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Clinical Infectious Diseases : An... Oct 2022Anthrax is a toxin-mediated zoonotic disease caused by Bacillus anthracis, with a worldwide distribution recognized for millennia. Bacillus anthracis is considered a...
BACKGROUND
Anthrax is a toxin-mediated zoonotic disease caused by Bacillus anthracis, with a worldwide distribution recognized for millennia. Bacillus anthracis is considered a potential biowarfare agent.
METHODS
We completed a systematic review for clinical and demographic characteristics of adults and children hospitalized with anthrax (cutaneous, inhalation, ingestion, injection [from contaminated heroin], primary meningitis) abstracted from published case reports, case series, and line lists in English from 1880 through 2018, assessing treatment impact by type and severity of disease. We analyzed geographic distribution, route of infection, exposure to anthrax, and incubation period.
RESULTS
Data on 764 adults and 167 children were reviewed. Most cases reported for 1880 through 1915 were from Europe; those for 1916 through 1950 were from North America; and from 1951 on, cases were from Asia. Cutaneous was the most common form of anthrax for all populations. Since 1960, adult anthrax mortality has ranged from 31% for cutaneous to 90% for primary meningitis. Median incubation periods ranged from 1 day (interquartile range [IQR], 0-4) for injection to 7 days (IQR, 4-9) for inhalation anthrax. Most patients with inhalation anthrax developed pleural effusions and more than half with ingestion anthrax developed ascites. Treatment and critical care advances have improved survival for those with systemic symptoms, from approximately 30% in those untreated to approximately 70% in those receiving antimicrobials or antiserum/antitoxin.
CONCLUSIONS
This review provides an improved evidence base for both clinical care of individual anthrax patients and public health planning for wide-area aerosol releases of B. anthracis spores.
Topics: Adult; Aerosols; Anthrax; Antitoxins; Bacillus anthracis; Biological Warfare Agents; Child; Heroin; Humans; Respiratory Tract Infections
PubMed: 36251560
DOI: 10.1093/cid/ciac534 -
Pharmaceutical Biology Dec 2022Snake envenomation is one of the neglected health problems in Tanzania. Since most people, especially in rural areas, suffer from its burden, their cases are not...
CONTEXT
Snake envenomation is one of the neglected health problems in Tanzania. Since most people, especially in rural areas, suffer from its burden, their cases are not documented due to reliance on medicinal plants. Despite the pivotal role of medicinal plants in treating snakebites, there is a paucity of information.
OBJECTIVE
This review documents medicinal plants used to treat snakebites in Tanzania.
MATERIALS AND METHODS
A systematic search using electronic databases such as PubMed, Google Scholar, Scopus, Science Direct and grey literature was conducted to retrieve relevant information on medicinal plants used to treat snakebites in Tanzania. The review was conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The obtained information from 19 published articles was organized and analysed based on citation frequency.
RESULTS
A total of 109 plant species belonging to 49 families are used as snakebite antivenom in Tanzania. Fabaceae had the highest number of medicinal plants (19.3%). The dominant plant growth forms were trees (35%) and shrubs (33%). Roots were the most frequently used plant part (54%), followed by leaves (26%) and bark (11%). Pers. (Annonaceae), (L.) (Fabaceae), Baill. (Euphorbiaceae), E.Mey. ex Tul. (Phyllanthaceae), L. (Menispermaceae) and Guill. & Perr. (Fabaceae) were the most cited medicinal plants.
CONCLUSIONS
Tanzania has diverse plants used for snakebite treatment; a few have been analysed for their bioactive components. Further study of the phytochemicals may provide scientific information to develop snakebite drugs.
Topics: Antivenins; Ethnobotany; Medicine, Traditional; Phytotherapy; Plants, Medicinal; Snake Bites; Tanzania
PubMed: 36205572
DOI: 10.1080/13880209.2022.2123942 -
Frontiers in Immunology 2020There is an urgent need to strengthen the implementation of the 3Rs principle (Replacement, Reduction and Refinement) in the use of experimental animals in toxinological...
