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Upper Respiratory Tract Infections Dr Meral Sönmezoğlu Yeditepe University Hospital Infectious Diseases Major sites of community-acquired respiratory tract infections Frontal sinus Sinusitis Maxillary sinus Pharyngitis Pneumonia Bronchitis 3 Upper Respiratory Infections • • • • • Common Cold Pharyngitis Acute laryngitis Acute laryngotracheobronchitis (Croup) Otitis media, otitis externa, mastoitidis Respiratory tract infections — a major cause of mortality Age (years) Death from respiratory infections in the developed world in 1990 0–4 5–14 15–29 30–44 45–59 60–69 70+ 0 50 100 150 200 250 300 Estimated deaths (x 103) Murray & Lopez. Bull World Health Organ 1994;72:447–80 Incidence of community-acquired lower respiratory tract infection increases with age Age (years) 16–19 20–29 30–39 40–49 50–59 60–69 70–79 0 20 40 60 80 100 120 140 Cases per 1000 population/year MacFarlane et al. Lancet 1993;341:511–14 Impact of URIs • Recognized for the last century as the most common infectious illness in humans • Terminology has varied – Common respiratory infection – Common cold – Rhinosinusitis • Rhinoviruses (RVs) cause a majority of these infections Monto AS et al. Clin Ther. 2001;1615. Seasonality of Respiratory Agents: Proportion Isolated in Each Calendar Month During 6 Years of Tecumseh, Michigan, Study 30 RV Parainfluenza viruses Respiratory syncytial virus (RSV) Influenza virus Percent 25 20 15 10 5 0 30 Percent 25 20 15 10 5 0 Jan Apr Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jan Apr Sep Oct Nov Dec Jan Feb Mar Apr May Jun Reprinted from Br J Prev Soc Med, 1977;31:101-108, with permission from the BMJ Publishing Group. Transmission of Respiratory Viruses • Transmission of viruses differs • Influenza – Airborne transmission1 – Widespread outbreaks • RVs – Closer contact required – Aerosol and direct2,3 – Households and schools are sites of transmission4 1. Goldman DA. Pediatr Infect Dis J. 2000;19(10 suppl):S97. 2. Gwaltney JM Jr, Hendley JO. Am J Epidemiol. 1982;116:828. 3. Dick EC et al. J Infect Dis. 1987;156:442. 4. Gwaltney JM Jr. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 5th ed. Philadelphia: Churchill Livingstone; 2000:1940. Mucosal invasion of pathogens Clinical Features and Duration of Illness in Adults with RV Colds (n=276, RV confirmed by PCR or culture) Clinical feature RV % positive First symptom (% of subjects) Sore throat Stuffy nose Runny nose Sneezing 39 17 17 8 Most bothersome symptom (% of subjects) Runny nose Stuffy nose Sore throat Malaise 36 20 19 10 Median duration of symptoms (days) Cold episode Sleep disturbance Interference with daily activities 11 4 7 Adapted with permission from Arruda E et al. J Clin Microbiol. 1997;35:2864. Differentials Symptoms Allergy URI Rare (conjunctivitis may occur with adenovirus) Common Common Very common Itchy, watery eyes Common Nasal discharge Nasal congestion Sneezing Common Common Very common Sore throat Sometimes (postnasal drip) Very common Cough Sometimes Headache Uncommon Fever Never Rare in adults, possible in children Malaise Sometimes Sometimes Fatigue, weakness Sometimes Sometimes Muscle pain Never Slight Common (mild to moderate, hacking) Rare Influenza Soreness behind eyes, sometimes conjunctivitis Common Sometimes Sometimes Sometimes Common (dry cough, can be severe) Common Very common (100-102°F (or higher in young children), lasting 3–4 days; may have chills) Very common Very common, can last for weeks, extreme exhaustion early in course Very common, often severe 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 Childhood etiology of URTI • A respiratory virus was found in 62% (RSV 29%, rhinovirus 24%, parainfluenza viruses 10%, adenovirus 7%, influenza viruses 4%, other viruses 8%) • Bacterial agent in 53% (Streptococcus pneumoniae, 37%, Haemophilus influenzae 9%, Mycoplasma pneumoniae, 7%, Moraxella catarrhalis 4%, Chlamydia pneumoniae 3%, other bacteria 2%). • In 30% of cases there was evidence of a mixed viral/bacterial infection, viral infection alone was detected in 32% and bacterial infection alone in 22% of patients Thorax 2002;57:438–441 Etiology of common cold JCM Feb. 1998, p. 539–542 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 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 Streptococci S. aureus 8% Staphylococci 6% M. catarrhalis 7% 1% Anaerobes 7% S. pneumoniae 34% Other bacteria 5% H. influenzae 35% 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 1. Pitkäranta A et al. J Clin Microbial. 