Sickle cell disease (SCD), a non-communicable disease, has its highest burden in Sub Saharan Africa and is the most frequent genetic haemoglobinopathy, with over 300 000 children born with the disease annually and this number is expected to increase to 400 000 by 2050 (1–3). The majority of these children (50–90%), die before their 5th birthday with approximately 150,000–300,000 annual SCD child deaths in Africa ,which can potentially accounting for 5–10% of the region’s total child mortality (1, 4, 5). Nearly 90% of SCD patients live in 3 countries, Nigeria, India and Democratic Republic of Congo. In these countries nearly 2% of the population have SCD with a carrier rate, sickle cell trait, ranging from 10–30% (6). However, it has been found recently that the distribution of all the hemoglobin disorders is extremely diverse within different countries, even within small geographical distances (7).
Sickle cell disease (SCD) is a genetic autosomal recessive disorder which results from substitution of valine for glutamine at position 6 of the beta chain haemoglobin. The haemoglobin (HbSS) tetramer that results from the substitution has alpha 2 and beta S2, is poorly soluble and rigid when deoxygenated resulting in vaso-occlusion which in turn causes several complications (8). Moreover, there are different forms of sickle cell disease which include HbSS, HbSC, HbS beta thalassaemia, HbSE, and HbSD and many more and it occurs throughout sub-Saharan Africa, and in small pockets in the Mediterranean region, the Middle East and Indian subcontinent (9). The HbSC disease is restricted to parts of west and North Africa, HbS thalassemia is localised in parts in sub-Saharan Africa, some parts of the Middle East and India subcontinent. Additionally, HbSE occur commonly in India, Bangladesh, Myammer and east and southeast Asia (9).
Among SCD variants, HbSS is the commonest in the sub-Saharan region and is associated with severe forms of complications in comparison with the other variants. These complications include but are ,not limited to priapism, pulmonary emboli, osteonecrosis, and ultimately damages every organ system including the spleen, retinae, kidneys and liver(10).
Sickle cell trait the heterozygous form of HbS is the carrier state for sickle cell haemoglobin. These individuals inherit HbS/C from one parent and HbA from the other parent making them heterozygous (HbAS) or HbAC. More than 100 million or about 5% of the world population have the sickle cell trait (SCT) (11). Most people with sickle cell trait live asymptomatically. Despite SCT being perceived as an asymptomatic condition several case reports and reviews reported an increased incidence of renal medullary carcinoma among young patients with SCT with the age wide from 9 to 69 years (12–14). Other forms of SCT include HbAC, and HbAE although these are rare forms (9).
The gene for sickle hemoglobin (HbS) is a prime example of natural selection. It is generally believed that its current prevalence in many tropical populations reflects selection for the carrier form (sickle cell trait (HbAS) through a survival advantage against death from malaria (15). A study by Williams et al, 2005 (15) showed that HbAS had no effect on the prevalence of symptomless parasitaemia but was 50% protective against mild clinical malaria, 75% protective against admission to the hospital for malaria, and almost 90% protective against severe or complicated malaria.
Malaria remains a major public health problem in Namibia mostly in Kavango East and West, Ohangwena and Zambezi regions. The 4 regions accounted for 96% of cases with Kavango East and West accounting for 81%, Zambezi 10% and Ohangwena 5% according to a recently published study (2023) by Katale and Gemechu(16).
Early detection of sickle cell disease or trait is imperative to the long term outcome as treatment can be initiated early. In developed countries, newborn screening (NBS) has been shown to improve survival of children with sickle cell disease with under 5 childhood mortality reduced 10 fold due to interventions done before development of complications (17).
Over the years, several techniques have been employed to diagnose and monitor SCD. High performance liquid chromatography (HPLC and isoelectric focusing( IEF) are the two main laboratory techniques for haemoglobinopathy screening currently suitable for routine use and have been used in developed countries and several studies in Africa (18). Molecular genetic tests are considered the gold standard tests as they target the affected genes and are able to distinguish the different mutations (19). These include Restriction Fragment Polymorphism (RFLP) partial restriction of deoxyribonucleic acid (DNA), Real-time polymerase chain reaction (PCR) (20) and DNA sequencing which is the most expensive molecular method compared to RFLP and PCR
because of reagents, instrumentation, personnel and review time required for analysis, but it provides the most comprehensive data for beta-globin gene (20). Point of care tests (POCT), SCD screening methods validated in developing countries, are easier to perform and require less qualified personnel with results available within a short period of time(21). These tests provide results within a short period of time. Sickle cell SCAN™, a lateral flow assay reliably identifies HbA, HbS, and HbC, easily performed by non-skilled personnel, easily interpreted, rapid test at the point of care (21). This test detected the correct A, S, and C presence with an overall diagnostic accuracy of 99% at the bedside (22). However it is relatively more expensive than other POCTs.
Other novel POCTs include Heme Cheap, which is reliable, able to distinguish most types of sickle cell disease including compound heterozygotes. However, it requires skilled interpretation, web-based, automated and this is out of reach of most resource limited regions (21). Additionally, Aqueous multiphase System (AMPS) (density based test to separate Hb in different density fluids) and Paper based Sickle test (microfluid assessment) are inexpensive and require non-skilled personnel. However, the interpretation maybe difficult and the later requires a scanner for interpretation (21, 23).
Lately, HemoTypeSC™, a POCT a monoclonal antibody based which targets Hb A, S, and C but not Hb F is one of the newest techniques yield results in 10 minutes (24, 25). Multiple studies found HemoTypeSC™ to have a sensitivity and specificity of over 98% compared to the gold standard methods of HPLC and IEF (22, 26–31). Success in implementation of newborn screening programs include health education of stake holders (32). The HemotypeSC point-of-care testing device has shown high sensitivity and specificity for diagnosing sickle cell disease (SCD) in various studies. A study by Olatunya et al, 2021 found that HemotypeSC had perfect concordance with PCR and 100% accuracy in diagnosing SCD, while Nnodu et al, 2019 reported a sensitivity of 93.4% and a specificity of 99.9% for SCD (26, 33). In addition, Okeke, 2022 further demonstrated the feasibility of using dried blood spots with HemotypeSC, with a sensitivity and specificity of 100% compared to the standard test (31). A further study by Adegoke et al 2022,(34) also found high sensitivity of HemotypeSC when compared to alkaline cellulose acetate hemoglobin electrophoresis. These findings collectively suggest that HemotypeSC is a reliable and accurate tool for SCD diagnosis. Although other POCT test such as Sickle SCAN have been validated in some parts, Hemotype SC has shown to be cheaper and easy to use (35, 36).
New born screening for sickle cell disease is not yet established in Namibia. Sick children present to referral hospitals with SCD related complications prior to diagnosis. Birth prevalence of sickle cell disease and sickle cell trait have not been documented in Namibia.
The aim of the study was to determine the birth prevalence of sickle cell disease and sickle cell trait using the point of care test HemotypeSC™. Haemoglobin AA was considered normal, HbSS, HbC (HbSC), sickle cell disease whilst heterozygous for HbS/ HbC, HbAS / HbAC sickle cell trait. This study was the first in Namibia to carry out NBS for sickle cell disease and first to use the point of care test HemotypeSC™. In addition the study will guide policy on the need to introduce SCD, NBS in Namibia as recommended by the World Health Organisation (WHO) African Region strategy which provides a set of public health interventions to reduce the burden of SCD in African. The strategy focuses on improved awareness, disease prevention and early detection (37).