West Nile Virus in the New World: trends in the spread and proliferation of West Nile Virus in the Western Hemisphere.

The observed patterns and variations in the ecology, epidemiology, distribution and prevalence of the West Nile Virus (WNV) in different areas of the Western Hemisphere make this pathogen of particular importance as a model for understanding the potential risk factors associated with emerging pathogens worldwide, particularly those involving zoonotic pathogens whose epidemiology involves the potential for vertical transmission in arthropod vector species, and horizontal and vertical transmission within and among vertebrate host species. Record numbers of human WNV cases were recorded in Canada during 2007, with >50% more cases than documented in any previous year. Although overall numbers of human infections recorded in the United States were not exceptionally high during 2007 relative to epidemic levels reported in 2002 and 2003, the state of Oklahoma reported that the highest-ever number of human WNV cases and the numbers of human cases recorded in Canada were 50% higher than previous record levels recorded in 2003. The record and near-record numbers of human WNV infections recorded in several regions of North America during 2007 have important implications for the future management and surveillance of WNV vectors and reservoirs in North America. The spatiotemporal distribution of WNV infections in humans and animals recorded during 2007 in North America and South America have important implications for the surveillance and management of public health threats from WNV in the Western Hemisphere. Serological surveys conducted in areas of intense WNV transmission in the United States have reported low prevalence of antibodies to WNV in human s populations, indicating that additional epidemic outbreaks of human disease from WNV can be expected in the future.

[Emerging viral zoonoses: hantavirus infections]. / Zoonosis virales emergentes: las infecciones por hantavirus.

Hantaviruses are rodent-borne agents belonging to the Bunyaviridae family. These viruses, which are found throughout Europe, Asia and the Americas, are maintained by different species of rodents, in which they produce chronic, inapparent infections. Humans become infected through contact with urine, saliva or faeces from infected rodents, mainly via the aerosol route. In humans, clinical disease occurs in the form of two major syndromes: haemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary syndrome (HPS). Haemorrhagic fever with renal syndrome mainly occurs in Europe and Asia and HPS has only ever been reported in the Americas. Person-to-person transmission of hantaviruses, although uncommon, was described during an outbreak of HPS in southern Argentina. Most epidemics of HFRS and HPS occur in areas with large populations of rodents that have a relatively high prevalence of infection.

Phylogenetic relationships of dengue-1 viruses from Argentina and Paraguay.

We sequenced the Capsid-pre Membrane (C/prM) and the Envelope-Nonstructural protein 1 (E/NS1) regions of 24 recent isolates of dengue-1 (DEN-1) from South America. This included 12 Argentinean and 11 Paraguayan DEN-1 strains isolated in 2000 plus a Paraguayan strain isolated in 1988. These sequences were compared with published sequences of DEN-1 isolated worldwide to determine the origin of these isolates. Pairwise comparisons of strains from Paraguay and Argentina revealed a nucleotide divergence of 0-5% in the E/NS1 region and 0-3% in the C/prM region. Our results showed that these viruses belong to the same genotype, but can be separated into two clades. Interestingly, both clades circulated simultaneously in the same geographic area during the 2000 outbreaks. Amino acid differences were found between both clades in the C/prM region at position 100 (Lys vs. Arg) and in the E/NS1 region at positions 722 (Ala vs. Thr). Although the geographic movement of DEN-1 virus can not be unequivocally traced from the genetic relationship determined here, our results suggest that the recent epidemics in Argentina and Paraguay were due to the re-emergence of a previously circulating strain, or to the virus circulating unnoticed, rather than to the introduction of a new genotype.

[Secondary serologic responses to dengue epidemic in 1998 in Salta, Argentina, where other flavivirus co-circulate]. / Respuestas serológicas secundarias en la epidemia de dengue de 1998 en Salta, Argentina, donde co-circulan otros flavivirus.

In 1998, a dengue outbreak (serotype 2) occurred in Salta province in Northern Argentina, following the first detection of dengue in the same area in 1997. We classified the serologic response of cases from 1998 as primary or secondary, since the risk of severe disease is greater for secondary cases. We studied 154 cases by plaque reduction neutralization and hemagglutination inhibition tests. Thirty-eight cases (25%) were classified as primary serologic responses and 84 cases (54%) as secondary responses. Thirty-two cases (21%) with borderline IgG titers could not be classified. Previous exposure to potentially cross-reacting flaviviruses (Saint Louis Encephalitis [SLE] and Yellow Fever [YF] viruses) was analyzed, as a possible cause of the secondary response pattern. Our results indicated that among cases classified as dengue secondary response, 83% could be attributed to previous SLE or YF exposure or serologic cross-reactivity. Vaccination against YF virus was at most a minor contributor to the secondary response pattern. The finding of a positive YF serologic result among persons not vaccinated may indicate silent circulation of YF in a region that can support both urban and jungle cycles. Other cases showing dengue secondary responses remained unexplained, suggesting the unrecognized occurrence of a previous infection with other dengue serotypes or of flaviviruses other than SLE or YF.

