It may be possible that the inter-ethnic differences in neutrophil counts may be the consequence of human adaptation to malaria, similar to the thalassemias and hemoglobin S. We base this speculation on three epidemiological observations. First, there is a superimposition of the distribution of
Plasmodium falciparum and the geographic distribution of populations with low neutrophil counts. Second, there is an inverse correlation between the intensity of exposure to
Plasmodium falciparum and the mean neutrophil count in the same population. Historically (before Columbus), Mexicans were never exposed to malaria and have the highest mean neutrophil count (Fig
7) and the lowest prevalence of neutropenia (0.4%) [
2]. In contrast, the Arabs and Africans have a long history of endemic malaria and both have low mean neutrophil count and a high prevalence of neutropenia of 10.7% and 4.4%, respectively [
1,
2]. Similarly, ANCs are lower in Yemeni and Ethiopian Jews, who both reside in regions with malaria and have a high frequency of neutropenia [
9,
10]. Historically, Europeans had a relatively mild exposure to
P. falciparum and their mean neutrophil count and the prevalence of neutropenia (0.8%) are also low. A third observation in support of malaria hypothesis is a direct correlation between the age-specific mortality from malaria and the age-specific prevalence of BN. Mortality from malaria is highest in the first five years of life when the prevalence of neutropenia appears to be highest [
2]. The mechanism by which a low neutrophil count could provide a survival advantage in malarial infections is unclear. Neutrophils are charged with multiple toxic molecules which could direct destructive processes in the brain and lungs which are the most common causes of deaths due
P. falciparum [
20]. Thus, a lower neutrophil and monocyte count found in subjects with BN may be associated with fewer deaths from malaria by causing a less destructive tissue reaction.