Tissue Injury Exam 5

Prions - know these. (A) What (list) types of diseases can prions cause? (B) how are they "infectious"/ prion disease results from what? {think: molecular model} (C) How would you get "Spontaneous Prion Disease", and is there a treatment for it?

"Proteinaceous Infectious Particles = Prions" (A) Chronic Degenerative Neuropathies caused by Prions [e.g's. Bovine Spongiform Encephalopathy (BSE, Mad Cow Disease), Scrapie (sheep), Creutzfeldt-Jajob (CJD), & Kuru (meaning "to tremble"). (B) Changes conformation of PrP proteins in NEURONS s.t. act as "seed" to convert more of this protein to abnormal, so they stick together (norm. separate) and form "amyloid" fibers. (C) Spontaneous Prion Disease (often Hereditary predisposition, inherited mutation in PrP gene): 1. Ingestion of prions [NO TRANSMISSION, they are infectious proteins WITHOUT NUCLEIC ACID GENOME] - they extreme resistant to irradiation, boiling, dry head, many chemicals {formalin, alcohols} since their version of PrP complexes {amyloid fibers} are very stable to disruption so they are very resistant to those conventional inactivation procedures. 2. No Treatment.

Forms of available prevention and treatment for viral infections?

"Viral infections can (Sometimes) be prevented and treated" Treatment = Antivirals (specific, no broad-spectrum); No antibiotics (<- bc they target bacteria - live organisms with metabolism. Viruses are metabolically inert.). Prevention = Hygiene, lifestyle changes, vaccines {= vaccination is induction of antibodies and other immune mechanisms to prevent infectious disease}.

(1) Which one of the following statements concerning diarrhea is FALSE? A. Bloody diarrhea (dysentery) is due to damage to the wall (epithelial layer) in the large intestine. B. Infection of the small intestine typically leads to secretory diarrhea. C. Cholera toxin and ETEC heat-labile toxin are AB subunit toxins that cause increased salt uptake by epithelial cells. D. Diarrheal pathogens are typically spread by the fecal-oral route. E. Enterohemorrhagic E. coli (EHEC) can cause systemic disease (kidney failure) without actually spreading systemically. (2) Differentiate between "Watery diarrhea" and "bloody diarrhea"

(1) Answer C. Watery diarrhea is when salt leaves the cell and water follows it. E is true statement because EHEC E.Coli produces toxins so can cause issues throughout body. (2a) Watery Diarrhea = small bowel = - Cholera Toxin - E. coli (heat-labile toxin; enterotoxigenic E. coli [ETEC]). - Rotavirus - Norovirus - Giardia Lamblia - Cryptosporidium = Mid-abdomen pain = large stool, watery. = bc salt leaves (toxin impact on ion channels) and water follows. (2b) Bloody Diarrhea = large bowel = - Shigella (shiga toxin) - E. Coli (shiga toxin producing STEC). - Campylobacter = Lower ab / rectum pain. = small stool, mucoid & bloody. = bc damage to wall in Lg. intestine.

(1) Which one of the following statements concerning Helicobacter pylori is FALSE? A. Antibiotics are effective for treating acute infections and preventing ulcers, but the bacterium is never cleared from the stomach. B. This bacterium can colonize the stomach. C. This bacterium is acquired orally. D. This bacterium produces urease, an enzyme that converts urea to bicarbonate and ammonia. E. Few people in the United States of America are infected with this pathogen. (2) Helicobacter Pylori - (1) How does it get in, then what damage does it cause to you? (2) Treatment once you're infected?

(1) Answer is A. antibiotics are effective at clearing H.pylori from stomach. (2) Fecal-Oral, or Oral-ORAL => colonizes STOMACH, can spread and colonize duodenum: must BUFFER pH to grow/multiply in stomach via UREASE {cytoplasmic enzyme, converts urea and water to ammonium and bicarbonate} => Ulcers; Vacuolating Cytotoxin and Host Inflammatory Reaction Damages Mucosal Layer; Chronic Damage; Cancer. - Antibiotic Therapy targeted at H. Pylori -> full recovery. - Case: non-smoking, gastro-esophageal reflux, history HALITOSIS (BAD BREATH) that she couldn't find/docs couldn't find treatment for; no loss of teeth, little caries; family history of H. pylori infection; antibody titer positive for gram-negative bacterium so she was put on antibiotic therapy -> halitosis stopped, and months later reduction of bacteria shown in antibody titer (serological test).

Antivirals - (1) which would be toxic, and which would be efficient and safe? (2) Basic structure

(1) Antivirals are form of treatment for viral infections, but there are so few made because... - Most chemicals that block viral replication also block cell replication and so are TOXIC to the host (recall: viruses rely on the cell machinery to replicate), so the GOAL of antiviral therapy is to kill the virus WITHOUT damaging the host. - Difficulty to make EFFICIENT and SAFE antivirals i.e. those that target virus (do not infect uninfected cells bc the uninfected cells lack the virus's enzymes required; and preferentially block virus DNA polymerase but not cellular one} but not the host by finding and exploiting subtle differences in replication. (2) Nucleoside Analogs - nucleosides are building blocks of DNA used by DNA polymerase. (3a) Acyclovir (acycloguanosine) - used to manage HSV and VZV infections = TARGETs HSV (or VZW) DNA Polymerase; so the HSV DNA polymerase incorporates DRUG, iNSTEAD OF NORMAL physiological nucleotide deoxy triphosphate -> hsv DNA polymerase cannot continue with DNA synthesis because the drug triphosphate lacks 3'OH and get STALLED = SAFE ANTIVIRAL BECAUSE it does not affect uninfected cells {since those cells don't have the virus's enzyme, which drug needs to happen to get in} and does not inhibit "cellular" DNA polymerase {since it preferentially blocks the virus's DNA polymerase, but not cellular DNA polymerase}. (3b) Ganciclovir - used to manage CMV infections

(1) Antigenic Variation in Influenza (2) Antigenic Drift (3) Antigenic Shift know this - influenza

(1) Because HA and NA are on the viral surface, they serve as antigens so they trigger immune system to produce antibodies. If person infected with Flu virus in past, now the exactly same virus will NO LONGER cause disease because its HA and NA will be recognized by pre-existing antibodies and the immune response will quickly clear the infection. However, if either HA or NA sequence changes even slightly, pre-existing antibodies will no longer recognize this new, mutated virus, and the infected person will get sick. (2) Antigenic Drift = gradual small variation (point mutation) in HA or NA makes it difficult to be recognized by pre-existing antibodies (is because viral RNA polymerase is error prone aka makes mistakes but does not correct them). Why we get sick with flu over and over (seasonal EPIDEMICS). And why Flu vaccines are made annually/ needs to be repeated each year (strains of influenza of variation). (3) Antigenic Shift = dramatic/large change in HA or NA (makes it impossible to be recognized by pre-existing antibodies). Why we experience occasional pandemics (2009 swine flu). Fears of bird flu epidemic. - Exchange / REASSORTMENT of genome segments between avian and mammalian virusses - ONLY IN TYPE A. Results in PANDEMICS (irregular, 10-50 yr intervals), can also result in epidemics. - KNOW WHEN REASSORTMENT HAPPENS (IN PIG): for genome segments to be exchanged, one species would have to be infected with at least two (more than 1 type) very different flu viruses; e.g. human and avian. Know that some flu strains are better at infecting humans while others are better at infecting avians bc DIF CELL RECEPTOR USAGE (human flu HA binds dif. sialic acid receptor than avian) & AVIAN RNA POLYMERASE FUNCTIONS POORLY IN HUMANS. But reassortment can happen in a PIG (bc both human flu virus and avian can meet in pig and infect) s.t. it gets infected with an avian and human influenza and can act as a mixing vessel for dif strains, seen in dense populations of SOUTHEAST ASIA. The CONCERN is that there will be a reassortment of bird and human flu resulting in very contagious and virulent strain, but luckily (in red")"avian virus has not yet acquired the ability to infect humans easily or to be passed efficiently from person to person".

"How do viruses propagate?" (1) Growth via? Stages of Growth Curve? (2) Early vs. late gene expression (in viral replication cycle)? (3) List of what viruses need to do to replicate? know this.

(1) Binary Fission growth. GROWTH CURVE 3 STAGES: - Stage One: Virus used in infection slowly declines. = incoming viral particle is disassembled inside the new host cell, initiating the next infectious cycle (these particles are delivery devices for transmission of the genome from cell to cell but are not alive). - Stage Two: "Eclipse Stage" w. no virus detected in the media. Is between early gene expression and late gene expression = Within host, viral genome makes stuff it needs for viral replication and its transmission within viral particles. - Stage Three: "Burst" produced by a single cycle of viral replication = Hours after infection= New viral particles are de novo assembled (from newly synthesized components within host cell) and released. (2) Early proteins/early gene expression = enzymes needed to replicate genome. Late proteins/gene expression = structural proteins for virion assembly. Followed by assembly and exit (egress). (3) Enter the host cell and uncoat the genome. Make viral mRNA. Make viral proteins. Replicate viral genomes. Form progeny virions. Leave the host cell.

(1) Which of the following statements regarding viral pathogenesis is TRUE? A. Urogenital route, generally speaking, is the most common route of viral transmission. B. All viruses cause disease at the site of entry. C. Viral spread within the host typically involves bacteremia. D. Viral tropism is defined by accessibility, susceptibility, permissibility, and the availability of the antiviral defenses of the host. E. All of the statements are correct. (2) Viral encounter, entry, spread?

(1) D is answer. VIRAL ENCOUNTER: Contact with... 1) Infected Person 2) Infected Insect or Animal 3) A component of the environment e.g. contaminated water, food, soil. VIRAL ENTRY: typically mucosa of respiratory, gastrointestinal, or urogenital tracts, cornea, or skin. VIRAL SPEAD: after replication at site of entry, infection can remain localized or spread to other organs {<- disseminated infection}. - Bacteremia has nothing to do with virus.

GI Tract (1) Anatomy - know (2) General Defenses to Infection - know (3) What causes breaks in the defenses?

(1) GI tract is - exterior {topologically exterior}. - compartmentalization via gates and valves: mouth; gastroesophageal (GE) junction; sphincter of oddi; Ileal-Cecal Junction. (2) Defences: a. Barriers: Continuous epithelium, Mucus, Constant shedding of Epithelial Cells. b. Flow: Saliva, Drinking, Peristalsis. c. Normal Flora {Intestinal Microbiota}: = immune stimulation, keep out invaders {competition}, role in nutrition {egs, vitamin K, biotin} - note: but also, intestinal macrobiotic can be bad: source of infection {e.g. following trauma}, & produce carcinogens. d. Host Defensive Molecules: Mouth {lysozyme, ROS, salivary peroxidase}, Stomach {HCl, digestive enzymes}, Small Bowel {bile acids, pancreatic juice, cationic proteins, IgA}, Large Bowel {low molecular weight Fatty Acids; IgA}. (3) Breaks in defenses = Achlorhydria (Hcl low), Altered Flow {Diverticula}, Antibiotic Use.

Shigellosis- (1) infection of what (one specific characteristic/sign of disease), and Pathogens that cause this?(2) How does it get into you and what damage does it cause? Antibiotics?

