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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.

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.

Background After the unprecedented Zika virus (ZIKV) outbreak in the western hemisphere from 2015-2018, Aedes aegypti and Ae. albopictus are now well established primary and secondary ZIKV vectors, respectively. Consensus about identification and importance of other secondary ZIKV vectors remain. This systematic review aims to provide a list of vector species capable of transmitting ZIKV by reviewing evidence from laboratory vector competence (VC) studies and to identify key knowledge gaps and issues within the ZIKV VC literature. Methods A search was performed until 15.sup.th March 2022 on the Cochrane Library, Lilacs, PubMed, Web of Science, WHOLIS and Google Scholar. The search strings included three general categories: [1] \"ZIKA\"; [2] \"vector\"; [3] \"competence\", \"transmission\", \"isolation\", or \"feeding behavior\" and their combinations. Inclusion and exclusion criteria has been predefined and quality of included articles was assessed by STROBE and STROME-ID criteria. Findings From 8,986 articles retrieved, 2,349 non-duplicates were screened by title and abstracts,103 evaluated using the full text, and 45 included in this analysis. Main findings are 1) secondary vectors of interest include Ae. japonicus, Ae. detritus, and Ae. vexans at higher temperature 2) Culex quinquefasciatus was not found to be a competent vector of ZIKV, 3) considerable heterogeneity in VC, depending on the local mosquito strain and virus used in testing was observed. Critical issues or gaps identified included 1) inconsistent definitions of VC parameters across the literature; 2) equivalency of using different mosquito body parts to evaluate VC parameters for infection (mosquito bodies versus midguts), dissemination (heads, legs or wings versus salivary glands), and transmission (detection or virus amplification in saliva, FTA cards, transmission to neonatal mice); 3) articles that fail to use infectious virus assays to confirm the presence of live virus; 4) need for more studies using murine models with immunocompromised mice to infect mosquitoes. Conclusion Recent, large collaborative multi-country projects to conduct large scale evaluations of specific mosquito species represent the most appropriate approach to establish VC of mosquito species.

Empiric quantification of human mobility patterns is paramount for better urban planning, understanding social network structure and responding to infectious disease threats, especially in light of rapid growth in urbanization and globalization. This need is of particular relevance for developing countries, since they host the majority of the global urban population and are disproportionally affected by the burden of disease. We used Global Positioning System (GPS) data-loggers to track the fine-scale (within city) mobility patterns of 582 residents from two neighborhoods from the city of Iquitos, Peru. We used ∼2.3 million GPS data-points to quantify age-specific mobility parameters and dynamic co-location networks among all tracked individuals. Geographic space significantly affected human mobility, giving rise to highly local mobility kernels. Most (∼80%) movements occurred within 1 km of an individual's home. Potential hourly contacts among individuals were highly irregular and temporally unstructured. Only up to 38% of the tracked participants showed a regular and predictable mobility routine, a sharp contrast to the situation in the developed world. As a case study, we quantified the impact of spatially and temporally unstructured routines on the dynamics of transmission of an influenza-like pathogen within an Iquitos neighborhood. Temporally unstructured daily routines (e.g., not dominated by a single location, such as a workplace, where an individual repeatedly spent significant amount of time) increased an epidemic's final size and effective reproduction number by 20% in comparison to scenarios modeling temporally structured contacts. Our findings provide a mechanistic description of the basic rules that shape human mobility within a resource-poor urban center, and contribute to the understanding of the role of fine-scale patterns of individual movement and co-location in infectious disease dynamics. More generally, this study emphasizes the need for careful consideration of human social interactions when designing infectious disease mitigation strategies, particularly within resource-poor urban environments.

Dengue is a mosquito-borne disease of growing global health importance. Prevention efforts focus on mosquito control, with limited success. New insights into the spatiotemporal drivers of dengue dynamics are needed to design improved disease-prevention strategies. Given the restricted range of movement of the primary mosquito vector, Aedes aegypti , local human movements may be an important driver of dengue virus (DENV) amplification and spread. Using contact-site cluster investigations in a case-control design, we demonstrate that, at an individual level, risk for human infection is defined by visits to places where contact with infected mosquitoes is likely, independent of distance from the home. Our data indicate that house-to-house human movements underlie spatial patterns of DENV incidence, causing marked heterogeneity in transmission rates. At a collective level, transmission appears to be shaped by social connections because routine movements among the same places, such as the homes of family and friends, are often similar for the infected individual and their contacts. Thus, routine, house-to-house human movements do play a key role in spread of this vector-borne pathogen at fine spatial scales. This finding has important implications for dengue prevention, challenging the appropriateness of current approaches to vector control. We argue that reexamination of existing paradigms regarding the spatiotemporal dynamics of DENV and other vector-borne pathogens, especially the importance of human movement, will lead to improvements in disease prevention.

