Prevalence of Helicobacter pylori infection among sewage workers

Objectives An increased risk for gastric cancer among sewage workers has been described in several studies. During the last decade the bacterium Helicobncter pylori has emerged as one important risk factor for gastric cancer and is now considered a class I carcinogen by the International Agency for Research on Cancer. The route of transmission for this bacterium remains unclear, but fecal-oral transmission has been proposed. If true, this might entail a yet undescribed risk for sewage workers. Method The prevalence of immunoglobulin G (IgG) antibodies against H ~ l o r i was studied with a cross-sectional study design in a group of 289 municipal workers. Samples of serum from 151 sewage workers at 11 sewage plants in Sweden and of serum from 138 referents were analyzed. The referents were group matched for age and socioeconomic status. Results The prevalence of IgG antibodies against Hpylori arnong sewage workers did not differ from that of the referents. The adjusted odds ratio (adjOR) was calculated from a logistic model with age and residence as confounding variables (adjOR 0.90, 95% confidence interval 0.53-1.5). The previously described increase in the prevalence of IgG antibodies against H pylori with increasing age was observed. Geographic differences were also observed in the prevalence of Hpylori in Sweden. exposures in sewage work in Sweden do not cause an increased risk of infection with Hpylori.

There are many examples of pathogens spread by human excreta through sewage water. Polio viruses have been both isolated and detected by polymerase chain reaction (PCR) from sewage water (1). Clark et a1 (2) reviewed early reports about risks for infectious diseases among sewage workers. Sltinh@j reported an increased occurrence of antibodies against hepatitis A virus in Danish sewage-exposed worlters (3). Heng et a1 (4) described an increased risk for hepatitis A infection among sewage workers in Singapore.
In 1982 Helicobacter pylori was first isolated in humans (5), but the route of transinission still remains unclear (6). The bacterium has been isolated from human feces by Thomas et a1 (7) and Kelly et a1 (S), while other groups have reported failures (9). If there is fecal dissemination, an exposure for H pylori is conceivable among sewage workers.
The risk for H pylori infection has been described in other occupational settings. Nurses were at increased risk (lo), but dental workers were not (11,12). In one study of gastroenterologists an increased risk for infection with Hpylori was reported (13), while another study found no increased risk (14). Although not conclusive, these studies indicate that some occupational exposures may cause infection with H pylori.
H pylori has been associated with several types of gastric disease, for example, chronic gastritis (15), atrophic gastritis (16), and peptic ulcers (17, 18). H p ylori is also associated with an increased risk for cancer of the stomach (19), and recently the International Agency for Research on Cancer (IARC) classified H pylori as a humail class I carcinogen (20). Several epidemiologic studies have described increased risks for various cancers among sewage workers, among them cancer of the stomach (21-23). An atlalysis of the Cancer-Environment Register of Sweden for the incidence of stomach cancer by industry and occupation showed a significantly increased risk for stomach cancer in workers em-ployed among waterworks (24). These workers are often engaged at both ~nunicipal drinking water plants and sewage plants.
The evidence of an increased incidence of gastric cancers among sewage workers formed the impetus for this study of possible exposure for H pylori among sewage workers. The hypothesis tested is whether sewage workers are at risk to be infected by H p y l o r i in their work.

Subjects and methods
The prevalence of immunization against H pylori was determined in a group of Swedish sewage workers. The study design was cross-sectional. All 156 workers employed at the municipal plants treating waste water or sludge in 11 municipalities in mid-Sweden were invited to participate, and 151 (97%) did so. The referents were selected from laborers from the same, or closely situated, local authorities. The result was a group matched for geographic location. They were also group matched for the two well-established confounding factors regarding H pylori infection, age (f 5 years) and socioeconomic status (25). Gender has not been reported to be important in this context. One hudred and forty-seven referents meeting these criteria were found, and 138 (94%) participated. The mean age was 46.5 (SD 9.95) years for the participating sewage workers and 45.4 (SD 10.4) years for the participating referents. Nine of the participating sewage workers and one of the referents were women.
