Resistance of Anopheles gambiae s.s. against commonly used insecticides and implication of cytochrome P450 monooxygenase in resistance to pyrethroids in Lambaréné (Gabon).
Animals
Anopheles
/ drug effects
Insecticide Resistance
/ genetics
Insecticides
/ pharmacology
Pyrethrins
/ pharmacology
Cytochrome P-450 Enzyme System
/ genetics
Gabon
Mosquito Vectors
/ drug effects
Permethrin
/ pharmacology
Nitriles
/ pharmacology
Larva
/ drug effects
Piperonyl Butoxide
/ pharmacology
Voltage-Gated Sodium Channels
/ genetics
Acetylcholinesterase
/ metabolism
Female
A. gambiae s.s.
Cytochrome p450
Gabon
Pyrethroids
Resistance intensity
Journal
BMC infectious diseases
ISSN: 1471-2334
Titre abrégé: BMC Infect Dis
Pays: England
ID NLM: 100968551
Informations de publication
Date de publication:
30 Oct 2024
30 Oct 2024
Historique:
received:
29
05
2024
accepted:
30
09
2024
medline:
31
10
2024
pubmed:
31
10
2024
entrez:
31
10
2024
Statut:
epublish
Résumé
Insecticides are a crucial component of vector control. However, resistance constitute a threat on their efficacy and the gains obtained over the years through malaria vector control. In Gabon, little data on phenotypic insecticide resistance in Anopheles vectors are published, compromising the rational implementation of resistance management strategies. We assessed the susceptibility to pyrethroids, carbamates and organophosphates of Anopheles gambiae sensu lato (s.l.) and discuss the mechanisms involved in the pyrethroid resistance-phenotype. A. gambiae s.l. larvae were collected from breeding sites in Lambaréné. Emerging adults were used in WHO tube assays at an insecticide concentration that defines resistance (diagnostic concentration). Subsequently, deltamethrin and permethrin were used at 5x and 10x diagnostic concentrations and after preexposure with the cytochrome p450 (and glutathione S-transferase) inhibitor piperonyl butoxide (PBO). A subset of mosquitoes was typed by molecular methods and screened using Taqman assays for mutations conferring target site resistance at the Voltage-gated sodium channel 1014 (Vgsc-1014) locus and the acetylcholinesterase (Ace-1) gene. All mosquitoes were A. gambiae sensu stricto (s.s.) and resistant to permethrin, deltamethrin and alphacypermethrin (mortality less than 98%). However, mosquitoes were susceptible to malathion but resistant to bendiocarb. The level of resistance was high for permethrin and at least moderate for deltamethrin. Pre-exposure to PBO significantly increased the mortality of resistant mosquitoes (P < 0.0001). They became fully susceptible to deltamethrin and permethrin-induced mortality increased 4-fold. The G119S Ace-1 resistance allele, which confers resistance to both organophosphates and carbamates, was not present. All sampled mosquitoes were either homozygous for the Vgsc-L1014F or heterozygous for Vgsc-L1014F/L1014S, a marker for resistance to pyrethroids and organochlorides. These findings demonstrate a role of cytochrome P450 monooxygenases in the pyrethroid-resistance of A. gambiae s.s. from Lambaréné. Combining PBO with pyrethroids, as done in second generation bednets, may be used to revert resistance. In addition, malathion could also be used in combination with pyrethroids-based methods for resistance management.
Sections du résumé
BACKGROUND
BACKGROUND
Insecticides are a crucial component of vector control. However, resistance constitute a threat on their efficacy and the gains obtained over the years through malaria vector control. In Gabon, little data on phenotypic insecticide resistance in Anopheles vectors are published, compromising the rational implementation of resistance management strategies. We assessed the susceptibility to pyrethroids, carbamates and organophosphates of Anopheles gambiae sensu lato (s.l.) and discuss the mechanisms involved in the pyrethroid resistance-phenotype.
METHODS
METHODS
A. gambiae s.l. larvae were collected from breeding sites in Lambaréné. Emerging adults were used in WHO tube assays at an insecticide concentration that defines resistance (diagnostic concentration). Subsequently, deltamethrin and permethrin were used at 5x and 10x diagnostic concentrations and after preexposure with the cytochrome p450 (and glutathione S-transferase) inhibitor piperonyl butoxide (PBO). A subset of mosquitoes was typed by molecular methods and screened using Taqman assays for mutations conferring target site resistance at the Voltage-gated sodium channel 1014 (Vgsc-1014) locus and the acetylcholinesterase (Ace-1) gene.
