COHORT STUDY OF INTESTINAL INFECTION WITH CAMPYLOBACTER IN MEXICAN CHILDREN

503 the apparent tissue

specificity

in the

expression

COHORT STUDY OF INTESTINAL

of clinical

INFECTION WITH CAMPYLOBACTER IN

symptoms. However, it is

more likely that there is molecular heterogeneity underlying complex-I deficiency. The specific polypeptide defect detected in patient 3 was in a nuclear encoded subunit. The lack of family history in this patient suggests that her defect arose as the result of a

spontaneous mutation in the nuclear genome. A defect in a

mitochondrially encoded polypeptide, and so the prospect of disease transmission by maternal (mitochondrial) inheritance in the other two patients, has not been excluded by these results. The study of patients with specific defects of the respiratory chain provides a unique opportunity not only to improve our understanding of the structure, function, and integration of the enzymes in the normal respiratory chain, but may also provide insight into any cooperation or collaboration between the nuclear and mitochondrial genomes. We thank the Muscular Dystrophy Group of Great Britain, the Brain Research Trust, and the Science and Engineering Research Council for their support; Dr A. M. Whitely for referring patient 2; Miss Marjorie Ellison for technical assistance, and Mrs Kathryn Aziz for preparing the script. A. H. V. S. was in receipt of a Wellcome Fellowship.

MEXICAN CHILDREN GUILLERMO M. RUIZ-PALACIOS ANCELMO RAMOS ANA B. LOPEZ-VIDAL ROSSANA BOJALIL

JUAN J. CALVA

Department of Infectious Diseases, Instituto Nacional de la Nutricion, Vasco de Quiroga 15, Tlalpan, Mexico 14000 DF, Mexico

Summary was

A cohort of 179 children under 5 years of age from a low-income urban community

followed up for

a

year to determine the incidence of

symptom-producing and of diarrhoea-free campylobacter intestinal infections, and thus their illness-to-infection ratio. 66% of all children had at least one campylobacter infection, one-third of these being associated with diarrhoea. The annual incidence of all campylobacter infections was 2·1 episodes per child. The incidence was inversely related to The illness-to-infection ratio, age (r = - 0·78 p<0·02). which in infants younger than 6 months was 1:2, was negatively associated with age (r = -0·7, p<0·02). Only symptom-producing infections occurring early in life seemed to protect against subsequent infections.

REFERENCES

Introduction 1.

