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PubMed2003

Control and prevention of emerging zoonoses.

Emerging and re-emerging zoonoses are zoonotic diseases caused by either totally new or partially new agents or by microorganisms previously known but now occurring in places or in species where the disease was previously unknown. Zoonotic diseases account for the majority of all emerging infectious diseases. Several factors have led to the emergence of these infections, including human demographics, the industrialization of food production, globalization, international travel and commerce, land use, microbial adaptation, and changes and breakdown in public health measures. Several zoonotic agents are also potential agents that could be used as biological weapons. The recent use of anthrax spores in tainted mall in the US underlines our need for preparedness against bioterrorism. Prevention and control of these emerging zoonotic diseases is based on recognition, investigation, and collaboration, the development of advanced diagnosis and surveillance tools, the use of applied epidemiology and molecular biology methods, as well as education, information, communication, and technology transfer.

Animals↗

PubMed2006

Historical perspective and future directions in training of veterinary pathologists with an emphasis on zoo and wildlife species.

This article discusses the history of the field of zoo and wildlife pathology, training opportunities for veterinary students and graduate veterinarians, and current and future job opportunities. The niches occupied by veterinarians in this field and their contributions to animal and human health are also highlighted. The field of zoo and wildlife, or "non-traditional" species, pathology has its roots in comparative anatomy, zoology, wildlife biology, and medical pathology in the mid- to late nineteenth century. The initial emphasis was on comparisons between animal and human diseases or on management of game animals. Veterinarians became increasingly involved during the twentieth century, gradually changing the emphasis to improvement of conservation strategies, captive care, and elucidation of diseases of concern for the animals themselves. Currently there are several zoos and wildlife agencies in the United States employing full-time veterinary pathologists. Private and government diagnostic laboratories, veterinary schools, and other academic institutions in the United States with pathology departments are other employers. The field requires post-DVM training by means of a residency program leading to board certification, graduate school (MS or PhD degrees), or both. Veterinary students can gain valuable experience in the field through externships and, at some schools, through elective courses in the curriculum. Current concerns about ecosystem health, bioterrorism, and the recognition that captive and free-ranging wildlife can serve as sentinel species will increase the demand for veterinary pathologists choosing this very rewarding career path specializing in non-traditional species.

Animals↗

PubMed2002

Passive antibody administration (immediate immunity) as a specific defense against biological weapons.

The potential threat of biological warfare with a specific agent is proportional to the susceptibility of the population to that agent. Preventing disease after exposure to a biological agent is partially a function of the immunity of the exposed individual. The only available countermeasure that can provide immediate immunity against a biological agent is passive antibody. Unlike vaccines, which require time to induce protective immunity and depend on the host's ability to mount an immune response, passive antibody can theoretically confer protection regardless of the immune status of the host. Passive antibody therapy has substantial advantages over antimicrobial agents and other measures for postexposure prophylaxis, including low toxicity and high specific activity. Specific antibodies are active against the major agents of bioterrorism, including anthrax, smallpox, botulinum toxin, tularemia, and plague. This article proposes a biological defense initiative based on developing, producing, and stockpiling specific antibody reagents that can be used to protect the population against biological warfare threats.

Antibodies↗

PubMed2002

Epidemic anthrax in the eighteenth century, the Americas.

Anthrax has been described as a veterinary disease of minor importance to clinical medicine, causing occasional occupational infections in single cases or clusters. Its potential for rapid and widespread epidemic transmission under natural circumstances has not been widely appreciated. A little-known 1770 epidemic that killed 15,000 people in Saint-Domingue (modern Haiti) was probably intestinal anthrax. The epidemic spread rapidly throughout the colony in association with consumption of uncooked beef. Large-scale, highly fatal epidemics of anthrax may occur under unusual but natural circumstances. Historical information may not only provide important clues about epidemic development but may also raise awareness about bioterrorism potential.

Animals↗

PubMed2002

Epidemiologic response to anthrax outbreaks: field investigations, 1950-2001.

