Military Infectious Diseases Research Program (MIDRP)

MIDRP Web Site

Mission

The mission of the Military Infectious Diseases Research Program (MIDRP) is to protect the U.S. military against naturally occurring infectious diseases via the development of the U.S. Food and Drug Administration (FDA) approved vaccines, drugs, and diagnostic assays and Environmental Protection Agency (EPA) approved vector control protection systems (to prevent transmission of infections by insects, ticks, etc.).

top

Background and Environment

Infectious diseases historically cause more casualties than enemy fire in deployment to tropical regions. The impact on soldiers ranges from loss of man-days to death and can severely hamper combat effectiveness while increasing the logistical burden for diagnosis, treatment and evacuation.

The Military Infectious Diseases Research Program manages research for the DoD on naturally occurring infectious diseases with a focus on protecting the warfighter through development of vaccines, drugs, diagnostics and vector control. The U.S. military has had notable successes in this undertaking (since World War I, deaths from naturally occurring infections have not exceeded deaths due to combat injury in wartime). MIDRP's role is of continuing importance because diseases such as malaria, dengue, diarrhea and leishmaniasis continue to have an adverse impact on military operations and the health of service members. MIDRP has supported HIV vaccine research and development since 1985 as HIV remains a significant threat to service members deployed overseas and is a major source of regional instability in areas of US force protection. The MIDRP HIV research program is heavily leveraged against efforts of other US government agencies. NIAID is a major partner of MIDRP supported HIV vaccine development activities.

More than 300 MD and PhD level Army, Navy, Air Force, Government Service civilian, and contract investigators lead MIDRP R&D efforts. These research professionals are stationed at major infectious diseases research laboratories in Maryland - the Walter Reed Army Institute of Research, the Naval Medical Research Center, and the United States Army Medical Research Institute of Infectious Diseases - and overseas - Peru, Egypt, Kenya, Thailand, and Indonesia. The U.S. military has stationed uniformed scientists in the tropics for more than 100 years, and itsh active overseas laboratories have been in place for as long as 58 years. Military scientists live and work in the tropics to study the disease threats in naturally affected populations. Countermeasures and candidate solutions are studied through all phases of development including field testing. These military scientists serve as goodwill ambassadors, and contribute to developing health and science infrastructure in these tropical countries. Enduring relationships between tropical DoD facilities and ministries of health, international healthcare facilities, and local healthcare providers and researchers are of great value to the U.S. at a time when diseases such as SARS and avian influenza are potential global threats. The global MIDRP military presence provides a real-time early warning system in the identification and assessment of new and reemerging disease. Data from around the world is collected, analyzed, and immediately disseminated to military leadership and other agencies by the military's DoD Global Emerging Infections Surveillance and Response System (DoD-GEIS) at the Armed Forces Health and Surveillance Center (AFHSC).

The MIDRP's capabilities include basic science (discovery and the knowledge base to develop technological approaches) pre-clinical product optimization, and advanced animal model development. Clinical trials expertise for early FDA Phase 1 testing of drugs and vaccines through large (e.g. 42,000 volunteers for hepatitis A vaccine, and 62,000 volunteers for Japanese encephalitis vaccine) pivotal Phase 3 trials in developing nations is an especially valuable asset of the MIDRP. The DoD also has high containment laboratories, pilot Good Manufacturing Practice (GMP) compliant bioproduction facilities, and FDA regulatory expertise in the U.S. and in many international settings.

top

Goals and Objectives

The Military Infectious Diseases Research Program (MIDRP) has the unique goal of developing and fielding medical products (i.e., vaccines, therapeutics, diagnostics, etc.) to prevent U.S. service members from becoming ill from naturally occurring infectious diseases they may be exposed to while they're deployed far from home. While this mission shares some common research goals with other U.S. government and international research organizations, the U.S. military often has unique needs that are often inadequately addressed by these agencies. The goal of developing a vaccine to prevent malaria, a very important and debilitating disease that can rapidly render a fighting force ineffective, is but one example. The focus of the international community is to develop a malaria vaccine that will prevent death in young children and pregnant women in areas of the world where if they can survive the disease, they will develop some natural immunity. While MIDRP scientists actively support and collaborates in these efforts where the respective goals are similar, the military needs a malaria vaccine that will protect its service members who have no prior natural immunity that will enable them to avoid mission-degrading illness and which is also approved by the U.S. FDA. Preventing death in children and keeping soldiers healthy and effective are very distinct goals requiring significantly different research strategies and products.

