1
394 More seriously, a study of 1018 Italian healthy blood donors showed that although the prevalence of IgG Hpylori antibodies rose from 17% at age 18-25 to 55% at age 46-55, a reverse trend was seen for H pylori IgM antibodies, which fell from 64% at age 18-25 to 33% at age 56--65.2 This study indicates that IgM measurement is the only reliable blood test for current H pylori infection and that IgG testing often merely provides a historical record. All patients over 45 with persistent new dyspepsia and all those with dysphagia should be investigated quickly either with endoscopy or with barium radiology. In adults under this age serious diagnoses are less common, but everyone with persistent dyspepsia deserves investigation before any attempt at therapy that will interfere with test results and may cause long-term therapeutic confusion. The best way to do this remains endoscopy. It is misleading to suggest that the generally available IgG antibody test for H pylori will assist in accurate diagnosis of symptoms since this test needs further refinement.3 IgM measurement or urea breath testing look much more promising. General Hospital, Bishop Auckland County Durham DL14 6AD, UK M. C. BATESON 1. Meyer B, Werth B, Beglinger C, et al. Helicobacter pylori infection in healthy people: a dynamic process? Gut 1991; 32: 347-50. 2. Vaira D, Miglioli M, Holton J, et al. Prevalence of IgG, IgA, IgM to Helicobacter pylori in 1018 blood donors. Gut 1991; 32: A564. 3. Hirschl AM, Rotter ML. Serodiagnosis of Helicobacter pylori infections: suitability of various antigen preparations. In: Malfertheiner P, Ditschuneit P, eds. Helicobacter pylori, gastritis and peptic ulcer. Berlin: Springer-Verlag, 1991; 141-46. Sir disagree with Dr Sobala and colleagues’ conclusion that if their screening test had been applied 23-3% of the endoscopies would have been saved. At best, only 18-3% of the endoscopic workload would have been saved if their in-house ELISA had been used because they fail to take into account the 5% false-positive rate (the group that also requires diagnostic endoscopy). On the other hand, if the commercial ELISA kit (Porton Cambridge, UK) had been used, only 10-3% of the endoscopies would have been saved. My experience with this commercial kit has been less satisfactory (sensitivity 82%, specificity 83%).1 Therefore, depending on the ELISA system used the net reduction on the number of unnecessary endoscopies may not be as much as suggested. Furthermore, I believe the high sensitivity of Sobala and colleagues’ in-house ELISA is overrated. The sensitivity of any test is usually calculated by the number of true positives (nominator) divided by the total number of patients with the condition (the denominator). Very frequently, insensitive tests such as microbiological culture and/or histology have been regarded as the gold standards and, hence, have been used as the denominator to derive the sensitivity of the test used. It is well known that microbiological culture yields low positive results and therefore has poor sensitivity.2 Moreover, histological tests also underestimate the true prevalence of Helicobacter pylori infection because of sampling errors. These pitfalls therefore underscore the unreliability of these tests, either alone or in conjunction, as the denominator to calculate the true sensitivity of the evaluated test. Cost saving has indeed become the prime concern of most administrators and clinicians in National Health Service hospitals. The strategy Sobala et al propose-not to endoscope young ( < 45 years) dyspeptic patients with negative serological tests for H pylori and furthermore to redirect the resources where they are much needed-is certainly attractive. However, before such practice is adopted I recommend that we should be equipped first of all with a truly highly sensitive and specific serological test, such as that reported by Evans et all (sensitivity 98.7% and specificity 100%) to help us to make the correct clinical decision. Medical Research Centre, City Hospital, Edward’s Lane, Nottingham NG5 1 PB, UK C. K. CHING 1. Ching CK, Thompson S, Buxton C, et al. Evaluation of the new Helico-G ELISA for serological diagnosis of Helicobacter pylori infection. Gut 1991; 32: A570. 2. Glupczynski Y, Burette A. Drug therapy of Helicobacter pylori infection: problems and pitfalls. Am J Gastroenterol 1990; 85: 1545-51. 