Dengue virus (DENV) is a global health threat, with approximately 390 million infections annually, ranging from mild dengue fever to severe dengue hemorrhagic fever and shock syndrome. MicroRNA (miRNA) are crucial post-transcriptional regulators which may regulate host resistance to DENV infection. This study aimed to identify miRNAs involved in natural resistance to DENV infection. Individuals from a dengue-endemic area were classified as susceptible (SD) or resistant (RD) according to their anti-DENV antibody status. RD individuals were seronegative despite high local DENV infection prevalence. Monocytes susceptibility to DENV infection was assessed in vitro. The miRNome profiles of the monocytes from 7 individuals per group were assessed upon mock or DENV-2 infection. The antiviral effect of differentially expressed miRNAs was analyzed using miRNA mimics in HeLa cells followed by infection with DENV-1, DENV-2, DENV-3, and DENV-4 serotypes. We performed RNA-seq on miRNA mimic-transfected cells to identify miRNA-targeted genes interacting with DENV proteins. Monocytes from RD individuals exhibit lower DENV-2 production in vitro. The miRNAs miR-155, miR-132-3p, miR-576-5p were overexpressed in monocytes from RD group upon DENV-2 infection. The transfection of miR-155-5p mimic reduced DENV infection and viral production in HeLa cells, regulating 18 genes interacting with DENV proteins and downregulating target genes involved in interferon response, TP53 regulation, apoptosis, and vesicle trafficking (e.g. HSD17B12, ANXA2). Therefore, we show that monocytes from RD individuals show a distinct miRNA expression profile and reduced viral production. In vitro miR-155-5p upregulation induces an antiviral state, revealing potential therapeutic targets to treat dengue.

Sickle cell trait is the quintessential example of the human evolutionary response to malaria, providing protection against severe disease, but leading to sickle cell disease (SCD) in the homozygous state. Fetal Hemoglobin (HbF) reduces the pathology of SCD and several mutations lead to the prolonged production of HbF into childhood and adult life. HbF has been suggested to contribute to protection against malaria. Two long-term cohorts were genotyped for three quantitative trait loci associated with HbF production and analyzed for HbF titers, malaria clinical episodes and the production of parasite stages infectious to mosquitoes, gametocytes, in asymptomatic infections. Plasmodium falciparum parasites were also grown in vitro in HbSS cells with measured levels of HbF. The genetic determinants of prolonged HbF production were associated with increased HbF titers and that increased HbF afforded protection from malaria disease but increased the production of gametocytes. The presence of HbF in sickled red cells was also shown in in vitro culture to enable parasite persistence in conditions otherwise deleterious for the parasite and enabled complete maturation of gametocytes. The beneficial personal effect of HbF, whether through protection against malaria or alleviating effects of SCD, is seemingly offset by increased parasite transmissibility and potential disease burden for the community. These individuals represent a potentially important reservoir of infection and could be targeted in elimination strategies.

BackgroundDengue is an increasing health burden that has spread throughout the tropics and sub-tropics. There is currently no effective vaccine and control is only possible through integrated vector management. Early warning systems (EWS) to alert potential dengue outbreaks are currently being explored but despite showing promise are yet to come to fruition. This study addresses the association of meteorological variables with both mosquito indices and dengue incidences and assesses the added value of additionally using mosquito indices for predicting dengue incidences.Methodology/Principal findingsEntomological surveys were carried out monthly for 14 months in six sites spread across three environmentally different cities of the Philippines. Meteorological and dengue data were acquired. Non-linear generalized additive models were fitted to test associations of the meteorological variables with both mosquito indices and dengue cases. Rain and the diurnal temperature range (DTR) contributed most to explaining the variation in both mosquito indices and number of dengue cases. DTR and minimum temperature also explained variation in dengue cases occurring one and two months later and may offer potentially useful variables for an EWS. The number of adult mosquitoes did associate with the number of dengue cases, but contributed no additional value to meteorological variables for explaining variation in dengue cases.Conclusions/SignificanceThe use of meteorological variables to predict future risk of dengue holds promise. The lack of added value of using mosquito indices confirms several previous studies and given the onerous nature of obtaining such information, more effort should be placed on improving meteorological information at a finer scale to evaluate efficacy in early warning of dengue outbreaks.

