High mortality from Plasmodium falciparum malaria in children living with sickle cell anemia on the coast of Kenya

Abstract

Although malaria is widely considered a major cause of death in young children born with sickle cell anemia (SCA) in sub-Saharan Africa, this is poorly quantified. We attempted to investigate this question through 4 large case-control analyses involving 7164 children living on the coast of Kenya. SCA was associated with an increased risk of admission to hospital both with nonmalaria diseases in general (odds ratio [OR] ‫؍‬ 4.17; 95% confidence interval [CI], 1.95-8.92; P < .001) and with invasive bacterial diseases in particular (OR ‫؍‬ 8.73; 95% CI, 4.51-16.89; P < .001). We found no evidence for a strongly increased risk of either uncomplicated malaria (OR ‫؍‬ 0.43; 95% CI, 0.09-2.10; P ‫؍‬ .30) or malaria complicated by a range of well-described clinical features of severity (OR ‫؍‬ 0.80; 95% CI, 0.25-2.51; P ‫؍‬ .70) overall; nevertheless, mortality was considerably higher among SCA than non-SCA children hospitalized with malaria. Our findings highlight both the central role that malaria plays in the high early mortality seen in African children with SCA and the urgent need for better quantitative data. Meanwhile, our study confirms the importance of providing all children living with SCA in malaria-endemic areas with effective prophylaxis. (Blood. 2010;116(10):1663-1668) IntroductionThe common causes of morbidity and mortality in children living with sickle cell anemia (SCA) in developed countries have been well documented through projects, such as the Cooperative Study of Sickle Cell Disease in the United States and the Jamaican Cohort study. Nevertheless, surprisingly little research has been conducted in Africa, 1-3 where more than 230 000 children with SCA, approximately 80% of the global burden, are born every year. 4 Although malaria is widely considered a major cause of death in African children with SCA, 1,5-7 this assumption is supported by surprisingly few data. Most reports have involved small, hospital-based studies and have lacked control data that enable comparisons of risk to be made with non-SCA subjects. 1 Perhaps the strongest evidence comes from the Garki project, conducted in northern Nigeria during the 1970s, which reported a nonsignificant trend toward higher survival of children with SCA in an area exposed to intensive malaria control. 8 However, studies suggesting that malaria is an important cause of death in children with SCA are balanced by others that show the opposite: children with SCA might even be less susceptible to malaria than those without the disease. 6,[9][10][11][12][13] Determining the true risk of death from malaria in subjects with SCA is important for several reasons. From a policy perspective, documenting an association between SCA and malaria death would provide strong justification for early-life SCA screening and the targeted prescription of effective malaria prophylaxis. Conversely, if the risk of malaria-specific death was not elevated, alternative approaches to prophylaxis and treatment might be considered. Recently, we reported that malaria was a rare cause...

Fever among Children with Sickle-Cell Disease: Findings from the General Pediatric Ward of the Owendo Pediatric Hospital in Libreville, Gabon

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Epidemiology of sickle cell disease in Saudi Arabia

“…This distribution reflects the fact that sickle-cell trait confers a survival advantage against malaria and that selection pressure due to malaria has resulted in high frequencies of the mutant gene, especially in the areas of high malarial transmission 12. Although a single abnormal gene may protect against malaria, inheritance of two abnormal genes leads to SCD and confers no such protection, and malaria is one of the major causes of morbidity and death in children with SCD in Africa 1314…”

An investigation of the protective effect of alpha+‐thalassaemia against severe Plasmodium falciparum amongst children in Kumasi, Ghana

“…Sickle cell disease has been described as a double-edged sword with evidence suggesting that those with the sickle cell trait (HbAS) are protected against malaria whilst those with HbSS not only suffer severe health problems but also generally die from malaria (McAuley et al, 2010).…”

“…About 70% of the sickle cell anaemia (SCA) occurs in sub-Saharan Africa where recent reports suggest that 50% to 80% of affected children die annually (Makani et al, 2009 et al, 2010). Sickle cell disease has been described as a double-edged sword with evidence suggesting that those with the sickle cell trait (HbAS) are protected against malaria whilst those with HbSS not only suffer severe health problems but also generally die from malaria (McAuley et al, 2010). HbAS individuals are not only protected against the severe effects of malaria due to an early and enhanced acquisition of protective immunity (Aluoch 1997), they also enjoy significant protection against severe malarial anaemia, and high-density parasitaemia (Aidoo et al, 2002).…”