Léopold Blanc

WHO guidelines for the programmatic management of drug-resistant tuberculosis: 2011 update

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.

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

BACKGROUND 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. METHODS 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. FINDINGS 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. INTERPRETATION 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.

Tuberculosis and noncommunicable diseases: neglected links and missed opportunities

Globally, the incidence of tuberculosis (TB) is declining very slowly, and the noncommunicable disease (NCD) burden for many countries is steadily increasing. Several NCDs, such as diabetes mellitus, alcohol use disorders and smoking-related conditions, are responsible for a significant proportion of TB cases globally, and in the European region, represent a larger attributable fraction for TB disease than HIV. Concrete steps are needed to address NCDs and their risk factors. We reviewed published studies involving TB and NCDs, and present a review and discussion of how they are linked, the implications for case detection and management, and how prevention efforts may be strengthened by integration of services. These NCDs put patients at increased risk for developing TB and at risk for poor treatment outcomes. However, they also present an opportunity to provide better care through increased case-detection activities, improved clinical management and better access to care for both TB and NCDs. Hastening the global decline in TB incidence may be assisted by strengthening these types of activities.

Tuberculosis and non-communicable diseases: neglected links, missed opportunities

Globally, the incidence of tuberculosis (TB) is declining very slowly, and the noncommunicable disease (NCD) burden for many countries is steadily increasing. Several NCDs, such as diabetes mellitus, alcohol use disorders and smoking-related conditions, are responsible for a significant proportion of TB cases globally, and in the European region, represent a larger attributable fraction for TB disease than HIV. Concrete steps are needed to address NCDs and their risk factors. We reviewed published studies involving TB and NCDs, and present a review and discussion of how they are linked, the implications for case detection and management, and how prevention efforts may be strengthened by integration of services. These NCDs put patients at increased risk for developing TB and at risk for poor treatment outcomes. However, they also present an opportunity to provide better care through increased case-detection activities, improved clinical management and better access to care for both TB and NCDs. Hastening the global decline in TB incidence may be assisted by strengthening these types of activities.

Implementation of isoniazid preventive therapy for people living with HIV worldwide: barriers and solutions.

Tuberculosis (TB) is the most frequent life-threatening opportunistic disease in people living with HIV (PLHIV) in the first 3 months of antiretroviral treatment (ART), in both industrialized and resource-constrained settings [1,2]. ART significantly but not entirely reduces the risk of TB disease [3]. It is also associated with significantly increased mortality both before and during ART [4–6]. Morbidity and mortality from drug-sensitive and drug-resistant TB among PLHIV are unacceptably high [7,8]. For all these reasons regular screening of all PLHIV for active TB disease and provision of either treatment for active disease or preventive therapy, and the provision of earlier ART [9] along with other measures to minimise TB transmission are essential.

The health workforce crisis in TB control: a report from high-burden countries

BackgroundHuman resources (HR) constraints have been reported as one of the main barriers to achieving the 2005 global tuberculosis (TB) control targets in 18 of the 22 TB high-burden countries (HBCs); consequently we try to assess the current HR available for TB control in HBCs.MethodsA standard questionnaire designed to collect information on staff numbers, skills, training activities and current staff shortages at different health service levels was sent to national TB control programme managers in all HBCs.ResultsNineteen HBCs (86%) replied, and 17 (77%) followed the questionnaire format to provide data. Complete information on staff numbers at all service levels was available from nine countries and data on skill levels and training were complete in six countries. Data showed considerable variations in staff numbers, proportions of trained staff, length of courses and quality of training activities. Eleven HBCs had developed training materials, many used implementation guidelines for training and only three used participatory educational methods. Two countries reported shortages of staff at district health facility level, whereas 14 reported shortages at central level. There was no apparent association between reported staff numbers (and skills) and the countrys TB burden or current case detection rates (CDR).ConclusionThere were few readily available data on HR for TB control in HBCs, particularly in the larger ones. The great variations in staff numbers and the poor association between information on workforce, proportion of trained staff, and length and quality of courses suggested a lack of valid information and/or poor data reliability. There is urgent need to support HBCs to develop a comprehensive HR strategy involving short-term and long-term HR development plans and strengthening their HR planning and management capabilities.

