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Mycobacterium avium infections in children
Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Mycobacterium avium belongs to a group of over 130 species of non-tuberculous mycobacteria (NTM) or environmental mycobacteria. The subspecies Mycobacterium avium avium was originally described as the causative agent of bird tuberculosis, but was later found to cause disease also in humans. Small children display a special form of infection that is seldom detected in other age groups. It manifests as a chronic lymphadenitis usually in the head and neck region. The incidence rate is approximately 1-5/100,000 children/year. However, exposure to this bacterium is high as judged by sensitin skin test studies. Even if a lot of persons are infected with M. avium, a majority of them do not develop disease and the bacterium is therefore considered to be of low virulence, causing disease mainly in immunocompromised persons. Children with M. avium lymphadenitis, however, usually do not have any known deficiencies in the immune system.

This thesis elucidates why small children are prone to develop disease by M. avium. Investigation of a possible zoonotic spread of this bacterium to children involved analysis and comparison of different strains isolated from birds and other animals and from children, using the restriction fragment length polymorphism (RFLP) method on insertion sequence IS1245, resulting in the finding that the children were infected exclusively with the new proposed subspecies M. avium hominissuis. Animals in general and birds in particular were infected with the subspecies M. avium avium (using the more narrow definition). Moreover, when investigating the immunological response of human peripheral blood mononuclear cells (PBMCs) to stimulation with M. avium hominissuis and M. avium avium, respectively, it was found that the former subspecies induced lower IFN-γ and IL-17 than the latter, but higher levels of Il-10, which might contribute to explain the higher pathogenicity of M. avium hominissuis in humans.

Through studies of the geographical distribution of cases of M. avium infection in children in Sweden and the seasonal variation of the disease, a fluctuation of the incidence over the year was detected, with higher numbers of cases in the autumn months and lower numbers in the late spring. There was a higher incidence rate in children living close to water than in those living in the inland or in the urban areas. Therefore, outdoor natural water is the most probable source of infection in children with M. avium lymphadenitis. Through a descriptive clinical retrospective study, complete surgical removal of the affected lymph node was found to lead to better results than treatment by incision and drainage of abscess or expectation only.

Finally there might be several explanations as to why an individual develops disease after infection with M. avium, such as, exposure, bacterial virulence factors or possible specific deficiencies of the immune system of the host or a combination of these factors. Which are the more important factors regarding children with M. avium lymphadenitis is still an open question.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press , 2009. , 76 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1130
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-53786ISBN: 978-91-7393-623-1 (print)OAI: oai:DiVA.org:liu-53786DiVA: diva2:291882
Public defence
2009-05-29, Fullriggaren, Kalmar Högskola, Kalmar, 13:00 (English)
Opponent
Supervisors
Available from: 2010-02-03 Created: 2010-02-03 Last updated: 2010-02-03Bibliographically approved
List of papers
1. Mycobacterium avium with the bird type IS1245 RFLP profile is commonly found in wild and domestic animals, but rarely in humans
Open this publication in new window or tab >>Mycobacterium avium with the bird type IS1245 RFLP profile is commonly found in wild and domestic animals, but rarely in humans
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2005 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 37, no 1, 15-20 p.Article in journal (Refereed) Published
Abstract [en]

Cervical lymphadenitis is the main manifestation of Mycobacterium avium infection in immunocompetent children. Exposure to birds has been discussed as a source of infection. To clarify from where children acquire the infection, M. avium isolates from different origins were analysed with restriction fragment length polymorphism (RFLP) on insertion sequence IS1245, and compared by computer cluster correlation analysis. This molecular epidemiological tool has previously revealed a distinction between multiband profiles found mainly in strains from humans, and a 3-band/bird type profile in strains isolated mainly from birds. 32 isolates from children were compared with 28 isolates from adults and 45 isolates from animals. We found that 67% of the animal isolates had the bird type profile, also found in 1 sputum isolate from an adult. Strains from children showed only multiband profiles that did not differ significantly from profiles of isolates from adults. All but 2 bird isolates showed the bird type profile. Neither of the remaining 2, which had multiband profiles, clustered with the isolates from children. Our results indicate that the true reservoir of M. avium. is unknown. Thus the question of whether or not M. avium can be incriminated as a zoonotic disease remains unanswered. © 2005 Taylor & Francis.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-37021 (URN)10.1080/00365540510026850 (DOI)33487 (Local ID)33487 (Archive number)33487 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
2. Mycobacterium avium lymphadenopathy among children, Sweden
Open this publication in new window or tab >>Mycobacterium avium lymphadenopathy among children, Sweden
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2008 (English)In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 14, no 4, 661-663 p.Article in journal (Refereed) Published
Abstract [en]

