Risk factors and spatio-temporal patterns of livestock anthrax in Khuvsgul Province, Mongolia.

Anthrax is a worldwide zoonotic disease. Anthrax has long been a public health and socio-economic issue in Mongolia. Presently, there is no spatial information on carcass burial sites as a potential hazard of future anthrax outbreaks and possible risk factors associated with anthrax occurrences in Mongolia. Here, we analyze retrospective data (1986-2015) on the disposal sites of livestock carcasses to describe historical spatio-temporal patterns of livestock anthrax in Khuvsgul Province, which showed the highest anthrax incidence rate in Mongolia. From the results of spatial mean and standard deviational ellipse analyses, we found that the anthrax spatial distribution in livestock did not change over the study period, indicating a localized source of exposure. The multi-distance spatial cluster analysis showed that carcass sites distributed in the study area are clustered. Using kernel density estimation analysis on carcass sites, we identified two anthrax hotspots in low-lying areas around the south and north regions. Notably, this study disclosed a new hotspot in the northern part that emerged in the last decade of the 30-year study period. The highest proportion of cases was recorded in cattle, whose prevalence per area was highest in six districts (i.e., Murun, Chandmani-Undur, Khatgal, Ikh-Uul, Tosontsengel, and Tsagaan-Uul), suggesting that vaccination should prioritize cattle in these districts. Furthermore, size of outbreaks was influenced by the annual summer mean air temperature of Khuvsgul Province, probably by affecting the permafrost freeze-thawing activity.

Outbreak of gastrointestinal anthrax following eating beef of suspicious origin: Isingiro District, Uganda, 2017.

INTRODUCTION: Gastrointestinal anthrax is a rare but serious disease. In August 2017, Isingiro District, Uganda reported a cluster of >40 persons with acute-onset gastroenteritis. Symptoms included bloody diarrhoea. We investigated to identify the etiology and exposures, and to inform control measures. METHODS: We defined a suspected case as acute-onset of diarrhoea or vomiting during 15-31 August 2017 in a resident (aged≥2 years) of Kabingo sub-county, Isingiro District; a confirmed case was a suspected case with a clinical sample positive for Bacillus anthracis by culture or PCR. We conducted descriptive epidemiology to generate hypotheses. In a case-control study, we compared exposures between case-patients and neighbourhood-matched controls. We used conditional logistic regression to compute matched odds ratios (MOR) for associations of illness with exposures. RESULTS: We identified 61 cases (58 suspected and 3 confirmed; no deaths). In the case-control study, 82% of 50 case-patients and 12% of 100 controls ate beef purchased exclusively from butchery X during the week before illness onset (MOR = 46, 95%CI = 4.7-446); 8.0% of case-patients and 3.0% of controls ate beef purchased from butchery X and elsewhere (MOR = 19, 95%CI = 1.0-328), compared with 6.0% of case-patients and 30% of controls who did not eat beef. B. anthracis was identified in two vomitus and one stool sample. Butchery X slaughtered a sick cow and sold the beef during case-patients' incubation period. CONCLUSION: This gastrointestinal anthrax outbreak occurred due to eating beef from butchery X. We recommended health education, safe disposal of the carcasses of livestock or game animals, and anthrax vaccination for livestock.

An integrated experimental-computational approach for predicting virulence in New Zealand white rabbits and humans following inhalation exposure to Bacillus anthracis spores.

Inhalation of Bacillus anthracis spores can lead to an anthrax infection that can be fatal. Previously published mathematical models have extrapolated kinetic rates associated with bacterial growth in New Zealand White (NZW) rabbits to humans, but to date, actual measurements of the underlying processes associated with anthrax virulence between species have not been conducted. To address this knowledge gap, we have quantified species-specific rate constants associated with germination, proliferation, and immune cell inactivation of B. anthracis Sterne using an in vitro test platform that includes primary lung epithelial and immune cells. The generated data was then used to develop a physiologically based biokinetic model (PBBK) which quantitatively compares bacterial growth and mean time to death under lethal conditions in rabbits and humans. Simulations based upon our in vitro data and previously published in vivo data from rabbits indicate that disease progression is likely to be faster in humans than in NZW rabbits under comparable total deposited dose conditions. With the computational framework established, PBBK parameters can now be refined using experimental data for lethal B. anthracis strains (e.g. Ames) under identical conditions in future studies. The PBBK model can also be linked to existing aerosol dosimetry models that account for species-specific differences in aerosol deposition patterns to further improve the human health risk assessment of inhalation anthrax.

