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PERSON-TO-PERSON TRANSMISSION OF CAMPYLOBACTER PYLORI
680 Immunisation with
paternal
cells remains
a
safe and effective
treatment for most women with recurrent spontaneous miscarriage.
We thank those who have referred patients and the patients themselves. This work is supported by the Medical Research Council, the Joint Standing Research Committee and Save the Baby Fund of St Mary’s Hospital, and
Reprim Research.
J. F. MOWBRAY J. L. UNDERWOOD
Harris Birthright Centre for Research into Early Pregnancy, St Mary’s Hospital Medical School, London W2 1PG
1.
M. MICHEL P. B. FORBES R. W. BEARD
31
879
1302
1726
ABSORBANCE (405 nm)
Liddell H, Reginald PW, Underwood JL, Beard RW. Controlled trial of treatment of recurrent spontaneous abortion with paternal cells. Lancet 1985; i: 941-43. 2. Gill TJ, MacPherson TA, Ho HN, et al. Immunological and genetic factors affecting
Mowbray JF, Gibbings C,
implantation and development in rat and human. In: Gill TJ, Wegmann TE, eds. Immunoregulation and fetal survival. Oxford and New York: Oxford University Press, 1986: 137-55. 3. MacFarlane A, Mugford M, eds. Birth counts: Statistics of pregnancy and childbirth. London: HM Stationery Office, 1984: 188-89. 4. Beer AE, Quebbeman JF, Hamazaki Y, Semprini AE. Immunotherapy for recurrent spontaneous abortion. In Gill TJ, Wegmann TE, eds. Proceedings of Second Banff Conference on Reproductive Immunology. Oxford: Oxford University Press, 1986: 286-99. 5. Gill TJ. Genetic factors in fetal losses. Am J Reprod Immunol Microbiol (in press). 6. Mowbray JF. Genetic and immunological factors in human recurrent abortions. Am Reprod Immunol Microbiol (in press).
455
J
PERSON-TO-PERSON TRANSMISSION OF CAMPYLOBACTER PYLORI
SIR,--One of the gaps in the understanding of Campylobacter pylori infection is its means of transmission. We have looked for C pylori antibody in serum from 98 patients in an institution for the mentally retarded, such patients being a known high-risk group for person-to-person spread of pathogens via faecal-oral and/or respiratory droplet routes. As controls we used blood donors and children being investigated for other reasons and we also measured, in the retarded patients’ sera, antibody to C jejuni, a common diarrhoeal agent in Australia. Prof R. A. Hawkes and Prof C. R. Boughton provided sera collected by the Red Cross from blood donors routinely seen at eleven collection centres in New South Wales. They also provided sera from inmates of a New South Wales residential institution for the mentally retarded, which housed males and females of all ages. These latter sera had been collected in December, 1971, during a study on hepatitis. Dr P. W. Robertson (Prince of Wales Hospital, Kensington, NSW) provided sera from children being routinely antibody screened or for complaints not related to gastrointestinal upsets or Guillain-Barre syndrome. The children were matched by age with children from the residential institution. We tested for C pylori and C jejuni antibodies by ELISA (details available from J. B.). The level of serum IgG considered positive was set such that the cross-reactivity in the ELISAs for these two organisms would not result in false positives. The age distribution of
(X 1000) Fig 2-Distribution of absorbances in 767 blood donors ELISA tested for anti-C pylori IgG. blood donors with significant (1000 units or more) anti-C pylori IgG levels is shown in fig 1 A. The increase in anti-C pylori in older adults contrasts with the distribution of antibody to C jejuni in the same people (fig IB). There was a bimodal distribution of anti-C pylori IgG levels (fig 2) suggesting that donors with no or only limited past exposure to C pylori have antibody levels below 500 ELISA units while those with active infection have levels of 1000 units or more. The sera of younger blood donors did not form the lower peak and the older blood