Differential impact of dual-active ingredient long-lasting insecticidal nets on primary malaria vectors: a secondary analysis of a 3-year, single-blind, cluster-randomised controlled trial in rural Tanzania

Matowo, Nancy S.; Kulkarni, Manisha A.; Messenger, Louisa A.; Jumanne, Mohamed; Martin, Jackline; Mallya, Elizabeth; Lukole, Eliud; Mosha, Jacklin F; Moshi, Oliva; Shirima, Boniface; Kaaya, Robert; Rowland, Mark; Manjurano, Alphaxard; Mosha, Franklin W.; Protopopoff, Natacha

doi:10.1016/s2542-5196(23)00048-7

Cited by 13 publications

(11 citation statements)

References 33 publications

(62 reference statements)

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“…For population modification approaches, in addition to components required for homing, the gene drive system could likely also encode genes designed to reduce or prevent parasite transmission [ 148 ], so that the intended impact on vectorial capacity is to reduce the vector competence of target populations for Plasmodium . As the gene drive system increases in frequency and spreads in target populations, either the sporozoite rate, or the potential for parasite infection in field assays, could be compared in field-caught females with and without the gene drive system [ 36 – 38 , 70 , 74 , 81 , 149 , 150 ]. Genetic efficacy assessment would also include monitoring for stability of the gene drive system including in the case of population modification for the potential of the functional effector gene to become uncoupled from the homing mechanism.…”

Section: Assessing Genetic Efficacy In Phase 2amentioning

confidence: 99%

“…For population suppression gene drive, comparison of the density of target populations of mosquitoes at release and control locations will be an important entomological parameter to assess [ 70 , 71 , 74 , 75 , 81 , 90 , 151 ]. For example, a battery of ovitraps and BG sentinel traps covering both control and release locations were used to ascertain measurements relating to adult mosquito density in a trial of GMMs to control Aedes aegypti in Brazil [ 114 ].…”

Section: Assessing Entomological Efficacy In Phase 2bmentioning

confidence: 99%

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Considerations for first field trials of low-threshold gene drive for malaria vector control

Connolly,

Burt,

Christophides

et al. 2024

Malar J

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Sustainable reductions in African malaria transmission require innovative tools for mosquito control. One proposal involves the use of low-threshold gene drive in Anopheles vector species, where a ‘causal pathway’ would be initiated by (i) the release of a gene drive system in target mosquito vector species, leading to (ii) its transmission to subsequent generations, (iii) its increase in frequency and spread in target mosquito populations, (iv) its simultaneous propagation of a linked genetic trait aimed at reducing vectorial capacity for Plasmodium, and (v) reduced vectorial capacity for parasites in target mosquito populations as the gene drive system reaches fixation in target mosquito populations, causing (vi) decreased malaria incidence and prevalence. Here the scope, objectives, trial design elements, and approaches to monitoring for initial field releases of such gene dive systems are considered, informed by the successful implementation of field trials of biological control agents, as well as other vector control tools, including insecticides, Wolbachia, larvicides, and attractive-toxic sugar bait systems. Specific research questions to be addressed in initial gene drive field trials are identified, and adaptive trial design is explored as a potentially constructive and flexible approach to facilitate testing of the causal pathway. A fundamental question for decision-makers for the first field trials will be whether there should be a selective focus on earlier points of the pathway, such as genetic efficacy via measurement of the increase in frequency and spread of the gene drive system in target populations, or on wider interrogation of the entire pathway including entomological and epidemiological efficacy. How and when epidemiological efficacy will eventually be assessed will be an essential consideration before decisions on any field trial protocols are finalized and implemented, regardless of whether initial field trials focus exclusively on the measurement of genetic efficacy, or on broader aspects of the causal pathway. Statistical and modelling tools are currently under active development and will inform such decisions on initial trial design, locations, and endpoints. Collectively, the considerations here advance the realization of developer ambitions for the first field trials of low-threshold gene drive for malaria vector control within the next 5 years.

