Outbreak of Mycobacterium orygis in a Shipment of Cynomolgus Macaques Imported from Southeast Asia - United States, February-May 2023.

Nonhuman primates (NHP) can become infected with the same species of Mycobacteria that cause human tuberculosis. All NHP imported into the United States are quarantined and screened for tuberculosis; no confirmed cases of tuberculosis were diagnosed among NHP during CDC-mandated quarantine during 2013-2020. In February 2023, an outbreak of tuberculosis caused by Mycobacterium orygis was detected in a group of 540 cynomolgus macaques (Macaca fascicularis) imported to the United States from Southeast Asia for research purposes. Although the initial exposure to M. orygis is believed to have occurred before the macaques arrived in the United States, infected macaques were first detected during CDC-mandated quarantine. CDC collaborated with the importer and U.S. Department of Agriculture's National Veterinary Services Laboratories in the investigation and public health response. A total of 26 macaques received positive test results for M. orygis by culture, but rigorous occupational safety protocols implemented during transport and at the quarantine facility prevented cases among caretakers in the United States. Although the zoonotic disease risk to the general population remains low, this outbreak underscores the importance of CDC's regulatory oversight of NHP importation and adherence to established biosafety protocols to protect the health of the United States research animal population and the persons who interact with them.

Contact Tracing for Mpox Clade II Cases Associated with Air Travel - United States, July 2021-August 2022.

Monkeypox virus (MPXV) can spread among humans through direct contact with lesions, scabs, or saliva; via respiratory secretions; and indirectly from fomites; via percutaneous injuries; and by crossing the placenta to the fetus during pregnancy. Since 2022, most patients with mpox in the United States have experienced painful skin lesions, and some have had severe illness. During 2021-2022, CDC initiated aircraft contact investigations after receiving reports of travelers on commercial flights with probable or confirmed mpox during their infectious period. Data were collected 1) during 2021, when two isolated clade II mpox cases not linked to an outbreak were imported into the United States by international travelers and 2) for flights arriving in or traveling within the United States during April 30-August 2, 2022, after a global clade II mpox outbreak was detected in May 2022. A total of 113 persons (100 passengers and 13 crew members) traveled on 221 flights while they were infectious with mpox. CDC developed definitions for aircraft contacts based on proximity to mpox cases and flight duration, sent information about these contacts to U.S. health departments, and received outcome information for 1,046 (68%) of 1,538 contacts. No traveler was found to have acquired mpox via a U.S. flight exposure. For persons with mpox and their contacts who had departed from the United States, CDC forwarded contact information as well as details about the exposure event to destination countries to facilitate their own public health investigations. Findings from these aircraft contact investigations suggest that traveling on a flight with a person with mpox does not appear to constitute an exposure risk or warrant routine contact tracing activities. Nonetheless, CDC recommends that persons with mpox isolate and delay travel until they are no longer infectious.

SARS-CoV-2 Cases Reported on International Arriving and Domestic Flights: United States, January 2020-December 2021.

Objectives. To describe trends in the number of air travelers categorized as infectious with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2; the virus that causes COVID-19) in the context of total US COVID-19 vaccinations administered, and overall case counts of SARS-CoV-2 in the United States. Methods. We searched the Quarantine Activity Reporting System (QARS) database for travelers with inbound international or domestic air travel, a positive SARS-CoV-2 lab result, and a surveillance categorization of SARS-CoV-2 infection reported during January 2020 to December 2021. Travelers were categorized as infectious during travel if they had arrival dates from 2 days before to 10 days after symptom onset or a positive viral test. Results. We identified 80 715 persons meeting our inclusion criteria; 67 445 persons (83.6%) had at least 1 symptom reported. Of 67 445 symptomatic passengers, 43 884 (65.1%) reported an initial symptom onset date after their flight arrival date. The number of infectious travelers mirrored the overall number of US SARS-CoV-2 cases. Conclusions. Most travelers in the study were asymptomatic during travel, and therefore unknowingly traveled while infectious. During periods of high community transmission, it is important for travelers to stay up to date with COVID-19 vaccinations and consider wearing a high-quality mask to decrease the risk of transmission. (Am J Public Health. 2023;113(8):904-908. https://doi.org/10.2105/AJPH.2023.307325).

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.

Review of CDC's Suspension of and Advance Written Approval Process for Dogs Entering the United States from Egypt - May 2019-December 2020.

Dog-maintained rabies virus variant (DMRVV) was eliminated in the United States in 2007. During 2015­2019, three dogs with rabies were imported into the United States from Egypt, where DMRVV is endemic. CDC developed a risk mitigation strategy, in consultation with a diverse group of subject matter experts, that permitted 296 dogs to be imported from Egypt during May 10, 2019­December 31, 2020, minimizing the risk for future rabid dog importations. The broadly vetted risk mitigation strategy, which included serologic testing for rabies antibody titer, improved CDC's ability to ensure that imported dogs from Egypt posed no public health risk in the United States. This strategy could be used to guide future policy decisions regarding dog importations.

