Molecular genetic predictors of Helicobacter pylori resistance to eradication regimens in the Republic of Kazakhstan

AP19575049

Objective: To determine the regional genotypes and the level of resistance to H. pylori antibacterial drugs, as well as the value and effectiveness of molecular genetic methods in the diagnosis and evaluation of eradication therapy of diseases associated with H. pylori in Kazakhstan.

Relevance

In contemporary clinical practice, there i no optimal empirical therapy for H. pylori infection and there is a progressive decrease in the effectiveness of classical eradication therapy regimens. The new version of the MAASTRICHT VI consensus of 08.08.2022 introduced a provision on molecular diagnostic methods (in particular, real-time PCR, genome-wide sequencing and digital PCR) to detect H. pylori mutations associated with resistance to clarithromycin, levofloxacin, tetracycline and rifampicin considering the increasing antibiotic resistance. Furthermore, before administering any therapy regimens containing clarithromycin, it is recommended to conduct a clarithromycin sensitivity test using molecular or bacteriological methods, if available. For molecular testing using PCR, it is proposed to use stomach biopsies extracted from rapid urease tests (rapid urease test). Genotypic and phenotypic markers of H. pylori are recommended to be used for personalized eradication therapy.

Detection of H. pylori, determination of sensitivity to antimicrobial drugs by classical microbiological methods is a complex process that requires certain competencies and it is not always a guarantor of the detection of the pathogen. As a result, more and more laboratories are focusing on molecular genetic methods in the diagnosis of H. pylori. After all, they allow you to analyze the structure of the pathogen, its genome, mutations, virulence genes, antimicrobial resistance genes.

In addition, research concerning the search for phylogenetic lines is becoming increasingly popular. The resulting H. pylori may have phylogeographic differentiation. The genotypes of the studied H. pylori can potentially be used as markers of migration of human populations.

Asymptomatic carriers of H. pylori may be at risk for the development of chronic processes in the gastrointestinal tract, up to cancerous conditions. Knowing the genetic variability of the pathogen, it is possible to predict the course of the disease.

Expected results

Based on the results of this study, it is planned to identify the circulation of resistant strains and the dynamics of their spread, to identify groups with certain genotypes resistant to standard schemes of anti-helicobacter therapy. It is planned to obtain the first data in Kazakhstan on the population genetics of H. pylori.

For the first time we will try to determine the regional features of genotypes H. pylori in Kazakhstan. Data will be obtained on the effectiveness or inefficiency of the classical cultural and molecular genetic method in the diagnosis of H. pylori. Data on the identification of H. pylori on MALDI-TOF with the creation of its own local libraries will be obtained.

Data on molecular genetic predictors of H. pylori resistance to eradication therapy regimens in the Republic of Kazakhstan will be obtained.

The concept of the fundamentals of population genetics of H. pylori will allow for a deeper study of the origin of the strain, providing a new way to understand the information and mechanisms of antibiotic resistance. All this will help to develop up-to-date diagnostic approaches for predicting pathogenic and non-pathogenic strains in the development of gastric ulcer, duodenal ulcer or adenocarcinoma. This project has a potential socio-economic effect, which consists in choosing the optimal method for diagnosing H. pylori, determining sensitivity to antimicrobial drugs in Kazakhstan, as well as determining regional genotypes and levels of resistance to antibacterial drugs when planning therapeutic strategies for H. pylori infection.

H.pylori, определения чувствительности к антимикробным препаратам на территории Казахстана, а также, определения региональных генотипов и уровней резистентности к антибактериальным препаратам при планировании терапевтических стратегий инфекции H.рylori.

The obtained data on the population genetics of H. pylori in Kazakhstan will make it possible to make changes to the diagnostic algorithm with the further prospect of finalizing the treatment concept according to the global trends of personalized medicine. The relevance of the obtained results will be applied both for applied clinical tasks and in the field of fundamental medicine. The areas of application of the research results and target consumers include: pharmacology, oncology, immunology, clinical microbiology, laboratory diagnostics, therapy, gastroenterology.

Based on these results, it is planned to publish at least 2 (two) at least 2 (two) articles and (or) reviews in peer-reviewed scientific publications in the scientific direction of the project, indexed in the Science Citation Index Expanded of the Web of Science database and (or) having a CiteScore percentile in the Scopus database of at least 35 (thirty-five), at least 1 (one) article or review in a peer-reviewed foreign or domestic publication, recommended by CQAFSHE.

