Scale-up of the main vector control interventions, residual insecticides sprayed on walls or structures and/or impregnated in bed nets, together with prompt diagnosis and effective treatment, have led to a global reduction in malaria transmission. However, resistance in vectors to almost all classes of insecticides, particularly to the synthetic pyrethroids, is posing a challenge to the recent trend of declining malaria. Ten International Centers of Excellence for Malaria Research (ICEMR) located in the most malaria-endemic regions of the world are currently addressing insecticide resistance in the main vector populations, which not only threaten hope for elimination in malaria-endemic countries but also may lead to reversal where notable reductions in malaria have been documented. This communication illustrates the current status of insecticide resistance with a focus on the countries where activities are ongoing for 9 out of the 10 ICEMRs. Most of the primary malaria vectors in the ICEMR countries exhibit insecticide resistance, albeit of varying magnitude, and spanning all mechanisms of resistance. New alternatives to the insecticides currently available are still to be fully developed for deployment. Integrated vector management principles need to be better understood and encouraged, and viable insecticide resistance management strategies need to be developed and implemented.

The Program for Resistance, Immunology, Surveillance, and Modeling of Malaria (PRISM) has been conducting malaria research in Uganda since 2010 to improve the understanding of the disease and measure the impact of population-level control interventions in the country. Here, we will summarize key research findings from a series of studies addressing routine health facility-based surveillance, comprehensive cohort studies, studies of the molecular epidemiology, and transmission of malaria, evaluation of antimalarial drug efficacy, and resistance across the country, and assessments of insecticide resistance. Among our key findings are the following. First, we found that in historically high transmission areas of Uganda, a combination of universal distribution of long-lasting insecticidal-treated nets (LLINs) and sustained indoor residual spraying (IRS) of insecticides lowered the malaria burden greatly, but marked resurgences occurred if IRS was discontinued. Second, submicroscopic infections are common and key drivers of malaria transmission, especially in school-age children (5-15 years). Third, markers of drug resistance have changed over time, with new concerning emergence of markers predicting resistance to artemisinin antimalarials. Fourth, insecticide resistance monitoring has demonstrated high levels of resistance to pyrethroids, appreciable impact of the synergist piperonyl butoxide to pyrethroid susceptibility, emerging resistance to carbamates, and complete susceptibility of malaria vectors to organophosphates, which could have important implications for vector control interventions. Overall, PRISM has yielded a wealth of information informing researchers and policy-makers on the malaria burden and opportunities for improved malaria control and eventual elimination in Uganda. Continued studies concerning all the types of surveillance discussed above are ongoing.