We used unpublished reports, published manuscripts, and communication with investigators to identify and summarize 49 anthrax-related epidemiologic field investigations conducted by the Centers for Disease Control and Prevention from 1950 to August 2001. Of 41 investigations in which Bacillus anthracis caused human or animal disease, 24 were in agricultural settings, 11 in textile mills, and 6 in other settings. Among the other investigations, two focused on building decontamination, one was a response to bioterrorism threats, and five involved other causes. Knowledge gained in these investigations helped guide the public health response to the October 2001 intentional release of B. anthracis, especially by addressing the management of anthrax threats, prevention of occupational anthrax, use of antibiotic prophylaxis in exposed persons, use of vaccination, spread of B. anthracis spores in aerosols, clinical diagnostic and laboratory confirmation methods, techniques for environmental sampling of exposed surfaces, and methods for decontaminating buildings.

Animals↗

PubMed2002

Environmental sampling for spores of Bacillus anthracis.

On November 11, 2001, following the bioterrorism-related anthrax attacks, the U.S. Postal Service collected samples at the Southern Connecticut Processing and Distribution Center; all samples were negative for Bacillus anthracis. After a patient in Connecticut died from inhalational anthrax on November 19, the center was sampled again on November 21 and 25 by using dry and wet swabs. All samples were again negative for B. anthracis. On November 28, guided by information from epidemiologic investigation, we sampled the site extensively with wet wipes and surface vacuum sock samples (using HEPA vacuum). Of 212 samples, 6 (3%) were positive, including one from a highly contaminated sorter. Subsequently B. anthracis was also detected in mail-sorting bins used for the patient's carrier route. These results suggest cross-contaminated mail as a possible source of anthrax for the inhalational anthrax patient in Connecticut. In future such investigations, extensive sampling guided by epidemiologic data is imperative.

Anthrax↗

PubMed2003

Dead bird clusters as an early warning system for West Nile virus activity.

An early warning system for West Nile virus (WNV) outbreaks could provide a basis for targeted public education and surveillance activities as well as more timely larval and adult mosquito control. We adapted the spatial scan statistic for prospective detection of infectious disease outbreaks, applied the results to data on dead birds reported from New York City in 2000, and reviewed its utility in providing an early warning of WNV activity in 2001. Prospective geographic cluster analysis of dead bird reports may provide early warning of increasing viral activity in birds and mosquitoes, allowing jurisdictions to triage limited mosquito-collection and laboratory resources and more effectively prevent human disease caused by the virus. This adaptation of the scan statistic could also be useful in other infectious disease surveillance systems, including those for bioterrorism.

Animals↗

PubMed2003

Automated, laboratory-based system using the Internet for disease outbreak detection, the Netherlands.

Rapid detection of outbreaks is recognized as crucial for effective control measures and has particular relevance with the recently increased concern about bioterrorism. Automated analysis of electronically collected laboratory data can result in rapid detection of widespread outbreaks or outbreaks of pathogens with common signs and symptoms. In the Netherlands, an automated outbreak detection system for all types of pathogens has been developed within an existing electronic laboratory-based surveillance system called ISIS. Features include the use of a flexible algorithm for daily analysis of data and presentation of signals on the Internet for interpretation by health professionals. By 2006, the outbreak detection system will analyze laboratory-reported data on all pathogens and will cover 35% of the Dutch population.

Algorithms↗

PubMed2003

Flow cytometry and T-cell response monitoring after smallpox vaccination.

Orthopoxvirus zoonosis or smallpox as result of bioterrorism or biological warfare represents a risk for epidemic spread. By monitoring T-cell responses by flow cytometry, we observed a recall response after recent vaccination against smallpox. When the high similarity between the orthopoxviruses is considered, this rapid assay that uses vaccinia antigens could identify recently exposures.

Antigens, Viral↗

PubMed2004

Fatal infectious disease surveillance in a medical examiner database.

Increasing infectious disease deaths, the emergence of new infections, and bioterrorism have made surveillance for infectious diseases a public health concern. Medical examiners and coroners certify approximately 20% of all deaths that occur within the United States and can be a key source of information regarding infectious disease deaths. We hypothesized that a computer-assisted search tool (algorithm) could detect infectious disease deaths from a medical examiner database, thereby reducing the time and resources required to perform such surveillance manually. We developed two algorithms, applied them to a medical examiner database, and verified the cases identified against the opinion of a panel of experts. The algorithms detected deaths with infectious components with sensitivities from 67% to 94%, and predictive value positives ranging from 8% to 49%. Algorithms can be useful for surveillance in medical examiner offices that have limited resources or for conducting surveillance across medical examiner jurisdictions.

