title: Non-tuberculous mycobacteria in children: muddying the waters of tuberculosis diagnosis.
abstract: Non-tuberculous mycobacteria (NTM) are a large family of acid-fast bacteria, widespread in the environment. In children, NTM cause lymphadenitis, skin and soft tissue infections, and occasionally also lung disease and disseminated infections. These manifestations can be indistinguishable from tuberculosis on the basis of clinical and radiological findings and tuberculin skin testing. A diagnostic and therapeutic problem for respiratory physicians and other clinicians is therefore evident, particularly in settings where childhood tuberculosis is common, and bacteriological confirmation of any mycobacterial disease is difficult because of low availability of laboratory services in low-resource settings and the inherent paucibacillary nature of mycobacterial disease in childhood. The epidemiology of NTM varies by world region, and attempts to understand the burden of NTM disease and to identify risk factors in the paediatric population are hampered by inadequate mandatory NTM reporting and the overlap of clinical presentation with tuberculosis. The immune response to both NTM and Mycobacterium tuberculosis is based on cellular immunity and relies on the type-1 cytokine pathway. The disruption of this immune response by genetic or acquired mechanisms, such as mendelian susceptibility to mycobacterial disease or HIV, might result in predisposition to mycobacterial infections. Published diagnostic and management guidelines do not provide specific advice for diagnosis of NTM in children, from whom the quantity and quality of diagnostic samples are often suboptimum. Treatment of NTM infections is very different from the treatment of tuberculosis, depends on the strain and anatomical site of infection, and often involves antibiotic combinations, surgery, or both. In this Review, we summarise the epidemiological and clinical features of NTM infection in children, with a specific focus on the implications for public health in settings with a high endemic burden of childhood tuberculosis.
authors.affiliation: Centro de Investigação em Saude de Manhiça, Maputo, Mozambique; ISGlobal, Barcelona Centre for International Health Research, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: López-Varela
authors.affiliation: Centro de Investigação em Saude de Manhiça, Maputo, Mozambique; ISGlobal, Barcelona Centre for International Health Research, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Alberto L
authors.initials: AL
authors.lastname: García-Basteiro
authors.affiliation: Unidad Enfermedades Infecciosas Pediátricas, Departamento de Pediatría, Hospital General Univesitario Gregorio Marañón, Madrid, Spain; Laboratorio Inmunobiología Molecular, Hospital General Univesitario Gregorio Marañón, Madrid, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Santiago
authors.affiliation: Center of Infectious Diseases and Travel Medicine and Center for Chronic Immunodeficiency, Freiburg University, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Wagner
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, Netherlands.
authors.forename: Jakko
authors.initials: J
authors.lastname: van Ingen
authors.affiliation: Vaccinology Theme, MRC Unit, The Gambia; Department of Paediatrics, Imperial College London, UK. Electronic address: b.kampmann@imperial.ac.uk.
authors.forename: Beate
authors.initials: B
authors.lastname: Kampmann
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001500:BCG Vaccine; D002648:Child; D002675:Child, Preschool; D017281:Cost of Illness; D003937:Diagnosis, Differential; D014943:Global Health; D054884:Host-Pathogen Interactions; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008171:Lung Diseases / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology; D008199:Lymphadenitis / Q000175:diagnosis / Q000188:drug therapy; D009165:Mycobacterium Infections, Nontuberculous / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology; D009170:Nontuberculous Mycobacteria / Q000302:isolation & purification; D012307:Risk Factors; D013183:Sputum / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D001500:BCG Vaccine