Bovine tuberculosis--another view from down under.
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Animals↗
Biomedical subjects
D M Collins
Publications and source records attributed to D M Collins.
Continuing Mycobacterium bovis transmission from animals to humans in New Zealand.
New Zealand has a large reservoir of Mycobacterium bovis infection in wild and farmed animals. This study aimed to assess the extent of human infection with this organism and the potential contribution of these animal sources. Combined epidemiological and laboratory investigation of human tuberculosis cases over the period 1995-2002 showed that M. bovis accounted for 2.7% (54/1997) of laboratory-confirmed human tuberculosis cases, a rate of 0.2/100,000 population. M. bovis isolates from humans (23) were typed using restriction endonuclease analysis (REA) and compared with isolates from wild and domestic animals (2600). Fourteen (61%) of the human isolates had REA patterns that were identical to patterns for isolates from cattle, deer, possums, ferrets, pigs, and occasionally cats. These results suggest a low level of ongoing M. bovis transmission from animal reservoirs to humans in New Zealand.
Adult↗
Quantifying badger exposure and the risk of bovine tuberculosis for cattle herds in county Kilkenny, Ireland.
The objectives of the study were to quantify the levels of badger exposure for cattle and to test the hypothesis that increased badger exposure does not increase the risk of bovine tuberculosis (BTB) in a herd. Information that became available from the targeted removal of badgers over the study period, and from a badger-removal project in county Kilkenny, during 1996-1999 was used. The specific location of cattle within each farm, and the length of time that cattle spent in each farm field during the grazing season, and in the barnyard during winter, was used to build an exposure coefficient to quantify the amount of badger exposure that cattle encountered either on pasture or in the barn. The study design was a matched case-control study in which the control herds were selected using incidence density sampling. During the 4-year study period, 543 badgers were removed and of these 96 badgers were classified as tuberculosis positive; 96 BTB herd breakdowns occurred. There was a significant association between case herds and having a higher badger sett exposure coefficient during 1996-1998. No significant association between case herds and having a higher exposure coefficient based on the number of badgers, or the number of tuberculous badgers, during September 1997-December 1999 was found.
Animals↗
Differences of gene expression in bovine alveolar macrophages infected with virulent and attenuated isogenic strains of Mycobacterium bovis.
Infection with Mycobacterium bovis is a significant human and animal health problem in many parts of the world. The first stage of pulmonary tuberculosis occurs after inhalation of the bacilli into an alveolus where they are ingested by resident macrophages. DNA microarray analysis was used to detect genes expressed in bovine lung alveolar macrophages infected with two isogenic strains of M. bovis, a virulent strain, ATCC35723 and an attenuated strain, WAg520 derived from ATCC35723. Chemokines, interleukin-8 and monocyte chemotactic protein 1, were more strongly expressed in ATCC35723-infected macrophages compared to WAg520-infected macrophages. Conversely, a group of genes, including fibrinogen-like protein 2 and legumain, were expressed at a higher level in macrophages infected with WAg520 compared to ATCC35723. Quantitative real-time PCR of a selected group of these differentially expressed genes confirmed enhanced levels of IL-8 mRNA in ATCC35723-infected macrophages compared to WAg520-infected macrophages. Microarray analysis of gene expression in macrophages infected with attenuated isogenic strains of M. bovis may identify key genes involved in early and protective immune responses to tuberculosis.
Animals↗
Use of a polymerase chain reaction to subtype Mycobacterium avium subspecies paratuberculosis, an increasingly important pathogen from farmed deer in New Zealand.
