title: Nontuberculous Mycobacterial Disease in Children - Epidemiology, Diagnosis & Management at a Tertiary Center.
abstract: BACKGROUND
  There are limited data on the epidemiology, diagnosis and optimal management of nontuberculous mycobacterial (NTM) disease in children.
  
  
  METHODS
  Retrospective cohort study of NTM cases over a 10-year-period at a tertiary referral hospital in Australia.
  
  
  RESULTS
  A total of 140 children with NTM disease, including 107 with lymphadenitis and 25 with skin and soft tissue infections (SSTIs), were identified. The estimated incidence of NTM disease was 0.6-1.6 cases / 100,000 children / year; no increasing trend was observed over the study period. Temporal analyses revealed a seasonal incidence cycle around 12 months, with peaks in late winter/spring and troughs in autumn. Mycobacterium-avium-complex accounted for most cases (77.8%), followed by Mycobacterium ulcerans (14.4%) and Mycobacterium marinum (3.3%). Polymerase chain reaction testing had higher sensitivity than culture and microscopy for acid-fast bacilli (92.0%, 67.2% and 35.7%, respectively). The majority of lymphadenitis cases underwent surgical excision (97.2%); multiple recurrences in this group were less common in cases treated with clarithromycin and rifampicin compared with clarithromycin alone or no anti-mycobacterial drugs (0% versus 7.1%; OR:0.73). SSTI recurrences were also less common in cases treated with two anti-mycobacterial drugs compared with one or none (10.5% versus 33.3%; OR:0.23).
  
