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The impact of 9/11 on HIV policy and politics.

In the aftermath of 9/11, shifts in federal priorities have threatened HIV funding, public financing of the health and public health infrastructures in which HIV services are embedded, and key HIV policies. However, the best strategies to address terrorism, especially bioterrorism, also strengthen its capacity for HIV surveillance, prevention, and care. AIDS advocates need to argue for appropriate antiterrorism measures that focus resources and technology on upgrading the capacity and scope of our health care and public health systems. This broad focus is not only the best protection against terrorism, it benefits all Americans, including people living with HIV.

Financing, Government↗

PubMed2006

Genotyping of Bacillus anthracis strains based on automated capillary 25-loci multiple locus variable-number tandem repeats analysis.

BACKGROUND: The genome of Bacillus anthracis, the etiological agent of anthrax, is highly monomorphic which makes differentiation between strains difficult. A Multiple Locus Variable-number tandem repeats (VNTR) Analysis (MLVA) assay based on 20 markers was previously described. It has considerable discrimination power, reproducibility, and low cost, especially since the markers proposed can be typed by agarose-gel electrophoresis. However in an emergency situation, faster genotyping and access to representative databases is necessary. RESULTS: Genotyping of B. anthracis reference strains and isolates from France and Italy was done using a 25 loci MLVA assay combining 21 previously described loci and 4 new ones. DNA was amplified in 4 multiplex PCR reactions and the length of the resulting 25 amplicons was estimated by automated capillary electrophoresis. The results were reproducible and the data were consistent with other gel based methods once differences in mobility patterns were taken into account. Some alleles previously unresolved by agarose gel electrophoresis could be resolved by capillary electrophoresis, thus further increasing the assay resolution. One particular locus, Bams30, is the result of a recombination between a 27 bp tandem repeat and a 9 bp tandem repeat. The analysis of the array illustrates the evolution process of tandem repeats. CONCLUSION: In a crisis situation of suspected bioterrorism, standardization, speed and accuracy, together with the availability of reference typing data are important issues, as illustrated by the 2001 anthrax letters event. In this report we describe an upgrade of the previously published MLVA method for genotyping of B. anthracis and apply the method to the typing of French and Italian B. anthracis strain collections. The increased number of markers studied compared to reports using only 8 loci greatly improves the discrimination power of the technique. An Italian strain belonging to the B branch was described, and two new branches, D and E, are proposed. Owing to the upgrading achieved here, precise genotyping can now be produced either by automated capillary electrophoresis, or by the more accessible but slower and for some markers slightly less accurate agarose gel methodology.

Automation↗

PubMed2005

An automated, broad-based, near real-time public health surveillance system using presentations to hospital Emergency Departments in New South Wales, Australia.

BACKGROUND: In a climate of concern over bioterrorism threats and emergent diseases, public health authorities are trialling more timely surveillance systems. The 2003 Rugby World Cup (RWC) provided an opportunity to test the viability of a near real-time syndromic surveillance system in metropolitan Sydney, Australia. We describe the development and early results of this largely automated system that used data routinely collected in Emergency Departments (EDs). METHODS: Twelve of 49 EDs in the Sydney metropolitan area automatically transmitted surveillance data from their existing information systems to a central database in near real-time. Information captured for each ED visit included patient demographic details, presenting problem and nursing assessment entered as free-text at triage time, physician-assigned provisional diagnosis codes, and status at departure from the ED. Both diagnoses from the EDs and triage text were used to assign syndrome categories. The text information was automatically classified into one or more of 26 syndrome categories using automated "naïve Bayes" text categorisation techniques. Automated processes were used to analyse both diagnosis and free text-based syndrome data and to produce web-based statistical summaries for daily review. An adjusted cumulative sum (cusum) was used to assess the statistical significance of trends. RESULTS: During the RWC the system did not identify any major public health threats associated with the tournament, mass gatherings or the influx of visitors. This was consistent with evidence from other sources, although two known outbreaks were already in progress before the tournament. Limited baseline in early monitoring prevented the system from automatically identifying these ongoing outbreaks. Data capture was invisible to clinical staff in EDs and did not add to their workload. CONCLUSION: We have demonstrated the feasibility and potential utility of syndromic surveillance using routinely collected data from ED information systems. Key features of our system are its nil impact on clinical staff, and its use of statistical methods to assign syndrome categories based on clinical free text information. The system is ongoing, and has expanded to cover 30 EDs. Results of formal evaluations of both the technical efficiency and the public health impacts of the system will be described subsequently.

Anniversaries and Special Events↗

PubMed2006

Approaches to the evaluation of outbreak detection methods.

