Medical NBC Briefing Series Medical NBC Aspects of Marburg

1. 31 May 2001 1 Medical NBC Briefing SeriesMedical NBC Aspects ofMarburg This presentation is part of a series developed by the Medical NBC Staff at the Office of The Surgeon General for the Army. Technical production has been provided by the Chemical and Biological Defense Information Analysis Center (CBIAC). CBIAC is a Department of Defense Information Analysis Center operated by Battelle Memorial Institute and sponsored by the Defense Technical Information Center (DTIC-AI), Fort Belvoir, VA 22060-6218. This report is a work prepared for the United States Government by Battelle. In no event shall either the United States Government or Battelle have any responsibility or liability for any consequences of any use, misuse, inability to use, or reliance upon the information contained herein, nor does either warrant or otherwise represent in any way the accuracy, adequacy, efficacy, or applicability of the contents hereof. Reference: http://www.ncbi.nlm.nih.gov/ICTVdb/Images/Murphy/marburg.htmThis presentation is part of a series developed by the Medical NBC Staff at the Office of The Surgeon General for the Army. Technical production has been provided by the Chemical and Biological Defense Information Analysis Center (CBIAC). CBIAC is a Department of Defense Information Analysis Center operated by Battelle Memorial Institute and sponsored by the Defense Technical Information Center (DTIC-AI), Fort Belvoir, VA 22060-6218. This report is a work prepared for the United States Government by Battelle. In no event shall either the United States Government or Battelle have any responsibility or liability for any consequences of any use, misuse, inability to use, or reliance upon the information contained herein, nor does either warrant or otherwise represent in any way the accuracy, adequacy, efficacy, or applicability of the contents hereof. Reference: http://www.ncbi.nlm.nih.gov/ICTVdb/Images/Murphy/marburg.htm

2. 31 May 2001 2 Purpose

3. 31 May 2001 3 Outline Background Battlefield Response Medical Response Command and Control Summary References Reference for picture: http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/marbimg.htmReference for picture: http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/marbimg.htm

4. 31 May 2001 4 Background Disease Background Disease Course Summary Signs and Symptoms Diagnosis Treatment Current Situation Weaponization Reference for picture: www.bayonet.netReference for picture: www.bayonet.net

5. 31 May 2001 5 Disease Background RNA viruses Marburg recognized in Germany in 1967 23-29% case mortality rate The viral hemorrhagic fevers are a diverse group of human illnesses that are due to RNA viruses from several different viral families: the Filoviridae, which consists of Ebola and Marburg viruses; the Arenaviridae, including Lassa fever, Argentine and Bolivian hemorrhagic fever viruses; the Bunyaviridae, including various members from the Hantavirus genus, Congo-Crimean hemorrhagic fever virus from the Nairovirus genus, and Rift Valley fever from the Phlebovirus genus; and Flaviviridae, such as Yellow fever virus, Dengue hemorrhagic fever virus, and others. Marburg disease has been identified on several occasions as causing disease in man: three times in Africa, once in Germany, and once in Russia from a laboratory accident. The first recognized outbreak of Marburg disease involved 31 infected persons in Germany and Yugoslavia who were exposed to African green monkeys, with 7 fatalities. It is unclear how easily these filoviruses can be spread from human to human, but spread definitely occurs by direct contact with infected blood, secretions, organs, or semen. The reservoir in nature for these viruses is unknown. The case mortality rate for Marburg virus is 23-25%. Reference for the Russian outbreak is Guerant, Walker and Weller, Tropical Infectious diseases, Churchill Livingston and Co. 1999, p. 1240. The viral hemorrhagic fevers are a diverse group of human illnesses that are due to RNA viruses from several different viral families: the Filoviridae, which consists of Ebola and Marburg viruses; the Arenaviridae, including Lassa fever, Argentine and Bolivian hemorrhagic fever viruses; the Bunyaviridae, including various members from the Hantavirus genus, Congo-Crimean hemorrhagic fever virus from the Nairovirus genus, and Rift Valley fever from the Phlebovirus genus; and Flaviviridae, such as Yellow fever virus, Dengue hemorrhagic fever virus, and others. Marburg disease has been identified on several occasions as causing disease in man: three times in Africa, once in Germany, and once in Russia from a laboratory accident. The first recognized outbreak of Marburg disease involved 31 infected persons in Germany and Yugoslavia who were exposed to African green monkeys, with 7 fatalities. It is unclear how easily these filoviruses can be spread from human to human, but spread definitely occurs by direct contact with infected blood, secretions, organs, or semen. The reservoir in nature for these viruses is unknown. The case mortality rate for Marburg virus is 23-25%. Reference for the Russian outbreak is Guerant, Walker and Weller, Tropical Infectious diseases, Churchill Livingston and Co. 1999, p. 1240.

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7. 31 May 2001 7 Signs and Symptoms - Marburg 3 to 9 day incubation period Sudden onset of back pain, sore throat, muscle pain, headache, and nausea Skin rash (papular or maculopapular), fever, low platelets, gastrointestinal bleeding Rapid progression to jaundice; increased bleeding abnormalities Death from encephalitis, fulminant hepatitis, pulmonary and gastrointestinal hemorrhage Marburg Virus Disease has a 3 to 9 day incubation period, after which victims will experience the sudden onset of back and generalized muscle pain, headache, sore throat and nausea. A papular or macupapular skin rash will subsequently develop, followed by jaundice and the bleeding abnormalities characteristic of VHF. Pulmonary and gastrointestinal hemorrhage will progress to fatal severity, with encephalitis and fulminant hepatitis also likely.Marburg Virus Disease has a 3 to 9 day incubation period, after which victims will experience the sudden onset of back and generalized muscle pain, headache, sore throat and nausea. A papular or macupapular skin rash will subsequently develop, followed by jaundice and the bleeding abnormalities characteristic of VHF. Pulmonary and gastrointestinal hemorrhage will progress to fatal severity, with encephalitis and fulminant hepatitis also likely.

