War and Infectious Disease

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War and Infectious Disease

Introduction

Throughout history, war epidemics have sapped and destroyed the ability of armies to fight, halted military operations, and brought death and disaster to the civilian populations of the warring factions as well as non-belligerent states. The historical occurrence and geographical spread of infectious diseases associated with wars raises the question of how the distribution of disease in epidemics is influenced by military operations. Historically, epidemics have been associated with military mobilization and the bringing together of tens and even hundreds of thousands of individuals into close quarters and contact in camps and garrisons. Deployment to parts of the world in which diseases are endemic, emerging, or re-emerging expose troops to diseases for which they have no immunity. Lastly, there is the age-old and familiar association of soldiers with prostitutes harboring sexually transmitted diseases. While the history of the impact of war on the emergence and spread of epidemics is long and tragic, this article will be focused on a few instances that bear on contemporary public health issues.

History and Scientific Foundations

The 1918 Influenza Pandemic and World War I

In view of contemporary concerns about the recurrence of a worldwide bird flu pandemic, the association of World War I with the first known avian influenza pandemic is of particular interest. With the possible exception of the ultimate death toll of the AIDS pandemic, which has unfolded over more than a quarter of a century, the 1918–1919 influenza pandemic killed more people than any other outbreak of disease in human history. Estimates of the death toll range from a low of 21 million to a more recent and well-supported estimate of 50 to 100 million dead. At the time of the epidemic, the world population was only 28% of what it is currently, and the majority of the deaths occurred during a sixteen-week period, from mid-September to mid December of 1918.

The origin of the 1918 pandemic, sometimes called the “Spanish flu,” is still a mystery. Except that the virus did not originate in Spain, the exact origin of the virus strain that caused the 1918 flu pandemic remains in dispute. One hypothesis recently advanced is based upon epidemiological research that suggests the most likely site of origin was Haskell County, Kansas, an isolated and sparsely populated county in the southwest corner of the state, in January 1918. Some epidemiologists argue that competing hypotheses (that the pandemic originated in Asia, or that it began in British Army camps) are not as well supported as evidence that the flu might have spread between United States Army camps and might have been carried by American troops to Europe. The first known U.S. outbreak of epidemic influenza was identified in epidemiological studies and in lay accounts as having occurred at Camp Funston, now Fort Riley, in Kansas. However, a previously unknown epidemic of influenza occurred in Haskell County, Kansas, 300 mi (483 km) west of Funston.

In late January and early February of 1918, a local physician in the county faced an epidemic of influenza of extraordinary suddenness and lethality. Dozens of previously strong and healthy patients were struck down as suddenly “as if they had been shot.” They then progressed to pneumonia and began to die. The local epidemic raged and worsened for several weeks and then disappeared as suddenly as it had emerged. Although influenza was not a reportable disease, the physician warned national public health officials, and this warning was published by the U.S. Public Health Service in “Public Health Reports” the Service's progenitor report to Morbidity and Mortality Weekly Report (MMWR). This report was the only reference in that journal to influenza anywhere in the world during the first six months of 1918. It was the first recorded instance in history of an influenza outbreak so violent that a physician warned public health officials, suggesting a new virus was adapting to humans with lethal effect.

During the Haskell County outbreak, local Army personnel reported to Funston for training. Also, friends and family visited them at Funston and soldiers came home on leave and then returned to Funston. The local press recorded several cases between February 26 and March 2 of people from the county who had visited the army base who either fell ill themselves or who had children that were stricken with influenza and pneumonia. The first soldier at the camp reported ill with influenza at sick call on March 4. Within three weeks, more than 1,100 soldiers at the camp, which held an average of 56,222 troops, required hospitalization, and thousands more required infirmary treatment. Meanwhile, Funston sent an uninterrupted stream of men to other American locations and to Europe, especially France. On March 18, influenza cases were reported in Camps Forrest and Greenleaf in Georgia. By the end of April, 24 of the 36 main Army camps suffered an influenza epidemic. Thirty of the 50 largest cities in the country also had a spike in excess mortality from influenza and pneumonia in April.

Also at the end of April, influenza erupted in France, beginning at Brest, the main port of disembarkation for American troops. After that, army operations proved to be the most influential factor in the spread of the epidemic elsewhere in the world. It seems likely that military policymakers either did not appreciate the role of their operations in spreading the epidemic or chose to regard it as an unfortunate but necessary consequence of war. Another lesson from this occurrence has been that a worldwide flu epidemic could potentially emerge anywhere, including a sparsely populated county in the United States, not only in a densely populated region in Asia.

