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PubMed2003

Spatial pattern separation of chemicals and frequency-independent components by terahertz spectroscopic imaging.

We separated the component spatial patterns of frequency-dependent absorption in chemicals and frequency-independent components such as plastic, paper, and measurement noise in terahertz (THz) spectroscopic images, using known spectral curves. Our measurement system, which uses a widely tunable coherent THz-wave parametric oscillator source, can image at a specific frequency in the range 1-2 THz. The component patterns of chemicals can easily be extracted by use of the frequency-independent components. This method could be successfully used for nondestructive inspection for the detection of illegal drugs and devices of bioterrorism concealed, e.g., inside mail and packages.

Journal Article↗

PubMedDate not supplied

The unfulfilled promise of public health: déjà vu all over again.

Many complain about public health's weak infrastructure and poor capacity to respond to threats of bioterrorism. Such complaints are but the anxiety-heightened expression of a periodic rediscovery of the deficiencies and unfulfilled promise of U.S. public health. An overview of more than two centuries suggests that where we are now with public health has been shaped by our earlier, limited, and crisis-focused responses to changing disease threats. We have failed to sustain progress in any coherent manner. If we do not wish to repeat past mistakes, we should learn lessons from the past to guide us in the future.

Communicable Disease Control↗

PubMedDate not supplied

The medicine cabinet: what's in it, why, and can we change the contents?

The failure of the pharmaceutical industry to produce drugs for common chronic diseases, emerging diseases, and the potential threats of bioterrorism or the spread of tropical diseases contrasts sharply with the industry's output of lifestyle and "me-too" drugs. In this paper we review the decision-making process that resulted in our current portfolio of medicines and offer several alternatives to better align business incentives with medical need.

Decision Making, Organizational↗

PubMedDate not supplied

Encouraging the development of new vaccines.

Investment in the development of new vaccines is suboptimal. Changing this situation requires a creative blend of "push" and "pull" strategies. One successful policy model is the Orphan Drug Act, whose key features include large research and development (R and D) tax credits as well as Food and Drug Administration (FDA) counseling and priority review. Such supply-side R and D incentive provisions can be combined with demand-side mandates and vouchers to encourage development of new vaccines. Guaranteed-purchase funds and other pull mechanisms are useful supplementary incentives in the cases of vaccines for bioterrorism and neglected diseases of poverty.

Motivation↗

PubMedDate not supplied

The making and adoption of health data standards.

Health data standards are key to the U.S. quest to create an aggregated, patient-centric electronic health record; to build regional health information networks; to interchange data among independent sites involved in a person's care; to create a population database for health surveillance and for bioterrorism defense; and to create a personal health record. This paper discusses why health data standards are required, the process of creating those standards, the groups creating those standards, and some of the problems and issues that are affecting the progress and acceptance of standards. It makes a recommendation for dealing with those issues.

Diffusion of Innovation↗

PubMedDate not supplied

The impact of globalization on vaccine development and availability.

Globalization is likely to affect many aspects of public health, one of which is vaccine-preventable communicable diseases. Important forces include increased funding initiatives supporting immunization at the global level; regulatory harmonization; widespread intellectual property rights provisions through the World Trade Organization agreements; the emergence of developing-country manufacturers as major players in vaccine supply; and the appearance of new communicable disease threats, including those potentially linked to bioterrorism. All of these forces can affect, either positively and negatively, the development and availability of vaccines. Harnessing these will be a challenge for policymakers and immunization stakeholders.

Commerce↗

PubMed2004

Should dentists become 'oral physicians'? Yes, dentists should become 'oral physicians'.

