Confronting the scientific obstacles to global control of tuberculosis

Young, Douglas B.; Perkins, Mark D.; Duncan, Ken; Barry, Clifton E.

doi:10.1172/jci34614

Cited by 283 publications

(253 citation statements)

References 106 publications

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“…New tuberculosis diagnostic techniques that can be used at all levels of the health system, particularly in people infected with HIV and in children, are urgently needed. 61 An example is the GeneXpert System (Cepheid, Sunnyvale, CA, USA), which is an M tuberculosis integrated nucleic acid amplifi cation test that uses a common platform to diagnose tuberculosis and rifampicin resistance. 62 With results provided in less than 2 h and with no risk of contamination, this system needs urgent evaluation in district hospitals, clinics, and microscopy centres.…”

Section: Intensifi Ed Case Fi Nding In Health Facilitiesmentioning

confidence: 99%

The HIV-associated tuberculosis epidemic—when will we act?

et al. 2010

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Journal LancetRights Reproduced on this site with permission of Elsevier Ltd. Please see [url] Tuberculosis 3The HIV-associated tuberculosis epidemic-when will we act? Anthony D Harries, Rony Zachariah, Elizabeth L Corbett, Stephen D Lawn, Ezio T Santos-Filho, Rhehab Chimzizi, Mark Harrington, Dermot Maher, Brian G Williams, Kevin M De Cock Despite policies, strategies, and guidelines, the epidemic of HIV-associated tuberculosis continues to rage, particularly in southern Africa. We focus our attention on the regions with the greatest burden of disease, especially sub-Saharan Africa, and concentrate on prevention of tuberculosis in people with HIV infection, a challenge that has been greatly neglected. We argue for a much more aggressive approach to early diagnosis and treatment of HIV infection in aff ected communities, and propose urgent assessment of frequent testing for HIV and early start of antiretroviral treatment (ART). This approach should result in short-term and long-term declines in tuberculosis incidence through individual immune reconstitution and reduced HIV transmission. Implementation of the 3Is policy (intensifi ed tuberculosis case fi nding, infection control, and isoniazid preventive therapy) for prevention of HIV-associated tuberculosis, combined with earlier start of ART, will reduce the burden of tuberculosis in people with HIV infection and provide a safe clinical environment for delivery of ART. Some progress is being made in provision of HIV care to HIV-infected patients with tuberculosis, but too few receive co-trimoxazole prophylaxis and ART. We make practical recommendations about how to improve this situation. Early HIV diagnosis and treatment, the 3Is, and a comprehensive package of HIV care, in association with directly observed therapy, short-course (DOTS) for tuberculosis, form the basis of prevention and control of HIV-associated tuberculosis. This call to action recommends that both HIV and tuberculosis programmes exhort implementation of strategies that are known to be eff ective, and test innovative strategies that could work. The continuing HIV-associated tuberculosis epidemic needs bold but responsible action, without which the future will simply mirror the past.

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Section: Intensifi Ed Case Fi Nding In Health Facilitiesmentioning

confidence: 99%

The HIV-associated tuberculosis epidemic—when will we act?

et al. 2010

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“…In a later work, Lehner's group have found that Mtb Hsp70 also binds to the chemokine receptor CCR5, which is the co-receptor for HIV-1 (Whittall et al 2006). The synergistic relationship between AIDS and tuberculosis is now seen as a major global health problem (Young et al 2008). It is therefore important to note that M. tuberculosis Hsp70 can dosedependently inhibit the infection of CD4 T cells by HIV-1, the active site in this protein being the C-terminal epitope 407-426.…”

Section: Hsp60mentioning

confidence: 99%

Unfolding the relationship between secreted molecular chaperones and macrophage activation states

Henderson

2009

Cell Stress and Chaperones

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Over the last 20 years, it has emerged that many molecular chaperones and protein-folding catalysts are secreted from cells and function, somewhat in the manner of cytokines, as pleiotropic signals for a variety of cells, with much attention being focused on the macrophage. During the last decade, it has become clear that macrophages respond to bacterial, protozoal, parasitic and host signals to generate phenotypically distinct states of activation. These activation states have been termed 'classical' and 'alternative' and represent not a simple bifurcation in response to external signals but a range of cellular phenotypes. From an examination of the literature, the hypothesis is propounded that mammalian molecular chaperones are able to induce a wide variety of alternative macrophage activation states, and this may be a system for relating cellular or tissue stress to appropriate macrophage responses to restore homeostatic equilibrium.

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“…The global eradication of tuberculosis remains a major goal of current disease control programs [1,2]. Mycobacterium bovis BCG, a live attenuated strain of M. bovis, has been used to prevent human tuberculosis since 1921 [3].…”

Section: Introductionmentioning

confidence: 99%

Modulation of pulmonary DC function by vaccine‐encoded GM‐CSF enhances protective immunity against Mycobacterium tuberculosis infection

et al. 2009

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The rational design of new vaccines engineered to target key components of the host immune response is crucial to aid control of important infectious diseases such as tuberculosis. In this report, we determined whether modifying the function of pulmonary APC could improve protection against infection with Mycobacterium tuberculosis. Targeted delivery to the lung of the cytokine GM‐CSF, expressed by the Mycobacterium bovis BCG vaccine strain, increased pulmonary DC numbers and secretion of the immunoregulatory cytokine IL‐12, compared with parental BCG immunization. This impact on APC number by BCG:GM‐CSF resulted in accelerated priming of antigen‐specific CD4+ T cells in the mediastinal lymph nodes and increased migration of activated CD4+ T cells into the lung. i.n. administration of BCG:GM‐CSF resulted in significantly increased protection against M. tuberculosis infection compared with mice vaccinated with BCG alone. BCG:GM‐CSF exhibited an improved safety profile, as immunodeficient RAG1−/− mice vaccinated i.n. with BCG:GM‐CSF survived significantly longer than control BCG‐vaccinated mice. These data demonstrate that manipulating immune cells in the lung by BCG‐based delivery of GM‐CSF can assist the development of protective mucosal immunity against pulmonary bacterial infection.

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Confronting the scientific obstacles to global control of tuberculosis

Cited by 283 publications

References 106 publications

The HIV-associated tuberculosis epidemic—when will we act?

The HIV-associated tuberculosis epidemic—when will we act?

Unfolding the relationship between secreted molecular chaperones and macrophage activation states

Modulation of pulmonary DC function by vaccine‐encoded GM‐CSF enhances protective immunity against Mycobacterium tuberculosis infection

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