RNA Viruses PDF

RNA Viruses - Single-Stranded RNA Viruses Group Members Presented Here Arenaviridae- Lassa virus Bunyaviridae- Sin nombre virus (SNV) Caliciviridae- Norovirus & Sapovirus Coronaviridae- Coronaviruses SARS Filoviridae Lake Victoria marburg virus, Ebola virus Flav...

RNA Viruses - Single-Stranded RNA Viruses Group Members Presented Here Arenaviridae- Lassa virus Bunyaviridae- Sin nombre virus (SNV) Caliciviridae- Norovirus & Sapovirus Coronaviridae- Coronaviruses SARS Filoviridae Lake Victoria marburg virus, Ebola virus Flaviviridae - Japanese encephalitis (JE) virus, - Dengue virus, - Yellow fever, - St. Louis encephalitis(SLE) virus, - West Nile virus (WNV), - Zika virus Orthomyxoviridae - Influenza A, - Influenza B , - Influenza C Paramyxoviridae - Parainfluenza viruses(PIVs) - Mumps virus - Measles virus - RSV Picornaviridae- Enteroviruses Retroviridae- HIV Rhabdoviridae- Lyssaviruses Togaviridae - Eastern Equine Encephalitis virus - Western EE virus - Venezuelan EE virus - Rubella virus Hepatitis viruses - HAV, HAB, HAC, HAD, HAE  Arenaviruses - Name is from the Latin arena, meaning “sand” - Under an electron microscope, virus appears sandy and granular. - Members of the arenaviruses are commonly divided into two groups: Old World and New World complexes. - Mode of transmission: Via contact with aerosolized virus or fomite contact with infected rodents Most well-known member: Lassa Virus Symptoms Most exposed individuals develop asymptomatic infection Some develop fever, headache, pharyngitis, myalgia, diarrhea, and vomiting Severe symptoms may occur. Pleural effusions, hypotension, and hemorrhaging Virus can cause meningitis. ➔ Transmission Community—acquired by contact with excretions of rodents ➔ Detection ELISA to detect IgM and IgG antibodies ➔ Treatment Ribavirin if started within 6 days of exposure Note: Arboviruses are viral infections spread by arthropod vectors. Bunyaviridae - Members of the group arboviruses Mode of transmission: Arthropod feeding on blood of vertebrate hosts including humans Symptoms: - Asymptomatic viremia develops after a few days. - While much less common, some hosts become febrile. - Most members can cause a febrile illness, hemorrhagic fever or encephalitis. Phlebovirus - Rift Valley fever virus (RVF) Encephalitis and hepatitis Targets brain and liver Bunyavirus - LaCrosse encephalitis virus (LAC) Aseptic encephalitis Targets brain California encephalitis virus Aseptic meningitis Targets brain Norovirus - Congo-Crimean hemorrhagic fever virus (CCHF) Hemorrhagic fever Targets vascular endothelium and liver High mortality Hantaan, Seoul, Puumala, and Dobra virus Korean War Hemorrhagic fever with renal syndrome (HFRS) Mostly Europe and Asia Exception: Seoul virus is worldwide  Bunyaviridae Sin Nombre Virus Also known as New World hantavirus Causative agent of hantavirus pulmonarysyndrome (HPS) Transmission: Inhalation of contaminated aerosolized infected rodent urine, saliva, and droppings Clinical manifestations : 3 to 5 febrile prodrome with fever, chills, and myalgia Clinical manifestations - After 3 to 5 day febrile prodrome, patients enter a phase of hypertensive shock and pulmonary edema. - Patient develops tachycardia, hypoxia, and hypotension. - Some patients develop DIC. Mortality rate is about 50%. Detection—EIAs to detect anti-SNV IgM and IgG antibodies, immunohistochemistry. Treatment is supportive. Noroviruses (NoVs) The most common cause of infectious gastroenteritis in the United States Populations at risk: Individuals in schools, colleges, nursing homes, and families and on cruise ships and in resort areas - Virus can be found in drinking water, swimming areas, and contaminated food. Transmission is most commonly foodborne. - Waterborne and person to person can be significant Symptoms - Severe nausea, vomiting, diarrhea, and low-grade fever - Infection rates as high as 50% - Illness usually subsides within 72 hours. Detection - Viruses cannot be grown in culture. - Electron microscopy or select reference laboratories perform serologic procedures. - RT-PCR - EIAs available but are not sensitive enough for diagnosing individuals suspected of being infected.  