Pre-Lecture 1 The major virulence factor of Corynebacterium diphtheriae is A. B. C. D. E. Ability to multiply within macrophage Capsule Endotoxin Exotoxin Neurotoxin Physician Assistant Review Lippincott Williams and Wilkins 2001 2 A physician assistant student presents to the primary care office with a lesion on his foot. History reveals he walks barefoot in the shower at the local gym. The lesion on the bottom of the foot is flat and has grown inward. There is another lesion on the side of the foot that appears filiform. Which of the following is most likely the causative agent? A. B. C. D. E. Coronavirus Papilloma virus Poxvirus Rubella virus Togavirus Physician Assistant Review Lippincott Williams and Wilkins 2001 3 Where does the rash begin in cases of rubella? A. B. C. D. E. Back Chest Head/neck Inguinal region Wrist Physician Assistant Review Lippincott Williams and Wilkins 2001 4 A three year old, unknown to your clinic previously, presents and has a high fever, cough, coryza, conjunctivitis, and a rash. Koplik spots are noted on the buccal mucosa. The conjunctivae reveal a transverse line of inflammation along the eyelid margin (Stimson line). The rash is morbiliform, began on the head, and then spread over most of the body in a descending fashion within 18-20 hours. This clinical presentation is consistent with a diagnosis of A. B. C. D. E. Herpes Zoster Human Herpesvirus-6 Measles (Rubeola) Rubella (German, 3-Day Measles) Meningiococcal Physician Assistant Review Lippincott Williams and Wilkins 2001 5 www.khanacademy.org Under Biology—Review Physiology Role of Phagocytes in Innate or Nonspecific Immunity Types of immune responses: innate and adaptive B lymphocytes Professional Antigen Presenting Cells Helper T cells Cytotoxic T cells Review of B cells CD4 and CD8 T cells Inflammatory Response Review 6 To convert Fahrenheit temperatures into Celsius: Tc=(5/9)*(Tf-32) Begin by subtracting 32 from the Fahrenheit number. Divide the answer by 9. Then multiply that answer by 5. To convert Celsius temperatures into Fahrenheit: Tf=(9/5)*Tc+32 Begin by multiplying the Celsius temperature by 9. Divide the answer by 5. Now add 32. Review 7 Review Body’s Response to Infections Vaccination Related Infectious Diseases 8 To put things in perspective… Bacterial and viral diarrheas Bacterial pneumonias Tuberculosis Measles Malaria Hepatitis B Kill more people each year than all cancer and cardiovascular diseases combined Pertussis Tetanus Impact greatest in less developed countries 9 Complex of properties that allows an organism to establish infection and to cause disease or death Gain access to the body Avoid multiple host defenses Ex., Capsules prevent phagocytosis “Some killers have pretty nice capsules” S. pneumoniae, K. pneumoniae, H. influenza, P. aeurginosa, N. meningitidis, and the yeast C. neoformans Accommodate to growth in the human milieu Parasitize human resources Review 10 Mainly cause disease in hosts with impaired defenses Many are part of normal endogenous human or environmental microbial flora Take advantage of inadequate defenses to attack more violently and concertedly Review 11 Anatomic Barriers Skin Aerodynamic filtration system of upper airway Mucociliary blanket of airway Anatomy Review: Which cells produce mucous in respiratory tract? Goblet Cells Normal microbial flora Compete with outside organisms Review 12 Secretions Possess antimicrobial properties Nonspecific Lysozyme Specific Immunoglobulin A (IgA) Gastric Acid or bile Review 13 Binding molecule on an infecting organism with a receptor molecule on the host If host lacks a suitable receptor, the organism cannot attach Ex., Plasmodium vivax causes malaria Targets Duffy blood group determinants on the red blood cell surface Many persons, particularly blacks, lack these determinants and are not susceptible to infection Review 14 Can affect outcome of exposure In Utero Ex., CMV, rubella, parvovirus interfere with fetal development Maternal response minimal; while potential fetal harm Normally, IgG—generated from mom previous infection—passively crosses placenta and protects fetus Review: When does maternal IgG usually go away in child? About six months Children younger than 3 Diarrhea Adults Chickenpox causes great problems Elderly Fare more poorly with almost all infections than younger persons 15 Sexually transmitted infections Occupational exposure Wearing shoes Single most important factor in reducing soil transmitted nematodes Eating undercooked foods 16 Skin Burns or trauma Mucociliary apparatus Smoking or influenza Congenital absence of complement components C5 – C8 Prevents membrane attack complex to fully function Co-morbid diseases May interfere with neutrophil production or function 17 CDC Scheduled Childhood Vaccination Related IDs 18 Rotavirus Poliovirus Diphtheria Influenza Pertussis Measles Tetanus Mumps Haemophilus Rubella Pneumococcus Varicella Hepatitis A Meningococcal Hepatitis B Human Papilloma Virus 19 Most diarrhea of kids especially in winter! 