Investigation and Results

After confirming Seoul virus infection in the Wisconsin patients, CDC and WDHS initiated investigations into rat shipments to (trace-back) and from (trace-forward) the rattery to identify suspected and confirmed facilities. Trace-back investigations initially extended back 2 months prior to onset of clinical disease, based on the known maximum incubation period for Seoul virus in humans. As additional confirmed facilities were identified, tracing focused instead on interactions with known infected facilities, sometimes as much as 1 year prior. Suspected facilities included ratteries, homes, or pet stores that sold rats to a confirmed facility (a facility where at least one human or rat tested positive for Seoul virus infection) or housed rats that lived at or comingled with rats from a confirmed facility. Once a suspected facility was identified, local or state health officials interviewed persons with a history of rodent contact associated with the facility about their rat exposure and health history. Additionally, the primary rodent caretaker was interviewed using a standardized questionnaire to identify movement of rats into and out of the facility, including dates and locations where the rats were obtained. Local or state health officials offered laboratory testing for Seoul virus infection to all persons with rodent contact. Officials recommended testing for persons with a history of febrile illness and exposure to rats from a confirmed facility and for rats at suspected and confirmed facilities. Trace-forward and trace-back investigations of rat shipments at confirmed facilities identified additional suspected facilities, which were similarly assessed.

A suspected human case of Seoul virus infection was defined as a febrile illness (recorded temperature >101°F [38.3°C] or subjective history of fever) or an illness clinically compatible with Seoul virus infection (myalgia, headache, renal failure, conjunctival redness, thrombocytopenia, or proteinuria) without laboratory confirmation in a person reporting contact with rats from a confirmed or suspected facility. Human Seoul virus infections were laboratory-confirmed by detection of Seoul virus-specific immunoglobulin M (IgM) and/or immunoglobulin G (IgG) (6) antibodies by enzyme-linked immunosorbent assay (ELISA). In the United States, Seoul virus infections in rats were confirmed through detection of viral RNA by reverse transcription–polymerase chain reaction (RT-PCR) and/or IgG ELISA at CDC, or by CDC-validated commercial IgG testing. In Canada, public health officials investigated rat breeding facilities that exported rats to and imported rats from affected U.S. facilities. Seoul virus infection was detected in Canadian rats from breeding facilities using the same serologic and molecular-based protocols described for United States facilities.

By March 16, 2017, trace-forward and trace-back investigations identified approximately 100 suspected facilities in 21 states. Among these, 31 facilities in 11 states* had laboratory-confirmed human or rat infections, including a previously reported household in Tennessee with two confirmed human infections (1). Six confirmed facilities in six states (Georgia, Illinois, Missouri, South Carolina, Tennessee, and Utah) reported exchanging rats with Canadian ratteries during their trace-forward and trace-back investigations. A total of 163 persons in the United States and 20 in Canada consented to serologic testing; 17 (10.4%) U.S. residents and one (5.0%) Canadian resident had detectable IgM and IgG antibodies, indicating recent infection, and four (2.5%) U.S. residents and two (10.0%) Canadian residents had only IgG antibodies, indicating past or convalescent infection. Among the 17 U.S. patients with recent Seoul virus infection, eight reported recent febrile illness. Three were hospitalized, but did not develop HFRS, and all recovered. Serious illness was not reported in any Canadian patients. All strains detected in Canada and the United States were indistinguishable from one another based on nucleotide sequencing (7), indicating that a single strain was responsible for the outbreak. No single facility was identified as the origin of the outbreak.

Public Health Response

On January 24, CDC issued a Health Alert Notice to notify health departments and health care providers of the Seoul virus investigations.^† On February 20, the World Health Organization was notified of the U.S. and Canadian infections and investigations as required by International Health Regulations.^§ On January 31 and May 9, 2017, CDC and the Pet Industry Joint Advisory Council hosted calls to provide updates on the Seoul virus outbreak and to answer questions for the pet industry and fancy rat community. CDC created a website with Seoul virus facts and frequently asked questions for the public.