We studied Mycobacterium avium lymphadenopathy in 183 Swedish children (<7 years of age) from 1998 through 2003. Seasonal variation in the frequency of the disease, with a peak in October and a low point in April, suggests cyclic environmental factors. We also found a higher incidence of the disease in children who live close to water.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-44944 (URN)10.3201/eid1404.060570 (DOI)78351 (Local ID)78351 (Archive number)78351 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
3. Clinical features and incidence of Mycobacterium avium infections in children
Open this publication in new window or tab >>Clinical features and incidence of Mycobacterium avium infections in children
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2008 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 40, no 6-7, 481-486 p.Article in journal (Refereed) Published
Abstract [en]

Mycobacterium avium is the most common pathogen in children presenting as non-tuberculous mycobacterial lymphadenitis. In Sweden non-tuberculous mycobacterial infection is a notifiable disease. The goal of our study was to determine the annual incidence of M. avium infection in Swedish children, 1998-2003, and describe clinical features related to age and treatment of children with M. avium lymphadenitis. To do this, we retrospectively analysed patient records of 162 children less than 7 y of age from the entire country with culture-verified M. avium disease. The incidence of M. avium infection in Sweden was lower in 2000-2003 than in 1998-1999. Young children (≤24 months old) had more constitutional symptoms at onset of disease than older children. One-third of the children had received 2 or more antibiotic courses before diagnosis. Disfiguring scars after healing were more common in children who were not treated with surgical extirpation of the affected lymph nodes. The decreasing incidence of M. avium infection among Swedish children in recent y is in contrast to reports of increasing non-tuberculous mycobacterial disease from other countries. Our results support the view that M. avium lymphadenitis should be treated by surgical removal of the affected tissue.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-44945 (URN)10.1080/00365540701840088 (DOI)78352 (Local ID)78352 (Archive number)78352 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
4. Mycobacterium avium avium and Mycobacterium avium hominissuis give different cytokine responses after in vitro stimulation of human blood mononuclear cells
Open this publication in new window or tab >>Mycobacterium avium avium and Mycobacterium avium hominissuis give different cytokine responses after in vitro stimulation of human blood mononuclear cells
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2012 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 4, e34391- p.Article in journal (Refereed) Published
Abstract [en]

Background: Mycobacterium avium is the principal etiologic agent of non-tuberculous lymphadenitis in children. It is also a known pathogen for birds and other animals. Molecular epidemiologic evidence indicates that humans and animals are infected with different M. avium subspecies, namely, M. avium subsp. avium and M. avium subsp. hominissuis, respectively.

Aim: To investigate the effect on the human immune system of 10 isolates of M. avium subsp. avium mainly isolated from animals and of 11 isolates of M. avium subsp. hominissuis isolated from children with lymphadenitis.

Method: Peripheral blood mononuclear cells (PBMC) from six healthy blood donors were stimulated in vitro with the inactivated mycobacteria followed by quantification of IL-10, IL-12p70, TNF, IFN-γ and IL-17 in supernatants by multiplex bead array analysis (Luminex).

Results: M. avium subsp. hominissuis induced significantly more IL-10 and significantly less IL-12p70, TNF, IFN-γ and IL-17 compared to M. avium subsp. avium. All strains induced high levels of IL-17, but very little IL-12.

Conclusion: The lower T helper (Th) 1 and Th17 responses induced by M. avium subsp. hominissuis compared to M. avium subsp. avium after in vitro stimulation of PBMC might contribute to its higher pathogenicity in humans.

Place, publisher, year, edition, pages
PloS, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-53785 (URN)10.1371/journal.pone.0034391 (DOI)000305297500026 ()
Available from: 2010-02-03 Created: 2010-02-03 Last updated: 2017-12-12

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