|
1
|
Smith SI, Schulz C, Ugiagbe R, Ndip R, Dieye Y, Leja M, Onyekwere C, Ndububa D, Ajayi A, Jolaiya TF, Jaka H, Setshedi M, Gunturu R, Otegbayo JA, Lahbabi-Amrani N, Arigbabu AO, Kayamba V, Nashidengo PA. Helicobacter pylori Diagnosis and Treatment in Africa: The First Lagos Consensus Statement of the African Helicobacter and Microbiota Study Group. Dig Dis 2024; 42:240-256. [PMID: 38493766 DOI: 10.1159/000537878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Accepted: 02/14/2024] [Indexed: 03/19/2024]
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infection is the most prevalent type of bacterial infection. Current guidelines from different regions of the world neglect specific African conditions and requirements. The African Helicobacter and Microbiota Study Group (AHMSG), founded in 2022, aimed to create an Africa-specific consensus report reflecting Africa-specific issues. SUMMARY Eighteen experts from nine African countries and two European delegates supported by nine African collaborators from eight other countries prepared statements on the most important African issues in four working groups: (1) epidemiology, (2) diagnosis, (3) indications and prevention, and (4) treatment. Limited resources, restricted access to medical systems, and underdeveloped diagnostic facilities differ from those of other regions. The results of the individual working groups were presented for the final consensus voting, which included all board members. KEY MESSAGES There is a need for further studies on H. pylori prevalence in Africa, with diagnosis hinged on specific African situation. Treatment of H. pylori in the African setting should be based on accessibility and reimbursement, while indication and prevention should be defined in specific African countries.
Collapse
Affiliation(s)
- Stella I Smith
- Molecular Biology and Biotechnology Department, Nigerian Institute of Medical Research, Lagos, Nigeria
| | - Christian Schulz
- Medical Department II, University Hospital, Ludwig-Maximilians-Universität, Munich, Germany
- DZIF Deutsches Zentrum für Infektionsforschung, Partner Site Munich, Munich, Germany
| | - Rose Ugiagbe
- Department of Medicine, University of Benin Teaching Hospital, Benin, Nigeria
| | - Roland Ndip
- Department of Microbiology and Parasitology, University of Buea, Buea, Cameroon
| | - Yakhya Dieye
- Pole of Microbiology, Institut Pasteur de Dakar, Dakar, Senegal
| | - Marcis Leja
- Faculty of Medicine, University of Latvia, Riga, Latvia
| | - Charles Onyekwere
- Department of Medicine, Lagos State University Teaching Hospital, Ikeja, Nigeria
| | - Dennis Ndububa
- Department of Medicine, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria
| | - Abraham Ajayi
- Molecular Biology and Biotechnology Department, Nigerian Institute of Medical Research, Lagos, Nigeria
| | | | - Hyasinta Jaka
- Department of Internal Medicine, Catholic University of Health and Allied Sciences, Mwanza, Tanzania
| | - Mashiko Setshedi
- Departments of Medicine, Division of Gastroenterology, University of Cape Town, Cape Town, South Africa
| | - Revathi Gunturu
- Department of Pathology, Aga Khan University Hospital, Nairobi, Kenya
| | | | - Naima Lahbabi-Amrani
- Faculty of Medicine and Pharmacy in Rabat, University Mohammed V, Rabat, Morocco
| | | | - Violet Kayamba
- Department of Internal Medicine, University of Zambia School of Medicine, Lusaka, Zambia
| | | |
Collapse
|
|
2
|
Fischbach W, Bornschein J, Hoffmann JC, Koletzko S, Link A, Macke L, Malfertheiner P, Schütte K, Selgrad DM, Suerbaum S, Schulz C. Update S2k-Guideline Helicobacter pylori and gastroduodenal ulcer disease of the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:261-321. [PMID: 38364851 DOI: 10.1055/a-2181-2225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/18/2024]
Affiliation(s)
| | - Jan Bornschein
- Translational Gastroenterology Unit John, John Radcliffe Hospital Oxford University Hospitals, Oxford, United Kingdom
| | - Jörg C Hoffmann
- Medizinische Klinik I, St. Marien- und St. Annastiftskrankenhaus, Ludwigshafen, Deutschland
| | - Sibylle Koletzko
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU-Klinikum Munich, Munich, Deutschland
- Department of Paediatrics, Gastroenterology and Nutrition, School of Medicine Collegium Medicum University of Warmia and Mazury, 10-719 Olsztyn, Poland
| | - Alexander Link
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Magdeburg, Magdeburg, Deutschland
| | - Lukas Macke
- Medizinische Klinik und Poliklinik II Campus Großhadern, Universitätsklinikum Munich, Munich, Deutschland
- Deutsches Zentrum für Infektionsforschung, Standort Munich, Munich, Deutschland
| | - Peter Malfertheiner
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Magdeburg, Magdeburg, Deutschland
- Medizinische Klinik und Poliklinik II Campus Großhadern, Universitätsklinikum Munich, Munich, Deutschland
| | - Kerstin Schütte
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Niels-Stensen-Kliniken Marienhospital Osnabrück, Osnabrück, Deutschland
| | - Dieter-Michael Selgrad
- Medizinische Klinik Gastroenterologie und Onkologie, Klinikum Fürstenfeldbruck, Fürstenfeldbruck, Deutschland
