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 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 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 Some 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

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.

Tertiary Structures of Prion proteins
Figure 13.21

Virus Diseases Prion Diseases RNA Viruses DNA Viruses Mad Cow Disease
Creutzfeldt–Jakob disease Kuru DNA Viruses Poxviridae: Smallpox Herpesviridae: Cold sores, chicken pox, mononucleosis Hepadnoviridae: Hepatitis B Papillomaviridae: Warts Adenoviridae: Common cold, pink eye RNA Viruses Picornaviridae: Polio, Hepatitis A, common cold Coronaviridae: Common cold Calicivirus: Stomach flu Flaviviridae: Hepatitis C; West Nile Retroviridae: AIDS Togaviridae: German Measles Paramyxovirus: Measles, mumps Orthomyxovirus: Influenza Rhabdoviridae: Rabies Filoviridae: Hemorrhagic Fever Reoviridae: Stomach flu

Prion Diseases Cattle Humans Kuru
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

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 (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.

Fore Tribe of Papua, New Guinea

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, Hepadnoviridae, Papillomaviridae, and Adenoviridae

DNA Viruses Three are enveloped Three are non-enveloped
There are currently 21 families of viruses known to cause disease in humans. There are six ds DNA families: Three are enveloped Poxviridae, Herpesviridae, and Hepadnaviridae Three are non-enveloped Papillomaviridae, Adenoviridae, Polyomaviridae (the latter is not covered here) There is one ss DNA family that infects humans: They are non-enveloped Parvoviridae (not covered here)

Creutzfeldt–Jakob disease Kuru DNA Viruses Poxviridae: Smallpox Herpesviridae: Cold sores, chicken pox, mononucleosis Hepadnoviridae: Hepatitis B Papillomaviridae: Warts Adenoviridae: Common cold, pink eye RNA Viruses Picornaviridae: Polio, Hepatitis A, common cold Coronaviridae: Common cold Calicivirus: Stomach flu Flaviviridae: Hepatitis C; West Nile Retroviridae:AIDS Togaviridae: German Measles Paramyxovirus: Measles, mumps Orthomyxovirus: Influenza Rhabdoviridae: Rabies Filoviridae: Hemorrhagic Fever Reoviridae: Stomach flu

DNA Viruses Poxviridae Herpesviridae Hepadnoviridae Papillomaviridae
Smallpox Herpesviridae Cold sores, chicken pox, mononucleosis Hepadnoviridae Hepatitis B Papillomaviridae Warts 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

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 severe 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, 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 usually little other damage Cowpox was used by Edward Jenner to immunize individuals against smallpox

Rescued kitten infected girl with rare virus
A teenager in the Netherlands who rescued a drowning kitten from a ditch developed a large, blackened open wound on her wrist, which took multiple doctors several weeks to find its rare cause.

The kitten that the girl rescued was sick and died the following day, and the 17-year-old developed a red wound on her wrist that blistered before turning black. She also developed painful red bumps on her arm, spanning from the wound on her wrist up to her armpit.

The doctors got in touch with a virologist whose lab was equipped to run tests for cowpox. A few days later, lab results proved the cowpox virus was, indeed, the culprit. The girl had been treated by different doctors for about 13 days by then.

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 (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)

Herpes simplex virus type 1 (HSV-1)

Herpes simplex virus type 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

Diagnosis, Treatment, and Prevention
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: Chicken Pox
Chicken pox 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

Chicken Pox

What is Chicken Pox? Chicken pox is a common illness that causes an itchy rash and red spots or blisters (pox) all over the body. The blisters are small and sit on an area of red skin that can be anywhere from the size of a pencil eraser to the size of a dime.

Causes Chickenpox is caused by a virus called varicella zoster. (VZV) is a type of herpes virus that causes two types of diseases, chickenpox and shingles. It’s an airborne virus that can spread easily . You can get it from an infected person who sneezes, coughs, or by sharing food or drinks. You can also get it if you touch the fluid from a chickenpox blister. The infected person is highly contagious for 1-2 days before the rash appears and continue to be contagious through the first 4-5 days or until all the blisters have crusted over. Late winter and early spring is the most common time that the virus spreads.

