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PubMed2004

Chickenpox or smallpox: the use of the febrile prodrome as a distinguishing characteristic.

BACKGROUND: The ability to differentiate chickenpox from smallpox is important for early recognition of bioterrorism events and prevention of false alarms. The febrile prodrome is a clinical feature used to differentiate these conditions. However, the prevalence of prodromal manifestations in chickenpox has not been well established. METHODS: We evaluated prodrome characteristics of all chickenpox cases identified through an active varicella surveillance program over a 21-month period. The frequencies of various prodromal manifestations among vaccinated and unvaccinated case patients were assessed, and the impact of other demographic features on these manifestations was evaluated. Data were analyzed to determine what proportion met the smallpox febrile prodrome criteria as elaborated in the Centers for Disease Control and Prevention algorithm for evaluating patients suspected of having smallpox. Finally, we compared our data with historical data on smallpox prodromes. RESULTS: Data on prodrome characteristics were available for 932 chickenpox cases. Prodromal fever was present in 37% of unvaccinated chickenpox case patients and in 25% of vaccinated case patients. Among unvaccinated case patients, adults were 70% more likely than children to have fever in the prodrome period. We found that prodromes are less common and less severe in chickenpox than in smallpox. Nevertheless, 7%-17% of unvaccinated chickenpox case patients meet the smallpox febrile prodrome criteria. CONCLUSIONS: Febrile prodromes occur in a significant proportion of patients with chickenpox, particularly among unvaccinated case patients and adults. Therefore, the febrile prodrome alone is not a sufficient marker of smallpox risk. All major and minor smallpox criteria should be considered together in assessing the likelihood of smallpox.

Adolescent↗

PubMed2005

Reemergence of monkeypox: prevalence, diagnostics, and countermeasures.

Human monkeypox is a viral zoonotic disease that occurs mostly in the rain forests of central and western Africa. However, the disease recently emerged in the United States in imported wild rodents from Africa. Monkeypox has a clinical presentation very similar to that of ordinary forms of smallpox, including flulike symptoms, fever, malaise, back pain, headache, and characteristic rash. Given this clinical spectrum, differential diagnosis to rule out smallpox is very important. There are no licensed therapies for human monkeypox; however, the smallpox vaccine can protect against the disease. The discontinuation of general vaccination in the 1980s has given rise to increasing susceptibility to monkeypox virus infection in the human population. This has led to fears that monkeypox virus could be used as a bioterrorism agent. Effective prevention relies on limiting the contact with infected patients or animals and limiting the respiratory exposure to infected patients.

Animals↗

PubMed2000

The threat of biological terrorism: a public health and infection control reality.

Bioterrorism is an emerging public health and infection control threat. Potential biological agents include smallpox, anthrax, plague, tularemia, botulinum toxin, brucellosis, Q fever, viral encephalitis, hemorrhagic fever, and staphylococcal enterotoxin B. An understanding of the epidemiology, clinical manifestations, and management of the more likely candidate agents is critical to limiting morbidity and mortality from a biological event. Effective response requires an increased index of suspicion for unusual diseases or syndromes, with prompt reporting to health authorities to facilitate recognition of an outbreak and subsequent intervention. Hospital epidemiology programs will play a crucial role in this effort.

Anthrax↗

PubMed2006

VisualDx: decision-support software for the diagnosis and management of dermatologic disorders.

The VisualDx system (http://www.logicalimages.com/prodVDx.htm) is a JAVA-based decision-support program developed by Logical Images to be used in clinical care to develop differential diagnoses based upon morphologic finding- and patient finding-driven searching. It consists of several modules, many of which are very relevant to infectious diseases specialists, such as Fever & Rash; International Travel; Drug Eruptions; Smallpox Vaccination; Terrorism Recognition; Immunocompromised, HIV or AIDS; Female Genital Rashes & Growths; and Male Genital Rashes & Growths. Unlike books and atlases indexed by disease, with VisualDx, clinicians can enter patient descriptors and lesion morphologies, resulting in rapid assistance with differential diagnosis. VisualDx also increases clinician awareness of, knowledge about, and skills in the recognition of chemical warfare, bioterrorism, and radiation injuries.