- Klinik für Innere Medizin 1, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Sebastian Suerbaum
- Universität Munich, Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Munich, Deutschland
- Nationales Referenzzentrum Helicobacter pylori, Pettenkoferstr. 9a, 80336 Munich, Deutschland
- Deutsches Zentrum für Infektionsforschung, Standort Munich, Munich, Deutschland
| | - Christian Schulz
- Medizinische Klinik und Poliklinik II Campus Großhadern, Universitätsklinikum Munich, Munich, Deutschland
- Deutsches Zentrum für Infektionsforschung, Standort Munich, Munich, Deutschland
| |
Collapse
|
|
3
|
Alavifard H, Nabavi-Rad A, Baghaei K, Sadeghi A, Yadegar A, Zali MR. Pyrosequencing analysis for rapid and accurate detection of clarithromycin resistance-associated mutations in Iranian Helicobacter pylori isolates. BMC Res Notes 2023; 16:136. [PMID: 37415212 PMCID: PMC10324197 DOI: 10.1186/s13104-023-06420-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Accepted: 06/27/2023] [Indexed: 07/08/2023] Open
Abstract
BACKGROUND Treatment of Helicobacter pylori (H. pylori) infection has become challenging following the development of primary antibiotic resistance. A primary therapeutic regimen for H. pylori eradication includes clarithromycin; however, the presence of point mutations within the 23S rRNA sequence of H. pylori contributes to clarithromycin resistance and eradication failure. Thus, we aimed to develop a rapid and precise method to determine clarithromycin resistance-related point mutations using the pyrosequencing method. METHODS AND RESULTS H. pylori was isolated from 82 gastric biopsy samples and minimal inhibitory concentration (MIC) was evaluated using the agar dilution method. Clarithromycin resistance-associated point mutations were detected by Sanger sequencing, from which 11 isolates were chosen for pyrosequencing. Our results demonstrated a 43.9% (36/82) prevalence in resistance to clarithromycin. The A2143G mutation was detected in 8.3% (4/48) of H. pylori isolates followed by A2142G (6.2%), C2195T (4.1%), T2182C (4.1%), and C2288T (2%). Although the C2195T mutation was only detected by Sanger sequencing, the overall results from pyrosequencing and Sanger sequencing platforms were comparable. CONCLUSIONS Pyrosequencing could be used as a rapid and practical platform in clinical laboratories to determine the susceptibility profile of H. pylori isolates. This might pave the way for efficient H. pylori eradication upon detection.
Collapse
Affiliation(s)
- Helia Alavifard
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Nabavi-Rad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Kaveh Baghaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Sadeghi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
4
|
Autoren, Collaborators:. Aktualisierte S2k-Leitlinie Helicobacter
pylori und gastroduodenale Ulkuskrankheit der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – Juli 2022 – AWMF-Registernummer: 021–001. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:544-606. [PMID: 37146633 DOI: 10.1055/a-1975-0414] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/07/2023]
|
|
5
|
Gareayaghi N, Kocazeybek B. Detection of A2143G, A2142C, and A2142G Point Mutations with Real-Time PCR in Stool Specimens from Children Infected with Helicobacter pylori. Diagnostics (Basel) 2022; 12:2119. [PMID: 36140521 PMCID: PMC9497693 DOI: 10.3390/diagnostics12092119] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 08/26/2022] [Accepted: 08/29/2022] [Indexed: 11/16/2022] Open
Abstract
Reports have indicated an increasing prevalence of clarithromycin resistance in children relative to adults. Thus, it is important to investigate primary clarithromycin resistance before therapy to avoid treatment failure. A2142G, A2143G, and A2142C point mutations in the peptidyltransferase region of the 23S ribosomal RNA (rRNA) of Helicobacter pylori (H. pylori) strains isolated from children with gastrointestinal symptoms and asymptomatic children were evaluated via real-time polymerase chain reaction (RT-PCR) using fecal DNA samples. The presence of H. pylori was determined using a fecal H. pylori antigen enzyme-linked immunosorbent assay (ELISA) kit from the stools of children (n = 543). A2143G, A2142C, and A2142G point mutations were detected via RT-PCR and confirmed by sequencing the 23S rDNA. Fecal H. pylori antigen testing was positive in 101 symptomatic (49) and asymptomatic (52) children. A significant difference was found between the 0-5- and 5-18-year-old groups in terms of the A2143G and A2142G point mutations (p = 0.001). The A2142C mutation was not detected. There was a significant difference in the A2143G mutation between the symptomatic and asymptomatic 5-18-year-old children (p = 0.019). Macrolides are frequently used to treat upper respiratory tract infections in children due to their selective pressure effect. We suggest that H. pylori strains carrying mutations in the 23S RNA subunit conferring clarithromycin resistance may lead to an intense inflammatory response in the gastric epithelial cells, allowing them to proliferate more rapidly and causing possible diarrhea, halitosis, or abdominal pain in children.