3 Graham DY, Borsch GMA. The who’s and when’s of therapy for Helicobacter pylori. Am J Gastroenterol 1990; 85: 1552-55. 4. Evans DJ, Evans DG, Graham DY, et al. A sensitive and specific serologic test for detection of Campylobacter pylori infection. Gastroenterology 1989; 96: 1004-08. SiR,&mdash;We agree with Dr Sobala and colleagues’ conclusion that screening for Helicobacter pylori by serological detection of IgG antibodies would remove the need for endoscopy in certain cases, and, therefore, would greatly reduce the workload of the endoscopy department. They do not refer to a similar earlier proposal by our group. In this respect, we would raise some points. Sobala et al report high sensitivity and specificity values for both their in-house and commercial assay. If serological tests are used in screening and are the basis for decisions about additional investigations, predictive values would have to be provided. To be of use the test should have, at a certain cut-off point, a positive or negative predictive value of 100%. Since Sobala et al propose that endoscopy should be done if the test is positive, a cut-off value with a negative predictive value of 100% would be advisable. 6 of 192 peptic ulcers in their histology group would have been missed by their strategy. It is tempting to assume that these patients would be diagnosed correctly if a cut-off with a negative predictive value of 100% is used. Sobala and colleagues introduce age as a selection criterion in their screening strategy. One of the main reasons for endoscopy in dyspeptics is to rule out upper gastrointestinal malignant disease. We believe that it is not important if concomitant peptic ulcer disease is missed in helicobacter gastritis since anti-helicobacter treatment also provides effective anti-ulcer treatment. We therefore propose endoscopy in patients with negative serological tests. However, such a strategy implies that patients with non-H pylori-related diseases, of which reflux oesophagitis is the most important, should be seronegative. Unfortunately this is not so, as Sobala et al show in table I. Many patients will probably have coincidental helicobacter gastritis and can be regarded as seropositive. A drawback to the omission of endoscopy irrespective of the serological test results is that a substantial number of patients with reflux oesophagitis are missed and possibly receive the wrong treatment. The diagnosis of gastro-oesophageal reflux disease cannot be diagnosed with certainty from the medical history, and hence endoscopy remains inevitable in suspected reflux disease. Another difficulty is non-ulcer dyspepsia. We assumed that patients with non-ulcer dyspepsia and H pylori infection needed treatment. Although there is doubt about the necessity of treating H pylori infection in these patients, Sobala and colleagues proposal is probably the preferred screening strategy. Sobala et al use two ELISAs. Discrepancies in the test results were seen in 14-6% of results. We too have found a large discrepancy (41-9%) with seven ELISAs (unpublished). This lack of agreement could be because commercial antigens are isolated from locally available strains of H pylori. Since several serotypes of H pylori are observed, a patient infected with a serotype common in one country would probably elicit antibodies that do not react, or slightly react, with antigens from a serotype common in another country. The commercial assay in Sobala et al’s report uses antigens from strains common in the UK, whereas we used assays from manufacturers from different countries, and discrepancies are bound to arise. Departments of Internal Medicine, Pathology, and Microbiology, University Hospital Maastricht, 6202 BX Maastricht, Netherlands R. J. L. F. LOFFELD J. W. ARENDS E. STOBBERINGH 1. Loffeld RJLF, Stobberingh E, Flendrig JA, van Spreeuwel JP, Arends JW. Diagnostic value of an immunoassay to detect anti Campylobacter pylori antibodies in non-ulcer dyspepsia. Lancet 1989; i: 1182-85. CORRECTION Influence of candoxatril on plasma brain natriuretic peptide in heart failure.-In this letter by Dr Lang and colleagues (July 27, p 255) the penultimate sentence of paragraph two should have read "Crossreactivity of the hBNP antibody with human ANP with this assay was 0%. The intrasubject coefficient of variability was 7% for samples from patients with chronic heart failure".

