Hantavirus pulmonary syndrome (HPS) is a rare cardiopulmonary disease
caused by viruses of the genus Hantavirus, for which
rodents are the natural reservoir.1,2 Transmission
to humans occurs by direct contact with rodents or their excreta or by inhalation
of aerosolized infectious material (e.g., dust created by disturbing rodent
nests). In July 2004, HPS cases (including one fatal case) were reported in
two persons believed to have been exposed at sites approximately 12 miles
apart in Randolph County, West Virginia (2000 population: 28,254).3 This report describes the two cases and summarizes
their epidemiologic and environmental investigations. Clinicians and the public
need to be educated about the risk for HPS and methods to reduce that risk.
Patient A. In early July, a wildlife sciences
graduate student, a man aged 32 years, visited an emergency department (ED)
in Blacksburg, Virginia, with complaints of fever, cough, and sore chest since
the previous evening. The ED clinician noted possible rodent exposure in the
medical history of the patient. Examination revealed a temperature of 102.7°F
(39.3°C) and an oxygen saturation of 96% (normal). A complete blood count
(CBC) revealed a left shift with no bands (granulocytes: 87%) and lymphopenia
(lymphocytes: 400/mm3). Radiographic examination indicated faint
right-sided pneumonia. In the ED, the graduate student began vomiting and
was admitted for intravenous hydration and parenteral antibiotics. He became
progressively hypoxic, requiring supplemental oxygen, bilevel positive airway
pressure, and eventually intubation with mechanical ventilation. Repeated
radiographs revealed bilateral pulmonary edema.
The next day, the patient was hypotensive, requiring intravenous pressor
support. He received activated protein C to prevent disseminated intravascular
coagulation (DIC). A repeat CBC revealed bands (granulocytes: 20%) and a decreased
platelet count (115,000/mm3); urinalysis indicated mild hematuria
and proteinuria. Despite aggressive supportive care, the patient’s status
continued to deteriorate, and he died on the third day of his hospitalization.
Differential diagnosis included tularemia, pneumococcal sepsis, and HPS. Serum
specimens submitted to ARUP Laboratories (Salt Lake City, Utah) were positive
for both IgG and IgM antibodies to hantaviruses; these test results were confirmed
by CDC. A spleen biopsy was also positive by immunohistochemistry for hantavirus
antigens. A serum sample was positive for hantavirus RNA by real-time reverse
transcriptase-polymerase chain reaction (RT-PCR). Sequencing of the amplified
nucleic acid identified the virus as Monongahela hantavirus.4
According to interviews with his coworkers, the patient had spent the
previous month trapping small mammals for study and handling mice (Peromyscus spp.) daily. Two students and a recent graduate who had
worked with the patient reported that none of them had consistently worn gloves
while handling rodents or washed their hands after handling rodents or their
excreta, even before eating. The students also reported frequent rodent bites
on their bare hands.
Patient B. In early July, a Randolph County
resident, a man aged 41 years, spent a weekend at a log cabin with his family.
Two days later, he had fatigue, a dull headache, and a mild fever. The following
day, he had a temperature of 102.9°F (39.4°C). The next morning, he
visited his primary-care physician with hematuria but no fever and was released
on empiric antibiotic therapy for a possible urinary tract infection.
The patient returned 2 days later with a severe headache of approximately
12 hours’ duration; he was referred immediately to the local ED. On
arrival, the patient was hypoxic with a room air oxygen saturation of 90%;
chest radiographs revealed right-sided pneumonia and congestive heart failure.
The patient was airlifted to a referral hospital, with hypotension and bradycardia.
His white blood cell count was normal, and cardiac enzymes were negative.
The patient was placed in the intensive care unit and administered intravenous
pressors and broad-spectrum antibiotics. Differential diagnosis included viral
myocarditis, atypical pneumonia, and opportunistic infection, and was later
broadened to include HPS and other infectious and autoimmune etiologies.
