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Tsuda M, Watanabe Y, Oikawa R, Watanabe R, Higashino M, Kubo K, Yamamoto H, Itoh F, Kato M. Clinical evaluation of a novel molecular diagnosis kit for detecting Helicobacter pylori and clarithromycin-resistant using intragastric fluid. Helicobacter 2022; 27:e12933. [PMID: 36263754 PMCID: PMC9788249 DOI: 10.1111/hel.12933] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 09/23/2022] [Accepted: 09/27/2022] [Indexed: 12/30/2022]
Abstract
BACKGROUND Although there are many Helicobacter pylori (H. pylori) diagnostic methods, the culture and antibiotic susceptibility test is an important method for selecting the most effective H. pylori eradication regimen. However, this diagnostic method is complicated and takes several days; therefore, the development of a rapid and simple diagnostic method is required. Eradication failure due to clarithromycin (CAM) resistance should also be considered. In this study, we report the clinical evaluation of point-of-care testing (POCT) kit using intragastric fluid, a novel kit for detecting H. pylori and CAM resistance. MATERIALS AND METHODS The study participants were 143 patients suspected of H. pylori infection and had an endoscopic examination. The novel diagnostic kit diagnosed H. pylori infection and CAM resistance-associated mutation using intragastric fluid. To diagnose H. pylori infection, the relationship between the diagnostic kit and conventional diagnostic methods (urea breath test, stool antigen test, culture test, and real-time polymerase chain reaction [PCR]) was evaluated. For CAM resistance-associated mutation detection, the concordance between the diagnostic kit and antibiotic susceptibility test was evaluated. RESULTS The diagnosis of H. pylori infection with the novel molecular diagnostic kit using intragastric fluid showed significant relationship with conventional diagnostic methods. Especially when the culture was control, the sensitivity was 100% (67/67), the specificity was 95.9% (71/74), and the overall concordance was 97.9% (138/141). The detection of CAM resistance-associated mutations had a concordance rate of 97.0% (65/67) when compared with the antibiotic susceptibility test. CONCLUSIONS The H. pylori molecular POCT kit uses intragastric fluid as a sample and can diagnose H. pylori infection and detect CAM resistance-associated mutations within an hour. This novel kit is expected to prove useful in selecting the most effective eradication regimen for H. pylori.
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Affiliation(s)
- Momoko Tsuda
- Department of GastroenterologyNational Hospital Organization Hakodate National HospitalHakodateJapan
| | - Yoshiyuki Watanabe
- Department of Internal MedicineKawasaki Rinko General HospitalKawasakiJapan
- Division of Gastroenterology, Department of Internal MedicineSt. Marianna University School of MedicineKawasakiJapan
| | - Ritsuko Oikawa
- Division of Gastroenterology, Department of Internal MedicineSt. Marianna University School of MedicineKawasakiJapan
| | - Ryosuke Watanabe
- Department of GastroenterologyNational Hospital Organization Hakodate National HospitalHakodateJapan
| | - Masayuki Higashino
- Department of GastroenterologyNational Hospital Organization Hakodate National HospitalHakodateJapan
| | - Kimitoshi Kubo
- Department of GastroenterologyNational Hospital Organization Hakodate National HospitalHakodateJapan
| | - Hiroyuki Yamamoto
- Division of Gastroenterology, Department of Internal MedicineSt. Marianna University School of MedicineKawasakiJapan
- Department of BioinformaticsSt. Marianna University Graduate School of MedicineKawasakiJapan
| | - Fumio Itoh
- Division of Gastroenterology, Department of Internal MedicineSt. Marianna University School of MedicineKawasakiJapan
| | - Mototsugu Kato
- Department of GastroenterologyNational Hospital Organization Hakodate National HospitalHakodateJapan
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Abd El Hameed YF, Boghdadi AM, Ghobrial CM, Hassan MA. Association of Helicobacter pylori and parasitic infections in childhood: impact on clinical manifestations and implications. J Parasit Dis 2021; 45:790-796. [PMID: 34475661 DOI: 10.1007/s12639-021-01362-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 02/05/2021] [Indexed: 11/28/2022] Open
Abstract
The association of Helicobacter pylori (H. pylori) infection and parasitic infections including Giardia lamblia (G. lamblia), especially in childhood, is widely recognized to be high in developing communities. We aimed to study the impact of concomitant intestinal parasitic and H. pylori infections on the different clinical presentation of infected children and whether this coinfection could in turn cause any alteration in the clinical manifestations of each other. This cross-sectional study included 150 children of both sexes with their age ranging from 1 to 15 years, having gastrointestinal complaints, throughout 8 months duration. All cases were subjected to full history taking, clinical examination and stool analysis by direct wet smear and formalin-ethyl acetate concentration technique, permanent staining with cold acid fast stain in addition to H. pylori coproantigen detection in stool. Parasitic infection was recorded in 58.6% of patients, with G. lamblia the most detected parasite (35.2%). Cases infected with H. pylori were 63 cases (42%) of which 61.9% of cases showed associated parasitic infection. Diarrhea was the most frequent complaint (63.2%) in cases infected with intestinal parasites, while it was less frequently recorded in co-infected cases (35.8%) and in cases with H. pylori infection only (29.1%) (P value 0.0008). On the other hand, vomiting was less recorded in coinfected cases than cases with H. pylori infection. Coinfection with intestinal parasites (including G. lamblia) and H. pylori could modulate the clinical manifestation of each other especially diarrhea in parasitic infections and vomiting in H. pylori infection.
