16 March 2015

Research Committee Articles, March 16, 2015

Devising an indicator to detect mid-term abortions in dairy cattle: A first step towards syndromic surveillance of abortive diseases

Bovine abortion surveillance is essential for human and animal health because it plays an important role in the early warning of several diseases. Due to the limited sensitivity of traditional surveillance systems, there is a growing interest for the devel opment of syndromic surveillance. Our objective was to assess whether, routinely collected, artificial insemination (AI) data could be used, as part of a syndromic surveillance system, to devise an indicator of mid-term abortions in dairy cattle herds in F rance. A mid-term abortion incidence rate (MAIR) was computed as the ratio of the number of mid-term abortions to the number of female- weeks at risk. A mid-term abortion was defined as a return-to-service (i.e. a new AI) taking place 90 to 180 days after the previous AI. Weekly variations in the MAIR in heifers and parous cows were modeled with a time-dependent Poisson model at the d├ępartement level (French administrative division) during the period of 2004 to 2010. The usefulness of monitoring this indica tor to detect a disease-related increase in mid-term abortions was evaluated using data from the 2007-2008 episode of bluetongue serotype 8 (BT8) in France. An increase in the MAIR was identified in heifers and parous cows in 47% (n = 24) and 71% (n = 39) of the d├ępartements. On average, the weekly MAIR among heifers increased by 3.8% (min-max: 0.02-57.9%) when the mean number of BT8 cases that occurred in the previous 8 to 13 weeks increased by one. The weekly MAIR among parous cows increased by 1.4% (0.01 -8.5%) when the mean number of BT8 cases occurring in the previous 6 to 12 weeks increased by one. These results underline the potential of the MAIR to identify an increase in mid-term abortions and suggest that it is a good candidate for the implementatio n of a syndromic surveillance system for bovine abortions.

Inference of seasonal and pandemic influenza transmission dynamics

The inference of key infectious disease epidemiological parameters is critical for characterizing disease spread and devising prevention and containment measures. The recent emergence of surveillance records mined from big data such as health-related onlin e queries and social media, as well as model inference methods, permits the development of new methodologies for more comprehensive estimation of these parameters. We use such data in conjunction with Bayesian inference methods to study the transmission dy namics of influenza. We simultaneously estimate key epidemiological parameters, including population susceptibility, the basic reproductive number, attack rate, and infectious period, for 115 cities during the 2003-2004 through 2012-2013 seasons, including the 2009 pandemic. These estimates discriminate key differences in the epidemiological characteristics of these outbreaks across 10 y, as well as spatial variations of influenza transmission dynamics among subpopulations in the United States. In addition, the inference methods appear to compensate for observational biases and underreporting inherent in the surveillance data.

Time series analyses of hand, foot and mouth disease integrating weather variables

Background: The past decade witnessed an increment in the incidence of hand foot mouth disease (HFMD) in the Pacific Asian region; specifically, in Guangzhou China. This emphasized the requirement of an early warning system designed to allow the medical co mmunity to better prepare for outbreaks and thus minimize the number of fatalities. Methods: Samples from 1,556 inpatients (hospitalized) and 11,004 outpatients (non-admitted) diagnosed with HFMD were collected in this study from January 2009 to October 20 13. Seasonal Autoregressive Integrated Moving Average (SARIMA) model was applied to establish high predictive model for inpatients and outpatient as well as three viral serotypes (EV71, Pan-EV and CA16). To integrate climate variables in the data analyses, data from eight climate variables were simultaneously obtained during this period. Significant climate variable identified by correlation analyses was executed to improve time series modeling as external repressors. Results: Among inpatients with HFMD, 24 8 (15.9%) were affected by EV71, 137 (8.8%) were affected by Pan-EV+, and 436 (28.0%) were affected by CA16. Optimal Univariate SARIMA model was identified: (2,0,3)(1,0,0)52 for inpatients, (0,1,0)(0,0,2)52 for outpatients as well as three serotypes (EV71, (1,0,1)(0,0,1)52; CA16, (1,0,1)(0,0,0)52; Pan-EV, (1,0,1) (0,0,0)52). Using climate as our independent variable, precipitation (PP) was first identified to be associated with inpatients (r = 0.211, P = 0.001), CA16-serotype (r = 0.171, P = 0.007) and outp atients (r = 0.214, P = 0.01) in partial correlation analyses, and was then shown a significant lag in cross-autocorrelation analyses. However, inclusion of PP [lag -3 week] as external repressor showed a moderate impact on the predictive performance of th e SARIMA model described here-in. Conclusion: Climate patterns and HFMD incidences have been shown to be strongly correlated. The SARIMA model developed here can be a helpful tool in developing an early warni

