What is the Value of Noninvasive Testing for Active Infection?

1
What is the Value ofNoninvasive Testing for
ActiveInfection?
Understanding the Diagnosisof H. pylori

• Syed Wahab, M.S.
• Department of Pathology
• Forum Health, Northside Medical Center1

2
Clinical and Economic Impact of PUD H. pylori
Infection.

• More than 25 million Americans will develop
  peptic ulcer disease (PUD) at some point during
  their lifetime
• 700,000 Endoscopies every year
• H. pylori is associated with gt80 of duodenal
  ulcers
• 3.8 Million Prescriptions/ year
• PUD costs approximately 6 billion annually in
  the US

3
H. pylori Bacteria

• Gram negative
• Spiral rod
• Unipolar flagella
• Microaerophilic
• Urease positive
• Most important
• character

Scanning microscopic view of H. pylori
4
H. Pylori Gastric biopsy
H E stain
H. pylori immunostain
5
H. pylori Infection

• Transmissible
• Oral-oral and oral-fecal
• Infects the human stomach
• Produces inflammatory response
• This brings up the point of the importance of
  hand washing

6
H. pylori Infection

• The bad news
• High morbidity
• Chronic and acute gastritis
• Peptic ulcers
• Gastric cancer
• Classified by WHO as a Class I carcinogen

7
H. pylori Infection

• The best news is
• It is curable

8
Indications for H. pylori testing

• Dyspepsia in primary care setting.
• Documented gastric and duodenal ulcer.
• History of peptic ulcer.
• Gastric Mucosa-Associated Lymphoma.
• After resection of early gastric adenocarcinoma.
• First-degree relative of a patient with gastric
  cancer.

9
Outcomes of H. pylori Infection

• Often asymptomatic (latent), but not benign,
• with progressive gastric damage1
• Dyspepsia1
• PUD2 duodenal and gastric ulcers (17)
• Life-threatening complications occur in 1-2 of
  patients with peptic ulcer disease per year
• Gastric cancer3
• Mucosa-associated lymphoid tissue (MALT)/primary
  gastric B-cell lymphoma3

1. Malfertheiner P et al. Aliment Pharmacol Ther.
200216167. 2. Nomura A et al. Annals of Int
Med. 1994120977. 3. Parsonnet J et al. N Engl J
Med. 19943301267.
10
Outcomes of H. pylori Infection

• Latest research suggests
• 45 of babies with Colic have H. pylori.
• Eradication of H. pylori in Glaucoma improved
  eyesight significantly.
• H. pylori is involved in some cardiac conditions.
  

11
H Pylori Disease Associations

• Migraine Headaches
• Glaucoma
• Stroke
• Morning Sickness
• SIDS
• Negative Cardiac Assesments

12
Prevalence of H. pylori Infection

• Varies geographically
• May be as high as 52 in the U.S.
• 80-90 in developing countries.

Graham DY et al. Gastroenterology. 19911001495.
13
Prevalence of H. pylori Infection

• 50 of people over 60 years of age and 8-20 of
  those younger than 60 are infected
• High prevalence in minorities and immigrants from
  developing countries
• Vaira et al, Diagnosis of Helicobacter pylori
  infection with a new non-invasive antigen-based
  assay. The Lancet, Vol 354, July 3, 1999.

14
H. pylori Infection Risk Factors

• Low socioeconomic status
• Crowded or unsanitary living conditions
• Born in a developing country
• Born before 1950
• Children in the family
• Exposure to gastric contents
• Nurses
• Endoscopists

Graham DY et al. Gastroenterology. 19911001495.
15
Current Trends in Management of Dyspepsia

• Undifferentiated dyspepsia
• Empiric trial of H2 blocker or
• Proton Pump Inhibitor (PPI)
• Symptoms persist?

Meurer LN, Bower DJ. Am Fam Physician.
2002651327.
16
Recommended Management of Dyspepsia

• Undifferentiated dyspepsia
• Empiric trial of H2 blocker or
• Proton Pump Inhibitor (PPI)
• Symptoms persist?

Yes Test for H. pylori
Positive Eradication therapy
Negative GI referral or long-term PPI therapy
Meurer LN, Bower DJ. Am Fam Physician.
2002651327.
17
Problems with CurrentManagement of Dyspepsia

• Many patients with dyspepsia are infected with H.
  pylori 1
• PPIs mask the symptoms of H. pylori they do not
  cure the underlying disease2,3
• PPIs may worsen corpus histology2,3
• Cure reduces healthcare costs by avoiding further
  morbidity and mortality4
• 90 of patients with PUD do not experience a
  recurrence after H. pylori eradication

1. Talley NJ et al. Aliment Pharmacol Ther.
1999121135. 2. Graham DY, et al. Aliment
Pharmacol Ther. 200317193 . 3. Larkin CJ, et
al. Scand J Gastroenterol. 200035578. 4.
Sonnenberg A, Townsend WF. Arch Intern Med.
1995155922.
18
Recommended Management of Dyspepsia

• Undifferentiated dyspepsia
• Empiric trial of H2 blocker or
• Proton Pump Inhibitor (PPI)
• Symptoms persist?

