Food

 Poisoning  
-­‐ more  than  200  known  diseases  are  transmitted  through  food.  The  causes  of  foodborne  
illnesses  include  viruses,  bacteria,  parasites,  toxins,  metals  and  prions,  and  symptoms  
range  from  mild  gastroenteritis  to  life-­‐threatening  neurologic,  hepatic  and  renal  
syndromes  
 
 
 
Major  Infectious  Causes  of  Acute  Diarrhea  
1. bacterial:  Aeromonas  spp,  Campylobacter  spp,  Clostridium  difficile,  E.  coli(entero,  
hemorrhagic,  invasive,  pathogenic,  toxigenic),  Salmonella  enteritidis,  Shigella  spp,  
Yersinia  enterocolitica  
2. viral:  Adenovirus,  Astrovirus,  Calicivirus,  Norwalk(noroviruses),  Rotavirus  
3. parasitic/protozoan:  Balantidium  coli,  Cryptosporidia,  Cyclospora  cayetanesis,  
Entamoeba  histolytica,  Giardia  lamblia,  Isospora  helli,  Microsporidia  
4. food  poisoning:  -­‐  Bacillus  cereus,  Clostridium  perfringes,  E.  coli,  Listeria  
                                                                     monocytogenes,  S.  aureus  
                                                                 -­‐  Vibrio  parahemolyticus,  Salmonella  spp,  Yersinia  enterocolitica  
 
 
Food  poisoning  falls  into  3  categories:  
-­‐ infectious/parasitic  infestations  acquired  by  eating  food  contaminated  with  infectious  
microorganisms/parasites  
-­‐ clinical  problems  that  result  from  eating  food  contaminated  with  toxins  
-­‐ clinical  sequelae  from  eating  inherently  poisonous  animals,  plants,  or  mushrooms  
*some  overlap  occurs  between  these  different  categories*  
 
 
 
Mechanism  of  Acquiring  Bacterial  Virulence  Genes  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
All  microbes  causing  food  poisoning  have  general  property:  they  are  capable  of  producing  
enterotoxins  of  various  types.  Despite  of  difference  in  mechanisms  of  their  action,  all  of  them  
result  in  one  –  increased  secretion  of  liquid  in  lumen  of  intestine.  As  a  rule,  these  toxins  
begin  to  develop  microbes  on  foods,  before  ingestive  microbes.  To  it  is  explained  extremely  
short  incubation  period  at  food  poisoning.  
Brief  Description  of  Exotoxin  
-­‐ Exotoxins,  unlike  endotoxins,  are  protein  toxins  released  from  viable  bacteria.  They  form  
a  class  of  poisons  that  is  among  the  most  potent,  per  unit  weight,  of  all  toxic  substances.  
Exotoxins  are  produced  by  some  members  of  both  gram  positive  and  gram  negative  
genera.  The  functions  of  these  exotoxins  for  the  bacteria  are  usually  unknown,  and  genes  
for  most  can  be  deleted  with  no  noticeable  effect  on  bacterial  growth.  In  contrast  to  the  
extensive  systemic  and  immune  system  effects  of  endotoxin  on  the  host,  the  site  of  action  
of  most  exotoxins  is  more  localized  and  is  confined  to  particular  cell  types  or  cell  
receptors.  
-­‐ Exotoxins  can  be  grouped  into  several  categories(eg:  neurotoxins,  cytotoxins  and  
enterotoxins)  based  on  their  biologic  effect  on  host  cells.  Enterotoxins  stimulate  
hypersecretion  of  water  and  electrolytes  from  intestinal  epithelium  and  this  produce  
watery  diarrhea  
 
 
 
 
Rabbit  ileal  loop  assay  is  used  to  investigate  whether  or  not  a  person  has  been  infected  
with  enterotoxin  of  E.  coli(if  infected,  massive  secretion  of  fluid  into  ligated  intestinal  
loops  is  showed)  
 
 
 
