SciCombinator

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Concept: Mycobacterium bovis

16

Bovine tuberculosis (BTB) is a multi-species infection that commonly affects cattle and badgers in Great Britain. Despite years of study, the impact of badgers on BTB incidence in cattle is poorly understood. Using a two-host transmission model of BTB in cattle and badgers, we find that published data and parameter estimates are most consistent with a system at the threshold of control. The most consistent explanation for data obtained from cattle and badger populations includes within-host reproduction numbers close to 1 and between-host reproduction numbers of approximately 0.05. In terms of controlling infection in cattle, reducing cattle-to-cattle transmission is essential. In some regions, even large reductions in badger prevalence can have a modest impact on cattle infection and a multi-stranded approach is necessary that also targets badger-to-cattle transmission directly. The new perspective highlighted by this two-host approach provides insight into the control of BTB in Great Britain.

Concepts: Disease, Tuberculosis, Cattle, Mycobacterium bovis, Ireland

12

Bovine tuberculosis is endemic in cattle herds in Great Britain, with a substantial economic impact. A reservoir of Mycobacterium bovis within the Eurasian badger (Meles meles) population is thought to have hindered disease control. Cattle herd incidents, termed breakdowns, that are either ‘prolonged’ (lasting ≥240 days) or ‘recurrent’ (with another breakdown within a specified time period) may be important foci for onward spread of infection. They drain veterinary resources and can be demoralising for farmers. Randomised Badger Culling Trial (RBCT) data were re-analysed to examine the effects of two culling strategies on breakdown prolongation and recurrence, during and after culling, using a Bayesian hierarchical model. Separate effect estimates were obtained for the ‘core’ trial areas (where culling occurred) and the ‘buffer’ zones (up to 2 km outside of the core areas). For breakdowns that started during the culling period, ‘reactive’ (localised) culling was associated with marginally increased odds of prolongation, with an odds ratio (OR) of 1.7 (95% credible interval [CI] 1.1-2.4) within the core areas. This effect was not present after the culling ceased. There was no notable effect of ‘proactive’ culling on prolongation. In contrast, reactive culling had no effect on breakdown recurrence, though there was evidence of a reduced risk of recurrence in proactive core areas during the culling period (ORs and 95% CIs: 0.82 (0.64-1.0) and 0.69 (0.54-0.86) for 24- and 36-month recurrence respectively). Again these effects were not present after the culling ceased. There seemed to be no effect of culling on breakdown prolongation or recurrence in the buffer zones. These results suggest that the RBCT badger culling strategies are unlikely to reduce either the prolongation or recurrence of breakdowns in the long term, and that reactive strategies (such as employed during the RBCT) are, if anything, likely to impact detrimentally on breakdown persistence.

Concepts: Tuberculosis, Mycobacterium, Cattle, Mycobacterium bovis, Badger, European Badger, Meles, Badgers

10

Bovine tuberculosis (TB) is one of the most complex, persistent and controversial problems facing the British cattle industry, costing the country an estimated £100 million per year. The low sensitivity of the standard diagnostic test leads to considerable ambiguity in determining the main transmission routes of infection, which exacerbates the continuing scientific debate. In turn this uncertainty fuels the fierce public and political disputes on the necessity of controlling badgers to limit the spread of infection. Here we present a dynamic stochastic spatial model for bovine TB in Great Britain that combines within-farm and between-farm transmission. At the farm scale the model incorporates stochastic transmission of infection, maintenance of infection in the environment and a testing protocol that mimics historical government policy. Between-farm transmission has a short-range environmental component and is explicitly driven by movements of individual cattle between farms, as recorded in the Cattle Tracing System. The resultant model replicates the observed annual increase of infection over time as well as the spread of infection into new areas. Given that our model is mechanistic, it can ascribe transmission pathways to each new case; the majority of newly detected cases involve several transmission routes with moving infected cattle, reinfection from an environmental reservoir and poor sensitivity of the diagnostic test all having substantive roles. This underpins our findings on the implications of control measures. Very few of the control options tested have the potential to reverse the observed annual increase, with only intensive strategies such as whole-herd culling or additional national testing proving highly effective, whereas controls focused on a single transmission route are unlikely to be highly effective.

Concepts: Scientific method, Mathematics, Tuberculosis, Mycobacterium, Philosophy of science, Cattle, Mycobacterium bovis, Bacillus Calmette-Guérin

10

We aimed to estimate the global occurrence of zoonotic tuberculosis (TB) caused by Mycobacterium bovis or M. caprae infections in humans by performing a multilingual, systematic review and analysis of relevant scientific literature of the last 2 decades. Although information from many parts of the world was not available, data from 61 countries suggested a low global disease incidence. In regions outside Africa included in this study, overall median proportions of zoonotic TB of ≤1.4% in connection with overall TB incidence rates ≤71/100,000 population/year suggested low incidence rates. For countries of Africa included in the study, we multiplied the observed median proportion of zoonotic TB cases of 2.8% with the continental average overall TB incidence rate of 264/100,000 population/year, which resulted in a crude estimate of 7 zoonotic TB cases/100,000 population/year. These generally low incidence rates notwithstanding, available data indicated substantial consequences of this disease for some population groups and settings.