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Affiliation(s)
- Yasmin F Abd El Hameed
- Department of Medical Parasitology, Kasr Al Ainy Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Abdallah M Boghdadi
- Department of Medical Parasitology, Kasr Al Ainy Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Carolyne M Ghobrial
- Department of Pediatrics, Kasr Al Ainy Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Marwa A Hassan
- Department of Medical Parasitology, Kasr Al Ainy Faculty of Medicine, Cairo University, Cairo, Egypt
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Yonezawa H, Motegi M, Oishi A, Hojo F, Higashi S, Nozaki E, Oka K, Takahashi M, Osaki T, Kamiya S. Lantibiotics Produced by Oral Inhabitants as a Trigger for Dysbiosis of Human Intestinal Microbiota. Int J Mol Sci 2021; 22:3343. [PMID: 33805848 PMCID: PMC8037337 DOI: 10.3390/ijms22073343] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 03/16/2021] [Accepted: 03/22/2021] [Indexed: 12/28/2022] Open
Abstract
Lantibiotics are a type of bacteriocin produced by Gram-positive bacteria and have a wide spectrum of Gram-positive antimicrobial activity. In this study, we determined that Mutacin I/III and Smb (a dipeptide lantibiotic), which are mainly produced by the widespread cariogenic bacterium Streptococcus mutans, have strong antimicrobial activities against many of the Gram-positive bacteria which constitute the intestinal microbiota. These lantibiotics also demonstrate resistance to acid and temperature. Based on these features, we predicted that lantibiotics may be able to persist into the intestinal tract maintaining a strong antimicrobial activity, affecting the intestinal microbiota. Saliva and fecal samples from 69 subjects were collected to test this hypothesis and the presence of lantibiotics and the composition of the intestinal microbiota were examined. We demonstrate that subjects possessing lantibiotic-producing bacteria in their oral cavity exhibited a tendency of decreased species richness and have significantly reduced abundance of the phylum Firmicutes in their intestinal microbiota. Similar results were obtained in the fecal microbiota of mice fed with S. mutans culture supernatant containing the lantibiotic bacteriocin Mutacin I. These results showed that lantibiotic bacteriocins produced in the oral cavity perturb the intestinal microbiota and suggest that oral bacteria may be one of the causative factors of intestinal microbiota dysbiosis.
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Affiliation(s)
- Hideo Yonezawa
- Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo 181-8611, Japan; (M.T.); (T.O.); (S.K.)
| | - Mizuho Motegi
- Division of Oral Restitution, Department of Pediatric Dentistry, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8510, Japan; (M.M.); (A.O.)
| | - Atsushi Oishi
- Division of Oral Restitution, Department of Pediatric Dentistry, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8510, Japan; (M.M.); (A.O.)
| | - Fuhito Hojo
- Institute of Laboratory Animals, Graduate School of Medicine, Kyorin University School of Medicine, Tokyo 181-8611, Japan;
| | - Seiya Higashi
- Central Research Institute, Miyarisan Pharmaceutical Co. Ltd., Tokyo 114-0016, Japan; (S.H.); (K.O.)
| | - Eriko Nozaki
- Core Laboratory for Proteomics and Genomics, Kyorin University School of Medicine, Tokyo 181-8611, Japan;
| | - Kentaro Oka
- Central Research Institute, Miyarisan Pharmaceutical Co. Ltd., Tokyo 114-0016, Japan; (S.H.); (K.O.)
| | - Motomichi Takahashi
- Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo 181-8611, Japan; (M.T.); (T.O.); (S.K.)
