Biomed RNA Viruses 2024 PDF

Major RNA Viruses January 21, 2025 Shafik Habal, MD...

Major RNA Viruses January 21, 2025 Shafik Habal, MD Professor, Medical Microbiology and Immunology Philadelphia College of Osteopathic Medicine Georgia Campus Certain materials are included under the fair use exemption of the U.S. Copyright Law and have been prepared according to the fair use guidelines and are restricted from further use. Learning Objectives 1. Classify the DNA viruses according to structure & genome (i.e. single stranded vs double stranded) 2. Discuss the importance of latency to clinical disease 3. For the following viruses (Herpesviruses, adenoviruses, papillomaviruses, polyomavirus, parvoviruses, hepatitis B virus & poxviruses) describe: 1. source & transmission 2. timeline of infection within the infected host 3. disease associations & clinical manifestations 4. diagnosis, management & prevention (if discussed) Reading assignment: Murray’s Medical Microbiology, 9th edition Chapters: 46, 47, 48, 49, 50 (pages 500-502), 51, 52, and 53  Viral Structure Capsid symmetry: Icosahedral Helical Composed of identical proteins “capsomeres” Classified based on their structure “Icosahedral” or “Helical” Protects the genetic material Recognition and attachment to host  Viral Classification Baltimore Classification based on mRNA synthesis Positive sense RNA viruses act as mRNA (act as host mRNA) 🡪 They can be translated directly 🡪 Proteins Negative sense RNA viruses carry their own RNA-dependent-RNA-polymerase to make positive sense copy. Therefore, they require transcription followed by translation  RNA VIRUSES +ssRNA -ssRNA dsRNA Enveloped Nonenveloped Enveloped Nonenveloped Icosahedral Helical Icosahedral Helical Icosahedral Reoviridae Coronaviridae Orthomyxoviridae Flaviviridae Picornvaviridae Paramyxoviridae Togaviridae Caliciviridae Rhabdoviridae Retroviridae Herpesviridae Filoviridae Bunyaviridae Arenaviridae  General information about RNA viruses All RNA viruses replicate in the cytoplasm except: Orthomyxoviridae (Influenza) and Retroviridae All RNA viruses are single – stranded except: Reoviridae (Rotavirus) All RNA viruses are enveloped except: Picoranaviridae, Caliciviviridae, Hepeviridae (Hep E), and Reoviridae All –ssRNA viruses are helicial High rate of mutation Small genome PICORNAVIRIDAE RNA VIRUSES +ssRNA -ssRNA dsRNA Include some of the smallest viruses Naked 🡪 Resistant to ether, chloroform, and alcohol Enveloped Nonenveloped Nonenveloped Enveloped Reoviridae Flavirividae Picornaviridae Picornaviridae Orthomyxoviridae Togaviridae Calicivridiae Paramyxoviridae Retroviridae Rhabdoviridae Coronaviridae Herpesviridae Filoviridae Bunyaviridae Arenaviridae  Classification of Picornaviruses Family Genus Subtypes Picornaviridae Enterovirus Poliovirus 1 – 3 Coxsackie A 1 – 24 Coxsackie B 1 – 6 Enterovirus 68 – 71 Echo 1 – 34 Rhinovirus Human Rhinovirus 1 – 115 (not stable under acidic condition) Hepatovirus Hepatitis A virus  Poliovirus The virus was first identified in 1909 and cell cultured in 1949 There are 3 serotypes with only 33-66% homology (no identical antigens) Humans are considered the only “known” susceptible host Worldwide distribution (before the availability of a vaccine) Described in 1890 1st Epidemic 1940s Salk inactivated vaccine ancient times 1840 1st medical report 1909 Identification 1958 Sabin oral vaccine Global wild and vaccine-derived cases of polio, 2000-2022 The dream of wiping out polio might need a rethink https://extranet.who.int/polis/public/CaseCount.aspx  Since 1988, wild polio cases declined by 99.9% Type 2 eradicated in 2015 and type 3 eradicated as of 2018 The last evidence of polio type 1 transmission in Nigeria was in 2018 leaving only two polio endemic countries: Pakistan and Afghanistan. Eradication efforts stopped 14/29 circulating vaccine derived outbreaks in 2019 (usually in low polio immunity