Download 15 Virus transcript

Survey
yes no Was this document useful for you?
   Thank you for your participation!

* Your assessment is very important for improving the work of artificial intelligence, which forms the content of this project

Document related concepts

Vectors in gene therapy wikipedia, lookup

DNA virus wikipedia, lookup

Viral phylodynamics wikipedia, lookup

Transcript
Viruses
Cause many infections of humans, animals, plants, and bacteria
Cannot carry out any metabolic pathway
Neither grow nor respond to the environment
Cannot reproduce independently
Obligate intracellular parasites
Characteristics of Viruses
Cause most diseases that plague industrialized world
Virus – miniscule, acellular, infectious agent having one or several pieces of either DNA
or RNA
No cytoplasmic membrane, cytosol, or organelles
Have extracellular and intracellular state
Extracellular state
Called virion
Protein coat (capsid) surrounding nucleic acid
Nucleic acid and capsid also called nucleocapsid
Some have phospholipid envelope
Outermost layer provides protection and recognition sites for host cells
Intracellular state
Capsid removed
Virus exists as nucleic acid
How Viruses Are Distinguished
Type of genetic material they contain
Kinds of cells they attack
Size of virus
Nature of capsid coat
Shape of virus
Presence or absence of envelope
Genetic Material of Viruses
Show more variety in nature of their genomes than do cells
May be DNA or RNA; never both
Primary way scientists categorize and classify viruses
Can be double stranded (ds) or single stranded (ss) so they are called dsDNA, ssDNA,
dsRNA, or ssRNA
Much smaller than even a gene of a host cell!
Hosts of Viruses
Most are very host-specific: Most only infect particular kinds of host cells
1
Due to affinity of viral surface proteins for complementary proteins on host cell surface
A few are generalists – infect many kinds of cells in many different hosts
Capsid Morphology
Capsids – protein coats that provide protection for viral nucleic acid and means of
attachment to host’s cells
Capsid composed of proteinaceous subunits called capsomeres
Come capsids composed of single type of capsomere; other composed of multiple types
The Viral Envelope
Acquired from host cell during viral replication or release; envelope is portion of
membrane system of host
Composed of phospholipid bilayer and proteins; some proteins are virally-coded
glycoproteins (spikes)
Envelope’s proteins and glycoproteins often play role in host recognition
Viral Replication
Dependent on host’s organelles and enzymes to produce new virions
Replication cycle may or may not result in death of host cell
Stages of lytic replication cycle
Attachment
Entry
Synthesis
Assembly
Release
Attachment of Animal Viruses
Chemical attraction
Animal viruses do not have tails or tail fibers
Have glycoprotein spikes or other attachment molecules that mediate attachment
Synthesis of Animal Viruses
Each type of animal virus requires different strategy depending on its nucleic acid
Must consider
How mRNA is synthesized?
What serves as template for nucleic acid replication?
Assembly and Release of Animal Viruses
Most DNA viruses assemble in and are released from nucleus into cytosol
Most RNA viruses develop solely in cytoplasm
Number of viruses produced and released depends on type of virus and size and initial
health of host cell
Enveloped viruses cause persistent infections
Naked viruses released by exocytosis or may cause lysis and death of host cell
2
Release
Enveloped and Naked
Lysis
Exocytosis
Enveloped
Budding
Latency of Animal Viruses
When animal viruses remain dormant in host cells
May be prolonged for years with no viral activity, signs, or symptoms
Some latent viruses do not become incorporated into host chromosome
When provirus is incorporated into host DNA, condition is permanent; becomes
permanent physical part of host’s chromosome
The Role of Viruses in Cancer
Normally, animal’s genes dictate that some cells can no longer divide and those that can
divide are prevented from unlimited division
Genes for cell division “turned off” or genes that inhibit division “turned on”
Neoplasia – uncontrolled cell division in multicellular animal; mass of neoplastic cells is
tumor
Benign vs. malignant tumors
Metastasis
Cancers
How Viruses Cause Cancer
Some carry copies of oncogenes as part of their genomes
Some stimulate oncogenes already present in host
Some interfere with tumor repression when they insert into host’s repressor gene
Several DNA and RNA viruses are known to cause ~15% of human cancers
Burkitt’s lymphoma
Hodgkin’s disease
Kaposi’s sarcoma
Cervical cancer
Culturing Viruses in the Laboratory
In Whole Organisms
Bacteria
Plants and Animals
Embryonated Chicken Eggs
In Cell (Tissue Culture)
3
Prion
A prion is an infectious agent composed of protein in a misfolded form.
This is in contrast to all other known infectious agents (virus/bacteria/fungus/parasite)
