Cutaneous anthrax associated with facial palsy:A case report

Rationale:Anthrax is a zoonotic disease caused by spores of Gram-positive Bacillus anthracis,commonly affects mammals and in rare cases birds.Human infection occurs accidentally through direct or indirect exposure to animal or their products.Patient concerns:A 63-year-old man was referred to our hospital with flu-like symptoms and severe swelling and redness on the face,the roof of the mouth,and nostrils.He had a history of direct contact with a slaughtered mutton two days ago.He declared controlled diabetes,hypertension,hypertriglyceridemia,and heart failure.Lungs were normal in lung high resolution CT,but multiple lymphadenopathies were seen in the mediastinum.Bilateral axillary lymphadenopathy with a maximum sad of 23 mm and pleural effusion on the right side was observed.CT scan of the nose and sinuses showed an increased density of polyps in the left maxillary sinus.Slides were prepared from the patient's lesions and examined under a light microscope.Bacillus shape with Streptococcus bacteria was seen.Diagnosis:Anthrax co-infection with herpes systemic virus and Streptococcus pyogenes.Interventions:Multidrug therapy started with appropriate antibiotics.Outcomes:The symptoms of the patient gradually disappeared.The patient was discharged without any complications.Lessons:Cutaneous anthrax in endemic areas in patients with skin presentations and a history of contact with infected animals or products should be considered a differential diagnosis.This is more important in mixed infections where the main cause of the problem may be hidden.

Anthrax: A disease of biowarfare and public health importance

Bioterrorism has received a lot of attention in the first decade of this century. Biological agents are considered attractive weapons for bioterrorism as these are easy to obtain, comparatively inexpensive to produce and exhibit widespread fear and panic than the actual potential of physical damage. Bacillus anthracis(B. anthracis), the etiologic agent of anthrax is a Gram positive, spore forming, non-motile bacterium. This is supposed to be one of the most potent BW agents because its spores are extremely resistant to natural conditions and can survive for several decades in the environment. B.anthracis spores enter the body through skin lesion(cutaneous anthrax), lungs(pulmonary anthrax), or gastrointestinal route(gastrointestinal anthrax) and germinate, giving rise to the vegetative form. Anthrax is a concern of public health also in many countries where agriculture is the main source of income including India. Anthrax has been associated with human history for a very long time and regained its popularity after Sept 2001 incidence in United States. The present review article describes the history, biology, life cycle, pathogenicity, virulence, epidemiology and potential of B. anthracis as biological weapon.

Anthrax:an update

Anthrax is a zoonotic disease caused by Bacillus anthracis.It is potentially fatal and highly contagious disease.Herbivores arc the natural host.Human acquire the disease incidentally by contact with infected animal or animal products.In the 18th century an epidemic destroyed approximately half of the sheep in Europe.In 1900 human inhalational anthrax occured sporadically in the United Stales.In 1979 an outbreak of human anthrax occured in Sverdlovsk of Soviet Union.Anthrax continued to represent a world wide presence.The incidence of the disease has decreased in developed countries as a result of vaccination and improved industrial hygiene.Human anthrax clinically presents in three forms,i.e.cutaneous,gastrointestinal and inhalational.About 95%of human anthrax is cutaneous and 5%is inhalational.Gastrointestinal anthrax is very rare(less than 1%).Inhalational form is used as a biological warefare agent. Penicillin,ciprofloxacin(and other quinolones),doxicyclin,ampicillin,imipenem.clindamycin, clarithromycin,vancomycin,chloramphenicol,rifampicin are effective antimicrobials. Antimicrobial therapy for 60 days is recommended.Human anthrax vaccine is available. Administration of anti-protective antigen(PA) antibody in combination with ciprofloxacin produced 90%-100%survival.The combination of CPG-adjuvanted anthrax vaccine adsorbed(AVA) plus dalbavancin significantly improved survival.

