GI Infections - Helicobacter Pylori

Question 1

Describe the features of Helicobacter pylori

Answer 1

Spiral Gram negative rod but polymorphic
- in adverse conditions (it becomes coccoidal in shape)

It has one to five unipolar flagella, each with a membranous terminal bulb, is highly motile

Causes chronic diseases of the GI tract

Question 2

Describe the epidemiology of Helicobacter pylori

Answer 2

H.pylori is uncommon in young children

In developing countries:-
- Most adults are infected
- Most children are infected by their teens
Acquisition occurs in about 10% of children per annum between the ages of 2 and 8 years so that most are infected by their teens
15 – 20% of infected develop severe GI disease

In developed countries:-
H.pylori affects about 20% of persons below the age of 40 years, and 50% of those above the age of 60 years. Low socio-economic status predicts H.pylori infection
Immigration is responsible for isolated areas of high prevalence in some Western countries

Question 3

How is H. Pylori transmitted?

Answer 3

Route is still not confirmed

Appears to be only one reservoir - human stomach

• person to person most likely route of infection
• faecal-oral route - cultured in faeces
• oral-oral route - found in dental plaque using PCR

Question 4

What are the virulence factors of H. pylori?

Answer 4

1) Urease converts urea (from saliva and gastric juices), into bicarbonate & ammonia, which are alkaline
- creates cloud of acid neutralising chemicals around H. pylori, protecting it from the acid in stomach
2) Motility - uses spiral shape and flagella
3) Vacuolating cytotoxin - produce acidified vacuoles leading to cell death - cell eventually dies - pool of nutrients
4) Adhesion pedestal - adhere to host cell
5) Resistance to Immune response - suppresses immune response and also partially resists killing by phagocytes
6) Phospholipase – mucus breakdown
7) Cag Pathogenicity Island:
- Type IV secretion system (made up of ~ 11 proteins evolved from conjugation apparatus)
- Cag A (cytotoxin-associated gene A) – increases acid production and alters cell division/apoptosis balance

Question 5

How does H. pylori infection present?

Answer 5

Because of strain and host variation H.pylori has various disease clinical presentations:
Gastritis
Non-ulcer dyspepsia
Stomach cancer
Duodenal & Gastric Ulcers
Non gastric diseases - coronary heart disease, skin rashes, chronic halitosis, sudden infant death syndrome

Question 6

Describe gastritis caused by H. pylori

Answer 6

All Hp infected patients develop chronic gastric inflammation (type B) but condition is usually asymptomatic

H.pylori colonises and infects the gastric mucosa

• chronic gastric inflammation (type B) –normally asymptomatic
• gastric mucosa infiltrated by mononuclear & polymorphonuclear leukocytes (WBC)

Intestinal metaplasia – gastric mucosa resembles intestine mucosa (atrophy)

Question 7

Describe non-ulcer dyspepsia associated with H. Pylori

Answer 7

25 % of population suffer
H. pylori present in 30-60% of patients

Recurrent abdominal pain or discomfort centred in upper abdomen, some may suffer nausea or chronic vomiting

Role of H. pylori in non-ulcer dyspepsia remains unclear, but many doctors treat with antibiotics if H. pylori present

Question 8

Describe the features of stomach cancer associated with H. pylori

Answer 8

Stomach cancer causes 750,000 deaths per year; 70-90% cases due to H.pylori infection
Most common in countries such as Colombia and China, where H. pylori infects over half the population in early childhood.
Classified as a type I carcinogen by the WHO

Long term tissue damage favours cell proliferation gives increase risk of malignant alterations
Intestinal atrophy occurs - precursor lesion to cancer

Other risk factors include low Vits C & E, calcium, high salt & smoking

Question 9

Describe the features of duodenal and stomach ulcers associated with H. pylori

Answer 9

Present in 70-100 % of patients

Gastritis is known to be the essential pre-requisite for peptic ulceration

Question 10

Describe the pathogenesis of duodenal and stomach ulcers associated with H. pylori

Answer 10

“Ulcer strain” produces vacuolating cytotoxin

Induces inflammation (neutrophils), apoptosis, atrophy

Breakdown in mucosal defences - acid attack of gastric or duodenal mucosa

Question 11

What are the symptoms of duodenal and stomach ulcers associated with H. pylori?

Answer 11

Burning pain in the epigastrium - when the stomach is empty, relieved by eating or by taking antacids.

Less common symptoms include: 
Nausea
Vomiting
Loss of appetite
Bleeding

Question 12

How is H. pylori infection treated?

Answer 12

Currently no therapy that is 100% effective for H.pylori infection

Successful therapies for H.pylori consist of 2 to 4 drugs given for periods of 7-14 days - must have efficacy of >80-90% in clinical trials.

Routine treatment of + ve asymptomatic patients NOT recommend Exceptions patients with :

• Relatives with gastric cancer,
• Infected spouses of a patient reinfected with H.pylori

Question 13

What are the problems with treating H. pylori infection?

Answer 13

Several barriers to antibiotic therapy:

	i) acidity of intestinal environment                                                                                              	
 		ii) inability of drugs to penetrate gastric mucus layer

Relies heavily on patient compliance

1/2 world’s population is infected - widespread treatment could cause resistance problems - already metronidazole & clarithromycin resistant strains

Undesirable side-effects can include diarrhoea, nausea & vomiting