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1.
Emerg Infect Dis ; 26(9): 2077-2086, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32818402

RESUMO

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.

2.
PLoS Negl Trop Dis ; 14(7): e0008477, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32722709

RESUMO

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.


Assuntos
Dengue/patologia , Qualidade de Vida , Adolescente , Adulto , Dengue/epidemiologia , Feminino , Humanos , Masculino , Peru/epidemiologia , Adulto Jovem
4.
PLoS Comput Biol ; 16(4): e1007743, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32310958

RESUMO

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.


Assuntos
Biologia Computacional/métodos , Dengue/prevenção & controle , Controle de Mosquitos/métodos , Aedes/fisiologia , Animais , Simulação por Computador , Dengue/epidemiologia , Dengue/transmissão , Surtos de Doenças , Humanos , Incidência , Inseticidas , Modelos Teóricos , Mosquitos Vetores , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/transmissão
5.
PLoS Negl Trop Dis ; 14(4): e0008097, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32275653

RESUMO

Dengue is one of the most important vector-borne diseases, resulting in an estimated hundreds of millions of infections annually throughout the tropics. Control of dengue is heavily dependent upon control of its primary mosquito vector, Aedes aegypti. Innovative interventions that are effective at targeting the adult stage of the mosquito are needed to increase the options for effective control. The use of insecticide-treated curtains (ITCs) has previously been shown to significantly reduce the abundance of Ae. aegypti in and around homes, but the impact of ITCs on dengue virus (DENV) transmission has not been rigorously quantified. A parallel arm cluster-randomized controlled trial was conducted in Iquitos, Peru to quantify the impact of ITCs on DENV seroconversion as measured through plaque-reduction neutralization tests. Seroconversion data showed that individuals living in the clusters that received ITCs were at greater risk to seroconverting to DENV, with an average seroconversion rate of 50.6 per 100 person-years (PY) (CI: 29.9-71.9), while those in the control arm had an average seroconversion rate of 37.4 per 100 PY (CI: 15.2-51.7). ITCs lost their insecticidal efficacy within 6 months of deployment, necessitating re-treatment with insecticide. Entomological indicators did not show statistically significant differences between ITC and non-ITC clusters. It's unclear how the lack of protective efficacy reported here is attributable to simple failure of the intervention to protect against Ae. aegypti bites, or the presence of a faulty intervention during much of the follow-up period. The higher risk of dengue seroconversion that was detected in the ITC clusters may have arisen due to a false sense of security that inadvertently led to less routine protective behaviors on the part of households that received the ITCs. Our study provides important lessons learned for conducting cluster randomized trials for vector control interventions against Aedes-transmitted virus infections.


Assuntos
Dengue/prevenção & controle , Dengue/transmissão , Transmissão de Doença Infecciosa/prevenção & controle , Mosquiteiros Tratados com Inseticida , Controle de Mosquitos/métodos , Adolescente , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Vírus da Dengue/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Neutralização , Peru , Soroconversão , Resultado do Tratamento , Adulto Jovem
6.
Emerg Infect Dis ; 26(4): 731-737, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32186493

RESUMO

During April-June 2014 in a malaria-endemic rural community close to the city of Iquitos in Peru, we detected evidence of Guaroa virus (GROV) infection in 14 febrile persons, of whom 6 also had evidence of Plasmodium vivax malaria. Cases were discovered through a long-term febrile illness surveillance network at local participating health facilities. GROV cases were identified by using a combination of seroconversion and virus isolation, and malaria was diagnosed by thick smear and PCR. GROV mono-infections manifested as nonspecific febrile illness and were clinically indistinguishable from GROV and P. vivax co-infections. This cluster of cases highlights the potential for GROV transmission in the rural Peruvian Amazon, particularly in areas where malaria is endemic. Further study of similar areas of the Amazon may provide insights into the extent of GROV transmission in the Amazon basin.

