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Viral Diseases
Victor Politi, MD,FACP
Medical Director, SVCMC School of
Allied Health Professions, Physician
Assistant Program
Introduction
• In 1898, Friedrich Loeffler and Paul Frosch
found evidence that the cause of foot-and-mouth
disease in livestock was an infectious particle
smaller than any bacteria.
Friedrich
Loeffler
• This was the first clue to the nature of viruses,
genetic entities that lie somewhere in the grey
area between living and non-living states.
Introduction
• Viruses depend on the host cells that they
infect to reproduce.
• When found outside of host cells, viruses
exist as a protein coat or capsid,
sometimes enclosed within a membrane.
• The capsid encloses either DNA or RNA
which codes for the virus elements.
Introduction
• When it comes into contact with a host
cell, a virus can insert its genetic material
into its host, literally taking over the host's
functions.
• An infected cell produces more viral
protein and genetic material instead of its
usual products.
Introduction
• Some viruses may remain dormant inside
host cells for long periods, causing no
obvious change in their host cells (a stage
known as the lysogenic phase)
Lysogenic cycle
In the lysogenic cycle,
the virus reproduces
by first injecting its
genetic material,
indicated by the red
line, into the host
cell's genetic instructions.
Lytic Phase
• But when a dormant virus is stimulated, it
enters the lytic phase: new viruses are
formed, self-assemble, and burst out of
the host cell, killing the cell and going on
to infect other cells.
Lytic phase/cycle
In the lytic cycle,
The virus reproduces
itself using the host
cell's chemical machinery.
The red spiral lines in
the drawing indicate
the virus's genetic material.
The orange portion is the
outer shell that protects it.
Transduction
• Viruses also carry out natural "genetic
engineering": a virus may incorporate some
genetic material from its host as it is replicating,
and transfer this genetic information to a new
host, even to a host unrelated to the previous
host.
• This is known as transduction, and in some
cases it may serve as a means of evolutionary
change - although it is not clear how important
an evolutionary mechanism transduction actually
is.
• Viruses cause a number of diseases in
eukaryotes.
• In humans, smallpox, the common cold,
chickenpox, influenza, shingles, herpes,
polio, rabies, Ebola, hanta fever, and AIDS
are examples of viral diseases.
• Even some types of cancer -- though
definitely not all -- have been linked to
viruses.
• Virus particles are about one-millionth of
an inch (17 to 300 nanometers) long.
• Viruses are about a thousand times
smaller than bacteria, and bacteria are
much smaller than most human cells.
• Viruses are so small that most cannot be
seen with a light microscope, but must be
observed with an electron microscope.
Relative size of viruses and
bacteria
Relative size of DNA viruses
Relative size of positive strand
RNA viruses
Relative size of negative strand
RNA viruses
• The internationally agreed system of virus
classification is based on the
structure/composition of the virus particle
(virion)
• In some cases, the mode of replication is
also important in classification.
• Viruses are classified into various families
on this basis.
• A virus particle, or virion, consists of the
following:
– Nucleic acid - either DNA or RNA, either singlestranded or double-stranded
– Coat of protein - Surrounds the DNA or RNA to
protect it
– Lipid membrane - Surrounds the protein coat (found
only in some viruses, including influenza; these types
of viruses are called enveloped viruses as opposed
to naked viruses)
• Viruses can exist for a long time outside the
body.
• The way that viruses spread is specific to the
type of virus. They can be spread through the
following means:
– Carrier organisms – mosquitoes,ticks, fleas
– The air
– Direct transfer of body fluids from one person to
another - saliva, sweat, nasal mucus, blood, semen,
vaginal secretions
– Surfaces on which body fluids have dried
Papillomaviruses
• Papilloma viruses are wart-causing viruses that
cause human neoplasms
• Warts are usually benign but can convert to
malignant carcinomas.
• This occurs in patients with epidermodysplasia
verruciformis.
• Papilloma viruses are also found associated with
human penile, uterine and cervical carcinomas
and are very likely to be their cause.
Epidermodysplasia verruciformis
• This widespread, markedly pruritic,
erythematous eruption was eventually
found to be caused by human
papillomavirus infection.
Papillomaviruses
• There are 51 types of papilloma viruses
• Not all are associated with cancers;
however, papillomas may cause 16% of
female cancers worldwide and 10% of all
cancers.
Papilloma virus
Papillomaviruses
• Vulvar, penile and cervical cancers are
associated with type 16 and type 18
papilloma viruses.
• The most common genital human
papilloma viruses (HPV) are types 6 and
11.
Human polyoma viruses
• This virus causes progressive multifocal
leukoencephalopathy ,a disease
associated with immunosuppression.
• In 1979, the rate of occurrence of this
disease was 1.5 per 10 million population.
• It has become much more common
because of AIDS and is seen in 5% of
AIDS patients.
Herpes Viruses
• Herpes viruses are a leading cause of
human viral disease, second only to
influenza and cold viruses.
• They are capable of causing overt disease
or remaining silent for many years only to
be reactivated, for example as shingles.
Herpes Viruses
• The name herpes comes from the Latin
herpes which, in turn, comes from the
Greek word herpein which means to
creep.
• This reflects the creeping or spreading
nature of the skin lesions caused by many
herpes virus types.
Human Herpes viruses
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Herpes simplex virus (HSV) type 1
HSV type 2
Varicella zoster virus (type 3)
Epstein-barr (EB) infectious mononucleosis virus
(type 4)
Cytomegalovirus –CMV type 5
HHV-6 (causative agent of roseola)
HHV-7
HHV-8- linked with Kaposi sarcoma
Human Herpes viruses
• Once a patient has become infected by
herpes virus, the infection remains for life.