Concepts: Epidemiology, Incidence, Tuberculosis, Mycobacterium, Prevalence, Mycobacterium bovis

9

Bovine tuberculosis (BTB) is an endemic zoonosis in Morocco caused by Mycobacterium bovis, which infects many domestic animals and is transmitted to humans through consumption of raw milk or from contact with infected animals. The prevalence of BTB in Moroccan cattle is estimated at 18%, and 33% at the individual and the herd level respectively, but the human M. bovis burden needs further clarification. The current control strategy based on test and slaughter should be improved through local context adaptation taking into account a suitable compensation in order to reduce BTB prevalence in Morocco and decrease the disease burden in humans and animals. We established a simple compartmental deterministic mathematical model for BTB transmission in cattle and humans to provide a general understanding of BTB, in particular regarding transmission to humans. Differential equations were used to model the different pathways between the compartments for cattle and humans. Scenarios of test and slaughter were simulated to determine the effects of varying the proportion of tested animals (p) on the time to elimination of BTB (individual animal prevalence of less than one in a thousand) in cattle and humans. The time to freedom from disease ranged from 75 years for p = 20% to 12 years for p = 100%. For p > 60% the time to elimination was less than 20 years. The cumulated cost was largely stable: for p values higher than 40%, cost ranged from 1.47 to 1.60 billion euros with a time frame of 12 to 32 years to reach freedom from disease. The model simulations also suggest that using a 2mm cut off instead of a 4mm cut off in the Single Intradermal Comparative Cervical Tuberculin skin test (SICCT) would result in cheaper and quicker elimination programs. This analysis informs Moroccan bovine tuberculosis control policy regarding time frame, range of cost and levels of intervention. However, further research is needed to clarify the national human-bovine tuberculosis ratio in Morocco.

Concepts: Tuberculosis, Mycobacterium, Cattle, Mycobacterium bovis, Bacillus Calmette-Guérin, Tuberculosis treatment, Zoonosis, Pyrazinamide

9

Where wildlife disease requires management, culling is frequently considered but not always effective. In the British Isles, control of cattle tuberculosis (TB) is hindered by infection in wild badger (Meles meles) populations. Large-scale badger culling can reduce the incidence of confirmed cattle TB, but these benefits are undermined by culling-induced changes in badger behavior (termed perturbation), which can increase transmission among badgers and from badgers to cattle. Test-vaccinate/remove (TVR) is a novel approach that entails testing individual badgers for infection, vaccinating test-negative animals, and killing test-positive animals. Imperfect capture success, diagnostic sensitivity, and vaccine effectiveness mean that TVR would be expected to leave some infected and some susceptible badgers in the population. Existing simulation models predict that TVR could reduce cattle TB if such small-scale culling causes no perturbation, but could increase cattle TB if considerable perturbation occurs. Using data from a long-term study, we show that past small-scale culling was significantly associated with four metrics of perturbation in badgers: expanded ranging, more frequent immigration, lower genetic relatedness, and elevated prevalence of Mycobacterium bovis, the causative agent of TB. Though we could not reject the hypothesis that culling up to three badgers per social group might avoid perturbation, we also could not reject the hypothesis that killing a single badger prompted detectable perturbation. When considered alongside existing model predictions, our findings suggest that implementation of TVR, scheduled for 2014, risks exacerbating the TB problem rather than controlling it. Ongoing illegal badger culling is likewise expected to increase cattle TB risks.

Concepts: Vaccine, Tuberculosis, Mycobacterium, Mycobacterium bovis, British Isles, Badger, European Badger, Meles

7

Bovine tuberculosis is a zoonotic disease with largely unknown impact in Africa, with risk factors such as HIV and direct contact with animals or consumption of Mycobacterium bovis infected animal products. In order to understand and quantify this risk and design intervention strategies, good epidemiological studies are needed. Such studies can include molecular typing of M. bovis isolates. The aim of this study was to apply these tools to provide novel information concerning the distribution of bovine tuberculosis in cattle in Mozambique and thereby provide relevant information to guide policy development and strategies to contain the disease in livestock, and reduce the risk associated with transmission to humans. A collection of 178 M. bovis isolates was obtained from cattle in Mozambique. Using spoligotyping and regions of difference analysis, we classified the isolates into clonal complexes, thus reporting the first characterisation of M. bovis strains in this region. Data from MIRU-VNTR typing was used to compare isolates from a number of African countries, revealing a deeply geographically structured diversity of M. bovis. Eastern Africa appears to show high diversity, suggesting deep evolution in that region. The diversity of M. bovis in Africa does not seem to be a function of recent importation of animals, but is probably maintained within each particular region by constant reinfection from reservoir animals. Understanding the transmission routes of M. bovis in Mozambique and elsewhere is essential in order to focus public health and veterinary resources to contain bovine tuberculosis.

