Viral Lower Respiratory Tract Infections

Transcription

1

2 Viral Lower 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

3 Learning Objectives Recognize the clinical characteristics of bronchitis and bronchiolitis Describe how the clinical characteristics of bronchiolitis relates to the pathogenesis of RSV infection. Discuss potential complications, management and prevention strategies for RSV-induced bronchiolitis. Compare the clinical manifestations of RSV to that of human metapneumovirus 3

4 Major Human Pathogens Gram positive Bacteria Cocci Staphylococcus Streptococcus Enterococcus No cell wall Pleomorphic Mycoplasma Rods Listeria Bacillus Clostridium Corynebacterium Gardnerella Propionibacterium Branching Actinomyces Nocardia Acid Fast Bacilli Mycobacterium tuberculosis Mycobacterium leprae Non-tuberculous Mycobacteria Gram negative Bacteria Rods Enteric flora E. coli Klebsiella Proteus Serratia Enterobacter Enteric pathogens Shigella Salmonella Yersinia Respiratory Pathogens Haemophilus Bordatella Spiral Legionella Campylobacter Helicobacter Opportunistic Pseudomonas Anaerobic Bacteroides Prevotella Fusobacterium Comma Vibrio Diplococci Neisseria Moraxella Zoonotic Brucella Francisella Campylobacter Pasteurella Bartonella Yersinia Coxiella Chlamydophila psittaci Rickettsia Ehrlichia Anaplasma Borrelia Leptospira RNA Rhinovirus Coxsackie Enteroviruses Poliovirus Rotavirus Norovirus Hepatitis A Hepatitis C HIV HTLV-1 Measles Mumps Rubella Spirochaetes Treponema Borrelia Leptospira Intracellular Chlamydia Chlamydophila Rickettsia Coxiella Legionella Ehrlichia Anaplasma Bartonella Brucella Francisella Shigella Salmonella Viruses Influenza A, B Parainfluenza RSV Human metapneumovirus Coronavirus (MERS, SARS) Ebola Rabies Vector borne West Nile Dengue Chickengunya Yellow Fever DNA Adenovirus Herpes simplex Varicella zoster Cytomegalovirus Epstein Barr virus HHV6, HHV7, HHV8 Smallpox Molluscum contagiosum Hepatitis B Parvovirus Human papillomavirus BK polyomavirus Arthropods Ticks Vectors of: Lyme borreliosis, Relapsing Fever, RMSF, other Rickettsia, Babesia, Anaplasma, Ehrlichia Lice (pediculosis) Vectors of: Epidemic typhus, Trench Fever Mites (scabies) Vectors of: Scrub typhus, Rickettsialpox Mosquitoes Vectors of: Malaria, Dengue, Chikungunya, West Nile, Yellow Fever Fleas Vectors of: Cat-scratch fever, Murine typhus, Bubonic plague, Tularemia Fungi Mold Yeast Dimorphic Aspergillus Candida Mucor Coccidioides Cryptococcus Rhizopus Histoplasmosis Pneumocystis Fusarium Blastomyces Paracoccidioides Malassezia Sporothrix Microsporidia Dermatophytes Microsporum, Epidermophytum Trichophytum Helminths Protozoa GI/GU Entamoeba Giardia Cryptosporidium Trichomonas Trematodes (Flukes) Schistosoma (Schistosomiasis) Clonorchis & Fasciola (Liver Flukes) Paragonimus (Lung Fluke) Cestodes (Tapeworms) Taenia saginata (Beef Tapeworm) Taenia Solium (Pig Tapeworm) Diphyllobothrium (Fish Tapeworm) Echinococcus (Dog Tapeworm) Blood Plasmodium Babesia Tissue Trypanosoma Leishmania Toxoplasma Nematodes (Roundworms) Enterobius (Pinworm) Trichuris (Whipworm) Ascaris (Giant worm) Ancylostoma & Necator (Hookworm) Strongyloides (Strongy) Toxocara (Dog Ascaris) Trichinella (Trichinosis) Onchocerca (River Blindness) Loa Loa (Eye Worm) Wuchereria & Brugia (Elephantiasis)

5 RNA Rhinovirus Coxsackie Enteroviruses Poliovirus Rotavirus Norovirus Hepatitis A Hepatitis C HIV HTLV-1 Measles Mumps Rubella Viruses Influenza A, B Parainfluenza RSV Human metapneumovirus Coronavirus (MERS, SARS) Ebola Rabies Vector borne West Nile Dengue Chickengunya Yellow Fever DNA Adenovirus Herpes simplex Varicella zoster Cytomegalovirus Epstein Barr virus HHV6, HHV7, HHV8 Smallpox Molluscum contagiosum Hepatitis B Parvovirus Human papillomavirus BK polyomavirus

6 Bronchitis and Bronchiolitis URT Nasal Cavity Nasopharynx Oropharynx Larynx LRT Trachea Bronchi Bronchioles Lung Rhinitis Common Cold Pharyngitis Sore Throat Laryngitis Laryngotracheobronchitis Croup Bronchitis Bronchiolitis Rhinovirus Corona Virus Adenovirus Parainfluenza Parainfluenza Parainfluenza, Influenza Adenovirus, Metapneumovirus RSV, Corona RSV, Influenza, Metapneumovirus Adenovirus Pneumonia All 6

