Ribavirin for treating Crimean Congo haemorrhagic fever

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infectious disease 2 infectiousdiseases
ribavirin 159 infectiousdiseasesdrugs
Lassa fever 1 infectiousdiseases
hepatitis C 2 infectiousdiseases

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ribavirin 611 reduce mortality. There is uncertainty and controversy about treating CCHF with the antiviral drug ribavirin .ObjectivesTo assess the effects of ribavirin for treating people with Crimean Congo haemorrhagic fever.Search
ribavirin 656 controversy about treating CCHF with the antiviral drug ribavirin.ObjectivesTo assess the effects of ribavirin for treating people with Crimean Congo haemorrhagic fever.Search methodsWe searched the Cochrane Infectious
ribavirin 1351 obtained further studies from these sources.Selection criteriaWe evaluated studies assessing the use of ribavirin in people with suspected or confirmed Crimean Congo haemorrhagic fever. We included randomised control
ribavirin 2219 studies with critical risk of bias for the primary outcome, as these are often cited to support using ribavirin .Main resultsFor the main effects analysis, five studies met our inclusion criteria: one RCT with 136
ribavirin 2534 studies with critical risk of bias, where none had attempted to control for confounding.We do not know if ribavirin reduces mortality (1 RCT; RR 1.13, 95% confidence interval (CI) 0.29 to 4.32; 136 participants; very
ribavirin 2791 studies; RR 0.72, 95% CI 0.41 to 1.28; 549 participants; very low-certainty evidence). We do not know if ribavirin reduces the length of stay in hospital (1 RCT: mean difference (MD) 0.70 days, 95% CI -0.39 to 1.79;
ribavirin 3336 anaemia and a need to discontinue treatment), we do not know whether there is an increased risk with ribavirin in people with CCHF as data are insufficient.We do not know if adding ribavirin to early supportive
ribavirin 3416 increased risk with ribavirin in people with CCHF as data are insufficient.We do not know if adding ribavirin to early supportive care improves outcomes. One non-randomized study assessed mortality in people receiving
ribavirin 3534 supportive care improves outcomes. One non-randomized study assessed mortality in people receiving ribavirin and supportive care within four days or less from symptom onset compared to after four days since symptom
ribavirin 3726 four days since symptom onset: mortality was lower in the group receiving early supportive care and ribavirin , but it is not possible to distinguish between the effects of ribavirin and early supportive medical
ribavirin 3798 receiving early supportive care and ribavirin, but it is not possible to distinguish between the effects of ribavirin and early supportive medical care alone.In the subsidiary analysis, 18 studies compared people receiving
ribavirin 3913 early supportive medical care alone.In the subsidiary analysis, 18 studies compared people receiving ribavirin with those not receiving ribavirin. All had a critical risk of bias due to confounding, reflected in
ribavirin 3948 alone.In the subsidiary analysis, 18 studies compared people receiving ribavirin with those not receiving ribavirin . All had a critical risk of bias due to confounding, reflected in the mortality point estimates favouring
ribavirin 4064 had a critical risk of bias due to confounding, reflected in the mortality point estimates favouring ribavirin .Authors' conclusionsWe do not know if ribavirin is effective for treating Crimean Congo haemorrhagic
ribavirin 4112 reflected in the mortality point estimates favouring ribavirin.Authors' conclusionsWe do not know if ribavirin is effective for treating Crimean Congo haemorrhagic fever. Non-randomized studies are often cited as
ribavirin 4429 haemorrhagic feverWhat is the aim of this review?The aim of this Cochrane review is to find out if ribavirin is an effective treatment for Crimean Congo haemorrhagic fever. Cochrane researchers collected and analysed
ribavirin 4836 the limitations of the evidence.Key messagesThere is insufficient reliable evidence to show whether ribavirin is effective in treating Crimean Congo haemorrhagic fever. A randomised clinical trial could help answer
ribavirin 5530 to treat CCHF. It is widely available and is normally taken by mouth. There is debate over whether ribavirin is needed to treat CCHF; some argue that it is an effective treatment, or helps if given early, whilst
ribavirin 5870 from the drug itself.Overall, the study designs did not take into account factors other than taking ribavirin that could result in better outcomes in the intervention group, including how ill the patient was when
ribavirin 6078 when diagnosed, or when good supportive medical care was started. This made any association between ribavirin and lower mortality problematic.We found five studies that took into account important factors that
