Viruses.

Viruses

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

Sizes of Viruses Figure 13.4

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 dsDNA, ssDNA, dsRNA, ssRNA May be linear and composed of several segments or single and circular Much smaller than genomes of cells

Hosts of Viruses Most only infect particular kinds of host’s cells
Due to affinity of viral surface proteins or glycoproteins for complementary proteins or glycoproteins on host cell surface May only infect particular kind of cell in host 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

Attachment

Entry/Penetration

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?

Genome Replication and Protein Synthesis
Figure 13.13

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

Release Enveloped and Naked Lysis Exocytosis

Release 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

Oncogene Theory Figure 13.15

Culturing Viruses in the Laboratory
In Whole Organisms Bacteria Plants and Animals Embryonated Chicken Eggs In Cell (Tissue Culture)

Culturing Viruses in Embryonated Chicken Eggs
Figure 13.17

Culturing Viruses in Cell (Tissue) Culture
Figure 13.18

Characteristics of Prions
Proteinaceous infectious agents Composed of single protein PrP All mammals contain gene that codes for primary sequence of amino acids in PrP Two stable tertiary structures of PrP Normal functional structure with α-helices called cellular PrP Disease-causing form with β-sheets called prion PrP Prion PrP converts cellular protein into prion PrP by inducing conformational change

Tertiary Structures of PrP
Figure 13.21

Prion Diseases 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 – BSE, CJD, kuru Only destroyed by incineration; not cooking or sterilization

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, Polyomaviridae, and Adenoviridae

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

Poxviridae 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

Figure 24.2

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

Smallpox 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

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, tumorlike 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

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 Genital warts are associated with an increased risk of cancer

Epidemiology and Pathogenesis of Papillomavirus Infections
Transmitted via direct contact and via fomites autoinoculation Viruses that cause genital warts invade the skin and mucous membranes during sexual intercourse Genital warts are a common sexually transmitted disease

Diagnosis, Treatment, and Prevention
Usually based on observation of the papillomas 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 Treatment of cancers involves radiation and chemical therapy

Prevention of most types of warts is difficult Genital warts can be prevented by abstinence and perhaps safe sex

HPV vaccine Advisory committee on immunization practices (ACIP) recommended the HPV vaccine recommended for girls/women 9-26 yrs old before sexual contact recommended at years of age vaccine (Gardasil) protects against 4 HPV strains (HPV 6, 11, 16, and 18)

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

Adenoviridae 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

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

Herpesviridae Herpesviruses include various genera
Simplexvirus, Varicellovirus, Lymphocryptovirus, Cytomegalovirus, Roseolovirus 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 HHV2 = HSV2 HHV3 = VZV HHV4 = EBV HHV5 = CMV HHV6 = roseola infantum (major cause) HHV7 = roseola infantum (minor cause) HHV8 = KS

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

Figure 24.5

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 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

Figure 24.10

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

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 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

Cytomegalovirus 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

Cytomegalovirus 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 CMV causes infectious mononucleosis (second to EBV)

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

Other Herpesvirus Infections
Human herpesvirus 8 (HHV-8) Associated with Kaposi’s sarcoma, a cancer seen in AIDS patients The virus is not found in cancer-free patients or in normal tissues of victims

RNA Viruses 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

Poliovirus Enterovirus (RNA) Three serotypes: 1, 2, 3
Minimal immunity between serotypes Rapidly inactivated by heat, formaldehyde, chlorine, ultraviolet light Most poliovirus infections are asymptomatic

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

Poliomyelitis—United States, 1950-2007
Inactivated vaccine Live oral vaccine Last indigenous case

Comparison of Polio Vaccines
Table 25.2

Polio Vaccination Recommendations
Exclusive use of IPV recommended in 2000 OPV no longer routinely available in the United States

Schedules that Include Both IPV and OPV
Only IPV is available in the United States Schedule begun with OPV should be completed with IPV Any combination of 4 doses of IPV and OPV by 5 years constitutes a complete series

Polio Vaccine Adverse Reactions
Rare local reactions (IPV) No serious reactions to IPV have been documented Paralytic poliomyelitis (OPV)

Hepatitis A Epidemic jaundice described by Hippocrates
Differentiated from hepatitis B in 1940s Serologic tests developed in 1970s Vaccines licensed in 1995 and 1996

Hepatitis A Virus Picornavirus (RNA) Humans are only natural host
Stable at low pH Inactivated by high temperature (185°F or higher), formalin, chlorine

