Microclimate factors related to dengue virus burden clusters in two endemic towns of Mexico.

In dengue-endemic areas, transmission control is limited by the difficulty of achieving sufficient coverage and sustainability of interventions. To maximize the effectiveness of interventions, areas with higher transmission could be identified and prioritized. The aim was to identify burden clusters of Dengue virus (DENV) infection and evaluate their association with microclimatic factors in two endemic towns from southern Mexico. Information from a prospective population cohort study (2·5 years of follow-up) was used, microclimatic variables were calculated from satellite information, and a cross-sectional design was conducted to evaluate the relationship between the outcome and microclimatic variables in the five surveys. Spatial clustering was observed in specific geographic areas at different periods. Both, land surface temperature (aPR 0·945; IC95% 0·895-0·996) and soil humidity (aPR 3·018; IC95% 1·013-8·994), were independently associated with DENV burden clusters. These findings can help health authorities design focused dengue surveillance and control activities in dengue endemic areas.

House Condition Scoring Scale as a Risk Indicator of Infestation by Aedes in Two Mexican Localities.

Mexico has shown an increase in dengue incidence rates. There are factors related to the location that determine housing infestation by Aedes. This study aimed to determine factors associated with housing infestation by immature forms of Aedes spp. in the dengue endemic localities of Axochiapan and Tepalcingo, Mexico, from 2014 to 2016. A cohort study was carried out. Surveys and inspections of front- and backyards were conducted every 6 months, looking for immature forms of Aedes spp. A house condition scoring scale was developed using three variables (house maintenance, tidiness of the front- and backyards, and shading of the front- and backyards). Multiple and multilevel regression logistic analysis were conducted considering the housing infestation as the outcome and the household characteristics observed 6 months before the outcome as factors; this was adjusted by time (seasonal and cyclical variations of the vector). The infestation oscillated between 5.8% of the houses in the second semester of 2015 and 29.3% in the second semester of 2016. The factors directly associated with housing infestation by Aedes were the house condition score (adjusted odds ratio [aOR]: 1.64; 95% CI: 1.40-1.91) and the previous record of housing infestation (aOR: 2.99; 95% CI: 2.00-4.48). Moreover, the breeding-site elimination done by house residents reduced the housing infestation odds by 81% (95% CI: 25-95%). These factors were independent of the seasonal and cyclical variations of the vector. In conclusion, our findings could help to focalize antivectorial interventions in dengue-endemic regions with similar demographic and socioeconomic characteristics.

First Evidence of Horizontal Transmission by Fecal Shedding of Dengue Virus 4 Among Aedes aegypti Larvae (Diptera: Culicidae) Under Laboratory Conditions.

The transmission pathways of dengue virus (DENV) among mosquitoes are a topic that has gained relevance in recent years because they could explain the maintenance of the virus in the wild independently of the human-mosquito horizontal transmission cycle. In this regard, Aedes aegypti larvae exposed to supernatants of C6/36 cells infected with DENV-4 were evaluated for virus excretion in feces and viability of infection in immature stages (larvae). The results demonstrate that larvae excrete DENV-4 in their feces with the potential to at least infect immature individuals of the same species. A horizontal transmission pathway of larvae-larvae DENV-4 under laboratory conditions is suggested.

Risk Prediction of Death in Inpatient Adults With COVID-19 from Mexico.

Background: There is substantial variation in COVID-19 lethality across countries. In addition, in countries with populations with extreme economic inequalities, such as Mexico, there are regional and local differences in risk factors for COVID-19 death. The goal of this study was to test the hypothesis that the risk of death in Mexican COVID-19 patients was associated with the time between symptom onset and hospitalization and/or with the healthcare site. Also, death prognostic models were developed. Methods: The study included two COVID-19 inpatient cohorts, one prospective and one retrospective from Chiapas, Mexico. Demographic, clinical and laboratory variables were collected, and the diagnosis of SARS-CoV-2 infection was performed using RT-qPCR in samples collected seven days since symptom onset. The 30-day mortality, since symptom onset, was the outcome, and clinical variables at the first 48 hours of hospitalization were independent factors. Multivariate logistic regression analyses were conducted. Results: Of the 392 patients included, 233 died (59.4%). The time between symptom onset and hospitalization, the healthcare site and sex were not related to the 30-day mortality. Three death prognostic models were developed (AUC between 0.726 and 0.807). Age, LDH, AST, and lymphocyte count were included in all models, OSI-WHO Classification (Non-invasive ventilation or high-flow oxygen, and mechanical ventilation with or without organ support/ECMO) and leukocyte count in two models, and diabetes and diarrhea in one model. Conclusion: The population evaluated had underlying deteriorated health before COVID-19 compared with regional and country population. The factors that determine the COVID-19 mortality risk in a relatively healthy population are sex, age and comorbidities. However, as this study shows, when populations have underlying poor health, some of these factors lose their associations with mortality risk, and others become more important.

