Publications by authors named "Thomas W Scott"

172 Publications

Rapid evolution of knockdown resistance haplotypes in response to pyrethroid selection in .

Evol Appl 2021 Aug 9;14(8):2098-2113. Epub 2021 Jul 9.

Genetic Engineering and Society Center North Carolina State University Raleigh NC USA.

This study describes the evolution of haplotypes in in response to pyrethroid insecticide use over the course of 18 years in Iquitos, Peru. Based on the duration and intensiveness of sampling (~10,000 samples), this is the most thorough study of population genetics in .  to date within a city. We provide evidence for the direct connection between programmatic citywide pyrethroid spraying and the increase in frequency of specific haplotypes by identifying two evolutionary events in the population. The relatively high selection coefficients, even under infrequent insecticide pressure, emphasize how quickly .  populations can evolve. In our examination of the literature on mosquitoes and other insect pests, we could find no cases where a pest evolved so quickly to so few exposures to low or nonresidual insecticide applications. The observed rapid increase in frequency of resistance alleles might have been aided by the incomplete dominance of resistance-conferring alleles over corresponding susceptibility alleles. In addition to dramatic temporal shifts, spatial suppression experiments reveal that genetic heterogeneity existed not only at the citywide scale, but also on a very fine scale within the city.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/eva.13269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372076PMC
August 2021

Pandemic-associated mobility restrictions could cause increases in dengue virus transmission.

PLoS Negl Trop Dis 2021 08 9;15(8):e0009603. Epub 2021 Aug 9.

Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, United States of America.

Background: The COVID-19 pandemic has induced unprecedented reductions in human mobility and social contacts throughout the world. Because dengue virus (DENV) transmission is strongly driven by human mobility, behavioral changes associated with the pandemic have been hypothesized to impact dengue incidence. By discouraging human contact, COVID-19 control measures have also disrupted dengue vector control interventions, the most effective of which require entry into homes. We sought to investigate how and why dengue incidence could differ under a lockdown scenario with a proportion of the population sheltered at home.

Methodology & Principal Findings: We used an agent-based model with a realistic treatment of human mobility and vector control. We found that a lockdown in which 70% of the population sheltered at home and which occurred in a season when a new serotype invaded could lead to a small average increase in cumulative DENV infections of up to 10%, depending on the time of year lockdown occurred. Lockdown had a more pronounced effect on the spatial distribution of DENV infections, with higher incidence under lockdown in regions with higher mosquito abundance. Transmission was also more focused in homes following lockdown. The proportion of people infected in their own home rose from 54% under normal conditions to 66% under lockdown, and the household secondary attack rate rose from 0.109 to 0.128, a 17% increase. When we considered that lockdown measures could disrupt regular, city-wide vector control campaigns, the increase in incidence was more pronounced than with lockdown alone, especially if lockdown occurred at the optimal time for vector control.

Conclusions & Significance: Our results indicate that an unintended outcome of lockdown measures may be to adversely alter the epidemiology of dengue. This observation has important implications for an improved understanding of dengue epidemiology and effective application of dengue vector control. When coordinating public health responses during a syndemic, it is important to monitor multiple infections and understand that an intervention against one disease may exacerbate another.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pntd.0009603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375978PMC
August 2021

The impact of dengue illness on social distancing and caregiving behavior.

PLoS Negl Trop Dis 2021 Jul 19;15(7):e0009614. Epub 2021 Jul 19.

Department of Global Community Health and Behavioral Sciences, Tulane School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States of America.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pntd.0009614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354465PMC
July 2021

Disease-driven reduction in human mobility influences human-mosquito contacts and dengue transmission dynamics.

PLoS Comput Biol 2021 01 19;17(1):e1008627. Epub 2021 Jan 19.

Program of Population Biology, Ecology and Evolution, Emory University, Atlanta, Georgia, United States of America.

