In a study of Lassa fever in Sierra Leone, West Africa, we identified two variables associated with a high risk of death, and we evaluated the efficacy of ribavirin and Lassa virus-convalescent plasma for the treatment of Lassa fever. A serum aspartate aminotransferase level greater than or equal to 150 IU per liter at the time of hospital admission was associated with a case-fatality rate of 55 percent (33 of 60). Patients with the same risk factor who were treated for 10 days with intravenous ribavirin, begun within the first 6 days after the onset of fever, had a case-fatality rate of 5 percent (1 of 20) (P = 0.0002 by Fisher's exact test). Patients whose treatment began seven or more days after the onset of fever had a case-fatality rate of 26 percent (11 of 43) (P = 0.01). Viremia with levels greater than or equal to 10(3.6) TCID50 per milliliter on admission was associated with a case-fatality rate of 76 percent (35 of 46). Patients with this risk factor who were treated with intravenous ribavirin within the first six days after onset of fever had a case-fatality rate of 9 percent (1 of 11) (P = 0.006), whereas those treated after seven days or more of illness had a fatality rate of 47 percent (9 of 19) (P = 0.035). Oral ribavirin was also effective in patients at high risk of death. Lassa-convalescent plasma did not significantly reduce mortality in any of the high-risk groups. We conclude that ribavirin is effective in the treatment of Lassa fever and that it should be used at any point in the illness, as well as for postexposure prophylaxis.
This article has been cited by other articles:
Baize, S., Marianneau, P., Loth, P., Reynard, S., Journeaux, A., Chevallier, M., Tordo, N., Deubel, V., Contamin, H.
(2009). Early and Strong Immune Responses Are Associated with Control of Viral Replication and Recovery in Lassa Virus-Infected Cynomolgus Monkeys. J. Virol.
83: 5890-5903
[Abstract][Full Text]
Bowick, G. C., Spratt, H. M., Hogg, A. E., Endsley, J. J., Wiktorowicz, J. E., Kurosky, A., Luxon, B. A., Gorenstein, D. G., Herzog, N. K.
(2009). Analysis of the Differential Host Cell Nuclear Proteome Induced by Attenuated and Virulent Hemorrhagic Arenavirus Infection. J. Virol.
83: 687-700
[Abstract][Full Text]
Larson, R. A., Dai, D., Hosack, V. T., Tan, Y., Bolken, T. C., Hruby, D. E., Amberg, S. M.
(2008). Identification of a Broad-Spectrum Arenavirus Entry Inhibitor. J. Virol.
82: 10768-10775
[Abstract][Full Text]
Hass, M., Lelke, M., Busch, C., Becker-Ziaja, B., Gunther, S.
(2008). Mutational Evidence for a Structural Model of the Lassa Virus RNA Polymerase Domain and Identification of Two Residues, Gly1394 and Asp1395, That Are Critical for Transcription but Not Replication of the Genome. J. Virol.
82: 10207-10217
[Abstract][Full Text]
Howe, A. Y. M., Cheng, H., Johann, S., Mullen, S., Chunduru, S. K., Young, D. C., Bard, J., Chopra, R., Krishnamurthy, G., Mansour, T., O'Connell, J.
(2008). Molecular Mechanism of Hepatitis C Virus Replicon Variants with Reduced Susceptibility to a Benzofuran Inhibitor, HCV-796. Antimicrob. Agents Chemother.
52: 3327-3338
[Abstract][Full Text]
Gowen, B. B., Wong, M.-H., Jung, K.-H., Sanders, A. B., Mendenhall, M., Bailey, K. W., Furuta, Y., Sidwell, R. W.
(2007). In Vitro and In Vivo Activities of T-705 against Arenavirus and Bunyavirus Infections. Antimicrob. Agents Chemother.
51: 3168-3176
[Abstract][Full Text]
Carrion, R. Jr., Brasky, K., Mansfield, K., Johnson, C., Gonzales, M., Ticer, A., Lukashevich, I., Tardif, S., Patterson, J.
(2007). Lassa Virus Infection in Experimentally Infected Marmosets: Liver Pathology and Immunophenotypic Alterations in Target Tissues. J. Virol.
81: 6482-6490
[Abstract][Full Text]
LIVONESI, M. C., DE SOUSA, R. L. M., BADRA, S. J., FIGUEIREDO, L. T.M.