Rabies in a Dog Imported from Azerbaijan - Pennsylvania, 2021.

On June 16, 2021, rabies virus infection was confirmed in a dog included in a shipment of rescue animals imported into the United States from Azerbaijan. A multistate investigation was conducted to prevent secondary rabies cases, avoid reintroduction of a dog-maintained rabies virus variant (DMRVV), identify persons who might have been exposed and would be recommended to receive rabies postexposure prophylaxis, and investigate the cause of importation control failures. Results of a prospective serologic monitoring (PSM) protocol suggested that seven of 32 (22%) animals from the same shipment as the dog with confirmed rabies virus infection and who had available titer results after rabies vaccine booster had not been adequately vaccinated against rabies before importation. A requirement for rabies vaccination certificates alone will not adequately identify improper vaccination practices or fraudulent paperwork and are insufficient as a stand-alone rabies importation prevention measure. Serologic titers before importation would mitigate the risk for importing DMRVV.

Use of US Public Health Travel Restrictions during COVID-19 Outbreak on Diamond Princess Ship, Japan, February-April 2020.

Public health travel restrictions (PHTR) are crucial measures during communicable disease outbreaks to prevent transmission during commercial airline travel and mitigate cross-border importation and spread. We evaluated PHTR implementation for US citizens on the Diamond Princess during its coronavirus disease (COVID-19) outbreak in Japan in February 2020 to explore how PHTR reduced importation of COVID-19 to the United States during the early phase of disease containment. Using PHTR required substantial collaboration among the US Centers for Disease Control and Prevention, other US government agencies, the cruise line, and public health authorities in Japan. Original US PHTR removal criteria were modified to reflect international testing protocols and enable removal of PHTR for persons who recovered from illness. The impact of PHTR on epidemic trajectory depends on the risk for transmission during travel and geographic spread of disease. Lessons learned from the Diamond Princess outbreak provide critical information for future PHTR use.

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.

Severe Acute Respiratory Syndrome Coronavirus 2 Prevalence, Seroprevalence, and Exposure among Evacuees from Wuhan, China, 2020.

To determine prevalence of, seroprevalence of, and potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among a cohort of evacuees returning to the United States from Wuhan, China, in January 2020, we conducted a cross-sectional study of quarantined evacuees from 1 repatriation flight. Overall, 193 of 195 evacuees completed exposure surveys and submitted upper respiratory or serum specimens or both at arrival in the United States. Nearly all evacuees had taken preventive measures to limit potential exposure while in Wuhan, and none had detectable SARS-CoV-2 in upper respiratory tract specimens, suggesting the absence of asymptomatic respiratory shedding among this group at the time of testing. Evidence of antibodies to SARS-CoV-2 was detected in 1 evacuee, who reported experiencing no symptoms or high-risk exposures in the previous 2 months. These findings demonstrated that this group of evacuees posed a low risk of introducing SARS-CoV-2 to the United States.

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.

Public Health Responses to COVID-19 Outbreaks on Cruise Ships - Worldwide, February-March 2020.

An estimated 30 million passengers are transported on 272 cruise ships worldwide each year* (1). Cruise ships bring diverse populations into proximity for many days, facilitating transmission of respiratory illness (2). SARS-CoV-2, the virus that causes coronavirus disease (COVID-19) was first identified in Wuhan, China, in December 2019 and has since spread worldwide to at least 187 countries and territories. Widespread COVID-19 transmission on cruise ships has been reported as well (3). Passengers on certain cruise ship voyages might be aged ≥65 years, which places them at greater risk for severe consequences of SARS-CoV-2 infection (4). During February-March 2020, COVID-19 outbreaks associated with three cruise ship voyages have caused more than 800 laboratory-confirmed cases among passengers and crew, including 10 deaths. Transmission occurred across multiple voyages of several ships. This report describes public health responses to COVID-19 outbreaks on these ships. COVID-19 on cruise ships poses a risk for rapid spread of disease, causing outbreaks in a vulnerable population, and aggressive efforts are required to contain spread. All persons should defer all cruise travel worldwide during the COVID-19 pandemic.

Rabies in a Dog Imported from Egypt - Connecticut, 2017.