Heterogeneous exposure to mosquitoes determines an individual's contribution to vector-borne pathogen transmission. Particularly for dengue virus (DENV), there is a major difficulty in quantifying human-vector contacts due to the unknown coupled effect of key heterogeneities. To test the hypothesis that the reduction of human out-of-home mobility due to dengue illness will significantly influence population-level dynamics and the structure of DENV transmission chains, we extended an existing modeling framework to include social structure, disease-driven mobility reductions, and heterogeneous transmissibility from different infectious groups. Compared to a baseline model, naïve to human pre-symptomatic infectiousness and disease-driven mobility changes, a model including both parameters predicted an increase of 37% in the probability of a DENV outbreak occurring; a model including mobility change alone predicted a 15.5% increase compared to the baseline model. At the individual level, models including mobility change led to a reduction of the importance of out-of-home onward transmission (R, the fraction of secondary cases predicted to be generated by an individual) by symptomatic individuals (up to -62%) at the expense of an increase in the relevance of their home (up to +40%). An individual's positive contribution to R could be predicted by a GAM including a non-linear interaction between an individual's biting suitability and the number of mosquitoes in their home (>10 mosquitoes and 0.6 individual attractiveness significantly increased R). We conclude that the complex fabric of social relationships and differential behavioral response to dengue illness cause the fraction of symptomatic DENV infections to concentrate transmission in specific locations, whereas asymptomatic carriers (including individuals in their pre-symptomatic period) move the virus throughout the landscape. Our findings point to the difficulty of focusing vector control interventions reactively on the home of symptomatic individuals, as this approach will fail to contain virus propagation by visitors to their house and asymptomatic carriers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pcbi.1008627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845972PMC
January 2021

Heterogeneity of Dengue Illness in Community-Based Prospective Study, Iquitos, Peru.

Emerg Infect Dis 2020 09;26(9):2077-2086

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3201/eid2609.191472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454099PMC
September 2020

Measuring health related quality of life for dengue patients in Iquitos, Peru.

PLoS Negl Trop Dis 2020 07 28;14(7):e0008477. Epub 2020 Jul 28.

Department of Global Community Health and Behavioral Sciences, Tulane School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States of America.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pntd.0008477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413550PMC
July 2020

Vector bionomics and vectorial capacity as emergent properties of mosquito behaviors and ecology.

PLoS Comput Biol 2020 04 22;16(4):e1007446. Epub 2020 Apr 22.

Institute for Health Metrics and Evaluation, University of Washington, Seattle, Washington, United States of America.

Mosquitoes are important vectors for pathogens that infect humans and other vertebrate animals. Some aspects of adult mosquito behavior and mosquito ecology play an important role in determining the capacity of vector populations to transmit pathogens. Here, we re-examine factors affecting the transmission of pathogens by mosquitoes using a new approach. Unlike most previous models, this framework considers the behavioral states and state transitions of adult mosquitoes through a sequence of activity bouts. We developed a new framework for individual-based simulation models called MBITES (Mosquito Bout-based and Individual-based Transmission Ecology Simulator). In MBITES, it is possible to build models that simulate the behavior and ecology of adult mosquitoes in exquisite detail on complex resource landscapes generated by spatial point processes. We also developed an ordinary differential equation model which is the Kolmogorov forward equations for models developed in MBITES under a specific set of simplifying assumptions. While mosquito infection and pathogen development are one possible part of a mosquito's state, that is not our main focus. Using extensive simulation using some models developed in MBITES, we show that vectorial capacity can be understood as an emergent property of simple behavioral algorithms interacting with complex resource landscapes, and that relative density or sparsity of resources and the need to search can have profound consequences for mosquito populations' capacity to transmit pathogens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pcbi.1007446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197866PMC
April 2020

Optimizing the deployment of ultra-low volume and targeted indoor residual spraying for dengue outbreak response.

PLoS Comput Biol 2020 04 20;16(4):e1007743. Epub 2020 Apr 20.

Department of Biological Sciences & Eck Institute of Global Health, University of Notre Dame, Notre Dame, Indiana, United States of America.

