Publications by authors named "Gonzalo M Vázquez-Prokopec"

75 Publications

Efficacy of targeted indoor residual spraying with the pyrrole insecticide chlorfenapyr against pyrethroid-resistant Aedes aegypti.

PLoS Negl Trop Dis 2021 Oct 4;15(10):e0009822. Epub 2021 Oct 4.

Department of Environmental Sciences, Emory University, Atlanta, Georgia, United States of America.

Background: There is an increased need to mitigate the emergence of insecticide resistance and incorporate new formulations and modes of application to control the urban vector Aedes aegypti. Most research and development of insecticide formulations for the control of Ae. aegypti has focused on their peridomestic use as truck-mounted ULV-sprays or thermal fogs despite the widespread knowledge that most resting Ae. aegypti are found indoors. A recent modification of indoor residual spraying (IRS), termed targeted IRS (TIRS) works by restricting applications to 1.5 m down to the floor and on key Ae. aegypti resting sites (under furniture). TIRS also opens the possibility of evaluating novel residual insecticide formulations currently being developed for malaria IRS.

Methods: We evaluated the residual efficacy of chlorfenapyr, formulated as Sylando 240SC, for 12 months on free-flying field-derived pyrethroid-resistant Ae. aegypti using a novel experimental house design in Merida, Mexico. On a monthly basis, 600 female Ae. aegypti were released into the houses and left indoors with access to sugar solution for 24 hours. After the exposure period, dead and alive mosquitoes were counted in houses treated with chlorfenapyr as well as untreated control houses to calculate 24-h mortality. An evaluation for these exposed cohorts of surviving mosquitoes was extended up to seven days under laboratory conditions to quantify "delayed mortality".

Results: Mean acute (24-h) mortality of pyrethroid-resistant Ae. aegypti ranged 80-97% over 5 months, dropping below 30% after 7 months post-TIRS. If delayed mortality was considered (quantifying mosquito mortality up to 7 days after exposure), residual efficacy was above 90% for up to 7 months post-TIRS application. Generalized Additive Mixed Models quantified a residual efficacy of chlorfenapyr of 225 days (ca. 7.5 months).

Conclusions: Chlorfenapyr represents a new option for TIRS control of Ae. aegypti in urban areas, providing a highly-effective time of protection against indoor Ae. aegypti females of up to 7 months.
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http://dx.doi.org/10.1371/journal.pntd.0009822DOI Listing
October 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.
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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.
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http://dx.doi.org/10.1371/journal.pntd.0009614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354465PMC
July 2021

Identifying urban hotspots of dengue, chikungunya, and Zika transmission in Mexico to support risk stratification efforts: a spatial analysis.

Lancet Planet Health 2021 05;5(5):e277-e285

Department of Environmental Sciences, Emory University, Atlanta, GA, USA. Electronic address:

Background: Effective Aedes aegypti control is limited, in part, by the difficulty in achieving sufficient intervention coverage. To maximise the effect of vector control, areas with persistently high numbers of Aedes-borne disease cases could be identified and prioritised for preventive interventions. We aimed to identify persistent Aedes-borne disease hotspots in cities across southern Mexico.

Methods: In this spatial analysis, geocoded cases of dengue, chikungunya, and Zika from nine endemic Mexican cities were aggregated at the census-tract level. We included cities that were located in southern Mexico (the arbovirus endemic region of Mexico), with a high burden of dengue cases (ie, more than 5000 cases reported during a 10-year period), and listed as high priority for the Mexican dengue control and prevention programme. The Getis-Ord Gi*(d) statistic was applied to yearly slices of the dataset to identify spatial hotspots of each disease in each city. We used Kendall's W coefficient to quantify the agreement in the distribution of each virus.

Findings: 128 507 dengue, 4752 chikungunya and 25 755 Zika clinical cases were reported between Jan 1, 2008, and Dec 31, 2016. All cities showed evidence of transmission heterogeneity, with a mean of 17·6% (SD 4·7) of their total area identified as persistent disease hotspots. Hotspots accounted for 25·6% (SD 9·7; range 12·8-43·0) of the population and 32·1% (10·5; 19·6-50·5) of all Aedes-borne disease cases reported. We found an overlap between hotspots of 61·7% for dengue and Zika and 53·3% for dengue and chikungunya. Dengue hotspots in 2008-16 were significantly associated with dengue hotspots detected during 2017-20 in five of the nine cities. Heads of vector control confirmed hotspot areas as problem zones for arbovirus transmission.

Interpretation: This study provides evidence of the overlap of Aedes-borne diseases within geographical hotspots and a methodological framework for the stratification of arbovirus transmission risk within urban areas, which can guide the implementation of surveillance and vector control.

Funding: USAID, the US Centers for Disease Control and Prevention, the Canadian Institutes of Health Research, International Development Research Centre, Fondo Mixto CONACyT (Mexico)-Gobierno del Estado de Yucatan, and the US National Institutes of Health.