20 Most common cause of severe diarrhea worldwide Dehydration and death if untreated 100 deaths in U.S. 1 million deaths worldwide Double-stranded RNA Oral to fecal route Peak age of infection is 6 months to 2 years Virtually all infected by age of 5 years Adults usually mildly affected Can be re-infected Subsequent infections usually less severe 21 Infects enterocytes of the upper small intestine Disrupts absorption of sugars, fats, and various ions Resulting osmotic load causes a net loss of fluid into the bowel lumen Produces diarrhea and dehydration Review: What other disease process causes an osmotic process? Hint: diuresis Diabetes mellitus Infected cells are shed from intestinal villi Regenerating epithelium initially lacks full absorptive capabilities 22 Largely confined to the duodenum and jejunum Shortening of the intestinal villi Mild infiltrate of neutrophils and lymphocytes 23 Lethargy Child will not focus on you or less responsive to words/touch Vomiting 2 to 3 days Fever Clinically defined as? Abdominal pain Profuse, watery diarrhea 5 to 8 days Without fluid replacement, diarrhea can produce fatal dehydration in young children Clinical presentation of dehydration? 24 http://www.articlediary.com/assets/rotavirus.jpg 25 Direct immune based assays (ELISA or latex agglutination) and PCR Fluid replacement Supportive BRAT diet Prevention Vaccination 26 Greek for “Leather” 27 Necrotizing upper respiratory tract infection Infection with Corynebacterium diphtheriae Aerobic, pleomorphic, gram-positive rod Humans are the only known reservoir Most asymptomatic carriers Spreads from person to person in respiratory droplets or oral secretions 28 Bacterium enters the pharynx and proliferates Often on the tonsils Produces exotoxin causes an inflammatory response Also inhibits protein synthesis Toxin is absorbed systemically and acts on tissues Heart, nerves, and kidney most susceptible 29 Characteristic lesions—Pseudomembranes Thick, gray, leathery membranes composed of sloughed epithelium, necrotic debris, neutrophils, fibrin, and bacteria that line affected respiratory passages Epithelial surface beneath the membranes is denuded, and the submucosa is acutely inflammed and hemorrhagic 30 http://www.vaccineinformation.org/photos/diphaap001.jpg http://ezproxy.butler.edu:4053/contents/image?imageKey=ID%2F11187&topicKey=ID%2 F8051&source=see_link&utdPopup=true 31 Fever Sore throat Malaise Cervical lymphadenopathy “Bull Neck” 32 http://www.vaccineinformation.org/photos/diphaap002.jpg 33 Cardiac and neural symptoms develop in minority of patients When heart affected, the myocardium displays fat droplets in the myocytes and focal necrosis Neural tissue—affected peripheral nerves show demyelination Cutaneous diphtheria Inoculation of the organism into a break in the skin and manifests as a pustule or ulcer Rarely leads to cardiac or neurologic complications 34 http://upload.wikimedia.org/wikipedia/commons/1/1b/A_diphtheria_skin_lesion_on_the_leg._PHIL_1941_lores.jpg 35 Mostly based on clinical presentation Definitive diagnosis Isolating C. diphtheriae from infected site Selective media needed for throat culture—routine methods cannot isolate organism Positive toxin production assay 36 Prompt administration of Antitoxin Antibiotics Isolation of patient/ hospitalization Manage complications Active immunity with DPT Immunity wanes over time Decennial booster doses are required to maintain protective antibody levels 37 AKA Whooping Cough 38 Bordetella pertussis Gram negative, pleomorphic coccobacilli Highly contagious Respiratory droplets Incubation period range 6 – 14 days Lasts 2 months Three phases Catarrhal -- 1 – 2 weeks Paroxysmal -- 2 – 4 weeks Convalescent -- 1 – 2 weeks 39 Most contagious during this time Rhinorrhea Conjunctival injection Lacrimation Varies mild to hacking night cough Low grade fever May resemble a simple URI at this stage 40 Episodes