RESULTS
RESULTS
All mosquitoes were A. gambiae sensu stricto (s.s.) and resistant to permethrin, deltamethrin and alphacypermethrin (mortality less than 98%). However, mosquitoes were susceptible to malathion but resistant to bendiocarb. The level of resistance was high for permethrin and at least moderate for deltamethrin. Pre-exposure to PBO significantly increased the mortality of resistant mosquitoes (P < 0.0001). They became fully susceptible to deltamethrin and permethrin-induced mortality increased 4-fold. The G119S Ace-1 resistance allele, which confers resistance to both organophosphates and carbamates, was not present. All sampled mosquitoes were either homozygous for the Vgsc-L1014F or heterozygous for Vgsc-L1014F/L1014S, a marker for resistance to pyrethroids and organochlorides.
CONCLUSION
CONCLUSIONS
These findings demonstrate a role of cytochrome P450 monooxygenases in the pyrethroid-resistance of A. gambiae s.s. from Lambaréné. Combining PBO with pyrethroids, as done in second generation bednets, may be used to revert resistance. In addition, malathion could also be used in combination with pyrethroids-based methods for resistance management.
Identifiants
pubmed: 39478447
doi: 10.1186/s12879-024-10021-y
pii: 10.1186/s12879-024-10021-y
doi:
Substances chimiques
Insecticides
0
Pyrethrins
0
Cytochrome P-450 Enzyme System
9035-51-2
Permethrin
509F88P9SZ
Nitriles
0
Piperonyl Butoxide
LWK91TU9AH
Voltage-Gated Sodium Channels
0
Acetylcholinesterase
EC 3.1.1.7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1221Subventions
Organisme : KfW Entwicklungsbank
ID : BMZ-Nr 2015.69.227 + BMZ-Nr 2016.68.797
Organisme : Deutsche Forschungsgemeinschaft
ID : BO 2494/3‑1
Informations de copyright
© 2024. The Author(s).
Références
Bhatt S, Weiss DJ, Cameron E, Bisanzio D, Mappin B, Dalrymple U, et al. The effect of malaria control on Plasmodium Falciparum in Africa between 2000 and 2015. Nature. 2015;526:207–11.
doi: 10.1038/nature15535
pubmed: 26375008
pmcid: 4820050
WHO. World malaria report 2023. Geneva: World Health Organization; 2023.
Toé KH, Jones CM, N’Fale S, Ismail HM, Dabiré RK, Ranson H. Increased pyrethroid resistance in malaria vectors and decreased bed net effectiveness, Burkina Faso. Emerg Infect Dis. 2014;20:1691–6.
doi: 10.3201/eid2010.140619
pubmed: 25279965
pmcid: 4193182
Boussougou-sambe ST, Eyisap WE, Canis G, Tasse T, Mandeng SE, Mbakop LR, et al. Insecticide susceptibility status of Anopheles gambiae (s. l.) in South-West Cameroon four years after long-lasting insecticidal net mass distribution. Parasit Vectors. 2018;11:391.
doi: 10.1186/s13071-018-2979-1
pubmed: 29973260
pmcid: 6033221
Gueye OK, Tchouakui M, Dia AK, Faye MB, Ahmed AA, Wondji MJ, et al. Insecticide resistance profiling of Anopheles coluzzii and Anopheles gambiae populations in the southern Senegal: role of target sites and metabolic resistance mechanisms. Genes (Basel). 2020;11 12:1403.
doi: 10.3390/genes11121403
Tchouakui M, Mugenzi LMJ, Menze BD, Khaukha JNT, Tchapga W, Tchoupo M, et al. Pyrethroid resistance aggravation in Ugandan malaria vectors is reducing bednet efficacy. Pathogens. 2021;10: 415.
doi: 10.3390/pathogens10040415
pubmed: 33915866
pmcid: 8065452
Nkemngo FN, Wondji CS, Mugenzi LMJ, Terence E, Niang A, Wondji MJ, et al. Multiple insecticide resistance and plasmodium infection in the principal malaria vectors Anopheles Funestus and Anopheles gambiae in a forested locality close to the Yaoundé airport, Cameroon. Wellcome Open Res. 2020;5:5.