Morgan-Hughes JA. The mitochondrial myopathies. In Engel AG, Banker BQ, eds Myology. New York McGraw-Hill, 1986: 1709-43. 2.Di Mauro S, Bonilla E, Zeviani M, Nakagawa M, de Vivo D. Mitochondrial myopathies. Ann Neurol 1985; 17: 521-38. 3. Morgan-Hughes JA Mitochondrial diseases. Trends Neurosci 1986; 9: 15-19 4. Anderson S, Bankier AT, Barrell BG, et al. Sequence and organisation of the human mitochondrial genome. Nature 1981; 290: 457-65. 5. Chomyn A, Manottmi P, Cleeter MWJ, et al. Functional assignment of the products of the unidentified reading frames of human mitochondrial DNA. In Quagliarello E, ed. Achievements and perspectives of mitochondrial research. Amsterdam: Elsevier, 1985 259-75. 6. Egger J, Wilson J Mitochondrial inheritance in a mitochondrially mediated disease. N Engl J Med 1983; 309: 142-46 7 Rosing HS, Hopkms LC, Wallace DC, Epstein CM, Weidenheim K. Maternally inherited mitochondrial myopathy and myoclonic epilepsy. Ann Neurol 1985; 17: 228-37. 8. Morgan-Hughes JA, Hayes DJ, Cooper M, Clark JB. Mitochondrial myopathies: deficiencies localised to Complex I and Complex III of the mitochondrial respiratory chain. Biochem Soc Trans 1985; 13: 648-50. 9. Morgan-Hughes JA, Cooper JM, Schapira AHV, Hayes DJ, Clark JB. The mitochondrial myopathies. Defects of the mitochondrial respiratory chain and oxidative phosphorylation In. Ellmgson RJ, Murray NMF, Halliday AM, eds. The London Symposia (EEG suppl 39): Amsterdam: Elsevier, 1987: 103-14. 10. Di Mauro S, Zeviani M, Bonilla E, et al. Cytochrome c oxidase deficiency Biochem Soc Trans 1985, 13: 651-53. 11. Chomyn A, Mariottini P, Cleeter MWJ, et al. Six unidentified reading frames of human mitochondrial DNA encode components of the respiratory chain NADH dehydrogenase Nature 1985; 314: 592-97. 12. Tzagoloff A, Mitochondria. New York Plenum Press, 1982. 13 Cleeter MWJ, Bannister SH, Ragan CI. Chemical cross-linking of mitochondrial NADH dehydrogenase from bovine heart. Biochem J 1985; 227: 467-74. 14. Morgan-Hughes JA, Darvemza P, Landon DN, Land JM, Clark JB A mitochondrial myopathy characterised by a deficiency in reducible cytochrome b Brain 1977; 100: 617-40. 15. Lowry HO, Rosebrough NJ, Lewis Fanr A, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193: 265-75. 16. Laemmli UK Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680-85. 17 Towbm H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: Procedure and some applications. Proc Natl Acad Sci USA 1979; 76: 4350-54. 18 Heron C, Smith S, Ragan CI An analysis of the polypepude composition of bovine heart mitochondrial NADH-ubiquinone oxidoreductase by 2 D-PAGE Biochem J 1979; 181: 435-43 19. Gondal JA, Anderson WM. The molecular morphology of bovine heart mitrochondrial NADH-ubiquinone reductase. J Biol Chem 1985, 260: 12690-94. 20. Hare JF, Hodges R Turnover of mitochondrial inner membrane proteins in hepatoma monolayer cultures J Biol Chem 1982; 257: 3575-80. 21 Sen K,Beattie DS. Decreased amounts of core proteins I and II and the FeS protein in mitochondria from yeast lacking cytochrome b but containing cytochrome c1. Arch Biochem Biophys 1985; 242: 393-401. 22. Darley-Usmar VM, Kennaway NG, Buist NRM, Capaldi RA Deficiency in ubiquinone cytochrome c reductase in a patient with mitochondrial myopathy and lactic acidosis Proc Natl Acad Sci USA 1983; 80: 5103-06. 23. Tzagaloff A, Myers AM. Genetics of mitochondrial biogenesis. Ann Rev Biochem 1986; 55: 249-86. 24. Merle P, Kadenbach B Kinetic and structural differences between cytochrome c oxidases from beef, liver and heart Eur J Biochem 1982; 125: 239-44

Campylobacter jejuni is one of the leading causes of infectious diarrhoea in children.1,2 In several communitybased surveys C jejuni was the most commonly isolated enteropathogen in diarrhoeal stools from children aged under 5 years; such was also the case in a low-income population in Mexico City.4 In developed countries C jejuni intestinal infection is almost uniformly associated with disease and symptomless excretion is uncommon. In developing countries the epidemiological features are different. Cross-sectional studies in Africa and Asia have shown that C jejuni may be isolated from 1-5-17-7% of stool samples from diarrhoeafree children.2 In Bangladesh, up to 32% of symptomless infants had enteric colonisation by C jejuni and this proportion declined with increasing age ;5 and among Bangladeshi family contacts of diarrhoeal patients with campylobacter young children were more frequently infected and had a higher illness-to-infection ratio with C jejuni than did older members of the family.6 Healthy rural Bangladeshi7 and Thai8 children have significantly higher levels of specific antibodies to C jejuni than do age-matched healthy children in the United States, and in the Bangladeshi and Thai children specific IgA rises progressively with age. These data have led to the hypothesis that in children from developing countries the possible development of immunity early in life could account for their high rate of C jejuni diarrhoea-free intestinal infection and for their lower illness-to-infection ratio with increasing age. However, most of the studies cited were cross-sectional, with no assessment of the relative frequency of symptom-producing and symptomless C jejuni infections over time. To obtain evidence for the hypothesis we have conducted a community-based prospective longitudinal study of a cohort of young children living in a low-income urban area in Mexico City, highly endemic for diarrhoeal diseases, to determine the association between age and the rate of diarrhoea-associated campylobacter infection, the incidence of symptom-free carriage states, and the illness-to-infection ratio.

