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A study of nephropathia epidemica among military personnel in sweden
Res. Virol.
(~) INSTITUT PASTEUR/ELSEVIER Paris 1992
1992, 143, 211-214
A study of nephropathia epidemiea among military personnel in Sweden B. Niklasson (~, 2) (*), M. Jonsson (2), I. Widegren (~), K. Persson (3) (+) and J. LeDuc (4) to Swedish Defense Research Establishment, FOA-5, S-172.90 Sundbyberg (Sweden), (2) Department of Virology, National Bacteriological Laboratory, S-105.21 Stockholm, r3) MILO NN, Box 370, S-831.25 Ostersund (Sweden), and (4) Disease Assessment Division, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick 21702, MD (USA) SUMMARY The incidence of nephropathia epidemica (NE), caused by Puumala virus, among military troops operating in an endemic area of Sweden was investigated. A total of 705 soldiers (age 18-25) involved in field training in three different endemic counties were bled twice within a 6-month interval. Three individuals seroconverted when tested for Puumala virus antibodies by IgG ELISA. Symptoms typical of NE were not recorded in any of the patients. However, mild febrile episodes were recorded in 2 of the 3 individuals. One serologically confirmed soldier with typical NE symptoms was found in another group of 12,000 troops. This soldier fell ill 3 weeks after a 7-day-long field exercise. The present study indicates that military populations are at considerably greater risk of contracting NE when compared to the entire population residing in the same area.
Key-words: Puumula virus, Nephropathia epidemica, HFRS; Sweden, Soldiers.
INTRODUCTION
Between 1951 and 1954, more than 3,000 United Nations troops stationed in Korea developed a disease not previously recognized by western physicians. The illness, which was characterized by fever, headache, abdominal pain, renal dysfunction and various haemorrhagic manifestations, became known as Korean haemorrhagic fever. It soon became clear that clinically identical or closely related diseases occurred in large parts of Asia and Europe. The name haemorrhagic fever with renal syndrome
(HFRS) was suggested by Gajdusek and is now widely accepted (Gajdusek, 1962). Nephropathia epidemica (NE) caused by Puumala virus (PUU) is a milder form of HFRS occurring in Scandinavia and Finland (L~ihdevirta, 1971; Niklasson and LeDuc, 1987; Settergren et al., 1988). The incidence of serologically confirmed NE cases in Sweden has recently been documented (Niklasson and LeDuc, 1987; Settergren et al., 1988). The aim of the present study was to investigate the incidence of NE among military troops operating in an endemic area of Sweden.
Submitted January 15, 1992, accepted March 19, 1992. (+) Deceased. (*) Address reprint requests to Bo Niklasson, Department of Virology, National Bacteriological Laboratory, S-105.21 Stockholm, Sweden.
212
B. N I K L A S S O N E T A L . MATERIALS A N D M E T H O D S
Study populations O n e group of 558 soldiers (age 18-25) was stationed in V/irmland county, from November, 1984 to April, 1985 (fig. 1). During this period they were involved in a 3-week field exercise. A second group consisted of 147 soldiers (age 18-25) involved in continuous field training from September 1987 to February 1988 in two areas; 90 soldiers in V/isternorrland county and 57 soldiers in Jfimtland county (fig. 1). Serum specimens were collected from all 705 soldiers immediately before and after the study period. A third group consisted of approximately 12,000 soldiers (20-38 years of age) involved in a 7-day field exercise in V/isternorrland in October 1987. No sera were collected from this group; however, clinical surveillance was carried out by monitoring suspected cases.
The counties of Vfirmland, V/isternorrland and Jfimtland are in the endemic area of Sweden. Incidence rates were calculated for each county on the basis of population estimates as of December 31, 1987 (official statistics of Sweden, 1988).
V~sterbot~ ne~ ~
LAN~~~F~
R e p o r t e d clinical cases
In case of disease, all Swedish military personnel are first sent to the medical officer at the military base where their visits are documented. Patients requiring hospital care are routinely examined by the military medical officer and then referred to a civilian hospital if necessary. All laboratory confirmed NE cases in Sweden are reported to the epidemiological department of the National Bacteriological Laboratory (NBL), Stockholm, Sweden. NBL collects information on age, sex, date of onset and county of residence of all laboratory confirmed cases.
