Upper and Lower Respiratory Tract Infections Meral SÖNMEZOĞLU, MD Yeditepe UniversityHospital AssociateProfessor of Department of InfectiousDiseasesandMicrobiology
Infections of the Respiratory tract • Most common entry point for infections • Upper respiratory tract • nose, nasal cavity, sinuses, mouth, throat • Lower respiratory tract • Trachea, bronchi, bronchioles, and alveoli in the lungs
Upper Respiratory Infections • Common Cold/ Influenza • Pharyngitis, tonsillitis • Acute sinusitis • Acute laryngitis • Acute laryngotracheobronchitis (Croup) • Otitis media, otitis externa, mastoitidis
Bacterial causes of URIs • Streptococcus pyogenes (group A ßhemolytic) • Group C streptococci • Haemophylus influenza • Moraxella catarrhalis • Staphylococcus aureus • Klebsiella pneumoniae • Haemophylus parainfluenzae • Mycoplasma pneumoniae • Chlamydia pneumoniae
Viral causes of URIs • Rhinovirus (100 types and 1 subtype) • Coronavirus (>3 types) • Parainfluenza virus • Respiratory syncytial virus • İnfluenza virus • Adenovirus (type 3,4,7,14,21) • Coxsackievirus A (type 2,4-6,8,10) • Epstein Barr virus • Cytomegalovirus • HIV-1
Clinical characteristics of “common cold” • Incubation period 12-72 hrs • Cardinal symptoms: • Nasal discharges • Nasal obstuctions • Sneezing • Sore and scratchy throat • Cough • Slight fever • Duration 1 week, self limited
Diagnosis • Typical and easy • Differential diagnosis; • -hay fever • -vasomotor rhinitis • Major challenge is to distinguish the uncomplicated cold from secondary bacterial sinusitis and otitismedia
Treatment • First generation antihistaminics • Nonsteroidal anti-inflammatory drugs • Sore throat reliefs with warm saline gargles and topical anesthetics • Oseltamivir?
Prevention • Isolation of the patients for first days • Influenza vaccines
Respiratory Syncytial Virus • Enveloped (membrane) RNA virus • Spread by respiratory droplets • Community outbreaks in late fall to spring • Upper respiratory tract infection – epithelial cells • May be fatal in infants
Influenza Virus An enveloped RNA virus Structure
Influenza Virus • New human strains every year • Mutations • Pandemic strains • Genetic Recombinant Viruses • 1957 Asian Flu H2N2 • 1968 Hong Kong Flu H3N2 • 1977 Russian Flu H1N1 • Bird Flu • Directly from birds • ?? H5N1
‘H’ and ‘N’ Flu Glycoproteins • H – Hemagglutinin • Specific parts bind to host • cells of the respiratory mucosa • Different parts are • recognized by the host antibodies • Subject to changes • N - Neuraminidase • Breaks down protective • mucous coating • Assist in viral release
Influenza • Epidemics and pandemics, mostly in winter • Upper respiratory tract infection – epithelial cells • Multivalent killed virus vaccine with strains from the previous year (Grown in embryonated eggs) • Bird flu (H5N1) pandemic in birds
Pathogenesis of Influenza • Influenza can be transmitted through small or large particle • aerosols or through contact with contaminated surfaces • If not neutralized by mucosal antibodies, virus attacks respiratory tract epithelium • Infection of respiratory epithelial cells leads to cellular dysfunction, viral replication, and release of viral progeny • Release of inflammatory mediators contributes tosystemic manifestations of disease Bridges CB et al. Clin Infect Dis. 2003;37:1094-101. Heikkinen T et al. Lancet. 2003;361:51-9.
Clinical Features of Influenza • Sudden onset of symptoms, persist for 7+ days • Incubation period: 1-4 days, average 2 days • Infectious period of wild type virus: • Adults shed virus typically from 1 day before through 5 days after onset of symptoms • Children shed higher titers for a longer duration than adults ACIP. MMWR. 2004,53(RR06)1-40. Kavet J. Am J Public Health. 1977;67:1063-70. Frank AL et al. J Infect Dis. 1981;144:433-441. Hayden FG et al. JAMA. 1999;282:1240-6.
Influenza Manifestations & Complications Loughlin J et al. Pharmocoeconomics. 2003;21:273-283. Treanor JJ. Influenza virus. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 5th ed. Philadelphia, PA: Churchill Livingstone; 2000:1823-1849. ACIP. MMWR 2004;53 (RR06):1-40.
Patient Groups at Risk for Complications • Increased risk of influenza complications among: • Children <2 years • Children and adolescents receiving long-term aspirin therapy • Children and adults with chronic conditions • Chronic pulmonary, metabolic, or CV disorders • Renal dysfunction • Hemoglobinopathies • Immunosuppression, including HIV infection • Pregnant women • Residents of chronic care facilities • Persons 65 years old • ACIP. MMWR. 2004;53(RR06):1-40.
