Mycobacterium avium subspecies paratuberculosis is the causative agent of Johne's disease, a chronic enteritis in ruminants including cattle, sheep, goats, and farmed deer. Recently, this bacterium has received an increasingly wide interest because of a rapidly growing body of scientific evidence which suggests that human infection with this microorganism may be causing some, and possibly all, cases of Crohn's disease. Recent studies have shown that a high percentage of people with Crohn's disease are infected with M. avium subsp. paratuberculosis; whether the association of this bacterium and Crohn's disease is causal or coincidental is not known. Crohn's disease is a gastrointestinal disease in humans with similar histopathological findings to those observed in the paucibacillary form of Johne's disease in cattle. The search for risk factors in Crohn's disease has been frustrating. However, epidemiologists have gathered enough information that points to an association between M. avium subsp. paratuberculosis and Crohn's disease. This paper reviews epidemiological models of disease causation, the major philosophical doctrines about causation, the established epidemiological criteria for causation, and the currently known epidemiological evidence of M. avium subsp. paratuberculosis as a possible cause of Crohn's disease.

People living in endemic areas acquire Lyme disease from the bite of an infected tick. This infection, when diagnosed and treated early in its course, usually responds well to antibiotic therapy. A minority of patients develops more serious disease, particularly after a delay in diagnosis or therapy, and sometimes chronic neurological, cardiac, or rheumatological manifestations. In 1998, the FDA approved a new recombinant Lyme vaccine, LYMErix™, which reduced new infections in vaccinated adults by nearly 80%. Just 3 years later, the manufacturer voluntarily withdrew its product from the market amidst media coverage, fears of vaccine side-effects, and declining sales. This paper reviews these events in detail and focuses on the public communication of risks and benefits of the Lyme vaccine and important lessons learned.

This review examines the current situation of bovine tuberculosis (bTB) in southern African savannah systems, and uses theory on multi-species host–pathogen systems to suggest possible options for future research and management. In southern Africa, the buffalo (Syncerus caffer) and the Kafue lechwe [Marsh antelope] (Kobus leche) have been found to be maintenance hosts for this disease, but the importance of other host species is becoming apparent. The role of other host species in the maintenance and spread of the disease varies, depending on the spatial distribution and resource utilization patterns of the species, disease susceptibility, transmission modes and the ecology of both host(s) and vector(s). Future research needs to identify the pathogenicity of bTB in each of the host species, and the mechanisms and rates of inter- and intra-specific transmission among different species, in order to develop multi-host models to understand the development and spread of the disease.

The purpose of this study was to assess and describe the current spectrum of emerging zoonoses between 2000 and 2006 in European countries. A computerized search of the Medline database from January 1966 to August 2006 for all zoonotic agents in European countries was performed using specific criteria for emergence. Fifteen pathogens were identified as emerging in Europe from 2000 to August 2006: Rickettsiae spp., Anaplasma phagocytophilum, Borrelia burgdorferi, Bartonella spp., Francisella tularensis, Crimean Congo Haemorrhagic Fever Virus, Hantavirus, Toscana virus, Tick-borne encephalitis virus group, West Nile virus, Sindbis virus, Highly Pathogenic Avian influenza, variant Creutzfeldt–Jakob disease, Trichinella spp., and Echinococus multilocularis. Main risk factors included climatic variations, certain human activities as well as movements of animals, people or goods. Multi-disciplinary preventive strategies addressing these pathogens are of public health importance. Uniform harmonized case definitions should be introduced throughout Europe as true prevalence and incidence estimates are otherwise impossible.

Public health authorities should be vigilant to the potential for outbreaks deliberately caused by biological agents (bioterrorism). Such events require a rapid response and incorporation of non-traditional partners for disease investigation and outbreak control. The astute application of infectious disease epidemiological principles can promote an enhanced index of suspicion for such events. We discuss epidemiological indicators that should be considered during outbreak investigations, and also examine their application during bioterrorism incidents, an accidental release of an agent, outbreaks of infections that were alleged to have been deliberately initiated, and a model scenario. The Grunow & Finke epidemiological assessment tool is used to examine these historical events and the model scenario. The results received from this analysis, coupled with an understanding of epidemiological clues to unnatural events, and knowledge of how to manage such events, can aid in the improved response and resolution of epidemics.

