Effect of Predeparture Testing on Postarrival SARS-CoV-2-Positive Test Results Among International Travelers - CDC Traveler-Based Genomic Surveillance Program, Four U.S. Airports, March-September 2022.

Beginning December 6, 2021, all international air passengers boarding flights to the United States were required to show either a negative result from a SARS-CoV-2 viral test taken ≤1 day before departure or proof of recovery from COVID-19 within the preceding 90 days (1). As of June 12, 2022, predeparture testing was no longer mandatory but remained recommended by CDC (2,3). Various modeling studies have estimated that predeparture testing the day before or the day of air travel reduces transmission or importation of SARS-CoV-2 by 31%-76% (4-7). Postarrival SARS-CoV-2 pooled testing data from CDC's Traveler-based Genomic Surveillance program were used to compare SARS-CoV-2 test results among volunteer travelers arriving at four U.S. airports during two 12-week periods: March 20-June 11, 2022, when predeparture testing was required, and June 12-September 3, 2022, when predeparture testing was not required. In a multivariable logistic regression model, pooled nasal swab specimens collected during March 20-June 11 were 52% less likely to be positive for SARS-CoV-2 than were those collected during June 12-September 3, after adjusting for COVID-19 incidence in the flight's country of origin, sample pool size, and collection airport (adjusted odds ratio [aOR] = 0.48, 95% CI = 0.39-0.58) (p<0.001). These findings support predeparture testing as a tool for reducing travel-associated SARS-CoV-2 transmission and provide important real-world evidence that can guide decisions for future outbreaks and pandemics.

Early Detection of Severe Acute Respiratory Syndrome Coronavirus 2 Variants Using Traveler-based Genomic Surveillance at 4 US Airports, September 2021-January 2022.

We enrolled arriving international air travelers in a severe acute respiratory syndrome coronavirus 2 genomic surveillance program. We used molecular testing of pooled nasal swabs and sequenced positive samples for sublineage. Traveler-based surveillance provided early-warning variant detection, reporting the first US Omicron BA.2 and BA.3 in North America.

Cruise Ship Travel in the Era of Coronavirus Disease 2019 (COVID-19): A Summary of Outbreaks and a Model of Public Health Interventions.

BACKGROUND: Cruise travel contributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission when there were relatively few cases in the United States. By 14 March 2020, the Centers for Disease Control and Prevention (CDC) issued a No Sail Order suspending US cruise operations; the last US passenger ship docked on 16 April. METHODS: We analyzed SARS-CoV-2 outbreaks on cruises in US waters or carrying US citizens and used regression models to compare voyage characteristics. We used compartmental models to simulate the potential impact of 4 interventions (screening for coronavirus disease 2019 (COVID-19) symptoms; viral testing on 2 days and isolation of positive persons; reduction of passengers by 40%, crew by 20%, and reducing port visits to 1) for 7-day and 14-day voyages. RESULTS: During 19 January to 16 April 2020, 89 voyages on 70 ships had known SARS-CoV-2 outbreaks; 16 ships had recurrent outbreaks. There were 1669 reverse transcription polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infections and 29 confirmed deaths. Longer voyages were associated with more cases (adjusted incidence rate ratio, 1.10, 95% confidence interval [CI]: 1.03-1.17, P < .003). Mathematical models showed that 7-day voyages had about 70% fewer cases than 14-day voyages. On 7-day voyages, the most effective interventions were reducing the number of individuals onboard (43.3% reduction in total infections) and testing passengers and crew (42% reduction in total infections). All four interventions reduced transmission by 80.1%, but no single intervention or combination eliminated transmission. Results were similar for 14-day voyages. CONCLUSIONS: SARS-CoV-2 outbreaks on cruises were common during January-April 2020. Despite all interventions modeled, cruise travel still poses a significant SARS-CoV-2 transmission risk.

Multidrug-Resistant Tuberculosis in U.S.-Bound Immigrants and Refugees.