Decision Making, Computer-Assisted↗

PubMed2004

Natural histories of infectious disease: ecological vision in twentieth-century biomedical science.

During the twentieth century, disease ecology emerged as a distinct disciplinary network within infectious diseases research. The key figures were Theobald Smith, F. Macfarlane Burnet, René Dubos, and Frank Fenner. They all drew on Darwinian evolutionism to fashion an integrative (but rarely holistic) understanding of disease processes, distinguishing themselves from reductionist "chemists" and mere "microbe hunters." They sought a more complex, biologically informed epidemiology. Their emphasis on competition and mutualism in the animated environment differed from the physical determinism that prevailed in much medical geography and environmental health research. Disease ecology derived in part from studies of the interaction of organisms - micro and macro - in tropical medicine, veterinary pathology, and immunology. It developed in postcolonial settler societies. Once a minority interest, disease ecology has attracted more attention since the 1980s for its explanations of disease emergence, antibiotic resistance, bioterrorism, and the health impacts of climate change.

Biomedical Research↗

PubMed2004

The cotton rat: an underutilized animal model for human infectious diseases can now be exploited using specific reagents to cytokines, chemokines, and interferons.

The cotton rat represents the best or only animal model for a large number of human infectious diseases, and it may be unique among small laboratory animals in its susceptibility to several potential agents of bioterrorism. Although the cotton rat is a reliable model to define pathologic changes produced during infection with human pathogens, the lack of specific reagents has precluded a more extensive analysis of the molecular basis of pathogenesis. Here, we report the cloning of 24 cotton rat genes encoding various cytokines, chemokines, and interferons (IFNs). Analysis of the expression of most of these genes was performed by RT-PCR in cotton rat macrophages during treatment with lipopolysaccharide (LPS) and in cotton rat lungs after infection with influenza virus. The availability of these reagents will provide the tools for molecular analysis of pathogenesis and immune responses to a wide variety of pathogens and set the basis for the development of new prophylactic and therapeutic strategies against human infectious diseases.

Animals↗

PubMed2005

Preventing post-traumatic stress disorder after mass exposure to violence.

Bioterrorism preparedness plans must take into account the psychosocial consequences of exposure to mass violence. If possible, post-traumatic stress disorder (PTSD), which is associated with significant morbidity and cost, should be prevented. There are, however, no effective interventions that have been scaled up to prevent PTSD following mass exposure to violence. In fact, randomized controlled trials of the most commonly used preventive intervention, psychological debriefing, suggest no efficacy, or even potential harm. Fortunately, randomized controlled trials of cognitive behavioral therapy--that is, targeting individuals who are symptomatic in the weeks after trauma--reveal significant efficacy. Given the potential for repeated mass violence exposure, public health professionals need to refine methods for screening and tracking large numbers of casualties. At the same time, the use of telephone and internet-based cognitive behavioral therapy protocols should be further tested as strategies for bringing the only effective early intervention for PTSD to scale. Research on preventive pharmacotherapy for PTSD and on the effects of media exposure on PTSD severity is also a priority.

Humans↗

PubMed2005

Willingness of private physicians to be involved in smallpox preparedness and response activities.

BACKGROUND: The public health system continues its efforts to prepare for bioterrorist events, such as a smallpox outbreak, but may need to call on other health professionals to ensure sufficient capacity to implement preparedness plans. OBJECTIVE: The goal was to understand the willingness of primary care physicians to participate in possible smallpox pre- or post-event activities. METHODS: A 23-question mail survey was sent to a national random sample of 727 internists and 720 family physicians. After three mailings, a one-page version of the survey was sent to nonrespondents. RESULTS: Response rates were 26% for questions common to both surveys and 22% for questions on the longer survey only. Respondents to the survey expressed moderate support for participating in certain smallpox pre- and post-event activities. Under a pre-event scenario, many providers would be willing to vaccinate first responders in their practice, and roughly one-third would be willing to vaccinate patients in their practice or to work in a public health clinic as a vaccinator. Most physicians, however, would be unwilling to be vaccinated themselves. Under post-event conditions, most providers would be willing to vaccinate their own patients, and many would vaccinate other community members in their practice. CONCLUSIONS: Despite the low response rate, information from this study on the smallpox preparedness activities in which physicians are most willing to participate can help to inform efforts by public health officials and private physicians to collaborate on bioterrorism preparedness efforts.

