International Journal of Food Microbiology, 12 (1991) 1-8 © 1991 Elsevier Science Publishers B.V. 0168-1605/91/$03.50
1
FOOD 00360
Campylobacter: pathogenicity and significance in foods J e a n - P a u l Butzler i a n d J o h a n n e s O o s t e r o m
2
t WHO Collaborating Centrefor Enteric Campylobacter, University Hospital St. Pierre, Brussels, Belgium, and 2 Royal Gist-brocades, Research and Development, Delft, The Netherlands (Received 23 August 1990; accepted 20 September 1990)
In the last 10 years Campylobacter jejuni has emerged as the most frequent cause of bacterial gastroenteritis in man. Acute enterocolitis, the most common presentation of C. jejuni infection, can affect persons of all ages. C. jejuni has been found in virtually every country where investigations have been carried out. The frequent finding of dysenteric stools suggests that mucosal damage due to an invasive process analogous to that seen in shigellosis is important in the pathogenesis. Campylobacteriosis in man is mainly a foodborne infection in which foods of animal origin, particularly poultry, play an important role. Epidemioiogical investigations have demonstrated a significant correlation between the handling and consumption of poultry meat and the occurrence of Campylobacter enteritis. Barbecues appear to present special hazards for infection, because they permit easy transfer of bacteria from raw meats to hands and other foods and from these to the mouth. Milk is sometimes found to be contaminated and consumption of raw milk has caused several outbreaks of campylobacteriosis. Campylobacter can remain viable in fresh cheese for only a short period of time. The organism is also found in shellfish, such as clams. Campyiobacter is probably very vulnerable to factors such as high temperatures and dry environments, and also to the presence of oxygen in atmospheric concentrations. Therefore, it is assumed that the organism does not persist in products like pelleted feed, meals, egg powder and spices, which are often contaminated by Salmonella. A number of preventive measures on different levels, taken simultaneously, are needed to reduce the incidence of campylobacteriosis in man. Key words: Campylobacterjejuni; Infections, foodborne; Enterocolitis, acute; Food hygiene; Prevention
Introduction W i t h i n t h e Campylobacter f a m i l y t h e r e a r e n o w a b o u t s e v e n r e c o g n i s e d s p e c i e s w i t h c l i n i c a l i m p o r t a n c e i n m a n ( T a b l e I) ( G o o s s e n s , 1 9 9 0 ; G o o s s e n s et al., 1990). O f t h e s e , C. jejuni a n d C. coil are b y f a r t h e m o s t f r e q u e n t l y i s o l a t e d f r o m i n d i v i d u a l s w i t h e n t e r i c d i s e a s e ( B u t z l e r et al., 1 9 7 3 ; S k i r r o w , 1977). T h e s e s p e c i e s will t h e r e f o r e b e d i s c u s s e d i n t h i s r e v i e w . S i n c e t h e y a r e a l m o s t i d e n t i c a l i n b e h a v i o u r a n d e p i d e m i o l o g y , w h e r e v e r t h e n a m e C. jejuni is u s e d f u r t h e r o n , C. coli is i m p l i c a t e d a s well.
Correspondence address: J.-P. Butzler, WHO Collaborating Centre for Enteric Campylobacter, University Hospital St. Pierre, 322 Rue Haute, 1000 Brussels, Belgium.
2 TABLE I
Carnpvlobacter species of clinical importance Approved name
Site from which usually isolated
Pathogenicity
C. fetus ssp. fetus
Blood, various other body fluids
Systemic campylobacteriosis in immuno-compromised patients
C. jejuni
Faeces
Acute enterocolitis
C. coil
Faeces
Acute enterocolitis
C. laridis
Faeces
Acute enterocolitis
C. upsaliensis
Faeces
Acute enterocolitis
C cinaedi C fennelliae
Rectal biopsies in homosexuals
Proctitis
C jejuni is commonly found as commensal in poultry, swine, sheep, cattle, dogs, cats, and a number of free-living animals such as birds and rodents (Smibert, 1969; Leuchtefeld et al., 1980; Svedhem et al., 1981; Oosterom, 1985). Most infections in man probably result from consumption of contaminated food and water. Any raw meat meant for consumption may be contaminated with campylobacters. Epidemiological investigations have particularly demonstrated a significant correlation between the handling and consumption of poultry and the occurrence of Carnpylobacter enteritis (WHO, 1984; Oosterom et al., 1984). Raw or inadequately heattreated milk and inadequately treated water have been incriminated as a source of massive outbreaks of infection (Robinson and Jones, 1981; Mentzing, 1981; Vogt et al., 1982). Raw or undercooked beef, hamburgers, sausages and clams have also sporadically been implicated in outbreaks of Campylobacter enteritis, but generally foodborne outbreaks as opposed to sporadic foodborne infections are uncommon. Processors of food and other people involved in food production and preparation are in need of information regarding the organism's pathogenicity, its survival capacities and its association with foods. Therefore, some recommendations for prevention of human campylobacteriosis are discussed in this review as well.
