Plasmodium falciparum malaria and anaemia in childhood

Childhood anaemia represents a major health problem in sub-Saharan Africa. The anaemia is multifactorial and the result of a synergism between infectious diseases, nutritional deficiencies and inherited red cell disorders. In malaria holoendemic areas, small children are continuously parasitaemic but the causal relationship and exact influence of Plasmodium falciparum infection on haemoglobin (Hb) concentration remains largely unsettled.

The association between parasitaemia and Hb was therefore prospectively studied in 211 children during five months. High mean asymptomatic parasite density and presence of clinical malaria episode were major predictors of anaemia in children <24 months. Thus, at study end, Hb represented a function of the area under parasitaemia curve (AUPC) during previous five months, adjusting for age. Clinical malaria episodes were routinely treated with chloroquine. A high early failure rate (20%), especially in the youngest children, however, resulted in immediate and pronounced fall in Hb in the presence of high parasitaemia. Moreover, Hb did not even improve after clinically successful treatment due to deficient clearance of asymptomatic parasitaemia and cumulated Hb loss during repeated malaria episodes. Restored Hb was only achieved after second-line treatment with sulfadoxine-pyrimethamine (SP), but this was only temporary and not sufficient to improve longterm Hb. Hence, prompt malaria case management did not improve parasitaemia and Hb at study end. In an intervention study, regular supplementation with micronutrients and iron for five months improved long-term Hb concentration. A synergistic effect on Hb was obtained in children who received both supplement and SP treatment.

An indepth study was performed on the Hb dynamics in acute P. falciparum malaria. A wide range of Hb falls was found, partly correlated to parasite densities. Balance studies between total Hb, plasma Hb and appearance of Hb in the urine indicated that extravascular erythrocyte clearance was the predominant mode of haemolysis. Fall in Hb was limited in the absence of haemoglobinuria. Increased removal markers on red cells known to induce erythrophagocytosis, i.e. complement C3c fragment and autologous IgG specific for aggregated band 3, correlated to the haemolysis. A similar mechanism for predominantly extravascular erythrocyte clearance may therefore be operative in acute malarial anaemia, normal erythrocyte senescence and other forms of acute haemolysis.

In conclusion, stepwise deterioration in median Hb was found by asymptomatic parasitaemia, clinical malaria episode and, most significantly, treatment failure. To control childhood anaemia, substituting nutritional deficiencies and temporarily clearing parasitaemia was more successful when combined than the sum of either activity alone.

List of scientific papers

I. Ekvall H, Arese P,Turrini F, Ayi K, Mannu F,Premji Z, Björkman A. (2000). Acute haemolysis in childhood falciparum malaria. [Submitted]

II. Ekvall H, Premji Z, Björkman A. (1998). Chloroquine treatment for uncomplicated childhood malaria in an area with drug resistance: early treatment failure aggravates anaemia. Trans R Soc Trop Med Hyg. 92(5):556-560.
https://pubmed.ncbi.nlm.nih.gov/9861379

III. Ekvall H, Premji Z, Bennett S, Björkman A. (2000). Hemoglobin concentration in children in a malaria holoendemic area is determined by cumulated Plasmodium falciparum parasite densities. Am J Trop Med Hyg. [Accepted]
https://pubmed.ncbi.nlm.nih.gov/11425164

IV. Ekvall H, Premji Z, Björkman A. (2000). Micronutrient and iron supplementation and effective antimalarial treatment synergistically improve childhood anaemia. Trop Med Int Health. [Accepted]
https://pubmed.ncbi.nlm.nih.gov/11044264