CORRECTION

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394

More seriously, a study of 1018 Italian healthy blood donorsshowed that although the prevalence of IgG Hpylori antibodies rosefrom 17% at age 18-25 to 55% at age 46-55, a reverse trend wasseen for H pylori IgM antibodies, which fell from 64% at age 18-25to 33% at age 56--65.2 This study indicates that IgM measurementis the only reliable blood test for current H pylori infection and thatIgG testing often merely provides a historical record.

All patients over 45 with persistent new dyspepsia and all thosewith dysphagia should be investigated quickly either with

endoscopy or with barium radiology. In adults under this ageserious diagnoses are less common, but everyone with persistentdyspepsia deserves investigation before any attempt at therapy thatwill interfere with test results and may cause long-term therapeuticconfusion. The best way to do this remains endoscopy. It is

misleading to suggest that the generally available IgG antibody testfor H pylori will assist in accurate diagnosis of symptoms since thistest needs further refinement.3 IgM measurement or urea breathtesting look much more promising.General Hospital,Bishop AucklandCounty Durham DL14 6AD, UK M. C. BATESON

1. Meyer B, Werth B, Beglinger C, et al. Helicobacter pylori infection in healthy people: adynamic process? Gut 1991; 32: 347-50.

2. Vaira D, Miglioli M, Holton J, et al. Prevalence of IgG, IgA, IgM to Helicobacter pyloriin 1018 blood donors. Gut 1991; 32: A564.

3. Hirschl AM, Rotter ML. Serodiagnosis of Helicobacter pylori infections: suitability ofvarious antigen preparations. In: Malfertheiner P, Ditschuneit P, eds. Helicobacterpylori, gastritis and peptic ulcer. Berlin: Springer-Verlag, 1991; 141-46.

Sir disagree with Dr Sobala and colleagues’ conclusion thatif their screening test had been applied 23-3% of the endoscopieswould have been saved. At best, only 18-3% of the endoscopicworkload would have been saved if their in-house ELISA had beenused because they fail to take into account the 5% false-positive rate(the group that also requires diagnostic endoscopy). On the otherhand, if the commercial ELISA kit (Porton Cambridge, UK) hadbeen used, only 10-3% of the endoscopies would have been saved.My experience with this commercial kit has been less satisfactory(sensitivity 82%, specificity 83%).1 Therefore, depending on theELISA system used the net reduction on the number of

unnecessary endoscopies may not be as much as suggested.Furthermore, I believe the high sensitivity of Sobala and

colleagues’ in-house ELISA is overrated. The sensitivity of any testis usually calculated by the number of true positives (nominator)divided by the total number of patients with the condition (thedenominator). Very frequently, insensitive tests such as

microbiological culture and/or histology have been regarded as thegold standards and, hence, have been used as the denominator toderive the sensitivity of the test used. It is well known that

microbiological culture yields low positive results and therefore haspoor sensitivity.2 Moreover, histological tests also underestimatethe true prevalence of Helicobacter pylori infection because ofsampling errors. These pitfalls therefore underscore the

unreliability of these tests, either alone or in conjunction, as thedenominator to calculate the true sensitivity of the evaluated test.

Cost saving has indeed become the prime concern of mostadministrators and clinicians in National Health Service hospitals.The strategy Sobala et al propose-not to endoscope young ( < 45

years) dyspeptic patients with negative serological tests for H pyloriand furthermore to redirect the resources where they are muchneeded-is certainly attractive. However, before such practice isadopted I recommend that we should be equipped first of all with atruly highly sensitive and specific serological test, such as thatreported by Evans et all (sensitivity 98.7% and specificity 100%) tohelp us to make the correct clinical decision.Medical Research Centre,City Hospital, Edward’s Lane,Nottingham NG5 1 PB, UK C. K. CHING

1. Ching CK, Thompson S, Buxton C, et al. Evaluation of the new Helico-G ELISA forserological diagnosis of Helicobacter pylori infection. Gut 1991; 32: A570.

2. Glupczynski Y, Burette A. Drug therapy of Helicobacter pylori infection: problems andpitfalls. Am J Gastroenterol 1990; 85: 1545-51.

