Central America is a unique geographical region that connects North and South America, enclosed by the Caribbean Sea to the East, and the Pacific Ocean to the West. This region, encompassing Belize, Costa Rica, Guatemala, El Salvador, Honduras, Panama, and Nicaragua, is highly vulnerable to the emergence or resurgence of mosquito-borne and tick-borne diseases due to a combination of key ecological and socioeconomic determinants acting together, often in a synergistic fashion. Of particular interest are the effects of land use changes, such as deforestation-driven urbanization and forest degradation, on the incidence and prevalence of these diseases, which are not well understood. In recent years, parts of Central America have experienced social and economic improvements; however, the region still faces major challenges in developing effective strategies and significant investments in public health infrastructure to prevent and control these diseases. In this article, we review the current knowledge and potential impacts of deforestation, urbanization, and other land use changes on mosquito-borne and tick-borne disease transmission in Central America and how these anthropogenic drivers could affect the risk for disease emergence and resurgence in the region. These issues are addressed in the context of other interconnected environmental and social challenges.

New vector control paradigms expanding the use of spatial repellents are promising, but there are many gaps in our knowledge about how repellents work and how their long-term use might affect vector populations over time. Reported here are findings from a series of in vitro studies that investigated the plasticity and heritability of spatial repellent (SR) behaviors in Aedes aegypti exposed to airborne transfluthrin, including results that indicate a possible link between repellent insensitivity and insecticide resistance. A dual-choice chamber system was used to observe directional flight behaviors in Aedes aegypti mosquitoes exposed to passively emanating transfluthrin vapors (1.35 mg/m³). Individual SR responder and SR non-responder mosquitoes were identified, collected and maintained separately according to their observed phenotype. Subsequent testing included re-evaluation of behavioral responses in some mosquito cohorts as well as testing the progeny of selectively bred responder and non-responder mosquito strains through nine generations. At baseline (F₀ generation), transfluthrin actively repelled mosquitoes in the assay system. F₀ mosquitoes repelled upon initial exposure to transfluthrin vapors were no more likely to be repelled again by subsequent exposure 24h later, but repelled mosquitoes allowed to rest for 48h were subsequently repelled at a higher proportion than was observed at baseline. Selective breeding of SR responders for nine generations did not change the proportion of mosquitoes repelled in any generation. However, selective breeding of SR non-responders did produce, after four generations, a strain of mosquitoes that was insensitive to the SR activity of transfluthrin. Compared to the SR responder strain, the SR insensitive strain also demonstrated decreased susceptibility to transfluthrin toxicity in CDC bottle bioassays and a higher frequency of the V1016I^kdr mutation. SR responses to volatile transfluthrin are complex behaviors with multiple determinants in Ae. aegypti. Results indicate a role for neurotoxic irritation of mosquitoes by sub-lethal doses of airborne chemical as a mechanism by which transfluthrin can produce SR behaviors in mosquitoes. Accordingly, how prolonged exposure to sub-lethal doses of volatile pyrethroids might impact insecticide resistance in natural vector populations, and how already resistant populations might respond to a given repellent in the field, are important considerations that warrant further monitoring and study. Results also highlight the critical need to develop new repellent active ingredients with novel mechanisms of action. There is growing evidence to support the expanded use of spatial repellents for vector control, but there are still many uncertainties about how repellents work and how their long term use may impact vector populations over time. Here, we conducted a series of in vitro experiments that investigated spatial repellent (SR) behaviors in Aedes aegypti mosquitoes exposed to airborne transfluthrin, a volatile pyrethroid commonly used in repellent products. We were able to show that repellent insensitivity is linked to reduced insecticide susceptibility and increased knock down resistance allele frequency, indicating that sub-lethal doses of airborne transfluthrin can elicit SR behaviors in mosquitoes by inducing an agitated state via neurotoxic pathways independent of olfactory stimulation. This raises questions about how the use of volatile pyrethroid repellents may impact insecticide resistance in target vectors over time, highlighting the need to further understand all of the physiological drivers of SR behaviors and emphasizing the requirement to develop new repellent active ingredients with novel, non-toxic mechanisms of action.