• The initial infection may be followed by
latency with subsequent reactivation.
Human Herpes viruses
• Herpes viruses infect most of the human
population and persons living past middle
age usually have antibodies to most of the
above herpes viruses with the exception of
HHV-8.
Herpes viruses 1 & 2
• Herpes simplex 1 and 2 are frequently benign
but can also cause severe disease.
• In each case, the initial lesion looks the same.
– A clear vesicle containing infectious virus with a base
of red (erythomatous) lesion at the base of the
vesicle.
– This if often referred to as a 'dewdrop on a rose petal'.
– From this pus-containing (pustular), encrusted lesions
and ulcers may develop.
Herpes viruses 1 & 2
• Affect primarily the oral and genital areas
• Disease is typically a manifestation of
reactivation
– Triggers for clinical reactivation are not well
understood
Herpes Viruses 1&2
• Herpes simplex type 1 (HSV-1)
– Largely involves mouth/oral cavity (herpes
labialis)
– Can cause urogenital infections
• HSV-2
– Most common cause of genital ulcers in
developing world
HSV-1
• Primary infection may be asymptomatic
• Vesicles form moist ulcers after several
days
– if untreated epithelialize over 1-2 weeks
• Recurrences
– Tend to be labial
– Heal faster
– Induced by stress, fever, infection, sunlight
HSV-2
• Genital herpes is usually the result of HSV-2 with
about 10% of cases being the result of HSV-1.
• Primary infection is often asymptomatic but
many painful lesions can develop on the glans
or shaft of the penis in men and on the vulva,
vagina, cervix and perianal region of women
Largely involve genital tract
Hsv-2
• Typical lesions
– Multiple, painful, small, grouped and
vesicular
HSV- Diagnosis
• Usually made on clinical grounds
• Viral cultures of vesicular fluid
• Direct fluorescent antibody staining of scraped
lesions
• In serum – can be identified using PCR
• Cells may be obtained from the base of the
lesion (called a Tzank smear) and
histochemistry performed
• presence of intranuclear inclusions and
multinucleated giant cells supportive of dx of
herpes
HSV-Clinical Findings
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Ocular dx (keratitis, blepharitis, keratoconjunctivitis)
Neonatal & congenital infection
Encephalitis/recurrent meningitis
Disseminated infection
Bell’s Palsy
Esophagitis
Erythema Multiforme
Herpes keratitis
• This is an infection of the eye and is
primarily caused by HSV-1.
• It can be recurrent and may lead to
blindness.
• It is a leading cause of corneal blindness
in the United States.
Herpes whitlow
This disease of persons
who come in manual
contact with herpes-infected
body secretions can be
cause by either type of
HSV and enters the
body via small wounds
on the hands or wrists.
It can also be caused by transfer of
HSV-2 from genitals to the hands
HSV encephalitis
• This is usually the result of an HSV-1 infection
and is the most common sporadic viral
encephalitis.
• HSV encephalitis is a febrile disease and may
result in damage to one of the temporal lobes.
• As a result there is blood in the spinal fluid and
the patient experiences neurological symptoms
such as seizures.
• The disease can be fatal but in the US there are
fewer than 1000 cases per year.
HSV- Treatment/Prevention
• Urogenital, encephalitic or disseminated
disease
– acyclovir & related compounds
• Keratitis
– trifluridine
• Resistant strains in immunocompromised
– foscarnet
Prevention
• Recurrent mucocutaneous disease is most
effectively treated with acyclovir
• Recurrent genital disease also requires
barrier precautions during sexual activity
• Asymptomatic transmission occurs –
especially with HSV-2
Varicella & Herpes Zoster
Chicken pox or shingles (its reactivation)
• Chicken Pox
– Highly contagious
– Generally dx of childhood
– Spread by inhalation of
infected droplets or contact
with lesions after 10-20
days
– Fever/malaise mild in
children
– Pruritic rash evolves
centrifugally – beginning on
face/scalp/trunk – lesser
degree on extremities
• Shingles
– After primary infection virus
remains dormant in
nervous tissue
– Pain often severe, may
precede rash
– Lesions follow any nerve
root distribution – typically
thoracic & lumbar
– Ramsay Hunt Syndrome –
geniculate ganglion
involvement
• Typical isolated rash in shingles
• In severe cases of shingles, the lesions
coalesce, forming a disfiguring carpet of
scabs and sometimes the rash leaves
permanent scars
Varicella & Herpes Zoster
Chicken pox or shingles (its reactivation)
• Varicella Complications –
– Interstitial pneumonia
• more common in adults than children
– Hepatitis
– Reye’s syndrome
• Usually in childhood/associated with aspirin use
– Congenital malformation
• congenital varicella syndrome which leads to scarring of the
skin of the limbs, damage to the lens, retina and brain and
microphthalmia
– Secondary bacterial infection
• Group A beta-hemolytic streptococci common
Varicella & Herpes Zoster
Chicken pox or shingles (its reactivation)
• Herpes Zoster
– Postherpetic neuralgia
• Occurs in 60-70% of patients > age 60
– Encephalitis, skin lesions beyond the
dermatome, and visceral lesions
• Seen in immunocompromised & HIV patients
Epstein- Barr Virus
Epstein-Barr virus is the causative agent
of Burkitt's lymphoma in Africa, nasal
pharyngeal carcinoma in the orient and
infectious mononucleosis in the west.
