gastrointestinal bacterial infections
DESCRIPTION
Gastrointestinal Bacterial Infections. Salmonella Shigella Yersinia enterocolitica. Liliana Rodríguez, MPH, RM (AAM), M(ASCP) UT Health Science Center at Houston [email protected]. Salmonella. Motile Gram-negative rods, members of the Family Enterobacteriaceae - PowerPoint PPT PresentationTRANSCRIPT
Gastrointestinal Bacterial Infections
SalmonellaSalmonella Shigella Shigella Yersinia enterocoliticaYersinia enterocolitica
Liliana Rodríguez, MPH, RM (AAM), M(ASCP)Liliana Rodríguez, MPH, RM (AAM), M(ASCP) UT Health Science Center at HoustonUT Health Science Center at Houston
[email protected]@uth.tmc.edu
Salmonella Motile Gram-negative rods, members of the Motile Gram-negative rods, members of the
Family Family EnterobacteriaceaeEnterobacteriaceae Common speciesCommon species
• S. cholerasuis (pigs) • S. typhimurium (cattle, pigs, poultry)• S. typhi, S. paratyphi A and B (humans)• S. enteritidis (1500 serotypes) many hosts
Non-lactose fermentors; production of HNon-lactose fermentors; production of H22SS
Laboratory Identification
Non-lactose fermenting colonies on MacConkey
agar
Biochemical reactions on TSI
Serotyping
Salmonella: Epidemiology
Ubiquitous pathogensUbiquitous pathogens All are associated with animals, except All are associated with animals, except S. S.
typhi, S. paratyphi typhi, S. paratyphi A, B, and CA, B, and C Transmitted to humans via contaminated Transmitted to humans via contaminated
food, water (less frequent), or person-to-food, water (less frequent), or person-to-personperson
Killed by gastric acidKilled by gastric acid High infectious doseHigh infectious dose
Virulence factors
Virulence polysaccharide (Vi antigen)Virulence polysaccharide (Vi antigen) Adhesion to M-cellsAdhesion to M-cells MotilityMotility Tolerance to acid in phagocytic cellsTolerance to acid in phagocytic cells Survival in macrophages (Survival in macrophages (S. typhiS. typhi)) Endotoxin Endotoxin
Salmonella: Clinical Syndromes
1.1. GastroenteritisGastroenteritis
2.2. Extra-intestinalExtra-intestinal SepticemiaSepticemia Typhoid fever (enteric fever)Typhoid fever (enteric fever) Chronic carriageChronic carriage
Gastroenteritis Most common Most common
manifestationmanifestation Highest rates of infection Highest rates of infection
in childrenin children S. enteritidis S. enteritidis (many (many
serotypes)serotypes) Contaminated food - Contaminated food -
eggs, poultry, dairyeggs, poultry, dairy Exotic petsExotic pets Incubation period 12-48 Incubation period 12-48
hrshrs
Gastroenteritis PathogenesisAttachment to the brush border
Ruffles
Invasion and penetration of enterocytes
←
bacterial death
Inflammatory Response
PMN confine infection to GI tractPMN confine infection to GI tract Mediates release of prostaglandinsMediates release of prostaglandins Stimulates cAMP, activates fluid secretion Stimulates cAMP, activates fluid secretion
resulting in diarrhearesulting in diarrhea S. enteritidisS. enteritidis can become can become invasiveinvasive in in
immunocompromised patientsimmunocompromised patients
Salmonella enteritis ingestion
diarrhea
bacteria penetrate cells and migrate to lamina propria layer of ileoceal region
multiply in lymphoid follicles causing reticuloendothelial hyperplasia and hypertrophy
polymorphonuclear leucocytes confine infection to GI tract
inflammatory response also mediates release of prostaglandins
stimulates cAMP and active fluid
secretion
absorbed to epithelial cells in terminal portion of small intestine
Summary
Gastroenteritis: Clinical Presentation
Nausea, vomiting (rare)Nausea, vomiting (rare) Fever (50%)Fever (50%) Abdominal crampsAbdominal cramps Acute but self-limiting watery or bloody Acute but self-limiting watery or bloody
diarrhea with fecal leukocytesdiarrhea with fecal leukocytes Symptoms subside in 7 days, but stool Symptoms subside in 7 days, but stool
cultures remain (+) several weekscultures remain (+) several weeks
