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PubMed2002

Self-reported changes in subjective health and anthrax vaccination as reported by over 900 Persian Gulf War era veterans.

A 1999 study of United Kingdom servicemembers by Unwin, et al. recently found significant relationships between anthrax and other vaccinations, reactions to those vaccines, and later health problems for male current or former active military Gulf War veterans. Likewise, in 2000 Steele and in 1998 Gilroy found possible adverse effects of vaccinations on Gulf War veterans. However, the role of such vaccinations remains controversial; more recent government reports continue to dispute the existence of any data that might reflect adversely on the role of vaccinations on the health of Gulf War veterans. To address this controversy, the current study assessed similar relationships for over 900 Reserve Component Gulf War Era veterans from Ohio and nearby states. Gulf War veterans were more likely to report poorer health than non-Gulf veterans. Female veterans were more likely to report mild or severe reactions to vaccines than male veterans. Those veterans who received anthrax vaccine reported more reactions to vaccines than those who did not receive anthrax vaccine. Declines in long-term subjective health were associated with receipt of anthrax vaccine by Gulf War veterans but not for those who did not deploy to the Gulf, although few of the latter received anthrax vaccine. Regardless of deployment status, veterans who reported more severe reactions to vaccines were more likely to report declines in subjective health. Female veterans reported poorer health during the Gulf War than did male veterans, but sex was not related to veterans' reports of subjective health at subsequent times. It is recommended that servicemembers who experience severe reactions to anthrax vaccine be medically reevaluated before receiving further anthrax vaccine and that careful follow-ups be conducted of those receiving the vaccine currently, in accordance with Nass's 1999 recommendations. We also recommend that safer alternatives to thimerosal (a mercury sodium salt, 50% mercury) be used to preserve all vaccines.

Adult↗
PubMed2002

Use of anthrax vaccine in response to terrorism: supplemental recommendations of the Advisory Committee on Immunization Practices.

In December 2000, the Advisory Committee on Immunization Practices (ACIP) released its recommendations for using anthrax vaccine in the United States. Because of recent terrorist attacks involving the intentional exposure of U.S. civilians to Bacillus anthracis spores and concerns that the current anthrax vaccine supply is limited, ACIP developed supplemental recommendations on using anthrax vaccine in response to terrorism. These recommendations supplement the previous ACIP statement in three areas: use of anthrax vaccine for pre-exposure vaccination in the U.S. civilian population, the prevention of anthrax by postexposure prophylaxis (PEP), and recommendations for additional research related to using antimicrobial agents and anthrax vaccine for preventing anthrax

Anthrax↗
PubMed2002

Relationship between prepregnancy anthrax vaccination and pregnancy and birth outcomes among US Army women.

CONTEXT: Substantial concern surrounds the potential health effects of the anthrax vaccine, particularly the potential adverse effects on reproductive processes. OBJECTIVE: To determine whether receipt of anthrax vaccination by reproductive-aged women has an effect on pregnancy rates. DESIGN, SETTING, AND PATIENTS: Cohort study, based on information from a computer database, of women aged 17 to 44 years who were stationed at Fort Stewart, Ga, or Hunter Army Airfield, Ga, from January 1999 through March 2000. MAIN OUTCOME MEASURES: Pregnancy and birth rates and adverse birth outcomes. RESULTS: Of a total of 4092 women, 3136 received at least 1 dose of the anthrax vaccine. There was a total of 513 pregnancies, with 385 following at least 1 dose of anthrax vaccine. The pregnancy rate ratio (before and after adjustment for marital status, race, and age) comparing vaccinated with unvaccinated women was 0.94 (95% confidence interval [CI], 0.8-1.2; P =.60). There were 353 live births and 25 pregnancies lost to follow-up. The birth odds ratio after anthrax vaccination (before and after adjustment for marital status and age) was 0.9 (95% CI, 0.5-1.4; P =.55). After adjusting for age, the odds ratio for adverse birth outcome after receiving at least 1 dose of anthrax vaccination was 0.9 (95% CI, 0.4-2.4; P =.88). However, this study did not have sufficient power to detect adverse birth outcomes. CONCLUSION: Anthrax vaccination had no effect on pregnancy and birth rates or adverse birth outcomes.

