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PubMed2006

Botulinum A toxin for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms.

Botulinum neurotoxin (BoNT) has been called the most poisonous poison and a potential bioterrorism weapon, and yet modern medicine has been able to harvest the elegant and specific activity of this toxin to treat a variety of medical conditions. BoNT application recently has been extended to prostate disorders, and this article reviews the literature on the mechanisms of action and clinical efficacy of BoNT treatment in the prostate. BoNT has demonstrated promising preliminary results for male lower urinary tract symptoms, and translational research suggests novel mechanism of action of BoNT in the prostate. It is important to remember that the application of BoNT in the prostate is not approved by the regulatory agencies and caution should be applied until larger randomized clinical studies are completed.

Botulinum Toxins, Type A↗

PubMed2005

Microencapsulated subunit vaccine approach to enterotoxigenic Escherichia coli and other mucosal pathogens.

Infections of the intestinal, urogenital, and respiratory tracts are serious health problems worldwide from both a morbidity and mortality perspective. Mucosal pathogens attach to surfaces of mucosa as a prerequisite for colonization and subsequent pathogenesis. By expressing various surface adhesins (colonization factors, CF) they are able to bind to specific mucosal receptors. Enterotoxigenic Escherichia coli (ETEC) can express numerous CF that allow them to attach to a variety of hosts. Mucosal immunity directed against pathogenic microorganisms is critical in host protection with secretory IgA being particularly important in preventing microoganisms from colonizing host cells. M cells likewise have an important immunological function in the small intestines by binding and transporting antigens to lymphocytes and macrophages thus enhancing the immune response. The use of subunit vaccines, such as antigen encapsulated microspheres, can act to effectively deliver specific antigens so as to optimize their immunological response. With the threat of bioterrorism becoming a reality in recent years, the miroencapsulation of antigens from potential bioterrorist agents may be an effective method of delivery so as to induce a level of protection in at risk individuals. The encapsulation of ETEC colonization factors in microspheres and their subsequent administration in small animals and humans has been conducted for many years. Evidence suggests that this type of delivery system for ETEC antigens may enhance their immunogenicity and provide protection against this microorganism.

Adhesins, Escherichia coli↗

PubMed2005

Vaccination strategies for Francisella tularensis.

Francisella tularensis is the etiologic agent of tularemia, a severe debilitating disease of humans and animals. The low infectious dose of F. tularensis in humans and the relative ease of culture are probably the properties which originally attracted interest in this bacterium as a bioweapon. Even today, F. tularensis is ranked as one of the pathogens most likely to be used as a biological warfare or bioterrorism agent. A live attenuated vaccine (LVS) has been available for over 50 years, but there are shortcomings associated with its use. This vaccine is not fully licensed and does not offer a high level of protection against respiratory challenge. Nevertheless, this vaccine does demonstrate the feasibility of vaccination against tularemia. Protection against tularemia is likely to be dependent on the induction of cellular and humoral immune responses. These types of responses are induced by the LVS vaccine and could also be induced by a rationally attenuated mutant of F. tularensis. Evoking this range of responses with a sub-unit vaccine may be more difficult to achieve, and will be dependent on the use of suitable vaccine delivery systems.

Animals↗

PubMed2006

Needle-free vaccine delivery.

The search for methods of vaccine delivery not requiring a needle and syringe has been accelerated by recent concerns regarding pandemic disease, bioterrorism, and disease eradication campaigns. Needle-free vaccine delivery could aid in these mass vaccinations by increasing ease and speed of delivery, and by offering improved safety and compliance, decreasing costs, and reducing pain associated with vaccinations. In this article, we summarize the rationale for delivery of needle-free vaccines and discuss several methods currently in use and under development, focusing on needle-free injection devices, transcutaneous immunization, and mucosal immunization. Jet injectors are needle-free devices that deliver liquid vaccine through a nozzle orifice and penetrate the skin with a high-speed narrow stream. They generate improved or equivalent immune responses compared with needle and syringe. Powder injection, a form of jet injection using vaccines in powder form, may obviate the need for the "cold chain." Transcutaneous immunization involves applying vaccine antigen and adjuvant to the skin, using a patch or "microneedles," and can induce both systemic and mucosal immunity. Mucosal immunization has thus far been focused on oral, nasal, and aerosol vaccines. Promising newer technologies in oral vaccination include using attenuated bacteria as vectors and transgenic plant "edible" vaccines. Improved knowledge regarding the immune system and its responses to vaccination continues to inform vaccine technologies for needle-free vaccine delivery.

