疟原虫分离株对强力霉素的敏感性与 pftetQ 序列多态性以及 pftetQ 和 pfmdt 拷贝数有关。

Susceptibility of Plasmodium falciparum isolates to doxycycline is associated with pftetQ sequence polymorphisms and pftetQ and pfmdt copy numbers.

机构信息

Unité de Recherche en Biologie et Epidémiologie Parasitaires, Institut de Recherche Biomédicale des Armées, Antenne de Marseille, Institut de Médecine Tropicale du Service de Santé des Armées, Allée du médecin colonel Eugène Jamot, France.

出版信息

J Infect Dis. 2010 Jan 1;201(1):153-9. doi: 10.1086/648594.

DOI:10.1086/648594

PMID:19929377

Abstract

BACKGROUND

Doxycycline is used in combination with quinine for malaria treatment or alone for malaria chemoprophylaxis. However, the occurrence of malaria after doxycycline chemoprophylaxis has been reported. Identification of genetic determinants that contribute to the susceptibility of Plasmodium falciparum to doxycycline will be important for the detection and surveillance of doxycycline resistance.

METHODS

Sequence analysis of 11 genes (pftufA, pfEF-TS, pfmdt, pftetQ, pfrps3, pfrps7, pfrps8, pfrps9, pfrps11, pfrps14, and pfrps17) and evaluation of pfmdt and pftetQ copy numbers by quantitative real-time polymerase chain reaction were conducted in 90 African P. falciparum isolates that were obtained from 14 countries and that belonged to phenotypic groups differing in their doxycycline median inhibitory concentrations.

RESULTS

We found that pfmdt copy number of >1 (adjusted odds ratio [OR], 7.09 [95% confidence interval {CI}, 1.58-31.82]; P=.011), pftetQ copy number of >1 (adjusted OR, 5.23 [95% CI, 1.06-25.77]; P=.042), and KYNNNN amino acid motif repeats of <3 (adjusted OR, 3.00 [95% CI, 1.02-8.86]; P=.046) were independently associated with decreased susceptibility to doxycycline.

CONCLUSIONS

Our findings suggest that pfmdt and pftetQ copy numbers and pftetQ sequence polymorphisms are potential molecular markers of decreased in vitro susceptibility to doxycycline in African P. falciparum isolates.

摘要

背景

多西环素与奎宁联合用于治疗疟疾，或单独用于疟疾化学预防。然而，已经有报道称在多西环素化学预防后仍会发生疟疾。鉴定导致恶性疟原虫对多西环素敏感性的遗传决定因素对于检测和监测多西环素耐药性非常重要。

方法

对来自 14 个国家的 90 株非洲恶性疟原虫分离株进行了 11 个基因（pftufA、pfEF-TS、pfmdt、pftetQ、pfrps3、pfrps7、pfrps8、pfrps9、pfrps11、pfrps14 和 pfrps17）的序列分析，并通过实时定量聚合酶链反应评估了 pfmdt 和 pftetQ 拷贝数。这些分离株属于表型组，其多西环素中位数抑制浓度不同。

结果

我们发现 pfmdt 拷贝数>1（调整后的比值比[OR]，7.09[95%置信区间{CI}，1.58-31.82]；P=.011）、pftetQ 拷贝数>1（调整后的 OR，5.23[95%CI，1.06-25.77]；P=.042）和 KYNNNN 氨基酸重复序列<3（调整后的 OR，3.00[95%CI，1.02-8.86]；P=.046）与多西环素敏感性降低独立相关。