Epidemiolog y K E Y WORDS Lyme disease, borreliosis, epidemiology, Croatia Epidemiology 1!f' Lyme disease Epidemiowgy of Lyme d-isease J. Lipozenčic and M. Šitum SUMMARY Lyme borreliosis {LB) is the most comrnon tick-borne disease in Europe and North America. LB occurs in aU age groups, with equal prevalence in men and women. In Croatia the spirochete Borrelia burgdorferi {Bb) was first isolated in 1991 at the Department of Dermatology and Venereology, Zagreb University Hospital Center from the skin of a patient with Erythema chronicum migrans {ECM) and was designated as P, Zagreb. In Croatia ECM as an early skin rnanifestation of LB was first described by Forenbacher in 1940, followed by Mohar in 1982, Mareti6 et al. in 1989, Curl 1991, Kansky 1992, Bolanča-Bumber 1997. Šitum described in 1998 in Croatia clinical and laboratory analysis in a group of 148 selected subjects (20 frorn a risk population of forestry workers frorn a non-endemic area, 82 from a risk population of forestry workers from a LB endemic area, and 46 LB affected subjects). In 130 out of 148 subjects with positive tick bite history, clinical manifestation of LB were present in 49 and absent in 81 subjects. Sixty out of 148 study group subjects had a positive I FA test, and 24 had positive PCR test. The LB is very important for dermatovenerologists because of skin manifestations: ECM, lyrnphadenosis benigna cutis {LBC) and acroderrnatitis chronica atrophicans {ACA). The appropriate treatment of ECM as early as possible is of utrnost importance to prevent the possible occurrence of late manifestations of LB {neurological cardiologic and rheumatologic sequelae). Endemic LB areas in Croatia are Central and North Croatia. Introduction Lyme borreliosis (LB) or Lyme disease currently is the most common tick-borne disease in Europe and North America. LB is a multisystem disease caused by the spirochete Borrelia burgdorferi(Bb). Small roclents, heclgehog, birds , cleer ancl vole are natura! Bb reser- voirs, whereas domestic animals (cattle, sheep, dog, etc.) play an important role in the spread of the clisease in inhabitecl areas (1,2). LB is usually transmitted by ticks Acta Dermatoven APA Vol 10, 2001, No 4 --------- ---------- --- --- ------ -12J Epidemiology of' Lyme disease Table 1. Frequency of early manifestation of Lyme clis- ease at Dermatology ancl Venereology Health Care Ser- vices in Central, North ancl East Croatia (1985-1994) Koprivnica 131 25 Karlovac 171 66 Čakovec 0991-1994)• 98 Slavonski Brod (1993-1994) 13 6 Ogulin 112 43 Sisak 101 74 Osijek 216 TOTAL 848 214 In Croatia from 1988 till 1990 in same regions were re- corded 907 cases of ECM *Data obtained _fi"()Jn the Polyclinic .fi,r !11/ectious Diseases (1991- 1994) and Dermatovenerology Service until 1994 from the family Ixodidae (3) . The first description of a patient with LB is attributed to Buchwald, a German, as early as 1883 (4, 5), whereas the association between tick bite and skin changes was first observed by Afzelius, a Swede, in 1909, and Lipschutz, an Austrian, in 1913 (6), who called it e1ythema chronicum migrans (ECM) (7). In 1920, Garini and Bujacloux reported ona patient in whom ECM-like purpura developed at the site of tick bite (8), and in 1930 Helstrom described a patient with e1ythema, fever and meningitis secondary to tick bite (9). In Croatia, ECM, i.e. skin manifestation of LB, was first described by Forenbacher in 1940 (10), followed by Mohar in 1982 (11). In 1972, an increasing number of patients with ar- Table 2. Lyme borreliosis: frequency of infections in the period 1992-1998 (54) Year Patients 1992 93 1993 315 1994 255 1995 268 1996 335 1997 229 1998 248 Population in Croatia - 4.501.149 thritis was recorded in the Lyme district, Connecticut, USA; in 1975, 39 chilclren were affected w ith juvenile rheumatoicl arthritis in the districts of Old Lyme, Lyme and East Haddam, Connecticut. Careful epidemiologic and clinical studies revealed the disease to be due to a tick-borne infection, caused by a penicillin sensitive agent. The disease was