Reply

To the Editor

Kurtzhals et al. [1] call attention to the importance of conducting investigations in different disease-endemic areas by standardized protocols. They rightly point out that there is no hard evidence to show that endemicity-dependent immunologic disparities contribute to differences seen in the clinical presentation of severe malaria in areas with various transmission pressures. This issue clearly deserves further investigation.

With reference to their comment on the tumor necrosis factor (TNF)—α and interleukin (IL)—10 levels in our study groups, we would like to clarify that, at the level of the individual patient, anemic patients had higher levels of TNF than of IL-10, while patients with mild disease had higher IL-10 than TNF [2]. Therefore, the IL-10/TNF ratio was calculated for each patient separately and not by using mean cytokine values. With reference to the differences between the moderately anemic and severely anemic patients, we point out in our paper that there were no statistically significant differences in the IL-10/TNF ratio between the moderately anemic and severely anemic patients. In subjects with severe anemia, there was a trend toward lower levels of both IL-10 and TNF compared with those in moderately anemic patients, but this difference was not statistically significant. Although one can speculate that some of the differences between our study [2] and that of Kurtzhal et al. [3] may be due to endemicity-based immunologic differences, other factors, including differences in study design, intensity of parasite exposure, and genetic background of the study population, must be considered.

In summary, despite differences in methodologies, transmission pressures, and study populations, both studies arrived at similar conclusions. Future studies with comparable case definitions, study design, and standardized protocols applied in different disease-endemic settings will undoubtedly lead to unraveling the pathogenic basis of cerebral malaria and severe malarial anemia.