Serology
Serum specimens were tested for the presence of Puumala-specific IgG antibodies by ELISA as described elsewhere (Niklasson et al., 1991). In short, rabbit anti-PUU virus immunoglobulin was adsorbed to microtitre plates, followed by virus antigen, test serum and swine anti-human IgG conjugated with alkaline phosphatase. P-nitrophenol-phosphate (Sigma) was used as substrate. All specimens were tested in duplicate with antigen and negative control antigen. The OD was calculated as the average OD with antigen minus the average OD with negative control antigen. The border between positives and negatives was calculated as the mean of the test result of 142 known negative sera (from non-endemic areas and negative by IgG indirect immunofluorescence test) plus 3 standard deviations. An OD of > 0.080 was considered as positive.
V~STERNORRLAND
v~M
" ~ "~~r
.~
~")L~:~ ~
uMES
NORRLANDICUS
AREA
Fig. 1. The limes norrlandicus demarcate the southern distribution boundary of NE in Sweden. The study areas are Jfimtland, Vfisternorrland and Varmland Vfisterbotten county, the most endemic area in Sweden, is also shown.
HFRS NBL NE
= = =
haemorrhagic fever with renal syndrome. National Bacteriological Laboratory (Stockholm). nephropathia epidemica.
RESULTS Serological
results
A m o n g the 705 soldiers with both pre- and post-service serum specimens, PUU-specific antibodies were found in both pre- and post-service sera in 23 soldiers. Three individuals seroconvetted (table I). Medical records were available f r o m all 705 soldiers, but no individual was diagnosed with NE by military doctors during the period o f service. The military medical records showed that 2 o f the 3 soldiers who seroconverted suffered f r o m one or more febrile episodes.
OD
=
PUU
= Puumula(virus).
optical density.
213
NEPHROPA THIA EPIDEMICA IN SWEDISH TROOPS
Table I. Soldiers bled before and after serving in NE endemic counties of Sweden.
Endemic region
No. of soldiers
Antibody positive in pre-service sera
V~irmland V~isternorrland J~imtland
558 90 57
19 (3.4 %) 4 (4.4 %) 0
No. of seroconversions (per 100,000)
Annual incidence in civilian population
2 (358) 1 (1111) 0
3.2 13.8 6.4
The incidenceof infectionsper 100,000is calculatedbased on the rate of seroconversion.
These febrile events were described as mild, without any symptoms typical of NE such as high fever, severe general malaise and abdominal or low back pain. The third individual had no recorded febrile episode. All 12,000 soldiers participating in the 7-day long field exercise were compared to the NBL records of all laboratory confirmed NE cases during 1987. One serologically confirmed NE patient was found in this group. This individual had a clinically typical NE and fell ill 3 weeks following the field exercise.
DISCUSSION Historically, HFRS has been a disease of military significance. During the Korean conflict, several thousand UN troops fell ill in Korean haemorrhagic fever (Gajdusek, 1962). The first major outbreak of NE was reported during World War II, when numerous cases occurred a m o n g Finnish and German troops in the area of Salla in northern Finland (Stuhlfauth, 1943). Some investigators estimated this NE epidemic to have involved more than 10,000 cases (Jellison, 1971). In Sweden, a close association between NE and the natural vertebrate host, the bank vole (Clethrionomys glareolus), has been established. Populations of small mammals, including bank voles, fluctuate in the endemic region during a three- to four-year cycle of abundance and the n u m b e r of h u m a n cases coincides closely with these fluctuations (Nystr6m, 1977; Niklasson
and LeDuc, I987). These studies also revealed a seasonal pattern, with most cases occurring during the winter months and very few cases during April to July. The present study was performed during periods when the the bank vole was abundant in the areas investigated and at the time of the year when most cases would be expected. The rate of seroconversion among exposed military gives an infection rate of 358/100,000 soldiers in V~irmland, and 1 , I l l / 1 0 0 , 0 0 0 in V~isternorrland (table I). A previous study comparing antibody prevalence in the civilian population with the number of diagnosed cases suggested that the ratio of cases to infections in the male population was approximately 1/14 (Niklasson et al., 1987). The annual incidence rates of NE in the whole population of VArmland in 1984/1985 and of V~isternorrland and J/imtland in 1987/1988, were 3.2, 13.8 and 6.4 per 100,000 inhabitants, respectively. Based on these figures, the soldiers appear to have contracted the NE infection 6-8 times more often than the civilian population living in the same area. In addition, the exposure periods in the present study were shorter (in some instances, much shorter) than one full season. This fact would add to the estimated annual incidence a m o n g military personnel. An earlier study found V~isterbotten county to have the highest annual incidence in Sweden, with approximately 30 cases per 100,000 inhabitants. Extrapolation from the above figures, with the annual military incidence being 6-8 times higher than
