Download Severe Pulmonary Involvement in a Case

BRIEF REPORT
Severe Pulmonary Involvement in
a Case Attributed to Domestically
Acquired Seoul Hantavirus in the
United States
Ingrid L. Roig,1 Daniel M. Musher,1,2 and David J. Tweardy1
1Section of Infectious Diseases, Department of Medicine, Baylor College of
Medicine, and 2Michael E. DeBakey Veterans Affairs Medical Center, Houston,
Texas
Hantavirus is known to cause 2 distinct clinical syndromes:
hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome. Seoul virus is an Old World
hantavirus known to cause HFRS. We report a case attributed to domestically acquired Seoul hantavirus with prominent pulmonary involvement and a fatal outcome.
The majority of known hantaviruses are naturally hosted by
rodents (order Rodentia, superfamily Cricetidae and Muridae) as well as moles (order Talpidae) and shrews (order
Soricidae) [1].
Hantavirus causes 2 known diseases in humans: hemorrhagic
fever with renal syndrome (HFRS) and hantavirus pulmonary
syndrome (HPS). Both syndromes share many clinical features,
leading many investigators to consider them to be different
manifestations of a similar pathogenic process. Seoul hantavirus
is an Old World hantavirus that has been linked to a milder form
of HFRS in Asia and Europe. Only 1 human case of domestically
acquired infection has been described in the United States [2],
although seroprevalence studies in the last decade have detected
antibodies to Hantaan and Seoul viruses in domestic rats [3, 4].
Here we report a case of severe pulmonary involvement with
positive serology suggestive of domestically acquired Seoul virus
infection.
Received 7 May 2011; accepted 13 September 2011; electronically published 31 October
2011.
Correspondence: Ingrid L. Roig, MD, Section of Infectious Diseases, Department of
Medicine, Baylor College of Medicine, One Baylor Plaza, BCM 286, N1319, Houston, Texas
77030 ([email protected]).
Clinical Infectious Diseases 2012;54(1):91–4
Ó The Author 2011. Published by Oxford University Press on behalf of the Infectious
Diseases Society of America. All rights reserved. For Permissions, please e-mail:
[email protected].
DOI: 10.1093/cid/cir748
Case Report
In April 2010, a 33-year-old obese hispanic male resident of
Brazoria County, Texas, was hospitalized with a 7-day history of
upper respiratory symptoms, nonproductive cough, pleuritic
chest pain, and shortness of breath. He was in severe respiratory
distress (oxygen saturation 50%) and required immediate intubation. His past medical history was unremarkable. He worked
as a sandblaster and had not traveled outside Brazoria County. He
denied direct exposure to rodents.
His temperature was 102°F; he was hypotensive on vasopressors with a pulse rate of 120 and a respiratory rate of 36. On
an oscillator machine with a fraction of inspired oxygen of 100%,
his oxygen saturation was 80%. He had prominent flushing of the
face, neck, and chest and coarse breath sounds, but no rashes,
petechiae, peripheral edema, or ascites. Laboratory evaluation on
the day of admission showed hemoconcentration, mild thrombocytopenia, hyponatremia, hypoalbuminemia, mild proteinuria,
and elevations in liver enzymes, creatinine, lactic dehydrogenase,
and lactic acid (Table 1). A chest radiograph showed diffused
bilateral patchy opacities.
His initial electrocardiogram (EKG) showed right-axis deviation
with normal sinus rhythm and an isolated T-wave inversion in an
inferior lead. Echocardiography showed mildly depressed left
ventricular function with a normal left ventricular size and a dilated right ventricle with severe pulmonary hypertension.
The patient was treated empirically with vancomycin, cefepime,
azithromycin, and oseltamivir. Bacterial cultures of urine and
blood were negative. Routine cultures of bronchoscopic washings
were negative for bacterial pathogens. Tests for human immunodeficiency virus, Legionella, Histoplasma, and Streptococcus
pneumoniae were negative. Both nasal swab for influenza A and B
and H1N1 PCR were negative. Bronchoalveolar lavage fluid
showed plasmacytoid and plasmablastic cells consistent with
immunoblasts (Figure 1). Despite maximal oxygenation, the patient’s respiratory status worsened, his renal function deteriorated,
he developed cardiac arrest, and he died 6 days after admission.
