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BACKGROUND: Aedes aegypti is the primary mosquito vector for several arboviruses, such as dengue, chikungunya and Zika viruses, which cause frequent outbreaks of human disease in tropical and subtropical regions. Control of these outbreaks relies on vector control, commonly in the form of insecticide sprays that target adult female mosquitoes. However, the spatial coverage and frequency of sprays needed to optimize effectiveness are unclear. In this study, we characterize the effect of ultra-low-volume (ULV) indoor spraying of pyrethroid insecticides on Ae. aegypti abundance within households. We also evaluate the effects of spray events during recent time periods or in neighboring households. Improved understanding of the duration and distance of the impact of a spray intervention on Ae. aegypti populations can inform vector control interventions, in addition to modeling efforts that contrast vector control strategies. METHODS: This project analyzes data from two large-scale experiments that involved six cycles of indoor pyrethroid spray applications in 2 years in the Amazonian city of Iquitos, Peru. We developed spatial multi-level models to disentangle the reduction in Ae. aegypti abundance that resulted from (i) recent ULV treatment within households and (ii) ULV treatment of adjacent or nearby households. We compared fits of models across a range of candidate weighting schemes for the spray effect, based on different temporal and spatial decay functions to understand lagged ULV effects. RESULTS: Our results suggested that the reduction of Ae. aegypti in a household was mainly due to spray events occurring within the same household, with no additional effect of sprays that occurred in neighboring households. Effectiveness of a spray intervention should be measured based on time since the most recent spray event, as we found no cumulative effect of sequential sprays. Based on our model, we estimated the spray effect is reduced by 50% approximately 28 days after the spray event. CONCLUSIONS: The reduction of Ae. aegypti in a household was mainly determined by the number of days since the last spray intervention in that same household, highlighting the importance of spray coverage in high-risk areas with a spray frequency determined by local viral transmission dynamics.
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Aedes , Composición Familiar , Insecticidas , Control de Mosquitos , Mosquitos Vectores , Piretrinas , Análisis Espacio-Temporal , Animales , Aedes/efectos de los fármacos , Insecticidas/farmacología , Insecticidas/administración & dosificación , Control de Mosquitos/métodos , Mosquitos Vectores/efectos de los fármacos , Piretrinas/farmacología , Femenino , Perú , Humanos , Densidad de Población , Dengue/prevención & control , Dengue/transmisiónRESUMEN
Background: Dengue poses a significant public health challenge in Peru and other endemic countries worldwide. While severe dengue is known to be associated with secondary infection at the individual level, the factors that elevate the risk of severe dengue at the population level remain poorly understood. This study leverages over 16 years of secondary data from a Peruvian dengue surveillance system to assess which type of serotype-specific circulation is associated with an increased risk of cumulative incidence of severe dengue or dengue with warning signs (SD-DWS). Methodology: This is a retrospective analysis of secondary data using the Peruvian Ministry of Health databases of dengue cases and serotyping. A mixed negative binomial regression model for repeated measures over time was employed to estimate the association between the cumulative incidence of reported SD-DWS cases per 100,000 inhabitants and serotype-specific circulation. Crude and adjusted incidence ratios (IRR) were estimated. Principal findings: The study analyzed data from 2007 to 2022 across 19 regions of Peru, totaling 304 region-years. Data from nearly 58,000 serotype identification reports and 57,966 cases of SD-DWS were analyzed. The regions with most cumulative incidence of SD-DWS per 100,000 inhabitants during 2007 to 2022 were Madre de Dios (3859), Loreto (1518), Ucayali (1492), Tumbes (1335), and Piura (722). The adjusted model revealed a higher risk of cumulative incidence of SD-DWS when there was specific circulation of DENV-123 (aIRR 7.57 CI 4.00 - 14.31), DENV-12 (aIRR 4.66 CI 2.57 - 8.44), DENV-23 (aIRR 3.55 CI 1.75 - 7.21), or when there was circulation of DENV-2 alone or co-circulating with other serotypes (aIRR 27.7 CI 15.46 -49.63). Conclusions: Circulation of DENV-2 was associated with higher average incidence rate ratios of SD-DWS. Author summary: We investigated how the circulation of different dengue virus (DENV) serotypes are associated with the incidence of severe dengue and dengue with warning signs in Peru, a country where dengue is endemic. We analyzed 16 years of data from the dengue surveillance system, including nearly 58,000 serotype identification reports and 57,966 cases of severe dengue and dengue with warning signs. We found that regions with specific circulation of DENV-2, either alone or in combination with other serotypes, had higher incidence rates of severe dengue and dengue with warning signs. Our findings highlight the importance of monitoring DENV serotype circulation to manage and prevent severe dengue, especially in regions where DENV-2 is prevalent.