The cause of malaria transmission has been known for over a century but it is still unclear whether entomological measures are sufficiently reliable to inform policy decisions in human health. Decision-making on the effectiveness of new insecticide-treated nets (ITNs) and the indoor residual spraying of insecticide (IRS) have been based on epidemiological data, typically collected in cluster-randomised control trials. The number of these trials that can be conducted is limited. Here we use a systematic review to highlight that efficacy estimates of the same intervention may vary substantially between trials. Analyses indicate that mosquito data collected in experimental hut trials can be used to parameterize mechanistic models for Plasmodium falciparum malaria and reliably predict the epidemiological efficacy of quick-acting, neuro-acting ITNs and IRS. Results suggest that for certain types of ITNs and IRS using this framework instead of clinical endpoints could support policy and expedite the widespread use of novel technologies.

Background: Ghana has been implementing the indoor residual spraying (IRS) of insecticides since 2006, focusing operations in the north. Insecticide resistance concerns prompted a switch from pyrethroids to organophosphates, beginning gradually in 2011 and switching fully to the micro-encapsulated formulation of pirimiphosmethyl (PM CS), Actellic^® 300CS, a third-generation indoor residual spraying (3GIRS) product, by 2014. Entomological surveillance studies have shown IRS to be a highly effective malaria control tool, but epidemiological evidence is needed as well. Countrywide prevalence surveys have shown that malaria parasite prevalence in children under 5 years of age in Northern, Upper East, and Upper West Regions had declined to less than 40% in each region by 2016. Similarly, malaria deaths in children under 5 years of age have also been declining nationally since 2009. Although IRS is suspected to have contributed to this decline, stronger evidence is needed to link the IRS interventions to the epidemiological impact. Methods: To assess the epidemiological impact of Ghana’s IRS programmatic activities, a retrospective, observational analysis using routine epidemiological data was conducted to compare malaria incidence rates from IRS and non-IRS districts in Northern, Upper East, and Upper West Regions. Routine epidemiological data consisted of passive malaria case surveillance data reported in the District Health Information System 2 (DHIS2); with cases representing patients with suspected malaria who had sought care in the public health system and had received a confirmatory diagnosis with a positive malaria RDT result. Final routine data were extracted in September 2018. All districts that had received IRS were included in the analysis and compared to all non-IRS districts within the same region. In the Northern Region, only PMI districts were included in the analysis, as they had similar historical data. Results: District-level analysis from Northern Region from 2015 to 2017 of the aggregate malaria incidence reported from IRS districts relative to non-IRS comparator districts showed 39%, 26%, and 58% fewer confirmed malaria cases reported from IRS districts in 2015, 2016, and 2017, respectively. This translates to approximately 257,000 fewer cases than expected over the three years. In Upper East Region, the effect on reported malaria cases of withdrawing IRS from the region was striking; after spray operations were suspended in 2015, incidence increased an average of 485% per district (95% confidence interval: 330% to 640%) compared to 2014. Conclusions: The current observational analysis results are in line with the entomological studies in demonstrating the positive contribution of IRS with a 3GIRS product to malaria control programmes in northern Ghana and the value of using routine surveillance and implementation data to rapidly assess the impact of vector control interventions in operational settings, even in complex implementation environments.

