Download Respiratory syndrom

TASHKENT MEDICAL ACADEMY
Infectious and children
infectious diseases department
Theme: Early and Comparative
diagnosis of diseases with the
respiratory syndrome
Lecturer:
Viruses Associated with
Respiratory Infections
Syndrome
Commonly Associated Viruses
Less Commonly Associated Viruses
Corza
Rhinoviruses, Coronaviruses
Influenza and parainfluenza viruses,
enteroviruses, adenoviruses
Influenza
Influenza viruses
Parainfluenza viruses, adenoviruses
Croup
Parainfluenza viruses
Influenza virus, RSV, adenoviruses
Bronchiolitis
RSV
Influenza and parainfluenza viruses,
adenoviruses
Bronchopneumonia
Influenza virus, RSV, Adenoviruses Parainfluenza viruses, measles, VZV, CMV
Influenza Virus
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(Courtesy of Linda Stannard,
University of Cape Town, S.A.)
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 A 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.
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Usually causes a mild febrile illness.
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Death may result from complications such as
viral/bacterial pneumonia.
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Epidemiology

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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.
Past Antigenic Shifts
1918 H1N1 “Spanish Influenza”
20-40 million deaths
1957
H2N2 “Asian Flu”
1-2 million deaths
1968
H3N2 “Hong Kong Flu”
700,000 deaths
1977 H1N1 Re-emergence
2009 H1N1 “Swine Flu
No pandemic
Mild Pandemic
At least 15 HA subtypes and 9 NA subtypes occur in nature.
Up until 1997, only viruses of H1, H2, and H3 are known to
infect and cause disease in humans.
Avian Influenza
H5N1
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An outbreak of Avian Influenza H5N1 occurred in Hong Kong in 1997 where 18
persons were infected of which 6 died.
The source of the virus was probably from infected chickens and the outbreak
was eventually controlled by a mass slaughter of chickens in the territory.
All strains of the infecting virus were totally avian in origin and there was no
evidence of reassortment.
However, the strains involved were highly virulent for their natural avian hosts.
H9N2
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Several cases of human infection with avian H9N2 virus occurred in Hong Kong
and Southern China in 1999.
The disease was mild and all patients made a complete recovery
Again, there was no evidence of reassortment
Theories Behind Antigenic Shift
1. Reassortment - Reassortment of the H and N genes between
human and avian influenza viruses through a third host. There
is good evidence that this occurred in the 1957 H2N2 and the
1968 H3N2 pandemics. The 2009 pandemic virus was
thought to be novel virus that was a triple re-assortant
involving human, bird, N. American pig and Eurasian pig
viruses.
2. Recycling of pre-existing strains – this probably occurred in
1977 when H1N1 re-surfaced.
3. Gradual adaptation of avian influenza viruses to human
transmission. There is some evidence that this occurred in the
1918 H1N1 pandemic.
Reassortment
Avian H3
Human H2
Human H3
Laboratory Diagnosis
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Rapid Diagnosis – nasopharyngeal aspirates, throat and
nasal swabs are normally used.
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Antigen Detection – can be done by IFT or EIA
RNA Detction – RT-PCR assays give the best sensitivity and
specificity. It is the only method that can differentiate the 2009
pandemic H1N1 strain from the seasonal H1N1 strain. However, it
is expensive and technically demanding.
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Virus Isolation - virus may be readily isolated from
nasopharyngeal aspirates and throat swabs.
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Serology - a retrospective diagnosis may be made by
serology. CFT most widely used. HAI and EIA may be
used to give a type-specific diagnosis
Management
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Neuraminidase inhibitors - are now the drugs. They are highly
effective and have fewer side effects than amantidine. Oseltamivir
(Tamiflu) is the most commonly used agent as it can be given
orally unlike Zanamivir (Relenza). The resistance to different
types varies enormously year to year. H3N2 strains were mainly
sensitive whereas seasonal H1N1 were almost totally resistant.
More than 98% of the 2009 pandemic influenza H1N1 tested were
sensitive.
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.
Prevention
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Inactivated 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.
Amantidine can be used as an prophylaxis for those who
are allergic to the vaccine or during the period before the
vaccine takes effect.
Parainfluenza Virus
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(Linda Stannard, University of Cape Town, S.A.)
ssRNA virus
enveloped, pleomorphic
morphology
5 serotypes: 1, 2, 3, 4a and
4b
No common group antigen
Closely related to Mumps
virus
Clinical Manifestations
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Croup (laryngotraheobroncitis) - most common
manifestation of parainfluenza virus infection. However
other viruses may induce croup e.g. influenza and RSV.
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Other conditions that may be caused by parainfluenza
viruses include Bronchiolitis, Pneumonia, Flu-like
tracheobronchitis, and Corza-like illnesses.
Laboratory Diagnosis

Detection of Antigen - a rapid diagnosis can be made by
the
detection
of
parainfluenza
antigen
from
nasopharyngeal aspirates and throat washings.

