Abstract

Human babesiosis is a parasitic disease prevalent in the Northeastern and Midwestern United States (US). Treatment with antibiotics is the standard of care but red cell exchange (RCE) has been used as an adjunctive treatment in more severe disease. Data for the efficacy of RCE in the treatment of babesiosis has been based on case reports and case series. An English language literature search was conducted for cases of babesiosis treated with RCE since 1980 and relevant laboratory and clinical outcome data were extracted. Similar data were obtained on severe cases of babesiosis referred for RCE in our hospitals in the time period 2000 to 2020. Fifty reports including forty-one individual case reports and nine case series were retrieved. There were 108 patients that underwent RCE with an overall mortality rate of 20%. Some patients had more than one RCE. The patients varied in the level of anemia and evidence of compromise of renal or pulmonary function. The pre-RCE level of parasitemia varied between 1.7% to 85% with the vast majority >10%. The post-RCE level of parasitemia varied between 1% to 10%. Since 2000, 32 patients were referred for RCE in our hospitals and RCE was performed on 23 of 32. There were more patients treated with RCE in the second decade as compared to the first decade, 19 versus 4 respectively. The overall mortality was 22% similar to the national data. Comparing the cohort treated with RCE to the 9 patients who were treated only with antibiotics, there were similar levels of parasitemia and laboratory parameters. The overall number of days needed to achieve a parasite count <1% was similar between the two cohorts and mortality for the antibiotics only cohort was 0%. More than 40 years after the first reported case of RCE in severe babesiosis it cannot be concluded that this adjunctive therapy favorably influences the clinical outcome. Since there is largely equipoise, a registry of severe patients treated with or without RCE could identify a benefit or otherwise.

Abstract

BACKGROUND Convalescent plasma administration may be of clinical benefit in patients with severe influenza, but reports on the efficacy of this therapy vary. METHODS We conducted a systematic review and meta-analysis assessing randomized controlled trials (RCTs) involving the administration of convalescent plasma to treat severe influenza. Healthcare databases were searched in February 2020. All records were screened against eligibility criteria, and the risks of bias were assessed. The primary outcome was the fatality rate. RESULTS A total of 2861 studies were retrieved and screened. Five eligible RCTs were identified. Pooled analyses yielded no evidence that using convalescent plasma to treat severe influenza resulted in significant reductions in mortality (odds ratio, 1.06; 95% CI, 0.51-2·23; P = 0.87; I(2) = 35%), number of days in the intensive care unit, or number of days on mechanical ventilation. This treatment may have the possible benefits of increasing hemagglutination inhibition titers and reducing influenza B viral loads and cytokine levels. No serious adverse events were reported. The included studies were generally of high quality with a low risk of bias. CONCLUSIONS The administration of convalescent plasma appears safe but may not reduce the mortality, number of days in the intensive care unit, or number of days on mechanical ventilation in patients with severe influenza.

