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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]

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]

The Global Mycetoma Working Group (GMWG) was formed in January 2018 in response to the declaration of mycetoma as a neglected tropical disease (NTD) by the World Health Assembly. The aim of the working group is to connect experts and public health practitioners around the world to accelerate mycetoma prevention activities and reduce the impact of mycetoma on patients, healthcare providers and society in the endemic regions. The working group has made tangible contributions to mycetoma programming, awareness and coordination among scientists, clinicians and public health professionals. The group's connectivity has enabled rapid response and review of NTD documents in development, has created a network of public health professionals to provide regional mycetoma expertise and has enabled mycetoma to be represented within broader NTD organizations. The GMWG will continue to serve as a hub for networking and building collaborations for the advancement of mycetoma clinical management and treatment, research and public health programming. [ABSTRACT FROM AUTHOR]

Background. Bacillus anthracis, the causative agent of anthrax, is a potential bioterrorism agent. Anthrax meningitis is a common manifestation of B. anthracis infection, has high mortality, and requires more aggressive treatment than anthrax without meningitis. Its rapid identification and treatment are essential for successful management of an anthrax mass casualty incident. Methods. Three hundred six published reports from 1880 through 2013 met predefined inclusion criteria. We calculated descriptive statistics for abstracted cases and conducted multivariable regression on separate derivation and validation cohorts to identify clinical diagnostic and prognostic factors for anthrax meningitis. Results. One hundred thirty-two of 363 (36%) cases with systemic anthrax met anthrax meningitis criteria. Severe headache, altered mental status, meningeal signs, and other neurological signs at presentation independently predicted meningitis in the derivation cohort and were tested as a 4-item assessment tool for use during anthrax mass casualty incidents. Presence of any 1 factor on admission had a sensitivity for finding anthrax meningitis of 89% (83%) in the adult (pediatric) validation cohorts. Anthrax meningitis was unlikely in the absence of any of these signs or symptoms (likelihood ratio [LR]− = 0.12 [0.19] for adult [ pediatric] cohorts), while presence of 2 or more made meningitis very likely (LR+ = 26.5 [30.0]). Survival of anthrax meningitis was predicted by treatment with a bactericidal agent (P = .005) and use of multiple antimicrobials (P = .01). Conclusions. We developed an evidence-based assessment tool for screening patients for meningitis during an anthrax mass casualty incident. Its use could improve both patient outcomes and resource allocation in such an event. [ABSTRACT FROM AUTHOR]

Background. To inform planning for an influenza pandemic, we estimated US demand for N95 filtering facepiece respirators (respirators) by healthcare and emergency services personnel and need for surgical masks by pandemic patients seeking care. Methods. We used a spreadsheet-based model to estimate demand for 3 scenarios of respirator use: base case (usage approximately follows epidemic curve), intermediate demand (usage rises to epidemic peak and then remains constant), and maximum demand (all healthcare workers use respirators from pandemic onset).We assumed that in the base case scenario, up to 16 respirators would be required per day per intensive care unit patient and 8 per day per general ward patient. Outpatient healthcare workers and emergency services personnel would require 4 respirators per day. Patients would require 1.2 surgical masks per day. Results and Conclusions. Assuming that 20% to 30% of the population would become ill, 1.7 to 3.5 billion respirators would be needed in the base case scenario, 2.6 to 4.3 billion in the intermediate demand scenario, and up to 7.3 billion in the maximum demand scenario (for all scenarios, between 0.1 and 0.4 billion surgical masks would be required for patients). For pandemics with a lower attack rate and fewer cases (eg, 2009-like pandemic), the number of respirators needed would be higher because the pandemic would have longer duration. Providing these numbers of respirators and surgical masks represents a logistic challenge for US public health agencies. Public health officials must urgently consider alternative use strategies for respirators and surgical masks during a pandemic that may vary from current practices. [ABSTRACT FROM AUTHOR]

