brucella & yersinia

8/17/2019 Brucella & Yersinia

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Brucella

• The genus Brucella consists of six species,

four of which cause human brucellosis 布

鲁菌病： Brucella melitensis 羊布鲁菌 ,

Brucella suis 猪布鲁菌 , Brucella abortus

牛布鲁菌 , and Brucella canis 犬布鲁菌

• Are all intracellular organisms

• B. neotomae; B. ovis


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• Brucella are small (0.4～

0.8 0.5～ 1.5 m), non-motile, non-capasulate,

gram-negative coccobacilli.

• The organism is aerobic,

and their nutritionalreuirements are comple!.

• "ll strains gro# best in a

medium enrich #ith animalserum and glucose

• 5-10$ carbon dio!ide


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Antigenic Structure and

classification• Two main antigen: A and M

• The three main Brucella differ from one another

in the amount or the two main antigen they have

in common :

Babortus : A:M!"#:$

Bmelitensis: A:M!$:"#

Bsuis: A:M!":$


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B. abortus

• Bacteria is e!creted in genital secretions(including semen), mil%, colostrum.

• &urvival time:

%heese at &o%: $'# days (((

)ater at "*o%: *# days

Meat and salted meat: +* days

Manure at $"o%: "*# days ((((

• 'idespread %attle, Bison, l-, .eer, Moose, /orse,Sheep, 0oat, Swine, .on-ey, .ogs, Birds, /ares, 1ox, 2ats,

mice, %amels and /uman


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B. abortus

• &ources o *uman +nection

2aw mil- and products 3.irect contact• ortal o entr: oral mucosa, nasopharynx and

con4unctivae, genital then in regional lymphnode and spread to 2S 5nodes of udder, uterus,erythritol6 7lacentitis with endometritis 1etusdie with edema 3congestion of lung, dissimenatedhemorrhages of epicardium and splenic capsuleBacteria in lung and digestive tract of the fetus

B. abortus

• Bacteria is e!creted in genital secretions

(including semen), mil%, colostrum.

• &urvival time:

%heese at &o%: $'# days (((

)ater at "*o%: *# days

Meat and salted meat: +* days

Manure at $"o%: "*# days ((((

• 'idespread %attle, Bison, l-, .eer, Moose, /orse,Sheep, 0oat, Swine, .on-ey, .ogs, Birds, /ares, 1ox, 2ats,

mice, %amels and /uman

B. melitensis

• /oat (188), &heep,o# (1205 in

3alta), ine,

*ares, amels,

Bualo, +mpala

B. suis• 'ild pigs, ats, ine.

• "bortion,metritis,

bursitis, spondlitis

(umbar and sacral),

arthritis, orchitis,paralsis.

Brucella canis

• Brucella canis was first described as a cause ofabortion in beagles in the 8SA

• 9t was subseuently shown to infect dogs in many

other countries, irrespective of breed• An occasional cause of brucellosis in humans


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Spread of Brucella in the body


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9ncubation period

• Acute or subacute disease follows an incubation period which can vary from 1 #ee% to or moremonths

• 9n most patients for whom the time of exposure

can be identified, the incubation period is between6 and #ee%s

• The length of the incubation period may beinfluenced by many factors

; virulence of the infecting strain ; si


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ortals o entr

• 7ral entr - most common route

; 9ngestion of contaminated animal products

5often raw mil- or its derivatives6

; contact with contaminated fingers

• "erosols

; 9nhalation of bacteria

; %ontamination of the con4unctivae

• ercutaneous infection through s-in

abrasions or by accidental inoculation


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linical 3aniestations

• The presentation of brucellosis is characteristicallyvariable

• The onset may be insidious or abrupt• +nluena-li%e with fever reaching =' to o%

; imb and bac% pains are unusually severe,

night s#eating and fatigue are mar-ed ; Anorexia, wea-ness, severe fatigue and loss of

weight, depression ; *eadache

• The leu-ocyte count tends to be normal or reduced,with a relative lmphoctosis ; 2elative leu-openia