donors’ the higher peak; rather, in the younger age group there is a proportion of persons with high anti-C pylori IgG levels, and the relative size of this actively infected group increases sharply with age (data not shown). C pylori IgG antibody levels similar to that used here as a cut-off (geometric mean titre 2540) have been associated with active gastritis and C pylori infection.1,2 The bimodal distribution of antibody levels in blood donors suggests a distinct population of people actively infected with C pylori. About 20 % of normal adults may be infected. In a limited study of deaths from causes not related to gastrointestinal disease 19% of whites had active gastritis and C pylori in the stomach.3 The rates of high serum anti-C pylori carriage were significantly greater in the institutionalised residents than in blood donors at all ages (table I). There was also a significantly higher rate of anti-C jejuni IgG in the mentally retarded. Table II shows the rate of seropositivity for C pylori antibody related to both duration of residence at the institution, and to age. These two variables are confounded; however, the effect of longer residence is large enough to be statistically significant in itself. Jones, Kaldor, and colleagues1,4 have suggested that C pylori is acquired throughout life-ie, the older one is, the more likely one is to come in contact with the organism. Seroconversion in a population sporadically exposed to an infectious agent usually happens in childhood and adolescence (as with C jejuni in our study). For most infections to occur after age 40 or so is an unusual
TABLE I-RATES OF SERUM ANTI-C PYLORI AND ANTI-C
CARRIAGE* IN NORMAL
POPULATION! AND
JEJUNI
IN
MENTALLY RETARDED PATIENTS IN NEW SOUTH WALES
28-32
33-37
38-42
AGE GROUP
43-47
48-52
53-5/ 58-65
(YEARS)
Fig 1—Age distribution of seropositive donors.
Upper (A): anti-C pylori. Lower (B): anti-C jejuni.
*Positive = absorbance 10 for C pylori and 07 for C jejuni antibody. t767 NSW blood donors + 31 children seen at Prince of Wales Hospital.
681 TABLE II-DISTRIBUTION OF C PYLORI ANTIBODY-POSITIVE RETARDATES ACCORDING TO AGE AND DURATION OF
TABLE 1-HISTOLOGICAL FINDINGS IN INDEX PATIENTS
INSTITUTIONALISATION
seroconversion pattern and could be very important to our understanding of the epidemiology of C pylori infection and of the. disease itself. Our data are consistent with the idea that in the normal stomach the conditions are usually suboptimal for colonisation, but as one gets older the local environment of the stomach changes such that C pylori can more easily establish infection. The data on the mentally retarded in an institution are also important. These sera are old but they have been carefully stored.s Transmission of C pylori infection has not been reported, apart from transmission via a gastroscope.6 C pylori has not been isolated outside the human gastric mucosa and no natural animal carrier has been found. Seropositivity for C pylori was consistently more frequent in the mentally retarded inpatients than in groups of similar age in the normal population. This strongly suggests person-to-person transmission, a view supported by the increased rates seen in longer term residents. One possibility is transmission by intimate contact; this happens in such institutions and should be considered in the spread of C pylori infection. We thank R. A. Hawkes for access to his and C. R. Boughton’s serum stores, S. L. Hazell and P. W. Robertson for providing sera and for useful discussion, A. E. Stark for statistical help, and K. R. Redell for computer assistance.
School of Microbiology, University of New South Wales, Kensington, NSW 2033, Australia
JOHN BERKOWICZ
available; NS=no significant abnormality, and =negative, + - equivocal, + = few, + + moderate, and + + + large numbers of C pylori or, on histology, cells (plasma cells, mononuclear cells, polymorphs, or lymphocytes).
NA=not
1000.