Koumba AA, Zinga-koumba CR, Nguema Mintsa R, Comlan P, Asseko GN, Razack Safiou A, et al. Current sensitivity status of Anopheles gambiae (s. l.) (Culicidae) to DDT and pyrethroids in two agricultural sites of Mouila, Gabon. Int J Mosq Res. 2019;6:12–8.
Boussougou–Sambe ST, Ngossanga B, Doumba-Ndalembouly AG, Boussougou LN, Woldearegai TG, Mougeni F, et al. Anopheles gambiae s.s. resistance to pyrethroids and DDT in semi-urban and rural areas of the Moyen-Ogooué Province, Gabon. Malar J. 2023;22:382.
doi: 10.1186/s12936-023-04820-y
pubmed: 38110952
pmcid: 10729327
IRAC. Prevention and management of insecticide resistance in vectors of public health importance. 2nd ed. 2010. Available online: https://irac-online.org/content/uploads/2009/09/VM-Layout-v2.6_LR.pdf . Accessed 15 Apr 2024.
Santolamazza F, Calzetta M, Etang J, Barrese E, Dia I, Caccone A, et al. Distribution of knock-down resistance mutations in Anopheles gambiae molecular forms in west and west-central Africa. Malar J. 2008;7: 74.
doi: 10.1186/1475-2875-7-74
pubmed: 18445265
pmcid: 2405802
Mourou J-R, Coffinet T, Jarjaval F, Pradines B, Amalvict R, Rogier C, et al. Malaria transmission and insecticide resistance of Anopheles gambiae in Libreville and Port-Gentil, Gabon. Malar J. 2010;9: 321.
doi: 10.1186/1475-2875-9-321
pubmed: 21070655
pmcid: 2995799
Mourou J-R, Coffinet T, Jarjaval F, Cotteaux C, Pradines E, Godefroy L. Malaria transmission in Libreville: results of a one year survey. Malar J. 2012;11: 40.
doi: 10.1186/1475-2875-11-40
pubmed: 22321336
pmcid: 3310827
Koumba AA, Sevidzem SL, Ketoh GK, Faye O, M’batchi B, Mavoungou JF, et al. Identification of the knockdown resistance (kdr) mutations in Anopheles gambiae s.l. in the Mouila area, Southwest Gabon. J Entomol Zool Stud. 2018;6:602–7.
Boussougou-Sambe ST, Woldearegai TG, Doumba-Ndalembouly AG, Ngossanga B, Mba RB, Edoa JR, et al. Assessment of malaria transmission intensity and insecticide resistance mechanisms in three rural areas of the Moyen Ogooué Province of Gabon. Parasit Vectors. 2022;15:217.
doi: 10.1186/s13071-022-05320-9
pubmed: 35725630
pmcid: 9208124
WHO. Test procedures for insecticide resistance monitoring in malaria vector mosquitoes 2nd ed. Geneva: World Health Organization; 2016.
Karaağaç SU. Insecticide resistance. In: Insecticides - Advances in integrated pest management. Edited by Perveen F: InTech; 2012. p. 469–78. Available online: https://www.intechopen.com/chapters/25687 . Accessed 28 Mar 2024.
Fotso-Toguem Y, Tene-Fossog B, Mugenzi LMJ, Wondji MJ, Njiokou F, Ranson H, et al. Genetic Diversity of Cytochrome P450s CYP6M2 and CYP6P4 Associated with Pyrethroid Resistance in the Major Malaria Vectors Anopheles coluzzii and Anopheles gambiae from Yaoundé, Cameroon. Genes (Basel). 2023;14:52.
doi: 10.3390/genes14010052
Matowo J, Weetman D, Pignatelli P, Wright A, Charlwood JD, Kaaya R, et al. Expression of pyrethroid metabolizing P450 enzymes characterizes highly resistant Anopheles vector species targeted by successful deployment of PBO-treated bednets in Tanzania. PLoS ONE. 2022;17:e0249440.
doi: 10.1371/journal.pone.0249440
pubmed: 35073324
pmcid: 8786186
Müller P, Chouaïbou M, Pignatelli P, Etang J, Walker ED, Donnelly MJ, et al. Pyrethroid tolerance is associated with elevated expression of antioxidants and agricultural practice in Anopheles arabiensis sampled from an area of cotton fields in Northern Cameroon. Mol Ecol. 2008;17:1145–55.
doi: 10.1111/j.1365-294X.2007.03617.x
pubmed: 18179425
Main BJ, Everitt A, Cornel AJ, Hormozdiari F, Lanzaro GC. Genetic variation associated with increased insecticide resistance in the malaria mosquito, Anopheles coluzzii. Parasites Vectors. 2018;11:225.
