International Standards for Tuberculosis Care: revisiting the cornerstones of tuberculosis care and control

Special Report International Standards for Tuberculosis Care: revisiting the cornerstones of tuberculosis care and control Elizabeth Fair, Philip C Hopewell and Madhukar Pai CONTENTS Tuberculosis remains a global challenge International Standards for Tuberculosis Care Differing contexts, similar challenges, a shared approach Information resources Key issues References Affiliations Tuberculosis (TB) remains an enormous global health problem. There are 8 9 million new cases and 2 million deaths from TB annually. Despite the overwhelming burden of disease, the basic principles of care for persons with, or suspected of having, TB are the same worldwide: a diagnosis should be established promptly and accurately, standardized treatment regimens of proven efficacy should be used together with appropriate treatment support and supervision, the response to treatment should be monitored, and the essential public health responsibilities must be carried out. As an approach to improving the care of patients with TB, an evidence-based document, the International Standards for Tuberculosis Care (ISTC) was developed and has been endorsed by more than 30 international and national agencies. This special report introduces the ISTC and discusses the fact that accurate diagnosis and effective treatment are not only essential for good patient care, they are the key elements in the public health response to TB and are the cornerstone of TB control. With the recent emergence of extensively drug-resistant TB, there is an urgent need to ensure globally that standards of TB care are based on rigorous scientific findings, are clear and well understood, and are accessible to and applied by all types of healthcare providers in all corners of the world. Author for correspondence McGill University, Department of Epidemiology, Biostatistics and Occupational Health, 1020 Pine Avenue West, Montreal, Quebec, H3A 1A2, Canada Tel.: +1 514 398 5422 Fax: +1 514 398 4503 madhukar.pai@mcgill.ca KEYWORDS guidelines, recommendations, standards, tuberculosis Expert Rev. Anti Infect. Ther. 5(1), 61 65 (2007) Tuberculosis remains a global challenge Although in the past 10 years there has been substantial progress in the development and implementation of the strategies necessary for effective tuberculosis control, the disease remains an enormous and growing global health problem [1 4]. A third of the world s population is infected with Mycobacterium tuberculosis, with 95% of cases occuring in developing countries [3]. In 2003, there were an estimated 8.8 million new cases of tuberculosis, of which 3.9 million were sputum smearpositive and, thus, highly infectious [1,2]. The number of tuberculosis cases that occur in the world each year is still growing, although the rate of increase is slowing. In the African region of the WHO, the tuberculosis case rate continues to increase, owing to both the epidemic of HIV infection in sub-saharan countries and the poor or absent primary-care services throughout the region [1,2]. In many other countries, owing to incomplete application of effective care and control measures, tuberculosis case rates are either stagnant or decreasing more slowly than expected. The failure to bring about a more rapid reduction in tuberculosis incidence is related, at least in part, to a failure to fully engage all medical care providers in the delivery of high-quality care, in coordination with local and national tuberculosis control programs. In many parts of the world, private practitioners are involved in the diagnosis and treatment of tuberculosis [5 8]. Traditional healers, general, specialist and academic physicians, nurses, unlicensed practitioners, physicians in private practice, practitioners of alternative medicine and community organizations, www.future-drugs.com 10.1586/14787210.5.1.61 2007 Future Drugs Ltd ISSN 1478-7210 61

Fair, Hopewell & Pai among others, all play roles in tuberculosis care and, therefore, in tuberculosis control. Little is known regarding the adequacy of care delivered by private providers; however, available data suggest that, in many instances, the services are of poor quality. A global situation assessment reported by the WHO, as well as other studies conducted during the past 10 15 years, demonstrates that clinicians who work in the private healthcare sector often deviate from standard, internationally recommended tuberculosis management practices [6,7]. These deviations include: under-utilization of sputum microscopy for diagnosis, generally associated with over-reliance on radiography; use of nonrecommended drug regimens, with incorrect combinations of drugs and mistakes in both drug dosage and duration of treatment; and failure to supervise and assure adherence to treatment [6,7,9 15]. Anecdotal evidence also suggests that there is an over-reliance on poorly validated or inappropriate diagnostic tests, such as serological assays, often in preference to conventional bacteriological evaluations. Together, these findings highlight flaws in healthcare practices that lead to substandard tuberculosis care for populations that are most vulnerable to the disease and are least able to bear the consequences of such systemic failures. International Standards for Tuberculosis Care The basic