Latest therapeutic target for gastric cancer:Anthrax toxin receptor 1

Anthrax toxin receptor 1(ANTXR1),also known as tumor endothelial marker 8,is a highly conserved cell surface protein overexpressed in tumor-infiltrating vessels.It was first found in vascular endothelial cells of human colorectal cancer.Although our understanding of its physiological function is limited,it has been found that ANTXR1 binds collagen and promotes migration of endothelial cells in vitro.ANTXR1 is upregulated in vessels of different tumor types in mice and humans,and is also expressed by tumor cells themselves in some tumors,such as gastric,lung,intestinal and breast cancer.Developmental angiogenesis and wound healing were not disturbed in ANTXR1 knockout mice,but compared with wild-type mice,growth of melanoma was impaired after ANTXR1 knockout,indicating that host-derived ANTXR1 can promote tumor growth on the basis of immune activity.Previous studies have shown that ANTXR1 vaccines or sublethal doses of anthrax toxin can inhibit angiogenesis,slow tumor growth and prolong survival.These studies suggest that ANTXR1 is necessary for tumor rather than physiological angiogenesis.It has been found that ANTXR1 plays an important role in tumor angiogenesisas well as in the growth and metastasis of many kinds of tumors.This article reviews the physiological function of ANTXR1 and its role in different kinds of cancer.

Anthrax lethal toxin suppresses high glucose induced VEGF over secretion through a post-translational mechanism

AIM: To prove anthrax lethal toxin(Le Tx) blocks the mitogen activated protein kinases(MAPKs) activation by degrading the MAPK/ERK kinases(MEKs) to suppress vascular endothelial growth factor(VEGF) secretion.METHODS: Human adult retinal pigmented epithelium(ARPE) cells were cultured and treated with normal glucose, high glucose or high glucose with Le Tx for additional 24, 48 or 72 h for viable cell count. Total RNA from the ARPE was isolated for reverse transcription polymerase chain reaction(RT-PCR). The conditioned medium of ARPE cells treated in different group for 48 h was filtered and diluted to detect the concentration of VEGF by enzyme-linked immunosorbant assays.Evaluate the role of MEK/MAPK pathway in the secretion of VEGF by immunoblotting. RESULTS: In this study, we proved high glucose induced activation of the MAPK extracellular signal-regulated kinase(ERK1/2) and p38 in the ARPE cell line was blocked by anthrax Le Tx. Le Tx also inhibited high glucose induced ARPE cell over proliferation.CONCLUSION: Le Tx suppressed high glucose induced VEGF over secretion in the ARPE cells, mainly through a post-translational mechanism.

Spatial distribution of cutaneous anthrax in western Iran from 2009 to 2016:Geographic information system mapping for predicting risk of anthrax outbreaks

Objective:To explore the spatial accumulation of diseases andtheir aggravating factors are essential in all public health.This study attempts to use geographic information system(GIS)to provide more information about the incidence and future of anthrax.Methods:Patients were diagnosed with anthrax in Kurdistan Province from 2009 to 2016.Data was then exported into ArcGIS software version 9 and the required layers for years and areas were added.Final map for each year was drawn up,pointing out the hot spots and predicting its future pattern.Results:Most cases were reported in females(57 cases,54.80%),and the lower body limbs were most affected(63 cases,60.57%).The highest numbers of incidences were related to the cities of Marivan,Saqez and Divandareh,with more concentration in the central parts of the province,rather than borderline areas.The highest percentage of the probable incidence of the disease was in Sanandaj(57.74%)with a potential susceptible area of 1729.12 km2 and then in Saqez(54.36%)with a potential area of 2422.4 km2.Conclusions:A vast area of Kurdistan Province is high risk for new cases of anthrax.Therefore,it is important to scale up the surveillance system in the province.

