Download Infection With Sin Nombre Hantavirus: Clinical

Infection With Sin Nombre Hantavirus: Clinical Presentation and
Outcome in Children and Adolescents
Mary M. Ramos, MD, MPH*; Gary D. Overturf, MD*‡; Mark R. Crowley, MD*;
Robert B. Rosenberg, MD, PhD§; and Brian Hjelle, MD‡
ABSTRACT. Objective. Sin
Nombre
hantavirus
(SNV) is the leading causative agent of hantavirus cardiopulmonary syndrome (HCPS) in the United States
and Canada. Relatively few cases of HCPS have involved
children. This report describes the clinical characteristics
of a series of pediatric cases of SNV infection in the
United States and Canada from 1993 through March 2000.
Methods. We analyzed clinical and laboratory data on
13 patients who were <16 years old with SNV infection
from 1993 through March 2000 identified from a database
at the University of New Mexico.
Results. The patients ranged from 10 to 16 years of
age, with a median of 14. Fifty-four percent were female.
Fifty-four percent were Native American. The most common prodromal symptoms were fever, headache, and
cough or dyspnea (100%); nausea or vomiting (90%); and
myalgia (80%). The most common physical findings at
admission were tachypnea (67%) and fever (56%); hypotension was seen in 33% of patients. On admission, all
patients manifested thrombocytopenia (median platelet
count: 67 000/mm3) and elevated lactate dehydrogenase
(median level: 1243 IU/L), and >85% of patients had
elevated levels of serum aspartate aminotransferase, alanine aminotransferase, and hypoalbuminemia. Leukocytosis and hemoconcentration were seen in less than one
third of patients at admission. HCPS developed in 12 of
the 13 patients (92%), and 4 of those 12 died (33% casefatality ratio). The majority of HCPS patients (8 of 12
[67%]) were critically ill and required mechanical ventilation. Extracorporeal membrane oxygenation was used
in 2 patients, 1 of whom survived. An elevated prothrombin time (>14 seconds) at admission was predictive of
mortality.
Conclusions. Infection with SNV in children and adolescents causes HCPS with a clinical course and mortality rate similar to that described in adults. We believe
that early recognition of HCPS in children and adolescents and appropriate referral to tertiary care centers that
are experienced with HCPS are important in reducing
mortality. Pediatrics 2001;108(2). URL: http://www.
pediatrics.org/cgi/content/full/108/2/e27; hantavirus, children, adolescents, extracorporeal membrane oxygenation.
ABBREVIATIONS. HCPS, hantavirus cardiopulmonary syndrome; SNV, Sin Nombre hantavirus; CDC, Centers for Disease
From the *Department of Pediatrics and ‡Department of Pathology and
Tricore Reference Laboratory, University of New Mexico Health Sciences
Center, Albuquerque, New Mexico; and §Department of Pediatrics, Texas
Tech University Health Sciences Center, Lubbock, Texas.
Received for publication Jun 28, 2000; accepted Apr 4, 2001.
Reprint requests to (B.H.) Department of Pathology, University of New
Mexico School of Medicine, Albuquerque, NM 87131. E-mail:
[email protected]
PEDIATRICS (ISSN 0031 4005). Copyright © 2001 by the American Academy of Pediatrics.
http://www.pediatrics.org/cgi/content/full/108/2/e27
Control and Prevention; UNM, University of New Mexico; WBC,
white blood cell count; ECMO, extracorporeal membrane oxygenation.
H
antavirus
cardiopulmonary
syndrome
(HCPS), also known as hantavirus pulmonary syndrome, is a viral zoonotic disease. It
is characterized by a febrile prodrome progressing to
respiratory distress from noncardiogenic pulmonary
edema and in severe cases to cardiogenic shock.
HCPS is seen primarily in adults and has a casefatality ratio of 38%. The majority of deaths result
from hypoxemia and cardiac dysfunction with
marked hypotension and ventricular arrhythmias.
For this reason, some experts1 prefer the term “hantavirus cardiopulmonary syndrome” to the term
“hantavirus pulmonary syndrome.” The Sin Nombre
hantavirus (SNV) is the primary causative agent of
HCPS in the United States and Canada.