Modeling the macrophage-anthrax spore interaction: Implications for early host-pathogen interactions.

Inhalational anthrax, caused by the gram positive bacteria Bacillus anthracis, is a potentially fatal form of anthrax infection. It is initiated after inhaled spores are deposited in the lung, phagocytosed by immune cells, and subsequently transported to nearby lymph nodes. Intracellular spores that successfully germinate and become vegetative bacteria can lyse their host cell and contribute to bacterial outgrowth and toxin production. To better understand the early disease dynamics of the host-pathogen interaction, we develop a mathematical model of ordinary differential Equations and estimate parameters using available data. The model which consists of two subsystems is designed in accordance with an in vitro experimental protocol in which macrophages were challenged with varying doses of spores at spore-to-macrophage ratios of 1:1, 1:2, 1:10, 1:20. Initial modeling results suggested the need to consider two distinct subpopulations of anthrax bacteria: newly germinated bacteria which cannot replicate immediately and fully vegetative bacteria that can. Additional modeling results provide insights into possible reasons why macrophage-induced killing is more effective at the 1:20 ratio.

Efficacy Projection of Obiltoxaximab for Treatment of Inhalational Anthrax across a Range of Disease Severity.

Inhalational anthrax has high mortality even with antibiotic treatment, and antitoxins are now recommended as an adjunct to standard antimicrobial regimens. The efficacy of obiltoxaximab, a monoclonal antibody against anthrax protective antigen (PA), was examined in multiple studies conducted in two animal models of inhalational anthrax. A single intravenous bolus of 1 to 32 mg/kg of body weight obiltoxaximab or placebo was administered to New Zealand White rabbits (two studies) and cynomolgus macaques (4 studies) at disease onset (significant body temperature increase or detection of serum PA) following lethal challenge with aerosolized Bacillus anthracis spores. The primary endpoint was survival. The relationship between efficacy and disease severity, defined by pretreatment bacteremia and toxemia levels, was explored. In rabbits, single doses of 1 to 16 mg/kg obiltoxaximab led to 17 to 93% survival. In two studies, survival following 16 mg/kg obiltoxaximab was 93% and 62% compared to 0% and 0% for placebo (P = 0.0010 and P = 0.0013, respectively). Across four macaque studies, survival was 6.3% to 78.6% following 4 to 32 mg/kg obiltoxaximab. In two macaque studies, 16 mg/kg obiltoxaximab reduced toxemia and led to survival rates of 31%, 35%, and 47% versus 0%, 0%, and 6.3% with placebo (P = 0.0085, P = 0.0053, P = 0.0068). Pretreatment bacteremia and toxemia levels inversely correlated with survival. Overall, obiltoxaximab monotherapy neutralized PA and increased survival across the range of disease severity, indicating clinical benefit of toxin neutralization with obiltoxaximab in both early and late stages of inhalational anthrax.

An Aggregate of Four Anthrax Cases during the Dry Summer of 2011 in Epirus, Greece.

BACKGROUND: Human anthrax is currently a sporadic disease in Europe, without significant regional clustering. OBJECTIVE: To report an unexpected aggregate of anthrax cases and correlate local climatic factors with yearly anthrax admissions. METHODS: Clinical description of a geographical-temporal anthrax aggregate, correlation of disease admissions with local weather data in the period 2001-2014 and literature reports of anthrax clusters from Europe in the last 20 years. RESULTS: We identified 5 cases, all cutaneous: an unexpected aggregate of 4 cases in mid-summer 2011 (including a probable human-to-human transmission) and a sporadic case in August 2005, all in relatively dry periods (p < 0.05). Remarkably, 3/6 reports of human anthrax aggregates from Europe were observed in Balkan Peninsula countries in the year 2011. CONCLUSION: In the light of the predicted climatic change, unexpected anthrax aggregates during dry periods in southern Europe underscore the risk of future anthrax re-emergence on this continent.

