Direct mosquito feedings on dengue-2 virus-infected people reveal dynamics of human infectiousness.

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.

Inapparent infections shape the transmission heterogeneity of dengue.

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.

Quantifying heterogeneities in arbovirus transmission: Description of the rationale and methodology for a prospective longitudinal study of dengue and Zika virus transmission in Iquitos, Peru (2014-2019).

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.

Stakeholder engagement in eight comparative effectiveness trials in African Americans and Latinos with asthma.

BACKGROUND: The effects of stakeholder engagement, particularly in comparative effectiveness trials, have not been widely reported. In 2014, eight comparative effectiveness studies targeting African Americans and Hispanics/Latinos with uncontrolled asthma were funded by the Patient-Centered Outcomes Research Institute (PCORI) as part of its Addressing Disparities Program. Awardees were required to meaningfully involve patients and other stakeholders. Using specific examples, we describe how these stakeholders substantially changed the research protocols and in other ways participated meaningfully as full partners in the development and conduct of the eight studies. METHODS: Using the method content analysis of cases, we identified themes regarding the types of stakeholders, methods of engagement, input from the stakeholders, changes made to the research protocols and processes, and perceived benefits and challenges of the engagement process. We used summaries from meetings of the eight teams, results from an engagement survey, and the final research reports as our data source to obtain detailed information. The descriptive data were assessed by multiple reviewers using inductive and deductive qualitative methods and discussed in the context of engagement literature. RESULTS: Stakeholders participated in the planning, conduct, and dissemination phases of all eight asthma studies. All the studies included clinicians and community representatives as stakeholders. Other stakeholders included patients with asthma, their caregivers, advocacy organizations, and health-system representatives. Engagement was primarily by participation in advisory boards, although six of the eight studies (75%) also utilized focus groups and one-on-one interviews. Difficulty finding a time and location to meet was the most reported challenge to engagement, noted by four of the eight teams (50%). Other reported challenges and barriers to engagement included recruitment of stakeholders, varying levels of enthusiasm among stakeholders, controlling power dynamics, and ensuring that stakeholder involvement was reflected and had true influence on the project. CONCLUSION: Engagement-driven modifications led to specific changes in study design and conduct that were felt to have increased enrollment and the general level of trust and support of the targeted communities. The level of interaction described, between investigators and stakeholders in each study and between investigator-stakeholder groups, is-we believe-unprecedented and may provide useful guidance for other studies seeking to improve the effectiveness of community-driven research.

The goal of comparative clinical effectiveness research is to compare healthcare options and learn which work best for patients depending on their preferences and circumstances. Research efforts can be more effective when researchers engage stakeholders, such as patients, healthcare providers, and other members of the community­especially those communities or groups targeted by the planned research. Stakeholders can give their input throughout the research process to make sure the study will address questions and concerns that are most important and useful for participants. In 2014, the PCORI funded eight research studies that evaluated various ways to help African Americans and Hispanics/Latinos with poorly controlled asthma. These groups are underrepresented in asthma research but have higher rates of and more severe asthma for reasons that are poorly understood. The goal of this report is to show how stakeholders­including patients with asthma from these underrepresented groups, healthcare providers who care for patients with asthma, key representatives from the communities and others­participated as full partners in the eight studies and helped to improve the overall quality of the research and the relationship between the researchers and the community.

Two-year outcomes of Faith in Action/Fe en Acción: a randomized controlled trial of physical activity promotion in Latinas.

BACKGROUND: Latina women are less likely to report engaging in leisure-time physical activity (PA) than non-Latina white women. This study evaluated the 24-month impact of a faith-based PA intervention targeting Latinas. METHODS: The study is a cluster randomized controlled trial of a PA intervention or cancer screening comparison condition, with churches as the randomization unit. A total of 436 Latinas (aged 18-65 years) from 16 churches who engaged in low levels of self-report and accelerometer-based PA were enrolled. The experimental condition was a 24-month PA intervention, with in-person classes, social support, and environmental changes, led by community health workers (i.e., promotoras). At baseline, 12-, and 24 months, we assessed changes in accelerometer-based and self-reported moderate to vigorous physical activity (MVPA; primary outcomes). Secondary outcomes were light intensity activity, sedentary time, body mass index (BMI), and waist circumference. RESULTS: After adjusting for sociodemographic factors, a mixed effects analysis found significant increases in self-reported leisure time MVPA (p < 0.005) and marginal increases in accelerometer-assessed MVPA (p < 0.08) 24 months post-baseline in the intervention compared to the attention-control condition. Data showed significant associations between PA class attendance and engaging in MVPA as assessed by self-report and accelerometry. No significant changes were found for light activity, sedentary time, BMI, or waist circumference. CONCLUSIONS: Participants who attended the PA classes at least once a month engaged in significantly higher MVPA compared to those who did not. Maximizing engagement and maintenance strategies to enhance PA maintenance could contribute to important long-term health benefits. TRIAL REGISTRATION: NCT01776632 , Registered March 18, 2011.