Translation: For the Spanish translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S2542-5196(21)00030-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114339PMC
May 2021

The entomological impact of passive metofluthrin emanators against indoor Aedes aegypti: A randomized field trial.

PLoS Negl Trop Dis 2021 01 26;15(1):e0009036. Epub 2021 Jan 26.

Unidad Colaborativa de Bioensayos Entomológicos, Campus de Ciencias. Biológicas y Agropecuarias, Universidad Autónoma de Yucatán, Mérida, Yucatán, México.

Background: In the absence of vaccines or drugs, insecticides are the mainstay of Aedes-borne disease control. Their utility is challenged by the slow deployment of resources, poor community compliance and inadequate household coverage. Novel application methods are required.

Methodology And Principal Findings: A 10% w/w metofluthrin "emanator" that passively disseminates insecticide from an impregnated net was evaluated in a randomized trial of 200 houses in Mexico. The devices were introduced at a rate of 1 per room and replaced at 3-week intervals. During each of 7 consecutive deployment cycles, indoor resting mosquitoes were sampled using aspirator collections. Assessments of mosquito landing behaviours were made in a subset of houses. Pre-treatment, there were no differences in Aedes aegypti indices between houses recruited to the control and treatment arms. Immediately after metofluthrin deployment, the entomological indices between the trial arms diverged. Averaged across the trial, there were significant reductions in Abundance Rate Ratios for total Ae. aegypti, female abundance and females that contained blood meals (2.5, 2.4 and 2.3-times fewer mosquitoes respectively; P<0.001). Average efficacy was 60.2% for total adults, 58.3% for females, and 57.2% for blood-fed females. The emanators also reduced mosquito landings by 90% from 12.5 to 1.2 per 10-minute sampling period (P<0.05). Homozygous forms of the pyrethroid resistant kdr alleles V410L, V1016L and F1534C were common in the target mosquito population; found in 39%, 24% and 95% of mosquitoes collected during the trial.

Conclusions/significance: This is the first randomized control trial to evaluate the entomological impact of any volatile pyrethroid on urban Ae. aegypti. It demonstrates that volatile pyrethroids can have a sustained impact on Ae. aegypti population densities and human-vector contact indoors. These effects occur despite the presence of pyrethroid-resistant alleles in the target population. Formulations like these may have considerable utility for public health vector control responses.
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http://dx.doi.org/10.1371/journal.pntd.0009036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864418PMC
January 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.
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http://dx.doi.org/10.1371/journal.pcbi.1008627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845972PMC
January 2021

Natural arbovirus infection rate and detectability of indoor female Aedes aegypti from Mérida, Yucatán, Mexico.

PLoS Negl Trop Dis 2021 01 4;15(1):e0008972. Epub 2021 Jan 4.

Department of Environmental Sciences, Emory University, Atlanta, Georgia, United States of America.

Arbovirus infection in Aedes aegypti has historically been quantified from a sample of the adult population by pooling collected mosquitoes to increase detectability. However, there is a significant knowledge gap about the magnitude of natural arbovirus infection within areas of active transmission, as well as the sensitivity of detection of such an approach. We used indoor Ae. aegypti sequential sampling with Prokopack aspirators to collect all mosquitoes inside 200 houses with suspected active ABV transmission from the city of Mérida, Mexico, and tested all collected specimens by RT-PCR to quantify: a) the absolute arbovirus infection rate in individually tested Ae. aegypti females; b) the sensitivity of using Prokopack aspirators in detecting ABV-infected mosquitoes; and c) the sensitivity of entomological inoculation rate (EIR) and vectorial capacity (VC), two measures ABV transmission potential, to different estimates of indoor Ae. aegypti abundance. The total number of Ae. aegypti (total catch, the sum of all Ae. aegypti across all collection intervals) as well as the number on the first 10-min of collection (sample, equivalent to a routine adult aspiration session) were calculated. We individually tested by RT-PCR 2,161 Aedes aegypti females and found that 7.7% of them were positive to any ABV. Most infections were CHIKV (77.7%), followed by DENV (11.4%) and ZIKV (9.0%). The distribution of infected Aedes aegypti was overdispersed; 33% houses contributed 81% of the infected mosquitoes. A significant association between ABV infection and Ae. aegypti total catch indoors was found (binomial GLMM, Odds Ratio > 1). A 10-min indoor Prokopack collection led to a low sensitivity of detecting ABV infection (16.3% for detecting infected mosquitoes and 23.4% for detecting infected houses). When averaged across all infested houses, mean EIR ranged between 0.04 and 0.06 infective bites per person per day, and mean VC was 0.6 infectious vectors generated from a population feeding on a single infected host per house/day. Both measures were significantly and positively associated with Ae. aegypti total catch indoors. Our findings provide evidence that the accurate estimation and quantification of arbovirus infection rate and transmission risk is a function of the sampling effort, the local abundance of Aedes aegypti and the intensity of arbovirus circulation.
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http://dx.doi.org/10.1371/journal.pntd.0008972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781390PMC
January 2021

The TIRS trial: protocol for a cluster randomized controlled trial assessing the efficacy of preventive targeted indoor residual spraying to reduce Aedes-borne viral illnesses in Merida, Mexico.

