No abstract

Fifty-four of 59 (91.5%) clarithromycin-resistant isolates of Helicobacter pylori from different patients possessed either the A2143G (formerly A2058G) or the A2144G (formerly A2059G) mutation in the gene encoding 23S rRNA. The A2143G mutation was significantly more likely to occur in isolates with MICs exceeding 64 mg/L (65% versus 30% with the A2144G mutation; P = 0.01). The majority (26 of 31; 83.9%) of isolates with the A2143G mutation had MICs exceeding 64 mg/L. Peptic ulcer disease recurred in a substantial proportion of patients infected with H. pylori strains containing either the A2143G or the A2144G mutation.

We present a molecular epidemiologic study, based on an analysis of vacA, cagA and cag right end junction genotypes from 1042 Helicobacter pylori isolates, suggesting that H. pylori was present in the New World before Columbus. Eight Native Colombian and Alaskan strains possessed novel vacA and/or cagA gene structures and were more closely related to East Asian than to non-Asian H. pylori. Some Native Alaskan strains appear to have originated in Central Asia and to have arrived after strains found in South America suggesting that H. pylori crossed the Bering Strait from Asia to the New World at different times. ß 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

Metronidazole (Mtz) is a critical ingredient of modern multidrug therapies for Helicobacter pylori infection.Mtz resistance reduces the effectiveness of these combinations. Although null mutations in a rdxA gene that encodes oxygen-insensitive NAD(P)H nitroreductase was reported in Mtz-resistant H. pylori, an intact rdxA gene has also been reported in Mtz-resistant H. pylori, suggesting that additional Mtz resistance mechanisms exist in H. pylori. We explored the nature of Mtz resistance among 544 clinical H. pylori isolates to clarify the role of rdxA inactivation in Mtz resistance and to identify another gene(s) responsible for Mtz resistance in H. pylori. Mtz resistance was present in 33% (181 of 544) of the clinical isolates. There was marked heterogeneity of resistance, with Mtz MICs ranging from 8 to >256 g/ml. rdxA inactivation resulted in Mtz MICs of up to 32 g/ml for 6 Mtz-sensitive H. pylori strains and 128 g/ml for one Mtz-sensitive strain. Single or dual (with rdxA) inactivation of genes that encode ferredoxin-like protein (designated fdxB) and NAD(P)H flavin oxidoreductase (frxA) also increased the MICs of Mtz for sensitive and resistant strains with low to moderate levels of Mtz resistance. fdxB inactivation resulted in a lower level of resistance than that from rdxA inactivation, whereas frxA inactivation resulted in MICs similar to those seen with rdxA inactivation. Further evidence for involvement of the frxA gene in Mtz resistance included the finding of a naturally inactivated frxA but an intact rdxA in an Mtz-resistant strain, complementation of Mtz sensitivity from an Mtz-sensitive strain to an Mtz-resistant strain or vice versa by use of naturally inactivated or functional frxA genes, respectively, and transformation of an Mtz-resistant Escherichia coli strain to an Mtz sensitive strain by a naturally functional frxA gene but not an inactivated frxA gene. These results are consistent with the hypothesis that null mutations in fdxB, frxA, or rdxA may be involved in Mtz resistance.

The epidemiology of Helicobacter pylori infection and risk factors associated with its transmission are not well understood. Kazakhstan is country with two ethnic groups, Asian (Kazakhs) and Western (Russians), living under similar socioeconomic conditions. The aim of this study was to examine the seroepidemiologic pattern of H. pylori and hepatitis A among the same individuals from both ethnic groups, with emphasis on water source and household sanitation practices. This was a cross-sectional seroepidemiologic study conducted among unrelated healthy individuals in Kazakhstan. From May through August 1999, individuals between the ages of 10 and 60 years from Almaty, Kazakhstan, were invited to participate. Demographic information, socioeconomic factors, living conditions, and various aspects of the local household environment including access to water were collected. A clean water index (CWI) was created based on combined factors, consistency of boiling water before drinking, frequency of storing and reusing water, and frequency of bathing and showering. H. pylori and hepatitis A antibodies were assessed by enzyme-linked immunosorbent assay. Two hundred eighty-eight individuals between the ages of 10 and 60 years participated. The prevalence of H. pylori infection was almost identical among the two ethnic groups (Russians 79% and Kazakhs 80%). H. pylori infection was inversely correlated with the CWI (i.e., 56%, 79%, and 95% for high, middle, and low, respectively (P < .05). Drinking river water had highest risk of H. pylori infection (OR ‫ס‬ 13.6, 95% CI ‫ס‬ 1.8-102.4; P < .01, compared with tap water). Crowding showed no significant effect on H. pylori prevalence. Anti-HAV antibodies were found in 86% of the population, 90% among the Russians versus 82% among the Kazakhs (OR ‫ס‬ 1.8, 95% CI ‫ס‬ 1.1-3.8, P ‫ס‬ .05). Although the two infections were highly correlated (P < .001), antibody to both infections were present simultaneously in only 74%. The prevalence of H. pylori infection in Kazakhstan is very high. The data suggest that transmission of H. pylori can be water borne, related to poor sanitary practices, or both. The high prevalence of antibodies to H. pylori and HAV among this population is a marker for poor sanitation and hygienic practices. Reducing the rate of H. pylori transmission will require improvements in overall sanitation including clean water, waste disposal, as well as in household hygienic practices.