8. 31 May 2001 8 Diagnosis - Clinical Large numbers of individuals in the same geographic area presenting over a short time span Acute onset of fever, muscle pain, and extreme exhaustion Large numbers of individuals in the same geographic area presenting the symptoms of a hemorrhagic fever over a short time span should lead medical providers to suspect the possibility of either a natural outbreak (if the outbreak occurs in an endemic area) or the use of Marburg virus as a biological warfare agent in their list of differential diagnoses. Common presenting complaints are fever, severe muscle pain, and extreme exhaustion. Large numbers of individuals in the same geographic area presenting the symptoms of a hemorrhagic fever over a short time span should lead medical providers to suspect the possibility of either a natural outbreak (if the outbreak occurs in an endemic area) or the use of Marburg virus as a biological warfare agent in their list of differential diagnoses. Common presenting complaints are fever, severe muscle pain, and extreme exhaustion.

9. 31 May 2001 9 Diagnosis - Laboratory Blood and urine tests Requires maximum biosafety laboratory Handling specimens should be with extreme caution and special collection and handling methods must be used The symptoms from Ebola are similar to a number of viruses such as Bolivian Hemorrhagic fever, Argentinean Hemorrhagic Fever, Rift valley fever, Lassa, and Congo-Crimean HF. Virological identification will need to be made at sophisticated laboratory facilities such as those at CDC and USAMRIID for definitive diagnosis. Since these facilities simply don�t exist in the areas where these diseases naturally occur, units planning on operating in these endemic areas may want to make advance arrangements for rapid handling of specimens to insure quick diagnosis. For a definitive diagnosis, specific virologic techniques are used. The presence of urinary protein and blood in the urine is common for Marburg hemorrhagic fever. Specialized biocontainment is required for the safe handling of Marburg virus. If specialized biocontainment facilities are available for handling the virus, virus culture and identification may assist in the definitive diagnosis. Because of the contagious nature of the Marburg virus, special precautions must be observed in the collection, handling, shipping and processing of the samples to prevent any transmission of the disease. Both the Centers for Disease Control and Prevention (CDC, Atlanta, Georgia) and the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID, Frederick, Maryland) have diagnostic laboratories functioning at the highest containment level. Specialized laboratory tests to detect specific antigens or antibodies and/or to isolate the virus in blood specimens are not commercially available. Since the Marburg virus is an extreme biohazard, these tests must be performed under the maximum biosafety containment conditions. Often during the acute illness, ELISA can detect early IgM antibody responses to Marburg virus. Additionally, isolation of the virus in cell cultures and direct visualization by electron microscopy is often successful.The symptoms from Ebola are similar to a number of viruses such as Bolivian Hemorrhagic fever, Argentinean Hemorrhagic Fever, Rift valley fever, Lassa, and Congo-Crimean HF. Virological identification will need to be made at sophisticated laboratory facilities such as those at CDC and USAMRIID for definitive diagnosis. Since these facilities simply don�t exist in the areas where these diseases naturally occur, units planning on operating in these endemic areas may want to make advance arrangements for rapid handling of specimens to insure quick diagnosis. For a definitive diagnosis, specific virologic techniques are used. The presence of urinary protein and blood in the urine is common for Marburg hemorrhagic fever. Specialized biocontainment is required for the safe handling of Marburg virus. If specialized biocontainment facilities are available for handling the virus, virus culture and identification may assist in the definitive diagnosis. Because of the contagious nature of the Marburg virus, special precautions must be observed in the collection, handling, shipping and processing of the samples to prevent any transmission of the disease. Both the Centers for Disease Control and Prevention (CDC, Atlanta, Georgia) and the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID, Frederick, Maryland) have diagnostic laboratories functioning at the highest containment level. Specialized laboratory tests to detect specific antigens or antibodies and/or to isolate the virus in blood specimens are not commercially available. Since the Marburg virus is an extreme biohazard, these tests must be performed under the maximum biosafety containment conditions. Often during the acute illness, ELISA can detect early IgM antibody responses to Marburg virus. Additionally, isolation of the virus in cell cultures and direct visualization by electron microscopy is often successful.

10. 31 May 2001 10 Treatment Quarantine of known cases Supportive care � substantial advanced medical supportive care is necessary Intensive care unit facilities Oxygen Hydration (IV therapy) Ventilation support for severe cases Pain management Avoiding blood-thinning medications including aspirin The isolation of infected patients and minimization of contact with uninfected individuals is imperative in preventing the transmission of Marburg virus. Isolation measures include quarantining infected individuals, using barrier nursing practices, decontaminating contaminated materials, and exercising high-level safety containment of laboratory specimens. There is no specific treatment for Marburg hemorrhagic fever infection. Supportive care is typically required with attention paid to fluid replacement to combat dehydration and maintain the proper electrolyte balance. Aspirin or other blood-thinning medication should not be given to infected individuals.The isolation of infected patients and minimization of contact with uninfected individuals is imperative in preventing the transmission of Marburg virus. Isolation measures include quarantining infected individuals, using barrier nursing practices, decontaminating contaminated materials, and exercising high-level safety containment of laboratory specimens. There is no specific treatment for Marburg hemorrhagic fever infection. Supportive care is typically required with attention paid to fluid replacement to combat dehydration and maintain the proper electrolyte balance. Aspirin or other blood-thinning medication should not be given to infected individuals.

11. 31 May 2001 11 Current Situation Currently endemic in Africa As a biological warfare agent, Marburg poses a significant threat to ground troops Highly transmissible Infectious Lethal Easily dispersible to ground troops as an aerosol Stable in the environment International deployments of US troops Risk of importation/exportation of disease Marburg is endemic in some parts of Africa. An adversary could conceivably may choose Marburg virus as a biological warfare agent because it is a particularly dangerous disease, can infect individuals by aerosol, and has a high mortality rate. U.S. military concerns with the HFs include the risk of troops acquiring the disease while deployed overseas, as well as the risk of importation of one of these diseases. Hemorrhagic fever with renal syndrome (HFRS), for example, still constitutes a significant threat to troops stationed in Korea and Bosnia. The HFs pose a potential threat as biological weapons since (except for Dengue) they can be transmitted via aerosol. They are highly stable in the environment and can cause incapacitating and, in some cases, lethal disease. Marburg is endemic in some parts of Africa. An adversary could conceivably may choose Marburg virus as a biological warfare agent because it is a particularly dangerous disease, can infect individuals by aerosol, and has a high mortality rate. U.S. military concerns with the HFs include the risk of troops acquiring the disease while deployed overseas, as well as the risk of importation of one of these diseases. Hemorrhagic fever with renal syndrome (HFRS), for example, still constitutes a significant threat to troops stationed in Korea and Bosnia. The HFs pose a potential threat as biological weapons since (except for Dengue) they can be transmitted via aerosol. They are highly stable in the environment and can cause incapacitating and, in some cases, lethal disease.

