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Children with sickle cell disease may not be at higher risk for malaria
The prevalence of Plasmodium falciparum may be lower among children with sickle cell disease than it is among children without sickle cell disease, according to findings from a study conducted in Kenya.
Initial data were collected prospectively from children aged 13 years and younger who were admitted to Kilifi District Hospital. Researchers conducted a retrospective analysis of the data to determine the prevalence, clinical features and outcome of malarial infections among 35,529 children. Results were stratified by sickle cell disease status among the children. The study was conducted from July 1998 to June 2005.
The researchers analyzed 555 hospital admissions among 309 children with sickle cell disease. The prevalence of sickle cell disease in the study population was 1.6%.
The prevalence of P. falciparum was 15.6% among children with sickle cell disease and 41.3% among children who did not have sickle cell disease (P<.001).
The average P. falciparum parasite density among children with sickle cell disease was 2,205 parasites/mcL, compared with 23,878 parasites/mcL among children who did not have the disease (P<.001).
Among parasitemic patients, 16.3% of children with sickle cell disease had features consistent with a diagnosis of severe malaria, compared with 24.7% of children who did not have sickle cell disease (P=.07).
The researchers observed no association between malarial parasitemia and mortality.
Komba AN. Clin Infect Dis. 2009;49:216-222.
This is an interesting study that challenges Haldane’s hypothesis of ‘balanced polymorphism’ as discussed in the accompanying editorial by Professor Geoff Pasvol. In this hypothesis, a particular genetic polymorphism is stably maintained in a population by natural selection, because the survival advantage in heterozygotes for the particular alleles is offset by poorer outcomes in homozygotes. The prevalence of sickle cell trait in Africa is certainly strongly driven by the geographical prevalence of malaria, ranging from <1% in South Africa to 30-40% in parts of central Africa. Patients with sickle trait are protected from malaria and its attendant mortality, but Haldane’s hypothesis and other circumstantial clinical data have previously suggested that the outcome of falciparum malaria is worse in patients with (homozygous) sickle cell disease. This retrospective study — which could be prone to erroneous conclusions for unclear reasons — reaches the exact opposite conclusion, and as such it is likely to provoke future debate.
– Nigel S. Key, MD
Harold R. Roberts Professor of Medicine, Division of
Hematology-Oncology
UNC Chapel Hill