Clinical features of C jejuni infection in humans
Acute enterocolitis is the most common C. jejuni infection (Butzler and Skirrow, 1979; Mandal et al., 1984). The signs and symptoms of C jejuni infections are not very characteristic and it is not possible to clinically differentiate infection by this pathogen from illnesses caused by other pathogens. The incubation period commonly is 2-5 days, but it is estimated that this can extend up to 10 days. In about half of the patients, diarrhoea is preceded by a febrile period with malaise, myalgies
TABLE II Symptoms of C. jejuni enteritis Disease phase
Symptoms
Duration
Prodromal
Malaise; headache; dizziness, anorexia; myalgia; arthralgia; fever Abdominal cramps, profuse diarrhoea: watery or slimy stools containing inflammatory exudate, leucocytes and fresh blood Abdominal pain may persist, dehydration in some cases Appendicular syndrome: cholecystitis; peritonitis; septicaemia; meningitis; arthritis; erythema nodosum
Few hours few days
Diarrhoeic
Recovery Complications
2-10 days
3 days-3 weeks
and abdominal pain; fever of about 40 °C associated with confusion or delirium may be present, fresh blood may appear by the 3rd day. Faecal samples examined microscopically show an inflammatory exudate with leucocytes; moreover it is usually possible to see numerous Campylobacter organisms as well, owing to their characteristic morphology. Vomiting is rare. The diarrhoea remains for about 2-3 days, but abdominal pain and discomfort may persist after the diarrhoea has stopped (Table II). In a significant proportion of patients the infection is manifested as an acute colitis. Sigrnoidoscopy usually reveals abnormalities ranging from mucosal oedema and hyperaemia, either with or without petechial haemorrhage, to mucosal friability. Severe abdominal pain may mimic acute peritonitis. Some patients develop erythema nodosum or reactive arthritis after Campylobacter enteritis whether or not they possess HLA-B27 antigen. Fever is sometimes the only manifestation of C jejuni infection. In several patients the temperature elevation is so severe and persistent that initially typhoid fever is diagnosed until the organism i s isolated from the stool. Bacteraemia has been noted in fewer than 1% of patients with C jejuni infection (Butzler and Skirrow, 1979).
Pathogenesis The mechanism by which C. jejuni causes disease is not well known. The occurrence of infection appears to require adherence of C jejuni to the gut mucosa, perhaps mediated by flagellar adhesins or outer bacterial membrane components. The intestinal mucus gel seems to be a major site for colonisation by C jejuni. One of the mechanisms by which Campylobacter shows its pathogenicity might be the production of toxins. Some of these toxins have a similarity to those of Vibrio cholerae (Goossens, 1990).
The frequent finding of dysenteric stools suggests that mucosal damage due to an invasive process analogous to that seen in shigellosis is also important in the pathogenesis. Indeed, the fact that many patients have erythrocytes and leucocytes in their stools suggests colonic involvement. In cases of Campylobacter colitis, rectal biopsies show decreased numbers of epithelial cells with irregular spacing and reduced mucus production, crypt abscesses and infiltration of the lamina propria with neutrophils, plasma cells and lymphocytes (Mandal et al., 1984). C..]ejuni bacteraemia occasionally occurs, and in such cases the organism is usually isolated both from blood and faeces. Another, less common clinical picture occurs when C. jejuni behaves like Salmonella spp. and Yersinia spp., penetrating the gut mucosa with minimal damage and proliferating in the lamina propria and mesenteric lymph nodes. The clinical picture may mimic acute appendicitis; appendectomies have often been performed in children during outbreaks of Campylobacter enteritis. The brisk antibody response shown in infected patients also indicates the presence of an invasive process. Although the above clinical manifestations suggest different pathogenic mechanisms, they appear to represent extremes of the clinical spectrum caused by the same microorganism. This can for instance be inferred from specific outbreaks caused by unpasteurised milk, which have resulted in both bloody, Shigella-like diarrhoea and the mesenteric adenitis syndrome. The infective dose of C. jejuni varied in different studies from 500 to 100000 organisms. Since the bacterium is sensitive to acid, some of the differences may be explained by variations in gastric pH of the host. Also, strains may vary greatly in virulence. Two strains of C. jejuni ingested by 111 adult volunteers, in doses ranging from 8 x 102 to 2 × 10 9 organisms, caused diarrhoeal illness. All patients had faecal leucocytes. The dysenteric nature of the illness indicated that the pathogenesis of C. jejuni includes tissue inflammation. Ill volunteers developed a serum antibody response to C. jejuni group antigen and were protected from subsequent illness but not from infection with the same strain (Black et al., 1988).