Virus Isolation - virus may be readily isolated from
nasopharyngeal aspirates and throat swabs.
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Serology - a retrospective diagnosis may be made by
serology. CFT most widely used.
Management
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No specific antiviral chemotherapy available.
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Severe cases of croup should be admitted to
hospital and placed in oxygen tents.
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No vaccine is available.
Respiratory Syncytial Virus (RSV)
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ssRNA eveloped virus.
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belong to the genus Pneumovirus of the Paramyxovirus
family.
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Considerable strain variation exists, may be classified into
subgroups A and B by monoclonal sera.
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Both subgroups circulate in the community at any one
time.
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Causes a sizable epidemic each year.
Clinical Manifestations
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Most common cause of severe lower respiratory
tract disease in infants, responsible for 50-90% of
Bronchiolitis and 5-40% of Bronchopneumonia
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Other manifestations include croup (10% of all
cases).
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In older children and adults, the symptoms are
much milder: it may cause a corza-like illness or
bronchitis.
Infants at Risk of Severe
Infection
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.
Laboratory Diagnosis
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Detection of Antigen - a rapid diagnosis can be made by
the detection of RSV antigen from nasopharyngeal
aspirates. A rapid diagnosis is important because of the
availability of therapy
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Virus Isolation - virus may be readily isolated from
nasopharyngeal aspirates. However, this will take several
days.
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Serology - a retrospective diagnosis may be made by
serology. CFT most widely used.
Treatment and Prevention
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Aerosolised ribavirin can be used for infants with severe
infection, and for those at risk of severe disease.
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There is no vaccine available.
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RSV immunoglobulin can be used to protect infants at risk
of severe RSV disease.
Adenovirus
(Linda Stannard, University of Cape Town, S.A.)
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ds DNA virus
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non-enveloped
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At least 47 serotypes are
known
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classified into 6 subgenera:
A to F
Clinical Syndromes
1. Pharyngitis 1, 2, 3, 5, 7
2. Pharyngoconjunctival fever 3, 7
3. Acute respiratory disease of recruits 4, 7, 14, 21
4. Pneumonia 1, 2, 3, 7
5. Follicular conjunctivitis 3, 4, 11
6. Epidemic keratoconjunctivitis 8, 19, 37
7. Pertussis-like syndrome 5
8. Acute haemorrhaghic cystitis 11, 21
9. Acute infantile gastroenteritis 40, 41
10.Intussusception 1, 2, 5
11.Severe disease in AIDS and other immunocompromized patients 5,
34, 35
12. Meningitis 3, 7
Laboratory Diagnosis
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Detection of Antigen - a rapid diagnosis can be made by
the detection of adenovirus antigen from nasopharyngeal
aspirates and throat washings.
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Virus Isolation - virus may be readily isolated from
nasopharyngeal aspirates, throat swabs, and faeces.
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Serology - a retrospective diagnosis may be made by
serology. CFT most widely used.
Treatment and Prevention
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There is no specific antiviral therapy.
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A vaccine is available against Adult Respiratory
Distress Syndrome. 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
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Common colds account for one-third to one-half of all
acute respiratory infections in humans.
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Rhinoviruses are responsible for 30-50% of common
colds, coronaviruses 10-30%.
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The rest are due to adenoviruses, enteroviruses, RSV,
influenza, and parainfluenza viruses, which may cause
symptoms indistinguishable to those of rhinoviruses and
coronaviruses.
Rhinovirus
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Reconstructed Image of rhinovirus particle (Institute
for Molecular Virology)
ssRNA virus
Belong to the picornavirus
family
ssRNA virus
acid-labile
at least 100 serotypes are
known
Coronavirus
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ssRNA Virus
Enveloped, pleomorphic
morphology
2 serogroups: OC43 and
229E
Measles
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Highly contagious viral illness
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First described in 7th century
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Near universal infection of childhood
in prevaccination era
Frequent and often fatal in developing
areas
Measles Virus
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Paramyxovirus (RNA)
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One antigenic type
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Hemagglutinin important surface
antigen
Rapidly inactivated by heat and light
Measles Pathogenesis
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Respiratory transmission of virus
Replication in nasopharynx and regional
lymph nodes
Primary viremia 2-3 days after exposure
Secondary viremia 5-7 days after
exposure with spread to tissues
Measles Clinical Features
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Incubation period 10-12 days
Prodrome
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Stepwise increase in fever to 103 F
or higher
Cough, coryza, conjunctivitis
Koplik spots
Measles Clinical Features
Rash
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2-4 days after prodrome, 14 days after
exposure
Maculopapular, becomes confluent
Begins on face and head
Persists 5-6 days
Fades in order of appearance
Measles Complications
Condition
Diarrhea
Otitis media
Pneumonia
Encephalitis
Death
Hospitalization
Percent reported
8
7
6
0.1
0.2
18
Based on 1985-1992 surveillance
data
Measles Complications by Age Group
30
Pneumonia
Hospitalization
25
Percent
20
15
10
5
0
<5
5-19
Age group (yrs)
20+
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Measles
Laboratory
Isolation
of measles
virus fromDiagnosis
a clinical
specimen (e.g., nasopharynx, urine)
Significant rise in measles IgG by any
standard serologic assay (e.g., EIA, HA)
Positive serologic test for measles IgM
antibody
