WHO released new guidance that aims to expand testing and treatment options for latent tuberculosis, as well as the types of patients that are prioritized for care.
The guidance includes 24 existing, updated and new recommendations. They were issued in response to requests from several WHO member states that claimed the agency’s previous recommendations for latent TB were “fragmented” and difficult to implement.
“The scale-up of TB preventive treatment has been slow. Only 12 of the 30 countries with a high burden of HIV-associated TB reported provision of TB preventive treatment in 2016,” Haileyesus Getahun, MD, PhD, MPH, coordinator for WHO’s Global TB Program, said in a news release. “We hope the new guidelines will disrupt the status quo in many countries and leapfrog global implementation of TB prevention efforts.”
Reprioritizing high-risk patients
WHO’s previous recommendations prioritized testing and treatment for people living with HIV and children aged younger than 5 years who are contacts of patients with TB. The agency now considers all patients exposed to TB or multidrug-resistant (MDR)-TB — regardless of age or HIV status — as being high risk and warranting testing and treatment. The guidelines further recommend testing and treating patients who are starting anti-tumor necrosis factor (TNF) treatment, receiving dialysis, or preparing for transplant surgery, as well as those with silicosis. In countries with a low incidence of TB, testing and treatment may also be considered in prisoners, health care workers, immigrants from TB-endemic countries, homeless people and people who use illicit drugs.
“Making sure everyone can obtain the treatment they need to prevent latent TB developing into active TB will save lives and reduce suffering,” Tereza Kasaeva, MD, PhD, director of WHO’s Global TB Program, said in the release.
Changes to testing recommendations
For the first time, WHO also recommends the use of both commercially available interferon-gamma release assays (IGRA) — QuantiFERON-TB Gold In-Tube (Qiagen) and T-SPOT TB (Oxford Immunotec) — in addition to tuberculin skin tests (TSTs) in resource-limited settings. In 2011, WHO released a policy statement claiming there were not enough data to confirm how IGRAs performed in low- and middle-income countries with a high TB and HIV burden. However, a more recent meta-analysis involving more than 7,700 participants showed that IGRAs were associated with a “slightly higher” predictive performance than TST, with a pooled risk ratio estimate of 2.03 (95% CI, 1.18-3.50) vs. 1.49 (95% CI, 0.79-2.80).
According to Lee Reichman, MD, MPH, senior advisor and founding executive director of the Global Tuberculosis Institute at the Rutgers New Jersey Medical School, TSTs often lead to false-positive results triggered by the bacille Calmette-Guérin (BCG) vaccine, which can induce antibodies that indicate TB infection.
“With TST, you end up treating people who had the vaccine when they were younger and exposing them to toxicities even though they were not actually infected,” Reichman told Infectious Disease News. “QuantiFERON uses antigens that are not in the BCG vaccine, so if someone who had BCG is examined with this test, you can be sure a positive result reflects true infection. IGRA use is a dynamite recommendation.”
However, the guidelines acknowledge that “there is no gold standard method” for diagnosing latent TB, and both TST and IGRAs are “imperfect tests” for active disease.
Alternative treatment options
When it comes to treatment, WHO maintained its existing recommendation to administer isoniazid monotherapy for 6 months in adults and children with latent TB. However, two new, shorter regimens can now be offered as an alternative to isoniazid monotherapy in countries with a high TB burden. These include rifapentine plus isoniazid — which can be given weekly for 3 months in adults and children — and rifampicin plus isoniazid — which can be administered daily for 3 months in children and adolescents aged younger than 15 years.
“These shorter regimens will help patients adhere to their treatment and complete it,” the WHO news release said.
Pillay, PhD, deputy director-general of health in South Africa, said in a statement that the new guidelines will “reinvigorate scale-up of TB prevention for high burden countries.”
“These guidelines clearly aim to be transformative and will go a long way in ensuring that no at-risk person gets left behind,” he said. – by Stephanie Viguers
WHO. Latent TB Infection: Updated and consolidated guidelines for programmatic management. http://www.who.int/tb/publications/2018/latent-tuberculosis-infection/en/. Accessed February 22, 2018.
Disclosures: Getahun is a TB/HIV and community engagement coordinator for WHO’s Global TB Program. Reichman reports no relevant financial disclosures.