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  1. 1
    Peer Reviewed

    Assessing the impact of defining a global priority research agenda to address HIV-associated tuberculosis.

    Odone A; Matteelli A; Chiesa V; Cella P; Ferrari A

    Tropical Medicine and International Health. 2016 Nov; 21(11):1420-1427.

    Objectives In 2010, the WHO issued 77 priority research questions (PRQs) to address HIV-associated TB. Objective of the this study was to assess the impact of defining the research agenda in stimulating and directing research around priority research questions. Methods We used number and type of scientific publications as a proxy to quantitatively assess the impact of research agenda setting. We conducted 77 single systematic reviews -one for every PRQ -building 77 different search strategies using PRQs’ keywords. Multivariate logistic regression models were applied to assess the quantity and quality of research produced over time and accounting for selected covariates. Results In 2009-2015, PRQs were addressed by 1631 publications (median: 11 studies published per PRQ, range 1-96). The most published area was ‘Intensified TB case finding’ (median: 23 studies/PRQ, range: 2-74). The majority (62.1%, n = 1013) were published as original studies, and more than half (58%, n = 585) were conducted in the African region. Original studies’ publication increased over the study period (P trend = <0.001). They focused more on the ‘Intensified TB case finding’ (OR = 2.17, 95% CI: 1.56-2.93) and ‘Drug-resistant TB and HIV infection’ (OR = 2.12, 95% CI: 1.47-3.06) areas than non-original studies. Original studies were published in journals of lower impact factor and received a smaller number of citations than non-original studies (OR = 0.54, 95% CI: 0.42-0.69). Conclusion The generation of evidence to address PRQs has increased over time particularly in selected fields. Setting a priority research agenda for HIV-associated TB might have positively influenced the direction and the conduct of research and contributed to the global response to such a major threat to health.
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  2. 2

    Engaging informal providers in TB control: what is the potential in the implementation of the WHO stop TB strategy? a discussion paper.

    Kaboru B; Uplekar M; Lonnroth K

    World Health and Population. 2011; 12(4):5-13.

    The World Health Organization (WHO) Stop TB Strategy calls for involvement of all healthcare providers in tuberculosis (TB) control. There is evidence that many people with TB seek care from informal providers before or after diagnosis, but very little has been done to engage these informal providers. Their involvement is often discussed with regard to DOTS (directly observed treatment - short course), rather than to the implementation of the comprehensive Stop TB Strategy. This paper discusses the potential contribution of informal providers to all components of the WHO Stop TB Strategy, including DOTS, programmatic management of multi-drug-resistant TB (MDR-TB), TB/HIV collaborative activities, health systems strengthening, engaging people with TB and their communities, and enabling research. The conclusion is that with increased stewardship by the national TB program (NTP), informal providers might contribute to implementation of the Stop TB Strategy. NTPs need practical guidelines to set up and scale up initiatives, including tools to assess the implications of these initiatives on complex dimensions like health systems strengthening.
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  3. 3
    Peer Reviewed

    Extreme condition, extreme measures? Compliance, drug resistance, and the control of tuberculosis.

    Harper I

    Anthropology and Medicine. 2010 Aug; 17(2):201-214.

    This paper explores the issue of compliance by focusing on the control of tuberculosis. In the last ten years, patient compliance in tuberculosis control has discursively shifted from 'direct observation' of therapy to more patient-centred focus and support drawing on rights-based approaches in dealing with health care provision. At the same time, there has been an increased international concern with the rise of drug resistant forms of tuberculosis, and how to manage this. This paper looks at these issues and the tensions between them, by discussing the shift in discourses around the two and how they relate. Drawing on experience from work in Nepal, and its successful tuberculosis control programme, it looks at debates around this and how these two arenas have been addressed. The rise of increasingly drug resistant forms of tuberculosis has stimulated the development of new WHO and other guidelines addressing how to deal with this problem. The links between public health, ethics and legal mandate are presented, and the implications of this for controlling transmission of drug resistant disease, on the one hand, and the drive for greater patient support mechanisms on the other. Looking forwards to uncertain ethical and public health futures, these issues will be mediated by emergent WHO and international frameworks.
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  4. 4

    Multidrug and extensively drug-resistant TB (M/XDR-TB): 2010 global report on surveillance and response.

    World Health Organization [WHO]. Stop TB Department

    Geneva, Switzerland, WHO, 2010. [71] p.

    This new report on anti-tuberculosis (TB) drug resistance by the World Health Organization (WHO) updates "Anti-tuberculosis drug resistance in the world: Report No. 4" published by WHO in 2008. It summarizes the latest data and provides latest estimates of the global epidemic of multidrug and extensively drug-resistant tuberculosis (M/XDR-TB). For the first time, this report includes an assessment of the progress countries are making to diagnose and treat MDR-TB cases. (Excerpt)
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  5. 5

    Fighting the tuberculosis epidemic in the Western Pacific region: current situation and challenges ahead.

    van Maaren PJ

    Kekkaku. 2010 Jan; 85(1):9-16.

