in early january 2005 , the french yersinia national reference laboratory ( ynrl ) received 3 y. pseudotuberculosis strains isolated by the same laboratory in dijon over a 1-week period : 2 from fecal samples of 2 children attending the same daycare center and 1 from the blood of a 65-year - old woman . during the same month , 8 additional strains were isolated from persons in other parts of the country by the yersinia surveillance network ( based on voluntary participation of 88 hospital - based and private - sector medical laboratories throughout france ) . in view of this unusually high number of y. pseudotuberculosis isolations over a short period ,
the ynrl alerted france s national disease surveillance network , the institut de veille sanitaire , which thereafter performed an epidemiologic investigation .
in early february , a request was mailed to all member laboratories in the yersinia surveillance network and all 95 microbiology laboratories in university medical centers , asking them to report any recent cases of y. pseudotuberculosis infection .
a reminder letter was mailed to all laboratories that had not replied within 1 month of the initial communication . moreover , from february through april 2005 , a total of 76 general medical center laboratories were contacted by telephone and asked to provide the ynrl with any relevant information and/or isolates .
overall , 27 cases of culture - confirmed y. pseudotuberculosis infections were spontaneously reported or actively retrieved ( table 1 ) . *
this patient s signs / symptoms began after hospitalization ; all other patients signs / symptoms began before hospitalization .
case reports of y. pseudotuberculosis infection peaked in january 2005 . a food - exposure analysis for the first 10 patients did not identify a potential common food source , so a food survey was not performed for subsequent cases .
the pseudotuberculosis cases occurred in 19 different counties throughout france , not necessarily the most populated ones ( figure 1 ) .
data on lifestyle and living conditions were obtained for all but 7 patients , of whom 3 had died and 4 ( including 2 children ) were lost to follow - up . of the 22 adults , 13 lived in small towns ( < 5,000 inhabitants ) and 5 lived in rural villages ( < 500 inhabitants ) .
of the 17 adults whose lifestyle was investigated in detail , 14 had a dog , hunted , gardened , and/or grew their own vegetables .
in contrast , all 5 children lived in urban areas ( > 50,000 inhabitants ) , compared with only 3 of the 22 adults ; 4 of the children lived in apartments .
map of france , showing spatial distribution of yersinia pseudotuberculosis infections during the winter of 200405 .
black circles , patients ' residences ; open circles , cities with medical laboratories that stated that they had not isolated any y. pseudotuberculosis from clinical specimens . of the 27 strains isolated , 25
all but 4 strains belonged to serotype i , the most common serotype in france .
pulsed - field gel electrophoresis after spei digestion of genomic dna showed that ( with the exception of the isolates from the 2 children attending the same daycare center ) the dna fingerprints of the 16 other isolates sent to the ynrl during the peak period were all distinct , even when the strains were isolated from the same county ( data not shown ) .
this episode of increased case numbers differs from episodes reported in the literature by the nationwide distribution of cases , the absence of a locally defined cluster , the genetic diversity of the isolates , the predominance of rural residence for patients , and the dominant clinical presentation of septicemia ( 38 ) . because the cases were not related to the consumption of a food product sold nationally ( e.g. , by a supermarket chain )
, the unknown origin of this phenomenon raises the question of an emerging risk in a new epidemiologic situation .
of the 27 patients , 19 lived in a strip of land that stretches from northern france to the atlantic coast and corresponds to the flyways of small migratory birds .
hence , the avian introduction of strains into the country would have been a possible scenario , as has already been suspected for an epizootic of pseudotuberculosis in an american wildlife park ( 9 ) . indeed , during the winter of 200405 , france witnessed a large and unexpected invasion of bohemian waxwings ( bombycilla garrulus ) ( 10 ) , a species known to migrate from circumpolar areas where pseudotuberculosis is endemic . at that same time , 3 pseudotuberculosis outbreaks were reported in siberia ( 11 ) . however , the genetic diversity of the strains isolated from the patients in france and the absence of pcr amplification of the superantigen - encoding gene ypm gene ( 12 ) ( which is highly prevalent in far eastern strains ) do not support bird - borne arrival in france of a y. pseudotuberculosis clone from russia or the far east .
these cases occurred in areas where other human cases of y. pseudotuberculosis septicemia had been diagnosed ( albeit at a much lower rate ) in the past 16 years ( figure 2 ) .
most previous cases of y. pseudotuberculosis septicemia also concerned inhabitants of low - altitude plains ( figure 2 ) , mainly in rural areas with extensive agriculture zones , which provide favorable habitats for small mammals .
cases were frequently ( 27.1% ) reported in 5 central - western counties of france , where just 4.6% of the population live and incidence of francisella tularensis infection ( tularemia ) is high ( 27.3% ) ( www.invs.sante.fr/surveillance/tularemie/donnees.htm ) .
moreover , 40 cases of tularemia ( with incidence peaks in summer and autumn ) were reported to the national surveillance system in 2004 ( notification of the disease has been obligatory since 2002 ) , whereas only 8 to 19 cases per year had been reported over the preceding and following periods . like y. pseudotuberculosis , f. tularensis is known to have a rodent reservoir .
hence , the spatial and temporal correlations between human tularemia and pseudotuberculosis in france over recent years suggest the sudden expansion of a common reservoir in 2004 .
county distribution , france , of yersinia pseudotuberculosis isolated from human blood and reported to the yersinia national reference laboratory over the 16 years preceding the winter of 200405 . the number of isolates is represented by proportionally sized circles arbitrarily located at the center of the counties .
our analysis of the temporal distribution of human y. pseudotuberculosis septicemia cases over the past 16 years showed a peak every 5 years ( table 2 ) .
this finding is reminiscent of human hantavirus infections , which have been linked to cyclical oscillations in the vole population ( the virus reservoir ) . taken as a whole , these data suggest that a rodent reservoir , mainly in rural areas , could have suddenly increased in the spring of 2004 , thus increasing the risk for human transmission of y. pseudotuberculosis and f. tularensis over the following months .
* received by the french yersinia national reference laboratory since september 1988 . to encompass the whole cold season ,
 numbers in parentheses are mean monthly value over the 17 years in which case numbers were not increased .
rodent populations tend to increase with ongoing changes in agricultural practices , e.g. , removal of farmland hedges ( which provide shelter for the rodents predators ) and reduction in pesticide use .
hence , the dynamics of the wild rodent population and reduction in pesticide use may represent a useful predictive marker for the occurrence of new outbreaks .
the surveillance and control of the small mammal population might help limit the incidence of pseudotuberculosis and other wild rodent  borne diseases of humans in france .
 cases of yersinia pseudotuberculosis infection increased in france during the winter of 200405 in the absence of epidemiologic links between patients or strains . 
 this increase represents transient amplification of a pathogen endemic to the area and may be related to increased prevalence of the pathogen in rodent reservoirs . 
The Study
Conclusions