214
B. N I K L A S S O N E T A L .
that of civilians, suggests that approximately 180-270 cases per 100,000 might be affected within the military population while serving in the field. One serologically confirmed patient was reported among the 12,000 soldiers exposed for one week. The annual incidence would be 217/100,000 assuming that NE is transmitted during 6 months of the year. Although the calculations made above are based on approximations and are not intended to be exact, the present study indicates the magnitude of the problem that NE may cause among troops stationed in endemic regions. Data from the military outbreak among German troops in Salla show that NE may have a very focal distribution (Stuhlfauth, 1943). Therefore military activities in the most endemic area risk occasional large outbreaks if entering a " h o t spot". It remains to be determined whether these " h o t spots" depend on certain ecological parameters, correlating with vole populations such as rodent habitats, environmental conditions or meterological conditions. If they can be identified, it may be possible to map and predict areas with high risk as compared to areas with lower risk.
Acknowledgements This project was supported by grant DAMD 17/89/Z9010 from the US Army Medical Research and Development Command.
Etude de la n6phropathie 6pid6mique chez les militaires en Suede L'incidence de la ~> (NE) due au virus Puumula a ~t~ &udi6e chez 705 soldats ~g6s de 18/l 25 ans, op&ant dans trois zones end~miques en Su6de (2 prises de sang h 6 mois d'intervalle). Trois s&oconversions IgG ELISA ont ~t6 not6es ainsi que des f~bricules dans 2 des 3 cas. Les symptfmes caract~ristiques de la NE n'ont 6t~ relev~s chez aucun des 705 sujets. Dans un autre
groupe militaire de 12.000 sujets, un cas s6ropositif avec un tableau typique de NE a 6t6 observ6 au cours de la 4 e semaine d'un exercice militaire dans la campagne. Cette 6tude montre que le risque de contracter la NE est beaucoup plus important chez les militaires que dans la population <~globale>> d'une zone end6mique donn6e. Mots-cl~s: Virus Puumula, N6phropathie 6pid& mique, H F R S ; Su6de, Militaires.
References Gajdusek, D.C. (1962), Virus hemorrhagic fevers. Special reference to hemorrhagic fever with renal syndrome (epidemic hemorrhagic fever). J. Pediatr., 60, 841-857. Jellison, W.L. (1971), Korean hemorrhagic fever and related diseases: a critical review and a hypothesis. Mountain Press Pubi. Co., Missoula, MT. Lhhdevirta, J. (1971), Nephropathia epidemica in Finland. A clinical, histological and epidemiologicai study. Thesis. Ann. Clin. Res., 3 (suppl.), 8. Niklasson, B. & LeDuc, J. (1987), Epidemiology of nephropathia epidemica in Sweden. J. infect. Dis., 155, 269-276. Niklasson, B., LeDuc, J., Nystr6m, K. & Nyman, L. (1987), Nephropathia epidemica; incidence of clinical cases and antibody prevalence in an endemic area of Sweden. EpidemioL infect., 99, 559-562. Niklasson, B., Tkachenko, E., Ivanov, A.P., Van der Groen, G., Wiger, D., Andersen, H.K., LeDuc, J., Kjelsson, T. & Nystr6m, K. (1991), Haemorrhagic fever with renal syndrome" evaluation of ELISA for detection of Puumala-virus-specific lgG and IgM. Res. ViroL, 141, 637-648. Nystr6m, K. (1977), Incidence and prevalence of endemic benign (epidemic) nephropathy in AC county, Sweden, in relation to population density and prevalence of small rodents. Acta Med. Scand., 609 (suppl.), 1-92. Official Statistics of Sweden. Population. Dec 31 1987: part 3 Stockholm (1988): Statistics Sweden, S-102 50 Stockholm, Sweden. Settergren, B., Juto, P., Vadell, G., Trollfors, B. & Norrby, S.R. (1988), Incidence and geographic distribution of serologically verified cases of nephropathia epidemica in Sweden. Amer. J. Epidemiol., 127, 801-807. Stuhlfauth, K. (1943), Nachtrag zu dem "Bericht uber ein neues schlammfieberahnliches Krankheitsbild bei Deutchen Truppen in Lappland". Dtsch. reed. Wschr., 69, 439-443.