    INTRODUCTION: Tuberculosis (TB) remains a major public health problem in the Western Pacific Region. More than 20% of the global burden of TB is found in the Region. In 2007, the latest year for which data is available, there were an estimated 1.9 million incident cases (109 per 100,000 population). Four countries (Cambodia, China, the Philippines and Vietnam) account for 93% of the total estimated incident cases in the Region. Every year an estimated 300 thousand persons die due to TB. The Region is host to an estimated 135,000 multi-drug resistant TB cases, most of which can be found in China. TB PREVALENCE AND TB MORTALITY: The Regional Stop TB strategy aims to halve the prevalence and mortality rates of 2000 by 2010. Based on current estimates, the TB prevalence declined with 24% between 2000 and 2007, while TB mortality declined with 19% in the same period. Given the current annual decrease in TB prevalence and mortality, it is unlikely that the Region will achieve the 50% reduction by 2010. CASE FINDING: Approximately 1.4 million new TB cases were notified in the Region in 2007, of which close to 0.7 million smear-positive cases. Cases from China accounted for 70% of the total notified smear-positive cases. The Regional case detection rate was sustained at 78%. Case detection rates in China, the Lao People's Democratic Republic, Mongolia, the Philippines and Vietnam exceeded the 70% target. TREATMENT OUTCOMES: A total of 92% of the 0.7 million new pulmonary smear-positive cases registered for treatment in 2006 were successfully treated. The treatment success rates exceed the 85% target in all countries with a high burden of TB, except Papua New Guinea where it was reported at 73%. MULTIDRUG-RESISTANT TB: In 2007, the proportion of MDR-TB in new TB cases was estimated to be 4%. A total of 135,411 MDR-TB cases was estimated to have occurred in 2007. Based on the overall case management data, 10,231 new patients and 1,596 re-treatment patients were reported with available drug susceptibility testing (DST) results in the Region. Of these, 1% (89/10,231) and 29% (468/1,596) had MDR-TB, respectively. Capacity to detect and treat MDR-TB cases is still very limited in most countries in the Region. Eighteen countries and areas in the Region have conducted drug resistance surveillance (DRS) since 2000, according to the Global Project on Anti-tuberculosis Drug Resistance Surveillance. Among new TB cases, the prevalence of multidrug-resistant TB (MDR-TB) ranged from 0% in Cambodia to 11.1% in the Commonwealth of the Northern Mariana Islands. MDR-TB prevalence among re-treatment cases ranged from 3.1% in Cambodia to 27.5% in Mongolia. In the five countries with a high burden of TB with available data from surveys (Cambodia, China, Mongolia, the Philippines, and Vietnam), MDR-TB prevalence in new cases and re-treatment cases ranged from 0% in Cambodia to 4.9% in China and from 3.1% in Cambodia to 27.5% in Mongolia, respectively. Notably, there were alarming rates of MDR-TB in several provinces in China among both new and retreatment cases. Increasing numbers of MDR-TB cases are reported from Papua New Guinea. TB-HIV CO-INFECTION: The overall estimated prevalence of HIV in new TB cases in 2007 was 2.7%. With 8.0% in 2008 compared to 11.8% in 2003, Cambodia shows a declining prevalence of HIV in new TB cases. There was a significant increase in the use of anti-retroviral therapy (ART) in the Region. However, detailed and complete data as well as strong collaboration in HIV and TB management are needed to be able to closely monitor the use of ART and its impact on TB-HIV co-infection in the Region. CONCLUSION: In spite of the substantial progress made in most countries with a high burden of TB, substantial challenges remain in the Region. The rate of decline in TB prevalence and mortality is too low to reach the 50% reduction goal in 2010. It will be necessary to further increase TB case detection and address the emerging spread of drug-resistant TB. The slow response in the most affected countries in the Region is a cause for concern. Strong commitment by national governments and their partners is needed to sustain and further strengthen the current TB control efforts.
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  6. 6
    Peer Reviewed

    Tuberculosis retreatment category predicts resistance in hospitalized retreatment patients in a high HIV prevalence area.

    Schreiber YS; Herrera AF; Wilson D; Wallengren K; Draper R; Muller J; Dawood H; Doucette S; Cameron DW; Alvarez GG

    International Journal of Tuberculosis and Lung Disease. 2009 Oct; 13(10):1274-80.

