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Introduction: Respondent-driven sampling (RDS) offers a recruitment strategy for hard-to-reach populations. However, RDS faces logistical and theoretical challenges that threaten efficiency and validity in settings worldwide. We present innovative adaptations to conventional RDS to overcome barriers encountered in recruiting a large, representative sample of men who have sex with men (MSM) who travel internationally. Methods: Novel methodological adaptations for the “International Travel Research to Inform Prevention” or “I-TRIP” study were offering participants a choice between electronic and paper coupons referrals for recruitment and modifying the secondary incentives structure from small cash amounts to raffle entries for periodic large cash prize raffle drawings. Staged referral limit increases from 3 to 10 referrals and progressive addition of 70 seeds were also implemented. Results: There were 501 participants enrolled in up to 13 waves of growth. Among participants with a choice of referral methods, 81% selected electronic referrals. Of participants who were recruited electronically, 90% chose to remain with electronic referrals when it was their turn to recruit. The mean number of enrolled referrals was 0.91 for electronic referrals compared to 0.56 for paper coupons. Median referral lag time, i.e., the time interval between when recruiters were given their referrals and when a referred individual enrolled in the study, was 20 days (IQR 10–40) for electronic referrals, 20 days (IQR 8–58) for paper coupons, 20 days (IQR 10–41) for raffle entries and 33 days (IQR 16–148) for small cash incentives. Conclusions: The recruitment of MSM who travel internationally required maximizing known flexible tools of RDS while at the same time necessitating innovations to increase recruitment efficiency. Electronic referrals emerged as a major advantage in recruiting this hard-to-reach population who are of high socio-economic status, geographically diffuse and highly mobile. These enhancements may improve the performance of RDS in target populations with similar characteristics. [ABSTRACT FROM AUTHOR]

Background: Around 67 million pets are owned by households in the United Kingdom, and an increasing number of these are exotic animals. Approximately a third of pets are purchased through retail outlets or direct from breeders. A wide range of infections can be associated with companion animals. Objectives: This study uses a systematic literature review to describe the transmission of zoonotic disease in humans associated with a pet shop or other location selling pets (incidents of rabies tracebacks and zoonoses from pet food were excluded). Data sources: PubMed and EMBASE. Results: Fifty seven separate case reports or incidents were described in the 82 papers that were identified by the systematic review. Summary information on each incident is included in this manuscript. The infections include bacterial, viral and fungal diseases and range in severity from mild to life threatening. Infections associated with birds and rodents were the most commonly reported. Over half of the reports describe incidents in the Americas, and three of these were outbreaks involving more than 50 cases. Many of the incidents identified relate to infections in pet shop employees. Limitations: This review may have been subject to publication bias, where unusual and unexpected zoonotic infections may be over-represented in peer-reviewed publications. It was also restricted to English-language articles so that pathogens that are more common in non-Western countries, or in more exotic animals not common in Europe and the Americas, may have been under-represented. Conclusions/implications: A wide spectrum of zoonotic infections are acquired from pet shops. Salmonellosis and psittacosis were the most commonly documented diseases, however more unusual infections such as tularemia also appeared in the review. Given their potential to spread zoonotic infection, it is important that pet shops act to minimise the risk as far as possible. [ABSTRACT FROM AUTHOR]

Background: A large proportion of patients receiving antiretroviral therapy (ART) in low and middle income countries (LMICs) have unknown treatment outcomes and are classified as lost to follow-up (LTFU). Physical tracing of patients classified as LTFU is common; however, effects of tracing on outcomes remains unclear. The objective of this systematic review is to compare estimates of LTFU, mortality and retention in LMIC in cohorts of patients with and without physical tracing. Methods and Findings: We systematically identified studies in LMIC programmatic settings using MEDLINE (2003–2011) and HIV conference abstracts (2009–2011). Studies reporting the proportion LTFU 12-months after ART initiation were included. Tracing activities were determined from manuscripts or by contacting study authors. Studies were classified as “tracing studies” if physical tracing was available for the majority of patients. Summary estimates from the 2 groups of studies (tracing and non-tracing) for LTFU, mortality, stop of ART, transfers out, and retention on ART were determined. 261 papers and 616 abstracts were identified of which 39 studies comprising 54 separate cohorts (n = 187,666) met inclusion criteria. Of those, physical tracing was available for 46% of cohorts. Treatment programs with physical tracing activities had lower estimated LTFU (7.6% vs. 15.1%; p<.001), higher estimated mortality (10.5% vs. 6.6%; p = .006), higher retention on ART (80.0 vs. 75.8%; p = .04) and higher retention at the original site (80.0% vs. 72.9%; p = .02). Conclusions: Knowledge of patient tracing is critical when interpreting program outcomes of LTFU, mortality and retention. The reduction of the proportion LTFU in tracing studies was only partially explained by re-classification of unknown outcomes. These data suggest that tracing may lead to increased re-engagement of patients in care, rather than just improved classification of unknown outcomes. [ABSTRACT FROM AUTHOR]

Knowledge of the incubation period of infectious diseases (time between host infection and expression of disease symptoms) is crucial to our epidemiological understanding and the design of appropriate prevention and control policies. Plant diseases cause substantial damage to agricultural and arboricultural systems, but there is still very little information about how the incubation period varies within host populations. In this paper, we focus on the incubation period of soilborne plant pathogens, which are difficult to detect as they spread and infect the hosts underground and above-ground symptoms occur considerably later. We conducted experiments on Rhizoctonia solani in sugar beet, as an example patho-system, and used modelling approaches to estimate the incubation period distribution and demonstrate the impact of differing estimations on our epidemiological understanding of plant diseases. We present measurements of the incubation period obtained in field conditions, fit alternative probability models to the data, and show that the incubation period distribution changes with host age. By simulating spatially-explicit epidemiological models with different incubation-period distributions, we study the conditions for a significant time lag between epidemics of cryptic infection and the associated epidemics of symptomatic disease. We examine the sensitivity of this lag to differing distributional assumptions about the incubation period (i.e. exponential versus Gamma). We demonstrate that accurate information about the incubation period distribution of a pathosystem can be critical in assessing the true scale of pathogen invasion behind early disease symptoms in the field; likewise, it can be central to model-based prediction of epidemic risk and evaluation of disease management strategies. Our results highlight that reliance on observation of disease symptoms can cause significant delay in detection of soil-borne pathogen epidemics and mislead practitioners and epidemiologists about the timing, extent, and viability of disease control measures for limiting economic loss. [ABSTRACT FROM AUTHOR]

No matching vaccine is immediately available when a novel influenza strain breaks out. Several nonvaccine-related strategies must be employed to control an influenza epidemic, including antiviral treatment, patient isolation, and immigration detection. This paper presents the development and application of two regional dynamic models of influenza with Pontryagin’s Maximum Principle to determine the optimal control strategies for an epidemic and the corresponding minimum antiviral stockpiles. Antiviral treatment was found to be the most effective measure to control new influenza outbreaks. In the case of inadequate antiviral resources, the preferred approach was the centralized use of antiviral resources in the early stage of the epidemic. Immigration detection was the least cost-effective; however, when used in combination with the other measures, it may play a larger role. The reasonable mix of the three control measures could reduce the number of clinical cases substantially, to achieve the optimal control of new influenza. [ABSTRACT FROM AUTHOR]

