Yersinia 2007

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YersiniaYersinia

Are short, pleomorphic gram Are short, pleomorphic gram negative rods that can exhibit negative rods that can exhibit bipolar stainingbipolar staining

Are catalase positive, oxidase Are catalase positive, oxidase negative and microaerophilic or negative and microaerophilic or facultative anaerobicfacultative anaerobic

Most have animals as their natural Most have animals as their natural hosts, but they can produce hosts, but they can produce serious human disease in humansserious human disease in humans

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YersiniaYersinia

The genus includes:The genus includes: Yersinia pestisYersinia pestis – plague – plague Yersinia pseudotuberculosisYersinia pseudotuberculosis and and

Yersinia enterocoliticaYersinia enterocolitica – human – human diarrhoeal diseasesdiarrhoeal diseases

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Yersinia PestisYersinia Pestis

Gram negative rod with striking Gram negative rod with striking bipolar staining with special stainsbipolar staining with special stains

NonmotileNonmotile Grows as facultative anaerobe on Grows as facultative anaerobe on

many bacteriologic mediamany bacteriologic media Growth is more rapid in media Growth is more rapid in media

containing blood or tissue fluids containing blood or tissue fluids and fastest at 30 and fastest at 30 CC

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In cultures of blood agar at 37 In cultures of blood agar at 37 C, C, colonies may be very small at 24 colonies may be very small at 24 hourshours

A virulent inoculum, derived from A virulent inoculum, derived from infected tissue, produces gray and infected tissue, produces gray and viscous colonies but after passage viscous colonies but after passage in the laboratory the colonies in the laboratory the colonies become irregular and rough become irregular and rough

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Has little biochemical activity, is Has little biochemical activity, is somewhat variablesomewhat variable

Antigenic structureAntigenic structure All yersiniae possess All yersiniae possess

lipopolysaccharides that have lipopolysaccharides that have endotoxic activity when releasedendotoxic activity when released

Produce many antigens and toxins Produce many antigens and toxins that act as virulence factorsthat act as virulence factors

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The envelope contains a protein The envelope contains a protein (fraction I) produced mainly at (fraction I) produced mainly at 37 37 C and confers antiphagocytic C and confers antiphagocytic propertiesproperties

Virulent, wild-type Virulent, wild-type Y. pestisY. pestis carries carries V-W antigens, which are encoded V-W antigens, which are encoded by genes on plasmidsby genes on plasmids

A 72-kb plasmid is essential for A 72-kb plasmid is essential for virulencevirulence

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Avirulent strains lack the plasmidAvirulent strains lack the plasmid Some stable avirulent strains Some stable avirulent strains

have served as live vaccineshave served as live vaccines Produces coagulase at 28 Produces coagulase at 28 C C

(normal temperature of the flea) (normal temperature of the flea) but not at 35 but not at 35 C (transmission via C (transmission via fleas is low or absent in very hot fleas is low or absent in very hot weather) weather)

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Among several exotoxins Among several exotoxins produced, one is lethal for mice produced, one is lethal for mice in amounts of 1 in amounts of 1 µµgg

This homogenous protein (MW This homogenous protein (MW 74,000) produces beta-74,000) produces beta-adrenergic blockage and is adrenergic blockage and is cardiotoxic in animalscardiotoxic in animals

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Its role in human infection is unknownIts role in human infection is unknown Produces a bacteriocin (pesticin); the Produces a bacteriocin (pesticin); the

enzyme isocitrate lyase which is said enzyme isocitrate lyase which is said to be distinctive and other productsto be distinctive and other products

Some antigens cross-react with other Some antigens cross-react with other yersiniaeyersiniae

Bacteriophage may lyse other Bacteriophage may lyse other yersiniaeyersiniae

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Pathogenesis and PathologyPathogenesis and Pathology When a flea feeds on a rodent When a flea feeds on a rodent

infected with infected with Y. pestisY. pestis, the , the ingested organisms multiply in ingested organisms multiply in the gut of the flea and helped by the gut of the flea and helped by coagulase, block its coagulase, block its proventriculus so that no food proventriculus so that no food can pass throughcan pass through

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Subsequently the blocked and Subsequently the blocked and hungry flea bites ferociuosly and the hungry flea bites ferociuosly and the aspirated blood contaminated with aspirated blood contaminated with Y. Y. pestis pestis from the flea, is regurgitated from the flea, is regurgitated into the bite woundinto the bite wound

