Fatigue during extended contingency operations limits unit operational effectiveness and jeopardizes safety. Stress and fatigue are the primary or secondary cause of a large number of casualties. These factors can become the primary agents of mission failure. For example, 26% of major nonejection accidents in combat aircraft are attributable to failures of attention, and 15% are attributable to fatigue and circadian phenomena. Implementation will reduce accidents involving loss of duty days in active duty personnel involved in continuous operations by 15%.

Malaria is a medical threat to U.S. troops deployed to the tropical regions of Africa, Asia, South and Central America, and the Pacific. In Vietnam, infection rates reached 600 per 1,000 soldiers per year. Current control of malaria depends on prophylactic drugs. An effective vaccine will overcome parasite resistance and reduce the need for troops to take antimalarial drugs. A successful vaccine will overcome the technological barrier of interrupting stages of the parasite exposed to the immune system for a brief period of time.

In the pre-hospital setting of modern battlefields, where 50% of combat deaths are due to hemorrhage, a significant number of lives can be saved by stopping hemorrhage from becoming life-threatening, or by quickly, efficiently, and effectively resuscitating victims following massive blood loss. This DTO develops products which will allow field medics to accomplish both of these goals.

Botulinum toxin is a validated BW threat of high priority. It is a potent protein toxin, highly lethal by aerosol exposure. There are seven distinct serotypes of toxin. The present toxoid vaccine (which includes five serotypes) is in short supply, and there are no drugs available for treatment of botulism poisoning. This effort will lead to the development of a new-generation, recombinant-derived vaccine and drugs effective in the treatment of poisoning. These countermeasures will reduce the BW threat and enhance the operational flexibility of U.S. forces.

Nerve agents are a validated threat to U.S. forces. The proposed work will develop a pretreatment based on genetically engineered human cholinesterase to provide extended protection against a wide spectrum of nerve agents without performance-reducing side effects or the need for extensive post-exposure therapy. Improved prophylaxis for chemical warfare agents deters their use by the enemy and increases the capability of U.S. forces and allies to sustain operational tempo and provide full dimension protection.

Diarrhea affects 20-30% of soldiers deployed OCONUS. ETEC caused 55% of diarrhea cases during Operation Desert Storm/Shield (ODS/S) and was a major problem in Somalia. Shigella caused 19% of the cases of acute diarrhea during ODS/S, and Campylobacter caused 60% of diarrheal illnesses during Cobra Gold. Effective vaccines will overcome antibiotic resistance, enhance strategic mobility, and reduce medical logistics requirements. Success will overcome the technology barrier of enhancing the immune response at the mucosal surface.

Vesicant chemical agents, such as sulfur mustard, are a significant threat to U.S. forces. There are no specific medical countermeasures for blister agents. Medical management of the injuries these agents inflict presently depends on immediate decontamination followed by conventional treatment of the resulting blisters or burns, rather than on specifically designed pretreatment/treatment. This work will yield a vesicant agent countermeasure that will prevent or decrease the severity of injuries, substantially reducing casualties among exposed soldiers and thus the medical logistic burden. Effective countermeasures to the vesicant chemical agents would deter their use and enhance capabilities of U.S. forces to sustain operational tempo.

The ability of even low-power lasers to damage the eye poses an especially relevant threat to military operations. Aviators are acutely vulnerable to laser light effects because of the time-critical nature of many visually guided tasks. The loss of visual sensitivity for as little as a few seconds during a crucial phase in a maneuver can seriously compromise mission readiness.

This initiative provides commanders and health care providers with vital intelligence concerning medical aspects of the operational condition of forces, supplementing the integrated battlefield sensor montage. It also includes a medical equipment ensemble capable of projecting elements of sophisticated medical monitoring and treatment to the farthest ends of the battlefield.

Sources of toxic exposure in the operational environment are numerous and diverse. They include solvents and fuels, smoke produced by fires, complex chemical interactions from occupational exposure, and environmental warfare effects. Current capabilities for operational hazard evaluations involve time-consuming and expensive animal toxicity studies. New, rapid, and less expensive toxic hazard evaluation tools are needed to protect the warfighter from the thousands of hazardous substances associated with and generated by military operations. These tools also will yield essential knowledge of biomarkers to be used in the development of chemical and biological agent detectors and exposure monitors providing real-time field data to support operational decisions. Added benefits of these tools include immediate application to base remediation projects, significant reductions in whole animal toxicity testing, and a more timely process to establish operational exposure standards.

Many combat deaths can be directly attributed to cellular and metabolic derangements following massive hemorrhage or trauma. Often, these cellular or metabolic events begin as cascades manifested days later as severe complications (secondary brain injury, multiple organ failure, etc.) or death. Consequently, products developed under this effort are directed at preventing these delayed complications through more effective initial treatments, drugs, devices, etc. These efforts will result in products which will save lives now lost to combat trauma and severe hemorrhage. This effort will identify, evaluate, and transition initial trauma treatments or products to more effectively abolish or attenuate complications arising from combat trauma.

Malaria is a medical threat to U.S. troops deployed to the tropical regions of Africa, Asia, South and Central America, and the Pacific. Cutaneous and visceral leishmaniasis were the most common chronic infections in Operation Desert Shield/Storm veterans. Novel antiparasitic drugs are required as replacements for standard drugs that have lost antiparasitic effectiveness. Success will depend on solving the technology barrier of overcoming drug resistance.

SEB is a validated BW threat of high priority. It is an incapacitating and potentially lethal biological toxin that can be delivered by either aerosol or oral routes to a target population. Since SEB is also a naturally occurring product of the common bacterium Staphylococcus aureus, the bacterium or toxin can be a serious problem on the battlefield, causing sepsis (blood poisoning) and shock. Deliberate exposure of troops to SEB delivered as a BW agent would significantly reduce mission effectiveness. The development of a vaccine against SEB reduces this threat for the soldier, deters its use as a BW agent, and enhances strategic mobility.

Plague caused by Y. pestis is a validated BW threat of high priority. Bubonic and pneumonic plagues caused by Y. pestis are serious BW threats to the soldier. Plague is a disease of rapid onset and high death rates. The effects of aerosol exposure could be further exacerbated by secondary human-to-human spread from infected personnel. The current plague vaccine is too reactogenic, induces immunity that is short-lived, requires multiple immunizations, and is of unproven efficacy against an aerosol exposure. A new vaccine should protect against parenteral and aerosol exposure, have long-lasting immunity, require only one immunization, and protect against the three different forms of the disease. The combination of prophylactic (vaccine) and therapeutic (antibiotic) treatments will afford the soldier the greatest degree of protection against infection with plague, deter its use as a BW agent, and increase the strategic mobility of U.S. forces.

Encephalomyelitis viruses are important BW threats because of aerosol infectivity and relative stability. Clinical illness associated with VEE, EEE, and WEE includes headache, fever, chills, nausea, vomiting, mental confusion, sleepiness, and sometimes seizures and other neurological signs and symptoms. Mosquito vectors normally transmit these alphaviruses to birds, horses, and humans; however, alphaviruses are very stable when freeze-dried and have the potential to be used as a biological weapon. Safe and effective vaccines are needed to protect soldiers. Current vaccines for alphaviruses causing encephalomyelitis are inadequate. Improved vaccines would decrease the threat of BW and enhance strategic mobility.