• >n physical examination, splenomegal may be the

only finding


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79&: 7; B9:7&+&

• 9f the disease is not treated, the symptomsmay continue for 6 to 4 #ee%s

; Many patients will then recover spontaneousl

; >thers may suffer a series of e!acerbations

• May produce an undulant ever inwhich the intensity of fever and

symptoms recur and recede at about $#day intervals


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Brucellosis

• prus ever


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73+"T+7?&

• Arthritis, often sacroiliitis, and spondlitis

5in about $# percent of cases6

• central nervous system involvement including

meningitis 5in about *@6

• 8veitis, epididymo?orchitis

• ndocarditis very rare• +n contrast to animals, abortion is not a

eature o brucellosis in pregnant #omen.


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A20 >9CTS


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S7>C.D9T9S脊椎炎


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SA%2>999T9S 骶髂关节炎


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hronic Brucellosis- @epression


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7opulation ris-

• The main source of infection for the general population is dair produce prepared from infectedmil-

• B. melitensis presents the greatest ha


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>ccupational ha


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:!tending spectrum o oonosis

• The recent isolation of distinctive Brucella strains,tentatively named Brucella maris, from marineanimals in the 8nited Eingdom and the 8nitedStates extends the ecologic range of the genus and, potentially, its scope as a


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%9C9%A .9A0C>S9S


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&anitar

• 7asteuri


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7revention• radication of brucellosis in cattle can be attempted by

test and slaughter,active immuni


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Treatment• Brucella may be susceptible to tetracyclines or

ampicillin

•Symptomatic relief may occur within a few days aftertreatment with these drugs is begun

• /owever ,because of their intracellular location,theorganisms are not readily eradicated completely fromthe host

• 1or best results,treatment must be prolonged%ombinedtreatment with streptomycin and a tetracycline may beconsidered


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D2S9C9A


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0enus Dersinia• D pestis

• D enterocolitica

• D pseudotuberculosis

:nterobacteriaceae

0enus scherichia

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Biological 1eatures

; Small, #*?#' Gm in width

$#?"# Gm in length ; 0ram?negative rods

; Sometimes appearing as

cocco bacilli ; Bipolar Staining:2etaining

stain at the ends of cells


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Biological 1eatures

• %ultural 1eatures ; 1acultative anaerobes

; >ptimal growth temperature range form "'H%to =#H%

; >ptimal growth p/: +F～ I"

; 0rowth is more rapid in media containing blood or tissue fluids

; Conmotile when grow at temperatures above =#H%


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7athogenicity

Transmission:

1lea2espiratory Tract

Bite


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Antigenic Structure

• 1$ Antigen:

• J,) Antigen:

• Dersinia >uter membrane 7rotein 5Dop6

• Murine Toxin 5MT6

#=@?#&@ formaldehyde Toxoid

• ndotoxin 57S6


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D 7estis Jirulence factors schematic diagram

1$ Antigen1$ 0ene

7lasmid7lasmid

%a"K .ependent

0ene J?) 0ene

) Antigen

J Antigen7S


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7athogenesis

D pestis 7hagocyte

mph ?odes

+n /roin and

"!illa

nter

2espiratory System

9nvade

Pneumonic Plague Bubonic Plague

9nvade Blood Stream

Septicemic Plague meningitis


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7athogenicity

• %linical 1orms :

; Bubonic Plague: /igh fever, Swelling,

Bleeding, Cecrosis of lymph nodes ; Pneumonic Plague: chills, cough, respiratory

failure, circulatory collapse LL Blac- .eath

; Septicemic Plague: 1ever 5=F? H%6 , Shoc- ,.9%


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Dnterocolitica D7seudotuberculosis

• 0ram negative, Co capsule, Co spore, 1acultativeanaerobes

• J－) antigen

• More than *# serotypes of Dnterocolitica

+ serotypes of D7seudotuberculosis

• .iseases: ; 0astroenteritis

; terminal ileitis, appendicitis, mesenteric lymphadenitis,

; dermatitis contusiformia, arthritis

; Septicemia

• Sanitary precautions, Antibiotic


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pidemiology

• 7lague

; 7robably originated in Asia or central Africa ; >ne of the earliest record pandemics occurred

in *&" B%

; Three pandemics in the history

; $F'F－ $FF'： *& cases, +'$ dead


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9mmunity

%ellular

9mmunity

/umoral

9mmunity

$6 1$ Ag "6 J,) Ag 7hagocytose

Antibody To:

