Hantavirus Pulmonary Syndrome Cheat Sheet

Hantavirus Pulmonary Syndrome (HPS) 1. Hantavirus pulmonary syndrome (HPS), caused by a previously unknown hantavirus, was first recognized in May 1993. The disease begins with nonspecific symptoms that can include fever, muscle aches, headache, abdominal pain, nausea, and vomiting, followed later by coughing and shortness of breath. The symptoms usually occur between 1 and 6 weeks after exposure to virus­laden rodent excreta. The disease rapidly progresses to cardiac and respiratory failure, requiring that the patient receive intensive care. Family Bunyaviridae 5 genera, 250 species Genus Human disease Bunyavirus LaCrosse encephalitis, others Phlebovirus Rift Valley fever, sandfly fever Nairovirus Crimean­ Congo hemorrhagic fever Crimean­Congo Tospovirus Plant virus, no known human disease Hantavirus Hemorrhagic fever with renal syndrome Hantavirus pulmonary syndrome 2. Family Bunyaviridae: Hantaviruses are members of the family Bunyaviridae, which consists of 5 genera and 250 species. Hantaviruses can cause hantavirus pulmonary syndrome (HPS) or hemorrhagic fever with renal syndrome (HFRS). The 5 genera of Bunyaviridae include Bunyavirus, Phlebovirus, Nairovirus, Tospovirus, and Hantavirus. Characteristics of Hantaviruses • No arthropod vector established Unique among genera of Bunyaviridae • Rodent hosts Genus and possibly species specific • Transmission Aerosolization of rodent excreta 3. Characteristics of Hantaviruses: Hantaviruses are unique among Bunyaviridae genera in that they are not associated with an arthropod vector. In general, a distinct rodent species is the reservoir for each hantavirus. Transmission of hantaviruses to humans most often occurs via inhalation of aerosolized, virus­ laden rodent excreta. Transmission of Hantaviruses Chronically infected rodent Horizontal transmission of infection by intraspecific aggressive behavior Virus is present in aerosolized excreta, particularly urine Virus also present in throat swab and feces Secondary aerosols, mucous membrane contact, and skin breaches are also sources of infection 4. Transmission of Hantaviruses: The virus is horizontally transmitted between rodents through intraspecific aggressive behaviors, such as biting. The virus is transmitted to humans from aerosolized rodent excreta, particularly urine. Transmission to humans also can occur from inhalation of secondary aerosols, and from rodent bites or other direct contact of infectious material with mucous membranes or broken skin. Phylogeny of Hantaviruses: Based on Sequence of S Segment (Subfamily, Hantavirus, Location, Host) S HTN Korea Apodemus agrarius DOB Slovenia Apodemus flavicollis SEO Japan Rattus norvegicus MURINAE ARVICOLINAE SIGMODONTINAE PUU Finland Clethrionomys glareolus PUU Russia Clethrionomys glareolus PUU Sweden Clethrionomys glareolus PUU Belgium Clethrionomys glareolus TOP Russia Lemmus sibiricus KBR Russia Microtus fortis TUL Russia Microtus arvalis TUL Czech Microtus arvalis TUL Slovakia Microtus arvalis PH New York Microtus pennsylvanicus PH Maryland Microtus pennsylvanicus ISLA California Microtus californicus MULE Southern US Sigmodon hispidus (texianus) BCC Florida Sigmodon hispidus BAY Southeastern US Oryzomys palustris ANDES Argentina & Chile Oligoryzomys longicaudatus LEC Argentina Oligoryzomys flavescens RIOM Bolivia & Peru Oligoryzomys microtis LN Paraguay & Bolivia Calomys laucha SN New Mexico Peromyscus maniculatus SN California Peromyscus maniculatus NY New York Peromyscus leucopus NY Rhode Island Peromyscus leucopus MON West Virginia Peromyscus maniculatus ELMC Western US & Mexico Reithrodontomys megalotis RIOS Costa Rica Reithrodontomys mexicanus 5. Phylogeny of Hantaviruses, Based on the Sequence of the S Segment (one of three genomic RNA segments): This phylogenetic tree depicts the relationship among the viruses, the primary rodent reservoir of the virus, and the geographic origin of the characterized virus. Phylogeny of Hantaviruses: Based on Sequence of M Segment (Subfamily, Hantavirus, Location, Host) HTN Korea Apodemus agrarius HTN China Apodemus agrarius SEO Japan Rattus norvegicus SEO Korea Rattus norvegicus SEO China Rattus norvegicus THAI Thailand Bandicotta indica DOB Slovenia Apodemus flavicollis PUU Sweden Clethrionomys glareolus MURINAE PUU Russia Clethrionomys glareolus ARVICOLINAE PUU Finland Clethrionomys glareolus PUU Belgium Clethrionomys glareolus TUL Czech Microtus arvalis PH Maryland Microtus pennsylvanicus SIGMODONTINAE BCC Florida Sigmodon hispidus BAY Southeastern US Oryzomys palustris Hu39694 Argentina unknown LEC Argentina Oligoryzomys flavescens ORN Argentina Oligoryzomys longicaudatus LN Paraguay & Bolivia Calomys laucha SN California Peromyscus maniculatus SN New Mexico Peromyscus maniculatus M NY Rhode Island Peromyscus leucopus NY New York Peromyscus leucopus BR Oklahoma Peromyscus leucopus BR Indiana Peromyscus leucopus ELMC Western US & Mexico Reithrodontomys megalotis 6. Phylogeny of Hantaviruses, Based on the Sequence of the M Segment (one of three genomic RNA segments): This phylogenetic tree depicts the relationship among the viruses, the primary rodent reservoir of the virus, and the geographic origin of the characterized virus. Hantaviruses in the Old World Subfamily Murinae associated viruses Virus Host Location Hantaan Dobrava Apodemus agrarius Apodemus flavicollis Apodemus agrarius Rattus norvegicus Rattus rattus Asia, Far East Russia HFRS Balkans HFRS Europe Worldwide HFRS Seoul Disease Subfamily Arvicolinae associated viruses Virus Host Location Puumala Clethrionomys glareolus Europe Disease HFRS Numerous other hantaviruses have been identified but not linked to human disease 7. Hantaviruses in the Old World: At least four Old World hantaviruses ­­ Hantaan, Dobrava, Seoul, and Puumala viruses ­­ can cause hemorrhagic fever with renal syndrome (HFRS) and are endemic in parts of Europe and Asia. Murine rodents carry Hantaan, Dobrava, and Seoul viruses. An Arvicoline rodent species carries Puumala virus, which causes a milder form of HFRS. Numerous other Old World hantaviruses have been identified but have not been linked to human disease. Hantaviruses in the New World (1) Subfamily Sigmodontinae associated viruses Host Location Disease Peromyscus maniculatus West & Central HPS U.S. & Canada Monongahela Peromyscus maniculatus Eastern U.S. & HPS Canada New York Peromyscus leucopus Eastern U.S. HPS Bayou Oryzomys palustris Southeastern U.S. HPS Black Creek Canal Sigmodon hispidus Florida HPS Virus Sin Nombre Numerous other hantaviruses have been identified but not linked linked to human disease 8. Hantaviruses in the New World ­­ North America: Hantaviruses in the New World are associated with hantavirus pulmonary syndrome (HPS). Sigmodontine rodents carry the hantaviruses that cause HPS and are found throughout the Americas. Sin Nombre virus, carried by Peromyscus maniculatus, is the predominant cause of HPS in the United States and Canada. Mononghela, New York, Bayou, and Black Creek Canal viruses also cause HPS and are found in eastern Canada and eastern and southeastern United States. Numerous other hantaviruses have been identified but have not been linked to human disease. Hantaviruses in the New World (2) Subfamily Sigmodontinae associated viruses (cont.) Virus Host Location Andes Oligoryzomys longicaudatus Argentina & Chile Oligorozomys longicaudatus Oligoryzomys flavescens Unknown Northwestern Argentina Central Argentina Central Argentina Oran Lechiguanas Hu39694 Laguna Negra Calomys laucha Bermejo Oligoryzomys chacoensis Juquitiba Choclo Unknown Oligoryzomys fulvescens Paraguay & Bolivia Northwestern Argentina Brazil Panama Disease HPS HPS HPS HPS HPS Numerous other hantaviruses have been identified but not linked to human disease 9. Hantaviruses in the New World ­ South and Central America: In South and Central America, hantaviruses that have been identified as causing HPS are Andes virus in Argentina and Chile; Andes­like viruses including Oran, Lechiguanas, and Hu39694 in