Individual behavioral response to the spreading of an epidemic plays a crucial role in the progression of the epidemic itself. The risk perception induces individuals to adopt a protective behavior, as for instance reducing their social contacts, adopting more restrictive hygienic measures or undergoing prophylaxis procedures. In this paper, starting with a previously developed lattice-gas SIR model, we construct a coupled behavior-disease model for influenza spreading with spontaneous behavioral changes. The focus is on self-initiated behavioral changes that alter the susceptibility to the disease, without altering the contact patterns among individuals. Three different mechanisms of awareness spreading are analyzed: the local spreading due to the presence in the neighborhood of infective individuals; the global spreading due to the news published by the mass media and to educational campaigns implemented at institutional level; the local spreading occurring through the “thought contagion” among aware and unaware individuals. The peculiarity of the present approach is that the awareness spreading model is calibrated on available data on awareness and concern of the population about the risk of contagion. In particular, the model is validated against the A(H1N1) epidemic outbreak in Italy during the season, by making use of the awareness data gathered by the behavioral risk factor surveillance system (PASSI). We find that, increasing the accordance between the simulated awareness spreading and the PASSI data on risk perception, the agreement between simulated and experimental epidemiological data improves as well. Furthermore, we show that, within our model, the primary mechanism to reproduce a realistic evolution of the awareness during an epidemic, is the one due to globally available information. This result highlights how crucial is the role of mass media and educational campaigns in influencing the epidemic spreading of infectious diseases. [ABSTRACT FROM AUTHOR]

In this study, we describe a novel porcine parechovirus-like virus (tentatively named PLV-CHN) from healthy piglets in China using 454 high-throughput sequencing. The complete genome of the virus comprises 6832 bp, encoding a predicted polyprotein of 2132 amino acids that is most similar to Ljungan virus (32% identity). A similar virus that belongs to a novel Picornaviridae genus, named swine pasivirus 1 (SPaV-1), was reported during the preparation of this paper. Sequence analysis revealed that PLV-CHN and SPaV1 shared 82% nucleotide identity and 89% amino acid identity. Further genomic and phylogenetic analyses suggested that both SPaV1 and PLV-CHN shared similar genomic characteristics and belong to the same novel Picornaviridae genus. A total of 36 (20.0%) fecal samples from 180 healthy piglets were positive for PLV-CHN by RT-PCR, while no fecal samples from 100 healthy children and 100 children with diarrhea, and no cerebrospinal fluid samples from 196 children with suspected viral encephalitis, was positive for the virus. However, Western blot and enzyme-linked immunosorbent assays using recombinant PLV-CHN VP1 polypeptide as an antigen showed a high seroprevalence of 63.5% in the healthy population. When grouped by age, the antibody-positivity rates showed that the majority of children under 12 years of age have been infected by the virus. It was suggested that PLV-CHN, SPaV1, or an as-yet-uncharacterized virus can infect humans early in life. Thus, investigation of the role of this novel virus is vital. [ABSTRACT FROM AUTHOR]

We consider the recently introduced edge-based compartmental models (EBCM) for the spread of susceptible-infected-recovered (SIR) diseases in networks. These models differ from standard infectious disease models by focusing on the status of a random partner in the population, rather than a random individual. This change in focus leads to simple analytic models for the spread of SIR diseases in random networks with heterogeneous degree. In this paper we extend this approach to handle deviations of the disease or population from the simplistic assumptions of earlier work. We allow the population to have structure due to effects such as demographic features or multiple types of risk behavior. We allow the disease to have more complicated natural history. Although we introduce these modifications in the static network context, it is straightforward to incorporate them into dynamic network models. We also consider serosorting, which requires using dynamic network models. The basic methods we use to derive these generalizations are widely applicable, and so it is straightforward to introduce many other generalizations not considered here. Our goal is twofold: to provide a number of examples generalizing the EBCM method for various different population or disease structures and to provide insight into how to derive such a model under new sets of assumptions. [ABSTRACT FROM AUTHOR]

One of network epidemiology's central assumptions is that the contact structure over which infectious diseases propagate can be represented as a static network. However, contacts are highly dynamic, changing at many time scales. In this paper, we investigate conceptually simple methods to construct static graphs for network epidemiology from temporal contact data. We evaluate these methods on empirical and synthetic model data. For almost all our cases, the network representation that captures most relevant information is a so-called exponential-threshold network. In these, each contact contributes with a weight decreasing exponentially with time, and there is an edge between a pair of vertices if the weight between them exceeds a threshold. Networks of aggregated contacts over an optimally chosen time window perform almost as good as the exponential-threshold networks. On the other hand, networks of accumulated contacts over the entire sampling time, and networks of concurrent partnerships, perform worse. We discuss these observations in the context of the temporal and topological structure of the data sets. [ABSTRACT FROM AUTHOR]

The Water-associated Disease Index (WADI) was developed to identify and visualize vulnerability to different water-associated diseases by integrating a range of social and biophysical determinants in map format. In this study vulnerability is used to encompass conditions of exposure, susceptibility, and differential coping capacity to a water-associated health hazard. By assessing these conditions, the tool is designed to provide stakeholders with an integrated and long-term understanding of subnational vulnerabilities to water-associated disease and contribute to intervention strategies to reduce the burden of illness. The objective of this paper is to describe and validate the WADI tool by applying it to dengue. A systemic ecohealth framework that considers links between people, the environment and health was applied to identify secondary datasets, populating the index with components including climate conditions, land cover, education status and water use practices. Data were aggregated to create composite indicators of exposure and of susceptibility in a Geographic Information System (GIS). These indicators were weighted by their contribution to dengue vulnerability, and the output consisted of an overall index visualized in map format. The WADI was validated in this Malaysia case study, demonstrating a significant association with dengue rates at a sub-national level, and illustrating a range of factors that drive vulnerability to the disease within the country. The index output indicated high vulnerability to dengue in urban areas, especially in the capital Kuala Lumpur and surrounding region. However, in other regions, vulnerability to dengue varied throughout the year due to the influence of seasonal climate conditions, such as monsoon patterns. The WADI tool complements early warning models for water-associated disease by providing upstream information for planning prevention and control approaches, which increasingly require a comprehensive and geographically broad understanding of vulnerability for implementation. [ABSTRACT FROM AUTHOR]

Batrachochytrium dendrobatidis is considered a main driver of the worldwide declines and extinctions of amphibian populations. Nonetheless, fundamental questions about its epidemiology, including whether it acts mainly as a “lone killer” or in conjunction with other factors, remain largely open. In this paper we analysed contemporary and historical samples of the endangered Apennine yellow-bellied toad (Bombina pachypus) along the Italian peninsula, in order to assess the presence of the pathogen and its spreading dynamics. Once common throughout its range, B. pachypus started to decline after the mid-1990s in the northern and central regions, whereas no declines have been observed so far in the southern region. We show that Batrachochytrium dendrobatidis is currently widespread along the entire peninsula, and that this was already so at least as early as the late 1970s, that is, well before the beginning of the observed declines. This temporal mismatch between pathogen occurrence and host decline, as well as the spatial pattern of the declines, suggests that the pathogen has not acted as a “lone killer”, but in conjunction with other factors. Among the potentially interacting factors, we identified two as the most probable, genetic diversity of host populations and recent climate changes. We discuss the plausibility of this scenario and its implications on the conservation of B. pachypus populations. [ABSTRACT FROM AUTHOR]

Accurate incidence forecasting of infectious disease is critical for early prevention and for better government strategic planning. In this paper, we present a comprehensive study of different forecasting methods based on the monthly incidence of typhoid fever. The seasonal autoregressive integrated moving average (SARIMA) model and three different models inspired by neural networks, namely, back propagation neural networks (BPNN), radial basis function neural networks (RBFNN), and Elman recurrent neural networks (ERNN) were compared. The differences as well as the advantages and disadvantages, among the SARIMA model and the neural networks were summarized and discussed. The data obtained for 2005 to 2009 and for 2010 from the Chinese Center for Disease Control and Prevention were used as modeling and forecasting samples, respectively. The performances were evaluated based on three metrics: mean absolute error (MAE), mean absolute percentage error (MAPE), and mean square error (MSE). The results showed that RBFNN obtained the smallest MAE, MAPE and MSE in both the modeling and forecasting processes. The performances of the four models ranked in descending order were: RBFNN, ERNN, BPNN and the SARIMA model. [ABSTRACT FROM AUTHOR]

