The World Health Organization (WHO) has a mandate to develop and disseminate evidence-based policy, norms and standards for tuberculosis (TB) prevention, diagnosis, treatment and care. Hence, the WHO Global TB Programme performs regular reviews of evidence and assessments of country needs for policy updates across the cascade of TB prevention and care. TB guidelines and operational handbooks are now organized under five modules: prevention, screening, diagnosis, treatment and comorbidities, vulnerable populations and people-centred care.
Updated WHO guidelines and handbooks published since the release of the Global tuberculosis report 2020 are summarized here by module, along with a summary of the key recommendations.
In March 2021, WHO released the WHO consolidated guidelines on tuberculosis. Module 2: Screening – systematic screening for tuberculosis disease (1). These guidelines include 17 new and updated recommendations for the screening of TB disease. Populations identified as priorities for TB screening include contacts of TB patients, people living with HIV, people exposed to silica, prisoners and other key populations. The following screening tools are recommended: symptom screening, chest radiography, computer-aided detection (CAD) software, molecular WHO-approved rapid diagnostic tests and testing for C-reactive protein. This is the first time that CAD has been recommended for use in interpreting chest radiography for TB.
The new guidelines are accompanied by the WHO operational handbook on tuberculosis. Module 2: Screening – systematic screening for tuberculosis disease (2). The handbook provides practical advice on how to put the guideline recommendations in place at the scale needed to achieve national and global impact. It is intended to support policy-makers and health professionals to choose the best approach to planning and implementing TB screening and active TB case-finding, depending on the context. The handbook provides a sound basis for the development or updating of national guidelines for TB screening according to the epidemiology of TB in different risk groups and the health care delivery system in the country. This will contribute to finding people with TB who may be missed by passive TB case detection and finding people with TB earlier in the course of their disease, thus reducing transmission, morbidity, mortality and financial hardship.
In July 2021, WHO released the WHO consolidated guidelines on tuberculosis. Module 3: Diagnosis – rapid diagnostics for tuberculosis detection 2021 update (3). Three new classes of nucleic acid amplification test (NAAT) are now endorsed by WHO:
The new recommendations on diagnostics are accompanied by a WHO operational handbook on tuberculosis. Module 3: Diagnosis – rapid diagnostics for tuberculosis detection (4). The handbook aims to facilitate the implementation of WHO guidelines by countries, technical partners and others involved in managing patients with TB and drug-resistant TB. It provides practical information on new and existing tests recommended by WHO and model diagnostic algorithms. The handbook also has step-by-step advice on implementing and scale-up of testing to achieve local and national impact, and an overview of budgetary considerations and information sheets for each of the newly recommended tests.
In June 2021, WHO released a catalogue of Mycobacterium tuberculosis mutations as a reference standard for the interpretation of mutations conferring resistance to all first-line and a variety of second-line TB drugs (5). The report summarises the analysis of over 38,000 isolates with matched data on whole genome sequencing and phenotypic drug susceptibility testing from over 40 countries for 13 anti-TB medicines. It lists over 17,000 mutations, their frequency and association with resistance and includes methods used, mutations identified and summaries of important findings for each drug. This resource will allow laboratories around the world to better interpret the genome sequencing results. The catalogue can also guide the development of new molecular drug susceptibility tests, including next-generation sequencing.
In April 2021, WHO convened a guideline development group (GDG) to review data from a trial conducted in 13 countries that compared 4-month rifapentine-based regimens with a standard 6-month regimen in people with drug-susceptible TB (6). The GDG considered a 4-month regimen composed of rifapentine, isoniazid, pyrazinamide and moxifloxacin that met the non-inferiority criteria set in the trial protocol. The available evidence supports the use of this regimen as a possible alternative to the current standard 6-month regimen. The shorter regimen showed similar performance to the current standard regimen in terms of both efficacy and safety. The 4-month regimen – which is shorter, effective and all-oral – would be preferred by many patients, allowing faster cure and easing the burden on both patients and the health care system. However, implementation and uptake of the new regimen in the short to medium term will be more feasible if the cost of rifapentine is reduced and availability improved. A rapid communication presents key findings and considerations on the use of the 4-month regimen following the GDG assessment (7). The full guidelines will be finalized by the end of 2021 and will be incorporated under Module 4: Treatment of the consolidated guidelines and operational handbook.
In May to June 2021, WHO convened a GDG to review updated evidence on the management of TB in children and adolescents (aged 0–9 and 10–19 years, respectively). A rapid communication that summarizes the main updates to guidance on the management of TB in children and adolescents was released by WHO in August 2021 (8). The communication includes new information about treatment decision algorithms, the use of Xpert MTB/RIF Ultra to diagnose pulmonary TB using gastric aspirate and stool specimens, a 4-month regimen to treat non-severe, drug-susceptible pulmonary TB, the use of bedaquiline and delamanid to treat drug-resistant TB, a shortened intensified regimen for TB meningitis, and optimal models of care for the delivery of child and adolescent TB services. The aim is to inform staff from ministries of health, technical partners and other stakeholders about the key findings, considerations and changes related to the diagnosis, treatment and care of TB for children and adolescents, to allow for planning at the country level. Based on the outcomes of the GDG meeting, detailed recommendations will be published as part of the WHO consolidated guidelines on tuberculosis. Module 5: Co-morbidities, vulnerable populations and people-centred care, alongside an operational handbook; both documents will be published by the end of 2021.
Refugees and other displaced populations in humanitarian emergencies face significant threats to health and survival, including poverty, crowded living conditions, undernutrition and poor access to health care. These conditions predispose people to an increased risk of TB infection and development of disease. WHO, in collaboration with the United Nations (UN) High Commissioner for Refugees (UNHCR) and the United States Centers for Disease Control and Prevention (US CDC), will shortly release a field guide to address the challenge of TB in refugees. This guide will include new strategic approaches, guidance and innovations on TB prevention and care interventions in humanitarian crisis situations, to prevent and alleviate the suffering and deaths caused by TB among refugees and displaced populations. Its relevance is underlined by the continued large-scale population movements worldwide induced by conflict, poverty, natural disasters and a changing climate.
To exchange views on emerging areas where there is a need for global TB policy guidance, in March 2021, WHO convened a consultation on the translation of TB research into global policy guidelines, attended by scientists, public health experts, partners, civil society and countries (9).
In June 2021, WHO launched a TB Knowledge Sharing Platform to bring all WHO TB guidelines, operational handbooks and training material together in one place (10). In addition to the desktop site, the content is also available on applications for smartphones and tablet computers.[1] It is envisaged that the Knowledge Sharing Platform will become the main portal for dissemination of WHO’s TB guideline-related content, ensuring that the latest guidance and implementation aids are available in one place.
Throughout the year, the Global TB Programme continued to update its repository of WHO recommendations relevant to TB care on its WHO endTB Guidelines website (11). The database provides health care workers, decision-makers, researchers and other users with an efficient way to search and locate the latest TB guidance based on their questions of interest, with built-in search, filter and cross-tabulate functions (12). The site also gives access to evidence to decision (EtD) frameworks, study citations, and summaries of findings, providing a transparent link to the data and GDG judgements underpinning each recommendation.
[1] Find the WHO TB Guide on Google Play or the Apple App Store.
References