The patient was intubated the next day and started on high-frequency
oscillator ventilatory support. The patient’s condition deteriorated,
with onset of thrombocytopenia, DIC, hypoalbuminemia, and renal insufficiency
requiring hemodialysis. After 5 days of hospitalization, his condition began
to improve. Serum samples were reported positive for IgG and IgM antibodies
to hantaviruses by ARUP Laboratories; these results were confirmed by CDC.
In addition, a serum sample taken during his hospitalization was positive
for hantavirus RNA by RT-PCR. Sequencing of the amplified nucleic acid also
identified the virus as Monongahela hantavirus. The patient recovered slowly
during the next month.
According to family members, when the patient and his family arrived
at the cabin in early July, they aired the interior after finding it reeking
of rodent urine and discovered two live mice in a trash can in the kitchen.
The patient killed the mice and later disposed of the remains and cleaned
the trash can without wearing gloves. The family slept in the cabin that weekend
and trapped six additional mice during their stay.
On August 3, investigators from CDC and the West Virginia Department
of Health and Human Resources discovered additional live mice in the trash
can in the cabin of patient B. Openings in the walls and eaves were identified
that permitted easy entry by rodents. In all, rodents were trapped by the
investigating team during August 3-6 from three rural sites in Randolph County:
(1) the dormitory in which patient A lived and its surroundings, (2) a forest
trapping site where patient A worked the week before his illness, and (3)
the family cabin and surroundings of patient B. Fourteen white-footed mice
(P. leucopus) and one deer mouse (P. maniculatus) were captured from 239 traps during a 3-day period.
Tissue and blood specimens were collected and processed for serology. RT-PCR
was conducted on specimens of rodents with positive serology results. Hantavirus
antibodies were detected in one white-footed mouse, which was also positive
for virus RNA by RT-PCR. Sequence of the amplified RNA indicated that the
mouse was infected with Monongahela hantavirus identical to virus identified
in rodents collected from the location where patient B was presumed to have
been infected. The amplified nucleic acid sequence was similar, but not identical,
to that amplified from patient A.
Randolph County Dept of Health; J Rooney, DVM, West Virginia Dept of
Health and Human Resources. K McCombs, MPH, New River Health District, Virginia
Dept of Health. Div of Viral and Rickettsial Diseases, National Center for
Infectious Diseases; B Pavlin, MD, J Sinclair, DVM, EIS officers, CDC.
Since HPS was first identified in the southwestern United States in
1993, a total of 379 laboratory-confirmed cases of HPS have been reported
in the United States, including 32 retrospectively identified cases that occurred
before 1993. Cases have been reported in 31 states, the majority of cases
in the Southwest. Three cases of HPS have been identified as acquired in West
Virginia. Subclinical infections are rare, according to antibody prevalence
studies performed after the 1993 outbreak.5- 7
In the first case described in this report, exposure was probably occupational.
Patient A regularly handled multiple mice, often suffered bites, and reportedly
did not routinely wash his hands after handling rodents. In the second case,
the exposure was peridomestic, likely associated with contact with live mice
and their excreta while removing them from his cabin. Despite the temporal
and geographic proximity of the two cases, no common exposure source, other
than the rodent contact described, appears to exist.
These cases underscore the need to educate the public and clinicians
about the risk for HPS in areas outside the Southwest. In addition, persons
who have occupational exposure to rodents and their excreta should be trained
in proper animal handling and use of personal protective equipment. Simple,
effective methods are available to reduce exposure to hantaviruses (Box ). Adherence to these precautions can reduce the incidence
The report is based on data provided by P Keyser, PhD, MeadWestvaco
Corporation, Elkins; M Fisher, MD, Ruby Memorial Hospital, Morgantown; J Crum,
PhD, West Virginia Div of Natural Resources. M Kelly, PhD, Dept of Fisheries
and Wildlife Science, Virginia Polytechnic Institute and State Univ, Blacksburg,
Two Cases of Hantavirus Pulmonary Syndrome—Randolph County, West Virginia, July 2004. JAMA. 2005;293(4):416-418. doi:10.1001/jama.293.4.416