Helicobacter pylori infection causes gastritis and duodenal ulcers, and—to a lesser extent—gastric ulcers, and it is strongly associated with adenocarcinoma and mucosal-associated lymphomas in humans (1). Whereas seroepidemiological studies have identified childhood as an important period for acquisition of the infection, it is believed that persistent colonization, particularly that which results in overt clinical disease, is rare in the first year of life (2,3). We report 2 cases of symptomatic H pylori infection diagnosed by histology in 6-week-old and 4-month-old infants in the United States. As far as we are aware, these are the first reports of cases in such young infants.
CASE REPORT 1
A 2-month-old white infant boy was referred for the management of an upper gastrointestinal disorder. Symptoms consisted of frequent regurgitation, vomiting, gagging, back arching, and irritability. Adequate growth had occurred since birth. The infant was initially treated with ranitidine and metoclopramide. Subsequently, the ranitidine dose was increased, the metoclopramide was discontinued, and cereal added to the formula.
During the next 2 months, there was no clinical improvement, although a proton pump inhibitor was started and formula was changed to a hydrolysate formula. The patient demonstrated poor weight gain and continued to be irritable. An upper endoscopy when he was 4 months old showed visibly normal-appearing mucosa of his esophagus, stomach, and duodenum. Microscopic examination of biopsy specimens obtained showed normal esophageal histologic appearance. However, chronic inactive gastritis was observed, with increased plasma cells in the lamina propria, regenerative changes of the mucosa, and H pylori–like organisms identified with Diff-Quick staining. The patient received triple therapy with clarithromycin, amoxicillin, and lansoprazole for 2 weeks. At follow-up 6 weeks later, the patient had complete resolution of symptoms. The proton pump inhibitor was discontinued 3 months after the completion of eradication therapy. No further testing for H pylori was done at the time of this writing, but testing is planned in the near future. Test results of the patient's parents for H pylori by stool antigen testing were negative; however, test results of the maternal grandfather, uncle, and cousin by the same method were positive.
CASE REPORT 2
A 6-week-old African American infant boy was transferred for evaluation of feeding aversion and irritability during feeds. At birth, he experienced respiratory distress and required continuous positive airway pressure support for the first 2 days of life. Enteral feeds via nasogastric tube were initiated at the second day of life and oral feeds during the second week of life. The infant did not feed well, taking formula from a bottle poorly. Ranitidine and metoclopramide were started empirically, then a change was made to proton pump inhibitor therapy, without additional improvement in symptoms. Further diagnostic evaluation included magnetic resonance imaging of the brain, thyroid studies, and determination of serum amino acids and urine organic acids; all of the results were normal. The patient seemed hungry but took only small amounts of oral feeds. Speech-language pathology and videofluoroscopic evaluation of his oral pharyngeal function showed no abnormalities. A 24-hour pH probe study revealed significantly abnormal acidification of the esophagus with reflux index of 24.5%. An upper endoscopy showed mild duodenitis and no esophagitis. However, H pylori-like organisms were identified by Diff-Quick staining on histology, along with focal active gastritis characterized by increased plasma cells in the lamina propria and regenerative changes of the gastric mucosa. The patient was treated with amoxicillin, metronidazole, and lansoprazole for a total of 2 weeks. At the time of discharge 4 days later, his gastrointestinal symptoms had improved, but he was still receiving most of his feeds through a nasogastric tube. At follow-up, he continued to experience feeding aversion, prompting repeat endoscopic and histological examinations, whose results were normal with demonstration of successful eradication. A percutaneous gastrostomy placement was performed when he was 5 months old to provide additional nutrition support. The mother of the infant was tested for antibodies to H pylori by serology; the results were negative. No other family members were available for testing.
We report the youngest cases, to our knowledge, of definitive and symptomatic H pylori infection described to date in the United States; specifically, in infants 6 weeks old and 4 months old. There are few case reports in the literature of documented H pylori infection in infants younger than 6 months of age (4–7). The demographics and clinical characteristics of the previously reported infants with diagnoses of H pylori infection in comparison with our 2 cases are summarized in Table 1.
