[Show abstract][Hide abstract] ABSTRACT: Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3-4 month isoniazid plus rifampicin; or 3-4 month rifampicin alone.
European Respiratory Journal 09/2015; DOI:10.1183/13993003.01245-2015 · 7.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Multidrug-resistant tuberculosis (MDR-TB) (resistance to at least isoniazid and rifampicin) will influence the future of global TB control. 88% of estimated MDR-TB cases occur in middle- or high-income countries, and 60% occur in Brazil, China, India, the Russian Federation and South Africa.
The World Health Organization collects country data annually to monitor the response to MDR-TB. Notification, treatment enrolment and outcome data were summarised for 30 countries, accounting for >90% of the estimated MDR-TB cases among notified TB cases worldwide.
In 2012, a median of 14% (interquartile range 6–50%) of estimated MDR-TB cases were notified in the 30 countries studied. In 15 of the 30 countries, the number of patients treated for MDR-TB in 2012 (71 681) was >50% higher than in 2011. Median treatment success was 53% (interquartile range 40–70%) in the 25 countries reporting data for 30 021 MDR-TB cases who started treatment in 2010.
Although progress has been noted in the expansion of MDR-TB care, urgent efforts are required in order to provide wider access to diagnosis and treatment in most countries with the highest burden of MDR-TB.
European Respiratory Journal 09/2014; 45(1). DOI:10.1183/09031936.00101814 · 7.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In order to inform the development of appropriate strategies to improve financial risk protection, we conducted a systematic literature review of the financial burden of tuberculosis (TB) faced by patients and affected families.
The mean total costs ranged from $55 to $8198, with an unweighted average of $847. On average, 20% (range 0–62%) of the total cost was due to direct medical costs, 20% (0–84%) to direct non-medical costs, and 60% (16–94%) to income loss. Half of the total cost was incurred before TB treatment. On average, the total cost was equivalent to 58% (range 5–306%) of reported annual individual and 39% (4–148%) of reported household income. Cost as percentage of income was particularly high among poor people and those with multidrug-resistant TB. Commonly reported coping mechanisms included taking a loan and selling household items.
The total cost of TB for patients can be catastrophic. Income loss often constitutes the largest financial risk for patients. Apart from ensuring that healthcare services are fairly financed and delivered in a way that minimises direct and indirect costs, there is a need to ensure that TB patients and affected families receive appropriate income replacement and other social protection interventions.
European Respiratory Journal 02/2014; 43(6). DOI:10.1183/09031936.00193413 · 7.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: People with TB and/or HIV frequently experience severe economic barriers to health care, including out-of-pocket expenses related to diagnosis and treatment, as well as indirect costs due to loss of income. These barriers can both aggravate economic hardship and prevent or delay diagnosis, treatment and successful outcome, leading to increased transmission, morbidity and mortality. WHO, UNAIDS and the ILO argue that economic support of various kinds is essential to enable vulnerable people to protect themselves from infection, avoid delayed diagnosis and treatment, overcome barriers to adherence, and avert destitution. This paper analyses successful country proposals to the Global Fund to Fight AIDS, Tuberculosis and Malaria that include economic support in Rounds 7 and 10; 36 and 20 HIV and TB grants in Round 7 and 32 and 26, respectively, in Round 10. Of these, up to 84 percent included direct or indirect economic support for beneficiaries, although the amount constituted a very small proportion of the total grant. In TB grants, the objectives of economic support were generally clearly stated, and focused on mechanisms to improve treatment uptake and adherence, and the case was most clearly made for MDR-TB patients. In HIV grants, the objectives were much broader in scope, including mitigation of adverse economic and social effects of HIV and its treatment on both patients and families. The analysis shows that economic support is on the radar for countries developing Global Fund proposals, and a wide range of economic support activities are in place. In order to move forward in this area, the wealth of country experience that exists needs to be collated, assessed and disseminated. In addition to trials, operational research and programme evaluations, more precise guidance to countries is needed to inform evidence-based decision about activities that are cost-effective, affordable and feasible.
PLoS ONE 01/2014; 9(1):e86225. DOI:10.1371/journal.pone.0086225 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Given the spread of multidrug-resistant tuberculosis (MDR-TB), new therapies are urgently needed, including the repurposing of existing drugs. We aimed to assess key considerations for the clinical and programmatic use of clofazimine (Cfz), a riminophenazine with antimycobacterial activity currently used to treat leprosy.
Fixed and random effects meta-analysis of cohort studies and systematic review.
Electronic and manual searches were combined.
Observational studies on treatment of multidrug-resistant and extremely drug-resistant tuberculosis with Cfz or a Cfz-containing regimen, and published guidance and documents relating to cost and availability were eligible.