In summary, a new designation for the dental profession is warranted, not because paramedical professionals have done it, but because the new designation is appropriate for what they are able to do. Moreover, it can be done now with little resistance or fanfare. As has been suggested by others, changing the name "dentist" to the name "oral physician" would result in several benefits: dentists' being recognized as providers of services such as tobacco-use cessation, oral cancer screenings, nutritional counseling and, most recently, as a major health care resource for dealing with bioterrorism; the public's visiting dental professionals for services other than traditional dental procedures; the profession's being more likely to teach and provide services outside of traditional dental procedures; third-party payers' being more likely to pay for services other than traditional dental procedures; the improvement in the public's oral health that would result from patients' visiting "oral physicians" for services other than traditional dental procedures.

Delivery of Health Care↗

PubMed2003

Under scrutiny: smallpox vaccine recommendations.

The eradication of smallpox is widely considered to be one of the great achievements of public health. However, international terrorism in the US and elsewhere has led to increasing concern about vulnerability to a smallpox bioterror attack. Timely vaccination is highly protective against smallpox but carries risks of morbidity and mortality. Significant debate has therefore emerged regarding the optimal strategy for defence. In principle, there are three options: either mass or limited vaccination prior to an attack; quarantine and vaccination of all suspected cases of smallpox following an attack with isolation and vaccination of potential case contacts; and mass vaccination after the identification of a case of smallpox. This paper reviews smallpox disease, smallpox vaccination and the development of current smallpox vaccination policy in the US. Mathematical models of the spread of smallpox and control strategies are reviewed to explore specific smallpox vaccine policy considerations. Limitations of these models are considered and recommendations are made for future research.

Humans↗

PubMed2004

Use of cytokines in infection.

Infectious disease remains an ever-growing health concern worldwide due to increasing antibiotic-resistant microbial strains, immune-compromised populations, international traffic and globalisation, and bioterrorism. There exists an urgent need to develop novel prophylactic and therapeutic strategies. In addition to classic antibiotic therapeutics, immune-modulatory molecules such as cytokines or their inhibitors represent a promising form of antimicrobial therapeutics or immune adjuvant used for the purpose of vaccination. These molecules, in the form of either recombinant protein or transgene, exert their antimicrobial effect by enhancing infectious agent-specific immune activation or memory development, or by dampening undesired inflammatory and immune responses resulting from infection and host defence mechanisms. In the last two decades, a number of cytokine therapy-based experimental and clinical trials have been conducted, and some of these efforts have led to the routine clinical use of cytokines. For instance, although IFNs have been used to treat hepatitis C with great success, many other cytokines are yet to be fully evaluated for their antimicrobial potential. This review discusses the biology and therapeutic potential of selected immune modulatory cytokines and their inhibitors, including granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, IFN-gamma, IL-12 and TNF.

Colony-Stimulating Factors↗

PubMed2006

Decision analysis in planning for a polio outbreak in the United States.

OBJECTIVE: Global eradication of poliomyelitis may soon be achieved, but circulating polioviruses could reemerge years after eradication by reversion of live attenuated oral vaccine virus to a virulent form, laboratory stock mishandling, or bioterrorism. If a poliomyelitis outbreak occurs in the United States, access to a vaccine stockpile to interrupt viral spread will be necessary. Options for the stockpile include the inactivated polio vaccine and the live-attenuated trivalent and monovalent oral poliovirus vaccines. With differences in immunogenicity, adverse effects, availability, and other issues, the optimal vaccine choice for the stockpile is not clear. We sought to compare vaccine interventions for poliomyelitis outbreak control. DESIGN: We applied decision analysis to 8 strategies for outbreak control: no intervention, 1 or 2 inactivated polio vaccine doses, 1 or 2 trivalent oral poliovirus vaccine doses, 1 or 2 monovalent oral poliovirus vaccine doses, and sequential inactivated polio vaccine-monovalent oral poliovirus vaccine. Historical data from outbreaks in developed countries were used to estimate the risk of paralytic disease after a hypothetical reintroduction of circulating polioviruses. The outcome measure was cases of paralytic poliomyelitis. RESULTS: Monovalent oral poliovirus vaccine provided optimal outbreak control in most scenarios because of high seroconversion rates with 1 dose. Control provided by trivalent oral poliovirus vaccine and inactivated polio vaccine was equivalent at high vaccine coverage rates. At low intervention rates, trivalent oral poliovirus vaccine produced fewer paralytic cases than inactivated polio vaccine in highly immune populations but more cases than inactivated polio vaccine in poorly immunized groups because of secondary transmission of oral poliovirus vaccine virus and vaccine-derived viruses. CONCLUSIONS: This model suggests that monovalent oral poliovirus vaccine would be the most advantageous vaccine for outbreak control. If a monovalent oral poliovirus vaccine stockpile is impractical, the optimal vaccine choice depends on the previous immunity and the anticipated intervention rates.