In this report, we observed clinically significant H pylori infection occurring much earlier in life than was originally believed (2). Previously published epidemiological studies showed that H pylori infection is rare in infants (2). However, these study findings were based on the use of noninvasive diagnostic tests such as serology and the urea breath test, which have lower sensitivity and specificity in very young children (2,3). The current gold standard for the diagnosis of pediatric H pylori infection in North America is by endoscopy with gastric biopsy, which uses primary culture, or the identification of organisms by histological staining and urease testing (8). Our cases were both diagnosed by histology demonstrating established infection resulting in clinically evident symptoms. In 4 of 5 infants previously reported in the literature (Table 1), the diagnosis was also made by histology; 1 case was identified by culture.
The route of transmission of H pylori remains incompletely defined. Infection is thought to result from direct human-to-human contact via fecal–oral, oral–oral, or gastro–oral routes (1). Contaminated water has also been shown to be a reservoir. Low socioeconomic condition is an associated risk factor, and transmission is believed to occur as a result of crowded conditions. Test results for H pylori were negative in the primary caregivers of both our patients but positive in the grandfather, the uncle, and the cousin of the 4-month-old, who were living in the same household. As shown in Table 1, parents were infected in only 2 (25%) of the 8 reported infants, and poor socioeconomic status identified in 4 (50%). These data do not support a definitive conclusion regarding the route of transmission.
Recurrent vomiting was observed in our first case and in 4 of the 6 infants reported in the literature. This clinical feature is consistent with other investigators who observed profuse vomiting in the absence of diarrhea as a consistent feature of acute infection with H pylori (9). Vomiting is not unusual in this age group, however, which makes it difficult to differentiate gastroesophageal reflux from emesis due to other causes such as acute H pylori infection (10). The severity of symptoms and the failure to respond to standard reflux therapy triggered further investigation in both our cases and in the other reports in the literature (4). Although the 6-week-old infant did not manifest specific regurgitation reflux-related symptoms, he did have severe gastrointestinal reflux, as demonstrated by the 24-h pH monitoring. Whether H pylori infection contributed to the severity of his gastroesophageal reflux or was merely a coexisting condition remains unclear.
Histologically proven but not endoscopically evident gastritis was present in our cases as well as in the majority of the other reported cases (4–7). Histological evidence of gastritis is observed in the majority of H pylori-infected patients and in most cases does not correlate with endoscopic findings (8,11). This lack of correlation between endoscopic findings and histological findings is a consistent observation in the practice of pediatric gastroenterology and merits biopsy as the standard practice when endoscopy is performed (12).
The natural history of H pylori infection in infancy after acquisition and successful colonization remains unknown. Studies in areas where H pylori infection is endemic have suggested that some children infected at an early age may even lose the infection upon follow-up and other children remain infected and experience severe disease (3,13,14). Although these studies implied that infection can be transient, the validation, accuracy, and predictive value of the noninvasive tests used in the infants enrolled in these studies limit their findings (3,14). Further studies that use well-validated and noninvasive detection methods are sorely needed. An asymptomatic infant in the cases reported in the literature was not treated, and the infection “spontaneously” resolved, as evidenced by negative results in histology specimens obtained during a repeat upper endoscopy (6). Because the symptoms in our cases were clinically significant, we chose to treat both infants. The symptoms of the 4-month-old improved with therapy, but improvement cannot be ascertained for the 6-week-old, whose feeding aversion may not be caused by H pylori infection. Owing to a lack of published randomized controlled treatment trials in children infected with H pylori, there is no compelling evidence that supports treatment of histologically proven H pylori gastritis in the absence of peptic ulcer disease (15). The guidelines suggest that the decision is left to the discretion of the clinician and the family (1).
We describe the youngest cases, as far as we are aware, of definitive symptomatic H pylori infection reported in the United States. H pylori infection seemed to account for the symptoms of the 4-month-old infant and, we speculate, contributed to the severity of gastroesophageal reflux in the 6-week-old infant. Intractable vomiting seems to be a consistent feature of these infected infants and may indicate H pylori infection as a possible cause. However, infection with H pylori in this age group in the United States is relatively infrequent. Thus, clinicians should consider other conditions that commonly affect the upper gastrointestinal tract of infants before making any evaluation of H pylori infection in this age group. During endoscopic evaluation, gastric biopsy should be performed because there is poor correlation between the endoscopic and microscopic features. Although epidemiological studies in developed countries suggest that H pylori infection seems to be rare in infants younger than 1 year of age, our report and the literature reviewed herein suggest that the infection can occur in infants younger than 6 months of age. Thus, awareness is important so that appropriate investigations can be made because a missed or delayed diagnosis can lead to unnecessary procedures and therapies as well as increased long-term morbidity caused by this gastric pathogen.
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