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. 2019 Mar 12;12(1):94.
doi: 10.1186/s13071-019-3353-7.

LLIN Evaluation in Uganda Project (LLINEUP): a cross-sectional survey of species diversity and insecticide resistance in 48 districts of Uganda

Amy Lynd  1 , Samuel Gonahasa  2 , Sarah G Staedke  3 , Ambrose Oruni  4 , Catherine Maiteki-Sebuguzi  2   5 , Grant Dorsey  6 , Jimmy Opigo  5 , Adoke Yeka  2 , Agaba Katureebe  2 , Mary Kyohere  2 , Janet Hemingway  4 , Moses R Kamya  2 , Martin J Donnelly  4
Affiliations

LLIN Evaluation in Uganda Project (LLINEUP): a cross-sectional survey of species diversity and insecticide resistance in 48 districts of Uganda

Amy Lynd et al. Parasit Vectors. .

Abstract

Background: Long-lasting insecticidal nets (LLINs) are the principal tool for malaria control in Africa and are presently treated with a single class of insecticide; however, increasing levels of insecticide resistance threaten their success. In response to this threat nets have been developed that incorporate the synergist, piperonyl butoxide (PBO), which inhibits the activity of cytochrome P450s which is one main mechanisms of insecticide resistance, allowing resistance to pyrethroids to be reversed. However, data on the value and cost effectiveness of these nets is lacking. A large-scale cluster randomised trial of conventional LLINs and PBO-LLINs was conducted in Uganda in 104 health sub-districts (HSDs) in 2017-2019. Prior to the mass distribution of LLINs, a baseline entomological survey was carried out, the results of which are reported herein. Ten households from each HSD were randomly selected for entomological surveillance at baseline which included household mosquito collections.

Results: Prior to LLIN distribution entomological collections were carried out in 1029 houses across the 104 HSDs. Anopheles gambiae (s.l.) was the principal vector in all but 9 of the 71 HSDs that yielded vector species. Molecular analysis found An. gambiae (s.s.) to be the predominant vector collected. Plasmodium falciparum was detected in 5.5% of An. gambiae (s.s.) and in 4.0% of An. funestus (s.s.) examined. Infection rates of other plasmodium species (P. vivax, P. ovale and P. malariae) were lower with infection rates of 1.2% and 1.7% for An. gambiae (s.s.) and An. funestus (s.s.), respectively. The knockdown resistance (kdr) mutation Vgsc-L1014S was found at very high frequency in An. gambiae (s.s.) with the Vgsc-L1014F mutation at low frequency and the wild-type allele virtually absent. In An. arabiensis the wild-type allele was predominant. The resistance-associated alleles, Cyp4j5-L43F and Coeae1d were found at moderate frequencies which varied across the study site. Vgsc-N1575Y mutation was not found in any samples examined.

Conclusions: No significant differences between planned intervention arms was observed in vector densities, sporozoite infection rate or insecticide resistance marker frequency across the study site prior to the distribution of LLINs. Very high levels of kdr resistance were observed in all areas; however, the resistance-associated markers Cyp4j5-L43F and Coeae1d were found at varying frequencies across the study site which may have implications for the effectiveness of standard LLINs. Trial registration This study is registered with ISRCTN, ISRCTN17516395. Registered 14 February 2017, http://www.isrctn.com/ISRCTN17516395.

Keywords: Cluster-randomised trial; Insecticide resistance; Long-lasting insecticidal nets (LLINs); Malaria; Piperonyl butoxide (PBO); Uganda; Vector control.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Mean mosquito density per house for Anopheles gambiae (s.l.) (a) and Anopheles funestus (s.l.) (b). c Relative proportion of Anopheles gambiae (s.l.), to total anophelines. d Box whisker plots illustrating the density of female An. gambiae (s.l.) by arm and region
Fig. 2
Fig. 2
Sporozoite infection rates. a P. falciparum sporozoite infection rate in Anopheles. b Sporozoite infection rate for combined P. vivax, P. ovale and P. malariae in Anopheles. c P. falciparum sporozoite infection rate in An. gambiae (s.s.) by net distribution arm. d Sporozoite infection rate for the combined P. vivax, P. ovale and P. malariae (P.OVM) in An. gambiae (s.s.) by net distribution arm. e P. falciparum sporozoite infection rate in An. funestus (s.s.) by net distribution arm. f Sporozoite infection rate for combined P. vivax, P. ovale and P. malariae (P. OVM) in An. funestus (s.s.) by net distribution arm
Fig. 3
Fig. 3
Resistance and polytene chromosome allele frequencies in Anopheles gambiae (s.s.) by net distribution arm. a Vgsc 1014F/S. b Cyp4j5-L43F. c Coeae1d. d 2La inversion
Fig. 4
Fig. 4
Resistance and polytene chromosome allele frequencies in Anopheles gambiae (s.s.). a Vgsc-1014S. b Vgsc-1014F. c Vgsc-1014L. d Cyp4j5-L43F. e 2La inversion. f Coeae1d
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References

    1. 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;526:207–211. doi: 10.1038/nature15535. - DOI - PMC - PubMed
    1. WHO . Global report on insecticide resistance in malaria vectors: 2010–2016. Geneva: World Health Organization; 2018.
    1. Hemingway J, Ranson H, Magill A, Kolaczinski J, Fornadel C, Gimnig J, et al. Averting a malaria disaster: will insecticide resistance derail malaria control? Lancet. 2016;387:1785–1788. doi: 10.1016/S0140-6736(15)00417-1. - DOI - PMC - PubMed
    1. Glunt KD, Coetzee M, Huijben S, Koffi AA, Lynch PA, N’Guessan R, et al. Empirical and theoretical investigation into the potential impacts of insecticide resistance on the effectiveness of insecticide-treated bed nets. Evol Appl. 2018;11:431–441. doi: 10.1111/eva.12574. - DOI - PMC - PubMed
    1. Kleinschmidt I, Bradley J, Knox TB, Mnzava AP, Kafy HT, Mbogo C, et al. Implications of insecticide resistance for malaria vector control with long-lasting insecticidal nets: a WHO-coordinated, prospective, international, observational cohort study. Lancet Infect Dis. 2018;18:640–649. doi: 10.1016/S1473-3099(18)30172-5. - DOI - PMC - PubMed

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