Collapse
Affiliation(s)
- Nesrin Gareayaghi
- Istanbul Sisli Hamidiye Etfal Training and Research Hospital, Center for Blood, University of Health Sciences, Istanbul 34098, Turkey
| | - Bekir Kocazeybek
- Department of Medical Microbiology, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul 34098, Turkey
| |
Collapse
|
|
6
|
Alavifard H, Mirzaei N, Yadegar A, Baghaei K, Smith SM, Sadeghi A, Zali MR. Investigation of Clarithromycin Resistance-Associated Mutations and Virulence Genotypes of Helicobacter pylori Isolated from Iranian Population: A Cross-Sectional Study. Curr Microbiol 2021; 78:244-254. [PMID: 33251569 DOI: 10.1007/s00284-020-02295-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 11/11/2020] [Indexed: 12/17/2022]
Abstract
Antibiotic resistance has brought into question the efficiency of clarithromycin which is a vital component of eradication therapy for Helicobacter pylori infection. The point mutations within the 23S rRNA sequence of H. pylori isolates which contribute to clarithromycin resistance have yet to be fully characterized. This study was aimed to detect clarithromycin resistance-associated mutations and assess the prevalence of key virulence factors of H. pylori among Iranian patients. Amplification of 16S rRNA and glmM genes were done to identify H. pylori. Minimal inhibitory concentration (MIC) of clarithromycin in 82 H. pylori clinical isolates was determined by agar dilution method. Subsequently, various virulence markers including cagA, vacA, sabA, babA, and dupA of H. pylori were identified by PCR. PCR-sequencing was applied to detect point mutations in the 23S rRNA gene. Based on MIC values, 43.9% of H. pylori isolates showed resistance to clarithromycin. The babA and cagA genes were detected in 92.7% and 82.9% of isolates, assigned to be higher than other virulence factors. No significant relationship was found between the H. pylori virulence genotypes and clarithromycin susceptibility (P > 0.05). Analyzing the 23S rRNA sequences revealed A2143G (4/48, 8.3%) and A2142G (3/48, 6.2%) as the most prevalent mutations in clarithromycin-resistant isolates. Additionally, several novel mutations including G2220T, C2248T, A2624C, G2287A, T2188C, G2710C, C2248T, G2269A, and G2224T were also detected among either resistant or susceptible isolates. Our findings revealed the presence of several point mutations in the 23S rRNA gene of H. pylori isolates which may be associated with resistance to clarithromycin.
Collapse
Affiliation(s)
- Helia Alavifard
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nasrin Mirzaei
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Kaveh Baghaei
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sinéad Marian Smith
- School of Medicine & School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland
| | - Amir Sadeghi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
7
|
|
|
8
|
Gong Y, Yuan Y. Resistance mechanisms of Helicobacter pylori and its dual target precise therapy. Crit Rev Microbiol 2018; 44:371-392. [PMID: 29293032 DOI: 10.1080/1040841x.2017.1418285] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Helicobacter pylori drug resistance presents a significant challenge to the successful eradication of this pathogen. To find strategies to improve the eradication efficacy of H. pylori, it is necessary to clarify the resistance mechanisms involved. The mechanisms of H. pylori drug resistance can be investigated from two angles: the pathogen and the host. A comprehensive understanding of the molecular mechanisms of H. pylori resistance based on both pathogen and host would aid the implementation of precise therapy, or ideally "dual target precise therapy" (bacteria and host-specific target therapy). In recent years, with increased understanding of the mechanisms of H. pylori resistance, the focus of eradication has shifted from disease-specific to patient-specific treatment. The implementation of "precision medicine" has also provided a new perspective on the treatment of infectious diseases. In this article, we systematically review current research on H. pylori drug resistance from the perspective of both the pathogen and the host. We also review therapeutic strategies targeted to pathogen and host factors that are aimed at achieving precise treatment of H. pylori.