- Central Research Institute, Miyarisan Pharmaceutical Co. Ltd., Tokyo 114-0016, Japan; (S.H.); (K.O.)
| | - Takako Osaki
- Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo 181-8611, Japan; (M.T.); (T.O.); (S.K.)
| | - Shigeru Kamiya
- Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo 181-8611, Japan; (M.T.); (T.O.); (S.K.)
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Best LMJ, Takwoingi Y, Siddique S, Selladurai A, Gandhi A, Low B, Yaghoobi M, Gurusamy KS. Non-invasive diagnostic tests for Helicobacter pylori infection. Cochrane Database Syst Rev 2018; 3:CD012080. [PMID: 29543326 PMCID: PMC6513531 DOI: 10.1002/14651858.cd012080.pub2] [Citation(s) in RCA: 90] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND Helicobacter pylori (H pylori) infection has been implicated in a number of malignancies and non-malignant conditions including peptic ulcers, non-ulcer dyspepsia, recurrent peptic ulcer bleeding, unexplained iron deficiency anaemia, idiopathic thrombocytopaenia purpura, and colorectal adenomas. The confirmatory diagnosis of H pylori is by endoscopic biopsy, followed by histopathological examination using haemotoxylin and eosin (H & E) stain or special stains such as Giemsa stain and Warthin-Starry stain. Special stains are more accurate than H & E stain. There is significant uncertainty about the diagnostic accuracy of non-invasive tests for diagnosis of H pylori. OBJECTIVES To compare the diagnostic accuracy of urea breath test, serology, and stool antigen test, used alone or in combination, for diagnosis of H pylori infection in symptomatic and asymptomatic people, so that eradication therapy for H pylori can be started. SEARCH METHODS We searched MEDLINE, Embase, the Science Citation Index and the National Institute for Health Research Health Technology Assessment Database on 4 March 2016. We screened references in the included studies to identify additional studies. We also conducted citation searches of relevant studies, most recently on 4 December 2016. We did not restrict studies by language or publication status, or whether data were collected prospectively or retrospectively. SELECTION CRITERIA We included diagnostic accuracy studies that evaluated at least one of the index tests (urea breath test using isotopes such as 13C or 14C, serology and stool antigen test) against the reference standard (histopathological examination using H & E stain, special stains or immunohistochemical stain) in people suspected of having H pylori infection. DATA COLLECTION AND ANALYSIS Two review authors independently screened the references to identify relevant studies and independently extracted data. We assessed the methodological quality of studies using the QUADAS-2 tool. We performed meta-analysis by using the hierarchical summary receiver operating characteristic (HSROC) model to estimate and compare SROC curves. Where appropriate, we used bivariate or univariate logistic regression models to estimate summary sensitivities and specificities. MAIN RESULTS We included 101 studies involving 11,003 participants, of which 5839 participants (53.1%) had H pylori infection. The prevalence of H pylori infection in the studies ranged from 15.2% to 94.7%, with a median prevalence of 53.7% (interquartile range 42.0% to 66.5%). Most of the studies (57%) included participants with dyspepsia and 53 studies excluded participants who recently had proton pump inhibitors or antibiotics.There was at least an unclear risk of bias or unclear applicability concern for each study.Of the 101 studies, 15 compared the accuracy of two index tests and two studies compared the accuracy of three index tests. Thirty-four studies (4242 participants) evaluated serology; 29 studies (2988 participants) evaluated stool antigen test; 34 studies (3139 participants) evaluated urea breath test-13C; 21 studies (1810 participants) evaluated urea breath test-14C; and two studies (127 participants) evaluated urea breath test but did not report the isotope used. The thresholds used to define test positivity and the staining techniques used for histopathological examination (reference standard) varied between studies. Due to sparse data for each threshold reported, it was not possible to identify the best threshold for each test.Using data from 99 studies in an indirect test comparison, there was statistical evidence of a difference in diagnostic accuracy between urea breath test-13C, urea breath test-14C, serology and stool antigen test (P = 0.024). The diagnostic odds ratios for urea breath test-13C, urea breath test-14C, serology, and stool antigen test were 153 (95% confidence interval (CI) 73.7 to 316), 105 (95% CI 74.0 to 150), 47.4 (95% CI 25.5 to 88.1) and 45.1 (95% CI 24.2 to 84.1). The sensitivity (95% CI) estimated at a fixed specificity of 0.90 (median from studies across the four tests), was 0.94 (95% CI 0.89 to 0.97) for urea breath test-13C, 0.92 (95% CI 0.89 to 0.94) for urea breath test-14C, 