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Viral Infections of the Respiratory System Clinical manifestations Common cold (rhinitis) Pharyngitis Tonsilitis Sinusitis & otitis media Croup (acute laryngotracheobronchitis) Acute bronchitis Acute bronchiolitis Viral pneumonia Influenza (Flu) The common respiratory viruses Name of the virus Family Disease 1- Influenza virus Orthomyxoviridae URT & LRT infection 2- Parainfluenza virus Paramyxoviridae URT & LRT infection 3- Respiratory syncytial virus Paramyxoviridae LRT infection 4- Rhinovirus Picornaviridae URT infection 5- Coronavirous Coronaviridae URT infection 6- Adenovirus Adenoviridae URT and eye infections 7- Human metapneumovirus Paramyxoviridae LRT infection Upper respiratory tract infection includes rhinitis (common cold), tonsillitis, pharyngitis Lower respiratory tract infection includes croup, bronchitis, bronchiolitis, pneumonia ORTHOMYXOVIRIDAE Orthomyxoviruses are spherical, enveloped viruses containing a segmented, negative strand RNA genome Viruses in this family infect humans, horses, and pigs, and are the cause of influenza Orthomyxoviruses are divided into three types: Influenzae A, B, and C Only influenza virus types A and B are of medical importance Type A influenza viruses differ from type B viruses in that they have an animal reservoir and are divided into subtypes Influenza virus C is not a significant human pathogen Structure Influenza virions are spherical, enveloped, pleomorphic particles Two types of spikes project from the surface One is composed of H protein and the second of N protein Both the H and N influenza proteins are integral membrane proteins The M (matrix) proteins underlie the viral lipid membrane The RNA genome, located in a helical nucleocapsid, is composed of eight distinct segments of RNA Each of which encodes one or more viral proteins Each nucleocapsid segment contains not only the viral RNA but also four proteins Influenza Virus Orthomxoviridae family They are helical, enveloped, single stranded RNA genome They are enclosed in a lipid envelop and a layer of glycoprotein spikes known as haemagglutinin (HA) and neuraminidase (NA), which are major antigenic determinants They are divided into different genera on the basis of the nucleoprotein antigen Genera A, B, C Pathogenesis The virus infects the epithelial cells of the nose, throat, bronchi and occasionally the lungs Clinical Significance Influenza spread by respiratory droplets and is an infection solely of the respiratory tract There is rarely viremia or spread to other organ systems Influenza has an acute onset, with symptoms including a nonproductive cough and chills, followed by high fever, muscle aches, and extreme drowsiness Runny nose is unusual, differentiating influenza virus infection from the common cold The disease runs its course in 4 to 5 days, after which recovery is gradual The most serious problems, such as development of pneumonia or bacterial pneumonia Influenza Virus Electron micrograph. Electron micrograph. Influenza viral proteins Haemagglutinin (H) Attachment to the cell surface receptors Antibodies to the HA is responsible for immunity 16 haemagglutinin antigenic type, H1 – H16 Human associated H antigenic type are H1, H2, H3 Neuraminidase (N) Responsible for release of the progeny viral particles from the infected cell 9 neuraminidase antigenic type, N1 – N9 Human associated N antigenic type are N1, N2 Summary of the ecology of influenza viruses Prevention Influenza vaccine: Two types of vaccines available 1- The flu shot vaccine: Inactivated (killed vaccine) Given to people older than 6-months, including healthy people and those with chronic medical conditions 2- The nasal spray flue vaccine: Live attenuated vaccine Approved for use in healthy people between 5-49 years of age Both vaccines contain two strains of the current circulating influenza A and B viruses Vaccine should be given in October or November before the influenza season begins Role of H AND N Proteins H = Hemagglutinin and N = Neuraminidase Hemagglutinin allows the virus to bind to host cells Neuraminidase helps the virus to release itself from the highjacked cells in which it has reproduced Influenza A Virus Constantly Changes Antigenic drift Small changes in H or N proteins that occur from year to year Population is partially immune, but may be re-infected over time (periodic epidemics) Antigenic shift Acquisition of new H or N protein, possibly from an animal virus Population is not immune, everyone is susceptible (pandemics) Influenza A Virus Influenza A virus only is further classified into subtypes based upon HA and NA antigens 16 HA subtypes and 9 NA subtypes are now recognized circulating in birds, humans, swine and horses The most famous subtypes are: A (H1N1): circulating