Recent years have seen rising incidence of dengue and large outbreaks of Zika and chikungunya, which are all caused by viruses transmitted by Aedes aegypti mosquitoes. In most settings, the primary intervention against Aedes-transmitted viruses is vector control, such as indoor, ultra-low volume (ULV) spraying. Targeted indoor residual spraying (TIRS) has the potential to more effectively impact Aedes-borne diseases, but its implementation requires careful planning and evaluation. The optimal time to deploy these interventions and their relative epidemiological effects are, however, not well understood. We used an agent-based model of dengue virus transmission calibrated to data from Iquitos, Peru to assess the epidemiological effects of these interventions under differing strategies for deploying them. Specifically, we compared strategies where spray application was initiated when incidence rose above a threshold based on incidence in recent years to strategies where spraying occurred at the same time(s) each year. In the absence of spraying, the model predicted 361,000 infections [inter-quartile range (IQR): 347,000-383,000] in the period 2000-2010. The ULV strategy with the fewest median infections was spraying twice yearly, in March and October, which led to a median of 172,000 infections [IQR: 158,000-183,000], a 52% reduction from baseline. Compared to spraying once yearly in September, the best threshold-based strategy utilizing ULV had fewer median infections (254,000 vs. 261,000), but required more spraying (351 vs. 274 days). For TIRS, the best strategy was threshold-based, which led to the fewest infections of all strategies tested (9,900; [IQR: 8,720-11,400], a 94% reduction), and required fewer days spraying than the equivalent ULV strategy (280). Although spraying twice each year is likely to avert the most infections, our results indicate that a threshold-based strategy can become an alternative to better balance the translation of spraying effort into impact, particularly if used with a residual insecticide.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pcbi.1007743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200023PMC
April 2020

The impact of insecticide treated curtains on dengue virus transmission: A cluster randomized trial in Iquitos, Peru.

PLoS Negl Trop Dis 2020 04 10;14(4):e0008097. Epub 2020 Apr 10.

Vector Biology Department, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.

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 cluster randomized trials for vector control interventions against Aedes-transmitted virus infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pntd.0008097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176142PMC
April 2020

The importance of vector control for the control and elimination of vector-borne diseases.

PLoS Negl Trop Dis 2020 01 16;14(1):e0007831. Epub 2020 Jan 16.

Department of Biosciences, Durham University, Durham, United Kingdom.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pntd.0007831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964823PMC
January 2020

Adaptation is maintained by the parliament of genes.

Nat Commun 2019 11 14;10(1):5163. Epub 2019 Nov 14.

Department of Zoology, University of Oxford, Zoology Research and Administration Building, 11a Mansfield Road, Oxford, OX1 3SZ, UK.

Fields such as behavioural and evolutionary ecology are built on the assumption that natural selection leads to organisms that behave as if they are trying to maximise their fitness. However, there is considerable evidence for selfish genetic elements that change the behaviour of individuals to increase their own transmission. How can we reconcile this contradiction? Here we show that: (1) when selfish genetic elements have a greater impact at the individual level, they are more likely to be suppressed, and suppression spreads more quickly; (2) selection on selfish genetic elements leads them towards a greater impact at the individual level, making them more likely to be suppressed; (3) the majority interest within the genome generally prevails over 'cabals' of a few genes, irrespective of genome size, mutation rate and the sophistication of trait distorters. Overall, our results suggest that even when there is the potential for considerable genetic conflict, this will often have negligible impact at the individual level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-019-13169-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856117PMC
November 2019

Dengue illness impacts daily human mobility patterns in Iquitos, Peru.

PLoS Negl Trop Dis 2019 09 23;13(9):e0007756. Epub 2019 Sep 23.

Program of Population Biology, Ecology and Evolution, Emory University, Atlanta, Georgia, United States of America.

Background: Human mobility plays a central role in shaping pathogen transmission by generating spatial and/or individual variability in potential pathogen-transmitting contacts. Recent research has shown that symptomatic infection can influence human mobility and pathogen transmission dynamics. Better understanding the complex relationship between symptom severity, infectiousness, and human mobility requires quantification of movement patterns throughout infectiousness. For dengue virus (DENV), human infectiousness peaks 0-2 days after symptom onset, making it paramount to understand human movement patterns from the beginning of illness.

Methodology And Principal Findings: Through community-based febrile surveillance and RT-PCR assays, we identified a cohort of DENV+ residents of the city of Iquitos, Peru (n = 63). Using retrospective interviews, we measured the movements of these individuals when healthy and during each day of symptomatic illness. The most dramatic changes in mobility occurred during the first three days after symptom onset; individuals visited significantly fewer locations (Wilcoxon test, p = 0.017) and spent significantly more time at home (Wilcoxon test, p = 0.005), compared to when healthy. By 7-9 days after symptom onset, mobility measures had returned to healthy levels. Throughout an individual's symptomatic period, the day of illness and their subjective sense of well-being were the most significant predictors for the number of locations and houses they visited.