Anthrax in injecting drug users: the need for increased vigilance in the clinic.

The emergence of a previously unrecognized route of Bacillus anthracis infection over the last few years has led to concern: sporadic anthrax outbreaks among heroin users in northern Europe have demonstrated the severe pathology associated with the newly described 'injectional anthrax'. With a high case fatality rate and non-specific early symptoms, this is a novel clinical manifestation of an old disease. Lack of awareness of this syndrome among emergency room clinicians can lead to a delayed diagnosis among heroin users; indeed, for many health workers in developed countries, where infection by B. anthracis is rare, this may be the first time they have encountered anthrax infections. As the putative route of contamination of the heroin supply is potentially ongoing, it is important that clinicians and public health workers remain vigilant for early signs of injectional anthrax.

Injectional anthrax at a Scottish district general hospital.

This retrospective, descriptive case-series reviews the clinical presentations and significant laboratory findings of patients diagnosed with and treated for injectional anthrax (IA) since December 2009 at Monklands Hospital in Central Scotland and represents the largest series of IA cases to be described from a single location. Twenty-one patients who fulfilled National Anthrax Control Team standardized case definitions of confirmed, probable or possible IA are reported. All cases survived and none required limb amputation in contrast to an overall mortality of 28% being experienced for this condition in Scotland. We document the spectrum of presentations of soft tissue infection ranging from mild cases which were managed predominantly with oral antibiotics to severe cases with significant oedema, organ failure and coagulopathy. We describe the surgical management, intensive care management and antibiotic management including the first description of daptomycin being used to treat human anthrax. It is noted that some people who had injected heroin infected with Bacillus anthracis did not develop evidence of IA. Also highlighted are biochemical and haematological parameters which proved useful in identifying deteriorating patients who required greater levels of support and surgical debridement.

Injectional anthrax - new presentation of an old disease.

Bacillus anthracis infection (anthrax) has three distinct clinical presentations depending on the route of exposure: cutaneous, gastrointestinal and inhalational anthrax. Each of these can lead to secondary bacteraemia and anthrax meningitis. Since 2009,anthrax has emerged among heroin users in Europe,presenting a novel clinical manifestation, 'injectional anthrax', which has been attributed to contaminated heroin distributed throughout Europe; before 2009 only one case was reported. During 2012 and 2013,new cases of injectional anthrax were diagnosed in Denmark, France, Germany, and the United Kingdom.Here we present a comprehensive review of the literature and information derived from different reporting systems until 31 December 2013. Overall 70 confirmed cases were reported, with 26 fatalities (37% case fatality rate).The latest two confirmed cases occurred in March 2013. Thirteen case reports have been published,describing 18 confirmed cases. Sixteen of these presented as a severe soft tissue infection that differed clinically from cutaneous anthrax, lacked the characteristic epidemiological history of animal contact and ten cases required complimentary surgical debridement. These unfamiliar characteristics have led to delays of three to 12 days in diagnosis, inadequate treatment and a high fatality rate. Clinicians' awareness of this recently described clinical entity is key for early 'and successful management of patients.

Cutaneous anthrax in a school teacher.

Cutaneous anthrax is an infection of the skin caused by Bacillus anthracis. This is a report of a case of cutaneous anthrax attending outpatients of Mymensingh Medical College Hospital in October, 2010. The infected person was a retired school teacher with a very good body build. He reported to handle cow flesh about 4-5 days ago, developed few painless papules over shin of right leg, which gradually became large bullae and blackish eschar developed over the lesion. Smears from the lesions were investigated which confirmed the causative agent B. anthracis. The patient was treated with oral Ciprofloxacin (500mg) twice daily for seven days which cured the infection as observed on his subsequent follow up visits on 7 and 14 days later. Oral Ciprofloxacin is found effective as recommended by the World Health Organization.

[Anthrax meningoencephalitis: a case following a cutaneous lesion in Morocco]. / Atteinte cérébroméningée de la maladie de charbon: à propos d'un cas à point de départ cutané au Maroc.

