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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 -
Clinical Infectious Diseases : An... Oct 2022Bacillus anthracis can cause anthrax and is a potential bioterrorism agent. The 2014 Centers for Disease Control and Prevention recommendations for medical... (Review)
Review
BACKGROUND
Bacillus anthracis can cause anthrax and is a potential bioterrorism agent. The 2014 Centers for Disease Control and Prevention recommendations for medical countermeasures against anthrax were based on in vitro data and expert opinion. However, a century of previously uncompiled observational human data that often includes treatment and outcomes is available in the literature for analysis.
METHODS
We reviewed treatment outcomes for patients hospitalized with anthrax. We stratified patients by meningitis status, route of infection, and systemic criteria, then analyzed survival by treatment type, including antimicrobials, antitoxin/antiserum, and steroids. Using logistic regression, we calculated odds ratios and 95% confidence intervals to compare survival between treatments. We also calculated hospital length of stay. Finally, we evaluated antimicrobial postexposure prophylaxis (PEPAbx) using data from a 1970 Russian-language article.
RESULTS
We identified 965 anthrax patients reported from 1880 through 2018. After exclusions, 605 remained: 430 adults, 145 children, and 30 missing age. Survival was low for untreated patients and meningitis patients, regardless of treatment. Most patients with localized cutaneous or nonmeningitis systemic anthrax survived with 1 or more antimicrobials; patients with inhalation anthrax without meningitis fared better with at least 2. Bactericidal antimicrobials were effective for systemic anthrax; addition of a protein synthesis inhibitor(s) (PSI) to a bactericidal antimicrobial(s) did not improve survival. Likewise, addition of antitoxin/antiserum to antimicrobials did not improve survival. Mannitol improved survival for meningitis patients, but steroids did not. PEPAbx reduced risk of anthrax following exposure to B. anthracis.
CONCLUSIONS
Combination therapy appeared to be superior to monotherapy for inhalation anthrax without meningitis. For anthrax meningitis, neither monotherapy nor combination therapy were particularly effective; however, numbers were small. For localized cutaneous anthrax, monotherapy was sufficient. For B. anthracis exposures, PEPAbx was effective.
Topics: Adult; Anthrax; Anti-Bacterial Agents; Anti-Infective Agents; Antitoxins; Bacillus anthracis; Biological Warfare Agents; Bioterrorism; Child; Hospitals; Humans; Mannitol; Protein Synthesis Inhibitors; Respiratory Tract Infections; Treatment Outcome
PubMed: 36251553
DOI: 10.1093/cid/ciac536 -
The Cochrane Database of Systematic... Apr 2009Anthrax is a bacterial zoonosis that occasionally causes human disease and is potentially fatal. Anthrax vaccines include a live-attenuated vaccine, an alum-precipitated... (Review)
Review
BACKGROUND
Anthrax is a bacterial zoonosis that occasionally causes human disease and is potentially fatal. Anthrax vaccines include a live-attenuated vaccine, an alum-precipitated cell-free filtrate vaccine, and a recombinant protein vaccine.
OBJECTIVES
To evaluate the effectiveness, immunogenicity, and safety of vaccines for preventing anthrax.
SEARCH STRATEGY
We searched the following databases (November 2008): Cochrane Infectious Diseases Group Specialized Register; CENTRAL (The Cochrane Library 2008, Issue 4); MEDLINE; EMBASE; LILACS; and mRCT. We also searched reference lists.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) of individuals and cluster-RCTs comparing anthrax vaccine with placebo, other (non-anthrax) vaccines, or no intervention; or comparing administration routes or treatment regimens of anthrax vaccine.
DATA COLLECTION AND ANALYSIS
Two authors independently considered trial eligibility, assessed risk of bias, and extracted data. We presented cases of anthrax and seroconversion rates using risk ratios (RR) and 95% confidence intervals (CI). We summarized immunoglobulin G (IgG) concentrations using geometric means. We carried out a sensitivity analysis to investigate the effect of clustering on the results from one cluster-RCT. No meta-analysis was undertaken.
