Investigating molecular mechanisms of insecticide resistance in the Eastern Democratic Republic of the Congo

Malaria Journal

Charles McLoughlin¹  Louisa A. Messenger¹  Thomas Walker¹  Vital Byabushi²  Bertin Zawadi³  Janvier Bandibabone³  Chimanuka Bantuzeko⁴  Maite Guardiola⁵  Jorian Prudhomme⁶  Sévérin N’Do⁷  Abdoulaye Diabaté⁸  Muhigwa Jeanberckmans⁹ 

[1] Department of Disease Control, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK;Kibali Gold Mine, Haut-Uele, Democratic Republic of the Congo;Laboratoire d’Entomologie Médicale et Parasitologie, Centre de Recherche en Sciences Naturelles (CRSN/Lwiro), Sud-Kivu, Democratic Republic of the Congo;Laboratoire d’Entomologie Médicale et Parasitologie, Centre de Recherche en Sciences Naturelles (CRSN/Lwiro), Sud-Kivu, Democratic Republic of the Congo;Université Officielle de Bukavu, Bukavu, Democratic Republic of the Congo;Médecins Sans Frontières (MSF) OCBA, Barcelona, Spain;Médecins Sans Frontières (MSF) OCBA, Barcelona, Spain;UMR MIVEGEC (IRD-CNRS – Université de Montpellier), 911 Avenue Agropolis, 34394, Montpellier, France;Médecins Sans Frontières (MSF) OCBA, Barcelona, Spain;Université Nazi Boni (UNB), Bobo-Dioulasso, Burkina Faso;Institut de Recherche en Sciences de la Santé (IRSS)/Centre MURAZ, Bobo-Dioulasso, Burkina Faso;Université Nazi Boni (UNB), Bobo-Dioulasso, Burkina Faso;Université Officielle de Bukavu, Bukavu, Democratic Republic of the Congo;

关键词: Anopheles gambiae;    Anopheles funestus;    Insecticide resistance;    Plasmodium falciparum;    Democratic Republic of the Congo;    Target site mutation;    Metabolic resistance;    Insecticide resistance surveillance;   

DOI  :  10.1186/s12936-021-04002-8

来源: Springer

【 摘 要 】

BackgroundMalaria vector control in the Democratic Republic of the Congo is plagued by several major challenges, including inadequate infrastructure, lack of access to health care systems and preventative measures, and more recently the widespread emergence of insecticide resistance among Anopheles mosquitoes. Across 26 provinces, insecticide resistance has been reported from multiple sentinel sites. However, to date, investigation of molecular resistance mechanisms among Anopheles vector populations in DRC has been more limited.MethodsAdult Anopheles gambiae sensu lato (s.l.) and Anopheles funestus s.l. were collected from two sites in Sud-Kivu province and one site in Haut-Uélé province and PCR-screened for the presence of 11 resistance mutations, to provide additional information on frequency of resistance mechanisms in the eastern DRC, and to critically evaluate the utility of these markers for prospective country-wide resistance monitoring.ResultsL1014F-kdr and L1014S-kdr were present in 75.9% and 56.7% of An. gambiae s.l. screened, respectively, with some individuals harbouring both resistant alleles. Across the three study sites, L43F-CYP4J5 allele frequency ranged from 0.42 to 0.52, with evidence for ongoing selection. G119S-ace1 was also identified in all sites but at lower levels. A triple mutant haplotype (comprising the point mutation CYP6P4-I236M, the insertion of a partial Zanzibar-like transposable element and duplication of CYP6AA1) was present at high frequencies. In An. funestus s.l. cis-regulatory polymorphisms in CYP6P9a and CYP6P9b were detected, with allele frequencies ranging from 0.82 to 0.98 and 0.65 to 0.83, respectively.ConclusionsThis study screened the most up-to-date panel of DNA-based resistance markers in An. gambiae s.l. and An. funestus s.l. from the eastern DRC, where resistance data is lacking. Several new candidate markers (CYP4J5, G119S-ace1, the triple mutant, CYP6P9a and CYP6P9b) were identified, which are diagnostic of resistance to major insecticide classes, and warrant future, larger-scale monitoring in the DRC to inform vector control decisions by the National Malaria Control Programme.

【 授权许可】

CC BY