Background: Mosquito-borne diseases are climate sensitive and there has been increasing concern over the impact of climate change on future disease risk. This paper projected the potential future risk of Barmah Forest virus (BFV) disease under climate change scenarios in Queensland, Australia. Methods/Principal Findings: We obtained data on notified BFV cases, climate (maximum and minimum temperature and rainfall), socio-economic and tidal conditions for current period 2000–2008 for coastal regions in Queensland. Grid-data on future climate projections for 2025, 2050 and 2100 were also obtained. Logistic regression models were built to forecast the otential risk of BFV disease distribution under existing climatic, socio-economic and tidal conditions. The model was applied to estimate the potential geographic distribution of BFV outbreaks under climate change scenarios. The predictive model had good model accuracy, sensitivity and specificity. Maps on potential risk of future BFV disease indicated that disease would vary significantly across coastal regions in Queensland by 2100 due to marked differences in future rainfall and temperature projections. Conclusions/Significance: We conclude that the results of this study demonstrate that the future risk of BFV disease would vary across coastal regions in Queensland. These results may be helpful for public health decision making towards developing effective risk management strategies for BFV disease control and prevention programs in Queensland. [ABSTRACT FROM AUTHOR]

Background: syndromic surveillance system has great advantages in promoting the early detection of epidemics and reducing the necessities of disease confirmation, and it is especially effective for surveillance in resource poor settings. However, most current syndromic surveillance systems are established in developed countries, and there are very few reports on the development of an electronic syndromic surveillance system in resource-constrained settings. Objective: this study describes the design and pilot implementation of an electronic surveillance system (ISS) for the early detection of infectious disease epidemics in rural China, complementing the conventional case report surveillance system. Methods: ISS was developed based on an existing platform ‘Crisis Information Sharing Platform’ (CRISP), combining with modern communication and GIS technology. ISS has four interconnected functions: 1) work group and communication group; 2) data source and collection; 3) data visualization; and 4) outbreak detection and alerting. Results: As of Jan. 31st 2012, ISS has been installed and pilot tested for six months in four counties in rural China. 95 health facilities, 14 pharmacies and 24 primary schools participated in the pilot study, entering respectively 74256, 79701, and 2330 daily records into the central database. More than 90% of surveillance units at the study sites are able to send daily information into the system. In the paper, we also presented the pilot data from health facilities in the two counties, which showed the ISS system had the potential to identify the change of disease patterns at the community level. Conclusions: The ISS platform may facilitate the early detection of infectious disease epidemic as it provides near real-time syndromic data collection, interactive visualization, and automated aberration detection. However, several constraints and challenges were encountered during the pilot implementation of ISS in rural China. [ABSTRACT FROM AUTHOR]

Methicillin resistant Staphylococcus aureus (MRSA) is currently a major cause of skin and soft tissue infections (SSTI) in the United States. Seasonal variation of MRSA infections in hospital settings has been widely observed. However, systematic time-series analysis of incidence data is desirable to understand the seasonality of community acquired (CA)-MRSA infections at the population level. In this paper, using data on monthly SSTI incidence in children aged 0–19 years and enrolled in Medicaid in Maricopa County, Arizona, from January 2005 to December 2008, we carried out time-series and nonlinear regression analysis to determine the periodicity, trend, and peak timing in SSTI incidence in children at different age: 0–4 years, 5–9 years, 10–14 years, and 15–19 years. We also assessed the temporal correlation between SSTI incidence and meteorological variables including average temperature and humidity. Our analysis revealed a strong annual seasonal pattern of SSTI incidence with peak occurring in early September. This pattern was consistent across age groups. Moreover, SSTIs followed a significantly increasing trend over the 4-year study period with annual incidence increasing from 3.36% to 5.55% in our pediatric population of approximately 290,000. We also found a significant correlation between the temporal variation in SSTI incidence and mean temperature and specific humidity. Our findings could have potential implications on prevention and control efforts against CA-MRSA. [ABSTRACT FROM AUTHOR]

Background: Recent focus on earlier detection of pathogen introduction in human and animal populations has led to the development of surveillance systems based on automated monitoring of health data. Real- or near real-time monitoring of pre-diagnostic data requires automated classification of records into syndromes–syndromic surveillance–using algorithms that incorporate medical knowledge in a reliable and efficient way, while remaining comprehensible to end users. Methods: This paper describes the application of two of machine learning (Naïve Bayes and Decision Trees) and rule-based methods to extract syndromic information from laboratory test requests submitted to a veterinary diagnostic laboratory. Results: High performance (F1-macro = 0.9995) was achieved through the use of a rule-based syndrome classifier, based on rule induction followed by manual modification during the construction phase, which also resulted in clear interpretability of the resulting classification process. An unmodified rule induction algorithm achieved an F1-micro score of 0.979 though this fell to 0.677 when performance for individual classes was averaged in an unweighted manner (F1-macro), due to the fact that the algorithm failed to learn 3 of the 16 classes from the training set. Decision Trees showed equal interpretability to the rule-based approaches, but achieved an F1-micro score of 0.923 (falling to 0.311 when classes are given equal weight). A Naïve Bayes classifier learned all classes and achieved high performance (F1-micro = 0.994 and F1-macro = .955), however the classification process is not transparent to the domain experts. Conclusion: The use of a manually customised rule set allowed for the development of a system for classification of laboratory tests into syndromic groups with very high performance, and high interpretability by the domain experts. Further research is required to develop internal validation rules in order to establish automated methods to update model rules without user input. [ABSTRACT FROM AUTHOR]

The dynamics of infectious diseases that are spread through direct contact have been proven to depend on the strength of community structure or modularity within the underlying network. It has been recently shown that weighted networks with similar modularity values may exhibit different mixing styles regarding the number of connections among communities and their respective weights. However, the effect of mixing style on epidemic behavior was still unclear. In this paper, we simulate the spread of disease within networks with different mixing styles: a dense-weak style (i.e., many edges among the communities with small weights) and a sparse-strong style (i.e., a few edges among the communities with large weights). Simulation results show that, with the same modularity: 1) the mixing style significantly influences the epidemic size, speed, pattern and immunization strategy; 2) the increase of the number of communities amplifies the effect of the mixing style; 3) when the mixing style changes from sparse-strong to dense-weak, there is a ‘saturation point’, after which the epidemic size and pattern become stable. We also provide a mean-field solution of the epidemic threshold and size on weighted community networks with arbitrary external and internal degree distribution. The solution explains the effect of the second moment of the degree distribution, and a symmetric effect of internal and external connections (incl. degree distribution and weight). Our study has both potential significance for designing more accurate metrics for the community structure and exploring diffusion dynamics on metapopulation networks. [ABSTRACT FROM AUTHOR]