principles of care for individuals with, or suspected of having, tuberculosis are the same worldwide: a diagnosis should be established promptly and accurately; standardized treatment regimens of proven efficacy should be used, together with appropriate treatment support and supervision; the response to treatment should be monitored; and the essential public health responsibilities must be carried out. Accurate diagnosis and effective treatment are not only essential for good patient care, they are the key elements in the public health response to tuberculosis and are the cornerstone of tuberculosis control. Substandard care will result in poor patient outcomes, continued infectiousness with transmission of M. tuberculosis to others and generation and propagation of drug resistance. As an approach to improving the care of patients with tuberculosis, the principles noted above were used as the foundation for a set of evidence-based standards, the International Standards for Tuberculosis Care (ISTC), which was released on World TB Day 2006 [16] and subsequently published in a condensed form in Lancet Infectious Diseases [17]. Since its release, the ISTC has been endorsed by more than 30 international and national agencies and organizations, including the WHO, the Stop TB Partnership, the International Union against TB and Lung Disease (IUATLD), the American Thoracic Society (ATS), the CDC, the International Council of Nurses, the Canadian Tuberculosis Committee and the World Care Council. The ISTC was developed by examining existing evidence and, where evidence was lacking, conducting rigorous systematic reviews. The result was agreement on a group of 17 standards: six addressing diagnosis, nine addressing treatment and two addressing public health responsibilities (TABLE 1). The ISTC as a whole is not meant to be a guidance document for how tuberculosis care should be provided but rather the principles and foundation on which guidelines can be based. The document emphasizes that any clinician who provides services for tuberculosis is assuming an important public health function. Differing contexts, similar challenges, a shared approach There is a vast spectrum of diagnostic, treatment and public health practices involved in tuberculosis care. The ISTC presents the essential elements of tuberculosis care and, consequently, should be viewed as a platform on which additional elements of care can be based. In many geographical areas, the available facilities and resources exceed those required to comply with the ISTC. However, even in these areas, certain elements of the standards may not be implemented. This is particularly true with regards to treatment supervision and the application of a true patient-centered approach, as specified in the ISTC. Conversely, healthcare providers from settings in which there is no regular access to vital services, such as chest radiographic examinations or drug-sensitivity testing, will recognize that they are far from able to achieve the practices recommended in the ISTC. For example, in a rural clinic in Tanzania, basic diagnostic techniques, such as sputum smear microscopy, may be a challenge owing to lack of a microscope, lack of stain or slides, or lack of electricity. In the context of such diversity, the ISTC can function as a template or checklist against which providers and programs can assess the realities of their particular situations and determine what is needed to bring practices up to the level of those specified by the ISTC. In both areas with adequate resources and in resource-constrained settings, the ISTC provides a starting point to determine what is needed a tool for a situational analysis that can then be used to guide pursuit of improved tuberculosis care. Using this standardized situational analysis as a point of departure, specific plans can be developed that, for example, may be focused on increasing funding, developing new systems or altering approaches so as to be consistent with the ISTC, with the goal of providing high-quality tuberculosis care that meets the needs of all patients. In the last few months, a new threat has been identified: extensively drug-resistant tuberculosis (XDR-TB) [18]. Currently, the WHO defines XDR-TB as tuberculosis resistant to at least rifampicin and isoniazid from among the first-line antituberculosis drugs (which is the definition of multidrug resistant [MDR]-TB) in addition to any fluoroquinolones, and to at least one of three injectable second-line antituberculosis drugs used in tuberculosis treatment (capreomycin, kanamicin and amikacin). What is evident is that had care of the quality specified in the ISTC been applied in the areas where XDR-TB is emerging, this disaster would not have happened. The emergence of XDR-TB is a sign that proper standards of tuberculosis care are far from being applied universally [19]. It is worth looking back at what the tuberculosis community learned from the experience of New York City (NY, USA) just over 10 years ago. In the early 1990s, there was a significant 62 Expert Rev. Anti Infect. Ther. 5(1), (2007)

