Hemoglobin variants and disease manifestations in severe falciparum malaria

作者：May Juergen; Evans Jennifer A; Timmann Christian; Ehmen Christa; Busch Wibke; Thye Thorsten; Agbenyega Tsiri; Horstmann Rolf D^*

来源：JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2007, 297(20): 2220-2226.

DOI：10.1001/jama.297.20.2220

Context The geographical distributions of hemoglobin S (HbS), hemoglobin C (HbC), and alpha(+)-thalassemia (-alpha) strongly suggest balancing selection with malaria. However, whereas several studies indicate that the HbS carrier state protects against all major forms of clinical malaria, malaria protection on clinical grounds has been more difficult to confirm for HbC and -alpha, and questions remain as to whether it applies to all forms of the disease.
Objective To assess the association between major clinical forms of severe falciparum malaria and HbS, HbC, and -alpha.
Design, Setting, and Participants Case-control study of 2591 children with severe falciparum malaria enrolled at a tertiary referral center in Ghana, West Africa, and 2048 age-, sex-, and ethnicity-matched control participants recruited by community surveys.
Main Outcome Measures Frequencies of HbS, HbC, and -alpha in patients and controls, including stratifications of patients for signs of disease.
Results Patients presented with partly overlapping signs of disease, including severe anemia (64%), cerebral malaria (22%), respiratory distress (30%), hyperparasitemia (32%), prostration (52%), acidosis (59%), and hyperlactatemia (56%). Carrier states of HbS, HbC, and -alpha were found in 1.4%, 9.4%, and 25.2% of the patients, respectively, and 14.8%, 8.7%, and 27.3% of controls. The HbS carrier state was negatively associated with all forms of the disease studied (overall odds ratio [OR], 0.08; 95% confidence interval [CI], 0.06-0.12). The HbC carrier state showed a negative association selectively with cerebral malaria (OR, 0.64; 95% CI, 0.45-0.91), and the -alpha carrier state showed a negative association selectively with severe anemia (OR, 0.82; 95% CI, 0.69-0.96).
Conclusion Whereas the HbS carrier state was found to be negatively associated with all major forms of severe falciparum malaria, the negative associations of the carrier states of HbC and -alpha appeared to be limited to cerebral malaria and severe anemia, respectively.

• 出版日期2007-5-23
• 单位河北医科大学