which must contain nucleic acids (either DNA, RNA, or both).
All known prion diseases affect the structure of the brain or other neural tissue and all are
currently untreatable and universally fatal.
Prions are responsible for "mad cow disease" in cattle and Creutzfeldt–Jakob disease
(CJD) in humans.
Prion Diseases
Cattle
Bovine spongiform encephalopathy (BSE; Mad Cow Disease)
Humans
Creutzfeldt–Jakob disease (CJD)
Degenerative brain disease, incurable and fatal
Can get it from use of contaminated brain products such as Human Growth Hormone
obtained from the pituitary glands of persons who died from Creutzfeldt–Jakob Disease
Kuru
From cannibalism. Called Laughing Sickness; tremors are also classic symptoms
All involve fatal neurological degeneration, deposition of fibrils in brain, and loss of
brain matter
Large vacuoles form in brain; characteristic spongy appearance
Spongiform encephalopathies (causes holes in the brain)
Only destroyed by incineration; not cooking or sterilization
Kuru
Kuru is an incurable degenerative neurological disorder caused by a prion found in
humans.
The term "kuru" derives from the Fore word "kuria/guria" ("to shake"), a reference to the
body tremors that are a classic symptom of the disease
It is now widely accepted that Kuru was transmitted among members of the Fore tribe of
Papua New Guinea via cannibalism.
It is also known among the Fore as the laughing sickness due to the pathologic bursts of
laughter people would display when afflicted with the disease.
DNA Viruses
Classified based on the type of DNA they contain, the presence or absence of an
envelope, size, and the host cells they attack
Contain either double-stranded DNA (dsDNA) or single-stranded DNA (ssDNA) for their
genome
Double-stranded DNA viruses
Poxviridae, Herpesviridae, Papillomaviridae, Hepadnoviridae, and Adenoviridae
4
Poxviridae
Smallpox
Herpesviridae
Cold sores, chicken pox, mononucleosis
Papillomaviridae
Warts
Hepadnoviridae
Hepatitis B
Adenoviridae
Common cold, pink eye
Poxviridae
Double-stranded DNA viruses
Have complex capsids and envelopes
Largest viruses
Infect many mammals
Most animal poxviruses are species specific
Unable to infect humans because they cannot attach to human cells
Infection occurs primarily through the inhalation of viruses
Close contact is necessary for infection by poxviruses
Smallpox and molluscum contagiosum are the two main poxvirus diseases of humans
Some diseases of animals can be transmitted to humans
All poxviruses produce lesions that progress through a series of stages
Smallpox
In the genus Orthopoxvirus
Commonly known as variola
Exists in two forms
Variola major causes sever disease that can result in death
Variola minor causes a less severe disease with a much lower mortality rate
Both forms infect internal organs and then move to the skin where they produce pox
Scars result on the skin, especially on the face
There are a number of factors that allowed eradication of smallpox
Inexpensive, stable, and effective vaccine
No animal reservoirs
Obvious symptoms allow for quick diagnosis and quarantine
Lack of asymptomatic cases
Virus is only spread via close contact
5
Smallpox as a Bioweapon
can be produced in large quantities
stable for storage and transport
stable in aerosolized form (up to 2 days)
high mortality
highly infectious (person-to-person spread)
most of the world has little to no immunity
Therapy/Prevention of Smallpox
Vaccination
vaccination stopped in 1979 (1972 in U.S.)
last case in U.S. 1949
2 million deaths Worldwide in 1967
Vaccinia virus
leaves scar
Supportive therapy – no effective antiviral once infected
Molluscum Contagiosum
Caused by Molluscipoxvirus
Spread by contact among infected children
Sexually active adults can sometimes contract a genital form of the disease
Skin disease characterized by smooth, waxy, tumor-like nodules on the face, trunk, and
limbs
Virus produces a weak immune response
Causes neighboring cells to divide rapidly thus acting like a tumor-causing virus
Other Poxvirus Infections
Poxvirus infections also occur in animals
Transmission of these poxviruses to humans require close contact with infected animals
Infections of humans are usually mild
Can result in pox and scars but little other damage
Cowpox was used by Edward Jenner to immunize individuals against smallpox
Herpesviridae
Viruses attach to a host cell’s receptor and enter the cell through the fusion of its envelope
with the cell membrane
Herpesviruses can have latency
They may remain inactive inside infected cells
Viruses may reactivate causing a recurrence of manifestations of the disease
Herpesviruses include various genera
Simplexvirus, Varicellovirus, Lymphocryptovirus, Cytomegalovirus, Roseolovirus
6
Herpesviruses are also designated by “HHV” (for “human herpesvirus”) and a number
indicating the order in which they were discovered
“Newer” nomenclature of the Herpesviridae
HHV1 = HSV1 (Herpes simplex 1; cold sores)
HHV2 = HSV2 (Herpes simplex 2; STD)