Symptoms It usually takes 14 to 16 days to get the symptoms of chickenpox after you have been around someone with the virus. This is called the incubation period. The first symptoms of chickenpox are often fever, headache, and sore throat. Other symptoms include: Being Tired Loss of appetite Flu like symptoms Rash (First appears on the face and trunk, and then spreads throughout the body) Itchy blistering (There are typically itchy blisters). More Severe/Unusual Symptoms Skin around spots/blisters become painful and red Breathing difficulties Chest pain Scars Pneumonia Brain damage Death

Symptoms The illness is highly contagious and can be spread by direct contact or through the air by sneezing or coughing. Also, someone can get it by coming in contact with fluid from chickenpox blisters. For that reason, children with chickenpox need to be kept out of school or day care for about a week or more until all blisters have dried and crusted over. The illness causes an itchy rash that usually forms between 200 and 500 blisters over the entire body, headaches, coughing, and fussiness. So even if the illness is mild, it still means five to 10 days of being uncomfortable.

Who Is Affected? Common illness among kids in the United States, particularly those under age 12. You are at risk for chickenpox if you have never had the illness and have not had the chickenpox vaccine. Living with someone who has chickenpox. It is usually a mild disease, however it can be serious, especially in young infants and adults.

Treatments A doctor may prescribe or advice on how to reduce symptoms of itchiness and discomfort, and also on how to prevent the infection from spreading to other people. Treatment depend on a person’s age, heath, and severity. Home remedies: Tylenol or Ibuprofen to reduce fever and discomfort. Over the counter antihistamines may help reduce itching. Oatmeal baths and soothing lotions (calamine, or aveeno). Antiviral medicines sometimes are given to shorten the length of the illness. Healthy teens and adults with varicella usually have more severe symptoms than children and are at a higher risk for complications, still most home remedies should work.

Possible Complications
Risk complications are greater with pregnant women and newborns up to 4 weeks of age, as well as those with weakened immune systems (cancer patients undergoing chemotherapy, or have a chronic condition such as lupus or rheumatoid arthritis). In rare cases the blisters become infected with bacteria. If the skin around the spots and blisters become red and tender, most likely they have become infected. According to the NHS (National Health Service) between 5% to 14% of all adults with chickenpox develop respiratory complications, such as pneumonia. The risk is significantly greater for adults smokers. Some other complications from chickenpox may include meningitis, and blood poisoning. Even though complications are possible, most patients who have them make a full recovery.

Epidemiology and Pathogenesis of VZV Infections: Shingles
Latent virus can reactivate later in life, producing a rash known as shingles The rash is characteristic for its localization along a dermatome - dorsal roots from the spine

Figure 24.10

Shingles Also known as Herpes Zoster Painful blistering skin rash

Causes Caused by the Varicella- Zoster virus also known as the virus that causes chicken pox After you get chicken pox the virus remains dormant. Reasons it may become active again are a low immune system, older in age 60 and above, or if you got chicken pox before the age of 1.

Shingles

Signs and Symptoms Red Patches on the skin followed by small blisters
The blisters break, forming small sores that begin to dry and form crusts. The crusts fall off in 2 to 3 weeks. The rash usually involves a narrow area from the spine around to the front of the belly area or chest. The rash may involve the face, eyes, mouth, and ears.

