Diseases

1. Diseases Influenza Mono Viral Hepatitis Human Immunodeficiency Virus Rabies Scrapie Creutzfeldt-Jakob (CJD) Chronic wasting disease (CWD) Bovine spongiform encephalopathy (BSE) Tuberculosis (TB) Chicken pox & Shingles Ebola

2. Pathogens • Disease causing agents that have the ability to make you sick or even cause death • They are found in the air and food and on nearly every object or person who you come in contact with

3. Uncontrollable Risk Factors • Heredity • Chromosomal traits and family history • Aging • Vulnerability increases with age • Environmental Conditions • Unsanitary conditions, drugs, chemicals, and pollutants • Organism Resistance • Some pathogens are resistant to our body’s defenses and/or medical treatments

4. Controllable Risk Factors • Stress • Nutrition • Physical fitness level • Sleep • Drug use • Hygiene • High-risk behaviors

5. Routes of Pathogen Transmission • Direct Contact • Touching, kissing, sexual relations • Indirect Contact • Touching an object that an infected person has had contact with • Airborne Contact • Breathing in air that carries a pathogen • Food-borne infection • Eating something that is contaminated by microorganisms

6. Routes of Pathogen Transmission • Animal-borne pathogens • Animals can spread diseases through bites, feces, or by carrying infected insects into living areas • Water-borne diseases • Transmitted from drinking water, from foods washed or sprayed with contaminated water, or from wading or swimming in contaminated streams, lakes or reservoirs • Perinatally • Mothers can transmit diseases to an infant in the womb or as the baby passes through the vagina during birth

7. Bacteria • Single-celled organisms • There are several thousands of species, but only about 100 cause diseases in humans • Most of the time it is not the bacteria that is causing the diseases, but it is the toxins that are produced by the bacteria • They can be seen under a standard microscope

8. Bacterial Diseases • Staphylococcal Infections • These bacteria are normally on our skin at all times and usually do not cause problems • When a cut or break in the skin occurs, the bacteria may enter and cause an infection • Acne, boils, styes (eyelid infections), wounds are common staph infections

9. Bacterial Diseases • Streptococcal Infections • Causes strep throat and scarlet fever • Pneumonia • One form is caused by a bacterial infection with the following symptoms: chronic cough, chest pain, chills, high fever, fluid accumulation and eventual respiratory failure

10. Bacterial Diseases • Legionnaire’s Disease • A water-borne disease with symptoms similar to those of pneumonia • Tuberculosis (TB) • An airborne disease where bacteria infiltrate the lungs and cause a chronic inflammatory reaction • Symptoms include coughing, weight loss, fever and spitting up blood

11. Viruses • Minute (very tiny) parasitic microbes that live inside another cell • Over 150 viruses are known to cause diseases in humans • Viral diseases are hard to treat because many can withstand heat, chemicals and large doses of radiation with little effect on their structure

12. Viral Diseases • The Common Cold • There may be over 200 different viruses responsible • Carried into the nose and throat most of the time • Stress, allergies, and menstrual cycles appear to increase susceptibility

13. Viral Diseases • Influenza (flu) • Symptoms include aches and pains, nausea, diarrhea, fever, and cold like ailments • In healthy people, it is usually not serious • However, when combined with other disorders, among the elderly, those with respiratory or heart disease, children under 5 the flu can be very serious

14. Viral Diseases • Mononucleosis (mono or the kissing disease) • Symptoms include sore throat, fever, headache, nausea, chills, weakness or tiredness, lymph nodes may swell, jaundice (yellow skin), spleen enlargement, aching joints, and body rashes may occur • May be transmitted through body fluids but does not appear to be easily contracted through normal, everyday contact

15. Viral Diseases • Hepatitis • Causes inflammation of the liver • Symptoms include fever, headache, nausea, loss of appetite, skin rashes, pain in the upper right abdomen, dark yellow urine, and jaundice

16. Viral Diseases • Hepatitis A (HAV) • Contracted from eating food or drinking water contaminated with human feces • Hepatitis B (HBV) • Spread through body fluids, usually during unprotected sex • Can lead to liver disease or liver cancer • Hepatitis C (HBC) • Some cases can be traced from people who share needles, blood transfusions or organ transplants • Usually causes chronic infections and if not treated may cause cirrhosis of the liver, liver cancer, or liver failure

17. VI. A. Influenza • Properties • Member of the Orthomyxovirus family • Enveloped RNA virus • Two envelope proteins • Hemagglutinin and Neuraminidase • Segmented RNA • 8 segments; packaged into helical nucleocapsids • Antigenic variation & genetic exchange lead to the appearance of new strains; requires use of different vaccine combinations each year

18. VI. A. Influenza • Symptoms & Complications of Influenza • Respiratory Tract Symptoms • Fever • Neurological Complications: • Guillain-Barré Syndrome • Reye’s Syndrome

19. VI. B. Diseases Caused by the Herpes Family • Properties of the Herpes Virus Family • Large, enveloped DNA viruses • Icosahedral capsids • DNA replicates in the nucleus of host cells • Cells may become permanently infected • Host chromosomes may be altered • Herpes infections associated with certain cancers