Sapovirus (SaVs) - Causes diarrhea and vomiting in infants, young children, and older patients ➔ Detection Electron microscopy Molecular methods (e.g., RT-PCR) Immunologic methods (e.g., ELISA) Coronaviridae - Also known as coronaviruses - Under electron microscopy, virus displays distinctive club-shaped projections on its surface. - Causes 15% of coldlike infections in adults - Higher seroconversion rates have been seen in children. Some pediatric diarrhea Targets the GI tract: Transmitted person to person by direct contact, droplet, or airborne routes. Also found in urine and feces - Coronaviruses are extremely fragile and difficult to culture. - Direct specimen testing by IF and EIA methods is possible. - Preferred detection method—RT-PCR - Infection that emerged in 2002 Severe acute respiratory syndrome coronavirus (SARS-CoV) Symptoms Requires hospitalization and intensive care Can be rapidly spread with close patient contact Filoviridae Marburg virus= Now Lake Victoria marburg virus Ebola virus: - Ebola-Sudan (EBO-S) - Ebola-Zaire (EBO-Z) - Ebola-Reston (EBO-R) - Ebola virus Tai Forest strain (formerly Ivory Coast) ➔ Lake Victoria Marburg Virus Symptoms of Lake Victoria marburg virus hemorrhagic fever - High fever 12 to 22 days - Maculopapular rash on trunk and extremities - Worsening nausea, vomiting, and diarrhea - Patients begin bleeding from the nose, gums, and GI tract. - Diffuse hemorrhaging, shock, multiple organ system involvement High mortality ➔ Transmission: Contact with infected monkeys or infected patients ➔ Detection - PCR  - Immunohistochemistry - IgM-capture ELISA ➔ Treatment - Primarily supportive and includes replacement of blood and clotting factors Ebola Virus ➔ Symptoms of Ebola virus hemorrhagic fever Fever, chills, myalgia, and anorexia—4 to 16 days after infection Sore throat, abdominal pain, diarrhea, vomiting,and bleeding from injection sites and the GI tract Hemorrhaging in the skin and internal organs may occur. ➔ Detection PCR, IF, or viral culture methods Electron microscopy of clinical samples will yield the characteristic virions. Flaviviridae - Japanese Encephalitis virus Ranges from influenza-like illness to encephalitis Emerging pathogen Dengue virus—causes two distinct diseases via mosquito bite Classic Dengue fever (DF): mild disease Fever, headache, myalgia, bone pain, and sometimes a rash Self-limiting, nonfatal Dengue hemorrhagic fever (DHF): severe disease Must be exposed to another strain of DF virus Classic DF with thrombocytopenia, hemorrhage, and shock; sometimes death Yellow Fever Virus - Causes yellow fever via mosquito bite Symptoms Asymptomatic Acute infection Fever, myalgia, backache, headache, anorexia, nausea, and vomiting Self-limiting, nonfatal, most recover Systemic toxic phase (15%) Fever, jaundice, hemorrhaging from mouth, eyes, nose, stomach, and other areas Kidney failure causing 50% mortality - Vaccine available Natural host: Monkeys Transmission - Aedes mosquitoes - Africa, South America, Caribbean Three difference transmission cycles Sylvatic- Maintained in monkey populations by mosquitoes Urban- Mosquito-infected person-mosquito-infected person Intermediate- Mosquito-monkey-mosquito-person-mosquito-monkey or person Saint Louis Encephalitis Symptoms - Usually asymptomatic - Fever only - Some develop meningoencephalitis Easier on children than adults Mortality 3% to 20% in symptomatic patients Natural hosts: Birds Transmission: Culex mosquitoes West Nile Virus Natural hosts: Birds Transmission: Mosquitoes Symptoms - Usually asymptomatic - West Nile fever if symptomatic Fever, headache, fatigue, occasional skin rash on the trunk, swollen lymph glands, and/or eye pain Some develop meningitis or encephalitis Adults over age 50 ➔ Detection IgG and IgM ELISA Rapid WNV ELISA Assay Indirect immunofluorescent assay to screen for antibodies RT-PCR, Taqman, and nucleic acid sequence- based amplification assays have been used for successful confirmatory identification. - No specific treatment - Hospitalization with supportive care when appropriate Zika Virus - Mosquito-transmitted disease that can also be transmitted via infected blood or sexual contact - Rarely mother to child - Endemic in areas of Africa and Asia - Significant number of cases reported across South, Central, and North Americas Symptoms: Fever, headache, fatigue, microcephaly in newborns ➔ Detection: FDA is looking to rapidly approve a PCR-based