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37_lecture

Course: BIO 326R, Spring 2011
School: University of Texas
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37 Human Chapter Diseases Caused by Viruses and Prions 1 Airborne Diseases when human is source, airborne viruses are propelled from respiratory tract by coughing, sneezing, or vocalizing 2 Chickenpox (Varicella) and Shingles (Herpes Zoster) DNA virus, member of Herpesviridae acquired by droplet inhalation into humans serve as reservoir and source respiratory system chickenpox results from initial infection vaccine prevents or shortens illness 3 Figure 37.1 4 Chickenpox (Varicella) and Shingles (Herpes Zoster)... shingles (herpes zoster; postherpetic neuralgia) reactivated form of chickenpox treatment virus resides in cranial and sensory neurons reactivation virus migrates down neuron supportive; acyclovir and others 5 Figure 37.2 6 Influenza (Flu) respiratory system disease caused by influenza virus RNA virus; acquired by inhalation or ingestion of respiratory secretions classified into subtypes based on hemagglutinin (HA) and neuraminidase (NA), membrane surface glycoproteins HA and NA function in viral attachment and virulence 16 HA and 9 NA antigenic forms are known; they recombine to produce HA/NA influenza subtypes 7 Influenza (Flu)... an important feature of the influenza viruses is the frequency with which changes in antigenicity occur antigenic drift due to accumulation of mutations in a strain within a geographic area antigenic shift due to reassortment of genomes when two different strains of flu viruses (from humans and animals) infect the same cell and are incorporated into a single new capsid (bird flu, swine flu) 8 Influenza (Flu)... clinical manifestations chills, fever, headache, malaise, and general muscular aches and pains recovery usually within 3 to 7 days often leads to secondary infections by bacteria treatment, prevention, and control rapid immunologic tests symptomatic/supportive therapy inactivated virus vaccine 9 Measles (Rubeola) measles rash caused by measles virus (RNA virus) enters body through respiratory tract subacute sclerosing panencephalitis rare progressive degeneration of central nervous system caused by measles virus treatment, prevention, and control symptomatic/supportive therapy attenuated measles vaccine MMR vaccine (measles, mumps, rubella) 10 Figure 37.4 11 Mumps... caused by mumps virus, RNA virus clinical manifestations treatment, prevention, and control develop 1618 days after infection fever, and swelling and tenderness of salivary glands complications include meningitis and orchitis (inflammation of testis) symptomatic/supportive therapy live, attenuated vaccine (MMR) 12 Respiratory Syncytial Virus (RSV) considered to be the most dangerous respiratory infections in young children RSV is negative strand RNA virus spread by hand contact and respiratory causes formation of syncytia (fused cells) secretions 13 RSV Infection... clinical manifestations acute onset of fever, cough, rhinitis, and nasal congestion often progresses quickly to severe bronchitis and viral pneumonia treatment, prevention, and control rapid immunologic tests inhaled ribavirin and RSVimmune globulin isolation, protective clothing, and hand washing (virus is readily inactivated by soap and disinfectants) 14 Rubella (German Measles) enveloped RNA virus mild rash of three days acquired from respiratory droplets congenital rubella syndrome disastrous disease in the first trimester of pregnancy can lead to fetal death, premature delivery, or congenital defects 15 Figure 37.5 16 Severe Acute Respiratory Syndrome (SARS) highly contagious viral disease caused by the SARS associate corona virus (SARSCoV) transmitted by droplet spread onset of sudden, severe illness in otherwise healthy individual dry cough develops after a few days and most will develop pneumonia if not detected early, disease can be fatal no specific treatment is currently approved 17 Smallpox (Variola) caused by variola virus transmitted by aerosol or contact large, brickshaped complex virus linear dsDNA humans are the only natural host once one of the most prevalent of all diseases case fatality rate of 2050% no longer in human populations remains a potential bioterrorism agent 18 Figure 37.7 19 Clinical Forms of Smallpox Variola major Variola minor most common and more severe form of disease extensive rash and higher fever 33% fatality rate less common form and less severe fatality rates of 