20. VI. B. Diseases Caused by the Herpes Family • Herpes Simplex • Two major strains • Type I: Oral Herpes • Type II: Genital Herpes • Skin lesions form at site of the infection • Virus travels along sensory neurons to ganglia, where it remains • During times of stress or weakened immunity, virus may travel along same neurons to re-infect the initial skin sites

21. VI. B. Diseases Caused by the Herpes Family • Chicken pox & Shingles • Cause: Varicella-zoster virus • Chicken pox symptoms • Shingles symptoms • Treatment • Chicken pox vaccine • Connection to Reye’s syndrome

22. VI. D. Human Immunodeficiency Virus • Viral Properties • A retrovirus • An enveloped RNA virus that replicates through a DNA intermediate • The DNA intermediate is synthesized by reverse transcriptase: an enzyme that makes a DNA molecule using an RNA template • The DNA intermediate is spliced into host chromosomes, making the infection permanent

23. VI. D. Human Immunodeficiency Virus • Viral Properties (cont.) • Host cells for HIV: CD4+ cells • Helper T (T-4) lymphocytes • Macrophages • Damage to the helper T cell population cripples the immune system of the host

24. VI. D. Human Immunodeficiency Virus • Transmission • Contact with infected body fluids • Blood, blood products, semen, vaginal secretions, breast milk

25. VI. D. Human Immunodeficiency Virus • What is the difference between HIV & AIDS? • HIV: the Human Immunodeficiency Virus • The cause of AIDS • Also known as: HTLV-III and LAV • Two known types: HIV-1 and HIV-2 • AIDS: Acquired Immune Deficiency Syndrome • Catastrophic immune system failure caused by HIV infection • Symptoms & cases are usually defined by the CDC case surveillance definition

26. VI. D. Human Immunodeficiency Virus • CDC Case Surveillance Definition for AIDS • Based on: • Clinical Symptoms: Categories A, B, C • Helper T-4 lymphocyte count: Categories 1, 2, 3 • Category A • Asymptomatic HIV infection • Persistent Generalized L ymphadenopathy • Acute HIV infection

27. VI. D. Human Immunodeficiency Virus • CDC Case Surveillance Definition for AIDS (cont.) • Category B • Symptomatic HIV infection with constitutive illness & certain opportunistic infections • Often an early indication that AIDS is developing • *Category C • Symptomatic HIV infection with opportunistic infections listed in the CDC surveillance case definition

28. VI. D. Human Immunodeficiency Virus • CDC Case Surveillance Definition for AIDS (cont.) • Category 1 • T-4 count greater than 400 per microliter of blood • Category 2 • T-4 count between 400 and 200 per microliter of blood • *Category 3 • T-4 count less than 200 per microliter of blood

29. VI. D. Human Immunodeficiency Virus • CDC Case Surveillance Definition for AIDS (cont.) • *These categories (C and 3) meet the CDC surveillance definition to be included among the AIDS cases • Many HIV-infected individuals show no symptoms, yet are capable of transmitting the virus

30. VI. D. Human Immunodeficiency Virus • Symptoms & Secondary Infections Associated with AIDS • Acute Infection • Fever, lymph node swelling, aches, fatigue, “flu-like” or “mono-like” symptoms • Persistent Generalized Lymphadenopathy • Lymph node swelling for greater than 6 months in two or more body areas (excluding the groin) • Often an early manifestation that AIDS has developed

31. VI. D. Human Immunodeficiency Virus • Symptoms & Secondary Infections Associated with AIDS (cont.) • Constitutive Illness • Weight loss, persistent fever, diarrhea • Cancers • Kaposi’s sarcoma • Certain lymphomas

32. VI. D. Human Immunodeficiency Virus • Symptoms & Secondary Infections Associated with AIDS (cont.) • Bacterial Secondary Infections • Mycobacterium • Listeria • Salmonella • Mycoplasma • many others

33. VI. D. Human Immunodeficiency Virus • Symptoms & Secondary Infections Associated with AIDS (cont.) • Fungal Secondary Infections • Candida and others • Protozoan Secondary Infections • Toxoplasma gondii • Cryptosporidium • Pneumocystis carinii

34. VI. D. Human Immunodeficiency Virus • Symptoms & Secondary Infections Associated with AIDS (cont.) • Viral Secondary Infections • Herpes simplex • Cytomegalovirus • Many others • Treatments • Inhibitors of DNA replication • Protease Inhibitors

35. Rhabdoviruses • Features • Bullet-shaped (75 x 180 nm) • Enveloped • Single stranded RNA genome, 12 kb • Many viruses with broad host ranges • Classification • Family Rhabdoviridae • Genus Lyssavirus (including Rabies virus) • Vertebrates • Invertebrates • Plants • Genus Vesiculovirus (Vesicular stomatitis-like viruses)

36. Rabies Virus • Rabies virus replication • Spike protein mediates attachment (nicotinic acetylcholine receptor) • Viral RNA polymerase transcribes a monocistronic mRNA • Five polypeptides are encoded by the genome • N • L (polymerase) • P (polymerase) • M • G • The N assembles with the polymerase and RNA in progeny virus (spiral configuration) • Virus exits by budding • G protrudes from plasma membrane • M binds to inner PM leaflet