As described by the Centers for Disease Control
and Prevention (CDC),2 the HCPS prodrome typically consists of fever, chills, myalgia, headache, and
gastrointestinal symptoms. The CDC’s clinical case
definition of HCPS is a febrile illness (ie, temperature
⬎38.3°C) characterized by bilateral diffuse interstitial
edema that may radiographically resemble adult respiratory distress syndrome, with respiratory compromise requiring supplemental oxygen, developing
within 72 hours of hospitalization, and occurring in a
previously healthy person. Typical laboratory findings include hemoconcentration, thrombocytopenia,
left shift in the white blood cell count (WBC), neutrophilic leukocytosis, and circulating immunoblasts.
Laboratory criteria for diagnosis include detection of
hantavirus-specific immunoglobulin M or rising titers of hantavirus-specific immunoglobulin G, detection of hantavirus-specific ribonucleic acid sequence
by polymerase chain reaction in clinical specimens,
or detection of hantavirus antigen by immunohistochemistry.2 A few cases of SNV infection leading to
febrile illness without respiratory compromise have
been reported3–5; however, the majority of cases
progress to HCPS as described above.
Typically, the disease affects healthy adults in rural settings, where there is peridomestic or occupational exposure to aerosols of rodent excreta. The
deer mouse (Peromyscus maniculatus) is the main rodent reservoir for SNV. Most cases of HCPS have
occurred in the southwestern United States, although
confirmed cases have been reported in 30 states.6
Because relatively few cases of SNV infection have
PEDIATRICS Vol. 108 No. 2 August 2001
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involved children, the disease has been described
primarily as it occurs in adults. Since the emergence
of HCPS in 1993, 15 (5.5%) of 274 cases reported to
the CDC have involved children ⱕ16 years of age (J.
Young, Special Pathogens Branch, CDC, personal
communication, November 2000). Several case reports of children with hantavirus infection in the
United States have appeared in the literature.3,5,7–10
Because no case fatalities have been reported in children younger than 14 years, it has been hypothesized
that younger children and adolescents who are infected with SNV are less likely to develop serious
illness than are older adolescents and adults. This
report describes the clinical characteristics and outcomes of a relatively large series of pediatric cases of
SNV infection in the United States and Canada from
1993 through March 2000.
METHODS
Since 1993, the University of New Mexico (UNM) Department
of Pathology has maintained a database of hantavirus infection
cases documented with serologic testing performed at the UNM
Health Sciences Center. The database includes patients who were
seen at UNM Hospital as well as those hospitalized elsewhere.
This database was reviewed for cases of hantavirus infection
involving patients who were 16 years of age or younger. Supplemental information was obtained by medical chart review, communication with referring physicians, and in one instance from a
published case report.8
Data were extracted by 2 authors (M.M.R. and R.B.R.) using a
standardized data collection form and were analyzed using SAS
software version 6.12 (SAS Institute, Inc, Cary, NC). Correlations
between mortality and symptoms before admission, physical examination findings, or laboratory findings at admission were examined using Fisher’s exact test (2-tail) or univariate logistic regression, where appropriate. Correlations between the
development of respiratory failure and the aforementioned patient characteristics were examined similarly.
Serologic specimens were analyzed by Western blot and/or
strip immunoblot assays. Our criterion for diagnosis was the
detection of immunoglobulin M antibodies to SNV nucleocapsid
(N) antigen. In all cases, immunoglobulin G antibodies to glycoprotein G1 antigens were present as well. Antibodies to glycoprotein G1 are specific for infection with SNV and are not seen
with infections caused by other, closely related hantaviruses.11–13
TABLE 1.
Case Report
A previously healthy 11-year-old girl from rural
Arizona (patient 4 from Table 1) presented to a regional hospital emergency department with a 2-day
history of headache, myalgia, chest pain, sore throat,
and fever. She was afebrile at the time of the visit. A
throat culture was obtained, and she was discharged
to home. She returned the following day with the
same complaints and increasing shortness of breath.
