Risk factors and true prevalence of bovine tuberculosis in Bangladesh.

Bovine tuberculosis (bTb) is endemic in Bangladesh but the true prevalence has not yet been reported. Our objectives for this study were to determine the true prevalence and identify risk factors for bTb at the animal- and herd-level in Bangladesh. A total of 510 cows were randomly selected during January 2018 to December 2018. Caudal fold (CFT) and comparative cervical tuberculin tests (CCT) were serially interpreted. Animal- and herd-level risk factor data were collected using a pre-tested questionnaire. The hierarchical true prevalence of bTb was estimated within a Bayesian framework. The herd- and animal-level risk factors were identified using mixed effects logistic regression. The apparent prevalence of bTb was 20.6% [95% Confidence Interval (CI): 17.3; 24.3] based on CFT. The animal-level true prevalence of bTb was 21.9 (13.0; 32.4). The herd-level true prevalence in different regions varied from 41.9% to 88.8%. The region-level true prevalence was 49.9 (13.8; 91.2). There is a 100% certainty that herds from Bhaluka and Mymensingh Sadar upazilas are not free from bTb. The odds of bTb were 3.9 times (1.2; 12.6) higher in herds having more than four cows than those with ≤ 4 cows. On the other hand, the risk of bTb was 3.3 times higher (1.0; 10.5) in non-grazing cows than grazing cows. Crossbred cows were 2.9 times (1.5; 5.9) more likely to be infected with bTb than indigenous cows. The risk of bTb in animals with cough was 2.3 times (1.2; 4.3) higher than those without cough. Crossbred, non-grazing cows with cough should be targeted for bTb surveillance. Herds of the Mymensingh, Sadar and Bhaluka regions should be emphasized for bTb control programs. Estimation of Bayesian hierarchical true prevalence facilitates identification of areas with higher prevalence and can be used to indicate regions that where true prevalence exceeds a pre-specified critical threshold.

The C3HeB/FeJ mouse model recapitulates the hallmark of bovine tuberculosis lung lesions following Mycobacterium bovis aerogenous infection.

Achieving the control of bovine tuberculosis (bTB) would require the discovery of an efficient combined immunodiagnostic and vaccine strategy. Since in vivo experiments on cattle are not ethically and economically acceptable there is a need for a cost-effective animal model capable of reproducing, as closely as possible, the physiopathology of bTB to (i) better characterize the cellular and molecular features of bTB immunopathogenesis and (ii) screen preclinical vaccine candidates. To develop such a model, we focused on the C3HeB/FeJ Kramnik's mouse forming hypoxic, encapsulated granulomas with a caseous necrotic center following Mycobacterium tuberculosis infection. Our work represents the first investigation on C3HeB/FeJ interaction with M. bovis, the main agent of bTB. Detailed histopathological analysis of C3HeB/FeJ lung lesions development following aerogenous M. bovis infection unraveled a bimodal evolution of the pathology. The C3HeB/FeJ recapitulated all the hallmarks of classical bovine lung granulomas but also developed, to some extend, lethal necrotic large lesions characterized by high mycobacterial and neutrophil load, and an inefficient collagen-driven lesion encapsulation. Interestingly these rapidly invasive pneumonia lesions, occurring in a constant percentage of the mice, shared all features with some exacerbated lung lesions that we and others have observed in lungs of cattle naturally or experimentally infected with M. bovis. Together, our findings demonstrate the relevance of the C3HeB/FeJ mouse as a comprehensive model to study bTB immunopathology that could be used for further vaccine therapies in the future.

Inhibition of TLR8 mediated signaling promotes BCG induced apoptosis in THP-1 cells.

Apoptosis was considered as one of the important host defense mechanisms against mycobacteria infection. In macrophage, the main target cell of Mycobacterium tuberculosis, apoptosis after infection could help kill the bacillus inside and process the antigens for further presentation and proper immune response. Here, we identified a role of TLR8 during the apoptosis induced by Bacillus Calmette Guérin (BCG) infection in THP-1 cells. Knockdown TLR8 further increased the apoptosis induced by BCG infection, and this enhanced apoptosis was caspase-dependent. During this process, Erk1/2, JNK and NFκB pathways were negatively affected and contributed to the enhanced apoptosis.

