Case Study Clinical Case Summary History Helicobacter pylori Biochemical characteristics Transmission Epidemiology Global incidence of H. pylori infection risk factors for acquisition of H.pylori  Immune responses Pathogenesis Helicobacter pylori Virulence Factors Clinical Presentation Complications Peptic Ulcer Diagnosis Treatment Prevention

1. Dr. Murad Ibrahim
Miss Jumana Wadi
Prepared By:
Diaa M. Srahin
April, 2016
Al-Quds University
Faculty of Medicine
Microbiology

2. Case Study
A 50-year-old advertising executive consulted his primary health-care
provider because of tiredness, lethargy, and an abdominal pain centered
around the lower end of his sternum, which woke him in the early hours of
the morning. The pain was relieved by food and antacids. His uncle had
died of stomach cancer and he was worried that he had the same illness.
On examination his doctor noted that he seemed a bit pale and that he had
a tachycardia. His blood pressure was low. He was slightly tender in his
upper abdomen but there was no guarding or rebound tenderness.
The doctor took blood and feces samples and organized for an upper
gastrointestinal endoscopy. The full blood count showed a hypochromic
normocytic anemia with a hemoglobin of 8.9 consistent with iron
deficiency anemia. The gastroscopy showed a 3 cm ulcer in the prepyloric
region of the stomach (Figure 1). .The fecal antigen test for Helicobacter
pylori was positive. The patient was started on routine treatment for a
duodenal ulcer.

3. Clinical Case Summary
A 50- year-old male.
Chief Complain
 Abdominal pain centered around the lower end of his sternum.
Onset of the Pain
 On fasting.
Relieving Factors
 Food and Antacids.
Associated Symptoms
 Tiredness, Lethargy .
Family History
 His uncle had died of stomach cancer.

4. Clinical Case Summary
Physical Examination
 Tachycardia , Low BP , Tender in his Upper Abdomen and he
seemed a bit pale.
LAB. Investigations
Blood Test
 Iron deficiency anemia & hypochromic normocytic anemia.
Endoscopy
 3 cm ulcer in the prepyloric region of the stomach.
Stool Antigen test
 Fecal antigen test for Helicobacter pylori was positive.

6. Clinical Case Summary
Diagnoses
Peptic ulcer due to H. pylori infection.
Treatment
Patient was started on routine treatment for a duodenal
ulcer.

8. History
 Helicobacter pylori was first discovered in the stomachs of
patients with gastritis and ulcers in 1982, by Drs. Barry
Marshall and Robin Warren of Australia.
 This discovery have revolutionised the diagnosis, treatment and
prognosis of upper gastrointestinal disease.
 In recognition of their discovery, Marshall and Warren were
awarded the 2005 Nobel Prize in Physiology or Medicine.
 Its name refers to both its spiral shape (Helicobacter) and the
area of the lower stomach which it habitually colonizes: the
gateway (pylorus) between the stomach and small intestine.
 Formerly called Campylobacter pylori

9. Helicobacter pylori
 Helicobacter pylori is a non spore-forming, gram-
negative bacterium with a helical shape.
 curved forms occur and the bacillus also converts to a
coccoid morphology under environmental stress.
 It has multiple flagella at one pole ( 1 -5 ) and is
actively motile.
 Flagella play important role in motion and adhesion .

10. Helicobacter pylori
 H. pylori grows in an atmosphere of 5–15% oxygen,
5–12% carbon dioxide, and 70–90% nitrogen
(i.e. it is microaerophilic).
 H. pylori can survive in an acid environment for a
short time but is not an acidophile.
 Taking up to 5 days to grow on primary isolation and
producing small colonies (1–2 mm diameter) on
horse blood agar (5% horse blood in Columbia agar).

12. Biochemical characteristics
 H pylori is oxidase positive and catalase positive and is a
strong producer of urease.

14. Transmission
Entry into the body
 H. pylori enters via the mouth.
 In the stomach it can only survive for a short time before it is
killed by the acid.
 The presence of the enzyme urease on its surface protects it for
sufficient time before penetrate the mucus layer.
 The spiral shape, motility, and the production of phospholipases
and the ammonium ion (which affects the tertiary structure of
the mucus making it thin and watery) allow the Helicobacter to
penetrate the mucus layer very quickly.

15. Transmission (cont.)
 H. pylori can only adhere to gastric epithelial tissue, which is
found in the stomach and in the first part of the duodenum.
 The organism is found mainly in the antrum of the stomach but
can also be found in all parts of the stomach and duodenum.

16. Transmission (cont.)
Spread within the body
 It does not normally penetrate the gastric epithelium and enter the submucosal
layers and therefore remains restricted to the stomach and duodenum.
 Spread from person to person
 Spread is via the feco–oral route or oro–oral route.