Comparison of the Impact of Zika and Dengue Virus Infection, and Other Acute Illnesses of Unidentified Origin on Cognitive Functions in a Prospective Cohort in Chiapas Mexico.

Zika has been associated with a variety of severe neurologic manifestations including meningitis and encephalitis. We hypothesized that it may also cause mild to subclinical neurocognitive alterations during acute infection or over the long term. In this observational cohort study, we explored whether Zika cause subclinical or mild neurocognitive alterations, estimate its frequency and duration, and compare it to other acute illnesses in a cohort of people with suspected Zika infection, in the region of Tapachula in Chiapas, Mexico during 2016-2018. We enrolled patients who were at least 12 years old with suspected Zika virus infection and followed them up for 6 months. During each visit participants underwent a complete clinical exam, including a screening test for neurocognitive dysfunction (Montreal Cognitive Assessment score). We enrolled 406 patients [37 with Zika, 73 with dengue and 296 with other acute illnesses of unidentified origin (AIUO)]. We observed a mild and transient impact over cognitive functions in patients with Zika, dengue and with other AIUO. The probability of having an abnormal MoCA score (<26 points) was significantly higher in patients with Zika and AIUO than in those with dengue. Patients with Zika and AIUO had lower memory scores than patients with dengue (Zika vs. Dengue: -0.378, 95% CI-0.678 to -0.078; p = 0.014: Zika vs. AIUO 0.264, 95% CI 0.059, 0.469; p = 0.012). The low memory performance in patients with Zika and AIUO accounts for most of the differences in the overall MoCA score when compared with patients with dengue. Our results show a decrease in cognitive function during acute illness and provides no evidence to support the hypothesis that Zika might cause neurocognitive alterations longer than the period of acute infection or different to other infectious diseases. While effects on memory or perhaps other cognitive functions over the long term are possible, larger studies using more refined tools for neurocognitive functioning assessment are needed to identify these. Trial Registration: NCT02831699.

Universal influenza vaccination: a Mexican Expert Position Paper.

OBJECTIVE: Influenza is a costly disease for the population. It is a cause of seasonal morbidity and mortality, epidemics and pandemics or syndemics. Given the variability of the virus, surveillance systems are implemented in order to update the strains and include them in the annual influenza vaccine. This vaccine is currently recommended in some high-risk groups. However, universal vaccination remains controversial. To evaluate the evidence and describe the position of a panel of experts on the relevance of universal vaccination against influenza virus. MATERIAL AND METHODS: Five clinical questions were asked, whereby a systematic search of the literature in electronic sources and a Delphi panel were carried out. The evidence was analyzed, and recommendations were issued by the experts. RESULTS: The group of experts recommends vaccinating the population starting at six months of age and include people who live with egg protein allergy, with comorbidities (diabetes, obesity, cancer), health workers and pregnant women. CONCLUSIONS: Vaccination, starting with vulnerable groups, is a necessary, ethical and cost-effective strategy. However, expanding the coverage to achieve universal vaccination could reduce the transmission of the disease and its consequences in the population.

