Anne J. Lagomarcino

Objectives: Helicobacter pylori (H. pylori) is the primary cause of gastric cancer and eradication in healthy adults has proven effective in decreasing cancer incidence. H. pylori is acquired largely in early childhood, however, the benefits of eradication in children are controversial. We aimed to determine the effect of H. pylori eradication on clinical and laboratory markers associated with gastric damage in apparently healthy school‐aged children.Methods: This was a pilot non‐blinded trial including 61 children persistently infected with H. pylori who were randomized to eradication/no treatment and followed for at least 12 months, evaluating clinical and blood markers (Pepsinogen I (PGI) and II (PGII) determined by ELISA) associated with gastric damage. The treatment consisted of a sequential scheme including 7 days of omeprazole + amoxicillin followed by 7 days of omeprazole + clarithromycin + metronidazole; adherence and tolerance were surveyed. Eradication rates were assessed by stool antigen detection or urea breath test 1 month following treatment every 4 months thereafter to detect reinfection.Results: Eradication occurred in 30/31 treated children (median age: 8.8, range: 7.9–10.8) and in 0/30 non‐treated controls (median age: 8.6, range: 7.9–11) (p < .001). Treatment was associated with mild transient symptoms (altered taste, nocturnal upper abdominal pain, nausea, and diarrhea). Baseline frequency of symptoms was low and eradication did not change symptoms compared to controls. PGI, PGII, and anti‐H. pylori seropositivity were similar in both groups at baseline and significantly decreased only in eradicated patients; PGI (92.5 vs. 74.4, p < .001), PGII (15.2 vs. 8.9, p < .001) levels, and frequency of anti‐H. pylori seropositivity (100 vs. 68%, p < .001) respectively. Four eradicated children (13%) were reinfected during follow‐up.Conclusions: H. pylori eradication therapy in apparently asymptomatic school‐aged children was well tolerated and associated with decreased serum PGI and PGII levels. Future studies should expand on the middle‐long‐term effect of early H. pylori eradication, especially on preventing gastric cancer.

Background: Healthcare workers (HCWs) are at increased risk for SARS-CoV-2 infection, however not all face the same risk. We aimed to determine antibody prevalence and risk factors associated with seropositivity in the Chilean HCW community. Methods: This was a nationwide, cross-sectional study consisting of a questionnaire and COVID-19 antibody testing. All HCWs in the Chilean public health care system were invited to participate three to four months following the peak of the country's first wave. Findings: Overall SARS-Cov-2 blood antibody positivity by fingerstick or venipuncture in 85 529 HCWs was 7 · 2%, ranging from 1 · 6% to 12 · 4% between regions. SARS-Cov-2 positive PCR results were self-reported in 8 330 individuals (9 · 7%) of which 47% were seropositive. Overall 10 863 (12 · 7%) either reported prior PCR positive results and/or were seropositive. Several factors were independently associated with higher IRR for seropositivity, including working in hospital (IRR 1·484), medicine/surgery w ards (IRR 1·383), emergency room (IRR 1·266), and night shifts (IRR 1·616), as were history of contact with a confirmed case (IRR 1·462), and use of public transport (IRR 1·367). These variables remained significant when including self-reported PCR positive cases in the model. Interpretation: HCWs in the hospital were at highest risk for COVID-19, especially if working in medicine/surgery wards or emergency rooms, in night shifts, older age, exposed to confirmed cases and/or using public transport. Antibody results using lateral flow likely underestimated true infection rates by nearly 40-50%. Nevertheless, risk factors were sustained when adjusting for self-reported PCR positive cases. Funding: No funding institution. Conflict of Interest: Authors do not declare any conflict of interest. Ethical Approval: The study was designed in August 2020 by Health Ministry personnel in conjunction with an academicadvisory board; the study was approved by the Ethical Committee of the Servicio de Salud Araucanía Sur (Nº CEC-201, August 10, 2021).

