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Respiratory Tract Infection Faculty Copy – Page 1
VIROLOGY CASE-BASED SMALL GROUP
DISCUSSION
SESSION 23
RESPIRATORY TRACT INFECTIONS
THURSDAY, MARCH 22, 2001
1:00PM – 3:00PM
Reading Assignment:
Sherris Medical Microbiology, Chapters 32, 37
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CASE HISTORY 1
The patient was a 4-month-old female with congenital heart disease who was admitted
to the hospital in January with severe respiratory distress. Five days prior to admission
she had developed a cough and rhinitis. Two days later she began wheezing and was
noted to have a fever. She was brought to the emergency room when she became
lethargic.
One sibling was reported to be coughing, and her father had a "cold". On examination
she was agitated and coughing. She had a fever of 38.9 0C, tachycardia with a pulse of
220, tachypnea with respirations of 80/min., and a blood pressure of 90/58 mm Hg.
Her fontanelles were open, soft, and flat. Her throat was clear. She had subcostal
retractions and nasal flaring. On auscultation of her lungs, there were rhonchi as well
as inspiratory and expiratory wheezes.
A chest radiograph revealed interstitial infiltrates and hyperexpansion. Arterial blood
gases on supplemental oxygen revealed respiratory acidosis with relative hypoxemia.
She was put in respiratory isolation in the pediatric intensive care unit and was
subsequently intubated. Blood and nasopharyngeal cultures were obtained and sent to
the bacteriology and virology laboratories. A nasopharyngeal wash specimen was
positive for RSV antigen by rapid test and specific antiviral therapy was begun. She
was extubated 5 days later and discharged home on day 8.
BACKGROUND
This patient was found to be infected with RSV (a negative strand RNA virus),
which causes severe infections in children less than 1 year old, whereas
reinfections in older children and adults may result in minimal respiratory tract
symptoms. RSV can also cause acute laryngotracheobronchitis. The elderly may
also develop severe RSV infections.
The differential diagnosis for this patient's pneumonia includes respiratory
viruses such as parainfluenza virus types 1, 2 and 3, influenza A and B viruses,
and respiratory syncytial virus (RSV). Bordetella pertussis could also have
caused her illness.
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1.
What type of isolation should the patient be put in?
Transmission is via contact with respiratory droplets. Because RSV can
cause nosocomial infections, patients should be put in contact isolation. If
patients are not isolated and infection control practices (strict handwashing, use of gloves and gowns, etc.) are not used, cross-infections can
occur at a rate of 20 to 50%. Several patients with RSV can be "cohorted"
(put in the same room), and their health care providers can be similarly
cohorted. Nosocomial RSV infections are a hazard particularly for other
hospitalized patients with congenital heart disease, lung disease, or
immunodeficiency states who are at risk for life-threatening RSV
infections.
Community outbreaks of RSV infection occur annually and can commence
at any time from late fall to early spring. The usual outbreak lasts 8 to 12
weeks and can involve nearly one half of all families with children. In the
family setting, it appears that older siblings often introduce the virus into
the home, and secondary infection rates can be almost 50%. The usual
duration of virus shedding is 5 to 7 days; young infants, however, may
shed virus for 9 to 20 days or longer.
2.
What is known about the pathogenesis of the infection?
The virus is spread to the upper respiratory tract by contact with infective
secretions. Infections appear to be confined primarily to the respiratory
epithelium, with progressive involvement of the middle and lower airways.
Viremia occurs rarely.
The virus particles are also toxic to tissues. This toxicity can be
demonstrated by inoculating high concentrations of inactivated virions
into mice, which produces acute inflammatory changes in the absence of
viral penetration or replication within cells.
The apparent enhanced severity of disease, particularly in very young
infants, is not yet clearly understood, but may have an immunologic basis.
Factors that have been proposed to play a role include (1) qualitative or
quantitative deficits in humoral or secretory antibody responses to critical
virus-specified proteins; (2) excessive damage from inflammatory
cytokines or direct cell-mediated cytotoxicity; (3) formation of antigen-
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antibody complexes within the respiratory tract resulting in complement
activation; and (4) IgE-mediated histamine release.
