To the Editor: The genus Mycobacterium contains various obligate and opportunistic
pathogens of animals, which may also be transmitted to humans and cause disease in,
thus exhibiting a considerable zoonotic potential (
1
,
2
). During the past few decades, members of the Mycobacterium avium-intracellulare
complex (MAIC) emerged as pathogens of human diseases, including lymphadenitis in
children, pulmonary tuberculosis-like disease, and disseminated infections (occurring
predominantly in immunocompromised persons, particularly AIDS patients) (
1
,
2
). Similarly, important animal diseases are caused by members of this group, e.g.,
avian tuberculosis and paratuberculosis in ruminants (
1
). MAIC includes M. intracellulare and 4 subspecies of M. avium, namely, M. avium
subsp. avium, M. avium subsp. hominissuis, M. avium subsp. silvaticum, and M. avium
subsp. paratuberculosis (
3
,
4
). Whereas members of the M. tuberculosis complex are transmitted by direct host contact,
MAIC species are acquired predominantly from environmental sources, including soil,
water, dust, and feed. Subclinical infections are common among birds (
1
,
2
).
M. avium strains differ from M. intracellulare by containing the insertion sequence
(IS) IS1245 (
3
) and are further discriminated by terms of IS901 (
4
). Avian isolates (M. avium subsp. avium) are usually positive for IS901 and represent
the main pathogen of avian tuberculosis (
5
). In contrast, mammalian isolates are IS901-negative and have been designated as
M. avium subsp. hominissuis because of their predominant hosts. This subspecies is
only weakly virulent for birds but causes disease in animals and humans (
5
).
Even though M. tuberculosis and M. bovis are the common etiologic agents of canine
mycobacteriosis, dogs are reported to be relatively resistant to M. avium infection
(
6
,
7
). Nonetheless, sporadic cases usually show nonspecific clinical signs, whereas necropsy
consistently reveals granulomatous inflammation in numerous organs, including lymph
nodes, intestine, spleen, liver, lung, bone marrow, and even spinal cord (
7
,
8
). The predominant involvement of the gastrointestinal tract indicates an oral route
of infection (
7
,
8
), and simultaneously increases the risk for human infection by fecal spread of mycobacteria.
Our report concerns 2 young dogs, a 3-year-old miniature schnauzer and a 1-year-old
Yorkshire terrier, that lived in different geographic regions in Germany. Both had
had therapy-resistant fever, lethargy, progressive weight loss, and generalized lymphadenomegaly
for several weeks and were euthanized after a final phase of diarrhea. Necropsy findings,
similar in both dogs, included generalized enlargement of lymph nodes with a whitish,
granular to greasy cut surface, leading to intraabdominal adhesions by extensive involvement
of mesenteric lymph nodes. In the terrier, the greater omentum and a part of the right
apical lung lobe showed changes similar to those in the lymph nodes. Furthermore,
numerous white 1-mm nodules were found in the spleen (both dogs), liver (schnauzer)
and costal pleura (terrier).
Histologic examination showed (pyo-)granulomatous inflammation of lymph nodes, tonsils,
liver, spleen, and greater omentum. Additionally, pyogranulomatous pleuropneumonia
was present in the terrier, and a granulomatous enteritis and pyelitis in the schnauzer.
The granulomatous lesions frequently exhibited central necrosis surrounded by macrophages,
epitheloid cells, and few neutrophils (Figure, panel A). However, multinucleated giant
cells or mineralization was not observed. In both animals, Ziehl-Neelsen stain demonstrated
large numbers of acid-fast bacilli within macrophages (Figure, panel B). Samples of
lymph nodes and lung were processed for mycobacterial culture by using standard procedures
(Löwenstein-Jensen, Stonebrink medium). Colonies emerging after 2-week incubation
at 37°C were investigated by PCR targeting IS1245 and IS901 (
3
,
4
). In all samples, M. avium subsp. hominissuis was identified by growth characteristics
as well as presence of an IS1245-specific and absence of an IS901-specific PCR product.
Additionally, sequencing of hsp65 was conducted (
9
), which indicated M. avium subsp. hominissuis in both dogs (GenBank accession nos.
EU488724 and EU488725).
Figure
A) Mesenteric lymph node of Yorkshire Terrier shows diffuse granulomatous lymphadenitis
with extensive infiltration of macrophages, foci of pyogranulomatous inflammation
(arrowhead), and focal necrosis (asterisk). Hematoxylin and eosin stain; scale bar
represents 100 μm. B) Retropharyngeal lymph node of schnauzer shows innumerable acid-fast
bacilli (arrows) within the cytoplasm of macrophages. Ziehl-Neelsen stain; scale bar
represents 25 μm.
Despite improved therapeutic approaches, MAIC infection represents a frequent bacterial
complication in persons with AIDS. However, several studies showed a very low incidence
of M. avium subsp. avium infections in humans. Thus, most of these HIV-related infections
are attributed to M. avium subsp. hominissuis (
2
,
5
). Unfortunately, the subspecies of M. avium was not identified in most canine cases
reported in the literature (
7
,
8
). Nonetheless, different serotypes of M. avium, corresponding to either M. avium
subsp. avium or M. avium subsp. hominissuis, have been identified sporadically (
6
,
10
). The source and route of infection were unclear in all reports including ours, albeit
repeatedly observed enteritis strongly suggested an oral mode of infection. A common
environmental or wildlife reservoir represents the most probable source of M. avium
infection for both humans and animals. However, there is also evidence of direct transmission
(
1
–
3
). Therefore, M. avium subsp. hominissuis infection in dogs may comprise a considerable
zoonotic potential, particularly if pet dogs with close contact to the owner are affected
and if prolonged nonspecific clinical signs and intestinal involvement occur, as demonstrated
here.