Efficacy of rupatadine in reducing the incidence of dengue haemorrhagic fever in patients with acute dengue: A randomised, double blind, placebo-controlled trial
PLoS neglected tropical diseases. 2022;16(6):e0010123
BACKGROUND Rupatadine was previously shown to reduce endothelial dysfunction in vitro, reduced vascular leak in dengue mouse models and to reduce the extent of pleural effusions and thrombocytopenia in patients with acute dengue. Therefore, we sought to determine the efficacy of rupatadine in reducing the incidence of dengue haemorrhagic fever (DHF) in patients with acute dengue. METHODS AND FINDINGS A phase 2, randomised, double blind, placebo controlled clinical trial was carried out in patients with acute dengue in Sri Lanka in an outpatient setting. Patients with ≤3 days since the onset of illness were either recruited to the treatment arm of oral rupatadine 40mg for 5 days (n = 123) or the placebo arm (n = 126). Clinical and laboratory features were measured daily to assess development of DHF and other complications. 12 (9.7%) patients developed DHF in the treatment arm compared to 22 (17.5%) who were on the placebo although this was not significant (p = 0.09, relative risk 0.68, 95% CI 0.41 to 1.08). Rupatadine also significantly reduced (p = 0.01) the proportion of patients with platelet counts <50,000 cells/mm3 and significantly reduced (p = 0.04) persisting vomiting, headache and hepatic tenderness (p<0.0001) in patients. However, there was no difference in the duration of illness and in the proportion of individuals who required hospital admission in both treatment arms. Only 2 patients on rupatadine and 3 patients on the placebo developed shock, while bleeding manifestations were seen in 6 patients on rupatadine and 7 patients on the placebo. CONCLUSIONS Rupatadine appeared to be safe and well tolerated and showed a trend towards a reducing proportion of patients with acute dengue who developed DHF. It usefulness when used in combination with other treatment modalities should be explored. TRIAL REGISTRATION International Clinical Trials Registration Platform: SLCTR/2017/024.
Effect of oseltamivir phosphate versus placebo on platelet recovery and plasma leakage in adults with dengue and thrombocytopenia; a phase 2, multicenter, double-blind, randomized trial
PLoS Neglected Tropical Diseases. 2022;16(1):e0010051
BACKGROUND Thrombocytopenia, bleeding and plasma leakage are major complications of dengue. Activation of endogenous sialidases with desialylation of platelets and endothelial cells may underlie these complications. We aimed to assess the effects of the neuraminidase inhibitor oseltamivir on platelet recovery and plasma leakage in dengue. METHODS We performed a phase 2, double-blind, multicenter, randomized trial in adult dengue patients with thrombocytopenia (<70,000/μl) and a duration of illness ≤ 6 days. Oseltamivir phosphate 75mg BID or placebo were given for a maximum of five days. Primary outcomes were the time to platelet recovery (≥ 100,000/μl) or discharge from hospital and the course of measures of plasma leakage. RESULTS A total of 70 patients were enrolled; the primary outcome could be assessed in 64 patients (31 oseltamivir; 33 placebo). Time to platelet count ≥100,000/μl (n = 55) or discharge (n = 9) were similar in the oseltamivir and placebo group (3.0 days [95% confidence interval, 2.7 to 3.3] vs. 2.9 days [2.5 to 3.3], P = 0.055). The kinetics of platelet count and parameters of plasma leakage (gall bladder thickness, hematocrit, plasma albumin, syndecan-1) were also similar between the groups. DISCUSSION In this trial, adjunctive therapy with oseltamivir phosphate had no effect on platelet recovery or plasma leakage parameters. TRIAL REGISTRATION ISRCTN35227717.