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Dengue virus (DENV) transmission from humans to mosquitoes is a poorly documented, but critical component of DENV epidemiology. Magnitude of viremia is the primary determinant of successful human-to-mosquito DENV transmission. People with the same level of viremia, however, can vary in their infectiousness to mosquitoes as a function of other factors that remain to be elucidated. Here, we report on a field-based study in the city of Iquitos, Peru, where we conducted direct mosquito feedings on people naturally infected with DENV and that experienced mild illness. We also enrolled people naturally infected with Zika virus (ZIKV) after the introduction of ZIKV in Iquitos during the study period. Of the 54 study participants involved in direct mosquito feedings, 43 were infected with DENV-2, two with DENV-3, and nine with ZIKV. Our analysis excluded participants whose viremia was detectable at enrollment but undetectable at the time of mosquito feeding, which was the case for all participants with DENV-3 and ZIKV infections. We analyzed the probability of onward transmission during 50 feeding events involving 27 participants infected with DENV-2 based on the presence of infectious virus in mosquito saliva 7-16 days post blood meal. Transmission probability was positively associated with the level of viremia and duration of extrinsic incubation in the mosquito. In addition, transmission probability was influenced by the day of illness in a non-monotonic fashion; i.e., transmission probability increased until 2 days after symptom onset and decreased thereafter. We conclude that mildly ill DENV-infected humans with similar levels of viremia during the first two days after symptom onset will be most infectious to mosquitoes on the second day of their illness. Quantifying variation within and between people in their contribution to DENV transmission is essential to better understand the biological determinants of human infectiousness, parametrize epidemiological models, and improve disease surveillance and prevention strategies.
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Culicidae , Dengue , Infección por el Virus Zika , Virus Zika , Animales , Humanos , Viremia , Infección por el Virus Zika/epidemiología , Dengue/epidemiologíaRESUMEN
BACKGROUND: Dengue is the most prevalent arboviral infection causing an estimated 50-60 million cases of febrile illness globally per year, exacting considerable disease burden. Few instruments exist to assess the patient illness experience, with most based on healthcare provider assessment, lacking standardization in timepoints and symptom assessment. This study aimed to evaluate the content validity of the novel 'Dengue Virus Daily Diary (DENV-DD)', designed to measure symptom intensity and disease burden within outpatient infant to adult populations. METHODS: The Dengue Illness Index Report Card was used as a foundation to create the DENV-DD, consisting of patient- and observer-reported outcome (PRO/ObsRO) instruments. In two South American dengue-endemic communities, qualitative combined concept elicitation and cognitive debriefing interviews were conducted among individuals and caregivers of children with symptomatic laboratory-confirmed dengue. Interviews were conducted across two rounds allowing DENV-DD modifications. A small-scale quantitative assessment of the DENV-DD was also conducted with data from an independent Dengue Human Infection Model (DHIM) to generate early evidence of feasibility of DENV-DD completion, instrument performance and insight into the sign/symptom trajectory over the course of illness. RESULTS: Forty-eight participants were interviewed (20 adults, 20 older children/adolescents with their caregivers, 8 caregivers of younger children). A wide spectrum of signs/symptoms lasting 3-15 days were reported with fever, headache, body ache/pain, loss of appetite, and body weakness each reported by > 70% participants. DENV-DD instructions, items and response scales were understood, and items were considered relevant across ages. DHIM data supported feasibility of DENV-DD completion. CONCLUSIONS: Findings demonstrate content validity of the DENV-DD (PRO/ObsRO instruments) in dengue-endemic populations. Psychometric and cultural validity studies are ongoing to support use of the DENV-DD in clinical studies.
