Better Detection and Treatment Needed for H pylori Infections in Children

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The most important contributor to <i>H pylori</i> treatment failure is the continued problem of antibiotic resistance, particularly to clarithromycin.<i>Credit: Medical Images RM/Scott Bodell.</i>
The most important contributor to H pylori treatment failure is the continued problem of antibiotic resistance, particularly to clarithromycin.Credit: Medical Images RM/Scott Bodell.

According to Stanford T. Shulman, MD, Professor of Pediatric Infectious Disease at Northwestern University Feinberg School of Medicine, Chicago, and an Infectious Disease Advisor Editorial Board member, Helicobacter pylori infections rarely come to the attention of infectious disease specialists, who are often referred to for the later manifestations in adults. “Helicobacter infections almost never involve the pediatric infectious disease community clinically, as they are managed exclusively by [gastroenterologists],” Dr Shulman explained to Infectious Disease Advisor, pointing to the dearth of information available in the Red Book of infectious disease. “It's 1100 pages and there are exactly 2 pages on H pylori infections,” he observed.

The Red Book states that H pylori is a gram-negative, spiral, curved, or U-shaped bacillus believed to be transmitted via the fecal-oral, gastro-oral, or oral-oral routes from infected humans.1 Infections are common in children, occurring most frequently in the first 5 years of life.1

 

Prevalence and Transmission

Estimated prevalence of H pylori may be as high as 80% in underdeveloped nations, although it has decreased significantly worldwide as a result of improvements in hygiene and better environmental conditions.2 It is most concentrated in lower socioeconomic regions where overcrowding is common. A 2013 study by Mana et al3 found a 3.2% prevalence of H pylori infection among native-born Belgian children compared with a prevalence as high as 60% among children born to foreign parents.

“In developing countries such as in Latin America, the prevalence can be up to 20% of young children, whereas in developed countries like Germany, prevalence is much lower — about 2%,” Maria Greene, MD, an attending gastroenterologist at the Lurie Children's Hospital in Chicago told Infectious Disease Advisor. “In my practice, I see H pylori frequently as the cause of postprandial vomiting or upper abdominal pain in young children.”

A 2014 review by Iwańczak and Francavailla2 reported a higher prevalence among children in childcare in a meta-analysis,4 whereas a study from Japan5 reported a higher rate in multigeneration households where both mother-to-child and grandmother-to-child transmission increased prevalence, although the presence of infection in the father or grandfather did not affect prevalence.

Clinical Signs and Implications

Symptoms of H pylori in children are often mild and unspecific, contrary to in adults, who are likely to experience significant gastric pain and distress from gastritis and peptic ulcers. In recent years, a link between childhood H pylori and gastric cancer in adulthood has elevated the need to detect and treat H pylori in asymptomatic children.2

Additional pathogenic mechanisms have identified associations with iron-deficiency anemia, reported in a number of studies.6-10Helicobacter pylori gastritis can be a cause [for being] refractory to therapy for iron-deficiency anemia,” Dr Greene stated. “If endoscopic evaluation for [iron-deficiency anemia] is indicated, then testing for H pylori should be done. However, currently there is no recommendation to use breath test or stool H pylori antigen to screen for H pylori in those patients.”

Although a number of studies have indicated an influence of H pylori on growth hormones, and the Red Book reports that it is associated with “short stature,” this remains an area of controversy.1,2 No studies to date have proven conclusive, and this finding may be a coincidence of poor environment, where socioeconomic factors are more to blame.

Evidence for a link with asthma has proven weak,11 and a study by Karimi et al12 concluded that there was no significant association. Likewise, current knowledge indicates that H pylori most likely does not play a role in either thyroid disease or diabetes, as has been suggested.2,13 “There is no evidence in pediatrics about a link between diabetes type 1 or autoimmune thyroid disease. However, in adults, H pylori infection is thought [to be] a potential trigger of gastric autoimmunity and in particular autoimmune gastritis,” Dr Greene said.