Typhus Fever in World War I

As devastating as the 1918 flu pandemic was for the military and civilian populations alike during the latter part of World War I, it probably did not influence the course of the war and of history as much as the outbreak of typhus fever on the European Eastern Front during the first World War. Typhus fever is a louse-borne disease, and the lice that carry typhus fever are common in large aggregations of persons who do not bathe or change clothes with any regularity and are forced by circumstances to live in close quarters, which are also the situations that infantry, refugees, and prisoners are likely to encounter. In late November of 1914, typhus fever, which had been endemic in Serbia for centuries, began to appear among Serbian refugees fleeing the Austrian attack on Belgrade. Shortly afterwards, cases were reported from the army and among the prisoners of war, but caused little alarm. However, this disease had played a decisive role earlier in European military history, when, in 1812, typhus fever shattered Napoleon's invasion of Russia, destroying the French army well before it reached Moscow.

WORDS TO KNOW

AEROSOL: Particles of liquid or solid dispersed as a suspension in gas.

BIOMODULATOR: A biomodulator, short for biologic response modulator, is an agent that modifies some characteristic of the immune system, which may help in the fight against infection.

DEBRIDEMENT: Debridement is the medical process of removing dead, damaged, or infected tissue from pressure ulcers, burns, and other wounds, in order to speed healing of the surrounding healthy tissue.

ENDEMIC: Present in a particular area or among a particular group of people.

ENTEROPATHOGEN: An enteropathogen is a virus or pathogen that invades the large or small intestine, causing disease.

EXOTOXIN: A toxic protein produced during bacterial growth and metabolism and released into the environment.

MATERIEL: A French-derived word for equipment, supplies, or hardware.

PROPHYLAXIS: Treatment to prevent the onset or recurrence of disease.

PYROGENIC: A substance that causes fever is pyrogenic. The word “pyrogenic” comes from the Greek word pyr meaning fire.

The Austrian invasion was soon repulsed, but the devastation of Northern Serbia created ripe conditions for the spread of typhus. The first outbreak of cases occurred among Austrian prisoners at Valjevo, followed within a week by outbreaks throughout the rest of the country. The infection traveled with the refugee population, on prisoner of war trains, and with moving armies, and was rapidly disseminated to all parts of Serbia, resulting in a scene of horror reminiscent of the Black Death. At the start of World War I, Serbia numbered some three million people. Within six months, one in six Serbians developed typhus fever. Over 200,000 people, including 70,000 Serbian troops and half of the 60,000 Austrian prisoners, died from the disease. The outbreak spread beyond Serbia into Russia, as the famine and dislocation of the Russian revolution destroyed sanitation and social infrastructure, eventually resulting in 20 million cases in that country, half of whom died.

War and Forced Migration

A study carried out between January and March 2004, with Liberian refugee women staying at the United Nations refugee camp at a village in Nigeria, shows how forced migration contributes to increased incidence of communicable diseases. Liberia's civil war resulted in approximately 215,000 refugees at the end of 2001. During the civil war, according to some estimates, up to 40% of all Liberian women were raped. Loss of family exposed women to increased rape, prostitution, and increasing risk of HIV and other sexually transmitted infections. Lack of postwar shelter compounds other problems and increased exposure to mosquito-borne diseases. Lack of clean drinking water introduced risks of bacillary dysentery, cholera, diarrheal disease, typhoid, hepatitis A, and other diseases.

Recent War Experience: Operation Iraqi Freedom

In the spring of 2003, 83,000 United States Marines participated in the opening phase of Operation Iraqi Freedom. A Navy Preventive Medicine Department laboratory was set up to provide diagnostic support for Marine medical units during a period of repositioning in south-central Iraq. Specimen collection boxes were sent to more than 30 primary-care medical stations handling 500-900 personnel each. The laboratory had the capability to detect many different disease agents. By far the most common reason for infectious disease sick call visits was gastrointestinal illness; no other symptoms had equivalent impact. An enteropathogen was detected in 23% of stool samples, with norovirus detected in 30 stool samples obtained from 14 different battalion or similarsized units; next in frequency were Shigella flexneri and Shigella sonnei, which were isolated from 26 stool samples (20%) obtained from 15 units. Ciprofloxacin was effective in vitro against most bacterial agents, but neither doxycyline (which was taken daily as the antimalarial prophylaxis dose) nor trimethoprim-sulfamethoxazole were effective. Otherwise, personnel remained free of infectious illness during this phase of the conflict, because other infectious agents were rare or absent.

War Wounds

Nothing is more basic to a discussion of war and infectious disease than the control of wound infections. Prior to contemporary efficient and airborne medevac procedures, military surgeons worked by a rule of thumb: patch up and move on. Even today, at frontline dressing stations no time is wasted on the hopelessly injured. A seriously wounded soldier has to survive the stretcher trip through the field treatment station, hospital station, evacuation hospital to base hospital, sometimes in a different country, before he or she receives the medical luxuries of thorough surgical care, as when American combatants in contemporary Iraq are given definitive treatment in a hospital in Germany. It is a given in the military that “every wound is infected.” For example, prior to World War I, tetanus, a great killer in all previous wars, was practically eliminated by routine injections of anti-tetanic serum to all wounded soldiers.