Dengue is the most common viral infection transmitted to humans by mosquitos, and affects an estimated 5060 million individuals globally per year. However, there are few resources for understanding and capturing the patient experience of dengue throughout illness. Most research studies are based on healthcare provider assessment, which lack consistency in terms of assessment time points and the signs/symptoms assessed. The 'Dengue Illness Index Report Card (DII-RC)' was used as a foundation to create the new 'Dengue Virus Daily Diary (DENV-DD)' to better capture the patient experience of symptom intensity and dengue disease burden for the duration of illness. Forty-eight individuals and caregivers of younger children from Peru and Ecuador who recently had symptomatic dengue were interviewed to understand the patient experience over the time of illness and to test whether the DENV-DD is understood by patients and caregivers and includes all relevant and important signs/symptoms and health-related quality of life impacts. Nine individuals with active dengue infection also completed the DENV-DD daily for 28-days as part of a clinical study. We found that > 70% of patients experienced fever, headache, body ache/pain, loss of appetite and body weakness. The DENV-DD instructions, questions and response option(s) were well understood, feasible to complete and the concepts assessed by the DENV-DD were relevant to the dengue experience. Our study adds to the understanding of the dengue illness experience and supports the DENV-DD for use in future dengue studies as an assessment of signs/symptoms throughout the duration of illness.
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Cardiología , Virus del Dengue , Dengue , Adolescente , Adulto , Niño , Lactante , Humanos , Apetito , Costo de Enfermedad , Dolor , Dengue/diagnósticoRESUMEN
Entomological research studies on mosquito vector biology, vector competence, insecticide resistance, dispersal, and survival (using mark-release-recapture techniques) often rely on laboratory-reared mosquito colonies to produce large numbers of consistently reared, aged, and sized mosquitoes. We developed a low-cost blood feeding apparatus that supports temperatures consistent with warm blooded animals, using commonly available materials found in low resource environments. We compare our system ("Caserotek") to Hemotek and glass/membrane feeding methods. Two experiments were conducted with Aedes aegypti (Linnaeus 1762) and one with Anopheles darlingi (Root 1926) (Diptera: Culicidae); 3 replicates were conducted for each experiment. Aedes aegypti female mosquitoes were provided chicken blood once per week for 30 min (Experiment #1) for 14 days or 1 hour (Experiment #2) for 21 days. Anopheles darlingi were fed once for 1 hour (Experiment #3). Blood-feeding rates, survival rates, and egg production were calculated across replicates. Caserotek had a significantly higher 30-min engorgement rate (91.1%) than Hemotek (47.7%), and the glass feeder (29.3%) whereas for 1-hour feeding, Hemotek had a significantly lower engorgement rate than either of the other two devices (78% versus 91%). Thirty-day survival was similar among the feeding devices, ranging from 86% to 99%. Mean egg production was highest for the Caserotek feeder (32 eggs per female) compared to the glass feeder and Hemotek device (21-22 eggs per female). Our new artificial feeding system had significantly higher blood feeding rates than for more expensive artificial systems and was equivalent to other fitness parameters. Caserotek only requires the ability to boil water to maintain blood temperatures using a Styrofoam liner. It can be easily scaled up to large production facilities and used under austere conditions.
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Aedes , Anopheles , Sustitutos Sanguíneos , Femenino , Animales , Temperatura Corporal , PollosRESUMEN
BACKGROUND: Transmission models have a long history in the study of mosquito-borne disease dynamics. The mosquito biting rate (MBR) is an important parameter in these models, however, estimating its value empirically is complex. Modeling studies obtain biting rate values from various types of studies, each of them having its strengths and limitations. Thus, understanding these study designs and the factors that contribute to MBR estimates and their variability is an important step towards standardizing these estimates. We do this for an important arbovirus vector Aedes aegypti. METHODOLOGY/PRINCIPAL FINDINGS: We perform a systematic review using search terms such as 'biting rate' and 'biting frequency' combined with 'Aedes aegypti' ('Ae. aegypti' or 'A. aegypti'). We screened 3,201 articles from PubMed and ProQuest databases, of which 21 met our inclusion criteria. Two broader types of studies are identified: human landing catch (HLC) studies and multiple feeding studies. We analyze the biting rate data provided as well as the methodologies used in these studies to characterize the variability of these estimates across temporal, spatial, and environmental factors and to identify the strengths and limitations of existing methodologies. Based on these analyses, we present two approaches to estimate population mean per mosquito biting rate: one that combines studies estimating the number of bites taken per gonotrophic cycle and the gonotrophic cycle duration, and a second that uses data from histological studies. Based on one histological study dataset, we estimate biting rates of Ae. aegypti (0.41 and 0.35 bite/mosquito-day in Thailand and Puerto Rico, respectively). CONCLUSIONS/SIGNIFICANCE: Our review reinforces the importance of engaging with vector biology when using mosquito biting rate data in transmission modeling studies. For Ae. aegypti, this includes understanding the variation of the gonotrophic cycle duration and the number of bites per gonotrophic cycle, as well as recognizing the potential for spatial and temporal variability. To address these variabilities, we advocate for site-specific data and the development of a standardized approach to estimate the biting rate.
