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Almost all cases of human listeriosis are foodborne, however the proportion where specific exposures are identified is small. Between 1981 and 2015, 5252 human listeriosis cases were reported in England and Wales. The purpose of this study was to summarise data where consumption of specific foods was identified with transmission and these comprised 11 sporadic cases and 17 outbreaks. There was a single outbreak in the community of 378 cases (7% of the total) which was associated with pâté consumption and 112 cases (2% of the total) attributed to specific foods in all the other incidents. The proportion of food-attributed cases increased during this study with improvements in typing methods for Listeria monocytogenes. Ten incidents (one sporadic case and nine outbreaks of 2–9 cases over 4 days to 32 months) occurred in hospitals: all were associated with the consumption of pre-prepared sandwiches. The 18 community incidents comprised eight outbreaks (seven of between 3 and 17 cases) and 10 sporadic cases: food of animal origin was implicated in 16 of the incidents (sliced or potted meats, pork pies, pâté, liver, chicken, crab-meat, butter and soft cheese) and food of non-animal origin in the remaining two (olives and vegetable rennet).
The aim of this study was to evaluate long-term survival and risk factors associated with multidrug-resistant tuberculosis (MDR-TB) patient survival in Central China. Between December 2006 and June 2011, incident and retreatment adult MDR-TB patients were enrolled in the present study. Cox proportional hazard regression analysis was used to evaluate the risk factors affecting survival. The total follow-up period was 270 person-years (PY) for 356 MDR-TB cases in Wuhan. Of the 356 cases, 103 patients died, yielding an average case fatality rate of 381.2 per 1000 TB patients per year. Using adjusted Cox regression analysis, older age (adjusted hazard ratio (aHR) >3.0 starting from 30 years) and low education level (primary and middle school; aHR 1.67 (95% CI 1.01–2.77)) were independently associated with lower survival. Diabetes mellitus profoundly affected the survival of MDR-TB patients (aHR 1.95 (95% CI 1.30–2.93)). Our data demonstrate that coexistent diabetes significantly and negatively impacted MDR-TB patient survival. In addition, MDR-TB patients aged 60 years or older exhibited a greater risk of mortality during follow-up. Our findings emphasise that MDR-TB patients with comorbidities that increase their risk of death require additional medical interventions to reduce mortality.
Cytomegalovirus (CMV) enters latency after primary infection and can reactivate periodically with virus excreted in body fluids which can be called shedding. CMV shedding during the early stage of pregnancy is associated with adverse pregnancy outcome. The shedding pattern in healthy seropositive women who plan to have babies has not been well characterised. Vaginal swabs, urine and blood were collected from 1262 CMV IgG-positive women who intended to have babies and tested for CMV DNA by fluorogenic quantitative PCR method. Serum IgM was also detected. The association between sociodemographic characteristics and CMV shedding prevalence was analysed. Among 1262 seropositive women, 12.8% (161/1262) were detected CMV DNA positive in at least one body fluid. CMV DNA was more frequently detected in vaginal secretion (10.5%) than in urine (3.2%) and blood (0.6%) also with higher viral loads (P < 0.00). CMV shedding was more likely detected in IgM-positive women than IgM-negative women (29.5% (13/44) vs. 12.2% (148/1218); OR 3.03, 95% CI 1.55–5.93; P = 0.001). CMV shedding in vaginal secretion was highly correlated with shedding in urine, the immune state of IgM, the adverse pregnant history and younger age. CMV shedding was more commonly detected in vaginal secretion than in urine or blood with higher viral loads among healthy seropositive women of reproductive age. Further studies are needed to figure out whether the shedding is occasional or continuous and whether it is associated with adverse pregnancy outcomes.