AIMS: To review the number of microbiologically-confirmed cases of Johne's disease in farmed deer since 2000, and determine the prevalence of the bovine and ovine subtypes of Mycobacterium avium subsp paratuberculosis (M. paratuberculosis), using a highly specific polymerase chain reaction (PCR) test on samples from infected herds. METHODS: The number of cases of M. paratuberculosis in farmed deer identified by culture or IS900 PCR was documented. A highly specific PCR test was applied to subtype M. paratuberculosis from BACTEC 12B cultures selected on the basis of one culture per deer herd, to give a wide coverage of herds in New Zealand. RESULTS: From January 2001 to October 2005, M. paratuberculosis was isolated from 1,141 farmed deer, and has now been identified by microbiological testing in over 600 deer herds in New Zealand. The bovine subtype of M. paratuberculosis was shown by a highly specific PCR test to be present in 91/95 herds examined; the ovine subtype was found in the remaining four herds. CONCLUSIONS: Since 2000, there has been a substantial increase in both the number of microbiologically-confirmed cases of Johne's disease in farmed deer and the number of infected herds. Johne's disease is now widespread and common in deer herds throughout New Zealand. Whilst the bovine subtype of M. paratuberculosis predominates in deer herds in New Zealand in which Johne's disease has been confirmed, the occasional finding of the ovine subtype highlights the need to consider both sheep and cattle as potential sources of infection for farmed deer.
Animals↗
Advances in understanding disease epidemiology and implications for control and eradication of tuberculosis in livestock: the experience from New Zealand.
A deteriorating tuberculosis problem in cattle and deer in New Zealand has been halted and then reversed over the last decade. Mycobacterium bovis infection in both wild and domestic animal populations has been controlled. This has been achieved by applying a multi-faceted science-based programme. Key features of this have been a comprehensive understanding of the epidemiology of tuberculosis in animals, confidence in sampling wild animal populations, effective application of diagnostic tests in cattle and deer, and the ability to map M. bovis genotypes.
Animal Population Groups↗
In vitro evaluation of concurrent use of commercially available insect repellent and sunscreen preparations.
BACKGROUND: Insect repellents and sunscreens are over-the-counter products extensively used by the general public. Concurrent application of these products has become widespread in many regions across North America, because of concerns about West Nile virus and skin cancers. OBJECTIVES: We investigated whether formulation type, application amount, and sequence would affect the percutaneous absorption profiles of the active repellent and sunscreen ingredients. METHODS: In vitro percutaneous permeation of the repellent N,N-diethyl-m-toluamide (DEET) and the sunscreen oxybenzone from concurrent application of five commercially available products (A, repellent spray; B, repellent lotion; C, sunscreen lotion; D and E, combined repellent/sunscreen lotions) was measured and compared using Franz-style diffusion cells with piglet skin at 37 degrees C. RESULTS: Penetration of DEET in A and B increased by 1640% and 282%, respectively, when C was applied concurrently. Penetration of DEET in D and E was 53% and 79% higher than that in B. Permeation of DEET from A + C (2:1) and A + C (1: 2) increased by 530% and 278%, respectively. Permeation of oxybenzone was 189% and 280% higher in A + C and B + C than in C. Permeation of oxybenzone in D and E was also 221% and 296% higher than that in C. Permeation of oxybenzone was 196% greater when A was applied on top of C than when C was applied on top of A, while oxybenzone in A + C (1:2) permeated 171% more than that in A + C (2:1). CONCLUSIONS: Concurrent application of commercially available repellent and sunscreen products resulted in significant synergistic percutaneous permeation of the repellent DEET and the sunscreen oxybenzone in vitro. The percutaneous penetration profiles were dependent upon the type of formulation, application sequence and application proportion.
Administration, Topical↗
The efficacy of live tuberculosis vaccines after presensitization with Mycobacterium avium.
