AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Over the past 12 years, hantavirus has become a serious concern in the United States. The disease was actually first identified during the Korean War in the early 1950s when about 3,000 US and UN forces were infected with a mysterious viral illness. The virus was named Hantaan, after the Hantaan River in Korea, and infection was associated with fever, hypotension, renal failure, thrombocytopenia, and disseminated intravascular coagulation (DIC). This clinical syndrome is known as hemorrhagic fever with renal syndrome or HFRS. Hantaviruses have been responsible for outbreaks of hemorrhagic fevers in Russia (1913), Scandinavia (1932-1935), and Finland (1945).

Hantavirus cardiopulmonary syndrome (HCPS), a similar but more virulent entity, was recognized initially on May 14, 1993. The New Mexico Office of the Medical Investigator alerted the New Mexico Department of Health to a cluster of 3 unexplained deaths occurring in the Four Corners region of the southwestern United States. (Four Corners is the intersection formed by the borders of Utah, New Mexico, Arizona, and Colorado.) Almost simultaneously, an Indian Health Service physician noted another cluster of 5 unusual deaths, also in the Four Corners region, and alerted authorities. As the cases began to accumulate, a common clinical picture emerged. Fever, chills, and myalgias accompanied disease onset, followed by cough and dyspnea, with a progression to cardiovascular collapse, respiratory failure, and death. Initial mortality rate was approximately 80% (see Image 1).

Subsequent identification and isolation of the causative organism and its vector represent one of the best examples of medical collaboration and detective work to date. Representatives from the Centers for Disease Control and Prevention (CDC) and state and local health organizations gathered and began an intensive study of the disease. They considered causes as diverse as pneumonic plague, influenza, bioterrorism, and phosphine exposure but rapidly eliminated them all.

The CDC compared serum samples from the victims to hundreds of different viruses and bacteria through fluorescent antibody testing. One victim's serum showed weak reactivity to the Puumala virus, which previously had never been observed in North America. Puumala virus is an Old World hantavirus found in Asia and northern Europe and is responsible for a form of hemorrhagic fever associated with renal failure. However, Puumala virus did not cause respiratory collapse and had not been found in North America. The weak reactivity suggested a novel hantavirus. The only known North American hantavirus was the harmless Prospect Hill virus, carried by the meadow mole and found on the East Coast. Clearly, this was a different hantavirus species.

Over the next month, the virus was isolated and extensive research identified Peromyscus maniculatus (ie, deer mouse) as the reservoir and vector for the disease (see Image 2). Within 10 weeks of the original outbreak, researchers at the CDC and the University of New Mexico (UNM) developed a diagnostic test for the virus. The new virus went through a litany of names (eg, Little Water virus, Four Corners virus, Muerto Canyon virus) before finally being given the somewhat tongue-in-cheek moniker of Sin Nombre virus (in Spanish, literally the virus with no name). The clinical syndrome caused by Sin Nombre virus (SNV) became known alternatively as hantavirus pulmonary syndrome (HPS) or, more accurately, hantavirus cardiopulmonary syndrome (HCPS).

Hantaviruses are responsible for 2 distinct clinical entities: HCPS and HFRS. Both are associated with a primary rodent reservoir. Human infection occurs by inhalation of rodent urine, feces, and saliva. Old World viruses cause HFRS. Cases of HFDS occur worldwide, including large sections of Asia and Europe. In China alone, approximately 100,000 cases of symptomatic HFRS occur each year. It is now understood that HFRS can be caused by any of the Old World hantaviruses including Seoul virus, Dobrava virus, and Puumala virus.

Presently, 13 New World hantaviruses are known. Four of these cause HCPS in North America. SNV is the prototypical New World hantavirus and the cause of the vast majority of cases of HCPS in the United States (see Image 3). Other New World hantaviruses have caused at least 6 cases of HCPS. Cases of HCPS in the Southeastern United States have been linked to the Black Creek Canal virus and the Bayou virus. These cases differ from HCPS caused by SNV by being associated with renal failure. New York virus (also called Shelter Island virus or Rhode Island virus) is similar in structure and clinical effect to SNV.

