TB UPDATE
AAP's changes to TB recommendations important for pediatricians to know
Jeffrey R. Starke
"Neither IGRAS nor the skin test are perfect, and you still have to use clinical judgement, especially if you are evaluating a sick child that you are concerned might have TB,” Starke said. “Even if you have a negative IGRA or skin test, you can never rule out TB disease.”
The AAP’s tuberculosis diagnosis and treatment guidelines in the 2018 Red Book have been updated to reflect recent developments in the field, according to a presentation at the Annual Infectious Diseases in Children Symposium.
Jeffrey R. Starke, MD, professor of pediatrics at Baylor College of Medicine, said that until 2013, there was no estimate of how many children around the world were infected with TB. Once modeling studies were conducted, WHO initially estimated that approximately 500,000 to 600,000 cases occurred in children annually. In 2017, the agency increased that number to 1 million, with 230,000 deaths.
"We are fortunate in the United States that we have about 9,200 cases of TB annually, and we have a pretty low number of actual TB cases in children aged younger than 15 years," Starke said.
He added that TB has a global mortality rate of 23% — the same level of mortality observed in the pre-chemotherapy treatment era. Because effective TB treatments are available, Starke suggested that children are going undiagnosed, leading to higher mortality rates.
A study published in the International Journal of Tuberculosis and Lung Disease found that when left untreated, children aged 1 year and younger with latent TB have a 50% chance of developing active disease. Starke said that the sensitivity of a test for children aged younger than 2 years is crucial, and as children age, specificity becomes increasingly important in preventing overdiagnosis of infection and unnecessary treatment.
In the 2018 Red Book, the AAP recommends using IGRAs and has changed their treatment regimen and dosing recommendations, according to a presentation at the Annual Infectious Diseases in Children Symposium.
Starke cited a study recently published in Thorax that found that a skin test performed "a little better than a coin flip" in predicting those with latent TB infection.
For immunocompetent children, the 2018 Red Book suggests using interferon-gamma release assays (IGRAs) for children aged 2 years and older in instances when a skin test would normally be used, although some experts suggest that you can use IGRAs for patients aged 1 year and older. Previous recommendations only allowed children aged 5 years and older to be tested using IGRAs.
Neither IGRAS nor the skin test are perfect, and you still have to use clinical judgement, especially if you are evaluating a sick child that you are concerned might have TB,” Starke said. "Even if you have a negative IGRA or skin test, you can never rule out TB disease."
The 2018 Red Book also changed treatment recommendations from 9 months of daily isoniazid to 12 doses of once-weekly isoniazid/rifapentine. Previously, the 12-dose treatment was to be considered only when "the likelihood of completing another regimen is low."
If the AAP’s recommended treatment in the Red Book is not preferred by the physician or the patient, they can then consider 4 months of daily rifampin treatment. Nine months of treatment with daily isoniazid is the least preferred treatment method.
I can tell you that we give almost no one 9 months of daily isoniazid," Starke said. "The only people we give this medication to are those who cannot take the preferred options because of interactions with other medications. Everybody else is on the 12 doses of once-weekly isoniazid/rifapentine or 4 months of daily rifampin."
Furthermore, dosing recommendations have been updated in the 2018 Red Book, with standard treatment increasing from 10 to 20 mg/kg per day to 15 to 20 mg/kg per day. Infants, toddlers and patients of any age with Mycobacterium tuberculosis infection may receive 20 to 30 mg/kg per day.
References: Starke JR. New guidance for tuberculosis infection diagnosis and management - 2018. Presented at: Annual Infectious Diseases in Children Symposium; Nov. 17-18, 2018; New York.
Marais BJ, et al. Int J Tuberc Lung Dis. 2004;8:392-402.
Stout JE, et al. Thorax. 2018;doi:10.1136/thoraxjnl-2018-211715.
Interferon-γ Release Assay Performance for Tuberculosis in Childhood
BACKGROUND: Interferon-γ release assays (IGRAs) are important adjunctive tests for diagnosing tuberculosis (TB) disease in children.