MAIN RESULTS
One cluster-RCT (with 157,259 participants) and four RCTs of individuals (1917 participants) met the inclusion criteria. The cluster-RCT from the former USSR showed that, compared with no vaccine, a live-attenuated vaccine (called STI) protected against clinical anthrax whether given by a needleless device (RR 0.16; 102,737 participants, 154 clusters) or the scarification method (RR 0.25; 104,496 participants, 151 clusters). Confidence intervals were statistically significant in unadjusted calculations, but when a small amount of association within clusters was assumed, the differences were not statistically significant. The four RCTs (of individuals) of inactivated vaccines (anthrax vaccine absorbed and recombinant protective antigen) showed a dose response relationship for the anti-protective antigen IgG antibody titre. Intramuscular administration was associated with fewer injection site reactions than subcutaneous injection, and injection site reaction rates were lower when the dosage interval was longer.
AUTHORS' CONCLUSIONS
One cluster-RCT provides limited evidence that a live-attenuated vaccine is effective in preventing cutaneous anthrax. Vaccines based on anthrax antigens are immunogenic in most vaccinees with few adverse events or reactions. Ongoing randomized controlled trials are investigating the immunogenicity and safety of anthrax vaccines.
Topics: Anthrax; Anthrax Vaccines; Humans; Randomized Controlled Trials as Topic; Vaccines, Attenuated
PubMed: 19370633
DOI: 10.1002/14651858.CD006403.pub2 -
Health Security 2015Concern about use of anthrax as a bioweapon prompted development of novel anthrax antitoxins for treatment. Clinical guidelines for the treatment of anthrax recommend... (Review)
Review
Concern about use of anthrax as a bioweapon prompted development of novel anthrax antitoxins for treatment. Clinical guidelines for the treatment of anthrax recommend antitoxin therapy in combination with intravenous antimicrobials; however, a large-scale or mass anthrax incident may exceed antitoxin availability and create a need for judicious antitoxin use. We conducted a systematic review of antitoxin treatment of inhalation anthrax in humans and experimental animals to inform antitoxin recommendations during a large-scale or mass anthrax incident. A comprehensive search of 11 databases and the FDA website was conducted to identify relevant animal studies and human reports: 28 animal studies and 3 human cases were identified. Antitoxin monotherapy at or shortly after symptom onset demonstrates increased survival compared to no treatment in animals. With early treatment, survival did not differ between antimicrobial monotherapy and antimicrobial-antitoxin therapy in nonhuman primates and rabbits. With delayed treatment, antitoxin-antimicrobial treatment increased rabbit survival. Among human cases, addition of antitoxin to combination antimicrobial treatment was associated with survival in 2 of the 3 cases treated. Despite the paucity of human data, limited animal data suggest that adjunctive antitoxin therapy may improve survival. Delayed treatment studies suggest improved survival with combined antitoxin-antimicrobial therapy, although a survival difference compared with antimicrobial therapy alone was not demonstrated statistically. In a mass anthrax incident with limited antitoxin supplies, antitoxin treatment of individuals who have not demonstrated a clinical benefit from antimicrobials, or those who present with more severe illness, may be warranted. Additional pathophysiology studies are needed, and a point-of-care assay correlating toxin levels with clinical status may provide important information to guide antitoxin use during a large-scale anthrax incident.
Topics: Administration, Intravenous; Animals; Anthrax; Anti-Bacterial Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antigens, Bacterial; Antitoxins; Bioterrorism; Drug Therapy, Combination; Humans; Immunoglobulin G; Immunoglobulins, Intravenous; Mass Casualty Incidents; Rabbits; Respiratory Tract Infections
PubMed: 26690378
DOI: 10.1089/hs.2015.0032 -
International Journal of Environmental... Mar 2023To understand existing triage algorithms, propose improvement measures through comparison to better deal with mass-casualty incidents caused by bioterrorism. (Review)
Review
OBJECTIVES
To understand existing triage algorithms, propose improvement measures through comparison to better deal with mass-casualty incidents caused by bioterrorism.
STUDY DESIGN
Systematic review.
