This is a ten-step process to guide medical personnel in the evaluation and management of intentional outbreaks of unknown origin and etiology. An algorithmic approach is desirable when dealing with the unknown, especially under the austere conditions and chaos expected on the modern battlefield.

1. Maintain an index of suspicion

In the case of chemical or conventional warfare and terrorism, the sinister nature of an attack might be obvious. Victims would likely succumb in close temporal and geographic proximity to a dispersal or explosive device (i.e., clustered in time and space). Complicating discovery of the sinister nature of a biological attack, however, is the fact that bio-agents possess inherent incubation periods. These incubation periods, typically days to even weeks in length, permit the wide dispersion of victims (in both time and space). Moreover, they make it likely that the 'first responder' to a biological attack would not be the traditional first responder (fire, police, and paramedical personnel), but rather medics, primary care physicians, emergency room personnel, and public health officials. In such circumstances, the maintenance of a healthy 'index of suspicion' by a medical provider is imperative if a timely diagnosis is to be made and prompt therapy instituted.

Additionally, with many of the diseases typically regarded as potential weapons, very early intervention is mandatory if a good patient outcome is to be achieved. Anthrax, botulism, plague, and smallpox are readily prevented if patients are provided proper antibiotics, antisera, and/or vaccination promptly after exposure. Conversely, all of these diseases may prove fatal if therapy or prophylaxis is delayed until classic symptoms develop. Unfortunately, symptoms in the early, or prodromal, phase of these illnesses are non-specific, making diagnosis difficult. Moreover, many weaponizable bioagent infections, such as brucellosis, Q fever, and Venezuelan equine encephalitis (VEE), may present simply as undifferentiated febrile illnesses. Without a high index of suspicion, it is unlikely that medical personnel, especially at lower echelons of care, removed from sophisticated laboratory and preventive medicine resources, will promptly arrive at a proper diagnosis and institute appropriate therapy.

2. Protect yourself

Before medical personnel approach a potential biological casualty, they must first take steps to protect themselves. These steps may involve a combination of physical, chemical, and immunologic forms of protection. On the battlefield, physical protection typically consists of a protective mask. Designed primarily with chemical vapor hazards in mind, the M-40 series mask certainly provides adequate protection against all aerosolized bioagent threats. In fact, a HEPA-filter (or even a simple surgical) mask will often afford adequate protection against all bio-agents, although not against chemical threats. Chemical protection refers, in general, to the pre- and/or postexposure administration of antibiotics; such strategies are discussed on an agent-specific basis elsewhere in this book. Immunologic protection principally involves active vaccination and, at present time, applies mainly to protection against anthrax and smallpox. Again, specific vaccination strategies are discussed throughout this book. Obviously, not all of these protective strategies would be applicable in every situation.

3. Assess the patient

This initial assessment is somewhat analogous to the primary survey of ATLS management. As such, before attention is given to specific management, airway adequacy should be assessed and breathing and circulation problems addressed. The initial assessment is conducted before decontamination is accomplished and thus should be brief, but the need for decontamination and for the administration of antidotes for rapid-acting chemical agents (nerve agents and cyanide) should be determined at this time. Historical information of potential interest to the clinician should also be gathered, and might include information about illnesses among other unit members, the presence of unusual munitions, food and water procurement sources, vector exposure, vaccination history, travel history, occupational duties, and MOPP status. Physical exam at this point should concentrate on the pulmonary and neuromuscular systems, as well as any unusual rashes or bleeding.

4. Decontaminate as appropriate

Decontamination plays a very important role in the approach to chemical casualty management. The incubation period of bio-agents, however, makes it unlikely that victims of a biological attack will present for medical care until days after exposure. At this point, the need for decontamination is likely minimal or non-existent. In those rare cases where decontamination is warranted, simple soap and water bathing will usually suffice. Certainly, standard military decontamination solutions (such as hypochlorite), typically employed in cases of chemical agent contamination, will be effective against all bio-agents. In fact, even 0.1% bleach reliably kills anthrax spores, the hardiest of bio-agents. Routine use of caustic substances, especially on human skin, however, is rarely warranted after a biological attack. More information on decontamination is included elsewhere in this text. It must also be kept in mind that a biological attack constitutes a criminal act and that hasty ill-considered decontamination risks destroying valuable evidence.