12. 31 May 2001 12 Weaponization Aerosolization Inhalation threat Delivery systems can be simple Spray systems Sub munitions Detonation containers Crop duster or boat Bomblets Aircraft Because of the short latency period from infection to presentation of symptoms, the most likely dissemination method for Marburg virus is by aerosol, with individual exposure by inhalation. Dispersal of viral aerosols will cause respiratory infection. The aerosol clouds could consist of suspended droplets that each contain one to thousands of viral particles. To produce such an aerosol, a relatively simple piece of machinery utilizing fine nozzles is used to spray a suspension of� viral particles. Possible delivery systems include an agricultural sprayer mounted on a truck, agricultural aircraft crop dusters, gallon-size garden sprayers, or fire extinguishers. The successful use of these delivery systems depends entirely on their ability to produce respirable aerosol particles in the correct size range (i.e., less than 5 �m). Releasing the virus by bomblets from missiles or high performance aircraft is another possible delivery method. These delivery systems leave a reservoir of agent and a signature. Meteorological conditions are important for the aerosol clouds to be effective. For maximum effectiveness, the aerosol should remain between 3 and 15 feet above the ground, with a� wind speed between 5 and 25 mph. Conditions usually would be best at daybreak, at sundown, or at night (when solar radiation and temperatures are at a minimum).Because of the short latency period from infection to presentation of symptoms, the most likely dissemination method for Marburg virus is by aerosol, with individual exposure by inhalation. Dispersal of viral aerosols will cause respiratory infection. The aerosol clouds could consist of suspended droplets that each contain one to thousands of viral particles. To produce such an aerosol, a relatively simple piece of machinery utilizing fine nozzles is used to spray a suspension of� viral particles. Possible delivery systems include an agricultural sprayer mounted on a truck, agricultural aircraft crop dusters, gallon-size garden sprayers, or fire extinguishers. The successful use of these delivery systems depends entirely on their ability to produce respirable aerosol particles in the correct size range (i.e., less than 5 �m). Releasing the virus by bomblets from missiles or high performance aircraft is another possible delivery method. These delivery systems leave a reservoir of agent and a signature. Meteorological conditions are important for the aerosol clouds to be effective. For maximum effectiveness, the aerosol should remain between 3 and 15 feet above the ground, with a� wind speed between 5 and 25 mph. Conditions usually would be best at daybreak, at sundown, or at night (when solar radiation and temperatures are at a minimum).

13. 31 May 2001 13 Battlefield Response toMarburg Detect Protect Individual protection Collective protection

14. 31 May 2001 14 Detection Possible methods of detection Detection of agent in the environment Clinical (differential diagnosis) Medical surveillance (coordination enhances detection capability) Diagnosis of Marburg is not presumptive of a BW attack � the disease may be endemic to the area The three general methods of detecting any release of a biological agent are detection of the agent in the environment, clinical diagnosis of the disease caused by the agent, or detection of the increase in the number of patients through DNBI (Disease Non-Battle Injury Reports). The detection capability of the theater is greatly enhanced through the coordination and the training of the various units responsible for detection such as coordination of a medical treatment unit with the 520th Theater Army Medical Laboratory (TAML) for testing procedures of samples from patients possibly exposed to Marburg. A potential biological warfare attack with Marburg is suggested by the appearance of disease in the absence of natural vectors or reservoir hosts. Diagnosis of Marburg is not presumptive of a BW attack. The diseases may be a result of vectors in the area. The three general methods of detecting any release of a biological agent are detection of the agent in the environment, clinical diagnosis of the disease caused by the agent, or detection of the increase in the number of patients through DNBI (Disease Non-Battle Injury Reports). The detection capability of the theater is greatly enhanced through the coordination and the training of the various units responsible for detection such as coordination of a medical treatment unit with the 520th Theater Army Medical Laboratory (TAML) for testing procedures of samples from patients possibly exposed to Marburg. A potential biological warfare attack with Marburg is suggested by the appearance of disease in the absence of natural vectors or reservoir hosts. Diagnosis of Marburg is not presumptive of a BW attack. The diseases may be a result of vectors in the area.

15. 31 May 2001 15 Smart tickets are hand-held point detectors based on antigen capture chromatography. These test are similar to pregnancy tests in that the biological agent chemically binds to the agent-specific antibodies on the test strip, inducing a color change that can be observed by the naked eye. These devices are strictly screening assays, and the analyses are subject to error from the introduction of other contaminants. Therefore, positive results need to be confirmed with more sensitive tests. The Navy Medical Research Institute at Bethesda, Maryland currently produces these instruments. Similar devices have recently become commercially available through Environmental Technologies Corporation. According to the National Research Council�s Chemical and Biological Terrorism (1999), smart tickets are available for Y. pestis, F. tularensis, B. anthracis, V. cholerae, SEB, ricin, botulinum toxins, and Brucella species, but not for hemorrhagic fever viruses. ELISA is a biological assay based on the specificity of the antigen-antibody reaction. These immunoassays are laboratory procedures used to detect specific antibodies that are developed by the body's immune system when the person is exposed to that biological agent. Antibodies can be found in serum or other body fluids from humans, animals, arthropods, or mosquitoes. The 520th TAML and USAMRIID currently operate this system in the field. PCR is a method for synthesizing and amplifying defined sequences of DNA. The PCR process uses temperature to separate the two targeted DNA strands and then reproduce that strand millions of times for detection. The system is currently fielded to the 520th TAML. Since the field of the above equipment and units such as the 520th will greatly vary, the medical NBC officer should keep in close contact with the CINC for the for information on the capability in theater.Smart tickets are hand-held point detectors based on antigen capture chromatography. These test are similar to pregnancy tests in that the biological agent chemically binds to the agent-specific antibodies on the test strip, inducing a color change that can be observed by the naked eye. These devices are strictly screening assays, and the analyses are subject to error from the introduction of other contaminants. Therefore, positive results need to be confirmed with more sensitive tests. The Navy Medical Research Institute at Bethesda, Maryland currently produces these instruments. Similar devices have recently become commercially available through Environmental Technologies Corporation. According to the National Research Council�s Chemical and Biological Terrorism (1999), smart tickets are available for Y. pestis, F. tularensis, B. anthracis, V. cholerae, SEB, ricin, botulinum toxins, and Brucella species, but not for hemorrhagic fever viruses. ELISA is a biological assay based on the specificity of the antigen-antibody reaction. These immunoassays are laboratory procedures used to detect specific antibodies that are developed by the body's immune system when the person is exposed to that biological agent. Antibodies can be found in serum or other body fluids from humans, animals, arthropods, or mosquitoes. The 520th TAML and USAMRIID currently operate this system in the field. PCR is a method for synthesizing and amplifying defined sequences of DNA. The PCR process uses temperature to separate the two targeted DNA strands and then reproduce that strand millions of times for detection. The system is currently fielded to the 520th TAML. Since the field of the above equipment and units such as the 520th will greatly vary, the medical NBC officer should keep in close contact with the CINC for the for information on the capability in theater.