assay which will allow for more rapid testing for pregnant women which can be coupled with serology testing for both IgG and IgM antibodies to diagnose: Potential Zika virus exposure and/or infection  Influenza Viruses - The enveloped members can be distinguished using two major structural proteins. - Matrix (M) protein and nucleoprotein (NP) - Worldwide distribution - Originate as zoonotic infections Carried by different species of birds and mammals - Influenza season: Southern hemisphere—May to October Northern hemisphere—November to April Key to persistence of influenza virus is its antigenic variation. - Each year, antigenic drifts occur, caused by RNA replication of errors of the virus. - Antigenic variation drifts occur with all three types of influenza: A, B, and C. - When the surface antigens change drastically, an antigenic shift occurs resulting in a new antigen (known as H or N). Antigenic shift is only associated with influenza A. ➔ Influenza A Antigenic Shifts Influenza A - H1N1: 1918-1919 Spanish flu - H2N2: 1957-1958 Asian flu - H3N2: 1968 Hong Kong flu - H1N1 and H3N2 since 1977 - H5N1: 1998 Avian flu - H3N2v: 2011; mixture of avian, swine, and human viruses - H1N1 Swine flu: 2009 ➔ Symptoms - Flu: abrupt onset of headache, fever, chills, and dry cough - Later: high fever, myalgias, malaise, anorexia - Most cases are influenza A and B with higher levels of mortality. - Sometimes lead to secondary infections (bacterial pneumonia) - Spread by aerosols Influenza A and B Infects mammals and avian species Influenza C Causes mild upper respiratory illness in humans ➔ Specimen collection Nasopharyngeal swabs, washes, or aspiratescollected early in infection Flocked swabs are better at collecting epithelial cells. Do not freeze specimens. ➔ Testing DFA, EIA, optical immunoassays, cell lines Can culture in embryonated chicken eggs ➔ Treatment—only effective against influenza A - Neuraminidase inhibitors Zanamivir (Relenza) and oseltamivir (Tamiflu)  Parainfluenza Viruses Four types of PIVs can cause human disease, noted as PIV-1 through PIV-4. - Paramyxovirus: Parainfluenza 1 and 3 - Rubulavirus: Parainfluenza 2 and 4 ➔ PIV characteristics Enveloped helical RNA viruses Two distinct surface receptors HN: hemagglutinin-neuraminidase - Specificity of entry and attachment F: fusion antigen - Entry and spread respiratory disease in children Primary cause of respiratory disease in young children - Ages 2 to 4 years Parainfluenza 1 and 2 (PIV-1 and PIV-2) - Croup: laryngotracheobronchitis Ages less than 2 years - Parainfluenza 3 (PIV-3): Bronchiolitis Parainfluenza 4 (PIV-4): Mild upper respiratory infections ➔ Symptoms Rhinitis, pharyngitis, bronchiolitis, pneumonia ➔ Transmission by aerosolized droplets containing virus ➔ Specimen collection: Aspirates, secretions, and washes of the upper respiratory tract (URT) ➔ Detection - Hemadsorption, IF, EIA - Nucleic acid assay panels (for PIV-1 to PIV-3) Mumps Virus - Enveloped ssRNA virus: Possesses HN and F surface antigens ➔ Transmission - Droplets of infected saliva - Infects primarily children and adolescents Vaccination has greatly reduced incidence of mumps (MMR). Recent outbreak in lower Midwest, 2006 ➔ Causative agent of infectious parotitis - Swollen parotid glands - May include swelling of testes, ovaries, and pancreas - Can cause permanent sterility - Rare cases of meningitis reported ➔ Specimen collection Swabs of the Stensen duct or saliva Collected from 9 days before until 8 days after parotitis appears - Urine specimens ➔ Detection - Hemadsorption inhibition, hemagglutination inhibition, IF, EIA - Serology: fourfold rise in antibodies from paired sera  Measles Virus - Belongs to the genus Morbillivirus - Also known as rubeola Part of the MMR vaccine Highly contagious Spreads by aerosol - Initial viral replication takes place in the mucosal cells of the respiratory tract. Then replicates in the local lymph nodes and spreads systematically Incubation period is 7 to 10 days. ➔ Symptoms - Abrupt onset Sneezing, runny nose, red eyes, and rapid rising fever - 2 to 3 days later, maculopapular rash with fever On head and trunk Whitish spots (Koplik’s spots) with red background - Complications: otitis, pneumonia, encephalitis - Resolution of symptoms provides lifelong immunity. ➔ Specimens of