    SETTING: Rates of multidrug-resistant tuberculosis (MDR-TB) are currently as high as 7.7% in retreatment cases in KwaZulu-Natal, South Africa. MDR-TB prevalence is known to be high in patients categorized as treatment failures. Recent reports have questioned the effectiveness of the World Health Organization (WHO) Category II regimen in retreatment TB cases. OBJECTIVE: To determine whether treatment category predicts susceptibility patterns and outcomes in a hospitalized population of retreatment TB cases. DESIGN: Retrospective cohort of 197 pulmonary retreatment cases. RESULTS: Retreatment cases treated with the standard retreatment regimen had a high in-hospital mortality (19.8%), or poor outcome (26.4%) and a high rate of MDR-TB (16.2%). The 'treatment failure' category predicted resistance, with 57.1% of patients exhibiting any resistance compared to other treatment categories (P = 0.02); 53.8% of patients with any resistance experienced poor outcomes, compared to 16.6% of pan-susceptible cases (P = 0.02). There was a trend towards poor outcome in the treatment failure category (42.9%, P = 0.13). CONCLUSION: The retreatment category 'treatment failure' is associated with a high prevalence of resistance in an area of high human immunodeficiency virus (HIV) prevalence. The 'treatment failure' category should be used to identify patients who may benefit from alternative regimens using directed, intensified therapy or second-line agents instead of the current standard retreatment regimen.
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  7. 7
    Peer Reviewed

    Financial resources required for tuberculosis control to achieve global targets set for 2015.

    Floyd K; Pantoja A

    Bulletin of the World Health Organization. 2008 Jul; 86(7):568–576.

    The objective of this study was to estimate the financial resources required to achieve the 2015 targets for global tuberculosis (TB) control, which have been set within the framework of the Millennium Development Goals (MDGs). The Global Plan to Stop TB, 2006-2015 was developed by the Stop TB Partnership. It sets out what needs to be done to achieve the 2015 targets for global TB control, based on WHO's Stop TB Strategy. Plan costs were estimated using spreadsheet models that included epidemiological, demographic, planning and unit cost data. A total of US$ 56 billion is required during the period 2006-2015 (93% for TB-endemic countries, 7% for international technical agencies), increasing from US$ 3.5 billion in 2006 to US$ 6.7 billion in 2015. The single biggest cost (US$ 3 billion per year) is for the treatment of drug-susceptible cases in DOTS programmes. Other major costs are treatment of patients with multi- and extensively drug-resistant TB (MDR-TB and XDR-TB), collaborative TB/HIV activities, and advocacy, communication and social mobilization. Low-income countries account for 41% of total funding needs and 65% of funding needs for TB/HIV. Middle-income countries account for 72% of the funding needed for treatment of MDR-TB and XDR-TB. African countries require the largest increases in funding. Achieving the 2015 global targets set for TB control requires a major increase in funding. To support resource mobilization, comprehensive and costed national plans that are in line with the Global Plan to Stop TB are needed, backed up by robust assessments of the funding that can be raised in each country from domestic sources and the balance that is needed from donors. (author's)
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  8. 8

    Anti-tuberculosis drug resistance in the world. Fourth global report. The WHO / IUATLD Global Project on Anti-Tuberculosis Drug Resistance Surveillance, 2002-2007.

    Wright A; Zignol M

    Geneva, Switzerland, World Health Organization [WHO], 2008. [140] p. (WHO/HTM/TB/2008.394)

    This is the fourth report of the WHO/IUATLD Global Project on Anti-Tuberculosis Drug Resistance Surveillance. The three previous reports were published in 1997, 2000 and 2004 and included data from 35, 58 and 77 countries, respectively. This report includes drug susceptibility test (DST) results from 91,577 patients from 93 settings in 81 countries and 2 Special Administrative Regions (SARs) of China collected between 2002 and 2006, and representing over 35% of the global total of notified new smear-positive TB cases. It includes data from 33 countries that have never previously reported. New data are available from the following high TB burden countries: India, China, Russian Federation, Indonesia, Ethiopia, Philippines, Viet Nam, Tanzania, Thailand, and Myanmar. Between 1994 and 2007 a total of 138 settings in 114 countries and 2 SARs of China had reported data to the Global Project. Trend data (three or more data points) are available from 48 countries. The majority of trend data are reported from low TB prevalence settings; however this report includes data from three Baltic countries and 2 Russian Oblasts. Trend data were also available from 6 countries conducting periodic or sentinel surveys (Cuba, Republic of Korea, Nepal, Peru, Thailand, and Uruguay). (excerpt)
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  9. 9
    Peer Reviewed

    Kevin De Cock: Guiding HIV / AIDS policy at WHO.

    Shetty P

    Lancet Infectious Diseases. 2008 Feb; 8(2):98-100.