BACKGROUND: An increasing number of methods are being developed for the early detection of infectious disease outbreaks which could be naturally occurring or as a result of bioterrorism; however, no standardised framework for examining the usefulness of various outbreak detection methods exists. To promote comparability between studies, it is essential that standardised methods are developed for the evaluation of outbreak detection methods. METHODS: This analysis aims to review approaches used to evaluate outbreak detection methods and provide a conceptual framework upon which recommendations for standardised evaluation methods can be based. We reviewed the recently published literature for reports which evaluated methods for the detection of infectious disease outbreaks in public health surveillance data. Evaluation methods identified in the recent literature were categorised according to the presence of common features to provide a conceptual basis within which to understand current approaches to evaluation. RESULTS: There was considerable variation in the approaches used for the evaluation of methods for the detection of outbreaks in public health surveillance data, and appeared to be no single approach of choice. Four main approaches were used to evaluate performance, and these were labelled the Descriptive, Derived, Epidemiological and Simulation approaches. Based on the approaches identified, we propose a basic framework for evaluation and recommend the use of multiple approaches to evaluation to enable a comprehensive and contextualised description of outbreak detection performance. CONCLUSION: The varied nature of performance evaluation demonstrated in this review supports the need for further development of evaluation methods to improve comparability between studies. Our findings indicate that no single approach can fulfil all evaluation requirements. We propose that the cornerstone approaches to evaluation identified provide key contributions to support internal and external validity and comparability of study findings, and suggest these be incorporated into future recommendations for performance assessment.

Benchmarking↗

PubMed2004

Estimation of hospital emergency room data using OTC pharmaceutical sales and least mean square filters.

BACKGROUND: Surveillance of Over-the-Counter pharmaceutical (OTC) sales as a potential early indicator of developing public health conditions, in particular in cases of interest to Bioterrorism, has been suggested in the literature. The data streams of interest are quite non-stationary and we address this problem from the viewpoint of linear adaptive filter theory: the clinical data is the primary channel which is to be estimated from the OTC data that form the reference channels. METHOD: The OTC data are grouped into a few categories and we estimate the clinical data using each individual category, as well as using a multichannel filter that encompasses all the OTC categories. The estimation (in the least mean square sense) is performed using an FIR (Finite Impulse Response) filter and the normalized LMS algorithm. RESULTS: We show all estimation results and present a table of effectiveness of each OTC category, as well as the effectiveness of the combined filtering operation. Individual group results clearly show the effectiveness of each particular group in estimating the clinical hospital data and serve as a guide as to which groups have sustained correlations with the clinical data. CONCLUSION: Our results indicate that Multichannel adaptive FIR least squares filtering is a viable means of estimating public health conditions from OTC sales, and provide quantitative measures of time dependent correlations between the clinical data and the OTC data channels.

Adolescent↗

PubMed2006

In vitro susceptibilities of Brucella melitensis isolates to eleven antibiotics.

BACKGROUND: Brucellosis is an endemic disease present in many countries worldwide, but it is rare in Europe and North America. Nevertheless brucella is included in the bacteria potentially used for bioterrorism. The aim of this study was the investigation of the antibiotic susceptibility profile of brucella isolates from areas of the eastern Mediterranean where it has been endemic. METHODS: The susceptibilities of 74 Brucella melitensis isolates derived from clinical samples (57) and animal products (17) were tested in vitro. The strains originate from Crete (59), Cyprus (10), and Syria (5). MICs of tetracycline, rifampicin, streptomycin, gentamicin, norfloxacin, ciprofloxacin, levofloxacin, trimethoprim/sulfamethoxazole, ampicillin, amoxicillin/clavulanic acid, and erythromycin were detected by E-test method. The NCCLS criteria for slow growing bacteria were considered to interpret the results. RESULTS: All the isolates were susceptible to tetracycline, streptomycin, gentamicin, ciprofloxacin, norfloxacin, and levofloxacin. Two isolates presented reduced susceptibility to rifampicin (MIC value: 1.5 mg/l) and eight to SXT (MIC values: 0.75-1.5 mg/l). Erythromycin had the highest (4 mg/l) MIC90value and both norfloxacin and erythromycin the highest (1.5 mg/l) MIC50 value. CONCLUSION: Brucella isolates remain susceptible in vitro to most antibiotics used for treatment of brucellosis. The establishment of a standardized antibiotic susceptibility method for Brucella spp would be useful for resistance determination in these bacteria and possible evaluation of bioterorism risks.

Animals↗

PubMed2004

Towards evidence-based, GIS-driven national spatial health information infrastructure and surveillance services in the United Kingdom.