ribavirin 6260 account important factors that could confound the risk of dying with whether or not a patient received ribavirin . These include how sick the study participants were, what other care they received, and how long after
ribavirin 6517 All included studies were conducted in Turkey and Iran, and compared people with CCHF who received ribavirin and supportive care to those who received supportive care alone. We looked at five different outcomes
ribavirin 6641 care to those who received supportive care alone. We looked at five different outcomes relating to ribavirin use in CCHF, and found that there is insufficient reliable evidence to determine whether ribavirin is
ribavirin 6740 ribavirin use in CCHF, and found that there is insufficient reliable evidence to determine whether ribavirin is effective.How up to date is the review?The review authors searched for studies that had been published
ribavirin 6946 published up to 16 October 2017.Summary of findings for the main comparisonRibavirin compared to no ribavirin for Crimean Congo haemorrhagic feverPatient or population: people diagnosed with suspected or confirmed
ribavirin 7121 diagnosed with suspected or confirmed Crimean Congo haemorrhagic feverSetting: globalIntervention: ribavirin Comparison: no ribavirinOutcomesAnticipated absolute effects* (95% CI)Relative effect (95% CI)Number
ribavirin 7145 suspected or confirmed Crimean Congo haemorrhagic feverSetting: globalIntervention: ribavirinComparison: no ribavirin OutcomesAnticipated absolute effects* (95% CI)Relative effect (95% CI)Number of participants (studies)Certainty
ribavirin 7310 effect (95% CI)Number of participants (studies)Certainty of the evidence (GRADE)CommentsRisk with no ribavirin Risk with ribavirinMortality56 per 100063 per 1000(16 to 240)RR 1.13(0.29 to 4.32)136(1 RCT)1⊕⊖⊖⊖VERY
ribavirin 7329 CI)Number of participants (studies)Certainty of the evidence (GRADE)CommentsRisk with no ribavirinRisk with ribavirin Mortality56 per 100063 per 1000(16 to 240)RR 1.13(0.29 to 4.32)136(1 RCT)1⊕⊖⊖⊖VERY LOW2,3-Length
ribavirin 13603 ([127]; [15]; [5]), although this has been debated ([13]; [60]). One such idea is that administration of ribavirin early in the disease, when it appears to be at its most effective, may be a promising approach ([5];
ribavirin 14238 and deranged liver function ([123]). Two previous systematic reviews have shown no clear benefit of ribavirin in people with CCHF, although the available evidence is limited mainly to confounded non-randomized
ribavirin 15193 countries such as South Africa ([121]), India ([136]), and Pakistan ([137]) recommend prompt treatment with ribavirin following diagnosis of CCHF. However, these recommendations for management are not based on a robust
ribavirin 15486 necessary to treat mild cases of the disease ([7]). Questions remain about the overall benefits of ribavirin , how long after the onset of symptoms it is most effective, and whether it is more or less effective
ribavirin 15698 in severe cases ([124]; [5]; [132]).Why it is important to do this reviewThe controversy surrounding ribavirin use and the benefits of a widely-available treatment for CCHF mean an up-to-date review of the existing
ribavirin 15886 up-to-date review of the existing evidence is required. There are mixed views on whether to treat CCHF with ribavirin , given the uncertainty about the balance between potential but unproven benefit and known risks of the
ribavirin 16083 known risks of the drug ([13]). It is therefore important to use the data available to address whether ribavirin reduces the number of deaths from a lethal disease, whilst assessing the possibility of harm from serious,
ribavirin 16268 possibility of harm from serious, life-threatening adverse effects.ObjectivesTo assess the effects of ribavirin for treating people with Crimean Congo haemorrhagic fever (CCHF).MethodsCriteria for considering studies
ribavirin 16545 of study:Randomized controlled trials (RCTs), quasi-RCTs, and non-randomized controlled studies of ribavirin compared to no ribavirin; also studies comparing early versus late administration of ribavirinCohort
ribavirin 16570 controlled trials (RCTs), quasi-RCTs, and non-randomized controlled studies of ribavirin compared to no ribavirin ; also studies comparing early versus late administration of ribavirinCohort studies with ribavirin compared
ribavirin 16640 studies of ribavirin compared to no ribavirin; also studies comparing early versus late administration of ribavirin Cohort studies with ribavirin compared to no ribavirin, and studies comparing early versus late administration
ribavirin 16669 ribavirin; also studies comparing early versus late administration of ribavirinCohort studies with ribavirin compared to no ribavirin, and studies comparing early versus late administration of ribavirin (prospective
ribavirin 16694 comparing early versus late administration of ribavirinCohort studies with ribavirin compared to no ribavirin , and studies comparing early versus late administration of ribavirin (prospective and retrospective,