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Aedes , Mordeduras y Picaduras de Insectos , Animales , Humanos , Mosquitos Vectores , Mordeduras y Picaduras de Insectos/epidemiología , Tailandia/epidemiología , Conducta AlimentariaRESUMEN
BACKGROUND: After the unprecedented Zika virus (ZIKV) outbreak in the western hemisphere from 2015-2018, Aedes aegypti and Ae. albopictus are now well established primary and secondary ZIKV vectors, respectively. Consensus about identification and importance of other secondary ZIKV vectors remain. This systematic review aims to provide a list of vector species capable of transmitting ZIKV by reviewing evidence from laboratory vector competence (VC) studies and to identify key knowledge gaps and issues within the ZIKV VC literature. METHODS: A search was performed until 15th March 2022 on the Cochrane Library, Lilacs, PubMed, Web of Science, WHOLIS and Google Scholar. The search strings included three general categories: 1) "ZIKA"; 2) "vector"; 3) "competence", "transmission", "isolation", or "feeding behavior" and their combinations. Inclusion and exclusion criteria has been predefined and quality of included articles was assessed by STROBE and STROME-ID criteria. FINDINGS: From 8,986 articles retrieved, 2,349 non-duplicates were screened by title and abstracts,103 evaluated using the full text, and 45 included in this analysis. Main findings are 1) secondary vectors of interest include Ae. japonicus, Ae. detritus, and Ae. vexans at higher temperature 2) Culex quinquefasciatus was not found to be a competent vector of ZIKV, 3) considerable heterogeneity in VC, depending on the local mosquito strain and virus used in testing was observed. Critical issues or gaps identified included 1) inconsistent definitions of VC parameters across the literature; 2) equivalency of using different mosquito body parts to evaluate VC parameters for infection (mosquito bodies versus midguts), dissemination (heads, legs or wings versus salivary glands), and transmission (detection or virus amplification in saliva, FTA cards, transmission to neonatal mice); 3) articles that fail to use infectious virus assays to confirm the presence of live virus; 4) need for more studies using murine models with immunocompromised mice to infect mosquitoes. CONCLUSION: Recent, large collaborative multi-country projects to conduct large scale evaluations of specific mosquito species represent the most appropriate approach to establish VC of mosquito species.
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Aedes , Infección por el Virus Zika , Virus Zika , Animales , Ratones , Mosquitos Vectores , BioensayoRESUMEN
Dengue has historically been considered an urban disease associated with dense human populations and the built environment. Recently, studies suggest increasing dengue virus (DENV) transmission in rural populations. It is unclear whether these reports reflect recent spread into rural areas or ongoing transmission that was previously unnoticed, and what mechanisms are driving this rural transmission. We conducted a systematic review to synthesize research on dengue in rural areas and apply this knowledge to summarize aspects of rurality used in current epidemiological studies of DENV transmission given changing and mixed environments. We described how authors defined rurality and how they defined mechanisms for rural dengue transmission. We systematically searched PubMed, Web of Science, and Embase for articles evaluating dengue prevalence or cumulative incidence in rural areas. A total of 106 articles published between 1958 and 2021 met our inclusion criteria. Overall, 56% (n = 22) of the 48 estimates that compared urban and rural settings reported rural dengue incidence as being as high or higher than in urban locations. In some rural areas, the force of infection appears to be increasing over time, as measured by increasing seroprevalence in children and thus likely decreasing age of first infection, suggesting that rural dengue transmission may be a relatively recent phenomenon. Authors characterized rural locations by many different factors, including population density and size, environmental and land use characteristics, and by comparing their context to urban areas. Hypothesized mechanisms for rural dengue transmission included travel, population size, urban infrastructure, vector and environmental factors, among other mechanisms. Strengthening our understanding of the relationship between rurality and dengue will require a more nuanced definition of rurality from the perspective of DENV transmission. Future studies should focus on characterizing details of study locations based on their environmental features, exposure histories, and movement dynamics to identify characteristics that may influence dengue transmission.