There were no ill contacts and no known rodent
exposure. The patient’s medical history was unremarkable.
At the emergency department on the day of admission, she was alert and in moderate distress with
nasal flaring. She had a temperature of 39.0°C, pulse
of 140 beats/min, respiratory rate of 64 breaths/min,
Summary of Patient Cases
Patient
Number
Age
(Year)
Gender
1
16
M
White
2
14
F
3
15
F
4
11
F
5
12
M
6
13
F
7
10
M
8
15
F
9
15
M
10
11
F
11
12
F
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RESULTS
As of March 31, 2000, the hantavirus database at
UNM included a total of 175 patients with SNV
infection confirmed by serologic testing at UNM
Hospital. Of these, 13 patients (7%) were ⱕ16 years
old. Ages ranged from 10 to 16 years (median: 14
years). Four of these 13 patients died (31%). The
median age of those who died was 15 years (range:
14 –15 years) versus 12.5 years (range: 10 –16 years)
for those who survived. Seven were female (54%)
and 6 were male. Seven (54%) were identified as
Native American; 2 (15%) were Hispanic; 1 (8%) was
white; information on ethnicity was not available for
the other 3 patients.
Medical records of 11 of these 13 patients were
available for review; these patients are summarized
in Table 1. Six patients were hospitalized at UNM
Hospital, and 2 patients were hospitalized at Texas
Tech University Health Sciences Center. For these
patients, the database was most complete. The 2
patients who are not included in Table 1 died, and
their information was limited; they were 14 and 15
years old.10
Ethnicity
Level of Intervention
Received
Risk Factors (Exposure)
Outcome
Reference
TX
Mechanical ventilation
Lived
7
Hispanic
NM
Native
American
Native
American
Native
American
NM
Oxygen by nasal
canula
ECMO
Rural; rodent droppings
at home
Rural
Rural
Died
AZ
Mechanical ventilation
Lived
AZ
Observation; no
supplemental
oxygen required
Oxygen by nasal
canula
Oxygen by nasal
canula
Oxygen by nasal
canula
Mechanical ventilation
Rural; collected piñón
nuts
Rural; mice at home
Lived
Rural; mice in shed
Lived
Rural; mice in home
and family vehicle
Rural; exposure to mice
Lived
Rural
Died
Rural; mouse droppings
in home
Rural
Lived
Native
American
Native
American
Native
American
Unknown
Native
American
Hispanic
Place of
Residence
NM
NM
AZ
Alberta,
Canada
NM
TX
ECMO
Mechanical ventilation
SIN NOMBRE HANTAVIRUS INFECTION IN CHILDREN
Lived
5
Lived
Lived
8
and a blood pressure of 132/70 mmHg. Her percutaneous oxygen saturation was 61% in room air. She
had markedly decreased breath sounds bilaterally,
with mild retractions. Her abdominal examination
was unremarkable. Her WBC was 15 300/mm3, her
hematocrit was 46%, and her platelet count was
74 000/mm3. The WBC differential was 52% neutrophils, 27% lymphocytes, 13% bands, and 7% monocytes. Her chest radiograph revealed bilateral interstitial infiltrates. An initial arterial blood gas while
on 3 L/min flow of oxygen by nasal canula showed
the following: pH 7.43, pCO2 32 torr, pO2 61 torr, and
HCO3 21 mmol/L.
She was intubated before transfer to UNM Hospital with a diagnosis of possible HCPS. Gram stain of
a tracheal aspirate obtained at the time of intubation
showed few white blood cells and many Gram-negative coccobacilli and diplococci suggestive of Haemophilus influenza infection. Before her transfer, she
was treated empirically with nebulized albuterol and
intravenous methylprednisolone, ceftriaxone, gentamicin, and erythromycin.
On admission to UNM Hospital, her temperature
was 36.9°C, her heart rate was 96 beats/min, and her
blood pressure was 120/55 mmHg. Her percutaneous oxygen saturation was 94% on a volume-controlled ventilator with a positive end expiratory pressure of 5, tidal volume of 500 mL (10 mL/kg),
respiratory rate of 30, and an FIO2 of 0.60. Her physical examination was significant for tachycardia and
diffuse rales bilaterally.