0.84 (95% CI 0.74 to 0.91) for serology, and 0.83 (95% CI 0.73 to 0.90) for stool antigen test. This implies that on average, given a specificity of 0.90 and prevalence of 53.7% (median specificity and prevalence in the studies), out of 1000 people tested for H pylori infection, there will be 46 false positives (people without H pylori infection who will be diagnosed as having H pylori infection). In this hypothetical cohort, urea breath test-13C, urea breath test-14C, serology, and stool antigen test will give 30 (95% CI 15 to 58), 42 (95% CI 30 to 58), 86 (95% CI 50 to 140), and 89 (95% CI 52 to 146) false negatives respectively (people with H pylori infection for whom the diagnosis of H pylori will be missed).Direct comparisons were based on few head-to-head studies. The ratios of diagnostic odds ratios (DORs) were 0.68 (95% CI 0.12 to 3.70; P = 0.56) for urea breath test-13C versus serology (seven studies), and 0.88 (95% CI 0.14 to 5.56; P = 0.84) for urea breath test-13C versus stool antigen test (seven studies). The 95% CIs of these estimates overlap with those of the ratios of DORs from the indirect comparison. Data were limited or unavailable for meta-analysis of other direct comparisons. AUTHORS' CONCLUSIONS In people without a history of gastrectomy and those who have not recently had antibiotics or proton ,pump inhibitors, urea breath tests had high diagnostic accuracy while serology and stool antigen tests were less accurate for diagnosis of Helicobacter pylori infection.This is based on an indirect test comparison (with potential for bias due to confounding), as evidence from direct comparisons was limited or unavailable. The thresholds used for these tests were highly variable and we were unable to identify specific thresholds that might be useful in clinical practice.We need further comparative studies of high methodological quality to obtain more reliable evidence of relative accuracy between the tests. Such studies should be conducted prospectively in a representative spectrum of participants and clearly reported to ensure low risk of bias. Most importantly, studies should prespecify and clearly report thresholds used, and should avoid inappropriate exclusions.
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Affiliation(s)
- Lawrence MJ Best
- Royal Free Campus, UCL Medical SchoolDepartment of SurgeryRowland Hill StreetLondonUKNW32PF
| | - Yemisi Takwoingi
- University of BirminghamInstitute of Applied Health ResearchEdgbastonBirminghamUKB15 2TT
| | | | | | | | | | - Mohammad Yaghoobi
- McMaster University and McMaster University Health Sciences CentreDivision of Gastroenterology1200 Main Street WestHamiltonONCanada
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Osaki T, Zaman C, Yonezawa H, Lin Y, Okuda M, Nozaki E, Hojo F, Kurata S, Hanawa T, Kikuchi S, Kamiya S. Influence of Intestinal Indigenous Microbiota on Intrafamilial Infection by Helicobacter pylori in Japan. Front Immunol 2018. [PMID: 29515585 PMCID: PMC5826345 DOI: 10.3389/fimmu.2018.00287] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Helicobacter pylori is a causative pathogen of chronic gastritis, gastric ulcer disease, and gastric cancer. Humans are known to be a natural host for H. pylori and tend to acquire the pathogen before the age of 5 years. The infection may then persist lifelong if eradication therapy is not applied. One of the modes of transmission of H. pylori is between family members, and therefore, the presence of infected family members is an important risk factor in children. However, other environmental factors have not been fully analyzed. The present study was performed to clarify whether and to what extent intestinal microbiota affect H. pylori intrafamilial infection. The fecal specimens from H. pylori-infected infants and H. pylori-infected and non-infected family members were collected in cohort studies conducted by Sasayama City, Hyogo Prefecture from 2010 to 2013. In total, 18 fecal DNA from 5 families were analyzed. Samples were amplified using 16S rRNA universal primers, and the amplicons were sequenced using the Ion PGM system. Principal-coordinate analysis demonstrated that there was no difference in intestinal microbiota between H. pylori-positive and H. pylori-negative groups. In intrafamilial comparison tests, the Manhattan distance of intestinal microbiota between the H. pylori-infected infant proband and H. pylori-negative mother was nearest in the family with low intestinal microbial diversity. However, in the family with the highest intestinal microbial diversity, the nearest Manhattan distance was shown between the H. pylori-infected infant proband and H. pylori-infected mother. The results in this study showed that the composition of the intestinal microbiota was very similar between members of the same family, and as such, colonization with organisms highly similar to the infected parent(s) may be a risk factor for H. pylori infection in children.
