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CHAPTER 178 – COMMON VIRAL RESPIRATORY INFECTIONS AND  Psychologically defined “stress” – may contribute to

SEVERE ACUTE RESPIRATORY SYNDROME (SARS) p.1059-1065 development of symptoms


 Neutralizing antibodies to multiple serotypes by
General Conditions adulthood, although the presence of antibody to one
 Acute viral respiratory illnesses- among most common serotype varies
cause of human diseases, about ½ or more of acute
illnesses
 Multiple serotypes circulate simultaneously and no
single serotype or group of serotypes has been more
 Incidence in US – 3-5.6 cases/ person/yr prevalent than the others
 Highest among children <1 yr old, remains high til Pathogenesis
6y.o., then a progressive decline begin
 Adults: 3-4 cases/person/yr  Infect cells through attachment to specific cellular
receptors (ICAM-1 , LDL-r)
 Morbidity: 30-50% time lost from work by adults; 60-
80% lost from school by children  Nasal mucosa is edematous, hyperemic, during acute
 Use of anti-bacterial agents for viral respiratory illness, covered by mucous discharge
infections – major source of drug abuse  Mild infiltrate with inflammatory cells (neutrophils,
 2/3 – ¾ of acute respiratory illness – caused by viruses lymphocytes, plasma cells, eosinophils)
 URT- involved but LRT involved in lower age groups  Hyperactive mucus-secreting glands in the submucosa,
engorged nasal turbinates leading to obstruction of
 Divided into multiple distinct syndromes – “common
openings of sinus cavities
cold”, pharyngitis, croup (laryngotrachebronchitis),
tracheitis, bronchiolitis, bronchitis, and pneumonia  Mediators linked to S/Sx – bradykinin, lysylbradykinins,
histamine, prostaglandin, IL- 1, 6, 8
 Croup – occurs in very young children and a
characteristic clinical course  Short incubation period (1 – 2 days)
 can be associated with other virus like common cold  Viruses coincides with theonset of illness or shortly
with rhinovirus before symptoms develop
 occupies epidemiologic niches like adenovirus  Mechanism of immunity ot well worked out
infections in military recruits  Homotypic antibody associated with reduced rates of
 Refer Table 170-1 subsequent infection and illness
Clinical Manifestation
 Most respiratory viruses could cause more than one
type of respiratory illness, and frequently features  Common cold- most common manifestation
several types of illness found in the same patient  Begins with rhinorrhea and sneezing accompanied by
 Clinical illnesses induced by the viruse are rarely nasal congestion
sufficiently distinctive to permit an etiologic diagnosis  Sore throat – in some cases initial complaint
on clinical grounds alone, although the epidemiologic  Malaise and headache are mild or absent, fever is
setting increases the likelihood that one group rather unusual
than the other is involved  Illness lasts 4-9 days and resolves spontaneously
without sequelae
RHINOVIRUS INFECTION  In children, bronchitis, bronchiolitis, and
bronchopneumonia reported
Etiologic Agent  But not major causes of LRT in children
 Member of Picornaviridae family, small non-enveloped,  May cause exacerbations of asthma and chronic
ssRNA, acid-labile, completely inactivated at pH < 3 pulmonary disease in adults
 Grow preferentially at 33 – 34 C – tem of human nasal  Complications such as otits media, acute sinusitis
passages rather than at higher temp (37 C) of LRT  In bonemarrow transplant patients, fatal pneumonias
 102 distinct serotypes are recognized; 91 – use ICAM-1 may develop
as a cellular receptor and comprise the “major” Diagnosis
receptor; 10 – use the LDL receptor comprises the  Etiologic diagnosis cannot be made on clinical grounds
“minor” receptor group; 1 uses a sialoprotein cellular alone
receptor
 Diagnosed by isolation of the virus from nasal washes
Epidemiology
or secretions in tissue culture but this is rarely
 Major cause of common cold and isolated from 15-40% undertaken due to the benign course of illness
of adults with common-cold like illnesses
 PCR is more sensitive but done in research procedure
 Over-all rates of infection are higher among infants
 Diagnosis by serum antibody impractical due to many
and young children and decreases with increasing age
serotypes present
 Occur throughout the year, with seasonal peaks in early
 WBC count and ESR not helpful
fall and spring in temperate climates.
Treatment
 Introduced into families by pre-school or grade-school
 Treatment is not necessary
children <6 years old
 25-70% - of initial illnesses in family settings are  In patients with pronounced Sx, 1st generation anti-