16. 31 May 2001 16 The BIDS and IBAD are field military equipment that detect biological agents and may be deployed in theater. Again, the fielding of such equipment and the medical NBC officer should keep in close contact with the CINC for the information on the capability in theater. The M31E1 Biological Integrated Detection System (BIDS). The BIDS consists of a shelter mounted on a dedicated vehicle and equipped with a biological detection suite that employs complementary technologies to detect large-area biological attacks. The biological detection suite links aerodynamic particle sizing, bioluminescence, flow cytometry, mass spectrometry, and immunoassay technologies in a complementary, layered manner to increase detection confidence. The particle sizing and bioluminescence instrumentation gives the BIDS the ability to determine if an aerosol is of biological material. The agent specific antibody test that can be accomplished by the BIDS is distribution restricted information and can be found in FM 3-101-4 (Biological Detection Platoon Operations Tactics, Techniques, and Procedures). The BIDS is a corps-level asset. The Interim Biological Agent Detector (IBAD) program will provide Naval forces a contingency capability, warning of the presence of biological and toxicological warfare agents. The IBAD is a point detector system designed for shipboard use. It is composed of a particle size counter, particle wet cyclone sampler, and a manual identifier (improved membrane calorimetric ticket flow-through assay). The antibody-antigen tickets are used for BW agent identification in the ship's medical bay. The IBAD probably has similar detection capability as the BIDS. The Navy has a total of 25 rapid prototypes that can be deployed with the fleet on short notice. The same technology is being used in the development of biological detectors for ports and airfields. Reference: Department of Defense. Chemical and Biological Defense Program, Annual Report to Congress, March 2000.The BIDS and IBAD are field military equipment that detect biological agents and may be deployed in theater. Again, the fielding of such equipment and the medical NBC officer should keep in close contact with the CINC for the information on the capability in theater. The M31E1 Biological Integrated Detection System (BIDS). The BIDS consists of a shelter mounted on a dedicated vehicle and equipped with a biological detection suite that employs complementary technologies to detect large-area biological attacks. The biological detection suite links aerodynamic particle sizing, bioluminescence, flow cytometry, mass spectrometry, and immunoassay technologies in a complementary, layered manner to increase detection confidence. The particle sizing and bioluminescence instrumentation gives the BIDS the ability to determine if an aerosol is of biological material. The agent specific antibody test that can be accomplished by the BIDS is distribution restricted information and can be found in FM 3-101-4 (Biological Detection Platoon Operations Tactics, Techniques, and Procedures). The BIDS is a corps-level asset. The Interim Biological Agent Detector (IBAD) program will provide Naval forces a contingency capability, warning of the presence of biological and toxicological warfare agents. The IBAD is a point detector system designed for shipboard use. It is composed of a particle size counter, particle wet cyclone sampler, and a manual identifier (improved membrane calorimetric ticket flow-through assay). The antibody-antigen tickets are used for BW agent identification in the ship's medical bay. The IBAD probably has similar detection capability as the BIDS. The Navy has a total of 25 rapid prototypes that can be deployed with the fleet on short notice. The same technology is being used in the development of biological detectors for ports and airfields. Reference: Department of Defense. Chemical and Biological Defense Program, Annual Report to Congress, March 2000.

17. 31 May 2001 17 Clinical Detection Sudden presentation of High fevers, muscle pain, and extreme exhaustion presenting in groups Rapid progression of symptoms When used as a BW agent of Marburg may manifest itself as high fevers, muscle pain and extreme exhaustion involving groups of individuals. Symptoms will progress rapidly causing the troops to become incapacitated.When used as a BW agent of Marburg may manifest itself as high fevers, muscle pain and extreme exhaustion involving groups of individuals. Symptoms will progress rapidly causing the troops to become incapacitated.

18. 31 May 2001 18 Division medical assets lack the ability to test for Marburg. Once suspected, a sample must be sent to a medical treatment facility or other laboratory for biological testing. Biological samples from affected individuals will be used for both medical and legal reasons. General policies for collecting samples in order to facilitate identification of biological agents are essential. Unit SOP�s should address the collection, handling, and shipping of biological samples. In a possible BW event, the MTF or appropriate receiving lab should be contacted in order to assure proper specimen handling. The laboratory officer has the responsibility of assuring this handling.Division medical assets lack the ability to test for Marburg. Once suspected, a sample must be sent to a medical treatment facility or other laboratory for biological testing. Biological samples from affected individuals will be used for both medical and legal reasons. General policies for collecting samples in order to facilitate identification of biological agents are essential. Unit SOP�s should address the collection, handling, and shipping of biological samples. In a possible BW event, the MTF or appropriate receiving lab should be contacted in order to assure proper specimen handling. The laboratory officer has the responsibility of assuring this handling.

