MMI To Know (Master Doc)

Bacteria to Know A. Gram positive cocci (purple-blue spheres in clusters, pairs or chains) Staphylococcus sp. ● Facultative Gram positive cocci in clusters ○ Non-motile, non spore forming, capsules ○ Divided into three groups on the basis of their hemolytic reactions on blood agar: ■ alpha hemolytic (green colour) ■ beta hemolytic (total clearing of blood cells on blood agar) ■ gamma hemolytic (no change) Grouping of hemolytic streptococci based on cell wall carbohydrates (Landsfield typing) ● Beta hemolysis: ○ Group A: S. pyogenes ○ Group B: S. agalactiae ● Alpha, gamma and variable hemolysis: ○ Group C: Several strains, clinical significance? ○ Group D: (enterococci also known as S. faecalis) ○ Group G: several strains, clinical significance? Staphylococcus aureus (coagulase +) ● G+ cocci ● Primary pathogen ● Can be grown on artificial media, possess machinery for production of own energy ● 27-30 mins generation time ● Coagulase is an enzyme is usually used to differentiate S. aureus from S. epidermidis ● Pyogenic (pus-producing) bacteria ● Produce coagulase - fibrin clots to form around bacteria (differentiating characteristic from other staph species) ○ Converts fibrinogen (sol) to fibrin (insol): “coagulase positive staphylococci” ○ Walls off the source of bacteria with the protein so the WBC cannot get at them ● Often yellowish colonies on BAP “yellow or golden staphylococci” ● Produce coagulase ○ MSSA (methicillin susceptible S. aureus) ○ MRSA (methicillin resistant S. aureus) ● Common cause of food poisining, nosocomial infections, and skin and wound infections Some Virulence Factors (break apart tissue very easily) ● Coagulase ● Adhesion molecules ● Exotoxins and superantigens ● DNase (break down DNA) ● Membrane damaging toxins (e.g. leucocidin) ● Capsule (sometimes) ● Protein A (Fc receptor) Impetigo ● Often in newborns and young children, caused by: Staphylococci and Streptococci ● Infection of epidermal layer - superficial infection of skin and is very infectious in children due to their play behaviour and the amount of skin to skin contact they have ● Treatment: removal of crusts, washing of lesions and application of topical antibiotics, washing the sores with soap and water ● Oral antibiotics only if infection spreads Toxic Shock Syndrome ● Life threatening, multi-system effects ● Fever, vomiting, sunburn-like rash ● Effect of a “superantigen” ● Often the exotoxin causing this is TSST-1 (toxic shock syndrome toxin-1) ○ TSST-1 toxin binds unspecifically to TCR and MHC II ○ Consequence of unspecific binding to TCR and MHC II is the activation of most T helper cells ● First identified in association with tampon use, now most common in patients following surgery, and intravenous drug abusers (nasal surgery - common in surgery) ● Can also be caused by GAS (group A streptococcus = S. pyogenes) ● Treatment: IV antibiotic (usually semisynthetic penicillin like oxacillin) - treat with intravenons antibody Scalded skin syndrome ● Neonatal or 2° to toxic shock syndrome - due to S. aureus exfoliative toxin ● Often begins as skin lesion exfoliative toxin affects the junctions of epidermal cells and causes loosening of cells ● Treatment: IV antibiotic Staphylococcus epidermidis (coagulase -) ● Opportunistic ● G+ cocci ● Constitutes the bulk of the normal flora on the skin Staphylococcus saphrophyticus (coagulase -) ● Primary pathogen in the urinary tract, young women ● Gram+ cocci Staphlyococcus pneumoniae (diplococci not long chains) (LRTI) ● Alpha hemolytic ● Very high mortality rate, more common in children but can affect any age ● Most common bacterial cause of meningitis in the elderly ● Often acute onset ● From 20% to 30% mortality even in treated cases ● ● On lung x-ray, a Ghon complex is found Type of bacterial meningitis with the highest complication rate, 15% to 20% sequelae in treated cases ● Has capsule and produces IgA protease; very good at inducing inflammation ○ Inactivates complement and prevents opsonization and phagocytosis ● Vaccines available ○ Adults: vaccine to polysaccharide capsular antigens and/or the conjugated vaccine ○ Children: conjugated vaccine only ● Emerging resistance to penicillin due to genetic mutations in PBP (penicillin-binding protein) ● Pathogenicity ○ Many virulence factors ■ Capsule: >90 antigenic types - main virulence factor ■ Cell wall: lipoteichoic acids and peptidoglycan ■ Choline binding proteins for host cell attachment ■ Autolysins : self-destruction (bacteria makes it, kills bacteria, setting up stage for larger infection), releases other chemicals. ○ Pneumolysins: damage pneumocytes in lungs ○ Production of hydrogen peroxide, neuraminidase and IgA protease ● Risk Factors ○ Astha, cystic fibrosis, chronic obstructive pulmonary disease (COPD), weakened immune system (HIV, cancer….), young children and elderly Pneumonia (or pneumonitis) ● Typical: classically caused by S. pneuoniae responds to penicillin treatment ● Atypical: caused by other organisms, penicillin resistant, includes virus, bacteria and fungi ○ Most common cause of infection-related death globally ● Causes in adults and children different ○ Adult: mainly bacterial ○ Children: mainly viral ● “Old Man’s Friend” is a common infection that can be life threatening for older individuals due to the blockage of oxygen transfer in the alveoli due to the infection with mucs and pus (sputum) consolidating lungs. The alveoli have intimate contact with the blood circulation, since this is where oxygen transfer from lungs to blood happens, and it is easy for bacteria in the lungs to translocate to the blood. Since it is encapsulated, in a non-immune person, the bacteria will have at least a week or more to growth and spread in the blood before antibodies are produced to facilitate opsonization, phagocytosis and killing of the bacteria “Pneumococcal” Pneumonia (Typical) ● “Pneumococcal” Pneumonia (Typical) ● Encapsulated facultatively anaerobic Gram positive diplococci – Streptococcus pneumoniae (nickname: pneumococcus) ● Most common cause of pneumonia, involves alveoli and bronchi ● Symptoms: fever, rust coloured sputum (blood), breathing problems and chest pain ● Often spreads to the blood (bacteremia - septicemia - sepsis) ● Vaccines ○ Polysaccharide (23 types) ○ Conjugate (21 types) Viral causes of LRTI (atypical pneumonia) Bronchiolitis in infants ● Usually after an upper respiratory tract infection ● Disease restricted to children usually < 2 years ● Bronchioles of children very small (diameter) - if the cells lining them are inflamed and swollen the passage of air to and from alveoli is reduced ● Necrosis of epithelial cells (spread to the lung → interstitial pneumonia) ● 75% of cases caused by RSV Streptococcus pyogenes (URTI) ● Beta hemolytic - Group A strep or “GAS” ○ Important pathogen in skin infections, M protein important for attachment (infect tissues), hold macrophages away from bacteria, kind of like a superantigen effect ■ Pharyngitis, tonsillitis ■ Impetigo ■ Cellulitis (bacterial infection in dermis), erysipelas ■ ”childbed fever” ■ Necrotizing fasciitis (flesh eating disease) ○ Post-infectious disease: ■ Acute glomerulonephritis (affect kidney) ■ Rheumatic fever (affect heart valves) ● Pyogenic (pus-producing) bacteria ● Strep throat (Streptococcal pharyngitis) ○ The most common etiological agent of pharyngitis is virus ○ On inspection, strep throat cannot be differentiated from any other type of infection laboratory tests necessary!!! ○ Rapid tests are available but if the test is negative and the suspicion continues send a swab to the lab! ○ Need to treat all cases of Streptococcus pyogenes pharyngitis with antibiotics to prevent sequalae (complications coming after an infection) Scarlet Fever ● S. pyogenes can produce an erythrogenic toxin: ○ Only strings