Bacteremia Caused by salmonellas Caused by salmonellas
highly adapted to animals:highly adapted to animals: S. cholerasuisS. cholerasuis S. typhimuriumS. typhimurium S. enteritidis S. enteritidis
heidelbergheidelberg Severe disease in humansSevere disease in humans Portal of entry: GI tract Portal of entry: GI tract Phagocytes in lamina Phagocytes in lamina
propria cannot stop propria cannot stop infectioninfection
Pathogenesis
Bacteremia: Pathogenesis
Penetrates mucosa - invades bloodstreamPenetrates mucosa - invades bloodstream Localizes in abnormal cardiovascular Localizes in abnormal cardiovascular
surfaces of some patients (It has a surfaces of some patients (It has a predilection for the artherosclerotic plaque)predilection for the artherosclerotic plaque)
It can cause metastasic infection in bones It can cause metastasic infection in bones (osteomyelitis)(osteomyelitis)
Sepsis can be seen in those with cell-Sepsis can be seen in those with cell-mediated immune system deficienciesmediated immune system deficiencies
Clinical Presentation High fever without localizing findingsHigh fever without localizing findings Minimal or absent GI symptoms Minimal or absent GI symptoms MeningitisMeningitis ArthritisArthritis EndocarditisEndocarditis
Typhoid Fever
Systemic infection of mononuclear phagocytesSystemic infection of mononuclear phagocytes Etiologic agentEtiologic agent:: S. typhi S. typhi Parathypoid feverParathypoid fever caused by S. caused by S. paratyphi A,paratyphi A, S. scottmulerii S. scottmulerii (paratyphi(paratyphi B) and B) and S. hirschfeldiiS. hirschfeldii
(paratyphi C)(paratyphi C) Humans-humans (no animal reservoir)Humans-humans (no animal reservoir) S. typhiS. typhi virulence virulence
• binds to intestinal M-cells (adhesin)binds to intestinal M-cells (adhesin)• motilitymotility• intracellularityintracellularity
Typhoid Fever: Pathogenesis
Infective dose: 10Infective dose: 1055
Penetration of gut mucosa (jejunum, ileum)Penetration of gut mucosa (jejunum, ileum)
Reaches intestinal lymph nodes, survives Reaches intestinal lymph nodes, survives and multiply within macrophagesand multiply within macrophages
Typhoid Fever: Pathogenesis
After 5-7 days reaches blood, taken up by After 5-7 days reaches blood, taken up by liver, bone marrow, and spleen, where liver, bone marrow, and spleen, where intracellular replication continues intracellular replication continues (asymptomatic incubation period)(asymptomatic incubation period)
Multiplication within macrophages Multiplication within macrophages continues continues → → release into the bloodstreamrelease into the bloodstream
Resolves, gets complicated, or patient Resolves, gets complicated, or patient becomes a chronic carrier (becomes a chronic carrier (1-3 %) 1-3 %)
Typhoid Fever: Pathogenesis
Typhoid Fever: Clinical Manifestations
Incubation period: 1-2 weeks after Incubation period: 1-2 weeks after ingestioningestion
A sustained period of high fever (4-8 A sustained period of high fever (4-8 weeks if untreated)weeks if untreated)
Malaise, achesMalaise, aches Respiratory symptoms (flu-like) Respiratory symptoms (flu-like) Occasional diarrhea or constipationOccasional diarrhea or constipation Rose spots (50%)Rose spots (50%)
Diagnosis GastroenteritisGastroenteritis
• Stool cultureStool culture• Biochemical idBiochemical id
BacteremiaBacteremia• Blood culturesBlood cultures• Stool cultures usually Stool cultures usually
negativenegative• Leukocytosis (many WBC)Leukocytosis (many WBC)
Diagnosis of Typhoid Fever
Clinical historyClinical history Blood cultures Blood cultures
during the first 2 during the first 2 weeksweeks
Stool and urine Stool and urine culture during weeks culture during weeks 3-43-4
Bone marrowBone marrow aspiration if neededaspiration if needed
Serology: Widal test
The Widal test measures the patient’s antibodies against Salmonella typhi “O” and “H” antigen preparations. Dilutions 1:20-1:1280 and negative control. In this case “O” antigen titer = 1:80.