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Virus del Dengue , Dengue , Niño , Humanos , Estudios Seroepidemiológicos , Estudios Longitudinales , Población RuralRESUMEN
Mosquito-borne diseases are a global burden; however, current methods of evaluating human-mosquito contact rates are expensive and time consuming. Validated surveys of self-reported mosquito bites may be an inexpensive way to determine mosquito presence and bite exposure level in an area, but this remains untested. In this study, a survey of self-reported mosquito bites was validated against household mosquito abundance from six communities in Esmeraldas, Ecuador. From February 2021 to July 2022, households were interviewed monthly, and five questions were used to ask participants how often they were bitten by mosquitoes at different times during the day. At the same time, adult mosquitoes were collected using a Prokopack aspirator. Species were identified and counted. Survey responses were compared with the total number of mosquitoes found in the home using negative binomial regression. More frequent self-reported mosquito bites were significantly associated with higher numbers of collected adult mosquitoes. These associations were driven by the prevalence of the dominant genera, Culex. These results suggest that surveys of perceived mosquito bites relate to actual mosquito presence, making them a potentially useful tool for determining the impact of vector-control interventions on community perceptions of risk but less useful for assessing the risk of nondominant species such as Aedes aegypti. Further work is needed to examine the robustness of these results in other contexts.
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Aedes , Mordeduras y Picaduras de Insectos , Adulto , Animales , Humanos , Autoinforme , Mosquitos Vectores/fisiología , Mordeduras y Picaduras de Insectos/epidemiología , Ecuador/epidemiología , Composición Familiar , Aedes/fisiologíaRESUMEN
The COVID-19 pandemic affected the main Amazon cities dramatically, with Iquitos City reporting the highest seroprevalence of anti-SARS-CoV-2 antibodies during the first COVID-19 wave worldwide. This phenomenon raised many questions about the possibility of a co-circulation of dengue and COVID-19 and its consequences. We carried out a population-based cohort study in Iquitos, Peru. We obtained a venous blood sample from a subset of 326 adults from the Iquitos COVID-19 cohort (August 13-18, 2020) to estimate the seroprevalence of anti-dengue virus (DENV) and anti-SARS-CoV-2 antibodies. We tested each serum sample for anti-DENV IgG (serotypes 1, 2, 3, and 4) and SARS-CoV-2 antibodies anti-spike IgG and IgM by ELISA. We estimated an anti-SARS-CoV-2 seroprevalence of 78.0% (95% CI, 73.0-82.0) and an anti-DENV seroprevalence of 88.0% (95% CI, 84.0-91.6), signifying a high seroprevalence of both diseases during the first wave of COVID-19 transmission in the city. The San Juan District had a lower anti-DENV antibody seroprevalence than the Belen District (prevalence ratio, 0.90; 95% CI, 0.82-0.98). However, we did not observe these differences in anti-SARS-CoV-2 antibody seroprevalence. Iquitos City presented one of the highest seroprevalence rates of anti-DENV and anti-SARS-CoV-2 antibodies worldwide, but with no correlation between their antibody levels.
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COVID-19 , Adulto , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Perú/epidemiología , Estudios de Cohortes , Estudios Seroepidemiológicos , Pandemias , Anticuerpos Antivirales , Inmunoglobulina GRESUMEN
The mosquito Aedes aegypti is the vector of a number of medically-important viruses, including dengue virus, yellow fever virus, chikungunya virus, and Zika virus, and as such vector control is a key approach to managing the diseases they cause. Understanding the impact of vector control on these diseases is aided by first understanding its impact on Ae. aegypti population dynamics. A number of detail-rich models have been developed to couple the dynamics of the immature and adult stages of Ae. aegypti. The numerous assumptions of these models enable them to realistically characterize impacts of mosquito control, but they also constrain the ability of such models to reproduce empirical patterns that do not conform to the models' behavior. In contrast, statistical models afford sufficient flexibility to extract nuanced signals from noisy data, yet they have limited ability to make predictions about impacts of mosquito control on disease caused by pathogens that the mosquitoes transmit without extensive data on mosquitoes and disease. Here, we demonstrate how the differing strengths of mechanistic realism and statistical flexibility can be fused into a single model. Our analysis utilizes data from 176,352 household-level Ae. aegypti aspirator collections conducted during 1999-2011 in Iquitos, Peru. The key step in our approach is to calibrate a single parameter of the model to spatio-temporal abundance patterns predicted by a generalized additive model (GAM). In effect, this calibrated parameter absorbs residual variation in the abundance time-series not captured by other features of the mechanistic model. We then used this calibrated parameter and the literature-derived parameters in the agent-based model to explore Ae. aegypti population dynamics and the impact of insecticide spraying to kill adult mosquitoes. The baseline abundance predicted by the agent-based model closely matched that predicted by the GAM. Following spraying, the agent-based model predicted that mosquito abundance rebounds within about two months, commensurate with recent experimental data from Iquitos. Our approach was able to accurately reproduce abundance patterns in Iquitos and produce a realistic response to adulticide spraying, while retaining sufficient flexibility to be applied across a range of settings.