Argentina; Laguna Negra virus in Bolivia and Paraguay; Bermejo virus in Argentina; Juquitiba virus in Brazil; and Choclo virus in Panama. Numerous other hantaviruses have been identified but have not been linked to human disease. New World Hantaviruses New York Sin Nombre Peromyscus leucopus Peromyscus maniculatus Prospect Hill Microtus pennsylvanicus Muleshoe Sigmodon hispidus Bloodland Lake Microtus ochrogaster Isla Vista Bayou Microtus californicus Oryzomys palustris Black Creek Canal El Moro Canyon Sigmodon hispidus Reithrodontomys megalotis Rio Segundo Reithrodontomys mexicanus Calabazo Juquitiba Zygodontomys brevicauda Ca ño o Delgadito Cañ Choclo Sigmodon alstoni Oligoryzomys fulvescens Rio Mamore Oligoryzomys microtis Orá n Orán Oligoryzomys longicaudatus Bermejo Oligoryzomys chacoensis Andes Oligoryzomys longicaudatus Unknown Host Laguna Negra Calomys laucha Maciel Necromys benefactus Hu39694 Unknown Host Lechiguanas Oligoryzomys flavescens Pergamino Akodon azarae 10. A map of Western Hemisphere shows the distribution of New World hantaviruses and their associated rodent hosts. The viruses in bold print cause disease in humans including: Sin Nombre, Choclo, Orán, Andes, New York, Bayou, Black Creek Canal, Juquitiba, Laguna Negra, Hu39694, and Lechiguanas. Virus (Rodent Host) Sin Nombre (Peromyscus maniculatus) Muleshoe (Sigmodon hispidus) Isla Vista (Microtus californicus) El Moro Canyon (Reithrodontomys megalotis) Calabazo (Zygodontomys brevicauda) Choclo (Oligoryzomys fulvescens) Caño Delgadito (Sigmodon alstoni) Rio Mamore (Oligoryzomys microtis) Orán (Oligoryzomys longicaudatus) Bermejo (Oligoryzomys chacoensis) Andes (Oligoryzomys longicaudatus) New York (Peromyscus leupous) Prospect Hill (Microtus pennsylcanicus) Bloodland Lake (Microtus ochrogaster) Bayou (Oryzomys palustris) Black Creek Canal (Sigmodon hispidus) Rio Segundo (Reithrodontomys mexicanus) Juquitiba (Unknown host) Laguna Negra (Calomys laucha) Maciel (Necromys benefactus) Hu39694 (Unknown host) Lechiguanas (Oligoryzomys flavescens) Canada (36)3 Countries with reported cases of HPS (no of cases) Hantavirus Pulmonary Syndrome Number of cases by date 1PAHO United States (335)7 5 01 2January 02 3May 02 4August 02 September 02 6 October 02 7 November 02 Countries with no reported cases of HPS Panama (31) 6 Bolivia (20)4 Chile (273)5 Brazil (168)2 Paraguay (74)1 Uruguay (23) 1 Argentina (404)4 11. A map of Western Hemisphere shows the number of cases of Hantavirus Pulmonary Syndrome in the respective country. Country (Number of Cases) Argentina (404) Brazil (168) Bolivia (20) Canada (36) Chile (273) Panama (31) Paraguay (74) United States (335) Uruguay (23) Peromyscus maniculatus Deer mouse Sigmodon hispidus Cotton rat 12. Deer Mouse (Peromyscus maniculatus) and Cotton Rat (Sigmodon hispidus): The deer mouse is the primary rodent host for Sin Nombre virus, the main etiologic agent of HPS in North America. The cotton rat is the primary rodent host for the Black Creek Canal virus. Infected rodents show no visible evidence of acute or chronic infection. Sin Nombre Virus Characteristics Family Bunyaviridae Transmission vertebrate hosts, no arthropod vectors Viral particles spherical, 80­ 120 nm 80­120 Structural proteins Glycoproteins: G1, G2 nucleoprotein: N Genome ss­ RNA, trisegmented, ss­RNA, trisegmented, negative polarity 13. Characteristics of Sin Nombre Virus: Sin Nombre virus belongs to the family Bunyaviradae and contains three genomic RNA segments of negative polarity. The virion of Sin Nombre virus is spherical and is 80­120nm in diameter. The virion contains two glycoproteins, G1 and G2, located on the outer surface, which are the nucleoprotein and the viral polymerase. Hantavirus Pulmonary Syndrome Clinical Presentation Most Frequent Fever Myalgia Nausea/Vomiting Cough Other Dizziness Arthralgia Shortness of Breath (late in Rare Rhinorrhea Sore Throat the course of disease) 14. Clinical Presentation of HPS: Most frequent symptoms include fever, myalgia, nausea/vomiting, and cough. Other