"Mycobacterium tilburgii" infections.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 mycobacterial
emanating from or pertaining to mycobacterium.
may be caused by Mycobacterium tuberculosis (see cutaneous tuberculosis), M. species of medical importance is now possible. Often, these newly described mycobacteria have been isolated from immunocompromised immunocompromised /im·mu·no·com·pro·mised/ (-kom´pro-mizd) having the immune response attenuated by administration of immunosuppressive drugs, by irradiation, by malnutrition, or by certain disease processes (e.g., cancer). 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 dysuria /dys·uria/ (dis-u´re-ah) painful or difficult urination.dysu´ric
Difficult or painful urination. , hematuria hematuria
Blood in the urine. It usually indicates injury or disease of the kidney or another structure of the urinary system or possibly, in males, the reproductive system. It may result from infection, inflammation, tumours, kidney stones, or other disorders. , and abdominal discomfort for >1 year. On cystoscopy Cystoscopy Definition
Cystoscopy (cystourethroscopy) is a diagnostic procedure that is used to look at the bladder (lower urinary tract), collect urine samples, and examine the prostate gland. , a hyperemic hyperemic,
adj having a large volume of blood in any given place in the body. bladder with yellow plaques was observed. Biopsy of the plaques showed granulomatous granulomatous /gran·u·lom·a·tous/ (-lom´ah-tus) containing granulomas.
Resembling a tumor made of granular material. 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 ileum: see intestine.
Final and longest segment of the small intestine. It is the site of absorption of vitamin B12 (see vitamin B complex) and reabsorption of about 90% of conjugated bile salts. . 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 polymerase chain reaction (pŏl`ĭmərās') (PCR), laboratory process in which a particular DNA segment from a mixture of DNA chains is rapidly replicated, producing a large, readily analyzed sample of a piece of DNA; the process is (PCR PCR polymerase chain reaction.
polymerase chain reaction
Polymerase chain reaction (PCR) ) products of the 16S rRNA gene (3) from the organism represented a previously unknown mycobacterial species (EMBL EMBL European Molecular Biology Laboratory
EMBL Eniwetok Marine Biological Laboratory DNA DNA: see nucleic acid.
or deoxyribonucleic acid
One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes. 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 ileal /il·e·al/ (il´e-ahl) pertaining to the ileum.
Of or relating to the ileum.
pertaining to the ileum. 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 duodenal /du·o·de·nal/ (doo?o-de´n'l) (doo-od´ah-n'l) of or pertaining to the duodenum.
Refers to the duodenum, or the first part of the small intestine. 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 cachexia /ca·chex·ia/ (kah-kek´se-ah) a profound and marked state of constitutional disorder; general ill health and malnutrition. developed. Repeat endoscopy showed yellow, plaquelike lesions in the duodenum duodenum: see intestine; pancreas.
First and shortest (9–11 in., or 23–28 cm) segment of the small intestine. It curves down and then up from the pylorus of the stomach, where chyme enters it. (online Appendix Figure; available at http://www.cdc.gov/ncidod/EID/vol 1 2no03/05-1139-G1.htm) 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. AF 144747).
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 Nodules
A small mass of tissue in the form of a protuberance or a knot that is solid and can be detected by touch.
Mentioned in: Leprosy (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 Mycobacterium avium complex (MAC) is a group of genetically-related bacteria belonging to the genus Mycobacterium. It includes Mycobacterium avium subspecies avium (MAA), Mycobacterium avium subspecies hominis (MAH), and 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).
Dirk Wagner,* Margreet C. Vos, ([dagger])([[double dagger]]) Anton GM. Buiting, ([double dagger]) Annerose Serr, * Anneke M.C. Bergmans, ([section]) Winfried V. Kern, * and Leo M. Schouls ([paragraph])
* University Hospital, Freiburg, Germany; ([dagger]) Erasmus University Medical Center, Rotterdam, the Netherlands; ([double dagger]) St Elisabeth Hospital, Tilburg, the Netherlands; ([section]) Franciscus Hospital, Roosendaal, the Netherlands; and ([paragraph]) National Institute of Public Health and the Environment, Bilthoven, the Netherlands
(1.) Brown-Elliott BA, Griffith DE, Wallace RJ Jr. Newly described or emerging human species of nontuberculous mycobacteria. Infect Dis Clin North Am. 2002; 16:187-220.
(2.) Wagner D, Young LS. Nontuberculous mycobacterial infections. Infection. 2004;32:257-70.
