Serum levels of interleukin-6 are linked to the severity of the disease caused by Andes Virus.

Andes virus (ANDV) is the etiological agent of hantavirus cardiopulmonary syndrome in Chile. In this study, we evaluated the profile of the pro-inflammatory cytokines IL-1ß, IL-12p70, IL-21, TNF-α, IFN-γ, IL-10 and IL-6 in serum samples of ANDV-infected patients at the time of hospitalization. The mean levels of circulating cytokines were determined by a Bead-Based Multiplex assay coupled with Luminex detection technology, in order to compare 43 serum samples of healthy controls and 43 samples of ANDV-infected patients that had been categorized according to the severity of disease. When compared to the controls, no significant differences in IL-1ß concentration were observed in ANDV-infected patients (p = 0.9672), whereas levels of IL-12p70 and IL-21 were significantly lower in infected cases (p = <0.0001). Significantly elevated levels of TNF-α, IFN-γ, IL-10, and IL-6 were detected in ANDV-infected individuals (p = <0.0001, 0.0036, <0.0001, <0.0001, respectively). Notably, IL-6 levels were significantly higher (40-fold) in the 22 patients with severe symptoms compared to the 21 individuals with mild symptoms (p = <0.0001). Using multivariate regression models, we show that IL-6 levels has a crude OR of 14.4 (CI: 3.3-63.1). In conclusion, the serum level of IL-6 is a significant predictor of the severity of the clinical outcome of ANDV-induced disease.

Association of Single-Nucleotide Polymorphisms in IL28B, but Not TNF-α, With Severity of Disease Caused by Andes Virus.

BACKGROUND: Andes virus (ANDV) is the sole etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in Chile, with a fatality rate of about 35%. Individual host factors affecting ANDV infection outcome are poorly understood. In this case-control genetic association analysis, we explored the link between single-nucleotide polymorphisms (SNPs) rs12979860, rs8099917 and rs1800629 and the clinical outcome of ANDV-induced disease. The SNPs rs12979860 and rs8099917 are known to play a role in the differential expression of the interleukin 28B gene (IL28B), whereas SNP rs1800629 is implicated in the expression of tumor necrosis factor α gene (TNF-α). METHODS: A total of 238 samples from confirmed ANDV-infected patients collected between 2006 and 2014, and categorized according to the severity of the disease, were genotyped for SNPs rs12979860, rs8099917, and rs1800629. RESULTS: Analysis of IL28B SNPs rs12979860 and rs8099917 revealed a link between homozygosity of the minor alleles (TT and GG, respectively), displaying a mild disease progression, whereas heterozygosity or homozygosity for the major alleles (CT/CC and TG/TT, respectively) in both IL28B SNPs is associated with severe disease. No association with the clinical outcome of HCPS was observed for TNF-α SNP rs1800629 (TNF -308G>A). CONCLUSIONS: The IL28B SNPs rs12979860 and rs8099917, but not TNF-α SNP rs1800629, are associated with the clinical outcome of ANDV-induced disease, suggesting a possible link between IL28B expression and ANDV pathogenesis.

Certificación de la eliminación de sarampión, rubéola y SRC en Chile / Certification of elimination of measles, rubella and CRS in Chile

Debido al éxito en la eliminación del sarampión, rubéola y Síndrome Rubéola Congénito alcanzado en América, la Organización Panamericana de la Salud solicitó verificar la eliminación de estas enfermedades en los países de la región. Chile ratificó mediante Resolución a un comité nacional de expertos que revisó la información entregada por los equipos técnicos, en los siguientes componentes: epidemiología del sarampión, rubéola y SRC; calidad de la vigilancia; epidemiología molecular; sostenibilidad del programa de inmunizaciones y cohortes de población vacunada. La información obtenida de diversas fuentes permitió integrar la evidencia y determinar si los datos eran válidos, completos, representativos y consistentes. Esta publicación describe las etapas de la certificación y la información evaluada por el comité nacional ad hoc. Sus conclusiones serán ratificadas por el comité internacional, el que certificará si Chile cumple con los criterios para la eliminación, proceso que se espera culmine en diciembre 2011. Debido al constante riesgo de importación de estos virus desde otras partes del mundo, persisten muchos retos para mantener la eliminación en el tiempo.

Due to the success in the elimination of measles, rubella and CRS reached in the Americas, PAHO requested the verification of the elimination of these diseases in the countries of the region. Chile ratified by means of a resolution a National Committee of Experts, which revised the information provided by the technical teams in the following components: Epidemiology of measles, rubella and CRS; quality of the surveillance; molecular epidemiology; sustainability of the Immunization Program and cohorts of vaccinated population. The information gathered from different sources allowed to integrate the evidence provided and to determine if the data were valid, complete, representatives and consistent. In this paper we describe thecertification steps and the information evaluated by the ad-hoc national committee. Their conclusions will be ratified by the International Committee, which will certify if Chile fulfills the criteria for elimination, a process that is expected to end during December 2011.