The other large reservoir for New World hantavirus is South America, where at least 4 pathologic viruses have been described. One of these, the Andes virus of Argentina and Chile, is implicated in person-to-person transmission and is reported to carry a high pediatric and infant mortality rate. Like those of the Bayou and Black Creek Canal viruses, the Andes virus syndrome has a high incidence of renal failure and other symptoms more characteristic of HFRS than HCPS.

HCPS has probably existed in North America's southwest desert for hundreds, if not thousands, of years. Navajo oral tradition tells of an illness similar to HCPS that strikes down young healthy members of the tribe after temperate winters and warns of the dangers of coexisting with rodents. Navajo elders speak of 2 epidemics that struck the region in 1917-18 and 1934; however, the former may represent the influenza pandemic of 1918. The earliest case of a serologically confirmed SNV infection was in a person who developed an HCPS-like illness in July of 1959 and was found to have immunoglobulin G (IgG) antibodies to SNV in September of 1994.

Pathophysiology

Pathophysiology of HCPS is complex. Infection occurs by inhalation of aerosolized virus from feces, urine, or saliva of infected rodents. Although hantaviruses have been shown to replicate in cultured human endothelial cells, considerable evidence exists that immune mechanisms rather than direct viral cytopathology are responsible for the vascular dysfunction resulting in plasma leakage in HFRS and HCPS.

Hantaviruses preferentially infect endothelial cells. Endothelial cells in the kidney are the targets for HFRS. In the case of HCPS, viral antigens accumulate in the pulmonary microvasculature and in the follicular dendritic cells of the spleen and lymph nodes, initiating a cascade of events culminating in a massive, pulmonary-specific immune response. This damage to pulmonary microvascular endothelium increases capillary permeability and leads to fulminant pulmonary edema. Both a decreased pulmonary artery occlusion pressure and a high level of protein in the alveolar fluid reflect the degree of capillary leakage.

Central to the pathogenesis of HCPS is the release of a yet unidentified myocardial depressant. This depressant, possibly cytokine mediated, causes cardiogenic shock with an elevated systemic vascular resistance. This cardiogenic depression is synergistic with hypovolemia secondary to a capillary leak, resulting in precipitous cardiopulmonary collapse. The name change from hantavirus pulmonary syndrome to cardiopulmonary syndrome reflects the key contribution to morbidity and fatalities made by this myocardial factor.

Frequency

United States

As of December 7, 2000, a total of 277 cases of HCPS had been confirmed in 31 states (see Image 4). The majority of these cases are believed to have been caused by SNV and have occurred west of the Mississippi River, which corresponds to the geographic distribution of the deer mouse (see Image 5).

The preponderance of cases occurs in rural locales. However, case-control studies of the original outbreak in the Four Corners region suggest that the prevalence of hantavirus infection in deer mice in and around urban and rural homes was 27.5-32.5%. The greatest concentration remains in the Four Corners area. Northern Idaho, the Dakotas, eastern Washington, and Mono County, California, also have reported cases and could be considered hot spots. National annual incidence in nonepidemic years is about 20-30 cases (see Image 6). The New York virus, the Black Creek Canal virus, and the Bayou virus have been confirmed in at least 6 cases in the eastern and southeastern United States.

Generally, outbreaks of hantavirus occur in the spring and fall. This appears to correspond with the farming cycles, by which farmers are exposed to rodents in the fields during planting and harvest periods.

International

Dozens of cases of HCPS have been reported in Canada, the majority in Alberta. Outside of North America, South America is the only other reservoir of HCPS. Confirmed cases of HCPS number 108 in Argentina, 34 in Paraguay, 27 in Chile, and 6 in Brazil. Currently, at least 4 Hantavirus species in South America are recognized to cause HCPS. One of them, Andes virus, is unique for reports of person-to-person transmission and of an increased mortality rate in children.

Mortality/Morbidity

During the 1993 outbreak in the Southwestern United States, the mortality rate was approximately 80%. Presently, in part because of increased recognition of the disease and more aggressive intervention (eg, extracorporeal membrane oxygenation, early mechanical ventilation), the rate has fallen to approximately 38%. When the cases from the initial 1993 outbreak are factored out, the proportion of deaths drops to 30%. A sobering reflection of the fulminant nature of HCPS is that most deaths occur within 24 hours of hospital admission.