Ticks are known vectors of various pathogens, including bacteria, parasites and viruses, that impact both animal and human health. Improving knowledge of the distribution of tick-borne pathogens, combined with their early detection in ticks, are essential steps to fight against tick-borne diseases and mitigate their impacts. Here we give an overview of what are the common methods of pathogen detection in tick samples, including recent developments concerning how to handle tick samples, get access to tick-borne pathogens by chemical or physical disruption of the ticks, and methods used for the RNA/DNA extraction steps. Furthermore, we discuss promising tools that are developed for other sample types such as serum or blood to detect tick-borne pathogens, and those that could be used in the future for tick samples.

The transmissibility of SARS-CoV-2 is anticipated to increase in the winter because of increased viral survival in cold damp air and thus would exacerbate viral spread in community. Analysis to capture the seasonal trend is needed to be prepared for future epidemics. We compared regression models for the 5-week case prior to each epidemic peak week for both the COVID-19 and influenza epidemics in winter and summer. The weekly case increase ratio was compared, using non-paired t tests between seasons. In order to test the robustness of seasonal transmission patterns, the normalized weekly case numbers of COVID-19 and influenza case rates of all seasons were assessed in a combined quadratic regression analysis. In winter, the weekly case increase ratio accelerated before epidemic peaks, similarly, for both COVID-19 and influenza. The quadratic regression models of weekly cases were observed to be convex curves in the winter and concave curves in the spring/summer for both COVID-19 and influenza. A significant increase of case increase ratio (3.19 [95%CI:0.01-6.37, P = .049]) of the COVID-19 and influenza epidemics was observed in winter as compared to spring/summer before the epidemic peak. The epidemic of COVID-19 was found to mirror that of influenza, suggesting a strong underlying seasonal transmissibility. Influenza epidemics can potentially be a useful reference for the COVID-19 epidemics.(c) 2022 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Our study assessed the impact of using ovitraps with pyriproxyfen on mosquito populations and the feasibility of using human saliva samples to test for seroconversion to dengue virus (DENV). We used a quasi-experimental research design by forming the intervention (n = 220) and the control (n = 223) groups in neighboring Taguig City, Philippines, over 4 months. Socio-demographic data, entomological indices, and IgG antibodies against DENV were measured. Associations between the implementation of ovitraps dosed with pyriproxyfen and mosquito densities (percentage positive ovitraps and container indices) and DENV seroconversion were calculated post-intervention in Months 2, 3, and 4. Among the participants recruited at baseline, 17 and 13 were seropositive for dengue (DENV) in the intervention and control groups, respectively. Both entomological indices were lower in the treated area than the control site at post-intervention Months 2, 3, and 4, but not earlier. Dengue seroconversions rates decreased in the treated population, but not significantly so. In conclusion, the use of PPF-treated ovitraps may have impacted the mosquito population, but not seroconversion rates. Compliance in providing saliva samples and the ability to detect IgG antibodies within these samples was encouraging and suggests that further studies on larger populations for longer durations are warranted.

There was an error in the original article [...].

