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30 Cards in this Set
- Front
- Back
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Respiratory Viruses and
Clinical Syndromes Link of virus to syndrome: • Rhinovirus - • Coronavirus - • Adenovirus - • Parainfluenza virus - • Influenza virus - • Respiratory syncytial virus • Human metapneumovirus |
• Rhinovirus - Common cold
• Coronavirus - Common cold, croup, SARS • Adenovirus - Pharyngitis • Parainfluenza virus - Croup, laryngitis • Influenza virus - Influenza • Respiratory syncytial virus - Bronchiolitis, pneumonia • Human metapneumovirus - Bronchiolitis |
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T/F
Viral infections are more frequent in children than adults T/F Association with bacterial infections such as otitis media, sinusitis, pneumonia |
True
True |
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RSV infections predominate around what time of the year?
Last how long? Influenza A/B infections predominate around what time of the year? Last how long? |
RSV: starts in nov, lasts ~ 4 months
Influenza A/B: nov-march; lasts about 12 weeks |
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RHINOVIRUS - VIROLOGY
envelope? dna/rna? serotypes? capsid? site of attachment? what cellular receptors do they interact with? Lab cultivation: optimal replication temp? |
- Picornaviridae
• Non-enveloped • Single-stranded, positive-sense RNA genome • 101 serotypes - Icosahedral capsid composed of 4 proteins (VP 1-4) - Site of attachment to cells is within a cleft present in structural subunits - Cellular receptors, - ICAM-1 (91 serotypes), low-density lipoprotein receptor (all but one of the other serotypes) - Lab cultivation – optimal replication at 33-35°C |
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Epidemiology of Rhinovirus
How many per year? age group? Seasonal? peaks when? Where is virus present? Transmission through? _____ and _____ inoculations are more effective than ____ inoculations |
• Frequent – Several per year, especially in children
• Seasonal: Peaks in late fall and early spring • Transmission - Virus is present in nasal secretions - Hands and environment become contaminated - Nasal and ocular inoculation are more effective than oral inoculation |
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Rhinovirus – Clinical Manifestations
Symptoms? Complications? |
Symptoms
• Nasal stuffiness • Runny nose (coryza) • Sneezing • Sore throat • Low grade fever Duration usually less than 1 week Complications • Sinusitis • Otitis media • Exacerbations of asthma and chronic lung disease • May cause hospitalization, especially in young children and asthmatics |
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Rhinovirus – Diagnosis and Treatment
_____ is much more sensitive than culture (may increase detection by 3-4 fold) but is still not in routine use. Most cases do not require laboratory diagnosis Treatment is symptomatic - (2) Antiviral drug _______ has activity but has not yet been shown to be clinically effective |
• Laboratory diagnosis - cell culture. Antigen detection not applicable because of strain diversity.
RT-PCR is much more sensitive than culture (may increase detection by 3-4 fold) but is still not in routine use. • Most cases do not require laboratory diagnosis • Treatment is symptomatic - first generation antihistamines, NSAIDs • Antiviral drug pleconaril has activity but has not yet been shown to be clinically effective |
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Influenza - Virology
Envelope? Genome? • _ types exist, designated _-_ T/F Each RNA segment contains a specific gene that encodes one or more proteins? • Replication occurs where? • Surface proteins are _______ and ________? • Natural reservoir is _____? |
• Orthomyxoviridae
• Enveloped • Segmented, single-stranded, negative-sense RNA genome • 3 types exist, designated A-C • Each RNA segment contains a specific gene that encodes one or more proteins • Replication occurs in nucleus of infected cells • Surface proteins are hemagglutinin and neuraminidase • Natural reservoir is birds |
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Influenza Classification
Types A, B, C defined by antigenic differences in the ________ • Type A is divided into subtypes based on _________ and __________ |
Types A, B, C defined by antigenic differences in the nucleoprotein
• Type A is divided into subtypes based on hemagglutinin (H) and neuraminidase (N) |
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Antigenic Shift and Drift
Shift/Drift: Result from? Other differentiating features? |
Shift
• Complete change in hemagglutinin or neuraminidase gene • Results from genetic reassortment • Pandemic disease may occur Drift • Change in antigenicity of hemagglutinin or neuraminidase gene • Results from point mutation • May or may not cause preexisting immunity to become ineffective |
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______ are susceptible to both avian/human influenza - may be reservoir for recombination/mixing of viruses
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Swine
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Epidemiology of Influenza
• Seasonal? • Outbreaks last ____ weeks, rare between outbreaks • Contagious? • Transmission? |
• Highly seasonal
• Outbreaks last 8-12 weeks, rare between outbreaks • Highly contagious • Airborne transmission |
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Community Impact of Influenza Outbreaks
Increases in: |
• Work absenteeism
• School absenteeism • Emergency room visits • MD office visits • Hospital respiratory admissions • Pneumonia and influenza mortality • Total mortality |
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Influenza - Pathogenesis
• Cytopathic infection of _______ cells • Causes damage to ________? • Constitutional symptoms may be related to cytokine elaboration, especially _________ (3) • Bacterial superinfection can occur, esp. ____________? |
• Cytopathic infection of respiratory epithelial cells
• Causes damage to respiratory mucosa • Constitutional symptoms may be related to cytokine elaboration, especially IL-6, TNFα, IL-1 • Bacterial superinfection can occur, esp. pneumonia |
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Human influenza strains bind preferentially to _________?
