Treatment and Screening of H. Explain theories for the high - PDF document

1/12/2018 Learning Objectives – Pharmacist Treatment and Screening of H. • Explain theories for the high prevalence of H. pylori infection in pylori Infection in Alaskan Alaskan populations. • Discuss the risk factors for H. pylori Infection, appropriate screening, Populations and criteria for treatment. • Outline the similarities and differences for H. pylori treatment using Matthew F. Deraedt, Pharm.D. the current American College of Gastroenterology treatment Lieutenant United States Public Health Service guidelines and the Alaska Native Medical Center statewide guidelines. Alaska Native Medical Center Pharmacy Practice PGY-1 Resident • Differentiate post treatment testing methodologies and patient specific factors that predict H. pylori treatment success. Learning Objectives – Technician • Explain theories for the high prevalence of H. pylori infection in Alaskan populations. • Discuss the common signs and symptoms associated with H. pylori infection. No conflicts of interest to disclose. • Recognize medication regimens for the treatment of H. pylori infection. Pre-learning Assessment Pre-learning Assessment Which of the following symptoms are considered alert symptoms? Which of the following Alaskan patients would be candidates for endoscopy and possible H. pylori treatment? a. early satiety a. A 27 y/o male who presents with several weeks of dyspepsia b. post prandial belching secondary to eating c. unexplained weight loss b. A 60 y/o male who has recent weight loss and complaints of dyspepsia d. dyspepsia c. A 38 y/o male reports with several weeks of epigastric pain secondary eating d. A 57 y/o female who has daily ibuprofen use for osteoarthritis and reports dyspepsia 1

1/12/2018 Pre-learning Assessment Pre-learning Assessment What specific factors influence the treatment of H. pylori treatment in Which of the following are theories for the transmission of H. pylori ? Alaska versus the contiguous United States? a. fecal-oral a. > 60% prevalence among patient populations b. fomite associated b. high rate of resistance c. bodily fluids c. injudicious use of antimicrobials d. oral-oral d. crowded living considerations H. pylori H. pylori • Urease (+), Catalase (+), oxidase • Genus Helicobacter (+) • Gastric vs. Enterohepatic • Cryptic plasmids – not resistance • Helicobacter pylori associated • Microaerophilic • Genetic heterogeneity • Gram negative • Genetic rearrangement • Morphology • Rich G+C regions • Lawn formation • Spiral shaped • Rod • Poorly cultured • Coccoids (viable?) H. pylori on blood agar • Highly motile http://ngm.nationalgeographic.com/2013/01/125-microbes/oeggerli-photography#/06-helicobacter-670.jpg Kusters JG, et al. Clin MicroBiol Rev . 2006 Kusters JG, et al. Clin MicroBiol Rev . 2006 Koch’s Postulates – Theory Meets Practice Virulence Factors Mediate Pathogenesis • Warren observed spiral bacteria in gastric biopsies • Named them “ Campylobacter like organisms” • In 1985, Marshall ingested cultured bacteria and subsequently experienced gastritis • Marshall and Warren awarded The Nobel Prize in Physiology and Medicine in 2005 Kumar S. Textbook of Microbiology. 2012. Kusters JG, et al. Clin MicroBiol Rev . 2006 Kao CY, et al. Biomed J . 2016 39:14-23 Marshall BJ, et al. Med J Aust . 1985 2

1/12/2018 H. pylori intracellular modulation Presentation • Dyspepsia • Epigastric pain • Upper right or left quadrant • Worsens with eating • Post-prandial belching • Early satiety • Nausea • Reflux • Commonly associated with GERD https://www.mayoclinic.org Salama NR, et al. Nat Rev Microbiol . 2013;11(6):385-399. Kasper DL, et al. Harrison’s Principles of Internal Medicine. 19 th Edition Alarm Symptoms Implications of Non-treatment Alarm Symptoms • International Agency for New onset dyspepsia in patient ≥ 60 y/o Research on Cancer listed as a class I carcinogenic substance GI bleeding (hematemesis, melena, hematochezia, occult blood in stool) • Peptic ulcer disease Anorexia • Chronic gastritis Unexplained weight loss • Mucosa-associated lymphoid Dysphagia tissue (MALT) lymphoma Odynophagia • Adenocarcinoma of the stomach Vomiting GI cancer in 1 st degree relative Mcmahon BJ, et al. Epidemiol Infect. 2016.144:225 – 223. Helicobacter pylori infection and markers of gastric cancer risk Gastric Cancer Risk in Alaska Native Patients in Alaska Native persons: A retrospective case-control study • 5th most diagnosed cancer in AN • Mortality rate is three times what is seen in contiguous U.S . • Presence of a nti-H. pylori antibodies in patients with gastric cancer demonstrated a 2.63-fold increase in odds of cancer (P=0.01). https://www.nrcs.usda.gov Keck JW, et al. Can J Gastroenterol Hepatol. 2014:28(6):305-10 Keck JW, et al. Can J Gastroenterol Hepatol. 2014:28(6):305-10 3

