h. pylori - assure.ppt

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The silent slayer of the gut



Hp is a gram negative bacillus responsible

for one of the most common infections

found in humans worldwide.

Became a link between chronic gastritis in

adults and malignancy, lymphoma and

adenocarcinoma



EPIDEMIOLOGY

In US, one third of the population is infected with Hp.

Internationally, varies with

- socioeconomic and country of origin

- higher in developing countries usually at younger age

Worldwide, more than 1 billion people are estimated to be

infected.

Race: Prevalence increased in African American, Hispanic,

Asian and native American population

Sex: Similar to males and females

Age: In developed countries, 10% <12 y/o, seropositivity rate

0.3- 1% per year.

*Triantafyllopoulou,M., MD, Northwestern University



Locally unpublished report states that:

Prevalence of 5.6% seropositivity rate in children and60% among 136 adult Filipino patients with dyspepsia

using the Clotest® (Cabahug et. al. 2003 and Caballero et

al., 1997, unpublished data).

A lower prevalence rate of 42% was reported by Daez et. al. in

2002 among 375 patients undergoing endoscopy at the

Philippine General Hospital utilizing the rapid urease test

and histopathology.

Laboratory diagnosis and susceptibility profile of Helicobacter pylori

infection in the Philippines,

Destura, Raul V., Published: 16 November 2004 Annals of Clinical Microbiology and Antimicrobials 2004, 3:25doi:10.1186/1476-0711-3-25



PATHOPHYSIOLOGY

• Spiral shape gram negative bacteria

• Highly motile because of multiple unipolar flagella

• Microaerophilic and potent producers of gastric urease

• Inhabits the mucus adjacent to the gastric mucosa

ADAPTIVE FEATURE THAT ENHANCES SURVIVAL

• Acidic environment

• Reduced oxygen requirement

• Adhesion molecules that are trophic to certain gastric cells



Suspected to produce disease factors such as:

urease (Induces IgG and IgA)

Vacuolating cytotoxin (induces inflammatory cytokines)

Catalase (for Hp survival by preventing reactive 02

metabolites from H202 in neutrophils)

LPS (enhances to colonize the stomach)



IMMUNOPATHOLOGY

Prominent Findings:

• Mucosa-Associated Lymphoid Tissue (MALT)and hyperplasia of submucosal lymphoid

nodules

• Increased acid secretory capacity andsensitivity to gastrin implicated in the

pathogenesis of duodenal ulcers



Variety of factors: Bacterial

Host Genetic

Environmental factors



Bacterial Factor

• Have two basic phenotypes based on the presence or absence of

vacuolating cytotoxin:VacA

–Cytotoxin –50% of bacterial strains have active cytotoxin activity

CagA

–High-molecular weight protein –Permits induction of cytokines, which aid in inflammation

Host factors

• Children may be better to clear infection than adults

• Hypochloridia allows to colonize in the stomach.



Genetic factors:

• Incidence of Hp infection increased in first-degree relatives of

children with duodenal ulcers.

• Concordance for ulcer disease is higher in monozygomatic than

in dizygomatic twins

Person to Person transmission

• Infection clusters within families and mother to child

• Crowding and poor hygiene (developing countries)



H. pylori infectioncauses chronic

superficial gastritis

Induces mononuclear

and polymorphonuclear cell infiltration of the

mucosa

Causes injury to

epithelial cells Urease cleaves urea into

cell-toxic ammonia



Immune response to infection:◦ Production of antibodies (local /systemic)

◦ Cell-mediated response

However, this immune response is ineffective in

clearing the infection Most H. pylori-infected persons do not develop

clinical symptoms

May be due to bacterial, host, and

environmental factors



Asymptomatic infection

Inflammation of the gastric mucosa (gastritis)

Dyspepsia

Gastric/duodenal ulcers



Associated with the development of:◦ Gastric adenocarcinoma

◦ Primary gastric non-Hodgkin’s lymphoma

◦ Mucosa-associated lymphoid tissue (MALT) lymphoma



Invasive tests requiring endoscopy- Biopsies and histology

- Rapid urease testing

- Bacterial culture- Polymerase Chain Reaction



DIAGNOSIS

Non-invasive tests

• Serum and whole blood antibody

• Saliva antibody

• Urine antibody

• Stool antigen

• Urea breath testing



DIAGNOSISINVASIVE TESTING

THROUGH ENDOSCOPY

ADVANTAGES DRAWBACKS

Biosies and histopathology Definitive diagnosis of H pylori,

severity of infection, topographic

distribution of gastritis

Requires sedation and anesthesia,

expensive, access of facilities and

expertise

Rapid Urease Testing of Biopsy

Tissues

Indirect identification of Hp within few

hours of endoscopy

Poor predictive value, dependent

on the number of tissue tested,

location of biopsy site, bacterialload, antibiotic intake, prevalence

Bacterial Culture To obtain a profile of antibiotic

sensitivity for a potential treatment

failure, for epidemiologic study

Low success rate for bacteria to

grow, expensive, no standardization

of culture, for research only

Polymerase Chain Reaction Highly sensitive that can be use in

body fluids, tissues. Molecular level to

detect the point mutation of antibiotic

and virulence form of Hp.