settings) https://www.cdc.gov/polio/progress/index.htm  Poliovirus IPV Almost 70 – 90% of infections are type – 1 Last case in the US: 1979 Last reported native case OPV Last case in the western hemisphere: 1994 On the road to global eradication  Pathogenesis of Poliovirus Transmission: Predominantly fecal – oral (ingestion) Infects and replicates in cells of the oropharyngeal an intestinal mucosa Invades and replicates in local lymph nodes and GALT Primary (transient) viremia - 95% of cases Secondary viremia (spread to other organs) – 5% In about 1% of the cases, it crosses the blood brain barrier to the CNS Virus is shed in feces  Clinical Manifestation of Poliovirus Infection 90 – 95% of the cases remain subclinical 🡪 Asymptomatic 5 – 8% of the cases may be associated with flu-like symptoms, sore throat, etc. 1 – 2% of the cases are associated with major clinical manifestation – CNS – Meningitis (aseptic) – Encephalitis – Paralytic poliomyelitis  Paralytic Poliomyelitis Symptoms vary depending on the affected tissue Involvement of the cells of the anterior horn results in “flaccid paralysis” Involvement of the medulla may result in paralysis of the diaphragm 🡪 Death There are 3 types of paralytic polio: 1. Spinal Polio: 80% of the cases, anterior horn injury 🡪 Flaccid paralysis (often lower limbs) 2. Bulbar Polio: 2% of the cases, cranial nuclei injury 🡪 Associated muscle weakness 3. Bulbospinal Polio: About 15% of the cases with a combination of symptoms  Poliovirus Diagnosis, Treatment, and Prevention Diagnosis: Isolation of virus from stool, throat, or CSF 🡪 Cell culture 🡪 PCR Treatment: No specific treatment 🡪 Supportive – Pain and muscle spasm control and release muscle contracture – Stabilization of flail and relaxed joints – Orthopedic support to prevent contractures, deformities, and fractures Vaccine: – Inactivated (Killed) Polio Vaccine IPV: Dr. Salk – Active against all 3 types – Oral (live) Polio Vaccine OPV: Dr. Sabin – Active against all 3 types – Before 2000 🡪 OPV – After 2000 🡪 IPV at 2, 4, 6 – 18 months and a booster 4 – 6 years.  IPV vs. OPV OPV IPV The Good The Good Oral (easy administration) >50% immunity after 2 doses No risk of vaccine associated polio >95% immunity after 3 doses Safe in immunocompromised patients Lifelong immunity >90% immunity after 2 doses No boosters necessary Humoral and intestinal immunity >99% immunity after 3 doses Attenuated copy may spread by contact, Easier to store and transport therefore, contributing to “herd immunity” The Bad The Bad Risk of vaccine – associated polio Booster needed (no lifelong) Can’t be administered to immunocompromised patients Injection Has to be store/transported at subzero Large dose required temperature No major storage requirements  Coxsackieviruses A large subgroup of enteroviruses causing a variety of diseases in humans Named after Coxsackie, NY where the virus group was discovered in 1949 The group of viruses is associated with a wide range of infections ranging from mild to severe, depending on the virus and serotype (mild rash to meningitis) Transmission: Fecal – oral (highly contagious) No vaccine No treatment (hand washing and sterilization)  Coxsackievirus Hand, foot, and mouth disease A9, A16 Aseptic meningitis (mostly in summer and fall) Coxsackievirus A Herpangina (1 – 24) Acute hemorrhagic conjunctivitis A24 Poliomyelitis – Like symptoms A7 Worldwide distribution All but one discovered in US (the sixth in Philippines) Coxsackievirus B (1 – 6) Pleurodynia Myocarditis (leading cause) and pericarditis May also be associated with FHM B2, B5 Juvenile diabetes (IDDM) – B4  Coxsackivirus Clinical manifestations HFM Herpangina Conjunctivitis Pleurodynia Vesicular rash on Fever, sore throat, Eye pain followed by Acute onset of fever, hands, feet, mouth, anorexia, vomiting. redness, teary unilateral low and tongue. painful eyes, swelling thoracic chest pain. Vesicular ulcerating and light sensitivity. Mild fever lesions on soft palate The pain is and uvula Highly contagious excruciating “Devil’s grip” Males may testicular pain.  