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Exam 4

Person to person diseases:

 Airborne and droplets are the most contagious


 Streptococcal
o S. pyogenes – strep throat, beta hemolytic, impetigo, rheumatic fever, scarlet fever, strep
TSS, necrotizing
o S. pneumoniae – encapsulated is pathogenic, pneumonia (high mortality)
o Group A streptococci (pyogenes, GAS) virulence factors
 Lancefield (based on antigen)
 Surface M protein protects from phagocytosis
 Produces hyaluronidase-invasiveness, promotes cell-cell contact
 Produces streptokinase - dissolves clots and allows further invasion
 Streptolysin O (attacks sterols), streptolysin S (leucocidin)
 Erythrogenic toxin – superantigen
o Superantigens – produces inappropriately strong immune response
 Stimulate high number of T cells, bind to TCRs and MHCs in non-
specific manner
 Systemic reactions and shock
o Strep throat:
 Severe sore throat, rapid ELISA test, culture on BAP
o S. sequelae – incomplete or no antibiotic treatment
 Rheumatic fever
 M antigen similar to heart antigen  autoantibodies
 Scarlet fever – superantigens
o Erysipelas (St. Anthony’s Fire)
 Raised rubbery lesions, common before antibiotics, was high mortality
 Treat with antibiotics
o Impetigo – contagious skin infection – pyogenes or aureus
 Antibiotics
 Also Otitis media (ear infection) and mastitis
o Necrotizing fasciitis
 Deep layers of tissue, spread of toxin, surgical removal (antibiotics not fast enough)
o Strep treatments:
 Penicillin and derivatives
 Erythromycin
 Vaccine for S. pneumoniae for those at high risk
 Diptheria
o Exotoxin causes tissue destruction
 AB exotoxin
 Blocks protein synthesis
o Pseudomembrane formation
o Toxoid vaccination
o Treat with antibiotics and antitoxin
 Whooping cough (pertussis)
o Highly infectious, serious for infants
o Antibiotics not effective
o Vaccine (TDaP) – booster
 Booster during pregnancy spikes IgG antibodies which can cross placenta
 Meningitis
o Bacterial, viral, other
o Viral less severe
o Bacterial treated with antibiotics
o Caused by various (staph, strep)
o Meningococcal meningitis, meningococcemia
 Neisseria – airborne transmission
 Penicillin, chloramphenicol, cephalosporins
 Goes to bloodstream, causes rash then lesions  amputation
 Vaccine available (type A and B)
 Tuberculosis
o Mycobacterium
o Contagious – inhalation of bacteria into lungs
o Phagocytized, lives within macrophages  granulomas in lung
o Vaccine – bovine attenuated
o Antibiotic isoniazid (inhibits mycolic acid synthesis) and rifampin
 Hansen’s disease (leprosy)
o Mycobacterium - lives in macrophages
o Direct contact or respiratory transmission
o Incubation can be years, granulomas on skin
o Treat with antibiotics
o No vaccine
 Airborne: MMR
o Measles – deadly
o Mumps
o Rubella – teratogen
o Highly infectious, MMR vaccine (attenuated virus)
 Chickenpox – airborne
o Viral (varicella zoster)
o Herpes virus, latency in nerve cells can lead to shingles
o Contagious – droplets and fomites
o Systemic rash
o Vaccine (attenuated virus)
 Colds – rhinovirus, adeno, corona
 SARS – severe acute respiratory syndrome
o Coronavirus
o Spread by close contact, airborne
o Natural host was cat
o MERS – natural host camel
 Influenza
o Transmitted thru droplets
o Complications from secondary infections (pneumonia)
o RNA virus
o Influenza A, B, C (A most important to humans)
o Segmented genome  reassortment of DNA when more than one strain infects cell 
development of new strains
 Bird flu – bird and human stains infected pig, which then infected humans
o Influenza A:
 Antigenic drift – minor changes in surface proteins (point mutations)  epidemics
 Antigenic shift – reassortment of viral genes  new strains, major changes in H and
N  pandemics
o 1918 spanish flu – WW1, H1N1
o Cytokine storm – overreaction of healthy immune system  superantigen response
o Bird flu – H5N1, hantavirus, SARS also have cytokine storm
o Treatment: polyvalent vaccine (3 strains) – not perfect, shorten duration: amantadine,
rimantadine, flumadine inhibit viral replication; Tamiflu and Relenza prevent viral release
o Vaccine: shot is inactivated virus, spray is live weakened virus
o Swine flu – H1N1