ResuméCombined with sanitation and social distancing measures, control of human mobility has quickly been targeted as a major leverage to contain the spread of SARS-CoV-2 in a great majority of countries worldwide. The extent to which such measures were successful, however, is uncertain (Gibbs et al. 2020; Kraemer et al. 2020). Very few studies are quantifying the relation between mobility, lockdown strategies and the diffusion of the virus in different countries. Using the anonymised data collected by one of the major social media platforms (Facebook) combined with spatial and temporal Covid-19 data, the objective of this research is to understand how mobility patterns and SARS-CoV-2 diffusion during the first wave are connected in four different countries: the west coast of the USA, Colombia, Sweden and France. Our analyses suggest a relatively modest impact of lockdown on the spread of the virus at the national scale. Despite a varying impact of lockdown on mobility reduction in these countries (83% in France and Colombia, 55% in USA, 10% in Sweden), no country successfully implemented control measures to stem the spread of the virus. As observed in Hubei (Chinazzi et al. 2020), it is likely that the virus had already spread very widely prior to lockdown; the number of affected administrative units in all countries was already very high at the time of lockdown despite the low testing levels. The second conclusion is that the integration of mobility data considerably improved the epidemiological model (as revealed by the QAIC). If inter-individual contact is a fundamental element in the study of the spread of infectious diseases, it is also the case at the level of administrative units. However, this relational dimension is little understood beyond the individual scale mostly due to the lack of mobility data at this scale. Fortunately, these types of data are getting increasingly provided by social media or mobile operators, and they can be used to help administrations to observe changes in movement patterns and/or to better locate where to implement disease control measures such as vaccination (Pollina & Busvine 2020; Pullano et al. 2020; Romm et al. 2020).

Significance Human T cell leukemia virus type 1 (HTLV-1) proviral load is associated with the risk of developing HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP) and several small-scale candidate gene approaches have also identified associations of particular HLA alleles with HAM/TSP risk. However, no large-scale genome-wide association (GWA) studies have been performed to date. By a large-scale GWA study and comprehensive genotyping of classical HLA genes, we found that HLA-DRB1 alleles carrying leucine at the antigen presentation groove domain (DRB1-GB-7-Leu) increased the susceptibility to HAM/TSP. Individuals who were homozygous for DRB1-GB-7-Leu had a ninefold increased odds of developing HAM/TSP. This effect of DRB1-GB-7-Leu was independent of proviral load. These findings identify DRB1-GB-7-Leu as a genetic risk marker of HAM/TSP development.

Our study assessed the impact of using ovitraps with pyriproxyfen on mosquito populations and the feasibility of using human saliva samples to test for seroconversion to dengue virus (DENV). We used a quasi-experimental research design by forming the intervention (n=220) and the control (n=223) groups in neighboring Taguig City, Philippines, over four months. Socio-demographic data, entomological indices, and IgG antibodies against DENV were measured. Associations between the implementation of ovitraps dosed with pyriproxyfen and mosquito densities (percentage positive ovitraps and container indices) and DENV seroconversion were calculated post-intervention in Months 2, 3, and 4. Among participants recruited at baseline, 17 and 13 were seropositive for dengue (DENV) in the intervention and control groups, respectively. Both entomological indices were lower in the treated area than the control site at months two, three, and four post-interventions but not earlier. Dengue seroconversions rates did decrease in the treated population but not significantly so. In conclusion, the use of PPF-treated ovitraps impacted the mosquito population but not the seroconversion rates. Compliance to provide saliva samples and the ability to detect IgG antibodies within these samples were encouraging and suggested that further studies on a larger population and longer duration are warranted.