ribavirin 16763 with ribavirin compared to no ribavirin, and studies comparing early versus late administration of ribavirin (prospective and retrospective, with more than 10 participants).Case-control studies with ribavirin
ribavirin 16863 ribavirin (prospective and retrospective, with more than 10 participants).Case-control studies with ribavirin compared to no ribavirin, and studies comparing early versus late administration of ribavirinTypes of
ribavirin 16888 and retrospective, with more than 10 participants).Case-control studies with ribavirin compared to no ribavirin , and studies comparing early versus late administration of ribavirinTypes of participantsChildren or
ribavirin 16957 with ribavirin compared to no ribavirin, and studies comparing early versus late administration of ribavirin Types of participantsChildren or adults of any age with CCHF confirmed with a laboratory test (immunoglobulin
ribavirin 17192 polymerase chain reaction (PCR))Types of interventionsInterventionRibavirin (intravenous (IV) or oral)Early ribavirin (as defined in identified studies)ControlSupportive care onlyLate ribavirin (as defined by study authors)We
ribavirin 17268 (intravenous (IV) or oral)Early ribavirin (as defined in identified studies)ControlSupportive care onlyLate ribavirin (as defined by study authors)We accepted co-interventions as long as the indication for the co-intervention
ribavirin 19253 ClinicalTrials.gov (clinicaltrials.gov/ct2/home) for trials in progress, up to 16 October 2017, using " ribavirin " and "Crimean Congo haemorrhagic fever" or "CCHF" as search terms.Searching other resourcesWe searched
ribavirin 21199 (days)Transfusion of blood productsSerious adverse eventsTime since onset of symptoms (days) to treatment with ribavirin or supportive care onlyAssessment of risk of bias in included studiesTwo review authors assessed the
ribavirin 22261 assessment of confounding we considered length of time from onset of symptoms to receiving medical care or ribavirin , severity of disease, historical controls rather than contemporary controls, and quality of supportive
ribavirin 24837 amount of missing data from an analysis looking at the added benefit of corticosteroid use as well as ribavirin ([5]). This occurred because the number of participants included in the analysis did not tally with
ribavirin 25372 the results stratified by severity of diease. As the missing data did not affect results relating to ribavirin and mortality, we did not classify the study as being at critical risk of bias.Assessment of heterogeneityWe
ribavirin 27827 residual confounding due to time from onset of symptoms to presentation to hospital/administration of ribavirin , and the fact that the study analysed severely-ill patients with gastro-intestinal haemorrhage "per
ribavirin 28738 heterogeneity occurred we intended to perform subgroup analyses of the results, to assess whether the effect of ribavirin was influenced by any of the following factors:Severity of symptoms: severe, moderate, mildDuration
ribavirin 30470 CCHF, and two reported on outcomes not included in our review. Fifty-one studies did not report on ribavirin for treating CCHF, nine had no comparator arm and 27 were single-case reports. Fifty were cohort studies
ribavirin 30964 criteria.Included studiesSee Characteristics of included studies.We include 23 studies that tested the use of ribavirin in people with CCHF, with the outcomes of mortality, length of hospital stay, and requirement for transfusion.Main
ribavirin 31750 primary analysis and how controls were selected varied. [6] used historical controls from a period when ribavirin was unavailable. [5] selected controls based on clinical criteria including time from onset of symptoms
ribavirin 31905 on clinical criteria including time from onset of symptoms to diagnosis or contraindication to oral ribavirin . [12] compared administration of ribavirin given early in the disease to late in the disease. [3] used
ribavirin 31948 onset of symptoms to diagnosis or contraindication to oral ribavirin. [12] compared administration of ribavirin given early in the disease to late in the disease. [3] used a retrospective design that matched 10 participants
ribavirin 32083 disease to late in the disease. [3] used a retrospective design that matched 10 participants who received ribavirin to 40 controls that did not, using various clinical and physiological parameters.SettingFour out of
ribavirin 32808 only, using either Ig enzyme-linked immunosorbent assay (ELISA) or PCR to verify.InterventionDoses of ribavirin differed between studies. [6] described weight-based prescribing (30 mg/kg initial loading dose; 15
ribavirin 33254 in the ‘Characteristics of included studies' table. All studies in this analysis administered oral ribavirin .ComparatorsNone of the participants in the comparator groups received ribavirin for the comparison of
ribavirin 33334 analysis administered oral ribavirin.ComparatorsNone of the participants in the comparator groups received ribavirin for the comparison of ribavirin versus no ribavirin. One study ([12]) was included in the main effects
