The high cost, complexity and reliance on electricity, specialized equipment and supplies associated with conventional diagnostic methods limit the scope and sustainability of newborn screening for sickle cell disease (SCD) in sub-Saharan Africa and other resource-limited areas worldwide. Here we describe the development of a simple, low-cost, rapid, equipment- and electricity-free paper-based test capable of detecting sickle hemoglobin (HbS) in newborn blood samples with a limit of detection of 2% HbS. We validated this newborn paper-based test in a cohort of 159 newborns at an obstetric hospital in Cabinda, Angola. Newborn screening results using the paper-based test were compared to conventional isoelectric focusing (IEF). The test detected the presence of HbS with 81.8% sensitivity and 83.3% specificity, and identified SCD newborns with 100.0% sensitivity and 70.7% specificity. The use of the paper-based test in a two-stage newborn screening process could have excluded about 70% of all newborns from expensive confirmatory testing by IEF, without missing any of the SCD newborns in the studied cohort. This study demonstrates the potential utility of the newborn paper-based test for reducing the overall cost of screening newborns for SCD and thus increasing the practicality of universal newborn SCD screening programs in resource-limited settings.

Intermittent or uneven daily dosing of hydroxyurea is as effective as fixed daily doses in treating SCA. This strategy may enable treatment of additional children with SCA in SSA.

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Newborn screening for sickle cell disease (SCD) in developing countries is limited by the cost and technical complexity of current screening methodologies and the delayed availability of screening results. We have recently developed a rapid diagnostic test for SCD that can quickly and inexpensively identify blood samples containing hemoglobin S. We hypothesized that our rapid test would be practical for use in a resource-limited setting in Cabinda, Angola, and that screening mothers or neonates for the presence of hemoglobin S in blood samples would be an effective means of identifying neonates at high risk of having sickle cell disease prior to more definitive testing. After informed consent, we collected blood samples heel-stick from neonates and by finger-stick from mothers at the primary obstetric hospital in Cabinda. We then tested these samples by the rapid SCD test and scored them by visual assessment of staining patterns. Neonates were scored as positive (HbS detected) or negative (no HbS detected) and mothers as AA, AS (sickle trait), or SS (sickle cell disease). Neonatal samples were subsequently tested by isoelectric focusing (IEF) electrophoresis to determine exact sickle cell status. In a cohort of 133 mother-neonate pairs, we used rapid testing on maternal samples to categorize neonates as high-risk (mother positive for HbS) or low-risk (mother negative for HbS). The rapid test was highly accurate in identifying neonates who could be excluded from IEF testing, with a negative predictive value of 93% (Figure 1). In a cohort of 95 neonates similarly triaged by rapid testing on neonatal samples, the negative predictive value of the test was 96% (Figure 2). In both cohorts, the one neonate with HbSS disease was successfully triaged into the high-risk group. Maternal screening with the rapid test would have reduced the proportion of neonates requiring confirmatory IEF testing to 19%, while neonatal screening would have reduced this proportion to 26%. These results indicate the potential utility of the rapid diagnostic test as a screening tool prior to more definitive testing. Used in combination with confirmatory IEF, our rapid test could significantly decrease the cost of newborn screening for SCD and increase its clinical utility by permitting more rapid identification of affected infants. Disclosures Piety: Halcyon Biomedical: Patents & Royalties: Mr. Piety is a co-inventor on a utility PCT application, "Paper-based diagnostic test" (PCT/US2012/064856, 11/13/2012), claiming priority benefit of U.S. 61/692,994 (8/24/2012) and U.S. 61/558,009 (11/10/2011). . Shevkoplyas:Halcyon Biomedical: Equity Ownership, Patents & Royalties: Co-inventor on a utility PCT application, "Paper-based diagnostic test" (PCT/US2012/064856, 11/13/2012), claiming priority benefit of U.S. 61/692,994 (8/24/2012) and U.S. 61/558,009 (11/10/2011). Part-owner of Halcyon Biomedical Inc.,.