1997;35:1791. 2. Gwaltney JM Jr. Clin Infect Dis. 1996;23:1209. X-ray of Sinuses 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 aStreptococcal pharyngitis Gwaltney. In: Principles and Practices of Infectious Disease 1990;43:493–8 Strep Throat • Fever • Tonsillitis • Enlarged lymph nodes • Middle-ear infection Acute streptococcal pharyngitis /tonsillitis Etiology of pharyngitis Coronavirus (5%) Adenovirus (5%) S. pyogenes (15–30%) Rhinovirus (20%) Other bacteria/viruses (7%) Unknown (40%) Gwaltney. In: Principles and Practices of Infectious Disease 1990;43:493–8 Pharyngitis Diagnosis • B-Haemolytic colonies of Group A Streptococcus from a throat swab 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 Infected Middle Ear (otitis media) Acute otitis media — etiology M. catarrhalis 14% H. influenzae 23% S. pneumoniae 35% Unknown 16% Others 32% S. pyogenes 3% S. aureus 1% 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 Epiglottis • Definition:Inflammination of the epiglottis due to infection • Epidemiology:usually occurs in the winter months • Causative Organisms:H.Influenzae( now rare), S.pyogenes, Pneumococcus, Staphylococcus aureus Epiglottis Clinical Presentation • In children because of the small airway may obstruct breathing and symptoms of adults • In adults fever, pain on swallowing, sore throat, cough sometimes with purulent secretions Epiglottis Diagnosis • Clinical presentation • Lateral X-ray • Blood Cultures/Respiratory Secretions for Culture Epiglottis Clinical Management • Maintain airway in children may require tracheostomy • ( trachestomy set should be at bedside) • Cefotaxime I/V Haemophilus Influenzae Culture Influenza Virus An enveloped RNA virus Structure ‘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 H1N1 2009 (Swine Flu) 46 Influenza A/California/7/2009 (H1N1) 47 Influenza Disease Burden in an Average Year Deaths 25,000 - 72,000 Hospitalizations 114,000 - 257,500 Physician visits ~ 25 million Infections and illnesses 50 - 60 million Thompson WW et al. JAMA. 2003;289:179-86. Couch RB. Ann Intern Med. 2000;133:992-8. Patriarca PA. JAMA. 1999;282:75-7. ACIP. MMWR. 2004;53(RR06):1-40. INFLUENZA: BIOLOGY & IMPACT • Single-stranded, enveloped, RNA virus (orthomyxoviridae family) • Influenza A – Potentially severe illness; epidemic and pandemics – Rapidly changing • Influenza B – Usually less severe illness; may cause epidemics – More uniform • Influenza C – Usually mild or asymptomatic illness INFLUENZA: BIOLOGY & IMPACT • Impact – 25-50 million people contract influenza annually representing and attack rate of 10-20%. – ~115,000 hospitalizations per year – ~35,000 (20,000 – 40,000) deaths per year • Causes respiratory tract disease – Sudden onset – More severe pneumonia during pregnancy • No carrier state (but inapparent illness may occur) INFLUENZA: EPIDEMIOLOGY • • • • Geographic distribution – global Reservoir: Humans, swine, birds Incubation - 1 to 5 days; usually 2 days Transmission – Droplet (airborne?) route – Direct contact • Communicability 1. – 1 to 2 days before onset of symptoms to 4 to 5 days post-onset – Attack rates: Up to 60% Influenza Activity Can Peak From December Through May Month of peak influenza activity during influenza seasons in the United States, 1976–2002 # of Years with Peak Influenza Activity 12 11 10 8 6 6 4 4 3 2 1 1 APR MAY 0 DEC JAN FEB www.cdc.gov/nip/publications/pink/flu.pdf. MAR Pandemi Structure of the Influenza Virus Hemagglutinin (HA) Neuraminidase (NA) M2 Nucleoprotein (NP) M1 Polymerase (P) Proteins Adapted from: Hayden FG et al. Clin Virol. 1997:911-42. Viral Nomenclature Type of Nuclear Material Hemagglutinin Neuraminidase A / Sydney / 184 / 93 (H3N2) Virus type 1. Geographic Strain Year of origin number isolation Virus subtype CDC. Atkinson W, et al. Chapter 13: Influenza. In: Epidemiology and Prevention of Vaccine-Preventable Diseases, 4th ed. Department of Health and Human Services, Public Health Service, 1998, 220 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 to systemic 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. Clinical Manifestations by Age Group Influenza Sign/Symptom Cough (nonproductive) Fever Myalgia Headache Malaise Sore throat Rhinitis/nasal congestion Abdominal pain/diarrhea Nausea/vomiting Children Adults Elderly ++ +++ + ++ + + ++ + ++ ++++ +++ + ++ + ++ ++ – – +++ + + + +++ + + + + Monto AS et al. Arch Intern Med. 2000;160:3243-47. Cox NJ et al. Lancet. 