Aspects of Helicobacter pylori transmission

The bacterium Helicobacter pylori infects the gastric mucosa of about half of the world's population. The infection causes gastritis and contributes to the development of peptic ulcer disease and gastric cancer. H. pylori infection is associated with low socioeconomic status, is typically acquired in early childhood and once established can persist throughout life unless treated. Person-to-person transmission appears to predominate and the family stands out as the primary framework for transmission.

In this thesis, an initial cross-sectional study aimed to disentangle the independent contributions of H. pylori infections in family members to the risk for the infection in 11 to 13-year old index children from Stockholm schools. H. pylori infections in mothers and in siblings, but not in fathers, were notable risk factors for infection in the index children. Furthermore, birth of the index child in a country with high H. pylori prevalence was an independent risk factor for infection. In addition to the initial standard analysis, a weighted logistic regression method was applied to accommodate additional non-randomly sampled cases. This exemplified how appropriate analysis of epidemiological data from complex sampling schemes can improve precision and maintain validity, while enabling a more complete investigation of risk factors already identified.

A subset of the infected family members underwent gastroscopy and contributed gastric biopsies from which H. pylori was isolated and typed by molecular methods. The same bacterial strains were frequently detected among siblings and between mothers and offspring. No strain concordance was detected between fathers and offspring, but parents sometimes harbored the same strains. The bacterial isolates were also examined with regard to the presence or absence of the cag pathogenicity island (PAI), a bacterial virulence factor.

In a comparison with serological data, serology was supported as a suitable method to determine cag PAI status of H. pylori infections in clinical and epidemiological studies. Moreover, clonal and non-clonal bacterial isolates from members of a family were analyzed in more detail, which included microarray-based genome comparisons. Non-clonal H. pylori isolates exhibited extensive genetic variability, where certain characteristics could be discerned. However, transmission and host adaptation did not appear to be associated with substantial sequence diversity in the bacterial genome.

The present data support a predominantly mother-child and sib-sib transmission of H. pylori, consistent with an important role of intimate contact in the transmission. Furthermore, methodological and microbiological aspects that could aid future research are described. In summary, the findings of this thesis and the discussions thereof shed some light on the characteristics and mechanisms of transmission and persistence of H. pylori infection.

List of scientific papers

I. Kivi M, Johansson AL, Reilly M, Tindberg Y (2005). Helicobacter pylori status in family members as risk factors for infection in children. Epidemiol Infect. 133(4): 645-52.
https://doi.org/10.1017/S0950268805003900

II. Kivi M, Johansson ALV, Salim A, Tindberg Y, Reilly M (2005). Accommodation of additional non-randomly sampled cases in a study of Helicobacter pylori infection in families. Statistics in Medicine. [Accepted]
https://doi.org/10.1002/sim.2386

III. Kivi M, Tindberg Y, Sorberg M, Casswall TH, Befrits R, Hellstrom PM, Bengtsson C, Engstrand L, Granstrom M (2003). Concordance of Helicobacter pylori strains within families. J Clin Microbiol. 41(12): 5604-8.
https://doi.org/10.1128/JCM.41.12.5604-5608.2003

IV. Kivi M, Tindberg Y, Bengtsson C, Engstrand L, Granstrom M (2005). Assessment of the cag pathogenicity island status of Helicobacter pylori infections with serology and PCR. Clin Microbiol Infect. 11(1): 66-8.
https://doi.org/10.1111/j.1469.2004.01021.x

V. Kivi M, Hjalmarsson S, Kupershmidt I, Lundin A, Tindberg Y, Granström M, Engstrand L (2005). Helicobacter pylori genome variability in a framework of familial transmission. [Manuscript]