Evaluation of the efficiency of nested q-PCR in the detection of Mycobacterium tuberculosis complex directly from tuberculosis-suspected lesions in post-mortem macroscopic inspections of bovine carcasses slaughtered in the state of Mato Grosso, Brazil.

Bovine tuberculosis (BTB) is a zoonotic disease caused by Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex (MTC). The quick and specific detection of this species is of extreme importance, since BTB may cause economic impacts, in addition to presenting imminent risks to human health. In the present study a nested real-time PCR test (nested q-PCR) was used in post-mortem evaluations to assess cattle carcasses with BTB-suspected lesions. A total of 41,193 cattle slaughtered in slaughterhouses located in the state of Mato Grosso, were examined. Of the examined animals, 198 (0.48%) showed BTB-suspected lesions. M. bovis was isolated in 1.5% (3/198) of the samples. Multiplex-PCR detected MTC in 7% (14/198) of the samples. The nested q-PCR test detected MTC in 28% (56/198) of the BTB-suspected lesions, demonstrating higher efficiency when compared to the multiplex-PCR and conventional microbiology. Nested q-PCR can therefore be used as a complementary test in the national program for control and eradication of bovine tuberculosis.

Milk yield and reproductive performance of Holstein cows testing positive for bovine tuberculosis.

The objective of this study was to determine if high milk-yielding Holstein cows testing positive for bovine tuberculosis (bTB) are affected in their reproductive performance and milk yield. For this purpose, 1044 healthy cows and 105 bTB reactor cows were used. Tuberculosis reactor cows were from four large commercial dairy operations from the same region which were transferred from their barns to an isolated dairy facility. Cows free from this disease were placed in the same barn as the bTB reactor cows but in an isolated division and served as control animals. The analysis of variance with a general linear model for binary data showed that the reproductive performance of bTB reactors was impaired; overall pregnancy per artificial insemination differed (P < 0.05) between bTB reactor and non-reactor cows (16.9 vs. 20.7%). Cows that were TB reactors required 4.7 ± 2.9 services per pregnancy compared with 4.3 ± 2.8 for control cows (P > 0.05). The intervals between calving and conception were similar between bTB reactors (154 ± 78 days) and control animals (150 ± 80 days). Control cows tended (P = 0.08) to produce more milk than bTB reactors over a 305-day lactation (10,684 ± 1720 vs. 10,345 ± 1736; mean ± SD). Serum metabolites indicative of nutritional stress did not differ between bTB reactor and non-reactor cows. It was concluded that both reproductive performance and milk yield decreased marginally in bTB reactor cows, which explains the reluctance of milk producers to get rid of these animals.

Asymptomatic cattle naturally infected with Mycobacterium bovis present exacerbated tissue pathology and bacterial dissemination.

Rational discovery of novel immunodiagnostic and vaccine candidate antigens to control bovine tuberculosis (bTB) requires knowledge of disease immunopathogenesis. However, there remains a paucity of information on the Mycobacterium bovis-host immune interactions during the natural infection. Analysis of 247 naturally PPD+ M. bovis-infected cattle revealed that 92% (n = 228) of these animals were found to display no clinical signs, but presented severe as well as disseminated bTB-lesions at post-mortem examination. Moreover, dissemination of bTB-lesions positively correlated with both pathology severity score (Spearman r = 0.48; p<0.0001) and viable tissue bacterial loads (Spearman r = 0.58; p = 0.0001). Additionally, granuloma encapsulation negatively correlated with M. bovis growth as well as pathology severity, suggesting that encapsulation is an effective mechanism to control bacterial proliferation during natural infection. Moreover, multinucleated giant cell numbers were found to negatively correlate with bacterial counts (Spearman r = 0.25; p = 0.03) in lung granulomas. In contrast, neutrophil numbers in the granuloma were associated with increased M. bovis proliferation (Spearman r = 0.27; p = 0.021). Together, our findings suggest that encapsulation and multinucleated giant cells control M. bovis viability, whereas neutrophils may serve as a cellular biomarker of bacterial proliferation during natural infection. These data integrate host granuloma responses with mycobacterial dissemination and could provide useful immunopathological-based biomarkers of disease severity in natural infection with M. bovis, an important cattle pathogen.

