Lyme borreliosis (LB) is the most commonly reported tick-borne infection in Europe and North America. The disease is a multi-system disorder which can affect a complex range of tissues including the skin, heart, nervous system, and to a lesser extent the eyes, kidneys and liver. The illness is caused by a spirochaete (spiral-shaped bacteria), which is transmitted during the blood feeding of ticks of the genus Ixodes.
The term Lyme disease was first used following investigation into a geographical cluster of juvenile rheumatoid arthritis in the town of Old Lyme, Connecticut, USA, in the mid 1970's. Subsequent studies led to the isolation from the deer tick, Ixodes scapularis (dammini) of a gram-negative spirochaete, which was named Borrelia burgdorferi. The disease has, however, been known in Europe under a variety of names (including erythema migrans, acrodermatitis chronica atrophicans, Bannwarth's syndrome) since the 1880's. In 1909, Afzelius had associated a red rash (erythema migrans) with the tick, Ixodes ricinus.
It is now known that LB occurs as a significant disease in thousands of European patients every year.
Borrelia burgdorferi, the causative agent of LB, is a gram-negative, microaerophilic bacterium which belongs to the family Spirochaetaceae. The spirochaete resembles other members of the genus Borrelia morphologically and biochemically. B. burgdorferi is a slow growing, fastidious organism which requires a complex liquid medium and an optimal temperature of 33-35 °C for growth. Glucose provides its major energy source and lactic acid is the predominant metabolic end product. To date B. burgdorferi can be divided into at least 15 genospecies, of which those with pathogenic significance are B. afzelii, B. bavariensis, B. burgdorferi sensu stricto (s.s.), B. garinii.and B. spielmanii. Three further genospecies, B. bissettii, B. lusitaniae and B. valaisiana, may also be pathogenic but firm consistent evidence is lacking. The group as a whole is referred to as B. burgdorferi sensu lato (s.l.).
A large number of tick species have been reported as carriers of B. burgdorferi, however the presence of the spirochaete in questing ticks does not necessarily mean that the ticks are effective in transmitting the disease. In Europe the main vector is Ixodes ricinus, while I. persulcatus is primarily responsible for transmission in Asia. In the Northeastern and the upper Midwestern United States I. scapularis (dammini ) is the main vector, and I. pacificus is the vector in the West of the USA. The process of transmission occurs through salivation during the feeding process on an animal host. The ticks have a three-stage life cycle; larva, nymph, and adult, with the ticks feeding only once during each stage. The vast majority of cases in western Europe are transmitted by the nymphal stage, transmission usually taking place after the tick has been feeding for more than 24 hours. After feeding, the tick will drop off the host and locate on or near the soil surface while they transform to the next stage or, in the case of adult females, lay up to approximately 2000 eggs.
The infection is usually acquired from a reservoir host by larvae or nymphs and transmitted horizontally by nymphs or adults. The abundance of reservoir hosts (usually small and medium sized animals) in a particular habitat is the most important factor in the establishment of significant infected tick populations. Larger animals such as deer, sheep, cows or horses must however be present for the maintenance of the tick population, since adult ticks only engorge successfully on such animals. The larvae and nymphs feed readily on a greater range of hosts, including birds, which may be particularly important as reservoir hosts in areas, such as small islands, that are not accessible to terrestrial animals.
Habitat and Seasonality
In addition to appropriate hosts, vegetation characteristics are also important for the maintenance of tick populations. The non-parasitic (off-host) phases require a high humidity at the base of the vegetation and ideal conditions are to be found in temperate deciduous woodland with patches of dense vegetation and little air movement coupled with high humidity. The need for questing ticks to maintain a stable water balance is an important factor in determining the location and duration of activity. In general, activity will begin in spring and early summer, with ticks being found on vegetation and animals from late March. In habitats where desiccation is high, such as open areas, periods of activity will be shortened to only a few weeks - as opposed to several months in dense woodlands. In some areas a second, less intense, phase of questing activity occurs in the autumn.
Infection can be subclinical (asymptomatic), or have a range of clinical presentations, depending on the tissues affected, the duration of infection, host factors such as the vulnerability of the immune system and immunogenetic factors which could predispose the patient to the development of certain complications. Clinical presentations can generally be divided into three stages but progress from an early to later stage is not inevitable, even if the infection is untreated. The three stages are named early localised LB, early disseminated LB and late (chronic) LB. Many features of LB, especially later infection, are not specific and occur in other conditions.
