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Non-polio enteroviruses in faeces of children diagnosed with acute flaccid paralysis in Nigeria.

BackgroundThe need to investigate the contribution of non-polio enteroviruses to acute flaccid paralysis (AFP) cannot be over emphasized as we move towards a poliovirus free world. Hence, we aim to identify non-polio enteroviruses recovered from the faeces of children diagnosed with AFP in Nigeria.\n\nMethodsNinety-six isolates, (95 unidentified and one previously confirmed Sabin poliovirus 3) recovered on RD cell culture from the stool of children <15 years old diagnosed with AFP in 2014 were analyzed. All isolates were subjected to RNA extraction, cDNA synthesis and three different PCR reactions (one panenterovirus 5'-UTR and two VP1 amplification assays). VP1 amplicons were then sequenced isolates identified.\n\nResults93.75% (90/96) of the isolates were detected by at least one of the three assays as an enterovirus. Precisely, 79.17% (76/96), 6.25% (6/96), 7.295% (7/96) and 6.25% (6/96) of the isolates were positive for both, positive and negative, negative and positive, as well as negative for both the 5'-UTR and VP1 assays, respectively. In this study, sixty-nine (69) of the 83 VP1 amplicons sequenced were identified as 27 different enterovirus types. The most commonly detected were CV-B3 (10 isolates) and EV-B75 (5 isolates). Specifically, one, twenty-four and two of the enterovirus types identified in this study belong to EV-A, EV-B and EV-C respectively.\n\nDiscussionThis study reports the circulating strains of 27 non-polio enterovirus types in Nigerian children with AFP in 2014 and Nigerian strains of CV-B2, CV-B4, E17, EV-B80, EV-B73, EV-B97, EV-B93, EV-C99 and EV-A120.

epidemiology

Enterovirus A119 in a child with Acute Flaccid Paralysis, Nigeria

The oldest EV-A119 record was in 2008 in a chimpanzee in Cameroon and subsequently in more non-human primates and healthy children. Here we report for the first time the detection of EV-A119 in a child with Acute Flaccid Paralysis, thus suggesting possible association with a clinical condition in humans.

epidemiology

Can you catch Ebola from a stork bite? Inductive reasoning influences on zoonosis risk perception

Emerging zoonoses are a prominent global health threat. Human beliefs are central to drivers of emerging zoonoses, yet little is known about the factors that influence perceived risks of animal contact. We present an inductive account of zoonosis risk perception, suggesting that beliefs about the range of animals that are able to transmit diseases to each other influence zoonosis risk perception. Consistent with our account, in Study 1, we find that participants who endorse higher likelihoods of cross-species disease transmission have stronger intention to report animal bites. In Study 2, using real world descriptions of Ebola virus from the WHO and CDC, we find that communications conveying a broader range of animals as susceptible increase intentions to report animal bites and decrease perceived safety of wild game meat. These results suggest that cognitive factors may be harnessed to modulate zoonosis risk perception and combat emerging infectious diseases.

epidemiology

The Utility of Red Cell Distribution Width as a Parameter for Calculating Indices of Allostatic Load

BackgroundAllostatic Load is a construct used to quantify the cumulative burden of exposure to stressors that, over the course of an individuals life, exert a toll on the bodys physiological functions, increasing risks of various chronic ailments and conditions. Studies attempting to quantify allostatic load have used a variety of clinical biomarkers representing primary and secondary mediators. In this study, we demonstrate the value of including red blood cell distribution width (RDW) among the panel of clinical parameters used to calculate allostatic load.\n\nMethodsWe develop a novel formulation of allostatic load using RDW and other standard biomarkers. This index is computed using clinical laboratory data from the NHANES study. The predictive validity of the new index for tertiary outcomes (all-cause mortality and physician-assessed health status) is compared to that of the current formulation using Harrells C index, ROC analysis and regression-based goodness-of-fit measures.\n\nResultsInclusion of RDW as an allostatic load biomarker yields a significantly improved index. It demonstrates a superior ability to predict mortality, health status and biological age than the standard formulation currently in use.\n\nConclusionRDW has shown strong correlations with mortality and a broad spectrum of diseases. A review of the existing literature on allostatic load reveals its underutilization in this area, despite being a standard component of blood count panels. This study is the first to demonstrate its usefulness as a potential allostatic load biomarker.

