Epidemiology of Pediatric Diarrheal Diseases
1.7 billion cases of childhood diarrheal diseases each year
Leading cause of malnutrition in children <5 years old
2nd leading cause of mortality in children <5 years old
Secretory Gastroenteritis
Proximal small intestine
Watery diarrhea
No fecal leukocytes
Mechanism: enterotoxin (produced in or affecting intestines) or bacterial adherence/invasion causes shift in water and electrolyte excretion/adsorption
Classic pathogens: Vibrio cholerae ETEC Clostridium perfringens Staphyloccocus aureus Bacillus cereus
Inflammatory Gastroenteritis
Colon (large intestine)
Dysentery
Fecal polymorhonuclear leukocytes
Bacterial invasion or cytotoxins cause mucosal damage that leads to inflammation
Classic pathogens: Shigella EHEC Salmonella (not S. Typhi/Paratyphil) Campylobacter
Invasive Gastroenteritis
Distal small intestine
Enteric fever (Typhoid fever)
Fecal mononuclear leukocytes
(if a patient has diarrhea)
Bacteria penetrate mucosa and invade the reticuloendothelial system
Classic pathogens:
Salmonella S. Typhi/Paratyphil
Yersinia enterocolitica
Enterobacteriaceae
Enteric bacteria or Enterics
Ubiquitous (GI, soil, plants): simple nutritional requirements
Primary pathogens
Opportunistic pathogens
Gram-negative rods Non-sporeforming Facultative anaerobes Growth on McConkey agar Ferment glucose Reduce nitrate Catalase-positive Oxidase-negative
Clinical significance?
Sorbitol MacConkey (SMAC)
Used for Gram- enteric rods
Contains bile salts and crystal violet to SUPPRESS Gram+ bacteria
Lactose+ (pink/purple) [E. Coli, Klebsiella]
Lactose- (colorless) [Salmonella, Shigella, Proteus]
Escherichia coli
Agent for:
Diarrhea, UTI, meningitis, HUS, septicemia, pneumonia
Different strains associated with different diseases
Serotype classification useful in epidemiology: Somatic O antigen Flagellar H protein Capsular K antigens Ex. E. coli O157:H7
Virotypes based on virulence factors present in a particular strain
Ferments lactose
Etiology and symptoms of HUS
Hemolytic Uremic Syndrome
Occurs in 10% of children <10 years old who are infected with EHEC
Death occurs in 3-5% of HUS patients
Toxemia affecting the kidney
Anemia, thrombocytopenia, acute renal failure due to microthrombi forming on damaged endothelium
> Mechanical hemolysis > Platelet consumption > Decreased renal flow
Enterohemorrhagic E. coli (EHEC)
Hemorrhagic, Hamburgers, HUS
EHEC Virulence Factors
Virulence factors transmitted by bacteriophages: take the virulent and spread to non-virulent colonies
Inject shiga toxins
Enterotoxigenic E. coli (ETEC)
Pathogenesis: due to enterotoxins
No histological changes or inflammation
ETEC Virulence Factors (Adhesins and Exotoxins)
Type 1 pili
1. Fimbriae:
Colonization factor antigens (CFAs)
Located on plasmids
LT and ST; LT is 75% similar to cholera toxin, with the same mechanism of action
ETEC Heat-labile toxin
Heat-Labile Toxin (LT-1)
A1B5 toxin and homologous to cholera toxin
ETEC Heat-stable toxin
Methanol-soluble ST (STa)
Family of SMALL PEPTIDE toxins
1. Binds and activates host guanylate cyclase (GC)
2. cGMP levels increase
3. Affects many cellular functions including ion transport
EPEC
EAEC
DAEC
EIEC
Epithelial cell destruction > inflammatory infiltration > colonic ulceration
**Related to Shigella, but require higher inoculum because aren’t pH resistant
DO NOT produce Shiga toxin
E. Coli Prevention and Treatment
Avoid contaminated foods and water
No medium to rare burgers
Fluid and electrolyte maintenance
HUS: dialysis and blood transfusions
Antibiotics not normally use since infections are mostly self limited (resolved without treatment)
Strains usually resistant to multiple drugs
Salmonella
Salmonellosis
1. Contaminated food (poultry, eggs) causes S. typhimurium
Commensals of a wide variety of domestic and wild animals
Common cause of diarrhea in US
DNA hybridization: strains are closely related
> 2400 O serogroups; variations in the distal end of the LPS
Biochemical tests:
Lactose-negative (in contrast to E. coli; unable to ferment lactose)
Salmonella Typhoid (Enteric) Fever
Salmonella Virulence factors
Fimbrial adhesions, some encoded by plasmids
Facultative intracellular, replicates in phagosome
2 x T3SS: encoded by two separate pathogenecity islands (SPI-1 internalization, and SPI-2 block of phagosome-lysosome fusion)
Other SPIs - Mg2+ transporter (intravacuolar growth)
Protection against:
Endotoxin
Membrane ruffles
Endotoxins vs endotoxins
An exotoxin is a toxin secreted by bacteria. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host. Exotoxins may be secreted, or, similar to endotoxins, may be released during lysis of the cell.
Salmonella: Treatment and prevention
S. Typhoid usually requires antibiotics and vaccines: 1. Antibiotic Ciprofloxacin Levofloxacin Azithromycin (Asian) Cefriaxone (Asian) Carbapenem (critically ill)