37. Rabies Virus • Animal susceptibility • All warm-blooded animals can be infected with varying susceptibility • High - wolves, coyotes, foxes, dogs • Intermediate - skunks, raccoons, bats • Low - opossums • Virus occurs in saliva, nervous system, urine, lymph, milk • Recovery is rare and only occurs in bats; fatal in nearly all others • Vampire bats can transmit virus for months

38. Rabies Virus • Pathogenesis • Requires several weeks for infection to become apparent • Transmission through bite or scratch from infected animal • Replication in muscle and connective tissues at site of inoculation • Enters peripheral nervous system at neuromuscular junctions • Spreads up the peripheral nerves to the central nervous system • Encephalitis • Virus grows to high titers in the salivary glands • Rabies patients must be restrained • Negri bodies appear in neuron cell bodies • Clinical spectrum • Prodrome - nausea, headaches, fever, sore throat, photophobia • Acute neurologic phase - apprehension, nervousness, hallucinations, behavioral anomalies, salivation, perspiration, hydrophobia, photophobia • Coma - seizures and death (99+%) Negri bodies

39. Rabies Virus • One survival using novel medical treatment • NEJM. 2005. 352:2508-2514 • 15 year old Jeanna Giese bitten by a bat • Presented with clinical rabies after one month • Treatment • Induced coma • Administered high doses of ketamine to suppress brain activity • Required mechanical ventilation • Administered heparin • Administered ribavirin, an antiviral, to protect the heart from rabies-induced cardiomyopathy • Days 8-10 showed improvement in cardiovascular and neurological functions • By day 23 she could sit up in bed, but neurological manifestations persisted • Required prolonged physical therapy, but is continuing to recover • This treatment failed for a Texas boy

40. Rabies Virus • Laboratory diagnosis • PCR • Serology (IFA) • Animal control • Rabid or suspected rabid animals are killed and examined by histopathology for Negri bodies and viral antigen • Vaccination of pets is required by law in most states • Immunity and protection • Vaccines • First one developed by Pasteur by using spinal cords from infected dogs • Today’s principal vaccine is the human diploid cell vaccine (HDCV) made in the WI-38 fibroblast cell line • Virus is inactivated by βPL • Post-exposure prophylaxis • One dose of hyperimmune antiserum • Five immunizations over 28 days

41. Rabies Virus • Epidemiology • Enzootic in wild and domesticated animals • In the U.S., edible vaccines are dispersed to control wild animal rabies • More than 200 people die from rabies in China each month • Reservoirs might be bats • But the slow-growing nature of rabies virus also contributes to its persistence in nature

42. Prion Diseases • Proteinacious infectious agents • Diseases are transmissible spongiform encephalopathies (TSEs) • There are also inherited spongiform encephalopathies • Human • Creutzfeldt-Jakob Disease - sporatic • New Variant CJD - from beef (“mad cow disease”) • Kuru - ritualistic cannibalism (consuming brains of infected dead) • Fatal familial insomnia • Animal • Bovine spongiform encephalopathy (“mad cow” disease) • Scrapie - sheep • Chronic wasting disease - deer, elk, moose

43. Transmissible Spongiform Encephalopathy Prion Diseases

44. TSEs • Group of diseases caused by same infectious agent • Causes same pathology in respective hosts • Microscopic sponge like holes in brain • Clinical signs are all neurological in nature Center for Food Security and Public Health Iowa State University - 2004

45. Human TSE’s • Kuru • Creutzfeldt-Jakob disease (CJD) • Familial, sporadic, iatrogenic • A variant of CJD (vCJD) • Gerstmann-Straussler-Scheinker syndrome (GSS) • Fatal familial insomnia (FFI) Center for Food Security and Public Health Iowa State University - 2004

46. Animal TSE’s • Bovine Spongiform Encephalopathy (BSE, “mad cow disease”) • Scrapie (sheep) • Chronic wasting disease (CWD) (elk and deer) • Mink Spongiform Encephalopathy (TME) • Feline Spongiform Encephalopathy (FSE) Center for Food Security and Public Health Iowa State University - 2004

47. The Organism

48. Prion • Smaller than smallest known virus • Not yet completely characterized • Most widely accepted theory • Prion = Proteinaceous infectious particle • Normal Protein • PrPC (C for cellular) • Glycoprotein normally found at cell surface inserted in plasma membrane Center for Food Security and Public Health Iowa State University - 2004

49. Secondary structure dominated by alpha helices Easily soluble Easily digested by proteases Encoded by PRNP gene (in humans) Located on human chromosome 20 Normal protein Center for Food Security and Public Health Iowa State University - 2004

50. PrPSc (Sc for scrapie) Same amino acid sequence and primary structure as normal protein Secondary structure dominated by beta conformation When PrPSc contacts PrPC Converts it to the abnormal form Abnormal Protein Center for Food Security and Public Health Iowa State University - 2004