The WHO recommended intervention of Directly Observed Treatment, Short-course (DOTS) appears to have been less successful than expected in reducing the burden of TB in some high prevalence settings. One strategy for enhancing DOTS is incorporating active case-finding through screening contacts of TB patients as widely used in low-prevalence settings. Predictive models that incorporate population-level effects on transmission provide one means of predicting impacts of such interventions. We aim to identify all TB transmission modelling studies addressing contact tracing and to describe and critically assess their modelling assumptions, parameter choices and relevance to policy. We searched MEDLINE, SCOPUS, COMPENDEX, Google Scholar and Web of Science databases for relevant English language publications up to February 2012. Of the 1285 studies identified, only 5 studies met our inclusion criteria of models of TB transmission dynamics in human populations designed to incorporate contact tracing as an intervention. Detailed implementation of contact processes was only present in two studies, while only one study presented a model for a high prevalence, developing world setting. Some use of relevant data for parameter estimation was made in each study however validation of the predicted impact of interventions was not attempted in any of the studies. Despite a large body of literature on TB transmission modelling, few published studies incorporate contact tracing. There is considerable scope for future analyses to make better use of data and to apply individual based models to facilitate more realistic patterns of infectious contact. Combined with a focus on high burden settings this would greatly increase the potential for models to inform the use of contract tracing as a TB control policy. Our findings highlight the potential for collaborative work between clinicians, epidemiologists and modellers to gather data required to enhance model development and validation and hence better inform future public health policy. [ABSTRACT FROM AUTHOR]

Several approaches have been proposed for near real-time detection and prediction of the spread of influenza. These include search query data for influenza-related terms, which has been explored as a tool for augmenting traditional surveillance methods. In this paper, we present a method that uses Internet search query data from Baidu to model and monitor influenza activity in China. The objectives of the study are to present a comprehensive technique for: (i) keyword selection, (ii) keyword filtering, (iii) index composition and (iv) modeling and detection of influenza activity in China. Sequential time-series for the selected composite keyword index is significantly correlated with Chinese influenza case data. In addition, one-month ahead prediction of influenza cases for the first eight months of 2012 has a mean absolute percent error less than 11%. To our knowledge, this is the first study on the use of search query data from Baidu in conjunction with this approach for estimation of influenza activity in China. [ABSTRACT FROM AUTHOR]

Sacbrood virus (SBV) is a picorna-like virus that affects honey bees (Apis mellifera) and results in the death of the larvae. Several procedures are available to detect Chinese SBV (CSBV) in clinical samples, but not to estimate the level of CSBV infection. The aim of this study was develop an assay for rapid detection and quantification of this virus. Primers and probes were designed that were specific for CSBV structural protein genes. A TaqMan minor groove binder (MGB) probe-based, fluorescence real-time quantitative PCR was established. The specificity, sensitivity and stability of the assay were assessed; specificity was high and there were no cross-reactivity with healthy larvae or other bee viruses. The assay was applied to detect CSBV in 37 clinical samples and its efficiency was compared with clinical diagnosis, electron microscopy observation, and conventional RT-PCR. The TaqMan MGB-based probe fluorescence real-time quantitative PCR for CSBV was more sensitive than other methods tested. This assay was a reliable, fast, and sensitive method that was used successfully to detect CSBV in clinical samples. The technology can provide a useful tool for rapid detection of CSBV. This study has established a useful protocol for CSBV testing, epidemiological investigation, and development of animal models. [ABSTRACT FROM AUTHOR]

We analysed an 11-year dataset (1998–2009) of Influenza-Like Illness (ILI) that was based on surveillance of ∽23% of Israel's population. We examined whether the level of synchrony of ILI epidemics in Israel's 12 largest cities is high enough to view Israel as a single epidemiological unit. Two methods were developed to assess the synchrony: (1) City-specific attack rates were fitted to a simple model in order to estimate the temporal differences in attack rates and spatial differences in reporting rates of ILI. The model showed good fit to the data (R2  =  0.76) and revealed considerable differences in reporting rates of ILI in different cities (up to a factor of 2.2). (2) A statistical test was developed to examine the null hypothesis (H0) that ILI incidence curves in two cities are essentially identical, and was tested using ILI data. Upon examining all possible pairs of incidence curves, 77.4% of pairs were found not to be different (H0 was not rejected). It was concluded that all cities generally have the same attack rate and follow the same epidemic curve each season, although the attack rate changes from season to season, providing strong support for the “Israel is one city” hypothesis. The cities which were the most out of synchronization were Bnei Brak, Beersheba and Haifa, the latter two being geographically remote from all other cities in the dataset and the former geographically very close to several other cities but socially separate due to being populated almost exclusively by ultra-orthodox Jews. Further evidence of assortative mixing of the ultra-orthodox population can be found in the 2001–2002 season, when ultra-orthodox cities and neighborhoods showed distinctly different incidence curves compared to the general population. [ABSTRACT FROM AUTHOR]

Background: Environmental nontuberculous mycobacteria (NTM) are ubiquitous organisms with which humans commonly interact. The epidemiologic characteristics of NTM diseases including mortality rate and its associated factors remain largely unknown. In this study, we explored the geographical area of exposure and mortality and comorbid conditions of affected persons to determine environment, host, and host-pathogen interactive factors. Methods: We analyzed mortality related to nontuberculous mycobacterial infections from 1999 through 2010 by examining multiple-cause-of-death data from the National Center for Health Statistics. Among those who died with these diseases, we analyzed age-adjusted mortality rates, trends, associations with demographic variables, and comorbid conditions and correlated this information with similar data for tuberculosis-related mortality during the same time. Measurements and Mean Results: From 1999 through 2010, nontuberculous mycobacterial disease was reported as an immediate cause of death in 2,990 people in the United States with a combined overall mean age-adjusted mortality rate of 0.1 per 100,000 person-years. A significant increase in the number of NTM related deaths was seen from 1999 through 2010 (R2 = 0.72, p<0.0001), but it was not significant after adjustment for age. Persons aged 55 years and older, women, those living in Hawaii and Louisiana, and those of non-Hispanic, white ethnicity had higher mortality rates. Compared to tuberculosis-related mortality, chronic obstructive pulmonary disease, bronchiectasis, HIV, interstitial lung diseases, and tobacco use were significantly more common in persons with nontuberculous mycobacteria-related deaths. Conclusions: Nontuberculous mycobacteria-related death numbers are rising and are unevenly distributed. The strong association of nontuberculous mycobacterial disease with age suggests that its prevalence will increase as the United States population ages. [ABSTRACT FROM AUTHOR]

Background: From 2007 to 2009, the Netherlands experienced a major Q fever epidemic, with higher hospitalization rates than the 2–5% reported in the literature for acute Q fever pneumonia and hepatitis. We describe epidemiological and clinical features of hospitalized acute Q fever patients and compared patients presenting with Q fever pneumonia with patients admitted for other forms of community-acquired pneumonia (CAP). We also examined whether proximity to infected ruminant farms was a risk factor for hospitalization. Methods: A retrospective cohort study was conducted for all patients diagnosed and hospitalized with acute Q fever between 2007 and 2009 in one general hospital situated in the high incidence area in the south of the Netherlands. Pneumonia severity scores (PSI and CURB-65) of acute Q fever pneumonia patients (defined as infiltrate on a chest x-ray) were compared with data from CAP patients. Hepatitis was defined as a >twofold the reference value for alanine aminotransferase and for bilirubin. Results: Among the 183 hospitalized acute Q fever patients, 86.0% had pneumonia. Elevated liver enzymes (alanine aminotransferase) were found in 32.3% of patients, although hepatitis was not observed in any of them. The most frequent clinical signs upon presentation were fever, cough and dyspnoea. The median duration of admission was five days. Acute Q fever pneumonia patients were younger, had less co-morbidity, and lower PSI and CURB-65 scores than other CAP patients. Anecdotal information from attending physicians suggests that some patients were admitted because of severe subjective dyspnoea, which was not included in the scoring systems. Proximity to an infected ruminant farm was not associated with hospitalization. Conclusion: Hospitalized Dutch acute Q fever patients mostly presented with fever and pneumonia. Patients with acute Q fever pneumonia were hospitalized despite low PSI and CURB-65 scores, presumably because subjective dyspnoea was not included in the scoring systems. [ABSTRACT FROM AUTHOR]

