Leprosy is a chronic, dermatological and neurological disease that results from infection with the unculturable pathogen Mycobacterium leprae 1 and causes nerve damage that can lead to severe disabilities. There is no known reservoir for M. leprae other than human beings. New opportunities for understanding the transmission of the leprosy bacillus and its phylogeny have arisen following the determination of the complete 3.3-Mb genome sequence of the TN strain, from Tamil Nadu, India 2 .A notable feature of the M. leprae genome is the exceptionally large number of pseudogenes, which occupy almost half of the TN chromosome 2 . The resulting loss of function most likely accounts for the exceptionally slow growth rate of the bacillus and for researchers' failure to culture it in vitro. Given this extensive genome decay, one might expect to find more genetic variability between different isolates of M. leprae, but initial analysis of SNPs demonstrated that these were very rare, occurring roughly once every 28 kb. RESULTS Complete genome sequence of Br4923The Br4923 strain of M. leprae was chosen for complete genome analysis because it was originally isolated from a patient in Brazil, the country with the second highest leprosy burden, and because Brazil is geographically remote from India Recombination between dispersed repeats?The SNPs associated with dispersed repeats deserve some comment, as they provide evidence for genome plasticity in M. leprae. Variation between different copies of repeat family members had previously been reported 18, 19 , but analysis of two complete genomes provided a richer, more comprehensive dataset. Although all four repeat families (RLEP, REPLEP, LEPRPT and LEPREP) were present in the same copy number and location in both genomes, roughly half of the family members displayed sequence polymorphisms when pair-wise comparisons were performed (Fig. 1). The number of polymorphic sites ranged from one in LEPRPT and REPLEP to six in RLEP. With one exception, these resulted from G-A transitions in the RLEP, LEPRPT and LEPREP elements or single-base indels in LEPREP or REPLEP. The polymorphic sites tend to be occupied by A in the TN strain and by G in Br4923. Variation in REPLEP occurs at position 636, which is occupied either by GGG or GG (Fig. 1). Almost 25% of the total SNPs (38/155) occur in these repeats, which account for a mere 1.16% of the genome. The over-representation of SNPs in these elements may indicate that recombination events between different copies of the repetitive elements result in the dispersal of a particular SNP. This interpretation is supported by the strain-specific bias for A and G in the TN and Br4923 strains, respectively, and the finding that more differences are found toward the center of the element rather than near its ends. In turn, these combined findings render polymorphic sites in repetitive DNA unattractive as potential epidemiological tools. Search for informative SNPsFor phylogenetic and phylogeographic purposes, we determined which SNPs had been inhe...

Aims: To investigate treated water distribution systems in England as a source of Helicobacter pylori. Methods and Results: Water and biofilms were obtained from 11 domestic and seven educational properties and from hydrants, reservoirs and water meters supplied by three water utilities. Samples were cultured on nonselective and antibiotic containing media combined with immunomagnetic separation concentration. Viable helicobacters were not detected in any of the 151 samples but Helicobacter-specific PCR assays detected DNA in 26% of samples from domestic properties, schools and hydrants with the highest frequency in biofilms (42%). Direct sequencing of six selected amplicons confirmed >95% sequence homology to H. pylori. Conclusions: While viable helicobacters were not isolated, evidence was obtained for the presence of Helicobacter DNA, including that of H. pylori. Biofilms on surfaces within water distribution systems may act either as sites for the passive accumulation of helicobacters or as potentially important reservoirs of infection. Significance and Impact of the Study: Our findings strengthen evidence that H. pylori may be transmitted through drinking water. However, there is currently no evidence that viable cells can survive the disinfection levels used in UK mains supplies and the health risk from this source remains unclear.

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Stool antigen-testing allows non-invasive detection of Helicobacter pylori that is indicative of active infection. Three commercial kits are currently marketed in the UK for stool antigen-testing. The aim of this study was to conduct a comparative evaluation of the performances of each of these tests, compared with culture and histological examination of gastric biopsies, for pre-treatment diagnosis of infection in an adult dyspeptic population in south-east England. Examination of 112 stool samples by the Premier Platinum HpSA ELISA (Meridian Diagnostics) and by the Amplified IDEIA HpStAR ELISA (DakoCytomation) kits demonstrated that the latter was more sensitive (81 . 3 versus 93 . 8 %, respectively) and specific (91 . 7 versus 100 . 0 %, respectively). Additionally, the IDEIA HpStAR was easier to interpret, with OD readings of positive and negative results being far from the recommended cut-off, whereas equivocal results that were generated by the HpSA kit were difficult to interpret. Additional testing of 87 of the 112 stools by the ImmunoCard STAT! HpSA kit (Meridian Diagnostics) demonstrated that this test was easier to perform than ELISA and was more sensitive than the HpSA kit but, compared with the IDEIA HpStAR kit, the ImmunoCard test was less sensitive (87 . 8 versus 95 . 9 %, respectively) and specific (89 . 4 versus 100 . 0 %, respectively). Furthermore, the ImmunoCard test generated weakly positive results, correlating with lower OD readings for both ELISA kits, that were difficult to interpret. The Amplified IDEIA HpStAR kit is therefore the most sensitive and specific of the three tests that are available for pre-treatment, non-invasive detection of H. pylori in stool samples in an English adult dyspeptic population.