(3.) Kirschner P, Springer B, Vogel U, Meier A, Wrede A, Kiekenbeck M, et al. Genotypic identification of mycobacteria by nucleic acid sequence determination: report of a 2-year experience in a clinical laboratory. J Clin Microbiol. 1993;31:2882-9.
(4.) Buiting A, Vos M, Bergmans A, Schouls L. A new mycobacterial species causing disseminated infection. 35th Interscience Conference on Antimicrobial Agents and Chemotherapy Antimicrobial Agents and Chemotherapy (print-ISSN 0066-4804, CODEN AMACCQ; canceled ISSN 0074-9923, canceled CODEN AACHAX) is an academic journal published by the American Society for Microbiology. . San Francisco 1995; Abstract K45. Washington: American Society for Microbiology The American Society for Microbiology (ASM) is a scientific organization, based in the United States although with over 43,000 members throughout the world. It is the largest single life science professional organization and its members include those whose interests encompass basic ; 1995.
(5.) Realini L, De RK, Hirschel B, Portaels F: Blood and charcoal added to acidified acidified /acid·i·fied/ (ah-sid´i-fid) having been made acid. agar media promote the growth of Mycobacterium genavense. Diagn Microbiol Infect Dis. 1999;34:45-50.
(6.) Selvarangan R, Wu WK, Nguyen TT, Carlson LD, Wallis CK, Stiglich SK, et al. Characterization of a novel group of mycobacteria and proposal of Mycobacterium sherrisii sp. nov. J Clin Microbiol. 2004;42:52-9.
(7.) Wayne LG, Good RC, Bottger EC, Butler R, Dorsch M, Ezaki T, et al. Semantide- and chemotaxonomy-based analyses of some problematic phenotypic clusters of slowly growing mycobacteria Mycobacteria that form colonies clearly visible to the naked eye in more than 7 days on subculture are termed slow growers. List of slowly growing Mycobacteria
(8.) Hughes MS, James G, Ball N, Scally This article or section may contain original research or unverified claims.
Please help Wikipedia by adding references. See the for details.
This article has been tagged since September 2007. M, Malik R, Wigney DI, et al. Identification by 16S rRNA gene analyses of a potential novel mycobacterial species as an etiological agent of canine leproid granuloma granuloma /gran·u·lo·ma/ (gran?u-lo´mah) pl. granulomas, granulo´mata an imprecise term for (1) any small nodular delimited aggregation of mononuclear inflammatory cells, or (2) such a collection of modified macrophages syndrome. J Clin Microbiol. 2000;38:953-9.
(9.) Richter E, Rusch-Gerdes S, Niemann S, Stoehr A, Plettenberg A. Detection, identification, and treatment of a novel, non-cultivable Mycobacterium species in an HIV HIV (Human Immunodeficiency Virus), either of two closely related retroviruses that invade T-helper lymphocytes and are responsible for AIDS. There are two types of HIV: HIV-1 and HIV-2. HIV-1 is responsible for the vast majority of AIDS in the United States. patient. AIDS. 2000; 14:1667-8.
(10.) Kolditz M, Halank M, Spornrafl-Ragaller P, Schmidt H, Hoffken G: Localized pulmonary infection associated with Mycobacterium tilburgii in an HIV-infected patient. Infection. 2005;33:278-81.
Address for correspondence: Dirk Wagner, Center for Infectious Diseases and Travel Medicine, University Hospital, Hugstetter Str 55, D-79106 Freiburg, Germany; fax: 49-761-270-1820; email: firstname.lastname@example.org
Table. Characteristics of patients with confirmed "Mycobacterium tilburgii" disease * Immuno- CD4 count Sex (age, y) suppression (cell/[micro]L) Disease manifestation F (45) No Normal Bladder, intestinal lymphnodes, stomach, ileum, colon M (34) AIDS 37 Esophagus, duodenum M (35) AIDS 20 Duodenum, abdominal lymph nodes M (41) AIDS 17 Pulmonary nodules Sex (age, y) Treatment (duration, mo) Diagnosed in F (45) Pyrazinamide, isoniazid, rifampin (5); The ethambutol, ciprofloxacin, Netherlands clarithromycin, rifampin (11); surgical resection M (34) Ethambutol, clarithromycin, Germany rifabutin (5) M (35) Ethambutol, clarithromycin, Germany rifabutin (12 ([dagger])) M (41) Surgical resection; Germany ethambutol, ciprofloxacin, clarithromycin (6); ethambutol, clarithromycin (12 ([double dagger])) Sex (age, y) Reference F (45) This study M (34) This study M (35) (9) M (41) (10) * F, female, M, male. ([dagger]) 6 weeks ineffective. ([double dagger]) Ongoing.