Risk Factors for Death or Meningitis in Adults Hospitalized for Cutaneous Anthrax, 1950-2018: A Systematic Review.

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.

Algorithms for the Identification of Anthrax Meningitis During a Mass Casualty Event Based on a Systematic Review of Systemic Anthrax From 1880 Through 2018.

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.

Updated Review on Nocardia Species: 2006-2021.

This review serves as an update to the previous Nocardia review by Brown-Elliott et al. published in 2006 (B. A. Brown-Elliott, J. M. Brown, P. S. Conville, and R. J. Wallace. Jr., Clin Microbiol Rev 19:259-282, 2006, https://doi.org/10.1128/CMR.19.2.259-282.2006). Included is a discussion on the taxonomic expansion of the genus, current identification methods, and the impact of new technology (including matrix-assisted laser desorption ionization-time of flight [MALDI-TOF] and whole genome sequencing) on diagnosis and treatment. Clinical manifestations, the epidemiology, and geographic distribution are briefly discussed. An additional section on actinomycotic mycetoma is added to address this often-neglected disease.

Epidemiologic Investigation of Two Welder's Anthrax Cases Caused by Bacillus Cereus Group Bacteria: Occupational Link Established by Environmental Detection.

Abstract Bacillus cereus group bacteria containing the anthrax toxin genes can cause fatal anthrax pneumonia in welders. Two welder's anthrax cases identified in 2020 were investigated to determine the source of each patient's exposure. Environmental sampling was performed at locations where each patient had recent exposure to soil and dust. Samples were tested for the anthrax toxin genes by real-time PCR, and culture was performed on positive samples to identify whether any environmental isolates matched the patient's clinical isolate. A total of 185 environmental samples were collected in investigation A for patient A and 108 samples in investigation B for patient B. All samples from investigation B were real-time PCR-negative, but 14 (8%) samples from investigation A were positive, including 10 from patient A's worksite and 4 from his work-related clothing and gear. An isolate genetically matching the one recovered from patient A was successfully cultured from a worksite soil sample. All welder's anthrax cases should be investigated to determine the source of exposure, which may be linked to their worksite. Welding and metalworking employers should consider conducting a workplace hazard assessment and implementing controls to reduce the risk of occupationally associated illnesses including welder's anthrax.

What Is Anthrax?

Anthrax has been feared for its high mortality in animals and humans for centuries. The etiologic agent is considered a potentially devastating bioweapon, and since 1876-when Robert Koch demonstrated that Bacillus anthracis caused anthrax-it has been considered the sole cause of the disease. Anthrax is, however, a toxin-mediated disease. The toxins edema toxin and lethal toxin are formed from protein components encoded for by the pXO1 virulence plasmid present in pathogenic B. anthracis strains. However, other members of the Bacillus cereus group, to which B. anthracis belongs, have recently been shown to harbor the pXO1 plasmid and produce anthrax toxins. Infection with these Bacillus cereus group organisms produces a disease clinically similar to anthrax. This suggests that anthrax should be defined by the exotoxins encoded for by the pXO1 plasmid rather than the bacterial species it has historically been associated with, and that the definition of anthrax should be expanded to include disease caused by any member of the B. cereus group containing the toxin-producing pXO1 plasmid or anthrax toxin genes specifically.

Ecological Niche Model of Bacillus cereus Group Isolates Containing a Homologue of the pXO1 Anthrax Toxin Genes Infecting Metalworkers in the United States.

