Efficacy of Three Novel Bi-treated Long Lasting Insecticidal Nets

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Malaria, Anaemia

Intervention / Treatment
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* Other: Chlorfenapyr LLIN
* Other: pyriproxyfen LLIN
* Other: Piperonyl butoxide LLIN
* Other: Standard LLIN


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pyriproxyfen LLIN<br>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<br>* Dual active ingredient Long Lasting Insecticidal Net<br>|
| Experimental: Chlorfenapyr LLIN<br>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<br>* Dual active ingredient Long Lasting Insecticidal Net<br>|
| Experimental: Piperonyl butoxide LLIN<br>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<br>* Combination insecticide and synergist Long Lasting Insecticidal Net<br>|
| Active Comparator: Standard LLIN<br>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<br>* Standard Long Lasting Insecticidal Net with one insecticide<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Malaria, Vector Control, Long lasting Insecticidal Net