Accurate methods for determining the duration of HIV infection at the individual level are valuable in many settings, including many critical research studies and in clinical practice (especially for acute infection). Since first published in 2003, the ‘Fiebig staging system’ has been used as the primary way of classifying early HIV infection into five sequential stages based on HIV test result patterns in newly diagnosed individuals. However, Fiebig stages can only be assigned to individuals who produce both a negative and a positive test result on the same day, on specific pairs of tests of varying ‘sensitivity’. Further, in the past 16 years HIV-testing technology has evolved substantially, and three of the five key assays used to define Fiebig stages are no longer widely used. To address these limitations, we developed an improved and more general framework for estimating the duration of HIV infection by interpreting any combination of diagnostic test results, whether obtained on single or multiple days, into an estimated date of detectable infection, or EDDI. A key advantage of the EDDI method over Fiebig staging is that it allows for the generation of a point estimate, as well as an associated credibility interval for the date of first detectable infection, for any person who has at least one positive and one negative HIV test of any kind. The tests do not have to be run on the same day; they do not have to be run during the acute phase of infection and the method does not rely on any special pairing of tests to define ‘stages’ of infection. The size of the interval surrounding the EDDI (and therefore the precision of the estimate itself) depends largely on the length of time between negative and positive tests. The EDDI approach is also flexible, seamlessly incorporating any assay for which there is a reasonable diagnostic delay estimate. An open-source, free online tool includes a user-updatable curated database of published diagnostic delays. HIV diagnostics have evolved tremendously since that original publication more than 15 years ago, and it is time to similarly evolve the methods used to estimate timing of infection. The EDDI method is a flexible and rigorous way to estimate the timing of HIV infection in a continuously evolving diagnostic landscape.
Despite a sizeable evidence base for the risk of campylobacteriosis associated with eating chicken liver pâté, associated outbreaks continue to occur. In January 2017, six cases of campylobacteriosis reported having eaten a Christmas set-menu meal at the same hotel in North Yorkshire, England on the same day. A retrospective cohort study was undertaken to test the null hypothesis that consumption of individual food items was not associated with an increased risk of illness. There were 19 cases of campylobacteriosis linked to the outbreak; seven confirmed and 12 probable cases. Chicken liver pâté was the food item most strongly associated with illness (P < 0.001) with a corresponding high crude relative risk (12.95). This relationship was supported by multivariable analysis, sensitivity analyses and a clear dose–response relationship. Three cases reported an incubation period of <24 h, consistent with other outbreaks of campylobacteriosis associated with consumption of poultry liver. The findings were suggestive of a single point source exposure with a strong association between the consumption of chicken liver pâté and campylobacteriosis. This outbreak highlights that despite evidence that simple cooking techniques can ensure that all campylobacter are killed during cooking, outbreaks continue to occur. Public and professional awareness needs to be raised through a strategic communication plan to reduce the risk of further outbreaks of campylobacteriosis linked to incorrectly cooked chicken liver dishes.
In the event of a Legionnaires' disease outbreak, rapid location and control of the source of bacteria are crucial for outbreak management and regulation. In this paper, we describe an enhancement of the traditional wind rose for epidemiological use; shifting the focus of measurement from relative frequency of the winds speeds and directions to the relative volume of air carried, whilst also incorporating probability distributions of disease incubation periods to refine identification of the important wind directions during a cases window of exposure, i.e. from which direction contaminated aerosols most likely originated. The probability-weighted wind rose offers a potential improvement over the traditional wind rose by weighting the importance of wind measurements through incorporation of probability of exposure given an individual's time of symptom onset (obtained through knowledge of the incubation period), and by instead focusing on the volume of carrying air which offers better insight into the most probable direction of the source. This then provides a probabilistic distribution of which direction the wind was blowing around the time of infection. We discuss how the probability-weighted wind rose can be implemented during a Legionnaires' disease outbreak, and how outbreak control teams might use it as supportive evidence to identify the most likely direction of the contaminated source from the presumed site of exposure. In addition, this paper discusses how minor adjustments can be made to the method allowing the probability-weighted wind rose to be applied to other non-communicable airborne diseases, providing the disease's probability distribution for the incubation period distribution is well known.
