VIRAL RESPIRATORY TRACT

INFECTIONS AND
ENTEROVIRAL INFECTIONS

Kyiv Medical University

Department of Infectious diseases, Phthisiology and
Pulmonology

MD, PhD, Associate Professor, Viktoriia Potii

 Classification of URTI
Viruses Orthomyxoviridae Common cold
Paramyxoviridae Pharyngitis
Adenoviridae Laryngotra-
Picornaviridae cheobronchitis
Coronaviridae Tracheitis
Metapneumoviridae Bronchitis
Herpesviridae Bronchiolitis
Pneumonia
 Classification of URTI
(continue)
Bacteria Legionella pneumoniae
Pneunonia
Streptococcus spp.
Sts. pneumoniae Bronchitis
Staphilococcus aureus
Neisseria meningitidis
Pharyngitis
Corinebacterium diphtheria Nasopharyngitis
Hemophiles influenzae
Moraxella catarrhalis
Epiglottitis
Bordetella pertussis Tonsillitis
Bordetella parapertussis
Mycobacterium tuberculosum
Mycobacterium avium
Klebsialla pneumonia
Escherichia coli
Pseudomonas aeruginosa
 Classification of URTI
(continue)
Chlamydia Chlamydia Pneumonia
pneumoniae Bronchitis
Chlamydia Pharyngitis
psittaci

Mycoplasma Mycoplasma Pneumonia

pneumoniae Bronchitis
Mycoplasma Pharyngitis
hominis

Rickettsia Coxiella burnetii Pneumonia

 Classification of URTI
(continue)
Helminth Echinococcus Pneumonia
multilocularis
Toxocare canis
Toxoascaris leonine
Larva-migrans-complex
Fungus Candide albicans Pneumonia
Coccidioides immitis
Histoplasma
capsulatum
Protozoa Pneumocyctis carinii Pneumonia
 INFLUENZA
ETIOLOGY
Orthomyxoviridae family
Three antigenic types:
– influenza virus A
– influenza virus B
– influenza virus C
 ETIOLOGY (CONTINUE)
Influenza viruse:
– is spherical particles 80 to 120 nm
– contains a single, segmented RNA genome
– contains the nucleoprotein (NP) antigen
– three polymerase (P) proteins
– has a lipid envelope
– has hemagglutinin (H) and neuraminidase (N)
ETIOLOGY (PICTURE)
ETIOLOGY (PHOTO)
 ETIOLOGY (CONTINUE)
Influenza virus has 15 H and 9 N
subtypes
In humans only H1, H2, H3, and N1,
N2 are associated with disease
 EPIDEMIOLOGY
Influenza A viruses cause:
– epidemics every 2 to 4 years
– pandemics every decade
Influenza B viruses cause:
– localized outbreaks (particularly in schools
and military camps)
– epidemics every 4 to 6 years
Influenza C viruses cause sporadic
diseases
 VIRUS STRUCTURE

Antigenic variation of influenza

A viruses:
–Major variations - antigenic
shifts
–Minor variations - antigenic
drifts
 EPIDEMIOLOGY

In temperate climate epidemics of

influenza occur in the winter months

In the tropics influenza virus

infections occur year-round
 EPIDEMIOLOGY
Influenza is airborne infection:

– contamination by a small-particle
aerosol (particle diameter <10 mm)
is more efficient than by larger
droplets
 PATHOGENESIS
1. Influenza virus enters the human host through
the respiratory tract
2. Viruses replicate in the ciliated columnar
epithelial cells of the upper respiratory tract:
– initial virus replication lasts 4 - 6 h
– viruses release from infected cells
– viruses infect nearby cells
– infected ciliated cells become necrotic and
desquamate
 PATHOGENESIS