Data about current and previous jobs reflecting exposure to sewage were collected through a questionnaire to each participant in the study.
A blood sample for the serum analysis was collected from each worker by routine venipuncture. After centrifugation the serum samples were kept at -1 8OC and analyzed in batches. Sera were examined for immunoglobulin G (IgG) antibodies using the HM CAPTM immunoassay (Enteric Products Inc, New York, United States), according to the instructions of the manufacturer. The sensitivity and specificity of this assay ranged from 94% to 98% (26) and from 92% to 97% (27), respectively. In a few cases with borderline results the sera were reanalyzed using a commercial immunoblot technique (Genelabs Diagnostics, Singapore).
The project was discussed with, and supported by, the employer and the local union at each place. In carying through the project we also had assistance from several local occupational health care units.
Statistical analyses with 2 x 2 table statistics and logistic regression were performed using the computer programs Epi Info (Centers for Disease Control, Atlanta, Georgia, United States and World Health Organization, Geneva, Switzerland), and SPIDA (The Statistical Laboratory, Macquarie University, Australia). Relative risks with 95% confidence intervals (95% CI) were calculated in the 2 x 2 table analyses. Odds ratios (OR) and adjusted odds ratios (adjOR) with 95% confidence intervals were calculated from the logistic regression models. The near collinearity diagnostics for the logistic regression analysis in SPIDA, using condition numbers and variance decomposition proportions, was applied.
In the crude 2 x 2 table analysis there was no increase in the relative risk for seropositivity for Hpylori among the sewage workers when they were compared with the referents (table 1). Neither was there any difference between the sewage worliers and the referents in an agestratified analysis (table 2). However, the previously re-  ported increasing prevalence with age was seen in this analysis. Logistic regression analyses were performed to control for possible confoundi~lg. The dichotomous dependent variable in the logistic regression analyses was iinmunization against Hpylori. The exposure was described in the modeling by a dichotomous variable for present employment at a sewage plant ("sewage worker"). Three alternative exposure variables were also tried, but the results did not change. These alternative variables were the two dichotomous variables "ever had occupational sewage exposure" and "any exposure to sewage in the current job" and the continuous variable "years in sewage worlt." The known confounder age was included as a confounder variable. Due to small numbers in some municipalities four geographic strata were used to control for possible confounding by geography: Gavle, Tierp, and Enltoping in the southeast (region 1); the largest city in the study, Uppsala (region 2); Sates and Smedjebacken in southern Dalarna (region 3); and Alvdalen, Orsa, Mora, and Rattvilt in northern Dalarna (region 4).
In crude analyses, with logistic regression models with a single independent variable, neither of the four alternative exposure variables showed an increased risli for the sewage worlters (table 3). However, there were statistically significant increased odd ratios (OR) for the confounders age and geographic region. Although not completely consistent, one difference between the geographic regions was the proportion of rural population in the different municipalities. Thus this socioeconomic variable was also included in the analyses.
A logistic model with the exposure variable "sewage worker" and the confounders age and geographic regions indicated no increase in the risk for immunization against H yylori among the sewage workers. The adjOR was Table 3. Odds ratios (OR) and 95O/ 0 confidence intervals (95% GI) calculated from crude logistic regression analyses (univariable models) for the presence of immunoglobulin G (IgG) antibodies to Helicobacterpyloriamong sewage workers and their referents. 0.90 (95% CI 0.53-1.5). This analysis also showed an age dependence and regional differences with the same pattern and magnitudes in risk estimates as the crude analyses. Using the proportion of the rural population in the model instead of the geographic regions resulted in rislt estimates close to those determined with the crude analyses.
This study showed no increased risk for infection with H l~ylol-i among sewage worlters. Consequently it does not support the hypothesis that H pylovi infection is a cause of the increased risk of gastric cancer among sewage workers.