    Kevin De Cock is director of WHO's HIV/AIDS department. Formerly director of the US Centers for Disease Control and Prevention in Kenya, he is an infectious disease specialist, with expertise in HIV/ AIDS, tuberculosis, liver disease, and tropical diseases such as yellow fever and viral haemorrhagic fevers. TLID: How has your time as WHO's HIV/AIDS director been? KDC: It has been extremely interesting. AIDS policy is always challenging and changing. WHO's HIV efforts up to 2005 were very much oriented around the 3 by 5 initiative. The G8 in 2005 made an announcement about working towards universal access, which became an AIDS rallying cry. So we've had to reorganise ourselves around that as a theme. Some internal reorganisation was necessary to focus not only on treatment, but also on broader issues. We now have five key strategic directions: increasing access to HIV testing and counselling, maximising prevention, accelerating treatment scale-up, strengthening health systems, and investing in strategic information. We have also been working on some important technical areas. One is the issuing of guidance on both provider-initiated testing and male circumcision. In April, 2007, we also issued a report, in response to a request from the World Health Assembly, on the health sector's progress towards universal access. (excerpt)
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  10. 10

    Tuberculosis: international efforts and issues for Congress.

    Salaam-Blyther T

    [Washington, D.C.], United States Library of Congress, Congressional Research Service, 2007 Oct 26. 18 p. (CRS Report for Congress Order Code RL34246; USAID Development Experience Clearinghouse Doc. ID / Order No. PC-AAB-678)

    In 2005, TB prevalence rose only in sub-Saharan Africa and eastern Europe. WHO attributes a number of factors to this increase, including weak health systems, low-quality health care, minimal access to health facilities, insufficient staffing and little human resource development, ill-equipped and substandard laboratories, and limited coordination of TB and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) programs. In FY2008, Congress voted to fund U.S. global TB operations at unprecedented levels. The House FY2008 Foreign Operations Appropriations (H.R. 2764) provided $313.5 million for international TB programs and $300 million for a U.S. contribution to the Global Fund to Fight HIV/AIDS, TB, and Malaria (Global Fund). The Senate version of H.R. 2764 included $200 million for U.S. global TB efforts and $340 million for a U.S. contribution to the Global Fund. Both houses included $300 million in FY2008 Labor, HHS, and Education Appropriations (H.R. 3043 and S. 1710) for a U.S. contribution to the Global Fund. S. Rept.110-107 of S. 1710 also suggested that $10 million more than CDC's FY2007 operating plan for TB be provided to improve CDC's efforts to prevent TB and its progression into XDR-TB. No appropriations bills that include funds for TB efforts have been enacted. (excerpt)
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  11. 11
    Peer Reviewed

    Evaluating the potential impact of the new Global Plan to Stop TB: Thailand, 2004 -- 2005.

    Varma JK; Wiriyakitjar D; Nateniyom S; Anuwatnonthakate A; Monkongdee P

    Bulletin of the World Health Organization. 2007 Aug; 85(8):586-592.

    WHO's new Global Plan to Stop TB 2006-2015 advises countries with a high burden of tuberculosis (TB) to expand case-finding in the private sector as well as services for patients with HIV and multidrug-resistant TB (MDR-TB). The objective of this study was to evaluate these strategies in Thailand using data from the Thailand TB Active Surveillance Network, a demonstration project begun in 2004. In October 2004, we began contacting public and private health-care facilities monthly to record data about people diagnosed with TB, assist with patient care, provide HIV counselling and testing, and obtain sputum samples for culture and susceptibility testing. The catchment area included 3.6 million people in four provinces. We compared results from October 2004-September 2005 (referred to as 2005) to baseline data from October 2002-September 2003 (referred to as 2003). In 2005, we ascertained 5841 TB cases (164/100 000), including 2320 new smear-positive cases (65/100 000). Compared with routine passive surveillance in 2003, active surveillance increased reporting of all TB cases by 19% and of new smear-positive cases by 13%. Private facilities diagnosed 634 (11%) of all TB cases. In 2005, 1392 (24%) cases were known to be HIV positive. The proportion of cases with an unknown HIV status decreased from 66% (3226/4904) in 2003 to 23% (1329/5841) in 2005 (P< 0.01). Of 4656 pulmonary cases, mycobacterial culture was performed in 3024 (65%) and MDR-TB diagnosed in 60 (1%). In Thailand, piloting the new WHO strategy increased case-finding and collaboration with the private sector, and improved HIV services for TB patients and the diagnosis of MDR-TB. Further analysis of treatment outcomes and costs is needed to assess this programme's impact and cost effectiveness. (author's)
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  12. 12

    Drug resistance in tuberculosis [editorial]

    Ebrahim GJ

    Journal of Tropical Pediatrics. 2007 Jun; 53(3):147-149.