(1) infection of LARGE bowl resulting in severe diarrhea w. BLOOD and mucus in feces = Bacillary Dysentery {=Shigellosis} = caused by 4 pos. species: Shigella dysenteriae {shiga TOXIN produced, most SEVERE disease}, Shigella Flexneri, "" Boydii, "" Sonnei {least severe disease}. (2) Fecal Oral Route or direct contact spread => non-motile entry aka surface proteins mediate invasion into normally non-phagocytic colon epithelial cells => its an intracellular pathogen so spreads cell-to-cell, and multiplies in cytoplasm of host cells => causes local ulcerations due to cell death from bacterial growth; and causes host inflammatory reaction; and shiga toxins cause damage => rarely severely dehydrating, antibiotics are CRUCIAL for cases with fever and/or dysentery {problem with drug resistance}; also, malnutrition can results from damaged (lg. intestine) epithelium. (3) Mechanism of Shiga Toxin Action = A-B Toxin - A subunit is an ENZYME (multiple places, so a single subunit can kill a cell bc can kill many in cell) that blocks ribosomal translation and causes damage to large intestine epithelium, resulting in bloody diarrhea. Case: 22 month old girl lives low income area (near mexican border) became febrile, got watery diarrhea. Next day, less diarrhea, but plus bloody stool. Stools small in volume, but inc. frequency and blood content. Parents too infant to ER, found her mild dehydrated with hyperactive bowel sounds and 104F fever. Stools with large # WBCs. Once doc suspected bacillary dysentery (shigellosis), they put her on IV fluids to rehydrate and gave her antibiotics -> saved her the damage that pathogen can cause to her large intestine epithelium.

(a) Three main infectious routes into the CNS (ID 3/16) know these definitions.

(A) "CNS infections require means of entry into well protected CNS (trauma, nerves, from blood stream)" 1. Hematogenous route: from bloodstream into CSF thru choroid plexus. 2. Neural Route: migration e.g. up trigeminal nerves. 3. Trauma to CNS: direct inoculation of pathogenic microbes into CNS.

Carbon Monoxide - most common cause of? Impact on your body (biology)? Acute poisoning is characterised by? know this

* Most common direct chemical cause of death! * Limits capacity of hemoglobin to carry oxygen: * hemoglobins affinity for CO is 200x greater than affinity for oxygen. - oxyhemoglobin is displaced by carboxyhemoglobin (incapable of carrying oxygen). - systemic hypoxia when oxygen 20-30% saturated. - unconsciousness or death at 60-70% saturation. * Acute Poisoning is characterized by Cherry-Red Color of the Skin and ORAL mucosa. - Systemic hypoxia may result in irreversible impairment of memory, vision, hearing, or speech. Environmental Toxin. Colorless, non-irritating, tasteless, odorless gas. Produced by oxidation of carbonaceous materials. Chronic poisoning may develop in employees working in confined environments.

Mercuric Chloride (Mercury poisoning) know this

* Most exposure today from ingested seafood. * Textile industry historically utilized significant amounts of mercury. * Acute focal gastrointestinal ulceration with severe renal damage (+ widespread necrosis and calcification of proximal convoluted tubules).

Alcohol Abuse know this

* Chronic Alcoholism has multiple effects: - LIVER: fatty change, alcoholic hepatitis, and cirrhosis, & portal hypertension or hepatocellular carcinoma). - GI TRACT: bleeds from gastritis, gastric ulcers, variices. - ACUTE and CHRONIC PANCREATITIS. - Oral, esophageal, larynx, liver ,and breast CARCINOMAS (risk increased with tobacco). - CV SYSTEM (e.g. alcoholic cardiomyopathy). Cerebral Dysfunction: Wernicke-Korsakoff Syndrome (alcoholic encephalopathy) . - FETAL ALCOHOL SYNDROME = microcephaly, mental retardation, facial and cardiac defects. Metabolism of Ethanol = Catalase, Cytochrome P-450 Enzymes; Alcohol Dehydrogenase. Acute Alcoholism (all. abuse) = CNS depressant, may induce reversible hepatic (hepatic steatosis) or gastric (ulceration and gastritis) change; associated w automobile and industrial accidents, homicide, and suicide; acute intoxication may cause death.

Aspirin know this

* Chronic toxicity - Gastroduodenal bleeding * Reye syndrome - Encephalopathy following acute, febrile, viral illness in child - Almost always in association with aspirin use. The number of cases has dropped dramatically since this link was discovered and doctors started advising against giving aspirin to kids and teens, especially during viral illnesses.

Thermal Injury Classification know this

* First-Degree Burns (partial Thickness) = epithelium only involved. * Second-Degree (partial thickness) = epithelium and superficial dermis involvement. * Third and Fourth-degree (full-thickness) = damage to epidermis, dermis, and dermal appendages; skin nd underlying tissue often charred and blackened; often requires skin grafting. Superficial Burns: - 1st and 2nd deg. burns. - epithelium may regenerate. - painful but not serious. Deep Burns: - 3rd and 4th degree burns. - all epithelium destroyed - dermis and appendages damaged. - heal by scarring. - may result in contractors of joints and disfigurement. Complications: 1) Inhalation of smoke or toxic fumes - pulmonary or systemic damage. 2) Hypovolemia - fluid and electrolyte loss. 3) Curling ulcer - acute DUODENUM ulcer associated w severe burns. 4) Infection - most common cause of late fatalities; Pseudomonas Aeruginosa is most freq. organism.

Tobacco - most common cause of what? Associated with an increased risk of? know this

* MOST COMMON exogenous cause of cancer . * 90% of lung cancers. * Cigarettes, snuff, chewing tobacco all harmful to health and associated with increased risk of ORAL cancer. * Substances found in cig smoke: 1. Nicotine = addictive, not carcinogenic. 2. Carbon Monoxide = toxic, not carcinogenic. 3. Carcinogens = Tar, Polycyclic aromatic hydrocarbons, Nitrosamines. Tobacco is associated with: [know this list] - squamous cell carcinoma of larynx. - squamous cella nd small cell bronchogenic carcinoma. - transitional cell carcinoma (urinary bladder). - chronic obstructive pulmonary disease. - atherosclerosis. - other vascular occlusive diseases e.g. Buerger Disease. Active Smoking + Cancer Associations = Lung, Oral Cavity, Esophagus, Pancreas, Bladder. Effects of Tobacco Smoke (substance => effect): 1. Tar => Carcinogenesis 2. Polycyclic Aromatic Hydrocarbons => carcinogenesis. 3. Nicotine => ganglionic stimulation and depression, tumor promotion. 4. Phenol => tumor promotion; mucosal irritation. 5. Benzopyrene => carcinogenesis. 6. Carbon Monoxide => impaired oxygen transport and utilization. 7. Formaldehyde => toxicity to cilia; mucosal irritation. 8. Oxides of Nitrogen => toxicity to cilia; mucosal irritation. 9. Nitrosame => Carcinogenesis Other Active Smoking Associations = Chronic Bronchitis, Emphysema, Atherosclerosis and MI, Spontaneous abortions and preterm birth.

Lead know this

* Primary sources historically included gasoline and lead paint. * Uptake in TEETH and bones (80-85% uptake) with half-life up to 30 years. * 5-10% remains in blood = peripheral neuropathies in adults that can reverse with treatment ; CNS effects in children e.g. low IQ and hyperactivity (+poor organizational skills). * Lead Toxicity => Encephalopathy, Neuropathy, Lead Gingival Line, and Increased Radiodensity of the Epiphysis of long Bones [know all this]. Toxic Amounts -> Blood Changes => Basophilic Stippling of Erythrocytes & Hemolysis of Erythrocytes & Anemia {<- impaired incorporation of iron into heme}. [<- know all that for sure]. Peripheral Neuropathies often resolve with Elimination of Exposure.

Epstein-Barr virus (EBV) - how is it transmitted? environment you'd find it in?Treatment? know this

- Almost Everywhere (ubiquitous) [>90% adults in Western Europe and North America are infected] - Transmission by contact with saliva, in particular, through kissing - EBV PRIMARY INFECTION: Children: asymptomatic; vs; Adolescents (50%): infectious mononucleosis (mono or a "kissing disease") EBV entry, spread, multiplication: - Infection begins in EPITHELIAL CELLS of the mouth and the pharynx => EBV then enters underlying tissues and infects B lymphocytes => Latency in B LYMPHOCYTES (lymphotropic virus). - Low-grade virus replication and shedding in the epithelial cells of the pharynx of all seropositive individuals [At any time, ~20% of infected people have virus in their saliva] Diagnosis: [: EBV infectious mononucleosis ] - Hematologic: complete blood count = high lymphocyte counts, *>10% atypical lymphocytes* , EBV INFECTS B lymphocytes - Clinical: White exudate on tonsils, pharyngitis; Fever, extreme fatigue ; Lymphadenopathy, splenomegaly (rarely hepatitis); INFECTED B LYMPHOCYTES SPREAD TO SPLEEN, LIVER, AND LYMPH NODES. - Serologic: MONOSPOT test - TRANSIENT appearance of EBV-SPECIFIC HETEROPHILE antibodies [Permanent emergence of antibodies to EBV]. Treatment of infectious mononucleosis: Supportive therapy = Self-resolving infection; ANTIVIRALS NOT EFFECTIVE AGAINST EBV MONONUCLEOSIS; Antipyretics; Avoid sports (risk of spleen rupture); Steroids reserved for specific indications: severe splenomegaly, tonsillar obstruction of airways. - Typically, EBV mononucleosis occurs only once. EBV and tumors: -LYMPHOMAS [lymphoid cells]. - NASOPHARYNGEAL CARCINOMA carcinoma (NPC), GASTRIC CARCINOMA, & ORAL HAIRY LEUKOPLAKIA [epithelial cells]. - EBV reactivation (primarily) {note: EBV reactivation is relatively rare and results in several types of tumors. Reactivation typically occurs in the immunocompromised people but is also known as an endemic disease} = Endemic disease = BURKITT'S LYMPHOMA [Type of Non-Hodgkin's lymphoma; Affects jawbone; parts of Africa and Papua New Guinea; Children.] EBV reactivation in the immunocompromised: = Oral hairy leukoplakia (NOT Candida thrush!) - Non-painful white plaque along the lateral tongue borders. - Lesions are adherent, and only the most superficial layers can be removed by scraping - Caused by REACTIVATION of latent EBV, benign. - EBV actively replicates and can be treated with acyclovir. - Common in HIV/AIDS patients.

Kaposi's Sarcoma herpes virus (KSHV, HHV-8)

- Classic Kaposi's sarcoma (KS) - Low prevalence, except elderly Italian and Ashkenazi Jewish men [Endemic in equatorial Africa (adult men); Lesions (purple, brown) on legs and feet] - Epidemic KS in AIDS patients = Very common - 20% frequency; Lesions in different parts of the body; sometimes found in the lining of the mouth DURING A REGULAR DENTAL CHECK-UP.

Genital herpes (HSV-1, HSV-2)

- Lesions: multiple, PAILFUL, vesicular, coalescing. - Many sites: penis, vagina, cervix, anus, vulva. - Lesions may be primary or recurrent. - 60% of patients will experience recurrences. - These lesions are prone to secondary bacterial infections.

Injury by Ionizing radiation - Radiosensitivity of specialized cells? Gy #'s that cause issues? What are the earliest blood cells to be affected by this damage?

- May injure cells directly or Indirectly by generating oxygen free radicals. Radiosensitivity of specialized cells: - Tissues with HIGH mitotic rate and/or rapid turnover are MOST susceptible; LYMPHOCYTES are the earliest blood cells to be affected. - Highest Sensitivity = regularly actively divide = lymphoid, hematopoietic, germ, GI mucosa, rapidly dividing tumor cells. - Intermediate Sensitivity = fibroblasts, endothelial cells, elastic tissue, salivary glands, eye. - Resistant / division ceases after fetal development = bone, cartilage, muscle, CNS, kidney, liver, and most endocrine glands. Morphologic Changes in Ionizing Radiation to: Brain, Skin, Lungs, Lymph Nodes, GI tract, Gonads. see pic w details! Ionizing Radiation Injury (know the numbers) = (a) 50 Gy (5,000 rads) to any one body region => no severe or lethal consequences; possible minor changes. (b) 3Gy to whole body; 20-50% death. (c) 10Gy to whole body; 100% death. Localized Radiation Sequelae = Neoplasia: Myeloid Leukemias and Cancers of Bone, skin, thyroid, lung or breast. -vs- Severe and Generalized: - whole body - nuclear disasters. - severe CNS injury (capillary damage). - GI mucosal denudation. - Acute bone marrow failure.