1% or less both forms are usually transmitted by direct and fairly prolonged facetoface contact but has been reported to be spread through air in enclosed settings 20 Eradication of Smallpox 1977 last case from a natural infection occurred in Somalia why eradication was possible disease has obvious clinical features humans are only hosts and reservoirs there are no asymptomatic carriers short infectivity period (34 weeks) 21 ArthropodBorne Diseases arboviruses viruses transmitted by bloodsucking arthropods from one vertebrate host to another multiply in tissues of vector without producing disease vector acquires a lifelong infection 22 Clinical Syndromes undifferentiated fevers, with or without rash encephalitis hemorrhagic fevers inflammation of the brain fatality rate is usually high frequently severe and fatal e.g., Ebola virus and Marburg virus supportive treatment, no vaccines available 23 RNA virus causing disease transmitted to humans by Equine Encephalitis mosquitoes a spectrum of symptoms which can ultimately result in death genetically distinct strains found in different geographic locations e.g., Western equine encephalitis (WEE) and Eastern equine encephalitis (EEE) strains no vaccine available 24 West Nile Fever (Encephalitis) caused by a flavivirus, RNA virus appeared in New York in 1999 causing human and animal deaths by 2006 found in all continental U.S. states, infecting humans or animals transmitted to humans by Culex spp., mosquitoes that feed on sparrows and crows 25 West Nile Fever... human to human spread has occurred through blood and organ donation only one antigen type exists and immunity is presumed to be permanent clinical manifestations treatment, prevention, and control fever, lymphadenopathy, rash >1/100 patients develop serious complications (e.g., encephalitis) serology tests supportive treatment mosquito control measures 26 Direct Contact Diseases transmission of disease through direct personal contact touching, kissing, sexual contact, contact with body fluids, contact with open wounds many diseases including AIDS 27 Acquired Immune Deficiency Syndrome (AIDS) caused by human immunodeficiency virus (HIV); RNA virus family Retroviridae theories on origin of disease HIV1 evolved from chimp virus only group M HIV1 is widespread in U.S. HIV2 is widespread in Africa 28 HIV Transmission when infected blood, semen, or vaginal secretions come in contact with uninfected person's broken skin or mucous membranes 29 HIV Life Cycle... virion has viral protein spike, gp120 attaches to CD4 cells (T helper cells and other cells) and coreceptors CCR5 and CXCR4 RNA virus carries reverse transcriptase into host cell reverse transcribed into dsDNA, which integrates into human genome as provirus 30 Figure 37.8 31 HIV Life Cycle... integrates into host cell's DNA as a provirus can remain latent asymptomatic can direct synthesis of viral RNA synthesis of new viral particles new virion are assembled and released through budding and eventual lysis 32 Course of Disease some patients rapidly develop clinical AIDS; die within 23 years some patients remain relatively healthy for at least 10 years post infection in majority of patients HIV infection progresses to AIDS in 810 years T helper cell count reduces and opportunistic infections begin 33 CDC Classification System for Stages of HIVRelated Conditions acute 28 weeks after infection most experience brief illness called acute retroviral syndrome rapid multiplication and dissemination of virus throughout body stimulation of immune response may last from 6 months to 10 or more years effects on immune functions may occur 34 asymptomatic (latent) CDC Classification System for Stages of HIVRelated Conditions... chronic symptomatic formerly called AIDSrelated complex can last for months to years viral replication continues numbers of CD4 + cells in blood significantly decrease results in patients developing a variety of illnesses often caused by opportunistic pathogens and AIDS related cancers 35 Figure 37.11 36 CDC Classification System for Stages of HIVRelated Conditions... AIDS fourth and last stage definition of AIDS immune system no longer able to defend against virus all HIVinfected individuals who have fewer than 200 CD4+ T cells/microliter of blood or a CD4+ cell percentage of lymphocytes of less than 14 37 Diagnosis viral isolation and culture assays for reverse transcriptase activity or viral antigens most commonly done by detection of specific antiHIV antibodies in the blood routine