By Mark Rowland
Long term research by LSHTM on long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) of houses have contributed substantially to the reductions in malaria burden attributable to vector control over the last 20 years. However increasing insecticide resistance threatens progress, and LSHTM researchers are actively engaged in research to counter this threat - conducting trials to evaluate new resistance-breaking products and exploring alternative methods of vector control.
Recognising the threat that resistance presented to the future of pyrethroid LLIN and the long lead time required to develop safe and effective alternatives, Malaria Centre researchers with in strategic partnership with WHO and pesticide manufacturers to identify and test new active ingredients for nets and IRS. As early as 2008 a new type of LLIN, the PBO-pyrethroid LLIN, which contained a chemical synergist to neutralise metabolic resistance, had demonstrated the entomological potential of PBO synergist LLIN over pyrethroid-only LLIN, in experimental hut studies. Uptake of PBO-LLIN by malaria control agencies remained slow due to the extra cost entailed and the absence of definitive evidence that pyrethroid resistance was an obstacle to control.
In some countries standard LLIN have remained partially protective, as demonstrated in a multi-country study which investigated whether insecticide resistance was associated with loss of effectiveness of LLIN and increased malaria burden. No evidence was found for an association between insecticide resistance and infection prevalence. Child users of nets, although better protected than non-users, were nevertheless subject to high malaria infection risk especially in Africa.
In order to demonstrate the added benefit and protection of PBOpyrethroid LLIN, more rigorous evidence was sought. The cluster randomised trial (CRT) conducted in NW Tanzania demonstrated that PBO - LLIN would reduce malaria infection prevalence by 44% compared to standard pyrethroid LLIN for over two years. This coincided with the new WHO policy requiring RCT evidence for improved malaria control impact before recommending any new class of vector control product. Armed with the new evidence, WHO in 2017 recommended PBO-pyrethroid LLIN as a new product class to control malaria transmitted by pyrethroid resistant vectors. The Global Fund and President’s Malaria Initiative responded by placing significant country orders for PBO LLIN in 2018. A second CRT of two types of PBO LLIN and two standard LLIN was initiated in Uganda on a larger scale in over a hundred sub-districts. It is due to report at the end of 2019.
Dual AI LLIN combining mixtures of insecticide with a differing modes of action developed through the LSHTM/PAMVERC/IVCC alliance have completed Phase 1 laboratory and 2 experimental hut trials and are now ready for community-scale CRT evaluation. The trial in Tanzania is comparing the LLIN that combines pyrethroid and chlorfenapyr with a LLIN that combines pyrethroid and pyriproxifen and a PBO-LLIN. A parallel CRT has started in Benin. Two CRTs are required to generate the evidence for the full WHO recommendation. These Dual AI LLIN will form the next generation of LLIN to continue malaria control progress.
House improvements for malaria control has been another major movement. Eave tubes are a novel vector control tool which aims to prevent malaria by bringing insecticide resistant mosquitoes into contact with a high dose of insecticide as they try to enter though screened ports fixed in the house walls. A CRT is currently taking place in central Cote d’Ivoire. Other studies have investigated the use of insecticide treated wall linings, an alternative to IRS, designed to make interiors more aesthetic while providing a longlasting substrate for insecticide. Improved housing should improve malaria prevention.
A study which analysed national survey data from 21 countries found that modern housing, built with metal or tiled roofs and concrete or brick walls, was associated with up to 14% reduction in the odds of malaria infection in children compared to more traditional housing. The effect of ITNs was additive; among the same children, the odds of malaria infection were 15% lower among ITN users than non-users.
The Building out Vector-Borne Diseases (BOVA) network is focused on control of malaria and other vector-borne diseases by improving the built environment in sub-Saharan Africa. It is providing small-scale funding for relevant research among African scientists. A cohort study in rural Uganda, in relation to a mass scale-up of control efforts, found a rapid increase in the prevalence of modern housing between 2011-17. Implementation of IRS led to declines in malaria transmission, and housing changes were associated with additional reductions in mosquito density and parasite prevalence.
A CRT in neighbouring Tanzania also found that a single application of IRS using long-lasting Actellic CS (pirimiphos methyl) would reduce the prevalence of malaria for over one year. LSHTM has generated a wealth of entomological information on IRS and is working with modellers from Imperial College to examine whether this will judge IRS effectiveness in countries other than the location of the CRTs that generated the initial evidence. A modelling approach is also being taken to examine the conditions whereby the application of systemic insecticides to domestic cattle will control malaria transmitted by partially zoophilic vectors. Interactions between mosquito biting behaviours and relative availabilities of alternative blood-host species are important to success. The outcomes indicate this systemic treatments will complement distributions of LLINs.
In order to achieve malaria elimination, it will be necessary to compliment indoor interventions with others such as larviciding. Larviciding can be difficult to implement, in part because water bodies are often numerous and can be challenging to locate. A trial is comparing spatial intelligence system comprising satellite data and drones, combined with spatial modelling, to improve the detection of breeding sites.