The term "Geographic Information Systems" (GIS) has been added to MeSH in 2003, a step reflecting the importance and growing use of GIS in health and healthcare research and practices. GIS have much more to offer than the obvious digital cartography (map) functions. From a community health perspective, GIS could potentially act as powerful evidence-based practice tools for early problem detection and solving. When properly used, GIS can: inform and educate (professionals and the public); empower decision-making at all levels; help in planning and tweaking clinically and cost-effective actions, in predicting outcomes before making any financial commitments and ascribing priorities in a climate of finite resources; change practices; and continually monitor and analyse changes, as well as sentinel events. Yet despite all these potentials for GIS, they remain under-utilised in the UK National Health Service (NHS). This paper has the following objectives: (1) to illustrate with practical, real-world scenarios and examples from the literature the different GIS methods and uses to improve community health and healthcare practices, e.g., for improving hospital bed availability, in community health and bioterrorism surveillance services, and in the latest SARS outbreak; (2) to discuss challenges and problems currently hindering the wide-scale adoption of GIS across the NHS; and (3) to identify the most important requirements and ingredients for addressing these challenges, and realising GIS potential within the NHS, guided by related initiatives worldwide. The ultimate goal is to illuminate the road towards implementing a comprehensive national, multi-agency spatio-temporal health information infrastructure functioning proactively in real time. The concepts and principles presented in this paper can be also applied in other countries, and on regional (e.g., European Union) and global levels.

Journal Article↗

PubMed2005

GIDEON: a comprehensive Web-based resource for geographic medicine.

GIDEON (Global Infectious Diseases and Epidemiology Network) is a web-based computer program designed for decision support and informatics in the field of Geographic Medicine. The first of four interactive modules generates a ranked differential diagnosis based on patient signs, symptoms, exposure history and country of disease acquisition. Additional options include syndromic disease surveillance capability and simulation of bioterrorism scenarios. The second module accesses detailed and current information regarding the status of 338 individual diseases in each of 220 countries. Over 50,000 disease images, maps and user-designed graphs may be downloaded for use in teaching and preparation of written materials. The third module is a comprehensive source on the use of 328 anti-infective drugs and vaccines, including a listing of over 9,500 international trade names. The fourth module can be used to characterize or identify any bacterium or yeast, based on laboratory phenotype. GIDEON is an up-to-date and comprehensive resource for Geographic Medicine.

Journal Article↗

PubMed2003

A Canadian national survey of attitudes and knowledge regarding preventive vaccines.

BACKGROUND: Vaccines have virtually eliminated many diseases, but public concerns about their safety could undermine future public health initiatives. OBJECTIVE: To determine Canadians' attitudes and knowledge about vaccines, particularly in view of increasing public concern about bioterrorism and the possible need for emergency immunizations after weaponized anthrax incidents and the events of September 11, 2001. METHOD: A 20-question survey based on well-researched dimensions of vaccine responsiveness was telephone-administered to a random sample of N = 1330 adult Canadians in January, 2002. RESULTS: 1057 (79.5%) completed the survey. Respondents perceived vaccines to be highly effective and demonstrated considerable support for further vaccine research. However, results also indicate a lack of knowledge about vaccines and uncertainty regarding the safety. CONCLUSIONS: Support for vaccines is broad but shallow. While Canadians hold generally positive attitudes about vaccines, support could be undermined by widely publicized adverse events. Better public education is required to maintain support for future public health initiatives.

Journal Article↗

PubMed2004

Human anti-anthrax protective antigen neutralizing monoclonal antibodies derived from donors vaccinated with anthrax vaccine adsorbed.

