Current Diseases

1
Current Diseases

• Staphylococcus
• Clostridia
• Food-borne bacteria
• Malaria
• Influenza
• Common cold
• HIV
• HPV

2
Staphylococcus G coccus

• S. aureus and S. epidermidis (and 21 others).
• S. aureus much worse, S. epi an opportunist.
• Sturdy, salt tolerant, fac anaerobes clusters
• S. epidermidis common on skin, S. aureus less.
• Diseases of S. aureus
• Invasive skin diseases (rashes, abscesses)
• systemic diseases (bacteremia, organ and bone
  infections)
• Toxin toxic shock syndrome, scalded skin
  syndrome, food poisoning
• Diseases spread by fomites and direct contact.

3
Characteristics of S. aureus infections
tray.dermatology.uiowa.edu/ DIB/SSSS-002.htm
www.omv.lu.se/.../ rorelse/popup/01d1x.htm
4
S. aureus virulence factors Rx

• Capsules, hyaluronidase, staphylokinase,
  beta-lactamases (destroy penicillins),
  leukocidins
• Toxins various, including TSS toxin, exfoliatin,
  and enterotoxins (heat stable)
• 95 resistant to penicillin, but now many
  resistant to methicillin, oxacillin. Treatment
  usually clindamycin (oral) or vancomycin (IV).
• S.aureus carried by 30-40
• Well adapted to life with humans
• http//www.textbookofbacteriology.net/staph.html

5
Clostridium G rods

• Strict anaerobes! Endospore formers. Toxigenic
• Common in soil, sewage animal GI tracts
• Produce neurotoxins, enterotoxins, histolytic
  toxins
• Four important species C. perfringens, C.
  botulinum, C. tetani, and C. difficile.
• C. perfringens
• Food poisoning cramps and diarrhea
• From injury myonecrosis to gas gangrene
• Fermentation in tissues, killing of tissues and
  spread of cells into anaerobic areas.
• Oxygen treatment, debridement, amputation

6
More clostridia

• C. difficile normal GI microbiota
• Cause of pseudomembranous colitis, resulting from
  overgrowth following broad spectrum antibiotics
• Damage to GI wall can lead to serious illness
• Nosocomial infection, easily transmitted
• C.botulinum cause of botulism
• Usually acquired by ingestion intoxication
• Food borne, infant (no honey), wound
• Produces neurotoxin, inhibits acetylcholine
  release
• Flaccid paralysis Botox deadly poison / beauty
• Mouse bioassay administer antitoxin

7
Opposing muscle groups
When biceps contracts, triceps relaxes. When
triceps contracts, biceps relaxes. Excitatory
neurons send signal to contract, inhibitory
neurons send signal to NOT contract.
http//upload.wikimedia.org/wikipedia/sv/thumb/d/d
d/185px-Muscles_biceps_triceps.jpg
8
Function of nerves
http//upload.wikimedia.org/wikipedia/fr/thumb/e/e
4/200px-Synapse.png
http//www.people.virginia.edu/dp5m/phys_304/figu
res/motor_unit.jpg
9
More clostridia-2

• C. tetani cause of tetanus
• Growth in anaerobic wounds, makes tetanus toxin
• Toxin prevents action of inhibitory neurons
• Opposing muscle pairs both contract
• Spastic paralysis, leading to death.
• Recommendation is booster shot every 10 years
• Toxoid vaccine, with diphtheria toxoid
• No natural immunity you would die first.

10
Gram negative rods

• Enteric bacteria
• Gram negative, rod shaped, facultative anaerobes,
  non-spore forming, oxidase negative
  Proteobacteria
• Possess endotoxin
• Medically significant but taxonomically similar
• Distinguished with biochemical tests and
  serological tests.
• Serological tests using specific antibodies (as
  found in serum) to distinguish small differences
  in surface molecules of bacteria.

11
http//www.ratsteachmicro.com/Assets/Enterobacteri
aceae/Enterobact_diagram2.gif
12
E. coli friend or foe?