epidemiology

Exposure to Wood Smoke is Associated with Increased Risk of Asthma and Respiratory Symptoms in a Honduran Population

BackgroundExposure to environmental pollutants has been shown to be associated with asthma, but few studies have evaluated the effect of wood smoke on asthma and disease severity in a developing country, where use of stoves powered by solid fuels is a common practice.\n\nObjectiveIn a population in Olancho, Honduras, we evaluated the association between cooking fuel, stove type and asthma. We also evaluated the effects of these factors on asthma symptoms, lung function, and atopy.\n\nMethodsParticipants with physician-diagnosed asthma (n = 597) and controls without asthma (n = 429) were recruited from the Olancho province in Honduras. Participants were interviewed using a questionnaire and their baseline pulmonary function was measured using spirometry.\n\nResultsThe prevalence of use of wood as a cooking fuel was 66.9% in the study population, of which 42.1% of participants used wood as their only fuel. Use of wood as a cooking fuel was more prevalent among households with lower income, lower maternal education, and less urbanization. The prevalence of use of an open wood stove as the primary cooking stove among participants with asthma was 6.2% higher (95% CI 0.8 - 11.7%, p = .02) than among healthy controls. In a multiple logistic regression model, we identified a significant association between use of an open wood stove and asthma (OR = 1.80, 95% CI = 1.17 - 2.78, p = 0.007), compared to the referent (electric) stove category. Among participants with asthma, we identified a significant association between use of wood as cooking fuel and increased daytime respiratory symptoms (OR = 1.46, CI: 1.01 - 2.58, p = 0.046) and nocturnal symptoms (OR = 2.51, CI: 1.04 - 2.62, p = 0.04), though not with pulmonary function. Among control participants without asthma, use of wood as cooking fuel was associated with atopy (OR = 1.94, CI = 1.14 - 3.33, p = 0.015) and cough (OR = 2.22, CI = 1.09 - 4.88, p = 0.04).\n\nConclusionsUse of an open wood stove for cooking in a developing country appears to be a significant risk factor for asthma and respiratory symptoms. Exposure to wood smoke may play a role in atopic sensitization and respiratory symptoms, leading to the development of obstructive lung disease in susceptible individuals.

epidemiology

The origin and evolution of a pandemic lineage of the kiwifruit pathogen Pseudomonas syringae pv. actinidiae

Recurring epidemics of kiwifruit (Actinidia spp.) bleeding canker disease are caused by Pseudomonas syringae pv. actinidiae (Psa), whose emergence coincided with domestication of its host. The most recent pandemic has had a deleterious effect on kiwifruit production worldwide. In order to strengthen understanding of population structure, phylogeography and evolutionary dynamics of Psa, we sampled 746 Pseudomonas isolates from cultivated and wild kiwifruit across six provinces in China, of which 87 were Psa. Of 234 Pseudomonas isolated from wild Actinidia spp. none were identified as Psa. Genome sequencing of fifty isolates and the inclusion of an additional thirty from previous studies show that China is the origin of the recently emerged pandemic lineage. However China harbours only a fraction of global Psa diversity, with greatest diversity found in Korea and Japan. Distinct transmission events were responsible for introduction of the pandemic lineage of Psa into New Zealand, Chile and Europe. Two independent transmission events occurred between China and Korea, and two Japanese isolates from 2014 cluster with New Zealand Psa. Despite high similarity at the level of the core genome and negligible impact of within-lineage recombination, there has been substantial gene gain and loss even within the single clade from which the global pandemic arose.\n\nSIGNIFICANCE STATEMENTBleeding canker disease of kiwifruit caused by Pseudomonas syringae pv. actinidiae (Psa) has come to prominence in the last three decades. Emergence has coincided with domestication of the host plant and provides a rare opportunity to understand ecological and genetic factors affecting the evolutionary origins of Psa. Here, based on genomic analysis of an extensive set of strains sampled from China and augmented by isolates from a global sample, we show, contrary to earlier predictions, that China is not the native home of the pathogen, but is nonetheless the source of the recent global pandemic. Our data identify specific transmission events, substantial genetic diversity and point to non-agricultural plants in either Japan or Korea as home to the source population.