The usual mortality among infants hospitalized with RSV infections is 0.5
to 1%; however, this rises to 15% or greater in children receiving cancer
chemotherapy, infants with congenital heart disease, and those with
severe immunodeficiency. Infants with underlying chronic lung disease
are also considered to be at high risk for a lethal outcome. Former
premies are also high risk-tend to have bronchopulmonary displasia from
prolonged ventillation.
3.
Describe the rapid test used for detection of RSV.
Rapid antigen detection tests are currently available for RSV and influenza
A. RSV can be detected in nasopharyngeal washings or aspirates by either
an enzyme immunoassay (EIA) or immunofluorescence. Many institutions
are replacing immunofluorescence with EIA because EIA is easier to
perform, is more rapid when multiple specimens must be tested, and has
similar sensitivity and specificity. RSV isolation in cell culture takes 3 to
10 days. The advantage of culture is a higher degree of sensitivity than
that of rapid procedures, and culture has the ability to detect a variety of
viral agents. However, specimens for RSV culture must be quickly
transported and cultured because this virus soon loses infectivity outside
the host. Rapid viral antigen tests are valuable because of the length of
time required to detect many viruses in culture. Prompt results are
preferred so that the decision to use antiviral agents can be made as soon
as possible.
4.
A formalin fixed-killed virus vaccine was tested against RSV. Why was this
vaccine discontinued?
This vaccine was discontinued because it predisposed children to more
severe disease!
5.
Describe the preventative therapy currently in use for selected infants.
Palivizumab and RespiGam are currently used to prevent RSV infection in
high risk infants.
Only one antiviral agent, ribavirin, is available for treatment of RSV in
infants. It has been shown to decrease viral shedding and may increase
the patient's oxygenation. It is delivered by aerosol to best reach the site
of infection and to minimize toxicity. It is generally only given to the
highest risk patients because of its extreme cost (>$1000/day).
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Ribavirin is a nucleoside analogue and is thought to inhibit the viral RNAdependent RNA polymerase.
6.
Is this child likely to be reinfected?
Yes. Immunity is short-lived and multiple reinfections are possible.
However, subsequent disease is generally less severe.
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CASE HISTORY 2
The patient was a 1-year-old male who was brought to the clinic in January because he
developed fever, chest congestion, rhinorrhea, decreased oral intake and a "barking"
cough 3 days previously.
His medical history was significant only for recurrent otitis media. On examination, his
temperature was 38.40C. He was in no acute distress and had audible obstructive
upper airway sounds. His throat was erythematous. On lung examination, upper
airway sounds were prominent and there was no wheezing or subcostal retractions.
The clinical impression was that he had croup. Specimens were sent for viral cultures.
He was managed with therapies for symptomatic relief including the use of a humidifier
in the home. Ten days later parainfluenza was identified from a nasopharyngeal
specimen only after hemadsorption studies were done on the virus culture.
BACKGROUND
This patient's clinical diagnosis was croup (acute
laryngotracheobronchitis).
This patient was infected with parainfluenza virus type 1 (PIV-1). PIV is
the virus most commonly associated with croup. There are four
serotypes of PIV, PIV-1 to PIV-4. Like influenza virus, PIV produces both
hemagglutinins and neuraminidase. Unlike influenza virus, PIV has a
nonsegmented genome and the four types are antigenically stable. RSV
can cause a similar clinical syndrome to PIV.
1.
How is the virus transmitted?
Transmission is via direct inhalation of particles or contact with
contaminated secretions to nasal or conjunctival epithelium.
Parainfluenza is a disease seen primarily in children 4 months to 6
years of age. Epidemic disease occurs in the fall with PIV-1 or PIV-2
predominantly in alternate years. PIV-3 appears to be endemic
throughout the year. Like all enveloped respiratory viruses, PIV is
spread most efficiently by aerosolization.
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2.