5. Establish a diagnosis

With decontamination (where warranted) accomplished, a more thorough attempt to establish a diagnosis can be carried out. This attempt, somewhat analogous to the secondary survey used in the ATLS approach, should involve a combination of clinical, epidemiological, and laboratory examinations. The amount of expertise and support available to the clinician will vary at each echelon of care. At higher echelons, a full range of laboratory capabilities might enable prompt definitive diagnoses. At lower echelons, every attempt should be made to obtain diagnostic specimens from representative patients and forward these through laboratory channels. Nasal swabs (important for culture and polymerase chain reaction (PCR), even if the clinician is unsure which organisms are present), blood cultures, serum, sputum cultures, blood and urine for toxin analysis, throat swabs, should be obtained. Environmental samples should also be collected according to established protocols, and analyzed accordingly. In no case, however, should the performance of (or unavailability of) laboratory studies delay empiric diagnosis and therapy.

6. Render prompt treatment

Render prompt treatment. Unfortunately, it is precisely in the prodromal phase of many diseases that therapy is most likely to be effective. For this reason, empiric therapy of pneumonia or undifferentiated febrile illness on the battlefield or in a potential bioterrorism scenario might be indicated under certain circumstances. Table 2 was constructed by eliminating from consideration those diseases for which definitive therapy is not warranted, not available, or not essential. Those that remain, therefore, have some specific (as opposed to merely supportive) therapy available. Empiric treatment of respiratory casualties (patients with undifferentiated febrile illnesses who might have prodromal anthrax, plague, or tularemia would all be managed similarly) might then be entertained. Doxycycline, for example, is effective against most strains of Bacillus anthracis, Yersinia pestis, and Francisella tularensis, as well as against Coxiella burnetii, and the Brucellae. Other tetracyclines and fluoroquinolones might also be considered. Similarly, rapid-onset respiratory casualties might be treated empirically using a cyanide antidote kit, while rapid-onset neurological casualties might warrant prompt empiric therapy with a Nerve Agent Antidote Kit. Keep in mind that such therapy is, in no way, a substitute for a careful and thorough diagnostic evaluation, when conditions permit such an evaluation.

7. Practice good infection control

Standard precautions provide adequate protection against most infectious diseases, including most of those potentially employed in a biological attack. Anthrax, tularemia, brucellosis, glanders, Q fever, VEE, and the toxin-mediated diseases are not generally contagious, and victims can be safely managed using standard precautions. Such precautions should be familiar to all clinicians. Under certain circumstances, however, one of three forms of transmission-based precautions would be warranted. Smallpox victims should, wherever possible, be managed using 'airborne precautions' (including, ideally, a HEPA-filter mask). Pneumonic plague warrants the use of 'droplet precautions' (which include, among other measures, the wearing of a simple surgical mask), and certain viral hemorrhagic fevers and smallpox require 'contact precautions.'

8. Alert the proper authorities

In any military context, the command should immediately be notified of casualties potentially exposed to chemical or bio-agents. The clinical laboratory receiving specimens should also be notified. This will enable laboratory personnel to take proper precautions when handling them and will also permit the optimal use of various diagnostic modalities. Chemical Corps and preventive medicine personnel should be contacted to assist in the delineation of contaminated areas and the search for additional victims.

In a civilian context, such notification would typically be made through local and/or regional health department channels. In the U.S., larger cities often have their own health departments. In most other areas, the county represents the lowest echelon health jurisdiction. In some rural areas, practitioners would access the state health department directly. Once alerted, local and regional health authorities are normally well-versed on the mechanisms for requesting additional support from health officials at higher jurisdictions. Each practitioner should have a point of contact with such agencies and should be familiar with mechanisms for contacting them before a crisis arises.

9. Assist in the epidemiologic investigation and manage the psychological consequences

All healthcare providers should have a basic understanding of epidemiological principles. Even under austere conditions, a rudimentary outbreak investigation may assist in diagnosis and in the discovery of additional biowarfare victims. Clinicians should, at the very least, query patients about illness onset and symptoms, potential exposures, ill unit members, food/water sources, unusual munitions or spray devices, and vector exposures. Early discovery of additional cases through an expedient epidemiologic investigation might, in turn, permit postexposure prophylaxis (PEP), thereby avoiding excess morbidity and mortality. Public health officials would normally conduct more formal and thorough epidemiologic investigations and should be contacted as soon as one suspects the possibility of a biological attack. In a military setting, preventive medicine officers, field sanitation personnel, epidemiology technicians, environmental science officers, and veterinary officers are all available to assist the clinician in conducting an epidemiologic investigation.

In addition to implementing specific medical countermeasures and initiating an epidemiologic investigation, the clinician must be prepared to address the psychological effects of a known, suspected, or feared exposure. Such an exposure (or threat of exposure) can provoke fear and anxiety in the population, and may result in overwhelming numbers of patients seeking medical evaluation. Many of these will likely have unexplained symptoms and many may demand antidotes and other therapies. Moreover, symptoms due to anxiety and autonomic arousal, as well as the side effects of postexposure antibiotic prophylaxis may suggest prodromal disease due to biological-agent exposure, and may pose challenges in differential diagnosis. This 'behavioral contagion' is best prevented by good, proactive, risk communication from health and governmental authorities to community leaders and the media. Such risk communication should include a realistic assessment of the risk of exposure, information about the resulting disease, steps to be taken, and points of contact for suspected exposure. Risk communication must be timely, accurate, consistent, and well-coordinated.