3. Viremia and toxaemia

4. Immune response:
– Humoral immunity (specific Ig M, Ig G)
– Secretory immunity (Ig A)
– Cell-mediated immune response:
(antigenspecific and antigen-
nonspecific)
CLINICAL MANIFESTATIONS
Incubation period usually lasts 18 to
36 (up to 3 days)
Sudden onset of disease
High temperature 380 - 410C (100.40
to 105.80F)
Systemic symptoms: chill, fever,
malaise, headache, arthralgia or
myalgia
CLINICAL MANIFESTATIONS
Ocular symptoms: pain on motion of the
eyes, retroorbital pain, photophobia, and
burning or watering of the eyes
Respiratory tract signs:
– stuffy nose
– dry painful troublesome cough with
substernal discomfort
– sore throat
CLINICAL MANIFESTATIONS
Examination:
– face of patient is flushed
– skin is hot and dry
– pharynx is hyperemic and cyanotic (plural petechia)
– in severe cases: tachycardia, epistaxis, nausea,
vomiting, dyspnea, cyanosis and prostration
Duration of disease is 1 week
Cough may persist for 1 to 2 weeks longer
Postinfluenzal asthenia may persist for several
weeks
 COMPLICATIONS
Pneumonia:
– “primary” influenza viral pneumonia
– secondary bacterial pneumonia
– mixed viral and bacterial pneumonia
Sinusitis
Otitis media
Myocarditis, pericarditis
Shock
Neurological disoders: meningitis, encephalitis, myelitis,
and Guillain-Barre syndrome
Exacerbation of chronic obstructive pulmonary disease,
chronic bronchitis and asthma
 LABORATORY FINDINGS
Viral culture (from throat swabs, sputum,
nasopharyngeal washes)
Polymerase chain reaction
Serologic methods (antibody serology
titres must demonstrate a 4-fold rise)
Immunofluorescence method
Culture method
(Chick embryos)
 TREATMENT
Outpatient treatment: bed rest, fluid
hydration, vitamins, antipyretics and
analgesics
Antibiotics should be prescribed for
treatment of bacterial complications or for
prevention of bacterial complications
Antiviral agents: Oseltamivir (Famiflu) and
Zanamivir (Relenza).
 PREVENTION
Oseltamivir and Zanamivir in
prophylactic dose – ½ the acute
treatment dose
Influenza vaccine
People recommended for
immunization:
– elderly individuals
– patients with certain chronic diseases
– health care workers
VIRAL RESPIRATORY TRACT
INFECTIONS
rhinovirus infections
adenovirus infections
parainfluenza virus infections
respiratory syncytial virus
infections
 VIRAL RESPIRATORY TRACT
INFECTIONS (main syndromes)
Rhinitis - Inflammation of the nasal mucosa
Sinusitis - Inflammation of the paranasal
sinuses
Nasopharyngitis (rhinopharyngitis or the
common cold) - Inflammation of the nasal
mucosa, pharynx, and uvula
Pharyngitis - Inflammation of the pharynx,
hypopharynx, and uvula
Tonsillitis - Inflammation of the pharynx, and
tonsils
Epiglottitis - Inflammation of the superior
portion of the larynx and supraglottic area
 VIRAL RESPIRATORY TRACT
INFECTIONS (main syndromes)
Laryngitis - Inflammation of the larynx
Laryngotracheitis - Inflammation of the larynx,
and trachea
Laryngotracheobronchitis (croup) -
Inflammation of the larynx, trachea, and bronchi
Tracheobronchitis - Inflammation of the
trachea and bronchi
Bronchitis - Inflammation of the bronchi
Bronchiolitis - Inflammation of the bronchioles
Pneumonia - Inflammation of the pulmonary
tissue
 VIRAL RESPIRATORY TRACT
INFECTIONS
Rhinoviruses Nasal cavity (rhinitis)

Adenoviruses Oropharings (tonsillitis,

pharyngitis)
Parainfluenza viruses Larynx (laryngitis)