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Section: Assessing Genetic Efficacy In Phase 2amentioning

confidence: 99%

Section: Assessing Entomological Efficacy In Phase 2bmentioning

confidence: 99%

Considerations for first field trials of low-threshold gene drive for malaria vector control

Connolly,

Burt,

Christophides

et al. 2024

Malar J

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“…This may be due to an increase in the proportion of zoophilic An. arabiensis recorded resting in the huts, (31).…”

Section: Discussionmentioning

confidence: 99%

“…An.arabiensis was the predominant species in the EHT when the 24 and 36 months nets were tested. Matowo et al (31) have reported that Interceptor ® G2 was less effective against exophilic (An. arabiensis) mosquitoes.…”

Section: Discussionmentioning

confidence: 99%

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Bio-efficacy of field aged novel class of long-lasting insecticidal nets, against pyrethroid-resistant malaria vectors in Tanzania: A series of experimental hut trials

Martin,

Messenger,

Rowland

et al. 2023

Preprint

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New classes of long-lasting insecticidal nets (LLINs) incorporating two insecticides, or an insecticide and a synergist, are recommended by the World Health Organization (WHO) to prevent malaria transmitted by mosquito vectors resistant to pyrethroid and other common insecticide classes. This study was nested in a large-scale cluster-randomized controlled trial conducted in Tanzania. A series of experimental hut trials (EHTs). The following field collected LLINs were assessed: 1/OlysetTM Plus (combining piperonyl butoxide synergist and permethrin), 2/Interceptor® G2 (chlorfenapyr and alpha-cypermethrin), 3/Royal Guard® (pyriproxyfen and alpha-cypermethrin), 4/Interceptor® (alpha-cypermethrin only), 5/a new Interceptor®, and 6/an untreated net. Thirty nets of each type were withdrawn from the community at 12, 24 and 36 months after distribution and used for the EHTs. Pre-specified outcomes were 72-hour mortality for Interceptor® G2, 24-hour mortality for OlysetTM Plus, and fertility based on egg development stage for Royal Guard®. Overall; Interceptor® G2 LLINs induced higher 72-hour mortality compared to standard LLINs of the same age up to 12 months (44% vs 21%), OR: 3.5, 95% CI: 1.9 – 6.6, p-value < 0.001 and 24-hour mortality was only significantly higher in OlysetTM Plus when new (OR: 13.6, 95%CI: 4.4 – 41.3, p-value < 0.001) compared to standard LLINs but not at 12 months (17% vs 13%; OR: 2.1, 95% CI: 1.0 – 4.3; p-value = 0.112). A small non-significant effect of pyriproxyfen on Anopheles fertility was observed for Royal Guard® up to 12 months (75% vs 98%, OR: 1.1, 95% CI: 0.0 – 24.9, p-value = 0.951). There was no evidence of a difference in the main outcomes for any of the new class of LLINs at 24 and 36 months compared to standard LLINs. Interceptor® G2 LLINs showed superior bio-efficacy compared to standard LLINs for only up to 12 months and the effect of OlysetTM Plus was observed when new for all species and 12 months for An. gambiae s.l. only. The pyriproxyfen component of Royal Guard® had a short and limited effect on fertility

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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

Mosha,

Matowo,

Kulkarni

et al. 2024

The Lancet Infectious Diseases

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Differential impact of dual-active ingredient long-lasting insecticidal nets on primary malaria vectors: a secondary analysis of a 3-year, single-blind, cluster-randomised controlled trial in rural Tanzania

Cited by 13 publications

References 33 publications

Considerations for first field trials of low-threshold gene drive for malaria vector control

Considerations for first field trials of low-threshold gene drive for malaria vector control

Bio-efficacy of field aged novel class of long-lasting insecticidal nets, against pyrethroid-resistant malaria vectors in Tanzania: A series of experimental hut trials

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

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