Respuestas serológicas secundarias en la epidemia de dengue de 1998 en Salta, Argentina, donde co-circulan otros flavivirus. / [Secondary serologic responses to dengue epidemic in 1998 in Salta, Argentina, where other flavivirus co-circulate]

In 1998, a dengue outbreak (serotype 2) occurred in Salta province in Northern Argentina, following the first detection of dengue in the same area in 1997. We classified the serologic response of cases from 1998 as primary or secondary, since the risk of severe disease is greater for secondary cases. We studied 154 cases by plaque reduction neutralization and hemagglutination inhibition tests. Thirty-eight cases (25

) were classified as primary serologic responses and 84 cases (54

) as secondary responses. Thirty-two cases (21

) with borderline IgG titers could not be classified. Previous exposure to potentially cross-reacting flaviviruses (Saint Louis Encephalitis [SLE] and Yellow Fever [YF] viruses) was analyzed, as a possible cause of the secondary response pattern. Our results indicated that among cases classified as dengue secondary response, 83

could be attributed to previous SLE or YF exposure or serologic cross-reactivity. Vaccination against YF virus was at most a minor contributor to the secondary response pattern. The finding of a positive YF serologic result among persons not vaccinated may indicate silent circulation of YF in a region that can support both urban and jungle cycles. Other cases showing dengue secondary responses remained unexplained, suggesting the unrecognized occurrence of a previous infection with other dengue serotypes or of flaviviruses other than SLE or YF.

[Hantavirus pulmonary syndrome in southern Argentina]. / Síndrome pulmonar por Hantavirus en el sur andino argentino.

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.

Genetic diversity of the Junin virus in Argentina: geographic and temporal patterns.

RNA was purified from 39 strains of cell-cultured Junin virus (JUN) from central Argentina, which included both human- and rodent-derived isolates (a total of 26 and 13, respectively), as well as from 2 laboratory JUN strains, XJ Cl3 and XJ #44. JUN-specific primers were used to amplify a 511-nucleotide (nt) fragment of the nucleocapsid protein gene and a 495-nt fragment of the glycoprotein 1 (GP1) gene. Genetic diversity among JUN strains studied was up to 13% at the nt level and up to 9% at the amino acid (aa) level for the GP1 gene and up to 9% (nt) and 4% (aa) for the NP gene. Phylogenetic analyses of both genes revealed three distinct clades. The first clade was composed of the JUN strains from the center of the endemic area and included the majority of JUN strains analyzed in the current study. The second clade contained 4 JUN strains isolated between 1963 and 1971 from Cordoba Province, the western-most edge of the known endemic area. The third clade contained 4 JUN strains that originated from Calomys musculinus trapped in Zarate, the northeastern edge of the known endemic area. Certain JUN sequences, which were obtained from GenBank and identified as XJ, XJ #44, and Candid #1 strains, appeared to form a separate clade. Over 400 nt of the GP1 and GP2 genes were additionally sequenced for 7 JUN strains derived from patients with different clinical presentations and outcomes of Argentine hemorrhagic fever. Analysis of the corresponding aa sequences did not allow us to attribute any particular genetic marker to the changing severity or clinical form of the human disease.

Relationship between hematopoietic growth factors levels and hematological parameters in Argentine hemorrhagic fever.

Argentine hemorrhagic fever (AHF) is a viral disease caused by Junin virus and characterized by hematologic and neurological involvement. The main hematologic features are leukopenia, thrombocytopenia, and bone marrow hypoplasia. Hematopoietic growth factors serum levels were measured by ELISA technique in forty-eight patients with confirmed diagnosis of AHF. Patients were classified according to the clinical picture in 15 severe (SCF), 17 moderate (MoCF), and 16 mild (MiCF) cases. Erythropoietin levels were decreased in 28 of 45 patients and raised in 4 SCF patients. Twenty-four of 38 patients had high G-CSF levels at admittance in accordance with clinical picture severity, while IL-3, GM-CSF, and TGF-beta were normal in most cases. A direct correlation was found between G-CSF and TNF-alpha levels. Thrombopoietin levels were found to be raised in 19 of 21 patients. In conclusion, the low levels of Epo may contribute to the severe bone marrow erythroblastopenia described in AHF patients, while G-CSF seems to be a marker of illness severity.

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.

[Report on a leptospirosis outbreak in the city of Santa Fe, Argentina, March-April 1998]. / Descripción de un brote de leptospirosis en la ciudad de Santa Fe, Argentina, marzo-abril de 1998.

