#Tuberculosis: An Infection-Initiated #Autoimmune Disease?

http://www.cell.com/trends/immunology/fulltext/S1471-4906(16)30141-7

However, key steps in TB pathogenesis remain poorly understood. We propose that autoimmunity is a critical and overlooked process driving pathology in TB, and present clinical and experimental observations supporting this hypothesis.

Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice #Guidelines: Diagnosis of #Tuberculosis in Adults and Children

http://m.cid.oxfordjournals.org/content/early/2016/12/08/cid.ciw694.full

These guidelines are not intended to impose a standard of care. They provide the basis for rational decisions in the diagnosis of tuberculosis in the context of the existing evidence.

#Tuberculosis Among #foreign born Persons Diagnosed ≥10 Years After Arrival in the United States, 2010–2015
https://www.cdc.gov/mmwr/volumes/66/wr/mm6611a3.htm

The majority of tuberculosis (TB) cases in the United States are attributable to reactivation of latent TB infection (LTBI) (1). LTBI refers to the condition when a person is infected with Mycobacterium tuberculosis without signs and symptoms, or radiographic or bacteriologic evidence of TB disease. Promoting testing for TB infection as part of routine primary care among groups at high risk is crucial for advancing TB prevention and elimination initiatives in the United States. Emphasis should be focused on persons who have lived in countries with high TB prevalence, including persons who have resided in the United States for ≥10 years.

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Phase 2b Controlled Trial of M72/AS01E #Vaccine to Prevent #Tuberculosis

https://www.nejm.org/doi/full/10.1056/NEJMoa1803484

A total of 1786 participants received M72/AS01E and 1787 received placebo, and 1623 and 1660 participants in the respective groups were included in the according-to-protocol efficacy cohort. A total of 10 participants in the M72/AS01E group met the primary case definition (bacteriologically confirmed active pulmonary tuberculosis, with confirmation before treatment), as compared with 22 participants in the placebo group (incidence, 0.3 cases vs. 0.6 cases per 100 person-years). The vaccine efficacy was 54.0% (90% confidence interval CI, 13.9 to 75.4; 95% CI, 2.9 to 78.2; P=0.04). Results for the total vaccinated efficacy cohort were similar (vaccine efficacy, 57.0%; 90% CI, 19.9 to 76.9; 95% CI, 9.7 to 79.5; P=0.03). There were more unsolicited reports of adverse events in the M72/AS01E group (67.4%) than in the placebo group (45.4%) within 30 days after injection, with the difference attributed mainly to injection-site reactions and influenza-like symptoms. Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two groups.

CONCLUSIONS
M72/AS01E provided 54.0% protection for M. tuberculosis–infected adults against active pulmonary tuberculosis disease, without evident safety concerns

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Intestinal #dysbiosis compromises alveolar macrophage immunity to Mycobacterium #tuberculosis

https://www.nature.com/articles/s41385-019-0147-3

Current treatments for tuberculosis (TB) are effective in controlling Mycobacterium tuberculosis (Mtb) growth, yet have significant side effects and do not prevent reinfection. Therefore, it is critical to understand why our host defense system is unable to generate permanent immunity to Mtb despite prolonged anti-tuberculosis therapy (ATT).

Here, we demonstrate that treatment of mice with the most widely used anti-TB drugs, rifampicin (RIF) or isoniazid (INH) and pyrazinamide (PYZ), significantly altered the composition of the gut microbiota. Unexpectedly, treatment of mice with the pro-Mtb drugs INH and PYZ, but not RIF, prior to Mtb infection resulted in an increased bacterial burden, an effect that was reversible by fecal transplantation from untreated animals.

Collectively, these data indicate that dysbiosis induced by ATT administered to millions of individuals worldwide may have adverse effects on the anti-Mtb response of alveolar macrophages.

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Prevention of #tuberculosis in macaques after intravenous BCG immunization

Mycobacterium tuberculosis (Mtb) is the leading cause of death from infection worldwide. The only available vaccine, BCG (Bacillus Calmette–Guérin), is given intradermally and has variable efficacy against pulmonary tuberculosis, the major cause of mortality and disease transmission. Here we show that intravenous administration of BCG profoundly alters the protective outcome of Mtb challenge in non-human primates (Macaca mulatta).

Compared with intradermal or aerosol delivery, intravenous immunization induced substantially more antigen-responsive CD4 and CD8 T cell responses in blood, spleen, bronchoalveolar lavage and lung lymph nodes. Moreover, intravenous immunization induced a high frequency of antigen-responsive T cells across all lung parenchymal tissues. Six months after BCG vaccination, macaques were challenged with virulent Mtb.

Notably, nine out of ten macaques that received intravenous BCG vaccination were highly protected, with six macaques showing no detectable levels of infection, as determined by positron emission tomography–computed tomography imaging, mycobacterial growth, pathology and granuloma formation. The finding that intravenous BCG prevents or substantially limits Mtb infection in highly susceptible rhesus macaques has important implications for vaccine delivery and clinical development, and provides a model for defining immune correlates and mechanisms of vaccine-elicited protection against tuberculosis.

https://go.nature.com/3apnOqq