epidemiology

Mathematical models of SIR disease spread with combined non-sexual and sexual transmission routes

The emergence of diseases such as Zika and Ebola has highlighted the need to understand the role of sexual transmission in the spread of diseases with a primarily non-sexual transmission route. In this paper we develop a number of low-dimensional models which are appropriate for a range of assumptions for how a disease will spread if it has sexual transmission through a sexual contact network combined with some other transmission mechanism, such as direct contact or vectors. The equations derived provide exact predictions for the dynamics of the corresponding simulations in the large population limit.

epidemiology

Modeling disease spread in populations with birth, death, and concurrency

The existence of sexual partnerships that overlap in time (concurrent relationships) is believed by some to be a significant contributing factor to the spread of HIV, although this is controversial. We derive an analytic model which allows us to investigate and compare disease spread in populations with and without concurrency. We can identify regions of parameter space in which its impact is negligible, and other regions in which it plays a major role. We also see that the impact of concurrency on the initial growth phase can be much larger than its impact on the equilibrium size. We see that the effect of concurrency saturates, which leads to the perhaps surprising conclusion that interventions targeting concurrency may be most effective in populations with low to moderate levels of concurrency.\n\nAuthor SummaryWe consider the spread of an infectious disease through a population modeled by a dynamic network with demographic turnover. We develop a stochastic model of the disease and derive governing equations that exactly predict the large population (deterministic) limit of the stochastic model. We use this to investigate the role of concurrency and find that interventions targeting concurrency may be most effective in populations with lower levels of concurrency.\n\nOur model is not intended to be an accurate representation of any single population. Rather it is intended to give general insights for intervention design and to provide a framework which can be further specialized to particular populations.\n\nThis model is the first model to allow for analytic investigation of the impact of concurrent partnerships in a population exhibiting demographic turnover. Thus it will be useful for investigating the \"concurrency hypothesis.\"

epidemiology

A location-specific spreadsheet for estimating Zika risk and timing for Zika vector surveillance, using U.S. military facilities as an example

Local Zika virus transmission in the United States involving one or both of the known vector species, Aedes aegypti and Ae. albopictus, is of major concern. To assist efforts to anticipate the risks of transmission, we developed an Excel spreadsheet tool that uses vector and virus temperature thresholds, remotely sensed maximum temperature, and habitat suitability from models to answer the questions: \"is Zika transmission likely here?\" and \"when should we conduct vector surveillance?\". An example spreadsheet, updated regularly and freely available, uses near real-time and forecast temperature data to generate guidance, based on a novel four level Zika risk code, for 733 U.S. military facilities in the 50 states, the District of Columbia, and the territories of Guam and Puerto Rico.

epidemiology

Structure of general-population antibody titer distributions to influenza A virus

Seroepidemiological studies aim to understand population-level exposure and immunity to infectious diseases. Results from serological assays are normally presented as binary outcomes describing the presence or absence of pathogen-specific antibody, despite the fact that many assays measure continuous quantities. A populations natural distribution of antibody titers to an endemic infectious disease may in fact include information on multiple serological states - e.g. naivete, recent infection, non-recent infection - depending on the disease in question and the acquisition and waning patterns of host immunity. In this study, we investigate a collection of 20,152 general-population serum samples from southern Vietnam collected between 2009 and 2013 from which we report antibody titers to the influenza virus HA1 protein using a continuous titer measurement from a protein microarray assay. We describe the distributions of antibody titers to subtypes 2009 H1N1 and H3N2. Using a model selection approach to fit mixture distributions, we show that 2009 H1N1 antibody titers fall into four titer subgroups and that H3N2 titers fall into three subgroups. For H1N1, our interpretation is that the two highest-titer subgroups correspond to recent infection and historical infection, which is consistent with 2009 pandemic attack rates. For H3N2, observations censored at the highest titer dilutions make similar interpretations difficult to validate.