Enhanced surveillance for congenital rubella syndrome following mass rubella vaccination of girls and reproductive-aged women.

Chile was the first country in the Americas to conduct surveillance for congenital rubella syndrome (CRS) as part of screening for common causes of congenital birth defects (referred to as TORCH pathogens). The surveillance system identified 15 CRS cases in 1999 and 2 cases in 2000, and it has identified no CRS cases since 2000. CRS surveillance in Chile meets recommended surveillance standards and may serve as a model for CRS surveillance in other countries.

Adenovirus and respiratory syncytial virus-adenovirus mixed acute lower respiratory infections in Chilean infants.

BACKGROUND: In Chile respiratory syncytial virus (RSV) and adenovirus (AD) are the principal viruses detected in acute lower respiratory infections (ALRI) in infants. An overview of AD pneumonia in Chile to detect annual trends and to compare the severity of single AD or mixed RSV-AD infections is presented. METHODS: Surveillance in 4927 infants hospitalized for ALRI has been performed from 1989 to 2001 using immunofluorescence assay (IFA) and viral isolation. Clinical features in 117 infants with single genotyped AD and 81 infants with mixed RSV-AD infections were analyzed. RESULTS: Adenovirus cases declined from 20% annually in the early 1990s to approximately 5% in the 2000 decade. Genotype 7h showed increasing prevalence in hospitalized cases. The mean annual burden of hospitalizations caused by AD in Santiago was estimated to be 0.6%. No difference was observed in duration of fever, oxygen requirement and hospital stay between groups. Lung consolidation was more frequent in AD cases than mixed cases (P < 0.01); interstitial pattern and hyperinflation prevailed in the mixed cases (P < 0.01). No child died. AD diagnosis was confirmed on admission by IFA in 17% of cases of RSV-AD and in 43% of cases of single AD ALRI. AD cases diagnosed early by IFA had worse clinical outcome than those diagnosed later by virus isolation (P < 0.05). CONCLUSIONS: AD cases declined since 1989. Mixed RSV-AD infections were not more severe than single AD etiology. AD cases admitted with positive IFA had worse prognoses than AD infections diagnosed later by virus isolation.

Prevalence of antibodies to hantavirus among family and health care worker contacts of persons with hantavirus cardiopulmonary syndrome: lack of evidence for nosocomial transmission of Andes virus to health care workers in Chile.

Nosocomial transmission of Andes virus has been documented in Argentina, but has not yet been proven in Chile. We studied 215 contacts (106 family member contacts and 109 health care worker contacts) of 20 index cases of hantavirus cardiopulmonary syndrome (HCPS) in Chile. The seroprevalence of IgG antibodies against Andes virus was 1.9% (95% confidence interval [CI] = 0.34-6.3%) among the family members and 0.0% (95% CI = 0-3.2%) among the health care workers. Our data suggest that there is no evidence for nosocomial transmission of Andes virus in region IX of Chile.

Complete sequence of the genome of the human isolate of Andes virus CHI-7913: comparative sequence and protein structure analysis.

We report here the complete genomic sequence of the Chilean human isolate of Andes virus CHI-7913. The S, M, and L genome segment sequences of this isolate are 1,802, 3,641 and 6,466 bases in length, with an overall GC content of 38.7%. These genome segments code for a nucleocapsid protein of 428 amino acids, a glycoprotein precursor protein of 1,138 amino acids and a RNA-dependent RNA polymerase of 2,152 amino acids. In addition, the genome also has other ORFs coding for putative proteins of 34 to 103 amino acids. The encoded proteins have greater than 98% overall similarity with the proteins of Andes virus isolates AH-1 and Chile R123. Among other sequenced Hantavirus, CHI-7913 is more closely related to Sin Nombre virus, with an overall protein similarity of 92%. The characteristics of the encoded proteins of this isolate, such as hydrophobic domains, glycosylation sites, and conserved amino acid motifs shared with other Hantavirus and other members of the Bunyaviridae family, are identified and discussed.

First human isolate of Hantavirus (Andes virus) in the Americas.

We isolated Andes virus (formal name: Andes virus [ANDV], a species in the genus Hantavirus), from serum of an asymptomatic 10-year-old Chilean boy who died 6 days later of hantavirus pulmonary syndrome (HPS). The serum was obtained 12 days after his grandmother died from HPS and 2 days before he became febrile. No hantavirus immunoglobulin (Ig) G or IgM antibodies were detected in the serum sample. After three blind passages, ANDV antigens were detected in Vero E6 cells by immunofluorescence assay and enzyme-linked immunosorbent assay, and ANDV RNA was detected by reverse transcription-polymerase chain reaction. A fragment of the virus genome showed 96.2% nucleotide identity with that of prototype ANDV. To our knowledge, this is the first isolation of any agent of hemorrhagic fever with HPS from a human and the first such isolation of hantavirus before symptoms of that syndrome or HPS began.