1. קמפילובקטר Campylobacter
C. fetus veneralis
C. fetus fetus
C. jejuni
C. coli
C. upsaliensis
C. lari
C. hyointestinalis

2. קמפילובקטר Campylobacter
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
C. upsaliensis
Dogs cats poultry
Asymp diarrhea
C. lari
Wild birds dogs
C. hyointestinalis
Poultry cattle sheep dogs cats pigs pets

3. תכונות: מתגים דקים, מעוגלים, צורת פסיק, "שחף". בעלי תנועה (שוטון אחד)
מרביתם מיקרואורפיליים
(בעבר השתייכו לקב' vibrio לכן השם vibriosis
אינם מפרקים סוכרים אלא מנצלים תוצרי ביניים של מעגל הTCA לשם מקור אנרגיה.

4. תרבית:
דרושים מצעים מיוחדים (תוספת אנטיביוטיקה + פירובט (כנגד רדיקלים של חמצן)
5% חמצן, 10% CO2 ו%- גבוה של חנקן
צמיחה איטית (48 שעות ויותר)
לק. ונירליס דרוש מצע הובלה מיוחד

5. אנטיגנים
ק. ג'גוני: Heat labile + O antigens משמשים לחלוקה לקבוצות סרולוגיות.
תת קבוצות ע"י אנטיגן פלגילרי.

6. אנטיגנים
ק. פטוס: S-layer (surface array proteins)–SAP שכבה חיצונית של המעטפת העשויה חלבונים חומציים והידרופוביים בעלי משקל מולקולרי גבוה.
שינויים במבנה הדו-מימדי של חלבונים אלו קובעים את האימונוגניות ואת החלוקה לתת-קבוצות סרולוגיות ביחד עם אנטיגן ה-O של ה-LPS של חיידקים אלו.
Campylobacter Surface-Layers (S-Layers) and Immune Evasion
Dr. Stuart A. Thompson Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, Georgia.
Many pathogenic bacteria have evolved mechanisms for evading host immune systems. One evasion mechanism is manifest by the surface layer (S-layer), a paracrystalline protein structure composed of S-layer proteins (SLPs). The S-layer, possessed by 2 Campylobacter species (C. fetus and C. rectus), is external to the bacterial outer membrane and can have multiple functions in immune avoidance. C. fetus is a pathogen of ungulates and immunocompromised humans, in whom it causes disseminated bloodstream disease. In C. fetus, the S-layer is required for dissemination and is involved in 2 mechanisms of evasion. First, the S-layer confers resistance to complementmediated 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 complementindependent killing, utilizing opsonic antibodies directed against the S-layer. However, C. fetus has also evolved a mechanism for avoiding antibody-mediated killing by high-frequency antigenic variation of SLPs. Antigenic variation is accomplished by complex DNA inversion events involving a family of multiple SLPencoding genes and a single SLP promoter. Inversion events result in the expression of antigenically variant S-layers, which require distinct antibody responses for killing. C. rectus is implicated in the pathogenesis of periodontal disease and also possesses an S-layer that appears to be involved in evading the human system. Although studied less extensively than its C. fetus counterpart, the C. rectus S-layer appears to confer resistance to complement-mediated killing and to cause the down-regulation of proinflammatory cytokines. Ann Periodontol 2002;7:43-53.
Campylobacter jejuni: molecular biology and pathogenesis , Kathryn T. Young, Lindsay M. Davis & Victor J. DiRita, Nature Reviews Microbiology 5, (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.
The C. jejuni cell surface displays several structures, including many polysaccharides, that have vital roles in C. jejuni biology, particularly host–bacterium interactions.
The capsule, a highly variable polysaccharide, is important for virulence, epithelial cell adherence and invasion.
The lipooligosaccharide (LOS) is also highly variable and has a role in serum resistance, epithelial cell adherence and invasion. LOS structures of C. jejuni can display molecular mimicry of neuronal gangliosides, which is linked to Guillain–Barré syndrome and Miller–Fisher syndrome.
The flagellum is required for colonization, virulence and epithelial cell invasion and also acts as a secretion apparatus for invasion antigens. The flagellin is modified by O-linked glycosylation. This modification is required for flagellar assembly and is, therefore, important for motility, virulence and epithelial cell adherence and invasion.
The N-linked-glycosylation system modifies some periplasmic and outer-membrane proteins. The N-linked glycan is also important for colonization and epithelial cell adherence and invasion, but the role of this glycan in these processes is unclear.

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

9. Mucosa-associated bacteria have the capacity to swim through the mucus layer that covers the intestinal epithelium.
Attach to and invade intestinal epithelial cells (C. coli, C. concisus, C. fetus, C. rectus and C. upsaliensis)
The clinical importance of emerging Campylobacter species, Si Ming Man, Nature Reviews Gastroenterology & Hepatology 8, (2011)

10. Translocate across the intestinal epithelium either via a transcellular route (C. fetus) and/or via a paracellular route by breaking down barrier-associated tight junctions (C. concisus).
The clinical importance of emerging Campylobacter species, Si Ming Man, Nature Reviews Gastroenterology & Hepatology 8, (2011)

11. גורמי אלימות: Intracellular : Proteins and enzymes
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