(2006). IN VITRO AND IN VIVO STUDIES OF RIBAVIRIN ACTION ON BRAZILIAN ORTHOBUNYAVIRUS. Am J Trop Med Hyg
75: 1011-1016
[Abstract][Full Text]
Botten, J., Alexander, J., Pasquetto, V., Sidney, J., Barrowman, P., Ting, J., Peters, B., Southwood, S., Stewart, B., Rodriguez-Carreno, M. P., Mothe, B., Whitton, J. L., Sette, A., Buchmeier, M. J.
(2006). Identification of Protective Lassa Virus Epitopes That Are Restricted by HLA-A2.. J. Virol.
80: 8351-8361
[Abstract][Full Text]
Fischer, S. A., Graham, M. B., Kuehnert, M. J., Kotton, C. N., Srinivasan, A., Marty, F. M., Comer, J. A., Guarner, J., Paddock, C. D., DeMeo, D. L., Shieh, W.-J., Erickson, B. R., Bandy, U., DeMaria, A. Jr., Davis, J. P., Delmonico, F. L., Pavlin, B., Likos, A., Vincent, M. J., Sealy, T. K., Goldsmith, C. S., Jernigan, D. B., Rollin, P. E., Packard, M. M., Patel, M., Rowland, C., Helfand, R. F., Nichol, S. T., Fishman, J. A., Ksiazek, T., Zaki, S. R., the LCMV in Transplant Recipients Investigation Te,
(2006). Transmission of lymphocytic choriomeningitis virus by organ transplantation.. NEJM
354: 2235-2249
[Abstract][Full Text]
Georges-Courbot, M. C., Contamin, H., Faure, C., Loth, P., Baize, S., Leyssen, P., Neyts, J., Deubel, V.
(2006). Poly(I)-Poly(C12U) but Not Ribavirin Prevents Death in a Hamster Model of Nipah Virus Infection.. Antimicrob. Agents Chemother.
50: 1768-1772
[Abstract][Full Text]
Garcia, C. C., Djavani, M., Topisirovic, I., Borden, K. L. B., Salvato, M. S., Damonte, E. B.
(2006). Arenavirus Z protein as an antiviral target: virus inactivation and protein oligomerization by zinc finger-reactive compounds.. J. Gen. Virol.
87: 1217-1228
[Abstract][Full Text]
Boesen, A., Sundar, K., Coico, R.
(2005). Lassa Fever Virus Peptides Predicted by Computational Analysis Induce Epitope-Specific Cytotoxic-T-Lymphocyte Responses in HLA-A2.1 Transgenic Mice. CVI
12: 1223-1230
[Abstract][Full Text]
Gowen, B. B., Barnard, D. L., Smee, D. F., Wong, M.-H., Pace, A. M., Jung, K.-H., Winslow, S. G., Bailey, K. W., Blatt, L. M., Sidwell, R. W.
(2005). Interferon Alfacon-1 Protects Hamsters from Lethal Pichinde Virus Infection. Antimicrob. Agents Chemother.
49: 2378-2386
[Abstract][Full Text]
Yip, T. T.C., Chan, J. W.M., Cho, W. C.S., Yip, T.-T., Wang, Z., Kwan, T.-L., Law, S. C.K., Tsang, D. N.C., Chan, J. K.C., Lee, K.-C., Cheng, W.-W., Ma, V. W.S., Yip, C., Lim, C. K.P., Ngan, R. K.C., Au, J. S.K., Chan, A., Lim, W. W.L., and Queen Elizabeth Hospital/Hong Kong Government,
(2005). Protein Chip Array Profiling Analysis in Patients with Severe Acute Respiratory Syndrome Identified Serum Amyloid A Protein as a Biomarker Potentially Useful in Monitoring the Extent of Pneumonia. Clin. Chem.
51: 47-55
[Abstract][Full Text]
Hass, M., Golnitz, U., Muller, S., Becker-Ziaja, B., Gunther, S.
(2004). Replicon System for Lassa Virus. J. Virol.
78: 13793-13803
[Abstract][Full Text]
Pannetier, D., Faure, C., Georges-Courbot, M.-C., Deubel, V., Baize, S.
(2004). Human Macrophages, but Not Dendritic Cells, Are Activated and Produce Alpha/Beta Interferons in Response to Mopeia Virus Infection. J. Virol.
78: 10516-10524
[Abstract][Full Text]
SBRANA, E., XIAO, S.-Y., GUZMAN, H., YE, M., TRAVASSOS DA ROSA, A. P. A., TESH, R. B.