Global Policy Review of Antiretroviral Therapy Eligibility Criteria for Treatment and Prevention of HIV and Tuberculosis in Adults, Pregnant Women, and Serodiscordant Couples

Objective:This article reviews the antiretroviral therapy (ART) initiation criteria from national treatment guidelines for 70 countries and determines the extent of consistency with the current World Health Organization (WHO) recommendations. Methods:Published ART guidelines were collected from the Internet, databases, and WHO staff. ART eligibility criteria for asymptomatic people, pregnant women, people with HIV-associated tuberculosis, serodiscordant couples, injecting drug users, men who have sex with men, and sex workers were abstracted from them. Multiple regression analysis was used to determine the relation between ART eligibility criteria, ART coverage, and various population characteristics and policy interventions. Results:Of the 70 countries, 42 (60%) follow WHO’s ART guidelines for asymptomatic people and 31 (44%) for pregnant women, recommending ART at CD4 count of ⩽350 cells/mm3. Twenty-three (33%) countries recommend ART for people with HIV-associated tuberculosis irrespective of CD4 count. Nineteen countries are also recommending or considering earlier ART above CD4 count ⩽350 cell/mm3 for asymptomatic people, pregnant women, and/or serodiscordant couples. Multiple linear regression analysis shows that HIV prevalence, year of publication of guidelines, and HIV expenditure are significantly associated with published ART eligibility criteria. On average, the ART coverage is similar irrespective of published guidelines being consistent with the WHO recommendation (P < 0.53). Conclusions:Published guidelines from a significant number of countries are not following WHO recommendations. Although published guidelines may not reflect practice, it is important to adapt recommendations and services quickly to reflect the emerging science on the health and prevention benefits of earlier access to ART.

Tuberculosis and air travel: Who guidance in the era of drug-resistant TB

Air travel provides opportunities for infectious diseases to spread rapidly between countries and continents. There may be a potential risk of transmission during the flight, notably with airborne and droplet-borne respiratory infections. Seven episodes of potential transmission of TB infection during air travel reported in 1992--1994 caused widespread concern. Contact investigations revealed evidence of transmission of infection in two instances but active TB disease was not found in any of the infected individuals, or in subsequently published cases. In recent years, multidrug-resistant TB (MDR-TB) has become an increasingly important public health problem in many countries, exacerbated by the emergence of extensively drug-resistant TB (XDR-TB). The potential risk of transmission of particularly dangerous forms of TB requires renewed vigilance. The revised International Health Regulations (1995) include new provisions which are relevant to the transmission of TB on aircraft. WHO published a second edition of Tuberculosis and air travel: guidelines for prevention and control in 2006, providing updated information and specific guidance for passengers and crew, physicians, public health authorities and airline companies. Following several recent incidents involving MDR-TB and XDR-TB in airline passengers, the 2006 recommendations will be amplified in the light of experience gained and the evolving epidemiological situation.

Modernizing surveillance of antituberculosis drug resistance: from special surveys to routine testing.

Availability of new diagnostic tools and global commitment towards universal access to tuberculosis care will accelerate capacity of resource-limited countries to monitor anti-tuberculosis drug resistance. Special surveys will be replaced by routine surveillance of drug resistance linked to patient care.

Reply to 'Addressing smoking cessation in tuberculosis control'

