Efficacy of Three Novel Bi-treated Long Lasting Insecticidal Nets

Malaria Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03554616
• Other study ID #: ITDCZN11
• Status: Completed
• Phase: N/A
• Start date: February 1, 2019
• Est. completion date: February 1, 2023

Study information

• Verified date: April 2022
• Source: London School of Hygiene and Tropical Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4200
• Est. completion date: February 1, 2023
• Est. primary completion date: February 28, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Months to 14 Years

Eligibility

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

Related Conditions & MeSH terms

• Anaemia
• Malaria

Intervention

Other:
• Chlorfenapyr LLIN
Dual active ingredient Long Lasting Insecticidal Net
• pyriproxyfen LLIN
Dual active ingredient Long Lasting Insecticidal Net
• Piperonyl butoxide LLIN
Combination insecticide and synergist Long Lasting Insecticidal Net
• Standard LLIN
Standard Long Lasting Insecticidal Net with one insecticide

Locations

Country	Name	City	State
Tanzania	District Misungwi	Misungwi	Mwanza

Sponsors (4)

Lead Sponsor	Collaborator
London School of Hygiene and Tropical Medicine	Kilimanjaro Christian Medical Centre, Tanzania, National Institute for Medical Research, Tanzania, University of Ottawa

Country where clinical trial is conducted

Tanzania, 

References & Publications (8)

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. — View 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 co — View 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 — View Citation

N'Guessan R, Odjo A, Ngufor C, Malone D, Rowland M. A Chlorfenapyr Mixture Net Interceptor(R) G2 Shows High Efficacy and Wash Durability against Resistant Mosquitoes in West Africa. PLoS One. 2016 Nov 16;11(11):e0165925. doi: 10.1371/journal.pone.0165925. eCollection 2016. — View Citation

Ngufor C, N'Guessan R, Fagbohoun J, Todjinou D, Odjo A, Malone D, Ismail H, Akogbeto M, Rowland M. Efficacy of the Olyset Duo net against insecticide-resistant mosquito vectors of malaria. Sci Transl Med. 2016 Sep 14;8(356):356ra121. doi: 10.1126/scitranslmed.aad3270. — View 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. — View Citation

Protopopoff N, Mosha JF, Lukole E, Charlwood JD, Wright A, Mwalimu CD, Manjurano A, Mosha FW, Kisinza W, Kleinschmidt I, Rowland M. Effectiveness of a long-lasting piperonyl butoxide-treated insecticidal net and indoor residual spray interventions, separately and together, against malaria transmitted by pyrethroid-resistant mosquitoes: a cluster, randomised controlled, two-by-two factorial design trial. Lancet. 2018 Apr 21;391(10130):1577-1588. doi: 10.1016/S0140-6736(18)30427-6. Epub 2018 Apr 11. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Insecticide resistance intensity in wild Anopheles population	Twice a year insecticide resistance will be assessed in wild Anopheles. 24 hours mortality will be recorded in Anopheles exposed to different concentrations of insecticides in CDC bottle assay or WHO test	Three years post intervention follow up
Other	P450 over-expression in wild Anopheles population	P450 genes involved in pyrethroid insecticide resistance will be monitored in the 4 arms once a year using reverse-transcription quantitative polymerase chain reaction (PCR)	Three years post intervention follow up
Other	Frequency of Vgsc mutation in wild Anopheles population	A sub sample of mosquitoes collected in the 4 arms will be tested for the Vgsc mutation involved in pyrethroid resistance using Taq Man PCR.	Three years post intervention follow up
Primary	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	Incidence of malaria cases in children 6 months to 10 years	Malaria incidence cases will be assessed using Malaria Rapid Diagnostic test (CareStart)	Two years post intervention follow up
Secondary	Prevalence of anaemia in children under 5 years old	Hemoglobin (Hb) concentration will be tested to assess anaemia (<8 g/dL) using HemoCue Hb 201+.	12, 18, 24, 30, 36 months post intervention
Secondary	Indoor Anopheles density	Anopheles density per house per night will be assess every quarter in 8 houses per cluster using light trap. Anopheles density and sporozoite rate will be used to estimate the entomological inoculation rate (EIR)	Three years post intervention follow up
Secondary	Sporozoite rate	A sub-samples of Anopheles collected indoor will be tested for Plasmodium falciparum circumsporozoite protein using an ELISA test. Sporozoite rate will be used to estimate the EIR with Anopheles density.	Three years post intervention follow up
Secondary	Insecticide content in Long Lasting Insecticidal Net (LLIN)	30 LLINs will be collected at yearly interval and Insecticide content in g/kg assessed with High-performance liquid chromatography (HPLC)	at 0, 12, 24, 30, 36 months post intervention
Secondary	Mortality in Anopheles after one hour exposure to every study LLIN	30 LLINs will be sampled every 6 months and tested in cone bio assay or tunnel test using resistant Anopheles and susceptible Kisumu Anopheles to assess for bio efficacy. 24, 48 and 72 hours mortality post exposure will be recorded.	at 0, 6, 12, 18, 24, 30, 36 months post intervention
Secondary	LLIN usage	The proportion of study participant declaring sleeping under a LLIN the previous night will be assessed during household survey every 6 months using a questionnaire.	at 6, 12, 18, 24, 30, 36 months post intervention
Secondary	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)	12 months post intervention
Secondary	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)	18 months post intervention
Secondary	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)	30 months post intervention
Secondary	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)	36 months post intervention
Secondary	Cost & DALYs of each type of bi-treated LLIN	Cost of each intervention will be gathered and used to calculate cost per malaria case averted and cost per DALY averted	Three years post intervention

External Links

•   WHO, Conditions for deployment of mosquito nets treated with a pyrethroid and piperonyl butoxide, G.M. Programme, Editor. 2017, World Health Organization: Geneva.