choice Nasopharynx and urine Virus can only be recovered during early stages of infection. ➔ Detection Easily diagnosed clinically Few requests for laboratory identification are made. Cell culture, serum neutralization, EIA, IF, serologic tests, nucleic acid testing when indicated Respiratory Syncytial Virus - Member of the genus Pneumovirus A causative agent of: - Croup, bronchitis, bronchiolitis, interstitial pneumonia Most common cause of lower respiratory tract disease among infants and young children worldwide Nosocomial infections in hospitals and clinics Can cause morbidity and mortality in older adult patients RSV does not confer complete immunity - Multiple infections can occur throughout life and can besevere in older adults. the immunocompromised. those with cardiac and respiratory problems. ➔ Symptoms Bronchitis, bronchiolitis, interstitial pneumonia Carriers can be asymptomatic and have RSV in nares. Transmission by large particle droplets and fomites ➔ Specimen collection Nasopharyngeal swabs and washes ➔ Detection Directly from specimen—DFA, EIA Cell culture followed by IF, EIA, serum neutralization tests Rapid antigen kits PCR ➔ Treatment No gold standard, controversy exists among possible treatments Human Metapneumovirus (hMPV) - Similar to infections caused by RSV, influenza virus, and PIV in that symptoms grow very slowly in standard viral cultures - Clinical disease varies from mild URT to acute lower respiratory infection. - Fever, nonproductive cough, sore throat, wheezing, congestion, shortness of breath, lethargy ➔ Specimen of Choice Swabs collected from the nostrils, placed in transport media, and transported on ice to the laboratory ➔ Detection Cell culture Molecular analysis RT-PCR, fluorescent monoclonal antibodies Picornaviridae - Small naked viruses - Causes various conditions including Enteroviruses Members of the genus Enterovirus - Enteroviruses 73 to 120 Hepatitis E virus (HEV) A, HEV B, HEV C, HEV D - Rhinovirus A to C - Polioviruses 1 to 3 - Coxsackieviruses A1 to A24 - Coxsackieviruses B1 to B6 - Echoviruses 1 to 33 More prevalent in areas with poverty, overcrowding, poor hygiene, and poor sanitation ➔ Modes of transmission - Aerosol inhalation, fecal–oral, and fomites Port of entry is alimentary canal via the mouth.  - Viruses replicate in lymphoid tissue of pharynxand gut. May result in viremia and virus spread to spinal cord, heart, or skin ➔ Specimens of choice Collect early in course of infection whenever possible Pharynx (before onset of symptoms and for 1 to 2 weeks afterward best) Throat Feces (for up to 6 weeks afterward) Rectum CSF Conjunctiva Enteroviruses Polioviruses - Infect the nervous system and can cause paralysis Temporary intestinal damage Neurons are not replaced= Results in death and permanent paralysis Several vaccines available - Produces antibodies that protect against invasion of the meninges, thus preventing CNS involvement and poliomyelitis Enteroviruses Coxsakievirus A Hand, foot, and mouth disease (HFMD) Primarily types A5, A10, and A16 Naked ssRNA viruses ➔ Transmission by fecal–oral route or fomites ➔ Symptoms Malaise, headache, abdominal pain Small painful sores on tongue, buccal mucosa, and soft palate Maculopapular rash on hands, feet, and buttocks Bullae on hands and feet Swabs of mouth and bullae can detect virus. Rhinoviruses - Small naked ssRNA viruses Resistant to detergents and lipid solvents pH sensitive below 6 More than 100 serotypes exist ➔ Transmission Aerosol droplets, fomites ➔ Causative agent of the common cold Nasal congestion, runny nose, sneezing, headache, sore throat, cough, sometimes bronchitis, rarely fever Generally increased incidence during winter and spring Retroviridae Members of this group, known as retroviruses, have a unique mode of replication. - They require an RNA-dependent DNA polymerase (reverse transcriptase) to synthesize DNA from the RNA genome. - These viruses are not cytolytic but are associated with several leukemias, sarcomas, and lymphomas.  