    Tuberculosis (TB) kills about 2 million adults and around 100 000 children every year. One-third of the world's population are currently infected with Mycobacterium tuberculosis and many have active disease. In Europe TB emerged as a major disease in the latter part of the 14th century. The industrial revolution saw rapid growth of urban centres where overcrowding with poor living conditions provided ideal circumstances for the spread of the disease. Great impact was made by streptomycin and isoniazid, so that by the 1970s TB was no longer being considered a problem in the developed world. But beginning in the 1980s the number of new cases of TB in USA and across Europe rose sharply. The pattern was repeated in many countries and worldwide throughout the 1990s and into the new millennium. The incidence of TB climbed to over 9 million cases every year. In 1993 the World Health Organization (WHO) declared TB as a global emergency. During the 1990s multidrug resistant tuberculosis (MDR-TB), defined as resistance to at least isoniazid and rifampicin, emerged as a threat to TB control. MDR-TB requires the use of second line drugs that are less effective, more toxic and costlier. In a global survey of 17 690 TB isolates during 2000-04, 20% were MDR and 2% were extremely drug resistant (XDR). XDR-TB is defined as MDR plus resistance to any fluoroquinolones and at least one of three injectable second line drugs kanamycin and amikacin, or capreomycin or both. Currently one in ten new infections is resistant to at least one antituberculosis drug. (excerpt)
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  13. 13
    Peer Reviewed

    Reaching the targets for tuberculosis control: the impact of HIV.

    Laserson KF; Wells CD

    Bulletin of the World Health Organization. 2007 May; 85(5):325-420.

    In 1991, the 44th World Health Assembly set two key targets for global tuberculosis (TB) control to be reached by 2000: 70% case detection of acid-fast bacilli smear-positive TB patients under the DOTS strategy recommended by WHO and 85% treatment success of those detected. This paper describes how TB control was scaled up to achieve these targets; it also considers the barriers encountered in reaching the targets, with a particular focus on how HIV infection affects TB control. Strong TB control will be facilitated by scaling-up WHO-recommended TB/HIV collaborative activities and by improving coordination between HIV and TB control programmes; in particular, to ensure control of drug-resistant TB. Required activities include more HIV counselling and testing of TB patients, greater use and acceptance of isoniazid as a preventive treatment in HIV-infected individuals, screening for active TB in HIV-care settings, and provision of universal access to antiretroviral treatment for all HIV-infected individuals eligible for such treatment. Integration of TB and HIV services in all facilities (i.e. in HIV-care settings and in TB clinics), especially at the periphery, is needed to effectively treat those infected with both diseases, to prolong their survival and to maximize limited human resources. Global TB targets can be met, particularly if there is renewed attention to TB/HIV collaborative activities combined with tremendous political commitment and will. (author's)
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  14. 14
    Peer Reviewed

    Barriers to reaching the targets for tuberculosis control: multidrug-resistant tuberculosis.

    Blondal K

    Bulletin of the World Health Organization. 2007 May; 85(5):325-420.

    The development and expansion of WHO's DOTS strategy was successful, with 83% of the world's population living in countries or parts of countries covered by this strategy by the end of 2004. Treatment success in the 2003 DOTS cohort of 1.7 million patients was 82% on average, close to the 85% target. Treatment success was below average in the African Region (72%), which can be partly attributed to occurrence of HIV co-infection, and in the European Region (75%), partly due to drug resistance. Drug resistance, specifically multidrug resistance and extensive drug resistance, is a serious threat to public health in all countries, especially in the Russian Federation, where the highest rates of multidrug resistance are presently accompanied by a rapid increase in HIV infection. Based on the experience of the first projects approved by the Green Light Committee, the treatment success of patients with multidrug-resistant tuberculosis (MDR-TB) is lower than that of drug-susceptible cases, but nevertheless reaches 70%. The collaborative effort of different organizations, professionals and communities is needed to address the development and spread of multidrug resistance and extensive drug resistance, which combined with the epidemic of HIV infection is one of the barriers to dealing effectively with TB. This effort should be directed towards facilitating the diagnosis and treatment of TB patients, in particular by improving access to drug susceptibility testing and strengthening treatment delivery by rigorous adherence to DOTS as outlined by the Stop TB Partnership. (author's)
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  15. 15
    Peer Reviewed

    Planning to improve global health: the next decade of tuberculosis control.

    Maher D; Dye C; Floyd K; Pantoja A; Lonnroth K

    Bulletin of the World Health Organization. 2007 May; 85(5):325-420.