19. 31 May 2001 19 The following assets are possible points of contact for assistance in the handling of biological samples: Corps (or appropriate) Chemical Officer - in charge of NBC defense for the unit. Technical Escort Unit - transportation of suspected biological agents and samples. AFMIC (Armed Forces Medical Intelligence Center) - to obtain medical intelligence of naturally occurring disease or enemy capabilities. 520th TAML (Theater Army Medical Laboratory) - first theatre level laboratory that can provide specific assistance in sample collection and analysis. USAMRIID (U.S. Army Medical Research Institute of Infectious Disease) - Assistance in specimen collection and analysis. Expertise in pathogenesis and treatment. WRAIR (Walter Reed Army Institute of Research) - assistance with diagnostic testing, disease pathogenesis, and treatment of patients with BW illnesses. CDC (Center for Disease Control and Prevention) - expertise with diagnostic testing, sample management, disease pathogenesis, and treatment.The following assets are possible points of contact for assistance in the handling of biological samples: Corps (or appropriate) Chemical Officer - in charge of NBC defense for the unit. Technical Escort Unit - transportation of suspected biological agents and samples. AFMIC (Armed Forces Medical Intelligence Center) - to obtain medical intelligence of naturally occurring disease or enemy capabilities. 520th TAML (Theater Army Medical Laboratory) - first theatre level laboratory that can provide specific assistance in sample collection and analysis. USAMRIID (U.S. Army Medical Research Institute of Infectious Disease) - Assistance in specimen collection and analysis. Expertise in pathogenesis and treatment. WRAIR (Walter Reed Army Institute of Research) - assistance with diagnostic testing, disease pathogenesis, and treatment of patients with BW illnesses. CDC (Center for Disease Control and Prevention) - expertise with diagnostic testing, sample management, disease pathogenesis, and treatment.

20. 31 May 2001 20 The medical officer must be keenly aware of bio-warfare and the identification of the disease in WMD-risk areas. Daily medical disposition reports, specifically those reporting disease non-battle illnesses/injuries, are an invaluable tool in determining whether an event is occurring. Rapid identification of an Marburg outbreak is imperative to reduce mortality among the affected troops. Diligence in reporting symptomatic patients and possible syndromes is the key in medical surveillance. A large number of troops simultaneously presenting with Marburg might signal a biological attack as opposed to a natural outbreak. Natural outbreaks will have an index case and the numbers of patients would build in a normal epidemiological fashion. A BW attack will most likely be completed before the local commander will be aware that it is has taken place. Consequently, when the signs of illness occur that lead one to suspect a BW attack, the first task of the medical officer is to attempt to distinguish between a possible BW attack and a disease outbreak of a natural origin. .The medical officer must be keenly aware of bio-warfare and the identification of the disease in WMD-risk areas. Daily medical disposition reports, specifically those reporting disease non-battle illnesses/injuries, are an invaluable tool in determining whether an event is occurring. Rapid identification of an Marburg outbreak is imperative to reduce mortality among the affected troops. Diligence in reporting symptomatic patients and possible syndromes is the key in medical surveillance. A large number of troops simultaneously presenting with Marburg might signal a biological attack as opposed to a natural outbreak. Natural outbreaks will have an index case and the numbers of patients would build in a normal epidemiological fashion. A BW attack will most likely be completed before the local commander will be aware that it is has taken place. Consequently, when the signs of illness occur that lead one to suspect a BW attack, the first task of the medical officer is to attempt to distinguish between a possible BW attack and a disease outbreak of a natural origin. .

21. 31 May 2001 21 The M40 mask and MOPP suit, gloves, and boots will provide protection against a biological agent attack delivered by the aerosol route. Currently, fielded respirators equipped with standard NBC filter canisters will protect the respiratory system against particles greater than 1-1.5 micrometers in size (mass median diameter). Biological agents are generally released in aerosols of particle size 2-10 microns, for retention in the lungs. While the IPE clothing employed against chemical agents will also protect against biological agents, it is important to note that even standard uniform clothing of good quality affords a reasonable protection against dermal exposure these agents. Protective clothing provides a barrier between a soldier and potentially hazardous agents. The various levels of protective clothing are dependent upon the anticipated presence of the agent. Those casualties unable to continue wearing PPE should be held and/or transported within casualty wraps designed to protect the patient against chemical or biological agent exposure. Addition of a filter blower unit to provide overpressure enhances protection and provides cooling. Note that casualty wraps are designed to protect uninfected conventional casualties, for example gun shot wound, from the agent. They are not designed to protect health care workers from an infected patient.The M40 mask and MOPP suit, gloves, and boots will provide protection against a biological agent attack delivered by the aerosol route. Currently, fielded respirators equipped with standard NBC filter canisters will protect the respiratory system against particles greater than 1-1.5 micrometers in size (mass median diameter). Biological agents are generally released in aerosols of particle size 2-10 microns, for retention in the lungs. While the IPE clothing employed against chemical agents will also protect against biological agents, it is important to note that even standard uniform clothing of good quality affords a reasonable protection against dermal exposure these agents. Protective clothing provides a barrier between a soldier and potentially hazardous agents. The various levels of protective clothing are dependent upon the anticipated presence of the agent. Those casualties unable to continue wearing PPE should be held and/or transported within casualty wraps designed to protect the patient against chemical or biological agent exposure. Addition of a filter blower unit to provide overpressure enhances protection and provides cooling. Note that casualty wraps are designed to protect uninfected conventional casualties, for example gun shot wound, from the agent. They are not designed to protect health care workers from an infected patient.

22. 31 May 2001 22 A dedicated hardened or unhardened shelter equipped with an air filtration unit providing overpressure can offer collective protection (Colpro) for personnel in the biologically-contaminated environment. An airlock ensures that no contamination will be brought into the shelter. All personnel must be decontaminated prior to entering Colpro. 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 within existing ventilation systems. Due to the requirement to continue operations in a contaminated environment, a good deal of medical treatment will likely take place in Colpro. Standard universal precautions should be employed as patients are brought to and treated in the Colpro. Food and water suspected of being contaminated should not be consumed. Non-disposable Contaminated articles can be decontaminated using 0.05% hypochlorite solution (1 tbps. Bleach per gallon of water). Disposable items should be incinerated.A dedicated hardened or unhardened shelter equipped with an air filtration unit providing overpressure can offer collective protection (Colpro) for personnel in the biologically-contaminated environment. An airlock ensures that no contamination will be brought into the shelter. All personnel must be decontaminated prior to entering Colpro. 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 within existing ventilation systems. Due to the requirement to continue operations in a contaminated environment, a good deal of medical treatment will likely take place in Colpro. Standard universal precautions should be employed as patients are brought to and treated in the Colpro. Food and water suspected of being contaminated should not be consumed. Non-disposable Contaminated articles can be decontaminated using 0.05% hypochlorite solution (1 tbps. Bleach per gallon of water). Disposable items should be incinerated.