Antibodies, Viral↗

PubMed2002

Melioidosis vaccines.

Melioidosis is a disease caused by the facultative intracellular pathogen Burkholderia pseudomallei iand is associated with a high mortality rate. Melioidosis is endemic in the tropics of southeast Asia and northern Australia and is of worldwide concern, particularly as it is a potential agent of bioterrorism or biological warfare. Also of concern is the lack of a fully effective antibiotic regime, as cases of bacteremia have unacceptably high mortality rates and relapse of melioidosis is common. This review focuses on the approaches that have been undertaken towards the development of an effective vaccine against this disease and highlights current strategies being used to move towards finalizing such a vaccine.

Antigens, Bacterial↗

PubMed2003

Towards a vaccine against Ebola virus.

Ebola virus infection causes hemorrhagic fever with high mortality rates in humans and nonhuman primates. Currently, there are no vaccines or therapies approved for human use. Outbreaks of Ebola virus have been infrequent, largely confined to remote locations in Africa and quarantine of sick patients has been effective in controlling epidemics. In the past, this small global market has generated little commercial interest for developing an Ebola virus vaccine. However, heightened awareness of bioterrorism advanced by the events surrounding September 11, 2001, concomitant with knowledge that the former Soviet Union was evaluating Ebola virus as a weapon, has dramatically changed perspectives regarding the need for a vaccine against Ebola virus. This review takes a brief historic look at attempts to develop an efficacious vaccine, provides an overview of current vaccine candidates and highlights strategies that have the greatest potential for commercial development.

Animals↗

PubMed2004

Lassa fever vaccine.

Lassa fever remains a serious challenge to public health in West Africa threatening both local residents in rural areas and those who serve them, particularly medical care providers. Given the ecology of the rodent host and conditions in the endemic area, a vaccine is mandatory for control. The challenge is to overcome the scientific, political and economic obstacles to producing a human use vaccine candidate. There are some scientific issues to resolve. It is known that the G-protein confers protection but we do not know its duration. If the N-protein is also included there may be a better duration of protection but it is unclear whether the N-protein as a vaccine may possibly enhance the infection. The original vaccinia vector must be replaced by new vectors, chimeras or by delivering DNA in some format. A live vaccine is attractive because it can confer protection in a single shot. A killed vaccine is more stable, particularly for distribution in the tropics but usually requires repeated shots. For practical reasons a live vaccine format should probably be pursued, which could then be combined with a yellow fever vaccine, using the same cold chains, since this disease occupies the same endemic areas in West Africa. Lassa vaccine initiatives have suffered from a lack of funding in the past but bioterrorism has brought new resources to Lassa virus science. Adequate funding and applications of new vaccine technologies give hope that we may soon see a vaccine in clinical trials. However, the difficulty of conducting trials in endemic areas and lack of political stability remain serious problems.

Africa, Western↗

PubMed2004

Progress toward development of an inhalation vaccine against botulinum toxin.

The looming threat of bioterrorism has enhanced interest in the development of vaccines against agents such as botulinum toxin. This in turn has stimulated efforts to create vaccines that are effective by the oral and inhalation routes. Recently, considerable progress has been made in creating an inhalation vaccine against botulism. This work stems from the discovery that a polypeptide that represents a third of the toxin molecule retains the ability to be adsorbed from the airway and to evoke an immune response but retains none of the adverse effects of the native toxin. Interestingly, this polypeptide can also serve as a carrier molecule in the creation of inhalation vaccines against other pathogens.