Other Enteroviruses Enterovirus Clinical manifestation Enterovirus 68 Pneumonia + Motor neurons Enterovirus 69 Enterovirus 70 Acute hemorrhagic conjunctivitis Polio – like symptoms Enterovirus 71 Aseptic meningitis HFM – like symptoms  Rhinovirus One of the most common causes of the “common cold” More common during the “summer/fall” season (33-35°C) Unlike enteroviruses, Rhinovirus infections are localized to the nose Unlike enteroviruses, it can’t tolerate acid 🡪 can’t survive in GIT Transmission by contact with respiratory secretions Symptoms: Runny nose No treatment, no vaccine. (Too many serotypes – more than a 100) Plays a role in the development of childhood asthma and is a trigger for asthma exacerbations  Hepatitis A Virus Originally known as “Enterovirus – 72” Transmission: Fecal – oral Infects intestinal epithelial cells and spread to liver (blood) Symptoms: Sudden fever, jaundice 🡪 self – limiting (No chronic state) Associated with lifelong immunity (Anti Hep A IgG) No specific treatment Vaccine available since 1992 🡪 Inactivated virus. – Recommended for at risk groups – Some countries attempted an eradication program Hepatitis A Virus – Distribution  Caliciviridae RNA VIRUSES +ssRNA -ssRNA dsRNA Enveloped Nonenveloped Enveloped Nonenveloped Naked, icosahedral virus Reoviridae Flavirividae Resistant to heat and detergents Togaviridae Picornaviridae Orthomyxoviridae Paramyxoviridae Retroviridae Calicivridiae Rhabdoviridae Coronaviridae Caliciviridae Filoviridae Hepeviridae Bunyaviridae On the bright side, can be inactivated by acid Arenaviridae – pH 3 🡪 99% inactivation Most organisms (Norovirus, and Sapovirus) in the family are transmitted by fecal – oral rout Most viruses in the family are associated with gastrointestinal manifestation such as diarrhea and vomiting. Most infections are self – limiting Norovirus – Norwalk Agent First identified in Norwalk, OH in 1973 Associated with contaminated water supplies and food 🡪 Fecal-oral Very contagious and commonly associated with potluck meals, outbreaks on cruise ships. Resistant to heat and detergents Virus isolated from stool and vomit of infected patients Acute gastroenteritis 12 – 24 after ingestion of food 🡪 Watery diarrhea, N&V Self – limiting in 1 – 2 weeks, longer in the elderly and immunocompromised. Prevention: Good hygiene, handwashing  Hepatitis E Virus Used to be classified as a Caliciviridae It is considered a member of the Hepeviridae (+ssRNA) Fecal oral transmission, typically contaminated water source. Associated with contaminated water supplies Associated with epidemic Hepatitis (not common in US) Associated with a high mortality rate in infected pregnant women In developed countries, outbreaks have been linked to ingestion of undercooked pork or deer meat. (no outbreaks in the US)  RNA VIRUSES Reoviridae +ssRNA -ssRNA dsRNA A diverse family of viruses (15 known genera) Enveloped Nonenveloped Enveloped Nonenveloped causing infection in mammals, birds, reptiles, fish, amphibians and even plants. Reoviridae Reovirida Flavirividae Picornaviridae Orthomyxoviridae Togaviridae Calicivridiae Paramyxoviridae Retroviridae Rhabdoviridae Hepeviridae R E O refers to Respiratory Enteric Orphan viruses Coronaviridae Filoviridae Bunyaviridae Arenaviridae Double or triple protein-layered capsid 🡪 Resistant to environmental conditions Of interest to humans: – Rotavirus: Common cause of gastroenteritis is infants and young children (prior to vaccine) – Coltivirus: Associated with “Colorado Tick Fever” 🡪 Fever, myalgia, rash (Rodents)  Rotavirus Rota (wheel) Virus Transmission: fecal – oral (possible respiratory) Extremely common, nearly every child in the world There are 5 rotaviruses (A, B, C, D, E) – but