Host outdoor exposure variability affects the transmission and spread of Zika virus: Insights for epidemic control.
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ABSTRACT: Zika virus transmission dynamics in urban environments follow a complex spatiotemporal pattern that appears unpredictable and barely related to high mosquito density areas. In this context, human activity patterns likely have a major role in Zika transmission dynamics. This paper examines the effect of host variability in the amount of time spent outdoors on Zika epidemiology in an urban environment.First, we performed a survey on time spent outdoors by residents of Miami-Dade County, Florida. Second, we analyzed both the survey and previously published national data on outdoors time in the U.S. to provide estimates of the distribution of the time spent outdoors. Third, we performed a computational modeling evaluation of Zika transmission dynamics, based on the time spent outdoors by each person. Our analysis reveals a strong heterogeneity of the host population in terms of time spent outdoors-data are well captured by skewed gamma distributions. Our model-based evaluation shows that in a heterogeneous population, Zika would cause a lower number of infections than in a more homogenous host population (up to 4-fold differences), but, at the same time, the epidemic would spread much faster. We estimated that in highly heterogeneous host populations the timing of the implementation of vector control measures is the major factor for limiting the number of Zika infections.Our findings highlight the need of considering host variability in exposure time for managing mosquito-borne infections and call for the revision of the triggers for vector control strategies, which should integrate mosquito density data and human outdoor activity patterns in specific areas.
<h4>Background</h4>Zika virus transmission dynamics in urban environments follow a complex spatiotemporal pattern that appears unpredictable and barely related to high mosquito density areas. In this context, human activity patterns likely have a major role in Zika transmission dynamics. This paper examines the effect of host variability in the amount of time spent outdoors on Zika epidemiology in an urban environment.<h4>Methodology/principal findings</h4>First, we performed a survey on time sp ...[more]
Project description:The epidemic of Zika virus (ZIKV) infection in South America has led to World Health Organization's declaration of a Public Health Emergency of International Concern. To further inform effective public health policy, an understanding of ZIKV's transmission mechanisms is crucial. To characterize the intercontinental transmission of ZIKV, we compiled and analyzed more than 250 gene sequences together with their sequence-related geographic and temporal information, sampled across 27 countries spanning from 1947 to 2016. After filtering and selecting appropriate sequences, extensive phylogenetic analyses were performed. Although phylogeographic reconstruction supported the transmission route of the virus in Africa, South-eastern Asia, Oceania and Latin America, we discovered that the Eastern Africa origin of ZIKV was disputable. On a molecular level, purifying selection was found to be largely responsible for the evolution of non-structural protein 5 and envelope protein E. Our dataset and ancestral sequences reconstruction analysis captured previously unidentified amino acid changes during evolution. Finally, based on the estimation of the time to the most recent common ancestors for the non-structural protein 5 gene, we hypothesized potential specific historic events that occurred in the 1940s and might have facilitated the spread of Zika virus from Africa to South-eastern Asia. Our findings provide new insights into the transmission characteristics of ZIKV, while further genetic and serologic studies are warranted to support the design of tailored prevention strategies.
Project description:The factors that enhance the transmission of pathogens during epidemic spread are ill defined. Water-borne spread of the diarrhoeal disease cholera occurs rapidly in nature, whereas infection of human volunteers with bacteria grown in vitro is difficult in the absence of stomach acid buffering. It is unclear, however, whether stomach acidity is a principal factor contributing to epidemic spread. Here we report that characterization of Vibrio cholerae from human stools supports a model whereby human colonization creates a hyperinfectious bacterial state that is maintained after dissemination and that may contribute to epidemic spread of cholera. Transcriptional profiling of V. cholerae from stool samples revealed a unique physiological and behavioural state characterized by high expression levels of genes required for nutrient acquisition and motility, and low expression levels of genes required for bacterial chemotaxis.
