Distribution of insecticide resistance and mechanisms involved in the arbovirus vector Aedes aegypti in Laos and implication for vector control.
Aedes
/ drug effects
Animals
Biological Assay
Drug Synergism
Female
Gene Dosage
Genes, Insect
Hydrocarbons, Chlorinated
/ pharmacology
Insecticide Resistance
Insecticides
/ pharmacology
Laos
Larva
/ drug effects
Metabolic Networks and Pathways
/ genetics
Mosquito Control
/ methods
Mosquito Vectors
/ drug effects
Mutation
Organophosphates
/ pharmacology
Pyrethrins
/ pharmacology
Journal
PLoS neglected tropical diseases
ISSN: 1935-2735
Titre abrégé: PLoS Negl Trop Dis
Pays: United States
ID NLM: 101291488
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
31
05
2019
accepted:
16
10
2019
revised:
26
12
2019
pubmed:
13
12
2019
medline:
26
2
2020
entrez:
13
12
2019
Statut:
epublish
Résumé
The yellow fever mosquito Aedes aegypti is the major vector of dengue, yellow fever, Zika, and Chikungunya viruses. Worldwide vector control is largely based on insecticide treatments but, unfortunately, vector control programs are facing operational challenges due to mosquitoes becoming resistant to commonly used insecticides. In Southeast Asia, resistance of Ae. aegypti to chemical insecticides has been documented in several countries but no data regarding insecticide resistance has been reported in Laos. To fill this gap, we assessed the insecticide resistance of 11 Ae. aegypti populations to larvicides and adulticides used in public health operations in the country. We also investigated the underlying molecular mechanisms associated with resistance, including target site mutations and detoxification enzymes putatively involved in metabolic resistance. Bioassays on adults and larvae collected in five provinces revealed various levels of resistance to organophosphates (malathion and temephos), organochlorine (DDT) and pyrethroids (permethrin and deltamethrin). Synergist bioassays showed a significant increased susceptibility of mosquitoes to insecticides after exposure to detoxification enzyme inhibitors. Biochemical assays confirmed these results by showing significant elevated activities of cytochrome P450 monooxygenases (P450), glutathione S-transferases (GST) and carboxylesterases (CCE) in adults. Two kdr mutations, V1016G and F1534C, were detected by qPCR at low and high frequency, respectively, in all populations tested. A significant negative association between the two kdr mutations was detected. No significant association between kdr mutations frequency (for both 1534C and 1016G) and survival rate to DDT or permethrin (P > 0.05) was detected. Gene Copy Number Variations (CNV) were detected for particular detoxification enzymes. At the population level, the presence of CNV affecting the carboxylesterase CCEAE3A and the two cytochrome P450 CYP6BB2 and CYP6P12 were significantly correlated to insecticide resistance. These results suggest that both kdr mutations and metabolic resistance mechanisms are present in Laos but their impact on phenotypic resistance may differ in proportion at the population or individual level. Molecular analyses suggest that CNV affecting CCEAE3A previously associated with temephos resistance is also associated with malathion resistance while CNV affecting CYP6BB2 and CYP6P12 are associated with pyrethroid and possibly DDT resistance. The presence of high levels of insecticide resistance in the main arbovirus vector in Laos is worrying and may have important implications for dengue vector control in the country.
Sections du résumé
BACKGROUND
The yellow fever mosquito Aedes aegypti is the major vector of dengue, yellow fever, Zika, and Chikungunya viruses. Worldwide vector control is largely based on insecticide treatments but, unfortunately, vector control programs are facing operational challenges due to mosquitoes becoming resistant to commonly used insecticides. In Southeast Asia, resistance of Ae. aegypti to chemical insecticides has been documented in several countries but no data regarding insecticide resistance has been reported in Laos. To fill this gap, we assessed the insecticide resistance of 11 Ae. aegypti populations to larvicides and adulticides used in public health operations in the country. We also investigated the underlying molecular mechanisms associated with resistance, including target site mutations and detoxification enzymes putatively involved in metabolic resistance.
METHODS AND RESULTS
Bioassays on adults and larvae collected in five provinces revealed various levels of resistance to organophosphates (malathion and temephos), organochlorine (DDT) and pyrethroids (permethrin and deltamethrin). Synergist bioassays showed a significant increased susceptibility of mosquitoes to insecticides after exposure to detoxification enzyme inhibitors. Biochemical assays confirmed these results by showing significant elevated activities of cytochrome P450 monooxygenases (P450), glutathione S-transferases (GST) and carboxylesterases (CCE) in adults. Two kdr mutations, V1016G and F1534C, were detected by qPCR at low and high frequency, respectively, in all populations tested. A significant negative association between the two kdr mutations was detected. No significant association between kdr mutations frequency (for both 1534C and 1016G) and survival rate to DDT or permethrin (P > 0.05) was detected. Gene Copy Number Variations (CNV) were detected for particular detoxification enzymes. At the population level, the presence of CNV affecting the carboxylesterase CCEAE3A and the two cytochrome P450 CYP6BB2 and CYP6P12 were significantly correlated to insecticide resistance.
CONCLUSIONS
These results suggest that both kdr mutations and metabolic resistance mechanisms are present in Laos but their impact on phenotypic resistance may differ in proportion at the population or individual level. Molecular analyses suggest that CNV affecting CCEAE3A previously associated with temephos resistance is also associated with malathion resistance while CNV affecting CYP6BB2 and CYP6P12 are associated with pyrethroid and possibly DDT resistance. The presence of high levels of insecticide resistance in the main arbovirus vector in Laos is worrying and may have important implications for dengue vector control in the country.
