Today is World Mosquito Day. On this day in 1897, Sir Ronald Ross discovered that Anopheles mosquitoes were responsible for the transmission of the malaria parasite. Ross’s discovery revolutionized our understanding of how to prevent malaria. Steps could be taken to target the mosquito vector to control the disease. One hundred and twenty-four years later, mosquito vector control remains a mainstay of malaria prevention. It has been estimated that between 2000 and 2015, 450 million clinical cases of malaria were averted by the widespread distribution of insecticide-treated bed nets.

Until 2019, all insecticide-treated bed nets distributed throughout Africa were treated with only one class of insecticide, pyrethroids, contributing to increasing levels of pyrethroid resistance in mosquito populations. Increases in pyrethroid resistance threaten the gains that have been made against malaria since higher levels of resistance may reduce the ability of pyrethroid-based bed nets to protect people from infectious mosquito bites.

The IVCC led New Nets Project (NNP), established in 2018 with co-funding from Unitaid and the Global Fund and complementary funding provided by the Bill & Melinda Gates Foundation and USAID, works with the next generation of nets, which are dual-insecticide nets, containing both a pyrethroid and a second insecticide. BASF’s Interceptor® G2 nets contain a pyrethroid and chlorfenapyr, and DCT’s Royal Guard® nets contain a pyrethroid plus pyriproxyfen. NNP was established with the goal of making the latest resistance-breaking net technology more widely available and affordable to malaria programmes throughout Africa by managing the pilot deployment of nets with reduced pricing via a co-payment mechanism and volume guarantee provided to BASF by MedAccess, while also establishing the evidence needed to support a policy decision by the World Health Organization (WHO) to recommend dual-insecticide nets over standard pyrethroid nets.

Although there is entomological data available showing increased mosquito mortality in hut studies for the Interceptor® G2 net and reduced mosquito fecundity for the Royal Guard® net compared to a standard pyrethroid net, two randomized control trials providing epidemiological data are required by the WHO prior to issuing a recommendation. We eagerly anticipate results from one such study in Tanzania (funded by Wellcome Trust) that will be available later this year, as well as results from a study in Benin as part of the New Nets Project that will be available in 2022. Both studies are being led by the London School of Hygiene and Tropical Medicine.

Over 20 million Interceptor® G2 and 1.5 million Royal Guard® nets have been distributed through NNP in 8 countries since 2019. By the end of the project in 2022, over 35 million Interceptor® G2 nets will have been distributed, data from the two randomized control trials will be available, and five observational studies will have collected entomological, anthropological, incidence, prevalence, net durability, and cost-effectiveness data to support impact modelling and country deployment decisions.

NNP will not only result in accelerated access to new nets but will also establish critical guidance to countries looking for the best value for money in controlling malaria. NNP is currently over one year ahead of schedule in reaching the Interceptor® G2 volume guarantee and associated price reductions. This has helped to lay the foundation for the Global Fund’s Net Transition Initiative that will help partner countries access additional new nets for the same price as standard pyrethroid nets and conduct additional research pending WHO’s review of the data and subsequent decision on their policy recommendation.

The development and deployment of dual-insecticide nets throughout Africa continue our fight against the mosquito vector of malaria first recognized by Sir Ronald Ross. Today, on World Mosquito Day, let us reflect on his seminal discovery and all the advances we have made since in combatting malaria, while also recommitting ourselves to eliminating this mosquito-borne disease.

IVCC has the pleasure of announcing that, following a meeting of the South African National Accreditation System (SANAS) Approval Committee in June 2021, the Ifakara Health Institute’s (IHI) trials facility, headquartered in Bagamoyo, Tanzania, has been granted Good Laboratory Practice (GLP) certification. This facility is internationally recognised for its expertise in testing new vector control products for industry, product development partnerships, and generates data for regulatory submissions, including WHO Prequalification evaluations.

Since 2016, IVCC has been supporting the IHI trials facility towards GLP certification with funding from the Bill & Melinda Gates Foundation. Support was provided for the GLP certification process and to make the essential infrastructure improvements required for full GLP compliance. In addition, training was provided to key staff through participation in GLP workshops and specialist courses in quality assurance and data management systems. Ongoing mentoring was provided by the GLP project team on quality management system development, including the development of Standard Operating Procedures (SOPs) and on-site facility audits were conducted to provide information on progress of the facility towards becoming fully GLP compliant.

IVCC congratulates Sarah Moore, who leads the IHI test facility, Jason Moore (test facility manager), Emmanuel Mbuba (GLP coordinator) and all of the facility staff on this wonderful achievement.

Recent semi-field results from Project BITE under IVCC’s Indo-Pacific Initiative (IPI) have shown that forest packs containing bite prevention tools could have an impact on public health beyond just personal protection. The results come from trials that UCSF-Malaria Elimination Initiative, IVCC’s lead partner on BITE, conducted at AFRIMS (Armed Forces Research Institute of Medical Sciences) and Kasetsart University in Thailand.

