DNA-level diversity and relatedness of Helicobacter pylori strains in shantytown families in Peru and transmission in a developing-country setting

Abstract

The efficiency of transmission of a pathogen within families compared with that between unrelated persons can affect both the strategies needed to control or eradicate infection and how the pathogen evolves. In industrialized countries, most cases of transmission of the gastric pathogen Helicobacter pylori seems to be from mother to child. An alternative model, potentially applicable among the very poor in developing countries, where infection is more common and the sanitary infrastructure is often deficient, invokes frequent transmission among unrelated persons, often via environmental sources. In the present study, we compared the genotypes of H. pylori from members of shantytown households in Peru to better understand the transmission of H. pylori in developing-country settings. H. pylori cultures and/or DNAs were obtained with informed consent by the string test (a minimally invasive alternative to endoscopy) from at least one child and one parent from each of 62 families. The random amplified polymorphic DNA fingerprints of 57 of 81 (70%) child-mother strain pairs did not match, nor did the diagnostic gene sequences (>1% DNA sequence difference), independent of the child's age (range, 1 to 39 years). Most strains from siblings or other paired family members were also unrelated. These results suggest that H. pylori infections are often community acquired in the society studied. Transmission between unrelated persons should facilitate the formation of novel recombinant genotypes by interstrain DNA transfer and selection for genotypes that are well suited for individual hosts. It also implies that the effective prevention of H. pylori infection and associated gastroduodenal disease will require anti-H. pylori measures to be applied communitywide.

FIG. 1.

Representative RAPD profiles from pools of H. pylori colonies (lanes P) and from individual single colonies (lanes 1 though 5) from child-mother pairs from individual households. The sequences of the four RAPD primers used (primers 1254, 1281, 1283, and 1290) are given in Materials and Methods. (A) Profiles in which predominant strains from the child and mother are closely matched (as was seen in about 30% of the cases) and also the profile of a rare instance in which the child seemed to carry more than one strain in abundance (compare the pooled and the multiple single colonies). The glr gene fragments from the isolates from child 1 and mother 1 (767 bp) were 100% identical. (B) Profiles showing that predominant strains from the child and the mother are unrelated (as was seen in about 70% of the cases) and also that just one strain is predominant in each person. The glr gene fragments (768 bp) from the isolates child 1 and mother 1 were 3.4% divergent (26 base substitution differences), as is typical of unrelated strains (see Fig. 2).

FIG. 2.

Distribution of percent DNA sequence divergence in glr genes in pairs of H. pylori strains from a child and a parent. The numbers on top of each vertical bar indicate the number of strain pairs from family members that exhibited a particular level of divergence.

FIG. 3.

Distribution of relatedness among child-mother H. pylori strain pairs according to the age of the offspring. Taken across all age groups, 24 of 81 (30%) pairs of strains from the child and the mother were perfectly matched or nearly matched (closely related). Similarly, 2 of 11 (18%), 1 of 4 (25%), and 12 of 37 (32%) pairs of strains from the child and father, the mother and the father, and one sibling and another sibling, respectively, were perfectly matched or nearly matched (closely related). All other pairs of strains were not related in their RAPD patterns and gene sequences.