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Affiliation(s)
- Takako Osaki
- Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan
| | - Cynthia Zaman
- Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan
| | - Hideo Yonezawa
- Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan
| | - Yingsong Lin
- Department of Public Health, Aichi Medical University School of Medicine, Aichi, Japan
| | - Masumi Okuda
- Department of Pediatrics, Aichi Medical University School of Medicine, Aichi, Japan.,Department of General Medicine and Community Health Science, Hyogo College of Medicine, Hyogo, Japan
| | - Eriko Nozaki
- Core Laboratory for Proteomics and Genomics, Kyorin University School of Medicine, Tokyo, Japan
| | - Fuhito Hojo
- Graduate School of Medicine, Institute of Laboratory Animals, Kyorin University, Tokyo, Japan
| | - Satoshi Kurata
- Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan
| | - Tomoko Hanawa
- Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan
| | - Shogo Kikuchi
- Department of Public Health, Aichi Medical University School of Medicine, Aichi, Japan
| | - Shigeru Kamiya
- Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan
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6
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Khadangi F, Yassi M, Kerachian MA. Review: Diagnostic accuracy of PCR-based detection tests for Helicobacter Pylori in stool samples. Helicobacter 2017; 22. [PMID: 28961384 DOI: 10.1111/hel.12444] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Although different methods have been established to detect Helicobacter pylori (H. pylori) infection, identifying infected patients is an ongoing challenge. The aim of this meta-analysis was to provide pooled diagnostic accuracy measures for stool PCR test in the diagnosis of H. pylori infection. METHODS In this study, a systematic review and meta-analysis were carried out on various sources, including MEDLINE, Web of Sciences, and the Cochrane Library from April 1, 1999, to May 1, 2016. This meta-analysis adheres to the guidelines provided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses report (PRISMA Statement). The clinical value of DNA stool PCR test was based on the pooled false positive, false negative, true positive, and true negative of different genes. RESULTS Twenty-six of 328 studies identified met the eligibility criteria. Stool PCR test had a performance of 71% (95% CI: 68-73) sensitivity, 96% (95% CI: 94-97) specificity, and 65.6 (95% CI: 30.2-142.5) diagnostic odds ratio (DOR) in diagnosis of H. pylori. The DOR of genes which showed the highest performance of stool PCR tests was as follows: 23S rRNA 152.5 (95% CI: 55.5-418.9), 16S rRNA 67.9 (95%CI: 6.4-714.3), and glmM 68.1 (95%CI: 20.1-231.7). CONCLUSIONS The sensitivity and specificity of stool PCR test are relatively in the same spectrum of other diagnostic methods for the detection of H. pylori infection. In descending order of significance, the most diagnostic candidate genes using PCR detection were 23S rRNA, 16S rRNA, and glmM. PCR for 23S rRNA gene which has the highest performance could be applicable to detect H. pylori infection.
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Affiliation(s)
- Fatemeh Khadangi
- Cancer Genetics Research Unit, Reza Radiotherapy and Oncology Center, Mashhad, Iran
| | - Maryam Yassi
- Cancer Genetics Research Unit, Reza Radiotherapy and Oncology Center, Mashhad, Iran
| | - Mohammad Amin Kerachian
- Cancer Genetics Research Unit, Reza Radiotherapy and Oncology Center, Mashhad, Iran.,Cancer Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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7
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Osaki T, Mabe K, Zaman C, Yonezawa H, Okuda M, Amagai K, Fujieda S, Goto M, Shibata W, Kato M, Kamiya S. Usefulness of detection of clarithromycin-resistant Helicobacter pylori from fecal specimens for young adults treated with eradication therapy. Helicobacter 2017; 22. [PMID: 28544222 DOI: 10.1111/hel.12396] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND To prevent Helicobacter pylori infection in the younger generation, it is necessary to investigate the prevalence of antibiotic-resistant H. pylori. OBJECTIVE The aim of this study was to evaluate the method of PCR-based sequencing to detect clarithromycin (CAM) resistance-associated mutations using fecal samples as a noninvasive method. METHODS DNA extracted from fecal specimens and isolates from gastric biopsy specimens were collected from patients with H. pylori infection. Antibiotic resistance to CAM was analyzed by molecular and culture methods. The detection rates of CAM resistance-associated mutations (A2142C or A2143G) were compared before and after eradication therapy. RESULTS With CAM resistance of H. pylori evaluated by antibiotic susceptibility test as a gold standard, the sensitivity and the specificity of gene mutation detection from fecal DNA were 80% and 84.8%, respectively. In contrast, using DNA of isolated strains, the sensitivity and the specificity were 80% and 100%. Of the seven cases in which eradication was unsuccessful by triple therapy including CAM, CAM-resistant H. pylori, and resistance-associated mutations were detected in three cases, CAM-resistant H. pylori without the mutation was detected in two patients, and resistance-associated mutation was only detected in one patient. CONCLUSION PCR-based sequencing to detect CAM resistance-associated mutations using isolates or fecal samples was useful for finding antibiotic-resistant H. pylori infection. Although the specificity of the detection from fecal samples compared with antibiotic susceptibility testing was lower than that from isolates, this fecal detection method is suitable especially for asymptomatic subjects including children. Further improvement is needed before clinical application.
