Two evolutionary models for the interactions of dietary organic cyanogens, hemoglobins, and falciparum malaria

Significant regional and ethnic variations in hemoglobin S frequencies among 485 adult nonpregnant Liberian women uniformly exposed to holoendemic falciparum malaria suggest that an additional major factor may influence the distribution of this hemoglobinopathy and the severity of the infectious disease with which it is causally associated. The differential consumption of organic cyanogen-rich cassava (Manihot esculenta) foodstuffs and subsequent dosage-dependent in vivo exposure to sublethal CN^- , SCN^- , and CNO^- may directly interact with hemoglobin S by inhibiting sickling diathesis, and, at higher intakes, this dietary factor may adversely affect Plasmodium survival and antigenicity. In this study, low dietary organic cyanogen intakes (0.3 mg CN^- /kg body wt/day) in NW and W geographical areas are associated with higher regional hemoglobin S gene frequencies (11%; phenotypic incidence 20%), lower mean (± SD) positive Plasmodium antibody titers (861.6 ± 102.4), and a higher mean (± SEM) prevalence of clinical falciparum malaria [3.04 times (± 0.09) within the previous 12 months]. In contrast, high dietary organic cyanogen intakes (1.5 mg CN^- /kg body wt/day in SE and C geographical areas) are associated with lower hemoglobin S gene frequencies (2%; phenotypic incidence 4%), higher mean (± SD) positive Plasmodium antibody titers (968.7 ± 160.5), and a lower mean (± SEM) prevalence of clinical falciparum malaria [1.73 times (± 0.11) within the previous 12 months]. No other significant malaria-linked genetic variation exists between regions or ethnic groups. Two evolutionary models are hypothesized to suggest how 18 generations of differential dietary organic cyanogen intakes could produce two distinct patterns of change in hemoglobin S gene frequencies, modifying both the cadence and direction of evolution.