Viral Upper Respiratory Tract Infections Manuel R. Amieva, M.D., Ph.D. Department of Pediatrics, Infectious Diseases Department of Microbiology & Immunology Stanford University School of Medicine Sharon F. Chen, M.D. Department of Pediatrics, Infectious Diseases Stanford University School of Medicine Charles G. Prober, M.D. Department of Pediatrics, Infectious Diseases Department of Microbiology & Immunology Stanford University School of Medicine 2 Learning Objectives • Describe a general model for the pathogenesis of viral respiratory tract infections that explains the symptoms and clinical manifestations. • Relate the epidemiology and clinical manifestations to the pathogenesis of viral respiratory tract infections caused by: Rhinoviruses Coronaviruses Adenoviruses Parainfluenza viruses 3 Major Human Pathogens Viruses Fungi Gram positive Bacteria RNA Influenza A, B Mold Rods Rhinovirus Branching Coxsackie Parainfluenza DNA Yeast Aspergillus Dimorphic Listeria Actinomyces RSV Coccidioides Cocci Enteroviruses Adenovirus Candida Mucor Bacillus Nocardia Human Histoplasmosis Poliovirus Herpes simplex Cryptococcus Rhizopus Staphylococcus Clostridium metapneumovirus Blastomyces Rotavirus Varicella zoster Pneumocystis Fusarium Streptococcus Corynebacterium Coronavirus Paracoccidioides Norovirus Cytomegalovirus Malassezia Enterococcus Gardnerella (MERS, SARS) Sporothrix Hepatitis A Epstein Barr virus Microsporidia Propionibacterium Hepatitis C Ebola HHV6, HHV7, HHV8 Dermatophytes HIV Rabies Smallpox Microsporum, Epidermophytum Trichophytum HTLV-1 Vector borne Molluscum contagiosum No cell wall Acid Fast Bacilli Measles West Nile Hepatitis B Mumps Parvovirus Pleomorphic Dengue Protozoa Tissue Mycobacterium tuberculosis Rubella Human papillomavirus Chickengunya Trypanosoma Mycoplasma Mycobacterium leprae Yellow Fever BK polyomavirus GI/GU Non-tuberculous Mycobacteria Entamoeba Blood Leishmania Toxoplasma Giardia Plasmodium Cryptosporidium Babesia Trichomonas Gram negative Bacteria Zoonotic Spirochaetes Arthropods Brucella Rods Francisella Campylobacter Treponema Ticks Helminths Enteric flora Pasteurella Borrelia Vectors of: Lyme borreliosis, Trematodes (Flukes) Nematodes E. coli Respiratory Pathogens Bartonella Leptospira Relapsing Fever, RMSF, Haemophilus other Rickettsia, Babesia, Schistosoma (Roundworms) Klebsiella Yersinia (Schistosomiasis) Bordatella Spiral Anaplasma, Ehrlichia Enterobius (Pinworm) Proteus Coxiella Clonorchis & Fasciola Legionella Campylobacter Intracellular Lice (pediculosis) Trichuris (Whipworm) Serratia Chlamydophila (Liver Flukes) Helicobacter Chlamydia Vectors of: Epidemic typhus, Ascaris (Giant worm) Enterobacter psittaci Paragonimus (Lung Fluke) Trench Fever Ancylostoma & Necator Opportunistic Rickettsia Chlamydophila Mites (scabies) (Hookworm) Pseudomonas Ehrlichia Rickettsia Coxiella Vectors of: Scrub typhus, Cestodes (Tapeworms) Strongyloides (Strongy) Anaplasma Rickettsialpox Enteric pathogens Legionella Taenia saginata Toxocara (Dog Ascaris) Comma Borrelia Mosquitoes (Beef Tapeworm) Trichinella (Trichinosis) Shigella Leptospira Ehrlichia Vectors of: Malaria, Dengue, Salmonella Vibrio Anaplasma Taenia Solium Onchocerca (River Anaerobic Chikungunya, West Nile, (Pig Tapeworm) Yersinia Bartonella Blindness) Yellow Fever Diphyllobothrium Loa Loa (Eye Worm) Bacteroides Brucella Fleas Diplococci (Fish Tapeworm) Wuchereria & Brugia Prevotella Francisella Vectors of: Cat-scratch fever, Neisseria Echinococcus (Elephantiasis) Fusobacterium Shigella Murine typhus, Bubonic Moraxella (Dog Tapeworm) Salmonella plague, Tularemia Major Human Pathogens Viruses Fungi Gram positive Bacteria RNA Influenza A, B Mold Rods Rhinovirus Branching Coxsackie Parainfluenza DNA Yeast Aspergillus Dimorphic Listeria Actinomyces RSV Coccidioides Cocci Enteroviruses RSV Adenovirus Candida Mucor Bacillus Nocardia Human Histoplasmosis Poliovirus Human Herpes simplex Cryptococcus Rhizopus Staphylococcus Clostridium metapneumovirus Blastomyces Rotavirus Varicella zoster Pneumocystis Fusarium Streptococcus Corynebacterium Coronavirus Paracoccidioides Norovirus Cytomegalovirus Malassezia Enterococcus Gardnerella (MERS, SARS)SARS) Sporothrix Hepatitis A Epstein Barr virus Microsporidia Propionibacterium Hepatitis C Ebola HHV6, HHV7, HHV8 Dermatophytes HIV Rabies Smallpox Microsporum, Epidermophytum Trichophytum HTLV-1 Vector borne Molluscum contagiosum No cell wall Acid Fast Bacilli Measles West Nile Hepatitis B Mumps Parvovirus Pleomorphic Dengue Protozoa Tissue Mycobacterium tuberculosis Rubella Human papillomavirus Chickengunya Trypanosoma Mycoplasma Mycobacterium leprae Yellow Fever BK polyomavirus GI/GU Non-tuberculous Mycobacteria Entamoeba Blood Leishmania Toxoplasma Giardia Plasmodium Cryptosporidium Babesia Trichomonas Gram negative Bacteria Zoonotic Spirochaetes Arthropods Brucella Rods Francisella Campylobacter Treponema Ticks Helminths Enteric flora Pasteurella Borrelia Vectors of: Lyme borreliosis, Trematodes (Flukes) Nematodes E. coli Respiratory Pathogens Bartonella Leptospira Relapsing Fever, RMSF, Haemophilus other Rickettsia, Babesia, Schistosoma (Roundworms) Klebsiella Yersinia (Schistosomiasis) Bordatella Spiral Anaplasma, Ehrlichia Enterobius (Pinworm) Proteus Coxiella Clonorchis & Fasciola Legionella Campylobacter Intracellular Lice (pediculosis) Trichuris (Whipworm) Serratia Chlamydophila (Liver Flukes) Helicobacter Chlamydia Vectors of: Epidemic typhus, Ascaris (Giant worm) Enterobacter psittaci Paragonimus (Lung Fluke) Trench Fever Ancylostoma & Necator Opportunistic Rickettsia Chlamydophila Mites (scabies) (Hookworm) Pseudomonas Ehrlichia Rickettsia Coxiella Vectors of: Scrub typhus, Cestodes (Tapeworms) Strongyloides (Strongy) Anaplasma Rickettsialpox Enteric pathogens Legionella Taenia saginata Toxocara (Dog Ascaris) Comma Borrelia Mosquitoes (Beef Tapeworm) Trichinella (Trichinosis) Shigella Leptospira Ehrlichia Vectors of: Malaria, Dengue, Salmonella Vibrio Anaplasma Taenia Solium Onchocerca (River Anaerobic Chikungunya, West Nile, (Pig Tapeworm) Yersinia Bartonella Blindness) Yellow Fever Diphyllobothrium Loa Loa (Eye Worm) Bacteroides Brucella Fleas Diplococci (Fish Tapeworm) Wuchereria & Brugia Prevotella Francisella Vectors of: Cat-scratch fever, Neisseria Echinococcus (Elephantiasis) Fusobacterium Shigella Murine typhus, Bubonic Moraxella (Dog Tapeworm) Salmonella