A-) deficiency allele (hemizygous males, homozygous and heterozygous females).

<p>Demographic and clinical characteristics of children at enrolment according to treatment (AQ+SP: amodiaquine+sulphadoxine-pyrimethamine; CD+A chlorproguanil-dapsone+artesunate) and presence of the G6PD (A-) deficiency allele (hemizygous males, homozygous and heterozygous females).</p

CareStart G6PD biosensor.

<p>The device consolidates a hemoglobin measurement device (on the left) with a G6PD activity measurement device (on the right). Two disposables and samples are therefore required, one of each analyte measurement. The device then calculates the G6PD activity normalized for hemoglobin concentration based on the two measurements.</p

The table shows simulated outcomes for 1000 <i>P</i>. <i>vivax</i> malaria patients of undetermined G6PD status at attendance, if they were managed according to each of three strategies (chloroquine, primaquine and screening) according to G6PD status, treatment given and the test result if screened.

<p>The table shows simulated outcomes for 1000 <i>P</i>. <i>vivax</i> malaria patients of undetermined G6PD status at attendance, if they were managed according to each of three strategies (chloroquine, primaquine and screening) according to G6PD status, treatment given and the test result if screened.</p

Costs and disability adjusted life year (DALY) results over one year per primary episode treated in the base case analysis and probabilistic sensitivity analysis (PSA).

<p>All costs are in 2014 United States Dollars.</p

Area under the curve for ROC analysis at different activity thresholds for the reference test and CareStart biosensor.

<p>Area under the curve for ROC analysis at different activity thresholds for the reference test and CareStart biosensor.</p