Predictors and Effects of Participation in Peer Support: A Prospective Structural Equation Modeling Analysis.

BACKGROUND: Peer support provides varied health benefits, but how it achieves these benefits is not well understood. PURPOSE: Examine a) predictors of participation in peer support interventions for diabetes management, and b) relationship between participation and glycemic control. METHODS: Seven peer support interventions funded through Peers for Progress provided pre/post data on 1,746 participants' glycemic control (hemoglobin A1c), contacts with peer supporters as an indicator of participation, health literacy, availability/satisfaction with support for diabetes management from family and clinical team, quality of life (EQ-Index), diabetes distress, depression (PHQ-8), BMI, gender, age, education, and years with diabetes. RESULTS: Structural equation modeling indicated a) lower levels of available support for diabetes management, higher depression scores, and older age predicted more contacts with peer supporters, and b) more contacts predicted lower levels of final HbA1c as did lower baseline levels of BMI and diabetes distress and fewer years living with diabetes. Parallel effects of contacts on HbA1c, although not statistically significant, were observed among those with baseline HbA1c values > 7.5% or > 9%. Additionally, no, low, moderate, and high contacts showed a significant linear, dose-response relationship with final HbA1c. Baseline and covariate-adjusted, final HbA1c was 8.18% versus 7.86% for those with no versus high contacts. CONCLUSIONS: Peer support reached/benefitted those at greater disadvantage. Less social support for dealing with diabetes and higher PHQ-8 scores predicted greater participation in peer support. Participation in turn predicted lower HbA1c across levels of baseline HbA1c, and in a dose-response relationship across levels of participation.

Body image and disordered eating behaviors in Hispanic/Latino Youth: Findings from the Hispanic Community Health Study/Study of Latino Youth.

BACKGROUND: Prevalence of certain disordered eating behaviors is higher among Hispanic youth compared to non-Hispanics. Understanding the role of body image and social attitudes towards weight in disordered eating may inform treatment in Hispanic youth. METHODS: We analyzed data from the Hispanic Community Health Study/Study of Latino Youth (SOL Youth). Our sample included 1,463 children aged 8-16 years from four sites (Bronx, Chicago, Miami, San Diego) assessed in 2011-2014. Body image discrepancy score was calculated as the difference between perceived ideal body image and actual body image using two numbered visual graphs: adolescent (n = 728) or child (n = 735), each with slightly different scales. Questionnaires measured influences from social attitudes toward weight and disordered eating behaviors. Three disordered eating behaviors (dieting, overeating, and compensatory behaviors) were analyzed as the dependent variable. Logistic regression models adjusted for age, sex, acculturative stress, and field center to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI). RESULTS: Mean body image discrepancy score was -0.79 for adolescents (SE = 0.08) and -0.50 for children (SE = 0.05), with a negative score signifying a perceived actual body image larger than their ideal. Body image discrepancy was strongly associated with dieting (dieting ≥5 times/year aOR = 0.64, 95% CI 0.53, 0.77) and compensatory behaviors (aOR = 0.65, 95% CI 0.50, 0.85) among adolescents, and was strongly associated with overeating among children (aOR = 0.74, 95% CI 0.61, 0.91). Significant associations were not observed with social attitudes towards weight. CONCLUSIONS: Associations observed with body image discrepancy and disordered eating behaviors can inform interventions in Hispanic/Latino youth, which should consider acculturative stress.

The El Valor de Nuestra Salud clustered randomized controlled trial store-based intervention to promote fruit and vegetable purchasing and consumption.

