To the Editor: Streptococcus equi belongs to the pyogenic group of streptococci and
to group C of the Lancefield classification. It consists of 3 subspecies of zoonotic
agents rarely reported as human pathogens (
1
,
2
): S. equi subsp. equi, S. equi subsp. zooepidemicus, and S. equi subsp. ruminatorum.
We report here a case of human infection caused by S. equi subsp. ruminatorum. (
3
).
A 53-year-old man was admitted to an intensive care unit of our hospital (University
Teaching Hospital, Montpellier, France) on April 28, 2006, with a high fever and in
a comatose state. The day before, he had experienced headache and neck pain. He had
been infected with HIV for 9 years but had not had an opportunistic infection. His
ongoing HIV treatment consisted of ritonavir, lopinavir, abacavir, lamivudine, and
co-trimoxazole; 3 weeks before admission, his blood CD4+ T-cell count was 133/μL,
and viral load was 118,000 copies/mL. At the time of admission, his body temperature
was 38.9°C, heart rate was 105 beats/min, and blood pressure was 55/35 mmHg. He exhibited
a fixed pupil in 1 eye, neck stiffness, and was nonresponsive. He had bilateral pulmonary
infiltrates and severe hypoxemia. Treatment consisted of mechanical ventilation, fluid
therapy, and norepinephrine. Laboratory investigations found the following: leukocyte
count 9,600/mm3 with 90% neutrophils, hemoglobin level 9.0 g/dL, platelet count 32,000/mm3,
C-reactive protein value 159 mg/L, and blood lactate concentration 3.2 mmol/L. Computed
tomographic scanning of the brain showed no hemorrhage or edema. Lumbar puncture produced
turbid cerebrospinal fluid (CSF) with 300 leukocytes/mm3 (95% neutrophils), protein
5.6 g/L, glucose <0.1 mmol/L, and gram-positive cocci. Three sets of aerobic-anaerobic
blood cultures and bronchial aspirates were sampled, and intravenous treatment with
dexamethasone (10 mg/6 h/day), cefotaxime (2 g/4 h/day), and vancomycin (30 mg/kg/day)
was initiated. On day 2, the hemodynamic state was stabilized, but brain death occurred.
All sets of aero-anaerobic blood cultures, CSF, and bronchial aspirate fluid yielded
the growth of a catalase-negative, β-hemolytic, gram-positive cocci belonging to the
Lancefield group C of streptococci. Antimicrobial susceptibility testing showed a
bacterium fully susceptible to antibiotics tested. MICs of penicillin, amoxicillin,
and cefotaxime were 0.047, 0.125, and 0.125 mg/L, respectively. The isolates were
identified as S. equi by using the Vitek2 system, rapid ID32 STREP, and API 20 STREP
strips (bioMérieux, Marcy l’Etoile, France), but phenotype was inconclusive for subspecies
identification. The strains were identified as S. equi subsp. zooepidemicus by Vitek2,
but aesculin was not hydrolyzed, and D-ribose fermentation was noted, as previously
described for S. equi subsp. ruminatorum. 16S rRNA gene–based identification was performed
as previously described (
4
) on strain ADV 6048.06 from blood. The 1,396-bp sequence (GenBank accession no. EF362949)
was compared with databases by using the BLAST program (
5
); the sequence differed by only 1 nucleotide position (>99.9% identity) from the
sequence of S. equi subsp. ruminatorum CECT 5772T. Other primarily related sequences
were from S. equi subsp. ruminatorum strains of animal origin (99.5%–99.9% identity)
and from S. equi subsp. zooepidemicus, (98.7% identity). Phylogenetic trees clustered
the clinical isolate with S. equi subsp. ruminatorum strains to form a robust lineage,
well separated from other strains of S. equi and supported by a high bootstrap value
(Figure).
Figure
Neighbor-joining tree showing the phylogenetic placement of strain ADV 6048.06 (boldface)
among members of the Streptococcus equi species in the pyogenic group of streptococci.
Twenty-three 16S rRNA gene sequences selected from the GenBank database were aligned
with that of strain ADV 6048.06 by using ClustalX 1.83 (available from http://bips.u-strasbg.fr/fr/documentation/ClustalX).
Alignment of 1,263 bp was used to reconstruct phylogenies by using PHYLIP v3.66 package
(http://evolution.genetics.washington.edu/phylip.html). The neighbor-joining tree
was constructed with a distance matrix calculated with F84 model. Numbers given at
the nodes are bootstrap values estimated with 100 replicates. S. pneumoniae is used
as outgroup organism. Accession numbers are indicated in brackets. The scale bar indicates
0.005 substitutions per nucleotide position. Maximum likelihood and parsimony trees
were globally congruent with the distance tree and confirmed the placement of the
strain ADV 6048.06 in the S. equi subspecies ruminatorum (SER) lineage. SEZ, S. equi
subspecies zooepidemicus.
S. equi subsp. equi and S. equi subsp. zooepidemicus are zoonotic agents implicated
in diverse animal infections such as strangles, mastitis, abscesses, wounds, and respiratory
and uterine infections. Human infections caused by S. equi subsp. equi, and S. equi
subsp. zooepidemicus included outbreaks of foodborne diseases (
6
,
7
), meningitis, septicemia, arthritis, pneumonia, glomerulonephritis, and streptococcal
toxic shock syndrome, in both immunocompromised and immunocompetent patients (
1
,
2
,
8
,
9
). S. equi subsp. ruminatorum was described in 2004 in domestic sheep and goats with
mastitis (
3
). More recently, it was isolated during severe infections in spotted hyenas and zebras
(
10
). No human isolate has been reported to date. Moreover, none of the 3 subspecies
of S. equi has been isolated from HIV-infected patients. The current case underlines
the conclusion that molecular identification of S. equi subsp. ruminatorum is essential.
S. equi subsp. ruminatorum could have been underestimated due to its potential misidentification
as S. equi subsp. zooepidemicus by phenotypic tools. Despite the rare occurrence of
group C streptococci in human infections, a high death rate is reported for invasive
infections (
7
–
9
). S. equi subsp. zooepidemicus produce superantigen exotoxin that may have been implicated
in the pathogenesis of fatal infection (
2
); S. equi subsp. ruminatorum should also be investigated for potential virulence
factors for humans.
Epidemiologic investigations were unsuccessful in tracing the patient’s infection
to an animal source. The respiratory tract, from which S. equi subsp. ruminatorum
was recovered in pure culture, could be considered the most probable portal of entry.
The mode of S. equi subsp. ruminatorum transmission to humans remains unknown. More
information is needed on its reservoirs, but they likely resemble those of S. equi
subsp. equi, and S. equi subsp. zooepidemicus (
2
,
6
,
7
). Prevention of human infections due to S. equi should include frequent microbiologic
sampling of lactating animals and control measures for unpasteurized dairy products
(
7
). Better characterization of underlying conditions that increase risk of invasive
S. equi infections is also needed. This knowledge could help define high-risk groups
of persons and could lead to generation of specific preventive recommendations.