Crisis Standard Needed for Anthrax Medical Countermeasure Screening

Mass Dispensing Operations

One of the biggest challenges faced by local public health and emergency preparedness personnel during an anthrax incident is the mass dispensing of postexposure prophylaxis (PEP). Antibiotic PEP is very effective at preventing cases of anthrax if initiated before the onset of symptoms. After a wide area release of Bacillus anthracis (the bacterium that causes anthrax), depending on the location, cities or counties may be responsible for providing PEP to hundreds of thousands or millions of people, with individual points of dispensing (PODs) potentially serving tens of thousands. In the wake of a B. anthracis attack, the CDC's Cities Readiness Initiative explicitly states the goal of dispensing initial antibiotic prophylaxis to the entire affected population within 48 hours of the decision to deploy Strategic National Stockpile (SNS) resources.^3,4 Even though SNS warehouses are strategically located across the country, the CDC assumes that it may take as long as 24 hours for these resources to be delivered to local PODs.^5,6 With this limitation, PODs need to be prepared to dispense PEP to their respective populations in less than 24 hours. The incubation period for anthrax can be as short as 1 day, and once symptoms present, the case fatality rate can exceed 50%, even with proper treatment.^7,8 Even under ideal circumstances, any delay in dispensing PEP could be disastrous.

Like clinicians, local health departments will face a severe shortage of resources during a response to an anthrax incident. Local health departments need evidence-based guidance to streamline their dispensing operations and provide the greatest community benefit under the constraint of limited resources (ie, their own “crisis standard of care”). In order to dispense even 10,000 courses of antibiotics in a 24-hour period, a POD needs to average nearly 7 doses dispensed per minute. The CDC estimates “baseline small POD” throughput at 500 people per hour,^5,6 so larger PODs could easily see thousands of people each hour. POD operations are often conducted using volunteers or partners in both the public and private sectors, as most local health departments cannot provide sufficient manpower to fully staff PODs on their own. POD staff—many of whom have limited, if any, medical training—need to conduct rapid (on the order of seconds, not minutes) assessments of each person for potentially serious, even life-threatening, contraindications to the available prophylaxis in order to reduce the incidence of adverse side effects without unnecessarily delaying dispensing operations. Licensed clinicians are available to address questions and concerns regarding appropriate prophylaxis, but they simply would not have time to deal with each person individually. With limited medical expertise available, PODs need guidance that enables the untrained staff to address the vast majority of the community, reserving the limited medical expert resources to handle only the more complex cases (eg, someone who has contraindications to all of the available PEP options).

With respect to anthrax, the CDC recommends ciprofloxacin and doxycycline as first-line PEP antibiotics, and each drug has a corresponding information sheet that lists a number of contraindications, including drug interactions, preexisting conditions, comorbidities, pregnancy, and age. The risk of some of these contraindications may be lower than the risk of anthrax after a bioterrorist attack, and implementing a simplified “crisis standard of care” screening model could better standardize POD screening processes and increase throughput while still limiting severe adverse side effects. Under normal circumstances, a doctor would compare each drug's information sheet against each patient's medical record to identify potential adverse effects and determine the best option. During mass dispensing operations, however, the time and manpower required to do this would slow dispensing to a crawl, placing thousands of people at increased risk. A simplified screening process would allow untrained volunteers to identify potential contraindications quickly based on limited information and rapidly dispense the appropriate antibiotics. Complex cases would receive individual medical consultation, addressing their particular issue without delaying the dispensing process for anyone else. By making the most of limited screening and dispensing resources and medical expertise while still identifying and addressing the most serious contraindications, PODs can provide the greatest overall public benefit.

Currently, state and local health officials and clinicians develop their own screening protocols for PEP. Because there is no standard recommendation from the CDC, individual jurisdictions may differ in their interpretation of drug safety information or their assessment of the risk due to contraindications relative to anthrax. A cursory internet search identified several jurisdictions that publish their anthrax antibiotic screening process.^9-12 All ask about allergies to ciprofloxacin and doxycycline (as well as other drugs in those classes), pregnancy, and age; however, there are numerous differences among the remaining screening questions. Minnesota does not ask about seizures or epilepsy, while the rest do. Of the 4 juisdictions examined, only the San Francisco Bay Area asks specifically about myasthenia gravis. Minnesota and Oregon ask about the ability to swallow pills, but Clark County (WA) and San Francisco do not. Minnesota and Clark County ask about kidney disease/failure or dialysis; San Francisco and Oregon do not. And with respect to drug interactions, Minnesota lists 18 specific drugs, Clark County asks only about “blood thinner” medications, and San Francisco and Oregon both ask only about Tizanidine, a muscle relaxant. As illustrated by these examples, each questionnaire asks a different series of questions, prioritizing different risks due to contraindications.

As was seen with the 2001 anthrax letters, differences in response between jurisdictions pose a significant problem, both to the health of the exposed population and their trust in public health officials.^13-15 If someone in one jurisdiction could not receive a recommended antibiotic (ciprofloxacin or doxycycline), but they could obtain it in another location, the disparity could seriously hinder the public's trust in public health and preparedness efforts and negatively affect the incident response.

Evidence-Based Guidance

Similar to the updated crisis standard of care clinical guidance, the CDC should commission an evidence-based study on recommended antibiotic screening questions for mass dispensing operations after an anthrax incident in order to standardize this process. For this study, subject matter experts should evaluate existing data and literature to determine the risk of individual contraindications to recommended antibiotic PEP (ie, ciprofloxacin and doxycycline) relative to inhalational anthrax. For example, an allergy or drug interaction could be fatal, but tooth discoloration in children (doxycycline) ¹⁶ or lowering the seizure threshold in epileptic individuals (ciprofloxacin) ¹⁷ may be acceptable compared to inhalational anthrax. Based on these assessments, subject matter experts should develop a recommended screening algorithm for determining the most appropriate PEP antibiotic. In addition to the severity of adverse side effects, this algorithm could account for the expected prevalence of specific contraindications and the composition of antibiotics in SNS Push Packs (ie, the relative quantities of ciprofloxacin and doxycycline and/or the availability of ciprofloxacin oral suspension) to determine the most efficient and effective use of available screening and dispensing resources. For example, if data indicate that there is a high prevalence of a severe contraindication to ciprofloxacin, the screening algorithm would preferentially provide ciprofloxacin to those people without any contraindications in order to reduce the chance of running out of doxycycline.

A consistent, evidence-based screening algorithm would improve POD operations by increasing throughput rates and making the most efficient use of available PEP inventory while ensuring that the limited available medical expertise can be directed to those in the community at the greatest risk for serious complications. Crisis recommendations such as these that are published prior to an event will allow state and local public health and preparedness authorities to develop screening and community education materials well ahead of time rather than devote valuable and limited resources to these tasks in the midst of an incident response. Educational materials could be provided to the public in advance of an incident, as standalone education or as part of broader emergency preparedness efforts, to increase awareness and preparedness in the community. Additionally, familiarity with the screening questions will increase the ability of community members to provide accurate information on their screening forms—or even have them prepared ahead of time—further reducing delays at PODs and increasing the effectiveness of dispensing operations.

While the clinical response to an anthrax incident addresses individual patients, the public health response has an impact on the community as a whole. The prevention of new anthrax cases through public health mass dispensing operations not only directly affects those people, it decreases the burden on what will certainly be overwhelmed healthcare systems, helping to mitigate the effect of limited clinical resources. Mass dispensing operations after an anthrax incident will almost certainly overwhelm even the best-prepared health departments, and expert “crisis standard” guidance could help optimize available resources to provide the greatest benefit to the most people.