While Bacillus cereus typically causes opportunistic infections in humans, within the last three decades, severe and fatal infections caused by isolates of the B. cereus group harboring anthrax toxin genes have been reported in the United States. From 1994 to 2020, seven cases of anthrax-like illness resulting from these isolates have been identified. With one exception, the cases have occurred in the Gulf States region of the United States among metalworkers. We aimed to develop an ecological niche model (ENM) to estimate a spatial area conducive to the survival of these organisms based on the presence of known human infections and environmental variables. The estimated ecological niche for B. cereus was modeled with the maximum entropy algorithm (Maxent). Environmental variables contributing most to the model were soil characteristics (cation exchange capacity, carbon content, soil pH), temperature, enhanced vegetation index (EVI), and land surface temperature (LST). Much of the suitable environments were located throughout the Gulf Coast Plain, Texas Backland Prairies, East Central Texas Plains, Edwards Plateau, Cross Timbers, Mississippi Alluvial Plain, and Central Great Plains. These findings may provide additional guidance to narrow potential risk areas to efficiently communicate messages to metalworkers and potentially identify individuals who may benefit from the anthrax vaccine.

High Case-Fatality Rate for Human Anthrax, Northern Ghana, 2005-2016.

The human cutaneous anthrax case-fatality rate is ≈1% when treated, 5%-20% when untreated. We report high case-fatality rates (median 35.0%; 95% CI 21.1%-66.7%) during 2005-2016 linked to livestock handling in northern Ghana, where veterinary resources are limited. Livestock vaccination and access to human treatment should be evaluated.

Development of the Global Mycetoma Working Group.

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.

Control and Prevention of Anthrax, Texas, USA, 2019.

The zoonotic disease anthrax is endemic to most continents. It is a disease of herbivores that incidentally infects humans through contact with animals that are ill or have died from anthrax or through contact with Bacillus anthracis-contaminated byproducts. In the United States, human risk is primarily associated with handling carcasses of hoofstock that have died of anthrax; the primary risk for herbivores is ingestion of B. anthracis spores, which can persist in suitable alkaline soils in a corridor from Texas through Montana. The last known naturally occurring human case of cutaneous anthrax associated with livestock exposure in the United States was reported from South Dakota in 2002. Texas experienced an increase of animal cases in 2019 and consequently higher than usual human risk. We describe the animal outbreak that occurred in southwest Texas beginning in June 2019 and an associated human case. Primary prevention in humans is achieved through control of animal anthrax.

Rat-Bite Fever in the United States: An Analysis Using Multiple National Data Sources, 2001-2015.

BACKGROUND: Rat-bite fever is a rare disease associated with rat bites or direct/indirect rodent contact. METHODS: We examined rat-bite fever and rat-bite injury diagnoses in the United States during 2001-2015. We analyzed national, state, and Indian Health Service healthcare encounter datasets for rat-bite fever and rat-bite injury diagnoses. We calculated average-annual encounter rates per 1 000 000 persons. RESULTS: Nationally, the rat-bite fever Emergency Department visit rate was 0.33 (95% confidence interval [CI], 0.19-0.47) and the hospitalization rate was 0.20 (95% CI, 0.17-0.24). The rat-bite injury Emergency Department visit rate was 10.51 (95% CI, 10.13-10.88) and the hospitalization rate was 0.27 (95% CI, 0.23-0.30). The Indian Health Service Emergency Department/outpatient visit rate was 3.00 for rat-bite fever and 18.89 for rat-bite injury. The majority of rat-bite fever encounters were among individuals 0-19 years of age. CONCLUSIONS: Our results support the literature that rat-bite fever is rare and affects children and young adults. Targeted education could benefit specific risk groups.

Potential distributions of Bacillus anthracis and Bacillus cereus biovar anthracis causing anthrax in Africa.

