Viral Infections of the

Respiratory Tract

Fourth Medical,2007
.Prof. Widad Al-Nakib, FRCPath
Respiratory Infections are Common

• Most are fairly mild, self-limiting and

confined to the upper respiratory tract
(URT).

• Most are probably viral induced – at least

initially.

• However, in infants and children, URT

infections may spread downwards and
cause more severe infections and even
death.
Respiratory Tract Infections
 Upper Respiratory Tract (URT) Viral Infections

1. Colds. Watery to mucoid, sometimes purulent nasal discharge “coryza”.

Often preceded by a sore throat, sometimesaccompanied by fever and
often followed by transient opportunist bacterial infection.

2. Pharyngitis (“sore throat”). Generalised erythema of pharynx, not

localised to the tonsils and not associated with coryza. Some fever present.

3. Tonsilitis. Local infection of tonsils=red, swollen with exudate on the

surface.

4. Sinusitis & Otitis media. Painful inflammatory conditions of sinuses and

middle ear. Drainage of these spaces may be impaired and lead
to bacterial infection. (it is usually secondary to viral infection of the nose
and pharynx.)

5. Influenza. Fever, myalgia, sore throat, headache, prostration – usually NOT

much nasal discharge compared to a cold. Maybe some cough.
Lower Respiratory Tract (LRT) Viral Infections

1. Laryngo-Tracheo Bronchitis (Croup). An acute viral inflammation of

larynx and trachea in small children. Often preceded by a “cold”.
Accompanied by pyrexia, hoarseness, croaking cough, stridor,
restlessness. Can be fatal.

2. Acute Bronchitis. Inflammation of bronchi, accompanied by fever,

cough, wheezing and “noisy chest”.

3. Acute Bronchiolitis. Inflammation of terminal bronchioles in small

children. Complete plugging of bronchiole with air resorption leads
to collapse, and can be life-threatening. Usually preceded by coryzal
symptoms which later develops into the major pulmonary illness.
Clinically there is fever, rapid respiration, exhausting cough and
wheezing.

4. Pneumonia & Bronchopneumonia. Acute respiratory disease

accompanied by fever, restlessness and cyanosis. Often not much
clinical “consolidation”. Again, can be life-threatening.
Bronchitis and Emphysema
Viruses Associated with Respiratory Infections

Commonly Associated Less Commonly Associated Viruses

Syndrome Viruses
Colds Rhinoviruses, Coronaviruses Influenza and parainfluenza viruses,
enteroviruses, adenoviruses

Pharyngitis Parainluenza viruses Influenza viruses. CMV, EBV

Croup Parainfluenza viruses Influenza virus, RSV, hMPV,

adenoviruses
Bronchitis Parainfluenza viruses RSV, Influenza viruses

Bronchiolitis RSV, hMPV Influenza and parainfluenza viruses,

adenoviruses
Influenza Influenza viruses Parainfluenza viruses, adenoviruses

Bronchopneumonia Influenza virus, RSV, hMPV, Parainfluenza viruses, measles, VZV,

Adenoviruses CMV
SARS SARS-coronavirus -
 Influenza Virus

• RNA virus, genome

consists of 8 segments
• enveloped virus, with
haemagglutinin and
neuraminidase spikes
• 3 types: A, B, and C
• Type A undergoes
antigenic shift and drift.
• Type B undergoes
antigenic drift only and
type C is relatively stable
 Influenza Virus

• Undergoes “antigenic shifts” and “antigenic drifts” with

the haemagglutinin and neuraminidase proteins.

• Antigenic “shifts” of the haemagglutinin results in

pandemics. Antigenic “drifts” in the H and N proteins
result in epidemics.

• Usually causes a mild febrile illness.

• Death may result from complications such as

viral/bacterial pneumonia.
Epidemics and Pandemics
 .Contd

• Pandemics - influenza A pandemics arise when a

virus with a new haemagglutinin subtype emerges as
a result of antigenic shift. As a result, the population
has no immunity against the new strain. Antigenic
shifts had occurred 3 times in the 20th century.

• Epidemics - epidemics of influenza A and B arise

through more minor antigenic drifts as a result of
mutation.
 What Influenza Viruses Caused Past
? Pandemics

• 1889–1891 H3N8
• 1918–1919 H1N1
• 1957–1958 H2N2
• 1968–1969 H3N2
• This time H5NI
 ?’What Causes the ’Bird Flu

It is an influenza virus ,H5N1 sub-type •

 So Why Are We So Afraid of the
?“’Bird Flu

• Because the ‘Bird Flu’ is a new strain of influenza virus to

humans and humans have no antibody against it to
protect them?
• So if the ‘Bird Flu’ virus adapts to grow in humans and
it can spread from human to human it will cause
infections world-wide, the so called “pandemic”, with
very serious consequence and probably high
mortality rate everywhere.
• That is why the WHO is very worried and wants
everybody to be prepared. In the 1918-1919 pandemic
40 million people died
 So why is the ’Bird Flu” a serious
?disease in humans

• The virus infects the lower

respiratory tract causing
pneumonia and multiple organ
failure leading usually to death in
these patients. Recent cases
reported in the N. Eng. Med. shows
that patients can present atypically
with diarrhea, fever, encephalitis
and usually die. Virus was found in
faeces, blood and CSF
How Do Humans Get Infected with Avian
?Influenza Virus
 Treatment
• Amantidine is effective against influenza A if
given early in the illness. However, resistance to
amantidine emerges rapidly
• Rimantidine is similar to amantidine but but
fewer neurological side effects.
• Ribavirin is thought to be effective against both
influenza A and B.
• Neuraminidase inhibitors (Oseltamivir,
Zanamivir) .They are highly effective and have
fewer side effects than amantidine. Moreover,
resistance to these agents emerge slowly
 Prevention