Signs and Symptoms also include
Abdominal pain Fever and chills General sick feeling Genital sores Headache Joint pain Swollen glands (lymph nodes)

Treatment Physician may prescribe an antiviral drug such as Acyclovir, Famciclovir, and Valacyclovir. Strong anti-inflammatory medicines called corticosteroids, such as prednisone, may be used to reduce swelling and pain

Vaccination CDC recommends two doses of chickenpox vaccine for children, adolescents, and adults. Two doses of the vaccine are about 98% effective at preventing chickenpox. Children should receive two doses of the vaccine—the first dose at 12 through 15 months old and a second dose at 4 through 6 years old. When you get vaccinated, you protect yourself and others in your community. This is especially important for people who cannot get vaccinated, such as those with weakened immune systems or pregnant women. Some people who are vaccinated against chickenpox may still get the disease. However, it is usually milder with fewer blisters and little or no fever.

Are Children Required to Get a Chickenpox Vaccination?
Most states require that children entering child care, school and even colleges and universities, show evidence of immunity to chickenpox either by having had the illness or evidence of receiving the chickenpox vaccine.

Monitoring the Impact of Varicella Vaccination
Chickenpox used to be very common in the United States. In the early 1990s, an average of 4 million people got varicella, 10,500 to 13,000 were hospitalized (range, 8,000 to 18,000), and 100 to 150 died each year. In the 1990s, the highest rate of varicella was reported in preschool-aged children. Chickenpox vaccine became available in the United States in In 2010, 90% of children 19 to 35 months old in the United States had received one dose of varicella vaccine, varying from 72% to 97% by state and city. Among adolescents 13 to 17 years of age without a prior history of disease, 90% had received 1 dose of varicella vaccine, and 58% had received 2 doses of the vaccine. Each year, more than 3.5 million cases of varicella, 9,000 hospitalizations, and 100 deaths are prevented by varicella vaccination in the United States. Varicella incidence in 26 states, which had adequate and consistent reporting to the National Notifiable Disease Surveillance System (NNDSS), declined by 45% from 2000 to 2005 with an additional 77% decline from 2006 to 2010 after the second dose of varicella vaccine was recommended. Overall, varicella declined 82% from 2000 to 2010. National hospitalization rates for varicella declined overall by 71% during 2000 to 2006 compared with rates from 1988 to In people younger than 20 years of age, hospitalization rates declined by approximately 95%. Varicella deaths declined by 98.5% in children and adolescents less than 20 years of age during 2008 to 2009 compared with 1990 to Deaths declined by 96% in adults less than 50 years of age and by 49% in adults 50 years of age or older. Varicella incidence among HIV-infected children declined 63% during compared to Varicella vaccination provides indirect benefits to people who are not eligible for vaccination. Varicella incidence among infants, a group not eligible for varicella vaccination, declined by 90% from 1995 to 2008.

People at High Risk for Complications
Immunocompromised Persons Immunocompromised persons who get varicella are at risk of developing visceral dissemination (VZV infection of internal organs) leading to pneumonia, hepatitis, encephalitis, and disseminated intravascular coagulopathy. They can have an atypical varicella rash with more lesions, and they can be sick longer than immunocompetent persons who get varicella. The lesions may continue to erupt for as long as 10 days, may appear on the palms and soles, and may be hemorrhagic. People with HIV or AIDS Children with HIV infection tend to have atypical rash with new crops of lesions presenting for weeks or months. HIV-infected children may develop chronic infection in which new lesions appear for more than one month. The lesions may initially be typical maculopapular vesicular lesions but can later develop into non-healing ulcers that become necrotic, crusted, and hyperkeratotic. This is more likely to occur in HIV-infected children with low CD4 counts. Some studies have found that VZV dissemination to the visceral organs is less common in children with HIV than in other immunocompromised patients with VZV infection. The rate of complications may also be lower in HIV-infected children on antiretroviral therapy or HIV-infected persons with higher CD4 counts at the time of varicella infection. Retinitis can occur among HIV-infected children and adolescents. Most adults, including those who are HIV-positive have already had varicella disease and are VZV seropositive. As a result, varicella is relatively uncommon among HIV-infected adults.