Collapse
Affiliation(s)
- Yuehua Gong
- a Tumor Etiology and Screening Department of Cancer Institute and General Surgery , the First Hospital of China Medical University , Shenyang , China.,b Key Laboratory of Cancer Etiology and Prevention (China Medical University) Liaoning Provincial Education Department , Shenyang , China.,c National Clinical Research Center for Digestive Diseases , Xi'an , China
| | - Yuan Yuan
- a Tumor Etiology and Screening Department of Cancer Institute and General Surgery , the First Hospital of China Medical University , Shenyang , China.,b Key Laboratory of Cancer Etiology and Prevention (China Medical University) Liaoning Provincial Education Department , Shenyang , China.,c National Clinical Research Center for Digestive Diseases , Xi'an , China
| |
Collapse
|
|
9
|
Li Y, Hu X, Ding D, Zou Y, Xu Y, Wang X, Zhang Y, Chen L, Chen Z, Tan W. In situ targeted MRI detection of Helicobacter pylori with stable magnetic graphitic nanocapsules. Nat Commun 2017. [PMID: 28643777 PMCID: PMC5501158 DOI: 10.1038/ncomms15653] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Helicobacter pylori infection is implicated in the aetiology of many diseases. Despite numerous studies, a painless, fast and direct method for the in situ detection of H. pylori remains a challenge, mainly due to the strong acidic/enzymatic environment of the gastric mucosa. Herein, we report the use of stable magnetic graphitic nanocapsules (MGNs), for in situ targeted magnetic resonance imaging (MRI) detection of H. pylori. Several layers of graphene as the shell effectively protect the magnetic core from corrosion while retaining the superior contrast effect for MRI in the gastric environment. Boronic-polyethylene glycol molecules were synthesized and modified on the MGN surface for targeted MRI detection. In a mouse model of H. pylori-induced infection, H. pylori was specifically detected through both T2-weighted MR imaging and Raman gastric mucosa imaging using functionalized MGNs. These results indicated that enhancement of MRI using MGNs may be a promising diagnostic and bioimaging platform for very harsh conditions.
Collapse
Affiliation(s)
- Yunjie Li
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Xiaoxiao Hu
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Ding Ding
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Yuxiu Zou
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Yiting Xu
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Xuewei Wang
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Yin Zhang
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Long Chen
- Faculty of Science and Technology, University of Macau, Av. da Universidade, Taipa 999078, Macau
| | - Zhuo Chen
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Weihong Tan
- Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China.,Department of Chemistry and Department of Physiology and Functional Genomics, Center for Research at Bio/nano Interface, Shands Cancer Center, UF Genetics Institute and McKnight Brain Institute, University of Florida, Gainesville, Florida 32611-7200, USA
| |
Collapse
|
|
10
|
Park JY, Dunbar KB, Mitui M, Arnold CA, Lam-Himlin DM, Valasek MA, Thung I, Okwara C, Coss E, Cryer B, Doern CD. Helicobacter pylori Clarithromycin Resistance and Treatment Failure Are Common in the USA. Dig Dis Sci 2016; 61:2373-2380. [PMID: 26923948 DOI: 10.1007/s10620-016-4091-8] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2016] [Accepted: 02/16/2016] [Indexed: 12/30/2022]
Abstract
BACKGROUND Helicobacter pylori antibiotic resistance leads to frequent treatment failure. However, the current US prevalence of H. pylori clarithromycin resistance and treatment failure is unknown. AIMS To determine the prevalence of clarithromycin-resistant H. pylori and its impact on treatment failure in the USA. METHODS A multicenter, retrospective, cohort study for clarithromycin-resistant H. pylori was conducted over four academic medical centers in different geographic regions of the USA. Gastric biopsy material, residual from standard clinical pathologic examination, was examined for clarithromycin resistance by DNA sequencing of H. pylori 23S rRNA. RESULTS One hundred and twenty-four cases of H. pylori gastritis were examined from medical centers in four different geographic regions of the USA. The overall prevalence of clarithromycin resistance was 32.3 % (range 23.1-45.8 %). There was no significant difference in the prevalence of clarithromycin resistance by study site, gender, age, or race/ethnicity. In a subset of 67 patients that had clinical follow-up data, the overall prevalence of clarithromycin resistance was 31.3 %. There was a 2.9-fold increase (p = 0.002) in treatment failure for cases with clarithromycin resistance (57.1 %) compared to wildtype H. pylori (19.6 %). CONCLUSIONS H. pylori clarithromycin resistance in the USA exceeds the estimated 20 % prevalence compatible with successful empiric antibiotic therapy. This resistance resulted in a significant rate of treatment failure in all sites surveyed. Empiric therapy in the USA should be used with caution until there is better regional or local determination of H. pylori antibiotic resistance.
