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Meta-Analysis
. 2021 May 24;5(5):CD012776.
doi: 10.1002/14651858.CD012776.pub3.

Piperonyl butoxide (PBO) combined with pyrethroids in insecticide-treated nets to prevent malaria in Africa

Katherine Gleave  1 , Natalie Lissenden  1 , Marty Chaplin  2 , Leslie Choi  1 , Hilary Ranson  1
Affiliations
Meta-Analysis

Piperonyl butoxide (PBO) combined with pyrethroids in insecticide-treated nets to prevent malaria in Africa

Katherine Gleave et al. Cochrane Database Syst Rev. .

Abstract

Background: Pyrethroid long-lasting insecticidal nets (LLINs) have been important in the large reductions in malaria cases in Africa, but insecticide resistance in Anopheles mosquitoes threatens their impact. Insecticide synergists may help control insecticide-resistant populations. Piperonyl butoxide (PBO) is such a synergist; it has been incorporated into pyrethroid-LLINs to form pyrethroid-PBO nets, which are currently produced by five LLIN manufacturers and, following a recommendation from the World Health Organization (WHO) in 2017, are being included in distribution campaigns. This review examines epidemiological and entomological evidence on the addition of PBO to pyrethroid nets on their efficacy.

Objectives: To compare effects of pyrethroid-PBO nets currently in commercial development or on the market with effects of their non-PBO equivalent in relation to: 1. malaria parasite infection (prevalence or incidence); and 2. entomological outcomes.

Search methods: We searched the Cochrane Infectious Diseases Group (CIDG) Specialized Register, CENTRAL, MEDLINE, Embase, Web of Science, CAB Abstracts, and two clinical trial registers (ClinicalTrials.gov and WHO International Clinical Trials Registry Platform) up to 25 September 2020. We contacted organizations for unpublished data. We checked the reference lists of trials identified by these methods.

Selection criteria: We included experimental hut trials, village trials, and randomized controlled trials (RCTs) with mosquitoes from the Anopheles gambiae complex or the Anopheles funestus group.

Data collection and analysis: Two review authors assessed each trial for eligibility, extracted data, and determined the risk of bias for included trials. We resolved disagreements through discussion with a third review author. We analysed data using Review Manager 5 and assessed the certainty of evidence using the GRADE approach.

Main results: Sixteen trials met the inclusion criteria: 10 experimental hut trials, four village trials, and two cluster-RCTs (cRCTs). Three trials are awaiting classification, and four trials are ongoing. Two cRCTs examined the effects of pyrethroid-PBO nets on parasite prevalence in people living in areas with highly pyrethroid-resistant mosquitoes (< 30% mosquito mortality in discriminating dose assays). At 21 to 25 months post intervention, parasite prevalence was lower in the intervention arm (odds ratio (OR) 0.79, 95% confidence interval (CI) 0.67 to 0.95; 2 trials, 2 comparisons; moderate-certainty evidence). In highly pyrethroid-resistant areas, unwashed pyrethroid-PBO nets led to higher mosquito mortality compared to unwashed standard-LLINs (risk ratio (RR) 1.84, 95% CI 1.60 to 2.11; 14,620 mosquitoes, 5 trials, 9 comparisons; high-certainty evidence) and lower blood feeding success (RR 0.60, 95% CI 0.50 to 0.71; 14,000 mosquitoes, 4 trials, 8 comparisons; high-certainty evidence). However, in comparisons of washed pyrethroid-PBO nets to washed LLINs, we do not know if PBO nets had a greater effect on mosquito mortality (RR 1.20, 95% CI 0.88 to 1.63; 10,268 mosquitoes, 4 trials, 5 comparisons; very low-certainty evidence), although the washed pyrethroid-PBO nets did decrease blood-feeding success compared to standard-LLINs (RR 0.81, 95% CI 0.72 to 0.92; 9674 mosquitoes, 3 trials, 4 comparisons; high-certainty evidence). In areas where pyrethroid resistance is moderate (31% to 60% mosquito mortality), mosquito mortality was higher with unwashed pyrethroid-PBO nets compared to unwashed standard-LLINs (RR 1.68, 95% CI 1.33 to 2.11; 751 mosquitoes, 2 trials, 3 comparisons; moderate-certainty evidence), but there was little to no difference in effects on blood-feeding success (RR 0.90, 95% CI 0.72 to 1.11; 652 mosquitoes, 2 trials, 3 comparisons; moderate-certainty evidence). For washed pyrethroid-PBO nets compared to washed standard-LLINs, we found little to no evidence for higher mosquito mortality or reduced blood feeding (mortality: RR 1.07, 95% CI 0.74 to 1.54; 329 mosquitoes, 1 trial, 1 comparison, low-certainty evidence; blood feeding success: RR 0.91, 95% CI 0.74 to 1.13; 329 mosquitoes, 1 trial, 1 comparison; low-certainty evidence). In areas where pyrethroid resistance is low (61% to 90% mosquito mortality), studies reported little to no difference in the effects of unwashed pyrethroid-PBO nets compared to unwashed standard-LLINs on mosquito mortality (RR 1.25, 95% CI 0.99 to 1.57; 948 mosquitoes, 2 trials, 3 comparisons; moderate-certainty evidence), and we do not know if there was any effect on blood-feeding success (RR 0.75, 95% CI 0.27 to 2.11; 948 mosquitoes, 2 trials, 3 comparisons; very low-certainty evidence). For washed pyrethroid-PBO nets compared to washed standard-LLINs, we do not know if there was any difference in mosquito mortality (RR 1.39, 95% CI 0.95 to 2.04; 1022 mosquitoes, 2 trials, 3 comparisons; very low-certainty evidence) or on blood feeding (RR 1.07, 95% CI 0.49 to 2.33; 1022 mosquitoes, 2 trials, 3 comparisons; low-certainty evidence). In areas where mosquito populations are susceptible to insecticides (> 90% mosquito mortality), there may be little to no difference in the effects of unwashed pyrethroid-PBO nets compared to unwashed standard-LLINs on mosquito mortality (RR 1.20, 95% CI 0.64 to 2.26; 2791 mosquitoes, 2 trials, 2 comparisons; low-certainty evidence). This is similar for washed nets (RR 1.07, 95% CI 0.92 to 1.25; 2644 mosquitoes, 2 trials, 2 comparisons; low-certainty evidence). We do not know if unwashed pyrethroid-PBO nets had any effect on the blood-feeding success of susceptible mosquitoes (RR 0.52, 95% CI 0.12 to 2.22; 2791 mosquitoes, 2 trials, 2 comparisons; very low-certainty evidence). The same applies to washed nets (RR 1.25, 95% CI 0.82 to 1.91; 2644 mosquitoes, 2 trials, 2 comparisons; low-certainty evidence). In village trials comparing pyrethroid-PBO nets to LLINs, there was no difference in sporozoite rate (4 trials, 5 comparisons) nor in mosquito parity (3 trials, 4 comparisons).

