REVIEW

Specific aspects of Helicobacter pylori infection in children

 Aspecte specifice ale infecţiei cu Helicobacter pylori la copii

First published: 30 iunie 2022

Editorial Group: MEDICHUB MEDIA

DOI: 10.26416/Pedi.66.2.2022.6615

Abstract

Helicobacter pylori infection is acquired in childhood and affects more than half of the world population. The majority of infected children are asymptomatic. The role of Helicobacter pylori infection in chronic abdominal pain of unclear etiology in children remains a controversial issue. Chronic Helicobacter pylori infection plays a pivotal role in the development of various gastric and extragastric diseases. The absence of its eradication therapy leads to prolonged exposure and to its carcinogenic potential. The diagnosis of infection should be based on upper-digestive endoscopy with biopsy-based methods. Eradication control after treatment should be based on validated noninvasive tests. The management of Helicobacter pylori infection in children remains a problem in clinical practice.

Keywords
Helicobacter pylori, children, endoscopic, treatment

Rezumat

Dobândirea infecţiei cu Helicobacter pylori este preoce în co­pi­lă­rie, afectând peste jumătate din populaţia lumii. Majoritatea in­fec­ţii­lor produse la copii sunt asimptomatice. Rolul infecţiei cu Heli­cobacter pylori în durerile abdominale cronice de etio­lo­gie neprecizată la copii rămâne o problemă extrem de con­tro­ver­sa­tă în prezent. Infecţia cronică cu Helicobacter pylori este incriminată în patogeneza unui spectru larg de afecţiuni gas­tri­ce digestive şi extradigestive. În absenţa unei terapii spe­ci­fice de eradicare, infecţia persistentă produce inflamaţie cro­ni­că, având potenţial rol evolutiv carcinogen. Endoscopia di­ges­ti­vă superioară asociată cu biopsie este considerată a fi cea mai fiabilă metodă de diagnosticare a infecţiei cu Helico­bac­ter pylori. Controlul eradicării acestei infecţii se poate realiza pe baza testelor diagnostice neinvazive. Manage­mentul infecţiei cu Helicobacter pylori la copii rămâne o problemă importantă în practica clinică pediatrică.

Introduction

Helicobacter pylori is a spiral Gram-negative microaerophilic bacterium that colonizes normal or ectopic gastric mucosa. Even though the prevalence of H. pylori has declined over the recent decades, due to the improved sanitation and socioeconomic development, this infection affects nearly 50% of the population worldwide, and its prevalence remains high in most countries(1). The prevalence is low (1.2-12.2%) in developed countries, but a very high prevalence (60-80%) has been reported in low- and middle-income countries(2).

The transmission of H. pylori is mainly oral-oral or oral-fecal. The contaminated water can also be a source of infection in which the bacterium can remain for long periods in a viable state.

Clinical manifestations

This infection is usually acquired in early childhood, with a median of 10 years old. The infection is associated with a varied clinical picture: chronic gastritis, peptic ulcer disease, in particular duodenal ulcer, non-ulcer dyspepsia, gastric atrophy, intestinal metaplasia, gastric adenocarcinoma and gastric mucosa associated lymphoid tissue (MALT) lymphoma. H. pylori infection is the main risk factor for gastric cancer; furthermore, H. pylori was classified by World Health Organization (WHO) as a first-class carcinogenic agent(3).

H. pylori infection has also been involved in the pathogenesis of extragastric disease, including: unexplained iron deficiency anemia, chronic immune thrombocytopenic purpura, chronic urticaria, vitamin B12 and acid folic deficiency, growth failure, short stature and development retardation. The extradigestive manifestations of H. pylori infection are determined mainly by cagA-positive strains.

The hypochlorhydria associated with H. pylori infection is a risk factor for the acquisition of other entero­pathogens and diarrheal disease(4). The bacterial infection affects the digestion and absorption of nutrients, such as vitamin B12, vitamin C, vitamin A, vitamin E, folate and selenium, by disrupting gastric secretion and acidification(5).

Several studies have shown that H. pylori affects the level of vitamin D receptor at the tissue and the cell levels, but this association remains unknown and still needs studies with larger samples(6).

A recent meta-analysis suggests that H. pylori may have immunoregulatory properties in inflammatory bowel disease and an increase association with Crohn’s disease in children(7,8).

H. pylori gastritis affect the production of ghrelin, a 28-amino-acid peptide that controls the appetite and satiety, contributing to the regulation of somatic growth and adipose tissue and plays a role in food intake, gastric motility and acid secretion(9,10).

Another meta-analysis showed that H. pylori infection has been associated with a reduce risk of asthma and allergy in children(11). It is demonstrated that there is an inverse correlation between H. pylori infection and the risk of esophageal adenocarcinoma. Future research is needed in this regard.

H. pylori infection is involved in the pathogenesis of diabetes mellitus and is correlated with elevated levels of C-reactive protein, IL6 and TNF-a, which are markers of inflammation involved in insulin resistance(10).

