1 קמפילובקטר campylobacter c. fetus veneralis c. fetus fetus c. jejuni c. coli c....

1

קמפילובקטרCampylobacter

C. fetus veneralis

C. fetus fetus

C. jejuni

C. coli

C. upsaliensis

C. lari

C. hyointestinalis

2

קמפילובקטרCampylobacter

Animal host Animal disease Human disease

C. fetus venerealis cattle Abortion infertility None reported

C. fetus fetus cattle sheep goats abortion Bacteremia diarrhea abortion

C. jejuni Poultry ruminants dogs cats humans

Abortion diarr asymptomatic

Bacteremia diar

C. coli Pigs poultry sheep Asymp abortion Bacteremia diar

C. upsaliensis Dogs cats poultry Asymp diarrhea Bacteremia diar

C. lari Wild birds dogs None reported Bacteremia diar

C. hyointestinalis Poultry cattle sheep dogs cats pigs pets

None reported Bacteremia diar

3

תכונות:

בעלי תנועה )שוטון אחד(•מרביתם מיקרואורפיליים •vibriosis לכן השם vibrio)בעבר השתייכו לקב' •אינם מפרקים סוכרים אלא מנצלים תוצרי ביניים של •

לשם מקור אנרגיה.TCAמעגל ה

מתגים דקים, מעוגלים, צורת פסיק, "שחף".•

4

:תרביתדרושים מצעים מיוחדים )תוספת אנטיביוטיקה •

+ פירובט )כנגד רדיקלים של חמצן( ו%- גבוה של חנקןCO2 10% חמצן, 5%• שעות ויותר(48צמיחה איטית )•

דרוש מצע הובלה מיוחדק. ונירליס ל•

5

אנטיגנים משמשים Heat labile + O antigens ק. ג'גוני:•

לחלוקה לקבוצות סרולוגיות.

תת קבוצות ע"י אנטיגן פלגילרי.•

6

אנטיגנים שכבה חיצונית של המעטפת העשויה חלבונים חומציים והידרופוביים בעלי S-layer (surface array proteins)–SAPק. פטוס: •

משקל מולקולרי גבוה.

שינויים במבנה הדו-מימדי של חלבונים אלו קובעים את האימונוגניות ואת החלוקה לתת-קבוצות סרולוגיות ביחד עם אנטיגן • של חיידקים אלו.LPS של ה-Oה-

Campylobacter jejuni: molecular biology and pathogenesis , Kathryn T. Young, Lindsay M. Campylobacter jejuni: molecular biology and pathogenesis , Kathryn T. Young, Lindsay M. Davis & Victor J. DiRita, Nature Reviews Microbiology 5, 665-679 (September 2007)Davis & Victor J. DiRita, Nature Reviews Microbiology 5, 665-679 (September 2007)

7

אנטיגנים• the S-layer confers resistance to complement mediated killing in non-immune

serum by preventing the binding of complement factor C3b to the C. fetus cell surface.

• S-layer expressing C. fetus strains remain susceptible to complement independent killing, utilizing opsonic antibodies directed against the S-layer.

8

גורמי אלימות:

• Motility and chemotaxis (flagella etc)– Chemoattraction towards bile and mucin allows

colonization of the intestine and gall bladder

• adherence to epithelial cells– Adherence with proteins, flagella and

lipopolysaccharide.– Campylobacter are adherent to cell membrane

and are internalized into cytoplasmic vacuoles. – flagellin and adhesion both are required for

irreversible binding of bacteria to cells

9The clinical importance of emerging Campylobacter species, Si Ming Man, Nature Reviews Gastroenterology & Hepatology 8, 669-685 (2011The clinical importance of emerging Campylobacter species, Si Ming Man, Nature Reviews Gastroenterology & Hepatology 8, 669-685 (2011 ))

• Mucosa-associated bacteria have the capacity to swim through the mucus layer that covers the Mucosa-associated bacteria have the capacity to swim through the mucus layer that covers the intestinal epithelium.intestinal epithelium.

• Attach to and invade intestinal epithelial cells (C. coli, C. concisus, C. fetus, C. rectus and C. Attach to and invade intestinal epithelial cells (C. coli, C. concisus, C. fetus, C. rectus and C. upsaliensis)upsaliensis)


• Translocate across the intestinal epithelium either via a transcellular route (C. Translocate across the intestinal epithelium either via a transcellular route (C. fetus) and/or via a paracellular route by breaking down barrier-associated tight fetus) and/or via a paracellular route by breaking down barrier-associated tight junctions (C. concisus).junctions (C. concisus).