Influenza viruses Trachea (tracheitis,

tracheobronchitis)
Respiratory syncytial Bronchi, bronchiole
viruses (bronchitis, bronchiolitis)
 RINOVIRUS INFECTIONS
ETYOLOGY
Picornaviridae family
Size 15 to 30 nm
Contain a single-stranded RNA
genome
102 distinct serotypes
Optimality condition –the temperature
330 to 340C
 RINOVIRUS INFECTIONS
EPIDEMIOLOGY
Rhinoviruses:
– major cause of the common cold in adults (15
-40%)
– more often occur among infants and young
children
– in temperate climates occur year-round, with
seasonal peaks in early fall and spring
Transmission:
– via respiratory aerosols
– via direct contact with infected secretions
 RINOVIRUS INFECTIONS
CLINICAL MANIFESTATIONS
Incubation period 1 - 2 days
acute onset of disease
rhinorrhea, sneezing, mucous discharge, nasal
congestion
sore throat
systemic symptoms are mild or absent
temperature is normal
duration 4 to 9 days
Rhinovirus infections are mild and self-limited
 ADENOVIRUS INFECTIONS
ETIOLOGY
Mastadenovirus genus
51 serotypes
size 70 - 80 nm in diameter
contain a linear double-stranded DNA genome
Adenovirus infections:
– most frequently in infants and children
– very rarely in adults
Transmission:
– via respiratory aerosols
– by direct inoculation of virus into conjunctival sacs
– by the fecal-oral route
 ADENOVIRUS INFECTIONS
CLASSIFICATION
Clinical syndromes:
– upper respiratory tract infection
– pharyngoconjunctival fever
– pharyngitis
– acute diarrheal illness
– hemorrhagic cystitis
– epidemic keratoconjunctivitis
– pneumonia
 ADENOVIRUS INFECTIONS
CLINICAL MANIFESTATIONS
Acute or gradual onset of disease
Temperature is up to 390C (102,20F)
Sore throat and tenderness swallowing
Cough
Coryza
Regional lymphadenopathy
Pharyngeal edema, injection, hyperaemia
Tonsillar enlargement with little or no exudate
 ADENOVIRUS INFECTIONS
CLINICAL MANIFESTATIONS
Pharyngoconjunctival fever:
– caused by adenoviruses types 3 and 7
– acute febrile illness
– low-grade fever is present for 3 - 5 days
– unilateral, than bilateral conjunctivitis
– a lot of granules of bulbar and palpebral conjunctivae
– rhinitis
– sore throat
– cervical lymphadenopathy
– duration of illness is 1 - 2 weeks
 ADENOVIRUS INFECTIONS
CLINICAL MANIFESTATIONS
Pharyngoconjunctival fever caused by
types 3 and 7
Acute diarrheal illness caused by types 40
and 4
Hemorrhagic cystitis caused by types 11
and 21
Epidemic keratoconjunctivitis caused by
types 8, 19, and 37
 PARAINFLUENZA VIRUS
INFECTIONS (ETIOLOGY)
Paramyxoviridae family
size 150 to 200 nm in diameter
contain a single-stranded RNA
genome
have four distinct serotypes and
several subtypes
Transmittion via respiratory
secrections (person-to-person contact
and/or by large droplets)
PARAINFLUENZA VIRUS INFECTIONS
(CLINICAL MANIFESTATIONS)
Incubation period 3 - 6 day
gradual onset of disease
stuffiness in nose, coryza
sore throat, tickle in a throat
systemic symptoms are mild
temperature is normal or subfebrile
dry, brassy or barking cough
hoarseness
nasopharyngeal discharge, oropharyngeal hyperaemia
duration usually 1 week
Complications in children:
– croup (brassy or barking cough progress to stridor, airway obstruction,
tachypnea, and hypoxia )
– bronchiolitis
– pneumonia
PARAINFLUENZA VIRUS INFECTIONS
TREATMENT
Only symptomatic treatment in adult
Mild cases of croup: bed rest and moist
aerosols
Severe cases of croup: hospitalization,
humidified oxygen, epinephrine and
aerosolized or systemically administered
glucocorticoids
 RESPIRATORY SYNCYTIAL VIRUS
INFECTIONS (RSV)
ETIOLOGY

Paramyxoviridae family
Pneumovirus genus
Size 150 to 300 nm in diameter
Contain a single-stranded RNA
genome
 RSV (EPIDEMIOLOGY)
Morbidity are highest among infants 1 to 6
months of age
RSV cause 75% of cases of bronchiolitis among
infants
RSV is transmitted:
– by close contact with contaminated fingers or fomites
– by self-inoculation of the conjunctiva or anterior
nostrils
– by aerosols produced by coughing or sneezing
RSV (CLINICAL MANIFESTATIONS)

RSV affect low respiratory tract (main clinical syndromes - severe

bronchiolitis or pneumonia)
Incubation period 4 - 6 days
In infants:
– rhinorrhea
– low-grade fever
– mild systemic symptoms
– cough and wheezing
– more severe illness: tachypnea, dyspnea, hypoxia, cyanosis,
and apnoea
Physical examination:
– diffuse wheezing, rhonchi, and rales
RSV (CLINICAL MANIFESTATIONS )
In adults:
– rhinorrhea
– sore throat
– cough
– systemic symptoms are moderate
Complications:
– pneumonia
– sinusitis
– otitis media
– worsening of chronic obstructive airway disease
 RSV(TREATMENT)
Treatment of upper respiratory tract RSV
is symptomatic
Treatment of lower respiratory tract RSV:
– respiratory therapy
– hydration
– suctioning of secretions
– humidified oxygen
– antibronchospastic agents
Antiviral treatment - aerosolized ribavirin
 ETIOLOGY