screening tests use ELISA assays which have many false positive results which are retested using Western blot technique most sensitive test uses polymerase chain reaction 38 Treatment no cure for AIDS treatment directed at reducing viral load, disease symptoms, and treating disease and malignancies most successful treatment involves a combination of drugs 39 Antivirals Used nucleoside reverse transcriptase inhibitors, e.g., AZT nonnucleoside reverse transcriptase inhibitors, e.g., delavirdine protease inhibitors, e.g., indinavir fusion inhibitors (FIs) prevent entry of HIV into cells, e.g., enfuvirtide 40 Prevention and Control achieved primarily though education barrier protection from blood and body fluids not sharing intravenous needs or syringes continued screening of blood and blood products 41 Vaccine not available but ongoing research problems with development of vaccine envelope proteins of virus continually change their antigenic properties 42 Cold Sores fever blisters (herpes labialis) caused by herpes simplex virus type 1 (HSV1) usually, but also can be herpes simplex virus type 2 (HSV2) HSV infect epithelium at oral sites active infection latent infections explosive multiplication of virus virus moves to trigeminal ganglion and is nondetectable unless reactivated 43 Cold Sores... clinical manifestations characteristic blister at site of inoculation gingivostomatitis lips, mouth, and gums herpetic keratitis cornea lifetime latency develops, with periodic reactivation in times of stress treatment, prevention, and control diagnosis by ELISA, direct fluorescent antibody screening of tissue or PCR acyclovir and other antivirals no vaccine, education important 44 Figure 37.13 45 Common Cold caused by many different rhinoviruses (ssRNA viruses); also by coronaviruses and parainfluenza viruses seasonal peaks and transmitted by: excretion of virus in nasal secretion airborne transmission by droplets contaminated hands or fomites symptomatic/supportive therapy 46 Cytomegalovirus Inclusion Disease worldwide distribution caused by human cytomegalovirus (HCMV) dsDNA virus, Herpesviridae HCMV can infect any cell of the body causes formation of intranuclear inclusion bodies and cytoplasmic inclusions 47 HCMV Inclusion Disease... virus shed in semen and cervical solutions also can be transmitted by blood transfusions and organ transplants usually asymptomatic infection can be serious in immunocompromised individuals leading cause of congenital viral disease symptoms often resemble mononucleosis treatment, prevention, and control antiviral agents used for highrisk patients avoiding close personal contact with actively infected individual 48 Genital Herpes usually caused by herpes simplex type 2 very common sexually transmitted disease and to infant during vaginal delivery (congenital or neonatal herpes) active and latent disease with reactivations clinical manifestations fever, burning sensation, genital soreness, and blisters in infected area blisters heal spontaneously, but virus remains latent and is periodically reactivated can be treated with antiviral drugs (e.g., acyclovir) 49 Genital Herpes... congenital (neonatal) herpes usually HSV2 one of the most lifethreatening of all infections in newborns ~1,5002,200 babies/year in U.S. can result in neurologic involvement and blindness Caesarian section recommended 50 Human Herpesvirus 6 Infections HHV6 tropism is wide, including CD8+, CD4+, natural killer, and epithelial cells proviral DNA in human chromosomes probably transmitted in saliva clinical manifestations shortlived disease of infants high fever for 3 to 4 days, followed by macular rash pneumonitis in immunocompromised individuals implicated in chronic fatigue syndrome, lymphadenitis, and multiple sclerosis in immunocompetent adults no treatment or prevention measures 51 Human Parvovirus B19 Infections significant human pathogen infection thought to be by respiratory route mild symptoms (fever, headaches, chills, malaise) in most normal adults erythema infectiosum (fifth disease) in children joint disease in some adults aplastic crisis in individuals with sicklecell disease or autoimmune hemolytic anemia pure red cell aplasia in immunocompromised individuals treatment, prevention, and control passive immunization with antiB19 antibodies infection usually followed by lifelong immunity hand washing is best prevention for disease 52 Mononucleosis (Infectious) caused by EpsteinBarr virus (EBV) spread by mouthtomouth contact herpes virus infects B