Worldwide, an unprecedented 65 million people—approximately 1% of the world’s population—are forcibly displaced.¹ Since 1975, the United States has resettled more than three million refugees, with 85,000 arriving in 2016.² United States–bound refugees have three organized health encounters during resettlement: 1) required initial overseas examination, performed 2–6 months before travel to detect and treat “inadmissible” public health conditions (primarily tuberculosis [TB]). The required elements of this examination include medical history (including history of mental health or substance abuse issues), complete physical examination, evaluation for TB either by tuberculin skin test or chest X-ray (depending on age), laboratory testing for gonorrhea and syphilis, and screening for other communicable diseases of public health concern when applicable³; 2) predeparture examinations for fitness-to-travel and presumptive treatment of soil-transmitted helminths (STH) and Strongyloides, usually conducted 3–5 days pretravel by physicians from the International Organization for Migration (IOM)⁴; and 3) voluntary domestic medical examinations, performed by U.S. state or local health departments within 90 days after arrival.⁴ The Centers for Disease Control and Prevention (CDC) provides recommendations for domestic examination, but implementation varies by state.

CDC, the U.S. Department of State, and IOM have developed supplemental overseas health programs, including vaccination and presumptive STH treatment to improve and protect public and individual migrant health.⁴ These cost-saving interventions harmonize health services for refugees originating from the same areas and reduce burden on domestic providers.⁵

In 2012, we implemented a program evaluation, assessing the feasibility and impact of overseas identification and management of selected, common medical conditions beyond the scope of the required examination. To our knowledge, this is the first large-scale prospective evaluation of medical and preventive health interventions in a migrating population.

During the initial overseas medical examination, we offered voluntary testing and management for anemia, hepatitis B virus (HBV) infection, and intestinal parasites to a convenience sample of U.S.-bound refugees aged ≥ 6 months living in three camps on the Thailand–Burma border. These conditions were chosen because of their known high prevalence in this region^6–8 and the potential to improve travel fitness or prevent disease by early screening or intervention. The 6-month age cutoff was chosen because physiologic anemia can occur in younger infants.⁹ Written consent was obtained from participants ≥ 15 years of age and parents or guardians of those < 15 years old (during the overseas medical examination process, refugees ≥ 15 years old are considered adults). Blood and stool samples were collected during the three examinations previously described (Supplemental Figure 1). Initial and predeparture time points were defined by dates of first and last examinations overseas, respectively, as repeat medical examinations were required for participants who did not depart within 6 months of the initial examination. Participants with identified medical conditions underwent management and evaluation based on clinical judgment and algorithms (Supplemental Figures 2–4, Supplemental Table 1). To facilitate follow-up, results were communicated to U.S. state refugee health programs directly via secure fax. States sent available, domestic examination results to CDC.

We offered enrollment to all 3,419 U.S.-bound refugees having initial medical examinations during July 9, 2012 to November 29, 2013 and enrolled 57% (2,004) (Table 1). Among participants, 42% (848) were < 18 years old and 52% (1,038) were male (Table 1). Complete or partial results were available for all participants at initial, 89% (1,794) at predeparture, and 39% (777) at domestic examinations. Median time between initial and predeparture time points was 167 days (interquartile range [IQR]: 135–326; min–max: 33–1,013), and 35 days between predeparture and domestic examinations (IQR: 27–50; min–max: 11–393).

This evaluation demonstrated that selected public health services, including intestinal parasite treatment, are logistically feasible and can improve health for refugees in the 2- to 6-month overseas resettlement processing window.

Our HBV screening algorithm was implemented successfully, and it identified asymptomatic patients with significant liver disease. The high (≥ 8%) prevalence of HBV infection was consistent with regional trends.¹⁵ Perinatal exposure, a common mode of transmission in high-prevalence settings,¹⁶ likely did not explain all cases, as evidenced by the higher proportion of HBV-infected males. No children < 8 years tested positive, likely due to successful camp-based vaccination programs.¹⁷ Early diagnosis offered an opportunity for counseling, initial management, and vaccination of contacts, and facilitated domestic follow-up.

The success and cost-benefit estimates of pre-vaccination HBsAg testing led to its incorporation into the Vaccination Program for U.S.-bound Refugees.^18–20 This strategy may contribute to the elimination of HBV transmission in the United States²¹ and could be considered for other U.S.-bound populations, including immigrants, asylees, and other long-term visitors, such as students and workers.

The intensity and prevalence of intestinal helminths and eosinophilia decreased following presumptive STH treatment. Infection caused by Strongyloides, estimated to affect up to 46% of U.S.-bound refugees,⁷ is often asymptomatic and unrecognized, but can persist indefinitely if untreated. Immunosuppression, especially with corticosteroids, can result in fatal hyperinfection years after leaving an endemic area.^22,23 Standard serologic and stool tests have poor predictive value in detecting active infection.²⁴ The low prevalence of positive stool agar—thought to be a sensitive test²⁵—or Strongyloides qPCR, may indicate that some of the 14% who were seropositive were not actively infected. Although eosinophilia was associated with positive Strongyloides MBA and stool qPCR, up to one-third of people testing positive were not eosinophilic, indicating that eosinophilia does not reliably predict infection.^26,27 This assessment compares pre- and posttreatment stool and blood analyses and supports the effectiveness of mass treatment of Strongyloides with ivermectin.²⁸ Presumptive STH and Strongyloides treatment has been shown to be cost-saving,^5,29 even before the recent spike in anti-parasitic drug prices in the United States.²⁹ Of note, standard-dose albendazole is minimally effective and ivermectin ineffective against protozoa (primarily, giardiasis), and significant changes in protozoan infections were neither expected nor observed. Protozoan infections are believed to have less direct public health impact in these populations,³⁰ although the relationship between specific protozoans, such as Giardia, and malnutrition could be further explored.³¹