HSV prevention and treatment know this

- No vaccine and no cure are available. - Antiviral therapy (acyclovir) is prescribed to reduce the severity of symptoms and reduce the duration and frequency of outbreaks. - Daily suppressive therapy = for very frequent and severe outbreaks. RED BOX: Antivirals do not cure herpesvirus infection. They target replicating virus in the mucocutaneous areas. Latent virus does not replicate and cannot be targeted by current antivirals. Notes: There is no vaccine against HSV-1 or HSV-2. Antiviral therapy can reduce the severity and the frequency of outbreaks, but it will not eliminate the virus completely.

HSV and VZV: important to know (recap)

- Primarily cause mucocutaneous eruption: Different locations, transmission routes. - Establish life-long latent infections in neuronal Ganglia: Different locations {TNG, sacral, and dorsal root ganglia}. - Latent herpesviruses often reactivate: HSV frequently, but VZV only once. - No cure; antiviral treatments (both can be managed w Acyclovir) are available; Vaccine only exists against VZV.

Cytomegalovirus (CMV) - how is it transmitted? not on review but prob should know.

- Vertical transmission in utero, during or after birth = CONGENITAL CMV. - Horizontal transmission in SALIVA, breast milk, urine. - 90% of people are ultimately infected. - Asymptomatic in most people. - Serious infections in AIDS patients and transplant recipients. - Reinfections possible.

EBV and CMV: important to know

- Very high percent of seropositive population - Most primary infections asymptomatic - Life-long latent infections - Reactivations are rare; a problem mostly in the immunocompromised - No cure; antiviral treatments are available for CMV

HSV latent infection - where does this occur? are there symptoms, is patient infectious?

- Viral DNA resides in TNG (Trigeminal nerve ganglion) i.e. it's hiding from the immune system. Not infectious! - Virus does not replicate. - No virus detected in the host. - No symptoms.

What do you give a patient if you suspect they were exposed to HIV, versus what to give if diagnosis confirmed they have it (or you accidentally stuck yourself with a needle)?

1) HAART (highly active anti-retroviral therapy) = "treatment is available for HIV" = several inhibitors of DIFFERENT HIV enzymes: Reverse Transcriptase (RT) inhibitors, protease inhibitors, fusion inhibitors, etc = these target dif. stages in viral lifecycle; very effective and prolong clinical latency and increase survival. "Prevention is the best treatment for HIV". 2) HIV Post Exposure Prophylaxis (PEP) = preventative med GIVEN AFTER suspected HIV exposure, it DOES NOT PREVENT HIV, it helps to decrease likelihood of HIV infection from the exposure. - "What to do if accidentally stick yourself with a needle?" = ER, anti-retroviral therapy.

1. HSV Transmission (herpes) 2. HSV entry and spread 3. Stages in HSV infections (summary) know this

1) HSV is transmitted in saliva, tears, genital and other secretions. Transmission requires CLOSE CONTACT. Oral route, genital route. COMMON DISEASES = oral herpes, genital herpes. RARE DISEASES = encephalitis, neonatal herpes. 2) The virus enters the body via mucosal membrane of the ORAL or the UROGENITAL regions. After primary mucosal infection, HSV SPREADS to local neuron endings. Next, virus travels to the craniospinal ganglia. 3) - Acute PRIMARY mucocutaneous infection. - SPREAD to local sensory nerve endings. - LATENCY in the craniospinal ganglia. - REACTIVATION of virus and SPREAD to initial infection site. - RECURRENT cutaneous infection.

IMPORTANT Influenza PROTEINS YOU NEED TO KNOW?

1) RNA Polymerase <- PA + PB1 + PB2 (for genome replication and transcription). 2) Hemagglutinin (HA) - for entry, binds cell receptor (silica acid), fuses envelope with cell membrane. 3) Neuraminidase (NA) for release: cleaves silica acid, helps release visions from cells surface after budding, targeted by current antivirals.

What do viruses need to "initiate" an infection?

1) Sufficient amounts of virions (one isn't enough). 2) TROPISM 3) Local antiviral defenses must be absent to inefficient.

1,2,3) Three most imp properties of viruses? 4) Why do viruses infect cells? (5) What information is encoded in viral genomes? (6) Types of viral genomes?

1) very small 2) infectious, obligate molecular parasites - replicate only within the cells of living hosts: animals, plants, and bacteria (3) are not living organisms - metabolically inert - selfish genetic elements (4) Lack basic elements necessary for growth and replication. The viral genomes are too small to encode all necessary proteins. They have to reply on the host for replication. ALL viruses (no exceptions) need cellular translation machinery. [i.e. No enzymes to produce nucleotides, amino acids, lipids, and carbohydrates; No enzymes to generate chemical energy (ATP); No protein synthesis machinery: ribosomes, tRNAs, etc.; No genes for membrane biogenesis]. (5) Viral genome = information needed to replicate, build and transmit a virus i.e. genes and regulatory signals required for: genome replication, assembly and packaging of genome, spread to other cells and hosts, modulation of host defenses] (6) Viruses are the only known forms of life that (also) have RNA genomes = ds DNA, ss DNA, ds RNA, + RNA, or - RNA; genomes can be linear, circular segmented.

WERNICKE-KORSAKOFF SYNDROME

1. Chronic ALCOHOLISM + Cerebral Dysfunction. 2. Thiamine deficiency-mediated. 3. Often associated with hemorrhagic necrosis of maxillary bodies. 4. Ataxia, confusion, ophthalmoplegia, nystagmus. 5. Memory loss and confabulation. know this list^

Herpes Virus - properties

1. Everywhere 2. Latent, reactivating infection. 3. Painful (whitlow finger, genital herpes, Kaposi's sarc., cold sore, shingles, herpes keratitis (eye), herpes gladiatum (face). 4. Stealthy - almost everyone has been infected with at least 1 herpes virus (test this by presence of Ab's against that virus. If have them, they are seropositive = these ppl may or may not have outbreaks, but will periodically release the virus, infecting others.).

Indications for Antiretrovirals and types of Antiretrovirals for HIV? Goals for ART (list)?

1. Traditional: "the cocktail" in combination, for acute or chronic HIV = highly active antiretroviral therapy (ART)* 2. Post-exposure Prevention (PEP) for = 2a. Ocupational: Needlestick / sharp / blood exposure or mucosal splash 2b. Non-Occupational: mother-infant transmission; sexual exposure (high risk, known positive) 3. Pre-exposure Prevention (PrEP) = for prevention for those with ongoing high risk. Goals for ART: - Reduce HIV related illness and death. - Improve quality of life. - Restore and preserve immune function. = Provide potent sustained HIV control. - Prevent HIV transmission.

Time to Positivity of HIV diagnostic tests know this

15 to 20 days (following infection) = Fourth generation Enzyme-Linked Immunoassay = ism and IgG antibody and p24 antigen. 10 to 15 days = HIV Viral Load Test for RNA.

How are viruses prevented?

= Vaccines/Vaccination {not available against ALL viruses!}. - Immunization can be ACTIVE or PASSIVE - active induces immune resistance; passive introduces products of immune response e.g. antibodies. - Must be safe, efficacious, and practical (must induce immunity in large fraction of population). - Can protect from infection or from disease - immune response is maintained or primed, disease is delayed or symptoms lessened. - VACCINES CAN BE V. HARD TO DESIGN. - Major Categories of Antiviral Vaccines: 1) LIVE ATTENUATED VIRUSES (Reduced virulence = Nasal Flu vaccine (LAIV), Measles Very effective but less safe, also expensive. 2) INACTIVATED VIRUSES: retain immunogenicity but are no longer infectious. Inactivated injectable Flu vaccine, rabies vaccine. Safer but less effective (multiple doses), also expensive 3) COMPONENT/SUBUNIT VACCINES: contain one or more viral proteins but no viral genome. Hepatitis B, HPV. Very safe, cheap and stable, but less effective, hard to design.

Important HIV proteins

= antiviral targets (all of them!). just know that. 1. gp160 (or Env): binds cell receptor (CD4) and coreceptors (CXCR4, CCR5); fuses envelope with the cell membrane during entry. 2. Reverse transcriptase (RT): Generates DNA from a viral RNA template. 3. Integrase: Integrates viral DNA into the host genome. 4. Protease: Cleaves viral polyprotein into functional proteins.

Despite their diversity, viruses have several common characteristics. Which of the following statements describing such common characteristics is CORRECT? All viruses A. are intracellular "parasites" B. are susceptible to detergents C. contain DNA D. contain lipid E. contain RNA

A is answer = ALL viruses require host cells for replication. Detergent susceptible and contain lipid = enveloped viruses ONLY.

Who is at the highest risk of developing a serious disease upon exposure to VZV? A. An infant B. A pregnant woman C. An immunocompromised person D. A person who has previously had chickenpox E. A person vaccinated against VZV know this.

A, B, and C are all correct. Lecture - Epidemiology of Herpes ZOser: - Patients with zoster are INFECTIOUS until blisters heal. - Isolation is not necessary. - Avoid contact with pregnant women, infants, and the immunocompromised (no hospital visits). - Cover blisters and wash hands frequently.

Acute vs. Persistent Viral Infection Types ?

ACUTE = RAPID & SELF-LIMITING infections; SHORT incubation period; RECOVERY or DEATH of host in 2-3 weeks. Example: influence, rhinovirus. PERSISTENT = LONG TERM infections; LONG Incubation period (may start as an acute infection); virions are produced consistently or intermittently; PRIMARY INFECTION IS NOT CLEARED by adaptive immune response: some cleared eventually, others persist for life = either: Smoldering (i.e. Hepatitis B and C), Latent / Reactivating (i.e. Herpesvirus), or Slow (i.e. HIV, Measles SSPE)

Case - what is the diagnosis? A 23yo male patient complained of weakness, nausea, fever, and abdominal pain, and lack of appetite for several days. On exam, patient's skin and eyes were yellow (jaundice). Patient denied any drug addiction. Labs: increased levels of serum aminotransferases, indicative of liver injury. Antibodies to HAV, HBV, or HCV were absent. HBsAg was detected.

Acute HBV infection - HBsAG is key serological marker for active HBV infection... lab tests indicated liver injury. What happens during acute infection = The virus infects liver cells and replicates. In acute infection, HBsAg is the first marker to appear in the blood. Aminotransferases become elevated 3-4 months later. With resolution, HBsAg becomes undetectable (4-6 months), aminotransferases return to normal levels, and the protective anti-HBs IgGs are detected. BUT, if a patient is tested during the HBs window = Diagnosis based on the presence of anti-HBc IgMs.

Adverse effects of Cancer Chemotherapeutic Drugs - Toxic Effects?

Alopecia. Gastrointestinal Erosion/Ulceration. Bone Marrow Failure.

Which one of the following statements concerning meningitis is TRUE? A. Bacteria that cause meningitis are usually unencapsulated (lacking polysaccharide capsule), which facilitates bacteremia. B. Meningitis is often accompanied by fever and stiff neck. C. Meningitis is usually preceded by infection of neurons in the trigeminal ganglia. D. There are no effective antibiotics against bacteria that cause meningitis. E. There are no vaccines to any of the common causes of meningitis.

Answer is B. Meningitis bacteria virulence factors = capsule, pilli, phase and antigenic variation, and LPS {gram -}. Hematogenous spread in blood, not neurons. Antibiotics exist = treatment for meningitis = Stop bacteremia and/or meningitis with antibiotics ASAP. Vaccines exist = prevention of meningitis = Good vaccine made of capsular polysaccharide linked to protein (doesn't cover all serotypes).