of cough increase in severity and frequency Forceful coughs during expiration are followed by a sudden massive inspiration producing a whoop http://www.whoopingcough.net/cough-child- muchwhooping.wav Facial petechiae and redness Cyanosis Posttussive vomiting Exhausting; appear apathetic 41 Paroxysmal coughing and vomiting decrease in frequency and severity Chronic cough may last for several months 42 Elevated white blood cell count with lymphocytosis Isolation of B. pertussis by culture of nasopharyngeal swab with Bordet-Gengou or other special medium 43 Antibiotic may shorten contagious period but is of little use during the paroxysmal stage Steroid may reduce inflammation and decrease intensity Supportive care Warm mist oxygen Nasopharyngeal suctioning Parenteral fluids Prevention—immunization Neither complete nor permanent 44 AKA Lockjaw 45 Clostridium tetani Gram positive spore forming rods that are obligate anaerobes Flagellated and motile Proliferating cells elaborate one of the most potent toxins known as tetanospasmin Causes systemic toxemia Binds to gangliosides in the CNS Substance suppresses inhibiting influences on motor neurons and interneurons 46 Tetanus-Prone Wounds Usually following a trauma where the spores of C. tetani are punctured into the tissue. Anaerobic environment Consider Burns or Frostbite http://4.bp.blogspot.com/umco405fqqM/Te76TPIHFVI/AAAAAAAAAJE/oITaeGSYXuI/s320/tetanus.jpg Incubation period 3 – 21 days 47 Local form—uncommon Spasm and increased muscle tone at site of injury 2 week progression with recovery in 1 month 48 Generalized tetanus, the most common type (about 80% Usually presents with a descending pattern Starting with trismus or lockjaw Difficulty opening mouth Followed by stiffness of the neck Difficulty in swallowing Rigidity of abdominal muscles Hyperextension of body Hyperactivity of DTR Difficulty in sucking Neonatal tetanus http://2.bp.blogspot.com/_pOK9nKyAFVc/TFpDHrL3J_I/AAAAAAAAAFM/6miUlFsAG 0I/s1600/tetanus.jpg 49 Wound or recent history of wound Without clear history of tetanus toxoid immunization Moderate leukocytosis Normal CSF Normal serum calcium Attempts to culture C. tetani from wound not useful 50 Supportive care until toxin metabolized May need respiratory support Avoid external stimuli Neutralize circulating toxin through tetanal immune globulin (TIG) Passive immunization Active immunization must be started Must consider wounds that are “tetanus-Prone” Debride wounds Does not effect tetanus management Role of antibiotics not clear Conflicting studies Prevention – immunization SAD RATS: Sedation Antitoxin Debridement Relaxant ATB Tracheostomy Stimulants-avoid 51 “Blood loving” 52 Pyogenic infections in young Involve the middle ear, sinuses, facial skin, epiglottis, meninges, lungs, and joints Leading cause of bacterial meningitis worldwide Has almost disappeared from U.S. (vaccination!) Aerobic, pleomorphic, gram negative coccobacilli Encapsulated (Type B) or not (Type A) Type B are more virulent and cause 95% of the invasive bacteremic infections Respiratory droplets and secretions from person to person Serious disease peaks at 6 to 18 months Corresponding to loss of maternal antibodies Incubation period unknown 53 Unencapsulated H. influenzae strains spread locally from their normal sites of residence to adjoining sterile locations Organisms proliferate and elicit acute inflammatory responses Encapsulated—capable of tissue invasion Capsular polysaccharide of type b organisms allows to evade phagocytosis, and bacteremic infections are common Elaborates an IgA protease Facilitates local survival in the respiratory tract 54 Most common cause of meningitis in children younger than the age of 2 Vaccination has reduced this… Bronchopneumonia or lobar pneumonia Fever, cough, purulent sputum, dyspnea Epiglottitis Obstructs upper respiratory tract Septic arthritis Large weight bearing joints Fever, heat, erythema, swelling, and pain on movement Facial cellulitis Fever, profound malaise, raised hot, red-blue discolored area of the face, usually cheek or eye 55 "Explaining Hot Neck Stiffness": [In order from birth to death]: E. coli, Group B Step [infants] H. influenzae [older infants, kids] N. meningitis [young adults] S. pneumoniae [older folks] 56 Gram stain Culture Immunologic assays ELISA or EIA 57 Antibiotics Supportive therapy Prevention Vaccination 58 AKA Streptococcus 59 Second most common cause of vaccine-preventable death in the