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Letter
"Mycobacterium tilburgii"
Infections
Dirk Wagner,*
Margreet C. Vos,†‡ Anton G.M. Buiting,‡ Annerose Serr,* Anneke M.C. Bergmans,§
Winfried V. Kern,* and Leo M. Schouls¶
*University Hospital, Freiburg, Germany; †Erasmus University Medical Center,
Rotterdam, the Netherlands; ‡St Elisabeth Hospital, Tilburg, the Netherlands;
§Franciscus Hospital, Roosendaal, the Netherlands; and ¶National Institute
of Public Health and the Environment, Bilthoven, the Netherlands
Suggested
citation for this article
To the Editor: Advanced molecular biologic methods have improved
the species differentiation and taxonomic classification of microorganisms,
including nontuberculous mycobacteria. Identifying and characterizing
an increasing number of "new" mycobacterial species of medical
importance is now possible. Often, these newly described mycobacteria
have been isolated from immunocompromised patients (1,2).
Some of those have been difficult to cultivate, and 16S rRNA gene sequencing
or similar methods have become of major importance to allow species identification
and clinical diagnosis. Here, we report 2 patients with disease likely
caused by a novel mycobacterial species that could not been previously
cultivated. Diagnosis relied on molecular identification of acid-fast
organisms in tissues. We also briefly review 2 similar cases published
previously and note that all 4 known patients were from central Europe.
A 43-year-old woman without evidence of immunodeficiency reported recurrent
episodes of dysuria, hematuria, and abdominal discomfort for >1 year.
On cystoscopy, a hyperemic bladder with yellow plaques was observed. Biopsy
of the plaques showed granulomatous infiltration of histiocytes. No definite
diagnosis was made, and symptomatic relief occurred after a trial of empiric
antimicrobial drug therapy. When the patient sought treatment again with
persistent abdominal discomfort, endoscopy showed a lesion in the stomach
that resembled a healed ulcer and numerous elevated yellow plaques throughout
the colon and ileum. Microscopically, a granulomatous inflammation with
macrophages filled with many acid-fast rods was seen, but mycobacterial
growth did not occur in different media or in a guinea pig. Antituberculous
treatment was initiated, and the patient slowly improved. A repeat colonoscopy
showed fewer and smaller lesions. Efforts to culture the organism from
biopsy specimens were again unsuccessful (different solid and liquid media,
blood or chocolate agar, guinea pig, Balb/c mice). Sequencing of polymerase
chain reaction (PCR) products of the 16S rRNA gene (3)
from the organism represented a previously unknown mycobacterial species
(EMBL DNA database: accession number Z50172). "Mycobacterium tilburgii"
was proposed as the designation of this species because the novel mycobacterium
was identified in the city of Tilburg (4). Retrospective
analysis of the initial bladder biopsy specimen and of 2 lymph nodes taken
during abdominal surgery (which became necessary because of a complicating
ileal obstruction) confirmed the presence of "M. tilburgii"
16S rRNA gene sequences. All samples yielding PCR fragments hybridized
with a "M. tilburgii"–specific biotinylated DNA
probe.
A 34-year-old AIDS patient sought treatment for involuntary weight loss.
Endoscopy showed white superficial embossments of the duodenal mucosa.
Biopsy specimens were negative for acid-fast bacteria and mycobacterial
growth (again, different solid and liquid media, extended incubation periods).
Antiretroviral therapy was begun, but asthenia, persistent fever, diarrhea,
vomiting, and cachexia developed. Repeat endoscopy showed yellow, plaquelike
lesions in the duodenum (Appendix Figure) and esophagus
with periodic acid–Schiff (PAS) and acid-fast intracellular bacteria that
were nonculturable. PCR of 16S rRNA gene (3) confirmed
the presence of mycobacterial DNA; sequencing showed 100% homology to
the species with the proposed name "M. tilburgii" (4).