METHODS
Medline, Scopus and Web of Science were searched up to January 2022. The studies investigating triage algorithms for mass-casualty bioterrorism. Quality assessment was performed using the International Narrative Systematic Assessment tool. Data extractions were performed by four reviewers.
RESULTS
Of the 475 titles identified in the search, 10 studies were included. There were four studies on triage algorithms for most bioterrorism events, four studies on triage algorithms for anthrax and two studies on triage algorithms for mental or psychosocial problems caused by bioterrorism events. We introduced and compared 10 triage algorithms used for different bioterrorism situations.
CONCLUSION
For triage algorithms for most bioterrorism events, it is necessary to determine the time and place of the attack as soon as possible, control the number of exposed and potentially exposed people, prevent infection and determine the type of biological agents used. Research on the effects of decontamination on bioterrorism attacks needs to continue. For anthrax triage, future research should improve the distinction between inhalational anthrax symptoms and common disease symptoms and improve the efficiency of triage measures. More attention should be paid to triage algorithms for mental or psychosocial problems caused by bioterrorism events.
Topics: Humans; Triage; Bioterrorism; Anthrax; Mass Casualty Incidents; Algorithms
PubMed: 36981980
DOI: 10.3390/ijerph20065070 -
Euro Surveillance : Bulletin Europeen... Apr 2011In order to assist national public health authorities in the European Union to assess the risks associated with the transmission of infectious agents on board aircrafts,... (Review)
Review
In order to assist national public health authorities in the European Union to assess the risks associated with the transmission of infectious agents on board aircrafts, the European Centre for Disease Prevention and Control initiated in 2007 the RAGIDA project (Risk Assessment Guidance for Infectious Diseases transmitted on Aircraft). RAGIDA consists of two parts: the production of a systematic review and a series of disease-specific guidance documents. The systematic review covered over 3,700 peer-reviewed articles and grey literature for the following diseases: tuberculosis, influenza, severe acute respiratory syndrome (SARS), invasive meningococcal disease, measles, rubella, diphtheria, Ebola and Marburg haemorrhagic fevers, Lassa fever, smallpox and anthrax. In addition, general guidelines on risk assessment and management from international aviation boards and national and international public health agencies were systematically searched. Experts were interviewed on case-based events by standardised questionnaires. Disease-specific guidance documents on tuberculosis, SARS, meningococcal infections, measles, rubella, Ebola and Marburg haemorrhagic fevers, Lassa fever, smallpox and anthrax were the result of consultations of disease-specific expert panels. Factors that influence the risk assessment of infectious disease transmission on board aircrafts and decision making for contact tracing are outlined.
Topics: Aircraft; Communicable Diseases; Europe; European Union; Guidelines as Topic; Humans; Risk Assessment; Travel
PubMed: 21527131
DOI: No ID Found -
PLoS Neglected Tropical Diseases Oct 2022Zoonoses can cause a substantial burden on both human and animal health. Globally, estimates of the dual (human and animal) burden of zoonoses are scarce. Therefore,...
BACKGROUND
Zoonoses can cause a substantial burden on both human and animal health. Globally, estimates of the dual (human and animal) burden of zoonoses are scarce. Therefore, this study aims to quantify the dual burden of zoonoses using a comparable metric, "zoonosis Disability Adjusted Life Years" (zDALY).
METHODOLOGY
We systematically reviewed studies that quantify in the same article zoonoses in animals, through monetary losses, and in humans in terms of Disability Adjusted Life Years (DALYs). We searched EMBASE, Web of Science, Scopus, PubMed, and Google Scholar. We excluded articles that did not provide the data to estimate the zDALY or those for which full text was not available. This study was registered at PROSPERO, CRD42022313081.