Identifiants
pubmed: 31830027
doi: 10.1371/journal.pntd.0007852
pii: PNTD-D-19-00867
pmc: PMC6932826
doi:
Substances chimiques
Hydrocarbons, Chlorinated
0
Insecticides
0
Organophosphates
0
Pyrethrins
0
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0007852Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
PLoS Negl Trop Dis. 2017 Apr 5;11(4):e0005526
pubmed: 28379969
Parasit Vectors. 2014 Jan 15;7:25
pubmed: 24428880
Western Pac Surveill Response J. 2013 Mar 18;4(1):46-50
pubmed: 23908956
J Econ Entomol. 2007 Apr;100(2):545-50
pubmed: 17461081
Insect Biochem Mol Biol. 2016 Jul;74:61-7
pubmed: 27180726
Parasit Vectors. 2015 Jun 12;8:325
pubmed: 26068925
PLoS One. 2014 Jul 11;9(7):e101992
pubmed: 25013910
Acta Trop. 2008 Oct;108(1):54-7
pubmed: 18801327
Am J Trop Med Hyg. 2009 May;80(5):745-51
pubmed: 19407118
Med Vet Entomol. 2017 Dec;31(4):340-350
pubmed: 28752548
J Vector Ecol. 2011 Jun;36(1):204-12
pubmed: 21635659
PLoS Negl Trop Dis. 2014 Aug 28;8(8):e3085
pubmed: 25166902
PLoS Negl Trop Dis. 2014 Mar 20;8(3):e2743
pubmed: 24651719
PLoS One. 2014 Dec 31;9(12):e115569
pubmed: 25551768
PLoS Negl Trop Dis. 2015 May 22;9(5):e0003771
pubmed: 26000638
PLoS Negl Trop Dis. 2014 Jun 19;8(6):e2948
pubmed: 24945250
PLoS Negl Trop Dis. 2019 Jun 3;13(6):e0007432
pubmed: 31158225
Anal Biochem. 1976 May 7;72:248-54
pubmed: 942051
Western Pac Surveill Response J. 2014 Mar 31;5(1):7-13
pubmed: 24734212
Am J Trop Med Hyg. 2010 Aug;83(2):277-84
pubmed: 20682868
Parasit Vectors. 2018 Dec 3;11(1):616
pubmed: 30509299
Mol Ecol Resour. 2008 Jan;8(1):103-6
pubmed: 21585727
PLoS Negl Trop Dis. 2012;6(3):e1595
pubmed: 22479665
PLoS One. 2017 Dec 28;12(12):e0189879
pubmed: 29284012
PLoS One. 2017 Apr 24;12(4):e0175984
pubmed: 28437449
Parasit Vectors. 2018 Sep 26;11(1):526
pubmed: 30257701
PLoS Negl Trop Dis. 2009 Oct 06;3(10):e527
pubmed: 19806205
J Am Mosq Control Assoc. 1987 Jun;3(2):302-3
pubmed: 3333059
Asia Pac J Public Health. 2018 Mar;30(2):158-166
pubmed: 29502428
PLoS One. 2018 Oct 25;13(10):e0206387
pubmed: 30359425
Trans R Soc Trop Med Hyg. 2008 Jun;102(6):524-5
pubmed: 18295809
PLoS Negl Trop Dis. 2017 Jul 20;11(7):e0005625
pubmed: 28727779
Genome Res. 2015 Sep;25(9):1347-59
pubmed: 26206155
Acta Trop. 2011 Jan;117(1):31-8
pubmed: 20858454
Emerg Infect Dis. 1998 Oct-Dec;4(4):605-13
pubmed: 9866736
Parasit Vectors. 2013 Aug 30;6(1):253
pubmed: 24059267
BMC Genomics. 2009 Oct 26;10:494
pubmed: 19857255
Sci Rep. 2017 Apr 19;7:46549
pubmed: 28422157
Trop Med Int Health. 2011 Apr;16(4):501-9
pubmed: 21342372
Insects. 2015 Jul 23;6(3):658-85
pubmed: 26463408
Trop Med Int Health. 2009 Sep;14(9):1134-42
pubmed: 19563430
Parasit Vectors. 2016 Jul 26;9(1):417
pubmed: 27460671
Med Vet Entomol. 2008 Sep;22(3):203-21
pubmed: 18816269
Parasit Vectors. 2017 Jun 5;10(1):283
pubmed: 28583207
PLoS Negl Trop Dis. 2014 Jul 31;8(7):e3032
pubmed: 25077956
Nucleic Acids Res. 2001 May 1;29(9):e45
pubmed: 11328886
Infect Dis Poverty. 2017 Feb 10;6(1):38
pubmed: 28187780
Bull World Health Organ. 2001;79(11):1060-4
pubmed: 11731814
Nature. 2003 May 8;423(6936):136-7
pubmed: 12736674
Insect Biochem Mol Biol. 2004 Jul;34(7):653-65
pubmed: 15242706
Parasit Vectors. 2017 Mar 27;10(1):161
pubmed: 28347352
Med Vet Entomol. 2003 Mar;17(1):87-94
pubmed: 12680930
Trop Biomed. 2007 Jun;24(1):7-15
pubmed: 17568372
Sci Rep. 2016 Apr 20;6:24707
pubmed: 27094778
Bull World Health Organ. 1966;35(1):3-15
pubmed: 5297536
Parasitol Res. 2011 Sep;109(3):531-7
pubmed: 21336645
Insect Mol Biol. 2007 Dec;16(6):785-98
pubmed: 18093007
PLoS One. 2012;7(2):e30989
pubmed: 22363529