Race

During the initial outbreak in 1993, Native Americans were affected disproportionately by HCPS. The press, somewhat disparagingly, termed the mysterious disease "Navajo flu." As cases mounted, however, it became clear that HCPS was an equal opportunity killer. To date, 77% of patients with Hantavirus have been white, 20% Native American, 2% African Americans, 1% Asian, and 11% Hispanic (ethnicity considered separately from race).

Sex

Males account for 60% of the total number of HCPS diagnoses. This may reflect a higher environmental exposure to deer mice.

Age

HCPS has a remarkable predilection for affecting relatively young, healthy adults. The mean age of patients with HCPS is 38 years, with a range of 10-75 years. Preadolescent children infected with SNV have suffered only mild illness and have not required intubation. One case was reported of a 4-year-old child with mild SNV infection who experienced only mild upper respiratory infection symptoms and otitis. The Andes virus of Argentina and Chile, however, reportedly carries a high risk of death in children younger than 10 months.

CLINICAL

Section 3 of 11  

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• Clinical
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• Workup
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• Follow-up
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History

The clinical course of HCPS can be divided into several discrete phases. Following an incubation period of 2-3 weeks, the patient experiences a prodromal phase marked by fever, chills, and myalgias. This phase lasts 3-10 days. Sudden onset of noncardiogenic pulmonary edema and resultant hypoxemia, dyspnea, and tachycardia heralds the cardiopulmonary phase of HCPS. Clinical deterioration during this phase is precipitous; within 24 hours patients with severe disease show signs of hemodynamic compromise. Mean time from onset of symptoms to cardiopulmonary failure is 5 days. Among survivors, recovery may be almost as rapid as decline and is accompanied by a period of diuresis. During the convalescent period, the patient often recovers with little or no residual deficits. Often, several months of fatigue and decreased exercise tolerance are the only sequelae.

Early diagnosis often is difficult, as the most common symptoms of HCPS often overlap with those of other, less ominous, viral illnesses.

• Consider diagnosis of HCPS in patients with the following:
• • Fever
  • Severe myalgias (often in the back and legs)
  • Exposure to mice or mouse droppings
• Other symptoms may include the following:
• • Cough
  • Malaise
  • GI symptoms such as nausea and vomiting, diarrhea, and abdominal pain
• Risk factors to seek in the history include the following:
• • Peridomestic rodent infestation
  • Entering or disturbing seasonally closed or infrequently opened buildings
  • Occupational exposure to rodents
• Risk also varies with rodent abundance and distribution, which in turn depends on several factors, including the following:
• • Geographic region (especially the Southwest)
  • Seasonality (increased in spring and summer)
  • Weather patterns (Outbreaks may follow El Ñino conditions of a temperate wet winter.)
• The most common prodromal symptoms are the following:
• • Fever
  • Chills
  • Myalgias (often in the back and legs)
• Other common prodromal symptoms include the following:
• • Nausea/vomiting
  • Diarrhea
  • Headache
  • Cough (usually nonproductive)
  • Malaise
  • Dizziness
  • Dyspnea (usually not observed at presentation but often heralds the cardiopulmonary phase of HCPS)
• Consider another diagnosis with the following symptoms:
• • Sore throat
  • Rhinorrhea
  • Purulent conjunctivitis
  • Rash
  • Coryza
  • Otalgia

Physical

Physical findings vary substantially with the stage of disease at presentation.

• Most frequent initial physical findings in HCPS
• • Tachypnea
  • Fever
  • Tachycardia
• Crackles or decreased breath sounds in most patients on lung exam
• Abdominal tenderness
• • Present in about 10% of patients
  • May be severe (One patient actually was taken to the OR for an appendectomy before HCPS was recognized.)
• Petechiae not observed despite thrombocytopenia
• Hallmarks of the cardiopulmonary phase of HCPS
• • Hypotension
  • Respiratory distress

Causes

In the United States, HCPS is caused by inhalation of aerosolized virus from dried excreta and urine of infected rodents.