(~) INSTITUT PASTEUR/ELSEVIER Paris 1992
1992, 143, 211-214
A study of nephropathia epidemiea among military personnel in Sweden B. Niklasson (~, 2) (*), M. Jonsson (2), I. Widegren (~), K. Persson (3) (+) and J. LeDuc (4) to Swedish Defense Research Establishment, FOA-5, S-172.90 Sundbyberg (Sweden), (2) Department of Virology, National Bacteriological Laboratory, S-105.21 Stockholm, r3) MILO NN, Box 370, S-831.25 Ostersund (Sweden), and (4) Disease Assessment Division, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick 21702, MD (USA) SUMMARY The incidence of nephropathia epidemica (NE), caused by Puumala virus, among military troops operating in an endemic area of Sweden was investigated. A total of 705 soldiers (age 18-25) involved in field training in three different endemic counties were bled twice within a 6-month interval. Three individuals seroconverted when tested for Puumala virus antibodies by IgG ELISA. Symptoms typical of NE were not recorded in any of the patients. However, mild febrile episodes were recorded in 2 of the 3 individuals. One serologically confirmed soldier with typical NE symptoms was found in another group of 12,000 troops. This soldier fell ill 3 weeks after a 7-day-long field exercise. The present study indicates that military populations are at considerably greater risk of contracting NE when compared to the entire population residing in the same area.
Key-words: Puumula virus, Nephropathia epidemica, HFRS; Sweden, Soldiers.
INTRODUCTION
Between 1951 and 1954, more than 3,000 United Nations troops stationed in Korea developed a disease not previously recognized by western physicians. The illness, which was characterized by fever, headache, abdominal pain, renal dysfunction and various haemorrhagic manifestations, became known as Korean haemorrhagic fever. It soon became clear that clinically identical or closely related diseases occurred in large parts of Asia and Europe. The name haemorrhagic fever with renal syndrome
(HFRS) was suggested by Gajdusek and is now widely accepted (Gajdusek, 1962). Nephropathia epidemica (NE) caused by Puumala virus (PUU) is a milder form of HFRS occurring in Scandinavia and Finland (L~ihdevirta, 1971; Niklasson and LeDuc, 1987; Settergren et al., 1988). The incidence of serologically confirmed NE cases in Sweden has recently been documented (Niklasson and LeDuc, 1987; Settergren et al., 1988). The aim of the present study was to investigate the incidence of NE among military troops operating in an endemic area of Sweden.
Submitted January 15, 1992, accepted March 19, 1992. (+) Deceased. (*) Address reprint requests to Bo Niklasson, Department of Virology, National Bacteriological Laboratory, S-105.21 Stockholm, Sweden.
212
B. N I K L A S S O N E T A L . MATERIALS A N D M E T H O D S
Study populations O n e group of 558 soldiers (age 18-25) was stationed in V/irmland county, from November, 1984 to April, 1985 (fig. 1). During this period they were involved in a 3-week field exercise. A second group consisted of 147 soldiers (age 18-25) involved in continuous field training from September 1987 to February 1988 in two areas; 90 soldiers in V/isternorrland county and 57 soldiers in Jfimtland county (fig. 1). Serum specimens were collected from all 705 soldiers immediately before and after the study period. A third group consisted of approximately 12,000 soldiers (20-38 years of age) involved in a 7-day field exercise in V/isternorrland in October 1987. No sera were collected from this group; however, clinical surveillance was carried out by monitoring suspected cases.
The counties of Vfirmland, V/isternorrland and Jfimtland are in the endemic area of Sweden. Incidence rates were calculated for each county on the basis of population estimates as of December 31, 1987 (official statistics of Sweden, 1988).
V~sterbot~ ne~ ~
LAN~~~F~
R e p o r t e d clinical cases
In case of disease, all Swedish military personnel are first sent to the medical officer at the military base where their visits are documented. Patients requiring hospital care are routinely examined by the military medical officer and then referred to a civilian hospital if necessary. All laboratory confirmed NE cases in Sweden are reported to the epidemiological department of the National Bacteriological Laboratory (NBL), Stockholm, Sweden. NBL collects information on age, sex, date of onset and county of residence of all laboratory confirmed cases.