Algorithms↗

PubMed2004

Airborne infection with Bacillus anthracis--from mills to mail.

The lack of identified exposures in 2 of the 11 cases of bioterrorism-related inhalation anthrax in 2001 raised uncertainty about the infectious dose and transmission of Bacillus anthracis. We used the Wells-Riley mathematical model of airborne infection to estimate 1) the exposure concentrations in postal facilities where cases of inhalation anthrax occurred and 2) the risk for infection in various hypothetical scenarios of exposure to B. anthracis aerosolized from contaminated mail in residential settings. These models suggest that a small number of cases of inhalation anthrax can be expected when large numbers of persons are exposed to low concentrations of B. anthracis. The risk for inhalation anthrax is determined not only by bacillary virulence factors but also by infectious aerosol production and removal rates and by host factors.

Air Microbiology↗

PubMed2005

Coxiella burnetii genotyping.

Coxiella burnetii is a strict intracellular bacterium with potential as a bioterrorism agent. To characterize different isolates of C. burnetii at the molecular level, we performed multispacer sequence typing (MST). MST is based on intergenic region sequencing. These regions are potentially variable since they are subject to lower selection pressure than the adjacent genes. We screened 68 spacers in 14 isolates and selected the 10 that exhibited the most variation. These spacers were then tested in 159 additional isolates obtained from different geographic areas or different hosts or were implicated in different manifestations of human disease caused by C. burnetii. The sequence analysis yielded 30 different allelic combinations. Phylogenic analysis showed 3 major clusters. MST allows easy comparison and exchange of results obtained in different laboratories and could be a useful tool for identifying bacterial strains.

Base Sequence↗

PubMed2006

Identifying and quantifying genotypes in polyclonal infections due to single species.

Simultaneous infection with multiple pathogens of the same species occurs with HIV, hepatitis C, Epstein-Barr virus, dengue, tuberculosis, and malaria. However, available methods do not distinguish among or quantify pathogen genotypes in individual patients; they also cannot test for novel insertions and deletions in genetically modified organisms. The strategy reported here accomplishes these goals with real-time polymerase chain reaction (PCR) and capillary electrophoresis. Real-time PCR with allotype-specific primers defines the allotypes (strains) present and the intensity of infection (copy number). Capillary electrophoresis defines the number of genotypes within each allotype and the intensity of infection by genotype. This strategy can be used to study the epidemiology of emerging infectious diseases with simultaneous infection by multiple genotypes, as demonstrated here with malaria. It also permits testing for insertions or deletions in genetically modified organisms that may be used for bioterrorism.

Adolescent↗

PubMed2006

Rickettsia prowazekii and real-time polymerase chain reaction.

Rickettsia prowazekii is the causative agent of epidemic typhus and a potential bioterrorism agent. Sensitive and specific rapid assays are needed to complement existing methods of detecting this organism. We developed a real-time quantitative polymerase chain reaction assay by using a species-specific probe targeting the gltA gene. This assay, which was rapid, specific for R. prowazekii only, and sensitive (cutoff detection of 1 to 5 copies per sample), detected and directly identified R. prowazekii in blood of 12 experimentally infected mice sampled at day 3 and 6 postinfection or in naturally or experimentally infected lice. Because our assay is highly standardized and easily adaptable, it could improve epidemic typhus surveillance in public health programs, especially for countries with underdiagnosed or unrecognized human cases.

Animals↗

PubMed1999

The medical impact of a bioterrorist attack. Is it all media hype or clearly a potential nightmare?

