Micro Final

1918 pandemic

1918-1919, H1Ni subtype, 20-100 million people. WW1 combat deaths 9.2 million. .5% of US population died. >500,000 deaths, 43,000 in army Life expectancy dropped from 51 to 39 years in 1919. Disproportionate mortality among infants and young adults. Killed many between 25-34 yo, very uncommon for most flu strains. Usually just 0-4 and 65+ (combined flu and pneumonia mortality). Genome isolated from exhumed bodies, but still no thorough understanding of hyper virulence.

Hepatitis C

1989 discovered. Previous existence presumed because some hep patients not positive for A or B, before discovery called non-A non B HV. Flavivirus with dengue, yellow fever, other viruses. ssRNA genome, enveloped. Human liver only. Continual destruction of HCV infected hepatocytes by cell mediated immunity. Same clinical manifestations as HBV including small % develop cancer. 25% of infected clear infection and never develop disease. Transmission. 60% drug use, 15% sexual, 10% transfusion before screening. DiagnosisL serum antibody against HCV capsid, does not distinguish between present and past infection. If antibody test positive, RT PCR to test for HCV genome as marker of current infection. Treat: drug combination (direct acting antiviral agents DAAs drugs that target HCV nonstructural proteins including protease and polymerase of HCV). Vaccination against HBV and HAV. PRevent: reduce reservoir not feasible: requires widespread screening tests with RT PCR confirmation and treatment with DAAs potential side effects and drug drug interactions, likely to have low compliance. Best approach: intercepting transmission: continuation of generally excellent blood screening in blood banks. Reduce incidence among injection drug users. Education about risk of sexual transmission. Meticulous attention to preventing contamination in medical facilities with equipment shared between patients (dialysis).Common in Egypt, Bolivia, Mongolia, Cameroon >10%. Rest of world generally 1-3%. Egypt: Aswan Dam 1970, schistosomiasis, injected therapy, HCV. Vaccine problems: mutates frequently, 6 different strains and antibodies to one doesn't work for others. No good animal models, hard to test vaccine. Currently: envelope protein as target and virus like particles as preparation. Currently in Phase 1/2 stage of safety and side effects. 175 million infected

Emerging disease

AIDS, MDR TB, Dengue, Hanta HPS, Lyma, Ebola, Leptospirosis, Cholera in Americas Adenovirus 14, Human monkepox, WNV, chikungunya, Flue strains, yellow fever, Marburg hemorrhagic, SARS, Hendra, Nipah, Enterovirus. Key factor: international trade/travel, economic development and land use, deforestation/reforestation, new roads, mines, plantations. Ecological and climate change, behavioral and demographic change, technology and industry, microbial adaptation, breakdown of public health. Population growth. Microbial genetic adaptation and change, polymicrobial disease, human susceptibility, intent to harm, occupational exposure, imappropriate antibiotic use, lack of public health, animal population, war and famine, lack of political will. Physical environmental, social political economic, genetic and biological, ecological, microbe and virus, human and animal. Control: Identify, communicate, diagnose, new approach to vaccine and therapeutic design. Move from agent only in animals, to primary infection only from animals, to limited outbreak from animals or a few cycles of humans, long outbreak from animals or many cycles of humans, or exclusive human agent only from humans.

Hansen's disease. Leprosy. Mycobacterium leprae.

Acid fast bacteria, first discovered by Norwegian Hansen. Human reservoir. Carried in nose and disseminated to skin. Mode of transmission not clear, skin to skin contact or nose to skin. Difficult to determine because incubation is 3-20 years. Grows only at 35C, can't grow at 37C. Lesions mostly on face, hands, feet. No invasions to internal organs, no one ever dies. Obligate intracellular parasite. Multiplies within epidermal cells, phagocytic cells, and peripheral nerve cells and destroys. Destruction of nerve cells causes anesthesia (lack of feeling) which leads to accidental injury of fingers and toes. Genetic susceptibility important host factor. Tuberuloid: 80%, scaling and discoloration of skin, anesthesia in center of lesion. Less severe, cell mediated immune good and usually leads to recovery. Puffiness of ear rim. Nodular, Lepromatous: 20%, disfigurement of facial features, disappearance of fingers and toes, clawed hands and feet, blindness. More severe, inadequate cell mediated immune, although response to other microbes normal. Spots all over. Skin necrosis. Fewer fingers. Big bumps, especially on face. Claw hands can be treated surgically in earlier stages, preventing crippling. Loss of bone tissue. Diagnosis: signs. Lesions, anesthesia in lesions. Lab: Tissue biopsy with acid fast bacteria within cells. PCR. Can't be cultured on any medium. Treat: Dapsone first and most important drug since 1940. Rifampicin and clofazimine now been added since Dapsone resistance developed. Prevention: forced isolation in leper colonies in medieval times. In 1800 and first half of 1900s, forced isolation in leprosariums. Damien de Veuster ministered in Molokai Hawaii hospital. US public health hospital Carville, LA. Leprosy museam Bergen Norway. In one year, few lesions to basically entire face, and arms and hands have lesions. By mid 1900s, apparent not highly communicable. Most people genetically resistant. Therapeutic drugs developed. Treated patients don't shed bacteria. Reduce reservoir through treatment. Could lead to global eradication. About 200 cases per year in US. 20-40 new cases annually from armadillo transmission. Up to .15% of population in South America, Africa, South Asia.

Tetanus. Clostridium tetani.

Anaerobic gram positive bacillus. Reservoir: ubiquitous in soil globally. Multiplies in animal and plant matter that is decaying so O2 was metabolically consumed. Spores form under adverse conditions (oxygen) and retain bacteria in living but inactive form. Transmission: soil contaminated deep wound, not communicable between people. Potent exotoxin. Produced only when multiplying, not in spore form. Toxin fixes to nerves ennervating muscles and prevents normal relaxation of muscle after it has contracted. Only skeletal muscle affected. Diagnose: based on signs and symptoms. First sign lockjaw (trismus) tight clenching of jaw muscles. Extreme arching of back, everything tight. Involuntary contractions last severely minutes and are extremely painful. Patient may die from choking or suffocation. Neonatal tetanus from infection of umbilical cord with soil contaminated instrument. Mortality 10-60%. Toxin very immunogenic. Theoretically would elicit strong response. So potent that amount necessary to cause disease is too small to be immunogenic. Treatment: immediate passive immunization with anti-tetanus toxin antibodies produced in human volunteers hyperimmunized with the vaccine. Neutralizes toxin immediately. Prevent: toxoid vaccine from inactivated toxin. Part of routine childhood vaccination DTap, boosters every 10 years. 100% effective. Was never super common. 29 cases from 1996 to 2009. Occurred in unvaccinated people or those who hadn't gotten appropriate boosters. Now mostly in Africa and Asia, rest of developed world eliminated.

Random Covid stuff

Antibody kinetics: too early to characterize how antibodies will change. Recent studies: seroconversion median: igM 12 days, igG 14 days, neutralizing antibodies 11 days. Long term studies COV 1 and hCoV: IgG waned over time, typically detectable up to 1-3 years, only partial protection against reinfection. Recent study: dynamics of Cov2 specific antibodies similar to Cov1. Memory B cells to Cov1 decreased 90% 2-8 months after infection and were not detected 6 years after. Memory T robustly maintained. Cases varying severity: develop detectable antibodies against human CoV, including Cov1 and 2. MERS CoV: seroconversion rate and peak antibody levels increase with disease severity. Low or no seroconversion in asymptomatic or mild. Covid: As in MERs and Cov1, titer increases with disease severity. Severity appears to be associated with time to detection of igG (2-3 days longer for more severe cases), no data available for asymptomatic. Recent study: elevated serum IgM levels indicate poor outcome in patients with COVID pneumonia. Genetics: Coronavirinae subfamily of coronaviridae family, 4 distinct genera. Alpha: HCoV229E and NL63. Beta: A HCoV OC43 and HKU1. B SARS CoV 1+2. C MERS CoV and multiple bats. D: Only bats. Sequence homology of Cov1+2 76% of S and 90% of N. Antibody cross reactivity: within alpha and beta, but minimal reactivity between. Infections with endemic HCoV rarely induce cross reactivity to SARS 1 and MERS. Emerging HCoV can induce cross reactive binding antibodies towards endemic and other emerging. Evidence for antigenic evolution in receptor binding domain of emerging. RBD in S1 very specific for SARS 2. Vaccine options: live attenuated, whole inactivated, virus like, recombinant subunit, DNA/RNA, synthetic peptide, recombinant bacterial vector, recombinant viral vector. S protein good target from SARS1 and MERS. Most protein subunit based, mostly spike or receptor binding domain. Then Viral vector, then nucleic acid. Could: test if polio or TB vaccines could fight through general immune response rather than specific adaptive, or whether certain immune could be modified to target virus. Fastest a vaccine has ever been developed is 5 years. Preclinical trials, 1 safety and dose selection 40, 2 small group efficacy 100s, 3 large group efficacy 1000s, licensing, monitoring and mass vaccination. Goal for COVID is under 18 months. Preclinical trails same time as safety and dose selection trails, single safety and efficacy trial, emergency licensing. Preclinical: test antigen, test adjuvant, use animal model of mouse ferret rhesus, use info from other related virus, GMP process development. 05/08 99 candidates, 5 phase 1, 6 phase 2 (mostly China). Modified antigen presenting cell, viral vector, inactivated, RNA based (German/US), DNA based (US), Protein subunit, DNA based spike (Canada). 05/28 20 days later, 138 candidates, 1 phase 4 (TB and MMR vaccine), 2 phase 3 (weakened cold virus with spike protein, modified APC), 7 phase 2, 5 phase 1. US mRNA 1273 Moderna NIAID. RNA based, phase 1 45. Lipid nanoparticle LNP dispersion with mRNA encoding for prefusion stabilized spike protein. Host cells take up mRNA, generate protein, display to immune system, generate immune response against spike protein. US INO 4800 Inovio. Electroporation of DNA plasmid encoding S protein. Phase 1 40;. ds DNA plasmid that encodes S protein. Intradermal delivery. Small electric pulse forms small pores in cells, easier uptake. Cells create spike proteins, trigger T cell and B cell antibody response. Ad5 nCoV CanSino Biologics Canada China DNA based Phase 2 508. Spike into unreplicating Adenovirus, injected intramuscularly. PiCoVacc: Sinovac Biotech: Phase 1/2 144 and 600. Inactivated. Covid 19/aAPC Shenzhen Geno Immune Medical Institute. Modified APC Phase 1 100. Artificial APCs transformed with lentiviral vector to present COVs antigen. Inactivate cells. Multiple subcutaneous injection. Prime T lymphocyte.

