Researchers measured plasma concentrations of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) in patients with sickle cell disease (SCD) and malaria to determine their total body load of P falciparum parasites and published their results in The Lancet Child & Adolescent Health.

Uyoga et al conducted a post hoc secondary analysis of data from the Transfusion and Treatment of severe anemia in African Children Trial and assessed the burden of P falciparum parasites in children with SCD through the measurement of plasma PfHRP2 concentrations.

The trial was conducted on 3483 children in 3 different hospitals in Uganda. PfHRP2 was detected in whole blood using the Paracheck rapid diagnostic test (Orchid Biomedical Systems, Goa, India). P falciparum parasite burden, features of severe malaria, and mortality at day 28 in malaria-positive children were the outcomes considered in this secondary analysis.

Among all children who presented with all-cause severe anemia, high plasma concentrations of PfHRP2 were only seen in a small proportion of children with SCD, and median parasite densities were more than 3 times lower in children with SCD than in those without SCD.

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This study is hence consistent with previous studies noting that children with SCD are innately protected from high-density malaria infections. However, even low-density P falciparum infections can have catastrophic effects on hemoglobin concentrations, leading to increased mortality rates.

From their observations, the authors suspect that protection in children with SCD might be conferred due to the reduced ability of P falciparum-infected SCD red blood cells to sequester in the microvasculature. Additionally, all children with SCD who present with signs of severe malaria are infected by parasites of a specific genetic background that may be less virulent. Further work is required to pinpoint which of these mechanisms is most important in vivo.


Uyoga S, Olupot-Olupot P, Connon R, et al. Sickle cell anaemia and severe Plasmodium falciparum malaria: a secondary analysis of the Transfusion and Treatment of African Children Trial (TRACT)Lancet Child Adolesc Health. Published online July 1, 2022. doi:10.1016/S2352-4642(22)00153-5