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Background: Human mobility among residential locations can drive dengue virus (DENV) transmission dynamics. Recently, it was shown that individuals with symptomatic DENV infection exhibit significant changes in their mobility patterns, spending more time at home during illness. This change in mobility is predicted to increase the risk of acquiring infection for those living with or visiting the ill individual. It has yet to be considered, however, whether social contacts are also changing their mobility, either by socially distancing themselves from the infectious individual or increasing contact to help care for them. Social, or physical, distancing and caregiving could have diverse yet important impacts on DENV transmission dynamics; therefore, it is necessary to better understand the nature and frequency of these behaviors including their effect on mobility. Methodology and principal findings: Through community-based febrile illness surveillance and RT-PCR infection confirmation, 67 DENV positive (DENV+) residents were identified in the city of Iquitos, Peru. Using retrospective interviews, data were collected on visitors and home-based care received during the illness. While 15% of participants lost visitors during their illness, 22% gained visitors; overall, 32% of all individuals (particularly females) received visitors while symptomatic. Caregiving was common (90%), particularly caring by housemates (91%) and caring for children (98%). Twenty-eight percent of caregivers changed their behavior enough to have their work (and, likely, mobility patterns) affected. This was significantly more likely when caring for individuals with low "health-related quality of well-being" during illness (Fisher's Exact, p = 0.01). Conclusions/Significance: Our study demonstrates that social contacts of individuals with dengue modify their patterns of visitation and caregiving. The observed mobility changes could impact a susceptible individual's exposure to virus or a presymptomatic/clinically inapparent individual's contribution to onward transmission. Accounting for changes in social contact mobility is imperative in order to get a more accurate understanding of DENV transmission. Author summary: Dengue is the most important mosquito-borne viral disease of humans worldwide. Due to the limited mobility of the mosquitoes that transmit dengue virus, human mobility is a key variable to understanding the spread of dengue through a population. Recently it was shown that individuals with symptomatic dengue have significantly reduced mobility patterns. To better understand how dengue illness affects the behavior of visitors and caregivers, we examined the nature and frequency of a symptomatic individual's social contacts to determine if their behaviors changed due to social distancing or caregiving. While many participants had a drop off in visitor frequency when ill, almost all participants received help from their housemates. These caregivers were most likely to have their work impacted when helping participants whose quality of life was most negatively affected by illness. We quantified how often these behavioral changes had a discernable effect on the social contact's mobility patterns. Accounting for mobility changes by social contacts provides a more accurate understanding of infection risk and potential for virus spread through a population. Dengue transmission models that incorporate mobility changes of symptomatic individuals and their social contacts will add currently missing epidemiologically relevant detail for evaluating different disease prevention strategies. [ABSTRACT FROM AUTHOR]

Measuring heterogeneity of dengue illness is necessary to define suitable endpoints in dengue vaccine and therapeutic trials and will help clarify behavioral responses to illness. To quantify heterogeneity in dengue illness, including milder cases, we developed the Dengue Illness Perceptions Response (IPR) survey, which captured detailed symptom data, including intensity, duration, and character, and change in routine activities caused by illness. During 2016-2019, we collected IPR data daily during the acute phase of illness for 79 persons with a positive reverse transcription PCR result for dengue virus RNA. Most participants had mild ambulatory disease. However, we measured substantial heterogeneity in illness experience, symptom duration, and maximum reported intensity of individual symptoms. Symptom intensity was a more valuable predicter of major activity change during dengue illness than symptom presence or absence alone. These data suggest that the IPR measures clinically useful heterogeneity in dengue illness experience and its relation to altered human behavior. [ABSTRACT FROM AUTHOR]