504

Methods

Study Population This study was conducted in San Pedro Martir, a low-income urban area on the southwestern outskirts of Mexico City. There are predominantly three socioeconomic groups among the approximately 35 000 inhabitants-original residents of the area, immigrants from rural areas who have settled in, and more recent rural immigrants (who are more likely to be unemployed). Since 1983 our team has been providing health care as well as gathering information in a local clinic for diarrhoeal diseases. Mothers living in this community with children under age 5 years were invited to participate in the study. Enrolment continued throughout the year of study so follow up was less than 12 months for some children. To be eligible children had to belong to a family that was planning to stay in the community during the study and they had to have no chronic illnesses (other than diarrhoea or malnourishment) or a history of milk allergy.

Epidemiological Surveillance A field worker visited every household twice a week to interview the child’s mother. At every visit, characteristics of the child’s stools (daily number, consistency, and presence of blood) since the previous visit were inquired about and recorded. To check on the accuracy of these data a supervisor paid unexpected household visits to collect the same information, whenever there were important discrepancies in data the mother was interviewed again. Stool samples from every child were checked weekly for campylobacter, and for all pathogens whenever diarrhoea occurred. With most children, 3-5 ml of blood was drawn from a peripheral vein when they first entered the study and then 6 months later.

Stool

Samples

by

All weekly stool samples were examined for campylobacter standard procedures with Campy-Bap medium made with Brucella agar (BBL Microbiology Systems, Cockeysville, Maryland), 5% lysed sheep erythrocytes, and the following antibiotics: vancomycin (10 mg/1), trimethoprim (5 mg/1), polymyxin B (2500 IU/1), amphotericin B (2 mg/1), and cephalothin (15 mg/1).’ Cultures were incubated at 42°C in a CO2-enriched, microaerophilic atmosphere. Plates were examined after 48-72 h and suspect colonies were identified as Campylobacter sp on the basis of bacterial morphology. If the hippurate hydrolysis test was positive, the strain was identified as Cjejuni. All diarrhoeal stool specimens were examined by light microscopy for amoeba and giardia and were cultured for Escherichia coli, Salmonella, Shigella, and Aerornonas. E coli was further characterised for the presence of heat-stablelO and heatlabile" enterotoxins. Stool supematants were also tested by an enzyme-linked immunosorbent assay (ELISA) for the presence of rotavirus antigen.12

Definition of Events A diarrhoeal episode, in children aged over 1 year, was defmed as the presence of at least 1 day with four or more loose motions per day or with one or more loose stools that contained blood. The end of the episode was taken as the 5th day with fewer than three stools per day and the absence of blood. In infants a diarrhoeal episode was defined as any increase in stool frequency or looseness which was of concern to the mother. Campylobacter infection was said to be diarrhoea free when there were at least 5 consecutive symptom-free days before and after the isolation of campylobacter in faeces. Campylobacter infection was said to be symptom-producing whenever a diarrhoeal episode occurred 5 days before or after the faecal isolation of campylobacter. The illness-to-infection ratio was the proportion of symptom-producing campylobacter infections to all campylobacter infections.

