Demographic, malaria and G6PDd prevalence data by gender and ecosystem in western Sumba.

<p>n = sample number.</p><p>¹ Population number was obtained from central agency statistic from each district.</p><p>² Microscopy diagnosed.</p><p>³ One subject experienced mixed infection of <i>P</i>. <i>falciparum</i> and <i>P</i>. <i>vivax</i>.</p><p>⁴ Hb < 10 g/dl.</p><p>⁵ G6PD activities ≤4.6 U/gHb.</p><p>⁶ Samples screened as G6PD deficient but declined, absent or failed to be DNA extracted.</p><p>Demographic, malaria and G6PDd prevalence data by gender and ecosystem in western Sumba.</p

Impact of Hb level on G6PD activities.

<p>Blue line represents those samples having extremely high G6PD activity and some degree of anemia (R² = 0.08) and red line represents those having normal Hb level (R² = 0.48) and t-value = 28.6 (p<0.001).</p

Enzymatic parameters from purified G6PD from study subjects in western Sumba according to genotype.

<p>* median of the samples analyzed;</p><p>**cannot be calculated because the interval between the data are too small;</p><p>CI is confidence interval</p><p>Enzymatic parameters from purified G6PD from study subjects in western Sumba according to genotype.</p

Scatter plot showing the relationship between age and G6PD activity in Sumba.

<p>Scatter plot showing the relationship between age and G6PD activity in Sumba.</p

A) Schematic work flow of the study in western Sumba in 2012 and B) map of G6PD deficiency and malaria prevalences in study sites in Sumba.

<p>Small inlet showed the map of Indonesia and where Sumba island is located.</p

Scatter plot of G6PD activities of G6PD deficient and normal subjects from Trinity quantitative versus kinetics assays measured in U/g Hb.

<p>The different colours represented different variant (V in either normal, heterozygous and hemizygous mutants. VL Het, VC Het and CT Het represented heterozygous females having Vanua Lava, Viangchan and Chatham variant respectively. VL Hem, VC Hem and CT Hem represented hemizyogous males having Vanua Lava, Viangchan and Chatham variant respectively.</p

Assessment of Point-of-Care Diagnostics for G6PD Deficiency in Malaria Endemic Rural Eastern Indonesia

<div><p>Background</p><p>Patients infected by <i>Plasmodium vivax</i> or <i>Plasmodium ovale</i> suffer repeated clinical attacks without primaquine therapy against latent stages in liver. Primaquine causes seriously threatening acute hemolytic anemia in patients having inherited glucose-6-phosphate dehydrogenase (G6PD) deficiency. Access to safe primaquine therapy hinges upon the ability to confirm G6PD normal status. CareStart G6PD, a qualitative G6PD rapid diagnostic test (G6PD RDT) intended for use at point-of-care in impoverished rural settings where most malaria patients live, was evaluated.</p><p>Methodology/Principal Findings</p><p>This device and the standard qualitative fluorescent spot test (FST) were each compared against the quantitative spectrophotometric assay for G6PD activity as the diagnostic gold standard. The assessment occurred at meso-endemic Panenggo Ede in western Sumba Island in eastern Indonesia, where 610 residents provided venous blood. The G6PD RDT and FST qualitative assessments were performed in the field, whereas the quantitative assay was performed in a research laboratory at Jakarta. The median G6PD activity ≥5 U/gHb was 9.7 U/gHb and was considered 100% of normal activity. The prevalence of G6PD deficiency by quantitative assessment (<5 U/gHb) was 7.2%. Applying 30% of normal G6PD activity as the cut-off for qualitative testing, the sensitivity, specificity, positive predictive value, and negative predictive value for G6PD RDT versus FST among males were as follows: 100%, 98.7%, 89%, and 100% versus 91.7%, 92%, 55%, and 99%; P = 0.49, 0.001, 0.004, and 0.24, respectively. These values among females were: 83%, 92.7%, 17%, and 99.7% versus 100%, 92%, 18%, and 100%; P = 1.0, 0.89, 1.0 and 1.0, respectively.</p><p>Conclusions/Significance</p><p>The overall performance of G6PD RDT, especially 100% negative predictive value, demonstrates suitable safety for G6PD screening prior to administering hemolytic drugs like primaquine and many others. Relatively poor diagnostic performance among females due to mosaic G6PD phenotype is an inherent limitation of any current practical screening methodology.</p></div

Graphs illustrate diagnostic outcomes for the G6PD RDT (left) and FST (right) among males (top) and females (bottom) across quantitative G6PD activity values for each subject.

<p>A qualitative test classification as deficient is shown in red, and green for normal. Vertical lines within each identify specific diagnostic thresholds (10%, 20%, 30%, 60% and 100%) employed to calculate diagnostic performance characteristics.</p

Chart illustrating the rationale for assessing diagnostic performance of qualitative G6PD screening devices in the context of a clinical decision to offer or withhold primaquine therapy in patients with <i>P</i>. <i>vivax</i> malaria.

<p>Each classification (bold font top), clinical outcome (normal font middle), and risk or benefit (italics bottom) of diagnostic performance appears in each box of classification.</p

Photographs illustrating visual test outcomes for the G6PD RDT (top) and FST (bottom).

<p>For FST, samples were spotted at time 0, 5 and 10 minutes interval and the dark spots were considered deficient (D) and the bright ones were considered normal (N). RDT with purple color was considered normal (N) and no color was considered deficient (D).</p