Every year across the globe, more than 7 million infants are born with either a congenital abnormality or a genetic disease.1 Sickle cell disease (SCD) is the world's most prevalent genetic disorder and poses the largest public health threat, particularly in sub-Saharan Africa (SSA) where more than 300,000 infants with sickle cell anemia (SCA) are born each year. This translates to 821 births per day or 34 births every hour.2,3 Nearly 90 percent of all those born with SCD in SSA will die before age five years simply because there is no access to universal newborn screening.4 Early detection of genetic diseases such as SCD during infancy allows each child to benefit from simple lifesaving interventions such as anti-infection prophylaxis and parental education about potential life-threatening complications such as severe anemia from splenic sequestration.5
In countries like the United States where newborn screening has been well established and universal across all states since 2006, the typical methods used (hemoglobin [Hgb] electrophoresis, isoelectric focusing, high-performance liquid chromatography [HPLC], and sickle solubility testing) present common challenges to adaptation in resource-poor settings. They either require high levels of technical expertise and specialized equipment to deploy or are time and/or labor intensive — factors that contribute to a significantly higher relative cost of implementation.
Recently, inexpensive point-of-care (POC) qualitative strategies to detect hemoglobinopathies have been developed.6 Both the HemoTypeSC™ (Silver Lake Research, Azusa, CA) ELISA-based test and the SickleSCAN™ test (BioMedomics, Mooresville, NC) based on lateral flow immunoassay have shown fidelity in field testing. Both POC tests report more than 99 percent diagnostic accuracy and specificity in field conditions for detecting the presence of Hgb A, S, and C.6,7 The advantages of POC testing for hemoglobinopathies include its low cost relative to other established methods; diminished need for technical expertise, specialized equipment, and even electricity; and short turnaround time for obtaining results. These advantages make POC methods ideal for deployment in primary care and public health settings where population level follow-up may be challenging. Purists may argue that these POC tests are unable to provide quantitative measurements of the amount of each identified Hgb variant and therefore provide less specific diagnostic information, and furthermore cannot be used to monitor treatment efficacy (with either hydroxyurea or transfusions). Another critique of POC testing is that it does not detect Hgb variants other than types A, S, or C; therefore, the tests will likely miss uncommon variants. While this is true, the known epidemiology of Hgb variants in SSA favors the predominance of Hgb SS and SC; thus, this should be the primary focus of screening efforts.
Prof. Obiageli E. Nnodu and colleagues conducted a prospective cohort study on the implementation of newborn screening for SCD in Nigeria. To optimize feasibility, they embedded this study within the national immunization program, leveraging existing public health systems, staff, and infrastructure already established at five local primary health care centers. All consecutive 3,603 infants aged nine months and younger who presented for routine immunization visits between July 14, 2017, and September 3, 2019, were offered counseling and hemoglobinopathy screening using the HemoTypeSC POC test. A concurrent validation sample was obtained on all positive POC screens for central confirmation at the regional Federal Medical Center Newborn Screening Laboratory for North Central Nigeria in Keffi, Nasarawa State, using HPLC. Three hundred and thirteen infants also received POC testing using the SickleSCAN™ test to validate the use of POC in the primary care setting.
There was a 99 percent acceptance rate of newborn screening by the 400 mothers who participated in a qualitative survey. Results demonstrated a 77 percent prevalence of Hgb AA, 20.5 percent with sickle cell trait (Hgb AS), 0.9 percent with hemoglobin AC, and 2.4 percent with SCD (Hgb SS, 1.4%; Hgb SC, 0.1%). There was 100 percent concordance in results across all three testing modalities demonstrating 100 percent specificity and sensitivity between the HemoTypeSC™ POC, the HPLC confirmatory test, and SickleSCAN™ POC tests, respectively.
A newborn screening program must go beyond just obtaining the test, however. It should include a functional and supportive public health infrastructure that provides robust education and genetic counseling, a clear plan for short-term follow-up and confirmatory diagnosis when needed, a streamlined process for referral for ongoing clinical management, and program evaluation and long-term follow-up. Prof. Nnodu and colleagues successfully enrolled 81 percent of the infants detected by newborn screening into an SCD program where they received follow-up visits every three months and were provided prophylactic penicillin, folic acid supplementation, ongoing SCD specific anticipatory guidance, and information on how to access the sickle cell program for comprehensive care. Nineteen percent of families declined participation however, despite robust education and engagement efforts. This alludes to the need for ongoing implementation research to understand cultural and geographic barriers to newborn screening acceptance.
This pilot by Prof. Nnodu and colleagues clearly supports the feasibility of implementing a robust and coordinated newborn screening program using a less costly but highly sensitive and specific POC test by embedding this program within the existing Nigerian public health infrastructure. This model could be replicated across the country as well as across other resource-poor countries as an imperfect start toward the establishment of universal newborn screening in SSA. While imperfect, it is important to note that even in the U.S., universal newborn screening was not fully established across all states until 21 years after it was first initiated in New York State in 1975.
Rather than waiting for a perfect system, we applaud Prof. Nnodu and colleagues for embracing the words of Voltaire (as cited in his poem La Bégueule), “Dit que le mieux est l’ennemi du bien,” or “Don't let the best be the enemy of good,” and demonstrating the practical viability and benefit of POC for SCD in primary care. This pragmatic approach to implementing newborn screening in SSA is critical to early identification of even just a portion of the 821 infants born daily with SCA in SSA to offer them a chance of life beyond their fifth birthday.
Dr. Osunkwo indicated no relevant conflicts of interest.