7romote phagocytose , agglutinate and -ill bacteria


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.iagnosis• A. Specimens:

; Aspirates of lymph nodes

; %erebrospinal fluid

; Blood

; Sputum

B. Smears:

0iemsaNs stain

immunofluorescent stain


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.iagnosis• C. Culture:

; All materials %ultured on blood agar and

Mac%on-eyNs agar and in infusion broth

; 7ositive in "& hours ; Tentatively identified by biochemical reations

.efinite identified by immunofluorescence

"9T+7?: All cultures are highly infectious and must be

handled with extreme caution


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.iagnosis

• . Serology:

9n patients who have not been previously

vaccinated, a convalescent serum antibodytiter of $:$+ or greater is presumptive

evidence of Dpestis infectionA titer rise in

two seuential specimens confirms the

serologic diagnosis


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Treatment

• Streptomycin

• Tetracycline:

alternative drug

combination with streptomycin

essential for control early in disease

• Sulfonamides


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Summary of Yersinia infections


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Bacillus


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Spore?1orming 0ram?7ositive Bacilli:


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Bacillus Species

• At least &' species are -nown but only• B. anthracis and B. cereus cause defined

diseases in humans

• B. anthracis is responsible for the disease anthrax• This is a disease primaril o animals (oonosis6 but humans can

acuire via handling, inhaling or ingesting contaminated animal products

• B. cereus is predominantly responsible for food poisoning in humans

• Bacitracin and polm!in are two well?-nownantibiotics obtained from Bacillus species

• &pores o man Bacillus species are resistant to heat, radiation, disinectantsand desiccation


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• 9t was from studies on anthrax that Eoch

established his famous postulates in $'I+• 7asteur 5$''$6 developed a vaccine against

anthrax


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B. anthracis Gram stain

demonstrating spores

B th i


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B. anthracis,

%olony on SBA

OS % P % i f


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OST9%EDP %onsistency of

B. anthracis’ %olony on SBA


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Anthrax infections are classified

by route of entry

• utaneous

• /astrointestinal

• espirator


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utaneous "nthra!

• A 25$ o naturall occurring casesA 25$ o naturall occurring cases

•

&pores enter brea%s in s%in ater contact #ith&pores enter brea%s in s%in ater contact #ithcontaminated animal productscontaminated animal products

• apuleapule丘疹 - esicle- esicle水泡 - 9lcer - :schar- 9lcer - :schar焦

痂

• 9p to 60$ case atalit rate i untreated9p to 60$ case atalit rate i untreated

• 3ortalit #ith treatment C 1$3ortalit #ith treatment C 1$


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• After a 2- to 3-day incubation period, a smallpimple or papule appears at the inoculationsite.

• A surrounding ring of vesicles develops

Over the next few days, the central papule

ulcerates, dries, and blackens to form the

eschar


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Jesicles Blac- schar

i l d


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7ainless dema

• The lesion is painless and is surrounded by mar%ed edema that

may extend for some distance• 7us and pain appear only if the lesion becomes inected b a

pogenic organism

• Similarly, mar%ed lmphangitis淋巴管炎 and ever usually

point to a secondary infection

l ti f th h i


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volution of an anthrax eschar in

a &?year?old boy

.AD +


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.AD $# ? $*


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•


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Evolution of an anthrax eschar in a 4-year-old boy.(A&B) the lesion when first seen (day 0).Note the arm swollen from the characteristic

edema.

(C) Day 6. (D) Day 10. (E) Day 15.

Altho!h "enicillin treatment was #e!n immediately and the lesion was sterile #y

a#ot $% hors

it contined to e'ol'e and resol'e as seen.