Anthrax meningoencephalitis is very rare especially following skin location. We report a case of meningoencephalitis secondary to skin lesion. The diagnosis is based on clinical presentation and confirmed by microbiological tests. Its evolution remains fatal despite aggressive resuscitation.

Anthrax: a case report.

Anthrax is a zoonotic disease caused by a bacterium called Bacillus Anthracis. In humans, it causes a cutaneous, gastro-intestinal and inhalation form of disease. The in-cutaneous form progresses along with skin necrosis and oedema. Since the necroses in the skin are not quite superficial, they can affect the tendon sheaths progressing close to the skin. Therefore, in surgical treatment, the closure in the areas where tendons are surfaced must be provided by a flap instead of a graft.The repair on the existing patient was performed with a graft since the flap repair was not accepted, and thus, restrictions in hand movements occurred during the post-operative period.

Injection anthrax--a new outbreak in heroin users.

BACKGROUND: Injection anthrax is a rare disease that affects heroin users and is caused by Bacillus anthracis. In 2012, there were four cases in Germany, one of which was fatal, as well as a small number of cases in other European countries, including Denmark, France, and the United Kingdom. Three cases among drug users occurred in Germany in 2009/2010, in the setting of a larger outbreak centered on Scotland, where there were 119 cases. CASE PRESENTATION AND CLINICAL COURSE: We present three cases of injection anthrax, two of which were treated in Regensburg and one in Berlin. One patient died of multi-organ-system failure on the day of admission to the hospital. The others were treated with antibiotics, one of them also with surgical wound debridement. The laboratory diagnosis of injection anthrax is based on the demonstration of the pathogen, generally by culture and/or by polymerase chain reaction, in material removed directly from the patient's wound. The diagnosis is additionally supported by the detection of specific antibodies. CONCLUSION: Injection anthrax may be viewed either as an independent disease entity or as a special type of cutaneous anthrax with massive edema, necrotizing fasciitis in many cases, and about 30% mortality. It has appeared in recent years among heroin users in various European countries. In patients with suggestive clinical presentation and a history of heroin use, anthrax infection must be suspected early, so that the appropriate diagnostic tests can be performed without delay. Timely treatment can be life-saving. It is therefore important that physicians--and the individuals at risk--should be well-informed about this disease.

Fatal anthrax infection in a heroin user from southern Germany, June 2012.

Blood cultures from a heroin user who died in June 2012, a few hours after hospital admission, due to acute septic disease, revealed the presence of Bacillus anthracis. This report describes the extended diagnosis by MALDI-TOF and real-time PCR and rapid confirmation of the anthrax infection through reference laboratories. Physicians and diagnostic laboratories were informed and alerted efficiently through the reporting channels of German public health institutions, which is essential for the prevention of further cases.

An overview of anthrax infection including the recently identified form of disease in injection drug users.

PURPOSE: Bacillus anthracis infection (anthrax) can be highly lethal. Two recent outbreaks related to contaminated mail in the USA and heroin in the UK and Europe and its potential as a bioterrorist weapon have greatly increased concerns over anthrax in the developed world. METHODS: This review summarizes the microbiology, pathogenesis, diagnosis, and management of anthrax. RESULTS AND CONCLUSIONS: Anthrax, a gram-positive bacterium, has typically been associated with three forms of infection: cutaneous, gastrointestinal, and inhalational. However, the anthrax outbreak among injection drug users has emphasized the importance of what is now considered a fourth disease form (i.e., injectional anthrax) that is characterized by severe soft tissue infection. While cutaneous anthrax is most common, its early stages are distinct and prompt appropriate treatment commonly produces a good outcome. However, early symptoms with the other three disease forms can be nonspecific and mistaken for less lethal conditions. As a result, patients with gastrointestinal, inhalational, or injectional anthrax may have advanced infection at presentation that can be highly lethal. Once anthrax is suspected, the diagnosis can usually be made with gram stain and culture from blood or tissue followed by confirmatory testing (e.g., PCR). While antibiotics are the mainstay of anthrax treatment, use of adjunctive therapies such as anthrax toxin antagonists are a consideration. Prompt surgical therapy appears to be important for successful management of injectional anthrax.