METHODS: We analyzed California TB registry data for patients ≤18 years with laboratory-confirmed TB disease during 2010–2015 to identify case characteristics associated with test selection and performance and measure IGRA sensitivity.
RESULTS: In total, 778 cases of TB were reported; 360 were laboratory confirmed. Indeterminate IGRAs were associated with being <1 year old (prevalence rate ratio 9.23; 95% confidence interval 2.87 to 29.8) and having central nervous system disease (prevalence rate ratio 2.69; 95% confidence interval 1.06 to 6.86) on multivariable analysis. Ninety-five children had both an IGRA and tuberculin skin test (TST) performed. Among those, the sensitivity of IGRA in 5- to 18-year-olds was 96% (66 out of 69) vs 83% (57 out of 69) for TST (P = .01); IGRA sensitivity compared with TST in children ages 2 to 4 was 91% (10 out of 11) vs 91% (10 out of 11) (P > .99), and the sensitivity compared with TST in children aged <2 years was 80% (12 out of 15) vs 87% (13 out of 15) (P > .99).
CONCLUSIONS: This is the largest North American analysis of IGRA use and performance among children with TB disease. In children <5 years old, IGRA sensitivity is similar to TST, but sensitivity of both tests are reduced in children <2 years old. Indeterminate results are higher in children <1 year old and in central nervous system disease. In children ≥5 years old with laboratory-confirmed TB, IGRA has greater sensitivity than TST and should be considered the preferred immunodiagnostic test..
(Reference: Pediatrics. 2018 Jun;141(6). pii: e20173918. doi: 10.1542/peds.2017-3918.)
CDC expands treatment recommendation for latent TB to younger children
The CDC has expanded its recommendation of a short-course combination regimen of once-weekly isoniazid and rifapentine for the treatment of latent tuberculosis infection to include children aged 2 to 11 years and patients with HIV/AIDS taking antiretroviral medications.
Children with latent tuberculosis infection (LTBI) should be treated to prevent them from developing active TB disease, according to health officials. However, the CDC’s recommendations from 2011 limited the use of the shortest regimen currently available - once-weekly isoniazid and rifapentine for 12 weeks (3HP), Andrey S. Borisov, MD, medical epidemiologist at the CDC’s Division of Tuberculosis Elimination, told Infectious Diseases in Children.
"At that time, not enough data were available to recommend 3HP for children under 12 years old, persons living with HIV/AIDS and taking antiretroviral therapy, or as a self-administered therapy," he said.
A CDC Work Group, which included epidemiologists, health scientists, physicians from the CDC’s Tuberculosis Elimination Program and a CDC library specialist, conducted a meta-analysis of 19 articles, which included 15 unique studies. The target population included persons aged at least 12 years, children aged 2 to 11 years or people living with HIV.
The researchers found that 3HP was as safe and effective as other LTBI treatment regimens in the target populations.
Based on the findings, the CDC continues its recommendation of 3HP for treating LTBI in adults. However, new recommendations by the CDC include the use of 3HP for patients aged 2 to 17 years and patients with HIV infection, including AIDS, and are taking antiretroviral medications with acceptable drug-drug interactions with rifapentine. The recommendations also include using 3HP by self-administered therapy or directly observed therapy in patients aged at least 2 years.
The researchers also provided guidance to health care providers on the use of 3HP treatment for LTBI, including:
- evaluating all patients for active TB before and during treatment;
- informing patients or parents of possible adverse effects;
- ordering baseline hepatic chemistry blood tests for patients with certain conditions, including HIV, liver disorder, postpartum period of 3 months or less after delivery, regular alcohol use, injection drug use, or use of medications with known possible interactions; and
- conducting blood tests for patients whose baseline testing is abnormal and for patients who are risk for liver disease.
"Pediatricians should work with parents or legal guardians to determine the best treatment plan and to provide support and resources to help patents complete treatment successfully,” Borisov said. “CDC encourages clinicians and public health professionals to review and implement the updated recommendations, which include guidance on patient education and monitoring.” – by Bruce Thiel
(Source: Borisov AS, et al. MMWR. 2018; doi:10.15585/mmwr.mm6725a5.)