followed by secondary causes. With highest attack histamines and NSAIDS beneficial; oral decongestant if
rates among youngest siblings at home nasal obstruction is present
 Attack rates also increase with family size  Anti-bacterial agents if with bacterial complications
 Spreads through direct contact with infected such as otitis media, sinusitis
secretions usually respiratory droplets Prevention
 Interferon sprays effective but local nasal irritation
 Hand-to-hand contact with subsequent self-inoculation occurs
of the conjunctival or nasal mucosa.
 Experminetal vaccines with questionable results
 Transmission by large or small particle aerosol was
 Antibodies to ICAM-1 not effective
demonstrated
 Handwashing, environmental decontamination,
 Viruses can be recovered from plastic surfaces
protection against autoinoculation help reduce rates of
inoculated 1 – 3h previously suggesting environmental
transmission
surfaces contribute to transmission
 In married couples in which neither partner had CORONA VIRUS INCLUDING SARS
detectable serum antibody, transmission was
associated with prolonged contact (>122h) during a 7- Etiologic Agent
day period  Pleomorphic, ssRNA, measures 100-150nm in dm
 Transmission is infrequent unless virus is recovered fro  Crown-like produced by the club-shaped projections
the donor’s hands and and nasal mucosa at least 1000 that stud the viral envelope
TCID50 of virus was present in nasal washes from the  Group I (HCoV-229E) and Group II (HCoV-OC43) infects
donor, and the donor was at least moderately humans
symptomatic with “cold”  SARS (SARS-CoV) – shows minimal variation
 Exposure to cold temeperature, fatigue, sleep  Difficult to cultivate in vitro, grows only human
deprivation not associated with increased rates of tracheal organ cultures rather than in tissue culture
illness
 Except SARS-CoV- grows in African green monkey  Elevated aminotransferases, creatinine kinases, lactate
kidney (Vero E6) dehydrogenases
Epidemiology  SARS-CoV can be grown from respiratory tract samples
 Coronavirus infection spread throughout the world by inoculation into Vero E6 tissue culture cells –
 Strains of HCoV-229E and HCoV-OC43 demonstrated cytopathic effect can be seen
that serum antibodies acquired early in life and  Rapid diagnosis: RT-PCR of respi tract samples and
increase in prevalence with advancing age, so that plasma, early in illness, and urine and stool later on
>80% of adult populations have antibodies measured  RT-PCR more sensitive than tissue culture but only 1/3
by ELISA are positive by PCR at initial presentation
 10-35% of common colds caused by coronavirus  Serum antibodies can be detected by ELISA or
 Prevalent in late fall, winter, early spring – times when immunofluorescence, develops detectable serum
rhinovirus infection are less common antibodies within 28d after onset of illness
 SARS began in Guangdong Province of China in  Lab dx of corona-virus induced colds is rarely required,
November 2002 originated from contact with but can be detected by ELISA or IF assays or by RT-PCR
semidomesticated animals such as the palm civet or Treatment
the dog raccoon, animals prized as edible delicacies  No specific therapy for SARS, though ribavirin is used
that harbor CoV ut no beneficial effect on the illness
 Nov16, ’02 – Feb28,’03 : 792 cases of SARS in Guandong  Glucocorticoids given due to immunopathologic
 Healthcare workers and their contacts account for evidence
most cases  Supportive care to maintain pulmonary and other organ
 Index case that introduce SARS into HK – physician system functions – mainstay of therapy
from Guandong that travelledto HK  Corona virus induced common colds’ therapy similar
 Similar cases were noted in Singapore, Thailand, with rhinovirus’
Vietnam, Taiwan, and Toronto Prevention
 8422 cases identified in 28 countries; 90% occurred in  Infection control practices, travel advisories,
China and Hongkong quarantines
 Over-asll figure of case-datality rate – 11%  Absence of new cases for 30 days (3x the estimated
 Milder cases in US and in children incubation pd of 10d for the disease), travel advisories
were lifted
 Mechanism of transmission incompletely understood  Strict infection control practices in health care
 Spread may occur by both large and small aerosols and facilities
perhaps by fecal-oral route, environmental sources  Vaccines against animal CoV, but none yet for human
such as sewage and water CoV
 Individuals may be hyperinfectious or super spreaders
capable of transmitting infection to 10-40 contacts, Respiratory Syncytial Virus Infection