OBJETIVO: La influenza es una enfermedad costosa para la población. Es causa de morbimortalidad estacional, epidemias y pandemias o sindemias. Debido a la variabilidad del virus, se implementan sistemas de vigilancia para actualizar las cepas e incluirlas en la vacuna antiinfluenza anual. Actualmente se recomienda esta vacuna en algunos grupos de alto riesgo. Sin embargo, la vacunación universal es aún controvertida. Evaluar la evidencia y describir la posición de un panel de expertos sobre la pertinencia de la vacunación universal contra el virus de influenza. MATERIAL Y MÉTODOS: Se realizaron cinco preguntas clínicas, con las que se realizó una búsqueda sistemática de la literatura en fuentes electrónicas y un panel Delphi. Se analizó la evidencia y se emitieron recomendaciones por los expertos. RESULTADOS: El grupo de expertos recomienda vacunar a la población desde los seis meses de edad e incluir a personas que viven con alergia a la proteína del huevo, con comorbilidades (diabetes, obesidad, cáncer), trabajadores de la salud y embarazadas. CONCLUSIONES: La vacunación, iniciando con los grupos vulnerables, es una estrategia necesaria, ética y costo-efectiva. Sin embargo, extender la cobertura para lograr la vacunación universal podría disminuir la transmisión de la enfermedad y sus consecuencias en la población.

Combine dengue vaccines to optimize effectiveness.

Developing a completely effective and safe dengue vaccine has been a complicated process. Dengvaxia®, by Sanofi-Pasteur, and recently TAK003, by Takeda, have strengths and weaknesses, but they seem to complement each other. In this work, we elaborate a rationale that could be applicable in a combined program of these vaccines for the control of dengue.

When Can One Vaccinate with a Live Vaccine after Wild-Type Dengue Infection?

Recommendations have been issued for vaccinating with the Sanofi Pasteur tetravalent dengue vaccine (CYD-TDV, Dengvaxia®) individuals aged from 9 to 45/60 years old with a prior dengue virus (DENV) infection and living in endemic countries/areas. One question linked to these recommendations is to determine when it is possible to start vaccination after laboratory confirmed wild-type DENV infection, and this question can be relevant to any live vaccine to be used in endemic areas. To address it, we reviewed and discussed the immunological and practical considerations of live vaccination in this context. Firstly, the nature and kinetics of immune responses triggered by primary or secondary DENV infection may positively or negatively impact subsequent live vaccine take and associated clinical benefit, depending on when vaccination is performed after infection. Secondly, regarding practical aspects, the "easiest" situation would correspond to a confirmed acute dengue fever, only requiring knowing when the patient should come back for vaccination. However, in most cases, it will not be possible to firmly establish the actual date of infection and vaccination may have to take place during well-defined periods, regardless of when prior infection occurred. Evidence that informs health authorities and medical practitioners in formulating vaccine policies and implementing vaccine programs is thus needed. The present work reviewed the different elements of the guidance and proposes some key conclusions and recommendations.

Persistence of symptoms in dengue patients: a clinical cohort study.

BACKGROUND: Dengue is commonly considered an acute illness and follows three phases: febrile, critical in some cases and recovery. However, a number of studies have described a continuation of dengue symptoms for weeks or months, extending the recovery phase. Here we evaluate this persistence of dengue symptoms during convalescence. METHODS: Our clinical cohort study included patients who sought medical services 48 to 144 h from the onset of fever at seven hospitals or ambulatory centers in Morelos, Mexico. Seventy-nine laboratory-confirmed dengue patients were followed up regularly using clinic and/or home visits and telephone calls for as long as symptoms persisted or up to 6 mo. RESULTS: In total, 55.7% of patients had dengue-related symptoms 1 mo after the onset of fever; pain and dermatological manifestations were the most common persistent symptoms. Prognostic factors for symptom persistence were: ≥4 d of fever (RR 1.72; 95% CI 1.35 to 2.19), platelet count ≤100 000/mm3 (RR 1.20; 95% CI 1.20 to 2.20), petechiae/bruises (RR 1.97; 95% CI 1.56 to 2.48) and abdominal pain/hepatomegaly (RR 1.79; 95% CI 1.41 to 2.28). CONCLUSIONS: Persistence of dengue symptoms were common in laboratory-confirmed dengue patients. Manifestations related to tissue damage were associated with persistence after 30 d; host characteristics, such as age and health status before infection, were associated with prolonged persistence (>60 d). The burden of dengue may be higher than previously estimated.