Aedes aegypti is the main vector of dengue globally. The variables that influence the abundance of dengue vectors are numerous and complex. This has generated a need to focus on areas at risk of disease transmission, the spatial-temporal distribution of vectors, and the factors that modulate vector abundance. To help guide and improve vector-control efforts, this study identified the ecological, social, and other environmental risk factors that affect the abundance of adult female and immature Ae. aegypti in households in urban and rural areas of northeastern Thailand. A one-year entomological study was conducted in four villages of northeastern Thailand between January and December 2019. Socio-demographic; self-reported prior dengue infections; housing conditions; durable asset ownership; water management; characteristics of water containers; knowledge, attitudes, and practices (KAP) regarding climate change and dengue; and climate data were collected. Household crowding index (HCI), premise condition index (PCI), socio-economic status (SES), and entomological indices (HI, CI, BI, and PI) were calculated. Negative binomial generalized linear models (GLMs) were fitted to identify the risk factors associated with the abundance of adult females and immature Ae. aegypti. Urban sites had higher entomological indices and numbers of adult Ae. aegypti mosquitoes than rural sites. Overall, participants’ KAP about climate change and dengue were low in both settings. The fitted GLM showed that a higher abundance of adult female Ae. aegypti was significantly (p < 0.05) associated with many factors, such as a low education level of household respondents, crowded households, poor premise conditions, surrounding house density, bathrooms located indoors, unscreened windows, high numbers of wet containers, a lack of adult control, prior dengue infections, poor climate change adaptation, dengue, and vector-related practices. Many of the above were also significantly associated with a high abundance of immature mosquito stages. The GLM model also showed that maximum and mean temperature with four-and one-to-two weeks of lag were significant predictors (p < 0.05) of the abundance of adult and immature mosquitoes, respectively, in northeastern Thailand. The low KAP regarding climate change and dengue highlights the engagement needs for vector-borne disease prevention in this region. The identified risk factors are important for the critical first step toward developing routine Aedes surveillance and reliable early warning systems for effective dengue and other mosquito-borne disease prevention and control strategies at the household and community levels in this region and similar settings elsewhere.

Global urbanization is leading to an inexorable spread of several major diseases that need to be stemmed. Dengue is one of these major diseases spreading in cities today, with its principal mosquito vector superbly adapted to the urban environment. Current mosquito control strategies are proving inadequate, especially in the face of such urbanisation and novel, evidence-based targeted approaches are needed. Through combined epidemiological and entomological approaches, we aimed to identify a novel sanitation strategy to alleviate the burden of dengue through how the dengue virus spreads through the community. We combined surveillance case mapping, prospective serological studies, year-round mosquito surveys, socio-economic and Knowledge Attitudes and Practices surveys across Delhi. We identified lack of access to tap water (≤98%) as an important risk factor for dengue virus IgG sero-positivity (adjusted Odds Ratio 4.69, 95% C.I. 2.06–10.67) and not poverty per se . Wealthier districts had a higher dengue burden despite lower mosquito densities than the Intermediary income communities (adjusted Odds Ratio 2.92, 95% C.I. 1.26–6.72). This probably reflects dengue being introduced by people travelling from poorer areas to work in wealthier houses. These poorer, high density areas, where temperatures are also warmer, also had dengue cases during the winter. Control strategies based on improved access to a reliable supply of tap water plus focal intervention in intra-urban heat islands prior to the dengue season could not only lead to a reduction in mosquito abundance but also eliminate the reservoir of dengue virus clearly circulating at low levels in winter in socio-economically disadvantaged areas.

Dengue is the most rapidly spreading mosquito-borne viral disease in the world. The detection of clinical cases enables us to measure the incidence of dengue infection, whereas serological surveys give insights into the prevalence of infection. This study aimed to determine dengue seroprevalence and seroconversion rates in northeastern Thailand and southern Laos and to assess any association of mosquito control methods and socioeconomic factors with dengue virus (DENV) infection. Cross-sectional seroprevalence surveys were performed in May and November 2019 on the same individuals. Blood samples were collected from one adult and one child, when possible, in each of 720 randomly selected households from two urban and two rural sites in both northeastern Thailand and southern Laos. IgG antibodies against DENV were detected in serum using a commercial enzyme-linked immunosorbent assay (ELISA) kit. Overall, 1071 individuals participated in the study. The seroprevalence rate was high (91.5%) across all 8 study sites. Only age and province were associated with seroprevalence rates. There were 33 seroconversions during the period from May to November, of which seven reported fever. More than half of the seroconversions occurred in the rural areas and in Laos. Dengue seroconversion was significantly associated with young age (<15 years old), female gender, province, and duration of living in the current residence. No socioeconomic factors or mosquito control methods were found to be associated with seroprevalence or seroconversion. Notably, however, the province with most seroconversions had lower diurnal temperature ranges than elsewhere. In conclusion, our study has highlighted the homogeneity of dengue exposure across a wide range of settings and most notably those from rural and urban areas. Dengue can no longer be considered to be solely an urban disease nor necessarily one linked to poverty.