    Research Group

Full name, Education, degree academic title

Main place of work, position

The hirsch index, ResearcherID identifiers, ORCHID, Scopus Author ID

Role in the project or program and nature of the work performed

List of publications

1

Ekaterina Alexandrovna Yukhnevich, PhD, Associate Professor

NАО "KMU", associate professor

The hirsch index– 2 Web of Science Researcher ID AAT-1398-2020 ORCID ID 0000-0001-5992-0336– 2 Web of Science Researcher ID AAT-1398-2020 ORCID ID 0000-0001-5992-0336

Scientific director

Project manager, coordinator. General project management, coordination of group activities, task monitoring, data analysis, publication writing.

1. G. Kemelova; I. Shekhter; D.Aimbetova; V.Riklefs; Y. Yukhnevich. Digitalization of the clinical exam in Covid-19 pandemic: Karaganda Medical University’s experience//Journal of Clinical Medicine of Kazakhstan

2022-04-30 | Journal article

DOI: 10.23950/jcmk/11942

2. D.Yesniyazov; Tussupbekova M.; N.Abatov; Y. Yukhnevich; 

R.Badyrov Myringoplasty with Morphological Rationale of Application of Xenoperitoneum Decellularized Matrix in Experiment// Open Access Macedonian Journal of Medical Sciences

2021-10-05 | Journal article

DOI: 10.3889/oamjms.2021.5897

3. D.Kaliyeva; Y.Yukhnevich; 

N.Abatov; A. Nurbekov., Difficulties in diagnosing the alveolar echinococcosis (case report)., International Journal of Surgery Case Reports

2020 | Journal article

DOI: 10.1016/j.ijscr.2020.08.025

S Kaliyeva; N Simohina; Y Yukhnevich; Z Myasnikova; Y Myasnikov; Yekaterina Yukhnevich., Pharmacoeconomic Assessment of Biological Therapy of Ulcerative Colitis, Value in Health

2018-05 | Conference abstract | Writing - original draft, Methodology

DOI: 10.1016/j.jval.2018.04.567

Begaidarova,R.; Kaliyeva, S.; Yukhnevich, Y.; Tonkabaeva, B.; Begey, N., SAUSALIN VS METRONIDAZOLE IN TREATMENT OF GIARDIASIS: PHARMACOECONOMIC ASSESSMENT, Value in Health

2017 | Journal article

WOSUID: WOS:000405448001075

Begaydarova,R.; Yukhnevich, Y.; Babenko, D.; Kaliyeva, S.; Azizov, I.; Muldaeva, G.; Omarkulov, B., Determination of PFOR gene expression in strains of G. intestinalis with different inhibitory concentrations of metronidazole., Journal of Infection in Developing Countries

2015 | Journal article

DOI: 10.3855/jidc.5768

Begaydarova,R.H.; Kultanov, B. Z.; Esilbaeva, B.T.; Nasakaeva,G.E.; Yukhnevich,Y.A.; Alshynbekova, G. K.; Dyusembaeva, A. E., The investigation of endogenous intoxication and lipid peroxidation in patients with giardiasis before and after treatment, The FEBS Journal

2015 | Journal article

WOSUID: WOS:000362570602099

S Kalyieva; N Minakova; Y Yukhnevich-Nassonova., Cost-Effectiveness Analysis of the Original Drug Arglabin., Value in Health

2014-11 | Journal article

DOI: 10.1016/j.jval.2014.08.103

Begaydorova RKh; Nasakaeva GE; Tabagari SI; Alshinbekova GK; Yekaterina Yukhnevich., Clinical and diagnostic features and treatment of giardiasis, Georgian medical news

2014-11-01 | Journal article

PMID: 25541827

Yekaterina Yukhnevich; Begaydarova, R; Kultanov,B.Zh; Yukhnevich-Nassonova, Y.; Kuzgibekova, A; Nasakaeva, G,. Evaluation of cytogenetic changes in somatic cells in patients with giardiasis (Definition of micronucleus test in somatic cells - cells with buccal mucosa), Global Journal on Advances in Pure & Applied Sciences

