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布基纳法索有或无疟疾儿童季节性疟疾化学预防药物水平和耐药标志物:病例对照研究。

Seasonal Malaria Chemoprevention Drug Levels and Drug Resistance Markers in Children With or Without Malaria in Burkina Faso: A Case-Control Study.

机构信息

Institute for Global Health Sciences, Malaria Elimination Initiative, University of California, San Francisco.

Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso.

出版信息

J Infect Dis. 2023 Oct 3;228(7):926-935. doi: 10.1093/infdis/jiad172.

Abstract

BACKGROUND

Despite scale-up of seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine and amodiaquine (SP-AQ) in children 3-59 months of age in Burkina Faso, malaria incidence remains high, raising concerns regarding SMC effectiveness and selection of drug resistance. Using a case-control design, we determined associations between SMC drug levels, drug resistance markers, and presentation with malaria.

METHODS

We enrolled 310 children presenting at health facilities in Bobo-Dioulasso. Cases were SMC-eligible children 6-59 months of age diagnosed with malaria. Two controls were enrolled per case: SMC-eligible children without malaria; and older (5-10 years old), SMC-ineligible children with malaria. We measured SP-AQ drug levels among SMC-eligible children and SP-AQ resistance markers among parasitemic children. Conditional logistic regression was used to compute odds ratios (ORs) comparing drug levels between cases and controls.

RESULTS

Compared to SMC-eligible controls, children with malaria were less likely to have any detectable SP or AQ (OR, 0.33 [95% confidence interval, .16-.67]; P = .002) and have lower drug levels (P < .05). Prevalences of mutations mediating high-level SP resistance were rare (0%-1%) and similar between cases and SMC-ineligible controls (P > .05).

CONCLUSIONS

Incident malaria among SMC-eligible children was likely due to suboptimal levels of SP-AQ, resulting from missed cycles rather than increased antimalarial resistance to SP-AQ.

摘要

背景

尽管在布基纳法索为 3-59 月龄儿童扩大季节性疟疾化学预防(SMC)范围,使用磺胺多辛-乙胺嘧啶和阿莫地喹(SP-AQ),但疟疾发病率仍然很高,这引发了对 SMC 有效性和抗药性选择的关注。本研究采用病例对照设计,确定 SMC 药物水平、耐药性标志物与疟疾发病之间的关联。

方法

我们在博博迪乌拉索的医疗机构招募了 310 名就诊儿童。病例为符合 SMC 条件、6-59 月龄、诊断为疟疾的儿童。每例病例纳入 2 名对照:符合 SMC 条件、无疟疾的儿童;年龄较大(5-10 岁)、不符合 SMC 条件、患有疟疾的儿童。我们测量了符合 SMC 条件的儿童中的 SP-AQ 药物水平和寄生虫血症儿童中的 SP-AQ 耐药性标志物。采用条件逻辑回归计算病例和对照之间药物水平的比值比(OR)。

结果

与符合 SMC 条件的对照相比,患有疟疾的儿童更不可能检测到任何 SP 或 AQ(OR,0.33 [95%置信区间,0.16-0.67];P=0.002),且药物水平较低(P<0.05)。介导高水平 SP 耐药性的突变的流行率较低(0%-1%),且在病例与不符合 SMC 条件的对照之间相似(P>0.05)。

结论

符合 SMC 条件的儿童中出现的疟疾可能是由于 SP-AQ 水平不理想,这是由于错过了周期,而不是对 SP-AQ 产生了更高的抗药性。

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