A remains the most common 90% – Rotavirus A: Self-limiting, Infantile watery diarrhea with vomiting and fever – Rotavirus B: Adult onset of severe diarrhea s (epidemic in east Asia) Prevention: – Live, attenuated vaccine. – Administered orally at 2, 4, 6 months of age Incidence is declining due to introduction of Rotavirus vaccine  Colorado Tick Fever Virus A coltivirus belongs to Reoviridiae family Transmitted by: Dermacentor tick Region: Western US Reservoir: Small rodents (Squirrels, chipmunks, and mice) – Larger animals may be infected however they don’t transmit because of low viral titer 🡪 Dead-end host Incubation: Up to 20 days The virus infects RBC and cause viremia Clinical manifestations: (symptoms are self-limiting) – Spiking fever and chills (1-3 days apart) – Hepatomegaly, nausea, and vomiting – Aseptic meningitis and encephalitis  RNA VIRUSES Flaviviridae +ssRNA -ssRNA dsRNA Enveloped Nonenveloped Enveloped Nonenveloped Flaviviridae Reoviridae Flavirividae Pestiviruses Togaviridae Picornaviridae Orthomyxoviridae Calicivridiae Paramyxoviridae Retroviridae Rhabdoviridae Coronaviridae Hepeviridae Filoviridae Bunyaviridae Arenaviridae Flaviviridae Hepatitis C virus Flaviviruses Yellow fever virus (YFV) arboviruses Japanese encephalitis virus (JEV) St. Louis encephalitis virus (SLE) West Nile encephalitis virus (WNV) Dengue virus Zika virus  Dengue Virus Enveloped, +ssRNA (5 serotypes DENV-1 – DENV-5) Transmitted by female Aedes aegypti Estimated 390 million cases annually Endemic in more than 100 countries Over 2.5 billion people at risk for infection, 2/5 of the world’s population Case-fatality rate for DHF averages 5 percent and 58,000 deaths have been attributed to dengue in the past 40 years World Wide distribution of Dengue Fever  Dengue Virus Typical uncomplicated (Classic) – Fever within 4 – 7 days post exposure – Severe headache – Severe joint and muscle pain (break bone fever) – Nausea and vomiting – Rash Dengue hemorrhagic fever (may lead to death) Antibody dependent enhancement – Symptoms of classic dengue – Gingival and nasal bleeding – Increased menstrual flow – GI bleeding – Hematuria Antibody Dependent Enhancement (ADE) https://doi.org/10.3389/fimmu.2022.889196 Dengue Virus Diagnosis: Demonstration of IgM or IgG to one or more dengue virus antigens Detection of viral genomic sequence by RT-PCR Tourniquet Test (inflate BP to systolic + diastolic for 5 min, count petechial spots in 1 square inch Management: Most often, it is a self-limiting infection Control fever with antipyretics (avoid Aspirin, anti-platelet effect) Use insect repellent No antiviral treatment Currently there is no approved vaccine (many are in the works)  Flaviviridae (Summary of arboviruses) Virus Vector Host Clinical manifestations Diagnosis and Management St. Louis encephalitis virus Mosquito Birds Encephalitis Supportive West Nile encephalitis virus Mosquito Birds Encephalitis Supportive (they die) Dengue virus Mosquito Humans Dengue fever Supportive Dengue hemorrhagic fever Yellow Fever virus Mosquito Humans Yellow Fever (Jaundice) Supportive (live attenuated vaccine) Zika virus Mosquito Humans, Congenital microcephaly Supportive rodents Japanese encephalitis virus Mosquito Birds Encephalitis Supportive Pigs Vaccine in China Hepatitis C Virus Enveloped +ssRNA virus belonging to flaviviridae family of RNA viruses 6 genotypes (1 – 6) – Genotype 1 is most common in the US Transmission: Blood – borne May progress to chronic state – Cirrhosis – End – stage liver disease – Hepatocellular carcinoma Symptoms: Jaundice The most important cause of chronic liver disease in the US The most common cause of liver transplantation in US  Hepatitis C Lipid Encapsulation In vitro studies demonstrated the link between Hepatitis C virus and lipid metabolism HCV circulate in the serum of infected patients in association with host lipoproteins – Particluarly, VLDL and LDL to form lipo-viro-particle (LVP) The interaction with the host lipoproteins contributes to viral persistence 🡪 Chronic liver disease Additionally, viral antigens within the LVP are shielded from the immune response https://doi.org/10.3389/fimmu.2018.01436  AM EX Recommendations for One-Time Hepatitis C Testing T ON NO All patients born between 1945 and 1965 Risk Behaviors – Injection-drug use – Intranasal illicit drug use Risk Exposures – Patients on long-term hemodialysis – Patients with percutaneous/parenteral exposure in an unregulated setting (ie. tattoos, piercings) – Healthcare personnel after a needle stick – Children born to HCV-infected mother – Patients who have received transfusions or organ transplants prior to 1992 – Patient’s with a history of incarceration AASLD-IDSA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. Date accessed: 2/28/18  Management of HCV infection Spontaneous resolution of acute HCV infection may occur in 15 – 50% of patients 🡪 Wait 6 months before initiating treatment. HCV has become a curable (>97%) disease with use of antivirals. Liver biopsy is important for staging and treatment assessment Treatment is often dependent on signs and symptoms and liver biopsy In a cirrhotic patient, screen for hepatocellular carcinoma by ultrasound and monitoring AFP every 6 months. Almost always, HCV infection recurs in patients with liver transplant  Togaviridae RNA VIRUSES +ssRNA -ssRNA dsRNA Enveloped Nonenveloped Enveloped Nonenveloped Orthomyxoviridae Reoviridae Flavirividae Picornaviridae Togaviridae Togaviridae Calicivridiae Paramyxoviridae Rubella Retroviridae Hepeviridae Coronaviridae Rhabdoviridae German measles Filoviridae Bunyaviridae Arenaviridae Rubivirus Host Chikungunya virus Primates, rodents Togaviridae Alphavirus Eastern equine encephalitis virus Western equine encephalitis virus Birds and Horses Venezuelan equine encephalitis virus Arboviruses Killed vaccine available for EEE, WEE  Rubella Virus A rubivirus transmitted by contact with respiratory droplets Mild course and may be asymptomatic (up to 70%) Clinically characterized by a maculopapular rash – The rash begins on the face and spreads to trunk, extremities – Fever maybe mild or not present – The rash fades away in few days – Often accompanied by occipital and post auricular lymphadenopathy  Congenital During Pregnancy During the viremic stage, the virus cross the placenta Infection of any or all fetal germ layers results congenital abnormalities, premature deliver, and may lead to spontaneous abortion Severity of the symptoms depends on fetal age at time of maternal viremia Vertically transmitted infections Toxoplasma gondii Almost 100% risk of infection Other infections 1st Trimester 85% of infection result in congenital abnormality Congenital cardiac defects (Patent ductus arteriosus) Eneroviruses VZV 20% of infections result lead to spontaneous abortion P-B19 13 – 16 weeks Increased risk of deafness and retinopathy (cataracts) HIV Chlamydia trachomatis > 4 months Slight risk of deafness and retinopathy (cataracts) Treponema pallidum Listeria monocytogenes Neisseria gonnorheae Prevention: MMR at 12-18months and a second dose at 4-6 years GBS Rubella CMV HSV-2  RNA VIRUSES Coronavirus +ss RNA -ss RNA dsRNA 11/2002 SARS-CoVFirst case in china Enveloped Nonenveloped Enveloped Nonenveloped 2/2003 305 cases, 5 death 3//2003 Spread to Honk Kong, Singapore Flavirividae Orthomyxoviridae Reoviridae 3//2003 WHO issues global SARS-CoV alert Togaviridae Picornaviridae Calicivridiae 4//2003 3000 cases in China Retroviridae Paramyxoviridae 4//2003 Signs of peaking Coronaviridae Coronaviridae Rhabdoviridae Filoviridae 6//2003 Alert lifted for most countries Bunyaviridae Arenaviridae 11//2019 SARS-CoV2 Largest genome among RNA viruses Spike protein 🡪 Cell fusion (possible vaccine target) 3 – 4 days incubation Mainly associated