Viral Systemic

Arbovirus: Dengue fever, breakbone, mosquito. Tropics and subtropics. Yellow fever, mosquito. Filovirus fevers Bunyavirus fevers Arenavirus fevers Colorado tick fever Parvovirus infection Coxsackievirus infection

Varicella Zoster Virus

Chickenpox. Varicella zoster virus Generalized macular (discolored) skin lesions. Primary infection. Red spots. Highly contagious, generally benign, self limiting. Shingles. Varicella zoster virus. Pain and skin lesions, usually on trunk. Adults with diminished immunity. Susceptible children exposed to shingles can get chickenpox. Latency in ganglia, shingles reactivation. Painful red rash. 1 million people, over 65. 1/3 of chickenpox people reactivate from dorsal root ganglia, transport to skin. Only in people who previously had chickenpox. Rash develops into clear blisters (full of infectious virus), moderate to severe pain. Potentially dangerous to elderly. Nerve damage results in post herpetic neuralgia PHN. Only suffer once. Hemorrhagic varicella: classic cases on chickenpox in newborn. Severe skin infections on face and neck. Dark red splotches. Enter mucosal surfaces, Waldeyer's ring, infect T cells, transmitted by infected T cells 1st viremia. Amplified in internal organs, especially lungs, spleen, liver. 2nd viremia, infect skin causing chickenpox, infect sensory ganglia and establish latent infection, reactivation, infect skin dermatome causing shingles or post herpetic neuralgia PHN. Disease burden developed: incidence 1.6%/year. Complication 3% of time. Hospitalized 0.5% and deaths 0.3% of cases. Global minimum estimate of disease burden: 140 million cases, 4.2 million complications, 4.2 million hospitalizations, 4200 deaths. Mostly in kids. >90% of cases, 70% of hospitalizations, 50% of deaths. Treat: difficult to prevent transmission. 1995 vaccine. Live attenuated virus (Oka Merck strain from guinea pig embryo fibroblasts). Routine vaccination 12-18 months. PRotects 90-95%. Immune disease or pregnant shouldn't get. May increase shingles risk. Shingles up to 1M/year in US. Merck shingles vaccine Zostavax reduced incidence, severity, and duration of shingles 60%. GSK shingles vaccine Shingrix subunit gE approved in 2017.

Covid treatment

Cholorquine and Hydroxychloroquine. Widely used antimalarial and antiinflammatory drugs. Controversial due to lack of solid clinical data. Results promising in cell cultures, but failed to be seen in humans. Can cause cardiac problems. Clinical trials to evaluate at different stages. Several stopped early from adverse events with the third dose. Blocks pH acidification of endosome/lysosome, blocks fusion. Remdesivir prominent candidate, high efficacy against all coronaviruses and robust clinical safety (Ebola virus trial). Compassionate use showed improvement. Multiple randomized control trials showed it shortened hospital stays from 15-11 days (30%), need to administer early. No serious side effects. Binds to RNA dependent RNA polymerase, stops replication. Convalescent plasma: transfer immunity, transfusion of plasma from recovered Covid 19 patients to severely ill. Pilot study in 10 severely ill patients (China) revealed transfusion well tolerated and in 7/10 patients, viral load undetectable 1 week later. Difficult to achieve consistent levels of antibody with different transfusions. Antibodies of recovered person wane very quickly so must be collected quite soon after infection resolves. Block binding to receptor. Signal Fc receptor on phagocytes to eat.

Mycobacterium Tuberculosis

Consumption White plague. Evidence from Egypt 3000 yo and earlier. Massive global health problem, 1/3 of world infected, 3 million deaths/year, 10 million new cases. Transmission: airborne, inhalation of droplet nuclei (1-5 micron) or respiratory secretions, into pulmonary alveoli. Occurrence worldwide: incidence peaked 2005-06, stable, decreasing in some areas, in parts of Africa 1%, in US, about 1/10,000, incubation 2-10 weeks. Reservoir: primarily human, rarely other primate. M bovis cattle and other mammals. Symptoms: Cough, fatigue, fever, night sweats, weight loss, pleuritic pain, cough initially unproductive purulent (pus) bloody. Pathogenesis: Inhalation of droplet nuclei, neutrophils - multiply. Macrophage, lymphocyte recruited. Alveolar macrophages (phagocytize tubercle bacilli, multiply, survive). No toxins. Acute cell mediated inflammatory response. Tissue necrosis. Chronic granulomas (tubercles). 90% of infected don't develop active disease (but immunocompromised 5-10% of year). Primary disease: CMI response may contribute to tissue destruction if bacterial proliferation not controlled. Disease manifestation depends on bacterial proliferation, dissemination, and CMI response. Latent TB: doesn't transmit disease, immune response controls infection, but doesn't clear bacteria. Reactivation: disease occurs from proliferation of bacteria already in lungs, disease >2 years after new infection. Deterioration in host immune function (HIV/AIDS), diabetes, cancer chemotherapy, old age. Cloudy lungs surrounding hole. Darker lungs with holes. Clinical: Iceberg, most exposed not infected (70%), most infected no disease (60%), reactivation of latent 2-23% in lifetime, 5-10% per year with AIDS. Genetics, nutritional status (malnourished), immunocompromised plays role. Some may form granulomas and control disease that way. Granuloma stays with people for life. Bacteria sometimes escape and cause disease, reactivation. Host: susceptibility: immunodeficiency, age, AIDs, anti inflammatory drugs, young kids, elderly. More if impoverished, malnourished, disadvantaged, minority, urban. Immune response: cell mediated immunity, failure to respond: milliary TB spread by circulatory to organs (small lesions, millet seeds). Diagnosis: Acid fast stain, rapid molecular testing, culture and ID, biochemical, DNA testing. Anti-microbial resistance testing (when needed). Skin test - PPD purified protein derivative, induration, previous exposure and immune response. In vitro interferon gamma release assays, measure release of IFN gamma by T lymphocytes stimulated with TB specific antigens. Chest X ray. Treatment: WHO 2 months daily doses, Isoniazid (INH), Rifampin, Pyrazinamide, Ethambutol. Multi drug (combination) therapy important to prevent resistance. Latent: 6-9 months of isoniazid alone. Muti Drug Resistance MDR resistant to INH and RIF (at least). Extensively resistant XDR MDR+ resistant to second line drugs, 2005 outbreak in KwaZulu Natal SA, 52/53 patients died, median survival after diagnosis 16 days.

diphtheria

Corynebacterium diphtheriae (bacteria), gram positive bacillus. Epidemiology: reservoir is human, respiratory, incubation 2-7 days Pathogenesis: potent exotoxin coded for by bacteriophage integrated into bacterial DNA. Kills human cells by interfering with protein synthesis of cell. Symptoms: somewhat red throat, pseudomembrane (Dead cells and leukocytes make white back of throat), bull thickened neck, possibly leading to obstruction of airways, low grade fever under 102, respiratory paralysis could cause death. Pain, shortness of breath. Diagnosis: Symptoms, Bipolar gram positive staining, sent to public health lab, growth on Tellurite medium (tellurium #52 element inhibits growth of endogenous microbes) Less than 5 cases/year. Formerly important disease causing significant morbidity and mortality. 1900, #10 killer of all causes in US. Before toxoid vaccine in 1940s, 1/20 in temperate zones had diphtheria in life and 5-10% of cases led to death. 30-50% mortality (mostly by suffocation) in kids under 4. Sequelae: myocarditis, polyneuritis, significant cardiac abnormalities in 20% of patients. Treatment: Host antibodies not fast enough to survive disease, fatality rate 20-50%. Passive immunity with anti-toxin serum (from horses) administered quickly. Penicillin or Erythromycin also helps prevent carrier state. Supportive care to enable breathing (tracheotomy). Prevent: DTP (diphtheria, tetanus, pertussis) vaccine, toxoid, immunity induced by toxin protects against toxin mediated systemic disease but not against colonization in nasopharynx. Control: mass immunization. Upper

Hepatitis B

DNA virus, circular genome. DNA polymerase. Nucleocapsid HBeAg. HBcAg Core antigen. HBsAG Surface antigen. #15 leading cause of death in world. DR Barry Bloomberg discovered HBV, developed test, first HBV vaccine, Nobel Prize in 1976. Variable length, sphere, Dane particle. Empty envelopes in blood. Humans only, Hepadnovirus species specific. Strong tropism for hepatocytes (glandular cells of liver), pathologic effects only in liver. Occasionally found in blood lymphocytes, but does not replicate there. Blood borne (25,000 infectious particles per drop of blood). Transfusions, occupational exposure, needles razors fomites, mother to child prenatal cross placental (6%) or perinatal at birth (94%). Other body fluids. Semen sexual transmission male to female/male. Vaginal secretions female to male. No transmission documented from saliva or breast milk. Entry, transported in blood to liver. Infects hepatocytes (liver cells) but doesn't kill. Cell mediated immunity CMI triggered and cytotoxic T cells destroy infected cell. Loss of functional hepatocyte reduces liver function. Asymptomatic chronic carriers >8% in North of N America, middle of S America, Lot of Africa, Asia. Incubation period 3-6 months. Liver inflammation: jaundice (yellow orange skin and eye sclera), brown urine, hepatomegaly (liver enlargement). General malaise: nausea, fatigue. Recovery of a few weeks to a month. Humoral immunity (neutralizing antibodies to HBsAg Surface Ag), HBcAg, HBeAg (capsid antigens) are protective, prevent further infections. Cell mediated main player, cytotoxic destory infected hepatocytes. CMI weak in chronic carriers probably from exposure in utero, inducing immune tolerance. Diagnosis: Sign, symptom. Test for HBVsAg or anti-HBVsAg (vaccination) indicate current infection. Anti-HBVcAg to core antigen, previous/current exposure but not vaccine. Molecular test PCR for genomic DNA, verification of current infection. Treat: generally bed rest sufficient to enable recovery. Difficult cases, drug treatment used. Interferon to boost immune system. Numerous drugs inhibit HBV replication but don't clear virus. Destruction of infected cells, virus eliminated, recovery. Or failure to eliminate virus, smoldering infection, cirrhosis and carcinoma. Hepatocellular carcinoma is primary liver cancer (white bumps all over). Enlarged abdomen. Age at infection, major determinant of carcinoma. Perinatal, <10% of developing hepatitis, 90% carrier, 25% carcinoma. Adult infection 10% hepatitis, <5% chronic carrier, <10% carcinoma. HBV related disease increased risk: IV drug users, homosexual men, alcoholics (excessive alcohol destroys liver tissue), people infected neonatally. Prevent: 1981 vaccine, composed of empty HBV particles, risk of actual infection. Blumberg: saving lives drew me to medicine. Colleagues: Barry prevented more cancer deaths than anyone, planet improved from Barry few short days in residence. 1st vaccine to prevent cancer. Cancer decline from kids, latency period 10-50 years. 1986: current vaccine subunit recombinant vaccine or HbsAg propagated in yeast cells. HB antigen producing gene into cut plasmid, recombinant, in yeast, ferment, multiply and produce HB antigen, extract and purify. Used to do jet injection (needle free). Potential problem of splash back, retrograde flow, no longer recommends. PRevent: break mother to child cycle of transmission. Screen pregnant women for HBV antibodies, vaccinating. Immediate passive immunization of babies born to infected mothers. Active immunization with vaccine relatively soon after birth. Cases from 27,000 to 4,000. 350 million infected.