ribavirin 33366 ribavirin.ComparatorsNone of the participants in the comparator groups received ribavirin for the comparison of ribavirin versus no ribavirin. One study ([12]) was included in the main effects analysis that offered a comparison
ribavirin 33386 participants in the comparator groups received ribavirin for the comparison of ribavirin versus no ribavirin . One study ([12]) was included in the main effects analysis that offered a comparison of early versus
ribavirin 33503 study ([12]) was included in the main effects analysis that offered a comparison of early versus late ribavirin ; all those in the comparator arm received ribavirin after four days.Length of follow-upNo studies specified
ribavirin 33555 that offered a comparison of early versus late ribavirin; all those in the comparator arm received ribavirin after four days.Length of follow-upNo studies specified a length of follow-up. Instead, they relied
ribavirin 34531 retrospective cohort studies. One study used a cohort of patients treated before the availability of ribavirin as a control arm. ([18]).SettingIn those studies included in the descriptive analysis 12 were conducted
ribavirin 34986 are outlined in Appendix 2.ParticipantsIn the subsidiary descriptive analysis for the comparison of ribavirin versus no ribavirin an additional 1214 participants in 10 studies at critical risk of bias were analysed.In
ribavirin 35006 Appendix 2.ParticipantsIn the subsidiary descriptive analysis for the comparison of ribavirin versus no ribavirin an additional 1214 participants in 10 studies at critical risk of bias were analysed.In the subsidiary
ribavirin 35180 of bias were analysed.In the subsidiary descriptive analysis for the comparison of early versus late ribavirin an additional 431 participants in 4 studies received either early or late ribavirin.InterventionFor
ribavirin 35264 early versus late ribavirin an additional 431 participants in 4 studies received either early or late ribavirin .InterventionFor the comparison of ribavirin versus no ribavirin doses were broadly the same; we give
ribavirin 35308 participants in 4 studies received either early or late ribavirin.InterventionFor the comparison of ribavirin versus no ribavirin doses were broadly the same; we give full details in the ‘Characteristics of included
ribavirin 35328 studies received either early or late ribavirin.InterventionFor the comparison of ribavirin versus no ribavirin doses were broadly the same; we give full details in the ‘Characteristics of included studies' table.
ribavirin 35490 the ‘Characteristics of included studies' table. Most studies in this analysis administered oral ribavirin .For the comparison of early versus late ribavirin, participants received ribavirin according to the
ribavirin 35540 table. Most studies in this analysis administered oral ribavirin.For the comparison of early versus late ribavirin , participants received ribavirin according to the study author's definitions of early versus late. Studies
ribavirin 35573 administered oral ribavirin.For the comparison of early versus late ribavirin, participants received ribavirin according to the study author's definitions of early versus late. Studies used different cut-off time
ribavirin 35730 early versus late. Studies used different cut-off time points for the definition of early care with ribavirin , either less than three days since onset of symptoms ([19]; [20]), less than four days since onset of
ribavirin 35949 symptoms ([12]) or less than five days since the onset of symptoms ([16]; [21]). 114 participants received ribavirin less than three days from the onset of symptoms, 97 received ribavirin after 3 days since the onset
ribavirin 36020 [21]). 114 participants received ribavirin less than three days from the onset of symptoms, 97 received ribavirin after 3 days since the onset of symptoms. One hundred and thirty participants received ribavirin less
ribavirin 36117 received ribavirin after 3 days since the onset of symptoms. One hundred and thirty participants received ribavirin less than five days from onset of symptoms with 90 participants receiving ribavirin after this time
ribavirin 36201 participants received ribavirin less than five days from onset of symptoms with 90 participants receiving ribavirin after this time point.ComparatorsOf those studies covered by the descriptive analysis, four studies
ribavirin 38402 confounding by severity. Time from onset of symptoms to diagnosis was addressed by not prescribing ribavirin to anyone with more than seven days history of symptoms (Table 3). One historically-controlled cohort
ribavirin 38962 cohort study ([12]) stratified mortality outcome by time from onset of symptoms to administration of ribavirin (Table 5). This study performed a regression analysis, although this was designed to identify predictive
