Potential Uses of the Hantavirus as a Biological Weapon
By Aaron Gluck
The hantavirus is a tale of two strains, separated by time and space. One strain is an Old World version, that though less lethal, plagued soldiers in war for the past century. The other New World Strain, on the other hand, has only been known for the past two decades but is far more lethal than its counterpart. It was not until the discovery of the new, more severe version did people become concerned. The original Hantaan virus was researched as part of a bioweapons program, mostly to know more about the pathogen, but inquires did not cross the line towards weaponization. The American Sin Nombre virus, a more virulent version of Hantaan, appeared to have the possibility of being weaponized because of the early research conducted on the Hantann virus. Concerns have grown recently over the ability of terrorists or others to harness the hantavirus as a bioweapon given its extreme lethality. However, concerns over the weaponization of the hantavirus should be evaluated based on its history, the characteristics of the virus, and whether it is efficient enough to be a part of a coordinated biological attack. Such analysis reveals that, while the hantavirus is deadly, it would not be the first choice to weaponize because of its limitations.
The hantavirus has only recently been identified, though there are indications it has been around for some time. The main effort to identify the hantavirus did not occur until 1993. In May 1993, a young and physically fit Navajo man who was suffering from shortness of breath died rapidly while in a hospital in New Mexico. The death of the healthy Navajo man, who was not in the normal demographic for such a death (the old, young, or compromised immune system) shocked health officials, until similar cases were discovered of otherwise healthy people dying of similar symptoms emerged, one of whom was the Navajo man’s fiancee. According to Dr. James Cheek of the Indian Health Service, if it was not for this coincidence, hantavirus may not have been discovered. Laboratory tests could not pinpoint a known pathogen to account for the severity of the pulmonary failures. An investigation of the neighboring states found similar cases encompassing the Four Corners region (Colorado, New Mexico, Arizona, and Utah) and investigators decided to contact the Center for Disease Control’s (CDC) Special Pathogens Branch. CDC scientists were able to determine it was a specialized virus, calling it the hantavirus, and the disease it caused hantavirus pulmonary syndrome (HPS). After further inquiry, the CDC was able to determine that the hantavirus was a series of viruses, and dubbed the US strain the Sin Nombre virus. With this new discovery, a new pathogen was entered into the system for deadly illnesses.
However, hantavirus only came into the public spotlight during a major outbreak in the United States soon after the Navajo man’s death, but it is linked to previous cases around the world and throughout the US. As it turns out, the hantavirus is not a new disease and is far more widespread than previously suspected in the United States. For example, tissues analysis has revealed that the earliest proven case of hantavirus occurred in Utah in 1959, and has been found in 32 states. Even though an earlier sample has not been found, it is assumed hantavirus has been around for years considering the Navajo have ingrained a disease that has similar characteristics to the hantavirus into their traditional medical beliefs. From 1993 to 2004, there were 362 cases of HPS diagnosed with 132 fatalities in the US alone. However, HPS is also found throughout Latin America. Panama, Brazil, Bolivia, Chile, Paraguay, Uruguay, and Argentina have had reported cases of HPS. From 1993 to 2004, there have been 1548 cases and 252 deaths throughout Latin America. The hantavirus is newly discovered by modern science, but people have lived with it for years previous.
Another area where hantavirus is endemic is the pan Eurasian continent with an alternate strain of hantavirus involving hemorrhagic fever with renal syndrome (HFRS) or nephropathia epidemica (NE). During times of European or Asian conflict, HFRS and NE sickened many people but were not grouped together until the hantavirus outbreak in the US. During World War I, a European version of hantavirus struck German, British, and French troops causing renal disease. Captain W.L. Brown in 1916 suspected that the outbreak of “trench nephritis” was extremely similar to the epidemic of renal disease Americans experienced in the American Civil War during the first periods of trench warfare. In 1952, the Yugoslav Army described a disease that struck their soldiers, giving way to the first signs of HFRS in the Balkans. Despite being prevalent in Europe, it was not until the Korean War that scientists started drawing links to the hantavirus. During that time American doctors came into contact with a disease that made approximately 3,000 United Nations troops ill due to acute renal failure, hemorrhages, and sometimes shock. The precursor disease was called Hantaan (HTN; also known as Korean hemorrhagic fever, KHF), after the river where most of the cases were by Dr. Lee in 1977. With Dr. Lee’s findings, other cases were linked to HTN, especially in the 1990s when soldiers in Germany and combatants in Bosnia were sickened with a similar disease. After the 1993 outbreak in the US, the various cases of HFRS and NE were linked as a different strain of hantavirus.