1:20 1:40 1:80
Salmonella Infections: Therapy
SyndromeAntibioticsIndicated
Useful Antibiotics
Enterocolitis No
Yes
Yes
ImmunosuppressionDebilitated hostInfants, elderly
Chronic bacteremiaExtra-intestinal infectionTyphoid fever
AmpicillinChloramphenicolTrimethoprimCiprofloxacinCeftriaxone
Prevention
Hand washingHand washing Adequate standards of Adequate standards of
public health and public health and educational programseducational programs
Food workers should Food workers should be excluded from be excluded from handling foodhandling food
Prolonged treatment Prolonged treatment for chronic carriersfor chronic carriers
Prevention Typhoid fever immunizationTyphoid fever immunization
• inactivated –parenteralinactivated –parenteral• live – orallive – oral• Vi antigen- parenteralVi antigen- parenteral
Preventing gastroenteritis presents a Preventing gastroenteritis presents a challenge because of animal reservoirschallenge because of animal reservoirs
Shigella Closely related to Closely related to E. coliE. coli Non-lactose fermenterNon-lactose fermenter No gas from glucoseNo gas from glucose Non-motileNon-motile Causes bacillary dysenteryCauses bacillary dysentery
Stool Gram stain showing numerous white blood cells and GNR
Shigella: Classification
Group
A
B
C
D
Species
S. dysenteriae
S. flexneri
S. boydii
S. sonnei
Shigella species S. S. dysenteriae dysenteriae (Shiga bacillus) (Shiga bacillus) first discovered in 1890 Japan; re-first discovered in 1890 Japan; re-
emerged in 1969emerged in 1969 causes most serious diseasecauses most serious disease S.S. dysenteriae type 1 produces Shiga toxin (cytotoxin) type 1 produces Shiga toxin (cytotoxin) associated with 10-20% mortalityassociated with 10-20% mortality
S. flexneriS. flexneri is the dominant species internationally. Associated with is the dominant species internationally. Associated with severe infections in gay man.severe infections in gay man.
Shigella species cont..
SS. boydii. boydii causes severe infections. Occurs primarily in India causes severe infections. Occurs primarily in India S. soneiiS. soneii is the most important in the United States (70% of the cases). is the most important in the United States (70% of the cases).
Shigellosis in the U.S. is primarily a pediatric diseaseShigellosis in the U.S. is primarily a pediatric disease Species distinguished from one another by serology, not Species distinguished from one another by serology, not
biochemically.biochemically.
Epidemiology
Humans only reservoirHumans only reservoir Spread from person-to-person by the fecal-oral routeSpread from person-to-person by the fecal-oral route Extremely low infective dose (10-100 cells)Extremely low infective dose (10-100 cells) No seasonal incidence for isolated causesNo seasonal incidence for isolated causes Epidemics occur in the summerEpidemics occur in the summer The most virulent of all enteric pathogensThe most virulent of all enteric pathogens
Age distribution of diarrheal disease caused by Campylobacter, Salmonella, and Shigella
Shigella: Virulence Factors
Gastric acid resistantGastric acid resistant Attachment – invasion plasmid antigens (Ipa) Attachment – invasion plasmid antigens (Ipa) Intracellular pathogen (local invasion)Intracellular pathogen (local invasion) ToxinsToxins
• cytotoxins – “Shiga” toxin (cytotoxins – “Shiga” toxin (S. dysenteriae)S. dysenteriae)• enterotoxins role unknownenterotoxins role unknown
Shigella: Local Invasion
Shigella: Pathogenesis
Attachment and invasion of mucosal Attachment and invasion of mucosal epithelium of distal ileum and colonepithelium of distal ileum and colon
Destruction of enterocytes and release of Destruction of enterocytes and release of TNF, PGTNF, PG
Vascular abnormalitiesVascular abnormalities Locally invasiveLocally invasive Rarely invade bloodstream (except Rarely invade bloodstream (except S. S.
