Biomedical subjects
D A Enria
Publications and source records attributed to D A Enria.
Clinical manifestations of New World hantaviruses.
Explore the source record for details and available documents.
Rodent-borne emerging viral zoonosis. Hemorrhagic fevers and hantavirus infections in South America.
Hantaviruses and arenaviruses are naturally occurring viruses of rodents. Four South American hemorrhagic fevers caused by arenaviruses have emerged in the last 5 decades. All have similar clinical manifestations, with a case-fatality rate as high as 15% to 30%. Hantavirus infections have been increasingly recognized in South America since the description in 1993 of Hantavirus pulmonary syndrome. Given the diversity of rodent species in the region, it can be foreseen that many other viruses will be discovered, and some of them will be causing human illnesses of high public health impact.
[Hantavirus pulmonary syndrome in southern Argentina].
Andes virus was identified in 1995 as the etiologic agent of Hantavirus Pulmonary Syndrome (HPS) in Southern Argentina. We describe herein the main clinical characteristics of 25 HPS confirmed cases acquired in this area between 1993 and September 1999. The mean age was 34 years (range 11-70), with 72% males. Clinical characteristics were similar to those previously reported for Sin Nombre virus (SNV) cases. However, in this group of patients we also observed conjuntival injection in 10/25 (42%), facial flushing in 8/25 (33%), pharyngeal congestion in 7/25 (29%) and petechiae in 3/25 (12%). On the other hand, BUN was increased in 83% of cases (mean 0.77 g/l range 0.31-2.01). Mean serum creatinine concentration was 26.8 mg/l (range: 8.1-110 mg/l) with serum creatinine being higher than 20 mg/l in 8/15 patients (53%). Urinalysis was abnormal in 12/12 cases and was characterized by presence of proteins, red blood cells and granular casts. Aminotransferases were increased in 90% of cases with levels 5-10 times over normal values in 50% of cases. Serum creatine kinase concentration was elevated in 11/14 cases. Two patients required hemodialysis. Case fatality rate was 44% (11/25) and 10 of these cases died among the first 10 days of illness. Mononuclear myocarditis was observed in two cases, a finding that has not been reported for SNV cases. During the 1996 HPS outbreak in Southern Argentina due to Andes virus, there were epidemiological and molecular evidences of person-to-person transmission, a feature not previously shown for other members of the hantavirus genus. These data would also be indicative of some distinctive clinical characteristics of HPS caused by Andes virus, with more frequent renal involvement than in SNV cases.
Protective efficacy of a live attenuated vaccine against Argentine hemorrhagic fever. AHF Study Group.
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.
New World hantaviruses.
Since the initial description in 1993 of hantavirus pulmonary syndrome and its novel aetiological agent, Sin Nombre virus, our knowledge of the epidemiology of New World hantaviruses has continued to evolve. After the identifying outbreak in the southwestern US, four hantaviruses have been identified in North America with specific rodent hosts and associated with a number of sporadic cases. This stability of case recognition in North America is in contrast to the multiple outbreaks and endemic cases in South America. Despite a plethora of New World hantaviruses and new evidence of person-to-person transmission, the ecological and personal determinants of this human infection remain a mystery.
[Hantavirus emergence in the Americas and in Argentina].
Explore the source record for details and available documents.
New hantaviruses causing hantavirus pulmonary syndrome in central Argentina.
Explore the source record for details and available documents.
Characterization of Oliveros virus, a new member of the Tacaribe complex (Arenaviridae: Arenavirus).
Oliveros virus is an agent isolated in cell culture from Bolomys obscurus (Rodentia, Muridae, Sigmodontinae) captured on the central Argentine pampa. Oliveros virus was shown to be related to members of the Tacaribe complex of the family Arenaviridae by immunofluorescent antibody (IFA) tests, electrophoretic pattern of viral proteins, and morphology as observed by electron microscopy. It was distinct from 12 other arenaviruses by a combination of plaque-reduction neutralization tests, comparison of endpoint titers among cross-IFA tests, and comparison of viral RNA sequence data. This agent is the third new arenavirus from South America described within the last three years.
[Retrospective detection of hantavirus clinical infections in Argentina].
Hantavirus activity in rodents and human beings in Argentina has been known since the 1980's. In this study, we retrospectively investigated hantavirus infections among Argentine Hemorrhagic Fever (AHF) cases notified between 1987 and 1994, without virological confirmation. IgG and IgM antibodies to hantavirus were tested by ELISA. Among 1028 patients included in the study, we found 13 recent infections (1.26%) and 13 remote infections (1.26%). IgG antibodies determined in 745 healthy persons living in the same localities of recent infection cases, gave only one positive result (0.13%). Nine of the 13 recent infections had the clinical presentation of Hemorrhagic Fever with Renal Syndrome (HFRS) while the other four were in the form of Hantavirus Pulmonary Syndrome (HPS). We performed a clinical and epidemiological comparison between the nine patients with FHSR and two paired control groups: one with confirmed AHF and the other with Febrile Syndrome of Undetermined Etiology (FSUE), which were negative for hantavirus, Junin and LCM. There were no differences between clinical signs or symptoms. Nevertheless, normal or high leucocyte counts, with thrombocytopenia, hemoconcentration, high creatinine levels and proteinuria in HFRS cases resulted useful for differential diagnosis. These results showed the coexistence of Junin virus and hantaviruses in the endemic area of AHF, and indicate the importance of including the infection with these viruses in the differential diagnosis of hemorrhagic fevers and respiratory distress syndromes of unknown etiology. The clinical variability found could be related to the presence of more than one hantavirus serotype in our country.