with upper respiratory infection SARS-CoV first virus associated with LRI Unconfirmed GI association in humans Coronaviridae Corovavirus Torovirus  Coronavirus - Epidemiology Natural outbreaks of colds caused by coronaviruses occur predominantly during the winter months, although in children, two peaks in late autumn to early winter and early summer were detected. It is estimated that coronaviruses cause 15–30% of all colds. Studies using virus detection or serology have shown that HCoV 229E, OC43, and NL63 occur worldwide Novel coronavirus known as SARS-CoV-2 was identified in Wuhan, China when people developed pneumonia-like symptoms The five VOCs, including the original Omicron (B.1.1.529), show 75 genetic mutations. Most changes are to the spike protein gene and receptor-binding domain Sep 2020 Oct 2020 Nov 2020 Oct 2020 Nov 2021 https://microbenotes.com/coronavirus/  SARS-CoV-2 SARS-CoV-2 Spike proteins utilize angiotensin converting enzyme 2 (ACE2) receptor. Transmission primarily via respiratory droplets, face contact, and, to a lesser degree, via contaminated surfaces. An estimated 48% to 62% of transmission may occur via presymptomatic carrier (unlike SARS-CoV1) resulting in an expanded pandemic  Common symptoms in hospitalized patients include: – fever (70%-90%), – dry cough (60%-86%), – shortness of breath (53%-80%), – fatigue (38%), – myalgias (15%-44%), – nausea/vomiting or – diarrhea (15%-39%), – headache, weakness (25%), – rhinorrhea (7%). – Anosmia may be the sole presenting symptom in approximately 3% of individuals with COVID-19. Common laboratory abnormalities among hospitalized patients include: – lymphopenia (83%), – elevated erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) – Elevated tumor necrosis factor-α, IL-1, IL-6), – abnormal coagulation (prolonged pt, thrombocytopenia and elevated D-dimer (46%) low fibrinogen)  RNA VIRUSES Filoviridae +ssRNA -ssRNA dsRNA “6” or “U”-shaped filamentous particles Enveloped Nonenveloped Nonenveloped Endemic in different regions in Africa Enveloped Includes: Reoviridae Flavirividae Picornaviridae Orthomyxoviridae Togaviridae Calicivridiae Paramyxoviridae Retroviridae – Ebolavirus (identified in 1976) Coronaviridae Hepeviridae Rhabdoviridae Filoviridae Filoviridae – Marburg virus (identified in Germany Bunyaviridae Arenaviridae 1967, origin traces to South Africa) – Cuevavirus (2011 spain, distant relative?) Ebola circulates in wild animal hosts – Reservoir: Bats – Host: Primates  Filoviridae Transmission: Person – to – person (contact with contaminated bodily fluids) Signs and symptoms of Ebola: Hemorrhagic Fever – Early: Muscle aches, fever, vomiting, red eyes, skin rash – Acute: Bleeding, skin hemorrhage Treatment: – No FDA approved vaccine or medicine – Provide IV fluids and balance electrolytes – Maintain ventilation and perfusion – Manage infections – Upon recover, antibodies may last up to 10 years or longer – In the recent outbreak (2014) Dr. Kent Brantly recovered after receiving a transfusion from a survivor – Vaccine became available in December 2019  RNA VIRUSES Orthomyxoviridae +ssRNA -ssRNA dsRNA -ssRNA, segmented 🡪 Reassortment Enveloped Nonenveloped Enveloped Nonenveloped Reoviridae Endemic and pandemic respiratory infections Flavirividae Orthomyxoviridae Orthomyxoviridae Togaviridae Picornaviridae Calicivridiae Paramyxoviridae Retroviridae Rhabdoviridae Coronaviridae Hepeviridae Filoviridae Three types of influenza Bunyaviridae Arenaviridae Influenza A Humans, birds, swine, etc. Influenza B Only found in humans (mild) Influenza C Mainly humans?? (rare, milder) Matrix protein (M2) (HA) Matrix protein (M1) (NA) Shift vs. Drift Antigenic Drift Small, constant point mutations Gradual change in amino acid composition Results in minor antigenic change leading to epidemics Seen in all 3 types of influenza Annual vaccination Antigenic Shift Substitution of gene