Inoculated organisms may be Inoculated organisms may be phagocytosed by polymorphonuclear phagocytosed by polymorphonuclear cells and monocytescells and monocytes

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The organisms are killed by the The organisms are killed by the polymorphonuclear cells but can polymorphonuclear cells but can multiply in the monocytes multiply in the monocytes because bacteria are multiplying because bacteria are multiplying at 37 at 37 C, they produce C, they produce antiphagocytic proteins and antiphagocytic proteins and subsequently are able to resist subsequently are able to resist phagocytosisphagocytosis

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The pathogens rapidly reach the The pathogens rapidly reach the lymphatics and an intense lymphatics and an intense hemorrhagic inflammation hemorrhagic inflammation develops in the enlarged lymph develops in the enlarged lymph nodes, may undergo necrosis nodes, may undergo necrosis and become fluctuantand become fluctuant

Often reach bloodstream and Often reach bloodstream and become widely disseminatedbecome widely disseminated

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Hemorrhagic and necrotic lesions may Hemorrhagic and necrotic lesions may develop in all organsdevelop in all organs

Meningitis, pneumonia and Meningitis, pneumonia and serosanguineous pleuropericarditis are serosanguineous pleuropericarditis are prominent featuresprominent features

Primary pneumonic plague results Primary pneumonic plague results from inhalation of infective drops (from from inhalation of infective drops (from a coughing patient), with hemorrhagic a coughing patient), with hemorrhagic consolidation, sepsis and deathconsolidation, sepsis and death

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Clinical FindingsClinical Findings AfterAfter an IP of 2 – 7 days, there is an IP of 2 – 7 days, there is

high fever and painful high fever and painful lymphadenopathy commonly with lymphadenopathy commonly with greatly enlarged, tender nodes greatly enlarged, tender nodes (buboes) in the groin or axillae(buboes) in the groin or axillae

Vomiting and diarrhoea may Vomiting and diarrhoea may develop with early sepsisdevelop with early sepsis

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Later, DIC leads to hypotension, Later, DIC leads to hypotension, altered mental status, renal and altered mental status, renal and cardiac failurecardiac failure

Terminally, signs of pneumonia Terminally, signs of pneumonia and meningitis can appearand meningitis can appear

Y. pestisY. pestis multiplies multiplies intravascularly and can be seen intravascularly and can be seen in blood smearsin blood smears

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Diagnostic Lab TestsDiagnostic Lab Tests Plague should be suspected in febrile Plague should be suspected in febrile

patients who have been exposed to patients who have been exposed to rodents in known endemic areasrodents in known endemic areas

Rapid recognition and lab Rapid recognition and lab confirmation of disease are essential confirmation of disease are essential in order to institute lifesaving in order to institute lifesaving therapytherapy

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SpecimensSpecimens Blood for cultureBlood for culture Aspirates of enlarged lymph Aspirates of enlarged lymph

nodes for smear and culturenodes for smear and culture Acute and convalescent sera for Acute and convalescent sera for

antibody levelsantibody levels Sputum for cultureSputum for culture CSF for smear and cultureCSF for smear and culture

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SmearsSmears Examined after staining with Examined after staining with

Giemsa’s stain and with specific Giemsa’s stain and with specific immunofluorescent stainsimmunofluorescent stains

With Wayson’s stain, may show With Wayson’s stain, may show striking bipolar appearancestriking bipolar appearance

CSF and sputum smears should CSF and sputum smears should also be stainedalso be stained

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CultureCulture On BA, MCA plates and in infusion On BA, MCA plates and in infusion

brothbroth Growth on solid media may be Growth on solid media may be

slow but blood culture are often slow but blood culture are often +ve in 24 hrs+ve in 24 hrs

Tentatively identified by Tentatively identified by biochemical reactionsbiochemical reactions

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Yersinia PestisYersinia Pestis Definite identification is best done by Definite identification is best done by

immunofluorescenceimmunofluorescence All cultures are highly infectious and must All cultures are highly infectious and must

be handled with extreme cautionbe handled with extreme cautionSerologySerology In previously unvaccinated, a convalescent In previously unvaccinated, a convalescent

serum antibody titre of 1:16 or greater is serum antibody titre of 1:16 or greater is presumptive evidence of infectionpresumptive evidence of infection