Conclusions/significance: Our study is one of the first to collect and analyze human mobility data at a daily scale during symptomatic infection. Accounting for the observed changes in human mobility throughout illness will improve understanding of the impact of disease on DENV transmission dynamics and the interpretation of public health-based surveillance data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pntd.0007756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776364PMC
September 2019

The genetic structure of Aedes aegypti populations is driven by boat traffic in the Peruvian Amazon.

PLoS Negl Trop Dis 2019 09 18;13(9):e0007552. Epub 2019 Sep 18.

Department of Entomology and Nematology, University of California, Davis, California, United States of America.

In the Americas, as in much of the rest of the world, the dengue virus vector Aedes aegypti is found in close association with human habitations, often leading to high population densities of mosquitoes in urban settings. In the Peruvian Amazon, this vector has been expanding to rural communities over the last 10-15 years, but to date, the population genetic structure of Ae. aegypti in this region has not been characterized. To investigate the relationship between Ae. aegypti gene flow and human transportation networks, we characterized mosquito population structure using a panel of 8 microsatellite markers and linked results to various potential mechanisms for long-distance dispersal. Adult and immature Ae. aegypti (>20 individuals per site) were collected from Iquitos city and from six neighboring riverine communities, i.e., Nauta, Indiana, Mazan, Barrio Florida, Tamshiaco, and Aucayo. FST statistics indicate significant, but low to moderate differentiation for the majority of study site pairs. Population structure of Ae. aegypti is not correlated with the geographic distance between towns, suggesting that human transportation networks provide a reasonable explanation for the high levels of population mixing. Our results indicate that Ae. aegypti gene flow among sub-populations is greatest between locations with heavy boat traffic, such as Iquitos-Tamshiaco and Iquitos-Indiana-Mazan, and lowest between locations with little or no boat/road traffic between them such as Barrio Florida-Iquitos. Bayesian clustering analysis showed ancestral admixture among three genetic clusters; no single cluster was exclusive to any site. Our results are consistent with the hypothesis that human transportation networks, particularly riverways, are responsible for the geographic spread of Ae. aegypti in the Peruvian Amazon. Our findings are applicable to other regions of the world characterized by networks of urban islands connected by fluvial transport routes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pntd.0007552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6750575PMC
September 2019

Model-based assessment of public health impact and cost-effectiveness of dengue vaccination following screening for prior exposure.

PLoS Negl Trop Dis 2019 07 1;13(7):e0007482. Epub 2019 Jul 1.

Department of Biological Sciences and Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN, United States of America.

The tetravalent dengue vaccine CYD-TDV (Dengvaxia) is the first licensed vaccine against dengue, but recent findings indicate an elevated risk of severe disease among vaccinees without prior dengue virus (DENV) exposure. The World Health Organization currently recommends CYD-TDV only for individuals with serological confirmation of past DENV exposure. Our objective was to evaluate the potential health impact and cost-effectiveness of vaccination following serological screening. To do so, we used an agent-based model to simulate DENV transmission with and without vaccination over a 10-year timeframe. Across a range of values for the proportion of vaccinees with prior DENV exposure, we projected the proportion of symptomatic and hospitalized cases averted as a function of the sensitivity and specificity of serological screening. Scenarios about the cost-effectiveness of screening and vaccination were chosen to be representative of Brazil and the Philippines. We found that public health impact depended primarily on sensitivity in high-transmission settings and on specificity in low-transmission settings. Cost-effectiveness could be achievable from the perspective of a public payer provided that sensitivity and the value of a disability-adjusted life-year were both high, but only in high-transmission settings. Requirements for reducing relative risk and achieving cost-effectiveness from an individual perspective were more restricted, due to the fact that those who test negative pay for screening but receive no benefit. Our results predict that cost-effectiveness could be achieved only in high-transmission areas of dengue-endemic countries with a relatively high per capita GDP, such as Panamá (13,680 USD), Brazil (8,649 USD), México (8,201 USD), or Thailand (5,807 USD). In conclusion, vaccination with CYD-TDV following serological screening could have a positive impact in some high-transmission settings, provided that screening is highly specific (to minimize individual harm), at least moderately sensitive (to maximize population benefit), and sufficiently inexpensive (depending on the setting).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pntd.0007482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625736PMC
July 2019

The current and future global distribution and population at risk of dengue.

Nat Microbiol 2019 09 10;4(9):1508-1515. Epub 2019 Jun 10.

Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA.

