Central Nervous System Antimicrobial Exposure and Proposed Dosing for Anthrax Meningitis.

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 ß-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.

Anthrax in one health in Southern and Southeastern Europe - the effect of climate change?

Anthrax is a serious infection caused by Bacillus anthracis. The anthracis spores are highly resistant and can persist in the environment for several decades. Therefore, anthrax is considered a global health threat affecting wildlife, livestock, and the general public. The resistance mechanism is influenced not only by the environment or the ecological niche but also by virulence factors. In the last 10 years the Southern and Southeastern Europe have been confronted with this threat. Recently, there have been 8 human anthrax cases reported in Croatia (2022), and 4 cases in Romania (2023). Moreover, this incident and the COVID situation could be a starting point to encourage researchers to raise the alarm. On the other hand, climate change is causing glaciers to melt and land to thaw, and many wetlands and swampy areas are being drained. It should not be forgotten that epidemiological and epizootic threats significantly affect the country's economic development. The Covid-19 epidemic best illustrates these threats.

Assessment of calcium hypochlorite for Bacillus anthracis spore surface's decontamination.

Contamination with microorganisms occurs in laboratories but is also of high concern in the context of bioterrorism. Decontamination is a cornerstone that promotes good laboratory practices and occupational health and safety. Among the most resistant structures formed by microorganisms are spores, produced notably by Clostridium and Bacillus species. Here, we compared six products containing four different molecules (hydrogen peroxide, peracetic acid, sodium and calcium hypochlorite) on B. anthracis Sterne spores. We first selected the most efficient product based on its activity against spore suspensions using French and European standards. Four products showed sporicidal activity, of which only two did so in a time frame consistent with good laboratory practices. Then, we tested one of these two products under laboratory conditions on fully virulent B. anthracis spores, during common use and after contamination through a spill of a highly concentrated spore suspension. We, thus, robustly validated a decontaminant based on calcium hypochlorite not only on its ability to kill spores but also on its effectiveness under laboratory conditions. At the end, we were able to assure a complete disinfection in 1 min after spillover and in 2 min for common use.

'We dry contaminated meat to make it safe': An assessment of knowledge, attitude and practices on anthrax during an outbreak, Kisumu, Kenya, 2019.

INTRODUCTION: Anthrax is the highest-ranked priority zoonotic disease in Kenya with about ten human cases annually. Anthrax outbreak was reported in Kisumu East Sub County after some villagers slaughtered and ate beef from a cow suspected to have died of anthrax. We aimed at establishing the magnitude of the outbreak, described associated factors, and assessed community knowledge, attitude, and practices on anthrax. METHODS: We reviewed human and animal records, conducted case search and contact tracing using standard case definitions in the period from July 1through to July 28, 2019. A cross-sectional study was conducted to assess community knowledge, attitude, and practices towards anthrax. The household selection was done using multistage sampling. We cleaned and analyzed data in Ms. Excel and Epi Info. Descriptive statistics were carried out for continuous and categorical variables while analytical statistics for the association between dependent and independent variables were calculated. RESULTS: Out of 53 persons exposed through consumption or contact with suspicious beef, 23 cases (confirmed: 1, probable: 4, suspected: 18) were reviewed. The proportion of females was 52.17% (12/23), median age 13.5 years and range 45 years. The attack rate was 43.4% (23/53) and the case fatality rate was 4.35% (1/23). Knowledge level, determined by dividing those considered to be 'having good knowledge' on anthrax (numerator) by the total number of respondents (denominator) in the population regarding cause, transmission, symptoms and prevention was 51% for human anthrax and 52% for animal anthrax. Having good knowledge on anthrax was associated with rural residence [OR = 5.5 (95% CI 2.1-14.4; p<0.001)], having seen a case of anthrax [OR = 6.2 (95% CI 2.8-14.2; p<0.001)] and among those who present cattle for vaccination [OR = 2.6 (95% CI 1.2-5.6; p = 0.02)]. About 23.2% (26/112) would slaughter and sell beef to neighbors while 63.4% (71/112) would bury or burn the carcass. Nearly 93.8% (105/112) believed vaccination prevents anthrax. However, 5.4% (62/112) present livestock for vaccination. CONCLUSION: Most anthrax exposures were through meat consumption. Poor knowledge of the disease might hamper prevention and control efforts.