U.S. After influenza 60 Streptococcus pneumoniae major cause of pyogenic infections Aerobic, gram positive Lancet shaped diplococci Commensal Often have a capsule Increases virulence Infection occurs when organism gains access to sterile sites Prior splenectomy, alcoholism, asthma, HIV infection are predisposing factors Advanced age at high risk of rapid, fulminant septic shock and death 61 Reservoir Human carriers Transmission Respiratory Autoinoculation Temporal pattern Winter and early spring Communicability Unknown Probably as long as organism in respiratory secretions 62 Lobar pneumonia Most common cause of bacterial CAP Bacteremia Meningitis Most common Middle ear infections Usually by age of 5 One of the top two causes Sinuses 63 COMPS: mnemonic Conjunctivitis Otitis media Meningitis Pneumonia Sinusitis Symptoms will depend on what tissue is infected 64 ATB Supportive therapy Prevention—vaccination 65 66 Route of transmission: Fecal-oral transmission Sheds into bile which accounts for presence in feces "Vowels are bowels": Hepatitis A and E transmitted by fecal-oral route Virus is resistant to gastric acid, absorbed by intestine, excreted in bile, shed in stools Spread by poor hand washing, crowding, poor sanitation, contaminated food and water May occur in epidemics or sporadic cases Risks—living in close quarters, household contacts, eating uncooked shellfish 67 Incubation period: Relatively short averages 30 days Rise in aminotransferase (AST) activity Markedly increased (>1,000 IU/dL) ALT commonly higher Virus is shed in stool 2 weeks BEFORE clinical illness, and persists until 1 week after 68 Severity of Illness In kids, most cases are sub-clinical (asymptomatic) or mild and self-limiting In adults, symptoms range from very mild to severe Severity increases with age 30% of Americans are positive for HAV antibody, yet only 3-5% remember having a hepatitis like illness Most are anicteric Most childhood 69 Malaise May cause spiking fevers Myalgia Jaundice Arthralgia Easy fatigability URI like symptoms Anorexia Distaste for smoking Nausea and Vomiting In many cases, jaundice never develops Acholic stools Lacking bilirubin pigment Cholecystitis occasionally complicates the course RUQ pain 70 http://www.vaccineinformation.org/photos/hepaiac001.jpg 71 Hepatomegaly Rarely marked Liver tenderness Systemic toxicity is most often encountered in Hepatitis A 72 Course of Illness Complete clinical and laboratory recovery in about 9 weeks is the usual outcome Causes “acute” hepatitis May last up to a year Relapses may occur before complete recovery Progression to fulminant hepatitis is rare Unless patient has underlying chronic liver disease or Hepatitis C virus infection No carrier state and never chronic 73 Serologic markers Antigen markers: none clinically Antibody markers: Anti-HAV (IgM) is detected (2 weeks) soon after the onset of symptoms and lasts up to 3-6 months (acute markers) Good for dx acute hepatitis A Anti-HAV (IgG) is also detected soon after the onset of symptoms, slightly after Anti-HAV (IgM), but persists for years and provides lifelong immunity IgG anti-HAV indicates previous exposure to HAV, noninfectivity, and immunity Viral RNA tests –not clinically done 74 UpToDate 2011 http://ezproxy.butler.edu:4053/contents/image?imageKey=GAST%2F10091 &topicKey=ID%2F2692&source=see_link&utdPopup=true 75 Supportive Must be cautious about transmission to others by not sharing food or dishes and frequent hand washing Avoid alcohol or all other hepatotoxins Unvaccinated persons who are exposed should receive post-exposure prophylaxis with a single dose of HAV vaccine or immune globulin Vaccination Since 1996, rate has declined 92% 76 77 Etiology: Caused by a hepadnavirus DNA virus More able to be incorporated into the host’s genome Virus consists of a “core” surrounded by an outer surface envelope, each of which is antigenic 78 Routes of transmission Parenteral, sexual, perinatal, transmucosal Virus has been found in blood, saliva, and semen C-Section offers no protection Vertical is the most important route worldwide 79 Route of Transmission Highly prevalent in homosexuals and IVDA Most cases in US heterosexual transmission Others at risk Hemodialysis patients Lab and blood bank workers Healthcare workers Blood transfusion 80 Incubation Period Long –6 weeks to 6 months Average of 3 months 81 Severity of Illness May be asymptomatic, mild, moderate, or fulminant (<1%) Liver damage occurs mainly