7.
PLoS Negl Trop Dis ; 13(10): e0007773, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31658252

RESUMO

In 2012, the U.S. Defense Threat Reduction Agency Joint Science and Technology Office initiated a program to develop novel point-of-need diagnostic devices for surveillance of emerging infectious diseases including dengue, malaria, plague, and melioidosis. Prior to distribution of devices to observe their correct use among community members in Iquitos, Peru, and Phnom Penh, Cambodia, research was conducted to: 1) assess acceptability of use, including the motivation to use a rapid diagnostic test (RDT) before or instead of seeking care at a health facility, 2) explore comprehension of RDT use instructions, and 3) examine possible strategies for large scale RDT distribution and use at each site. In February 2014, 9 focus group discussions (FGD) with community members and 5 FGD with health professionals were conducted in Iquitos, and 9 FGD with community members and 9 in-depth interviews with health professionals in Phnom Penh. In both places, participants agreed to use the device themselves (involving finger prick) or could identify someone who could do so in their home or neighborhood. The main incentive to RDT use in both sites was the ability for device results to be used for care facilitation (post confirmatory tests), specifically reduced wait times to be seen or obtain a diagnosis. Comprehension of RDT use instructions was assessed in Iquitos by asking some participants to apply the device to research team members; after watching a short video, most steps were done correctly. In Phnom Penh, participants were asked to describe each step after reading the instructions; they struggled with comprehension. Health professionals' main concerns in both sites were their community's ability to accurately use the test, handle complicated instructions, and safety (i.e., disposal of lancets). Health system structure and ability to use home diagnostic devices varied in the two disease endemic sites, with substantial challenges in each, suggesting the need for different strategies for RDT large scale community use, and illustrating the value of formative research before deployment of novel technologies.


Assuntos
Testes Diagnósticos de Rotina/métodos , Testes Diagnósticos de Rotina/normas , Pessoal de Saúde/educação , Adolescente , Adulto , Camboja , Dengue/diagnóstico , Educação/métodos , Feminino , Grupos Focais , Instalações de Saúde , Conhecimentos, Atitudes e Prática em Saúde , Pesquisa sobre Serviços de Saúde , Humanos , Malária/diagnóstico , Masculino , Melioidose/diagnóstico , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Peru , Peste/diagnóstico , Manejo de Espécimes/métodos , Adulto Jovem
8.
PLoS Negl Trop Dis ; 13(9): e0007756, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31545804

RESUMO

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.


Assuntos
Dengue/epidemiologia , Comportamento de Doença , Locomoção , Adolescente , Vírus da Dengue/isolamento & purificação , Feminino , Febre , Humanos , Masculino , Peru/epidemiologia , Estudos Retrospectivos , Inquéritos e Questionários
9.
PLoS Negl Trop Dis ; 13(9): e0007552, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31532762

RESUMO

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


Assuntos
Aedes/genética , Mosquitos Vetores/genética , Aedes/fisiologia , Distribuição Animal , Animais , Fluxo Gênico , Genética Populacional , Atividades Humanas , Repetições de Microssatélites , Mosquitos Vetores/fisiologia , Peru , Navios
10.
PLoS Negl Trop Dis ; 13(7): e0007482, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31260441

RESUMO

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


Assuntos
Análise Custo-Benefício , Vacinas contra Dengue/economia , Dengue/prevenção & controle , Programas de Rastreamento/economia , Saúde Pública/economia , Vacinação/economia , Anticorpos Neutralizantes , Anticorpos Antivirais/sangue , Simulação por Computador , Dengue/economia , Humanos , Testes Sorológicos/economia , Fatores de Tempo , Vacinação/efeitos adversos , Cobertura Vacinal/estatística & dados numéricos , Organização Mundial da Saúde
11.
PLoS Negl Trop Dis ; 13(5): e0007255, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31145744

RESUMO

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.


Assuntos
Aedes/fisiologia , Controle de Mosquitos/métodos , Mosquitos Vetores/fisiologia , Aedes/efeitos dos fármacos , Aedes/crescimento & desenvolvimento , Animais , Cidades , Feminino , Inseticidas/farmacologia , Masculino , Mosquitos Vetores/efeitos dos fármacos , Mosquitos Vetores/crescimento & desenvolvimento , Peru , Dinâmica Populacional , Estações do Ano , Análise Espaço-Temporal
12.
PLoS Comput Biol ; 15(3): e1006710, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30893294

RESUMO

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.