International Standards for Tuberculosis Care Table 1. International Standards for Tuberculosis Care. Standards for diagnosis Standard 1 All persons with otherwise unexplained productive cough lasting 2 3 weeks should be evaluated for TB Standard 2 Standard 3 Standard 4 Standard 5 Standard 6 All patients (adults, adolescents and children who are capable of producing sputum) suspected of having pulmonary TB should have at least two, and preferably three, sputum specimens obtained for microscopic examination. When possible, at least one early morning specimen should be obtained For all patients (adults, adolescents and children) suspected of having extrapulmonary TB, appropriate specimens from the suspected sites of involvement should be obtained for microscopy and, where facilities and resources are available, for culture and histopathological examination All persons with chest radiographical findings suggestive of TB should have sputum specimens submitted for microbiological examination The diagnosis of sputum smear-negative pulmonary TB should be based on the following criteria: at least three negative sputum smears (including at least one early morning specimen); chest radiography findings consistent with TB; and lack of response to a trial of broad-spectrum antimicrobial agents. (Since fluoroquinolones are active against Mycobacterium tuberculosis complex and, thus, may cause transient improvement in persons with TB, they should be avoided). For such patients, if facilities are available, sputum cultures should be obtained. In individuals with known or suspected HIV infection, the diagnostic evaluation should be expedited The diagnosis of intrathoracic (i.e., pulmonary, pleural and mediastinal or hilar lymph node) TB in symptomatic children with negative sputum smears should be based on the finding of chest radiographical abnormalities consistent with TB and either a history of exposure to an infectious case or evidence of TB infection (positive tuberculin skin test or interferon-γ release assay). For such patients, if facilities for culture are available, sputum specimens should be obtained (by expectoration, gastric washings or induced sputum) for culture Standards for treatment Standard 7 Any practitioner treating a patient for TB is assuming an important public health responsibility. To fulfill this responsibility, the practitioner must not only prescribe an appropriate regimen, but also be capable of assessing the adherence of the patient to the regimen and addressing poor adherence when it occurs. By so doing, the provider will be able to ensure adherence to the regimen until treatment is completed Standard 8 Standard 9 Standard 10 Standard 11 All patients (including those with HIV infection) who have not been treated previously should receive an internationally accepted first-line treatment regimen using drugs of known bioavailability. The initial phase should consist of 2 months of isoniazid, rifampicin, pyrazinamide and ethambutol. The preferred continuation phase consists of isoniazid and rifampicin administered for 4 months. Isoniazid and ethambutol administered for 6 months is an alternative continuation-phase regimen that may be used when adherence cannot be assessed, but it is associated with a higher rate of failure and relapse, especially in patients with HIV infection. The doses of anti-tb drugs used should conform to international recommendations. Fixed dose combinations of two (isoniazid and rifampicin), three (isoniazid, rifampicin and pyrazinamide) and four (isoniazid, rifampicin, pyrazinamide and ethambutol) drugs are highly recommended, especially when medication ingestion is not observed To foster and assess adherence, a patient-centered approach to the administration of drug treatment, based on the patient s needs and mutual respect between the patient and the provider, should be developed for all patients. Supervision and support should be sex sensitive and age specific and should draw on the full range of recommended interventions and available support services, including patient counseling and education. A central element of the patient-centered strategy is the use of measures to assess and promote adherence to the treatment regimen and to address poor adherence when it occurs. These measures should be tailored to the individual patient s circumstances and be mutually acceptable to the patient and the provider. Such measures may include direct observation of medication ingestion (DOT) by a treatment supporter who is acceptable and accountable to the patient and the health system All patients should be monitored for response to therapy, best judged in patients with pulmonary TB by follow-up sputum microscopy (two specimens) at least at the time of completion of the initial phase of treatment (2 months), at 5 months and at the end of treatment. Patients who have positive smears during the 5th month of treatment should be considered as treatment failures and have therapy modified appropriately (see standards 14 and 15). In patients with extrapulmonary TB and in children, the response to treatment is best assessed clinically. Follow-up radiographical examinations are usually unnecessary and may be misleading A written record of all medications given, bacteriological response and adverse reactions should be maintained for all patients Taken from [16,17]. DOT: Directly observed therapy; MDR: Multidrug resistant; TB: Tuberculosis. www.future-drugs.com 63