A titre rise in two sequential specimens A titre rise in two sequential specimens confirms the serologic diagnosisconfirms the serologic diagnosis

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TreatmentTreatment Unless promptly treated, have a Unless promptly treated, have a

mortality rate of about 50%; mortality rate of about 50%; pneumonic plague nearly 100%pneumonic plague nearly 100%

Drug of choice is streptomycinDrug of choice is streptomycin Tetracycline is an alternative drug and Tetracycline is an alternative drug and

is sometimes given in combination is sometimes given in combination with streptomycinwith streptomycin

Drug resistance has not been reportedDrug resistance has not been reported

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Epidemiology and ControlEpidemiology and Control Plague is an infection of wild Plague is an infection of wild

rodents (field mice, gerbils, rodents (field mice, gerbils, moles, skunks, and other animals) moles, skunks, and other animals) that occurs in many parts of the that occurs in many parts of the worldworld

Chief enzootic areas are India, Chief enzootic areas are India, Southeast Asia (Vietnam), Africa, Southeast Asia (Vietnam), Africa, North and South AmericaNorth and South America

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The Western states of US and mexico The Western states of US and mexico alway contain reservoirs of infectionalway contain reservoirs of infection

Epizootics with high mortality rates Epizootics with high mortality rates occur intermitently; at such times, occur intermitently; at such times, the infection can spread to domestic the infection can spread to domestic rodents (rats) and other animals rodents (rats) and other animals (cats) and humans can be infected (cats) and humans can be infected by flea bites or by contactby flea bites or by contact

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The commonest vector is the rat flea The commonest vector is the rat flea Xenopsylla cheopis Xenopsylla cheopis but other fleas but other fleas may also transmit the infectionmay also transmit the infection

Control requires surveys of infected Control requires surveys of infected animals, vectors and human contactsanimals, vectors and human contacts

All patients with suspected plague All patients with suspected plague should be isolated particularly if should be isolated particularly if pulmonary involvement has not been pulmonary involvement has not been ruled out ruled out

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All specimens must be treated with All specimens must be treated with extreme cautionextreme caution

Contacts of patients with suspected Contacts of patients with suspected plague pneumonia should receive plague pneumonia should receive tetracycline as chemoprophylaxistetracycline as chemoprophylaxis

A formalin-killed vaccine is A formalin-killed vaccine is available for travelers to available for travelers to hyperendemic areas and for hyperendemic areas and for persons at special high riskpersons at special high risk

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Yersinia enterocolitica and Y. Yersinia enterocolitica and Y. pseudotuberculosispseudotuberculosis

Non-lactose fermenting gram Non-lactose fermenting gram negative rods that are urease-negative rods that are urease-positive and oxidase negativepositive and oxidase negative

Grow best at 25 Grow best at 25 C and are motile at C and are motile at

25 25 C but nonmotile at 37 C but nonmotile at 37 CC Found in intestinal tract of a variety Found in intestinal tract of a variety

of animals in which they cause of animals in which they cause diseasedisease

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and are transmissible to humans and are transmissible to humans in whom they can produce a in whom they can produce a variety of clinical syndromesvariety of clinical syndromes

Y. enterocoliticaY. enterocolitica exists in >50 exists in >50 serotypesserotypes

Most isolates from human Most isolates from human disease belong to serotypes O3, disease belong to serotypes O3, O8 and O9O8 and O9

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There are striking geographic There are striking geographic differences in the distribution of differences in the distribution of Y. enterocolitica Y. enterocolitica serotypesserotypes

Y. pseudotuberculosis Y. pseudotuberculosis exists in at exists in at least six serotypes, but least six serotypes, but serotypes O1 accounts for most serotypes O1 accounts for most human infectionshuman infections

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Y. enterocoliticaY. enterocolitica can produce a can produce a heat-stable enterotoxin but the role heat-stable enterotoxin but the role of toxin in diarrhoea associated of toxin in diarrhoea associated infection is not well definedinfection is not well defined

Y. enterocolitica Y. enterocolitica has been isolated has been isolated from rodents and domestic animals from rodents and domestic animals and water contaminated by themand water contaminated by them

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Transmission to humans occurs by Transmission to humans occurs by contamination of food, drink or fomitescontamination of food, drink or fomites

