Helicobacter pylori from gastric cancer and duodenal ulcer show same phylogeographic origin in the Andean Region in Colombia

Background: A recent report has shown that the phylogenetic origin of Helicobacter pylori based on multi-locus sequence typing (MLST) was significantly associated with the severity of gastritis in Colombia. However, the potential relationship between phylogenetic origin and clinical outcomes was not examined in that study. If the phylogenetic origin rather than virulence factors were truly associated with clinical outcomes, identifying a population at high risk for gastric cancer in Colombia would be relatively straightforward. In this study, we examined the phylogenetic origins of strains from gastric cancer and duodenal ulcer patients living in Bogota, Colombia. Methods: We included 35 gastric cancer patients and 31 duodenal ulcer patients, which are considered the variant outcomes. The genotypes of cagA and vacA were determined by polymerase chain reaction. The genealogy of these Colombian strains was analyzed by MLST. Bacterial population structure was analyzed using STRUCTURE software. Results: H. pylori strains from gastric cancer and duodenal ulcer patients were scattered in the phylogenetic tree; thus, we did not detect any difference in phylogenetic distribution between gastric cancer and duodenal ulcer strains in the hpEurope group in Colombia. Sixty-six strains, with one exception, were classified as hpEurope irrespective of the cagA and vacA genotypes, and type of disease. STRUCTURE analysis revealed that Colombian hpEurope strains have a phylogenetic connection to Spanish strains. Conclusions: Our study showed that a phylogeographic origin determined by MLST was insufficient for distinguishing between gastric cancer and duodenal ulcer risk among hpEurope strains in the Andean region in Colombia. Our analysis also suggests that hpEurope strains in Colombia were primarily introduced by Spanish immigrants. © 2014 Shiota et al

Extremely low Helicobacter pylori prevalence in North Sulawesi, Indonesia and identification of a Maori-tribe type strain: A cross sectional study

Background: Sulawesi in Indonesia has a unique geographical profile with assumed separation from Sundaland. Studies of Helicobacter pylori in this region are rare due to the region's rural location and lack of endoscopy equipment. Indirect methods are, therefore, the most appropriate for measuring H. pylori infection in these areas; with the disposable gastric brush test, we can obtain gastric juice as well as small gastric tissue samples for H. pylori culture. We investigated the prevalence of H. pylori infection and evaluated human migration patterns in the remote areas of North Sulawesi. Methods. We recruited a total of 251 consecutive adult volunteers and 131 elementary school children. H. pylori infection was determined by urine antibody test. A gastric brush test was used to culture H. pylori. We used next-generation and polymerase chain reaction based sequencing to determine virulence factors and multi-locus sequence typing (MLST). Results: The overall H. pylori prevalence was only 14.3 for adults and 3.8 for children, and 13.6 and 16.7 in Minahasanese and Mongondownese participants, respectively. We isolated a single H. pylori strain, termed -Manado-1. Manado-1 was East Asian type cagA (ABD type), vacA s1c-m1b, iceA1 positive/iceA2 negative, jhp0562-positive/β-(1,3) galT-negative, oipA "on", and dupA-negative. Phylogenetic analyses showed the strain to be hspMaori type, a major type observed in native Taiwanese and Maori tribes. Conclusions: Our data support that very low H. pylori infection prevalence in Indonesia. Identification of hspMaori type H. pylori in North Sulawesi may support the hypothesis that North Sulawesi people migrated from north. © 2014 Miftahussurur et al.; licensee BioMed Central Ltd