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%utaneous anthrax

.ifferential diagnosiscthyma gangrenosum

2at?bite fever

8lceroglandular tularemia7lague

0landers

2ic-ettsialpox

>rf

Staphylococcal lymphadenitis%utaneous tuberculosis

eprosy

Buruli ulcer

Pseudomonas aeruinosa

Streptobacillus monili!ormis,

Spirillum minor

"rancisella tularensisYersinia pestis

Pseudomonas pseudomallei

#ic$ettsia a$ari

7arapoxvirus

Staph%lococcus aureus &%ocbacterium tuberculosis

&%cobacterium leprae

&%cobacterium ulcerans


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%utaneous anthrax

•

For cutaneous and gastrointestinanthrax, low-level germinationoccurs at the primary site, leading

to local edema and necrosis


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+nhalation

• Bacillus spores are inhaled and ingested by alveolar macrophages肺泡巨!"

• These cells carry the bacteria to theregional lmph nodes, causing necrotic

hemorrhaging which leads to death


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/astrointestinal

• 9ngestion of contaminated meat producessystemic symptoms which can lead to death

• Mortality by gastrointestinal anthrax may

be *#@


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0astrointestinal and pulmonary

anthrax are both more dangerousthan the cutaneous orm

because they are usually

identiied too late for treatmentto be effective

PA!"#$%$&'&


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PA!"#$%$&'&

•Anthrax infections result only if the bacteria produce a ; i6 capsule 5poly?y?.?glutamic acid polypeptide6

; ii6 e!oto!ins

; both encoded on plasmids

• three proteins

• protective antigen 57A6 5'" I -.a6

• lethal factor 516 5F#" -.a6

• edema factor 516 5''F -.a6

ANTHRAX TOXIN

ANTHRAX TOXIN


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ANTHRAX TOXINANTHRAX TOXIN

!"

E"

#A

#A

#A

!"

Host

#rotease

HOT $E!!

60%&a

The comple! ("D; or

"D:;) is internalied b

endoctosis

acidiication o the endosome

the ; or :; cross the

membrane into the ctosol via

"-mediated ion-conductive

channels


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Efects o anthrax

exotoxins on macrophages• $dema toxin is acalmodulin#$节%& -dependent adenylatecyclase that increasesintracellular levels ocyclic AMP (cAMP) onentry into most typeso cell

• This is elieved to

alter waterhomeostasis! resulting in massive

edema


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Efects o anthrax

exotoxins on macrophages• (ethal toxin is a "inc

metallo-protease thatcauses a hyperin#ammatorycondition in macrophages

! activating the oxidativeurst path$ay

• release o reactiveoxygen intermediates

! production oproin#ammatory cyto%ines

• responsible for shoc)and death&

• MAP'' denotes mitogen-activated protein %inase%inase


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•$ndosporesare

phagocytosed bymacrophages and

germinate•*acrophages containingbacilli

detach and


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•egetative anthrax acilli gro$ in the lymph nodecreating regional hemorrhagic lymphadenitis•*acteria spread through the lood and lymph andincrease to high numers causing severe septicemia•+igh levels o exotoxins are produced that areres onsile or overt s m toms and death&


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•,n a small numer o cases systemic anthrax can lead tomeningeal involvement y means o lymphatic orhematogenous spread•,n pulmonary anthrax perironchial hemorrhagiclymphadenitis loc%s pulmonary lymphatic drainage

• leadin to ulmonar edema


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nce they have een released rom themacrophages there is no evidencethat an immune response is initiatedagainst vegetative bacilli


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rotective immunit

• Antibodies against protective antigen

• Both the noncellular human vaccines andlive?spore animal vaccines confer protection

by eliciting antibodies to protective antigen• The poly?g?.?glutamic acid capsule of B

anthracis is poorly immunogenic, and

antibodies to the polysaccharide and othercomponents of the cell wall are not protective