BACKGROUND: Modifying the environment to promote healthy foods is a population-based approach for improving diet. This study evaluated the outcome effectiveness of a food store intervention that used structural and social change strategies to promote fruits and vegetables. It was hypothesized that intervention versus control store customers would improve their consumption of fruits and vegetables at 6 months. TRIAL DESIGN: Clustered randomized controlled trial METHODS: Sixteen pair-matched stores were randomized to an intervention or wait-list control condition. With the research team's support, intervention stores modified the availability, accessibility, and promotion of fruits and vegetables, including augmenting produce displays within the store and building employees' capacity to place and promote fruits and vegetables throughout the store (Phase 1), followed by the delivery of a customer-directed marketing campaign for 6 months (Phase 2). From months 7 to 12, stores were encouraged to maintain strategies on their own (Phase 3). Customer-reported daily fruit and vegetable consumption (cups/day) were collected by blinded research assistants at three time-points (baseline, 6 months and 12 months post-baseline) from 369 participating customers (an average of 23/store). Secondary outcomes included customer-reported fruit and vegetable purchasing and other behaviors. RESULTS: The study retained the 16 stores and most customers at 6 (91%) and 12 (89%) months. Although significant differences were not observed in the overall sample for vegetable consumption, male customers of intervention versus control stores consumed significantly more fruit daily at 6 months [mean (standard deviation) cups at baseline and six months; intervention: 1.6 (1.5) to 1.6 (1.5) vs. control: 1.4 (1.2) to 1.1 (0.8)]. However, this difference was not observed at 12 months, or among females. There was an overall increase in dollars spent at the targeted store in the intervention versus control condition among male versus female customers at 6 months; however, no change was observed in the percent of dollars spent on fruits and vegetables at the targeted store. Frequency of shopping at the targeted store did not modify intervention effects. CONCLUSIONS: Structural and social change interventions can modify customers' behavior in the short-term. Future research should consider methods for achieving longer-term changes, and potential generalizability to other products (e.g., energy-dense sweet and savory products). TRIAL REGISTRATION: NCT01475526.

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

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.

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

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.

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

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.

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

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.

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

[This corrects the article DOI: 10.1371/journal.pntd.0007756.].

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

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.

Examining Mexican-Heritage Mothers' Perceptions of Their Children's Weight: Comparison of Silhouette and Categorical Survey Methods.

Background: Failure to recognize children's overweight status by parents may contribute to children's risk for obesity. We examined two methods of measuring mothers' perceptions of children's weight and factors associated with weight perception inaccuracy. Methods: Cross-sectional analyses of clinical and self-report data from 287 Mexican-heritage mother-child dyads. Mothers identified their child's weight category using a scale (e.g., "normal/overweight/obese") and a visual silhouette scale (11 child gender-specific weight-varying images). Children's height and weight were measured to calculate body mass index (BMI). Chi-square tests examined associations between categorical, silhouette, and BMI percentile categories of children's weight. Bivariate logistic regression analyses examined factors associated with mothers' inaccuracy of their children's weight. Results: Only 13% of mothers accurately classified their child as obese using the categorical scale, while 78% accurately classified their child as obese using the silhouette scale. Mothers were more likely to underestimate their child's weight using BMI categories (62%) compared to using the silhouette scale (23%). Predictors of mothers' underestimation using the categorical method were child sex [female] (adjusted odds ratio [AOR] = 1.99; 95% CI: 1.02-3.86), child age [younger age] (AOR = 10.39; 95% CI: 4.16-25.92 for ages 5-6 years), and mother's weight status (overweight AOR = 2.99; 95% CI: 1.05-8.51; obese AOR = 5.19; 95% CI: 1.89-14.18). Child BMI was the only predictor of mothers' overestimation (AOR = 0.89; 95% CI: 0.85-0.94) using the silhouette method. Conclusions: Using silhouette scales to identify children's body weight may be a more accurate tool for clinicians and interventionists to activate parents' awareness of unhealthy weight in children compared to using traditional categorical weight-labeling methods.

Evaluation of Store Environment Changes of an In-Store Intervention to Promote Fruits and Vegetables in Latino/Hispanic-Focused Food Stores.

Implementing interventions that manipulate food store environments are one potential strategy for improving dietary behaviors. The present study evaluated intervention effects, from the El Valor de Nuestra Salud (The Value of Our Health) study, on in-store environmental changes within Latino/Hispanic-focused food stores (tiendas). Sixteen tiendas were randomly assigned to either: a six-month structural and social food store intervention or a wait-list control condition. Store-level environmental measures of product availability, placement, and promotion were assessed monthly from baseline through six-months post-baseline using store audits. Linear mixed effects models tested for condition-by-time interactions in store-level environmental measures. Results demonstrated that the intervention was successful at increasing the total number of fruit and vegetable (FV) promotions (p < 0.001) and the number of FV promotions outside the produce department (p < 0.001) among tiendas in the intervention versus control condition. No changes in product availability or placement were observed. Results suggests changing the marketing mix element of promotions within small stores is measurable and feasible in an in-store intervention. Difficulties in capturing changes in product availability and placement may be due to intervention implementation methods chosen by tiendas. It is important to build upon the lessons learned from these types of interventions to disseminate evidence-based in-store interventions.

