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					CHAPTER 178 – COMMON VIRAL RESPIRATORY INFECTIONS                           Psychologically defined “stress” – may contribute
AND SEVERE ACUTE RESPIRATORY SYNDROME (SARS) p.1059-                         to development of symptoms
1065                                                                        Neutralizing antibodies to multiple serotypes by
                                                                             adulthood, although the presence of antibody to
General Conditions                                                           one serotype varies
       Acute viral respiratory illnesses- among most common                Multiple serotypes circulate simultaneously and no
        cause of human diseases, about ½ or more of acute                    single serotype or group of serotypes has been
        illnesses                                                            more prevalent than the others
       Incidence in US – 3-5.6 cases/ person/yr                        Pathogenesis
       Highest among children <1 yr old, remains high til                  Infect cells through attachment to specific cellular
        6y.o., then a progressive decline begin                              receptors (ICAM-1 , LDL-r)
       Adults: 3-4 cases/person/yr                                         Nasal mucosa is edematous, hyperemic, during
       Morbidity: 30-50% time lost from work by adults; 60-                 acute illness, covered by mucous discharge
        80% lost from school by children                                    Mild infiltrate with inflammatory cells
       Use of anti-bacterial agents for viral respiratory                   (neutrophils, lymphocytes, plasma cells,
        infections – major source of drug abuse                              eosinophils)
       2/3 – ¾ of acute respiratory illness – caused by viruses            Hyperactive mucus-secreting glands in the
       URT- involved but LRT involved in lower age groups                   submucosa, engorged nasal turbinates leading to
       Divided into multiple distinct syndromes – “common                   obstruction of openings of sinus cavities
        cold”, pharyngitis, croup (laryngotrachebronchitis),                Mediators linked to S/Sx – bradykinin,
        tracheitis, bronchiolitis, bronchitis, and pneumonia                 lysylbradykinins, histamine, prostaglandin, IL- 1,
       Croup – occurs in very young children and a                          6, 8
        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
       Refer Table 170-1                                                    of subsequent infection and illness
       Most respiratory viruses could cause more than one              Clinical Manifestation
        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
       Clinical illnesses induced by the viruse are rarely                  by 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-                    May cause exacerbations of asthma and chronic
             enveloped, ssRNA, acid-labile, completely                       pulmonary disease in adults
             inactivated at pH < 3                                          Complications such as otits media, acute sinusitis
            Grow preferentially at 33 – 34 C – tem of human                In bonemarrow transplant patients, fatal
             nasal passages rather than at higher temp (37 C)                pneumonias may develop
             of LRT                                                     Diagnosis
            102 distinct serotypes are recognized; 91 – use                Etiologic diagnosis cannot be made on clinical
             ICAM-1 as a cellular receptor and comprise the                  grounds alone
             “major” receptor; 10 – use the LDL receptor                    Diagnosed by isolation of the virus from nasal
             comprises the “minor” receptor group; 1 uses a                  washes or secretions in tissue culture but this is
             sialoprotein cellular receptor                                  rarely undertaken due to the benign course of
        Epidemiology                                                         illness
            Major cause of common cold and isolated from 15-               PCR is more sensitive but done in research
             40% of adults with common-cold like illnesses                   procedure
            Over-all rates of infection are higher among                   Diagnosis by serum antibody impractical due to
             infants and young children and decreases with                   many serotypes present
             increasing age                                                 WBC count and ESR not helpful
            Occur throughout the year, with seasonal peaks in          Treatment
             early fall and spring in temperate climates.                   Treatment is not necessary
            Introduced into families by pre-school or grade-               In patients with pronounced Sx, 1st generation
             school children <6 years old                                    anti-histamines and NSAIDS beneficial; oral
            25-70% - of initial illnesses in family settings are            decongestant if nasal obstruction is present
             followed by secondary causes. With highest attack              Anti-bacterial agents if with bacterial
             rates among youngest siblings at home                           complications such as otitis media, sinusitis
            Attack rates also increase with family size                Prevention
            Spreads through direct contact with infected                   Interferon sprays effective but local nasal
             secretions usually respiratory droplets                         irritation occurs
            Hand-to-hand contact with subsequent self-                     Experminetal vaccines with questionable results
             inoculation of the conjunctival or nasal mucosa.               Antibodies to ICAM-1 not effective
            Transmission by large or small particle aerosol was            Handwashing, environmental decontamination,
             demonstrated                                                    protection against autoinoculation help reduce
            Viruses can be recovered from plastic surfaces                  rates of transmission
             inoculated 1 – 3h previously suggesting
             environmental surfaces contribute to transmission      CORONA VIRUS INCLUDING SARS
            In married couples in which neither partner had
             detectable serum antibody, transmission was            Etiologic Agent