Chikungunya virus (CHIKV) is a re-emerging pathogen of global importance. We attempted to gain an insight into the organisation, distribution and mutational load of the virus strains reported from different parts of the world. We describe transmission dynamics and genetic characterisation of CHIKV across the globe during the last 65 years from 1952 to 2017. The evolutionary pattern of CHIKV was analysed using the E1 protein gene through phylogenetic, Bayesian and Network methods with a dataset of 265 sequences from various countries. The time to most recent common ancestor of the virus was estimated to be 491 years ago with an evolutionary rate of 2.78 × 10−4 substitutions/site/year. Genetic characterisation of CHIKV strains was carried out in terms of variable sites, selection pressure and epitope mapping. The neutral selection pressure on the E1 gene of the virus suggested a stochastic process of evolution. We identified six potential epitope peptides in the E1 protein showing substantial interaction with human MHC-I and MHC-II alleles. The present study augments global epidemiological and population dynamics of CHIKV warranting undertaking of appropriate control measures. The identification of epitopic peptides can be useful in the development of epitope-based vaccine strategies against this re-emerging viral pathogen.
In this paper we develop an in-depth analysis of non-reversible Markov chains on denumerable state space from a similarity orbit perspective. In particular, we study the class of Markov chains whose transition kernel is in the similarity orbit of a normal transition kernel, such as that of birth–death chains or reversible Markov chains. We start by identifying a set of sufficient conditions for a Markov chain to belong to the similarity orbit of a birth–death chain. As by-products, we obtain a spectral representation in terms of non-self-adjoint resolutions of identity in the sense of Dunford [21] and offer a detailed analysis on the convergence rate, separation cutoff and L2-cutoff of this class of non-reversible Markov chains. We also look into the problem of estimating the integral functionals from discrete observations for this class. In the last part of this paper we investigate a particular similarity orbit of reversible Markov kernels, which we call the pure birth orbit, and analyse various possibly non-reversible variants of classical birth–death processes in this orbit.
When modelling subnational mortality rates, we should consider three features: (1) how to incorporate any possible correlation among subpopulations to potentially improve forecast accuracy through multi-population joint modelling; (2) how to reconcile subnational mortality forecasts so that they aggregate adequately across various levels of a group structure; (3) among the forecast reconciliation methods, how to combine their forecasts to achieve improved forecast accuracy. To address these issues, we introduce an extension of grouped univariate functional time-series method. We first consider a multivariate functional time-series method to jointly forecast multiple related series. We then evaluate the impact and benefit of using forecast combinations among the forecast reconciliation methods. Using the Japanese regional age-specific mortality rates, we investigate 1–15-step-ahead point and interval forecast accuracies of our proposed extension and make recommendations.
The prevalence of many diseases in pigs displays seasonal distributions. Despite growing concerns about the impacts of climate change, we do not yet have a good understanding of the role that weather factors play in explaining such seasonal patterns. In this study, national and county-level aggregated abattoir inspection data were assessed for England and Wales during 2010–2015. Seasonally-adjusted relationships were characterised between weekly ambient maximum temperature and the prevalence of both respiratory conditions and tail biting detected at slaughter. The prevalence of respiratory conditions showed cyclical annual patterns with peaks in the summer months and troughs in the winter months each year. However, there were no obvious associations with either high or low temperatures. The prevalence of tail biting generally increased as temperatures decreased, but associations were not supported by statistical evidence: across all counties there was a relative risk of 1.028 (95% CI 0.776–1.363) for every 1 °C fall in temperature. Whilst the seasonal patterns observed in this study are similar to those reported in previous studies, the lack of statistical evidence for an explicit association with ambient temperature may possibly be explained by the lack of information on date of disease onset. There is also the possibility that other time-varying factors not investigated here may be driving some of the seasonal patterns.
Norovirus (NoV) infections occur very frequently yet are rarely diagnosed. In Denmark, NoV infections are not under surveillance. We aimed to collect and describe existing laboratory-based NoV data. National NoV laboratory data were collected for 2011–2018, including information on patient identification number, age and sex, requesting physician, analysis date and result. We defined positive patient-episodes by using a 30-day time window and performed descriptive and time series analysis. Diagnostic methods used were assessed through a survey. We identified 15 809 patient-episodes (11%) out of 142 648 tested patients with an increasing trend, 9366 in 2011 vs. 32 260 in 2018. This corresponded with a gradual introduction of polymerase chain reaction analysis in laboratories. The highest positivity rate was in patients aged <5 years (15%) or >85 years (17%). There was a large difference in test performance over five Danish geographical regions and a marked seasonal variation with peaks from December to February. This is the first analysis of national NoV laboratory data in Denmark. A future laboratory-based surveillance system may benefit public health measures by describing trend, burden and severity of seasons and possibly pinpoint hospital outbreaks.
