2023年莫桑比克恶性疟原虫富含组氨酸蛋白2/3基因缺失的分子监测

Molecular surveillance of Plasmodium falciparum histidine-rich protein 2/3 gene deletions in Mozambique, 2023.

作者信息

da Silva Clemente, Tembisse Dário, Cisteró Pau, Rovira-Vallbona Eduard, Canana Neide, da Costa Paulino, Matambisso Gloria, Aranda-Díaz Andrés, Mbeve Henriques, Ndimande Nelo, Timana Alcido, Hunguana Aura, Boene Simone, Pujol Arnau, Rafael Bernardete, Greenhouse Bryan, Enosse Sónia, Saúte Francisco, Candrinho Baltazar, Mayor Alfredo

机构信息

Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique.

ISGlobal, Barcelona, Spain.

出版信息

Malar J. 2024 Dec 26;23(1):402. doi: 10.1186/s12936-024-05230-4.

DOI:10.1186/s12936-024-05230-4

PMID:39725959

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11674202/

Abstract

BACKGROUND

Rapid diagnostic tests (RDTs) based on the detection of Plasmodium falciparum histidine rich protein 2 (PfHRP2) are widely used for the diagnostic of P. falciparum in Africa. However, deletions of the pfhrp2 and pfhrp3 genes can lead to false negative test results and compromise appropriate case management. Due to the high burden of malaria in Mozambique, it is crucial to monitor the potential emergence of parasites with pfhrp2/3 gene deletions in the country.

METHODS

The presence of pfhrp2/3 deletions was assessed during the 2023 high transmission season in 34 health facilities from 9 districts across 6 provinces in Mozambique. Children between 2 and 10 years of age attending the health facility with fever were tested by both the routine HRP2-RDT and a P. falciparum lactate dehydrogenase (PfLDH)-RDT, and dried blood spots (DBS) were collected from those testing positive by one or both RDTs. DBS from children with a negative HRP2-RDT but positive PfLDH-RDT were tested for the presence of pfhrp2/3 deletions by multiplex real time quantitative polymerase chain reaction (qPCR).

RESULTS

3208 children attended the health facilities during the study. 81.6% (2612/3208) participants were positive for at least one malaria RDT and, among them, 0.8% (210/2612) had discrepant RDT results (22 HRP2 - but LDH + and 188 HRP2 + but LDH -). The overall prevalence of suspected false-negative HRP2-RDT results in Mozambique was 0.91% (95% CI 0.58-1.39; 22/2424). pfhrp2/3 gene deletions were confirmed in 4 cases (1 in Nampula and 3 in Inhambane). Therefore, the prevalence of P. falciparum confirmed cases with pfhrp2/3 gene deletions in the six provinces sampled was 0.16% (95% CI 0.15-2.57; 4/2424), being 0.27% (95% CI 0.01-1.75; 1/367) in Nampula and 0.59% (95% CI 0.15-1.88; 3/503) in Inhambane.

CONCLUSION

pfhrp2/3 gene deletions were detected in 2 out of 6 provinces surveyed in Mozambique, but at a prevalence far below the 5% threshold recommended for a change in HRP2-based-RDT.

摘要

背景

基于检测恶性疟原虫富含组氨酸蛋白2（PfHRP2）的快速诊断检测（RDT）在非洲被广泛用于诊断恶性疟原虫。然而，pfhrp2和pfhrp3基因的缺失可导致检测结果出现假阴性，并影响适当的病例管理。由于莫桑比克疟疾负担沉重，监测该国出现pfhrp2/3基因缺失寄生虫的可能性至关重要。

方法

在2023年高传播季节，对莫桑比克6个省份9个地区的34个医疗机构进行了pfhrp2/3基因缺失情况评估。到医疗机构就诊的2至10岁发热儿童同时接受常规HRP2-RDT和恶性疟原虫乳酸脱氢酶（PfLDH）-RDT检测，并从通过一种或两种RDT检测呈阳性的儿童中采集干血斑（DBS）。对HRP2-RDT检测为阴性但PfLDH-RDT检测为阳性的儿童的DBS进行多重实时定量聚合酶链反应（qPCR）检测，以确定是否存在pfhrp2/3基因缺失。

结果

在研究期间，有3208名儿童到医疗机构就诊。81.6%（2612/3208）的参与者至少一项疟疾RDT检测呈阳性，其中0.8%（210/2612）的RDT结果不一致（22例HRP2阴性但LDH阳性，188例HRP2阳性但LDH阴性）。在莫桑比克，疑似HRP2-RDT假阴性结果的总体患病率为0.91%（95%CI 0.58-1.39；22/2424）。共确诊4例pfhrp2/3基因缺失（楠普拉省1例，伊尼扬巴内省3例）。因此，在抽样的6个省份中，确诊病例中存在pfhrp2/3基因缺失的恶性疟原虫患病率为0.16%（95%CI 0.15-2.57；4/2424），楠普拉省为0.27%（95%CI 0.01-1.75；1/367），伊尼扬巴内省为0.59%（95%CI

0.15-1.88；3/503）。