刚果共和国布拉柴维尔南部地区居民中耐磺胺多辛-乙胺嘧啶恶性疟原虫的分子标志物概况
Profile of molecular markers of Sulfadoxine-Pyrimethamine-resistant Plasmodium falciparum in individuals living in southern area of Brazzaville, Republic of Congo.
作者信息
Djontu Jean Claude, Baina Marcel Tapsou, Mbama Ntabi Jacque Dollon, Lissom Abel, Umuhoza Dieu Merci, Assioro Doulamo Naura Veil, Vouvoungui Christevy Jeanney, Boumpoutou Reauchelvy Kamal, Mouanga Alain Maxime, Nguimbi Etienne, Ntoumi Francine
机构信息
Fondation Congolaise pour la Recherche Médicale, Brazzaville, Congo; Biotechnology Center, University of Yaounde I, Yaounde, Cameroon.
Fondation Congolaise pour la Recherche Médicale, Brazzaville, Congo; Faculté des Sciences et Techniques, Université Marien Ngouabi, Brazzaville, Congo.
出版信息
Int J Parasitol Drugs Drug Resist. 2024 Dec;26:100569. doi: 10.1016/j.ijpddr.2024.100569. Epub 2024 Oct 26.
BACKGROUND
Although the seasonal and perennial malaria chemopreventions are not implemented in the Republic of Congo, resistance to Sulfadoxine-pyrimethamine (SP) threatens the intermittent preventive treatment during pregnancy (IPTp-SP) and others treatments using the drug. The objective of this study was to determine the prevalence of molecular markers of P.falciparum resistance to SP in individuals with microscopic malaria infection in the south of Brazzaville.
METHODS
Two parallel surveys (health facilities and community-based cross sectional studies) were carried out in urban and rural areas in southern Brazzaville. Between March and October 2021, blood samples were collected from 328 P. falciparum microscopic positive individuals (1-83 years old, and sex ratio female/male of 1.1) to characterize dhfr and dhps genes involved in the P.falciparum resistance to SP. Restriction Fragment Length Polymorphism PCR was used for the detection of mutations within these parasite genes.
RESULTS
High prevalence of mutations was reported within Pfdhfr gene: N51I; 328/328 (100%) ratio (prevalence) [95 CI uncertainty], C59R; 317/328 (96.6 %) [94.1-98.1%], S108N; 326/326 (100%), N164L; 3/326 (0.9%) [0.3-2.7%], and Pfdhps gene: A437G; 292/327 (89.3%) [85.5-92.2%], K540E; 140/327(42.8 %) [37.6-48.2%], A581G; 136/325 (41.8%) [36.6-42.3%]. The quintuple mutant (N51I + C59R + S108N + A437G + K540E) and sextuple mutant haplotypes (N51I + C59R + S108N + A437G + K540E + A581G) were reported for 11/144 (7.6%) [4.3-13.2%] and 5/144 (3.4%) [1.5-7.9%]) of the participants respectively. The K540E and A437G mutants were more prevalent in the rural community; 81/139 (58.3%) [50.0-66.1%] and 135/139 (97.1%) [92.8-98.9%] respectively) than in the urban community; 21/50 (46.3%) [33.7-59.4%] and 47/54(87.0%) [75.6-93.6%] (p = 0.004 and p˂0.0001 respectively) CONCLUSION: These results indicate high prevalence of SP resistance mutations within the dhfr and dhps genes of P. falciparum isolates circulating in study sites, which may limit the efficacy of treatments using SP in these settings.
背景
虽然刚果共和国未实施季节性和常年性疟疾化学预防措施，但对磺胺多辛-乙胺嘧啶（SP）的耐药性威胁到孕期间歇性预防治疗（IPTp-SP）及其他使用该药物的治疗。本研究的目的是确定布拉柴维尔南部镜检确诊的疟疾感染者中恶性疟原虫对SP耐药分子标志物的流行情况。
方法
在布拉柴维尔南部的城乡地区开展了两项平行调查（医疗机构调查和社区横断面研究）。2021年3月至10月期间，从328例镜检确诊为恶性疟原虫阳性的个体（年龄1 - 83岁，女性/男性性别比为1.1）采集血样，以鉴定参与恶性疟原虫对SP耐药的二氢叶酸还原酶（dhfr）和二氢蝶酸合酶（dhps）基因。采用限制性片段长度多态性聚合酶链反应检测这些寄生虫基因内的突变。
结果
报告显示恶性疟原虫二氢叶酸还原酶基因（Pfdhfr）内突变的高流行率：N51I；比例（流行率）为328/328（100%）[95%置信区间不确定度]，C59R；317/328（96.6%）[94.1 - 98.1%]，S108N；326/326（100%），N164L；3/326（0.9%）[0.3 - 2.7%]；以及二氢蝶酸合酶基因（Pfdhps）：A437G；292/327（89.3%）[85.5 - 92.2%]，K540E；140/327（42.8%）[37.6 - 48.2%]，A581G；136/325（41.8%）[36.6 - 42.3%]。分别有11/144（7.6%）[4.3 - 13.2%]和5/144（3.4%）[1.5 - 7.9%]的参与者报告了五元突变体（N51I + C59R + S108N + A437G + K540E）和六元突变单倍型（N51I + C59R + S108N + A437G + K540E + A581G）。K540E和A437G突变体在农村社区更为普遍；分别为81/139（58.3%）[50.0 - 66.1%]和135/139（97.1%）[92.8 - 98.9%]，高于城市社区；分别为21/50（46.3%）[33.7 - 59.4%]和47/54（87.0%）[75.6 - 93.6%]（p值分别为0.004和p˂0.0001）。结论：这些结果表明，在研究地点流行的恶性疟原虫分离株的dhfr和dhps基因内，SP耐药突变的流行率很高，这可能会限制这些环境中使用SP进行治疗的效果。
Zotero 插件