epidemiology

The risk of sustained sexual transmission of Zika is underestimated

Pathogens can follow more than one transmission route during outbreaks - from needle sharing plus sexual transmission of HIV to small droplet aerosol plus fomite transmission of influenza. Thus, controlling an infectious disease outbreak often requires characterizing the risk associated with multiple mechanisms of transmission. For example, during the Ebola virus outbreak in West Africa, weighing the relative importance of funeral versus health care worker transmission was essential to stopping disease spread [1]. Strategic policy decisions regarding interventions must rely on accurately characterizing risks associated with multiple transmission routes. The ongoing Zika virus outbreak challenges our conventional methodologies for translating case-counts into route-specific transmission risk. Critically, most approaches will fail to accurately estimate the risk of seeing sustained sexual transmission of a pathogen that is primarily vectored by a mosquito - ...

epidemiology

Cannabis use and risk of schizophrenia:a Mendelian randomization study

Cannabis use is observationally associated with an increased risk of schizophrenia, however whether the relationship is causal is not known. To determine the nature of the association between cannabis use on risk of schizophrenia using Mendelian randomization (MR) analysis, we used ten genetic variants previously identified to associate with cannabis use in 32,330 individuals. Genetic variants were used in a MR analyses of the association of genetically determined cannabis on risk of schizophrenia in 34,241 cases and 45,604 controls from predominantly European descent. Estimates from MR were compared to a metaanalysis of observational studies reporting effect estimates for ever use of cannabis and risk of schizophrenia or related disorders. Genetically determined use of cannabis was associated with increased risk of schizophrenia (OR of schizophrenia for users vs. non-users of cannabis: 1.37; 95%CI, 1.09 to 1.67; P-value=0.007). The corresponding estimate from observational analysis was 1.50 (95% CI, 1.10 to 2.00; P-value for heterogeneity = 0.88). The genetic instrument did not show evidence of pleiotropy on MR-Egger (Egger test, P-value=0.292) nor on multivariable MR accounting for tobacco exposure (OR of schizophrenia for users vs. nonusers of cannabis, adjusted for ever vs. never smoker: 1.41; 95% CI, 1.09-1.83). Furthermore, the causal estimate remained robust to sensitivity analyses. These findings strongly support a causal association between genetically determined use of cannabis and risk of schizophrenia. Such robust evidence may inform public health message about the risks of cannabis use, especially regarding its potential mental health consequences.

epidemiology

Detecting telomere elongation in longitudinal datasets: Analysis of a proposal by Simons, Stulp and Nakagawa

Telomere shortening has emerged as an important biomarker of aging. Longitudinal studies consistently find that, although telomere length shortens over time on average, there is a subset of individuals for whom telomere length is observed to increase. This apparent lengthening could either be a genuine biological phenomenon, or simply due to measurement and sampling error. Simons, Stulp and Nakagawa [Biogerontology 15: 99-103, 2014] recently proposed a statistical test for detecting when the amount of apparent lengthening in a dataset exceeds that which should be expected due to error, and thus indicating that genuine elongation may be operative in some individuals. The test is however based on a restrictive assumption, namely that each individuals true rate of telomere change is constant over time. It is not currently known whether this assumption is true. Here we show, using simulated datasets, that with perfect measurement and large sample size, the test has high power to detect true lengthening as long as the true rate of shortening is either constant, or moderately stable, over time. If the true rate of lengthening varies randomly from year to year, the test systematically returns type-II errors. We also consider the impact of measurement error. Using estimates of the magnitude of annual attrition and of measurement error derived from the human telomere literature, we show that power of the test is likely to be low in several empirically-realistic scenarios, even in large samples. Thus, whilst a significant result of the proposed test is likely to indicate that true lengthening is present in a data set, type-II errors are a likely outcome, either if measurement error is substantial, and/or the true rate of attrition varies substantially over time within individuals.

