1. H PYLORI BY MARUF A.

2. Historical Background  1982 - Marshall and Warren identified and subsequently cultured the gastric bacterium, Campylobacter pyloridis, later reclassified as Helicobacter pylori.  Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. [Lancet 1984 Jun 16;1(8390):1311-5 ]

3. Epidemiology & Bacteriology  The most common chronic bacterial infection in humans  The risk of acquiring H. pylori infection is related to socioeconomic status and living conditions early in life  developing nations: the majority of children are infected before the age of 10, the prevalence in adults peaks at more than 80 percent before age 50  developed countries: evidence of infection in children is unusual but becomes more common during adulthood.  Intrafamilial clustering  Possible hereditary susceptibility  Twin studies also support genetic susceptibility to infection

4. Epidemiology… Epidemiology…  Transmission — Route by which infection occurs remains unknown  transmission among persons sharing the same living environment  Person-to-person transmission of H. pylori through either fecal/oral or oral/oral exposure seems most likely.

5. Pathogenesis Pathogenesis  Helicobacter pylori is highly adapted to the gastric environment  pathophysiology of H. pylori infection and its eventual clinical outcome is a complex interaction between the host and the bacterium  Bacterial Factors: Urease production and motility- first step of infection Urease production and motility- first step of infection  Bacterial Attachment Three Hop proteins have been implicated in the pathogenesis of Three Hop proteins have been implicated in the pathogenesis of H. pylori infection, BabA (HopS), OipA (HopH), and SabA (HopP) H. pylori infection, BabA (HopS), OipA (HopH), and SabA (HopP) H. pylori can also bind to class II MHC molecules on the surface of gastric epithelial cells and induce apoptosis H. pylori can also bind to class II MHC molecules on the surface of gastric epithelial cells and induce apoptosis  Release of Enzymes Urease Urease phospholipases phospholipases Catalase Enzyme Catalase Enzyme Proteolytic Enzymes Proteolytic Enzymes Cag A & Vac A Cag A & Vac A

6. Pathogenesis HOST RESPONSE TO H. PYLORI  Infection induces a vigorous systemic and mucosal humoral response  Continuous gastric inflammation in virtually all infected persons - recruitment of neutrophils, followed by T and B lymphocytes, plasma cells, and macrophages, along with epithelial-cell damage  The gastric epithelium of infected persons has enhanced levels of interleukin-1b, interleukin-2, interleukin-6, interleukin-8, and tumor necrosis factor.  Some H. pylori–infected patients have an autoantibody response directed against the H+/K +ATPase of gastric parietal cells that correlates with increased atrophy of the corpus.

8. Clinical Outcomes  Variable  Influenced by microbial and Host factors  Responsible for the majority of DU & GU Ethiopian studies 1.Helicobacter pylori infection was detected in 93% of 174 patients with a peptic ulcer compared with 63% of 116 patients with normal findings (chi 2 = 37.3; P < 0.001) in a cohort of 834 consecutive patients examined by gastroscopy in Yirga Alem Hospital in south Ethiopia. [Trans R Soc Trop Med Hyg. 1999 Mar-Apr;93(2):171-3. ] 2.There were no statistically significant differences in the frequency of H. pylori seroprevalence between dyspeptic and non-dyspeptic patients [Ethiop.J.Health Dev. 2005;19(1):55-59] 2.There were no statistically significant differences in the frequency of H. pylori seroprevalence between dyspeptic and non-dyspeptic patients [Ethiop.J.Health Dev. 2005;19(1):55-59]

10. Clinical Outcome 1.Why some develop ulcers while others not ?  Host Genetics  polymorphism of IL-1 beta (and possibly IL-10 )- Determine the degree of inflammation

11. Clinical Outcomes H. pylori has been classified as a type I (definite) carcinogen since 1994. Gastric Ca Very strong Evidence Uemura N, Okamoto S, Yamamoto S, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med 2001;345:784-9. Gastric MALT Lymphoma   Significantly increases the risk   72 to 98 percent of patients are infected   Eradication alone induces regression of the lymphoma in 70 to 80 percent of cases. Br Med Bull 1998;54:79-85. Lancet 1995;345:1591-4.