In 2007, the United States successfully eliminated canine rabies virus variant. Globally, however, dogs remain the principal source of human rabies infections. Since 2007, three cases of canine rabies virus variant were reported in dogs imported into the United States, one each from India (2007), Iraq (2008), and Egypt (2015) (1-3). On December 20, 2017, a dog imported into the United States from Egypt was identified with rabies, representing the second case from Egypt in 3 years. An Egyptian-based animal rescue organization delivered four dogs from Cairo, Egypt, to a flight parent (a person solicited through social media, often not affiliated with the rescue organization, and usually compensated with an airline ticket), who transported the dogs to the United States. The flight parent arrived at John F. Kennedy International Airport (JFK) in New York City and, via transporters (persons who shuttle dogs from one state to another), transferred the dogs to foster families; the dogs ultimately were adopted in three states. The Connecticut Department of Public Health Laboratory (CDPHL) confirmed the presence of a canine rabies virus variant in one of the dogs, a male aged 6 months that was adopted by a Connecticut family. An investigation revealed the possibility of falsified rabies vaccination documentation presented on entry at JFK, allowing the unvaccinated dog entry to the United States. This report highlights the continuing risk posed by the importation of dogs inadequately vaccinated against rabies from high-risk countries and the difficulties in verifying any imported dog's health status and rabies vaccination history.

Responding to Communicable Diseases in Internationally Mobile Populations at Points of Entry and along Porous Borders, Nigeria, Benin, and Togo.

Recent multinational disease outbreaks demonstrate the risk of disease spreading globally before public health systems can respond to an event. To ensure global health security, countries need robust multisectoral systems to rapidly detect and respond to domestic or imported communicable diseases. The US Centers for Disease Control and Prevention International Border Team works with the governments of Nigeria, Togo, and Benin, along with Pro-Health International and the Abidjan-Lagos Corridor Organization, to build sustainable International Health Regulations capacities at points of entry (POEs) and along border regions. Together, we strengthen comprehensive national and regional border health systems by developing public health emergency response plans for POEs, conducting qualitative assessments of public health preparedness and response capacities at ground crossings, integrating internationally mobile populations into national health surveillance systems, and formalizing cross-border public health coordination. Achieving comprehensive national and regional border health capacity, which advances overall global health security, necessitates multisectoral dedication to the aforementioned components.

Public health response to commercial airline travel of a person with Ebola virus infection - United States, 2014.

Before the current Ebola epidemic in West Africa, there were few documented cases of symptomatic Ebola patients traveling by commercial airline, and no evidence of transmission to passengers or crew members during airline travel. In July 2014 two persons with confirmed Ebola virus infection who were infected early in the Nigeria outbreak traveled by commercial airline while symptomatic, involving a total of four flights (two international flights and two Nigeria domestic flights). It is not clear what symptoms either of these two passengers experienced during flight; however, one collapsed in the airport shortly after landing, and the other was documented to have fever, vomiting, and diarrhea on the day the flight arrived. Neither infected passenger transmitted Ebola to other passengers or crew on these flights. In October 2014, another airline passenger, a U.S. health care worker who had traveled domestically on two commercial flights, was confirmed to have Ebola virus infection. Given that the time of onset of symptoms was uncertain, an Ebola airline contact investigation in the United States was conducted. In total, follow-up was conducted for 268 contacts in nine states, including all 247 passengers from both flights, 12 flight crew members, eight cleaning crew members, and one federal airport worker (81 of these contacts were documented in a report published previously). All contacts were accounted for by state and local jurisdictions and followed until completion of their 21-day incubation periods. No secondary cases of Ebola were identified in this investigation, confirming that transmission of Ebola during commercial air travel did not occur.

Analyzing GeoSentinel surveillance data: a comparison of methods to explore acute gastrointestinal illness among international travelers.

GeoSentinel is a global surveillance network of travel medicine clinics that collect data from ill international travelers. Analyses have relied on proportionate morbidity calculations, but proportionate morbidity cannot estimate disease risk because healthy travelers are not included in the denominator. The authors evaluated the use of a case-control design, controlling for GeoSentinel site and date of clinic visit, to calculate a reporting odds ratio (ROR). The association between region of travel and acute gastrointestinal illness was evaluated. All analyses found that the association with acute gastrointestinal illness was greatest among those who traveled to North Africa and South-Central Asia. There was consistency in the magnitude of the ROR and proportionate morbidity ratio (PMR) in regions such as the Caribbean. However, in other regions, the matched ROR was noticeably different than the PMR. The case-control ROR may be preferred for single-disease/syndrome analytical studies using GeoSentinel surveillance data or other surveillance data.

Acute muscular sarcocystosis: an international investigation among ill travelers returning from Tioman Island, Malaysia, 2011-2012.