5 observational studies enrolled 861 patients, of which 602 received Cfz. The pooled proportion of adverse drug reactions requiring discontinuation of Cfz treatment was 0.1% (95% CI (0.0 to 0.6%)), and the median frequency of all adverse events was 5.1%. Cfz showed in vitro efficacy against Mycobacterium tuberculosis, and Cfz-containing regimens may have had a useful role in the treatment of patients with drug-resistant strains and who had limited alternative treatment options. However, Cfz uptake remains insufficient to meet global needs; there is only one internationally quality-assured manufacturer, which produces a limited quantity of the drug prioritised for treatment of leprosy, the only indication for which the drug is registered.
While the data were limited, Cfz was associated with a risk for adverse drug reactions comparable to that of first-line TB treatment, which could be reasonably managed under programmatic conditions. However, low market availability and high cost are important barriers to access to Cfz for patients with MDR-TB.
BMJ Open 01/2014; 4(1):e004143. DOI:10.1136/bmjopen-2013-004143 · 2.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A systematic review of the literature was conducted on the effectiveness of MDR-TB management. A meta-analysis of treatment outcomes of patients treated in hospitals versus ambulatory-based models was performed in accordance with PRISMA guidelines. The pooled treatment success rate was 66.4% (95% confidence interval [CI] 61.4-71.1%), with no statistical difference between ambulatory (65.5%; 55.1-74.6%) and hospital-based models (66.7%; 61.0-72.0%). The pooled death rate was 10.4% (6.3-16.5%), the pooled treatment failure rate was 9.5% (7.3-12.4%), and the defaulter rate was 14.3% (10.5-19.1%). None of the differences between the two models were statistically significant for any of the outcomes considered. This work improves the quality of the evidence available supporting the World Health Organizations (WHO) recommendation that patients be treated using mainly ambulatory care, conditional on infection control measures in the home and clinic, clinical condition of the patient, availability of treatment support to facilitate adherence to treatment, and provisions for backup facility to manage patients who need inpatient treatment care.
The American journal of tropical medicine and hygiene 08/2013; 89(2):271-80. DOI:10.4269/ajtmh.13-0004 · 2.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The prospects for global tuberculosis control in the near future will be determined by the effectiveness of the response of countries to their burden of multidrug-resistant (MDR; resistance to, at least, isoniazid and rifampicin) tuberculosis. During the 2009 World Health Assembly, countries committed to achieve universal access to MDR-tuberculosis care by 2015. We assessed the progress towards the 2015 targets achieved by countries accounting for 90% of the estimated MDR-tuberculosis cases in the world in 2011.
[Show abstract][Hide abstract] ABSTRACT: Despite decades of discussion of the role of informed consent in HIV testing and screening, there has been virtually no discussion of the role of informed consent in diagnosing TB. This article fills this gap by offering a comprehensive framework for analyzing the role of informed consent to diagnostic testing generally, and then applying that framework to the specific context of TB. It concludes that, in most situations, TB testing and screening does not require a specific informed consent process, but that patients should be notified about testing and given the opportunity to object. The article identifies limited circumstances, however, in which a specific consent process should be required.
European Respiratory Journal 05/2012; 39(5):1057-9. DOI:10.1183/09031936.00211611 · 7.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: For the first time in 40 years, a portfolio of promising new compounds for the treatment of tuberculosis is on the horizon. The introduction of new drugs in combination treatment for all forms of tuberculosis raises several issues related to patients' access to novel treatments, programmatic feasibility, cost effectiveness, and implications for monitoring and surveillance, particularly with regard to the development of drug resistance. Particular attention should be given to the identification of optimal drug combination(s) for the treatment of all forms of tuberculosis, particularly in high-risk and vulnerable groups, such as human immunodeficiency virus-coinfected persons and children, and to the rational use of new drugs. Addressing these issues adequately requires the establishment of clear guidelines to assist countries in the development of policies for the proper use of tuberculosis drugs in a way that guarantees access to best treatments for all those in need and avoids inappropriate use of new drugs. After a description of these various challenges, we present activities that will be carried out by the World Health Organization in collaboration with key stakeholders for the development of policy guidelines for optimal treatment of tuberculosis.
The Journal of Infectious Diseases 03/2012; 205 Suppl 2(suppl 2):S241-9. DOI:10.1093/infdis/jis034 · 6.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Multidrug-resistant tuberculosis programs in DOTS-Plus pilot sites in five countries.
To calculate sputum conversion time and its relationship to treatment outcome, document the frequency of culture reversions and examine concordance of smear and culture to assess the potential consequences of monitoring by smear microscopy alone.
Retrospective cohort analysis of 1926 patients receiving individualized, second-line therapy.
Among 1385 sputum culture-positive cases at baseline, 1146 (83%) experienced at least one culture conversion during treatment. Conversion, however, was not sustained in all patients: 201 (15%) experienced initial culture conversion and at least one subsequent culture reversion to positive; 1064 (77%) achieved sustained culture conversion. Median time to culture conversion was 3 months. Among 206 patients whose nal conversion occurred 7-18 months after the initiation of therapy, 71% were cured or had completed treatment.