Retroviruses Classification - Oncovirinae Human T-lymphotropic virus 1, 2, 5 (HTLV-1, HTLV-2, HTLV- 5) Cause leukemias, sarcomas, and lymphomas - Lentivirinae Human immunodeficiency virus 1 (HIV-1) HIV-2 HIV Spherical virus with a three-layer structure - Enveloped ssRNA - In center of virus Two identical copies of ssRNA and reverse transcriptase surrounded by an icosahedral capsid - Nucleocapsid Enclosed by matrix shell to which an envelope of the host cell origin is attached - Inserted into viral envelope Viral glycoprotein (gp) trimmers or spikes Diagnostically important structural proteins - P24, gp41, gp120, gp160 ➔ Transmission Blood or exchange of body fluids (sexual contact) or congenital infection Not transmitted by sweat, saliva, tears, urine, milk - New cases in 2011 Associated with: Heterosexual contact: 24% Men who have sex with men: 66% Intravenous (IV)-drug use: 6% Heterosexual contact and IV-drug use: 3% Transfusions of mother to infant: 1% - Once HIV enters the body, primary target cells CD4+ T cells Monocytes Macrophages - Acute infections generally mild and can resemble infectious mononucleosis - Patient will enter clinical latency.Virus in the background rapidly replicating in lymphoid tissue - Virus destroys T-helper cells that are critical in the immune response to infectious agents. Patient begins experiencing several chronic and recurrent infections. With time, opportunistic infections become more severe. Patient can also develop virus-induced cancers. Kaposi sarcoma Death usually occurs from the resulting opportunistic infections. ➔ Clinical manifestations CNS involvement, often seen in HIV-associated dementia complex, as well as other neurologic problems - Opportunistic infections - Tumors - Kaposi sarcoma May cause painful swelling and painful May involve liver, lungs, digestive tract ➔ Detection Generally based on the demonstration of anti-HIV antibodies and in some cases, detection of viral antigens and RNA EIA, IF - Rapid screening assays using serum, plasma, saliva Western blot Confirmatory test Positive: ≥2 bands p24, gp41, and gp120/160 Indeterminate: one band or other bands not listed above - p66, p51, p31, p17, or others Negative: absence of any bands EIAs and other tests are preliminary Cross-reactivity Retest positive EIA in duplicate Require confirmation - Treatment Cocktails of these drugs  HAART: highly active antiretroviral therapy - Very expensive - Hard to implement in poor or developing countries Viral load monitoring - PCR-based testing to assess copy number Lyssaviruses - Several viral strains that belong to the genus Lyssavirus cause rabies - Endemic in most areas of the United States Very diffuse animal pathogen that can infect humans Raccoons, skunks, bats, foxes, cats, dogs, cattle, and coyotes ➔ Diagnosis Find animal and examine brain tissue ➔ Transmission Bites or scratches from infected animals ➔ Symptoms Pain in exposure site Vague flulike symptoms and personality changes Late stage CNS changes involving hallucinations, paralysis, excessive salivation, hydrophobia, bouts of terror, seizures, respiratory and cardiac problems; leads to coma and death ➔ Treatment Must occur prior to symptoms Postexposure prophylaxis is 100% effective. Cleaning wound, rabies Ig, vaccination Vaccines for professionals at high risk Togaviridae Members in the family Togaviridae - Alphavirus Eastern equine encephalitis (EEE) Western equine encephalitis (WEE) Venezuelan equine encephalitis (VEE) - Rubivirus Rubella virus - Arterivirus No human cases ➔ EEE Symptoms Range of effects from Influenza-like illness to encephalitis Mortality rate of about 40% of cases Of those who survive, almost 50% suffer permanent CNS damage. Natural reservoir of the virus: Birds - Spread to humans and horses via mosquito bite  ➔ WEE Symptoms Sometimes asymptomatic Mild infection Fever, headache, nausea, mental status changes Develop encephalitis 30% of infected children and infants suffer permanent CNS damage. Mortality, 3% ➔ VEE Symptoms - Infected adults often develop an influenza-like illness. - Infected children typically develop encephalitis. Mortality is much less common than individuals with EEE or WEE. Rubella Virus Causative agent of German measles Mild febrile illness - Symptoms Erythematous, maculopapular rash starting on the face and moving down trunk and limbs No rash on palms and soles Transient arthritis may occur in children and adults. Transplacental transmission to fetus - Can result in birth defects, fetal death, cataracts in fetus, and spontaneous abortion (congenital rubella syndrome) ➔ Transmission occurs via droplets ➔ Specimens of choice - Nasopharyngeal specimen - Any secretion or tissue ➔ Detection - Serologic assays, molecular tests under evaluation, PCR in clinical research trials ➔ Prevention Effective attenuated vaccine should be administered to all children and young women before they become sexually active.  