Investigation of melioidosis cases in eastern Puerto Rico revealed high rates of Burkholderia pseudomallei seropositivity, and the bacterium was isolated from soil, suggesting regional endemicity. Increased awareness of melioidosis is needed to enable early case identification and antimicrobial therapy.Background. Melioidosis results from infection with Burkholderia pseudomallei and is associated with case-fatality rates up to 40%. Early diagnosis and treatment with appropriate antimicrobials can improve survival rates. Fatal and nonfatal melioidosis cases were identified in Puerto Rico in 2010 and 2012, respectively, which prompted contact investigations to identify risk factors for infection and evaluate endemicity.Methods. Questionnaires were administered and serum specimens were collected from coworkers, neighborhood contacts within 250 m of both patients' residences, and injection drug user (IDU) contacts of the 2012 patient. Serum specimens were tested for evidence of prior exposure to B. pseudomallei by indirect hemagglutination assay. Neighborhood seropositivity results guided soil sampling to isolate B. pseudomallei.Results. Serum specimens were collected from contacts of the 2010 (n = 51) and 2012 (n = 60) patients, respectively. No coworkers had detectable anti–B. pseudomallei antibody, whereas seropositive results among neighborhood contacts was 5% (n = 2) for the 2010 patient and 23% (n = 12) for the 2012 patient, as well as 2 of 3 IDU contacts for the 2012 case. Factors significantly associated with seropositivity were having skin wounds, sores, or ulcers (odds ratio [OR], 4.6; 95% confidence interval [CI], 1.2–17.8) and IDU (OR, 18.0; 95% CI, 1.6–194.0). Burkholderia pseudomallei was isolated from soil collected in the neighborhood of the 2012 patient.Conclusions. Taken together, isolation of B. pseudomallei from a soil sample and high seropositivity among patient contacts suggest at least regional endemicity of melioidosis in Puerto Rico. Increased awareness of melioidosis is needed to enable early case identification and early initiation of appropriate antimicrobial therapy. [ABSTRACT FROM PUBLISHER]

Background. This article describes transmission of Cryptococcus neoformans by solid organ transplantation. Methods. We reviewed medical records and performed molecular genotyping of isolates to determine potential for donor transmission of Cryptococcus. Results. Cryptococcosis was diagnosed in 3 recipients of organs from a common donor with an undifferentiated neurologic condition at the time of death. Cryptococcal meningoencephalitis was later diagnosed in the donor at autopsy. The liver and 1 kidney recipient developed cryptococcemia and pneumonia and the other kidney recipient developed cryptococcemia and meningitis; 2 patients recovered with prolonged antifungal therapy. We tested 4 recipient isolates with multilocus sequence typing and found they had identical alleles. Conclusions. Our investigation documents the transmission of Cryptococcus neoformans by organ transplantation. Evaluation for cryptococcosis in donors with unexplained neurologic symptoms should be strongly considered. [ABSTRACT FROM AUTHOR]

Summary: Historically, hepatitis A virus (HAV) has been highly prevalent in developing countries, with most infections occurring during childhood, when they are likely to be asymptomatic. Shifts in the acquisition of infection from childhood to adulthood, when clinical hepatitis is more likely, may leave populations vulnerable to large outbreaks. We conducted cross-sectional serosurveys from 1995 to 2008 in four Pacific Island nations to determine the proportion of people previously infected with HAV by measuring antibodies to HAV (anti-HAV). In American Samoa, 0.0% of 4- to 6-year-olds (95% CI 0.0–3.7) were anti-HAV positive. In Chuuk, FSM, 8.6% of 2- to 6-year-olds (95% CI 5.7–11.5) were anti-HAV positive compared with 98.3% of individuals ≥16 years old (95% CI 96.6–100). In Pohnpei, FSM, 0.8% of 2- to 9-year-olds (95% CI 0.0–1.6) were anti-HAV positive compared with 95.1% of ≥16 year-olds (95% CI 92.2–98.0). In RMI, 85.7% (95% CI 81.9–89.5) of 4- to 9-year-olds were anti-HAV positive. In Palau, 0.7% of 7- to 8-year-olds were anti-HAV positive (95% CI 0.0–1.8). The low HAV seroprevalence among children in American Samoa, FSM and Palau may indicate a vulnerability to hepatitis A morbidity among these populations. These data will be useful for evaluating the need for hepatitis A surveillance and vaccination programs. [Copyright &y& Elsevier]