of S. pyogenes producing the exotoxin (a superantigen) can cause scarlet fever ○ The first time you get Strep throat with one of these strains producing this superantigen toxin ○ There is only one type and immunity to it is attained after one bout of SF ○ Pinkish-red sandpaper like skin rash ○ High fever ○ Strawberry tongue (loses upper membrane, becomes inflamed) ○ Scarlet fever varies in severity, may progress to glomerulonephritis or rheumatic fever Rheumatic Fever ● Non-infectious complication of a S. pyogenes infection occurring after an infection has disappeared ● Cross reactivity of bacterial antigens with tissue antigens. Several different antigens involved… ● Some evidence for T lymphocyte invasion in addition to neutrophil damage ● Most often mitral valve damage ● Some of the antibiotics react with some of our body substances, like myosin in the heart, antibodies that bind it the myosin in heart (immune complex); activated by classical pathway — > C58 (send help to neutrophils to come to area to help with so called infection), degranulate and causes tissue damage ● A late complication of pharyngitis with Group A strepto-cocci Streptococcal toxins and enzymes ● Streptokinase (dissolves blood clots - breaks down fibrin) ● Hyaluronidase (breaks down connective tissue) ● Deoxyribonucleases (degrade DNA) ● Proteases (e.g. IgA protease) ● Erythrogenic (red) toxin (rash of Scarlet Fever - continuation of a strep infection that was not treated properly) (superantigen) ● Spe toxins (superantigens sometimes present in NF strains, are exotoxins that cause massive tissue damage and inflammation, like Flesh Eating Disease) ETC. Erysipelas ● Infection of the dermal layer of skin ● Can progress to septicemia and fatal outcome ● Can begin as a pharyngitis ● Treatment: antibiotic Streptococcal impetigo ● Treatment: removal of crusts, gentle washing and topical antibiotics Necrotizing fasciitis (flesh eating disease) - caused by S. pyogenes or GAS ● 24 year old woman is admitted for liposuction ● Develops high fever and extreme pain in the area within 1 day of surgery ● Sore starts to weep, become inflamed and edematous (swollen) ● Sepsis develops – source found to be the surgical area ● Patient given antibiotics and sent to exploratory surgery ● Massive tissue damage found, cultures and Gram smears done, finding of Gram positive cocci in chains and growth of beta-hemolytic streptococci on blood agar plates ● SpeA toxin detected in bacterial isolate (superAg) ● Transmitted by direct contact Diagnostic symptom is disproportionate pain to injury!!!! ● Ex. pimple but in extreme pain (you cannot move body) ● Extremely rapid progressive infection ● ● ● ● Streptococci invade deep and destroy the fascia (muscle sheath) liquifying the tissues as it progresses Mortality >40% even with timely treatment Very important with quick diagnosis, debridement of necrotic tissue and antibiotics Cardial symptom of necrotizing fasciitis Streptococcus agalactiae ● Beta hemolytic - Group B strep ● Bacteria usually acquired at birth from the mother ● Fifty percent mortality in neonates ● Most common organism causing neonatal meningitis ● Difficult to diagnose meningitis in an infant; signs are poor feeding, lethargy, vomiting, diarrhea, respiratory distress, sometimes bulging fontanelle ● Complications severe in those who survive Approximately 30% have cerebral or cranial nerve palsy, epilepsy, mental delays, hydrocephalus B. Gram positive bacilli (purple-blue rods) Listeria monocytogenes ● Gram positive bacillus, non-spore forming, psychrotroph ● Facultatively anaerobic, motile (has flagella) ● Grow well on complex media (BAP - blood agar plate) ● Grow wide temp. range (3 - 42 C), wide pH (≤5.5 - 9.5) - pH tolerant, high concentrations of NaCl (up to 10%) ● Normal habitat: widely distributed in nature, grasses, soil is probably the natural reservoir, animal intestine through contaminated feed, hardy: survives in low temperatures, high acidity, and salt concentrations ● Causes in man (food borne disease, CNS infections/death, abortion) and animals (CNS infections, goats, cattle, “circling disease”, septic abortion) ● Transmission: fecal-oral (food contaminated with animal feces), foods such as coleslaw, soft unpasteurized cheeses, turkey winners, cold cuts, mushrooms, milk, prepackaged salads ● Virulence: gene ActA codes for "invasin", listerolysin, phospholipases ● Pathogenicity ○ invasion of bacteria through gastric epithelial cells (rearrangement of actin propels bacteria from one cell through the next cell membrane into another cell like a rocket) gene ActA ○ Grows in macrophages, destroys phagolysosome (membrane bound compartment that the bacteria are taken into the cell in) with listeriolysin (breaks open vacuoles containing bacteria in eukaryotic cells (ex. macrophages), releasing bacteria into the cytoplasm ○ Produces two other hemolysins (phospholipases) that destroy cell membrane ○ Intracellular and extracellular growth ● ● ● ● Prevention/Treatment ○ No vaccine ○ Antibiotics for treatment if diagnosed in time Clinical infection ○ Meningitis, encephalitis (brain tissue inflammation), septicemia ○ Incubation period may be longer than 2 months ○ Mortality of CNS infections 20-50% (difficult to diagnose this type of meningitis) ○ Pregnant women (influenza-like bacteremia illness that can result in abortion or stillbirth) Epidemiology ○ Hard to track because of long incubation period and underreporting ○ Estimated to be responsible for ~1700 cases of invasive disease in the US each year (huge) ○ Fatal in about ⅓ cases even with appropriate treatment ○ Maple Leaf incident Salt is used to create a hypertonic environment in which water is drawn out of bacterial cells through osmosis. The loss of water can dehydrate and damage the bacterial cells, inhibiting their growth and multiplication Corynebacterium diphtheriae (without spores) (URTI) ● Pathogenic strains produce exotoxins that diffuse through tissues, cause death of epithelial cells in the throat and affect nerves (e.g. in heart and face) ● Result: ○ Inflammation → accumulation of phagocytes ● Typical thick gray membrane (pseudomembrane): ○ Covers back of throat – very hard to remove, grows out of the tissue and bleeds if you try to dislodge it ○ Can prevent breathing, obstructs air passage ○ Bacterium attaches to the tissues, where they may produce an exotoxin that inhibits protein synthesis in host cells and causes cell death ○ Composed of dead host cells, neutrophils (alive and dead), fibrin and bacterial cells. This membrane is firmly attached to the throat but may loosen and get aspirated to the bronchioles in the lungs, blocking oxygen to alveoli ● Apathogenic unless lysogenized (transduced) by a bacteriophage which transfers the exotoxin gene ● All isolates of this bacteria must be tested for toxin production ● Effects of toxin: myocarditis, cardiac failure, polyneuritis, death (toxin has an affinity for nerve cells) ● Bacteria do not invade tissues, just expel exotoxin which can diffuse into other areas ● Cutaneous diphtheria: common in tropics Diphtheria ● Caused by Corynebacterium diphtheriae (serious disease), an aerobic Gram positive bacillus ● ● ● ● ● ● ● ● (non-spore forming) ○ Toxin mediated disease, if they DO NOT have the gene for the exotoxin (violence factor), they do DO NOT cause the disease ○ If you isolate a starin that does not produce toxin → is not pathogenic Bacteria do not invade tissues - they produce an exotoxin (inhibits protein synthesis in host cells - tropism for nerve cells), which diffuses into tissues, inhibits protein synthesis and is neurotropic ○ Epithelial cells of the throat, stay on the outside of the cells and produce exotoxin that can migrate through the tissue into the bloodstream like the heart (facial paralysis, nerve damage) Once