Bovine tuberculosis and udder health in Irish dairy herds.

The association between bovine tuberculosis (TB) infection status based on results from the single intradermal comparative tuberculin test (SICTT) and milk production has been described in dairy cows in TB-infected herds in Ireland. The biological basis was uncertain, but could be related to increased TB susceptibility among lower producing dairy cows. In this study, the relationship between somatic cell count (as an objective measure of udder health) and SICTT reactivity (as a proxy for TB infection status) was investigated. Somatic cell counts of TB infected cows, both during and prior to the lactation of diagnosis of TB infection, were examined and compared to non-infected cows. All Irish dairy herds restricted from trading between June 2004 and May 2005 as a result of two or more TB reactors (test positive) to the SICTT were considered for study. Data were collected on 4340 cows from 419 herds. Previous lactation data for the cows were taken into consideration and all lactations on a cow were analysed together with the years of lactations. There was an inherent hierarchical structure in the data, with lactations nested within cows and cows within herds and so a linear mixed model with two random effects was used to describe the data. Milk production (305-day milk yield) was also included in the model as a fixed effect. The results of the study showed that for all lactations and years under investigation, somatic cell counts for SICTT reactor cows when compared to the non-reactor cows were not significantly different. In this study population, TB infection status was not associated with udder health.

Bovine tuberculosis and milk production in infected dairy herds in Ireland.

This study describes the relationship between bovine tuberculosis (TB) and milk yield in TB-infected dairy herds in Ireland. The study had two objectives: to determine whether cows detected as TB reactors (and thus subject to immediate slaughter) were likely to be the higher milk-producing cows, and to determine whether subclinical TB infection was associated with reduced milk production at or around the time of disclosure (detection). All Irish dairy herds restricted from trading between the 1(st) June 2004 and the 31(st) May 2005 as a result of two or more TB reactors by the Single Intradermal Comparative Tuberculin Test (SICTT) were considered for study. The data consisted of 419 herds. Data were collected on all TB reactors and a random sample of 5 non-reactor cows in these herds: a data set of 4340 cows (2342 TB reactors and 1998 non-reactors). Previous milk data for the cows were taken into consideration and thus all lactations on a cow were analysed together with the years of lactations. There was an inherent hierarchical structure in the data, with lactations nested within cows and cows within herds and thus a linear mixed model with two random effects was used to describe the data. The results of this study showed that for all lactations and years under investigation, milk yield was significantly lower for TB reactor cows, with differences ranging from 120kg (2003, lactation 3) to 573kg (2001, lactation 1), when compared to the non-reactor cows.

Bovine tuberculosis as a model for human tuberculosis: advantages over small animal models.

For the development of vaccines and treatments against tuberculosis, animal models are needed. In this review, the pathogenesis and immune responses during human and bovine tuberculosis will be compared. Special attention will be paid to latency, because this feature has recently become the basis of specialized vaccines against latency antigens.

Systemic but not intra-intestinal vaccination with BCG reduces the severity of tuberculosis infection in ferrets (Mustela furo).

SETTING: Ferrets are important wildlife vectors of bovine tuberculosis (Mycobacterium bovis) in New Zealand. By reducing the severity and/or incidence of tuberculosis (TB) in wild ferret populations, vaccination may limit disease transmission to livestock. OBJECTIVE: To investigate whether vaccination of ferrets with attenuated M. bovis BCG via systemic or intraintestinal routes can reduce the severity of TB resulting from oral M. bovis challenge. DESIGN: Groups of captive ferrets were vaccinated with live BCG via sub-cutaneous injection or intra-duodenal inoculation, twice, 4 weeks apart. Vaccinated and non-vaccinated (control) ferrets were subsequently challenged orally with virulent M. bovis to simulate the natural route of infection. Peripheral blood lymphocyte reactivity was longitudinally monitored, and the outcome of challenge was determined 20 weeks later by autopsy, histology and bacteriological culture. RESULT: Both vaccination routes induced tuberculin-specific lymphocyte reactivity; however, only the subcutaneous route was effective in reducing disease. Subcutaneous vaccinated ferrets had a lower severity of infection than non-vaccinated control animals, as indicated by significant reductions in viable bacterial burdens and prevention of gross lesions in mesenteric lymph nodes (the primary site of infection), and a lower incidence of bacterial translocation to thoracic lymph nodes. However, sub-cutaneous vaccination did not reduce the incidence of mesenteric lymph node infection. CONCLUSIONS: Systemic vaccination with BCG can reduce the severity of TB resulting from oral challenge with virulent M. bovis; however, delivery of viable BCG to the upper intestinal tract may not protect ferrets against TB.

