RESUMO
BACKGROUND: Andes virus (ANDV)-related hantavirus cardiopulmonary syndrome (HCPS) has a 35% case fatality rate in Chile and no specific treatment. In an immunomodulatory approach, we evaluated the efficacy of intravenous methylprednisolone for HCPS treatment, through a parallel-group, placebo-controlled clinical trial. METHODS: Patients aged >2 years, with confirmed or suspected HCPS in cardiopulmonary stage, admitted to any of 13 study sites in Chile, were randomized by study center in blocks of 4 with a 1:1 allocation and assigned through sequentially numbered envelopes to receive placebo or methylprednisolone 16 mg/kg/day (≤1000 mg) for 3 days. All personnel remained blinded except the local pharmacist. Infection was confirmed by immunoglobulin M antibodies or ANDV RNA in blood. The composite primary endpoint was death, partial pressure of arterial oxygen/fraction of inspired oxygen ratio ≤55, cardiac index ≤2.2, or ventricular tachycardia or fibrillation within 28 days. Safety endpoints included the number of serious adverse events (SAEs) and quantification of viral RNA in blood. Analysis was by intention to treat. RESULTS: Infection was confirmed in 60 of 66 (91%) enrollees. Fifteen of 30 placebo-treated patients and 11 of 30 methylprednisolone-treated patients progressed to the primary endpoint (P = .43). We observed no significant difference in mortality between treatment groups (P = .41). There was a trend toward more severe disease in placebo recipients at entry. More subjects in the placebo group experienced SAEs (P = .02). There were no SAEs clearly related to methylprednisolone administration, and methylprednisolone did not increase viral load. CONCLUSIONS: Although methylprednisolone appears to be safe, it did not provide significant clinical benefit to patients. Our results do not support the use of methylprednisolone for HCPS. CLINICAL TRIALS REGISTRATION: NCT00128180.
Assuntos
Anti-Inflamatórios/administração & dosagem , Síndrome Pulmonar por Hantavirus/tratamento farmacológico , Metilprednisolona/administração & dosagem , Administração Intravenosa , Adolescente , Adulto , Chile , Método Duplo-Cego , Feminino , Orthohantavírus/genética , Orthohantavírus/isolamento & purificação , Síndrome Pulmonar por Hantavirus/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Resultado do TratamentoRESUMO
In man, infection with South American Andes virus (ANDV) causes hantavirus cardiopulmonary syndrome (HCPS). HCPS due to ANDV is endemic in Southern Chile and much of Argentina and increasing numbers of cases are reported all over South America. A case-fatality rate of about 36% together with the absence of successful antiviral therapies urge the development of a vaccine. Although T-cell responses were shown to be critically involved in immunity to hantaviruses in mouse models, no data are available on the magnitude, specificity and longevity of ANDV-specific memory T-cell responses in patients. Using sets of overlapping peptides in IFN-gamma ELISPOT assays, we herein show in 78 Chilean convalescent patients that Gn-derived epitopes were immunodominant as compared to those from the N- and Gc-proteins. Furthermore, while the relative contribution of the N-specific response significantly declined over time, Gn-specific responses remained readily detectable ex vivo up to 13 years after the acute infection. Tetramer analysis further showed that up to 16.8% of all circulating CD3(+)CD8(+) T cells were specific for the single HLA-B*3501-restricted epitope Gn(465-473) years after the acute infection. Remarkably, Gn(465-473)-specific cells readily secreted IFN-gamma, granzyme B and TNF-alpha but not IL-2 upon stimulation and showed a 'revertant' CD45RA(+)CD27(-)CD28(-)CCR7(-)CD127(-) effector memory phenotype, thereby resembling a phenotype seen in other latent virus infections. Most intriguingly, titers of neutralizing antibodies increased over time in 10/17 individuals months to years after the acute infection and independently of whether they were residents of endemic areas or not. Thus, our data suggest intrinsic, latent antigenic stimulation of Gn-specific T-cells. However, it remains a major task for future studies to proof this hypothesis by determination of viral antigen in convalescent patients. Furthermore, it remains to be seen whether Gn-specific T cells are critical for viral control and protective immunity. If so, Gn-derived immunodominant epitopes could be of high value for future ANDV vaccines.