Dengue is a mosquito-borne viral infection that has spread throughout the tropical world over the past 60 years and now affects over half the world's population. The geographical range of dengue is expected to further expand due to ongoing global phenomena including climate change and urbanization. We applied statistical mapping techniques to the most extensive database of case locations to date to predict global environmental suitability for the virus as of 2015. We then made use of climate, population and socioeconomic projections for the years 2020, 2050 and 2080 to project future changes in virus suitability and human population at risk. This study is the first to consider the spread of Aedes mosquito vectors to project dengue suitability. Our projections provide a key missing piece of evidence for the changing global threat of vector-borne disease and will help decision-makers worldwide to better prepare for and respond to future changes in dengue risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41564-019-0476-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784886PMC
September 2019

Estimating the impact of city-wide Aedes aegypti population control: An observational study in Iquitos, Peru.

PLoS Negl Trop Dis 2019 05 30;13(5):e0007255. Epub 2019 May 30.

Fogarty International Center, National Institutes of Health, Bethesda, MD, United States of America.

During the last 50 years, the geographic range of the mosquito Aedes aegypti has increased dramatically, in parallel with a sharp increase in the disease burden from the viruses it transmits, including Zika, chikungunya, and dengue. There is a growing consensus that vector control is essential to prevent Aedes-borne diseases, even as effective vaccines become available. What remains unclear is how effective vector control is across broad operational scales because the data and the analytical tools necessary to isolate the effect of vector-oriented interventions have not been available. We developed a statistical framework to model Ae. aegypti abundance over space and time and applied it to explore the impact of citywide vector control conducted by the Ministry of Health (MoH) in Iquitos, Peru, over a 12-year period. Citywide interventions involved multiple rounds of intradomicile insecticide space spray over large portions of urban Iquitos (up to 40% of all residences) in response to dengue outbreaks. Our model captured significant levels of spatial, temporal, and spatio-temporal variation in Ae. aegypti abundance within and between years and across the city. We estimated the shape of the relationship between the coverage of neighborhood-level vector control and reductions in female Ae. aegypti abundance; i.e., the dose-response curve. The dose-response curve, with its associated uncertainties, can be used to gauge the necessary spraying effort required to achieve a desired effect and is a critical tool currently absent from vector control programs. We found that with complete neighborhood coverage MoH intra-domicile space spray would decrease Ae. aegypti abundance on average by 67% in the treated neighborhood. Our framework can be directly translated to other interventions in other locations with geolocated mosquito abundance data. Results from our analysis can be used to inform future vector-control applications in Ae. aegypti endemic areas globally.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pntd.0007255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542505PMC
May 2019

Publisher Correction: Past and future spread of the arbovirus vectors Aedes aegypti and Aedes albopictus.

Nat Microbiol 2019 May;4(5):901

Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA.

This Article was mistakenly not made Open Access when originally published; this has now been amended, and information about the Creative Commons Attribution 4.0 International License has been added into the 'Additional information' section.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41564-019-0440-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609323PMC
May 2019

Publisher Correction: Past and future spread of the arbovirus vectors Aedes aegypti and Aedes albopictus.

Nat Microbiol 2019 May;4(5):900

Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA.

In the version of this Article originally published, the affiliation for author Catherine Linard was incorrectly stated as 'Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK'. The correct affiliation is 'Spatial Epidemiology Lab (SpELL), Universite Libre de Bruxelles, Brussels, Belgium'. The affiliation for author Hongjie Yu was also incorrectly stated as 'Department of Statistics, Harvard University, Cambridge, MA, USA'. The correct affiliation is 'School of Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China'. This has now been amended in all versions of the Article.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41564-019-0429-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608402PMC
May 2019

An agent-based model of dengue virus transmission shows how uncertainty about breakthrough infections influences vaccination impact projections.

PLoS Comput Biol 2019 03 20;15(3):e1006710. Epub 2019 Mar 20.

Fogarty International Center, National Institutes of Health, Bethesda, MD, United States of America.