leading cause of mortality in children (9,000 cases in children 1-5 yrs in the early 1920’s) Toxoid vaccine introduced in 1924 - it is not the bacteria that is being targeted, it is the exotoxin Vaccination has drastically reduced the incidence of disease in North America and Europe – now it is a rare disease here Symptoms: ○ Sore throat, fever, malaise (general weakness, nausea) ○ Neck swelling (“bull neck”) ○ Nerve paralysis (can have heart dysfunction) ○ White-gray membrane across back of throat (fibrin, dead tissue, bacterial cells, toxin and neutrophils) Pathogenicity ○ Apathogenic unless the bacterial strain has been “lysogenized” or “transduced,” meaning the organism is infected with a specific bacteriophage with a gene encoding for the toxin ○ White–gray membrane across back of throat (composed of fibrin, dead tissue cells, leucocytes, and bacterial cells) ○ Three types of bacterial subspecies ■ C. diphtheriae gravis ■ C. diphtheriae mitis ■ C. diphtheriae intermedius ○ All types can be apathogenic or pathogenic ○ All isolates of C. diphtheriae must be tested for toxin production ○ Effects of toxin ■ Myocarditis, Cardiac failure, Polyneuritis ○ Toxin interferes with protein synthesis in cells, especially nerve cells Treatment: antibiotics and antitoxin ○ You need to stop bacterial replication and also at the same time to neutralize the exotoxin that has not yet bound to cells. Once the exotoxin is bound it cannot be neutralized Vaccine: effective (but need boosters), but older people in population may only have effective protection in 20% of cases due to lack of boosters ○ Tetanus toxoid is usually combined with diphtheria toxoid & pertussis DTaP Bacillus anthracis (aerobic) ● Cause anthrax ● Principle pathogen of Bacillus species ● Large aerobic Gram positive bacillus with spores (exotoxin is the major damaging virulence factor) ○ Spores very hardy - >50 yrs ● Disease of herbivores ● Found in soil and on vegetation ● NO human to human transmission Three routes of infection for humans ● Inoculation (most common) ○ Usually acquired by contact with animals or animal hides ○ Direct contact with skin, need skin break for organism to get in and cause problems can cause sores, not an extremely serious type of infection ● Inhalation (e.g. bioterror event in US 2002?) ○ Not common in present time, historically “woolsorters” disease (workers breathe this) ● Ingestion ○ Common in carnivorous animals, also found in outbreaks in Africa usually due to ingestion of contaminated meat Pathogenesis ● Plasmids responsible for acquisition of virulence factors: ○ pX01 for toxins and pX02 for capsule ● Polypeptide capsule (glutamic acid) - antiphagocytic (acts the same way as amino acid capsule) ● Inert nonmetabolizing spores germinate to growing “vegetative”bacteria when conditions are right ● Growth of bacteria leads to production of toxin (the spore do not produce toxin, the growing bacteria procures toxin because they are the one that have metabolism) ● 3 components of toxin ○ PA (protective antigen) - binding component ○ LF (lethal factor) ○ EF(edema factor) ● Must have PA and either LF or EF for toxicity Treatment ● Must be started early ● Penicillin is the “drug of choice” but ciprofloxacin used if resistance suspected ● Susceptible to many antibiotics: ○ pen, cipro, tetra, macrolides, clinda, chloro Immunity and Vaccines ● Some animal species are naturally resistant to anthrax ● Vaccines are based on attenuated organisms, or toxins from culture filtrates ● Human vaccine is based on the capsule, poor antigenicity (no good vaccine for humans) ● Animal vaccines good for controlling disease in animals Clostridium difficile (anaerobic) ● Strict anaerobe, Gram-positive bacillus, spore forming (endospores) ○ Spores are not “living”, survive months in environment, not inactivated by antibiotics, alcohols, or alcohol based hand cleansers ● A major cause of nosocomial infection (hospital acquired infection) globally ● Transmission: fecal-oral, contamination of inanimate objects (fomites)? ● Virulence: TcdA (toxin A), TcdB (ToxinB), CDT-C. difficile binary toxin ● Pathogenicity ○ Spores are infected and unaffected by stomach acid ○ Germinate in interesting after contact with bile acids ○ Exotoxins made by vegetative bacteria damage intestinal mucosa, kill cells, and cause epithelium to leak leading to watery diarrhea (both are cytotoxins) ● Syndromes ○ Dehydration ○ Diseases ■ AAD (antibiotic associated diarrhea) ■ AAC (antibiotic associated colitis) - inflammation in intestine ■ CDAD (clostridium difficile associated diarrhea) - diarrhea ■ TPMC (pseudomembranous colitis) ■ Toxic megacolon (gangrene of intestines) - green of intestines ■ Death ○ Children < 2 years never have symptomatic infection but may harbour the bacterium ● Treatment To prevent infections in the hospitals, a Sporicidal disinfectant should be used Conventional ● Antibiotics like vancomycin (target G+) and metronidazole (anaerobic) ● ● Unconventional ● Probiotics (minimal effect) ● Fecal implants (best success rate) Prevention ○ Avoid hospitalization ○ Keep environment clean (wash hands) ○ Reduce excess microbials ○ Restore flora ○ Vaccines or antibodies ○ Antibiotics and treatment Hypervirulent NAP1 strain more dangerous because it makes the endospore more resistant to disinfectants, produces extremely high amounts of toxin, and sporulates faster Clostridium botulinum ● Exotoxin producing ● Flaccid paralysis due to botulism toxin Clostridium perfringens ● Anaerobic, with spores ● Treatment (need all three): penicillin, clindamycin, metronidazole ● Causes gas gangrene Clostridium tetani ● Tetanus or “Lockjaw” (caused by the infection) ● Endospores are ubiquitous in soil ● Symptoms caused by a neurotoxin, tetanospasmin (bacteria do not invade and remain at the site of injury) ● Toxin enters the CNS via peripheral nerves or blood ● Tetanospasmin (toxin) blocks the inhibitory signals which normally stop the muscle contractions ● Death usually from spasms and spastic paralysis of respiratory muscles ● Vaccine good, part of the “DPT” ● Most of the cases in North America are in persons > 50 years due to lack of boosters ● Temporary protection against tetanus can be done in acute situations by administration of tetanus immune globulin (TIG) which will neutralize any free toxin. C. Gram negative cocci (pink-red spheres in clusters, pairs or chains) Neisseria meningitidis meningococcus (sing.) (pl. meningococci) ● Gram negative diplococcus (pink) with capsule (layers of sugar outside bacterial cell wall) ● Only affects humans: no animal reservoir ● One cause of meningitis and sepsis ● >12 serotypes based on capsule carbohydrates (polysaccharides or sugars) ○ Only 6 are responsible for most epidemics (A, B, W-135, X, Y) ● Transmission: droplet (coughs, sneezes, saliva) ~1 ● Virulence: capsules, endotoxin (has Lipid A of the LOS molecule), pili, IgA protease ● Pathogenicity ○ Attaches to epithelial cells in the throat ○ Invades and can go to bloodstream and/or CSF ○ Endotoxin activates blood clotting, leads to DIC (disseminated intravascular coagulation), hemorrhage (petechiae, purpura) and shock ○ Bacteria evade phagocytosis (being eaten) by WBC due to presence of polysaccharide coating around the outside of the bacterial cell wall - “capsule” ● Most severe cases: Waterhouse–Friderichsen syndrome with bleeding into the brain and adrenal glands Two types of diseases Meningococcal meningitis (inflammation/infection of the meninges) ● Increased pressure to brain, influx of inflammatory cells (WBC) to CSF Meningococcal septicemia/sepsis (replication/infection of bacteria in bloodstream) ● Disseminated infection (occur quickly), Gsepsis, intravascular coagulation ● Need for amputation in serious cases 90-95% chance of survival if diagnosed and treated early Death