             associated with prolonged contact (>122h) during               Pleomorphic, ssRNA, measures 100-150nm in dm
             a 7-day period                                                 Crown-like produced by the club-shaped
            Transmission is infrequent unless virus is                      projections that stud the viral envelope
             recovered fro the donor’s hands and and nasal                  Group I (HCoV-229E) and Group II (HCoV-OC43)
             mucosa at least 1000 TCID50 of virus was present                infects humans
             in nasal washes from the donor, and the donor was              SARS (SARS-CoV) – shows minimal variation
             at least moderately symptomatic with “cold”                    Difficult to cultivate in vitro, grows only human
            Exposure to cold temeperature, fatigue, sleep                   tracheal organ cultures rather than in tissue
             deprivation not associated with increased rates of              culture
        Except SARS-CoV- grows in African green monkey            Elevated aminotransferases, creatinine kinases,
         kidney (Vero E6)                                           lactate dehydrogenases
Epidemiology                                                       SARS-CoV can be grown from respiratory tract
        Coronavirus infection spread throughout the world          samples by inoculation into Vero E6 tissue culture
        Strains of HCoV-229E and HCoV-OC43                         cells – cytopathic effect can be seen
         demonstrated that serum antibodies acquired               Rapid diagnosis: RT-PCR of respi tract samples and
         early in life and increase in prevalence with              plasma, early in illness, and urine and stool later
         advancing age, so that >80% of adult populations           on
         have antibodies measured by ELISA                         RT-PCR more sensitive than tissue culture but only
        10-35% of common colds caused by coronavirus               1/3 are positive by PCR at initial presentation
        Prevalent in late fall, winter, early spring – times      Serum antibodies can be detected by ELISA or
         when rhinovirus infection are less common                  immunofluorescence, develops detectable serum
        SARS began in Guangdong Province of China in               antibodies within 28d after onset of illness
         November 2002 originated from contact with                Lab dx of corona-virus induced colds is rarely
         semidomesticated animals such as the palm civet            required, but can be detected by ELISA or IF
         or the dog raccoon, animals prized as edible               assays or by RT-PCR
         delicacies that harbor CoV                             Treatment
        Nov16, ’02 – Feb28,’03 : 792 cases of SARS in             No specific therapy for SARS, though ribavirin is
         Guandong                                                   used ut no beneficial effect on the illness
        Healthcare workers and their contacts account for         Glucocorticoids given due to immunopathologic
         most cases                                                 evidence
        Index case that introduce SARS into HK – physician        Supportive care to maintain pulmonary and other
         from Guandong that travelledto HK                          organ system functions – mainstay of therapy
        Similar cases were noted in Singapore, Thailand,          Corona virus induced common colds’ therapy
         Vietnam, Taiwan, and Toronto                               similar with rhinovirus’
        8422 cases identified in 28 countries; 90% occurred    Prevention
         in China and Hongkong                                     Infection control practices, travel advisories,
        Over-asll figure of case-datality rate – 11%               quarantines
        Milder cases in US and in children                        Absence of new cases for 30 days (3x the
        Mechanism of transmission incompletely                     estimated incubation pd of 10d for the disease),
         understood                                                 travel advisories were lifted
        Spread may occur by both large and small aerosols         Strict infection control practices in health care
         and perhaps by fecal-oral route, environmental             facilities
         sources such as sewage and water                          Vaccines against animal CoV, but none yet for
        Individuals may be hyperinfectious or super                human CoV
         spreaders capable of transmitting infection to 10-
         40 contacts, although most infections resulted in          Respiratory Syncytial Virus Infection
         spread either to 1-3 individuals
    Pathogenesis                                                    Etiologic Agent:
        Infect the ciliated epithelial cells in the
         nasopharynx                                            -             RSV member of Paramyxoviridae
        Viral replication leads to damage of ciliated cells        family. Genus Pneumovirus.
         and induction of chemkines and IL, resulting in        -             A single-stranded RNA,
         common cold symptoms                                       enveloped virus ,150-300 nm diameter
        Systemic illness in which virus likely enters the          codes for 11 virus-specific proteins.
         bloodstream, in the urine, and (for up to 2            -             Replication in vitro leads to
         months) in the stool.                                      fusion of neighboring cells into large
        Virus persists in the respiratory tract for 2-3 wks,       multinucleated syncytia.
         and titers peak ~10 days after the onset of            -             Viral RNA contained in a helical
         systemic illness                                           nucleocapsid surrounded by a lipid
        Pulmonary pathology consists of hyaline membrane           envelope bearing 2 glycoproteins: G
         formation, desquamation of pneumocytes in                  protein, virus attaches to the cells, F
         alveolar spaces, and an interstitial infiltrate            (fusion)protein, facilitates entry of virus
         consisting of lymphocytes and mononuclear cells,           into the cell by fusing host and viral
         giant cells are frequently seen, coronavirus               membranes.
         detected in TypeII pneumocytes                         -             Antigenic diversity is reflected
    Clinical Manifestations                                         by difference in G protein while F protein
        2-7 d incubation pd (range is 1-10d)                       is highly conserved.