  
  CONCLUSIONS
  There was seasonal variation in the incidence of NTM disease, analogous to recently published observations in tuberculosis, which have been linked to seasonal variation in vitamin D. Our finding that anti-mycobacterial combination therapy was associated with a reduced risk of recurrences in patients with NTM lymphadenitis or SSTI requires further confirmation in prospective trials.
authors.affiliation: Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.|Infectious Diseases Unit, Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.|Murdoch Children's Research Institute, Parkville, Victoria, Australia.|Academic Unit of Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.|NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
authors.forename: Marc
authors.initials: M
authors.lastname: Tebruegge
authors.affiliation: Infectious Diseases Unit, Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Pantazidou
authors.affiliation: Department of Anatomical Pathology, Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.
authors.forename: Duncan
authors.initials: D
authors.lastname: MacGregor
authors.affiliation: Department of Microbiology, Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.
authors.forename: Gena
authors.initials: G
authors.lastname: Gonis
authors.affiliation: Mycobacterium Reference Laboratory, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Leslie
authors.affiliation: Department of Geography and Environment, University of Southampton, Southampton, United Kingdom.
authors.forename: Luigi
authors.initials: L
authors.lastname: Sedda
authors.affiliation: Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.|Infectious Diseases Unit, University Children's Hospital Basel, Basel, Switzerland.
authors.forename: Nicole
authors.initials: N
authors.lastname: Ritz
authors.affiliation: Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.|Infectious Diseases Unit, Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.|Murdoch Children's Research Institute, Parkville, Victoria, Australia.
authors.forename: Tom
authors.initials: T
authors.lastname: Connell
authors.affiliation: Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.|Infectious Diseases Unit, Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.|Murdoch Children's Research Institute, Parkville, Victoria, Australia.
authors.forename: Nigel
authors.initials: N
authors.lastname: Curtis
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D017291:Clarithromycin / Q000627:therapeutic use; D015331:Cohort Studies; D004269:DNA, Bacterial / Q000032:analysis / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008199:Lymphadenitis / Q000175:diagnosis / Q000453:epidemiology / Q000601:surgery; D008297:Male; D009165:Mycobacterium Infections, Nontuberculous / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology; D015269:Mycobacterium avium Complex / Q000235:genetics / Q000302:isolation & purification; D019910:Mycobacterium marinum / Q000235:genetics / Q000302:isolation & purification; D019911:Mycobacterium ulcerans / Q000235:genetics / Q000302:isolation & purification; D012189:Retrospective Studies; D012293:Rifampin / Q000627:therapeutic use; D012871:Skin Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology; D018461:Soft Tissue Infections / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology; D062606:Tertiary Care Centers
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D017291:Clarithromycin; D012293:Rifampin
references.citation: Am Rev Respir Dis. 1979 Jan;119(1):107-59
references.pmid: 369415
references.citation: Clin Infect Dis. 2007 Apr 15;44(8):1057-64
references.pmid: 17366449
references.citation: Adv Exp Med Biol. 2011;719:201-10
references.pmid: 22125046
references.citation: Eur Respir J. 2010 Jul;36(1):214-5; author reply 215-6
references.pmid: 20595171
references.citation: Pediatr Infect Dis J. 1999 Nov;18(11):968-70
references.pmid: 10571431
references.citation: Tuber Lung Dis. 1995 Aug;76(4):300-10
references.pmid: 7579311
references.citation: Clin Infect Dis. 2004 Aug 15;39(4):450-6
references.pmid: 15356803
references.citation: Lancet Infect Dis. 2013 Jan;13(1):77-88
references.pmid: 23257233
references.citation: Appl Environ Microbiol. 2007 Aug;73(15):4733-40
references.pmid: 17526786
references.citation: J Infect Dis. 2000 Jun;181(6):2099-102
references.pmid: 10837203
references.citation: J Pathol Bacteriol. 1948 Jan;60(1):93-122
references.pmid: 18876541
references.citation: Pediatrics. 2003 Nov;112(5):e434
references.pmid: 14595089
references.citation: Int J Infect Dis. 2010 Sep;14 Suppl 3:e305-6
references.pmid: 20541959
references.citation: Paediatr Child Health. 2010 May;15(5):276-82
references.pmid: 21532791
references.citation: Am J Respir Crit Care Med. 2007 Feb 15;175(4):367-416
references.pmid: 17277290
references.citation: Pediatr Infect Dis J. 2010 Aug;29(8):772-4
references.pmid: 20661106
references.citation: Am J Respir Crit Care Med. 2003 Mar 15;167(6):828-34
references.pmid: 12433668
references.citation: Pediatr Infect Dis J. 2009 Jul;28(7):642-4
references.pmid: 19561429
references.citation: Lancet. 2010 Feb 20;375(9715):664-72
references.pmid: 20137805
references.citation: Lancet Respir Med. 2015 Mar;3(3):244-56
references.pmid: 25773213
references.citation: Am Rev Respir Dis. 1989 Jan;139(1):4-7
references.pmid: 2912355
references.citation: J Clin Microbiol. 2008 Feb;46(2):618-26
references.pmid: 18057130
references.citation: ORL J Otorhinolaryngol Relat Spec. 1995 Jan-Feb;57(1):36-8
references.pmid: 7700608
references.citation: Lancet. 2004 Oct 30-Nov 5;364(9445):1613-4
references.pmid: 15519633
references.citation: Pediatr Infect Dis J. 2009 Sep;28(9):801-5
references.pmid: 19636280
references.citation: Int J Pediatr Otorhinolaryngol. 2010 Apr;74(4):343-6
references.pmid: 20163879
references.citation: J Clin Microbiol. 2005 Jul;43(7):3467-70
references.pmid: 16000480
references.citation: Eur Respir J. 2009 Oct;34(4):921-5
references.pmid: 19386690
references.citation: Arch Dis Child. 1986 Apr;61(4):368-71
references.pmid: 3707188
references.citation: Respirology. 2013 Aug;18(6):983-8
references.pmid: 23627546
references.citation: Arch Dis Child. 1995 Jun;72(6):516-7
references.pmid: 7618936
references.citation: Clin Endocrinol (Oxf). 2012 Oct;77(4):515-23
references.pmid: 22469273
references.citation: Tuber Lung Dis. 1996 Feb;77(1):43-6
references.pmid: 8733413
references.citation: J Infect. 2015 Jul;71(1):9-18
references.pmid: 25727993
references.citation: Thorax. 2007 Aug;62(8):661-6
references.pmid: 17311842