doi: 10.1186/s13071-018-2817-5
pubmed: 29618373
pmcid: 5885317
Riveron JM, Irving H, Ndula M, Barnes KG, Ibrahim SS, Paine MJI, et al. Directionally selected cytochrome P450 alleles are driving the spread of pyrethroid resistance in the major malaria vector Anopheles Funestus. Proc Natl Acad Sci. 2013;110:252–7.
doi: 10.1073/pnas.1216705110
pubmed: 23248325
Kouassi BL, Edi C, Tia E, Konan LY, Akré MA, Koffi AA, et al. Susceptibility of Anopheles gambiae from Côte d’Ivoire to insecticides used on insecticide-treated nets: evaluating the additional entomological impact of piperonyl butoxide and chlorfenapyr. Malar J. 2020;19:454.
doi: 10.1186/s12936-020-03523-y
pubmed: 33298071
pmcid: 7725118
Hien AS, Soma DD, Maiga S, Coulibaly D, Diabaté A, Belemvire A, et al. Evidence supporting deployment of next generation insecticide treated nets in Burkina Faso: bioassays with either chlorfenapyr or piperonyl butoxide increase mortality of pyrethroid-resistant Anopheles gambiae. Malar J. 2021;20:406.
doi: 10.1186/s12936-021-03936-3
pubmed: 34663348
pmcid: 8524873
Fagbohun IK, Oyeniyi TA, Idowu TE, Otubanjo OA, Awolola ST. Cytochrome P450 mono-oxygenase and resistance phenotype in DDT and deltamethrin-resistant Anopheles gambiae (Diptera: Culicidae) and Culex quinquefasciatus in Kosofe, Lagos, Nigeria. J Med Entomol. 2019;56:817–21.
doi: 10.1093/jme/tjz006
pubmed: 30753574
pmcid: 6467639
Sylla EHK, Kun JFJ, Kremsner PG. Mosquito distribution and entomological endemic areas in Gabon inoculation rates in three malaria-endemic areas in Gabon. Trans R Soc Trop Med Hyg. 2000;94:652–6.
doi: 10.1016/S0035-9203(00)90219-0
pubmed: 11198649
Sylla E, Lell B, Kun J, Kremsner P. Plasmodium Falciparum transmission intensity and infection rates in children in Gabon. Parasitol Res. 2001;87:530–3.
doi: 10.1007/s004360100407
pubmed: 11484848
Livak KJ. Organization and mapping of a sequence on the Drosophila melanogaster X and Y chromosomes that is transcribed during spermatogenesis. Genetics. 1984;107:611–34.
doi: 10.1093/genetics/107.4.611
pubmed: 6430749
pmcid: 1202380
Santolamazza F, Mancini E, Simard F, Qi Y, Tu Z, della Torre A. Insertion polymorphisms of SINE200 retrotransposons within speciation islands of Anopheles gambiae molecular forms. Malar J. 2008;7: 163.
doi: 10.1186/1475-2875-7-163
pubmed: 18724871
pmcid: 2546427
Bass C, Nikou D, Donnelly MJ, Williamson MS, Ranson H, Ball A, et al. Detection of knockdown resistance (kdr) mutations in Anopheles gambiae: a comparison of two new high-throughput assays with existing methods. Malar J. 2007;6: 111.
doi: 10.1186/1475-2875-6-111
pubmed: 17697325
pmcid: 1971715
Bass C, Nikou D, Vontas J, Williamson MS, Field LM. Development of high-throughput real-time PCR assays for the identification of insensitive acetylcholinesterase (ace-1R) in Anopheles gambiae. Pestic Biochem Physiol. 2010;96:80–5.
doi: 10.1016/j.pestbp.2009.09.004
Giner M, Vassal C, Kouaik Z, Chiroleu F, Vassal J. Win DL version 2.0. CIRAD (Centre de coopération Internationale en Recherche Agronomique pour le Développement. France: Montpellier: 1999.