12. Deliver effector proteins into host epithelial cells via a putative T4SS (C. fetus, C. coli).
The clinical importance of emerging Campylobacter species, Si Ming Man, Nature Reviews Gastroenterology & Hepatology 8, (2011)

13. The S-layer mediates resistance to phagocytosis and serum-killing (C
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 systemic phase of infection.
The clinical importance of emerging Campylobacter species, Si Ming Man, Nature Reviews Gastroenterology & Hepatology 8, (2011)

14. 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 cell surface is mediated by CdtA and CdtC, followed by delivery of CdtB into the host nucleus, which initiates cell cycle arrest and DNA damage.
The clinical importance of emerging Campylobacter species, Si Ming Man, Nature Reviews Gastroenterology & Hepatology 8, (2011)

15. Other toxins include cell-bound and secreted hemolysins, which have the capacity to lyse red blood cells (C. coli and C. concisus).
The clinical importance of emerging Campylobacter species, Si Ming Man, Nature Reviews Gastroenterology & Hepatology 8, (2011)

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.
מרבית האחרים :commensals של מע' העיכול 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.

19. פתוגניות C. jejuni / C.coli
חיידק אינבסיבי (invasive ) אשר מאכלס במהירות את הריר ואת הרירית של מע' העיכול. משיכה (chemotaxis ) למוסין (mucin ) שהוא המרכיב העיקרי של ריר, ומסוגל לנצלו כמקור מזון.
יכולת החדירה תלויה בתנועתיות (פלגלה). במידה ויש חדירה דרך המעי הדק מתפתחת בקטרמיה והמשך התמקמות באברי מטרה ( כבד בעופות, רחם בבקר וצאן).
produces an adhesin, a cytotoxin and a heat labile toxin (LPS) similar to E. coli.

20. בבקר, צאן, כלבים : C. jejuni
נמצא במע' העיכול ללא סימנים קליניים.
הפלות ספורדיות.
דלקת כבד בעופות.

21. חתולים עופות לרב ללא סימנים יתכן שלשול מימי, רירי עם או בלי דם.
צעירים: דלקת מעיים חריפה – שלשול, מוות
בוגרים: לרב ללא סימנים קליניים

22. העברה העברה אורו-פקאלית מקורות: מצב של נשאות בבע"ח אך בד"כ לא באדם.
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.

23. בבני אדם : C. jejuni שלשול, חום, כאבי בטן חריפים, הקאות
רמת ההדבקה היא 1000/100,000 איש.
עם פיזור ממע' העיכול יתכנו בקטראמיה, דלקות פרקים, מע' השתן, קרומי המוח, אנדוקרדיטיס, קרום הבטן, הפלות, זיהום עוברי.
לאחרונה נמצא קשר לתסמונת של acute polyneuropathy ע"ש Guillain-Barré.

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. PRESS CONTACT: Donita Croft, MD, MS Wisconsin Division of Public Health (608) 267–9004
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:

32. A survey of Campylobacter in animals. Manser PA, Dalziel RW
A survey of Campylobacter in animals. Manser PA, Dalziel RW.,Hyg (Lond) 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 ב1.6% עד 28% מכלבים ללא סימנים קליניים.
בצעירים או במקרים מיוחדים תתכן תחלואה:
שלשול מימי עם מרה, ריר ויתכן דם
הקאות
חוסר תיאבון
+/- חום
נמשך בד"כ 3-7 ימים אך יתכן שלשול לסירוגין 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; p

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 Atlanta: Centers for Disease Control and Prevention;1998.

37. Campylobacter fetus subsp veneralis
מגע מיני
פרה פר
Campylobacter fetus subsp fetus
שליות, נפלים, הפרשות
צאן
מעבר אוראלי
צאן
זיהום סביבתי
מגע ישיר?
מזון מזוהם?
דרך השליה?
אדם
אדם

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
יצירה של IgG ברחם ו- IgA בבושת המונעים 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 בעיה בפוריות
חזרה לדרישה - תמותת העובר
מעט הפלות (בד"כ פחות מ10% )
הדבקה דרך מערכת המין בלבד.

41. C. f. fetus הדבקה פקו- אורלי בד"כ נמצא במערכת העיכול בלבד
מעיים  שלפוחית המרה כבד
הריון  בקטראמיה  רחם  שליה דלקת שליה  נקרוזה  לעובר

42. Campylobacter fetus in man
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

43. איבחון מעבדתי בידוד בתרבית + זיהוי. אימונופלואורסנציה
הבדלה בין הסוגים ע"י בדיקות ביוכימיות, רגישות לחומצה נלדיקסית או צפלוטין, וצמיחה ב 25 או 42 מעלות.
Phase contrast microscopy
אימונופלואורסנציה
מבחן סרולוגי - הצמדה- לא אמין
PCR

44. מניעה וטיפול ק. ונרליס: הזרעה מלאכותית + בדיקת הפרים.
אנטיביוטיקה בתוך נוזל המשמר של הזירמה.
טיפול: בדר'כ אוקסטטראציקלין
חיסון- מומת + אדג'ובנט

45. ק. פטוס פטוס: ממשק – נקיון טיפול: אוקסטטראציקלין, טילוזין
חיסון – בקרוב בארץ
גזע תרכיב מתאים לגזעים מקומיים?

46. 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.