Trials 2020 Oct 8;21(1):839. Epub 2020 Oct 8.

Department of Environmental Sciences, Math and Science Center, Emory University, 400 Dowman Drive, 5th floor, Suite E530, Atlanta, GA, 30322, USA.

Background: Current urban vector control strategies have failed to contain dengue epidemics and to prevent the global expansion of Aedes-borne viruses (ABVs: dengue, chikungunya, Zika). Part of the challenge in sustaining effective ABV control emerges from the paucity of evidence regarding the epidemiological impact of any Aedes control method. A strategy for which there is limited epidemiological evidence is targeted indoor residual spraying (TIRS). TIRS is a modification of classic malaria indoor residual spraying that accounts for Aedes aegypti resting behavior by applying residual insecticides on exposed lower sections of walls (< 1.5 m), under furniture, and on dark surfaces.

Methods/design: We are pursuing a two-arm, parallel, unblinded, cluster randomized controlled trial to quantify the overall efficacy of TIRS in reducing the burden of laboratory-confirmed ABV clinical disease (primary endpoint). The trial will be conducted in the city of Merida, Yucatan State, Mexico (population ~ 1million), where we will prospectively follow 4600 children aged 2-15 years at enrollment, distributed in 50 clusters of 5 × 5 city blocks each. Clusters will be randomly allocated (n = 25 per arm) using covariate-constrained randomization. A "fried egg" design will be followed, in which all blocks of the 5 × 5 cluster receive the intervention, but all sampling to evaluate the epidemiological and entomological endpoints will occur in the "yolk," the center 3 × 3 city blocks of each cluster. TIRS will be implemented as a preventive application (~ 1-2 months prior to the beginning of the ABV season). Active monitoring for symptomatic ABV illness will occur through weekly household visits and enhanced surveillance. Annual sero-surveys will be performed after each transmission season and entomological evaluations of Ae. aegypti indoor abundance and ABV infection rates monthly during the period of active surveillance. Epidemiological and entomological evaluation will continue for up to three transmission seasons.

Discussion: The findings from this study will provide robust epidemiological evidence of the efficacy of TIRS in reducing ABV illness and infection. If efficacious, TIRS could drive a paradigm shift in Aedes control by considering Ae. aegypti behavior to guide residual insecticide applications and changing deployment to preemptive control (rather than in response to symptomatic cases), two major enhancements to existing practice.

Trial Registration: ClinicalTrials.gov NCT04343521 . Registered on 13 April 2020. The protocol also complies with the WHO International Clinical Trials Registry Platform (ICTRP) (Additional file 1).

Primary Sponsor: National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIH/NIAID).
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http://dx.doi.org/10.1186/s13063-020-04780-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542575PMC
October 2020

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.
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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.
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http://dx.doi.org/10.1371/journal.pntd.0008477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413550PMC
July 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.
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http://dx.doi.org/10.1371/journal.pcbi.1007743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200023PMC
April 2020

Designing effective control of dengue with combined interventions.

Proc Natl Acad Sci U S A 2020 02 23;117(6):3319-3325. Epub 2020 Jan 23.

Emerging Pathogens Institute, University of Florida, Gainesville, FL 32611.

Viruses transmitted by mosquitoes, such as dengue, Zika, and chikungunya, have expanding ranges and seem unabated by current vector control programs. Effective control of these pathogens likely requires integrated approaches. We evaluated dengue management options in an endemic setting that combine novel vector control and vaccination using an agent-based model for Yucatán, Mexico, fit to 37 y of data. Our intervention models are informed by targeted indoor residual spraying (TIRS) experiments; trial outcomes and World Health Organization (WHO) testing guidance for the only licensed dengue vaccine, CYD-TDV; and preliminary results for in-development vaccines. We evaluated several implementation options, including varying coverage levels; staggered introductions; and a one-time, large-scale vaccination campaign. We found that CYD-TDV and TIRS interfere: while the combination outperforms either alone, performance is lower than estimated from their separate benefits. The conventional model hypothesized for in-development vaccines, however, performs synergistically with TIRS, amplifying effectiveness well beyond their independent impacts. If the preliminary performance by either of the in-development vaccines is upheld, a one-time, large-scale campaign followed by routine vaccination alongside aggressive new vector control could enable short-term elimination, with nearly all cases avoided for a decade despite continuous dengue reintroductions. If elimination is impracticable due to resource limitations, less ambitious implementations of this combination still produce amplified, longer-lasting effectiveness over single-approach interventions.
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http://dx.doi.org/10.1073/pnas.1903496117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022216PMC
February 2020

The basic reproductive number for disease systems with multiple coupled heterogeneities.

Math Biosci 2020 03 11;321:108294. Epub 2019 Dec 11.

Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.