Targeting the inflammasome and adenosine type-3 receptors improves outcome of antibiotic therapy in murine anthrax

AIM:To establish whether activation of adenosine type-3 receptors(A3Rs)and inhibition of interleukin- 1β-induced inflammation is beneficial in combination with antibiotic therapy to increase survival of mice challenged with anthrax spores. METHODS:DBA/2 mice were challenged with Bacillus anthracis spores of the toxigenic Sterne strain 43F2. Survival of animals was monitored for 15 d.Ciprofloxacin treatment(50 mg/kg,once daily,intraperitoneally) was initiated at day+1 simultaneously with the ad- ministration of inhibitors,and continued for 10 d.Two doses(2.5 mg/kg and 12.5 mg/kg)of acetyl-tyrosylvalyl-alanyl-aspartyl-chloromethylketone(YVAD)and three doses(0.05,0.15 and 0.3 mg/kg)of 1-[2-Chloro- 6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1- deoxy-N-methyl-β-D-ribofuranuronamide(Cl-IB-MECA) were tested.Animals received YVAD on days 1-4,and Cl-IB-MECA on days 1-10 once daily,subcutaneously. Human lung epithelial cells in culture were challenged with spores or edema toxin and the effects of IB-MECAon phosphorylation of AKT and generation of cAMP were tested. RESULTS:We showed that the outcome of antibiotic treatment in a murine anthrax model could be substantially improved by co-administration of the caspase-1/4 inhibitor YVAD and the A3R agonist Cl-IB-MECA.Combination treatment with these substances and ciprofloxacin resulted in up to 90%synergistic protection.All untreated mice died,and antibiotic alone protected only 30% of animals.We conclude that both substances target the aberrant host signaling that underpins anthrax mortality. CONCLUSION:Our findings suggest new possibilities for combination therapy of anthrax with antibiotics,A3R agonists and caspase-1 inhibitors.

Modeling Anthrax with Optimal Control and Cost Effectiveness Analysis

Anthrax is an infection caused by bacteria and it affects both human and animal populations. The disease can be categorized under zoonotic diseases and humans can contract infections through contact with infected animals, ingest contaminated dairy and animal products. In this paper, we developed a mathematical model for anthrax transmission dynamics in both human and animal populations with optimal control. The qualitative solution of the model behaviour was analyzed by determining Rhv, equilibrium points and sensitivity analysis. A vaccination class was incorporated into the model with waning immunity. Local and global stability of the model’s equilibria was found to be locally asymptotically stable whenever Rhv Rhv. It was revealed that reducing animal and human interaction rate, would decrease Rhv. We extended the model to optimal control in order to find the best control strategy in reducing anthrax infections. It showed that the effective strategy in combating the anthrax epidemics is vaccination of animals and prevention of humans.

Recent Developments in the Nasal Immunization against Anthrax

Bacillus anthracis is the causative agent of anthrax, a bacterial infection with a high mortality rate [1-3]. Although anthrax infection can be cutaneous, gastrointestinal or pulmonary, the pulmonary form is the most deadly [2,3]. Thus, the release of Bacillus anthracis spores that can be inhaled represents a potent bioterrorism threat;the capacity of B. anthracis spores to act as a bioterrorism weapon was demonstrated in 2001, with the intentional infection of 22 persons in the U.S.A. [2,4]. Until recently, the available vaccines were developed to confer protection against cutaneous infection;despite this, these vaccines demonstrated experimental efficacy against pulmonary infection in multiple animal models [1,2]. Nevertheless, there are many limitations for these vaccines to be considered successful and effective vaccine, including the intensity of the required vaccination schedule, the administration route and the presence of local adverse effects experienced after vaccination [1,3,5,6]. To develop more efficient vaccines against pulmonary anthrax, intranasal formulations with adjuvant have been studied. These formulations have advantages because they are easy to administer and because they are expected to induce both systemic and respiratory tract mucosal immune responses. Therefore, the main goal of this review is to compare the different experimental adjuvants used with anthrax antigens and the different approaches regarding the vaccination schedule and consecutive boosters.