Hepatitis A Pathogenesis
Fecal oral entry Viral replication in the liver Virus present in blood and feces days after infection Virus excretion may continue for up to 3 weeks after onset of symptoms

Hepatitis A - United States, 1966-2007
Vaccine Licensed Year

Hepatitis A Vaccines Inactivated whole virus vaccines
Pediatric and adult formulations Pediatric formulations vaccines approved for persons 12 months through 18 years Adult formulations approved for persons 19 years and older

Hepatitis A Postexposure Prophylaxis
For healthy persons 12 months through 40 years of age: single-antigen hepatitis A vaccine should be administered as soon as possible after exposure For persons older than 40 years: immune globulin is preferred vaccine can be used if IG cannot be obtained MMWR 2007;56(No.41):1080-4

Rhinovirus Cause most cases of the common cold
Infections are limited to the upper respiratory tract A single virus is often sufficient to cause a cold The virus can be spread through aerosols, via fomites, or via hand-to-hand contact

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
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

Common Symptoms % of patients

Introduction to the Norwalk Virus
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. Occur frequently at institutional settings, ex Schools, nursing homes. Restaurants, dorms, cruise ships. Common source exposure. Raw shellfish, oysters – common. Australia, august 1996 Louisiana, December 1996 Florida, January 1995 Northeaster Florida/Louisiana, November 1993 Crowded quarters and poor hygiene contribute to its spread.

History Virus first identified in Norwalk, Ohio, 1973.
Noted to commonly be a problem on cruise ships. Associated with contaminated food or water supplies.

Infection Noroviruses found in stool and vomit of infected.
Very contagious – infection via eating contaminated food, contact with sick individual or contaminated surfaces. Very infectios – few virus particles needed to start large outbreak. Primarily fecal-oral. Vomit – airborne particles. Capable of covering large radius.

Symptoms Acute gastroenteritis.
Illness begins suddenly, from 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. Stomach flu, winter vomiting disease. Nausea, vomiting, stomach cramping, fever, chills, headache, muscle aches, tiredness,

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

Measles 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

Measles Highly contagious viral illness First described in 7th century
Near universal infection of childhood in prevaccination era Common and often fatal in developing areas

Measles Virus Paramyxovirus (RNA)
Hemagglutinin important surface antigen One antigenic type Rapidly inactivated by heat and light

Measles Pathogenesis 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

Measles Clinical Features
Incubation period days Prodrome Stepwise increase in fever to 103°F or higher Cough, coryza, conjunctivitis Koplik spots (rash on mucous membranes) Coryza = Head cold

Measles Clinical Features
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 Diarrhea Otitis media Pneumonia Encephalitis Hospitalization Death Percent reported 8 7 6 0.1 18 0.2 Based on surveillance data

Measles Laboratory Diagnosis
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
Vaccine Licensed

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

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 Only influenza and gonorrhea were more frequent among military personnel.

Mumps Virus Paramyxovirus RNA virus One antigenic type
Rapidly inactivated by chemical agents, heat, and ultraviolet light

Mumps Pathogenesis Respiratory transmission of virus
Replication in nasopharynx and regional lymph nodes Viremia days after exposure with spread to tissues Multiple tissues infected during viremia

Mumps Complications CNS involvement 15% of clinical cases Orchitis
Pancreatitis Deafness Death 15% of clinical cases 20%-50% in post- pubertal males 2%-5% 1/20,000 Average 1 per year (1980 – 1999)

Mumps—United States, 1980-2007 Year
Resurgence in involved primarily states that did not have school entry requirements for mumps. Year

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

What Is Bronchiolitis? 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 Slide 4 Bronchiolitis is an acute inflammation of the lower airways. It is characterised by wheeze and is defined as the first episode of acute wheezing in a child aged less than 1 year.1,2 Bronchiolitis results from a viral infection of the lower respiratory tract.1 RSV is the main causative agent recovered from young children with pneumonia and bronchiolitis, and may be responsible for up to 90% of cases of bronchiolitis in young children.3 Hall CB, McCarthy CA. In: Principles and Practice of Infectious Diseases 2000: ; Panitch HB et al. Clin Chest Med 1993;14: 115

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

Influenza 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 18-72 HR INCUBATION SHEDDING
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

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

Guillian-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
RNA virus immune response no longer protects fully sporadic outbreaks, limited epidemics

Figure 25.39

ANTIGENIC SHIFT “new” HA or NA proteins
pre-existing antibodies do not protect may get pandemics

Figure 25.39

Influenza epidemiology
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 B each year choose which variant of each subtype is the best to use for optimal protection