Direct contact diseases:


 Staphylococcus
o Aureus – pyogenic, pneumonia, carditis, meningitis, TSS, scalded skin, food poisoning
o MRSA
o Staph produces coagulase – forms fibrins to wall off infection and protect it from
immune system, makes leucocidin
o S. Aureus virulence factors
 4 hemolysins (Beta helmolytic)
 Coagulase, fibrin clotting
 Leucocidin
 Superantigens (TSS toxin, exfoliating toxin A and B, enterotoxin A-E – food
poisoning)
o Scalded skin syndrome
 Exfoliating toxin blisters skin, young children
 Treat with IV antibiotics
o Sty – folliculitis at eyelid
o Furuncle (boil) – single hair follicle)
o Carbuncle – more than one follicle
o Treatment for skin infections varies from nothing, antibiotic ointment, heat, surgical
drainage
o MRSA
 Aureus that is methicillin resistant, infects open cuts
 Treat with vancomycin, phage therapy, maggot therapy
 Hepatitis
o Virus A-E
o Jaundice (too much bilirubin)
o Treatment – gamma globulins, antivirals, interferon alpha for hep C
o New treatment for hep C – combines 2 antivirals, named Harvoni
Hepatitis A Hepatitis B Hepatitis C
Type of virus RNA DNA RNA
Transmission Fecal-oral blood blood
Severity mild Can be severe Can be
severe
Carrier No Yes Yes
Chronic liver No Yes Yes
disease
Vaccine Yes Yes No
 Warts:
o HPV – genital (vaccine), dermal (warts)
 Mononucleosis
o Epstein Barr virus
o Replicates in B cells and epithelial cells of pharynx
o 50% of WBCs lymphocytes
o Monospot test – agglutination test for Ab
o Exhibits latency, usually has no symptoms but can be infectious
o Spread thru saliva, self limiting
o Burkitt’s lymphoma if immunocompromised
STDs (venereal diseases)
 Gonorrhea (the Clap)
o Neisseria
o Attach to epithelial cells of G-U tract and sperm
o Multiply in leukocytes
o May be asymptomatic, esp women (“Pill” favors growth)
o Drip of pus – men
o Can lead to pelvic inflammatory disease, sterility, transfer to infant, arthritis
o Easily develops resistance – 4 lines of drugs: sulfonamide, penicillin, quinolones,
cephalosporin + anti-chlamydial
o No vaccine
o Recovery does not confer immunity – many strains
 Non-gonococcal urethritis (Chlamydia)
o Often coincident with gonorrhea
o Often caused by Chlamydia
o Watery discharge
o Many asymptomatic, can lead to sterility, PID
o Reacts well to antibiotics, Zithromax, doxycycline
o Most prevalent bacterial STD
 Syphilis (The Pox)
o Bacterial spirochete (Treponema)
o Body fluids including saliva
o Does not survive refrigeration of blood
o Humans only reservoir
o Primary stage 4-6 weeks – chancres on genitals, lips – hard, painless lesion
 Primary latent phase
o Secondary stage – can last years – rash on palms and feet
 Secondary latent phase (sometimes ends here)
o Tertiary phase – permanent damage to cardiovascular and nervous system
 Gummas – inflammations (granulomas) – internal (NS), external (skin)
o Congenital syphilis
 Treponemes cross placenta, hutchinson’s teeth, perforated palate, saber shins,
saddle nose
o Treatment: not as resistant as gonorrhea – penicillin, tetracycline, erythromycin
o No vaccine, recovery does not confer immunity
 Chancroid (haemophilus)
o Painful bleeding lesions, common in tropical climates
 Ureaplasma urethritis, mycoplasmal urethritis
 Herpes
o HSV-1 cold sores – saliva, some genital
o HSV-2 genital herpes
o Latency
o Recurrent lesions
o Women – increases risk of miscarriage, C-section (passes to infant during birth), few
symptoms
o Neonatal herpes – skin vesicles or disseminated (neural, eye) – can die if disseminates
o Treatment: Acylovir, Ara-A, Vidarabin
 Antiviral agents for herpes group, lessons symptoms
 No vaccine, no cure for latency
 AIDS
o Recognized 1981
o Most due to HIV-1
o Must test positive for HIV and (1) CD4 T cell (T helper) count <200/mm3 or (2) CD4 T
cell count >200 and presence of opportunistic infections
o HIV endemic in US
o Fungal infections, pneumocystic pneumonia most common opportunistic disease,
parasitic infections (toxoplasma), TB, Viral or bacterial infections, Kaposi’s sarcoma
(young men in 80s)
 HIV
o Retrovirus – 2 identical ssRNA, carry reverse transcriptase – copies RNA into DNA
o Enveloped
o Attacks CD4+ cells – interaction between gp120 of virus and CCR5 co-receptor; after
attachment, fusion of envelope, insertion of nucleocapsid
 Uncoating of RNA, reverse transcriptase in cytoplasm  dsDNA to nucleus
(provirus – integrates into host genome)
o Diagnosis – ELISA screen for antibodies (not recent infections), HIV PCR detects viral
load (monitors treatment)
o Want low viral load and high CD4 count
o Treatment: HAART (highly active antiretroviral therapy) – at least 3 drugs at once, not a
cure, 6 categories (nucleoside RT inhibitors, non-nucleoside RT inhibitors, protease
inhibitor, fusion inhibitor, integrase inhibitor, entry inhibitor)
 AZT (azidothymidine) is nucleoside RT inhibitor
 Nucleoside analog, antimetabolites, drug resistance within weeks if
given alone
 Other NRTI: ddC, ddI, d4T, 3TC
 NNRTI – interaction with RT protein – block catalytic site, single mutation leads
to resistance – Nevirapine, efavirenz, delavirdine
 Protease inhibitors – peptide analogs, bind to HIV protease (required for viral
protein processing and virus maturation – cuts up polypeptide into proteins),
can see resistance
 Fusion inhibitors – binds to gp41 and inhibits fusion of envelope to CD4 host
cell, given when patients resistant to other drugs
 Integrase inhibitors – block integrase (integrates viral dsDNA into host genome)
 Entry inhibitors – CCR5 inhibitor on macrophage – required for initial viral
infection (Maraviroc/Selzentry blocks CCR5)
 HAART: 1 protease inhibitor or NNRTI + 2 NRTI
 Monitor viral load with RT-PCR, want non-detectable load (<500/ml)
 AIDS vaccine – many in trial, bone marrow transplant if donor CCR5 negative

