Background: The pandemic potential of influenza A (H5N1) virus is a prominent public health concern of the 21st century.

Objective: To estimate the effectiveness and cost-effectiveness of alternative pandemic (H5N1) mitigation and response strategies.

Design: Compartmental epidemic model in conjunction with a Markov model of disease progression.

Data Sources: Literature and expert opinion.

Target Population: Residents of a U.S. metropolitan city with a population of 8.3 million.

Time Horizon: Lifetime.

Perspective: Societal.

Interventions: 3 scenarios: 1) vaccination and antiviral pharmacotherapy in quantities similar to those currently available in the U.S. stockpile (stockpiled strategy), 2) stockpiled strategy but with expanded distribution of antiviral agents (expanded prophylaxis strategy), and 3) stockpiled strategy but with adjuvanted vaccine (expanded vaccination strategy). All scenarios assumed standard nonpharmaceutical interventions.

Outcome Measures: Infections and deaths averted, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness.

Results of Base-Case Analysis: Expanded vaccination was the most effective and cost-effective of the 3 strategies, averting 68% of infections and deaths and gaining 404 030 QALYs at $10 844 per QALY gained relative to the stockpiled strategy.

Results of Sensitivity Analysis: Expanded vaccination remained incrementally cost-effective over a wide range of assumptions.

Limitations: The model assumed homogenous mixing of cases and contacts; heterogeneous mixing would result in faster initial spread, followed by slower spread. We did not model interventions for children or older adults; the model is not designed to target interventions to specific groups.

Conclusion: Expanded adjuvanted vaccination is an effective and cost-effective mitigation strategy for an influenza A (H5N1) pandemic. Expanded antiviral prophylaxis can help delay the pandemic while additional strategies are implemented.

Primary Funding Source: National Institutes of Health and Agency for Healthcare Research and Quality.

Background: Neuraminidase inhibitors (NAIs) are stockpiled internationally for extended use in an influenza pandemic.

Purpose: To evaluate the safety and efficacy of extended-duration (>4 weeks) NAI chemoprophylaxis against influenza.

Data Sources: Studies published in any language through 11 June 2009 identified by searching 10 electronic databases and 3 trial registries.

Study Selection: Randomized, placebo-controlled, double-blinded human trials of extended-duration NAI chemoprophylaxis that reported outcomes of laboratory-confirmed influenza or adverse events.

Data Extraction: 2 reviewers independently assessed study quality and abstracted information from eligible studies.

Data Synthesis: Of 1876 potentially relevant citations, 7 trials involving 7021 unique participants met inclusion criteria. Data were pooled by using random-effects models. NAI chemoprophylaxis decreased the frequency of symptomatic influenza (relative risk [RR], 0.26 [95% CI, 0.18 to 0.37]; risk difference [RD], –3.9 percentage points [CI, –5.8 to –1.9 percentage points]) but not asymptomatic influenza (RR, 1.03 [CI, 0.81 to 1.30]; RD, –0.4 percentage point [CI, –1.6 to 0.9 percentage point). Adverse effects were not increased overall among NAI recipients (RR, 1.01 [CI, 0.94 to 1.08]; RD, 0.1 percentage point [CI, –0.2 to 0.4 percentage point), but nausea and vomiting were more common among those who took oseltamivir (RR, 1.48 [CI, 1.86 to 2.33]; RD, 1.7 percentage points [CI, 0.6 to 2.9 percentage points]). Prevention of influenza did not statistically significantly differ between zanamivir and oseltamivir.

Limitations: All trials were industry-sponsored. No study was powered to detect rare adverse events, and none included diverse racial groups, children, immunocompromised patients, or individuals who received live attenuated influenza virus vaccine.

Conclusion: Extended-duration zanamivir and oseltamivir chemoprophylaxis appears to be highly efficacious for preventing symptomatic influenza among immunocompetent white and Japanese adults. Extended-duration oseltamivir is associated with increased nausea and vomiting. Safety and efficacy in several subpopulations that might receive extended-duration influenza chemoprophylaxis are unknown.