The variable efficacy of BCG in humans has been extensively documented but its cause is still not well understood. One possible reason for this variation is the effect of presensitization with environmental mycobacteria. To investigate in guinea pigs the effects of presensitization with well characterized Mycobacterium avium strains on the vaccine efficacy of BCG and of two recently developed, avirulent strains of Mycobacterium bovis. Two strains of M. avium containing the DNA insertion element IS901 (M. avium+) and two strains not containing this element (M. avium-) were inoculated subcutaneously or by oral administration into guinea pigs to assess their virulence in these animals and their ability to induce delayed type hypersensitivity to tuberculins. Subsequently, groups of guinea pigs presensitized with orally administered M. avium+ and M. avium- and a control group were vaccinated with BCG, or one of two newly attenuated strains of M. bovis. All groups were then challenged by the aerosol route with virulent M. bovis. Vaccine efficacy was assessed 5 weeks later by the presence of macroscopic lesions and bacterial counts of spleen and lung. No macroscopic lesions were observed in any of the guinea pigs inoculated with strains of M. avium+ or M. avium- and all animals gave delayed-type hypersensitivity skin-test reactions to avian PPD. In the vaccine experiment, presensitization with orally administered M. avium+ alone produced a low level of protection against subsequent challenge with virulent M. bovis. In the absence of presensitization with M. avium or after presensitization with an M. avium- strain, BCG and two attenuated strains of M. bovis produced significant levels of protection. No additional protection was observed in lungs of guinea pigs presensitized with M. avium+ and subsequently vaccinated with BCG. In contrast, both newly attenuated strains of M. bovis induced significant protection in lungs after such presensitization. Presensitization of guinea pigs by the oral administration of M. avium+ provides a model for testing vaccines under conditions where the efficacy of BCG has been compromised by prior sensitization with environmental mycobacteria.
Animals↗
Use of administrative healthcare claims to examine the effectiveness of trimethoprim-sulfamethoxazole versus fluoroquinolones in the treatment of community-acquired acute pyelonephritis in women.
OBJECTIVE: To evaluate the effectiveness of trimethoprim-sulfamethoxazole and fluoroquinolones in the treatment of community-acquired acute pyelonephritis. PATIENTS AND METHODS: We identified a population-based cohort of non-pregnant women aged 18-65 years, initially treated with trimethoprim-sulfamethoxazole or a fluoroquinolone for community-acquired pyelonephritis in an ambulatory care setting. Subjects were identified from a healthcare claims database in Manitoba, Canada for the period 15 February 1996 to 31 March 1999. Subsequent treatment failure, as evidenced by the provision of additional treatment up to 42 days post-diagnosis, was compared between the two treatments. RESULTS: A total of 1084 women met inclusion criteria: 653 (60.2%) treated with trimethoprim-sulfamethoxazole and 431 (39.8%) treated with a fluoroquinolone. Treatment outcomes were affected by subject age. At age 20, treatment with a fluoroquinolone resulted in a reduced probability of treatment failure compared with trimethoprim-sulfamethoxazole (odds ratio, 0.56; 95% CI, 0.33-0.97). At age 60, there was no difference in the probability of treatment failure (odds ratio, 1.61; 95% CI, 0.82-3.16). No other subject characteristics impacted comparative effectiveness; however, several characteristics increased the odds of treatment failure irrespective of the initial antibiotic. These included: recent urinary tract infection (odds ratio, 2.07; 95% CI, 1.14-3.57), recent antibiotic use (odds ratio, 1.40; 95% CI, 1.00-1.96;), and a treatment duration of less than 10 days (odds ratio, 2.18; 95% CI, 1.59-2.99). CONCLUSION: Younger subjects ( approximately 20 years) treated with fluoroquinolones were less likely to experience treatment failure than those treated with trimethoprim-sulfamethoxazole. Treatment durations of less than 10 days resulted in a higher probability of treatment failure regardless of the initial antibiotic.
Adolescent↗
Mycobacterial diseases of deer.
