Transmission of Helicobacter pylori Infection

Studies in Families of Healthy Individuals

H. M. MALATY, D. Y. GRAHAM, P. D. KLEIN, D. G. EVANS, E . ADAM
& D. J. EVANS
Depts. of Medicine and Pediatrics, Division of Molecular Virology, USDA/ARS
Children's Nutrition Research Center, Baylor College of Medicine, and Veterans
Affairs Medical Center, Houston, Texas, USA
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Malaty HM, Graham DY, Klein PD, Evans DG, Adam E , Evans DJ. Transmission
of Helicobacter pylori infection. Studies in families of healthy individuals. Scand J
Gastroenterol 1991, 26, 927-932
Helicobacter pylori is accepted as the commonest cause of type-B gastritis. Detailed
information about the mode of transmission remains scanty. We investigated the
frequency of H. pylori infection within families, defined as consisting of a husband
and wife with at least one biologic child, all living in the same household. Inclusion
criteria required that both the parents and the children had been born in the United
States, had used no antibiotic or bismuth for the previous 2 months, had no recent
major illness or surgical operation, and had no symptoms referable to the upper
gastrointestinal tract. H. pylori infection was identified with a "C-urea breath test
and an enzyme-linked immunosorbent assay for anti-H. pylori IgG. Forty-one families
For personal use only.

(151 healthy individuals) were enrolled. Before the results of the H. pylori tests were
known, one parent was selected as the index subject. H. pylori infection clustered;
that is, 68% of spouses of H. pylori-infected index subjects were also H. pylori-
infected, compared with 9% of spouses of H. pylori-qegative index subjects
( p < 0.0001). The children of infected index parents were also more likely to be
infected than children of uninfected index p a r e n t s 4 0 % versus 3%, respectively
(p < 0.0001)-and the results in the children were independent of whether the father
or the mother was the index subject. Clustering of H. pylori infection within families
suggests person-to-person transmission or common source exposure. The high fre-
quency of H. pyforiinfection in spouses suggests that genetic factors are less important
than living conditions for transmission of H. pylori infection.
Key words: Campylobacter pylori; clustering; epidemiology; Helicobacter pylori;
transmission
David Y.Graham, M.D., Veterans Affairs Medical Center (IUD), 2002 Holcombe
Blud., Houston, TX 77030, USA

Within the past decade it has been established
that Helicobacter pylori organism is the most
common cause of chronic gastritis and H . pylori
gastritis is strongly linked to peptic ulcer disease
(1). The epidemiology of H . pylori infection is
beginning to be understood, but the data con-
cerning possible reservoirs and transmission are
scanty (2-7). Several studies have investigated
the parents and siblings of children with symp-
tomatic H . pylori infection and have reported a
higher frequency of H . pylori infection among
families of infected symptomatic children than
among controls (8,9). The focus of our studies
has been to attempt to avoid the bias associated
with patient-based studies and perform traditional
epidemiologic studies in the healthy population.
In this study, we investigated whether there was
clustering of H . pylori infection within family
units of healthy volunteers. We defined the status
of the family on the basis of the results of H .
pylori status in an index parent. We found that
H . pylori infection was strikingly more frequent
 928 H. M. Malaty et al.

in the spouse and children of families in whom
the index parent was infected, suggesting that
person-to-person transmission or common-source
infection occurs frequently.
SUBJECTS AND METHODS
Subjects
Families were recruited from the Houston
metropolitan area through advertisement in local
newspapers and by flyers placed at the various
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CAP) of H. pylori (10,ll). Serum samples were
scored as positive for the presence of IgG anti-
H. pylori antibody if the optical density (OD)
was 20.20. This cut-off value was determined by
an analysis of 600patients; 95.3% of the O D
values were >0.25 or c0.15 (11).
A 13C-urea breath test was performed to
determine whether the H . pylori infection was
active (12,13). The test was scored as positive
when the urease activity was 30.50 pmol/min. In
the case of children under 2 years of age, because

facilities in the Texas Medical Center. A family
unit was defined as a husband and wife with at
least one biologic child who all lived in the same
household. Enrollment criteria required that all
family members had been born in the United
States and that they considered themselves to be
in good health. Each family member completed
a standard questionnaire, which was reviewed
with a trained interviewer. The questionnaire
asked information on: a) demographic factors
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of their small surface area, the cut-off criterion
of 13C enrichment was >6% over base line for
the duration of the test period. This corresponds
to the level of infection present in adults with
known H. pylori infection.
H. pylori infection was defined as a positive
enzyme-linked immunosorbent assay (ELISA) or
a positive urea breath test. The gender of the
index parent was chosen by odd and even numbers
before the results of any tests were known.