Statistical Method Incidence rates were calculated by dividing the number of episodes by the number of child-years of observation. Association between age (as the independent variable) and each of the enteric

Incidence of campylobacter infections at increasing age groups, in a cohort of 179 Mexican children. Illness to infection ratio: 0-5 months, 0-46; 6-11 months, 0-22; 12-23 months, 0-17; 24-35 months, 0-14; 36-47 months, 0-15; 48-59 months, 017; 60-71 months, 0.

infection rates (as the dependent variable) was derived from Pearson’s r correlation index.l3 The age-adjusted relative risk (RR) ratio and its 95 % confidence intervals (95 % CI) were calculated by the maximum likelihood method." Expected numbers of children with different numbers of episodes were calculated from a Poisson distribution, after allowing for age and time of observation. 13

Results There were 125 child-years of observation for the 179 children followed up. 45 children (25%) dropped out of the study before the end because their families moved out of the study area. We were able to collect a weekly stool sample for 84% of all child-weeks of observation and this rate was about the same for all age groups. 90% of the 309 campylobacter strains isolated were C jejuni. 66% of all children had at least one episode of intestinal campylobacter infection during the study period, although only 30% of infected children had symptoms. The overall annual incidence rate of diarrhoeal episodes (irrespective of aetiology) was 2-7 episodes per child, and that for all campylobacter infections (both diarrhoea-free and symptom-producing) was 2-1episodes per child (1-7 episodes per child for diarrhoea-free infections and 0-4 episodes per child for symptom-producing infections). Campylobacter intestinal infections, whether associated with diarrhoea or not, occurred from an early age (see accompanying figure). The annual incidence was 2 episodes per child for the first six months of life, with a peak at 3-5 episodes per child for those aged 12-17 months. Beyond this age the rate of campylobacter infections declined steadily with increasing age, children older than 4 years having less than 1 episode per child-year (r= -078; t,=33, 0-02 > p > 001). The illness-to-infection ratio was highest (50%) during the first 6 months of life—ie, one out of two intestinal infections was associated with diarrhoea; despite a rise in the incidence of campylobacter infections during the third 6 months of life, the illness-to-infection ratio dropped 0-67; t,,, 2-9, 0-02 > p > 0-01) considerably with age (r (figure). Similarly, a significant inverse association was found between age and the incidence rate of symptomproducing and diarrhoea-free infections, and also between age and the mean duration of the diarrhoea-free episodes =

-

=

(table I). The median duration of campylobacter diarrhoea was 3 1 to 29). In diarrhoea-free infections, median duration of excretion was 7 days (range 7-26). 12 out of 52 symptom-producing infections (23%) were followed by

days (range

505 Case-control studies in Australia,ls The Gambia,16 South Africa," India,18 and Bangladesh 59 have consistently shown

TABLE I-CORRELATION BETWEEN AGE AND CAMPYLOBACTER INTESTINAL INFECTIONS

high prevalence of symptom-free campylobacter carriage states, which has raised doubts among some authors as to the pathogenicity of C jejuni in these populations. However, it is clear from our findings that campylobacter is a true pathogen in susceptible individuals. Our data show that very young children were the most likely to become ill after an infection, the ratio of symptom-producing to diarrhoea-free infections being 1:1 among infants under 6 months of age and 1:6 among children aged 3 years, while infections among those aged over 5 years did not cause diarrhoea. It is also noteworthy that from most of the children with campylobacter diarrhoea, campylobacter was the only enteropathogen isolated. The decreasing illness-to-infection ratio with increasing age is also strong evidence that effective natural immunity follows intense early exposure to the organism, as previously suggested.5,6 Through this protective mechanism older children become resistant, not only to disease but also to colonisation by campylobacter. Further evidence of acquired immunity includes the rise in titres of serum and faecal antibodies to different campylobacter antigens after a natural infection 111-23 and the age-related increase in titres of specific serum antibodies to campylobacter, particularly IgA, in children from some developing countries.7,8 Infection in laboratory animals2425 and volunteers26 has also been shown to protect against illness and against colonisation after rechallenge. There may be other explanations for the high rate of diarrhoea-free infections among our children. First, strains of campylobacter may differ in degree of pathogenicity, but this would not explain the clear relation between symptomfree infections and age. Secondly, the high rate of isolation from healthy controls in previous cross-sectional studies could have been partly explained by a prolonged convalescent excretion, which would spuriously increase the point prevalence of infection. However, we have found that campylobacter enteric excretion after a diarrhoeal episode was of short duration and could be clearly differentiated from true symptomless carriage. Symptom-producing early campylobacter infections seemed to protect against subsequent infection, whereas symptom-free infections did not. A possible explanation for this finding could be that some strains lack not only the ability to produce disease but also to induce a protective immune response, with only strains possessing virulence factors, such as adherence, invasiveness, and toxins, being able to induce diarrhoea and immunity. In view of the high frequency of campylobacter infection in developing countries and the morbidity it produces in very young children, the finding that acquired immunity can protect against subsequent infection supports efforts to develop a vaccine against campylobacter enteritis for high-risk

