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Vector-borne diseases (VBDs) such as malaria, dengue, and leishmaniasis exert a huge burden of morbidity and mortality worldwide, particularly affecting the poorest of the poor. The principal method by which these diseases are controlled is through vector control, which has a long and distinguished history. Vector control, to a greater extent than drugs or vaccines, has been responsible for shrinking the map of many VBDs. Here, we describe the history of vector control programmes worldwide from the late 1800s to date. Pre 1940, vector control relied on a thorough understanding of vector ecology and epidemiology, and implementation of environmental management tailored to the ecology and behaviour of local vector species. This complex understanding was replaced by a simplified dependency on a handful of insecticide-based tools, particularly for malaria control, without an adequate understanding of entomology and epidemiology and without proper monitoring and evaluation. With the rising threat from insecticide-resistant vectors, global environmental change, and the need to incorporate more vector control interventions to eliminate these diseases, we advocate for continued investment in evidence-based vector control. There is a need to return to vector control approaches based on a thorough knowledge of the determinants of pathogen transmission, which utilise a range of insecticide and non-insecticide-based approaches in a locally tailored manner for more effective and sustainable vector control.

For decades, arboviral diseases were considered to be only minor contributors to global mortality and disability. As a result, low priority was given to arbovirus research investment and related public health infrastructure. The past five decades, however, have seen an unprecedented emergence of epidemic arboviral diseases (notably dengue, chikungunya, yellow fever, and Zika virus disease) resulting from the triad of the modern world: urbanisation, globalisation, and international mobility. The public health emergency of Zika virus, and the threat of global spread of yellow fever, combined with the resurgence of dengue and chikungunya, constitute a wake-up call for governments, academia, funders, and WHO to strengthen programmes and enhance research in aedes-transmitted diseases. The common features of these diseases should stimulate similar research themes for diagnostics, vaccines, biological targets and immune responses, environmental determinants, and vector control measures. Combining interventions known to be effective against multiple arboviral diseases will offer the most cost-effective and sustainable strategy for disease reduction. New global alliances are needed to enable the combination of efforts and resources for more effective and timely solutions.

Recently, the Vaccines to Vaccinate (v2V) initiative was reconfigured into the Partnership for Dengue Control (PDC), a multi-sponsored and independent initiative. This redirection is consistent with the growing consensus among the dengue-prevention community that no single intervention will be sufficient to control dengue disease. The PDC's expectation is that when an effective dengue virus (DENV) vaccine is commercially available, the public health community will continue to rely on vector control because the two strategies complement and enhance one another. Although the concept of integrated intervention for dengue prevention is gaining increasingly broader acceptance, to date, no consensus has been reached regarding the details of how and what combination of approaches can be most effectively implemented to manage disease. To fill that gap, the PDC proposed a three step process: (1) a critical assessment of current vector control tools and those under development, (2) outlining a research agenda for determining, in a definitive way, what existing tools work best, and (3) determining how to combine the best vector control options, which have systematically been defined in this process, with DENV vaccines. To address the first step, the PDC convened a meeting of international experts during November 2013 in Washington, DC, to critically assess existing vector control interventions and tools under development. This report summarizes those deliberations.

The dramatic global expansion of Aedes albopictus in the last three decades has increased public health concern because it is a potential vector of numerous arthropod-borne viruses (arboviruses), including the most prevalent arboviral pathogen of humans, dengue virus (DENV). Ae. aegypti is considered the primary DENV vector and has repeatedly been incriminated as a driving force in dengue's worldwide emergence. What remains unresolved is the extent to which Ae. albopictus contributes to DENV transmission and whether an improved understanding of its vector status would enhance dengue surveillance and prevention. To assess the relative public health importance of Ae. albopictus for dengue, we carried out two complementary analyses. We reviewed its role in past dengue epidemics and compared its DENV vector competence with that of Ae. aegypti. Observations from \"natural experiments\" indicate that, despite seemingly favorable conditions, places where Ae. albopictus predominates over Ae. aegypti have never experienced a typical explosive dengue epidemic with severe cases of the disease. Results from a meta-analysis of experimental laboratory studies reveal that although Ae. albopictus is overall more susceptible to DENV midgut infection, rates of virus dissemination from the midgut to other tissues are significantly lower in Ae. albopictus than in Ae. aegypti. For both indices of vector competence, a few generations of mosquito colonization appear to result in a relative increase of Ae. albopictus susceptibility, which may have been a confounding factor in the literature. Our results lead to the conclusion that Ae. albopictus plays a relatively minor role compared to Ae. aegypti in DENV transmission, at least in part due to differences in host preferences and reduced vector competence. Recent examples of rapid arboviral adaptation to alternative mosquito vectors, however, call for cautious extrapolation of our conclusion. Vector status is a dynamic process that in the future could change in epidemiologically important ways.