segments with segments from another influenza virus from a different host 🡪 REASSORTMENT Only seen with influenza type A Pandemics Less common  What is in the name? Influenza Lingo The nomenclature system includes the following: – Host origin – Geographic location of the first isolate – Strain number – Year of isolation Also included is the hemaglutinin and neuroaminidase subtypes Examples: 2022 – 2023 Flu season: A/Victoria/4897/2022 (H1N1) A/Wisconsin/67/2022 (H1N1) A/Darwin/6/2021 (H3N2)  Influenza Pathogenesis Transmission: Person to person, direct contact, aerosol droplets Infects respiratory epithelial cells Incubation: 1 – 4 days Virus detected just before onset of symptoms Virus not detected 5 – 10 days after symptoms Longer shedding in children, elderly Typical season: 200,000 hospitalizations Typical season: 36,000 deaths  Influenza – Clinical Manifestations Fever Headache Chills Muscle ache General fatigue Runny nose (as the fever declines) Coughing (as the fever declines) Complications: Bronchitis, Pneumonia Treatment: Amantidine (target M2) no longer recommended due to resistance Zanamivir (Relenza®), Oseltamivir (Tamiflu®) 🡪 Target neuroamindase (works on A, B) Vaccines are updated annually 🡪 Vaccination needed each year – Flu shot 🡪 whole inactivated virus – Flumist 🡪 Live attenuated  RNA VIRUSES Paramyxoviridae +ssRNA -ssRNA dsRNA Enveloped Nonenveloped Enveloped Nonenveloped Reoviridae Flavirividae Picornaviridae Orthomyxoviridae Togaviridae Calicivridiae Paramyxviridae Paramyxoviridae Retroviridae Rhabdoviridae Coronaviridae Hepeviridae Filoviridae Bunyaviridae Arenaviridae Rubulavirus Mumps, Parainfluenza 2, Parainfluenza 4 Paramyxovirinae Respiviruss Parainfluenza 1, Parainfluenza 3 Morbilivirus Measles Paramyxoviridae Henipavirus Hendra virus, Nipah virus Pneumovirus RSV Pneumovirinae Metapneumovirus Human metapneumovirus The Structure of a Paramyxoviridae Virus Mumps virus Paramyxoviridae Rublavirus Mumps virus Causes an acute viral illness associates with parotitis and orchitis One antigenic type (easily controlled by immunization) Rapidly inactivated by high temperature, UV ray, and chemical agents May be associated with seasonal pattern during late winter and spring  Mumps virus – Pathogenesis Reservoir: Human Respiratory transmission Incubations: 14 – 18 days Replicates in cells of the nasopharynx Viremia in 12 – 25 days Multiple tissue infected Symptoms: (up to 20% asymptomatic) Nonspecific, myalgia, headache Parotitis in 30 – 40% Complications: Orchitis 20 – 50 in post – pubertal males CNS involvement in 15% 🡪 Encephalitis Pancreatitis 2 – 5 % Death 2006 Mumps virus outbreak in the US  Measles Virus Paramyxoviridae Mrobilivirus Measles virus Highly contagious virus (during prodromal period) A major cause of vaccine – preventable death in children No animal reservoir 🡪 Human respiratory tract Transmission by respiratory droplets, nasal secretions Only one serotype Measles virus Clinical course Rash – starts at neck/face & moves down; can CCC & P = cough, coryza, become confluent conjunctivitis & Koplik spots – usually precede rash; photophobia can overlap with it  Measles – Clinical Signs Cough, coryza (inflammation of mucosa, conjunctivitis (3 C’s) Koplik spots – small white spots in the buccal mucosa High fever (40°C) Generalized maculopapular rash rom the airs down Complications: Diarrhea Otitis media Pneumonia Subacute sclerosing panencephalitis Death Prevention: Live att. MMR 12mo, 15mo, 4yr.  Parainfluenza virus Respiratory transmission One of the most common causes of laryngotracheobronchitis (Croup) characterized by a dry barking cough and hoarse voice. Peak incidence: 6-months to 6-years in the winter (and fall) Diagnosis: Detection of viral antigens in nasopharyngeal aspirates Management is supportive No vaccine available  Respiratory Syncytial Virus Most common cause or LRI in infants and kids (