a

NS = Non-significant. TABLE II-FREQUENCY DISTRIBUTION OF CHILDREN INFECTED WITH DIFFERENT NUMBER OF CAMPYLOBACTER INFECTION EPISODES

*Includes diarrhoea-free and symptom-producing episodes. tAccording to a Poisson distribution, after allowing for age and time of observation, stochastic difference between observed and expected values:

=208,p>01).

post-illness intestinal excretion of campylobacter for a median period of 7 days (range 7 to 27). Polymicrobial infections associated with faecal isolation of campylobacter occurred in only 4 out of 52 symptomproducing campylobacter infections (8%) (shigella in 2, and enteropathogenic E coli in the other 2). We assessed whether campylobacter infection early in life could protect against subsequent infections. There was no difference in the risk of having any campylobacter infection (symptom-producing or diarrhoea-free) after 6 months of age between children who had and those who did not have at least one infection during the first 6 months of life (relative

risk=0-77; 95% CI 0-50-1-19). However, those with

a

symptom-producing infection in the first 6 months of life were less likely to have a subsequent campylobacter infection than those with a diarrhoea-free infection early in life (relative risk = 0-14; 95% CI 0-06-0-32). Finally, to examine whether a clustering of campylobacter infections occurred, the frequency distribution of children with different numbers of infectious episodes was compared with the number of children expected from a random distribution. The distributions were not statistically different once age and observation period were allowed for (table II). The same was observed for the diarrhoea-free and for the symptomatic infections. Discussion Our

longitudinal prospective study has confirmed from cross-sectional studies that, in developing countries, campylobacter infection is predominantly an

findings

infection of young children and that the rate of isolation declines with increasing age.Z,5 In our study the peak annual incidence of 35 episodes per child of campylobacter infections (both symptom-producing and diarrhoea-free infections) was found among children aged 12 to 17 months; the incidence declined to 0-6 episodes per child for those

aged 5 years.

populations. We thank Dr William Pickin for his useful comments on this manuscript and Mrs Esther G. Vitervo-Mejia for secretarial assistance. This study was financially supported by grant PCSABNA-021739 from the Consejo Nacional de Ciencia y Tecnologia, Mexico.

Correspondence

should be addressed

to

G. M. R-P.

REFERENCES 1. Blaser

MJ, Reller LB Campylobacter enteritis. N Engl J Med 1981; 305: 1444-52.

506

Review of Books Public Health and Human

Ecology

John M. Last. Norwalk: Appleton and Lange. ISBN 0-838580459. 13.95 (paperback).

1987.

Pp

404.

