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Clinical Infectious Diseases : An... Oct 2022Bacillus anthracis is a high-priority threat agent because of its widespread availability, easy dissemination, and ability to cause substantial morbidity and mortality....
BACKGROUND
Bacillus anthracis is a high-priority threat agent because of its widespread availability, easy dissemination, and ability to cause substantial morbidity and mortality. Although timely and appropriate antimicrobial therapy can reduce morbidity and mortality, the role of adjunctive therapies continues to be explored.
METHODS
We searched 11 databases for articles that report use of anthrax antitoxins in treatment or prevention of systemic anthrax disease published through July 2019. We identified other data sources through reference search and communication with experts. We included English-language studies on antitoxin products with approval by the US Food and Drug Administration (FDA) for anthrax in humans, nonhuman primates, and rabbits. Two researchers independently reviewed studies for inclusion and abstracted relevant data.
RESULTS
We abstracted data from 12 publications and 2 case reports. All 3 FDA-approved anthrax antitoxins demonstrated significant improvement in survival as monotherapy over placebo in rabbits and nonhuman primates. No study found significant improvement in survival with combination antitoxin and antimicrobial therapy compared to antimicrobial monotherapy. Case reports and case series described 25 patients with systemic anthrax disease treated with antitoxins; 17 survived. Animal studies that used antitoxin monotherapy as postexposure prophylaxis (PEP) demonstrated significant improvement in survival over placebo, with greatest improvements coming with early administration.
CONCLUSIONS
Limited human and animal evidence indicates that adjunctive antitoxin treatment may improve survival from systemic anthrax infection. Antitoxins may also provide an alternative therapy to antimicrobials for treatment or PEP during an intentional anthrax incident that could involve a multidrug-resistant B. anthracis strain.
Topics: Animals; Anthrax; Anti-Bacterial Agents; Anti-Infective Agents; Antitoxins; Bacillus anthracis; Humans; Primates; Rabbits
PubMed: 36251559
DOI: 10.1093/cid/ciac532 -
Toxins Apr 2023Envenomation caused by venomous animals may trigger significant local complications such as pain, edema, localized hemorrhage, and tissue necrosis, in addition to... (Review)
Review
Envenomation caused by venomous animals may trigger significant local complications such as pain, edema, localized hemorrhage, and tissue necrosis, in addition to complications such as dermonecrosis, myonecrosis, and even amputations. This systematic review aims to evaluate scientific evidence on therapies used to target local effects caused by envenomation. The PubMed, MEDLINE, and LILACS databases were used to perform a literature search on the topic. The review was based on studies that cited procedures performed on local injuries following envenomation with the aim of being an adjuvant therapeutic strategy. The literature regarding local treatments used following envenomation reports the use of several alternative methods and/or therapies. The venomous animals found in the search were snakes (82.05%), insects (2.56%), spiders (2.56%), scorpions (2.56%), and others (jellyfish, centipede, sea urchin-10.26%). In regard to the treatments, the use of tourniquets, corticosteroids, antihistamines, and cryotherapy is questionable, as well as the use of plants and oils. Low-intensity lasers stand out as a possible therapeutic tool for these injuries. Local complications can progress to serious conditions and may result in physical disabilities and sequelae. This study compiled information on adjuvant therapeutic measures and underscores the importance of more robust scientific evidence for recommendations that act on local effects together with the antivenom.
Topics: Animals; Antivenins; Snakes; Scorpions; Insecta; Spiders; Snake Bites
PubMed: 37235348
DOI: 10.3390/toxins15050313 -
Expert Opinion on Biological Therapy Sep 2021This systematic review and meta-analysis were performed to explore the association between rabbit thymoglobulin (rATG) doses and transplant-related efficacy and safety... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review and meta-analysis were performed to explore the association between rabbit thymoglobulin (rATG) doses and transplant-related efficacy and safety outcomes.
METHODS
We searched PubMed and Scopus databases from inception up to June 2020. The primary efficacy and safety endpoints in kidney transplant recipients were evaluated.
RESULTS
Data of 23 cohort studies (3457 patients) and three RCTs (154 patients) were extracted and analyzed. rATG doses of ≤4.5 m/kg was associated with lower rates of biopsy proven acute rejection, cytomegalovirus infection, BK virus infection, and malignancy with a comparable rate of delayed graft function, patients' mortality, and death-censored graft loss compared to rATG total doses of 4.5-6 mg/kg or more than 6 mg/kg. The rATG doses of 3-4.5 mg/kg was associated with better outcomes in dose-response analysis.
EXPERT OPINION
Cumulative rATG induction doses as much as 3-4.5 mg/kg is as effective as higher doses regarding to allograft and patient outcomes while minimizing potential adverse effects in kidney transplant recipients.