A right pleural effusion and bilateral interstitial
infiltrates were present on the admission chest radiograph. Laboratory studies on admission revealed a
WBC of 11 400/mm3, hematocrit of 35%, platelet
count of 74 000/mm3, an elevated serum aspartate
aminotransferase of 109 IU/L (normal: 5–35), and
alanine aminotransferase of 71 IU/l (normal: 5–35).
Her serum lactate dehydrogenase was elevated at
1268 IU/L (normal: 300 – 600). Peripheral blood
smear analysis revealed thrombocytopenia, ⬎10%
circulating immunoblasts among the lymphoid series, and a left shift in the granulocytic series without
significant toxic changes. These features were consistent with hantavirus infection. A Western blot assay
done on admission was positive for immunoglobulin
M and immunoglobulin G antibodies against SNV.
The positive serologic finding was confirmed by
polymerase chain reaction analysis, which revealed
circulating SNV ribonucleic acid.
The sputum culture from the referring facility
grew Moraxella species. Blood and urine cultures
from the referring facility were found to be negative.
A repeat sputum culture from UNM hospital sent on
the day of admission found normal oral flora. Nasopharyngeal swabs for respiratory syncytial virus, influenza A and B, parainfluenza, and adenovirus detected by fluorescent antibodies were negative.
Antibiotics were discontinued late on the day of
admission when results from the Western blot were
available. The patient made a rapid recovery. She
was extubated to a face mask that delivered inspired
oxygen of 40% on the second hospital day and was
weaned to oxygen by nasal canula later that day. A
chest radiograph from that day found minimal residual patchy air space disease. By 2 days after her
admission, her thrombocytopenia also had resolved,
to a platelet count of 164 000/mm3.
She was transferred back to the referring hospital
on the fourth hospital day. At that time, she was
receiving oxygen by nasal canula at 1 L/min flow
with a percutaneous oxygen saturation of 91%.
Clinical Presentation
Symptoms
Among the 10 patients for whom information was
available, the mean duration of symptoms before
hospitalization was 3.5 days (median: 3.5; range:
1–7). The most common symptoms, each present in
at least 80% of patients at the time of admission,
were, in descending order of frequency, fever, headache, nausea or vomiting, cough, shortness of breath,
and myalgia (Table 2). All patients had respiratory
complaints of either cough or shortness of breath. No
patients had complaints of rhinorrhea or nasal congestion, although 4 (40%) complained of sore throat.
Signs
At the time of hospital admission, 6 (55%) of 11
patients were hypoxemic with percutaneous oxygen
saturations below 90% in room air; 2 patients required oxygen by nasal canula, and 4 patients required mechanical ventilation either before admission or shortly thereafter. The most common
physical examination findings on admission were
tachypnea and fever (Table 3). Seven patients (78%)
had respiratory findings of either tachypnea or rales
at admission. Hypotension and tachycardia were relatively uncommon findings on admission, seen in
33% and 22% of patients, respectively. No patient
had purpura or petechial rash, evidence of mucosal
bleeding, or peripheral or periorbital edema.
Laboratory Findings
Thrombocytopenia was observed at admission in
all of 11 patients (100%) for whom this information
was available (Table 4). Leukocytosis and hemoconcentration were less common, each present in 3 of 11
patients (27%). Of the 10 patients with differential
WBC at the time of admission, 6 (60%) had at least
10% band forms, 3 (30%) had metamyelocytes, and 4
TABLE 2.
Symptoms in 10 Pediatric Patients With Sin Nombre Hantavirus Infection
Symptom
Number of
Patients (%)
Fever
Headache
Nausea or vomiting
Cough
Shortness of breath
Myalgia
Abdominal pain
Back pain
Sore throat
Diarrhea
Chest pain
Chills
Dizziness or lightheadedness
10 (100)
10 (100)
9 (90)
9 (90)
8 (80)
8 (80)
5 (50)
5 (50)
4 (40)
4 (40)
3 (30)
3 (30)
3 (30)
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TABLE 3.
