Disease Surveillance Among U.S.-Bound Immigrants and …

Discussion

During 2014–2019, approximately 3.5 million persons moved to the United States as an immigrant, a refugee, or an eligible other. Among immigrants, the number of arrivals and distribution of nationalities changed little over time. Among refugees and eligible others, both the number of arrivals and distribution of nationalities changed substantially from year to year; this variability follows U.S. policy decisions. The maximum number of refugees admitted for resettlement is determined by the U.S. president each year. Historically, the actual number of arrivals is equal to or just below that maximum, with some recent exceptions. For fiscal year 2017, the maximum was initially set at 110,000 by President Barack Obama (17) and was then decreased to 50,000 by a presidential executive order issued by President Donald Trump (18); the actual number of resettled refugees totaled 53,716 for that year (15). In fiscal year 2018, although the maximum was set at 45,000 (19), approximately one half this number of refugees were resettled after security enhancements were enacted by DHS, resulting in the lowest number of refugee admissions since fiscal year 1977 (15). Among eligible others, such as parolees or special immigrant visa holders, numbers and nationalities increase and decrease as programs start and stop. For example, the ending in 2017 of the so-called “wet-foot/dry-foot” policy (which allowed Cuban migrants who arrived in the United States [“dry foot”] without a visa to pursue residency a year later, whereas those intercepted at sea [“wet foot”] were returned to Cuba or resettled in a third country) (20) is reflected in the sharp decrease in the number of Cuban parolees in subsequent years. Because health profiles of refugees and eligible others differ by country of origin, country of residence, and local conditions before, during, and after leaving their home country, substantial changes in number and nationality can result in considerable changes in health and public health needs from year to year, posing significant operational challenges for optimizing, or even just preserving, public health programs and infrastructure for these populations, especially at the local level. CDC provides health profiles for each of the largest refugee groups resettling to the United States that describe the demographic, cultural, and health characteristics for each population and are intended to provide clinicians with knowledge needed to better serve these refugees (21).

Statutes to exclude non–U.S.-born persons from admission to the United States have been in place for more than a century. These statutes were codified to exclude those with “tuberculosis in any form, or with leprosy, or any contagious disease” in the Immigration and Nationality Act of 1952 and were recodified to exclude those with “a communicable disease of public health significance” (4) in accordance with regulations prescribed by the Secretary of HHS in the Immigration of Act of 1990. In 1991, the definition of a communicable disease of public health significance was limited to eight specified conditions: chancroid, gonorrhea, granuloma inguinale, HIV infection, infectious Hansen’s disease, lymphogranuloma venereum, infectious syphilis, and infectious TB (22). To allow for a more flexible, risk-based, and responsive approach grounded by medical and epidemiologic factors, this list was expanded in 2009 to include quarantinable communicable diseases, which are designated by a presidential executive order, and communicable PHEIC diseases that could be imported into the United States and affect U.S. residents (23). Finally, the list of eight specified conditions was reduced to four with the removal of HIV infection in 2010 (24), followed by the removal of chancroid, granuloma inguinale, and lymphogranuloma venereum in 2016 (25), leaving only infectious TB, infectious syphilis, gonorrhea, and infectious Hansen’s disease as the remaining specified conditions and the subjects of this report.

Tuberculosis

Eliminating TB in the United States, defined by the Advisory Committee for Elimination of Tuberculosis as a case rate of <1 per 1 million population, remains a major public health objective (26). Despite a historic low in U.S. TB incidence in 2019 of 2.7 cases per 100,000 population, the rate of decline has slowed in recent years (27). Persons not born in the United States account for more than two thirds of U.S. cases (27), and this proportion is increasing. Genotype studies suggest that most U.S. TB cases in non–U.S.-born persons are due to reactivation of LTBI, likely acquired abroad (28,29). CDC’s technical instructions are designed to 1) prevent importation of the disease by detecting and treating infectious TB disease (class A TB) before persons move to the United States and 2) reduce community transmission in the general U.S. population by identifying persons with conditions associated with increased risk for disease (class B TB) so that they can quickly receive testing and, if needed, preventive or curative treatment after moving.