symptoms include dizziness, arthralgia, and shortness of breath. Rhinorrhea and sore throat are rarely seen. Hantavirus Pulmonary Syndrome Physical Examination • Tachypnea • Tachycardia • Hypotension • Crackles or rales on lung examination 15. Physical Examination Findings of HPS: Typical findings include fever, tachypnea, tachycardia, hypotension, and crackles or rales on lung examination. Hantavirus Pulmonary Syndrome Radiographic Findings • Bilateral interstitial infiltrates ­ moderate to rapid progression • Bilateral alveolar infiltrates • Pleural effusion 16. Radiographic Findings of HPS: Findings usually include interstitial edema, Kerley B lines, hilar indistinctness and peribronchial cuffing with normal cardiothoracic ratios. HPS begins with minimal changes of interstitial pulmonary edema and rapidly progressing to alveolar edema with severe bilateral involvement. Pleural effusions are common and are often large enough to be evident radiographically. Radiographic Progression of HPS in the Lungs May 27, 1993 May 30, 1993 May 31, 1993 17. Radiographic Progression of HPS in the Lungs: These chest X­rays of an HPS patient were taken on May 27, May 30, and May 31, 1993. Approximately one­third of patients show evidence of pulmonary edema in the initial radiograph. Forty­ eight hours after the initial radiograph, virtually all patients demonstrate interstitial edema and two­thirds have developed extensive bibasilar or perihilar airspace disease (courtesy of L. Ketai). Hantavirus Pulmonary Syndrome Common Laboratory Findings Hematology Low platelet count Atypical lymphocytes (immunoblasts (immunoblasts)) Left shift on WBC differential Elevated hematocrit Elevated WBC Chemistry Low albumin Elevated LDH Elevated AST (SGOT) Elevated ALT (SGPT) 18. Common Laboratory Findings: Notable hematological findings include low platelet count, immunoblasts, left shift on WBC differential, elevated WBC, and elevated hematocrit. The large atypical lymphocyte shown here is an example of one of the laboratory findings that, when combined with a bandemia and dropping platelet count, are characteristic of HPS. Notable blood chemistry findings include low albumin, elevated lactate dehydrogenase (LDH), elevated aspartate aminotransferase (AST or SGOT) and elevated alanine aminotransferase (ALT or SGPT). Clinical Progression of HPS Prodrome Cardiorespiratory Convalescence Fever Pulmonary edema Shock Diuresis Immunoblasts Platelets HCT AST LDH ++ ++ + + + 3­ 6 days 3­6 ++ + + ++++ + + +++ ++ + + + +++++++ + + ++++++ 7­ 10 days 7­10 19. Clinical Course of HPS: Clinical course of HPS starts with a febrile prodrome that may ultimately lead to hypotension and end­organ failure. The onset of the immune response precedes severe organ failure, which is thought to be immunopathologic in nature. Hypotension does not result in shock until the onset of respiratory failure, but this may reflect the severe physiologic impact of lung edema. HPS Management • Early aggressive intensive care • Early use of inotropic agents (Dobutamine) • Early ventilation • Careful monitoring – Oxygenation – Fluid balance – Blood pressure 20. HPS Patient Management: Treatment of patients remains supportive in nature. Early aggressive intensive care is imperative, and may include early use of inotropic agents, such as dobutamine, to augment myocardial contractivity. Patients require early ventilation and careful monitoring of oxygenation, fluid balance, and blood pressure. ICU Monitoring and Therapy • Early use of inotropic agents • Mechanical ventilation • Judicious volume resuscitation • Early PA catheter 21. ICU Monitoring and Therapy: Because of the rapid progression of the disease, patients should be quickly transferred to a fully equipped emergency facility when necessary. Patients should be closely and continually monitored by a physician so that life­supporting procedures can be performed. Inotropic agents, mechanical ventilation, early PA catheterization and judicious volume resuscitation are elements of supportive care.