HHV3 = VZV (varicella-zoster; chicken pox)
HHV4 = EBV (Epstein-Barr virus)
HHV5 = CMV (cytomegalovirus)
HHV6 = roseola infantum (major cause)
HHV7 = roseola infantum (minor cause)
HHV8 = KS (Kaposi’s sarcoma)
Herpes Simplex Infections
Often result in slowly spreading skin lesions
Viruses of this genus are commonly known as herpes simplex virus or HSV
2 species of herpes simplex
Herpes simplex virus type 1 (HSV-1)
Herpes simplex virus type 2 (HSV-2)
Epidemiology and Pathogenesis of HSV Infections
Active lesions are the usual source of infection
Aysmptomatic carriers can shed HSV-2 genitally
Transmission of the viruses occurs through close bodily contact
Viruses enter the body through cracks or cuts in mucous membranes
Skin lesions result from inflammation and cell death at the site of infection
Herpes virions can spread from cell to cell through the formation of syncytia
Epidemiology and Pathogenesis of HSV Infections
HSV-1 infections typically occur via casual contact in children
HSV-2 infections are acquired between the ages of 15 and 29 from sexual activity
Herpes infections often result in the recurrence of lesions
Up to two-thirds of patients experience recurrences due to activation of the latent virus
Diagnosis, Treatment, and Prevention
Diagnosis
Characteristic lesions, especially in the genital region and on the lips, is often diagnostic
HSV infections are among the few viral diseases that can be controlled with
7
chemotherapeutic agents
Topical applications of the drugs limit the duration of the lesions and reduce viral
shedding
The drugs don’t cure the diseases or free nerve cells of latent viral infections
Varicella-Zoster Virus Infections
Commonly referred to as VZV
Causes two diseases
Varicella
Often called chicken pox
Typically occurs in children
Herpes zoster
Also called shingles
Usually occurs in adults
Epidemiology and Pathogenesis of VZV Infections
Chickenpox is a highly infectious disease seen most often in children
Viruses enter the skin through the respiratory tract and the eyes
Virus replicate at the site of infection then travel via the blood throughout the body
Chickenpox in adults is typically more severe than the childhood illness
Epidemiology and Pathogenesis of VZV Infections
Latent virus can reactivate producing a rash known as shingles
The rash is characteristic for its localization along a dermatome - dorsal roots from the
spine
Epstein-Barr Virus Infections
Also referred to as EBV or HHV-4
Can cause a number of different diseases
Epidemiology and Pathogenesis of EBV Infections
Transmission of EBV usually occurs via saliva
Virions initially infect the epithelial cells of the pharynx and parotid salivary glands
The virus then enters the bloodstream where it invades the B lymphocytes
Epidemiology and Pathogenesis of EBV Infections
The viruses become latent in B cells and immortalize them by suppressing apoptosis
Symptoms of infectious mononucleosis arise from the immune response
Cytotoxic T cells kill virus infected B lymphocytes
Cancer development appears to depend in part on various cofactors
Extreme diseases arise in individuals with T cell deficiency
Such individuals are susceptible because infected cells are not removed by cytotoxic T
8
cells allowing the virus to proliferate
Cytomegalovirus
Also referred to as CMV
Cells infected with this virus become enlarged
CMV infections is one of the more common infections of humans
Transmission occurs through bodily secretions
Requires close contact and a large exchange of secretion
Usually occurs via sexual intercourse
Also transmitted by in utero exposure, vaginal birth, blood transfusions, and organ
transplants
Most CMV infections are asymptomatic
CMV causes infectious mononucleosis (second to EBV)
Fetuses, newborns, and immunodeficient patients can develop complications
CMV can cause birth defects and may result in death
AIDS patients or other immunocompromised adults may develop pneumonia, blindness,
or cytomegalovirus mononucleosis, which is similar to infectious mononucleosis
Other Herpesvirus Infections
Human herpesvirus 6 (HHV-6)
In the genus Roseolovirus
Causes roseola which is characterized by a pink rash on the face, neck, trunk, and thighs
Linked to multiple sclerosis by some researchers
Can cause mononucleosis-like symptoms
Infection with HHV-6 may make individuals more susceptible to AIDS
Human herpesvirus 8 (HHV-8)
Causes Kaposi’s sarcoma, a cancer seen in AIDS patients
The virus is not found in cancer-free patients or in normal tissues of victims
Papillomavirus Infections
Causes papillomas, commonly known as warts
Benign growths of the epithelium of the skin or mucous membranes
Papillomas form on many body surfaces
Often painful and unsightly
HPV Type 1 (feet)
HPV Type 2 (hands)
HPV Type 16 and 18 (cervical cancer)
HPV Type 6 and 11 (genital warts)
Epidemiology and Pathogenesis of Papillomavirus Infections
Types 1 and 2 (hands and feet) enter through a tiny break in the skin
9