    The Global Plan to Stop TB 2006-2015 is a road map for policy-makers and managers of national programmes. It sets out the key actions needed to achieve the targets of the Millennium Development Goals relating to tuberculosis (TB): to halve the prevalence and deaths by 2015 relative to 1990 levels and to save 14 million lives. Developed by a broad coalition of partners, the plan presents a model approach combining interventions that can feasibly be supplied on the ground. The main areas of activity set out in the plan are: scaling up interventions to control tuberculosis; promoting the research and development of improved diagnostics, drugs and vaccines; and engaging in related activities for advocacy, communications and social mobilization. Scenarios for the planning process were developed; these looked at issues both globally and in seven epidemiological regions. The scenarios made ambitious but realistic assumptions about the pace of scale-up and implementation coverage of the activities. A mathematical model was used to estimate the impact of scaling up current interventions based on data from studies of tuberculosis biology and from experience with tuberculosis control in diverse settings. The estimated costs of the activities set out in the Global Plan were based on implementing interventions and researching and developing drugs, diagnostics and vaccines; these costs were US$ 56 billion over 10 years. When translated into cost per disability adjusted life year averted, these costs compare favourably with those of other public health interventions. This approach to planning for global tuberculosis control is a valuable example of developing plans to improve global health that has relevance for other health issues. (author's)
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  16. 16
    Peer Reviewed

    Stopping tuberculosis proves hard to do.

    Lancet. 2007 Mar 24; 369(9566):965.

    Tuberculosis continues to kill nearly 2 million people every year, most of whom are in the lowest income countries. Since the launch of WHO's new Stop TB Strategy a year ago in this journal, three major threats to tuberculosis control can be identified: the spread of all forms of drug resistance, including extensively drug-resistant tuberculosis (XDR-TB); the challenges of successfully diagnosing and treating HIV-infected patients with tuberculosis; and the failure to attract sufficient funding to put all necessary control measures into place. These threats indicate that global tuberculosis control targets will not be met. The inexorable rise of drug-resistant strains (one in ten new infections is resistant to at least one antituberculosis drug), and the worrying spread of XDR-TB, threaten to undermine tuberculosis control efforts. 35 countries, including all those in the G8, have now confirmed XDRTB cases. But it is in South Africa that XDR-TB poses the greatest threat because of its particularlyhigh mortality in HIV-positive people--most patients will die before the diagnosis of XDR-TB can be confirmed. There are now 269 confirmed XDR-TB cases in South Africa, where it has spread from its place of first discovery last year, the province of KwaZulu Natal, to all parts of the country. There is a real danger that HIV infection will fast track the spread of XDR-TB into a global epidemic. According to Mario Raviglione, director of Stop TB at WHO, an appeal for US$95 million made last October to counter XDR-TB generated little response; WHO now estimates that $650 million is needed for multidrug-resistant tuberculosis and XDR-TB control in 2007 alone. (excerpt)
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  17. 17
    Peer Reviewed

    XDR tuberculosis spreads across South Africa.

    Kapp C

    Lancet. 2007 Mar 3; 369(9563):715-798.

    South Africa is struggling to contain an outbreak of extensively drug-resistant tuberculosis, which has now spread to all the country's provinces, according to the Department of Health, and threatens to hamper HIV/AIDS treatment plans. Clare Kapp reports from South Africa. WHO is sending a permanent staff member to be based in South Africa to advise authorities struggling with an outbreak of extensively drug-resistant (XDR) tuberculosis. The Department of Health says there have now been 269 confirmed cases of XDR tuberculosis and that it has spread from the province of KwaZulu-Natal, where it was first confirmed, to all parts of South Africa. But Karin Weyer, tuberculosis research director at the Medical Research Council (MRC), said nobody really knows the true number of cases because of laboratory and diagnostics constraints and inconsistencies in reporting. So far there have been no reported cases in neighbouring southern African countries, but Weyner believes that this is because they simply do not have the laboratory testing facilities. (excerpt)
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  18. 18
    Peer Reviewed

    Health-system reforms to control tuberculosis in China.

    Sleigh AC

    Lancet. 2007 Feb 24; 369(9562):626-627.

