Amy C. Morrison

Defining Challenges and Proposing Solutions for Control of the Virus Vector Aedes aegypti

If done properly, say the authors,Aedes aegypti suppression is a practical method to control urban dengue, yellow fever, and chikungunya viruses.

The Role of Human Movement in the Transmission of Vector-Borne Pathogens

Background 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. Methodology and Principal Findings 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 (R0) of 1.3 when exposure is assumed to occur only in the home versus 3.75 when exposure at multiple locations—e.g., market, friends—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 R0 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. Conclusions/Significance 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.

Characteristics of the Spatial Pattern of the Dengue Vector, Aedes aegypti , in Iquitos, Peru

We determine the spatial pattern of Aedes aegypti and the containers in which they develop in two neighborhoods of the Amazonian city of Iquitos, Peru. Four variables were examined: adult Ae. aegypti, pupae, containers positive for larvae or pupae, and all water-holding containers. Adults clustered strongly within houses and weakly to a distance of 30 meters beyond the household; clustering was not detected beyond 10 meters for positive containers or pupae. Over short periods of time restricted flight range and frequent blood-feeding behavior of Ae. aegypti appear to be underlying factors in the clustering patterns of human dengue infections. Permanent, consistently infested containers (key premises) were not major producers of Ae. aegypti, indicating that larvaciding strategies by themselves may be less effective than reduction of mosquito development sites by source reduction and education campaigns. We conclude that entomologic risk of human dengue infection should be assessed at the household level at frequent time intervals.

Spatial and Temporal Clustering of Dengue Virus Transmission in Thai Villages

Background Transmission of dengue viruses (DENV), the leading cause of arboviral disease worldwide, is known to vary through time and space, likely owing to a combination of factors related to the human host, virus, mosquito vector, and environment. An improved understanding of variation in transmission patterns is fundamental to conducting surveillance and implementing disease prevention strategies. To test the hypothesis that DENV transmission is spatially and temporally focal, we compared geographic and temporal characteristics within Thai villages where DENV are and are not being actively transmitted. Methods and Findings Cluster investigations were conducted within 100 m of homes where febrile index children with (positive clusters) and without (negative clusters) acute dengue lived during two seasons of peak DENV transmission. Data on human infection and mosquito infection/density were examined to precisely (1) define the spatial and temporal dimensions of DENV transmission, (2) correlate these factors with variation in DENV transmission, and (3) determine the burden of inapparent and symptomatic infections. Among 556 village children enrolled as neighbors of 12 dengue-positive and 22 dengue-negative index cases, all 27 DENV infections (4.9% of enrollees) occurred in positive clusters (p < 0.01; attributable risk [AR] = 10.4 per 100; 95% confidence interval 1–19.8 per 100]. In positive clusters, 12.4% of enrollees became infected in a 15-d period and DENV infections were aggregated centrally near homes of index cases. As only 1 of 217 pairs of serologic specimens tested in positive clusters revealed a recent DENV infection that occurred prior to cluster initiation, we attribute the observed DENV transmission subsequent to cluster investigation to recent DENV transmission activity. Of the 1,022 female adult Ae. aegypti collected, all eight (0.8%) dengue-infected mosquitoes came from houses in positive clusters; none from control clusters or schools. Distinguishing features between positive and negative clusters were greater availability of piped water in negative clusters (p < 0.01) and greater number of Ae. aegypti pupae per person in positive clusters (p = 0.04). During primarily DENV-4 transmission seasons, the ratio of inapparent to symptomatic infections was nearly 1:1 among child enrollees. Study limitations included inability to sample all children and mosquitoes within each cluster and our reliance on serologic rather than virologic evidence of interval infections in enrollees given restrictions on the frequency of blood collections in children. Conclusions Our data reveal the remarkably focal nature of DENV transmission within a hyperendemic rural area of Thailand. These data suggest that active school-based dengue case detection prompting local spraying could contain recent virus introductions and reduce the longitudinal risk of virus spread within rural areas. Our results should prompt future cluster studies to explore how host immune and behavioral aspects may impact DENV transmission and prevention strategies. Cluster methodology could serve as a useful research tool for investigation of other temporally and spatially clustered infectious diseases.

House-to-house human movement drives dengue virus transmission

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.

Longitudinal Studies of Aedes aegypti (Diptera: Culicidae) in Thailand and Puerto Rico: Population Dynamics

Abstract Aspiration collections of adult Aedes aegypti (L.) were made weekly from inside and outside of houses for 3 yr in a rural Thai village (n = 9,637 females and n = 11,988 males) and for 2 yr in a residential section of San Juan, Puerto Rico (n = 5,941 females and n = 6,739 males). In Thailand, temperature and rainfall fell into distinct seasonal categories, but only temperature was correlated with fluctuations in female abundance. Average weekly temperature 6 wk before mosquitoes were collected and minimum weekly temperature during the week of collection provided the highest correlations with female abundance. Accounting for annual variation significantly improved Thai models of temperature and mosquito abundance. In Puerto Rico, temperature, but not rainfall, could be categorized into seasonal patterns. Neither was correlated with changes in female abundance. At both sites the vast majority of females were collected inside houses and most contained a blood meal. Most teneral females were collected outside. Wing length—an indicator of female size—and parity, egg development or engorgement status were not correlated, indicating that feeding success and survival were not influenced by female size. At both sites, females fed almost exclusively on human hosts (≥96%), a pattern that did not change seasonally. In Puerto Rico more nonhuman blood meals were detected in mosquitoes collected outside than inside houses; no such difference was detected in Thailand. Gut contents of dissected females indicated that females in the Thai population had a younger age distribution and fed more frequently on blood than did Ae. aegypti in Puerto Rico. Our results indicated that aspects of this species’ biology can vary significantly from one location to another and 1 yr to the next.