dysenteriaedysenteriae type 1) type 1)
Shigella
Shigella: Clinical Features
Incubation period 1-2 daysIncubation period 1-2 days Mild diarrhea to dysenteryMild diarrhea to dysentery Diarrhea, abdominal cramps, fever, malaise, Diarrhea, abdominal cramps, fever, malaise,
anorexia, and sometimes myalgiasanorexia, and sometimes myalgias Stool contains mucus and blood. Most Stool contains mucus and blood. Most
display many white blood cellsdisplay many white blood cells Self-limiting but dehydration can occur, Self-limiting but dehydration can occur,
especially in the young and elderlyespecially in the young and elderly No chronic carrier stateNo chronic carrier state
Shigella: Diagnosis Rectal swabs or stoolRectal swabs or stool Requires transport mediaRequires transport media Fecal leukocytes (+)Fecal leukocytes (+) CultureCulture Biochemical testsBiochemical tests Agglutination testsAgglutination tests Other: PCR, DNA probesOther: PCR, DNA probes
Shigella on MacConkey Agar
Non-lactose fermenter Non-motile
Shigellosis: Prevention
Education in personal Education in personal hygienehygiene
Proper disposal of Proper disposal of diapers at day-care diapers at day-care centerscenters
Hand-washing Hand-washing Safe sex for gay manSafe sex for gay man
Yersinia enterocolitica: “the cold bug”
Gram negative Gram negative encapsulated encapsulated cocobacillus with polar cocobacillus with polar stainingstaining
Prefers to grow Prefers to grow between 22-25 between 22-25 ººCC
Requires a special Requires a special medium to growmedium to grow
Y. enterocolitica: Epidemiology Food-associated infection in Food-associated infection in coldercolder parts of parts of
the worldthe world More common during More common during coldercolder months months Found in rodents, rabbits, pigs, sheep, Found in rodents, rabbits, pigs, sheep,
cattle, horses, dogs.cattle, horses, dogs. Humans are accidental hostsHumans are accidental hosts Survives and multiplies at refrigerator Survives and multiplies at refrigerator
temperaturestemperatures
Y. enterocolitica: Virulence Factors
Invasin - early attachment protein to cells Invasin - early attachment protein to cells expressing receptorexpressing receptor
ST-like enterotoxin (chromosomal)ST-like enterotoxin (chromosomal)
Complement resistance factorComplement resistance factor
Yersinia outer proteins or Yersinia outer proteins or YopsYops (anti- (anti-phagocytic & toxic action)phagocytic & toxic action)
Y. enterocolitica: Pathogenesis
Invasion of M-cells of Peyer’s patchesInvasion of M-cells of Peyer’s patches
In contrast to Shigella, Yersinia does not In contrast to Shigella, Yersinia does not replicate in the M-cells but passes to the replicate in the M-cells but passes to the underlying tissueunderlying tissue
Engulfed by macrophages and carried to Engulfed by macrophages and carried to MLN where they replicateMLN where they replicate
Y. enterocolitica: Clinical Syndromes
Enterocolitis - young children.Enterocolitis - young children.
Mesenteric adenitis (Mesenteric adenitis (mimics appendicitismimics appendicitis) - ) - older children.older children.
Focal necrosis of Peyer’s patches.Focal necrosis of Peyer’s patches.
Bacteremia - high fatality rate.Bacteremia - high fatality rate.
Arthritis, reactive polyarthritis (post-Arthritis, reactive polyarthritis (post-infection in adults)infection in adults)
Y. enterocolitica: Diagnosis Challenging - few Challenging - few
laboratories screen laboratories screen for for YersiniaYersinia
Can be isolated from Can be isolated from stoolstool
Non-lactose Non-lactose fermenterfermenter
Cold enrichmentCold enrichment increases chances of increases chances of isolationisolation
Y. enterocolitica: Treatment
Usually self-limitingUsually self-limiting Not clear if antibiotics helpNot clear if antibiotics help If needed, aminoglycosides, tetracycline, If needed, aminoglycosides, tetracycline,
chloramphenicol and broad-spectrum chloramphenicol and broad-spectrum cephalosporins cephalosporins
Resistant to ampicillin and cephalosporins Resistant to ampicillin and cephalosporins (beta-lactamase)(beta-lactamase)