Helicobacter pylori virulence genes of minor ethnic groups in North Thailand

Background: There are few studies analyzed concurrently the prevalence and genotypes of Helicobacter pylori infection with the ancestor origins from different ethnics, especially with including minority groups. We recruited a total of 289 patients in MaeSot, Thailand (154 Thai, 14 Thai-Chinese, 29 Karen and 92 Hmong ethnics). The virulence genes and genealogy of the strains were determined by PCR-based sequencing. Results: Based on culture and histology/immunohistochemistry, the prevalence of H. pylori infection was 54.5 (158/289). Among 152 isolates cultured, the East-Asian-type cagA was predominant genotype among strains from Hmong, Thai-Chinese and Thai (96.0 48/50, 85.7% 6/7 and 62.7% 47/75, respectively), whilst majority of strains from Karen had Western-type cagA (73.3% 11/15). Patients infected with the East-Asian-type cagA strains had significantly higher activity and intestinal metaplasia in the antrum and activity in the corpus than those with Western-type cagA (P = 0.024, 0.006 and 0.005, respectively). The multilocus sequencing typing analysis discriminated that most strains from Hmong and Thai-Chinese belonged to hspEAsia (92.0 and 85.7%, respectively), whereas strains from Karen predominantly possessed hpAsia2 (86.7%) and strains from Thai were classified into hspEAsia (45.2%) and hpAsia2 (31.1%). Conclusions: Helicobacter pylori genotypes were relatively different among ethnic groups in Thailand and were associated with the source of ancestor even living in a small rural town. Caution and careful check-up are required especially on Hmong ethnic associated with high prevalence of virulence genotypes of H. pylori. © 2017 The Author(s)

Rapid evolution of distinct Helicobacter pylori subpopulations in the Americas

For the last 500 years, the Americas have been a melting pot both for genetically diverse humans and for the pathogenic and commensal organisms associated with them. One such organism is the stomach-dwelling bacterium Helicobacter pylori, which is highly prevalent in Latin America where it is a major current public health challenge because of its strong association with gastric cancer. By analyzing the genome sequence of H. pylori isolated in North, Central and South America, we found evidence for admixture between H. pylori of European and African origin throughout the Americas, without substantial input from pre-Columbian (hspAmerind) bacteria. In the US, strains of African and European origin have remained genetically distinct, while in Colombia and Nicaragua, bottlenecks and rampant genetic exchange amongst isolates have led to the formation of national gene pools. We found three outer membrane proteins with atypical levels of Asian ancestry in American strains, as well as alleles that were nearly fixed specifically in South American isolates, suggesting a role for the ethnic makeup of hosts in the colonization of incoming strains. Our results show that new H. pylori subpopulations can rapidly arise, spread and adapt during times of demographic flux, and suggest that differences in transmission ecology between high and low prevalence areas may substantially affect the composition of bacterial populations

Distribution and clinical associations of integrating conjugative elements and cag pathogenicity islands of Helicobacter pylori in Indonesia

The clinical associations and correlations with other virulence factors such as cag pathogenicity island (PAI) of the Integrating Conjugative Elements Helicobacter pylori TFSS (ICEHptfs), a new type IV secretion system (TFSS) in H. pylori has not been described. Among 103 studied strains from Indonesia, almost all strains (99.0%) contained cag PAI with more than half (55.8%) were intact cag PAI. Patients infected with intact cag PAI strains showed significantly higher antral activity, inflammation and atrophy as well as corporal inflammation than those with non-intact cag PAI strains, confirming the virulence of cag PAI. Over half of strains (53.8%) contained ICEHptfs, predominantly consisted of ICEHptfs3-tfs4a (42.8%) and ICEHptfs3 (16.3%). Although patients infected with ICEHptfs-positive strains had lower H. pylori density, those with the complete ICEHptfs4b strains tended to have higher antral activity than the negative one. In combination, patients infected with combination of intact cag PAI-ICEHptfs-positive strains had more severe inflammation than those with non-intact cag PAI-ICEHptfs-negative, suggesting a possibility of a mutual correlation between these TFSS(s)

Multicenter questionnaire survey for sporadic inclusion body myositis in Japan

Background: Sporadic inclusion body myositis (sIBM) is the most prevalent acquired muscle disease in the elderly. sIBM is an intractable and progressive disease of unknown cause and without effective treatment. The etiology of sIBM is still unknown; however, genetic factors, aging, lifestyles, and environmental factors may be involved. The purpose of this study is to elucidate the cross-sectional profile of patients affected by sIBM in Japan. Methods: We surveyed patient data for 146 cases diagnosed at a number of centers across Japan. We also issued a questionnaire for 67 patients and direct caregivers to further elucidate the natural history of the disease. Results: The mean age at the onset was 63.4 ± 9.2 years. The mean length of time from the onset to diagnosis was 55.52 ± 49.72 months, suggesting that there is a difficulty in diagnosing this disease with long-term consequences because of late treatment. 73 % described the psychological/mental aspect of the disease. The most popular primary caregiver was the patient’s spouse and 57 % patients mentioned that they were having problems managing the finances. Conclusions: Through these surveys, we described the cross-sectional profiles of sIBM in Japan. Many patients described psychological/mental and financial anxiety because of the aged profile of sIBM patients. The profiles of sIBM patients are similar to those in Western countries