named Lyme arthritis (12) . In 1982, Burgdorfer and coworkers from USA iclen- tified and isolated the spirochete from the intestine of the Ixodes dammini tick (2,13). A year later, in 1983, the spirochete was also isolated in Europe f.rom the Jx- odes ricinustick (14). Based on DNA morphology and guanine and cytosine content, according to the classifi- cation of Barbour and coworkers (15), the etiologic agent LB belongs to tbe family Spirochaetaceae, genus Borrelia, species Borrelia burgdorf'eri. Bb is a gram- negative microaerophilic bacterium. In Croatia, Bb was first isolated in 1991 at the De- partment ofDermatology and Venereology, Zagreb Uni- versity Hospital Center, from the skin of a patient with ECM, and was designated as Pl Zagreb (16 a,b). Elec- trophoretic analysis of the Bb protein content revealed six major proteins of different molecular mass (OspA, OspB, OspC, p41, p60 and pl00). Various tick species from the genus Ixodes (bard ticks) of the large family Ixodidae, i.e . Jxodes ricinus in Europe and Ixodes persulcatus in Eurasia transmitting B. afzelii, the cause of early and late skin manifesta- tions of LB, and B. garinii generally causing EM and neuroborreliosis, are tbe main vector in Bb transmis- sion (17). Jxodes ricinus occasionally serves as a vector for B. valaisiana (group VS116) and B. lusitaniae (group PotiB2) , wbich do not cause an overt clinical picture of LB (18). Ixodes persulcatus bas also been found inJapan, transmitting B. valaisiana (19). In north- east USA, Jxodes dammini and Jxodes scapularis usu- ally transmit Bb, which mostly causes early ancl late skin manifestation of LB, arthritis and neuroborreliosis (20, 21). In the western part of the USA, Ixodes pacflicus and Ixodes neotomae (22) serve as vectors for the Bor- relia species DN127 and CA55, which have notyet been associated with any clinical symptoms of LB. Ixodes dentatus, which transmits B. andersoni, a new genomic group ofBb 21038 (23) as yet showing no overt symp- toms of LB (24), bas also been recorded in America. Ixodes uriae, mostly serving as a vector for B. garinii, bas been founcl on tbe northern and soutbern hemi- spbere (25), whereas Ixodes ovatus, a vector far non- pathogenic B.Japonica, is most common inJapan (26). Ixodes cholocyclus (27), Amblyomma americanum (28) and Dermacentor variabilis as representatives of Epidemiology 126 ------- - --- - - - - ------ --- - ---------Acta Dermatoven A PA Vol 10, 2001, No 4 Epidemiology other tick species in highly endemic areas of north-east America are highly infected (29). Ixodes trianguliceps and Ixodes acuminatus have been reported in north- ern France as Bb vectors (30). Other possible vectors include some mosquito and fly species (31). Tick infec- tivity with Bb varies in different geographic regions. So, in the north-east, higbly enc!emic area of USA, tbe per- centage of infected Ixodes dam mini ancl Ixodes scapu- laris ticks is 10% - 50% (32) , wbereas on the west coast with sporaclic occurrence of LB the percentage of in- fectecl Ixodes pacj/icus ticks is 1 % - 3% (33). In Europe, tbe infection rate of Ixodes ricinus ticks ranges from 3% to 45% (4.5% - 30.8% in Germany anc! Switzerland (33, 34), and 23.5% in Slovenia (35)). According to Golubic, 45% of Bb infectecl ticks are found in nortb- west Croatia (18). In the USA, white-leg mice are the main reservoir of Ixodes scapularis (36, 37). In Europe, major reservoirs of Borrelia are small rodents, wood mice, field rnice, yellow-neck rnice, voles and dorrnou- ses (38). Bircls, deer, doe, boar, rabbit (39) and numer- ous dornestic anirnals such as dog, borse, cattle, etc. are also significant reservoirs ofBb. ( 40-43). Ali the three tick species can parasitize on man. Transovarial trans- mission of Bb bas also been reportecl (44); bowever, inheritecl infection naturally occurs in less than 1 % of ticks (45). The life cycle of Bb depends on the trans- stage transmission: from infected nympb to host in early summer, ancl from infectecl bost to larva in late sum- mer. The latter will subsequently