Occurrence of C.
jejuni in foods
Poultry Outbreaks and sporadic cases have been reported due to the consumption of undercooked chicken and chicken livers (Brouwer et al., 1979). Poultry parts and carcasses have been found to be major sources of C. jejuni. C. jejuni contamination has been found in 50-80% of poultry meat products, but lower percentages are also known. In one study, approx. 50% of contaminated livers and gizzards contained more than 1100 C. jejuni organisms per gram (Christopher et al., 1982). Epidemiological investigations have particularly demonstrated a significant correlation between the handling and consumption of poultry meat on one hand and the occurrence of Campylobacter enteritis on the other. This is particularly the case during barbecues and similar events (Oosterom et al., 1984). Homemakers and food
service personnel should be exeptionally careful in handling poultry meat, taking precautions to avoid cross contaminations when preparing meals.
Red meats Although C. jejuni can be frequently isolated from the intestinal contents of pigs, carcasses of slaughtered swine show minimal contamination with C. jejuni. The organism is even practically absent in minced pork, usually a meat product with high general contamination rates. It has been observed that Campylobacter contamination, initially.present on pig carcasses, is eliminated during chilling, mainly through the drying effect of mechanical ventilation (Oosterom et al., 1983). The same effect probably results from the chilling of carcasses of sheep and cattle, so that it may be assumed that these too are free from Campylobacter at the moment they leave the slaughterhouse. Therefore, pork, beef and mutton are not likely to be a source of Campylobacter infection. Poultry carcasses are chilled under conditions different to those for pig carcasses, which means that campylobacters on poultry can remain viable and, in contrast to those on pork, are able to reach the consumer.
Raw milk It is assumed that the presence of Campylobacter in milk can be explained by the occurrence of faecal contamination during milking, but cases of Campylobacter mastitis have also been recorded, and the disease has been reproduced experimentally (Lander and Gill, 1980). The latter would explain the heavy contamination that must occur in order to cause several thousand human infections from one lot of milk (Robinson and Jones, 1981). To prevent milkborne outbreaks, pasteurisation or any other approved heat treatment which kills Camp.vlobacter in all milk sold for human consumption is required (Blaser et al., 1983).
Other foods Other foods might also be contaminated by Campylobacter, in particular those in which meat is present. The organism has indeed been isolated from such products as steak tartar (which is meant to be consumed raw), and an outbreak of C. jejuni enteritis in a Dutch military camp was probably caused by the consumption of raw hamburger (Oosterom et al., 1980). Both these products should be made of pure beef, but often they are (illegally) mixed with pork and poultry meat. In particular the use of poultry meat might result in contamination with Campylobacter. Vegetables and fruits might become contaminated as well if they come into contact with natural fertilisers, wild animals or contaminated waters. Such contamination has been proven so far only in the case of mushrooms (Doyle and Schoeni, 1986). Campylobacter has also been found in shellfish, such as clams (Griffin et al., 1983).
Drinking water Waterborne outbreaks have been described in cases in which drinking water was polluted by faecal contamination, be it caused by free-living birds or by sewage
water after technical problems with the distribution system (Mentzing, 1981: Vogt et al., 1982; Palmer et al., 1983).
Survival of campylobaeters in foods As opposed to salmonellas, campylobacters do not multiply in foods left at ambient temperatures. Campylobacter can generally survive poorly, because of its sensitivity to different environmental factors such as high temperature, low pH (Doyle and Roman, 1981), atmospheric concentration of oxygen (Hoffman et al.. 1979) or the absence of moisture (Doyle and Roman, 1982), which may play a role during long-term exposure of the bacterium on surfaces. Moreover, Campylobacter does not propagate at temperatures below 30°C. This means that 'long-term cross-contaminations', that is contaminations which may show their effect over longer periods of time, for instance in kitchens or hospitals, and which have great importance in the epidemiology of Salmonella, are of minor significance for C. jejuni 'Short-term cross-contamination' mainly occurs by transmission of organisms from contaminated materials directly to the mouth, as may happen for instance during barbecues. Environmental factors are of minor importance in these circumstances. Campylobacter may easily cause infection in man by short-term crosscontamination, in particular with poultry, because of the large numbers of campylobacters initially present. Thus, in comparison with Salmonella, the handling of raw meat or other contaminated products has a far greater significance for
Campylobacter.