The efficacy of the conventional bacille Calmette-Guérin (BCG) vaccine is often questioned because of conflicting trial results [1]. In this context, a new BCG vaccine developed by Grode et al. [2] has been seen as a favourable development in tuberculosis (TB) control [3]. BCG vaccine development is a challenge for many reasons, not least of which is the complex immunology of mycobacterial infections. The pathogenesis of TB, and prevention of TB by BCG, is predominantly a function of cell-mediated immunity. Mycobacterium tuberculosis (MTB) and BCG are phagocytosed, but remain viable for some time within the phagosome. There, BCG antigens must be presented to major histocompatibility complex (MHC) class II molecules to activate CD4+ cells, and to MHC class I molecules to activate CD8+ cells [3]. However, both MTB and BCG fail to activate CD8+ cells sufficiently. The relative failure of activation of CD8+ cells is thought to be related to the enzyme urease, which keeps the intracellular pH high and thus inhibits presentation of antigens to T cells which would otherwise activate the CD8+ response. Grode et al. [2] have engineered a BCG strain which overcomes this problem and allows release of antigen into the cell and thereby stimulates a CD8+ cell response in addition to the CD4 response seen with conventional BCG. They did this first by engineering a strain of BCG which secretes listeriolysin (Hly), an enzyme from Listeria monocytogenes which perforates cell membranes.

We examined different patient outcomes following diagnosis of tuberculosis (TB). Incident cases were reported to the enhanced surveillance system in the East of England, between 2000 and 2003. For the 575 cases reported in 2001 and 2002, outcomes were assessed 1 year after initiating treatment. The crude clinical incidence rate of TB was 6·0 cases/100 000 person-years (pyr) [95% confidence interval (CI) 5·7–6·4], highest in the 25–29 years age group (14·9, 95% CI 12·9–17·1 cases/100 000 pyr) and among Black Africans (328·6, 95% CI 286·9–374·6 cases/100 000 pyr). Patients born abroad were 2·35 (95% CI 1·03–5·32) times more likely to be lost to follow-up than those born in the United Kingdom. Age at diagnosis (OR 1·05, 95% CI 1·04–1·07) and pulmonary disease (OR 2·73, 95% CI 1·21–6·15) were independently associated with mortality. Elderly patients and those with pulmonary TB appear to have worse outcomes despite treatment. Foreign-born patients may need closer follow-up to ensure favourable outcomes.

In randomized trials, the treatment assignment mechanism is independent of the outcome of interest and other covariates thought to be relevant in determining this outcome. It also allows, on average, for a balanced distribution of these covariates in the vaccine and placebo groups. Randomization, however, does not guarantee that the estimated effect is an unbiased estimate of the biological effect of interest. We show how exposure to infection can be a confounder even in randomized vaccine field trials. Based on a simple model of the biological efficacy of interest, we extend the arguments on comparability and collapsibility to examine the limits of randomization to control for unmeasured covariates. Estimates from randomized, placebo-controlled Phase III vaccine field trials that differ in baseline transmission are not comparable unless explicit control for baseline transmission is taken into account.

Relevance of epidemiological models depends on assumptions on the population structure and dynamics, on the biology of the host–parasite interaction, and on mathematical modelling. In this paper we reviewed published models of the bovine viral diarrhoea virus (BVDV) spread within a herd. Modelling options and assumptions on herd dynamics and BVDV transmission were discussed. A cattle herd is a population with a controlled size. Animals are separated into subgroups according to their age or their physiological status inducing heterogeneity of horizontal transmission. Complexity of models results from: (1) horizontal and vertical virus transmission, (2) birth of persistently infected animals, (3) excretion by transiently and persistently infected animals. Areas where there was a lack of knowledge were identified. Assumptions on the force of infection used to model the horizontal virus transmission were presented and discussed. We proposed possible ways of improving models (e.g. force of infection, validation) and essential model features for further BVDV models.

We observed an outbreak of necrotizing fasciitis associated with Streptococcus agalactiae infection in a group of juvenile saltwater crocodiles (Crocodylus porosus). We undertook screening of crocodiles and the environment to clarify the source of the outbreak and evaluated the isolates cultured from post-mortem specimens with molecular methods to assess clonality and the presence of known group B streptococcal virulence determinants. The isolates were indistinguishable by pulsed-field gel electrophoresis. They were a typical serotype Ia strain with the Cα-like protein gene, epsilon (or alp1), the mobile genetic elements IS381 ISSag1 and ISSag2, and belonged to multi-locus sequence type (ST) 23. All of these characteristics suggest they were probably of human origin. We review the medical and veterinary literature relating to S. agalactiae necrotizing fasciitis, epidemiology and virulence determinants.

Between 1992 and 2004, a total of 49 819 confirmed hepatitis C infections have been reported to the Health Protection Agency (HPA) by laboratories in England and Wales; the annual number of reports increased from 241 in 1991 to 8149 in 2004. Most reports with a known risk factor were in injecting drug users (87%, 12 438/14 221), but 71% (35 598/49 819) of the total had no reported identified risk. The age-sex distribution of the latter cases was similar to that in injecting drug users. Using names to assign ethnicity, individuals with South Asian names had an older age distribution and a different risk factor profile from non-South Asians. Using published age-specific prevalence data from 1996, it was estimated that around 281 764 cases of hepatitis C infection exist in England and Wales, and that only 17% of these cases have been reported to the HPA. Surveillance reports continue to provide important information regarding trends in hepatitis C infection in specific risk groups.

