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