ADRIAN LEE
Jones DM, Eldridge J, Fox AJ, Sethii P, Whorwell PJ. Antibody
the gastric campylobacter-like organism ("Campylobacter pyloridis"): clinical correlations and distribution in the normal population. J Med Microbiol 1986; 22: 57-62. 2. Booth L, Holdstock G, MacBride H, et al. Clinical importance of Campylobacter pyloridis and associated serum IgG and IgA antibody responses in patients undergoing upper gastrointestinal endoscopy. J Clin Pathol 1986; 39: 215-19. 3. Morris A. Campylobacter pyloridis gastritis. Aust Microbiol 1987; 8: 190. 4. Kaldor J, Tee W, Nicolapolous C, et al. Immunoblot confirmation of immune response to Campylobacter pyloridis in patients with duodenal ulcers. Med JAust 1986; 145: 133-35. 5. Boughton CR, Hawkes RA, Schroeter DR, Harlor JA. The epidemiology of hepatitis B in a residential institution for the mentally retarded Aust NZ J Med 1976; 6: 521-29. 6. Ramsey EJ, Carey AV, Peterson WL, et al. Epidemic gastritis with hypochlorhydria. Gastroenterology 1979; 76: 1449-57.
SIR,-Although Campylobacter pylori is now established as a of most cases of active chronic gastritis,l little is known about the source and spread of this organism. To increase our cause
of the transmission of C pylori we looked for antibodies in the direct family contacts of 4 children (aged 7½, 82, 14, and 16 years) with proven C pylori infection who presented to the Prince of Wales Children’s Hospital, Sydney. We also tested sera from 767 blood donors and from 31 children being screened for antibodies not related to gastrointestinal illness for IgG antibody to C pylori.. All four children reported abdominal pain as their major symptom and in the two older children epigastric burning, reflux, burping, periodic nausea, epigastric distension, flatulence, and halitosis were also reported. Gastric biopsies on all 4 children were positive in the microtitre urease testHistological findings were consistent with previous reports of C pylori induced gastritis
(table i).
II-IgG ABSORBANCE LEVELS
IN PATIENTS AND DIRECT
FAMILY MEMBERS
to
ANTIBODY TO CAMPYLOBACTER PYLORI IN FAMILIES OF INDEX CHILDREN WITH GASTROINTESTINAL ILLNESS DUE TO C PYLORI
understanding
=
C pylori was found in the oesophagus of patient 3. This child with spina bifida and hydrocephalus had Barrett’s oesophagus (acidsecreting gastric mucosa on biopsy) and chronic reflux oesophagitis. Given the association between C pylori and peptic ulceration, clinicians should be encouraged to look for C pylori in cases of oesophagitis and oesophageal ulceration. After endoscopy and before treatment serum was obtained from the 4 patients and their direct family contacts. The 14 family contacts were consanguineous and aged 6 months to 73 years (mean 32 years). IgG and IgM levels were measured by ELISA with sonicated whole cells of C pylori strains NTCC 11639 and P.30 as antigens. For IgG an absorbance above 1-0 was considered to be evidence of an active infection, equivalent to a mean geometric titre of 2540. For IgM an absorbance cut-off 0-650 was considered to be evidence of a recent acute infection, equivalent to a mean titre of TABLE
1.
-
=
*Baby aged 6 months.
All four patients had high levels of IgG antibody to C pylori, and among family contacts high levels of IgG antibody were also found (table n). 9 of the 14 family contacts had IgG antibodies to C pylori. This, however, is a conservative estimate since the absorbance cut-off was selected to give a specificity approaching 100 %, at the expense of some sensitivity. The father in family 2 (IgG absorbance 0-940) is probably infected with C pylori. The carriage rate of IgG antibody to C pylori in the blood donor controls was 20%. The frequency of antibody carriage in family contacts (64%) was significantly greater than that in 166 age-matched controls (13%) (p<0’001). These results contrast with those of Jones et al3 who reported no increased frequency of antibodies in relatives of adult index patients from whom C pylori had been cultured on gastric specimens. In our series no patient or family contact had an abnormal IgM level. A genetic predisposition to infection with C pylori within families seems unlikely, given the widespread distribution of this infection in the community. Direct transmission of C pylori within family contacts seems the most likely interpretation. When one member of the family is carrying large numbers of C pylori in the stomach these may be spread by respiratory droplets or the faecal/oral route. A
paternal
cells remains
a
safe and effective
treatment for most women with recurrent spontaneous miscarriage.