Collapse
Affiliation(s)
- Jason Y Park
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
- Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, USA.
- Department of Pathology, Children's Health Dallas, 1935 Medical District Drive, Dallas, TX, 75235, USA.
| | - Kerry B Dunbar
- Medical Service, Dallas Veterans Affairs Medical Center, Dallas, TX, USA
- Division of Gastroenterology and Hepatology, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Midori Mitui
- Department of Pathology, Children's Health Dallas, 1935 Medical District Drive, Dallas, TX, 75235, USA
| | - Christina A Arnold
- Department of Pathology, Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Dora M Lam-Himlin
- Department of Pathology and Lab Medicine, Mayo Clinic, Arizona, Scottsdale, AZ, USA
| | - Mark A Valasek
- Division of Anatomic Pathology, Department of Pathology, University of California, San Diego, San Diego, CA, USA
| | - Irene Thung
- Division of Anatomic Pathology, Department of Pathology, University of California, San Diego, San Diego, CA, USA
| | - Chinemerem Okwara
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Elizabeth Coss
- Division of Gastroenterology and Hepatology, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Texas Digestive Disease Consultants, Dallas, TX, USA
| | - Byron Cryer
- Medical Service, Dallas Veterans Affairs Medical Center, Dallas, TX, USA
- Division of Gastroenterology and Hepatology, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Christopher D Doern
- Department of Pathology, Virginia Commonwealth University Health System, Richmond, VA, USA
| |
Collapse
|
|
11
|
Luo XF, Jiao JH, Zhang WY, Pu HM, Qu BJ, Yang BY, Hou M, Ji MJ. Establishment of a nested-ASP-PCR method to determine the clarithromycin resistance of Helicobacter pylori. World J Gastroenterol 2016; 22:5822-5830. [PMID: 27433095 PMCID: PMC4932217 DOI: 10.3748/wjg.v22.i25.5822] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2015] [Revised: 04/08/2016] [Accepted: 04/20/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate clarithromycin resistance positions 2142, 2143 and 2144 of the 23SrRNA gene in Helicobacter pylori (H. pylori) by nested-allele specific primer-polymerase chain reaction (nested-ASP-PCR).
METHODS: The gastric tissue and saliva samples from 99 patients with positive results of the rapid urease test (RUT) were collected. The nested-ASP-PCR method was carried out with the external primers and inner allele-specific primers corresponding to the reference strain and clinical strains. Thirty gastric tissue and saliva samples were tested to determine the sensitivity of nested-ASP-PCR and ASP-PCR methods. Then, clarithromycin resistance was detected for 99 clinical samples by using different methods, including nested-ASP-PCR, bacterial culture and disk diffusion.
RESULTS: The nested-ASP-PCR method was successfully established to test the resistance mutation points 2142, 2143 and 2144 of the 23SrRNA gene of H. pylori. Among 30 samples of gastric tissue and saliva, the H. pylori detection rate of nested-ASP-PCR was 90% and 83.33%, while the detection rate of ASP-PCR was just 63% and 56.67%. Especially in the saliva samples, nested-ASP-PCR showed much higher sensitivity in H. pylori detection and resistance mutation rates than ASP-PCR. In the 99 RUT-positive gastric tissue and saliva samples, the H. pylori-positive detection rate by nested-ASP-PCR was 87 (87.88%) and 67 (67.68%), in which there were 30 wild-type and 57 mutated strains in gastric tissue and 22 wild-type and 45 mutated strains in saliva. Genotype analysis showed that three-points mixed mutations were quite common, but different resistant strains were present in gastric mucosa and saliva. Compared to the high sensitivity shown by nested-ASP-PCR, the positive detection of bacterial culture with gastric tissue samples was 50 cases, in which only 26 drug-resistant strains were found through analyzing minimum inhibitory zone of clarithromycin.