A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak affecting 52 people from a large school community in Santiago, Chile, was identified (12 March) 9 days after the first case in the country. We assessed the magnitude of the outbreak and the role students and staff played using self-administered antibody detection tests and a self-administered survey. The school was closed on 13 March, and the entire community was placed under quarantine. We implemented a home-delivery, self-administered, immunoglobin (Ig) G/IgM antibody test and survey to a classroom-stratified sample of students and all staff from 4–19 May. We aimed to determine the overall seroprevalence rates by age group, reported symptoms, and contact exposure, and to explore the dynamics of transmission. The antibody positivity rates were 9.9% (95% confidence interval [CI], 8.2–11.8) for 1009 students and 16.6% (95% CI, 12.1–21.9) for 235 staff. Among students, positivity was associated with a younger age (P = .01), a lower grade level (P = .05), prior real-time polymerase chain reaction (RT-PCR) positivity (P = .03), and a history of contact with a confirmed case (P < .001). Among staff, positivity was higher in teachers (P = .01) and in those previously RT-PCR positive (P < .001). Excluding RT-PCR–positive individuals, antibody positivity was associated with fever in adults and children (P = .02 and P = .002, respectively), abdominal pain in children (P = .001), and chest pain in adults (P = .02). Within antibody-positive individuals, 40% of students and 18% of staff reported no symptoms (P = .01). Teachers were more affected during the outbreak and younger children were at a higher risk for infection, likely because index case(s) were teachers and/or parents from the preschool. Self-administered antibody testing, supervised remotely, proved to be a suitable and rapid tool. Our study provides useful information for school reopenings.

Helicobacter pylori (H. pylori) is well-known to be involved in gastric carcinogenesis, associated with deregulation of cell proliferation and epigenetic changes in cancer-related genes. H. pylori infection is largely acquired during childhood, persisting long-term in about half of infected individuals, a subset of whom will go on to develop peptic ulcer disease and eventually gastric cancer, however, the sequence of events leading to disease is not completely understood. Knowledge on carcinogenesis and gastric damage-related biomarkers is abundant in adult populations, but scarce in children. We performed an extensive literature review focusing on gastric cancer related biomarkers identified in adult populations, which have been detected in children infected with H. pylori. Biomarkers were related to expression levels (RNA or protein) and/or methylation levels (DNA) in gastric tissue or blood of infected children as compared to non-infected controls. In this review, we identified 37 biomarkers of which 24 are over expressed, three are under expressed, and ten genes are significantly hypermethylated in H. pylori-infected children compared to healthy controls in at least 1 study. Only four of these biomarkers (pepsinogen I, pepsinogen II, gastrin, and SLC5A8) have been studied in asymptomatically infected children. Importantly, 13 of these biomarkers (β-catenin, C-MYC, GATA-4, DAPK1, CXCL13, DC-SIGN, TIMP3, EGFR, GRIN2B, PIM2, SLC5A8, CDH1, and VCAM-1.) are consistently deregulated in infected children and in adults with gastric cancer. Future studies should be designed to determine the clinical significance of these changes in infection-associated biomarkers in children and their persistence over time. The effect of eradication therapy over these biomarkers in children if proven significant, could lead to modifications in treatment guidelines for younger populations, and eventually promote the development of preventive strategies, such as vaccination, in the near future.

Introduction: Long‐term persistent Helicobacter pylori infection has been associated with ulceropeptic disease and gastric cancer. Although H. pylori is predominantly acquired early in life, a clear understanding of infection dynamics during childhood has been obfuscated by the diversity of populations evaluated, study designs, and methods used.Aim: Update understanding of true prevalence of H. pylori infection during childhood, based on a critical analysis of the literature published in the past 5 years.Methods: Comprehensive review and meta‐analysis of original studies published from 2011 to 2016.Results: A MEDLINE^®/PubMed^® search on May 1, 2016, using the terms pylori and children, and subsequent exclusion, based on abstract review using predefined criteria, resulted in 261 citations. An Embase^® search with the same criteria added an additional 8 citations. In healthy children, meta‐analysis estimated an overall seroprevalence rate of 33% (95% CI: 27%‐38%). Seven healthy cohort studies using noninvasive direct detection methods showed infection prevalence estimates ranging from 20% to 50% in children ≤5 and 38% to 79% in children >5 years. The probability of infection persistence after a first positive sample ranged from 49% to 95%. Model estimates of cross‐sectional direct detection studies in asymptomatic children indicated a prevalence of 37% (95% CI: 30%‐44%). Seroprevalence, but not direct detection rates increased with age; both decreased with increasing income. The model estimate based on cross‐sectional studies in symptomatic children was 39% (95% CI: 35%‐43%).Conclusions: The prevalence of H. pylori infection varied widely in the studies included here; nevertheless, model estimates by detection type were similar, suggesting that overall, one‐third of children worldwide are or have been infected. The few cohort and longitudinal studies available show variability, but most studies, show infection rates over 30%. Rather surprisingly, overall infection prevalence in symptomatic children was only slightly higher, around 40%. Studies including only one positive stool sample should be interpreted with caution as spontaneous clearance can occur.