Which of the following is the most common late infection in HIV+ patients? A. Candida B. Tuberculosis C. Pneumocystis pneumonia D. VZV / Shingles know this Also, what are early infections in HIV+ patients, and what are the late infections?

Answer: C, all others are early infection OIs. Early OIs: CD4> 200 = (occur in healthy pop., more common in HIV+ before severe immcompr) = 1. TB, 2. Candida / thrush, 3. VZV / shingles, 4. Recurrent bacterial /pneumonia , 5. histoplasmosis, 6. Kaposi's sarcoma. Late OIs: (a) CD4 <200 = 1. Pneumocystis pneumonia, 2. Chronic diarrhea, 3. cryptosporidia. (b) CD4 < 100 = 1. Toxoplasma (seizures), 2. CMV (visual loss), 3. MAC (atypical mycobacterium).

Which one of the following statements concerning Prions is FALSE? A. Prion disease results from a conformational change in a protein, which then acts as a "seed" to convert more of this protein to the abnormal conformation leading to amyloid fiber formation. B. Prions are believed to be infectious proteins, and do not contain a nucleic acid genome. C. Prions can cause neurodegenerative diseases (for example, Kuru or Creutzfeldt-Jakob disease [CJD]). D. Transmission of prions occurs when bacteria that contain prion proteins are ingested.

Answer: D. prions are infectious proteins, they don't get transmitted.

Arboviruses (3/16 ID) - examples? rare diseases it can cause? wasn't in review.

Arthropod-BOrne Viruses - most single stranded RNA, enveloped. - E.g. Yellow Fever Virus, Dengue Virus, Eastern Equine Encephalitis Virus (EEE), WEST NILE VIRUS, Zika Virus Acute Encephalitis - Brain {CNS location}. WEST NILE VIRUS = (mosquito, bird, middle of USA, summer months) - Highest incidence in Middle USA and Summer months. - Mechanisms: bites you => makes proteins in saliva that keep blood vessel open so can drink blood, but virus actually goes into your secretions and into cells in skin and can multiply and when it gets into stuff like DC's (dendritic cells) aka immune system lymph fluid s.t. it'll be allowed to move around and can cross into blood stream and can infect many dif cells. And once in blood stream (like N. meningitis), can cross blood-brain barrier. It can cross into the NERVE TISSUE: Neuroinvasive diseases = rare, but death rate is high.

Ascaris Lumbricoides aka Roundworm (Metazoa) - how transmitted and understand transmission risks. know this.

Ascaris Lumbricoides = Roundworm, Metazoa. = > 1 billion cases globally, most prev in tropical and subtropical regions and areas with bad sanitation, more in children. Principle Host: Humans. Habitat: Small Intestine. Infective form: Ova (Eggs). Transmission: Fecal-Oral, ingestion of embryonate ova (eggs). Most infections are Asymptomatic. But can cause stunted growth in children. Rarely obstructed intestine or biliary tract. Respiratory symptoms during migration of larvae through the lungs: cough, Dyspnoea, hemoptysis, eosinophilic pneumonitis. [see picture - intestinal obstruction due to Ascaris lumbricoides, in infant].

Which of the following statements about Influenza is FALSE? A. Influenza envelope bears two important viral antigens. B. Influenza virus is a double-stranded DNA virus. C. Migratory aquatic birds serve as reservoirs of Type A Influenza virus. D. Only H1-H3/N1-N2 influenza viruses are capable of sustained transmission among humans and causing pandemics.

B is answer its segmented RNA. Type A = birds. On slide: "Only H1-H3/N1-N2 viruses are capable of sustained transmission among humans and causing pandemics" - since Type A is the type that's divided further into subtypes and those that can be in humans = w. H1, H2, H3 subtypes and N1, N2 subtypes {know this, bold}.

Which of the following statements about HIV is FALSE? A. Clinical latency stage can last 15 years or more. B. HIV can be transmitted in saliva and tears. C. Reverse transcriptase is a viral enzyme that can be targeted with antivirals. D. The decline in immunity due to destruction of CD4+ T cells leads to AIDS. E. A very high risk of HIV transmission is associated with the transfusion of infected blood.

B is answer. ACUTE STAGE 3-4 WEEKS. CLINICAL LATENCY can last >10 years! ANTIVIRALS target: RT, Integrase, Protease, & GP160 {<= "imp. HIV proteins"} HIV Transmitted = 1. blood 2. genital secretions 3. Mother-To-Child (breast milk, pregnancy, birth).

Which of the following is the most common target of HIV drugs? A. Fusion/entry inhibitors B. Reverse transcriptase inhibitors C. Protease inhibitors D. Integrase inhibitiors

B is answer. Antiretroviral Drug Classes (know): 1. Nucleoside (and nucleotide): Reverse Transcriptase Inhibitors 2. Non-Nucleoside Reverse Transcriptase Inhibitors 3. Protease Inhibitors 4. HIV entry inhibitors -Fusion Inhibitors -CCR5 Inhibitors 5. Integrase inhibitors

Which one of the following statements concerning the human gastrointestinal (GI) tract and GI tract infections is TRUE? A. Bacteria, but not viruses, are causes of diarrhea. B. Diarrheal infections in the large intestine usually result in bloody (dysentery) diarrhea while infections in the small intestine usually lead to watery (secretory) diarrhea. C. Enterotoxigenic E. coli (ETEC) and Vibrio cholerae both produce an AB toxin that stops translation in host cells by inhibiting the ribosomes. D. The mucosal surfaces in the GI tract, respiratory tract, and genitourinary tract are topologically interior. E. The normal flora (microbiota) is sparse in the oral cavity and large intestine.

B is answer. Bacteria and viruses both cause diarrhea. ETEC AB Toxin (Shiga toxin) does do that; but Vibrio Cholerae's AB toxin doesn't. GI tract is TOPOLOGICALLY EXTERIOR. Normal microbiota is opposite of sparse in oral cavity and large intestine.

In HIV+ patients with low CD4 counts, primary prevention of Mycobacterium avium complex (MAC) is achieved with a weekly dose of: A. Clarithromycin B. Azithromycin C. Trimethoprim/Sulfa D. Penicillin Also, what is used primary prevention of Pneumocytosis in HIV+ patients with low CD4 counts? know this

B is answer. PREVENTION of HIV: [Primary prevention is prevention of first occurrence; secondary is to prevent recurrence in someone previously treated for HIV] - Primary Prevention of Pneumocystis (risk when CD4 < 200 or 250) w. Trimethoprim/Sulfa. - Primary Prevention of MAC (risk when CD4 < 74), with Azithromycin weekly dose. note: MAC = Mycobacteria Avian Complex (non-tuberculosis mycobacterium species present in soil and water)

Which of the following statements regarding Respiratory Syncytial Virus (RSV) is FALSE? A. No vaccine against RSV is currently available. B. RSV infections in adults cause laryngotracheobronchitis, also known as croup. C. In infants, RSV infections can cause life-threatening swelling and buildup of mucus in the bronchioles. D. Rapid diagnosis of RSV infections in newborns is essential for successful treatment. E. Passive immunization can be used to prevent infections in at-risk neonates.

B is answer. RSV in adults cause upper respiratory infections. In children cause laryngotracheobronchitis (croup, barking cough). In infants cause bronchiolitis.

Statement 1: The rate of new cases of HIV in the US is decreasing every year due to treatment success and public health efforts. Statement 2: More than 50% of new cases of HIV globally are under the age of 24.​ A. Statement 1 is true, statement 2 is false B. Statement 2 is true, statement 1 is false C. Both statements are true D. Both statements are false know this

B is answer. USA HIV: - More than 1 million ppl = CLIMBING # due to treatment success; steady number of new cases despite public health efforts; aging population of men and women (defy stereotype). - New cases (2015) 39,513 per year (19% decline in new cases 2005 -14) = Male >> female (3:1 ratio); MSM > Hetero >> IDU; & AA > White > Latino. Global HIV: - In 2009, 33 million with HIV = 22 mil in sS Africa, 4 mil in asia. - 1.8m deaths/year = 2/3 in sSA. - 2.5 mil children with HIV, accounting for 90% of AIDS deaths in sSA. - 2.6 mil NEW CASES per year = 97% in low+middle income countries; 51% in women; 41% age 15-24 & 16% children <15 yr.

Epstein-Barr Virus (EBV) is NOT associated with A. Burkitt's lymphoma. B. Chronic hepatitis. C. Infectious Mononucleosis. D. Nasopharyngeal carcinoma. E. Oral hairy leukoplakia.

B is answer. EBV CAN CAUSE HEPATITIS, BUT DOESNT CAUSE CHRONIC HEPATITIS.

Which of the following statements about protozoa is FALSE? A. Although they are unicellular, protozoa can exist in multiple developmental stages. B. Protozoa are prokaryotes and their infections can be treated with antibiotics. C. Protozoa are single-celled, microscopic organisms that can perform all the necessary functions of metabolism and reproduction. D. Some species of protozoa are part of the normal human microbiota while others can cause disease.

B. protozoa are eukaryotes. Protozoa = single cell, with one or more developmental stages (intracellular, extracellular), - have either simple or complex life cycles {in one or more hosts or in environment: human, animal, vector}. - They PERFORM ALL FUNCTIONS of the organism i.e. of metabolism and reproduction {= can be free-living or parasitic, and can multiply in humans}; - have cellular grade of organization; - microscopic; - no gonads, no larval stage, no pelicle. - 4 types Transmission: Oral, Sexual, Vectorborne; or Blood Transfusion. - 3 types Multiplication/Replication: Asexual {all protozoa reproduce asexually: binary fission or multiple fission}, Sexual in definitive host (i.e. plasmodium in mosquitoes), or Both (i.e. cryptosporidium). - Are classified based on Movement. Metazoa (larger) = Helminths = multicellular; dif. cells or organs perform dif. functions; have cellular tissue, organ and system grade of organization; can be seen by naked eye (not microscopic); gonads present, larval stages present; and pellicle present = free living or parasitic in nature (similarity).

Concentrations of glucose, neutrophils, proteins, pressure in the cerebrospinal fluid (CSF) for bacterial meningitis, viral meningitis, fungal meningitis? know

Bacterial = most neutrophils; decreased glucose {Bacteria metabolize glucose so that's why glucose is lower, but viruses don't care about it}; increased proteins, and very elevated pressure. Viral = less neutrophils (most lymphocytes), normal glucose, inc. proteins, slight inc. pressure. Fungal = same neutrophils as viral (most lymphocytes), decreased glucose and inc. proteins (same as bacterial), and mod. elevated pressure.

An adult person was vaccinated with the HBV vaccine using three doses and standard vaccination procedures. To determine if the vaccination was successful, 2 months after the last vaccine dose, a test was performed to measure the titer of anti-HBsAg (HBV surface antigen) antibodies present in the blood. Surprisingly, although no anti-HBsAg antibodies were detected, anti-HBcAg antibodies were found. Which scenario best explains this observation? A. The person had no exposure to HBV prior to or subsequent to vaccination, however, the vaccination failed to illicit a protective response. B. The person had an acute HBV infection prior to vaccination and the infection has since resolved (that is, the person is no longer infected). C. The person had a chronic HBV infection prior to vaccination. D. The person acquired a chronic HBV infection from the vaccination (vaccine-associated hepatitis).

C is answer. A is wrong because - a. No exposure to HBV = no anti-hbc. B is wrong because - acute then resolved = both anti-Hbs and anti0HBc. D is wrong bc vaccinated person would have Hbs but not Hbc. [vaccination doesn't contain replicating virus, so obviously they couldn't have gotten a chronic infection from it].