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

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.

Immunopathologic Effects of Prednisolone and Cyclosporine A on Feline Immunodeficiency Virus Replication and Persistence.

Feline immunodeficiency virus (FIV) induces opportunistic disease in chronically infected cats, and both prednisolone and cyclosporine A (CsA) are clinically used to treat complications such as lymphoma and stomatitis. However, the impact of these compounds on FIV infection are still unknown and understanding immunomodulatory effects on FIV replication and persistence is critical to guide safe and effective therapies. To determine the immunologic and virologic effects of prednisolone and CsA during FIV infection, FIV-positive cats were administered immunosuppressive doses of prednisolone (2 mg/kg) or CsA (5 mg/kg). Both prednisolone and CsA induced acute and transient increases in FIV DNA and RNA loads as detected by quantitative PCR. Changes in the proportion of lymphocyte immunophenotypes were also observed between FIV-infected and naïve cats treated with CsA and prednisolone, and both treatments caused acute increases in CD4+ lymphocytes that correlated with increased FIV RNA. CsA and prednisolone also produced alterations in cytokine expression that favored a shift toward a Th2 response. Pre-treatment with CsA slightly enhanced the efficacy of antiretroviral therapy but did not enhance clearance of FIV. Results highlight the potential for drug-induced perturbation of FIV infection and underscore the need for more information regarding immunopathologic consequences of therapeutic agents on concurrent viral infections.

A unique variant of lymphocytic choriomeningitis virus that induces pheromone binding protein MUP: Critical role for CTL.

Lymphocytic choriomeningitis virus (LCMV) WE variant 2.2 (v2.2) generated a high level of the major mouse urinary protein: MUP. Mice infected with LCMV WE v54, which differed from v2.2 by a single amino acid in the viral glycoprotein, failed to generate MUP above baseline levels found in uninfected controls. Variant 54 bound at 2.5 logs higher affinity to the LCMV receptor α-dystroglycan (α-DG) than v2.2 and entered α-DG-expressing but not α-DG-null cells. Variant 2.2 infected both α-DG-null or -expressing cells. Variant 54 infected more dendritic cells, generated a negligible CD8 T cell response, and caused a persistent infection, while v2.2 generated cytotoxic T lymphocytes (CTLs) and cleared virus within 10 days. By 20 days postinfection and through the 80-day observation period, significantly higher amounts of MUP were found in v2.2-infected mice. Production of MUP was dependent on virus-specific CTL as deletion of such cells aborted MUP production. Furthermore, MUP production was not elevated in v2.2 persistently infected mice unless virus was cleared following transfer of virus-specific CTL.

Diet, physical activity, obesity and related cancer risk: strategies to reduce cancer burden in the Americas / Dieta, actividad física, obesidad y riesgo de cáncer: estrategias para reducir la carga del cáncer en las Américas

Abstract: With increased globalization, Latin America is experiencing transitions from traditional lifestyle and dietary practices to those found in higher income countries. Healthy diets, physical activity and optimal body fat can prevent approximately 15% of cancers in low-income and 20% in high-income countries. We discuss links between diet, obesity, physical activity and cancer, emphasizing strategies targeting children to decrease risk of obesity, control obesity-related risk factors, and reduce sedentary lifestyles, as this will have high impact on adult cancer risk. We focus on individual behaviors, economic, cultural and societal changes that may guide future interventions in the Americas.

Resumen: América Latina está experimentando transiciones desde estilos de vida tradicional y prácticas dietéticas a las de países de ingresos altos. Las dietas saludables, la actividad física y la grasa corporal óptima pueden prevenir aproximadamente el 15% de cánceres en países de bajos ingresos y 20% en países de ingresos altos. Discutimos los vínculos entre la dieta, obesidad, actividad física y cáncer; haciendo hincapié en estrategias dirigidas a niños, para disminuir el riesgo de obesidad y reducir la vida sedentaria. Nos enfocamos en comportamientos individuales, cambios económicos, culturales y sociales que pueden guiar futuras intervenciones en las Américas.