Penicillin was first tested for military use in the spring of 1943. By autumn, doctors were using the antibiotic in combat zones, where it was limited to American and Allied military and to patients with life threatening infections. Flight crews of the Eighth Air Force stationed in Britain were the first to directly benefit from the drug. Rationing was necessary, as a single infection could require two million or more units of the drug. During the war, the armed forces received 85% of the nation's production. With the implementation of successful mass-production techniques, production of units tripled during 1944–1945. Penicillin became the war's wonder drug, and its remarkable medical effects on infectious disease made World War II different from any previous war.

The mass production of penicillin for military use gave impetus to the widespread use of antibiotics to fight infection on a wide scale in civil society after the war. Contemporary antibiotic-resistant bacterial strains pose an analogous threat to wounded troops. In spite of anti-biotic treatment and better antiseptic practices under combat conditions, it is still necessary to debride wounds and amputate seriously damaged limbs under combat situations in order to prevent gangrene and other runaway infection. The first use of debridement, the surgical excision of necrotic (dead) or infected tissue and the removal of foreign bodies from contaminated wounds to forestall infection, was made by a French medical officer in 1914. Prior to the introduction of debridement, all but simple incised wounds were treated by surgically opening the wound, removing obvious foreign bodies, and then irrigating with sterile salt solution or oxidizers such as hydrogen peroxide in an attempt to sterilize the lesion. The wound was left open and freely drained or was packed with gauze, and immobilized by suitable splints if necessary. Discharge of pus was treated by drainage tubes made of glass or rubber.

War and Public Health Infrastructure Damage

Often the public health impact of war goes unmeasured, but efforts were made to gauge the effects of the Balkan wars in the early 1990s. A public health assessment in Bosnia-Herzegovina and in the areas of Serbia and Montenegro hosting Bosnian refugees in 1993 revealed widespread disruption to basic health services, displacement of more than one million Bosnians, severe food shortages in Muslim enclaves, and extensive destruction of public water and sanitation systems. War-related violence was the most important public health risk in that nation. Civilians on all sides of the conflict were intentional targets of physical and sexual violence. The impact of the war on the health status of the population was difficult to document; however, in central Bosnia, perinatal and child mortality rates doubled between 1991 and 1993. The crude death rate in one Muslim enclave between April 1992 and March 1993 was four times the pre-war rate. Prevalence rates of severe malnutrition among both adults and children in central Bosnia increased steadily throughout the course of the conflict. Major epidemics of communicable diseases were not reported, however, but public health conditions were ripe for such epidemics. The lack of epidemics in this case is scientifically significant to infectious disease studies. It challenges many historical assertions and assumptions about public health in war time.

Impacts and Issues

The intentional release of biological agents by belligerents or terrorists is a possibility that has received urgent attention following the anthrax attacks in the United States in 2001, but which was under intensive study by the military prior to that time. Law enforcement agencies, military planners, public health officials, and clinicians are gaining an increasing awareness of this potential threat. From a military perspective, an important component of the protective pre-exposure resources against this threat is immunization. In addition, certain vaccines are an accepted component of post-exposure prophylaxis against potential bioterrorist threat agents. These vaccines might, therefore, be used to respond to a terrorist attack against civilians.

Biological warfare agents may be classified in several ways: (1) operationally, as lethal or incapacitating agents, and as agents with or without potential for secondary transmission; (2) according to intended target, as anti-personnel, antianimal, antiplant, or antimateriel; and (3) according to type, as replicating pathogens, toxins, or biomodulators. Among the greatest threats are both replicating pathogens (bacteria and viruses) and toxins.

Anthrax: Fortunately, few infectious agents possess characteristics suitable for effective large-scale employment. However, Bacillus anthracis has properties that are ideal for this purpose. It is omnipresent in soil and the ease with which it can be cultured makes anthrax readily available to armies and to terrorists. Its lethality, ability to form tough spores, and its affinity for aerosolization (production as a fine mist) combine to make anthrax one of the greatest biological threats. Anthrax was prominent in the biological weapons programs of Iraq and the former Soviet Union; the Aum Shinrikyo cult also stockpiled it. The World Health Organization (WHO) estimates that the release of 110 lb. (50 kg) of anthrax spores along a 1.2-mi (2-km) line upwind of a city of 500,000 people would produce 125,000 infections and 95,000 deaths, far more than with any other agent considered. Consequently, research programs at military laboratories have devoted considerable effort to improving on the anthrax vaccines that have been in use for decades.