Adolescent↗
PubMed2000

Vaccines for preventing anthrax.

BACKGROUND: Anthrax is an acute bacterial skin disease which may be fatal. Three anthrax vaccines are commercially available but their comparative effectiveness and safety is not clear. OBJECTIVES: The objective of this review was to assess the effects of human anthrax vaccines in healthy adults and children. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, Medline, Embase and the reference lists of articles. We handsearched the journal Vaccine and contacted researchers in the field. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing anthrax vaccines with placebo, vaccines for other diseases or no intervention. DATA COLLECTION AND ANALYSIS: Trial quality assessment and data extraction was conducted independently by the six authors. MAIN RESULTS: Two trials involving 16,052 people were included. Both trials had methodological limitations. Compared to placebo, vaccination was associated with a reduced risk of contracting anthrax (relative risk 0.16, 95% confidence interval 0.07 to 0.35). Compared to placebo, the killed vaccine was associated with a higher incidence and severity of adverse effects (odds ratio 5.15, 95% confidence interval 2.28 to 11.61). Just over 5% of participants in the vaccine group reported adverse effects. The effectiveness of the vaccine does not appear to be influenced by the route of inoculation. REVIEWER'S CONCLUSIONS: Killed anthrax vaccines appear to be effective in reducing the risk of contracting anthrax with a relatively low rate of adverse effects. Further research should be restricted to testing new vaccines only.

Adult↗
PubMed2006

Treatment and prophylaxis of anthrax by new neurosecretory cytokines.

In 1881, Louis Pasteur described the Bacillus anthracis vaccine, which plays an important role for the treatment and prophylaxis of anthrax. Currently, treatment for anthrax infection involves the use of several different antibiotics, used in combination with vaccines, which possess potential virulence in white mice and guinea pigs. We discovered several new immunomodulators cytokines (polypeptides) produced by the neurosecretory cells of hypothalamus, some of which can be used as drugs for the treatment and prophylaxis of the anthrax. The proline-rich polypeptides, which consist from 10 to 15 amino acids and four proline residues, are of the special interest; one of them (PRP-1), which consist of 15 amino acids and has the following primary structure ALa-GLy-ALa-Pro-GLu-Pro-Ala-GLu-Pro-Ala-GLn-Pro-GLy-Val-Tyr (AGAPEPAEPAQPGVY) possesses antibacterial activity, and a new proline-rich peptide described by Galoyan and called Gx-NH2. Both were tested for treatment against the anthrax bacillus or anthrax strain N55 vaccine in guinea pigs and mice in vivo, and in vitro preparations. The results of experiments show that these hypothalamic neurosecretory cytokines have a strong prophylaxis and therapeutic properties towards animals infected by episodic strain of anthrax and anthrax vaccine N55. The conventional concepts concerning the function of hypothalamic neurosecretion and hypothalamic mechanisms of adaptation have to be reconsidered.

Amino Acid Sequence↗
PubMed2006

Strong mucosal and systemic immunities induced by nasal immunization with anthrax protective antigen protein incorporated in liposome-protamine-DNA particles.

PURPOSE: The very lengthy and complicated dosing schedule of the current anthrax vaccine adsorbed, which was licensed in the USA for the prevention of cutaneous anthrax infection, calls for the development of an efficacious and easily administrable vaccine to prevent against the most lethal form of anthrax infection, the inhalation anthrax. We propose to develop a nasal anthrax vaccine using anthrax protective antigen (PA) protein carried by liposome-protamine-DNA (LPD) particles. METHODS: PA was incorporated in LPD particles and nasally dosed to mice. The resulting PA-specific immune response and lethal toxin neutralization activity were measured. RESULTS: Mice nasally immunized with PA incorporated into LPD particles developed both systemic and mucosal anti-PA responses. The anti-PA immunities induced included the production of anti-PA antibodies (IgG and IgM in the serum and IgA in nasal and lung mucosal secretions) and the proliferation of splenocytes after in vitro stimulation. The anti-PA IgG subtype induced was mainly IgG1. Finally, anthrax lethal toxin neutralization activity was detected both in the serum and in the mucosal secretions. CONCLUSIONS: The anti-PA immune response induced by nasal PA incorporated in LPD was comparable to that induced by nasal PA adjuvanted with cholera toxin or subcutaneously injected PA adjuvanted with aluminum hydroxide.

