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Letter
Mycobacterium neoaurum
Contamination
To the Editor: In reviewing "Rapidly Progressive Dementia
due to Mycobacterium neoaurum Meningoencephalitis," by Heckman
et al. (1), I found, contrary to the authors' conclusion,
that M. neoaurum was more likely a contaminant than a cause. First,
within the granulomatous brain lesions, the strongest evidence for the
authors' conclusion, no acid-fast bacilli were isolated or identified
on special stains; thus, the Kochs postulates were not satisfied. Rather,
the lesions were likely rheumatoid nodules. Longstanding rheumatoid arthritis
commonly causes granulomalike rheumatoid nodules. I did a PubMed search
using "rheumatoid nodule in the brain" and 7 articles were found
(2,3). A "rheumatoid endarteritis" search
found 25 articles. Heckman et al. failed to exclude or discuss this possibility.
Second, M. neoaurum is a rare environmental mycobacterium that
grows in ≤2 days on sheep blood agar and is not difficult to culture.
As the authors stated, there have been 8 reports of this organism, 7 isolated
from blood and 1 from urine. The blood isolates were associated with either
central venous catheter or intravenous drug use. Thus, M. neoaurum
is of low virulence and unlikely to cause spontaneous infection in tissue
unless inoculated accidentally, perhaps. Third, polymerase chain reaction
(PCR) is exquisitely sensitive and prone to contamination. The problem
is worse when bacterial DNA is amplified by using highly conserved primers.
The PCR reagents, from the Taq polymerase (of bacterial origin) to water,
contain sufficient, despite minute quantity, bacterial DNA to be amplified
(4). Although direct sequencing of the amplicon is often
blurry because of its low quantity and mixed content, when cloned, each
amplicon may be ligated to the vector and proliferates and gets sequenced
later.
Therefore, I believe the presence of M. neoaurum DNA, not the
organism itself, represented contamination. Generally, drawing cause-disease
conclusion based on PCR sequencing needs vigilance to satisfy the modified
Koch postulates (5).
Xiang Y. Han*
*University of Texas, Houston, Texas, USA
Suggested citation
for this article:
Han XY. Mycobacterium neoaurum contamination [letter]. Emerg Infect
Dis [serial on the Internet]. 2005 Aug [date cited]. Available
from http://www.cdc.gov/ncidod/EID/vol11no08/04-0861-05-0630.htm
References
- Heckman GA, Hawkins C, Morris A, Burrows LL, Bergeron
C. Rapidly
progressive dementia due to Mycobacterium neoaurum meningoencephalitis.
Emerg Infect Dis. 2004;10:924–7.
- Karam NE, Roger L, Hankins LL, Reveille JD. Rheumatoid
nodulosis of the meninges. J Rheumatol. 1994;21:1960–3.
- Kim RC, Collins GH. The
neuropathology of rheumatoid disease. Hum Pathol. 1981;12:5–15.
- Han XY, Pham AS, Tarrand JJ, Sood PK, Luthra R. Rapid
and accurate identification of mycobacteria by sequencing hypervariable
regions of the 16S ribosomal RNA gene. Am J Clin Pathol. 2002;118:796–801.
- Fredericks DN, Relman DA. Sequence-based
identification of microbial pathogens: a reconsideration of Koch's postulates.
Clin Microbiol Rev. 1996;9:18–33.
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In Response: In response to our report on a
case of rapidly progressive dementia (1,2), Dr. Han
argues that Mycobacterium neoaurum was "more likely a contaminant
than the cause" and that the actual cause of death was most likely
rheumatoid pachymeningitis. Dr. Han bases his argument on the absence
of positive acid-fast stains or mycobacterial cultures and his assessments
that the identification of M. neoaurum DNA was due to contamination
and that the pathologic findings represented rheumatoid nodules.