Topics: Antilymphocyte Serum; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney; Kidney Transplantation; Retrospective Studies
PubMed: 34304664
DOI: 10.1080/14712598.2021.1960978 -
Frontiers in Immunology 2021The global pandemic of the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), places a heavy burden on global...
The global pandemic of the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), places a heavy burden on global public health. Four SARS-CoV-2 variants of concern including B.1.1.7, B.1.351, B.1.617.2, and P.1, and two variants of interest including C.37 and B.1.621 have been reported to have potential immune escape, and one or more mutations endow them with worrisome epidemiologic, immunologic, or pathogenic characteristics. This review introduces the latest research progress on SARS-CoV-2 variants of interest and concern, key mutation sites, and their effects on virus infectivity, mortality, and immune escape. Moreover, we compared the effects of various clinical SARS-CoV-2 vaccines and convalescent sera on epidemic variants, and evaluated the neutralizing capability of several antibodies on epidemic variants. In the end, SARS-CoV-2 evolution strategies in different transmission stages, the impact of different vaccination strategies on SARS-CoV-2 immune escape, antibody therapy strategies and COVID-19 epidemic control prospects are discussed. This review will provide a systematic and comprehensive understanding of the secret of SARS-CoV-2 variants of interest/concern and immune escape.
Topics: Animals; Antibodies, Monoclonal; Antibodies, Neutralizing; Antibodies, Viral; COVID-19; COVID-19 Vaccines; Humans; Immune Evasion; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34804024
DOI: 10.3389/fimmu.2021.744242 -
Archives of Toxicology Feb 2024Snakebite in India is a severe problem as it causes a mortality rate of 58,000 and a disability rate of 140,000 every year which is the highest among any other country.... (Meta-Analysis)
Meta-Analysis Review
Snakebite in India is a severe problem as it causes a mortality rate of 58,000 and a disability rate of 140,000 every year which is the highest among any other country. Antivenom is the primary therapy for snakebite, and its manufacturing techniques have essentially stayed unaltered for over a century. Indian polyvalent antivenom, a scientifically validated medicine for treating the toxic effects of snakebites, is available against the venom of the so-called Big Four snakes namely Spectacled cobra (Naja naja), Saw-scaled viper (Echis carinatus), Russell's viper (Daboia russelli) and the Common krait (Bungarus caeruleus), responsible for majority of the deaths in India. India hosts many other species of snakes, including cobras, kraits, saw-scaled vipers, sea snakes, and pit vipers, responsible for clinically severe envenomation. Neutralization strategy has been applied to access the efficacy of antivenoms, crucial for reducing snake bite deaths and disabilities. This review aims to conduct a systematic review and meta-analysis on the neutralization efficiency of the Polyvalent Antivenom (PAV) and focus on the factors that may contribute to the poor recognition of the antivenom towards the venom toxins. Reports focusing on the investigation of antivenom efficacy were searched and collected from several databases. Preclinical studies that reported the neutralization efficacy of the commercial antivenom against the medically important snakes of India were included. The articles were screened based on the inclusion criteria and 8 studies were shortlisted for meta-analysis. Pooled proportion was calculated for the antivenom efficacy reported by the studies and was found to be statistically significant with a 95% confidence interval. The heterogenicity in the venom toxicity and neutralization potency of the antivenom was evident in the overall estimate (proportion) and individual data. We provide comprehensive evidence on antivenom efficacy against medically important snakes from various parts of India which may aid in identifying the gaps in snake envenomation therapy and the need for novel potentially improved treatment of snakebites.
Topics: Animals; Antivenins; Snake Bites; Clinical Relevance; Daboia; Echis; Venomous Snakes; Bungarus
PubMed: 38153416
DOI: 10.1007/s00204-023-03643-9 -
PloS One 2023Rabbit anti-thymocyte globulin (ATG) has been used in allogeneic hematopoietic stem cell transplantation (Allo-HSCT) for graft-versus-host disease (GvHD) prophylaxis.... (Meta-Analysis)
Meta-Analysis
Rabbit anti-thymocyte globulin (ATG) has been used in allogeneic hematopoietic stem cell transplantation (Allo-HSCT) for graft-versus-host disease (GvHD) prophylaxis. Since the best dose has not been defined yet, this study aimed to determine the efficacy and safety of different doses of ATG in Allo-HSCT. Data sources were MEDLINE/PUBMED, EMBASE, Cochrane Library, Web of Science, LILACS, and SciELO. Studies were eligible when comparing doses of ATG. The higher dose was in the intervention group. A total of 22 articles (2002-2022) were included. Higher doses (4-12 mg/kg) of ATG-T reduced the incidence of grade III-IV acute GvHD (RR 0.60; 95%CI 0.42-0.84) and limited chronic GvHD (RR 0.64 95%CI 0.45-0.92) compared with lower doses (2-7.5 mg/kg). Higher doses increased the Epstein-Barr virus (RR 1.90 95% CI 1.49-2.42) and Cytomegalovirus reactivation (RR, 1.30; 95% CI 1.03-1.64). Relapse rates were higher in the higher dose group (RR 1.34, 95% CI 1.07-167). The ATG-T dose ≥7mg/kg versus the lower dose showed a number needed to treat 7.4 for acute GvHD III-IV, with a number to harm of 7.7 for relapse at one year in the higher dose group. A dose lower than 7 mg/kg suggests a better risk-benefit ratio than a higher one. Well-designed RCT is needed to define the best risk-benefit doses. Trial registration: Trial registration number: PROSPERO: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020173449.
