Rapid Result Test On Track to Transform Sickle Cell Disease Screening for Millions

Soon after birth, a baby in the United States is tested for sickle cell disease, the often-devastating genetic blood disorder affecting more than 100,000 Americans and 20 million of people worldwide. If positive, that newborn typically begins a course of treatment that can greatly prolong life and help stave off complications of the disease. But in sub-Saharan Africa, where the majority of sickle cell disease cases can be found—and where resources are scant—newborn screening programs are virtually non-existent, and as a result, so is treatment that could save lives.

Now, research shows that with a new rapid result test kit, a diagnosis of sickle cell disease may no longer be a death sentence for children in the most affected parts of the world.

HemoTypeSC, a dipstick-type test, is relatively inexpensive, accurate, and can provide timely diagnosis of sickle cell disease, according to the study published in the American Journal of Hematology. The test has the potential to be a game-changer for people with the disease who live in distressed areas around the world.

“Children with sickle cell disease have down to a 10 percent chance of reaching their fifth birthday if they are not diagnosed and get treatment early in life,” said Erik Serrao, Ph.D., a study author who also is the HemoTypeSC project manager at Silver Lake Research Corporation, the Los Angeles-based diagnostic company that developed the test. “That is why it’s extremely important to screen for the disease at birth or within the first year of life.”

Current gold-standard clinical methods for diagnosing sickle cell disease require laboratory equipment, a continuous electrical supply, a dedicated operating staff, about 1 mL of whole blood from each patient, and the ability to transport blood samples from where they were collected to possibly distant testing facilities. While it is often impossible to meet these standards in many parts of sub-Saharan Africa, the diagnostic tests patients do have access to still present problems: They are costly, and often it takes weeks or months before results come back to the families.

Silver Lake Research developed HemoTypeSC to address these challenges. With a Phase 2 Small Business Innovation Research grant from the National Heart, Lung and Blood Institute (NHLBI) in 2017, Serrao and his colleagues took HemoTypeSC into the real world for evaluation after years of product development.

HemoTypeSC uses simple technology—test strips—similar to a pregnancy test. The strips contain specific proteins that, in a few simple steps and after a short waiting period, can detect normal and abnormal hemoglobin proteins in whole blood.

In sickle cell disease, abnormal hemoglobin proteins cannot deliver oxygen to the body’s tissues due to defective hemoglobin S and C genes. The end result are sickled shape red blood cells and a cascade of complications such as sudden, severe pain known as pain crises.

The test can also detect the sickle cell trait, which shows up in someone who inherits one hemoglobin S or C and one normal hemoglobin A gene. While the sickle cell trait typically does not result in symptoms or complications from the disease, it is important for couples who are planning to have children to speak with a health professional who can explain the risk of having a child with sickle cell disease. The test does not require sophisticated laboratory equipment, electricity, refrigeration, or highly trained personnel.

To evaluate its effectiveness in people living in low-, medium-, and high-resourced environments, the team tested HemoTypeSC in study centers in Techiman, Ghana; in Martinique, part of the Caribbean Islands; and in Cincinnati, OH. Using a single drop of blood from each of the 587 participants—newborns, children, and adults across the three centers—the HemoTypeSC test correctly identified those with and without sickle cell disease and sickle cell trait in almost all of the cases.

One family in Ghana, for example, learned that their premature baby had sickle-hemoglobin C disease and would have been sent home, undiagnosed, shortly after birth had it not been for the test. Such findings, Serrao said, suggest that HemoTypeSC could set the standard for sickle cell disease testing of newborns, as well as for children at immunization age, across Africa.

Obiageli Nnodu, professor of hematology and blood transfusion and director of the Center of Excellence for Sickle Cell Disease Research and Training at the University of Abuja, has recently published findings on the effectiveness of HemoTypeSC and other similar sickle cell disease rapid tests in Nigeria. While the results add to a growing body of evidence, the test may be prone to human error when reading, interpreting and validating test results.

Nnodu is also the Nigeria principal investigator of the Sickle Pan-African Consortium, or SPARCO. The NHLBI-funded consortium currently works to address the burden of sickle cell disease in five African countries, with the development of a database being one of several objectives. Working with existing programs, SPARCO will contribute to the research infrastructure needed to reduce the burden of sickle cell disease across the continent.

“Although newborn screening for sickle cell disease is not a primary SPARCO activity, babies and infants with a sickle cell disease who were diagnosed through our newborn screening program could eventually be enrolled in the registry upon parental consent,” said Nnodu. “These babies could also be part of SPARCO’s implementation studies that focus on preventing infection and administering hydroxyurea, a medicine that can reduce sickle cell disease complications.”

Serrao acknowledged that one limitation of HemoTypeSC is its inability to detect hemoglobin D, E, and O, which are common in some parts of the Middle East and Southeast Asia. While this is also a limitation of other sickle cell screening devices, Serrao said users of HemoTypeSC in regions with a high prevalence of these hemoglobin variants should keep this limitation in mind.

Meanwhile, Serrao said he and his colleagues are focused on bringing HemoTypeSC to as many people as possible, including those living in Europe and its territories, where the test is already approved. The test was recently approved by the Kenya Pharmacy & Poisons Board and the National Agency for Food & Drug Administration & Control in Nigeria, with registration by the Ghanaian Food and Drugs Authority expected to imminently follow. In-depth field validations have been conducted thus far in Uganda and Nigeria, with further evaluation underway in other African countries and India. And in the United States, where Serrao said the test could be helpful at blood banks that need to screen new and archived blood samples, HemoTypeSC is awaiting approval.

“HemoTypeSC can help both children and adults afflicted with sickle cell disease,” Serrao said. “Once these young people are identified with the disease, they can be put on medication and become healthy, happy, and extremely productive members of society.”

Disclaimer

Reference to any specific commercial products, process, service, manufacturer, and/or company does not constitute an endorsement or recommendation by the National Heart, Lung, and Blood Institute (NHLBI), the NHLBI's Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs, or any other portion of the U.S. Government.