People at High Risk for Complications
Pregnant Women Pregnant women who get varicella are at risk for serious complications; they are at increased risk for developing pneumonia, and in some cases, may die as a result of varicella. If a pregnant woman gets varicella in her 1st or early 2nd trimester, her baby has a small risk (0.4 – 2.0 percent) of being born with congenital varicella syndrome. The baby may have scarring on the skin, abnormalities in limbs, brain, and eyes, and low birth weight. If a woman develops varicella rash from 5 days before to 2 days after delivery, the newborn will be at risk for neonatal varicella. In the absence of treatment, up to 30% of these newborns may develop severe neonatal varicella infection.

Possible Side Effects of Chickenpox Vaccine
Getting chickenpox vaccine is much safer than getting the disease. Most people who get the vaccine do not have any problems with it. But, as with any vaccine, there is a very small chance of having a side effect. Serious side effects to the chickenpox vaccine are very rare. They are usually more likely to occur after the first dose than after the second one.

Possible reactions include: Soreness, redness, or swelling where the shot was given Fever Mild rash or several small bumps after vaccination. If you get chickenpox rash after vaccination, you can spread the disease to others. But, this is very rare. If you have chickenpox rash, you should stay away from people with weakened immune systems. Seizure (jerking and staring spell) that may be caused by fever. Seizures after chickenpox vaccination may or may not be related to chickenpox vaccine. Serious side effects from chickenpox vaccine are extremely rare. They may include severe brain reactions and low blood count. These side effects happen so rarely that experts cannot tell whether they are caused by chickenpox vaccine or not.

Possible reactions after ProQuad® (or MMRV) vaccination Children who get the first dose of ProQuad® vaccine at 12 to 23 months old may have a higher chance of a seizure caused by fever. This is in comparison to children who get the measles, mumps, and rubella vaccine and the chickenpox vaccine separately during a doctor visit. But, these seizures are not common. They may be scary for parents, but they are not harmful to children.

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 CMV causes infectious mononucleosis (second to EBV)

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

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) 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

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

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, 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.

Hepatitis B 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.

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 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

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

Pinpoint bleeding on debridement

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 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 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

Single-stranded RNA viruses
RNA viruses are either double stranded or single stranded. The single stranded RNA viruses are subclassified according to the sense or polarity of their RNA: they are called positive-sense RNA viruses or negative-sense RNA viruses. Positive-sense viral RNA is similar to mRNA and thus can be immediately translated by the host cell. Negative-sense viral RNA is complementary to mRNA and thus must be converted to positive-sense RNA by an RNA polymerase before translation.

RNA Viruses There are seven positive ss RNA families:
Three are non enveloped Picornaviridae, Caliciviridae, and Astroviridae (latter one not covered) Four are enveloped Coronoviridae, Flaviviridae, Retroviridae, and Togaviridae There are six negative ss RNA families: All are enveloped Paramyxoviridae, Orthomyxoviridae, Rhabdoviridae, Filoviridae, Arenaviridae, and Bunyaviridae (latter two not covered) There is one ds RNA family Reoviridae

Creutzfeldt–Jakob disease Kuru DNA Viruses Poxviridae: Smallpox Herpesviridae: Cold sores, chicken pox, mononucleosis Hepadnoviridae: Hepatitis B Papillomaviridae: Warts Adenoviridae: Common cold, pink eye RNA Viruses Picornaviridae: Polio, Hepatitis A, common cold Calicivirus: Stomach flu Coronaviridae: Common cold Flaviviridae: Hepatitis C; West Nile Retroviridae: AIDS Togaviridae: German Measles Paramyxovirus: Measles, mumps Orthomyxovirus: Influenza Rhabdoviridae: Rabies Filoviridae: Hemorrhagic Fever Reoviridae: Stomach flu

RNA Viruses Paramyxovirus Orthomyxovirus Rhabdoviridae Filoviridae
Picornaviridae Polio, Hepatitis A, common cold Calicivirus Stomach flu Coronaviridae Common cold Flaviviridae West Nile Hepatitis C Retroviridae AIDS Togaviridae German Measles Paramyxovirus Measles, mumps Orthomyxovirus Influenza Rhabdoviridae Rabies Filoviridae Hemorrhagic Fever Reoviridae Stomach flu

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

RNA virus in the news Yosemite officials say 1,700 visitors risk rare rodent disease

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

Hepatitis A This is a virus you get when you or a food worker doesn’t wash the hands after going to the bathroom, and then you eat. It CAN also be sexually transmitted through oral/anal contact, but it is not primarily considered as a STD.