Assuntos
Dengue/prevenção & controle , Dengue/transmissão , Análise de Sistemas , Incerteza , Vacinas Virais/administração & dosagem , Calibragem , Criança , Simulação por Computador , Humanos , Peru
13.
PLoS Negl Trop Dis ; 13(2): e0007090, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30742621

RESUMO

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


Assuntos
Aedes/fisiologia , Vírus da Dengue/fisiologia , Dengue/virologia , Mosquitos Vetores/fisiologia , Adolescente , Adulto , Aedes/virologia , Idoso , Animais , Dengue/transmissão , Comportamento Alimentar , Feminino , Grupos Focais , Humanos , Consentimento Livre e Esclarecido , Mordeduras e Picadas de Insetos , Masculino , Pessoa de Meia-Idade , Mosquitos Vetores/virologia , Peru , Adulto Jovem
14.
PLoS Negl Trop Dis ; 13(2): e0007116, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30753180

RESUMO

BACKGROUND: Transmission of dengue virus (DENV) from humans to mosquitoes represents a critical component of dengue epidemiology. Examinations of this process have generally been hampered by a lack of methods that adequately represent natural acquisition of DENV by mosquitoes from humans. In this study, we assessed artificial and natural blood feeding methods based on rates of DENV infection and dissemination within mosquitoes for use in a field-based epidemiological cohort study in Iquitos, Peru. METHODOLOGY/PRINCIPAL FINDINGS: Our study was implemented, stepwise, between 2011 and 2015. Participants who were 5 years and older with 5 or fewer days of fever were enrolled from ongoing clinic- and neighborhood-based studies on dengue in Iquitos. Wild type, laboratory-reared Aedes aegypti were fed directly on febrile individuals or on blood collected from participants that was either untreated or treated with EDTA. Mosquitoes were tested after approximately 14 days of extrinsic incubation for DENV infection and dissemination. A total of 58 participants, with viremias ranging from 1.3 × 10(2) to 2.9 × 10(6) focus-forming units per mL of serum, participated in one or more feeding methods. DENV infection and dissemination rates were not significantly different following direct and indirect-EDTA feeding; however, they were significantly lower for mosquitoes that fed indirectly on blood with no additive. Relative to direct feeding, infection rates showed greater variation following indirect-EDTA than indirect-no additive feeding. Dissemination rates were similar across all feeding methods. No differences were detected in DENV infection or dissemination rates in mosquitoes fed directly on participants with different dengue illness severity. CONCLUSIONS/SIGNIFICANCE: Our study demonstrates the feasibility of using direct and indirect feeding methods for field-based studies on vector competence. Direct mosquito feeding is preferable in terms of logistical ease, biosecurity, and reliability.


Assuntos
Aedes/virologia , Vírus da Dengue/fisiologia , Dengue/virologia , Mosquitos Vetores/virologia , Adolescente , Adulto , Aedes/fisiologia , Idoso , Animais , Dengue/transmissão , Comportamento Alimentar , Feminino , Humanos , Consentimento Livre e Esclarecido , Mordeduras e Picadas de Insetos , Pessoa de Meia-Idade , Mosquitos Vetores/fisiologia , Adulto Jovem
15.
PLoS One ; 14(1): e0210041, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30682037

RESUMO

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


Assuntos
Ensaios Clínicos Fase III como Assunto , Vacinas contra Dengue/imunologia , Vírus da Dengue/imunologia , Dengue/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Adolescente , Adulto , Viés , Criança , Pré-Escolar , Dengue/tratamento farmacológico , Dengue/virologia , Vacinas contra Dengue/administração & dosagem , Vírus da Dengue/efeitos dos fármacos , Vírus da Dengue/fisiologia , Humanos , Peru , Projetos de Pesquisa , Resultado do Tratamento , Viremia/tratamento farmacológico , Viremia/virologia , Adulto Jovem
16.
PLoS Negl Trop Dis ; 12(8): e0006708, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30161130

RESUMO

Zika virus was reported in the rainforest city of Iquitos, Peru in 2016. The potential associations between Zika and fetal neurological disorders were reported extensively in the media regarding neighboring Brazil, and led to great concern about the impact Zika could have on people's health in Iquitos when it arrived. The aim of this study was to explore the knowledge, attitudes, and preventative practices related to Zika virus and its transmission among women of childbearing age in Iquitos, Peru. Six focus group discussions with 46 women of ages 20-35 from an Iquitos district with confirmed Zika cases were conducted to explore: 1) knowledge of Zika transmission, its symptoms, and treatment, 2) attitudes regarding Zika, including perceptions of risk for and severity of Zika, and 3) preventative practices, including awareness of health promotion activities. Participants were knowledgeable about Zika symptoms and knew it was transmitted by mosquitoes, and about half had heard about the association between Zika and microcephaly, but most lacked knowledge about the associated neurological disorders in adults, its sexual transmission, and ways to prevent infection. They expressed concern for pregnant women exposed to the virus and the impact on the fetus. Participants felt at risk of contracting the Zika virus, yet had not changed preventive practices, possibly in part because their perception of the severity of this disease was low. This study reveals knowledge gaps that could be addressed via health promotion messages that might improve prevention practices to help community members protect themselves from Zika virus during this outbreak.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/prevenção & controle , Zika virus , Adulto , Feminino , Grupos Focais , Humanos , Peru , Gravidez , Fatores de Risco , Adulto Jovem , Infecção por Zika virus/transmissão
17.
Parasit Vectors ; 11(1): 365, 2018 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-29941038

