The World Health Organization (WHO) has recently released new recommendations for Tuberculosis preventive treatment (TPT).
Background Information:
Definitions:
Adolescent: A person aged 10–19 years
Adult: A person over 19 years of age
Bacteriologically confirmed TB: TB diagnosed in a biological specimen by smear microscopy, culture or a WHO-approved molecular test such as Xpert® MTB/RIF
Child: A person under 10 years of age
Contact: Any person who was exposed to a person with tuberculosis
Contact investigation: A systematic process for identifying previously undiagnosed people with TB among the contacts of an index case. Contact investigation consists of identification and prioritization and clinical evaluation. It may also include testing for LTBI to identify candidates for TB preventive treatment.
High TB transmission setting: A setting with a high frequency of individuals with undetected or undiagnosed active TB, or where infectious TB patients are present and there is a high risk of TB transmission.
TB patients are most infectious when they are untreated or inadequately treated. Spread is increased by aerosol-generating procedures and by the presence of highly susceptible individuals.
Household contact: A person who shared the same enclosed living space as the index case for one or more nights or for frequent or extended daytime periods during the 3 months before the start of current treatment.
Index case (index patient) of TB: The initially identified person of any age with new or recurrent TB in a specific household or other comparable setting in which others may have been exposed. An index case is the person on which a contact investigation is centred but is not necessarily the source case.
Infant: A child under 1 year (12 months) of age
Latent tuberculosis infection (LTBI): A state of persistent immune response to stimulation by M. tuberculosis antigens with no evidence of clinically manifest active TB. This is also at times referred to as TB infection. There is no gold standard test for direct identification of M. tuberculosis infection in humans. Most infected people have no signs or symptoms of TB but are at risk for active TB disease.
Programmatic management of tuberculosis preventive treatment (PMTPT): All coordinated activities by public and private health caregivers and the community aimed at scaling up TB preventive treatment to people who need it.
TB preventive treatment (TPT): Treatment offered to individuals who are considered at risk of TB disease in order to reduce that risk. Also referred to as treatment of TB infection, LTBI treatment or TB preventive therapy.
Tuberculosis (TB): The disease state due to M. tuberculosis. Here, it is commonly referred to as “active” TB or TB “disease” in order to distinguish it from TB infection.
Underweight: in adults usually refers to a body mass index <18.5 and in children < 10 years to a weightfor-age < –2 z-scores
About one fourth of the world’s population is estimated to be infected with M. tuberculosis. The vast majority have no signs or symptoms of TB disease and are not infectious, although they are at risk of developing active TB disease and becoming infectious. Several studies have shown that in recent decades, on average, 5–10% of those infected will develop active TB disease over the course of their lives, usually within the first 5 years after initial infection- 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.
The risk for active TB disease after infection depends on several factors, the most important being immunological status. At the first United Nations high-level meeting on TB in 2018, Member States committed to provide TB preventive treatment to at least 30 million people in 2018–2022:
- 6 million people living with HIV (PLHIV),
- 4 million children < 5 years who are household contacts of people with TB, and
- 20 million other household contacts.
Prevention of active TB disease by TB preventive treatment is a critical component of the WHO End TB Strategy and efforts to eliminate TB. The efficacy of currently available TB preventive treatment ranges from 60% to 90%.
Key Messages:
Recommendations:
A. Identifying populations for LTBI testing and TB preventive treatment
People living with HIV
- Adults and adolescents living with HIV who are unlikely to have active TB should receive TB preventive treatment as part of a comprehensive package of HIV care. Treatment should be given to those on antiretroviral treatment, to pregnant women and to those who have previously been treated for TB, irrespective of the degree of immunosuppression and even if LTBI testing is unavailable. (Strong recommendation, high certainty in the estimates of effect)
Infants and children living with HIV
- Infants aged < 12 months living with HIV who are in contact with a person with TB and who are unlikely to have active TB on an appropriate clinical evaluation or according to national guidelines should receive TB preventive treatment. (Strong recommendation, moderate certainty in the estimates of effect)
- Children aged ≥ 12 months living with HIV who are considered unlikely to have active TB on an appropriate clinical evaluation or according to national guidelines should be offered TB preventive treatment as part of a comprehensive package of HIV prevention and care if they live in a setting with high TB transmission, regardless of contact with TB. (Strong recommendation, low certainty in the estimates of effect)
- All children living with HIV who have successfully completed treatment for TB disease may receive TB preventive treatment. (Conditional recommendation, low certainty in the estimates of effect)
Household contacts (regardless of HIV status)
- Children aged < 5 years who are household contacts of people with bacteriologically
confirmed pulmonary TB and who are found not to have active TB on an appropriate clinical evaluation or according to national guidelines should be given TB preventive treatment even if LTBI testing is unavailable. (Strong recommendation, high certainty in the estimates of effect) - Children aged ≥ 5 years, adolescents and adults who are household contacts of people with bacteriologically confirmed pulmonary TB who are found not to have active TB by an appropriate clinical evaluation or according to national guidelines may be given TB preventive treatment. (Conditional recommendation, low certainty in the estimates of effect)
Contacts of multi-drug resistant tuberculosis patients
- In selected high-risk household contacts of patients with multidrug-resistant tuberculosis, preventive treatment may be considered based on individualized risk assessment and a sound clinical justification. (Conditional recommendation, very low certainty in the estimates of effect)
Other people at risk
- People who are initiating anti-TNF treatment, or receiving dialysis, or preparing for an organ or haematological transplant, or who have silicosis should be systematically tested and treated for LTBI. (Strong recommendation, low to very low certainty in the estimates of effect)
- Systematic LTBI testing and treatment may be considered for prisoners, health workers, immigrants from countries with a high TB burden, homeless people and people who use drugs. (Conditional recommendation, low to very low certainty in the estimates of effect).
- Systematic LTBI testing and treatment is not recommended for people with diabetes, people who engage in the harmful use of alcohol, tobacco smokers and underweight people unless they also belong to other risk groups included in the above recommendations. (Conditional recommendation, very low certainty in the estimates of effect)
B. Algorithms to rule out active TB disease
People living with HIV
- Adults and adolescents living with HIV should be screened for TB according to a clinical algorithm. Those who do not report any of the symptoms of current cough, fever, weight loss or night sweats are unlikely to have active TB and should be offered preventive treatment, regardless of their ART status. (Strong recommendation, moderate certainty in the estimates of effect)
- Adults and adolescents living with HIV who are screened for TB according to a clinical algorithm and who report any of the symptoms of current cough, fever, weight loss or night sweats may have active TB and should be evaluated for TB and other diseases and offered preventive treatment if active TB is excluded. (Strong recommendation, moderate certainty in the estimates of effect)
- Chest radiography may be offered to people living with HIV on ART and preventive treatment be given to those with no abnormal radiographic findings. (Conditional recommendation, low certainty in the estimates of effect)
- Infants and children living with HIV who have poor weight gain, fever or current cough or who have a history of contact with a person with TB should be evaluated for TB and other diseases that cause such symptoms. If TB disease is excluded after an appropriate clinical evaluation or according to national guidelines, these children should be offered TB preventive treatment, regardless of their age. (Strong recommendation, low certainty in the estimates of effect)
Household contacts aged ≥5 years and other risk groups
- The absence of any symptoms of TB and the absence of abnormal chest radiographic findings may be used to rule out active TB disease among HIV-negative household contacts aged ≥ 5 years and other risk groups before preventive treatment. (Conditional recommendation, very low certainty in the estimates of effect)
C. Testing for LTBI
- Either a tuberculin skin test (TST) or interferon-gamma release assay (IGRA) can be used to test for LTBI. (Strong recommendation, very low certainty in the estimates of effect)
D. TB preventive treatment options
- The following options are recommended for the treatment of LTBI regardless of HIV status:
- 6 or 9 months of daily isoniazid, or
- a 3-month regimen of weekly rifapentine plus isoniazid, or
- a 3 month regimen of daily isoniazid plus rifampicin. (Strong recommendation, moderate to high certainty in the estimates of effect).
Alternatives
- A 1-month regimen of daily rifapentine plus isoniazid or
- 4 months of daily rifampicin alone. (Conditional recommendation, low to moderate certainty in the estimates of effect).
- In settings with high TB transmission, adults and adolescents living with HIV who have an unknown or a positive LTBI test and are unlikely to have active TB disease should receive at least 36 months of daily isoniazid preventive treatment (IPT).
Daily IPT for 36 months should be given whether or not the person is on ART, and irrespective of
- the degree of immunosuppression,
- history of previous TB treatment and pregnancy
in settings considered to have a high TB transmission as defined by national authorities. (Conditional recommendation, low certainty in the estimates of effect).
Useful Links:
Link to the related WHO news release:
Link to the WHO Consolidated guidelines:
Link to the WHO Operational Handbook:
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