Management of Helicobacter pylori in Patients with Immune Thrombocytopenia

2019 ◽  
Vol 39 (03) ◽  
pp. 279-283 ◽  
Author(s):  
Yenny Alejandra Moreno Vanegas ◽  
Prakash Vishnu
Keyword(s):  
Helicobacter Pylori ◽  
Triple Therapy ◽  
Immune Thrombocytopenia ◽  
Response Rate ◽  
Immunosuppressive Agents ◽  
Complete Response ◽  
Platelet Response ◽  
New Therapeutic Approaches ◽  
Online Databases ◽  
H Pylori

AbstractThere is an association between Helicobacter pylori infection and immune thrombocytopenia (ITP), and few studies have suggested that eradicative treatment of H. pylori infection may improve platelet counts in patients with ITP. Conventional treatments for ITP include immunosuppressive agents, and more recently thrombopoietic agents. However, based on clinical reports of association between H. pylori and ITP, several medical societies increasingly suggest detection and eradication of H. pylori as a treatment for ITP. In this article, we reappraise recent medical literature to determine the effectiveness of platelet response after treatment of H. pylori infection in patients with ITP. We searched two online databases (MEDLINE and Google Scholar) for full articles published between January 2008 and May 2018, and found a total of 11 studies that presented data and outcomes of treatment of H. pylori infection in ITP patients. All the studies administered triple therapy (amoxicillin 500 mg, clarithromycin 250 mg and a proton-pump inhibitor each given twice daily for either 7- or 14-day course) for eradication of H. pylori. Median overall platelet response ranged from 27 to 69.2% with a complete response rate ranging from 0 to 65.4% and a partial response rate ranging from 0 to 29.4%. Although there is variability in the effectiveness between different populations, it appears to be of benefit to ITP patients with concomitant H. pylori infection when treated with triple therapy. However, further studies to understand the pathogenesis of H. pylori-associated ITP is necessary for the development of new therapeutic approaches for ITP.

scholarly journals Helicobacter pylori eradication affects platelet count recovery in immune thrombocytopenia

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ayoung Lee ◽  
Junshik Hong ◽  
Hyunsoo Chung ◽  
Youngil Koh ◽  
Soo-Jeong Cho ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
Complete Response ◽  
Long Term Effects ◽  
Infection Group ◽  
Platelet Recovery ◽  
First Line Therapy ◽  
H Pylori ◽  
Count Recovery

Abstract Helicobacter pylori (H. pylori) infection is on the rise as a cause of immune thrombocytopenia (ITP). It has been suggested that platelet recovery can be achieved following successful microbial eradication, although, the exact pathophysiology has yet to be fully elucidated. This study evaluated the long-term effects of H. pylori eradication monotherapy on platelet count recovery in patients with ITP. H. pylori eradication was analysed in 61 ITP patients. Patients who maintained a complete response (CR) for more than six months were classified as sustained responders (SR). The prevalence of H. pylori infection was 54.3% (75/138), and the success rate of eradication with first-line therapy was 71.4% (35/49). Patients who had achieved a CR at 2 months maintained a higher platelet count thereafter. At 1 year following eradication, platelet counts had increased 2.78 times in the eradicated group, 1.36 times in the sustained infection group, and 1.33 times in the no infection group compared with the baseline (P = 0.016).

Response to Treatment of Helicobacter Pylori in Patients with Immune Thromboctypenic Purpura: A Systematic Review and Metaanalysis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2151-2151 ◽  
Author(s):  
James B. Bussel ◽  
Allison Ostrow ◽  
Jodi B. Segal
Keyword(s):  
Helicobacter Pylori ◽  
Response Rate ◽  
Controlled Trial ◽  
Response Rates ◽  
Patient Data ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Platelet Response ◽  
Individual Level ◽  
H Pylori