Plague: One of the earliest recorded attempts at biological warfare was the effort of besieging Tatar warriors to catapult the corpses of their own plague victims over the city walls of Kaffa in the Crimea in order to initiate an epidemic within the city. The Japanese released millions of infected fleas over Manchurian cities, resulting in numerous human plague cases. During the Vietnam War, plague vaccine was routinely administered to members of the United States armed services, and only eight cases of plague were reported among this population, which corresponds to a rate of about one case per million person-years of exposure. The success of this vaccine is evident when compared with the 330-fold greater incidence of plague among the unvaccinated South Vietnamese civilian population.

Brucellosis: Brucellosis is considered to be an incapacitating agent likely to produce large numbers of casualties but little mortality. Nevertheless, brucellosis is highly infective. In the 1950s the United States chose Brucella suis as the first agent to be produced for its biological warfare program. Veterinary vaccines that have significant efficacy against brucellosis have been studied and employed. The vaccination of livestock in combination with the slaughter of infected animals is largely responsible for the declining incidence of human brucellosis. In the United States, the decline of human brucellosis cases reported to the CDC has paralleled the control of infections due to Brucella abortus in cattle.

Tularemia: Francisella tularensis is sometimes considered a lethal biological warfare agent, since high-dose aerosol dissemination would result in a disproportionate number of cases of the pneumonic form of tularemia. F. tularensis followed B. suis into the United States bioweapons program in 1955, and extensive testing of the weaponization potential of the agent was conducted in human volunteers at Fort Detrick. The organism was also thought to have been prominent in the biological arsenal of the Soviet Union. American and Russian collaboration has provided the seed stock for tularemia vaccines currently in use throughout the world.

Q fever: Coxiella burnetii, the causative agent of Q fever, is a gram-negative coccobacillus resistant to heat and dryness that grows easily in embryonated chicken eggs and is highly infectious by aerosol. This organism was cultivated by the United States bioweapons program as a potential incapacitating agent.

Smallpox: Although endemic smallpox was eradicated throughout the world in 1977, the virus remains a potential biological weapon in the eyes of many military planners. Concerns persist that clandestine stocks of virus may exist outside of CDC in Atlanta, Georgia, and Koltsovo in Russia, the two WHO-authorized repositories of the virus.

Botulism: Iraq chose to weaponize botulinum toxin during the Gulf War in 1991, although its usefulness as a weapon might be limited by its instability during storage and modest range upon aerosolization. Nonetheless, when delivered by aerosolization, botulinum toxins would be expected to produce cases of typical clinical botulism. Moreover, terrorists might also use botulinum toxins to sabotage food supplies. No licensed vaccine exists today.

Staphylococcal enterotoxin B (SEB) intoxication: SEB is one of several pyrogenic exotoxins produced by Staphylococcus aureus, and is considered a viable incapacitating agent by biological warfare planners. Although SEB is a cause of food-borne disease, its use in biological warfare would likely involve aerosolization, with which it would cause a systemic fever accompanied by pulmonary symptoms. No SEB vaccine is currently available for human use.

Although the United States Department of Defense has initiated an anthrax immunization campaign throughout the armed forces, it is likely that other anti-biological-warfare vaccines will eventually be employed to protect armed services personnel. In a civilian context, use of these vaccines is more problematic, because the nature of the threat is less well defined. Nonetheless, certain vaccines, such as anthrax and smallpox, may have applicability in the prevention and management of exposed civilian populations.

BIBLIOGRAPHY

Books

Barry, J.M. The Great Influenza: The Epic Story of the Deadliest Plague in History. New York: Viking, 2004.

Zinsser, Hans. Rats, Lice and History. Boston: Little, Brown & Company, 1935 (reprinted 1996).

Periodicals

Toole, M.J., S. Galson, and W. Brady. “Refugees, Forced Displacement, and War: Are War and Public Health Compatible?” The Lancet 341, 8854 (May 8, 1993): 1193–1196.

Web Sites

Jiang, X., et al. Cabi.org. “Gastroenteritis in U.S. Marines During Operation Iraqi Freedom.” <http://www.cababstractsplus.org/google/abstract.asp?AcNo=20053058791> (accessed June 1, 2007).

U.S. Army Center for Health Promotion and Disease Prevention. “Medical Threats Briefing Homepage.” <http://usachppm.apgea.army.mil/HIOMTB> (accessed June 1, 2007).

World Health Organization. “Global Atlas of Infectious Diseases.” <http://gamapserver.who.int/GlobalAtlas/home.asp> (accessed June 1, 2007).

Kenneth LaPensee

Infectious Diseases: In Context