VACCINE 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

SUPPORTIVE TREATMENT REST, LIQUIDS, ANTI-FEBRILE AGENTS (NO ASPIRIN FOR AGES 6MTHS-18YRS) BE AWARE OF COMPLICATIONS AND TREAT APPROPRIATELY

Enveloped, Unsegmented Negative ssRNA Viruses
Includes the Paramyxoviridae, Rhabdoviridae, and Filoviridae families

Enveloped, Unsegmented Negative ssRNA Viruses
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 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

Rabies Rabies virus is the causative agent
Classical zoonotic disease of mammals Primary reservoir of rabies in urban areas is the dog

Rabies 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

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

Vaccination of domestic dogs and cats can help control rabies Little can be done to eliminate rabies in wild animals

Source: Centers for Disease Control and Prevention, November 2010
Map of terrestrial rabies reservoirs in the United States during Raccoon rabies virus variant is present in the eastern United States, Skunk rabies in the Central United States and California, Fox rabies in Texas, Arizona, and Alaska, and Mongoose rabies in Puerto Rico. Source: Centers for Disease Control and Prevention, November 2010

Hemorrhagic Fevers 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

Hemorrhagic Fevers 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.

History 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. 1994: Cote d’ Ivory- only one case here: a scientist conducted an autopsy on a wild chimpanzee. He fell ill, but did not die.

Strains Summary 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.

Transmission 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.

Symptomology 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.

Coagulpathy 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.”

Reservoirs 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.

Treatment 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
Barrier Nursing Techniques are employed to prevent further infection. Screens are placed around the patient’s bed. 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.

Cures/Vaccines 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

Rotavirus Pathogenesis
Entry through mouth Replication in epithelium of small intestine Replication outside intestine and viremia uncommon Infection leads to isotonic diarrhea

Rotavirus Immunity Antibody against VP7 and VP4 probably important for protection First infection usually does not lead to permanent immunity Reinfection can occur at any age Subsequent infections generally less severe

Rotavirus Clinical Features
Short incubation period (usually less than 48 hours) First infection after age 3 months generally most severe May be asymptomatic or result in severe dehydrating diarrhea with fever and vomiting Gastrointestinal symptoms generally resolve in 3 to 7 days

Rotavirus Complications
Severe diarrhea Dehydration Electrolyte imbalance Metabolic acidosis Immunodeficient children may have more severe or persistent disease

Risk Groups for Rotavirus Diarrhea
Groups with increased exposure to virus Children in child care centers Children in hospital wards (nosocomial rotavirus) Caretakers, parents of these children Children, adults with immuno- deficiency related diseases (e.g. SCID, HIV, bone marrow transplant)

Enveloped, Positive ssRNA Viruses
Includes the Togaviridae, Flaviviridae, and Coronaviridae families Togaviridae and Flaviviridae Enveloped, icosahedral, +ssRNA viruses Designated arboviruses because they are often transmitted by arthropods Coronaviridae Enveloped, helical, +ssRNA viruses

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

Rubella 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

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

Rubella Pathogenesis 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

Rubella Clinical Features
Incubation period 14 days (range days) Prodrome of low-grade fever Maculopapular rash days after exposure Lymphadenopathy in second week

Epidemic Rubella – United States, 1964-1965
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

Congenital Rubella Syndrome
Deafness Cataracts Heart defects Microcephaly Mental retardation Bone alterations Liver and spleen damage

Rubella Laboratory Diagnosis
Isolation of rubella virus from clinical specimen (e.g., nasopharynx, urine) Positive serologic test for rubella IgM antibody Significant rise in rubella IgG by any standard serologic assay (e.g., enzyme immunoassay)

Rubella and CRS in the United States
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 - United States, 1980-2007
Year

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

Enveloped, Segmented Negative ssRNA Viruses
Includes the Orthomyxoviridae, Bunyaviridae, and Arenaviridae families Orthomyxoviridae Flu viruses Bunyaviridae, and Arenaviridae Include hundreds of viruses that normally infect animals but can be transmitted to humans

Family Bunyaviridae 5 genera, 250 species Genus Human disease
Bunyavirus LaCrosse encephalitis, others Phlebovirus Rift Valley fever, sandfly fever Nairovirus Crimean-Congo hemorrhagic fever Tospovirus Plant virus, no known human disease Hantavirus Hemorrhagic fever with renal syndrome Hantavirus pulmonary syndrome

Diseases of Bunyaviruses
Most bunyaviruses are zoonotic pathogens Usually transmitted to humans by biting arthropods Infections result with an initial viremia spreading the virus to target organs

Diseases of Bunyaviruses
Symptoms are usually mild Hantviruses are the exception Transmitted to humans via inhalation of virions in dried deer-mouse urine or feces American strains can cause a rapid, severe, and often fatal pneumonia called hantavirus pulmonary syndrome

Hantavirus Outbreak in the US
HPS was first described in the United States in May 1993 during the investigation of a cluster of cases of acute adult respiratory distress in the Four Corners region. HPS was found to be caused by a previously unknown hantavirus, Sin Nombre, detected in deer mice. Sin Nombre caused approximately 200 confirmed cases of HPS during the outbreak, that led to a 50% mortality rate.