Even with the technologic sophistication available in the United States today, effectiveness in dealing with a bioterrorist event is limited. Current surveillance systems may be inadequate to detect attacks. Because the onset of illness after exposure to an agent is delayed, even the time and location of the attack may be vague. In addition, most of the medical community is unfamiliar with many of the high-threat diseases, so identification of the problem may be further delayed. Many of us who are involved in studying the many aspects of bioterrorism believe that it is not a question of if such an event will occur but rather when, as well as which agent will be used and how extensive the damage will be. Given the enormity of what is possible, we must prepare for a potential nightmare.

Biological Warfare↗

PubMed2002

Defending against viruses in biowarfare. How to respond to smallpox, encephalitides, hemorrhagic fevers.

The threat of bioterrorism with use of viruses is increasing. Smallpox, encephalitis, and hemorrhagic fevers are the most likely diseases to result from viral deployment. It is critical that all healthcare professionals become familiar with the clinical presentation, diagnosis, management, and prevention of these diseases. Awareness and preparedness are instrumental in reducing viral transmission and improving survival of the victims.

Biological Warfare↗

PubMed2003

Francisella tularensis selectively induces proinflammatory changes in endothelial cells.

Naturally acquired infections with Francisella tularensis, the bacterial agent of tularemia, occur infrequently in humans. However, the high infectivity and lethality of the organism in humans raise concerns that it might be exploited as a weapon of bioterrorism. Despite this potential for illicit use, the pathogenesis of tularemia is not well understood. To examine how F. tularensis interacts with cells of its mammalian hosts, we tested the ability of a live vaccine strain (LVS) to induce proinflammatory changes in cultured HUVEC. Living F. tularensis LVS induced HUVEC to express the adhesion molecules VCAM-1 and ICAM-1, but not E-selectin, and to secrete the chemokine CXCL8, but not CCL2. Stimulation of HUVEC by the living bacteria was partially suppressed by polymyxin B, an inhibitor of LPS, but did not require serum, suggesting that F. tularensis LVS does not stimulate endothelium through the serum-dependent pathway that is typically used by LPS from enteric bacteria. In contrast to the living organisms, suspensions of killed F. tularensis LVS acquired the ability to increase endothelial expression of both E-selectin and CCL2. Up-regulation of E-selectin and CCL2 by the killed bacteria was not inhibited by polymyxin B. Exposure of HUVEC to either live or killed F. tularensis LVS for 24 h promoted the transendothelial migration of subsequently added neutrophils. These data indicate that multiple components of F. tularensis LVS induce proinflammatory changes in endothelial cells in an atypical manner that may contribute to the exceptional infectivity and virulence of this pathogen.

Anti-Bacterial Agents↗

PubMed2004

Selective killing of vaccinia virus by LL-37: implications for eczema vaccinatum.

Possible bioterrorism with smallpox has led to the resumption of smallpox (vaccinia virus) immunization. One complication, eczema vaccinatum, occurs primarily in patients with atopic dermatitis (AD). Skin lesions of patients with AD, but not psoriasis, is deficient in the cathelicidin antimicrobial peptide (LL-37) and human beta-defensin-2 (HBD-2). We hypothesized that this defect may explain the susceptibility of patients with AD to eczema vaccinatum. The Wyeth vaccine strain of vaccinia virus was incubated with varying concentrations of human (LL-37) and murine (CRAMP) cathelicidins, human alpha-defensin (HBD-1, HBD-2), and a control peptide. Outcomes included quantification of viral PFU, vaccinia viral gene expression by quantitative real-time RT-PCR, and changes in virion structure by transmission electron microscopy. CRAMP knockout mice and control animals were inoculated by skin pricks with 2 x 10(5) PFU of vaccinia and examined daily for pox development. Physiologic amounts of human and murine cathelicidins (10-50 micro M), but not human defensins, which had antibacterial activity, resulted in the in vitro reduction of vaccinia viral plaque formation (p < 0.0001), vaccinia mRNA expression (p < 0.001), and alteration of vaccinia virion structure. In vivo vaccinia pox formation occurred in four of six CRAMP knockout animals and in only one of 15 control mice (p < 0.01). These data support a role for cathelicidins in the inhibition of orthopox virus (vaccinia) replication both in vitro and in vivo. Susceptibility of patients with AD to eczema vaccinatum may be due to a deficiency of cathelicidin.

Amino Acid Sequence↗