Animal Transmitted Diseases: zoonoses


 Enzootic – endemic to certain animal populations
 Epizootic – epidemic proportions, increased potential for human infections
 Rabies
o Post-exposure prophylaxis
o Racoons, skunks, bats, foxes, coyotes (not possums)
o Rhabdovirus – large host range, travels to CNS
 Present in saliva  hydrophobia (fear of swallowing), incubation varies –
humans months, dogs 10-14 days
o Diagnosis – immunofluorescence of tissue postmortem (Negri bodies in brain), RT-PCR
o Treatment – rabies immune globulin (antibodies, passive)
Rabies vaccine – active (inactivated virus)
 Viral Hemorrhagic fevers: Hantavirus, Marburg, ebola
o Not normal human pathogens, don’t rely on humans for transmission, damage vascular
system, death by organ damage (not bleeding)
 Hantavirus:
o Hantavirus pulmonary syndrome (HPS) – respiratory and cardiac disease
o Hemorrhagic fever with renal syndrome (HFRs) – shock and kidney failure
o Transmission from rodents (aerosolization of droppings)
o Cytokine storm induced by superantigen?, drown in own fluids
o ELISAs for antibody presence or PCR for viral presence
o No cure or vaccine
 Marburg
o Infected monkeys, reservoir is bats
o Filamentous shaped virus – filovirus
 Ebola
o Filovirus
o Spread thru fluids, no cure/vaccine
o Bat reservoir?
o After death, patient still contagious – sweat – don’t touch them!
o Treat by supporting patient, keep hydrated