epidemiology

The Impact of Vitamin A and Carotenoids on the Risk of Tuberculosis Progression

BackgroundLow and deficient levels of vitamin A are common in low and middle income countries where tuberculosis burden is high. We assessed the impact of baseline levels of vitamins A and carotenoids on TB disease risk.\n\nMethods and FindingsWe conducted a case-control study nested within a longitudinal cohort of household contacts of pulmonary TB cases in Lima, Peru. We screened all contacts for TB disease at 2, 6, and 12 months after enrollment. We defined cases as HIV-negative household contacts with blood samples who developed TB disease at least 15 days after enrollment of the index patient. For each case, we randomly selected 4 controls from among contacts who did not develop TB disease, matching on gender and year of age. We used conditional logistic regression to estimate odds ratios (ORs) for incident TB disease by vitamin A and carotenoids levels, controlling for other nutritional and socioeconomic factors.\n\nAmong 6751 HIV-negative household contacts with baseline blood samples, 192 developed secondary TB disease during follow-up. We analyzed 180 cases with viable samples and 709 matched controls. After controlling for possible confounders, we found that baseline vitamin A deficiency was associated with a 10-fold increase in risk of TB disease among household contacts (aOR 10.42; 95% CI 4.01-27.05; p < 0.001). This association was dose-dependent with stepwise increases in TB disease risk with each decreasing quartile of vitamin A level. Carotenoid levels were also inversely associated with TB risk among adolescents.\n\nOur study is limited by the one year duration of follow up and by the relatively few blood samples available from household contacts under ten years of age.\n\nConclusionsVitamin A deficiency strongly predicted risk of incident TB disease among household contacts of TB patients. Vitamin A supplementation among individuals at high risk of TB may provide an effective means of preventing TB disease.

epidemiology

Surveillance to Establish Elimination of Transmission and Freedom from Dog-mediated Rabies

BackgroundWith a global target set for zero human deaths from dog-mediated rabies by 2030 and some regional programmes close to eliminating canine rabies, there is an urgent need for enhanced surveillance strategies suitable for declaring freedom from disease and elimination of transmission with known confidence.\n\nMethodsUsing exhaustive contact tracing across settings in Tanzania we generated detailed data on rabies incidence, rabid dog biting behaviour and health-seeking behaviour of bite victims. Using these data we compared case detection of sampling-based and enhanced surveillance methodologies and investigated elimination verification procedures.\n\nFindingsWe demonstrate that patients presenting to clinics with bite injuries are sensitive sentinels for identifying dog rabies cases. Triage of patients based on bite history criteria and investigation of suspicious incidents can confirm >10% of dog rabies cases and is an affordable approach that will enable validation of disease freedom following two years without case detection. Approaches based on sampling the dog population without using bite-injury follow-up were found to be neither sensitive nor cost-effective.\n\nInterpretationThe low prevalence of rabies, and short window in which disease can be detected, preclude sampling-based surveillance. Instead, active case finding guided by bite-patient triage is needed as elimination is approached. Our proposed methodology is affordable, practical and supports the goal of eliminating human rabies deaths by improving administration of lifesaving post-exposure prophylaxis for genuinely exposed but untreated contacts. Moreover, joint investigations by public health and veterinary workers will strengthen intersectoral partnerships and capacity for control of emerging zoonoses.

epidemiology

Modeling HIV disease progression and transmission at population-level: The potential impact of modifying disease progression in HIV treatment programs