BACKGROUND: Bacillus cereus biovar anthracis (Bcbva) is an emergent bacterium closely related to Bacillus anthracis, the etiological agent of anthrax. The latter has a worldwide distribution and usually causes infectious disease in mammals associated with savanna ecosystems. Bcbva was identified in humid tropical forests of Côte d'Ivoire in 2001. Here, we characterize the potential geographic distributions of Bcbva in West Africa and B. anthracis in sub-Saharan Africa using an ecological niche modeling approach. METHODOLOGY/PRINCIPAL FINDINGS: Georeferenced occurrence data for B. anthracis and Bcbva were obtained from public data repositories and the scientific literature. Combinations of temperature, humidity, vegetation greenness, and soils values served as environmental variables in model calibrations. To predict the potential distribution of suitable environments for each pathogen across the study region, parameter values derived from the median of 10 replicates of the best-performing model for each pathogen were used. We found suitable environments predicted for B. anthracis across areas of confirmed and suspected anthrax activity in sub-Saharan Africa, including an east-west corridor from Ethiopia to Sierra Leone in the Sahel region and multiple areas in eastern, central, and southern Africa. The study area for Bcbva was restricted to West and Central Africa to reflect areas that have likely been accessible to Bcbva by dispersal. Model predicted values indicated potential suitable environments within humid forested environments. Background similarity tests in geographic space indicated statistical support to reject the null hypothesis of similarity when comparing environments associated with B. anthracis to those of Bcbva and when comparing humidity values and soils values individually. We failed to reject the null hypothesis of similarity when comparing environments associated with Bcbva to those of B. anthracis, suggesting that additional investigation is needed to provide a more robust characterization of the Bcbva niche. CONCLUSIONS/SIGNIFICANCE: This study represents the first time that the environmental and geographic distribution of Bcbva has been mapped. We document likely differences in ecological niche-and consequently in geographic distribution-between Bcbva and typical B. anthracis, and areas of possible co-occurrence between the two. We provide information crucial to guiding and improving monitoring efforts focused on these pathogens.

Knowledge, attitudes, and practices related to anthrax and animal care: A case-control study in Georgia.

INTRODUCTION: Anthrax is endemic in Georgia and recent outbreaks prompted a livestock-handler case-control study with a component to evaluate anthrax knowledge, attitudes, and practices (KAP) among livestock handlers or owners. METHODS: Cases were handlers of livestock with confirmed animal anthrax from June 2013-May 2015. Handlers of four matched unaffected animals were selected as controls, two from the same village as the case animal ("village control") and two from 3-10 km away ("area control"). Descriptive statistics were reported and conditional logistic regression was performed to estimate the magnitude of the association of cases with specific study KAP factors. RESULTS: Cases were more likely male, had lower level college education, less animal care experience, and provided more animal care to their cattle. Cases had lower odds of burying a suddenly dead animal compared to all controls (Odds Ratio [OR]: 0.32, 95% Confidence interval [CI]:0.12, 0.88) and area controls (OR: 0.32, 95% CI: 0.11, 0.91). On an 8-point knowledge scale, cases having an animal with anthrax had a 1.31 times greater knowledge score compared to all controls (95% CI: 1.03, 1.67). Cases had higher odds of ever having human anthrax or knowing another person who had anthrax compared to all controls (OR: 4.56, 95% CI: 1.45, 14.30) and area controls (OR: 7.16, 95% CI: 1.52, 33.80). DISCUSSION: Cases were more knowledgeable of anthrax and had better anthrax prevention practices, but these are likely a result of the case investigation and ring vaccination following the death of their animal. CONCLUSIONS: The findings reveal a low level of knowledge and practices related to anthrax control and prevention, and will guide educational material development to fill these gaps.

Risk factors associated with the occurrence of anthrax outbreaks in livestock in the country of Georgia: A case-control investigation 2013-2015.

