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Tecovirimat is an antiviral drug approved in 2018 by the United States Food and Drug Administration to treat orthopoxvirus infection. Tecovirimat inhibits orthopoxvirus viral protein (VP) 37, which is involved [...]

Melioidosis is a severe, potentially life-threatening bacterial disease caused by Burkholderia pseudomallei, a gram-negative bacterium found in water and soil in tropical and subtropical environments worldwide (1). Melioidosis might manifest [...]

Despite being one of the earliest diseases described, anthrax, caused by infection with the bacterium Bacillus anthracis, remains a global public health concern, especially in resource-limited, rural agricultural areas, including [...]

The zoonotic disease anthrax, caused by the bacterium Bacillus anthracis, has been known to humankind for thousands of years and is endemic to most continents (1-3). It is a naturally [...]

Burkholderia pseudomallei, which causes melioidosis, is a gram-negative saprophytic bacterium endemic to tropical and subtropical environments worldwide; to our knowledge, isolation from the continental United States has not been reported [...]

Background The high mortality of systemic anthrax is likely a consequence of the severe central nervous system inflammation that occurs in anthrax meningitis. Effective treatment of such infections requires, at a minimum, adequate cerebrospinal fluid (CSF) antimicrobial concentrations. Methods We reviewed English medical literature and regulatory documents to extract information on serum and CSF exposures for antimicrobials with in vitro activity against Bacillus anthracis. Using CSF pharmacokinetic exposures and in vitro B. anthracis susceptibility data, we used population pharmacokinetic modeling and Monte Carlo simulations to determine whether a specific antimicrobial dosage would likely achieve effective CSF antimicrobial activity in patients with normal to inflamed meninges (ie, an intact to markedly disrupted blood–brain barrier). Results The probability of microbiologic success at achievable antimicrobial dosages was high (≥95%) for ciprofloxacin, levofloxacin (500 mg every 12 hours), meropenem, imipenem/cilastatin, penicillin G, ampicillin, ampicillin/sulbactam, doxycycline, and minocycline; acceptable (90%–95%) for piperacillin/tazobactam and levofloxacin (750 mg every 24 hours); and low (<90%) for vancomycin, amikacin, clindamycin, and linezolid. Conclusions Prompt empiric antimicrobial therapy of patients with suspected or confirmed anthrax meningitis may reduce the high morbidity and mortality. Our data support using several β-lactam-, fluoroquinolone-, and tetracycline-class antimicrobials as first-line and alternative agents for treatment of patients with anthrax meningitis; all should achieve effective microbiologic exposures. Our data suggest antimicrobials that should not be relied on to treat suspected or documented anthrax meningitis. Furthermore, the protein synthesis inhibitors clindamycin and linezolid can decrease toxin production and may be useful components of combination therapy. [ABSTRACT FROM AUTHOR]

Anthrax, caused by Bacillus anthracis, is a naturally occurring zoonotic disease of veterinary and public health importance. Anthrax has been reported in wildlife and domestic animals worldwide and can spill [...]

Bacillus anthracis is identified as a select agent subject J-J to select agent regulations (1-3) and as a potential bio-weapon that presents a high risk to the US public (4,5). [...]

Population exposure to aerosolized Bacillus anthracis spores is one of the most potentially catastrophic public health emergencies (1). The 2001 US anthrax attack, in which inhalation anthrax (IA) affected 11 [...]

Background: Historically, malaria has been the predominant cause of acute febrile illness (AFI) in sub-Saharan Africa. However, during the last two decades, malaria incidence has declined due to concerted public health control efforts, including the widespread use of rapid diagnostic tests leading to increased recognition of non-malarial AFI etiologies. Our understanding of non-malarial AFI is limited due to lack of laboratory diagnostic capacity. We aimed to determine the etiology of AFI in three distinct regions of Uganda. Methods: A prospective clinic-based study that enrolled participants from April 2011 to January 2013 using standard diagnostic tests. Participant recruitment was from St. Paul's Health Centre (HC) IV, Ndejje HC IV, and Adumi HC IV in the western, central and northern regions, which differ by climate, environment, and population density. A Pearson's chi-square test was used to evaluate categorical variables, while a two-sample t-test and Krukalis-Wallis test were used for continuous variables. Results: Of the 1281 participants, 450 (35.1%), 382 (29.8%), and 449 (35.1%) were recruited from the western, central, and northern regions, respectively. The median age (range) was 18 (2–93) years; 717 (56%) of the participants were female. At least one AFI pathogen was identified in 1054 (82.3%) participants; one or more non-malarial AFI pathogens were identified in 894 (69.8%) participants. The non-malarial AFI pathogens identified were chikungunya virus, 716 (55.9%); Spotted Fever Group rickettsia (SFGR), 336 (26.2%) and Typhus Group rickettsia (TGR), 97 (7.6%); typhoid fever (TF), 74 (5.8%); West Nile virus, 7 (0.5%); dengue virus, 10 (0.8%) and leptospirosis, 2 (0.2%) cases. No cases of brucellosis were identified. Malaria was diagnosed either concurrently or alone in 404 (31.5%) and 160 (12.5%) participants, respectively. In 227 (17.7%) participants, no cause of infection was identified. There were statistically significant differences in the occurrence and distribution of TF, TGR and SFGR, with TF and TGR observed more frequently in the western region (p = 0.001; p < 0.001) while SFGR in the northern region (p < 0.001). Conclusion: Malaria, arboviral infections, and rickettsioses are major causes of AFI in Uganda. Development of a Multiplexed Point-of-Care test would help identify the etiology of non-malarial AFI in regions with high AFI rates. [ABSTRACT FROM AUTHOR]