Pulmonary: Primary influenza viral pneumonia Secondary bacterial pneumonia Croup Asthma, COPD,* bronchitis, cystic fibrosis exacerbation Increased severity of influenza in HIV patients * Chronic obstructive pulmonary disease Non-Pulmonary: Myositis Cardiac complications Toxic shock syndrome Guillain-Barré syndrome Transverse myelitis Encephalitis Reye syndrome Complications
Influenza Diagnostic Testing • Rapid Antigen (EIA) • NP aspirates and swabs only • Detects Influenza A/B nucleoproteins • 1 hour TAT, batched on the hour • Viral Culture (Shell Vial) • Upper and lower respiratory specimens • Detects Influenza A/B, Parainfluenza 1/2/3, Adenovirus and RSV • 24-72 hour TAT • Real-time RT-PCR • Upper and lower respiratory specimens • Detects Influenza A matrix gene • Influenza B validation in progress • 24 hour TAT Increase in Sensitivity
Treatment • Rest, liquids, anti-febrile agents (no aspirin for ages 6mths-18yrs) • Be aware of complications and treat appropriately • Oseltamivir for patients at risk
Sinusitis — facts and figures Definition:–infection of frontal, ethmoidal or maxillary sinuses Symptoms:– facial pain, headache, nasal discharge, fever Prevalence:– 31.2 million cases per year in the USA – 16 million outpatient visits Complications:– permanent mucosal damage and chronic sinusitis – rarely, optic neuritis, subdural abscess and meningitis Schwartz. Nurse Pract 1994;19:58–63
Etiology of acute sinusitis Streptococci8% S. aureus 6% Staphylococci7% M. catarrhalis 1% Anaerobes7% Other bacteria5% S. pneumoniae34% H. influenzae35% Total percentages greater than 100% because of multiple organisms Willett et al. J Gen Intern Med 1994;9:38–45
Sinusitis • Acute sinusitis ; • into three main syndromes: • acute, • subacute • chronic • In young adults, acute sinusitis is responsible for 4.6% of physician consultations
RV in Acute Sinusitis • Sinusitis is an extremely common part of the common cold syndrome • RV has been detected in 50% of adult patients with sinusitis by RT-PCR of maxillary sinus brushings or nasal swabs1 • Frequency of association of RV infection with sinusitis suggests the common cold could be considered a rhinosinusitis2 • Pitkäranta A et al. J Clin Microbial. 1997;35:1791. • Gwaltney JM Jr. Clin Infect Dis. 1996;23:1209.
Acute pharyngitis/tonsillitis — facts and figures Definition: – inflammation of the pharynx or tonsils Symptoms: – pharyngeal pain, dysphagia and fever Epidemiology: – 1% physician visits/year – most common childhood bacterial infectiona Complications: – acute rheumatic fever and glomerulonephritisa Gwaltney. In: Principles and Practicesof Infectious Disease 1990;43:493–8 aStreptococcal pharyngitis
Etiology of pharyngitis Coronavirus(5%) Rhinovirus(20%) Adenovirus(5%) Other bacteria/viruses(7%) S. pyogenes(15–30%) Unknown(40%) Gwaltney. In: Principles and Practices of Infectious Disease 1990;43:493–8
Acute otitis media — facts and figures Definition: – infection of the middle ear leading to accumulation of fluid and inflammation of the tympanic membrane Symptoms: – cough, fever, irritability, earache Epidemiology: – 24.5 million physician visits per year – majority of cases occur in children <2 years – most frequent indication for antimicrobial treatment in children in the USA Complications: – loss of hearing Garau et al. Clin Microbiol Infect 1998;4:51–8 Klein. Clin Infect Dis 1994;19:823–33
Acute otitis media — etiology M. catarrhalis 14% H. influenzae 23% S. pneumoniae 35% Unknown 16% S. pyogenes 3% S. aureus 1% Others 32% 2807 effusions from patients in the USA 1980–1989 Total percentages greater than 100% because of multiple organisms Bluestone et al. Paediatr Infect Dis J 1992;11:7–11
Acute Bronchitis Inflammation of the bronchial respiratory mucosa leading to productive cough.
Acute Bronchitis • Etiology: A)Viral B) Bacterial (Bordetella pertussis, Mycoplasma pneumoniae, and Chlamydia pneumoniae) • Diagnosis: Clinical • S/S: Productive cough, rarely fever or tachypnea.
Treatment Symptomatic If cough persists for more than 10 days: Azithro x 5 days OR Clarithro x 7 days
Pneumonia Bacterial, viral or fungal infection can cause Inflammation of the lung with fluid filled alveoli
Frequency of causative organisms of community-acquired pneumonia (CAP) in Europe. Welte T et al. Thorax 2012;67:71-79
Frequency of Isolation of Causative Organisms of CAP in Europe by Country
Protective Mechanisms Normal flora: Commensal organisms • Limited to the upper tract • Mostly Gram positive or anaeorbic • Microbial antagonist (competition)
Defense Mechanisms • 80% of cells lining central airways are ciliated, pseudostratified, columnar epithelial cells • Each ciliated cell contains about 200 cilia that beat in coordinated waves about 1000x/minute • So the lower respiratory tract is normally sterile
Protective Mechanisms Clearance of particles and organisms from the respiratory tract Cilia and microvilli move particles up to the throat where they are swallowed. Alveolar macrophages migrate and engulf particles and bacteria in the alveoli deep in the lungs.
Other Protective Mechanisms • Nasal hair, nasal turbinates • Mucus • Involuntary responses (coughing) • Secretory IgA • Immune cells
First cause of death in the United States from infectious disease is: A. Meningitis B. Pneumonia C. Gastroenteritis D. Urinary Tract Infections E. Toe fungus