Latent tuberculosis infection (LTBI) is defined as a state of persistent immune response to stimulation by M. tuberculosis antigens with no evidence of clinically manifest active TB. It is estimated that about a quarter of the world’s population is infected with TB. TB preventive treatment (TPT) is one of the key interventions recommended by WHO to achieve the End TB Strategy targets, as upheld by the UN High Level Meeting on TB in September 2018. TPT fits within a larger framework of preventive actions envisaged by Pillars 1 and 2 of the End TB Strategy, ranging from screening for active TB, infection control, prevention and care of HIV and other co-morbidities and health risks, access to universal health care, social protection and poverty alleviation.
WHO guidelines on LTBI consider the probability of progression to active TB disease in specific risk groups, the epidemiology and burden of TB, and the likelihood of a broad public health impact. Recommendations are meant primarily for staff in ministries of health and for other policy-makers working on TB, HIV, infectious diseases and maternal and child health. The 2020 WHO consolidated guidelines on tuberculosis: tuberculosis preventive treatment builds upon the previous edition of the document. Its main objectives were to reflect new evidence on shorter rifamycin-containing preventive regimens from trials reported after the 2018 edition of the guidelines were released and to improve the clarity and global applicability of its recommendations. These guidelines supersede previous WHO policy documents on the management of LTBI in people living with HIV (PLHIV), household contacts of people with TB and other risk groups.
The WHO consolidated guidelines on tuberculosis: tuberculosis preventive treatment were prepared in accordance with the requirements of the Guideline Review Committee. The Guideline Development Group (GDG) considered the quality of the latest available evidence on effectiveness and harms, as well as certainty of the evidence, values and preferences, and issues of equity, resource use, acceptability and feasibility of implementation when updating or formulating new recommendations and determining their strength. The GDG considered the implications of the best available evidence for each population subgroup at risk, their likelihood of progression from infection to active TB and the incidence of active TB as compared with that in the general population. The GDG used the guiding principle that individual benefit outweighs risk as the mainstay of recommendations on LTBI testing and TPT. LTBI testing is desirable whenever feasible to identify persons at highest risk for developing active TB. Any additional resources needed to implement the guidance should not be viewed as a barrier but should stimulate programmatic action to mobilise appropriate levels of funding.
The 18 recommendations in the WHO consolidated guidelines on tuberculosis: tuberculosis preventive treatment cover critical steps in the programmatic management of TPT (PMTPT) and follow the cascade of preventive care: identification of populations at risk (PLHIV as part of the HIV care package, household contacts and others), ruling out active TB disease, testing for LTBI, providing treatment, and monitoring adverse events, adherence and completion of treatment (Table 1). Most of the recommendations dating from the 2018 update remain largely unchanged. The changes introduced in 2020 relate primarily to the inclusion of a 1-month daily rifapentine and isoniazid regimen and a 4-month daily rifampicin regimen as alternative TB preventive treatment options in all settings subject to specific conditions. Advice on isoniazid preventive treatment in pregnancy and on the concomitant use of rifapentine and dolutegravir now reflects findings from latest available studies. Certain recommendations – previously restricted by national TB incidence thresholds out of concerns of intensity of TB transmission, programmatic capacity to rule out active TB, and resource implications to implement a new intervention at scale – are now applicable to any country subject to setting-specific conditions. The operational limitations that need to be urgently overcome by countries to achieve global targets are highlighted. The publication of the new guidelines will be followed shortly after with the release of an operational guide containing practical details on the programmatic implementation of the updated guidance. These two publications are being issued as modular components of a new consolidated set of guidelines and operational guides that will group together other WHO normative documents on TB.
Main changes to the guidance in the current update
(see also Supplementary Table)
- the text of five recommendations was edited to reflect their applicability regardless of the TB burden in the country or setting, and additional commentary added to highlight the implications for their use in settings that differ in TB burden and resources
- recommendations and accompanying considerations for TB preventive treatment in contacts and clinical and occupational risk groups have been slightly reworded to remove any undue stress on their application to HIV negative individuals only
- three previous recommendations on the systematic LTBI testing and TB preventive treatment in low burden settings and in PLHIV and household contacts under 5 years of age before the start of treatment are now presented amongst the implementation considerations
- one recommendation has been updated to include both 1HP and 4R as options for TB preventive treatment in all settings
- three previous recommendations on the use of 6H, 3HR in people under 15 years of age and 3HP in high TB prevalence settings no longer feature by themselves as these regimen options are now covered by one recommendation that lists all acceptable TB preventive treatment options in any setting
- the variable durations of 3–4 months of daily rifampicin and 3–4 months of daily rifampicin plus isoniazid in the previous recommendation have been simplified to 4 and 3 months respectively, being the length of time for which these treatments are usually given
- a single algorithm replaces the four in the 2018 guidance, harmonizing the key decision points for LTBI testing and TB preventive treatment of individuals at risk
- the content of the guidelines has been updated, citing recent references and latest available evidence, such as on use of rifapentine with dolutegravir and isoniazid preventive treatment in pregnant women with HIV
- the research gaps have been updated to reflect the latest evidence reviewed
² The recommendations in the current update are compared with those in the 2018 guidelines in the supplementary table.