Tuberculosis: What to do and when to call for help

While tuberculosis is not something all pediatricians see in daily practice, it remains a threat in some populations, and pediatricians should be aware of the risk factors and diagnostic recommendations.

Deborah A Lewinsohn, MD, FAAP, professor of Pediatrics and head of the Division of Infectious Disease at Oregon Health and Science University, Portland, provided an overview of the risk factors for tuberculosis in children, as well as diagnostic tests and treatment, at the American Academy of Pediatrics (AAP) 2017 National Conference and Exhibition on Saturday, September 16.

Her session titled "TB or not TB? Who to test, how to test, and what to do?" covered a variety of concerns for both active and latent tuberculosis. Although she presented no original research at the session, Lewinsohn says it provided important reminders about tuberculosis management.

"This is about what primary care providers need to know about diagnosing and treating latent tuberculosis infection, diagnosing tuberculosis, and when to refer to a tuberculosis specialist," Lewinsohn says. "This information is derived largely from clinical practice guidelines and, in some part, from my expert opinion."

Childhood tuberculosis is a progressive condition with a lifetime risk of reactivation of the disease. There were 9278 new cases of tuberculosis in the United States as of March 2017, according to Lewinsohn, and prevalence of latent tuberculosis infection was 4.4% to 4.8%. Sixty-eight percent of the cases were reported in foreign-born individuals, she says.

Risk factors for tuberculosis infection include living in congregate settings and homelessness, Lewinsohn says, and latent tuberculosis is most common among foreign-born individuals and those who have been in close contact with other persons with tuberculosis. Risk should be assessed every 6 months for the first year an individual is in this country, and ideally every year after that, she says.

Questions that may be included in an assessment cover whether the patient has had contact with individuals or has family members with tuberculosis; if a family member had a positive tuberculin skin test; if a child was born in a high-risk country; or if the patient has traveled to a high-risk country with contact with resident populations for more than a week.

Some signs of tuberculosis infection in children may include weight loss or poor weight gain, growth delays, night sweats, chills, or cough. A chest X-ray may reveal lymphadenopathy of the hilar, subcarinal, paratracheal, or mediastinal nodes; atelectasis; infiltrate of a segment or lobe; pleural effusion; or interstitial cavities.

Children with tuberculosis have the disease manifest in different forms with different symptoms. In children with scrofula, there is commonly an extrapulmonary manifestation, a firm and fixed unilateral neck mass with shiny erythema that spreads to the lymph nodes; low-grade fever; and otherwise mild systemic symptoms. In children with osteomyelitis, children may present most commonly with vertebral osteomyelitis and back pain with unusual positioning or refusal to walk. They may also have a low-grade fever. In children with pericarditis, symptoms may include a low-grade fever, weight loss, and cough with progression to constriction lung sounds and friction rub, distant heart sounds, and pulsus paradoxus.

Children with meningitis will have insidious symptoms that may last for weeks, Lewinsohn says. During the first stage of infection, parents may notice a personality change, irritability, anorexia, and fever. During stage 2, these symptoms progress to include increased cranial pressure and the symptoms that accompany it. By stage 3, the child will experience severe neurologic damage including coma and autonomic instability.

In active tuberculosis, interferon-gamma release assays (IGRAs) do not accurately identify infection for children in endemic regions, although they are more useful in low-prevalence areas. Cultures are most likely to be positive in the youngest children at highest risk of tuberculosis, with cultures positive in up to 50% of children. Early morning aspirate should be collected on 3 separate days for this testing, Lewinsohn notes.

Testing for latent tuberculosis infection should occur for all individuals who have had contact with someone with confirmed or suspected tuberculosis, or for those who have immigrated from or recently traveled to countries with endemic tuberculosis. Annual testing should occur for anyone with HIV, and initial or periodic testing is recommended for any children with an increased risk of exposure, or for those with diabetes, chronic renal failure, immunodeficiencies, or malnutrition. Testing should also occur before initiation of any type of immunosuppressive therapies, according to Lewinsohn.

Diagnosis can be done through a few methods, one being the purified protein derivative (PPD) skin test. For this method, 5 tuberculin units are injected into the skin and assessed for induration after 48 to 72 hours. The problem with this method of testing, Lewinsohn says, is that readings can have various results and require a return visit. There is a low positive predictive value in countries with low prevalence, a good probability of a false negative, and confusing cutoff levels for different risk groups. Testing through IGRAs may offer a better diagnosis, as they are specific to the Mycobacterium tuberculosis complex. This method of testing also does not require a return visit, and results are less variable with 1 cutoff point.

According to AAP guidelines, tuberculin skin testing is preferred to IGRA in children aged younger than 5 years for latent tuberculosis, whereas IGRA is preferred in children aged older than 5 years. If a child has a negative skin test, an additional IGRA test should be considered if the individual is suspected to have tuberculosis or is in a high-risk group. If a skin test is positive, IGRA is also considered in cases where the child is healthy or to rule out nontuberculous mycobacteria. Any IGRA testing that comes back indeterminate is not interpretable and should be repeated, Lewinsohn notes.

Tuberculosis should be ruled out prior to initiating therapy for latent tuberculosis infection, and a pediatric tuberculosis expert also should be consulted.

Treatment for latent tuberculosis includes isonicotinylhydrazide (INH) daily for 9 months for INH-susceptible strains, or daily rifampin for 4 months for INH-resistant/rifampin-susceptible strains. A specialist should be consulted for treatment options if the child has INH-resistant and rifampin-resistant tuberculosis. A short course of INH and rifapentine may also be used once a week for 12 weeks. This option is recommended mainly for children aged older than 12 years and should be given in cooperation with a local health department.

Lewinsohn says she hopes clinicians will take away from her session a better understanding of how to use both skin tests and IGRAs in the diagnosis of latent tuberculosis, with skin tests preferred in children aged younger than 5 years and IGRA preferred in children aged older than 5 years.