Other diseases that can uniquely impact the military which are not addressed by other programs include:

• U.S. FDA approved Adenovirus vaccines to protect military recruits from acute respiratory disease while they're in the unique environment of basic training
• FDA approved HIV/AIDS vaccines to protect the U.S. military against HIV strains found outside the U.S.
• FDA approved rapid diagnostic tests for leishmaniasis (one of many tropical diseases where there is little national interest outside of DoD)

Other research programs focus on diarrhea, a major cause of lost duty days, dengue fever for adult populations, scrub typhus, hemorrhagic fevers and other unusual and potentially deadly viruses found overseas. These are diseases of DoD interest yet minimal research efforts exist within other national research programs that would support use by the military. The MIDRP also develops preventive medicine products to reduce insect and vector-borne disease transmission such as improved repellents suitable for the military operational environment, bednets and other products for preventive medicine officers that enhance their ability to assess disease threats in the field. An example of such a success is DEET. This repellent was developed in collaboration with the USDA, introduced to the public in the 1950s and has become, by far, the most common repellent used throughout the world today.

top

Key Themes and Messages

As important as the talented researchers, modern facilities and sophisticated equipment are; the MIDRP has successfully developed candidate products from basic science concepts through pilot scale manufacturing and all phases of animal and clinical evaluation. The program particularly excels at "translational research" where new products are moved from the technology base to a level where a commercial partner will take the product on to licensure and marketing to the U.S. military and civilian population. GlaxoSmithKline, sanofi-pasteur, Barr Pharmaceuticals, Pfizer and many other corporations, as well as nonprofit and other governmental organizations such as the gates Foundation, USAID, NIH, continue to confidently partner with the DoD to get products to the commercial market and the U.S. service member. One of the program's major strengths is the recognition by these partners of the DoD's neutrality (lack of profit motive) as it pursues its service mission. The trust that this engenders facilitates collaborations that would not otherwise be contemplated, allowing the sharing of trade secrets and the testing of many promising new technologies. These unique partnerships drive scientific discovery at a pace rarely achieved by the private sector.

The Army is the lead Service of this DoD program and it receives approximately $70 million of appropriated funds annually for infectious diseases research - less than 2 percent of the NIH total spending on infectious diseases and immunology research. The DoD maximizes the use of its limited resources by successfully partnering with other federal agencies, non-governmental organizations, and the pharmaceutical industry to focus on the unique infectious disease research and prevention needs of the U.S. military.

top

Questions and Answers

Q1. Why are infectious diseases a concern to the military?

A1. Infectious diseases continue to impact operational forces. More service members are hospitalized more often for infectious diseases than those who are wounded in combat. Infectious diseases also place a significant burden on the medical logistical system for people requiring treatment or hospital space. The loss of personnel to infectious diseases reduces operational readiness and effectiveness by requiring replacement troops.

Q2. What impacts have infectious diseases had in recent operations?

A2. Cutaneous leishmaniasis, a disease transmitted by sand flies, had a major impact early in Operation Iraqi Freedom. More than 1,700 personnel were diagnosed with this disease, and many had to be evacuated to the United States for treatment, which majorly impacted treatment facilities. The impact of malaria was seen in Vietnam, where 25% of all Army troops suffered with this disease. Malaria remains a militarily-relevant disease as evidenced in 2003 when 44% of 268 Marines conducting a 2-week mission in Liberia were rapidly rendered ineffective due to malaria. About 40 of them were evacuated to the United States for treatment, and 4 developed severe symptoms. Fortunately, no one died from the infections.

Q3. Why does the military need to conduct infectious disease research?

A3. The focus of MIDRP is to develop countermeasures against diseases our deployed military forces will likely encounter. Most of these diseases are not of concern in the United States. Preventing disease is a force multiplier by keeping people healthy and by enhancing readiness. Unfortunately, a major focus in much of the civilian research community is on treating and not preventing these diseases. For many diseases in this program, there are no other directed research efforts to develop preventive countermeasures required by our military. Focus on prevention helps maximize the military's ability to accomplish its mission around the world.

Q4. What are the technical issues with developing medical products?