There is an urgent need to strengthen the implementation of the 3Rs principle (Replacement, Reduction and Refinement) in the use of experimental animals in toxinological research and in the assessment of the neutralizing efficacy of snake antivenoms. This is a challenging task owing to the inherent complexity of snake venoms. The state of the art on this topic is hereby reviewed, with emphasis on the studies in which a correlation has been observed between toxicity tests and surrogate assays, particularly in the study of lethal activity of venoms and its neutralization. Correlations have been described with some venoms-antivenoms when using: (a) enzyme immunoassays, (b) hemagglutination, (c) enzyme assays (proteinase, phospholipase A), (d) coagulant effect on plasma, (e) cell culture assays for cytotoxicity, (f) functional assays for assessing neurotoxicity , (g) use of hens' eggs, and (h) antivenomics. Additionally, the routine introduction of analgesia in these assays and the design of more 'humane' protocols for the lethality test are being pursued. It is expected that the next years will witness a growing awareness of the relevance of the 3Rs principles in antivenom testing, and that new alternatives and more 'humane' experimental designs will emerge in this field.
Topics: Animals; Antivenins; Humans; In Vitro Techniques; Neutralization Tests; Snake Venoms
PubMed: 33505403
DOI: 10.3389/fimmu.2020.617429 -
Haematologica Jan 2020Immunosuppressive therapy (IST) is one therapy option for treatment of patients with lower-risk myelodysplastic syndromes (MDS). However, the use of several different... (Meta-Analysis)
Meta-Analysis
Immunosuppressive therapy (IST) is one therapy option for treatment of patients with lower-risk myelodysplastic syndromes (MDS). However, the use of several different immunosuppressive regimens, the lack of high-quality studies, and the absence of validated predictive biomarkers pose important challenges. We conducted a systematic review and meta-analysis according to the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines and searched MEDLINE PubMed, Ovid EMBASE, COCHRANE registry of clinical trials (CENTRAL), and the Web of Science without language restriction from inception through September 2018, as well as relevant conference proceedings and abstracts, for prospective cohort studies or clinical trials investigating IST in MDS. Fixed and Random-effects models were used to pool response rates. We identified nine prospective cohort studies and 13 clinical trials with a total of 570 patients. Overall response rate was 42.5% [95% confidence interval (CI): 36.1-49.2%] including a complete remission rate of 12.5% (95%CI: 9.3-16.6%) and red blood cell transfusion independence rate of 33.4% (95% CI: 25.1-42.9%). The most commonly used forms of IST were anti-thymocyte globulin alone or in combination with cyclosporin A with a trend towards higher response rates with combination therapy. Progression rate to acute myeloid leukemia was 8.6% per patient year (95%CI: 3.3-13.9%). Overall survival and adverse events were only inconsistently reported. We were unable to validate any biomarkers predictive of a therapeutic response to IST. IST for treatment of lower-risk MDS patients can be successful to alleviate transfusion burden and associated sequelae.
Topics: Antilymphocyte Serum; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Myelodysplastic Syndromes; Prospective Studies
PubMed: 31004015
DOI: 10.3324/haematol.2019.219345 -
Expert Review of Clinical Immunology Aug 2019: Innate immune response and bone remodeling are key factors contributing to the pathogenesis of psoriatic arthritis (PsA). Moreover, the evidence of autoantibodies in...