11

גורמי אלימות:

• Intracellular :– C. fetus is capable of adhering, entering, and

surviving within the nonphagocytic epithelial cells

• Proteins and enzymes– cytolethal distending toxin (CDT) causes cellular

distention and eventually death of the cell lines – hemolysin. – Catalase is required for Campylobacter hydrogen

peroxide resistance as well as persistence in macrophages


• Deliver effector proteins into host epithelial cells via a putative Deliver effector proteins into host epithelial cells via a putative T4SS (C. fetus, C. coli).T4SS (C. fetus, C. coli).


• The S-layer mediates resistance to phagocytosis and serum-killing (C. fetus, C. rectus), The S-layer mediates resistance to phagocytosis and serum-killing (C. fetus, C. rectus), possibly by inhibiting stable complement deposition onto bacterial cell surface during the possibly by inhibiting stable complement deposition onto bacterial cell surface during the

systemic phase of infectionsystemic phase of infection. .


• generate a number of toxins, including the tripartite (CDT) cytolethal distending toxin (C. generate a number of toxins, including the tripartite (CDT) cytolethal distending toxin (C. coli, C. fetus, C. hyointestinalis, C. lari and C. upsaliensis). Binding of this toxin to the host coli, C. fetus, C. hyointestinalis, C. lari and C. upsaliensis). Binding of this toxin to the host cell surface is mediated by CdtA and CdtC, followed by delivery of CdtB into the host cell surface is mediated by CdtA and CdtC, followed by delivery of CdtB into the host

nucleus, which initiates cell cycle arrest and DNA damagenucleus, which initiates cell cycle arrest and DNA damage ..


Other toxins include cell-bound and secreted hemolysins, which have Other toxins include cell-bound and secreted hemolysins, which have the capacity to lyse red blood cells (C. coli and C. concisus)the capacity to lyse red blood cells (C. coli and C. concisus) . .

16

Cell Wall• typical of gram-negative cells. • three layers,

– an outer lipoprotein layer, – a middle lipopolysaccharide layer – inner mucopeptide layer.

• The LPS consisted of three distinct regions– lipid A anchored in the outer membrane and is the endotoxic part of

the LPS molecule. – the core, which is attached to the lipid– the O antigen attached to the outer core.

• The LPS molecules of Campylobacter are involved in adherence and play a role in antigenic variations, as Campylobacter has the ability to shift the LPS antigenic composition.

• Surprisingly N-acetyl neuraminic acid (sialic acid) is present in the core oligosaccharide, not frequently found in prokaryotes. These sialic acid residues appeared like gangliosides in structure, when attached to –D galactosidase.

• This molecular mimicry is involved in the neuropathological autoimmune diseases like Guillains Barre' Syndrome and Reiter syndrome.

17

סביבת חיים•C. f. veneralis הינו טפיל אובלגטורי של העורלה

בפרים ומע' המין בפרות נגועות )בתוך חללי הבושת, צוואר הרחם, הרחם והחצוצרות( .

•C.fetus fetus מגיע לרחם בצאן דרך מע' העיכול ולאחר איכלוס הרקמות העובריות, גורם למות

העובר והפלה.

של מע' העיכול commensalsמרבית האחרים :•של בבקר, צאן, כלבים, עופות ובעלי חיים אחרים.

18

Survival in the Environment

• Survival of C. jejuni outside the gut is poor, and replication does not occur readily.

• C. jejuni grows best at 37°C to 42°C, the approximate body temperature of the chicken (41°C to 42°C).

• C. jejuni grows best in a low oxygen or microaerophilic environment, such as an atmosphere of 5% O2, 10% CO2, and 85% N2.

• The organism is sensitive to freezing, drying, acidic conditions (pH < 5.0), and salinity.

20

C. jejuni : בבקר, צאן, כלבים

נמצא במע' העיכול ללא סימנים •קליניים.

הפלות ספורדיות.•

דלקת כבד בעופות.•

21

חתולים

לרב ללא סימנים•

יתכן שלשול מימי, רירי עם או בלי דם.•

עופותעופות

צעירים: דלקת מעיים חריפה – שלשול, מוות צעירים: דלקת מעיים חריפה – שלשול, מוות•

בוגרים: לרב ללא סימנים קליניים בוגרים: לרב ללא סימנים קליניים•

22

העברה

מקורות:•צואה, זיהום משני, הפרשות רחם, נפלים, בשר –

עוף, בשר אחר, חלב לא מפוסטר, מים, ירקות מזוהמים, צדפים ועוד.

