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jeudi 1 décembre 2011

HELICOBACTER PYLORI AND GASTRITIS, GASTRIC CANCER AND ULCER

Helicobacter pylori & Gastritis, 

Gastric Cancer and Ulcer

Helicobacter pylori, ulcer, gastric or stomach cancer, gastritis, Nobel Prize

Due to the high number of company executives and CEOs as victims of ulcer, the disease was considered chronic related to stress and lifestyle. Later on with the commercial success of proton pump inhibitors like Tagamet, Prilosec, Nexium the interest in the R&D of ulcer and GI tract shifted to other promising areas. It took almost 100 years from the discovery of the bacteria to acceptance of its role in the gastric diseases. The chance discovery of Helicobacter pylori in biopsy samples from victims of ulcer by Warren and later the isolation and culture of the bacteria with Marshall in 1982. The award of the Nobel prize in 2005 was a recognition of the role played by Helicobacter pylori in 90% of cases of duodenal ulcers and 80% of gastric ulcers. About 50% of humans are infected and 10-15% develop ulcer and gastritis. A few % develop gastric cancer. These infectious diseases can be cured by antibiotics in combination with proton pump inhibitors.

Table des matières



Salim Djelouat
Professor Medical Analyses and Medical bacteriology / Scientific Author / knolAuteur
Krishan Maggon
Consultant Pharmaceutical Biotechnology R&D & Advisor, Geneva, Switzerland & New York, USA
 
Knol Publishing Guild (KPG)
Serving the publishing aspirations of Knol writers, Planet Earth
 
 
 
CE KNOL A REÇU LA MÉDAILLE D'OR



http://www.helico.com/disease_duo.html


1 - INTRODUCTION  

    The genus Helicobacter belongs to the Campylobacter family, part of the spiral bacteria in the digestive tract. 
    It has the characteristics of spiral bacteria in the digestive tract, namely:  

• A spiral shape or curved 
• A micro aerobic metabolism and not using the sugar to draw its energy. 
• An ecological system, adapted to life in the mucus.  

    It is individualized on genetic criteria: branch of Proteobacteria. 
    There are many species of Helicobacter, gastric some, others say enterohepatic liver.


2 - HISTORY 

Robin Warren in 1979 first observed the bacteria in 50% of biopsy samples from patients who had died due to ulcer. A new biopsy study was done by Barry Marshall and Robin Warren in 100 Australian patients to confirm the earlier findings. The bacterium was isolated and cultured for the first time in 1982, Helicobacter pylori, bacteria on the surface of the gastric mucosa, are able to survive and persist in spite of gastric acidity and the strong immune response.  They showed that drinking a solution of the bacterium caused strong stomach reaction and it was identified as a cause of chronic inflammatory diseases such as gastroduodenal ulcer disease.  
This milestone discovery was largely ignored as ulcer were easily cured by 1-2 weeks treatment with proton pump inhibitors like Tagamet, Zantac, Prilosec and Nexium. It was only several years later than the merits of it were widely accepted, especially in Europe and France in 1995. 

From Royal Perth Hospital 

2005 Nobel Laureates, Professor Barry Marshall (left) and Dr Robin Warren (right)

2005 Nobel Laureates, Professor Barry Marshall and Dr Robin Warren
  

3 - HABITAT  

    Helicobacter pylori bacterium is a "strictly" human being transmitted to young children mainly in the family.  It infects about 50% of humans and probably transmitted from mother to child during birth. About 10-15% of the infected persons develop ulcers and a few % develop stomach cancer. The incidence is higher in developing countries and poor communities.

It lives exclusively in the human stomach (to date, Helicobacter and the only known organism that can live in an environment as acid as the stomach). Studies indicate that water can be a possible source of transmission of Helicobacter pylori. These studies have shown that this bacterium can live in water and supported by changes in temperature from 39.2°F to 59°F.

Image Electron Micrograph of Helicobacter pylori
Source 

File:EMpylori.jpg




4 - EPIDEMIOLOGICAL STUDY

    The bacteria probably spread directly from person to person orally.
    Everything is played during childhood: if an individual is not infected before the age of 10 years, he has very little risk of being later.

    Helicobacter pylori are found in more than 90% of people with duodenal ulcers and in about 80% of those with gastric ulcer.
     Infection with Helicobacter pylori is one of the most chronic infections throughout the world: 20 to 90% of adults are infected in different countries.