In mathematical epidemiology, a well-known formula describes the impact of heterogeneity on the basic reproductive number, R, for situations in which transmission is separable and for which there is one source of variation in susceptibility and one source of variation in infectiousness. This formula is written in terms of the magnitudes of the heterogeneities, as quantified by their coefficients of variation, and the correlation between them. A natural question to ask is whether analogous results apply when there are multiple sources of variation in susceptibility and/or infectiousness. In this paper we demonstrate that with three or more coupled heterogeneities, R under separable transmission depends on details of the distribution of the heterogeneities in a way that is not seen in the well-known simpler situation. We provide explicit formulae for the cases of multivariate normal and multivariate log-normal distributions, showing that R can again be expressed in terms of the magnitudes of the heterogeneities and the pairwise correlations between them. The formulae, however, differ between the two multivariate distributions, demonstrating that no formula of this type applies generally when there are three or more coupled heterogeneities. We see that the results of the formulae are approximately equal when heterogeneities are relatively small and show that an earlier result in the literature (Koella, 1991) should be viewed in this light. We provide numerical illustrations of our results and discuss a setting in which coupled heterogeneities are likely to have a major impact on the value of R. We also describe a rather surprising result: in a system with three heterogeneities, R can exhibit non-monotonic behavior with increasing levels of heterogeneity, in marked contrast to the familiar two heterogeneity setting in which R either increases or decreases with increasing heterogeneity.
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http://dx.doi.org/10.1016/j.mbs.2019.108294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905963PMC
March 2020

Predicting the success of an invader: Niche shift versus niche conservatism.

Ecol Evol 2019 Nov 25;9(22):12658-12675. Epub 2019 Oct 25.

Laboratoire d'Ecologie Alpine (LECA) CNRS Université Grenoble Alpes Grenoble France.

Invasive species can encounter environments different from their source populations, which may trigger rapid adaptive changes after introduction (niche shift hypothesis). To test this hypothesis, we investigated whether postintroduction evolution is correlated with contrasting environmental conditions between the European invasive and source ranges in the Asian tiger mosquito . The comparison of environmental niches occupied in European and source population ranges revealed more than 96% overlap between invasive and source niches, supporting niche conservatism. However, we found evidence for postintroduction genetic evolution by reanalyzing a published ddRADseq genomic dataset from 90 European invasive populations using genotype-environment association (GEA) methods and generalized dissimilarity modeling (GDM). Three loci, among which a putative heat-shock protein, exhibited significant allelic turnover along the gradient of winter precipitation that could be associated with ongoing range expansion. Wing morphometric traits weakly correlated with environmental gradients within Europe, but wing size differed between invasive and source populations located in different climatic areas. Niche similarities between source and invasive ranges might have facilitated the establishment of populations. Nonetheless, we found evidence for environmental-induced adaptive changes after introduction. The ability to rapidly evolve observed in invasive populations (genetic shift) together with a large proportion of unfilled potential suitable areas (80%) pave the way to further spread of in Europe.
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http://dx.doi.org/10.1002/ece3.5734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875661PMC
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.
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http://dx.doi.org/10.1371/journal.pntd.0007756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776364PMC
September 2019

Evaluation and Comparison of Spray Equipment for Indoor Residual Spraying.

J Am Mosq Control Assoc 2019 06;35(2):107-112

The World Health Organization (WHO) has recently recommended indoor residual spraying (IRS) as part of a vector control strategy to combat -borne diseases, including dengue, chikungunya, and Zika viruses. Hand compression sprayers have been used in malaria prevention and control programs worldwide since the 1950s and are a standard for IRS application. However, there are technological advances that should be considered to improve IRS application (e.g., flow-control valves, rechargeable-battery equipment, reduced-drift nozzles, etc.), particularly if interventions are performed in urban areas to target . Using WHO guidelines, we contrasted technical characteristics of potential IRS equipment including hand compression sprayers (Hudson X-pert, Goizper IK Vector Control Super), rechargeable-battery sprayers (Solo 416, Birchmeier REC 15ABZ, Hudson NeverPump), and motorized sprayers (Honda WJR 2525, Kawashima AK35GX). Measurements included flow rate, droplet size, battery/fuel life, and technical/physical characteristics. Flow rate, the most important parameter, of the Hudson X-pert was stabilized at 550 ml/min by the use of a control flow valve (CFV). The IK Vector Control Super had integrated CFVs and produced a similar flow as the Hudson X-pert. Rechargeable-battery equipment provided consistent flow as well as negligible noise. Motorized sprayers also produced consistent flow, but their weight, high noise pollution when used indoors, and high engine temperature made them highly unpleasant for technicians. We identify alternatives to the more traditional hand compression Hudson X-pert sprayer with technical and operational considerations for performing IRS.
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http://dx.doi.org/10.2987/18-6810.1DOI Listing
June 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.
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http://dx.doi.org/10.1371/journal.pntd.0007255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542505PMC
May 2019

Entomological Efficacy of Aerial Ultra-Low Volume Insecticide Applications Against Aedes aegypti (Diptera: Culicidae) in Mexico.