        Begins as a systemic illness marked by onset of
         fever accompanied by malaise, headache,                    Epidemiology:
         myalgia, and followed in 1-2 days by a non-
         productive cough and dyspnea; 25% have diarrhea        -             major respiratory pathogen of
        CXR showed infiltrates such as patchy areas of             young children
         consolidation, most frequently in peripheral and       -             foremost cause of LRTI in infants
         lower kung field; or interstitial infiltrates          -             occur in winter or spring, late
         progressing to diffuse involvement                         fall and lasts up to 5 mos.
        In severe cases, respiratory function may worsen       -             Highest among infants 1-6 mos of
         during tha 2nd week and progress to ARDS with              age. PEAK: 2-3mos.
         multiorgan dysfunction                                 -             Age 2 - all children will be
        Risk fxs for severity: age >50; comorbidities such         infected
         as CVD, diabetes, hepatitis; pregnancy                 -             Common cold-like syndrome
        Clinical features similar with rhinoviruses                illness – most commonly associated with
        In a study, mean incubation period – 3d, longer            adults.
         than rhinoviruses; duration is shorter, mean of 6-     -              Severe LRTI w/ pneumonitis –
         7; amount of nasal discharge is greater in colds           occur in elderly, immunocompromised
         induced by coronaviruses                                   disorders or tx ( recipients of bone-
        Coronaviruses recovered from infants with                  marrow and solid0organ transplants)
         pneumonia and from military recruits with LRT          -             important nosocomial pathogen
         disease and associated with worsening chronic          -             TRANSMISSION: close contact w/
         bronchitis                                                 contaminated fingers or fomites
                                                                             Self-inoculation of the
    Laboratory Findings and Diagnosis                               conjunctivae or anterior nares
       Lymphopenia in ~50% of cases mostly affecting                        Coarse aerosols produced by
        CD4+ Tcells but also CD8+ Tcells and NK cells               coughing and sneezing
       Total WBC- normal or slightly low;                               -    INCUBATION period: 4-6 days,
        thrombocytopenia as disease develops                        virus shedding last for > 2 weeks in
    children and for shorter periods for adults     -            Aerosolized Ribavirin
    and multiple weeks for                              recommended for infants who are
    immunocompromised patient.                          severely ill, at risk for complications of
                                                        RSV ( premature, born w/CHD,
    Pathogenesis:                                       bronchopulmonary dysplasia, nephrotic
                                                        syndrome or immunosuppression)
-              Severe bronchiolitis or              -            Combined therapy w/
    pneumonia – necrosis of the bronchiolar             aerosolized ribavirin and palivizumab is
    epithelium and a peribronchiolar                    being evaluated in the treatment of
    infiltrate of lymphocytes and                       immunosuppressed patients w/ RSV
    mononuclear cells.                                  pneumonia.
-              interalveolar thickening and
    filling of alveolar spaces w/ fluid can be          Prevention:
    also found.
-              Studies indicate that the            -            RSVIg or palivizumab approved
    presence of nasal IgA neutralizing                  as prophylaxis against RSV for children < 2
    antibody correlates more closely w/                 yrs of age who have bronchopulmonary
    protection than the presence of serum               dysplasia or were born prematurely.
                                                        Metapneumovirus Infections
    Clinical Manifestations:
                                                    -            viral respiratory pathogen of
-             Infants - LRT involvement                 Paramyxoviridae family Genus
    includes pneumonia, bronchiolitis and               Metapneumovirus
    tracheobronchitis.                              -            morphology and genomic
    -                   begins most frequently          organization similar to respi pathogen of
    w/ rhinorrhea, low-grade fever and mild             turkeys
    systemic symptoms often accompanied by          -            spherical, filamentous or
    cough and wheezing.                                 pleomorphic in shape and measure 60-280
           - Recover gradually over 1-2                 nm in diameter.
    weeks.                                          -            Initially detected in nasal
    -                SEVERE illness in                  aspirates
    premature, born w/CHD,                          -            Most frequent during winter and
    bronchopulmonary dysplasia, nephrotic               occur early in life. Serum antibodies to
    syndrome or immunosuppression.                      the virus are present in nearly all children
    Tachypnea and dyspnea develop and                   by age 5.