Abstract Background: Patients with immune thrombocytopenic purpura (ITP) infected with Helicobacter pylori (H. pylori) are often treated with antibiotics to eradicate infection and raise platelet counts. We aimed to systematically review the evidence regarding this practice to better quantify response rate. Study Design and Methods: We searched MEDLINE through April 2005, without language restriction; reviewed reference lists and queried experts for articles describing treatment of ITP with antibiotics targeting H. pylori. We included studies of any design involving more than 5 patients. Response rates were tabulated using the authors’ definitions, and pooled using a random effects model. Techniques of meta-regression were used to assess whether patient or study characteristics influenced response rates. Results: We retrieved 52 potentially eligible studies. Of these, 16 studies met our inclusion criteria. From 10 studies, we had individual level patient data. None of the studies was a controlled trial. The pooled response rate (both partial and complete responses) was 45% [95% confidence interval (C.I.) 32% to 58%]. The number of previous treatments (0–1, 2, 3 or more) influenced the response rate with an 18% (p=0.001) decline in response rate with each higher category; duration of disease did not independently predict response. In analyses of individual patient data, quartile of platelet count upon entry also influenced response rate; 58% of patients in the highest quartile responded compared to 34% in the lowest quartile (p=0.018). Conclusions: No randomized controlled trial has tested H. pylori eradication with antibiotics as a treatment for ITP. The sixteen observational studies we reviewed were fairly consistent with approximately half of treated patients having a platelet response to therapy. Without control groups, these studies do not provide strong evidence to support practice recommendations. However, given the low toxicity of antibiotic therapy, this treatment may be appropriate for patients who have not demonstrated refractoriness to multiple therapies. Response Rates by Number of Previous Treatments Response Rates by Number of Previous Treatments

Effects of eradication of Helicobacter pylori infection in patients with immune thrombocytopenic purpura: a systematic review

Blood ◽  
2009 ◽  
Vol 113 (6) ◽  
pp. 1231-1240 ◽  
Author(s):  
Roberto Stasi ◽  
Ameet Sarpatwari ◽  
Jodi B. Segal ◽  
John Osborn ◽  
Maria Laura Evangelista ◽  
...  
Keyword(s):  
Systematic Review ◽  
Helicobacter Pylori ◽  
Platelet Count ◽  
Immune Thrombocytopenic Purpura ◽  
Response Rate ◽  
Complete Response ◽  
Helicobacter Pylori Infection ◽  
Thrombocytopenic Purpura ◽  
Overall Response ◽  
H Pylori

AbstractWhether the eradication of Helicobacter pylori infection can increase the platelet count in patients with immune thrombocytopenic purpura (ITP) is still a controversial issue. To provide evidence-based guidance, we performed a systematic review of the literature published in English, selecting articles reporting 15 or more total patients. We identified 25 studies including 1555 patients, of whom 696 were evaluable for the effects of H pylori eradication on platelet count. The weighted mean complete response (platelet count ≥ 100 × 109/L) and overall response (platelet count ≥ 30 × 109/L and at least doubling of the basal count) were 42.7% (95% confidence interval [CI], 31.8%-53.9%) and 50.3% (95% CI, 41.6%-59.0%), respectively. In 222 patients with a baseline platelet count less than 30 × 109/L, the complete response rate was 20.1% (95% CI, 13.5%-26.7%) and the overall response rate was 35.2% (95% CI, 28.0%-42.4%). The response rate tended to be higher in countries with a high background prevalence of H pylori infection and in patients with milder degrees of thrombocytopenia. These findings suggest that the detection and eradication of H pylori infection should be considered in the work-up of patients with seemingly typical ITP.

Moxifloxacin Based Triple Therapy as Alternative to Standard Therapy in Helicobacter Pylori Eradication.