Family
Picornaviridae

Nonpolioviruses:
Coxsackie-
Polioviruses Genus viruses A,B
(type 1, 2, 3) Enteroviruses Echoviruses
Unclassified
Enteroviruses
 ETIOLOGY
Nonpolioviruses consist of:
1. Coxsackieviruses A – 23 types
2. Coxsackieviruses B – 6 types
3. Echoviruses – 28 types
4. Unclassified enteroviruses – types 67-
71
ECHO-viruses (Enteric Cytopathogenic
Hyman Orphans)
 ETIOLOGY

Structure of Enteroviruses:

Single-stranded RNA genome

Have four viral proteins
Have no lipid envelope
Small size 20-36 nm
 EPIDEMIOLOGY
Enteroviral infections:
are not race-specific
occur in all age groups
more common in young children and
infants
male-to-female ratio 2:1 (during the first
decade of the life) and 1:1 (during the next
decades of the life)
 TRANSMISSION
Fecal-oral route:
– via virus-contaminated food
– via virus-contaminated water
– via fecal-contaminated fingers or fomitis
Airborne transmission
Direct inoculation from the fingers to the
eye
Across the placenta from mother to fetus
 EPIDEMIOLOGY
Enteroviral infection has worldwide
distribution

In temperate climate Enteroviral infection

occurs in the summer and fall

In the tropics Enteroviral infection occurs

year-round
 PATHOGENESIS
1. Enteroviruses enter the human host
through the gastrointestinal or respiratory
tract
2. Viruses initially replicate in the epithelial
cells in the mucosa of the upper
respiratory tract and the distal small bowel
3. Viruses spread to and replicate in the
submucosal lymphoid tissue, tonsils and
Peyer’s patches, regional lymph nodes.
 PATHOGENESIS
4. Minor viremia
5. Dissemination in organs of the
reticuloendothelial system where the virus
replication continue
6. Secondary viremia
7. Immune response (specific Ig M, Ig G,
Ig A)
 CLINICAL CLASSIFICATION
1. Affection of CNS
- Aseptic Meningitis
- Meningoencephalitis
- Encephalitis
- Paralytic disease
- Guillain-Barre syndrome
2. Affection of skin and mucous membrane
- Hand-Foot-and-Mouth (HFM)
- Herpangina
- Viral exanthemas
- Acute Hemorrhagic Conjunctivitis (AHC)
 CLINICAL CLASSIFICATION
(Continue)
3. Affection of heart
- Myocarditis
- Pericarditis
4. Nonspecific febrile illnesses
5. Epidemic pleurodynia
6. Enteroviral Disease of the Newborn
NONSPECIFIC FEBRILE ILLNESS
(Summer Grippe)
incubation period 3 - 6 days
acute or sudden onset of disease
high temperature 38,5-400C
flulike syndrome (malaise, myalgia, headache)
sore throat
red face with pale nasolabial area
conjunctivitis
cervical lymphadenopathy
upper respiratory symptoms (cough, coryza)
gastrointestinal symptoms (nausea, diarrhea)
ENTEROVIRAL EXANTHEMAS

