Prospective, Double-Blind, Concurrent, Placebo-Controlled Clinical Trial of Intravenous Ribavirin Therapy of Hemorrhagic Fever with Renal Syndrome

Huggins, John W.; Hsiang, Chin Min; Cosgriff, Thomas M.; Guang, Mei Ying; Smith, Joseph I.; Wu, Zhen; LeDuc, James W.; Zheng, Zhi-Ming; Meegan, James M.; Wang, Qi Nan; Oland, Dwayne D.; Gui, Xi En; Gibbs, Paul; Yuan, Guang; Zhang, Tian Ming

doi:10.1093/infdis/164.6.1119

Cited by 392 publications

(227 citation statements)

References 11 publications

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“…20,21 However, preliminary in vitro susceptibility testing undertaken by Health Canada's National Microbiology Laboratory and the US Army Medical Research Institute of Infectious Diseases suggests that ribavirin has no demonstrable activity against the SARS-associated coronavirus at concentrations effective for Lassa fever virus and other hemorrhagic fever viruses. 25 In addition, there is no convincing evidence that ribavirin is effective in reducing intensive care admissions, need for ventilatory support, or mortality among adult SARS patients.…”

Section: Discussionmentioning

confidence: 99%

Children Hospitalized With Severe Acute Respiratory Syndrome-Related Illness in Toronto

et al. 2003

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ABSTRACT.Objective. An outbreak of severe acute respiratory syndrome (SARS) occurred in the greater Toronto area between February and June 2003. We describe the clinical, laboratory, and epidemiologic features of children who were admitted to the Hospital for Sick Children, Toronto, with a presumptive diagnosis of suspect or probable SARS.Methods. A prospective investigational study protocol was established for the management of children with a presumptive diagnosis of suspect or probable SARS. All were ultimately classified as having probable SARS, suspect SARS, or another cause on the basis of their epidemiologic exposure, clinical and radiologic features, and results of microbiologic investigations.Results. Twenty-five children were included; 10 were classified as probable SARS and 5 were classified as suspect SARS, and in 10 another cause was identified. The exposure consisted of direct contact with at least 1 adult probable SARS case in 11 children, travel from a World Health Organization-designated affected area in Asia in 9 children, and presence in a Toronto area hospital in which secondary SARS spread had occurred in 5 children. The predominant clinical manifestations of probable cases were fever, cough, and rhinorrhea. With the exception of 1 teenager, none of the children developed respiratory distress or an oxygen requirement, and all made full recoveries. Mild focal alveolar infiltrates were the predominant chest radiograph abnormality. Lymphopenia; neutropenia; thrombocytopenia; and elevated alanine aminotransferase, aspartate aminotransferase, and creatine kinase were present in some cases. Nasopharyngeal swab specimens were negative for the SARS-associated coronavirus by an in-house reverse transcriptase-polymerase chain reaction in all 25 children.Conclusions. Our results indicate that SARS is a relatively mild and nonspecific respiratory illness in previously healthy young children. The presence of fever in conjunction with a SARS exposure history should prompt one to consider SARS as a possible diagnosis in children irrespective of the presence or absence of respiratory symptoms. Reverse-transcriptase polymerase chain reaction analysis of nasopharyngeal specimens seems to be of little utility for the diagnosis of SARS during the early symptomatic phase of this illness in young children. Pediatrics 2003;112:e261-e268. URL: http: //www.pediatrics.org/cgi/content/full/112/4/e261; severe acute respiratory syndrome, reverse-transcriptase polymerase chain reaction, probable SARS, suspect SARS.

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Section: Discussionmentioning

confidence: 99%

Children Hospitalized With Severe Acute Respiratory Syndrome-Related Illness in Toronto

et al. 2003

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“…Some nucleoside analogs have been found to be highly inhibitory in animal models [9] , but ribavirin is the only antiviral agent known to be successful against HTNV infections in clinical trails [10] . However, the utilization of ribavirin is limited by its myelosuppression and toxicity [11][12][13] .…”

Section: Introductionmentioning

confidence: 99%

Efficacy of arbidol on lethal hantaan virus infections in suckling mice and in vitro

et al. 2009

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Aim: Arbidol is an immunomodulator that was first developed in Russia. In this study, we report the antiviral activity of arbidol against Hantaan virus (HTNV) in vitro and in vivo. Methods: The antiviral activity of arbidol in vitro was determined by plaque-forming assay, ranging from 0.5 to 8 μg/mL. To investigate whether arbidol has an antiviral effect in vivo, suckling BALB/c mice infected with HTNV were treated with arbidol at 24 h before infection with a 5, 10 or 20 mg·kg -1 ·d -1 , once per day, for 10 days. On day 12 and 28 post infection (pi), histopathological changes and viral antigen were detected. On days 4, 8, 12, and 16 pi, the viral load of target organs and serum TNF-α levels of arbidol-treated animals were determined. Results: Arbidol was found to have potent inhibitory activity against HTNV when added in vitro before or after viral infection, with a 50% inhibitory concentration (IC 50 ) of 0.9 and 1.2 μg/mL, respectively. The 50% lethal dose (LD 50 ) of arbidol for suckling mice was 78.42 mg·kg -1 ·d -1 . Oral administration of arbidol increased both survival rate and mean time to death (MTD). Treatment with arbidol reduced histopathological changes, decreased viral load and viral antigen levels, and modulated the level of serum TNF-α. Conclusion: Arbidol has the ability to elicit protective antiviral activity against HTNV in vivo and in vitro.

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“…92 Intravenous ribavirin has been further investigated, with success, in the treatment of Lassa fever 93 and HFRS. 94 Both studies demonstrated signifi cant benefi ts of ribavirin in terms of survival and reduction of disease severity. The dosing regimen for intravenous ribavirin consists of a loading dose of 2 g of ribavirin followed by 1 g every 6 hr for 4 days.…”

Section: Imp Dehydrogenase Inhibitors: Ribavirin and Viramidinementioning

confidence: 99%

Existing Influenza Antivirals: Their Mechanisms of Action and Potential in the Face of Avian Influenza

Clercq

2007

Combating the Threat of Pandemic Influenza

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Prospective, Double-Blind, Concurrent, Placebo-Controlled Clinical Trial of Intravenous Ribavirin Therapy of Hemorrhagic Fever with Renal Syndrome

Cited by 392 publications

References 11 publications

Children Hospitalized With Severe Acute Respiratory Syndrome-Related Illness in Toronto

Children Hospitalized With Severe Acute Respiratory Syndrome-Related Illness in Toronto

Efficacy of arbidol on lethal hantaan virus infections in suckling mice and in vitro

Existing Influenza Antivirals: Their Mechanisms of Action and Potential in the Face of Avian Influenza

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