Badolo A, Traore A, Jones CM, Sanou A, Flood L, Guelbeogo WM, et al. Three years of insecticide resistance monitoring in Anopheles gambiae in Burkina Faso: resistance on the rise ? Malar J. 2012;11: 232.
doi: 10.1186/1475-2875-11-232
pubmed: 22799568
pmcid: 3489511
Padonou GG, Sezonlin M, Ossé R, Aizoun N, Oké-agbo F, Oussou O, et al. Impact of three years of large scale indoor residual spraying (IRS) and Insecticide Treated Nets (ITNs) interventions on insecticide resistance in Anopheles gambiae s. l. in Benin. Parasit Vectors. 2012;5: 72.
doi: 10.1186/1756-3305-5-72
pubmed: 22490146
pmcid: 3379941
Kumala J, Koekemoer LL, Coetzee M, Mzilahowa T. Intensity of insecticide resistance in the major malaria vector Anopheles Funestus from Chikwawa, rural Southern Malawi. Parasit Vectors. 2022;15:220.
doi: 10.1186/s13071-022-05299-3
pubmed: 35729623
pmcid: 9210055
Sovi A, Keita C, Sinaba Y, Dicko A, Traore I, Cisse MBM, et al. Anopheles gambiae (s.l.) exhibit high intensity pyrethroid resistance throughout Southern and Central Mali (2016–2018): PBO or next generation LLINs may provide greater control. Parasit Vectors. 2020;13:239.
doi: 10.1186/s13071-020-04100-7
pubmed: 32384907
pmcid: 7206711
Ngufor C, Tungu P, Malima R, Kirby M, Kisinza W, Rowland M. Insecticide-treated net wall hangings for malaria vector control: an experimental hut study in north-eastern Tanzania. Malar J. 2014;13: 366.
doi: 10.1186/1475-2875-13-366
pubmed: 25231168
pmcid: 4180361
Ngufor C, Critchley J, Fagbohoun J, Guessan RN. Chlorfenapyr (A Pyrrole Insecticide) applied alone or as a mixture with alpha- cypermethrin for indoor residual spraying against pyrethroid resistant Anopheles gambiae Sl: an experimental hut study in. 2016:1–14.
Ochomo EO, Bayoh NM, Walker ED, Abongo BO, Ombok MO, Ouma C, et al. The efficacy of long-lasting nets with declining physical integrity may be compromised in areas with high levels of pyrethroid resistance. Malar J. 2013;12: 368.
doi: 10.1186/1475-2875-12-368
pubmed: 24156715
pmcid: 4016513
Machani MG, Ochomo E, Zhong D, Zhou G, Wang X, Githeko AK, et al. Phenotypic, genotypic and biochemical changes during pyrethroid resistance selection in Anopheles gambiae mosquitoes. Sci Rep. 2020;10:19063.
Staedke SG, Gonahasa S, Dorsey G, Kamya MR, Maiteki-sebuguzi C, Lynd A, et al. Effect of long-lasting insecticidal nets with and without piperonyl butoxide on malaria indicators in Uganda (LLINEUP): a pragmatic, cluster-randomised trial embedded in a national LLIN distribution campaign. Lancet. 2020;395:1292–303.
doi: 10.1016/S0140-6736(20)30214-2
pubmed: 32305094
pmcid: 7181182
Maiteki-sebuguzi C, Gonahasa S, Kamya MR, Mbchb B, Mutungi Bsc P, Kigozi SP, et al. Effect of long-lasting insecticidal nets with and without piperonyl butoxide on malaria indicators in Uganda (LLINEUP): final results of a cluster-randomised trial embedded in a national distribution campaign. Lancet Infect Dis. 2023;23:247–58.
doi: 10.1016/S1473-3099(22)00469-8
pubmed: 36174592
Burton MJ, Mellor IR, Duce IR, Davies TGE, Field LM, Williamson MS. Differential resistance of insect sodium channels with kdr mutations to deltamethrin, permethrin and DDT. Insect Biochem Mol Biol. 2011;41:723–32.
doi: 10.1016/j.ibmb.2011.05.004
pubmed: 21640822
Ibrahim SS, Fadel AN, Tchouakui M, Terence E, Wondji MJ, Tchoupo M, et al. High insecticide resistance in the major malaria vector Anopheles coluzzii in Chad Republic. Infect Dis Poverty. 2019;8:8.
doi: 10.1186/s40249-019-0605-x
Elanga-Ndille E, Nouage L, Ndo C, Binyang A, Assatse T, Nguiffo-Nguete D, et al. The g119s acetylcholinesterase (Ace-1) target site mutation confers carbamate resistance in the major malaria vector anopheles Gambiae from Cameroon: a challenge for the coming irs implementation. Genes (Basel). 2019;10:1–14.
doi: 10.3390/genes10100790