Becoming an International Scientist in South Korea: Ho Wang Lee's Research Activity about Epidemic Hemorrhagic Fever.

In the 1960-70s, South Korea was still in the position of a science latecomer. Although the scientific research environment in South Korea at that time was insufficient, there was a scientist who achieved outcomes that could be recognized internationally while acting in South Korea. He was Ho Wang Lee(1928~ ) who found Hantann Virus that causes epidemic hemorrhagic fever for the first time in the world. It became a clue to identify causative viruses of hemorrhagic diseases that were scattered here and there throughout the world. In addition, these outcomes put Ho Wang Lee on the global center of research into epidemic hemorrhagic fever. This paper examines how a Korean scientist who was in the periphery of virology could go into the central area of virology. Also this article shows the process through which the virus found by Ho Wang Lee was registered with the international academia and he proceeded with follow-up research based on this progress to reach the level at which he generalized epidemic hemorrhagic fever related studies throughout the world. While he was conducting the studies, experimental methods that he had never experienced encountered him as new difficulties. He tried to solve the new difficulties faced in his changed status through devices of cooperation and connection. Ho Wang Lee's growth as a researcher can be seen as well as a view of a researcher that grew from a regional level to an international level and could advance from the area of non-mainstream into the mainstream. This analytic tool is meaningful in that it can be another method of examining the growth process of scientists in South Korea or developing countries.

Hemorrhagic Fever with Renal Syndrome, Zibo City, China, 2006-2014.

Analysis of hemorrhagic fever with renal syndrome cases in Zibo City, China, during 2006-2014 showed that it occurred year-round. Peaks in spring and fall/winter were caused by Hantaan and Seoul viruses, respectively. Rodent hosts were the striped field mouse for Hantaan virus and the brown rat and house mouse for Seoul virus.

Hemorrhagic Fever with renal syndrome and its history in Iran.

Hemorrhagic fever with renal syndrome (HFRS) is a serious human disease of zoonotic viral origin. A group of different viruses that belong to the family of hemorrhagic fever could represent with HFRS. The basic pathophysiologic feature is virus-induced leaky microcirculation. There is no effective antiviral treatment against them. Because of rapid environmental changes, global warming, and increased global traveling, different hemorrhagic fever syndromes could be found anywhere in the world and beyond their old endemic borders. This review is a brief overview of HFRS in Iran during the early and mid-twentieth century.

Wars, disasters and kidneys.

This paper summarizes the impact that wars had on the history of nephrology, both worldwide and in the Ghent Medical Faculty notably on the definition, research and clinical aspects of acute kidney injury. The paper briefly describes the role of 'trench nephritis' as observed both during World War I and II, supporting the hypothesis that many of the clinical cases could have been due to Hantavirus nephropathy. The lessons learned from the experience with crush syndrome first observed in World War II and subsequently investigated over many decades form the basis for the creation of the Renal Disaster Relief Task Force of the International Society of Nephrology. Over the last 15 years, this Task Force has successfully intervened both in the prevention and management of crush syndrome in numerous disaster situations like major earthquakes.