Genital warts are transmitted via direct contact
All types spread by autoinoculation
Genital warts are a common sexually transmitted disease and are associated with an
increased risk of cancer
Diagnosis, Treatment, and Prevention
Diagnosis
Usually based on observation of the papillomas and pin-point bleeding upon debridement
of callous on top. The warts are angiotrophic, so they pull little blood vessels into the
epidermis to feed them.
Diagnosis of cancers results from inspection of the genitalia and by a PAP smear in
women
Treatment
Some warts can be removed through various methods (laser is best since it cauterizes the
wound so viruses cannot escape and migrate to a new area). However, they frequently
come back.
Treatment of cancers involves radiation and chemical therapy
Prevention
Prevention of common skin warts is difficult
Wear gloves when doing jobs that might nick the skin
Wear shoes so tiny cuts don’t occur
Genital warts can be prevented by abstinence and perhaps safe sex
HPV vaccine
2006 - Advisory committee on immunization practices (ACIP) recommended the HPV
vaccine
recommended for girls/women 9-26 yrs old
before sexual contact
recommended at 11-12 years of age
vaccine (Gardasil) protects against strains HPV 6, 11, 16, and 18
Hepadnoviridae
Hepatitis B
Symptoms include loss of appetite, nausea, vomiting, body aches, mild fever, dark urine,
jaundice.
Can also cause cancer in people with cirrhosis of the liver.
Therefore, it is an oncovirus. There are seven human oncoviruses.
Hepatitis B
This is the viral hepatitis that is primarily spread by sexual contact (it is
PRIMARILY a sexually transmitted disease) or sharing needles by drug users.
Only about 50% of infected persons have flu-like symptoms, including fatigue, fever,
10
headache, nausea, vomiting, muscle aches, and dull pain in the upper right of the
abdomen.
Jaundice, a yellowish cast to the skin, can also be present. Some persons have an acute
infection that lasts only three to four weeks.
Others have a chronic form of the disease that leads to liver failure and a need for a
liver transplant.
Since there is no treatment for an HBV infection, prevention is imperative by a
vaccine, which is safe and does not have any major side effects.
This vaccine is now on the list of recommended immunizations for children.
Adenoviridae
One of the causative agents of the common cold
Spread via respiratory droplets
Respiratory infections
Viruses are taken into cells lining the respiratory tract via endocytosis
Symptoms include sneezing, sore throat, cough, headache, and malaise
Infection of the intestinal tract can produce mild diarrhea
Infection of the conjunctiva can result in pinkeye
Adenovirus pathology
diarrhea in children
respiratory infection in children and adults
military recruits
close contact
physical activities (deep inhalation of virus into lungs)
stress
after infection, see immunity
RNA Viruses
Picornaviridae
Polio, Hepatitis A, common cold
Coronaviridae
Common cold
Calicivirus
Stomach flu
Flaviviridae
Hepatitis C
Paramyxovirus
Measles, mumps
11
Orthomyxovirus
Influenza
Rhabdoviridae
Rabies
Filoviridae
Hemorrhagic Fever
Reoviridae
Stomach flu
Togaviridae
German Measles
Positive RNA acts like mRNA and can be used by a ribosome to translate protein
Negative RNA must first be transcribed as mRNA to be processed by a ribosome
RNA viruses are categorized by their genomic structure, the presence of an envelope, and
the size and shape of their capsid
Picornaviridae
Enteroviruses
Polio
Hepatitis A
Rhinovirus
Enteroviruses
Found
in respiratory secretions
stool of an infected person
Parents, teachers, and child care center workers may also become infected by
contamination of the hands with stool from an infected infant or toddler during diaper
changes.
Poliomyelitis
First described by Michael Underwood in 1789
First outbreak described in U.S. in 1843
21,000 paralytic cases reported in the U. S. in 1952
Global eradication in near future
Enterovirus (RNA)
Three serotypes: 1, 2, 3
Minimal immunity between serotypes
Rapidly inactivated by heat, formaldehyde, chlorine, ultraviolet light
Most poliovirus infections are asymptomatic
12
Poliomyelitis Pathogenesis
Fecal oral entry
Replication in pharynx, GI tract, local lymphatics
Hematologic spread to lymphatics and central nervous system
Viral spread along nerve fibers
Destruction of motor neurons
Rhinovirus
 Direct person-to-person contact is the most common means of transmission
 Individuals can acquire some immunity against serotypes that have infected them
in the past
◦ As a result, the number of infections tends to decrease with age
Diseases of Coronaviruses
Diarrhea
Running
nose
Sputum
Fever
100
90
80
70
60
50
40
30
20
10
0
Headache
Named due to the corona-like halo formed by their envelopes
Transmitted via large droplets from the upper respiratory tract
Second most common cause of colds
Can cause gastroenteritis in children
Diseases are mild
No treatment or vaccine is available
Myalgia