• The vector of SNV is the deer mouse, P maniculatus. SNV causes no obvious harm to the mice. The case rate of HCPS closely parallels the distribution and number of infected deer mice. Deer mouse population increases in the right environmental conditions.
• • The 1993 outbreak was thought to be caused by the El Ñino conditions of a wet, mild winter.
  • The wet, mild winter allowed for a record season for piñon (a favorite food supply for mice) and a tenfold increase in the number of deer mice in the Four Corners region.
  • Increased rodent density also increased the percentage of infected mice. Thirty percent of deer mice in the Four Corners region tested positive for SNV in the 1993 outbreak.
• The greatest risk factor for infection is living in a domicile infested with rodents. Entering rarely opened or seasonally closed buildings also may contribute to infection. In one case-controlled study, 70% of subjects were exposed while cleaning homes or buildings that showed evidence of rodent infestation.
• Occupationally acquired HCPS has been recognized but is infrequent. Occupations at greatest risk for exposure are as follows:
• • Grain farmers
  • Agricultural workers
  • Feedlot employees
  • Field biologists

DIFFERENTIALS

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Other Problems to be Considered

Influenza
Pneumonic plague
Tularemia
Phosphine toxicity
Anthrax
Silent myocardial infarction
Salicylate toxicity with pulmonary edema

WORKUP

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Lab Studies

• Laboratory results vary with the phase of disease.
• • In the prodromal phase, CBC findings may be normal or show slight thrombocytopenia.
  • Aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) are elevated commonly during the prodromal phase of HCPS. Levels often are elevated 2-5 times reference values in this phase.
  • Elevated hematocrit (HCT), increased lactate, and consequent acidosis are late findings with ominous implications.
• CBC with peripheral blood smear is the most helpful lab examination in the diagnosis of HCPS and should be obtained in any patient with fevers, chills, or myalgias who also has any history of exposure to rodents. If initial platelet count is >150 x 10⁹/L, repeat the CBC in 12-24 hours.
• • Platelets: A falling platelet count is the only laboratory finding that reliably precedes the cardiopulmonary phase of HCPS. In patients with HCPS, 98% present with a platelet count <150 x 10⁹/L and all patients eventually develop a platelet count <100 x 10⁹/L. A dramatic fall heralds the cardiopulmonary phase of HCPS.
  • WBC: Though often eventually elevated, initial WBC is an insensitive marker of HCPS and a poor indicator of severity. Counts in confirmed cases of HCPS have varied between 2.8 and 100 x 10⁹/L. More importantly, a left shift of the myeloid line (ie, myelocytes, promyelocytes) and characteristic immunoblasts (ie, circulating atypical lymphocytes with a deep blue cytoplasm on the peripheral smear) are seen (see Image 7).
  • HCT: Hemoconcentration due to capillary leak, reflected by an elevated HCT >50% in men and >48% in women, occurs during the cardiopulmonary phase of HCPS and is a marker of severe disease. This occurs, however, in only 50% of cases.
• Prothrombin time (PT), activated partial thromboplastin time (aPTT): Levels usually are within the reference range in SNV infection. However, cases of disseminated intravascular coagulation (DIC) have been associated with HCPS.
• Arterial blood gases (ABGs): Progressive metabolic acidosis and severe hypoxemia mark the cardiopulmonary phase of HCPS.
• Creatine phosphokinase (CPK): Level usually is within reference range in HCPS caused by SNV but is elevated in infections by Bayou, Black Creek Canal, and Andes viruses.
• Creatinine: SNV causes renal failure infrequently. The Black Creek Canal, Bayou, and Andes viruses characteristically have much higher rates of renal involvement.
• Lactate: Levels as high as 9.5 mg/dL have been recorded in severe HCPS. The generally late and ominous finding of lactate > 4 has been associated with a very high mortality rate.
• Serologic assays: Definitive diagnosis of HCPS is made on the basis of 1 of 3 assays.
• • Enzyme-linked immunosorbent assay detects circulating immunoglobulin M (IgM) and IgG antibodies to SNV.
  • Western blot and strip blot assays are the most commonly used. They use a nucleocapsid (N) antigen for the detection of Hantavirus antibodies, which is universally recognized in all the patients with Hantavirus infection.
  • Also available to detect acute infection is the rapid immunoblot strip assay (RIBA). Developed by UNM, RIBA is a dipstick-type test that detects SNV antibodies in the clinical phase of the disease with 100% sensitivity.