EDN data are critical for monitoring implementation of the technical instructions and for evaluating the impact for continuous improvement. Before 2007, U.S.-bound immigrants, refugees, and eligible others were screened for TB by an algorithm based on sputum smear results. This algorithm was unable to identify persons entering the United States with TB disease with negative sputum smears but positive cultures, and a large proportion (one half to two thirds) of cases were likely being missed (30,31). To address this gap, CDC updated the technical instructions to require culture in addition to sputum smears and, for those with positive smear or culture test results, completion of a course of treatment administered by direct observation supervised by a panel physician. Started in 2007, full global implementation was achieved in 2013. A previous analysis of EDN data found that the annual number of smear-negative but culture-positive TB cases diagnosed during the overseas medical examination increased monotonically from four cases in 2007 to 629 in 2012, whereas annual TB cases detected among non–U.S.–born persons within the first year of arrival in the United States decreased from 1,511 to 940 cases, concurrent with overall decreases in the U.S. TB rates (27,30). In other words, by 2012, approximately 600 more cases were detected overseas at the same time 600 fewer were detected in the United States. This finding suggests that the culture-based algorithm detects substantially more cases, resulting in subsequent treatment, during the overseas medical examination process, thus reducing importation. However, the findings in this report indicate that during 2014–2019, among persons with an overseas classification of class B0 TB, pulmonary, or class B1 TB, pulmonary, the proportion with a subsequent postarrival diagnosis of culture-positive TB disease during their U.S. TB examination remained steady over time, suggesting that new gains will require new strategies. Finally, during this same period, the proportion of persons with class B TB for whom a postarrival TB examination was reported to EDN as completed was lowest in 2019, a particularly concerning finding because of the subsequent spread of SARS-CoV-2, the virus that causes COVID-19, which diverted focus and resources away from TB control and other routine public health measures at the local, state, and federal levels beginning in 2020 (32).

In October 2018, updates to the technical instructions introduced refinements to the TB classification schema for the overseas examination. After the update, persons with an initial diagnosis of TB disease who subsequently completed directly observed therapy under the supervision of a panel physician (class B0 TB, pulmonary) are distinguished from those who, during their initial examination, had signs, symptoms, or chest radiography suggestive of TB but negative results from smear and culture tests (class B1 TB, pulmonary). Before the change, the technical instructions aggregated both groups together (previously class B1 TB, pulmonary, for both). This report and others (33) show that persons who meet current criteria for class B1 TB, pulmonary, are more likely to receive a diagnosis of culture-positive TB disease at their postarrival follow-up examination than those meeting criteria for class B0 TB, pulmonary. Changes to the classification schema to reflect this risk difference might help U.S. health departments better stratify risk for improved patient management.

The technical instructions mandate testing for immune reactivity to M. tuberculosis by an interferon-gamma release assay (IGRA) or, before October 2018, by a tuberculin skin test (TST), for children aged 2–14 years in countries with ≥20 TB disease cases per 100,000 population and for persons (of any age in any country) known to have had contact for a prolonged period with a person with smear- or culture-positive TB disease. A person who has a positive TST or IGRA result but chest radiographs that do not suggest TB disease and no other signs or symptoms of disease or known HIV infection meets criteria for class B2 TB, LTBI evaluation. As such, EDN notifies the health department in the jurisdiction where the newly arriving person reports intending to live to facilitate a postarrival follow-up evaluation. A previous analysis of EDN data demonstrated that children who had a positive TST during their overseas examination were frequently (64%) retested during their postarrival evaluations and often received negative results; when retested by TST in the United States, 37% had a negative TST result, and when retested by IGRA in the United States, 74% had a negative IGRA result (Z Wang, MS, CDC, personal communication, November 2021). The high proportion of negative results when retested by IGRA likely reflects cross-reactivity to bacille Calmette-Guerin (BCG) vaccination (common in many immigrant and refugee populations) producing false-positive results in the initial overseas TST. That analysis also showed that the proportion who accepted treatment was higher after a positive IGRA retest (76%) than a positive TST retest (61%) (Z Wang, MS, CDC, personal communication, November 2021). In response, the 2018 technical instructions were changed from allowing testing by TST or IGRA overseas to allowing IGRA only (except in countries where no IGRAs are licensed). This report shows that, among children who met criteria for class B2 TB, LTBI evaluation, and completed a postarrival domestic evaluation, the proportion who received a domestic diagnosis of LTBI increased from 53% (or lower) for each of the previous 5 years to 62% in 2019, consistent with the change to IGRA only overseas. This change is expected to reduce the amount of unnecessary follow-up care required by state health departments while increasing the number of persons treated.