Expensive, difficult to set up,

specificity compromise by

contamination



DIAGNOSIS

NONVASIVE TESTINGTHROUGH ENDOSCOPY

ADVANTAGES DRAWBACKS

ELISA test for Hp Antibodies Not so expensive, easy to perform in

clinical setting, determine the

presence of IgG and IgM

Sensitivity & specificity is poor in

adults unless used in population

where initially developed

Saliva and Urine Tests for Hp Antibodies

Detects presence of IgG, painless,inexpensive, minimal labor

Protein concentration affectsresults, not yet commercially

available

Stool tests for Antigen Accurate in monitoring success of

eradication therapy

Patients reluctant to submit

specimen, cant be use refrigerated

specimen

Urea Breath Testing Test parameters are laboratory

specific, high sensitivity and specificity

both in adult and children

Requires ingestion of radiolabled14C-urea or urea tagged with stable

isotope 13C. Test influenced by

concurrent antibiotics & acid

suppression drugs, urease

producing organism.



Laboratory diagnosis and susceptibility profile of

Helicobacter pylori

infection in the Philippines

Destura, Raul V., Published: 16 November 2004 Annals of Clinical Microbiology

and Antimicrobials 2004, 3:25 doi:10.1186/1476-0711-3-25



Results:

- Sixty percent (60%) of the study population was positive for H.pylori infection (mean age of 44 years ± 13), 70% were

males.

- H. pylori culture showed a sensitivity of 45% (95% CI [29.5 –

62.1]), specificity of 98% (95%CI [81.5 –100%]),

- positive likelihood ratio of 19.93 (95% CI [1.254 –

317.04]) and a negative likelihood ratio of 0.56 (95% CI[0.406 – 0.772]).

-All H. pylori strains isolated were sensitive to metronidazole,

clarithromycin, amoxicillin and tetracycline.

Conclusion:Knowledge of the antibiotic susceptibility patterns allows more

cautious in the choice of first-line agents. Information on antibiotic

susceptibility profile plays an important role in empiric antibiotic

treatment and management of refractive cases



An ideal test for H pylori is noninvasive or

minimally invasive, highly accurate,inexpensive, and readily available and

enables differentiation between active or

past infection with the organism.

It is important to emphasize that the accuracy of

a diagnostic tests is greatly impacted by the

prevalence of H pylori in the population tested.

Gold et.al. Med. Position Statement: The North American Society for Pediatric

Gastroenterology & Nutrition. Nov. 2000. 31:490-497



ASSURE TM H. pylori RAPID TEST

Features:

Noninvasive

15 minute assay

Propriety Antigen

Three step assay

procedure

Sensitivity & specificity> 93%

Built-in procedural

control

Benefits

Accurate

High predictability of

current Infection

Quick result

No technical skills

needed

Suitable for children &

adults

Can use serum, plasma

or whole blood



ASSURE TM H. pylori RAPID TEST

Significance of IgG detection rapid test

• It is the long term responder.

• Determines either a long term chronic infection exists either treated or not.

• An indicative of a protective antibody from past infection that

was resolved.

• Present research studies indicate that a positive IgG is in fact

an ongoing infection provided patient was not treated for the last

6 months.

Principle of the test




Immunochromatographic assay

based

Specimen- Ab +

colloidal gold McAb

Chase buffer

RecAg protein

Control line

Protein marker for CI






based

Specimen- Ab +

colloidal gold McAb

Chase buffer

RecAg protein

Control line





FINDINGS OF THE STUDIES

• ASSURE Hp gave promising test performance in terms of

sensitivity and specificity of 94% (CI 86-98) and 90% (CI 80-

96), as compared to Assure step 71% (CI 59-80) and 90% (CI

80-96), respectively, for Chinese population.

• ASSURE Hp gave sensitivity and specificity of 94% and

93% with PPV of 95% and NPV of 91% and the test yielded

accurate result of 93% for Filipino population .



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h. pylori - assure.ppt

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