: Innate immune response and bone remodeling are key factors contributing to the pathogenesis of psoriatic arthritis (PsA). Moreover, the evidence of autoantibodies in patients' sera suggests an autoimmune side in PsA. Besides the immune pathways, studies strongly support the role of genetic risk alleles in affecting the clinical heterogeneity of PsA as well as the response to therapy. A good clinical response to treatment, indeed, represents a challenge in PsA patients and the identification of patient-targeted therapies is still a critical issue. : We performed a systematic review aiming at describing new evidence on PsA pathogenesis and treatments. Reported items for systematic reviews (PRISMA checklist) were analyzed. Studies included from the PubMed database addressed the following items: innate immunity, autoimmunity, bone remodeling, and therapeutic targets in PsA; time frame of research 1970-2019. Specifically, we reviewed data on IL-17 inhibitors, abatacept, JAK inhibitors, ABT 122, and A (3) adenosine receptors agonist, CF101. : In PsA an intriguing pathogenetic network has been documented. Several biological and synthetic drugs are promising in terms of efficacy and safety profile.
Topics: Abatacept; Adenosine; Alleles; Arthritis, Psoriatic; Genetic Predisposition to Disease; HLA Antigens; Humans; Immunoglobulins; Immunosuppressive Agents; Treatment Outcome
PubMed: 31177868
DOI: 10.1080/1744666X.2019.1627876 -
PLoS Neglected Tropical Diseases Aug 2021The 20-minute whole blood clotting test (20WBCT) has been used to detect coagulopathy following snakebite for almost 50 years. A systematic review and meta-analysis of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The 20-minute whole blood clotting test (20WBCT) has been used to detect coagulopathy following snakebite for almost 50 years. A systematic review and meta-analysis of the 20WBCT was conducted to evaluate the accuracy of the 20WBCT to detect coagulopathy, indicative of systemic envenoming.
METHODS AND FINDINGS
Databases were searched from inception up to 09/12/2020 to identify studies that compared the 20WBCT and INR/fibrinogen on five or more subjects. Data was extracted from full-text articles by two reviewers using a predetermined form. Authors of 29 studies that lacked sufficient details in the manuscript were contacted and included if data meeting the inclusion criteria were provided. Included studies were evaluated for bias using a tailored QUADAS-2 checklist. The study protocol was prospectively registered on PROSPERO database (CRD42020168953). The searches identified 3,599 studies, 15 met the inclusion criteria and 12 were included in the meta-analysis. Data was reported from 6 countries and included a total of 2,270 patients. The aggregate weighted sensitivity of the 20WBCT at detecting INR >1.4 was 0.84 (CI 0.61 to 0.94), the specificity was 0.91 (0.76 to 0.97) and the SROC AUC was 0.94 (CI 0.91 to 0.96). The aggregate weighted sensitivity of the 20WBCT at detecting fibrinogen <100 mg/dL was 0.72 (CI 0.58 to 0.83), the specificity was 0.94 (CI 0.88 to 0.98) and the SROC AUC was 0.93 (0.91 to 0.95). Both analyses that used INR and fibrinogen as the reference test displayed considerable heterogeneity.
CONCLUSIONS
In the absence of laboratory clotting assays, the 20WBCT remains a highly specific and fairly sensitive bedside test at detecting coagulopathy following snakebite. However, clinicians should be aware of the importance of operator training, standardized equipment and the lower sensitivity of the 20WBCT at detecting mild coagulopathy and resolution of coagulopathy following antivenom.
Topics: Antivenins; Blood Coagulation; Blood Coagulation Tests; Fibrinogen; Humans; International Normalized Ratio; Sensitivity and Specificity; Snake Bites
PubMed: 34375338
DOI: 10.1371/journal.pntd.0009657 -
PloS One 2023Cross-neutralizing strategy has been applied to improve access to antivenoms, a key to reducing mortality and disability of snakebite envenoming. However, preclinical...
BACKGROUND
Cross-neutralizing strategy has been applied to improve access to antivenoms, a key to reducing mortality and disability of snakebite envenoming. However, preclinical studies have been conducted to identify antivenoms' cross-neutralizing ability when clinical studies may not be considered ethical. Therefore, this study aimed to identify and summarize scattered evidence regarding the preclinical efficacy of antivenoms against Asian snakes.