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24. 31 May 2001 24 Patients with Marburg Virus will not be returning to duty within 72 hours and will require intravenous fluid therapy and possibly respiratory support when they are severely symptomatic. Therefore, evacuation in Echelons I and II should be as soon as assets allow. Patients in Echelons III and IV may have intravenous therapies established and maintained in theater until they return to duty. All severely symptomatic patients should return to CONUS for long term care and follow up as soon as assets allow. Triage categories will vary according to the severity of the illness, available resources, and personnel. All patients presenting classified as Immediate. Since these patients are not expected to recover in the 15 days required in theater, they will be evacuated. Evacuation will be METT-T dependent. The availability of isolation facilities for symptomatic patients must be considered prior to evacuation. Communication with the MTF and CINC Commander will be essential prior to evacuation. Considerations must be made on evacuation based on the availability and resources at the MTFs. If possible, all patients should be evacuated from theater. Communication with MTFs regarding all patients is essential prior to evacuation to prevent disease spread out of theater. Patients may be evacuated using both ground and air evacuation assets with considerable infection control precautions during transport. The potential for spread of the organism is significant. Specialized procedures for evacuation must be considered by the medical officer prior to evacuation of patients. All body fluids are potentially dangerous. The virus is usually transmitted when contaminated blood is handled without protection or when bloody vomitus contacts the unprotected eyes of another individual.Patients with Marburg Virus will not be returning to duty within 72 hours and will require intravenous fluid therapy and possibly respiratory support when they are severely symptomatic. Therefore, evacuation in Echelons I and II should be as soon as assets allow. Patients in Echelons III and IV may have intravenous therapies established and maintained in theater until they return to duty. All severely symptomatic patients should return to CONUS for long term care and follow up as soon as assets allow. Triage categories will vary according to the severity of the illness, available resources, and personnel. All patients presenting classified as Immediate. Since these patients are not expected to recover in the 15 days required in theater, they will be evacuated. Evacuation will be METT-T dependent. The availability of isolation facilities for symptomatic patients must be considered prior to evacuation. Communication with the MTF and CINC Commander will be essential prior to evacuation. Considerations must be made on evacuation based on the availability and resources at the MTFs. If possible, all patients should be evacuated from theater. Communication with MTFs regarding all patients is essential prior to evacuation to prevent disease spread out of theater. Patients may be evacuated using both ground and air evacuation assets with considerable infection control precautions during transport. The potential for spread of the organism is significant. Specialized procedures for evacuation must be considered by the medical officer prior to evacuation of patients. All body fluids are potentially dangerous. The virus is usually transmitted when contaminated blood is handled without protection or when bloody vomitus contacts the unprotected eyes of another individual.

25. 31 May 2001 25 Since Marburg patients would probably not be able to return to duty (RTD) in the normal theater evacuation policy of 15 days, strict interpretation of the doctrine would then call for evacuation. However, since Marburg is contagious, one may want to limit the spread of the virus by imposing a quarantine instead of allowing evacuation. Unlike smallpox, Marburg is already endemic to various parts of the world. Therefore the evacuation of patients is not as large of an issue as it is for smallpox. Before evacuating patients suspected of Marburg, guidance should be sought from the CINC. Consideration for evacuation or quarantine should include the current spread of the disease and the ability of the medical units in the area to treat the sick. If the outbreak is limited to a small area, quarantine would probably be the wisest choice. However, if the disease has already spread throughout the region, then evacuation of the patients should be considered. Because of the problems in transporting Marburg patients, the desirability of avoiding unnecessary contact, and the fact that the treatment is merely supportive, a commander may wish to deploy a suitably equipped hospital forward to treat these patients rather than evacuating them to the theater or COMZ level. Mass casualty incidents my require a quarantine in place rather than evacuation due to the lack of facilities available to receive infected patients. Assets of both medical supplies, equipment, and staff may be required in the containment area. The CINC and the MTF commander should be consulted prior to any mass evacuation or quarantine situation. Reference for evacuation: FM 8-10-6.Since Marburg patients would probably not be able to return to duty (RTD) in the normal theater evacuation policy of 15 days, strict interpretation of the doctrine would then call for evacuation. However, since Marburg is contagious, one may want to limit the spread of the virus by imposing a quarantine instead of allowing evacuation. Unlike smallpox, Marburg is already endemic to various parts of the world. Therefore the evacuation of patients is not as large of an issue as it is for smallpox. Before evacuating patients suspected of Marburg, guidance should be sought from the CINC. Consideration for evacuation or quarantine should include the current spread of the disease and the ability of the medical units in the area to treat the sick. If the outbreak is limited to a small area, quarantine would probably be the wisest choice. However, if the disease has already spread throughout the region, then evacuation of the patients should be considered. Because of the problems in transporting Marburg patients, the desirability of avoiding unnecessary contact, and the fact that the treatment is merely supportive, a commander may wish to deploy a suitably equipped hospital forward to treat these patients rather than evacuating them to the theater or COMZ level. Mass casualty incidents my require a quarantine in place rather than evacuation due to the lack of facilities available to receive infected patients. Assets of both medical supplies, equipment, and staff may be required in the containment area. The CINC and the MTF commander should be consulted prior to any mass evacuation or quarantine situation. Reference for evacuation: FM 8-10-6.