Authors' conclusions: In areas of high insecticide resistance, pyrethroid-PBO nets have greater entomological and epidemiological efficacy compared to standard LLINs, with sustained reduction in parasite prevalence, higher mosquito mortality and reduction in mosquito blood feeding rates 21 to 25 months post intervention. Questions remain about the durability of PBO on nets, as the impact of pyrethroid-PBO nets on mosquito mortality was not sustained over 20 washes in experimental hut trials, and epidemiological data on pyrethroid-PBO nets for the full intended three-year life span of the nets is not available. Little evidence is available to support greater entomological efficacy of pyrethroid-PBO nets in areas where mosquitoes show lower levels of resistance to pyrethroids.

Trial registration: ClinicalTrials.gov NCT03289663.

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Conflict of interest statement

KG has no known conflicts of interest. NL has acted as rapporteur since 2015 for the Innovative Vector Control Consortium (IVCC) at its External Scientific Advisory Committee (ESAC) meetings. MC has no known conflicts of interest. LC has no known conflicts of interest. HR has served on a WHO committee to consider the evidence for PBO nets in malaria control. Preparation of the background work presented at this WHO meeting was funded by the Global Fund for AIDS, TB, and Malaria. Although HR interacts regularly with bed net manufacturers through her own research and her previous role on IVCC's advisory panels, neither HR nor her research group have received direct funding from these companies.