EBV
• Why this virus causes a benign disease in
some populations but malignant disease in
others is unknown.
Burkitt's Lymphoma caused by Epstein-Barr Virus
Infectious mononucleosis
• The primary infection is often asymptomatic.
• Some patients develop infectious mononucleosis after 12 months of infection.
• The disease is characterized by malaise,
lymphadenopathy, tonsillitis, enlarged spleen and liver
and fever.
• The fever may persist for more than a week.
• There may also be a rash.
• The severity of disease often depends on age (with
younger patients resolving the disease more quickly) and
resolution usually occurs in 1 to 4 weeks.
Infectious mononucleosis
Complications
• Complications include:
– neurological disorders such as meningitis,
encephalitis, myelitis and Guillain-Barrè
syndrome
– Secondary infections,
– autoimmune hemolytic anemia,
– thrombocytopenia
– agranulocytosis,
– aplastic anemia
Infectious mononucleosis
• A large proportion of the population (9095%) is infected with Epstein-Barr virus
and these people, although usually
asymptomatic, will shed the virus from
time to time throughout life.
• The virus is spread by close contact
(kissing disease).
Infectious mononucleosis
• Up to 80% of students entering college in
the US are seropositive for the virus and
many of those that are negative will
become positive while at college.
• The virus can also be spread by blood
transfusion.
• Tongue and palate of patient with
infectious mononucleosis.
Infectious mononucleosis Dx
• In infectious mononucleosis, blood smears
show the atypical lymphocytes (Downey
cells).
• There are also serological tests available.
• Heterophile antibodies are produced by
the proliferating B cells and these include
an IgM that interacts with Paul-Bunnell
antigen on sheep red blood cells.
Infectious mononucleosis- Tx
• Unlike herpes simplex virus, there are no
drugs available to treat Epstein-Barr virus.
• A vaccine is being developed.
Major Vaccine –Preventable Viral
Infections
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Measles
Mumps
Poliomyelitis
Rubella
Measles
• Before the advent of the current measles
vaccine, there were about 500,000 cases
of measles in the United States per year;
almost everyone got the measles.
• Infection is via an aerosol route and the
virus is very contagious.
Measles
• Uncomplicated disease is characterized by the
following:
– Fever of 101 degrees Fahrenheit or above
– Respiratory tract symptoms: running nose (coryza)
and cough
– Conjunctivitis
– Koplik's spots on mucosal membranes - small (1 3mm), irregular, bright red spots, with bluish-white
speck at center. The patient may get an enormous
number and red areas may become confluent
– Maculopapular rash which extends from face to the
extremities.
Measles
• Koplik’s spots on palate due to preeruptive measles on day 3 of the illness
Measles
• classic day-4 rash with measles.
Measles Complications
• CNS
– Encephalitis
– Subacute sclerosing panencephalitis
– Subacute measles encephalitis
• Respiratory Tract
– Bronchopneumonia
– bronchiolitis
• Secondary bacterial infection
• Gastroenteritis
Measles Prevention/Tx
• Prevention
– Vaccination
• Treatment
– Isolation one week following onset of rash
– Symptomatic
– Vitamin A 200,000 units/d orally reduces
pediatric morbidity rates (maintenance of GI
and respiratory epithelial mucosa, immune
enhancement)
Mumps
• Mumps is usually defined as acute
unilateral or bilateral parotid gland swelling
that lasts for more than two days with no
other apparent cause.
• Mumps is very contagious and is probably
usually acquired from respiratory
secretions and saliva via aerosols or
fomites.
Mumps
• The virus is secreted in urine and so urine
is a possible source of infection.
• It is found equally in males and females.
Mumps
• Before 1967, most mumps patients were
under 10 years of age but since the advent
of the attenuated vaccine, the remaining
cases occur in older people with almost
half being 15 years of age or older.
Mumps
• Inflammation, parotitis, in a child with
mumps.
• Virus is shed in saliva from 3 days before
to 6 days after symptoms
Pathogenesis of mumps
• Virus infects upper/lower respiratory tract
leading to local replication.
• The virus spreads to lymphoid tissue
which, in turn, leads to viremia.
• The virus thus spreads to a variety of
sites, including salivary, other glands and
other body sites (including the meninges).
Pathogenesis of mumps
Symptoms of Mumps
• Parotitis
• Fever and malaise
• Deafness
– was a leading cause of acquired deafness before the
advent of mumps vaccines but hearing loss is rare
(one in every 20,000 mumps cases).
• Orchioitis
– especially severe in adolescent and adult males and
occurs in about 50% of cases
Mumps Complications
• Meningitis
• Pancreatitis
– Leading cause in children
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Oophoritis
Thyroiditis
Neuritis
Hepatitis
Myocarditis
Thrombocytopenia
Migratory arthralgias
nephritis
Mumps Prevention/Tx
• Prevention
– Vaccination
• Treatment
– Symptomatic
– Isolation
Rubella
• Rubella (which means "little red" and is
also known as German measles) was
originally though to be a variant of
measles.
• It is a mild disease in children and adults,
but can cause devastating problems if it
infects the fetus, especially if infection is in
the first few weeks of pregnancy.
Rubella
• Rubella virus is spread via an aerosol
route and occurs throughout the world.
• The initial site of infection is the upper
respiratory tract.
• The virus replicates locally (in the
epithelium, lymph nodes) leading to
viremia and spread to other tissues.
• As a result the disease symptoms
develop.