Abstract

BACKGROUND Convalescent plasma and hyperimmune immunoglobulin may reduce mortality in patients with viral respiratory diseases, and are currently being investigated in trials as potential therapy for coronavirus disease 2019 (COVID-19). A thorough understanding of the current body of evidence regarding the benefits and risks is required.  OBJECTIVES To continually assess, as more evidence becomes available, whether convalescent plasma or hyperimmune immunoglobulin transfusion is effective and safe in treatment of people with COVID-19. SEARCH METHODS We searched the World Health Organization (WHO) COVID-19 Global Research Database, MEDLINE, Embase, Cochrane COVID-19 Study Register, Centers for Disease Control and Prevention COVID-19 Research Article Database and trial registries to identify completed and ongoing studies on 19 August 2020. SELECTION CRITERIA We followed standard Cochrane methodology. We included studies evaluating convalescent plasma or hyperimmune immunoglobulin for people with COVID-19, irrespective of study design, disease severity, age, gender or ethnicity. We excluded studies including populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)) and studies evaluating standard immunoglobulin. DATA COLLECTION AND ANALYSIS We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane 'Risk of bias' 2.0 tool for randomised controlled trials (RCTs), the Risk of Bias in Non-randomised Studies - of Interventions (ROBINS-I) tool for controlled non-randomised studies of interventions (NRSIs), and the assessment criteria for observational studies, provided by Cochrane Childhood Cancer for non-controlled NRSIs. We rated the certainty of evidence using the GRADE approach for the following outcomes: all-cause mortality at hospital discharge, mortality (time to event), improvement of clinical symptoms (7, 15, and 30 days after transfusion), grade 3 and 4 adverse events (AEs), and serious adverse events (SAEs). MAIN RESULTS This is the second living update of our review. We included 19 studies (2 RCTs, 8 controlled NRSIs, 9 non-controlled NRSIs) with 38,160 participants, of whom 36,081 received convalescent plasma. Two completed RCTs are awaiting assessment (published after 19 August 2020). We identified a further 138 ongoing studies evaluating convalescent plasma or hyperimmune immunoglobulin, of which 73 are randomised (3 reported in a study registry as already being completed, but without results). We did not identify any completed studies evaluating hyperimmune immunoglobulin. We did not include data from controlled NRSIs in data synthesis because of critical risk of bias. The overall certainty of evidence was low to very low, due to study limitations and results including both potential benefits and harms.  Effectiveness of convalescent plasma for people with COVID-19  We included results from two RCTs (both stopped early) with 189 participants, of whom 95 received convalescent plasma. Control groups received standard care at time of treatment without convalescent plasma. We are uncertain whether convalescent plasma decreases all-cause mortality at hospital discharge (risk ratio (RR) 0.55, 95% confidence interval (CI) 0.22 to 1.34; 1 RCT, 86 participants; low-certainty evidence).  We are uncertain whether convalescent plasma decreases mortality (time to event) (hazard ratio (HR) 0.64, 95% CI 0.33 to 1.25; 2 RCTs, 189 participants; low-certainty evidence). Convalescent plasma may result in little to no difference in improvement of clinical symptoms (i.e. need for respiratory support) at seven days (RR 0.98, 95% CI 0.30 to 3.19; 1 RCT, 103 participants; low-certainty evidence). Convalescent plasma may increase improvement of clinical symptoms at up to 15 days (RR 1.34, 95% CI 0.85 to 2.11; 2 RCTs, 189 participants; low-certainty evidence), and at up to 30 days (RR 1.13, 95% CI 0.88 to 1.43; 2 studies, 188 participants; low-certainty evidence).  No studies repo ted on quality of life.  Safety of convalescent plasma for people with COVID-19 We included results from two RCTs, eight controlled NRSIs and nine non-controlled NRSIs assessing safety of convalescent plasma. Reporting of safety data and duration of follow-up was variable. The controlled studies reported on AEs and SAEs only in participants receiving convalescent plasma. Some, but not all, studies included death as a SAE.  The studies did not report the grade of AEs. Fourteen studies (566 participants) reported on AEs of possible grade 3 or 4 severity. The majority of these AEs were allergic or respiratory events. We are very uncertain whether convalescent plasma therapy affects the risk of moderate to severe AEs (very low-certainty evidence).  17 studies (35,944 participants) assessed SAEs for 20,622 of its participants. The majority of participants were from one non-controlled NRSI (20,000 participants), which reported on SAEs within the first four hours and within an additional seven days after transfusion. There were 63 deaths, 12 were possibly and one was probably related to transfusion. There were 146 SAEs within four hours and 1136 SAEs within seven days post-transfusion. These were predominantly allergic or respiratory, thrombotic or thromboembolic and cardiac events. We are uncertain whether convalescent plasma therapy results in a clinically relevant increased risk of SAEs (low-certainty evidence). AUTHORS' CONCLUSIONS We are uncertain whether convalescent plasma is beneficial for people admitted to hospital with COVID-19. There was limited information regarding grade 3 and 4 AEs to determine the effect of convalescent plasma therapy on clinically relevant SAEs. In the absence of a control group, we are unable to assess the relative safety of convalescent plasma therapy.  While major efforts to conduct research on COVID-19 are being made, recruiting the anticipated number of participants into these studies is problematic. The early termination of the first two RCTs investigating convalescent plasma, and the lack of data from 20 studies that have completed or were due to complete at the time of this update illustrate these challenges. Well-designed studies should be prioritised. Moreover, studies should report outcomes in the same way, and should consider the importance of maintaining comparability in terms of co-interventions administered in all study arms.  There are 138 ongoing studies evaluating convalescent plasma and hyperimmune immunoglobulin, of which 73 are RCTs (three already completed). This is the second living update of the review, and we will continue to update this review periodically. Future updates may show different results to those reported here.