PRINCIPAL FINDINGS/SIGNIFICANCE
We identified 512 potentially eligible records. After deduplication and screening of the title and abstract, 23 records were assessed for full-text review. Fourteen studies were included in this systematic review. The data contains estimates from 10 countries, a study at continental level (Asia and Africa), and 2 studies on a global scale. Rabies was the most frequently reported zoonosis where zDALYs were calculated, based on the following included studies: for Kazakhstan 457 (95% CI 342-597), Viet Nam 5316 (95% CI 4382-6244), Asia 1,145,287 (90% CI 388,592-1,902,310), Africa 837,158 (90% CI 283,087-1,388,963), and worldwide rabies 5,920,014 (95% CI 1,547,860-10,290,815). This was followed by echinococcosis, the zDALYs in Peru were 2238 (95% CI 1931-2546), in China 1490 (95% CI 1442-1537), and worldwide cystic echinococcosis 5,935,463 (95% CI 4,497,316-7,377,636). Then, the zDALYs on cysticercosis for Mozambique were 2075 (95% CI 1476-2809), Cameroon 59,540 (95% CR 16,896-101,803), and Tanzania 34,455 (95% CI 12,993-76,193). Brucellosis in Kazakhstan were 2443 zDALYs (95% CI 2391-2496), and brucellosis and anthrax in Turkey 3538 zDALYs (95% CI 2567-6706). Finally, zDALYs on leptospirosis in New Zealand were 196, and Q fever in Netherlands 2843 (95% CI 1071-4603). The animal burden was superior to the human burden in the following studies: worldwide cystic echinococcosis (83%), brucellosis in Kazakhstan (71%), leptospirosis in New Zealand (91%), and brucellosis, and anthrax in Turkey (52%). Countries priorities on zoonoses can change if animal populations are taken into consideration.
Topics: Animals; Humans; Rabies; Anthrax; Zoonoses; Brucellosis; Echinococcosis; Leptospirosis; Tanzania
PubMed: 36240240
DOI: 10.1371/journal.pntd.0010540 -
IJID Regions Jun 2023Population factors such as urbanization, socio-economic, and environmental factors are driving forces for emerging/re-emerging zoonotic diseases in Cameroon. To inform... (Review)
Review
INTRODUCTION
Population factors such as urbanization, socio-economic, and environmental factors are driving forces for emerging/re-emerging zoonotic diseases in Cameroon. To inform preparedness and prioritization efforts, this study mapped out epidemiological data (including prevalence) of zoonotic diseases occurring in Cameroon between 2000 and 2022 by demographic factors.
METHODS
Following the PRISMA guidelines, a protocol was registered in the PROSPERO database (CRD42022333059). Independent reviewers searched the PubMed, Embase, CINAHL, Cochrane, and Scopus databases on May 30, 2022 for relevant articles; duplicates were removed, and the titles, abstracts, and full texts were screened to identify eligible articles.
RESULTS
Out of 4142 articles identified, 64 eligible articles were retrieved in the database search and an additional 12 from the cited literature ( = 76). Thirty-five unique zoonoses (viral, bacterial, and parasitic) were indexed, including Cameroon priority zoonoses: anthrax, bovine tuberculosis, Ebola and Marburg virus disease, highly pathogenic avian influenza, and rabies. The number of studies varied by region, ranging from 12 in the Far North to 32 in the Centre Region. The most reported were as follows: brucellosis (random-effects pooled estimate proportion (effect size), ES 0.05%, 95% confidence interval (CI) 0.03-0.07; = 6), dengue (ES 0.13%, 95% CI 0.06-0.22; = 12), avian and swine influenza virus (ES 0.10%, 95% CI 0.04-0.20; = 8), and toxoplasmosis (ES 0.49%, 95% CI 0.35-0.63; = 11), although values were greater than 75%, thus there was high inter-study heterogeneity ( < 0.01).
CONCLUSIONS
This understanding of the distribution of emerging and re-emerging zoonotic threats in Cameroon is vital to effective preventive and resource prioritization measures.