 Norwalk – genus name for original Norwalk virus and other Norwalk-like viruses.
Family Calicivirus.
 Calicivirae found worldwide, infecting humans, primates, and cattle, among
others.
 Increasingly being recognized as leading cause of food borne illness.
 Virus first identified in Norwalk, Ohio, 1973.
 Noted to commonly be a problem on cruise ships.
13
 Associated with contaminated food or water supplies.
 Noroviruses found in stool and vomit of infected.
 Very contagious – infection via eating contaminated food, contact with sick
individual or contaminated surfaces.
 Acute gastroenteritis.
 Illness begins suddenly, from 12-48 hours after ingestion. Brief illness period.
 Very young, elderly, and those with weakened immune systems may experience
more severe symptoms.
 Infectiousness may last up to 2 weeks, no evidence of long-term carriers.
Measles




One of five classical childhood diseases
Spread in the air via respiratory droplets
Viral spread requires large, dense populations of people
Viruses infect the respiratory tract and then spread throughout the body
 Characteristic lesions called Koplik’s spots appear on the mucous membrane of
the mouth
 Lesions then appear on the head and spread over the body




Highly contagious viral illness
First described in 7th century
Near universal infection of childhood in prevaccination era
Common and often fatal in developing areas




Paramyxovirus (RNA)
Hemagglutinin important surface antigen
One antigenic type
Rapidly inactivated by heat and light




Respiratory transmission of virus
Replication in nasopharynx and regional lymph nodes
Primary viremia 2-3 days after exposure
Secondary viremia 5-7 days after exposure with spread to tissues
 Incubation period 10-12 days
 Prodrome
◦ Stepwise increase in fever to
103°F or higher
◦ Cough, coryza, conjunctivitis
◦ Koplik spots (rash on mucous membranes)
14
Coryza = Head cold
 Rash
◦
◦
◦
◦
◦
2-4 days after prodrome, 14 days after exposure
Maculopapular, becomes confluent
Begins on face and head
Persists 5-6 days
Fades in order of appearance
Measles Complications
Condition
Percent reported
8
7
6
0.1
18
0.2
Diarrhea
Otitis media
Pneumonia
Encephalitis
Hospitalization
Death
Based on 1985-1992 surveillance data
 Isolation of measles virus from a clinical specimen (e.g., nasopharynx, urine)
 Significant rise in measles IgG by any standard serologic assay (e.g., EIA, HA)
 Positive serologic test for measles IgM antibody
Measles - United States, 1950-2007
Cases (thousands)
900
800
700
600
Vaccine Licensed
500
400
300
200
100
0
1950
1960
1970
1980
1990
2000
Measles, mumps, rubella vaccine
 12 months is the recommended and minimum age
 MMR given before 12 months should not be counted as a valid dose
 Revaccinate at 12 months of age or older
15
Adults at increased risk of Measles
 College students
 International travelers
 Healthcare personnel
 All persons who work in medical facilities should be immune to measles
Mumps
 Acute viral illness
 Parotitis and orchitis described by Hippocrates in 5th century BCE
 Viral etiology described by Johnson and Goodpasture in 1934
 Frequent cause of outbreaks among military personnel in prevaccine era