Clinical Findings at Time of Admission in 9 Pediatric Patients With Sin Nombre Hantavirus Infection
Sign
Number of
Patients
(%)
Tachypnea*
Fever (temperature ⱖ38.0°C)
Crackles or rales on lung exam
Abdominal tenderness
Hypotension†
Tachycardia (heart rate ⬎120 bpm)
Cool, clammy, or mottled skin
6 (67)
5 (56)
4 (44)
4 (44)
3 (33)
2 (22)
1 (11)
* Respiratory rate ⬎25 breaths/min (10 –13 years old). Respiratory
rate ⬎20 breaths/min (ⱖ14 years old). Includes 2 patients mechanically ventilated before admission.
† Systolic blood pressure ⬍95 mm Hg (10 –13 years old). Systolic
blood pressure ⬍100 mm Hg (ⱖ14 years old).
(40%) had atypical lymphocytes. Other laboratory
abnormalities commonly seen at admission included
elevated levels of lactate dehydrogenase, aspartate
aminotransferase, and alanine aminotransferase and
hypoalbuminemia (Table 4).
Three HCPS patients who were admitted to UNM
hospital had peripheral blood smear analysis. All
had thrombocytopenia, ⬎10% circulating immunoblasts, and left shift in the granulocytic series without
toxic changes.
Five patients had an initial urinalysis at the time of
admission. The median urine specific gravity was
1.029 g/mL (range: 1.013 to 1.041). Three of 5 patients
had proteinuria (ⱖ2⫹) on admission. Urine dipsticks
were positive for blood in 2 of 5 patients; microscopic
examination revealed ⬍3 red cells per high-power
field for both.
Initial chest radiographs for 10 patients revealed
interstitial or interstitial and alveolar infiltrates in 5
patients (50%), Kerley B lines or fluid in the fissures
in 2 (20%), fluffy alveolar infiltrates in 1 (10%), and
normal radiographs in 2 (20%). The 2 patients with
initial normal chest radiographs developed interstitial edema within 48 hours.
Of the 13 patients, 5 became ill during the spring,
2 in the summer, 4 in the fall, and 2 patients (patients
9 and 10 from Table 1) in the winter. The majority of
patients were previously healthy and without medical problems. One patient was taking erythromycin
at the time of admission for acne vulgaris, and another patient had a history of asthma.
Three patients were examined by medical providers and discharged to home with mistaken provisional diagnoses before returning and being admitted. All survived. Two of the 3 developed respiratory
failure and required mechanical ventilation.
Clinical Course
In 12 (92%) of the 13 patients reviewed , HCPS
developed. One patient did not have an oxygen requirement and so failed to meet the CDC clinical case
description as described previously. He was a 12year-old from a rural Arizona town and had a febrile
illness characterized by prominent abdominal pain,
nausea and vomiting, headache, myalgia, cough, and
sore throat. Because of the patient’s rural location,
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history of mice around the home, and presenting
symptoms, the patient was tested for SNV infection.
Of the 12 patients with HCPS, 4 (33%) required
oxygen by nasal canula and 8 (67%) required mechanical ventilation. For the patients who required
mechanical ventilation, the average time from the
onset of symptoms to endotracheal intubation was
3.8 days (median: 4.5; range: 1– 6). Patients who were
intubated but not treated with extracorporeal membrane oxygenation (ECMO) were intubated for an
average of 4.6 days (median: 4; range: 2– 8). Hypotension necessitating support with vasoactive infusions developed in 5 of the 10 HCPS patients for
whom this information was available.
Two patients received ECMO support for hemodynamic deterioration despite resuscitation with fluids and vasoactive medications and mechanical ventilation. ECMO therapy was initiated after 1 day and
3 days of symptoms, respectively, for the 2 patients
who received this treatment. The patient who received ECMO and survived required ECMO for 8
days and mechanical ventilation for 20 days. The
other ECMO patient died after 7 days of ECMO
support as a result of brain death caused by a prolonged cardiac arrest before ECMO initiation.