Imaging Studies

• On initial chest x-ray (CXR), approximately one third of patients show evidence of pulmonary edema. Within 48 hours, virtually all patients demonstrate interstitial edema and two thirds have developed severe bilateral airspace disease. Though CXR findings are usually normal during the prodromal phase, onset of the cardiopulmonary phase brings about a characteristic radiologic evolution (see Image 8).
• • Mild interstitial pulmonary edema, with Kerley B lines and peribronchial cuffing, rapidly progresses to severe bilateral alveolar edema, with a basilar or perihilar pattern.
  • Pleural effusions commonly are observed late in the course of the disease.
  • Heart size usually is normal.
• Echocardiogram rarely may be helpful in differentiating HCPS from silent myocardial infarction (MI) or acute respiratory distress syndrome (ARDS), 2 important entities that may present with similar symptoms.
• • Generally see more of a global process than the more localized dysfunction caused by MI
  • In ARDS, one would expect to see normal cardiac function.

Other Tests

• ECG: Sinus tachycardia, observed early in the cardiopulmonary phase, may progress to the following:
• • Ventricular fibrillation
  • Ventricular tachycardia
  • Pulseless electrical activity (PEA); most patients who succumb to the disease die in PEA.

Procedures

• A flow-directed pulmonary artery catheterization (PAC), or Swan-Ganz catheter, is vital to direct fluid resuscitation in severe HCPS. Place the device early in the course of the disease.
• • PAC gives valuable diagnostic and prognostic information.
  • HCPS demonstrates a characteristic hemodynamic profile.
  • A low pulmonary artery occlusion pressure (consistent with a pulmonary capillary leak) and a low cardiac index characterize early HCPS.
  • Advanced HCPS is consistent with a severe drop in cardiac index and an increased systemic vascular resistance index (SVRI).
  • Prior to the use of extracorporeal membrane oxygenation (ECMO) as a rescue therapy, a cardiac index of less than 2.5 L/min/m² predicted 100% mortality rate.

TREATMENT

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Prehospital Care

Prehospital care of HCPS is supportive.

• Aggressive fluid resuscitation with crystalloids.
• Administer oxygen by nasal cannula, Venturi, or nonrebreather mask.
• Intubation is warranted for severe respiratory distress.
• Rapid transfer to a tertiary care center with ICU capabilities is of paramount importance.
• Ensure that full respiratory and standard precautions are in place for any patient whose distress may have an infectious cause.

Emergency Department Care

ED management of HCPS depends on the stage of the disease. In prodromal HCPS, the ED physician's main responsibility is to diagnose and admit for close observation. In cases of advanced HCPS, aggressive resuscitation and transfer to an ICU are the paramount concerns. Resuscitate the patient in the familiar ABC fashion.

• Airway/breathing: Administer oxygen by facemask or nonrebreather.
• • Intubate patients in respiratory failure.
  • Be aware, however, that the patient's hemodynamic status may decline precipitously after intubation.
• Circulation: Aggressive fluid resuscitation with crystalloids is indicated for any sign of hemodynamic compromise.
• • Obtain good intravenous (IV) access.
  • A few caveats are necessary if ECMO is a possibility. Avoid placing central lines in the right subclavian and right internal jugular veins. Also spare at least 1 femoral vein. These veins are used for venous access for ECMO.
• Circulation: Employ vasoactive infusions early and liberally.
• • Dobutamine is the preferred inotrope, with dopamine added as necessary to maintain blood pressure.
  • Patients with HCPS may require large doses of pressors to maintain a stable blood pressure.
• Broad-spectrum antibiotics are indicated for all patients presenting with respiratory distress and fever.
• • A third-generation cephalosporin and an aminoglycoside are a good start.
  • Consider adding a fluoroquinolone for Legionella species and chloramphenicol if pneumonic plague is in the differential diagnosis.
  • Ribavirin, though not shown to be efficacious in HCPS, may be administered under a research protocol coordinated by the CDC and UNM.
• Employ strict universal precautions.

Consultations

Patients with suspected or confirmed HCPS require ICU admission.

• Consult a medical intensivist as early as possible.
• If at an institution with adult ECMO capabilities, consult the ECMO team and vascular surgeons early for catheter placement.