Health-Related Quality of Life after Dengue Fever, Morelos, Mexico, 2016-2017.

We adapted the EQ-5D-3L questionnaire and visual analog scale to assess health-related quality of life (HRQOL) and persistent symptoms in 79 patients with laboratory-confirmed dengue in Morelos, Mexico. The lowest HRQOLs were 0.53 and 38.1 (febrile phase). Patients recovered baseline HRQOL in ≈2 months.

Vertical transmission of dengue virus in Aedes aegypti and its role in the epidemiological persistence of dengue in Central and Southern Mexico.

BACKGROUND: Aedes aegypti and Aedes albopictus are the main mosquito species responsible for dengue virus (DENV) transmission to humans in the tropical and subtropical regions of the world. The role of vertical transmission in the epidemiology of dengue and the maintenance of this arbovirus in nature during interepidemic periods remain poorly understood, and DENV vertical transmission could sustain the existence of virus reservoirs within Aedes populations. METHODS: Between April 2011 and October 2012, we monitored vertical transmission of DENV in Ae. aegypti and Ae. albopictus in 9 cities of 4 Mexican states. Aedes eggs were collected in ovitraps, then adults were reared under laboratory conditions and their heads were used to infect C6/36 cells. The presence of flavivirus was detected by immunofluorescence assays (IFA), and DENV infection was confirmed by RT-PCR. RESULTS: About 96% of reared adults were Ae. aegypti and 4.0% were Ae. albopictus. No infection was detected in Ae. albopictus, whereas 54 of 713 (7.8%) of Ae. aegypti pools tested positive. A minimum infection rate (MIR) of 2.52 per 1000 mosquitoes was estimated for Ae. aegypti. DENV-1, DENV-2 & DENV-3 serotypes were detected even during interepidemic periods. CONCLUSIONS: This study reports the evidence of vertical transmission of dengue virus with viral isolation and molecular confirmation in Ae. aegypti eggs collected in four endemic regions of Central and Southern Mexico. Vertical transmission may play a role as a reservoir mechanism during mosquito dormancy in interepidemic periods but with minor participation in transmission during epidemic periods.

TRANSMISSION VERTICALE DU VIRUS DE LA DENGUE CHEZ AEDES AEGYPTI ET SON RÔLE DANS LA PERSISTANCE ÉPIDÉMIOLOGIQUE DE LA DENGUE DANS LE CENTRE ET LE SUD DU MEXIQUE: OBJECTIF: Aedes aegypti et Aedes albopictus sont les principales espèces de moustiques responsables de la transmission du virus de la dengue (DENV) à l'homme dans les régions tropicales et subtropicales du monde. Le rôle de la transmission verticale dans l'épidémiologie de la dengue et le maintien de cet arbovirus dans la nature pendant les périodes d'inter-épidémiques restent mal compris, et la transmission verticale du DENV pourrait maintenir l'existence de réservoirs de virus au sein des populations d'Aedes. Notre objectif était d'évaluer la transmission verticale du DENV au Mexique. MÉTHODES: Entre avril 2011 et octobre 2012, nous avons surveillé la transmission verticale du DENV chez Ae. aegypti et Ae. albopictus dans 9 villes de 4 états mexicains. Les œufs d'Aedes ont été collectés dans des ovitraps, puis les adultes ont été élevés dans des conditions de laboratoire et leur tête a été utilisée pour infecter les cellules C6/36. La présence de flavivirus a été détectée par des tests d'immunofluorescence (IFA) et l'infection par DENV a été confirmée par RT-PCR. RÉSULTATS: 96% des adultes élevés étaient Ae. aegypti et 4,0% étaient Ae. albopictus. Aucune infection n'a été détectée chez Ae. albopictus, alors que 54 des 713 (7,8%) des pools d'Ae. aegypti ont été testés positifs. Un taux d'infection minimum (MIR) de 2,52 pour 1000 moustiques a été estimé pour Ae. aegypti. Les sérotypes DENV-1, DENV-2 et DENV-3 ont été détectés même pendant les périodes inter-épidémiques. CONCLUSIONS: Cette étude rapporte les preuves de transmission verticale du virus de la dengue avec isolement viral et confirmation moléculaire dans les œufs d'Ae. Aegypti collectés dans quatre régions d'endémie du centre et du sud du Mexique. La transmission verticale pourrait jouer un rôle de mécanisme réservoir lors de la dormance des moustiques en période inter-épidémique, mais avec une participation mineure à la transmission en période d'épidémie.