Recent Epidemic-Like Anthrax Outbreaks in Italy: What Are the Probable Causes?

In Italy, in an area of about 50 km2 between Basilicata and Campania Southern regions, 28 outbreaks of anthrax occurred from August 28th to September 27th 2011. Different species were affected: laboratory tests confirmed anthrax in cattle, horses and sheep. The genetic analysis of strains isolated from infected animals indicated that outbreaks occurring in the two regions were not correlated. Intriguingly, the incidence was highly significant in horses compared to that of cattle and sheep or goats, which were prevalent species in the animal population. In addition, allinfected horses and many cattle developed a fatal, sub-acute form of anthrax, characterized by the presence of massive edema, usually absent in hyperacute forms. The characteristics of these outbreaks suggested a possible role of tabanids as vectors in the transmission of B. anthracis like-epidemic infection.

Assessment of Knowledge,Attitude and Practices(KAPS)of Anthrax among Pastoralists in Wajir,Isiolo and Marsabit Counties,Kenya

Anthrax is an important zoonotic disease in Kenya causing high morbidity and mortality in both human and livestock.It is endemic in the country.The objective of this study was to assess the knowledge,attitude and practices(KAPS)of anthrax among pastoralists in Wajir,Isiolo and Marsabit.The study was cross-sectional whereby various areas of anthrax outbreaks were identified through the veterinary departments in the three study counties of Wajir,Isiolo and Marsabit.These areas were visited and using systematic sampling methods,a total of 400 households were visited.Data were collected through questionnaires administered via personal interviews.Information collected included demographic characteristics of the households,knowledge on anthrax,attitude and practices on the disease.Pastoralists had adequate knowledge on anthrax.They correctly pointed out the clinical signs of anthrax in livestock such as sudden death,bleeding from body orifices and cutanous sores.The indigenous knowledge was uniform in all the three counties.Despite that knowledge,they reportedly engaged in dangerous practices that would expose them to infection by anthrax.These practices included consumption of meat from suspect anthrax cases,opening of carcasses of dead animals and throwing of anthrax suspect carcasses in bushes.Anthrax is a well known disease in this pastoral setting.There is a need for education programmes to be designed for this community especially with regard to proper handling of suspect anthrax cases.Continuous anthrax efforts should be initiated through vaccination of livestock.

Gastrointestinal Anthrax:A Case and Review of Literature

Anthrax which is caused by Bacillus anthracis is typically a disease of herbivores. Spores existing in the skin, meat, hair or mouth and nose of animals are transmitted to humans through contact with a break in the skin, consumption of infected meat or inhalation of spores [1]. Infected uncooked or insufficiently cooked meats cause oropharyngeal and gastrointestinal system (GIS) anthrax. When this infected materials swallowed anthrax spores may cause lesions from the oral cavity to the caecum. The diagnosis of gastrointestinal system (GIS) anthrax is difficult due to insidious clinical progression of the disease and difficulty in the isolation of agent pathogen. Releated symptoms of GIS anthrax are sore throat, neck swelling, diffuculty swallowing, stomach pain, anoreksia, bloody diarrhea, nause, bloody vomiting and fever. Supportive and antibiotic treatments are required. Benzylpenicillin, rifampicin, clindamycin, chloramphenicol, imipenem/cilastatin, or vancomycin can be use for treatment, ciprofloxacin or doxycycline may be added to this treat- ment for serious cases. To emphasize the necessity of taking precautions, an oropharyngeal and intestinal anthrax case due to consumption of infected and insufficiently cooked meat is presented below.

