diagnosis and treatment of H pylori related diseases in children and adolescent

- Introduction

Helicobacter pylori (H. pylori) is one of the most common bacterial infections worldwide. ⁽¹⁾ It is a Gram-negative microaerophilic bacterium colonizes the gastric mucosa, ⁽²⁾ the infections are usually acquired during early childhood and generally passes asymptomatically in most patients, in which it will remain in the gastric cavity throughout life in the absence of eradication therapy. ⁽³⁾

The prevalence of infection in pediatric age is high and varies from country to country.  In Egypt, a population-based cross-sectional study performed among asymptomatic school children used urea breath test (UBT) to show that the overall H. pylori prevalence was 72.38%. Its main risk factor is residing in an overcrowded home and socially deprived area ⁽⁴⁾ In a rural area, relatives with low socioeconomic level generally showed the highest seroprevalence (82.5% and 78.1%, respectively). ⁽⁵⁾

Another cross-sectional study showed that seroprevalence of H. pylori was significantly age-dependent: 60.6% of patients aged more than 5 years and 25.9% of patients aged less than 5 years. One of the main factors associated with seroprevalence was crowding in beds. The seroprevalence among children was 59.7% in the case of more than 3 persons sharing a bed and 26.9% in the case of fewer than 3 persons sharing a bed.

Moreover, the duration of breastfeeding also played a role in H. pylori acquisition. The seroprevalence was 64.7% among children who were breastfed for <1 year and only 42.4% among those breastfed for more than 1 year. ⁽⁶⁾ A cross-sectional study showed prevalence of about 70%, indicating that the burden of H. pylori infection is high in rural areas than in urban areas. ⁽⁷⁾

Several diagnostic tests for detection of H. pylori have been widely used in clinical practice  either invasive which require endoscopy to obtain biopsies of gastric tissues,  or non-invasive methods with different levels of sensitivity and specificity.⁽⁸⁾ However, each of these tests has certain disadvantages ⁽⁹⁾ The invasive methods include histological examination, culture, urease test and molecular methods, while the non-invasive methods include urea breath testing, serology and stool antigen testing. There is no single method that can meet, on its own, the criteria for acceptable sensitivity and specificity in identification of the bacterium. In the last few years, more interest has been paid for the non-invasive methods. ⁽¹⁰⁾ Molecular testing assays can be also a rapid and accurate methods for the diagnosis of H. pylori infection. ⁽¹¹⁾

Spontaneous eradication is described mainly in infants and young children but unfortunately the eradication decreases with age. Without a treatment scheme, eradication is highly improbable. ⁽¹²⁾

Although H. pylori infection is mainly acquired in childhood, complications generally arise much later. H. pylori infection is implicated in the pathogenesis of gastritis, gastric and duodenal ulcers, gastric cancer, and gastric mucosa‑associated lymphoid tissue (MALT) lymphoma ^{(13- 16)} In 2018, H. pylori was responsible for an estimated 810,000 new cases of non-cardia gastric adenocarcinoma worldwide, making it the leading cause of infection-attributable cancer ahead of high-risk human papillomavirus and hepatitis B and C viruses. ⁽¹⁷⁾

 It is now established that chronic H. pylori infection is the most important etiological factor for the occurrence of gastric cancer, ^(18-21) which is considered as the third leading cause of cancer death globally. ⁽²²⁾ Importantly, its eradication is recommended in the treatment and/or prevention of these conditions.

There is a strong association between H. pylori infection and diseases like; lymphoma, cardiovascular disease, dermatological disease, liver and gallbladder diseases, anemia, diabetes mellitus, autoimmune disease, atopy, asthma, neurological disease, bone disease, micronutrient deficiency , iron deficiency anemia, growth restriction, and idiopathic thrombocytopenic purpura (ITP) ^(1,2,23) H. pylori infection can lead to these diseases apart from the gastro-intestinal system by a series of hormonal, immunological, cytokine and chemokine mediators.

Indications for treatment of this infection and optimal regimens have been proposed by a recent consensus guideline as well as optimal diagnostic tests. Eradication therapy should be considered in children under 5 years in whom the therapy is clinically indicated due to the disease or condition requiring a workup that results in the diagnosis of H. pylori infection including peptic ulcer diseases with stenotic lesion, perforation or recurrent hemorrhage, or MALT (mucosa‐associated lymphoid tissue lymphoma). Eradication therapy should also be considered in children who have recurrent or refractory IDA to iron supplementation and in whom an active H. pylori infection has been determined.

 All treatment guidelines agree that the best approach to the treatment of H. pylori infection is to succeed on the first attempt, thereby avoiding re-treatment and reducing cost, anxiety, and the further promotion of resistant strains. ⁽²⁴⁾

Treatment to eliminate H pylori infection is not expected to improve symptoms in children, except in cases of peptic ulcer disease (Gastric and duodenal ulcers) (PUD). Therefore, in children fulfilling the Rome criteria for functional abdominal pain, diagnostic testing (noninvasive or invasive) for H pylori infection should not be undertaken. (25-30) In the absence of alarm signs or symptoms (persistent right upper or right lower quadrant pain, dysphagia, odynophagia, persistent vomiting, gastrointestinal blood loss, involuntary weight loss, deceleration of linear growth, delayed puberty, unexplained fever, and a family history of inflammatory bowel disease, celiac disease, or PUD), recent updated recommendations from the committee for ROME IV did not identify compelling evidence to support upper endoscopy as part of the diagnostic work up. ⁽³¹⁾

Treatments targeting H. pylori infection consist of combinations of a PPI and several antimicrobial agents. ^(32,33) There are limited well-designed studies in children and adolescents with respect to the optimal duration of anti H pylori therapy. Meta-analyses of optimal duration of H pylori eradication therapy in adults have been performed and show that increasing the duration of therapy enhances eradication rates .⁽³⁴⁾ With respect to triple therapy, a recent systematic review and network analysis of studies in adults showed that 14-day duration of treatment improves eradication rates compared to 10-day, and both are superior to 7-day treatment. ⁽³⁵⁾

 The recommended goal for H pylori treatment is an eradication rate of at least 90% to avoid further investigations and antibiotic use. However, the latest clinical studies published have shown that the target of 90% eradication with first-line treatment may not be achieved by these regimens especially if treatment is not tailored to antimicrobial susceptibility tests and if compliance is not optimal (> 90%). ⁽³⁶⁾

This guideline was implemented for optimal diagnosis and treatment of H pylori related diseases in Egyptian children.