2010年WHO肺结核治疗指南

Major progress in global TB control followed the widespread implementation of the DOTS strategy. The Stop TB Strategy, launched in 2006, builds upon and enhances the achievements of DOTS : new objectives include universal access to patient-centred treatment, and protection of populations from TB/HIV coinfection and multidrug-resistant TB (MDR-TB). The Stop TB Strategy and the Global Plan to implement the new strategy made it necessary to revise the existing guidelines and develop this fourth edition.

Historically, the greatest emphasis of TB control activities has been on the most infectious patients – those who have sputum smear-positive pulmonary tuberculosis. This changed with the Stop TB Strategy’s emphasis on universal access for all persons with TB to high-quality, patient-centred treatment. However, highly infectious, smear-positive patients remain the primary focus for other aspects of TB control, including contact tracing and infection control. The Patients’ Charter for TB Care specifies that all TB patients have “the right to free and equitable access to TB care, from diagnosis through treatment completion”.

This fourth edition of the guidelines has therefore abandoned Categories I–IV, which were used to prioritize patients for treatment.1 According to this prior categorization, smear-negative TB patients were assigned third priority and MDR-TB patients fourth priority. For treatment decisions it no longer makes sense to assign third priority to smear-negative patients given their high mortality if they are living with HIV. Equally, MDR-TB patients should not be assigned fourth priority, given their high mortality and the urgent need to prevent the spread of these deadliest TB strains.

To replace Categories I–IV, this fourth edition groups patients (and standard regimens recommended for each group) according to the likelihood of their having drug resistance. Drug resistance is a critical determinant of treatment success, and prior TB treatment confers an increased risk. This edition uses the same patient registration groups as those used for recording and reporting, which differentiate new patients from those who have had prior treatment. Registration groups for previously treated patients are based on the outcome of their prior treatment course: failure, relapse, and default.

The fourth edition integrates detection and treatment of both HIV infection and MDR-TB, and thus should contribute towards achievement of the Stop TB Strategy’s universal access to high-quality MDR-TB and HIV care.

With regard to HIV detection, this edition incorporates recent WHO recommendations for provider-initiated HIV testing of all persons with diagnosed or suspected TB, in all types of HIV epidemics (low-level, concentrated or generalized). For treatment of TB in persons living with HIV, new  recommendations on the duration of therapy and the role of intermittent regimens have emerged from systematic reviews. The new edition also includes recent WHO recommendations for DST at the start of TB therapy in all people living with HIV , as well as recommendations on the timing and type of antiretroviral therapy (ART) regimens.New developments in MDR-TB also contributed to the need for this revision. Building on the principle of universal access to MDR-TB diagnosis and care, The MDR-TB and XDR-TB response plan 2007–2008 calls for the diagnosis and treatment of MDR-TB in all countries by 2015. Even countries with low overall levels of multidrug resistance (MDR) are faced with TB patients who have been previously treated – a group that is five times more likely to have MDR-TB than new patients.

In terms of ensuring universal access to MDR-TB diagnosis, this fourth edition reaffirms existing WHO recommendations that all previously treated patients should have access to culture and DST at the beginning of treatment, in order to identify MDR-TB as early as possible.1 It also incorporates the WHO recommendation that treatment failure be confirmed by culture and DST. In order to detect MDR sooner than the end of the fifth month of treatment, this edition includes the existing WHO recommendation for culture and DST if patients still have smear-positive sputum at the end of the third month of treatment.

Chapters 2–5 of this new edition discuss the critical role of the identification of Mycobacterium tuberculosis and of DST. This is in contrast to the previous edition, which relied almost exclusively on smear microscopy for case definition, assignment of standard regimens, and monitoring of treatment response. Line probe assays can identify MDR-TB within hours and liquid media can do so within weeks (rather than months when solid media are used). These techniques should be introduced in line with comprehensive, country-specific plans for laboratory capacity strengthening.

To move towards universal access to MDR-TB treatment, the fourth edition includes a new recommendation for every country to include an MDR regimen in its standard regimens. This is essential while awaiting DST results for patients with a high likelihood of MDR (such as those whose prior treatment with a 6-month rifampicin regimen has failed), and for patients in whom resistance to isoniazid and rifampicin is confirmed. With the availability of funding from international financial partners, lack of resources for MDR-TB treatment is no longer an acceptable rationale for providing the 8-month retreatment regimen with first-line drugs (formerly called the “Category II regimen”) to patients with a high likelihood of MDR; this regimen is ineffective in treating MDR-TB and may result in amplification of drug resistance.

Use of rapid DST methods will eventually render the 8-month retreatment regimen of first-line drugs obsolete. In the meantime, the regimen is retained in this fourth edition in only two circumstances. In countries with access to routine DST using conventional methods, the 8-month retreatment regimen with first-line drugs is recommended while awaiting DST results from patients who have relapsed or are returning after default (if country-specific data show they have a medium likelihood of MDR-TB, or if such data are unavailable). In countries that do not yet have DST routinely available at the start of treatment for all previously treated patients, the 8-month retreatment regimen with first-line drugs will be used for the duration of treatment on an interim basis until laboratory capacity is available.

In principle, MDR treatment should be introduced only in well-performing DOTS programmes. Before focusing on curing MDR-TB cases, it is critical to “turn off the tap”, i.e. to strengthen poor programmes so that they stop giving rise to MDR-TB. Following this principle, the 2004 revision of the treatment chapter1 listed adequate performance of a country’s overall TB programme as a requirement for the use of MDR regimens in patients with a high likelihood of MDR. This is no longer a prerequisite in the fourth edition. In some countries with limited DOTS coverage, there may be an appropriate setting for an MDR pilot project that, once established, can provide a model and an impetus for the expansion of basic DOTS into more areas. In most countries, however, conditions for initiating an MDR component in most NTPs are not met until the overall NTP has the essential elements of DOTS firmly in place.