cells also associated with Burkitt's lymphoma and nasopharyngeal carcinoma 53 Mononucleosis... clinical manifestations treatment, prevention, and control enlarged lymph nodes and spleen, sore throat, headache, nausea, general weakness and tiredness, and mild fever selflimited disease, lasting 1 to 6 weeks rapid diagnostic tests symptomatic/supportive therapy 54 Figure 37.17 55 Viral Hepatitis hepatitis inflammation of liver caused by 11 different viruses 2 herpesviruses--EpsteinBarr virus (EBV) and cytomegalovirus (CMV) 9 hepatotropic viruses EBV and CMV cause mild, selfresolving disease no permanent hepatic damage signs and symptoms include fatigue, nausea, and malaise 56 Table 37.2 57 Hepatitis B (Serum Hepatitis) Hepatitis B virus (HBV) dsDNA virus Dane particle is infectious virion transmitted through body fluids and intravenous equipment can pass the placenta and breast milk ~1.25 million chronically infected in U.S., 200 million worldwide 58 Hepatitis B (Serum Hepatitis)... clinical signs most cases asymptomatic generalized symptoms occurs after 13 month incubation period virus infects liver hepatic cells causing liver damage yellow appearance (jaundice) results from bilirubin accumulation chronic infection can cause development of primary liver cancer (2nd only to tobacco as known cause of cancer) 59 Hepatitis B (Serum Hepatitis) prevention and control passive immunotherapy within 7 days of exposure excluding contact with contaminated materials vaccination of highrisk groups 018 year olds contacts of carriers healthcare professionals 60 Hepatitis C Virus (HCV) RNA virus in Flaviridae family multiple genotypes transmission via contaminated blood, fecal oral route, also spread from mother to fetus, and through organ transplants epidemic with more than 1 million new cases/yr in U.S. chronic infection common leading cause of liver transplant in U.S. treatment, prevention, and control ELISA test for antibodies and PCR for nucleic acid combination therapy of Ribavirin and recombinant interferonalpha 61 Hepatitis Delta Virus (HDV) Delta agent, RNA virus discovered in 1977 dependent on HBV to provide the envelope protein (HbsAG) for HDV RNA genome transmission by body fluids causes severe acute and chronic hepatitis in HBV infected treatment, prevention, and control serological tests for antiHDV antibodies no satisfactory treatment 62 Warts verrucae horny projections on skin associated with human papillomaviruses DNA virus, Papillomaviridae family more than 100 different strains infect epithelium and mucus membranes benign epithelial tumors and cancers 63 Warts four major types direct contact and autoinoculation treatment plantar warts verrucae vulgaris flat or plane warts anogenital condylomata (genital warts) physical destruction, topical application of drug podophyllum, or injection of IFN 64 Genital Warts (Anogenital very common sexually transmitted HPV Condylomata) 16 month incubation period warts, usually multiple, found on external genitalia, in vagina, or cervix or in rectum most infections clear spontaneously specific types of HPV cause at least 90% of cervical cancers vaccine available against HPV 16 and 18 which are responsible for causing ~80% of cancers 65 Diseases transmitted by fecaloral route 66 Gastroenteritis (Viral) acute viral gastroenteritis caused by four major groups of viruses inflammation of stomach or intestines important disease of infants and children leading cause of childhood death in developing countries probably spread by fecaloral route 67 Gastroenteritis (Viral)... Rotavirus, adenovirus, and astrovirus ~510 million deaths/year worldwide rotavirus live oral vaccines Norovirus ~23 million cases of acute gastroenteritis/yr usually selflimited disease symptomatic/supportive therapy 68 Hepatitis A Virus infectious hepatitis spread by fecaloral contamination of food, drink, or shellfish clinical manifestations usually mild intestinal infection anorexia, general malaise, nausea, diarrhea, fever, and chills occasionally viremia occurs leading to liver infection jaundice treatment, prevention, and control immunodiagnostic tests for HAV antibodies simple hygienic measures, sanitary disposal of excreta, and killed HAV vaccine 69 Hepatitis E Virus implicated in many epidemics in developing countries transmission by fecal contaminated water similar to HAV course of disease ~15%25% fatality rates in pregnant women 70 Poliomyelitis polio (infantile paralysis) caused by poliovirus three subtypes with no cross immunity very stable in