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