Adult↗

PubMed2006

The dual-use dilemma for the life sciences: perspectives, conundrums, and global solutions.

The term "dual-use" traditionally has been used to describe technologies that could have both civilian and military usage, but this term has at least three different dimensions that pose a dilemma for modern biology and its possible misuse for hostile purposes: (1) ostensibly civilian facilities that are in fact intended for military or terrorist bioweapons development and production; (2) equipment and agents that could be misappropriated and misused for biological weapons development and production; and (3) the generation and dissemination of scientific knowledge that could be misapplied for biological weapons development and production. These three different aspects of the "dual-use dilemma" are frequently confused--each demands a distinct approach within a "web of prevention" in order to reduce the future risk of bioterrorism and biowarfare. This article discusses the nature of the different perspectives and divergent approaches as a contribution to finding a scientifically acceptable global solution to the problem posed by the dual-use dilemma. We propose that: (1) facilities that are intended for bioweapons development and production should be primarily prevented by a strengthened Biological and Toxin Weapons Convention (BTWC) effectively implemented in all nation states, one that includes provisions for adequate transparency to improve confidence and a mechanism for thorough inspections when there is sufficient cause, and enhanced law enforcement activities involving international cooperation and sharing of critical intelligence information; (2) potentially dual-use equipment and agents should be available to legitimate users for peaceful purposes, but strengthened national biosafety and physical and personnel biosecurity controls in all nations together with effective export controls should be implemented to limit the potential for the misappropriation of such equipment and materials; and (3) information should be openly accessible by the global scientific community, but a culture of responsible conduct involving the breadth of the international life sciences communities should be adopted to protect the ongoing revolution in the life sciences from being hijacked for hostile misuse of the knowledge generated and communicated by life scientists.

Access to Information↗

PubMed2006

Use of the internet to enhance infectious disease surveillance and outbreak investigation.

Modernization of electronic communication systems to facilitate infectious disease surveillance and outbreak investigation became a priority after the 2001 anthrax attacks. However, the extent to which communicable disease investigators are using web-based information resources, e-mail notifications, or secure information exchange systems to facilitate surveillance is unknown. To address this question, we conducted a survey in 2004 of state and local communicable disease investigators responsible for infectious disease surveillance and outbreak investigation in three states. The majority (70.7%) of the 297 respondents accessed the Internet for information regarding infectious disease surveillance and outbreaks at least weekly. Most (74%) respondents who searched for information from the Centers for Disease Control and Prevention (CDC) website reported that they found what they were looking for 75-100% of the time, compared with 54% who found the information from their state health department websites 75-100% of the time. One-third of respondents read e-mail notifications regarding outbreaks under investigation in their state less frequently than monthly; 34% of those enrolled in CDC's Epidemic Information Exchange (Epi-X) read e-mail notifications of new reports less frequently than monthly. Forty-seven (18%) respondents read ProMED-mail at least monthly, while 46% indicated they had never consulted MEDLINE/PubMed. Some progress has been made in use of the Internet to facilitate communication in infectious disease surveillance and outbreak investigation. Addressing barriers to access and usability of new information systems in conjunction with training and technical support could enhance infectious disease surveillance and timely investigation of outbreaks and bioterrorism events.

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

PubMed2006

Purdue University-Banfield National Companion Animal Surveillance Program for emerging and zoonotic diseases.

A National Companion Animal Surveillance Program (NCASP) was established at Purdue University to monitor clinical syndromes and diseases using the electronic medical records of >80,000 companion animals visiting >500 Banfield hospitals weekly in 44 states. With funding from the Centers for Disease Control and Prevention, NCASP was initially developed for syndromic surveillance of Category A agents of bioterrorism. Surveillance was expanded through inclusion of electronic reports from Antech Diagnostics, a nationwide network of integrated veterinary diagnostic laboratories serving >18,000 private veterinary practices. NCASP characterizes and displays temporal and spatial patterns of diseases in dogs, cats, and other companion animals. It detects unusual clusters of potential emerging/zoonotic infections and monitors flea and tick activity. Data is processed and analyzed using SAS and ESRI software products. The NCASP can be used by veterinarians to enhance their practice of evidence-based medicine by providing information needed to individualize vaccine protocols for animals in specific geographic areas.