Efficacy assessment of a triple anthrax chimeric antigen as a vaccine candidate in guinea pigs: challenge test with Bacillus anthracis 17 JB strain spores.

CONTEXT: Bacillus anthracis secretes a tripartite toxin comprising protective antigen (PA), edema factor (EF), and lethal factor (LF). The human anthrax vaccine is mainly composed of the anthrax protective antigen (PA). Considerable efforts are being directed towards improving the efficacy of vaccines because the use of commercial anthrax vaccines (human/veterinary) is associated with several limitations. OBJECTIVE: In this study, a triple chimeric antigen referred to as ELP (gene accession no: MT590758) comprising highly immunogenic domains of PA, LF, and EF was designed, constructed, and assessed for the immunization capacity against anthrax in a guinea pig model. MATERIALS AND METHODS: Immunization was carried out considering antigen titration and immunization protocol. The immunoprotective efficacy of the ELP was evaluated in guinea pigs and compared with the potency of veterinary anthrax vaccine using a challenge test with B. anthracis 17JB strain spores. RESULTS: The results demonstrated that the ELP antigen induced strong humoral responses. The T-cell response of the ELP was found to be similar to PA, and showed that the ELP could protect 100%, 100%, 100%, 80% and 60% of the animals from 50, 70, 90, 100 and 120 times the minimum lethal dose (MLD, equal 5 × 105 spore/ml), respectively, which killed control animals within 48 h. DISCUSSION AND CONCLUSIONS: It is concluded that the ELP antigen has the necessary requirement for proper immunization against anthrax and it can be used to develop an effective recombinant vaccine candidate against anthrax.

The assessment of leading traits in the taxonomy of the Bacillus cereus group.

Bacillus cereus sensu lato strains (B. cereus group) are widely distributed in nature and have received interest for decades due to their importance in insect pest management, food production and their positive and negative repercussions in human health. Consideration of practical uses such as virulence, physiology, morphology, or ill-defined features have been applied to describe and classify species of the group. However, current comparative studies have exposed inconsistencies between evolutionary relatedness and biological significance among genomospecies of the B. cereus group. Here, the combined analyses of core-based phylogeny and all versus all Average Nucleotide Identity values based on 2116 strains were conducted to update the genomospecies circumscriptions within B. cereus group. These analyses suggested the existence of 57 genomospecies, 37 of which are novel, thus indicating that the taxonomic identities of more than 39% of the analyzed strains should be revised or updated. In addition, we found that whole-genome in silico analyses were suitable to differentiate genomospecies such as B. anthracis, B. cereus and B. thuringiensis. The prevalence of toxin and virulence factors coding genes in each of the genomospecies of the B. cereus group was also examined, using phylogeny-aware methods at wide-genome scale. Remarkably, Cry and emetic toxins, commonly assumed to be associated with B. thuringiensis and emetic B. paranthracis, respectively, did not show a positive correlation with those genomospecies. On the other hand, anthrax-like toxin and capsule-biosynthesis coding genes were positively correlated with B. anthracis genomospecies, despite not being present in all strains, and with presumably non-pathogenic genomospecies. Hence, despite these features have been so far considered relevant for industrial or medical classification of related species of the B. cereus group, they were inappropriate for their circumscription. In this study, genomospecies of the group were accurately affiliated and representative strains defined, generating a rational framework that will allow comparative analysis in epidemiological or ecological studies. Based on this classification the role of specific markers such as Type VII secretion system, cytolysin, bacillolysin, and siderophores such as petrobactin were pointed out for further analysis.

Risk mapping and eco-anthropogenic assessment of anthrax in the upper Zambezi basin.

