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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