Malaria and HIV-1 are coendemic in many developing countries, with
anemia being the most common pediatric hematological manifestation of each disease.
Anemia is also one of the primary causes of mortality in children monoinfected with either
malaria or HIV-1. Although our previous results showed HIV-1(+) children with acute
Plasmodium falciparum malaria [Pf(+)] have more profound
anemia, potential causes of severe
anemia in coinfected children remain unknown. As such, children with P.
falciparum malaria (aged 3-36 months, n = 542) from a holoendemic
malaria transmission area of western Kenya were stratified into three groups: HIV-1 negative [HIV-1(-)/Pf(+)]; HIV-1 exposed [HIV-1(exp)/Pf(+)]; and HIV-1 infected [HIV-1(+)/Pf(+)]. Comprehensive clinical, parasitological, and hematological measures were determined upon enrollment. Univariate, correlational, and hierarchical regression analyses were used to determine differences among the groups and to define predictors of worsening
anemia. HIV-1(+)/Pf(+) children had significantly more malarial pigment-containing neutrophils (
PCN), monocytosis, increased severe
anemia (Hb < 6.0 g/dL), and nearly 10-fold greater mortality within 3 months of enrollment. Common causes of
anemia in
malaria-infected children, such as increased
parasitemia or reduced erythropoiesis, did not account for worsening
anemia in the HIV-1(+)/Pf(+) group nor did carriage of
sickle cell trait or
G6PD deficiency. Hierarchical multiple regression analysis revealed that more profound
anemia was associated with elevated PCM, younger age, and increasing HIV-1 status ([HIV-1(-) --> HIV-1(exp) --> HIV-1(+)]. Thus,
malaria/HIV-1
coinfection is characterized by more profound
anemia and increased mortality, with acquisition of monocytic pigment having the most detrimental impact on Hb levels.