Concepts: AIDS, Epidemiology, Africa, Tuberculosis, Mycobacterium, Cattle, Mycobacterium bovis, Zoonosis

7

The Mycobacterium tuberculosis complex (MTBC) is the collective term given to the group of bacteria that cause tuberculosis (TB) in mammals. It has been reported that M. tuberculosis H37Rv, a standard reference MTBC strain, is attenuated in cattle compared to Mycobacterium bovis. However, as M. tuberculosis H37Rv was isolated in the early 1930s, and genetic variants are known to exist, we sought to revisit this question of attenuation of M. tuberculosis for cattle by performing a bovine experimental infection with a recent M. tuberculosis isolate. Here we report infection of cattle using M. bovis AF2122/97, M. tuberculosis H37Rv, and M. tuberculosis BTB1558, the latter isolated in 2008 during a TB surveillance project in Ethiopian cattle. We show that both M. tuberculosis strains caused reduced gross pathology and histopathology in cattle compared to M. bovis. Using M. tuberculosis H37Rv and M. bovis AF2122/97 as the extremes in terms of infection outcome, we used RNA-Seq analysis to explore differences in the peripheral response to infection as a route to identify biomarkers of progressive disease in contrast to a more quiescent, latent infection. Our work shows the attenuation of M. tuberculosis strains for cattle, and emphasizes the potential of the bovine model as a ‘One Health’ approach to inform human TB biomarker development and post-exposure vaccine development.

Concepts: Infectious disease, Microbiology, Vaccine, Tuberculosis, Mycobacterium, Mycobacterium tuberculosis, Cattle, Mycobacterium bovis

7

Mycobacterium bovis, one of several mycobacteria of the M. tuberculosis complex, is a global zoonotic pathogen that primarily infects cattle. Humans become infected by consuming unpasteurized dairy products from infected cows (1,2); possible person-to-person airborne transmission has also been reported (3). In April 2014, a man in Nebraska who was born in Mexico was determined to have extensive pulmonary tuberculosis (TB) caused by M. bovis after experiencing approximately 3 months of cough and fever. Four months later, a U.S.-born Hispanic girl from a nearby town who had been ill for 4-5 months was also determined to have pulmonary TB caused by M. bovis. The only social connection between the two patients was attendance at the same church, and no common dietary exposure was identified. Both patients had pulmonary cavities on radiography and acid-fast bacilli (AFB) on sputum-smear microscopy, indicators of being contagious (4). Whole-genome sequencing results of the isolates were nearly indistinguishable. Initial examination of 181 contacts determined that 39 (22%) had latent infection: 10 (42%) of 24 who had close exposure to either patient, 28 (28%) of 100 who were exposed to one or both patients in church, and one (2%) of 57 exposed to the second patient at a school. Latent infection was diagnosed in six contacts on follow-up examination, 2 months after an initial negative test result (4), for an overall latent infection rate of 25%. No infected contacts recalled consuming unpasteurized dairy products, and none had active TB disease at the initial or secondary examination. Persons who have M. bovis TB should be asked about consumption of unpasteurized dairy products (2), and contact investigations should follow the same guidance as for M. tuberculosis TB (4).

Concepts: Infectious disease, Microbiology, Tuberculosis, Mycobacterium, Mycobacterium tuberculosis, Cattle, Mycobacterium bovis, Acid fast bacilli

6

Bovine tuberculosis (bTB), caused by Mycobacterium bovis, is an important livestock disease raising public health and economic concerns around the world. In New Zealand, a number of wildlife species are implicated in the spread and persistence of bTB in cattle populations, most notably the brushtail possum (Trichosurus vulpecula). Whole Genome Sequenced (WGS) M. bovis isolates sourced from infected cattle and wildlife across New Zealand were analysed. Bayesian phylogenetic analyses were conducted to estimate the substitution rate of the sampled population and investigate the role of wildlife. In addition, the utility of WGS was examined with a view to these methods being incorporated into routine bTB surveillance.

Concepts: Molecular biology, Tuberculosis, Mycobacterium, Cattle, Mycobacterium bovis, Phalangeridae, Common Brushtail Possum, Possum