in humans causing swine flu A (H5N1): circulating in birds causing avian flu Clinical picture • Fever • Headache • Myalgia • Cough • Rhinitis • Ocular Symptoms Incubation period: 1 to 2 days Transmission: droplet infection or hand-to-hand contact Diagnosis: 1- Isolation of the virus from nose, throat swab 2- Tissue culture 3- Provisional - clinical picture + outbreak Avian flu Viral etiology: Avian influenza type A virus (H5N1) Family: orthomyxovirus Epidemiology Wild birds are the natural reservoir for the virus They shed the virus in saliva, nasal secretion and feces • All domestic poultry are susceptible to infection • They become infected, when they eat food contaminated with secretion from infected bird • Avian influenza viruses do not usually infect human • High risk group includes those who working in poultry farms and those who are in close contact with poultry Symptoms in human Ranges from typical flu to severe acute respiratory disease Diarrhea, abdominal pain and bleeding from the nose have been reported Treatment Should be initiated within 48 hours Lab diagnosis PCR, detection of the viral RNA in throat swap Parainfluenza Virus Family: Paramyxoviridae Structural features Enveloped virus with - ssRNA genome, with 5 serotypes Transmission Inhalation of infectious aerosol droplets mainly in winter Clinical syndrome a. Croup (or laryngotracheobronchitis) b. Fever, harsh cough, difficult inspiration can lead to airway obstruction need hospitalization to do tracheostomy c. Bronchiolitis and Pneumonia Lab diagnosis Direct detection immunofluorescence Treatment and prevention Supportive treatment, No specific treatment or vaccine available Respiratory Syncytial Virus (RSV) Family: Paramyxoviridae Structural features: Enveloped virus with - ssRNA genome Transmission: Inhalation of infectious aerosols mainly in winter Clinical syndromes: a. Bronchiolitis a. Life-threatening disease in infant especially under 6 month of life with respiratory distress and cyanosis can be fatal and can lead to chronic lung disease in later life b. Pneumonia a. can also be fatal in infant Lab diagnosis Isolated of virus by cell culture Direct detection of the Ag by direct I.F. Treatment and prevention Ribavirin administered by inhalation for infants with severe cases Vaccine No vaccine available, but passive immunization immunoglobulin can be given for infected premature infants Rhinovirus Family: Picornaviridae Structural features: Non-enveloped virus with + ssRNA genome, more than 100 serotypes available Transmission: Inhalation of infectious aerosol droplets Clinical symptoms: The 1st cause of common cold. The main symptoms of common cold are sneezing, clear watery, nasal discharge with mild sore throat, and cough Lab diagnosis: Direct detection of the Ag by direct I.F. Treatment and prevention: Usually self-limiting disease, no specific treatment, and no vaccine available Coronavirus Family: Coronaviridae • Structural features: They are large helical, enveloped, single stranded RNA viruses Transmission: Inhalation of infectious aerosol droplets Clinical symptoms: The 2nd cause of common cold. The human coronaviruses (CoVs) are responsible for about 30% of mild upper respiratory tract illness (common cold) • Severe Acute Respiratory Syndrome (SARS) • Newly emerged SARS-CoV causes severe acute respiratory syndrome (SARS) that has been reported in Asia, North America, and Europe In winter of 2002, a new respiratory disease known as (SARS) emerged in China A new mutation of coronavirus MERS-CoV, with probably an animal reservoir, and cause atypical pneumonia with difficulty in breathing Treatment and prevention: No specific treatment or vaccine available, yet SARS Disease Severe acute respiratory syndrome (SARS) viral respiratory disease zoonotic origin caused by the SARS coronavirus (SARS-CoV) Incubation period: 2 - 10 days Transmission: droplet infection or contact to contaminated skin or fomites Clinical Picture Fever, chills, headache, myalgia and malaise Respiratory symptoms often begin 3-7 days after symptom onset and peak in the second week Laboratory Diagnosis Serological Testing Molecular Testing IFA: Indirect fluorescent antibody ELISA: Enzyme-linked immunosorbent assays RT-PCR: Reverse transcriptase-PCR Culture: SARS-CoV (Vero E6 cell) Adenovirus Family: Adenoviridae Structural features: Non-enveloped virus with ds-DNA genome Pathogenesis: Adenovirus infects epithelial cell lining respiratory tract, conjunctiva, urinary tract, gastrointestinal tract and genital tract. Clinical syndrome 1. Phrayngitis and tonsilitis 2. Pharyngioconjunctivitis 3. Keratoconjunctivitis 4. Pneumonia: in preschool children 5. Gastroenteritis 6. Acute hemorrhagic cystitis 7. Cervicitis and urethritis Treatment and prevention: No specific treatment or vaccine