BACKGROUND: Potent anthrax toxin neutralizing human monoclonal antibodies were generated from peripheral blood lymphocytes obtained from Anthrax Vaccine Adsorbed (AVA) immune donors. The anti-anthrax toxin human monoclonal antibodies were evaluated for neutralization of anthrax lethal toxin in vivo in the Fisher 344 rat bolus toxin challenge model. METHODS: Human peripheral blood lymphocytes from AVA immunized donors were engrafted into severe combined immunodeficient (SCID) mice. Vaccination with anthrax protective antigen and lethal factor produced a significant increase in antigen specific human IgG in the mouse serum. The antibody producing lymphocytes were immortalized by hybridoma formation. The genes encoding the protective antibodies were rescued and stable cell lines expressing full-length human immunoglobulin were established. The antibodies were characterized by; (1) surface plasmon resonance; (2) inhibition of toxin in an in vitro mouse macrophage cell line protection assay and (3) in vivo in a Fischer 344 bolus lethal toxin challenge model. RESULTS: The range of antibodies generated were diverse with evidence of extensive hyper mutation, and all were of very high affinity for PA83~1 x 10-10-11M. Moreover all the antibodies were potent inhibitors of anthrax lethal toxin in vitro. A single IV dose of AVP-21D9 or AVP-22G12 was found to confer full protection with as little as 0.5x (AVP-21D9) and 1x (AVP-22G12) molar equivalence relative to the anthrax toxin in the rat challenge prophylaxis model. CONCLUSION: Here we describe a powerful technology to capture the recall antibody response to AVA vaccination and provide detailed molecular characterization of the protective human monoclonal antibodies. AVP-21D9, AVP-22G12 and AVP-1C6 protect rats from anthrax lethal toxin at low dose. Aglycosylated versions of the most potent antibodies are also protective in vivo, suggesting that lethal toxin neutralization is not Fc effector mediated. The protective effect of AVP-21D9 persists for at least one week in rats. These potent fully human anti-PA toxin-neutralizing antibodies are attractive candidates for prophylaxis and/or treatment against Anthrax Class A bioterrorism toxins.

Journal Article↗

PubMed2004

Managing emerging infectious diseases: Is a federal system an impediment to effective laws?

In the 1980's and 1990's HIV/AIDS was the emerging infectious disease. In 2003-2004 we saw the emergence of SARS, Avian influenza and Anthrax in a man made form used for bioterrorism. Emergency powers legislation in Australia is a patchwork of Commonwealth quarantine laws and State and Territory based emergency powers in public health legislation. It is time for a review of such legislation and time for consideration of the efficacy of such legislation from a country wide perspective in an age when we have to consider the possibility of mass outbreaks of communicable diseases which ignore jurisdictional boundaries.

Editorial↗

PubMed2001

The World Trade Center attack. Eye witness: observations of a physician on the outside looking in.

Having personally witnessed the destruction at the World Trade Center on 11 September 2001, this paper presents my personal feelings and observations as an observer of both disaster and terror. Aside from the unimaginable horror as a result of the carnage, a feeling of helplessness was particularly prominent due to the inability to be able to care for casualties since most victims were fatalities. The passage of time has enabled a return to normalcy, however 'normalcy' carries a new definition due to the vastness of the tragedy and the sudden threat of bioterrorism and other weapons of mass destruction.

Anecdotes as Topic↗

PubMed2005

Clinical review: SARS - lessons in disaster management.

Disaster management plans have traditionally been required to manage major traumatic events that create a large number of victims. Infectious diseases, whether they be natural (e.g. SARS [severe acute respiratory syndrome] and influenza) or the result of bioterrorism, have the potential to create a large influx of critically ill into our already strained hospital systems. With proper planning, hospitals, health care workers and our health care systems can be better prepared to deal with such an eventuality. This review explores the Toronto critical care experience of coping in the SARS outbreak disaster. Our health care system and, in particular, our critical care system were unprepared for this event, and as a result the impact that SARS had was worse than it could have been. Nonetheless, we were able to organize a response rapidly during the outbreak. By describing our successes and failures, we hope to help others to learn and avoid the problems we encountered as they develop their own disaster management plans in anticipation of similar future situations.

Communicable Disease Control↗

PubMed2006

Innate immune response to Francisella tularensis is mediated by TLR2 and caspase-1 activation.

Francisella tularensis, a gram-negative, facultative, intracellular bacterium, is the etiologic agent of tularemia and a category A bioterrorism agent. Little is known about the mechanism of pathogenesis of tularemia. In this paper, we describe the interaction of the live vaccine strain of F. tularensis with the innate immune system. We have found that in human and mouse dendritic cells, F. tularensis elicited a powerful inflammatory response, characterized by production of a number of cytokines and chemokines. Using cells derived from TLR2-deficient mice and in vitro transfection assays, we demonstrated that this response was mediated by TLR2 and did not require the LPS-binding protein. F. tularensis appeared to activate TLR2/TLR1 and TLR2/TLR6 heterodimers. IL-1beta secretion, a reflection of caspase-1 activation, was induced by live but not heat-killed F. tularensis, despite the fact that both forms of the bacterium equally induced the IL-1beta transcript. Our results identified activation of TLR2 and caspase-1 as the two main cellular pathways responsible for the inflammatory response to F. tularensis.

Animals↗

PubMed2006

Molecular characterization of Rickettsia rickettsii infecting dogs and people in North Carolina.