7 Bronchitis clinical manifestations & pathogenesis Productive cough for to days 7

8 Bronchitis clinical manifestations & pathogenesis Productive cough for to days Purulent sputum - 50% of patients; does not mean bacterial infection Predominantly viral; few bacterial causes Fever is unusual 7

9 Bronchiolitis LRT Trachea Bronchi Bronchioles Lung Bronchitis Bronchiolitis Parainfluenza, Influenza Adenovirus, Metapneumovirus RSV, Corona RSV, Influenza, Metapneumovirus Adenovirus Pneumonia All 8

10 Bronchiolitis Clinical Manifestations Affects mostly infants and young children 4-6 day incubation period most common in Winter Begins with URI symptoms and fever Progress to tachypnea, cough, respiratory distress with retractions and wheezing 9

11 RSV- Pathogenesis Mucus & debris RSV infects respiratory epithelial cells Innate immune sensors detect PAMPs and produce interferon and other cytokines and chemokines Inflammatory cells recruited Increased vascular flow, permeability and increased mucus production Apoptosis and sloughing of epithelial cells Swelling 11

12 Bronchiolitis Pathogenesis & Clinical Manifestations Outpouring of mucus & inflammatory cells leads to Small airway plugging with air trapping Impeded gas exchange 12

13 Bronchiolitis Complications Respiratory failure Apnea in newborns and/or premature infants Increased severity in: newborns and the elderly congenital heart disease chronic lung disease immune compromised 13

14 Bronchiolitis Treatment Assess the severity and progression Determine risks factors Treatment is supportive Drugs to overcome airway obstruction? 14

15 RSV Respiratory Syncytial Virus F G 1 serotype RSV is the most important viral pathogen during the first year of life. Two important surface proteins (F-fusion & G-attachment) Syncy'um enveloped Paramyxoviridae Parainfluenza Metapneumovirus Mumps Measles Hendra Nipah 15

16 RSV- Mechanisms of Immune evasion Protective immunity is incomplete and short-lived G-protein is heavily glycosylated G-protein can be produced in a soluble form and act as a decoy RSV can infect dendritic cells and reduce antigen presentation to T-cells F G 17

17 RSV- Mechanisms of Immune evasion Protective immunity is incomplete and short-lived G-protein is heavily glycosylated G-protein can be produced in a soluble form and act as a decoy RSV can infect dendritic cells and reduce antigen presentation to T-cells F G 17

18 RSV- Mechanisms of Immune evasion Protective immunity is incomplete and short-lived G-protein is heavily glycosylated G-protein can be produced in a soluble form and act as a decoy RSV can infect dendritic cells and reduce antigen presentation to T-cells F G G 17

19 Host Factors Involved in RSV disease After age 2 most children do not develop severe disease from RSV Smaller airways and less respiratory capacity and reserve Immature infant immune system Innate and adaptive responses may be deficient compared to adults 18

20 Host Factors Involved in RSV disease Immunopathology recurrent wheezing in some infants after RSV association with asthma later in life 19

21 Prevention of RSV disease No vaccine available Passive immunity Palivizumab- Monoclonal Antibody against F-Protein Used in children < 2 years with cyanotic congenital heart disease, chronic lung disease, or prematurity < 35 weeks F G 20

22 Human Metapneumovirus One serotype Similar structure to RSV Mimics RSV epidemiology & clinical disease 1 serotype enveloped Paramyxoviridae Parainfluenza RSV Mumps Measles Hendra Nipah 21

23 Bronchitis and Bronchiolitis URT Nasal Cavity Nasopharynx Oropharynx Larynx LRT Trachea Bronchi Bronchioles Lung Rhinitis Common Cold Pharyngitis Sore Throat Laryngitis Laryngotracheobronchitis Croup Bronchitis Bronchiolitis Rhinovirus Corona Virus Adenovirus Parainfluenza Parainfluenza Parainfluenza, Influenza Adenovirus, Metapneumovirus RSV, Corona RSV, Influenza, Metapneumovirus Adenovirus Pneumonia All 22

24 Credits: Viral Lower Respiratory Tract Infections Slide 6: Respiratory Tract diagram modified from: Slide 7: Coughing adult. Patient Education ExitCare Patient Information 2014 ExitCare, LLC. Slide 9: Infant recovering from RSV bronchiolitis with nasal canula O2 shows tachypnea and retractions. Edited from: Slide 14: Ventilation mask diagram. Karlowicz, M. Gary, MD, FAAP, Karotkin, Edward H., MD, FAAP,Goldsmith, Jay P., MD, FAAP - Assisted Ventilation of the Neonate, Copyright 2011, 2003, 1996, 1988, 1981 by Saunders, an imprint of Elsevier Inc. Slide 15: RSV syncytium in cell culture. From: Tian J et al. J Gen Virol 2013;94: Slide 19: Asthma inhaler Patient Education ExitCare Patient Information 2014 ExitCare, LLC 23