• E. coli cause of 90 of urinary tract infections
• Most strains common to GI tract, not harmful
  there.
• Strains have fimbriae needed for attachment
• Proanthocyanidins in cranberry juice interfere
• E. coli common cause of diarrhea
• Many strains possess genes (some on plasmids)
  that code for additional virulence factors like
  exotoxins which cause disease
• E. coli O157H7 possesses shiga toxin strain
  causes hemolytic uremia syndrome, damages
  kidneys.
• E coli strains classified as EHEC, EIEC, EPEC,
  etc.
• Enterohemorrhagic, enteroinvasive, etc.

13
Truly pathogenic enterics

• Salmonella species so closely related that they
  are really all S. enterica. But medically,
  species epithets still used S. typhi and others.
  Divided serologically.
• Present in eggs, poultry, on animals such as
  reptiles
• Large dose results in food poisoning diarrhea,
  fever, etc.
• Cells phagocytized by intestinal lining cells,
  kill cells causing symptoms, may pass through
  into blood.
• S. typhi typhoid fever. Spread through body
• Gall bladder as reservoir Typhoid Mary
• http//www.pbs.org/wgbh/nova/typhoid/
• Importance of clean water and sewage treatment.

14
Truly pathogenic enterics-2

• Shigella especially S. sonnei (most common) and
  S. dysenteriae (most serious) cause shigellosis.
• Food, flies, fingers, feces, fomites very small
  infectious dose, personal hygiene important in
  prevention.
• Infection of intestinal lining damaged, cells
  pass directly from cell to cell cramps,
  diarrhea, bloody stools.
• S. dysenteriae produces shiga toxin which
  inhibits protein synthesis, increases damage.
• Most serious problem with diarrheal diseases in
  general is dehydration.

15
Gram negative curved rods

• Vibrio comma shaped
• Like enteric but oxidase positive polar flagella
• Halotolerant to halophilic, grow in estuarine and
  marine environments
• V. cholerae cause of cholera
• Toxin-mediated severe diarrhea
• Salt, fluid leave intestinal cells, patient dies
  of dehydration.
• Oral rehydration therapy (ORT) water, salts, and
  glucose, now saving lives.
• Causes pandemics that spread around the world
• Lack of adequate sewage treatment

16
Campylobacter

• Campylobacter jejuni number one cause of
  bacterial gastroenteritis zoonotic
• More common than Salmonella and Shigella combined
  for food borne disease.
• Most retail chickens are contaminated improperly
  cooked chicken and contaminated milk typical
  vehicles.
• Low infectious dose

http//www.shef.ac.uk/staff/newsletter/vol23no10/i
mages/campylobacter.gif
17
Helicobacter pylori

• Cause of ulcers and gastritis
• 2005 Nobel Prize for Medicine or physiology to
  Barry Marshall and J Robin Warren
• Unusual because it can live in stomach
• Produces urease enzyme
• Released ammonia neutralizes stomach acid,
  irritates stomach lining.
• Basis for radioactive urease test.
• Correlated with stomach cancer.

http//s99.middlebury.edu/BI330A/STUDENTS/KASSIS/i
mages/pylori1b.jpg
18
Rogues gallery-4

• Sporozoans
• Plasmodium the cause of malaria, several
  species
• Involves mosquito, liver, red blood cells in a
  complex life cycle.
• Features a synchronous bursting of RBCs with
  fever, delerium, followed by rest and recovery,
  then cycle
• Number one cause of global mortality and morbidity

Yearly 300-500 million new cases 1 million
deaths.
Intracellular plasmodia
www.sirinet.net/ jgjohnso/plasmodium.html
19
Life cycle of Plasmodium
www.sirinet.net/ jgjohnso/plasmodium.html
20
In the poorest parts of the world, where
effective window screens are lacking,
insecticide-treated bed nets are arguably the
most cost-effective way to prevent malaria
transmission. One bed net costs just 10 to buy
and deliver to individuals in need. One bed net
can safely last a family for about four years,
thanks to a long-lasting insecticide woven into
the net fabric.
21
Orthomyxovirus

• Influenza a serious respiratory disease
• Virus has a segmented genome
• 8 different RNA molecules
• Spikes Hemagglutinin and Neuraminidase
• Major antigens recognized by immune system
• Antigenic drift and shift
• Drift small mutations, making host susceptible
• Requires new vaccine each year
• Shift major mixing of RNAs, whole new virus.