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 Cough and sneeze into your elbow. Wash hands often.

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

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, New 'vomiting virus' strain behind recent US outbreaks,

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

Flaviviridae West Nile Virus Hepacivirus Hepatitis C

West Nile Virus Mosquito-borne virus first identified in the West Nile area of the East African nation of Uganda in 1937. Birds are the most common animal infected. Approximately 80% of West Nile virus infections in humans are subclinical, which cause no symptoms. In the cases where symptoms do occur —termed West Nile fever in cases without neurological disease—the time from infection to the appearance of symptoms (incubation period) is typically between 2 and 15 days. Symptoms may include fever, headaches, fatigue, muscle pain.

West Nile Virus Less than 1% of the cases are severe and result in neurological disease when the central nervous system is affected by encephalitis (brain infection).

BIG BEAR LAKE: West Nile Virus found in squirrel
A dead gray tree squirrel found July 9, 2013 at Big Bear Lake has tested positive for West Nile virus. Most people get infected with the virus by the bite of an infected mosquito that fed on an infected bird. About 1 in 5 people develop a symptom such as a fever.

Hepatitis C

Hepatitis C This is the form you get PRIMARILY from infected blood.
It is very serious and can lead to chronic hepatitis, liver cancer, and death. It CAN be transmitted sexually, but it is not PRIMARILY known as a STD.

Jury awards $41.7M to student disabled on field trip to China
A jury awarded $41.7 million to a woman who sued her prestigious boarding school after contracting a Tick-borne encephalitis virus on a school trip to China that left her unable to speak and brain damaged. Munn, of New York City, was a ninth-grader when she joined a school-supervised trip to China during the summer of 2007, according to her lawsuit. The then-15-year-old suffered insect bites that led to tick-borne encephalitis, her attorneys said. The school failed to ensure that the students take any precautions against ticks and allowed them to walk through a densely wooded area known to be a risk area for tick-borne encephalitis and other tick- and insect-transmitted illnesses, her attorneys said.

Retroviridae A retrovirus only has mRNA therefore is an obligate intracellular parasite. Once inside the host cell cytoplasm the virus uses its own reverse transcriptase enzyme to produce DNA from its mRNA. This is the reverse of the usual replication pattern, so it is named a retro (backwards) virus. The host cell then treats the viral DNA as part of its own genome, translating and transcribing the viral genes along with the cell's own genes, producing the proteins required to assemble new copies of the virus. It is difficult to detect the virus until it has infected the host.

Retroviridae Human Immunodeficiency Virus (HIV)
Causes acquired immunodeficiency syndrome (AIDS). The HIV virus infects Helper T-Cells, and the AIDS disease causes progressive failure of the immune system, which allows life- threatening opportunistic infections and cancers to thrive. Infection with HIV occurs by the transfer of blood, semen, vaginal fluid, pre-ejaculate, or breast milk.

AIDS During the initial infection, a person may experience a brief period of influenza-like illness. This is typically followed by a prolonged period without symptoms. As the illness progresses, it interferes more and more with the immune system, making the person much more likely to get infections, including opportunistic infections and tumors that do not usually affect people who have working immune systems.

AIDS HIV is transmitted primarily via unprotected sexual intercourse (including anal and even oral sex), contaminated blood transfusions, hypodermic needles, and from mother to child during pregnancy, delivery, or breastfeeding. Some bodily fluids, such as saliva and tears, do not transmit HIV. Prevention of HIV infection, primarily through safe sex and needle-exchange programs, is a key strategy to control the spread of the disease. There is no cure or vaccine; however, antiretroviral treatment can slow the course of the disease and may lead to a near-normal life expectancy. While antiretroviral treatment reduces the risk of death and complications from the disease, these medications are expensive and may be associated with side effects.