Dengue is a growing problem both in its geographical spread and in its intensity, and yet current global distribution remains highly uncertain. Challenges in diagnosis and diagnostic methods as well as highly variable national health systems mean no single data source can reliably estimate the distribution of this disease. As such, there is a lack of agreement on national dengue status among international health organisations. Here we bring together all available information on dengue occurrence using a novel approach to produce an evidence consensus map of the disease range that highlights nations with an uncertain dengue status. A baseline methodology was used to assess a range of evidence for each country. In regions where dengue status was uncertain, additional evidence types were included to either clarify dengue status or confirm that it is unknown at this time. An algorithm was developed that assesses evidence quality and consistency, giving each country an evidence consensus score. Using this approach, we were able to generate a contemporary global map of national-level dengue status that assigns a relative measure of certainty and identifies gaps in the available evidence. The map produced here provides a list of 128 countries for which there is good evidence of dengue occurrence, including 36 countries that have previously been classified as dengue-free by the World Health Organization and/or the US Centers for Disease Control. It also identifies disease surveillance needs, which we list in full. The disease extents and limits determined here using evidence consensus, marks the beginning of a five-year study to advance the mapping of dengue virus transmission and disease risk. Completion of this first step has allowed us to produce a preliminary estimate of population at risk with an upper bound of 3.97 billion people. This figure will be refined in future work.

Ronald Ross and George Macdonald are credited with developing a mathematical model of mosquito-borne pathogen transmission. A systematic historical review suggests that several mathematicians and scientists contributed to development of the Ross-Macdonald model over a period of 70 years. Ross developed two different mathematical models, Macdonald a third, and various \"Ross-Macdonald\" mathematical models exist. Ross-Macdonald models are best defined by a consensus set of assumptions. The mathematical model is just one part of a theory for the dynamics and control of mosquito-transmitted pathogens that also includes epidemiological and entomological concepts and metrics for measuring transmission. All the basic elements of the theory had fallen into place by the end of the Global Malaria Eradication Programme (GMEP, 1955-1969) with the concept of vectorial capacity, methods for measuring key components of transmission by mosquitoes, and a quantitative theory of vector control. The Ross-Macdonald theory has since played a central role in development of research on mosquito-borne pathogen transmission and the development of strategies for mosquito-borne disease prevention.

The public health burden of dengue is unknown; here cartographic approaches are used to provide insight into the global, regional and national burden of dengue, with the finding that the global number of infections per year is around 390 million, more than three times the estimate of the World Health Organization. Mapping the spread of dengue The mosquito-borne viral infection dengue is found in tropical and subtropical regions worldwide, predominantly in urban and semi-urban areas. The incidence of dengue is on the increase, but the current global distribution is poorly known. Simon Hay and colleagues have applied novel mapping techniques to an extensive evidence base of nearly 10,000 case records. The outcome is an estimate of around 390 million new infections per year, more than double the most recent estimate from the World Health Organization. Importantly, this work extends the mapping to provide global estimates of the symptomatic and asymptomatic dengue case burden, at 96 and 294 million, respectively. Dengue is a systemic viral infection transmitted between humans by Aedes mosquitoes 1 . For some patients, dengue is a life-threatening illness 2 . There are currently no licensed vaccines or specific therapeutics, and substantial vector control efforts have not stopped its rapid emergence and global spread 3 . The contemporary worldwide distribution of the risk of dengue virus infection 4 and its public health burden are poorly known 2 , 5 . Here we undertake an exhaustive assembly of known records of dengue occurrence worldwide, and use a formal modelling framework to map the global distribution of dengue risk. We then pair the resulting risk map with detailed longitudinal information from dengue cohort studies and population surfaces to infer the public health burden of dengue in 2010. We predict dengue to be ubiquitous throughout the tropics, with local spatial variations in risk influenced strongly by rainfall, temperature and the degree of urbanization. Using cartographic approaches, we estimate there to be 390 million (95% credible interval 284–528) dengue infections per year, of which 96 million (67–136) manifest apparently (any level of disease severity). This infection total is more than three times the dengue burden estimate of the World Health Organization 2 . Stratification of our estimates by country allows comparison with national dengue reporting, after taking into account the probability of an apparent infection being formally reported. The most notable differences are discussed. These new risk maps and infection estimates provide novel insights into the global, regional and national public health burden imposed by dengue. We anticipate that they will provide a starting point for a wider discussion about the global impact of this disease and will help to guide improvements in disease control strategies using vaccine, drug and vector control methods, and in their economic evaluation.