if untreated - if treated early has good prognosis ● Symptoms and Disease Meningitis: headache, stiff neck, photosensitivity, nausea, sore throat, petechiae, finally coma and eventual detail Sepsis: fever, petechiae/purpura, shock, hemorrhage, DIC - internal organ meltdown and eventual death Diagnosis 1. Aspirate CSF and/or blood 2. Gram stain CSF 3. Report to physician 4. Culture and/or EIA (enzyme immunoassay) or PCR (polymerase chain reaction) 5. Ascertain susceptibility to antibiotics ● ● ● Also: Serogroup for epidemiology (public leath) Treatment ○ Administer antibiotics after taking culture specimens ○ Empirical antibiotic treatment: best guess before culture confirmation ■ Best to use third generation cephalosporin (ex. ceftriaxone - good CSF penetration) ○ Antibiotic susceptibility testing will be done on bacterial isolate growing from cultures Vaccine ○ Polysaccharide (use capsule material as vaccine) ■ Effective against 4/15 types (A, C, Y, W135) ■ 90% protection for 2-5 years ■ Cannot be used for pediatric patients, < 2 yrs ○ Conjugated ■ Polysaccharide combined with protein ■ Good for children <2 yr and immunosuppressed individuals who cannot make antibodies efficiently ■ Serogroups A, C, W, Y ■ Used the most because of immune response ○ Type B vaccine ■ Based on proteins in cell wall NOT capsule polysaccharide Public Health Issues ● Rapid ID of disease ● Rapid ID of contacts ● Prophylactic (preventative) antibiotics ● Vaccination of susceptible individuals ● Health prevention information ● Reportable disease D. Gram negative bacilli ((pink-red rods)-short, long, fat, thin, curved, straight) Escherichia coli (including O157:H7) ● Aerobic and facultative ● 15-20 mins generation time ● Produce folic acid we can use (there is good and bad ones) ● EHEC (O157:H7), EPEC, ETEC, etc. ● Some have gained virulence factors along the way, but for the most part E. coli is pretty harmless Pseudomonas aeruginosa ● “Opportunistic pathogens” - normal inhabitant soil and water ● Can live in liquid soaps, water (tap water), soil ● Cause hot tub dermatitis ● Needs few nutrients, can infect many body sites ● Very common in burn patients and patients with cystic fibrosis ● Has endotoxin, produces exotoxins ○ Exotoxins - proteins that are released from the microbes that negatively affect host cells ● Sometimes grow in quaternary ammonium compounds used for disinfection Haemophilus influenzae ● Aerobic and facultative ● In order to cultivate bacteria needs hemin (from blood) and NAD (from yeast extract) ● Serotype b most common cause of meningitis in children <5yrs, pre-vaccine ● Infants 4 months protected by maternal antibodies, but these disappear, and there is a window of susceptibility until they produce their own IgG antibodies to the organism ● Onset usually insidious (days) ● Virulence factors: capsule, IgA protease, pili, endotoxin, OMPs (outer membrane proteins) ● Five percent mortality in treated cases but 9% with sequelae Bordetella pertussis Whooping cough (100 days cough) (URTI) ● The tracheal cytotoxin inhibits DNA synthesis in ciliated cells and causes death of the cilia. If ● ● ● ● ● ● ● ● ● ● ● there is damage to cilia, the ciliary escalator will not function and mucus cannot be coughed up and out of the respiratory tract, resulting in a paroxysmal coughing as the infected person tries to clear the mucus to allow oxygen into the lungs. It takes about 3 months for the ciliated cells to regen-erate; symptoms last until the system returns to normal. Aerobic and facultative Produces virulence factors that fuse up and can impact systemically. etc. cannot pull mucus up Produces many exotoxins Does not invade tissues, colonizes ciliated, respiratory epithelium and kills cells with tracheal cytotoxin Transmission: droplet Three stages of disease: ○ Catarrhal: cold like (running nose) ■ The state of infection is the most infectious stage; resembles a common cold ○ Paroxysmal: gasping cough (fits of coughing - last for about 3 months) ■ Tracheal cytotoxin causes this state of whopping cough ○ Convalescence: healing (still a little bit of cough but feeling better) Infants most at risk for: ○ Broken ribs ○ Pertussis pneumonia ○ Oxygen deprivation to brain In countries where there is no vaccination program, this is an important cause of morbidity in children Pathogenicity ○ FTA filamentous hemagglutinin (for adherence) ○ Pertussis toxin ■ Systemic effects ■ Diffuse in tissue in the bloodstream, activate macrophages (produce cytokines these diffuse to the brain temperature center) ○ Tracheal cytotoxin: damages ciliated cells (breakdown product of peptidoglycan) ○ Lethal toxin: tissue necrosis ○ Adenylate cyclase: reduces phagocytic activity ○ LPS Treatment ○ Treatment usually not effective for disease but reduces infectivity ○ Ex. erythromycin Vaccine ○ New acellular vaccine (against toxins) ■ Does not have any bacterial cells, composed of virulence factors ○ Combined with tetanus and diphtheria DTaP ○ 5 doses, new recommendations for revaccinating in early teens (need to get boosters) E. Other Important Human Bacterial Pathogens Mycobacterium tuberculosis (M. tuberculosis, MDR-TB, XDR-TB, MTB) (LRTI) ● Causes TB ● Cell wall has peptidoglycan but large amounts of mycolic acid which prevent stain penetration ● Facultative intracellular organism (can invade and grow inside or outside of host cells) ● 16-24 hours generation time ● Use a tuberculocidal agent to kill Mycobacterium ● Bacteria usually acquired at birth from the mother ● Fifty percent mortality in neonates ● Most common organism causing neonatal meningitis ● Difficult to diagnose meningitis in an infant; signs are poor feeding, lethargy, vomiting, diarrhea, respiratory distress, sometimes bulging fontanelle ● Complications severe in those who survive ● Approximately 30% have cerebral or cranial nerve palsy, epilepsy, mental delays, hydrocephalus ● MDR-TB: multidrug-resistant TB: organism is resistant to isoniazid and rifampin by definition XDR-TB: extensively drug-resistant TB: resistant to isoniazid and rifampicin and also any member of the quinolone family and at least one of the injectable drugs (like aminoglycosides) ○ Normally only first-line drugs used; patient becomes noninfectious in about two weeks ● Production of cord factor (causes bacteria to clump together and inhibits phagocytosis): this chemical is also toxic to host cells Tuberculosis ● Leading cause of death worldwide from bacterial disease ● Capable of intracellular survival & growth in macrophages (facultatively intracellular) - grow inside and outside of host cells ● No toxin produced. Inflammation- major pathogenic mechanism ● Transmission: airborne, droplet, direct or indirect contact, food (vehicle transmission) ● Bacillus, non-motile, acid fast, strict aerobe (like to grow in upper parts of lungs (oxygen), can grow in clumps ● Mycolic acid forms an impermeable barrier to entry of molecules into the bacillus ● Survive long period on dry surfaces ● Not visible in Gram stain (mycolic acid prevents Gram stain from entering the cell wall) ● Stained with Ziehl-Neelsen (acid fast) stain ● Many latent infections ● CMI usually controls infection but is also responsible for the pathology of the disease ○ CMI = cell mediated immunity (adaptive system) make granulomas (hold infection) After TB Exposure ● Three things could happen 1. Latent infection where few TB organisms enter macrophages and remain latent there 2. Primary tubercle (granuloma - can form in lungs) forms but the immune system - can stop replication 3. Spread of active infection – this happens in immunocompromised individuals Primary Infection: often in lung ● Host walls off the infection in a “tubercle” (a granuloma) ● Tubercule: ○ Macrophage, B and T cell collection with central caseation, TB cannot replicate because of