Fair, Hopewell & Pai Table 1. International Standards for Tuberculosis Care (cont.). Standard 12 Standard 13 Standard 14 Standard 15 In areas with a high prevalence of HIV infection in the general population and where TB and HIV infection are likely to coexist, HIV counseling and testing are indicated for all TB patients as part of their routine management. In areas with lower prevalence rates of HIV, HIV counseling and testing are indicated for TB patients with symptoms and/or signs of HIV-related conditions and in TB patients with a history suggestive of high risk of HIV exposure All patients with TB and HIV infection should be evaluated to determine whether antiretroviral therapy is indicated during the course of treatment for TB. Appropriate arrangements for access to antiretroviral drugs should be made for patients who meet indications for treatment. Given the complexity of co-administration of anti-tb treatment and antiretroviral therapy, consultation with a physician who is expert in this area is recommended before initiation of concurrent treatment for tuberculosis and HIV infection, regardless of which disease appeared first. However, initiation of treatment for TB should not be delayed. Patients with TB and HIV infection should also receive cotrimoxazole as prophylaxis for other infections An assessment of the likelihood of drug resistance, based on history of prior treatment, exposure to a possible source case having drug-resistant organisms, and the community prevalence of drug resistance should be obtained for all patients. Patients who fail treatment and chronic cases should always be assessed for possible drug resistance. For patients in whom drug resistance is considered to be likely, culture and drug susceptibility testing for isoniazid, rifampicin and ethambutol should be performed promptly Patients with TB caused by drug-resistant (especially MDR) organisms should be treated with specialized regimens containing second line anti-tb drugs. At least four drugs to which the organisms are known or presumed to be susceptible should be used and treatment should be given for 18 months. Patient-centered measures are required to ensure adherence. Consultation with a provider experienced in treatment of patients with MDR-TB should be obtained Standards for public health responsibilities Standard 16 All providers of care for patients with TB should ensure that individuals (especially children aged <5 years and individuals with HIV infection) who are in close contact with patients who have infectious TB are evaluated and managed in line with international recommendations. Children aged below 5 years and individuals with HIV infection who have been in contact with an infectious case should be evaluated for both latent infection with M. tuberculosis and for active TB Standard 17 All providers must report both new and retreatment TB cases and their treatment outcomes to local public health authorities, in conformance with applicable legal requirements and policies Taken from [16,17]. DOT: Directly observed therapy; MDR: Multidrug resistant; TB: Tuberculosis. resurgence of tuberculosis and the emergence of a highly resistant MDR-TB strain (the W strain) of M. tuberculosis in New York City. As the incidence of tuberculosis had declined over the years, so had the investment in the programs that controlled the disease. This gradual divestment in public health, coupled with the HIV epidemic, led to a resurgence of tuberculosis. By 1992, the number of cases had nearly tripled in 15 years [20]. In the first quarter of 1991, New York City, comprising only 3% of the nation s population, accounted for 61% of the MDR-TB cases in the USA [21]. In some neighborhoods of the city, incidence rates were estimated to be 222 per 100,000, greater than in many developing countries [22]. When these trends were identified, there was great alarm in the public health community and attention was refocused on the basic standards of care for tuberculosis. Within 2 years, there was a dramatic decrease in the disease. Incidence rates were cut by 20%, and there was interruption of ongoing transmission of tuberculosis. Simple programmatic interventions and planning, such as directly observed therapy, improved case detection and infection control, and broader use of drug susceptibility testing were identified as having contributed to reversing the trend. The costs borne by the public health system in New York City were extraordinary, yet the primary interventions relatively simple. Many of these interventions are the tenets of the ISTC. As we face this new threat of XDR-TB, it is imperative to revisit the cornerstones of tuberculosis care. Without diligent attention, we may see further spread of XDR-TB and this will become a serious challenge to health systems, regardless of the setting and resources. Now more than ever, we need to ensure globally that our standards of care are based on rigorous scientific findings, are clear and well understood, and are accessible to and applied by all types of health care providers public, private, certified and nontraditional in all corners of the world. Ultimately, new drugs and new diagnostics are needed, but while these work their way through the pipeline it is imperative to universally implement the essential standards of tuberculosis care. Information resources The International Standards for Tuberculosis Care report can be freely downloaded from several websites: Stop TB www.stoptb.org/resource_center/assets/documents/istc_ report.pdf The WHO www.who.int/tb/publications/2006/istc/en/index.html The abbreviated publication [17] can be downloaded freely from the Lancet website www.thelancet.com/journals/laninf 64 Expert Rev. Anti Infect. Ther. 5(1), (2007)