In March-April 1998 in a neighborhood in the city of Santa Fe, Argentina, there was an outbreak of an acute disease characterized by fever, headaches, and intense myalgias. This article presents the studies surrounding this outbreak and the attempts to identify the source and the mode of transmission. The epidemiological, serological, and clinical findings indicated that the causative agent was Leptospira interrogans. As a screening test, macroscopic agglutination with heat-resistant antigen was applied, followed by the ELISA test, and, as a confirmatory test, microscopic agglutination for 10 serotypes of L. interrogans. The study covered 32 persons, 8 dogs, and 8 water samples. Among the 32 persons, 12 cases were confirmed, 2 were suspicious, and 18 were negative. Six dogs were found to be infected, and motile spirochetes were found in the water samples. The human sera reacted with the ballum, canicola, icterohaemorrhagiae, and pyrogenes serotypes; the canine sera reacted with the ballum, canicola, and pomona serotypes. The coagglutination found in all the confirmed cases indicates that they were acute cases of leptospirosis, but it was impossible to identify the causal serotype. Except for the index case, the disease was not recognized clinically. Several facts suggest that the outbreak was caused by rain that had flooded the study area. The results of this study emphasize the need for active surveillance of leptospirosis when there are floods and other natural disasters.

[Outbreak of Dengue-2 virus in Salta, Argentina, 1988]. / Epidemia por virus dengue-2 en Salta, Argentina, 1998.

Dengue (DEN) reemergence was first detected in Salta, Argentina, in 1997. It was confirmed by serology and PCR that DEN-2 virus was responsible for sporadic cases and indigenous transmission. A laboratory-based surveillance system allowed the detection of an outbreak in Salta several months later. In total, 378 DEN cases were laboratory diagnosed out of 646 (58%) studied. The cases were distributed in 10 localities of the province between January 3rd and May 31st, 1998. One DEN-2 viral isolation and 4 PCR products were obtained from patients coming from Orán and Embarcación localities. Male and female cases occurred at a similar rate (1:1), with adult cases (82.5%) nearly five times greater than for children under 15 years-old (17.5%). Clinically, all cases corresponded to classic DEN. This is the first time that a DEN outbreak has been laboratory-diagnosed in Argentina and also the first time that DEN virus has been isolated in this country.

Síndrome pulmonar por Hantavirus en el sur andino argentino. / [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.

Epidemia por virus dengue-2 en Salta, Argentina, 1998. / [Outbreak of Dengue-2 virus in Salta, Argentina, 1988]

Dengue (DEN) reemergence was first detected in Salta, Argentina, in 1997. It was confirmed by serology and PCR that DEN-2 virus was responsible for sporadic cases and indigenous transmission. A laboratory-based surveillance system allowed the detection of an outbreak in Salta several months later. In total, 378 DEN cases were laboratory diagnosed out of 646 (58

) studied. The cases were distributed in 10 localities of the province between January 3rd and May 31st, 1998. One DEN-2 viral isolation and 4 PCR products were obtained from patients coming from Orán and Embarcación localities. Male and female cases occurred at a similar rate (1:1), with adult cases (82.5

) nearly five times greater than for children under 15 years-old (17.5

). Clinically, all cases corresponded to classic DEN. This is the first time that a DEN outbreak has been laboratory-diagnosed in Argentina and also the first time that DEN virus has been isolated in this country.

Hantavirus reservoir hosts associated with peridomestic habitats in Argentina.

Five species of sigmodontine rodents have been identified in Argentina as the putative reservoirs of six circulating hantavirus genotypes. Two species of Oligoryzomys are associated with the genotypes causing hantavirus pulmonary syndrome, Oligoryzomys flavescens for Lechiguanas and O. longicaudatus for Andes and Oran genotypes. Reports of human cases of hantavirus pulmonary syndrome prompted rodent trapping (2,299 rodents of 32 species during 27,780 trap nights) at potential exposure sites in three disease-endemic areas. Antibody reactive to Sin Nombre virus was found in six species, including the known hantavirus reservoir species. Risk for peridomestic exposure to host species that carry recognized human pathogens was high in all three major disease-endemic areas.

Dengue reemergence in Argentina.

Aedes aegypti, eradicated from Argentina in 1963, has now reinfested the country as far south as Buenos Aires. In 1997, four persons with travel histories to Brazil, Ecuador, or Venezuela had confirmed dengue, and surveillance for indigenous transmission allowed the detection of 19 dengue cases in Salta Province. These cases of dengue are the first in Argentina since 1916 and represent a new southern extension of dengue virus.

An outbreak of hantavirus pulmonary syndrome, Chile, 1997.

An outbreak of 25 cases of Andes virus-associated hantavirus pulmonary syndrome (HPS) was recognized in southern Chile from July 1997 through January 1998. In addition to the HPS patients, three persons with mild hantaviral disease and one person with asymptomatic acute infection were identified. Epidemiologic studies suggested person-to-person transmission in two of three family clusters. Ecologic studies showed very high densities of several species of sigmodontine rodents in the area.