the low pH and low oxygen ● Disseminated infection occurs if the tubercle does not form, or forms but ruptures and the bacteria spread to the blood and lymph systems – this is then a disseminated infection called “miliary tuberculosis” (refers to the small granuloma) ● Glon Complex Second Stage Infection ● “miliary” infection ● Directly spread from1° infection OR reactivation of a latent infection ● Characterized by spread of tubercles (granulomas) ● You can get TB anywhere in the body! ● Symptoms: ○ Weight loss, fever, night sweats, chronic cough, coughing up blood, lethargia (consumption) TB Infection versus TB disease (latent vs active) ● ● ● ● ● ● ● TB Infection (latent) MTB present Tuberculin skin test positive (test for memory cells) Chest x-ray normal Sputum (breathe in some water latent air - irritation to lungs) smears and cultures negative No symptoms Not infectious Not defined as a case of TB ● ● ● ● ● ● ● TB disease (active)(in lungs) MTB Present Tuberculin skin test positive Chest x-ray usually reveals lesion Sputum smears and cultures positive Symptoms: cough, fever, weight loss Often infectious before treatment Defined as a case of TB Risk factors for Clinical Tuberculosis ● Presence of another infection, e.g. HIV (knocks down adaptive immune system) ● Physiological and environmental stress ○ Malnutrition, etc ● Depressions of the immune system e.g. older age Laboratory Diagnosis ● Acid-fast rods in sputum if it is active ● ● ● ● ● Culture (takes up to 6 weeks for a negative result, positive cultures usually grow in 2-3 weeks) QuantiFERON Gold – blood sample, tests if T lymphs are activated to M. tuberculosis (measures interferon levels produced) Skin Tests for Tuberculosis ○ Tests cell-mediated/acquired immunity by detection of memory Tuberculin Test used as screening test for disease: ○ PPD (purified protein derivative) intracutaneously ○ Measuring the diameter of the induration ○ Delayed hypersensitivity reaction measured Mantoux test ○ Quantitative tuberculin test Vaccine ● BCG: Bacillus Calmette-Guerin ○ Live culture of Mycobacterium bovis ○ In North America only given to children at high risk ○ The effectiveness of the vaccine is not very good and it doesn’t last very long! ○ Adults – almost no effect, children some effect Treatment and antibiotic resistance ● Multiple drug regimens used to prevent development of drug resistance ● Treatment 6 mo – 1 yr because of slow growth of the bacterium ● MDR-TB and XDR-TB is a growing problem ● MDR-TB resistant to isoniazid and rifampicin (first line drugs) ● XDR-TB resistant to first and second line drugs ● Isolation and Quarantine Mycobacterium leprae ● Cell wall not stainable using Gram stain ● 2 weeks generation time Mycoplasma pneumoniae (M. pneumoniae) ● Causes pneumonia ● No cell wall and no peptidoglycan; contains large amounts of sterols Atypical Bacterial Pneumonia ● Very small organisms, cannot stain with Gram’s stain (because there is no cell wall) (genetically belong to Gram positives) ● Causes “walking pneumonia,” pneumonia that looks terrible on an X-ray, but the person is still walk-ing and behaving relatively normal ● Can be responsible for 15%–40% of pneumonia, depending on the year and situation ● Often affects school-aged children and teenagers ● P1 protein on organism responsible for adhesion (virulence factor) ● Can cause neurological complications ● Symptoms: Low-grade fever, cough, headache; may have erythema (skin manifestations ● ● Diagnosis: Serology, PCR (culture very difficult) Treatment: Tetracyclines, macrolides, no vaccine available Treponema pallidum ● Slower type of disease ● Too small to see in Gram stain Chlamydia trachomatis ● Causes chlamydia ● Intracellular pathogen too small to see ● Lack enzymes for ATP production ● Usually cannot be grown in the laboratory on artificial culture media ● The more times you have it, the more damage you have to your eyes Ocular ● Types A-C ● Trachoma is a disease caused by C. trachomatis A-C ● The infectious disease commonly causing blindness Genital ● If you change your tampon and do not wash hands and touch eyes ● Types D – K, LGV ○ *Note that you can infect your eye with a genital Chlamydia, but then it is not called trachoma but rather “inclusion conjunctivitis” Parasites to Know Protozoa Entamoeba histolytica ● Agent of amoebic dysentery (severe diarrhea) ● Primary food: RBC - ulcer (flask shaped) formation & bloody diarrhea ● BOTH trophozoite and cyst forms exist ● *Cyst high degree of resistance to chlorine ● Treatment: nitroimidazole, metronidazole (Flagyl) Giardia lamblia ● Flagellate (swim in aq and non aq); causative agent of giardiasis, “beaver fever” ● Can get it from inadequately treated river water ● Intestinal upsets, flatulence (extreme gas production), nausea, abdominal cramps, diarrhea ● BOTH trophozoite and cyst form ● *Cyst hardy, resistance to chlorine ○ Resistant to the chlorine concentrations in normal drinking water ● Treatment: nitroamidazoles (inhibits the anaerobic metabolism of both bacteria and parasites) Trichomonas vaginalis “Trich” ● Flagellate, motile ● NO cyst stage, person to person infection - transmission sexual ● Found in vagina and male urethra ● Intense itching, inflammation of tissues Acanthamoeba species ● Grows in water, exists as cyst form in DUST ○ Can be considered an opportunist, find the cyst form in water, soi, and dust ● BOTH cyst and trophozoite stage in HUMANS ● Important for contact lens wearers ○ Often contact lens weaters can have micro-abrasions on the surface of their corneas and if they dust or water containing the amoeba is able to enter the scratches, then can invade deeper into the cornea and the eye, causing inflammation and scarring that result in blindness ● Eye loss outcome of infection Acanthamoeba castellani ● Known to cause infections resulting in blindness Cryptosporidium parvum ● Cows, rats, dogs, cats - to people ● Chronic diarrhea, severe in immunocompromised or immunocompetent ● Transmission: water ● Use acid-fast stain to detect ● **oocysts have high resistance to chlorine ● No good treatment Toxoplasma gondii ● Life cycle in cats - cat feces contain oocysts ● Oocysts ingested by humans or animals ● Tissue cysts containing the protozoan can form in other animals ● Acquired from uncooked meats (tissue cysts) or form contact with cat feces (oocytes) ● Serious for fetus in pregnancy (especially first trimester) Trypanosoma ● Blood parasites, transmission mainly vectors (bugs) ● T. brucei gambiense/rhodesiense ○ Causes African Sleeping Sickness (tsetse fly) ● T. cruzi ○ Causes Chaga's disease (reduviid/kissing bug) Leishmania species ● ~20 different species transmitted by sand fly vector ● Visceral (most severe - all over body), cutaneous (least), and mutocutaneous syndromes ● Develop and grow in macrophages Plasmodium species - 4 types ● Causes malaria, no vaccine ● Transmitted by Anopheles mosquito ● Mosquito carries the sporozoite in saliva which reaches the LIVER within 30 min ● 4 main types ○ ○ ○ ○ P. falciparum (most dangerous) ■ Infects ALL ages of RBC ■ Fever and chills caused by toxic breakdown with RBCs rupture ■ Sequestration (sticky collections) of parasites and RBC occlude capillaries and cause organ death - Virulence factor PfEMP1 (a protein) ■ SEVERE Consequences - cerebral malaria (clumping and occlusion of blood vessels, also vasculitis), anemia (caused by lysis of RBC), and kidney failure (caused by high levels of hemoglobin breakdown products) P. malariae ■ Are hypnozoites - dormant or latent forms of the malaria parasite P. ovale ■ Hypnozoites P. Vivax ■ Latent stage in the liver Babesia microti ● Tick-borne protozoal infection, Ixodes sp. (same tick that carries Lyme disease) ● Common in northeastern United States ● Protozoa enter and replicate in RBC (red blood cells); resemble