Naturally occurring fire coral clones demonstrate a genetic and environmental basis of microbiome composition.

Coral microbiomes are critical to holobiont functioning, but much remains to be understood about how prevailing environment and host genotype affect microbial communities in ecosystems. Resembling human identical twin studies, we examined bacterial community differences of naturally occurring fire coral clones within and between contrasting reef habitats to assess the relative contribution of host genotype and environment to microbiome structure. Bacterial community composition of coral clones differed between reef habitats, highlighting the contribution of the environment. Similarly, but to a lesser extent, microbiomes varied across different genotypes in identical habitats, denoting the influence of host genotype. Predictions of genomic function based on taxonomic profiles suggest that environmentally determined taxa supported a functional restructuring of the microbial metabolic network. In contrast, bacteria determined by host genotype seemed to be functionally redundant. Our study suggests microbiome flexibility as a mechanism of environmental adaptation with association of different bacterial taxa partially dependent on host genotype.

Evaluating vaccination strategies to control foot-and-mouth disease: a country comparison study.

Vaccination is increasingly being recognised as a potential tool to supplement 'stamping out' for controlling foot-and-mouth disease (FMD) outbreaks in non-endemic countries. Infectious disease simulation models provide the opportunity to determine how vaccination might be used in the face of an FMD outbreak. Previously, consistent relative benefits of specific vaccination strategies across different FMD simulation modelling platforms have been demonstrated, using a UK FMD outbreak scenario. We extended this work to assess the relative effectiveness of selected vaccination strategies in five countries: Australia, New Zealand, the USA, the UK and Canada. A comparable, but not identical, FMD outbreak scenario was developed for each country with initial seeding of Pan Asia type O FMD virus into an area with a relatively high density of livestock farms. A series of vaccination strategies (in addition to stamping out (SO)) were selected to evaluate key areas of interest from a disease response perspective, including timing of vaccination, species considerations (e.g. vaccination of only those farms with cattle), risk area vaccination and resources available for vaccination. The study found that vaccination used with SO was effective in reducing epidemic size and duration in a severe outbreak situation. Early vaccination and unconstrained resources for vaccination consistently outperformed other strategies. Vaccination of only those farms with cattle produced comparable results, with some countries demonstrating that this could be as effective as all species vaccination. Restriction of vaccination to higher risk areas was less effective than other strategies. This study demonstrates consistency in the relative effectiveness of selected vaccination strategies under different outbreak start up conditions conditional on the assumption that each of the simulation models provide a realistic estimation of FMD virus spread. Preferred outbreak management approaches must however balance the principles identified in this study, working to clearly defined outbreak management objectives, while having a good understanding of logistic requirements and the socio-economic implications of different control measures.

Patterns of intra-articular injection use after initiation of treatment in patients with knee osteoarthritis: data from the osteoarthritis initiative.

OBJECTIVE: We sought to describe and evaluate longitudinal use of intra-articular injections after treatment initiation among adults with radiographically confirmed knee osteoarthritis (OA). METHOD: Using data from the Osteoarthritis Initiative (OAI), we included participants with radiographically confirmed OA (Kellgren-Lawrence grade (K-L) ≥ 2) in ≥1 knee at baseline. With 9 years of data, 412 participants newly initiating hyaluronic acid or corticosteroid injections with their index visit were identified. For each type of injection initiated, socio-demographic and clinical characteristics were described by patterns of treatments (one-time use, switched, or continued injections). Multinomial logistic models estimated the extent to which patient-reported symptoms (post-initial injection and changes over time) were associated with patterns of injection use. RESULTS: Of those initiating injections, ∼19% switched, ∼21% continued injection type, and ∼60% did not report any additional injections. For participants initiating corticosteroid injections, greater symptoms post-initial injection were associated with lower odds of continued use compared to one-time users (adjusted odds ratio (aOR) for Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain: 0.91; 95%, confidence interval (CI): 0.83 to 0.99; aORstiffness: 0.77; CI: 0.63 to 0.94; aORphysical function: 0.97; CI: 0.94 to 1.00). Symptom changes over time (e.g., worsened or improved) were not associated with patterns of injections use. CONCLUSION: After treatment initiation, the proportion of patients switching injection use and one-time users was substantial. Symptoms post-initial injection appear to be associated with patterns of injection use. The extent to which these patterns are an indication of lack of impact on patient-reported symptoms should be explored.