Only 1 patient developed significant bleeding during hospitalization; she developed a hemothorax as a
complication of thoracentesis for pleural effusion.
Although not common at the time of admission,
leukocytosis eventually was seen in 7 of 11 patients
(64%) during hospitalization, and hemoconcentration was seen in 6 of 11 patients (55%).
The clinical course of the 4 HCPS patients who
died was characterized by pulmonary edema, hypotension, and ventricular arrhythmias. The ECMO
case fatality was described above. One patient died
en route to a hospital, and 2 patients died despite
standard critical care. Of the group who survived,
the average hospital stay was 9.9 days (median: 8;
range: 3–28) to discharge to home or transfer (in 2
cases) to a regional hospital. Those who survived
were without sequelae.
Predictors of Mortality
An elevated prothrombin time (ⱖ14 seconds) at
admission was associated with a fatal outcome (P ⫽
.04, Fisher’s exact test). An elevated WBC (⬎13.5 ⫻
103/mm3) on admission showed only a trend toward
significance in association with mortality (P ⫽ .06,
Fisher’s exact test) as did age ⱖ14 years, the median
age of our patients (P ⫽ .07, Fisher’s exact test).
Symptoms before hospitalization, duration of symptoms, specific physical examination findings on admission including hypoxemia, and other laboratory
findings were not associated with mortality.
Predictors of Respiratory Failure
Hypotension at admission was associated with respiratory failure requiring mechanical ventilation
(P ⫽ .02, Fisher’s exact test) as was the absence of
fever at admission (P ⫽ .05, Fisher’s exact test).
Symptoms before hospitalization, duration of symptoms, other physical examination findings on admission including presence of hypoxemia, and labora-
SIN NOMBRE HANTAVIRUS INFECTION IN CHILDREN
TABLE 4.
Results of Laboratory Studies at Time of Admission in Pediatric Patients With Sin Nombre Hantavirus Infection
Number
Test
Admission Value
(Median [Range])
11
11
White cells: ⫻ 103/mm3
Hematocrit (%)
Patients 10–12 y (n ⫽ 5)
Males 13–16 y (n ⫽ 2)
Females 13–16 y (n ⫽ 4)
Platelets: ⫻ 103/mm3
Creatinine (mg/dL)
Prothrombin time (sec)
Partial thromboplastin time (sec)
Carbon dioxide (mmol/L)
Blood urea nitrogen (mg/dL)
Aspartate aminotransferase (IU/L)
Albumin (g/dL)
Alanine aminotransferase (IU/L)
Lactate dehydrogenase (IU/L)
Lactate (mmol/L)
9.0 (3.4–59.2)
11
10
9
9
9
9
8
8
7
7
6
tory findings were not associated with respiratory
failure.
DISCUSSION
In this case series of pediatric patients who were 10
to 16 years of age and infected with SNV, the clinical
outcomes did not differ greatly from those described
in adult cases. The case fatality ratio of 33% (4 of 12)
for these pediatric patients with HCPS is comparable
to the 38% case fatality rate (105 deaths in 274 cases)
described for HCPS overall in the United States (J.
Young, Special Pathogens Branch, CDC, personal
communication, November 2000). As in adult cases,
the majority of the 12 pediatric HCPS patients described herein (8 of 12 [67%]) were critically ill and
progressed to respiratory failure. Consistent with the
newer designation of hantavirus cardiopulmonary
syndrome, at least half of the patients developed
cardiogenic shock and required inotropic support.
The most frequent prodromal symptoms of our
pediatric patients, particularly fever, headache, myalgia, and respiratory and gastrointestinal complaints, are comparable to those described in adults
with HCPS. One exception is the common complaint
of sore throat, seen in almost half of our patients,
which has been described as an infrequent symptom
among adults with HCPS.14,15 Typical clinical laboratory findings early in the course include thrombocytopenia and elevated liver enzymes and lactate
dehydrogenase. A left shift in the granulocytic series
without toxic changes is often present, but leukocytosis and hemoconcentration are relatively late findings, observed in ⬎50% of cases during the course of
illness.