Recommendations for prevention (Health Council of The Netherlands, 1988) (1) The occurrence of C. jejuni in slaughter animals should be reduced by measures that include the establishment of Campylobacter-free breeding stocks, the implementation of strict hygiene rules in animal sties, separation of animals from the environment and the supply of germ-free feedstuffs. (2) The routes of transmission of microorganisms from farm animals to man should be blocked by the improvement of hygiene in slaughterhouses and in butchers' shops. If this is not sufficient, decontamination of meat, for instance by irradiation, may be considered. (3) Irradiation of raw meat might particularly be considered with regard to foods for people with a higher risk of infection, such as hospital patients, newborn infants and elderly people.
(4) Because C. jejuni is often present on poultry meat, contact between poultry and other kinds of meat should be prohibited in butchers' shops. These shops should maintain a strict separation between red meat, poultry meat, processed meat products and other foodstuffs. (5) Besides butchers, kitchen personnel and consumers should be informed regularly concerning possible contamination of meat, meat products and other foodstuffs. Moreover, attention should be paid to the importance of rapid heating and cooling of foods and to the hazards of cross-contamination, not only in the kitchen. but also at barbecues and similar situations during which direct contact with raw meat is very likely. (6) The consumption of raw milk and raw or undercooked meat should be discouraged. These foodstuffs might also transmit the causative agents of infectious diseases like salmonellosis, yersiniosis, listeriosis, toxoplasmosis and Q-fever.
References Black, R.E., Levine, M.M., Clements. M.L. and Timothy, P. (1988) Experimental Campvlobacterjejuni infection in humans. J. Infect. Dis. 157, 472-479. Blaser, M.J., Taylor, D.N. and Feidman, R.A. (1983) Epidemiology of Campylobacterjejuni infections. Epidemiol. Reviews 5, 157-176. Brouwer, R., Mertens. M.J.A.. Siem. T.H. and Katchaki, J. (1979) An explosive outbreak of Campvlobacter enteritis in soldiers. Antonie van Leeuwenhoek 45, 517-518. Butzler, J.P. and Skirrow, M.B. (1979) Campvlobacter enteritis. Clin. Gastroenterol. 8. 737-765, Butzler, J.P., Dekeyser, P., Detrain, M. and Dehaen, F. (1973) Related Vibrio in "stools. J. Pediatr. 82, 493-495. Christopher. F.M., Smith, G.C. and Vander-zant. C. (1982) Examination of poultry giblets, raw milk and meat for Campylobacterfetus subsp, jejuni. J. Food Protect. 45, 260-262. Doyle. M.P. and Roman, D.J. (1981) Growth and survival of Campylobacter fetus subsp, jejuni as a function of temperature and pH. J. Food Protect. 44, 596-601. Doyle, M.P. and Roman, D.J. (1982) Sensitivity of Campylobacterjejuni to drying. J. Food Protect. 45, 507-510. Doyle. M.P. and Schocni. J.L. (1986) Isolation of Campylobacterjejuni from retail mushrooms. Appl. Environm. Microbiol. 51,449-450. Goossens. H. (1990) New insights in isolation, taxonomy, pathogenicity and treatment of Camp.vlobacter. Thesis, Free University Brussels. Goossens, H.. Pot, B., Vlaes, L., De Boeck. M.. Kersters, K., Levy, J., De Mol. P., Butzler, J.P. and Vandamme, P. (1990) Is "'C, upsaliensis'" an unrecognised cause of human diarrhoea'?. Lancet 335. 5 8 4 - 586.
Griffin, M.R.. Dalley, E., Fitzpatrick, M. and Austin, S.H. (1983) Campylobacter gastroenteritis associated with raw clams. J. Med. Assoc. New Jersey 80, 607-609. Health Council of The Netherlands (1988) Campylobacter jejuni infections in The Netherlands. The Hague, No. 1988/13E. Hoffman, P.S., Krieg, N.R. and Smibert, R.M. (1979) Studies on the microaerophilic nature of Campylobacter fetus subsp, jejuni. Can. J. Microbiol. 25, 1-7. Lander, K.P. and Gill, K.P.W. (1980) Experimental infection of the bovine udder with Campvlobacter coli/jejuni J. Hyg. (Camb.) 84, 421-428.