METHODOLOGY/PRINCIPLE FINDINGS
In this systematic review, we searched for articles published until May 30, 2022, in PubMed, Scopus, Web of Science, and Embase. Preclinical studies that reported the available antivenoms' neutralizing ability against Asian snake lethality were included. Quality assessment was performed using the Systematic Review Centre for Laboratory animal Experimentation's risk of bias tool and the adapted the Animal Research Reporting In Vivo Experiments guidelines. The availability of effective antivenoms against Asian snakes was analyzed by comparing data from included studies with snakebite-information and data platforms developed by the World Health Organization. Fifty-two studies were included. Most studies assessed the antivenom efficacy against snakes from Southeast Asia (58%), followed by South Asia (35%) and East Asia (19%). Twenty-two (49%) medically important snakes had antivenom(s) with confirmed neutralizing ability. Situation analyses of the availability of effective antivenoms in Asia demonstrated that locally produced antivenoms did not cover all medically important snakes in each country. Among countries without local antivenom production, preclinical studies were conducted only in Bangladesh, Sri Lanka, and Malaysia. Risk of bias assessment was limited in some domains because of unreported data.
CONCLUSIONS/SIGNIFICANCE
Cross-neutralizing of antivenoms against some medically important snakes in Asia was confirmed. This strategy may improve access to geographically effective antivenoms and bypass investment in novel antivenom development, especially in countries without local antivenom production. A database should be developed to aid the development of a snakebite-information system.
Topics: Animals; Antivenins; Snake Bites; Snakes; Sri Lanka; Asia, Eastern
PubMed: 37467278
DOI: 10.1371/journal.pone.0288723 -
Nature Communications Oct 2022The latest SARS-CoV-2 variant of concern Omicron, with its immune escape from therapeutic anti-Spike monoclonal antibodies and WA-1 vaccine-elicited sera, demonstrates...
The latest SARS-CoV-2 variant of concern Omicron, with its immune escape from therapeutic anti-Spike monoclonal antibodies and WA-1 vaccine-elicited sera, demonstrates the continued relevance of COVID-19 convalescent plasma (CCP) therapies. Lessons learnt from previous usage of CCP suggests focusing on early outpatients and immunocompromised recipients, with high neutralizing antibody titer units. Here, we systematically review Omicron-neutralizing plasma activity data, and report that approximately 47% (424/902) of CCP samples from unvaccinated pre-Omicron donors neutralizes Omicron BA.1 with a very low geometric mean of geometric mean titers for 50% neutralization GM(GMT) of ~13, representing a > 20-fold reduction from WA-1 neutralization. Non-convalescent subjects who had received two doses of mRNA vaccines had a GM(GMT50) for Omicron BA.1 neutralization of ~27. However, plasma from vaccinees recovering from either previous pre-Omicron variants of concern infection, Omicron BA.1 infection, or third-dose uninfected vaccinees was nearly 100% neutralizing against Omicron BA.1, BA.2 and BA.4/5 with GM(GMT()) all over 189, 10 times higher than pre-Omicron CCP. Fully vaccinated and post-BA.1 plasma (Vax-CCP) had a GM(GMT) > 450 for BA.4/5 and >1,500 for BA.1 and BA.2. These findings have implications for both CCP stocks collected in prior pandemic periods and for future plans to restart CCP collections. Thus, Vax-CCP provides an effective tool to combat ongoing variants that escape therapeutic monoclonal antibodies.
Topics: Humans; Neutralization Tests; SARS-CoV-2; Antibodies, Viral; COVID-19; Antibodies, Monoclonal; Antibodies, Neutralizing; Spike Glycoprotein, Coronavirus; COVID-19 Serotherapy
PubMed: 36309490
DOI: 10.1038/s41467-022-33864-y -
Transactions of the Royal Society of... Nov 2020Adjunct therapy in snakebite may be lifesaving if administered appropriately or can be harmful if non-judicious use leads to avoidable delays in administering antivenom....