Administration, Inhalation↗

PubMed2005

Ricin: current understanding and prospects for an antiricin vaccine.

Ricin is a potent cytotoxin that can be rapidly internalized into mammalian cells leading to cell death. The ease in obtaining the toxin and its deadly nature combine to implicate ricin as a convenient agent for bioterrorism. Research into the mechanism of toxicity, as well as strategies for treatment and protection from the toxin has been widely undertaken for a number of years. This article reviews the current understanding of the mechanism of action of the toxin, the clinical effects of ricin intoxication and how these relate to current and continuing prospects for vaccine development.

Amino Acid Sequence↗

PubMed2004

Emerging infectious diseases: vulnerabilities, contributing factors and approaches.

We live in an ever more connected global village linked through international travel, politics, economics, culture and human-human and human-animal interactions. The realization that the concept of globalization includes global exposure to disease-causing agents that were formerly confined to small, remote areas and that infectious disease outbreaks can have political, economic and social roots and effects is becoming more apparent. Novel infectious disease microbes continue to be discovered because they are new or newly recognized, have expanded their geographic range, have been shown to cause a new disease spectrum, have jumped the species barrier from animals to humans, have become resistant to antimicrobial agents, have increased in incidence or have become more virulent. These emerging infectious disease microbes may have the potential for use as agents of bioterrorism. Factors involved in the emergence of infectious diseases are complex and interrelated and involve all classifications of organisms transmitted in a variety of ways. In 2003, outbreaks of interest included severe acute respiratory syndrome, monkeypox and avian influenza. Information from the human genome project applied to microbial organisms and their hosts will provide new opportunities for detection, diagnosis, treatment, prevention, control and prognosis. New technology related not only to genetics but also to satellite and monitoring systems will play a role in weather, climate and the approach to environmental manipulations that influence factors contributing to infectious disease emergence and control. Approaches to combating emerging infectious diseases include many disciplines, such as animal studies, epidemiology, immunology, ecology, environmental studies, microbiology, pharmacology, other sciences, health, medicine, public health, nursing, cultural, political and social studies, all of which must work together. Appropriate financial support of the public health infrastructure including surveillance, prevention, communication, adherence techniques and the like will be needed to support efforts to address emerging infectious disease threats.

Climate↗

PubMed2006

Bioinformatics and data mining in proteomics.

Proteomic studies involve the identification as well as qualitative and quantitative comparison of proteins expressed under different conditions, and elucidation of their properties and functions, usually in a large-scale, high-throughput format. The high dimensionality of data generated from these studies will require the development of improved bioinformatics tools and data-mining approaches for efficient and accurate data analysis of biological specimens from healthy and diseased individuals. Mining large proteomics data sets provides a better understanding of the complexities between the normal and abnormal cell proteome of various biological systems, including environmental hazards, infectious agents (bioterrorism) and cancers. This review will shed light on recent developments in bioinformatics and data-mining approaches, and their limitations when applied to proteomics data sets, in order to strengthen the interdependence between proteomic technologies and bioinformatics tools.

Computational Biology↗

PubMedDate not supplied

Globalization and disease: in an unequal world, unequal health!

In this paper, originally presented at an event held by the National Institutes of Health (NIH) in the United States, the author analyzes the repercussions of globalization on various health aspects: the spread of infectious and parasitic diseases, bioterrorism, and new behavioral patterns in health, among others. He goes on to examine the positive and negative effects of international agreements on health, particularly in the trade area, including the TRIPS Agreement on medicines in the area of public health. The paper concludes that the resumption of cooperation among nations is the best way to achieve world progress in public health.

Acquired Immunodeficiency Syndrome↗