Mycobacterium tuberculosis-specific CD8+ T cells are functionally and phenotypically different between latent infection and active disease.

Eur J Immunol. 2013 Mar 4;

Authors: Rozot V, Vigano S, Mazza-Stalder J, Idrizi E, Day CL, Perreau M, Lazor-Blanchet C, Petruccioli E, Hanekom W, Goletti D, Bart PA, Nicod L, Pantaleo G, Harari A

Abstract
Protective immunity to Mycobacterium tuberculosis (Mtb) remains poorly understood and the role of Mtb-specific CD8+ T cells is controversial. Here we performed a broad phenotypic and functional characterization of Mtb-specific CD8+ T cells in 326 subjects with latent Mtb infection (LTBI) or active TB disease (TB). Mtb-specific CD8+ T cells were detected in most (60%) TB patients and few (15%) LTBI subjects but were of similar magnitude. Mtb-specific CD8+ T cells in LTBI subjects were mostly TEMRA cells (CD45RA+ CCR7- ), co-expressing 2B4 and CD160, and in TB patients were mostly TEM cells (CD45RA- CCR7- ), expressing 2B4 but lacking PD-1 and CD160. The cytokine profile was not significantly different in both groups. Furthermore, Mtb-specific CD8+ T cells expressed low levels of perforin and granulysin but contained granzymes A and B. However, in vitro-expanded Mtb-specific CD8+ T cells expressed perforin and granulysin. Finally, Mtb-specific responses were less frequently detected in extrapulmonary TB compared with pulmonary TB patients. Mtb-specific CD8+ T-cell proliferation was also greater in patients with extrapulmonary compared with pulmonary TB. Thus, the activity of Mtb infection and clinical presentation are associated with distinct profiles of Mtb-specific CD8+ T-cell responses. These results provide new insights in the interaction between Mtb and the host immune response.

PMID: 23456989 [PubMed - as supplied by publisher]

Global epidemiology of tuberculosis.

Semin Respir Crit Care Med. 2013 Feb;34(1):3-16

Authors: Glaziou P, Falzon D, Floyd K, Raviglione M

Abstract
With 1.4 million deaths in 2011 and 8.7 million new cases, tuberculosis (TB) disease remains a global scourge. Global targets for reductions in the epidemiological burden of TB have been set for 2015 and 2050 within the context of the Millennium Development Goals (MDGs) and by the Stop TB Partnership. Achieving these targets is the focus of national and international efforts in TB control, and demonstrating whether or not they are achieved is of major importance to guide future and sustainable investments.This paper discusses the methods used to estimate the global burden of TB; estimates of incidence, prevalence, and mortality for 2011, combined with assessment of progress toward the 2015 targets for reductions in these indicators based on trends since 1990 and projections up to 2015; trends in TB notifications and in the implementation of the Stop TB Strategy; and prospects for elimination of TB by 2050.

PMID: 23460002 [PubMed - in process]

Tuberculosis and HIV Coinfection.

Semin Respir Crit Care Med. 2013 Feb;34(1):32-43

Authors: Gray JM, Cohn DL

Abstract
The human immunodeficiency virus (HIV) pandemic has amplified the global burden of tuberculosis (TB), particularly in sub-Saharan Africa, where 82% of the world's TB/HIV coinfection exists. HIV infection significantly increases the risk of developing and dying from TB and was associated with 350,000 TB deaths in 2010. The diagnosis of HIV-associated TB is often challenging due to atypical clinical and radiographic manifestations, more frequent extrapulmonary disease, and higher rates of smear-negative pulmonary TB. Nucleic acid amplification tests, including the Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA), improve our ability to rapidly diagnose both smear-negative and extrapulmonary TB. The standard 6-month anti-TB regimen is usually adequate for HIV coinfected persons, but intermittent dosing in the intensive phase should be avoided because of an increased risk of relapse with acquired rifamycin resistance. The comanagement of HIV and TB is challenging due to drug-drug interactions, overlapping drug toxicities, concerns about adherence, and the immune reconstitution inflammatory syndrome. However, the initiation of antiretroviral therapy (ART) during the course of TB treatment is necessary to improve survival, and the appropriate timing of ART is dependent on the level of immune suppression. Therefore, the management of TB must be well coordinated with HIV resources, prepared to rapidly diagnose HIV, assess immune status, and correctly treat both infections.

PMID: 23460004 [PubMed - in process]

Management of multidrug resistant tuberculosis.

Semin Respir Crit Care Med. 2013 Feb;34(1):44-59

Authors: Daley CL, Caminero JA

Abstract
Drug-resistant strains of Mycobacterium tuberculosis have emerged as a major threat to global tuberculosis control. Despite the availability of curative antituberculosis therapy for nearly half a century, inappropriate and inadequate treatment has allowed M. tuberculosis to acquire resistance to our most important antituberculosis drugs. The epidemic of drug-resistant tuberculosis has spread quickly in some areas due to the convergence of resistant strains of M. tuberculosis in high-risk patients (e.g., those with human immunodeficiency virus/acquired immunodeficiency syndrome) and high-risk environments (e.g., hospitals and prisons). The World Health Organization (WHO) estimates that there were 650,000 cases of multidrug resistant tuberculosis (MDR-TB) in 2010, defined as strains that are resistant to at least isoniazid (INH) and rifampicin (RIF). Globally, WHO estimates that 3.7% of new tuberculosis cases and 20% of re-treatment cases have MDR-TB. By the end of 2012, 84 countries had reported at least one case of extensively drug resistant strains (XDR-TB), which are MDR-TB strains that have acquired additional resistance to fluoroquinolones and at least one second-line injectable. Recently, cases of "totally drug resistant" tuberculosis have been reported. It is estimated that only 10% of all MDR-TB cases are currently receiving therapy and only 2% are receiving quality-assured drugs. This article reviews the management of MDR and XDR-TB and highlights the updated 2011 WHO guidelines on the programmatic management of drug-resistant tuberculosis.

PMID: 23460005 [PubMed - in process]