Implementing newborn screening for sickle cell disease as part of immunisation programmes in Nigeria: a feasibility study.

BACKGROUND: Sickle cell disease is highly prevalent in sub-Saharan Africa, where it accounts for substantial morbidity and mortality. Newborn screening is paramount for early diagnosis and enrolment of affected children into a comprehensive care programme. Up to now, this strategy has been greatly impaired in resource-poor countries, because screening methods are technologically and financially intensive; affordable, reliable, and accurate methods are needed. We aimed to test the feasibility of implementing a sickle cell disease screening programme using innovative point-of-care test devices into existing immunisation programmes in primary health-care settings. METHODS: Building on a routine immunisation programme and using existing facilities and staff, we did a prospective feasibility study at five primary health-care centres within Gwagwalada Area Council, Abuja, Nigeria. We systematically screened for sickle cell disease consecutive newborn babies and infants younger than 9 months who presented to immunisation clinics at these five centres, using an ELISA-based point-of care test (HemoTypeSC). A subgroup of consecutive babies who presented to immunisation clinics at the primary health-care centres, whose mothers gave consent, were tested by the HemoTypeSC point-of-care test alongside a different immunoassay-based point-of-care test (SickleSCAN) and the gold standard test, high-performance liquid chromatography (HPLC). FINDINGS: Between July 14, 2017, and Sept 3, 2019, 3603 newborn babies and infants who presented for immunisation were screened for sickle cell disease at five primary health-care centres using the ELISA-based point-of-care test. We identified 51 (1%) children with sickle cell anaemia (HbSS), four (<1%) heterozygous for HbS and HbC (HbSC), 740 (21%) with sickle cell trait (HbAS), 34 (1%) heterozygous for HbA and HbC (HbAC), and 2774 (77%) with normal haemoglobin (HbAA). Of the 55 babies and infants with confirmed sickle cell disease, 41 (75%) were enrolled into a programme for free folic acid and penicillin, of whom 36 (88%) completed three visits over 9 months (median follow-up 226 days [IQR 198-357]). The head-to-head comparison between the two point-of-care tests and HPLC showed concordance between the three testing methods in screening 313 newborn babies, with a specificity of 100% with HemoTypeSC, 100% with SickleSCAN, and 100% by HPLC, and a sensitivity of 100% with HemoTypeSC, 100% with SickleSCAN, and 100% by HPLC. INTERPRETATION: Our pilot study shows that the integration of newborn screening into existing primary health-care immunisation programmes is feasible and can rapidly be implemented with limited resources. Point-of-care tests are reliable and accurate in newborn screening for sickle cell disease. This feasibility study bodes well for the care of patients with sickle cell disease in resource-poor countries. FUNDING: Doris Duke Charitable Foundation, Imperial College London Wellcome Trust Centre for Global Health Research, and Richard and Susan Kiphart Family Foundation.

Sickle cell disease in southwestern Nigeria: assessment of knowledge of primary health care workers and available facilities.

Background: Patients with sickle cell disease (SCD) benefit optimally from comprehensive care. In Nigeria, despite the huge burden, involvement of community health workers (CHWs) in the management of SCD is poor. Methods: This community-based study assessed SCD-related knowledge of 182 CHWs from the 46 primary health care (PHC) centres in Ilesa, southwestern Nigeria. Available facilities and management practices for SCD care at these centres were also evaluated using pretested self-administered questionnaires and observational checklists. Results: The majority of CHWs (167/182 [91.8%]) knew that SCD is an inheritable blood disorder. However, only 32.4% and 26.4% knew that SCD can be diagnosed in the prenatal and neonatal periods, respectively. Also 37.4%, 49.5% and 67.6% knew about the role of chemoprophylaxis (folic acid/penicillin), adequate fluids and malaria prevention, respectively, in SCD care. Overall, 37.9% had good knowledge on the nature and care of the disease. Just 2/46 (4.3%) PHC centres treat patients with SCD. SCD-targeted nutritional counselling and referral to secondary/tertiary hospitals were poor and unorganized. No centre offered SCD screening, home visits or recordkeeping. Conclusions: The level of SCD care and knowledge of CHWs at PHC centres in southwestern Nigeria of early SCD diagnosis and crisis prevention is poor. CHWs should be regularly trained and equipped for basic SCD management, including early detection, crisis prevention, prompt referral and provision of basic genetic counselling, to dispel associated myths and stigma.