17. Epidemiology
 Helicobacter pylori infection is well known to be the
most common human infection worldwide.
 Approximately 50% of the world's populations are infected
and that human beings are the main reservoir.
 The pattern of infection is an early childhood acquisition
of H. pylori (30%-50%) that reaches over 90% during
adulthood in developing countries.
 Infection in developed countries is less common in young
children and reaches up to 60% in older ages.

18. Epidemiology (cont.)
 H. pylori is the causative agent of chronic gastritis and peptic ulcer
diseases and is an important risk factor for the development of gastric
cancer and mucosal-associated lymphoid tissue (MALT) lymphoma.
 Although the world health organization (WHO) estimates indicate high
infection rates among the world populations, most infected subjects
develop no clinical symptoms or peptic ulceration and continue their
life with superficial chronic gastritis.
 However, still high percentages (approximately 17%) of the infected
subjects will develop peptic ulcers .
 one-quarter of such patients (approximately 4.25%) even experience
ulcer complications, and still fewer (1%) will progress to gastric
cancers.

19. Global incidence of H. pylori infection

21. Immune responses
 There is a strong innate immune response with infiltration by
granulocytes and macrophages (acute inflammation).
 Helicobacter avoids the innate immune response by inhibiting
phagocytosis. In some way, not yet clearly understood .
 There is a strong acquired immune response with antibody ;
local (stomach) and systemic antibodies of IgM, IgG, and IgA
class. but this is generally ineffective.
 Helicobacter avoids complement lysis by coating itself with
anti-complementary proteins such as CD59.

22. Pathogenesis
Main ways in which tissue damage can occur :
 Local damage caused by a vacuolating cytotoxin.
 The ammonium ion as a result of the urease activity, and the production
of phospholipase, which contribute to the formation of a poor quality
mucus barrier.
 Alteration of gastric physiology with enhanced acid production.
 Bystander damage is caused by release of free radicals from the
granulocytes.
 Autoimmunity – autoantibodies are induced by Helicobacter that
kill the acid-secreting parietal cells.
 Alteration of the balance of cell division and apoptosis.

24. Helicobacter pylori Virulence Factors
 Urease - enables the survival of H. pylori in a low pH environment
of the stomach lumen.
 Degrades urea to ammonia and carbon dioxide. Ammonia is alkaline
and neutralizes the acid fluid in the stomach.
 Flagella – allows penetration through viscous mucous layer where
conditions for growth are better.
 CagA – syringe-like structure that injects itself into host epithelial
cells.
 Activates signal transduction pathways and cell growth.
 Strains containing CagA have a higher inflammatory response and
higher risk for peptic ulcer and gastric cancer.

25. Helicobacter pylori Virulence Factors
 VacA – causes membrane channel formation, cell function interference,
and apoptosis.
 NAP – stimulates production of oxygen radicals from neutrophils
which damage cells.
 Adhesions and outer membrane proteins – BabA and HpaA
 LPS – contributes immune invasion by antigenic variation and
inhibition of somatostatin which regulate gastric acid production.
 Collagenase/Mucinase - causes damage to gastric epithelium by
degrading mucous components and exposing cells to gastric acid.

27. Clinical Presentation and Complications
 Most persons colonized by H. pylori will remain symptom-free .
 About 20% will go on to develop peptic ulcer disease and about
1% gastric cancer.
 H. pylori is a good example of a ‘slow’ infection, as infection occurs in
childhood but related diseases occur in adulthood.
 Ulcer disease presents with epigastric pain, heartburn or dyspepsia
or may be totally asymptomatic.
 Anemia (due to blood loss from the ulcer) and weight loss may also
occur
 Signs and symptoms of perforation (acute abdominal pain,
abdominal rigidity and guarding, rebound tenderness and shock).

28. Clinical Presentation and Complications
 H. pylori has a role in inflammatory bowel disease.
 H. pylori may be related to a wide range of extra-
gastrointestinal disease such as coronary heart disease,
stroke, migraine, idiopathic thromobocytopenic
purpura (ITP), rosaceae, and gallbladder disease.
 Some evidence exists for most of these but again there is
contrary evidence.

29. Clinical Presentation and Complications
 Most serious consequence of H. pylori infection is the development
of cancer.
 H. pylori is the Class I carcinogen which causes the majority of cases
of gastric adenocarcinoma (except that of the cardia of the stomach)
and MALT lymphoma.
 Clinical presentation of carcinoma is very nonspecific and is usually
associated with gastric ulcer rather than duodenal ulcer.
 carcinoma presents with abdominal pain or a mass with so-called
‘alarm symptoms’ weight loss and anemia.
 Gastric cancer originating at the cardia (gastro-esophageal junction)
does not appear to be related to colonization by H. pylori.

