Cincinnati Children's Research Foundation.

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Background The Uganda Sickle Surveillance Study provided evidence for a large sickle burden among HIV‐exposed infants in Uganda. To date, however, no large scale screening program has been developed for Central or East Africa. Methods A 3‐year targeted sickle cell screening project in Uganda was designed by the Ministry of Health to (1) determine sickle cell trait and disease prevalence within high‐burden districts, (2) document the prevalence among HIV‐exposed and nonexposed children, (3) confirm previously suggested HIV comorbidity, and (4) estimate the co‐inheritance of known genetic modifiers of sickle cell disease. Results A total of 163 334 dried blood spot samples collected between April 2015 and March 2018 were analyzed, including 112 352 samples within the HIV Early Infant Diagnosis program. A high burden with >1% sickle cell disease was found within targeted East Central and Mid‐Northern districts, in both HIV‐exposed and nonexposed children. Based on crude birth‐rate data, 236 905 sickle cell trait births and 16 695 sickle cell disease births will occur annually in Uganda. Compared to sickle cell disease without HIV, the odds ratio of having sickle cell disease plus HIV was 0.50 (95% confidence interval = 0.40‐0.64, P < .0001). Alpha‐thalassemia trait and G6PD deficiency were common with sickle cell disease, but with different geospatial distribution. Conclusions High sickle cell burden and potential HIV comorbidity are confirmed in Uganda. Genetic modifiers are common and likely influence laboratory and clinical phenotypes. These prospective data document that targeted sickle cell screening is feasible and effective in Uganda, and support development of district‐level comprehensive care programs.

Key Points Five Hb variants were identified in the Uganda Sickle Surveillance Study with nonuniform distribution across the country. Recognition of IEF patterns and molecular techniques provide an algorithm for the diagnosis of hemoglobin variants in sub-Saharan Africa.

objective Sickle cell disease is an important public health issue that is increasingly recognised as a substantial contributor to morbidity and early childhood mortality in sub-Saharan Africa. We aimed to provide information from large-scale, long-term sickle cell screening efforts in Africa. methods We used nationally representative data from the centralised public health laboratory database in Uganda to examine epidemiological trends in sickle cell screening over a five-year period, comparing age and geographic adjustments to prevalence among different testing cohorts of children aged 0-24 months, and calculating screening coverage within high-burden districts. results A total of 324 356 children aged 0-24 months were screened for sickle cell trait and disease from February 2014 to March 2019. A high national burden of sickle cell disease (0.9%) was confirmed among a cohort of samples co-tested with HIV. In the cohort of samples referred specifically for sickle cell testing, the overall prevalence of sickle cell disease was 9.7% and particularly elevated in high-burden districts where focused screening occurred. The majority of children were screened before age 4 months, but the sickle-specific cohort had a larger proportion of affected children tested between age 5-9 months, coincident with onset of disease signs and symptoms. Successful screening coverage of sickle cell disease births was achieved in several high-burden districts. conclusions Examination and analysis of national sickle cell screening trends in Uganda documents the successes of focused screening strategies as an important step towards universal screening. With this evidence and increased healthcare provider knowledge, Uganda can optimise sickle cell diagnosis and management across the country.

Objective To determine the regional- and district-level newborn prevalence of sickle cell trait and disease, and the prevalence of haemoglobin variants and genetic modifiers of sickle cell disease, in the nine regions of north-western United Republic of Tanzania. Methods We repurposed dried blood spot samples from children (aged 0–24 months) born to mothers living with human immunodeficiency virus (HIV), collected as part of the HIV Early Infant Diagnosis programme, for sickle cell diagnosis. We performed isoelectric focusing to determine whether samples had normal haemoglobin, sickle cell trait, sickle cell disease or a rare haemoglobin variant. We shipped samples diagnosed as disease or variant to Cincinnati Children’s Hospital in the United States of America for deoxyribonucleic-acid-based analyses to determine the prevalence of α-thalassaemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency or fetal haemoglobin genetic modifiers. Findings We analysed a total of 17 200 specimens during February 2017–May 2018. We observed a prevalence of sickle cell trait and disease of 20.3% (3492/17 200) and 1.2% (210/17 200), respectively. District-level trait varied from 8.6% (5/58) to 28.1% (77/274). Among confirmed sickle cell disease specimens, we noted 42.7% (61/143) had 1-gene deletion and 14.7% (21/143) had 2-gene deletion α-thalassaemia trait. We documented G6PD A – deficiency in 19.2% (14/73) of males. Conclusion Our calculated prevalence is twice as high as previously reported and reinforces the need for enhanced sickle cell diagnostic services. Our district-level data will inform public health policy, allowing screening and disease-modifying hydroxyurea therapy to be focused on high-prevalence areas, until universal newborn screening is available.

Program fundraising efforts included an annual Buganda Kingdom Fun Run and Outreach screening events. c World Sickle Cell Day celebration was held on June 19. Post-US3 screening resultsTargeted screening of high-burden districts c 112 352 samples were tested from 2015 to 2018 (Table 1).cThe prevalence of SCT (15.5%) and SCD (1.3%) was higher than in the original US3 study.