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Aedes , Virus Chikungunya , Dengue , Infección por el Virus Zika , Virus Zika , Animales , Mosquitos Vectores/fisiología , Dinámica Poblacional , Virus de la Fiebre Amarilla , Dengue/epidemiologíaRESUMEN
Transmission heterogeneity, whereby a disproportionate fraction of pathogen transmission events result from a small number of individuals or geographic locations, is an inherent property of many, if not most, infectious disease systems. For vector-borne diseases, transmission heterogeneity is inferred from the distribution of the number of vectors per host, which could lead to significant bias in situations where vector abundance and transmission risk at the household do not correlate, as is the case with dengue virus (DENV). We used data from a contact tracing study to quantify the distribution of DENV acute infections within human activity spaces (AS), the collection of residential locations an individual routinely visits, and quantified measures of virus transmission heterogeneity from two consecutive dengue outbreaks (DENV-4 and DENV-2) that occurred in the city of Iquitos, Peru. Negative-binomial distributions and Pareto fractions showed evidence of strong overdispersion in the number of DENV infections by AS and identified super-spreading units (SSUs): i.e. AS where most infections occurred. Approximately 8% of AS were identified as SSUs, contributing to more than 50% of DENV infections. SSU occurrence was associated more with DENV-2 infection than with DENV-4, a predominance of inapparent infections (74% of all infections), households with high Aedes aegypti mosquito abundance, and high host susceptibility to the circulating DENV serotype. Marked heterogeneity in dengue case distribution, and the role of inapparent infections in defining it, highlight major challenges faced by reactive interventions if those transmission units contributing the most to transmission are not identified, prioritized, and effectively treated.
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Current knowledge of dengue virus (DENV) transmission provides only a partial understanding of a complex and dynamic system yielding a public health track record that has more failures than successes. An important part of the problem is that the foundation for contemporary interventions includes a series of longstanding, but untested, assumptions based on a relatively small portion of the human population; i.e., people who are convenient to study because they manifest clinically apparent disease. Approaching dengue from the perspective of people with overt illness has produced an extensive body of useful literature. It has not, however, fully embraced heterogeneities in virus transmission dynamics that are increasingly recognized as key information still missing in the struggle to control the most important insect-transmitted viral infection of humans. Only in the last 20 years have there been significant efforts to carry out comprehensive longitudinal dengue studies. This manuscript provides the rationale and comprehensive, integrated description of the methodology for a five-year longitudinal cohort study based in the tropical city of Iquitos, in the heart of the Peruvian Amazon. Primary data collection for this study was completed in 2019. Although some manuscripts have been published to date, our principal objective here is to support subsequent publications by describing in detail the structure, methodology, and significance of a specific research program. Our project was designed to study people across the entire continuum of disease, with the ultimate goal of quantifying heterogeneities in human variables that affect DENV transmission dynamics and prevention. Because our study design is applicable to other Aedes transmitted viruses, we used it to gain insights into Zika virus (ZIKV) transmission when during the project period ZIKV was introduced and circulated in Iquitos. Our prospective contact cluster investigation design was initiated by detecttion of a person with a symptomatic DENV infection and then followed that person's immediate contacts. This allowed us to monitor individuals at high risk of DENV infection, including people with clinically inapparent and mild infections that are otherwise difficult to detect. We aimed to fill knowledge gaps by defining the contribution to DENV transmission dynamics of (1) the understudied majority of DENV-infected people with inapparent and mild infections and (2) epidemiological, entomological, and socio-behavioral sources of heterogeneity. By accounting for factors underlying variation in each person's contribution to transmission we sought to better determine the type and extent of effort needed to better prevent virus transmission and disease.
