DNA motifs at several informative loci in more than 500 strains of Helicobacter pylori from five continents were studied by PCR and sequencing to gain insights into the evolution of this gastric pathogen. Five types of deletion, insertion, and substitution motifs were found at the right end of the H. pylori cag pathogenicity island. Of the three most common motifs, type I predominated in Spaniards, native Peruvians, and Guatemalan Ladinos (mixed Amerindian-European ancestry) and also in native Africans and U.S. residents; type II predominated among Japanese and Chinese; and type III predominated in Indians from Calcutta. Sequences in the cagA gene and in vacAm1 type alleles of the vacuolating cytotoxin gene (vacA) of strains from native Peruvians were also more like those from Spaniards than those from Asians. These indications of relatedness of Latin American and Spanish strains, despite the closer genetic relatedness of Amerindian and Asian people themselves, lead us to suggest that H. pylori may have been brought to the New World by European conquerors and colonists about 500 years ago. This thinking, in turn, suggests that H. pylori infection might have become widespread in people quite recently in human evolution.Helicobacter pylori is a microaerophilic bacterium with the extraordinary ability to establish infections in human stomachs that can last for years or decades, despite immune and inflammatory responses and normal turnover of the gastric epithelium and overlying mucin layer in which it resides. It is carried by more than half of all people worldwide and has attracted great attention as a major cause of peptic ulcer disease and an early risk factor for gastric cancer, one of the most frequently lethal of malignancies worldwide (for reviews see references 23, 48, and 60).

Treatment failure is a major cause of concern for the Helicobacter pylori-related gastroduodenal diseases like gastritis, peptic ulcer, and gastric cancer. Curcumin, diferuloylmethane from turmeric, has recently been shown to arrest H. pylori growth. The antibacterial activity of curcumin against 65 clinical isolates of H. pylori in vitro and during protection against H. pylori infection in vivo was examined. The MIC of curcumin ranges from 5 g/ml to 50 g/ml, showing its effectiveness in inhibiting H. pylori growth in vitro irrespective of the genetic makeup of the strains. The nucleotide sequences of the aroE genes, encoding shikimate dehydrogenase, against which curcumin seems to act as a noncompetitive inhibitor, from H. pylori strains presenting differential curcumin MICs showed that curcumin-mediated growth inhibition of Indian H. pylori strains may not be always dependent on the shikimate pathway. The antimicrobial effect of curcumin in H. pylori-infected C57BL/6 mice and its efficacy in reducing the gastric damage due to infection were examined histologically. Curcumin showed immense therapeutic potential against H. pylori infection as it was highly effective in eradication of H. pylori from infected mice as well as in restoration of H. pylori-induced gastric damage. This study provides novel insights into the therapeutic effect of curcumin against H. pylori infection, suggesting its potential as an alternative therapy, and opens the way for further studies on identification of novel antimicrobial targets of curcumin.

BackgroundKilled oral cholera vaccines (OCVs) have been licensed for use in developing countries, but protection conferred by licensed OCVs beyond two years of follow-up has not been demonstrated in randomized, clinical trials.Methods/Principal FindingsWe conducted a cluster-randomized, placebo-controlled trial of a two-dose regimen of a low-cost killed whole cell OCV in residents 1 year of age and older living in 3,933 clusters in Kolkata, India. The primary endpoint was culture-proven Vibrio cholerae O1 diarrhea episodes severe enough to require treatment in a health care facility. Of the 66,900 fully dosed individuals (31,932 vaccinees and 34,968 placebo recipients), 38 vaccinees and 128 placebo-recipients developed cholera during three years of follow-up (protective efficacy 66%; one-sided 95%CI lower bound = 53%, p<0.001). Vaccine protection during the third year of follow-up was 65% (one-sided 95%CI lower bound = 44%, p<0.001). Significant protection was evident in the second year of follow-up in children vaccinated at ages 1–4 years and in the third year in older age groups.Conclusions/SignificanceThe killed whole-cell OCV conferred significant protection that was evident in the second year of follow-up in young children and was sustained for at least three years in older age groups. Continued follow-up will be important to establish the vaccine's duration of protection.Trial RegistrationClinicalTrials.gov NCT00289224.

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Antimicrobial susceptibility of 120 Helicobacter pylori isolates to metronidazole, tetracycline, clarithromycin, and amoxicillin was determined, and 77.5, 15, 10, and 6.6% of the isolates, respectively, were resistant. Only rdxA inactivation and both rdxA and frxA inactivation were responsible for metronidazole resistance in 66% (8 of 12) and 33% (4 of 12) of the isolates, respectively. Eradication ofHelicobacter pylori infection by treatment with two antimicrobial agents (clarithromycin and amoxicillin or metronidazole) and a proton pump inhibitor is recommended by various consensus groups (10,16,20). Antimicrobial resistance in H. pylori is a growing problem as it is the most important factor in determining treatment outcome. The prevalence of antimicrobial resistance varies with geographical regions (3, 25). Metronidazole resistance in H. pylori has been shown to be due to mutation in rdxA; mutation in frxA has also been shown to be associated with metronidazole resistance (11,12,23). In Bangladesh, the prevalences of H. pylori infection among infants, children, and adults are 61, 84, and 92%, respectively (1, 21, 22); however, information on antimicrobial susceptibility to commonly used drugs in H. pylori treatment is lacking. This study was conducted to evaluate (i) the prevalence of primary antibiotic resistance to commonly used antimicrobial agents and (ii) the genetic basis for metronidazole resistance in H. pylori isolates from Bangladesh.Consecutive patients attending the Gastroenterology Department of Dhaka Medical College Hospital for upper gastrointestinal endoscopy were enrolled during 1999 to 2001. Diagnosis of peptic ulcer (PU) and non-ulcer dyspepsia (NUD) or gastritis was based on endoscopic examination of the stomach and duodenum. Biopsy samples were taken from each patient for culture.Bacteria were grown in brain heart infusion agar with 7% sheep blood and incubated at 37°C in 5% O 2 , 10% CO 2 , and 85% N 2 for 3 to 6 days. The MICs of amoxicillin, clarithromycin, metronidazole, and tetracycline for the isolates were determined by the agar dilution method as described elsewhere (18,19). All tests were repeated twice, and H. pylori 26695 was used as a control. ␤-Lactamase production was tested by the chromogenic cephalosporin method (6). The molecular mechanism of susceptibility and resistance to metronidazole was studied in 12 isolates. Metronidazole-susceptible (Mtz s ) isolates were further studied (by inactivation of rdxA alone or rdxA and frxA for conversion into an Mtz r phenotype) by transformation of Mtz s isolates with plasmids pBS-rdxA-cam (rdxA::cat) and pBS-frxA-kan (frxA::kan) as described earlier (11,12).A total of 278 consecutive patients between 15 and 78 years of age were enrolled, and among them, 72.7% (202 patients) were male and 27.3% (76 patients) were female. Among the patients, 162 had PU and 116 had NUD and 62.6% (174 of 278) were culture positive for H. pylori. Among the culturepositive patients, 121 (69.5%) were male and 53 (30.4%) were female and 112 (64.3%) had PU ...