Download קמפילובקטר Campylobacter

‫קמפילובקטר‬
Campylobacter
C. fetus veneralis
C. fetus fetus
C. jejuni / coli
1
‫תכונות‪:‬‬
‫• מתגים דקים‪ ,‬מעוגלים‪ ,‬צורת פסיק‪" ,‬שחף"‪.‬‬
‫• בעלי תנועה (שוטון אחד)‬
‫• מרביתם מיקרואורפיליים (בעבר השתייכו לקב' ‪ vibrio‬לכן‬
‫השם ‪vibriosis‬‬
‫• אינם מפרקים סוכרים אלא מנצלים תוצרי ביניים של מעגל‬
‫ה‪ TCA‬לשם מקור אנרגיה‪.‬‬
‫‪2‬‬
‫תרבית‪:‬‬
‫• דרושים מצעים מיוחדים (תוספת אנטיביוטיקה ‪+‬‬
‫פירובט (כנגד רדיקלים של חמצן)‬
‫• ‪ 5%‬חמצן‪ CO2 10% ,‬ו‪ -%‬גבוה של חנקן‬
‫• צמיחה איטית (‪ 48‬שעות ויותר)‬
‫• לק‪ .‬ונירליס דרוש מצע הובלה מיוחד‬
‫‪3‬‬
‫אנטיגנים‬
‫• ק‪ .‬ג'גוני‪ Heat labile + O antigens :‬משמשים‬
‫לחלוקה לקבוצות סרולוגיות‪.‬‬
‫• תת קבוצות ע"י אנטיגן פלגילרי‪.‬‬
‫‪4‬‬
‫אנטיגנים‬
‫ שכבה‬S-layer (surface array proteins)–SAP :‫ פטוס‬.‫• ק‬
‫חיצונית של המעטפת העשויה חלבונים חומציים והידרופוביים‬
.‫בעלי משקל מולקולרי גבוה‬
.)‫ לתא החיידק (מונע פאגוציטוזס‬C3 ‫• מונעים הצמדת‬
.‫• שונות אנטיגנית בתדירות גבוהה‬
• 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.
‫מימדי של חלבונים אלו קובעים את‬-‫• שינויים במבנה הדו‬
‫קבוצות סרולוגיות ביחד עם‬-‫האימונוגניות ואת החלוקה לתת‬
.‫ של חיידקים אלו‬LPS-‫ של ה‬O-‫אנטיגן ה‬
5
:‫גורמי אלימות‬
• Motility and chemotaxis
– 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
6
:‫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
7
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
8 syndrome.
‫סביבת חיים‬
‫• ‪ C. f. veneralis‬הינו טפיל אובלגטורי של העורלה‬
‫בפרים ומע' המין בפרות נגועות (בתוך חללי הבושת‪,‬‬
‫צוואר הרחם‪ ,‬הרחם והחצוצרות) ‪.‬‬
‫• ‪ C.fetus fetus‬מגיע 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.‬‬
‫‪9‬‬
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.
10
‫בבקר‪ ,‬צאן‪ ,‬כלבים ‪C. jejuni :‬‬
‫• נמצא במע' העיכול ללא סימנים קליניים‪.‬‬
‫• הפלות ספורדיות‪.‬‬
‫• דלקת כבד בעופות‪.‬‬
‫‪12‬‬
‫חתולים‬
‫• לרב ללא סימנים‬
‫• יתכן שלשול מימי‪ ,‬רירי עם או בלי דם‪.‬‬
‫עופות‬
‫• צעירים‪ :‬דלקת מעיים חריפה – שלשול‪ ,‬מוות‬
‫• בוגרים‪ :‬לרב ללא סימנים קליניים‬
‫‪13‬‬
‫העברה‬
‫• העברה אורו‪-‬פקאלית‬
‫• 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.‬‬
‫‪14‬‬
‫בבני אדם ‪C. jejuni :‬‬
‫• שלשול‪ ,‬חום‪ ,‬כאבי‬
‫בטן חריפים‪ ,‬הקאות‬
‫• רמת ההדבקה היא‬
‫‪ 1000/100,000‬איש‪.‬‬
‫• עם פיזור ממע' העיכול יתכנו בקטראמיה‪ ,‬דלקות‬
‫פרקים‪ ,‬מע' השתן‪ ,‬קרומי המוח‪ ,‬אנדוקרדיטיס‪ ,‬קרום‬
‫הבטן‪ ,‬הפלות‪ ,‬זיהום עוברי‪.‬‬
‫• לאחרונה נמצא קשר לתסמונת של ‪acute‬‬
‫‪ polyneuropathy‬ע"ש ‪.Guillain-Barré‬‬
‫‪15‬‬
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
16
Infections Campylobacter jejuni Outbreak of
Associated with Drinking Unpasteurized Milk
Procured Through a Cow-Leasing Program ―
Wisconsin, 2001
During November and December 2001, seventy-five persons from
enteritis. This Campylobacter jejuni Northwestern Wisconsin became ill with
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
.visit this CDC website Campylobacter systems. For more information on
17
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
18
future events .