2014-04 | Journal article

2

Lavrinenko Alyona Vladimirovna

NАО KMU, Associate Professor, Head of the laboratory

The hirsch index– 3 R ID - 20,56 ORCID 0000-0001-9436-8778. Scopus Author ID 57193763117

Responsible executor. Coordinator, collection of material, microbiological part of the work, writing publications

1. Bacterial Co-Infections and Antimicrobial Resistance in Patients Hospitalized with Suspected or Confirmed COVID-19 Pneumonia in Kazakhstan. Lavrinenko, A., Kolesnichenko, S., Kadyrova, I., Akhmaltdinova, L. Klyuyev, D. Pathogens, 2023, 12(3), 370.                                                                2. The Presence of PDL-1 on CD8+ Lymphocytes Is Linked to Survival in Neonatal Sepsis. Akhmaltdinova, L.L., Zhumadilova, Z.A., Kolesnichenko, S.I., Panibratec, L.G., Vinogradskaya, E.V.. Children, 2022, 9(8), 1171.                                                                                                                                           3. Bacterial Colonization Incidence before and after Indwelling Double-J Ureteral Stents. Kaliyeva, S., Simokhina, N., Lavrinenko, A., Yelmagambetov, B., Myasnikova, Z.. Antibiotics, 2022, 11(7), 850.                                                                                                           4. ANTIBIOTIC RESISTANCE AND GENOTYPES OF NOSOCOMIAL STRAINS OF ACINETOBACTER BAUMANNII IN KAZAKHSTAN. Lavrinenko A., Kolesnichenko S., Turmukhambetova A., Sheck E., Azizov I. Antibiotics. 2021. Т. 10. № 4.                                                                                                           5. Mortality Risk Factors of Early Neonatal Sepsis During COVID-19 Pandemic. Kolesnichenko, S.I., Kadyrova, I.A., Lavrinenko, A.V., Panibratec, L.G., Akhmaltdinova, L.L. Infection and Drug Resistancethis link is disabled, 2022, 15, страницы 6307–6316 Antibiotics, 2021, 10(4), 382.                                             6.BLOODSTREAM INFECTION ETIOLOGY AMONG CHILDREN AND ADULTS. Kolesnichenko S.I.,. Lavrinenko A.V., Akhmaltdinova L.L. International Journal of Microbiology. 2021. Т. 2021. С. 6657134.                                                                                                               7. INFLUENCE OF PATHOGEN TYPE ON NEONATAL SEPSIS BIOMARKERS. Akhmaltdinova L., Kolesnichenko S., Lavrinenko A., Kadyrova I., Avdienko O., Panibratec L. International Journal of Inflammation. 2021. Т. 2021. С. 1009231.                                                                                          8.STUDY OF THE PHENOLIC COMPOUNDS OF THE DRY EXTRACT OF THYMUS CREBRIFOLIUS USING A COMBINED HPLC-UV AND HPLC-ESI-MS/MS METHOD. Ivasenko S.A., Shakarimova K.K., Bokayeva A.B., Marchenko A.B., Lavrinenko A.V., Kolesnichenko S.I. Bulletin of the Karaganda University. Chemistry Series. 2021. № 2 (102). С. 18-23.                                                                                                    9.СОСТОЯНИЕ АНТИБИОТИКОРЕЗИСТЕНТНОСТИ ВОЗБУДИТЕЛЕЙ ВНЕБОЛЬНИЧНЫХ ИНФЕКЦИЙ МОЧЕВЫВОДЯЩИХ ПУТЕЙ В РОССИИ, БЕЛАРУСИ И КАЗАХСТАНЕ: РЕЗУЛЬТАТЫ МНОГОЦЕНТРОВОГО МЕЖДУНАРОДНОГО ИССЛЕДОВАНИЯ «ДАРМИС-2018» Палагин И.С., Сухорукова М.В., Дехнич А.В., Эйдельштейн М.В., Перепанова Т.С., Козлов Р.С., Мутин М.Ю., Стребкова В.В., Тапальский Д.В., Аминева П.Г., Ветохина А.В., Сухорева М.В., Иванова И.А., Валиуллина И.Р., Лавриненко А.В., Частоедова А.Н., Широкова Т.М., Варибрус Е.В., Васильева И.Р., Доманская О.В. и др. Урология. 2020. № 1. С. 19-31.                                                                                                 10.ПНЕВМОНИИ, АССОЦИИРОВАННЫЕ С SARS-COV-2. Лавриненко А.В., Колесниченко С.И., Турмухамбетова А.А., Кадырова И.А. Вестник Казахского национального медицинского университета. 2020. № 4. С. 301-307.                                                                                      11.СПЕКТР И ЛЕКАРСТВЕННАЯ ЧУВСТВИТЕЛЬНОСТЬ НЕСПЕЦИФИЧЕСКОЙ ФЛОРЫ У БОЛЬНЫХ ТУБЕРКУЛЕЗОМ С МНОЖЕСТВЕННОЙ ЛЕКАРСТВЕННОЙ УСТОЙЧИВОСТЬЮ Лавриненко А.В., Азизов И.С., Колесниченко С.И., Кожамуратов М.Т., Табриз Н.С., Мутайхан Ж.
Туберкулез и болезни легких. 2019. Т. 97. № 9. С. 11-16.

