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.

Figure 1. Helicobacter pylori in family 12 from South Africa.

Circles in the pedigree depict female and squares depict male family members. Numbers in the symbols refer to the patient/isolate identifyer. Empty symbols: no biopsies were taken, because individuals refused to participate or were deceased. Colours of filled symbols indicate the assignment of the isolate to H. pylori populations by Structure 2.0 analysis. Color-coding is shown on the right. Numbers below the symbols indicate the sequence type (ST) of the antrum (upper number) and corpus (lower number) isolates. STs that occurred in more than one individual are highlighted by the same colour. Black horizontal lines between upper and lower ST numbers indicate that antrum and corpus isolates were assigned to different STs. NEG: H. pylori could not be cultivated from the respective biopsy. Individuals where the upper or lower number are missing indicate that only one biopsy was available.

Figure 2. Helicobacter pylori in family 13 from South Africa.

See legend of Figure 1 for details.

Figure 3. Helicobacter pylori in 11 families from the United States, Korea, the United Kingdom, and Colombia.

Meaning of symbols and color-coding as described for Figures 1 and 2. Only one isolate was available per individual. Unique STs are shown in black and identical STs detected within a family are highlighted in red.

Figure 4. Complex sequence mosaics within H. pylori isolates from families.

Long bars represent the merged housekeeping gene fragments (3,406 bp) for the strains from the Coventry family (England, top) and family 13 (South Africa, bottom), and black lines within the bars indicate the position of sequence polymorphisms. Gaps indicate a deletion of six basepairs in the yphC gene in hpAfrica2 strains. Sequences of paired corpus and antrum isolates from members of family 13 are only shown if the sequences were different. Selected identical sequence motifs, i.e., identical single or multiple nucleotide polymorphisms, detected in isolates from at least two family members of family 13, are highlighted in red.