Genotyping of Klebsiella pneumoniae is indispensable for management of nosocomial infections, monitoring of emerging strains –including extended-spectrum beta-lactamase (ESBL) producers-, and general epidemiology. Such objectives require a high-resolution genotyping method with a fixed scheme that allows (1) long-term retrospective and prospective assessment, (2) objective result readout and (3) library storage for database development and exchangeable results. We have developed a multiple-locus variable number tandem repeat analysis (MLVA) using a single-tube fluorescently primed multiplex PCR for 8 Variable Number Tandem Repeats (VNTRs) and automated fragment size analysis. The type allocation scheme was optimized using 224 K. pneumoniae clinical isolates, which yielded 101 MLVA types. The method was compared to the gold standard multilocus sequence typing (MLST) using a subset of these clinical isolates (n = 95) and found to be highly concordant, with at least as high a resolution but with considerably less hands-on time. Our results position this MLVA scheme as an appropriate, high-throughput and relatively low-cost tool for K. pneumoniae epidemiology. [ABSTRACT FROM AUTHOR]

The Fever, Thrombocytopenia and Leukopenia Syndrome (FTLS) is caused by a bunyavirus known as the FTLS virus (FTLSV), which was recently discovered in China. We examined the epidemiological and etiological features of 637 laboratory-confirmed cases of FTLS with onset from January 2011 to December 2012 in Henan Province, China. The highest incidence of FTLS occurred between May and August: 76.5% of all laboratory-confirmed cases occurred during those four months. Of the laboratory-confirmed cases, 60.9% were in the 46–69 years old age groups; 96.1% (612/637) occurred in farmers; 98.1% (625/637) were reported from Xinyang Prefecture. During the same time period, 2047 cases were reported in China. The nucleotide and amino acid sequences of FTLSV strains identified during 2011–2012 in Henan Province were ≥96% identical. This findings provides insight for developing public-health interventions for the control and prevention of FTLS in epidemic area. [ABSTRACT FROM AUTHOR]

Background: Chagas disease caused by the protozoan Trypanosoma cruzi is an important public health problem in Latin America. The immunological mechanisms involved in Chagas disease pathogenesis remain incompletely elucidated. The aim of this study was to explore cytokine profiles and their possible association to the infecting DTU and the pathogenesis of Chagas disease. Methods: 109 sero-positive T. cruzi patients and 21 negative controls from Bolivia and Colombia, were included. Flow cytometry assays for 13 cytokines were conducted on human sera. Patients were divided into two groups: in one we compared the quantification of cytokines between patients with and without chronic cardiomyopathy; in second group we compared the levels of cytokines and the genetic variability of T. cruzi. Results: Significant difference in anti-inflammatory and pro-inflammatory cytokines profiles was observed between the two groups cardiac and non-cardiac. Moreover, serum levels of IFN-γ, IL-12, IL-22 and IL-10 presented an association with the genetic variability of T.cruzi, with significant differences in TcI and mixed infections TcI/TcII. Conclusion: Expression of anti-inflammatory and pro-inflammatory cytokines may play a relevant role in determining the clinical presentation of chronic patients with Chagas disease and suggests the occurrence of specific immune responses, probably associated to different T. cruzi DTUs. [ABSTRACT FROM AUTHOR]

Background: We investigated the relationship between average monthly temperature and the most common clinical pathogens causing infections in intensive care patients. Methods: A prospective unit-based study in 73 German intensive care units located in 41 different hospitals and 31 different cities with total 188,949 pathogen isolates (102,377 Gram-positives and 86,572 Gram-negatives) from 2001 to 2012. We estimated the relationship between the number of clinical pathogens per month and the average temperature in the month of isolation and in the month prior to isolation while adjusting for confounders and long-term trends using time series analysis. Adjusted incidence rate ratios for temperature parameters were estimated based on generalized estimating equation models which account for clustering effects. Results: The incidence density of Gram-negative pathogens was 15% (IRR 1.15, 95%CI 1.10–1.21) higher at temperatures ≥20°C than at temperatures below 5°C. E. cloacae occurred 43% (IRR = 1.43; 95%CI 1.31–1.56) more frequently at high temperatures, A. baumannii 37% (IRR = 1.37; 95%CI 1.11–1.69), S. maltophilia 32% (IRR = 1.32; 95%CI 1.12–1.57), K. pneumoniae 26% (IRR = 1.26; 95%CI 1.13–1.39), Citrobacter spp. 19% (IRR = 1.19; 95%CI 0.99–1.44) and coagulase-negative staphylococci 13% (IRR = 1.13; 95%CI 1.04–1.22). By contrast, S. pneumoniae 35% (IRR = 0.65; 95%CI 0.50–0.84) less frequently isolated at high temperatures. For each 5°C increase, we observed a 3% (IRR = 1.03; 95%CI 1.02–1.04) increase of Gram-negative pathogens. This increase was highest for A. baumannii with 8% (IRR = 1.08; 95%CI 1.05–1.12) followed by K. pneumoniae, Citrobacter spp. and E. cloacae with 7%. Conclusion: Clinical pathogens vary by incidence density with temperature. Significant higher incidence densities of Gram-negative pathogens were observed during summer whereas S. pneumoniae peaked in winter. There is increasing evidence that different seasonality due to physiologic changes underlies host susceptibility to different bacterial pathogens. Even if the underlying mechanisms are not yet clear, the temperature-dependent seasonality of pathogens has implications for infection control and study design. [ABSTRACT FROM AUTHOR]

Background: Higher plasma D-dimer levels are strong predictors of mortality in HIV+ individuals. The factors associated with D-dimer levels during HIV infection, however, remain poorly understood. Methods: In this cross-sectional study, participants in three randomized controlled trials with measured D-dimer levels were included (N = 9,848). Factors associated with D-dimer were identified by linear regression. Covariates investigated were: age, gender, race, body mass index, nadir and baseline CD4+ count, plasma HIV RNA levels, markers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6]), antiretroviral therapy (ART) use, ART regimens, co-morbidities (hepatitis B/C, diabetes mellitus, prior cardiovascular disease), smoking, renal function (estimated glomerular filtration rate [eGFR] and cystatin C) and cholesterol. Results: Women from all age groups had higher D-dimer levels than men, though a steeper increase of D-dimer with age occurred in men. Hepatitis B/C co-infection was the only co-morbidity associated with higher D-dimer levels. In this subgroup, the degree of hepatic fibrosis, as demonstrated by higher hyaluronic acid levels, but not viral load of hepatitis viruses, was positively correlated with D-dimer. Other factors independently associated with higher D-dimer levels were black race, higher plasma HIV RNA levels, being off ART at baseline, and increased levels of CRP, IL-6 and cystatin C. In contrast, higher baseline CD4+ counts and higher high-density lipoprotein cholesterol were negatively correlated with D-dimer levels. Conclusions: D-dimer levels increase with age in HIV+ men, but are already elevated in women at an early age due to reasons other than a higher burden of concomitant diseases. In hepatitis B/C co-infected individuals, hepatic fibrosis, but not hepatitis viral load, was associated with higher D-dimer levels. [ABSTRACT FROM AUTHOR]