Assuntos
Antígenos Virais/imunologia , Linfócitos T CD8-Positivos/imunologia , Epitopos de Linfócito T/imunologia , Infecções por Hantavirus/imunologia , Memória Imunológica/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Separação Celular , Chile , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Orthohantavírus/imunologia , Humanos , Epitopos Imunodominantes/imunologiaRESUMO
BACKGROUND: Andes virus (ANDV) infection, which has a case fatality rate of 37% in Chile, often occurs in household clusters and may be transmitted from person to person. METHODS: To determine the incidence and risk factors for additional household cases, we conducted a prospective study among recent household contacts of persons with hantavirus cardiopulmonary syndrome (HCPS) in Chile, including testing of serum for anti-hantavirus antibodies and blood cells for ANDV RNA by reverse-transcription polymerase chain reaction (RT-PCR). RESULTS: We enrolled 76 index case patients and 476 household contacts, of whom 16 (3.4%) developed HCPS; 32.6% of 92 cases occurred in household clusters. The risk of HCPS was 17.6% among sex partners of index case patients, versus 1.2% among other household contacts (P<.001). Person-to-person transmission was definite in 3, probable in 9, and possible in 2 of the 16 additional household case patients. We detected ANDV RNA by RT-PCR in peripheral blood cells 5-15 days before the onset of symptoms or the appearance of anti-hantavirus antibodies. CONCLUSIONS: In recent household contacts of persons with HCPS in Chile, the risk of HCPS was greatest among sex partners. Among the household contacts who developed HCPS, viremia preceded the onset of symptoms and the appearance of anti-hantavirus antibodies by up to 2 weeks.
Assuntos
Busca de Comunicante , Características da Família , Síndrome Pulmonar por Hantavirus/transmissão , Orthohantavírus/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Chile/epidemiologia , Feminino , Orthohantavírus/genética , Orthohantavírus/imunologia , Síndrome Pulmonar por Hantavirus/epidemiologia , Síndrome Pulmonar por Hantavirus/virologia , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , RNA Viral/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Viremia/epidemiologia , Viremia/transmissão , Viremia/virologiaRESUMO
BACKGROUND: Hantaviruses in Europe and Asia cause haemorrhagic fever with renal syndrome and epidemic nephritis (mortality rate <1-15%). New strains of Hantaviruses cause Hantavirus pulmonary syndrome (HPS) from Canada to South America. Andes virus mortality rate is about 30% in Chile. METHOD: Clinical charts of 54 patients were reviewed. RESULTS: Inhalation of aerosolized urine, faeces or saliva of rodents is the principal cause of infection. The incubation period is between 8 and 43 days. The main prodromal symptoms are: myalgias, fever, fatigue, gastrointestinal disorders, dyspnoea, petechiae and coughing. After the 4th day pulmonary oedema, hypotension and renal failure appear. Haemorrhagic disorders may occur. The first laboratory tests presenting alterations are: haemoconcentration, leukocytosis, low platelet count <150 micro/L, and presence of immunoblasts. The treatment is supportive: mechanical ventilation, vasopressor drugs, haemofiltration or haemodialysis, and extracorporeal membrane oxygenation. There is no specific treatment for HPS. Preventive measures must be empathised. CONCLUSION: The principal risk factors for tourists are: accommodation in abandoned or closed up facilities; failure to use indicated pathways when walking in forests; camping outside recommended areas; drinking water from natural sources and fishing in risk areas. The risk of infection for foreign tourists in Chile is low.
Assuntos
Infecções por Hantavirus/epidemiologia , Síndrome Pulmonar por Hantavirus/epidemiologia , Febre Hemorrágica com Síndrome Renal/epidemiologia , Viagem , Zoonoses , Animais , Chile/epidemiologia , Reservatórios de Doenças/veterinária , Orthohantavírus/patogenicidade , Infecções por Hantavirus/transmissão , Síndrome Pulmonar por Hantavirus/transmissão , Febre Hemorrágica com Síndrome Renal/transmissão , Humanos , Estudos Retrospectivos , Fatores de Risco , Doenças dos Roedores/epidemiologia , Doenças dos Roedores/transmissão , RoedoresRESUMO
The potential incubation period from exposure to onset of symptoms was 7-39 days (median 18 days) in 20 patients with a defined period of exposure to Andes virus in a high-risk area. This period was 14-32 days (median 18 days) in 11 patients with exposure for <48 hours.