Comment
The sudden onset of a febrile illness with severe respiratory
compromise and capillary leak syndrome in the absence of any
other positive findings raised consideration of hantaviral infection. A serum sample was sent to the Special Pathogens Branch,
Centers for Disease Control and Prevention, for hantavirus serologic testing. The test revealed immunoglobulin (Ig) M to Seoul
hantavirus at 1:1600 dilution; IgG was undetectable, as were IgM
and IgG for Sin Nombre virus. Enzyme-linked immunosorbent
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Table 1. Laboratory Findings of a 33-Year-Old Hispanic Man a Week After Onset of Symptoms of Seoul Virus Infection
Specimen
On admission
3
Day 3 of hospitalization
Day 6 of hospitalization
Reference range
9100
14 900
21 700
90
90
89
50–70
Lymphocytes, %
5
6
1
20–40
Hemoglobin, g/dL
18.8
17.9
17
14–18
Hematocrit, %
62.1
62.7
60.3
White blood cell count, cells/mm
Neutrophils, %
No. of platelets/mm3
Sodium, mg/dL
114
130
156
139
202
142
Urea nitrogen, mg/dL
42
70
56
Creatinine, mg/dL
1.7
Albumin, g/dL
1.4
4.1
40–54
150–400
136–145
7–18
0.6–1.3
N/A
3.4–5.0
Alanine aminotransferease, IU/L
29
38
N/A
30–65
Aspartate aminotransferase, IU/L
106
152
N/A
Lactic acid, mmol/L
Fibrinogen, mg/dL
Lactate dehydrogenase, IU/L
Brain natriuretic peptide, pg/mL
pH
1.2
6.0
4500–12 000
4.3
N/A
544.7
1206
N/A
N/A
N/A
N/A
10
N/A
N/A
7.41
7.21
1.9
7.21
15–37
0.4–2.0
180–480
100–190
0–100
7.35–7.45
pCO2, mm Hg
56
75
71
pO2, mm Hg
38
57
40
32–45
72–104
HCO3, mmol/L
35
28.6
28
22–26
11
12
12
12
Urine
Protein (dipstick)
Blood (dipstick)
N/A
N/A
Negative
Negative
Abbreviation: N/A, not available.
assay was strongly positive for IgM (optical density [OD], 3.28)
and negative for IgG (OD, 0.24) to Seoul virus antigens.
Autopsy showed cardiomegaly, hepatomegaly, nephromegaly, and splenomegaly with the presence of a splenic
infarct; pleural, pericardial, and peritoneal effusions were
noted. There were no signs of hemorrhage within the endocardium or myocardium. Microscopic review of the lung
tissue showed diffuse changes suggestive of nonspecific or
viral pneumonia with intra-alveolar hemorrhage and focal
thrombus formation. The liver showed severe autolysis
without inflammation. The renal cortex showed large glomeruli. No signs of inflammation or tubular necrosis were
identified. Immunohistochemical identification of hantavirus
in kidney and lung tissue was unsuccessful.
An environmental assessment of the patient’s home showed
evidence of rodent infestation (urine, feces). Unfortunately, no
rodents were trapped and tested for Seoul infection. There were
no reports of a similar illness among family members.
Discussion
Figure 1. Immunoblasts (white arrows) seen on bronchoalveolar
lavage. Magnification 3400.
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We believe this case is suggestive of domestically acquired
Seoul hantavirus infection in the United States, showing an
overlap between HPS and HFRS. Although hantaviral immunohistochemistry studies on tissues obtained at autopsy
were negative, his clinical presentation, high anti-Seoul hantavirus IgM titer with a negative IgG titer, failure to detect
another etiological agent, and presence of the rodent reservoir
throughout Texas suggest that this case was likely caused by
Seoul virus.
Although there was no known prior medical disease reported in
our patient, the finding of severe pulmonary hypertension on
echocardiography and right-sided axis on the initial EKG may be
attributable to his obese condition, causing previously undiagnosed obstructive sleep apnea and/or obesity hypoventilation
syndrome, or to occupational lung disease. However, neither
alone nor together would these findings explain why the patient
had noncardiogenic pulmonary edema upon presentation.