    eventually frank hypoxia, cyanosis and          -            Detected thru nasal aspirates
    apnea ensue.                                        and respi secretions by PCR or by growth
           - PE: diffuse wheezing, rhonchi              in rhesus monkey kidney tissue cultures.
    and rales.                                      -            Serologic diagnosis made by
    -                Chest radiography:                 ELISA w/c utilizes HMPV-infected tissue
    hyperexpansion, peribronchial thickening            culture lysates as sources of antigens.
    and variable infiltrates ranging from
    diffuse interstitial infiltrates to segmental       Parainfluenza Virus Infections
    or lobar consolidation.
-             Adults – common cold, w/                  Etiologic Agent:
    rhinorrhea, sorethroat, and cough.
           - associated w/ moderate                 -            belong to Paramyxoviridae
    systemic symptoms such as malaise,                  family Genus Respirovirus and Rubulavirus
    headache and fever.                             -            150-200 nm in diameter,
-             cause of morbidity and mortality          enveloped and single stranded RNA
    in patients undergoing bone marrow and              enclosed in helical nucleocapsid and
    solid-organ transplantation                         codes for six structural and several
-             sinusitis, otitis media and               accessory proteins.
    worsening of chronic obstructive and            -            studded w/ 2 glycoproteins: both
    reactive airway disease associated w/RSV            hemagglutinin and neuraminidase activity
    infection.                                          and other fusion activity

    Lab findings and Diagnosis:                         Epidemiology:

-            isolated in tissue culture and         -              type 4 difficult to grow in tissue
    identified specifically by                          cultures
    immunofluorescence, ELISA or other              -            infxn acquired early childhood,
    immunologic techniques.                             by age 5 most children have antibodies to
-            Rapid viral diagnosis by IF or             serotypes 1,2 and 3.
    ELISA of nasopharyngeal washes,                 -            Type 1 and 2 cause epidemics
    aspirates and nasopharyngeal swabs(less             during fall, alternate year pattern.
    satisfactorily)                                 -            Type 3 all seasons
-            Serologic diagnosis –comparison        -            Second cause of LRTI in young
    of acute and convalescent phase serum               children
    specimens by ELISA, neutralization or           -            Type 1 – most frequent cause of
    complement-fixation tests.                          croup
                                                    -            Type 3 – bronchiolitis and
    Treatment:                                          pneumonia in infants
                                                    -            TRANSMISSION: respiratory
-            URTI : alleviation of symptoms             secretions, person-person contact and by
-            LRTI: hydration, suctioning of             large droplets.
    secretions and admin. Of humidified             -            INCUBATION period: 3-6 days
    oxygen and anti-bronchospastic agents.
-            Severe hypoxia: intubation and             Pathogenesis:
    ventilatory assistance
-            Infants w/ RSV infection :             -            immunity w/ serotypes 1 and 2 is
    aerosolized Ribavirin has beneficial effect         mediated by local IgA antibodies in the
    on LRTI including alleviation of Blood-gas          respiratory tract.
    abnormalities.                                  -            Passively acquired serum
                                                        neutralizing antibodies also confer some
        protection against infection w/ types 1        -             Capsid consists of hexon subunits
        and 2                                              w/ group-specific and type-specific
-                T-cell mediated immunity also             antigenic determinants and penton
        be impt in parainfluenza virus infections.         subunits at each vertex primarily
                                                           containing group-specific antigens.
        Clinical Manifestations:                       -             Human adenoviruses have 6
                                                           subgenera ( A thru F) based on homology
    -             occur most frequently among              of DNA genomes and other properties.
        children, initial infection w/ serotypes       -             Linear double-stranded DNA that
        1,2 or 3. associated w/ acute febrile              codes for structural and non-structural
        illness                                            polypeptides.
    -             present w/ coryza, sore throat,      -             Replicative cycle of adenovirus
        hoarseness and cough.                              result in either lytic infection of cells or
    -             Severe croup: fever persists w/          in establishment of a latent infection
        worsening coryza and sore throat.                  (lymphoid cells)
    -             Brassy or barking cough progress     -             Some adenovirus types can
        to frank stridor.                                  induce oncogenic transformation and
    -             Recover next 1-2 days.                   tumor formation observed only in
    -             Bronchiolitis and pneumonia              rodents.
        develops: progressive cough accompanied
        by wheezing, tachypnea, and intercostal            Epidemiology:
    -             PE: nasopharyngeal discharge         -            affect infants and children
        and oropharyngeal injection, along with        -            infections occur throughout the
        rhonchi, wheezes, or coarse breath                 year.