2020 ◽  
Vol 18 ◽  
Author(s):  
Mohammed Hussien Ahmed ◽  
Sherief Abd-Elsalam ◽  
Aya Mohammed Mahrous
Keyword(s):  
Helicobacter Pylori ◽  
Triple Therapy ◽  
Therapy Group ◽  
Low Cost ◽  
High Rate ◽  
Helicobacter Pylori Eradication ◽  
Treatment Regimens ◽  
Group A ◽  
H Pylori ◽  
Group B

Introduction: Helicobacter pylori eradication remains a problematic issue. We are in an urgent need for finding a treatment regimen that achieves eradication at a low cost and less side effect. Recent published results showing a high rate of resistance and with clarithromycin-based treatment regimens. The aim of the study was to compare moxifloxacin therapy and classic clarithromycin triple therapy in H. pylori eradication. Methods: This was a pilot study that enrolled 60 patients with helicobacter pylori associated gastritis. Diagnosis was done by assessment of H. pylori Ag in the stool. The patients were randomly assigned to receive either moxifloxacin based therapy (Group A), or clarithromycin based therapy (Group B) for two weeks. We stopped the treatment for another two weeks then reevaluation for cure was done. Results: 90 % of patients had negative H. pylori Ag in the stool after 2 weeks of stoppage of the treatment in group A versus 66.7 % in Group B. None of the patients in both groups had major side effects. Conclusion: Moxifloxacin-based therapy showed higher eradication power and less resistance when compared to clarithromycin triple therapy.

scholarly journals Selective killing of Helicobacter pylori with pH-responsive helix–coil conformation transitionable antimicrobial polypeptides

2017 ◽  
Vol 114 (48) ◽  
pp. 12675-12680 ◽  
Author(s):  
Menghua Xiong ◽  
Yan Bao ◽  
Xin Xu ◽  
Hua Wang ◽  
Zhiyuan Han ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Triple Therapy ◽  
Helical Structure ◽  
Commensal Bacteria ◽  
Gastric Ulcers ◽  
Normal Tissues ◽  
Minimal Toxicity ◽  
Antimicrobial Polypeptides ◽  
H Pylori ◽  
Drug Resistant Strains

Current clinical treatment of Helicobacter pylori infection, the main etiological factor in the development of gastritis, gastric ulcers, and gastric carcinoma, requires a combination of at least two antibiotics and one proton pump inhibitor. However, such triple therapy suffers from progressively decreased therapeutic efficacy due to the drug resistance and undesired killing of the commensal bacteria due to poor selectivity. Here, we report the development of antimicrobial polypeptide-based monotherapy, which can specifically kill H. pylori under acidic pH in the stomach while inducing minimal toxicity to commensal bacteria under physiological pH. Specifically, we designed a class of pH-sensitive, helix–coil conformation transitionable antimicrobial polypeptides (HCT-AMPs) (PGA)m-r-(PHLG-MHH)n, bearing randomly distributed negatively charged glutamic acid and positively charged poly(γ-6-N-(methyldihexylammonium)hexyl-l-glutamate) (PHLG-MHH) residues. The HCT-AMPs showed unappreciable toxicity at physiological pH when they adopted random coiled conformation. Under acidic condition in the stomach, they transformed to the helical structure and exhibited potent antibacterial activity against H. pylori, including clinically isolated drug-resistant strains. After oral gavage, the HCT-AMPs afforded comparable H. pylori killing efficacy to the triple-therapy approach while inducing minimal toxicity against normal tissues and commensal bacteria, in comparison with the remarkable killing of commensal bacteria by 65% and 86% in the ileal contents and feces, respectively, following triple therapy. This strategy renders an effective approach to specifically target and kill H. pylori in the stomach while not harming the commensal bacteria/normal tissues.

Helicobacter pylori infection and chronic immune thrombocytopenic purpura: long-term results of bacterium eradication and association with bacterium virulence profiles

Blood ◽  
2007 ◽  
Vol 110 (12) ◽  
pp. 3833-3841 ◽  
Author(s):  
Giovanni Emilia ◽  
Mario Luppi ◽  
Patrizia Zucchini ◽  
Monica Morselli ◽  
Leonardo Potenza ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Chronic Gastritis ◽  
Immune Thrombocytopenic Purpura ◽  
Long Term Results ◽  
Platelet Response ◽  
Related Factors ◽  
Thrombocytopenic Purpura ◽  
Platelet Recovery ◽  
Chronic Immune Thrombocytopenic Purpura ◽  
H Pylori