Topics: Humans; Antilymphocyte Serum; Epstein-Barr Virus Infections; Transplantation, Homologous; Herpesvirus 4, Human; Hematopoietic Stem Cell Transplantation; Recurrence; Graft vs Host Disease; Chronic Disease; Retrospective Studies
PubMed: 37071663
DOI: 10.1371/journal.pone.0284476 -
Reviews in Medical Virology Mar 2022BNT162b2 and mRNA-1273 are two types of mRNA-based vaccine platforms that have received emergency use authorization. The emergence of novel severe acute respiratory... (Review)
Review
Potency of BNT162b2 and mRNA-1273 vaccine-induced neutralizing antibodies against severe acute respiratory syndrome-CoV-2 variants of concern: A systematic review of in vitro studies.
BNT162b2 and mRNA-1273 are two types of mRNA-based vaccine platforms that have received emergency use authorization. The emergence of novel severe acute respiratory syndrome (SARS-CoV-2) variants has raised concerns of reduced sensitivity to neutralization by their elicited antibodies. We aimed to systematically review the most recent in vitro studies evaluating the effectiveness of BNT162b2 and mRNA-1273 induced neutralizing antibodies against SARS-CoV-2 variants of concern. We searched PubMed, Scopus, and Web of Science in addition to bioRxiv and medRxiv with terms including 'SARS-CoV-2', 'BNT162b2', 'mRNA-1273', and 'neutralizing antibody' up to June 29, 2021. A modified version of the Consolidated Standards of Reporting Trials (CONSORT) checklist was used for assessing included study quality. A total 36 in vitro studies meeting the eligibility criteria were included in this systematic review. B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta) are four SARS-CoV-2 variants that have recently been identified as variants of concern. Included studies implemented different methods regarding pseudovirus or live virus neutralization assays for measuring neutralization titres against utilized viruses. After two dose vaccination by BNT162b2 or mRNA-1273, the B.1.351 variant had the least sensitivity to neutralizing antibodies, while B.1.1.7 variant had the most sensitivity; that is, it was better neutralized relative to the comparator strain. P.1 and B.1.617.2 variants had an intermediate level of impaired naturalization activity of antibodies elicited by prior vaccination. Our review suggests that immune sera derived from vaccinated individuals might show reduced protection of individuals immunized with mRNA vaccines against more recent SARS-CoV-2 variants of concern.
Topics: 2019-nCoV Vaccine mRNA-1273; Antibodies, Neutralizing; Antibodies, Viral; BNT162 Vaccine; COVID-19; COVID-19 Vaccines; Humans; SARS-CoV-2
PubMed: 34286893
DOI: 10.1002/rmv.2277 -
Transplantation and Cellular Therapy Aug 2021With the increasing number of non-matched donor hematopoietic stem cell transplantations (HSCTs) has come increasing evidence regarding factors affecting graft outcomes.... (Meta-Analysis)
Meta-Analysis
With the increasing number of non-matched donor hematopoietic stem cell transplantations (HSCTs) has come increasing evidence regarding factors affecting graft outcomes. One factor affecting graft outcomes currently being evaluated is anti-HLA donor-specific antibodies (DSAs). In this, we analyzed the clinical relevance of anti-HLA DSAs in patients who have undergone HSCT at a population level by conducting a systematic review of existing literature. A comprehensive search was conducted through PubMed, Embase, the Cochrane library, and Web of Science from inception to January 1, 2021. A meta-analysis was performed of the association between anti-HLA DSAs and primary graft failure (PGF) with further subgroup analyses. The search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 920 eligible citations were identified, out of which 15 studies were included in the final meta-analyses after application of rigorous selection criteria and independent review. A total of 2436 patients were included in these 15 studies. Patients with anti-HLA DSAs prior to undergoing HSCT had a 7.47-fold increased risk of PGF failure compared with patients without anti-HLA DSAs (odds ratio, 7.47; 95% confidence interval, 4.54 to 12.28, P < .001; I= 28.91%, P = .1315). In subgroup and meta-regression analyses, area, Newcastle Ottawa Scale score, mean fluorescence intensity cutoff, primary disease, HSCT type, graft source, and pretransplantation desensitization did not affect the impact of anti-HLA DSAs on PGF. There also was no significant difference in impact between HLA class I and II on PGF. We conclude that the prior presence of anti-HLA DSAs has a negative impact on graft outcomes in recipients of haploidentical and umbilical cord blood HSCT.
