Efficacy of Three Novel Bi-treated Long Lasting Insecticidal Nets

NCT03554616 | Completed DMC

• 1 other identifier: ITDCZN11
• Study Type: interventional
• Target: 4,200
• Locations: 1 country
• Sites: 1

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.

Conditions

Malaria; Anaemia

Keywords

Malaria; Vector Control; Long lasting Insecticidal Net

Outcome Measures

Primary Outcomes (1)

• Malaria infection prevalence in children 6 months to 14 years

  Malaria prevalence will be assessed using Malaria Rapid Diagnostic test (CareStart Malaria histidine-rich protein 2 (HRP2)/plasmodium lactate dehydrogenase (pLDH) Combo, DiaSys, UK)

  24 months post intervention

Secondary Outcomes (12)

• Incidence of malaria cases in children 6 months to 10 years

  Two years post intervention follow up

• Prevalence of anaemia in children under 5 years old

  12, 18, 24, 30, 36 months post intervention

• Indoor Anopheles density

  Three years post intervention follow up

• Sporozoite rate

  Three years post intervention follow up

• Insecticide content in Long Lasting Insecticidal Net (LLIN)

  at 0, 12, 24, 30, 36 months post intervention

Other Outcomes (3)

• Insecticide resistance intensity in wild Anopheles population

  Three years post intervention follow up

• P450 over-expression in wild Anopheles population

  Three years post intervention follow up

• Frequency of Vgsc mutation in wild Anopheles population

  Three years post intervention follow up

Study Arms (4)

Pyriproxyfen LLIN

EXPERIMENTAL

Royal Guard® (Disease Control Technologies, LLC) is a Long Lasting Insecticidal Net made of polyethylene incorporating a mixture of 225 mg/m2 pyriproxyfen and 261mg/m2 alpha-cypermethrin. This LLIN will be distributed to all the households in 21 clusters on a 1 LLIN per two household residents basis.

Other: pyriproxyfen LLIN

Chlorfenapyr LLIN

EXPERIMENTAL

Interceptor® G2 (BASF corporation) is a LLIN made of polyester coated with a wash-resistant formulation of 200 mg/m2 chlorfenapyr and 100 mg/m2 alpha-cypermethrin. This LLIN will be distributed to all the households in 21 clusters on a 1 LLIN per two household residents basis.

Other: Chlorfenapyr LLIN

Piperonyl butoxide LLIN

EXPERIMENTAL

Olyset® Plus (Sumitomo Chemicals) is a LLIN combining Piperonyl butoxide (400mg/m2) and the repellent pyrethroid permethrin (800 mg/m2) incorporated into the polyethylene fibres. This LLIN will be distributed to all the households in 21 clusters on a 1 LLIN per two household residents basis.

Other: Piperonyl butoxide LLIN

Standard LLIN

ACTIVE COMPARATOR

Interceptor® (BASF Corporation) is a single pyrethroid-treated LLIN with alpha-cypermethrin (coated onto filaments) at a target dose of 200 mg/m2 of polyester fabric. This LLIN will be distributed to all the households in 21 clusters on a 1 LLIN per two household residents basis.

Other: Standard LLIN

Interventions

Chlorfenapyr LLIN OTHER

Dual active ingredient Long Lasting Insecticidal Net

Chlorfenapyr LLIN

pyriproxyfen LLIN OTHER

Dual active ingredient Long Lasting Insecticidal Net

Pyriproxyfen LLIN

Piperonyl butoxide LLIN OTHER

Combination insecticide and synergist Long Lasting Insecticidal Net

Piperonyl butoxide LLIN

Standard LLIN OTHER

Standard Long Lasting Insecticidal Net with one insecticide

Standard LLIN

Eligibility Criteria

• Age: 6 Months - 14 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead
• Kilimanjaro Christian Medical Centre, Tanzania: collaborator
• National Institute for Medical Research, Tanzania: collaborator
• University of Ottawa: collaborator

Study Sites (1)

District Misungwi

Misungwi, Mwanza Region, Tanzania

Location

Related Publications (10)

• 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.

  PMID: 34006037 BACKGROUND

• 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.

  PMID: 20843745 BACKGROUND

• 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.

  PMID: 22709930 BACKGROUND

• 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.

  PMID: 24156715 BACKGROUND

• 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.

  PMID: 35339225 RESULT

• Lukole EA, Cook J, Mosha JF, Matowo NS, Kulkarni MA, Mallya E, Aziz T, Martin J, Rowland M, Kleinschmidt I, Manjurano A, Mosha FW, Protopopoff N. Community benefits of mass distribution of three types of dual-active-ingredient long-lasting insecticidal nets against malaria prevalence in Tanzania: evidence from a 3-year cluster-randomized controlled trial. BMC Public Health. 2025 Jan 28;25(1):346. doi: 10.1186/s12889-025-21586-x.

  PMID: 39875853 DERIVED

• Lukole EA, Cook J, Mosha JF, Mallya E, Aziz T, Kulkarni MA, Matowo NS, Martin J, Rowland M, Kleinschmidt I, Manjurano A, Mosha FW, Protopopoff N. Will a lack of fabric durability be their downfall? Impact of textile durability on the efficacy of three types of dual-active-ingredient long-lasting insecticidal nets: a secondary analysis on malaria prevalence and incidence from a cluster-randomized trial in north-west Tanzania. Malar J. 2024 Jun 28;23(1):199. doi: 10.1186/s12936-024-05020-y.

  PMID: 38943155 DERIVED

• Mosha JF, Matowo NS, Kulkarni MA, Messenger LA, Lukole E, Mallya E, Aziz T, Kaaya R, Shirima BA, Isaya G, Taljaard M, Hashim R, Martin J, Manjurano A, Kleinschmidt I, Mosha FW, Rowland M, Protopopoff N. Effectiveness of long-lasting insecticidal nets with pyriproxyfen-pyrethroid, chlorfenapyr-pyrethroid, or piperonyl butoxide-pyrethroid versus pyrethroid only against malaria in Tanzania: final-year results of a four-arm, single-blind, cluster-randomised trial. Lancet Infect Dis. 2024 Jan;24(1):87-97. doi: 10.1016/S1473-3099(23)00420-6. Epub 2023 Sep 27.

  PMID: 37776879 DERIVED

• Messenger LA, Matowo NS, Cross CL, Jumanne M, Portwood NM, Martin J, Lukole E, Mallya E, Mosha JF, Kaaya R, Moshi O, Pelloquin B, Fullerton K, Manjurano A, Mosha FW, Walker T, Rowland M, Kulkarni MA, Protopopoff N. Effects of next-generation, dual-active-ingredient, long-lasting insecticidal net deployment on insecticide resistance in malaria vectors in Tanzania: an analysis of a 3-year, cluster-randomised controlled trial. Lancet Planet Health. 2023 Aug;7(8):e673-e683. doi: 10.1016/S2542-5196(23)00137-7.

  PMID: 37558348 DERIVED

• 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.

  PMID: 35305667 DERIVED

MeSH Terms

Conditions

Malaria; Anemia

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Natacha Protopopoff, Phd

  London School of Hygiene and Tropical Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2018
• First Posted: June 13, 2018
• Study Start: February 1, 2019
• Primary Completion: February 28, 2022
• Study Completion: February 1, 2023
• Last Updated: November 26, 2024

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: June 2023
• Access Criteria: Upon request

Locations

TA (1)