29 | 04 | 2017
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Epidemiology of European Lyme Borreliosis

(see also ‘BIOLOGY: LB Transmission and ‘PREVENTION AND CONTROL: Lyme Borreliosis Risk Assessment’)

 

Introduction

Lyme borreliosis (LB) has been reported throughout Europe where it is the most common tick-borne infection, as it is in the USA. Recent studies (2002) show that reported incidence in several countries increased markedly over the previous 10-20 years, for example in Germany, the Netherlands and the United Kingdom (Fülöp & Poggensee 2008. Parasitol Res. 103 Suppl 1:117-20; Hofhuis et al. 2006. Euro Surveill. 22:11 E060622.2 E060629.5; Smith et al. 2000. Emerg Infect Dis. 6:404-7 and HPA/Lyme borreliosis website.2008). A large part of this increase can be attributed to heightened awareness of the condition resulting in increased diagnosis and reporting, and t is also known that overdiagnosis still occurs.There has been  a genuine increase in transmission rates in some regions (Kampen et al., 2004. Appl Environ Microbiol. 70:1576-82), so LB should be regarded as a continuing emergent disease.

Public perceptions of the disease in Europe have been distorted by the media and by activist groups, with exaggerated claims of pathogenicity and of difficulties of diagnosis and treatment. While it is true that LB sometimes presents diagnostic and treatment problems, many of the misconceptions result from misdiagnosis of Lyme borreliosis in patients who have other conditions. Thiscan occur because clinical presentations of LB are not unique to that infection, and also because inadequately standardized and quality-controlled diagnostic methods are used in some laboratories.

Diagnosis is clinical in the first instance, taking into account the risk of tick bite and the symptoms and findings on physical examination. Supporting evidence for a diagnosis of disseminated or late stage disease must be provided from results of laboratory investigations, usually antibody tests.

Infection may be asymptomatic (sub-clinical infection).  Clinical presentations of Lyme borreliosis (symptomatic infection) usually affect the skin, nervous and musculoskeletal systems and rarely the heart. Erythema migrans (EM), the characteristic rash which may appear some days to weeks following infection, is the most common manifestation (approx. 60-80% of cases), neuroborreliosis occurs in approximately 20% of case, arthritis in approximately 10% and carditis is rare. The most feared complication of LB, late neuroborreliosis, is very rare in Europe. Very few deaths associated with LB have been reported in the medical literature.Most have resulted from heart block, which is a relatively rare (or uncommon) manifestation of the disease. Recurrence of disease is known to occur and the majority of these are probably due to reinfections, though relapses also occur. (Alternatively: Re-infections can occur, as immunity following previous infection can wane with time. There is no good evidence for congenital infection with B. burgdorferi  s.l. (Stanek and Strle 2003. Lancet 362:1639-47).

Most patients diagnosed with “chronic Lyme disease”, both in Europe and the US, either show no objective evidence of current or previous infection with B. burgdorferi s.l. or are patients suffering from post-Lyme disease syndrome, which is probably an immune-mediated phenomenon (Marques 2008. Infectious Disease Clinics of North America 22: 341-60, Feder et al.  2007. New England of Medicine  357:1422-30, Oksi et al. 2007. Eur J Clin Microbiol Inf Dis. 26:571-81).

The different manifestations of LB do not show an even geographical distribution, which is probably due to the uneven distribution of the different B. burgdorferi genospecies. Only one of them, B. burgdorferi sensu stricto, has been implicated as the cause of disease in North America, but in Europe five genospecies, B. afzelii, B. garinii, B. burgdorferi sensu stricto, B. bavariensis and B. spielmanii are known to be pathogenic. Others such as B. valaisiana and B. lusitaniae and the rare B. bissetii are of unknown pathogenicity at present, though all have been detected rarely in human cases (Diza et al. 2004. Emerg Infect Dis. 10:1692-3, Lopes de Carvalho et al. 2008 Clin Rheumatol. 27:1587-91, Rudenko et al., 2008. J Clin Microbiol. 46:3540-3).