J Med Entomol 2019 09;56(5):1331-1337

Collaborative Unit for Entomological Bioassays, Campus de Ciencias Biológicas y Agropecuarias, Universidad Autónoma de Yucatan. Merida, Yucatan, Mexico.

A cluster-randomized controlled trial quantified the entomological efficacy of aerial ultra-low volume (AULV) applications of the insecticide chlorpyrifos against Aedes aegypti in Puerto Vallarta, México, during November-October 2017. The trial involved 16 large (1 × 1 km) clusters distributed between treatment-control arms. Primary endpoint was the abundance of Ae. aegypti indoors (total adults, females, and blood-fed females) collected using Prokopack aspirators. After four consecutive weekly cycles of AULV, all adult Ae. aegypti infestation indices were significantly lower in the treatment arm (OR and IRR ≤ 0.28). Efficacy in reducing indoor Ae. aegypti increased with each weekly application cycle from 30 to 73% (total adults), 33 to 76% (females), and 45.5 to 89% (blood-fed females). Entomological indices remained significantly lower in the treatment arm up to 2 wk after the fourth spraying round. Performing AULV spraying can have significant and lasting entomological impact on Ae. aegypti as long as multiple (ideally four) spray cycles are implemented using an effective insecticide.
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http://dx.doi.org/10.1093/jme/tjz066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736365PMC
September 2019

Feeding Success and Host Selection by Say Mosquitoes in Experimental Trials.

Vector Borne Zoonotic Dis 2019 07 9;19(7):540-548. Epub 2019 Apr 9.

1 Program in Population Biology, Ecology and Evolution, Emory University, Atlanta, Georgia.

Arthropod vector feeding preferences are defined as an overutilization of a particular host species given its abundance in relationship to other species in the community. Numerous methods exist to quantify vector feeding preferences; however, controlled host choice experiments are generally an underutilized approach. In this report, we present results from controlled vector host choice experiments using Say (Diptera: Culicidae) mosquitoes and wild avian hosts identified as important contributors to West Nile virus (WNv) transmission in Atlanta, Georgia, United States. In each experiment, we allowed lab-reared to feed freely overnight on two avian individuals of a different species (, northern cardinals, American robins, blue jays, brown thrashers, and gray catbirds). We then estimated WNv transmission potential using vectorial capacity and . We found that mosquito blood feeding success was extremely variable among experimental replicates and that patterns of host choice only occasionally aggregated to a particular bird species. Vectorial capacity was highest for American robins and blue jays due to these species' higher reservoir competence for WNv and greater probabilities of mosquito selection of these species. Despite species-specific differences in vectorial capacity, total community capacity was similar among species pairs. estimates were qualitatively similar to capacity, and was below and above unity across species pairs. Our results provide empirical evidence that is an opportunistic blood feeder and highlight how variability in vector-host contact rates as well as host community composition can influence the likelihood of WNv transmission in avian communities.
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http://dx.doi.org/10.1089/vbz.2018.2381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625648PMC
July 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.
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http://dx.doi.org/10.1371/journal.pcbi.1006710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443188PMC
March 2019

Efficacy of novel indoor residual spraying methods targeting pyrethroid-resistant Aedes aegypti within experimental houses.

PLoS Negl Trop Dis 2019 02 28;13(2):e0007203. Epub 2019 Feb 28.

Department of Environmental Sciences, Emory University, Atlanta, Georgia, United States of America.

Challenges in maintaining high effectiveness of classic vector control in urban areas has renewed the interest in indoor residual spraying (IRS) as a promising approach for Aedes-borne disease prevention. While IRS has many benefits, application time and intrusive indoor applications make its scalability in urban areas difficult. Modifying IRS to account for Ae. aegypti resting behavior, named targeted IRS (TIRS, spraying walls below 1.5 m and under furniture) can reduce application time; however, an untested assumption is that modifications to IRS will not negatively impact entomological efficacy. We conducted a comparative experimental study evaluating the residual efficacy of classically-applied IRS (as developed for malaria control) compared to two TIRS application methods using a carbamate insecticide against a pyrethroid-resistant, field-derived Ae. aegypti strain. We performed our study within a novel experimental house setting (n = 9 houses) located in Merida (Mexico), with similar layouts and standardized contents. Classic IRS application (insecticide applied to full walls and under furniture) was compared to: a) TIRS: insecticide applied to walls below 1.5 m and under furniture, and b) Resting Site TIRS (RS-TIRS): insecticide applied only under furniture. Mosquito mortality was measured eight times post-application (out to six months post-application) by releasing 100 Ae. aegypti females /house and collecting live and dead individuals after 24 hrs exposure. Compared to Classic IRS, TIRS and RS-TIRS took less time to apply (31% and 82% reduction, respectively) and used less insecticide (38% and 85% reduction, respectively). Mortality of pyrethroid-resistant Ae. aegypti did not significantly differ among the three IRS application methods up to two months post application, and did not significantly differ between Classic IRS and TIRS up to four months post application. These data illustrate that optimizing IRS to more efficiently target Ae. aegypti can both reduce application time and insecticide volume with no apparent reduction in entomological efficacy.
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http://dx.doi.org/10.1371/journal.pntd.0007203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394901PMC
February 2019

Fine-scale spatial and temporal dynamics of kdr haplotypes in Aedes aegypti from Mexico.