העברה מכאנית ע"י זבובים–

מצב של נשאות בבע"ח אך בד"כ לא באדם.•

העברה •אורו-פקאלית

23

C. jejuniבבני אדם :

עם פיזור ממע' העיכול יתכנו בקטראמיה, דלקות •פרקים, מע' השתן, קרומי המוח, אנדוקרדיטיס,

קרום הבטן, הפלות, זיהום עוברי.

acute לאחרונה נמצא קשר לתסמונת של •polyneuropathy ע"ש Guillain-Barré.

שלשול, חום, כאבי •בטן חריפים, הקאות

רמת ההדבקה היא • איש.1000/100,000

24

Disease Prevalence• In the United States, an estimated 2.1 to 2.4 million cases of

human campylobacteriosis (illnesses ranging from loose stools to dysentery) occur each year.

• Commonly reported symptoms of patients with laboratory-confirmed infections (a small subset of all cases) include diarrhea, fever, and abdominal cramping.

• In one study, approximately half of the patients with laboratory-confirmed campylobacteriosis reported a history of bloody diarrhea.

• Less frequently, C. jejuni infections produce bacteremia, septic arthritis, and other extraintestinal symptoms.

• Centers for Disease Control and Prevention/U.S. Department of Agriculture/Food and Drug Administration Collaborating Sites Foodborne Disease Active Surveillance Network, 1996

25

Outbreak of Campylobacter jejuni Infections Associated with Drinking Unpasteurized Milk Procured Through a Cow-Leasing Program ―

Wisconsin, 2001 During November and December 2001, seventy-five persons from

Northwestern Wisconsin became ill with Campylobacter jejuni enteritis. This outbreak was associated with drinking unpasteurized milk obtained through a cow-leasing program that was used to circumvent regulations prohibiting the sale of unpasteurized milk in Wisconsin. Consumers paid an initial fee to lease part of a cow. Farm operators then milked the cows and stored the milk from all leased cows together in a bulk tank. Customers either picked up milk at the farm or farm operators had it delivered. To ensure that unpasteurized milk will not be distributed to the public in Wisconsin, state officials are enforcing existing regulations and prohibiting cow-leasing

systems. For more information on Campylobacter visit this CDC website .

26

Telegraph UK More than 160 mountain bikers made sick by sheep droppings

02 Dec 2008

Public health inspectors were called in after the cyclists fell ill with food poisoning after an event in the Welsh countryside . The cyclists tested positive for the bacterium campylobacter – usually caused by uncooked meat and poultry. But following an investigation by health experts, the muddy mountain cycle course was found to be heavily contaminated with sheep droppings. The cyclists are believed to have been affected by eating meals and snacks during the event – without washing their hands first.

"At that point we launched an internet based questionnaire to investigate the outbreak." More than 660 mountain bikers from all over Britain took part in the Builth Wells Mountain Biking Marathon in Powys in July this year. A total of 355 responses were received with 161 cyclists reporting symptoms such as diarrhoea and vomiting.

The report, by the NPHSW, concluded the outbreak was caused by campylobacter spread to the cyclists by mud which was contaminated with sheep faeces. Heavy overnight rain is likely to have contributed to the outbreak by increasing the amount of liquid mud on the course. The report recommended cyclists to eat out of protective wrappers at future events.

27

Sequelae to Infection• Guillain-Barré syndrome (GBS), a demyelating disorder

resulting in acute neuromuscular paralysis, is a serious sequela of Campylobacter infection. An estimated one case of GBS occurs for every 1,000 cases of campylobacteriosis.

• Up to 40% of patients with the syndrome have evidence of recent Campylobacter infection .

• Approximately 20% of patients with GBS are left with some disability, and approximately 5% die despite advances in respiratory care.

Allos BM. Association between Campylobacter infection and Guillain-Barré syndrome. J Infect Dis 1997;176:S125-8.

28

Guillain-Barre syndrome

acute inflammatory demyelinating polyneuropathy (AIDP)

29

GBS Pathogenesis• precise mechanism of GBS is unclear.• certainly has an immunological basis;• most likely an autoimmunity triggered by an

exogenous antigen. • It has been linked epidemiologically to

Campylobacter jejuni as well as other infectious agents.

• The preceding infection creates an immunological response to proteins epitopically similar to myelin.

30

This is a mid-power image of a nerve which has been stained with a different myelin stain, which stains the myelin blue. There is patchy myelin loss within the nerve. You an also see some small round lymphocyte nuclei.

This is the same nerve as that in the image immediately above. This time it is stained with an axonal stain. The black horizontal lines are the axons. Note that the axons are preserved even in areas of myelin loss.