Administration, Intranasal↗
PubMed2003

Deletion mutants of protective antigen that inhibit anthrax toxin both in vitro and in vivo.

The anthrax toxin complex is primarily responsible for most of the symptoms of anthrax. This complex is composed of three proteins, anthrax protective antigen, anthrax edema factor, and anthrax lethal factor. The three proteins act in binary combination of protective antigen plus edema factor (edema toxin) and protective antigen plus lethal factor (lethal toxin) that paralyze the host defenses and eventually kill the host. Both edema factor and lethal factor are intracellularly acting proteins that require protective antigen for their delivery into the host cell. In this study, we show that deletion of certain residues of protective antigen results in variants of protective antigen that inhibit the action of anthrax toxin both in vitro and in vivo. These mutants protected mice against both lethal toxin and edema toxin challenge, even when injected at a 1:8 ratio relative to the wild-type protein. Thus, these mutant proteins are promising candidates that may be used to neutralize the action of anthrax toxin.

Animals↗
PubMed2003

Anthrax toxin receptor proteins.

Anthrax toxin is a key virulence factor for Bacillus anthracis, the causative agent of anthrax. Here we discuss what is known about the anthrax toxin receptor (ATR), the cellular receptor for anthrax toxin, and how this information is being used to develop treatments for anthrax as well as to understand aspects of cancer. ATR was identified recently as a type I transmembrane protein with unknown function that contains an extracellular integrin-like inserted (I) domain. The ATR I domain contains the toxin binding site, and a soluble form of this domain was shown to serve as an effective antitoxin to protect cultured cells from toxin action. ATR is encoded by the tumor endothelial marker 8 (TEM8) gene, which is selectively up-regulated during blood vessel formation and in tumor vasculature, raising the possibility that this protein normally functions in angiogenesis. Therefore, identification of the cellular receptor for anthrax toxin has made possible new avenues of research in the areas of anthrax pathogenesis, antitoxin development, and cancer biology.

Animals↗
PubMedDate not supplied

Clinical predictors of bioterrorism-related inhalational anthrax.

Limitation of a bioterrorist anthrax attack will require rapid and accurate recognition of the earliest victims. To identify clinical characteristics of inhalational anthrax, we compared 47 historical cases (including 11 cases of bioterrorism-related anthrax) with 376 controls with community-acquired pneumonia or influenza-like illness. Nausea, vomiting, pallor or cyanosis, diaphoresis, altered mental status, and raised haematocrit were more frequently recorded in the inhalational anthrax cases than in either the community-acquired pneumonia or influenza-like illness controls. The most accurate predictor of anthrax was mediastinal widening or pleural effusion on a chest radiograph. This finding was 100% sensitive (95% CI 84.6-100.0) for inhalational anthrax, 71.8% specific (64.8-78.1) compared with community-acquired pneumonia, and 95.6% specific (90.0-98.5) compared with influenza-like illness. Our findings represent preliminary efforts toward identifying clinical predictors of inhalational anthrax.

Aerosols↗
PubMed1992

Serology and anthrax in humans, livestock and Etosha National Park wildlife.

Results are presented from a number of epidemiological studies using enzyme immunoassays (EIA) based on the purified anthrax toxin antigens, protective antigen, lethal factor and oedema factor. Studies on sera from a group of 62 human anthrax patients in Turkey and from cattle in Britain following two unrelated outbreaks of anthrax show that EIA using protective antigen can be a useful diagnostic aid and will detect subclinical infections in appropriate circumstances. A serological survey on wildlife in the Etosha National Park, Namibia, where anthrax is endemic, showed that naturally acquired anthrax-specific antibodies are rare in herbivores but common in carnivores; in carnivores, titres appear to reflect the prevalence of anthrax in their ranges. Problems, as yet unresolved, were encountered in studies on sera from pigs following an outbreak of anthrax on a farm in Wales. Clinical details, including treatment, of the human and one of the bovine outbreaks are summarized and discussed in relation to the serological findings.