Rubella
• Rash (if it occurs) starts after an
incubation period of approximately 2
weeks (12 to 23 days) from the initial
infection.
• There is usually no prodrome in young
children but in older children and adults
disease results in low grade fever, rash,
sore throat and lymphadenopathy.
Rubella
• Complications are extremely rarely (1 in
6000 cases).
– Rubella encephalopathy may occur about 6
days after rash. It usually lasts only a few
days and most patients recover (no
sequelae). If death occurs, it is within few
days of onset of symptoms.
• Other rare complications include orchitis,
neuritis and panencephalitis.
Rubella
• The risk to a fetus is highest in the first few
weeks of pregnancy and then declines in
terms of both frequency and severity.
Rubella
• Congenital rubella with hemorrhagic
lesions in the skin.
Rubella
• The sequelae of congenital rubella syndrome
are:
– Hearing loss. This is the most common sequella of
congenital rubella infection especially when the latter
occurs after four months of pregnancy.
– Congenital heart defects
– Neurologic problems (psychomotor retardation,
mental retardation, microcephaly)
– Ophthalmic problems intrauterine growth retardation
– Thrombocytopenia purpura
– Hepatomegaly
– Splenomegaly
Rubella
• Baby born with rubella:
– Thickening of the lens of the eye that causes
blindness (cataracts)
Rubella Treatment/Prevention
• Treatment
– There is no specific treatment.
– Supportive care should be used
• Vaccination
– Childhood Immunization
– It is important that women are vaccinated
prior to their first pregnancy.
•
ENTEROVIRUSES
• Enteroviruses are spread via the fecal-oral
route.
• The ingested viruses infect cells of the
oro-pharyngeal mucosa and lymphoid
tissue (tonsils) where they are replicated
and shed into the alimentary tract.
• From here they may pass further down the
gastrointestinal tract.
ENTEROVIRUSES
• Most patients infected with an enterovirus
remain asymptomatic but in small children
benign fevers caused by unidentified
enteroviruses are relatively common (nonspecific febrile illness).
• Many outbreaks of febrile illness
accompanied by rashes are also caused
by enteroviruses
Poliovirus
• Poliovirus caused about 21, 000 cases of
paralytic poliomyelitis in the United States
each year in the 1940's - 50's prior to the
introduction of the Salk (inactivated) and
Sabin (attenuated) vaccines.
• Infection by polio virus is, in most cases,
asymptomatic.
Abortive poliomyelitis
(minor illness)
• The first symptomatic result of polio
infection is febrile disease and occurs in
the first week of infection.
• The patient may exhibit a general malaise
which may be accompanied by vomiting, a
headache and sore throat.
• This is abortive poliomyelitis and occurs in
about 5% of infected individuals
Non-paralytic poliomyelitis
• Three or four days later a stiff neck and
vomiting, as a result of muscle spasms,
may occur in about 2% of patients.
• This is similar to aseptic meningitis. The
virus has now progressed to the brain and
infected the meninges.
Paralytic polio
• About 4 days after the end of the first minor
symptoms, the virus has spread from the blood
to the anterior horn cells of the spinal cord and
to the motor cortex of the brain.
• The degree of paralysis depends on the which
neurons are affected and the amount of damage
that they sustain.
• The disease is more pronounced in very young
and very old patients.
Paralytic polio
• In spinal paralysis one or more limbs may
be affected or complete flaccid paralysis
may occur
• .
Paralytic polio
• In bulbar paralysis cranial nerves and the
respiratory center in the medulla are
affected leading to paralysis of neck and
respiratory muscles.
• There is no sensory loss associated with
the paralysis.
Paralytic polio
• The degree of paralysis may increase over
a period of a few days and may remain for
life or there may be complete recovery
over period of 6 months to a few years
Paralytic polio
• In bulbar poliomyelitis, death may also
ensue in about three quarters of patients,
especially when the respiratory center is
involved.
• Patients were able to survive for a while
using an iron lung to aid
respiration.
• The morality rate of
paralytic polio is 2-3%
Post-polio syndrome
• This afflicts victims of an earlier polio virus
infection but the virus is no longer present.
• It may occur many years after the infection
and involves further loss of function in
affected muscles perhaps as a result of
further neuron loss.
COXSACKIE VIRUSES
• There are many infections caused by
Coxsackie viruses, most of which are
never diagnosed precisely.
COXSACKIE VIRUSES
• Coxsackie type A
– usually is associated with surface rashes
(exanthems) while
• Coxsackie type B
– typically causes internal symptoms
(pleurodynia, myocarditis)
• but both can also cause paralytic disease
or mild respiratory tract infection.
COXSACKIE VIRUSES
• Enteroviruses are the major cause of viral
meningitis.
• Both Coxsackie virus A and B can cause
aseptic meningitis which is so-called
because it is not of bacterial origin.
COXSACKIE VIRUSES
• Viral meningitis typically involves a headache,
stiff neck, fever and general malaise.
• Lymphocyte pleocytosis of the cerebrospinal
fluid is often observed.
• Most patients recover from the disease unless
encephalitis occurs although there may be mild
neurological problems.
• The disease is most prevalent in the summer
and fall.
COXSACKIE VIRUSES
Herpangina
• Coxsackie virus A can cause a fever with painful
ulcers on the palate and tongue leading to
problems swallowing and vomiting.
• Treatment of the symptoms is all that is required
as the disease subsides in a few days.
• Despite its name, the disease has nothing to do
with herpes or the chest pain known as angina.
