Implementation of a Sickle Cell Disease Screening Initiative in Uganda with HemoTypeSC^TM

Sickle Cell Disease (SCD) is a widely prevalent hemoglobinopathy in sub-Saharan Africa that is frequently deadly in early life, killing 70-80% of afflicted children before their fifth birthday. SCD accounts for ~20% of annual childhood deaths in Uganda - one of the first African countries surveyed for SCD prevalence. This health danger is currently addressable: prophylactic intervention programs including hydroxyurea, antibiotics, and immunizations have drastically reduced SCD mortality in developed areas and could be implemented in sub-Saharan Africa in a cost-effective manner. However, the cornerstone of such programs, newborn diagnostic screening, has not been widely implemented in Uganda, or elsewhere in Africa. This dilemma springs from the cost and logistical problems with accepted diagnostic methodologies, which require laboratory equipment, highly-trained operating personnel, uninterrupted electrical supply, and sample transport away from the point-of-care (POC). Clearly, a low-cost, low-complexity, POC diagnostic test for SCD could help diminish this public health crisis.

HemoTypeSC^TM is an inexpensive competitive lateral-flow immunoassay that uses monoclonal antibodies to detect hemoglobins (Hbs) A, S, and C in a 1.5-μL droplet of whole blood. In this study we conducted a field validation of HemoTypeSC accuracy in children of southeastern Uganda, aimed at providing evidence for the applicability of the test in widespread newborn screening programs in the region. This study was designed as a blinded, prospective diagnostic accuracy trial of HemoTypeSC as an investigational test compared to Hb electrophoresis as a reference method. Jinja Regional Referral Hospital was selected as a low-resource study center due to its relatively high daily patient volume, as well as its suitability as a prototype center for organized newborn SCD screening within Uganda.

Exactly 1,000 children five years old and younger were prospectively recruited from the hospital wards and outpatient clinics. HemoTypeSC was compared to Hb electrophoresis for detection of the Hb phenotypes HbAA (normal), HbAS (sickle cell trait), and HbSS (SCD). Initial data analysis indicated that HemoTypeSC correctly identified 998 out of 1,000 phenotypes, for an overall accuracy of 99.8%. This included 720/720 (100%) specimens correctly identified as HbAA, 182/182 (100%) correctly identified as HbAS, and 96/98 (98%) correctly identified as HbSS. The two discordant samples were both identified as HbSS by electrophoresis and HbAS by HemoTypeSC. To resolve these discrepancies, the patients with the discordant HbSS/HbAS results were recalled for repeat testing. During the ensuing phone contact for scheduling, it was discovered that both individuals were in fact previously diagnosed with SCD, and both had been recently transfused. The previous diagnostic result reports for these participants were subsequently viewed and confirmed as HbSS. Because HbA was indeed present in the blood of these two patients at the time of sampling, the HbAS result was determined to be true. A secondary data analysis was therefore conducted, in which these two specimens were included as true positives for HbSS and true negatives for HbAS. It was ultimately determined that HemoTypeSC correctly identified 1,000 out of 1,000 phenotypes across all patients screened, including 96/96 HbSS specimens, for an overall sensitivity, specificity, positive predictive value, and negative predictive value of 100%.

These results indicate that HemoTypeSC performs at least as accurately as the gold-standard method of Hb electrophoresis in detecting SCD and sickle cell trait at the POC in a resource-limited setting. This to our knowledge represents the first ever report of a rapid test for SCD displaying 100% sensitivity and specificity in a field validation study.

In summary, HemoTypeSC represents a promising tool that can presently enable newborn and general population screening. Widespread combination of HemoTypeSC newborn and population screening programs with appropriate treatment, prophylaxis, and health counseling systems in countries most affected by the disease could save the lives of millions of children over the coming decades.

A separate abstract regarding a HemoTypeSC field validation trial in Nigeria has also been submitted as a late-breaking abstract. We would be open to sharing a presentation slot with this group.