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Development of vaccines against bovine tuberculosis.

Bovine tuberculosis caused by Mycobacterium bovis remains an economically important problem in Great Britain with potential zoonotic consequences, and the incidence is rising exponentially. In 1997 an independent scientific review recommended that the best option for disease control in Great Britain was the development of a cattle vaccine. Bovine tuberculosis remains a significant problem in countries of the developing world. Indeed, more than 94% of the world's population live in countries in which the control of bovine tuberculosis in buffalos or cattle is limited or absent. Effective vaccination strategies would have a major impact in countries that cannot afford expensive test and slaughter-based control strategies. Here, we present a review of progress toward that goal, and discuss how this progress has shaped our research strategy for the development of a vaccine.

Animals↗

A cost-benefit analysis of culling badgers to control bovine tuberculosis.

Bovine tuberculosis (TB) is an important economic problem. The incidence of TB in cattle herds has steadily risen in the UK, and badgers are strongly implicated in spreading disease. Since the mid-1970s the UK government has adopted a number of badger culling strategies to attempt to reduce infection in cattle. In this report, an established model has been used to simulate TB in badgers, transmission to cattle, and control by badger culling. Costs were supplied by the UK Government's Department for Environment Food and Rural Affairs (Defra) for badger trapping and gassing. Regardless of culling intensity or area simulated, an overall reduction in the herd breakdown rate was seen. With a high culling efficacy and no social perturbation, the mean Net Present Value of a few simulated culling strategies in an "ideal world" was positive, meaning the economic benefits outweighed the costs. Further work is required before these results could be considered definitive, as it is necessary to evaluate uncertainties and simulate less than perfect conditions.

Animals↗

The sensitivity of gross necropsy, caudal fold and comparative cervical tests for the diagnosis of bovine tuberculosis.

Bovine tuberculosis (bTb) was diagnosed in 22 cattle herds in the northeast comer of Michigan's lower peninsula. Of these 22 herds, 494 animals in 7 herds were examined by gross necropsy, histopathologic exam, mycobacterial culture, and polymerase chain reaction (PCR) assay performed only on samples that were histologically compatible for bTb. Results of culture and PCR assay interpreted in parallel were used as the reference test for calculation of the sensitivity of 1) the caudal fold test (CFT), 2) the caudal fold and comparative cervical skin tests used in series (CFTCCTSER), and 3) gross necropsy. Mycobacterium bovis was isolated from 43 animals. Using all 7 herds, the sensitivities of the CFT, the CFTCCTSER, and gross necropsy were 93.02%, 88.37%, and 86.05%, respectively. When the data were stratified by low- and moderate-prevalence herds, the sensitivities were 83.33%, 75.0%, and 83.33% in low-prevalence herds and 96.77%, 93.55%, and 87.10% in moderate-prevalence herds. The sensitivities of the 2 skin tests were slightly higher when 2 or more gross lesions were present, and the sensitivity of gross necropsy was significantly higher (P = 0.049). The sensitivity of the CFT was found to be notably higher than most estimates in other studies; however, a direct comparison was not possible because the amount of purified protein derivative and the reference methods were different in this study compared with other published studies. Although the sensitivities are high, 2 of the 7 herds (29%) would have had 1 or more positive animals left in the herd if a test-and-removal program had been used. This suggests that when positive herds are identified, selective culling of skin test reactors is a less acceptable disease control strategy than is complete depopulation.

Animals↗

Antibiotic resistant tuberculosis and bovine tuberculosis in an Irish hospital population (1991 to 2001).

Of 864 consecutive culture positive cases of tuberculosis (TB) treated in the period 1991-2001, a total of 19 (2.1%) were M. bovis and 32 (3.7%) were drug resistant - Multi-Drug Resistant Tuberculosis (MDR-TB) (8); poly drug resistant (7); mono drug resistant (17). Iatrogenic factors were important in the cause of resistance in 9 cases (4 cases of MDR-TB): in 6 cases patients factors were important. Comparison with previous report for the period 1982-1985 showed relatively more isolates of M. bovis (p = 0.02); drug resistant TB (p = 0.005); and MDR-TB (p = 0.01) in the current study. Comparison with the background population of TB patients showed that patients with resistant TB were more likely to have a previous history of TB (Relative Risk = 3.58) and more likely to be foreign nationals (Relative Risk = 1.93) We conclude that while overall incidence of TB has declined that in relative terms the caseload of drug resistant TB and MDR-TB has increased. The drug cost of treating MDR-TB may be as high as 44,900 euros per patient.

Adolescent↗

[Role of Mycobacterium tuberculosis in bovine tuberculosis].