Assessment of Effectiveness of Control Strategies Against Simulated Outbreaks of Highly Pathogenic Avian Influenza in Ontario, Canada.

The North American Animal Disease Spread Model (NAADSM) is a stochastic model framework developed to simulate the spread of highly contagious diseases of livestock and poultry, such as foot-and-mouth disease and highly pathogenic avian influenza (HPAI). The objective of this study was to make recommendations on the most effective HPAI control policy for Canada, specifically, on the effect of different speeds of detection, effectiveness of movement restrictions and stamping-out and ring-culling strategies on the magnitude of an HPAI outbreak. In addition, the effect of introduction of infection in a range of multiple farms simultaneously was also evaluated. A total of 21 060 scenarios, defined as different combinations of parameters for various epidemiological conditions and control measures, were created to simulate the number of poultry flocks that would become infected as a result of an incursion of HPAI. Each scenario was parameterized in NAADSM and replicated 1000 times, generating the median number of flocks infected at the end of the simulated outbreak for each scenario. Negative binomial regression analysis was used to model significant explanatory variables of the median number of flocks infected at the end of each simulated outbreak for each of the 21 060 scenarios. The final model included the following explanatory variables: number and type initially infected flock(s), density of flocks within the county where the initially infected flock(s) was located, probability of transmission through indirect contact, subclinical spread of the infection, speed of detection and a two-way interaction between intensity of bird destruction strategy and movement restriction effectiveness to reduce transmission through direct and indirect contacts. The modelling results suggested that stamping out of the detected infected flocks, without ring culling, in combination with effective movement restrictions on direct and indirect contacts, would be the most appropriate policy for Ontario.

The relationship between smoking and knee osteoarthritis in the Osteoarthritis Initiative.

OBJECTIVE: To estimate the extent that smoking history is associated with symptoms and disease progression among individuals with radiographically confirmed knee Osteoarthritis (OA). METHOD: Both cross-sectional (baseline) and longitudinal studies employed data from the Osteoarthritis Initiative (OAI) (n = 2250 participants). Smoking history was assessed at baseline with 44% current or former smokers. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) was used to measure knee pain, stiffness, and physical function. Disease progression was measured using joint space width (JSW). We used adjusted multivariable linear models to examine the relationship between smoking status and exposure in pack years (PY) with symptoms and JSW at baseline. Changes in symptoms and JSW over time were further assessed. RESULTS: In cross-sectional analyses, compared to never-smokers high PY (≥15 PY) was associated with slightly greater pain (beta 0.36, 95% CI: 0.01-0.71) and stiffness (beta 0.20, 95% CI: 0.03-0.37); and low PY (<15 PY) was associated with better JSW (beta 0.15, 95% CI: 0.02-0.28). Current smoking was associated with greater pain (beta 0.59, 95% CI: 0.04-1.15) compared to never-smokers. These associations were not confirmed in the longitudinal study. Longitudinally, no associations were found between high or low PY or baseline smoking status with changes in symptoms (at 72 months) or JSW (at 48 months). CONCLUSION: Cross-sectional findings are likely due residual confounding. The more robust longitudinal analysis found no associations between smoking status and symptoms or JSW. Long-term smoking provides no benefits to knee OA patients while exposing them to other well-documented serious health risks.

Evaluating vaccination strategies to control foot-and-mouth disease: a model comparison study.

Simulation models can offer valuable insights into the effectiveness of different control strategies and act as important decision support tools when comparing and evaluating outbreak scenarios and control strategies. An international modelling study was performed to compare a range of vaccination strategies in the control of foot-and-mouth disease (FMD). Modelling groups from five countries (Australia, New Zealand, USA, UK, The Netherlands) participated in the study. Vaccination is increasingly being recognized as a potentially important tool in the control of FMD, although there is considerable uncertainty as to how and when it should be used. We sought to compare model outputs and assess the effectiveness of different vaccination strategies in the control of FMD. Using a standardized outbreak scenario based on data from an FMD exercise in the UK in 2010, the study showed general agreement between respective models in terms of the effectiveness of vaccination. Under the scenario assumptions, all models demonstrated that vaccination with 'stamping-out' of infected premises led to a significant reduction in predicted epidemic size and duration compared to the 'stamping-out' strategy alone. For all models there were advantages in vaccinating cattle-only rather than all species, using 3-km vaccination rings immediately around infected premises, and starting vaccination earlier in the control programme. This study has shown that certain vaccination strategies are robust even to substantial differences in model configurations. This result should increase end-user confidence in conclusions drawn from model outputs. These results can be used to support and develop effective policies for FMD control.