3 Graham DY, Borsch GMA. The who’s and when’s of therapy for Helicobacter pylori.Am J Gastroenterol 1990; 85: 1552-55.

4. Evans DJ, Evans DG, Graham DY, et al. A sensitive and specific serologic test fordetection of Campylobacter pylori infection. Gastroenterology 1989; 96: 1004-08.

SiR,&mdash;We agree with Dr Sobala and colleagues’ conclusion thatscreening for Helicobacter pylori by serological detection of IgGantibodies would remove the need for endoscopy in certain cases,and, therefore, would greatly reduce the workload of the endoscopydepartment. They do not refer to a similar earlier proposal by ourgroup. In this respect, we would raise some points.

Sobala et al report high sensitivity and specificity values for boththeir in-house and commercial assay. If serological tests are used inscreening and are the basis for decisions about additional

investigations, predictive values would have to be provided. To beof use the test should have, at a certain cut-off point, a positive ornegative predictive value of 100%. Since Sobala et al propose thatendoscopy should be done if the test is positive, a cut-off value witha negative predictive value of 100% would be advisable. 6 of 192peptic ulcers in their histology group would have been missed bytheir strategy. It is tempting to assume that these patients would bediagnosed correctly if a cut-off with a negative predictive value of100% is used.

Sobala and colleagues introduce age as a selection criterion intheir screening strategy. One of the main reasons for endoscopy indyspeptics is to rule out upper gastrointestinal malignant disease.We believe that it is not important if concomitant peptic ulcerdisease is missed in helicobacter gastritis since anti-helicobactertreatment also provides effective anti-ulcer treatment. We thereforepropose endoscopy in patients with negative serological tests.

However, such a strategy implies that patients with non-H

pylori-related diseases, of which reflux oesophagitis is the most

important, should be seronegative. Unfortunately this is not so, asSobala et al show in table I. Many patients will probably havecoincidental helicobacter gastritis and can be regarded as

seropositive. A drawback to the omission of endoscopy irrespectiveof the serological test results is that a substantial number of patientswith reflux oesophagitis are missed and possibly receive the wrongtreatment. The diagnosis of gastro-oesophageal reflux diseasecannot be diagnosed with certainty from the medical history, andhence endoscopy remains inevitable in suspected reflux disease.

Another difficulty is non-ulcer dyspepsia. We assumed thatpatients with non-ulcer dyspepsia and H pylori infection neededtreatment. Although there is doubt about the necessity of treatingH pylori infection in these patients, Sobala and colleagues proposalis probably the preferred screening strategy.

Sobala et al use two ELISAs. Discrepancies in the test resultswere seen in 14-6% of results. We too have found a largediscrepancy (41-9%) with seven ELISAs (unpublished). This lackof agreement could be because commercial antigens are isolatedfrom locally available strains of H pylori. Since several serotypes ofH pylori are observed, a patient infected with a serotype common inone country would probably elicit antibodies that do not react, orslightly react, with antigens from a serotype common in anothercountry. The commercial assay in Sobala et al’s report uses antigensfrom strains common in the UK, whereas we used assays frommanufacturers from different countries, and discrepancies arebound to arise.

Departments of Internal Medicine,Pathology, and Microbiology,

University Hospital Maastricht,6202 BX Maastricht, Netherlands

R. J. L. F. LOFFELDJ. W. ARENDSE. STOBBERINGH

1. Loffeld RJLF, Stobberingh E, Flendrig JA, van Spreeuwel JP, Arends JW.Diagnostic value of an immunoassay to detect anti Campylobacter pylori antibodiesin non-ulcer dyspepsia. Lancet 1989; i: 1182-85.

CORRECTION

Influence of candoxatril on plasma brain natriuretic peptide in heartfailure.-In this letter by Dr Lang and colleagues (July 27, p 255) thepenultimate sentence of paragraph two should have read "Crossreactivity ofthe hBNP antibody with human ANP with this assay was 0%. The

intrasubject coefficient of variability was 7% for samples from patients withchronic heart failure".