    The infection is more common in developing countries (60 to 80% of the population affected), while it is lowest in the industrialized countries (20 to 50% of the population that is affected, especially those disadvantage). 
A sharp rise in the elderly population is observed. The infectious dose for humans colonize remains unknown, but we suppose it is very low and given the high percentage of people infected.
 
 

5 - NATURAL PATHOGEN  

Infection with Helicobacter pylori is acquired in childhood
In majority of infected individuals, chronic gastritis evolves without any clinical symptoms and remains asymptomatic.
The lesion therefore basic infection is Helicobacter pylori gastritis, i.e. an inflammation of the gastric mucosa with a histological definition.
This always occurs when gastritis Helicobacter pylori is present.
It can persist for decades or even the whole life of the subject except in cases of intercurrent treatment.In those cases, it can progress to the following diseases:
 
    A - Gastric and Duodenal Ulcer:  
 
    Infection with Helicobacter pylori may develop in approximately 5% of cases, to the ulcer disease, once considered psychosomatic origin.  
    It will weaken the mucous becomes sensitive to acid.  
    The eradication of Helicobacter pylori is an effective cure for ulcer.
 
Images from The Helicobacter Foundation
Incidence of H.pylori infections correlates with the socioeconomic development of countries and populations

Image of a Gastric Ulcer
File:Benign gastric ulcer 1.jpg
 
    B - Gastric Cancer:  
    Infection with Helicobacter pylori is the leading bacterial infection associated with the development of cancer in humans.
    In less than 1% of cases of gastritis will evolve to gastric carcinoma.
    This development comes after several decades and a sequence of transformations of the mucosa where a pre-cancerous condition can be observed.
    The cancer mortality is still the second leading cause of cancer death in the world
 
 
    C - A cancer of the stomach:  

Lymphoma of MALT (Mucosa Associated Lymphoid Tissue) even rarer was his prognosis changed since the knowledge of Helicobacter pylori.  




    D - Other diseases or associated diseases:
    Infection with Helicobacter pylori has been implicated in other diseases or idiopathic syndromes, with varying levels of evidence.
    It has been reported by studies, the existence of anemia by decreasing the concentration of serum ferritin during infection by Helicobacter pylori.
    (These studies are contradictory, however, and are given here as a principle of precaution and care possible). 
 
 
Ulcerative colitis?

    E - In children:  
    Helicobacter pylori can cause gastric ulcers and duodenal ulcers, although most infections are asymptomatic.
    The recurrence of these diseases in children may be reduced by a proper eradication of Helicobacter pylori.
    The likelihood of Helicobacter pylori infection is higher among children from developing countries, than among children from industrialized countries.
 
 
 

Disease ulcerative



6 - TRANSMISSION ?

    They are mostly original or oral-fecal-oral, as Helicobacter pylori was found in saliva, dental plaque, and the stomach samples of fecal origin.  
    Other mechanisms are described: consumption of raw vegetables irrigated with sewage or poorly treated.     

7 - BACTERIOLOGICAL STUDY  

    A - Morphological Characteristics  
        Helicobacter pylori is:  
  • a small bacillus 0.5 m in diameter and 2 to 6 m in length 
  • slightly curved and medicine. 
  • Gram (-)
  • mobile with multiple flagella (referred to as 4 to 6 flagella) surrounded by a sheath and arranged according
  • to a ciliature péritriche. 
  • No-sporulated
   
    B - Characteristics cropping
    Its micro bacteria Aérophile (i.e. it requires oxygen), but is unable to grow an aerobically.
    Culture, however, requires 10% CO2
    The isolation and culture are on selective media such as:
  
• selective agar Helicobacter pylori (PYL) from Bio Mérieux)  
• Columbia agar / Brucella Chalgren Wilkins, enriched with 10% horse blood or sheep blood

    The boxes were incubated for 2 to 5 days at 98.6°F in   an atmosphere of micro Aérophile (10% CO)
    The presence of colonies is usually done by the appearance of translucent colonies, non-pigmented and a diameter of 1 mm.
 