The most significant mycobacterial diseases of free-living, captive and farmed deer are bovine tuberculosis, caused by Mycobacterium bovis, Johne's disease (paratuberculosis), caused by Mycobacterium avium subsp paratuberculosis (basonym M. paratuberculosis), and avian tuberculosis, caused principally by M. avium subsp avium. The first case of M. bovis infection in farmed deer was identified in New Zealand in 1978. In 1983, a voluntary scheme was introduced in New Zealand to control tuberculosis in farmed deer, followed by a compulsory tuberculosis control scheme in 1990. The primary control measure is the slaughter of infected animals, detected by skin testing and blood testing, together with movement control and vector control. The number of infected deer herds peaked in the mid 1990s at over 160 herds, but by 30 June 2002 this had been reduced to 79 (1.45%), and to 67 (1.23%) by June 2003. Deer-to-deer transmission occurs, but the majority of herd breakdowns are believed to be from infected vectors. Factors likely to affect the susceptibility of deer include age, environment, population density, exposure and genetics. Avian tuberculosis occasionally causes clinical disease in wild, captive and farmed deer in New Zealand and overseas. Mycobacterium intracellulare, and subspecies of M. avium other than M. paratuberculosis, are widespread throughout New Zealand and are thought to be largely responsible for the high level of sensitisation to avian purified protein derivative (PPD), which is used for comparison purposes in tuberculosis skin testing of deer in this country. Infections with these organisms are usually subclinical in farmed deer, although M. avium subsp avium commonly causes lesions in retropharyngeal, mesenteric and ileocaecal lymph nodes. These lesions cause problems because of their gross and microscopic similarity to those due to M. bovis infection. Birds and domestic animals are most likely to become infected via environmental contamination of food, water, bedding litter or soil, while carnivores or scavengers may also become infected by ingesting infected carcasses. Johne's disease has been reported in deer in the wild and in zoos, especially in North America, the United Kingdom (UK) and Europe. Since first being confirmed in farmed deer in New Zealand in 1979, the incidence of Johne's disease has increased steadily. To date, M. paratuberculosis has been identified in >600 farmed deer on 300 properties. The majority of cases have been identified from suspected tuberculous lesions submitted from deer slaughter plants. Clinically, Johne's disease in deer is similar to the disease in sheep and cattle, with typical signs of loss of weight and condition, and diarrhoea. However, outbreaks of Johne's disease frequently occur in young red deer, 8-15 months of age, whereas the clinical disease in sheep and cattle is sporadic and usually affects adults 3-5 years of age. The disease is characterised by a chronic granulomatous enteritis and lymphadenitis, especially affecting the jejunum and ileum and the mesenteric lymph nodes. Deer affected subclinically may have lesions in these lymph nodes at slaughter, which are grossly indistinguishable from those due to bovine tuberculosis. Because of the antigenic similarity between M. intracellulare and all the subspecies of M. avium, including M. paratuberculosis, the diagnostic tests for Johne's disease lack sensitivity and specificity, making control difficult.
Journal Article↗
Vaccine and skin testing properties of two avirulent Mycobacterium bovis mutants with and without an additional esat-6 mutation.
SETTING: Molecular techniques are now available to develop new live tuberculosis vaccines by producing avirulent strains of the Mycobacterium tuberculosis complex with known genes deleted. OBJECTIVES: Determine if removal of esat-6 from new live tuberculosis vaccines with known attenuating mutations affects their vaccine efficacy and if it could enable the development of discriminating diagnostic tests. DESIGN: Remove the esat-6 gene by allelic exchange from two illegitimate mutants of Mycobacterium bovis that had previously been shown to have similar vaccine efficacy to BCG in a guinea pig vaccination model. Determine the effect this removal has on virulence, vaccine efficacy and skin test reactivity in guinea pigs. RESULTS: Two double knockout strains of M. bovis were produced and their virulence and vaccine efficacy were compared to their parent strains. Removal of the esat-6 gene had no significant effect on vaccine efficacy. In skin tests, animals inoculated with the double knockout strains reacted to PPD but not ESAT-6, whereas those inoculated with the parent strains had similar skin test reactivity to both PPD and esat-6. CONCLUSION: Removal of esat-6 from new live tuberculosis vaccine candidates has no significant effect on vaccine properties but does enable the use of skin tests to distinguish between vaccination and infection.
Animals↗
A DNA prime-live vaccine boost strategy in mice can augment IFN-gamma responses to mycobacterial antigens but does not increase the protective efficacy of two attenuated strains of Mycobacterium bovis against bovine tuberculosis.
The Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine has variable efficacy for both human and bovine tuberculosis. There is a need for improved vaccines or vaccine strategies for control of these diseases. A recently developed prime-boost strategy was investigated for vaccination against M. bovis infection in mice. BALB/c and C57BL/6 mice were primed with a DNA vaccine, expressing two mycobacterial antigens, ESAT-6 and antigen 85 A and boosted with attenuated M. bovis strains, BCG or WAg520, a newly attenuated strain, prior to aerosol challenge. Before challenge, the antigen-specific production of interferon-gamma (IFN-gamma) was evaluated by ELISPOT and antibody responses were measured. The prime-boost stimulated an increase in the numbers of IFN-gamma producing cells compared with DNA or live vaccination alone, but this varied according to the attenuated vaccine strain, time of challenge and the strain of mouse used. Animals vaccinated with DNA alone generated the strongest antibody response to mycobacterial antigens, which was predominantly IgG1. BCG and WAg520 alone generally gave a 1-2 log10 reduction in bacterial load in lungs or spleen, compared to non-vaccinated or plasmid DNA only control groups. The prime-boost regimen was not more effective than BCG or WAg520 alone. These observations demonstrate the comparable efficacy of BCG and WAg520 in a mouse model of bovine tuberculosis. However, priming with the DNA vaccine and boosting with an attenuated M. bovis vaccine enhanced IFN-gamma immune responses compared to vaccinating with an attenuated M. bovis vaccine alone, but did not increase protection against a virulent M. bovis infection.
Animals↗
The re-emergence of Mycobacterium bovis infection in brushtail possums (Trichosurus vulpecula) after localised possum eradication.
AIM: To examine the spatial and temporal pattern of Mycobacterium bovis (bovine tuberculosis) infection in a population of brushtail possums (Trichosurus vulpecula) after localised possum eradication. METHODS: Possums on a 36 ha site were eradicated and re-population from the surrounding area studied using population surveys conducted approximately every 2 months for 40 months from the cessation of eradication activity (month zero), using a capture-release programme. At each trapping session, all possums were examined for clinical signs of tuberculosis. The diagnosis of tuberculosis was confirmed by the isolation of M. bovis, and restriction endonuclease analysis (REA) was used to type the isolates. Infected possums were categorised as residents (present on the site for at least 6 months before diagnosis), range expanders (adult possums which had extended their nearby home ranges to become trappable within the study site), or juvenile immigrants (sub-adult possums which had dispersed into the site from an unknown distance away). This classification was used to identify the location where possums became infected. Capture locations and denning site locations were used to examine the spatial pattern of disease occurrence. RESULTS: Thirty cases of tuberculosis were diagnosed among the 370 possums identified on the study site. Four different REA types (Types 2, 3, 8 and 10) were identified. The first two cases of tuberculosis were diagnosed in Month 4, in mature male possums categorised as range expanders, the third case was diagnosed in Month 6 and the fourth case at Month 9. Each of the first four cases was infected with a different REA type. The subsequent temporal pattern of infection was consistent with transmission from range expander cases and dispersing juvenile immigrants to resident possums. Clinical incidence remained low but persistent until the third year, when the incidence of Types 2, 8 and 10 escalated. Type 3 infections showed an earlier incidence peak, but disappeared from the site when the last known case died at Month 20. Of the dispersing juvenile possums entering the site, four became clinically tuberculous and represented a source of re-infection of other possums. CONCLUSIONS: Re-emergence of tuberculosis after localised possum eradication was due to the continuing reintroduction of infection in mature and immature diseased possums, and not the survival of M. bovis in the environment.
Journal Article↗
New generation vaccines and delivery systems for control of bovine tuberculosis in cattle and wildlife.
Advances in the understanding of protective immune responses to tuberculosis are providing opportunities for the rational development of improved vaccines for bovine tuberculosis. Protection requires activation of macrophages through stimulation of a Th 1 type immune response. Ideally, a vaccine for cattle should induce protection without causing animals to react in a tuberculin test when exposed to Mycobacterium bovis. A number of new tuberculosis vaccines including attenuated M. bovis strains, killed mycobacteria, protein and DNA vaccines have been developed and many of these are being assessed in cattle. The requirements for a tuberculosis vaccine for wildlife differ from those for cattle. The major goal of a wildlife vaccine is to prevent the transmission of M. bovis to cattle and other wildlife. Although there are a number of technical problems associated with the development of a vaccine delivery system for wildlife, attenuated M. bovis vaccines administered via oral baits or aerosol spray to possums have already been shown to reduce the severity of a subsequent M. bovis infection.