Y. pseudotuberculosis Y. pseudotuberculosis occurs in domestic occurs in domestic and farm animals and birds which excrete and farm animals and birds which excrete the organisms in fecesthe organisms in feces

Human infection probably results from Human infection probably results from ingestion of materials contaminated with ingestion of materials contaminated with animal fecesanimal feces

Person to person transmission with either Person to person transmission with either of these organisms is probably rareof these organisms is probably rare

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Pathogenesis and Clinical FindingsPathogenesis and Clinical Findings An inoculum of 10An inoculum of 1088 – 10 – 1099 yersiniae yersiniae

must enter the alimentary tract to must enter the alimentary tract to produce infectionproduce infection

During IP of 5 – 10 days, yersiniae During IP of 5 – 10 days, yersiniae multiply in the gut mucosa multiply in the gut mucosa particularly the ileum particularly the ileum

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Leads to inflammation and ulceration Leads to inflammation and ulceration and leukocytes appear in fecesand leukocytes appear in feces

The process may extend to mesenteric The process may extend to mesenteric lymph nodes and rarely to bacteremialymph nodes and rarely to bacteremia

Early symptoms include fever, Early symptoms include fever, abdominal pain, and diarrhoeaabdominal pain, and diarrhoea

Diarrhoea ranges from watery to bloody Diarrhoea ranges from watery to bloody and may be due to an enterotoxin or to and may be due to an enterotoxin or to invasion of the mucosainvasion of the mucosa

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At times abdominal pain is severe and At times abdominal pain is severe and located in the right lower quadrant located in the right lower quadrant suggesting appendicitissuggesting appendicitis

1 to 2 weeks after onset some pts develop 1 to 2 weeks after onset some pts develop arthalgia, arthritis and erythema nodosum arthalgia, arthritis and erythema nodosum suggesting immunologic reaction to the suggesting immunologic reaction to the infectioninfection

Very rarely, it produces pneumonia, Very rarely, it produces pneumonia, meningitis or sepsis; in most cases, it is meningitis or sepsis; in most cases, it is self-limitedself-limited

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Diagnostic Lab TestsDiagnostic Lab Tests

SpecimensSpecimens Stool, blood, or material obtained at Stool, blood, or material obtained at

surgical explorationsurgical exploration

CultureCulture No. in stool may be small and can be No. in stool may be small and can be

increased by cold enrichmentincreased by cold enrichment

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A small amount of feces or a rectal A small amount of feces or a rectal swab is placed in buffered saline, pH swab is placed in buffered saline, pH 7.6, and kept at 4 7.6, and kept at 4 C for 2-4 weeks; C for 2-4 weeks; many fecal organisms do not survive many fecal organisms do not survive but but Y. enterocoliticaY. enterocolitica will multiply will multiply

Subcultures made at intervals on Subcultures made at intervals on MCA may yield yersiniaeMCA may yield yersiniae

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SerologySerology In paired serum specimens taken 2 In paired serum specimens taken 2

or more weeks apart, a rise in or more weeks apart, a rise in agglutinating antibodies can be agglutinating antibodies can be shownshown

However, cross reactions between However, cross reactions between yersiniae and other organisms such yersiniae and other organisms such as vibrios, salmonellae, brucellae as vibrios, salmonellae, brucellae may confuse the results may confuse the results

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TreatmentTreatment Most yersinia infections with diarrhoea Most yersinia infections with diarrhoea

are self-limitedare self-limited Y. enterocolitica Y. enterocolitica is generally susceptible is generally susceptible

to aminoglycosides, chloramphenicol, to aminoglycosides, chloramphenicol, tetracycline, trimethoprim-tetracycline, trimethoprim-sulphamethoxazole,piperacillin, 3sulphamethoxazole,piperacillin, 3rdrd generation cephalosporins and generation cephalosporins and fluoroquinolonesfluoroquinolones

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Typically resistant to ampicillin and 1Typically resistant to ampicillin and 1stst generation cephalosporinsgeneration cephalosporins

Proved yersinia sepsis or meningitis has a Proved yersinia sepsis or meningitis has a high mortality rate but deaths occur high mortality rate but deaths occur mainly in immunocompromised patientsmainly in immunocompromised patients