from the immune response to the virus Typically presents with a non specific flu-like illness and abdominal pain 30% become jaundiced Serum sickness type illness may develop Fever, rash, arthritis, glomerulonephritis, vasculitis 82 Course of Illness Elevations in AST and ALT are higher 90% of HBV are ACUTE Most are asymptomatic and have a complete recovery rate Those who are symptomatic Most of these recover 10% of these develop CHRONIC infection Chronic is indicated by antigen > 6 months Progression is greater in IVDA and male homosexuals <1% of these develop a fulminant course, with high mortality rate—60% 83 Chronic Course of Illness: Chronic “carriers” Carriers mean that they don’t develop the necessary antibodies to clear the antigen > 6 months 2 types of chronic carriers Chronic active have ongoing viral replication Bad prognosis Chronic persistent have minimal, if any, viral replication Much better prognosis A number of patients eventually develop Anti HBV and clear HB Ag 84 85 Serologic markers Antigen markers HBsAg Surface antigen: from the surface of the viral envelope HBcAg Core antigen: from inner core of the virusno test HBeAg Envelope antigen: a secretory form of viral core antigen—maximally infective time frame 86 Serological Markers HBsAg First lab evidence of HBV infection Even before AST and ALT Indicates that patient is infected and infectious 87 HBeAg Rises about the same time but declines before HBsAg Implies ongoing viral replication and greater infectivity If present beyond 3 months, there is increased likelihood of chronic infection 88 Anti-HBc (IgM) The first evidence of host response to the infection Implies a more recent infection IgM HBcAg alone in serum indicates False positive test Latent infection in HBV DNA Anti-HBc (IgG) Rises at the same time as the IgM form, but lasts indefinitely 89 Anti-HBs (IgG) Occurs after the clearance of HBsAg, about 4-6 months after the initial infection Occurs after immunization with vaccine Disappearance of HBsAg and the appearance of anti-HBs signal recovery from HBV infection, noninfectivity, and immunity 90 HBV-DNA The viral DNA can be detected and measured The most sensitive and specific marker of viral replication and infectivity Interpretation of HBV-DNA values Normal/desired: 0 pg/mL Low viral replication: <200 pg/mL High viral replication: >200 pg/mL 91 http://www.medscape.com/viewarticle/743651_3 92 “Carrier State” Chronic HBV (= antigen > 6 months) Chronic carriers don’t develop Anti-HBsAg and therefore continue to carry (+)HBsAg Chronic active if (+)HBeAg with ongoing viral replication Chronic persistent if (-) HBeAg with minimal (if any) viral replication Chronic non carriers Eventually develop Anti-HBs and clear HBsAg 93 Antiviral Interferon Avoid hepatotoxins With chronic hepatitis B Monitor for hepatocellular carcinoma AFP USN Prevention Recombinant Vaccination Immunoglobulin 94 Polio or Poliomyelitis 95 Global effort to eradicate disease 350,000 cases in 1988 to 1,604 in 2009 Afghanistan, Pakistan, Nigeria, India still epidemic Single stranded RNA virus Enterovirus Fecal – Oral or Oral transmission Highly contagious Incubation period 9 – 12 days from exposure 96 95% asymptomatic Those who become ill Abortive poliomyelitis Nonparalytic poliomyelitis Paralytic poliomyelitis 97 Abortive poliomyelitis—clinically only suspected during epidemics Minor illness Fever HA Vomiting Diarrhea Constipation Sore throat 98 Nonparalytic poliomyelitis—indistinguishable from viral meningitis Similar symptoms of Abortive, plus Meningeal irritation Muscle spasm Absence of frank paralysis 99 Paralytic poliomyelitis Two forms Spinal poliomyelitis Muscles innervated by the spinal muscles Bulbar poliomyelitis Weakness of muscles supplied by the cranial nerves (CN IX and X) and of the respiratory* and vasomotor centers Review: What are CN IX and X? CN: IX—Glossopharyngeal CN X: Vagus Paralysis may occur at any time during febrile period Tremors Muscle weakness Constipation Ileus 100 Cerebrospinal fluid pressure and protein are normal or slightly increased Glucose is not decreased The virus can be recovered from throat washings and stool Neutralizing and complement fixing antibodies appear during the first or second week of illness Serologic testing cannot distinguish between wild-type and vaccine related virus infections What does wild-type mean? 101 Hospitalized Strict bed rest Reduces rates of paralysis Medically manage fecal impaction and