The infection causes a chronic inflammation of the gastric mucosa with an increased expression of toll-like receptors (TLRS) and cytokines (IL-8, IL-10, TNF-a) and an increased epithelial proliferation(12).

The development of the disease is related to the virulence of strain; it is well documented that genes such as cytoxin gene A (cag A) and vacuolating cytotoxin A (vac A) increase the risk of severe gastric disease(13). In contrast to the proinflammatory response found in adults, children tend to have lower levels of Th1 and Th17 related cytokines, and overexpression of IL-10 and of transforming growth factor b, resulting in a lower degree of polymorphonuclear cell activation in the acute phase of infection(14).

All the colonized patients develop gastritis, but 80% of the infected persons are asymptomatic and a small proportion of the infected subjects develop symptoms of gastric or extragastric disease. The clinical manifestations are nonspecific and recurrent abdominal pain represents the main symptom(15). Sykora et al. revealed in recent studies a positive correlation between H. pylori infection and functional abdominal pain disorders fulfilling the Rome criteria(16).

A meta-analysis intented to demonstrate a possible association between the infection and the symptoms concluded that it was not related to vomiting, diarrhea, flatulence, chronic functional abdominal pain, halitosis, regurgitation, constipation or nausea(17).

However, recent meta-analyses have documented a significant statistical association with epigastric pain(18). H. pylori infection may cause gastroduodenal ulcers, persistent vomiting, digestive bleeding, iron deficiency anemia and malnutrition, which are the main indications for the diagnostic testing for H. pylori infection.

Diagnosis

According to the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and to the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) guidelines, revised in 2016, H. pylori diagnosis require at least two invasive tests: a positive culture or a histopathologic finding of H. pylori gastritis, accompanied by urease rapid test(19).

The noninvasive assessment methods such as urea breath test and stool antigen are reserved to determine whether H. pylori has been eradicated. Antibodies for H. pylori remain for a time after eradication and the test does not allow to differentiate between a current and a past infection.

Several observational studies have revealed that there is no significant statistical association between chronic abdominal pain and H. pylori infection, therefore testing is not indicated in cases of abdominal pain in the absence of sign or symptoms suggestive for organic disorders(20). Testing for H. pylori should not be performed in children presenting with abdominal pain and/or dyspepsia suggestive for a functional disorder(19).

The initial diagnosis of H. pylori infection in children should be based on the findings of upper endoscopy, for instance antral nodularity, duodenal erosions or ulcer, in a child with gastrointestinal symptoms suggestive for an organic disease. The test and treatment strategy of H. pylori infection based on positive results of a noninvasive test are not indicated in children(19).

The use of polymerase chain reaction (PCR) techniques is an invasive test and can provide information on antimicrobial resistance.

Treatment

The treatment in children is controversial due to the prevalence of infection in a geographical area, the high rate of antimicrobial resistance, along with the presence of complications associated with H. pylori. The first-line treatment should be administered when the susceptibility profile is known. If the antimicrobial susceptibility is not known, the first-line treatment should not include clarithromycin, according with the recent studies which have shown that clarithromycin resistance is higher than 15%(19).

In case of first-line treatment failure or clarithromycin resistance, we can use triple therapy by replacing clarithromycin for metronidazole and vice versa. If the strain is resistant to either of those two drugs, we can administer the triple therapy with a high dose of amoxicillin or the quadruple therapy with bismuth, with the potential substitution of tetracycline for amoxicillin in children aged more than 8 years old(19). If the drug resis­tance profile is unknown, in case of first-line treatment failure it is recommended to do an additional endoscopic examination and perform a test for drug resistance.

Conclusions

The decision to diagnose and treat the Helicobacter pylori infection in children should be taken considering the clinical variability of digestive or extradigestive symptoms observed in clinical practice and the increase in the prevalence of antimicrobial resistance reported in the recent studies.  

 

Conflict of interests: The authors declare no con­flict of interests.

 

Bibliografie

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  7. Castaño-Rodríguez N, Kaakoush NO, Lee WS, Mitchell HM. Dual role of Helicobacter and Campylobacter species in IBD: a systematic review and meta-analysis. Gut. 2017;66(2):235-249. doi:10.1136/gutjnl-2015-310545.

  8. Wang WL, Xu XJ. Correlation between Helicobacter pylori infection and Crohn’s disease: a meta-analysis. Eur Rev Med Pharmacol Sci. 2019;23(23):10509-10516. doi:10.26355/eurrev_201912_19691.

  9. Boltin D, Niv Y. Ghrelin, Helicobacter pylori and body mass: is there an association?. Isr Med Assoc J. 2012;14(2):130-132.

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  11. Chen C, Xun P, Tsinovoi C, et al. Accumulated evidence on Helicobacter pylori infection and the risk of asthma: a meta-analysis. Ann Allergy Asthma Immunol. 2017;119:e2:137–45.

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