The ongoing worldwide spread of the H5N1 influenza virus in birds has increased concerns of a new human influenza pandemic and a number of surveillance initiatives are planned, or are in place, to monitor the impact of a pandemic in near real-time. Using epidemiological data collected during the early stages of an outbreak, we show how the timing of the maximum prevalence of the pandemic wave, along with its amplitude and duration, might be predicted by fitting a mass-action epidemic model to the surveillance data by standard regression analysis. This method is validated by applying the model to routine data collected in the United Kingdom during the different waves of the previous three pandemics. The success of the method in forecasting historical prevalence suggests that such outbreaks conform reasonably well to the theoretical model, a factor which may be exploited in a future pandemic to update ongoing planning and response.

In Argentina, bovine leukaemia virus (BLV) infection is common in dairy herds. The country currently has a National Voluntary Control Programme but relatively few farms have enrolled. However, there is increased interest from authorities and farmers to implement regional compulsory programmes but there is scarce quantitative information of the transmission of BLV in cattle herds. This information is a prerequisite to develop effective BLV control strategies. Mathematical modelling offers ways of integrating population-level knowledge and epidemiological data to predict the outcomes of intervention scenarios. The purpose of the current paper is to gain understanding about the dynamics of the transmission of BLV in dairy herds from Argentina by simulation and to compare various BLV transmission models and select the one that is most appropriate. The hypothetical herd is conceptually described in terms of BLV status as a population of individuals that are protected by maternal antibodies (M), that are susceptible (S), that are in the latent period (E) or that are infectious (I). BLV is spread by horizontal and vertical transmission. We used an age-structured population model and within-herd transmission was simulated by Monte Carlo techniques. The next-generation approach has been used for the systematic computation of the basic reproduction ratio (R0). Parameter values for disease transmission were derived from previously published data; rates of entry, exit or transition between age groups were calculated based on our previous study, observational data, expert opinions and literature. With these parameter values the probability of a minor outbreak was estimated to be 10%, the probability of extinction was estimated as <0·001% and the expected time to extinction as more than 80 years. The probability of a minor outbreak and changes in prevalence were different when the index case was an adult cow compared to introduction by a heifer. Prediction of prevalences from MSI models fit the data satisfactorily. R0 was estimated as 9·5. The sensitivity analysis on R0 showed that all measures directed to reduce the transmission rate are potentially effective given operational control measures. An important prediction of these models is that, even in a relatively small, closed dairy herd, the time-scale for a BLV outbreak may be as long as several years and within-herd control of BLV requires intensive efforts.

Francisella tularensis was identified as the cause of a die-off which occurred among a colony of semi-free-living common marmosets (Callithrix jacchus). During the outbreak 5 out of 62 animals died of tularaemia in a research facility located in the district of Goettingen, Germany. All animals had been born at the facility suggesting an endemic infection. A total of five culture isolates were recovered and characterized as F. tularensis holarctica, biovar I. These cultures represent the first isolates obtained in the Federal Republic of Germany for more than 45 years. The outbreak area shows several geographical and ecological characteristics known to favour long-term presence of F. tularensis. Persistence of the pathogen in the remote region along the former German–German border, continuous re-introduction from eastern European countries after destruction of the ‘Iron curtain’ or introduction through migrating birds are testable hypotheses which could explain the emergence of tularaemia in this particular region.

We characterized eleven H9N2 influenza A viruses isolated from chicken products imported from China. Genetically they were classified into six distinct genotypes, including five already known genotypes and one novel genotype. This suggested that such multiple genotypes of the H9N2 virus have possibly already become widespread and endemic in China. Two isolates have amino-acid substitutions that confer resistance to amantadine in the M2 region, and this supported the evidence that this mutation might be a result of the wide application of amantadine for avian influenza treatment in China. These findings emphasize the importance of surveillance for avian influenza virus in this region, and of quarantining imported chicken products as potential sources for the introduction of influenza virus.

The aim of the study was to determine whether rates of hepatitis A infection are higher in people of South Asian origin compared to the general population, to look for evidence of spread to the general population, and to identify ways to improve preventive strategies. Routine laboratory reports of hepatitis A infection in England and Wales in 1992–2004 were analysed. Study participants were patients with confirmed hepatitis A infection reported to the Health Protection Agency by the diagnosing laboratory. Nam Pehchan software was used to identify patients of South Asian ethnicity. Main outcome measures were comparison of incidence of hepatitis A in South Asian and non-South Asian groups, by age and region. Rates of infection were significantly higher in the South Asian group compared to the non-South Asian group (rate ratio 2·68, 95% confidence interval 2·07–3·47). Patients in the South Asian group had a younger age distribution. Travel was an important risk factor with 85% of those of South Asian origin acquiring their infection abroad, most frequently in the Indian subcontinent, compared to less than one third of those in other groups. Health-care professionals should ensure that all travellers to high-risk countries are protected by hepatitis A vaccination. Targeted information campaigns may be indicated in regions of the United Kingdom for people in South Asian minority ethnic groups.