 
Pathogenesis  of  Food  Poisoning  
-­‐ pathogenesis  begins  with  ingestion  of  organisms  and  its  toxins  contaminated  in  food,  
which  then  faces  normal  gastric  acid  barrier.  Bacteria  appear  to  be  sensitive  to  gastric  
acid,  neutralization  by  gastric  acid  decreases  infection  dose  by  100  to  1000  folds  
-­‐ as  the  microbes  causing  food  poisoning  have  no  invasive  properties,  the  inflammatory  
reaction  in  the  intestine  is  expressed  weakly.  All  clinical  picture  is  caused  by  action  of  
enterotoxins.  It  explains  also  short  duration  of  current  of  disease.  The  colon  is  
not(rarely)  involved  in  inflammatory  reaction  
-­‐ the  prototypical  enterotoxin  is  cholera  toxin,  a  protein  comprised  of  one  A  and  5  B  
subunits.  The  A  subunit  contains  enzymatic  activity  of  toxin,  while  B  subunit  pentamer  
binds  holotoxin  to  the  enterocyte  surface  receptor,  the  ganglioside  GM1.  After  the  
binding  of  holotoxin,  a  fragment  of  the  A  subunit  is  translocated  across  the  eukaryotic  
cell  membrane  into  the  cytoplasm,  where  it  catalyzes  and  causes  persistent  activation  of  
adenylate  cyclase.  The  end  result  is  an  increase  of  cAMP  in  the  intestinal  mucosa,  which  
increases  Cl-­‐  secretion  and  decreased  Na+  absorption,  leading  to  loss  of  fluid  and  
production  of  diarrhea  
-­‐ the  consequently  increased  Cl-­‐  secretion  and  decreased  Na+  absorption  combine  to  cause  
net  isotonic  electrolyte  loss  that  must  be  replaces  to  prevent  severe  dehydration  and  
hypotension  and  its  potential  consequences  
-­‐ other  strains  produce  the  heat-­‐stable  toxin(STa)  and  other  types  of  enterotoxins  
 
 
 
 
 
 
 
 
 
 
Food  Poisoining  by  Staphylococcus  
-­‐ S.  aureus  cause  disease  by  invasion  and  elaboration  of  exotoxins.  S.  aureus  produces  a  
wide  variety  of  exoproteins  that  contribute  to  its  ability  to  colonize  and  cause  disease  in  
mammalian  hosts.  Nearly  all  strains  secrete  a  group  of  enzymes  and  cytotoxins  which  
includes  4  hemolysins(α,  β,  γ,  δ),  nucleases,  proteases,  lipases,  hyaluronidases  and  cell  
agenase.  The  main  function  of  these  proteins  may  be  to  convert  local  host  tissues  into  
nutrients  required  for  bacterial  growth.  Some  strains  produce  one/more  additional  
exoproteins,  which  include  enterotoxins(SEA,  SEB,  SECn,  SED,  SEE,  SEG,  SHE,  SEI),  other  
toxins(toxic  shock  syndrome  toxin-­‐1(TSST-­‐1),  exfoliative  toxins(A  and  B),  and  
leukocidin).  Each  of  these  toxins  is  known  to  have  potent  effects  on  cells  of  the  immune  
system,  but  many  of  them  have  other  biological  effects  as  well  
-­‐ All  enterotoxins  thus  far  identified  share  a  number  of  important  properties,  including:  
-­‐  an  ability  to  cause  emesis  and  gastroenteritis  in  humans  
-­‐  superantigenicity*  
-­‐  intermediate  resistance  to  heat  and  pepsin  digestion  
*The  name  “superantigens”  is  based  on  the  unusual  non-­‐antigen-­‐specific  activation  of  T-­‐cells  
 
 
 
Epidemiology  
-­‐ humans  serve  as  a  rich  reservoir  for  S.  aureus  to  produce  exoproteins  and  may  play  a  role  
in  the  etiology  of  gastrointestinal  diseases  caused  by  this  organism  
-­‐ most  cases  of  Staphylococcal  food  poisoning  are  caused  by  contamination  from  infected  
human  carriers.  Food  is  contaminated  by  S.  aureus  when  food  is  prepared  by  non-­‐
hygienic  individuals  who  are  carriers  of  this  organism(cutaneous/nasal).  Staphylococcus  
can  multiply  at  a  wide  range  of  temperatures,  thus,  if  food  is  left  to  cool  slowly  and  
remains  at  room  temperature  after  cooking,  the  organisms  will  have  opportunity  to  form  
enterotoxin.  Staphylococcal  food  poisoning  is  caused  by  eating  food  containing  one/more  
heat-­‐stable  polypeptide  enterotoxins  of  S.  aureus  
 
