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PubMed2004

The hybrid cytomegalovirus enhancer/chicken beta-actin promoter along with woodchuck hepatitis virus posttranscriptional regulatory element enhances the protective efficacy of DNA vaccines.

DNA vaccines represent a novel and powerful alternative to conventional vaccine approaches. They are extremely stable and can be produced en masse at low cost; more importantly, DNA vaccines against emerging pathogens or bioterrorism threats can be quickly constructed based solely upon the pathogen's genetic code. The main drawback of DNA vaccines is that they often induce lower immune responses than traditional vaccines, particularly in nonrodent species. Thus, improving the efficacy of DNA vaccines is a critical issue in vaccine development. In this study we have enhanced the efficacy of DNA vaccines by adopting strategies that increase gene expression. We generated influenza-hemagglutinin (HA)-encoding DNA vaccines that contain the hybrid CMV enhancer/chicken beta-actin (CAG) promoter and/or the mRNA-stabilizing post-transcriptional regulatory element from the woodchuck hepatitis virus (WPRE). Mice were immunized with these DNA vaccines, and the influenza-HA-specific cellular and humoral immune responses were compared with a conventional, HA-encoding DNA vaccine whose gene expression was driven by the CMV immediate-early promoter (pCMV-HA). CAG promoter-driven DNA vaccines elicited significantly higher humoral and cellular immune responses compared with the pCMV-HA vaccine. DNA vaccines consisting of both CAG and WPRE elements (pCAG-HA-WPRE) induced the highest level of protective immunity, such that immunization with 10-fold lower DNA doses prevented death in 100% of the mice upon lethal viral challenge, whereas all mice immunized with the conventional pCMV-HA vaccine succumbed to influenza infection.

Actins↗

PubMed2005

A novel neurotoxoid vaccine prevents mucosal botulism.

The threat posed by botulism, classically a food- and waterborne disease with a high morbidity and mortality, has increased exponentially in an age of bioterrorism. Because botulinum neurotoxin (BoNT) could be easily disseminated by terrorists using an aerosol or could be used to contaminate the food or water supply, the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases has classified it as a category A agent. Although clearly the development of a safe and effective mucosal vaccine against this toxin should be a high priority, essentially no studies to date have assessed mucosal immune responses to this disease. To bridge this gap in our knowledge, we immunized mice weekly for 4 wk with nasal doses of BoNT type A toxoid and a mutant of cholera toxin termed E112K. We found elevated levels of BoNT-specific IgG Abs in plasma and of secretory IgA Abs in external secretions (nasal washes, saliva, and fecal extracts). When mice given nasal BoNT vaccine were challenged with 4 x 10(3) LD50 of BoNT type A (BoNT/A) via the i.p. route, complete protection was seen, while naive mice given the same dosage died within 2 h. To further confirm the efficacy of this nasal BoNT vaccine, an oral LD50 was determined. When mice were given an oral challenge of 5 microg (2 x oral LD50) of progenitor BoNT/A, all immunized mice survived beyond 5 days, while nonimmunized mice did not. The fecal extract samples from nasally vaccinated mice were found to contain neutralizing secretory IgA Abs. Taken together, these results show that nasal BoNT/A vaccine effectively prevents mucosal BoNT intoxication.

Adjuvants, Immunologic↗

PubMed2006

Cyclooxygenase-2 inhibition attenuates antibody responses against human papillomavirus-like particles.

Vaccination to generate protective humoral immunity against infectious disease is becoming increasingly important due to emerging strains of virus, poorly immunogenic vaccines, and the threat of bioterrorism. We demonstrate that cyclooxygenase-2 (Cox-2) is crucial for optimal Ab responses to a model vaccine, human papillomavirus type 16 virus-like particles (HPV 16 VLPs). Cox-2-deficient mice produce 70% less IgG, 50% fewer Ab-secreting cells, and 10-fold less neutralizing Ab to HPV 16 VLP vaccination compared with wild-type mice. The reduction in Ab production by Cox-2(-/-) mice was partially due to a decrease in class switching. SC-58125, a structural analog of the Cox-2-selective inhibitor Celebrex reduced by approximately 70% human memory B cell differentiation to HPV 16 VLP IgG-secreting cells. The widespread use of nonsteroidal anti-inflammatory drugs and Cox-2-selective inhibitory drugs may therefore reduce vaccine efficacy, especially when vaccines are poorly immunogenic or the target population is poorly responsive to immunization.

Animals↗

PubMed2006

States' emergency orders regarding the 2004-05 influenza vaccine shortage.