B. burgdorferi  s.s. is strongly associated with both neurological and arthritic complications, B. afzelii seems to be associated with the degenerative skin condition, acrodermatitis chronica atrophicans, and B. garinii with neurological symptoms (Van Dam et al. 1993. J Clin Dis. 17:708-17)-,butthese associations are not clear-cut and there is considerable overlap. B. garinii predominates in western Europe and B. afzelii becomes more prevalent in northern, central and eastern regions, while there is some evidence that B. burgdorferi s.s. has been introduced from the west (Saint Girons et al. 1998. Zentralbl Bakteriol. 287:190-5; Rauter & Hartung. 2005. Appl Environ Microbiol. 71:7203-16).

The seasonal occurrence of early LB cases is linked closely to that of the feeding activities of the vector tick, Ixodes ricinus (see tick activity graphs on this page). Thus the seasonality of EM is determined primarily by the activity pattern of nymphal and adult ticks and is further influenced by the propensity of people to engage in outdoor pursuits in early summer (see seasonal disease manifestation graphs). The seasonality of slightly later manifestations such as acute neuroborreliosis is less related to tick activity and that of late stage LB (Lyme arthritis, ACA and late neuroborreliosis) is independent of tick activity patterns.

 

European LB incidence

Few countries have made LB a compulsorily notifiable disease, therefore it is possible to make only approximate estimates of LB incidence in Europe. In most countries reporting is mainly conducted through diagnostic laboratories reporting on the available details of patients with positive tests. There are several drawbacks involved in using such systems for the estimation of European LB incidence, including under-reporting of EM, varying patterns of test referrals, varying serodiagnostic criteria and seropositivity linked to past exposure. Within these limitations it is possible to gain useful information from individual countries’ systems through year-to year comparisons of within-country data.

Prospective clinically based studies yield the most accurate information on incidence. However, these are more costly in time and resources than indirect methods, which may represent the only means to carry out surveys in some areas. Indirect methods may include the measurement of the abundance of Ixodes ricinus ticks, the prevalence of B. burgdorferi-infected ticks and seroprevalence studies. All of these indirect measures have weaknesses as indicators of Lyme borreliosis, but at present human seroprevalence studies probably represent the best method to obtain epidemiological data throughout Europe. Taking the limitations of seroprevalence methods into account, it is clear that LB shows a gradient of increasing incidence from west to east with the highest incidences in central-eastern Europe (see Table 1), A gradient of decreasing incidence from south to north in Scandinavia and north to south in Italy, Spain and Greece has also been noted.

 

Table 1. Estimated average Lyme borreliosis annual incidence (over 10 years) in selected European countries (based on Lindgren and Jaenson, 2006, Lyme borreliosis in Europe: influences of climate and climate change, epidemiology, ecology and adaptation measures, WHO Regional Office for Europe, ISBN: 9289022914)

Country

Average annual incidence per 100,000 population

Average number of cases per year

Austria

130.0

14,000

Bulgaria

55.0

3,500

Czech Republic

29.0

2,962

Estonia

35.0

500

Finland

12.7

700

France

16.5

10,022

Germany

25.0

20,700

Ireland

0.6

30

Latvia

16.0

3,680

Lithuania

25.0

8,500

Netherlands

43.0

4,890

Norway

2.8

128

Poland

4.8

1,832

Switzerland

30.4

2,264

Slovakia

18.4

1,000

Slovenia

155.0

3,096

Sweden (south)

80.0

7,223

United Kingdom

0.7

423

It should be noted that since the prevalence of LB appears to be increasing in some areas recent annual incidences are likely to be higher than in the 10-year averages presented above.  It should also be noted that since some countries may not be using standardized laboratory diagnostic tests or widely agreed case definitions some data may be subject to considerable error.

 

Risk groups

Seroprevalence and disease incidence rates are increased in certain occupational groups, e.g. forestry workers, some recreational groups such as orienteers and tourists to high-endemic areas. However, identification of high-risk groups is not always straight-forward and confounding factors are evidently present. For example, Swedish orienteers, who are thought to be regularly exposed to ticks, have been shown to have similar seroprevalences to the general population despite the relatively high prevalence of the disease in that country (Gustafson et al. 1993. Scand J Infect Dis. 25:605-11), and in Ireland, park rangers who are frequently exposed to ticks in areas where the disease is present, have been found to be seronegative  (Robertson et al. 1998. Zentralbl Bakteriol. 288:293-301)