1/12/2018 Transmission…a work in progress Transmission Hypothesis • Epidemiological data suggest • The fecal oral hypothesis oral-oral transmission or fecal- • Contaminated water sources oral transmission • H. pylori PCR studies • Recent studies suggest an • Oral – Oral hypothesis environmental reservoir • Supported by higher rate in cohabitation • Possible a combination? • H. pylori may be linked to • Environmental risk factors? hepatitis A infection (HAV) • Conflicting studies J Adv Research 2015;4(6):539 - 547 Krueger WS, et al. Epidemiol Infect. 2015;143:2520-31 J Adv Research 2015;4(6):539 - 547 Krueger WS, et al. Epidemiol Infect. 2015;143:2520-31 Leja M, et al. Heliconacter. 2016;21(1):3-7. Intermediate Hosts and Biofilm Formation Water as a reservoir? • Cellini et al. discovered a strain of • In Japan, Fujimura et al, compared three groups with different H. pylori in zooplankton drinking water sources • Reports of isolates producing • River water vs. ground water biofilms • Lower prevalence in ground water • Metabolically inactive • Insufficient N • Possibly persist in protozoa • Mazari-Hiriart et al . utilized 16S rRNA and cagA sequencing to • intermediate host microbiologyonline.org comment on H. pylori presence in drinking water • Reports of clinical strains producing • Detected DNA 16S rRNA 44% of sources and cagA gene 14% samples ordered biofilms • Positive PCR correlate to viable infectious matter? • Biofilms demonstrated through • Further Studies conducted by Bockleman et al. unable to find positive SEM in gastric mucosa samples PCR samples in water samples from Spain, Italy and Belgium. Fujimura S, et al. J Med Microbiol. 2008;57:909-10. Capon M, et al. J Gastrointest Surg . 2006;10(5):712-17. Bocklemann u, et al. Appl Environ Microbiol. 2009;75:154-63. Cellini L, et al. Appl Microbiol.2008;105:761-9 . http://ocean.si.edu Mazari-Hiriart M, et al. Plos One. 2008;3:e2305. Giao MS, et al. Appl Eviron Microbiol . 2008.;74:5898-904. Environmental Risk Factors Krueger et al. • Higher prevalence among infected family members • National Health and Nutritional Examination Survey • 1999 – 2000 • Acquisition rates are higher during childhood in developing countries • Examined for Environmental H. pylori risk factors weighted to than developed countries represent the U.S. population • Impoverished areas with overcrowding • Multivariable linear regression estimated an adjusted odds ratio and • Variable infection rates between developed vs. developing world and 95% confidence interval geographical regions Krueger WS, et al. Epidemiol. Infect. (2015), 143, 2520 – 2531. Krueger WS, et al. Epidemiol Infect. 2015;143:2520-31 4

1/12/2018 Krueger et al. conclusions High Risk Patients • Participants < 20 years of age • Risk factors agreed upon in the • Having well water (aOR 1.7, 95% CI 1.1 – 2.6) and living in a more crowded literature: home (aOR 2.3, 95% CI 1.5 – 3.7) • Low socioeconomic status • Participants ≥ 20 years of age • Increasing number of siblings • Infected parent – especially • Adults in soil-related occupations had significantly higher odds of mother seropositivity compared to those in non-soil-related occupations (aOR 1.9, • Men 95% CI 1.2 – 2.9) • Exposures to both well water and occupationally related soil increased the • Alaska Native/American Indian effect size of adults’ odds of seropositivity compared to non-exposed adults (aOR 2.7, 95% CI 1.3-5.6) Chey WD, et al. Am J Gastroenterology 2017 ;112:212-238. Krueger WS, et al. Epidemiol Infect. 2015;143:2520-31 Krueger WS, et al. Epidemiol. Infect. (2015), 143, 2520 – 2531. Application to Alaska Populations • Crowded living conditions • More time spent indoors What else makes treatment of H. pylori • Limited access to clean water unique in Alaska? • Overuse of antibiotics in remote areas • Access to specialty services http://www.alaskanative.net M. Bruce, et al. Public Health . 2016;137:5-12. High prevalence in AI/AN Rates of H. pylori infection in AN, 1980 - 1986 • Seropositivity • 40% worldwide for industrialized countries • 80 - 90% in developing nations • Alaska Natives • 75% overall • Ranges 64 – 81%, dependent on region • Puts treated individuals at high risk for reinfection… more later Parkinson AJ, et al. Emerging Infectious Diseases. 2000;7:885-888 Parkinson AJ, et al. Emerging Infectious Diseases. 2000;7:885-888 Tveit AH, et al. J Clin Microbiol. 2011;49(10):3638-43 Tveit AH, et al. J Clin Microbiol. 2011;49(10):3638-43 5