plasmodium; end result hemolysis and anemia ● Relatively mild to moderate disease Metazoa A. Nematodes (round) ● Roundworms with complete digestive system, including mouth, intestine, and anus Eggs are in the infective stage (2) Enterobius Vermicularis Pinworm ● Spends whole life cycle in human ● Lives in large intestine, females migrate to anus, lay eggs just outside of the anus ● Produces a glue (irritant) to stick the eggs to the skin ● Usually not serious but VERY INFECTIOUS (ex. daycare) - can cause hyperactivity ● Eggs are the infections stage and transmitted by direct contact with eggs or ingestion of eggs stirred up in dust ● To test it: a scotch tape specimen is taken and sent to the lab ● Treatment: over the counter anti-parasite tablets Ascaris lumbricoides ● Occurs in Alberta, untreated manure can spread this ● Large round worms (can resemble an earthworm) ● Lives in small intestine of pigs, cows, horses ● Eggs in soil very hardy (thick protein coat around egg) ● ● ● Adult worms distinct sexes (dioecious) Diagnosis by examination of feces Eggs hatch in intestine, larvae → lungs → trachea → nose or mouth (children) Larva are in the infective stage (4) Hookworms ● Infection by larvae, enter intact skin of bare feet ● -> lymph & circulatory system -> lungs -> coughed up and swallowed to small intestine, where they attach by hooks on the scolex (head) ● Acquired by walking barefoot in contaminated soil ● Suck blood, causes anemia ● Eggs excreted ● Only in warm climates Anisakis ● Fish nematodes, accidentally infect humans in larval form ● Rare infection, can get from eating sushi ● Prevent by heating (60C for 10 min) or blast-freeze (-35* for 15 hours, -23* for 7 days), OR cleaning of fish (evisceration) ASAP Trichinella spiralis ● Ingestion of encysted larvae in undercooked pork, bear, boar, walrus ● Larvae encyst in striated muscle fibers (and heart), encysting and weakening the muscle ● Dominant symptom is muscle weakness ● Difficult to treat Filaria - Blood Nematodes ● Lymphatic filariasis (elephantiasis) ○ Adult worms live in lymph tissue ● Onchocerciasis (river blindness) ○ Adult worms live in subcutaneous tissue ● Transmission by mosquitoes ● Microfilariae (offspring of adult worms) - circulate through bloodstream or migrate through subcutaneous tissue B. Trematodes (Flukes - leaf shaped) Flukes Schistosoma ● Human infected by cercariae (larval forms) that penetrate intact skin in freshwater ponds ● Adults hide from host immune system under a coat of protein acquired from host ● Worms reside in the venous plexus of bladder or intestine, depending on species ● Eggs cause iinflammation (NOT adult worms) ● THREE TYPES S. haematobium ● Urinary schistosomiasis (bilharzia) ● Inflammation of bladder wall , chronic sequelae - cancer S. japonicum ● Intestinal parasite S. mansoni ● Intestinal parasite ● Often in liver “Swimmers itch” ● Caused by duck schistosome ● Does NOT enter human circulation, self-limiting, causes skin itching due to immune response C. Cestodes (tape worms) ● Intestinal parasites, dependent on host for nutrients, no digestive system ● Head/scolex has suckers or hooks for attachment to gastric mucosa ● Body consists of segments called proglottids, each of which contains male and female productive organs ● Infections by humans: gastrointestinal route ● Acquired by eating inadequately cooked contaminated beef, pork, or fish ● TWO DISEASES ○ Intestinal infection: mild clinical picture, produced by pork, beef, fish, or rodent tapeworms ○ Deep tissue infection: serious infections, pork tapeworm (cysticercosis) or echinococcosis (dog tapeworm) Taenia saginata: beef tapeworm ● Life cycle requires both humans and cattle ● Infectious tissue larvae (cysticerci) ingested by humans in infested meat and mature into adult tapeworms in intestine ● Eggs passed in feces ● Usually mild symptoms ● Good for weight loss? Taenia solium: pork tapeworm ● WORST, more dangerous than beef tapeworm (cerebral cysts cause cysticercosis); person to person transmission is possible ● Life cycle involves both pigs and humans ● 2 modes of transmission: ○ Eggs: result in hatching of larva in intestine, which then escape and penetrate body tissues, including the brain (encyst in brain and cause fainting and seizures) ○ Larvae: result in adult worm in intestine Echinococcus granulosus: dog tapeworm ● Small tapeworm, humans are dead end hosts ● Dogs, coyotes, dingos ● Larva develops into a hydatid cyst with hundreds of worm parts but cannot form a whole tapeworm in humans D. Ectoparasites ● Live on skin, do NOT enter deep tissue ● Often results in secondary infections due to scratching Sarcoptes scabei ● LEAST HARMFUL ● Finger webs, elbows, armpits, breast, groin and buttocks: rarely on head ● Mites burrow into skin, feed, life span 30 days, mate, lay eggs in burrow ● Host defenses cause inflammation around the burrows, intense itching ● Secondary infections with skin bacteria ● Other sarcoptes mites to not thrive on humans and establish infection Pediculus humanus Head Lice ● Surface dwellers ● Penetrate skin with mouth, such blood ● Female glues eggs to hair shafts ● Eggs hatch in 5-10 days ● Secondary infections when lice feces are crushed into wounds Phthirus pubis Pubic Lice or “Crabs” CHECK ABOVE (Pediculus humanus) Others/Extras Dracunculus medinensis (Guinea worm) ● Fecal–oral transmission, the growing larvae penetrate the intestines and travel in the subcutaneous tissues ● Can be up to 1 m in length ● Emerge from body by causing a blister, which erupts and the worm emerges—when it senses water, it releases larvae into the water, perpetuating the cycle ● Treatment: usually removal of worm (slowly winding it out 1 inch/day so as not to break it and cause undue inflammation) ● Probably the origin of the snake winding around the staff in the medical symbol (rod of Asclepius) ● WHO has an eradication program, which has been successful, and the number of cases are drastically decreasing in Africa Trichuris trichuria “whipworm” ● Relatively benign infestation of children; found in tropical and subtropical countries; associated with rat feces ● Small, slender worm ● Usually asymptomatic Diphyllobothrium latum ● Fish tapeworm; ingestion of larvae in undercooked contaminated fish (Scandinavia, Pacific north-west in North America) ● Can get to 10 m in length; attach to intestinal wall with grooves on the scolex ● Use vitamin B12 and cause B12 deficiency—with megaloblastic anemia ● Mild to moderate symptoms, some diarrhea, abdominal pain ● Eggs are excreted in the feces Hymenolypsis nana ● Most common tapeworm globally, common in all tropical areas ● Small, 1–4 cm Fungi to Know Yeast = one celled fungi Candida albicans ● C. albicans is normal flora in the gut and mouth ● May attach to epithelial cells as a yeast, but invades deeper tissue by means of pseudohyphae ● Type of systemic mycoses (opportunistic pathogens) ● Causes vulvo-vaginal candidasis and thrush (occurs in newborns, immunocompromised and in people who have been treated with “broad spectrum antibiotics”) ● Has yeast outside the body Cryptococcus neoformans/gatti ● Produce a polysaccharide capsule ● Can cause meningitis or leukemia if immunocompromised ● Encapsulated yeast ● Associated with pigeon droppings ● Inhalation may cause only lung infection in immunocompetent but may disseminate in immunocompromised ● Treated with amphotericin B and flucytosine ● High mortality rate even in treated cases (30%) Malessezia furfur ● Type of superficial mycoses fungal infection ● Common cause = yeast Saccharomyces sp. ● Yeast that is used for baking, wine, leavening dough ○ Nonpathogenic ● Can cause significant infection if injected into the skin Molds = Many celled fungi Aspergillus species Aspergillosis ● Opportunistic pathogens, environmental fungus ● Infects people with