Differential human antibody repertoires following Zika infection and the implications for serodiagnostics and disease outcome.

Zika virus (ZIKV) outbreak in Americas led to extensive efforts to develop vaccines and ZIKV-specific diagnostics. In the current study, we use whole genome phage display library spanning the entire ZIKV genome (ZIKV-GFPDL) for in-depth immune profiling of IgG and IgM antibody repertoires in serum and urine longitudinal samples from individuals acutely infected with ZIKV. We observe a very diverse IgM immune repertoire encompassing the entire ZIKV polyprotein on day 0 in both serum and urine. ZIKV-specific IgG antibodies increase 10-fold between day 0 and day 7 in serum, but not in urine; these are highly focused on prM/E, NS1 and NS2B. Differential antibody affinity maturation is observed against ZIKV structural E protein compared with nonstructural protein NS1. Serum antibody affinity to ZIKV-E protein inversely correlates with ZIKV disease symptoms. Our study provides insight into unlinked evolution of immune response to ZIKV infection and identified unique targets for ZIKV serodiagnostics.

Seroprevalence of dengue in school children in Mexico ages 6-17 years, 2016.

Background: Dengue is the most important arboviral disease in the world. Seroprevalence has been proposed as a marker of endemicity, however, studies are scarce. Methods: We conducted a cross-sectional, stratified cluster, random sample study to measure the seroprevalence of antibodies to dengue virus (DENV) in Mexico. The target population was school children ages 6-17 y from 22 endemic states in Mexico, clustered in four regions: Pacific, South-Central, Southeast and Low. Results: A total of 2134 subjects provided blood samples for immunoglobulin G antibody detection in serum by enzyme-linked immunosorbent assay. Overall, the seroprevalence of antibodies against DENV was 33.5% (95% confidence interval [CI] 27.5 to 40.1). The Southeast had the highest regional seroprevalence, reaching 70.9% (95% CI 60.3 to 79.7). Seroprevalence was higher in older children in the Southeast region: 62.1% (95% CI 46.9 to 75.2) in children 6-8 y and 82.6% (95% CI 73.8 to 88.9) in 13-17 years old (y). However, this was not consistent in all regions. Seroprevalence was associated with dengue incidence. Conclusions: DENV seroprevalence in Mexico was found to be heterogeneous at the country, regional and state levels. Seroprevalence was linked to long-term exposure and did not adequately reflect recent patterns of transmission, suggesting that utilization of a single epidemiological indicator to define endemic regions should be avoided.

Dengue virus infection induces chromatin remodeling at locus AAEL006536 in the midgut of Aedes aegypti.

OBJECTIVE: To identify and characterize Aedes aegypti's AAEL006536 gene proximal upstream cis-regulatory sequences activated by dengue virus infection. MATERIALS AND METHODS: A. aegypti Rockefeller strain mosquitoes were blood fed or infected with dengue virus 2. Open chromatinprofiling was then carried out in pools of midguts from each group of mosquitoes. RESULTS: The proximal upstream region does not contain open chromatin sites in the midguts of blood-fed mosquitoes as detected by FAIRE-qPCR. In contrast, two cis-regulatory sites were identified in the same upstream region of dengue virus-infected mosquito midguts. The distal sequence contains STAT-, REL- and C/EBP-type transcription factor binding sites. CONCLUSIONS: The activation of two proximal cis-regulatory sequences, induced by dengue virus infection, is mediated by chromatin remodeling mechanisms. Binding sites suggest a dengue virus infectioninduced participation of immunity transcription factors in the up-regulation of this gene. This suggests the participation of the AAEL006536 gene in the mosquito's antiviral innate immune response.