Syphilis

Syphilis remains a major public health threat, and infection rates are increasing in the United States (34). Screening overseas has remained consistent since the early 1990s, requiring first a nontreponemal serologic test (either the rapid plasma reagin or Venereal Disease Research Laboratory test) and, if positive, a treponemal test performed on the same blood specimen for confirmation. A 2014 update to the technical instructions required panel physicians to identify the stage of disease, and a 2017 update expanded the available list of confirmatory tests that panel physicians may use. Compared with primary and secondary syphilis rates reported by age group for the U.S. general population in 2018 (34), the findings in this report indicate that rates were lower for refugees and eligible others aged 15–19, 20–24, and 25–29 years, similar to rates among those aged 30–34 years; more than twice as high as rates among those aged 35–39 and 40–44 years; and more than five times as high as rates among those aged 45–54, 55–64, and ≥65 years. In other words, among younger adults, primary and secondary syphilis rates were lower among refugees and eligible others than among similarly aged persons in the U.S. general population; among older adults, the opposite was observed. This phenomenon could reflect a bias in the United States toward selecting for testing those perceived as most at risk (younger adults), leaving older adults undertested, whereas all refugees and eligible others are tested regardless of age. However, the absolute number of primary and secondary syphilis cases detected annually by universal overseas screening of refugees and eligible others aged >14 years is small, ranging from one case in 2019 to 24 cases in 2015.

Gonorrhea

Gonorrhea is the second most common sexually transmitted infection in the United States (34). Historically, panel physicians relied on the medical history and physical examination findings to diagnose gonorrhea. However, because many infections are asymptomatic, in 2016, CDC issued technical instructions that require laboratory testing. Panel physicians perform a nucleic acid amplification test, typically with a urine sample. Compared with gonorrhea rates reported by age group for the U.S. general population in 2018 (34), rates for refugees and eligible others were lower or similar for every 5-year age group among persons aged 15–44 years, three times higher among those aged 45–54 years, and six times higher among those aged 55–64 years, similar to the pattern observed for primary and secondary syphilis. However, even among refugees and eligible others, rates were highest among younger adults (15–34 years), ranging from 289 to 668 cases per 100,000 persons with test results, and lowest among adults aged ≥35 years, ranging from 0 to 234 cases per 100,000 persons with test results. Young adults remain at greatest risk for gonorrhea. Overall, the number of gonorrhea cases identified by the addition of laboratory testing is small, with 58 cases detected in 2018 and 73 cases in 2019.

Hansen’s Disease

Hansen’s disease is rare among refugees and eligible others. However, this disease still occurs in many places, including within pockets of the United States (35). In 2014, the technical instructions clarified the need to follow World Health Organization (WHO) treatment regimens for infected persons. In addition, because patients are considered noninfectious after at least 7 days of therapy, according to the WHO protocol (36), immigrants, refugees, and eligible others are allowed to travel while receiving therapy to the United States. EDN sends a separate notification to the U.S. Hansen’s Disease Center in Louisiana for the small number of new arrivals (25 cases in 6 years) admitted with Hansen’s disease.

Vaccination Program for Refugees

The overseas medical examination exists to satisfy statutory requirements (4). However, these required medical encounters also offer an opportunity to introduce voluntary public health interventions. Refugees, unlike immigrants, are not required to receive vaccines before arriving in the United States. When unvaccinated or undervaccinated persons are concentrated together, outbreaks of vaccine-preventable diseases are likely. Outbreaks affecting U.S.-bound refugees overseas have caused preventable illnesses and deaths, led to disease importation and spread in the United States, created costly operational disruptions for the U.S. government resettlement programs, and necessitated costly public health responses by U.S. health agencies (8,37). The vaccination program for U.S.-bound refugees offers 11 vaccines that help prevent 14 diseases. An important priority, as measles cases increase worldwide, is to offer all refugees at least 1 dose of measles-containing vaccine before they arrive in the United States. First-dose coverage with measles-containing vaccine increased from 49% in 2014 to 96% in 2019, and the majority of those not vaccinated in 2019 had a contraindication that precluded vaccination.

