Prevalence of Helicobacter pylori infection among resettled refugees presenting to a family medicine clinic in the United States

Abstract Background Although endemic to much of the global population, few studies have examined Helicobacter pylori (H. pylori) in US refugee populations. This study investigates the prevalence of H. pylori infection and barriers to treatment in the International Family Medicine Clinic (IFMC), a primary care refugee clinic, in central Virginia. Materials and Methods We conducted a chart review of 188 refugee patients of the IFMC who were referred for an H. pylori test between January 1, 2019, and December 31, 2020. Recorded measures included patient demographics, H. pylori test result, treatment of initial infection, completion of test of cure (TOC), TOC results, salvage therapy, and barriers to treatment. Binary logistic regression was performed to examine the association between demographic factors and H. pylori test results. Results Of the 171 patients who completed an H. pylori test, 94 tested positive (54.9%). Of the 93 patients that were subsequently treated, 76 were treated with clarithromycin triple therapy (82%). Forty‐eight patients (52%) completed a TOC after completing treatment, and 21 (43%) of these patients remained positive, indicating persistent infection. Eighteen patients (90%) who remained positive for H. pylori were subsequently treated with quadruple therapy. Patients under 18 (OR = 0.25, p < 0.01) and patients with a history of previous H. pylori (OR = 0.44, p < 0.05) were less likely to have positive results on initial H. pylori testing. Common barriers to treatment included pregnancy, religious observance (e.g., fasting), and health system complications (e.g., prior authorization for medications, cost of treatment). Conclusions The prevalence of H. pylori among refugees at the IFMC was higher than the overall prevalence estimate for the United States, which is consistent with previous studies. This work represents an updated picture of H. pylori prevalence among refugees in the United States and contributes to the identification of treatment barriers.


| INTRODUC TI ON
Helicobacter pylori (H. pylori) is a gram-negative, rod-shaped bacterium that infects the epithelial lining of the stomach and underlies one of the most common bacterial infections in humans. 1,2 Over half of the global population is infected, with the highest estimated prevalence in Africa (79.1%), Latin America and the Caribbean (63.4%), and Asia (54.7%), compared with lower prevalence in Northern America (37.1%) and Oceania (24.4%). 3 Infection is usually acquired in childhood. Risk factors include lower socioeconomic status or social disadvantage, male sex, and having multiple siblings (due to intra-familial spread). 2 It is thought that exposure to contaminated water is a possible source of transmission in developing countries.
In North America, prevalence is higher among certain racial and ethnic groups, including African Americans, Hispanic Americans, Native Americans, Canadian First Nations populations, and Alaska natives. 2 Immigrants to North America, especially those from Asia, Africa, and Central and South America, also have higher prevalence rates than those from North America. Additionally, those living near the United States (U.S.) border with Mexico are a higher-risk group. 2 Few studies have reported the prevalence of H. pylori in refugee populations worldwide, although prevalence in refugee source countries is high. [3][4][5] This is in contrast to the estimated prevalence of 35% in the U.S. general population based on a 2017 systematic review by Hooi et al. 3 The top origin countries for refugees resettled in the United States in 2020 were as follows: the Democratic Republic of Congo, Myanmar (Burma), Ukraine, Afghanistan, Iraq, and Syria; over the long term (2001-2019), most refugees have originated from Myanmar, Iraq, and Somalia. 6 While H. pylori prevalence has been overall decreasing in Western nations, immigrants and refugees are thought to have a prevalence similar to their counterparts in their native countries.
Although usually asymptomatic, H. pylori is considered a major cause of peptic ulcer disease (PUD) and gastritis. Treatment is important because those infected have an increased risk of developing gastric cancer and mucosal associated-lymphoid-type (MALT) lymphoma; 1 thus, all symptomatic adults found to have active infection should be offered treatment. 2 Furthermore, understanding common barriers to treatment and gaps in H. pylori treatment can guide future efforts to ensure refugee patients have access to appropriate care. In developing countries, most infections are acquired in childhood by the age of 5 years. Some children may spontaneously clear the infection but become reinfected. However, reinfection is less likely in children who acquired the initial infection in developed countries. 7 Among children, treatment is only recommended after a careful discussion of the risks and benefits with parents, as treatment is unlikely to improve abdominal symptoms other than those due to PUD, and there is a lower risk of progression to chronic complications compared with adults. 7,8 Aside from symptomatic PUD, testing for H. pylori infection has roles in the assessment of other conditions including refractory iron-deficiency anemia and immune thrombocytopenic purpura (ITP). 8 Testing can also be considered prior to starting chronic non-steroid anti-inflammatory drug (NSAID) therapy. 2 Screening for asymptomatic H. pylori infection is not currently routine in Western countries, despite some evidence that it may be cost-effective in certain populations. A study assessing the costeffectiveness of screening high-risk refugee and immigrant populations found that use of stool antigen testing through a general screening strategy, followed by treatment of positive cases, then retesting to confirm cure, is relatively cost-effective considering the number of gastric cancer and peptic ulcer cases averted. 9 This held true even at an H. pylori population prevalence as low as 25%. 9 Noninvasive diagnostic tests to confirm active infection include the urea breath test (UBT; FDA-approved for above age 3 years, with 85%-95% sensitivity and 85%-100% specificity) and fecal antigen test (94% sensitivity and 97% specificity regardless of age). 7 Both tests can also be used for confirming eradication after treatment and should be completed at least 4 weeks following antibiotics and 2 weeks after discontinuation of a proton pump inhibitor (PPI), due to potential for false negatives in presence of PPIs, or recent use of antibiotics or bismuth preparations. Serologic testing is not recommended for diagnostic nor eradication testing due to persistence of IgG antibodies long after infection has cleared, and lower reliability in children. However, as serologic testing is widely available, inexpensive, and less cumbersome for patients than UBT and fecal antigen testing, it may have a role in screening among high-risk populations. 2,10 Selection of a treatment regimen is guided by prior antibiotic exposure and information on prevalence of clarithromycin resistance.
Treatment failure is common due to increasing resistance of clarithromycin, metronidazole, and fluoroquinolones. 2 First-line triple therapy using a PPI, clarithromycin, and amoxicillin can be used. Due to increasing rates of clarithromycin resistance, however, the 2017 American College of Gastroenterology Clinical Guideline recommends bismuth quadruple therapy which includes a PPI, bismuth, metronidazole, and tetracycline as the preferred first-line regimen for most patients. 2 Among children, susceptibility testing is recommended prior to treatment. For strains that are clarithromycin-resistant or susceptibility is unknown, the recommended triple therapy regimen is PPI, amoxicillin, and metronidazole (or bismuth if metronidazole resistance is also unknown). 7 Because of the limited information on prevalence of H. pylori, treatment completion, and barriers to treatment in refugee populations, this study sought to address the following objectives: (1) estimate the prevalence and success of the treatment of H. pylori in refugee adult and pediatric patients attending a refugee primary care clinic, and (2) identify barriers to treatment. Given the potential long-term complications of H. pylori, this research can offer valuable insight to guide initiatives linking refugee patients to H. pylori treatment.