Pneumococcal disease is frequent at the extremes of age. While several studies have looked at colonization among young children, much less is known among the elderly. We aimed to evaluate pneumococcal carriage among elderly adults living in Portugal. Between April 2010 and December 2012, nasopharyngeal and oropharyngeal swabs of adults over 60 years of age, living in an urban area (n = 1,945) or in a rural area (n = 1,416), were obtained. Pneumococci were isolated by culture-based standard procedures, identified by optochin susceptibility, bile solubility and PCR screening for lytA and cpsA, and characterized by antibiotype, serotype, and MLST. Associations between pneumococcal carriage, socio-demographic and clinical characteristics were evaluated by univariate analysis and multiple logistic regression. The global prevalence of carriage was 2.3% (95% CI: 1.8–2.8). In the multiple logistic regression analysis, smoking, being at a retirement home, and living in a rural area increased the odds of being a pneumococcal carrier by 4.4-fold (95% CI: 1.9–9.2), 2.0-fold (95% CI: 1.1–3.6) and 2.0-fold (95% CI: 1.2–3.5), respectively. Among the 77 pneumococcal isolates, 26 serotypes and 40 STs were identified. The most prevalent serotypes were (in decreasing order) 19A, 6C, 22F, 23A, 35F, 11A, and 23B, which accounted, in total, for 60.0% of the isolates. Most isolates (93.5%) had STs previously described in the MLST database. Resistance to macrolides, non-susceptibility to penicillin and multidrug resistance were found in 19.5%, 11.7%, and 15.6% of the isolates, respectively. We conclude that the prevalence of pneumococcal carriage in the elderly, in Portugal, as determined by culture-based methods, is low. Serotype and genotype diversity is high. Living in a rural area, in a retirement home, and being a smoker increased the risk of pneumococcal carriage. This study contributes to the establishment of a baseline that may be used to monitor how novel pneumococcal vaccines impact on colonization among the elderly. [ABSTRACT FROM AUTHOR]

Bovine tuberculosis is a bacterial disease caused by Mycobacterium bovis in livestock and wildlife with hosts that include Eurasian badgers (Meles meles), brushtail possum (Trichosurus vulpecula), and white-tailed deer (Odocoileus virginianus). Risk-assessment efforts in Michigan have been initiated on farms to minimize interactions of cattle with wildlife hosts but research on M. bovis on cattle farms has not investigated the spatial context of disease epidemiology. To incorporate spatially explicit data, initial likelihood of infection probabilities for cattle farms tested for M. bovis, prevalence of M. bovis in white-tailed deer, deer density, and environmental variables for each farm were modeled in a Bayesian hierarchical framework. We used geo-referenced locations of 762 cattle farms that have been tested for M. bovis, white-tailed deer prevalence, and several environmental variables that may lead to long-term survival and viability of M. bovis on farms and surrounding habitats (i.e., soil type, habitat type). Bayesian hierarchical analyses identified deer prevalence and proportion of sandy soil within our sampling grid as the most supported model. Analysis of cattle farms tested for M. bovis identified that for every 1% increase in sandy soil resulted in an increase in odds of infection by 4%. Our analysis revealed that the influence of prevalence of M. bovis in white-tailed deer was still a concern even after considerable efforts to prevent cattle interactions with white-tailed deer through on-farm mitigation and reduction in the deer population. Cattle farms test positive for M. bovis annually in our study area suggesting that the potential for an environmental source either on farms or in the surrounding landscape may contributing to new or re-infections with M. bovis. Our research provides an initial assessment of potential environmental factors that could be incorporated into additional modeling efforts as more knowledge of deer herd factors and cattle farm prevalence is documented. [ABSTRACT FROM AUTHOR]

Although human toxoplasmosis is a notifiable disease in Taiwan since 2007, little is known about its risk factors. This study aimed to investigate the risk factors for acute Toxoplasma gondii diseases in Taiwan. We conducted a nationwide population-based case-control study. Cases of acute human toxoplasmosis notified to the Taiwan Centers for Diseases Control (Taipei, Taiwan) during 2008–2013 were compared with controls that were randomly selected from healthy T. gondii-seronegative blood donors who participated in a nationwide T. gondii seroepidemiologic study during 2009–2010. Cases and controls were matched according to age, gender and residency at an 1∶8 ratio. Structured questionnaires were used to gather information regarding risk factors. A total of 30 laboratory-confirmed acute T. gondii disease cases and 224 controls were enrolled. The most common clinical manifestation of the cases was flu-like symptoms (n = 20), followed by central nervous system disease (n = 4), ocular diseases (n = 3), abortion (n = 2), and congenital infection (n = 1). Multivariate conditional logistic regression showed that raw clam consumption (adjusted odds ratio [OR] = 3.7; 95% confidence interval [CI] = 1.4–9.9) and having a cat in the household (adjusted OR = 2.9; 95% CI = 1.1–7.9) were two independent risk factors for acute T. gondii disease. We conclude that raw shellfish consumption and domestic cat exposure were risk factors for acquiring acute T. gondii diseases in Taiwan. This finding may guide future research and control policies. [ABSTRACT FROM AUTHOR]

Background: Nosocomial transmission has been implicated as a key factor in the outbreak of extensively drug resistant (XDR) and multidrug-resistant (MDR-TB) tuberculosis at Church of Scotland Hospital (CoSH), in KwaZulu-Natal (KZN), South Africa. The aim of this study was to quantify the burden of potentially infectious tuberculosis and the proportion of drug resistance among hospital inpatients throughout the province of KZN. Methods: Inpatients with current cough, capable of producing sputum were selected from 19 public hospitals in KZN. After informed consent, demographic and clinical data, and sputum samples were collected. Samples were processed for fluorescent microscopy, liquid culture and first and second-line anti-tuberculosis drug susceptibility testing. Results: There were a total of 2,964 inpatients where sampling was done. About 1,585 inpatients (53%) had a current cough and sufficient microbiological and clinical data for inclusion. Mycobacterium tuberculosis was isolated from 543 inpatients (34% of those tested and 18% of all inpatients). Eighty-four (15%) inpatients with TB were found to be MDR-TB infected and 16 (3%) had XDR-TB. There was no association between the prevalence of MDR-TB and proximity to CoSH. Among patients with microbiologically confirmed TB, MDR/XDR-TB was associated with male sex, a longer length of stay between hospital admission and date of sample collection, and current or previous TB treatment. Conclusions: One in five inpatients had potentially infectious TB. This is an underestimate since patients without current cough were not tested. MDR-TB was frequently observed and was found in nearly one in six active TB inpatients. While present at lower levels than the original outbreak report at CoSH, XDR-TB was detected in hospitals throughout KZN. The high burden of potentially infectious TB and confirmed MDR-TB, much of it undiagnosed, indicates a serious risk for nosocomial transmission and the need for intensified infection control within the inpatient setting. [ABSTRACT FROM AUTHOR]

Objective: To examine HIV prevalence, HIV testing behaviour, undiagnosed infection and risk factors for HIV positivity among a community sample of gay men in Scotland. Methods: Cross-sectional survey of gay and bisexual men attending commercial gay venues in Glasgow and Edinburgh, Scotland with voluntary anonymous HIV testing of oral fluid samples in 2011. A response rate of 65.2% was achieved (1515 participants). Results: HIV prevalence (4.8%, 95% confidence interval, CI 3.8% to 6.2%) remained stable compared to previous survey years (2005 and 2008) and the proportion of undiagnosed infection among HIV-positive men (25.4%) remained similar to that recorded in 2008. Half of the participants who provided an oral fluid sample stated that they had had an HIV test in the previous 12 months; this proportion is significantly higher when compared to previous study years (50.7% versus 33.8% in 2005, p<0.001). Older age (>25 years) was associated with HIV positivity (1.8% in those <25 versus 6.4% in older ages group) as was a sexually transmitted infection (STI) diagnosis within the previous 12 months (adjusted odds ratio 2.13, 95% CI 1.09–4.14). There was no significant association between age and having an STI or age and any of the sexual behaviours recorded. Conclusion: HIV transmission continues to occur among gay and bisexual men in Scotland. Despite evidence of recent testing within the previous six months, suggesting a willingness to test, the current opt-out policy may have reached its limit with regards to maximising HIV test uptake. Novel strategies are required to improve regular testing opportunities and more frequent testing as there are implications for the use of other biomedical HIV interventions. [ABSTRACT FROM AUTHOR]

