Newborn Screening for Sickle Cell Anemia and Sickle Variant Syndromes in Kampala, Uganda

Background: In much of the developed world, newborn screening identifies infants with sickle cell disease (SCD), and allows implementation of simple, cost-effective interventions that decrease morbidity and mortality. The burden of SCD is dispropotionally high in sub-Saharan Africa, and newborn screening programs are generally in their pilot stage. They face many challenges in implementation, and practices that work in developed countries are often not feasible in low-resource environments. This is a systematic review of newborn screening programs that have been conducted in sub-Saharan Africa, with a focus on diagnostic modalities.

Methods: We searched PubMed with wide criteria in order to capture all relevant studies, essentially searching for all papers with “sickle” and a sub-Saharan African country mentioned in their abstract or keywords. The inclusion criteria was subjects tested at birth or within the first 28 days of life. A 2015 systematic review by Piel et al. “Observed and expected frequencies of structural hemoglobin variants in newborn screening surveys in Africa and the Middle East: deviations from Hardy-Weinberg equilibrium” supplemented our search.

Results: Our search yielded 2310 references. These references were assessed first by title and abstract, then 236 papers were perused for inclusion. In the end, 18 papers fit our inclusion criteria. Of these 18, only Ghana had a screening program longer than 2 years and supported by the government. Eleven studies used isoelectric focusing (IEF) as their primary diagnostic method. Only 8 studies performed screening with the intent to enroll affected infants into care. Sickling tests, electrophoresis, high performance liquid chromatography (HPLC) and PCR are explored in relation to these studies.

Discussion: Cellulose agar electrophoresis (CAE) and acid citrate electrophoresis, IEF, and HPLC are appropriate diagnostic modalities that have been utilized for large volume newborn SCA screens. IEF and HPLC offer improved sensitivity over CAE, and are both acknowledged to have almost 100% sensitivity for common hemoglobin variants. Overall, families showed high acceptability of testing their newborns. A challenge common for the pilots were funding and contacting affected families with results. While IEF was seen to be the most commonly used diagnostic modality, details as to challenges faced and involved costs were rarely discussed. As shared knowledge will increase the success of these programs, details surrounding the complicated logistics behind newborn testing and results reporting are important to include.