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Imported Lassa fever, Pennsylvania, USA, 2010.

Lassa 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 nonspecific, 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, five 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 identified 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 Cote 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 floor. 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[degrees]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/16/10/1598appT.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 identified by real-time PCR by using samples collected 2 days earlier, and sequencing of the amplified fragment yielded a unique sequence similar to sequences from previous Lassa virus isolates from Liberia. Subsequent samples confirmed 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.

A contact investigation was undertaken by the hospital and local, state, federal, and international health agencies. Exposed persons were identified as any persons who potentially came into contact with the patient or his body fluids during his illness. Because no contacts had direct exposure to body fluids (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 fluids) were identified 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 identified.

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 first 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 fluids 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 nonspecific 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 notified, and specimens should be sent for specific diagnostic testing.

DOI: 10.3201/eid1610.100774

Acknowledgments

We thank medical staff, local and state public health personnel, and the staff of the Centers for Disease Control and Prevention who assisted with this investigation.

References

(1.) McCormick JB, King IJ, Webb PA, Johnson KM, O'Sullivan R, Smith ES, et al. A case-control study of the clinical diagnosis and course of Lassa fever. J Infect Dis. 1987;155:445-55.

(2.) McCormick JB, Webb PA, Krebs JW, Johnson KM, Smith ES. A prospective study of the epidemiology and ecology of Lassa fever. J Infect Dis. 1987;155:437-44.

(3.) Monath TP, Newhouse VF, Kemp GE, Setzer HW, Cacciapuoti A. Lassa virus isolation from Mastomys natalensis rodents during an epidemic in Sierra Leone. Science. 1974;185:263-5. DOI: 10.1126/ science.185.4147.263

(4.) Carey DE, Kemp GE, White HA, Pinneo L, Addy RF, Fom AL, et al. Lassa fever. Epidemiological aspects of the 1970 epidemic, Jos, Nigeria. Trans R Soc Trop Med Hyg. 1972;66:402-8. DOI: 10.1016/0035-9203(72)90271-4

(5.) Monath TP, Mertens PE, Patton R, Moser CR, Baum JJ, Pinneo L, et al. A hospital epidemic of Lassa fever in Zorzor, Liberia, March-April 1972. Am J Trop Med Hyg. 1973;22:773-9.

(6.) Frame JD. Clinical features of Lassa fever in Liberia. Rev Infect Dis. 1989;11(Suppl 4):S783-9.

(7.) Frame JD, Baldwin JM Jr, Gocke DJ, Troup JM. Lassa fever, a new virus disease of man from West Africa. I. Clinical description and pathological findings. Am J Trop Med Hyg. 1970;19:670-6.

(8.) Zweighaft RM, Fraser DW, Hattwick MA, Winkler WG, Jordan WC, Alter M, et al. Lassa fever: response to an imported case. N Engl J Med. 1977;297:803-7. DOI: 10.1056/NEJM197710132971504

(9.) Macher AM, Wolfe MS. Historical Lassa fever reports and 30-year clinical update. Emerg Infect Dis. 2006;12:835-7.

(10.) Holmes GP, McCormick JB, Trock SC, Chase RA, Lewis SM, Mason CA, et al. Lassa fever in the United States: investigation of a case and new guidelines for management. N Engl J Med. 1990;323:1120-3. DOI: 10.1056/NEJM199010183231607

(11.) Centers for Disease Control and Prevention. Imported Lassa fever--New Jersey, 2004. MMWR Morb Mortal Wkly Rep. 2004;53:894-7.

(12.) McCormick JB, King IJ, Webb PA, Scribner CL, Craven RB, Johnson KM, et al. Lassa fever: effective therapy with ribavirin. N Engl J Med. 1986;314:20-6. DOI: 10.1056/NEJM198601023140104

(13.) Centers for Disease Control and Prevention. Update: management of patients with suspected viral hemorrhagic fever--United States. MMWR Morb Mortal Wkly Rep. 1995;44:475-9.