Arthropod Transmitted Diseases – bacterial


 Rickettsial diseases – typhus, spotted fever, ehrlichiosis
o Small intracellular bacteria, usually phagocytes, only grown in cells, mammalian hosts,
arthropod vectors (lice, fleas, ticks)
 Typhus:
o Rickettsia
o Vector – body lice
o Rash everywhere except face, palms, soles
o Treat with Tetracycline, chloramphenicol (antibiotics)
 Rocky mountain spotted fever
o Rickettsia
o Vector – tick
o Fever, headache, rash on whole body, untreated mortality 30%
o Treat with tetracycline, chloramphenicol (antibiotics)
 Ehrlichiosis
o Ehrlichia
o Humans, deer, rodents host
o Vector – tick
o Flu symptoms, decreased WBD, mild rash
o Treat with antibiotics
o HME (human monocytic ehrlichiosis)
o HGA (human granulocytic anaplasmosis)
o Caused by different ehrlichia strains
o Treat with doxycycline
 Lyme disease
o Spirochete
o Vector – tick (blacklegged tick)
 All life stages, even larvae, can carry it
 Prevent with Deet
o Humans and deer hosts, as well as rodents
o Headache, chills, fatigue
o Bullseye rash
o Chronic – arthritis, neuro
o Diagnose with ELISA, western blot, PCR
o Antibiotics treat, long term treatment (vaccine was withdrawn from market – poor
sales)
 Plague
o Yersinia
o Host – rodents, accidental humans
o Still occurs in SW USA – endemic to rodents
o Bubonic
 Flea bite
 Buboes – lymph nodes, gangrene
o Pneumonic
 Inhalation of bacteria
 Very contagious, high mortality
o Treat with antibiotics
 West Nile Fever
o Originally Egypt, endemic in US now
o Vector – mosquito
o Human, horse (40% mortality), bird hosts
o Usually mild in humans
o No treatment, only prevention
o Complications more likely in aged pop (encephalitis, meningitis)
o ELISA test
o Horse vaccine, no human vaccine
 Yellow Fever
o Vector – mosquito
o Monkeys likely reservoir
o Self-limiting, either survive or not – high mortality
o Central and south America, Africa
o US research as bio weapon
o Vaccine available
o No treatment
 Viral encephalitis
o Inflammation of brain
o Mosquito vector
o Eastern and western equine, Venezuelan, saint louis – caused by different viruses
o Eastern equine most deadly
o Bird as intermediate carrier
o No treatments or vaccines
 Dengue fever
o Bone and joint pain, flavivirus
o Self-limiting
o Usually survive 1st infection, have immunity to that strain - 2nd infection from diff.
immunological strain causes hemorrhagic disease
o Mosquito vector
o No treatment, no vaccine
 Chikungunya
o Mosquito vector
o Africa, asia, Europe
o Fever, hand/feet joint pain, rash, muscle pain, most feel better within a week
 Zika
o Most are asymptomatic or mild
o During pregnancy causes microcephaly and brain defects
o Mosquito bites, sex, spread from woman to fetus

Arthropod transmitted diseases: protozoa


 Protozoa – single cell euk
 Malaria
o Plasmodium (vivax most common, falciparum most deadly)
o Complex life cycle
o Mosquito vector, both mosquito and human are hosts (part of life cycle carried out in
both)
 Development of sporozoites in mosquito, development of merozoites in humans
 Infect human RBC
 Some stages release by RBC are gametocytes that are taken up in mosquito
blood meal  gametes  salivary gland for new cycle
o Diagnosis: presence of plasmodium in blood, immunoassay, PCR
o Quinine first effective drug (gin and tonics)
o Primaquine, artemisinin
o No vaccine, multiple drug resistance occurring
o With sickle cell anemia, parasite cannot develop with abnormal hemoglobin
(heterozygotes are malaria resistant)
o Africans have MHC combination that resists as well
o Prevent with insecticides (DDT), bed nets, prophylactic drugs when traveling
 Leishmaniasis
o Sand fly vector
o Initial infection cutaneous (lesions), leads to systemic fatal infection (visceral disease)
o Drug resistance
 African sleeping sickness
o Trypanosome
o Tsetse fly
o Sub-Saharan Africa
o Drugs are toxic and resistance develops
 Chagas disease
o Trypanosome
o Kissing bug vector
o South America, mild initial disease, but later chronic disease fatal  heart problems
o Drugs most effective in initial infection
o Cure is heart transplant
o Autoimmune disease?
 Helminths Lymphatic filariasis (elephantiasis)
o Legs swollen with lymph
o Parasitic worms
o Larvae enter by bite of mosquito, mature in blood  lymph nodes, blocks drainage,
cannot be reversed
o Mectizan drugs
o Haiti program puts DEC in salt
 Loaisis
o Loa loa worm transmitted by deer flies
o Africa
o Adult worms live in eyes or under skin, does not cause blindness
 River blindness
o Roundworm – microfilaria, transmitted by blackflies
o Invade eyes and blood vessels, become fibrous
o Treatments (mectizan) helps prevent if caught before blindness