Prophylactic vaccination is a powerful tool for reducing the burden of infectious diseases, due to a combination of direct protection of vaccinees and indirect protection of others via herd immunity. Computational models play an important role in devising strategies for vaccination by making projections of its impacts on public health. Such projections are subject to uncertainty about numerous factors, however. For example, many vaccine efficacy trials focus on measuring protection against disease rather than protection against infection, leaving the extent of breakthrough infections (i.e., disease ameliorated but infection unimpeded) among vaccinees unknown. Our goal in this study was to quantify the extent to which uncertainty about breakthrough infections results in uncertainty about vaccination impact, with a focus on vaccines for dengue. To realistically account for the many forms of heterogeneity in dengue virus (DENV) transmission, which could have implications for the dynamics of indirect protection, we used a stochastic, agent-based model for DENV transmission informed by more than a decade of empirical studies in the city of Iquitos, Peru. Following 20 years of routine vaccination of nine-year-old children at 80% coverage, projections of the proportion of disease episodes averted varied by a factor of 1.76 (95% CI: 1.54-2.06) across the range of uncertainty about breakthrough infections. This was equivalent to the range of vaccination impact projected across a range of uncertainty about vaccine efficacy of 0.268 (95% CI: 0.210-0.329). Until uncertainty about breakthrough infections can be addressed empirically, our results demonstrate the importance of accounting for it in models of vaccination impact.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pcbi.1006710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443188PMC
March 2019

Evolutionary maintenance of genomic diversity within arbuscular mycorrhizal fungi.

Ecol Evol 2019 Mar 11;9(5):2425-2435. Epub 2019 Feb 11.

Department of Zoology University of Oxford Oxford UK.

Most organisms are built from a single genome. In striking contrast, arbuscular mycorrhizal fungi appear to maintain genomic variation within an individual fungal network. Arbuscular mycorrhizal fungi dwell in the soil, form mutualistic networks with plants, and bear multiple, potentially genetically diverse nuclei within a network. We explore, from a theoretical perspective, why such genetic diversity might be maintained within individuals. We consider selection acting within and between individual fungal networks. We show that genetic diversity could provide a benefit at the level of the individual, by improving growth in variable environments, and that this can stabilize genetic diversity even in the presence of nuclear conflict. Arbuscular mycorrhizal fungi complicate our understanding of organismality, but our findings offer a way of understanding such biological anomalies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ece3.4834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405528PMC
March 2019

Past and future spread of the arbovirus vectors Aedes aegypti and Aedes albopictus.

Nat Microbiol 2019 05 4;4(5):854-863. Epub 2019 Mar 4.

Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA.

The global population at risk from mosquito-borne diseases-including dengue, yellow fever, chikungunya and Zika-is expanding in concert with changes in the distribution of two key vectors: Aedes aegypti and Aedes albopictus. The distribution of these species is largely driven by both human movement and the presence of suitable climate. Using statistical mapping techniques, we show that human movement patterns explain the spread of both species in Europe and the United States following their introduction. We find that the spread of Ae. aegypti is characterized by long distance importations, while Ae. albopictus has expanded more along the fringes of its distribution. We describe these processes and predict the future distributions of both species in response to accelerating urbanization, connectivity and climate change. Global surveillance and control efforts that aim to mitigate the spread of chikungunya, dengue, yellow fever and Zika viruses must consider the so far unabated spread of these mosquitos. Our maps and predictions offer an opportunity to strategically target surveillance and control programmes and thereby augment efforts to reduce arbovirus burden in human populations globally.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41564-019-0376-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522366PMC
May 2019

Feasibility of feeding Aedes aegypti mosquitoes on dengue virus-infected human volunteers for vector competence studies in Iquitos, Peru.

PLoS Negl Trop Dis 2019 02 12;13(2):e0007116. Epub 2019 Feb 12.

Department of Entomology and Nematology, University of California, Davis, Davis, California, United States of America.

Background: Transmission of dengue virus (DENV) from humans to mosquitoes represents a critical component of dengue epidemiology. Examinations of this process have generally been hampered by a lack of methods that adequately represent natural acquisition of DENV by mosquitoes from humans. In this study, we assessed artificial and natural blood feeding methods based on rates of DENV infection and dissemination within mosquitoes for use in a field-based epidemiological cohort study in Iquitos, Peru.