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Affiliation(s)
- Takako Osaki
- Department of Infectious Diseases, Kyorin University School of Medicine, Mitaka, Tokyo, Japan
| | - Katsuhiro Mabe
- Department of Gastroenterology, National Hospital Organization Hakodate Hospital, Hakodate, Japan.,Division of Endoscopy, Hokkaido University Hospital, Sapporo, Japan
| | - Cynthia Zaman
- Department of Infectious Diseases, Kyorin University School of Medicine, Mitaka, Tokyo, Japan
| | - Hideo Yonezawa
- Department of Infectious Diseases, Kyorin University School of Medicine, Mitaka, Tokyo, Japan
| | - Masumi Okuda
- Department of General Medicine and Community Health Science, Hyogo College of Medicine, Sasayama, Hyogo, Japan
| | - Kenji Amagai
- Ibaraki Prefectural Central Hospital, Ibaraki, Japan
| | | | | | - Wataru Shibata
- Department of Gastroenterology, Yokohama City University, Yokohama, Japan
| | - Mototsugu Kato
- Department of Gastroenterology, National Hospital Organization Hakodate Hospital, Hakodate, Japan.,Division of Endoscopy, Hokkaido University Hospital, Sapporo, Japan
| | - Shigeru Kamiya
- Department of Infectious Diseases, Kyorin University School of Medicine, Mitaka, Tokyo, Japan
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Joint ESPGHAN/NASPGHAN Guidelines for the Management of Helicobacter pylori in Children and Adolescents (Update 2016). J Pediatr Gastroenterol Nutr 2017; 64:991-1003. [PMID: 28541262 DOI: 10.1097/mpg.0000000000001594] [Citation(s) in RCA: 290] [Impact Index Per Article: 36.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Because of the changing epidemiology of Helicobacter pylori infection and low efficacy of currently recommended therapies, an update of the European Society for Paediatric Gastroenterology Hepatology and Nutrition/North American Society for Pediatric Gastroenterology, Hepatology and Nutrition recommendations for the diagnosis and management of H pylori infection in children and adolescents is required. METHODS A systematic review of the literature (time period: 2009-2014) was performed. Representatives of both societies evaluated the quality of evidence using GRADE (Grading of Recommendation Assessment, Development, and Evaluation) to formulate recommendations, which were voted upon and finalized using a Delphi process and face-to-face meeting. RESULTS The consensus group recommended that invasive diagnostic testing for H pylori be performed only when treatment will be offered if tests are positive. To reach the aim of a 90% eradication rate with initial therapy, antibiotics should be tailored according to susceptibility testing. Therapy should be administered for 14 days, emphasizing strict adherence. Clarithromycin-containing regimens should be restricted to children infected with susceptible strains. When antibiotic susceptibility profiles are not known, high-dose triple therapy with proton pump inhibitor, amoxicillin, and metronidazole for 14 days or bismuth-based quadruple therapy is recommended. Success of therapy should be monitored after 4 to 8 weeks by reliable noninvasive tests. CONCLUSIONS The primary goal of clinical investigation is to identify the cause of upper gastrointestinal symptoms rather than H pylori infection. Therefore, we recommend against a test and treat strategy. Decreasing eradication rates with previously recommended treatments call for changes to first-line therapies and broader availability of culture or molecular-based testing to tailor treatment to the individual child.