Project description:BackgroundZika virus (ZIKV) emerged as a global epidemic in 2015-2016 from Latin America with its true geographical extent remaining unclear due to widely presumed underreporting. The identification of locations with potential and unknown spread of ZIKV is a key yet understudied component for outbreak preparedness. Here, we aim to identify locations at a high risk of cryptic ZIKV spread during 2015-2016 to further the understanding of the global ZIKV epidemiology, which is critical for the mitigation of the risk of future epidemics.MethodsWe developed an importation simulation model to estimate the weekly number of ZIKV infections imported in each susceptible spatial unit (i.e. location that did not report any autochthonous Zika cases during 2015-2016), integrating epidemiological, demographic, and travel data as model inputs. Thereafter, a global risk model was applied to estimate the weekly ZIKV transmissibility during 2015-2016 for each location. Finally, we assessed the risk of onward ZIKV spread following importation in each susceptible spatial unit to identify locations with a high potential for cryptic ZIKV spread during 2015-2016.ResultsWe have found 24 susceptible spatial units that were likely to have experienced cryptic ZIKV spread during 2015-2016, of which 10 continue to have a high risk estimate within a highly conservative scenario, namely, Luanda in Angola, Banten in Indonesia, Maharashtra in India, Lagos in Nigeria, Taiwan and Guangdong in China, Dakar in Senegal, Maputo in Mozambique, Kinshasa in Congo DRC, and Pool in Congo. Notably, among the 24 susceptible spatial units identified, some have reported their first ZIKV outbreaks since 2017, thus adding to the credibility of our results (derived using 2015-2016 data only).ConclusionOur study has provided valuable insights into the potentially high-risk locations for cryptic ZIKV circulation during the 2015-2016 pandemic and has also laid a foundation for future studies that attempt to further narrow this key knowledge gap. Our modelling framework can be adapted to identify areas with likely unknown spread of other emerging vector-borne diseases, which has important implications for public health readiness especially in resource-limited settings.
Project description:The epidemic spread of infectious diseases is ubiquitous and often has a considerable impact on public health and economic wealth. The large variability in the spatio-temporal patterns of epidemics prohibits simple interventions and requires a detailed analysis of each epidemic with respect to its infectious agent and the corresponding routes of transmission. To facilitate this analysis, we introduce a mathematical framework which links epidemic patterns to the topology and dynamics of the underlying transmission network. The evolution, both in disease prevalence and transmission network topology, is derived from a closed set of partial differential equations for infections without allowing for recovery. The predictions are in excellent agreement with complementarily conducted agent-based simulations. The capacity of this new method is demonstrated in several case studies on HIV epidemics in synthetic populations: it allows us to monitor the evolution of contact behavior among healthy and infected individuals and the contributions of different disease stages to the spreading of the epidemic. This gives both direction to and a test bed for targeted intervention strategies for epidemic control. In conclusion, this mathematical framework provides a capable toolbox for the analysis of epidemics from first principles. This allows for fast, in silico modeling--and manipulation--of epidemics and is especially powerful if complemented with adequate empirical data for parameterization.
Project description:Disease epidemics typically begin as an outbreak of a relatively small, spatially explicit population of infected individuals (focus), in which disease prevalence increases and rapidly spreads into the uninfected, at-risk population. Studies of epidemic spread typically address factors influencing disease spread through the at-risk population, but the initial outbreak may strongly influence spread of the subsequent epidemic.We initiated wheat stripe rust Puccinia striiformis f. sp. tritici epidemics to assess the influence of the focus on final disease prevalence when the degree of disease susceptibility differed between the at-risk and focus populations.When the focus/at-risk plantings consisted of partially genetic resistant and susceptible cultivars, final disease prevalence was statistically indistinguishable from epidemics produced by the focus cultivar in monoculture. In these experimental epidemics, disease prevalence was not influenced by the transition into an at-risk population that differed in disease susceptibility. Instead, the focus appeared to exert a dominant influence on the subsequent epidemic.Final disease prevalence was not consistently attributable to either the focus or the at-risk population when focus/at-risk populations were planted in a factorial set-up with a mixture (~28% susceptible and 72% resistant) and susceptible individuals. In these experimental epidemics, spatial heterogeneity in disease susceptibility within the at-risk population appeared to counter the dominant influence of the focus.Cessation of spore production from the focus (through fungicide/glyphosate application) after 1.3 generations of stripe rust spread did not reduce final disease prevalence, indicating that the focus influence on disease spread is established early in the epidemic.Synthesis and applications. Our experiments indicated that outbreak conditions can be highly influential on epidemic spread, even when disease resistance in the at-risk population is greater than that of the focus. Disease control treatments administered shortly after the initial outbreak within the focus may either prevent an epidemic from occurring or reduce its severity.