Rationale: Approximately two-thirds of new cases of tuberculosis (TB) in the United States are among non-U.S.-born persons. Culture-based overseas TB screening in U.S.-bound immigrants and refugees has substantially reduced the importation of TB into the United States, but it is unclear to what extent this program prevents the importation of multidrug-resistant TB (MDR-TB). Objectives: To study the epidemiology of MDR-TB in U.S.-bound immigrants and refugees and to evaluate the effect of culture-based overseas TB screening in U.S.-bound immigrants and refugees on reducing the importation of MDR-TB into the United States. Methods: We analyzed data of immigrants and refugees who completed overseas treatment for culture-positive TB during 2015-2019. We also compared mean annual number of MDR-TB cases in non-U.S.-born persons within 1 year of arrival in the United States between 1996-2006 (when overseas screening followed a smear-based algorithm) and 2014-2019 (after full implementation of a culture-based algorithm). Results: Of 3,300 culture-positive TB cases identified by culture-based overseas TB screening in immigrants and refugees during 2015-2019, 122 (3.7%; 95% confidence interval [CI], 3.1-4.1) had MDR-TB, 20 (0.6%; 95% CI, 0.3-0.9) had rifampicin-resistant TB, 382 (11.6%; 95% CI, 10.5-12.7) had isoniazid-resistant TB, and 2,776 (84.1%; 95% CI, 82.9-85.4) had rifampicin- and isoniazid-susceptible TB. None were diagnosed with extensively drug-resistant TB. All 3,300 persons with culture-positive TB completed treatment overseas; of 70 and 11 persons who were treated overseas for MDR-TB and rifampicin-resistant TB, respectively, none were diagnosed with TB disease at postarrival evaluation in the United States. Culture-based overseas TB screening in U.S.-bound immigrants and refugees prevented 24.4 MDR-TB cases per year from arriving in the United States, 18.2 cases more than smear-based overseas TB screening. The mean annual number of MDR-TB cases among non-U.S.-born persons within 1 year of arrival in the United States decreased from 34.6 cases in 1996-2006 to 19.5 cases in 2014-2019 (difference of 15.1; P < 0.001). Conclusions: Culture-based overseas TB screening in U.S.-bound immigrants and refugees substantially reduced the importation of MDR-TB into the United States.

Reducing travel-related SARS-CoV-2 transmission with layered mitigation measures: symptom monitoring, quarantine, and testing.

BACKGROUND: Balancing the control of SARS-CoV-2 transmission with the resumption of travel is a global priority. Current recommendations include mitigation measures before, during, and after travel. Pre- and post-travel strategies including symptom monitoring, antigen or nucleic acid amplification testing, and quarantine can be combined in multiple ways considering different trade-offs in feasibility, adherence, effectiveness, cost, and adverse consequences. METHODS: We used a mathematical model to analyze the expected effectiveness of symptom monitoring, testing, and quarantine under different estimates of the infectious period, test-positivity relative to time of infection, and test sensitivity to reduce the risk of transmission from infected travelers during and after travel. RESULTS: If infection occurs 0-7 days prior to travel, immediate isolation following symptom onset prior to or during travel reduces risk of transmission while traveling by 30-35%. Pre-departure testing can further reduce risk, with testing closer to the time of travel being optimal even if test sensitivity is lower than an earlier test. For example, testing on the day of departure can reduce risk while traveling by 44-72%. For transmission risk after travel with infection time up to 7 days prior to arrival at the destination, isolation based on symptom monitoring reduced introduction risk at the destination by 42-56%. A 14-day quarantine after arrival, without symptom monitoring or testing, can reduce post-travel risk by 96-100% on its own. However, a shorter quarantine of 7 days combined with symptom monitoring and a test on day 5-6 after arrival is also effective (97--100%) at reducing introduction risk and is less burdensome, which may improve adherence. CONCLUSIONS: Quarantine is an effective measure to reduce SARS-CoV-2 transmission risk from travelers and can be enhanced by the addition of symptom monitoring and testing. Optimal test timing depends on the effectiveness of quarantine: with low adherence or no quarantine, optimal test timing is close to the time of arrival; with effective quarantine, testing a few days later optimizes sensitivity to detect those infected immediately before or while traveling. These measures can complement recommendations such as social distancing, using masks, and hand hygiene, to further reduce risk during and after travel.