In Zambia, anthrax has emerged as a serious disease decimating humans, livestock and wildlife with devastating effects on eco-tourism resulting in the destabilization of major pristine wildlife sanctuaries. Consequently, the thrust of this study was to establish the spatial distribution of anthrax and determine ecological drivers of its recurrence, maintenance and epidemiological linkage to anthropogenic activities. Environmental and biological samples were collected within the livestock production and conservation areas (n = 80). Each sample was serially tested for Bacillus anthracis positivity through blood agar culture and Gram stain technique, and then confirmation by multiplex polymerase chain reaction (MPCR). Questionnaires (n = 113) were conducted at independently distinct villages in terms of space and time. Most respondents showed that animals that died from anthrax were not properly disposed off. More likely than not, poverty being the main driver for anthrax carcass dressing and meat distribution contributed to environmental contamination with anthrax spores in areas where the animals subsequently died resulting in further environmental contamination, which is the major source of primary infection for livestock and wildlife. From the samples, 15 pure isolates of anthrax were obtained which were spatially distributed across four districts. Twelve, biologically plausible variables were found to be highly significant on multivariable logistic regression analysis model for questionnaires which included herd size (odds = 10.46; P = 0.005; CI 8.8-16), carcass disposal method (odds = 6.9; P = 0.001; CI = 3.4-9.8), access to veterinary services (odds = 10.87; P = 0.004; CI = 4.8-15.9) and management system (odds = 2.57; P = 0.001; CI = 1.3-7.5). In summary, the majority (78.7%) of anthrax outbreaks were observed in areas with low veterinary services (χ2  = 8.6162, P = 0.013) within the newly created districts of Nalolo, Mwandi and Luampa.

Fast and sensitive detection of an anthrax biomarker using SERS-based solenoid microfluidic sensor.

We report the application of a fully automated surface-enhanced Raman scattering (SERS)-based solenoid-embedded microfluidic device to the quantitative and sensitive detection of anthrax biomarker poly-γ-D-glutamic acid (PGA) in solution. Analysis is based on the competitive reaction between PGA and PGA-conjugated gold nanoparticles with anti-PGA-immobilized magnetic beads within a microfluidic environment. Magnetic immunocomplexes are trapped by yoke-type solenoids embedded within the device, and their SERS signals were directly measured and analyzed. To improve the accuracy of measurement process, external standard values for PGA-free serum were also measured through use of a control channel. This additional measurement greatly improves the reliability of the assay by minimizing the influence of extraneous experimental variables. The limit of detection (LOD) of PGA in serum, determined by our SERS-based microfluidic sensor, is estimated to be 100 pg/mL. We believe that the defined method represents a valuable analytical tool for the detection of anthrax-related aqueous samples.

Updating a B. anthracis Risk Model with Field Data from a Bioterrorism Incident.

In this study, a Bayesian framework was applied to update a model of pathogen fate and transport in the indoor environment. Distributions for model parameters (e.g., release quantity of B. anthracis spores, risk of illness, spore setting velocity, resuspension rate, sample recovery efficiency, etc.) were updated by comparing model predictions with measurements of B. anthracis spores made after one of the 2001 anthrax letter attacks. The updating process, which was implemented by using Markov chain Monte Carlo (MCMC) methods, significantly reduced the uncertainties of inputs with uniformed prior estimates: total quantity of spores released, the amount of spores exiting the room, and risk to occupants. In contrast, uncertainties were not greatly reduced for inputs for which informed prior data were available: deposition rates, resuspension rates, and sample recovery efficiencies. This suggests that prior estimates of these quantities that were obtained from a review of the technical literature are consistent with the observed behavior of spores in an actual attack. Posterior estimates of mortality risk for people in the room, when the spores were released, are on the order of 0.01 to 0.1, which supports the decision to administer prophylactic antibiotics. Multivariate sensitivity analyses were conducted to assess how effective different measurements were at reducing uncertainty in the estimated risk for the prior scenario. This analysis revealed that if the size distribution of the released particulates is known, then environmental sampling can be limited to accurately characterizing floor concentrations; otherwise, samples from multiple locations, as well as particulate and building air circulation parameters, need to be measured.

A One Health, participatory epidemiology assessment of anthrax (Bacillus anthracis) management in Western Uganda.

Sporadic anthrax outbreaks have occurred in and around Uganda's Queen Elizabeth National Park (QENP) for years, affecting wildlife, domestic animals, and humans. Reported outbreaks (2004-2005 and 2010) in QENP collectively killed over 500 wild animals and over 400 domestic animals. A 2011 outbreak in Sheema district temporarily froze local markets while killing two humans and seven bovines. One Health is multidisciplinary at its core, yet studies sometimes focus on the effects of animals on human health to the detriment of investigating the surrounding ecological and cultural contexts. Participatory methods connect problems - such as disease - to their context. A multidisciplinary team used participatory epidemiology and conventional structured questionnaires to investigate the impacts of anthrax on human livelihoods and the related perceptions of conservation, public health, and veterinary health efforts in the QENP area. Proximities to previous anthrax outbreaks and to QENP were treated as risk factors in the collection and evaluation of data. Participants' feedback indicates that anthrax prevalence may be greater than officially reported. Community member perceptions about anthrax and other diseases appear to be more closely related to their proximity to QENP than their proximity to anthrax outbreaks. Neither risk factor had a strong effect on knowledge of disease, nor any effect on behaviors associated with disease response or control. Instead, participants reported that social pressures, the economics of poverty, and the lack of health and veterinary infrastructure highly influenced responses to disease. The complex connections between the social needs and the economic context of these communities seem to be undermining current anthrax control and education measures. This livelihood-based decision-making may be unlikely to respond to educational intervention alone. This study provides a strong base for further research and for improvements in effective disease control.