IntroductionMathematical models of HIV transmission that incorporate the dynamics of disease progression can estimate the potential impact of adjunctive strategies to antiretroviral therapy (ART) for HIV treatment and prevention. Suppressive treatment of HIV-positive persons co-infected with herpes simplex virus-2 (HSV-2) with valacyclovir, a medication directed against HSV-2, can lower HIV viral load, but the impact of valacyclovir on population HIV transmission has not been estimated.\n\nMethodsWe applied data on CD4 and viral load progression in ART-naive persons studied in two HIV clinical trials to a novel, discrete-time Markov model. We validated our disease progression estimates using data from a trial of home-based HIV counseling and testing in KwaZulu-Natal, South Africa. Finally, we applied our disease progression estimates to a dynamic transmission model estimating the impact of providing valacyclovir to ART-naive individuals to reduce onward transmission of HIV in three scenarios of different ART and valacyclovir population coverage. We assumed that valacyclovir reduced HIV viral load by 1.23 log copies/L, and that persons treated with valacyclovir initiated ART more rapidly when their CD4 fell below 500 due to improved retention in pre-ART care.\n\nResultsThe average duration of HIV infection following acute infection was 9.5 years. The duration of disease after acute infection and before reaching CD4 200 cells/L was 2.53 years longer for females than males. Relative to a baseline of community HIV testing and counseling and ART initiation at CD4 <=500 cells/L, valacyclovir with increased linkage to care resulted in 166,000 fewer HIV infections over ten years, with an incremental cost-effectiveness ratio (ICER) of $4,696 per HIV infection averted. The Test and Treat scenario with 70% ART coverage and no valacyclovir resulted in 202,000 fewer HIV infections at an ICER of $6,579.\n\nConclusionEven when compared with initiation of valacyclovir, a safe drug that reduces HIV viral load, universal treatment for HIV is the optimal strategy for averting new infections and increasing public health benefit. Universal HIV treatment should be pursued by all countries to most effectively and efficiently reduce the HIV burden.

epidemiology

Association between urinary biomarkers of total sugars and sucrose intake and BMI in a cross-sectional study

Obesity is an important modifiable risk factors for chronic diseases. While there is increasing focus on the role of dietary sugars, there remains a paucity of data establishing the association between sugar intake and obesity in the general public. The objective of this study was to investigate associations of estimated sugar intake with odds for obesity in a representative samples of English adults. We used data from 434 participants of the 2005 Health Survey of England. Biomarkers for total sugar intake were measured in 24h urine samples and used to estimate intake. Linear and logistic regression analyses were used to investigate associations between estimated intake and measures of obesity (BMI, waist circumference and waist-to-hip ratio) and obesity risk., respectively. Estimated sugars intake was significantly associated with BMI, waist circumference and waist-to-hip ratio, and these associations remained significant after adjustment for estimated protein intake. Estimated sugars intake was also associated with increased odds for obesity based on BMI (OR 1.02; 95% CI 1.00; 1.04 per 10 g), waist-circumference (OR 1.03; 95% CI 1.01; 1.05) and waist-to-hip ratio (OR 1.04; 95% CI 1.02; 1.06); all OR estimates remained significant after adjusting for estimated protein intake. Our results show a significant association between biomarker-estimated total sugars intake and both measures of obesity and obesity risk, confirming positive associations between total sugar intake, measures of obesity and obesity risk. This biomarker could be used to monitor the efficacy of public health interventions.

epidemiology

Spatial point pattern analysis of prehospital naloxone administrations

ObjectivesThe increasing problem in the United States with opioid dependence and overdose, often fatal, is well-recognized. As naloxone has only one clinical use--the treatment of opioid overdose--its administration by EMS personnel can serve as a surveillance indicator for opioid overdose. This study uses specific locations of EMS calls, and methods of point pattern analysis, to detect overall spatial clustering among EMS naloxone administrations compared to EMS calls in general.\n\nStudy DesignA cross-sectional study of incident locations of EMS responses in a three-county EMS region in the United States.\n\nMethodsRepeated random samples from the spatial distribution of all EMS calls were used, in a Monte Carlo simulation, to represent the background inhomogeneity of the population. Observed F, G, and inhomogeneous K and L functions from the spatial distribution of naloxone-involved calls were compared to their null sampling distributions obtained from the Monte Carlo simulation.\n\nResultsCases of naloxone administration demonstrated spatial clustering in the range of 0 to 5000 meters, and particularly around 2500 meters, beyond what could be attributable to the spatial heterogeneity of all EMS calls.\n\nConclusionsEfforts to understand the fundamental nature of opioid overdose as a spatial point process could yield innovative public health interventions to control the epidemic.

epidemiology