ribavirin 40865 interventionsWe judged all studies to be at low risk of bias, as the doses and methods of administration of ribavirin were well-defined.Bias due to deviations from intended interventionsWe judged all studies to be at low
ribavirin 41325 missing data were related to numbers of participants receiving co-administration of corticosteroids with ribavirin . We judged the balance of missing data across groups as unclear, as there was insufficient documentation
ribavirin 41724 investigators will have been aware of the intervention status of the participants (if they received ribavirin or not), none of the measured outcomes were subjective and thus prone to bias.Bias in the selection
ribavirin 42826 groups.Effects of interventionsSee: Summary of findings for the main comparison Ribavirin versus no ribavirin for Crimean Congo haemorrhagic fever; Summary of findings 2 Early versus late supportive care plus ribavirin
ribavirin 42935 for Crimean Congo haemorrhagic fever; Summary of findings 2 Early versus late supportive care plus ribavirin for Crimean Congo haemorrhagic feverOur main effects analysis included one RCT and four non-randomized
ribavirin 43239 used in a subsidiary descriptive analysis for our primary outcome of mortality.Ribavirin versus no ribavirin MortalityOne RCT and three non-randomized studies were included that compared the effect on mortality
ribavirin 43353 ribavirinMortalityOne RCT and three non-randomized studies were included that compared the effect on mortality of ribavirin and no ribavirin in participants with CCHF (Figure 3).Figure 3.Forest plot of Ribavirin versus no ribavirin,
ribavirin 43370 three non-randomized studies were included that compared the effect on mortality of ribavirin and no ribavirin in participants with CCHF (Figure 3).Figure 3.Forest plot of Ribavirin versus no ribavirin, outcome:
ribavirin 43461 ribavirin and no ribavirin in participants with CCHF (Figure 3).Figure 3.Forest plot of Ribavirin versus no ribavirin , outcome: mortality.RCTOne RCT of 136 participants ([14]) found no statistically significant effect
ribavirin 43591 mortality.RCTOne RCT of 136 participants ([14]) found no statistically significant effect in favour of either ribavirin or no ribavirin (RR 1.13, 95% CI 0.29 to 4.32; Analysis 1.1).Non-randomized studiesOne mixed retrospective
ribavirin 43607 136 participants ([14]) found no statistically significant effect in favour of either ribavirin or no ribavirin (RR 1.13, 95% CI 0.29 to 4.32; Analysis 1.1).Non-randomized studiesOne mixed retrospective and prospective
ribavirin 43931 in 103 mild cases and risk ratios were therefore not calculable. In 152 moderate cases (subgroup 2) ribavirin reduced mortality (RR 0.09, 95% CI 0.02 to 0.50). In 26 severe patients no effect of ribavirin on mortality
ribavirin 44026 (subgroup 2) ribavirin reduced mortality (RR 0.09, 95% CI 0.02 to 0.50). In 26 severe patients no effect of ribavirin on mortality was seen (RR 0.79, 95% CI 0.44 to 1.41; Analysis 1.2, Figure 4). The two participants in
ribavirin 44203 Figure 4). The two participants in the severe disease strata control group were unable to take oral ribavirin due to gastro-intestinal bleeding, despite an intention to treat them with ribavirin.Figure 4.Forest
ribavirin 44288 unable to take oral ribavirin due to gastro-intestinal bleeding, despite an intention to treat them with ribavirin .Figure 4.Forest plot of comparison: 1 Ribavirin versus no ribavirin, outcome: 1.2 Mortality stratified
ribavirin 44356 an intention to treat them with ribavirin.Figure 4.Forest plot of comparison: 1 Ribavirin versus no ribavirin , outcome: 1.2 Mortality stratified by severity of disease ([5]).One cohort study with a historical control
ribavirin 44663 disease and time from onset of symptoms ([6]). This study showed no statistically significant benefit of ribavirin on mortality (RR 0.60, 95% CI 0.26 to 1.38; Analysis 1.1)One retrospective matched cohort study of 50
ribavirin 44835 retrospective matched cohort study of 50 participants used a matched design where those who received ribavirin were randomly matched to a control group with similar baseline characteristics ([3]). In this study
ribavirin 45542 studies, this further decreases our confidence in the effect estimate.In summary, it is uncertain whether ribavirin reduces mortality, because the certainty of the evidence is very low from both the RCT and the non-randomized
ribavirin 45833 (retrospective matched cohort design) and one RCT met our inclusion criteria and evaluated the effect of ribavirin on length of hospital stay in participants with CCHF receiving ribavirin or not ([14]; [3]; Analysis
ribavirin 45906 and evaluated the effect of ribavirin on length of hospital stay in participants with CCHF receiving ribavirin or not ([14]; [3]; Analysis 1.3; Figure 5).Figure 5.Forest plot of ribavirin versus no ribavirin, outcome:
ribavirin 45983 participants with CCHF receiving ribavirin or not ([14]; [3]; Analysis 1.3; Figure 5).Figure 5.Forest plot of ribavirin versus no ribavirin, outcome: length of hospital stay (days).RCT[14] showed no effect of ribavirin on