Prolonged treatment for patients with delayed conversion may be beneficial, as 71% of late converters still achieved cure or completed treatment. This has implications for programs with de ned end points for treatment failure. The interval between rst and nal conversion among patients whose initial con- version is not sustained raises concern with respect to the ongoing debate regarding duration of treatment and the definition of cure.
The International Journal of Tuberculosis and Lung Disease 10/2011; 15(10):1315-22. DOI:10.5588/ijtld.10.0221 · 2.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The production of guidelines for the management of drug-resistant tuberculosis (TB) fits the mandate of the World Health Organization (WHO) to support countries in the reinforcement of patient care. WHO commissioned external reviews to summarise evidence on priority questions regarding case-finding, treatment regimens for multidrug-resistant TB (MDR-TB), monitoring the response to MDR-TB treatment, and models of care. A multidisciplinary expert panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. The recommendations support the wider use of rapid drug susceptibility testing for isoniazid and rifampicin or rifampicin alone using molecular techniques. Monitoring by sputum culture is important for early detection of failure during treatment. Regimens lasting ≥ 20 months and containing pyrazinamide, a fluoroquinolone, a second-line injectable drug, ethionamide (or prothionamide), and either cycloserine or p-aminosalicylic acid are recommended. The guidelines promote the early use of antiretroviral agents for TB patients with HIV on second-line drug regimens. Systems that primarily employ ambulatory models of care are recommended over others based mainly on hospitalisation. Scientific and medical associations should promote the recommendations among practitioners and public health decision makers involved in MDR-TB care. Controlled trials are needed to improve the quality of existing evidence, particularly on the optimal composition and duration of MDR-TB treatment regimens.
European Respiratory Journal 08/2011; 38(3):516-28. DOI:10.1183/09031936.00073611 · 7.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Improved tuberculosis (TB) diagnosis and treatment through the DOTS and Stop TB strategies have saved millions of lives; however, their impact on TB incidence has been disappointing and the scale of the epidemic remains overwhelming. To reduce the incidence of TB, the drivers of the epidemic and social determinants of TB need to be addressed. These include co-morbidities and substance use and, moreover, the social and economic conditions that determine both the course of the TB epidemic and exposure to these risk factors. Doing so builds on the history of TB prevention and treatment during the public health revolution that resulted in a dramatic reduction in incidence in many countries. Addressing the social determinants is also imperative to address pervasive inequities in the incidence, mortality and morbidity of TB between different population groups, including in the performance of health systems in delivering diagnostic and treatment interventions, and in the financial consequences of people seeking care. Action on the social determinants can be categorised in terms of health-sector interventions, intersectoral policies impacting across society, and measurement and research to better understand inequities and links between TB and other factors. TB programmes cannot carry out these actions alone; however, they can make important contributions in the delivery of interventions and in advocating and negotiating for intersectoral efforts. The considerable progress seen in the clinical care of TB needs to be sustained; however, the attainment of TB targets, including elimination by 2050, will require expansion of the lens of TB control efforts beyond 'business as usual' to address the social determinants of the disease.
The International Journal of Tuberculosis and Lung Disease 06/2011; 15 Suppl 2(Supplement 2):S30-6. DOI:10.5588/ijtld.10.0691 · 2.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To quantify the impact of cash transfer and microfinance interventions on a selected list of tuberculosis (TB) risk factors and assess their potential role in supporting TB control.
Published and unpublished references identified from clinical and social electronic databases, grey literature and web sites.
Eligible interventions had to be conducted in middle- or low-income countries and document an impact evaluation on any of the following outcomes: 1) TB or other respiratory infections; 2) household socio-economic position; and 3) factors mediating the association between low household socio-economic position and TB, including inadequate health-seeking behaviours, food insecurity and biological TB risk factors such as human immunodeficiency virus (HIV) and adult malnutrition. Interventions targeting special populations were excluded.
Fifteen cash transfer schemes (four unconditional and 11 conditional) and seven microfinance programmes met the eligibility criteria. No intervention addressed TB or any other respiratory infection. Of 11 cash transfer and four microfinance interventions, respectively seven and four reported a positive impact on indicators of economic well-being. A positive impact on household food security was documented in respectively eight of nine and three of five cash transfer and microfinance interventions. Improved health care access was documented respectively in 10 of 12 cash transfer and four of five microfinance interventions. The only intervention evaluating impact on HIV incidence was a microfinance project that found no effect. No cash transfer or microfinance interventions had an impact on adult malnutrition.
Cash transfer and microfinance interventions can positively impact TB risk factors. Evaluation studies are urgently needed to assess the impact of these social protection interventions on actual TB indicators.
The International Journal of Tuberculosis and Lung Disease 06/2011; 15 Suppl 2(6):S37-49. DOI:10.5588/ijtld.10.0438 · 2.32 Impact Factor