Sickle cell disease is common throughout much of sub-Saharan Africa. It affects up to 3% of births in some areas and is associated with very high mortality.
Many cases go undiagnosed in regions where there are few resources, because standard methods for diagnosing the disease require sophisticated equipment and reliable electricity.
A new test that costs less than $2, requires only a small drop of blood, and can be performed in about 10 minutes could dramatically change the dynamics of sickle cell diagnosis in Africa, say researchers who developed the product.
“HemoTypeSC is an accurate, inexpensive, and rapid tool that can enable sickle cell disease screening programs across Africa and India,” explained study author Erik Serrao, PhD, director of business and product development at Silver Lake Research Corporation in Azusa, California, the manufacturer of the test. “It is easy to use with no reported issues with protocol or reading results.”
Serrao was talking here at the American Society of Hematology (ASH) 2018.
In a study he presented, HemoTypeSC correctly identified 998 of 1000 phenotypes, for an overall accuracy of 99.8%, in a cohort of 1000 young children. It is also suitable for routine newborn screening, he commented, citing a smaller study that involved about 60 babies.
Sickle Cell Disease Undiagnosed in Africa
Sickle cell disease accounts for 20% of annual childhood deaths in Uganda, which was one of the first countries in Africa to be surveyed to determine the prevalence of this disease.
Prophylactic intervention programs, which include treatment with hydroxyurea, antibiotics, and immunizations, have been implemented in developed regions of the world and have been shown to drastically reduce deaths from sickle cell disease.
These measures could also be used in sub-Saharan Africa in a cost-effective manner, but the problem in these regions is that the disease is often undiagnosed. Whereas in the United States, for example, newborns are screened for sickle cell disease, such screening has not been widely implemented in Uganda or elsewhere in Africa. “Most people with sickle cell are identified only after they come to the hospital with life-threatening symptoms,” Serrao said.
The current gold-standard diagnostic methods are sophisticated, requiring laboratory equipment and highly trained personnel to run the tests. Up-front investment and maintenance are needed, a large volume of blood is required, the cost per test is unaffordable to most, and the blood specimens and results must be shipped away from and then returned to the point of care.
In contrast, HemoTypeSC is an inexpensive lateral-flow immunoassay that uses monoclonal antibodies to detect hemoglobins (Hbs) A, S, and C in only a 1.5-μL droplet of whole blood. In this study, Serrao and colleagues conducted a field validation of the test’s accuracy in a cohort of 1000 children living in southeastern Uganda. The goal was to provide evidence to support use of the test in widespread newborn screening programs in the region. The accuracy of HemoTypeSC was compared to that of Hb electrophoresis, which served as a reference.
The majority of children (84.5%) were aged 5 years or younger; 19.7% were aged 1 month to 1 year, and 24.9% were aged from 1 to 2 years.
In the initial analysis, HemoTypeSC correctly identified 998 of 1000 phenotypes, for an overall accuracy of 99.8%. These included 720 of 720 specimens (100%) that were correctly identified as HbAA, 182 of 182 specimens (100%) correctly identified as HbAS, and 96 of 98 (98%) correctly identified as HbSS.
The two discordant samples were both identified as HbSS by electrophoresis but as HbAS by HemoTypeSC.
When the two patients were retested, however, it was disclosed that they had already been diagnosed with sickle cell disease and had recently undergone transfusion. Therefore, the children had both normal and sickle hemoglobin in their blood at the time of testing, and so the diagnosis with use of HemoTypeSC was in fact correct.
When a secondary analysis was conducted, the two discordant specimens were included as true positive specimens for HbSS and true negative specimens for HbAS. It was thus determined that HemoTypeSC correctly identified 1000 of 1000 phenotypes across all patients screened, for overall sensitivity, specificity, positive predictive value, and negative predictive value of 100%.
Serrao noted that one limitation of the study was that the test was not used for newborn screening, but a recent study in this setting showed that the HemoTypeSC test was 100% accurate.
Sickle cell screening programs can be cost-effective in Africa, Serrao said. He predicted that it “will actually save significant amounts of money for governments.
“Early screening plus treatment and counseling can save millions of lives over the coming decades,” he added.
Commenting on the new test at an ASH press briefing in which the study was highlighted, moderator Mark Crowther, MD, from McMaster University, Hamilton, Ontario, Canada, commented that the test would also be useful in the developed world. As an example, he said it could be performed on the spot for a patient who was admitted into the emergency department at 2 AM. Currently, testing would take at least a day and could be conducted only when laboratories were open.
HemoTypeSC is approved for sale in Europe, and the company hopes that the test will be approved across Africa and in India within the coming year.
The study was funded by Silver Lake Research Corporation, manufacturer of the test. Serrao is an employee of Silver Lake Research and no other disclosures were reported.