SARS-CoV-2 Covid

Enveloped +ssRNA, surface proteins interact with host cell receptors. Frequent cause of respiratory infections in humans and others. Coronavirus transmission: zoonotic, animals to human transmission. Human to human close contact with respiratory droplets by sneezing and coughing. 11 million cases, 530,000 deaths July 6th, Only countries without cases are North Korea, Western Sahara, and Turkmenistan. Spike glycoprotein, envelope small membrane protein, membrane protein, hemagglutinin esterase, Nucleoprotein, Genomic RNA. Viral particles encircled in surface proteins that interact with host cell receptors. Frequent cause of respiratory infections. Respiratory symptoms, fever, cough, shortness of breath, pneumonia. Severe case: respiratory failure, death. Prevent: avoid close contact with sick, avoid touching eyes, nose, mouth. Universal adoption of facemasks, social distancing, etc. Wash hands with soap or water for at least 20 seconds, especially after bathroom and before eating. Pathogenesis: respiratory virus of upper and lower respiratory tract. Mild or no symptoms to severe illness. Most people (80%) recover without needing hospital treatment. Olkder and those with underlying medical problems are at higher risk of developing severe illness. However anyone can catch Covid and become seriously ill. Enters lung, spike protein (receptor binding domain RBD) binds ACE2 (angiotensin converting) receptor by receptor mediated endocytosis. Blocks Endosomal and cytosolic RNS sensors. Interferes with multiple steps during initial innate immune response. Thought to prevent RNA sensing and signaling pathway of type 1 interferon production. Impaired 1 IFN response delays activation of adaptive immune cells and enables diffusion of infection. Lung cells lyse open, release of virions, release of inflammatory molecules and chemoattractants for immune cells. Chemical signals attract and activate alveolar macrophages, major pro inflammatory alarm cytokines (IL6 TNFa, IL1) secreted, inflammation. Macrophage from older adults, impaired 1 IFN and IFN stimulated gene ISG response. Further delays control of infection. Cytokines reach bloodstream, permeabilization. More prostaglandin (PEG2), acts on hypothalamus, leads to rise in body temp, fever. Neutrophils and lymphocytes (++) cytotoxic CD8+ T infiltrate alveoli. Release cytokines, reactive oxygen species (ROS), proteases clear virus. Damage host cells and destroys surface of lung required for oxygen exchange. Accumulation of cells in alveoli causes aggregation (consolidation), cough. Thought to infect immune cells (macrophage, lymphocyte, dendritic), increased cytokine production and maybe Trojan horse. Excess recruitment of immune cells and cytokine production in alveolae (cytokine storm). Covid reach bloodstream, disseminate to other organs. Permeability of vessel and disruption of epithelium result in plasma leakage into alveoli.Plasma leak, alveolar edema, alveolar collapse. Cause shortness of breath, hypoxia. Cocktail of immunogenic mediators into blood. Systemic Inflammatory Response Syndrome SIRS. Important endothelial damage and severe distrubance in blood flow. Blood clotting disorders. Not controlled, rapidly progress to multiple organ dysfunction syndrome MODS, death. More heart troponin, More liver CRP, more kidney CR. Treat: Stage 1 viral response stage, antiviral therapy, convalescent plasma, Stage 2 pulmonary, Stage 3 host hyperinflammatory, immunosuppressive therapy.

!Impetigo

Exogenous strains of Staphy aureus and/or streptococcus pyogenes. Highly communicable in pre and grammar school outbreaks. Early stage: blisters with intense itching. Late stage: pus and crusting with scabs. Often on face. Treat: topical antimicrobial ointment OTC. Prevent: avoid people with impetigo.

MERS Middle East Respiratory Syndrome

Fever, cough, difficulty breathing, last 14 days travel to ME. Wide clinical spectrum from asymptomatic to acute upper respiratory, rapidly progressing pneumonia, respiratory failure, shock and multi organ failure, death. Sero surveys, genetic sequencing: camels likely primary source. Saudi Arabia, Yemen, Oman, Jordan, UAE, Qatar, Kuwait, Lebanon, Iran. Travel cases: UK, france, Tunisia, Italy, Malaysia, Phillipines, Greece, Egypt, US, Netherland, Algeria. Symptom: fever, cought, shortness of breath. Close contact (Caring or living with infected), respiratory?, health care associated infection. Reservoir: camel, bat. No vaccine or chemoprophylaxis. Treatment supportive. Control: standard, contact, airborne precautions for management of hospitalized patients with known or suspected case.

Swine and Avian Flu

Flu A: releasing virus droplets into air from infected person. Virus enters respiratory tract. Virus binds to cells, releases genetic information and starts to replicate. Respiratory tract becomes swollen. Virus moves to bloodstream and symptoms emerge. Member of orthomyxoviridae. Segmented 7 or 8 ssRNA genome with lipid envelope. Antigenic differences in nucleoprotein NP and matrix protein MP classify A, B, C. Further subtyping based on antigenicity of Hemagglutinin HA and neuraminidase NA surface antigens. 17 H and 10 N subtypes in Type A. Widely circulated in humans H1-3 and N1-2. Hemagglutinin: lectin mediates binding of virus to target cells and entry of viral genome into target cell. Neuraminidase: involved in release of progeny virus from infected cells, cleaving sugars that bind mature viral particles. Targets for antiviral drugs. Avian flu: type A, bird disease. NAturally among wild aquatic birds and can infect domestic poultry and other bird and animal species. Disease first identified in Italy more than 100 years ago. 15 subtypes of flu known to infect birds, extensive reservoir of viruses potentially circulating in birds. H5N1 strain of avian flu behind deadly outbreaks. Swine flu: respiratory disease, regular pig outbreaks. Different subtypes and strains. Main viruses in US pigs: H1N1, H3N2, H1N2. Horses have H3N8 and H7N7. Seal H7N7, H3N8, H4N5, H3N3. Bat H17. Antigenic drift: minor changes in N and H. From mutation in RNA segments coding for either HA or NA. No change in serotype, merely alteration in AA sequence, change in antigenicity. An altered RNA segment. Antigenic shift: major changes in H and N from reassortment of gene segments involving 2 different flu. Might cause worldwide epidemics since everyone susceptible. 2 viruses, 1 cell, new virus. Determine extent and severity of epidemics. Pandemic flu: H2N2 Russian Flu 1889, H3N8 Old Hong Kong 1900, H1N1 Spanish Flu 1918, H2N2 Asian Flu 1957, H3N2 Hong Kong Flu 1968, H1N1 Novel Flu 2009. New avian: H7 1900, H5 and H9 since 1990s. 2009 H1N1 spread globally, reintroduced into pigs, host varying strains of swine influenza viruses SIVes around world, since reassorted, new strains, continue to evolve mostly unmonitiored in millions of pigs. Expect H7N9 next influenza outbreak, 83 2015, 28 2016, 192 2017, like 40% death. From 4 separate avian flues. 2 different wildbird contributing H7(N3) from wild duck and (H7/H2/H11)N9 wild bird and 2 different poultry derived H9N2 viruses contributing the other 6 internal genes polymerase, PB2, PB1, PA, NP, and M. Nonstructural NS from other chicken. . 36% chicken, 3% duck, 52% environmental, 9% unspecified.

Bacterial skin infections pyodermas

Folliculitis: staphylococcus aureus. Skin abscess, encapsulated, not reached by antibiotics. Furuncle, carbuncle Scaled Skin syndrome S Aureus Vesicular legions over entire skin surface, fever, most common in infants. Exfoliatins (peeling skin). Scarlet Fever: Streptococcus pyogenes Sore throat, fever, rash caused by toxin, can lead to rheumatic fever and other complications Erysipelas: S pyogenes Skin lesions spread to systemic infection, rare today, but common and fatal before antibiotics. Pyoderma and impetigo: Staphylococci, streptococci. Skin lesions, usually in children, easily spread by hands and fomites. Acne: Propionibacterium acnes Skin lesions caused by excess of male hormones, infection secondary, common in teenagers.

Wound infections

Gas gangrene: Clostridium perfringens, others. Deep wound infection with gas production in anaerobic tissue. Tissue necrosis and death if not treated properly. Gangrene: Anaeorbic, Bacteroides, others Bed sores in severe diabetics. Black, swollen, large deep open wound. Could result in amputations. Cat Scratch fever: Afipia felis and Barlonella (Rochalimaea) henselae Pustules at scratch site, fever, conjunctivitis. Rat Bite fever. Streptobacillus moniliformis Inflammation at bite site, dissemination of lesions. Intermittent fever. Spirillar fever: Spirillum minor. Inflammation at rat bite site heals, later inflammation, fever, rash. Pasteurella multocida: Inflammation at bite site. Eikenella corrodens Inflammation at bite site.