MEDICATION

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Currently, no Food and Drug Administration-approved antiviral drugs, vaccines, or immunotherapeutic agents are available. Ribavirin may be effective in improving survival and hastening recovery from HFRS caused by Hantavirus when administered early. Although it has good in vitro activity against SNV, its use in the 1993 outbreak showed no benefit. A ribavirin trial in the United States did not support the use of the drug in fully developed HCPS. Additionally, some data suggest that a strong neutralizing antibody response may be a predictor of effective clearance of the SNV infection, which lends credibility to the use of passive immunotherapy in HCPS.

Liberally employ inotropes, especially dobutamine, to maintain cardiac output. Employ high-dose vasopressors for hypotension secondary to severe disease. Initiate broad-spectrum antibiotics, because bacterial pneumonia with sepsis is much more common than HCPS.

Drug Category: Inotropes

These drugs augment both coronary and cerebral blood flow present during low flow states.

Drug Category: Antivirals

These agents inhibit or reduce severity of viral infections.

FOLLOW-UP

Section 8 of 11  

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Further Inpatient Care

• Patients with confirmed or strongly suspected HCPS should be admitted to an ICU.
• Maintain oxygenation and protect the airway.
• • Intubate patients in respiratory distress.
  • Be prepared for possible hemodynamic deterioration.
• Ventilator management
• • Patients with HCPS often require high positive end-expiratory pressure (PEEP) and high fraction of inspired oxygen (FIO₂).
  • Successful ventilator strategies include pressure-limited ventilation and inverse inspiration/expiration (I/E) ratio ventilation.
• Maintain mean arterial pressure greater than 70 mm Hg, if possible.
• • Employ vasoactive infusions early (ie, dobutamine, dopamine, epinephrine, norepinephrine).
  • High vasoactive infusion rates and even boluses may be required to maintain blood pressure.
• Direct fluid management by pulmonary artery catheter placement. Avoid fluid overload by maintaining pulmonary artery occlusion pressure (PAOP) below 12 mm Hg.
• Extracorporeal membrane oxygenation
• • Pioneered by physicians at the UNM Hospital (UNMH), venoarterial ECMO has shown promise in stabilizing cardiopulmonary status in patients with severe HCPS.
  • HCPS is almost unique in its fulminant and profound cardiovascular and respiratory collapse followed by relatively rapid clinical improvement in survivors.
  • ECMO supports the failing heart and lungs long enough to allow for recovery.
  • UNMH is the only major clinical center with experience and facilities for ECMO for HCPS.
  • Presently, ECMO is a rescue therapy for use on patients who have a predicted 100% mortality rate.
  • Patients with prolonged cardiac arrest or patients in whom prolonged cerebral hypoxia is suspected are not candidates for ECMO.
  • To date at UNMH, 15 patients have been placed on ECMO. Nine have survived. Survivors have had no serious residual deficits.

Transfer

• Most cases of HCPS occur in rural communities, which may lack the facilities for aggressive intensive care. Given the precipitous deterioration of the patient, several points are important.
• • Transport early: A patient who subsequently "rules out" at a tertiary care center is preferable to a patient who deteriorates suddenly and dies en route.
  • Transport quickly: Use the fastest and best-equipped transport, which may be a fixed-wing aircraft, rotor, or ground transportation, depending on proximity.
  • Transport to the highest level care center possible: Again, anticipate the need for high-level intensive care. Severe cases may require ECMO, which principally is available at the UNMH.
  • Prepare for clinical decline en route: Anticipate administering aggressive fluid replacement and pressors.

Deterrence/Prevention

• The best way to prevent HCPS is to avoid all exposure to rodents, especially deer mice, and their excreta.
• • Tips on rodent-proofing homes indoors and out may be found at All About Hantaviruses - Prevention Indoors and Outdoors.
  • Never sweep or vacuum rodent-infested areas as this further aerosolizes the virus. Instead, wet the area thoroughly with disinfectant before cleaning, wearing rubber gloves. Other tips on cleaning infested areas may be viewed at All About Hantaviruses - Clean Up Infested Areas, Using Safety Precautions.
  • Homes with heavy infestations or homes of patients with confirmed HCPS require special precautions for cleaning. Contact the local health department for guidance. CDC recommendations may be found at All About Hantaviruses - Special Precautions for Homes of Persons with Confirmed Hantavirus Infection or Buildings with Heavy Rodent Infestations.
  • Persons who frequently handle or are exposed to rodents (eg, mammalogists, pest-control workers) in the affected area are probably at higher risk for Hantavirus infection than the general public because of their frequency of exposure. Therefore, enhanced precautions are warranted to protect them against Hantavirus infection. These precautions may be found at All About Hantaviruses - Precautions for Workers in Affected Areas Who are Regularly Exposed to Rodents.
• Vaccines
• • Presently, no vaccines are approved for use in the United States. However, researchers in Asia have made inactivated Hantavirus vaccines made from inactivated rodent brain-derived virus similar to those used to prepare Japanese encephalitis virus and rabies vaccine. A Korean inactivated vaccine called Hantavax illustrated some effectiveness in protecting mice and humans from HFRS.
  • In one study group, ELISA antibody seroprevalence was 100% after 3 vaccinations. No serious adverse side effects from the vaccine have been documented since initial use 10 years ago, which suggests its relative safety.