Spatial, temporal and genetic dynamics of highly pathogenic avian influenza A (H5N1) virus in China

Background: The spatial spread of H5N1 avian influenza, significant ongoing mutations, and long-term persistence of the virus in some geographic regions has had an enormous impact on the poultry industry and presents a serious threat to human health. Metho ds: We applied phylogenetic analysis, geospatial techniques, and time series models to investigate the spatiotemporal pattern of H5N1 outbreaks in China and the effect of vaccination on virus evolution. Results: Results showed obvious spatial and temporal clusters of H5N1 outbreaks on different scales, which may have been associated with poultry and wild-bird transmission modes of H5N1 viruses. Lead-lag relationships were found among poultry and wild-bird outbreaks and human cases. Human cases were preceded by poultry outbreaks, and wild-bird outbreaks were led by human cases. Each clade has gained its own unique spatiotemporal and genetic dominance. Genetic diversity of the H5N1 virus decreased significantly between 1996 and 2011; presumably under strong se lective pressure of vaccination. Mean evolutionary rates of H5N1 virus increased after vaccination was adopted in China. A clear signature of positively selected sites in the clade 2.3.2 virus was discovered and this may have resulted in the emergence of c lade 2.3.2.1. Conclusions: Our study revealed two different transmission modes of H5N1 viruses in China, and indicated a significant role of poultry in virus dissemination. Furthermore, selective pressure posed by vaccination was found in virus evolution i n the country.

Human brucellosis occurrences in inner mongolia, China: A spatio-temporal distribution and ecological niche modeling approach

Background: Brucellosis is a common zoonotic disease and remains a major burden in both human and domesticated animal populations worldwide. Few geographic studies of human Brucellosis have been conducted, especially in China. Inner Mongolia of China is co nsidered an appropriate area for the study of human Brucellosis due to its provision of a suitable environment for animals most responsible for human Brucellosis outbreaks. Methods: The aggregated numbers of human Brucellosis cases from 1951 to 2005 at the municipality level, and the yearly numbers and incidence rates of human Brucellosis cases from 2006 to 2010 at the county level were collected. Geographic Information Systems (GIS), remote sensing (RS) and ecological niche modeling (ENM) were integrated t o study the distribution of human Brucellosis cases over 1951-2010. Results: Results indicate that areas of central and eastern Inner Mongolia provide a long-term suitable environment where human Brucellosis outbreaks have occurred and can be expected to p ersist. Other areas of northeast China and central Mongolia also contain similar environments. Conclusions: This study is the first to combine advanced spatial statistical analysis with environmental modeling techniques when examining human Brucellosis out breaks and will help to inform decision-making in the field of public health.

Surveillance for severe acute respiratory infections (SARI) in hospitals in the WHO european region - an exploratory analysis of risk factors for a severe outcome in influenza-positive SARI cases

Background: The 2009 H1N1 pandemic highlighted the need to routinely monitor severe influenza, which lead to the establishment of sentinel hospital-based surveillance of severe acute respiratory infections (SARI) in several countries in Europe. The objecti ve of this study is to describe characteristics of SARI patients and to explore risk factors for a severe outcome in influenza-positive SARI patients. Methods: Data on hospitalised patients meeting a syndromic SARI case definition between 2009 and 2012 fro m nine countries in Eastern Europe (Albania, Armenia, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Romania, Russian Federation and Ukraine) were included in this study. An exploratory analysis was performed to assess the association between risk factors and a severe (ICU, fatal) outcome in influenza-positive SARI patients using a multivariate logistic regression analysis. Results: Nine countries reported a total of 13,275 SARI patients. The majority of SARI patients reported in these countries were young child ren. A total of 12,673 SARI cases (95%) were tested for influenza virus and 3377 (27%) were laboratory confirmed. The majority of tested SARI cases were from Georgia, the Russian Federation and Ukraine and the least were from Kyrgyzstan. The proportion pos itive varied by country, season and age group, with a tendency to a higher proportion positive in the 15+ yrs age group in six of the countries. ICU admission and fatal outcome were most often recorded for influenza-positive SARI cases aged > 15 yrs. An ex ploratory analysis using pooled data from influenza-positive SARI cases in three countries showed that age > 15yrs, having lung, heart, kidney or liver disease, and being pregnant were independently associated with a fatal outcome. Conclusions: Countries i n Eastern Europe have been able to collect data through routine monitoring of severe influenza and results on risk factors for a severe outcome in influenza-positive SARI cases have identified several risk gr