Effective risk communication is predicated upon the pre-existence of thorough risk communication plans and tactical approaches. Similarly, plans must be made to rapidly deploy resources for the initial evaluation and administration of postexposure prophylaxis (ideally decentralized to unit level on the battlefield or to residential areas in a civilian context). Finally, plans must be made to proactively develop patient and contact tracing and vaccine screening tools, to access stockpiled vaccines and medications, and to identify and prepare local facilities and healthcare teams for the care of mass casualties.

10. Maintain proficiency and spread the word

Fortunately, the threats of biological warfare and bioterrorism have remained theoretical ones for most medical personnel. Inability to practice casualty management, however, leads to a rapid deterioration of skills and knowledge. It is imperative that the medic maintains proficiency in dealing with this low-probability, but high-consequence problem. This can be done, in part, by availing oneself of several resources. The USAMRIID (www.usamriid.army.mil) web site provides a wealth of information, including the full text of this handbook, as well as links to many other useful sites. Numerous satellite television broadcasts sponsored by USAMRIID, as well as other video course resources, provide in-depth discussion and training in medical biodefense. CD-ROM training aids are also available, and a field manual (Army FM 8-284) summarizes biowarfare disease management recommendations. Finally, medical personnel, once aware of the threat and trained to deal with it, must ensure that other personnel in their units receive training as well. It is only through ongoing training that personnel will be ready to deal with the threat posed by biological weapons. By familiarizing yourself with the contents of this handbook, you have taken a large step towards such readiness.

Standard Precautions

• Wash hands after patient contact.
• Wear gloves when touching blood, body fluids, secretions, excretions and contaminated items.
• Wear a mask and eye protection, or a face shield during procedures likely to generate splashes or sprays of blood, body fluids, secretions or excretions
• Handle used patient-care equipment and linen in a manner that prevents the transfer of microorganisms to people or equipment.

Use care when handling sharps and use a mouthpiece or other ventilation device as an alternative to mouth-to-mouth resuscitation when practical.
Standard precautions are employed in the care of ALL patients.

Airborne Precautions

Standard Precautions plus:

• Place the patient in a private room that has monitored negative air pressure, a minimum of six air changes/hour, and appropriate filtration of air before it is discharged from the room.
• Wear respiratory protection when entering the room.
• Limit movement and transport of the patient. Place a mask on the patient if they need to be moved.

Conventional Diseases requiring Airborne Precautions: Measles, Varicella, Pulmonary Tuberculosis. Biothreat Diseases requiring Airborne Precautions: Smallpox.

Droplet Precautions

Standard Precaution plus:

• Place the patient in a private room or cohort them with someone with the same infection. If not feasible, maintain at least 3 feet between patients.
• Wear a mask when working within 3 feet of the patient.
• Limit movement and transport of the patient. Place a mask on the patient if they need to be moved.

Conventional Diseases requiring Droplet Precautions: Invasive Haemophilus influenzae and meningococcal disease, drug-resistant pneumococcal disease, diphtheria, pertussis, mycoplasma, GABHS, influenza, mumps, rubella, parvovirus. Biothreat Diseases requiring Droplet precautions: Pneumonic Plague.

B-2 Contact Precautions

Standard Precautions plus:

• Place the patient in a private room or cohort them with someone with the same infection if possible.
• Wear gloves when entering the room. Change gloves after contact with infective material.
• Wear a gown when entering the room if contact with patient is anticipated or if the patient has diarrhea, a colostomy or wound drainage not covered by a dressing.
• Limit the movement or transport of the patient from the room.
• Ensure that patient-care items, bedside equipment, and frequently touched surfaces receive daily cleaning.
• Dedicate use of noncritical patient-care equipment (such as stethoscopes) to a single patient, or cohort of patients with the same pathogen. If not feasible, adequate disinfection between patients is necessary.

Conventional Diseases requiring Contact Precautions: MRSA, VRE, Clostridium difficile, RSV, parainfluenza, enteroviruses, enteric infections in the incontinent host, skin infections (SSSS, HSV, impetigo, lice, scabies), hemorrhagic conjunctivitis.

Biothreat Diseases requiring Contact Precautions: Viral Hemorrhagic Fevers.

Additional resources

For more information, see: Garner JS. Guidelines for Infection Control Practices in Hospitals. Infect Control Hosp Epidemiol 1996;17:53-80.

