assessment of human health risks from rodent-borne diseases by means of ecological studies of rodent reservoirs, The

Military Medicine, Jan 2002 by Zizi, Martin

Zoonoses in general, and more specifically rodent-borne diseases, have proven to be of increasing importance in recent decades. The study of vector biology, therefore, is the foundation for understanding the infection mechanisms for humans. Military operations on the European and Asian continent have been substantially affected by Hantavirus infections during World War I and World War II, the Korean War, and the more recent events in Bosnia. The recently discovered Hantavirus serotypes with high mortality may extend the risk for the future to North America. In this article, we focus on the host and ecosystem relationships that might be useful in predicting potential outbreaks in Western Europe.

Introduction

Emerging infectious diseases associated with small mammal reservoirs have increased dramatically in recent years, and reservoir ecology research has become an integrated part of the assessment of the potential risk for humans. The importance of understanding host and vector ecology has been recognized for bacterial, parasitic, and viral diseases.

Two distinct groups of negative-stranded RNA viruses, the arenaviruses (family Arenaviridae) and the hantaviruses (genus Hantavirus, family Bunyaviridae), cause severe emerging infectious diseases, such as the rodent-borne hemorrhagic fevers. Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) and Hantavirus pulmonary syndrome, whereas arenaviruses are responsible for Lassa fever in Africa, Argentinian (Junin virus), Bolivian (Machupo virus), and Venezuelan (Guanarito virus) hemorrhagic fever, and lymphocytic choriomeningitis infections worldwide. Each virus in these two groups is generally associated with a single species of rodent host of the family Muridae.

In Europe, arenaviruses pose no risk to public health, in contrast to hantaviruses. Each year, hantaviruses cause of thousands of cases of HFRS in Europe and tens of thousands of cases in Asia. Until recently, Hantavirus disease was apparently absent in the Americas, with the exception of rare cases of mild HFRS associated with Seoul (SEO) virus.' In 1993, however, the emergence of Hantaus pulmonary syndrome, with a mortality rate of approximately 50%, took virologists in the United States by surprise. Testing of patient sera against a vast panel of antigens revealed that the mysterious disease was caused by an unknown member of the Hantavirus genus. Vector studies revealed that the causative agent, Sin Nombre virus, was hosted by the deer mouse (Peromyscus maniculatus). Since then, at least 20 additional hantaviruses have been isolated from rodents throughout the Americas, and about 10 of them are human pathogens.2

The Military Relevance of Hantaviruses

Hantaviruses have had a considerable impact on military operations. During World War I, an epidemic struck French,3 British,4 and German soldiers, with the disease described as "nephrite de guerre," "trench nephritis," or "Kriegsnephritis." A report from 1916 presented the hypotheses that the agent was of viral origin and implicated the same agent responsible for the epidemic of renal disease observed during the American Civil War.5

During World War II in Finnish Lapland, 16,000 German troops were affected by a disease known to the local population as "Lemming fever," which showed a strong resemblance with Hantavirus infection.6

Modern Western medicine was first confronted with the severe Far Eastern form, Korean hemorrhagic fever (KHF), during the Korean War (1951-1953). U.S. Army physicians witnessed an outbreak of an unknown acute febrile illness with shock, acute renal failure, and hemorrhage; the disease affected more than 3,000 United Nations troops' and showed a mortality rate of 10 to 15%. The cause of the disease remained a mystery until 1976, when Lee and coworkers discovered the KHF virus-specific antigen in the lungs of a Korean striped field mouse (Apodemus agrarius Coreae); in 1977, the agent was isolated.' The prototype agent was called Hantaan after the river that divided North and South Korea along the 38th parallel. A collection of about 600 lyophilized sera from 245 soldiers admitted with KHF between December 1951 and August 1954 was preserved in the United States. Of these 254 patients, 94% (230 of 245) proved to be positive for Hantaan immunoglobulin M and/or immunoglobulin G antibodies.9

In Europe, the first epidemic after World War II took place in 1952 in Fruska Gora (Bosnia) during maneuvers of the Yugoslavian army. 10 The first isolation of a Hantavirus in Europe was made on the urine of a Greek soldier who was infected during maneuvers in northern Greece. 11

In January 1990, U.S. troops participating in the REFORGER exercise camped in the Ulm area of Germany. During the following 2 weeks, 16 military personnel suffered an acute Hantavirus infection that was later identified as being caused by Puumala virus. 12 During the armed conflict in Bosnia-Herzegovina in 1995, an important outbreak was reported. 13 More recently, a British soldier stationed in Bosnia (UNPROFOR) suffered from a severe Hantavirus infection and needed repatriation and intensive care treatment in the United Kingdom.14