Simulation modelling of a hypothetical introduction of foot-and-mouth disease into Alberta.

This study describes the use of simulation modelling to evaluate the predicted benefits of an effective livestock traceability system in responding to a hypothetical introduction of foot-and-mouth disease (FMD) in to the province of Alberta, Canada, and whether or not the implementation of emergency ring vaccination in addition to a standard stamping-out (SO) strategy would lead to smaller and shorter epidemics. Three introduction scenarios were defined, with the primary case in either an intensive beef feedlot operation, an extensive cow-calf operation or in a swine operation. Disease spread was simulated using, three levels of tracing effectiveness, five types of vaccination zone, three different vaccination start times, three lengths of vaccination campaigns, two levels of culling resource and using FMD strains with two different virulence levels. Using standard SO procedures (without vaccination), improving traceability effectiveness from a level whereby only 65% of movements were traced within 5-7 days, to a capability whereby all movements were traced within 1 day, led to a reduction in the number of infected premises (IPs) between 18.7 and 64.5%, an average saving of CAN$29,000,000 in livestock compensation costs alone, and a reduction in the length of epidemics ranging from 1 to 22 days. The implementation of emergency vaccination also led to a reduction in the number of IPs and a shortening of epidemics. The effects were more pronounced when the higher virulence settings were used, with a predicted reduction in IPs of 16.6-68.7% (mean=48.6%) and epidemics shortened by up to 37 days. Multi-variable analyses showed these effects were highly significant, after accounting for the incursion location, virulence of virus and time of first detection. The results clearly demonstrated the benefits of having effective traceability systems with rapid query and reporting functionality. The results also supported the value of early vaccination as an adjunct to SO in reducing the number of IPs and shortening the length of the epidemics. The most effective vaccination strategy involved a 3 km or larger suppressive vaccination zone around all IPs, begun as soon as practicable after first detection, and which continued until the last IP was detected.

Association between tuberculosis treatment outcomes and the mobile antiretroviral therapy programme in Zambia.

SETTING: Free antiretroviral therapy (ART) services in Zambia were introduced in hospitals beginning in 2005 and in selected rural health centres (RHCs) beginning in 2007 through the mobile ART programme. OBJECTIVE: To analyse the impact of scaling up ART services on tuberculosis (TB) treatment outcomes in Mumbwa District, Zambia. DESIGN: TB patients registered at all RHCs in the district between July 2006 and September 2009 were reviewed. RHCs were divided into two groups: 'ART sites', which provided ART services after 2007, and 'non-ART sites', which did not provide such services even after 2007. A before-after comparison analysis of TB patients was conducted between the groups. RESULTS: A total of 732 patients were enrolled (median age 34.5 years; female 44.4%). The overall human immunodeficiency virus (HIV) testing rate was 72.3% and 66.7% of these patients were HIV-positive. The TB treatment success rate at the ART sites increased significantly compared to non-ART sites after the mobile ART programme was started (P < 0.01). The HIV testing acceptance rate also increased dramatically at ART sites, which facilitated intensified case finding (P = 0.02). CONCLUSION: Scaling up ART services in rural health facilities through the mobile ART programme was found to be associated with greatly improved anti-tuberculosis treatment outcomes.

The World Organisation for Animal Health and epidemiological modelling: background and objectives.

The papers in this issue of the Scientific and Technical Review (the Review) examine uses of modelling as a tool to supportthe formulation of disease control policy and applications of models for various aspects of animal disease management. Different issues in model development and several types of models are described. The experience with modelling during the 2001 foot and mouth disease outbreak in the United Kingdom underlines how models might be appropriately applied by decision-makers when preparing for and dealing with animal health emergencies. This paper outlines the involvement of the World Organisation for Animal Health (OIE) in epidemiological modelling since 2005, with emphasis on the outcome of the 2007 questionnaire survey of model usage among Member Countries, the subsequent OIE General Session resolution and the 2008 epidemiological modelling workshop at the Centers for Epidemiology and Animal Health in the United States. Many of the workshop presentations were developed into the papers that are presented in this issue of the Review.