What is croup? Why don’t adults get croup?
The pathophysiology of croup is due to infection and inflammation in the
subglottic area. This leads to a stridorous cough. Manifestations of
parainfluenza virus infections are generally more severe in infants and
young children than in adults. (adult have a larger subglottic area and
therefore the inflammation does not lead to as severe a cough). Infection
can result in severe pneumonia, bronchitis, laryngitis, croup
(laryngotracheobronchitis), or just a mild upper respiratory tract infection.
There are no extrapulmonary manifestations (no viremia).
3.
Describe how the clinical diagnosis of croup was confirmed. Is laboratory
confirmation critical in all cases?
Laboratory confirmation is not critical in cases with “classic” clinical
presentation.
There is attached a copy of the procedure for working up respiratory
specimens.
4.
Is this child likely to be re-infected? What is the common symptom in adults with
this infections?
Yes. Immunity is only transient. Repeat infections, which are usually
milder, occur in older children and adults.
5.
If this child had more severe croup, what treatment would be appropriate?
Recent studies indicate that in children with moderately severe croup,
treatment with intramuscular dexamethasone or nebulized budesonide
resulted in more rapid clinical improvement than did the administration of
placebo, with dexamethasone offering the greatest improvement.
Treatment with either glucocorticoid resulted in fewer hospitalization.
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CASE HISTORY 3
A 16 year-old white female presents with a two week history of sore throat and lethargy.
The patient was previously healthy. She had fever to 103 o F. for a few days, and saw
her physician, who noted exudate and obtained a throat culture, which was negative for
group A streptococcus. Her physician prescribed ampicillin for her symptoms, and after
taking several doses, she developed a diffuse macular rash on her trunk and
extremities. The question of penicillin allergy arose. She comes to your office because
she reports that she still has low grade fever, some sore throat, and feels extremely
tired and listless. Physical examination reveals an erythematous pharynx with white
exudates on the tonsils, and cervical, axillary, and inguinal adenopathy. Abdominal
examination reveals a palpable spleen tip. A blood count reveals a WBC of 12.0 with
20 neutrophils, 5 bands, 30 lymphocytes, 30 atypical lymphocytes which are not blasts,
and 15 monocytes. Hemoglobin and platelet count are normal. A monospot test is
reported as positive.
STUDY QUESTIONS
1.
How is the virus transmitted?
EBV is transmitted by close contact with respiratory secretions; it is
frequently referred to as “the kissing disease.”
2.
What is a monospot test and what other laboratory tests may be useful in
confirming your preliminary diagnosis?
The monospot test detects the presence of heterophile antibody (human
serum which will agglutinate sheep red blood cells). This is IgM antibody,
and appears during the first or second week of illness, persisting for
several months. Many conditions can produce heterophile antibodies, but
specific absorption studies allow for specificity of the test for infectious
mononucleosis (ie the reaction occurs if the serum is absorbed first with
guinea pig kidney antigens, but not if the serum is absorbed first with beef
red blood cells-other illnesses will be associated with other absorption
patterns). The monospot is an insensitive test in young children. Some
false-positive reactions may occur in adolescents and adults. If a more
specific test is desired, serum can be tested for IgM and IgG antibodies to
EBV viral capsid antigen (VCA).
3.
What are the long-term consequences of infection?
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Most individuals have no long-term consequences following EBV infection.
Many infections in normal hosts are asymptomatic. Immunocompromised
patients may develop long-term sequelae. Transplant patients may
develop an EBV-associated lymphoproliferative disease. Individuals with
X-linked lymphoproliferative syndrome cannot mount a normal immune
response to EBV, and EBV infection in these individuals may be fatal.
Patients with AIDS may develop several EBV-associated disorders: nonHodgkin lymphoma, lymphocytic interstitial pneumonitis, and oral “hairy”
leukoplakia. Several malignancies have been associated with EBV
infection: Burkitt lymphoma, nasopharyngeal carcinoma, and possibly
Hodgkin disease. EBV has not been proved to be associated with “chronic
fatigue syndrome.”
