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Since the start of Roll Back Malaria (RBM) in 1998 funding for malaria control has increased dramatically, resulting in the current peak of $2.5billion spent on global malaria control annually. Vector control has been a major source of expenditure, with the focus in sub-Saharan Africa being free Long-Lasting Insecticidal Net (LLIN) distribution and Indoor Residual Spraying (IRS). Use of pyrethroid insecticides in agriculture and rapid scaling up of pyrethroid LLINs and IRS for malaria vector control has led to the development and spread of pyrethroid resistance in Anopheles gambiae malaria vectors. In community use, the level of insecticide resistance at which malaria control is compromised remains uncertain, but experimental hut trials in Benin, an area of high frequency pyrethroid resistance, showed that holed pyrethroid Insecticide Treated Nets (ITNs) failed to protect sleepers from being bitten and no longer had a mass killing effect on malaria vectors. If LLINs and IRS are to remain effective it is essential that new public health insecticides are developed to address the growing problem of resistance. All insecticides that are currently recommended by the World Health Organization Pesticide Evaluation Scheme (WHOPES) for LLIN or IRS belong to just four classes of chemistry that act on nerve and muscle targets; namely pyrethroid, organophosphate (OP), carbamate, and organochlorine (DDT). The Global Plan for Insecticide Resistance Management (GPIRM) states that in areas of pyrethroid resistance or high LLIN coverage, alternative insecticide classes should be used for IRS in a rotation. Rotation of insecticides is very difficult to implement due to a lack of new public health insecticides. The Stockholm Convention on Persistent Organic Pollutants (POPs) came into effect in 2004, yet the use of DDT (classified as a POP) for malaria control has been allowed to continue under exemption since then due to a perceived absence of equally effective and efficient alternatives. Alternative classes of insecticide for IRS such as pirimiphos-methyl (OP) and bendiocarb (carbamate) have a relatively short residual duration of action (2-6 months according to WHOPES). In areas of year-round transmission, multiple spray cycles are required resulting in significantly higher costs for malaria control programs and user fatigue. For continued cost-effectiveness of IRS programs it is important to develop new longer-lasting formulations of currently available insecticides, while also developing insecticides with new modes of action. Pyrethroids are the only insecticides that are currently recommended by WHOPES for LLIN. Therefore, it is essential to develop and evaluate new insecticides for LLIN before effectiveness of pyrethroid LLIN is compromised.\ud 6\ud This thesis consisted of a sequence of tests to evaluate the efficacy of several new formulations of WHOPES recommended insecticides and novel insecticides both in the laboratory and against wild mosquitoes entering experimental huts.\ud Specifically these studies have shown that:\ud Addition of eave baffles in experimental huts succeeded in reducing the potential for mosquito escape and is preferable to the assumption of doubling veranda catch to allow for unrecorded escapes (research paper 2).\ud A Capsule Suspension (CS) formulation of pirmiphos-methyl used for IRS showed a significant improvement in terms of longevity on mud, concrete and plywood when compared with the previously recommended Emulsifiable Concentrate (EC) formulation in laboratory and experimental hut bioassays (research paper 3).\ud A new formulation of deltamethrin with polymeric binder (SC-PE) for IRS showed only a slight improvement over the existing Water Dispersible Granules (WG) formulation in bioassays, but both formulations equalled DDT in experimental huts and should provide annual mosquito control. Deltamethrin SC-PE or WG should only be considered for use by malaria control programs where there is low pyrethroid LLIN coverage (research paper 4).\ud In experimental hut trials, chlorfenapyr (pyrrole) IRS was equivalent to alphacypermethrin against pyrethroid susceptible An. arabiensis but superior against pyrethroid-resistant Cx. quinquefasciatus. The unique non-neurological mode of action shows no cross-resistance to existing resistance mechanisms and should be successful for control of pyrethroid resistant mosquitoes (research paper 5).\ud In experimental hut trials, chlorfenapyr ITNs produced relatively high mortality rates of pyrethroid susceptible An. arabiensis but due to low irritability there was only a small reduction in blood-feeding (research paper 8). Mortality rates were similar to those produced by deltamethrin ITN.\ud Unlike neurotoxic insecticides, such as pyrethroids and carbamates, chlorfenapyr owes its toxicity to the disruption of molecular pathways which enable cellular respiration to occur. Conventional 3 minute contact bioassay based on WHOPES guidelines is suitable for pyrethroids but does not predict field performance of\ud 7\ud chlorfenapyr, which is metabolic in nature and sensitive to temperature and the phase of the insect’s circadian activity rhythm (research paper 9).\ud Combining chlorfenapyr with a more excito-repellent pyrethroid on mosquito nets produced higher levels of blood-feeding inhibition than chlorfenapyr alone, in tunnel tests with both pyrethroid susceptible and resistant strains of Cx. quinquefasciatus (research paper 10).\ud Restricting insecticide to particular surfaces of the nets (top only or sides only) indicated that An. arabiensis contacts both the top and sides of a mosquito net during host-seeking behaviour. These results support the rationale behind the ‘2-in-1’ mosquito net, in which the top of the net is treated with a non-pyrethroid insecticide and the sides with pyrethroid (research paper 11). |