26. 31 May 2001 26 The isolation of infected patients and minimization of contact with uninfected individuals is imperative in preventing the transmission of Marburg virus. Isolation measures include quarantining infected individuals, using barrier nursing practices, decontaminating contaminated materials, and exercising high-level safety containment of laboratory specimens. Marburg can be transmitted by body fluids and aerosol transmission has been documented in animal models. The highest risk for secondary transmission is in the later stages of the disease when viral titers in the body are high and the patients may exhibit vomiting, bloody diarrhea, shock and hemorrhage. These diseases are known to spread in the hospital environment, so extreme care is necessary. Patients should be isolated in a single room with an adjoining anteroom that serves as the only entrance. The anteroom should be stocked with gloves, gowns, disposable aprons and masks for the staff. The patient�s room should ideally have negative air pressure compared with the anteroom and outside hall and strict barrier-nursing techniques should be enforced. Transferring patients may increase the potential for secondary transmission. Marburg Virus are inactivated with routine disinfectant solutions (MMWR Vol. 37, No. S-3, 2/26/88.) In previous outbreaks, simple barrier nursing was sufficient to reduce the health care provider infection rate to zero. Individuals exposed to blood or secretions of infected individuals should immediately wash the exposed skin with soap and water. Eyes should be irrigated with large amounts of saline solution or clean water. A disinfectant solution should be used to decontaminate beds and other exposed surfaces. Prior to incineration, disposable items such as pipettes, gloves, and specimen containers should be placed in a container filled with a disinfectant solution. Nondisposable materials should be soaked in a disinfectant solution before autoclaving or, if they cannot be autoclaved,�they must be cleaned with decontamination solutions such as gluteraldehyde, phenolic disinfectants, or hypochlorite. The virus can also be inactivated by ultraviolet or gamma radiation. Patient remains are handled by the Quartermaster section IAW Joint Pub 4-06.The isolation of infected patients and minimization of contact with uninfected individuals is imperative in preventing the transmission of Marburg virus. Isolation measures include quarantining infected individuals, using barrier nursing practices, decontaminating contaminated materials, and exercising high-level safety containment of laboratory specimens. Marburg can be transmitted by body fluids and aerosol transmission has been documented in animal models. The highest risk for secondary transmission is in the later stages of the disease when viral titers in the body are high and the patients may exhibit vomiting, bloody diarrhea, shock and hemorrhage. These diseases are known to spread in the hospital environment, so extreme care is necessary. Patients should be isolated in a single room with an adjoining anteroom that serves as the only entrance. The anteroom should be stocked with gloves, gowns, disposable aprons and masks for the staff. The patient�s room should ideally have negative air pressure compared with the anteroom and outside hall and strict barrier-nursing techniques should be enforced. Transferring patients may increase the potential for secondary transmission. Marburg Virus are inactivated with routine disinfectant solutions (MMWR Vol. 37, No. S-3, 2/26/88.) In previous outbreaks, simple barrier nursing was sufficient to reduce the health care provider infection rate to zero. Individuals exposed to blood or secretions of infected individuals should immediately wash the exposed skin with soap and water. Eyes should be irrigated with large amounts of saline solution or clean water. A disinfectant solution should be used to decontaminate beds and other exposed surfaces. Prior to incineration, disposable items such as pipettes, gloves, and specimen containers should be placed in a container filled with a disinfectant solution. Nondisposable materials should be soaked in a disinfectant solution before autoclaving or, if they cannot be autoclaved,�they must be cleaned with decontamination solutions such as gluteraldehyde, phenolic disinfectants, or hypochlorite. The virus can also be inactivated by ultraviolet or gamma radiation. Patient remains are handled by the Quartermaster section IAW Joint Pub 4-06.

27. 31 May 2001 27 Infection Control (cont) Chemical toilet All body fluids disinfected Disposable equipment / sharps into rigid containers and autoclaved /incinerated Double-bag refuse-outside bag disinfected Electronic/mechanical equipment can be paraformaldehyde disinfected It should be noted that strict adherence to Contact Precautions has halted secondary transmission in the vast majority of circumstances. VHF patients generally have significant quantities of virus in blood and often other secretions. Special caution must be exercised in handling sharps, needles, and other potential sources of parenteral exposure. Clinical laboratory personnel are also at risk for exposure, and should employ a biosafety cabinet and barrier precautions when handling specimens. Caution should be exercised in evaluating and treating the patient with a suspected VHF. Over-reaction on the part of health care providers is inappropriate and detrimental to both patient and staff, but it is prudent to provide as rigorous isolation measures as feasible. These should include the isolation of the patient and stringent adherence to barrier nursing practices. Medical electronic and mechanical equipment should be chemically sterilized after use, in accordance with appropriate CDC guidelines. Experience has shown that VHF such as Marburg, Ebola, Lassa, and Congo-Crimean HF viruses may be particularly prone to aerosol nosocomial spread. Well-documented secondary infections among contacts and medical personnel who were not parenterally exposed have occurred. Sometimes this occurred when the acute hemorrhagic disease (as seen in CCHF) mimicked a surgical emergency such as a bleeding gastric ulcer, with subsequent exposure and secondary spread among emergency and operating room personnel. Therefore, when a significant suspicion of one of these diseases exists, additional management measures should include: an anteroom adjoining the patient�s isolation room to facilitate putting on and removing protective barriers and storage of supplies; use of a negative pressure room for patient care if available; minimal handling of the body should the patient die, with sealing of the corpse in leak-proof material for prompt burial or cremation.It should be noted that strict adherence to Contact Precautions has halted secondary transmission in the vast majority of circumstances. VHF patients generally have significant quantities of virus in blood and often other secretions. Special caution must be exercised in handling sharps, needles, and other potential sources of parenteral exposure. Clinical laboratory personnel are also at risk for exposure, and should employ a biosafety cabinet and barrier precautions when handling specimens. Caution should be exercised in evaluating and treating the patient with a suspected VHF. Over-reaction on the part of health care providers is inappropriate and detrimental to both patient and staff, but it is prudent to provide as rigorous isolation measures as feasible. These should include the isolation of the patient and stringent adherence to barrier nursing practices. Medical electronic and mechanical equipment should be chemically sterilized after use, in accordance with appropriate CDC guidelines. Experience has shown that VHF such as Marburg, Ebola, Lassa, and Congo-Crimean HF viruses may be particularly prone to aerosol nosocomial spread. Well-documented secondary infections among contacts and medical personnel who were not parenterally exposed have occurred. Sometimes this occurred when the acute hemorrhagic disease (as seen in CCHF) mimicked a surgical emergency such as a bleeding gastric ulcer, with subsequent exposure and secondary spread among emergency and operating room personnel. Therefore, when a significant suspicion of one of these diseases exists, additional management measures should include: an anteroom adjoining the patient�s isolation room to facilitate putting on and removing protective barriers and storage of supplies; use of a negative pressure room for patient care if available; minimal handling of the body should the patient die, with sealing of the corpse in leak-proof material for prompt burial or cremation.