Yes Test for H. pylori
No Routine follow-up
Positive Eradication therapy
Negative GI referral or long-term PPI therapy
Meurer LN, Bower DJ. Am Fam Physician.
2002651327.
19
Indications for Noninvasive Testing for H. pylori

• Strongly Recommended
• Dyspepsia
• History of/active peptic ulcer disease
• Gastric MALT lymphoma
• Following gastric cancer resection
• Following peptic ulcer surgery
• First-degree relative with gastric cancer
• Long-term Non-steroidal anti-inflamatory drugs
  (NSAID) therapy

In the absence of alarm signs for gastric
cancer or ulcer disease 1. Malfertheiner P, et
al. Aliment Pharmacol Ther. 200216167. 2.
Talley NJ et al. Aliment Pharmacol
Ther. 1999121135.
20
Indications Noninvasive Testing for H. pylori
(cont.)

• Advisable
• Family history of duodenal ulcer
• Family members with H. pylori infection
• GERD requiring long-term PPI therapy

In the absence of alarm signs for gastric
cancer or ulcer disease Malfertheiner P, et al.
Aliment Pharmacol Ther. 200216167. 2.Talley NJ
et al. Aliment Pharmacol Ther. 1999121135.
21
Why Test Patients with GERD?

• Reflux symptoms have been shown to improve when
  H. pylori is eradicated1
• Patients with GERD and H. pylori infection
  experience decreased frequency of hospital visits
  and use of antiacid medications when H. pylori is
  eradicated1
• Prevents exacerbation of corpus gastritis by PPIs
  in patients with H. pylori 2,3

1. Miwa H, et al. Helicobacter. 20027219. 2.
Graham DY, et al. Aliment Pharmacol Ther.
200317193 3. Larkin CJ, et al. Scand J
Gastroenterol.200035578.0
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Why Test Chronic NSAID Users?

• NSAID use can cause gastric mucosal injury H.
  pylori predisposes to increased damage from
  NSAIDs1-4
• H. pylori infection increases the risk of an
  NSAID ulcer complication 2-4 fold4
• H. pylori eradication in chronic NSAID users is
  suggested5

1. Chan FK, et al. Lancet. 1997350975. 2.
Feldman M, et al. Am J Gastroenterol.
2001961751. 3. Chan FK, et al. New Engl J Med.
2001344967. 4. Huang JQ, et al. Lancet.
200235914. 5. Malfertheiner P, et al. Aliment
Pharmacol Ther. 200216167.
23
Suggested Guidelines forTreatment of Patients
with GI or Ulcer Disease
History Physical Exam
Peptic ulcer disease
Undifferentiated dyspepsia
Symptoms of GERD
Use of NSAIDs or aspirin
Test for H. pylori
Positive Eradication therapy Confirmation of
cure
Malfertheiner P, et al. Aliment Pharmacol Ther.
200216167.
24
Suggested Guidelines forTreatment of Patients
with GI or Ulcer Disease
History Physical Exam
Peptic ulcer disease
Undifferentiated dyspepsia
Symptoms of GERD
Use of NSAIDs or aspirin
Test for H. pylori
Positive Eradication therapy Confirmation of
cure
Negative Treat for PUD, Initiate PPI therapy, or
discontinue NSAIDs
Malfertheiner P, et al. Aliment Pharmacol Ther.
200216167.
25
Types of H. pylori Tests

• Endoscopy
• Rapid urease tests
• Histology
• Culture
• Serologic (antibody)

• Stool antigen tests
• 13C Urea blood test
• Urea breath tests
• 14C-urea
• 13C-urea

Malfertheiner P, et al. Aliment Pharmacol Ther.
200216167.
26
Endoscopy

• Histology is often considered a gold standard for
  detection of H. pylori infection1,2
• Used for patients with symptoms of complicated
  ulcer, alarm symptoms, or long-standing GERD to
  rule out Barretts esophagus1,3
• Invasive1-3
• Costly1

1. Meurer LN, Bower DJ. Am Fam Physician.
2002651327. 2. Cutler AF et al.
Gastroenterology. 1995109136. 3. Chey WD.
Practical Gastroenterol. 2001April28.
27
Serology

• Serum antibody tests
• Detect antibodies to present or past H. pylori
  infection1
• Cannot distinguish between active and past
  infection2
• Pretest probability is critical for
  interpretation1,3,4

1. Loy CT et al. Am J Gastroenterol.
1996911138. 2. CheyWD, Fendrick AM. Arch Intern
Med. 20011612129. 3. Vaira D, Vakil N. Gut.
200148287. 4. Cutler AF et al. Gastroenterol.
1995109136.
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Stool Antigen Test

