Development of a standardised multidrug-resistant/extensively drug-resistant tuberculosis assessment and monitoring tool

Fondazione S Maugeri, Care and Research Institute, World Health Organization Collaborating Centre for TB and Lung Diseases, Tradate, Italy.
The International Journal of Tuberculosis and Lung Disease (Impact Factor: 2.32). 10/2009; 13(10):1305-8.
Source: PubMed


Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) threaten global TB control. The MDR/XDR-TB Assessment and Monitoring Tool was developed to standardise evaluations of country capacity to prevent, diagnose and treat MDR/XDR-TB and identify program gaps. It provides data to guide national plans, generates baseline data to measure progress, provides information for Green Light Committee (GLC) and Global Fund to Fight AIDS, Tuberculosis and Malaria applications, guides technical assistance and informs donor investment. In field testing, the tool scoring system performed equally well in high- and low-prevalence settings. This GLC-endorsed tool supports global efforts to contain MDR/XDR-TB and is useful in developing national MDR/XDR-TB control strategies.

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    ABSTRACT: The emergence of multidrug-resistant (MDR) and, more recently, of extensively drug resistant (XDR) strains of Mycobacterium tuberculosis is a real threat to achieve tuberculosis (TB) control and elimination globally. More than 510,000 new cases of MDR-TB occur each year and XDR-TB cases are recognized in every setting where there has been the capacity to detect them, particularly in Eastern Europe. MDR- and XDR-TB control in Europe and the United States are heavily affected by what happens globally, as the majority of cases occurring in these countries originate in high TB-burden areas of the world. Scaling-up of culture- and drug susceptibility testing capacities and the expanded use of high-technology assays for rapid determination of resistance represent the prerequisites to achieve better control of MDR- and XDR-TB. Most cases with MDR- and XDR-TB in Europe and the United States can be treated successfully if well-designed regimens based on available second- and third-line anti-TB drugs are used and surgical options are carefully considered. Nevertheless, the development of new (more effective and less toxic) drugs to treat patients infected by MDR- and XDR-TB strains with or without active disease are urgently needed. Adherence to internationally agreed standards of care and control practices is imperative to achieve TB control.
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    ABSTRACT: Mycobacterium tuberculosis continues to be a leading cause of death by an infectious agent world wide with approximately two million deaths attributable to it annually. Once infected, the host mounts a robust Th1 type immune response that contains, but does not eliminate the bacteria. A small percentage (5-10%) fail to contain the infection, develop active disease, and are contagious. Most remain asymptomatic and are considered latently infected. BCG, while the gold standard for vaccination, ultimately appears to limit disease, but not prevent infection. In addition, chemotherapeutic treatment is long, requires multiple agents, and compliance is difficult to maintain. With one third the world's population infected, inadequate vaccine efficacy, and difficult treatment regimen, it is imperative that a better understanding of which factors are responsible for containment of the infection be achieved. CD4 T cells are an essential component of the immune response that controls M. tuberculosis. CD4 T cells are able to both promote inflammation and dampen its effect. As a pro-inflammatory Th1 cell, these cells secrete pro-inflammatory cytokines, participate in macrophage and dendritic cell activation and help prime CD8 T cells. As regulatory T cells, CD4 T cells prevent autoimmunity and may act to protect surrounding tissue from immunopathologic damage. One main function of pro-inflammatory CD4 T cells is IFNγ production, however other cells can and do produce IFNγ. In addition, the role of regulatory T cells during infection and how they relate to disease progression has yet to be elucidated. The work presented in this dissertation provides a new model for addressing the role of IFNγ from sources other than CD4 T cells, and addresses what pro-inflammatory functions they may have in addition to IFNγ production. In addition, these studies address regulatory T cells and the anti-inflammatory effects of long term IL-12 treatment as well as Treg's relationship to disease outcome in non-human primates.
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