Our patient showed features compatible with both syndromes
caused by hantavirus. His initial presentation with respiratory
failure and noncardiogenic pulmonary edema, as documented
by his low B-type natriuretic peptide blood test, was more
consistent with HPS. His subsequent development of flushing of
the skin, conjunctival injection, renal involvement, and intraalveolar hemorrhage was characteristic of HFRS.
The prior understanding that Old World hantaviruses cause
HFRS and are limited to the European and Asian continents has
been revised in the past decade or so. Growing evidence, including this case, suggests that the syndrome caused by these
strains is no longer limited to 1 syndrome or another; rather,
patients infected by these strains present with varying degrees of
overlap between the 2 syndromes.
Seoul virus is a known Old World hantavirus that occurs
across Asia and Europe [1]. Although mainly an urban disease
due to the host distribution, cases have been identified among
farmers and workers, as well as laboratory workers, in diseaseendemic areas. All cases of HFRS reported previously have
presented with a mild to moderate form of the disease.
Since 1993, 37 cases of Hantavirus have been reported in
Texas [5], 6 due to Bayou strain, 29 to Sin Nombre, and, in 2
cases, to an unknown strain. This is the first reported case to
occur due to Seoul virus.
Rattus norvegicus and Rattus rattus are the primary rodent
reservoirs of Seoul virus. These species of rats are distributed
worldwide, including the United States. In the last decade, studies
in limited US urban areas have shown a seroprevalence of
50%–58% [3] of Seoul virus antibodies in rats and 0.5%–1.6%
[6] in humans. No previous epizootiologic and epidemiologic
studies have been conducted previously in Brazoria County, although Seoul virus has been isolated from Norway rats in
a neighboring county [7].
Seoul virus may cause a less severe form of HFRS clinically
distinct from HPS, with a mortality rate of 1%–2% [1]. Although
pulmonary symptoms have occasionally been described with
other viruses causing HFRS [8–10], there has not been a case of
Seoul virus showing a clear overlap between both syndromes.
HFRS and HPS share some clinical and laboratory features.
The earliest clinical manifestations described are headache,
chills, myalgia, malaise, and a fever of rapid onset [1, 8, 11]. This
is usually followed by nausea, vomiting, and abdominal pain.
Respiratory symptoms, such as cough, sore throat, and dyspnea,
are less commonly seen in HFRS [8] but are the primary
symptoms reported in HPS [11, 12]. Microvascular instability
with vascular leakage is the pathologic hallmark of both syndromes, with vascular changes occurring in the lungs in HPS
and in the kidneys in HFRS. HPS is characterized by rapid development of respiratory failure and cardiogenic shock, with
a mortality rate of about 35%–40% [1, 11, 12]. HFRS usually
presents with various degrees of renal involvement, occasionally
with frank hemorrhage, and has a mortality rate ranging from
,1% to 12%, depending on the causative virus. Pulmonary
edema is not a frequent complication of HFRS [10]; when
present, it usually occurs during the final stages of the disease
(oliguric and diuretic phase).
Laboratory findings common to both syndromes are leukocytosis with left shift, low albumin, thrombocytopenia, high
hematocrit due to capillary leak, azotemia, transaminitis, and
presence of immunoblasts (activated lymphocytes with plasmacytoid features) that can be seen in lungs, blood, bone marrow,
liver, or spleen.
There are no specific therapies available to treat diseases caused
by hantavirus, with the exception of intravenous ribavirin, which
has shown some benefit in the treatment of Hantaan virus infections [1]. Supportive care remains the cornerstone of management and includes early use of vasopressors, mechanical
ventilation, and cautious use of intravenous fluid.
Notes
Acknowledgment. We thank Dr Adam Macneil from the Special
Pathogens Branch at the Centers for Disease Control and Prevention for
information on prior Seoul virus cases in the United States as well as for
details on the serologic testing done to our patient.
Potential conflicts of interest. All authors: No reported conflicts.
All authors have submitted the ICMJE Form for Disclosure of Potential
Conflicts of Interest. Conflicts that the editors consider relevant to the
content of the manuscript have been disclosed.
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