Paramyxovirus
RNA virus
One antigenic type
Rapidly inactivated by chemical agents, heat, and ultraviolet light




Respiratory transmission of virus
Replication in nasopharynx and regional lymph nodes
Viremia 12-25 days after exposure with spread to tissues
Multiple tissues infected during viremia
CNS involvement
15% of clinical cases
Orchitis
20%-50% in post- pubertal
males
Pancreatitis
2%-5%
Deafness
1/20,000
Death
Average 1 per year
(1980 – 1999)
Mumps—United States, 1980-2007
14000
12000
Cases
10000
8000
6000
4000
2000
0
1980
1985
1990
1995
2000
2005
Year
16
Mumps Clinical case definition
Acute onset of unilateral or bilateral tender, self-limited swelling of the parotid or other
salivary gland lasting more than 2 days without other apparent cause
 Bronchiolitis is acute inflammation of the airways, characterised by wheeze
 Bronchiolitis can result from a viral infection
 Respiratory Syncytial Virus (RSV) may be responsible for up to 90% of
bronchiolitis cases in young children
 Diagnosis is based on the signs of respiratory distress verified by immunoassay
 Treatment is supportive
 Ribavirin is used to treat extreme cases
Influenza




Caused by two species of orthomyxovirus, designated types A and B
Infection occurs primarily through inhalation of airborne viruses
Rarely attack cells outside the lungs
Death of the epithelial cells infected with influenza viruses eliminate the lungs
first line of defense against infections, the epithelial lining
 Flu patients become more susceptible to secondary bacterial infections
Transmission
 AEROSOL
◦ 100,000 TO 1,000,000 VIRIONS PER DROPLET
 18-72 HR INCUBATION
 SHEDDING
Symptoms
 FEVER
 HEADACHE
 MYALGIA
 COUGH
 RHINITIS
 OCULAR SYMPTOMS
Clinical findings
 SEVERITY
◦ VERY YOUNG
◦ ELDERLY
◦ IMMUNO-COMPROMISED
◦ HEART OR LUNG DISEASE
17
Pulmonary Complications
 CROUP (YOUNG CHILDREN)
 PRIMARY INFLUENZA VIRUS PNEUMONIA
 SECONDARY BACTERIAL INFECTION
◦ Streptococcus pneumoniae
◦ Staphlyococcus aureus
◦ Hemophilus influenzae
Reye’s Syndrome
 liver - fatty deposits
 brain - edema
 vomiting, lethargy, coma
 risk factors
◦ youth
◦ certain viral infections (influenza, chicken pox)
◦ aspirin
Non-Pulmonary Complications
 cardiac complications
 encephalopathy
 liver and CNS
◦ Reye’s syndrome
 peripheral nervous system
◦ Guillian-Barré syndrome
Gullian-Barré Syndrome
 1976/77 swine flu vaccine
◦ 35,000,000 doses
 354 cases of GBS

28 GBS-associated deaths

recent vaccines much lower risk
Mortality
 MAJOR CAUSES OF INFLUENZA VIRUS- ASSOCIATED DEATH
◦ BACTERIAL PNEUMONIA
◦ CARDIAC FAILURE
 90% OF DEATHS IN THOSE OVER 65 YEARS OF AGE
Antigenic Drift
 HA and NA accumulate mutations
18
◦
RNA virus
 immune response no longer protects fully
 sporadic outbreaks, limited epidemics
Figure 25.39
•
“new” HA or NA proteins
•
pre-existing antibodies do not protect
•
may get pandemics
Figure 25.39
Influenza Epidemiology
19
•
Influenza A has wide host range
– Birds (natural), sea mammals, horses, pigs, humans
• Strains are described by antigenicity of HA and NA, which are designated by
numbers
• Currently 15 HA (1-15) and 9 NA (1-9) described
– 1918 “Spanish flu” pandemic – H1N1
– 1957 “Asian flu” epidemic – H2N2
– 1968 “Hong Kong flu” pandemic – H1N2
– 1977 “swine flu” epidemic – H1N1
– 1999 – current threat is H5N1, similar to 1918 strain
• Epidemiology involves close contact of humans, farm animals, and birds – this
especially in Asia
• Kills >20,000 per year in the US normally
Vaccine
 ‘BEST GUESS’ OF MAIN ANTIGENIC TYPES
◦ CURRENTLY
 type A - H1N1
 type A - H3N2
 type B
 each year choose which variant of each subtype is the best to use
for optimal protection
 inactivated
 egg grown
 sub-unit vaccine for children
 reassortant live vaccine approved 2003
◦ for healthy persons (those not at risk for complications from influenza
infection) ages 5-49 years
 REST, LIQUIDS, ANTI-FEBRILE AGENTS (NO ASPIRIN FOR AGES
6MTHS-18YRS)
 BE AWARE OF COMPLICATIONS AND TREAT APPROPRIATELY
 Rhabdoviridae
◦ Include a variety of plant and animal pathogens
◦ Rabies is the most significant pathogen
 Filoviridae
◦ Cause a number of emerging diseases
◦ Include Ebola and Marburg hemorrhagic fevers