 
 
Pathogenesis  
Enterotoxins-­‐induced  gastroenteritis  is  further  defined  by  a  characteristic  set  of  histological  
abnormalities.  Inflammation  changes  are  observed  in  several  areas  of  GIT,  but  the  most  
severe  lesions  appear  in  the  stomach  and  upper  part  of  small  intestine.  These  areas  exhibit  
hyperemic  mucosa  with  neutrophilic  infiltrates  in  the  epithelium  and  the  underlying  lamina  
propria.  A  mucopurulent  exudate  is  observed  in  lumen  of  duodenum.  In  jejunum,  there  is  
crypt  extension  and  disruption/loss  of  brush  border.  Extensive  infiltrates  of  neutrophils  and  
macrophages  appear  in  the  lamina  propria  of  the  jejunum.  
 
 
 
Clinical  Picture  
Food  poisoning  is  caused  by  ingestion  of  any  enterotoxin  produced  by  S.  aureus  in  
contaminated  food  before  it’s  eaten.  The  presence  of  enterotoxins  in  food  vector  before  its  
consumption  accounts  for  short  incubation  period  of  this  illness.  Poisoning  begins  abruptly  
with  nausea,  vomiting,  crampy  abdominal  pain  and  diarrhea.  The  diarrhea  is  usually  non-­‐
inflammatory  and  is  of  lower  volume  than  that  in  cholera/toxigenic  E.  coli  infection.  Fever  
and  rash  are  absent,  and  patient  is  neurologically  normal.  Majority  of  cases  are  self-­‐limited  
and  resolve  between  8-­‐24  hours  after  onset.    Hypovolemia  and  hypotension  can  develop  in  
severe  cases.  
 
 
Food  Poisoning  by  Bacillus  cereus  
2  distinct  food  poisoning  syndromes  are  caused  by  this  organism.  First  one,  attributed  to  a  
heat-­‐stable  toxin,  causes  nausea  and  vomiting  approximately  6  hours  after  eating  toxin-­‐
contaminated  food.  The  other  type  is  caused  by  consuming  food  that  is  contaminated  with  
heat-­‐labile  enterotoxin.  In  this  type  of  food  poisoning,  diarrhea  occurs  approximately  12  
hours  after  eating  toxin-­‐containing  food.  Both  of  these  syndromes  result  from  initial  
contamination  of  food  by  B.  cereus  spores,  subsequent  growth  in  food,  and  toxin  produced  
by  it.  Growth  in  food  can  usually  be  inhibited  by  refrigeration,  although  some  strains  can  
grow  slowly  at  4°C.  Frying  may  not  destroy  the  heat-­‐stable  toxin.  
 
 
 
Food  Poisoning  by  Clostridium  perfringes  
1. intestinal  syndromes(food  poisoning,  enteritis  necroticans,  antibiotic-­‐associated  colitis)  
2. suppurative  deep  tissue  infections  
3. skin  and  soft  tissue  infections  
4. bacteremia  
 
Enterotoxin  is  the  best  understood  of  the  major  virulence  attributes  of  C.  perfringes.  
Production  of  enterotoxin  is  co-­‐regulated  with  sporulation;  the  toxin  is  released  upon  lysis  
of  vegetative  cell.  Proteolytic  removal  of  24  N-­‐terminal  amino  acids  from  toxin  activates  
molecule  which  then  consists  of  a  cytotoxic  N-­‐terminal  domain  and  a  C-­‐terminal  domain  
with  receptor  activity.  Although  traditionally  associated  with  strains  of  type  A,  enterotoxin  
and  its  genes  have  been  demonstrated  in  strains  of  other  types.  
Food  poisoning  is  caused  by  2  species  of  Clostridium:  C.  perfringes  and  C.  botulinum.  Food  
poisoning  caused  by  C.  perfringes  is  the  2nd/3rd  most  common  cause  of  food  poisoning  in  
Western  countries.  
 