Background: Effective disaster preparedness requires coordination across multiple organizations. This article describes a detailed framework developed through the BioNet program to facilitate coordination of bioterrorism preparedness planning among military and civilian decision makers.

Methods: The authors and colleagues conducted a series of semistructured interviews with civilian and military decision makers from public health, emergency management, hazardous material response, law enforcement, and military health in the San Diego area. Decision makers used a software tool that simulated a hypothetical anthrax attack, which allowed them to assess the effects of a variety of response actions (eg, issuing warnings to the public, establishing prophylaxis distribution centers) on performance metrics. From these interviews, the authors characterized the information sources, technologies, plans, and communication channels that would be used for bioterrorism planning and responses. The authors used influence diagram notation to describe the key bioterrorism response decisions, the probabilistic factors affecting these decisions, and the response outcomes.

Results: The authors present an overview of the response framework and provide a detailed assessment of two key phases of the decision-making process:

1. pre-event planning and investment and
   
2. incident characterization and initial responsive measures.
   

The framework enables planners to articulate current conditions; identify gaps in existing policies, technologies, information resources, and relationships with other response organizations; and explore the implications of potential system enhancements.

Conclusions: Use of this framework could help decision makers execute a locally coordinated response by identifying the critical cues of a potential bioterrorism event, the information needed to make effective response decisions, and the potential effects of various decision alternatives. Key words: bioterrorism, decision making, organization and administration, regional health planning

This issue of CHP/PCOR's Quarterly Update covers news from the Winter 2008 quarter and includes articles about:

• the Russian Mortality Crisis and the effect of Gorbachev’s anti-alcohol campaign on life expectancy;
• bioterrorism supply chains – how should policymakers be planning for a bioterrorism attack?
• a Research in Brief selection on the phenomenon and effect of Regression toward the Mean in statistical analysis on study findings;
• the use of pedometers and use of human growth hormone in athletes, both widely-covered topics by the media, investigated by CHP/PCOR researchers.

The newsletter also contains various other news items that may be of interest to our readers.

Note to the reader:

The newsletter is fully-navigational. Any text that is surrounded by a dashed box is clickable and will allow the reader to navigate the newsletter more efficiently. The end of each article contains a special symbol (§) that, when clicked, will take the reader back to the table of contents. Please feel free to contact Amber Hsiao with any questions.

Background: A bioterrorism attack with an agent such as anthrax will require rapid deployment of medical and pharmaceutical supplies to exposed individuals. How should such a logistical system be organized? How much capacity should be built into each element of the bioterrorism response supply chain?

Methods: The authors developed a compartmental model to evaluate the costs and benefits of various strategies for preattack stockpiling and postattack distribution and dispensing of medical and pharmaceutical supplies, as well as the benefits of rapid attack detection.

Results: The authors show how the model can be used to address a broad range of logistical questions as well as related, nonlogistical questions (e.g., the cost-effectiveness of strategies to improve patient adherence to antibiotic regimens). They generate several key insights about appropriate strategies for local communities. First, stockpiling large local inventories of medical and pharmaceutical supplies is unlikely to be the most effective means of reducing mortality from an attack, given the availability of national and regional supplies. Instead, communities should create sufficient capacity for dispensing prophylactic antibiotics in the event of a large-scale bioterror attack. Second, improved surveillance systems can significantly reduce deaths from such an attack but only if the local community has sufficient antibiotic-dispensing capacity. Third, mortality from such an attack is significantly affected by the number of unexposed individuals seeking prophylaxis and treatment. Fourth, full adherence to treatment regimens is critical for reducing expected mortality.

Conclusions: Effective preparation for response to potential bioterror attacks can avert deaths in the event of an attack. Models such as this one can help communities more effectively prepare for response to potential bioterror attacks. Key words: bioterror; supply chain; logistics; anthrax; emergency response.