Coronavirus Disease 2019 (COVID-19) in Americans Aboard the Diamond Princess Cruise Ship.

BACKGROUND: The Diamond Princess cruise ship was the site of a large outbreak of coronavirus disease 2019 (COVID-19). Of 437 Americans and their travel companions on the ship, 114 (26%) tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We interviewed 229 American passengers and crew after disembarkation following a ship-based quarantine to identify risk factors for infection and characterize transmission onboard the ship. RESULTS: The attack rate for passengers in single-person cabins or without infected cabinmates was 18% (58/329), compared with 63% (27/43) for those sharing a cabin with an asymptomatic infected cabinmate, and 81% (25/31) for those with a symptomatic infected cabinmate. Whole genome sequences from specimens from passengers who shared cabins clustered together. Of 66 SARS-CoV-2-positive American travelers with complete symptom information, 14 (21%) were asymptomatic while on the ship. Among SARS-CoV-2-positive Americans, 10 (9%) required intensive care, of whom 7 were ≥70 years. CONCLUSIONS: Our findings highlight the high risk of SARS-CoV-2 transmission on cruise ships. High rates of SARS-CoV-2 positivity in cabinmates of individuals with asymptomatic infections suggest that triage by symptom status in shared quarters is insufficient to halt transmission. A high rate of intensive care unit admission among older individuals complicates the prospect of future cruise travel during the pandemic, given typical cruise passenger demographics. The magnitude and severe outcomes of this outbreak were major factors contributing to the Centers for Disease Control and Prevention's decision to halt cruise ship travel in US waters in March 2020.

Cost effectiveness analysis of implementing tuberculosis screening among applicants for non-immigrant U.S. work visas.

BACKGROUND: While persons who receive immigrant and refugee visas are screened for active tuberculosis before admission into the United States, nonimmigrant visa applicants (NIVs) are not routinely screened and may enter the United States with infectious tuberculosis. OBJECTIVES: We evaluated the costs and benefits of expanding pre-departure tuberculosis screening requirements to a subset of NIVs who arrive from a moderate (Mexico) or high (India) incidence tuberculosis country with temporary work visas. METHODS: We developed a decision tree model to evaluate the program costs and estimate the numbers of active tuberculosis cases that may be diagnosed in the United States in two scenarios: 1) "Screening": screening and treatment for tuberculosis among NIVs in their home country with recommended U.S. follow-up for NIVs at elevated risk of active tuberculosis; and, 2) "No Screening" in their home country so that cases would be diagnosed passively and treatment occurs after entry into the United States. Costs were assessed from multiple perspectives, including multinational and U.S.-only perspectives. RESULTS: Under "Screening" versus "No Screening", an estimated 179 active tuberculosis cases and 119 hospitalizations would be averted in the United States annually via predeparture treatment. From the U.S.-only perspective, this program would result in annual net cost savings of about $3.75 million. However, rom the multinational perspective, the screening program would cost $151,388 per U.S. case averted for Indian NIVs and $221,088 per U.S. case averted for Mexican NIVs. CONCLUSION: From the U.S.-only perspective, the screening program would result in substantial cost savings in the form of reduced treatment and hospitalization costs. NIVs would incur increased pre-departure screening and treatment costs.

Risk Assessment and Management of COVID-19 Among Travelers Arriving at Designated U.S. Airports, January 17-September 13, 2020.