Figures

1
1
Study flow diagram.
2
2
‘Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1: Commercial pyrethroid‐PBO nets versus commercial LLINs: village trials, Outcome 1: Parasite prevalence (pyrethroid‐PBO nets vs non‐PBO LLINs, latest end points in RCT)
1.2
1.2. Analysis
Comparison 1: Commercial pyrethroid‐PBO nets versus commercial LLINs: village trials, Outcome 2: Parasite prevalence (pyrethroid‐PBO nets vs non‐PBO LLINs, shown at 4 different time points)
1.3
1.3. Analysis
Comparison 1: Commercial pyrethroid‐PBO nets versus commercial LLINs: village trials, Outcome 3: Mosquito sporozoite‐positive (adjusted ICC 0.1)
1.4
1.4. Analysis
Comparison 1: Commercial pyrethroid‐PBO nets versus commercial LLINs: village trials, Outcome 4: Mosquito parous (adjusted ICC 0.1)
2.1
2.1. Analysis
Comparison 2: Commercial pyrethroid‐PBO nets versus commercial LLINs: hut trials, Outcome 1: Mosquito mortality (pooled) hut/night (adjusted ICC 0.1)
2.2
2.2. Analysis
Comparison 2: Commercial pyrethroid‐PBO nets versus commercial LLINs: hut trials, Outcome 2: Mosquito blood‐feeding success (pooled) hut/night (adjusted ICC 0.1)
2.3
2.3. Analysis
Comparison 2: Commercial pyrethroid‐PBO nets versus commercial LLINs: hut trials, Outcome 3: Mosquito exophily (pooled) hut/night (adjusted ICC 0.1)
2.4
2.4. Analysis
Comparison 2: Commercial pyrethroid‐PBO nets versus commercial LLINs: hut trials, Outcome 4: Mosquito mortality (high resistance) hut/night (adjusted ICC 0.1)
2.5
2.5. Analysis
Comparison 2: Commercial pyrethroid‐PBO nets versus commercial LLINs: hut trials, Outcome 5: Mosquito blood‐feeding success (high resistance) hut/night (adjusted ICC 0.1)
2.6
2.6. Analysis
Comparison 2: Commercial pyrethroid‐PBO nets versus commercial LLINs: hut trials, Outcome 6: Mosquito mortality (moderate resistance) hut/night (adjusted ICC 0.1)
2.7
2.7. Analysis
Comparison 2: Commercial pyrethroid‐PBO nets versus commercial LLINs: hut trials, Outcome 7: Mosquito blood‐feeding success (moderate resistance) hut/night (adjusted ICC 0.1)
2.8
2.8. Analysis
Comparison 2: Commercial pyrethroid‐PBO nets versus commercial LLINs: hut trials, Outcome 8: Mosquito mortality (low resistance) hut/night (adjusted ICC 0.1)
2.9
2.9. Analysis
Comparison 2: Commercial pyrethroid‐PBO nets versus commercial LLINs: hut trials, Outcome 9: Mosquito blood‐feeding success (low resistance) hut/night (adjusted ICC 0.1)
2.10
2.10. Analysis
Comparison 2: Commercial pyrethroid‐PBO nets versus commercial LLINs: hut trials, Outcome 10: Mosquito mortality (susceptible) hut/night (adjusted ICC 0.1)
2.11
2.11. Analysis
Comparison 2: Commercial pyrethroid‐PBO nets versus commercial LLINs: hut trials, Outcome 11: Mosquito blood‐feeding success (susceptible) hut/night (adjusted ICC 0.1)
2.12
2.12. Analysis
Comparison 2: Commercial pyrethroid‐PBO nets versus commercial LLINs: hut trials, Outcome 12: Mosquito mortality (high resistance/Permanet) hut/night (adjusted ICC 0.1)
2.13
2.13. Analysis
Comparison 2: Commercial pyrethroid‐PBO nets versus commercial LLINs: hut trials, Outcome 13: Mosquito blood‐feeding success (high resistance/Permanet) hut/night (adjusted ICC 0.1)
2.14
2.14. Analysis
Comparison 2: Commercial pyrethroid‐PBO nets versus commercial LLINs: hut trials, Outcome 14: Mosquito mortality (high resistance/Olyset) hut/night (adjusted ICC 0.1)
2.15
2.15. Analysis
Comparison 2: Commercial pyrethroid‐PBO nets versus commercial LLINs: hut trials, Outcome 15: Mosquito blood‐feeding success (high resistance/Olyset) hut/night (adjusted ICC 0.1)
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Awolola 2014 {published data only}
    1. Awolola ST, Adeogun AO, Olojede JB, Oduola AO, Oyewole IO, Amajoh CN. Impact of PermaNet 3.0 on entomological indices in an area of pyrethroid resistant Anopheles gambiae in south-western Nigeria. Parasites & Vectors 2014;7:236. [DOI: 10.1186/1756-3305-7-236] - DOI - PMC - PubMed
Bayili 2017 {published data only (unpublished sought but not used)}
    1. Bayili K. Phase II field evaluation of long-lasting nets DawaPlus 3.0 (deltamethrin and PBO in roof panel; deltamethrin alone in the side panels) and DawaPlus 4.0 (deltamethrin and PBO) of Tana Netting against natural populations of Anopheles gambiae s.l in Burkina Faso. Report of the twentieth WHOPES working group meeting, WHO/HQ, Geneva, 20–24 March 2017. http://apps.who.int/iris/bitstream/handle/10665/258921/WHO-HTM-NTD-WHOPE... (accessed 13 September 2017). [WHO/HTM/NTD/WHOPES/2017.04]
Cisse 2017 {published and unpublished data}
    1. Cisse MB, Sangare D, Oxborough RM, Dicko A, Dengela D, Sadou A, et al. A village level cluster-randomized entomological evaluation of combination long-lasting insecticidal nets containing pyrethroid plus PBO synergist in Southern Mali. Malaria Journal 2017;16:477. [DOI: 10.1186/s12936-017-2124-1] - DOI - PMC - PubMed
Corbel 2010 {published data only}