Hopefully someone gave you a badger hair brush during the holidays..begins a modern-era advertisement for a purveyor of high-end shaving supplies. Since the turn of the 21st century, there has [...]

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. [ABSTRACT FROM AUTHOR]

Background During an anthrax mass casualty event, prompt identification of patients with anthrax meningitis is important. Previous research has suggested use of a screening tool based on neurological symptoms and signs. Methods Using historical anthrax patient data from 1880 through 2018, we analyzed risk factors for meningitis. We developed lists of symptoms and signs (ie, algorithms) for predicting meningitis with high sensitivity and specificity. We evaluated both single and paired algorithms as screening tools. Results A single algorithm with 1 or more neurological symptoms or signs identifying patients with likely meningitis achieved high sensitivity (86%; 95% confidence interval [CI], 71%–100%) and specificity (90%; 95% CI, 82%–98%). Pairing algorithms with the same symptoms and signs (severe headache, altered mental status, meningeal signs, and "other neurological deficits") improved specificity (99%; 95% CI, 97%–100%) but left 17.3% of patients in a middle "indeterminate" meningitis category and in need of additional diagnostic testing to determine likely meningitis status. Pairing algorithms with differing symptoms and signs also improved specificity over the single algorithm (92%; 95% CI, 85%–99%) but categorized just 2.5% of patients as indeterminate. Conclusions Our study confirms prior research suggesting quick and reliable assessment of patients for anthrax meningitis is possible based on the presence or absence of certain symptoms and signs. A single algorithm was adequate; however, if we assumed low-resource diagnostic testing was feasible for some patients, pairing algorithms improved specificity. Pairing algorithms with differing symptoms and signs minimized the proportion of patients requiring additional diagnostics. [ABSTRACT FROM AUTHOR]