Animals↗

PubMed2005

Vaccine design for severe acute respiratory syndrome coronavirus.

Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a new coronavirus (SARS-CoV). Recent studies suggest that SARS-CoV is zoonotic and may have a broad host range besides humans. Although the global outbreak of SARS has been contained, there are serious concerns over its re-emergence and bioterrorism potential. As a part of preparedness, development of a safe and effective vaccine is one of the highest priorities in fighting SARS. A number of candidate vaccines, using a variety of approaches, are under development. The first vaccine tested in clinical trial is made from the inactivated form of SARS-CoV. Several live attenuated, genetically engineered or vector vaccines encoding the SARS-CoV spike (S) protein have been in pre-clinical studies. These vaccine candidates are effective in terms of eliciting protective immunity in the vaccinated animals. However, caution should be taken with the safety of whole virus or full-length S protein-based immunogens in humans because they may induce harmful immune or inflammatory responses. We propose to use the receptor-binding domain (RBD) of SARS-CoV S protein (residues 318--510) for developing a safe and effective subunit SARS vaccine, as it is not only a functional domain that mediates virus-receptor binding but also a major neutralization determinant of SARSCoV. It has been demonstrated that the RBD of SARS-CoV S protein contains multiple conformational epitopes capable of inducing highly potent neutralizing antibody responses and protective immunity.

Animals↗

PubMed2004

MMR: risk, choice, chance.

The unfolding of the measles, mumps and rubella (MMR) controversy reveals some of the key features of the cultural climate affecting matters of health and illness in contemporary society. A high level of anxiety around issues of health is reflected in a heightened sense of individual vulnerability to environmental dangers (such as atmospheric pollution, electromagnetic fields, bioterrorism) and in a general aversion to risk, particularly in relation to children. This mood has proved responsive to views sceptical, if not hostile, towards science and medicine and associated professionals, particularly in the sphere of immunization. The result is that uptake of MMR vaccination in the UK has fallen, from a peak of 92% in the mid-1990s to a national level of 82% in 2003 (at the age of two); in London uptake is now less than 75%-much less in some areas-causing a significant risk of outbreaks of measles. In the USA too, the proportion of parents opting out of regulations requiring immunization as a condition of school entry has increased significantly in some areas, though these controversies appear to have had little impact so far in continental Europe.

Attitude to Health↗

PubMed2005

Working with transmissible spongiform encephalopathy agents.

The family of illnesses called transmissible spongiform encephalopathies (TSEs), or "prion" diseases, is composed of a small number of human and animal neurodegenerative diseases caused by unique pathogenic agents that are still not fully defined. They are best considered as "protein-misfolding diseases" (together with Alzheimer's disease, Parkinson's disease, and a few other rare examples) resulting from the conversion of a normal body protein into a misfolded amyloid multimer. The pathogenic agents display a unique resistance to conventional disinfection methods and an extraordinary environmental durability, which has led the US Department of Agriculture to designate the causative agent of bovine spongiform encephalopathy as a bioterrorism security threat. In this review, precautions and regulations concerning the handling of TSE agents are discussed in relation to personnel and environmental biosafety.

Animals↗

PubMed2005

Serendipitous insights involving nonhuman primates.