Personal Protection

Chemical Protective Equipment:

• protective mask

The standard issue mask, the M40

• three sizes available
• protects the face, eyes, and respiratory tract when worn correctly
• employs a single, standard screw-on C2A1 filter element, which incorporates two separate but complementary mechanisms: 1) impaction and adsorption of agent molecules onto ASC Whetlerite carbon filtration medium, and 2) static electrical attraction of particles which are able to pass carbon filtration medium on first pass

Proper maintenance and periodic replacement of the crucial filter elements is of utmost importance. The filter MUST be replaced when:

• The elements become immersed in water, crushed, cut, or otherwise damaged.
• Excessive breathing resistance is encountered.
• The "ALL CLEAR" signal is given after exposure to a bio-agent.
• Thirty days have elapsed in the combat theater of operations (the filters must be replaced every 30 days once opened).
• Supply bulletins indicate lot number expiration.
• So ordered by the unit commander.

The filter element must only be changed in an un-contaminated environment. Two styles of optical inserts for the protective mask are available for personnel requiring visual correction. The wire frame style is considered to be the safer of the two and is more easily fitted into the mask. A prong-type optical insert is also available. A drinking tube on the mask can be used while in a contaminated environment. Note that the wearer should disinfect the canteen and tube by wiping with a 5% hypochlorite solution before use.

• protective gloves

Chemical protective gloves and overboots come in various sizes and are both made from butyl rubber. They may be decontaminated and reissued. The gloves and overboots must be visually inspected and decontaminated as needed after every 12 h of exposure in a contaminated environment. While the protective equipment will protect against bio-agents, it is noteworthy that even standard uniform clothing of good quality affords a reasonable protection against dermal exposure of surfaces covered.

• protective footwear covers
• multipurpose rain/snow/CW overboots (MULO)

Chemical protective gloves and overboots come in various sizes and are both made from butyl rubber. They may be decontaminated and reissued. The gloves and overboots must be visually inspected and decontaminated as needed after every 12 h of exposure in a contaminated environment. While the protective equipment will protect against bio-agents, it is noteworthy that even standard uniform clothing of good quality affords a reasonable protection against dermal exposure of surfaces covered.

Facility considerations

Collective protection by using either a hardened or unhardened shelter equipped with an air filtration unit providing overpressure can protect personnel in a biologically contaminated environment. An airlock ensures that no contamination will be brought into the shelter. In the absence of a dedicated structure, enhanced protection can be afforded within most buildings by sealing cracks and entry ports, and providing air filtration with high efficiency particulate air (HEPA) filters within existing ventilation systems. The key problem is that availability of these shelters can be limited in military situations, costly to produce and maintain, and difficult to deploy. Personnel must be decontaminated before entering the collective protection unit.

Routes of exposure

The inhalational route is the most important route of exposure to bio-agents.

Bio-agents can be dispersed as aerosols from:

• point source disseminations

  Aerosols generated by point-source munitions (i.e., stationary aerosol generator, bomblets, etc.) are more apt to produce ground contamination, but only in the immediate vicinity of dissemination. Point-source munitions leave an obvious signature that may alert the field commander that a BW attack has occurred. Because point-source munitions always leave an agent residue, this evidence can be useful for detection and identification purposes.

• line source disseminations

  Unlike some chemical threats, aerosols of bio-agents disseminated by line source munitions (e.g., sprayed by low-flying aircraft or speedboats along the coast) do not leave hazardous environmental residue (although anthrax spores may persist and could pose a hazard near the dissemination line).

Inhalation

Aerosol delivery systems for bioagents most commonly generate invisible clouds with particles or droplets of < 10 *m. They can remain suspended for extensive periods. The major risk in such an attack is pulmonary retention of inhaled particles. To a much lesser extent, some particles may adhere to an individual or his clothing, especially near the face. The effective area covered varies with many factors, including wind speed, humidity, and sunlight. In the absence of an effective real-time detection and alarm systems or direct observation of an attack, the first clue may be mass casualties fitting a clinical pattern compatible with one of the bio-agents. This may occur hours, days, or weeks after an attack.

Toxins may cause direct pulmonary effects or be absorbed and cause systemic toxicity. They are frequently more potent by inhalation than by any other route. A unique clinical feature may be seen which is not observed by other routes (e.g., pulmonary edema after SEB exposure). Mucous membranes, including conjunctivae, are also vulnerable to many bioagents. Physical protection is then quite important and the use of full-face masks equipped with small-particle filters, like the chemical protective masks, assumes a high degree of importance.

Ingestion

With reference to force protection, other routes for delivering bio-agents are thought to be less significant than inhalation, but are nonetheless potentially significant. Contamination of food and water supplies, either deliberately or incidentally after an aerosol attack, represents a hazard for infection or intoxication by ingestion. Determination as to whether food and water supplies are free from contamination is always important, and should be made by appropriate preventive medicine authorities in the event of a bioattack.