RESUMO

BACKGROUND: Insecticides used against Aedes aegypti and other disease vectors can elicit a multitude of dose-dependent effects on behavioral and bionomic traits. Estimating the potential epidemiological impact of a product requires thorough understanding of these effects and their interplay at different dosages. Volatile spatial repellent (SR) products come with an additional layer of complexity due to the potential for altered movement of affected mosquitoes and diffusion of volatile particles of the product beyond the treated house. Here, we propose a paired experimental design and statistical inference framework for estimating these nuanced effects of volatile SRs. METHOD: We fitted a continuous-time Markov chain model in a Bayesian framework to data on marked mosquitoes released in interconnected experimental huts conducted in Iquitos, Peru. We estimated the effects of two dosages of transfluthrin on Ae. aegypti behaviors associated with human-vector contact: repellency, exiting and knockdown in the treated space and in connected, adjacent huts. We validated the framework using simulated data. RESULTS: The odds of a female Ae. aegypti being repelled, and thus prevented from entering a treated hut (HT), increased at both dosages (low dosage: odds = 1.64, 95% highest density interval (HDI) = 1.30-2.09; high dosage: odds = 1.35, HDI = 1.04-1.67). The relative risk of exiting from the treated hut was reduced (low: RR = 0.70, HDI = 0.62-1.09; high: RR = 0.70, HDI = 0.40-1.06), with this effect carrying over to untreated spaces two huts away from the treated hut (H2) (low: RR = 0.79, HDI = 0.59-1.01; high: RR = 0.66, HDI = 0.50-0.87). Knockdown rates were increased in both treated and downstream huts, particularly under high dosage (HT: RR = 8.37, HDI = 2.11-17.35; H1: RR = 1.39, HDI = 0.52-2.69; H2: RR = 2.22, HDI = 0.96-3.86). CONCLUSIONS: Our framework is effective at elucidating multiple effects of volatile chemicals used in SR products, as well as their downstream effects. For the examined formulations of transfluthrin, we found notable dose-dependent effects on repellency, movement and knockdown that carry over to adjacent, untreated spaces.


Assuntos
Aedes/efeitos dos fármacos , Habitação , Repelentes de Insetos/farmacologia , Inseticidas/farmacologia , Controle de Mosquitos , Animais , Teorema de Bayes , Ciclopropanos/farmacologia , Dengue/prevenção & controle , Feminino , Fluorbenzenos/farmacologia , Humanos , Repelentes de Insetos/química , Inseticidas/química , Cadeias de Markov , Mosquitos Vetores/efeitos dos fármacos , Volatilização , Infecção por Zika virus/prevenção & controle
18.
PLoS Pathog ; 14(5): e1006965, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29723307

RESUMO

Despite estimates that, each year, as many as 300 million dengue virus (DENV) infections result in either no perceptible symptoms (asymptomatic) or symptoms that are sufficiently mild to go undetected by surveillance systems (inapparent), it has been assumed that these infections contribute little to onward transmission. However, recent blood-feeding experiments with Aedes aegypti mosquitoes showed that people with asymptomatic and pre-symptomatic DENV infections are capable of infecting mosquitoes. To place those findings into context, we used models of within-host viral dynamics and human demographic projections to (1) quantify the net infectiousness of individuals across the spectrum of DENV infection severity and (2) estimate the fraction of transmission attributable to people with different severities of disease. Our results indicate that net infectiousness of people with asymptomatic infections is 80% (median) that of people with apparent or inapparent symptomatic infections (95% credible interval (CI): 0-146%). Due to their numerical prominence in the infectious reservoir, clinically inapparent infections in total could account for 84% (CI: 82-86%) of DENV transmission. Of infections that ultimately result in any level of symptoms, we estimate that 24% (95% CI: 0-79%) of onward transmission results from mosquitoes biting individuals during the pre-symptomatic phase of their infection. Only 1% (95% CI: 0.8-1.1%) of DENV transmission is attributable to people with clinically detected infections after they have developed symptoms. These findings emphasize the need to (1) reorient current practices for outbreak response to adoption of pre-emptive strategies that account for contributions of undetected infections and (2) apply methodologies that account for undetected infections in surveillance programs, when assessing intervention impact, and when modeling mosquito-borne virus transmission.