Effect of tuberculosis on milk production in dairy cows.

OBJECTIVE: To evaluate differences in milk production between cows with positive and negative caudal fold tuberculin test results in a Mycobacterium bovis-infected dairy herd. DESIGN: Cross-sectional epidemiologic survey. ANIMALS: 369 Holstein cows with lactation duration between 200 and 360 days. PROCEDURE: The caudal fold tuberculin test was performed. Information on milk production data, parity, calving season, days of lactation, previous milk production, and whether cows had clinical mastitis was obtained from farm records. Composite milk samples were collected and submitted for bacterial culture. RESULTS: 170 cows had positive tuberculin test results, and 199 had negative results. Cows with positive test results produced less milk (mean, 347 kg [763 lb]) than did cows with negative test results after adjusting for variables biologically related to milk production. Calving season (spring, summer) was significantly associated with reduced milk production. Cows with clinical mastitis produced less milk than did cows without clinical mastitis, but the difference was not statistically significant in the multiple regression analysis. CLINICAL IMPLICATIONS: In this herd, tuberculosis was associated with a 4% decrease in milk production. Milk production losses per cow attributable to calving season (spring, summer) were 3 times those attributable to tuberculosis. However, because of the high prevalence of tuberculosis in this herd, the impact of tuberculosis on total herd milk production was an additional cause for concern.

An outbreak of bovine tuberculosis in a free-living African buffalo (Syncerus caffer--sparrman) population in the Kruger National Park: a preliminary report.

Bovine tuberculosis was diagnosed for the first time in an African buffalo (Syncerus caffer) in the Kruger National Park (KNP). The index case was a 2-year-old, emaciated bull which had been found recumbent and obviously ill, near the south-western boundary of the KNP, in July 1990. During a follow-up random sampling of 57 buffalo, from two herds in close proximity to this initial case, nine more suspect cases were found. Mycobacterium bovis was isolated from a lung and thoracic lymph node, respectively, of two of these cases. Histopathologically, all nine of these animals had granulomatous lesions compatible with a diagnosis of mycobacteriosis, but acid-fast organisms could be demonstrated in only one animal.

Mycobacterial sepsis following intravesical instillation of bacillus Calmette-Guérin.

Intravesical bacillus Calmette-Guérin (BCG) administration for bladder cancer may lead to BCG dissemination in the compromised host. A case of a 63-year-old man with shock secondary to BCG sepsis is reported. The recognition and treatment of disseminated BCG infection are discussed. In addition to standard therapy for urosepsis, early therapy with steroids and coverage with antitubercular medications should be initiated for patients with this condition. In general, the author recommends that all febrile patients who have received BCG immunotherapy within three years, and who have no obvious source for their fever, have acid-fast bacilli blood cultures done for Mycobacterium bovis, and that these patients be admitted to the hospital for further evaluation.

[Preferential differentiation of hematopoietic stem cells transferred to mice previously infected by BCG]. / Différenciation préférentielle des cellules souches hématopoïétiques transférées chez des souris irradiées préalablement infectées par du BCG.

Following injection of bone marrow cells in lethally irradiated mice, previously infected with BCG regenerating hemopoietic cell populations differentiate along the leucocyte pathway to the detriment of erythroid lineage. Such a phenomenon persisting even if anemia of infected mice is increased by bleeding just before irradiation and reconstitution supports the hypothesis of preferential differentiation of stem cells.