 
 
Epidemiology  
-­‐ healthy  humans  serve  as  a  rich  reservoir  for  genes  coding  enterotoxin  C.  perfringes  type  
A  and  may  play  a  role  in  the  etiology  of  GI  diseases  caused  by  this  organism.  Humans  
should  be  considered  a  risk  factor  for  spread  of  C.  perfringes  type  A  food  poisoning  and  
that  they  are  a  possible  source  of  contamination  
-­‐ food  poisoning  occurs  after  ingesting  food  heavily  contaminated  with  vegetative  forms  of  
bacterium.  These  organisms  develop  from  C.  perfringes  spores  contaminating  the  food;  
refrigeration  inhibits  their  proliferation.  After  ingestion  of  contaminated  food,  C.  
perfringes  sporulate  in  lumen  of  small  intestine.  The  bacteria  cells  then  lyse,  releasing  
spores  and  enterotoxin,  a  protein  responsible  for  symptoms  of  this  type  of  food  
poisoning  
 
 
 
Clinical  Picture  
-­‐ food  poisoning  due  to  C.  perfringes  also  has  a  slightly  larger  incubation  period(8-­‐24  
hours)  and  results  from  survival  of  heat-­‐resistant  spores  in  inadequately  cooked  meat,  
poultry  or  legumes.  Symptoms  of  food  poisoning  from  type  A  strains  develop  8-­‐24  hours  
after  ingestion  of  food  heavily  contaminated  with  organism.  After  ingestion,  toxin  is  
produced  in  intestinal  tract  
-­‐ primary  symptoms  include  epigastric  pain,  nausea  and  watery  diarrhea  usually  lasting  
12-­‐24  hours.  Fever  and  vomiting  are  uncommon.  Diarrhea  appears  to  be  cause  by  a  heat-­‐
labile  protein  enterotoxin.  The  enterotoxin  inhibits  glucose  transport,  damages  intestinal  
epithelium  and  causes  protein  loss  into  the  intestinal  lumen  
Bacterial  Causes  of  Food  Poisoning  
Organisms   Major  Food  Source(s)   Toxin  In  Food   Ingestion  of  
Bacteria  
B.  cereus        
-­‐  heat-­‐stable  toxin   Fried  rice   Yes   No  
-­‐  enterotoxin   Meat  products   Yes   No  
S.  aureus   Cooked  meat,  cheese,   Yes   No  
pasta,  cream,  custard  pies  
C.  perfringes   Cooked  meat,  vegetable   No   Releases  
soup  prepared  in  bulk   enterotoxin  
in  intestine;  
Yes  
S.  enteritidis/typhimurium   Raw  eggs,  mayonnaise,   No   Yes  
incompletely  cooked  meat  
Shigella  spp   Food  contaminated   No   Yes  
during  preparation  
Campylobacter  jejuni   Incompletely  cooked   No   Yes  
meat,  raw  milk  
 