Global dynamics in a model for anthrax transmission in animal populations

In this paper,we propose a deterministic model to study the transmission dynamics of anthrax disease,which includes live animals,carcasses,spores in the environment and vectors.We derive three biologically plausible and insightful quantities(reproduction numbers)that determine the stability of the equilibria.We carry out rigorous mathematical analysis on the model dynamics,the global stability of the disease-free and vector-free equilibrium,the disease-free equilibrium and the vector-free disease equilibrium is proved.The global stability of the endemic equilibrium as the basic reproduction number is greater than one is derived in the special case in which the disease-related death rate is zero.The possibility of backward bifurcation is briefly discussed.Numerical analyses are carried out to understand the transmission dynamics of anthrax and investigate effective control strategies for the outbreaks of the disease.Our studies suggest that the larval vector control measure should be taken as early as possible to control the vector population size,a vaccination policy and an animal carcass removal policy are useful methods to control the prevalence of the diseases in infected animal populations,the adult vector control measure is also necessary to prevent the transmission of anthrax.

基于两类媒介的炭疽传播模型的全局动力学分析

为了研究动物种群中媒介对炭疽传播的影响,该文依据尸食性蝇与血食性蝇的传播机制,建立了一个确定性传染病模型.利用微分方程基本定理证明了模型解的非负性和有界性,给出了平衡点存在的充分条件,定义了模型的几类再生数,利用线性化方法和M-矩阵等方法对平衡点的稳定性进行了分析,并研究了疾病的持久性.利用数值模拟研究了参数对基本再生数的影响.研究结果表明:及时清理染病尸体,尽量消除苍蝇的繁殖地点,对苍蝇使用杀虫剂对炭疽在动物种群中传播具有一定的抑制作用.

Genetic source tracking of an anthrax outbreak in Shaanxi province,China

Background:Anthrax is an acute zoonotic infectious disease caused by the bacterium known as Bacillus anthracis.From 26 July to 8 August 2015,an outbreak with 20 suspected cutaneous anthrax cases was reported in Ganquan County,Shaanxi province in China.The genetic source tracking analysis of the anthrax outbreak was performed by molecular epidemiological methods in this study.Methods:Three molecular typing methods,namely canonical single nucleotide polymorphisms(canSNP),multiple-locus variable-number tandem repeat analysis(MLVA),and single nucleotide repeat(SNR)analysis,were used to investigate the possible source of transmission and identify the genetic relationship among the strains isolated from human cases and diseased animals during the outbreak.Results:Five strains isolated from diseased mules were clustered together with patients’isolates using canSNP typing and MLVA.The causative B.anthracis lineages in this outbreak belonged to the A.Br.001/002 canSNP subgroup and the MLVA15-31 genotype(the 31 genotype in MLVA15 scheme).Because nine isolates from another four provinces in China were clustered together with outbreak-related strains by the canSNP(A.Br.001/002 subgroup)and MLVA15 method(MLVA15-31 genotype),still another SNR analysis(CL10,CL12,CL33,and CL35)was used to source track the outbreak,and the results suggesting that these patients in the anthrax outbreak were probably infected by the same pathogen clone.Conclusions:It was deduced that the anthrax outbreak occurred in Shaanxi province,China in 2015 was a local occurrence.

Can scavengers save zebras from anthrax? A modeling study

Namibia’s Etosha National Park(ENP)is home to many different animals such as lions,jackals,hyenas,zebras,elephants,etc.Each year,grazing animals are infected and die from anthrax caused by the bacteria Bacillus anthracis.This increases the number of carcasses in the park,which serve as food for scavengers such as jackals.This study investigates the interplay between anthrax transmission in zebras and the scavenging of zebra carcasses in ENP,using a deterministic mathematical model to describe the population dynamics.We strive to answer the following research questions:Under what conditions can the presence of scavengers control anthrax outbreaks in zebra populations=Does carcass production by anthrax help or hurt scavengers in the long term?Standard qualitative analysis techniques distinguished outcomes(stable equilibria)using reproduction numbers as threshold quantities.We found that,when scavengers feed on anthrax-laden carcasses,the scavengers help the zebras,by eliminating potential infection zones for the zebras.In this way they reduce anthrax’s spread by orders of magnitude.We also identify conditions under which the presence of anthrax benefits the scavengers,in terms of death-to-birth ratios for zebras,scavengers and anthrax.