Introduction to network analysis and its implications for animal disease modelling.

Social networks analysis (SNA) has recently been used in veterinary epidemiology to study livestock movements. A network is obtained by considering livestock holdings as nodes in a network and movements among holdings as links among nodes. Social networks analysis enables the study of the network as a whole, exploring all the relationships among pairs of farms. Highly connected livestock holdings in the network can be identified, which can help surveillance and disease prevention activities. Observed livestock movement networks in various countries have shown an important level of contact heterogeneity and clustering (topological, not necessarily geographical or spatial) and understanding the architecture of these networks has provided a better understanding of how infections may spread. The findings of SNA studies of livestock movement should be used to build and parameterise epidemiological models of infection spread in order to improve the reliability of the outputs from these models.

Foot and mouth disease model verification and 'relative validation' through a formal model comparison.

Researchers from Australia, New Zealand, Canada and the United States collaborated to validate their foot and mouth disease models--AusSpread, InterSpread Plus and the North American Animal Disease Spread Model--in an effort to build confidence in their use as decision-support tools. The final stage of this project involved using the three models to simulate a number of disease outbreak scenarios, with data from the Republic of Ireland. The scenarios included an uncontrolled epidemic, and epidemics managed by combinations of stamping out and vaccination. The predicted numbers of infected premises, the duration of each epidemic, and the size of predicted outbreak areas were compared. Relative within-model between-scenario changes resulting from different control strategies or resource constraints in different scenarios were quantified and compared. Although there were differences between the models in absolute outcomes, between-scenario comparisons within each model were similar. In all three models, early use of ring vaccination resulted in the largest drop in number of infected premises compared with the standard stamping-out regimen. This consistency implies that the assumptions made by each of the three modelling teams were appropriate, which in turn serves to increase end-user confidence in predictions made by these models.

Adapting existing models of highly contagious diseases to countries other than their country of origin.

Many countries do not have the resources to develop epidemiological models of animal diseases. As a result, it is tempting to use models developed in other countries. However, an existing model may need to be adapted in order for it to be appropriately applied in a country, region, or situation other than that for which it was originally developed. The process of adapting a model has a number of benefits for both model builders and model users. For model builders, it provides insight into the applicability of their model and potentially the opportunity to obtain data for operational validation of components of their model. For users, it is a chance to think about the infection transmission process in detail, to review the data available for modelling, and to learn the principles of epidemiological modelling. Various issues must be addressed when considering adapting a model. Most critically, the assumptions and purpose behind the model must be thoroughly understood, so that new users can determine its suitability for their situation. The process of adapting a model might simply involve changing existing model parameter values (for example, to better represent livestock demographics in a country or region), or might require more substantial (and more labour-intensive) changes to the model code and conceptual model. Adapting a model is easier if the model has a user-friendly interface and easy-to-read user documentation. In addition, models built as frameworks within which disease processes and livestock demographics and contacts are flexible are good candidates for technology transfer projects, which lead to long-term collaborations.

Using simplified models to communicate the importance of prevention, detection and preparedness before a disease outbreak.

Frontline farm workers and veterinary-policy-makers are arguably in the best positions to influence prevention, detection, and preparedness-for-control of farm animal diseases. It is important that such individuals make biologically sound decisions concerning the daily management and regulation of the health of animals. Such decisions should be based on a good understanding of key principles of disease spread and control. This paper summarises these principles, as described in previous publications, into simple models. These models may be used to communicate concepts to readers who may not have time to study more complex models. These models illustrate the relationship between the development of new disease cases (from existing cases, i.e., the reproductive ratio R) and (i) the duration of the period during which existing cases are available as infectious, (ii) contact rates, (iii) transmission rates and (iv) susceptibility. Understanding these concepts through models has great utility, facilitating better decisions for disease prevention, detection and preparedness-for-control, before an outbreak becomes unmanageable. These basic concepts apply to all animal species, including humans.

Estimating potential epidemic size following introduction of a long-incubation disease in scale-free connected networks of milking-cow movements in Ontario, Canada.