CONCLUSION: The nested-ASP-PCR assay showed higher detection sensitivity than ASP-PCR and drug sensitivity testing, which could be performed to evaluate clarithromycin resistance of H. pylori.
Collapse
|
|
12
|
Loayza MF, Villavicencio FX, Santander SC, Baldeón M, Ponce LK, Salvador I, Vivar Díaz N. Improved method for extraction and detection of Helicobacter pylori DNA in formalin-fixed paraffin embedded gastric biopsies using laser micro-dissection. MethodsX 2014; 2:1-7. [PMID: 26150965 PMCID: PMC4487329 DOI: 10.1016/j.mex.2014.11.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2014] [Accepted: 11/26/2014] [Indexed: 01/24/2023] Open
Abstract
To assess the molecular events exerted by Helicobacter pylori interacting directly with gastric epithelial cells, an improved procedure for microbial DNA isolation from stained hematoxilin-eosin gastric biopsies was developed based on laser micro-dissection (LM) [1]. Few articles have described the use of LM to select and detect H. pylori genome from formalin-fixed paraffin embedded gastric tissue [2]. To improve the yield and quality of DNA isolated from H. pylori contacting intestinal epithelial cells, the following conditions were established after modification of the QIAamp DNA Micro kit.
Use of at least 25 cut sections of 10–20 μm of diameter and 3 μm thick with more than 10 bacteria in each cut. Lysis with 30 μL of tissue lysis buffer and 20 μL of proteinase K (PK) with the tube in an upside-down position. The use of thin purification columns with 35 μL of elution buffer. The mean of DNA concentration obtained from 25 LM cut sections was 1.94± 0 .16 ng/μL, and it was efficiently amplified with qPCR in a Bio Rad iCycler instrument. The LM can improve the sample selection and DNA extraction for molecular analysis of H. pylori associated with human gastric epithelium.
Collapse
Affiliation(s)
- María Fernanda Loayza
- Universidad de las Fuerzas Armadas ESPE, P.O. Box 171-5-231B, Av. General Rumiñahui s/n, Sangolquí, Ecuador ; Hospital Carlos Andrade Marín, P.O. Box 170411, Av. 18 de Septiembre s/n y Ayacucho, Quito, Ecuador
| | | | | | - Manuel Baldeón
- Centro de Investigación Traslacional, Universidad de las Américas, Calle José Queri. Quito, Ecuador
| | - Lourdes Karina Ponce
- Universidad de las Fuerzas Armadas ESPE, P.O. Box 171-5-231B, Av. General Rumiñahui s/n, Sangolquí, Ecuador
| | - Iván Salvador
- Hospital Carlos Andrade Marín, P.O. Box 170411, Av. 18 de Septiembre s/n y Ayacucho, Quito, Ecuador
| | - Nicolás Vivar Díaz
- Hospital Carlos Andrade Marín, P.O. Box 170411, Av. 18 de Septiembre s/n y Ayacucho, Quito, Ecuador ; NETLAB S.A., Calle "A" (Oe7A) N31-145 y Av. Mariana de Jesús, Quito, Ecuador
| |
Collapse
|
|
13
|
Gulley ML, Morgan DR. Molecular oncology testing in resource-limited settings. J Mol Diagn 2014; 16:601-11. [PMID: 25242061 PMCID: PMC4210462 DOI: 10.1016/j.jmoldx.2014.07.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2014] [Revised: 07/15/2014] [Accepted: 07/22/2014] [Indexed: 12/14/2022] Open
Abstract
Cancer prevalence and mortality are high in developing nations, where resources for cancer control are inadequate. Nearly one-quarter of cancers in resource-limited nations are infection related, and molecular assays can capitalize on this relationship by detecting pertinent pathogen genomes and human gene variants to identify those at highest risk for progression to cancer, to classify lesions, to predict effective therapy, and to monitor tumor burden over time. Prime examples are human papillomavirus in cervical neoplasia, Helicobacter pylori and Epstein-Barr virus in gastric adenocarcinoma and lymphoma, and hepatitis B or C virus in hepatocellular cancer. Research is underway to engineer devices that overcome social, economic, and technical barriers limiting effective laboratory support. Additional challenges include an educated workforce, infrastructure for quality metrics and record keeping, and funds to sustain molecular test services. The combination of well-designed interfaces, novel and robust electrochemical technology, and telemedicine tools will promote adoption by frontline providers. Fast turnaround is crucial for surmounting loss to follow-up, although increased use of cell phones, even in rural areas, enhances options for patient education and engagement. Links to a broadband network facilitate consultation and centralized storage of medical data. Molecular technology shows promise to address gaps in health care through rapid, user-friendly, and cost-effective devices reflecting clinical priorities in resource-poor areas.