4
Are there any effective anti-viral agents that act against this virus?
Acyclovir and ganciclovir act on the lytic phase of EBV replication, but not
the latent phase, inhibiting EBV DNA polymerase and subsequent viral
production. These drugs share no effect on the clinical course of
infectious mononucleosis and therefore should not be prescribed for this
condition. Acyclovir therapy has been reported to result in regression of
oral “hairy” leukoplakia lesions.
5.
Is your patient likely to be re-infected? Are family members at risk for infection?
What other contacts are likely to be infected?
Recurrent infection has not been well-documented, if it occurs at all.
Family members are at risk of infection if they share oral secretions. Other
individuals who may become infected are the patient’s boyfriend, due to
sharing the oral secretions during kissing.
6.
Why did the patient have a rash after Ampicillin? Should you tell her that she is
allergic to the drug?
Ampicillin and other penicillin derivatives frequently are associated with
rash when given to patients with infectious mononucleosis. This is a
classic association which may provide a clue to the diagnosis. The exact
basis for this reaction is unclear, but it is known that it does not represent
a hypersensitivity reaction to the drug, which can be safely given to the
patient after the infectious mononucleosis illness has resolved.
7.
What other pathogens besides EBV can result in an infectious mononucleosis
illness?
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Cytomegalovirus, Toxoplasma gondii, and acute HIV infection can also
cause infectious mononucleosis-type illnesses. Also mention Acute
EBV hepatitis followed by the appearance of local and humoral antibody
along with an evolving, more durable cellular immunity. Finally, there is
repair of tissue damage.
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CASE HISTORY 4
A 75 year-old female residing in a nursing home developed the sudden onset of fever
to 101o F, headache and malaise in December. Over the next two days, she had
increasing difficulty breathing and was transferred to a medical facility where a
diagnosis of pneumonia was made by chest x-ray. Her 2 year old grandson had visited
her three days prior to the onset of symptoms. He became ill the day after the visit with
cough, rhinorrhea and vomiting. The woman had not received an influenza vaccine that
year; her physician deferred the vaccine because the patient had an upper respiratory
infection. The woman was treated with antibiotics and oxygen. She gradually
recovered. After she was discharged, the clinical virology laboratory isolated influenza B
virus from a pharyngeal swab.
BACKGROUND
Influenza B virus (a negative strand RNA virus with a segmented genome).
Influenza viruses have a predilection for the respiratory tract, and viremia is
rarely detected. They multiply in ciliated respiratory epithelial cells, leading to
functional and structural ciliary abnormalities. This is accompanied by a switchoff of protein and nucleic acid synthesis in the affected cells, the release of
lysosomal hydrolytic enzymes, and desquamation of both ciliated and mucusproducing epithelial cells. There is, thus substantial interference with the
mechanical clearance mechanism of the respiratory tract. The process of cell
death results in the cleavage of complement components, leading to localized
inflammation. Early in infection, the primary chemotactic stimulus is directed
toward mononuclear leukocytes, which constitute the major cellular inflammatory
component. The respiratory epithelium may not be restored to normal for 2 to 10
weeks after the initial insult.
The virus particles are also toxic to tissues. This toxicity can be demonstrated by
inoculating high concentrations of inactivated virions into mice, which produces
acute inflammatory changes in the absence of viral penetration or replication
within cells.
Other host cells functions are also severely impaired, particularly during the
acute phase of infection. They include chemotactic phagocytic, and intracellular
killing functions of polymorphonuclear leukocytes and perhaps of alveolar
macrophage activity.
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The net result of these effect, is that on entry into the respiratory tract, the
viruses cause cell damage, especially in the respiratory epithelium, which elicits
an acute inflammatory response and impairs mechanical and cellular host
responses. This damage renders the host highly susceptible to invasive bacterial
superinfection. In vitro studies also suggest that bacterial pathogens such as
staphylococci can more readily adhere to the surfaces of influenza virus-infected
cells. Recovery from infection begins with interferon production, which limits
further virus replication, and with rapid generation of natural killer cells. Shortly
thereafter, class I major histocompatibility complex (MHC)-restricted cytotoxic T
cells appear in large numbers to participate in the lysis of virus-infected cells
and,
thus,
in
initial
control
of
the
infection.