Streptococcal pharyngitis (strep throat), Streptococcus pyogenes (Group A strep)

Gram positive cocci >200 strains, serologic grouping of cell wall carbohydrates used for identification (A, B, C, etc). Reservoir in humans, respiratory route, incubation 3-4 days, duration of illness 3-4 days. Pathogenesis from invasion: M protein of bacterial capsule enables bacteria to escape phagocytosis. Symptom: sudden onset, extremely sore within 30-60 minutes, swallowing painful., headache, fatigue, nausea. Signs: fever, very red throat, lymphadenopathy (swollen lymph nodes) in neck under chin, pus pockets on tonsils and/or back of throat (white lesions), red spots back of throat. Pathogenesis: Cell wall M proteins virulence factors of colonization and resistance to phagocytosis >150 types, differences in virulence and pathogenic mechanism, used for epidemiologic typing. Host produces antibodies to M protein of capsule, enables phagocytosis. Life long protection against same strain, little cross reactivity among >200 strains, can get strep multiple times. Diagnosis: beta hemolysis on blood agar plate. Gram stain of culture. Swab throat in area of tonsils. Point of care quick diagnosis kits, physician office, react with anti strep antibody in kit. Treat: penicillin, usually sensitive, resistance beginning to appear. Upper

AIDS

HIV antibody 1-18 weeks and flu like 2-4 weeks. 1-8 years, shingles, anemia, mild low WBCs, immune thrombocytopenic purpura, seborrheic dermatities, hairy leukaplakia. 9-15 years: anemia, low WBC, low albumin, low cholesterol, low T cell, severe dermatitis, thrush, weight loss, recurring fever, TB, infection, more shingles. Death on average 2 years after AIDs diagnosis, 12-18 months for females, treatment extend life for years. Opportunistic infection, lymphoma, waisting syndrome. Karposi sarcoma, persistent generalized lymphadenopathy (swollen lymph node, neurologic problems. Enveloped retrovirus, RNA, reverse transcribes DNA copy, may integrate into host genome. First: Jay levi UCSF, Robert Gallo NIH, Monatgnier and Barre Sinoussi PAsteur. HIV capsid bullet shaped core with RNA. Envelope, enzymes steps of life cycle. LTR long terminal repeat, transcription of genome, integration, binding site for TFs. gag nucleocapsid core and matrix protein. Pol polymerase reverse transcriptase, protease, integrase, ribonuclease. env viral coat proteins. vif viral infectivity factor, viral replication, overcome inhibitory host enzyme., vpr infect macrophage, replication. tat transcriptional activator elongation of transcript. rev regulator of expression, nuclear export of incomplete spliced. cpu down regulate CD4, more release. nef negative effector less CD4 and MHC1, more release. Human only reservoir. Other species related primate SIV. Cattle BIV. Cat FIV. Selectively infects CD4 helper T cells. DEstroy. Bad: CD4 master regulator of immune, cytokines key to immune, B cell antibodies, activation of immune effector macrophage and dendritic, help activate CD8. Transmitted by sexual contact, kid, injection drug use, occupational, blood transfusion/transplant. 36.7 million in world, 2.1 kids, 1.1 million US. 38,500 new, 6000 deaths. Africa 4.1% have. Global prevalence .8%. Clinical: asymptomatic rare, pre-AIDs influenza like. 2-4 weeks, generalized lymphadenopathy. Fatigue, fever. Severe normal: 2-10 years after initial,more opportunistic, chronic fatigue, weight loss, night sweats, TB. Kaposi sarcoma, HHV8, red bumps. Foot black. Thrush: oral candidiasis. Pharygitis, nausea, vomiting, diarrhea, rash. Pneumocystis pneumonia: cysts of pneumocystis jirovecii (formerly P carnii), fungus, bronchoalveolar lavage. Diagnosis: serological tests for antibodies to HIV as screening method. ELISA. Western blot. Molecular PCR to confirm. Treat: reverse transcriptase inhibitor (AZT azido dideoxythymidine), protease inhibitor interfere with capsid, treatment of secondary infections. Attach to CD4 CCR5, (entry inhibitor, CCR5 antagonist), fusion (fusion inhibitor), uncoat, RT (NRTI, NNRTI stop RT), integration (integrase inhibitor INSTI), transcription, RNA export, translation, assembly, release, maturation (protease inhibitor PI). PRevent: reduce reservoir: theoretically possible by treating active cases, screening pregnant women and treating during pregnancy to prevent transmission to fetus/neonate. Interception of transmission, usual measures to prevent STIs and blood borne transmissions. Increase resistance: no vaccine on horizon, mutates quickly, no vaccine ever against retrovirus, not clear whether to target humoral or cell mediated immunity. Secondary prevention: chemoprophylaxis (truvada) of negative persons who may have been recently exposed or anticipate being exposed. Vaccines: DNA plasmid DNA encoding protein, Adenovirus vector broad tropism, highly immunogenic, pre existing immunity major hurdle. PoxVirus vector, highly attenuated, replication incompetent, very safe, efficient expression vector with large capacity for added DNA, subunit protein recombinant HIV protein. US Federal funding for HIV Aids 31.7 billion, 18.5 billion domestic treatment, 6.3 global, 3.1 cash, 2.8 research, .9 prevention. 35 million infected.

Viral eye disease

HSV1 corneal damage. Herpes Simplex 1. Leading cause of corneal blindness in US and scarring, accounts for 25% of all corneal transplants. Epidemic keratoconjunctivitis. Adenovirus Inflammation of conjunctiva that spreads to cornea. Transmitted in dust particles. Also nosocomial.

SARS Severe Acute Respiratory Syndrome

Hong Kong to international in 2002. 8,422 cases, 916 deaths, 37 countries. Transmission closes contact, respiratory droplet, airborne?. Reservoir: Bats (horseshoe), civet cats, other mild animals sold as food in Guangdong. CFR 10.9%. <1% under 24, 6% 25-44, 15% 45-64, >50% over 65. 349 deaths china, 299 hong kong, 44 canada.

Cold Sores, Herpes labialis. Fever blisters

Human Herpes Virus 1. Human reservoir, transmission in early childhood. Direct contact from kissing, fomites towels and drinking glasses of family members. Initial infection causes inflammation leading to watery blister. Virus kills cells it infects, usually infects nearby nerves. Immune clears skin infection, but virus latent in nerves. Reactivated later when triggered by UV light, fever, stress, moves to nearby skin cells to replicate. Can also infect eye causing super red sclera. Can cause blisters over trigeminal nerve near ear. Painful vesicles, shallow ulcers, systemic symptoms like fever, malaise, myalgias. Herpetic whitlow on fingers, keratitis large eye blood vessels. Simplex encephalitis: rare but potentially fatal brain infection. Necrosis of right temporal lobe. 1 in 500,000. 80% adult population, many subclinical, most common symptomatic: gingivostomatitis in kids, pharyngitis or tonsillitis in adults, infectious keratitis corneal blindness. Has reactivation from nerves like varicella, but herpes goes straight to the skin, while varicella spreads and infects the sensory ganglion before spreading to the skin and causing more pain and inflammation. Diagnosis: signs Treat: most lesions resolve on own. Acyclovir Zovirax (alpha) ointment or tablets for frequent episodes and for eye infections. (Ganciclovir Cytovene for Beta herpes). Guanosine analogs with no sugar. Specifically activated by virus induced kinase, such as thymidine kinase of HSV and UL97 of CMV. Then cellular kinase, then Viral DNA polymerase. Terminate viral DNA chain elongation. Selectively inhibit and inactivate viral DNA polymerase. Prevent: difficult to prevent initial, avoid triggering reactivation. Virus penetrates into skin, replicates. Enters cutaneous neurons and migrates to ganglion, remains in latent state. Subsequently reactivated and travel through sensory neurons to epidermis. Recurrent infection. Often latent in trigeminal nerve, with site of active lesion above lip.

Influenza

Influenza virus, orthomyxovirus, enveloped, spherical, -SS RNA, 6-8 segments. Hemagglutinin (H) envelope glycoprotein attachment and entry to host cell receptor and RBCs, tropism. Neuraminidase (N) envelope protein, enzyme, mobility through respiratory tract mucus, budding of virus particles. Nucleoprotein 3 major types ABC. Nucleocapsid around RNA. M1 matrix protein, M2 ion channel, lipid bilayer, RNA polymerase, NEP. A: Antigenic variation, escape host immunity, periodic epidemics. Hosts also: birds, pigs, other mammals. B: Less extensive antigenic variation, epidemics, human only. C: Rare, different. Antigenic drift: mutations in H and N genes, previous antibodies less effective in neutralizing. Antigenic shift: gene reassortment. 2 different viruses infect same cell, exchange segments. More dramatic changes. Antibody against 1 H not protective against other. Antigenic shift generally precedes pandemic. Like highly pathogenic bird mixes with human. Mixing vessel hypothesis: pig coinfected with human and avian flu strains allows reassortment of RNA segments, could also occur in coinfected human, or by direct avian human transmission. Transmission: inhalation of droplets, contact respiratory secretions. 36-48 hours post infections, communicable first 3-5 days, severity directly proportional to quantity of virus released. Occurrence: Northern temperate (Nov/Dec to April), indoor crowding, poor air circulation. Reservoir: Humans usually infected by human flu, primary reservoir. Birds, pigs sources of new strains through genetic shift. Swine and avian origin flu, mostly wild aquatic birds Flu A. Symptom: high fever, coughing sneezing, breathing difficulties, loss of appetite. Pathogenesis: Invades oropharynx epithelium, spreads to respiratory tract, damage mucus secreting and ciliated epithelial cells (destroyed by replicating virus depleting cellular macromolecules). Loss of mucociliary escalator, bacterial secondary infection, impaired phagocytosis, fluid accumulation. Main site of replication in bronchi. Host: susceptibility factors: age, antigenic similarity, pregnancy (H1N1 2009), immune response humoral and cell mediated. Diagnosis: NP swabs, Viral culture (cell lines), molecular testing (PCR), rapid antigen test less sensitive/specific (esp H1N1 swine origin). Treat: Amantidine stops viral uncoating, Tamiflu Neuraminidase inhibitor stops spread in host from cell to cell (treat within 2 days of symptom start), resistance. Vaccine: Annual, multiple strains, changes every year, Flu vaccines made in chicken eggs. Inactivated still grown in eggs (allergy). Live attenuated, cold adapted, temperature sensitive, Flu Mist, intranasal, nasal replication only. New 2013-14 Flu Season: inactivated grown in continuous cell line (MDCK- Madin-Darby canine kidney). Recombinant Hemagglutinin Baculovirus (insect) grown in a continuous insect cell line (army worm). Flu shot less effective for elderly, 9% H3N2 effectiveness if over 65, instead of over 46%. Poor immunogenicity at age extremes: children 6mo-8yr need 2 doses, >65 years high dose (4x).