debilitating lung diseases and immunocompromised ● Not a dimorphic fungi since it does not have a yeast stage ● Found in hospitals, everywhere in dust, in wood (construction sites) Dimorphic Fungi (primary pathogen?) Sporothrix schenkii Rose Gardener’s Disease ● Subcutaneous infection ● Fungal spores introduced into wound after trauma ● Lymphangitis common (usually arm or leg) - causes more ulcers as disease progresses ○ Inflammation of the walls of lymphatic vessels Histoplasma capsulatum ● Characteristic geographical location ○ Ohio river valley, Saint Lawrence river ● Spelunkers Disease Coccidioides immitis ● Characteristic geographical location ● Arizona, VERY infectious (dust storm) ● Valley Fever ● Cause LRTI Blastomyces dermatitidis ● Characteristic geographical location ● More of a range, gets into Manitoba, eastern US DNA Viruses to Know ● Papillomaviridae (HPV) ○ Papillomavirus is known to sometimes cause cancer ○ WARTS = human papillomavirus HPV ■ Cause callus with a black spot on his foot - plantars warts ● Adenoviridae (adenovirus) ○ Causes eye infections ● Hepadnaviridae (Hepatitis B virus) ● Herpesviridae (HSV-1, HSV-2, HHV-3) ○ HHV-3 is chicken pox (human herpesvirus - 3) “varicella” ○ “Provirus” ○ Herpes viruses - latency ○ Herpes simplex - causes cold sores ○ BOTH HPV and HSV transmitted through direct contact ● Poxviridae (smallpox (Variola major), monkeypox) ● Parvoviridae (B-19) ○ Only one infect humans, the rest infect dogs (extreme diarrhea), etc. Peter Ate His Huge Pot of Pie Chicken Pox ● Caused by enveloped DNA virus ● Acute infection ○ Fever, itchy (pruritic) rash (5 days) ○ Rash primarily on head on trunk, less on arms and legs ○ Airborne virus ○ Skin vesicles always present in different stages of formation ○ When healed, virus travels up nerve ganglion where it remains latent ● Latent infection ○ Virus is present but is not replicating until triggered by external factors, then travels down nerve to skin and reactivates ○ Reactivation is known as Shingles or Zoster (decline in immune system, exposed to UV light or stress) ○ Can cause permanent disability Complications - secondary bacterial infection ● Common in immunocompromised ○ Flesh-eating disease in children (chicken pox parties) ● CNS disease: encephalitis, meningitis, myelitis (uncommon) ○ Encephalitis: inflammation of active tissues of the brain ○ Meningitis: inflammation of the meninges (DISEASE NOT BACTERIUM) ○ Myelitis: inflammation of the spinal cord ○ Hemorrhagic complications (rare) ○ Primary varicella pneumonia (very rare but serious) Prevention of Chickenpox ● Active immunization (healthy individuals) ○ Live attenuated vaccine, highly protective, memory cells produced ○ Now included with MMR (MMRV) ● Passive immunization (immunocompromised) ○ Effective up to 3 days post-exposure ○ VZIG: varicella-zoster immunoglobulin (antibodies to the virus) ○ Used for immunocompromised exposed children and neonates born to mothers with varicella Shingles or Zoster ● Reactivation of the virus as it travels back down the nerve to the skin ● Beings as a local skin rash ● Characterized by confluent rash and pain ● Untreated rash lasts 2-5 weeks, infectious to those who have not had chickenpox ● Antivirals like acyclovir must be started within 48-72 hours of the rash ● Airborne infection - easily spread to susceptible individuals Complications ● PHN (Post Herpetic Neuraligia) ● 25-50% of patients >50 years ● Severe chronic pain for months or years ● Important to get treatment within 48-72 hours Smallpox (variola virus) ● Eradicated in the 1970s (first eradication of an infectious disease) ● Enveloped DNA virus ● Other members of the orthopoxvirus family are: ○ Vaccinia, Monkeypox, Cowpox... ● Vaccinia and Variola virus differ in only one antigen and cross react ● Immunity to smallpox = immunity to monkeypox ● Vaccinia used in smallpox vaccines (safe) ● Smallpox: two forms ○ Variola major ~30% mortality ○ Variola minor ~1% mortality ● Variola major presents in different ways: ○ Ordinary (discrete, semi-confluent, confluent) ○ Modified/mild ○ Flat and hemorrhagic (very severe) ● Infectious, but not nearly as infectious as flu ● Complications: lesions become infected secondarily with bacteria that may be on the skin, like Staphylococcus aureus; can lead to bacteremia and sepsis, even death Transmission ● ● ● Mucous membranes in upper respiratory tract Droplet transmission (coughs and sneezes) Also direct and indirect transmission: ○ Viral particles on objects (e.g. blankets) used for bioterrorism against Indigenous North Americans Treatment ● No good drug for treatment ● No effect for established disease Epidemiology ● NO ASYMPTOMATIC CARRIERS or SUBCLINICAL DISEASE (very mild disease) ● NO NON-HUMAN RESERVOIR (does not impact animals) Herpesviruses ● “herpes’ means to crawl or creep ● 8 viruses in group that are human pathogens ○ HSV-1 (cold sores) ■ Very common, > 90% infected, most in childhood ■ Transmitted by oral route or direct contact ■ Causes “cold sores” (daycares and elementary schools) ■ Remains latent in nerve endings (trigeminal nerve ganglia) and flares up with stress ■ Herpes gladitorium: wrestlers on body ■ Herpes whitlow: occupational hazard of healthcare workers ● HSV-2 (genital Herpes lesions) ○ Lesions - Herpes gladatorium ● HHV-3 (VZV) (chickenpox and shingles) ● HHV-4 (EBV) (infectious mononucleosis) ○ 85% of IM is caused by HHV4 ○ 15% of IM is caused by HHV5 ● HHV-5 (CMV) (congenital disease + disease in immunocompromised) ● HHV-6 (roseola) ● HHV-7 (sometimes roseola, otherwise?) ● HHV-8 (Kaposi’s Sarcoma-associated) ● Once infected, you have a viral genome in sensory ganglia for your lifetime Infectious Mono “Kissing Disease” ● Major cause: ○ EBV: Epstein Barr virus (HHV 4) DNA, Herpesviridae, enveloped, latent in B cells ○ Epstein-Barr virus causes all of the following EXCEPT ■ Bacillary angiomatosis, Infectious mononucleosis, Burkitt’s lymphoma, Nasopharyngeal carcinoma ● ● ● ● ● ● ● ● ■ >15 years is the age group wit the most severe symptoms ■ Causes infectious mononucleosis Infectious Mononucleosis (IM) (“kissing disease”) Most people have the infection when very young and have mild or sub-clinical infection More severe disease when older (teenagers, college students) Systemic effects on cardiovascular (heart) and lymphatic - enlarged spleen, dangerous because contact sports (spleen could rupture and you could die from it) systems Virus shed intermittently from saliva through life Symptoms ○ Fever, sore throat, swollen lymph glands in neck, general weakness, fatigue, enlarged spleen Production of heterophile antibodies (weird antibodies that agglutinate other mammals RBC) ○ No function known for these antibodies but they are used for lab tests (ex. Mono-spot test) ■ Heterophile antibodies are strange non clinically relevant antibodies that appear in infections with HHV-4 but not HHV-5; we use them for the test Ampicillin rash a complication (not just a rash!) if you have mono and are given beta-lactams; This is like a superantigen effect! ○ Give patients mono beta-lactam (ex. Penicillin, ampicillin), will get rash (can end up with extensive care ward) EBV related cancer ● Associated with Burkitt’s lymphoma and other B cell lymphomas ● Most common type of childhood cancer in Africa (lots of malaria in Africa, cause immune system to get depressed (EBV change B cells that grow and create tumors)) ● Association with malaria endemic areas (perhaps depressed immunity?) Fifth disease/parvovirus B19/erythema infectiosum/slapped cheek syndrome ● Parvovirus, DNA, nonenveloped ● Mild rash disease of childhood; usually no complications in children ● Pink lacy rash; cheeks become very red, which is usually the first noticeable sign in children ● Major complication: TAC (transient aplastic crisis) in pregnant