1999;354:1277-82. ++++ Most frequent sign/symptom; + Least frequent; – Infrequent Influenza Manifestations & Complications Frequent Rare Exacerbations of underlying disease Children Adults Sinusitis, bronchitis, bronchiolitis, pneumonia, croup, acute otitis media Encephalopathy, myositis, rhabdomyolysis, myocarditis, pericarditis, Reye syndrome, sepsis-like syndrome Cardiovascular, diabetes, asthma, cystic fibrosis Primary viral pneumonia, secondary bacterial pneumonia, sinusitis, bronchitis Myositis, rhabdomyolysis, myocarditis, pericarditis Cardiovascular, diabetes, asthma, COPD 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. Complications Pulmonary: Non-Pulmonary: l Primary influenza viral pneumonia l Secondary bacterial pneumonia l Croup l Asthma, COPD,* bronchitis, cystic fibrosis exacerbation l Increased severity of influenza in HIV patients l l l l l l l * Chronic obstructive pulmonary disease Myositis Cardiac complications Toxic shock syndrome Guillain-Barré syndrome Transverse myelitis Encephalitis Reye syndrome Influenza Diagnostic Testing • Rapid Antigen (EIA) • 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 – NP aspirates and swabs only – Detects Influenza A/B nucleoproteins – 1 hour TAT, batched on the hour INFLUENZA VACCINE: INDICATIONS • • • • • • • • • • Healthcare providers Persons >65 years of age Residents of extended care facilities of any age Adults and children with chronic cardio-respiratory illnesses Adults and children with chronic metabolic disorders, immune deficiencies, or immunosuppression Children (6 mo–18 yr) receiving aspirin (risk for Reye syndrome) Out-of-home caregivers and household contacts of children <6 mo Women who will be pregnant during influenza season Children aged 6-23 months People who want to avoid influenza INFLUENZA VACCINE (Inactivated): CONTRAINDICATIONS • Hypersensitivity to eggs or vaccine components • Acute febrile illness (postpone vaccine) • Active neurologic disorder characterized by changing neurologic findings. Previous Guillain-Barre or other neurologic illnesses related to previously administered vaccine • Pregnancy or breastfeeding NOT a contraindication Avrupa Birliği e-cdc e- cdc Türkiye Sağlık Bakanlığı Açıklaması • Aralık son haftasından 12.01.2016 a kadar • 2905 solunum semptomu olan hastadan alınan örneklerden 463’ünde İnfluenza A H1N1 virüsü tespit edildi • 1261 örnekte bir solunum yolu virüsü tespit edilmiştir. Bunlardan 595’inde Rhino, RSV gibi diğer solunum yolu virüsleri, 463’ünde İnfluenza A H1N1, 134’ünde İnfluenza A H3N2 ve 38’inde İnfluenza B Virüs Rhino ve diğer virüsler İnfluenza A H1N1 İnfluenza A H3N2 İnfluenza B Toplam Sayı % 595 49 463 37 134 11 38 3 1261 Virüsler Influenza A (H1N1) Diğer virüsler Influenza A (H3N2) Influenza B) 78 Şubat 2016 • 3931 Grip Benzeri Hastalık • 3087 Influenza • %70 H1N1 2015-2016 influenza season It is recommended that vaccines for use in the 20152016 influenza season (northern hemisphere winter) contain the following: • - A/California/7/2009 (H1N1)pdm09-like virus; • - A/Switzerland/9715293/2013 (H3N2)-like virus; • - B/Phuket/3073/2013-like virus. It is recommended that quadrivalent vaccines containing two influenza B viruses contain the above three viruses and – a B/Brisbane/60/2008-like virus. REPORTING TUS 2012 Ülkemizde bildirimi zorunlu olan bulaşıcı hastalıklardan bazıları sadece seçilmiş sağlık merkezlerinden bildirilmektedir. Aşağıdakilerden hangisi bu grupta yer alan hastalıklardan biridir? A) Sıtma B) Difteri C) Tifüs D) Tüberküloz E) İnfluenza TUS 2012 Ülkemizde bildirimi zorunlu olan bulaşıcı hastalıklardan bazıları sadece seçilmiş sağlık merkezlerinden bildirilmektedir. Aşağıdakilerden hangisi bu grupta yer alan hastalıklardan biridir? A) Sıtma B) Difteri C) Tifüs D) Tüberküloz E) İnfluenza TUS 2012 I. 38°C’den fazla ateş II. 3 yaşından küçük hasta III. Ağrısız servikal lenfadenopati IV. Konjunktivit V. Eksüdatif tonsillofarenjit Akut tonsillofarenjiti olan bir hastada yukarıdaki bulgulardan hangisinin varlığı, etkenin A grubu beta-hemolitik streptokok olma olasılığını güçlendirir? • A) | ve III • B) l ve V • C) I, ll ve lll • D) II, IIl ve lV • E) II. IIl ve V TUS 2012 • • • • • I. 38°C’den fazla ateş II. 3 yaşından küçük hasta III. Ağrısız servikal lenfadenopati IV. Konjunktivit V. Eksüdatif tonsillofarenjit • Akut tonsillofarenjiti olan bir hastada yukarıdaki bulgulardan hangisinin varlığı, etkenin A grubu betahemolitik streptokok olma olasılığını güçlendirir? • A) | ve III • B) l ve V • C) I, ll ve lll • D) II, IIl ve lV • E) II. IIl ve V TUS 2014 • Tonsillofarenjit sonrası tortikollis,ateş? • – retrofaringeal apse