In January 2020, with support from the U.S. Department of Homeland Security (DHS), CDC instituted an enhanced entry risk assessment and management (screening) program for air passengers arriving from certain countries with widespread, sustained transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). The objectives of the screening program were to reduce the importation of COVID-19 cases into the United States and slow subsequent spread within states. Screening aimed to identify travelers with COVID-19-like illness or who had a known exposure to a person with COVID-19 and separate them from others. Screening also aimed to inform all screened travelers about self-monitoring and other recommendations to prevent disease spread and obtain their contact information to share with public health authorities in destination states. CDC delegated postarrival management of crew members to airline occupational health programs by issuing joint guidance with the Federal Aviation Administration.* During January 17-September 13, 2020, a total of 766,044 travelers were screened, 298 (0.04%) of whom met criteria for public health assessment; 35 (0.005%) were tested for SARS-CoV-2, and nine (0.001%) had a positive test result. CDC shared contact information with states for approximately 68% of screened travelers because of data collection challenges and some states' opting out of receiving data. The low case detection rate of this resource-intensive program highlighted the need for fundamental change in the U.S. border health strategy. Because SARS-CoV-2 infection and transmission can occur in the absence of symptoms and because the symptoms of COVID-19 are nonspecific, symptom-based screening programs are ineffective for case detection. Since the screening program ended on September 14, 2020, efforts to reduce COVID-19 importation have focused on enhancing communications with travelers to promote recommended preventive measures, reinforcing mechanisms to refer overtly ill travelers to CDC, and enhancing public health response capacity at ports of entry. More efficient collection of contact information for international air passengers before arrival and real-time transfer of data to U.S. health departments would facilitate timely postarrival public health management, including contact tracing, when indicated. Incorporating health attestations, predeparture and postarrival testing, and a period of limited movement after higher-risk travel, might reduce risk for transmission during travel and translocation of SARS-CoV-2 between geographic areas and help guide more individualized postarrival recommendations.

Tuberculosis among Newly Arrived Immigrants and Refugees in the United States.

Rationale: U.S. health departments routinely conduct post-arrival evaluation of immigrants and refugees at risk for tuberculosis (TB), but this important intervention has not been thoroughly studied.Objectives: To assess outcomes of the post-arrival evaluation intervention.Methods: We categorized at-risk immigrants and refugees as having had recent completion of treatment for pulmonary TB disease overseas (including in Mexico and Canada); as having suspected TB disease (chest radiograph/clinical symptoms suggestive of TB) but negative culture results overseas; or as having latent TB infection (LTBI) diagnosed overseas. Among 2.1 million U.S.-bound immigrants and refugees screened for TB overseas during 2013-2016, 90,737 were identified as at risk for TB. We analyzed a national data set of these at-risk immigrants and refugees and calculated rates of TB disease for those who completed post-arrival evaluation.Results: Among 4,225 persons with recent completion of treatment for pulmonary TB disease overseas, 3,005 (71.1%) completed post-arrival evaluation within 1 year of arrival; of these, TB disease was diagnosed in 22 (732 cases/100,000 persons), including 4 sputum culture-positive cases (133 cases/100,000 persons), 13 sputum culture-negative cases (433 cases/100,000 persons), and 5 cases with no reported sputum-culture results (166 cases/100,000 persons). Among 55,938 with suspected TB disease but negative culture results overseas, 37,089 (66.3%) completed post-arrival evaluation; of these, TB disease was diagnosed in 597 (1,610 cases/100,000 persons), including 262 sputum culture-positive cases (706 cases/100,000 persons), 281 sputum culture-negative cases (758 cases/100,000 persons), and 54 cases with no reported sputum-culture results (146 cases/100,000 persons). Among 30,574 with LTBI diagnosed overseas, 18,466 (60.4%) completed post-arrival evaluation; of these, TB disease was diagnosed in 48 (260 cases/100,000 persons), including 11 sputum culture-positive cases (60 cases/100,000 persons), 22 sputum culture-negative cases (119 cases/100,000 persons), and 15 cases with no reported sputum-culture results (81 cases/100,000 persons). Of 21,714 persons for whom treatment for LTBI was recommended at post-arrival evaluation, 14,977 (69.0%) initiated treatment and 8,695 (40.0%) completed treatment.Conclusions: Post-arrival evaluation of at-risk immigrants and refugees can be highly effective. To optimize the yield and impact of this intervention, strategies are needed to improve completion rates of post-arrival evaluation and treatment for LTBI.

Expanding travel medicine in the 21st century to address the health needs of the world's migrants.

