Horizontal versus Familial Transmission of Helicobacter pylori

Abstract

Transmission of Helicobacter pylori is thought to occur mainly during childhood, and predominantly within families. However, due to the difficulty of obtaining H. pylori isolates from large population samples and to the extensive genetic diversity between isolates, the transmission and spread of H. pylori remain poorly understood. We studied the genetic relationships of H. pylori isolated from 52 individuals of two large families living in a rural community in South Africa and from 43 individuals of 11 families living in urban settings in the United Kingdom, the United States, Korea, and Colombia. A 3,406 bp multilocus sequence haplotype was determined for a total of 142 H. pylori isolates. Isolates were assigned to biogeographic populations, and recent transmission was measured as the occurrence of non-unique isolates, i.e., isolates whose sequences were identical to those of other isolates. Members of urban families were almost always infected with isolates from the biogeographic population that is common in their location. Non-unique isolates were frequent in urban families, consistent with familial transmission between parents and children or between siblings. In contrast, the diversity of H. pylori in the South African families was much more extensive, and four distinct biogeographic populations circulated in this area. Non-unique isolates were less frequent in South African families, and there was no significant correlation between kinship and similarity of H. pylori sequences. However, individuals who lived in the same household did have an increased probability of carrying the same non-unique isolates of H. pylori, independent of kinship. We conclude that patterns of spread of H. pylori under conditions of high prevalence, such as the rural South African families, differ from those in developed countries. Horizontal transmission occurs frequently between persons who do not belong to a core family, blurring the pattern of familial transmission that is typical of developed countries. Predominantly familial transmission in urban societies is likely a result of modern living conditions with good sanitation and where physical contact between persons outside the core family is limited and regulated by societal rules. The patterns observed in rural South African families may be representative of large parts of the developing world. More than half of the world population is infected with Helicobacter pylori. It was widely believed that the primary mode of transmission is intra-familial, but the chains of infection are poorly understood. We have applied multilocus sequence analysis to H. pylori from two large multi-generation families in rural South Africa. Observations were compared with H. pylori from small, nuclear families in urban areas of the United States, United Kingdom, Colombia, and Korea, as well as with a large global collection from unrelated individuals. Intra-familial transmission of H. pylori was common in urban families but less common in the rural South African families. Instead, the South African families were infected with widely diverse strains, and multiple infections were common. We argue that the apparent predominance of intra-familial transmission in urban societies is a result of good socioeconomic conditions. In high-prevalence areas, opportunities for horizontal transmission are higher, which can result in greater diversity of H. pylori within a family. The patterns of frequent horizontal spread in rural South African families may be representative of large parts of the developing world. This interpretation is supported by the global sample which yielded ample evidence for horizontal inter-familial transmission in many areas of the world.