Protozoan systemic

Leishmaniasis. Leishmania donovani. Distended abdomen. Malaria, Plasmodium. Mosquitoes. Sickle Cell Anemia prevents. Toxoplasmosis. Toxoplasma gondii. Babesiosis. Babesia.

Brain, Meninges, nerves infections

Listeriosis: Listeria monocytogenes Meningitis in fetuses and immunodeficient. Brain abscesses. Anaerobes. Infection that grows in mass and compresses brain. Hansen's disease. Mycobacterium leprae. Range of symptoms from loss of skin pigment and sensation to lepromas and erosion of skin and bone. Tetanus. Clostridium tetani Toxin mediated disease, muscle stiffness, spasms, paralysis of respiratory muscles, heart damage, usually death Botulism. Clostridium botulinum PReformed toxin from food prevents release of acetylcholine, paralysis and death unless treated promptly. Infants and wound, endospores germinate and produce toxin. Jalapeno peppers, potato salad,, sauteed onions, fermented seafood, baked potatoes, chili sauce. Poliomyelitis. Poliovirus Fever, back pain, muscle spasms, partial or complete flaccid paralysis from destruction of motor neurons. Was around 1/10,000 in 1950. Rabies: Invades nerves and brain. Headache, fever, nausea, partial paralysis, coma, death unless patient has immunity. Encephalitis. Several viruses. Shrinkage and lysis of neurons of CNS. headache, fever, sometimes brain necrosis and convulsions. Eastern Equine EEE, Western Equine WEE, Venezuelan Equine VEE (Togavirus). Flavivirus St Louis SLE. Herpes meningeoencephalitis. Herpesvirus Fever, headache, meningeal irritation, convulsions, altered reflexes. Progressive multifocal leukoencephalopathy. Polyomavirus. JC virus. Infects oligodendrocytes in area of brain lacking myelin. Mental deterioration, limb paralysis, blindness. Transmissible spongiform encephalopathies. PRions. Death of brain cells leaves holes, spongiform brain tissue. Amyloid plaques form, long delay before symptoms. Spasms rapidly worsening to collapse. No cure. Creutzfeldt Jacob disease, Kuru, Scrapie, Mad Cow. African Sleeping Sickness. Trypansoma brucei gambiense, rhodesiense. Fever, weakness, anemia, tremors, shuffling gait, apathy. Parasites invade nervous system, emaciation, convulsions, coma.

Meningitis

Meninges, Meningococcol from Neisseria meningitidis, Haemophilus meningitis, Streptococcus pneumoniae meningitis. Tissue necrosis, brain edema, headache, fever, occasionally seizures.

Common cold

Most common US disease, 2-5/year for adults, 6-12/year in kids. About 50 million US patients/year are prescribed useless antimicrobial agents. 2.9 million on OTC drugs. 276,000 workdays missed because of employee or kid colds. 20 billion/year and 40% of all lost work time. Rhinovirus (non-enveloped), 30-80% of colds. Coronavirus, other virus and bacteria can cause cold like symptom. Human reservoir, respiratory route transmission, incubation period of 2 days, duration of under 1 week. Pathogenesis: multiplies in nose and pharynx causing inflammation, does not invade. Does not go farther down in respiratory tract because multiplies only at 33C (91.4 F), cooler temp of nose. Subjective symptoms: fatigue, headache, tingling nose, occasionally sore throat. Observables: nasal congestion, runny nose. Diagnosis: usually self diagnosed, no lab test available. Defense IgA but short lived. Palliative treatment of symptoms but doesn't cure. Antihistamines and anti inflammatory drugs reduce inflammation. Decongestants shrink blood vessels in nose and reduce swelling of nasal passages. No effective antimicrobial therapy. Preventative: avoid people, avoid contaminated fomites, frequent washing of hands and potential fomites. Difficult to control: endemic, 100 strains, immune responses don't cross react, IgA wanes after 6 months (no blood, so no IgM or IgG), survive at least 3 days outside of body (fomites). Vaccines too difficult to develop and not worth the effort because benign disease. Upper

!Rabies

Most deadly infectious disease. 8 people developing disease survived, 5 probably previously vaccinated, 3 treated experimentally. Does not follow iceberg. Rabies virus helical, enveloped, rod or bullet shaped, -ss RNA rhabdovirus. Reservoir: dog, cat, fox, bat, mongoose, raccoon, skunk. Transmission: shed in saliva, transmitted when animal bites, also by exposure to bat feces. Pathogenesis: virus multiplies in tissue around bite, travels up peripheral nerves to brain over 1-3 months, replicates slowly, destroys cells in CNS, acute encephalitis in 20-60 days, moves to salivary glands. Ancient, feared, Aristotle 4th century BC. Italian Adelchi Negri inclusion bodies, Negri bodies (dark pink dots), cluster of virions in neurons. Clinical: pain at site of wound except bat bites maybe painless, neck pain 2 months later, loss of control of movement, throat muscle paralysis, difficult swallowing, drooling, hydrophobia fear of water, behavioral changes, extreme agitation, coma, death 3 months after exposure. Diagnosis: usually after death from autopsy of human or animal Negri bodies in brain, PCR of brain or other material. Samples from wound, fluorescent antibody test (patient antigen, laboratory antibody), PCR. Treatment: Antiviral: no established antiviral treatment, 3 humans in 2004 survived with ribavirin and amantadine antiviral agents and medically induced coma. Immunologic treatment: passive immunization injected around wound, active immunization with inactivated vaccine, 3 injections in the arm each 1 week apart, type of secondary prevention, virtually 100% effective, original Pasteur vaccine 14+ daily injections in abdomen of live attenuated. Prevention: animal control, vaccination of dogs in most developed countries, cat recommended, quarantine of imported in rabies free areas, wildlife surveillance and reducing stray unvaccinated populations. Vaccinate people at risk of exposure: occupational outdoor work with wildlife exposure, lab personnel, travelers to high risk areas. Public education. High risk in developing areas. Incidence has been 2 cases per year since 1990. Rabies reservoir in US: raccoon east coast. Skunk in central and CA. Fox in AZ and Alaska. Mongoose in PRico. Mostly raccoons, then skunks and bats, used to be mostly skunks. Common in Asia, Africa, South America.

Wounds infected

Most wounds small and superficial, exposed to O2 in air and aren't anaerobic. Wounds likely to become seriously infected have inadequate blood supply or lack O2 for another reason. Injuries deep into tissue, surgical wounds: blood vessels cut, no O2. Injury with contaminated object can deliver microbe deep into tissue. Poor or no circulation: extremities of severe diabetics, excess glucose narrows vessels. Undergoing chemotherapy or on medications. Areas not accessible to blood circulation and benefit of immune response (cysts). Microbes: Microaerophilic bacteria, reduced O2. Anaerobic only in absence of O2. Facultative: with or without O2. Bacteria produce enzymes that kill tissues. Dead cell areas become anaerobic, no blood supply. Bacteria multiply in dead tissue. Infection spreads rapidly by direct extension.

Respiratory tract

Nasal cavity nasal sinuses, pharynx (throat), larynx, Trachea, Bronchi (upper respiratory), Lung (lower respiratory). Epiglottis keeps food out of lungs. Moves oxygen to blood, removes CO2. Major source of microbes. Nasal cavity hair and mucus remove some. Nasal sinus: hollow cavities, mucus membranes (sinusitis). Pharynx (throat) common link respiratory and digestive system (pharyngitis), auditory Eustachian tubes connects to middle ear. Upper defenses: normal microflora, nose hairs filter large particles, epithelial barrier, mucus membranes lining nasal, pharynx trap microbe, prevent passing beyond pharynx, contains lysozyme (hydrolysis of peptidoglycan), respiratory mucus secreted by goblet cells. Coughing, sneezing increase exposure to mucus, expel irritants. Nasal cavity and bronchi ciliated epithelia, trap and move microbes to pharynx (mucocilliary escalator ciliated mucus epithelium), microbes, bronchi debris moved to pharynx and expelled. Phagocytic cells (neutrophil, macrophage), local antibody production, mostly IgA (Secretory antibody) and IgG.

Chagas. Trypanosoma cruzi.

Nerve disease. Subcutaneous inflammation, damage to lymphatic tissue, muscle, nerve ganglia, muscle pain, paralysis of intestinal, heart, skeletal muscle. Reduviid bug bites sleeping human. Localized reaction to injected parasites (chagoma), swelling. Amastigotes form within monocytes in subcutaneous cells. Trypomastigotes released into blood. Change to amastigote forms and reproduce. Reticulotropic and myotropic strain. Intracellular amastigotes change into trypomastigotes and are released into blood. Globular shaped megaheart. Megacolon. Ingested by reduviid bug when bug boted. Alternate host of rat or armadillo. Trypomastigote multiply in bug midgut. Endemis in Central and southern America. Spreading to US, Canada, Europe, other countries, many illegal immigrants.

2009 H1N1 Influenza

New swine flu virus. (pieces of RNA) Similar to avian, human, swine viruses. 1990: Human H3N2, Avian, and Classic swine H1N1 combined into North American Swine H3N2 and H1N2, combined with classic swine H1N1, then Eurasian swine to make.

Outer ear Otitis externa disease

Outer ear infections, Staphylococcus aureus gram positive cocci in clusters. Pseudomonas aeruginosa: gram negative bacilli Fungi: candida albicans (yeast), aspergillus fumigatus

Staphylococcus aureus wound infection

Part of skin microbiome, causes minor skin infections. Facultative so both aerobic and anaerobic. Highly antibiotic resistant strains, MRSA (methicillin beta lactam resistant staph), often cause fatal infection. Serious: cellulitis deep tissue infection from wound. Skin black, yellow, inflamed, pustule, Ganglion cyst: from between bones, needle used to remove fluid.

Scarlet Fever

Particular strains of Streptococcus pyogenes infected with bacteriophage that codes for erythrogenic toxin, exotoxin (produced by bacteria in environments). Signs: special manifestations in addition to usual signs. Rash spares palms and soles, lasts about 1 wk then fades. Feels rough to touch. Rash on hard palate (super red along with dots). Upper

Candidiasis. Candida albicans.

