坦桑尼亚东北部间歇性预防治疗（IPTsc）对儿童疟疾后抗疟药物耐药性标志物选择缺失。

Lack of selection of antimalarial drug resistance markers after intermittent preventive treatment of schoolchildren (IPTsc) against malaria in northeastern Tanzania.

机构信息

Centre for translational Medicine and Parasitology, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark.

National Institute for Medical Research, Tanga Centre, Tanga, Tanzania; Global Health Institute, University of Antwerp, Antwerp, Belgium.

出版信息

Int J Infect Dis. 2024 Sep;146:107102. doi: 10.1016/j.ijid.2024.107102. Epub 2024 Jun 13.

DOI:10.1016/j.ijid.2024.107102

PMID:38876161

Abstract

OBJECTIVE

Intermittent Preventive Treatment of schoolchildren (IPTsc) is recommended by WHO as a strategy to protect against malaria; to explore whether IPTsc with dihydroartemisinin-piperaquine (DP) or artesunate-amodiaquine (ASAQ) cause a selection of molecular markers in Plasmodium falciparum genes associated with resistance in children in seven schools in Tanga region, Tanzania.

METHODS

SNPs in P. falciparum genes Pfmdr1, Pfexo, Pfkelch13, and Pfcrt and copy number variations in Pfplasmepsin-2 and Pfmdr1 were assessed in samples collected at 12 months (visit 4, n=74) and 20 months (visit 6, n=364) after initiation of IPTsc and compared with the baseline prevalence (n=379).

RESULTS

The prevalence of Pfmdr1 N86 and Pfexo 415G was >99% and 0%, respectively without any temporal differences observed. The prevalence of Pfmdr1 184F changed significantly from baseline (52.2%) to visit 6 (64.6%) (χ=6.11, P=0.013), but no differences were observed between the treatment arms (χ=0.05, P=0.98). Finally, only minor differences in the amplification of Pfmdr1 were observed; from 10.2% at baseline to 16.7% at visit 6 (χ=0.98, P=0.32).

CONCLUSIONS

The IPTsc strategy does not seem to pose a risk for the selection of markers associated with DP or ASAQ resistance. Continuously and timely surveillance of markers of antimalarial drug resistance is recommended.

摘要

目的

世界卫生组织（WHO）建议采用儿童间歇性预防治疗（IPTsc）作为预防疟疾的策略；本研究旨在探索在坦桑尼亚坦噶地区的 7 所学校中，使用双氢青蒿素-哌喹（DP）或青蒿琥酯-阿莫地喹（ASAQ）进行 IPTsc 是否会导致与儿童中抗疟药物耐药相关的 Pfmdr1、Pfexo、Pfkelch13 和 Pfcrt 基因中的分子标记发生选择。

方法

在开始 IPTsc 后 12 个月（第 4 次就诊，n=74）和 20 个月（第 6 次就诊，n=364）采集样本，评估 Pfmdr1、Pfexo、Pfkelch13 和 Pfcrt 基因中的 SNPs，以及 Pfplasmepsin-2 和 Pfmdr1 中的拷贝数变异，并与基线患病率（n=379）进行比较。

结果

Pfmdr1 N86 和 Pfexo 415G 的患病率分别>99%和 0%，且均未观察到时间差异。Pfmdr1 184F 的患病率从基线（52.2%）显著变化至第 6 次就诊（64.6%）（χ=6.11，P=0.013），但在两种治疗组之间无差异（χ=0.05，P=0.98）。最后，Pfmdr1 的扩增仅观察到微小差异；从基线的 10.2%增加到第 6 次就诊时的 16.7%（χ=0.98，P=0.32）。