THIS is a personal overview of issues in public health. It is also about human ecology as seen through the eyes of a committed epidemiologist, and in this respect the title promises more than is revealed. Some of the material is distilled from one of the encyclopaedic genre textbooks that the author, based in Ottawa, has edited for several years. This latest book is definitely slanted more towards thinking than reference. The chapter headings hold few surprises. There are sections on: the scope, goals, and methods of public health; health information and epidemiology; communicable diseases; environmental health; food and nutrition; social and behavioural determinants of health; control of noncommunicable conditions; organisation of public health services; hazards of health care; world health; ethical issues in public health; and the future of health and health services. Only in the last pages do priorities get into the picture. Limiting human population comes out top of the list, with "nothing to excess" not far behind. The intention is that health students and physicians with careers peaking around the year 2000 can get a glimpse of "how the future might unfold"-not an easy challenge, especially since there is a powerful bias towards northern America and the industrialised countries, with only passing references to the health of the have-nots elsewhere. It is difficult to accept the justification given for such an approach, that "many problems differ only in relatively unimportant details between ... Bogota, Brisbane, Beijing, or

Bombay".

This book is good at defining what public health is about, and putting the value of epidemiological analysis into context. It is strong on some of the occupational diseases and

2 Blaser

MJ, Taylor DN, Feldman RA. Epidemiology of Campylobacter jejum infections Epidemiol Rev 1983; 5: 157-76. 3. Programme for Control of Diarrhoeal Diseases. Fifth Programme Report 1984-1985. WHO/CDD/86. 16: 61-63 4. Ruiz-Palacios BR, Bojalil R, Male R, Schuller D, Ramos A. Characterisation of seasonal patterns of enteropathogens in an endemic area. first step for a diarrhea control program Abstracts of the 87th annual meeting of the American Society for Microbiology, Atlanta, Georgia, 1987 350. Huq MI, Struelens MJ, Blaser M, Kibriya AKMG Epidemiologic and clinical features of endemic Campylobacter jejum infection in Bangladesh. J Infect Dis 1983; 148: 292-96. 6 Glass RI, Stoll BJ, Huq MI, Struelens M, Kibriya AKMG. Family studies of Campylobacter jejuni in Bangladesh: Implications for pathogenesis and transmission In Pearson AD, Skirrow MB, Rowe B, Davies JR, Jones DM, eds. Campylobacter II. London. Public Health Laboratory Service. 1983; 141-12. 7. Blaser MJ, Black RE, Duncan DJ, Amer J Campylobacter jejum-specific serum antibodies are elevated in healthy Bangladeshi children. J Clin Microbiol 1985; 21: 5. Glass RI, Stoll BJ,

164-67. 8. Blaser MJ, Taylor DN, Echeverria P. Immune response to Campylobacter jejum in a rural community m Thailand. J Infect Dis 1986, 153: 249-54 9 Blaser MJ, Glass RI, Huq MI, Stoll BJ, Kibriya GM, Alim ARMA. Isolation of Campylobacter fetus subsp jejum from Bangladeshi children J Clin Microbiol 1980; 12: 7454-47. 10. Dean AG, Ching YC, Williams RG, Harden LB. Test of Escherichia coli enterotoxin using infant mice application in a study of diarrhoea in children in Honolulu J Infect Dis 1972; 125: 407-11 11. Guerrant RL, Brunton LL, Schnaitman TC, Rebhun LI, Gilman AG Cyclic adenosine monophosphate and alteration of chinese hamster ovary cell morphology a rapid, sensitive, in vitro assay for the enterotoxins of Vibrio cholera and Escherichia coli Infect Immun 1974; 10: 320-27. 12 Yolken RH, Kim HW, Clem T, et al. Enzyme-linked immunosorbent assay (ELISA) for detection of human reovirus-like agent of infantile gastroenteritis. Lancet 1977; ii: 263-67. 13. Colton T Statistics in medicine Boston Little, Brown, 1974.