    1. Corbel V, Chabi J, Dabiré RK, Etang J, Nwane P, Pigeon O, et al. Field efficacy of a new mosaic long-lasting mosquito net (PermaNet 3.0) against pyrethroid-resistant malaria vectors: a multi centre study in Western and Central Africa. Malaria Journal 2010;9:113. [DOI: 10.1186/1475-2875-9-113] - DOI - PMC - PubMed
Koudou 2011 {published data only}
    1. Koudou BG, Koffi AA, Malone D, Hemingway J. Efficacy of PermaNet® 2.0 and PermaNet® 3.0 against insecticide-resistant Anopheles gambiae in experimental huts in Côte d’Ivoire. Malaria Journal 2011;10(1):172. [DOI: 10.1186/1475-2875-10-172] - DOI - PMC - PubMed
Menze 2020 {published and unpublished data}
    1. Menze B, Kouamo MF, Wondji MJ, Tchapga W, Tchoupo M, Kusimo MO, et al. An experimental hut evaluation of PBO-based and pyrethroid-only nets against the malaria vector Anopheles funestus reveals a loss of bed nets efficacy associated with GSTe2 metabolic resistance. Genes 2020;11(2):143. [DOI: 10.3390/genes11020143] - DOI - PMC - PubMed
Moore 2016 {published and unpublished data}
    1. Moore S. Field evaluation of an alpha-cypermethrin+PBO long-lasting insecticidal net (Veeralin LN) against natural populations of Anopheles arabiensis in experimental huts, Tanzania [Unpublished report to the WHO Pesticide Evaluation Scheme (WHOPES)]. Report of the nineteenth WHOPES working group meeting: WHO/HQ, Geneva, 8–11 February 2016. http://apps.who.int/iris/bitstream/handle/10665/205588/9789241510400_eng... (accessed 24 August 2017). [WHO/HTM/NTD/WHOPES/2016.2]
Mzilahowa 2014 {unpublished data only}
    1. Mzilahowa T, Luka M, Chiumia M, Gimnig J. Efficacy of the PermaNet 3.0 and the Olyset Plus against pyrethroid resistant An funestus and An arabiensis (as supplied 14 March 2015). Data on file (received 14 March 2015).
N'Guessan 2010 {published data only}
    1. N’Guessan R, Asidi A, Boko P, Odjo A, Akogbeto M, Pigeon O, et al. An experimental hut evaluation of PermaNet(®) 3.0, a deltamethrin-piperonyl butoxide combination net, against pyrethroid-resistant Anopheles gambiae and Culex quinquefasciatus mosquitoes in southern Benin. Transactions of the Royal Society of Tropical Medicine and Hygiene 2010;104(12):758-65. [DOI: 10.1016/j.trstmh.2010.08.008] - DOI - PubMed
Oumbouke 2019 {published data only}
    1. Oumbouke WA, Rowland M, Koffi AA, Alou LPA, Camara S, N’Guessan R. Evaluation of an alpha-cypermethrin + PBO mixture long-lasting insecticidal net VEERALIN® LN against pyrethroid resistant Anopheles gambiae s.s.: an experimental hut trial in M’bé, central Côte d’Ivoire. Parasites & Vectors 2019;12(1):544. [DOI: 10.1186/s13071-019-3796-x] - DOI - PMC - PubMed
Pennetier 2013 {published data only}
    1. Pennetier C, Bouraima A, Chandre F, Piameu M, Etang J, Rossignol M, et al. Efficacy of Olyset(R) Plus, a new long-lasting insecticidal net incorporating permethrin and piperonyl-butoxide against multi-resistant malaria vectors [corrected]. PLoS One 2013;8(10):e75134. [DOI: 10.1371/journal.pone.0075134] - DOI - PMC - PubMed
Protopopoff 2018 {published data only}
    1. Protopopoff N, Charlwood D, Mosha J, Wright A, Kisinza W, Mosha F, et al. Evaluation of a novel long lasting insecticidal net to indoor residual spray product, separately to together, against malaria transmitted by pyrethroid resistant mosquitoes in northwest Tanzania: a cluster randomized controlled trial. Lancet 2018;391(10130):1577-88. [DOI: 10.1016/S0140-6736(18)30427-6] - DOI - PMC - PubMed
Staedke 2020 {published and unpublished data}
    1. ISRCTN17516395. Impact of long-lasting insecticide treated bednets with and without piperonyl butoxide (PBO) on malaria indicators in Uganda. www.isrctn.com/ISRCTN17516395 (accessed 24 August 2018).
    1. 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(10232):1292-303. [DOI: 10.1016/S0140-6736(20)30214-2] - DOI - PMC - PubMed
Stiles‐Ocran 2013 {unpublished data only}
    1. Stiles-Ocran J. Field evaluation of PermaNet® 3.0 in controlling pyrethroid resistant Anopheles gambiae in the Chirano Area, Western Region, Ghana (as supplied 12 March 2015). Data on file 2013.
Toé 2018 {published and unpublished data}
    1. Toé KH, Müller P, Badolo A, Traore A, Sagnon N, Dabiré RK, et al. Do bednets including piperonyl butoxide offer additional protection against populations of Anopheles gambiae s.l. that are highly resistant to pyrethroids? An experimental hut evaluation in Burkina Faso. Medical and Veterinary Entomology 2018;32(4):407-16. [DOI: 10.1111/mve.12316] - DOI - PubMed
Tungu 2010 {published data only}
    1. Tungu P, Magesa S, Maxwell C, Malima R, Masue D, Sudi W, et al. Evaluation of PermaNet 3.0 a deltamethrin-PBO combination net against Anopheles gambiae and pyrethroid resistant Culex quinquefasciatus mosquitoes: an experimental hut trial in Tanzania. Malaria Journal 2010;9:21. [DOI: 10.1186/1475-2875-9-21] - DOI - PMC - PubMed

