The World Health Organization (WHO) has issued updated and consolidated guidelines for programmatic management of Latent Tuberculosis Infection (LTBI). Simultaneously, it is releasing a mobile app to support programmatic management of LTBI.

Background Information:

Latent tuberculosis infection (LTBI) is defined as a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens with no evidence of clinically manifest active TB.

There is no gold standard test for LTBI.

The WHO guidelines on LTBI consider the probability of progression to active TB disease in a specific risk group, the epidemiology and burden of TB, the availability of resources and the likelihood of a broad public health impact.

These guidelines supersede previous WHO policy documents on the management of LTBI in people living with HIV and household contacts of people with TB and other at-risk groups.

Key Messages:

Up to one third of the world’s population is estimated to be infected with Mycobacterium tuberculosis, and on average, 5–10% of those who are infected will develop active TB disease over their lifetime. The risk for active TB disease after infection depends on several factors, the most important being immunological status.

The programmatic management of latent tuberculosis infection (LTBI) in populations most at risk of developing TB remains a critical activity to disrupt Mycobacterium tuberculosis transmission, as identified in the End TB Strategy.

Specific Recommendations:

A. Identification of at-risk populations for LTBI testing and treatment

Adults, adolescents, children and infants living with HIV

Adults, adolescents, children and infants living with HIV, with unknown or a positive tuberculin skin test (TST) and are unlikely to have active TB should receive preventive treatment of TB as part of a comprehensive package of HIV care. Treatment should be given to these individuals irrespective of the degree of immunosuppression and also to those on antiretroviral treatment (ART), those who have previously been treated for TB and pregnant women.

Infants aged < 12 months living with HIV who are in contact with a case of TB and are investigated for TB should receive 6 months of isoniazid preventive treatment (IPT) if the investigation shows no TB disease.

Children aged ≥ 12 months living with HIV who are considered unlikely to have TB disease on the basis of screening for symptoms and who have no contact with a case of TB should be offered 6 months of IPT as part of a comprehensive package of HIV prevention and care if they live in a setting with a high prevalence of TB.

All children living with HIV who have successfully completed treatment for TB disease may receive isoniazid for an additional 6 months.

HIV-negative household contacts

HIV-negative 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.

In countries with a low TB incidence, adults, adolescents and children who are household contacts of people with bacteriologically confirmed pulmonary TB should be systematically tested and treated for LTBI.

In countries with a high TB incidence, 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.

Other HIV-negative at-risk groups

Patients

• initiating anti-TNF treatment,
• receiving dialysis,
• preparing for an organ or haematological transplant and
• patients with silicosis

should be systematically tested and treated for LTBI.

In countries with a low TB incidence, systematic testing for and treatment of LTBI may be considered for prisoners, health workers, immigrants from countries with a high TB burden, homeless people and people who use illicit drugs.

Systematic testing for LTBI is not recommended for

• people with diabetes,
• people with harmful alcohol use,
• tobacco smokers and
• underweight people

unless they are already included in the above recommendations.

B. Algorithms to rule out active TB disease

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.

Chest radiography may be offered to people living with HIV and on ART and preventive treatment given to those with no abnormal radiographic findings.

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 that cause such symptoms. 

Infants and children living with HIV who have poor weight gain, fever or current cough or who have a history of contact with a case of TB should be evaluated for TB and other diseases that cause such symptoms. If the evaluation shows no TB, these children should be offered preventive treatment, regardless of their age.

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 at-risk groups before preventive treatment. 

C. Testing for LTBI

Either a tuberculin skin test (TST) or interferon-gamma release assay (IGRA) can be used to test for LTBI.

People living with HIV who have a positive test for LTBI benefit more from preventive treatment than those who have a negative LTBI test; LTBI testing can be used, where feasible, to identify such individuals.

LTBI testing by TST or IGRA is not a requirement for initiating preventive treatment in people living with HIV or child household contacts aged < 5 years. 

D. Treatment options for LTBI

Isoniazid monotherapy for 6 months is recommended for treatment of LTBI in both adults and children in countries with high and low TB incidence.

Rifampicin plus isoniazid daily for 3 months should be offered as an alternative to 6 months of isoniazid monotherapy as preventive treatment for children and adolescents aged < 15 years in countries with a high TB incidence. 

Rifapentine and isoniazid weekly for 3 months may be offered as an alternative to 6 months of isoniazid monotherapy as preventive treatment for both adults and children in countries with a high TB incidence.

The following options are recommended for treatment of LTBI in countries with a low TB incidence as alternatives to 6 months of isoniazid monotherapy:

• 9 months of isoniazid, or
• a 3-month regimen of weekly rifapentine plus isoniazid, or
• 3–4 months of isoniazid plus rifampicin, or
• 3–4 months of rifampicin alone.

In settings with high TB incidence and transmission, adults and adolescents living with HIV who have an unknown or a positive TST and are unlikely to have active TB disease should receive at least 36 months of IPT, regardless of whether they are receiving ART. IPT should also be given irrespective of the degree of immunosuppression, history of previous TB treatment and pregnancy.

E. Preventive treatment for contacts of patients with multidrug-resistant-TB

In selected high-risk household contacts of patients with multidrug-resistant tuberculosis, preventive treatment may be considered based on individualised risk assessment and a sound clinical justification.

Useful Links:

Link to WHO news release accompanying the release of the updated and consolidated guidelines:

http://www.who.int/tb/features_archive/WHO_recommendations_TB_prevention/en/

Link to the Updated and Consolidated Guidelines:

http://www.who.int/tb/publications/2018/latent-tuberculosis-infection/en/

Link to WHO’s Frequently Asked Questions on LTBI:

http://www.who.int/tb/publications/2018/ltbi_faqs.pdf?ua=1

Link to WHO page containing details of new LTBI app:

http://www.who.int/tb/areas-of-work/preventive-care/ltbi/ltbi_app/en/