Scoping Review of Crimean-Congo Hemorrhagic Fever (CCHF) Literature and Implications of Future Research
Journal of the College of Physicians and Surgeons--Pakistan : JCPSP. 2019;29(6):563-573
Crimean-Congo hemorrhagic fever (CCHF) is one of the severe forms of high-fatality hemorrhagic fever transmitted by bite of infected ticks or body fluids of infected individuals. Lack of sufficient research and endemic potential of the disease is posing serious threats to public health. The aim of this review was to explore the current status of Crimean-Congo hemorrhagic fever virus (CCHFV) related research and to identify knowledge gaps and the areas that are yet to be explored. An interpretative scoping review methodology was followed to systematically characterize the most recent literature. Literature survey was conducted using electronic databases: PubMed, Scopus, ScienceDirect and Google Scholar. This comprehensive research yielded more than 300 records, but we excluded 100 articles based on our inclusion criteria and duplicates removal. All articles (n=85) that have been published currently were discussed in this scoping review. From a total of 303 documents retrieved, 85 met the criteria. All the documents (case studies, review articles, systematic reviews, meta-analysis, case control studies, cohort studies, randomised control trials, and longitudinal studies) were included in the study. The articles mainly cover different areas such as epidemiology, prevalence, diagnosis, pathogenesis, clinical outcomes, molecular basis, phylogenetics, transmission and treatment of CCHF. Treatment and prevention related knowledge is limited; therefore, future research should focus the development of therapeutics to mitigate the increasing risk of CCHF. Priority future goal should be studies on the molecular basis and treatment of CCHFV infection because several knowledge gaps have been identified in these areas.
Identification of the crucial parameters regarding the efficacy of ribavirin therapy in Crimean-Congo haemorrhagic fever (CCHF) patients: a systematic review and meta-analysis
The Journal of antimicrobial chemotherapy. 2019
OBJECTIVES Recently, ribavirin has been suggested as a therapeutic approach in Crimean-Congo haemorrhagic fever (CCHF) patients; however, there are controversial findings about its efficacy. In the current study, a meta-analysis was systematically performed to assess the effectiveness of ribavirin administration regarding CCHF patient survival and to explore the most important influential parameters for its efficacy. METHODS All of the outcomes of the clinically studied CCHF patients who were treated with ribavirin were included in the meta-analysis. RESULTS Overall, 24 studies met our criteria. Although the studies did not have high quality there was no heterogeneity and publication bias across studies. The results indicated that the administration of ribavirin to CCHF patients significantly decreased the mortality rate (by 1.7-fold) compared with those who did not receive this medication. Furthermore, it was found that the prescription of ribavirin in the initial phase of disease was more effective, and a delay in the start of treatment resulted in a 1.6-fold increase in mortality rate. In addition, interventional therapy resulted in an approximately 2.3-fold reduction in the mortality rate of those who received ribavirin along with corticosteroids compared with those who were treated with ribavirin monotherapy. CONCLUSIONS This meta-analysis reveals that ribavirin should be considered as a crucial antiviral drug in the therapeutic approach used for CCHF patients, especially in early phases of the disease. Additionally, it seems that the administration of corticosteroids alongside ribavirin can play an effective role in alleviation of the disease status, particularly in haemorrhagic phases.
Effect of Helicobacter pylori eradication on platelet count in idiopathic thrombocytopenic purpura: a systematic review and meta- analysis
Journal of Antimicrobial Chemotherapy. 2007;60((2):):237-246.
Background: There is a debate in the recent literature about the effect of Helicobacter pylori eradication on platelet count in patients with idiopathic thrombocytopenic purpura (ITP). In order to clarify this controversial issue, we performed a systematic review with meta-analysis of the available literature. Methods: The meta-analytic comparison was focused on the difference in the platelet count increase between the experimental arm (H. pylori- infected patients who responded to eradication therapy) and each control arm (H. pylori -infected patients who failed to respond to eradication therapy; H. pylori -infected patients who did not receive eradication therapy and H. pylori-negative patients) and was expressed as weighted mean difference (WMD). Moreover, in order to explain the heterogeneity, a meta-regression model was fitted with arm-level covariates. Results: Data involving 788 ITP patients were collected from 17 articles (16 studies with a prospective cohort design and 1 randomized trial). There was a statistically significant difference in the increase in platelet count in patients in whom eradication was successful compared with control groups (WMD, 40.77 × 10(9)/L (95% CI, 20.92-60.63) compared with untreated patients; 52.16 (95% CI, 34.26-70.05) compared with patients who failed eradication and 46.35 (95% CI, 27.79-64.91) compared with H. pylori -negative patients). Moreover, in the meta-regression model, the success of H. pylori eradication was highly significant as an explanatory variable for platelet count increase. Conclusions: Our analysis shows a strict correlation between H. pylori eradication and increase in platelet count. However, due to intrinsic limits in the design of the studies analysed, further evidence from randomized clinical trials is required to confirm the effect of eradication treatment on platelet count.