COXSACKIE VIRUSES
Hand, foot and mouth disease
• This is an exanthem caused by Coxsackie
type A16.
• Symptoms include fever and blisters on
the hands, palate and feet.
• It subsides in a few days.
• Many other exanthems may be caused by
Coxsackie virus or Echoviruses.
COXSACKIE VIRUSES
Hand, foot and mouth disease
COXSACKIE VIRUSES
Hand, foot and mouth disease
• Coxsackie virus A and B (and also
Echoviruses) can cause myocarditis in
neonates and young children.
• Fever, chest pains, arrhythmia and even
cardiac failure can result.
• Mortality rates are high.
• In young adults, an acute benign
pericarditis may also be cause by
Coxsackie viruses
COXSACKIE VIRUSES
Bornholm disease (Pleurodynia, the Devil's Grippe)
• Usually caused by Coxsackie A, these upper
respiratory tract infections can result in fever
and sudden sharp pains in the intercostal
muscles on one side of the chest.
• There may also be pain in the abdomen and
vomiting.
• The incubation period is 2 to 4 days and
symptoms subside after a few days although
relapses can occur.
Other enterovirus diseases
• Non-specific febrile disease can be
caused by several enteroviruses.
• These infections are among the most
common reasons that small children are
admitted to hospital in order to rule out a
bacterial cause.
Other enterovirus diseases
• Admissions peak in the late summer/fall.
• Disease normally resolves but can be of
consequence in the very young.
• Coxsackie B virus may result in severe
neonatal disease including hepatitis,
meningitis, myocarditis and adreno-cortical
problems.
Other enterovirus diseases
• Infections often spread through nurseries
and are difficult to stop because of the
resistance of the virus to disinfecting
agents.
PARAINFLUENZA, RESPIRATORY
SYNCYTIAL AND ADENO VIRUSES
PARAINFLUENZA VIRUS
• Parainfluenza viruses are viral pathogens
causing upper and lower respiratory
infections in adults and children.
• Parainfluenza viruses -relatively large
viruses of about 150-300 nm in diameter.
PARAINFLUENZA VIRUS
• Infections occur as epidemics as well as
sporadically.
• Parainfluenza viruses are sensitive to detergents
and heat but can remain viable on surfaces for
up to 10 hours.
• Transmission occurs via the following routes:
– Large droplets - person to person through close
contact
– Aerosols of respiratory secretions
– Fomites (virus survives on surfaces)
PARAINFLUENZA VIRUS
• Incubation period is 2 to 6 days.
• Most infections are asymptomatic,
especially in older children and adults.
• Primary infections and re-infections occur.
• Most persons have had primary infections
before the age of 5 yrs.
PARAINFLUENZA VIRUS
• Reinfections are clinically less severe,
most commonly involve the upper
respiratory tract and occur throughout life.
• Fever and a spectrum of respiratory
infections are caused by PIVs
– Rhinorrhea/rhinitis, pharyngitis, cough, croup
(laryngotracheobronchitis), bronchiolitis, and
pneumonia
PARAINFLUENZA VIRUS
Antigen detection
• Radio-immunoasay, enzyme immunoassay,
fluoro-immunoassay, and immunofluoresence
methods are used for antigen detection.
• Nasopharyngeal secretions are collected, from
swabs or washings and transported in viral
transport medium and on ice.
• Shell vial assay is useful in detecting growth in
4-7 days. Hemadsorption can be noted before
cytopathic effects. Immunofluoresence is
confirmatory.
PARAINFLUENZA VIRUS
• There is no specific treatment.
• Supportive treatment for croup includes
humidification of air and racemic
epinephrine.
• Corticosteroids may be used in moderate
to severe cases.
PARAINFLUENZA VIRUS
• Immunity following infection is short lived.
• The role of antibody is not clear since
reinfection has been seen even with high
levels of antibody.
• Cell-mediated Immunity (CMI) is probably
more important for limiting infection.
RESPIRATORY SYNCYTIAL
VIRUS
• These viruses survive on surfaces for up
to 6 hours, on gloves for less than 2
hours.
• They rapidly lose viability with freeze-thaw
cycles, in acidic conditions and with
disinfectants.
RSV
• RSV has a worldwide distribution and
most children have had an RSV infection
by age 4 years
• Out breaks are seasonal occurring from
late fall through spring (November to May)
• The virus is transmitted via large droplets,
through fomites and via hands
RSV -Epidemiology
• The virus enters through the eyes and
nose
• Viral shedding continues for less than 1 to
3 weeks but longer in immunocompromised hosts
• RSV is the most frequent cause of
bronchiolitis but is an infrequent cause of
croup
RSV-Clinical Features
• Incubation Period: 4 - 6 days (range: 2 - 8
days)
• Upper respiratory infection (‘bad cold’) in
older children and adults:
• Clinical features: fever, rhinitis, pharyngitis
RSV- Clinical Features
• Lower respiratory infection- Bronchiolitis
and/or pneumonia may occur after the
upper respiratory infection:
• Clinical features: cough, tachypnea,
respiratory distress, hypoxemia, cyanosis.
• Cough can persist for 3 weeks.
RSV- Clinical Features
• In young infants - apnea, lethargy,
irritability, poor feeding.
• Radiological features: atelectasis,
streaking, hyperinflation.
• Severe infections occur in pre-term infants
(especially less than 35 weeks gestation
and those with chronic lung disease),
children with cyanotic congenital heart
disease, and immuno-compromised hosts.