HIGHLIGHT: The body of knowledge needed to effectively practice travel medicine has expanded since the 1990s, as migrants begin to comprise an increasing proportion of the world's population. We describe the unique needs of migrants and provide resources available to migration health practitioners. As the number of the world's migrants grows, collaboration across disciplines is key to achieving high-quality migration health practices.

Seroprevalence of Histoplasmosis in Somali, Burmese, and Hmong Refugees Residing in Thailand and Kenya.

Histoplasmosis is known to be endemic to the Midwestern United States, but cases have been reported throughout much of the world. Somali, Hmong, and Burmese (ethnically Karen) persons make up some of the largest refugee populations coming the United States in recent years. Yet, information about risk of Histoplasma capsulatum infection amongst these populations is limited. This study used the CDC Migrant Serum Bank to test ~100 samples from each of Somali, Burmese, and Hmong U.S.-bound refugees. Samples were tested by enzyme immunoassay for Histoplasma capsulatum IgG. Overall 1% (2/299) of refugee serum samples were positive for H. capsulatum IgG. One of 99 samples obtained from Hmong refugees was positive, and the other positive sample came from among 100 Burmese refugee samples. H capsulatum IgG positivity was detected at low levels in Hmong and Burmese refugees. No IgG positivity was detected among 100 Somali refugees.

Collection of Data on Race, Ethnicity, Language, and Nativity by US Public Health Surveillance and Monitoring Systems: Gaps and Opportunities.

OBJECTIVE: Despite increasing diversity in the US population, substantial gaps in collecting data on race, ethnicity, primary language, and nativity indicators persist in public health surveillance and monitoring systems. In addition, few systems provide questionnaires in foreign languages for inclusion of non-English speakers. We assessed (1) the extent of data collected on race, ethnicity, primary language, and nativity indicators (ie, place of birth, immigration status, and years in the United States) and (2) the use of data-collection instruments in non-English languages among Centers for Disease Control and Prevention (CDC)-supported public health surveillance and monitoring systems in the United States. METHODS: We identified CDC-supported surveillance and health monitoring systems in place from 2010 through 2013 by searching CDC websites and other federal websites. For each system, we assessed its website, documentation, and publications for evidence of the variables of interest and use of data-collection instruments in non-English languages. We requested missing information from CDC program officials, as needed. RESULTS: Of 125 data systems, 100 (80%) collected data on race and ethnicity, 2 more collected data on ethnicity but not race, 26 (21%) collected data on racial/ethnic subcategories, 40 (32%) collected data on place of birth, 21 (17%) collected data on years in the United States, 14 (11%) collected data on immigration status, 13 (10%) collected data on primary language, and 29 (23%) used non-English data-collection instruments. Population-based surveys and disease registries more often collected data on detailed variables than did case-based, administrative, and multiple-source systems. CONCLUSIONS: More complete and accurate data on race, ethnicity, primary language, and nativity can improve the quality, representativeness, and usefulness of public health surveillance and monitoring systems to plan and evaluate targeted public health interventions to eliminate health disparities.

Addressing a Yellow Fever Vaccine Shortage - United States, 2016-2017.

Recent manufacturing problems resulted in a shortage of the only U.S.-licensed yellow fever vaccine. This shortage is expected to lead to a complete depletion of yellow fever vaccine available for the immunization of U.S. travelers by mid-2017. CDC, the Food and Drug Administration (FDA), and Sanofi Pasteur are collaborating to ensure a continuous yellow fever vaccine supply in the United States. As part of this collaboration, Sanofi Pasteur submitted an expanded access investigational new drug (eIND) application to FDA in September 2016 to allow for the importation and use of an alternative yellow fever vaccine manufactured by Sanofi Pasteur France, with safety and efficacy comparable to the U.S.-licensed vaccine; the eIND was accepted by FDA in October 2016. The implementation of this eIND protocol included developing a systematic process for selecting a limited number of clinic sites to provide the vaccine. CDC and Sanofi Pasteur will continue to communicate with the public and other stakeholders, and CDC will provide a list of locations that will be administering the replacement vaccine at a later date.

Travel-Associated Zika Virus Disease Acquired in the Americas Through February 2016: A GeoSentinel Analysis.