    C - Character biochemical and enzymatic
    • catalase (+) 
    • oxidize (+ )
    • nitrate reductase (+ )
    • Urease + + + + 
    • The sugars are fermented
    • resistant to céfalotine 
    • sensitive to nalidixic acid 

8 - CRITERIA HELICOBACTER PYLORI ISOLATION

    This search for the presence of Helicobacter pylori should be systematic in people at high risk such as: 
• patients with a proven ulcer  
• patients with a partial gastrectomy for cancer  
• the parents of first-degree relatives of patients with gastric cancer  
• patients with pre-neoplastic lesions (atrophic gastritis ...)  
• patients with lymphoma of MALT (Mucosa Associated Lymphoid Tissue), rare tumor may regress after Helicobacter pylori treatment.
 
“H. pylori” bacteria.

9 - THE DIAGNOSTIC APPROACH  

    The main methods of helicobacter pylori diagnostic are:  
    A - Direct diagnosis:  
    It is made from samples taken by biopsy and placed in culture.
    Crops can be made basis of gastric biopsies and used to test the sensitivity or resistance to antibiotics.
    Resistance tests are indicated after the failure of anti-invectives.
    The taking of biopsies is mainly in the antrum and fundus and in an endoscopy (e.g. for a patient who reacts just treatment).
    It is then possible to perform culture and susceptibility testing to verify the sensitivity to treatment.

 
        A1 - A review of biopsies by Warthin Starry staining (staining method of silver impregnation), or Gram revealed curved bacteria on the surface of the epithelium of the mucosa and occasionally in the cytoplasm of cells.
        A2 - the second biopsy allows the realization of cultures in the laboratory.  
        A3 - the third biopsy allows the achievement of a rapid test to urea (urea-indole medium) by a simple turn of a pH indicator after 24 h incubation at 98.6°F.
    This rapid test is based on the production of urease by Helicobacter pylori.
    Gastric biopsy is placed in a medium containing urea.
    The activity of urease and the production of ammonium associated because a change in pH may be identified by an appropriate indicator.
 
Endoscopy Diagnosis and Biopsy
 
AV Number: AV-8000-0285
 
 

B - Indirect diagnosis:  
     It is based on serology, which is useful in screening but still restricted to specialized laboratories.
    Serology has an undeniable interest in the search for the presence of antigen-specific Helicobacter pylori in stool.
    It remains positive in most cases for many months after eradication of Helicobacter pylori.
    There are several serological techniques:  
        1 - This is an ELISA (Premier Platinum HpSa Enzyme Immunoassay Meridian Diagnostics Inc., Cincinnati, Ohio).
    The ELISA is currently the most reliable among the serological tests.
    It gives a qualitative answer.
    In subjects whose infection was proved by fibroscopy / biopsy, the antigen immunoassay revealed: 
• a sensitivity of 96%,  
• a specificity of 93% and  In fact, its sensitivity and specificity vary kits marketed.
    The limitations of the method are:
• IgM is not detected  
• The IgG appears only 3 weeks after the onset of illness  
• the presence of IgA can sometimes be detected in the absence of IgG

        Reminder:

    Should be used as samples of fresh feces.
    Until analysis, the stool should be stored up for 72 hours in a sealed container at a temperature of two to 8oC.
    The stool can be frozen and sent to the laboratory if the above conditions can be achieved.
    2 - Immunoblotting or Western Blot and another technique that is rarely used outside of specialized laboratories.
    Two kits are marketed: Helico-Blot ® 2 (Genelabs Diagnostics) and Bionobis ® that allow accurate diagnosis in the "bad areas" of the ELISA.
    This technique allows defining serum antibody profiles with:  
• the presence of anti-Cag A. 



10 - ANTIBIOTIC SUSCEPTIBILITY AND  

     There is resistance to:  
    • metronidazole in almost 10% of strains  
    • the same for clarithromycin 10%.  
    • to azithromycin (cross-resistance with clarithromycin)  
    • macrolide  
    • to imidazoles 

11 - THERAPEUTIC STRATEGY

    Treatment of Helicobacter pylori eradication is difficult and the use of several drugs in combination.  
Generally uses two antibiotics and acid secretion inhibitors (inhibitor of the proton pump IPP), the most used and omeprazole.


    The antibiotics most commonly used are  :
    • amoxicillin  
    • clarithromycin  
    • the metronidazole  
    • Tetracycline’s 

    Other antibiotics can be used, but still second-line such as:
 
    • Levofloxacin  
    • rifabutin  

    The usual duration of treatment is between one to two weeks, depending on the study protocol.
 