Collapse
Affiliation(s)
- Margaret L Gulley
- Department of Pathology and Laboratory Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina.
| | - Douglas R Morgan
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University, Nashville, Tennessee
| |
Collapse
|
|
14
|
Abstract
The present manuscript focuses on the new information that was published in the field of diagnosis of Helicobacter pylori this past year. While there is little news about the invasive tests, more data are coming concerning the endoscopic features of H. pylori infection. Major efforts were also done to improve molecular detection of the mutations involved in antibiotic resistance. New antibody-based tests (stool antigen test or indirect antibody tests) were also developed.
Collapse
Affiliation(s)
- Francis Mégraud
- Laboratoire de bactériologie, Université de Bordeaux, 33076, Bordeaux, France; INSERM U853, 33076, Bordeaux, France
| | | | | |
Collapse
|
|
15
|
Lopes AI, Vale FF, Oleastro M. Helicobacter pylori infection - recent developments in diagnosis. World J Gastroenterol 2014; 20:9299-9313. [PMID: 25071324 PMCID: PMC4110561 DOI: 10.3748/wjg.v20.i28.9299] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2013] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
Considering the recommended indications for Helicobacter pylori (H. pylori) eradication therapy and the broad spectrum of available diagnostic methods, a reliable diagnosis is mandatory both before and after eradication therapy. Only highly accurate tests should be used in clinical practice, and the sensitivity and specificity of an adequate test should exceed 90%. The choice of tests should take into account clinical circumstances, the likelihood ratio of positive and negative tests, the cost-effectiveness of the testing strategy and the availability of the tests. This review concerns some of the most recent developments in diagnostic methods of H. pylori infection, namely the contribution of novel endoscopic evaluation methodologies for the diagnosis of H. pylori infection, such as magnifying endoscopy techniques and chromoendoscopy. In addition, the diagnostic contribution of histology and the urea breath test was explored recently in specific clinical settings and patient groups. Recent studies recommend enhancing the number of biopsy fragments for the rapid urease test. Bacterial culture from the gastric biopsy is the gold standard technique, and is recommended for antibiotic susceptibility test. Serology is used for initial screening and the stool antigen test is particularly used when the urea breath test is not available, while molecular methods have gained attention mostly for detecting antibiotic resistance.
Collapse
|
|
16
|
De Francesco V, Zullo A, Giorgio F, Saracino I, Zaccaro C, Hassan C, Ierardi E, Di Leo A, Fiorini G, Castelli V, Lo Re G, Vaira D. Change of point mutations in Helicobacter pylori rRNA associated with clarithromycin resistance in Italy. J Med Microbiol 2014; 63:453-457. [PMID: 24344205 DOI: 10.1099/jmm.0.067942-0] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Primary clarithromycin resistance is the main factor affecting the efficacy of Helicobacter pylori therapy. This study aimed: (i) to assess the concordance between phenotypic (culture) and genotypic (real-time PCR) tests in resistant strains; (ii) to search, in the case of disagreement between the methods, for point mutations other than those reported as the most frequent in Europe; and (iii) to compare the MICs associated with the single point mutations. In order to perform real-time PCR, we retrieved biopsies from patients in whom H. pylori infection was successful diagnosed by bacterial culture and clarithromycin resistance was assessed using the Etest. Only patients who had never been previously treated, and with H. pylori strains that were either resistant exclusively to clarithromycin or without any resistance, were included. Biopsies from 82 infected patients were analysed, including 42 strains that were clarithromycin resistant and 40 that were clarithromycin susceptible on culture. On genotypic analysis, at least one of the three most frequently reported point mutations (A2142C, A2142G and A2143G) was detected in only 23 cases (54.8%), with a concordance between the two methods of 0.67. Novel point mutations (A2115G, G2141A and A2144T) were detected in a further 14 out of 19 discordant cases, increasing the resistance detection rate of PCR to 88% (P<0.001; odds ratio 6.1, 95% confidence interval 2-18.6) and the concordance to 0.81. No significant differences in MIC values among different point mutations were observed. This study suggests that: (i) the prevalence of the usually reported point mutations may be decreasing, with a concomitant emergence of new mutations; (ii) PCR-based methods should search for at least six point mutations to achieve good accuracy in detecting clarithromycin resistance; and (iii) none of the tested point mutations is associated with significantly higher MIC values than the others.