Routine entomological monitoring data are used to quantify the abundance of Ae. aegypti. The public health utility of these indicators is based on the assumption that greater mosquito abundance increases the risk of human DENV transmission, and therefore reducing exposure to the vector decreases incidence of infection. Entomological survey data from two longitudinal cohort studies in Iquitos, Peru, linked with 8,153 paired serological samples taken approximately six months apart were analyzed. Indicators of Ae. aegypti density were calculated from cross-sectional and longitudinal entomological data collected over a 12-month period for larval, pupal and adult Ae. aegypti. Log binomial models were used to estimate risk ratios (RR) to measure the association between Ae. aegypti abundance and the six-month risk of DENV seroconversion. RRs estimated using cross-sectional entomological data were compared to RRs estimated using longitudinal data. Higher cross-sectional Ae. aegypti densities were not associated with an increased risk of DENV seroconversion. Use of longitudinal entomological data resulted in RRs ranging from 1.01 (95% CI: 1.01, 1.02) to 1.30 (95% CI: 1.17, 1.46) for adult stage density estimates and RRs ranging from 1.21 (95% CI: 1.07, 1.37) to 1.75 (95% CI: 1.23, 2.5) for categorical immature indices. Ae. aegypti densities calculated from longitudinal entomological data were associated with DENV seroconversion, whereas those measured cross-sectionally were not. Ae. aegypti indicators calculated from cross-sectional surveillance, as is common practice, have limited public health utility in detecting areas or populations at high risk of DENV infection.

Human movement is a key behavioral factor in many vector-borne disease systems because it influences exposure to vectors and thus the transmission of pathogens. Human movement transcends spatial and temporal scales with different influences on disease dynamics. Here we develop a conceptual model to evaluate the importance of variation in exposure due to individual human movements for pathogen transmission, focusing on mosquito-borne dengue virus. We develop a model showing that the relevance of human movement at a particular scale depends on vector behavior. Focusing on the day-biting Aedes aegypti, we illustrate how vector biting behavior combined with fine-scale movements of individual humans engaged in their regular daily routine can influence transmission. Using a simple example, we estimate a transmission rate (R(0)) of 1.3 when exposure is assumed to occur only in the home versus 3.75 when exposure at multiple locations--e.g., market, friend's--due to movement is considered. Movement also influences for which sites and individuals risk is greatest. For the example considered, intriguingly, our model predicts little correspondence between vector abundance in a site and estimated R(0) for that site when movement is considered. This illustrates the importance of human movement for understanding and predicting the dynamics of a disease like dengue. To encourage investigation of human movement and disease, we review methods currently available to study human movement and, based on our experience studying dengue in Peru, discuss several important questions to address when designing a study. Human movement is a critical, understudied behavioral component underlying the transmission dynamics of many vector-borne pathogens. Understanding movement will facilitate identification of key individuals and sites in the transmission of pathogens such as dengue, which then may provide targets for surveillance, intervention, and improved disease prevention.