Serology
Serum specimens were tested for the presence of Puumala-specific IgG antibodies by ELISA as described elsewhere (Niklasson et al., 1991). In short, rabbit anti-PUU virus immunoglobulin was adsorbed to microtitre plates, followed by virus antigen, test serum and swine anti-human IgG conjugated with alkaline phosphatase. P-nitrophenol-phosphate (Sigma) was used as substrate. All specimens were tested in duplicate with antigen and negative control antigen. The OD was calculated as the average OD with antigen minus the average OD with negative control antigen. The border between positives and negatives was calculated as the mean of the test result of 142 known negative sera (from non-endemic areas and negative by IgG indirect immunofluorescence test) plus 3 standard deviations. An OD of > 0.080 was considered as positive.
V~STERNORRLAND
v~M
" ~ "~~r
.~
~")L~:~ ~
uMES
NORRLANDICUS
AREA
Fig. 1. The limes norrlandicus demarcate the southern distribution boundary of NE in Sweden. The study areas are Jfimtland, Vfisternorrland and Varmland Vfisterbotten county, the most endemic area in Sweden, is also shown.
HFRS NBL NE
= = =
haemorrhagic fever with renal syndrome. National Bacteriological Laboratory (Stockholm). nephropathia epidemica.
RESULTS Serological
results
A m o n g the 705 soldiers with both pre- and post-service serum specimens, PUU-specific antibodies were found in both pre- and post-service sera in 23 soldiers. Three individuals seroconvetted (table I). Medical records were available f r o m all 705 soldiers, but no individual was diagnosed with NE by military doctors during the period o f service. The military medical records showed that 2 o f the 3 soldiers who seroconverted suffered f r o m one or more febrile episodes.
OD
=
PUU
= Puumula(virus).
optical density.
213
NEPHROPA THIA EPIDEMICA IN SWEDISH TROOPS
Table I. Soldiers bled before and after serving in NE endemic counties of Sweden.
Endemic region
No. of soldiers
Antibody positive in pre-service sera
V~irmland V~isternorrland J~imtland
558 90 57
19 (3.4 %) 4 (4.4 %) 0
No. of seroconversions (per 100,000)
Annual incidence in civilian population
2 (358) 1 (1111) 0
3.2 13.8 6.4
The incidenceof infectionsper 100,000is calculatedbased on the rate of seroconversion.
These febrile events were described as mild, without any symptoms typical of NE such as high fever, severe general malaise and abdominal or low back pain. The third individual had no recorded febrile episode. All 12,000 soldiers participating in the 7-day long field exercise were compared to the NBL records of all laboratory confirmed NE cases during 1987. One serologically confirmed NE patient was found in this group. This individual had a clinically typical NE and fell ill 3 weeks following the field exercise.
DISCUSSION Historically, HFRS has been a disease of military significance. During the Korean conflict, several thousand UN troops fell ill in Korean haemorrhagic fever (Gajdusek, 1962). The first major outbreak of NE was reported during World War II, when numerous cases occurred a m o n g Finnish and German troops in the area of Salla in northern Finland (Stuhlfauth, 1943). Some investigators estimated this NE epidemic to have involved more than 10,000 cases (Jellison, 1971). In Sweden, a close association between NE and the natural vertebrate host, the bank vole (Clethrionomys glareolus), has been established. Populations of small mammals, including bank voles, fluctuate in the endemic region during a three- to four-year cycle of abundance and the n u m b e r of h u m a n cases coincides closely with these fluctuations (Nystr6m, 1977; Niklasson
and LeDuc, I987). These studies also revealed a seasonal pattern, with most cases occurring during the winter months and very few cases during April to July. The present study was performed during periods when the the bank vole was abundant in the areas investigated and at the time of the year when most cases would be expected. The rate of seroconversion among exposed military gives an infection rate of 358/100,000 soldiers in V~irmland, and 1 , I l l / 1 0 0 , 0 0 0 in V~isternorrland (table I). A previous study comparing antibody prevalence in the civilian population with the number of diagnosed cases suggested that the ratio of cases to infections in the male population was approximately 1/14 (Niklasson et al., 1987). The annual incidence rates of NE in the whole population of VArmland in 1984/1985 and of V~isternorrland and J/imtland in 1987/1988, were 3.2, 13.8 and 6.4 per 100,000 inhabitants, respectively. Based on these figures, the soldiers appear to have contracted the NE infection 6-8 times more often than the civilian population living in the same area. In addition, the exposure periods in the present study were shorter (in some instances, much shorter) than one full season. This fact would add to the estimated annual incidence a m o n g military personnel. An earlier study found V~isterbotten county to have the highest annual incidence in Sweden, with approximately 30 cases per 100,000 inhabitants. Extrapolation from the above figures, with the annual military incidence being 6-8 times higher than