Responding to biological incidents--what are the current issues in remediation of the contaminated environment?

Since 2000 there have been a number of biological incidents resulting in environmental contamination with Bacillus anthracis, the causative agent of anthrax. These incidents include the US anthrax attacks in 2001, the US and UK drumming incidents in 2006-2008 and more recently, anthrax contamination of heroin in 2009/2010 and 2012/2013. Remediation techniques used to return environments to normal have varied between incidents, with different decontamination technologies being employed. Many factors need to be considered before a remediation strategy or recovery option can be implemented, including; cost, time (length of application), public perception of risk, and sampling strategies (and results) to name a few. These incidents have demonstrated that consolidated guidance for remediating biologically contaminated environments in the aftermath of a biological incident was required. The UK Recovery Handbook for Biological Incidents (UKRHBI) is a project led by Public Health England (PHE), formerly the Health Protection Agency (HPA) to provide guidance and advice on how to remediate the environment following a biological incident or outbreak of infection, and is expected to be published in 2015.

Development of a simple and rapid method for the specific identification of organism causing anthrax by slide latex agglutination.

UNLABELLED: A specific latex agglutination test (LAT) based on anti-PA (protective antigen) antibodies having detection limit of 5 × 10(4) formalin treated Bacillus anthracis cells or 110 ng of PA was optimized in this study. The optimized LAT could detect anthrax toxin in whole blood as well as in serum from the animal models of anthrax infection. The protocol is a simple and promising method for the specific detection of bacteria causing anthrax under routine laboratory, as well as in field, conditions without any special equipments or expertise. SIGNIFICANCE AND IMPACT OF THE STUDY: The article presents the first report of a latex agglutination test for the specific identification of the cultures of bacteria causing anthrax. As the test is targeting one of anthrax toxic protein (PA), this can also be used to determine virulence of suspected organisms. At the same time, the same LAT can be used directly on whole blood or sera samples under field conditions for the specific diagnosis of anthrax.

Hollow-fiber pharmacodynamic studies and mathematical modeling to predict the efficacy of amoxicillin for anthrax postexposure prophylaxis in pregnant women and children.

Amoxicillin is considered an option for postexposure prophylaxis of Bacillus anthracis in pregnant and postpartum women who are breastfeeding and in children because of the potential toxicities of ciprofloxacin and doxycycline to the fetus and child. The amoxicillin regimen that effectively kills B. anthracis and prevents resistance is unknown. Fourteen-day dose range and dose fractionation studies were conducted in in vitro pharmacodynamic models to identify the exposure intensity and pharmacodynamic index of amoxicillin that are linked with optimized killing of B. anthracis and resistance prevention. Studies with dicloxacillin, a drug resistant to B. anthracis beta-lactamase, evaluated the role of beta-lactamase production in the pharmacodynamic indices for B. anthracis killing and resistance prevention. Dose fractionation studies showed that trough/MIC and not time above MIC was the index for amoxicillin that was linked to successful outcome through resistance prevention. Failure of amoxicillin regimens was due to inducible or stable high level expression of beta-lactamases. Studies with dicloxacillin demonstrated that a time above MIC of ≥94% was linked with treatment success when B. anthracis beta-lactamase activity was negated. Recursive partitioning analysis showed that amoxicillin regimens that produced peak concentrations of <10.99 µg/ml and troughs of >1.75 µg/ml provided a 100% success rate. Other amoxicillin peak and trough values produced success rates of 28 to 67%. For postpartum and pregnant women and children, Monte Carlo simulations predicted success rates for amoxicillin at 1 g every 8 h (q8h) of 53, 33, and 44% (30 mg/kg q8h), respectively. We conclude that amoxicillin is suboptimal for postexposure prophylaxis of B. anthracis in pregnant and postpartum women and in children.