INTRODUCTION: Anthrax is considered endemic in livestock in Georgia. In 2007, the annual vaccination became the responsibility of livestock owners, while contracting of private veterinarians was not officially required. Six years later, due to increase in human outbreaks associated with livestock handling, there is a need to find out the risk factors of livestock anthrax in Georgia. OBJECTIVE: To identify exposures and risk factors associated with livestock anthrax. METHODS: A matched case-control study design was used to recruit the owners of individual livestock anthrax cases that occurred between June 2013 and May 2015, and owners of unaffected livestock from within ("village control") and outside the village ("area control"). We collected data about the case and control livestock animals' exposure and risk factors within the one-month prior to the disease onset of the case livestock (or matched case for the controls). We used logistic regression analysis (univariate and multivariable) to calculate the odds ratios of exposures and risk factors. RESULTS: During the study period, 36 anthrax cases met the case definition and were enrolled in the study; 67 matched village control livestock and 71 matched area control livestock were also enrolled. The findings from multivariable logistic regression analysis demonstrate that vaccination within the last two years significantly reduced the odds of anthrax in cattle (OR = 0.014; 95% Confidence interval = <0.001, 0.99). The other factors that were significantly protective against anthrax were 'animals being in covered fence area/barn' (OR = 0.065; p-value = 0.036), and 'female animal being pregnant or milking compared to heifer' (OR = 0.006; p-value = 0.037). CONCLUSIONS: The information obtained from this study has involved and been presented to decision makers, used to build technical capacity of veterinary staff, and to foster a One Health approach to the control of zoonotic diseases which will optimize prevention and control strategies. Georgia has embedded the knowledge and specific evidence that vaccination is a highly protective measure to prevent anthrax deaths among livestock, to which primary emphasis of the anthrax control program will be given. Education of livestock keepers in Georgia is an overriding priority.

Development and Performance of a Checklist for Initial Triage After an Anthrax Mass Exposure Event.

Background: Population exposure to Bacillus anthracis spores could cause mass casualties requiring complex medical care. Rapid identification of patients needing anthrax-specific therapies will improve patient outcomes and resource use. Objective: To develop a checklist that rapidly distinguishes most anthrax from nonanthrax illnesses on the basis of clinical presentation and identifies patients requiring diagnostic testing after a population exposure. Design: Comparison of published anthrax case reports from 1880 through 2013 that included patients seeking anthrax-related care at 2 epicenters of the 2001 U.S. anthrax attacks. Setting: Outpatient and inpatient. Patients: 408 case patients with inhalation, ingestion, and cutaneous anthrax and primary anthrax meningitis, and 657 control patients. Measurements: Diagnostic test characteristics, including positive and negative likelihood ratios (LRs) and patient triage assignation. Results: Checklist-directed triage without diagnostic testing correctly classified 95% (95% CI, 93% to 97%) of 353 adult anthrax case patients and 76% (CI, 73% to 79%) of 647 control patients (positive LR, 3.96 [CI, 3.45 to 4.55]; negative LR, 0.07 [CI, 0.04 to 0.11]; false-negative rate, 5%; false-positive rate, 24%). Diagnostic testing was needed for triage in up to 5% of case patients and 15% of control patients and improved overall test characteristics (positive LR, 8.90 [CI, 7.05 to 11.24]; negative LR, 0.06 [CI, 0.04 to 0.09]; false-negative rate, 5%; false-positive rate, 11%). Checklist sensitivity and specificity were minimally affected by inclusion of pediatric patients. Sensitivity increased to 97% (CI, 94% to 100%) and 98% (CI, 96% to 100%), respectively, when only inhalation anthrax cases or higher-quality case reports were investigated. Limitations: Data on case patients were limited to nonstandardized, published observational reports, many of which lacked complete data on symptoms and signs of interest. Reporting bias favoring more severe cases and lack of intercurrent outbreaks (such as influenza) in the control populations may have improved test characteristics. Conclusion: A brief checklist covering symptoms and signs can distinguish anthrax from other conditions with minimal need for diagnostic testing after known or suspected population exposure. Primary Funding Source: U.S. Department of Health and Human Services.

Enhancing Surveillance and Diagnostics in Anthrax-Endemic Countries.

Naturally occurring anthrax disproportionately affects the health and economic welfare of poor, rural communities in anthrax-endemic countries. However, many of these countries have limited anthrax prevention and control programs. Effective prevention of anthrax outbreaks among humans is accomplished through routine livestock vaccination programs and prompt response to animal outbreaks. The Centers for Disease Control and Prevention uses a 2-phase framework when providing technical assistance to partners in anthrax-endemic countries. The first phase assesses and identifies areas for improvement in existing human and animal surveillance, laboratory diagnostics, and outbreak response. The second phase provides steps to implement improvements to these areas. We describe examples of implementing this framework in anthrax-endemic countries. These activities are at varying stages of completion; however, the public health impact of these initiatives has been encouraging. The anthrax framework can be extended to other zoonotic diseases to build on these efforts, improve human and animal health, and enhance global health security.