Influenza vaccine shortages during the 2004-05 season led some states to issue emergency orders that prioritized high-risk groups and in some cases threatened criminal penalties. Decision-making that led states to issue - or not issue - these orders has not been examined. Therefore, we conducted analyses of semi-structured, in-depth interviews with health officials in 23 states, in order to identify principal decision-making factors and patterns regarding emergency flu vaccine orders. Four of 14 issuing states and one of 9 non-issuing states had a formal structure for decisions of this nature; 3 states utilized a bioterrorism preparedness infrastructure. Eight issuing states cited inadequate or uncertain supply as most important in their decision-making. Four issuing states said that informing the public that high-risk prioritization was a state decision (and not a provider-specific decision) was most important. Among non-issuing states, 7/9 believed they could accomplish their objectives without issuing an order. No states had formal mechanisms to assess vaccine supply or monitor physicians' adherence to prioritization guidelines. We conclude that broad differences in states' approaches to influenza vaccine supply illustrate 3 salient themes: decentralization of vaccine supply control and management, lack of monitoring and enforcement capacity, and benefits of disaster preparedness efforts.

Centers for Disease Control and Prevention, U.S.↗

PubMed2006

National surveillance and the epidemiology of human Q fever in the United States, 1978-2004.

Although Q fever is considered enzootic in the United States, surveillance for human Q fever has been historically limited. From 1978 through 1999, 436 cases (average = 20 per year) of human Q fever were reported. After Q fever became nationally reportable in 1999, 255 human Q fever cases (average = 51 per year) were reported with illness onset during 2000 through 2004. The median age of cases was 51 years, and most cases were male (77%). The average annual incidence of Q fever was 0.28 cases per million persons, and was highest in persons 50-59 years of age (0.39 cases per million). State-specific incidence ranged from a high of 2.40 cases per million persons in Wyoming, to 0 cases in some states. Since Q fever became reportable, case reports have increased by more than 250%. Surveillance for Q fever is essential to establish the distribution and magnitude of disease and to complement U.S. bioterrorism preparedness activities.

Adolescent↗

PubMed2006

Planning for avian influenza.

Avian influenza, or influenza A (H5N1), has 3 of the 4 properties necessary to cause a serious pandemic: It can infect people, nearly all people are immunologically naive, and it is highly lethal. The Achilles heel of the virus is the lack of sustained human-human transmission. Fortunately, among the 124 cases reported through 30 May 2006, nearly all were acquired by direct contact with poultry. Unfortunately, the capability for efficient human-human transmission requires only a single mutation by a virus that is notoriously genetically unstable, hence the need for a new vaccine each year for seasonal influenza. Influenza A (H5N1) is being compared to another avian strain, the agent of the "Spanish flu" of 1918-1919, which traversed the world in 3 months and caused an estimated 50 million deaths. The question is, are we ready for this type of pandemic? The answer is probably no. The main problems are the lack of an effective vaccine, very poor surge capacity, a health care system that could not accommodate even a modest pandemic, and erratic regional planning. It's time to get ready, and in the process be ready for bioterrorism, natural disasters, and epidemics of other infectious diseases.

Antiviral Agents↗

PubMedDate not supplied

Emerging infectious diseases in Alaska and the Arctic: a review and a strategy for the 21st century.

Emergence of new, previously unknown, and drug-resistant infectious diseases pose a major threat to global health. The emergence of infectious diseases in Alaska and the Arctic parallels the resurgence of infectious diseases worldwide. The Centers for Disease Control and Prevention has developed a strategy to revitalize the capacity to protect the public from emerging infectious diseases by improving four major public health activities: surveillance and response, applied research, infrastructure and training, and prevention and control. The plan targets high-priority emerging infectious disease problems and particular groups of people at increased risk. These target areas encompass a number of diseases of special concern in Alaska, such as drug-resistant Streptococcus pneumoniae infections, foodborne botulism, alveolar hydatid disease, viral hepatitis, Helicobacter pylori infections, Haemophilus influenzae type b bacteremia and meningitis, and infections of immunocompromised persons, pregnant women and newborns, and tourists. To address these and other emerging infectious disease issues, including the threat of bioterrorism in Alaska and the Arctic, future issues of Alaska Medicine will include updates on specific emerging infectious diseases for health care providers, clinical laboratory workers, and community public health professionals who form the front lines for recognizing, treating, and preventing emerging infectious diseases.

Alaska↗

PubMed2000

The state of public health laboratories.