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Wang YK, Kuo FC, Liu CJ, Wu MC, Shih HY, Wang SSW, Wu JY, Kuo CH, Huang YK, Wu DC. Diagnosis of Helicobacter pylori infection: Current options and developments. World J Gastroenterol 2016. [PMID: 26523098 DOI: 10.3748/wjg.v21.i40.11221.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/11/2022] Open
Abstract
Accurate diagnosis of Helicobacter pylori (H. pylori) infection is a crucial part in the effective management of many gastroduodenal diseases. Several invasive and non-invasive diagnostic tests are available for the detection of H. pylori and each test has its usefulness and limitations in different clinical situations. Although none can be considered as a single gold standard in clinical practice, several techniques have been developed to give the more reliable results. Invasive tests are performed via endoscopic biopsy specimens and these tests include histology, culture, rapid urease test as well as molecular methods. Developments of endoscopic equipment also contribute to the real-time diagnosis of H. pylori during endoscopy. Urea breathing test and stool antigen test are most widely used non-invasive tests, whereas serology is useful in screening and epidemiological studies. Molecular methods have been used in variable specimens other than gastric mucosa. More than detection of H. pylori infection, several tests are introduced into the evaluation of virulence factors and antibiotic sensitivity of H. pylori, as well as screening precancerous lesions and gastric cancer. The aim of this article is to review the current options and novel developments of diagnostic tests and their applications in different clinical conditions or for specific purposes.
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Affiliation(s)
- Yao-Kuang Wang
- Yao-Kuang Wang, Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 812, Taiwan
| | - Fu-Chen Kuo
- Yao-Kuang Wang, Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 812, Taiwan
| | - Chung-Jung Liu
- Yao-Kuang Wang, Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 812, Taiwan
| | - Meng-Chieh Wu
- Yao-Kuang Wang, Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 812, Taiwan
| | - Hsiang-Yao Shih
- Yao-Kuang Wang, Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 812, Taiwan
| | - Sophie S W Wang
- Yao-Kuang Wang, Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 812, Taiwan
| | - Jeng-Yih Wu
- Yao-Kuang Wang, Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 812, Taiwan
| | - Chao-Hung Kuo
- Yao-Kuang Wang, Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 812, Taiwan
| | - Yao-Kang Huang
- Yao-Kuang Wang, Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 812, Taiwan
| | - Deng-Chyang Wu
- Yao-Kuang Wang, Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 812, Taiwan
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Zhang Y, Bao H, Miao F, Peng Y, Shen Y, Gu W, Meng Q, Wang W, Zhang J. Production and application of polyclonal and monoclonal antibodies against Spiroplasma eriocheiris. Sci Rep 2015; 5:17871. [PMID: 26639364 PMCID: PMC4671143 DOI: 10.1038/srep17871] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Accepted: 11/06/2015] [Indexed: 11/09/2022] Open
Abstract
A new species of spiroplasma, Spiroplasma eriocheiris (S. eriocheiris), was identified as a lethal pathogen of tremor disease (TD) in Chinese mitten crab recently. In order to acquire appropriate biological and diagnostic tools for characterizing this newly discovered pathogen, 5 monoclonal antibodies (mAbs) and a polyclonal antibody (pAb) against S. eriocheiris were produced. Among the mAbs, 6F5, 7C8 and 12H5 lead to the deformation of S. eriocheiris. A peptide sequence, YMRDMQSGLPRY was identified as a mimic motif of MreB that is the cell shape determining protein of S. eriocheiris interacting with 3 mAbs. Furthermore, a double antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) for detection of S. eriocheiris was established using the mAb and pAb we prepared. It detected as low as 0.1 μg/mL of S. eriocheiris. No cross-reaction was observed with three other common bacteria (Pseudomonas aeruginosa, Escherichia coli, and Bacillus subtilis) and the hemolymph samples of healthy Eriocheir sinensis. Collectively, our results indicated that the mAbs and pAb we prepared could be used in the analysis of S. eriocheiris membrane proteins mimotope and development of a diagnostic kit for S. eriocheiris infections.