become an infected nymph to repeat the cycle in the year to come (46). Bb is mostly found in the tick micl-intestine, however, their systemic presence bas also been reported (38). During the attacbment period, spirocbetes were founcl in the saliva 2-4 clays after contact with the host ( 47), prob- ably being transmittecl by saliva from the salivaiy glands during tick feeding or with gastric content vomit. It has been experimentally demonstratecl that tick has to para- sitize on the bost for at least 24 hours or more to allow for spirochete transmission ( 48). The survival ofBb in a rnosquito is limitecl to 6 clays ( 49). The intestine is con- siderecl to be an optimal environment for the growth of Bb, due to the short lifespan of enterocytes during the tick life cycle (50). The use of ticks as vectors for Bb also has otber aclvantages such as prolonged exposure on a bost with low pathogen content, and simultaneous intake of the patbogenic agent interfering witb tbe bost's int1ammato1y response, e.g., anticoagulants and plate- let aggregation inbibitors (51, 52). In the northwest Croatia, an endemic area for Lyme borreliosis, four genomic B. burgdorferi sensu lato groups were identified in the Ixodes ricinus ticks: B. Epidemio/ogy o{ Lyme disease afzelii, B. garnii, B. valaisiana (group VSS116), ancl B. burgdorferi sensu stricto (1) Šitum in her stucly comprisecl specific enclemic ar- eas of Lyme clisease in Croatia ancl results confirmecl tbat B. afzelii is tbe main causative agent of ECM in tbe stucliecl group from that area.(1) As similar stuclies bave not been macle in otber parts of Croatia, tbere is a clilemma wbether B. afzelii is the causative agent of tbe most frequent manifestation of tbe Lyme clisease - ECM in other parts of Croatia. (1) It is necessary to investigate otber clinical types of Lyme disease such as Lyme arthritis ancl neuroborreliosis in orcler to cletermine whether other Bb genospecies are also includecl in the etiology of extracutaneous types of Lyme clisease. Over the last ten years, tbe Lyme clisease (LD) bas grown into a public bealtb problem, especially in USA and central Europe. Aclclitionally to the skin, joints, heart ancl central nervous system can be involvecl. LB occurs in ali age groups, with equal prevalence in men ancl women. Tbe Lyme clisease is ve1y impor- tant for clermatologists because of the three clescribecl cliseases: ECM, LBC ancl ACA. From 1988 till 1990 in Central ancl Nortb Croatia, whicb are enclemic LB areas, 907 cases of ECM were found (53). Therewere 216 cases ofECM in Osijek (East Croatia) in 1995. Table l. Tbe clata on LB frequency cluring 1992-1998 period in Croatia are shown in Table 2 (54). Conclusion In Croatia are geographic ancl climatic characteris- tics favorable for the life cycle and spreacl of tbe ticks of the Ixocles. (i.e. woocllancl witb bumid climate). En- clemic areas for LB in Croatia are: Central, Nortb ancl East parts. Dermatovenereologists ancl infectologists perform cliagnosis of LB in Croatia. Laborat01y cliagnosis of anti- bodies to Bb using inclirect immunofluorescence (IF) since 1988 and Bb cultivation since 1991 in Department of Dermatology ancl Venereology Zagreb University School of Medicine, in Zagreb. ELISA assay is perform- ing in Department for Infectious Disea~es Zagreb. An appropriate treatment of ECM is important in prevention of possible occurrence oflate LB manifesta- tion. Proper eclucation of general practitioners ancl close collaboration witb clermatovenerologists is necessa1y for health care ancl prevention in enclemic areas. Acta Dermatoven APA Vol 10, 2001, No 4 --- - --------------------------- ---127 Epidemiology of' Lyme disease E FE E C E S l. Šitum M. Dijagnostika Lajmske bolesti pomoru lančaste polimerazne reakcije istraživanja u Hrvatskoj. University School of Medicine. Doctoral dissertation, 1998: 153. 2. Curl A. Bolesti prenesene i izazvane ubodom krpelja. Acta Derm lug 1991; 18: 123-9. 3. Anderson JE Epizooetiology of Lyme borreliosis. 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