Which of the following statements about the epidemiology of influenza is FALSE? A. The trivalent influenza vaccine generally consists of two Type A strains and one Type B strain. B. Health-care workers are at increased risk of acquiring influenza infection and, if infected, may transmit virus to their patients. C. Influenza pandemics occur at regular and predictable intervals. D. Influenza virus is spread from person to person by respiratory droplets or by contact with objects recently contaminated with nasopharyngeal secretions.

C is answer. Pandemics are IRREGULAR, 10-50 year intervals.

Which of the following statements about Varicella-Zoster Virus is FALSE? A. Causes a vesicular rash B. Patients with shingles can be infectious C. Recurrent episodes of symptoms result in gradual destruction of CD4+ T cells. D. Remains latent in sensory ganglia following primary infection E. Responds to antiviral therapy

C is answer. Nothing to do with immune, latency between outbreaks is in neurons.

Acute poisoning characterized by cherry red color of the skin and oral mucosa is due to? know this

Carbon Monoxide

Common Cold Viruses - know disease and epidemiology Common colds account for __(#) of all ____ (type of infection) in humans. Majority of cases caused by? Differentiate diseases caused by Adenovirus, Coronavirus, Rhinovirus. know this

Common colds account for ONE-THIRD TO ONE-HALF OF ALL ACUTE RESPIRATORY INFECTIONS in humans. Symptoms: rhinitis, sneezing, coughing, sore throat. Complications: secondary bacterial infections Causes - symptoms between are indistinguishable: - 40-50% cases due to RHINOVIRUSES = MOST! - 10-30% cases from coronaviruses. - Rest % from adenoviruses, RSV, and parainfluenza viruses. RHINOVIRUSES = Picornavirus family, +ssRNA, non-enveloped = transmitted via aerosols/secretions/formites/winter months => complications include sinusitis, otitis media, asthmatic bronchitis; has >100 serotypes so vaccine is unlikely. CORONAVIRUS = Coronavirus family, +ssRNA, enveloped = Seropositivity >90% in adults; Up to 30% common colds. - EMERGING CORONAVIRUSES: 2003: Sudden Acute Respiratory Syndrome (SARS) in China. & Since 2012: Middle Eastern Respiratory Syndrome (MERS). ADENOVIRUSES = Adenovirus family, dsDNA, non-enveloped = ACUTE PNEUMONIA (in military recruits), Respiratory: common cold, pharyngitis, cough; Gastroenteritis, or diarrhea (in children); "Pink eye" (from swimming pools); and Disseminated infections in transplant patients. TREATMENT: SELF-RESOLVING; Prevention with live,attenuated vaccine (discontinued).

Which statement best describes five human Hepatitis viruses? A. They are blood-borne. B. They belong to the same viral family. C. They cause chronic infections. D. They cause liver disease.

D is answer.

Each of the following organisms is correctly paired with its usual environmental reservoir EXCEPT: A. Ascaris and contaminated soil. B. Cholera and contaminated water. C. Giardia and contaminated water. D. Plasmodium and contaminated soil. E. Schistosomes and snails.

D is answer. Plasmodium (malaria) in mosquitos.

Hypothermia - direct vs. Indirect effects?

Direct Effects = Physical disruption of cells. Indirect effects = circulatory changes, atrophy, and fibrosis.

Mechanical Trauma (injury by physical Agents)

Due to (know list): - Abrasions. - Contusions. - Lacerations. - Incised Wounds. - Puncture Wounds. May produce damage by: - cutting, tearing, or crushing tissues. - severe blood loss. - interruption of blood or air supply. E.g. Bone & Tendon => Fracture: (know list) - closed or compound. - may bleed into adjacent muscle, other tissues. Causes of Death (know list): - Hemorrhage into body cavities. - Fat embolism from bone fractures. - Ruptured viscera - Secondary infection. - Renal failure.

Which one of the following statements concerning the central nervous system (CNS) is FALSE? A. Encephalitis means infection of the brain. B. Meningitis means infection of the meninges. C. The CNS is a well-protected space and thus infections are rare relative to other sites in the body. D. The concentration of glucose in the cerebrospinal fluid (CSF) is lower than normal for bacterial meningitis, whereas it is normal for viral meningitis. E. The hematogenous route of CNS infection refers to infection emanating from the nerves.

E is answer.

Which one of the following statements about Herpes simplex virus (HSV) infections is TRUE? A. HSV-1 primarily causes a sexually transmitted disease whereas HSV-2 infections primarily localize to the perioral region and are spread by kissing. B. Frequent hand washing can help reduce the spread of HSV. C. Herpetic Whitlow is an infection of the nose or ear lobes and requires slightly cooler than body temperature to manifest. D. HSV produces an AB subunit toxin, which destroys nerve cells. E. Antiviral drugs can reduce the severity and duration of HSV reactivations.

E is answer. 1 is mostly cold sores, 2 is mostly genital sores. Herpetic Whitlow is fingers. Frequent hand washing would help because spread is via oral or genital.

CNS infection (terminology) at these CNS locations? know this. 1. Brain 2. Spinal Column 3. Meninges

Encephalitis - Brain Myelitis - Spinal Column Meningitis - Meninges

Reye Syndrome know this

Encephalopathy following acute, febrile, viral illness in child. Almost ALWAYS in association with aspirin use - Chronic Aspirin Toxicity.

Parvovirus B19 - know disease and epidemiology What disease does it cause? When is a person contagious / when not? Typical symptoms? know this

Erythema infectuosum (Fifth disease). First, minor respiratory symptoms (cold-like) => A few days later, a typical rash may itch, lasts ~1 week = "slapped cheeks" and red,lacy rash of trunk/extremities. Mainly affects 4-10 yo Highly contagious prior to rash. NOT CONTAGIOUS ONCE RASH APPEARS {rash is due to the reaction of the immune system to the virus}. 50% immune by adulthood

True or false: Recurrent oral herpes occurs in more than 50% of orally infected individuals.

FALSE! - 45% of orally infected individuals experience reactivation. - Frequency of recurrences varies between individuals. - Prodrome of tingling, warmth or itching at the site. - ~12 hours later, redness followed by papules and vesicles. - Diagnosis is based on clinical symptoms. - Acyclovir to speed up recovery [Cold sores or herpes labialis result from reactivation of an HSV-1 or an HSV-2 infection. The outbreak is typically preceded by a tingling feeling called prodrome. Cold sores are the most common manifestations of an HSV infection.]

1. True or False: there are more new cases in White people in USA with HIV than latinos. 2. True or False: Globally, the majority of HIV cases are in asia. 3. True or False: More than a quarter of the global deaths due to HIV occurred in sSA. 4. True or False: 90% of deaths in sSA due to HIV were in adults. 5. True or False: Globally, the majority of new HIV cases per year are in low and middle income countries. fix star

False - USA New cases (2015) 39,513 per year (19% decline in new cases 2005 -14) = Male >> female (3:1 ratio); MSM > Hetero >> IDU; & AA > White > Latino. 2. False - Global HIV: - In 2009, 33 million with HIV = 22 mil in sS Africa, 4 mil in asia. 3. True.Global: 1.8m deaths/year = 2/3 in sSA. 4. False. Global: - 2.5 mil children with HIV, accounting for 90% of AIDS deaths in sSA. 5. True. Global: - 2.6 mil NEW CASES per year = 97% in low+middle income countries; 51% in women; 41% age 15-24 & 16% children <15 yr.

Health Effects of Climate Change - Global Temp and Sea Levels by 2100?

Global temperature projected to rise 2-5 deg C by year 2100. Sea levels expected to rise 2-6 feet by year 2100.

Staphylococcus Aureus - illness (case in class)? 1. How you decipher it from other staph human pathogens, and what illnesses do they cause? 2. How decipher it from strep? 3. How it gets into you? 4. How it survives in you? 5. What damage it does, how to treat it, prevention? wasn't in review.

Gram-Positive Cocci - Illnesses: Abscess formation (brain abscess case below), Toxin Production, Meningitis, Food poisoning, Sinusitis, Invasive Diseases. 1. Don't confuse w. other staphylococcal human pathogens: do a Coagulase (clots serum fibrinogen) and Protein A antigen test: positive always means aureus, below show negative results. (a) Staph Epidermis -> medical device-related infections (b) Staph Saprophyticus -> Urinary Tract Infection. 2. Don't confuse with Streptococcus: do a Catalase test: negative result means strep, positive result means staph. 3. How S. Aureus (pos. catalase, pos. coagulase tests) gets in: trauma, surgery, med. procedures breaching skin/mucous membranes -> skin, nares, GI {entry from nasal or oral cavity sinuses causes aprox. 25% of chronic sinus infections} -> enter into deeper tissues . 4. How S. Aureus survives in us (virulence factors): Inhibits Phagocytosis {capsule, coagulase}, Adhesins {tissue colonization}, Battery of secreted proteins {for creation of hospitable extracellular milieu; proteases, Dnases, Lipases); and Toxins {interfere w. immune response}. 4. What Damage it does, how to treat it, how to prevent it: - Spectrum of acute and chronic infections. - Antibiotic Therapy = Methicillin, Vancomycin. Problem of multiple antibiotic resistant S. aureus "Superbug" {e.g. methicillin resistant s. aureus [MRSA]}. - No vaccine. Case (Brain Abscess): Recurrent Ear ache, new symptoms of headache + nausea + blind spot in right eye; low-grade fever; CT scan w large mass consistent w abscess; Neurosurgeon does needle aspiration of abscess and it showed Gram-Positive Cocci; Cultures grew S. aureus; Tx w. IV antibiotics to kill the staph and other anaerobes pos. present in the abscess -> abscess shrank, complete recovery except blind spot remained in eye.

HBV, HCV, HIV and you (the dentist) prob should know this.

HBV - increased risk in dentistry! = Bloody dental procedures; Greater among oral surgeons and periodontists. HCV - accidental puncture with a needle is the most common transmission, 2% risk. HIV - accidental puncture with a needle is the most common transmission, 0.3% risk Thus: - Prevention is best (gloves, masks, etc.). - Follow safe injection practices. - Get vaccinated against HBV. - Advise patients *NOT to share toothbrushes, razors, nail clippers.*

HBV vs HCV (overview, check your understanding) 1. Transmission? 2. Of those infected, majority recover or get chronic? 3. Is vaccine, PEP, antivirals available?

HBV is transmitted thru genital fluids or blood-to-blood. Usually people recover (90-95% recovery with long-lasting immunity). Vaccine exists, and PEP is used. HCV is transmitted primarily blood-to-blood. Usually people get Chronic Hepatitis (80%; other 20% recover though). No vaccine and No PEP, but effective antivirals available.

Hepatitis B (HBV) and Hepatitis C (HCV) - is there more acute disease than chronic disease in which?

HBV: acute < chronic (5%). HCV: acute > chronic (80%).

PEP - when is it effective? optimal duration? know this

HIV -> start PEP SOON! - PEP most effective if implemented ASAP. - animal studies suggest PEP probably not effective when started OVER 36 hours after exposure, but interval in which there is NO benefit from PEP is unknown. a) 100% receiving PEP (tenofovir) within 24 hours after IV SIV infection remained uninfected. b) 50% protection if given at 48 hours. c) 25% protection if given at 72 hours. - "Consider" PEP if Over 26 hours. - Optimal Duration = 28 days of PEP! a) if given PEP for 28 days, 100% protection. b) for 10 days, 50% protection. c) for 3 days, 0 protection.

