Nontuberculous mycobacterial cervicofacial lymphadenitis in children; diagnostic performance of the Capilia MAC antibody Elisa test and possible portals of entry

Rationale: Diagnosing nontuberculous mycobacterial (NTM) cervicofacial lymphadenitis is difficult. Definitive diagnosis requires a positive culture or polymerase chain reaction (PCR) result. However, these diagnostic procedures must be performed on infected lymph node material. The only way to obtain this material is by excision of the infected lymph nodes or by aspirating fine needle specimens. Both procedures are generally performed under general anesthesia in children. A non-invasive pre-operative diagnostic test is desired for NTM cervicofacial lymphadenitis to overcome this burden. The Capilia mac antibody Elisa test is an in-vitro diagnostic test, which is developed to determine the levels of serum IgA to the glycopeptidolipid core of Mycobacterium avium complex (MAC) in serum samples.
The transmission route of nontuberculous mycobacteria (NTM) in cases of nontuberculous mycobacterial cervicofacial lymphadenitis in children remains largely unknown. In the literature it is suggested that direct exposure to the mucosa during eruption may be of importance, concluding that the oral cavity and oropharynx might play a role as the portal of entry. There is no evidence of another possible portal of entry and no study has yet assessed the overall oral microbial composition (microbiome) in this specific group of patients. In this study, it is hypothesized that NTM could be found in the oral cavity or oropharynx of patients with nontuberculous cervicofacial lymphadenitis. An aberrant microbiome could indicate an increased sensitivity to opportunistic infections.

Objective: This study intends to investigate the diagnostic potential of the Capilia mac antibody Elisa test in children with a clinical suspicion of NTM cervicofacial lymphadenitis.
Moreover, this study aims at investigating whether NTM possibly access the body through the oral cavity or oropharynx and if the patients carry an aberrant oral microbiome. Thus, the study will provide more insight regarding the pathophysiology of NTM cervicofacial lymphadenitis.

Study design: Prospective clinical observational study. Swabs of the tongue, tonsils and gingiva are taken from patients with suspected NTM cervicofacial lymphadenitis. Moreover, 6 mL blood samples are taken. All procedures are performed during surgery, which is the current best treatment for patients with a high clinical suspicion of NTM cervicofacial lymphadenitis. The research protocol will only be carried out in patients who already have an indication for surgery and the decision to perform surgery is made independently of the research protocol by the treating physician. Real-time PCR and culture are performed on the material obtained by the swabs to confirm the possible presence of the NTM. Real-time PCR and culture are part of routine diagnostic workup. Until now, to the best of our knowledge, this will be the first study attempting to identify nontuberculous mycobacteria in the oral cavity and oropharynx of cervicofacial lymphadenitis patients. Moreover, this is the first study to investigate the diagnostic potential of the Capilia mac antibody Elisa test in this specific patient population.

It is hypothesized that NTM could be found in the oral cavity or oropharynx of patients with nontuberculous cervicofacial lymphadenitis. An aberrant microbiome could indicate an increased sensitivity to opportunistic infections. The estimated sensitivity of the investigated diagnostic test is hypothesized to be 70% and specificity 90%.

Single visit

Swabs of the tongue, tonsils and gingiva are taken from patients with suspected NTM cervicofacial lymphadenitis. Moreover, blood samples are taken. All procedures are performed during surgery.