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Hantavirus pulmonary syndrome

Hantaviruses belong to the bunyavirus family of viruses. There are 5 genera within the bunyaviridae family: bunyavirus, phlebovirus, nairovirus, tospovirus, and hantavirus. Each is made up of negative-sensed, single-stranded RNA viruses. All these genera include arthropod-borne viruses, with the exception of hantavirus, which is a genus of rodent-borne agents. more...

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The word hantavirus is derived from the Hantaan River, where the Hantaan virus (the etiologic agent of Korean hemorrhagic fever) was first isolated. The disease associated with Hantaan virus is called Korean hemorrhagic fever (a term that is no longer in use) or hemorrhagic fever with renal syndrome (HFRS), a term that is accepted by the World Health Organization.

History

Hantaviruses are a relatively newly discovered class of virus; the disease entity HFRS was first recognized by Western medicine during the Korean War in the early 1950s. In 1993, a newly-recognized species of hantavirus was found to be behind the Hantavirus cardiopulmonary syndrome (HCPS, also called HPS) caused by the Sin Nombre virus in New Mexico and other Four Corners states. In addition to Hantaan virus and Sin Nombre virus, several other hantaviruses have been implicated as etiologic agents for either HFRS or HCPS.

Geographic distribution and epidemiology

Regions especially affected by HFRS include China, the Korean Peninsula, Russia (Hantaan, Puumala and Seoul viruses), and northern and western Europe (Puumala and Dobrava viruses). Regions with the highest incidences of HCPS include Patagonian Argentina, Chile, Brazil, the United States, Canada, and Panama, where a milder form of disease that spares the heart has been recognized. The two agents of HCPS in South America are Andes virus (also called Oran, Castelo de Sonhos, Lechiguanas, Juquitiba, Araraquara, and Bermejo viruses, among many other synonyms), which is the only hantavirus that has shown (only in a few clusters of cases) an interpersonal form of transmission, and Laguna Negra virus, an extremely close relative of the previously-known Rio Mamore virus. In the U.S., minor causes of HCPS include New York virus, Bayou virus, and possibly Black Creek Canal virus.

Virology

Like other members of the bunyavirus family, hantaviruses are enveloped viruses with a genome that consists of three single-stranded RNA segments designated S (small), M (medium), and L (large). All hantaviral genes are encoded in the negative (genome complementary) sense. The S RNA encodes the nucleocapsid (N) protein. The M RNA encodes a polyprotein that is cotranslationally cleaved to yield the envelope glycoproteins G1 and G2. The L RNA encodes the L protein, which functions as the viral transcriptase/replicase. Within virions, the genomic RNAs of hantaviruses are thought to complex with the N protein to form helical nucleocapsids, the RNA component of which circularizes due to sequence complementarity between the 5' and 3' terminal sequences of each genomic segment.

Hantaviruses replicate exclusively in the host cell cytoplasm. Entry into host cells is thought to occur by attachment of virions to cellular receptors and subsequent endocytosis. Nucleocapsids are introduced into the cytoplasm by pH-dependent fusion of the virion with the endosomal membrane. Transcription of viral genes must be initiated by association of the L protein with the three nucleocapsid species. In addition to transcriptase and replicase functions, the viral L protein is also thought to have an endonuclease activity that cleaves cellular messenger RNAs (mRNAs) for the production of capped primers used to initiate transcription of viral mRNAs. As a result of this "cap snatching," the mRNAs of hantaviruses are capped and contain nontemplated 5' terminal extensions. The G1 (aka Gn) and G2 (Gc) glycoproteins form hetero-oligomers and are then transported from the endoplasmic reticulum to the Golgi complex, where glycosylation is completed. The L protein produces nascent genomes by replication via a positive-sense RNA intermediate. Hantavirus virions are believed to assemble by association of nucleocapsids with glycoproteins embedded in the membranes of the Golgi, followed by budding into the Golgi cisternae. Nascent virions are then transported in secretory vesicles to the plasma membrane and released by exocytosis.