Entomological research studies on mosquito vector biology, vector competence, insecticide resistance, dispersal, and survival (using mark-release-recapture techniques) often rely on laboratory-reared mosquito colonies to produce large numbers of consistently reared, aged, and sized mosquitoes. We developed a low-cost blood feeding apparatus that supports temperatures consistent with warm blooded animals, using commonly available materials found in low resource environments. We compare our system (“Caserotek”) to Hemotek and glass/membrane feeding methods. Two experiments were conducted with Aedes aegypti (Linnaeus 1762) and one with Anopheles darlingi (Root 1926) (Diptera: Culicidae); 3 replicates were conducted for each experiment. Aedes aegypti female mosquitoes were provided chicken blood once per week for 30 min (Experiment #1) for 14 days or 1 hour (Experiment #2) for 21 days. Anopheles darlingi were fed once for 1 hour (Experiment #3). Blood-feeding rates, survival rates, and egg production were calculated across replicates. Caserotek had a significantly higher 30-min engorgement rate (91.1%) than Hemotek (47.7%), and the glass feeder (29.3%) whereas for 1-hour feeding, Hemotek had a significantly lower engorgement rate than either of the other two devices (78% versus 91%). Thirty-day survival was similar among the feeding devices, ranging from 86% to 99%. Mean egg production was highest for the Caserotek feeder (32 eggs per female) compared to the glass feeder and Hemotek device (21–22 eggs per female). Our new artificial feeding system had significantly higher blood feeding rates than for more expensive artificial systems and was equivalent to other fitness parameters. Caserotek only requires the ability to boil water to maintain blood temperatures using a Styrofoam liner. It can be easily scaled up to large production facilities and used under austere conditions.

Dengue has historically been considered an urban disease associated with dense human populations and the built environment. Recently, studies suggest increasing dengue virus (DENV) transmission in rural populations. It is unclear whether these reports reflect recent spread into rural areas or ongoing transmission that was previously unnoticed, and what mechanisms are driving this rural transmission. We conducted a systematic review to synthesize research on dengue in rural areas and apply this knowledge to summarize aspects of rurality used in current epidemiological studies of DENV transmission given changing and mixed environments. We described how authors defined rurality and how they defined mechanisms for rural dengue transmission. We systematically searched PubMed, Web of Science, and Embase for articles evaluating dengue prevalence or cumulative incidence in rural areas. A total of 106 articles published between 1958 and 2021 met our inclusion criteria. Overall, 56% ( n = 22) of the 48 estimates that compared urban and rural settings reported rural dengue incidence as being as high or higher than in urban locations. In some rural areas, the force of infection appears to be increasing over time, as measured by increasing seroprevalence in children and thus likely decreasing age of first infection, suggesting that rural dengue transmission may be a relatively recent phenomenon. Authors characterized rural locations by many different factors, including population density and size, environmental and land use characteristics, and by comparing their context to urban areas. Hypothesized mechanisms for rural dengue transmission included travel, population size, urban infrastructure, vector and environmental factors, among other mechanisms. Strengthening our understanding of the relationship between rurality and dengue will require a more nuanced definition of rurality from the perspective of DENV transmission. Future studies should focus on characterizing details of study locations based on their environmental features, exposure histories, and movement dynamics to identify characteristics that may influence dengue transmission.

Early diagnosis of dengue virus (DENV) infection can improve clinical outcomes by ensuring close follow-up, initiating appropriate supportive therapies and raising awareness to the potential of hemorrhage or shock. Non-structural glycoprotein-1 (NS1) has proven to be a useful biomarker for early diagnosis of dengue. A number of rapid diagnostic tests (RDTs) and enzyme-linked immunosorbent assays (ELISAs) targeting NS1 antigen (Ag) are now commercially available. Here we evaluated these tests using a well-characterized panel of clinical samples to determine their effectiveness for early diagnosis. Retrospective samples from South America were used to evaluate the following tests: (i) \"Dengue NS1 Ag STRIP\" and (ii) \"Platelia Dengue NS1 Ag ELISA\" (Bio-Rad, France), (iii) \"Dengue NS1 Detect Rapid Test (1st Generation)\" and (iv) \"DENV Detect NS1 ELISA\" (InBios International, United States), (v) \"Panbio Dengue Early Rapid (1st generation)\" (vi) \"Panbio Dengue Early ELISA (2nd generation)\" and (vii) \"SD Bioline Dengue NS1 Ag Rapid Test\" (Alere, United States). Overall, the sensitivity of the RDTs ranged from 71.9%-79.1% while the sensitivity of the ELISAs varied between 85.6-95.9%, using virus isolation as the reference method. Most tests had lower sensitivity for DENV-4 relative to the other three serotypes, were less sensitive in detecting secondary infections, and appeared to be most sensitive on Day 3-4 post symptom onset. The specificity of all evaluated tests ranged from 95%-100%. ELISAs had greater overall sensitivity than RDTs. In conjunction with other parameters, the performance data can help determine which dengue diagnostics should be used during the first few days of illness, when the patients are most likely to present to a clinic seeking care.