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 GuillainBarré syndrome. J Infect Dis 1997;176:S125-8.
19
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.
20
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 .
21
fetus infections in adults .Scand J Rheumatol 1994;23:167-70 .
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.
22
‫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 ‪ 3-7‬ימים אך יתכן שלשול לסירוגין‬
‫במשך שבועות‬
‫‪23‬‬
24
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.
25
New York: Plenum Press; 1996. p. 307-11.
Antimicrobial Resistance
• Experimental evidence demonstrates that fluoroquinolonesusceptible 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. Fluoroquinoloneresistant Campylobacter isolated from humans and poultry in Minnesota [abstract].
26
Program
of the 1st International Conference on Emerging Infectious Diseases; Atlanta,
Georgia; 1998 Mar 7-10. Atlanta: Centers for Disease Control and Prevention;1998.
‫‪Campylobacter fetus subsp veneralis‬‬
‫מגע מיני‬
‫פרה‬
‫פר‬
‫‪Campylobacter fetus subsp fetus‬‬
‫צאן‬
‫מעבר‬
‫אוראלי‬
‫זיהום סביבתי‬
‫מזון‬
‫מזוהם?‬
‫אדם‬
‫דרך השליה?‬
‫שליות‪,‬‬
‫נפלים‪,‬‬
‫הפרשות‬
‫צאן‬
‫מגע ישיר?‬
‫אדם‬
‫‪27‬‬
‫‪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
‫‪28‬‬
‫‪infiltration‬‬
‫‪C. fetus veneralis‬‬
‫• יצירה של ‪ IgG‬ברחם 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.‬‬
‫‪29‬‬
‫תסמונת קלינית‬
‫• מחלה תת ‪ -‬קלינית‪ :‬לרוב לא מזוהה‬
‫• בעיה בפוריות‬
‫• חזרה לדרישה ‪ -‬תמותת העובר‬
‫• מעט הפלות (בד"כ פחות מ‪) 10%‬‬
‫• הדבקה דרך מערכת המין בלבד‪.‬‬
‫‪30‬‬
‫‪C. f. fetus‬‬
‫• הדבקה פקו‪ -‬אורלי‬
‫• בד"כ נמצא במערכת העיכול בלבד‬
‫• מעיים ‪ ‬שלפוחית המרה ‪‬כבד‬
‫‪ ‬הריון ‪ ‬בקטראמיה ‪ ‬רחם ‪ ‬שליה‬
‫‪‬דלקת שליה ‪ ‬נקרוזה ‪ ‬לעובר‬
‫‪31‬‬
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
32
‫איבחון מעבדתי‬
‫• בידוד בתרבית ‪ +‬זיהוי‪.‬‬
‫– הבדלה בין הסוגים ע"י בדיקות ביוכימיות‪ ,‬רגישות‬
‫לחומצה נלדיקסית או צפלוטין‪ ,‬וצמיחה ב ‪ 25‬או ‪42‬‬
‫מעלות‪.‬‬
‫•‬
‫•‬
‫•‬
‫•‬
‫שדה אפל‪.‬‬
‫אימונופלואורסנציה‬
‫מבחן סרולוגי ‪ -‬הצמדה‪ -‬לא אמין‬
‫‪PCR‬‬
‫‪33‬‬
‫מניעה וטיפול‬
‫•‬
‫•‬
‫•‬
‫•‬
‫ק‪ .‬ונרליס‪ :‬הזרעה מלאכותית ‪ +‬בדיקת‬
‫הפרים‪.‬‬
‫אנטיביוטיקה בתוך נוזל המשמר של הזירמה‪.‬‬
‫טיפול‪ :‬בדר'כ אוקסטטראציקלין‬
‫חיסון‪ -‬מומת ‪ +‬אדג'ובנט‬
‫‪34‬‬
‫ק‪ .‬פטוס פטוס‪:‬‬
‫• ממשק – נקיון‬
‫• טיפול‪ :‬אוקסטטראציקלין‪ ,‬טילוזין‬
‫• חיסון – בקרוב בארץ‬
‫– גזע תרכיב מתאים לגזעים מקומיים?‬
‫‪35‬‬
‫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.‬‬
‫‪36‬‬
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.
37
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.
Important Tip!
Protect yourself against getting
Campylobacter from animals.
Simply wash your hands with running
water and soap after any contact with
animals and animal feces (stool).
38