References to studies excluded from this review

Darriet 2011 {published data only}
    1. Darriet F, Chandre F. Combining piperonyl butoxide and dinotefuran restores the efficacy of deltamethrin mosquito nets against resistant Anopheles gambiae (Diptera: Culicidae). Journal of Medical Entomology 2011;48(4):952-5. [DOI: 10.1603/ME11022] - DOI - PubMed
Darriet 2013 {published data only}
    1. Darriet F, Chandre F. Efficacy of six neonicotinoid insecticides alone and in combination with deltamethrin and piperonyl butoxide against pyrethroid-resistant Aedes aegypti and Anopheles gambiae (Diptera: Culicidae). Pest Management Science 2013;69(8):905-10. [DOI: 10.1002/ps.3446] - DOI - PubMed

References to studies awaiting assessment

Koudou 2012 {unpublished data only}
    1. Koudou B, Malone D. Does PermaNet® 3.0 protect against pyrethroid resistant mosquitoes? Manuscript in preparation for Acta Tropica (received 14 December 2012).
Shono 2017 {published data only}
    1. Shono Y, Ohashi K, Lucas JR. Biological performance of Olyset® Plus, a long-lasting mosquito net incorporating a mixture of a pyrethroid and synergist. Acta Horticulturae 2017;1169:77-81.
Tungu 2017 {published data only (unpublished sought but not used)}
    1. Tungu P. Phase II study to evaluate the efficacy and wash resistance of DawaPlus 3.0 and DawaPlus 4.0 against natural populations of Anopheles funestus s.s. in experimental huts in Muheza, Tanzania. Report of the twentieth WHOPES working group meeting, WHO/HQ, Geneva, 20–24 March 2017. http://apps.who.int/iris/bitstream/handle/10665/258921/WHO-HTM-NTD-WHOPE... (accessed 13 September 2017). [WHO/HTM/NTD/WHOPES/2017.04]

References to ongoing studies

ISRCTN99611164 {unpublished data only}
    1. ISRCTN99611164. Comparative evaluation of standard and dual-treated insecticide bednets in Sud Ubangi, Democratic Republic of Congo. https://doi.org/10.1186/ISRCTN99611164 (accessed prior to 1 May 2021).
NCT03289663 {unpublished data only}
    1. NCT03289663. Effectiveness study of bednets treated with synergistic combination of insecticides in an area with pyrethroid-resistant vectors in the Democratic Republic of the Congo [Effectiveness study of new generation bednets in the context of conventional insecticide resistance in the Democratic Republic of Congo]. clinicaltrials.gov/show/NCT03289663 (first received 24 August 2018).
NCT04182126 {unpublished data only}
    1. NCT04182126. Environmental modifications in sub-Saharan Africa: changing epidemiology, transmission and pathogenesis of Plasmodium falciparum and P. vivax malaria [HS#2017-3512, adaptive interventions for optimizing malaria control: a cluster-randomized SMART trial]. clinicaltrials.gov/ct2/show/NCT04182126 (first received 2 December 2019).
UMIN000019971 {unpublished data only}
    1. Minakawa N, Kongere JO, Sonye GO, Lutiali PA, Awuor B, Kawada H, et al. A preliminary study on designing a cluster randomized control trial of two new mosquito nets to prevent malaria parasite infection. Tropical Medicine and Health 2020;48(1):98. [DOI: 10.1186/s41182-020-00276-x] - DOI - PMC - PubMed
    1. UMIN000019971. Effects of long lasting insecticidal nets incorporating piperonyl butoxidae on malaria transmission among children: a cluster randomized controlled field trial. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R00002... (first posted 25 December 2015).