Yersinia sepsis can be successfully treated Yersinia sepsis can be successfully treated with 3with 3rdrd generation cephalosporins generation cephalosporins possibly in combination with possibly in combination with aminoglycosides or a fluoroquinolone aminoglycosides or a fluoroquinolone possibly with another antimicrobial possibly with another antimicrobial

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Prevention and ControlPrevention and Control Contact with farm and domestic animals, Contact with farm and domestic animals,

their feces or materials contaminated by their feces or materials contaminated by them probably accounts for most human them probably accounts for most human infectionsinfections

Meat and dairy products have occasionally Meat and dairy products have occasionally been indicated as sources of infection, and been indicated as sources of infection, and group outbreaks have been traced to group outbreaks have been traced to contaminated food or drinkcontaminated food or drink

Conventional sanitary precautions are Conventional sanitary precautions are probably helpfulprobably helpful

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PasteurellaPasteurella

Species are primarily animal Species are primarily animal pathogens but can produce a range pathogens but can produce a range of human diseasesof human diseases

Pasteurella formerly included all Pasteurella formerly included all yersiniae and francisellaeyersiniae and francisellae

Are nonmotile gram negative Are nonmotile gram negative coccobacilli with a bipolar coccobacilli with a bipolar appearance on stained smearsappearance on stained smears

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Are aerobes or facultative anaerobes Are aerobes or facultative anaerobes that grow readily on ordinary that grow readily on ordinary bacteriologic media at 37 bacteriologic media at 37 CC

Are all oxidase positive and catalase Are all oxidase positive and catalase positive but diverge in other positive but diverge in other biochemical reactionsbiochemical reactions

P. multocidaP. multocida occurs worldwide in the occurs worldwide in the respiratory and GI tracts of many respiratory and GI tracts of many domestic and wild animalsdomestic and wild animals

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Perhaps most common organism in human Perhaps most common organism in human wounds inflicted by bites from cats and wounds inflicted by bites from cats and dogsdogs

One of the common causes of hemorrhagic One of the common causes of hemorrhagic septicaemia in a variety of animals septicaemia in a variety of animals including rabbits, rats, horses, sheep, fowl, including rabbits, rats, horses, sheep, fowl, cats and swinecats and swine

Can also produce human infections in Can also produce human infections in many systems and may at times be part of many systems and may at times be part of normal human floranormal human flora

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P. haemolyticaP. haemolytica occurs in the URT of occurs in the URT of cattle, sheep, swine, horses and fowlcattle, sheep, swine, horses and fowl

Prominent cause of epizootic Prominent cause of epizootic pneumonia in cattle and sheep and pneumonia in cattle and sheep and of fowl cholera in chickens and of fowl cholera in chickens and turkeys causing major economic turkeys causing major economic losseslosses

Human infection appears to be rareHuman infection appears to be rare

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PasteurellaPasteurella P. pneumotropicaP. pneumotropica is a normal inhabitant is a normal inhabitant

of the RT and gut of mice and ratsof the RT and gut of mice and rats Can cause pneumonia or sepsis when Can cause pneumonia or sepsis when

the host-parasite balance is disturbedthe host-parasite balance is disturbed A few human infections have followed A few human infections have followed

animal bitesanimal bites P. ureaeP. ureae has rarely been found in has rarely been found in

animals but occurs as part of a mixed animals but occurs as part of a mixed flora in human chronic respiratory flora in human chronic respiratory disease or other suppurative infections disease or other suppurative infections

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Most common presentation is a history of Most common presentation is a history of animal bite followed within hrs by an acute animal bite followed within hrs by an acute onset of redness, swelling and painonset of redness, swelling and pain

Regional lymphadenopathy is variable and Regional lymphadenopathy is variable and fever is often low gradefever is often low grade

Infections sometimes present as Infections sometimes present as bacteremia or chronic respiratory infection bacteremia or chronic respiratory infection without an evident connection with without an evident connection with animalsanimals

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P. multocida P. multocida is susceptible to is susceptible to most antibioticsmost antibiotics

Pen G is considered the drug of Pen G is considered the drug of choice for choice for P. multocidaP. multocida infections infections resulting from animal bitesresulting from animal bites

Tetracycline and Tetracycline and fluoroquinolones are alternative fluoroquinolones are alternative drugsdrugs

Technology

Yersinia 2007