Adolescent↗
PubMed2005

No evidence of a mild form of inhalational Bacillus anthracis infection during a bioterrorism-related inhalational anthrax outbreak in Washington, D.C., in 2001.

BACKGROUND: The mail-related dispersal of Bacillus anthracis spores in the Washington, D.C., area during October 2001 resulted in 5 confirmed cases of inhalational anthrax. We identified an additional 144 ill persons who were potentially exposed to aerosolized spores and whose symptoms were compatible with early inhalational anthrax but whose clinical course and nonserologic laboratory evaluation revealed no evidence for B. anthracis infection. We hypothesized that early antibiotic use could have decreased the sensitivity of diagnostic tests or that bioterrorism-related inhalational anthrax may include mild disease. METHODS: Eligible patients included those with illness compatible with early inhalational anthrax who had potential exposure to B. anthracis. Patient serum samples were tested for immunoglobulin G (IgG) antibody against B. anthracis protective antigen (PA) using a sensitive enzyme-linked immunosorbant assay (sensitivity, 97.6%). RESULTS: Of the 144 eligible patients, 66 (46%) had convalescent-phase serum samples available for testing; 29 (44%) worked in an area considered to pose a high risk of exposure to B. anthracis spores. Of the 37 patients who worked in areas that did not meet the definition of high-risk exposure, 23 (62%) worked in United States postal or other government facilities in which exposure was plausible but not documented. None of the 66 patients with convalescent-phase serum samples showed evidence of an anti-PA IgG serologic response to B. anthracis. CONCLUSIONS: These data suggest that a mild form of inhalational anthrax did not occur and that surveillance for moderate or severe illness was adequate to identify all inhalational anthrax cases resulting from the Washington, D.C., bioterrorism-related anthrax exposures.

Adult↗
PubMed2006

Detection of anthrax toxin in the serum of animals infected with Bacillus anthracis by using engineered immunoassays.

Several strategies that target anthrax toxin are being developed as therapies for infection by Bacillus anthracis. Although the action of the tripartite anthrax toxin has been extensively studied in vitro, relatively little is known about the presence of toxins during an infection in vivo. We developed a series of sensitive sandwich enzyme-linked immunosorbent assays (ELISAs) for detection of both the protective antigen (PA) and lethal factor (LF) components of the anthrax exotoxin in serum. The assays utilize as capture agents an engineered high-affinity antibody to PA, a soluble form of the extracellular domain of the anthrax toxin receptor (ANTXR2/CMG2), or PA itself. Sandwich immunoassays were used to detect and quantify PA and LF in animals infected with the Ames or Vollum strains of anthrax spores. PA and LF were detected before and after signs of toxemia were observed, with increasing levels reported in the late stages of the infection. These results represent the detection of free PA and LF by ELISA in the systemic circulation of two animal models exposed to either of the two fully virulent strains of anthrax. Simple anthrax toxin detection ELISAs could prove useful in the evaluation of potential therapies and possibly as a clinical diagnostic to complement other strategies for the rapid identification of B. anthracis infection.

Animals↗
PubMed2006

Human monoclonal anti-protective antigen antibody completely protects rabbits and is synergistic with ciprofloxacin in protecting mice and guinea pigs against inhalation anthrax.