Identification and management of anemia overseas was associated with improved Hgb at predeparture. Severe anemia may place an individual at risk of decompensation during air travel (“fitness-to-fly”), as highlighted by the death of a refugee child while en-route to the United States in 2008 (M. Weinberg, CDC, unpublished data). However, although ancillary testing was helpful in determining anemia etiologies, it was time- and resource-intensive. In treated participants, Hgb increased significantly, but overall anemia prevalence for the group as a whole did not change. Targeted testing of high-risk groups—such as young children, women of childbearing age, and malnourished patients—may be of most benefit in this setting. Based on the predominance of iron-deficiency anemia—even among those with thalassemia/trait—an initial trial of iron or multivitamin-with-iron therapy, followed by investigation if the anemia fails to improve, may be reasonable. Caution is warranted if this approach is adopted in populations with higher malaria prevalence.^32,33

Our results support camp survey findings of decreasing rates of acute malnutrition among children < 5 years, likely attributable to long-term camp nutritional programs, although high rates of stunting and anemia persist.^34,35 Improvements in nutritional status among children were seen even in the short interval before departure. Further investigation may be warranted to determine whether presumptive STH treatment contributed to linear growth. Domestic results supported sustained growth improvements over time. A standard operating procedure for identification and management of moderate-to-severe acute malnutrition, based on the nutrition and anemia modules of this project, is in the process of rollout in several sites overseas.

A limitation of our evaluation was the lack of an untreated control group, due to programmatic and ethical considerations. For intestinal parasites, the possibility of re-infection between initial and predeparture examinations—which occurred in some participants (Figure 4)—was addressed by repeating presumptive STH treatment predeparture. By arrival, participants had received two courses of treatment, rather than the one predeparture course usually offered during resettlement. However, a decreased prevalence of intestinal parasites was already seen at predeparture. Also, because refugees disperse to 49 states after arrival in the United States, partial or complete domestic data were available for only 39% (777) of participants. Furthermore, laboratory testing and results available from different participating states differed based on each state’s medical examination requirements and procedures. However, all qPCR and MBA testing was performed using uniform methods at the same laboratories.

More than one-third of the U.S. states participated in this pilot. We maintained in close contact with participating states throughout, including during periodic conference calls to share findings and other updates; by direct communication with states and specific providers regarding urgent or complex cases (e.g., patients with chronic HBV infection who had evidence of liver damage) and during presentation of results and updates during annual conferences.

Several individuals, including some with life-threatening diagnoses, benefitted from earlier diagnoses and communication of health information to receiving states. However, in other instances, timely communication of overseas information was hindered by logistical challenges, including delayed documentation and electronic record transfer. It was sometimes impossible to obtain follow-up information once participants dispersed to U.S. clinics and health-care systems—highlighting the programmatic benefit of screening and delivery of simple, cost-saving interventions before arrival, and the value of optimizing health communication through the migration continuum. Continuity of care—and, therefore, access to medical data—across the resettlement process is crucial. Further exploration is needed, in collaboration with state partners, to identify best practices in documentation, patient education, and communication of health information across borders.

United States–bound refugees resettle from diverse countries and temporary asylum conditions. Health-care access and health condition prevalence vary by population. Tailoring interventions to population-specific needs, such as targeted anemia screening and selection of antiparasitic therapies, is necessary (e.g., refugees resettling from sub-Saharan Africa also receive praziquantel and artemether–lumifantrine to treat schistosomiasis and malaria, respectively⁸). Our challenge is to identify and implement those manageable, cost-effective services that would most benefit resettling refugees and provide state partners with earlier health information. In addition, clinicians who serve refugees after arrival to the United States should be aware of common conditions affecting resettling refugee populations and familiarize themselves with CDC guidance regarding screening and management of newly arrived refugees.⁴ Furthermore, they should review each refugee’s overseas medical forms and be familiar with existing predeparture interventions, such as vaccination and presumptive STH and Strongyloides treatment.^7,8

Although interventions requiring longer term follow-up—such as anemia treatment and retesting, and workup and referrals for hepatitis B-positive patients—it may not be feasible in less stable settings, some of the screening we conducted relied upon, or could be accomplished using, point-of-care rapid testing. For example, pre-vaccination hepatitis B testing was conducted using a rapid test kit and counseling of positive individuals and vaccination of susceptible people can be done on the spot; although we had access to CBC in our setting, anemia screening can also be conducted using HemoCue^®. Presumptive STH treatment with albendazole is relatively inexpensive outside of the United States and can be accomplished during a single session. Furthermore, nutritional and anthropometric assessments for children have long been used as measures of population health in unstable emergency settings³⁶ and can help community and other aid agencies identify and triage those individuals needing the most acute medical intervention.

This account of our experience in implementing and assessing the impact of enhanced health screening and interventions for U.S.-bound refugees may be useful to countries resettling some of the 65 million displaced persons worldwide, as we address the shared global challenge of ensuring healthy migration for refugees and health protection for receiving communities.