Jones, Christopher ORCID: https://orcid.org/0000-0002-6504-6224, Haji, Khamis A, Khatib, Bakari O, Bagi, Judit, Mcha, Juma, Devine, Gregor J, Daley, Matthew, Kabula, Bilali, Ali, Abdullah S, Majambere, Silas and Ranson, Hilary ORCID: https://orcid.org/0000-0003-2332-8247 (2013) 'The dynamics of pyrethroid resistance in Anopheles arabiensis from Zanzibar and an assessment of the underlying genetic basis'. Parasites & Vectors, Vol 6, e343.
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Abstract
Background
The emergence of pyrethroid resistance in the malaria vector, Anopheles arabiensis, threatens to undermine the considerable gains made towards eliminating malaria on Zanzibar. Previously, resistance was restricted to the island of Pemba while mosquitoes from Unguja, the larger of the two islands of Zanzibar, were susceptible. Here, we characterised the mechanism(s) responsible for resistance on Zanzibar using a combination of gene expression and target-site mutation assays.
Methods
WHO resistance bioassays were conducted using 1-5d old adult Anopheles gambiae s.l. collected between 2011 and 2013 across the archipelago. Synergist assays with the P450 inhibitor piperonyl-butoxide were performed in 2013. Members of the An. gambiae complex were PCR-identified and screened for target-site mutations (kdr and Ace-1). Gene expression in pyrethroid resistant An. arabiensis from Pemba was analysed using whole-genome microarrays.
Results
Pyrethroid resistance is now present across the entire Zanzibar archipelago. Survival to the pyrethroid lambda-cyhalothrin in bioassays conducted in 2013 was 23.5-54.3% on Unguja and 32.9-81.7% on Pemba. We present evidence that resistance is mediated, in part at least, by elevated P450 monoxygenases. Whole-genome microarray scans showed that the most enriched gene terms in resistant An. arabiensis from Pemba were associated with P450 activity and synergist assays with PBO completely restored susceptibility to pyrethroids in both islands. CYP4G16 was the most consistently over-expressed gene in resistant mosquitoes compared with two susceptible strains from Unguja and Dar es Salaam. Expression of this P450 is enriched in the abdomen and it is thought to play a role in hydrocarbon synthesis. Microarray and qPCR detected several additional genes putatively involved in this pathway enriched in the Pemba pyrethroid resistant population and we hypothesise that resistance may be, in part, related to alterations in the structure of the mosquito cuticle. None of the kdr target-site mutations, associated with pyrethroid/DDT resistance in An. gambiae elsewhere in Africa, were found on the islands.
Conclusion
The consequences of this resistance phenotype are discussed in relation to future vector control strategies on Zanzibar to support the ongoing malaria elimination efforts on the islands.
Item Type: | Article |
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Additional Information: | The electronic version of this article is the complete one and can be found online at: http://www.parasitesandvectors.com/content/6/1/343 |
Subjects: | QU Biochemistry > Genetics > QU 500 Genetic phenomena QX Parasitology > Insects. Other Parasites > QX 515 Anopheles QX Parasitology > Insects. Other Parasites > QX 600 Insect control. Tick control WA Public Health > Preventive Medicine > WA 240 Disinfection. Disinfestation. Pesticides (including diseases caused by) |
Faculty: Department: | Biological Sciences > Vector Biology Department |
Digital Object Identifer (DOI): | https://doi.org/10.1186/1756-3305-6-343 |
Depositing User: | Martin Chapman |
Date Deposited: | 28 Apr 2014 12:17 |
Last Modified: | 07 Jun 2022 11:09 |
URI: | https://archive.lstmed.ac.uk/id/eprint/3647 |
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