Public health laboratories in the United States exist at the federal, state, and local level. The earliest laboratories were created in the late 1800s in the wake of the work of Robert Koch and Louis Pasteur. Currently, these laboratories make up a loosely formed network. The combined state portion of this network employs more than 6,000 staff members, tests more than 20 million specimens each year, and has a combined annual budget of more than $300 million. Public health laboratories are found in a variety of organizational settings. Several efforts have been made to define the roles of public health laboratories. Recently, the Association of Public Health Laboratories adopted a consensus position that has formally set forth the core functions, which include activities such as environmental testing, emergency response, surveillance, and reference services. Public health laboratories are being challenged with funding, new technology, and current issues such as bioterrorism, food safety, and antimicrobial resistance.

Communicable Diseases↗

PubMedDate not supplied

Public health infrastructure: creating a solid foundation.

The nation's public health system remains in disarray, despite the 1988 warning by the Institute of Medicine in its landmark report, "The Future of Public Health." Recent concerns about antibiotic resistance, inadequate disease surveillance capabilities, bioterrorism, and an increasing need for training the public health workforce have brought this problem into the forefront of congressional concern. Recent legislation aimed at addressing this problem was passed last Fall and signed into law. This program will take a significant step towards ensuring a solid public health system when it is fully implemented.

Communicable Disease Control↗

PubMed2001

The laboratory role in diagnosis of infections transmitted by arthropods.

This article provides an overview of arbovirus diseases from the perspective of laboratory diagnosis and related responsibilities of health personnel. Although the disease manifestations are very diverse, general lessons relevant to optimal use of laboratory resources can be drawn from medically important examples. This approach is warranted, because under conditions of bioterrorism or emergence of a novel pathogen, ecologic clues that ordinarily facilitate identification of an arbovirus infection most likely will be absent.

Animals↗

PubMed2001

Toxins as weapons of mass destruction. A comparison and contrast with biological-warfare and chemical-warfare agents.

Toxins are toxic chemical compounds synthesized in nature by living organisms. Classifiable by molecular weight, source, preferred targets in the body, and mechanism of action, they include the most potent poisons on the planet, although considerations of production, weaponization, delivery, environmental stability, and host factors place practical limits on their use as WMD. The two most important toxin threats on the battlefield or in bioterrorism are probably botulinum toxin (a series of seven serotypes, of which botulinum toxin A is the most toxic for humans) and SEB, an incapacitating toxin. Ricin and the trichothecene mycotoxins, including T-2 mycotoxin, are of lesser concern but are still potential threats. Botulinum toxin is a neurotoxin, ricin and trichothecene mycotoxins are membrane-damaging proteins, and SEB is a superantigen capable of massive nonspecific activation of the immune system. The clinical intoxications resulting from exposure to and absorption (usually by inhalation) of these agents reflect their underlying pathophysiology. Because of the hybrid nature of toxins, they have sometimes been considered CW agents and sometimes BW agents. The current trend seems to be to emphasize their similarities to living organisms and their differences from CW agents, but examination of all three groups relative to a number of factors reveals both similarities and differences between toxins and each of the other two categories of non-nuclear unconventional WMD. The perspective that groups toxins with BW agents is logical and very useful for research and development and for administrative and treaty applications, but for medical education and casualty assessment, there are real advantages in clinician use of assessment techniques that emphasize the physicochemical behavior of these nonliving, nonreplicating, intransmissible chemical poisons.

Biological Warfare↗

PubMed2002

Cutaneous anthrax: a concise review.

With the growing threat of bioterrorism, it has become important for clinicians to recognize the clinical manifestations of diseases spread in this manner. The aim of this article is to provide readers with a complete and detailed understanding of anthrax, with a specific concentration on the cutaneous manifestations and a concentrated review of the treatment and current information known about Bacillus anthracis.

Administration, Oral↗

PubMed2002

Tularemia--United States, 1990-2000.

Tularemia is a zoonotic disease caused by the gram-negative coccobacillus Francisella tularensis. Known also as "rabbit fever" and "deer fly fever," tularemia was first described in the United States in 1911 and has been reported from all states except Hawaii. Tularemia was removed from the list of nationally notifiable diseases in 1994, but increased concern about potential use of F. tularensis as a biological weapon led to its reinstatement in 2000. This report summarizes tularemia cases reported to CDC during 1990-2000, which indicate a low level of natural transmission. Understanding the epidemiology of tularemia in the United States enables clinicians and public health practitioners to recognize unusual patterns of disease occurrence that might signal an outbreak or a bioterrorism event.

Humans↗

PubMed2002

Oklahoma City and Tulsa Metropolitan Medical Response System.