Project BITE aims to evaluate the effectiveness of forest packs containing a spatial emanator, topical repellent and insecticide-treated clothing when deployed to forest dwellers, goers and rangers in the Greater Mekong Subregion. The project comprises semi-field trials in Thailand and field trials in Cambodia. The trials conducted at the two sites in Thailand measured the protective efficacy of the products using the following endpoints: landing inhibition, knockdown, delayed mortality at 24 hours and blood feeding inhibition.

The semi-field findings demonstrated that these products not only prevent mosquitoes from landing but can also kill or delay them from seeking another host, thus preventing diversion of mosquitoes to nearby non-users of the tools. Delaying host-seeking and feeding inhibition also could have an additional impact on vectorial capacity by reducing human biting rate (HBR) and the vectors’ lifetime reproductive output.

Following the semi-field trials, a formative assessment is now underway in Mondulkiri province in Cambodia, looking at user acceptability of the products. A field entomology trial will take place in Q3-Q4 2021, and a field epidemiological trial will commence in Q1 2022, both at the same sites in Mondulkiri, which will test the hypotheses coming out of the semi-field results.

IVCC and its partners are hopeful that the evidence generated by BITE will help make the case to national programmes and donors on the effectiveness of forest packs in the fight against outdoor malaria transmission amongst at-risk groups – both in Asia-Pacific and beyond.

The global push to expand coverage of current vector control tools, namely long-lasting insecticidal nets (LLIN’s) and indoor residual spraying (IRS), has led to a halving of the malaria burden across sub-Saharan Africa between 2000 and 2015. This major headway has resulted in a renewed interest in the elimination of the disease. However, the recent stagnation in progress observed between 2015 and 2018 suggests that additional strategies, unaffected by contemporary control challenges including inseciticide resistance, are urgently needed to supplement existing interventions and bridge the gap between control and elimination.

The potential contribution of house-based interventions to malaria control and elimination has been emphasised in the RBM Partnership to End Malaria (RBM) ‘Global Framework for Action and Investment to Defeat Malaria 2016-2030 (AIM)’. This form of vector control, which involves the blocking of mosquito entry routes contributed to malaria elimination in other countries in the early decades of the 1900s but remains largely underexploited in Africa. However, the rapid economic growth in Africa and the need for additional houses to meet its expanding population offer an unrivalled opportunity to deploy improved housing as a complementary measure to existing malaria control tools. Data from observational studies, systematic review and meta-analysis of data collected in a range of African countries during Demographic and Health Surveys and Malaria Indicator Surveys suggest that residents of houses with features that restrict mosquito entry, for example closed eave and screened window, had lower rates  of malaria infection.

Standard house improvements do not generally rely on the use of insecticides to reduce malaria transmission. Nonetheless, a wide array of house modification strategies including In2Care® EaveTubes, insecticide-treated eave baffles and insecticide-treated eave and window screening, have an insecticidal component which, according to modelling simulation, could contribute to a community-wide effect under high coverage scenarios. This form of house improvement has recently been classified by the WHO Vector Control Advisory Group (VCAG) as “Lethal House Lure” vector control strategy. The first prototype of this new class of control method to generate epidemiological evidence is the In2Care® EaveTubes intervention. This innovative control method consists of installing plastic piping fitted with insecticide-treated inserts into house walls at eave height. Human odours emanating from houses are then channelled through the tubes attracting Anopheles mosquitoes, which prefer entering houses through the eaves. The static netting insert placed inside the tube is treated with an insecticide powder formulation which delivers a lethal dose to mosquitoes that make contact with it.

The effectiveness of In2Care® EaveTubes, combined with general house improvement (screening of windows and patching of holes in walls) has recently been investigated in a cluster randomized controlled trial in a high malaria transmission area with pyrethroid resistant mosquito populations in central Cote d’Ivoire. Findings from this village-level trial showed that children living in improved houses fitted with EaveTubes and house screening were ~40% less likely to contract malaria compared to those living in villages where the intervention was not installed. The impact of the technology was greater where village-level coverage was higher. The technology reduced indoor vector populations by approximately 60% in comparison to control villages and was shown to be similarly cost-effective to other available malaria control tools. The high impact of the EaveTubes and house screening reported in this trial confirm the potential contribution of house-based control method towards malaria elimination.

Another randomised controlled trial demonstrating efficacy of the EaveTubes intervention in a different geographical setting is required before WHO policy can be issued. However, the path to market for house-based interventions for malaria control is challenging and  will require cross sectoral collaboration, particularly with the housing sector, to promote incorporation of protective designs into housing in areas at risk of malaria.