Mucous membranes and abrasion

Intact skin provides an excellent barrier against most bio-agents -- T-2 mycotoxins are the sole exception, due to their dermal activity. It is also important to consider that, mucous membranes and abrasions, or otherwise damaged integument, can allow for passage of some bioagents, and should therefore be protected in the event of an attack. Physical protection is then quite important and the use of full-face masks equipped with small-particle filters, like the chemical protective masks, assumes a high degree of importance.

The first indication that a biological attack has occurred will most likely be ill patients. Therefore, the timely monitoring of medical surveillance data is critical for detecting a BW attack in time to potentially affect the outcome of those who may have been exposed but who are not yet ill. This approach is called 'detect to treat.'

Detecting a BW attack comprises of a layered system of defense to protect against biological attacks including timely and accurate intelligence, analysis of medical surveillance data, proper use of personal and collective physical protection equipment, use of medical countermeasures (vaccines and other chemoprophylactic measures), post-event deployment of antibiotics and antivirals, and well developed response protocols.

Syndromic surveillance systems, the automated analysis of routinely collected health data, may not detect outbreaks faster than traditional epidemiological surveillance methods. However, these systems may be able to provide information that can assist with the outbreak investigation, situational awareness, tracing the spread of outbreaks and the effectiveness of countermeasures.

Laboratory services are essential. The services have improved tactics, techniques, and procedures to better provide a forward confirmatory testing capability for both environmental samples and clinical specimens. Units like the 520th TAML (Theater Area Medical Laboratory), FDPMU (Forward Deployed Preventive Medicine Unit), and the Air Force FFBAT (Biological Augmentation Team) have been equipped with RT-PCR instruments such as the light-cycler® and RAPID® to provide for genetic analysis of samples that have been collected and tested as presumptively positive. Additionally, these systems have also been installed in the medical laboratories onboard Navy carrier and amphibious ships. These labs as well as CONUS labs test for multiple biomarkers using other technologies such as immunochemical methods. A single positive test provides for a presumptive identification of an agent as false positives are possible with nearly all laboratory tests. Confirming the presence of an agent requires that at least two tests analyzed by different technologies be performed on the sample because the probability of two tests generating false positive results simultaneously is quite low. Three or more positive tests provide definitive confirmation, as does the 'gold standard' of culturing the organism.

Medical surveillance data collection

The development of real-time detection capability for BW agents and pathogens of military significance has become one of the most challenging, high-priority areas of research within the DoD and civilian sectors. Sensors fielded to date provide presumptive results only for a limited number of BW agents. While several systems have been deployed, and several more are in the technology demonstration stage of development, the following systems are currently available:

1. Biological integrated detection system (BIDS)

   The biological integrated detection system (BIDS) is a HMMWV (high mobility multi-purpose wheeled vehicle)-mounted system that concentrates aerosol particles from environmental air, then subjects the particle sample to antibody-based detection schemes for selected agents. It is presently capable of detecting eight BW agents within 45 minutes.

2. Interim biological agent detection system (IBADS)

   The interim biological agent detection system (IBADS) is a semi-automatic version of the BIDS designed for shipboard use. It is capable of detecting the same eight BW agents as the BIDS but within 25 minutes.

3. Portal shield

   Portal shield is an independent aerosol collector capable of detecting up to eight BW agents within 25 minutes using antibody-based detection. It is designed for fixed installations and can be networked and interfaced with chemical warfare sensors.

4. Joint biological point detection system (JBPDS)

   The joint biological point detection system (JBPDS) is designed to detect 10 BW agents. Like the portal shield it can operate as part of a network. It is designed to a have a process time of less than 18 minutes, decreasing to less than 10 minutes in future versions. JBPDS is intended to be used on multiple platforms and by all military services.

5. Dry filter unit (DFU)

   The dry filter unit (DFU) represents a standardized point detection system for biological agent surveillance and is designed to collect aerosolized bio-particulates from ambient air and then subject them for analysis by several complementary technologies including hand-held assays (HHAs), real-time polymerase chain reaction assays (RT-PCR), and other microbiological confirmatory techniques. Samples may be processed at nearby labs or delivered 114 to established high-volume laboratories set up specifically for such purposes. More information is available at http://www.dcfp.navy.mil/cbrd/ca/dfu.htm. There is also a biological weapons agent-sampling (BWAS) kit designed for manual sampling and testing with the HHA.