The tragic loss of lives on September 11 followed by the Anthrax contaminations reinforced the need for work already underway through the Metropolitan Medical Response System (MMRS). Through leadership from the Medical Director for the Medical Control Board and EMSA, Oklahoma City and Tulsa have been the beneficiaries of nearly $1.5 million dollars in funding to prepare for nuclear, chemical or bioterrorism. The two Oklahoma cities were among the second wave of cities invited in 1999 to participate in the federally funded program for Metropolitan Medical Response. Many of the requirements of the contract have already been met under the capable guidance of Michael Murphy, a 23 year paramedic with 12 years of management experience with EMSA. Among the plans completed or underway are a Development Plan, MMRS System Plan, Forward Movement of Patients Plan, Pre-hospital Response Plan, a Biological Incident Plan, a Hospital Response Plan, a Training Plan and an Equipment and Pharmaceutical Plan. Coordinated planning between the two cities bring the added benefit of seamless sharing of personnel between both ends of the turnpike should a disaster impact one rather than both communities.

Civil Defense↗

PubMedDate not supplied

Enterprise digital assistants: the progression of wireless clinical computing.

By virtue of increasingly pervasive wireless connectivity, the proliferation of wireless handheld devices in clinical care is rapidly transforming the concept of the personal digital assistant (PDA) to the enterprise digital assistant (EDA). Wireless handheld devices are becoming extensions of the central hospital information system, in which it's understood that the health care enterprise, not the clinician carrying the information-dispensing device, owns the data. The practical implication for clinicians is that, despite the potential long-term benefits of seamless, just-in-time clinical data access, this paradigm shift portends decreased efficiency in the short term, as clinicians duplicate clinical data collection on private devices. Assuming eventual clinician acceptance, EDAs can form the basis of a national real-time clinical data acquisition system that ensures uniform prescribing, decision support, and diagnosis, and the means for tracking unusual disease presentation patterns that could be indicative of bioterrorism or natural disease outbreaks.

Computer Communication Networks↗

PubMedDate not supplied

Human brucellosis.

BACKGROUND: Human brucellosis has a serious medical impact worldwide, and its eradication poses major difficulties. Although human brucellosis is relatively rare in the United States (approximately 100 cases per year), there is concern that this disease is largely underdiagnosed and underreported. Additionally, immigrants from endemic areas are arriving to this country, and Brucella species are considered to be biologic agents for terrorism. Human brucellosis affects all age-groups, and family physicians are not well versed in recognizing and treating this potentially life-threatening condition. METHODS: A literature review from 1975 to 2001 was performed using the key words "human brucellosis," "zoonosis," and "bioterrorism." RESULTS AND CONCLUSIONS: Appropriate antimicrobial therapy and duration of treatment of human brucellosis will reduce morbidity, prevent complications, and diminish relapses. Because of the nonspecific symptoms and rarity of human brucellosis in the United States, family physicians must acquire a detailed dietary and occupational history to diagnose the disease promptly. Family physicians must assume a responsible role in reporting this disease, as well as be aware of persons at high-risk for this disease and the potential sources of infection.

Anti-Bacterial Agents↗

PubMed2002

Q fever--California, Georgia, Pennsylvania, and Tennessee, 2000-2001.

Q fever is a zoonotic disease caused by the bacterium Coxiella burnetii. The most common reservoirs are domesticated ruminants, primarily cattle, sheep, and goats. Humans acquire Q fever typically by inhaling aerosols or contaminated dusts derived from infected animals or animal products. Its highly infectious nature and aerosol route of transmission make C. burnetii a possible agent of bioterrorism. Although up to 60% of initial infections are asymptomatic, acute disease can manifest as a relatively mild, self-limited febrile illness, or more moderately severe disease characterized by hepatitis or pneumonia. It manifests less commonly as myocarditis, pericarditis, and meningoencephalitis. Chronic Q fever occurs in <1% of infected patients, months or years after initial infection. Chronic disease manifests most commonly as a culture-negative endocarditis in patients with valvular heart disease. During 2000-2001, a total of 48 patients who met the case definition of Q fever were reported to CDC. This report describes the case investigations for six of these patients, which indicate that these persons acquired Q fever probably through direct or indirect contact with livestock. To enhance surveillance efforts, health-care providers should report cases of Q fever to state health departments.

Aged↗

PubMed2002

Timely redistribution of information for epidemiological surveillance and alert: the experience from the French communicable diseases network.

Since 1984 the French Communicable Disease Network (FCDN) collects and analyses epidemiological information obtained online from a team of "Sentinel General Practitioners" (SGPs). It redistributes this information in the form of standardised weekly incidence estimates. These weekly estimates now appear on the Internet and are the basis for issuing alerts of influenza epidemics. We postulate that day to day estimations would be highly desirable to achieve timely detection of the actual onset of the epidemic, a need dramatically underscored by the emergence of bioterrorism. The present paper suggests the feasibility of reconstructing daily epidemiological information using local smoothing with a suitable spline function to obtain short latency alert messages.

Algorithms↗

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