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Arbovirus , Virus del Dengue , Dengue , Infección por el Virus Zika , Virus Zika , Humanos , Estudios Longitudinales , Estudios Prospectivos , Perú/epidemiología , Infección por el Virus Zika/epidemiologíaRESUMEN
BACKGROUND: Spatial repellents (SRs) have been widely used for prevention of mosquito bites, but their efficacy in reducing Aedes-borne viruses (ABV) has not been tested rigorously at large scale in Asia. To address this knowledge gap, a trial to evaluate the efficacy of Mosquito Shield™, a transfluthrin SR, was developed in Gampaha District of Sri Lanka across three Medical Officer of Health areas; i.e., Negombo, Wattala, and Kelaniya. METHODS: This trial is a cluster-randomized, placebo-controlled, double-blinded clinical trial. A total of ~14,430 subjects aged ≥ 6 months in 30 clusters (15 intervention, 15 placebo) from ~3900 households (HH) will be randomly selected for enrolment into a "febrile surveillance cohort." A subset of the surveillance cohort, ~3570 subjects aged ≥4-16 years that test seronegative (naïve) or are serologically positive for a previous single dengue virus (DENV) infection (monotypic) at baseline sampling, will be enrolled into a "longitudinal cohort" for measuring DENV infection based on laboratory-confirmed seroconversion during the trial. Persons identified positive for antibodies against multiple DENV serotypes (multitypic) at baseline will be monitored for secondary analyses. Active ABV disease will be assessed using an enhanced passive surveillance system with case ascertainment performed in designated healthcare facilities. Serum samples will be taken from longitudinal cohort subjects within 1-2 weeks of when intervention is first deployed (T0) with additional samples taken ~12 (T1) and ~24 months (T2) from baseline sampling. DENV seroconversion and ABV active disease rates from baseline (pre-intervention) and follow-up (post-intervention) samples will be compared between intervention and placebo clusters. Participating houses will be monitored entomologically (indoor adult Aedes aegypti population densities and adult female blood fed status) within 3 months before intervention deployment and monthly during the intervention phase. Entomological surveys will monitor indoor adult Ae. aegypti population densities and blood fed status. Dengue incidence in each cohort will be estimated and compared to determine the public health benefit of using an SR. Entomological parameters will be measured to determine if there are entomological correlates of SR efficacy that may be useful for the evaluation of new SR products. DISCUSSION: The trial will serve as an efficacy assessment of SR products in South Asia. Results will be submitted to the World Health Organization Vector Control Advisory Group for assessment of public health value towards an endorsement to recommend inclusion of SRs in ABV control programs. TRIAL REGISTRATION: Sri Lanka Clinical Trial Registry SLCTR /2022/018. Registered on July 1, 2022. CLINICALTRIALS: gov NCT05452447 . Registered on July 11, 2022. The Universal Trial Number is U1111-1275-3055.
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Aedes , Dengue , Virosis , Adulto , Animales , Niño , Humanos , Femenino , Preescolar , Adolescente , Dengue/diagnóstico , Dengue/epidemiología , Dengue/prevención & control , Sri Lanka/epidemiología , Mosquitos Vectores , Control de Mosquitos/métodos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Spatial repellent (SR) products are envisioned to complement existing vector control methods through the continual release of volatile active ingredients (AI) providing: (i) protection against day-time and early-evening biting; (ii) protection in enclosed/semi-enclosed and peri-domestic spaces; (iii) various formulations to fit context-specific applications; and (iv) increased coverage over traditional control methods. SR product AIs also have demonstrated effect against insecticide-resistant vectors linked to malaria and Aedes-borne virus (ABV) transmission. Over the past two decades, key stakeholders, including World Health Organization (WHO) representatives, have met to discuss the role of SRs in reducing arthropod-borne diseases based on existing evidence. A key focus has been to establish a critical development path for SRs, including scientific, regulatory and social parameters that would constitute an outline for a SR target product profile, i.e. optimum product characteristics. The principal gap is the lack of epidemiological data demonstrating SR public health impact across a range of different ecological and epidemiological settings, to inform a WHO policy recommendation. Here we describe in brief trials that are designed to fulfill evidence needs for WHO assessment and initial projections of SR cost-effectiveness against malaria and dengue.