food and water multiplies in throat and intestinal mucosa 71 Polio... clinical manifestations usually asymptomatic or brief, mild illness fever, headache, sore throat, vomiting, loss of appetite viremia sometimes occurs sometimes persists and virus enters central nervous system causing paralytic polio prevented by immunization with live vaccine and killed vaccine 72 Zoonotic Diseases animal reservoirs for human viral infections RNA viruses, many are on Select Agents list as potential bioweapons Ebola and Marburg viruses Hantaviruses Lassa fever virus Nipah virus 73 Ebola and Marburg Hemorrhagic Fevers viral hemorrhagic fever (VHF) severe multisystem syndrome caused by many distinct viruses overall host vascular system is damaged leading to vascular leaking (hemorrhage) and dysfunction (coagulopathy) 74 Ebola Hemorrhagic Fever member of singlestranded, negative sense RNA family called the Filoviridae infection is severe and ~80% fatal no known carrier state; fruit bat may be reservoir transmission from direct contact with Ebola victim, body fluids or clinical samples internal hemorrhage supportive therapy but no specific treatment available 75 Marburg Hemorrhagic Fever genetically unique RNA virus in Filoviridae rare, severe disease that affects human and nonhuman primates indigenous to Africa definitive animal host not identified symptoms come on abruptly and become increasingly severe multiorgan dysfunction supportive therapy but no specific treatment available 76 Hantavirus Pulmonary Syndrome (HPS) transmitted to humans by inhalation of virus particles shed in urine, feces, or saliva of infected rodents potentially deadly for humans but do not cause disease in their reservoir (rodent) hosts supportive therapy but no specific treatment available 77 Rabies caused by different strains of rabies virus negative strand, bullet shaped, RNA virus highly neurotropic transmitted by: bites of infected animals aerosols in caves where bats roost contamination of scratches, abrasions, open wounds, or mucous membranes with saliva of infected animals fewer than 10 cases/yr in U.S. 78 Rabies... enters host cell and multiplies enters nervous system, spreads to spinal cord first specific symptoms (pain or paresthesia at wound) may occur rapidly progressive encephalitis develops as virus spreads through central nervous system then spreads through body along peripheral nerves, including salivary glands, where it is shed in saliva 79 Rabies... clinical manifestations begins 2 to 16 weeks after exposure pain or paresthesia at wound site, anxiety, irritability, depression, fatigue, loss of appetite, fever, and sensitivity to light and sound quickly progresses to paralysis death results from destruction of regions of the brain that regulate breathing 80 Rabies... diagnosis previously used microscopic observation of Negri bodies, masses of viruses or unassembled particles currently use direct immunofluorescent antibody (dIFA) of brain tissue, virus isolation, Negri body detection and a rapid rabies enzymemediated immunodiagnosis test 81 Rabies... treatment, prevention, and control numerous diagnostic tests, including rapid immunodiagnostic tests postexposure vaccination preexposure vaccination of individuals with high risk of exposure, dogs, and cats 82 Prion Diseases transmissible spongiform encephalopathies fatal neurogenerative disorders caused by prions remains clinically silent for months or years ends in profound disability or death diseases include Kuru, CreutzfeldtJacob (CJD) disease, and variant CJD, bovine spongiform encephalopathy (BSE) transmission medical procedures, genetic, foodborne 83 Prion Diseases... prions (protein infectious particles) consist of abnormally folded proteins (PrPsc) which can induce normal forms of protein PrPc to abnormally fold BSE agent survives gastrointestinal tract passage, and is neurotropic, both serve as source of agent 84 Prion Diseases dementia is primary symptom usually accompanied by motor dysfunction symptoms appear after prolonged incubation and last from months to years prior to death produce characteristic spongiform degeneration of brain and deposition of amyloid plaques share many characteristics with Alzheimer's disease 85 NewVariant CJD transmitted from cattle that have bovine spongiform encephalopathy (BSE) or mad cow disease evidence suggests that human vCJD can be acquired by eating meat products such as brain and spinal cord tissue from infected cattle 86

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