Background. Severe liver injuries were attributed to the rifampin and pyrazinamide (RZ) regimen after it was recommended for treating latent tuberculosis infection. Implicating RZ as the likeliest cause required excluding alternative causes. Methods. US health departments reported data on patients who died or were hospitalized for liver disease within 1 month after taking RZ for latent tuberculosis infection from October 1998 through March 2004. The circumstances were investigated on site for each case. Illness characteristics, reasons for RZ treatment, doses and frequency of administration of pyrazinamide, monitoring during treatment, and causes of liver injury were determined. Results. Liver injury was attributable to RZ use for all 50 patients reported, 12 of whom died. For 47 patients, RZ was the likeliest cause of liver injury. The median patient age was 44 years (range, 17-73 years). Thirty-two patients (64%) were male. Seven (16%) of 43 patients tested had hepatitis C virus antibodies, 1 (2%) of 45 had chronic hepatitis B, 3 (14%) of 22 had positive results of HIV serologic tests, 34 (71%) of 48 had alcohol use noted, and 33 (66%) of 50 were taking additional hepatotoxic medications. Six patients, 2 of whom died, had no predictors for liver disease. Patients who died were older (median age, 52 vs. 42 years; P = .08) and took a greater number of other medications (median number of medications, 4 vs. 2; P = .05) than did those who recovered, but these 2 factors were correlated (P<.01). Thirty-one patients (62%) were monitored according to guidelines, 9 of whom died. Conclusions. RZ was the likeliest cause of most of these liver injuries, some of which were fatal in spite of monitoring. Fatality was predicted by age or use of other medications, but none of the cofactors showed promise as a reliable clinical predictor of severe liver injury. [ABSTRACT FROM AUTHOR]

Presents information on a matched case-control study which determined the association of foods containing green onion and illness. Outbreaks of foodborne hepatitis A virus; Methodology; Results.

Examines the duration of viremia and the time course for the development of immunoglobulin M antibodies in natural and experimental hepatitis A virus infection among men and chimpanzees. Nested reverse-transcriptase polymerase chain reaction analysis; Enzyme-linked immunosorbent assay; Relationship between detection of hepatitis A virus RNA and levels of antibody and liver enzyme in serum.

Objective Following Hurricanes Irma and Maria, the first case of human leptospirosis ever identified in the US Virgin Islands (USVI) was reported to the Virgin Islands Department of Health. Leptospirosis is a potentially fatal bacterial disease caused by Leptospira species found in animal urine and urine-contaminated water and soil. Outbreaks can occur following extreme weather events. Method Additional cases of leptospirosis were identified in the 2.5 months post-hurricanes by reviewing emergency department (ED) records from territorial hospitals for patients demonstrating leptospirosis-consistent symptoms, testing symptomatic patients previously enrolled in the USVI arbovirus surveillance system (VIASS), and adding leptospirosis testing prospectively to VIASS. Available patient sera underwent local rapid diagnostic testing for anti- Leptospira IgM followed by confirmatory microscopic agglutination testing at the US Centers for Disease Control and Prevention. Water was collected from cisterns with epidemiologic links to confirmed cases and tested by real-time PCR (qPCR) for pathogenic Leptospira spp. Results Sixteen retrospectively identified symptomatic patients were enrolled in VIASS; 15 with available samples tested negative. Based on review of 5226 ED charts, 6 patients were further investigated; of these, 5 were tested of which 1 was positive. Prospective leptospirosis surveillance tested 57 additional patients; of these, 1 was positive. Water from 1 of 5 tested cisterns was found positive by qPCR. Conclusions This investigation documents the first 3 cases of leptospirosis reported in the USVI and demonstrates how VIASS successfully was adapted to establish leptospirosis surveillance. Contaminated cistern water was identified as a potential source for Leptospira spp. transmission, highlighting the need for additional post-hurricane remediation and disinfection guidance. [ABSTRACT FROM AUTHOR]

Melioidosis is caused by the gram-negative bacillus Burkholderia pseudomallei, endemic to northern Australia and Southeast Asia. We present a patient who traveled to Mexico, returned to the United States, and developed progressive manifestations of melioidosis, culminating as central nervous system disease. Standard therapy was contraindicated, and a prolonged intensive phase was employed. [ABSTRACT FROM AUTHOR]