Patchy inflammation of mucus membranes in mouth (thrush) or vagina (vaginitis). Disseminates nosocomial infections occur in immunodeficient patients. Diaper rash, skin under breasts, mouth thrush. Human reservoir, endogenous microbe soon after birth. Pathogenesis: most areas of skin, inhibited by endogenous bacteria and cell-mediated immunity, common in immunosuppressed people or undergoing heavy antibiotic treatment. Diagnosis: direct smear. Treatment: topical antifungal ointment. Wiping of tongue and antifungal mouthrinse. Prevention: avoid letting skin areas get moist, apply talcum or antifungal powder. Minimize systemic antibiotic treatment. Correction of underlying immunosuppressive disease.

Lice

Pediculous. Pediculus humanus body/head louse, no winged insect. Inflammation at louse bite sites and itching. Phthirus pubis (pubic/crab louse, insect no wings) found in pubic areas. Mostly transmitted by fomites. Survive 7-10 days without blood meal. Eggs on a thread like structure. Hair, clothing, mattress, bedding, upholstery. Take over 2 days to hatch. Inflict tiny wounds by biting and sucking blood, may cause slight itching. Historical association unclean, currently all socioeconomic classes. Diagnosis from finding lice embedded in skin or by nits (debris often confused, but white not translucent). Treat: A200 kills. Topical petroleum derivatives, OTC, many lice strains now pesticide resistant. Comb with closely spaced teeth to remove nits. Prevent: sterilization of combs and brushes used in salons. Sterilization of used clothing and upholstered furniture before selling. Fitting room regulations for underwear but not for hats. School nurses in grammar school required to periodically screen for lice on scalp.

Defenses of circulatory system blood/lymph

Phagocytic cells: neutrophils, monocytes, (macrophages). Filtering action of lymph nodes and spleen. Trap infectious agents and facilitate phagocytosis. Stimulate lymphocytes to produce antibodies. IgG and IgM if host exposed naturally or through vaccination. No microbiome, blood normally sterile.

Respiratory disease facts

Pneumonia 3rd leading cause of death worldwide. Most deaths in children living in poverty in developing countries. #1 killer of children under 5. #1 in developing countries, then diarrheal.

Viral skin infection

Rubella virus Mild disease with maculopapular exanthema (discolored, pimply rash), infection in early pregnancy can lead to congenital rubella. Vaccine has greatly reduced incidence. Measles. Rubeola virus Severe disease with fever, conjunctivitis, cough, rash. Encephalitis complication. Mainly in children. Vaccine. Roseola Human herpesvirus 6 Sudden fever, rose colored rash, virus shed in saliva. Smallpox virus Eradicated by immunization as human disease. Other poxviruses Clear or bluish vesicles on skin surface, human infections rare. Cowpox, monkeypox, molluscum contagiosum.

Helminth blood diseases

Schistosomiasis, Filariasis Elephantitis

Bacterial septicemias

Septicemia: Staphylococcus aureus, streptococcus pneumoniae, septic shock, lymphangitis. Diagonal red arm streaks. Bacterial endocarditis: Strep and Staphy, Myocarditis, Pericarditis. Clots accumulate on surface of disaeased valve, bactermia, bacteria attach to clots and grow, leading to vegetation. Circulating immune complexes. Continuous bacteremia and metastatic focus of infection. Bits of vegetation break off into circulation, clots that can clog blood vessels.

transmission bioaerosols

Small particle (droplet nuclei <10um): distant spread >1.8 m, close contact with infectious source not required and may not be evident, rapid explosive outbreak. Large particle droplet 1-100 um: close contact >.9 m necessary, spread slow, intermittent, variable, without clustering of cases, may go unrecognized. Fomites self inoculation: direct contact with infectious secretions contaminating environmental surfaces, infectious secretions transferred from hands to respiratory, most spread with close and prolonged contact and those with poor hygiene (family and day care).

Impaired host defense

Smokers lose cilia and mucus production, more toxic substances in lungs. Decreased ciliary function and number. Cause increase in mucus production. Increased risk for all respiratory diseases. Inhaled pollutant or dust: cause damage that exposes more epithelial cells, greater bacterial colonization Impaired cough or gag reflexes: advanced age, drugs narcotics and alcohol, intubation Advanced age.

Fungal skin diseases

Sporotrichosis: sporothrix schenckii or Blastomycosis: Blastomyces dermatitidis. Granulomatous, pus filled lesions that develop in lungs and wounds, sometimes disseminates to lungs and other organs. Aspergillosis: Aspergillus species Wound infection in immunodeficient patients, also infects burns, cornea, and external ear Zygomycosis: Mucor and Rhizopus species Mainly with untreated diabetes, starts in blood vessels and can rapidly disseminate.

Anatomy of skin stuff

Tear Flow: Lacrimal gland, excretory lacrimal duct, superior or inferior lacrimal canal, lacrimal sac, nasolacrimal duct, nasal cavity. Skin: corneum, granulosum, spinosum, basale, dermis with fibroblasts, elastic fibers, blood vessels. Defenses: Keratin in outer layer of epidermis, main protein in hair and nails, physical barrier. Sebaceous gland secrete sebum (skin oil) on surface, inhibits growth of some bacteria. Microbiome: endogenous microbes, mostly bacteria, few fungi, inhibit pathogen. Lysozyme present in tears inhibit Gram positive bacilli. Inhibit growth of pathogenic bacteria. Inhibit growth of yeast. Microflora. salt tolerance, skin cell shedding.

Arthropod/Insect Bites and Infections. Ectoparasites.

Tick paralysis. Various ticks. Toxins introduced with tick bite cause fever and ascending motor paralysis. Chigger dermatitis. Trombicula mites. Larvae burrow into skin and cause itching and inflammation. Can cause violent allergic reactions. Flea bites. Tunga penetrans. Itching and inflammation from adult females in skin. Blackfly fever. Blackfly Bites cause severe inflammatory reaction in sensitive individuals. Myiasis. Fly larvae Maggots infect wounds in animals. Congo floor maggot sucks human blood. Screwworms injure cattle. Mosquito, other bites. Mosquito, some flies, bedbugs. Painful, itchy bites, several insects serve as disease vectors.

Toxoplasmosis

Toxoplasma gondii. Protozoan parasite. Phylum apicomplexan. Reservoir: cats and other felines. Transmission: Ingestion of material contaminated with cat feces. Cats definitive hosts, sexual cycle occurs only in intestine of Felines. Birds, rodents (cat eats), ungulates, human intermediate host, forms cyst in tissues, transmission from eating undercooked beef. Can also be transmitted vertically to baby or by blood transfusion. Ubiquitous invades all cell types, worldwide zoonosis. Seropositivity increases with age. 90% seroprevalence by 4th decade of life (France, El Salvador, Tahiti), up to 70% of healthy adults in US infected with Toxoplasma. Worldwide 30%. Opportunistic infection associated with AIDS, 15-40% HIV+ infected in US, up to 96% in parts of Europe and Africa. Up to 47% Toxoplasma infected HIV+ will develop toxoplasmic encephalitis (increases as CD4+ cell count falls). Infection mostly asymptomatic from immune system control, severe and possibly fatal in immunocompromised from encephalitis, neurologic disease. Small kids: fever, rash, pneumonia, encephalitis. Can cross placenta in 40% of fetuses of non-immune mothers. Cause: miscarriage, 12% of babies die shortly after birth, <20% are normal after age 4, damage to CNS, hydrocephaly, blindness (retinitis), mental impairment, motor disturbances. Diagnosis: direct smear of material from spinal fluid or blood, ELISA serum antibody, PCR. Goes in monocytes. Treat: sulfonamide, pyrimethamine, sulfadiazine (inhibit folic acid synthesis). Protozoans need folic acid in bigger amounts than host. Prevent: avoid raw or undercooked meat, prophylactic antimicrobials for non-immune pregnant woman who has been exposed. Don't have a cat, or only an indoor cat. Indoor outdoor cat: hygienic food prep cats off tables, wash hand between cat and food. Cautious about kitty litter: pregnant don't touch. Importance: antibodies seroprevalence in US 11%, much greater elsewhere, especially Latin America (50-80% of population). 75-80 million pet cats, 30-40 feral in US. 1/3 number of humans. Infected mice lose instinctive fear of smell of cats and parasite's effects maybe permanent. Behavioral manipulation Animals: greater predation of intermediate host by definitive host. Rat/mice: increased nonspecific movements, more active. Reduced neophobic behavior: less fear of new scents and sounds. Reduced aversion (fatal attraction) to cat urine. Reduced learning behavior. Infected whale: less able to flee from attacks, draw attention of sharks from abnormal movement. More sexual transmission: male infected rats more attractive to females. Human chronic infection: schizophrenia, suicide attempts associated with seroposivity, epilepsy, congenital toxoplasmosis may reduce brain function, loss of psychomotor performance (increased traffic accidents), more anxious. Men more jealous, emotionally unstable, suspicious, short tempered, low self esteem, disregard social rules. Increased dopamine, decreased tryptophan. Increase predation. Mechnism: tropism to specific regions (amygdala, ventral hippocampus, associated with conditioned or learned fear), disruption of dopamine signaling. Dopamine: motivation and goal directed behavior, atypical motivation to explore predator odor. Hormonal upheavals and concomitant epigenetic changes, tweaking of communication lines between brain and gonodal hormones, upregulation of testosterone synthesis and increases male sexual pheromone. Shifts behavior towards sexual behavior and away from defensive behavior.

Bacterial eye

Trachoma Chlamydia trachomatis Infection and destruction of cornea and conjunctiva, cause of preventable blindness. Keratitis Bacteria, virus, fungi. Ulceration of cornea, mainly in immunodeficient and debilitated patients. Ophthalmia neonatorum. Neisseria gonorrheae. Infection acquired during passage through birth canal, corneal lesions and can lead to blindness. Silver nitrate or antibiotics have nearly eradicated it in developed countries. Bacterial conjunctivitis Haemophilus influenzae biogroup aegyptius, staph aureus, Strept pneumoniae, Neisseria gonnorrhoeae, Pseudomonas Highly contagious inflammation of conjunctiva in young children. Most eye infections are caused by bacteria. Also adenovirus. Most occur on conjunctiva (inner eyelid). Give babies silver nitrate eyedrops to prevent infection, twinkle in their eye. Now antibiotic ointment.