OBJECTIVE: To identify communication needs and evaluate the effectiveness of alternative communication strategies for bioterrorism responses. METHODS: We provide a framework for evaluating communication needs during a bioterrorism response. Then, using a simulation model of a hypothetical response to anthrax bioterrorism in a large metropolitan area, we evaluate the costs and benefits of alternative strategies for communication during a response. RESULTS: Expected mortality increases significantly with increases in the time for attack detection and announcement; decreases in the rate at which exposed individuals seek and receive prophylaxis; increases in the number of unexposed people seeking prophylaxis; and increases in workload imbalances at dispensing centers. Thus, the timeliness, accuracy, and precision of communications about the mechanisms of exposure and instructions for obtaining prophylaxis and treatment are critical. Investment in strategies that improve adherence to prophylaxis is likely to be highly cost effective, even if the improvement in adherence is modest, and even if such strategies reduce the prophylaxis dispensing rate. CONCLUSIONS: Communication during the response to a bioterror attack must involve the right information delivered at the appropriate time in an effective manner from trusted sources. Because the response system for bioterror communication is only fully operationalized once an attack has occurred, tabletop planning and simulation exercises, and other up-front investments in the design of an effective communication strategy, are critical for effective response planning.

A critical question in planning a response to bioterrorism is how antibiotics and medical supplies should be stockpiled and dispensed. The objective of this work was to evaluate the costs and benefits of alternative strategies for maintaining and dispensing local and regional inventories of antibiotics and medical supplies for responses to anthrax bioterrorism. We modeled the regional and local supply chain for antibiotics and medical supplies as well as local dispensing capacity. We found that mortality was highly dependent on the local dispensing capacity, the number of individuals requiring prophylaxis, adherence to prophylactic antibiotics, and delays in attack detection. For an attack exposing 250,000 people and requiring the prophylaxis of 5 million people, expected mortality fell from 243,000 to 145,000 as the dispensing capacity increased from 14,000 to 420,000 individuals per day. At low dispensing capacities (14,000 individuals per day), nearly all exposed individuals died, regardless of the rate of adherence to prophylaxis, delays in attack detection, or availability of local inventories. No benefit was achieved by doubling local inventories at low dispensing capacities; however, at higher dispensing capacities, the cost-effectiveness of doubling local inventories fell from $100,000 to $20,000/life year gained as the annual probability of an attack increased from 0.0002 to 0.001. We conclude that because of the reportedly rapid availability of regional inventories, the critical determinant of mortality following anthrax bioterrorism is local dispensing capacity. Bioterrorism preparedness efforts directed at improving local dispensing capacity are required before benefits can be reaped from enhancing local inventories.

Objectives:

To systematically review the literature about children with anthrax to describe their clinical course, treatment responses, and the predictors of disease progression and mortality.

Data Sources:

MEDLINE® (1966-2005), 14 selected journal indexes (1900-1966) and bibliographies of all retrieved articles.

Review Methods:

We sought case reports of pediatric anthrax published between 1900 and 2005 meeting predefined criteria. We abstracted three types of data from the English-language reports:

Patient information (e.g., age, gender, nationality).

Symptom and disease progression information (e.g., whether the patient developed meningitis).

Treatment information (e.g., treatments received, year of treatment).

We compared the clinical symptoms and disease progression variables for the pediatric cases with data on adult anthrax cases reviewed previously.

Results:

We identified 246 titles of potentially relevant articles from our MEDLINE® search and 2253 additional references from our manual search of the bibliographies of retrieved articles and the indexes of the 14 selected journals. We included 62 case reports of pediatric anthrax including two inhalational cases, 20 gastrointestinal cases, 37 cutaneous cases, and three atypical cases.