6. Long-range biological standoff detection system (LRBSDS)

   The long-range biological standoff detection system (LRBSDS) is under development and is designed to provide a first-line biological standoff detection capability; that is a "detect to warn" capability. It will employ an infrared laser to detect aerosol clouds at a standoff distance of up to 30 kilometers. A second-generation system may extend the range to 100 km. This system will be available for fixed-site applications or may be deployable aboard rotary or fixed-winged aircraft. The short-range biological standoff detection system (SRBSDS) is in the research and development phase. It will employ ultraviolet and laser-induced fluorescence to detect biological aerosol clouds at distances of up to 5 kilometers. The information will be used to provide early warning, enhance contamination avoidance efforts, and as a cue for other detection capabilities. These systems do not identify the agent but may indicate an approaching aerosol. The SRBSDS will be designed to differentiate biological aerosols from other non-biological aerosols. Confirmation of a live BW agent or toxin could then be done using the BIDS or a BWAS Kit and a DFU.

7. Hand-held assays

   Hand-held assays are simple one-time-use immunochromatography devices that are very similar to the urine test strips used for home pregnancy tests. These tests provide a yes-no response to the presence of 10 biological agents within 15 minutes. A skilled user may derive a semi-quantitative measure of an agent's presence by the degree of color change. HHAs are currently employed in virtually all fielded military biological detection systems (BIDS, portal shield, DFUs, JBPDS), and are also present in developmental systems. HHAs are quite versatile. They may be used in automated readers or can be read manually. Although reliable, they are designed only for presumptive identification of agents. Samples must subsequently undergo additional testing with complementary technologies before a definitive identification can be made.

8. Joint biological agent identification and diagnostic system (JBAIDS)

   The joint biological agent identification and diagnostic system (JBAIDS), is similar to the ruggedized advanced pathogen identification device (RAPID). Both employ RT-PCR technology to identify BW agents. They are designed as portable, reusable systems capable of confirmatory identification of BW agents and pathogens. The systems rely on technically advanced processes and critical reagents provided through each respective program. The JBAIDS program has a "spiral upgrade" structure to allow for advances in technology, which will lead to decreases in the weight and cube of the system, lessen the technical expertise required to use the system, and lessen the time required to obtain results. The associated critical reagents program will lead to an increase in the number of agents that can be detected.

9. Zebra (Z) chip project

   The Zebra (Z) chip project represents an attempt to develop a comprehensive surveillance network to detect biothreats and emerging diseases. It consists of four elements. These include a Zebra diagnostic platform, which in its present manifestation includes a gene chip (Z-chip). This chip consists of an array of DNA probes designed to detect various gene sequences. When DNA from an unknown infectious agent is placed on the chip, the DNA will adhere to areas where it locates matching sequences. The resulting DNA pattern will reveal the identity of the infectious organism.

The above systems represent an improvement over previous capabilities. However, they provide presumptive tests for a limited number of agents and are still "detect-to-treat" systems rather than the desired "detect-to-warn" systems.

Syndromic surveillance systems

The need to rapidly detect an intentionally caused disease outbreak has prompted a search for faster and more reliable methods for disease surveillance. "Syndromic surveillance" typically refers to the automated analysis of routinely collected health data that are available even before specific diagnoses are made.

The rapid expansion of such surveillance systems in recent years can be attributed to:

1. increasingly available and timely electronic data entered into accessible databases
2. advances in informatics and statistics for data extraction, normalization, and detection of aberrations in temporal or spatial data
3. growing concerns about the threat of epidemics, influenza pandemics, bioterrorism and biowarfare

In many situations, syndromic surveillance systems may not detect outbreaks faster than traditional epidemiological surveillance methods. However, these systems may be able to provide information that can assist with the outbreak investigation, situational awareness, tracing the spread of outbreaks and the effectiveness of countermeasures.

Data that arise from an interaction with the health care system, but do not include confirmed or definitive diagnoses, can include early, non-specific diagnoses, such as "gastroenteritis," or procedures from initial encounters, such as "stool culture." They can be recorded as text in an electronic record, or through codes such as the International Classification of Diseases (ICD) or Current Procedural Terminology (CPT). A chief complaint such as "cough" can be entered in an Emergency Department electronic medical record, or "rash, unknown etiology" entered in a billing database. These data can also include initial impressions from emergency medical personnel on ambulance runs or calls to nurse advice lines or doctor's offices for information. Pre-encounter information obtained about the health of a population before presentation to a health care provider includes over-the-counter pharmacy sales for items such as cough syrup or anti-diarrheal medication. Behavioral changes can be detected in school or work absenteeism rates or internet queries. In general, the closer the data source is to a medical encounter (chief complaints, provider initial impressions, laboratory test orders), the more reliable the information.