Background: Zika virus has spread rapidly in the Americas and has been imported into many nonendemic countries by travelers. Objective: To describe clinical manifestations and epidemiology of Zika virus disease in travelers exposed in the Americas. Design: Descriptive, using GeoSentinel records. Setting: 63 travel and tropical medicine clinics in 30 countries. Patients: Ill returned travelers with a confirmed, probable, or clinically suspected diagnosis of Zika virus disease seen between January 2013 and 29 February 2016. Measurements: Frequencies of demographic, trip, and clinical characteristics and complications. Results: Starting in May 2015, 93 cases of Zika virus disease were reported. Common symptoms included exanthema (88%), fever (76%), and arthralgia (72%). Fifty-nine percent of patients were exposed in South America; 71% were diagnosed in Europe. Case status was established most commonly by polymerase chain reaction (PCR) testing of blood and less often by PCR testing of other body fluids or serology and plaque-reduction neutralization testing. Two patients developed Guillain-Barré syndrome, and 3 of 4 pregnancies had adverse outcomes (microcephaly, major fetal neurologic abnormalities, and intrauterine fetal death). Limitation: Surveillance data collected by specialized clinics may not be representative of all ill returned travelers, and denominator data are unavailable. Conclusion: These surveillance data help characterize the clinical manifestations and adverse outcomes of Zika virus disease among travelers infected in the Americas and show a need for global standardization of diagnostic testing. The serious fetal complications observed in this study highlight the importance of travel advisories and prevention measures for pregnant women and their partners. Travelers are sentinels for global Zika virus circulation and may facilitate further transmission. Primary Funding Source: Centers for Disease Control and Prevention, International Society of Travel Medicine, and Public Health Agency of Canada.

Partnerships that Facilitate a Refugee's Journey to Wellbeing.

The current global refugee crisis involves 65.3 million persons who have been displaced from their homes or countries of origin. While escaping immediate harm may be their first priority, displaced people go on to face numerous health risks, including trauma and injuries, malnutrition, infectious diseases, exacerbation of existing chronic diseases, and mental health conditions. This crisis highlights the importance of building capacity among health-care providers, scientists, and laboratorians to understand and respond to the health needs of refugees. The November 2016 American Society of Tropical Medicine and Hygiene (ASTMH) conference in Atlanta will feature an interactive exhibit entitled "The Refugee Journey to Wellbeing" and three symposia about refugee health. The symposia will focus on tropical disease challenges in refugee populations, careers in refugee health, and recent experiences of governmental agencies and nongovernmental organizations in responding to the global refugee crisis. We invite ASTMH attendees to attend the exhibit and symposia and consider contributions they could make to improve refugee health through tropical disease research or clinical endeavors.

Notes from the Field: Splenomegaly of Unknown Etiology in Congolese Refugees Applying for Resettlement to the United States - Uganda, 2015.

Approximately 70,000-90,000 refugees are resettled to the United States each year, and during the next 5 years, 50,000 Congolese refugees are expected to arrive in the United States. The International Organization for Migration (IOM) performs refugee medical examinations overseas for the U.S. Refugee Resettlement Program. In 2014, IOM reported that a large number of U.S.-bound Congolese refugees from Uganda had spleens that were enlarged on examination. During two evaluations of refugee populations in western Uganda in March and July 2015, refugees with splenomegaly on physical examination were offered additional assessment and treatment, including abdominal ultrasonography and laboratory testing. Among 987 persons screened, 145 (14.7%) had splenomegaly and received further testing. Among the 145 patients with splenomegaly, 63.4% were aged 5-17 years (median = 14.8 years). There was some evidence of family clustering, with 33 (22.7%) of the 145 cases occurring in families.

Estimation of Severe Middle East Respiratory Syndrome Cases in the Middle East, 2012-2016.

Using data from travelers to 4 countries in the Middle East, we estimated 3,250 (95% CI 1,300-6,600) severe cases of Middle East respiratory syndrome occurred in this region during September 2012-January 2016. This number is 2.3-fold higher than the number of laboratory-confirmed cases recorded in these countries.