Prevention of inhalation anthrax requires early and extended antibiotic therapy, and therefore, alternative treatment strategies are needed. We investigated whether a human monoclonal antibody (AVP-21D9) to protective antigen (PA) would protect mice, guinea pigs, and rabbits against anthrax. Control animals challenged with Bacillus anthracis Ames spores by the intranasal route died within 3 to 7 days. AVP-21D9 alone provided minimal protection against anthrax in the murine model, but its efficacy was notably better in guinea pigs. When Swiss-Webster mice, challenged with five 50% lethal doses (LD50s) of anthrax spores, were given a single 16.7-mg/kg of body weight AVP-21D9 antibody dose combined with ciprofloxacin (30 mg/kg/day for 6 days) 24 h after challenge, 100% of the mice were protected for more than 30 days, while ciprofloxacin or AVP-21D9 alone showed minimal protection. Similarly, when AVP-21D9 antibody (10 to 50 mg/kg) was combined with a low, nonprotective dose of ciprofloxacin (3.7 mg/kg/day) and administered to guinea pigs for 6 days, synergistic protection against anthrax was observed. In contrast, a single dose of AVP-21D9 antibody (1, 5, 10, or 20 mg/kg) but not 0.2 mg/kg alone completely protected rabbits against challenge with 100 LD50s of B. anthracis Ames spores, and 100% of the rabbits survived rechallenge. Further, administration of AVP-21D9 (10 mg/kg) to rabbits at 0, 6, and 12 h after challenge with anthrax spores resulted in 100% survival; however, delay of antibody treatment by 24 and 48 h reduced survival to 80% and 60%, respectively. Serological analysis of sera from various surviving animals 30 days postprimary infection showed development of a species-specific PA enzyme-linked immunosorbent assay antibody titer that correlated with protection against reinfection. Taken together, the effectiveness of human anti-PA antibody alone or in combination with low ciprofloxacin levels may provide the basis for an improved strategy for prophylaxis or treatment following inhalation anthrax infection.

Administration, Inhalation↗
PubMed2004

The dissemination of anthrax from imported wool: Kidderminster 1900-14.

BACKGROUND: A century ago anthrax was a continuing health risk in the town of Kidderminster. The distribution of cases in people and in animals provides an indication of the routes by which spores were disseminated. The response to these cases provides an insight into attitudes to an occupational and environmental risk at the time and can be compared with responses in more recent times. AIMS: To assess the distribution of anthrax cases associated with the use of contaminated wool and to review the response to them. METHODS: The area studied was Kidderminster, Worcestershire, England, from 1900 to 1914. Data sources were national records of the Factory Inspectorate and local records from the infirmary, Medical Officer of Health and inquest reports, and county agricultural records, supplemented by contemporary and later review articles. Case reports and summary data were analysed, and discussions and actions taken to improve precautions reviewed. RESULTS: There were 36 cases of anthrax, with five deaths, one of which was the sole case of the internal form of the disease. Cases of cutaneous anthrax were most frequently found in those handling raw wool, but they also occurred in workers at later stages of the spinning process and in people with little or no recorded exposure to contaminated wool. Limited precautionary measures were in place at the start of the study period. Some improvements were made, especially in the treatment of infections, but wool with a high risk of anthrax contamination continued to be used and cases continued to arise. Major changes were made to the disposal of waste and to agricultural practice in contaminated areas to curtail outbreaks in farm animals. CONCLUSIONS: The introduction of anthrax as a contaminant of imported wool led not only to cases in the highly exposed groups of workers but also to cases in other members of the population and in farm animals. The measures taken during the study period reduced fatalities from cutaneous anthrax but did not eliminate the disease. Public concern about the cases was muted.

Animals↗
PubMed1999

Inhalational anthrax: epidemiology, diagnosis, and management.

Anthrax, a disease of great historical interest, is once again making headlines as an agent of biological warfare. Bacillus anthracis, a rod-shaped, spore-forming bacterium, primarily infects herbivores. Humans can acquire anthrax by agricultural or industrial exposure to infected animals or animal products. More recently, the potential for intentional release of anthrax spores in the environment has caused much concern. The common clinical manifestations of anthrax are cutaneous disease, pulmonary disease from inhalation of anthrax spores, and GI disease. The course of inhalational anthrax is dramatic, from the insidious onset of nonspecific influenza-like symptoms to severe dyspnea, hypotension, and hemorrhage within days of exposure. A rapid decline, culminating in septic shock, respiratory distress, and death within 24 h is not uncommon. The high mortality seen in inhalational anthrax is in part due to delays in diagnosis. Classic findings on the chest radiograph include widening of the mediastinum as well as pleural effusions. Pneumonia is less common; key pathologic manifestations include severe hemorrhagic mediastinitis, diffuse hemorrhagic lymphadenitis, and edema. Diagnosis requires a high index of suspicion. Treatment involves supportive care in an intensive care facility and high doses of penicillin. Resistance to third-generation cephalosporins has been noted. Vaccines are currently available and have been shown to be effective against aerosolized exposure in animal studies.