214
B. N I K L A S S O N E T A L .
that of civilians, suggests that approximately 180-270 cases per 100,000 might be affected within the military population while serving in the field. One serologically confirmed patient was reported among the 12,000 soldiers exposed for one week. The annual incidence would be 217/100,000 assuming that NE is transmitted during 6 months of the year. Although the calculations made above are based on approximations and are not intended to be exact, the present study indicates the magnitude of the problem that NE may cause among troops stationed in endemic regions. Data from the military outbreak among German troops in Salla show that NE may have a very focal distribution (Stuhlfauth, 1943). Therefore military activities in the most endemic area risk occasional large outbreaks if entering a " h o t spot". It remains to be determined whether these " h o t spots" depend on certain ecological parameters, correlating with vole populations such as rodent habitats, environmental conditions or meterological conditions. If they can be identified, it may be possible to map and predict areas with high risk as compared to areas with lower risk.
Acknowledgements This project was supported by grant DAMD 17/89/Z9010 from the US Army Medical Research and Development Command.
Etude de la n6phropathie 6pid6mique chez les militaires en Suede L'incidence de la ~
groupe militaire de 12.000 sujets, un cas s6ropositif avec un tableau typique de NE a 6t6 observ6 au cours de la 4 e semaine d'un exercice militaire dans la campagne. Cette 6tude montre que le risque de contracter la NE est beaucoup plus important chez les militaires que dans la population <~globale>> d'une zone end6mique donn6e. Mots-cl~s: Virus Puumula, N6phropathie 6pid& mique, H F R S ; Su6de, Militaires.
References Gajdusek, D.C. (1962), Virus hemorrhagic fevers. Special reference to hemorrhagic fever with renal syndrome (epidemic hemorrhagic fever). J. Pediatr., 60, 841-857. Jellison, W.L. (1971), Korean hemorrhagic fever and related diseases: a critical review and a hypothesis. Mountain Press Pubi. Co., Missoula, MT. Lhhdevirta, J. (1971), Nephropathia epidemica in Finland. A clinical, histological and epidemiologicai study. Thesis. Ann. Clin. Res., 3 (suppl.), 8. Niklasson, B. & LeDuc, J. (1987), Epidemiology of nephropathia epidemica in Sweden. J. infect. Dis., 155, 269-276. Niklasson, B., LeDuc, J., Nystr6m, K. & Nyman, L. (1987), Nephropathia epidemica; incidence of clinical cases and antibody prevalence in an endemic area of Sweden. EpidemioL infect., 99, 559-562. Niklasson, B., Tkachenko, E., Ivanov, A.P., Van der Groen, G., Wiger, D., Andersen, H.K., LeDuc, J., Kjelsson, T. & Nystr6m, K. (1991), Haemorrhagic fever with renal syndrome" evaluation of ELISA for detection of Puumala-virus-specific lgG and IgM. Res. ViroL, 141, 637-648. Nystr6m, K. (1977), Incidence and prevalence of endemic benign (epidemic) nephropathy in AC county, Sweden, in relation to population density and prevalence of small rodents. Acta Med. Scand., 609 (suppl.), 1-92. Official Statistics of Sweden. Population. Dec 31 1987: part 3 Stockholm (1988): Statistics Sweden, S-102 50 Stockholm, Sweden. Settergren, B., Juto, P., Vadell, G., Trollfors, B. & Norrby, S.R. (1988), Incidence and geographic distribution of serologically verified cases of nephropathia epidemica in Sweden. Amer. J. Epidemiol., 127, 801-807. Stuhlfauth, K. (1943), Nachtrag zu dem "Bericht uber ein neues schlammfieberahnliches Krankheitsbild bei Deutchen Truppen in Lappland". Dtsch. reed. Wschr., 69, 439-443.