Rapid identification of Bacillus anthracis spores in suspicious powder samples by using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS).

Rapid and reliable identification of Bacillus anthracis spores in suspicious powders is important to mitigate the safety risks and economic burdens associated with such incidents. The aim of this study was to develop and validate a rapid and reliable laboratory-based matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis method for identifying B. anthracis spores in suspicious powder samples. A reference library containing 22 different Bacillus sp. strains or hoax materials was constructed and coupled with a novel classification algorithm and standardized processing protocol for various powder samples. The method's limit of B. anthracis detection was determined to be 2.5 × 10(6) spores, equivalent to a 55-µg sample size of the crudest B. anthracis-containing powder discovered during the 2001 Amerithrax incidents. The end-to-end analysis method was able to successfully discriminate among samples containing B. anthracis spores, closely related Bacillus sp. spores, and commonly encountered hoax materials. No false-positive or -negative classifications of B. anthracis spores were observed, even when the analysis method was challenged with a wide range of other bacterial agents. The robustness of the method was demonstrated by analyzing samples (i) at an external facility using a different MALDI-TOF MS instrument, (ii) using an untrained operator, and (iii) using mixtures of Bacillus sp. spores and hoax materials. Taken together, the observed performance of the analysis method developed demonstrates its potential applicability as a rapid, specific, sensitive, robust, and cost-effective laboratory-based analysis tool for resolving incidents involving suspicious powders in less than 30 min.

Immuno capture PCR for rapid and sensitive identification of pathogenic Bacillus anthracis.

Immuno capture PCR (IPCR) is a technique capable of detecting the pathogens with high specificity and sensitivity. Rapid and accurate detection of Bacillus anthracis was achieved using anti-EA1 antibodies to capture the cells and two primer sets targeting the virulence factors of the pathogen i.e., protective antigen (pag) and capsule (cap) in an IPCR format. Monoclonal antibodies specific to B. anthracis were generated against extractable antigen 1 protein and used as capture antibody onto 96 well polystyrene plates. Following the binding of the pathogen, the DNA extraction was carried out in the well itself and further processed for PCR assay. We compared IPCR described here with conventional duplex PCR using the same primers and sandwich ELISA using the monoclonal antibodies developed in the present study. IPCR was capable of detecting as few as 10 and 100 cfu ml⁻¹ of bacterial cells and spores, respectively. IPCR was found to be 2-3 logs more sensitive than conventional duplex PCR and the sandwich ELISA. The effect of other bacteria and any organic materials on IPCR was also analyzed and found that this method was robust with little change in the sensitivity in the presence of interfering agents. Moreover, we could demonstrate a simple process of microwave treatment for spore disruption which otherwise are resistant to chemical treatments. Also, the IPCR could clearly distinguish the pathogenic and nonpathogenic strains of B. anthracis in the same assay. This can help in saving resources on unnecessary decontamination procedures during false alarms.

Assessment of delivery parameters with the multi-electrode array for development of a DNA vaccine against Bacillus anthracis.

Gene electrotransfer (GET) enhances delivery of DNA vaccines by increasing both gene expression and immune responses. Our lab has developed the multi-electrode array (MEA) for DNA delivery to skin. The MEA was used at constant pulse duration (150 ms) and frequency (6.67 Hz). In this study, delivery parameters including applied voltage (5-45 V), amount of plasmid (100-300 µg), and number of treatments (2-3) were evaluated for delivery of a DNA vaccine. Mice were intradermally injected with plasmid expressing Bacillus anthracis protective antigen with or without GET and αPA serum titers measured. Within this experiment no significant differences were noted in antibody levels from varying dose or treatment number. However, significant differences were measured from applied voltages of 25 and 35 V. These voltages generated antibody levels between 20,000 and 25,000. Serum from animals vaccinated with these conditions also resulted in toxin neutralization in 40-60% of animals. Visual damage was noted at MEA conditions of 40 V. No damage was noted either visually or histologically from conditions of 35 V or below. These results reflect the importance of establishing appropriate electrical parameters and the potential for the MEA in non-invasive DNA vaccination against B. anthracis.

Assessment of medical reserve corps volunteers' emergency response willingness using a threat- and efficacy-based model.