such as age, race, gender, educational level,

occupation, family income, and marital status; Statistical analyses
b) personal health; c) the presence and the Families were identified on the basis of the H.
frequency of symptoms referable to the upper pylori status of the index parent. Two groups
gastrointestinal tract (such as indigestion, heart- were defined: the negative index group, in which
burn, sour stomach, nausea/vomiting, burning the index parent was not infected with H. pylori,
pain in the stomach area, and burning pain in the and the positive index group, in which the parent
chest); and d) the use of any medications during was infected. The data were analyzed by t test
the preceding 2 months, specifically antibiotics,
bismuth-containing compounds, or nonsteroidal
antiinflammatory drugs. Each enrollee was also Table I. Summary of study populations
questioned about tobacco and alcohol use and
whether they kept pets at home. Families were Positive Negative
index index
excluded if a member had a history of peptic (n = 19) (n = 22)
ulcer or frequent symptoms (defined as occurring
more than once a month) referable to the upper Family members* 54 56
No. of family members 4 4
gastrointestinal tract. (median)
The study was approved by the Institutional No. of children 35 34
Review Board for the VA Medical Center and Age Of parents,years
Median 36 33
Baylor College of Medicine. Each volunteer gave R~~~~ 19-53 22-40
written, informed consent before participating in Age ofchildren, years
the study. Parents had to certify their children's Median 9t 6t
Range 1-18 2-17
assent by their signature before the children could ~ ~income,~ USDi l 15-25,000
~ 15-25,000
participate in the study. (annual)
A serum sample was obtained from each subject Race: 12:7 6:16
for evaluation of IgG antibody to the high * Excludingthe index case,
molecular weight cell-associated protein (HM- t p = 0.05, Wilcoxon rank test.
 Transmission of H. pylori Infection 929

Table 11. Relation between H . pylori infection in family members and H . pylori status of the index parent

Spouses, Children, Total,

Group no. (%pas.)* no. (%pas.) no. (%pos.)
Positive index parent
Fathers ( n = 10) 10 (80%) 16 (37%) 26 (53%)
Mothers ( n = 9) 9 (55%) 19 (42%) 28 (46%)
Total (n = 19) 19 (68%) 35 (40%) 54 (50%)
Negative index parent
Fathers ( n = 11) 11 (0%) 18 (0%) 29 (0%)
Mothers (n = 11) 11 (18%) 16 (6%) 27 (11%)
Total ( n = 22) 22 (9%) 34 (3%) 56 ( 5 % )
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* Percentage with H . pylori infection.

and the Mantel-Haenszel chi-square using the
SAS program (SAS Institute, Cary, N.C., USA).
The t test or Wilcoxon rank test analyses were
used to test the differences between the positive
index group and the negative index group with
regard to the age of the children and the parents,
the mean number of family, and the family
income of the parents. We also examined the
For personal use only.
in 22 families and was infected (positive index)
in 19 families. The two groups of families were
comparable ( p > 0.1) with regard to the number
of family members, the age of children and adults,
and family income. The children of the unin-
fected index parent were slightly but signifi-
cantly younger than those of the infected index
parents (Table I).

frequencies of H . pylori infection among the two
groups to look for evidence of clustering of H .
pylori infection within the positive index families.
The index case was not counted in the calculations
to determine the percentage infected in the family
group.
RESULTS
Forty-one families (151 healthy individuals)
residing in different geographic regions of the
Houston Metropolitan area were enrolled. The
median number of family members was four
(range, three to six members). The index parent
was not infected with H . pylori (negative index)
The frequency of H . pylori infection was
strikingly higher among families who had a
positive index parent (mother or father) than
those who had a negative index parent-50%
compared with 5%, respectively ( p < 0.001).
Because of the known effect of age on the
prevalence of H . pylori infection, we examined
the prevalence of H. pylori infection among
spouses separately from the children. The pattern
of clustering of the infection within families was
still evident; 13 spouses of the 19 positive index
cases (68%) were infected, compared with 9%
(2 of the 22) of spouses of negative index
cases ( p < 0.001). Infection in the spouse was
independent of whether the index case was the

Table 111. Prevalence of H. pylori infection in black and white families

Positive index Negative index

Black, White, Black, White,

no. (%pas.) no. (%pas.) no. (%pos.) no. (%pos.)

Spouses 12 (83%) 7 (42%) 6 (16%) 16 (6%)

Children 20 (55%) 15 (20%) 10 (0%) 24 (0%)
Total 32 (65%) 22 (27%) 16 (12%) 40 (3%)

Index cases were not included in the calculation.