Diagnosis

A 2017 annual review in Helicobacter reported that upper digestive endoscopy and biopsy remain the primary diagnostic tools in children, and that pathognomonic endoscopy may find nodular gastritis.13

Diagnosing H pylori in children presents additional challenges, however. “H pylori serology is not reliable in children,” Dr Greene noted. “We recommend H pylori breath test, which can be easily done in our gastroenterology clinic in children old enough to blow into a bag and drink a solution that tastes like lemonade or [have a] stool test for H pylori [antigen]. If there is failure to eradicate after 2 courses of different therapeutic regimens, we can perform an upper endoscopy with gastric biopsies, which are sent out for culture and sensitivities of the bacteria. Those results are very helpful to determine the types of antibiotics that will be effective. During endoscopy, if there is suspicion for H pylori, we perform a quick test of a stomach biopsy which confirms the presence of bacteria in the stomach (Campylobacter-like organism test).”

Treatment

Eradication is often difficult to achieve, requiring systematic treatments adjusted according to susceptibility profile and at least 90% treatment adherence. Eradication is confirmed with a breath test administered 6 weeks after completion of therapy.

Dr Greene explained that, “first-line therapy is the same as in adults, but of course in children, the dose of proton pump inhibitors (PPIs) and antibiotics is calculated based on body weight of the patient. Younger children may need a higher PPI dose per kg body weight compared with adolescents and adults to obtain sufficient acid suppression. Certain antibiotics such as tetracycline or levofloxacin, which can be used in adults, are not typically used in children less than 8 years of age. Tetracycline can cause permanent tooth discoloration or enamel hypoplasia in children during tooth development. Fluoroquinolones are associated with disabling and potentially irreversible serious adverse reactions.”

The most important contributor to H pylori treatment failure, however, is the continued problem of antibiotic resistance, particularly to clarithromycin.13 For this reason, Dr Greene said, “Sequential therapy is no longer recommended in adults or children due to exposure to 3 different antibiotics at once.” 

References

  1. Kimberlin DW, Long SS, Brady MT, Jackson MA, eds. Red Book 2015: Report of the Committee on Infectious Diseases 30th edition. Elk Grove Village, IL: American Academy of Pediatrics; 2015:379-381.
  2. Iwańczak B, Francavailla R. Helicobacter pylori infection in pediatrics. Helicobacter. 2014;19:46-51.
  3. Mana F, Vandebosch S, Miendje Deyi V, Haentjens P, Urbain D. Prevalence of and risk factors for H. pylori infection in healthy children and young adults in Belgium anno 2010/2011. Acta Gastroenterol Belg. 2013;76(4):381-385.
  4. Bastos J, Carreira H, La Vecchia C, Lunet N. Childcare attendance and Helicobacter pylori infection: systematic review and meta-analysis. Eur J Cancer Prev. 2013;22(4):311-319.
  5. Urita Y, Watanabe T, Kawagoe N, et al. Role of infected grandmothers in transmission of Helicobacter pylori to children in a Japanese rural town. J Paediatr Child Health. 2013;49(5):394-398.
  6. Harris PR, Serrano CA, Villagrán A, et al. Helicobacter pylori-associated hypochlorhydria in children, and development of iron deficiency. J Clin Pathol. 2013;66(4):343-347.
  7. Soundaravally R, Pukazhvandthen P, Zachariah B, Hamide A. Plasma ferritin and indices of oxidative stress in Helicobacter pylori infection among schoolchildren. J Pediatr Gastroenterol Nutr. 2013;56(5):519-522.
  8. Queiroz DMM, Harris PR, Sanderson IR, et al. Iron status and Helicobacter pylori infection in symptomatic children: an international multi-centered study. PLoS ONE. 2013;8(7):e68833.
  9. Ozkasap S, Yarali N, Isik P, Bay A, Kara A, Tunc B. The role of prohepcidin in anemia due to Helicobacter pylori infection. Pediatr Hematol Oncol. 2013;30(5):425-431.
  10. Azab SF, Esh AM. Serum hepcidin levels in Helicobacter pylori-infected children with iron-deficiency anemia: a case-control-study. Ann Hematol. 2013;92(11):1477-1483.
  11. Wang Q, Yu C, Sun Y. The association between asthma and Helicobacter pylori: a meta-analysis. Helicobacter. 2013;18(1):41-53.
  12. Karimi A, Fakhimi-Derakhshan K, Imanzadeh F, Rezaei M, Cavoshzadeh Z, Maham S. Helicobacter pylori infection and pediatric asthma. Iran J Microbiol. 2013;5(2):132-135.
  13. Kalach N, Bontems P, Raymond J. Helicobacter pylori infection in children. Helicobacter. 2017;22(S 1):e12414.

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