Modeling the environmental suitability of anthrax in Ghana and estimating populations at risk: Implications for vaccination and control.

Anthrax is hyper-endemic in West Africa. Despite the effectiveness of livestock vaccines in controlling anthrax, underreporting, logistics, and limited resources makes implementing vaccination campaigns difficult. To better understand the geographic limits of anthrax, elucidate environmental factors related to its occurrence, and identify human and livestock populations at risk, we developed predictive models of the environmental suitability of anthrax in Ghana. We obtained data on the location and date of livestock anthrax from veterinary and outbreak response records in Ghana during 2005-2016, as well as livestock vaccination registers and population estimates of characteristically high-risk groups. To predict the environmental suitability of anthrax, we used an ensemble of random forest (RF) models built using a combination of climatic and environmental factors. From 2005 through the first six months of 2016, there were 67 anthrax outbreaks (851 cases) in livestock; outbreaks showed a seasonal peak during February through April and primarily involved cattle. There was a median of 19,709 vaccine doses [range: 0-175 thousand] administered annually. Results from the RF model suggest a marked ecological divide separating the broad areas of environmental suitability in northern Ghana from the southern part of the country. Increasing alkaline soil pH was associated with a higher probability of anthrax occurrence. We estimated 2.2 (95% CI: 2.0, 2.5) million livestock and 805 (95% CI: 519, 890) thousand low income rural livestock keepers were located in anthrax risk areas. Based on our estimates, the current anthrax vaccination efforts in Ghana cover a fraction of the livestock potentially at risk, thus control efforts should be focused on improving vaccine coverage among high risk groups.

Postexposure Prophylaxis After Possible Anthrax Exposure: Adherence and Adverse Events.

Anthrax postexposure prophylaxis (PEP) was recommended to 42 people after a laboratory incident that involved potential aerosolization of Bacillus anthracis spores in 2 laboratories at the Centers for Disease Control and Prevention in 2014. At least 31 (74%) individuals who initiated PEP did not complete either the recommended 60 days of antimicrobial therapy or the 3-dose vaccine regimen. Among the 29 that discontinued the antimicrobial component of PEP, most (38%) individuals discontinued PEP because of their low perceived risk of infection; 9 (31%) individuals discontinued prophylaxis due to PEP-related minor adverse events, and 10% cited both low risk and adverse events as their reason for discontinuation. Most minor adverse events reported were gastrointestinal complaints, and none required medical attention. Individuals taking ciprofloxacin were twice as likely (RR = 2.02, 95% CI = 1.1-3.6) to discontinue antimicrobial prophylaxis when compared to those taking doxycycline. In the event anthrax PEP is recommended, public health messages and patient education materials will need to address potential misconceptions regarding exposure risk and provide information about possible adverse events in order to promote PEP adherence.

A Case-Study of Implementation of Improved Strategies for Prevention of Laboratory-acquired Brucellosis.

BACKGROUND: In 2012, the Alaska Section of Epidemiology investigated personnel potentially exposed to a Brucella suis isolate as it transited through three laboratories. METHODS: We summarize the first implementation of the United States Centers for Disease Control and Prevention 2013 revised recommendations for monitoring such exposures: (1) risk classification; (2) antimicrobial postexposure prophylaxis; (3) serologic monitoring; and (4) symptom surveillance. RESULTS: Over 30 people were assessed for exposure and subsequently monitored for development of illness. No cases of laboratory-associated brucellosis occurred. Changes were made to gaps in laboratory biosafety practices that had been identified in the investigation. CONCLUSION: Achieving full compliance for the precise schedule of serologic monitoring was challenging and resource intensive for the laboratory performing testing. More refined exposure assessments could inform decision making for follow-up to maximize likelihood of detecting persons at risk while not overtaxing resources.