Three-quarters of the estimated 390 million dengue virus (DENV) infections each year are clinically inapparent. People with inapparent dengue virus infections are generally considered dead-end hosts for transmission because they do not reach sufficiently high viremia levels to infect mosquitoes. Here, we show that, despite their lower average level of viremia, asymptomatic people can be infectious to mosquitoes. Moreover, at a given level of viremia, DENV-infected people with no detectable symptoms or before the onset of symptoms are significantly more infectious to mosquitoes than people with symptomatic infections. Because DENV viremic people without clinical symptoms may be exposed to more mosquitoes through their undisrupted daily routines than sick people and represent the bulk of DENV infections, our data indicate that they have the potential to contribute significantlymore to virus transmission to mosquitoes than previously recognized.

Despite estimates that, each year, as many as 300 million dengue virus (DENV) infections result in either no perceptible symptoms (asymptomatic) or symptoms that are sufficiently mild to go undetected by surveillance systems (inapparent), it has been assumed that these infections contribute little to onward transmission. However, recent blood-feeding experiments with Aedes aegypti mosquitoes showed that people with asymptomatic and pre-symptomatic DENV infections are capable of infecting mosquitoes. To place those findings into context, we used models of within-host viral dynamics and human demographic projections to (1) quantify the net infectiousness of individuals across the spectrum of DENV infection severity and (2) estimate the fraction of transmission attributable to people with different severities of disease. Our results indicate that net infectiousness of people with asymptomatic infections is 80% (median) that of people with apparent or inapparent symptomatic infections (95% credible interval (CI): 0-146%). Due to their numerical prominence in the infectious reservoir, clinically inapparent infections in total could account for 84% (CI: 82-86%) of DENV transmission. Of infections that ultimately result in any level of symptoms, we estimate that 24% (95% CI: 0-79%) of onward transmission results from mosquitoes biting individuals during the pre-symptomatic phase of their infection. Only 1% (95% CI: 0.8-1.1%) of DENV transmission is attributable to people with clinically detected infections after they have developed symptoms. These findings emphasize the need to (1) reorient current practices for outbreak response to adoption of pre-emptive strategies that account for contributions of undetected infections and (2) apply methodologies that account for undetected infections in surveillance programs, when assessing intervention impact, and when modeling mosquito-borne virus transmission.

Most studies on the ability of insect populations to transmit pathogens consider only constant temperatures and do not account for realistic daily temperature fluctuations that can impact vector-pathogen interactions. Here, we show that diurnal temperature range (DTR) affects two important parameters underlying dengue virus (DENV) transmission by Aedes aegypti. In two independent experiments using different DENV serotypes, mosquitoes were less susceptible to virus infection and died faster under larger DTR around the same mean temperature. Large DTR (20 °C) decreased the probability of midgut infection, but not duration of the virus extrinsic incubation period (EIP), compared with moderate DTR (10 °C) or constant temperature. A thermodynamic model predicted that at mean temperatures <18 °C, DENV transmission increases as DTR increases, whereas at mean temperatures >18 °C, larger DTR reduces DENV transmission. The negative impact of DTR on Ae. aegypti survival indicates that large temperature fluctuations will reduce the probability of vector survival through EIP and expectation of infectious life. Seasonal variation in the amplitude of daily temperature fluctuations helps to explain seasonal forcing of DENV transmission at locations where average temperature does not vary seasonally and mosquito abundance is not associated with dengue incidence. Mosquitoes lived longer and were more likely to become infected under moderate temperature fluctuations, which is typical of the high DENV transmission season than under large temperature fluctuations, which is typical of the low DENV transmission season. Our findings reveal the importance of considering short-term temperature variations when studying DENV transmission dynamics.