The advantages of administering vaccinations before instead of after resettlement include providing protection in settings of higher risk, when it is most needed; avoiding costly disruptions to resettlement; reducing the risk for disease importation; reducing the number of vaccinations state health departments and resettlement agencies must provide (38); and reducing the number of vaccinations needed by refugees during the immediate, and often challenging, postarrival period. A critical component of the vaccination program for refugees is ensuring that the EDN record of vaccines received overseas is available when needed in the United States. A previous analysis showed that the EDN record is routinely available at the follow-up evaluation conducted by state health departments shortly after a refugee arrives but might not be available beyond this point (39). In 2015, CDC began working with states to add EDN records to state immunization information systems (IIS), which combine vaccination information from different providers into a single consolidated record. As of 2019, EDN records are transferred to IIS in Colorado, Connecticut, Iowa, Kentucky, Maryland, Massachusetts, Minnesota, Nebraska, New York, Tennessee, and Wisconsin. Supplementing IIS with data from EDN allows states to calculate coverage statistics for refugees more easily and provides a more accurate vaccination history.

Presumptive Treatment for Refugees

Parasitic infections are among the most common infections worldwide, especially in areas with inadequate sanitation (40,41). CDC recommends numerous presumptive antiparasitic treatments for refugees, including albendazole for soil-transmitted helminthiases, ivermectin for strongyloidiasis (in countries where L. loa is not endemic), and praziquantel for schistosomiasis (42). CDC also recommends presumptive treatment for P. falciparum infection with artemether-lumefantrine for U.S.-bound refugees from parts of sub-Saharan Africa where malaria is endemic. Refugees originating from areas where malaria is not endemic are unlikely to have asymptomatic or subclinical P. falciparum infection and can therefore receive directed treatment, if needed, overseas or in the United States (43).

Although the risk for spread from imported infections in the United States is low, untreated helminth infections can persist for decades and cause significant harm to the infected persons. Strongyloidiasis can become serious or fatal when disseminated disease occurs (44). Chronic schistosomiasis can have significant clinical consequences, including infertility, liver and kidney failure, and bladder cancer (45). Untreated malaria can lead to severe illness and death (46). This report shows that the presumptive treatment program provides adequate coverage; other analyses have shown that presumptive treatment of U.S.-bound refugees during the overseas medical examination reduces or eliminates parasitic infections for most U.S.-bound refugees (47–49) and is cost-effective (50). Unlike the vaccination program, which offers vaccination to all refugees, presumptive treatment is only offered in certain countries when the benefit outweighs the risk, considering such factors as the epidemiologic risk for infection, severity of outcomes if untreated, adverse event profile of the chemotherapeutic agent, availability and accuracy of testing after arrival, and access to affordable treatment in the United States.

Program Improvements

Beginning in 1995, notifications of newly arrived immigrants and refugees were sent to state health departments via the U.S. Postal Service. With the inception of the EDN system in 2008, notifications began to be sent electronically. For refugees and most Iraqi and Afghan special immigrant visa holders, EDN receives overseas medical examination data electronically directly from IOM, the agency that conducts examinations and coordinates travel for most refugees and special immigrant visa holders. For immigrants, collection of overseas medical data historically has involved transferring paper records from immigrants with a medical classification to DHS and then to CDC at U.S. ports of entry and then shipping the paper records to CDC headquarters for manual data entry. This process has taken up to 4 weeks, resulting in delays in the notifications sent to state and local health departments, causing losses to follow-up. In 2018, CDC, in collaboration with DOS, launched the U.S. version of eMedical, a system for processing overseas medical examination data for immigrants. Panel physicians enter data directly into the eMedical system, and the data are transferred to the EDN system within 2 days of the immigrant’s arrival in the United States. The substantial reduction in record-processing time increases the likelihood that health departments will be able to initiate timely follow-up with new-arrival immigrants. Finally, eMedical is used to collect data for all new-arrival immigrants, rather than just for those who arrive with a medical classification.