28. 31 May 2001 28 Resource requirements for a large scale Marburg virus outbreak will focus mainly on the need for isolation facilities, intensive care facilities, specialized evacuation assets and supportive therapies. In Echelon I and II, therapy started prior to evacuation to higher Echelons will significantly reduce impact to the medical system and decrease morbidity. Echelon III and above must be prepared to receive patients with severe hemodynamic compromise and to accommodate the need for additional long term (14 days) bed space as well as isolation facilities. The goal of theater assets will be to evacuate severely symptomatic patients to CONUS facilities for long term care. Consequently, Echelon III assets may be heavily taxed. The need for specialized infection control equipment and measures will be essential for forward assets. Command may decide that the risk for evacuation is to great in regards to spread of the disease. The decision to quarantine in place will require significant assets to be moved into the theater of operation. Troop movement will be significantly altered if mass casualties exist after a BW event.Resource requirements for a large scale Marburg virus outbreak will focus mainly on the need for isolation facilities, intensive care facilities, specialized evacuation assets and supportive therapies. In Echelon I and II, therapy started prior to evacuation to higher Echelons will significantly reduce impact to the medical system and decrease morbidity. Echelon III and above must be prepared to receive patients with severe hemodynamic compromise and to accommodate the need for additional long term (14 days) bed space as well as isolation facilities. The goal of theater assets will be to evacuate severely symptomatic patients to CONUS facilities for long term care. Consequently, Echelon III assets may be heavily taxed. The need for specialized infection control equipment and measures will be essential for forward assets. Command may decide that the risk for evacuation is to great in regards to spread of the disease. The decision to quarantine in place will require significant assets to be moved into the theater of operation. Troop movement will be significantly altered if mass casualties exist after a BW event.

29. 31 May 2001 29 Intelligence regarding a Marburg BW event will generally come from medical companies. An aerosol attack may be detected and symptoms will begin to appear in large numbers of people 5 days post-exposure. Medical surveillance and medical intelligence reporting to command levels are the keys to responding to a BW event. Since Marburg patients would probably not be able to return to duty (RTD) in the normal theater evacuation policy of 15 days, strict interpretation of the doctrine would then call for evacuation. However, since Marburg is contagious, one may want to limit the spread of the virus by imposing a quarantine instead of allowing evacuation. Unlike smallpox, Marburg is already endemic to various parts of the world. Therefore the evacuation of patients is not as large of an issue as it is for smallpox. Additional Class VIII supplies, specifically 6404 and ICU items, will be necessary to reduce morbidity and mortality. Supply and evacuation routes will be heavily utilized. An aerosol dissemination has the potential for infecting large numbers of individuals at one time. Significant numbers of patients at one time may present themselves reducing manpower suddenly. Evacuation of all effected individuals will also require additional manpower and specialized assets.Intelligence regarding a Marburg BW event will generally come from medical companies. An aerosol attack may be detected and symptoms will begin to appear in large numbers of people 5 days post-exposure. Medical surveillance and medical intelligence reporting to command levels are the keys to responding to a BW event. Since Marburg patients would probably not be able to return to duty (RTD) in the normal theater evacuation policy of 15 days, strict interpretation of the doctrine would then call for evacuation. However, since Marburg is contagious, one may want to limit the spread of the virus by imposing a quarantine instead of allowing evacuation. Unlike smallpox, Marburg is already endemic to various parts of the world. Therefore the evacuation of patients is not as large of an issue as it is for smallpox. Additional Class VIII supplies, specifically 6404 and ICU items, will be necessary to reduce morbidity and mortality. Supply and evacuation routes will be heavily utilized. An aerosol dissemination has the potential for infecting large numbers of individuals at one time. Significant numbers of patients at one time may present themselves reducing manpower suddenly. Evacuation of all effected individuals will also require additional manpower and specialized assets.

30. 31 May 2001 30 For operations in which biological warfare is considered possible, each case of illness on the battlefield could be attributed to a biological attack; even minor symptoms might be interpreted as the initial signs of an artificially-produced disease. This reaction will significantly burden the medical system. Additionally since Marburg is contagious, soldiers may try to isolate themselves or isolate anyone exhibiting Marburg-like symptoms in a hope to prevent the spread of the disease. Therefore control of panic and misinformation thus assumes a significant role. An education of the threat, together with the implementation of defensive measures, will help to prevent panic. This can be achieved only by adequate preparation (for example, standard operating procedures) and by training prior to such an attack. Many positive defensive measures can be taken prior to, or in anticipation of, this contingency. Food chains and water sources should be protected. The control of rodents and insects should be a hygienic priority. Available biological detection equipment and decontamination equipment should be fielded. Soldiers must be trained in the proper use and rapid deployment of protective equipment. Attention to such preparatory measures will increase confidence and enable the BW threat to be met by reducing the psychological impact. Reference: FM 8-9 pp 2-5 to 2-6. For operations in which biological warfare is considered possible, each case of illness on the battlefield could be attributed to a biological attack; even minor symptoms might be interpreted as the initial signs of an artificially-produced disease. This reaction will significantly burden the medical system. Additionally since Marburg is contagious, soldiers may try to isolate themselves or isolate anyone exhibiting Marburg-like symptoms in a hope to prevent the spread of the disease. Therefore control of panic and misinformation thus assumes a significant role. An education of the threat, together with the implementation of defensive measures, will help to prevent panic. This can be achieved only by adequate preparation (for example, standard operating procedures) and by training prior to such an attack. Many positive defensive measures can be taken prior to, or in anticipation of, this contingency. Food chains and water sources should be protected. The control of rodents and insects should be a hygienic priority. Available biological detection equipment and decontamination equipment should be fielded. Soldiers must be trained in the proper use and rapid deployment of protective equipment. Attention to such preparatory measures will increase confidence and enable the BW threat to be met by reducing the psychological impact. Reference: FM 8-9 pp 2-5 to 2-6.

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