Transcript Stages of viral infection

Lecture 20: Infection
See Flint et al, Appendix 2
General points: A general listing of
different viral diseases that affect
different organs of the body.
Viruses infect specific
Organisms
Tissues
Effects can range from
Unnoticeable
Deadly
Routes of
viral entry
The Metazoan body plan:
We are essentially a tube.
Respiratory tract diseases
Virus induced respiratory infections kill about 1 million
children each year as well as a significant number of
older adults.
• Many of the viruses that infect only the respiratory
tract do not induce a strong immune response and
hence reinfection with the same or a similar strain is
common.
• Children get about 6 colds a year and adults get 2-3
per year.
• Deaths from respiratory infections: approx. 4.4 x
106/yr for Bact. and viruses world wide.
• Influenza- 20,000 deaths/yr in US during epidemic
years (most years), Spanish flu of 1918, 500,000 in
US 20 x 106 worlwide, Hong Kong outbreak 68-69,
34,000 in US.
• Human Respiratory Syncytial Virus- 4,500 deaths/yr
(children) in US.
Respiratory tract diseases
• Rhinitis (Common Cold)-watery nasal discharge and
obstruction, sneezing, mild sore throat and coughing
but little or no fever. Infection based in upper
respiratory. Sometimes complicated by
superinfection with bacteria. Rhinoviruses,
coronaviruses
• Pharyngitis (most are viral)-sore throat, malaise,
fever, sometimes cough. Infection based in pharynx.
Can be caused by many of the same agents that cause
common colds. RSV and adenovirus are prominent
causes in young children and Herpes type viruses in
young adults.
• Laryngotracheobronchitis (Croup)-fever, barking or
metallic cough, respiratory distress, sometimes
complete laryngeal obstruction. Most common causes
are influenza and parainfluenza virus.
Respiratory tract diseases
• Bronchiolitis-Rapid and labored breathing, persistent
cough, wheezing, cyanosis, variable amount of atelectasis,
marked emphysema. Major causes are Influenza,
parainfluenza, and RSV especially in young children. RSV
can develop virtually overnight causing SIDS in young
children.
• Pneumonia-often develops following upper resp. tract
infection. Febrile, some cough, degree of dyspnea,
wheezing, moist rales. X-rays often show only scattered
areas of consolidation and diffuse lesions unlike
pronounced lesions and consolidated areas in bacterial
pneumonia. RSV, Influenza, parainfluenza, adenoviruses
are major causes. A major cause of death to older people
and young children. RSV is the major respiratory
pathogen in young children and kills 4,500 children a year
in the U.S. alone.
Viral Gastroenteritis
• Inflammation of the stomach and intestines
• Usually manifested as diarrhea which is
watery but not bloody in the case of viral
infection.
• Fever and Vomiting common with some
infectious agents.
• Diarrheal diseases kill 3 million children each
year mostly in developing countries.
• Rotaviruses are the main culprits and are
responsible for most of the deaths.
• Astroviruses and Caliciviruses (Norwalk virus)
can also cause diarrhea.
Central Nervous system
diseases
• Most result as rare complication of primary infections
elsewhere in the body.
• Viruses may be
– neuroinvasive (able to enter the nervous system) and/or
– neurovirulent (cause nerve damage).
– e.g. Mumps is highly neuroinvasive but not very neurovirulent
while herpes is just the opposite.
• Viruses cause disease in a variety of ways
– infection of a specific area (Ammon's horn with rabies, and
temporal lobes with HSV)
– Broad infection.
• Some lyse neurons while some cause demyelination of
axons.
•
Central Nervous system
diseases
Deaths - Measles which can cause a variety of brain infections kills
about 1 million/yr worldwide, mostly in area without vaccination.
• Meningitis-Infection of meningeal cells. Viruses are major cause but
viral infection is much less severe than bacterial with full recovery
likely. Headache, Fever, and neck stiffness with/or without vomiting
and photophobia are symptoms. Mumps and Enteroviruses are most
common agents.
• Paralysis-Mostly from poliovirus in countries where the virus has not
been eradicated. Poliomyelitis involving demyelination of nerve cells.
• Encephalitis-Fever, headache, neck stiffness, vomiting, alterations in
state of consciousness indicating involvement of brain parenchymal
tissue. Patient is lethargic and confused and seizures, or paralysis
may develop before coma and death. Postinfectious EncephalitisOccurs a few days after infection of children with measles, mumps,
or varicella. Severe demyelination is observed and prognosis is grim.
Central Nervous system
diseases
• Guillain-Barre syndrome- Demyelination is common
finding. Most frequently caused by Epstein Barr
Virus (EBV) infection and appearing 1-4 weeks after
mononucleosis infection. Most recover completely but
15% have residual nerve damage.