Previous studies measuring the health-related quality of life (HRQoL) of individuals with dengue focused on treatment seeking populations. However, the vast majority of global dengue cases are unlikely to be detected by health systems. Representative measurements of HRQoL should therefore include patients with disease not likely to trigger treatment-seeking behavior. This study based in Iquitos, Peru used the Quality of Wellbeing Scale-Self Administered, a survey that enquires about not only physical health, but also psychological health, self-care, mobility, and usual social activities, and rates HRQoL between 0 (death) and 1 (optimum function), to evaluate the impact of dengue on HRQoL. In order to enroll treatment and non treatment-seeking participants, three modalities of participant recruitment were used. In addition to clinic and community-based febrile surveillance, a contact-cluster methodology was also employed to identify infected individuals less likely to seek treatment. We measured changes in HRQoL and identified common areas of health impairment in 73 virologically confirmed dengue cases at 3 time points during the participant's illness; the early-acute (days 0–6 post symptom onset), late-acute (days 7–20), and convalescent illness phases (days 21 +). Participants reported HRQoL related impairments at significantly higher frequency during the early-acute versus convalescent illness phase (Fisher's exact: P<0.01). There was substantial heterogeneity in scores during each illness phase with median scores in the early-acute, late-acute and convalescent phases of 0.56 (IQR: 0.41–0.64), 0.70 (IQR: 0.57–0.94), and 1 (IQR: 0.80–1.00), respectively. In all illness phases participants recruited in clinics had on average the lowest HRQoL scores where as those recruited in the contact clusters had the highest. Only 1 individual who was recruited in the contact-clusters had no reduction in HRQoL score during their illness. These data illustrate that dengue should be considered as a disease that may have significant implications for not only physical health but also psychological health and social functioning. The impact of dengue on the HRQoL of non-treatment-seeking individuals, although lower than the impact among treatment-seeking individuals, is not necessarily trivial. Author summary: Dengue, a viral illness occurring following the bite of an infected mosquito, is common in tropical urban areas of the globe. Using a survey that enquires about not only physical health but also psychological health, self-care, mobility and usual social activities, this study assesses the overall impact of dengue on the well-being of those with the disease. Of the estimated 390 million annual infections, approximately 75 percent do not cause individuals to attend medical facilities, possibly because many infections do not result in significant symptoms or because access to healthcare is limited. Unlike previous studies, this study recruited those who would have been unlikely to seek healthcare as well as individuals who attended health facilities. This study adds to the growing body of evidence that healthcare professionals should regard dengue as a disease that affects not only physical, but also psychological health and aspects of social functioning. Furthermore, it suggests that those not seeking treatment may also have a substantial reduction in quality of life during their infection. Given the millions of dengue infected people who do not attend healthcare facilities annually this could amount to a very meaningful societal impact. [ABSTRACT FROM AUTHOR]

Dengue is one of the most important vector-borne diseases, resulting in an estimated hundreds of millions of infections annually throughout the tropics. Control of dengue is heavily dependent upon control of its primary mosquito vector, Aedes aegypti. Innovative interventions that are effective at targeting the adult stage of the mosquito are needed to increase the options for effective control. The use of insecticide-treated curtains (ITCs) has previously been shown to significantly reduce the abundance of Ae. aegypti in and around homes, but the impact of ITCs on dengue virus (DENV) transmission has not been rigorously quantified. A parallel arm cluster-randomized controlled trial was conducted in Iquitos, Peru to quantify the impact of ITCs on DENV seroconversion as measured through plaque-reduction neutralization tests. Seroconversion data showed that individuals living in the clusters that received ITCs were at greater risk to seroconverting to DENV, with an average seroconversion rate of 50.6 per 100 person-years (PY) (CI: 29.9–71.9), while those in the control arm had an average seroconversion rate of 37.4 per 100 PY (CI: 15.2–51.7). ITCs lost their insecticidal efficacy within 6 months of deployment, necessitating re-treatment with insecticide. Entomological indicators did not show statistically significant differences between ITC and non-ITC clusters. It's unclear how the lack of protective efficacy reported here is attributable to simple failure of the intervention to protect against Ae. aegypti bites, or the presence of a faulty intervention during much of the follow-up period. The higher risk of dengue seroconversion that was detected in the ITC clusters may have arisen due to a false sense of security that inadvertently led to less routine protective behaviors on the part of households that received the ITCs. Our study provides important lessons learned for conducting Randomized Cluster Trials for vector control interventions against Aedes-transmitted virus infections. Author summary: Dengue is one of the most important mosquito-borne diseases effecting humans, resulting in an estimated hundreds of millions of infections annually throughout the tropics. To control dengue, most public health programs use a variety of methods to kill the primary mosquito vector, Aedes aegypti. Water holding containers that harbor larvae (and other immature stages) are treated or eliminated. During emergencies, large insecticide spray campaigns are deployed to kill infected adult mosquitoes. Innovative interventions that are effective at targeting adult mosquitoes in sustainable ways are needed to increase the options for control of dengue and other Aedes borne virus diseases. The use of insecticide-treated curtains (ITCs) has previously been shown to significantly reduce Ae. aegypti numbers in and around homes, but the impact of ITCs on dengue virus (DENV) transmission has not previously been quantified. Using a rigorous study design in which 10 clusters (~90 houses per cluster) were provided multiple ITCs to place in their homes was compared to 10 clusters of homes without ITCs. Assignment of which clusters received ITCs was randomized. Blood samples were obtained at 9-month intervals from residents living in all the clusters, so that people with serological evidence of a DENV infection could be identified by comparing paired samples. Seroconversion data showed that individuals living in the clusters that received ITCs were at greater risk to DENV seroconverting, with an average seroconversion rate of 50.6 per 100 person-years (PY) (CI: 29.9–71.9). Conversely, those in the control arm had an average seroconversion rate of 37.4 per 100 PY (CI: 15.2–51.7). ITCs lost their insecticidal efficacy within 6 months of deployment, necessitating re-treatment with insecticide. Ae. aegypti populations did not show statistically significant differences between ITC and non-ITC clusters. The reason for higher transmission in the ITC treated clusters could be attributable to failure of the curtains (loss of efficacy) and/or that the curtains were not sufficiently effective at protecting against mosquito bites. The higher risk of DENV seroconversion in ITC clusters may be due to a false sense of security that inadvertently led to less routine protective behaviors on the part of households that received the ITC. [ABSTRACT FROM AUTHOR]