We used the movements of adult milking cows among farms enrolled in the Dairy Herd Improvement (DHI) program in Ontario to explore the size of an epidemic that might result from farm-to-farm movements of cows in the Province if a reportable long-incubation infection like tuberculosis (TB) were introduced and not detected for 1-3 years after introduction. A directed network was created for each year (2004-2006) using all pairs of individual shipments, defined as the movement of one or more cows on a single day, from a single source DHI farm to a single recipient DHI farm. A 3-year network was also developed that included all cow shipments that took place during these 3 years. The lower and upper bounds of potential maximal epidemic size were estimated using four network-analysis measures: (1) the farm out-degree, (2) the size of the largest strong and weak components, (3) the bow-tie approach, classifying farms into six different areas of a directed network and (4) the infection chain of a farm. All four of the DHI movement networks were found to be small-world, indicating that infection could spread over considerable distances by shipments that linked potentially distant clusters of farms. The networks were also scale-free, indicating most farms had relatively few connections to other farms, while there were a few highly connected farms. Characterization of the yearly networks showed that 41-47% of DHI farms were not involved in any cow shipments and were therefore not at risk of infection from this movement network; furthermore, if infection were introduced into a DHI farm that shipped animals that year, the infection would have stopped at that farm (or at least, not been passed on by shipment of adult milking cows) >50% of the time, and 75% of the time only one more DHI farm would have become infected through animal movements. Compared to the infection chain, which accounted for both the direction and the time sequence of shipments in the movement network, the other network-analysis measures provided biased estimates of potential epidemic size. The bow-tie approach provided a schematic representation of the level of risk of each farm in the network in spreading an infection, but overestimated the lower- and upper-bound measures of potential epidemic size because it did not account for the time sequence of shipments. Our infection-chain results suggest that introducing a long-incubation disease into the network of farms enrolled in the DHI program in Ontario that was not identified until 12 months after the incursion would, in a worst-case scenario, have resulted in 168 farms (representing 5% of all Ontario DHI herds) being infected as a consequence of adult cow movements among DHI farms. This estimate increased to 850 farms (26% of all DHI herds) if the infection were not identified for 36 months.

Helicobacter pylori antigenemia in an asymptomatic population of Eastern Cape Province, South Africa: public health implications.

Helicobacter pylori is a major cause of such upper gastrointestinal diseases as gastritis, peptic ulcer, and gastric cancer. The risk of infection is increased in those living in the developing world, which has been ascribed to precarious hygiene standards, crowded households, and deficient sanitation common in this part of the world. Fecal samples were collected from 356 apparently healthy subjects, consisting of 168 males and 188 females aged from 3 months to > or = 60 years (Mean = 31 years). A standardized questionnaire describing demographic characteristic including age, sex, household hygiene, socioeconomic status, and so on was applied. A sandwich-type enzyme immunoassay amplification technology (Amplified IDEIA Hp StAR, Oxoid, UK) was used to analyze the fecal samples for the detection of H. pylori antigens using monoclonal antibodies specific for H. pylori antigens. Fisher's exact test was used to assess the univariate association between H. pylori infection and the possible risk factors. Odds ratio (OR) and the corresponding 95% confidence interval (CI) were calculated to measure the strength of association using EPI INFO 3.41 package. P values of < .05 were required for significance. H. pylori antigen was detected in 309 of the 356 subjects giving an overall prevalence of 86.8%. Prevalence increased with age from 75.9% in children < 12 years age to 100% in young adults aged 25-47 years and subjects aged > or = 60 years (P < .05). H. pylori prevalence was higher in females than in males. Of 188 females who participated in the study, H. pylori antigen was detected in 172 (91.5%) versus 144 (85.7%) 168 males (P > .05). Interestingly, H. pylori antigen was detected more often (100%) in the high socioeconomic group than in those of low socioeconomic group (85.9%) (P > .05). The results of this study have revealed a high prevalence of H. pylori antigens in fecal samples of asymptomatic individuals in the Nkonkobe municipality, an indication of active infection. Socioeconomic status, contaminated water, and poor sanitation may play a role in H. pylori transmission in this population. This finding is of public health and epidemiologic significance.

Helicobacter pylori in water sources: a global environmental health concern.