Leuchtefeld, N.A.W., Blaser, M.J.. Reiller, L.B. and Wang, W.-L.L. (1980) Isolation of Campylobacter fetus subsp. ,iejuni from migratory waterfowl. J. Clin. Microbiol. 12, 406-408. Mandal, B.K., De Mol, P. and Butzler, J.P. (1984) Clinical aspects of Campylobacter infections in .humans. In: J.P. Butzler (Ed.), Campylobacter Infection in M a n and Animals. C R C Press, Boca Raton, FL, pp. 21-31. Mentzing. L.O. (1981) Waterborne outbreaks of Carnpylobacter enteritis in central Sweden. Lancet ii. 352-354. Oosterom, J. (1985) Studies on the epidemiology of Camp.vlobacterjejuni. Thesis. Erasmus University, Rotterdam. Oosterom, J., Beckers, H.J., van Noorle Jansen. L.M. and van Schothorst, M. (1980) An outbreak of Campylobacter in a barracks, probably caused by eating raw hamburger. Ned. Tijdschr. Geneeskd. 124, 1647-1649. Oosterom, J., de Wilde, G.J.A., de Boer, E.. de Blaauw, L.H. and Karman, H. (1983) Survival of Campylobacterjejuni during poultry processing and pig slaughtering. J. Food Protect. 46, 702-706. Oosterom, J., den Uyl, C.H., B~inffer, J.R.J. and Huisman, J. (1984) Epidemiological investigations on Campvlobacterjejuni in households with a primary infection. J. Hyg. (Camb.) 92, 325-332. Palmer, S.R., Gully, P.R.. White. J.M., Pearson, A.D., Suckling, W.G.. Jones, D.M., Rawes, J.C.L. and Penner, J.L. (1983) Waterborne outbreaks of Campylobacter gastroenteritis. Lancet i, 287-290. Robinson, D.A. and Jones. D.M. (1981) Milk-borne Campylobacter infection. Br. Med. J. 282, 1374-1376. Skirrow, M.B. (1977) Campylobacter enteritis: a "'new" disease. Br. Med. J. ii, 9-11. Smibert, R.M. (1969) Vibrio fetus var. intestinalis isolated from the intestinal content of birds. Am. J. Vet. Res. 30, 1437-1442. Svedhem, A. ad Kaijser. B. (1981) Isolation of Campvlobacterjejuni from domestic animals and pets: probable origin of h u m a n infection. J. Infect. 3. 37-40. Vogt, R.L., Sours, H.E., Barrett, T., Feldman, R.A., Dickinson, R.J. and Witherell, L. (1982) Campylobacter enteritis associated with contaminated water. Ann. Intern. Med. 96, 292-296. World Health Organization (1984) Report of the W H O consultation on veterinary public health aspects of prevention and control of Campylobacter infection. Geneva, V P H / C D D / F O S / 8 4 . 1 .
1
FOOD 00360
Campylobacter: pathogenicity and significance in foods J e a n - P a u l Butzler i a n d J o h a n n e s O o s t e r o m
2
t WHO Collaborating Centrefor Enteric Campylobacter, University Hospital St. Pierre, Brussels, Belgium, and 2 Royal Gist-brocades, Research and Development, Delft, The Netherlands (Received 23 August 1990; accepted 20 September 1990)
In the last 10 years Campylobacter jejuni has emerged as the most frequent cause of bacterial gastroenteritis in man. Acute enterocolitis, the most common presentation of C. jejuni infection, can affect persons of all ages. C. jejuni has been found in virtually every country where investigations have been carried out. The frequent finding of dysenteric stools suggests that mucosal damage due to an invasive process analogous to that seen in shigellosis is important in the pathogenesis. Campylobacteriosis in man is mainly a foodborne infection in which foods of animal origin, particularly poultry, play an important role. Epidemioiogical investigations have demonstrated a significant correlation between the handling and consumption of poultry meat and the occurrence of Campylobacter enteritis. Barbecues appear to present special hazards for infection, because they permit easy transfer of bacteria from raw meats to hands and other foods and from these to the mouth. Milk is sometimes found to be contaminated and consumption of raw milk has caused several outbreaks of campylobacteriosis. Campylobacter can remain viable in fresh cheese for only a short period of time. The organism is also found in shellfish, such as clams. Campyiobacter is probably very vulnerable to factors such as high temperatures and dry environments, and also to the presence of oxygen in atmospheric concentrations. Therefore, it is assumed that the organism does not persist in products like pelleted feed, meals, egg powder and spices, which are often contaminated by Salmonella. A number of preventive measures on different levels, taken simultaneously, are needed to reduce the incidence of campylobacteriosis in man. Key words: Campylobacterjejuni; Infections, foodborne; Enterocolitis, acute; Food hygiene; Prevention
Introduction W i t h i n t h e Campylobacter f a m i l y t h e r e a r e n o w a b o u t s e v e n r e c o g n i s e d s p e c i e s w i t h c l i n i c a l i m p o r t a n c e i n m a n ( T a b l e I) ( G o o s s e n s , 1 9 9 0 ; G o o s s e n s et al., 1990). O f t h e s e , C. jejuni a n d C. coil are b y f a r t h e m o s t f r e q u e n t l y i s o l a t e d f r o m i n d i v i d u a l s w i t h e n t e r i c d i s e a s e ( B u t z l e r et al., 1 9 7 3 ; S k i r r o w , 1977). T h e s e s p e c i e s will t h e r e f o r e b e d i s c u s s e d i n t h i s r e v i e w . S i n c e t h e y a r e a l m o s t i d e n t i c a l i n b e h a v i o u r a n d e p i d e m i o l o g y , w h e r e v e r t h e n a m e C. jejuni is u s e d f u r t h e r o n , C. coli is i m p l i c a t e d a s well.