Project description:BackgroundLyme disease is the most common reportable zoonotic infection in the United States. Recent data suggest spread of the Ixodes tick vector and increasing incidence of Lyme disease in several states, including Pennsylvania. We sought to determine the clinical presentation and healthcare use patterns for pediatric Lyme disease in western Pennsylvania.MethodsThe electronic medical records of all patients with an International Classification of Disease, Ninth Revision, diagnosis of Lyme disease between 2003 and 2013 at Children's Hospital of Pittsburgh were individually reviewed to identify confirmed cases of Lyme disease. The records of 773 patients meeting these criteria were retrospectively analyzed for patient demographics, disease manifestations, and healthcare use.ResultsAn Lyme disease increased exponentially in the pediatric population of western Pennsylvania. There was a southwestward migration of Lyme disease cases, with a shift from rural to nonrural zip codes. Healthcare provider involvement evolved from subspecialists to primary care pediatricians and emergency departments (EDs). Patients from nonrural zip codes more commonly presented to the ED, while patients from rural zip codes used primary care pediatricians and EDs equally.ConclusionsThe current study details the conversion of western Pennsylvania from a Lyme-naive to a Lyme-epidemic area, highlighting changes in clinical presentation and healthcare use over time. Presenting symptoms and provider type differed between those from rural and nonrural zip codes. By elucidating the temporospatial epidemiology and healthcare use for pediatric Lyme disease, the current study may inform public health measures regionally while serving as an archetype for other areas at-risk for Lyme disease epidemics.
Project description:Timely, accurate, and comparative data on human mobility is of paramount importance for epidemic preparedness and response, but generally not available or easily accessible. Mobile phone metadata, typically in the form of Call Detail Records (CDRs), represents a powerful source of information on human movements at an unprecedented scale. In this work, we investigate the potential benefits of harnessing aggregated CDR-derived mobility to predict the 2015-2016 Zika virus (ZIKV) outbreak in Colombia, when compared to other traditional data sources. To simulate the spread of ZIKV at sub-national level in Colombia, we employ a stochastic metapopulation epidemic model for vector-borne diseases. Our model integrates detailed data on the key drivers of ZIKV spread, including the spatial heterogeneity of the mosquito abundance, and the exposure of the population to the virus due to environmental and socio-economic factors. Given the same modelling settings (i.e. initial conditions and epidemiological parameters), we perform in-silico simulations for each mobility network and assess their ability in reproducing the local outbreak as reported by the official surveillance data. We assess the performance of our epidemic modelling approach in capturing the ZIKV outbreak both nationally and sub-nationally. Our model estimates are strongly correlated with the surveillance data at the country level (Pearson's r = 0.92 for the CDR-informed network). Moreover, we found strong performance of the model estimates generated by the CDR-informed mobility networks in reproducing the local outbreak observed at the sub-national level. Compared to the CDR-informed networks, the performance of the other mobility networks is either comparatively similar or substantially lower, with no added value in predicting the local epidemic. This suggests that mobile phone data captures a better picture of human mobility patterns. This work contributes to the ongoing discussion on the value of aggregated mobility estimates from CDRs data that, with appropriate data protection and privacy safeguards, can be used for social impact applications and humanitarian action.
