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| Name | Class |
|---|---|
| Kilimanjaro Christian Medical Centre, Tanzania | OTHER |
| National Institute for Medical Research, Tanzania | OTHER_GOV |
| University of Ottawa | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Chlorfenapyr LLIN | Other | Dual active ingredient Long Lasting Insecticidal Net |
| |
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| P450 over-expression in wild Anopheles population |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Natacha Protopopoff, Phd | London School of Hygiene and Tropical Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| District Misungwi | Misungwi | Mwanza Region | Tanzania |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34006037 | Background | 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. | |
| 20843745 |
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all IPD that underlie results in each publication will be shared and accessible in the LSHTM repository.
June 2023
Upon request
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| ID | Term |
|---|---|
| D008288 | Malaria |
| D000740 | Anemia |
| ID | Term |
|---|---|
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
| D000096724 | Mosquito-Borne Diseases |
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| pyriproxyfen LLIN |
| Other |
Dual active ingredient Long Lasting Insecticidal Net |
|
| Piperonyl butoxide LLIN | Other | Combination insecticide and synergist Long Lasting Insecticidal Net |
|
| Standard LLIN | Other | Standard Long Lasting Insecticidal Net with one insecticide |
|
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 |
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 |
| 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 |
| 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. |
| 22709930 | 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. |
| 24156715 | 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. |
| 35339225 | Result | 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. |
| 39875853 | Derived | 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. |
| 38943155 | 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. |
| 37776879 | 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. |
| 37558348 | 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. |
| 35305667 | 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. |
| D000079426 |
| Vector Borne Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |