WHO Announces New Management of Latent TB Infection

For the first time, the World Health Organization (WHO) has issued guidelines on testing, treating and managing latent TB infection (LTBI) in individuals with high risk of developing the disease. These guidelines were launched today at the Global TB Symposium just before the start of the 45th Union World Conference on Lung Health in Barcelona.

“Prevention of TB and the management of latent TB is one of the key elements of the new END-TB strategy of WHO to be pursued primarily in all low-incidence countries,” said Dr Mario Raviglione, Director of the Global TB Programme of the WHO.

The new guidelines on the management of LTBI provide public health approach guidance on evidence-based practices for testing, treating and managing LTBI in infected individuals with the highest likelihood of progression to active disease.

“These guidelines respond to the request of several Member States for a clear WHO guidance and provide the framework for the development of national guidelines for the management of latent TB” said Dr Haileyesus Getahun, Coordinator for TB/HIV and Community Engagement, WHO Global TB Programme, while releasing the new guidelines.

Dr Getahun further said to Citizen News Service (CNS) that, “The guidelines primarily target higher and middle income countries with an estimated TB incidence rate of less than 100 per 100 000 population because they are most likely to benefit from the guidelines due to their current TB epidemiology and resource availability.”

These criteria are currently met by 113 countries. Resource-limited and other middle-income countries that do not belong to the above category are advised to implement the existing WHO guidelines on people living with HIV (PLHIV) and child contacts below 5 years of age.

What Is LTBI?

It is defined as a state of persistent immune response to stimulation by Mycobacterium TB antigens without evidence of clinically manifested active TB- which means that people have been infected by TB bacteria but do not show symptoms of TB and cannot transmit the disease. Years ago Dr William Osler had rightly said that LTBIs are the seedbeds of TB in the community.

It is estimated that globally 30% of the world’s population has latent TB-ranging from 14% in the European region to 46% in Sout East Asia. These people have a 5%-10% lifetime risk of falling ill with TB. However the risk is higher in persons with compromised immune systems. Reactivation of latent TB significantly contributes to the TB burden particularly in low incidence countries.This can be averted by preventive treatment. Currently available preventive treatment regimens can prevent TB with an efficacy ranging between 60% to 90%.

Key Recommendations of The Guidelines

Selecting those who should be tested:

The guidelines recommend that:

Systematic testing and treatment of LTBI should be considered for:

  • PLHIV, adult and child contacts of pulmonary TB patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematologic transplantation, and patients with silicosis
  • prisoners, health-care workers, immigrants from high TB burden countries, homeless persons and illicit drug users.
  • Systematic testing for LTBI is not recommended in people with diabetes, people with harmful alcohol use, tobacco smokers, and underweight people provided they are not already included in the above recommendations.

  • Individuals should be asked about symptoms of TB before being tested for LTBI.
  • Standards for Testing and Treatment

    LTBI diagnosis and treatment recommendations in the guidelines are based upon a public health approach with individual benefit, keeping in mind that they complement active TB case finding activities and that individual benefits should outweigh the risk.

    The guidelines recommend that either tuberculin skin test (TST) or interferon gamma release assays (IGRA) can be used to test for latent TB.

    Consistent with existing WHO recommendations, the guidelines reiterated that IGRAs should not replace TST in low and middle income countries.

    The following treatment options are recommended for the treatment of LTBI in the guidelines:

    1. isoniazid daily for 6 months (6H)
    2. isoniazid daily for 9 months (9H)
    3. the combination of rifapentine and isoniazid once a week for 12 weeks (3HP)
    4. the combination of rifampicin and isoniazid daily for 3-4 months (3-4HR)
    5. rifampicin alone daily for 3-4 months (3-4R)

    “Currently, these are the only diagnostic tests available though they are both weak in predicting future development of TB among infected. Development of better diagnostic tools should be priority for research” said Dr Alberto Matteelli, Medical officer from the TB/HIV and community engagement unit.

    Critical Issues for Implementating Guidelines

    In Addition, The Guidelines Development Panel Noted The Following Critical Issues for Consideration in The Implementation of These Guidelines:

    Strict clinical observation and close monitoring for the development of active TB disease among contacts of multidrug-resistant TB (MDR-TB) cases, preferably for at least two years over the provision of preventive treatment;

    Regular clinical monitoring of individuals receiving treatment for latent TB through a monthly visit to the health-care provider;

    Establishment of national TB drug resistance surveillance systems while implementing national latent TB management services;

    Introduction of flexible interventions and incentives by national TB programmes that are responsive to the specific needs of population groups at risk, as well as tailored to the local context and their needs to ensure acceptable initiation of, adherence to and completion of LTBI treatment.

    Documentation of treated individuals through a functional, routine monitoring and evaluation system that is aligned with national patient monitoring and surveillance systems.

    Creation of conducive policy and programmatic environment, including the promotion of universal health coverage, development of national and local policies, standard operating procedures, as well allocation of dedicated resources.

    PUBLIC HEALTH APPROACH AND RESOURCE ALLOCATION ARE ESSENTIAL

    The management of LTBI requires a comprehensive package of interventions and public health measures. Critical public health considerations for routine monitoring and evaluation include: initiation and completion of treatment, active surveillance of adverse events and the development of active TB during and after the completion of treatment for latent TB. Additionally, programme monitoring is needed to evaluate quality, effectiveness and impact.

    Creation of a conducive policy and programmatic environment, including the promotion of universal health coverage, development of national and local policies, standard operating procedures, as well allocation of dedicated resources is essential to facilitate the implementation of the recommendations.

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