Hantavirus’ biological warfare history is primarily associated with the outbreak of Korean hemorrhagic fever. Because HTN occurred during a military operation, the US Army Medical Research Institute for Infectious Diseases (USAMRIID) conducted the main core of research. Since USAMRIID was involved with KHF due to its effects in the field, the main motivation was diagnosing it and learning more about the virus rather than possible weaponization. However, because USAMRIID was involved and conducted the research at Fort Detrick, HTN was grandfathered into the ongoing US bioweapons program. Despite its ability to effect military operations as demonstrated in the field, military studies of hantavirus do not appear to have gone past the research stage.
Characteristics and Method of Action
Hantavirus is a biological agent, specifically a virus. Hantavirus is spread via rodent either from its bite (saliva) or the aerosolization of urine, feces, saliva, or nesting materials with human to human transmission deemed unlikely. It comes in two strains, HPS in the Americas and HFRS throughout the Eurasian supercontinent. Hantavirus is a genus part of the Bunyaviridea family of negative sense single stranded RNA viruses. This means that the hantavirus will enter a host cell and replace itself with a negative strand of messenger RNA (mRNA), so when the mRNA brings the genetic information for reproduction, the virus is reproduced instead of the original host cell’s molecule. As the cell reproduces more hantavirus, the hantavirus kills the host cell and infects others. As this spreads throughout the body, the internal structures fail and can lead to death.
The incubation period for HPS is 4 to 42 days. However, once someone has been exposed to HPS it attacks the pulmonary system (the lungs) with initial symptoms occurring from one to five days after exposure. HPS attacks with four phases in order; the febrile (prodromal period), cardiopulmonary, diuretic, and convalescent stages. The febrile stage lasts between one to twelve days and symptoms include fever, myalgia, headache, dizziness, nausea, vomiting, and diarrhea. Towards the end of the febrile stage, pulmonary edema (accumulation of fluid in the lungs), nonproductive cough and tachypnea take hold. The cardiopulmonary stage occurs for four to twenty-four hours and symptoms include pulmonary edema, hypotension, weakness, delirium, and shock. By this point, the patient usually dies because of hypoxia or circulatory compromise. The diuretic phase sees the resolution of pulmonary edema, shock, and fever. The convalescent phase will see the patient recover for about two months. Because HPS is a fast acting and damaging virus, its lethality is 30-50%, even for healthy individuals outside the “most likely to get sick” demographic.
HFRS acts differently than HPS. HFRS incubation period is between 4 to 42 days, with the symptoms first appearing one to two weeks after exposure. HFRS causes hemorrhagic fever (bleeding disorder) and renal syndrome (kidney failure) with symptoms starting within one to two weeks. The first signs of HFRS are intense headaches, back and abdominal pain, fever, chills, nausea, blurred vision, flushing of the face, inflammation or redness of the eyes, or a rash. As the HFRS progresses, symptoms include the onset of low blood pressure, acute shock, vascular leakage, and acute kidney failure which would lead to severe fluid overload. The fatality rate for HFRS varies on the virus; for Hantaan virus its 5-15% while Puulmala is less than 1%. Hantaan and Dobrava are generally more severe than Seoul and Puumala virus, and depending on the infection, the patient can recover in weeks or months. HFRS is also known for attacking healthy individuals who would not normally get sick.
For both types of hantavirus it is difficult to diagnose and treat. Because both strains have flu-like symptoms, initial diagnosis of HFRS or HPS can be difficult. According to the National Institutes of Health an Albumin blood test, hantavirus specific blood test, complete blood count, complete metabolic panel, kidney and liver function tests, or an x-ray of the chest can reveal hantavirus. However, just as the initial symptoms mimic the flu, certain tests can reveal misleading results and the severity of HPS can result in the rapid onset of death before properly diagnosed. Even if hantavirus is detected, there are no vaccines, and the only available option is supportive care and antivirals. People and objects in direct contact with the patient are supposed to be decontaminated because the ability of the virus to become airborne and infect others. It is extremely important to decontaminate any area hantavirus may survive because it can live for hours or days in cool, moist, confined, and shaded areas. The virus can also be frozen then thawed, and sustain itself for several weeks in water, urine, damp or dry soil. When hantavirus is discovered either from a patient zero or a rodent, it becomes vital to isolate it before it can infect others.