Gender appears to influence seroprevalence and disease incidence rates and most studies report higher rates for males. This is presumed to be due to higher occupational risk and outdoor recreational activity. However, it is interesting to note that in a recent Swedish study on recurrence of erythema migrans (4% of all cases) the majority were recorded in middle-aged women (Bennet et al. 2007. Vector Borne Zoonotic Dis. 7:34-41). The nature of disease manifestations is also influenced by age. Radiculopathy, a relatively common complication in adults, is rarely seen in children, while facial palsy is the most common paediatric neurological manifestation of LB. Acrodermatitis chronica atrophicans, the chronic skin manifestation, mainly occurs in older women and while a specific age-related reactivity is not evident in LB arthritis, most cases occur in adults. Some reports suggest that LB incidence is generally higher in children than in adults in Lyme-endemic areas(?), because of their greater tendency to make close contact with tick habitat (Stanek and Strle. 2003. Lancet 362:1639-47)

 

LB awareness

The most effective preventive measures against LB currently depend on awareness of ticks and the possibility of tick-transmitted infections.. Workers in high-risk occupations and long-term residents of endemic areas are likely to recognise ticks and may have some LB awareness, whereas many other people, especially city dwellers and visitors from non- and low endemic regions, often have little or no knowledge of ticks, and inaccurate perceptions of the disease (Gray et al. 1998. Zentralbl Bakteriol. 28:253-65). Visitors may acquire infection during brief exposure in highly endemic areas and the risk may not be recognised by them or their doctors, so that a proportion of them could go on to develop disseminated or late disease manifestations, which may remain undiagnosed. To combat this, awareness of LB in the general population should be increased throughout Europe, even in areas of low endemicity.

 

Co-infection and co-transmission

Ixodes ricinus, the tick vector of B. burgdorferi s.l., may also transmit other zoonotic organisms (Table 2), some of which may ico-infect with B. burgdorferi s.l. and thus affect LB diagnosis and epidemiology. Patients withco-infections may present with a confusing mixture of manifestations, for example there are reports of tick-borne encephalitis (TBE) cases accompanied by thrombocytopenia, leukopenia and elevated transaminases, which are classic features of ehrlichial and babesial infections (Lotric-Furlan et al. 2000. J. Infect. 40:55-8). Sometimes manifestations caused by different pathogens may overlap sufficiently for one of the infections to be overlooked, resulting in failure to provide appropriate treatment, as in the case of TBE and early neuroborreliosis (Cimperman et al. 1998. Infection. 26:160-4). Serodiagnostic confusion may also arise where cross reactions occur, for example occasional false positive LB serology in ehrlichiosis (Wormser et al. 1997. Am J Clin Pathol. 107:142-7). Some of the zoonotic pathogens transmitted by I. ricinus, such as ehrlichias and babesias, are known to be potentially immunosuppressive and they may affect the severity and duration of infection of co-transmitted pathogens. It is possible that some of the diagnostic difficulties and treatment problems encountered in LB may be due to co-infections with other pathogens.

 

Table 2. Zoonotic organisms potentially co-transmitted with Borrelia burgdorferi s.l. by Ixodes ricinus.

Organism

Disease

Babesia divergens babesiosis
Babesia microti babesiosis
Coxiella burnetii Q fever
Anaplasma spp ehrlichiosis
Francisella tularensis tularaemia
Rickettsia helvetica perimyocarditis, sarcoidosis?
TBE virus tick-borne encephalitis
Last Updated ( Sunday, 16 August 2009 )
 

 

Conclusions

In conclusion it is evident that the prevalence of Lyme borreliosis varies considerably in different European countries, with an overall increasing prevalence from west to east. Information on the distribution of genospecies of B. burgdorferi s.l. (Saint Girons et al., 1998, Zent. bl. Bakteriol., 287:190-5), on the prevalence of infected ticks and on the nature of habitats in LB foci (Gray et al., 1998, Zent. bl. Bakteriol. 287:211-8) show differences within Europe which seem to be relevant to LB prevalence and possibly to the different manifestations encountered. A high level of health professional and public awareness of the variety of clinical manifestations of this disease is desirable for its recognition, treatment and prevention.

 

 

Last Updated on Sunday, 16 August 2009 19:52