Infectious disease 6

Mortality rates of tetanus in infants is
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Mortality rates of tetanus in infants is
90%
Historically, Clostridium spp. (ex. C. perfringens) were a leading cause of
wound infections in soldiers—this has declined with advancements in prompt, adequate medical treatments (prophylaxis and antisepsis)
Likewise botulism (C. botulinum) and tetanus (C. tetani) have declined in developed nations to hundreds of cases per year in U.S. (CDC)—because of
public awareness and widespread immunization are credited
Globally there are approx. 1,000,000 cases/year for each
clostridium species
Clostridium can be both
obligate or opportunistic pathogens
routes of entry for closteridium include both
ingress (ingestion) and parenteral (wounds) mechanisms
Most Clostridium spp. are characterized by
acute, toxin-associated infections and are non-invasive
C. tetani enters its host
parenterally through breaks in the skin (ex. puncture) then it replicates and produces tetanospasmin
C. tetani death is due to
cardiac/pulmonary failure
Tetanospasmin is a
neurotoxin - TENT
Tetanospasmin toxin type isan AB toxinbotulinum toxin (which is possibly the most lethal in the world) and2.5 lbs of botulinum toxin would be enough to kill everyone on earthAB type toxin have some target in the cell that they bind to andmodify the way the cell actsTetanospasmin interfereswith GABAGABA is an inhibitory neurotransmitter thatblocks acetylcholine release at synaptic junction by using an inhibitory axon.GABA general function at the muscular synapse is to inducemuscle relaxation and stops muscle contractionTetanospasmin inhibits release of GABA from inhibitory axon by blocking GABA containing vesicles leading touncontrolled release of acetylcholine resulting in tetanus (spasms, muscle rigidity, convulsion and death)Botulinum toxin it blocks delivery ofacetyl choline leading to muscle relaxation and ultimately paralysisDiseases like cholera ride the coat tails of war and famine is said because when people are displaced cholera becomes endemic to certain regions because it's becomestransmitted fecal-orally through contaminated food or waterCholera is an epidemic and life-threatening diarrhea characterized byacute diarrheagenic illness, often accompanied by vomiting, and resulting in hypovolemic shock and acidosisCholera is caused by certain members of the speciesVibrio cholerae, which can also cause mild or subclinical infectionsCholera is transmitted by thefecal-oral routeV. cholerae colonize the small bowel, where they secrete thepotent cholera enterotoxin, CT (aka choleragen)Cholera toxin CT is an ADP-ribosylating toxin that modulatescAMP productionCT is a prototypicAB5 toxin :The CT A domain (27 KDa) consists of2 subdomains (A1 and A2),CT B domain is ahomopentameric B domain (57 KDa) and the B domain binds up to 5 molecules of ganglioside receptors (GM1) on intestinal epithelial cellsCT endocytosis is followed by aGM1-dependent trafficking to the host endoplasmic reticulum and subsequent release of A1 catalytic peptide into the cytosol from ERUncontrolled secretion of Cl- from CT toxin action into the gut lumen results inosmotic imbalance, & massive water loss from mucosa and vasculature leading to severe diarrhea