12. Clinical Outcomes  GERD -some case–control and cohort studies have suggested that H. pylori infection may protect against GERD. - Recent Evidence: H. pylori eradication did not negatively influence relapse rates in patients with GERD. - Recent Evidence: H. pylori eradication did not negatively influence relapse rates in patients with GERD. [ Gastroenterology 2001;121:1120-6., Lancet 2001;358:1734]

13. Diagnostic Tests  Testing for H. pylori is recommended only if treatment is intended  infection can be diagnosed by noninvasive methods or by endoscopic biopsy of the gastric mucosa = UBT- H. pylori– derived urease activity in the stomach qualitatively detects active infection with a sensitivity and specificity of more than 90 percent. -Initial diagnosis of the infection and for follow-up of eradication therapy -Initial diagnosis of the infection and for follow-up of eradication therapy =serologic tests: cheap and widely used for the diagnosis of H. pylori infection in patients before treatment. -local validation is necessary -local validation is necessary =Stool Ag Tests: sensitivity -89 to 98% specificity -over 90% - suitable for follow-up - suitable for follow-up

14. Diagnosis =Endoscopic Biopsy  Patients with alarming symptoms, such as anemia, GI bleeding, or weight loss, >50 years of age. =urease test on an antral-biopsy specimen =urease test on an antral-biopsy specimen -Sensitivity 79 -100 % -Sensitivity 79 -100 % -Specificity 92 to 100 %. -Specificity 92 to 100 %. Ethiopian Study [ [Annals of TropicalMedicine & Parasitology, Vol. 98, No. 2, 181–189 (2004)]   Culture revealed H. pylori in only 69% of the patients. rapid urease tests- 71%, PCR–denaturating gradient gel electrophoresis -91%   histopathology- 81%   silver staining - 75%   stool-antigen tests -81%

15. Treatment  Indications 1.Indications for which treatment is strongly recommended  Duodenal or gastric ulcer (active or not, including complicated pepticulcer disease)  MALT lymphoma  Atrophic gastritis  Recent resection of gastric cancer  First-degree relative of patient with gastric cancer 2. Indications for which treatment is advised  Functional dyspepsia  Gastroesophageal reflux disease (in patients requiring long-term profound acid suppression) acid suppression)  Use of NSAIDs

16. Regimens  Proton-Pump-Inhibitor–Based Triple Therapies  Ranitidine Bismuth Citrate–Based Therapies  Bismuth-Based Triple Therapies

17. Second Line Therapy  Therapy is often associated with secondary antibiotic resistance  Retreatment should ideally be guided by data on susceptibility  quadruple therapies - a proton-pump inhibitor or an H2- receptor antagonist is added to a bismuth-based triple regimen with high-dose metronidazole  If a clarithromycin-based regimen is used first, a metronidazole-based regimen should be used afterward,or vice versa.  Rifabutin, given in association with amoxicillin and pantoprazole for 10 days, achieved an 86 percent rate of cure, even in patients with resistant strains

18. Ethiopian Study on Antimicrobial susceptibility  Susceptibility testing was performed on 50 clinical H. pylori isolates obtained from adult dyspeptic patients referred to the gastrointestinal (GI) Clinic of Tikur Anbassa University Hospital  all strains were sensitive to clarithromycin, erythromycin and tetracycline, while 38/50 (76%) and 3/50 (6%) of the strains were resistant to metronidazole and amoxicillin, respectively. [Ethiopian Medical Journal, 2004 (Vol. 42) (No. 2) 79-85] [Ethiopian Medical Journal, 2004 (Vol. 42) (No. 2) 79-85]