Antiviral treatment of Argentine hemorrhagic fever.
Argentine hemorrhagic fever is a systemic viral disease caused by Junin virus, with a mortality of 15-30% in untreated individuals. Current specific therapy is highly effective in reducing mortality, and consists of the early administration of immune plasma in defined doses of specific neutralizing antibodies per kg of body weight. However, several reasons suggest the need to investigate alternative therapies. Ribavirin, a broad spectrum antiviral agent, is effective in the treatment of other viral hemorrhagic fevers, and the studies done with Junin virus infections to date indicate that this drug may also have a beneficial effect in Argentine hemorrhagic fever.
Tolerance and antiviral effect of ribavirin in patients with Argentine hemorrhagic fever.
Tolerance and antiviral effect of ribavirin was studied in 6 patients with Argentine hemorrhagic fever (AHF) of more than 8 days of evolution. Administration of ribavirin resulted in a neutralization of viremia and a drop of endogenous interferon titers. The average time of death was delayed. A reversible anemia was the only adverse effect observed. From these results, we conclude that ribavirin has an antiviral effect in advanced cases of AHF, and that anemia, the only secondary reaction observed, can be easily managed. The possible beneficial effect of ribavirin during the initial days of AHF is discussed.
Junin virus isolation from lympho-mononuclear cells of patients with Argentine hemorrhagic fever.
Detection of viremia was attempted by three different methods in 30 cases of Argentine hemorrhagic fever (AHF). Cocultivation of peripheral blood mononuclear cells (PBMC) with Vero cell monolayers was the most sensitive, detecting Junin virus (JV) in 96% of the cases. Inoculation of whole blood into suckling mice and on Vero cells rendered 53 and 46% of positive isolations, respectively. The results presented suggest that PBMC are infected with JV during the acute period of AHF. JV was isolated with decreasing frequency up to 3 days after treatment with immune plasma, but no virus was recovered from PBMC during early convalescence.
Correlation between endogenous interferon and the clinical evolution of patients with Argentine hemorrhagic fever.
To explore the endogenous interferon levels in patients of Argentine hemorrhagic fever (AHF) with different clinical evolution of the disease, 29 fatal and 33 surviving cases of AHF were analyzed. As previously reported, the titers of endogenous alpha-IFN in patients with AHF are very high, generally between 2,000 and 64,000 IU/ml. Thus far, these are the highest levels of circulating interferon detected in any human viral disease. In this study it was found that during the second week of evolution the titers of interferon were significantly higher in fatal cases than in survivors. Therefore, very high levels of interferon have a prognostic value in AHF.
[Late neurologic syndrome in patients with Argentinian hemorrhagic fever treated with immune plasma].
Explore the source record for details and available documents.
Importance of dose of neutralising antibodies in treatment of Argentine haemorrhagic fever with immune plasma.
P6 a retrospective study outcome in patients with Argentine haemorrhagic fever was associated with the amount of neutralising antibodies against Junin virus present in the transfused units of immune plasma. Low doses of neutralising antibodies were associated with higher mortality. A prospective study gave comparable results. A dose of no less than 3000 therapeutic units of neutralising antibodies per kg body weight is recommended. It is also suggested that the lack of effectiveness of immune plasma in the treatment of other viral haemorrhagic fevers, such as Lassa fever and Crimean-Congo haemorrhagic fever, may be due to a low dose of the specific neutralising antibodies.
Endogenous interferon in Argentine hemorrhagic fever.
The induction of endogenous interferon (IFN) was studied in 28 cases of Argentine hemorrhagic fever (AHF), a severe systemic disease caused by Junin virus. Serum samples were taken daily during the acute period, both before and after administration of immune plasma. This form of treatment has been found to reduce mortality when given early in the course of AHF. High titers of circulating IFN were present in the serum samples taken before treatment. IFN titers drastically dropped after transfusion of immune plasma. The antiviral activity was stable at pH 2 and was completely neutralized only by antibodies against IFN-alpha. Thus, we concluded that circulating endogenous IFN in patients with AHF can be considered as typical IFN-alpha. Fever, chills, and backache were associated with the higher levels of IFN. An inverse correlation between days of evolution of the disease and IFN activity was also observed.
Hantavirus infection in children in Argentina.
Clinical hantavirus infection was diagnosed in five Argentine children ages 5 to 11 years by immunoglobulin M (IgM)- capture enzyme-linked immunosorbent assay using Sin Nombre virus (SNV) antigens. Death in three of the children was associated with absence of detectable IgG to SNV antigens. An additional two cases in healthy children were studied: one, a breast-fed 15-month-old whose mother died of suspected hantavirus pulmonary syndrome (HPS) 8 months previously, had hantavirus IgG (> 1:6400); a second, whose mother survived HPS during month three of pregnancy, apparently had maternal antibodies no longer detectable 1 year after birth.