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Journal of Clinical Microbiology, July 2000, p. 2800-2801, Vol. 38, No. 7
0095-1137/00/$04.00+0
LETTERS TO THE EDITOR
Detection of Helicobacter pylori Antibodies in
Pediatric Populations
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LETTER |
I read with interest the recent article by Sunnerstam et al.
regarding their evaluation of available serologic tests for
immunoglobulin G (IgG) antibodies to Helicobacter pylori in
children (9). I agree that serologic methods used to
determine H. pylori antibody status in children must be
validated. It is well known that the performance of commercial assays
designed to detect IgG antibodies to H. pylori can vary due
to the bacterial antigen preparation they employ, the reference method
used to confirm H. pylori status, and the population studied
(3, 4). Despite the availability of enzyme immunoassays
(EIAs) for serologic diagnosis of H. pylori infection, no
age range is indicated for these assays, implying that these tests can
be used and that their results can be interpreted equally for pediatric
and adult populations.
I disagree with the authors' conclusion that "a positive serological
test for H. pylori infection, particularly for children, needs to be confirmed by a reference method because of the possibility of spontaneous eradication of infection... ."
Increased rates of acquisition of infection, as well as spontaneous
clearance of infection, have been observed primarily in children under
the age of 5 years (5, 6, 7, 8, 10). There was no evaluation
of incidence of infection or accuracy of serology by age group
presented in the paper. The urea breath test (UBT) was not performed
until months after initial collection of sera for serology; therefore,
transient infections were potentially missed. As a minimum safeguard,
reference method testing of a group in whom spontaneous clearance is
suspected to occur should have been performed at the time of serology.
The population available to Sunnerstam et al. for evaluation of the
four serologic tests had an extremely low seroprevalence of H. pylori infection (3%), resulting in only five samples on which to
base an estimation of assay sensitivity. In addition, the confidence
intervals overlap for both the sensitivities and specificities
established for all four of the serologic assays evaluated, indicating
that a statistically significant difference between the four EIAs was
not demonstrated.
Three of the four EIAs demonstrated specificities of >98% based on
the data presented in the article, in contrast to the authors' conclusion that the commercial assays gave a high rate of
false-positive results. The UBT used as the reference method in the
study was 100% sensitive but only 80% specific. This does not support
the authors' final recommendation that positive serology results
obtained with commercial assays should be confirmed using the UBT in
order to detect false positives.
The potential value of serology in the diagnosis of H. pylori infection in children has been shown (1, 2).
Endoscopic examination is an invasive procedure which can be difficult
to perform in children. Although the UBT is noninvasive, serology is
less expensive and more readily available. However, there is no
guarantee that a method that has been demonstrated to be accurate for
adults will perform similarly for children. I acknowledge the authors'
efforts to validate commercial serologic EIAs for H. pylori
infection in children in order to establish their diagnostic utility
for this group.
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REFERENCES |
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|
Chong, S. K. F.,
Q. Y. Lou,
M. A. Asnicar,
S. E. Zimmerman,
J. M. Croffie,
C. H. Lee, and J. F. Fitzgerald.
1995.
Helicobacter pylori infection in recurrent abdominal pain in childhood: comparison of diagnostic tests and therapy.
Pediatrics
96:211-215[Abstract/Free Full Text].
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Czinn, S. J.,
H. S. Carr, and W. Speck.
1991.
Diagnosis of gastritis caused by Helicobacter pylori in children by means of an ELISA.
Rev. Infect. Dis.
13(Suppl. 8):S700-S703.
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Dunn, B. E.,
H. Cohen, and M. J. Blaser.
1997.
Helicobacter pylori.
Clin. Microbiol. Rev.
10:720-741[Abstract].
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Glupczynski, Y.
1993.
Methodological aspects of serology for the diagnosis of Helicobacter pylori infection.
Eur. J. Gastroenterol. Hepatol.
2(Suppl.):50-53.
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Granström, M.,
Y. Tindberg, and M. Blennow.
1997.
Seroepidemiology of Helicobacter pylori infection in a cohort of children monitored from 6 months to 11 years of age.
J. Clin. Microbiol.
35:468-470[Abstract].
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| 6.
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Kert, R.,
M. Becker,
H. Brösicke,
N. Krüger, and H. Helge.
1997.
Prevalence of Helicobacter pylori infection in Nicaraguan children with persistent diarrhea diagnosed by the 13C-urea breath test.
J. Pediatr. Gastroenterol. Nutr.
25:84-88[CrossRef][Medline].
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Klein, P. D.,
R. H. Gilman,
R. Leon-Barua,
F. Diaz,
E. O. Smith, and D. Y. Graham.
1994.
The epidemiology of Helicobacter pylori in Peruvian children between 6 and 30 months of age.
Am. J. Gastroenterol.
89:2196-2200[Medline].
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| 8.
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Rowland, M.,
D. Kumar,
L. Daly,
P. O'Connor,
P. Vaughan, and B. Drumm.
1999.
Low rates of Helicobacter pylori reinfection in children.
Gastroenterology
117:336-341[CrossRef][Medline].
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| 9.
| Sunnerstam, B., T. Kjerstadius, L. Jansson, J. Giesecke, M. Bergström, and J. Ejderhamn. 1999. Detection of
Helicobacter pylori antibodies in a pediatric population:
comparison of three commercially available serological tests and one
in-house enzyme immunoassay. 37:3328-3331.
|
| 10.
|
Xia, H. H. X., and N. J. Talley.