(2004). EFFICACY OF POST-EXPOSURE TREATMENT OF YELLOW FEVER WITH RIBAVIRIN IN A HAMSTER MODEL OF THE DISEASE. Am J Trop Med Hyg
71: 306-312
[Abstract][Full Text]
Asper, M., Sternsdorf, T., Hass, M., Drosten, C., Rhode, A., Schmitz, H., Gunther, S.
(2004). Inhibition of Different Lassa Virus Strains by Alpha and Gamma Interferons and Comparison with a Less Pathogenic Arenavirus. J. Virol.
78: 3162-3169
[Abstract][Full Text]
Cheng, W. T. F., Li, C. K., Leung, T. F., Li, A. M.-c., Hon, K. L. E., Ng, P. C., Fok, T. F.
(2004). Ribavirin for Sars in Children. CLIN PEDIATR
43: 193-196
Richmond, J K., Baglole, D. J
(2003). Lassa fever: epidemiology, clinical features, and social consequences. BMJ
327: 1271-1275
[Full Text]
ATHAR, M. N., BAQAI, H. Z., AHMAD, M., KHALID, M. A., BASHIR, N., AHMAD, A. M., BALOUCH, A. H., BASHIR, K.
(2003). SHORT REPORT: CRIMEAN-CONGO HEMORRHAGIC FEVER OUTBREAK IN RAWALPINDI, PAKISTAN, FEBRUARY 2002. Am J Trop Med Hyg
69: 284-287
[Abstract][Full Text]
Wong, R. S M, Wu, A., To, K F, Lee, N., Lam, C. W K, Wong, C K, Chan, P. K S, Ng, M. H L, Yu, L M, Hui, D. S, Tam, J. S, Cheng, G., Sung, J. J Y
(2003). Haematological manifestations in patients with severe acute respiratory syndrome: retrospective analysis. BMJ
326: 1358-1362
[Abstract][Full Text]
Lukashevich, I. S., Tikhonov, I., Rodas, J. D., Zapata, J. C., Yang, Y., Djavani, M., Salvato, M. S.
(2003). Arenavirus-Mediated Liver Pathology: Acute Lymphocytic Choriomeningitis Virus Infection of Rhesus Macaques Is Characterized by High-Level Interleukin-6 Expression and Hepatocyte Proliferation. J. Virol.
77: 1727-1737
[Abstract][Full Text]
Lanford, R. E., Guerra, B., Lee, H., Averett, D. R., Pfeiffer, B., Chavez, D., Notvall, L., Bigger, C.
(2002). Antiviral Effect and Virus-Host Interactions in Response to Alpha Interferon, Gamma Interferon, Poly(I)-Poly(C), Tumor Necrosis Factor Alpha, and Ribavirin in Hepatitis C Virus Subgenomic Replicons. J. Virol.
77: 1092-1104
[Abstract][Full Text]
Marik, P. E., Bowles, S.
(2002). Analytic Reviews: Management of Patients Exposed to Biological and Chemical Warfare Agents. J Intensive Care Med
17: 147-161
[Abstract]
Gavin, P. J., Katz, B. Z.
(2002). Intravenous Ribavirin Treatment for Severe Adenovirus Disease in Immunocompromised Children. Pediatrics
110: e9-9
[Abstract][Full Text]
Borio, L., Inglesby, T., Peters, C. J., Schmaljohn, A. L., Hughes, J. M., Jahrling, P. B., Ksiazek, T., Johnson, K. M., Meyerhoff, A., O'Toole, T., Ascher, M. S., Bartlett, J., Breman, J. G., Eitzen, E. M. Jr, Hamburg, M., Hauer, J., Henderson, D. A., Johnson, R. T., Kwik, G., Layton, M., Lillibridge, S., Nabel, G. J., Osterholm, M. T., Perl, T. M., Russell, P., Tonat, K., for the Working Group on Civilian Biodefense,
(2002). Hemorrhagic Fever Viruses as Biological Weapons: Medical and Public Health Management. JAMA
287: 2391-2405
[Abstract][Full Text]
Lenz, O., ter Meulen, J., Klenk, H.-D., Seidah, N. G., Garten, W.
(2001). The Lassa virus glycoprotein precursor GP-C is proteolytically processed by subtilase SKI-1/S1P. Proc. Natl. Acad. Sci. USA
10.1073/pnas.221447598v1
[Abstract][Full Text]
Gupta, M., Mahanty, S., Bray, M., Ahmed, R., Rollin, P. E.