although most infections resulted in spread either to 1-
3 individuals Etiologic Agent:
Pathogenesis
 Infect the ciliated epithelial cells in the nasopharynx - RSV member of Paramyxoviridae family.
Genus Pneumovirus.
 Viral replication leads to damage of ciliated cells and - A single-stranded RNA, enveloped virus
induction of chemkines and IL, resulting in common ,150-300 nm diameter codes for 11 virus-
cold symptoms specific proteins.
 Systemic illness in which virus likely enters the - Replication in vitro leads to fusion of
bloodstream, in the urine, and (for up to 2 months) in neighboring cells into large
the stool. multinucleated syncytia.
 Virus persists in the respiratory tract for 2-3 wks, and
titers peak ~10 days after the onset of systemic illness
- Viral RNA contained in a helical
nucleocapsid surrounded by a lipid
 Pulmonary pathology consists of hyaline membrane
envelope bearing 2 glycoproteins: G
formation, desquamation of pneumocytes in alveolar
protein, virus attaches to the cells, F
spaces, and an interstitial infiltrate consisting of
(fusion)protein, facilitates entry of virus
lymphocytes and mononuclear cells, giant cells are
into the cell by fusing host and viral
frequently seen, coronavirus detected in TypeII
membranes.
pneumocytes
Clinical Manifestations - Antigenic diversity is reflected by
 2-7 d incubation pd (range is 1-10d) difference in G protein while F protein is
highly conserved.
 Begins as a systemic illness marked by onset of fever
accompanied by malaise, headache, myalgia, and Epidemiology:
followed in 1-2 days by a non-productive cough and
dyspnea; 25% have diarrhea - major respiratory pathogen of young
 CXR showed infiltrates such as patchy areas of children
consolidation, most frequently in peripheral and lower - foremost cause of LRTI in infants
kung field; or interstitial infiltrates progressing to - occur in winter or spring, late fall and
diffuse involvement lasts up to 5 mos.
 In severe cases, respiratory function may worsen - Highest among infants 1-6 mos of age.
during tha 2nd week and progress to ARDS with PEAK: 2-3mos.
multiorgan dysfunction - Age 2 - all children will be infected
 Risk fxs for severity: age >50; comorbidities such as - Common cold-like syndrome illness – most
CVD, diabetes, hepatitis; pregnancy commonly associated with adults.
 Clinical features similar with rhinoviruses - Severe LRTI w/ pneumonitis – occur in
 In a study, mean incubation period – 3d, longer than elderly, immunocompromised disorders or
rhinoviruses; duration is shorter, mean of 6-7; amount tx ( recipients of bone-marrow and
of nasal discharge is greater in colds induced by solid0organ transplants)
coronaviruses - important nosocomial pathogen
 Coronaviruses recovered from infants with pneumonia - TRANSMISSION: close contact w/
and from military recruits with LRT disease and contaminated fingers or fomites
associated with worsening chronic bronchitis Self-inoculation of the
conjunctivae or anterior nares
Laboratory Findings and Diagnosis Coarse aerosols produced by
 Lymphopenia in ~50% of cases mostly affecting CD4+ coughing and sneezing
Tcells but also CD8+ Tcells and NK cells - INCUBATION period: 4-6 days,
 Total WBC- normal or slightly low; thrombocytopenia virus shedding last for > 2 weeks
as disease develops in children and for shorter
periods for adults and multiple nephrotic syndrome or
weeks for immunocompromised immunosuppression)
patient. - Combined therapy w/ aerosolized
ribavirin and palivizumab is being
Pathogenesis: evaluated in the treatment of
immunosuppressed patients w/ RSV
- Severe bronchiolitis or pneumonia – pneumonia.
necrosis of the bronchiolar epithelium
and a peribronchiolar infiltrate of Prevention:
lymphocytes and mononuclear cells.
- interalveolar thickening and filling of - RSVIg or palivizumab approved as
alveolar spaces w/ fluid can be also prophylaxis against RSV for children < 2
found. yrs of age who have bronchopulmonary
- Studies indicate that the presence of dysplasia or were born prematurely.
nasal IgA neutralizing antibody correlates
more closely w/ protection than the Metapneumovirus Infections
presence of serum antibody.
- viral respiratory pathogen of
Clinical Manifestations: Paramyxoviridae family Genus
Metapneumovirus
- Infants - LRT involvement includes - morphology and genomic organization
pneumonia, bronchiolitis and similar to respi pathogen of turkeys
tracheobronchitis. - spherical, filamentous or pleomorphic in
- begins most frequently w/ shape and measure 60-280 nm in
rhinorrhea, low-grade fever and mild diameter.