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&pecies dierences

• Anthrax has been documented in a widevariety of #arm-blooded animals

• Some species, such as rats, chic-ens, and

dogs, are uite resistant to the disease• >thers 5notably herbivores such as cattle,

sheep, and horses6 are very susceptible

• *umans have intermediate susceptibility

reservoir o B anthracis isreservoir o B anthracis is


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reservoir o B anthracis isreservoir o B anthracis is

contaminated soil• &pores remain viable for long periods

• *erbivores, the primary hosts, become infected

when foraging in a contaminated region

• Because the organism does not depend on an

animal reservoir, it cannot readily be eradicated

from a region

; anthra! remains endemic in man countries• *umans become infected almost exclusively

through contact #ith inected animals or animal

products


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cle o inection in nature

• As a susceptible animal with anthrax approaches death, itsblood contains as man as 102 bacilli


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*andling o carcasses'()*

• Sporulation of B anthracis reuires oxygen

; therefore does not occur inside a closed carcass

; regulations in most countries orbidpostmortem e!amination o animals when

anthrax is suspected

; The vegetative cells in the carcass are %illed in a few days by the process of putrefaction


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• 9n endemic areas, animals that die suddenly should

be handled cautiously

• ivestoc- should be vaccinated annually

@o + loo%

that + am going

to dieE


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?on-+ndustrial vs +ndustrial

"nthra!• ?onindustrial anthra!

• usually affects people who wor- with animals or animal

carcasses

; farmers, veterinarians, butchers

; almost always cutaneous

• +ndustrial anthra!

• acuired from handling contaminated hair, hides, wool, bone meal, or other animal products

; higher chance of being pulmonary as a result of the inhalation o

spore-laden dust


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Transmission linical sndrome 'ho is at ris%


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utaneousanthra!

9n4ured s-in or mucousmembranes inoculated byspores from the soil or a

contaminated animal orcarcass

S-in infection begins as araised itchy bump and within$?" days develops into a

vesicle and then a painlessulcer, usually $?= cm indiameter, with acharacteristic blac- necroticarea in the center ymphglands in the ad4acent areamay swell

7eople in endemic areas incontact with infectedanimals of contaminated

soilsQ people who wor-with animals materials5hides, fur, wool, hair6imported from endemicarea, such as farmers,veterinarians, -nac-ers, butchers and

laboratorians+ntestinalanthra!

The ingestion of poorlycoo-ed meat or mil- frominfected animals

9nitial signs of nausea, loss ofappetite, vomiting, and feverare followed by abdominal pain,

vomiting of blood, andsevere diarrhea

ulmonaranthra!

9nhalation of spore?containing dust whereanimal hair or hides are being handled

begins abruptly with highfever and chest pain, progresses rapidly to asystemic hemorrhagic pathology


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Bacillus ereus+,-".菌

• B. cereus ood poisoning results rom the

ingestion o preormed enteroto!ins, producing

predominantl vomiting and diarrhea.

• The vomiting orm is most oten associated

#ith ingestion o a heat stable to!in rom

contaminated rice, #hile the diarrheal orm is

most oten associated #ith ingestion o a heatlabile to!in rom contaminated meat or

vegetables


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B cereus virulence actors

• A =' to &+?-.a protein comple! has been shown in animal models:

; to cause necrosis of the s-in or intestinal mucosa

; to induce fluid accumulation in the intestine

; a lethal toxin• 2esponsible for the necrotic and toxemic nature of severe B cereus

infections and for the diarrheal form of food poisoning

Bacillus cereus also produces t#o hemolsins

hospholipases produced b B cereus ma act as e!acerbating

actors

b degrading host cell membranes ollo#ing e!posure o their

phospholipid substrates in #ounds or other inections


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T#o @istinct Tpes• @iarrheal tpe

• diarrhea and abdominal pain

• 8 to 1 hours after consumption of the contaminated food

• Associated with a variety of foods, including meat andvegetable dishes, sauces, pastas, desserts, and dairy

products

• :metic/0 disease• nausea and vomiting begin 1 to 5 hours after the

contaminated food is eaten

• Boiled rice that is held for prolonged periods at ambienttemperature and then uic%-ried beore serving is theusual offender although dairy products or other foods are

brucella & yersinia

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