1. Early localised Lyme borreliosis
In approximately 60% of cases the early clinical feature of LB is erythema migrans, the characteristic red rash or lesion spreading from the site of a tick bite. The EM starts between 2-30 days after a tick bite. The lesion can reach a large size, up to 30 inches (75 cm) in diameter and typically clears from the central area. The affected patient may also have vague 'flu-like' symptoms. The rash may be very faint and not easily noticed, especially if the bite was located in an inconspicuous area. The lesion and 'flu-like' symptoms will resolve even without antibiotics, but it is desirable to treat early localised LB to prevent any risk of possible progression to a later stage.
2. Early disseminated Lyme borreliosis
The organism may spread to other tissues via the bloodstream and lymphatics, and activity can continue for over a year after the initial infection. Manifestations of this stage may include more severe 'flu-like' illness, multiple areas of erythema migrans (usually smaller than the initial lesion), facial palsy, other cranial nerve lesions, aseptic ('viral-type') meningitis, mild encephalitis, arthritis with effusion (joint swelling) and carditis.
3. Late Lyme borreliosis
Progression to this stage is uncommon but may occur in patients who were not treated or inadequately treated at an earlier stage. The most frequently seen presentation at this stage is Lyme arthritis, usually affecting the knee. Other presentations are acrodermatitis chronica atrophicans, an unusual skin condition, and chronic Lyme meningoencephalitis, which is rare.
The diagnosis of LB should be made only after careful evaluation of the patient's clinical history, physical findings, laboratory evidence and exposure risk evaluation. Exposure to ticks prior to disease manifestations is essential for the diagnosis of Lyme borreliosis. Since an awareness or recollection of a tick-bite is not always present, however, this should not exclude the diagnosis of LB.
Laboratory evidence of infection, by demonstration of specific antibodies is not essential for the diagnosis of erythema migrans since a large proportion of the EM patients, especially treated cases, have no antibody response. For all other clinical manifestations of LB, laboratory evidence of infection is essential for the diagnosis. The diagnosis of early and late neuroborreliosis requires demonstration of intrathecal antibody production.
Most infections with B. burgdorferi are asymptomatic and self-limiting, so that individuals carrying antibodies but without clinical symptoms do not require treatment. Patients showing symptoms with adequate supporting laboratory evidence for diagnosis should be treated to prevent possible progression of the disease. A range of antibiotics are available (tetracyclines, penicillin, cephalosporins, etc.) but their selection and use vary in different countries.
The value of the prophylactic use of antibiotics following a tick-bite has been assessed in a number of studies, with mixed results. Since a minority of ticks in endemic areas are infected and infection can be prevented by prompt removal of the attached tick this approach is not generally recommended.
A vaccine for use in humans based on outer surface proteins (OspA) was available in the USA (LYMErix, Smithkline Beecham) until recently, but has now been withdrawn. For an effective vaccine in Europe it will probably be necessary to produce a "cocktail" of such proteins, since European B. burgdorferi are more heterogeneic.
LB in Domestic Animals
The animal reservoir hosts of LB do not seem to show signs of disease when infected with B. burgdorferi s.l., but domestic animals can become victims of this abnormal host/pathogen relationship and sometimes show similar manifestations as occur in humans. Serological studies suggest that infection with B. burgdorferi s.l. is common but at present there is little evidence that LB is responsible for frequent and significant morbidity in any domestic animals, with the possible exception of the dog. Diagnosis of LB in domestic animals is particularly problematic because of the lack of case definitions and of quality-assured laboratory tests.
Tick control is a logical way to disrupt the transmission of LB, but whereas the control of ticks transmitting livestock diseases is relatively straightforward, controlling the vectors of a sylvatic zoonosis, such as LB, is extremely difficult. It is impossible to modify the tick habitat to this end without causing environmental damage and the wild animals that serve as tick hosts are very difficult to target with acaricides. Nevertheless, such approaches have potential on a small localised scale, involving gardens, parks and campsites.
|Last Updated on Sunday, 16 August 2009 21:35|