Methodology/principal Findings: Our study was implemented, stepwise, between 2011 and 2015. Participants who were 5 years and older with 5 or fewer days of fever were enrolled from ongoing clinic- and neighborhood-based studies on dengue in Iquitos. Wild type, laboratory-reared Aedes aegypti were fed directly on febrile individuals or on blood collected from participants that was either untreated or treated with EDTA. Mosquitoes were tested after approximately 14 days of extrinsic incubation for DENV infection and dissemination. A total of 58 participants, with viremias ranging from 1.3 × 10(2) to 2.9 × 10(6) focus-forming units per mL of serum, participated in one or more feeding methods. DENV infection and dissemination rates were not significantly different following direct and indirect-EDTA feeding; however, they were significantly lower for mosquitoes that fed indirectly on blood with no additive. Relative to direct feeding, infection rates showed greater variation following indirect-EDTA than indirect-no additive feeding. Dissemination rates were similar across all feeding methods. No differences were detected in DENV infection or dissemination rates in mosquitoes fed directly on participants with different dengue illness severity.

Conclusions/significance: Our study demonstrates the feasibility of using direct and indirect feeding methods for field-based studies on vector competence. Direct mosquito feeding is preferable in terms of logistical ease, biosecurity, and reliability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pntd.0007116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388938PMC
February 2019

Acceptability of Aedes aegypti blood feeding on dengue virus-infected human volunteers for vector competence studies in Iquitos, Peru.

PLoS Negl Trop Dis 2019 02 11;13(2):e0007090. Epub 2019 Feb 11.

Global Community Health and Behavioral Sciences, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States of America.

As part of a study to investigate drivers of dengue virus (DENV) transmission dynamics, this qualitative study explored whether DENV-infected residents of Iquitos, Peru, considered it acceptable (1) to participate in direct mosquito feeding experiments (lab-reared Aedes aegypti mosquitoes fed directly on human volunteers) and (2) to provide blood meals indirectly (Ae. aegypti fed on blood drawn from participants by venipuncture). Twelve focus group discussions (FGDs; 94 participants: 82 females and 12 males) were conducted in January 2014 to explore six themes: (1) concerns and preferences regarding direct mosquito feeds and blood draws, (2) comprehension of and misconceptions about study procedures, (3) motivating factors for participation, (4) acceptability of children's participation, (5) willingness to provide multiple samples over several days, and (6) preference for direct feedings in homes versus the study laboratory. Results of FGDs, including one with 5 of 53 past direct mosquito feed participants, indicated that mosquito feeding procedures are acceptable to Iquitos residents when they are provided with information and a few key messages are properly reinforced. FGD participants' concerns focused primarily on safety issues rather than discomfort associated with mosquito bites. A video explaining the study dramatically increased comprehension of the study procedures. The majority of participants expressed a preference for mosquito feeding over venipuncture. Adults supported child participation if the children themselves assented. For most participants, home feedings were preferred over those in a laboratory. A major impetus for participation was the idea that results would contribute to an improved understanding of DENV transmission in Iquitos. Findings from our study will support future large-scale studies that employ direct mosquito feeding, a low-risk, non-invasive procedure that is experimentally superior to artificial mosquito feeding methods.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pntd.0007090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386403PMC
February 2019

Biased efficacy estimates in phase-III dengue vaccine trials due to heterogeneous exposure and differential detectability of primary infections across trial arms.

PLoS One 2019 25;14(1):e0210041. Epub 2019 Jan 25.

Department of Biological Sciences and Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN, United States of America.

Vaccine efficacy (VE) estimates are crucial for assessing the suitability of dengue vaccine candidates for public health implementation, but efficacy trials are subject to a known bias to estimate VE toward the null if heterogeneous exposure is not accounted for in the analysis of trial data. In light of many well-characterized sources of heterogeneity in dengue virus (DENV) transmission, our goal was to estimate the potential magnitude of this bias in VE estimates for a hypothetical dengue vaccine. To ensure that we realistically modeled heterogeneous exposure, we simulated city-wide DENV transmission and vaccine trial protocols using an agent-based model calibrated with entomological and epidemiological data from long-term field studies in Iquitos, Peru. By simulating a vaccine with a true VE of 0.8 in 1,000 replicate trials each designed to attain 90% power, we found that conventional methods underestimated VE by as much as 21% due to heterogeneous exposure. Accounting for the number of exposures in the vaccine and placebo arms eliminated this bias completely, and the more realistic option of including a frailty term to model exposure as a random effect reduced this bias partially. We also discovered a distinct bias in VE estimates away from the null due to lower detectability of primary DENV infections among seronegative individuals in the vaccinated group. This difference in detectability resulted from our assumption that primary infections in vaccinees who are seronegative at baseline resemble secondary infections, which experience a shorter window of detectable viremia due to a quicker immune response. This resulted in an artefactual finding that VE estimates for the seronegative group were approximately 1% greater than for the seropositive group. Simulation models of vaccine trials that account for these factors can be used to anticipate the extent of bias in field trials and to aid in their interpretation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210041PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347271PMC
September 2019

Integrated Aedes management for the control of Aedes-borne diseases.

