重症恶性疟中的血红蛋白变异体与疾病表现

Hemoglobin variants and disease manifestations in severe falciparum malaria.

作者信息

May Jürgen, Evans Jennifer A, Timmann Christian, Ehmen Christa, Busch Wibke, Thye Thorsten, Agbenyega Tsiri, Horstmann Rolf D

机构信息

Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.

出版信息

JAMA. 2007 May 23;297(20):2220-6. doi: 10.1001/jama.297.20.2220.

DOI:10.1001/jama.297.20.2220

PMID:17519411

Abstract

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.

摘要

背景

血红蛋白S（HbS）、血红蛋白C（HbC）和α+地中海贫血（-α）的地理分布强烈表明与疟疾存在平衡选择。然而，尽管多项研究表明HbS携带者状态可预防所有主要形式的临床疟疾，但基于临床依据对HbC和-α的疟疾保护作用进行确认则更为困难，对于其是否适用于所有形式的疾病仍存在疑问。

目的

评估严重恶性疟原虫疟疾的主要临床形式与HbS、HbC和-α之间的关联。

设计、地点和参与者：对西非加纳一家三级转诊中心收治的2591例严重恶性疟原虫疟疾儿童以及通过社区调查招募的2048例年龄、性别和种族匹配的对照参与者进行病例对照研究。

主要观察指标

患者和对照中HbS、HbC和-α的频率，包括对患者疾病体征的分层。

结果

患者表现出部分重叠的疾病体征，包括严重贫血（64%）、脑型疟疾（22%）、呼吸窘迫（30%）、高疟原虫血症（32%）、极度虚弱（52%）、酸中毒（59%）和高乳酸血症（56%）。患者中HbS、HbC和-α的携带者状态分别为1.4%、9.4%和25.2%，对照中分别为14.8%、8.7%和27.3%。HbS携带者状态与所研究的所有疾病形式均呈负相关（总体优势比[OR]，0.08；95%置信区间[CI]，0.06 - 0.12）。HbC携带者状态仅与脑型疟疾呈负相关（OR，0.64；95%CI，0.45 - 0.91），而-α携带者状态仅与严重贫血呈负相关（OR，0.82；95%CI，0.69 - 0.96）。