Retrospectively, "M. tilburgii"16S rRNA was present
in the initial duodenal biopsy specimen, when no mycobacteria were detected
microscopically. Combination therapy led to a gradual disappearance of
fever and diarrhea. The patient's weight increased, and the lesions disappeared
(Table). Control endoscopy results were unremarkable,
although duodenal biopsy specimens showed PAS-positive material. Mycobacterial
DNA was no longer detectable.
We believe that the identified acid-fast organism named "M.
tilburgii" was the causative agent of illness in the 2 patients.
First, the clinical and histopathologic appearance of the lesions is compatible
with mycobacterial infection. Second, the finding that the macrophages
in these lesions contained large numbers of acid-fast bacteria supports
the conclusion that mycobacterial infection caused the lesion. Third,
the involvement of normally sterile locations such as lymph nodes, and
the improvement after antimycobacterial therapy with disappearance of
the lesions, acid-fast organisms, and mycobacterial DNA supports a causative
role of the organism rather than a bystander role.
Attempts to culture the organism from biopsy specimens and resection
materials remained unsuccessful, although specific requirements for organisms
like M. genavense, a mycobacterium that also is not cultivable
on regular mycobacterial media (5), were met.
Diagnosis therefore had to rely on sequencing of PCR products. Based on
16S rRNA homology, "M. tilburgii" shows close
relationship to M. sherrisii, a M. simiae–related
mycobacterium (6) that probably corresponds to
Mycobacterium strain IWGMT 90143 (accession no. X88906) (7).
"M. tilburgii" also has a high homology to Mycobacterium
sp. Murphy, a mycobacterial species that is considered the cause of canine
lepra and that also has not been cultivated so far (8)
(accession no. AF144747).
These 2 patients double the number of patients reported previously (Table).
Both previously reported M. tilburgii patients had AIDS, 1 of whom
had a disease similar to that of the second patient in this report (9).
Taken together, 3 patients had gastrointestinal involvement with yellow
mucosal plaques (Appendix Figure), and 1 patient
had pulmonary nodules (10). One of the 4 patients
did not have a detectable immunodeficiency, yet had gastrointestinal and
urinary bladder lesions. Although complications occurred, treatment was
successful in all 4 cases with usual anti–Mycobacterium avium complex
therapy. Interestingly, all 4 patients so far are of middle-European descent.
This species may be geographically confined, similar to the occurrence
of M. malmoense in which most clinical isolates come from
northern Europe (1).
References
- Brown-Elliott BA, Griffith DE, Wallace RJ Jr. Newly
described or emerging human species of nontuberculous mycobacteria.
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identification of mycobacteria by nucleic acid sequence determination:
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Table. Characteristics
of patients with confirmed "Mycobacterium tilburgii"
disease*
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Sex (age, y)
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Immuno-suppression
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CD4 count (cell/μL)
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Disease manifestation
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Treatment (duration, mo)
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Diagnosed in
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Reference
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F (45)
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No
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Normal
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Bladder, intestinal lymphnodes, stomach,
ileum, colon
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Pyrazinamide, isoniazid, rifampin (5);
ethambutol, ciprofloxacin, clarithromycin, rifampin (11); surgical
resection
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The Netherlands
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This study
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M (34)
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AIDS
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37
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Esophagus, duodenum
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Ethambutol, clarithromycin, rifabutin
(5)
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Germany
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This study
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M (35)
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AIDS
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20
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Duodenum, abdominal lymph nodes
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Ethambutol, clarithromycin, rifabutin
(12†)
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Germany
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(9)
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M (41)
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AIDS
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17
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Pulmonary nodules
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Surgical resection; ethambutol, ciprofloxacin,
clarithromycin (6); ethambutol, clarithromycin (12‡)
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Germany
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(10)
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*F, female; M, male.
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†6 weeks ineffective.
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‡ Ongoing.
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Suggested citation
for this article:
Wagner D, Vos MC, Buiting
AGM, Serr A, Bergmans AMC, Kern WV, et al. "Mycobacterium tilburgii"
infections [letter]. Emerg Infect Dis [serial on the Internet]. 2006 Mar
[date cited]. Available from http://www.cdc.gov/ncidod/EID/vol12no03/05-1139.htm
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