Epidemiology of Helicobacter pylori and CagA-Positive Infections and Global Variations in Gastric Cancer

Gastric cancer is a major health burden and is the fifth most common malignancy and the third most common cause of death from cancer worldwide. Development of gastric cancer involves several aspects, including host genetics, environmental factors, and Helicobacter pylori infection. There is increasing evidence from epidemiological studies of the association of H. pylori infection and specific virulence factors with gastric cancer. Studies in animal models indicate H. pylori is a primary factor in the development of gastric cancer. One major virulence factor in H. pylori is the cytotoxin-associated gene A (cagA), which encodes the CagA protein in the cag pathogenicity island (cag PAI). Meta-analysis of studies investigating CagA seropositivity irrespective of H. pylori status identified that CagA seropositivity increases the risk of gastric cancer (OR = 2.87, 95% CI: 1.95–4.22) relative to the risk of H. pylori infection alone (OR = 2.31, 95% CI: 1.58–3.39). Eradicating H. pylori is a strategy for reducing gastric cancer incidence. A meta-analysis of six randomised controlled trials (RCTs) suggests that searching for and eradicating H. pylori infection reduces the subsequent incidence of gastric cancer with a pooled relative risk of 0.66 (95% CI: 0.46–0.95). The introduction in regions of high gastric cancer incidence of population-based H. pylori screening and treatment programmes, with a scientifically valid assessment of programme processes, feasibility, effectiveness and possible adverse consequences, would impact the incidence of H. pylori-induced gastric cancer. Given the recent molecular understanding of the oncogenic role of CagA, targeting H. pylori screening and treatment programmes in populations with a high prevalence of H. pylori CagA-positive strains, particularly the more oncogenic East Asian H. pylori CagA strains, may be worth further investigation to optimise the benefits of such strategies

The Effectiveness Test Of Wound Healing Daun Gatal (Laportea Decumana) Against Mice (Mus Musculus L)

Daun Gatal (Laportea spp) is one of the shrubs that are widely distributed in Papua from the coast to the mountains. Daun Gatal (Laportea spp) has been used for generations by the Papuan people as painkillers. Daun Gatal (Laportea spp) contains compounds monoxide, tryptophan, histidine, alkaloids, flavonoids, formic acid, and anthraquinones. This content is called "antacid" because it gives a sensation like being bitten by an ant. There are many itchy leaves in the village but often they are just left to dry, wither, die, and even be thrown away. The value of this leaf is very large if it is developed not only as an itchy leaf sheet but as a pharmaceutical product. (Simaremare, et al, 2019). This is supported by several research results stating that itchy leaf extract contains compounds of the alkaloid group, glycosides, steroids (Simaremare, 2014), also contains triterpenoid compounds and formic acid (Chrystomo, et al., 2016) and (Krisna and Santanina, 2019) which states that itchy leaves provide antibacterial activity. The type of research used is experimental research. The research design used was a randomized control group pretest and posttest design. The population in this study was white mice. The samples used in this study were white mice that had met the following inclusion and exclusion criteria. Inclusion criteria were female mice, bodyweight 20-30grams, age 2-4 months while the exclusion criteria. Included in the exclusion criteria in this study were mice that were sick or died in the study conditions. The results of the Extraction of Daun Gatal (Laportea Decumana), namely the itchy leaf sample that has been weighed at a concentration of 25% obtained from a mixture of itching leaf extract (25 grams) added with water (30 ml) produces 18.5 ml. Itchy leaf extract at a concentration of 50 % was obtained from a mixture of itchy leaf extract (50 grams) added with water (30 ml) to produce 20.1 ml. Gatak leaf extract at a concentration of 75% was obtained from a mixture of itching leaf extract (75 grams) added with water (30 ml) to produce 24.3 ml. The extraction method used is extracting the extract of itchy leaves. This method was chosen because the process is simple and does not involve heating so that it can prevent damage to chemical compounds that are not resistant to heating, especially flavonoids contained in itchy leaves. Based on the results of the data on the difference in wound diameter of mice, it showed that Treatment Group 1 with 25% itching leaf extract and Treatment Group 2 with 50% itching leaf extract almost had the same healing rate. Meanwhile, Treatment Group 3 with 75% itching leaf extract had the fastest healing rate among other concentrations. In contrast to Treatment Group 3, the control group had a much longer healing rate among other concentrations

Alternative eradication regimens for Helicobacter pylori infection in Indonesian regions with high metronidazole and levofloxacin resistance