HAV - Enteric virus Small icosahedral, naked ssRNA virus ➔ Transmission Fecal–oral route via close personal contact or contaminated food - Infects people of all ages Highest infection rate in children between age 5 and 14 ➔ Symptoms Incubation is approximately 1 month. - Transient viremia Virus reaches liver and replicates in hepatocytes. Virus passes into the intestine; viral shedding begins and can last for months. - In children younger than 5 years Mild to severe prolonged, self-limiting hepatitis - Fever, chills, fatigue, malaise, aches, pains, and sometimes jaundice ➔ Risk factors Sexual or household contact with an infected person Daycare contacts Foodborne or waterborne outbreaks IV drug use International travel ➔ Detection Serology: HAV IgM antibody RT-PCR is now being used - Safe, effective vaccines are available. HBV - Enveloped, partially dsDNA virus - Chronic hepatitis; bloodborne pathogen ➔ Routes of transmission Sexual Perinatal Parenteral - High risk groups IV-drug users Men who have sex with men (MSM) Individuals from endemic areas Household contacts of those with HBV Tattoos and piercings Health care personnel Infants born to HBV-positive mothers - Vaccine is available. ➔ Symptoms Infects liver cells, which undergo immune-mediated destruction causing Fever, anorexia, hepatic tenderness, sometimes jaundice, elevated serum aminotransferase levels - Ninety percent resolve the infection without serious sequelae. Ten percent become chronic carriers. High risk for cirrhosis, hepatic carcinoma HDV - Delta hepatitis Defective virus that requires HBV for replication Requires HBsAg as its envelope ➔ Transmission Blood and blood products Sexual contact ➔ Risk factors IV-drug users Limited numbers of MSM in certain locations ➔ Infection Coinfection: infection with HBV and HDV at the same time Greater likelihood of a more severe acute infection progressing to fulminant hepatitis - Superinfection: infection in chronic HBV carrier Chronic HDV, which increases the likelihood of cirrhosis ➔ Detection Serology: anti-HDV PCR: HDV, RT-PCR: HDV RNA  HCV Bloodborne pathogen ➔ Transmission Blood and blood products Sexual contact ➔ Risk factors Blood exposure, usually transfusions Sometimes sexual contact IV-drug use ➔ Symptoms May be subtle and take time to become apparent Acute hepatitis less severe than HBV Chronic in 50% of infected patients Twenty percent of chronic carriers develop cirrhosis within 20 to 30 years. Cirrhosis increases the likelihood of liver cancer. - HVC has the highest mortality rate. - Among HAV, HBV, and HCV ➔ Detection Gene amplification tests prove that HCV RNA appears in newly infected patients in as little as 2 weeks. - Most detection is via serologic testing. Anti-HCV antibodies - Does not produce lifelong antibodies - Persistence indicates chronic infection ➔ Detection Enzyme-linked immunosorbent assay (ELISA) screening test c100 or 5-1-1, c33, c22 Recombinant immunoblot assay (RIBA) (Western blot) No bands present: negative One band (c100, 5-1-1 count as one): indeterminate Two or more bands present: positive HEV Small, naked ssRNA virus Waterborne enteric agent, transmitted via fecal–oral route - Fecal contamination of drinking water Causes acute, self-limiting disease, similar to HAV - Found in developing countries Asia, Africa, and Central America No U.S. sources ➔ Symptoms Acute, self-limiting disease Fever, malaise, nausea, vomiting, jaundice, and dark urine Mortality is 1% to 3%, with greater mortality of 15% to 20% in pregnant women. ➔ Detection An ELISA test has been developed to detect IgG and IgM antibodies to HEV but is not currently performed in diagnostic laboratories in the United States. Other Hepatitis Viruses HGV Not common in United States Clinical significance is still under investigation. SEN Bloodborne Circular DNA genome Possible link to hepatitis; not definitively linked to any human disease Appears to be linked to blood transfusions TTV - May be associated with posttransfusion hepatitis