BACKGROUND: Through 2 international traveler-focused surveillance networks (GeoSentinel and TropNet), we identified and investigated a large outbreak of acute muscular sarcocystosis (AMS), a rarely reported zoonosis caused by a protozoan parasite of the genus Sarcocystis, associated with travel to Tioman Island, Malaysia, during 2011-2012. METHODS: Clinicians reporting patients with suspected AMS to GeoSentinel submitted demographic, clinical, itinerary, and exposure data. We defined a probable case as travel to Tioman Island after 1 March 2011, eosinophilia (>5%), clinical or laboratory-supported myositis, and negative trichinellosis serology. Case confirmation required histologic observation of sarcocysts or isolation of Sarcocystis species DNA from muscle biopsy. RESULTS: Sixty-eight patients met the case definition (62 probable and 6 confirmed). All but 2 resided in Europe; all were tourists and traveled mostly during the summer months. The most frequent symptoms reported were myalgia (100%), fatigue (91%), fever (82%), headache (59%), and arthralgia (29%); onset clustered during 2 distinct periods: "early" during the second and "late" during the sixth week after departure from the island. Blood eosinophilia and elevated serum creatinine phosphokinase (CPK) levels were observed beginning during the fifth week after departure. Sarcocystis nesbitti DNA was recovered from 1 muscle biopsy. CONCLUSIONS: Clinicians evaluating travelers returning ill from Malaysia with myalgia, with or without fever, should consider AMS, noting the apparent biphasic aspect of the disease, the later onset of elevated CPK and eosinophilia, and the possibility for relapses. The exact source of infection among travelers to Tioman Island remains unclear but needs to be determined to prevent future illnesses.

Airport exit and entry screening for Ebola--August-November 10, 2014.

In response to the largest recognized Ebola virus disease epidemic now occurring in West Africa, the governments of affected countries, CDC, the World Health Organization (WHO), and other international organizations have collaborated to implement strategies to control spread of the virus. One strategy recommended by WHO calls for countries with Ebola transmission to screen all persons exiting the country for "unexplained febrile illness consistent with potential Ebola infection." Exit screening at points of departure is intended to reduce the likelihood of international spread of the virus. To initiate this strategy, CDC, WHO, and other global partners were invited by the ministries of health of Guinea, Liberia, and Sierra Leone to assist them in developing and implementing exit screening procedures. Since the program began in August 2014, an estimated 80,000 travelers, of whom approximately 12,000 were en route to the United States, have departed by air from the three countries with Ebola transmission. Procedures were implemented to deny boarding to ill travelers and persons who reported a high risk for exposure to Ebola; no international air traveler from these countries has been reported as symptomatic with Ebola during travel since these procedures were implemented.

First confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the United States, updated information on the epidemiology of MERS-CoV infection, and guidance for the public, clinicians, and public health authorities - May 2014.

Since mid-March 2014, the frequency with which cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection have been reported has increased, with the majority of recent cases reported from Saudi Arabia and United Arab Emirates (UAE). In addition, the frequency with which travel-associated MERS cases have been reported and the number of countries that have reported them to the World Health Organization (WHO) have also increased. The first case of MERS in the United States, identified in a traveler recently returned from Saudi Arabia, was reported to CDC by the Indiana State Department of Health on May 1, 2014, and confirmed by CDC on May 2. A second imported case of MERS in the United States, identified in a traveler from Saudi Arabia having no connection with the first case, was reported to CDC by the Florida Department of Health on May 11, 2014. The purpose of this report is to alert clinicians, health officials, and others to increase awareness of the need to consider MERS-CoV infection in persons who have recently traveled from countries in or near the Arabian Peninsula. This report summarizes recent epidemiologic information, provides preliminary descriptions of the cases reported from Indiana and Florida, and updates CDC guidance about patient evaluation, home care and isolation, specimen collection, and travel as of May 13, 2014.

Accurate whole human genome sequencing using reversible terminator chemistry.

DNA sequence information underpins genetic research, enabling discoveries of important biological or medical benefit. Sequencing projects have traditionally used long (400-800 base pair) reads, but the existence of reference sequences for the human and many other genomes makes it possible to develop new, fast approaches to re-sequencing, whereby shorter reads are compared to a reference to identify intraspecies genetic variation. Here we report an approach that generates several billion bases of accurate nucleotide sequence per experiment at low cost. Single molecules of DNA are attached to a flat surface, amplified in situ and used as templates for synthetic sequencing with fluorescent reversible terminator deoxyribonucleotides. Images of the surface are analysed to generate high-quality sequence. We demonstrate application of this approach to human genome sequencing on flow-sorted X chromosomes and then scale the approach to determine the genome sequence of a male Yoruba from Ibadan, Nigeria. We build an accurate consensus sequence from >30x average depth of paired 35-base reads. We characterize four million single-nucleotide polymorphisms and four hundred thousand structural variants, many of which were previously unknown. Our approach is effective for accurate, rapid and economical whole-genome re-sequencing and many other biomedical applications.