We thank those who have referred patients and the patients themselves. This work is supported by the Medical Research Council, the Joint Standing Research Committee and Save the Baby Fund of St Mary’s Hospital, and
Reprim Research.
J. F. MOWBRAY J. L. UNDERWOOD
Harris Birthright Centre for Research into Early Pregnancy, St Mary’s Hospital Medical School, London W2 1PG
1.
M. MICHEL P. B. FORBES R. W. BEARD
31
879
1302
1726
ABSORBANCE (405 nm)
Liddell H, Reginald PW, Underwood JL, Beard RW. Controlled trial of treatment of recurrent spontaneous abortion with paternal cells. Lancet 1985; i: 941-43. 2. Gill TJ, MacPherson TA, Ho HN, et al. Immunological and genetic factors affecting
Mowbray JF, Gibbings C,
implantation and development in rat and human. In: Gill TJ, Wegmann TE, eds. Immunoregulation and fetal survival. Oxford and New York: Oxford University Press, 1986: 137-55. 3. MacFarlane A, Mugford M, eds. Birth counts: Statistics of pregnancy and childbirth. London: HM Stationery Office, 1984: 188-89. 4. Beer AE, Quebbeman JF, Hamazaki Y, Semprini AE. Immunotherapy for recurrent spontaneous abortion. In Gill TJ, Wegmann TE, eds. Proceedings of Second Banff Conference on Reproductive Immunology. Oxford: Oxford University Press, 1986: 286-99. 5. Gill TJ. Genetic factors in fetal losses. Am J Reprod Immunol Microbiol (in press). 6. Mowbray JF. Genetic and immunological factors in human recurrent abortions. Am Reprod Immunol Microbiol (in press).
455
J
PERSON-TO-PERSON TRANSMISSION OF CAMPYLOBACTER PYLORI
SIR,--One of the gaps in the understanding of Campylobacter pylori infection is its means of transmission. We have looked for C pylori antibody in serum from 98 patients in an institution for the mentally retarded, such patients being a known high-risk group for person-to-person spread of pathogens via faecal-oral and/or respiratory droplet routes. As controls we used blood donors and children being investigated for other reasons and we also measured, in the retarded patients’ sera, antibody to C jejuni, a common diarrhoeal agent in Australia. Prof R. A. Hawkes and Prof C. R. Boughton provided sera collected by the Red Cross from blood donors routinely seen at eleven collection centres in New South Wales. They also provided sera from inmates of a New South Wales residential institution for the mentally retarded, which housed males and females of all ages. These latter sera had been collected in December, 1971, during a study on hepatitis. Dr P. W. Robertson (Prince of Wales Hospital, Kensington, NSW) provided sera from children being routinely antibody screened or for complaints not related to gastrointestinal upsets or Guillain-Barre syndrome. The children were matched by age with children from the residential institution. We tested for C pylori and C jejuni antibodies by ELISA (details available from J. B.). The level of serum IgG considered positive was set such that the cross-reactivity in the ELISAs for these two organisms would not result in false positives. The age distribution of
(X 1000) Fig 2-Distribution of absorbances in 767 blood donors ELISA tested for anti-C pylori IgG. blood donors with significant (1000 units or more) anti-C pylori IgG levels is shown in fig 1 A. The increase in anti-C pylori in older adults contrasts with the distribution of antibody to C jejuni in the same people (fig IB). There was a bimodal distribution of anti-C pylori IgG levels (fig 2) suggesting that donors with no or only limited past exposure to C pylori have antibody levels below 500 ELISA units while those with active infection have levels of 1000 units or more. The sera of younger blood donors did not form the lower peak and the older blood donors’ the higher peak; rather, in the younger age group there is a proportion of persons with high anti-C pylori IgG