31

Sequelae to Infection Reiter syndrome

• Campylobacteriosis is also associated with Reiter syndrome, a reactive arthropathy. In approximately 1% of patients with campylobacteriosis, the sterile postinfection process occurs 7 to 10 days after onset of diarrhea.

• Multiple joints can be affected, particularly the knee joint. Pain and incapacitation can last for months or become chronic.

• Both GBS and Reiter syndrome are thought to be autoimmune responses stimulated by infection.

• The pathogenesis of GBS and Reiter syndrome is not completely understood.

Peterson MC. Rheumatic manifestations of Campylobacter jejuni and C. fetus infections in adults. Scand J Rheumatol 1994;23:167-70.

32

A survey of Campylobacter in animals.Manser PA, Dalziel RW.,Hyg (Lond). 1985 Aug;95(1):15-21

• A survey of Campylobacter species in the faeces or rectal contents of domestic animals was carried out using direct and enrichment culture methods.

• Campylobacters were isolated from 259 (31%) of 846 faecal specimens.

• The highest isolation rate was found in pigs )66%(; cattle )24%( and sheep )22%(. In pigs all the isolates were C. coli, in sheep and cattle about 75% were C. jejuni.

• Only five isolations of C. fetus subsp. fetus were made, all from cattle. More pigs with diarrhoea had C. coli in their faeces than healthy pigs (77% vs 47%), but such a clear difference in isolation rate between sick and healthy animals was not seen in cattle or sheep.

• The results show that cattle, sheep and pigs constitute a large potential source of campylobacter infection for man.

33

כלבים

בסקרים שונים בארץ ובעולם החיידק נמצא • מכלבים ללא סימנים קליניים.28% עד 1.6%ב

בצעירים או במקרים מיוחדים תתכן תחלואה:•שלשול מימי עם מרה, ריר ויתכן דם–הקאות–חוסר תיאבון–+/- חום–

ימים אך יתכן שלשול לסירוגין 3-7נמשך בד"כ •במשך שבועות

35

Antimicrobial Resistance

• The increasing rate of human infections caused by antimicrobial-resistant strains of C. jejuni makes clinical management of cases of campylobacter more difficult.

• Antimicrobial resistance can prolong illness and compromise treatment of patients with bacteremia.

• The rate of antimicrobial-resistant enteric infections is highest in the developing world, where the use of antimicrobial drugs in humans and animals is relatively unrestricted.

•Piddock LJV. Quinolone resistance and Campylobacter spp. Antimicrob Agents Chemother 1995;36:891-8. •Jacobs-Reitsma WF, Kan CA, Bolder NM. The induction of quinolone resistance in Campylobacter bacteria in broilers by quinolone treatment. In: Campylobacters, helicobacters, and related organisms. Newell DG, Ketley JM, Feldman RA, editors. New York: Plenum Press; 1996. p. 307-11.

36

Antimicrobial Resistance• Experimental evidence demonstrates that fluoroquinolone-

susceptible C. jejuni readily become drug-resistant in chickens when these drugs are administered.

• After flouroquinolone use in poultry was approved in Europe, resistant C. jejuni strains emerged rapidly in humans during the early 1990s.

• Similarly, within 2 years of the 1995 approval of fluoroquinolone use for poultry in the United States, the number of domestically acquired human cases of ciprofloxacin-resistant campylobacteriosis doubled in Minnesota.

Smith KE, Besser JM, Leano F, Bender J, Wicklund J, Johnson B, et al. Fluoroquinolone-resistant Campylobacter isolated from humans and poultry in Minnesota [abstract]. Program of the 1st International Conference on Emerging Infectious Diseases; Atlanta, Georgia; 1998 Mar 7-10. Atlanta: Centers for Disease Control and Prevention;1998.

37

Campylobacter fetus subsp veneralis

פרמגע מיני פרה

Campylobacter fetus subsp fetus

צאן צאן

זיהום סביבתי

שליות, נפלים, הפרשו

ת

מעבר אוראל

י

אדם דרך השליה?אדם

מזון מזוהם

?

מגע ישיר?

38

C. fetus veneralis

חדירה למע' המין בעת הרבעה בזמן שיש כמות גדולה של •

נאוטרופילים בהפרשות הווגינליות. לאחר התחמקות

מפאגוציטוזה, ישנה התרבות בריר וחדירה לרחם בשלב

הלוטיאלי

cranial vagina, cervix, uterus and oviducts

subacute endometritis with periglandular lymphocytic infiltration

39

C. fetus veneralis

בבושת המונעים IgA ברחם ו- IgGיצירה של •

חדירה לעומק הרקמה. ) מצב של נשא(

אין גירוי טוב של מע' החיסון ההומורלי.•

ההפלה נחשבת כתוצאה מתגובה אלרגית •

אנדוטוקסינים יציבי חום.