ribavirin 46003 receiving ribavirin or not ([14]; [3]; Analysis 1.3; Figure 5).Figure 5.Forest plot of ribavirin versus no ribavirin , outcome: length of hospital stay (days).RCT[14] showed no effect of ribavirin on the length of hospital
ribavirin 46082 ribavirin versus no ribavirin, outcome: length of hospital stay (days).RCT[14] showed no effect of ribavirin on the length of hospital stay in days (MD 0.70, 95% CI -0.39 to 1.79; 136 participants; Analysis 1.3).Non-randomized
ribavirin 46241 95% CI -0.39 to 1.79; 136 participants; Analysis 1.3).Non-randomized studies[3] showed no effect of ribavirin on the length of hospital stay in days (MD -0.80, 95% CI -2.70 to 1.10; 50 participants; Analysis 1.3).In
ribavirin 46384 days (MD -0.80, 95% CI -2.70 to 1.10; 50 participants; Analysis 1.3).In summary, we do not know if ribavirin reduces the length of stay in hospital, as the certainty of the evidence is very low (Table 1).Requirement
ribavirin 46556 the evidence is very low (Table 1).Requirement for transfusionOne included RCT compared the effect of ribavirin with no ribavirin on the need for transfusion of blood products in participants with CCHF ([14]). There
ribavirin 46574 low (Table 1).Requirement for transfusionOne included RCT compared the effect of ribavirin with no ribavirin on the need for transfusion of blood products in participants with CCHF ([14]). There was no statistically
ribavirin 47069 reported on adverse events leading to discontinuation of treatment. One participant among 44 who received ribavirin and corticosteroids discontinued ribavirin due to elevated amylase levels ([5]).Serious adverse eventsNo
ribavirin 47112 discontinuation of treatment. One participant among 44 who received ribavirin and corticosteroids discontinued ribavirin due to elevated amylase levels ([5]).Serious adverse eventsNo studies in the primary analysis reported
ribavirin 47271 adverse eventsNo studies in the primary analysis reported on adverse events.Timing of administration of ribavirin : early versus late ribavirinMortalityOne non-randomized study (retrospective cohort) was included that
ribavirin 47300 primary analysis reported on adverse events.Timing of administration of ribavirin: early versus late ribavirin MortalityOne non-randomized study (retrospective cohort) was included that addressed the timing of administration
ribavirin 47426 non-randomized study (retrospective cohort) was included that addressed the timing of administration of ribavirin alongside supportive care and mortality ([12]).[12] outlined an association between reduced mortality
ribavirin 47580 ([12]).[12] outlined an association between reduced mortality in those who received supportive care and ribavirin less than four days since the onset of any symptoms compared to those receiving supportive care and
ribavirin 47690 less than four days since the onset of any symptoms compared to those receiving supportive care and ribavirin after four days (RR 0.39, 95% CI 0.16 to 0.95; 63 participants; Analysis 2.1; Figure 6).Figure 6.Forest
ribavirin 47827 95% CI 0.16 to 0.95; 63 participants; Analysis 2.1; Figure 6).Figure 6.Forest plot early versus late ribavirin , outcome: mortality in early versus late ribavirin.Whilst an association was seen between early supportive
ribavirin 47878 Figure 6).Figure 6.Forest plot early versus late ribavirin, outcome: mortality in early versus late ribavirin .Whilst an association was seen between early supportive care and ribavirin and reduced mortality in
ribavirin 47953 mortality in early versus late ribavirin.Whilst an association was seen between early supportive care and ribavirin and reduced mortality in one included study at serious risk of bias, we are uncertain if early ribavirin
ribavirin 48058 ribavirin and reduced mortality in one included study at serious risk of bias, we are uncertain if early ribavirin is more effective than late ribavirin in treating CCHF. Separating the effect of early presentation
ribavirin 48096 included study at serious risk of bias, we are uncertain if early ribavirin is more effective than late ribavirin in treating CCHF. Separating the effect of early presentation to hospital, early diagnosis and early
ribavirin 48248 early presentation to hospital, early diagnosis and early supportive care from the effect of early ribavirin treatment is very difficult without an adequately-powered randomised study.Subsidiary descriptive analysesRibavirin
ribavirin 48384 difficult without an adequately-powered randomised study.Subsidiary descriptive analysesRibavirin versus no ribavirin In the subsidiary descriptive analysis we explored the effect of confounding on the effect estimates
ribavirin 48498 the subsidiary descriptive analysis we explored the effect of confounding on the effect estimates for ribavirin versus no ribavirin. We included 10 studies at critical risk of bias that reported mortality outcomes.
