Is integrating sickle cell disease and HIV screening logical?
Authors: Stephen Obaro
Journal: The Lancet Global Health (2016)

Sickle cell disease is the most prevalent genetic disorder worldwide, with burden being highest in countries with constrained resources and endemic malaria. With very poor survival in children and severe morbidity in older survivors, the health-care infrastructures in the worst-affected parts of the world are overwhelmed. Diagnosis is frequently made only when complications occur, and supportive care is commonly poor.1Chakravorty S Williams TN Sickle cell disease: a neglected chronic disease of increasing global health importance.Arch Dis Child. 2015; 100: 48-53Crossref PubMed Scopus (93) Google Scholar In contrast, in several developed countries with much lower prevalence, neonatal screening has become the norm, and has led to institution of early preventive and supportive care that have substantially improved outcomes. In The Lancet Global Health, Grace Ndeezi and colleagues2Ndeezi G Kiyaga C Hernandez AG et al.Burden of sickle cell trait and disease in the Uganda Sickle Surveillance Study (US3): a cross-sectional study.Lancet Glob Health. 2016; (published online Jan 28.)http://dx.doi.org/10.1016/S2214-109X(15)00288-0Google Scholar report the Uganda Sickle Surveillance Study (US3), done in collaboration with Cincinnati Children's Hospital Medical Center, OH, USA, which used a simple but innovative approach to screening infants (younger than 18 months) for sickle cell trait and disease. They used residual dried blood spots collected for the Early Infant Diagnosis programme for HIV in ten regions (112 districts) of the country and used isoelectric focusing analysis of haemoglobin to calculate prevalence. 99 243 samples were screened, with results available from 97 631. The overall prevalence of sickle cell trait ranged from 4·6% to 19·8% and for disease from 0·2% to 1·5%. Sickle cell disease was less prevalent among children older than 12 months than among younger children (0·6% vs 0·8% in children aged 0–6·0 months and 0·7% in children aged older than 6·0 to 12·0 months) and in those with comorbid HIV than in those negative for HIV (0·5% vs 0·8%). The national prevalence of haemoglobin variants was 0·5% (range across regions 0·1–1·8). Although high and variable frequencies of sickle cell trait in different ethnic groups in Uganda have been reported previously,3Lehmann H Rapper AB Distribution of the sickle-cell trait in Uganda, and its ethnological significance.Nature. 1949; 164: 494Crossref PubMed Scopus (20) Google Scholar those data were from around 70 years ago and were based on small sample sizes. Thus, the findings of Ndeezi and colleagues provide a contemporary overview that is nationally representative. While the genesis of the S mutation is well recognised as a secondary factor to the endemicity of malaria and natural selection, the time is ripe to begin to address the genesis of new variants and their importance. The children assessed in US3 were enrolled in the Early Infant Diagnosis programme for HIV screening and did not provide consent to be tested for sickle cell disease, a genetic disorder. Furthermore, the results were communicated to the families but optimum clinical care could not be assured. The ethical justification for this study could be debated, as it is unlikely that it would have been permissible in most developed countries, where the use of residual neonatal dried blood spots for research purposes has been challenged.4Bayefsky MJ Saylor KW Berkman BE Parental consent for the use of residual newborn screening bloodspots: respecting individual liberty vs ensuring public health.JAMA. 2015; 314: 21-22Crossref PubMed Scopus (9) Google Scholar Nevertheless, the Ugandan Government and Ministry of Health deserve commendation for making an important decision in favour of public health. This study provides an excellent example of a meaningful integration of screening programmes to provide useful data for health planning that could be emulated by other countries in sub-Saharan Africa, where sickle cell is highly prevalent and early infant diagnosis programmes are in place. Much too often in these countries, ministries of health partner with foreign donors to run several parallel programmes that are expensive and sometimes counterproductive. 23 (0·5%) of 5080 children with HIV assessed by Ndeezi and colleagues also had sickle cell disease, compared with 693 (0·8%) of 92 024 who were HIV negative. This finding suggests early mortality in children with comorbid sickle cell disease and HIV, and should be studied further. Several case reports suggest that sickle cell disease slows the progression of HIV,5Owusu ED Visser BJ Nagel IM Mens PF Grobusch MP The interaction between sickle cell disease and HIV infection: a systematic review.Clin Infect Dis. 2015; 60: 612-626Crossref PubMed Scopus (17) Google Scholar, 6Nouraie M Nekhai S Gordeuk VR Sickle cell disease is associated with decreased HIV but higher HBV and HCV comorbidities in U.S. hospital discharge records: a cross-sectional study.Sex Transm Infect. 2012; 88: 528-533Crossref PubMed Scopus (28) Google Scholar for which several hypotheses have been proposed that might offer new leads for HIV treatments.5Owusu ED Visser BJ Nagel IM Mens PF Grobusch MP The interaction between sickle cell disease and HIV infection: a systematic review.Clin Infect Dis. 2015; 60: 612-626Crossref PubMed Scopus (17) Google Scholar, 6Nouraie M Nekhai S Gordeuk VR Sickle cell disease is associated with decreased HIV but higher HBV and HCV comorbidities in U.S. hospital discharge records: a cross-sectional study.Sex Transm Infect. 2012; 88: 528-533Crossref PubMed Scopus (28) Google Scholar, 7Obaro S Does sickle cell disease protect against HIV/AIDS?.Sex Transm Infect. 2012; 88: 533Crossref PubMed Scopus (7) Google Scholar Almost all these reports, however, involved patients with horizontal infection. What happens in infants who acquire infection vertically and have sickle cell disease remains unclear and warrants exploration, for which there cannot be a better natural platform than where both disorders are highly prevalent. The introduction of early diagnosis of sickle cell disease in African countries would provide a unique opportunity to assess the interaction between this disorder and HIV. The time for a worldwide concerted effort to control sickle cell disease is long overdue. Although technical support can be provided by partners in developed countries, as was the case in US3,2Ndeezi G Kiyaga C Hernandez AG et al.Burden of sickle cell trait and disease in the Uganda Sickle Surveillance Study (US3): a cross-sectional study.Lancet Glob Health. 2016; (published online Jan 28.)http://dx.doi.org/10.1016/S2214-109X(15)00288-0Google Scholar the ultimate and long-term care of patients remains the prerogative of the host country. African countries and leaders, therefore, must own up to this responsibility, improve funding allocation for supporting care, and use appropriate media to promote public awareness and strategies to reduce incidence. Finally, the goal of preventing early death in people with sickle cell disease in sub-Saharan Africa goes well beyond neonatal screening. In Brazil, such screening has not been associated with a substantial decline in early mortality.8Sabarense AP Lima GO Silva LM Viana MB Survival of children with sickle cell disease in the comprehensive newborn screening programme in Minas Gerais, Brazil.Paediatr Int Child Health. 2015; (published online Feb 23.)http://dx.doi.org/10.1179/2046905515Y.0000000001Google Scholar Thus, while early diagnosis is logical, what is more important is to provide good care afterwards, otherwise a neonatal screening programme could easily become another way of increasing the existing pool of people known to be affected by sickle cell disease. I declare no competing interests. Burden of sickle cell trait and disease in the Uganda Sickle Surveillance Study (US3): a cross-sectional studyPrevalence of sickle cell trait and disease were high in Uganda, with notable variation between regions and districts. The data will help to inform national strategies for sickle cell disease, including neonatal screening. Full-Text PDF Open Access