levels, and the relative size of this actively infected group increases sharply with age (data not shown). C pylori IgG antibody levels similar to that used here as a cut-off (geometric mean titre 2540) have been associated with active gastritis and C pylori infection.1,2 The bimodal distribution of antibody levels in blood donors suggests a distinct population of people actively infected with C pylori. About 20 % of normal adults may be infected. In a limited study of deaths from causes not related to gastrointestinal disease 19% of whites had active gastritis and C pylori in the stomach.3 The rates of high serum anti-C pylori carriage were significantly greater in the institutionalised residents than in blood donors at all ages (table I). There was also a significantly higher rate of anti-C jejuni IgG in the mentally retarded. Table II shows the rate of seropositivity for C pylori antibody related to both duration of residence at the institution, and to age. These two variables are confounded; however, the effect of longer residence is large enough to be statistically significant in itself. Jones, Kaldor, and colleagues1,4 have suggested that C pylori is acquired throughout life-ie, the older one is, the more likely one is to come in contact with the organism. Seroconversion in a population sporadically exposed to an infectious agent usually happens in childhood and adolescence (as with C jejuni in our study). For most infections to occur after age 40 or so is an unusual
TABLE I-RATES OF SERUM ANTI-C PYLORI AND ANTI-C
CARRIAGE* IN NORMAL
POPULATION! AND
JEJUNI
IN
MENTALLY RETARDED PATIENTS IN NEW SOUTH WALES
28-32
33-37
38-42
AGE GROUP
43-47
48-52
53-5/ 58-65
(YEARS)
Fig 1—Age distribution of seropositive donors.
Upper (A): anti-C pylori. Lower (B): anti-C jejuni.
*Positive = absorbance 10 for C pylori and 07 for C jejuni antibody. t767 NSW blood donors + 31 children seen at Prince of Wales Hospital.
681 TABLE II-DISTRIBUTION OF C PYLORI ANTIBODY-POSITIVE RETARDATES ACCORDING TO AGE AND DURATION OF
TABLE 1-HISTOLOGICAL FINDINGS IN INDEX PATIENTS
INSTITUTIONALISATION
seroconversion pattern and could be very important to our understanding of the epidemiology of C pylori infection and of the. disease itself. Our data are consistent with the idea that in the normal stomach the conditions are usually suboptimal for colonisation, but as one gets older the local environment of the stomach changes such that C pylori can more easily establish infection. The data on the mentally retarded in an institution are also important. These sera are old but they have been carefully stored.s Transmission of C pylori infection has not been reported, apart from transmission via a gastroscope.6 C pylori has not been isolated outside the human gastric mucosa and no natural animal carrier has been found. Seropositivity for C pylori was consistently more frequent in the mentally retarded inpatients than in groups of similar age in the normal population. This strongly suggests person-to-person transmission, a view supported by the increased rates seen in longer term residents. One possibility is transmission by intimate contact; this happens in such institutions and should be considered in the spread of C pylori infection. We thank R. A. Hawkes for access to his and C. R. Boughton’s serum stores, S. L. Hazell and P. W. Robertson for providing sera and for useful discussion, A. E. Stark for statistical help, and K. R. Redell for computer assistance.
School of Microbiology, University of New South Wales, Kensington, NSW 2033, Australia
JOHN BERKOWICZ
available; NS=no significant abnormality, and =negative, + - equivocal, + = few, + + moderate, and + + + large numbers of C pylori or, on histology, cells (plasma cells, mononuclear cells, polymorphs, or lymphocytes).
NA=not
1000.