Animals↗
Accidental Mycobacterium bovis infection in a veterinarian.
CASE: A veterinarian developed tenosynovitis and secondary carpal tunnel syndrome following accidental inoculation of Mycobacterium bovis during the necropsy of a tuberculous possum from Westland, New Zealand. CLINICAL RELEVANCE: M. bovis infection is a zoonotic disease, and occupational exposure to tuberculous animals places people at risk of contracting the disease. CONCLUSIONS: Adhering to safe work practices reviewed in this article is important to minimise the risk of infection to people handling tuberculous animals.
Journal Article↗
Production of avirulent mutants of Mycobacterium bovis with vaccine properties by the use of illegitimate recombination and screening of stationary-phase cultures.
A better tuberculosis vaccine is urgently required to control the continuing epidemic. Molecular techniques are now available to produce a better live vaccine than BCG by producing avirulent strains of the Mycobacterium tuberculosis complex with known gene deletions. In this study, 1000 illegitimate recombinants of Mycobacterium bovis were produced by illegitimate recombination with fragments of mycobacterial DNA containing a kanamycin resistance gene. Eight recombinant strains were selected on the basis of their inability to grow when stationary-phase cultures were inoculated into minimal medium. Five of these recombinants were found to be avirulent when inoculated into guinea pigs. Two of the avirulent recombinants produced vaccine efficacy comparable to BCG against an aerosol challenge in guinea pigs with M. bovis. One of these recombinants had an inactivated glnA2 gene encoding a putative glutamine synthetase. Transcriptional analysis showed that inactivation of glnA2 did not affect expression of the downstream glnE gene. The other recombinant had a block of 12 genes deleted, including the sigma factor gene sigG. Two avirulent recombinants with an inactivated pckA gene, encoding phosphoenolpyruvate carboxykinase which catalyses the first step of gluconeogenesis, induced poor protection against tuberculosis. It is clear that live avirulent strains of the M. tuberculosis complex vary widely in their ability as vaccines to protect against tuberculosis. Improved models may be required to more clearly determine the difference in protective effect between BCG and potential new tuberculosis vaccines.
Animals↗
Identification of a cadmium-induced gene in Mycobacterium bovis and Mycobacterium tuberculosis.
A 17-kDa protein (CadI) was induced by cadmium in Mycobacterium bovis and Mycobacterium tuberculosis. Comparison of the N-terminal sequence from M. bovis CadI with the annotated M. tuberculosis genome database identified Rv2641 as the encoding gene. Long and short promoter fragments from M. bovis cadI were fused to the lacZ reporter gene in pYUB76. Only the long fragment directed cadmium-inducible activity when electroporated into M. bovis. The cadI promoter has potential for both constitutive and inducible expression studies in M. bovis and M. tuberculosis.
Amino Acid Sequence↗
Virulence factors of Mycobacterium bovis.
Virulence factors of Mycobacterium bovis are the special properties that enable it to infect, survive, multiply and cause disease in an animal host. An understanding of these factors will lead to new strategies including an effective vaccine to control bovine tuberculosis. A few factors have already been identified and two broadly different approaches to discover other virulence factors are now being used. In the first approach, libraries of random M. bovis mutants are produced, the likely attenuated mutants are identified using a screening technique and the interrupted genes in selected mutants are identified. In the second approach, genes encoding putative virulence factors are selected by a range of different methods and then inactivated, usually by allelic exchange, to produce likely attenuated mutants of M. bovis. In both approaches, loss of virulence by a mutant must be determined in an animal model. Subsequently, the mutant must be complemented back to virulence with an active form of the identified gene in order to demonstrate that loss of virulence was not due to polar effects of the mutation on nearby genes. It is almost certain that most of the virulence factors of M. bovis are the same as those of the classical human tuberculosis organism, Mycobacterium tuberculosis, as both organisms can cause identical clinical disease in humans and are genetically very similar. Many putative virulence genes are now being investigated and only the inherent slowness with which mycobacterial work proceeds, delays the inevitable arrival of an exciting new phase in the understanding of mycobacterial disease.
Alleles↗