women. Parvovirus has a tropism for nucleated red blood cells, and it invades and destroys these cells in the bone marrow. This means that the mother’s hemoglobin can drop 30%– 40% very quickly, and the fetus will not be getting oxygen. This leads to stillbirth/spontaneous abortion. RNA Virus Influenza virus ● Neuraminidase - these particles remain attach to the cell surface by sialic acid residues, allow viruses to leave host cell ● Hemagglutinin - viral release (cleavage reaction), responsible for attachment of the virus to host cells and binds to specific receptors on the surface of host cells, typically sialic acid residues on cell membranes; after binding HA mediates the fusion of the viral envelope with the host cell membrane, allowing the virus to enter host cell ● Retroviridae (HIV) ● Flaviviridae (Yellow fever virus, west nile virus) ● Orthomyxoviridae (Influenza A, B, C) ● Picornaviridae (Enterovirus) ● Coronavirus Measles (Rubeola) ● Maculopapular viral disease caused by rubeola virus, an enveloped paramyxovirus (RNA) ● Extremely infectious (airborne) ● 90% attack rate in susceptible households ● Systemic disease with rash ● Other closely related viruses are canine distemper and rinderpest ● One serotype, humans only natural host ● No latent or persistent infections ● Often complicated by secondary bacterial infections, like Staphylococcus aureus pneumonia and ear infections ● Blindness in children with Vitamin A deficiency ● Rare fatal complication: subacute sclerosing panencephalitis (SSPE several years later) Classic measles ● Rarely subclinical (can hardly notice it, most of the time have symptoms) ● Symptoms are respiratory: fever, malaise, anorexia, conjunctivitis, photophobia, myalgia ● Koplik’s spots (appear on buccal mucosa: red white and blue spots diagnostic of measles prior to rash) ● Maculopapular rash, starts behind ears, and spreads to face, upper arms and trunk, then legs ● Intense inflammation of lymphoid tissue and mucosa of the respiratory tract ● Tracheobronchitis and pneumonia common Measles causes immunosuppression ● Dendritic cells and monocytes are infected, antigen presenting activity compromised ● Circulating T lymphocytes are decreased by 50% ● Aberrant cytokine responses ○ IL-4 and IL-10 increased, skews Th1 (cell) - good for viral infections to Th2 (AB) - not as effective as Th1 ○ Reduced macrophage activation Vaccine ● Live attenuated measles vaccine 95% effective after one dose. ● For non-responders, a second booster will be effective in 95% (due to MHC II) of them ● For excellent herd immunity, want 95% vaccination coverage so you need to have everyone vaccinated in the population ● Attenuated measles virus first licensed in 1963 ● Combined measles, mumps, rubella and varicella vaccine (MMRV): ○ First dose at 12-15 mo ○ Second dose at 4-6 Rubella (German measles) ● RNA, Togaviridae, enveloped, one serotype ● Milder disease than measles ● Macular rash ● Complications: rare in children Adults: encephalitis Pregnant women: fetal development of congenital rubella syndrome (CRS) RSV (Respiratory Syncytial Virus) ● Enveloped, RNA, spread mainly by direct contact and occasionally droplet ● Most common lower respitratoy pathogen in infants ● Infants and children < 5 yrs (most commonly infected); elderly in nursing homes ○ Most common ause of serious LRTI in children <2 years of age ● Epidemics and seasonal: late winter and early spring ● Life-threatening pneumonia and bronchiolitis in infants ● Symptoms: coughing and wheezing ● Premature babies highest risk for serious disease ○ Due to prematurity - often have underdeveloped lungs ● Treatment – no effective antiviral, new mRNA vaccine ● Prophylaxis: Synagis monoclonal antibody, (passive immunization), given only to premature babies with other risk factors (very expensive! 15mg/kg,, $260 US $/kg monthly) Croup (children) (LRTI) ● Parainfluenza virus (PIV) (enveloped RNA) is a common cause of “croup”in small children ○ Swelling of mucous membranes in the respiratory tract ○ Larynx and trachea have non-expandable rings of cartilage and since children have narrow tubes, obstruction can occur ○ Typical seal-like barking cough Covid-19 (LRTI) ● New enveloped RNA virus belonging to the coronavirus family emerges in China late 2019, probably from a bat reservoir ● Able to establish infection in humans globally ● Four subtypes: alpha, beta, (human pathogens) gamma and theta (animal) ● ß : SARS-CoV, Mers-CoV (50-60% mortality rate) &“Covid-19 (Sars- CoV2)” ● Symptoms ○ Heterogeneous: symptoms may vary and include: ■ Fever, conjunctivitis, pharyngitis, coryza, headache, dizziness, generalized weakness, vomiting, diarrhea, dry cough, shortness of breath ■ Lack of taste and smell, fatigue ■ Severe disease usually presents after 9 days of infection How does this corona virus affect humans? ● ● Glycoprotein spikes: responsible for tropism and attachment to host cell Spikes have two functional units: S1 (used to bind to receptors on host cells) and S2 (used to fuse host cell and virus envelope) ● Main receptor for Covid-19: Angiotensin converting enzyme 2 (ACE2) ● ACE2 is highly expressed in lung, heart, ileum, kidney and bladder, on epithelial cells and some endothelial cells ○ ACE2 - angiotensin-converting enzyme 2 ○ Normally it breaks down proteins (especially angiotensin II) which can increase inflammation and the death of cells in the alveoli (critical for oxygenation of blood) ○ These harmful effects of ANG II are reduced by ACE2 ○ When COVID-19 is bound to ACE2 then it cannot prevent the damaging effects of ANG II - ACE2 receptors cannot function normally as an enzyme and break down excess angiotensin Pneumonia caused by SARS-CoV2 ● SARS-CoV2 can cause serious pneumonia especially in elderly and immunocompromised individuals ● Studies have shown that even in asymptomatic cases lungs are affected by the virus ● This corona virus attaches to ACE2 enzymes which are the receptors on cells and prevents the enzyme from breaking down angiotensin 2 which can be harmful to tissues. The inflammation caused by this virus results in a “cytokine” storm and serious consequences. ● Pandemic pressure enabled the development of anti-viral drugs that are somewhat effective at early stages as well good preventative vaccines. ● Mutates very quickly give rise to waves of infection ● Many studies are ongoing and indications are that 1/5 who are infected with this virus (even if they are asymptomatic) will suffer from Long-Covid Influenza A (LRTI) ● Influenza A,B,C are enveloped orthomyxoviridae, segmented RNA viruses ● Influenza A + B have 8 RNA segments, C has 7 ● Only Influenza A has subtypes ● A/Fujian/411/2002(H3N2) - M2 ion channel, M1 Matrix, neuraminidase, hemagglutinin, envelope ● Global epidemics - originated in pigs in Mexico ● The Spanish Flu of 1918 was caused by a H1N1 strain of Influenza A. We do not need the same death rate now due to many have either have had the infection and developed immunity, vaccination, and the virus has likely mutated to become less deadly ● We need a yearly vaccine due to antigenic drift - small mutations occurring that change the virus only slightly but it can change the effectiveness of the vaccine that you took last year. They make a new formulation of vaccine using fresh strains from the far east and Australia every year in an attempt to second guess the wave of virus; we do have some level of immunity against the virus from last year but this is not enough ● Oseltamivir is the drug that are used prophylactically Symptoms ● Malaise ● Fever ● Headache ● Myalgia (muscles aching) ● Cough ● Sore throat ● More severe in smokers (have damaged cells in respiratory tract) Incubation period and Infectious Dose ● Small infectious dose ● Incubation 1-5 days ● Virus viable on hard surfaces 24-48 hours ● Droplet transmission