A4. Developing vaccines and drugs are a challenge - scientists all over the world are still trying to learn the basic biological principles that make them work. Making safe and effective vaccines and drugs as countermeasures for different microorganisms is highly empirical. Vaccine and drug development is also a high-risk, high-cost venture, with most vaccines and drugs failing in human clinical trials. As such, there is a requirement for continued technology development to provide a robust pipeline of new technologies and materials to replace those that have failed.

Q5. Why can't these products be developed faster?

A5. Besides the technical issues, major constraints on making vaccines are the high costs of development and the need to conduct human clinical trials in a safe and acceptable way. The ability to move forward in clinical testing is dependent on demonstrating that the vaccine/drug is safe in both short- and long-term studies. Conducting trials also is impacted by the ability to recruit subjects into the trials and to complete the studies. Compiling, verifying, and analyzing clinical trial results require considerable time. The next required clinical trial is often dependent on completing a previous trial that may take 1 to 4 years to complete, and FDA licensure often takes many months of evaluation after trials are completed.

Q6. What roles do the FDA and EPA play in medical product development?

A6. Therapeutics, vaccines, diagnostic devices (FDA), and certain other products such as insect repellents (EPA) are, by law, regulated by the U.S. government to ensure the products are safe and effective. Safety concerns are the primary driver for the guidelines and processes in place to ensure individuals and the environment are not harmed by the products being developed and marketed. In recent years, the level and complexity of regulatory oversight have increased significantly, resulting in longer development times.

Q7. How helpful are the FDA and EPA?

A7. The FDA and EPA processes allow for open discussion between product developers and regulatory staffs. However, due diligence by the agencies is the primary concern, and any concerns for safety or effectiveness can result in programs being justifiably slowed or stopped until these concerns are eliminated.

Q8. Why does MIDRP have an HIV program?

A8. Congress started the DoD HIV program in 1985. At the time, the impact of HIV on the military was unclear, and with the DoD's history as a vaccine developer, Congress hoped to provide a mechanism to test HIV vaccines within the context of the DoD laboratories. This effort is now being conducted in a partnership with the National Institute of Allergy and Infectious Diseases.

Q9. With many others funding research in these areas, why does the DoD need to conduct this type of research?

A9. As indicated previously, the DoD must protect its forces from diseases that may impact the ability to complete missions. This does not necessarily align with the needs of the public health community where most efforts are directed at reducing mortality rates. For example, the international malaria effort is dedicated to preventing death in children in endemic areas so that they can acquire immunity and lead more productive lives, whereas the U.S. military's goal is to prevent troops from becoming ill. These are very different efforts requiring different technologies.

Q10. What are the contributions of MIDRP?

A10. MIDRP makes contributions in four main areas:

• Drugs: MIDRP has contributed to the development of most synthetic drugs licensed in the United States for the prevention and treatment of malaria. Next-generation antimalarial drugs include tafenoquine and an intravenous formulation of artesunate.
• Diagnostics: MIDRP diagnostic products include fieldworthy devices to diagnose human infections (e.g., scrub typhus) and to determine if insects are carrying infectious agents transmissible to humans (e.g., malaria parasites and West Nile virus).
• Vector Control: Vector control products include personal protective devices (e.g., insect repellents, insecticides, and bed nets) to prevent mosquitoes, ticks, and sand flies from biting service members. Additional products include computer-based systems that identify potential disease-carrying insects.

Q11. Why does MIDRP have an anti-diarrhea program?

A11. Diarrhea continues to be a major problem for deployed personnel. It can cause serious dehydration and crippling disease, which impacts mission accomplishment. Some affected troops are placed on restricted duty or hospitalized for treatment. Historically, some diarrhea outbreaks have resulted in entire units becoming nonoperational.

Q12. What are the program's interactions with outside research efforts/outside funding organizations?

A12. MIDRP has many successful governmental and commercial partnerships such as CRADAs, the Small Business Innovation Research Program, Congressional Special Interest-appropriated funding, and Interagency Agreements. Critical to the development of any vaccine or therapeutic is the involvement of a commercial partner that has the ability to manufacture and market medical products to those who need them. The high cost of product development usually can only be recovered and the product sustained by having a commercial market for the product. In addition, the basic research and concept development for new products involve both academic and governmental research organizations that are critical for intellectual input and for providing critical research capabilities not always available at military laboratories.

Q13. Where can I learn more about MIDRP?

A13. Additional information about MIDRP can be found at https://midrp.amedd.army.mil/.

top