Assuntos
Dengue/transmissão , Aedes/virologia , Animais , Dengue/diagnóstico , Dengue/virologia , Vírus da Dengue/patogenicidade , Reservatórios de Doenças/virologia , Interações Hospedeiro-Patógeno , Humanos , Modelos Biológicos , Mosquitos Vetores/virologia , Viremia/diagnóstico , Viremia/transmissão , Viremia/virologia
19.
PLoS Negl Trop Dis ; 12(4): e0006378, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29624581

RESUMO

BACKGROUND: Aedes aegypti is a primary vector of dengue, chikungunya, Zika, and urban yellow fever viruses. Indoor, ultra low volume (ULV) space spraying with pyrethroid insecticides is the main approach used for Ae. aegypti emergency control in many countries. Given the widespread use of this method, the lack of large-scale experiments or detailed evaluations of municipal spray programs is problematic. METHODOLOGY/PRINCIPAL FINDINGS: Two experimental evaluations of non-residual, indoor ULV pyrethroid spraying were conducted in Iquitos, Peru. In each, a central sprayed sector was surrounded by an unsprayed buffer sector. In 2013, spray and buffer sectors included 398 and 765 houses, respectively. Spraying reduced the mean number of adults captured per house by ~83 percent relative to the pre-spray baseline survey. In the 2014 experiment, sprayed and buffer sectors included 1,117 and 1,049 houses, respectively. Here, the sprayed sector's number of adults per house was reduced ~64 percent relative to baseline. Parity surveys in the sprayed sector during the 2014 spray period indicated an increase in the proportion of very young females. We also evaluated impacts of a 2014 citywide spray program by the local Ministry of Health, which reduced adult populations by ~60 percent. In all cases, adult densities returned to near-baseline levels within one month. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that densities of adult Ae. aegypti can be reduced by experimental and municipal spraying programs. The finding that adult densities return to approximately pre-spray densities in less than a month is similar to results from previous, smaller scale experiments. Our results demonstrate that ULV spraying is best viewed as having a short-term entomological effect. The epidemiological impact of ULV spraying will need evaluation in future trials that measure capacity of insecticide spraying to reduce human infection or disease.


Assuntos
Aedes/efeitos dos fármacos , Insetos Vetores/efeitos dos fármacos , Inseticidas/toxicidade , Controle de Mosquitos/métodos , Aedes/fisiologia , Animais , Feminino , Insetos Vetores/fisiologia , Inseticidas/análise , Masculino , Peru , Piretrinas/análise , Piretrinas/toxicidade
20.
BMC Public Health ; 17(Suppl 1): 410, 2017 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-28699548

RESUMO

We discuss two ethical issues raised by Camino Verde, a 2011-2012 cluster-randomised controlled trial in Mexico and Nicaragua, that reduced dengue risk though community mobilisation. The issues arise from the approach adopted by the intervention, one called Socialisation of Evidence for Participatory Action. Community volunteer teams informed householders of evidence about dengue, its costs and the life-cycle of Aedes aegypti mosquitoes, while showing them the mosquito larvae in their own water receptacles, without prescribing solutions. Each community responded in an informed manner but on its own terms. The approach involves partnerships with communities, presenting evidence in a way that brings conflicting views and interests to the surface and encourages communities themselves to deal with the resulting tensions.One such tension is that between individual and community rights. This tension can be resolved creatively in concrete day-to-day circumstances provided those seeking to persuade their neighbours to join in efforts to benefit community health do so in an atmosphere of dialogue and with respect for personal autonomy.A second tension arises between researchers' responsibilities for ethical conduct of research and community autonomy in the conduct of an intervention. An ethic of respect for individual and community autonomy must infuse community intervention research from its inception, because as researchers succeed in fostering community self-determination their direct influence in ethical matters diminishes. TRIAL REGISTRATION: ISRCTN 27581154.


Assuntos
Temas Bioéticos , Participação da Comunidade , Dengue/prevenção & controle , Ética em Pesquisa , Controle de Mosquitos/métodos , Poder Psicológico , Características de Residência , Adulto , Aedes , Animais , Criança , Educação em Saúde , Humanos , México , Nicarágua , Pesquisa , Voluntários , Abastecimento de Água
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