Occur in the summer and fall

2/3 of patients are children younger than 5 years
Responsible agents are echoviruses 9 and 16
Acute onset of disease
Fever
Intoxication (fatigue, malaise, headache)
Exanthemas:
– Rubelliform, morbilliform, roseole-like, makulopapular
(occur often)
– Vesicular, urticarial, petechial, purpuric (occur rare)
Hand-Foot-and-Mouth Disease
(HFM)
Responsibility agents are coxsackievirus
A16 or enterovirus 71
The disease is highly infectious (~100%)
Incubation period 4-6 days
Fever
Malaise, anorexia
Sore throat
Painless or less painful vesicles
Hand-Foot-and-Mouth Disease
(localization of rash)
on the buccal mucosa and tongue
on the dorsum of the hands (sometimes
on the palms)
1/3 patients – on the palate, uvula or
tonsillar pillars
1/3 patients – on the dorsum of feet and
soles
the truncal area is not involved
Hand-Foot-and-Mouth Disease
(Picture)
Hand-Foot-and-Mouth Disease
(Picture)
 HERPANGINA
Responsible agents – coxsackievirus A
Usually occurs in children 3-10 years old
Acute onset of diseases
Fever
Sore throat
Dyshpagia
Enanthema
 HERPANGINA
(Main features of enanthem)
Punctate macules – painful vesicles –
ulceration
3-5 vesicles
Diameter 1-2 mm
Localization: soft palate, anterior pillars of
the tonsils, tonsils, uvula, posterior
pharynx
Oropharynx is erythematous
Duration – 3-7 days
HERPANGINA
(Picture)
 ACUTE HEMORRHAGIC
CONJUNCTIVITIS (AHC)
This condition is highly contagious
Responsibility agents are enterovirus 70 and
coxsackievirus A24
Acute onset of diseases
Severe eye pain, photophobia, foreign body
sensation, watery discharge from the eye
Unilateral lesion:
- edema of the eyelids and chemosis
- subconjunctival hemorrhage, conjunctival follicles
- preauricular lymphadenopathy
Systemic symptoms are rarely (~20%)
 EPIDEMIC PLEURODYNIA
(devil’s grippe, Bornholm Disease)
Responsible agents are coxsackievirus B3 and
B5
Acute onset of diseases
Fever 39-400C
Severe muscular pains in the chest and upper
abdomen
Paroxysms of spasmodic pain last 15 to 30 min
Tenderness of involved muscles
Symptoms resolve in a few days
 EPIDEMIC PLEURODYNIA
You should differentiate epidemic
pleurodynia with:
– cardiac angina
– myocardial infarction
– acute abdomen
– pneumonia
– pulmonary infarct
– early zoster infection
MYOCARDITIS, PERICARDITIS

1/3 of cases of acute myocarditis caused by

Enteroviruses
2/3 cases occur in newborns, children, or young adults
2/3 of patients are male
Clinical manifestation: fever, chest pain, dyspnea,
malaise, pericardial friction rub, arrhythmias, and rarely
heart failure
Electrocardiogram shows: ST segment elevations or ST-
and T-wave abnormalities
Myocardial enzymes are elevated
 ASEPTIC MENINGITIS
Enteroviruses cause up to 90% of cases of
aseptic meningitis
Clinical manifestation:
– acute onset of fever, chills, malaise
– headache, neck pain, photophobia, and pain on eye
movement
– nausea, vomiting
– nuchal rigidity, Kernig and Brudzinski signs
Often combine with diarrhea, rash, epidemic
pleurodynia, myocarditis, and herpangina
 ASEPTIC MENINGITIS
(CSF)
CSF: polymorphonuclear pleocytosis
(polymorphonuclear leukocytes may
predominant) early in the course
shift to lymphocytic predominance within 24 h of
presentation
total count generally does not exceed 1000
cells/ml
normal glucose level
normal or slightly elevated level of protein
ENTEROVIRAL ENCEPHALITIS
5 to 10% of cases of viral encephalitis are
due to enteroviruses
Clinical manifestation:
– somnolence
– progressive lethargy
– disorientation
– sometimes convulsions
 PARALYTIC DISEASE
Responsible agents are enterovirus 70 or
71 and coxsackievirus A7 or A9
Occurs sporadically
Less severe than poliomyelitis
Main clinical manifestation: poliovirus-like
flaccid paresis or paralysis
Resolve within a 1-3 weeks
Recovery is completely
GENERALIZED DISEASE OF
THE NEWBORN
Sepsis-like condition:
– poor feeding
– fever
– Irritability
– lethargy
Complications:
– myocarditis and hypotension
– fulminant hepatitis with jaundice
– disseminated intravascular coagulation
– meningitis or meningoencephalitis
– pneumonia
 LABORATORY STUDIES
Viral culture
– Enterovirus may be isolated from the stool,
rectal swabs, nasopharyngeal, or throat
samples, CSF, serum, fluid from body cavities,
or tissues
Polymerase chain reaction (PCR)
Serologic diagnosis
– Serum should be collected 2 times
– Antibody serology titers must demonstrate a
4-fold rise
 TREATMENT
Normal diet
Symptomatic treatment:
– Fluid hydration
– Antipyretics (Acetaminophen ,Tylenol,
Feverall, Paracetamol, Panadol)
– NSAID – (Ibuprofen, Motrin, Ibuprin)
No specific antiviral treatment:
– Pleconaril (Picovir) is experimental drug
– Intravenous immunoglobulin (IVIG)