Anthrax is a relatively common and historically well-recognized disease and yet rarely reported among children, suggesting the possibility of significant under-diagnosis, underreporting, and/or publication bias. Children with anthrax present with a wide range of clinical signs and symptoms, which differ somewhat from the presenting features of adults with anthrax. Like adults, children with gastrointestinal anthrax have two distinct clinical presentations:

Upper tract disease characterized by dysphagia and oropharyngeal findings.

Lower tract disease characterized by fever, abdominal pain, and nausea and vomiting.

Additionally, children with inhalational disease may have "atypical" presentations including primary meningoencephalitis. Children with inhalational anthrax have abnormal chest roentgenograms; however, children with other forms of anthrax usually have normal roentgenograms. Nineteen of the 30 children (63%) who received penicillin-based antibiotics survived; whereas nine of 11 children (82%) who received anthrax antiserum survived.

Conclusions:

There is a broad spectrum of clinical signs and symptoms associated with pediatric anthrax. The limited data available regarding disease progression and treatment responses for children infected with anthrax suggest some differences from adult populations. Preparedness planning efforts should specifically address the needs of pediatric victims.

Background: Weaponized Bacillus anthracis is one of the few biological agents that can cause death and disease in sufficient numbers to devastate an urban setting.

Objective: To evaluate the cost-effectiveness of strategies for prophylaxis and treatment of an aerosolized B. anthracis bioterror attack.

Design: Decision analytic model.

Data Sources: We derived probabilities of anthrax exposure, vaccine and treatment characteristics, and their costs and associated clinical outcomes from the medical literature and bioterrorism-preparedness experts.

Target Population: Persons living and working in a large metropolitan U.S. city.

Time Horizon: Patient lifetime.

Perspective: Societal.

Intervention: We evaluated 4 postattack strategies: no prophylaxis, vaccination alone, antibiotic prophylaxis alone, or vaccination and antibiotic prophylaxis, as well as preattack vaccination versus no vaccination.

Outcome Measures: Costs, quality-adjusted life-years, life-years, and incremental cost-effectiveness.

Results of Base-Case Analysis: If an aerosolized B. anthracis bioweapon attack occurs, postexposure prophylactic vaccination and antibiotic therapy for those potentially exposed is the most effective (0.33 life-year gained per person) and least costly ($355 saved per person) strategy, as compared with vaccination alone. At low baseline probabilities of attack and exposure, mass previous vaccination of a metropolitan population is more costly ($815 million for a city of 5 million people) and not more effective than no vaccination.

Results of Sensitivity Analysis: If prophylactic antibiotics cannot be promptly distributed after exposure, previous vaccination may become cost-effective.

Limitations: The probability of exposure and disease critically depends on the probability and mechanism of bioweapon release.

Conclusions: In the event of an aerosolized B. anthracis bioweapon attack over an unvaccinated metropolitan U.S. population, postattack prophylactic vaccination and antibiotic therapy is the most effective and least expensive strategy.

The third edition has 120 new articles, among them Artificial nutrition and hydration, Bioterrorism, Cloning, Cybernetics, Dementia, Managed care, and Nanotechnology. Some 200 articles have been extensively revised, and 100 additional articles have new bibliographies. The alphabetical entries address a wide range of topics that raise difficult and important questions. Abortion, genetic screening, female genital mutilation, the right to die, health issues of immigration, and corporate responsibility are but a few. The contributors discuss the issues from many points of view. The abortion article includes sections covering medical perspectives, contemporary ethical and legal aspects, and Jewish, Catholic, Protestant, and Islamic religious perspectives. There are also articles about bioethics in Buddhism, eugenics, health policy, women as health-care professionals, whistle-blowing in health care, and veterinary ethics. All of the articles are signed, and all have bibliographies. Ample cross-references help readers find related useful material. A list of all the articles and a topical outline appear in volume 1. A series of appendixes offers codes, oaths, and directives related to bioethics; additional resources; key legal cases; and an annotated bibliography of literary works that have a medical component. A detailed index helps users find material that may be scattered over numerous entries, such as information about surrogate motherhood.