Parasit Vectors 2019 Jan 9;12(1):20. Epub 2019 Jan 9.

Department of Environmental Sciences, Emory University, Atlanta, GA, USA.

Background: As resistance to insecticides increases in disease vectors, it has become exceedingly important to monitor populations for susceptibility. Most studies of field populations of Aedes aegypti have largely characterized resistance patterns at the spatial scale of the city or country, which may not be completely informative given that insecticide application occurs at the scale of the house or city block. Phenotypic resistance to pyrethroids dominates in Ae. aegypti, and it has been partially explained by mutations in the voltage-gated sodium channel gene. Here, we assess community-level patterns of four knockdown resistance (kdr) haplotypes (C1534/I1016, F1534/I1016, C1534/V1016 and F1534/V1016) in Ae. aegypti in 24 randomly chosen city blocks from a city in Yucatán State, Mexico, during both the dry and wet season and over two years.

Results: Three of the four haplotypes, C1534/I1016, C1534/V1016 and F1534/V1016 were heterogeneous between city blocks at all four sampling time points, and the double mutant haplotype, C1534/I1016, showed a significant increase following the wet season. The F1534/I1016 haplotype was rarely detected, similar to other studies. However, when haplotype frequencies were aggregated to a coarser spatial scale, the differences in space and time were obscured.

Conclusions: Our results provide empirical evidence that the selection of kdr alleles is occurring at fine spatial scales, indicating that future studies should include this scale to better understand evolutionary processes of resistance in natural populations.
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http://dx.doi.org/10.1186/s13071-018-3275-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327429PMC
January 2019

Community-based surveillance and control of chagas disease vectors in remote rural areas of the Argentine Chaco: A five-year follow-up.

Acta Trop 2019 Mar 26;191:108-115. Epub 2018 Dec 26.

Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Laboratory of Eco-Epidemiology, Ciudad Universitaria, C1428EHA, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas-Universidad de Buenos Aires. Instituto de Ecología, Genética y Evolución de Buenos Aires (IEGEBA), Ciudad Universitaria, C1428EHA, Buenos Aires, Argentina.

Prevention of Chagas disease vector-borne transmission mostly relies on the residual application of pyrethroid insecticide. Persistent or recurrent house infestation after insecticide spraying remains a serious challenge in remote, resource-poor rural areas where public health services face substantial constraints. Here we use generalized estimating equations and multimodel inference to model the fine-scale, time-lagged effects of a community-based vector surveillance-and-response strategy on house infestation and abundance of Triatoma infestans in four rural communities of the Argentine Chaco over a five-year period. Householders and community leaders were trained to detect triatomines and spray with insecticides their premises if infested. House infestation and vector abundance were consistently higher in peridomestic habitats than in human habitations (domiciles). Householders supplemented with sensor boxes detected infested domiciles (67%) more frequently than timed-manual searches (49%). Of all houses ever found to be infested by timed-manual searches, 76% were sprayed within six months upon detection. Domestic triatomine abundance was significantly related to house-level insecticide spraying during the previous year (inversely) and current peridomestic abundance (positively). Peridomestic triatomine abundance significantly increased with current domestic bug abundance and maximum peridomestic abundance during the previous year, and was unaffected by insecticide spraying. Our study provides new empirical evidence of the interconnection and flow between domestic and peridomestic populations of T. infestans under recurrent insecticide treatments, and supports targeting both habitats with appropriate tactics for longer-lasting, improved vector control. Community-directed efforts succeeded in controlling domestic infestations and interrupting domestic transmission, whereas persistent peridomestic infestations demand sustained control efforts to address domestic reinvasions.
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http://dx.doi.org/10.1016/j.actatropica.2018.12.038DOI Listing
March 2019

Dengue seroprevalence in a cohort of schoolchildren and their siblings in Yucatan, Mexico (2015-2016).

PLoS Negl Trop Dis 2018 11 21;12(11):e0006748. Epub 2018 Nov 21.

Center for Health Systems Research, National Institute of Public Health, Mexico City, Mexico.

Background: The implementation of vector control interventions and potential introduction new tools requires baseline data to evaluate their direct and indirect effects. The objective of the study is to present the seroprevalence of dengue infection in a cohort of children 0 to 15 years old followed during 2015 to 2016, the risk factors and the role of enhanced surveillance strategies in three urban sites (Merida, Ticul and Progreso) in Yucatan, Mexico.