the man-made hazards of tobacco, alcohol, and drug abuse. Ethical problems are highlighted by the dilemma of AIDS carriers. On the other hand, it is not a place for the uninitiated to look for ways to calculate risk or standardisation, whose arithmetic is quite correctly, dismissed as tedious. Those concerned with malnutrition, will also be disappointed. The section on food and nutrition is dominated by questions of food quality and consumption that relate mostly to industrial societies. Protein-energy malnutrition gets relegated to a paragraph in which readers are referred to textbooks of nutritional biochemistry. An overall weakness is the comparatively few examples given of turning public health knowledge into programmatic reality. Agreed that nutrition education is desirable: how do you get it to work? There are a few errors, such as the date given for the eradication of smallpox; and some debatable inclusions such as the development of a cholera vaccine in 1896, when we are still spending huge sums in the search for a vaccine that is actually effective. On the whole, a difficult read for students-a book, rather, for those already in public health who have to face up to the uncomfortable questions. Expanded Programme on Immunisation, World Health Organisation, 1211 Geneva 27, Switzerland

NICHOLAS COHEN

Immunology of the Ear Edited by Joel M. Bemstein and Pearay L. Ogra. New York: Raven. 1987. Pp 535.$107.50. ISBN 0-88167270X.

A

GREAT amount

of work has gone into this book both

individually by the many separate authors and by the editors. The publication is opportune at a time when immunology is attracting much interest in otolaryngology, and especially in otology. The co-editors, themselves well respected for their contributions in this area, have successfully brought together many of those at the forefront of research. Well written and well presented, the book is

14. Rothman KJ. Modem epidemiology. Boston Little, Brown, 1986. 15. Berry RJ, Gracey M, Bamford VW. Campylobacter jejuni carriers aboriginal communities Med J Aust 1981; 1: 381.

in

Australian

in the Gambia Trans R Soc Trop Med Hyg 1981; 75: 641-44. 17. Bokkenheusser VD, Richardson NJ, Bryner JH, et al Detection of enteric campylobacteriosis in children. J Clin Microbiol 1979; 9: 227-32 18. Rajan DP, Mathan VI. Prevalence of Campylobacter fetus subsp. jejum in healthy populations in Southern India. J Clin Microbiol 1982; 15: 749-51. 19. Blaser MJ, Duncan DJ. Human serum antibody response to Campylobacter jejum

16.

Billingham JD. Campylobacter enteritis

infection as measured in an enzyme-linked immunosorbent assay. Infect Immun 1984; 44: 292-98 20. Kaldor J, Pritchard H, Serpell A, Metcalf W. Serum antibodies in Campylobacter enteritis. J Clin Microbiol 1983; 18: 1-4. 21. Ruiz Palacios GM, Lopez-Vidal Y, Torres J, Torres N. Serum antibodies to heat-labile enterotoxm of Campylobacter jejuni. J Infect Dis 1985; 152: 413-46.

S, Maki S Serum antibodies reacting with Escherichia coli heat-labile enterotoxin in sera of patients suffering from Campylobacter jejuni infection. FEMS Microbiol Letters 1986, 136: 53-55. 23 Winsor DK, Mathewson JJ, Dupont H. Western blot analysis of intestinal secretory immunoglobulin A response to Campylobacter jejuni antigens in patients with naturally acquired Campylobacter enteritis. Gastroenterology 1986, 90: 1217-22. 24. Ruiz-Palacios GM, Lopez-Vidal Y, Lopez-Vidal AB, Torres J, Rubio S Systemic and local immune response in experimental Campylobacter infection In: Pearson AD, Skirrow MB, Rowe B, Davis JR, Jones DM, eds. Campylobater II. London Public Health Laboratory Service, 1983: 115-16. 22 Honda T, Miwatani T, Mizuno

25. Caldwell

MB, Walker RI, Stewart SD. Development of an adult rabbit model of infection suitable for testing immune response to disease. In. Pearson AD, Skirrow MB, Rowe B, Davis JR, Jones DM, eds. Campylobacter II. London: Public Health Laboratory Service, 1983: 114 Black RE, Levine KH, Brown KH, Clements ML, Lopez de Roman G. Immunity of Campylobacter jejuni in man In: Pearson AD, Skirrow MB, Lior H, Rowe B, eds Campylobacter III. London Public Health Laboratory Service, 1985 129

Campylobacter

26.