Correspondence address: J.-P. Butzler, WHO Collaborating Centre for Enteric Campylobacter, University Hospital St. Pierre, 322 Rue Haute, 1000 Brussels, Belgium.
2 TABLE I
Carnpvlobacter species of clinical importance Approved name
Site from which usually isolated
Pathogenicity
C. fetus ssp. fetus
Blood, various other body fluids
Systemic campylobacteriosis in immuno-compromised patients
C. jejuni
Faeces
Acute enterocolitis
C. coil
Faeces
Acute enterocolitis
C. laridis
Faeces
Acute enterocolitis
C. upsaliensis
Faeces
Acute enterocolitis
C cinaedi C fennelliae
Rectal biopsies in homosexuals
Proctitis
C jejuni is commonly found as commensal in poultry, swine, sheep, cattle, dogs, cats, and a number of free-living animals such as birds and rodents (Smibert, 1969; Leuchtefeld et al., 1980; Svedhem et al., 1981; Oosterom, 1985). Most infections in man probably result from consumption of contaminated food and water. Any raw meat meant for consumption may be contaminated with campylobacters. Epidemiological investigations have particularly demonstrated a significant correlation between the handling and consumption of poultry and the occurrence of Carnpylobacter enteritis (WHO, 1984; Oosterom et al., 1984). Raw or inadequately heattreated milk and inadequately treated water have been incriminated as a source of massive outbreaks of infection (Robinson and Jones, 1981; Mentzing, 1981; Vogt et al., 1982). Raw or undercooked beef, hamburgers, sausages and clams have also sporadically been implicated in outbreaks of Campylobacter enteritis, but generally foodborne outbreaks as opposed to sporadic foodborne infections are uncommon. Processors of food and other people involved in food production and preparation are in need of information regarding the organism's pathogenicity, its survival capacities and its association with foods. Therefore, some recommendations for prevention of human campylobacteriosis are discussed in this review as well.
Clinical features of C jejuni infection in humans
Acute enterocolitis is the most common C. jejuni infection (Butzler and Skirrow, 1979; Mandal et al., 1984). The signs and symptoms of C jejuni infections are not very characteristic and it is not possible to clinically differentiate infection by this pathogen from illnesses caused by other pathogens. The incubation period commonly is 2-5 days, but it is estimated that this can extend up to 10 days. In about half of the patients, diarrhoea is preceded by a febrile period with malaise, myalgies
TABLE II Symptoms of C. jejuni enteritis Disease phase
Symptoms
Duration
Prodromal
Malaise; headache; dizziness, anorexia; myalgia; arthralgia; fever Abdominal cramps, profuse diarrhoea: watery or slimy stools containing inflammatory exudate, leucocytes and fresh blood Abdominal pain may persist, dehydration in some cases Appendicular syndrome: cholecystitis; peritonitis; septicaemia; meningitis; arthritis; erythema nodosum
Few hours few days
Diarrhoeic
Recovery Complications
2-10 days
3 days-3 weeks
and abdominal pain; fever of about 40 °C associated with confusion or delirium may be present, fresh blood may appear by the 3rd day. Faecal samples examined microscopically show an inflammatory exudate with leucocytes; moreover it is usually possible to see numerous Campylobacter organisms as well, owing to their characteristic morphology. Vomiting is rare. The diarrhoea remains for about 2-3 days, but abdominal pain and discomfort may persist after the diarrhoea has stopped (Table II). In a significant proportion of patients the infection is manifested as an acute colitis. Sigrnoidoscopy usually reveals abnormalities ranging from mucosal oedema and hyperaemia, either with or without petechial haemorrhage, to mucosal friability. Severe abdominal pain may mimic acute peritonitis. Some patients develop erythema nodosum or reactive arthritis after Campylobacter enteritis whether or not they possess HLA-B27 antigen. Fever is sometimes the only manifestation of C jejuni infection. In several patients the temperature elevation is so severe and persistent that initially typhoid fever is diagnosed until the organism i s isolated from the stool. Bacteraemia has been noted in fewer than 1% of patients with C jejuni infection (Butzler and Skirrow, 1979).