The epidemic characteristics and changing trend of hemorrhagic fever with renal syndrome in Hubei Province, China.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is caused by different hantaviruses within the Bunyaviridae family. HFRS is a fulminant, infectious disease that occurs worldwide and is endemic in all 31 provinces of China. Since the first HFRS case in Hubei Province was reported in 1957, the disease has spread across the province and Hubei has become one of the seriously affected areas in China with the greatest number of reported HFRS cases in the 1980's. However, the epidemic characteristics of HFRS in Hubei are still not entirely clear and long-term, systematic investigations of this epidemic area have been very limited. METHODS: The spatiotemporal distribution of HFRS was investigated using data spanning the years 1980 to 2009. The annual HFRS incidence, fatality rate and seasonal incidence between 1980 and 2009 were calculated and plotted. GIS-based spatial analyses were conducted to detect the spatial distribution and seasonal pattern of HFRS. A spatial statistical analysis, using Kulldorff's spatial scan statistic, was performed to identify clustering of HFRS. RESULTS: A total of 104,467 HFRS cases were reported in Hubei Province between 1980 and 2009. Incidence of and mortality due to HFRS declined after the outbreak in 1980s and HFRS cases have been sporadic in recent years. The locations and scale of disease clusters have changed during the three decades. The seasonal epidemic pattern of HFRS was characterized by the shift from the unimodal type (autumn/winter peak) to the bimodal type. CONCLUSIONS: Socioeconomic development has great influence on the transmission of hantaviruses to humans and new epidemic characteristics have emerged in Hubei Province. It is necessary to reinforce preventative measures against HFRS according to the newly-presented seasonal variation and to intensify these efforts especially in the urban areas of Hubei Province.

Discovery of hantaviruses and of the Hantavirus genus: personal and historical perspectives of the Presidents of the International Society of Hantaviruses.

We three authors, the two past presidents (HWL and AV) and the current president (CSS) of the International Society for Hantaviruses (ISH) have attended most of the nine International Conferences on HFRS, HPS and Hantaviruses (Table 1). These conferences have provided a forum for a synergistic group of clinicians, basic researchers, mammalogists, epidemiologists and ecologists to share their expertise and interests in all aspects of hantavirus research. Much of what is now hantavirus dogma was only conjecture when HWL organized the first conference in Seoul, Korea in 1989. Herein, we provide our reflections on key events in hantavirus research. As we come from distinct areas of the world and have had individual historical experiences, we certainly have our own geocentric opinions about the key events. Nevertheless, we agree that the discovery of hantaviruses has taken an interesting and unpredictable track to where we are today.

Hantavirus infections in Europe: from virus carriers to a major public-health problem.

In Europe, hantavirus disease or hemorrhagic fever with renal syndrome is an endemic zoonosis that affects tens of thousands of individuals each year. The causative agents are viruses of the genus Hantavirus, family Bunyaviridae, rodents and insectivores act as carriers. In all European countries there is a seroprevalence for hantaviruses in the general population but not all countries report cases. Here, we give an overview of the hantavirus situation in Europe.

[Hemorrhagic fever with renal syndrome in Bosnia and Herzegovina--history review till 1990]. / Hemoragijska vrucica s bubreznim sindromom u Bosni i Hercegovini--povijesni pregled do 1990. godine.

The first data on a disease that was clinically similar to hemorrhagic fever with renal syndrome (HFRS) in Bosnia and Herzegovina, date from 1952. Fifteen years later, an outbreak in the territory of Bosanska Krajina, turned to a great HFRS outbreak in the Sarajevo area. The outbreak was considered as the largest HFRS outbreak in Eastern Europe ever described. After that time, HFRS occurred mostly sporadically, or as small epidemics in 1970, 1975 and 1986. A new large epidemic was registered in 1989, again mostly affecting the population of the Sarajevo area. According to different data sources, 452 HFRS patients, 26 of them with lethal outcome, were recorded in Bosnia and Herzegovina. In addition, HFRS was recorded in 11 soldiers who were on military service in the territory of Bosnia and Herzegovina. According to the results of several field studies, it appears justifiable to assume that the true prevalence of the disease was higher than diagnosed and reported. The reason was probably our failure to recognize HFRS due to the variable clinical manifestation and significantly greater frequency of mild or atypical forms than of the typical form of the disease. This is supported by the fact that inapparent infections were proven in approximately 5% of the examined healthy persons living close to the focal areas. The disease and inapparent infection were mostly observed in the groups of active population. The infections were most common in rural regions among foresters and farmers. Appodemus flavicollis was the main reservoir of hantaviruses in Bosnia and Herzegovina till 1990, and transmission was mainly by aerosol in the conditions of fresh contamination of the environment with excretions and secretions of small mammals. The intensity of the epidemic process is directly correlated with the intensity of the epizootic process as well as with the extent of human population exposure.