HIV, HBV, HCV - what are the stages of each infection? and how do you diagnose each at different stages? (objectives) know this

HIV STAGES: 1. Initial Infection = symptoms (fever, lymphadenopathy, pharyngitis, rash, aches, malaise) last 1-4 weeks. 2. Clinical Latency Stage CAN LAST 15 YRS OR MORE = asymptomatic; CD4 destruction. - Note: this stage is prolonged by HAART (highly active anti-retroviral therapy) which inc. survival of HIV patient (is HIV prevention/tx). 3. AIDS = can take many years to develop = high HIV-RNA, low CD4 counts (<200, CMI lost); weight loss & waisting; opportunistic infections {bacteria, virus, fungi, protozoa; e.g. Candidiasis (ORAL thrush), Oral Hairy Leukoplakia, Kaposi's Sarcoma of mouth}, Tumors, Neurological disorders. HIV DIAGNOSIS: - Acute Stage: viral RNA levels. - 3-4 weeks later: detection of anti-HIV antibodies. HBV STAGES: 1. Acute Hep B = hepatomegaly, nausea, fever, jaundice; rarely death. 2/3 of ppl infected with hep B get symptoms. 2. Chronic = chronic liver inflammation; eventually, liver cirrhosis or hepatocellular carcinoma = Only 5% of ppl infected with hepB get chronic (most recover w. immunity). "HBV is an example of an oncogenic virus" 3. Fulminant Hepatitis {Rare, less than 1% of ppl infected get this} = massive hepatic necrosis, high mortality. HBV DIAGNOSIS [HBsAg is marker of active infection; Anti-HBs antibody is marker of immunity]. 1. Acute HBV - HBsAg (first marker to appear in the blood). - No Anti-HBs IgGs (antibodies) - Yes Anti-HBc antibodies = in window at 3-4 months after exposure to HBV, IgM. *imp: this diagnosis (based on presence of anti-HBc IgM's) is used if patient is tested at 3-4months post exposure*. 2. Resolved HBV - HBsAg seroconversion from HBsAg to anti-HBs IgG. - No HBsAg - Yes Anti-HBs IgGs (antibodies. - Yes Anti-HBc Antibodies = IgG. 3. Chronic HBV - HBsAg present for >6 months; no anti-HBs IgG. - Yes HBsAg - No Anti-HBs IgGs (antibodies. - Yes Anti-HBc antibodies = IgM. 4. Vaccinated - No HBsAg - Yes Anti-HBs IgGs (antibodies). - NO anti-HBc antibodies. HEPATITIC C (HCV) STAGES: 1. Acute HCV - asymptomatic (60-70%), and so is v. hard to diagnose. 2. Chronic HCV - slowly progressing, CIRRHOSIS, Hepatocellular carcinoma = 80% (majority, differ from HBV) of people infected get its {only 20% recover with immunity}. HVC Diagnosis: - Positive anti-HCV antibody test does NOT distinguish resolved vs. chronic infections -> need to test for HCV RNA - To distinguish acute vs chronic infection: check in 3-4 months for HCV RNA!! 1. Acute HCV: - Yes HCV RNA - High Aminotransferases levels - Early on, NO anti-HCV antibodies; but later on, YES "". 2. Chronic HCV (most cases): - Yes HCV RNA - Variable aminofransferases levels - Yes anti-HCV antibodies. 3. Resolved (less likely): - No HCV RNA. - Normal Aminotransferases levels. - YES anti-HCV antibodies.

HIV, HBV, HCV - how are each transmitted, what are the transmission risks? (objectives) know this

HIV Transmitted = 1. blood (NEEDLESTICK, open wound, blood TRANSFUSION of INFECTED BLOOD, solid-organ transplants, healthcare workers) 2. genital secretions (sexual, mucous membranes) 3. Mother-To-Child (breast milk, pregnancy, birth). HBV Transmitted [Hepatitis B, liver disease] = 1. blood 2. Bodily fluids / genital secretions [e.g. Sex, birth, transfusion/dialysis/transplantatoiin, IV drug use, sharing razors or toothbrushes {NOT saliva, but blood}, Needlesticks.] HCV Transmitted [hepatitis C, liver disease] = 1. Blood [e.g. Transfusion, dialysis, transplantation; IV drug use; Needlesticks; Birth; Sharing razors or toothbrushes (some risk); Sex (low risk)].

HSV-1 vs HSV-2 know this

HSV1 - [HSV-1 more commonly @ mouth (spread by oral route, in saliva, and is typically acquired at a very young age) Less commonly @ penis (It can also, but less frequently, be spread through sexual contact and is then acquired in early adulthood)]. - 1. Cold sores, sore throat, fever, and, rarely, encephalitis = Age 0-5 = Spread through saliva (oral route). - 2. Less frequently genital infection = Young adults = Spread by sexual contact (oral-genital route). - BOLD: HSV-1 is found in 95% of oral sores and 40% of genital sores. HSV2 - 1. Usually genital sores = Young adults = Spread by sexual contact (genital route) - 2. Less frequently cold sores = Young adults = Spread by sexual contact (oral-genital route). - BOLD: HSV-2 is found in 5% of oral sores and 60% of genital sores

Virion - definition? Structure? know

Infectious unit of virus. Structure includes: (1) Nucleic acid that can be DNA or RNA, not both. (2) Capsid [protein shell] protects the nucleic acid from environment, bears viral attachment and penetration proteins in *non-enveloped* viruses; Sensitive to BLEACH = symmetric because of genetic economy (caspid is build using same type molecule over and over) -> viral capsid proteins have structural properties that permit "regular and repetitive" interactions among them -> protein capsids of most viruses display ICOSAHEDRAL or HELICAL symmetric, except poxviruses have COMPLEX symmetry. (2a) Capsids w Icosahedral Symmetry = 20 triangular faces make up icosahedron; 12 vertices; closed shell an be built w as few as 60 identical subunits; final particle looks spherical. (2c) Helical Symmetry = RNA viruses only; stacking repeated components. (2c) Complex Symmetry = Pox Viruses (Fowlpox). (3) Envelope [lipid] protection, bears viral attachment and penetration proteins in *enveloped* viruses, sensitive to DETERGENT and BLEACH. - note: "nucleocapsid" = nucleic acid + capsid (protein shell).

Influenza - shape of virus/genome? location, types A and B, subtypes, differences between two mechanism of antigenic variation, vaccination? know this

Influenza Virus = ENVELOPED, -ssRNA, family orthomyxovirus (straight, mucus) = SEGMENTED genome (8 dif segments; most segments code for 1 protein (HA, NA, etc.), segmentation allows for random assortment in mixed infections). Entry: UPPER AND LOWER RESPIRATORY TRACT (respiratory route). Symptoms: fever, chills, headache, sore throat, general malaise - Often, severe acute disease Encounter: inhalation of droplets, touching fomites (virus survives for several hours on surfaces)- More efficient transmission at low temperature and low humidity (winters). Incubation period: 1-3 days - Adults with flu are infectious for 1 day before and 5-7 days after the onset of symptoms - Children - over a week Outcome: full recovery, in most cases. Typically, <0.1% mortality rate. Complications: secondary bacterial infections (bc virus causes extensive tissue inflame and necrosis in respiratory tract enabling easier colonization by bacteria), pneumonia. Can be fatal in elderly, infants. To Detect: RAPID INFLUENZA DIAGNOSTIC TESTING (RIDT) detection of influenza antigen from nasopharyngeal swabs by immunoassays that can identify the presence of influenza antigens TO CONFIRM: Viral culture and isolation; RT-PCR. Prevention = good hygienic practices (recall one can get infected by touching infected surface and then touching nose), and disinfection (virus survives several hours on surface); or Vaccination with Inactivated Virus Vaccine. Treatment = since flu is self-resolving disease, doesn't need to be treated with antivirals. But antivirals R a GOOD choice for ppl at risk of serious flu complications (e.g. children under age 2, adults over 65, pregnant women);; are administered within 2 days of symptoms; all of them block neuraminidase [NA] (virion release)= e.g. Oseltamivir (Tamil), Zanamivir (Relenza), Peramivir (Rapivab). VACCINATION: = because of the ANTIGENIC DRIFT (strains of influenza of variation). Based on STRAINS FROM THE END OF LAST YEAR's FLU SEASON. = INACTIVATED INFLUENZA VACCINE: for HEALTHCARE WORKERS, individuals at risk severe infection... everyone over 6 months can get it (formaldehyde-treated virus; given injection; 60-90% effective in healthy adults). = TRIVALENT VACCINE WITH two type A's and one Type B strain (2016-2017), or QUADRIVALENT VACCINE with two type A's and two type B's. Type B = infect mainly humans, only epidemics (drift). Type A = Infects BIRDS, many mammals, and humans; Epidemics (antigenic drift) AND PANDEMICS (shift); Severe disease possible; Migratory aquatic birds are the RESERVOIR {<= avian reservoirs of influenza subject to rearrangement: New influenza A viruses constantly emerge from migratory aquatic birds and spread to mammals, including humans. In birds, influenza replicates in the gut and is excreted into water in large quantities: Nonpathogenic in wild birds; Pathogenic in chickens. Very complex life cycle}. = Type a is FURTHER DIVIDED INTO SUBTYPES (w. antigenically different HA and NA surface proteins): HUMANS w. H1, H2, H3 subtypes and N1, N2 subtypes {know this, bold}. TYPE A (SUBTYPES) AND B ARE FURTHER DIVIDED INTO: STRAINS - variation due to antigenic drift, used in naming.

Acetaminophen (tylenol) know this

Large doses lead to hepatic necrosis (liver). Toxicity begins with nausea, vomiting, diarrhea. Used in suicide attempts, often in United Kingdom.

Risk of Transmission (overview) - which route has highest risk (for HBV, HCV, HIV)? know this

Percutaneous >>> risk of transmission, than intact skin or mucous membrane exposures. Estimated risk of transmission from percutaneous exposure to blood through needle punctures or other injuries caused by contaminated sharp objects: - HBV 1%-30% risk. - HCV 1.8% - 3% risk. - HIV 0.3% risk.

Neisseria Meningitidis - 1. how does it get into you? 2. VIRULENCE FACTORS (know these) 3. What damage does it do to your body? 4. "disease" outcomes? 5. Treatment? 6. Prevention?

Meninges (CNS location) - Acute Meningitis {other bacteria can cause this tho} Cause: gram neg diplococci: 1. How you get it: inhalation respiratory droplets, saliva exchange -> colonizes nasopharynx {nasopharyngeal microbiota (normal flora)} -> spread to bloodstream -> crosses blood-brain barrier. 2. How it survives in you (virulence factors): CAPSULE (serum resistance, anti-phagocytosis, is polysaccharide), PILLI (attachment to host cells), Phase and Antigenic Variation (avoid immune response, reversible on/off switching of pilus), LPS (inflammatory toxin, only find in gram-neg's outer membrane) 3. What "damage" it does:Septicemia, Meningitis, Spotted Fever, Purport Fulminans (shock, rapidly fatal) blue/black fingertips. 4. Outcomes: Nasopharyngeal Carriage; Bacteremia and Meningitis. 5. Treatment: stop bacteremia and/or meningitis with antibiotics ASAP. 6. Prevention: good vaccine made of capsular polysaccharide linked protein {doesn't cover all serotypes}. Peak incidence at 6-24 months / 1 y.o. {age related immunity to N.M.} Emergency: YES! (If dentist notice symptoms (vomited earlier, headache, stiff neck, bright dental light bothering), send the patient to ER immediately!)

Electrical injury - mortality vs morbidity?

Mortality (death) = current passing through brain or heart. Morbidity ("disease")= cessation of activity in cardiorespiratory brain centers; cardiac arrest and arrhythmias; small cutaneous burns with blister (vesicle, bulla) formation - point of entry or exit of the electric current.