Animals↗
PubMed1993

Surveillance and control of anthrax and rabies in wild herbivores and carnivores in Namibia.

Anthrax has been studied intensively in Etosha National Park, Namibia since 1966; in addition, since 1975, mortality due to rabies and all other causes has been recorded, totalling 6,190 deaths. Standard diagnostic procedures demonstrated that at least 811 deaths (13%) were due to anthrax and 115 deaths (2%) were caused by rabies. Of the total number of deaths due to anthrax, 97% occurred in zebra (Equus burchelli), elephant (Loxodonta africana), wildebeest (Connochaetes taurinus) and springbok (Antidorcas marsupialis) while 96% of rabies deaths occurred in kudu (Tragelaphus strepsiceros), jackal (Canis mesomelas), bat-eared fox (Otocyon megalotis) and lion (Panthera leo). Anthrax deaths were highest in the rainy season for zebra, wildebeest and springbok, while elephant mortality peaked during dry seasons. No statistical relationship existed between seasonal rainfall and overall incidence of either anthrax or rabies. Control of anthrax is limited to prophylactic inoculation when rare or endangered species are threatened. Incineration of anthrax carcasses and chemical disinfection of drinking water are not feasible at Etosha. Rabies control consists of the destruction of rabid animals and incineration of their carcasses when possible.

Animals↗
PubMed2005

Demand for prophylaxis after bioterrorism-related anthrax cases, 2001.

Media reports suggested increased public demand for anthrax prophylaxis after the intentional anthrax cases in 2001, but the magnitude of anthrax-related prescribing in unaffected regions was not assessed. We surveyed a random sample of 400 primary care clinicians in Minnesota and Wisconsin to assess requests for and provision of anthrax-related antimicrobial agents. The survey was returned by 239 (60%) of clinicians, including 210 in outpatient practice. Fifty-eight (28%) of those in outpatient practice received requests for anthrax-related antimicrobial agents, and 9 (4%) dispensed them. Outpatient fluoroquinolone use in both states was also analyzed with regression models to compare predicted and actual use in October and November 2001. Fluoroquinolone use as a proportion of total antimicrobial use was not elevated, and anthrax concerns accounted for an estimated 0.3% of all fluoroquinolone prescriptions. Most physicians in Minnesota and Wisconsin managed anthrax-related requests without dispensing antimicrobial agents.

Anthrax↗
PubMed2005

Analysis of anthrax and plague biowarfare vaccine interactions with human monocyte-derived dendritic cells.

The anti-biowarfare anthrax and plague vaccines require repeated dosing to achieve adequate protection. To test the hypothesis that this limited immunogenicity results from the nature of vaccine interactions with the host innate immune system, we investigated molecular and cellular interactions between vaccines, dendritic cells (DCs), and T cells and explored the potential for adjuvants (pertussis) to boost induction of host immunity. Human monocyte-derived DCs were matured in the presence of vaccines and analyzed for their ability to induce Th1/Th2 development from naive T cells, expression of cell surface maturation/costimulation molecules, and cytokine production. The vaccines showed different behavior patterns. Although the plague vaccine is equivalent to control maturation factors in maturation and stimulation of DCs and induces strong MLR and Th outgrowth, the anthrax vaccine is a poor inducer of DC maturation, as indicated by low levels of HLA-DR, CD86, and CD83 induction and minimal proinflammatory cytokine production. Interestingly, however, anthrax vaccine-treated DCs stimulate Th1 and Th2 outgrowth and a limited MLR response. There was no sustained negative modulatory effects of the anthrax vaccine on DCs, and its limited stimulatory effects could be overridden by coculture with pertussis. These results were supported by analysis of anthrax vaccine recall responses in subjects vaccinated using pertussis as an adjuvant, who demonstrate anthrax-specific effector T cell responses. These data show that the anthrax vaccine is a suboptimal DC stimulus that may in part explain the observation that it requires repeated administration in vivo and offer a rational basis for the use of complementary DC-maturing adjuvants in combined immunotherapy.

Adjuvants, Immunologic↗