Imported Lassa Fever, Pennsylvania, USA, 2010

We report a case of Lassa fever in a US traveler who visited rural Liberia, became ill while in country, sought medical care upon return to the United States, and subsequently had his illness laboratory confirmed. The patient recovered with supportive therapy. No secondary cases occurred.

L assa fever is a potentially severe viral infection caused by Lassa virus (family Arenaviridae, genus Arenavirus), with an overall case-fatality rate of 1%-2% and a case-fatality rate of 15%-20% for hospitalized patients (1,2). The virus is endemic to West Africa, with the reservoir host being Mastomys spp. rodents (3). Person-to-person transmission of Lassa virus can occur through direct exposure to infected blood or secretions, and instances of nosocomial transmission have been documented (4,5). Primary symptoms of Lassa fever are fever, headache, nausea, diarrhea, sore throat, and myalgia; hemorrhagic signs or deafness may also occur during illness (1,6).
Because the incubation period ranges from a few days to >2 weeks (1,5) and many symptoms are nonspecifi c, the potential exists for human carriage of Lassa virus to areas outside those to which it is endemic, putting travel companions, close contacts, and healthcare providers at risk for secondary infection. Before 2010, fi ve instances of imported Lassa virus were recorded in persons from West Africa to the United States. Although early instances involved sick persons who were airlifted to the United States for diagnosis and treatment (7-9), the 2 most recent occurrences (1989 and 2004) involved persons who were not identifi ed as potentially infectious until healthcare was sought in the United States (10,11). Here we report a case in a person who became infected and sick during a trip to Liberia and sought care upon return to the United States.

The Case
A Liberian man 47 years of age living in the United States traveled to Liberia in January 2010. He arrived in Monrovia, then spent 5 days traveling throughout Nimba County in north-central Liberia, bordering Guinea and Côte d'Ivoire. He reported sleeping nightly in his rural native village in a dwelling infested with rats and recalled several rat carcasses on the bedroom fl oor. On the day of his departure from Liberia, he developed fever, chills, joint pain of the knees and ankles, anorexia, sore throat, diffuse skin tenderness, and mild shortness of breath; he began taking amoxicillin and chloroquine before departing Liberia.
The patient's symptoms persisted upon arrival in the United States, prompting him to seek medical attention on day 5 of his illness. When he sought treatment, he had fever of 103°F, pulse of 99 beats/min, respiratory rate of 15 breaths/min, and blood pressure of 120/80 mm Hg (online Appendix Table, www.cdc.gov/EID/content/16/10/1598-appT.htm). His physical examination was notable for posterior cervical adenopathy and a palpable spleen tip (Table). He had no evidence of conjunctival, nasal, or oral petechiae; no skin rashes; and no signs of hemorrhage or other lesions. Initial laboratory data showed leukopenia and thrombocytopenia and minimal transaminase elevations (online Appendix Table). Empiric malaria treatment was initiated upon admission and was subsequently discontinued when Plasmodium spp. antigen testing was negative and thick and thin blood smears showed no evident parasitemia. By the next day, mild pharyngitis with slight tonsillar exudates had developed. On the third hospital day, substernal chest pain and profuse watery diarrhea developed. Increasing transaminases and a slight coagulopathy were noted. Lassa fever was considered in the differential diagnosis; contact precautions and, subsequently, airborne precautions were taken. Because of noted clinical improvement, he was not given empiric intravenous ribavirin.
On day 5 of hospitalization, Lassa virus was identifi ed by real-time PCR by using samples collected 2 days earlier, and sequencing of the amplifi ed fragment yielded a unique sequence similar to sequences from previous Lassa virus isolates from Liberia. Subsequent samples confi rmed Lassa fever diagnosis on the basis of real-time PCR, viral culture, and serology (Table).
The patient's fever resolved by day 16 of his illness. After 2 successive negative blood real-time PCR results, he was discharged from the hospital on day 21 of his illness with instructions to avoid unprotected sexual intercourse for 2 months. No hearing abnormalities were noted at the time of discharge or during telephone conversations 2 weeks and 2 months later.

Imported Lassa Fever
A contact investigation was undertaken by the hospital and local, state, federal, and international health agencies. Exposed persons were identifi ed as any persons who potentially came into contact with the patient or his body fl uids during his illness. Because no contacts had direct exposure to body fl uids (other than the patient's wife in Africa with whom he had sexual intercourse before becoming ill and who remained well, according to telephone follow-up with the patient), no patient contacts were considered high risk for secondary transmission (10). In total, 140 persons, including the patient's family in the United States, co-workers, and hospital workers who had contact with him (but did not have direct contact with bodily fl uids) were identifi ed as low-risk contacts. Health communication materials were developed on the basis of previous Lassa fever contact tracing activities (10). All hospital and community contacts were provided a Lassa fever fact sheet and asked to seek medical consultation if fever or other signs and symptoms of Lassa fever appeared. Upon completion of 21 days of follow-up, no secondary cases were identifi ed.

Conclusions
The spectrum of Lassa fever can run from asymptomatic seroconversion to severe hemorrhagic fever with multiple organ failure and death (1,2,6). Factors supporting the diagnosis of Lassa fever in returning travelers include relevant epidemiologic exposure (travel to rural West Africa), signs and symptoms consistent with Lassa fever, and the absence of other infectious agents that can account for the illness. Although this patient did not seek treatment for hemorrhagic signs, his fever, pharyngitis, chest pain, and diarrhea (1,6), as well as thrombocytopenia and elevated transaminases, were consistent with Lassa fever (6,12). Early institution of ribavirin can dramatically decrease  death rates among patients with severe Lassa fever if given within the fi rst 6 days of illness (12); therefore, empiric ribavirin should be considered for an ill patient suspected of having Lassa fever. As in this case, early suspicion of Lassa fever should prompt isolation measures to avoid secondary transmission; laboratory testing should be limited to essential tests, and all laboratory specimens should be handled with appropriate biosafety precautions to avoid aerosolizing the virus (13). Experience in regions where Lassa virus is endemic suggests human-to-human transmission occurs through direct contact with blood and body fl uids or large-particle inhalation; transmission through viral aerosolization is not seen; and generally, when universal precautions are undertaken, transmission is unlikely (14). Nonetheless, aerosol in addition to contact precautions were undertaken once Lassa fever was suspected, given the theoretical potential for acquiring infection through inhalation of airborne virus from respiratory secretions or, in this case, copious diarrhea.
The patient described in this report represents the sixth known occurrence of Lassa fever imported to the United States. Clinicians treating recent travelers to West Africa who are febrile should obtain detailed histories from patients to determine whether they have traveled into rural areas in which the potential for exposure to rodents exists. The symptoms, signs, and laboratory abnormalities of Lassa fever are nonspecifi c and can overlap with other tropical infections. Therefore, efforts should be made to promptly diagnose or rule out other infectious agents in a patient who has the appropriate travel and exposure history so that further diagnostic studies and empiric therapy with ribavirin can be undertaken rapidly. Moreover, as soon as Lassa fever is suspected, patients and their specimens should be handled with adequate precautions, the local health department and Centers for Disease Control and Prevention should be notifi ed, and specimens should be sent for specifi c diagnostic testing.