About one fourth of the world’s population is estimated to be infected with M. tuberculosis (1,2). The risk of TB disease after infection depends on several factors, the most important being weakened immunological status (3). The vast majority of infected individuals show no signs or symptoms of TB and are not infectious, although they have an increased risk of progressing to TB disease and becoming infectious. On average, about 5–10% of those infected will develop TB disease over the course of their lives, most of them within the first five years after initial infection (4). Studies have found that about 75% of people who develop active disease after coming into contact with someone with TB do so within one year of TB diagnosis of the index patient, and 97% develop TB within two years (5). Molecular typing studies in low-burden settings have also found that, among those who develop disease within 15 years of exposure, probabilities of developing disease within one, two and five years were 45%, 62% and 83%, respectively (6). Therefore, people living with human immunodeficiency virus (PLHIV), individuals in contact with TB patients and those with immunodeficiency conditions are at high risk of TB and hence are priority groups to receive TB preventive treatment (TPT). Unfortunately, biomarkers and tests for TB infection available currently cannot differentiate between recent and remote infection. The eligibility for TPT relies on ruling out TB disease clinically and radiologically among individuals and groups who are known to be at high risk of acquiring TB, using the tests just as an aid in decision-making when available.
The WHO End TB Strategy prioritized TPT among persons at high risk, as a key component under Pillar 1. The programmatic management of TPT (PMTPT) fits within a larger framework of preventive actions envisaged under Pillars 1 and 2 of the End TB Strategy, and includes screening for TB disease, infection control, prevention and care of HIV and other comorbidities, access to universal health care, social protection and poverty alleviation (7). The End TB strategy provides indicators to monitor progress and set a global target to achieve 90% coverage of TPT among PLHIV and household contacts of TB patients by 2025 (8). PMTPT is also considered a key intervention for low TB burden countries that are pursuing TB elimination (9). While TPT services are gradually expanding globally, access among persons at risk remains low. In 2018, about 1.8 million PLHIV, 350 000 children under five years of age and nearly 80 000 people aged five years or above were reported by countries to have received TPT (10). Coverage of contacts thus remains very low with an absolute priority for the United Nations High-Level Meeting (UNHLM) targets to be met.
In September 2018, at the first ever UNHLM on Tuberculosis, Member States endorsed a political declaration committing to diagnose and treat 40 million people with TB by the end of 2022 and provide 30 million individuals with TPT to protect them from development of TB disease during this period (11). The TPT target in the declaration includes 6 million PLHIV, 4 million children under five years of age who are contacts of TB patients, and 20 million other household contacts of TB patients. Achievement of these targets entails a massive expansion of TPT services through health system strengthening and a mobilization of commensurate human and financial resources. In this context ministries of health need to take urgent actions to redesign PMTPT and mobilize resources to support rapid scale-up of TPT aligned with the latest (2020) guidelines from the World Health Organization (WHO) (12). Table 1.1 lists the latest WHO recommendations on TPT, that are discussed further in this handbook.
In support of these guidelines, this operational handbook lays down key implementation considerations and steps in the programmatic scale-up of TPT and provides implementation tools and job-aids for adaptation to the local context, and monitoring and evaluation indicators for PMTPT. It highlights key elements to consider in patient care, national strategic planning and resource mobilization. Although the handbook focuses on settings with a high TB and HIV burden, implementation considerations may apply also to low TB burden settings. This handbook is intended to guide policy-makers within the ministries of health and other institutions, and stakeholders that have an impact on health, including HIV and TB programme managers at national, subnational and district levels; health care workers and staff of development and technical agencies, nongovernmental organizations (NGOs) as well as civil society and community-based organizations involved in supporting TPT services.
Cascade of care approach
PMTPT has long been a low priority intervention for national programmes due to other competing priorities. However, with Member States committed to take urgent steps towards ending the TB epidemic (11), major investments towards health systems strengthening should be made and a comprehensive ‘cascade of care’ approach adopted to scale up PMTPT (13). Advocacy efforts at different levels are critically important in the process and some key messages have been included in this handbook (see Annex 1; which includes an informative flyer developed by the WHO South-East Asia Region and the Global Coalition of TB Activists as an example that can be adapted elsewhere as well as a joint Call to Action to scale up TPT globally issued by partners in May 2020). It is important to ensure that all individuals most at risk of developing TB are systematically identified and provided access to a full course of TPT to improve individual health and reduce ongoing TB transmission. This is challenging as losses in the cascade of care prior to starting TPT are significant, even more than that from patient non-adherence to therapy after starting. A systematic review and meta-analysis in 2015 showed that the steps in the cascade of care associated with greatest losses were: initial testing of those intended for TB screening, completing medical evaluation if the test was positive, provider recommendation of treatment, and completing therapy when started. Overall, among those estimated to be eligible for TPT, less than 20% completed the entire cascade of care (14). It should be noted that these data were from research studies in developed countries, and losses under programmatic conditions in resource-constrained settings are expected to be even higher. Concerted efforts by national programmes and other stakeholders are necessary to enhance the reach of services for recommended target populations (14).
Programmatic implementation and scale-up of TPT services requires strengthening of each element in the cascade of care starting from identification of the target population to provision of preventive treatment (Fig. 1.1). Annexes 2, 3 and 4 present suggestions for in-country structures to coordinate activities, costing considerations in budgeting as well as technical advice for PMTPT. TPT services should be integrated with efforts for TB case finding among target populations. Presumptive TB patients among target populations should receive diagnostic testing for TB with rapid molecular tests, and TB treatment if found positive. When TB disease is ruled out the individual should be evaluated for TB infection and receive TPT (see also algorithm in Fig. 4.1). Better retention and referral of individuals evaluated for TB, identification of those eligible for TPT and development of more person-friendly and accessible services will ensure that a substantial proportion of people with TB infection are initiated on TPT and complete the treatment, thereby reducing the reservoir of TB infection from which TB disease develops (15). This handbook is organized around the cascade of care and highlights elements that require programmatic prioritization and investment at each stage.
At each step of the cascade of care, national programmes and stakeholders should: prioritize the adoption of relevant national policy to facilitate implementation; earmark investment to strengthen health systems and enhance human resources; build capacity of providers; promote rapid scale-up of the latest diagnostic tools and shorter TPT regimens; generate demand for services; strengthen supervision and monitoring; and establish mechanims for ongoing review and programme adjustments with the goal of national coverage of TPT services among all at-risk populations (Fig. 1.2).
This document outlines key decision points on policy considerations, health system requirements and areas for additional investment at each step in the cascade of care. A set of standard indicators for monitoring and evaluation of TPT services is also included along with suggested data variables to be captured in the national health management information system (HMIS) preferably using digital tools to minimize the reporting burden on health care workers. The policy considerations suggested are aligned with the latest WHO guidelines (Table 1.1). The overall aim is to support country efforts to achieve their individual contributions to the global targets for TPT.
Key point: Achievement of the UNHLM targets to provide TPT to at least 30 million individuals between 2018 and 2022, requires collective efforts and investments from governments, donors and other stakeholders to: strengthen health system across the cascade of care for TB, enhance provider and community awareness on importance of TPT, and ensure rapid access to latest tools for detection of TB infection and shorter TPT regimens.
¹ The conditions under which these recommendations apply and more details on their implementation are discussed in the following chapters.