This retrospective study highlights the degree of losses and time-course through which the 2015 highly pathogenic avian influenza (HPAI) outbreaks in Ghana were managed. A total of 102 760 birds from 35 farms across five regions in Ghana included in this study were affected. Out of this, 89.3% was from the Greater Accra region. Majority of the birds were culled (94.2%). Adult layers were most affected and destroyed (64.0%), followed by broilers (13.7%). Event initiation to reporting averaged 7.7 ± 1.3 days (range: 1–30 days). Laboratory confirmation to depopulation of birds averaged 2.2 ± 0.5 (0–15) days while depopulation to disinfection took 2.2 ± 0.7 (0–20) days. Overall, some farms took as long as 30 days to report the outbreak to the authorities, 15 days from confirmation to depopulation and 20 days from depopulation to disinfection. On average, outbreak management lasted 12.3 (2–43) days from event initiation to depopulation. The study reveals a significant number of avian losses and delays in HPAI reporting and management by the authorities in Ghana during the 2015 outbreak. This poses a high risk of spread to other farms and a threat to public health. Awareness creation for poultry farmers is necessary for early reporting, while further study is required to set thresholds for the management of such outbreaks by veterinary departments.
We have previously shown that the Egyptian Hepatitis C Virus Risk Score (EGCRISC), an Egyptian hepatitis C virus (HCV) risk-based screening tool, to be valid and cost-effective. Certain behaviours, occupations and diseases have been shown to be associated with an increased risk of exposure to HCV infection and constitute a major population reservoir of HCV infection. This study investigated the efficacy of EGCRISC in selected high-risk groups by testing 863 participants from four groups: slaughterhouse workers, illicit drug users (IDUs), female sex workers and human immune deficiency virus (HIV) patients. Data for this study were collected on EGCRISC and another pre-designed risk factor questionnaire. Sera were tested for HCV antibodies by ELISA. EGCRISC, at lower cut-off points, showed significantly good performance (P < 0.05) in all four groups except for females <45 years, but was reliable in detecting HCV cases (sensitivity: 84.21% and negative predictive value: 94.5%). Specific scores for IDUs and HIV patients were developed that showed high accuracy (P < 0.001). A modified EGCRISC for high-risk groups (EGCRISC-HRGs) was shown to be a valid tool that is recommended for use in high-risk populations if no other specific screening tool is available or universal screening is applied. EGCRISC for IDUs (EGCRISC-IDUs) and EGCRISC for HIV patients (EGCRISC-HIV) are useful tools for preselecting potentially HCV-infected cases for further testing in settings where serological analysis is not readily available or accessible.
Influenza is a major human respiratory pathogen. Due to the high levels of influenza-like illness (ILI) in Zhejiang, China, the control and prevention of influenza was challenging during the 2017–2018 season. To identify the clinical spectrum of illness related to influenza and characterise the circulating influenza virus strains during this period, the characteristics of ILI were studied. Viral sequencing and phylogenetic analyses were conducted to investigate the virus types, substitutions at the amino acid level and phylogenetic relationships between sequences. This study has shown that the 2017/18 influenza season was characterised by the co-circulation of influenza A (H1N1) pdm09, A (H3N2) and B viruses (both Yamagata and Victoria lineage). From week 36 of 2017 to week 12 of 2018, ILI cases accounted for 5.58% of the total number of outpatient and emergency patient visits at the surveillance sites. Several amino acid substitutions were detected. Vaccination mismatch may be a potential reason for the high percentage of ILI. Furthermore, it is likely that multiple viral introductions played a role in the endemic co-circulation of influenza in Zhejiang, China. More detailed information regarding the molecular epidemiology of influenza should be included in long-term influenza surveillance.