To be analyzed for anomalies and compared to expected illness rates, indicator health events must be grouped into syndromes. Most data types, including pharmacy sales and prescriptions, laboratory tests, ambulance runs, chief complaints and diagnostic codes can be grouped into syndromes. Common syndrome groups include respiratory, gastrointestinal, rash, neurological, and febrile illnesses. A syndrome grouping schema based on ICD-9 codes, with an emphasis on bioterrorism detection, is available (www.bt.cdc.gov).

The most commonly promoted use of syndromic surveillance in a bioterrorism or biological warfare context is for early detection of an attack. Timely awareness of an increase in disease incidence can assist in mobilizing resources and potentially decrease associated morbidity and mortality. There are many examples of retrospective studies showing that syndromic surveillance can provide early warning of large community-wide disease outbreaks when compared to traditional disease reporting. Furthermore, it is assumed that such an alert could effect earlier etiologic diagnoses, and early institution of preventive measures such as vaccination and antibiotic prophylaxis, as well as prioritization of these measures to affected communities in time to reduce morbidity and mortality.

The characteristics of an outbreak that make it most likely to be detected by syndromic surveillance are

• narrow distribution of the incubation period
• longer prodrome, 3) absence of a pathognomonic clinical sign that would speed diagnosis
• diagnosis that is dependent on the use of specialized tests that are unlikely to be ordered

Not all biowarfare or terrorism-caused outbreaks will have these characteristics. In addition, early detection may or may not assist with determining whether the outbreak is the result of an intentional biological attack or not. Any disease outbreak must be investigated by appropriate public health officials, and law enforcement will only be involved if evidence arises that points to illegal activity. Early detection alone does not ensure recognition of a biological attack, but data in a syndromic system may help find clues that suggest an intentional event.

Besides early detection, syndromic surveillance systems can assist with the evaluation of the effectiveness of countermeasures, and provide support to epidemiological investigations by finding potential cases that have recently presented and have the same syndromic presentation as those already identified. It can also be used for situational awareness – providing reassurance during periods of high concern such as large public events or when bio-agents have been used on a small scale, such as the anthrax letter attacks, or after the potential ricin exposure in North London. With the use of environmental sensors for bioterrorism detection in large metropolitan areas, potential alerts can be shared with public health officials who can then carefully monitor syndromic data in the same geographic area.

Detect to warn systems

This is an ideal standard that to date has not been fully achieved.

Accurate and timely intelligence is required to develop an effective defense against the use of biological weapons. Once an agent has been dispersed, detecting the biological agent before its arrival over the target (and in time for personnel to don protective equipment), is referred to as "detect to warn." However, the concept of "detect to warn" is an ideal standard that to date has not been fully achieved. Interim systems for detecting dispersed biological agents are just now being fielded in limited numbers.

Other systems in development

There are many other systems under development by the DoD and others. Some employ innovative detection methods such as gene chips and various types of mass spectrometry. Others employ either single or multiple complementary technologies. Some are simply improved aerosol collectors with no inherent BW agent identifying technology. Other government agencies are working on systems similar to portal shield that will use both antibody- and genetic-based detection schemes to yield confirmatory results for both domestic and military use.

Standoff BW agent detection "detect-to-warn" remains a challenging problem and is currently an area of intense research and development. Tomorrow's detectors promise to be faster, more sensitive, and more reliable than those fielded today.

Biological contamination is the introduction of infectious agents to a body surface, food or water, or other inanimate object. In this context, decontamination involves either disinfection or sterilization to reduce microorganisms to a safe level on contaminated articles, thus rendering them suitable for use. Disinfection is the selective reduction of undesirable microbes to a level below that required for transmission. Sterilization is the killing of all organisms.

Methods of decontamination

• Mechanical decontamination

  involves measures to remove but not necessarily neutralize an agent. An example is drinking water filtration to remove certain water-borne pathogens (e.g., Dracunculus medinensis, Naegleria fowleri), or the use of an air filter to remove aerosolized anthrax spores, or soap and water to wash agent from the skin.

• Chemical decontamination

  renders bio-agents harmless by the use of disinfectants that may be a liquid, gas, or aerosol. Factors impacting effectiveness include contact time, solution concentration, composition of the contaminated surface, and characteristics of the agent to be decontaminated. Some disinfectants are harmful to humans, animals, the environment, and/or materiel.

• Physical processes

  (heat, radiation) are other methods that can be employed for decontaminating objects.

Chemical solution preparation

Ampules of calcium hypochlorite (HTH) are currently fielded in the Chemical Agent Decon Set for mixing hypochlorite solutions. Each ampule is six ounces.

Solutions can be made in advance. They should be stored in closed containers. Clearly label all containers.

• 0.5% sodium hypochlorite solution

  A 0.5% sodium hypochlorite solution is made of one part Clorox and nine parts water (1:9) as standard stock Clorox is a 5.25% sodium hypochlorite solution. The solution is then applied with a cloth or swab. The solution should be made fresh daily with the pH in the alkaline range.