Fungal Infections
 Yeast (single cell), molds – pathogens of plants, only ~50 species cause human disease
 Mycotoxins
 Mycoses – infections in/on body, problem for immunocompromised
 Candidiasis
o Thrush, vaginitis, nails
 Madura food
o Soil organisms
 Athletes foot, fungal infection of the eye, ringworm
o Antifungal treatments treat most (eye is harder to treat)
 Treatment – treatments topical to limit toxicity (eukaryotes), unique sterol-ergosterol-azoles
target, some drugs target fungal cell wall and chitin
Bacterial soil borne
 Tetanus – clostridium
o Soil contaminated puncture wound
o Potent exotoxin
o Organism is non-invasive
o Blocks relaxation of muscles
o Treat with antitoxin and antibiotics, prevent with vaccine (needs booster)
Water:
 Most common source of infection
 Coliforms – bacteria found in fecal matter
o Most are enteric bacteria (E.coli, Klebsiella, Enterobacter)
o Coliform test – water thru filter, filter on EMB plate, should be negative (<1/100ml) for
drinking water
 EMB is selective and differential
 Effluent – what is released after sewage treatment
 Treatment:
o Primary: physical removal
o Secondary: biological removal
 Activated sludge floc (Zooglea ramigera)
o Tertiary: chemical and physical
 UV light, chlorine
 Septic tanks:
o Microbes decompose sludge, has to be pumped out, gravel and soil do final filtration
into groundwater
 Purification:
o Deep wells don’t need purification
o Flocculation – precipitation of insoluble by adding alum, chlorination
o Potable and recreational water sources of infections
 Traveler’s diarrhea
o Various strains of E. coli – 3-4 days
 Cholera
o Asia, south America, Africa
o Vibrio
o Fecal contamination of water
o Shredding of intestinal lining due to enterotoxin, rice water stools
o Replace fluids and electrolytes, antibiotics don’t do much
o Vaccines available but short term
 Legionnaire’s disease
o Water distribution systems, cooling towers, aerosols, not person to person
o Mild symptoms (Pontiac fever), self-limiting
o Older pop – pneumonia
o Treatment – antibiotics
 Typhoid fever:
o Salmonella
o Bacteria multiply in macrophages, invade intestinal mucosa
o ~4 weeks of symptoms
o Treated with antibiotics (vaccine available)
o Some are carriers (Typhoid Mary)
 Giardiasis (a protozoa)
o Fecal-oral transmission of cysts
o Filtration eliminates, but not chlorine or UV alone
o Filtration + boiling best
o Cysts attach to intestinal wall, diarrhea, people can be carriers
o Drugs available (Eukaryote)
o Diplomonad
 Cryptosporidiosis (protozoa)
o Cysts resistant to chlorine and UV – more resistant than Giardia
o 50% of waterborne outbreaks
o Self limiting, mild diarrhea (2 wks)
o Immunocompromised more serious
 Amoebiasis
o Amoebic dysentery
 Protozoa
o Fecal-oral (cysts)
o 30+ bowel movements per day
o Drugs available, but not great
 Protozoan Meningoencephalitis
o Brain-eating, lives in soil, contaminates water
o Enters nose and burrows into brain  death within a week
o Outbreaks in summer – shallow warm water
o Neti pot warning
 Blood fluke life cycle (Schistosoma)
o Fluke is a flatworm
o Fecal-oral
o Eggs hatch in water  free-swimming form, enters snail  burrows into human
o Bloody urine
o Responds to Mectizan
 Guinea worm
o Humans drink water contaminated with juvenile worm or crustacean that has juvenile
worms
o Worms develop and nest under skin – grow long, when step into water, worms come
out
o Can’t be treated with mectizan
o Need to pull it out slowly over a month
o Carter center trying to eradicate it
Food – borne:
 Food preservation – cold, pickling, drying, heating, chemical, irradiation