Important Hepatitis B Virus (HBV) proteins (not on objectives)

Note - HBV = enveloped, ds/ssDNA virus. It infects and replicates in liver cells. 1. Hepatitis B surface antigen (HBsAg) = Key serological MARKER of active HBV infection, elicits protective antibodies. 2. Hepatitis B core antigen (HBcAg) elicits antibodies.

Other Manifestations of HSV - Ocular herpes and Herpetic Whitlow know this - where they are

Other less common manifestations are Ocular herpes and Herpetic Whitlow, which frequently affects medical professionals if they don't wear gloves. Herpetic Whitlow - acute infection of fingers; doctors, nurses (HSV-1 and HSV-2) Ocular herpes - broad spectrum of ocular diseases (HSV-1). see pic!

What is a parasite? What is a host? What is a vector? know definitions

Parasite = Organism that lives on or in a host organism and gets its food from or at the expense of the host. Commonly refers to: eukaryotic pathogens, protozoans and helminths = "Ectoparasite" lives on surface of host, or "Endoparasite" lives inside the host. Host = "definitive host" w. parasite that reproduces sexually; or "intermediate host" that is required for parasite development, but this parasite doesn't reach sexual maturity. Vector = organism (usu. arthropod) that transmits the parasite.

Respiratory Syncytial Virus (RSV) - know epidemiology and diseases. know this

RSV IS SEVERE IN INFANTS. RAPID DIAGNOSIS AND TREATMENT IS KEY. OXYGEN TENT. Paramyxovirus family, -ssRNA, enveloped Major cause of childhood disease. aerosols/secretions/formites, winter months, very common -> Respiratory DISEASE (adults: URIs; children: laryngotracheobronchitis (croup or barking cough)). DAMAGE caused by both RSV and the host immune response. (1a) RSV in Infants = BRONCHIOLITIS {swelling and mucus buildup in the bronchioles. w. Symptoms i.e. Tachypnea (rapid breathing), wheezing, lung hyperinflation, cyanosis, fever}. High-risk infants: premature, pulmonary disease, congenital heart disease, immunocompromised. - Diagnosis of RSV in infants = RAPID antigen test on nasopharyngeal aspirates; - Treatment "" : Oxygen tent, IV fluids; - Prevention in "" : PASSIVE IMMUNIZATION with palivizumab in high-risk infants; No vaccine, yet.

Radiation induced mucositis.

Radiation induced mucositis.

Heroin - Sequelae of this addictive opioid?

Sequelae of this addictive opioid derived from poppy plant: (know list) - sudden death (usu from overdose). - pulmonary & renal diseases - infections: HIV, hepatitis B, infective endocarditis. - skin lesions

Vibrio Cholerae - (1) how does it get in and what does it do in your body? (2) treatment once you're infected?

Small Bowel Pathogen (comma shaped) Causing secretory diarrhea. (1) Environment, Oral ingestion {infectious dose is high, but decreased by achlorhydria (low Hcl in stomach)} -> mucus of small bowel and adheres to epithelium via adhesin proteins -> spreads extracellularly {extracellular pathogen} and multiplies extensively => AB TOXIN A1-B5 subunit cholera toxin = alpha subunit of toxin crosses membrane of intestinal cell and permanently activates G protein -> the G protein activates adenyl cyclase enzyme, which then starts to produce cAMP 2nd messenger -> high cAMP activates channel in membrane -> EFFLUX of IONS and WATER (follows) from infected enterocytes, leading to watery diarrhea. - Note on toxins: "some bacteria cause serious disease w/o entering into deep tissues of the body BC toxins that act a distance." (3) Rehydration THERAPY is necessary and sufficient. Case: blood group O, takes H2 blockers for ulcer disease, just got back from South American country and next morning had semi-solid stool, many large watery stoosl, vomited a lot. Went to ER: he was afebrile (NO FEVER) w. slightly elevated pulse and decrease blood pressure; complained muscle cramps and dizziness. Watery Stool contained lots of highly motile Comma shaped bacteria -> given 3 liters fluid IV, then placed on oral rehydration solution. Culture grew Vibrio cholerae, so he was given oral tetracycline to shorten course of infection -> 4 hours after starting tetracycline his diarrhea stopped and he recovered rapidly and completely.

Coxsackie A virus - know disease and epidemiology. know this

TWO COMMON INFECTIONS DENTISTS SEE: (causes two mild diseases, typically in children) = Herpangina & Hand, Foot, and Mouth Disease - Spread by fecal-oral route and respiratory droplets - Summer and early fall HERPANGINA = white papules with red base on posterior palate and pharynx (back of mouth_ . + Fever, sore throat; infants and young children; duration 3-4 days. HAND, FOOT AND MOUTH DISEASE = low-grade fever, headache; children, and more rarely, adults; duration 7-10 days.

Carcinogens in cigarrets? know this.

Tar, Polycyclic aromatic hydrocarbons, and Nitrosamines.

Is a person with shingles infectious? A. Yes B. No What disease would result from exposure to a person with shingles? A. Shingles B. Chickenpox know this.

Yes - a person with shingles is infectious. Blisters filled with fluid have high viral titers, they are very itchy / scratch / open up. VZV can be transmitted by respiratory route (to uninfected people). They would develop Chickenpox. Primary infection the disease is going to be chickenpox. Only get shingles from latency infection and then virus has reactivated.

Risk factors for oral/oropharyngeal squamous cell carcinoma include

Traditional risk factors incl. tobacco and heavy alcohol consumption. Others include HPV, h/o cancer, immunosuppression. know this fact!

HSV-1 recurrent infection

Upon reactivation (STRESS!), virus replicates and travels down sensory nerve fiber to infect epithelial cells. Free virus is released with or without clinical symptoms. Other triggers include: Stress, sunlight, immunosuppression, chemotherapy, infection, etc..

A-B Toxin's mechanisms of action

Vibrio Cholerae's AB cholera toxin -> turns on G Protein permanently => watery diarrhea. Shiga Toxin (AB) in STEC (e.coli) => inactivates ribosome and stops translation in host cell -> damage lg bowel epithelium -> bloody diarrhea.

Entamoeba Histolytica - how transmitted and understand transmission risks know this

[Protozoa] (1) Entamoeba Histolytica = one host is human. Two stages: trophozoite and cyst. One form replication is binary fission; Movement via PSEUDOPODIA. (2) Prevalent worldwide, higher inc. in developing countries. In industrialized countries risk groups include male homosexuals, travelers, recent immigrants, and institutionalized populations. (3) Transmitted by fecal oral route, contaminated food or water, person to person. (4) Wide clinical spectrum from Asymptomatic {=luminal, E. despar, non-pathogenic}, Diarrhea, Dysentery {invasive}, liver or lung or brain abscess {extra intestinal}. Incubation period 2-4 weeks (when symptoms appear).

Giardiasis - how transmitted and understand transmission risks? know

[Protozoa] (1) Giardia = Two stages = Trophozoite and Cyst. One form replication is Binary Fission; Movement via FLAGELLAE. (2) Prevalent worldwide, more common warm climates and in children. Transmitted by fecal oral route, contaminated food or water, person-to-person, animal-to-person. (3) Either asymptomatic infection or with severe diarrhea and malabsorption. - Acute form develops after incubation period of 1 to 14 days (avg 7 days) and usu. lasts 1 to 3 weeks. - Symptoms = diarrhea, abdominal pain, bloating, nausea, vomitting. - Chronic has recurrent symptoms + malabsorption and debilitation may occur.

Protozoas in the oral cavity? For each: Infection found in patients with? Transmission via? Diagnosis and treatment? know this.

[Protozoa] (1) Trichomonas Tenax = commensal of human oropharynx; found in patients w. poor oral hygiene and advanced periodontal disease = transmitted by direct contact aka kissing = can rarely cause empyema or peritonitis, esp. in immunocompromised hosts = FLAGELLAE. (2) Entamoeba Gingivalis = considered non-pathogenic, found in 85% of patients w. gum disease and 50% ppl w healthy gums; live in oral cavity in gingival pocket near base of teeth; transmitted from person to person orally by formites (e.g. eating utensils) or kissing; worldwide distribution = only trophozoites, no cyst stage; feed on bacteria and other debris = diagnosis via trophozoites in scrapping from gums and teeth [should be distinguished from E. Histolytica trophozoites which may be found in sputum from pulmonary abscess] => no treatment bc its considered non-pathogenic = pseudopodia is mobile element.

Cryptosporidium spp. C. Parfum, C. Hominis - how transmitted and understand transmission risks know this.

[Protozoa] One or more hosts. Several stages = extracellular [oosts, sporozoites, merozoites, microgametes] and intracellular [trophozoite, meront, gammon, zygote]. Two forms of replication = Asexual [schizogony, merogony] and Sexual [gametogony]. Movement via gliding motility of zoites. Prevalent worldwide, more common low and middle income countries (LMIC) - causing mod. to sev. diarrhea in young children, and inc. risk of death in toddlers. Transmitted by fecal oral route, infected water and food, person to person and animal to person. MAJOR CAUSE of Waterborne outbreaks. - Asymptomatic or self-limited infection in "immunocompetent hosts" BUT can be severe, chronic and ultimately fatal in "immunocompromised ppl" such as untreated HIV/AIDS patients (i.e. becomes opportunistic pathogen). - Watery diarrhea, dehydration, weight loss, abdominal pain, fever, nausea, vomiting; incubation period 2-10 days, lasts 1-2 weeks, can be chronic.

Trichomonas Vaginalis - how is it transmitted? transmission risks?

[Protozoa] Trichomonas Vaginalis - accounting for aprox. 7.4 million cases/year. One host = human. - Prevalence: worldwide, higher in people with multiple sexual partners or other venereal disease {STD}. - Transmitted Sexually. - Women infection is freq. symptomatic - vaginitis with purulent discharge is the prominent symptom, can be accompanied by vulvar and cervical lesions, abdominal pain, dysuria and dyspareunia. Incubation period is 5 to 28 days. - Men infection asymptomatic; occasionally get arthritics, epididymitis, and prostates.

Toxoplasma Gondii (Toxoplasmosis) - how transmitted and understand transmission risks know this

[Protozoa] Definitive Host: Cat. Intermediate Hosts: Rodents, Birds, Pigs, Sheep, Humans. Several Stages: Extracellular [oocysts, sporozoites] and intracellular [tachyzoites, bradyzoites]. Two forms replication: Asexual [Endodyogyny] and Sexual. Movement: gliding motility of zoites. Prevalent worldwide, one of the most COMMON INFECTIONS. Transmitted by eating undercooked meat of animals harboring tissue cysts, cat-feces contaminated food or water, litter box, blood transfusion or transplacentally from mother to fetus. Immunocompetent (host) gen. asymptomatic infection or flu-like illness (only in 10-20%). AIDS (immunocompromised host) patients w. TOXOPLASMIC ENCEPHALITIS due to reactivation of brain cysts => ocular toxoplasmosis, or congenital toxoplasmosis.

Plasmodium spp. (malaria) - how transmitted and know transmission risks

[Protozoa] Definitive Host: Mosquito. Intermediate Hosts: Humans. Several Stages: Mosquito [gametocyts, gametes; ookineetes, oocysts, sporozoites] and Human [sporozoites, schizonts, trophozoites, merozoites, gametocytes]. Two forms replication: Asexual [schizogony, sporogony] and Sexual [gametogony]. Movement: gliding motility of zoites Prevalent int tropical areas, sub-saharan africa, asia. Transmitted by bite of infected female Anopheles mosquito (vector-borne). Clinical presentation varies depending on the species and level of parasitemia. Generally fever and chills, headache, myalgia (muscle pain), arthralgia (joint pain), weakness, vomitting, and diarrhea. P. falciparum causes most severe disease = "Cerebral Malaria," acute renal failure, severe anemia, or acute respiratory distress syndrome.