plague, Tularemia Anatomical Location of Viral Syndromes URT Nasal Cavity Nasopharynx Oropharynx Larynx 6 airway Pathogenesis mucus goblet cell respiratory epithelium blood vessel smooth muscle 8 airway Pathogenesis mucus goblet cell respiratory epithelium blood vessel smooth muscle 8 Pathogenesis Attach through receptor mediated endocytosis Cellular and tissue Tropism Replicate rapidly in cytosol (RNA viruses) 9 Pathogenesis Local spread of virus stimulation to epithelial cells of mucus production Innate immune and sensing of PAMPs release Interferon, cytokines & chemokines Recruitment of inflammatory cells extravasation 10 Increase in Mucus & airway mucus debris Death of epithelial cells by lysis and exit (non-enveloped viruses) Swelling Increased vascular permeability & inflammatory cell infiltration 11 Mucus & debris normal Swelling 12 Anatomical Location of Viral Syndromes Rhinitis Rhinovirus URT Common Cold Corona Virus Nasal Cavity Nasopharynx Oropharynx Larynx 13 Anatomical Location of Viral Syndromes Rhinitis Rhinovirus URT Common Cold Corona Virus Nasal Cavity Nasopharynx Oropharynx Larynx 13 Rhinovirus & Coronavirus Clinical Manifestations • Incubation period, 2 to 3 days • Mild symptoms for 5 to 7 days • Fever & systemic symptoms are not common • May cause exacerbation of chronic lung disease • More severe in smokers, elderly • Immunocompromised may develop pneumonia 14 Rhinovirus & Coronavirus are RNA viruses Virus II (+) DNA III I (+/-) DNA (+/-) DNA (+/-) RNA VII IV (+/-) gapped (+/-) DNA (+) RNA DNA mRNA (+/-) DNA (-) RNA V (-) DNA PROTEIN (+) RNA VI 15 Rhinovirus & Coronavirus are RNA viruses Virus II (+) DNA III I (+/-) DNA (+/-) DNA (+/-) RNA VII IV (+/-) gapped (+/-) DNA (+) RNA DNA mRNA (+/-) DNA (-) RNA V (-) DNA PROTEIN (+) RNA VI 15 Rhinovirus & Coronavirus Viral Characteristics >100 serotypes at least 6 serogroups naked capsid enveloped Picornaviridae Coronaviridae Poliovirus Enteroviruses SARS Coxackievirus MERS Hepatitis A 16 Coronavirus SARS Global Mortality Deaths Cases 17 Coronavirus SARS Global Mortality Deaths Cases 17 Coronavirus MERS Global Cases 18 Coronavirus MERS Global Cases 18 Anatomical Location of Viral Syndromes Rhinitis Rhinovirus URT Common Cold Corona Virus Nasal Cavity Nasopharynx Pharyngitis Adenovirus Sore Throat Oropharynx Parainfluenza Larynx Laryngitis 19 Adenovirus Clinical Manifestations Typical clinical manifestations • Acute febrile pharyngitis • Pharyngoconjunctival fever • Can be deadly in immunocompromised hosts 20 Adenovirus Viral Characteristics • Double-stranded DNA virus >50 serotypes naked capsid Adenoviridae none 21 Anatomical Location of Viral Syndromes Rhinitis Rhinovirus URT Common Cold Corona Virus Nasal Cavity Nasopharynx Pharyngitis Adenovirus Sore Throat Oropharynx Parainfluenza Larynx Laryngitis 22 Anatomical Location of Viral Syndromes Laryngotracheo- LRT bronchitis Parainfluenza Croup Trachea Bronchi Bronchioles Lung 23 Parainfluenza virus Clinical Manifestations Croup is distinctive • Barking cough with inspiratory stridor • Fever and hoarseness common • Often improves with exposure to cold air or steam • Common in Fall months (Type 1) 24 Subglottic Stenosis Steeple