Project description:Zika Virus (ZIKV) is a flavivirus that is transmitted predominantly by the Aedes species of mosquito, but also through sexual contact, blood transfusions, and congenitally from mother to child. Although approximately 80% of ZIKV infections are asymptomatic and typical symptoms are mild, multiple studies have demonstrated a causal link between ZIKV and severe diseases such as Microcephaly and Guillain Barré Syndrome. Two goals of this study are to improve ZIKV models by considering the spread dynamics of ZIKV as both a vector-borne and sexually transmitted disease, and also to approximate the degree of under-reporting. In order to accomplish these objectives, we propose a compartmental model that allows for the analysis of spread dynamics as both a vector-borne and sexually transmitted disease, and fit it to the ZIKV incidence reported to the National System of Public Health Surveillance in 27 municipalities of Colombia between January 1 2015 and December 31 2017. We demonstrate that our model can represent the infection patterns over this time period with high confidence. In addition, we argue that the degree of under-reporting is also well estimated. Using the model we assess potential viability of public health scenarios for mitigating disease spread and find that targeting the sexual pathway alone has negligible impact on overall spread, but if the proportion of risky sexual behavior increases then it may become important. Targeting mosquitoes remains the best approach of those considered. These results may be useful for public health organizations and governments to construct and implement suitable health policies and reduce the impact of the Zika outbreaks.
Project description:The recent Zika virus (ZIKV) outbreak in the Americas surprised all of us because of its rapid spread and association with neurologic disorders including fetal microcephaly, brain and ocular anomalies, and Guillain?Barré syndrome. In response to this global health crisis, unprecedented and world-wide efforts are taking place to study the ZIKV-related human diseases. Much has been learned about this virus in the areas of epidemiology, genetic diversity, protein structures, and clinical manifestations, such as consequences of ZIKV infection on fetal brain development. However, progress on understanding the molecular mechanism underlying ZIKV-associated neurologic disorders remains elusive. To date, we still lack a good understanding of; (1) what virologic factors are involved in the ZIKV-associated human diseases; (2) which ZIKV protein(s) contributes to the enhanced viral pathogenicity; and (3) how do the newly adapted and pandemic ZIKV strains alter their interactions with the host cells leading to neurologic defects? The goal of this review is to explore the molecular insights into the ZIKV?host interactions with an emphasis on host cell receptor usage for viral entry, cell innate immunity to ZIKV, and the ability of ZIKV to subvert antiviral responses and to cause cytopathic effects. We hope this literature review will inspire additional molecular studies focusing on ZIKV?host Interactions.
Project description:The Liverpool epidemic strain (LES) is an important transmissible clonal lineage of Pseudomonas aeruginosa that chronically infects the lungs of people with cystic fibrosis (CF). Previous studies have focused on the genomics of the LES in a limited number of isolates, mostly from one CF centre in the UK, and from studies highlighting identification of the LES in Canada. Here we significantly extend the current LES genome database by genome sequencing 91 isolates from multiple CF centres across the UK, and we describe the comparative genomics of this large collection of LES isolates from the UK and Canada. Phylogenetic analysis revealed that the 145 LES genomes analysed formed a distinct clonal lineage when compared with the wider P. aeruginosa population. Notably, the isolates formed two clades: one associated with isolates from Canada, and the other associated with UK isolates. Further analysis of the UK LES isolates revealed clustering by clinic geography. Where isolates clustered closely together, the association was often supported by clinical data linking isolates or patients. When compared with the earliest known isolate, LESB58 (from 1988), many UK LES isolates shared common loss-of-function mutations, such as in genes gltR and fleR. Other loss-of-function mutations identified in previous studies as common adaptations during CF chronic lung infections were also identified in multiple LES isolates. Analysis of the LES accessory genome (including genomic islands and prophages) revealed variations in the carriage of large genomic regions, with some evidence for shared genomic island/prophage complement according to clinic location. Our study reveals divergence and adaptation during the spread of the LES, within the UK and between continents.