International Standards for Tuberculosis Care Key issues The basic principles of care for individuals with, or suspected of having, tuberculosis (TB) are the same worldwide. Accurate diagnosis and effective treatment of TB are essential for good patient care, and are key elements in the public health response to and control of TB. Incomplete and/or inadequate TB care poses a threat to the continued spread of the disease and the propagation of drug-resistant TB. There is considerable evidence that quality of TB care varies widely, and substandard care is widespread, especially in the private healthcare sector in many developing countries. As an approach to engaging all healthcare providers, and improving the care of patients with TB, a set of evidence-based standards, the International Standards for Tuberculosis Care (ISTC), were developed and released on World TB Day 2006. To improve the quality of TB care, the ISTC should be understandable, accessible and universally applied by all care providers public, private, certified and nontraditional. References 1 WHO, Global Tuberculosis Control. Surveillance, planning, financing. WHO Report. WHO, Geneva, 1 247 (2005). 2 Corbett EL, Watt CJ, Walker N et al. The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Arch. Intern. Med. 163(9), 1009 1021 (2003). 3 Dye C, Scheele S, Dolin P, Pathania V, Raviglione MC. Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project. JAMA 282(7), 677 686 (1999). 4 Dye C, Watt CJ, Bleed DM, Hosseini SM, Raviglione MC. Evolution of tuberculosis control and prospects for reducing tuberculosis incidence, prevalence, and deaths globally. JAMA 293(22), 2767 2775 (2005). 5 Uplekar M. Involving private health care providers in delivery of TB care: global strategy. Tuberculosis (Edinb.) 83(1 3), 156 164 (2003). 6 Uplekar M, Pathania V, Raviglione M. Private practitioners and public health: weak links in tuberculosis control. Lancet 358(9285), 912 916 (2001). 7 WHO. Involving private practitioners in tuberculosis control: issues, interventions, and emerging policy framework. WHO, Geneva, Switzerland 1 81 (2001). 8 WHO. Public-private mix for DOTS. Practical tools to help implementation. WHO, Geneva, Switzerland (2003). 9 Lonnroth K, Thuong LM, Linh PD, Diwan VK. Delay and discontinuity a survey of TB patients search of a diagnosis in a diversified health care system. Int. J. Tuberc. Lung Dis. 3(11), 992 1000 (1999). 10 Olle-Goig JE, Cullity JE, Vargas R. A survey of prescribing patterns for tuberculosis treatment amongst doctors in a Bolivian city. Int. J. Tuberc. Lung Dis. 3(1), 74 78 (1999). 11 Prasad R, Nautiyal RG, Mukherji PK, Jain A, Singh K, Ahuja RC.. Diagnostic evaluation of pulmonary tuberculosis: what do doctors of modern medicine do in India? Int. J. Tuberc. Lung Dis. 7(1), 52 57 (2003). 12 Shah SK, Sadiq H, Khalil M et al. Do private doctors follow national guidelines for managing pulmonary tuberculosis in Pakistan? East Mediterr. Health J. 9(4), 776 788 (2003). 13 Singla N, Sharma PP, Singla R, Jain RC. Survey of knowledge, attitudes and practices for tuberculosis among general practitioners in Delhi, India. Int. J. Tuberc. Lung Dis.. 2(5), 384 389 (1998). 14 Suleiman BA, Houssein AI, Mehta F, Hinderaker SG. Do doctors in north-western Somalia follow the national guidelines for tuberculosis management? East Mediterr. Health J. 9(4), 789 795 (2003). 15 Uplekar MW Shepard DS. Treatment of tuberculosis by private general practitioners in India. Tubercle 72(4), 284 290 (1991). 16 International Standards for Tuberculosis Care (ISTC). Tuberculosis Coalition for Technical Assistance, The Hague, Holland (2006). 17 Hopewell PC, Pai M, Maher D, Uplekar M, Raviglione MC. International standards for tuberculosis care. Lancet Infect. Dis. 6(11), 710 725 (2006). 18 Raviglione M. XDR-TB: entering the postantibiotic era? Int. J. Tuberc. Lung Dis.. 10(11), 1185 1187 (2006). 19 The tuberculosis X factor. Lancet Infect. Dis. 6(11), 679 (2006). 20 Frieden TR, Fujiwara PI, Washko RM, Hamburg MA. Tuberculosis in New York City turning the tide. N. Engl. J. Med. 333(4), 229 233 (1995). 21 Bloch AB, Cauthen GM, Onorato IM et al. Nationwide survey of drug-resistant tuberculosis in the United States. JAMA 271(9), 665 671 (1994). 22 Dolin PJ, Raviglione MC, Kochi A. Global tuberculosis incidence and mortality during 1990 2000. Bull. World Health Organ. 72(2), 213 220 (1994). Affiliations Elizabeth Fair, PhD, MPH University of California, Francis J Curry National Tuberculosis Center, Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, San Francisco, CA 94110, USA Tel.: +1 415 206 3514 Fax: +1 415 695 1551 efair@globalhealth.ucsf.edu Philip C Hopewell, MD University of California, Francis J Curry National Tuberculosis Center, Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, San Francisco, CA 94110, USA Tel.: +1 415 206 3510 Fax: +1 415 695 1551 phopewell@medsfgh.ucsf.edu Madhukar Pai, MD, PhD Assistant Professor, McGill University, Department of Epidemiology, Biostatistics and Occupational Health, 1020 Pine Avenue West, Montreal, Quebec, H3A 1A2, Canada Tel.: +1 514 398 5422 Fax: +1 514 398 4503 madhukar.pai@mcgill.ca www.future-drugs.com 65