Administration, Topical↗

PubMed2004

Mass smallpox immunization program in a deployed military setting.

A prospective, observational study of immunizing over 6,000 active-duty troops against smallpox in a 4-week time period was conducted. It focused on the complications of the vaccine and lost workdays. Comparison is made to the complication rates of earlier smallpox immunization programs. In direct response to elevated bioterrorism concerns, the United States military and civilian first-responders have begun a mass smallpox immunization program. This article reviews the experience with implementing such a program in a forward-deployed location while maintaining military readiness. The objectives were to assess the impact of a mass smallpox immunization program on operations in a forward-deployed military setting and to comment on lessons learned in the screening and immunization process. From January 16, 2003 through February 11, 2003 6,002 members of the United States military were immunized in a forward-deployed location. Information was obtained using data from the Air Force Complete Information Tracking Application (AFCITA) and the Global Expeditionary Medical System (GEMS) we plan to calculate the following Main Outcome Measures data: (1)Percentage of individuals eligible to receive the vaccine, (2) Vaccine take rate by CDC criteria, (3) Number of serious complications, (4) Number of life-threatening complications, and (5) Number of manpower days lost as a complication of the vaccine. A total of 6,739 individuals were screened for vaccination with 6,348 (94%) remaining eligible for the vaccine. The "take" rate for the vaccine was 98.6% as per Centers for Disease Control and Prevention (CDC) criteria. The immunization program produced an additional 156 medical visits (2.6% of patients required one visit). A total of 0.55% of immunized individuals lost one or more work days. In conclusion, a mass smallpox vaccination program can be effectively administered in a forward-deployed military setting despite high tempo military operations with minimal operational impact.

Humans↗

PubMed2004

Use of a portable forced air system to convert existing hospital space into a mass casualty isolation area.

STUDY OBJECTIVE: Patients with communicable diseases may require respiratory isolation to reduce the chance of transmission to health care workers and the public. This project was conducted to determine whether negative-pressure isolation for multiple patients can be achieved quickly and effectively using general hospital space not previously dedicated to respiratory isolation. METHODS: The physical therapy gymnasium was the area designated to test the ability to create a negative-pressure isolation environment in a large space. The conversion was planned in advance of an unscheduled drill to convert the space. Four high-efficiency particulate air (HEPA) filtered forced air machines were used to generate negative pressure. The units were vented to the outside air by a 25-foot length of 10-inch-diameter reusable duct. We evaluated the time needed for equipment setup and room conversion and noted any subjective difficulty with either setup or operation of the equipment. We measured the ability of the equipment to generate a negative air pressure relative to adjacent areas and determined the noise levels created during the use of different combinations of machines at various power settings. RESULTS: After drill activation and the request for equipment setup, 1 hour was required to convert the physical therapy gymnasium into an operational negative-pressure environment. The room pressure readings "high" power ranged from -1.5 to -13 Pa (-0.006 to -0.052 inches of water), and noise levels ranged from 70 to 76 dB. Calculated air changes per hour using 1, 2, 3, or 4 units running simultaneously at "high" power were 4.1, 8.2, 12.3, and 16.4, respectively. Using 4 units at once running at "low" power setting yielded 8.2 air changes per hour and generated a room pressure reading of -8.0 Pa, or -0.032 inches of water. CONCLUSION: Portable HEPA filtered forced air units are an effective means of creating large patient care areas with the negative-pressure environment required for respiratory isolation. This design results in a significantly lower-cost alternative compared with construction of individual rooms or units with similar capability and can be retrofitted to existing space. This type of unit would allow treatment of many more patients than current hospital capability would permit and would be an important asset in meeting the needs created by bioterrorism or a naturally occurring epidemic.