3

Kadyrova Irina Adilyevna, PhD

NАО "KMU", senior resercher

The hirsch index – 4 ORCID 0000-0001-7173-3138 Scopus 56297966100 Publons V-8868-2019

Performer

molecular genetic research, statistical analysis, analysis of data obtained, writing publications

1. Biomarkers of immunothrombosis and polymorphisms of IL2, IL6, and IL10 genes as predictors of the severity of COVID-19 in a Kazakh population/ Yessenbayeva, A., Apsalikov, B. Massabayeva, M., Aukenov, N..// PLoS ONEthis link is disabled, 2023, 18(6 JUNE), e0288139.                                                      2. Bacterial Co-Infections and Antimicrobial Resistance in Patients Hospitalized with Suspected or Confirmed COVID-19 Pneumonia in Kazakhstan. Lavrinenko, A., Kolesnichenko, S. Kadyrova, I., Akhmaltdinova, L., Klyuyev, D. Pathogens, 2023, 12(3), 370                                                        3.Genetic Predictors of the Development of Complications after Coronary Stenting.Taizhanova, D., Kalimbetova, A., Bodaubay, R., Akilzhanova, A., Gerotziafas, G.T. Journal of Personalized Medicine, 2023, 13(1), 14.                                                                                                                                     4. Sputnik-V reactogenicity and immunogenicity in the blood and mucosa: a prospective cohort study
Yegorov, S., Kadyrova, I., Negmetzhanov, B., Hortelano, G.H., Babenko, D. Scientific Reportsthis link is disabled, 2022, 12(1), 13207.                                                                                                          5. Sustained Delivery of a Monoclonal Antibody against SARS-CoV-2 by Microencapsulated Cells: A Proof-of-Concept Study. Ashimova, A., Myngbay, A. , Yegorov, S. Miller, M.S., Hortelano, G. Pharmaceuticsthis link is disabled, 2022, 14(10), 2042                                                                                                  6. The Presence of PDL-1 on CD8+ Lymphocytes Is Linked to Survival in Neonatal Sepsis. Akhmaltdinova, L.L., Zhumadilova, Z.A., Kolesnichenko, S.I., Panibratec, L.G., Vinogradskaya, E.V. Children, 2022, 9(8), 1171.                                                                                                                                           7. High SARS-CoV-2 seroprevalence in Karaganda, Kazakhstan before the launch of COVID-19 vaccination
Kadyrova, I., Yegorov, S., Negmetzhanov, B., Hortelano, G., Babenko, D. PLoS ONEthis link is disabled, 2022, 17(7 July), e0272008.                                                                                                             8. Mortality Risk Factors of Early Neonatal Sepsis During COVID-19 Pandemic. Kolesnichenko, S.I., Kadyrova, I.A., Lavrinenko, A.V., Panibratec, L.G., Akhmaltdinova, L.L. Infection and Drug Resistancethis link is disabled, 2022, 15, 6307–6316.                                                                                              9. ssociation of four genetic variants with colorectal cancer in kazakhstan population
Kolesnikova, Y., Babenko, D, Kadyrova, I., Vazenmiller, D., Turmukhambetova, A. Oncotargetthis link is disabled, 2021, 12(21), 2215–2222.                                                                                                10. General characteristics for loading the working elements of drilling and milling machines when moving in the clay solution. Kadyrov, A., Zhunusbekova, Z. , Ganyukov, A., Kadyrova, I., Kukesheva, A. Communications - Scientific Letters of the University of Žilinathis link is disabled, 2021, 23(2), B97–B105.