A new fast-growing mycobacterium, designated strain QGD101T, was isolated from the sputum of an 84-year-old man suspected of tuberculosis in Wuhan Medical Treatment Center, Hubei, China. This strain was a gram-staining-negative, aerobic, non-spore-forming and catalase-positive bacterium, which was further identified as the NTM by PNB and TCH tests. The moxifloxacin and levofloxacin exhibited strong suppressing function against QGD101T with MIC values of 0.06 and 0.125 µg/ml after drug susceptibility testing of six main antimicrobial agents on mycobacteria. Based on the sequence analysis of 16S rRNA, rpoB, hsp65 and 16S-23S rRNA internal transcribed spacer, the strain QGD101T could not be identified to a species level. Mycobacterium moriokaense ATCC43059T that shared the highest 16S rRNA gene sequence similarity (98%) with strain QGD101T was actually different in genomes average nucleotide identity (78.74%). In addition, the major cellular fatty acids of QGD101T were determined as C18:1ω9c, C16:0 and C18:2ω6c. The DNA G + C content was 64.9% measured by high performance liquid chromatography. Therefore, the phenotypic and genotypic characterisation of this strain led us to the conclusion that it represents a novel species of mycobacteria, for which the name Mycobacterium hubeiense sp. nov. (type strain QGD101T = CCTCCAA 2017003T = KCTC39927T) was proposed. Thus, the results of this study are very significant for the clinical diagnosis of tuberculosis and future personalised medicine.
Transmission of varicella occurs frequently in schools and households. We investigated the characteristics of varicella cases derived from within-household transmission and the modes of varicella transmission between school and household settings in Shanghai, China, from 2009 to 2018. Within-household transmission occurred in 278 households, of which 134 transmission events were between children. Sixty-one household varicella transmission events may be attributed to isolation procedures for infected students during school outbreaks, and 7.6% of school outbreaks were caused by schoolchildren cases derived from within-household transmission. The frequency of ‘school-household-school’ transmission adds an additional layer of complexity to the control of school varicella outbreaks. Administration of varicella vaccine as post-exposure prophylaxis after exposure is considered to be an effective measure to control varicella spread within households and schools.
Log-concavity [log-convexity] and their various properties play an increasingly important role in probability, statistics, operations research and other fields. In this paper, we first establish general preservation theorems of log-concavity and log-convexity under operator $\phi \longmapsto T(\phi , \theta )=\mathbb {E}[\phi (X_\theta )]$, θ ∈ Θ, where Θ is an interval of real numbers or an interval of integers, and the random variable $X_\theta$ has a distribution function belonging to the family $\{F_\theta , \theta \in \Theta \}$ possessing the semi-group property. The proofs are based on the theory of stochastic comparisons and weighted distributions. The main results are applied to some special operators, for example, operators occurring in reliability, Bernstein-type operators and Beta-type operators. Several known results in the literature are recovered.
In recent years, there have been a significant influenza activity and emerging influenza strains in China, resulting in an increasing number of influenza virus infections and leading to public health concerns. The aims of this study were to identify the epidemiological and aetiological characteristics of influenza and establish seasonal autoregressive integrated moving average (SARIMA) models for forecasting the percentage of visits for influenza-like illness (ILI%) in urban and rural areas of Shenyang. Influenza surveillance data were obtained for ILI cases and influenza virus positivity from 18 sentinel hospitals. The SARIMA models were constructed to predict ILI% for January–December 2019. During 2010–2018, the influenza activity was higher in urban than in rural areas. The age distribution of ILI cases showed the highest rate in young children aged 0–4 years. Seasonal A/H3N2, influenza B virus and pandemic A/H1N1 continuously co-circulated in winter and spring seasons. In addition, the SARIMA (0, 1, 0) (0, 1, 2)12 model for the urban area and the SARIMA (1, 1, 1) (1, 1, 0)12 model for the rural area were appropriate for predicting influenza incidence. Our findings suggested that there were regional and seasonal distinctions of ILI activity in Shenyang. A co-epidemic pattern of influenza strains was evident in terms of seasonal influenza activity. Young children were more susceptible to influenza virus infection than adults. These results provide a reference for future influenza prevention and control strategies in the study area.