The differential diagnosis for pediatric patients
who present with fever, headache, myalgia, and respiratory and gastrointestinal symptoms is broad.
Viral and bacterial pneumonia, sepsis syndrome
with adult respiratory distress syndrome, and acute
gastroenteritis are among the more likely clinical
syndromes. The authors are aware of patients admitted to rule out HCPS and who subsequently had the
diagnosis of viral respiratory illness (eg, respiratory
syncytial virus), streptococcal pharyngitis, and sepsis
attributable to S aureus. Depending on the region of
42.0 (34.9–45.2)
54.3 (47.6–61)
41.9 (40–48.4)
67 (43–98)
0.7 (0.4–3.9)
13.1 (11.0–29.8)
38 (27–212)
20 (15–27)
10 (8–26)
98 (39–129)
2.8 (1.2–3.5)
55 (21–80)
1243 (382–1724)
2.5 (1.5–18.4)
North America where the patient may present and
the exposure history, the differential diagnosis may
be broad, including septicemic plague or tularemia,
ehrlichiosis, leptospirosis, Colorado tick fever, relapsing fever, or (“spotless”) Rocky Mountain spotted fever.
Because the initial prodrome is nonspecific, clinically diagnosing pediatric HCPS with either mild
disease or in the early prodrome phase presents a
diagnostic challenge. SNV infection should be considered in pediatric patients from rural areas, especially in western North America, who present with
fever, headache, myalgia, and respiratory and gastrointestinal symptoms, particularly if there is a history of possible rodent exposure. Infection is most
common from spring through fall.
If HCPS is suspected, then a complete blood count
with platelet count should be obtained. Thrombocytopenia is a key laboratory feature of HCPS. If thrombocytopenia or a rapidly decreasing platelet count is
found, peripheral blood smear analysis and serology
testing should be performed. At UNM hospital, a
peripheral blood smear with 4 of the 5 criteria
(thrombocytopenia, ⬎10% circulating immunoblasts
among the lymphoid series, left shift of granulocytic
series, without toxic changes, and hemoconcentration) has been found to have a positive predictive
value of 90% for HCPS. All cases with 5 of the 5
criteria have been confirmed serologically (K. Foucar, Department of Pathology, UNM School of Medicine, personal communication, September 2000).
Pending results, patients need to be monitored
closely for signs of cardiopulmonary compromise,
which can develop rapidly with the onset of pulmonary edema. There is not yet a reliable early indicator
as to which patients will develop more severe disease.
Because of the high proportion of HCPS patients
who become critically ill and the rapid deterioration
seen in many HCPS patients, we believe that early
transfer to a tertiary care center that is capable of
providing critical care and ECMO support should be
strongly considered. In our experience, ECMO seems
to be beneficial in the support of critically ill patients
with severe HCPS,16 including pediatric patients.
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ECMO has been used in the treatment of 26 HCPS
patients at UNM Hospital with a survival rate of 69%
(M.R. Crowley, unpublished data). Criteria for the
initiation of ECMO at UNM Hospital include parameters consistent with 100% mortality from our experience with HCPS.
CONCLUSION
HCPS is an uncommon serious viral zoonosis that
causes respiratory failure and cardiovascular instability in children and carries a high case fatality rate
of 33%. HCPS in pediatric patients has a similar
presentation and outcome to that described in adults.
HCPS occurs mainly in the rural western United
States, but cases have been reported nationwide. Because of the high mortality and often fulminant deterioration of pediatric HCPS patients, medical providers who care for children should familiarize
themselves with the clinical features of HCPS. Early
recognition of this disease with prompt referral to
tertiary care centers that have experience with HCPS
likely will improve outcome and reduce mortality.
ACKNOWLEDGMENTS
This study was supported by Public Health Service Grant RO1
AI 41692 and by the Defense Advanced Research Projects Agency.
We thank J. Rawlings, F. Koster, R. Servi, D. Goade, J. Young,
and J. Hutchinson for their help in collecting data; C. Qualls for
assistance with statistics; and TriCore Laboratories for technical
assistance.
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SIN NOMBRE HANTAVIRUS INFECTION IN CHILDREN