Comparative study of the growth and nutritional status of Brazilian and Nigerian school-aged children with sickle cell disease.

Background: Comparative studies of patients in different sociogeographic/ecological zones may unravel potential environmental and nutritional factors influencing disease phenotype. In sickle cell disease (SCD), differential access to comprehensive care may influence their growth and nutritional status. Methods: From June 2015 to February 2016, steady-state nutritional parameters of 109 Brazilian and 95 Nigerian children with SCD attending routine clinic visits at Universidade Federal de São Paulo, Brazil and Obafemi Awolowo University Teaching Hospital, Ile-Ife (Ilesa unit), respectively, were compared. Results: A relatively high proportion of the children in both centres (23.5%) were wasted [body-mass index (BMI)-for-age z-score<-2). BMI-for-age z-score, height-for-age z-score, upper arm fat area and fat percentage were lower in the Nigerian cohorts. More Nigerians, 29.5% (28/95) against 18.3% (20/109) were wasted, and had short stature, [12.6% (12/95) vs. 3.7% (4/109)] than Brazilians. A higher proportion of Brazilian patients were overweight or obese (9.2 vs. 4.3%), and taller for age (15.6 vs. 8.4%). None of the Nigerian patients had severe vitamin D deficiency, only 12.6% (12/95) had suboptimal vitamin D and 1.1% (1/95) had low serum zinc levels, unlike 79.8% (87/109) of the Brazilian patients with suboptimal vitamin D and 10.1% (11/109) with low zinc. Conclusion: Undernutrition is still prevalent among the two cohorts. Nigerian patients were thinner and had reduced linear growth for age. This observation justifies the continued need for specialized nutritional care for children with SCD. In addition to hydroxyurea therapy, research is needed to determine appropriate nutritional intervention and exercise regimens for these children.

Relationship between serum 25-hydroxyvitamin D and inflammatory cytokines in paediatric sickle cell disease.

BACKGROUND: Alteration in the concentration of inflammatory cytokines may contribute to pathogenesis in sickle cell anaemia (SCA). Vitamin D may suppress pro-inflammatory cytokines and enhance anti-inflammatory cytokines. OBJECTIVE: To compare steady state levels of pro-and anti-inflammatory cytokines of Nigerian SCA children with age- and sex-matched healthy controls, and determine the relationship with 25-hydroxyvitamin-D (25-OHD). Effects of three months of vitamin D supplementation on cytokines of SCA children with suboptimal 25-OHD were also evaluated. METHODS: Serum 25-OHD, IL-1ß, 2, 6, 8, 11, 12, 13, 17, 18 of 95 SCA children and 75 matched controls were determined using HPLC. The 12 SCA children with suboptimal 25-OHD received 2000IU of vitamin D daily for 3months, and their post supplementation cytokines and 25-OHD levels were compared with the baseline values. RESULTS: IL-2, 6, 8, 12, 17 and 18 were higher in SCA children than the controls (p≤0.001), but no significant variation in IL-11 and 13 (p=0.131 and 0.057 respectively). Patients with suboptimal serum 25-OHD had higher IL-6, 8 and 18 (p=0.003, 0.010 and 0.002 respectively) and lower levels of IL-11 (p=0.005). Significant positive treatment effects were observed: post-supplementation, serum 25-OHD increased by 23.3ng/mL, p<0.001; proinflammatory cytokines IL-2, 6, 8, 17 and 18 (p<0.001) were reduced and anti-inflammatory cytokine IL-11 was increased, p<0.001. CONCLUSIONS: Suboptimal 25OHD is associated with enhanced levels of pro-inflammatory markers in children with SCA. Three months of daily vitamin D supplementation reversed the trend. Hence; Vitamin D supplementation may reduce the inflammatory milieu and serve as an anti-inflammatory agent in the management of SCA.