systemic symptoms often - Initially detected in nasal aspirates
accompanied by cough and wheezing. - Most frequent during winter and occur
- Recover gradually over 1-2 early in life. Serum antibodies to the
weeks. virus are present in nearly all children by
- SEVERE illness in premature, born age 5.
w/CHD, bronchopulmonary dysplasia, - Detected thru nasal aspirates and respi
nephrotic syndrome or secretions by PCR or by growth in rhesus
immunosuppression. Tachypnea and monkey kidney tissue cultures.
dyspnea develop and eventually - Serologic diagnosis made by ELISA w/c
frank hypoxia, cyanosis and apnea utilizes HMPV-infected tissue culture
ensue. lysates as sources of antigens.
- PE: diffuse wheezing, rhonchi
and rales. Parainfluenza Virus Infections
- Chest radiography: hyperexpansion,
peribronchial thickening and variable Etiologic Agent:
infiltrates ranging from diffuse
interstitial infiltrates to segmental or - belong to Paramyxoviridae family Genus
lobar consolidation. Respirovirus and Rubulavirus
- Adults – common cold, w/ rhinorrhea, - 150-200 nm in diameter, enveloped and
sorethroat, and cough. single stranded RNA enclosed in helical
- associated w/ moderate nucleocapsid and codes for six structural
systemic symptoms such as and several accessory proteins.
malaise, headache and fever. - studded w/ 2 glycoproteins: both
- cause of morbidity and mortality in hemagglutinin and neuraminidase activity
patients undergoing bone marrow and and other fusion activity
solid-organ transplantation
- sinusitis, otitis media and worsening of Epidemiology:
chronic obstructive and reactive airway
disease associated w/RSV infection. - type 4 difficult to grow in tissue cultures
- infxn acquired early childhood, by age 5
Lab findings and Diagnosis: most children have antibodies to
serotypes 1,2 and 3.
- isolated in tissue culture and identified - Type 1 and 2 cause epidemics during fall,
specifically by immunofluorescence, ELISA alternate year pattern.
or other immunologic techniques. - Type 3 all seasons
- Rapid viral diagnosis by IF or ELISA of - Second cause of LRTI in young children
nasopharyngeal washes, aspirates and - Type 1 – most frequent cause of croup
nasopharyngeal swabs(less satisfactorily) - Type 3 – bronchiolitis and pneumonia in
- Serologic diagnosis –comparison of acute infants
and convalescent phase serum specimens - TRANSMISSION: respiratory secretions,
by ELISA, neutralization or complement- person-person contact and by large
fixation tests. droplets.
- INCUBATION period: 3-6 days
Treatment:
Pathogenesis:
- URTI : alleviation of symptoms
- LRTI: hydration, suctioning of secretions - immunity w/ serotypes 1 and 2 is
and admin. Of humidified oxygen and mediated by local IgA antibodies in the
anti-bronchospastic agents. respiratory tract.
- Severe hypoxia: intubation and - Passively acquired serum neutralizing
ventilatory assistance antibodies also confer some protection
- Infants w/ RSV infection : aerosolized against infection w/ types 1 and 2
Ribavirin has beneficial effect on LRTI - T-cell mediated immunity also be impt in
including alleviation of Blood-gas parainfluenza virus infections.
abnormalities.
- Aerosolized Ribavirin recommended for Clinical Manifestations:
infants who are severely ill, at risk for
complications of RSV ( premature, born - occur most frequently among children,
w/CHD, bronchopulmonary dysplasia, initial infection w/ serotypes 1,2 or 3.
associated w/ acute febrile illness
- present w/ coryza, sore throat, - Some adenovirus types can induce
hoarseness and cough. oncogenic transformation and tumor
- Severe croup: fever persists w/ worsening formation observed only in rodents.
coryza and sore throat.
- Brassy or barking cough progress to frank Epidemiology:
stridor.
- Recover next 1-2 days. - affect infants and children
- Bronchiolitis and pneumonia develops: - infections occur throughout the year.
progressive cough accompanied by - Types 1, 2, 3 and 5 are the most frequent
wheezing, tachypnea, and intercostal isolates from children.
retractions. - Serotypes 4 and 7 and also 3, 14 and 21
- PE: nasopharyngeal discharge and associated w/ outbreaks of ARD in
oropharyngeal injection, along with military recruits in winter and spring.
rhonchi, wheezes, or coarse breath - TRANSMISSION: inhalation of aerosolized
sounds. virus, by inoculation of virus into
- Chest xrays: air trapping and occasionally conjunctival sac and probably the fecal-
interstitial infiltrates. oral route
- Older children and adults: common cold
or as hoarseness w/ or w/o cough. Clinical Manifestations:
- Severe, prolonged and even fatal
