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 community perceptions and risk to common zoonotic diseases among communities living at the human-livestock-wildlife interface in Nakuru West, Kenya: A participatory epidemiology approach.

BACKGROUND: Zoonoses account for most of the emerging and re-emerging infections in Kenya and in other low to medium-income countries across the world. The human-livestock-wildlife interface provides a nexus where transmission and spread of these zoonotic diseases could occur among communities farming in these areas. We sought to identify perceptions of the community living near the Lake Nakuru National Park in Kenya. METHODS: We used participatory epidemiology techniques (PE) involving Focus Group Discussion (FGD) among community members and Key Informant Interviews (KII) with the health, veterinary, and administration officers in July 2020. We used listing, pairwise matching, and proportional piling techniques during the FGDs in the randomly selected villages in the study area from a list of villages provided by the area government officers. Kruskal-Wallis test was used to compare the median scores between the zoonotic diseases, source of information, and response to disease occurrence. Medians with a z-score greater than 1.96 at 95% Confidence Level were considered to be significant. Content analysis was used to rank qualitative variables. RESULTS: We conducted seven FGDs and four KIIs. A total of 89 participants took part in the FGDs with their ages ranging from 26 to 85 years. Common zoonotic diseases identified by participants included anthrax, rabies, and brucellosis. Anthrax was considered to have the greatest impact by the participants (median = 4, z>1.96), while 4/7 (57%) of the FGDs identified consumption of uninspected meat as a way that people can get infected with zoonotic diseases. Community Health Volunteers (Median = 28, z = 2.13) and the government veterinary officer (median = 7, z = 1.8) were the preferred sources of information during disease outbreaks. CONCLUSION: The participants knew the zoonotic diseases common in the area and how the diseases can be acquired. We recommend increased involvement of the community in epidemio-surveillance of zoonotic diseases at the human-wildlife-livestock interface.

Assessment of socio-behavioural correlates and risk perceptions regarding anthrax disease in tribal communities of Odisha, Eastern India.

BACKGROUND: This study is a baseline survey to assess the knowledge, attitude and practices with regards to the anthrax disease among the communities before demonstrating a One Health approach for elimination of human anthrax in an endemic district of Odisha. A total of 2670 respondents from 112 villages of 14 blocks were interviewed for the study using a structured questionnaire by multi-stage sampling method. Descriptive statistics were reported and logistic regression was performed to estimate the relationship between the variables and knowledge of anthrax. RESULT: Out of 2670 participants in the study, 76.25% were male and about half were illiterate. Most of the respondents (54.19%) were involved in agriculture as an occupation. 71% of the respondents had livestock in their houses and farming was the main purpose for keeping the livestock. Only one-fifth of the respondents (20.26%) knew about anthrax and a majority of them have come across the disease during community outbreaks. Almost 25.9% of livestock owners had knowledge about vaccination against anthrax disease although 83.4% of the livestock owners disposed the animal carcass by burial method. CONCLUSION: The study findings indicated that the community members had poor knowledge of cause, symptoms, transmission and prevention of anthrax disease which may be improved by a One Health approach.

'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.

Assessment of knowledge, attitudes and practices towards anthrax in Narok County, Southern Kenya.

INTRODUCTION: anthrax is endemic in some parts of Kenya causing mortalities in livestock and morbidity in humans. On January 20th, 2018, news media reported suspected anthrax in a remote southern Kenyan village after villagers became ill following consumption of meat from a dead cow that was confirmed, by microscopy, to have died of anthrax. We assessed community knowledge, attitude and practices (KAP) to identify intervention gaps for anthrax prevention. METHODS: we conducted a KAP survey in randomly selected households (HHs) in villages from selected wards. Using multi-stage sampling approach, we administered structured questionnaire to persons aged ≥15 years to collect KAP information from February 11th-21st, 2018. From a set of questions for KAP, we scored participants' response as "1" for a correct response and "0" for an incorrect response. Univariate analysis and Chi-square tests were performed to explore determinants of KAP. Concurrently, we gathered qualitative data using interview guides for thematic areas on anthrax KAP from key informant interviews and focus group discussions. Qualitative data were transcribed in Ms Word and analyzed along themes by content analysis. RESULTS: among 334 respondents: 187/334 (56%) were male; mean age, 40.7±13.6 years; 331/334 (99.1%) had heard of anthrax and 304/331 (91.8%) knew anthrax to be zoonotic. Transmission was considered to be through eating dead-carcasses by 273/331 (82.5%) and through contact with infected tissue by 213/331 (64.4%). About 59% (194/329) regularly vaccinated their livestock against anthrax, 53.0% (174/328) had slaughtered or skinned a dead-animal and 59.5% (195/328) practiced home slaughter while 52.9% (172/325) treated sick-animals by themselves. Sex (p≤0.001), age (p=0.007) and livestock-rearing years (p≤0.001) were significantly associated with knowledge and practice. CONCLUSION: there were differences in knowledge and practices towards anthrax by age-group and sex. Enhanced public health education and targeted interventions by relevant government agencies is recommended.

