SUMMARY. Helicobacter pylori (HP) infection can cause hypochlorhydria, a positive risk factor for. Mycobacterium tuberculosis (MTB) infection. This study ...
Epidemiol. Infect. (2003), 130, 87–91. f 2003 Cambridge University Press DOI : 10.1017/S0950268802007653 Printed in the United Kingdom
No association between Helicobacter pylori and Mycobacterium tuberculosis infections among gastrointestinal clinic attendees in Lima, Peru
M. A. T O R R E S 1*, D. J. P A SS A R O 1#, J. W A T A N A B E 2, J. P A R S O N N E T 1, P. SM A L L 1, J. MI Y A G U I 2, C. R O D R I Q UE Z 2, M. A S T E T E 2 A N D R. H. G IL M A N 3 1
Stanford University Medical Center, Stanford, CA, USA Policlı´nico Peruano Japone´s, Lima, Peru 3 Johns Hopkins School of Public Health, Baltimore, MD, USA 2
(Accepted 31 July 2002) SUMMARY Helicobacter pylori (HP) infection can cause hypochlorhydria, a positive risk factor for Mycobacterium tuberculosis (MTB) infection. This study examined the association between HP and MTB infections among persons attending the Policlı´ nico Peruano Japone´s Gastrointestinal Clinic in Lima, Peru. From 23 June 2000 to 18 August 2000, consenting 18–55 year olds who attended the clinic for gastric biopsy gave blood for HP serologic testing, underwent tuberculin skin testing (TST) and completed a social and medical history. Of 128 participating patients, 78 (61 %) were TST positive for MTB, and 107 (84 %) were infected with HP by serology. Of the patients who were HP positive, 67 (63 %) developed positive TST reactions compared to 11 (52 %) of 21 HP-seronegative subjects (OR 1.29 ; 95 % CI 0.54–3.11; P=0.6). There was no association after adjusting for covariates of H. pylori infection (OR 0.78 ; 95% CI 0.23–2.71 ; P=0.7). However, study power was limited by high prevalence of the two infections.
INTRODUCTION Tuberculosis (TB) is one of the world’s most common and highly contagious diseases, causing 2–3 million deaths each year. Mycobacterium tuberculosis (MTB) infects approximately one-third of the world’s population [1], with prevalence as high as 64 % in developing countries [2]. Helicobacter pylori infects approximately one-half of the world’s population, with prevalence as high as 90% among adults in many developing countries [2]. Infection by H. pylori has been associated with a wide range of human illnesses including gastric cancer [3], duodenal ulcer disease and gastric ulcer disease [4]. Both MTB and H. pylori
* Author for correspondence : 100 North Whisman Rd., Apt. 3721, Mountain View, CA 94043, USA. # Current affiliation : University of Illinois School of Public Health, Chicago, IL, USA.
are more common among persons of low socioeconomic status (SES) and those living in densely populated areas, presumably because they are transmitted person-to-person [1, 2, 5–8]. Although H. pylori and MTB infections share many risk factors, no studies have examined the relationship between H. pylori and MTB infection. A prior crosssectional study found an association between prevalence of H. pylori and having had clinical TB, suggesting the two infections may be related [9]. In contrast, a case-control study found no difference in seroprevalence of H. pylori infection between patients with and without clinical TB [10]. However, this small study compared inpatient cases with outpatient controls. Furthermore, because clinical TB represents only a fraction of MTB infections, any true H. pylori–MTB relationship may have been obscured. Several studies have demonstrated that patients are at increased risk for clinical TB after gastrectomy,
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with and without vagotomy [11–13]. The mechanism for this association is unknown. One hypothesis is that the gastric acid barrier prevents ingested MTB from flourishing [14] and causing disease via regurgitation and aspiration from the stomach to the lungs. The normal fasting gastric pH of 1–4 is bactericidal to many enteric pathogens [15–20]. Growth of MTB decreases significantly below a pH of 5 [12]. Gastric disturbances induced by H. pylori infection, in particular inflammation of the gastric corpus [21] with atrophy and hypochlorhydria [22], might similarly increase risk for MTB infection. This cross-sectional study was designed to determine whether there is an association between H. pylori and MTB infection in Peruvians undergoing endoscopy at a private-payer gastroenterology clinic in Lima, Peru. Methods All 18–55 year olds who attended the clinic for elective gastric biopsy, with or without gastric pH measurement, from 23 June 2000 to 18 August 2000 were eligible for enrolment. Subjects were excluded on the basis of prior clinical tuberculosis and BCG vaccination within the last 2 years, as these subjects may have severe local reactions to TST. To minimize the number of false negative TST results, immunocompromised subjects including those with HIV infection, hepatitis B or C and/or cirrhosis, or renal disease were also excluded. Subjects who were pregnant were not permitted to participate. Consenting adults completed a risk factor questionnaire and underwent TST and H. pylori serologic testing. The questionnaire was used to assess 82 demographic and SES risk factors, including age, presence of running water currently and at age 5, smoking history, alcohol use (alcoholism was defined as an affirmative response to at least one of the CAGE questions), household crowding (number of persons/ rooms in house), and antibiotic use within the past year. Subjects were injected with intermediate-strength TST (5 tuberculin units) and asked to return in 48–72 h. A positive skin test was defined as induration o10 mm in diameter. Subjects who did not return within 7 days of TST placement were excluded from analysis [23]. Sera were tested for H. pylori-specific IgG using an enzyme-linked immunosorbent assay (Wampole Laboratories, Cranbury, NJ, USA) run in triplicate. The reported sensitivity and specificity of these kits
relative to biopsy are 98.5 and 98.1%, respectively. Patients were considered positive for H. pylori if 2 of 3 wells contained H. pylori specific IgG antibody. The Wilcoxon two-sample test was used to compare continuous and integer variables. Bivariate prevalence odds ratios were calculated by the x2 test ; odds ratios were used rather than risk ratios to facilitate comparison with adjusted odds ratios obtained by logistic regression. Two-tailed P-values f0.05 were judged significant. Concordance was assessed by the k statistic. RESULTS Of 145 study participants, 130 (90 %) returned within 7 days for TST interpretation ; 128 (88 %) had unequivocal H. pylori serologic results. No subjects were excluded for having active TB or a prior severe reaction to TST. H. pylori and MTB infections were common ; 107 (84 %) of 128 subjects were H. pylori infected by serology and 78 (61 %) of 128 were TSTpositive. Of the 128 subjects analysed, most (106 or 83%) were Peruvian without Asian heritage, 12 (9 %) were Asian, and 5 (4 %) were European or North American ; median age was 35 years. H. pylori-infected subjects were older than uninfected subjects (median age 36 vs. 25 years, P