Rocky Mountain spotted fever (RMST) is an important cause of morbidity and mortality in people and dogs in the United States. Disease manifestations are strikingly similar in both species, and illness in dogs can precede illness in people. R. rickettsii has been identified as a Select Agent by the CDC as a Category C priority pathogen by the National Institute of Allergic and Infectious Diseases because it is amenable to use as a bioterror agent. The clinical and temporal relationship of naturally occurring diseases in dogs and people suggests that dogs could serve as sentinels for natural infection and bioterrorist attacks using this organism. Recognizing genetic modifications in naturally occurring disease agents in order to distinguish them from intentionally released agents are priorities put forth by the NIAID. To determine whether the rickettsiae naturally infecting dogs is the same as those that infect persons in a given geographical region, we characterized rickettsial isolates obtained from three dogs and two persons diagnosed with RMSF in North Carolina. Portions of three genes (ompA, rrs, and gltA) amplified by PCR were cloned and sequenced or directly sequenced. Reactions were run in duplicate in forward and reverse directions. Gene sequences were aligned with known sequences deposited in GenBank and with each other. Sequences of the 5' region of the ompA gene were 100% homologous with a tick strain (Bitterroot) of R. rickettsii for all five isolates. Sequences of the rrs gene were 99.8 99.9% homologous with a tick strain (Sawtooth) of R. rickettsii. rrs gene sequences from one dog and the two persons was identical. Sequences of one dog isolate differed from these by one base pair. Sequences from another dog isolate differed by two base pairs. Sequences of the gltA gene are pending. This confirms on a molecular level that R. rickettsii causing naturally occurring RMSF in dogs in North Carolina is highly homologous to R. rickettsii that causes the disease in people in the same region. Sequence data will be deposited in GenBank, thereby providing genetic information regarding naturally occurring R. rickettsii.

Animals↗

PubMed2006

Developing models for patient flow and daily surge capacity research.

Between 1993 and 2003, visits to U.S. emergency departments (EDs) increased by 26%, to a total of 114 million visits annually. At the same time, the number of U.S. EDs decreased by more than 400, and almost 200,000 inpatient hospital beds were taken out of service. In this context, the adequacy of daily surge capacity within the system is clearly an important issue. However, the research agenda on surge capacity thus far has focused primarily on large-scale disasters, such as pandemic influenza or a serious bioterrorism event. The concept of daily surge capacity and its relationship to the broader research agenda on patient flow is a relatively new area of investigation. In this article, the authors begin by describing the overlap between the research agendas on daily surge capacity and patient flow. Next, they propose two models that have potential applications for both daily surge capacity and hospitalwide patient-flow research. Finally, they identify potential research questions that are based on applications of the proposed research models.

Crowding↗

PubMed2005

Dimensions of clinical medicine: an interclerkship program.

BACKGROUND: During the 3rd year of medical school, clerkships provide essential clinical experiences. However, other aspects of patient care may be overlooked during this critical phase of medical education. Faced with the challenge of integrating "orphan" topics central to effective and compassionate medical practice, medical schools have begun to develop interclerkships or intersessions. DESCRIPTION: The Dimensions of Clinical Medicine (DCM) interclerkship series at Creighton University included evidence-based medicine, sexuality in clinical medicine, palliative care, professionalism, cultural sensitivity/awareness, complementary and alternative medicine, bioterrorism, and clinical ethics. Each interclerkship comprises 2 half-day sessions conducted at the end of each clerkship rotation. EVALUATION: Students approved of the interclerkship format and valued the active learning strategies employed in the course. Many students felt the time allotted for each program was excessive. We describe educational issues and practical concerns that are central to an effective intersession program. CONCLUSION: The interclerkship format is a viable approach for incorporating orphan topics into the clinical curriculum.

Clinical Clerkship↗

PubMed2006

Childhood immunization coverage in US states: the impact of state policy interventions and programmatic support.

Although research suggests numerous interventions that can improve immunization coverage (Taskforce on Community Preventive Services, 2000), there is often a gap between policies supported by and public entities. The question for this study is whether the variation in childhood (19 to 35 months) immunization coverage rates across states is related to significant variations in state regulatory regimes that may optimize the benefits of state registries and systems that are designed to improve assessment of immunization practices. Utilizing 2002 data from the CDC and survey data collected from state immunization program officials, we find that financial support for state immunization programs, opt-out state registries, and state-mandated participation in provider quality improvement and assessment programs have positive associations with statewide coverage rates. We also suggest that more active state governmental support for interventions supported by rigorous scientific evaluation will not only improve early childhood immunization coverage, but may also support other public health objectives such as life-time full immunization and improve bioterrorism response planning.

Child, Preschool↗