When half of the population died: the epidemic of hemorrhagic fevers of 1576 in Mexico.

During the 16th century, Mexico suffered a demographic catastrophe with few parallels in world's history. In 1519, the year of the arrival of the Spaniards, the population in Mexico was estimated to be between 15 and 30 million inhabitants. Eighty-one years later, in 1600, only two million remained. Epidemics (smallpox, measles, mumps), together with war, and famine have been considered to be the main causes of this enormous population loss. However, re-evaluation of historical data suggests that approximately 60-70% of the death toll was caused by a series of epidemics of hemorrhagic fevers of unknown origin. In order to estimate the impact of the 1576 epidemic of hemorrhagic fevers on the population we analyzed the historical record and data from the 1570 and 1580 censuses of 157 districts. The results identified several remarkable aspects of this epidemic: First, overall, the population loss for these 157 districts was 51.36%. Second, there was a clear ethnic preference of the disease, the Spanish population was minimally affected whereas native population had high mortality rate. Third, the outbreak originated in the valleys of central Mexico whence it evolved as an expansive wave. Fourth, a positive correlation between altitude and mortality in central Mexico was found. Fifth, a specific climatic sequence of events was associated with the initiation and dissemination of the hemorrhagic fevers. Although the last epidemic of hemorrhagic fevers in Mexico ended in 1815, many questions remain to be answered. Perhaps the most relevant ones are whether there is a possible reemergence of the hemorrhagic fevers and how vulnerable we are to the disease.

[Hemorrhagic fever with renal syndrome: historical aspects].

A mysterious disease was first reported from Korea when it had been observed during late spring 1951 in UN Forces operating in the central area close to the 38th parallel. The disease showed distinctive features which included high fever, low blood pressure, hemorrhagic tendency and acute renal failure. Historically it was apparently a similar disease to a clinical entity designated as Epidemic hemorrhagic fever in Manchuria or Hemorrhagic nephrosonephritis in Far Eastern Russia. After Lee Ho-Wang succeeded in demonstrating Hantaan virus which caused hemorrhagic fever with renal syndrome (HFRS), many studies has revealed various biological and epidemiological aspects of the disease. But the origin of the disease in Korea still remains unknown. This article tests some hypotheses which explain the origin of the disease and reviews the relation between the Korean War and HFRS. It is concluded that the emerging of HFRS would be closely related with the establishment of the munitions supply network in early 1951 in Chinese troop.

Hemorrhagic Fever with Renal Syndrome: Historical Aspects / 의사학

A mysterious disease was first reported from Korea when it had been observed during late spring 1951 in UN Forces operating in the central area close to the 38th parallel. The disease showed distinctive features which included high fever, low blood pressure, hemorrhagic tendency and acute renal failure. Historically it was apparently a similar disease to a clinical entity designated as Epidemic hemorrhagic fever in Manchuria or Hemorrhagic nephrosonephritis in Far Eastern Russia. After Lee Ho-Wang succeeded in demonstrating Hantaan virus which caused hemorrhagic fever with renal syndrome (HFRS), many studies has revealed various biological and epidemiological aspects of the disease. But the origin of the disease in Korea still remains unknown. This article tests some hypotheses which explain the origin of the disease and reviews the relation between the Korean War and HFRS. It is concluded that the emerging of HFRS would be closely related with the establishment of the munitions supply network in early 1951 in Chinese troop.

[Hemorrhagic fever with renal syndrome in Croatia--historical review]. / Hemoragijska vrucica s bubreznim sindromom u Hrvatskoj--povijesni pregled.