| Study setting and participants
The University of Virginia (UVA) Family Medicine clinic uniquely houses the International Family Medicine Clinic (IFMC). The IFMC serves as the primary care home for refugees and Special Immigrant Visa (SIV) holders (hereafter referred to as refugees) resettled in Charlottesville, VA, and the surrounding area. Since 2002, the clinic has served more than 4000 patients. The patient population hails from various countries including Afghanistan, the Democratic Republic of Congo, Nepal, Somalia, Myanmar, Iraq, and Syria. All refugee patients attending the clinic undergo a set of screening laboratory tests upon arrival. H. pylori testing is not included in this initial universal screening, but is ordered when clinical indications are identified at patient visits.
The IFMC manages a database in which all patients seen at the clinic have an "IFMC" flag in their chart. Using clinical encounter reports, we identified patients who had been referred for an H. pylori test between 2019 and 2020 using the electronic medical record (EMR). Patients were included in the study if they had an IFMC flag in the chart and if they had been referred for an H. pylori test during the study time period. The study was approved by the University of Virginia Health Sciences Institutional Review Board (IRB) and determined to be exempt from full IRB review, and therefore, informed consent was not required.

| Data collection
We obtained the following information from the EMR: age, sex, country of origin, country of exit, whether the patient had spent time in a refugee camp, primary language spoken, and previous his-

| Data analysis
Frequencies were obtained for patient characteristics including age group, sex, region of origin, region of exit, experience in refugee camp (yes/no), language (English/non-English), history of previous infection, H. pylori test result, treatment of initial infection, and completed TOC.
To simultaneously examine the influence of demographic factors on H. pylori test result (positive or negative), binary logistic regression was conducted, controlling for sex, age group, history of previous infection, language, and whether patient spent time in a refugee camp. Patients who had not completed their H. pylori test were removed due to low numbers. A second logistic regression was used to examine predictors of the need for a second course of antibiotics, controlling for sex, age group, history of previous infection, language, and whether patient spent time in a refugee camp. A subset of patients who tested positive on the initial H. pylori test and who completed the initial TOC were included. A positive TOC result was used to indicate whether a second round of antibiotics was needed.
Analyses were conducted in R 4.0.5 using the modelr package.
For all patients that tested positive for H. pylori, clinic visit notes were reviewed to extract information on any mentioned barriers that may have impacted completion of treatment. These barriers were reviewed and summarized.

| RE SULTS
In total, 188 IFMC patients were referred for an H. pylori test during the study period and 171 patients completed testing. Table 1  This included one patient who was prescribed lansoprazole, tinidazole, clarithromycin, and omeprazole, which was a continuation of a regimen prescribed before arriving to the United States; another patient was prescribed pantoprazole only for symptom management due to current pregnancy.
Among patients who completed testing, the overwhelming majority were from Afghanistan (country of origin for n = 122, 71%, and country of exit for n = 94, 56%), followed by Turkey (country of exit for n = 16, 9.5%), Democratic Republic of Congo (DRC; country of origin for n = 12, 7%), Nepal (country of exit for n = 11, 6.5%), Bhutan (country of origin for n = 9, 5.3%), and smaller numbers for Burundi, Tanzania, Iran, Iraq, Lebanon, Syria, India, Pakistan, Myanmar, Rwanda, Sudan, Colombia, Russia, and Thailand. Of note, some of these countries overlapped in patients' country of origin vs.   The results and outcomes of the TOC are presented in Table 2.

| CON CLUS ION
Our study found that the prevalence of H. pylori among refugees at a primary care refugee clinic was higher than the overall preva-

ACK N OWLED G M ENTS
The study was conducted within the Family Medicine Department of the University of Virginia. All authors meet authorship criteria in accordance with Helicobacter's authorship guidelines.

CO N FLI C T O F I NTE R E S T
The authors have no conflicts of interest to disclose. No external funding sources were used for this study.

AUTH O R CO NTR I B UTI O N S
The specific contributions of each author are as follows: All authors made substantial contributions to conception and design of the study and were involved in drafting the manuscript or revising it critically for important intellectual content; gave final approval of the version to be published and participated sufficiently in the work to take public responsibility for appropriate portions of the content; agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. N. Saif, N. Jensen, E.
Farrar, and S. Blackstone contributed to acquisition of the data and interpretation of the data. S. Blackstone conducted the data analysis.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available from the corresponding author upon reasonable request.