    In today's Lancet, Longde Wang and colleagues report on many remarkable recent improvements in the control of tuberculosis in China. The progress is good news in view of the size and global importance of the tuberculosis burden in China and the faltering of control in the 1990s, as noted by Wang. The fruitful partnership with WHO, the World Bank, the Global Fund to Fight AIDS, Tuberculosis and Malaria, and several governments and non-governmental organisations is also noteworthy, as is the commitment to transparent reporting and health-system reform in China today in the environment after the outbreak of severe acute respiratory syndrome. Better control of tuberculosis in China is also timely in view of the high rates of multidrug resistance, and the emergence of HIV infection in some population subgroups also at high risk of tuberculosis. One group of special concern are work migrants, most often poor young men, who leave the countryside to join the wage economy in towns and cities all over China. Some come from areas such as Henan Province where huge numbers of peasants were infected with HIV from scandalous plasma--donor practices in the 1990s. Many male migrants are at risk of unprotected sex when away from home. And men are also at higher risk of tuberculosis than women in China because the male-to-female ratio of adults with pulmonary tuberculosis is about 2:1 or more, reflecting a real risk excess rather than differential detection or notification. So several factors converge in young male migrant workers to put them at risk of both HIV and tuberculosis, and this convergence must be of great concern. (excerpt)
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  19. 19

    Guidelines for the programmatic management of drug-resistant tuberculosis.

    Rich M; Cegielski P; Jaramillo E; Lambregts K

    Geneva, Switzerland, World Health Organization [WHO], Stop TB Department, 2006. [184] p. (WHO/HTM/TB/2006.361)

    The emergence of resistance to drugs used to treat tuberculosis (TB), and particularly multidrug-resistant TB (MDR-TB), has become a significant public health problem in a number of countries and an obstacle to effective global TB control. In many other countries, the extent of drug resistance is unknown and the management of patients with MDR-TB is inadequate. In countries where drug resistance has been identified, specific measures need to be taken within TB control programmes to address the problem through appropriate management of patients and adoption of strategies to prevent the propagation and dissemination of drug-resistant TB, including MDR-TB. These guidelines offer updated recommendations for TB control programmes and medical workers in middle- and low-income countries faced with drug-resistant forms of TB, especially MDR-TB. They replace two previous publications by the World Health Organization (WHO) on drug-resistant TB. Taking account of important developments in recent years, the new guidelines aim to disseminate consistent, up-to-date recommendations for national TB control programmes and medical practitioners on the diagnosis and management of drug-resistant TB in a variety of geographical, political, economic and social settings. The guidelines can be adapted to suit diverse local circumstances because they are structured around a flexible framework approach, combining a consistent core of principles and requirements with various alternatives that can be tailored to the specific local situation. (excerpt)
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  20. 20

    The Stop TB Strategy: building on and enhancing DOTS to meet the TB-related Millennium Development Goals.

    Uplekar M; Figueroa-Munoz J; Floyd K; Getahun H; Jaramillo E

    Geneva, Switzerland, World Health Organization [WHO], 2006. 22 p. (WHO/HTM/STB/2006.37)

    Since the development of the DOTS strategy, WHO and partners have worked on complementary policies and strategies to address the remaining major constraints to achievement of global TB control targets. These include expanding access to diagnosis and treatment through community TB care, and public--private mix (PPM) approaches aimed at engaging all care providers -- state and non-state -- in DOTS implementation. Innovative mechanisms such as the Global Drug Facility and the Green Light Committee have been developed to improve access to quality-assured and affordable drugs in resource-poor settings. The collaborative activities that need to be implemented by TB and HIV/AIDS control programmes have been defined, and strategies for managing multidrug-resistant TB (MDR-TB) have been developed and tested. Impact assessment is being pursued as a means of evaluating progress towards the MDGs. New partnerships and academic research initiatives for development of new tools are beginning to produce results and several new diagnostics, drugs and candidate vaccines are in the pipeline. (excerpt)
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  21. 21

    Instructions for applying to the Green Light Committee for access to second-line anti-tuberculosis drugs.

    Blondal K; Caminero JA; Cegielski P; Espinal MA; Jaramillo E

    [Geneva, Switzerland], World Health Organization [WHO], 2006. 15 p. (WHO/HTM/TB/2006.369)

    Controlling multi-drug resistant tuberculosis (MDR-TB) is one of the six components of the WHO Stop TB strategy. Although prevention must be the highest priority for TB control programmes, many countries have patients with drug-resistant TB who must be treated too. Such countries should take specific measures to gradually incorporate appropriate strategies for treatment of this form of tuberculosis into their programmes and prevent propagation of drug-resistant TB. Misuse of second-line anti-TB drugs results in further resistance to these same second-line drugs, creating incurable forms of tuberculosis. It is imperative that second-line anti-TB drugs are used wisely. The WHO Guidelines For The Programmatic Management of Drug Resistant Tuberculosis (herein after referred to as the Guidelines) provide recommendations for appropriate management of drug-resistant TB so as not to generate further drug resistance. To help programmes develop and implement develop and implement strategies for the management of drug resistant TB, the Green Light Committee for Access to Second-line Anti-tuberculosis Drugs (GLC) was created by WHO and its partners in January 2000. (excerpt)
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  22. 22
    Peer Reviewed

    Epidemiology of antituberculosis drug resistance (the Global Project on Anti-tuberculosis Drug Resistance Surveillance): an updated analysis.