40

תסמונת קלינית

מחלה תת - קלינית: לרוב לא מזוהה מחלה תת - קלינית: לרוב לא מזוהה •

בעיה בפוריות בעיה בפוריות •

חזרה לדרישה - תמותת העובר חזרה לדרישה - תמותת העובר •

( ( 10%10%מעט הפלות )בד"כ פחות ממעט הפלות )בד"כ פחות מ•

הדבקה דרך מערכת המין בלבד.הדבקה דרך מערכת המין בלבד.•

41

C. f. fetusC. f. fetus

הדבקה פקו- אורליהדבקה פקו- אורלי•

בד"כ נמצא במערכת העיכול בלבד בד"כ נמצא במערכת העיכול בלבד •

כבדכבדהמרההמרהשלפוחיתשלפוחית מעיים מעיים •

הריוןהריוןבקטראמיהבקטראמיהרחםרחםשליהשליהדלדל

לעוברלעוברנקרוזהנקרוזהשליהשליהקתקת

42

•Campylobacter fetus subsp veneralis– Few cases documented in man– Debilitating factors )pregnancy, alcoholism,

neoplasia, cardiac dis.

• Campylobacter fetus subsp fetus– Septicemia– 17% - 43% die– Abortion, premature birth, full term birth which

up to 50% may die of meningoencephalitis

Campylobacter fetus in man

43

איבחון מעבדתיאיבחון מעבדתי

בידוד בתרבית + זיהוי.בידוד בתרבית + זיהוי.•הבדלה בין הסוגים ע"י בדיקות ביוכימיות, רגישות –

42 או 25לחומצה נלדיקסית או צפלוטין, וצמיחה ב מעלות.

•Phase contrast microscopyPhase contrast microscopy

אימונופלואורסנציהאימונופלואורסנציה•

מבחן סרולוגי - הצמדה- לא אמיןמבחן סרולוגי - הצמדה- לא אמין•

•PCRPCR

44

מניעה וטיפול

הזרעה מלאכותית + בדיקת הזרעה מלאכותית + בדיקת ק. ונרליס: ק. ונרליס: •הפרים.הפרים.

אנטיביוטיקה בתוך נוזל המשמר של אנטיביוטיקה בתוך נוזל המשמר של •הזירמה.הזירמה.

טיפול: בדר'כ אוקסטטראציקליןטיפול: בדר'כ אוקסטטראציקלין•

חיסון- מומת + אדג'ובנטחיסון- מומת + אדג'ובנט•

45

::ק. פטוס פטוסק. פטוס פטוס

ממשק – נקיון•

טיפול: אוקסטטראציקלין, טילוזין•

חיסון – בקרוב בארץ•גזע תרכיב מתאים לגזעים מקומיים?–

46

ק. ג'גוני:ק. ג'גוני:

בד"כ אין צורך בטיפול.•

מקרים קליניים בכלבים – אנטיביוטיקה •וביקורת במידה וחשש להעברה לבני

אדם.

לבני אדם ישנו חיסון אורלי שבקרוב יצא •לשוק.

47

Control of Campylobacter Infection

On the Farm • Control of Campylobacter contamination on the farm may

reduce contamination of carcasses, poultry, and red meat products at the retail level.

• Epidemiologic studies indicate that strict hygiene reduces intestinal carriage in food-producing animals.

• In field studies, poultry flocks that drank chlorinated water had lower intestinal colonization rates than poultry that drank unchlorinated water.

• Experimentally, treatment of chicks with commensal bacteria and immunization of older birds reduced C. jejuni colonization.

• Because intestinal colonization with campylobacters readily occurs in poultry flocks, even strict measures may not eliminate intestinal carriage by food-producing animals.

Stern NJ. Mucosal competitive exclusion to diminish colonization of chickens by Campylobacter jejuni. Poult Sci 1994;73:402-7. Widders PR, Perry R, Muir WI, Husband AJ, Long KA. Immunization of chickens to reduce intestinal colonization with Campylobacter jejuni. Br Poult Sci 1996;37:765-8.

1 קמפילובקטר campylobacter c. fetus veneralis c. fetus fetus c. jejuni c. coli c....

Documents

campylobacter jejuni

fetus cell surface

fetus strains

fetus andor

fetus veneralisc

si ming man

nature reviews microbiology

intestinal epithelial