1997.
Natural acquisition and spontaneous elimination of Helicobacter pylori infection: clinical implications.
Am. J. Gastroenterol.
92:1780-1787[Medline].
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| | | | |
Patrice A. Marchildon
Enteric Products, Inc.
25 E. Loop Rd.
Stony Brook, New York 11790
Phone: (631) 444-8872
Fax: (631) 444-8855
|
| |
AUTHOR'S REPLY |
Marchildon points out that the absence of age ranges for commercial
enzyme immunoassays (EIAs) for serological diagnosis of Helicobacter pylori infection implies that test results can
be interpreted equally for pediatric and adult populations. This is
probably not the case, even for commercial assays. Crabtree et al.
(1), using their in-house assay, found that 50% of children with H. pylori gastritis would have been considered
seronegative if the adult cutoff value had been used.
Marchildon does not agree with our conclusion that a positive H. pylori EIA result has to be verified by a reference method, especially for children, because of the possibility of spontaneous eradication of infection. As we pointed out in our article, recent data
(2) suggest, though, that infection with H. pylori and later spontaneous clearance of the infection might well
occur in more than 10% of Swedish children less than 2 years of age. It has also been shown (3) that seroreversion occurs up to 6 months later than eradication of infection.
In our comparison of the performances of the four seroassays, 21 of 169 samples came from children less than 2 years old and 62 of 169 samples
came from children less than 5 years old. The chance of spontaneous
eradication of infection, without concomitant seroreversion, was
accordingly high with our material. Evaluations of incidence of
infection by age group was beyond the scope of our study, since it was
a purely methodological and not an epidemiological study. The study
population was too small to allow analyses of accuracy of serology by
age group.
Even though samples for reference methods were not obtained until
months after the initial collection of sera for serology in our study,
there was no possibility of transient infections being missed,
resulting in an apparently false-positive serology, as suggested by
Marchildon. The only transient infections that could possibly have been
missed in our study would have been infections that both occurred and
disappeared between the first and the second serum samples (drawn from
each individual at the same time that the reference sample was taken),
and those infections would not have affected the rate of false
positives revealed by the reference method.
Formal sensitivity and specificity rates were not calculated for the
subset of 169 serum samples used in the comparison of the four
seroassays, since reference methods were not analyzed for more than the
17 samples with discordant results and the 4 samples with concordant
positive results. A valid reference method, used for all samples, is
the prerequisite for calculations of sensitivity and specificity.
Therefore, the terms "false positives" and "false negatives"
were used in this part of the work, to avoid giving the appearance that
formal sensitivities and specificities could be calculated.
For financial reasons, it was not possible to use 13C-UBT
in all 169 cases. Therefore, we chose to examine the samples yielding concordant seropositive results and those with discordant results in
the seroassays. H. pylori is an uncommon infection among
Swedish children (2, 4), and the risk that all four tested
seroassays might yield false-negative results for the same patient for
such an uncommon infection is probably very low.
The low specificity of the 13C-UBT with our small
unpublished pediatric series of samples used for validation of use of
the UBT for children simply reflects 1 of 39 patients with a raised 13C-UBT result having a normal biopsy. For another small
unpublished pediatric group (40 patients, aged 5 to 16 years), Oksanen
et al. using the same 13C-UBT found a sensitivity and
specificity of 100%. For a larger group of adults (5)
investigated by Oksanen et al. with the same UBT, the sensitivity and
specificity were 92 and 95%, respectively. With a larger pediatric
series, the values of sensitivity and specificity will be more reliable.
| |
REFERENCES |
| 1.
|
Crabtree, J. E.,
M. J. Mahony,
J. D. Taylor,
R. V. Heatley,
J. M. Littlewood, and D. S. Tompkins.
1991.
Immune responses to Helicobacter pylori in children with recurrent abdominal pain.
J. Clin. Pathol.
44:768-771[Abstract/Free Full Text].
|
| 2.
|
Granstrom, M.,
Y. Tindberg, and M. Blennow.
1997.
Seroepidemiology of Helicobacter pylori infection in a cohort of children monitored from 6 months to 11 years of age.
J. Clin. Microbiol.
35:468-470.
|
| 3.
|
Lerang, F.,
J. B. Haug,
B. Moum,
P. Mowinckel,
T. Berge,
E. Ragnhildstveit, and A. Björneklett.
1998.
Accuracy of IgG serology and other tests in confirming Helicobacter pylori eradication.
Scand. J. Gastroenterol.
33:710-705[CrossRef][Medline].
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| 4.
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Lindkvist, P.,
D. Asrat,
I. Nilsson,
E. Tsega,
G. L. Olsson,
B. Wretlind, and J. Giesecke.
1996.
Age at acquisition of Helicobacter pylori infection: comparison of a high and a low prevalence country.
Scand. J. Infect. Dis.
28:181-184[Medline].
|
| 5.
|
Oksanen, A.,
B. Bergström,
A. Sjöstedt,
A. Gad,
B. Hammarlund, and R. Seensalu.
1997.
Accurate detection of Helicobacter pylori infection with a simplified 13C urea breath test.
Scand. J. Clin. Lab. Investig.
57:689-694[Medline].
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Bengt Sunnerstam
Department of Pediatrics
Central Hospital
Hjortvägen 4
654 68 Karlstad, Sweden
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Journal of Clinical Microbiology, July 2000, p. 2800-2801, Vol. 38, No. 7
0095-1137/00/$04.00+0