urinary retention In cases of respiratory weakness, intensive care Refer with neurologic compromise Reportable condition Prevention—vaccination 102 103 Orthomyxovirus Transmitted by the respiratory route—droplet Viruses further subtyped based on the Hemagglutinin (H) and Neuraminidase (N) Annual epidemics usually appear in fall or winter Incubation period is usually 1 – 4 days 104 Fever Lasts 1 – 7 days Chills Malaise Myalgias Substernal soreness HA Nasal stuffiness Nausea Nasal obstruction, sneezing, and sore throat—Coryza "Having Flu Symptoms Can Make Moaning Children A Nightmare": Headache Fever Sore throat Chills Myalgias Malaise Cough Anorexia Nasal congestion 105 Pharyngeal injection Flushed face Conjunctival redness Moderate cervical lymph nodes Fever 106 Leukopenia common Leukocytosis may occur Virus may be isolated from throat or nasal washings RIA or EIA may be used 107 Rest Antivirals Analgesics Supportive therapy Monitor for secondary bacterial infections Avoid aspirin in children Reye syndrome—fatty liver (leading to failure) with encephalopathy Prevention—vaccination if not contraindicated 108 Rubeola or Morbilli 109 The New York Times (7/6, Harris) reported, "An increase in the number of measles outbreaks in Europe, Asia and Africa in recent months is cause for concern at the Centers for Disease Control and Prevention in the" US. CDC spokesperson Candice Burns Hoffman, "said in a release that the United States was experiencing 'the highest number of measles cases since 1996,' in large part because of unvaccinated travelers recently returned from" abroad. "As of June 17, 156 cases of measles from at least 25 states had been reported to the center this year." 110 Single stranded RNA virus Paramyxoviral infection Respiratory aerosol and secretions Person to person Highly contagious 111 Fever About four days or so Up to 104oC Cough Nasal obstruction, sneezing, and sore throat—Coryza Red eyes—Conjunctivitis Stimson Line Rash— http://www.health24.com/medical/Conditio n_centres/777-792-823-1838,46960.asp Develops on head several days after fever Spreads to cover the rest of the body 112 http://missinglink.ucsf.edu/lm/IDS_105_skinILM/measles_files/image002.jpg 113 http://sciencephoto.com/image/259736/530wm/M2100363Koplik_s_spots_in_measles-SPL.jpg 114 Typically clinical diagnosed Leukopenia usually present Thrombocytopenia common Virus may be cultured Detection of IgM measles antibodies with ELISA or a fourfold rise in serum hemagglutination inhibition antibody supports the diagnosis Fluorescent antibody staining 115 Isolation with bed rest until afebrile Symptomatic therapy Antipyretics and fluids Vitamin A Maintains gastrointestinal and respiratory epithelial mucosa Antivirals have been used ATB for any secondary bacterial infections Reportable condition 116 117 Single stranded RNA virus—Paramyxovirus Infection of salivary glands Primarily the parotid glands Person to person Respiratory route Highly contagious Incubation period 18 days Cell necrosis, inflammation, mononuclear cell infiltration 118 Fever Headache Muscle aches Malaise Anorexia Swollen salivary glands Parotitis Bilateral or unilateral 7 – 10 days 119 http://www.health.gov.on.ca/en/public/programs/mumps/images/m ohltc_mump_boy.jpg 120 Orchitis Most common complication in males Rarely, infertility Unilateral Oophoritis Meningitis Pancreatitis Exhibit elevated serum amylase activity Mastitis Deafness 121 Usually a clinical diagnosis Isolate virus Serologic diagnosis by complement fixation test IgM antibodies by ELISA 122 Supportive therapy Isolation of patient until glandular swelling subsides Usually noncontagious 9 days after onset of parotid swelling Reportable condition Prevention Live attenuated vaccine 123 Orchitis Oophoritis Infertility Meningoencephalitis Pancreatitis Prostatitis Nephritis Myocarditis 124 In German, means “little red” AKA—German Measles Way to remember: think of a German ringing a little red bell… 125 Rubella Virus Single stranded RNA Togavirus family Spreads person to person Primarily the respiratory route Incubation period 14 to 18 days Virus shed during this time 126 What is the classic acronym of the five perinatal infections with similar presentations, including a rash and ocular findings? ToRCHeS: T: Toxoplasmosis O: Other (Syphilis) R: Rubella C: Cytomegalovirus (CMV) H: Herpes Simplex Virus (HSV) Toxoplasma Other—parvovirus, listeria Rubella CMV Herpes simplex, Herpes zoster (varicella), Hepatitis B,C,E HIV Enterovirus Syphilis Other diseases have been added! 