Muhammad Miftahussurur,1,2 Langgeng Agung Waskito,2,3 Ari Fahrial Syam,4 Iswan Abbas Nusi,1 Gontar Siregar,5 Marselino Richardo,6 Achmad Fuad Bakry,7 Yudith Annisa Ayu Rezkitha,2,8 I Dewa Nyoman Wibawa,9 Yoshio Yamaoka3,10,11 1Division of Gastroentero-hepatology, Department of Internal Medicine, Faculty of Medicine, Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya 60131, Indonesia; 2Institute of Tropical Disease, Universitas Airlangga, Surabaya 60115, Indonesia; 3Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu 879-5593, Japan; 4Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta 10430, Indonesia; 5Division of Gastroentero-hepatology, Department of Internal Medicine, Faculty of Medicine, University of Sumatera Utara, Medan 20136, Indonesia; 6Department of Internal Medicine, Merauke City General Hospital, Merauke 99656, Indonesia; 7Division of Gastroentero-hepatology, Department of Internal Medicine, Faculty of Medicine, Sriwijaya University, Palembang 30126, Indonesia; 8Department of Internal Medicine, Muhammadiyah University of Surabaya, Surabaya 60113, Indonesia; 9Division of Gastroentero-hepatology, Department of Internal Medicine, Faculty of Medicine, University of Udayana, Denpasar 80232, Indonesia; 10Department of Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX 77030, USA; 11Global Oita Medical Advanced Research Center for Health, Yufu 879-5593, Japan Background: The prevalence of Helicobacter pylori resistance to metronidazole and clarithromycin is high in Indonesia. Moreover, the increasing levofloxacin resistance rates in the absence of bismuth treatment in Indonesia has led to the use of other antibiotics as alternative regimens. Methods: We determined the minimum inhibitory concentrations (MICs) of five alternative antibiotics for H. pylori (rifaximin, rifabutin, furazolidone, garenoxacin, and sitafloxacin) using the agar dilution method and assessed mutations associated with antibiotic resistance using next-generation sequencing. Result: Analysis of 106 strains isolated from 1039 adult dyspeptic patients revealed that none of the strains were furazolidone-resistant. All strains were also sensitive to rifabutin and sitafloxacin. In contrast, the rates of resistance to rifaximin and garenoxacin were high (38.9% and 6.7%, respectively). The strains isolated from patients on Java Island had the highest resistance rates to garenoxacin and rifaximin. In addition, the resistance was distributed evenly among the ethnic groups, ranging between 25.0% and 69.2%. Except for rifaximin, for which the resistance rate was 38.9%, the other four antibiotics could be successfully employed to eradicate levofloxacin- and metronidazole-resistant H. pylori infections in vitro. Interestingly, garenoxacin-sensitive strains were found in regions with high clarithromycin resistance rates such as Bali and Papua Islands. In contrast, rifaximin might not be considered as an alternative antibiotic in regions with high clarithromycin resistance. There was an inconsistent association between gyrA and gyrB mutations and garenoxacin resistance. We confirmed that the I837V (replacement of isoleucine at position 837 with valine), A2414T/V, Q2079K and K2068R were the predominant rpoB point mutations. There was an association between vacA genotypes of H. pylori and rifaximin resistance (P = 0.048). Conclusion: furazolidone-, rifabutin-, and sitafloxacin-based therapies might be considered as alternative regimens to eradicate H. pylori in Indonesia, including regions with high metronidazole and clarithromycin resistance rates. Moreover, sitafloxacin but not garenoxacin should be considered for eradication of levofloxacin-resistant strains. Keywords: Indonesia; drug resistance; Helicobacter pylori; antibiotic

Diagnostic Value of 14C Urea Breath Test for Helicobacter pylori Detection Compared by Histopathology in Indonesian Dyspeptic Patients

Muhammad Miftahussurur,1,2 Adinta Windia,1 Ari Fahrial Syam,3 Iswan Abbas Nusi,1 Ricky Indra Alfaray,2,4 Kartika Afrida Fauzia,2,4 Hartono Kahar,5 Herry Purbayu,1 Titong Sugihartono,1 Poernomo Boedi Setiawan,1 Ummi Maimunah,1 Ulfa Kholili,1 Husin Thamrin,1 Amie Vidyani,1 Dalla Doohan,2 Langgeng Agung Waskito,2 Yudith Annisa Ayu Rezkitha,2,6 Gontar Alamsyah Siregar,7 Yoshio Yamaoka1,4 1Gastroentero-Hepatology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, 60286, Indonesia; 2Institute of Tropical Disease, Universitas Airlangga, Surabaya, East Java, 60115, Indonesia; 3Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta, 10430, Indonesia; 4Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, 879-5593, Japan; 5Department of Clinical Pathology, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, 60286, Indonesia; 6Faculty of Medicine, University of Muhammadiyah Surabaya, Surabaya, East Java, 60113, Indonesia; 7Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Sumatra Utara, Medan, 20155, IndonesiaCorrespondence: Muhammad MiftahussururGastroentero-Hepatology Division, Department of Internal Medicine, Faculty of Medicine, Dr. Soetomo Teaching Hospital, Universitas Airlangga, Jalan Mayjend Prof. Dr. Moestopo No. 6– 8, Surabaya, 60286, IndonesiaTel/Fax +6231-502-3865Email [email protected]: Histopathology method is often used as a gold standard diagnostic for Helicobacter pylori infection in Indonesia. However, it requires an endoscopic procedure which is limited in Indonesia. A non-invasive method, such as 14C Urea Breath Test (UBT), is more favorable; however, this particular method has not been validated yet.Patients and Methods: A total of 55 dyspeptic patients underwent gastroscopy and 14C-UBT test. We used Heliprobe® UBT for UBT test. As for the histology, May-Giemsa staining of two gastric biopsies (from the antrum and corpus) were evaluated following the Updated Sydney System.Results: The Receiver Operating Characteristics analysis showed that the optimum cut-off value was 57 with excellence Area under Curve = 0.955 (95% CI = 0.861– 1.000). By applying the optimum cut-off value, Heliprobe® UBT showed 92.31% for sensitivity, 97.62% for specificity, 92.31% for positive predictive value, 97.62% for negative predictive value, 38.77 for positive likelihood ratio, 0.0788 for negative likelihood ratio, and 96.36% for the accuracy.Conclusion: The 14C-UBT is an accurate test for H. pylori diagnosis with excellent sensitivity, specificity, and accuracy. The different optimum cut-off points suggested that a validation is absolutely necessary for new test prior application to the new population.Keywords: Helicobacter pylori, UBT, diagnostic, infectious diseas