Difference between HIV + and having AIDS
If you have a positive AIDS test, you are considered to be HIV positive. Then you get a blood test. If your helper T- Cell count (CD4) is below 200 mm3, the diagnosis is AIDS. If the cell count is higher, you do not have AIDS yet, but you are still HIV positive. You need to have blood tests periodically. It takes up to six months for an HIV test to show positive after exposure.

AIDS Genetic research indicates that HIV originated in west-central Africa during the early twentieth century. AIDS was first recognized by the Centers for Disease Control and Prevention (CDC) in 1981 and its cause—HIV infection—was identified in the early part of the decade. Since its discovery, AIDS has caused an estimated 36 million deaths (as of 2012). As of 2012, approximately 35.3 million people are living with HIV globally. AIDS is considered a pandemic—a disease outbreak which is present over a large area and is actively spreading.

HIV is being used as a possible cure for cancer
used-to-cure-cancer-leukemia.html

Enveloped, Positive ssRNA Viruses
Togaviridae Rubivirus (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

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

Paramyxoviridae Orthomyxovirus Rhabdoviridae Filoviridae
Measles and Mumps Orthomyxovirus Influenza Rhabdoviridae Rabies Filoviridae Ebola virus

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 (head cold), 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 As many as one in 20 children with measles gets pneumonia and about one in 1,000 develop encephalitis. For every 1,000 children who get measles, one or two will die, according to the U.S. Centers for Disease Control and Prevention. The measles virus is easily spread when an infected person coughs or sneezes.

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 (MMR) 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, especially parotid salivary glands

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

Respiratory Syncytial Virus
Respiratory Syncytial Virus (RSV) may be responsible for up to 90% of bronchiolitis cases in young children Bronchiolitis is acute inflammation of the airways, characterised by wheeze. A syncytium is a multinucleate cell which can result from multiple cell fusions 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

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 Usually caused by excess aspirin consumption in children, especially during viral infections. liver - fatty deposits brain - edema vomiting, lethargy, coma risk factors youth certain viral infections (influenza, chicken pox) aspirin

NON-PULMONARY COMPLICATIONS OF INFLUENZA
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 –especially in Asia Kills >20,000 per year in the US normally

Swine Flu

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 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
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 97% of cases of human rabies is from the bite of an infected dog. That is why the government passed a law to mandate that all pet dogs have a rabies vaccination. Most human deaths from rabies is from the bite of a bat, which goes unnoticed and therefore is untreated.

Rabies Any warm blooded animal can get rabies if bitten by an infected animal. All rabies-infected animals will die within 30 days of being bitten. The only exception are the few animals that are asymptomatic carriers of rabies: Bats Skunks Raccoons Foxes

Rabies It usually takes about 30 days for symptoms to show after a bite from an infected animal (the virus slowly travels towards the brain), but sometimes symptoms begin as early as 4 days. Treatment must begin within 10 days after exposure. Once symptoms occur, treatment does not work and the disease is always fatal in 2-10 days. Patient with rabies, 1959

Rabies (“Madness”) Early-stage symptoms of rabies are malaise, headache and fever, progressing to acute pain, violent movements, uncontrolled excitement, depression, and hydrophobia. Finally, the patient may experience periods of mania and lethargy, eventually leading to coma. The primary cause of death is usually respiratory insufficiency. Frothing at the mouth is caused by paralysis of the tracheal muscles, making it hard to swallow.

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

Rabies All human cases of rabies were fatal until a vaccine was developed in 1885 by Louis Pasteur and Émile Roux. Their original vaccine was harvested from infected rabbits, from which the virus in the nerve tissue was weakened by allowing it to dry for five to ten days. They injected the vaccine into 50 dogs in June, and 10 days later injected the dogs with blood from a rabid dog. They then had to wait 30 days to make sure the vaccine worked.