    There are several combinations (after execution of an antibiogram) and they are only indicative:
 
    The Clarithromycin in combination with omeprazole, eradication reduces to 78% 
    
    • amoxicillin       + clarithromycin  + omeprazole  
    • Amoxicillin       + Metronidazole  + Omeprazole  
    • Tetracycline     + Metronidazole  + Omeprazole  
    • metronidazole  + clarithromycin  + omeprazole 

    The association amoxicillin + metronidazole + clarithromycin and anti secretory partner, leads to ulcer healing and eradication of Helicobacter pylori 

    The levofloxacin and rifabutin when they are associated with amoxicillin would also efficient and should not be used as a second intention.
    Monitoring the effectiveness of the treatment is carried out by a breath test urea marked, 4 to 5 weeks after stopping treatment.

 

12 - SCREENING AND ERADICATION 

    The group of French Studies of Helicobacter (GEFH) recommended screening for Helicobacter pylori and eradication in all infected persons to prevent the occurrence of gastric cancer.  

 
    The major indications for eradication are:  
  • gastric ulcer disease and duodenal  
  • gastric lymphoma of MALT  
  • precancerous lesions of the stomach  
  • children  

    The prophylactic eradication referred for gastric carcinoma is currently under discussion.
 

13 - ANNEXES  

    A - Other culture media for helicobacter pylori

  • CVA:
                - Agar with sheep blood containing 20 mg /L
                - of cefoperazone, 10 mg /L
                - vancomycin and 2 mg /L
                - of amphotericin B. 
  • TVP:
                - Agar with sheep blood containing 5 mg /L
                - trimethoprim, 10 mg /L
                - vancomycin and 2500 IU /L
                - polymyxin B. 
    B - The main inhibitors of proton pump

 
  • Esomeprazole  
Nexium
    • Lansoprazole  
    • Omeprazole  
    • Pantoprazole  
    • Rabeprazole 
 
    Stomach Lining Protection
 
    • Bismuth salicylate
 
    H2 Blockers
 
    • Cimetidine
    • ranitidine
    • famotidine
 
 
 
 

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    UBIT 100 mg film-coated tablet, a drug intended for in vivo diagnosis of gastro duodenal infection by Helicobacter pyloriUrée 13C: medicine for diagnostic breath test urea.  

Timeline of peptic ulcer disease and Helicobacter pylori

Inflammatiry Bowel Disease tutorial

    Click the link for more information:
 

National Digestive Diseases Information Clearinghouse

2 Information Way
Bethesda, MD 20892–3570
Phone: 1–800–891–5389
TTY: 1–866–569–1162
Fax: 703–738–4929
Email: nddic@info.niddk.nih.gov
Internet: www.digestive.niddk.nih.gov


The Helicobacter Foundation
was founded by Prof Barry Marshal
http://www.helico.com/disease_duo.html


From 
Ondek - biologic delivery systems

Genetic modifications of the stomach bacteria to create vaccines

American Gastroenterological Association - Advancing the Science and Practice of Gastroenterology

European Helicobacter Study Group




CDC : Division of Bacterial Diseases (DBD)

- This site is for archive purposes only -


Helicobacter pylori 
and Peptic Ulcer Disease

Cartoon of healthy, smiling  people

A peptic ulcer is a sore or hole in the lining of the stomach or duodenum (the first part of the small intestine). People of any age can get an ulcer and women are affected just as often as men. Over 25 million Americans will suffer from an ulcer at some point during their lifetime. The good news is that most ulcers are caused by an infection with the bacterium, Helicobacter pylori , and can be cured in about two weeks with antibiotics.

Ulcer Facts



•  Most ulcers are caused by an infection, not spicy food, acid or stress.
•  The most common ulcer symptom is burning pain in the stomach.
•  Your doctor can test you for H. pylori infection.
•  Antibiotics are the new cure for ulcers.
•  Eliminating H. pylori infections with antibiotics means that your ulcer can be cured for good.


 

1-888-My Ulcer
For more information about H. pyloriinfection and ulcers, see your health care provider or call toll-free:
1-888-MY-ULCER. 
Para obtener más información sobre las infecciones causadas por H. pylori y las úlceras, consulte a su médico o llame gratis al 1-888-698-5237
Page Last Modified: September 23, 2005






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