Lung Fluke, Paragonimus westermani

Transmission: consumption of raw or undercooked seafood, pickling doesn't kill encysted larvae. SE Asia and Japan. Other species common in Asia, Africa, S+C America. Reservoir: humans and other mammals definitive hosts and act as reservoirs. Snails, crabs intermediate hosts. Water: Unemryonated eggs to Embryonated eggs, miracidia hatch and penetrate snails, sporocyst, rediae, cercariae, invade crustacean and encyst into metacercariae, humans ingest inadequately cooked or pickled crustaceans, containing metacercariae, exocyst in duodenum, adults in cystic cavities in lungs lay eggs which are excreted in sputum or eggs swallowed and passed with stool. Disease: pulmonary manifestations cough, expectoration of discolored sputum, hemoptysis. Infection can resemble TB. Heavy infestations: lesions in lung, liver, and brain. Diagnosis: eggs in sputum of feces. Treat: praziquantel Prevent and control: no vaccine, education thorough cooking of crustaceans, dispose of sputum and feces in sanitary manner, control snails where feasible.

Dermatomycoses, dermatophytes, "ringworm"

Tricophyton, microsporum, epidermophyton. Dry, scaly lesions on various parts of skin, difficult to treat. Often ring shaped lesion. Reservoir: human, animal or soil depending on species. Athlete's foot Toe Jam. Can infect toenail or scalp. Groin ringworm: jock itch or crotch rot. Transmission by direct contact of skin with reservoir or fomites (towel, bedding, clothing). Cells of immune system can't reach granulosum and corneum, so grow and destroy. Keratin nutrient for fungi. Blood products diffuse into spinosum, basale, collagen matrix, so dermatophyte growth inhibited by cell mediated immunity and serum substances operating in this area. Diagnosis: Wood's light UV useful but does not reveal all species. Fluorescing dermatophyte. Microscopic diagnosis from skin scraping. Special agar fro growing dermatophytes may help diagnose. Test medium. Grow, pH alkaline, turn from yellow to red. Treat: topical ointment OTVE, clotrimazole. Tincture of iodine applied topically. Severe: oral Griseofulvin inhibits mitotic spindle of fungi. Prevent: keep dry, loose cotton underclothing, antifungal body powder or ointment between toes, avoid inflamed bald spots.

Endemic diseases

Tuberculosis, Respiratory, Diarrheal, Malaria, Helminth worm. Key factor: Poverty, poor sanitation/hygiene, malnutrition, overcrowding

Bacterial systemic

Tularemia, Francisella tularensis. Ulceroglandular. Typhoidal. Common around oklahoma, arkansas, and missouri mostly. Brucellosis. Brucella. Undulant fever. Squiggly Relapsing fever. Borrelia. Borrelia burgdorferi lyme disease. More common, New England, Great Lake.

Rickettsial

Typhus fever: Rickettsia prowazekii. Epidemic/endemic/scrub typhus. Brill-Zinsser disease. Rocky Mountain Spotted Fever: Rickettsia rickettsia. Rickettsialpox: Rickettsia akari.

Rubella, RubeolaGerman Measles

Vaccine made incidence go from .29% to basically 0. Was more common than measles. Has Koplik's spots in mouth. Encephalitis. SSPE.

Warts. Human papillomavirus.

Viral skin infection. Dermal warts are self limiting. Malignant warts occur in immunological deficiencies. 99% of cervical cancer. Papillomas. Transmission: dermal or genital. Particular strains cause common skin warts. Human reservoir. Transmission: direct skin skin contact or via fomites (towels, manicure instruments). Autologous transmission, spread to different parts of own body. HPV multiplies in lower layers of epidermis (basale, spinosum?) without killing cells. Alters growth properties, causing excess of cells to accumulate. Can get some big bumps. Plantar warts on soles of feet where shoe applies pressure. Juvenile flat warts on face, not removed because usually disappear spontaneously at around 2 years. Diagnosis: Appearance no protective immune response. Treat: destruction of wart tissue. Freezing liquid nitrogen or dimethyl ether. Burn with cauterizing needle. Laser beam. Acid treatment. Prevent: Avoid using towels or manicure instruments of others. Wear properly fitting shoes.

Influenza nomenclature

Virus type of nuclear material/Geographic origin/Strain number/Year of Isolation (Hemagglutinin Neuraminidase = Virus Subtype) A/Fujian/411/2002 (H3N2)

Scabies. Sarcoptes scabeii. Arachnid.

Widespread lesions with intense itching. Other mites cause house dust allergy when feces inhaled by allergic individuals. Skin/skin contact. Burrow into epidermis and make tunnels where mating and reproduction occurs. Excretions cause severe allergic reactions. Diangosis based on microscopic appearance of material removed with needle. Pudgy spiky things. Treat: ointment, liquid containing sulfur. PRevent: avoid contact with infected or fomites.

Emerging

Within humans or from zoonotic. New disease for known infectious agents, or new discovered infectious agent for known disease. Health departments, chlorine, no plague, penicillin, Salk Vaccine, Vaccination Assistance Act. 1900, mostly pneumonia, TB, gastrointestinal, heart, cerebrovascular, nephropathies, accidents, cancer, senility, diphtheria, 1.1% died a year. Now Heart disease, cancer, noninfectious airway disease, accident, cerbrovascular, alzheimer, diabetes, pneumonia and flu, nephropathies, suicide, .6% die a year. Top 10: heart disease, lung cancer, chronic lower respiratory, accident, stroke, breast cancer, alzheimer, diabetes, prostate cancer, influenza pneumonia. Affect eradication: highly adaptable microbes. travel, commerce, and immigration introduce new or recurrent strains of pathogen. Available medical expertise not always applied. Previous unknown or rare diseases become significant as a result of changes in human activities or social conditions.

Inner ear, Otitis media disease

Young children get more: eustachian tubes are smaller and more level in kids, difficult for fluid to drain out of ear even under normal conditions. Tubes blocked or swollen with mucus from cold or other respiratory, fluid might not be able to drain.

!Pyoderma, staphylococcus aureus, pus

Zit, pimple, boil, acne. Whitehead. Pus containing lesion of skin and eye Pus is collection of bacteria and leukocytes. Gram positive cocci in clusters. Human reservoir, part of endogenous skin and nose microbiome. Transmission: direct contact of skin with reservoir or fomites. Treat: topical antimicrobial ointment (OTC), neosporin. Antimicrobial eye drops for eye infections. Prevention: refrain from rubbing eyes with hands. Good skin hygiene. Avoid shaving too close.

Anthrax

Zoonotic. Herbivore: sheep, goat, cattle, reindeer (Siberia 2016), acquire from contaminated soil, carnivore from consuming meat. Not spread animal to animal. 20-100,000 cases/year (Africa, Asia, Caribbean), many more in animals. Prior to 2001 letter attack (22 cases, 11 inhaled, 11 cutaneous, 7 states, 1 epizootic cutaneous)), only 5 cases since 1980, decreased mainly from 1950 to 1963. Naturally acquired inhalation cases. Bacillus anthracis (1877 Robert Koch) Large, gram positive, bacilli, facultative anaerobe, endospore forming: only form in aerobic conditions, not found in tissues or blood, viable for 60-100 years. Human transmission: contact with endospores during occupational exposure, wool, hides, meat, bones. Wool sorters disease respiratory anthrax. 90% cutaneous skin lesions, center black and necrotic (CFR 10-20% untreated, 1%). 5% respiratory anthrax (uniformly fatal), most deadly, most bioterrorism concern, similar to flu symptom, inhaled into lung, spore germinate in alveoli, phagocytized by macrophage, replicate, swollen lymph nodes. 5% intestinal anthrax (CFR, 25-50%), mimic food poisoning, lesions or ulcerations in digestive tract, septicemia and death, outbreak unpasteurized goat's milk cheese. bacteremia: meningitis in 5%. Virulence factor: Plasmid pX02 capsule glutamic acid. Plasmid pX01 3 exotoxins, edema factor, lethal factor, protective antigen, swelling, prevent phagocytosis by macrophage, release of inflammatory cytotoxins. Swelling, blood clots within capillaries and lymph nodes, airway obstruction. Diagnosis: blood culture, gram stain, culture external lesion, immunoserological, PCR. Treat: Ciprofloxacin (fluoroquinolone), other more common antibiotics penicillin, doxycycline, erythromycin. Prevent: vaccine exists, 6 doses over 18 months, reduce exposure to endospores, dispose of infected animals properly, vaccinate animals. Reservoir: animals, contaminated soil. Bacterial systemic.