Background: Pharyngeal bacteria are exposed to different sugar conditions depending on the diet of the child. We hypothesized that dietary factors such as daily intake of carbohydrates could be associated with pneumococcal carriage and the occurrence of otitis media in children. Methods: Our study design was a cross-sectional study among 1006 children attending child day care centers. Parents filled in a food frequency questionnaire. Oropharyngeal swabs were collected from each child. The primary outcome was the occurrence of pneumococcal carriage and the secondary outcome the number of acute otitis media episodes during life. Principal component analysis was used to group dietary intake into nine factors. The models were adjusted for age, gender of the child and educational level of the mother. Results: The dietary factor which included high consumption of sweet pastries and jam was associated with an increased risk of pneumococcal carriage (OR 1.17, 95% CI 1.01 to 1.36, P-value 0.04). The factor including frequent consumption of fruit and berries was associated with a decreased risk of acute otitis (regression coefficient −0.51, 95% CI −0.98 to −0.03, P = 0.04). A high intake of consumption of sweets and snacks (OR 1.36, 95% CI 1.03 to 1.80, P = 0.03) was associated with an increased risk of caries. Conclusions: Diet was associated with a risk of pneumococcal carriage and the occurrence of otitis media. Diet may thus be a modifiable risk factor for the occurrence of acute otitis media. [ABSTRACT FROM AUTHOR]

RSV is the leading cause of lower respiratory-tract infections in infants and therefore demands in-depth epidemiological characterization. We investigated here the distribution of RSV types in Israel between the years 2005–2012. Clinical samples were collected from 11,018 patients hospitalized due to respiratory illnesses and were evaluated for the presence of various respiratory viruses, including RSV A and RSV B. Until 2008, each year was characterized by the presence of one dominant type of RSV. However, from 2008, both RSV A and B types were detected at significant levels, particularly among infants aged 0–2 years. Furthermore, significant changes in the RSV A and RSV B subtypes circulating in Israel since 2008 were observed. Finally, we demonstrate that, irrespectively of the changes observed in RSV epidemiology, when the pandemic H1N1pdm09 influenza virus appeared in 2009, RSV infections were delayed and were detected when infection with H1N1pdm09 had declined. [ABSTRACT FROM AUTHOR]

Background: Countries face conflicting incentives to report infectious disease outbreaks. Reports of outbreaks can prompt other countries to impose trade and travel restrictions, which has the potential to discourage reporting. However, reports can also bring medical assistance to contain the outbreak, including access to vaccines. Methods: We compiled data on reports of meningococcal meningitis to the World Health Organization (WHO) from 54 African countries between 1966 and 2002, a period is marked by two events: first, a large outbreak reported from many countries in 1987 associated with the Hajj that resulted in more stringent requirements for meningitis vaccination among pilgrims; and second, another large outbreak in Sub-Saharan Africa in 1996 that led to a new international mechanism to supply vaccines to countries reporting a meningitis outbreak. We used fixed-effects regression modeling to statistically estimate the effect of external forcing events on the number of countries reporting cases of meningitis to WHO. Findings: We find that the Hajj vaccination requirements started in 1988 were associated with reduced reporting, especially among countries with relatively fewer cases reported between 1966 and 1979. After the vaccine provision mechanism was in place in 1996, reporting among countries that had previously not reported meningitis outbreaks increased. Interpretation: These results indicate that countries may respond to changing incentives to report outbreaks when they can do so. In the long term, these incentives are likely to be more important than surveillance assistance in prompt reporting of outbreaks. [ABSTRACT FROM AUTHOR]

This cross-sectional study was carried out to explore the epidemiological and clinical features of dengue fever in Faisalabad, Pakistan during 2011 and 2012. During the study period, anti-dengue IgM positive cases were reported in the post-monsoon period during the months of August–December. Certain hotspots for the dengue infection were identified in the city that coincide with the clusters of densely populated urban regions of the city. Out of total 299 IgM positive patients (male 218 and female 81); there were 239 dengue fever (DF) and 60 dengue hemorrhagic fever (DHF) patients. There was decrease in the median age of dengue patients from 31 years in 2011 to 21.5 years in 2012 (p<0.001). Abdominal pain was seen in 35% DHF patients followed by nausea in 28.3%, epistaxis in 25% and rash in 20% patients (p<0.05). Patients reported to be suffering from high-grade fever for an average of 8.83 days in DHF as compared to 5.82 days in DF before being hospitalized. Co-morbidities were found to be risk factor for the development of DHF in dengue patients. Clinical and laboratory features of dengue cases studied could be used for the early identification of patients at risk of severe dengue fever. [ABSTRACT FROM AUTHOR]

Background: Little is known about risk factors for severe outcomes in patients infected with H5N1 and no systematic review has been conducted. Understanding risk factors is an important step for prioritizing prophylaxis or treatment in the event of a pandemic. Objectives: To systematically evaluate risk factors for severe outcomes in patients with avian influenza H5N1 infection. Data sources: MEDLINE, EMBASE, CINAHL, GlobalHealth, and CENTRAL through March 2011 Eligibility criteria for selecting studies: Observational studies of any design published in English, French, Spanish, German or Korean that reported on risk factor-outcome combinations of interest in participants with confirmed H5N1 infections. Outcomes considered included death, ventilator support, hospital and ICU admission, pneumonia, and composite outcomes. Study appraisal: Risk of bias was assessed using the Newcastle-Ottawa scale (NOS). Results: We identified 20 studies reporting on 999 patients infected with H5N1. The majority of studies (n = 14, 70%) were at intermediate risk of bias, i.e. 4–6 points on the NOS. Females were at increased risk of death (OR 1.75, 95% CI 1.27–2.44), while young age, in particular <5 years of age (OR 0.44, 95% CI 0.25–0.79 for death), was protective. Data on traditional risk factors was scarce and requires further studies. Another major limitation in the published literature was lack of adjustment for confounders. Interpretation: Females were at increased risk for complications following H5N1 infection while young age protected against severe outcomes. Research on traditional risk factors was limited and is required. [ABSTRACT FROM AUTHOR]

In recent years, a number of zoonotic flaviviruses have emerged worldwide, and wild birds serve as their major reservoirs. Epidemiological surveys of bird populations at various geographical scales can clarify key aspects of the eco-epidemiology of these viruses. In this study, we aimed at exploring the presence of flaviviruses in the western Mediterranean by sampling breeding populations of the yellow-legged gull (Larus michahellis), a widely distributed, anthropophilic, and abundant seabird species. For 3 years, we sampled eggs from 19 breeding colonies in Spain, France, Algeria, and Tunisia. First, ELISAs were used to determine if the eggs contained antibodies against flaviviruses. Second, neutralization assays were used to identify the specific flaviviruses present. Finally, for colonies in which ELISA-positive eggs had been found, chick serum samples and potential vectors, culicid mosquitoes and soft ticks (Ornithodoros maritimus), were collected and analyzed using serology and PCR, respectively. The prevalence of flavivirus-specific antibodies in eggs was highly spatially heterogeneous. In northeastern Spain, on the Medes Islands and in the nearby village of L'Escala, 56% of eggs had antibodies against the flavivirus envelope protein, but were negative for neutralizing antibodies against three common flaviviruses: West Nile, Usutu, and tick-borne encephalitis viruses. Furthermore, little evidence of past flavivirus exposure was obtained for the other colonies. A subset of the Ornithodoros ticks from Medes screened for flaviviral RNA tested positive for a virus whose NS5 gene was 95% similar to that of Meaban virus, a flavivirus previously isolated from ticks of Larus argentatus in western France. All ELISA-positive samples subsequently tested positive for Meaban virus neutralizing antibodies. This study shows that gulls in the western Mediterranean Basin are exposed to a tick-borne Meaban-like virus, which underscores the need of exploring the spatial and temporal distribution of this flavivirus as well as its potential pathogenicity for animals and humans. [ABSTRACT FROM AUTHOR]