Serendipity is discussed as a form of controlled chaos, a phenomenon in a class with synchronicity and other actions affecting research in terms of theory versus observation (e.g., "optional stopping"). Serendipity is a fundamental aspect of basic research, a profitable and normal outcome in the context of "informed observation." The serendipitous finding fits into the following pattern: it is unanticipated, anomalous, and strategic. All observations that have meaning must fit into some context in the observer's mind or suggest a revolutionary new context. It is critically important to maintain access to the resources provided by established primate centers and similar laboratories to capitalize in a timely way on serendipitous findings and to benefit from valuable discoveries made in more directly targeted development investments. Examples are given of serendipitous insights gained in experimentation and observation relative to nonhuman primate research, including both broad and narrow topics. Genomics, which uses comparison-based strategies and capitalizes on the DNA sequences of genetic information, presents what might seem the basis for endless serendipity because nonhuman primates are likely to share most genes present in the human genome. Other topics discussed include infant behavior, birth periodicity, leprosy, cystic fibrosis, environmental enrichment, endocrinology, drug development, and the rapidly expanding study of infectious diseases and pathogen-based bioterrorism.

Animals↗

PubMed2003

Metabolic effects of infection on protein and energy status.

A review of some of the seminal studies of metabolism during various infections indicates that similar patterns of metabolic alterations occur during these illnesses. This patterned metabolic array occurs whether the infection is caused by a gram-positive or a gram-negative bacterium, a rickettsia or a virus, or is respiratory or systemic. In all instances, the previously healthy host responds to infection with cytokine-mediated alterations that appear to occur in proportion to the infectious challenge and to the likelihood of death. These alterations also can occur in the vaccinated host, if the infectious challenge is sufficiently great. Because of their widespread occurrence and seemingly ingrained status, these metabolic alterations may be presumed to be of survival benefit to the host. Whether this patterned array of metabolic sequelae is of benefit to the host, or even to the species, its widespread and systematic occurrence allows it to be of value in assessing the safety and efficacy of vaccines and drugs to prevent or treat a wide variety of infections. In this era of bioterrorism, wherein drugs and vaccines may have to be approved for human use without clinical trials and solely on the basis of animal data, these cytokine-mediated metabolic sequelae can aid in the rational selection of drug and vaccine candidates.

Amino Acids↗

PubMed2006

Supplementation with active hexose correlated compound increases the innate immune response of young mice to primary influenza infection.

The emergence of H5N1 avian influenza and the threat of new or adapted viruses in bioterrorism have created an urgent interest in identifying agents to enhance the immune response to primary virus infection. Active hexose correlated compound (AHCC) is a natural mushroom extract reported to increase natural killer (NK) cell activity, survival, and bacterial clearance in young mice. However, the effects of AHCC on the response to viral infections have not been studied. In this study, young C57BL/6 mice were supplemented with 1 g AHCC/(kg body weight x d) for 1 wk prior to and throughout infection with influenza A (H1N1, PR8). Supplementation increased survival, decreased the severity of infection, and shortened recovery time following intranasal infection with flu, as determined by the recovery of body weight and epithelial integrity in the lungs. AHCC increased NK activity in lungs at d 1 (P < 0.05) and d 4 (P < 0.01) and in the spleen at d 2 postinfection (P < 0.01). Supplementation increased the percentage (P < 0.05) and number (P < 0.01) of NK1.1+ cells in the lung and reduced the infiltration of lymphocytes and macrophages compared with controls (P < 0.01). These data suggest that AHCC supplementation boosts NK activity, improves survival, and reduces the severity of influenza infection in young mice. Bolstering innate immunity with dietary bioactives may be one avenue for improving the immune response to primary flu infection.

Adjuvants, Immunologic↗

PubMed2004

The history of woolsorters' disease: a Yorkshire beginning with an international future?

Woolsorters' disease was a feared industrial disease associated primarily with Yorkshire's textile industry of the nineteenth and early twentieth centuries. Early occupational health methods were attempted locally before concerted national efforts produced legislative measures. When its link with anthrax was established, attention in prevention focused upon chemical disinfection methods. Together, these factors were instrumental in decreasing the incidence of woolsorters' disease. However, by the beginning of the Second World War, the lack of treatment options for anthrax meant that the bacterium was experimented upon as a potential war-winning weapon. Today, woolsorters' disease and other industrial manifestations of anthrax are extremely rare, but the increasing threat of bioterrorism means that the international dread and historical lessons of this significant condition should never be forgotten. Consequently, this paper reveals the history of woolsorters' disease in order to remind those involved in occupational medicine today of the dread it caused both physicians and workers in previous generations.

Animals↗