22
View of flu
http//www.astrosurf.org/lombry/Bio/virus-influenz
a.jpg http//www-micro.msb.le.ac.uk/3035/3035pic
s/flusection.jpg
23
Nature of influenza

• Attack on respiratory tract
• Kills ciliated epithelial cells, allows bacterial
  infections.
• Release of interferon from cells causes symptoms
• H antigen (hemagglutinin) for attachment
• That it agglutinates RBCs is an artifact
• N antigen neuraminidase
• Cuts of the sugar on the glycoprotein receptor
• Allows new virions to escape from cell without
  getting stuck

24
Role of H and N spikes and host cell
polysaccharide
25
influenza

• Changes in H and N (antigenic shift)
• Mixing of viruses that infect birds, pigs,
  produce new strains able to jump to humans.
• New antigenic type leaves population unprotected
• Numerous epidemics throughout history
• Flu of 1918-1919 killed 20 million
• Asia watched very carefully bird flu?
• Flu vaccines made from deactivated viruses
• Slow process (vaccine made in eggs), so every
  year correct strains are guessed.
• Cell culture would be quicker but more

26
The Common cold

• Rhinoviruses have many serotypes
• Variants, caused by easy mutation of RNA
• Immune system cant recognize all differences,
  but some protection with age.
• Multiplies in narrow temperature range,
  nose/sinus cooler than body temperature
• Other cold viruses
• Coronavirus (best known cousin causes SARS)
• Adenovirus (DNA virus), some serotypes cause GI
  infections

27
HIV Human Immunodeficiency Virus

• Host range
• Main types of cells infected T helper cells and
  dendritic cells (including macrophages,
  microglia)
• Have CD4 and CCR5 glycoproteins on surface
• Infection process
• RNA is copied into cDNA by reverse transcriptase
• cDNA inserts into host chromosome
• New RNA made
• Protein precursor made, then processed assembly
  occurs
• Virions bud through cell membrane

28
Disease process

• Chronic infection
• T cells continually made, continually destroyed
• Eventually, host loses
• AIDS diagnosis
• Acquired Immuno Deficiency Syndrome
• CD4 cell count below 200/µl
• opportunistic infections
• Examples of opportunistic infections
• Pneumocystis carinii pneumonia (PCP pneumonia)
• Kaposis sarcoma Tuberculosis several others

29
Prevention and Treatment

• Prevention is easy
• Practice monogamous sex, avoid shared needles
• HIV cannot be spread by casual contact, skeeters
• Drug treatment
• Nucleoside analogs such as AZT
• Protease inhibitors prevent processing of viral
  proteins

Nifty animation at http//highered.mcgraw-hill.co
m/sites/0072495855/student_view0/chapter24/animati
on__hiv_replication.html
30
HPV

• Papilloma virus
• Cause of warts, in this case, genital warts
• Virus tricks cell into preparing for cell
  division
• Protein E7 binds to pRB
• Leads to greater susceptibility to cancer,
  particularly cervical cancer (and penile and anal
  cancer)
• Especially those viral strains that arent good
  at causing actual warts
• CDC researchers estimated 20 million people in
  the US have human papillomavirus type16 (HPV-16)
  infections (50 of all cervical cancers)

31
Gardasil

• New vaccine
• Protects against HPV types 16, 18, 6, and 11
• These biotypes account for 70 of cases of
  cervical cancer and 90 of cases of genital
  warts.
• Vaccine a recombinant vaccine w/ capsid proteins
• Estimate 3,700 to die of cervical cancer in 2006
• Controversy should it be mandatory?
• Religious right, big Pharmaceutical lobby, etc.