127 Teratogenic in (early) pregnant women *Deafness Cataracts / Glaucoma / Retinal Defects Heart defects Pulmonary valvular stenosis, pulmonary artery hypoplasia, VSD, PDA Mental retardation Blueberry (muffin) spots Microcephaly / mental retardation Premature delivery Death Maternal infection after 20 weeks gestation usually does not cause significant fetal disease http://lessons4medicos.blogspot.com/2009/05/grey-baby-syndrome-bluebaby-syndrome.html 128 Most patients Mild febrile disease—many asymptomatic postnatally Rhinorrhea Conjunctivitis Postauricular lymphadenopathy Arthritis Forscheimer Spots on Palate Petechiae on palate – are not pathognomic 129 Rash Rapid Spread from face to trunk and extremities Lasts one to three days—Range 1 – 8 days Therefore, in past known as three day measles Also third exanthem in childhood Onset of rash—decrease in viremia Rash immune mediated? Presence of neutralizing antibodies http://www.health24.com/med ical/Condition_centres/777792-823-1838,46960.asp 130 http://ezproxy.butler.edu:4053/contents/image?im ageKey=ID%2F12261&topicKey=ID%2F8301&source =see_link&utdPopup=true 131 Detection of rubella-specific IgM antibodies using an enzyme immunoassay May isolate virus Rare Supportive care Reportable disease Prevent with vaccination Live attenuated virus 132 AKA Chickenpox and Shingles 133 HHV-3 Highly contagious— Inhalation of infective droplets Especially day before rash erupts Contact with lesions 134 Generally disease of childhood Incubation period of 10 – 20 days 135 Fever Malaise Mild in children; more marked in adults 136 http://www.health24.com/medical/C ondition_centres/777-792-8231838,46960.asp Pruritic Begins prominently on face, scalp, and trunk Later involves extremities to a lesser extent Maculopapules change in a few hours to vesicles These become pustular and eventually form crusts Crusts slough in 7 to 14 days http://www.fastchickenpoxcure.com/ blog/wpcontent/uploads/2011/02/chickenpox-stage.jpg 137 http://www.healthcare.uiowa.edu/dermatology/Images%5CClin%5CVaricel02.jpg 138 New lesions may erupt for 1 – 5 days Different stages of the eruption are usually present simultaneously CROPS 139 http://www.vaccineinformation.org/photos/variaap001.jpg 140 After the primary infection, the virus remains dormant in cranial nerves sensory ganglia and spinal dorsal root ganglia Latent VZV will reactivate as herpes zoster 10 – 30% 141 Incidence increases with age—more than half are > 60 years of age Due to age related decline in immunity against VZV Pain often severe and commonly precedes the appearance of rash Acute neuritis Lesions follow a dermatomal distribution Usually thoracic and lumbar roots Usually unilateral http://www.health24.com/medical/Condition_centres/777-792-823-1838,46960.asp 142 Lesions on the tip of the nose, inner corner of the eye, and root and side of the nose—Hutchinson sign Indicate trigeminal nerve involvement http://eyewiki.aao.org/images/1/1/14/Herpes-zoster-ophthalmicus-395X275.jpg 143 Facial palsy, lesions of the external ear with or without tympanic membrane involvement, vertigo and tinnitus, and deafness Signify geniculate ganglion involvement Ramsay Hunt Syndrome 144 Etiology: Reactivated Herpes zoster Complication: Reduced Hearing 145 Post Herpetic Neuralgia Most common complication ~15% 146 Diagnosis made clinically PCR 147 Antiviral Analgesic for acute neuritis 148 149 Neisseria meningitidis Gram negative intracellular diplococci Typically serogroup C in U.S. 40% are nasopharyngeal carriers of organism Disease develops in relatively few Clinical illness may take the form of Meningococcemia Meningococcemia with meningitis Meningitis 150 High fever, stiff neck, HA are classic signs Chills Back, abdominal, and extremity pain Nausea and vomiting Rapidly developing confusion, delirium, seizures, and coma occur in some 151 Nuchal and back rigidity Pain with neck flexion Kernig sign http://www.youtube.com/watch?v=rJ-5AFuP3YA Brudzinski sign http://www.youtube.com/watch?v=jO9PAPi- yus&feature=related 152 Appearing generally in the lower extremities and at pressure points Vary in size from pinpoint to large ecchymoses Skin gangrene can occur http://www.health24.co m/medical/Condition_c entres/777-792-8231838,46960.asp 153 http://www.meningococcal.org/images/page_images/513.jpg 154 Lumbar puncture—delay until clinically stable Cloudy or purulent cerebrospinal