Campaigns for the continued reduction and eventual elimination of malaria may benefit from new and innovative vector control tools. One novel approach being considered uses a push-pull strategy, whereby spatial repellents are used in combination with outdoor baited traps. The desired effect is the behavioural manipulation of mosquito populations to elicit movement of vectors away from people and into traps. Here, a prototype push-pull intervention was evaluated using an experimental hut methodology to test proof-of-principle for the strategy against two natural vector populations, Anopheles albimanus and Anopheles vestitipennis, in Belize, Central America. A Latin square study design was used to compare mosquito entry into experimental huts and outdoor traps across four different experimental conditions: 1) control, with no interventions; 2) pull, utilizing only outdoor traps; 3) push, utilizing only an indoor spatial repellent; and 4) push-pull, utilizing both interventions simultaneously. For An. vestitipennis, the combined use of an indoor repellent and outdoor baited traps reduced average nightly mosquito hut entry by 39% (95% CI: [0.37 – 0.41]) as compared to control and simultaneously increased the nightly average densities of An. vestitipennis captured in outdoor baited traps by 48% (95% CI: [0.22 – 0.74]), compared to when no repellent was used. Against An. albimanus, the combined push-pull treatment similarly reduced hut entry, by 54% (95% CI: [0.40 – 0.68]) as compared to control; however, the presence of a repellent indoors did not affect overall outdoor trap catch densities for this species. Against both anopheline species, the combined intervention did not further reduce mosquito hut entry compared to the use of repellent alone. The prototype intervention evaluated here clearly demonstrated that push-pull strategies have potential to reduce human-vector interactions inside homes by reducing mosquito entry, and highlighted the possibility for the strategy to simultaneously decrease human-vector interactions outside of homes by increasing baited trap collections. However, the variation in effect on different vectors demonstrates the need to characterize the underlying behavioral ecology of target mosquitoes in order to drive local optimization of the intervention.

Ségou Region in Central Mali is an area of high malaria burden with seasonal transmission, high access to and use of long-lasting insecticidal nets (LLINs), and resistance to pyrethroids and DDT well documented in Anopheles gambiae s.l. (the principal vector of malaria in Mali). Ségou has recently received indoor residual spraying (IRS) supported by Mali’s collaboration with the US President’s Malaria Initiative/Africa Indoor Residual Spraying programme. From 2012 to 2015, two different non-pyrethroid insecticides: bendiocarb in 2012 and 2013 and pirimiphos-methyl in 2014 and 2015, were used for IRS in two districts. This report summarizes the results of observational analyses carried out to assess the impact of these IRS campaigns on malaria incidence rates reported through local and district health systems before and after spraying. A series of retrospective time series analyses were performed on 1,382,202 rapid diagnostic test-confirmed cases of malaria reported by district routine health systems in Ségou Region from January 2012 to January 2016. Malaria testing, treatment, surveillance and reporting activities remained consistent across districts and years during the study period, as did LLIN access and use estimates as well as An. gambiae s.l. insecticide resistance patterns. Districts were stratified by IRS implementation status and all-age monthly incidence rates were calculated and compared across strata from 2012 to 2014. In 2015 a regional but variable scale-up of seasonal malaria chemoprevention complicated the region-wide analysis; however IRS operations were suspended in Bla District that year so a difference in differences approach was used to compare 2014 to 2015 changes in malaria incidence at the health facility level in children under 5-years-old from Bla relative to changes observed in Barouéli, where IRS operations were consistent. During 2012–2014, rapid reductions in malaria incidence were observed during the 6 months following each IRS campaign, though most of the reduction in cases (70% of the total) was concentrated in the first 2 months after each campaign was completed. Compared to non-IRS districts, in which normal seasonal patterns of malaria incidence were observed, an estimated 286,745 total fewer cases of all-age malaria were observed in IRS districts. The total cost of IRS in Ségou was around 9.68 million USD, or roughly 33.75 USD per case averted. Further analysis suggests that the timing of the 2012–2014 IRS campaigns (spraying in July and August) was well positioned to maximize public health impact. Suspension of IRS in Bla District after the 2014 campaign resulted in a 70% increase in under-5-years-old malaria incidence rates from 2014 to 2015, significantly greater (p = 0.0003) than the change reported from Barouéli District, where incidence rates remained the same. From 2012 to 2015, the annual IRS campaigns in Ségou are associated with several hundred thousand fewer cases of malaria. This work supports the growing evidence that shows that IRS with non-pyrethroid insecticides is a wise public health investment in areas with documented pyrethroid resistance, high rates of LLIN coverage, and where house structures and population densities are appropriate. Additionally, this work highlights the utility of quality-assured and validated routine surveillance and well defined observational analyses to rapidly assess the impact of malaria control interventions in operational settings, helping to empower evidence-based decision making and to further grow the evidence base needed to better understand when and where to utilize new vector control tools as they become available.