The authors report the results of a survey on the possible role of human Mycobacterium in the ganglio-pulmonary tuberculosis of bovines. 232 bovines seized in the abattoirs of Algiers over a period of 8 months were concerned by this work. The results obtained showed that microscopic examination was negative in 50% of cases. This result was expected as ganglionary lesions are paucibacillary. Cultures were also negative in 50% of cases, 25% of them were contaminated. 50% rate of positive cultures was obtained when Loewenstein-Jensen medium with 1% pyruvate was used. Morphological and biochemical identification showed that out of 113 strains, 7 were Mycobacterium tuberculosis (6.2%). In seems therefore that Mycobacterium tuberculosis, human pathogen, is also pathogenic for bovines. Its frequent occurrence could be explained by the high prevalence of human tuberculosis in Algeria.

Animals↗

Vaccination with DNA vaccines encoding MPB70 or MPB83 or a MPB70 DNA prime-protein boost does not protect cattle against bovine tuberculosis.

SETTING: Bovine tuberculosis is a problem in a number of countries and protection of cattle by vaccination could be an important control strategy. OBJECTIVES: To determine the ability of DNA vaccines, which express the mycobacterial antigens MPB83 and MPB70 and a DNA prime-protein boost strategy to stimulate immune responses in cattle and protect against bovine tuberculosis. DESIGN: Groups of cattle (n=10) were vaccinated with MPB83 DNA, MPB70 DNA, or MPB70 DNA followed by MPB70 protein or injected with BCG or control plasmid DNA. Animals were challenged intratracheally with virulent Mycobacterium bovis at 13 weeks and protection assessed 17 weeks later at postmortem. RESULTS: In contrast to the strong cellular immune responses induced by BCG, the DNA vaccines induced minimal interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) responses. Cattle primed with MPB70 DNA and boosted with MPB70 protein induced a strong antibody response and a weak IFN-gamma response. BCG gave significant reduction in four pathological parameters of disease while the DNA vaccines and MPB70 DNA/protein did not protect animals against challenge with M. bovis. Moreover, cattle vaccinated with MPB70 DNA/protein had a significantly higher proportion of animals with severe lung lesions (>100 lesions) than the MPB70 DNA alone or the control group. Increased bovine PPD-specific IL-4 mRNA expression in cattle, post-challenge, correlated with the presence of tuberculous lung lesions. CONCLUSION: Vaccination of calves with MPB70 or MPB83 DNA vaccines or with a more immunogenic MPB70 DNA prime-protein boost strategy did not induce protection against bovine tuberculosis.

Animals↗

Natural infection of red deer with bovine tuberculosis.

Six bovine tuberculosis-free red deer hinds were introduced in October 1993 to a 1.8 ha enclosure, within a larger field study site known to contain tuberculous possums, and kept there for 9 months. A Mycobacterium bovis-infected possum was found in the vicinity of the deer enclosure 3 weeks after the introduction. Subsequently, a further eleven infected possums were found in the area. The deer were monitored by repeated composite antibody detection ELISA and lymphocyte transformation assays for tuberculosis, interpreted in parallel, by skin testing and by routine culturing of samples collected from potential excretion sites. Lymphocyte transformation assay evidence of M. bovis infection in four hinds was first observed 4 months after introduction. One other hind became bovine tuberculin lymphocyte transformation assay positive in the 5th month. Positive or equivocal bovine reactivity remained evident at most test episodes. A comparative cervical skin test performed in July 1994, shortly before slaughter, was positive in these five hinds. Mycobacterium bovis was recovered off swabs from the oropharyngeal tonsils of two hinds during routine sampling. Detailed necropsy of the six deer revealed a single typical tuberculous lesion in only one, but culturing of various tissue specimens ascertained that the five blood test and comparative cervical skin test-positive animals were all infected. Mycobacterium bovis was cultured from the oropharyngeal tonsils of four and medial retropharyngeal lymph nodes of two of the deer with no typical gross lesions. Six additional tuberculosis-free hinds were introduced to the enclosure in April 1994 and kept there for 12 months. Four of these animals showed a positive lymphocyte transformation assay response to M. bovis after 9 weeks, but no significant reactivity thereafter. Concurrent observational studies suggest that five of the first six deer probably became infected through close inspection and investigation of the tuberculous possums, although the possibility of deer-to-deer transmission cannot be totally excluded. The likely deer-possum contact, and thus exposure to M. bovis, was related to the curiosity and social ranking of the hinds. The second group appear to have had transient exposure to M. bovis, possibly caused by direct contact with the infected hinds introduced earlier. This group never showed any curiosity toward, or interaction with, possums during the periods of observation.

Journal Article↗