In areas of intense P. falciparum exposure, such as western Kenya, the most lethal complication of malaria is severe malarial anemia (SMA). The pathogenesis of SMA is multi-factorial and not fully understood. Our ongoing studies are, therefore, investigating the hematological manifestations of MA in a cohort of children presenting at a rural district hospital in western Kenya. A total of 619 children aged 3–33 mos. were categorized into 5 groups: SMA (Hb<6.0g/dL); moderate MA (MdMA; 6.0≤Hb<8.0g/dL); mild MA (MlMA; 8.0≤Hb<11.0g/dL); uncomplicated malaria (UM, Hb≥11.0g/dL), and healthy aparasitemic controls (HC). Parasite density, CBC, and reticulocyte count was obtained on all subjects (see table).

HC (n=62)UM (n=36)MlMA (n=139)MdMA (n=161)SMA (n=221)P valuea
Data are presented as mean±SEM. aDifferences between the groups were compared using the Kruskal-Wallis test. *Denotes p<0.05 (Mann-Whitney U test) relative to the HC group. 
Parasitemia (/μL) 82471±15925 51711±5300 51513±5798) 62934±6416 0.107 
Hb (g/dL) 1.81±0.11 11.66±0.14 9.27±0.07* 6.86±0.05* 4.78±0.06* <0.001 
MCV (fL) 71.87±0.71 73.42±1.12 68.57±0.63* 69.25±0.76* 71.34±0.67 0.001 
Reticulocyte count (%) 1.57±0.20 1.64±0.24 2.55±0.16* 4.21±0.29* 5.50±0.31* <0.001 
RPI 1.83±0.33 1.90±0.49 1.44±0.09 1.50±0.10 1.15±0.07* 0.001 
HC (n=62)UM (n=36)MlMA (n=139)MdMA (n=161)SMA (n=221)P valuea
Data are presented as mean±SEM. aDifferences between the groups were compared using the Kruskal-Wallis test. *Denotes p<0.05 (Mann-Whitney U test) relative to the HC group. 
Parasitemia (/μL) 82471±15925 51711±5300 51513±5798) 62934±6416 0.107 
Hb (g/dL) 1.81±0.11 11.66±0.14 9.27±0.07* 6.86±0.05* 4.78±0.06* <0.001 
MCV (fL) 71.87±0.71 73.42±1.12 68.57±0.63* 69.25±0.76* 71.34±0.67 0.001 
Reticulocyte count (%) 1.57±0.20 1.64±0.24 2.55±0.16* 4.21±0.29* 5.50±0.31* <0.001 
RPI 1.83±0.33 1.90±0.49 1.44±0.09 1.50±0.10 1.15±0.07* 0.001 

Peripheral blood smears (n=150) were randomly selected from all groups for examination of RBC and WBC morphology, and identification of any clinically significant abnormalities, such as presence of hemozoin (Hz). The majority of the children with malaria had inadequate bone marrow responses (77.6%), as determined by the reticulocyte production index (RPI). Relative to the UM group, the SMA group had increased microcytosis (p<0.005). Moreover, numbers of nucleated RBC (nRBC) and Hz-laden monocytes correlated with increasing degrees of anemia (p=0.08 and p<0.005, respectively). In contrast, levels of parasitemia, prevalence of high-density parasitemia (≥10,000 parasites/ml) and reactive lymphocytes did not differ among the four malaria groups. No significant increases were observed in the number of schistocytes, acanthocytes or spherocytes in any of the groups. Macrocytosis was rarely observed and sickle cells were not detected. These findings illustrate that parasitemia is not associated with the severity of anemia in this population. Conversely, the number of Hz-containing monocytes was a strong predictor of anemia severity, suggesting that SMA results from more chronic malaria infections. Finally, although nRBC were most commonly associated with SMA, the RPI was not appropriately increased for the degree of anemia, illustrating that these children have suppressed and/or ineffective erythropoiesis.

Disclosure: No relevant conflicts of interest to declare.

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