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Respiratory failure from hantavirus pulmonary syndrome treated with high frequency oscillatory ventilation
From CHEST, 10/1/05 by Nauman A. Chaudary

INTRODUCTION: Hantavirus Pulmonary Syndrome (HPS) may lead to respiratory distress, hemodynamic compromise, and noncardiogenic pulmonary edema. High-Frequency Oscillatory Ventilation (HFOV) is an alternative mode of ventilatory support for patients with severe adult respiratory distress syndrome (ARDS). We present a severe case of HPS who did not respond to conventional ventilation. He was treated with HFOV, and recovered.

CASE PRESENTATION: A 41 year old man, presented with fever, headache, myalgias, dyspnea, and hematuria. He removed rodent droppings at a cabin in rural West Virginia two weeks earlier. He developed respiratory distress, and was intubated. Chest radiographs showed bilateral infiltrates (Figure 1). All cultures including bronchoalveolar lavage fluid were negative. Hantavirus-specific IgM and IgG antibodies were positive, and confirmed by the CDC. One day after intubation, PaO2 was 62 mmHg on pressure control ventilation (PCV), FIO2 1, and PEEP 14 cmH2O. Then, the ventilator was changed to HFOV, and oxygenation improved, but his blood pressure decreased, and he required fluids boluses, vasopressors, and a pulmonary artery catheter. The initial HFOV settings were mean airway pressure of 35 cmH2O, frequency 5 Hz, and amplitude 100 cmH2O. On subsequent days, he remained hypotensive and with low cardiac output. Pulmonary overdistension was suspected. HFOV was held for a few seconds, and a sudden improvement in hemodynamics was observed (table 1). Afterward, HFOV settings were adjusted. He developed multiple organ failure. CVVHD and anticoagulation were started. During the 2nd week in ICU, his PaCO2 level continued to rise (pH 7.13, and PaCO2 71 mmHg), and oxygen saturation dropped to 88% on FIO2 1. Pneumothorax was ruled out, and an emergent bronchoscopy was performed. A large amount of thick mucus obstructing lobar and segmental divisions in both lungs was observed and removed. This resulted in a sudden increase in oxygen saturation to 98%. At the end of the procedure pH was 7.21, PaCO2 51 mmHg, and PaO2 87 mmHg. After 10 days of HFOV, his clinical course improved slowly, and he was eventually discharged.

DISCUSSIONS: HPS carries a high mortality rate. In the USA, it is usually caused by the Sin Nombre virus. It was initially reported in the SW, but sporadic cases have also been observed in other states. It is transmitted by inhalation of contaminated aerosol from excreta of infected rodents. Our patient apparently acquired it while cleaning the cabin. After a three-week incubation period, patients usually present with fever, malaise, and myalgias. As in our patient, these symptoms may be followed by the common clinical characteristics of HPS: fever, thrombocytopenia, hemoconcentration, respiratory compromise, and ARDS. Positive Hantavirus-specific IgM or IgG antibodies confirm the diagnosis. Treatment of HPS includes intensive care support, and initiation of mechanical ventilation if needed. In ARDS, HFOV has been been shown to be safe and effective in improving oxygenation. To our knowledge, the use of HFOV in patients with HPS has not been reported. Barotrauma and hemodynamic compromise are complications of HFOV. The hemodynamic changes result from HFOV induced increase in intrathoracic pressure. In our case, holding of HFOV for a few seconds resulted in a sudden increase in blood pressure and cardiac output. In addition, mucus inspissation is another potential problem with HFOV. The presence of unexplained refractory hypercapnea, as occurred in our patient, should alert the physician for possible endotracheal tube or diffuse airway obstruction, and the need for bronchoscopy.

CONCLUSION: Intensive critical care support in patients with HPS may lead to a complete recovery. HFOV appeared to be effective in our patient. However, clinicians using this ventilator mode should be aware of the potential deterioration in hemodynamics, and possible diffuse intrapulmonary mucus plugging that HFOV can induce.

DISCLOSURE: Nauman Chaudary, None.

Nauman A. Chaudary MBBS * Melanie Fisher MD Luis Teba MD West Virginia University School of Medicine, Morgantown, WV

COPYRIGHT 2005 American College of Chest Physicians
COPYRIGHT 2005 Gale Group

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