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Affiliation(s)
- Ying Zhang
- Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Department of Microbiology and Immunology, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing 210009, China
| | - Haixun Bao
- Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Department of Microbiology and Immunology, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing 210009, China
| | - Fengqin Miao
- Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Department of Microbiology and Immunology, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing 210009, China
| | - Yaqin Peng
- Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Department of Microbiology and Immunology, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing 210009, China
| | - Yuqing Shen
- Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Department of Microbiology and Immunology, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing 210009, China
| | - Wei Gu
- Jiangsu Key Laboratory for Biodiversity &Biotechnology and Jiangsu Key Laboratory for Aquatic Crustacean Diseases, College of Life Sciences, Nanjing Normal University, 1 Wenyuan Road, Nanjing 210023, China
| | - Qingguo Meng
- Jiangsu Key Laboratory for Biodiversity &Biotechnology and Jiangsu Key Laboratory for Aquatic Crustacean Diseases, College of Life Sciences, Nanjing Normal University, 1 Wenyuan Road, Nanjing 210023, China
| | - Wen Wang
- Jiangsu Key Laboratory for Biodiversity &Biotechnology and Jiangsu Key Laboratory for Aquatic Crustacean Diseases, College of Life Sciences, Nanjing Normal University, 1 Wenyuan Road, Nanjing 210023, China
| | - Jianqiong Zhang
- Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Department of Microbiology and Immunology, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing 210009, China
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Wang YK, Kuo FC, Liu CJ, Wu MC, Shih HY, Wang SSW, Wu JY, Kuo CH, Huang YK, Wu DC. Diagnosis of Helicobacter pylori infection: Current options and developments. World J Gastroenterol 2015; 21:11221-11235. [PMID: 26523098 PMCID: PMC4616200 DOI: 10.3748/wjg.v21.i40.11221] [Citation(s) in RCA: 232] [Impact Index Per Article: 23.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 08/06/2015] [Accepted: 09/28/2015] [Indexed: 02/06/2023] Open
Abstract
Accurate diagnosis of Helicobacter pylori (H. pylori) infection is a crucial part in the effective management of many gastroduodenal diseases. Several invasive and non-invasive diagnostic tests are available for the detection of H. pylori and each test has its usefulness and limitations in different clinical situations. Although none can be considered as a single gold standard in clinical practice, several techniques have been developed to give the more reliable results. Invasive tests are performed via endoscopic biopsy specimens and these tests include histology, culture, rapid urease test as well as molecular methods. Developments of endoscopic equipment also contribute to the real-time diagnosis of H. pylori during endoscopy. Urea breathing test and stool antigen test are most widely used non-invasive tests, whereas serology is useful in screening and epidemiological studies. Molecular methods have been used in variable specimens other than gastric mucosa. More than detection of H. pylori infection, several tests are introduced into the evaluation of virulence factors and antibiotic sensitivity of H. pylori, as well as screening precancerous lesions and gastric cancer. The aim of this article is to review the current options and novel developments of diagnostic tests and their applications in different clinical conditions or for specific purposes.
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Abstract
This review includes the main pediatric studies published from April 2014 to March 2015. The host response of Treg cells with increases in FOXP3 and TGF-β1 combined with a reduction in IFN-γ by Teff cells may contribute to Helicobacter pylori susceptibility in children. Genotypic variability in H. pylori strains influences the clinical manifestation of the infection. Helicobacter pylori infection is associated with variables indicative of a crowded environment and poor living conditions, while breast-feeding has a protective effect. Intrafamilial infection, especially from mother to children and from sibling to sibling, is the dominant transmission route. Studies showed conflicting results regarding the association between H. pylori infection and iron deficiency anemia. One study suggests that H. pylori eradication plays a role in the management of chronic immune thrombocytopenic purpura in H. pylori-infected children and adolescents. The prevalence of H. pylori was higher in chronic urticaria patients than in controls and, following H. pylori eradication, urticarial symptoms disappeared. An inverse relationship between H. pylori infection and allergic disease was reported. Antibiotic resistance and insufficient compliance to treatment limit the efficacy of eradication therapy. Sequential therapy had no advantage over standard triple therapy. In countries where H. pylori infection is prevalent, studies focusing on virulence factors and antibiotic susceptibility may provide anticipation of the prognosis and may be helpful to reduce morbidity and mortality.
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Affiliation(s)
- Eleftheria Roma
- First Department of Pediatrics, University of Athens, Athens, Greece
| | - Erasmo Miele
- Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Naples, Italy
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Abstract
Proton pump inhibitors (PPI) are a major cause of false-negative Helicobacter pylori test results. Detecting PPI use and stopping it 2 weeks before testing is the preferred approach to improve the reliability of H pylori diagnostic tests. Immunoblot and molecular methods may be useful for the detection of H pylori infection in difficult cases. When conventional tests are negative and eradication is strongly indicated, empirical H pylori treatment should be considered. In this article, an updated critical review of the usefulness of the various invasive and noninvasive tests in the context of extensive PPI use is provided.
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