Clinical trial NCT03554616: Efficacy of Three Novel Bi-treated Long Lasting Insecticidal Nets
Official title: Efficacy of Three Different Bi-treated Long Lasting Insecticidal Nets and Deployment Strategy for Control of Malaria Transmitted by Pyrethroid Resistant Vectors: A Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Malaria
Anaemia
Keywords: Malaria
Vector Control
Long lasting Insecticidal Net
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
Collaborators: name: Kilimanjaro Christian Medical Centre, Tanzania
name: National Institute for Medical Research, Tanzania
name: University of Ottawa
First posted: 2018-06-13
Enrollment: 4200
Sex: ALL
Minimum age (years): 6
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The massive scale-up of Long Lasting Insecticidal Nets (LLIN) has led to a major reduction in malaria burden (up to 50%) in many sub-Saharan African countries. This progress is threatened by the wide scale selection of insecticide resistant malaria vectors. New types of LLIN combining a mixture of two insecticides or an insecticide and a synergist have been developed to control resistant mosquitoes.

The efficacy of three bi-treated LLIN are compared to a standard LLIN in a four-arm, single blinded, cluster-randomized trial in Misungwi district, Tanzania. The arms are; 1/ Royal Guard, a net combining pyriproxyfen (PPF), which is known to disrupt female reproduction and fertility of eggs, and the pyrethroid alpha-cypermethrin, 2/Interceptor G2, LLIN incorporating a mixture of two adulticides with different modes of action; chlorfenapyr and a pyrethroid (alpha-cypermethrin), and 3/ Olyset Plus an LLIN which incorporates a synergist, piperonyl butoxide (PBO), to enhance the potency of pyrethroid insecticides, and 4/ The control arm: Interceptor treated a standard LLIN treated with alpha-cypermethrin.

The primary outcome of the trial will be cross-sectional community prevalence of malaria infection (by RDT) in children aged 6 months to 14 years at 12 and 24 months post-intervention.


Eligibility criteria: Inclusion Criteria:

* At least one child between 6 months to 14 years old having permanent residence in selected household
* Having an adult caregiver willing to provide written consent for the household and clinical survey

Exclusion Criteria:

* Dwelling not found or vacant during the survey
* No adult caregiver capable to give informed consent
* Children severely ill

Primary outcomes:
measure: Malaria infection prevalence in children 6 months to 14 years
timeFrame: 24 months post intervention
Secondary outcomes:
measure: Incidence of malaria cases in children 6 months to 10 years
timeFrame: Two years post intervention follow up
measure: Prevalence of anaemia in children under 5 years old
timeFrame: 12, 18, 24, 30, 36 months post intervention
measure: Indoor Anopheles density
timeFrame: Three years post intervention follow up
measure: Sporozoite rate
timeFrame: Three years post intervention follow up
measure: Insecticide content in Long Lasting Insecticidal Net (LLIN)
timeFrame: at 0, 12, 24, 30, 36 months post intervention
measure: Mortality in Anopheles after one hour exposure to every study LLIN
timeFrame: at 0, 6, 12, 18, 24, 30, 36 months post intervention
measure: LLIN usage
timeFrame: at 6, 12, 18, 24, 30, 36 months post intervention
measure: Malaria infection prevalence in children 6 months to 14 years
timeFrame: 12 months post intervention
measure: Malaria infection prevalence in children 6 months to 14 years
timeFrame: 18 months post intervention
measure: Malaria infection prevalence in children 6 months to 14 years
timeFrame: 30 months post intervention
measure: Malaria infection prevalence in children 6 months to 14 years
timeFrame: 36 months post intervention
measure: Cost & DALYs of each type of bi-treated LLIN
timeFrame: Three years post intervention
Other outcomes:
measure: Insecticide resistance intensity in wild Anopheles population
timeFrame: Three years post intervention follow up
measure: P450 over-expression in wild Anopheles population
timeFrame: Three years post intervention follow up
measure: Frequency of Vgsc mutation in wild Anopheles population
timeFrame: Three years post intervention follow up
Locations:
city: Misungwi
country: Tanzania
facility: District Misungwi
state: Mwanza
Study officials:
affiliation: London School of Hygiene and Tropical Medicine
name: Natacha Protopopoff, Phd
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mosha JF, Kulkarni MA, Messenger LA, Rowland M, Matowo N, Pitt C, Lukole E, Taljaard M, Thickstun C, Manjurano A, Mosha FW, Kleinschmidt I, Protopopoff N. Protocol for a four parallel-arm, single-blind, cluster-randomised trial to assess the effectiveness of three types of dual active ingredient treated nets compared to pyrethroid-only long-lasting insecticidal nets to prevent malaria transmitted by pyrethroid insecticide-resistant vector mosquitoes in Tanzania. BMJ Open. 2021 Mar 8;11(3):e046664. doi: 10.1136/bmjopen-2020-046664.
citation: 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 Parasitol. 2011 Feb;27(2):91-8. doi: 10.1016/j.pt.2010.08.004. Epub 2010 Sep 16.
citation: Asidi A, N'Guessan R, Akogbeto M, Curtis C, Rowland M. Loss of household protection from use of insecticide-treated nets against pyrethroid-resistant mosquitoes, benin. Emerg Infect Dis. 2012 Jul;18(7):1101-6. doi: 10.3201/eid1807.120218.
citation: Ochomo EO, Bayoh NM, Walker ED, Abongo BO, Ombok MO, Ouma C, Githeko AK, Vulule J, Yan G, Gimnig JE. The efficacy of long-lasting nets with declining physical integrity may be compromised in areas with high levels of pyrethroid resistance. Malar J. 2013 Oct 24;12:368. doi: 10.1186/1475-2875-12-368.
citation: Mosha JF, Kulkarni MA, Lukole E, Matowo NS, Pitt C, Messenger LA, Mallya E, Jumanne M, Aziz T, Kaaya R, Shirima BA, Isaya G, Taljaard M, Martin J, Hashim R, Thickstun C, Manjurano A, Kleinschmidt I, Mosha FW, Rowland M, Protopopoff N. Effectiveness and cost-effectiveness against malaria of three types of dual-active-ingredient long-lasting insecticidal nets (LLINs) compared with pyrethroid-only LLINs in Tanzania: a four-arm, cluster-randomised trial. Lancet. 2022 Mar 26;399(10331):1227-1241. doi: 10.1016/S0140-6736(21)02499-5.
citation: Martin JL, Messenger LA, Mosha FW, Lukole E, Mosha JF, Kulkarni M, Churcher TS, Sherrard-Smith E, Manjurano A, Protopopoff N, Rowland M. Durability of three types of dual active ingredient long-lasting insecticidal net compared to a pyrethroid-only LLIN in Tanzania: methodology for a prospective cohort study nested in a cluster randomized controlled trial. Malar J. 2022 Mar 19;21(1):96. doi: 10.1186/s12936-022-04119-4.