Assuntos
Síndrome Pulmonar por Hantavirus/transmissão , Orthohantavírus/patogenicidade , Doenças dos Roedores/transmissão , Roedores/virologia , Adolescente , Adulto , Idoso , Animais , Criança , Pré-Escolar , Chile , Exposição Ambiental , Feminino , Síndrome Pulmonar por Hantavirus/diagnóstico , Síndrome Pulmonar por Hantavirus/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças dos Roedores/virologia , Fatores de TempoRESUMO
BACKGROUND: This case report describes the unusual appearance of simultaneous left, primary, spontaneous pneumothorax in identical twins in Temuco, Chile. CASE REPORT: Bullectomy and abrasive pleurodesis by video-assisted thoracoscopy was performed on one of the twins. The second twin was observed conservatively. Both were nonsmokers and had normal alfa 1 antitripsine values and identical human leukocyte antigen haplotypes. Contralateral pneumothorax occurred in the twin treated by video-assisted thoracoscopic surgery after three years, and ipsilateral pneumothorax occurred in the second twin after two years. CONCLUSIONS: Neither the conservative nor the invasive treatment by video-assisted thoracoscopic surgery avoided recurrence. The inheritance of familial spontaneous pneumothorax is not well known. Autosomal dominant and recessive inheritance were proposed, but not proven, and an association with human leukocyte antigen haplotypes is uncertain. Further studies are needed to know the mode of inheritance.
Assuntos
Doenças em Gêmeos , Pneumotórax/diagnóstico , Adolescente , Lateralidade Funcional , Humanos , Masculino , Pneumotórax/terapia , Resultado do Tratamento , Gêmeos MonozigóticosRESUMO
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.
Assuntos
Anticorpos Antivirais/sangue , Infecção Hospitalar/transmissão , Síndrome Pulmonar por Hantavirus/transmissão , Pessoal de Saúde , Orthohantavírus/imunologia , Adulto , Chile/epidemiologia , Surtos de Doenças , Feminino , Humanos , Masculino , Estudos SoroepidemiológicosRESUMO
An epidemiologic and seroprevalence survey was conducted (n=830) to assess the proportion of persons exposed to hantavirus in IX Region Chile, which accounts for 25% of reported cases of hantavirus cardiopulmonary syndrome. This region has three geographic areas with different disease incidences and a high proportion of aboriginals. Serum samples were tested for immunoglobulin (Ig) G antibodies by enzyme-linked immunosorbent assay against Sin Nombre virus N antigen by strip immunoblot assay against Sin Nombre, Puumala, Río Mamoré, and Seoul N antigens. Samples from six patients were positive for IgG antibodies reactive with Andes virus; all patients lived in the Andes Mountains. Foresting was also associated with seropositivity; but not sex, age, race, rodent exposure, or farming activities. Exposure to hantavirus varies in different communities of IX Region. Absence of history of pneumonia or hospital admission in persons with specific IgG antibodies suggests that infection is clinically inapparent.
Assuntos
Infecções por Hantavirus/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Chile/epidemiologia , Feminino , Orthohantavírus/imunologia , Orthohantavírus/isolamento & purificação , Infecções por Hantavirus/imunologia , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
BACKGROUND: Thirty six cases of clinical Hantavirus Cardiopulmonary Syndrome occurred in the IX Region of Chile. Most of these patients were young males, farm or timber workers, who lived near the Andes Mountain chain. AIM: To conduct an epidemiological and serosurvey study to determine the seroprevalence of IgG antibodies against Hantavirus in the general adult population living in rural and urban areas of 10 endemic communities of the IX region of Chile. MATERIAL AND METHODS: A total of 400 subjects were included, 40 of each community, 20 rural residents and 20 urban residents, 20 males and 20 females. RESULTS: Seroprevalence was 7.5% in Melipeuco, 5.0% in Lonquimay, 2.5% in Curacautin, 2.5% in Pucón and 0.0% in the remaining communities. Seroprevalence was higher in rural population (2.5%) than in the urban areas (1%). All seropositive subjects worked in farms or forests and observed rodents near their homes or working places. Females were affected the same as males and no differences were observed between Chilean natives and Hispanics. CONCLUSIONS: Prevalence of Hantavirus antibodies correlated with the geographic zone (Andes Mountain chain), overgrowth of wild rodents and exposure to rodent-infested environments.