AbstractEradication of Helicobacter pylori may lead to improvement of chronic immune thrombocytopenic purpura (ITP), although its efficacy over time is uncertain. We report the results of H pylori screening and eradication in 75 consecutive adult patients with ITP. We also used molecular methods to investigate lymphocyte clonality and H pylori genotypes in the gastric biopsies from 10 H pylori–positive patients with ITP and 19 H pylori–positive patients without ITP with chronic gastritis. Active H pylori infection was documented in 38 (51%) patients and successfully eradicated in 34 (89%) patients. After a median follow-up of 60 months, a persistent platelet response in 23 (68%) of patients with eradicated infection was observed; 1 relapse occurred. No differences in mucosal B- or T-cell clonalities were observed between patients with ITP and control participants. Of note, the frequency of the H pylori cagA gene (P = .02) and the frequency of concomitant H pylori cagA, vacAs1, and iceA genes (triple-positive strains; P = .015) resulted statistically higher in patients with ITP than in control participants. All asymptomatic H pylori–positive patients with ITP were suffering from chronic gastritis. Our data suggest a sustained platelet recovery in a proportion of patients with ITP by H pylori eradication alone. Overrepresentation of specific H pylori genotypes in ITP suggests a possible role for bacterium-related factors in the disease pathogenesis.

scholarly journals Helicobacter pylori eradication using tetracycline and furazolidone versus amoxicillin and azithromycin in lansoprazole based triple therapy: an open randomized clinical trial

2005 ◽  
Vol 42 (2) ◽  
pp. 111-115 ◽  
Author(s):  
Laura Cidrão Frota ◽  
Maria do Perpétuo Socorro Saldanha da Cunha ◽  
Carlos René Lima Luz ◽  
Antonio Haroldo de Araujo-Filho ◽  
Luciano A. S. Frota ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Triple Therapy ◽  
Protocol Analysis ◽  
Urea Breath Test ◽  
Test Results ◽  
Suitable Alternative ◽  
Helicobacter Pylori Eradication ◽  
Helicobacter Pylori Treatment ◽  
H Pylori ◽  
To Receive

BACKGROUND: Optimal anti-Helicobacter pylori treatment has not yet been established. AIM: To evaluate H. pylori eradication using tetracycline and furazolidone versus amoxicillin and azithromycin in lansoprazole based triple therapy in northeastern of Brazil. PATIENTS AND METHODS: One hundred and four patients with H. pylori infection, as determined by rapid urease testing and histology, were randomly assigned to receive either: lansoprazole (30 mg q.d.), tetracycline (500 mg q.i.d.), and furazolidone (200 mg t.i.d.) for 7 days (LTF; n = 52); or lansoprazole (30 mg b.i.d.) and amoxicillin (1 g b.i.d.) for 1 week, plus azithromycin (500 mg q.d.) for the first 3 days (LAAz; n = 52). H. pylori eradication was assessed 3 months following completion of therapy by means of rapid urease testing, histology and a 14C-urea breath test. RESULTS: H. pylori eradication was achieved in 46 of 52 (88.4%, 95% CI: 77.5%-95.1%) patients in LTF group and in 14 of 52 (26.9%, 95% CI: 16.2%-40,1%) patients in LAAz group. On a per-protocol analysis, eradication rates were 91.8% (95% CI: 81.4%-97.3%) and 28.5% (95% CI: 17.2%-42.3%), respectively in LTF and LAAz groups. CONCLUSION: The LAAz regimen yielded unacceptably low eradication rates. On the other hand, the LTF scheme represents a suitable alternative for H. pylori eradication.

scholarly journals Long Term Discontinuation of Eltrombopag after Remission in Primary Immune Thrombocytopenia: 8-Year Follow-up Data from 15 Spanish Centers

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2352-2352
Author(s):  
Tomas Jose Gonzalez-Lopez ◽  
Fernando Fernandez-Fuertes ◽  
Maria Cristina Pascual Izquierdo ◽  
Isabel Caparros ◽  
Silvia Bernat ◽  
...  
Keyword(s):  
Platelet Count ◽  
Median Time ◽  
Research Funding ◽  
Immune Thrombocytopenia ◽  
Previous Treatment ◽  
Complete Response ◽  
Platelet Response ◽  
Platelet Counts