 930 H . M . Malaty et al.
husband or the wife. Similarly, children in
households with a positive index parent were
more likely to be infected than children of a
negative index parent (40% compared with 3%,
respectively, p < 0.001) (Table 11).
Black families were overrepresented in the
positive index group (12 of 19) compared with
the negative index group (6 of 22) ( p < 0.05).
We therefore analyzed each race separately to
determine whether the clustering phenomenon
was independent of race; the pattern of clustering
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was still evident (Table 111).
The results of the two tests, ELISA and urea
breath test, were concordant in 93%. The ELISA
was positive and the urea breath test negative in
nine (three children and six adults). This is not
unexpected, as the urea breath test is sensitive to
recent use of agents that suppress H. pylori. One
adult was followed up, and her ELISA value was
noted to decrease with time, suggesting that
her infection was being eradicated. The two
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individuals with positive urea breath test and
negative ELISA were both children, and this
probably represents the known delay in acqui-
sition of an antibody response after recent H.
pylori infection. Exclusion of the individuals with
discordant results would not change the results
of the study.
DISCUSSION
The design of this study was unique because it
was based on healthy asymptomatic volunteers
and not on the study of individuals in contact
with patients with symptomatic H . pylori infection
(many with peptic ulcers) (8, 9, 14). Our design
enabled us to examine the transmission of H .
pylori infection within normal households not
at high risk for transmission via contaminated
instruments or through patient contact. The high
frequency of H. pylori infection among the
spouses and the children living in the same
household with a positive index parent strongly
support a process of person-to-person trans-
mission or a common source of infection, or both.
Transmission within families has not yet been
well studied. One small serologic study found
that the frequency of complement-fixing anti-
bodies was not increased among siblings and
children or spouses of infected patients (15). In
another small study the frequency of infection in
children of family contacts (four of eight) was
similar to that among children in orphanages and
higher than among controls (14). Another study
showed that direct family contacts of four H .
pylori-infected children were more likely to have
antibody than age-matched controls (8). One
recent study investigated the families of 27
children with H. pylori gastritis, of whom 13 had
duodenal ulcer disease (9). They were able to
study 34 parents (including 14 couples) and found
a higher prevalence of H. pylori antibody among
parents of H. pylori-infected children than among
parents of uninfected children (9). H . pylori
infection was also more frequent among the 22
siblings (only those over age 6 years were studied)
of infected children than among local controls.
Drumm et al. (9) found that mothers of H. pylori-
infected children were more likely to be infected
than fathers of H . pylori-positive children. This
conclusion was based on the larger proportion
(37.5% infected) of the fathers of H. pylori-
negative children being infected. We were unable
to confirm this observation. In the Drumm et al.
study the rate of infection among mothers of H .
pylori-negative children was not statistically dif-
ferent from that of fathers of H . pylori-negative
children, and the origin of the families, the race,
socioeconomic status, or the possible effects of
single parenting were not taken into account.
The mode(s) of transmission of H. pylori
infection is unknown, but the geographic and
social patterns of H . pylori infection are consistent
with fecal-oral transmission as one important
pathway (2, 3, 7 , 14-16). Fecal-oral transmission
is also consistent with recent data from Lima,
Peru, demonstrating a direct association between
the prevalence of H. pylori infection and source
of drinking water (17). H. pylori has not yet been
isolated from the environment, but the technology
is now available (for example, cDNA probes) to
address this question. Iatrogenic transmission of
H. pyloriinfection has been documented (18, 19),
and the high prevalence of H. pylori infection in
endoscopists who frequently did not use gloves
suggests that the disease is also spread from

instruments contaminated with gastric secretions
(gastric secretion/oral spread) (20). H . pylori has
also been recovered from dental plaque (21),
and, although this appears to be a rare
phenomenon, it emphasizes that there may be
many potential pathways for transmission.
The higher prevalence of H . pylori infection
among black families was consistent with our
previous studies (5,6), which demonstrated that
the age-adjusted prevalence of H . p y l o r i infection
is approximately twice as great in blacks as in
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whites; this difference remained after adjustment
for socioeconomic factors. The racial difference
in apparent susceptibility to H . pylori infection
remains unexplained. The high frequency of H .
pylori infection in spouses suggests that genetic
factors are less important than living conditions
for transmission of H . pylori infection, and this
is confirmed by the finding from this study that
identical twins (age 16 years) in one black family
were discordant for H . pylori infection. Ad-
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ditional studies in twins are in progress.
ACKNOWLEDGEMENTS
This work was supported by the Department of
Veterans Affairs; by grant DK 39919 from the
National Institute of Diabetes and Digestive and
Kidney Diseases; by the U.S. Department of
Agriculture/Agricultural Research Service Chil-
dren's Nutrition Research Center; by the Baylor
College of Medicine General Clinical Research
Center at The Methodist Hospital under grant
RR-00350 from the Division of Research Ser-
vices, National Institutes of Health; and by the
generous support of Hilda Schwartz. The in-
vestigators also acknowledge the help of Gloria
Thompson, Valeria Tapscott, and Sara Sekely.
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Received 1 February 1991

Accepted 4 April 1991
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