• Detects H. pylori protein antigens as the marker
  of infection1
• Detects active infection1
• Compliance issues2
• Recommended in Maastricht 2-2000 Consensus
  Report3

1. Matsuda M, et al. J Gastroenterol.
200338222. 2. Chey WD. Practical Gastroenterol.
2001April28. 3. Malfertheiner P et al. Aliment
Pharmacol Ther. 200216167.
29
HpSATM Microtiter wells and HpSATM Immunocard
kits.
30
HpSATM Microtiter wells
31
HpSATM Immunocard
Test Sample
Control Line (Green)
Test Line (Red)
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14C Urea Breath Test

• Measures urease activity using
• 14C isotope1,2
• Detects active infection1,2
• Radioactive1,2
• Not recommended for women of childbearing age1,2
• H2 blockers affect test reliability3
• Not approved for post-treatment monitoring3

1. CheyWD. Practical Gastroenterol.
2001April28. 2. Peura DA et al. Am J
Gastroenterol. 199691233. 3. PYtest
prescribing information. 1997.
33
13C Urea Blood Test

• Detects active infection1,2
• Nonradioactive1,2
• Requires mass spectrometer2
• Gray zone in which positive and negative cannot
  be distinguished2
• 5-10 false-negative rate2

1. CheyWD. Practical Gastroenterol.
2001April28. 2. Ez-HBT prescribing
information. 2003.
34

• Test for the Active Disease
• and the Cure

35
13C Urea Breath Test

• Detects active infection
• Sensitive and specific
• Non-radioactive
• No special handling requirements
• Easy to collect and handle sample
• Not indicated in pediatric population

1. Graham DY et al. Am J Gastroenterol.
2001961741. 2. Leodolter A et al. Am J
Gastroenterol. 1999942100.
36
Tests for H. pylori InfectionActive vs.
Serology Testing
Active Disease Testing
37
Tests for H. pylori InfectionActive vs.
Serology Testing
Patient management More
cost-effective
250 200 150
30 25 20
Dollars
Total Patients
Active disease test Serology test
Active Testing Antibody Testing
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Summary RegardingH. pylori Testing

• Testing for H. pylori in patients who have
  symptoms or are at risk for H. pylori reduces
  health care costs by preventing further morbidity
• Several noninvasive tests for H. pylori infection
  are available
• Tests can be categorized as detecting
• active infection or identifying presence of
  antibodies against H. pylori

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Suggested Steps in Management of H. pylori

• Diagnosis
• Therapy
• Confirm cure

Malfertheiner P, et al. Aliment Pharmacol Ther.
200216167.
40
Confirmation of Cure ofH. pylori Infection

• Active tests must be used
• Cannot use serology
• Risks of not testing
• Recurrent ulcer
• Ulcer complications, gastric cancer
• Transmission to others

Chey WD. Practical Gastroenterol. 2001April28.
41
HpSA vs. UBT
42
HpSA vs. UBT
Accuracy relative to gold standard
Excellent
Excellent
Drinking an Isotopic Carbon (C13) solution
Yuck factor
Collecting stool
Stability of specimen
1-2 days at R.T.
7 days
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Conclusions

• H. pylori is a transmissible, infectious disease
  with potentially serious outcomes
• H. pylori infection may be asymptomatic or cause
  dyspepsia
• Eradication therapy can cure H. pylori infection
  and prevent morbidity and downstream events such
  as PUD and gastric cancer
• Patients with symptoms of upper-GI disease, and
  who use aspirin or NSAIDs should be tested for H.
  pylori infection

44
Conclusions (cont.)

• Several noninvasive tests to detect H. pylori
  infection are available
• Categorized as detecting active infection or
  identifying the presence of antibodies against H.
  pylori
• Active tests of infection are required for
  post-treatment confirmation of cure of H. pylori
  infection

45
H. Pylori testing

• Before I end
• Thanks to Dr. Ortega for the invitation.
• Thanks to Meretek and Meridian for helping in
  this presentation.
• And a special thanks to Mindy Borowski.
• Thanks to all of you for being here.

46
References

• Meridian research
• The prevalence of H.pylori in peptic ulcer
  disease. Aliment Pharmacol Ther.1995.
• CDC H.pylori fact sheet, www.cdc.gov
• Fendrick, Mark et al, Guide to diagnosing
  H.pylori infection in primary care, Health
  Communications, 1998.
• Goldstein et al, Reduced Risk of upper
  gastroenterological ulcer complications with
  celecoxib, a novel COX-2 inhibitor, Am J G
  2000951681-690.
• Marshland, DW et al, Content of Family Practice.
  J Fam Prac 1976 337-68.
• National Institute of Diabetes and Digestive and
  Kidney Disorders, NIH Pub. No. 95-38 Jan 1995.