Upload
rujean-romy-guisando
View
239
Download
1
Embed Size (px)
Citation preview
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 1/33
The silent slayer of the gut
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 2/33
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
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 3/33
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
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 4/33
Locally unpublished report states that: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al., 1997, unpublished data).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
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 5/33
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 6/33
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 7/33
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
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 8/33
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)
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 9/33
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
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 10/33
Variety of factors: Bacterial
Host Genetic
Environmental factors
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 11/33
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.
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 12/33
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)
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 13/33
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
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 14/33
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
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 15/33
Asymptomatic infection
Inflammation of the gastric mucosa (gastritis)
Dyspepsia
Gastric/duodenal ulcers
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 16/33
Associated with the development of:◦ Gastric adenocarcinoma
◦ Primary gastric non-Hodgkin’s lymphoma
◦ Mucosa-associated lymphoid tissue (MALT) lymphoma
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 17/33
Invasive tests requiring endoscopy- Biopsies and histology
- Rapid urease testing
- Bacterial culture- Polymerase Chain Reaction
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 18/33
DIAGNOSIS
Non-invasive tests
• Serum and whole blood antibody
• Saliva antibody
• Urine antibody
• Stool antigen
• Urea breath testing
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 19/33
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
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 20/33
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.
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 21/33
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
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 22/33
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
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 23/33
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
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 24/33
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 25/33
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
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 26/33
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
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 27/33
Principle of the test
Immunochromatographic assay
based
Specimen- Ab +
colloidal gold McAb
Chase buffer
RecAg protein
Control line
Protein marker for CI
Principle of the test
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 28/33
Principle of the test
Immunochromatographic assay
based
Specimen- Ab +
colloidal gold McAb
Chase buffer
RecAg protein
Control line
Protein marker for CI
Principle of the test
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 29/33
Principle of the test
Immunochromatographic assay
based
Specimen- Ab +
colloidal gold McAb
Chase buffer
RecAg protein
Control line
Protein marker for CI
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 30/33
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 31/33
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 32/33
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 .
7/28/2019 H. pylori - ASSURE.ppt
http://slidepdf.com/reader/full/h-pylori-assureppt 33/33
… to save time
… to save lives