Methods: A cohort of school children and their family members was randomly selected in three urban areas with different demographic, social conditions and levels of transmission. We included results from 1,844 children aged 0 to 15 years. Serum samples were tested for IgG, NS1 and IgM. Enhanced surveillance strategies were established in schools (absenteeism) and cohort families (toll-free number).

Results: Seroprevalence in children 0 to 15 years old was 46.8 (CI 95% 44.1-49.6) with no difference by sex except in Ticul. Prevalence increased with age and was significantly lower in 0 to 5 years old (26.9%, 95% CI:18.4-35.4) compared with 6 to 8 years old (43.9%, 95% CI:40.1-47.7) and 9 to 15 years old (61.4%, 95% CI:58.0-64.8). Sharing the domestic space with other families increased the risk 1.7 times over the individual families that own or rented their house, while risk was significantly higher when kitchen and bathroom were outside. Complete protection with screens in doors and windows decreased risk of infection. Seroprevalence was significantly higher in the medium and high risk areas.

Conclusions: The prevalence of antibodies in children 0 to 15 years in three urban settings in the state of Yucatan describe the high exposure and the heterogenous transmission of dengue virus by risk areas and between schools in the study sites. The enhanced surveillance strategy was useful to improve detection of dengue cases with the coincident transmission of chikungunya and Zika viruses.
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http://dx.doi.org/10.1371/journal.pntd.0006748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6248890PMC
November 2018

Epidemiology of dengue and other arboviruses in a cohort of school children and their families in Yucatan, Mexico: Baseline and first year follow-up.

PLoS Negl Trop Dis 2018 11 21;12(11):e0006847. Epub 2018 Nov 21.

Center for Health Systems Research, National Institute of Public Health, Cuernavaca, Morelos, Mexico.

Dengue is the most prevalent mosquito-borne viral disease of humans and is caused by the four serotypes of dengue virus. To estimate the incidence of dengue and other arboviruses, we analyzed the baseline and first year follow-up of a prospective school-based cohort study and their families in three cities in the state of Yucatan, Mexico. Through enhanced surveillance activities, acute febrile illnesses in the participants were detected and yearly blood samples were collected to evaluate dengue infection incidence. A Cox model was fitted to identify hazard ratios of arboviral infections in the first year of follow-up of the cohort. The incidence of dengue symptomatic infections observed during the first year of follow-up (2015-2016) was 3.5 cases per 1,000 person-years (95% CI: 1.9, 5.9). The incidence of dengue infections was 33.9 infections per 1,000 person-years (95% CI: 31.7, 48.0). The majority of dengue infections and seroconversions were observed in the younger age groups (≤ 14 years old). Other arboviruses were circulating in the state of Yucatan during the study period. The incidence of symptomatic chikungunya infections was 8.6 per 1,000 person-years (95% CI: 5.8, 12.3) and the incidence of symptomatic Zika infections was 2.3 per 1,000 person-years (95% CI: 0.9, 4.5). Our model shows that having a dengue infection during the first year of follow-up was significantly associated with being female, living in Ticul or Progreso, and being dengue naïve at baseline. Age was not significantly associated with the outcome, it was confounded by prior immunity to dengue that increases with age. This is the first report of a cohort in Latin America that provides incidence estimates of the three arboviruses co-circulating in all age groups. This study provides important information for understanding the epidemiology of dengue and other arboviruses and better informing public health policies.
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http://dx.doi.org/10.1371/journal.pntd.0006847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6248893PMC
November 2018

Larviciding Culex spp. (Diptera: Culicidae) Populations in Catch Basins and Its Impact on West Nile Virus Transmission in Urban Parks in Atlanta, GA.

J Med Entomol 2019 01;56(1):222-232

Program in Population Biology, Ecology, and Evolution, Emory University, Atlanta, GA.

In urban environments, road-side catch basins are common larval habitats of Culex spp. (Diptera: Culicidae) mosquitoes and important targets of larval control in areas subject to West Nile virus (WNv) transmission. We quantified the impact of larviciding basins on Culex spp. populations and WNv infection prevalence by treating basins in and around urban parks in Atlanta, GA, using Mosquito Dunks and Bits (active ingredient, a.i., Bacillus thuringiensis subsp. isrealensis, Dunks-10.31%, Bits-2.86%) and Altosid 30-Day Briquets (a.i., S-methoprene 8.62%) in two separate seasons. Treatments were coupled with WNv surveillance using gravid traps and aspiration of adults resting in basins. Larviciding led to >90% reductions in Culex spp. larval and pupal collections (Dunks/Bits) and >90% pupal mortality (Briquets) in treated sites during treatment periods; however, we did not observe significant reductions in Culex spp. collections in gravid traps (general linear mixed-effects model [GLMM] result, P > 0.1) or in adults collected resting in basins (GLMM, P > 0.5). In addition, WNv infection prevalence in Culex spp. mosquitoes was similar between treated and untreated sites (GLMM, P > 0.05). Larval control remains important for controlling WNv in Atlanta; however, at the scale and frequency applied in our study, larval control alone may not lead to meaningful reductions in adult populations and WNv infection prevalence. A greater understanding of the annual dynamics of Culex spp. breeding and the importance of basins as Culex spp. larval habitats are needed to meaningfully affect WNv in cities such as Atlanta.
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http://dx.doi.org/10.1093/jme/tjy174DOI Listing
January 2019

Experimental evaluation of the impact of household aerosolized insecticides on pyrethroid resistant Aedes aegypti.