Pathogenesis The mechanism by which C. jejuni causes disease is not well known. The occurrence of infection appears to require adherence of C jejuni to the gut mucosa, perhaps mediated by flagellar adhesins or outer bacterial membrane components. The intestinal mucus gel seems to be a major site for colonisation by C jejuni. One of the mechanisms by which Campylobacter shows its pathogenicity might be the production of toxins. Some of these toxins have a similarity to those of Vibrio cholerae (Goossens, 1990).
The frequent finding of dysenteric stools suggests that mucosal damage due to an invasive process analogous to that seen in shigellosis is also important in the pathogenesis. Indeed, the fact that many patients have erythrocytes and leucocytes in their stools suggests colonic involvement. In cases of Campylobacter colitis, rectal biopsies show decreased numbers of epithelial cells with irregular spacing and reduced mucus production, crypt abscesses and infiltration of the lamina propria with neutrophils, plasma cells and lymphocytes (Mandal et al., 1984). C..]ejuni bacteraemia occasionally occurs, and in such cases the organism is usually isolated both from blood and faeces. Another, less common clinical picture occurs when C. jejuni behaves like Salmonella spp. and Yersinia spp., penetrating the gut mucosa with minimal damage and proliferating in the lamina propria and mesenteric lymph nodes. The clinical picture may mimic acute appendicitis; appendectomies have often been performed in children during outbreaks of Campylobacter enteritis. The brisk antibody response shown in infected patients also indicates the presence of an invasive process. Although the above clinical manifestations suggest different pathogenic mechanisms, they appear to represent extremes of the clinical spectrum caused by the same microorganism. This can for instance be inferred from specific outbreaks caused by unpasteurised milk, which have resulted in both bloody, Shigella-like diarrhoea and the mesenteric adenitis syndrome. The infective dose of C. jejuni varied in different studies from 500 to 100000 organisms. Since the bacterium is sensitive to acid, some of the differences may be explained by variations in gastric pH of the host. Also, strains may vary greatly in virulence. Two strains of C. jejuni ingested by 111 adult volunteers, in doses ranging from 8 x 102 to 2 × 10 9 organisms, caused diarrhoeal illness. All patients had faecal leucocytes. The dysenteric nature of the illness indicated that the pathogenesis of C. jejuni includes tissue inflammation. Ill volunteers developed a serum antibody response to C. jejuni group antigen and were protected from subsequent illness but not from infection with the same strain (Black et al., 1988).
Occurrence of C.
jejuni in foods
Poultry Outbreaks and sporadic cases have been reported due to the consumption of undercooked chicken and chicken livers (Brouwer et al., 1979). Poultry parts and carcasses have been found to be major sources of C. jejuni. C. jejuni contamination has been found in 50-80% of poultry meat products, but lower percentages are also known. In one study, approx. 50% of contaminated livers and gizzards contained more than 1100 C. jejuni organisms per gram (Christopher et al., 1982). Epidemiological investigations have particularly demonstrated a significant correlation between the handling and consumption of poultry meat on one hand and the occurrence of Campylobacter enteritis on the other. This is particularly the case during barbecues and similar events (Oosterom et al., 1984). Homemakers and food
service personnel should be exeptionally careful in handling poultry meat, taking precautions to avoid cross contaminations when preparing meals.