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The importance of mosquitoes in human pathogen transmission has motivated major research efforts into mosquito biology in pursuit of more effective vector control measures. Aedes aegypti is a particular concern in tropical urban areas, where it is the primary vector of numerous flaviviruses, including the yellow fever, Zika, and dengue viruses. With an anthropophilic habit, Ae. aegypti prefers houses, human blood meals, and ovipositioning in water-filled containers. We hypothesized that this relatively simple ecological niche should allow us to predict the impacts of insecticidal control measures on mosquito populations. To do this, we use Skeeter Buster 2 (SB2), a stochastic, spatially explicit, mechanistic model of Ae. aegypti population biology. SB2 builds on Skeeter Buster, which reproduced equilibrium dynamics of Ae. aegypti in Iquitos, Peru. Our goal was to validate SB2 by predicting the response of mosquito populations to perturbations by indoor insecticidal spraying and widespread destructive insect surveys. To evaluate SB2, we conducted two field experiments in Iquitos, Peru: a smaller pilot study in 2013 (S-2013) followed by a larger experiment in 2014 (L-2014). Here, we compare model predictions with (previously reported) empirical results from these experiments. In both simulated and empirical populations, repeated spraying yielded substantial yet temporary reductions in adult densities. The proportional effects of spraying were broadly comparable between simulated and empirical results, but we found noteworthy differences. In particular, SB2 consistently over-estimated the proportion of nulliparous females and the proportion of containers holding immature mosquitoes. We also observed less temporal variation in simulated surveys of adult abundance relative to corresponding empirical observations. Our results indicate the presence of ecological heterogeneities or sampling processes not effectively represented by SB2. Although additional empirical research could further improve the accuracy and precision of SB2, our results underscore the importance of non-linear dynamics in the response of Ae. aegypti populations to perturbations, and suggest general limits to the fine-grained predictability of its population dynamics over space and time.
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Aedes , Dengue , Insecticidas , Infección por el Virus Zika , Virus Zika , Animales , Femenino , Humanos , Insecticidas/farmacología , Mosquitos Vectores , Perú , Proyectos PilotoAsunto(s)
Aedes , Virosis , Animales , Vectores de Enfermedades , Entomología , Mosquitos Vectores , Literatura de Revisión como AsuntoRESUMEN
Vector-borne diseases are among the most burdensome infectious diseases worldwide with high burden to health systems in developing regions in the tropics. For many of these diseases, vector control to reduce human biting rates or arthropod populations remains the primary strategy for prevention. New vector control interventions intended to be marketed through public health channels must be assessed by the World Health Organization for public health value using data generated from large-scale trials integrating epidemiological endpoints of human health impact. Such phase III trials typically follow large numbers of study subjects to meet necessary power requirements for detecting significant differences between treatment arms, thereby generating substantive and complex datasets. Data is often gathered directly in the field, in resource-poor settings, leading to challenges in efficient data reporting and/or quality assurance. With advancing technology, mobile data collection (MDC) systems have been implemented in many studies to overcome these challenges. Here we describe the development and implementation of a MDC system during a randomized-cluster, placebo-controlled clinical trial evaluating the protective efficacy of a spatial repellent intervention in reducing human infection with Aedes-borne viruses (ABV) in the urban setting of Iquitos, Peru, as well as the data management system that supported it. We discuss the benefits, remaining capacity gaps and the key lessons learned from using a MDC system in this context in detail.
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Aedes , Dengue , Animales , Recolección de Datos , Dengue/epidemiología , Dengue/prevención & control , Humanos , Control de Mosquitos , Mosquitos Vectores , Perú/epidemiología , Proyectos de InvestigaciónRESUMEN
The objective of this study was to determine the etiology of febrile illnesses among patients from October 1, 1993 through September 30, 1999, in the urban community of Iquitos in the Amazon River Basin of Peru. Epidemiological and clinical data as well as blood samples were obtained from consenting patients at hospitals, health clinics and private residences. Samples were tested for arboviruses in cell cultures and for IgM and IgG antibodies by ELISA. Blood smears were examined for malaria, and sera were tested for antibodies to Leptospira spp. by ELISA and microscopic agglutination. Among 6,607 febrile patients studied, dengue viruses caused 14.6% of the cases, and Venezuelan equine encephalitis virus caused 2.5%, Oropouche virus 1.0%, Mayaro virus 0.4%, and other arboviruses caused 0.2% of the cases. Also, 22.9% of 4,844 patients tested were positive for malaria, and of 400 samples tested, 9% had evidence of acute leptospirosis. Although the study was not designed to assess the importance of these pathogens as a cause of human morbidity in the total population, these results indicate that arboviruses, leptospirosis, and malaria were the cause of approximately 50% of the febrile cases. Although the arboviruses that were diagnosed can produce asymptomatic infections, our findings increased the overall understanding of the relative health burden of these infections, as well as baseline knowledge needed for designing and implementing further studies to better assess the health impact and threat of these pathogens in the Amazon Basin of Peru.