Abstract

The global incidence of dengue has increased sevenfold between 1990 and 2013. Despite a low case fatality rate (<1%), during epidemics, due to the large number of people affected, overall mortality rates can be significant. The risk of clinically significant bleeding in dengue is unpredictable and often contributes to an adverse outcome. This systematic review focuses on the evidence for prophylactic and therapeutic interventions for bleeding in dengue infection. PubMed, CINAHL, Cochrane Library, Embase and Google Scholar were searched for randomized, quasi-randomized and non-randomized, prospective or retrospective studies that had a control group alongside an intervention aimed at stopping or preventing bleeding in dengue infection. Eleven studies that included 1904 patients in 12 study arms were eligible. These assessed the role of platelet transfusion [two randomized controlled trials (RCTs) and three non-randomized studies], plasma transfusion (one RCT), recombinant activated factor VII (one RCT), anti-D globulin (two RCTs), immunoglobulin (one RCT) and interleukin 11 (one RCT) as prevention or treatment for bleeding. Due to significant heterogeneity in study design and outcome reporting, a meta-analysis was not performed. Currently there is no evidence that any of the above interventions would have a beneficial effect in preventing or treating clinically significant bleeding in dengue.

Abstract

BACKGROUND Administration of convalescent plasma, serum, or hyperimmune immunoglobulin may be of clinical benefit for treatment of severe acute respiratory infections (SARIs) of viral etiology. We conducted a systematic review and exploratory meta-analysis to assess the overall evidence. METHODS Healthcare databases and sources of grey literature were searched in July 2013. All records were screened against the protocol eligibility criteria, using a 3-stage process. Data extraction and risk of bias assessments were undertaken. RESULTS We identified 32 studies of SARS coronavirus infection and severe influenza. Narrative analyses revealed consistent evidence for a reduction in mortality, especially when convalescent plasma is administered early after symptom onset. Exploratory post hoc meta-analysis showed a statistically significant reduction in the pooled odds of mortality following treatment, compared with placebo or no therapy (odds ratio, 0.25; 95% confidence interval, .14-.45; I(2) = 0%). Studies were commonly of low or very low quality, lacked control groups, and at moderate or high risk of bias. Sources of clinical and methodological heterogeneity were identified. CONCLUSIONS Convalescent plasma may reduce mortality and appears safe. This therapy should be studied within the context of a well-designed clinical trial or other formal evaluation, including for treatment of Middle East respiratory syndrome coronavirus CoV infection. The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Abstract

INTRODUCTION Dengue haemorrhagic fever and dengue shock syndrome are major causes of hospital admission and mortality in children. METHODS AND OUTCOMES We conducted a systematic review and aimed to answer the following clinical question: What are the effects of supportive treatments for dengue haemorrhagic fever or dengue shock syndrome in children? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2014 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS We found nine studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS In this systematic review we present information relating to the effectiveness and safety of the following interventions: adding blood component transfusion to standard intravenous fluids; adding corticosteroids or intravenous immunoglobulin to standard intravenous fluids; and crystalloids versus colloids.

Abstract

BACKGROUND Blood transfusion is used in patients with severe malarial anaemia, but risks adverse reactions, transmission of disease, and is complicated to organise in developing countries. OBJECTIVES This review evaluates the effects of routine blood transfusion for severe anaemia on death and adverse outcomes in malarious areas. SEARCH STRATEGY We searched the Cochrane Infectious Diseases Group Specialized Register (July 2006), CENTRAL (The Cochrane Library Issue 3, 2006), MEDLINE (1966 to July 2006), EMBASE (1980 to July 2006), LILACS (July 2006), and reference lists of relevant articles. We contacted researchers and organizations working in the field. SELECTION CRITERIA Randomised and quasi-randomised trials of blood transfusion compared with conservative management in malaria-associated severe anaemia. DATA COLLECTION AND ANALYSIS Trials were identified and data extracted by a single reviewer (MM) and checked by a second (HS). Inclusion criteria were applied and data were extracted independently by both reviewers. MAIN RESULTS Two randomised trials of 230 children were included. In the transfusion group, there was a non-signficant tendency towards fewer deaths (RR 0.41, 95% CI 0.06 to 2.70), but a trend towards more severe adverse events (RR 8.60, 95% CI 1.11 to 66.43). In one trial by Bojang (1997a) respiratory distress was less common and hospital stay was shorter in the transfusion group (WMD 1.88 days, 95% CI 2.41 to 1.35). Subsequent need for urgent blood transfusion was less common in the transfusion group (RR 0.12, 95% CI 0.02 to 0.68). Day 28 packed cell volume was less in the transfusion group (WMD -1.34, 95% CI -2.57 to -0.11). There was no information on HIV or Hepatitis B virus transmission. AUTHORS' CONCLUSIONS There is insufficient data to be sure whether routinely giving blood to clinically stable children with severe anaemia in endemic malarious areas reduces death, or results in higher haematocrit measured at one month.