Protective efficacy of a live attenuated vaccine against Argentine hemorrhagic fever. AHF Study Group

Fil: Maiztegui, Julio I. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas; Argentina.Fil: McKee Jr, K. T. Womack Army Medical Center, Fort Bragg, North Carolina; Estados Unidos.Fil: Barrera Oro, J G. ANLIS Dr.C.G.Malbrán; Argentina.Fil: Harrison, L H. University of Pittsburgh Graduate School of Public Health,Pittsburgh, Pennsylvania; Estados Unidos.Fil: Gibbs, P H. Division of Disease Assessment, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland 21701; Estados Unidos.Fil: Feuillade, María Rosa. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas; Argentina.Fil: Enria, Delia. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas; Argentina.Fil: Briggiler, Ana M. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas; Argentina.Fil: Levis, Silvana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas; Argentina.Fil: Ambrosio, Ana María. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas; Argentina.Fil: Halsey, N A. Department of International Health, Johns Hopkins Medical Institutions, Baltimore, Maryland; Estados Unidos.Fil: Peters, C J. Special Pathogens Branch, Centers for Disease Control, Atlanta, Georgia; Estados Unidos.Argentine hemorrhagic fever (AHF), caused by the arenavirus Junin, is a major public health problem among agricultural workers in Argentina. A prospective, randomized, double-blind, placebo-controlled, efficacy trial of Candid 1, a live attenuated Junin virus vaccine, was conducted over two consecutive epidemic seasons among 6500 male agricultural workers in the AHF-endemic region. Twenty-three men developed laboratory-confirmed AHF during the study; 22 received placebo and 1 received vaccine (vaccine efficacy 95%; 95% confidence interval [CI], 82%-99%). Three additional subjects in each group developed laboratory-confirmed Junin virus infection associated with mild illnesses that did not fulfill the clinical case definition for AHF, yielding a protective efficacy for prevention of any illness associated with Junin virus infection of 84% (95% CI, 60%-94%). No serious adverse events were attributed to vaccination. Candid 1, the first vaccine for the prevention of illness caused by an arenavirus, is safe and highly efficacious

Junin virus vaccines

Fil: Enria, Delia A. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas; Argentina.Fil: Barrera Oro, J. G. ANLIS Dr.C.G.Malbrán. CONICET; Argentina.Argentine hemorrhagic fever (AHF) was recognized as a new clinical entity from the richest farming region of Argentina in the 1950s (Arribalzaga 1955). The etiologic agent of this disease, Junin virus (JUN), was isolated in 1958 (Parodi et al. 1958; Piroski et al. 1959). JUN belongs to the Arenaviridae family, which includes other rodent-borne pathogens which are important causes of hemorrhagic fever in Africa, (Lassa) and South America (Machupo, Guanarito, and Sabia viruses). The Arenaviridae comprises at least 20 recognized members. Arenaviruses are enveloped RNA viruses, and are divided into two groups, with low level antigenic relatedness: the Old World group, and New World group or Tacaribe complex. Two antigenic subgroups were defined within the New World arenaviruses. JUN is contained into the first group, together with Amapari, Latino, Machupo and Tacaribe viruses. Phylogenetic analysis have shown that Old World and New World arenaviruses occupied two distinct clades, and that New World arenaviruses comprise three evolutionary lineages, named A, B, and C. JUN is contained in lineage B, together with the other three agents causing South American hemorrhagic fevers (Enria et al. 1999a)

Clinical case definitions for Argentine hemorrhagic fever

Fil: Harrison, Lee H. University of Pittsburgh Graduate School of Public Health,Pittsburgh, Pennsylvania; Estados Unidos.Fil: Halsey, Neal A. Department of International Health, Johns Hopkins Medical Institutions, Baltimore, Maryland; Estados Unidos.Fil: McKee, Kelly T. Womack Army Medical Center, Fort Bragg, North Carolina; Estados Unidos.Fil: Peters, Clarence J. Special Pathogens Branch, Centers for Disease Control, Atlanta, Georgia; Estados UnidosFil: Barrera Oro, Julio G. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas; Argentina.Fil: Briggiler, Ana M. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas; Argentina.Fil: Feuillade, Maria Rosa. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas; Argentina.Fil: Maiztegui, Julio I. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas; Argentina.Argentine hemorrhagic fever (AHF) is a potentially lethal infection in Argentina. The case-fatality ratio is >15%, but treatment reduces the mortality rate to <1%. Diagnosis is based on clinical and laboratory criteria, but no case definition has been validated. A chart review was conducted for patients hospitalized with suspected AHF. Individuals with a fourfold rise in antibody titer were classified as cases. The combination of a platelet count of <100,000/mm3 and a white blood cell (WBC) count of <2,500/mm3 had a sensitivity and specificity of 87% and 88%, respectively, thus suggesting that the use of these criteria in a case definition would be helpful for epidemiological studies of AHF. The combination of a platelet count of <100,000/mm3 and a WBC count of <4,000/mm3 had a sensitivity of 100% and a specificity of 71%; the use of these criteria in a case definition should be helpful for screening patients for therapy with immune plasma in the region where AHF is endemic