Rabies virus is the causative agent
Classical zoonotic disease of mammals
Primary reservoir of rabies in urban areas is the dog
Bats are the source of most cases of rabies in humans
20
•
•
•
Rabies virus is the causative agent
Classical zoonotic disease of mammals
Primary reservoir of rabies in urban areas is the dog
 When the virus infects the central nervous system neurological manifestations
specific to rabies develop (such as hydrophobia)
 Death results from respiratory paralysis and other neurological complications
 Diagnosis
◦ Neurological symptoms of rabies are unique and usually sufficient
◦ By the time symptoms and antibodies occur it is too late to intervene
 Treatment
◦ Treatment of the site of infection
◦ Injection of human rabies immune globulin
◦ Vaccination with human diploid cell vaccine (HDCV)
 Viral replication and movement to the brain is slow enough to
allow effective immunity to develop before disease develops
 Prevention
◦ Vaccination of domestic dogs and cats can help control rabies
◦ Little can be done to eliminate rabies in wild animals
Hemorrhagic Fever
 Marburg virus and Ebola virus are the causative agents
 The natural reservoir and mode of transmission to humans are unknown
 Spread from person to person via contaminated bodily fluids, primarily blood, and
contaminated syringes
 The virions attack many cells of the body, especially macrophages and liver cells
 Infections results in uncontrolled bleeding under the skin and from every body
opening
 The only treatment involves fluid replacement
 Up to 90% of human victims die
Viral Structure of Ebola
 It is a member of the Filoviridae family (the only other member is Marburgvirus).
 ss, negative sense RNA
 Has a distinct characteristic “6” shape.
 First found in a province in Sudan and its neighboring country, Zaire (1976). The
Zaire outbreak 280/318 cases resulted in death. The Sudan strain caused death in
397/602 cases.
 1989: Ebola made its way to the United States. A lab worker was infected by the
monkeys he was working with (Maccaca fascicularis). Workers developed
antibodies to Ebola, but did not get sick.
21
 1994: Cote d’ Ivory- only one case here: a scientist conducted an autopsy on a
wild chimpanzee. He fell ill, but did not die.
In total, there are 4 known, documented strains of Ebola:
◦ Ebola Zaire (EBO-Z): a 90% death rate
◦ Ebola Sudan (EBO-Z): lower death rate
◦ Ebola Reston
◦ Ebola Cote d’ Ivory
All strains of Ebola are classified as Biosafety Level 4, meaning Hazmat suits, multiple
airlocks, ultraviolet light rooms. Workers must be cleared to handle BSL4.
 One of the easiest methods of transmission in Ebola is through bodily fluids
(blood, secretions).
 Handling infected animals can also lead to infection with Ebola.
 While monkeys were able to transfer Ebola between themselves via airborne
particles, this type of aerosol transfer has not been demonstrated setting in a
laboratory setting.
 Incubation periods can be anywhere from 2-21 days.
 Common symptoms include: sudden onset of fever, headaches, sore throat,
muscle pains, and intense weakness.
 More intense symptoms include: maculopapular rash, kidney/liver disfunction.
 Possible internal/external bleeding.
 Internal bleeding is caused by Ebola’s coagulpathy ability. This describes a
dysfunction in the host blood clotting system.
 When infected, host macrophages begin to express Tissue Factor (TF). TF attracts
clotting molecules from the blood, leaving the rest of the body susceptible.
 Small holes in the capillaries are then cut by Ebola. Without clotting factors, the
host bleeds continuously, dying of what some have called “a million cuts.”
 Unfortunately, no reservoirs have been identified for Ebola. Several times,
scientists have brought in rodents, bats, primates, plants, and arthropods to test for
Ebola.
 Ebola could not be detected or isolated from any of these reservoirs.
 As there is no known cure for Ebola, treatment options are very limited for
patients.
 Typically, supportive therapy is used (balancing patient’s fluids, electrolytes,
maintaining oxygen status and blood pressure).
 While there are no cures yet, that does not mean several groups are not working to
create one.
 Barrier Nursing Techniques are employed to prevent further infection. Screens are
placed around the patient’s bed.
22
 Anyone treating the patient must wear gowns, masks, and gloves.
 Any items used to treat the patient are immediately put into a sterilizing solution
afterwards.
 Changing sheets must also be done with care, to minimize the possibility of
launching airborne particles or droplets of contagious material.
 1999: BBC researchers, led by Dr. Maurice Iwu, investigated the garcin kola
plant, typically eaten in Western Africa. Medicine men in those areas had long
been using it and introduced it to the researchers. In a lab setting, the plant has
been shown to inhibit Ebola multiplication.
 2001: Mice injected subcutaneously with Ebola did not become sick, but mounted
an immune response. Serum from these mice were used to treat new mice before
or after Ebola injection. All of the mice treated with serum survived.
Reoviruses
 Cause infantile gastroenteritis
 Account for approximately 50% of all cases of diarrhea in children requiring
hospitalization
 Transmitted via the fecal-oral route
 usually self-limited
 replacement of water and electrolytes
 A vaccine is available that provides some protection but has been linked to a rare
bowel blockage condition in some children
Rotavirus
 First identified as cause of diarrhea in 1973
 Most common cause of severe diarrhea in infants and children
 Nearly universal infection by 5 years of age
 Responsible for up to 500,000 diarrheal deaths each year worldwide
Enveloped, Positive ssRNA viruses
 Togaviridae (rubella)
 Designated arboviruses because they are often transmitted by arthropods
Rubella
 Togaviridae
 “German measles’
 Rubella virus is the causative agent
 One of the five childhood diseases that produces skin lesions
 Infection begins in the respiratory system but spreads throughout the body
 Characterized by a rash of flat, pink to red spots
 Infections in children are usually not serious
 Adults can develop arthritis or encephalitis
23
 Rubella infections of pregnant women can result in congenital defects or death of
the child
 Vaccination has been effective at reducing the incidence of rubella
 From Latin meaning "little red"
 Discovered in 18th century - thought to be variant of measles
 Congenital rubella syndrome (CRS) described by Gregg in 1941