Varicella-zoster virus (VZV) know this

[This herpesvirus causes two diseases: chickenpox in children and shingles in older adults. Chickenpox is a primary infection. Shingles, however, are the result of reactivation, so one cannot develop shingles without having chickenpox, *with one important exception*.] "The virus that strikes twice" 1. Varicella (chickenpox) = Children (mostly); Primary infection. 2. Herpes zoster (shingles) = Older adults who have had chickenpox; Recurrent infection later in life. VZV entry and spread = VZV is the ONLY human herpesvirus TRANSMITTED BY RESPIRATORY ROUTE. - Respiratory entry -> Spread to lymphoid system and the blood (viremia) -> Spread to skin (VESICULAR RASH) -> Finally, spread to other organs, such as sensory neurons. - Disease not at the entry site but after spread. 1. Disease #1: Varicella (or chickenpox) = THE RESULT OF A PRIMARY INFECTION WITH VZW = > 1a. Highly infectious; Contracted from another infected individual, usually a child; Systemic infection resulting in a generalized, VESICULAR RASH; Mild but many complications: Staph infections, meningitis. 1b. Varicella diagnosis and management: - Clinical diagnosis: fever, lymphadenopathy, and a widespread vesicular rash. - Varicella is self-limited = no treatment! - Disease is more severe in adults. - Recovery results in life-long immunity [repeated infections are rare]. - LATENT INFECTION {REMAINS LATENT IN SENSORY GANGLIA FOLLOWING PRIMARY INFECTION}. 2. Severe Varicella: 2a. Varicella in the immunocompromised - More severe disease in children undergoing treatment for cancers such as leukemia and lymphoma. - Life-threatening complications such as disseminated varicella, pneumonia, and encephalitis are much more likely. - ANTIVIRALS, passive vaccination ARE NECESSARY. 2b. Congenital varicella - Severe birth defects; fortunately, very rare 3. Varicella vaccine (ACTIVE immunization) 3a. = VARIVAX (live attenuated vaccine) since 1995; Strain Oka Children, at 12-15 months then 4-6 yo; Single dose, 95% seroconversion; In US, part of routine vaccination; Drastic decrease of Varicella in the US; Breakthrough Varicella (15-30% cases) is less severe in the vaccinated. .......BUT...... The live attenuated virus used in the vaccine becomes LATENT -> The vaccinated persons still get shingles (even if less frequently)! 4. Varicella vaccine (PASIVE immunization) = VariZIG (Zoster immunoglobulin), passive immunization for urgent protection, <96 hr after exposure; Persons at risk of severe disease and complications e.g. Pregnant women, Newborns of infected mothers, Premature infants, Immunocompromised. 2. Disease #2: Herpes Zoster (Shingles) - In 10 - 20% of individuals, a SINGLE RECURRENT INFECTION infection occurs after several decades, over the age ~50y. - Infections are UNILATERAL, painful vesicular blisters, usually in the head or upper trunk. - The rash erupts along one of the many nerve paths, called dermatomes, that stem from the spine. *Blisters filled with fluid containing high viral titer* 2a. Herpes Zoster: recurrent VZV infection - Following primary infection, VZV establishes latency in the DORSAL ROOT GANGLIA: Viral DNA resides in the dorsal root ganglia; No replication, no virus or viral proteins produced; Asymptomatic infection. - Years later, virus REACTIVATES: Replicates in the ganglia; Travels down the sensory nerve fiber; Infects epithelial cells innervated by the nerve. - Clinical: a unilateral rash. - In the immunocompetent: a single reactivation with advancing age (decline in acquired immunity). - In the immunocompromised: multiple earlier reactivations. 2b. Herpes zoster diagnosis and treatment: - CLINICAL diagnosis is usually sufficient - very typical unilateral distribution - LABORATORY confirmation - often only for atypical presentations, e.g., in the immunocompromised [PCR to detect VZV DNA in vesicle fluid]. - Antiviral therapy (Acyclovir), pain medication (manage shingles). 2c. Herpes Zoster vaccine: - Zostavax (high doze of Varivax, 14X); 60% reduction in the number of cases; Recommended for everyone >60yo, repeat every 5-8 years; Given to boost the immune system; Not necessary for those who had shingles (shingles are a better boost)

Helminths - transmitted and understand transmission risks

[metazoa] (1) Development and Multiplication: Sexual Reproduction: in definitive (human) host, for most nematodes. Parthenogenesis: production of offspring without fertilization by the male, for strongyloides {no parasitic male}. Hermaphroditism: male and female organelles in same helminth, for all trematodes (flukes) except Schistosomes. (2) Transmission (2a) Oral - ingestion of embryonated eggs in food or formites [for Ascaris, Trichuris]. - ingestion of larvae in undercooked meat [for trichenella]. - ingestion of trematode cercariae in seafood [not Schistosomes]. (2b) Percutaneous - penetration of skin [for ankylostoma (hookworm) larvae; Schistosome cercariae]. (2c) Bite by Arthropods [for Filaria (mosquito)]. (3) Mechanisms of Pathogenesis: - Mechanical {obstruction by worms e.g. Ascaris; or anemia due to hookworm infections}, - Competition for Nutrients, or - Immune Inflammatory {induce Th2 responses which may pre-dispose to other infections; induce secretion of eicasanoids which down regulate inflammatory pathways; dying helminths induce host mediated immunopathology aka tissue destruction w. onchocerciasis, cysticercosis}. (4) Intestinal Helminths = Nematodes (Roundworms), Cestodes (Tapeworms), and Trematodes (Flukes).

Schistosoma (Trematode, Fluke): S. Mansoni, S. hematobium, S. japonicumm - how transmitted and know transmission risk? Environment they are in?

[metazoa]. Principle Host: Humans, Intermediate host: SNALS (Biomphalaria). Habitat: Portal circulation in liver, mesenteric venues of bowel, venous plexus of bladder. Infective form: Cercariae. Transmission: Transcutaneous, skin penetrated by cercariae in fresh water. 3 dif species found in Dif. Locations: S. Mansoni in Caribbean, Africa, Middle East. S. Haematobium in Africa and Middle East. S. japoncium in far east. Many infections Asymptomatic. But Acute infection [Katayama's fever] (by S. Mansoni and S. Japonicum) w. fever, cough, abdominal pain, diarrhea, hepatosplenomegally, and eosinophilia. Continuing infection may cause granulomatous runs and fibrosis in the affected organs, colonic polyposis w blood diarrhea (S. mansoni); - portal hypertension w. hematemesis and splenomegaly (S. mansoni, S. japonicum); - cystitis and urethritis (s. haematobium) w. hematuria, which can progress to bladder cancer; - pulmonary hypertension (S. mansoni, S. Japonicum, more rarely S. haematobium); glomerulonephritis; and central nervous system lesions. Picture (super swollen belly): "Hepatic scarring due to presence of Schistosomes (S. mansoni) in the liver leads to obstruction of blood flow and build up of fluid in the abdominal facility.

E. Coli (1) How does it get into us and what damage does it cause? (2) Why is E.coli "sometimes" a pathogen?

flora, small bowel pathogen, and large bowel pathogen. (1) undercooked meat products from processing plants-animals infected. vegetables; parsley, lettuce (human or animal feces contaminated); cider => colonization in large intestine; directly attaches to intestinal epithelium {colonization by bacteria is localized...} => {...but damage is systemic} 1. Watery Diarrhea, 2. Bloody Diarrhea, 3. Hemolytic Uremic Syndrome (HUS). (2) E.coli is "sometimes a pathogen". - Some strains have virulence factors that cause damage to intestine or other organs e.g. (A) Toxins {STEC = Shiga Toxin (an A-B toxin) + E. Coli, & ETEC = Enterotoxigenic E. Coli} (B) factors promoting adherence to host cells, (C) factors promoting entry into epithelial layer of gut. - Some strains have virulence factors that allow extra intestinal colonization e.g. (a) urinary tract infections {url-pathogenic E. Coli [UPEC]}: pilli. (b) Meningitis: polysaccharide capsule {antiphagocytic}. - AKA ETEC [E.Coli, heat-labile toxin; enteroxigenic E. Coli) cause watery diarrhea in small bowel [turning on G protein and efflux salt and water from cell; similar mech to cholera toxin]. VS STEC [shiga-toxin producing E.Coli] cause bloody diarrhea by blocking ribosomal translation and damaging lg. bowel wall. Case: "Can red meat kill you": Invasive, Shiga toxin-producing E. Coli in contaminated, undercooked meat => large bowel infection, kidney failure due to toxin.

Define Viral Tropism know this.

preference for infecting specific cell types/ tissues or organs - cells as the entry site must be: ACCESSIBLE {virus can reach the cell}, SUSCEPTIBLE {virus can penetrate cell}, and PERMISSIVE {virus can replicate inside the cell}. "accessibility, susceptibility, permissibility, and the availability of the antiviral defenses of the host." Example 1: Hepatitis B virus (HBV) infects and replicates only in liver cells (liver-specific enhancer); transmitted by blood (to access liver) Example 2: Influenza uses ubiquitous sialic acid as a receptor but infects and replicates in human respiratory tract (virus needs specific protease produced there). However, some mutant strains can infect liver, lungs, etc. Example 3: Herpes Simplex virus (HSV) infects and replicates in epithelial cells and neurons (neurotropic) but is really pantropic - disseminated disease in the immunocompromised

Herpes Simplex encephalitis (HSE)

severe HSV infection (1 of 3) - Most serious complication of herpes: ~70% mortality without treatment; 20-30% mortality with treatment; <3% return to normal function. - Clinical: fever, headache, mental status changes, seizures. - Characteristic hemorrhagic necrosis of temporal lobes (MRI image) - Luckily, rare: 2 in 250,000 in the US. - Typically, due to reactivation. - Most common viral encephalitis. - THE ONLY treatable viral encephalitis - order *MRI and Lumbar Puncture* HSE diagnosis and treatment: - MRI = characteristic hemorrhagic necrosis of temporal lobes (edema and abnormal signal) - Cerebrospinal fluid (CSF) tap: PCR confirmed the presence of HSV-1 DNA; Cerebrospinal fluid tap = more lymphocytes than neutrophils. - Treatment: Intravenous acyclovir as soon as HSE is suspected. Patient was treated with intravenous acyclovir for four weeks and oral valacyclovir for an additional three weeks => Outcome: Patient required long-term speech therapy but returned to fully independent living. Case: A 57 yo patient was admitted with a 3-day history of mental status change. Patient complained of confusion, mild frontal headache. No significant previous medical history and no recent illnesses. On exam: normal vitals, mild dysnomia on questioning. Over the next day, increasing aphasia (language impairment) => MRI and a lumbar puncture ordered.

Neonatal herpes

severe herpes infection (2/3) - 1 in 4000 live births in the U.S. - 90% acquired AT DELIVERY. - SYMPTOMS = 1) Mild disease SEM (skin, eye & mouth) - Easiest to diagnose, best outcome. 2) Encephalitis is severe - the brain may be liquefied; <10% mortality if treated but high morbidity. 3) Disseminated disease - Worst prognosis, 40% mortality; Diagnosis difficult - may resemble bacterial sepsis. - TREATMENT: acyclovir in all suspected cases. - PREVENTION: offer caesarean section to mothers with genital HSV lesions.

Disseminated herpes in the immunocompromised

severe herpes infection (3/3). - HSV disease is more frequent and severe in Patients receiving: cytotoxic therapy, organ graft recipients, AIDS patients. - SEVERE LOCAL DISEASE OR DISSEMINATED INFECTION may be seen. - ACYCLOVIR is used to treat HSV infection -> resistance to acyclovir may emerge during long term therapy. - ACYCLOVIR IS NOW ROUTINELY GIVEN AS PROPHYLAXIS IN TRANSPLANT PATIENTS.