Temporal and Geographic Patterns of Aedes aegypti (Diptera: Culicidae) Production in Iquitos, Peru

Abstract Large-scale longitudinal cohort studies are necessary to characterize temporal and geographic variation in Aedes aegypti (L.) (Diptera: Culicidae) production patterns and to develop targeted dengue control strategies that will reduce disease. We carried out pupal/demographic surveys in a circuit of ≈6,000 houses, 10 separate times, between January 1999 and August 2002 in the Amazonian city of Iquitos, Peru. We quantified the number of containers positive for Ae. aegypti larvae and/or pupae, containers holding pupae, and the absolute number of pupae by 4-mo sampling circuits and spatially by geographic area by using a geographic information system developed for the city. A total of 289,941 water-holding containers were characterized, of which 7.3% were positive for Ae. aegypti. Temporal and geographic variations were detected for all variables examined, and the relative importance of different container types for production of Ae. aegypti was calculated. Ae. aegypti larvae and pupae were detected in 64 types of containers. Consistent production patterns were observed for the lid status (lids: 32% wet containers, 2% pupal production), container location (outdoor: 43% wet containers, 85% pupal production), and method by which the container was filled with water (rain filled: 15% wet containers, 88.3% pupal production); these patterns were consistent temporally and geographically. We describe a new container category (nontraditional) that includes transient puddles, which were rare but capable of producing large numbers of pupae. Because of high variable pupal counts, four container categories (large tank, medium storage, miscellaneous, and nontraditional) should be targeted in addition to outdoor rain-filled containers that are not covered by a lid. The utility of targeted Ae. aegypti control is discussed, as well as the ability to achieve control objectives based on published but untested threshold values.

Arboviral etiologies of acute febrile illnesses in Western South America, 2000-2007.

Background Arthropod-borne viruses (arboviruses) are among the most common agents of human febrile illness worldwide and the most important emerging pathogens, causing multiple notable epidemics of human disease over recent decades. Despite the public health relevance, little is know about the geographic distribution, relative impact, and risk factors for arbovirus infection in many regions of the world. Our objectives were to describe the arboviruses associated with acute undifferentiated febrile illness in participating clinics in four countries in South America and to provide detailed epidemiological analysis of arbovirus infection in Iquitos, Peru, where more extensive monitoring was conducted. Methodology/Findings A clinic-based syndromic surveillance system was implemented in 13 locations in Ecuador, Peru, Bolivia, and Paraguay. Serum samples and demographic information were collected from febrile participants reporting to local health clinics or hospitals. Acute-phase sera were tested for viral infection by immunofluorescence assay or RT-PCR, while acute- and convalescent-phase sera were tested for pathogen-specific IgM by ELISA. Between May 2000 and December 2007, 20,880 participants were included in the study, with evidence for recent arbovirus infection detected for 6,793 (32.5%). Dengue viruses (Flavivirus) were the most common arbovirus infections, totaling 26.0% of febrile episodes, with DENV-3 as the most common serotype. Alphavirus (Venezuelan equine encephalitis virus [VEEV] and Mayaro virus [MAYV]) and Orthobunyavirus (Oropouche virus [OROV], Group C viruses, and Guaroa virus) infections were both observed in approximately 3% of febrile episodes. In Iquitos, risk factors for VEEV and MAYV infection included being male and reporting to a rural (vs urban) clinic. In contrast, OROV infection was similar between sexes and type of clinic. Conclusions/Significance Our data provide a better understanding of the geographic range of arboviruses in South America and highlight the diversity of pathogens in circulation. These arboviruses are currently significant causes of human illness in endemic regions but also have potential for further expansion. Our data provide a basis for analyzing changes in their ecology and epidemiology.

A Critical Assessment of Vector Control for Dengue Prevention

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 PDCs 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.

Using Adult Mosquitoes to Transfer Insecticides to Aedes Aegypti Larval Habitats

Vector control is a key means of combating mosquito-borne diseases and the only tool available for tackling the transmission of dengue, a disease for which no vaccine, prophylaxis, or therapeutant currently exists. The most effective mosquito control methods include a variety of insecticidal tools that target adults or juveniles. Their successful implementation depends on impacting the largest proportion of the vector population possible. We demonstrate a control strategy that dramatically improves the efficiency with which high coverage of aquatic mosquito habitats can be achieved. The method exploits adult mosquitoes as vehicles of insecticide transfer by harnessing their fundamental behaviors to disseminate a juvenile hormone analogue (JHA) between resting and oviposition sites. A series of field trials undertaken in an Amazon city (Iquitos, Peru) showed that the placement of JHA dissemination stations in just 3–5% of the available resting area resulted in almost complete coverage of sentinel aquatic habitats. More than control mortality occurred in 95–100% of the larval cohorts of Aedes aegypti developing at those sites. Overall reductions in adult emergence of 42–98% were achieved during the trials. A deterministic simulation model predicts amplifications in coverage consistent with our observations and highlights the importance of the residual activity of the insecticide for this technique.