This
is
followed by the appearance of local and humoral antibody along with an evolving,
more durable cellular immunity. Finally, there is repair of tissue damage.
1.
How is the virus transmitted?
Inhalation or contact with respiratory secretions from an infected person.
2.
How is the viral infection detected?
During the acute phase of illness, influenza viruses can be readily isolated
from respiratory tract specimens, such as nasopharyngeal and throat
swabs. Most strains grow in primary monkey kidney cell cultures or in the
amniotic cavity of embryonated hen's eggs, and they can be detected by
hemadsorption or hemagglutination. Rapid diagnosis of infection is
possible by direct immunofluorescence or immunoenzymatic detection of
viral antigen in epithelial cells or secretions from the respiratory tract.
Serologic diagnosis is of considerable help epidemiologically and is
usually made by demonstrating a fourfold or greater increase in
complement-fixing or hemagglutination inhibition antibody titers in acute
and convalescent specimens collected 10-14 day apart.
3.
The woman received a vaccine last year, why wasn’t she still protected? Is a
URI a contraindication to vaccination?
The best available method of control is by use of killed viral vaccine
prepared from those strains related most closely to the antigenic subtypes
currently causing infections. (Viral strains change each year due to
antigenic drift and shift). These inactivated vaccines may contain whole
virions or "split" subunits composed primarily of hemagglutinin antigens.
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They are commonly used, in two doses given 1 month apart, to immunize
children who may not have been immunized previously; otherwise, single
annual doses are recommended just prior to influenza season. Used in
this way, the virus vaccines may be 70 to 85% effective.
It is recommended that vaccination be directed primarily toward the
elderly, individuals of all ages who are at high risk (eg, those with chronic
lung or heart disease), and their close contacts, including medical
personnel and household members.
A URI is not contraindication for vaccination.
4.
Are there any effective anti-viral agents that act against this virus?
Yes. Oseltamivir and zanamivir has been shown to inhibit the replication
of influenza A and B strains in vitro, in mice and in experientally induced
infection in humans. Hayden et al. report that in a double-bind randomized,
placebo-controlled trial conducted over a six-week period during the
influenza season, 75 mg of oseltamivir administered once or twice daily
(for a total dose of 75 or 150 mg daily) was well tolerated, and its efficacy
as prophylaxis against laboratory-documented febrile influenza was 74
percent (95 percent confidence interval, 53 to 88 percent). Once-daily and
twice-daily doses provided similar levels of efficacy. Likewise, Monto et al.
found that another neuraminidase inhibitor, zanamivir, was approximately
84 percent effective (95 percent confidence interval, 55 to 94 percent) in
preventing laboratory-confirmed illness associated with fever. Zanamirvir
is an orally inhaled compound that has been approved for influenza
treatment in Australia, Europe, and the United States.
These specific inhibitors of influenza neuraminidase have been discovered
by analyzing the crystallographic structure of this molecule and applying
the techniques of rational drug design. These compounds bind to the
conserved active site of neuraminidase and appear to inhibit the release of
viruses from infected cells and their subsequent spread to adjacent cells.
The neuraminidase inhibitors for which data are currently available appear
to be effective against both influenza A and influenza B infections. They
seem to have less potential than amantadine or rimantadine for inducing
resistance and are associated with fewer major side effects, but they are
likely to cost more.