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Measles
Epidemiology
Reservoir
Human
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Transmission
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Temporal pattern
Peak in late winter and spring
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Communicability
4 days before to 4 days after
rash onset
Respiratory
Airborne
Measles – United States, 1950-2001*
Cases (thousands)
900
800
Vaccine Licensed
700
600
500
400
300
200
100
0
1950
1960
*2001 provisional data
1970
1980
1990
2000
Measles – United States, 1980-2001*
30000
25000
Cases
20000
15000
10000
5000
0
80
82
84
86
*2001 provisional data
88
90
92
94
96
98
'00
Age Distribution of Reported
Measles, 1975-2000
90
Preschool-age
School-age
Adult
80
Percent
70
60
50
40
30
20
10
0
1975
1980
1985
1990
Age group (yrs)
1995
2000
Measles Resurgence – United
States, 1989-1991
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Cases
55,622
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Age group affected
Children <5
yrs
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Hospitalizations
>11,000
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Deaths
123
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Direct medical costs >$150 million
Measles 1993-2001
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Endemic transmission interrupted
Record low annual total in 2000
(86 total cases)
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Many cases among adults
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Many cases due to importation
Measles Clinical Case Definition
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Generalized rash lasting >3 days, and
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Temperature >38.3 C (101 F), and
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Cough, coryza, or conjunctivitis
Measles Vaccines
1963
1965
1967
1968
1971
1989
Live attenuated and killed vaccines
Live further attenuated vaccine
Killed vaccine withdrawn
Live further attenuated vaccine
(Edmonston-Enders strain)
Licensure of combined measlesmumps-rubella vaccine
Two dose schedule
Measles Vaccine
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Composition
Live virus
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Efficacy
95% (range, 90%-98%)
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Duration of
Immunity
Schedule
Lifelong
2 doses
Should be administered with mumps and
rubella as MMR
MMR Vaccine Failure
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Measles, mumps, or rubella disease (or lack of
immunity) in a previously vaccinated person
2%-5% of recipients do not respond to the
first dose
Caused by antibody, damaged vaccine, record
errors
Most persons with vaccine failure will respond
to second dose
Measles (MMR) Vaccine
Indications
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All infants >12 months of age
Susceptible adolescents and adults
without documented evidence of
immunity
Measles Mumps Rubella Vaccine
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12 months is the recommended and
minimum age
MMR given before 12 months should
not be counted as a valid dose
Revaccinate at >12 months of age
Second Dose of Measles Vaccine
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Intended to produce measles immunity
in persons who failed to respond to the
first dose (primary vaccine failure)
May boost antibody titers in some
persons
Second Dose Recommendation
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First dose of MMR at 12-15 months
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Second dose of MMR at 4-6 years
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Second dose may be given any time >4
weeks after the first dose
ACIP Recommendations
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All states ensure that 2 doses of MMR
required for school entry
All children in kindergarten through
grade 12 have 2 doses of MMR by 2001
Adults at Increased Risk
of Measles
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College students
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International travelers
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Health-care personnel
Measles Immunity in
Health Care Personnel
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All persons who work in
medical facilities should be
immune to measles
Measles Immunity
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Born before 1957
Documentation of physiciandiagnosed measles
Serologic evidence of immunity
Documentation of receipt of
measles-containing vaccine
Measles Vaccine
Indications for Revaccination
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Vaccinated before the first birthday
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Vaccinated with killed measles vaccine
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Vaccinated prior to 1968 with an
unknown type of vaccine
Vaccinated with IG in addition to a
further attenuated strain or vaccine of
unknown type
MMR Adverse Reactions
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Fever
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Rash
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Joint symptoms
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Thrombocytopenia
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Parotitis
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Deafness
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Encephalopathy
5%-15%
5%
25%
<1/30,000 doses
rare
rare
<1/1,000,000 doses
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MMR Vaccine and Autism
Measles vaccine connection first
suggested by British
gastroenterologist
Diagnosis of autism often made in
second year of life
Multiple studies have shown no
association
MMR Vaccine and Autism
“The evidence favors a rejection of a
causal relationship at the population
level between MMR vaccine and
autism spectrum disorders (ASD).”
- Institute of Medicine, April 2001
MMR Vaccine
Contraindications and Precautions

Severe allergic reaction to prior dose or
vaccine component
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Pregnancy
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Immunosuppression
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Moderate or severe acute illness
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Recent blood product
Measles and Mumps Vaccines
and Egg Allergy
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Measles and mumps viruses grown in
chick embryo fibroblast culture
Studies have demonstrated safety of
MMR in egg allergic children
Vaccinate without testing
Measles Vaccine and HIV Infection
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MMR recommended for persons with
asymptomatic and mildly symptomatic
HIV infection
NOT recommended for those with
evidence of severe immuno- suppression
Prevaccination HIV testing not
recommended
PPD and Measles Vaccine

Apply PPD at same visit as MMR

Delay PPD >4 weeks if MMR given first
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Apply PPD first - give MMR when skin
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