ribavirin 48518 descriptive analysis we explored the effect of confounding on the effect estimates for ribavirin versus no ribavirin . We included 10 studies at critical risk of bias that reported mortality outcomes. We established a
ribavirin 48932 studies with a critical risk of bias, the point estimates shows an effect skewed towards benefit for ribavirin (1 RCT; RR 1.13, 95% CI 0.29 to 4.32; 136 participants; 3 non-randomized studies at serious risk of
ribavirin 49746 heterogeneity and inconsistency between studies.Figure 7.Forest plot of subsidiary descriptive analysis: ribavirin versus no ribavirin, outcome: mortality.Early versus late supportive care with ribavirinIn the subsidiary
ribavirin 49766 inconsistency between studies.Figure 7.Forest plot of subsidiary descriptive analysis: ribavirin versus no ribavirin , outcome: mortality.Early versus late supportive care with ribavirinIn the subsidiary descriptive analysis
ribavirin 49835 analysis: ribavirin versus no ribavirin, outcome: mortality.Early versus late supportive care with ribavirin In the subsidiary descriptive analysis of early versus late ribavirin, we explored the effect of confounding
ribavirin 49904 versus late supportive care with ribavirinIn the subsidiary descriptive analysis of early versus late ribavirin , we explored the effect of confounding of the effect estimates. We included four studies at critical
ribavirin 50264 8.Forest plot of comparison: 4 Subsidiary descriptive analysis: early versus late supportive care with ribavirin , outcome: 4.1 Mortality stratified by study type.Our subsidiary descriptive analysis showed an association
ribavirin 50416 study type.Our subsidiary descriptive analysis showed an association between early supportive care with ribavirin and a reduction in mortality in studies with critical risk of bias (4 NRS; RR 0.57, 95% CI 0.38 to 0.85;
ribavirin 50773 participants; I2 statistic = 0%).Additional summary of findingsEarly versus late supportive care plus ribavirin for Crimean Congo haemorrhagic feverPatient or population: people diagnosed with suspected or confirmed
ribavirin 50975 or confirmed Crimean Congo haemorrhagic feverSetting: globalIntervention: early supportive care plus ribavirin 1Comparison: late supportive care plus ribavirinOutcomesAnticipated absolute effects* (95% CI)Relative
ribavirin 51023 feverSetting: globalIntervention: early supportive care plus ribavirin1Comparison: late supportive care plus ribavirin OutcomesAnticipated absolute effects* (95% CI)Relative effect (95% CI)Number of participants (studies)Certainty
ribavirin 51190 effect (95% CI)Number of participants (studies)Certainty of the evidence (GRADE)CommentsRisk with Late ribavirin Risk with Early ribavirinMortality in early versus late supportive care plus ribavirin400 per 1000156
ribavirin 51215 participants (studies)Certainty of the evidence (GRADE)CommentsRisk with Late ribavirinRisk with Early ribavirin Mortality in early versus late supportive care plus ribavirin400 per 1000156 per 1000(64 to 380)RR 0.39(0.16
ribavirin 51276 (GRADE)CommentsRisk with Late ribavirinRisk with Early ribavirinMortality in early versus late supportive care plus ribavirin 400 per 1000156 per 1000(64 to 380)RR 0.39(0.16 to 0.95)63(1 non-randomised study)⊕⊖⊖⊖VERY LOW2,3-*The
ribavirin 53072 descriptive analysis. None of these studies attempted to control for confounding.We do not know if ribavirin reduces mortality (very low-certainty evidence).We do not know if ribavirin is more effective when given
ribavirin 53148 confounding.We do not know if ribavirin reduces mortality (very low-certainty evidence).We do not know if ribavirin is more effective when given early with supportive care rather than late with supportive care (very
ribavirin 53305 supportive care rather than late with supportive care (very low-certainty evidence), and we do not know if ribavirin reduces the length of stay in hospital (very low-certainty evidence).In terms of possible adverse effects,
ribavirin 53599 transfusions (very low-certainty evidence), and we do not know what the adverse effects of treating CCHF with ribavirin are, because there is a lack of data for this outcome.In the subsidiary descriptive analysis of studies