Hemorrhagic fever with renal syndrome (HFRS) has been known from ancient times as a disease with many names, which raised great interest during the Korean war (1951-1954), occurring as a large epidemic (Korean hemorrhagic fever). Therefore, the subsequently discovered causative agent was named after the Hantaan River which runs along the 38th parallel and divides North Korea from South Korea. A similar disease was described in 1934 in Scandinavian countries (epidemic nephrosonephritis or nephropathy). During the Second World War, the disease was also registered as wartime nephritis in several European south-eastern countries. Since 1982, similar clinical manifestations of the disease, differently named in various parts of the world, have been assigned one unique name--hemorrhagic fever with renal syndrome, as recommended by the World Health Organization. In Croatia, the first patient with HFRS was diagnosed in 1952 and the paper describing the case was published in 1954 (Radosevic and Mohacek). Since then, the disease has been regularly occurring in our country, especially in sporadic form, with only two smaller epidemics recorded until 1995. The first epidemic with 14 forestry workers involved occurred in 1967 at the Plitvice Lakes, and the second with the same number of soldiers in 1989 around the Pieso-Airport near Zagreb. Simultaneously, in 1967 and 1989 two large-scale epidemics of HFRS occurred in Bosnia and Herzegovina with 144 cases each. Until the first large epidemic of HFRS in Croatia during the Croatian War in 1995, occurring at several localities (Mala Kapela, Dinara mountain, west Slavonia), it was considered that there were only several natural foci of the disease in Croatia (around Ogulin and Slunj, Plitvice Lakes, Zagreb surroundings). A total of 125 cases were reported to the Croatian National Institute of Public Health in 1995. Fifty patients, 45 of them soldiers, were hospitalized at Dr. Fran Mihaljevic University Hospital for infectious Diseases in Zagreb. In the same year, the largest epidemic also occurred in Bosnia and Herzegovina with more than 300 cases. During the almost 50-year experience in HFRS surveillance, we have noticed two different clinical manifestations of the disease. The milder type of illness without hemorrhage is more common than the severe type with hemorrhages and extensive renal insufficiency. After the virus discovery and introduction of serologic testing, two causative agents have been detected during the 1970s and 1980s--Vranica and Fojnica, that were later serotyped as Puumala and Dobrava viruses.

Muroid virus nephropathies and muroid viruses of the Hantaan virus group.

Hemorrhagic fever with renal syndrome (HFRS) came dramatically to the attention of Western medicine in 1951 with the "new" disease becoming a major source of morbidity and mortality in American troops in Korea. Known there as epidemic hemorrhagic fever (EHF) or Korean hemorrhagic fever (KHF), it became apparent that it was the same disease as the endemic (epidemic) hemorrhagic nephroso-nephritis of the Soviet Far East and Songo fever of the Japanese Army in Manchuria. The conjecture that the milder epidemic (endemic) nephropathy of Scandinavia and European Russia was the same or a related disease has now been substantiated with the demonstration of close serological relationship of the Bunyamwera-like virus causing KHF (Hantaan virus) to that of HFRS in Finland, Sweden, European Russia, Greece and Yugoslavia. In the past decade the disease has been recognized as a serious problem in 19 provinces of China and in Japan, where the virus is the Hantaan virus. The severe EHF (or KHF) has its silent reservoir in the wild mouse Apodemus agrarius or in laboratory rats while the less virulent European disease resides in the voles Clethrionomys sp. A mild nonhemorrhagic form of the East Asian nephropathy is carried to man by infected urban rats, Rattus rattus or Rattus norvegicus, in Japan and Korea. All forms are carried to man as a respiratory infection "when a mouse (or rat or vole) coughs". Antibodies to the Hantaan virus have been found in man in India, Iran, Central Africa, Alaska, Bolivia and in wild rodents and urban rats in the USA where human cases of muroid virus nephropathy have not been recognized. Antibody patterns to Hantaan virus and to Scandinavian nephropathia epidemica virus antigens found in human and rodent sera in America and in Sweden, Yugoslavia, and European Russia suggest the possibility of yet a third (or more) virus serotype(s), and also the possible presence of the East Asian type of virus in Europe.