Background: Successful discontinuation of eltrombopag in certain immune thrombocytopenia (ITP) patients after complete response has already been demonstrated. However, the frequency of this phenomenon and type of candidate patients are still matter of discussion. Moreover, possibility of long term discontinuation responses is not clearly established. Methods: Here we retrospectively evaluated our whole cohort of 508 adult patients (aged 18 years or more) with primary ITP treated with eltrombopag included in the Spanish Eltrombopag Registry with a focus on the patients who achieved a durable (at least six months) platelet response after stopping eltrombopag. Successful discontinuation of eltrombopag (SDOE) was defined as those patients who reached remission and maintained platelet counts ≥ 50x109/l for at least 6 months in absence of eltrombopag or any rescue therapies administered. Long term discontinuation of eltrombopag (LTDOE) was defined as those patients who reached remission and maintained platelet counts ≥ 50x109/l for at least 36 months in the absence of eltrombopag or any rescue therapies administered. The study was approved by the Hospital Universitario de Burgos Ethics Committee and fulfilled Helsinki declaration standards. Results: While 37.4% of our patients relapsed of ITP with subsequent platelet count drop sometime during first six months of discontinuation of eltrombopag, a total of 74 patients (14.6%) were able to achieve SDOE. The median age of SDOE patients was 62 [range, 47-79] years. There were 47 women and 27 men. According to the standard definition, patients were allocated to newly diagnosed (n=17), persistent (n=15) and chronic (n=42) ITP groups. The median time from diagnosis to eltrombopag initiation was 31 [range, 4-104] months. The median number of previous therapies was 2 [range, 1-2], including splenectomy (14%), rituximab (18%) and romiplostim (12%). As expected, all patients but 1 achieved a complete response (platelet count ≥100 x 109/L) prior to eltrombopag discontinuation The median duration of eltrombopag treatment was 7 [range, 2-19] months. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n=43), platelet count >400x109/L (n=16), aspartate aminotransferase elevation (n=5), diarrhea (n=4), thrombosis (n=3), patient's request (n=2) and other reasons (n=1). Analysis of these SDOE discontinued patients show that with a median follow-up of 55 [range, 29-79] months, 38 patients (51.3%) maintained treatment-free response 36 months after stopping eltrombopag with no need of additional ITP therapies (median time of eltrombopag discontinuation was 70 [range, 50-77] months).This condition is what we define now as LTDOE. Nevertheless, 36 patients relapsed beyond 6 months but before 36 months of eltrombopag discontinuation (median time of eltrombopag discontinuation was 10 [range,7 -22] months). Characteristics of LTDOE population were a median time since ITP diagnosis of 32 [range, 5-88] months with 15/38 patients having ITP <1 year. 9 patients (24%) were male and their median age was 50 [range, 37-64] years. They had received a median of only two previous treatment lines [range: 1-2 lines]. The median platelet count before starting eltrombopag was 19 x 109/L [range, 8-40]. Meanwhile, platelet count before eltrombopag stop was 218 x 109/L [range, 123-356]. The main characteristics (age, gender, duration of ITP, prior ITP lines, platelet count before starting eltrombopag, duration of eltrombopag treatment, and platelet count before eltrombopag withdrawal) of the 38 patients with LTDOE were compared with those of the SDOE cohort who did not achieve a LTDOE. Unfortunately, no predictive factors of LTDOE could be identified. Conclusion: Durable platelet response following eltrombopag cessation may be observed in only 15% of primary ITP patients treated with this drug. On the contrary, half of patients who achieve a sustained response after eltrombopag withdrawal will get a long term discontinuation. However, we are lacking predictor factors for successful and long-term discontinuation of eltrombopag in primary ITP. Disclosures Gonzalez-Lopez: Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau. Pascual Izquierdo:Novartis: Consultancy; Sanofi: Consultancy. Sánchez-González:Amgen: Consultancy, Speakers Bureau; Gilead: Speakers Bureau; Navartis: Consultancy, Speakers Bureau; Shire: Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Jarque:Takeda: Consultancy, Speakers Bureau; Shire: Consultancy, Speakers Bureau; Shionogi: Consultancy, Speakers Bureau; Servier: Speakers Bureau; Roche: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Grifols: Consultancy; Gilead: Consultancy, Speakers Bureau; CellTrion: Consultancy; Celgene: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Abbie: Consultancy, Speakers Bureau; Alexion: Consultancy, Speakers Bureau.