    Aziz MA; Wright A; Laszlo A; De Muynck A; Portaels F

    Lancet. 2006 Dec 16; 368(9553):2142-2154.

    The burden of tuberculosis is compounded by drug-resistant forms of the disease. This study aimed to analyse data on antituberculosis drug resistance gathered by the WHO and International Union Against Tuberculosis and Lung Disease Global Project on Anti-tuberculosis Drug Resistance Surveillance. Data on drug susceptibility testing for four antituberculosis drugs--isoniazid, rifampicin, ethambutol, and streptomycin--were gathered in the third round of the Global Project (1999-2002) from surveys or ongoing surveillance in 79 countries or geographical settings. These data were combined with those from the first two rounds of the project and analyses were done. Countries that participated followed a standardised set of guidelines to ensure comparability both between and within countries. The median prevalence of resistance to any of the four antituberculosis drugs in new cases of tuberculosis identified in 76 countries or geographical settings was 10.2% (range 0.0-57.1). The median prevalence of multidrug resistance in new cases was 1.0% (range 0.0-14.2). Kazakhstan, Tomsk Oblast (Russia), Karakalpakstan (Uzbekistan), Estonia, Israel, the Chinese provinces Liaoning and Henan, Lithuania, and Latvia reported prevalence of multidrug resistance above 6.5%. Trend analysis showed a significant increase in the prevalence of multidrug resistance in new cases in Tomsk Oblast (p < 0.0001). Hong Kong (p = 0.01) and the USA (p = 0.0002) reported significant decreasing trends in multidrug resistance in new cases of tuberculosis. Multidrug resistance represents a serious challenge for tuberculosis control in countries of the former Soviet Union and in some provinces of China. Gaps in coverage of the Global Project are substantial, and baseline information is urgently required from several countries with high tuberculosis burden to develop appropriate control interventions. (author's)
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  23. 23

    XDR-TB -- a global threat [editorial]

    Lancet. 2006 Sep 16; 368(9540):964.

    Following an emergency consultation in Johannesburg on Sept 7 and 8, global health agencies have developed a seven-point plan to combat extensively (or extremely) drug-resistant tuberculosis (XDR-TB). Representatives from several southern African countries have agreed to implement the plan within 3 months. Multidrug-resistant TB (MDR-TB), defined as resistance to at least isoniazid and rifampicin, requires the use of second-line drugs that are less effective, more expensive, and more toxic than first-line regimens based on isoniazid and rifampicin. Recognised earlier this year, XDR-TB is MDR-TB that is also resistant to three or more of the six classes of second-line drugs. Of 17 690 TB isolates taken between 2000 and 2004, 20% were MDR and 2% were XDR. XDR-TB has now been identified in all regions of the world but is most prevalent in Asia and in eastern Europe. (excerpt)
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  24. 24
    Peer Reviewed

    Multidrug-resistant tuberculosis management in resource-limited settings.

    Nathanson E; Lambregts-van Weezenbeek C; Rich ML; Gupta R; Bayona J

    Emerging Infectious Diseases. 2006 Sep; 12(9):1389-1397.

    Evidence of successful management of multidrugresistant tuberculosis (MDRTB) is mainly generated from referral hospitals in high-income countries. We evaluate the management of MDRTB in 5 resource-limited countries: Estonia, Latvia, Peru, the Philippines, and the Russian Federation. All projects were approved by the Green Light Committee for access to quality-assured second-line drugs provided at reduced price for MDRTB management. Of 1,047 MDRTB patients evaluated, 119 (11%) were new, and 928 (89%) had received treatment previously. More than 50% of previously treated patients had received both first- and second-line drugs, and 65% of all patients had infections that were resistant to both first- and second-line drugs. Treatment was successful in 70% of all patients, but success rate was higher among new (77%) than among previously treated patients (69%). In resource-limited settings, treatment of MDRTB provided through, or in collaboration with, national TB programs can yield results similar to those from wealthier settings. (author's)
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  25. 25
    Peer Reviewed

    Reaching the targets for TB control: call for papers.

    Blanc L; Martinez L

    Bulletin of the World Health Organization. 2006 Sep; 84(9):688.

    Tuberculosis (TB) has been a major killer disease for several thousand years. Despite intensive efforts to combat the disease over the past twenty years, TB remains one of the leading causes of morbidity and mortality in many settings, particularly in the world's poorest countries. TB is primarily a disease of poverty, but is a significant public health problem also in wealthier countries where pockets of poverty and marginalized population groups exist. It is estimated that around 1.7 million people die each year from TB; and in 2004 figures indicate that approximately 8.9 million people developed the disease. (excerpt)
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