Feasibility Studies↗

PubMed2006

Respiratory hygiene in the emergency department.

The emergency department (ED) is an essential component of the public health response plan for control of acute respiratory infectious threats. Effective respiratory hygiene in the ED is imperative to limit the spread of dangerous respiratory pathogens, including influenza, severe acute respiratory syndrome, avian influenza, and bioterrorism agents, particularly given that these agents may not be immediately identifiable. Sustaining effective respiratory control measures is especially challenging in the ED because of patient crowding, inadequate staffing and resources, and ever-increasing numbers of immunocompromised patients. Threat of contagion exists not only for ED patients but also for visitors, health care workers, and inpatient populations. Potential physical sites for respiratory disease transmission extend from out-of-hospital care, to triage, waiting room, ED treatment area, and the hospital at large. This article presents a summary of the most current information available in the literature about respiratory hygiene in the ED, including administrative, patient, and legal issues. Wherever possible, specific recommendations and references to practical information from the Centers for Disease Control and Prevention are provided. The "Administrative Issues" section describes coordination with public health departments, procedures for effective facility planning, and measures for health care worker protection (education, staffing optimization, and vaccination). The patient care section addresses the potentially infected ED patient, including emergency medical services concerns, triage planning, and patient transport. "Legal Issues" discusses the interplay between public safety and patient privacy. Emergency physicians play a critical role in early identification, treatment, and containment of potentially lethal respiratory pathogens. This brief synopsis should help clinicians and administrators understand, develop, and implement appropriate policies and procedures to address respiratory hygiene in the ED.

Emergency Service, Hospital↗

PubMed2004

Crimean-Congo hemorrhagic fever.

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease caused by the arbovirus Crimean-Congo hemorrhagic fever virus (CCHFV), which is a member of the Nairovirus genus (family Bunyaviridae). CCHF was first recognized during a large outbreak among agricultural workers in the mid-1940s in the Crimean peninsula. The disease now occurs sporadically throughout much of Africa, Asia, and Europe and results in an approximately 30% fatality rate. After a short incubation period, CCHF is characterized by a sudden onset of high fever, chills, severe headache, dizziness, back, and abdominal pains. Additional symptoms can include nausea, vomiting, diarrhea, neuropsychiatric, and cardiovascular changes. In severe cases, hemorrhagic manifestations, ranging from petechiae to large areas of ecchymosis, develop. Numerous genera of ixodid ticks serve both as vector and reservoir for CCHFV; however, ticks in the genus Hyalomma are particularly important to the ecology of this virus. In fact, occurrence of CCHF closely approximates the known world distribution of Hyalomma spp. ticks. Therefore, exposure to these ticks represents a major risk factor for contracting disease; however, other important risk factors are known and are discussed in this review. In recent years, major advances in the molecular detection of CCHFV, particularly the use of real-time reverse transcription-polymerase chain reaction (RT-PCR), in clinical and tick samples have allowed for both rapid diagnosis of disease and molecular epidemiology studies. Treatment options for CCHF are limited. Immunotherapy and ribavirin have been tried with varying degrees of success during sporadic outbreaks of disease, but no case-controlled trials have been conducted. Consequently, there is currently no antiviral treatment for CCHF approved by the U.S. Food and Drug Administration (FDA). However, renewed interested in CCHFV, as well as increased knowledge of its basic biology, may lead to improved therapies in the future. This article reviews the history, epidemiology, ecology, clinical features, pathogenesis, diagnosis, and treatment of CCHF. In addition, recent advances in the molecular biology of CCHFV are presented, and issues related to its possible use as a bioterrorism agent are discussed.