!Herpesvirus

a. HSV1, HSV2 (Herpes simplex). 3 Varicella Zoster Virus VZV. Relatively rapid, cytocidal growth cycle. Latent infections primarily in sensory ganglia. B. 5 cytomegalovirus CMV. HHV6 HHV7 Human herpes. long reproductive cycle, grow slowly in culture. Establish latency in monocytes (CMV) or T cells (HHV). y. 4 Ebstein Barr Virus EBV. 8 Kaposi sarcoma KSHV/HHV8. Latency in B cells. Can transform lymphoid cells. Oncogenic herpesvirus. Ancient class, unparalleled ability to infect nearly all cell types Large dsDNA, unparalleled number of mechanisms to evade immune. Nearly 90% of population has at least 1 herpesvirus. HHV1: direct contact, fomite, reactivated, no vaccine, nerves privileged. HHV2: 10-30% of adults, many asymptomatic. Direct contact, birth, no vaccine, neonatal rare but dangerous. Genital, anal lesions. Latency sensory nerves, reactivation. Epstein Barr: infectious mononucleosis. B cells and epithelial. 1958 first described in childhood tumor by Dr Burkitt. 1964 identified by Epstein and Barr by EM. 90-95% of adults show evidence of infection. Latent phase antigen: EBNA1 essential for EBV episome maintenance, oriP. LMP1 and LMP2 repress reactivation. Most potent transforming agent, widespread, usually asymptomatic persistent infection. Sometimes associated with pathogenesis of certain lymphoid and epithelial cancers including Burkitt lymphoma: Africa, cheek swelling in kid, B cell centrocyte, malaria, AIDs, chromosomal translocation causing deregulation of myc oncogene, nasopharyngeal carcinoma: East Asia, Bit of Africa, Alaska and Greenland, less than 1/10,000, looks like stroke, epithelial, all EBV. First, low grade then high grade pre-invasion lesion. LOH, inactivation of RASSF1A and CDKN2A, EBV latent, telomerase deregulation, BCL2 overexpression, other genetic changes. Hodgkin disease: 40-50% of patients EBV seropositive, Reed Sternberg cell. Immunblastic lymphoma in B cell lymphoblast, all EBV positive, IAtrogenic immunosuppression in posttransplant, HIV induced suppression. Sinonasal T cell lymphoma, T cell, over 95% EBV. Human Tumor virus. Significant problem in AIDS patients: oral hairy leukoplakia on tongue. EBV infects B blast, LMP1 and 2a expressed, nondividing memory cells, cytotoxic response and die (most), malaria related compromised immune: multiply, rare Ig c myc trasnlocation, suppressed expression of most viral signs, Ig c myc+ EBNA1+ proliferating, surviving, Burkitt lymphoma. Lymphoid and epithelial malignancies. EBV encoded latent genes induce B cell transformation by altering transcription and constitutively activating key cell signaling pathways. Exploits normal B cell differentiation to persist within memory B cell pool of immunocompetent host. CMV: monocytes, asymptomatic, severe if immunocompromised. Important congenital. No vaccine. Ubiquitous, 80% of adults, 79% US, 100% India, super common Asia and Africa. Latent in myeloid progenitor cells, reactivates during pregnancy and immunosuppressed, cytomegalic inclusion disease, CMV pneumonia, retinitis, hepatitis. Transmit body fluids during breast feeding, blood transfusion, organ transplant. Immunecompetent: asymptomatic. Cancer, transplant, AIDs, other deficiency severe disease of lung, liver, colon, eye, brain. LEading cause of birth defects and mental retardation in newborns, 10% of infected fetus exhibit damage of CNS, hearing loss, impaired vision. More than 95% of organ transplant mortality. One of most common opportunistic infections in AIDS, common immediate cause of death 25%, 70-90% active infection, 30-40% CMV retinitis. Potential agent for atherosclerosis, restenosis and other cardiovascular. Injurym, reactivatem, inactivated p53 and other mechanism, lesion. 6 and 7. Exanthema subitum in infants, CD4+ T, No vaccine. 6: Roseola or exanthema subitum ES or 6th disease, sudden fever for few days, rash on trunk and face in infants. Isolated 1986 AIDS. HHV6A neurovirulent. HHV 6B roseola. Up to 90% of kids infected by age 2. Transmitted from mom or other kids. Variety of human cells involved, latent in T cell. Reactivation in immunosuppressed and compromised. &: isolated 1990, similar/dostinct from 7, Infect and latent in T cell, ubiquitous 95% of adults have antibody, causes diseases like HHV6 but less frequently. 8 Karposi Sarcoma with HIV/AIDS, B cells. Red, blue, or purple flat or raised lesions. No vaccine. Moritz Kaposi 1870s. Cancer in connective tissue, blood vessel tumor. More common in AIDS patients, 91,000 people with AIDS 1989, 15% KS, over 20,000x more common in AIDS, 300x more common in immunosuppressed. Sexually transmitted factor other than HIV plays role, 10x more common in homo or bisexual men. 1994 PCR Chen and Moore 2 DNA fragments homologous to EBV. Found in virtually all AIDS KS tumors. Unique among herpesviruses. Not ubiquitous, infects B cells, encodes many cellular homologues. vIL6 growth factor, vBCL2 anti apoptosis, vIRF inhibition of IFN signaling, vCYC cell cycle control. Possible association with cancer, cardiovascular disease, heuronal disorder. Icosahedral, nuceocapsid, large linear dsDNA, envelope, tegument, glycoprotein. Viral DNA syn thesis and capside assembly in nucleus. Unique tegument layer, transcription factors. PRoductive and latent infection. Attach and penetrate, uncoat and release vDNA, transcription, protein synthesis, replication, assembly nuclear capsid. Assembly, packaging, release of virions. Alzheimer viruses: Hep C, HHV 1 2 3 chciken 4 EBV 5 CMV 6.

Acne, Proprionibacterium acnes

gram positive bacillus, facultative bacterium, grows well in absence of oxygen, lives in lower sebaceous (oil) glands. Human reservoir, part of skin microbiome. Transmission shortly after birth from other humans. Blachhead comedone: bacteria, sebum, dead epidermal and melanocytes (dark color), inflamed areas around blackhead from acids released when sebum is metabolized by P acnes. Host factor: genetic inherited. Hormones: sebum production stimulated by androgens (male hormones), males higher incidence of severe acne than females. Females produce androgens on monthly basis in middle of menstrual cycle. Diagnosis: signs. Mild acne: face a bit red and bumpy. Severe acne: larger, blacker bumps over more of body. Prevent: hygiene wash hands with hot not cold water. Treat: Peeling agents: cause exfoliation of excess epidermal cells. Low dose topical chemicals benzoyl peroxide. Oral antibiotics reduces number of P acnes organisms eg minocycline. Female hormones for severe acne. Acutane for severe acne: inhibits full differentiation of skin cells into oil producing cells.

Zoonosis, zoonotic infection

human infectious disease originating from animal reservoir and not requiring human as part of its life cycle. Can circulate among animals without human. Human accidental host. Helm inth and others that have animal involved as intermediate host are not zoonotic because human needed for life cycle. Many infections with human reservoir started out as zoonotic, human host parasite relationship evolved, became uniquely human (not zoonotic), example smallpox from camelpox, measles from cattle rinderpest, TB from M bovis, HIV from SIV (simian). Current zoonotic from more recent exposure of humans to microorganism, slower evolution of host parasite relationship.

Diseases of respiratory

itis inflammation Pharyngitis: sore throat, viral and bacterial Laryngitis Epiglottitis: infection of epiglottis, can close airway, serious Sinusitis Bronchitis Tonsilitis Croup: laryngotracheobronchitis usually viral, involves larynx and epiglottis. Difficulty breathing, spasm of larynx, barking seal cough. Ear infection: part of upper respiratory, eustachian connects to pharynx of respiratory.

Ebola, Zaire

linear, nonsegmented, single strand RNA genomes of negative polarity. Filamentous particles that may appear in shape of U or 6, shepherds crook, coiled, toroid, branched. Median particle length 974 to 1086 nm, 80 nm in width. From fruit bats (pteropodidae natural host), but don't know how transmits between bats. Sporadic epizootics, high mortality, primates and duikers. Acute disease in humans, don't know how gets to humans other than from blood, secretions, organs or other body fluids of wild animals (chimps, gorilla,s fruit bats, antelope, monkeys, porcupines found ill or dead in rainforest). Also, Sudan, Tai Forest, and Bundibugyo viruses. BEtween humans: direct contact with blood or bodily fluids of infected or exposure to objects (like needles) that are contaminated with infected secretions. Often spread through families and friends because close contact while caring for ill. Spread quickly in healthcare settings, not appropriate PPE, proper cleaning and disposal of instruments, need adequate sterilization of transmission continues and amplifies. Symptoms: headache, red eyes, hiccup, sore throat, difficulty swallowing or breathing, chest pain, stomach pain and vomiting (sometimes bloody), skin rash or bleeding, diarrhea (sometimes bloody), joint ache, muscular aches or weakness, fever, lack of appetite, internal bleeding. Treat: supportive, balancing fluids and electrolytes, maintain oxygen status and blood pressure, treat for complications. First 1976. Few hundred every few years. 2014, multiple countries (Sierra Leone, Liberia, Mali, Nigeria, Senegal, Guinea), over 25,000 infected and over 10,000 died, but bit lower mortality than normal. Outbreak in DRCongo in 2018. rVSV-ZEBOV vectored vaccine works since 2017.Tried using monoclonal antibodies to treat advanced disease in primates and humans.

Plague. Yersinia pestis.

major population depleting epidemics in last 2000 years. Killed 1/3 of world in pandemic of 1300s, most recently in India 1995. Yersinia pestis, gram negative coccobacillus. Prairie dog, rat, chipmunk, squirrel. Last 25 years, mostly around 30 degrees latitude. Requires (squirrel) flea biological vector. Bacteria multiply in flea gut and block it, causing flea to regurgitate infected material when feeds on new host, flea is in starving state so it bites frantically. Multiples in lymph fluid and lodges in lymph node nearest site of flea bite. Bubo: enlarged lymph node black from hemorrhage and fever occur within 2-6 days. Disease not communicable among humans yet. Pneumonic: only 5% of cases, bacteria enter blood and disseminate to lungs, 1-3 days skin bluish to black from hemorrhage and lack of oxygen (black death). Disease communicable among humans through respiratory route. Mortality virtually 100% within few days if no early treatment. Diagnosis: patient sample from bubo or blood, gram negative coccobacillus. Direct smear reacted with lab antibody. Rapid dipstick for field testing, measures blood reaction with lab antibody. Treat: lance/drain buboes, streptomycin, doxycycline, other antimicrobials. Treatment effective if given early enough but might not be diagnosed on time. Prevent: surveillance dead rodents in endemic areas, post warning, inspect ships for rats to prevent transport to new area, rat guards on mooring ropes. Positive animals, rodent extermination in residential areas. Educate tourists not to feed squirrels and chipmunks from hand. Insect repellant outdoors in endemic area, prophylactic antimicrobial after probable exposure, vaccinate people in high risk occupations. Plague in US West of Montana, Wyoming, Colorado. Bacterial systemic. Bubomic, septicemic, pneumonic. 1980s praire dog and rock squirrel epizootics with 40 cases, generally less than 20. No mostly in middle/Southern Africa and Madagascar, 100 to over 10,000.

Rheumatic fever

sequela chronic condition with different pathogenesis from acute disease 2-3 weeks after onset of acute infection, occur in <3% of strep. Rheumatic Fever: sequela to strep, antibody produced to M protein cross reacts components of heart muscle, damages heart, especially valves. Similarity of antibody affinity called molecular mimicry, considered autoimmune. Early penicillin treatment serves as secondary prevention of rheumatic fever and glomerulonephritis. Once sequela developed, too late to treat with antimicrobials. Upper

Not zoonotic

smallpox from camelpox, measles from cattle, TB from M bovis, HIV from SIV. Exclusively human