Amantadine hydrochloride, a symmetric amine, has been shown to be
effective in short-term (several weeks) oral prophylaxis of Influenza A
INFECTIONS BUT NOT Influenza B. It appears to act by blocking the ion
channel of the viral M2 protein, resulting in interference with its key role in
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early virus uncoating and also later virion assembly. Amantadine can
produce side effects, however, and is recommended only for high-risk
patient until vaccine-induced immunity can be achieved. A typical example
of its use would be during an epidemic in which an elderly, potentially
susceptible patient may become exposed to infection within a defined
period. Oral amantadine prophylaxis may be initiated concurrently with
administration of a vaccine containing the most current continued
protection. It must be emphasized that amantadine has been proven
effective for influenza A virus infections only; it is useless in other
respiratory virus. A newer related drug, rimantadine, seems to be as
efficacious as amantadine and may cause fewer adverse effects.
Unfortunately, virus resistance to both drugs can develop. A single
mutation in the membrane portion of the M2 protein is all that is necessary
for this to occur.
5.
What recommendation would you suggest for this woman for the next flu
season?
She should receive the vaccine each year.
CASE HISTORY 5
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The patient was a 2 ½ year old male, who was admitted to the hospital in August
with fever and respiratory distress. Patient was well until one day before when he
developed fever, rhinorrhea and congestion. On the day of admission, he was
brought to the ER because he seemed to have trouble breathing. His medical
history was significant for developmental delay and numerous episodes of aspiration
pneumonia. Family history revealed that a 7 year-old sibling and several of his
“swim-team” members had pharyngitis and conjunctivitis 10 days ago.
On examination, the child’s temperature was 40.80C. He was tachypnic with a
respiratory rate of 40. The heart rate was 160. He had moderate mucoid nasal
discharge. He had subcostal retractions and nasal flaring. His throat was red and
there was exudate on both tonsils.
On auscultation of his lungs, there were scattered rhonchi, but no wheezes noted. A
chest radiograph revealed no new findings. He was put in respiratory isolation in the
pediatric wards. Blood and nasopharyngeal cultures were sent to the microbiology
laboratory. A nasopharyngeal wash specimen was positive for adenovirus (was
detected by shell vial technique at 480 and confirmed by staining with monoclonal
antibodies).
BACKGROUND
Etiology: Adenoviruses are DNA viruses; at least 51 distinct serotypes divided
into 6 subgenera (A to F) cause human infections.
Human adenovirus infections are ubiquitous. Adenoviruses are most
important clinically because of their capacity to cause acute infections of the
respiratory system and conjunctivae. Adenoviruses cause 5-8% of acute
respiratory disease in infants and children including pneumonia. The
serotype of adenovirus that causes infection and the type of disease induced
is closely related to the age of the patient. (See following table)
The incidence of adenovirus-induced respiratory tract disease is increased
slightly in late winter, spring, and early summer. Enteric disease occurs
during most of the year and primarily affects children younger than 4 years of
age. Adenovirus infections are most communicable during the first few days
of an acute illness, but persistent and intermittent shedding for longer
periods, even months, is frequent. The incubation period for respiratory tract
infection varies from 2 to 14 days; for gastroenteritis, it is 3 to 10 days.
Diseases Caused by Adenoviruses
Group Affected
Neonates
Infants
Children
Young children
Adults
Immunocompromised
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Syndromes
Common Causal
Adenovirus
Serotypes
Fatal disseminated infection
3, 7, 21, 30
Coryza, pharyngitis (most
1, 2, 5
asymptomatic)
Upper respiratory disease
1, 2, 4-6
Pharyngoconjunctival fever
3, 7
Hemorrhagic cystitis
11, 21
Diarrhea
2, 3, 5, 40, 4 1
Intussusception
1, 2, 4, 5
Meningoencephalitis
2, 6, 7, 12
Acute respiratory disease and
3, 4, 7
pneumonia
Epidemic keratoconjunctivitis
8, 19, 37
Pneumonia with dissemination, urinary 5, 31, 34, 35,
tract infection
39, 42-47
CNS disease including encephalitis
7, 12, 32
Types 1, 2, 5 and 6 are frequently isolated from the situ tonsils and
adenoids of young children. The children may be asymptomatic or may
have upper respiratory infection at the time of isolation.