ADRIAN LEE
Jones DM, Eldridge J, Fox AJ, Sethii P, Whorwell PJ. Antibody
the gastric campylobacter-like organism ("Campylobacter pyloridis"): clinical correlations and distribution in the normal population. J Med Microbiol 1986; 22: 57-62. 2. Booth L, Holdstock G, MacBride H, et al. Clinical importance of Campylobacter pyloridis and associated serum IgG and IgA antibody responses in patients undergoing upper gastrointestinal endoscopy. J Clin Pathol 1986; 39: 215-19. 3. Morris A. Campylobacter pyloridis gastritis. Aust Microbiol 1987; 8: 190. 4. Kaldor J, Tee W, Nicolapolous C, et al. Immunoblot confirmation of immune response to Campylobacter pyloridis in patients with duodenal ulcers. Med JAust 1986; 145: 133-35. 5. Boughton CR, Hawkes RA, Schroeter DR, Harlor JA. The epidemiology of hepatitis B in a residential institution for the mentally retarded Aust NZ J Med 1976; 6: 521-29. 6. Ramsey EJ, Carey AV, Peterson WL, et al. Epidemic gastritis with hypochlorhydria. Gastroenterology 1979; 76: 1449-57.
SIR,-Although Campylobacter pylori is now established as a of most cases of active chronic gastritis,l little is known about the source and spread of this organism. To increase our cause
of the transmission of C pylori we looked for antibodies in the direct family contacts of 4 children (aged 7½, 82, 14, and 16 years) with proven C pylori infection who presented to the Prince of Wales Children’s Hospital, Sydney. We also tested sera from 767 blood donors and from 31 children being screened for antibodies not related to gastrointestinal illness for IgG antibody to C pylori.. All four children reported abdominal pain as their major symptom and in the two older children epigastric burning, reflux, burping, periodic nausea, epigastric distension, flatulence, and halitosis were also reported. Gastric biopsies on all 4 children were positive in the microtitre urease testHistological findings were consistent with previous reports of C pylori induced gastritis
(table i).
II-IgG ABSORBANCE LEVELS
IN PATIENTS AND DIRECT
FAMILY MEMBERS
to
ANTIBODY TO CAMPYLOBACTER PYLORI IN FAMILIES OF INDEX CHILDREN WITH GASTROINTESTINAL ILLNESS DUE TO C PYLORI
understanding
=
C pylori was found in the oesophagus of patient 3. This child with spina bifida and hydrocephalus had Barrett’s oesophagus (acidsecreting gastric mucosa on biopsy) and chronic reflux oesophagitis. Given the association between C pylori and peptic ulceration, clinicians should be encouraged to look for C pylori in cases of oesophagitis and oesophageal ulceration. After endoscopy and before treatment serum was obtained from the 4 patients and their direct family contacts. The 14 family contacts were consanguineous and aged 6 months to 73 years (mean 32 years). IgG and IgM levels were measured by ELISA with sonicated whole cells of C pylori strains NTCC 11639 and P.30 as antigens. For IgG an absorbance above 1-0 was considered to be evidence of an active infection, equivalent to a mean geometric titre of 2540. For IgM an absorbance cut-off 0-650 was considered to be evidence of a recent acute infection, equivalent to a mean titre of TABLE
1.
-
=
*Baby aged 6 months.
All four patients had high levels of IgG antibody to C pylori, and among family contacts high levels of IgG antibody were also found (table n). 9 of the 14 family contacts had IgG antibodies to C pylori. This, however, is a conservative estimate since the absorbance cut-off was selected to give a specificity approaching 100 %, at the expense of some sensitivity. The father in family 2 (IgG absorbance 0-940) is probably infected with C pylori. The carriage rate of IgG antibody to C pylori in the blood donor controls was 20%. The frequency of antibody carriage in family contacts (64%) was significantly greater than that in 166 age-matched controls (13%) (p<0’001). These results contrast with those of Jones et al3 who reported no increased frequency of antibodies in relatives of adult index patients from whom C pylori had been cultured on gastric specimens. In our series no patient or family contact had an abnormal IgM level. A genetic predisposition to infection with C pylori within families seems unlikely, given the widespread distribution of this infection in the community. Direct transmission of C pylori within family contacts seems the most likely interpretation. When one member of the family is carrying large numbers of C pylori in the stomach these may be spread by respiratory droplets or the faecal/oral route. A