Collapse
Affiliation(s)
| | - Angelo Zullo
- Gastroenterology and Digestive Endoscopy, 'Nuovo Regina Margherita' Hospital, Rome, Italy
| | - Floriana Giorgio
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - Ilaria Saracino
- Department of Clinical Medicine, University of Bologna, Bologna, Italy
| | - Cristina Zaccaro
- Department of Clinical Medicine, University of Bologna, Bologna, Italy
| | - Cesare Hassan
- Gastroenterology and Digestive Endoscopy, 'Nuovo Regina Margherita' Hospital, Rome, Italy
| | - Enzo Ierardi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - Alfredo Di Leo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - Giulia Fiorini
- Department of Clinical Medicine, University of Bologna, Bologna, Italy
| | | | - Giovanna Lo Re
- Department of Clinical Medicine, University of Bologna, Bologna, Italy
| | - Dino Vaira
- Department of Clinical Medicine, University of Bologna, Bologna, Italy
| |
Collapse
|
|
17
|
Ierardi E, Giorgio F, Losurdo G, Di Leo A, Principi M. How antibiotic resistances could change Helicobacter pylori treatment: A matter of geography? World J Gastroenterol 2013; 19:8168-8180. [PMID: 24363506 PMCID: PMC3857438 DOI: 10.3748/wjg.v19.i45.8168] [Citation(s) in RCA: 80] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2013] [Revised: 10/18/2013] [Accepted: 11/03/2013] [Indexed: 02/06/2023] Open
Abstract
Therapeutic management of Helicobacter pylori (H. pylori) remains an unsolved issue. Indeed, no therapeutic regimen is able to cure the infection in all treated patients, and in many the infection persists despite the administration of several consecutive standard therapies. Although antibiotic resistance reports describe alarming results, the outcome of therapeutic regimens does not seem to parallel this scenario in most cases, since a successful performance is often reached in more than 80% of cases. However, the phenomenon of increasing antibiotic resistance is being closely studied, and the results show controversial aspects even in the same geographic area. For the continents of Europe, America, Asia, Africa, and Oceania, minimal and maximal values of resistance to the main antibiotics (clarithromycin, amoxicillin, metronidazole, and levofloxacin) feature wide ranges in different countries. The real enigma is therefore linked to the several different therapeutic regimens, which show results that often do not parallel the in vitro findings even in the same areas. A first aspect to be emphasized is that some regimens are limited by their use in very small geographic districts. Moreover, not all therapeutic trials have considered bacterial and host factors affecting the therapeutic outcome. The additional use of probiotics may help to reduce adverse events, but their therapeutic impact is doubtful. In conclusion, the "ideal therapy", paradoxically, appears to be a "utopia", despite the unprecedented volume of studies in the field and the real breakthrough in medical practice made by the discovery and treatment of H. pylori. The ample discrepancies observed in the different areas do not encourage the development of therapeutic guidelines that could be valid worldwide. On these bases, one of the main challenges for the future might be identifying a successful solution to overcome antibiotic resistances. In this context, geography must be considered a relevant matter.
Collapse
|
|
18
|
Abstract
PURPOSE OF REVIEW This review focuses on new aspects of recently published guidelines for the management of Helicobacter pylori infection as well as progress in diagnostic tests and treatment regimens. We also discuss new strategies for gastric cancer prevention. RECENT FINDINGS The general recommendation to treat H. pylori infection whenever diagnosed still faces resistance for reasons that are pertinent to the diversity of related clinical outcomes and to the complexity of eradication regimens. Thus, new updated guidelines for the management of H. pylori infection have been released in several continents. Progress has been made in molecular diagnostic tests for the detection of antibiotic resistance and serological tests for the detection of advanced gastric atrophic changes. Effective quadruple therapies in various combinations of 'traditional drugs' have been introduced with sequential or concomitant order of administration. Moreover, traditional drugs in a new galenic formulation have been introduced to overcome increasing H. pylori antibiotic resistance. Effective strategies for gastric cancer prevention have been adopted in some countries with high gastric cancer incidence, and have successfully contributed to lower the gastric cancer incidence. A screen-and-treat strategy for individuals at increased risk for gastric cancer needs to be further explored also in areas with low/moderate incidence of gastric cancer. SUMMARY New guidelines share many universal similarities across countries but respect and emphasize specific needs and requirements in individual communities. Various combinations of traditional drugs have been successfully introduced to overcome the increasing H. pylori antibiotic resistance. Gastric cancer prevention by a screen and treat strategy showed promising results.
Collapse
|