Mycobacterium avium subsp. paratuberculosis (basonym M. paratuberculosis) is the causative agent of paratuberculosis, a chronic enteritis of ruminants. To control the considerable economic effect that paratuberculosis has on the livestock industry, a vaccine that induces protection with minimal side effects is required. We employed transposon mutagenesis and allelic exchange to develop three potential vaccine candidates, which were then tested for virulence with macrophages, mice, and goats. All three models identified the WAg906 mutant as being the most attenuated, but some differences in the levels of attenuation were evident among the models when testing the other strains. In a preliminary mouse vaccine experiment, limited protection was induced by WAg915, as evidenced by a reduced bacterial load in spleens and livers 12 weeks following intraperitoneal challenge with M. paratuberculosis K10. While we found macrophages and murine models to be rapid and cost-effective alternatives for the initial screening of M. paratuberculosis mutants for attenuation, it appears necessary to do the definitive assessment of attenuation with a ruminant model.
Following pre-migration screening for tuberculosis (TB), migrants who are deemed to be at a high risk of developing TB must attend post-entry follow-up in Australia. We aimed to evaluate the effectiveness of post-migration TB follow-up in the state of New South Wales to diagnose TB in these high-risk migrants.In this retrospective cohort study, we assessed the risk of TB in migrants who arrived in New South Wales between 2000 and 2015 and were referred for post-migration follow-up. Clinical notes were examined for a nested cohort to determine whether TB was diagnosed via the follow-up programme or via passive case finding.Of the 32 550 migrants referred for follow-up, 428 (1.3%) developed TB. The incidence of TB was 436 per 100 000 person-years (95% CI 384–491 per 100 000 person-years) in the first 2 years after arrival and 128 per 100 000 person-years (95% CI 116–140 per 100 000 person-years) over the mean study observation period of 10.3 years. An estimated 63% of cases were diagnosed via follow-up. TB notifications occurred 0.55 years earlier since time of arrival in Australia in migrants who attended follow-up than in those who did not.Post-migration follow-up detected 63% of TB cases in high-risk migrants and potentially prevented delay of TB diagnosis.
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