Red meats Although C. jejuni can be frequently isolated from the intestinal contents of pigs, carcasses of slaughtered swine show minimal contamination with C. jejuni. The organism is even practically absent in minced pork, usually a meat product with high general contamination rates. It has been observed that Campylobacter contamination, initially.present on pig carcasses, is eliminated during chilling, mainly through the drying effect of mechanical ventilation (Oosterom et al., 1983). The same effect probably results from the chilling of carcasses of sheep and cattle, so that it may be assumed that these too are free from Campylobacter at the moment they leave the slaughterhouse. Therefore, pork, beef and mutton are not likely to be a source of Campylobacter infection. Poultry carcasses are chilled under conditions different to those for pig carcasses, which means that campylobacters on poultry can remain viable and, in contrast to those on pork, are able to reach the consumer.
Raw milk It is assumed that the presence of Campylobacter in milk can be explained by the occurrence of faecal contamination during milking, but cases of Campylobacter mastitis have also been recorded, and the disease has been reproduced experimentally (Lander and Gill, 1980). The latter would explain the heavy contamination that must occur in order to cause several thousand human infections from one lot of milk (Robinson and Jones, 1981). To prevent milkborne outbreaks, pasteurisation or any other approved heat treatment which kills Camp.vlobacter in all milk sold for human consumption is required (Blaser et al., 1983).
Other foods Other foods might also be contaminated by Campylobacter, in particular those in which meat is present. The organism has indeed been isolated from such products as steak tartar (which is meant to be consumed raw), and an outbreak of C. jejuni enteritis in a Dutch military camp was probably caused by the consumption of raw hamburger (Oosterom et al., 1980). Both these products should be made of pure beef, but often they are (illegally) mixed with pork and poultry meat. In particular the use of poultry meat might result in contamination with Campylobacter. Vegetables and fruits might become contaminated as well if they come into contact with natural fertilisers, wild animals or contaminated waters. Such contamination has been proven so far only in the case of mushrooms (Doyle and Schoeni, 1986). Campylobacter has also been found in shellfish, such as clams (Griffin et al., 1983).
Drinking water Waterborne outbreaks have been described in cases in which drinking water was polluted by faecal contamination, be it caused by free-living birds or by sewage
water after technical problems with the distribution system (Mentzing, 1981: Vogt et al., 1982; Palmer et al., 1983).
Survival of campylobaeters in foods As opposed to salmonellas, campylobacters do not multiply in foods left at ambient temperatures. Campylobacter can generally survive poorly, because of its sensitivity to different environmental factors such as high temperature, low pH (Doyle and Roman, 1981), atmospheric concentration of oxygen (Hoffman et al.. 1979) or the absence of moisture (Doyle and Roman, 1982), which may play a role during long-term exposure of the bacterium on surfaces. Moreover, Campylobacter does not propagate at temperatures below 30°C. This means that 'long-term cross-contaminations', that is contaminations which may show their effect over longer periods of time, for instance in kitchens or hospitals, and which have great importance in the epidemiology of Salmonella, are of minor significance for C. jejuni 'Short-term cross-contamination' mainly occurs by transmission of organisms from contaminated materials directly to the mouth, as may happen for instance during barbecues. Environmental factors are of minor importance in these circumstances. Campylobacter may easily cause infection in man by short-term crosscontamination, in particular with poultry, because of the large numbers of campylobacters initially present. Thus, in comparison with Salmonella, the handling of raw meat or other contaminated products has a far greater significance for
Campylobacter.
Recommendations for prevention (Health Council of The Netherlands, 1988) (1) The occurrence of C. jejuni in slaughter animals should be reduced by measures that include the establishment of Campylobacter-free breeding stocks, the implementation of strict hygiene rules in animal sties, separation of animals from the environment and the supply of germ-free feedstuffs. (2) The routes of transmission of microorganisms from farm animals to man should be blocked by the improvement of hygiene in slaughterhouses and in butchers' shops. If this is not sufficient, decontamination of meat, for instance by irradiation, may be considered. (3) Irradiation of raw meat might particularly be considered with regard to foods for people with a higher risk of infection, such as hospital patients, newborn infants and elderly people.
(4) Because C. jejuni is often present on poultry meat, contact between poultry and other kinds of meat should be prohibited in butchers' shops. These shops should maintain a strict separation between red meat, poultry meat, processed meat products and other foodstuffs. (5) Besides butchers, kitchen personnel and consumers should be informed regularly concerning possible contamination of meat, meat products and other foodstuffs. Moreover, attention should be paid to the importance of rapid heating and cooling of foods and to the hazards of cross-contamination, not only in the kitchen. but also at barbecues and similar situations during which direct contact with raw meat is very likely. (6) The consumption of raw milk and raw or undercooked meat should be discouraged. These foodstuffs might also transmit the causative agents of infectious diseases like salmonellosis, yersiniosis, listeriosis, toxoplasmosis and Q-fever.
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