parainfluenza infection reported in Children
children and adults w/ severe - most common : acute URTI w/ prominent
immunosuppression including bone- rhinitis
marrow and solid-organ transplant - on occasion LRTI includes bronchiolitis
recipients. and pneumonia develops
- adeno types 3 and 7 cause
Laboratory findings and diagnosis: pharyngoconjuctival fever, a
characteristic acute febrile illness of
- specific diagnosis: detection of virus in children that occurs in outbreaks, most
respiratory tract secretions, throat swabs often in summer camps.
or nasopharyngeal washings. - Syndrome marked by bilateral
- Viral growth in tissue cultures is detected conjunctivitis : bulbar and palpebral
either by hemmaglutination or by conjuctiva have a granular appearance.
cytopathic effect. - Low grade fever present for first 3-5 days
- Rapid viral diagnosis: identification of and rhinitis, sore throat, and cervical
parainfluenza antigens in exfoliated cells adenopathy develop.
from the respiratory tract with IF or ELISA - Illness lasts for 1-2 weeks and resolves
- Highly specific and sensitive: PCR assays spontaneously.
- Serologic diagnosis: hemmaglutinin Adults
inhibition, neutralization of acute and - types 4 and 7 in military recruits
convalescent phase specimens or - prominent sore throat and the gradual
complement-fixation tests. onset of fever w/c often reaches 390C on
2nd or 3rd day of illness
Treatment: - cough is almost always present and
coryza and regional lymphadenopathy are
- Complications such as sinusitis, otitis or frequently seen
superimposed bacterial bronchitis - PE: pharyngeal edema, injection and
develop : Antibiotics should be admin. tonsillar enlargement w/ little or no
- Mild cases: bed rest and moist air exudates.
generated by vaporizers. If pneumonia has developed,
- Severe cases: hospitalization and closed auscultation and x-ray of the chest may
observation. indicate areas of patchy infiltration.
- Acute respiratory distress: humidified - adenovirus associated w/ non-respiratory
oxygen and intermittent racemic tract disease
epinephrine o types 40 and 41 – acute diarrheal illness
- Aerosolized or systematically in young children
administered glucocorticoids are o types 11 and 21 – hemorrhagic cystitis
beneficial.
o types 8, 19 and 37 – epidemic
keratoconjunctivitis associated w/
contaminated ophthalmic solutions and
Adenovirus Infections
roller towels.
- Bone marrow transplant recipients –
Etiologic Agent:
adeno manifested as pneumonia.
Hepatitis, nephritis colitis, encephalitis
- complex DNA viruses measure 70-80 nm in
and hemorrhagic cystitis
diameter
- Solid-organ transplant recipients –
- Genus Mastadenovirus w/ 51 serotypes
hepatitis in liver transplants and nephritis
- Icosahedral shell composed of 20
in renal transplants.
equilateral triangular faces and 12
- AIDS can be affected due to low CD4+ cell
vertices.
counts
- Capsid consists of hexon subunits w/
- Adenovirus nucleic acids has been
group-specific and type-specific antigenic
isolated in myocardial cells from patients
determinants and penton subunits at each
w/ “idiopathic” myocardiomyopathies.
vertex primarily containing group-specific
antigens.
Laboratory Findings and Diagnosis:
- Human adenoviruses have 6 subgenera ( A
thru F) based on homology of DNA
- Adenovirus infection can’t be
genomes and other properties.
differentiated from other viral respiratory
- Linear double-stranded DNA that codes
agents and Mycoplasma pneumoniae.
for structural and non-structural
- Definitive diagnosis: tissue culture ( as
polypeptides.
evidenced by cytopathic changes) , IF and
- Replicative cycle of adenovirus result in
other immunologic techniques.
either lytic infection of cells or in
- Rapid viral diagnosis: IF or ELISA by
establishment of a latent infection
nasopharyngeal aspirates, conjunctival or
(lymphoid cells)
respiratory secretions, urine or stool.
- Highly specific and sensitive PCR assays or
nucleic acid hybridization.
- Adeno type 40 and 41 associated with
diarrheal disease in children require
special tissue-culture cells for isolation. It
is commonly detected by direct ELISA of
stool.

Treatment:

- only symptom-based therapy and


supportive therapy are available
- Ribavirin and cidofivir have activity in
vitro against adenoviruses and anecdotes
of their use in disseminated infection
have been reported.

Prevention:

- Live vaccines against types 4 and 7 and


have been used to control illness in
military recruits.
- It consists of live, unattenuated virus
administered in enteric-coated capsules.

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