Profile of molecular markers of Sulfadoxine-Pyrimethamine-resistant Plasmodium falciparum in individuals living in southern area of Brazzaville, Republic of Congo

IF 4.1 2区医学 Q1 PARASITOLOGY

International Journal for Parasitology: Drugs and Drug Resistance Pub Date : 2024-10-26 DOI:10.1016/j.ijpddr.2024.100569

Jean Claude Djontu , Marcel Tapsou Baina , Jacque Dollon Mbama Ntabi , Abel Lissom , Dieu Merci Umuhoza , Naura veil Assioro Doulamo , Christevy Jeanney Vouvoungui , Reauchelvy Kamal Boumpoutou , Alain Maxime Mouanga , Etienne Nguimbi , Francine Ntoumi

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Abstract

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.

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刚果共和国布拉柴维尔南部地区耐磺胺-甲氧苄啶恶性疟原虫分子标记的概况。

背景：虽然刚果共和国没有实施季节性和常年性疟疾化学预防措施，但磺胺乙胺嘧啶（SP）的抗药性威胁着孕期间歇性预防治疗（IPTp-SP）和其他使用该药物的治疗方法。本研究旨在确定布拉柴维尔南部微小疟疾感染者中恶性疟原虫对SP耐药性分子标记的流行情况：在布拉柴维尔南部的城市和农村地区开展了两项平行调查（医疗机构和社区横断面研究）。2021 年 3 月至 10 月间，采集了 328 名恶性疟原虫显微镜下阳性患者（1-83 岁，女性/男性性别比为 1.1）的血样，以确定恶性疟原虫抗 SP 基因 dhfr 和 dhps 的特征。利用限制性片段长度多态性聚合酶链式反应（PCR）检测这些寄生虫基因的突变：结果：据报告，Pfdhfr 基因突变的发生率很高：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%], 以及 Pfdhps 基因：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%]。11/144（7.6%）[4.3-13.2%]和5/144（3.4%）[1.5-7.9%]的参与者分别报告了五倍突变型（N51I + C59R + S108N + A437G + K540E）和六倍突变型单倍型（N51I + C59R + S108N + A437G + K540E + A581G）。K540E 和 A437G 突变体在农村社区（分别为 81/139 (58.3%) [50.0-66.1%] 和 135/139 (97.1%) [92.8-98.9%] ）比在城市社区（分别为 21/50 (46.3%) [33.7-59.4%] 和 47/54(87.0%) [75.6-93.6%] ）更普遍（分别为 p = 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 基因中，SP 抗性突变的发生率很高，这可能会限制在这些环境中使用 SP 治疗的疗效。

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来源期刊

International Journal for Parasitology: Drugs and Drug Resistance PARASITOLOGY-PHARMACOLOGY & PHARMACY

CiteScore

7.90

自引率

7.50%

发文量

审稿时长

48 days

期刊介绍： The International Journal for Parasitology – Drugs and Drug Resistance is one of a series of specialist, open access journals launched by the International Journal for Parasitology. It publishes the results of original research in the area of anti-parasite drug identification, development and evaluation, and parasite drug resistance. The journal also covers research into natural products as anti-parasitic agents, and bioactive parasite products. Studies can be aimed at unicellular or multicellular parasites of human or veterinary importance.