RSV-Dx/Tx
• Nasal washings, nasal aspirates or swabs
• Treatment is usually supportive –
– fluids, oxygen, humidification of air,
respiratory support, bronchodilators
ADENOVIRUS
• Almost half of adenoviral infections are
subclinical
• Most infections are self-limited and induce
type-specific immunity
• Incubation period is 2-14 days; for
gastroenteritis usually 3-10 days
Adenovirus Symptoms
• Eye
– Epidemic Keratoconjunctivitis (EKC), acute
follicular conjunctivitis, pharyngoconjunctival
fever
• Respiratory system
– rhinitis, pharyngitis (with or without fever),
tonsillitis, bronchitis, pharyngoconjunctival
fever, acute respiratory disease (LRI),
pertussis-like syndrome, pneumoniasometimes with sequelae
Adenovirus Symptoms
• Genitourinary
– Acute hemorrhagic cystitis, orchitis, nephritis,
oculogenital syndrome
• Gastrointestinal
– Gastroenteritis, mesenteric adenitis,
intussusception, hepatitis, appendicitis.
Diarrhea tends to last longer than with other
viral gastroenteritides
Adenovirus Complications
• Rare results of adenovirus infections
include– Meningitis, encephalitis, arthritis, skin rash,
myocarditis, pericarditis, hepatitis.
– Fatal disease may occur in
immunocompromised patients, as a result of a
new infection or reactivation of latent virus
Adenovirus - Epidemiology
• Endemic, epidemic and sporadic infections
occur.
• Outbreaks have been noted in military
recruits, swimming pool users, residential
institutions, hospitals, day care centers
etc.
• Transmission: Droplets, fecal-oral route
(direct and through poorly chlorinated
water), fomites
Adenovirus - Epidemiology
• Infections are most communicable in the
first few days of illness, however infective
period continues since clinical infection
may be followed by intermittent and
prolonged rectal shedding
• Secondary attack rate within families: up
to 50%;
Adenovirus
• Adenovrius outbreaks:
– Respiratory disease mainly occurs in late
winter through early summer.
– Pharyngoconjunctival and EKC infections
occur in the summer months
– However GI disease does not seem to be
seasonal
Influenza
• True influenza is an acute infectious
disease caused by a member of the
orthomyxovirus family
• The term 'flu' is often used for any febrile
respiratory illness with systemic symptoms
that may be caused be a myriad of
bacterial or viral agents as well as
influenza.
Influenza
• Influenza outbreaks usually occur in the
winter in temperate climates.
• In the United States, the 'flu season
usually starts in October or November and
is at its height from December to March
Influenza
• Major outbreaks of influenza are
associated with influenza virus type A or B.
• Infection with type B influenza is usually
milder than type A.
• Type C virus is associated with minor
symptoms.
Influenza
• The virus is spread person to person via
small particle aerosols (less than 10µm)
which can get into respiratory tract.
• The incubation period is short, about 18 to
72 hours.
Influenza
• Virus concentration in nasal and tracheal
secretions remains high for 24 to 48 hours
after symptoms start and may last longer
in children.
• Titers are usually high and so there are
enough infectious particles in a small
droplet to start a new infection.
Influenza
• Influenza virus infects the epithelial cells of
the respiratory tract.
• The disease is usually most severe in very
young children and the elderly.
Influenza & Children
• Children may have no antibodies and the
small diameter of components of the
respiratory tract in the very young mean
that inflammation and swelling can lead to
blockage of parts of respiratory tract, sinus
system or Eustachian tubes.
Influenza & the Elderly
• In the elderly, influenza is often severe
because they often have an underlying
decreased effectiveness of the immune
system and/or chronic obstructive
pulmonary disease or chronic cardiac
disease.
Influenza – Statistics
• CDC surveys show that each year about
114,000 people in the U.S. are
hospitalized and about 36,000 people die
because of the flu.
Influenza – Statistics
• Flu and pneumonia together constitute the
sixth leading cause of deaths in the United
States.
– Most flu fatalities are 65 years and older.
– Children younger than 2 years old are as
likely as those over 65 to have to be
hospitalized because of the flu.
Influenza -Symptoms
• Uncomplicated influenza
– Fever
– Myalgias, headache
– Ocular symptoms - photophobia, tears, ache
– Dry cough, nasal discharge
Influenza - Complications
• Pulmonary complications:
– Croup in young children - symptoms include
cough (like a barking seal), difficulty
breathing, stridor (crowing sound in
inspiration)
– Primary influenza virus pneumonia
– Secondary bacterial infection:
• Often involves Streptococcus pneumoniae,
Staphylococcus aureus, Hemophilus influenzae
Influenza - Complications
• Complications often occur in patients with
underlying chronic obstructive pulmonary
or heart disease.
• The underlying problems may not have
been recognized prior to the influenza
infection.
Influenza - complications
• Non-pulmonary complications:
– Myositis (rare, more likely to be seen in
children after type B infection)
– Cardiac complications
– Encephalopathy
– Reye’s Syndrome
– Guillain Barre Syndrome
Influenza - Complications
• The major causes of influenza-associated
death are bacterial pneumonia and cardiac
failure. Ninety per cent of deaths are in
people over 65 years of age.
Influenza - Dx
• Firm diagnosis is by means of virus
isolation and serology. The virus can be
isolated from the nose or a throat swab.
Influenza Prevention
• A new vaccine is formulated annually with
the types and strains of influenza
predicted to be the major problems for that
year (predictions are based on worldwide
monitoring of influenza).
• The vaccine is multivalent and the current
one is to two strains of influenza A and one
of influenza B.