Additional references

Abílio 2015
    1. Abílio AP, Marrune P, Deus N, Mbofana F, Muianga P, Kampango A. Bio-efficacy of new long-lasting insecticide-treated bed nets against Anopheles funestus and Anopheles gambiae from central and northern Mozambique. Malaria Journal 2015;14:352. [DOI: 10.1186/s12936-015-0885-y] - DOI - PMC - PubMed
Adeogun 2012
    1. Adeogun AO, Olojede JB, Oduola AO, Awolola TS. Efficacy of a combination long lasting insecticidal net (PermaNet® 3.0) against pyrethroid resistant Anopheles gambiae s.s. and Culex quinquefasciatus: an experimental hut trial in Nigeria. Nigerian Journal of Clinical & Biomedical Research 2012;6:37-50.
Aïzoun 2013
    1. Aïzoun N, Ossè R, Azondekon R, Alia R, Oussou O, Gnanguenon V, et al. Comparison of the standard WHO susceptibility tests and the CDC bottle bioassay for the determination of insecticide susceptibility in malaria vectors and their correlation with biochemical and molecular biology assays in Benin, West Africa. Parasites & Vectors 2013;6:147. - PMC - PubMed
Bhatt 2015
    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(7572):207-11. - PMC - PubMed
Bobanga 2013
    1. Bobanga T, Ayieko W, Zanga M, Umesumbu S, Landela A, Fataki O, et al. Field efficacy and acceptability of PermaNet® 3.0 and OlysetNet® in Kinshasa, Democratic Republic of the Congo. Journal of Vector Borne Diseases 2013;50(3):206-14. - PubMed
Churcher 2016
    1. Churcher TS, Lissenden N, Griffin JT, Worrall E, Ranson H. The impact of pyrethroid resistance on the efficacy and effectiveness of bednets for malaria control in Africa. eLife 2016;5:e16090. [DOI: ] - PMC - PubMed
Deeks 2017
    1. Deeks JJ, Higgins JP, Altman DG (editors), on behalf of the Cochrane Statistical Methods Group. Chapter 9. Analysing data and undertaking meta-analyses. In: Higgins JP, Churchill R, Chandler J, Cumpston MS (editors). Cochrane Handbook for Systematic Reviews of Interventions version 5.2.0 (updated June 2017), Cochrane, 2017. Available from www.training.cochrane.org/handbook.
Djègbè 2011
    1. Djègbè I, Boussari O, Sidick A, Martin T, Ranson H, Chandre F, et al. Dynamics of insecticide resistance in malaria vectors in Benin: first evidence of the presence of L1014S kdr mutation in Anopheles gambiae from West Africa. Malaria Journal 2011;10:261. - PMC - PubMed
GRADEpro GDT 2015 [Computer program]
    1. McMaster University (developed by Evidence Prime) GRADEpro GDT. Version accessed 5 May 2017. Hamilton (ON): McMaster University (developed by Evidence Prime), 2015. Available at gradepro.org.
Hawley 2003
    1. Hawley WA, Phillips-Howard PA, ter Kuile FO, Terlouw DJ, Vulule JM, Ombok M, et al. Community-wide effects of permethrin-treated bed nets on child mortality and malaria morbidity in western Kenya. American Journal of Tropical Medicine & Hygiene 2003;68(4 Suppl):121-7. [DOI: 10.4269/ajtmh.2003.68.121] - DOI - PubMed
Higgins 2003
    1. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-60. - PMC - PubMed
Higgins 2011
    1. Higgins JP, Deeks JJ, Altman DG, Cochrane Statistical Methods Group. Chapter 16. Special topics in statistics. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0 (updated March 2011), The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Higgins 2017
    1. Higgins JP, Altman DG, Sterne JA (editors). Chapter 8. Assessing risk of bias in included studies. In: Higgins JP, Churchill R, Chandler J, Cumpston MS (editors). Cochrane Handbook for Systematic Reviews of Interventions version 5.2.0 (updated June 2017), Cochrane, 2017. Available from www.training.cochrane.org/handbook.
Killeen 2018
    1. Killeen G, Ranson H. Insecticide-resistant malaria vectors must be tackled. Lancet 2018;391(10130):1551-2. - PubMed
Kleinschmidt 2018
    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 2018;18:20172-5. [DOI: 10.1016/S1473-3099(18)30172-5] - DOI - PMC - PubMed
Lengeler 2004
    1. Lengeler C. Insecticide-treated bed nets and curtains for preventing malaria. Cochrane Database of Systematic Reviews 2004, Issue 2. Art. No: CD000363. [DOI: 10.1002/14651858.CD000363.pub2] - DOI - PubMed