Background: Dengue is an arthropod-borne viral disease responsible for approximately 400 million infections annually; the only available method of prevention is vector control. It has been previously demonstrated that insecticide treated curtains (ITCs) can lower dengue vector infestations in and around houses. As part of a larger trial examining whether ITCs could reduce dengue transmission in Iquitos, Peru, the objective of this study was to characterize the participants' experience with the ITCs using qualitative methods.Methods: Knowledge, attitudes, and practices (KAP) surveys (at baseline, and 9 and 27 months post-ITC distribution, with n = 593, 595 and 511, respectively), focus group discussions (at 6 and 12 months post-ITC distribution, with n = 18 and 33, respectively), and 11 one-on-one interviews (at 12 months post-distribution) were conducted with 605 participants who received ITCs as part of a cluster-randomized trial.Results: Focus groups at 6 months post-ITC distribution revealed that individuals had observed their ITCs to function for approximately 3 months, after which they reported the ITCs were no longer working. Follow up revealed that the ITCs required re-treatment with insecticide at approximately 1 year post-distribution. Over half (55.3 %, n = 329) of participants at 9 months post-ITC distribution and over a third (34.8 %, n = 177) at 27 months post-ITC distribution reported perceiving a decrease in the number of mosquitoes in their home. The percentage of participants who would recommend ITCs to their family or friends in the future remained high throughout the study (94.3 %, n = 561 at 9 months and 94.6 %, n = 488 at 27 months post-distribution). When asked why, participants reported that ITCs were effective at reducing mosquitoes (81.6 and 37.8 %, at 9 and 27 months respectively), that they prevent dengue (5.7 and 51.2 %, at 9 and 27 months), that they are "beautiful" (5.9 and 3.1 %), as well as other reasons (6.9 and 2.5 %).Conclusion: ITCs have substantial potential for long term dengue vector control because they are liked by users, both for their perceived effectiveness and for aesthetic reasons, and because they require little proactive behavioral effort on the part of the users. Our results highlight the importance of gathering process (as opposed to outcome) data during vector control studies, without which researchers would not have become aware that the ITCs had lost effectiveness early in the trial. [ABSTRACT FROM AUTHOR]

Background: Empiric evidence shows that Aedes aegypti abundance is spatially heterogeneous and that some areas and larval habitats produce more mosquitoes than others. There is a knowledge gap, however, with regards to the temporal persistence of such Ae. aegypti abundance hotspots. In this study, we used a longitudinal entomologic dataset from the city of Iquitos, Peru, to (1) quantify the spatial clustering patterns of adult Ae. aegypti and pupae counts per house, (2) determine overlap between clusters, (3) quantify the temporal stability of clusters over nine entomologic surveys spaced four months apart, and (4) quantify the extent of clustering at the household and neighborhood levels. Methodologies/Principal Findings: Data from 13,662 household entomological visits performed in two Iquitos neighborhoods differing in Ae. aegypti abundance and dengue virus transmission was analyzed using global and local spatial statistics. The location and extent of Ae. aegypti pupae and adult hotspots (i.e., small groups of houses with significantly [p<0.05] high mosquito abundance) were calculated for each of the 9 entomologic surveys. The extent of clustering was used to quantify the probability of finding spatially correlated populations. Our analyses indicate that Ae. aegypti distribution was highly focal (most clusters do not extend beyond 30 meters) and that hotspots of high vector abundance were common on every survey date, but they were temporally unstable over the period of study. Conclusions/Significance: Our findings have implications for understanding Ae. aegypti distribution and for the design of surveillance and control activities relying on household-level data. In settings like Iquitos, where there is a relatively low percentage of Ae. aegypti in permanent water-holding containers, identifying and targeting key premises will be significantly challenged by shifting hotspots of Ae. aegypti infestation. Focusing efforts in large geographic areas with historically high levels of transmission may be more effective than targeting Ae. aegypti hotspots. Author Summary: We carried out a comprehensive study of the long-term trends in household-level Aedes aegypti spatial distribution within a well-defined urban area endemic for dengue virus. By using a dataset consisting of 13,662 household entomological visits performed in two neighborhoods in Iquitos, Peru, we quantified the ∼3 year spatial clustering patterns of Ae. aegypti among houses and the temporal persistence of vector abundance hotspots. Our results provide strong support for the conclusion that Ae. aegypti distribution is highly focal and that hotspots of high vector abundance at the level of small groups of houses are common, but temporally unstable. Results from our study have implications for understanding the spatio-temporal patterns of Ae. aegypti abundance and for the design of surveillance and control activities that are based on household-level entomological data. [ABSTRACT FROM AUTHOR]