Dengue virus infection induces chromatin remodeling at locus AAEL006536 in the midgut of Aedes aegypti / La infección por virus dengue induce remodelación de la cromatina en el locus AAEL006536 en el intestino medio de Aedes aegypti

Abstract: Objective: To identify and characterize Aedes aegypti's AAEL006536 gene proximal upstream cis-regulatory sequences activated by dengue virus infection. Materials and methods: A. aegypti Rockefeller strain mosquitoes were blood fed or infected with dengue virus 2. Open chromatin profiling was then carried out in pools of midguts from each group of mosquitoes. Results: The proximal upstream region does not contain open chromatin sites in the midguts of blood-fed mosquitoes as detected by FAIRE-qPCR. In contrast, two cis-regulatory sites were identified in the same upstream region of dengue virus-infected mosquito midguts. The distal sequence contains STAT-, REL- and C/EBP-type transcription factor binding sites. Conclusion: The activation of two proximal cis-regulatory sequences, induced by dengue virus infection, is mediated by chromatin remodeling mechanisms. Binding sites suggest a dengue virus infection-induced participation of immunity transcription factors in the up-regulation of this gene. This suggests the participation of the AAEL006536 gene in the mosquito's antiviral innate immune response.

Resumen: Objetivo: Identificar y caracterizar las secuencias reguladoras activadas por la infección por virus dengue en la región proximal del gen AAEL006536 de Aedes aegypti. Material y métodos: Mosquitos de la cepa Rockefeller de A. aegypti se infectaron con virus dengue o se alimentaron con sangre. Se obtuvieron los perfiles de cromatina abierta del locus en los intestinos de cada uno de los grupos. Resultados: Se identificaron dos sitios reguladores solo en los intestinos de mosquitos infectados por virus dengue. El sitio distal contiene sitios de unión a factores de transcripción tipo REL, STAT y C/EBP. Conclusiones: La activación de dos sitios reguladores proximales está mediada por la remodelación de la cromatina. Los sitios de unión a factores de transcripción en el sitio regulador distal sugieren la participación de las vías de inmunidad en la regulación del gen. Esto sugiere la participación de este gen en la respuesta inmune del mosquito frente a la infección viral.

Participation of dengue virus NS4B protein in the modulation of immune effectors dependent on ER stress in insect cells.

Organisms' reactions to adverse events result in the generation of immune effectors, which, in the case of insects, may be produced from the direct activation of pathways such as Toll, Jak-STAT, Imd, or RNAi or may be derived from the crosstalk of different intracellular pathways. One such pathway, the unfolded protein response (UPR), has the primary objective of restoring homeostasis in the endoplasmic reticulum. In addition, the UPR participates in signaling crosstalk with the immune pathways, generating protection against pathogenic organisms. Dengue virus is a plus-strand RNA virus belonging to the Flavivirus genus that uses the ER as a replication site; during the infection, there are indicators of the activation of the UPR, which in turn, induces the synthesis of internal membranes and preferential translation of viral proteins enhancing the replication. One of the dengue virus proteins, the NS4B can block the pathway of α/ß interferon in mammals. However, what happen in insects is interesting because the lack of the main antiviral pathway, the interferon and the role of the NS4B protein in the UPR-immunity relationship can be better understood. Thus, in this study, we demonstrated that the DENV2/16681 NS4B protein is capable of modulating the immune effectors that result from the activation of the UPR in insect cells.

ADE and dengue vaccination.

The vaccine against Dengue virus (DENV), Dengvaxia® (CYD), produced by Sanofi-Pasteur, has been registered by several national regulatory agencies; nevertheless, the performance and security of this vaccine have been challenged in a series of recent papers. In this work, we intend to contribute to the debate by analyzing the concept of an enhancing vaccine, presenting objections to the epidemiological model base of the concept and, likewise, presenting data that contradict that concept.

Analysis of spatial mobility in subjects from a Dengue endemic urban locality in Morelos State, Mexico.