Hantavirus Genus Hantavirus Similarities Hantavirus Differences
RNA viruses Lipid membrane Tri-segmented genome Hantavirus Differences Hantavirus transmitted through aerosolized rodent urine, feces and saliva. Others genera transmitted through arthropod vectors.

Epidemiology and Rodent Hosts
Each strain of hantavirus has a specific rodent host Hantavirus species appear to have co-evolved with host rodent species Rodents carrying hantavirus are asymptomatic

Transmission of Hantaviruses
Chronically infected rodent Horizontal transmission of infection by intraspecific aggressive behavior Virus also present in throat swab and feces Virus is present in aerosolized excreta, particularly urine Secondary aerosols, mucous membrane contact, and skin breaches are also sources of infection Courtesy of CDC

Hantavirus Pulmonary Syndrome
Countries with reported cases of HPS (no of cases) Canada (36) Countries with no reported cases of HPS United States (335) Panama (31) Brazil (168) Bolivia (20) Paraguay (74) Uruguay (23) Chile (273) Argentina (404)

Hantavirus and Host Cells
Virus replication typically halts host macromolecule synthesis Hantavirus replication does not affect host cell’s natural functions Hantavirus release does not require host cell lysis Hantavirus is able to establish a persistent infection in rodent host cells

Hantavirus Infection Pathogenesis
Binding of Hantavirus glycoproteins integrin causes disruption of vascular integrity Capillaries become more permeable Arteriole vasoconstriction and vasodilation are disrupted Binding to platelet receptors affects clotting and platelet function

Immune Reaction Immune system activated against Hantavirus epitopes
Virus epitopes expressed on surface of host cells triggers cytotoxic T-cell attack on host tissues Symptoms are consistent with inflammatory response

Laboratory Diagnosis of Hantavirus
Hantavirus is difficult to culture, so morphological identification is difficult RT-PCR using primers for conserved genome regions allows confirmation of infection PCR product can be sequenced and compared to known viral sequence database for species identification

Clinical Presentation of Hantavirus Infection
Three different clinical manifestations of hantavirus infection caused by different viral strains Hemorrhagic fever with renal syndrome (HFRS) Found in Europe and Asia Nephropathia Epidemica (NE) Found in Europe Hantavirus pulmonary syndrome (HPS) Found in north and south America

HPS 1993 four corners outbreak
Cases found in almost all of the Americas ~50% fatality

Stages of Hantavirus Pulmonary Syndrome (HPS)
Incubation (4-30 days) Febrile phase Cardiopulmonary phase Diuretic phase Convalescent phase

Febrile Phase 3-5 days Fever, myalgia, malaise
Other symptoms: headache, dizziness, anorexia, nausea, vomiting, and diarrhea.

Cardiopulmonary Phase
4-24 hours Presentation and rapid progression of shock and pulmonary edema (4-24h non-productive cough and tachypnea (shortness of breath) Decreased blood volume fromleakage of high protein fluid from blood to lung Death within hours due to hypoxia (lack of oxygen) and/or myocardial failure

Diuretic Phase Several days to several weeks Beginning of recovery
Rapid clearance of pulmonary edema Resolution of fever and shock Anorexia, fatigue due to dehydration

Convalescent Phase Up to 2 months
Results in chronic decreased small-airway volume and diminished alveolar diffusing capacity

Clinical Testing for HPS
Many lab tests and radiographs appear normal Serological tests more effective ELISA IgM capture assay, using either SNV, Laguna Negra, or Andes antigens are used in all countries that have previously detected cases Immunofluorescent test for the presence of antibodies Blood analysis also may find thrombocytopenia with platelet count less than 150,000 mm in 98% of cases

Problems Diagnosing HPS
Symptoms often confused with influenza Common signs of upper respiratory disease such as sore throat, sinusitis, and ear pain not usually present Abdominal pain often misinterpreted as appendicitis Many doctors outside endemic regions fail to recognize or have sufficient testing

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