Background US Centers for Disease Control and Prevention guidelines currently recommend triple-therapy antimicrobial treatment for anthrax meningitis. In the Kyrgyz Republic, a country with endemic anthrax, cutaneous anthrax patients are routinely hospitalized and treated successfully with only monotherapy or dual therapy. Clinical algorithms have been developed to identify patients with likely anthrax meningitis based on signs and symptoms alone. We sought to retrospectively identify likely meningitis patients in the Kyrgyz Republic using a clinical algorithm and evaluate risk factors and their outcomes by type of treatment. Methods We conducted a retrospective chart review of cutaneous anthrax patients in the Kyrgyz Republic from 2005 through 2012. Using previous methods, we developed a highly specific algorithm to categorize patients by meningitis status. We then evaluated patient risk factors, treatments, and outcomes by disease severity and meningitis status. Results We categorized 37 of 230 cutaneous anthrax patients as likely having meningitis. All 37 likely meningitis patients survived, receiving only mono- or dual-therapy antimicrobials. We identified underlying medical conditions, such as obesity, hypertension, and chronic obstructive pulmonary disease, and tobacco and alcohol use, as potential risk factors for severe anthrax and anthrax meningitis. Conclusions Based on our analyses, treatment of anthrax meningitis may not require 3 antimicrobials, which could impact future anthrax treatment recommendations. In addition, chronic comorbidities may increase risk for severe anthrax and anthrax meningitis. Future research should further investigate potential risk factors for severe anthrax and their impact on laboratory-confirmed meningitis and evaluate mono- and dual-therapy antimicrobial regimens for anthrax meningitis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Cutaneous anthrax accounts for approximately 95% of anthrax cases worldwide. About 24% of untreated patients die, and many cases are complicated by meningitis. Here, we explore clinical features of cutaneous disease associated with poor outcomes. Methods A systematic review identified 303 full-text articles published from 1950 through 2018 that met predefined inclusion criteria. Cases were abstracted, and descriptive analyses and univariate logistic regression were conducted to identify prognostic indicators for cutaneous anthrax. Results Of 182 included patients, 47 (25.8%) died. Previously reported independent predictors for death or meningitis that we confirmed included fever or chills; nausea or vomiting; headache; severe headache; nonheadache, nonmeningeal signs; leukocytosis; and bacteremia. Newly identified predictors included anxiety, abdominal pain, diastolic hypotension, skin trauma, thoracic edema, malignant pustule edema, lymphadenopathy, and evidence of coagulopathy (all with P <.05). Conclusions We identified patient presentations not previously associated with poor outcomes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Bacillus anthracis, the causative agent of anthrax, is a spore‐forming bacterium that primarily affects herbivorous livestock, wildlife and humans exposed to direct contact with infected animal carcasses or products. To date, there are a limited number of studies that have delineated the potential global distribution of anthrax, despite the importance of the disease from both an economic and public health standpoint. This study compiled occurrence data (n = 874) of confirmed human and animal cases from 1954 to 2021 in 94 countries. Using an ensemble ecological niche model framework, we developed updated maps of the global predicted ecological suitability of anthrax to measure relative risk at multiple scales of analysis, including a model for circumpolar regions. Additionally, we produced maps quantifying the disease transmission risk associated with anthrax to cattle, sheep and goat populations. Environmental suitability for B. anthracis globally is concentred throughout Eurasia, sub‐Saharan Africa, the Americas, Southeast Asia, Australia and Oceania. Suitable environments for B. anthracis at the circumpolar scale extend above the Arctic Circle into portions of Russia, Canada, Alaska and northern Scandinavia. Environmental factors driving B. anthracis suitability globally include vegetation, land surface temperature, soil characteristics, primary climate conditions and topography. At the circumpolar scale, suitability is influenced by soil factors, topography and the derived climate characteristics. The greatest risk to livestock is concentrated within the Indian subcontinent, Australia, Anatolia, the Caucasus region, Central Asia, the European Union, Argentina, Uruguay, China, the United States, Canada and East Africa. This study expands on previous work by providing enhanced knowledge of the potential spatial distribution of anthrax in the Southern Hemisphere, sub‐Saharan Africa, Asia and circumpolar regions of the Northern Hemisphere. We conclude that these updated maps will provide pertinent information to guide disease control programs, inform policymakers and raise awareness at the global level to lessen morbidity and mortality among animals and humans located in environmentally suitable areas. [ABSTRACT FROM AUTHOR]

The impact of highly active antiretroviral therapy (HAART) on hepatitis C virus (HCV) RNA titer and transaminase levels in HIV/HCV-coinfected persons is evaluated for liver transaminase levels, HCV RNA titers and interferon-alpha levels. In conclusion, few patients had drug-induced heptatotoxicity associated with initiation of HAART, but HAART use was not associated with a significant increase in liver transaminase levels for the group as whole.

Objectives. We sought to determine hepatitis B virus (HBV) infection prevalence, associated exposures, and incidence among male inmates at a state correctional facility. Methods. A cross-sectional serological survey was conducted in June 2000, and susceptible inmates were retested in June 2001. Results. At baseline, 230 inmates (20.5%; 95% confidence interval [CI] = 18.2%, 22.9%) exhibited evidence of HBV infection, including 11 acute and 11 chronic infections. Inmates with HBV infection were more likely than susceptible inmates to have injected drugs (38.8% vs 18.0%; adjusted prevalence odds ratio [OR] = 3.0; 95% CI = 1.9, 4.9), to have had more than 25 female sex partners (27.7% vs 17.5%; adjusted prevalence OR = 2.0; 95% CI = 1.4, 3.0), and to have been incarcerated for more than 14 years (38.4% vs 17.6%; adjusted prevalence OR = 1.7; 95% CI = 1.1, 2.6). One year later, 18 (3.6%) showed evidence of new HBV infection. Among 19 individuals with infections, molecular analysis identified 2 clusters involving 10 inmates, each with a unique HBV sequence. Conclusions. We documented ongoing HBV transmission at a state correctional facility. Similar transmission may occur at other US correctional facilities and could be prevented by vaccination of inmates. (Am J Public Health. 2005;95: 1793-1799. doi: 10.2105/AJPH.2004.047753)