The Eurogast study group (28) reported a sixfold increase in the risk for gastric cancer in a H pyloriinfected population, when compared with an uninfected population. In a background population with 30% seropositivity for H pylori, almost all the sewage-exposed persons should have been seropositive, if Hpylori infection alone was to explain the doubled risk for gastric cancer. The relative rislt for gastric cancer among the sewage-exposed workers has been reported to be approximately 2 to 2.5 (21, 22).
The number of nonparticipants among the exposed and referents was small and, therefore, was not expected to affect the validity of the study. In view of the studied effect variable, not giving any symptoms in most cases, a differential selection of individuals is not likely. Misclassification of exposure could conceal a possible overrisk. All the participating individuals completed the questionilaire about job tasks. Some presently unexposed persons were found to have had previous exposure to waste water or sewage sludge. Due to the chronic, if not next to lifelong, nature of the H ~~jdori infection, these persons were treated as exposed in one separate analysis. There were also some workers not employed at sewage plants, for example, construction worlters repairing pipes, who were occasionally exposed to sewage water in their jobs. These men were also considered exposed in another separate analysis. The alternative analyses did not change the conclusions about waste water or sewage sludge as a risk factor for H p),lori infection.
It is not likely that there was any reduction in the studied prevalence due to healthy worlter selection. The referents were also active workers with a comparable degree of manual worlt. Furthermore, the dependent variable in our study, prevalence of IgG antibodies against H pylori, is related to morbidity for very few of the affected.
The referents were group-matched for age, socioeconomic status, and geography to reduce the risks bias.
These possible confounders should have minimal effect on the study results. Therefore, our finding of an increased risk for infection with H pylori in the northwestern region does not affect our conclusion about no observed risk in relation to sewage exposure. This previously not described geographic difference in Sweden cannot be explained by our study.
One might suspect that the frequent use of antibiotics could eradicate H pylori and thus account for reduced prevalence of antibodies against this bacterium. However, the presence of specific antibodies does not protect against the recurrence of infection after temporary clearance (29). Furthermore, monotherapy of the H pylori infection with a single antibiotic does not effectively eradicate the organism (30). Recently one Canadian study also showed that antibiotics taken in the preceding year had no effect on Hpylori prevalence (31).
The previously observed increased risk for gastric cancer among sewage-exposed workers in Sweden is not based on today's exposures. The induction-latency period for cancers is normally decades, and the possible causes of this observed overrisk should be searched for at least 20 to 30 years earlier in time. The virulence of H pylori may be too low to facilitate an infection at present exposure levels. If the observed increase in prevalence with increasing age in the population is a cohort effect, one would also expect that the potential exposure for H pylori through waste water may have been higher among the sewage workers some decades ago. However, the age-stratified analysis done in this study does not indicate an increased risk for H pylori infection among the oldest sewage workers when compared with their agematched referents.
In a recent study on H pylori infection and foreign travel, it was found that none of 133 young adult Swedish seronegative travelers seroconverted after episodes of gastroenteritis in developing countries (32). Since gastroenteritis is a marker of exposure to fecally contaminated food or water, this possible Hpylori challenge did not change the infection rate. H pylori is probably acquired at a young age especially in developing countries (33, 34). It may be that adults are protected against the infection due to a more competent immune defense system.
The present exposures in sewage work in Sweden do not cause an increased risk for infection with H pylori. Consequently, it is not probable that the previously observed increased risk for gastric cancer among Swedish sewage workers is explained by Hpylori infection. Other factors influencing the risk for gastric cancer, such as dietary factors, smoking habits, and other occupational exposures, must be considered in future studies of this tumor among sewage workers (35, 36). Although this study indicates that a possible presence of these bacteria in waste water is of no significance for the health of sewage workers, sewage-contaminated drinking water may still constitute a public health risk. Therefore, further studies of the possible spreading of Hpylori through waste water may be warranted, especially in areas with a high prevalence of the infection.