• 0.5% hypochlorite solution

  A 0.5% solution can be made by adding 1 - ampule of calcium hypochlorite to 5 gallons of water.

  These solutions evaporate quickly at high temperatures.

• 5% hypochlorite solution

  A 5% solution can be made by adding 8 - ampules of calcium hypochlorite to 5 gallons of water.

  These solutions evaporate quickly at high temperatures.

Patient decontamination

Given the characteristic incubation periods of bio-agents, significant time may have elapsed between the initial exposure and the patients' presentation with illness due to an attack. During this time, external decontamination of any residual agent may have occurred through natural means. Thus, it is only in rare circumstances that patients presenting with illness due to a biological attack will require purposeful external decontamination.

• Dermal exposure

  For dermal exposure to a suspected biological aerosol, immediately and vigorously wash with soap and water. This removes nearly all the agent from the skin surface.

• Gross contamination of skin

  Grossly contaminated skin surfaces(i.e., after the spill of solid or liquid agent from munitions directly onto the skin) should be washed with a 0.5% sodium hypochlorite solution, if available, with a contact time of 10 to 15 min.

  Chlorine solutions must NOT be used in

  1. open body-cavity wounds (as it may lead to the formation of adhesions)
  2. brain and spinal cord injuries
  3. corneal opacities may result from chlorine solution being sprayed into the eyes

  Using a 0.5% sodium hypochlorite solution

  A 0.5% sodium hypochlorite solution is typically used for grossly contaminated exposures.

  Using a 0.5% hypochlorite solution

  In severe circumstances a 0.5% hypochlorite solution may be instilled into non-cavity wounds and then removed by suction to an appropriate disposal container. Within about 5 m, this contaminated solution will be neutralized and non-hazardous. Copious irrigation with saline or other surgical solutions should be subsequently performed.

  Using a 5% hypochlorite solution

  If reaerosolization of agent is a concern due to the presence of gross contaminant, a damp cloth or towel should be placed directly over the area and a 5% solution of hypochlorite (or equivalent disinfectant) should be liberally applied to saturate the gross contaminant. The saturated fabric/bio-agent should then be properly disposed of per established protocol.

Decontaminating fabrics

Use a 5% hypochlorite solution. Fabrics will be damaged with this concentration of hypochlorite.

Decontaminating equipment

There are three main methods of decontaminating equipment.

• Chemical decontamination

  Use a 5% hypochlorite solution with a contact time of 30 min. before normal cleaning is required. This is corrosive to most metals, so rinse thoroughly and oil metal surfaces after completion.

• Sterilization - heat / radiation

  Bio-agents may be rendered harmless through such physical means as heat and radiation. Agents are rendered completely harmless by sterilization with dry heat for 2 h at 160°C.

• Autoclaving

  If autoclaving with steam at 121°C and 1 atmosphere of overpressure (15 psi), the time may be reduced to 20 min, depending on volume.

Solar UV radiation

Solar UV radiation has a disinfectant effect, often in combination with drying. This is effective in certain environmental conditions but is hard to standardize for practical usage for decontamination purposes.

Decontaminating rooms

Rooms in fixed spaces are best decontaminated with aerosolized gases or liquids (e.g., formaldehyde). This is usually combined with surface disinfectants to ensure complete effectiveness.

Decontaminating open spaces

The health hazards of environmental contamination by bio-agents differ from those of persistent or volatile chemical agents. Aerosolized particles in the 1-5 µm size range will remain suspended by brownian motion and can disseminate widely. Suspended bio-agents would be eventually inactivated by solar UV light, desiccation, and oxidation. Little, if any environmental residues would remain. Possible exceptions include residue near the dissemination line or in the immediate area surrounding point-source munitions. Bio-agents deposited on the soil would be subject to degradation by environmental stressors and competing soil microflora. Simulant studies suggest that secondary reaerosolization would be difficult, but may pose a human health hazard. Environmental decontamination of terrain is costly and difficult. If grossly contaminated terrain, streets, or roads must be passed, the use of dust-binding spray to minimize reaerosolization may be considered. If it is necessary to decontaminate these surfaces, chlorine-calcium or lye may be used. Otherwise, rely on the natural processes that, especially outdoors, lead to the decontamination of agent by drying and solar UV radiation.

Additional resources

For further information on decontamination, see FM 3-5, NBC Decontamination; FM 4-02.7, Health Service Support in a NBC Environment; and Army FM 8-284, Treatment of Biological Warfare Agent Casualties.

Electronic copies of all DoD publications are available at the Defense Technical Information Center (DTIC), http://www.dtic.mil/dtic.