Type 3, 4 and 7 are most frequently isolated from young adults with acute
upper and lower respiratory disease. Military recruits seem particularly
likely to be infected with these agents, as they are to be infected with
mycoplasmal and meningococcal organisms. The reasons for the
increased infection rates are probably related to the crowding of a
susceptible population.
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STUDY QUESTIONS
1.
Describe the modes of adenoviral transmission.
Adenoviruses causing respiratory tract infection usually are transmitted
by respiratory tract secretions through person-to-person contact,
fomites, and aerosols. Because adenoviruses are stable in the
environment, fomites may be important in their transmission. The
conjunctiva can provide a portal of entry. Community outbreaks of
adenovirus-associated pharngonconjunctival fever have been attributed
to exposure to water from contaminated swimming pools and fomites,
such as shared towels. Epidemic keratoconjunctivitis often has been
associated with nosocomial transmission in ophthalmologists’ offices.
Enteric strains of adenoviruses are transmitted by the fecal-oral route.
Nosocomial spread often has resulted from exposure to contaminated
hands of health care workers and infected equipment, including
pneumotonometers and opthalmologic solutions.
2.
Describe the clinical manifestations of adenoviral infections.
The most common site of adenovirus infection is the upper respiratory
tract. Manifestations include symptoms of the common cold,
pharyngitis, pharyngoconjunctival fever, tonsillitis, otitis media,
keratoconjunctivitis, often associated with fever. Life-threatening
disseminated infection, severe pneumonia, meningitis, and encephalitis
occasionally occur, especially among young infants and
immunocompromised hosts. Adenoviruses are infrequent causes of
acute hemorrhagic conjunctivitis, a pertussis-like syndrome, croup,
bronchiolitis, hemorrhagic cystitis, and genitourinary tract disease.
In children, the best described syndrome attributed to adenoviruses is
the so-called pharyngoconjunctival fever. This disease occurs in small
outbreaks and seen by physicians at children’s summer camps. It is
characterized by conjunctivitis, pharyngitis, rhinitis, cervical adenitis,
and temperatures to 380C. The onset is acute, and the fever and other
symptoms last 3-5 days. Bulbar and palpebral conjunctivitis may be the
only finding, and the palpebral conjunctivae usually have a granular
appearance.
A few adenovirus serotypes, types 40 and 41, have been associated with
gastroenteritis, and are responsible for about 4% of serious diarrhea in
infants and children.
The predominant cause of exudative tonsillitis in infants and toddlers is
of adenoviral etiology.
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3.
What is known about the pathogenesis of adenoviral infections?
The oropharyngeal and nasopharyngeal mucous membranes are the
tissues primarily affected early in acute infection.
Adenoviruses appear to be capable of at least three types of interaction
with cells.
1) The first is a lytic infection in which the virus goes through an entire
replicative cycle. Lytic infection occurs in human epithelial cells and
results in cell death and in the production of 10,000 – 1 million progeny
viruses per cell, of which 1-5 percent are infectious.
2) The second interaction is a latent or chronic infection. This usually
involves lymphoid cells. During latent infection, only small numbers of
viruses may be released, and cell death may be outstripped by cell
multiplication, thereby resulting in inapparent infection. The
mechanisms are not clearly established.
3) The third significant virus – cell interaction occurring with
adenoviruses is that of oncogenic transformation. In this situation, only
the early steps in virus replication occur. The viral DNA is apparently
integrated into and replicated with the cell’s DNA, but no infectious
virions are produced. In all three types of infection, virus-specific
proteins (T antigens) are synthesized. These antigens give evidence of
adenoviral presence even in the absence of infectious virus. The T
antigens are detected either by complement fixation or by
immunofluorescence assays using serum from hamsters bearing
tumors induced by adenovirus.
4.
What type of isolation should the patient be in while in the hospital?
For young children with respiratory tract infection, contact and droplets
precautions are indicated for the duration of hospitalization. For
patients with conjunctivitis, contact precautions in addition to standard
precautions are recommended. For diapered and incontinent children
with adenoviral gatroenteritis, contact precautions in addition to
standard precautions are indicated for the duration of the illness.