Animals↗

PubMed2005

The efficacy of cidofovir treatment of mice infected with ectromelia (mousepox) virus encoding interleukin-4.

Improved vaccines and therapies for virulent poxvirus infection are required, particularly in the light of recent threats of bioterrorism. Cidofovir (HPMPC) is an acyclic nucleoside analog with proven efficacy against poxviruses. Here, we evaluated HPMPC in mice given a recombinant ectromelia virus (ECTV) encoding interleukin-4 (ECTV-IL-4) that is highly immune suppressive. Mousepox-sensitive BALB/c mice given HPMPC for five consecutive days after infection were protected against the lethal effects of a control ECTV recombinant, although they suffered a chronic form of mousepox disease. High doses of the drug resulted in a milder localized disease. In contrast, HPMPC failed to protect mousepox-resistant C57BL/6 mice against ECTV-IL-4, although its lethal effects were delayed by five daily doses of 20 mg/kg or a single dose of 100 mg/kg. Higher daily doses further delayed mortality, although the majority of animals eventually succumbed to infection. It appears that HPMPC inhibited ECTV-IL-4 replication without clearance, with the virus having a lethal effect when the drug was removed. Resistance of ECTV-IL-4 to HPMPC treatment may relate to the virus's ability to inhibit antiviral cell-mediated immunity. Interestingly, ECTV-IL-4-mediated immune suppression was not accompanied by a reduction in systemic IFN-gamma expression, suggestive of an alternative or highly localized suppressive mechanism.

Animals↗

PubMed2004

Impact of a viral respiratory epidemic on the practice of medicine and rehabilitation: severe acute respiratory syndrome.

Severe acute respiratory syndrome (SARS) is a new respiratory viral epidemic that originated in China but has affected many parts of the world, with devastating impact on economies and the practice of medicine and rehabilitation. A novel coronavirus has been implicated, with transmission through respiratory droplets. Rehabilitation was significantly affected by SARS, because strict infection control measures run counter to principles such as multidisciplinary interactions, patients encouraging and learning from each other, and close physical contact during therapy. Immunocompromised patients who may silently carry SARS are common in rehabilitation and include those with renal failure, diabetes, and cancer. Routine procedures such as management of feces and respiratory secretions (eg, airway suctioning, tracheotomy care) have been classified as high risk. Personal protection equipment presented not only a physical but also a psychologic barrier to therapeutic human contact. Visitor restriction to decrease chances of disease transmission are particularly difficult for long-staying rehabilitation patients. At the height of the epidemic, curtailment of patient movement stopped all transfers for rehabilitation, and physiatrists had to function as general internists. Our experiences strongly suggest that rehabilitation institutions should have emergency preparedness plans because such epidemics may recur, whether as a result of nature or of bioterrorism.

Communicable Diseases, Emerging↗

PubMed2004

Smallpox in the 21st century.

The viral disease, smallpox, was well known through the end of the 20th Century. Because it has been eradicated from natural populations, the present clinical experience with managing the disease is limited. Similarly, research in the pathophysiology, treatment, and prevention of the disease has recently become a priority. Concerns regarding smallpox as a weapon of bioterrorism have led to the implementation of a new prophylactic vaccine program, a renewal in variola vaccine research, and treatment regimens against variola infection.

Humans↗

PubMed2005

A national curriculum for nurses in emergency preparedness and response.

Preliminary and continuing education concerning emergency preparedness is needed for nurses. Although some nurses have had natural disaster training, most have not had training to respond to bioterrorism events. Several organizations are working to develop standards and curricula for such training. This article highlights these efforts.

Curriculum↗

PubMed2004

Detection and enumeration of airborne biocontaminants.

The sampling and analysis of airborne microorganisms has received attention in recent years owing to concerns with mold contamination in indoor environments and the threat of bioterrorism. Traditionally, the detection and enumeration of airborne microorganisms has been conducted using light microscopy and/or culture-based methods; however, these analyses are time-consuming, laborious, subjective and lack sensitivity and specificity. The use of molecular methods, such as quantitative polymerase chain reaction amplification, can enhance monitoring strategies by increasing sensitivity and specificity, while decreasing the time required for analysis.