Topics: Antibodies; Antilymphocyte Serum; HLA Antigens; Hematopoietic Stem Cell Transplantation; Humans; Tissue Donors
PubMed: 33989833
DOI: 10.1016/j.jtct.2021.04.030 -
Toxicon : Official Journal of the... Mar 2023The World Health Organization has listed Snakebite Envenoming (SBE) as a priority neglected tropical disease, with a worldwide annual snakebite affecting 5.4 million... (Meta-Analysis)
Meta-Analysis
The World Health Organization has listed Snakebite Envenoming (SBE) as a priority neglected tropical disease, with a worldwide annual snakebite affecting 5.4 million people and injuring 2.7 million lives. In many parts of rural areas of Africa and Asia, medicinal plants have been used as alternatives to conventional antisnake venom (ASV) due in part to inaccessibility to hospitals. Systemic reviews (SR) of laboratory-based preclinical studies play an essential role in drug discovery. We conducted an SR to evaluate the relationship between interventional medicinal plants and their observed effects on venom-induced experiments. This SR was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The Modified collaborative approach to meta-analysis and review of animal data from experimental studies (CAMARADES) and SYRCLE's risk of bias tools were used to appraise the included studies. Data were searched online in Medline via PubMed, Embase via OVID, and Scopus. Studies reporting in vivo and in vitro pharmacological activities of African medicinal plants/extracts/constituents against venom-induced pathologies were identified and included for screening. Data from the included studies were extracted and synthesized. Ten studies reported statistically significant percentage protection (40-100%) of animals against venom-induced lethality compared with control groups that received no medicinal plant intervention. Sixteen studies reported significant effects (p ≤ 0.05) against venom-induced pathologies compared with the control group; these include hemolytic, histopathologic, necrotic, and anti-enzymatic effects. The plant family Fabaceae has the highest number of studies reporting its efficacy, followed by Annonaceae, Malvaceae, Combretaceae, Sterculiaceae, and Olacaceae. Some African medicinal plants are preclinically effective against venom-induced lethality, hematotoxicity, and cytotoxicity. The evidence was extracted from three in vitro studies, nine in vivo studies, and five studies that combined both in vivo and in vitro models. The effective plants belong to the Fabaceae family, followed by Malvaceae, and Annonaceae.
Topics: Animals; Africa; Antivenins; Asia; Plants, Medicinal; Snake Bites; Treatment Outcome
PubMed: 36706926
DOI: 10.1016/j.toxicon.2023.107035 -
Annals of Hematology Feb 2021Graft-versus-host disease (GVHD) prophylaxis based on post-transplant cyclophosphamide (PTCy) or antithymocyte globulin (ATG) is widely used in allogeneic hematopoietic... (Comparative Study)
Comparative Study Meta-Analysis
Graft-versus-host disease (GVHD) prophylaxis based on post-transplant cyclophosphamide (PTCy) or antithymocyte globulin (ATG) is widely used in allogeneic hematopoietic stem cell transplantations (allo-HCT). The differential impacts of PTCy and ATG on transplantation outcomes are not well characterized. Here we report a meta-analysis of PTCy versus ATG in allo-HCT. Ten studies were eligible, and a total of 1871 patients were included. The incidence of II-IV aGVHD, III-IV aGVHD, and NRM were significantly lower in PTCy arm (HR = 0.63, 95% CI 0.45-0.89; HR = 0.35, 95% CI 0.16-0.77; HR = 0.59, 95% CI 0.48-0.73). PTCy was associated with a better OS and PFS (HR = 0.62, 95% CI = 0.53-0.73; HR = 0.76, 95% CI 0.62-0.93). The relapse rate and cGVHD incidence were not significantly different between PTCy and ATG (HR = 0.85, 95% CI 0.68-1.07; HR = 0.65, 95% CI 0.38-1.12). Thus, compared with ATG, PTCy has a better aGVHD control and OS benefit, without increasing relapse risk, which needs further validation in prospective randomized trials.
Topics: Allografts; Antilymphocyte Serum; Cyclophosphamide; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Recurrence; Risk Factors
PubMed: 33420575
DOI: 10.1007/s00277-021-04399-x