        sounds.                                        -             Types 1, 2, 3 and 5 are the most
    -             Chest xrays: air trapping and            frequent isolates from children.
        occasionally interstitial infiltrates.         -             Serotypes 4 and 7 and also 3, 14
    -             Older children and adults:               and 21 associated w/ outbreaks of ARD in
        common cold or as hoarseness w/ or w/o             military recruits in winter and spring.
        cough.                                         -             TRANSMISSION: inhalation of
    -             Severe, prolonged and even fatal         aerosolized virus, by inoculation of virus
        parainfluenza infection reported in                into conjunctival sac and probably the
        children and adults w/ severe                      fecal-oral route
        immunosuppression including bone-
        marrow and solid-organ transplant                  Clinical Manifestations:
        Laboratory findings and diagnosis:             -            most common : acute URTI w/
                                                           prominent rhinitis
    -             specific diagnosis: detection of     -            on occasion LRTI includes
        virus in respiratory tract secretions,             bronchiolitis and pneumonia develops
        throat swabs or nasopharyngeal washings.       -            adeno types 3 and 7 cause
    -             Viral growth in tissue cultures is       pharyngoconjuctival fever, a
        detected either by hemmaglutination or             characteristic acute febrile illness of
        by cytopathic effect.                              children that occurs in outbreaks, most
    -             Rapid viral diagnosis:                   often in summer camps.
        identification of parainfluenza antigens       -            Syndrome marked by bilateral
        in exfoliated cells from the respiratory           conjunctivitis : bulbar and palpebral
        tract with IF or ELISA                             conjuctiva have a granular appearance.
    -             Highly specific and sensitive:       -            Low grade fever present for first
        PCR assays                                         3-5 days and rhinitis, sore throat, and
    -             Serologic diagnosis:                     cervical adenopathy develop.
        hemmaglutinin inhibition, neutralization       -            Illness lasts for 1-2 weeks and
        of acute and convalescent phase                    resolves spontaneously.
        specimens or complement-fixation tests.                Adults
                                                       -            types 4 and 7 in military recruits
        Treatment:                                     -            prominent sore throat and the
                                                           gradual onset of fever w/c often reaches
    -             Complications such as sinusitis,         390C on 2nd or 3rd day of illness
        otitis or superimposed bacterial               -            cough is almost always present
        bronchitis develop : Antibiotics should be         and coryza and regional lymphadenopathy
        admin.                                             are frequently seen
    -             Mild cases: bed rest and moist       -            PE: pharyngeal edema, injection
        air generated by vaporizers.                       and tonsillar enlargement w/ little or no
    -             Severe cases: hospitalization and        exudates.
        closed observation.                                              If pneumonia has developed,
    -             Acute respiratory distress:              auscultation and x-ray of the chest may
        humidified oxygen and intermittent                 indicate areas of patchy infiltration.
        racemic epinephrine                            -            adenovirus associated w/ non-
    -             Aerosolized or systematically            respiratory tract disease
        administered glucocorticoids are               o                       types 40 and 41 – acute
        beneficial.                                        diarrheal illness in young children
                                                       o                       types 11 and 21 –
                                                           hemorrhagic cystitis
        Adenovirus Infections                          o                       types 8, 19 and 37 –
                                                           epidemic keratoconjunctivitis associated
        Etiologic Agent:                                   w/ contaminated ophthalmic solutions
                                                           and roller towels.
    -             complex DNA viruses measure          -            Bone marrow transplant
        70-80 nm in diameter                               recipients – adeno manifested as
    -             Genus Mastadenovirus w/ 51               pneumonia. Hepatitis, nephritis colitis,
        serotypes                                          encephalitis and hemorrhagic cystitis
    -             Icosahedral shell composed of 20     -            Solid-organ transplant recipients
        equilateral triangular faces and 12                – hepatitis in liver transplants and
        vertices.                                          nephritis in renal transplants.
-            AIDS can be affected due to low
    CD4+ cell counts
-            Adenovirus nucleic acids has
    been isolated in myocardial cells from
    patients w/ “idiopathic”

    Laboratory Findings and Diagnosis:

-             Adenovirus infection can’t be
    differentiated from other viral respiratory
    agents and Mycoplasma pneumoniae.
-             Definitive diagnosis: tissue
    culture ( as evidenced by cytopathic
    changes) , IF and other immunologic
-             Rapid viral diagnosis: IF or ELISA
    by nasopharyngeal aspirates, conjunctival
    or 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


-             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.


-             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

                          ---AYKA/ ZIZO---