Influenza - Tx
• The best treatments are rest, liquids, antifebrile agents (not aspirin in the young or
adolescent, since Reye's disease is a
potential problem).
• Be aware of and treat complications
appropriately.
ROTAVIRUSES
• Rotavirus is stable in the environment and
is relatively resistant to handwashing
agents.
• Is susceptible to disinfection with 95%
ethanol, ‘Lysol’, formalin and in
environments with pH<2.
ROTAVIRUSES
• Distribution –
– Worldwide, causing 600,000-850,000 deaths
per year (figure 3).
• Seroprevalence studies show that
antibody is present in most infants by age
3 years.
• In the U.S., there are 20 - 40 deaths per
year with 50,000 hospitalizations per year
• Dehydration=1-2.5%
ROTAVIRUSES
• In the U.S.A., rotavirus infections occur in
the winter months (November through
May).
• Incubation period - thought to be <4 days
• Contagious Period - Before onset of
diarrhea to a few days after end of
diarrhea
ROTAVIRUSES
• Age - Rotaviruses infect children at a
young age.
• Older infants and young children (4
months - 2 years) tend to be more
symptomatic with diarrhea.
• Young infants may be protected due to
trans-placental transfer of antibody.
ROTAVIRUSES
• Asymptomatic infections are common,
especially in adults. Many cases and
outbreaks are nosocomial
• Group A infections are most common.
• Group B has been associated with
outbreaks in adults in China
• Group C is responsible for sporadic cases
of diarrhea in infants around the world.
ROTAVIRUSES
• Spread is mainly person to person via
fecal - oral route and through fomites.
• Spread by food and water is also possible.
Spread via respiratory route is speculated.
• High numbers of viral particles are shed in
diarrheal stools.
ROTAVIRUSES
• Fever- can be high grade (>102° F in 30%
of patients)
• Vomiting, nausea precedes diarrhea.
• Diarrhea is usually watery (no blood or
leukocytes), lasting 3-9 days, but longer in
malnourished and immune deficient
individuals. Necrotizing entercocolitis and
hemorrhagic gastroenteritis is seen in
neonates
ROTAVIRUSES
• Dehydration is the main contributor to
mortality.
• Secondary malabsorption of lactose and
fat, and chronic diarrhea are possible
ROTAVIRUSES- DX
• Rapid diagnosis - antigen detection in
stool by ELISA (uses a monoclonal
antibody) and LA
ROTAVIRUSES- Tx
• Supportive - rehydration (oral /
intravenous)
• Antiviral agents not known to be effective
NORWALK VIRUS AND
NORWALK-LIKE VIRAL AGENTS
• First detected in stools of patients with
gastroenteritis in Norwalk, Ohio in 1972.
NORWALK VIRUS AND
NORWALK-LIKE VIRAL AGENTS
•
•
•
•
Adults and children are affected
Relatively short incubation period: <24 hours
Illness is short (<3 days)
Nausea, vomiting, abdominal cramping and
watery diarrhea accompanied by headache,
fever and malaise
• Outbreaks often occur in institutions, cruise
ships, etc. through contaminated food or water
• Feco-oral spread, perhaps also spread through
vomitus
Rhinoviruses
• Rhinoviruses are one of the families of
viruses that can cause the common cold
although many other viruses can infect the
respiratory tract and cause cold-like
symptoms.
• It is estimated that about one third of
"colds" are caused by rhinovirus
infections.
Rhinoviruses
• Spread by aerosols - can also be spread
by fomites such as hands and other forms
of direct contact.
• Rhinoviruses are quite stable, lasting for
hours on fomites, but are sensitive to
temperature.
Rhinoviruses
• The symptoms of a rhinovirus infection are
well known: discharging or blocked nasal
passages often accompanied by
sneezes, and perhaps a sore throat.
• Rhinorhea may be accompanied by a
general malaise, cough, sore throat etc.
• The characteristic symptoms occur from
one to four days after infection
Rhinoviruses
• Rhinovirus infections usually occur at times of
increased human contact, that is in the colder
months of the year.
• Many different serotypes circulate
simultaneously.
• Frequently children become infected and then
pass the virus to adults after an incubation time
of about two or three days.
• Often as many as one half of the contacts get a
cold in this way.
Rhinoviruses
• Many infections by other viruses cause
symptoms that are similar to those of
rhinoviruses. These include
parainfluenzaviruses, coronaviruses and
enteroviruses
HEPATITIS VIRUSES
• Several diseases of the liver, collectively
known as hepatitis, are caused by viruses
Hepatitis A
• Hepatitis A virus causes infectious hepatitis
which is transmitted via the oral-fecal route as a
result of close contact such as in day-care
centers.
• The virus is also spread by sexual contact and in
contaminated food.
• Rarely (in fewer than 1% of cases) is HAV
spread by blood products, blood transfusions or
intravenous drug use.
Hepatitis A
• The most obvious symptom is jaundice.
• HAV also causes abdominal pain, nausea
and diarrhea.
• In addition, the patient may suffer fatigue
and fever.
• Chronic infections with HAV do not occur
but some patients may experience
symptoms for up to 9 months.
Hepatitis A
• An ELIZA test for anti-HAV IgM is
available.
• Diagnosis is also made from the
symptoms and the clusters of cases that
occur.
• The presence of IgG within the first few
weeks of infection suggests a prior
infection or vaccination.
Hepatitis A
• There is no treatment.
• Supportive care should be given.
• Hepatitis A immune globulin can be
administered early after infection (two
weeks) and gives some temporary
immunity (up to five months).