The updated retrospective questionnaire study of sporadic inclusion body myositis in Japan

Background: Sporadic inclusion body myositis (sIBM) is the most prevalent muscle disease in elderly people, affecting the daily activities. sIBM is progressive with unknown cause and without effective treatment. In 2015, sIBM was classified as an intractable disease by the Japanese government, and the treatment cost was partly covered by the government. This study aimed to examine the changes in the number of patients with sIBM over the last 10 years and to elucidate the cross-sectional profile of Japanese patients with sIBM. Methods: The number of sIBM patients was estimated through a reply-paid postcard questionnaire for attending physicians. Only patients diagnosed as “definite” or “probable” sIBM by clinical and biopsy sIBM criteria were included in this study (Lancet Neurol 6:620-631, 2007, Neuromuscul Disord 23:1044-1055, 2013). Additionally, a registered selfadministered questionnaire was also sent to 106 patients who agreed to reply via their attending physician, between November 2016 and March 2017. Results: The number of patients diagnosed with sIBM for each 5-year period was 286 and 384 in 2011 and 2016, respectively. Inability to stand-up, cane-dependent gait, inability to open a plastic bottle, choking on food ingestion, and being wheelchair-bound should be included as sIBM milestones. Eight patients were positive for anti-hepatitis C virus antibody; three of them were administered interferon before sIBM onset. Steroids were administered to 33 patients (31.1%) and intravenous immunoglobulin to 46 patients (43.4%). From 2016 to 2017, total of 70 patients applied for the designated incurable disease medical expenses subsidy program. Although the treatment cost was partly covered by the government, many patients expressed psychological/mental and financial anxieties. Conclusions: We determined the cross-sectional profile of Japanese patients with sIBM. Continuous support and prospective surveys are warranted

Identification of helicobacter pylori infection in symptomatic patients in Surabaya, Indonesia, using five diagnostic tests

The prevalence of Helicobacter pylori infection in Indonesia is controversial. We examined the H. pylori infection rate in 78 patients in a hospital in Surabaya using five different tests, including culture, histology, immunohistochemistry, rapid urease test, and urine antibody test. Furthermore, we analysed virulence factors in H. pylori strains from Indonesia. The H. pylori infection rate was only 11·5 in all patients studied, and 2·3 of Javanese patients and 18·0 of Chinese patients were infected (P = 0·01). Although severe gastritis was not observed, activity and inflammation were significantly higher in patients positive for H. pylori than in patients negative for H. pylori. Among genotypes identified from five isolated strains, cagA was found in four; two were vacA s1m1. All cagA-positive strains were oipA 'on' and iceA1 positive. We confirmed both a low H. pylori infection rate and a low prevalence of precancerous lesions in dyspeptic patients in a Surabaya hospital, which may contribute to the low incidence of gastric cancer in Indonesia. © 2014 Cambridge University Press

Guidance for peptide vaccines for the treatment of cancer

Recent progress in fundamental understanding of tumor immunology has opened a new avenue of cancer vaccines. Currently, the development of new cancer vaccines is a global topic and has attracted attention as one of the most important issues in Japan. There is an urgent need for the development of guidance for cancer vaccine clinical studies in order to lead to drug development. Peptide vaccines characteristically have the effect of indirectly acting against cancer through the immune system - a mechanism of action that clearly differs from anticancer drugs that exert a direct effect. Thus, the clinical development of cancer peptide vaccines should be planned and implemented based on the mechanism of action, which differs significantly from conventional anticancer drug research. The Japanese Society for Biological Therapy has created and published Guidance for peptide vaccines for the treatment of cancer as part of its mission and responsibilities towards cancer peptide vaccine development, which is now pursued globally. We welcome comments from regulators and business people as well as researchers in this area. Guidance for Peptide Cancer Vaccines