Meeting the International Health Regulations (2005) surveillance core capacity requirements at the subnational level in Europe: The added value of syndromic surveillance

Background: The revised World Health Organization's International Health Regulations (2005) request a timely and all-hazard approach towards surveillance, especially at the subnational level. We discuss three questions of syndromic surveillance application in the European context for assessing public health emergencies of international concern: (i) can syndromic surveillance support countries, especially the subnational level, to meet the International Health Regulations (2005) core surveillance capacity re quirements, (ii) are European syndromic surveillance systems comparable to enable cross-border surveillance, and (iii) at which administrative level should syndromic surveillance best be applied? Discussion: Despite the ongoing criticism on the usefulness of syndromic surveillance which is related to its clinically nonspecific output, we demonstrate that it was a suitable supplement for timely assessment of the impact of three different public health emergencies affecting Europe. Subnational syndromic surve illance analysis in some cases proved to be of advantage for detecting an event earlier compared to national level analysis. However, in many cases, syndromic surveillance did not detect local events with only a small number of cases. The European Commissi on envisions comparability of surveillance output to enable cross-border surveillance. Evaluated against European infectious disease case definitions, syndromic surveillance can contribute to identify cases that might fulfil the clinical case definition bu t the approach is too unspecific to comply to complete clinical definitions. Syndromic surveillance results still seem feasible for comparable cross-border surveillance as similarly defined syndromes are analysed. We suggest a new model of implementing syn dromic surveillance at the subnational level. In this model, syndromic surveillance systems are fine-tuned to their local context and integrated into the existing subnational surveillance and reporting struct

Influenza surveillance and forecast with smartphone sensors

In this paper we introduce an influenza surveillance and forecast system (ISFS) that can track the proliferation of influenza and predict potential infections by analyzing smartphone sensor readings. While previous studies investigate social connectivity t o deduce proliferation paths, we focus on the physical contacts of each individual that are the dominant cause of influenza infections. To estimate the probability of an infection through each physical contact we measure the surrounding features of each co ntact including the staying time of a contact, the human density and the openness of the space, and the infection status of each individual. By using a smartphone equipped with various sensors we can estimate the infection status of its owner by analyzing both the envelope of incoming sound and the surrounding features of the contact. A surveillance server, which aggregates the information from multiple smartphones, monitors the infection status of influenza and ranks both high risk persons and influential persons that have to be vaccinated promptly. To evaluate the forecast accuracy of ISFS we have implemented a full ISFS including an Android ISFS client and compare the forecast accuracy of ISFS against that of the traditional forecast system based on socia l connectivity. Our evaluation results suggest that influenza surveillance and forecast should be performed based on human activity rather than social connectivity. This would not only improve the forecast accuracy but it can also improve the cost efficien cy and the suppression effect of vaccinations by finding the most influential persons in the proliferation paths.