Health departments notified suspected and confirmed facilities and placed those facilities under quarantine, allowing no rats to enter or leave. Rat contact was limited to as few persons as possible to reduce transmission. In suspected facilities, CDC recommended rat testing be performed under the supervision of a public health official or licensed veterinarian. The quarantine was lifted when at least 4 weeks had elapsed since the newest animal was introduced, and all rats subsequently tested negative. Rats belonging to owners who refused to test their animals could remain quarantined for life or be euthanized. CDC recommended euthanasia of all rats in confirmed facilities as the most effective method to prevent transmission, although control recommendations differed by state and country according to local policies and response capacities. If euthanasia was not possible, then owners could either quarantine all rats for life or pursue quarantine with testing and culling. The testing and culling strategy entailed testing all rats and euthanizing only infected rats. Testing and euthanasia were repeated at 4 week intervals until all rats tested negative and the quarantine was lifted. In Canada, public health officials opted for education and a voluntary testing and culling approach to control Seoul virus transmission.

Discussion

This outbreak report, in parallel to the previously described investigation in Tennessee (1), describes the first known cases of Seoul virus infection in humans attributable to contact with pet rats in the United States and Canada. Human hantavirus infections are nationally notifiable in the United States and suspected cases should be reported to state or local health departments. Health care providers should consider Seoul virus infection in patients with febrile illness who report rat exposure; CDC recommends testing for any person with compatible illness and rodent contact. Testing is available at CDC^¶ and through some state and commercial laboratories. In Canada, testing is available for symptomatic persons with rat exposure, rattery owners associated with this investigation, and their rats through public health laboratories; for individually owned pet rats and ratteries not associated with the investigation, testing is available through a commercial laboratory.

Pet rat owners should be aware of the potential for Seoul virus infection. To keep themselves and their pets healthy, all persons with rodent contact should avoid bites or scratches and practice good hand hygiene, especially children and persons with compromised immune systems (2). CDC recommends hand washing after caring for rodents and before eating, drinking, or preparing food (2). If a pet rat is suspected of having Seoul virus, the person cleaning the rodent environment should wear a respirator, gloves, and cover any scratches or open wounds (8). An adult should routinely disinfect rat cages and accessories, including used bedding, with a 10% bleach solution or a commercial disinfectant (8). More information about rodent contact and disease prevention is available from CDC (8,9).

Rattery owners are encouraged to quarantine any newly acquired rats for 4 weeks and to test these rats for Seoul virus antibodies before allowing them to comingle with other rats. Commercial laboratories can perform Seoul virus testing of rodent blood samples, and comparisons of results from shared samples have been concordant with CDC’s ELISA and RT-PCR assays. To prevent transmission to humans, CDC recommends euthanasia of all rats in facilities with human or rat Seoul virus infections. Further guidance on methods to eradicate Seoul virus from infected ratteries should be obtained from local or state health departments.

References

1. Fill MA, Mullins H, May AS, et al. Notes from the field: multiple cases of Seoul virus infection in a household with infected pet rats—Tennessee, December 2016–April 2017. MMWR Morb Mortal Wkly Rep 2017;66:1081–2. CrossRef PubMed
2. CDC. Key messages about pet rodents. Atlanta, GA: US Department of Health and Human Services, CDC; 2017. https://www.cdc.gov/healthypets/pets/small-mammals/petrodents.html
3. Childs JE, Korch GW, Smith GA, Terry AD, Leduc JW. Geographical distribution and age related prevalence of antibody to Hantaan-like virus in rat populations of Baltimore, Maryland, USA. Am J Trop Med Hyg 1985;34:385–7. CrossRef PubMed
4. Knust B, Rollin PE. Twenty-year summary of surveillance for human hantavirus infections, United States. Emerg Infect Dis 2013;19:1934–7 . CrossRef PubMed
5. Jameson LJ, Taori SK, Atkinson B, et al. Pet rats as a source of hantavirus in England and Wales, 2013. Euro Surveill 2013;18:20415. PubMed
6. Ksiazek TG, West CP, Rollin PE, Jahrling PB, Peters CJ. ELISA for the detection of antibodies to Ebola viruses. J Infect Dis 1999;179(Suppl 1):S192–8. CrossRef PubMed
7. Woods C, Palekar R, Kim P, et al. Domestically acquired Seoul virus causing hemorrhagic fever with renal syndrome—Maryland, 2008. Clin Infect Dis 2009;49:e109–12. CrossRef PubMed
8. CDC. Cleaning up after pet rodents to reduce the risk of Seoul virus infection. Atlanta, GA: US Department of Health and Human Services, CDC; 2017. https://www.cdc.gov/hantavirus/outbreaks/seoul-virus/cleaning-up-pet-rodents.html
9. CDC. Healthy pets healthy people. Atlanta, GA: US Department of Health and Human Services, CDC; 2017. https://www.cdc.gov/healthypets/