Assuntos
Anticorpos Antivirais/sangue , Síndrome Pulmonar por Hantavirus/epidemiologia , Imunoglobulina G/sangue , Orthohantavírus/imunologia , Adolescente , Adulto , Animais , Chile/epidemiologia , Ensaio de Imunoadsorção Enzimática , Métodos Epidemiológicos , Feminino , Síndrome Pulmonar por Hantavirus/sangue , Síndrome Pulmonar por Hantavirus/diagnóstico , Humanos , Immunoblotting , Masculino , Pessoa de Meia-Idade , Roedores , População Rural , População UrbanaRESUMO
La neumonía tuberculosa, es una forma de presentación infrecuente de la tuberculosis pulmonar, cuyas características clínicas inducen al diagnóstico erróneo de neumonía bacteriana, especialmente al diagnóstico de neumonía neumocócica. Presentamos el cuadro clínico de 5 pacientes entre 15 y 57 años con el diagnóstico de neumonía tuberculosa. Todos ellos consultaron por fiebre mayor de 38ºC de inicio súbito, con calofríos, dolor tipo puntada de costado y tos irritativa o con escasa expectoración mucosa. Al examen físico se encontró en todos ellos un típico síndrome de condensación. La radiografía de tórax reveló una condensación segmentaria o lobar de predominio en los lóbulos inferiores. El hematocrito oscilo entre 28 y 35 por ciento. Los glóbulos blancos entre 6.000 y 14.000/mm3, sin desviación a izquierda y la VHS fluctuó entre 58 y 122 mm/h. Todos recibieron hemocultivos y cultivos de expectoración negativos. Las baciloscopias de expectoración fueron negativas. Todos recibieron inicialmente penicilina durante una semana sin respuesta, posteriormente recibieron tetraciclina o macrólidos, sin mejoría. La fibrobroncoscopia fue normal en todos y en tres de ellos las baciloscopias de lavado broncoalveolar resultaron positivas. La baciloscopia post broncoscopia resultó positiva en los otros dos enfermos. Con tratamiento antituberculoso todos mejoraron
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Erros de Diagnóstico , Pneumonia Pneumocócica/diagnóstico , Tuberculose Pulmonar/diagnóstico , Antibióticos Antituberculose/uso terapêutico , Radiografia Torácica , Sinais e Sintomas , Tuberculose Pulmonar/tratamento farmacológicoRESUMO
El estudio etiológico de la neumonías se puede abordar con la tinción de Gram de la expectoración que aporta valiosa información inicial especialmente en las neumonías neumocócicas. Además es rápida y de bajo costo. El cultivo en cambio, no tiene utilidad por su alta proporción de falsos positivos y de falsos negativos. El hemocultivo debe realizarse, porque aunque tiene bajo rendimiento, cuando es positivo, aporta el germen causal. La punción aspirativa transtraqueal permite obtener muestras para Gram y cultivo con mejor rendimiento que la expectoración. La punción pulmonar presenta pocas complicaciones y permite un diagnóstico etiológico especialmente en las neumonías complejas, sin embargo, no debe ser un método de rutina. La broncoscopía aspirativa facilita la obtención de muestras cerca del foco infeccioso pero arrastra gérmenes del tracto respiratorio alto y frecuentementemente los cultivos no representan el germen causal. Para evitar este problema se usan catéteres con cepillo protegido con los que se obtienen muestras más representativas. En los pacientes intubados o traqueotomizados se debe obtener muestra de aspiración traqueal que aporta información valiosa y que se compara bastante favorablemente con el uso de otra técnicas más complejas. La elección de las técnicas y su interpretación son materia del juicio clínico y del conocimiento del médico