ribavirin 53805 studies with a critical risk of bias, the point estimates show an effect skewed towards benefit for ribavirin , as well as increasing heterogeneity.Overall completeness and applicability of evidenceThis review includes
ribavirin 54144 where CCHF is also endemic.There is insufficient reliable evidence to be confident of the effects of ribavirin on mortality, length of hospital stay or the need for transfusion of blood products. There is insufficient
ribavirin 54379 evidence to draw conclusions about the likelihood of serious adverse events occurring when administering ribavirin to people infected with CCHF. Ribavirin is frequently used in the treatment of hepatitis C and the side-effect
ribavirin 54623 established ([117]). However, given different dosing schedules and the differences in the length of use of ribavirin , we do not think this evidence is sufficiently generalizable to CCHF.We wondered whether the non-randomized
ribavirin 54791 generalizable to CCHF.We wondered whether the non-randomized studies would be sufficient to show a benefit for ribavirin if indeed they had a very large effect on mortality and were of sufficient quality. However, all but
ribavirin 55712 and small sample sizes. Because of this, we are unable to reach any conclusions on the efficacy of ribavirin for treating CCHF.For mortality, the single RCT, which was the study with the most reliable internal
ribavirin 56096 downgraded it to very low-certainty evidence for the outcome of mortality.For mortality in early versus late ribavirin , all studies were of a non-randomized design at serious risk of bias. The pooled effect estimate included
ribavirin 59097 previous systematic reviews on this topic ([145]; [114]). We cannot draw conclusions about the efficacy of ribavirin for treating Crimean Congo haemorrhagic fever using the data currently available. This is largely attributable
ribavirin 59464 data is very uncertain.Research in outbreaksIn a broader sense, the current status of the evidence for ribavirin in CCHF highlights the difficulties when non-randomized studies or consensus is used to establish a
ribavirin 61805 situations.Authors' conclusionsImplications for practiceWe do not know from the current literature if ribavirin is an effective treatment for CCHF. Most research on this question is of a non-randomized design and
ribavirin 62458 methodological aspects important in assessing the findings of non randomised studies looking at the effects of ribavirin in CCHF.There remains considerable controversy on the effects of ribavirin in CCHF and whether to use
ribavirin 62533 looking at the effects of ribavirin in CCHF.There remains considerable controversy on the effects of ribavirin in CCHF and whether to use it, reflecting true uncertainty in the field, with some strong advocates
ribavirin 62945 evidence point us in the direction of a randomised clinical trial to establish or disprove the efficacy of ribavirin , as has been suggested previously ([145]; [114])
Select Disease Character Offset Disease Term Instance
Lassa fever 13277 with interferon to treat people who have hepatitis C, and is used alone in treating people who have Lassa fever ([120]). Ribavirin is also used in healthcare settings as a form of post-exposure prophylaxis for those
hepatitis C 13218 these are not currently widely used.Ribavirin is commonly used with interferon to treat people who have hepatitis C , and is used alone in treating people who have Lassa fever ([120]). Ribavirin is also used in healthcare
hepatitis C 54468 administering ribavirin to people infected with CCHF. Ribavirin is frequently used in the treatment of hepatitis C and the side-effect profile is well established ([117]). However, given different dosing schedules and
infectious disease 59982 research therapeutics in outbreak situations. In 2016 WHO issued guidance on managing ethical issues in infectious disease outbreaks which highlights the need to learn as much as possible as quickly as possible and that in
infectious disease 61421 valuable time and resources.As this review demonstrates, establishing efficacy of a therapeutic in acute infectious disease s using observational or non-randomised data is difficult and results can be unreliable. As such the

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