Insecticide resistance assessment/planning

MICHAEL COLEMAN: Hello my name is Michael Coleman, and I work in the vector biology department at the Liverpool School of Tropical Medicine. I work with disease control programmes globally to improve vector control strategies. As you would have seen in other steps, controlling disease vectors often requires the use of insecticides. A major issue in vector control has been the development of insecticide resistance in vectors which can have a significant impact on vector control. In this step, we will look at insecticide resistance assessment and how a programme can manage the development and spread of resistance.

The four key learning outcomes are explain what insecticide resistance is, describe different approaches to measuring insecticide resistance, describe different approaches to managing insecticide resistance, and propose methods in different insecticide resistant settings. In malaria control, pyrethroids have been extensively used for indoor residual spraying and are the only class of insecticides that can be used currently on long lasting insecticide nets, which has led to widespread insecticide resistance to pyrethroids and has also led to control programme failure. The World Health Organisation and the Insecticide Resistance Action Committee have both defined resistance. Essentially, resistance refers to changes in an insect that increases its ability to withstand the effects of an insecticide.

Given the importance of effective vector control and the reliance on a limited number of insecticides, preserving susceptibility stages of disease vectors is critical to maintain control and reaching elimination targets. Today, insecticide resistance is widespread. Resistance is now reported in nearly every country with ongoing malaria transmission, and it affects all vector species and all classes of insecticide. As we have seen, insecticide resistance can result in the failure of a vector control programme and reduce the gains that have been made in combating this disease. Vector control is a key component to reducing the burden of vector borne diseases. It relies predominantly on three interventions.

Long lasting insecticide treated nets, indoor residual spraying, and larviciding, all of which utilise a limited number of insecticides. In 2012, to protect these insecticides, the World Health Organisation launched a global plan for insecticide resistance management in malaria vectors. While this plan focused on malaria, it is relevant for all disease vectors. The plan builds on five pillars of which pillar two is based on ensuring there is proper timely entomological and resistance monitoring and effective data management for the development of an insecticide resistance management plan. Understanding insecticide resistance in a country or region can be critical as can be observed in the case in 1996 when the South African malaria control programme switched from DDT to pyrethroids for indoor residual spraying.

By 2000, the number of malaria cases had increased significantly. This was due in part to Anopheles funestus previously eliminated by DDT being able to re-establish itself. On investigation, it was found at that an Anopheles funestus population was highly resistant to pyrethroid and had migrated back in from neighbouring countries. The action was to revert to DDT in 2000. There was a significant decline in cases. However, the decline in cases is also due to the improved diagnostics, treatment, and the establishment of the successful regional initiative the Lubombo spatial development initiative that improved vector control in Swaziland, now eSwatini, and Mozambique. Access to data for decision making is crucial.

In India, the successful malaria control programme using IRS with DDT had the side effect of controlling and almost eliminating visceral leishmaniasis in the 1970s. As the Indian visceral leishmaniasis elimination programme began in 2005, the Indian programme decided to utilise IRS with DDT again based on its previous success. However, the impact was not as high as expected. On further investigation, the sandfly vector, Phlebotomus argentipes, had become highly resistant to DDT, and so successful swap was made to pyrethroids, and a monitoring programme initiated. In both these examples, the programmes were able to react in a positive way to the insecticide resistance issue. However, it is better to be proactive rather than reactive to managing insecticide resistance.

The World Health Organisation recommends an establishment of a technical working group to engage with partners and stakeholders to drive the decision-making process and to generate an insecticide resistance management plan. The figure shown here is from the successful model established by the Zambia National Malaria Elimination Programme, which was to develop their insecticide resistance management plan in 2011, and exists today. This is part of the Broader Vector Control Technical Working Group. Using key data, the technical advisory group can make informed decisions on what, when, and where to deploy vector control and obtain the maximum benefit. Before a Programme can start, it needs to know what vectors are present and what vectors are transmitting the disease of interest.

A baseline survey should be undertaken to identify all key vectors, including vector behaviour and the resistance profile. If the vector of interest feeds and rests outdoors and is resistant to pyrethroids, then indoor residual spraying with pyrethroids is unlikely to have an impact. Phenotypic resistance is monitored using either WHO tube assays or CDC bottle assays. If resistance is present, then the intensity, or how strong that resistance is, can be determined. The higher the intensity of resistance suggests that the insecticide of choice will fail and not have the desired impact. As some resistance mechanisms can give cross-resistance to more than one class of insecticide, it is critical to understand the resistance mechanisms in the population and how they work.

Resistance101 is a free downloadable resource that has key learning stages that support this step, the eight videos that are available on YouTube under Resistance101. There are two main ways of determining resistance mechanisms, synergists, assays, and molecular and biochemical. Most programmes, due to resource funding, infrastructure, and capacity, struggle to obtain any of the key essential indicators here.

Simple, field-friendly tools are urgently needed. There are five insecticide resistance management strategies, and we will look at each one in turn. Rotations, combinations, mosaics, mixtures. Rotations are possibly the simplest to apply and can be particularly effective if the resistance gene has an associated fitness cost. In other words, resistance insects are at a selective disadvantage compared to the susceptible wild type. Essentially, two or more insecticides with differing target sites are rotated with each season.

Any pre-existing resistance mechanism, or any cross-resistance type mechanisms, could jeopardise this type of strategy. Combinations are where two or more intervention types are used to control the same vector. This may be insecticide-treated nets plus IRS or IRS plus larviciding. This relies on at least one strategy killing the vector. However, if resistance exists to a strategy already, then this is not effective. Where two insecticides, A and B, with independent resistance mechanisms are applied together in a mixture, as long as resistance to A and resistance to B are both rare, then we expect doubly resistant insects to be extremely rare. And almost all insect resistance to A will be killed by B and vice versa.

While mixtures in agriculture are common, only in 2018 was the first mixture for indoor residual spraying and vector control introduced. Mosaics are where spatially separated compounds are used, normally on a fine scale– this could be two IRS classes or an LLIN treated with different insecticides on different panels– with the potential that both insecticides will kill the vector. As with mixtures, as long as resistance to A and B are both rare, then we expect doubly resistant insects to be extremely rare. And almost all insects with resistance to A would be killed by B and vice versa. The synergist is a chemical that enhances the effect of the primary insecticide used by blocking the resistance mechanism.

Long-lasting insecticide nets that include chemical PBO have been shown to significantly reduce malaria infection in children in insecticide-resistant areas. For further information, please look at these references and download the free game, Resistance101.