PLoS Negl Trop Dis 2018 12 6;12(12):e0006845. Epub 2018 Dec 6.

MIVEGEC, IRD, CNRS, University of Montpellier, Montpellier, France.

Background: Diseases caused by Aedes-borne viruses, such as dengue, Zika, chikungunya, and yellow fever, are emerging and reemerging globally. The causes are multifactorial and include global trade, international travel, urbanisation, water storage practices, lack of resources for intervention, and an inadequate evidence base for the public health impact of Aedes control tools. National authorities need comprehensive evidence-based guidance on how and when to implement Aedes control measures tailored to local entomological and epidemiological conditions.

Methods And Findings: This review is one of a series being conducted by the Worldwide Insecticide resistance Network (WIN). It describes a framework for implementing Integrated Aedes Management (IAM) to improve control of diseases caused by Aedes-borne viruses based on available evidence. IAM consists of a portfolio of operational actions and priorities for the control of Aedes-borne viruses that are tailored to different epidemiological and entomological risk scenarios. The framework has 4 activity pillars: (i) integrated vector and disease surveillance, (ii) vector control, (iii) community mobilisation, and (iv) intra- and intersectoral collaboration as well as 4 supporting activities: (i) capacity building, (ii) research, (iii) advocacy, and (iv) policies and laws.

Conclusions: IAM supports implementation of the World Health Organisation Global Vector Control Response (WHO GVCR) and provides a comprehensive framework for health authorities to devise and deliver sustainable, effective, integrated, community-based, locally adapted vector control strategies in order to reduce the burden of Aedes-transmitted arboviruses. The success of IAM requires strong commitment and leadership from governments to maintain proactive disease prevention programs and preparedness for rapid responses to outbreaks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pntd.0006845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283470PMC
December 2018

Contributions from the silent majority dominate dengue virus transmission.

PLoS Pathog 2018 05 3;14(5):e1006965. Epub 2018 May 3.

Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN, United States.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.ppat.1006965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933708PMC
May 2018

Efficacy of Aedes aegypti control by indoor Ultra Low Volume (ULV) insecticide spraying in Iquitos, Peru.

PLoS Negl Trop Dis 2018 Apr 6;12(4):e0006378. Epub 2018 Apr 6.

Naval Medical Research Unit No. 6, 3230 Lima Pl., Washington DC, Lima and Iquitos, Peru.

Background: Aedes aegypti is a primary vector of dengue, chikungunya, Zika, and urban yellow fever viruses. Indoor, ultra low volume (ULV) space spraying with pyrethroid insecticides is the main approach used for Ae. aegypti emergency control in many countries. Given the widespread use of this method, the lack of large-scale experiments or detailed evaluations of municipal spray programs is problematic.

Methodology/principal Findings: Two experimental evaluations of non-residual, indoor ULV pyrethroid spraying were conducted in Iquitos, Peru. In each, a central sprayed sector was surrounded by an unsprayed buffer sector. In 2013, spray and buffer sectors included 398 and 765 houses, respectively. Spraying reduced the mean number of adults captured per house by ~83 percent relative to the pre-spray baseline survey. In the 2014 experiment, sprayed and buffer sectors included 1,117 and 1,049 houses, respectively. Here, the sprayed sector's number of adults per house was reduced ~64 percent relative to baseline. Parity surveys in the sprayed sector during the 2014 spray period indicated an increase in the proportion of very young females. We also evaluated impacts of a 2014 citywide spray program by the local Ministry of Health, which reduced adult populations by ~60 percent. In all cases, adult densities returned to near-baseline levels within one month.

Conclusions/significance: Our results demonstrate that densities of adult Ae. aegypti can be reduced by experimental and municipal spraying programs. The finding that adult densities return to approximately pre-spray densities in less than a month is similar to results from previous, smaller scale experiments. Our results demonstrate that ULV spraying is best viewed as having a short-term entomological effect. The epidemiological impact of ULV spraying will need evaluation in future trials that measure capacity of insecticide spraying to reduce human infection or disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pntd.0006378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906025PMC
April 2018
-->