PubMed: 37009575
DOI: 10.1016/j.ijregi.2022.12.001 -
One Health (Amsterdam, Netherlands) Jun 2023The disease anthrax occurs generally in herbivores and the causative organism () infects humans who come in contact with infected animals or their products The... (Review)
Review
The disease anthrax occurs generally in herbivores and the causative organism () infects humans who come in contact with infected animals or their products The persistence of anthrax spores for decades and its lethality contribute to its biowarfare potential. We conducted this systematic review along with risk mapping to investigate the spatio-temporal distribution, clinico-epidemiological, socio-behavioural and programmatic issues pertaining to anthrax in India over the last two decades. Peer reviewed quantitative and qualitative studies and grey literature comprising weekly reports of the 'Integrated Disease Surveillance Program' (IDSP), were accessed for extracting data. IDSP data were used for geo-referencing of the villages of anthrax cases; Pseudo-absence was generated to fit a Bayesian Additive Regression Trees (BART) model to develop anthrax risk map. The case fatality rate of cutaneous anthrax ranged from 2% to 38%, while the gastrointestinal and inhalational types were 100% fatal. Our synthesis revealed that human anthrax outbreaks in India were clustered around the eastern coastal regions. The states of Odisha, West Bengal, Andhra Pradesh and Jharkhand reported maximum number of outbreaks. Odisha reported a maximum number of 439 human anthrax cases since 2009, of which Koraput district contributed to 200 cases (46%). While handling or consumption of infected animal product were proximal drivers of these events, poverty, lack of awareness, traditional beliefs and local practices served as facilitatory factors. Other structural determinants were wild life-livestock interface, historical forest loss, soil pH, soil-water balance, organic carbon content, temperature, rainfall and humidity. The programmatic issues identified through this review were lack of active surveillance, non-availability of diagnostic facility at the periphery, delayed reporting, absence of routine livestock vaccination and lack of adequate veterinary services. Interventions based on One-health approach in the country merit immediate policy and program attention; high risk zones for anthrax identified during present investigation, should be prioritized.
PubMed: 37363236
DOI: 10.1016/j.onehlt.2023.100564 -
Clinical Infectious Diseases : An... Oct 2022Anthrax is endemic to many countries, including the United States. The causative agent, Bacillus anthracis, poses a global bioterrorism threat. Without effective... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anthrax is endemic to many countries, including the United States. The causative agent, Bacillus anthracis, poses a global bioterrorism threat. Without effective antimicrobial postexposure prophylaxis (PEPAbx) and treatment, the mortality of systemic anthrax is high. To inform clinical guidelines for PEPAbx and treatment of B. anthracis infections in humans, we systematically evaluated animal anthrax treatment model studies.
METHODS
We searched for survival outcome data in 9 scientific search engines for articles describing antimicrobial PEPAbx or treatment of anthrax in animals in any language through February 2019. We performed meta-analyses of efficacy of antimicrobial PEPAbx and treatment for each drug or drug combination using random-effects models. Pharmacokinetic/pharmacodynamic relationships were developed for 5 antimicrobials with available pharmacokinetic data. Monte Carlo simulations were used to predict unbound drug exposures in humans.
RESULTS
We synthesized data from 34 peer-reviewed studies with 3262 animals. For PEPAbx and treatment of infection by susceptible B. anthracis, effective monotherapy can be accomplished with fluoroquinolones, tetracyclines, β-lactams (including penicillin, amoxicillin-clavulanate, and imipenem-cilastatin), and lipopeptides or glycopeptides. For naturally occurring strains, unbound drug exposures in humans were predicted to adequately cover the minimal inhibitory concentrations (MICs; those required to inhibit the growth of 50% or 90% of organisms [MIC50 or MIC90]) for ciprofloxacin, levofloxacin, and doxycycline for both the PEPAbx and treatment targets. Dalbavancin covered its MIC50 for PEPAbx.
CONCLUSIONS
These animal studies show many reviewed antimicrobials are good choices for PEPAbx or treatment of susceptible B. anthracis strains, and some are also promising options for combating resistant strains. Monte Carlo simulations suggest that oral ciprofloxacin, levofloxacin, and doxycycline are particularly robust choices for PEPAbx or treatment.
Topics: Amoxicillin-Potassium Clavulanate Combination; Animals; Anthrax; Anti-Bacterial Agents; Anti-Infective Agents; Bacillus anthracis; Cilastatin, Imipenem Drug Combination; Ciprofloxacin; Doxycycline; Glycopeptides; Humans; Levofloxacin; Lipopeptides; Models, Animal; Tetracyclines; United States; beta-Lactams
PubMed: 36251546
DOI: 10.1093/cid/ciac591