Saturday, 19 May 2012

Lyme borreliosis in Europe

Eurosurveillance, Volume 16, Issue 27, 07 July 2011

Lyme borreliosis in Europe

A Rizzoli ()1,2, H C Hauffe1,2, G Carpi1, G I Vourc'h3, M Neteler1, R Rosà1

Department of Biodiversity and Molecular Ecology, Research and Innovation Centre, Fondazione Edmund Mach, San Michele all'Adige (Trento), Italy
Both authors contributed equally to this work.
Unité d'Epidémiologie Animale, Institut National de la Recherche Agronomique (INRA), St Genès Champanelle, France

LB risk is specifically linked to tick abundance and exposure. Therefore, although higher risk is no longer considered to be correlated with residency in rural areas, higher LB risk is associated with occupation (e.g. forestry work and farming) and especially with certain leisure activities (e.g. hunting, mushroom collecting and berry picking) and age (with two groups mainly affected: children aged 5–14 years and adults aged 50–64 years).

Since infection is correlated with tick abundance and exposure (and, therefore, tick activity), diagnosis of acute LB peaks in June and July in many northern and central countries of Europe, while a second smaller peak may occur in southern countries in late summer or early autumn; however, both erythema migrans and chronic forms of the disease can be diagnosed throughout the year [3]. Although the number of LB cases seems to be increasing in some areas, such trends are extremely heterogeneous and/or remain to be confirmed [3].

Clinical symptoms
The clinical presentation of LB ranges from acute to chronic illness, with wide variation attributed to the different Borrelia genospecies and/or genotypes implicated in the infection (as described above and in [44]), although the exact mechanisms maintaining chronic symptoms have yet to be confirmed. Diagnosis is primarily clinical and takes into account the risk of tick bite. Clinical case definitions for use in Europe – although not official European Union case definitions – are available in [45].

Briefly, several days or weeks after a tick bite, if Borrelia infection occurs, in 60–80% of cases this will be characterised by erythema migrans (the rash or patch on the skin about 10 cm across that may expand peripherally as a palpable band, and may or may not be itchy) [46], although early infection may be completely asymptomatic. Other early symptoms include influenza-like symptoms, fever, fatigue, headaches and muscle or joint pain. Several weeks or months after infection through a tick bite (with or without a previous history of erythema migrans), neuroborreliosis (noted in 10–20% of symptomatic patients) in the form of meningoradiculitis, meningitis or meningoencephalitis [47], Lyme arthritis or Borrelia lymphocytoma may occur [45]. Less frequently, multiple erythemata, or carditis are diagnosed [45,48]. Months or even years after Borrelia infection, acrodermatitis chronica atrophicans, lymphocytoma, chronic arthritis (fairly rare in Europe), encephalomyelitis or chronic neuroborreliosis (very rare in Europe) may be observed [45].
Microbial or serological confirmation of Borrelia infection is needed for all manifestations of the disease except for typical early skin lesions [49]. The diagnosis of some chronic forms of LB is currently controversial [50], and it has also been suggested that the overdiagnosis and overtreatment of LB may be an important problem [51].

Indirect diagnosis of B. burgdorferi sl
The complexity of the antigenic composition of B. burgdorferi sl and the temporal appearance of antibodies to different antigens at successive time intervals after Borrelia infection means the development of a serological test with high sensitivity and specificity is a challenge. The most commonly used serological methods for the detection of antibodies to B. burgdorferi sl include indirect immunofluorescent antibody assay (IFA) and an enzyme-linked immunosorbent assay (ELISA) [54]. Nevertheless, specific antibodies are often not detectable in the early stage of infection with the use of currently available test methods....


...In more than 50%of cases, diagnosis of LB can be made on the basis of an expanding erythema (confirmed after a one-week follow-up). In the absence of erythema migrans at least one other clinical manifestation must be noted and confirmed using serological diagnosis of Borrelia in blood or CSF. According to the most recent German Society for Hygiene and Microbiology (Deutsche Gesellschaft für Hygiene und Mikrobiologie, DGHM) guidelines [43], serological diagnosis for patients in Europe should follow a two-step procedure: (i) ELISA and if reactive, followed by (ii) an immunoblot, if possible using recombinant antigens (p100, p58, p41i, VlsE, OspC, DbpA), including those expressed primarily in vivo (VlsE and DbpA), instead of whole-cell lysate antigen blots. OspC and VlsE are the most sensitive antigens for IgM antibody detection [54]. European standardisation of these diagnostic tests and new markers for detecting active infections are urgently required [55].



Surprisingly, our review found that there is no European consensus on treatment and that economic considerations and national guidelines on avoidance of drug resistance also impact the current treatment of choice (no comparative costs are available). Treatment of the vast majority of LB cases is based on antibiotics, with drug type, dose, route (oral or intravenous) and duration varying with stage of the disease, as well as with symptoms. Treatment regimes and recommendations are summarised from the regularly updated European Union Concerted Action on Lyme Borreliosis (EUCALB) website [1] and [49], where doses can also be found. See also [49,51,56] for recent reviews on evaluation of treatments.

In general, in almost all LB cases, the disease is resolved with short courses of antibiotics [51,57], although longer courses are recommended for relapses or more serious and/or chronic forms. Some authors advocate that all symptomatic LB cases should be treated in order to avoid progression to later stages of the disease, and suggest that the earlier treatment begins, the less likely it is that more severe forms will follow [58]. However, overtreatment is considered a problem by others [51], although thus far, drug resistance has been noted only in vitro [59]. On the other hand, few data are available on the risk of long-term effects of non-treatment in asymptomatic LB patients [60]. Several studies have now shown that a few so-called chronic or `post-LB' forms of the disease do not respond to antibiotics, although the reason for this is subject to some debate [50,51,61].

The main risks involved in treatment appear to be inappropriate patient management following inaccurate diagnosis. As mentioned above, both over- and underdiagnosis of LB is suspected