4

Solomadin Maxim Valeryevich, Master

NАО "KMU", 3rd year doctoral student

ORCID ID 0000-0002-1400-3267

Performer

Molecular genetic research, analysis of laboratory data.

G.Kairova; N.Daulet; M. Solomadin; N. Sandybayev; S. Orkara; V. Beloussov; N.Kerimbek; D.Gritsenko; Z.Sapakhova,.Identification of Apple Varieties Resistant to Fire Blight (Erwinia amylovora) Using Molecular Markers., Horticulturae

2023-09-04 | Journal article

DOI: 10.3390/horticulturae9091000

B.S. Ilyassova; B.Abzhaparova; D. S. Smailova; A.Bolatov; B.Baymakhanov; V.Beloussov; M.Solomadin; K. Shamsivaliyeva; G.Alpysbayava; G. Issakova et al., Prevalence and genotypes distribution of virus hepatitis B and hepatitis delta virus in chronic liver diseases in Kazakhstan., BMC Infectious Diseases

2023-08-14 | Journal article

DOI: 10.1186/s12879-023-08524-1

N.Sandybayev; V.Beloussov; V. Strochkov; M.Solomadin; J. Granica; S. Yegorov., Characterization of viral pathogens associated with symptomatic upper respiratory tract infection in adults during a low COVID-19 transmission period., PeerJ

2023-03-13 | Journal article

DOI: 10.7717/peerj.15008

N.Sandybayev; V. Beloussov; Vitaliy Strochkov; M.Solomadin; J.Granica; S.Yegorov., Next Generation Sequencing Approaches to Characterize the Respiratory Tract Virome., Microorganisms

2022-11-24 | Journal article

DOI: 10.3390/microorganisms10122327

Lavrinenko, A. V.; Azizov, I.; Solomadin, M.; Kolesnichenko, S.., Molecular-genetic features of MSSA, isolated in Kazakhstan., International Journal of Infectious Diseases

2018 | Journal article

DOI: 10.1016/J.IJID.2018.04.3773

Kalimagambetov, A.; Isabek, A.; Valyayeva, M.; Rakisheva, Z.; Beisembaeva, S.; Sadueva, K.; Solomadin, M., Polymorphism of thrombophilia genes of the blood coagulation system in women of the Kazakh ethnic group with a habitual miscarriage., The FEBS Journal

2017 | Journal article

WOSUID: WOS:000409918902086

The FEBS Journal

2017 | Journal article

WOSUID: WOS:000409918902086., THE TRANSMISSIVE ROUTE OF BACILLUS ANTHRACIS INFECTION., The American Journal of Tropical Medicine and Hygiene

2010 | Journal article

WOSUID: WOS:000295819700194

5

Alexey Pavlovich Shkreba

NАО "KMU", endoscopist

Performer

Performing endoscopy, collecting material

6

Simokhina Natalia Andreevna

NАО "KMU", assistant professor

Performer

Clinical part of the work, monitoring the effectiveness of eradication regimens, statistical analysis, writing publications

7

Ryazanets Darya Anatolyevna

8

Turemuratova Aidana Bauyrzhanovna

NАО "KMU", trainee research

ORCID 0000-0003-2322-304X

Исполнитель

Участие в постановке культурального метода, определение чувствительности к антибиотикам

1.Лавриненко А.В., Туремуратова А.Б., Пралиева А.Б. Определение чувствительности к колистину методом микроразведений в бульоне с использованием стандартных дисков -// журнал Клиническая Микробиология и Антимикробная Химиотерапия. – Том 24, 2022 . С 23. ISSN 1684-4386


The process of cultivation, identification and preservation of samples has begun. Also, a stage of work has begun to determine the sensitivity of H. pylori to antimicrobial drugs.

Information for potential users.

The results of the study will be useful in the diagnosis of H. pylori in gastroenterology.