The inability to stain or culture an organism in this case is not unusual,
as paucibacillary mycobacterial infections, such as tuberculous lymphadenitis
and leprosy, are common (3,4). Though the possibility
is not inconceivable, environmental contamination is unlikely, because
tissue samples were positive with M. neoaurum–specific primers,
whereas controls containing identical reagents but no tissue were not.
Dr. Han expresses a valid concern that rheumatoid pachymeningitis was
not given due consideration. Rheumatoid pachymeningitis is a rare complication
of rheumatoid arthritis, in which patients may exhibit headache, cranial
neuropathies, focal deficits, seizures, or cognitive dysfunction (5,6).
Rheumatoid pachymeningitis usually, but not exclusively, occurs in patients
with long-standing rheumatoid arthritis characterized by erosive disease
and extra-articular manifestations, although the systemic disease may
be quiescent when neurologic complications arise. Cerebrospinal fluid
analysis is generally nonspecific. Magnetic resonance imaging may show
prominent meningeal enhancement. Pathologic features may include vasculitis,
rheumatoid nodules, and meningeal inflammation, with the latter 2 features
being most common (5). The dura may demonstrate inflammation
with fibrinoid necrosis (6). We reviewed the pathologic
specimens of this case and confirmed the presence of abundant giant cells,
endarteritis proliferans, and, most notably, extensive caseation necrosis
typical of mycobacterial infection. We found no evidence of rheumatoid
nodules, dural inflammation, or fibrinoid necrosis.
Though this case does not satisfy Kochs postulates, neither do most novel
infectious diseases. Substantial international efforts were required to
satisfy the postulates in the case of SARS (7). In this
case, the identification of DNA from a "rare environmental mycobacterium"
in a patient with overwhelming pathologic evidence of mycobacterial infection
provides strong, though not foolproof, evidence of a possible causal role.
George A. Heckman,*
Cynthia Hawkins,† Andrew Morris,‡ Lori L. Burrows,† and Catherine Bergeron§
*Chedoke Campus and Freeport Health Centre, Kitchener, Ontario, Canada;
†University of Toronto, Toronto, Ontario, Canada; ‡McMaster University,
Hamilton, Ontario, Canada; §Toronto Western Hospital, Toronto, Ontario,
Canada
Suggested citation
for this article:
Heckman GA, Hawkins C, Morris A, Burrows LL, Bergeron C. Mycobacterium
necaurum contamination [in response]. Emerg Infect Dis [serial on
the Internet]. 2005 Aug [date cited]. Available from http://www.cdc.gov/ncidod/EID/vol11no08/04-0861_05-0630.htm
References
- Han XY. Mycobacterium neoaurum contamination.
Emerg Infect Dis. 2005;11:1316–7.
- Heckman GA, Hawkins C, Morris A, Burrows LL, Bergeron C. Rapidly
progressive dementia due to Mycobacterium neoaurum meningoencephalitis.
Emerg Infect Dis. 2004;10:924–7.
- Chao SS, Loh KS, Tan KK, Chong SM. Tuberculous
and nontuberculous cervical lymphadenitis: a clinical review. Otolaryngol
Head Neck Surg. 2002;126:176–9.
- Ustianowski AP, Lockwood DNJ. Leprosy:
current diagnostic and treatment approaches. Cur Opin Infect Dis.
2003;16:421–7.
- Kato T, Hoshi K, Sekijima Y, Matsuda M, Hashimoto T, Otani M, et al.
Rheumatoid
meningitis: an autopsy report and review of the literature. Clin
Rheumatol. 2003;22:475–80.
- Tan HJ, Raymond AA, Phadke PP, Rozman Z. Rheumatoid
pachymeningitis. Singapore Med J. 2004;45:337–9.
- Osterhaus ADME, Fouchier RAM, Kuiken T. The
aetiology of SARS: Koch's postulates fulfilled. Philos Trans R Soc
Lond B Biol Sci. 2004;359:1081–2.
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