2014 MERS-CoV outbreak in Jeddah - A link to health care facilities

Background: A marked increase in the number of cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection occurred in Jeddah, Saudi Arabia, in early 2014. We evaluated patients with MERS-CoV infection in Jeddah to explore reasons for this i ncrease and to assess the epidemiologic and clinical features of this disease. Methods: We identified all cases of laboratory-confirmed MERS-CoV infection in Jeddah that were reported to the Saudi Arabian Ministry of Health from January 1 through May 16, 2 014. We conducted telephone interviews with symptomatic patients who were not health care personnel, and we reviewed hospital records. We identified patients who were reported as being asymptomatic and interviewed them regarding a history of symptoms in th e month before testing. Descriptive analyses were performed. Results: Of 255 patients with laboratory-confirmed MERS-CoV infection, 93 died (case fatality rate, 36.5%). The median age of all patients was 45 years (interquartile range, 30 to 59), and 174 pa tients (68.2%) were male. A total of 64 patients (25.1%) were reported to be asymptomatic. Of the 191 symptomatic patients, 40 (20.9%) were health care personnel. Among the 151 symptomatic patients who were not health care personnel, 112 (74.2%) had data t hat could be assessed, and 109 (97.3%) of these patients had had contact with a health care facility, a person with a confirmed case of MERS-CoV infection, or someone with severe respiratory illness in the 14 days before the onset of illness. The remaining 3 patients (2.7%) reported no such contacts. Of the 64 patients who had been reported as asymptomatic, 33 (52%) were interviewed, and 26 of these 33 (79%) reported at least one symptom that was consistent with a viral respiratory illness. Conclusions: The majority of patients in the Jeddah MERS-CoV outbreak had contact with a health care facility, other patients, or both. This highlights the role of health care-associated transmission.

Environmental Drivers of the Spatiotemporal Dynamics of Respiratory Syncytial Virus in the United States

Epidemics of respiratory syncytial virus (RSV) are known to occur in wintertime in temperate countries including the United States, but there is a limited understanding of the importance of climatic drivers in determining the seasonality of RSV. In the Uni ted States, RSV activity is highly spatially structured, with seasonal peaks beginning in Florida in November through December and ending in the upper Midwest in February-March, and prolonged disease activity in the southeastern US. Using data on both age- specific hospitalizations and laboratory reports of RSV in the US, and employing a combination of statistical and mechanistic epidemic modeling, we examined the association between environmental variables and state-specific measures of RSV seasonality. Tem perature, vapor pressure, precipitation, and potential evapotranspiration (PET) were significantly associated with the timing of RSV activity across states in univariate exploratory analyses. The amplitude and timing of seasonality in the transmission rate was significantly correlated with seasonal fluctuations in PET, and negatively correlated with mean vapor pressure, minimum temperature, and precipitation. States with low mean vapor pressure and the largest seasonal variation in PET tended to experience biennial patterns of RSV activity, with alternating years of “early-big” and “late-small” epidemics. Our model for the transmission dynamics of RSV was able to replicate these biennial transitions at higher amplitudes of seasonality in the transmission rat e. This successfully connects environmental drivers to the epidemic dynamics of RSV; however, it does not fully explain why RSV activity begins in Florida, one of the warmest states, when RSV is a winter-seasonal pathogen. Understanding and predicting the seasonality of RSV is essential in determining the optimal timing of immunoprophylaxis.

Development of a time-trend model for analyzing and predicting case-pattern of Lassa fever epidemics in Liberia, 2013-2017

Objective: The objective was to develop a case-pattern model for Lassa fever (LF) among humans and derive predictors of time-trend point distribution of LF cases in Liberia in view of the prevailing under-reporting and public health challenge posed by the disease in the country.

The Spatiotemporal Expansion of Human Rabies and Its Probable Explanation in Mainland China, 2004-2013

Background Human rabies is a significant public health concern in mainland China. However, the neglect of rabies expansion and scarce analyses of the dynamics have made the spatiotemporal spread pattern of human rabies and its determinants being poorly und erstood. Methods We collected geographic locations and timeline of reported human rabies cases, rabies sequences and socioeconomic variables for the years 2004-2013, and integrated multidisciplinary approaches, including epidemiological characterization, h otspots identification, risk factors analysis and phylogeographic inference, to explore the spread pattern of human rabies in mainland China during the last decade. Results The results show that human rabies distribution and hotspots were expanding from so utheastern regions to north or west regions, which could be associated with the evolution of the virus, especially the clade I-G. A Panel Poisson Regression analysis reveals that human rabies incidences had significant correlation with the education level, GDP per capita, temperature at one-month lag and canine rabies outbreak at two-month lag. Conclusions The reduction in the overall human rabies incidence was accompanied by a westward and northward expansion of the circulating region in mainland China. Hi gher risk of human rabies was associated with lower level of education and economic status. New clades of rabies, especial Clade I-G, played an important role in recent spread. Our findings provide valuable information for rabies control and prevention in the future.

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