(2001). Passive Transfer of Antibodies Protects Immunocompetent and Immunodeficient Mice against Lethal Ebola Virus Infection without Complete Inhibition of Viral Replication. J. Virol.
75: 4649-4654
[Abstract][Full Text]
Fisher-Hoch, S. P., Hutwagner, L., Brown, B., McCormick, J. B.
(2000). Effective Vaccine for Lassa Fever. J. Virol.
74: 6777-6783
[Abstract][Full Text]
Bausch, D. G., Rollin, P. E., Demby, A. H., Coulibaly, M., Kanu, J., Conteh, A. S., Wagoner, K. D., McMullan, L. K., Bowen, M. D., Peters, C. J., Ksiazek, T. G.
(2000). Diagnosis and Clinical Virology of Lassa Fever as Evaluated by Enzyme-Linked Immunosorbent Assay, Indirect Fluorescent-Antibody Test, and Virus Isolation. J. Clin. Microbiol.
38: 2670-2677
[Abstract][Full Text]
Seiler, P., Senn, B. M., Klenerman, P., Kalinke, U., Hengartner, H., Zinkernagel, R. M.
(2000). Additive Effect of Neutralizing Antibody and Antiviral Drug Treatment in Preventing Virus Escape and Persistence. J. Virol.
74: 5896-5901
[Abstract][Full Text]
Leyssen, P., De Clercq, E., Neyts, J.
(2000). Perspectives for the Treatment of Infections with Flaviviridae. Clin. Microbiol. Rev.
13: 67-82
[Abstract][Full Text]
Franchini, G., Ambinder, R. F., Barry, M.
(2000). Viral Disease in Hematology. ASH Education Book
2000: 409-423
[Abstract][Full Text]
Balfour, H. H.
(1999). Antiviral Drugs. NEJM
340: 1255-1268
[Full Text]
Franz, D. R., Jahrling, P. B., Friedlander, A. M., McClain, D. J., Hoover, D. L., Bryne, W. R., Pavlin, J. A., Christopher, G. W., Eitzen, E. M. Jr
(1997). Clinical Recognition and Management of Patients Exposed to Biological Warfare Agents. JAMA
278: 399-411
[Abstract]
McJunkin, J. E., Khan, R., de los Reyes, E. C., Parsons, D. L., Minnich, L. L., Ashley, R. G., Tsai, T. F.
(1997). Treatment of Severe La Crosse Encephalitis With Intravenous Ribavirin Following Diagnosis by Brain Biopsy. Pediatrics
99: 261-261
[Full Text]
Barry, M., Russi, M., Armstrong, L., Geller, D., Tesh, R., Dembry, L., Gonzalez, J. P., Khan, A. S., Peters, C. J.
(1995). Treatment of a Laboratory-Acquired Sabia Virus Infection. NEJM
333: 294-296
[Full Text]
Balfour, H. H. Jr, Englund, J. A.
(1989). Antiviral Drugs in Pediatrics. Arch Pediatr Adolesc Med
143: 1307-1316
[Abstract]
CRUMPACKER, C., HEAGY, W., BUBLEY, G., MONROE, J. E., FINBERG, R., HUSSEY, S., SCHNIPPER, L., LUCEY, D., LEE, T. H., MCLANE, M. F., ESSEX, M., MULDER, C.
(1987). Ribavirin Treatment of the Acquired Immunodeficiency Syndrome (AIDS) and the Acquired-Immunodeficiency-Syndrome-Related Complex (ARC) A Phase 1 Study Shows Transient Clinical Improvement Associated with Suppression of the Human Immunodeficiency Virus and Enhanced Lymphocyte Proliferation. ANN INTERN MED
107: 664-674
[Abstract]
Crotty, S., Cameron, C. E., Andino, R.
(2001). RNA virus error catastrophe: Direct molecular test by using ribavirin. Proc. Natl. Acad. Sci. USA
98: 6895-6900
[Abstract][Full Text]
Lenz, O., ter Meulen, J., Klenk, H.-D., Seidah, N. G., Garten, W.
(2001). The Lassa virus glycoprotein precursor GP-C is proteolytically processed by subtilase SKI-1/S1P. Proc. Natl. Acad. Sci. USA
98: 12701-12705
[Abstract][Full Text]