We welcome the commentary “Addressing Smoking Cessation in Tuberculosis Control” responding to the Bulletin theme issue on tuberculosis (May 2007), and thank the authors for raising this important issue. If action is not taken to curb the spread of tobacco use, annual deaths are expected to reach 8.3 million by 2030, of which more than 80% will be in developing countries.1 Smoking globally is about four times more common among men than women. However, trends are changing, with increasing levels among women, and girls are smoking almost as much as boys in many settings.2 In addition, girls and boys use non-cigarette tobacco products such as chewing tobacco, bidis and water pipes at similar rates. Many of the countries with increasing tobacco consumption are those with a high burden of TB. Core TB control components, as advocated in the Stop TB Strategy, are intended to break the chain of mycobacterial transmission by ensuring early diagnosis and effective treatment of TB patients. However, over the past decades, global TB control strategies have paid less attention to the relative importance of different determinants and risk factors for TB, such as smoking, malnutrition, diabetes, crowding and indoor air pollution. There is a clear need to address these risk factors to reduce people’s vulnerability to TB infection and disease. We are pursuing work on these risk factors in a project linked to the Commission on Social Determinants of Health. Such additional approaches to TB control are necessary to significantly curb the epidemic and will contribute to reaching the 2015 Millennium Development Goal related to TB control. Preventing smoking or encouraging people to quit can substantially reduce both the incidence of clinical tuberculosis and tuberculosis deaths.3 At the same time, it is crucial to strengthen the role of health professionals in tobacco control as promoted in Articles 12 and 14 of the WHO Framework Convention on Tobacco Control.4 Physicians and public health workers should energetically apply anti-smoking interventions in populations with high levels of subclinical tuberculosis infection. Since exposure to environmental tobacco smoke at home or at work is also a risk for those with compromised respiratory systems, including TB patients, it is crucial to effectively implement the WHO Framework Convention’s Article 8 on protection from exposure to tobacco smoke. Since 2005, WHO has been exploring collaborative activities between TB control and tobacco control efforts. As a first step, the effects of smoking (active smoking and exposure to tobacco smoke) on TB were investigated in a systematic review of the literature jointly undertaken by WHO and the International Union Against Tuberculosis and Lung Diseases. The specific effects studied included those on TB infection and disease, recurrent TB, TB characteristics and case management (delay in seeking care, default, smear conversion, disease severity, acquired drug resistance) and mortality during and after TB treatment. On the basis of strict and standardized criteria, 42 articles containing 50 studies for data extraction were selected for final inclusion in the meta-analysis. The meta-analysis showed that smoking and exposure to tobacco smoke have a significant impact on susceptibility to TB infection, progression to TB disease and treatment outcomes. The evidence was rated as strong for an association between exposure to tobacco smoke and TB disease, moderate for the association between tobacco use and recurrent TB disease, limited for the association between exposure to tobacco smoke and TB infection, and between tobacco use and TB mortality (both for TB mortality and for TB and death during and after treatment). Limited data supported an association between tobacco use and patient delay in seeking care, default, slower smear conversion and greater severity of disease or drug-resistant tuberculosis. The effects appeared to be independent of the effects of alcohol use, socio-economic status and other potential confounders. Furthermore, an analysis of the impact of smoking on the global TB epidemic is in progress. Preliminary analysis suggests that a significant proportion, probably more than 20%, of the global TB burden may be attributable to smoking, and this proportion will increase if smoking prevalence increases, thus undermining TB control efforts. As a follow-up to the systematic review, in the fall of 2006 WHO developed a policy paper on the integration of TB and tobacco control activities into primary care services using the Practical Approach to Lung Health (PAL), a component of the Stop TB strategy. PAL was chosen because tobacco smoke has a negative impact on all patients with respiratory symptoms seeking care at primary care services, including those with TB. The policy paper calls upon primary care workers to: (i) identify smokers; (ii) provide behavioural therapy (counselling) for smoking cessation and where available pharmacological interventions, including nicotine replacement therapy and non-nicotine medications; (iii) refer smokers to specialist services for intensive cessation therapy when required and where possible; and (iv) deliver primary care services in smoke-free environments. To this extent, health ministries are encouraged to establish a coordination mechanism with representatives from both the national TB control programmes and the national tobacco control units. Such coordinating bodies have the responsibility of developing a national policy and action plan for the implementation of joint activities including developing health education materials, training human resources, establishing a structure to supervise tobacco control activities among respiratory patients and establishing a mechanism to monitor and evaluate the impact of integrated services. This collaborative approach is expected to (i) improve the outcome of TB treatment and reduce the infectivity period limiting TB transmission to contacts; (ii) prevent smoking and promote smoking cessation among all respiratory patients who seek primary care, including those with TB; and, (iii) demonstrate that tobacco control efforts can be expanded through activities related to the Stop TB strategy. If tobacco control activities are successfully implemented at primary care services through the Stop TB strategy and PAL, they can gradually be extended to other patients under other national programmes such as maternal health, cardiovascular diseases, cancer and diabetes control until these activities reach all persons attending health units for curative or preventive care. WHO plans to scale up the implementation of activities as part of its medium-term strategic plan approved by the World Health Assembly in May 2007. The policy paper is due to be published during 2007. In addition, WHO is implementing the collaborative approach through a pilot study in Nepal that started in June 2007. Nepal, a party to the Framework Convention, was invited to implement a pilot test because of its relatively high smoking prevalence and TB burden, and because PAL activities have already begun in its primary care services. Other countries will start similar pilot studies in the near future. WHO is encouraging countries to express interest in this approach, which targets two of the world’s key public health priorities. ■