Immunological dynamics in response to two anthrax vaccines in mice

In order to understand the variation of humoral and cellular immune responses to A16R live spore and AVA vaccine and to identify efficient immunological parameters for the early evaluation of post immu- nization in mice, we dynamically monitored the antibody production and cellular responses after the vaccination of Balb/C mice with the anthrax vaccines. The results show that both anti-AVA and anti-Spore antibodies were detectable in the A16R live spore vaccinated group while high titers of anti-AVA antibodies but not anti-Spore antibodies existed in the AVA-immunized group. IgG1 and IgG2 were the major subtypes of IgG in both of the two groups. However, the IgG2a level was significantly higher in the A16R group than in the AVA group. At the cellular level, responses of antigen-specific TH2, TH1 and plasma cells were detected. The peripheral TH2 responses could be seen on day 5 after vac- cination, and remained at a high level throughout the experiment (from day 5 post primary immuniza- tion to day 60 post the tertiary immunization); the TH1 responses to A16R vaccine appeared on day 5, while the responses to AVA could only be detected by day 7 after the secondary immunization; a low level of TH1 responses could be observed at the end of the experiment. Antigen-specific plasma cells could be found in the peripheral blood of both the immunized groups, however, the responses in the A16R group appeared earlier, lasted longer, and shown an ascending tendency until the end of the ex- periment when the plasma cell responses in the AVA group were reduced to a very low level. The re- sults suggest that the multiple antigen containing A16R live spore vaccine induces better immune re- sponses than AVA. Combined with serum antibody titers, TH2, TH1 and plasma cell responses could be used as immunological parameters for the evaluation of vaccine efficacy. These findings may afford new insight into the early evaluation of vaccination as well as being a powerful strategy for vaccine development.

AMPD3 is involved in anthrax LeTx-induced macrophage cell death

The responses of macrophages to Bacillus anthracis infection are important for the survival of the host,since macrophages are required for the germination of B.anthracis spores in lymph nodes,and macrophage death exacerbates anthrax lethal toxin(LeTx)-induced organ collapse.To elucidate the mechanism of macrophage cell death induced by LeTx,we performed a genetic screen to search for genes associated with LeTx-induced macrophage cell death.RAW264.7 cells,a macrophage-like cell line sensitive to LeTx-induced death,were randomly mutated and LeTx-resistant mutant clones were selected.AMP deaminase 3(AMPD3),an enzyme that converts AMP to IMP,was identified to be mutated in one of the resistant clones.The requirement of AMPD3 in LeTxinduced cell death of RAW 264.7 cells was confirmed by the restoration of LeTx sensitivity with ectopic reconstitution of AMPD3 expression.AMPD3 deficiency does not affect LeTx entering cells and the cleavage of mitogen-activated protein kinase kinase(MKK)by lethal factor inside cells,but does impair an unknown downstream event that is linked to cell death.Our data provides new information regarding LeTx-induced macrophage death and suggests that there is a key regulatory site downstream of or parallel to MKK cleavage that controls the cell death in LeTx-treated macrophages.

Anthrax,newly recorded from Vietnam(Diptera:Bombyliidae)

The genus Anthrax Scopoli, 1763 is newly recorded from Vietnam. Previously, there were just two genera, Systropus and Heteralonia, in Bombyliidae recorded from Vietnam. Genus Anthrax with 248 known species, has a worldwide distribution, of which 25 species are from the Oriental Region. One species A. dentata Becker, 1906 from Vietnam is redescribed. A key to the genera of Bombyliidae from Vietnam is presented.

Anthrax Scare Makes Paper Ban Letters to Editor

一份亚利桑那州的报纸,以全国陷入致命细菌的恐慌后对炭疽热的担忧为理由,决定放弃由来已久的接收读者通过美国邮政给编辑写信的惯例。