Helicobacter pylori are Gram-negative micro-aerophilic motile curve rods that inhabit the gastric mucosa of the human stomach. The bacterium chronically infects billions of people worldwide and is one of the most genetically diverse of bacterial species. More than half of the world population in both developed and developing countries are infected with this organism. Infection usually occurs without overt clinical symptoms, particularly in poor communities. If untreated, the infection can last for decades without causing symptoms. In some communities, however, infection with the organism causes peptic and duodenal ulcers, gastritis, duodenitis, and gastric cancers. How H. pylori initially enters the stomach is not known, but contaminated food particles and water are suspected, with the former physically shielding it from stomach acid. Similarly, the route of transmission of this pathogen is unknown. Several reports have suggested the possibility of waterborne transmission as the organism can survive for a few days in fresh cold water, salt water, distilled water, and tap water. Knowledge of the epidemiology and mode of transmission of H. pylori is important to prevent its spread and may be useful in identifying high risk populations.

An African perspective on Helicobacter pylori: prevalence of human infection, drug resistance, and alternative approaches to treatment.

Helicobacter pylori is a Gram-negative, micro-aerophilic, motile, curved rod that inhabits the gastric mucosa of the human stomach. It chronically infects thousands of millions of people world-wide, and is one of the most genetically diverse of bacterial species. Infection with the bacterium leads to chronic gastritis, peptic ulceration, gastric cancers and gastric mucosa-associated lymphoid-tissue (MALT) lymphoma. The prevalence of infection appears to be partly determined by geographical and socio-demographic factors, being higher in Africa than elsewhere. Current treatment, based on potent combinations that each consist of a proton-pump inhibitor and two antibiotics, is successful in 80%-90% of patients. Some undesirable side-effects, poor patient compliance and drug resistance are, however, associated with significant levels of treatment failure and with contra-indications for some patients. Antibiotic resistance in H. pylori is a growing global concern that merits the urgent attention of public-health authorities. Numerous pieces of clinical evidence have revealed that eradication of the organism from a patient results in improvement of gastritis and drastically decreases the frequency of relapse of gastric and duodenal ulcers. Natural products, including medicinal plants and honey, may offer useful alternatives in the treatment of H. pylori-related infections.

A review of network analysis terminology and its application to foot-and-mouth disease modelling and policy development.

Livestock movements are important in spreading infectious diseases and many countries have developed regulations that require farmers to report livestock movements to authorities. This has led to the availability of large amounts of data for analysis and inclusion in computer simulation models developed to support policy formulation. Social network analysis has become increasingly popular to study and characterize the networks resulting from the movement of livestock from farm-to-farm and through other types of livestock operations. Network analysis is a powerful tool that allows one to study the relationships created among these operations, providing information on the role that they play in acquiring and spreading infectious diseases, information that is not readily available from more traditional livestock movement studies. Recent advances in the study of real-world complex networks are now being applied to veterinary epidemiology and infectious disease modelling and control. A review of the principles of network analysis and of the relevance of various complex network theories to infectious disease modelling and control is presented in this paper.

Autologous SCT with a dose-reduced BU and CY regimen in older patients with non-Hodgkin's lymphoma.

Autologous SCT is a potentially curative procedure for patients with relapsed lymphoma (NHL). We analyzed the outcomes of 34 patients > or =60 years old, including eight patients > or =70 years old, who received BU and CY and SCT for NHL. Patients received BU 0.8 mg/kg i.v. (n=25) or 1 mg/kg p.o. (n=9) q 6 h x 14 doses and CY 60 mg/kg i.v. q day x 2 days. The median age was 66 (range, 60-78) years. Twenty-two patients had large cell, 10 follicular and two-mantle cell lymphoma. Fifteen patients were in a second or greater CR and 19 patients were in a PR. The median days to ANC >500/microl and platelet count >50,000/microl were 10 and 13 days respectively. The 100-day transplant-related mortality was 0%. Toxicities included interstitial lung disease (n=2), seizures in a patient with CNS lymphoma (n=1), mild veno-occlusive disease (n=2), and transient atrial fibrillation (n=4). With a median follow-up of 40 months, the 2-year overall survival and PFS were 67 and 54% respectively. BU/CY is a well-tolerated conditioning regimen for older patients with NHL. Age alone should not be used as an exclusion criterion for autologous SCT.