Foodborne  Illnesses(Bacterial)  
Etiology   Incubation   Signs  and   Duration   Laboratory  Testing   Treatment  
period   Symptoms   of  Illness  
B.  cereus   10-­‐16   Abdominal   24-­‐48   Testing  not   Supportive  
(diarrheal   hours   cramps,   hours   necessary;  self-­‐ care,  self-­‐
toxin)   watery   limiting  (consider   limiting  
diarrhea,   testing  food  and  
nausea   stool  for  toxins  in  
outbreak)  
Preformed   1-­‐6  hours   Sudden  onset   24  hours   Normally  a  clinical   Supportive  
enterotoxi of  severe   diagnosis.  Clinical   care  
n   nausea  and   labs  don’t  routinely  
vomiting.   identify  this  
Diarrhea  may   organism.  If  
be  present   indicated,  send  stool  
and  food  specimens  
to  reference  lab  for  
culture  and  toxin  
identification  
C.   8-­‐16  hours   Watery   24-­‐48   Stools  can  be  tested   Supportive  
perfringes   diarrhea,   hours   for  enterotoxin  and   care;  
toxin   nausea,   cultured  for   Antibiotics  
abdominal   organism.   not  
cramps.   Quantitative   indicated  
Fever  is  rare   cultures  must  be  
done  because  C.  
perfringes  can  
normally  be  found  in  
stool  
S.  aureus   1-­‐6  hours   Sudden  onset   24-­‐48   Normally  a  clinical   Supportive  
enterotoxi of  severe   hours   diagnosis.  Vomitus   care  
n   nausea  and   and  food  can  be  
vomiting,   tested  for  toxin  and  
abdominal   cultured  if  indicated  
cramps.  
 Fever  may  be  
present  
Etiology   Incubation   Signs  and   Duration   Laboratory  Testing   Treatment  
period   Symptoms   of  Illness  
Salmonella   1-­‐3  days   Diarrhea,   4-­‐7  days   Routine  stool    
spp   fever,   cultures  
abdominal  
cramps,  
vomiting  
Entero-­‐ 1-­‐3  days   Watery   3-­‐7  days   Stool  culture.  ETEC   Supportive  
toxigenic   diarrhea,   requires  special  lab   care;  
E.   abdominal   techniques  for   Antibiotics  
coli(ETEC)   cramps,  some   identification.  If   rarely  
vomiting   suspected,  must   needed  
request  special   expect  in  
testing   severe  
cases  
 
 
 
Characteristics  of  Selected  Foodborne  Illnesses  
Organism   Vomiting   Diarrhea   Fever   Other  Symptoms  
S.  aureus   +++   ++   -­‐    
B.  cereus   +++   +   -­‐    
(emetic  
syndrome)  
B.  cereus   +   +++   -­‐   Abdominal  cramps  
(diarrheal  
syndrome)  
C.  perfringes   +   +++   -­‐   Abdominal  cramps  
Salmonella  spp   +   +++   ++   Abdominal  cramps,  headache,  
myalgias  
Norwalk  virus   +++   +++   ++   Headaches,  myalgias  
Histamine  fish   +   +++   -­‐   Headache,  flushing,  urticaria  
poisoning  
(Scomboid)  
Ciguatera   +   ++   -­‐   Paraesthesias,  myalgias,  headache,  
arthralgia  
 
 
 
Clinical  Disease  Caused  by  Enterotoxigenic  and  Invasive  Organisms  
Enterotoxigenic   Invasive  
Severe  watery  diarrhea,  no  dysentery   Dysentery(blood,  mucosa,  
polymorphonuclear  leukocytes)  
No  Fever   Fever  
No  systemic  toxicity   Severe  systemic  toxicity  
Little  abdominal  pain  and  cramping   Severe  abdominal  pain  and  cramping  
tenesmus  
Bacteria  multiply  in  small  bowel   Bacteria  multiply  in  colon  
No  polymorphonuclear  leukocytes  in  stool   PMN  leukocytes  in  stool  
Respond  to  non-­‐absorbable  antimicrobial   Respond  to  absorbable  and  parenteral  
agents   antibiotics  
Complications  of  Food  Poisoning  
Infection   Complications   Complications(%)   Isolation  Needed  
B.  cereus  toxin   Dehydration,  occasional   Unusual   No  
(rapid)   shock  
B.  cereus  toxin   No  direct  complications   -­‐   No  
(late)  
Staphylococcal   Shock,  occasional  death   <1%   No  
toxin  
C.  perfringes   Dehydration,  occasional   Elderly  and   Yes  
death   compromised  
Salmonellosis   Sepsis,  reactive  arthritis,   5%  sepsis,  2%   Yes  
distant  focal  collection,   reactive  arthritis  
osteomyelitis  in  sickle  cell  
disease,  meningitis  in  infants  
Campylobacter   Prolonged  symptom,   10-­‐20%  ill  for  >1   Yes  
spp   potential  for  relapse,   week,  5-­‐10%  
bacteremia,  focal  sepsis,   relapse,  bacteremia  
rarely  Guillain-­‐Barre   in  <1%  
syndrome