• Reye's syndrome - Cerebral edema without
inflammation is common symptom. 25% of cases are
fatal. Follow influenza or chickenpox infection in
children and seems to be an association between
syndrome and aspirin administration.
• AIDS Dementia Complex - Results from destruction
of nerve cells often late in AIDS syndrome (HIV).
Direct destruction of nerve cells and demyelination
are involved.
Skin Rashes
• Macular-Flat colored spots;
• Papular-Slightly raised containing no
expressible fluid;
• Vesicles-blister with clear fluid from
which virus can be isolated;
• Pustular- Blisters containing puss;
• Nodular- Generally warts.
Hemorrhagic fever
• A variety of diseases that share the common
feature of widespread hemorrhages from the
bodies epithelial tissue including internal
mucosa such as the gastrointestinal tract and
the skin.
• A variety of internal damage is often
associated with the different diseases.
• Hanta virus for example causes severe renal
necrosis.
• Other agents (Ebola and Yellow fever virus)
cause severe liver damage.
• Many have high fatality rates.
Genitourinary infections
• Herpes simplex virus 2 and Papillomaviruses are the major
viruses infecting the genital area.
• Sexual transmission is the main way of acquiring the agent.
• Herpes manifests as painful itchy ulcerated vesicular lesions
occasionally accompanied by fever and malaise especially in
woman. Spread to the central nervous system occurs in 10% of
cases with mild meningitis resulting. Recurrences are common
although generally less severe than the initial infection.
• Papillomaviruses: Genital warts. Warts appear as external
condyloma and usually disappear without treatment within a
couple of years. Certain types of HPV may progress over several
years through stages of cervical intraepithelial neoplasia (CIN)
to invasive squamous cell carcinoma.
• HIV: Deaths by HIV-about 1 million/yr worldwide, 20,000/yr in
US although was much higher before triple drug therapy
Eye diseases
• A number of common childhood viral diseases can
involve conjunctivitis
– Inflammation of the conjunctiva which is the
transparent membrane covering the sclera i.e. white of
the eye and the inner eyelid).
– Results in redness, discomfort and discharge and is
commonly called pink eye. Some types are particularly
dangerous, especially those involving the cornea
(keratoconjunctivitis).
• Herpes Simplex Virus (HSV) is the commonest
infectious agent that causes blindness in the
Western world.
• A number of eye diseases, e.g. cataracts,
glaucoma, and retinopathy are associated with
congenital rubella syndrome and cytomegalic
inclusion disease of infants.
Viral arthritis
• Stiff and painful joints.
• Usually accompanied by fever and myositis
(inflammation of muscle tissue causing pain
tenderness and weakness)
• Can occur with or without rash.
• Rarely persists for more than a few weeks.
• Major causative agents are certain toga-,
flavi-, and bunyaviruses (arboviruses).
• It has been hypothesized that rheumatoid
arthritis may have a viral origin.
Viral Carditis
• Myocarditis = inflammation of the heart
muscle
• Pericarditis = inflammation of pericardium
membrane that encloses he heart
• Cardiomyopathy = diseases causing reduction
in the force of the heart
• Associated with certain enteroviruses (family
of picornaviruses), most notably coxsackie B
virus.
• Infections often reoccur, leading to
permanent myocardial damage, cardiomegaly
(enlarged heart), or congestive cardiac
failure.
Viral Hepatitis
• Inflammation of the liver with accompanying liver cell
damage.
• 20-30 cases per 100,000 people per year in the U.S.
• Symptoms :jaundice often proceeded by flu-like illness.
• Liver failure can occurs.
• Can become chronic depending on the infectious agent
and cirrhosis
• Transmission:
– parenteral (needle infection usually),
– perinatal (occurring just before or after birth),
– sexual, or enteric (via gut cells).
• 5 viruses known to infect the liver as the primary organ.
Other viruses can also cause hepatitis e.g. Herpes
viruses and some viruses causing hemorrhagic fever.
• Deaths- Hepatitis B is the most common killer killing 2
million/yr worldwide and 5000/yr in US.
Viral pancreatitis and diabetes
• Mumps infection can be complicated by
severe pancreatitis (inflammation of the
pancreas).
• Can also be caused by certain other
enteroviruses.
• There is some evidence that viral
infections triggers insulin-dependent
juvenile diabetes mellitus.
Chronic fatigue syndrome
• Characterized by extreme fatigue.
• EBV, Coxsackie B, CMV, and HTLV are
among the many viruses to be isolated
from such patients
• Importantly, no cause-effect
relationship has been established
Congenital and Perinatal
Infections
• Include a variety of diseases acquired
– Prenatally,
– Intrapartum (during birth process) or
– Postnatally within the first few weeks.
• Can be particularly dangerous since the
newborn is not protected by the
mothers antibodies