Background: To estimate the incidence of Hepatitis C virus (HCV) and the predictive factors through repeated routine laboratory analyses. Methods: An observational cohort study was carried out in Quatre Camins Prison, Barcelona. The study included subjects with an initial negative HCV result and routine laboratory analyses containing HCV serology from 1992 to 2011. The incidence of infection was calculated for the study population and for sub-groups by 100 person-years of follow-up (100 py). The predictive factors were determined through Kaplan-Meier curves and a Cox regression. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated. Results: A total of 2,377 prisoners were included with a median follow-up time of 1,540.9 days per patient. Among the total population, 117 HCV seroconversions were detected (incidence of 1.17/100 py). The incidence was higher between 1992 and 1995 (2.57/100 py), among cases with HIV co-infection (8.34/100 py) and among intravenous drug users (IDU) without methadone treatment (MT) during follow-up (6.66/100 py). The incidence rate of HCV seroconversion among cases with a history of IDU and current MT was 1.35/100 py, which is close to that of the total study population. The following variables had a positive predictive value for HCV infection: IDU (p<0.001; HR = 7,30; CI: 4.83–11.04), Spanish ethnicity (p = 0.009; HR = 2,03; CI: 1.93–3.44) and HIV infection (p = 0.015; HR = 1.97; CI: 1.14–3.39). Conclusion: The incidence of HCV infection among prisoners was higher during the first part of the study and among IDU during the entire study period. Preventative programs should be directed toward this sub-group of the prison population. [ABSTRACT FROM AUTHOR]

Despite increasing control measures, numerous parasitic and infectious diseases are emerging, re-emerging or causing recurrent outbreaks particularly in Asia and the Pacific region, a hot spot of both infectious disease emergence and biodiversity at risk. We investigate how biodiversity affects the distribution of infectious diseases and their outbreaks in this region, taking into account socio-economics (population size, GDP, public health expenditure), geography (latitude and nation size), climate (precipitation, temperature) and biodiversity (bird and mammal species richness, forest cover, mammal and bird species at threat). We show, among countries, that the overall richness of infectious diseases is positively correlated with the richness of birds and mammals, but the number of zoonotic disease outbreaks is positively correlated with the number of threatened mammal and bird species and the number of vector-borne disease outbreaks is negatively correlated with forest cover. These results suggest that, among countries, biodiversity is a source of pathogens, but also that the loss of biodiversity or its regulation, as measured by forest cover or threatened species, seems to be associated with an increase in zoonotic and vector-borne disease outbreaks. [ABSTRACT FROM AUTHOR]

Background: Better understanding the etiology-specific incidence of severe acute respiratory infections (SARIs) in resource-poor, rural settings will help further develop and prioritize prevention strategies. To address this gap in knowledge, we conducted a longitudinal study to estimate the incidence of SARIs among children in rural Bangladesh. Methods: During June through October 2010, we followed children aged <5 years in 67 villages to identify those with cough, difficulty breathing, age-specific tachypnea and/or danger signs in the community or admitted to the local hospital. A study physician collected clinical information and obtained nasopharyngeal swabs from all SARI cases and blood for bacterial culture from those hospitalized. We tested swabs for respiratory syncytial virus (RSV), influenza viruses, human metapneumoviruses, adenoviruses and human parainfluenza viruses 1–3 (HPIV) by real-time reverse transcription polymerase chain reaction. We calculated virus-specific SARI incidence by dividing the number of new illnesses by the person-time each child contributed to the study. Results: We followed 12,850 children for 279,029 person-weeks (pw) and identified 141 SARI cases; 76 (54%) at their homes and 65 (46%) at the hospital. RSV was associated with 7.9 SARI hospitalizations per 100,000 pw, HPIV3 2.2 hospitalizations/100,000 pw, and influenza 1.1 hospitalizations/100,000 pw. Among non-hospitalized SARI cases, RSV was associated with 10.8 illnesses/100,000 pw, HPIV3 1.8/100,000 pw, influenza 1.4/100,000 pw, and adenoviruses 0.4/100,000 pw. Conclusion: Respiratory viruses, particularly RSV, were commonly associated with SARI among children. It may be useful to explore the value of investing in prevention strategies, such as handwashing and respiratory hygiene, to reduce respiratory infections among young children in such settings. [ABSTRACT FROM AUTHOR]

Background: Sexually transmitted infections (STIs), including Hepatitis B and C virus, are emerging public health risks in China, especially among men who have sex with men (MSM). This study aims to assess the magnitude and risks of STIs among Chinese MSM. Methods: Chinese and English peer-reviewed articles were searched in five electronic databases from January 2000 to February 2013. Pooled prevalence estimates for each STI infection were calculated using meta-analysis. Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were obtained. This review followed the PRISMA guidelines and was registered in PROSPERO. Results: Eighty-eight articles (11 in English and 77 in Chinese) investigating 35,203 MSM in 28 provinces were included in this review. The prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5–11.0%) for chlamydia, 1.5% (0.7–2.9%) for genital wart, 1.9% (1.3–2.7%) for gonorrhoea, 8.9% (7.8–10.2%) for hepatitis B (HBV), 1.2% (1.0–1.6%) for hepatitis C (HCV), 66.3% (57.4–74.1%) for human papillomavirus (HPV), 10.6% (6.2–17.6%) for herpes simplex virus (HSV-2) and 4.3% (3.2–5.8%) for Ureaplasma urealyticum. HIV-positive MSM have consistently higher odds of all these infections than the broader MSM population. As a subgroup of MSM, MSW were 2.5 (1.4–4.7), 5.7 (2.7–12.3), and 2.2 (1.4–3.7) times more likely to be infected with chlamydia, gonorrhoea and HCV than the broader MSM population, respectively. Conclusion: Prevalence levels of STIs among MSW were significantly higher than the broader MSM population. Co-infection of HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs healthcare and surveillance systems is essential in providing effective HIV/STIs preventive measures and treatments. Trial Registration: PROSPERO No: CRD42013003721 [ABSTRACT FROM AUTHOR]

Factor H-Binding Protein (fHbp) is an outer membrane protein antigen included in two novel meningococcal group B vaccines and, as such, is an important typing target. Approximately 50% of meningococcal disease cases in England and Wales are confirmed using real-time PCR on non-culture clinical specimens only. Protocols for typing fHbp from this subset of cases have not yet been established. Here we present a nested PCR-based assay designed to amplify and sequence fHbp from non-culture clinical specimens. From analytical sensitivity experiments carried out using diluted DNA extracts, an estimated analytical sensitivity limit of 6 fg/µL of DNA (<3 genome copies/µL) was calculated. The sensitivity of the assay was shown to be comparable to the ctrA-directed real-time PCR assay currently used to confirm invasive disease diagnoses from submitted clinical specimens. A panel of 96 diverse, patient-matched clinical specimen/isolate pairs from invasive disease cases was used to illustrate the breadth of strain coverage for the assay. All fHbp alleles sequenced from the isolates matched those derived from previous whole genome analyses. The first-round PCR primer binding sites are highly conserved, however an exceptional second-round PCR primer site mismatch in one validation isolate prevented amplification. In this case, amplification from the corresponding clinical specimen was achieved, suggesting that the use of a nested PCR procedure may compensate for any minor mismatches in round-two primer sites. The assay was successful at typing 91/96 (94.8%) of the non-culture clinical specimens in this study and exhibits sufficient sensitivity to type fHbp from the vast majority of non-culture clinical specimens received by the Meningococcal Reference Unit, Public Health England. [ABSTRACT FROM AUTHOR]