Sci Rep 2018 08 22;8(1):12535. Epub 2018 Aug 22.

Department of Environmental Sciences, Emory University, Atlanta, GA, USA.

The extensive reliance on insecticides to control Aedes aegypti mosquitoes and disrupt transmission of dengue, chikungunya and Zika has fueled the emergence of widespread resistance to insecticides. Mismatch between the frequency of pyrethroid resistance in mosquitoes and the occurrence of pyrethroid-based insecticide applications for vector control is often hypothesized to be due to household use of commercial insecticide products. We experimentally quantified phenotypic and genotypic responses of four Ae. aegypti strains (three field, pyrethroid resistant, and one laboratory, pyrethroid susceptible) after exposure to two commonly used household aerosol insecticide products (a space spray and a residual spray formulation) containing pyrethroid active ingredients. Experiments were performed within homes of Mérida, Mexico. After exposure to the products, all three pyrethroid resistant field Ae. aegypti strains had significantly lower mortality rates (averaging 41% and 50% for the two products, respectively) than the controls (99%). Applying insecticides as surface sprays led to a significant increase in the frequency of I1016 kdr homozygotes in surviving Ae. aegypti, suggesting strong selection pressure for this allele. Given the large-scale use of household aerosol insecticide products in areas that are endemic for Ae. aegypti-transmitted diseases, their role as a pyrethroid resistance selection source, particularly when used as space sprays, should be taken into consideration when designing resistance management plans.
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http://dx.doi.org/10.1038/s41598-018-30968-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105583PMC
August 2018

Forecasting the effectiveness of indoor residual spraying for reducing dengue burden.

PLoS Negl Trop Dis 2018 06 25;12(6):e0006570. Epub 2018 Jun 25.

Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA.

Background: Historically, mosquito control programs successfully helped contain malaria and yellow fever, but recent efforts have been unable to halt the spread of dengue, chikungunya, or Zika, all transmitted by Aedes mosquitoes. Using a dengue transmission model and results from indoor residual spraying (IRS) field experiments, we investigated how IRS-like campaign scenarios could effectively control dengue in an endemic setting.

Methods And Findings: In our model, we found that high levels of household coverage (75% treated once per year), applied proactively before the typical dengue season could reduce symptomatic infections by 89.7% (median of 1000 simulations; interquartile range [IQR]:[83.0%, 94.8%]) in year one and 78.2% (IQR: [71.2%, 88.0%]) cumulatively over the first five years of an annual program. Lower coverage had correspondingly lower effectiveness, as did reactive campaigns. Though less effective than preventative campaigns, reactive and even post-epidemic interventions retain some effectiveness; these campaigns disrupt inter-seasonal transmission, highlighting an off-season control opportunity. Regardless, none of the campaign scenarios maintain their initial effectiveness beyond two seasons, instead stabilizing at much lower levels of benefit: in year 20, median effectiveness was only 27.3% (IQR: [-21.3%, 56.6%]). Furthermore, simply ceasing an initially successful program exposes a population with lowered herd immunity to the same historical threat, and we observed outbreaks more than four-fold larger than pre-intervention outbreaks. These results do not take into account evolving insecticide resistance, thus long-term effectiveness may be lower if new, efficacious insecticides are not developed.

Conclusions: Using a detailed agent-based dengue transmission model for Yucatán State, Mexico, we predict that high coverage indoor residual spraying (IRS) interventions can largely eliminate transmission for a few years, when applied a few months before the typical seasonal epidemic peak. However, vector control succeeds by preventing infections, which precludes natural immunization. Thus, as a population benefits from mosquito control, it gradually loses naturally acquired herd immunity, and the control effectiveness declines; this occurs across all of our modeled scenarios, and is consistent with other empirical work. Long term control that maintains early effectiveness would require some combination of increasing investment, complementary interventions such as vaccination, and control programs across a broad region to diminish risk of importation.
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http://dx.doi.org/10.1371/journal.pntd.0006570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042783PMC
June 2018

Restoration of pyrethroid susceptibility in a highly resistant population.

Biol Lett 2018 06;14(6)

Emory University, Atlanta, GA, USA.

Insecticide resistance has evolved in disease vectors worldwide, creating the urgent need to either develop new control methods or restore insecticide susceptibility to regain use of existing tools. Here we show that phenotypic susceptibility can be restored in a highly resistant field-derived strain of in only 10 generations through rearing them in the absence of insecticide.
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http://dx.doi.org/10.1098/rsbl.2018.0022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030600PMC
June 2018
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