Hantavirus pulmonary syndrome (HPS), known as hantavirus, is a pulmonary syndrome that is characterized by pulmonary edema, hypoxia, and hypotension. It is preceded by vague flu-like symptoms or can involve hemorrhagic fever and renal syndrome (HFRS). This is commonly due to exposure of mice feces or urine within 1 to 3 weeks of symptom onset. Hantavirus is most common in the Southwest United States and South America. HFRS has a larger incidence in Asia and Europe. The virus is transmitted by inhalation of dried rodent excrement but also may be transmitted by a rodent bite.
Hantavirus is a viral zoonosis that is most commonly found in the southwestern United States, South America, Europe, and Asia. It has been linked to hemorrhagic fevers, acute respiratory distress syndrome (ARDS), and renal failure. Hantavirus is an RNA virus of the family Bunyaviridae. Hantaviruses were first discovered in the early 1950s in soldiers of the Korean War and named Hantaan because of the nearby Hantaan River where most cases occurred. The most common virus strain in North America is Sin Nombre virus which is predominantly transmitted by the deer mouse (Peromyscus maniculatus) in the southwestern United States. This particular virus was found after a cluster of hantavirus cases occurred in 1993. Hantavirus was found in the United States in 1977, with at least 10 distinctive serotypes identified. Each serotype belongs to a specific rodent vector, geographic distribution, and clinical manifestation. Most hantavirus serotypes have a renal predilection.
Hantavirus, like other viruses in the Bunyaviridae family, have a lipid envelope around 3 RNA segments, but they chronically infect rodents instead of the usual arthropod vectors. Hantaviruses can be found wherever one can find Muridae rodents. Sigmodontinae are host to the Sin Nombre virus and are the largest group of rats and mice in the western hemisphere.
The cardiopulmonary syndrome is the primary form of Hantavirus syndrome in the United States. Europe and Asia more commonly have hemorrhagic fever with renal insufficiency syndrome.
In the United States, sporadic cases of hantavirus have been seen as far east as Maine, but the vast majority of the 697 cases as of January 2017 were west of the Mississippi River. Seven states account for approximately 70% of all cases reported in the United States: with the most cases in New Mexico (109 cases), Colorado (104 cases), Arizona (77 cases), California (63 cases), Washington (47 cases), Texas (42 cases), and Montana (41 cases).
The following list of HFRS presentations contains the virus serotype, specific rodent vector, and geographic distribution.
The following list of Hantavirus presentations contains the virus serotype, specific rodent vector, and geographic distribution.
It is suggested that around 50% of infections are due to exposure in or around the home, 10% from the workplace and 5% during recreation. The rest of the exposures are from mixed or unknown causes.
Hantavirus and HFRS are both considered to be immunopathologic.
Hantavirus begins with a prodromal phase of approximately 3 to 4 days of vague, flu-like symptoms. Nausea, vomiting, thrombocytopenia, dizziness, and dyspnea without a cough may help distinguish hantavirus from acute respiratory distress syndrome or other atypical and viral types of pneumonia. After the prodromal phase, there can be rapid development into hantavirus characterized by pulmonary edema, hypoxemia, tachycardia, and hypotension. This often occurs within 48 hours and rapid turns to respiratory failure. Patients often will develop metabolic acidosis due to the severe infection. Orthostatic hypotension can quickly progress to cardiogenic shock with cardiovascular decompensation. Patients with renal disease could develop oliguria followed by diuresis. Pulmonary auscultation may demonstrate rales. Descent into the pulmonary syndrome carries a mortality rate of around 50% to 70%.
Hantavirus hemorrhagic fever and renal syndrome have five distinct phases: Febrile, Hypotensive, Oliguric, Polyuric, and Convalescent. The incubation period is approximately 2 to 4 weeks and starts abruptly with a high fever, headache, vomiting, abdominal pain, and back pain often associated with blurred vision and somnolence. The high fever is typically present for 3 to 7 days and ends with conjunctival hemorrhages and palatal petechiae. Hypotension is then present for the next several hours to 2 days with approximately one-third of HFRS deaths due to fulminant, irreversible shock during this phase. If the hemorrhagic disease becomes severe, bleeding may present as hematemesis, epistaxis, melena, hematuria, and possibly fatal intracranial hemorrhages. Oliguria will last for 3 to 7 days with a transient decrease in renal function accompanied by back or abdominal pain that may need dialysis. Approximately half of the deaths from HFRS occur during the oliguric phase. The polyuric phase is a positive prognostic sign with evidence that renal function is improving and urinary output will increase up to several liters per day. Full recovery with return to baseline clinical and laboratory markers is reached over the next 6 months without significant long-term complications. These phases are often less severe in pediatric patients.
Chest X-ray may demonstrate bilateral pulmonary edema on the initial radiograph in about one-third of patients. Nearly all patients will have findings of interstitial edema at 48 hours after admission. Almost two-thirds of patients will develop bibasilar opacities or perihilar opacities with some degree of pleural effusions.
Thrombocytopenia may be present on blood count once admission is necessary due to the staging of the disease. Another critical laboratory finding is that of circulating immunoblasts, atypical lymphocytes, and elevated hematocrit. Once staging necessitates hospitalization, a peripheral blood smear may demonstrate myelocytes, metamyelocytes, and promyelocytes with severe thrombocytopenia and hypocapnia. Hyponatremia may also be present along with slightly prolonged activated partial thromboplastin time, a decreased protein level, mildly elevated low-density lipoprotein level, and microscopic hematuria.
Diagnosis can be made by immunofluorescent or immunoblot assay. ELISA utilizing IgM is preferred. Virus isolation, however, is not useful due to the low yield despite demonstrating easy detectability by quantitative polymerase chain reaction (PCR).
Acute Respiratory Distress Syndrome (ARDS)
Viral Hemorrhagic Fevers
By the time a patient requires hospitalization, transformation into the second stage of the disease (cardiopulmonary compromise or hemorrhagic fever with renal insufficiency) has already developed. A cough and vomiting may dominate the clinical presentation at this point. Orthostatic hypotension, tachycardia, and tachypnea will likely all be present. The first significant abnormal laboratory test, which is also the most useful, is platelet count. Thrombocytopenia or decreasing platelet count warrants admission to the hospital for further evaluation.
Despite appropriate treatment in the ICU, around one-third of patients will die in the first 48 hours after admission. Almost half of the patients admitted with Hantavirus will not require mechanical ventilation via intubation if appropriately managed with judicious fluids and close monitoring.
Should patients improve within the first few days, there is a good probability of extubation within the first week, and often there are no major long-term complications. Subjective complaints of dyspnea, fatigue, and myalgias may occur.
Higher titers of antibodies neutralizing the viral nucleocapsid immune complexes correlate with a higher likelihood of survival.
Significant long-term complications of Hantavirus or HFRS are rare; however, short-term complications, including death, have a high incidence.
Prevention is best approached by minimizing human-rodent contact. Pest control and removal of mice from living areas are key. Ventilating homes and allowing natural light into the area for neutralization of the virus by ultraviolet light may prevent the spread of the infection. Minimize food available for rodents. When disposing of dead rodents, carefully handle them using air filtration and gloves.
A vaccine produced in Asia demonstrates protective immunity but requires frequent booster administration for effect. There is no vaccine utilized in Europe or the United States outside of clinical trials.