Aerosols↗

PubMed2004

Smallpox: vaccine reactions and contraindications.

Concern regarding the use of smallpox for bioterrorism has led to the reintroduction of smallpox vaccination. The historic background leading to protective methods against smallpox disease, the adverse reactions and contraindications associated with vaccination, and the ongoing development of potentially safer smallpox vaccines are reviewed here.

Adolescent↗

PubMed2004

Tularemia: the disease and the weapon.

Tularemia is a bacterial infection usually transmitted via arthropod vectors or direct contact with infected animals. Naturally occurring cases are relatively rare, and can result in six different clinical syndromes. Tularemia is also a potential agent of bioterrorism or biowarfare, and is categorized as a high-level threat. Effective antibiotic treatment is available, including potential use of oral antibiotics in a mass casualty situation. An awareness of potential clinical presentations of tularemia will facilitate timely intervention,appropriate diagnostic testing, and decreased morbidity in the event of a biologic attack with Francisella tularensis.

Animals↗

PubMed2006

Emergency medicine and the public's health: emerging infectious diseases.

In recent years, multiple global forces have contributed to the emergence and widespread distribution of previously unknown disease entities. This article discusses Ebola virus, West Nile virus, and Hantavirus as representative emerging infectious diseases. Smallpox is discussed along with concerns about the safety of the smallpox vaccine, given the uncertain risk of bioterrorism and smallpox exposure. ED physicians must become familiar with the presentation, management, and public health impact of all of these entities, as well as understand the potential impact of other emerging infectious diseases.

Adult↗

PubMed2004

Genome diversity among regional populations of Francisella tularensis subspecies tularensis and Francisella tularensis subspecies holarctica isolated from the US.

Francisella tularensis is a highly infectious facultative intracellular pathogen that is considered a potential agent of bioterrorism. Four different F. tularensis subspecies have been identified and they appear to display different ecological and virulence characteristics as well as differences in geographical distribution. One simple explanation for the variation in ecological and virulence characteristics is that they are conferred by differences in genome content. To characterize genome content among stains isolated from United States, we have used a DNA microarray designed from a shotgun library of a reference strain. Polymorphisms distributed among polyphyletic sets of strains was the most common pattern of genome alteration observed, indicating that strain-specific genome variability is significant. Nonetheless, 13 different contiguous segments of the genome were found to be missing exclusively in each of the subsp. holarctica strains tested. All 13 are associated with repeat sequences or transposases that could promote insertion/deletion events. Comparison of the live vaccine strain to other holarctica strains also identified three regions that are absent exclusively in the live vaccine strain derived from holarctica.

Bacterial Vaccines↗

PubMed2005

Role of superoxide in the germination of Bacillus anthracis endospores.

The spore forming Gram-positive bacterium Bacillus anthracis, the causative agent of anthrax, has achieved notoriety due to its use as a bioterror agent. In the environment, B. anthracis exists as a dormant endospore. Germination of endospores during their internalization within the myeloid phagocyte, and the ability of those endospores to survive exposure to antibacterial killing mechanisms such as superoxide (O(2)*-, is a key initial event in the infective process. We report herein that endospores exposed to fluxes of O(2)*- typically found in stimulated phagocytes had no effect on viability. Further endospores of the Sterne strain of B. anthracis were found to scavenge O(2)*-, which may enhance the ability of the bacterium to survive within the hostile environment of the phagolysosome. Most intriguing was the observation that endospore germination was stimulated by a flux of O(2)*- as low as 1 microM/min. Data presented herein suggest that B. anthracis may co-opt O(2)*- which is produced by stimulated myeloid phagocytes and is an essential element of host immunity, as a necessary step in productive infection of the host.

Bacillus anthracis↗