Rabies However, on July 6, a poor peasant woman spent her life savings on a train ticket to transport her 9 year old son 200 miles to Paris to see Dr. Pasteur. He had been bitten by a rabid dog and she had heard of Pasteur’s work on the smallpox vaccine. Since Pasteur was a chemist and not a medical doctor, he had to convince the medical doctor to administer the vaccine. Pasteur told him he had tested the vaccine on 50 dogs, but he did not tell him the 30 day period had not elapsed yet.

Rabies Not all people bitten by a rabid animal will get rabies, so no one could be sure that the boy even had the virus. The vaccination regimen was to give 2 shots a day, starting with a very weakened virus, and increasing the virulence of the organism each day. By the 10th day, the shots would contain the fully virulent live rabies organism. If the person did not have rabies, they will now!

Rabies They then injected the vaccine into a boy with rabies. They gave one injection on each side of the abdomen, into the peritoneal cavity. These injections were repeated daily for 10 days, and on the last day, they gave him the live rabies virus. It was the first time a human ever survived rabies. Therefore, they continued this painful treatment until the 1990’s since they did not know what else to do!

First rabies cure Nine year old Joseph Meister had been bitten by a dog that had rabies. The boy recovered after receiving the vaccine from Pasteur. When he grew up he became a caretaker at the Pasteur Institute.

Rabies Modern treatment is just one injection of human rabies immunoglobulin (HRIG) into the deltoid muscle. This is 100% effective if given early. Awakening to find a bat in the room, or finding a bat in the room of a previously unattended child or mentally disabled or intoxicated person, is regarded as an indication for this post-exposure prophylaxis. Prevention 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 garcinia 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 There is an oral vaccine called "Rotarix“.
It is given to babies at 2 months of age and the second at 4 months of age. If the infant has not completed the vaccination by 5 months of age, it is ineffective.

Randy Travis in critical condition with viral cardiomyopathy
July 9, 2013 the singer's health deteriorated rapidly over the past several days after he developed what he thought was a cold. The Mayo Clinic website describes cardiomyopathy as a disease that weakens and enlarges the heart muscle, making it harder for the heart to pump blood and carry it to the rest of the body. It can lead to heart failure. Treatments range from medications and surgically implanted devices to heart transplants.

Viral cardiomyopathy Viral cardiomyopathy occurs when viral infections cause myocarditis with a resulting thickening of the myocardium and dilation of the ventricules. These viruses include Coxsackie B and adenovirus, echoviruses, influenza H1Ni, Epstein-Barr virus, rubella (German measles virus), varicella (chickenpox virus), mumps, measles, parvoviruses, yellow fever, dengue fever, polio, rabies and the viruses that cause hepatitis A and C.

Creutzfeldt–Jakob disease Kuru DNA Viruses Poxviridae: Smallpox Herpesviridae: Cold sores, chicken pox, mononucleosis Hepadnoviridae: Hepatitis B Papillomaviridae: Warts Adenoviridae: Common cold, pink eye RNA Viruses Picornaviridae: Polio, Hepatitis A, common cold Coronaviridae: Common cold Calicivirus: Stomach flu Flaviviridae: Hepatitis C; West Nile Retroviridae: AIDS Togaviridae: German Measles Paramyxovirus: Measles, mumps Orthomyxovirus: Influenza Rhabdoviridae: Rabies Filoviridae: Hemorrhagic Fever Reoviridae: Stomach flu

Love Story I will seek and find you. I shall take you to bed and have my way with you. I will make you ache, shake & sweat until you moan & groan. I will make you beg for mercy, beg for me to stop. I will exhaust you to the point that you will be relieved when I'm finished with you. And, when I am finished, you will be weak for days. All my love, The Flu Now get your mind out of the gutter and go get your Flu shot!

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