Quantifying human mobility has significant consequences for studying physical activity, exposure to pathogens, and generating more realistic infectious disease models. Location-aware technologies such as Global Positioning System (GPS)-enabled devices are used increasingly as a gold standard for mobility research. The main goal of this observational study was to compare and contrast the information obtained through GPS and semi-structured interviews (SSI) to assess issues affecting data quality and, ultimately, our ability to measure fine-scale human mobility. A total of 160 individuals, ages 7 to 74, from Iquitos, Peru, were tracked using GPS data-loggers for 14 days and later interviewed using the SSI about places they visited while tracked. A total of 2,047 and 886 places were reported in the SSI and identified by GPS, respectively. Differences in the concordance between methods occurred by location type, distance threshold (within a given radius to be considered a match) selected, GPS data collection frequency (i.e., 30, 90 or 150 seconds) and number of GPS points near the SSI place considered to define a match. Both methods had perfect concordance identifying each participant's house, followed by 80–100% concordance for identifying schools and lodgings, and 50–80% concordance for residences and commercial and religious locations. As the distance threshold selected increased, the concordance between SSI and raw GPS data increased (beyond 20 meters most locations reached their maximum concordance). Processing raw GPS data using a signal-clustering algorithm decreased overall concordance to 14.3%. The most common causes of discordance as described by a sub-sample (n = 101) with whom we followed-up were GPS units being accidentally off (30%), forgetting or purposely not taking the units when leaving home (24.8%), possible barriers to the signal (4.7%) and leaving units home to recharge (4.6%). We provide a quantitative assessment of the strengths and weaknesses of both methods for capturing fine-scale human mobility. Author Summary: Being able to quantify human movement is important for studying activity patterns, exposure to pathogens and developing realistic infectious disease models. We compared fine-scale human mobility data obtained by Global Positioning System (GPS)-enabled devices and semi-structured interviews (SSI) from 160 individuals in Iquitos, Peru, in order to assess the quality of data using these two different approaches and our ability to measure fine-scale human mobility patterns in a resource-poor urban environment. Using various methods to process the GPS data, we found the SSI identified more locations a person had visited than GPS. Though the GPS gave more precise data, there were behavioral, technical, and analytical barriers. The SSI provided richer context and was easier to process, but also had more false positives. SSI was the only option for identifying locations retrospectively. [ABSTRACT FROM AUTHOR]

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, 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 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. Author Summary: Vector-borne diseases constitute a largely neglected and enormous burden on public health in many resource-challenged environments, demanding efficient control strategies that could be developed through improved understanding of pathogen transmission. Human movement—which determines exposure to vectors—is a key behavioral component of vector-borne disease epidemiology that is poorly understood. We develop a conceptual framework to organize past studies by the scale of movement and then examine movements at fine-scale—i.e., people going through their regular, daily routine—that determine exposure to insect vectors for their role in the dynamics of pathogen transmission. We develop a model to quantify risk of vector contact across locations people visit, with emphasis on mosquito-borne dengue virus in the Amazonian city of Iquitos, Peru. An example scenario illustrates how movement generates variation in exposure risk across individuals, how transmission rates within sites can be increased, and that risk within sites is not solely determined by vector density, as is commonly assumed. Our analysis illustrates the importance of human movement for pathogen transmission, yet little is known—especially for populations most at risk to vector-borne diseases (e.g., dengue, leishmaniasis, etc.). We outline several important considerations for designing epidemiological studies to encourage investigation of individual human movement, based on experience studying dengue. [ABSTRACT FROM AUTHOR]

Graph: Fig 3 Mobility values during illness (in 3-day intervals).(A) Average number of locations visited per 3-day period. Reference 1 Schaber KL, Paz-Soldan VA, Morrison AC, Elson WHD, Rothman AL, Mores CN, et al. (2019) Dengue illness impacts daily human mobility patterns in Iquitos, Peru. [Extracted from the article]