Maxwell 2002
    1. Maxwell CA, Msuya E, Sudi M, Njunwa KJ, Carneiro IA, Curtis CF. Effect of community-wide use of insecticide-treated nets for 3-4 years on malarial morbidity in Tanzania. Tropical Medicine & International Health 2002;7(12):1003-8. [DOI: 10.1046/j.1365-3156.2002.00966] - DOI - PubMed
Mitchell 2012
    1. Mitchell SN, Stevenson BJ, Müller P, Wilding CS, Egyir-Yawson A, Field SG, et al. Identification and validation of a gene causing cross-resistance between insecticide classes in Anopheles gambiae from Ghana. Proceedings of the Nationall Academy of Sciences of the United States of America 2012;109(16):6147-52. [DOI: 10.1073/pnas.1203452109] - DOI - PMC - PubMed
MPAC 2016
    1. Malaria Policy Advisory Committee. WHO Malaria Policy Advisory Committee (MPAC) meeting report (September 2016). www.who.int/malaria/publications/atoz/mpac-september2016-report.pdf?ua=1 (accessed 1 May 2017).
N'Guessan 2007
    1. N'Guessan R, Corbel V, Akogbéto M, Rowland M. Reduced efficacy of insecticide-treated nets and indoor residual spraying for malaria control in pyrethroid resistance area, Benin. Emerging Infectious Diseases 2007;13(2):199-206. [DOI: 10.3201/eid1302.060631] - DOI - PMC - PubMed
Parker 2015
    1. Parker J, Angarita-Jaimes N, Abe M, Towers CE, Towers D, McCall P. Infrared video tracking of Anopheles gambiae at insecticide-treated bed nets reveals rapid decisive impact after brief localised net contact. Scientific Reports 2015;5:e13392. - PMC - PubMed
PMI 2018
    1. PMI. U.S. President’s Malaria Initiative technical guidance, 2018. www.pmi.gov/docs/default-source/default-document-library/tools-curricula....
Ranson 2011
    1. Ranson H, N'Guessan R, Lines J, Moiroux N, Nkuni Z, Corbel V. Pyrethroid resistance in African Anopheline mosquitoes: what are the implications for malaria control? Trends in Parasitology 2011;27(2):91-8. [DOI: 10.1016/j.pt.2010.08.004] - DOI - PubMed
Ranson 2016
    1. Ranson H, Lissenden N. Insecticide resistance in African Anopheles mosquitoes: a worsening situation that needs urgent action to maintain malaria control. Trends in Parasitology 2016;32(3):187-96. [DOI: 10.1016/j.pt.2015.11.010] - DOI - PubMed
Review Manager 2014 [Computer program]
    1. Nordic Cochrane Centre, The Cochrane Collaboration Review Manager 5 (RevMan 5). Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Ridl 2008
    1. Ridl FC, Bass C, Torrez M, Govender D, Ramdeen V, Yellot L, et al. A pre-intervention study of malaria vector abundance in Rio Muni, Equatorial Guinea: their role in malaria transmission and the incidence of insecticide resistance alleles. Malaria Journal 2008;7:194. [DOI: 10.1186/1475-2875-7-194] - DOI - PMC - PubMed
Riveron 2015
    1. Riveron JM, Chiumia M, Menze BD, Barnes KG, Irving H, Ibrahim SS, et al. Rise of multiple insecticide resistance in Anopheles funestus in Malawi: a major concern for malaria vector control. Malaria Journal 2015;14:344. [DOI: 10.1186/s12936-015-0877-y] - DOI - PMC - PubMed
Schünemann 2013
    1. Schünemann H, Brożek J, Guyatt G, Oxman A, editor(s). Handbook for grading the quality of evidence and the strength of recommendations using the GRADE approach (updated October 2013). GRADE Working Group, 2013. Available from gdt.guidelinedevelopment.org/app/handbook/handbook.html.
Stevenson 2011
    1. Stevenson BJ, Bibby J, Pignatelli P, Muangnoicharoen S, O'Neill PM, Lian LY, et al. Cytochrome P450 6M2 from the malaria vector Anopheles gambiae metabolizes pyrethroids: sequential metabolism of deltamethrin revealed. Insect Biochemistry and Molecular Biology 2011;41(7):492-502. [DOI: 10.1016/j.ibmb.2011.02.003] - DOI - PubMed
Strode 2014
    1. Strode C, Donegan S, Garner P, Enayati AA, Hemingway J. The impact of pyrethroid resistance on the efficacy of insecticide-treated bed nets against African Anopheline mosquitoes: systematic review and meta-analysis. PLoS Medicine 2014;11(3):e1001619. [DOI: 10.1371/journal.pmed.1001619] - DOI - PMC - PubMed