Since hantavirus has no cure and is a deadly disease, there are specific health guidelines researchers and workers need to follow when in the presence of hantavirus infected materials. When scientists are dealing with hantavirus in a lab they are supposed to use a BSL 3 lab with additional precautions that resemble BSL 4 safety if it is considered to be weaponized or aerosolized. A BSL 3 lab are for agents that can be fatal to humans with no treatment. Procedures include restricted access to the lab and agent storage, the lab technician is separated from the virus (such as a glass barrier with glove inserts), and the room’s airflow is going inside the room rather than out (if there is a spill an aerosolized agent does not leave the contaminated zone). A BSL 4 laboratory are for agents where there is no treatment and high risk of infection by any means. Safety procedures are similar to BSL 3 with exception to lab technicians are required to be in protective suits with their own air supply, there are UV lights and showers for decontamination to exit, and the lab has its own air supply. Because hantavirus precautions are high in a lab, if the lab tests show something is infected with hantavirus, the Office of Hazardous Materials Safety has specific guidelines that call for the complete disinfectant of the area and incineration of contaminated items. Because the main source of getting hantavirus is from aerosolization of the virus, a vacuum would only sicken others. Hantavirus, especially HPS, is a troublesome pathogen that calls for extreme measures that are just a step below BSL 4.
The Possibility of Deployment, Weaponization, and Utility of Hantavirus
According to the CDC, hantavirus falls under Category C of the Bioterrorism Agent Categories which means it is an agent that may pose a threat to national security because it is easy to produce, it is easy to spread (deployment method or human to human transmission), or cause an infection that is hard to treat or prevent. This differs from a Category A agent because Category A agents are already considered to pose a threat to national security. Although the hantavirus may pose a threat to national security, the likelihood it would be used as a bioweapon is minimal.
The first criteria for being a useful biological weapon is that hantavirus would have to be easy to produce. To produce hantavirus, a sample must first be taken from the wild or from a lab. Because the disease occurs naturally in rodents, traps could be set to capture a hantavirus carrying mouse. However, it is impossible to tell whether the captured mouse (or mice) is a carrier. Experiments done on deer mice injected with Sin Nombre (the HPS with 50% mortality rate) showed little to no signs of infection. So, even if someone was able to catch hundreds of mice, there would be no apparent way to distinguish if one had hantavirus or not. The only way to distinguish if the right mouse was found is to do laboratory tests. That itself is a problem because the handling of hantavirus is required to be handled in a BSL 3+ laboratory because of the risks it poses to a person handling the virus. A person trying to separate the virus without the proper precautions, such as a terrorist, poses great risk of self-contracting hantavirus. The problems with extracting and isolating hantavirus do not stop there, as scientists with expert knowledge and facilities still have trouble isolating the virus itself. Of the 25 suspected HPS genotypes, only 10 hantavirus’ were able to be found from tissue samples. Even with advance techniques, it still appears difficult to synthesize hantavirus from natural sources.
It would also be hard to obtain a viable sample from a lab. BSL 3 labs have security systems that prevent unauthorized access to and theft of pathogens. Unless a worker became a “mole” or someone forged the security passes, a terrorist or covert agent would not be able to obtain a hantavirus sample from a BSL 3 lab. Another way other than infiltration to get hantavirus would be requesting it as a good from the US to another country. However, it is illegal to ship any hantavirus outside the United States because it is on the Department of Commerce’s Commerce Control List. The other option would be to obtain it from a lab outside the United States. Even though there are no international standards regarding laboratory safety, countries involved in advance biological research (as mentioned before, hantavirus is difficult to find) often follow the World Health Organization guidelines because of the risk certain diseases pose to both their own scientists and their people. Without working in a lab handling hantavirus, getting a strain of hantavirus to produce from a lab would be laborious.
The second category for Category C is a pathogen is easily transmissible either by artificial means or person to person. However, the hantavirus is not transmissible from human to human, leaving the only other possible option being a synthetic means. Because the main means of infection by hantavirus is inhalation of the virus, the best bioweapon would use an aerosol deployment mechanism. If simple sweeping with a broom will cause someone to get sick, then a properly assembled bioweapon with HPS (assuming someone were able to get around production issues) could have disastrous effects. However, the survival of hantavirus in free nature (outside the household) is unknown, and to have a microscope organism such as a virus survive would need a stabilizer. Without knowing how long hantavirus can survive in free nature, it is unknown which stabilizer is necessary to keep the virus alive long enough to launch a successful bioweapons attack.