5.
How is the viral infection detected?
Detection of adenovirus infection by culture or antigen is the preferred
diagnostic method.
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Adenoviruses associated with respiratory tract disease can be isolated
from pharyngeal secretions, eye swabs, and feces by inoculation of
specimens into a variety of cell cultures. A pharyngeal isolate is more
suggestive of recent infection than is a fecal isolate, which may indicate
either prolonged carriage or recent infection.
Adenovirus antigens can be detected in body fluids of infected persons
by immunoassay techniques, which are especially useful for diagnosis
of diarrheal disease, because enteric adenovirus types 40 and 41
usually cannot be isolated in standard cell cultures. Enteric
adenoviruses also can be identified by electron microscopy of stool
specimens. Multiple methods to detect group-reactive hexon antigens
in body secretions and tissue have been developed. Also, detection of
viral DNA can be accomplished with genomic probes, synthetic
oligonucleotide probes, or gene amplification by polymerase chain
reaction. Serodiagnosis is based on detecting a 4-fold or greater rise in
antibodies to a common adenovirus antigen (eg, hexon). Serodiagnosis
is used primarily for epidemiologic studies.
6.
Describe the measures for prevention of the spread of adenoviral infection.
Adequate chlorination of swimming pools is recommended to prevent
pharyngoconjunctival fever. Epidemic keratoconjunctivitis associated
with ophthalmologic practice can be difficult to control and requires use
of single-dose medication dispensing and strict attention to hand
washing and instrument sterilization procedures. Effective disinfection
can be accomplished by immersion of contaminated equiment in a 1%
solution of sodium hypochlorite for 10 minutes or by steam autoclaving.
Health care personnel with known or suspected adenoviral
conjunctivitis should avoid direct patient contact for 14 days after the
onset of disease in their second eye. Because adenoviruses are
particularly difficult to eliminate from skin, fomites, and environmental
surfaces, assiduous adherence to hand washing and use of disposable
gloves when caring for infected patients are recommended.
Children who participate in group child care, particularly children from 6
months through 2 years of age, are at increased risk of adenoviral
respiratory tract infections and gastroenteritis. Measures for preventing
spread of adenovirus infection in this setting have not been determined,
but frequent hand-washing is recommended.
Respiratory Tract Infection Faculty Copy – Page 20
CASE 1
Slide 1 Mild RSV pneumonia
There are mild peribronchial infiltrates and the lungs are hyperinflated because of air
trapping (air gets in but can’t get out ) because of mucous necrotic debris in the
airways.
Slide 2 Lateral view of Slide 1
Shows that the lungs are hyperinflated because diaphragms are flattened.
Slides 3 - 5
Increasingly progressive RSV pneumonia in infants with congenital heart disease.
There are patchy infiltrates and hyperinflation from air trapping. The presence of
infiltrates is common in severe RSV pneumonia and does not imply the presence of
a secondary bacterial pneumonia.
Respiratory Tract Infection Faculty Copy – Page 21
OPTIONAL ARTICLES FOR RESPIRATORY VIRUSES CASE STUDIES II
Respiratory Tract Infection Faculty Copy – Page 22
1.
RSV Bronchiolitis (1997)-American Family Physician, Vol. 55:1139-1146.
2.
Respiratory Syncytial Virus Infection: Indications for the use of Palivizumab
and Update on the use of RSV-IG IV. (1998) Pediatrics 102:1211-1216.
3.
Croup: An 11 year Study in a Pediatric Practice. (1983) Pediatrics, Vol
71:871-876.
4.
A comparison of Nebulized Budesonide, Intramuscular Dexamethasone and
Placebo for Moderately Severe Croup. (1998) NEJM 339:498-503.
5.
Epstein-Barr Virus Infection (2000). NEJM 343:481-492.
6.
Inhaled Zanamivir for the Prevention of Influenza in Families (2000), NEJM
343:1282-1289.
7.
Drug Therapy: Prevention and treatment of Influenza (2000). NEJM
343:1778-1787.
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