Infants and young children with TB frequently have extrapulmonary manifestations such as meningitis, says Samir S. Shah, MD, MSCE, pediatric hospitalist and pediatric infectious disease specialist at the Children’s Hospital of Philadelphia.
Extrapulmonary tuberculosis is more likely among foreign-born individuals, even if they have been in the U.S. for five years or longer. This phenomenon also occurs among the elderly and immunocompromised patients, including those receiving corticosteroid therapy.
A negative PPD skin test rules out tuberculosis. A PPD can easily be falsely negative, says Dr. Swanson. “In fact, among normal adults, probably 25% of all cases of active pulmonary tuberculosis will have a negative PPD, even when their sputum demonstrates acid-fast bacilli,” he says. “The incidence of a false-negative PPD is even higher in children, and also higher if it is extrapulmonary tuberculosis. In half of these children with extrapulmonary tuberculosis you may easily have a falsely negative PPD.”
With that said, hospitalists should approach TB treatment while being mindful of these caveats:
Because tuberculosis may be extrapulmonary, it may not be identified with a chest X-ray. Almost every organ structure and body site can be a site of infection for tuberculosis, including the central nervous system, pericardium, bone, joints, skin, lymph nodes, and gastrointestinal tract.
Whether tuberculosis bacilli can be detected in sputum is a key determinant of transmissibility. “The reality is that Andrew Speaker, as it turns out, was smear negative, so they didn’t see any organisms with acid-fast stains,” says Dr. Shah. “[But] if individuals are smear-negative, they are they are still capable of transmitting disease.”
If you encounter a pediatric case of tuberculosis, transmission most likely has occurred from a household contact. Up to 17% of new cases of tuberculosis came from contact with someone with a negative acid-fast bacilli smear. If a sputum sample contains fewer than 1,000 bacteria/mL, the organism may not be detected on acid-fast staining, but still hold enough tuberculous bacilli to infect a person, especially with close and prolonged exposure. It takes only one to five bacilli arriving at the terminal pulmonary alveolus to infect an individual.
“We believe that roughly one-third to two-thirds of people exposed to a smear-positive individual with pulmonary tuberculosis will become infected,” says Dr. Swanson. “Although most will develop only latent tuberculosis infection, some will progress to active disease, particularly infected infants and young children.”
Because young children do not produce sputum, TB diagnosis in children is problematic. Infected children will present with malaise, fever, failure to thrive, and possibly erythema nodosum. Presentation is atypical: cough is infrequent except with endobronchial disease.
“One has to have a low index of suspicion and actively look for tuberculosis in children,” says Dr. Swanson.
Using gastric aspirates is one method, but is probably not more than 50% sensitive. The test is not ideal because it is time consuming, uncomfortable for young children, and aspirate samples must be collected on three consecutive early mornings.
Other approaches include ultrasound-guided transesophageal biopsies or computed tomography (CT)-guided biopsies of primarily hilar or paratracheal lymph nodes evident on CT.
There are also molecular diagnostic methods. In older children and adolescents, hospitalists can collect sputum induced with hypertonic saline. Even when acid-fast stains are negative, PCRs can be used to rapidly detect the presence of M. tuberculosis complex in sputum samples, tissue samples, and gastric aspirates, and stool samples when looking for intestinal tuberculosis.
The QuantiFERON TB Gold test (Cellestis International) is used to measure the interferon gamma released when blood samples are mixed with TB antigens and incubated. Although it has been around a number of years, it has just been incorporated into practice in the past two. The test is highly sensitive and specific but does not distinguish active from latent infection.