SERUM HEPATITIS –
HEPATITIS B
• HBV is found worldwide and is a major
cause of hepatocellular carcinoma
• Serum hepatitis is usually first diagnosed
from the clinical symptoms.
• Liver enzymes are also detected in the
bloodstream during the symptomatic
phase
SERUM HEPATITIS –
HEPATITIS B
• Supportive care is the major treatment.
• Anti-HBV immune globulin is effective
soon after exposure.
• It can also be given neonatally to children
of HBsAg-positive mothers.
Hepatitis B Tx/Prevention
• There are three FDA-approved drugs for
treating hepatitis B.
– Interferon-alpha 2b (Intron A)
– Hepsera (Adefovir Dipivoxil)
– Lamivudine (Epivir HBV)
– Vaccination is the best prevention
NON-A, NON-B HEPATITIS
(NANBH) - HEPATITIS C
• HCV is found worldwide with the highest
incidence in southern and central Europe,
the Middle East and Japan.
• Symptoms, when they occur, extend from
one to more than five months after
infection; virus is detectable in the
bloodstream during this period.
NON-A, NON-B HEPATITIS
(NANBH) - HEPATITIS C
• Symptoms are the first aspect of
diagnosis.
• These include jaundice, nausea and
fatigue accompanied by elevated (at least
ten fold) alanine aminotransferase.
NON-A, NON-B HEPATITIS
(NANBH) - HEPATITIS C
• Antibodies against HCV are also clearly
indicative.
• There is a highly specific ELIZA test that
detects HCV antibodies; however, these
do not appear until eight to twenty weeks
after infection which is after the end of the
prodromal phase.
NON-A, NON-B HEPATITIS
(NANBH) - HEPATITIS C
• The patient should be assessed for chronic liver
disease and counseled to avoid behavior, such
as alcohol consumption, that may exacerbate
liver damage.
• Two drugs in combination are recommended in
a 24-48 week regimen. These are ribavirin and
pegylated interferon alpha-2a and 2b
(Peginterferon which has the trade names
Pegintron (Schering-Plough) and Pegasys
(Roche).
Rabies
• Rabies virus belongs to the family:
Rhabdoviridae
• Rabies is spread, usually by bites from
animals, to other animals and to man. It is
thus a zoonotic infection.
• Vaccination of animals has reduced the
rate of human disease and in the United
States there is approximately one case of
human rabies per year.
Rabies
• Vaccination, even after exposure, is extremely
effective at preventing disease.
• Without such treatment, rabies is almost
invariably fatal.
• The patient should receive the vaccine on first
visit and day 3,7,14,28 and the rabies IG after
exposure. Half of the RIG should be given
around the site of the bite/scratch. Dose
20units/kg
•
ARBOVIRUSES
• The term arboviruses is used to describe
viruses from various families which are
transmitted via arthropods.
• Diseases caused by arboviruses include
encephalitis, febrile diseases (sometimes
with an associated rash), and hemorrhagic
fevers
ARBOVIRUS-ASSOCIATED
ENCEPHALITIS
• California serogroup / La Crosse
encephalitis
• St. Louis encephalitis
• Eastern equine encephalitis
• Western equine encephalitis
• Venezuelan equine encephalitis
• West Nile encephalitis
ARBOVIRUSES ASSOCIATED WITH FEVER OR
HEMORRHAGIC FEVER
• Colorado tick fever
• DENGUE VIRUS
• YELLOW FEVER VIRUS (hemorrhagic
fever)
– found in Africa and South America
Colorado tick fever
• Occurs in the Rocky Mountain States.
• It is a mild disease resulting in fever,
headache, myalgia and often rash.
• The virus is transmitted by ticks.
• In diagnosis, the physician must consider
the much more serious Rocky Mountain
spotted fever (rickettsial disease) which
may have similar initial symptoms
Dengue fever
• One of the more rapidly increasing diseases in
the tropics and occurs worldwide (50-100 million
cases per year).
• Every year there are cases of dengue fever
imported by travelers into the United States.
• Usually illness is ~1-8 days after infection and
IgM may not be present until somewhat later.
• The infection can sometimes progress to
encephalitis/encephalopathy.
Dengue Hemorrhagic Fever (DHF)
• potentially deadly complication of dengue
• A large subcutaneous hemorrhage on the upper arm of a
patient with dengue hemorrhagic fever
Dengue Hemorrhagic Fever (DHF)
• This is a disease that is only found in
Africa and South America.
• Infection results in severe systemic
disease, hemorrhages, degeneration of
the liver, kidney and heart.
• The case-fatality rate can be 50%.
• There is an effective vaccine (attenuated
strain called 17D).
Ebola Virus
Ebola is a virus-caused
disease limited to parts
of Africa. Within a week,
a raised rash, often
hemorrhagic (bleeding),
spreads over the body.
Bleeding from the mucous
membranes is typical causing
apparent bleeding from the
mouth, nose, eyes and rectum.
Ebola Virus
• The exact mode of transmission is not
understood.
• The incubation period appears to be up to
1 week, at which time the patient develops
fatigue, malaise,headache, backache,
vomiting, and diarrhea.
Ebola Virus
• Within a week, a raised (papular) rash
appears over the entire body.
• The rash is often hemorrhagic.
• Hemorrhaging generally occurs from the
gastrointestinal tract, causing the patient
to bleed from both the mouth and rectum.
• Mortality is high, reaching 90%. Patients
usually die from shock rather than blood
loss.
QUESTIONS????