Respiratory transmission of virus
Replication in nasopharynx and regional lymph nodes
Viremia 5-7 days after exposure with spread to tissues
Placenta and fetus infected during viremia
 Incubation period 14 days
(range 12-23 days)
 Prodrome of low-grade fever
 Maculopapular rash 14-17 days after exposure
 Lymphadenopathy in second week
Epidemic Rubella, US 1964-65





12.5 million rubella cases
2,000 encephalitis cases
11,250 abortions (surgical/spontaneous)
2,100 neonatal deaths
20,000 CRS cases
◦ deaf - 11,600
◦ blind - 3,580
◦ mentally retarded - 1,800
Congenital Rubella Syndrome




Infection may affect all organs
May lead to fetal death or premature delivery
Severity of damage to fetus depends on gestational age
Up to 85% of infants affected if infected during first trimester







Deafness
Cataracts
Heart defects
Microcephaly
Mental retardation
Bone alterations
Liver and spleen damage
 Isolation of rubella virus from clinical specimen (e.g., nasopharynx, urine)
24
 Positive serologic test for rubella IgM antibody
 Significant rise in rubella IgG by any standard serologic assay (e.g., enzyme
immunoassay)
 Most reported rubella in the U.S. since the mid-1990s has occurred among
foreign-born Hispanic adult
 Majority of CRS since 1997 occurred in children of unvaccinated women born to
Hispanic women, most born in Latin America
Rubella case definition
 Acute onset of generalized maculopapular rash, and
 Temperature of >99°F (37.2 °C), if measured, and
 Arthralgia or arthritis, lymphadenopathy, or conjunctivitis
25