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.

Medical Spending for the 2001 Anthrax Letter Attacks.

ABSTRACTIntroductionThis paper assesses the total medical costs associated with the US anthrax letter attacks of 2001. This information can be used to inform policies, which may help mitigate the potential economic impacts of similar bioterrorist attacks. METHODS: Journal publications and news reports were reviewed to establish the number of people who were exposed, were potentially exposed, received prophylactics, and became ill. Where available, cost data from the anthrax letter attacks were used. Where data were unavailable, high, low, and best cost estimates were developed from the broader literature to create a cost model and establish economic impacts. RESULTS: Medical spending totaled approximately $177 million. CONCLUSIONS: The largest expenditures stemmed from self-initiated prophylaxis (worried well): people who sought prophylactic treatment without any indication that they had been exposed to anthrax letters. This highlights an area of focus for mitigating the economic impacts of future disasters. (Disaster Med Public Health Preparedness. 2019;13:539-546).

Recalibration of the Grunow-Finke Assessment Tool to Improve Performance in Detecting Unnatural Epidemics.

Successful identification of unnatural epidemics relies on a sensitive risk assessment tool designed for the differentiation between unnatural and natural epidemics. The Grunow-Finke tool (GFT), which has been the most widely used, however, has low sensitivity in such differentiation. We aimed to recalibrate the GFT and improve the performance in detection of unnatural epidemics. The comparator was the original GFT and its application in 11 historical outbreaks, including eight confirmed unnatural outbreaks and three natural outbreaks. Three steps were involved: (i) removing criteria, (ii) changing weighting factors, and (iii) adding and refining criteria. We created a series of alternative models to examine the changes on the parameter likelihood of unnatural outbreaks until we found a model that correctly identified all the unnatural outbreaks and natural ones. Finally, the recalibrated GFT was tested and validated with data from an unnatural and natural outbreak, respectively. A total of 238 models were tested. Through the removal of criteria, increasing or decreasing weighting factors of other criteria, adding a new criterion titled "special insights," and setting a new threshold for likelihood, we increased the sensitivity of the GFT from 38% to 100%, and retained the specificity at 100% in detecting unnatural epidemics. Using test data from an unnatural and a natural outbreak, the recalibrated GFT correctly classified their etiology. The recalibrated GFT could be integrated into routine outbreak investigation by public health institutions and agencies responsible for biosecurity.

Best practice assessment of disease modelling for infectious disease outbreaks.

During emerging disease outbreaks, public health, emergency management officials and decision-makers increasingly rely on epidemiological models to forecast outbreak progression and determine the best response to health crisis needs. Outbreak response strategies derived from such modelling may include pharmaceutical distribution, immunisation campaigns, social distancing, prophylactic pharmaceuticals, medical care, bed surge, security and other requirements. Infectious disease modelling estimates are unavoidably subject to multiple interpretations, and full understanding of a model's limitations may be lost when provided from the disease modeller to public health practitioner to government policymaker. We review epidemiological models created for diseases which are of greatest concern for public health protection. Such diseases, whether transmitted from person-to-person (Ebola, influenza, smallpox), via direct exposure (anthrax), or food and waterborne exposure (cholera, typhoid) may cause severe illness and death in a large population. We examine disease-specific models to determine best practices characterising infectious disease outbreaks and facilitating emergency response and implementation of public health policy and disease control measures.

Changing livestock vaccination policy alters the epidemiology of human anthrax, Georgia, 2000-2013.

Anthrax is a widely spread zoonotic disease found on nearly every continent. To control the disease in humans and animals, annual livestock vaccination is recommended. However, in 2007, the country of Georgia ended its policy of compulsory annual livestock anthrax vaccination. Our objective was to assess how the epidemiology of human anthrax has evolved from 2000-2013 in Georgia, in the wake of this cessation. We used passive surveillance data on epidemiological surveys of human anthrax case patients. Risk factors and rates of self-reported sources of infection were compared, before and after the change in livestock vaccination policy. We mapped ethnicity-adjusted incidence during the two periods and assessed changes in the spatial pattern of risk. The overall risk of human anthrax increased >5-fold, from 0.7 cases per 100,000 in 2000 to 3.7 cases per 100,000 by 2013. Ethnic disparities in risk became pronounced; from 2000 to 2013, incidence increased >60-fold in Azerbaijanis from 0.35 to 21.1 cases/100,000 Azerbaijanis compared to 0.61 to 1.9 cases/100,000 among ethnic Georgians. Food-borne exposures from purchasing meat increased from 11% in 2000-2006 to 21% in 2007-2013. Spatial analyses revealed a shift from a random pattern of reporting pre-policy change to clustering among district municipalities following the change in policy. Our findings indicate there were unintended human health consequences associated with changing livestock vaccination policy. Following a reduction in the immunizations administered, there was a major shift in the epidemiology of human anthrax in Georgia. Current infection risk is now highest among ethnic minorities. Increased reporting among individuals uncharacteristically at risk for anthrax from foodborne exposures suggests spillover from modes of agricultural production. Given the importance of human-livestock health linkages, careful evaluations of policy need to be undertaken before changes to animal vaccination are made.