30. Peptic Ulcer
 Peptic ulcer disease refers to painful sores or
ulcers in the lining of the stomach or duodenum.
 Ulcer is the end result of an imbalance between
digestive fluids in the stomach and duodenum.
 Most ulcers are caused by an infection with
Helicobacter pylori (H. pylori).

31. Peptic Ulcer (cont.)
 The other major cause of ulcer disease is the usage of
nonsteroidal anti-inflammatory drug (NSAID).
 Other causes are Crohn’s disease and hypersecretory
states such as gastrinoma (Zollinger Ellison syndrome),
antral G cell hyperplasia, mastocytosis, and multiple
endocrine neoplasms (MEN-1).
 Acute stress ulcers are caused by excess alcohol use,
burns, trauma to the central nervous system, cirrhosis,
chronic pulmonary disease, renal failure, radiation, and
chemotherapy.

35. Diagnosis
These methods of diagnosis are usually performed in a research setting
or at a gastroenterology unit as they are invasive and expensive.
 Endoscopy and biopsy: the biopsy can then be cultured under micro-
aerobic conditions for H. pylori, which takes 5 days.
 Histology can demonstrate the characteristically shaped organism on the
surface of the epithelial cells and the inflammatory cell type can be identified.
 Rapid urease test (which involves putting one of the biopsies into a urea
solution with a pH indicator).
 Polymerase Chain Reaction (PCR) with appropriate primers:
16S rRNA, the urease gene (ure A, B or C), the flagella gene (flaA), the cagA
gene, and the vacA gene.

36. Diagnosis (cont.)
In primary care setting, diagnosis is by noninvasive tests, these are:
 Serology – the detection of IgG antibodies to H. pylori.
 Stool antigen test – immunoassay test that use either polyclonal or
monoclonal antibodies to detect the Helicobacter antigen in the feces.
 Urea breath test – this test is performed by giving the patient a drink
containing labeled urea (13C or 14C) and 20 minutes later collecting the breath
and measuring the amount of labeled CO2
 The cost-effective ‘Test & Treat’ policy – a person complaining of upper
gastrointestinal symptoms will be tested for Helicobacter and if positive
will be treated.
Recommended tests are urea breath test and the fecal antigen tests.
Anyone over 55 years or showing alarm symptoms must have an
endoscopy.

37. 1.Patient swallows a
labeled C13/14 urea
tablet. Dissolves to
release 14C-urea.
2.If present, H. pylori
metabolizes 14C-urea to
labeled carbon dioxide
(14CO2) and ammonia via
the enzyme urease.
3.14CO2 is transported in
the blood to the lungs.
4.Patient exhales. 14CO2 is
captured for analysis.
H2N(13/14CO)NH2 + H20 →
urease → 2NH3 + 13/14CO2
Urea Breath Test

38. Treatment
The concept that underlies the choice of drugs is to use antibiotics to
eliminate Helicobacter plus a drug to reduce gastric acidity.
Drugs that can suppress gastric acidity include :
 Proton Pump Inhibitors (PPIs) : These drugs stop acid from being
produced in the stomach. Some examples of PPIs are omeprazole
(Prilosec, others), esomeprazole (Nexium, others), lansoprazole
(Prevacid, others) and pantoprazole (Protonix, others).
 Histamine (H-2) blockers : These medications block a substance
called histamine, which triggers acid production. Examples include
cimetidine (Tagamet) and ranitidine (Zantac).
 Bismuth subsalicylate (Pepto-Bismol) : This drug can be used in the
treatment, it works by coating the ulcer and protecting from stomach
acid.

39. Treatment (cont.)
 Many antibiotics can be used to kill H. pylori in the stomach,
such as :
- Amoxicillin
- Clarithromycin (Biaxin)
- Metronidazole (Flagyl)
- Tetracycline (Sumycin)
- Tinidazole (Tindamax)
- Levofloxacin
 Two antibiotics are generally recommended, in order to reduce
the risk of treatment failure and antibiotic resistance.
 There are increasing numbers of patients with H. Pylori
infection that is resistant to antibiotics, so it is important to
take all the medications prescribed and to have a test that
confirms that the infection has been cleared.

40.  The table shows lists of initial recommended regimens for H. pylori
eradication according to the American College of Gastroenterology.
note, not all of the recommendations are FDA approved.

41. Prevention
 There is no vaccine or other specific preventive measure for H. pylori.
 Successful vaccine has been produced in animal models, a vaccine does not
yet exist for Helicobacter in humans. This might be due to the fact that
appropriate ‘protective’ antigens have not yet been defined for human disease.
 Improvement of public health standards in developing countries may help
to decrease the incidence of transmission.
 Do not eat poorly cooked food.
 Avoid unsanitary areas.
 Wash your hands thoroughly.
 Eat in sanitary places.
 Stop interacting with those infected.
 Get tested.
 Get adequate nutrition.