whereas avian strains bind preferentially to _____. The receptor binding preference has a major effect on ____________ |
human influenza = sialic acid α-2,6 linkages
avian strains = α-2,3 linkages The receptor binding preference has a major effect on transmisssibility |
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Influenza – Treatment
Name the 4 Drugs |
Amantadine and rimantadine
(M2 inhibitors) Neuraminidase inhibitors - zanamavir and oseltamivir |
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Treatment of Influenza
Amantadine and rimantadine (___ inhibitors)? • Effective ONLY against type ___? • Act ____ in replication cycle, interact with __ protein to block viral ________? • Resistance emerges readily and is now common in ____ and ____ strains. Thus these drugs are not currently recommended for use. |
Amantadine and rimantadine
(M2 inhibitors) • Effective ONLY against type A • Act early in replication cycle, interact with M2 protein to block viral uncoating • Resistance emerges readily and is now common in H1N1 and H3N2 strains. Thus these drugs are not currently recommended for use. |
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Treatment of Influenza
Neuraminidase inhibitors - _______ and _________? • Effective against __ and ___? • Must be started within first ___ hours • Can also be used for _______? • Resistance has emerged in ____ and ____ strains. It is related to a specific mutation in the _________ gene (H274Y) |
• Neuraminidase inhibitors - zanamavir and oseltamivir
• Effective against A and B • Must be started within first 48 hours • Can also be used for prophylaxis • Resistance has emerged in H5N1 and H1N1 strains. It is related to a specific mutation in the neuraminidase gene (H274Y) |
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Influenza Vaccines
How are these administered: Inactivated? live/attenuated? Current vaccine is __-valent? Consists of? |
• Inactivated (intramuscular) or live attenuated (nasal)
• Prepared from egg-grown virus • Reformulated yearly • Current vaccine is trivalent • A H3N2 • A H1N1 • B • Administered yearly |
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Influenza Vaccine Strategies
Traditional strategy? Revisionist strategy? |
• Traditional
– Protect high risk groups (elderly, those with chronic diseases) • Revisionist – Interrupt transmission by immunizing children |
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Influenza Vaccine
Target Groups for inactivated vaccine? For live attenuated? |
Inactivated vaccine (IM)
2 most important: • 50 years of age and older • Household contacts of children less than 5 years of age and adults ≥ 50 years of age Others: • Residents of nursing homes and chronic care facilities • Chronic pulmonary or cardiovascular renal, hepatic, hematologic, metabolic disease, or neuromuscular disease • Immunosuppressed individuals • Children 6 months -18 years of age • Long-term aspirin • Pregnant women who will be in the second or third trimester during influenza season • Household contacts of others at high risk for influenza complications Attenuated vaccine (nasal) • Healthy individuals 2-49 years of age |
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Respiratory Syncytial Virus - Virology
Envelope? Capsid? Genome? Important Proteins? (2) |
• Enveloped, helical nucleocapsid
• Genome: singlestranded RNA, negative sense, NONsegmented (unlike influenza) • 10 proteins, including G, the attachment protein and F, the fusion protein |
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RSV - Epidemiology
Seasonal? Duration? How common in children by age of 2? Reinfections common? Transmission? Nosocomial? |
• Annual winter epidemics, lasting approximately 5 months
• All children infected within first 2 years of life • Reinfections occur frequently • Transmission by contaminated secretions and large droplets • Nosocomial infections can occur |
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RSV – Clinical Manifestations?
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• Bronchiolitis
• Pneumonia • Non-specific upper respiratory infection • Apnea in young infants • Severe illness in infants with chronic cardiac or pulmonary disease • Increasingly recognized in adults |
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Risk Factors for Severe RSV
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• Congenital heart disease
• Chronic lung disease • Immunodeficiency • Prematurity • Age < 6 weeks • Neurologic or metabolic disease • Major congenital anomalies |
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RSV - Pathophysiology
• Infection of ________ cells results in obstruction of small airways from _____ and ______ ______ • ____-_____ _______ is required for clearance of virus, but also contributes to disease manifestations • __________ and ______ , e.g RANTES, are involved (may mediate symptoms) |
• Infection of respiratory epithelial cells results in obstruction of small airways from edema and cellular debris
• Cell mediated immunity is required for clearance of virus, but also contributes to disease manifestations • Cytokines and chemokines, e.g RANTES, are involved |
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RSV – Laboratory Diagnosis
• __________ is more sensitive than culture – ________ is currently the most widely used technique • Specimen is ________ or ____? |
• Antigen detection is more sensitive than culture – fluorescent antibody stain is currently the most widely used technique
• Specimen is nasopharyngeal aspirate or swab |
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Treatment of RSV
• ______ is an antiviral drug delivered by ________ that is active against RSV. It is rarely used except in ______________ patients. • Main treatment is _______: • Bronchodilators are often (effective/ineffective) ? • Corticosteroids have been shown to be (effective/ineffective?) in the past, but their use is currently being reevaluated |
• Ribavirin is an antiviral drug delivered by aerosol that is active against RSV. It is rarely used except in stem cell transplant recipients and other severely immunocompromised patients.
• Main treatment is supportive: oxygen, hydration, mechanical ventilation when needed • Bronchodilators are often ineffective • Corticosteroids have been shown to be ineffective in the past, but their use is currently being reevaluated |
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RSV - Prevention
Vaccines? What is given to premature infants and those with chronic lung disease during the RSV season to prevent infection? |
Vaccines are under development
• Live attenuated vaccine used in 1960s caused worse disease • Humanized monoclonal antibody (palivizumab) is given to premature infants and those with chronic lung disease during the RSV season to prevent infection |
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Palivizumab (Synagis®)
What is this agent? Used for? Indications? Administration? Cost? |
• “Humanized” monoclonal antibody
• Used to prevent RSV • Indications: - Extreme prematurity - Chronic lung disease • Administered by IM injection, once per month for entire RSV season • Expensive |