Sumitomo 2013
    1. Sumitomo Chemical Co Ltd. Olyset Plus Technical Brochure 2013. sumivector.com/sites/default/files/site-content/pdf/Olyset_Plus_Technica... (accessed 1 May 2017).
Vestergaard 2015
    1. Vestergaard. Technical basis for deployment of PermaNet® 3.0 in areas with pyrethroid-resistant malaria vectors. PermaNet® 3.0 Technical Brochure. January 2015. www.vestergaard.com/images/pdf/PN3_Tech_Eng_2015.pdf (accessed 1 May 2017).
WHO 2013
    1. World Health Organization Pesticide Evaluation Scheme. Guidelines for laboratory and field testing of long-lasting insecticidal nets. apps.who.int/iris/bitstream/10665/80270/1/9789241505277_eng.pdf (accessed 24 August 2018).
WHO 2016
    1. World Health Organization. Test Procedures for Insecticide Resistance Monitoring in Malaria Vector Mosquitoes. Second edition. Geneva: WHO, 2016.
WHO 2017
    1. World Health Organization/Department of Control of Neglected Tropical Diseases. Design of epidemiological trials for vector control products, Report of a WHO Expert Advisory Group; Château de Penthes, Geneva, 24–25 April 2017. www.who.int/neglected_diseases/vector_ecology/resources/WHO_HTM_NTD_VEM_... (accessed 11 July 2017).
WHO 2019a
    1. World Health Organization. World malaria report 2019. www.who.int/malaria/publications/world_malaria_report/en/.
WHO 2019b
    1. World Health Organization. Guidelines for malaria vector control. https://apps.who.int/iris/bitstream/handle/10665/310862/9789241550499-en... (accessed prior to 13 May 2021).
WHO‐GMP 2015
    1. World Health Organization Global Malaria Programme. Conditions for use of long-lasting insecticidal nets treated with a pyrethroid and piperonyl butoxide. www.who.int/malaria/areas/vector_control/use-of-pbo-treated-llins-report... (accessed 24 August 2018).
WHO‐GMP 2017a
    1. World Health Organization. Conditions for deployment of mosquito nets treated with a pyrethroid and piperonyl butoxide. apps.who.int/iris/bitstream/handle/10665/258939/WHO-HTM-GMP-2017.17-eng.... (accessed 24 August 2018).
WHO‐GMP 2017b
    1. World Health Organization. The evaluation process for vector control products. www.who.int/malaria/publications/atoz/evaluation-process-vector-control-... (accessed 24 August 2018).
WHO‐GMP 2017c
    1. World Health Organization Global Malaria Programme. Malaria vector control policy recommendations and their applicability to product evaluation. www.who.int/malaria/publications/atoz/vector-control-recommendations/en/ (accessed 24 August 2018).
WHOPES 2016
    1. WHO/Department of Control of Neglected Tropical Diseases. Report of the nineteenth WHOPES working group meeting: WHO/HQ, Geneva, 8–11 February 2016. Review of Veeralin LN, VectoMax GR, Bactivec SC. apps.who.int/iris/bitstream/10665/205588/1/9789241510400_eng.pdf (accessed 1 May 2017).
Yewhalaw 2012
    1. Yewhalaw D, Asale A, Tushune K, Getachew Y, Duchateau L, Speybroeck N. Bio-efficacy of selected long-lasting insecticidal nets against pyrethroid resistant Anopheles arabiensis from South-Western Ethiopia. Parasites & Vectors 2012;5:159. [DOI: 10.1186/1756-3305-5-159] - DOI - PMC - PubMed
Zaim 2000
    1. Zaim M, Aitio A, Nakashima N. Safety of pyrethroid-treated mosquito nets. Medical and Veterinary Entomology 2000;14(1):1-5. - PubMed

References to other published versions of this review

Gleave 2017
    1. Gleave K, Lissenden N, Richardson M, Ranson H. Piperonyl butoxide (PBO) combined with pyrethroids in long-lasting insecticidal nets (LLINs) to prevent malaria in Africa. Cochrane Database of Systematic Reviews 2017, Issue 8. Art. No: CD012776. [DOI: 10.1002/14651858.CD012776] - DOI
Gleave 2018
    1. Gleave K, Lissenden N, Richardson M, Choi L, Ranson H. Piperonyl butoxide (PBO) combined with pyrethroids in insecticide-treated nets to prevent malaria in Africa. Cochrane Database of Systematic Reviews 2018, Issue 11. Art. No: CD012776. [DOI: 10.1002/14651858.CD012776.pub2] - DOI - PMC - PubMed

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