Background: Helicobacter pylori infects half of the world's population and causes gastric cancer in a subset of infected adults. Previous blood microarray findings showed that apparently healthy children, persistently infected with H. pylori have differential gene expression compared to age-matched, non-infected children. SLC5A8, a cancer suppressor gene with decreased expression among infected children, was chosen for further study based on bioinformatics analysis. Methods: A pilot study was conducted using specific qRT-PCR amplification of SLC5A8 in blood samples from H. pylori infected and non-infected children, followed by a larger, blinded, case-control study. We then analyzed gastric tissue from H. pylori infected and non-infected children undergoing endoscopy for clinical purposes. Results: Demographics, clinical findings and family history were similar between groups. SLC5A8 expression was decreased in infected versus non-infected children in blood, 0.12 (IQR: 0 – 0.89) versus 1.86 (IQR: 0 – 8.94, P=0.002), and in gastric tissue, 0.08 (IQR: 0.04 – 0.15) versus 1.88 (IQR: 0.55 – 2.56; P=0.001). Children who were both stool positive and seropositive for H. pylori had the lowest SLC5A8 expression levels. Conclusions: H. pylori infection is associated with suppression of SCL5A8, a cancer suppressor gene, in both blood and tissue samples from young children.

Background: We previously detected Helicobacter pylori infection by stool antigen ELISA assay in 33‐41% of asymptomatic Chilean children between 2–3 years of age, of which 11–20% had a transient infection and 21–22% a persistent infection. A total of 88% of ELISA‐positive samples were also rtPCR positive, while 37/133 (33%) of ELISA‐negative stool samples were rtPCR positive. The significance of a ELISA‐negative/rtPCR‐positive sample requires clarification. We aimed to determine whether rtPCR is able to detect persistent infections not detected by ELISA.Materials and Methods: We selected 36 children with an ELISA‐negative/rtPCR‐positive stool sample, of which 25 were never H. pylori infected according to ELISA, and 11 had a transient infection with an ELISA‐positive sample before or after the discordant sample. At least two additional consecutive ELISA‐negative samples per child were tested in duplicate by rtPCR for the 16s rRNA gene.Results: A total of 14 of 78 (17.9%) rtPCR reactions were positive, but only 4/78 (5.1%) were positive in both duplicates, representing a total of 3/36 (8.3%) children with an additional rtPCR‐positive sample, only one of whom was persistently negative by ELISA. One child with a transient infection had two positive rtPCR reactions despite negative ELISA samples.Conclusions: In H. pylori noninfected or transiently infected children, as determined by stool ELISA, additional ELISA‐negative/rtPCR‐positive stool samples were found in 8.3% of children, but a possible persistent infection was only identified in 2.7% of children. Thus, the characterization of infection dynamics in children is not being misrepresented by application of stool ELISA. Furthermore, rtPCR does not significantly improve dynamic characterization.

Background. Helicobacter pylori, the main cause of peptic ulcer disease and gastric cancer in adult populations, is generally acquired during the first years of life. Infection can be persistent or transient and bacterial and host factors determining persistence are largely unknown and may prove relevant for future disease. Methods. Two cohorts of healthy Chilean infants (313 total) were evaluated every 3 months for 18–57 months to determine pathogen- and host-factors associated with persistent and transient infection. Results. One-third had at least one positive stool ELISA by age 3, with 20% overall persistence. Persistent infections were acquired at an earlier age, associated with more household members, decreased duration of breastfeeding, and nonsecretor status compared to transient infections. The cagA positive strains were more common in persistent stools, and nearly 60% of fully characterized persistent stool samples amplified cagA/vacAs1m1. Persistent children were more likely to elicit a serologic immune response, and both infection groups had differential gene expression profiles, including genes associated with cancer suppression when compared to healthy controls. Conclusions. These results indicate that persistent H. pylori infections acquired early in life are associated with specific host and/or strain profiles possibly associated with future disease occurrence.