The global burden of dengue is increasing at an alarming rate and increased international travel will lead to constant importation of dengue virus into non-endemic areas. The potential for dengue epidemics in such countries during seasons with permissive temperatures has already been underlined by epidemics in Japan and Madeira. While improved surveillance can help identify clinical cases of dengue, differentiating between imported and autochthonous cases remains problematical. Implementation of a threshold criterion can help in identifying aberrant incidences of dengue. This threshold approach was applied to dengue cases reported in the Japanese surveillance system from 2011–2019. Several aberrant incidences occurring during consecutive weeks were detected, one of which was concomitant to the Yoyogi Park Tokyo epidemic but in another area, Kanagawa, and another above threshold week was coincidental with a symptomatic case of a German traveller. This indicates autochthonous transmission. Despite the occurrence of several alert periods, however, on no occasion did the spread of dengue progress into a full epidemic as was seen in Yoyogi. It thus seems likely that Yoyogi Park was a particular event and that stochastic die-out of viruses is occurring frequently without progression, perhaps reflecting the negative impact of societal infra-structure on dengue transmission despite permissive temperatures. Implementation of a dengue epidemic threshold as used for seasonal influenza may provide a basis for future seroprevalence studies to assess the true prevalence of dengue in light of the high frequency of subclinical, asymptomatic infections.

Dengue is a continuous health burden in Laos and Thailand. We assessed and mapped dengue vulnerability in selected provinces of Laos and Thailand using multi-criteria decision approaches. An ecohealth framework was used to develop dengue vulnerability indices (DVIs) that explain links between population, social and physical environments, and health to identify exposure, susceptibility, and adaptive capacity indicators. Three DVIs were constructed using two objective approaches, Shannon’s Entropy (SE) and the Water-Associated Disease Index (WADI), and one subjective approach, the Best-Worst Method (BWM). Each DVI was validated by correlating the index score with dengue incidence for each spatial unit (district and subdistrict) over time. A Pearson’s correlation coefficient (r) larger than 0.5 and a p-value less than 0.05 implied a good spatial and temporal performance. Spatially, DVIWADI was significantly correlated on average in 19% (4–40%) of districts in Laos (mean r = 0.5) and 27% (15–53%) of subdistricts in Thailand (mean r = 0.85). The DVISE was validated in 22% (12–40%) of districts in Laos and in 13% (3–38%) of subdistricts in Thailand. The DVIBWM was only developed for Laos because of lack of data in Thailand and was significantly associated with dengue incidence on average in 14% (0–28%) of Lao districts. The DVIWADI indicated high vulnerability in urban centers and in areas with plantations and forests. In 2019, high DVIWADI values were observed in sparsely populated areas due to elevated exposure, possibly from changes in climate and land cover, including urbanization, plantations, and dam construction. Of the three indices, DVIWADI was the most suitable vulnerability index for the study area. The DVIWADI can also be applied to other water-associated diseases, such as Zika and chikungunya, to highlight priority areas for further investigation and as a tool for prevention and interventions.

Cities worldwide are facing ever-increasing pressure to develop mitigation strategies for all sectors to deal with the impacts of climate change. Cities are expected to house 70% of the world's population by 2050, and developing related resilient health systems is a significant challenge. Because of their physical nature, cities' surface temperatures are often substantially higher than that of the surrounding rural areas, generating the so-called Urban Heat Island (UHI) effect. Whilst considerable emphasis has been placed on strategies to mitigate against the UHI-associated negative health effects of heat and pollution in cities, mosquito-borne diseases have largely been ignored. However, the World Health Organization estimates that one of the main consequences of global warming will be an increased burden of mosquito-borne diseases, many of which have an urban facet to their epidemiology and thus the global population exposed to these pathogens will steadily increase. Current health mitigation strategies for heat and pollution, for example, may, however, be detrimental for mosquito-borne diseases. Implementation of multi-sectoral strategies that can benefit many sectors (such as water, labor, and health) do exist or can be envisaged and would enable optimal use of the meagre resources available. Discussion among multi-sectoral stakeholders should be actively encouraged.