Adjunct therapy in snakebite may be lifesaving if administered appropriately or can be harmful if non-judicious use leads to avoidable delays in administering antivenom. This systematic review analyses the evidence from randomised controlled trials (RCTs) on the efficacy of adjunct treatment administered with antivenom. PubMed, EMBASE, Scopus, Cochrane library and CINAHL were searched for RCTs enrolling patients with snakebite envenoming where a treatment other than antivenom has been assessed for its efficacy within the last 25 y. Fifteen studies met the inclusion criteria. The interventions assessed were categorised as adjunct therapies (heparin or fresh frozen plasma) to reverse haemotoxicity (three studies), antibiotics to prevent local infections (three studies), steroids to reduce local swelling (one study), premedication (adrenaline, steroids and antihistamines, either alone or in combination) to reduce hypersensitivity reactions to antivenom (five studies) and other interventions (three studies). Apart from a beneficial effect of low-dose adrenaline (1:1000, 0.25 ml administered subcutaneously) in preventing antivenom-induced hypersensitivities (OR: 0.54, 95% CI 0.32 to 0.93, two RCTs, 354 participants, moderate certainty evidence) in Sri Lanka, evidence for any other adjunct therapy is either non-existent or needs confirmation by larger better designed trials.
Topics: Anti-Bacterial Agents; Antivenins; Humans; Plasma; Randomized Controlled Trials as Topic; Snake Bites; Sri Lanka
PubMed: 32780827
DOI: 10.1093/trstmh/traa062 -
PLoS Neglected Tropical Diseases Dec 2020Snakebite is a neglected tropical disease with significant morbidity and mortality. Thrombotic microangiopathy (TMA) is an important but poorly understood complication...
Snakebite is a neglected tropical disease with significant morbidity and mortality. Thrombotic microangiopathy (TMA) is an important but poorly understood complication of snakebite associated with acute kidney injury (AKI). Numerous treatments have been attempted based on limited evidence. We conducted a systematic review of TMA following snakebite using a pre-determined case definition of blood film red cell schistocytes or histologically diagnosed TMA. The search strategy included major electronic databases and grey literature. We present a descriptive synthesis for the outcomes of AKI, dialysis free survival (DFS), other end-organ damage, overall survival, and interventions with antivenom and therapeutic plasmapheresis (TPE). This study was prospectively registered with PROSPERO (CRD42019121436). Seventy-two studies reporting 351 cases were included, predominantly small observational studies. Heterogeneity for study selection, design, reporting and outcomes were observed. The commonest envenoming species were hump-nosed vipers (Hypnale spp.), Russell's viper (Daboia russelii) and Australian brown snakes (Pseudechis spp.). The prevalence of TMA was at least 5.4% in proven and probable Hypnale bites, and 10-15% of Australian elapid envenomings, AKI occurred in 94% (293/312) of TMA cases, excluding case reports. The majority of cases with AKI required dialysis. Included prospective and retrospective cohort studies reporting interventions and renal outcomes showed no evidence for benefit from antivenom or TPE with respect to DFS in dialysis dependant AKI. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment for quality of accumulated evidence for interventions was low. The major complication of TMA following snakebite is AKI. AKI improves in most cases. We found no evidence to support benefit from antivenom in snakebite associated TMA, but antivenom remains the standard of care for snake envenoming. There was no evidence for benefit of TPE in snakebite associated TMA, so TPE cannot be recommended. The quality of accumulated evidence was low, highlighting a need for high quality larger studies.
Topics: Acute Kidney Injury; Animals; Antivenins; Australia; Female; Humans; Male; Plasmapheresis; Prevalence; Prospective Studies; Retrospective Studies; Daboia; Snake Bites; Thrombotic Microangiopathies; Viper Venoms
PubMed: 33290400
DOI: 10.1371/journal.pntd.0008936