scholarly journals The efficacy and safety of quadruple therapy without bismuth (concomitant therapy) in the treatment of patients with Helicobacter pylori - associated gastric and duodenal peptic ulcer disease

2019 ◽  
Vol 91 (8) ◽  
pp. 28-33 ◽  
Author(s):  
A M Veliev ◽  
I V Maev ◽  
D N Andreev ◽  
D T Dicheva ◽  
A V Zaborovskii ◽  
...  
Keyword(s):  
Duodenal Ulcer ◽  
Helicobacter Pylori ◽  
Side Effects ◽  
Triple Therapy ◽  
Eradication Therapy ◽  
Test System ◽  
Efficacy And Safety ◽  
Concomitant Therapy ◽  
Quadruple Therapy ◽  
H Pylori

Aim. Evaluation of the efficacy and safety of quadrupletherapy without bismuth (concomitant therapy) in patients with Helicobacter pylori - associated gastric ulcer and duodenal ulcer in the framework of a comparative research in the population of patients in Russia. Materials and methods. A prospective randomized trial was conducted, which included 210 patients with H. pylori - associated gastric/duodenal ulcer without complications. During the process of randomization, the patients were divided into three equal groups (n=70) depending on the prescribed 10-day scheme of eradication therapy (ET): the first group received the classic triple scheme (Omeprazole 20 mg 2 times a day, Amoxicillin 1000 mg 2 times a day and Clarithromycin 500 mg 2 times a day); the second group received quadruple therapy with bismuth drugs (Omeprazole 20 mg 2 times a day, Tetracycline 500 mg 4 times a day, Metronidazole 500 mg 3 times a day, Bismuth subcitrate potassium 120 mg 4 times a day); the third group received quadruple therapy without bismuth - concomitant therapy (Omeprazole 20 mg 2 times a day, Amoxicillin 1000 mg 2 times a day, Clarithromycin 500 mg 2 times a day and Metronidazole 500 mg 2 times a day). Diagnostics of H. pylori infection during screening and control of eradication was carried out via the fast urease biopsy sample test and urea breath test system. Control of the effectiveness of ET of the microorganism was carried out not earlier than 4 weeks after the end of the treatment. During the course of therapy, the frequency of development of side effects was assessed using a special questionnaire. Results and discussion. The effectiveness of triple therapy was 72.8% (ITT; 95% CI of 62.17-83.54) and 78,4% (PP; 95% CI 68.19-88.72); quadruple therapy with the preparation of bismuth - 80.0% (ITT; 95% CI 70.39-89.6) and 84,8% (PP; 95% CI, 75.96-93.73); quadruple therapy without bismuth - concomitant therapy - 84.2% (ITT; 95% CI 75.54-93.02) and 92.1% (PP; 95% CI 85.43-98.94). Quadruple therapy without bismuth was reliably more effective than the classical triple therapy in the PP selection (p=0.044883). Statistical analysis showed a tendency to poorer effectiveness of ET in patients who had previously used antibiotic therapy (OR 0.4317; 95% CI 0.1776-1.049), and in individuals with a rapid metabolism genotype - CYP2C19*1/*1 (OR 0.12; 95% CI 0.005848-2.4624). The frequency of development of side effects during the use of triple therapy was 18.5% (95% CI of 9.23-27.91), when using quadruple therapy with bismuth - 20.0% (95% CI 10.39-29.6), and with the use of quadruple therapy without bismuth - concomitant therapy - 24.2% (95% CI 13.98-34.58). Conclusion. This prospective randomized study demonstrated the high efficiency of quadruple therapy without bismuth (concomitant therapy) in the framework of eradication of H. pylori infection in Russia.

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