• Inactivated whole/split/subunit vaccines are available

against influenza A and B.
• The vaccine is normally trivalent, consisting of one A
H3N2 strain, one A H1N1 strain, and one B strain.
• The strains used are reviewed by the WHO each year.
• The vaccine should be given to debilitated and elderly
individuals who are at risk of severe influenza
infection.
• Oseltamivir or Zanamivir can be used for those who
are allergic to the vaccine or during the period before
the vaccine takes effect.
 Parainfluenza viruses

• Enveloped, pleomorphic
morphology
• 5 serotypes: 1, 2, 3, 4a and
4b
• ssRNA virus
• No common group
antigen, HN, F proteins

• Closely related to Mumps

virus
 Clinical Manifestations

• Croup (laryngo-tracheo-bronchitis) - most

common manifestation of parainfluenza virus
infection. However other viruses may induce
croup e.g. influenza, RSV and hMPV.
Other conditions that may be caused by
parainfluenza viruses include bronchiolitis,
pneumonia, flu-like tracheo-bronchitis, and
coryza-like illnesses.
 (Respiratory Syncitial Virus (RSV

• Most common cause of severe lower

respiratory tract disease in infants,
responsible for 50-90% of bronchiolitis and
5-40% of bronchopneumonia
• Other manifestations include croup (10% of
all cases).
• In older children and adults, the symptoms
are much milder: it may cause a coryza-like
illness or bronchitis.
 ?Infants at Most Risk

1. Infants with congenital heart disease - infants who

were hospitalized within the first few days of life
with congenital disease are particularly at risk.
2. Infants with underlying pulmonary disease - infants
with underlying pulmonary disease, especially
bronchopulmonary dysplasia, are at risk of
developing prolonged infection with RSV.
3. Immunocompromized infants - children who are
immunosuppressed or have a congenital
immunodeficiency disease may develop lower
respiratory tract disease at any age.
(Human Metapneumovirus (hMPV

Clinical symptoms
associated with the new
virus are similar to those
caused by human
respiratory syncytial virus
(RSV) infection, ranging
from upper respiratory
tract disease to severe
bronchiolitis and
pneumonia. By the age of
5 years most children are
infected.
 Adenoviruses

Pharyngitis (1, 2, 3, 5, 7)
Pharyngoconjunctival fever (3, 7)
Acute respiratory disease of recruits
(4, 7, 14, 21)
Pneumonia (1, 2, 3, 7)
Pertussis-like syndrome (5)
Follicular conjunctivitis (3, 4, 11)
Epidemic keratoconjunctivitis
(8, 19, 37)
Acute haemorrhaghic cystitis (11, 21)
Acute infantile gastroenteritis (40, 41)
Intussusception (1, 2, 5)
Severe disease in AIDS and other
immunocompromized patients
(5, 34, 35, >41)
Meningitis
 Management

• There is no specific antiviral therapy.

• A vaccine is available against Adult Respiratory

Distress Syndrome (ARDS). It consists “live”
adenovirus 4, 7, and 21 in “enterically” coated
capsules. It is given to new recruits into various
arm forces around the world.
 Common Cold Viruses

• Common colds account for one-third to one-half of all

acute respiratory infections in humans.
• Rhinoviruses are responsible for 30-50% of common
colds, Coronaviruses for 10-30% of all respiratory
infections.
• The rest are due to adenoviruses, enteroviruses, RSV,
influenza, and parainfluenza viruses, which may cause
symptoms indistinguishable to those of rhinoviruses
and coronaviruses.
 Laboratory Diagnosis of Respiratory Virus
Infections
• Detection of Antigen - a rapid diagnosis can be made by the detection
of viral antigen in nasopharyngeal aspirates, throat washings and
other respiratory samples by IF and ELISA.

• RT-PCR- detecting the viral genome in respiratory secretions and

other samples.

• Virus Isolation - virus may be readily isolated from nasopharyngeal

aspirates and throat swabs.

• Serology - a retrospective diagnosis may be made by detecting

significant virus antibody (greater than 4-fold) between blood samples
collected at the acute phase and one at the convalescent phase using
serological assays such as CFT, HAI or EIA.
A ’Novel’ Coronavirus Associated with SARS
 SARS-Corona virus

• SARS-Coronavirus has recently been

associated to be the cause of severe
acute respiratory syndrome (SARS)
with a relatively high mortality rate. The
‘new’ virus is thought to have jumped ‘
species’ and became able to infect man
with serious consequences.
 Methods Used to Identify the Causative
Agent of SARS

• Virus isolation in Vero cell lines

• Viral antigen detection (directly in
specimen and/or in culture)
• Electron Microscopy
• Amplifying the viral genome indirectly in
specimen and/or in culture using RT-PCR
 SARS-Corona Virus

SARS remains an ongoing problem

internationally, and the virus is to some extent is
partially contained but may well spread
internationally. If it does, the consequences will
be quite devastating as currently, we do not
have any treatment nor a vaccine to prevent it.
However it remains a “hot” topic for research
especially with regards to the development of a
vaccine and antiviral chemotherapy.