Complications

• Potential acute complications of HCPS include death, cardiovascular collapse, respiratory failure, anoxic brain injury, renal failure, PEA, ventricular tachycardia, and ventricular fibrillation.
• ECMO for hemodynamic or respiratory stabilization in severe HCPS
• • ECMO has its own set of potential complications, which include massive hemorrhage, sepsis, renal failure, and limb ischemia.
  • ECMO is reserved as a rescue therapy for patients who are deteriorating despite maximal conventional medical therapy.

Prognosis

• HCPS currently carries a case mortality rate of 38%. Preadolescents seem to experience a milder form of the disease and have had no reported deaths in the US.
• Experiences with HCPS at the UNMH have identified several factors that resulted in a 100% mortality rate in several patients who do not receive ECMO. These include the following:
• • Cardiac index less than 2.5 L/min/m²
  • Ventricular tachycardia, ventricular fibrillation, or PEA
  • Hypotension despite adequate fluid resuscitation and vasoactive pressors

Patient Education

• Educate patients and, more importantly, their families regarding the following:
• • Prodromal symptoms of HCPS
  • Risk of transmission by contact with rodents or rodent excreta
  • Clean-up of infested areas and rodent control measures (See Deterrence/Prevention.)

MISCELLANEOUS

Section 9 of 11  

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Special Concerns

• HCPS in pregnancy: The only 2 known cases of HCPS in pregnant women revealed the following:
• • The first went on to recover; however, the baby was born 2 months prematurely and died when aged 6 months from complications of anoxic brain injury sustained in utero.
  • The second patient died, although the baby was delivered and suffered no sequelae.
  • No evidence of vertical transmission of the disease has been found; however, the cardiovascular insult caused by HCPS carries a high fetal mortality rate.
  • The best therapy is simply good supportive care for the mother.
  • SNV is found in the breast milk of infected mothers, but transmission by breastfeeding has not been documented.
• Pediatric HCPS
• • The youngest case of HCPS in the US was in a child aged 10 years.
  • However, a serologically proven SNV infection has been reported in a child aged 4 years who experienced only upper respiratory symptoms and otitis.
  • Preadolescent children in the US typically have experienced a milder form of the disease and have not required intubation. This may be due, at least in part, to an altered immune response to the infection in children.
  • In South America, however, cases of HCPS caused by the Andes virus reportedly carry a high infant and pediatric mortality rate.

MULTIMEDIA

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Media file 1:  Hantavirus cardiopulmonary syndrome (HCPS) precautions during the 1993 outbreak
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Media file 2:  Peromyscus maniculatus - The deer mouse
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Media file 3:  Geographic distribution and viral cause of Hantavirus cardiopulmonary syndrome (HCPS)
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Media file 4:  Hantavirus cardiopulmonary syndrome (HCPS) cases by state
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Media file 5:  Geographic distribution of Hantavirus cardiopulmonary syndrome (HCPS) and Peromyscus maniculatus
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Media file 6:  Hantavirus cardiopulmonary syndrome (HCPS) yearly case rate and outcome
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Media file 7:  Hantavirus cardiopulmonary syndrome (HCPS) immunoblast
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Media file 8:  Chest x-ray progression of Hantavirus cardiopulmonary syndrome (HCPS)
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Media type:  X-RAY

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

• CDC. All About Hantavirus Website. [Full Text].
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Article Last Updated: Apr 3, 2006