The goal of this study was to investigate the willingness of Medical Reserve Corps (MRC) volunteers to participate in public health emergency-related activities by assessing their attitudes and beliefs. MRC volunteers responded to an online survey organized around the Extended Parallel Process Model (EPPM). Respondents reported agreement with attitude/belief statements representing perceived threat, perceived efficacy, and personal/organizational preparedness in 4 scenarios: a weather-related disaster, a pandemic influenza emergency, a radiological ("dirty bomb") emergency, and an inhalational anthrax bioterrorism emergency. Logistic regression analyses were used to evaluate predictors of volunteer response willingness. In 2 response contexts (if asked and regardless of severity), self-reported willingness to respond was higher among those with a high perceived self-efficacy than among those with low perceived self-efficacy. Analyses of the association between attitude/belief statements and the EPPM profiles indicated that, under all 4 scenarios and with few exceptions, those with a perceived high threat/high efficacy EPPM profile had statistically higher odds of agreement with the attitude/belief statements than those with a perceived low threat/low efficacy EPPM profile. The radiological emergency consistently received the lowest agreement rates for the attitude/belief statements and response willingness across scenarios. The findings suggest that enrollment with an MRC unit is not automatically predictive of willingness to respond in these types of scenarios. While MRC volunteers' self-reported willingness to respond was found to differ across scenarios and among different attitude and belief statements, the identification of self-efficacy as the primary predictor of willingness to respond regardless of severity and if asked highlights the critical role of efficacy in an organized volunteer response context.

Quantitative assessment of anthrax vaccine immunogenicity using the dried blood spot matrix.

The collection, processing and transportation to a testing laboratory of large numbers of clinical samples during an emergency response situation present significant cost and logistical issues. Blood and serum are common clinical samples for diagnosis of disease. Serum preparation requires significant on-site equipment and facilities for immediate processing and cold storage, and significant costs for cold-chain transport to testing facilities. The dried blood spot (DBS) matrix offers an alternative to serum for rapid and efficient sample collection with fewer on-site equipment requirements and considerably lower storage and transport costs. We have developed and validated assay methods for using DBS in the quantitative anti-protective antigen IgG enzyme-linked immunosorbent assay (ELISA), one of the primary assays for assessing immunogenicity of anthrax vaccine and for confirmatory diagnosis of Bacillus anthracis infection in humans. We have also developed and validated high-throughput data analysis software to facilitate data handling for large clinical trials and emergency response.

Cost-effectiveness comparison of response strategies to a large-scale anthrax attack on the chicago metropolitan area: impact of timing and surge capacity.

Rapid public health response to a large-scale anthrax attack would reduce overall morbidity and mortality. However, there is uncertainty about the optimal cost-effective response strategy based on timing of intervention, public health resources, and critical care facilities. We conducted a decision analytic study to compare response strategies to a theoretical large-scale anthrax attack on the Chicago metropolitan area beginning either Day 2 or Day 5 after the attack. These strategies correspond to the policy options set forth by the Anthrax Modeling Working Group for population-wide responses to a large-scale anthrax attack: (1) postattack antibiotic prophylaxis, (2) postattack antibiotic prophylaxis and vaccination, (3) preattack vaccination with postattack antibiotic prophylaxis, and (4) preattack vaccination with postattack antibiotic prophylaxis and vaccination. Outcomes were measured in costs, lives saved, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). We estimated that postattack antibiotic prophylaxis of all 1,390,000 anthrax-exposed people beginning on Day 2 after attack would result in 205,835 infected victims, 35,049 fulminant victims, and 28,612 deaths. Only 6,437 (18.5%) of the fulminant victims could be saved with the existing critical care facilities in the Chicago metropolitan area. Mortality would increase to 69,136 if the response strategy began on Day 5. Including postattack vaccination with antibiotic prophylaxis of all exposed people reduces mortality and is cost-effective for both Day 2 (ICER=$182/QALY) and Day 5 (ICER=$1,088/QALY) response strategies. Increasing ICU bed availability significantly reduces mortality for all response strategies. We conclude that postattack antibiotic prophylaxis and vaccination of all exposed people is the optimal cost-effective response strategy for a large-scale anthrax attack. Our findings support the US government's plan to provide antibiotic prophylaxis and vaccination for all exposed people within 48 hours of the recognition of a large-scale anthrax attack. Future policies should consider expanding critical care capacity to allow for the rescue of more victims.