INTRODUCTION: Mathematical models and field data suggest that human mobility is an important driver for Dengue virus transmission. Nonetheless little is known on this matter due the lack of instruments for precise mobility quantification and study design difficulties. MATERIALS AND METHODS: We carried out a cohort-nested, case-control study with 126 individuals (42 cases, 42 intradomestic controls and 42 population controls) with the goal of describing human mobility patterns of recently Dengue virus-infected subjects, and comparing them with those of non-infected subjects living in an urban endemic locality. Mobility was quantified using a GPS-data logger registering waypoints at 60-second intervals for a minimum of 15 natural days. RESULTS: Although absolute displacement was highly biased towards the intradomestic and peridomestic areas, occasional displacements exceeding a 100-Km radius from the center of the studied locality were recorded for all three study groups and individual displacements were recorded traveling across six states from central Mexico. Additionally, cases had a larger number of visits out of the municipality´s administrative limits when compared to intradomestic controls (cases: 10.4 versus intradomestic controls: 2.9, p = 0.0282). We were able to identify extradomestic places within and out of the locality that were independently visited by apparently non-related infected subjects, consistent with houses, working and leisure places. CONCLUSIONS: Results of this study show that human mobility in a small urban setting exceeded that considered by local health authority's administrative limits, and was different between recently infected and non-infected subjects living in the same household. These observations provide important insights about the role that human mobility may have in Dengue virus transmission and persistence across endemic geographic areas that need to be taken into account when planning preventive and control measures. Finally, these results are a valuable reference when setting the parameters for future mathematical modeling studies.

Dengue in Latin America: Systematic Review of Molecular Epidemiological Trends.

Dengue, the predominant arthropod-borne viral disease affecting humans, is caused by one of four distinct serotypes (DENV-1, -2, -3 or -4). A literature analysis and review was undertaken to describe the molecular epidemiological trends in dengue disease and the knowledge generated in specific molecular topics in Latin America, including the Caribbean islands, from 2000 to 2013 in the context of regional trends in order to identify gaps in molecular epidemiological knowledge and future research needs. Searches of literature published between 1 January 2000 and 30 November 2013 were conducted using specific search strategies for each electronic database that was reviewed. A total of 396 relevant citations were identified, 57 of which fulfilled the inclusion criteria. All four dengue virus serotypes were present and co-circulated in many countries over the review period (with the predominance of individual serotypes varying by country and year). The number of countries in which more than one serotype circulated steadily increased during the period under review. Molecular epidemiology data were found for Argentina, Bolivia, Brazil, the Caribbean region, Colombia, Ecuador, Mexico and Central America, Paraguay, Peru and Venezuela. Distinct lineages with different dynamics were found in each country, with co-existence, extinction and replacement of lineages occurring over the review period. Despite some gaps in the literature limiting the possibility for comparison, our review has described the molecular epidemiological trends of dengue infection. However, several gaps in molecular epidemiological information across Latin America and the Caribbean were identified that provide avenues for future research; in particular, sequence determination of the dengue virus genome is important for more precise phylogenetic classification and correlation with clinical outcome and disease severity.

A prospective cohort study to assess seroprevalence, incidence, knowledge, attitudes and practices, willingness to pay for vaccine and related risk factors in dengue in a high incidence setting.

BACKGROUND: Dengue is one of the most important vector-borne diseases in the world, causing significant morbidity and economic impact. In Colombia, dengue is a major public health problem. Departments of La Guajira, Cesar and Magdalena are dengue endemic areas. The objective of this research is to determine the seroprevalence and the incidence of dengue virus infection in the participating municipalities from these Departments, and also establish the association between individual and housing factors and vector indices with seroprevalence and incidence. We will also assess knowledge, attitudes and practices, and willingness-to-pay for dengue vaccine. METHODS: A cohort study will be assembled with a clustered multistage sampling in 11 endemic municipalities. Approximately 1000 homes will be visited to enroll people older than one year who living in these areas, who will be followed for 1 year. Dengue virus infections will be evaluated using IgG indirect ELISA and IgM and IgG capture ELISA. Additionally, vector indices will be measured, and adult mosquitoes will be captured with aspirators. Ovitraps will be used for continuous estimation of vector density. DISCUSSION: This research will generate necessary knowledge to design and implement strategies with a multidimensional approach that reduce dengue morbidity and mortality in La Guajira and other departments from Colombian Caribbean.