Low-Cost National Media-Based Surveillance System for Public Health Events, Bangladesh.

We assessed a media-based public health surveillance system in Bangladesh during 2010-2011. The system is a highly effective, low-cost, locally appropriate, and sustainable outbreak detection tool that could be used in other low-income, resource-poor settings to meet the capacity for surveillance outlined in the International Health Regulations 2005.

Use of Multicriteria Risk Ranking of Zoonotic Diseases in a Developing Country: Case Study of Mongolia.

Many developing countries face significant health burdens associated with a high incidence of endemic zoonoses and difficulties in integrated control measures for both the human and animal populations. The objective of this study was to develop and apply a multicriteria ranking model for zoonoses in Mongolia, a country highly affected by zoonotic disease, to inform optimal resource allocation at the national level. Diseases were evaluated based on their impact on human health, livestock sector health and the wider society through affects on the economic value of livestock, as well as the feasibility of control in both the human and livestock population. Data on disease in Mongolia were collected from various government departments including the Mongolian State Central Laboratory, the Mongolian Department of Veterinary and Animal Breeding, the Mongolian Ministry of Health, Mongolian National Center for Communicable Diseases, the National Center for Zoonotic Disease and expert opinion from a workshop with a number of Mongolian Government officials and researchers. A combined score for both impact of the disease and feasibility of its control was calculated. Five zoonotic diseases were determined to be of high priority from this assessment (i.e. ovine brucellosis, echinococcosis (hydatids), rabies, anthrax and bovine brucellosis). The results supported some of the findings for high-priority diseases (namely brucellosis, rabies and anthrax) from a previous priority setting exercise carried out in Mongolia in 2011, but also identified and ranked additional animal diseases of public health importance. While the process of model development was largely Mongolian specific, the experience of developing and parameterizing this multicriteria ranking model could be replicated by other countries where zoonoses have substantive impacts on both animal and human health.

Clinical Framework and Medical Countermeasure Use During an Anthrax Mass-Casualty Incident.

In 2014, CDC published updated guidelines for the prevention and treatment of anthrax (Hendricks KA, Wright ME, Shadomy SV, et al. Centers for Disease Control and Prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis 2014;20[2]. Available at http://wwwnc.cdc.gov/eid/article/20/2/13-0687_article.htm). These guidelines provided recommended best practices for the diagnosis and treatment of persons with naturally occurring or bioterrorism-related anthrax in conventional medical settings. An aerosolized release of Bacillus anthracis spores over densely populated areas could become a mass-casualty incident. To prepare for this possibility, the U.S. government has stockpiled equipment and therapeutics (known as medical countermeasures [MCMs]) for anthrax prevention and treatment. However, previously developed, publicly available clinical recommendations have not addressed the use of MCMs or clinical management during an anthrax mass-casualty incident, when the number of patients is likely to exceed the ability of the health care infrastructure to provide conventional standards of care and supplies of MCMs might be inadequate to meet the demand required. To address this gap, in 2013, CDC conducted a series of systematic reviews of the scientific literature on anthrax to identify evidence that could help clinicians and public health authorities set guidelines for intravenous antimicrobial and antitoxin use, diagnosis of anthrax meningitis, and management of common anthrax-specific complications in the setting of a mass-casualty incident. Evidence from these reviews was presented to professionals with expertise in anthrax, critical care, and disaster medicine during a series of workgroup meetings that were held from August 2013 through March 2014. In March 2014, a meeting was held at which 102 subject matter experts discussed the evidence and adapted the existing best practices guidance to a clinical use framework for the judicious, efficient, and rational use of stockpiled MCMs for the treatment of anthrax during a mass-casualty incident, which is described in this report. This report addresses elements of hospital-based acute care, specifically antitoxins and intravenous antimicrobial use, and the diagnosis and management of common anthrax-specific complications during a mass-casualty incident. The recommendations in this report should be implemented only after predefined triggers have been met for shifting from conventional to contingency or crisis standards of care, such as when the magnitude of cases might lead to impending shortages of intravenous antimicrobials, antitoxins, critical care resources (e.g., chest tubes and chest drainage systems), or diagnostic capability. This guidance does not address primary triage decisions, anthrax postexposure prophylaxis, hospital bed or workforce surge capacity, or the logistics of dispensing MCMs. Clinicians, hospital administrators, state and local health officials, and planners can use these recommendations to assist in the development of crisis protocols that will ensure national preparedness for an anthrax mass-casualty incident.

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.