Background: Dengue infection is a global health threat. While symptomatic cases contribute to morbidity and mortality, the majority of infected people are asymptomatic but serve as an important reservoir. However, the kinetics of viremia in asymptomatic infections remains unknown. Methods: We enrolled 279 hospital-based symptomatic index cases and quantified dengue virus (DENV) RNA at enrollment and at the day of defervescence. To identify asymptomatic cases, 175 household members of index cases were monitored for clinical symptoms during follow-up, and blood was taken twice weekly to test for and quantify DENV RNA until cleared. Results: We detected DENV in thirteen asymptomatic household members (7.43%). Their DENV serotypes were primarily the same as those of their family index cases. The median peak DENV viremia in asymptomatic subjects was lower than that of symptomatic individuals during the febrile phase, and the viral decay rate was slower in asymptomatic infections. Conclusions: DENV level and kinetics in asymptomatic individuals differed significantly from those of symptomatic cases. Despite the lower viremia, the slower decay rate in asymptomatic infections could lead to their prolonging the infectious reservoir. The improvement of transmission control to prevent such long-lived asymptomatic infections from transmitting the DENV is needed.

Understanding the transition of epidemic to endemic dengue transmission remains a challenge in regions where serotypes co-circulate and there is extensive human mobility. French Polynesia, an isolated group of 117 islands of which 72 are inhabited, distributed among five geographically separated subdivisions, has recorded mono-serotype epidemics since 1944, with long inter-epidemic periods of circulation. Laboratory confirmed cases have been recorded since 1978, enabling exploration of dengue epidemiology under monotypic conditions in an isolated, spatially structured geographical location. A database was constructed of confirmed dengue cases, geolocated to island for a 35-year period. Statistical analyses of viral establishment, persistence and fade-out as well as synchrony among subdivisions were performed. Seven monotypic and one heterotypic dengue epidemic occurred, followed by low-level viral circulation with a recrudescent epidemic occurring on one occasion. Incidence was asynchronous among the subdivisions. Complete viral die-out occurred on several occasions with invasion of a new serotype. Competitive serotype replacement has been observed previously and seems to be characteristic of the South Pacific. Island population size had a strong impact on the establishment, persistence and fade-out of dengue cases and endemicity was estimated achievable only at a population size in excess of 175 000. Despite island remoteness and low population size, dengue cases were observed somewhere in French Polynesia almost constantly, in part due to the spatial structuration generating asynchrony among subdivisions. Long-term persistence of dengue virus in this group of island populations may be enabled by island hopping, although could equally be explained by a reservoir of sub-clinical infections on the most populated island, Tahiti.

L’etude du lien entre la mobilite des Hommes et des virus est une problematique recurrente de l’epidemiologie, des sciences humaines de la sante et plus largement de la sante publique. A la faveur de la pandemie de Covid-19 et des mesures de confinement prises par les etats, celle-ci emerge de maniere spectaculaire dans la sphere publique. Pour autant, si de nombreuses recherches scientifiques traitent du lien entre mobilites et diffusion des virus a l’echelle internationale, plusieurs – minoritaires – mettent en avant la necessite d’integrer a l’analyse les mobilites nationales et regionales. Jusqu’a present, ces donnees de mobilite etaient aux mieux parcellaires, agregees spatialement et limitees dans le temps, lorsqu’elles existaient. Quand la diffusion des virus s’opere avant tout a une echelle fine, cette lacune ne favorisait pas la resilience des territoires faisant face a une circulation croissante des virus emergents.