(14.) Helmick CG, Webb PA, Scribner CL, Krebs JW, McCormick JB. No evidence for increased risk of Lassa fever infection in hospital staff. Lancet. 1986;328:1202-5. DOI: 10.1016/S0140-6736(86)92206-3

Author affiliations: University of Pennsylvania, Philadelphia, Pennsylvania, USA (V. Amorosa, R. McConnell, K.E. Dillon, K. Hamilton); Philadelphia Veterans Affairs Medical Center, Philadelphia (V. Amorosa); Centers for Disease Control and Prevention, Atlanta, Georgia, USA (A. MacNeil, A. Patel, B.R. Erickson, S. Campbell, B. Knust, D. Cannon, D. Miller, C. Manning, P.E. Rollin, S.T. Nichol); and Philadelphia Department of Health, Philadelphia (A. Patel)

Address for correspondence: Valerianna Amorosa, Philadelphia VAMCMedicine, University and Woodlawn, Philadelphia, PA 19104, USA; email: valerianna.amorosa@uphs.upenn.edu

Dr Amorosa is assistant professor of clinical medicine at the University of Pennsylvania and chief of infectious diseases at the Philadelphia Veterans Affairs Medical Center. Her research interests include HIV/hepatitis C co-infection.
Table. Day by day symptoms and clinical information for a man 47 years
of age with Lassa fever, Pennsylvania, USA, 2010*

                                                      Examination
Date                       Symptoms                    findings

Jan 13-17      Fevers and chills, sore throat,            NA
                arthralgias, diffuse abdominal
                             pain

Jan 18         Fevers and chills, sore throat,    Prominent parotids,
                   watery diarrhea, diffuse       posterior cervical
                       abdominal pain.             lymphadenopathy,
                                                   slight spleen tip

Jan 19         Fevers and chills, sore throat,     Slight tonsillar
                  substernal chest pain with       exudates, slight
                  inspiration and when lying          spleen tip
                  supine, diarrhea, diffuse
                 abdominal pain. Arthralgias
                           resolve.

Jan 20         Fevers and chills; sore throat;     Slight tonsillar
                 substernal chest pain, worse      exudates, slight
                  when lying down; diarrhea.          spleen tip
                  Abdominal pain improving.

Jan 21         Fevers and chills, sore throat,     Slight spleen tip
                diarrhea. Chest pain resolves.
                  Abdominal pain improving.

Jan 22         Fevers and chills, sore throat.         Prominent
                 Diarrhea resolves. Abdominal     sternocleidomastoid
                        pain resolves.                  muscles

Jan 23          Fevers and chills, sore throat         Prominent
                                                  sternocleidomastoid
                                                        muscles

Jan 24          Fevers and chills, sore throat         Prominent
                                                  sternocleidomastoid
                                                        muscles

Jan 25          Fevers and chills. Sore throat         Prominent
                          improves.               sternocleidomastoid
                                                        muscles

Jan 26          Fevers and chills. Sore throat    Neck less prominent
                          improves.

                Fevers and chills. Sore throat
Jan 27                    resolves.                Decreased parotid
                                                    enlargement and
                                                    lymphadenopathy
                      Fevers and chills
Jan 28-29
                        Fever resolves
Jan 30-Feb 3

                   Dowel
Date             movements         Clinical information

Jan 13-17            NA                     NA

Jan 18               12

Jan 19         [approximately      Tests for Clostridium
                equal to] 18    difficile, cryptosporidium,
                                  Giardia spp., thick and
                                   thin blood smears for
                                   malaria, Epstein-Barr
                                  virus, and respiratory
                                 virus panel; all negative

Jan 20               3                 HIV negative

Jan 21               5            Stool culture negative

Jan 22               NA             Stopped IV fluids.

Jan 23           3, formed        PCR positive for Lassa
                                           virus

Jan 24               NA

Jan 25           3, formed

Jan 26               NA

Jan 27               NA

Jan 28-29            NA

Jan 30-Feb 3         NA

Date             Clinical action

Jan 13-17               NA

Jan 18          Contact isolation
                     ordered.

Jan 19               Contact
                precautions. Blood
               samples to test for
                Lassa virus drawn.

Jan 20              EKG done,
               ribavirin requested,
                     airborne
                   precautions

Jan 21             Held off on
                  ribavirin. CDC
                received specimen.

Jan 22

Jan 23

Jan 24

Jan 25

Jan 26

Jan 27

Jan 28-29

Jan 30-Feb 3

* NA, not available; EKG, electrocardiogram; IV, intravenous; CDC,
Centers for Disease Control and Prevention.
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Article Details
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Title Annotation:DISPATCHES
Author:Amorosa, Valerianna; MacNeil, Adam; McConnell, Ryan; Patel, Ami; Dillon, Katherine E.; Hamilton, Kei
Publication:Emerging Infectious Diseases
Article Type:Disease/Disorder overview
Date:Oct 1, 2010
Words:2187
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