fluid Increased pressure Increased protein Decreased glucose PMNs predominating Gram negative intracellular diplococci gram stain May culture Gold Standard is CSF culture 155 Supportive care Blood cultures IV fluids IV ATB Prevention Vaccination Prophylactically eliminating nasopharyngeal carriage— ATB 156 HPV 157 Nonenveloped Invade cutaneous and mucosal epithelium, proliferate, and cause warts Most transient Those that persist are problematic 158 Common skin warts—verucca vulgaris Hands and feet often Typically asymptomatic Plantar may be painful with pressure Vary in size and shape May be flat and superficial Plantar and deep Plantar warts lack dermatoglyphics—ridges, whorls, and loops of sole print filiform 159 • Laryngeal warts • May obstruct airway in children—removed surgically • Commonly transmitted during childbirth—vaginal canal • Anogenital warts—types 6 and 11 • AKA Condyloma acuminata • Sexually transmitted • May be cancerous • Cervical warts—types 16 and 18 Sexually transmitted 160 Histologic sampling With acetic acid develop acetowhitening Easier to biopsy Hyperplastic prickle cells with excess keratin—common warts Koilocytotic or vaculoated squamous epithelial cells in clumps—cervical warts HPV DNA in cervical swabs using molecular probes 161 Spontaneous remission Recurrence common Liquid nitrogen Salicylic acid Immune modulators Surgical removal Prevention— Condoms Vaccine 162 Post-Lecture 163 The major virulence factor of Corynebacterium diphtheriae is A. B. C. D. E. Ability to multiply within macrophage Capsule Endotoxin Exotoxin Neurotoxin 164 The major virulence factor of Corynebacterium diphtheriae is A. B. C. D. E. Ability to multiply within macrophage Capsule Endotoxin Exotoxin Neurotoxin 165 The exotoxin elaborated by C. diphtheriae causes a pseudomembrane to form in the pharynx and is absorbed by the circulatory system where further damage ensues Physician Assistant Review Lippincott Williams and Wilkins 2001 166 A physician assistant student presents to the primary care office with a lesion on his foot. History reveals he walks barefoot in the shower at the local wellness center (gym). The lesion on the bottom of the foot is flat and has grown inward. There is another lesion on the side of the foot that appears filiform. Which of the following is most likely the causative agent? A. B. C. D. E. Coronavirus Papilloma virus Poxvirus Rubella virus Togavirus 167 A physician assistant student presents to the primary care office with a lesion on his foot. History reveals he walks barefoot in the shower at the local wellness center (gym). The lesion on the bottom of the foot is flat and has grown inward. There is another lesion on the side of the foot that appears filiform. Which of the following is most likely the causative agent? A. B. C. D. E. Coronavirus Papilloma virus Poxvirus Rubella virus Togavirus 168 Where does the rash begin in cases of rubella? A. B. C. D. E. Back Chest Head/neck Inguinal region Wrist 169 Where does the rash begin in cases of rubella? A. B. C. D. E. Back Chest Head/neck Inguinal region Wrist 170 A three year old, unknown to your clinic previously, presents and has a high fever, cough, coryza, conjunctivitis, and a rash. Koplik spots are noted on the buccal mucosa. The conjunctivae reveal a transverse line of inflammation along the eyelid margin (Stimson line). The rash is morbiliform, began on the head, and then spread over most of the body in a descending fashion within 18-20 hours. This clinical presentation is consistent with a diagnosis of A. B. C. D. E. Herpes Zoster Human Herpesvirus-6 Measles (Rubeola) Rubella (German, 3-Day Measles) Meningiococcal 171 A three year old, unknown to your clinic previously, presents and has a high fever, cough, coryza, conjunctivitis, and a rash. Koplik spots are noted on the buccal mucosa. The conjunctivae reveal a transverse line of inflammation along the eyelid margin (Stimson line). The rash is morbiliform, began on the head, and then spread over most of the body in a descending fashion within 18-20 hours. This clinical presentation is consistent with a diagnosis of A. B. C. D. E. Herpes Zoster Human Herpesvirus-6 Measles (Rubeola) Rubella (German, 3-Day Measles) Meningiococcal 172 All pictures, audio, video previously referenced. CDC Vaccines and Preventable Diseases http://www.cdc.gov/vaccines/vpd-vac/default.htm Current Medical Diagnosis and Treatment 2011, 50th ed. McPhee SJ, Papadakis MA McGraw Hill 173