So far there are two rudimentary ways to make hantavirus into a bioweapon. Both ways are dependent on being able to find a mouse infected with hantavirus. For an immediate effect with an unknown size of attack, a bioterrorist could gather enough infected material (most likely feces) and place it inside a vacuum like device that recycles air without a filter. By creating dust from the infected material, it aerosolizes the virus and forces it into the breathing supply. If placed in a building, a vacuum machine would not seem out of place in a lobby corner. A slower plan would be using the one infected mouse to infect others and release them in the target area, increasing the likelihood that the mouse in the house is a carrier. However, both deployment methods are unpredictable. The vacuum cleaner type device might kill the virus from the force of the air, the heat generated from the device, or the environment might alter its survivability. The problem with releasing infected mice are their movements are not predictable and may not go into a house or may not even be infected. Both ways might have success, but there is not enough known to properly deploy hantavirus as a bioweapon.
The third and strongest point, according to Category C agents, to use hantavirus for a bioweapon is it does not have a cure and is extremely lethal. At first the antiviral ribavirin appeared to have promising results to help treat hantavirus. However, after further trails of ribavirin in a double-blind test there appeared to have no effect at alleviating the disease, eventually leading the government to declare there is no treatment available except for supportive care. Because hantavirus has no cure and HPS has a 50% fatality rate, it would be a good agent to use for a deadly bioweapon attack. If someone was able to find a way to easily obtain HPS and create a means of deployment, a HPS attack would be deadly. However, until more is known about hantavirus, it does not appear it would be a weapon of choice for a bioattack given the innumerable variables and barriers to success outlined above.
Hantavirus is a complex virus that took years to understand. Until a clinic technician noticed a series of unfortunate deaths in the Four Corners area, hantavirus was relatively off the grid. Hantavirus was known to science before the 1993 outbreak, but it was not until HPS was linked to HFRS were there real concerns. It is a virus that does not skip any demographic, is found naturally, and has a 50% mortality rate. These factors frighten some who worry about its use as a bioweapon. However, the complexity of the virus makes it extremely difficult to work with and translate into a weapons grade agent. There are other naturally found pathogens that are easier to synthesize and use without much effort for deployment, making them much more likely to be used as bioweapons. Hantavirus is a disease to be reckoned with, but the worry should be placed more on its natural occurrence than as a means of a coordinated attack.
 Burns, Joe. Hantavirus in California. California Department of Health Services: Vector-Borne Disease Section.
 Number of Cases and Deaths from hantavirus Pulmonary Syndrome (HPS). Pan American Health Organization. 26 April 2004. <http://www.paho.org/English/AD/DPC/CD/hantavirus-1993-2004.htm>.
 Number of Cases and Deaths from hantavirus Pulmonary Syndrome (HPS). Pan American Health Organization. 26 April 2004.
 Clement, Jan P. Hantavirus. Antiviral Research. Volume 57 Issues 1-2. January 2003.
 Hemorrhagic Fever with Renal Syndrome. Center for Disease Control. 22 August 2005.
 Childs, James and Glass, Gregory. Effects of Hantaviral Infection on Survival, Growth and Fertility in Wild Rat (Rattus Norvegicus) Populations of Baltimore, Maryland. Journal of Wildlife Diseases. 25(4). 1989. <http://www.jwildlifedis.org/cgi/reprint/25/4/469.pdf>.
 Monroe, Martha. Genetic Diversity and Distribution of Peromyscus-Borne Hantaviruses in North America. Emerging Infectious Diseases. Volume 5 Number 1. January-March 1999. <http://www.cdc.gov/ncidod/eid/vol5no1/monroe.htm>.
 Valdivieso, Francisca. Neutralizing Antibodies in Survivors of Sin Nombre and Andes Hantavirus Infection. Center for Disease Control. January 2006 <http://www.cdc.gov/ncidod/eid/vol12no01/05-0930.htm>.
 Mertz, Gregory. Placebo-Controlled, Double-Blind Trial of Intravenous Ribavirin for the Treatment of Hantavirus Cardiopulmonary Syndrome in North America. Clinical Infectious Diseases. Vol. 39, No. 9. 1 November 2004 <http://www.jstor.org.proxyau.wrlc.org/stable/pdfplus/4462931.pdf>.
Aaron has a B.A. in International Studies from American University. He has interned at various organizations ranging from the Hudson Institute to the Royal Military Academy in Brussels. His academic travels have taken him to post conflict areas such as the Balkans and Cyprus. His interests include WMD and conventional weapons proliferation, future security issues, and Transatlantic relations.