 Foodborne illnesses follow normal patterns, exponential phase depends on temp and nutrients
 Food poisoning: intoxication, presence of toxin (true food poisoning is when food itself is the
cause)
 Vs food infection – organism lives and grows and causes illness
 Microbial sampling – rapid tests to find pathogens in food
 Staphylococcus intoxication
o Not usually reported
o Superantigenic enterotoxin, heat stable
o Antibiotics not helpful
o Custard, creams
o Refrigeration good inhibitor
o S.aureus – rapid onset (30min), vomiting, diarrhea, 24 hours
 Clostridium
o C. perfringes
 Most common food poisoning
 Diarrhea, cramps, no vomiting, 24 hours
 Meat, fish – 7-15 hrs after ingestion
o C. botulinum
 25% fatal
 Neurotoxin
 Foods not cooked after processing – canned corn, honey
 Muscle paralysis, die by suffocation
 Treat with antitoxin (antibodies produced in horses)
 Infections:
 Salmonellosis
o Colonization of Salmonella
o Fecal/oral, uncooked eggs, poultry
o 8-48 hrs after ingestion
o Vomiting, fever, diarrhea
o Self limiting 48 hrs – 1 week
o Antibiotics if septicemia
 Campylobacter
o Sporadic cases
o Common, bloody diarrhea (2-5 days)
o Common in birds, poultry
 E. Coli
o Most non-pathogenic
o O-LPS, H-flagellar antigens
o Enterotoxin (verotoxin/shiga toxin)
o Bloody diarrhea, kidney failure
o O157:H7 infection
 Cook hamburger thoroughly
 Vegetables and ground beef
 3-4 days after ingestion
 Bloody diarrhea, fatal in very young or elderly
 Treatment: replace fluids, maybe antibiotics
 Listeria
o Psychrotolerant
o Elderly and pregnant most susceptible
o Treat with IV antibiotics
 Shigellosis (bacillary dysentery)
o Dysentery = severe diarrhea with cramping
o Shigella (4 species)
o 3 days after ingestion
o Tenesmus (rectal cramping)
o Fecal/oral or through food and water
o Outbreaks in crowded living conditions
o Treatment: replace fluids, antibiotics
 Norovirus and rotavirus
o Vomiting, 24 hours
 Toxoplasmosis
o Protozoa
o Cat feces and undercooked meat
o Self-limiting
o Pregnant women: blindness, stillborn, mental retardation
 Tapeworm
o Infects cattle , from feces
o Worm makes cyst in cow muscle, goes to intestines
o Eggs travel and encyst (serious if in brain or eye)
o Mectizan treats
 Roundworm/trichinosis
o Similar to tapeworm, but pigs instead of cows
o Symptoms like food poisoning
o Muscle pain
o Freezing meat kills cysts

Industrial Micro:
 Biofuels
 Bioconversions/biotransformation:
o Use microbes to simplify or reduce cost of chemical synthesis
 Bioremediation
o Microbes to transform harmful substance into non-toxic ones
 Food
o Yeast, algae, bacteria
o Baker’s yeast
o Cultured buttermilk, sour cream, yogurt, fermented milk beverages
o Cheese – curd is solid, whey is liquid waste, salt added, ripening – action of
microorganisms on curd
o Vinegar (alcohol  acetic acid), requires bacteria
o Sauerkraut, pickles, olives, Poi all require bacteria
o Soy sauce (mold – fungus)
o Beer, wine, spirits – brewer’s yeast
 Genetic engineering
o Restriction enzymes from bacteria
o Recombinant DNA, transgenic, cloning
o Microbial production of animal proteins (somatotropin/growth hormone)
o GMO/transgenic organism – permanent presence of foreign genes
 Improve productivity or disease resistance, herbicide resistance
 Insect resistance
o Gene therapy – hereditary diseases, replacement gene therapy
 Technical difficulties (vectors – retrovirus?)
 CRISPR/CAS9 – archaea and bacteria evolved system to repair DNA, can
remove/introduce mutation

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