AETIOLOGY AND EPIDEMIOLOGY The term "Lyme disease" is derived from the name of a small town in Connecticut, Old Lyme, where, in 1975, numerous cases of arthritis of suspected infectious origin were detected in the majority of both the adult and paediatric population. The disease has also been described in the European literature since quite some time. The causative agent of Lyme disease was isolated in 1982 by Burgdorfer, a biologist from Hamilton (Montana), from the gut of a tick of the genus Ixodes dammini (now Ixodes scapularis); the microorganism was classified as belonging to the family of spirochetes and was called Borrelia burgdorferi.
In Europe, the most important vector of Borrelia burgdorferi is the Ixodes ricinus tick. Lyme disease is an anthropozoonosis; not only does it affect humans and dogs, but also a large number of wild animals such as deer, raccoons, opossums, squirrels, hedgehogs as well as small rodents that also act as reservoirs of the infection for humans. Other domestic animals can also be infected, notably cattle, sheep and horses.
Initially discovered in the United States, endemic outbreaks of the disease were subsequently found in Canada, Japan, China, Australia and Europe. As an example, in Italy the first case of Lyme disease in a human patient was identified by Crovato in the Liguria region in 1983. In the following years many other cases were reported in practically all Italian regions, with the exception of Valle d'Aosta and Basilicata. The north eastern regions of the Italian peninsula were the most affected, Friuli Venezia Giulia in particular. Currently, Lyme disease is the most frequent tick-borne disease in the United States. In areas endemic for Lyme disease I. scapularis tick-bites are common, being responsible for approximately 80% of all tick bites. In Westchester County, New York, where the disease is endemic, 14,000 victims of I. scapularis tick bites were reported in a single year.
Although the presenceof Lyme disease in Italy was reported early on, just after the initial description of the disease and its aetiologic identification (1983), to date a comprehensive understanding of the epidemiology of the disease in Italy is still non-existent. As the cases of Lyme disease were beginning to become numerous, with a major impact on patients, in 1992 Lyme disease was included within the group of Class 5 notifiable infectious diseases (Italian Ministerial Decree of 15/12/90), and thus became subject to mandatory notification. This notwithstanding, the level of awareness and the search for Lyme disease throughout the country is still uneven and sporadic. The reasons are to be found in the polymorphism of Lyme disease and in a certain difficulty in making the diagnosis. The mandatory notification does not appear to have greatly facilitated the collection of cases, probably in view of the Class in which the disease has been placed.
PATHOGENESIS
Dogs and cats become infected only through the bite of Ixodidae ticks: in the USA via Ixodes scapularis and Ixodes pacificus, in Europe via Ixodes ricinus. Other tick species have sporadically been found to be carriers of B.burgdorferi, but their real transmission potential has never been verified. The Ixodidae responsible for the transmission of the disease are 3-stage ticks (larva, nymph, adult).
In nature, the larvae or nymphs usually become infected by small rodents, with subsequent trans-stadial transmission to the adult. Contrary to other tick-borne diseases (such as piroplasmosis), transovarian transmission has not been confirmed; therefore, larval stages do not appear to be responsible for the infection. Adult Ixodidae show a marked preference for large wild ungulates, which favours the growth of their population, but these are only indirectly responsible for an increased risk of exposure, given the different favourite hosts of larval and nymph stages. Morphology-wise, Ixodidae ticks are characterized by a pronounced rostrum and an anal sulcus which surrounds the anal opening anteriorly and which is visible on the ventral surface of adults and nymphs.
Following their inoculation, the spirochetes of B.burgdorferi penetrate into the host’s connective tissue (not into the blood stream, in which they are not visible) and then disseminate into different sites (in chronic forms usually to the joints), where they become the cause of a persistent, localizedinflammatory response. Spirochete transmission occurs 24-48 hours after the start of the blood meal.
Although experimental studies have shown that the dog may potentially infect ticks, the eating habits of Ixodidae are such that the dog is not considered as a reservoir for B. burgdorferi, but rather a sentinel animal for the detection of its presence in a specific area.
CLINICAL PRESENTATION
The diagnosis of Lyme disease is based on a combination of compatible clinical symptoms and positive serology for B. burgdorferi. Most infected dogs either do not present clinical signs or may exhibit sub-clinical abnormalities. In rare cases fever may be detected, together with painful limbs, with or without oedema, joint effusion, lymphoadenomegaly, or dysorexia-anorexia, which rapidly respond to an appropriate antibiotic treatment. Chronic forms are instead characterized by persistent and progressive polyarthritis unresponsive to antibiotics and sometimes by the presence of protein-losing nephropathy. Neurological alterations (multifocal meningoencephalitis) have only been found in experimentally infected subjects but not in cases of field infection.
Although in some cases protein-losing nephropathy is present, with consequent organ damage, haemocytometry and the biochemical profile are usually normal. The presence of thrombocytopenia or leukopenia is characteristic of a possible Ricketssiae co-infection.
It is important to remember that in the dog the clinical symptoms differ significantly from those in humans, and that the chronic migrant erythema which accompanies the spread of the spirochetes in humans is considered an exceptional event in the dog. To date, in the cat, overt clinical signs of the disease have not been reported in literature.
DIAGNOSIS
Serological assays are a cornerstone in the diagnosis of Lyme disease. In view of the long incubation period, sick dogs are always positive to antibody titration. On the other hand, since in endemic areas a large proportion of asymptomatic subjects are still positive, it is essential to put in close relation symptoms and laboratory tests, so as not to overestimate the problem or to consider B.burgdorferi as the cause of other existing disorders.
Highly sensitive diagnostic kits are available on the market. IFA-based (Indirect Fluorescent Antibody) or ELISA-based (Enzyme-Linked Immunosorbent Assay) assays are not capable of discriminanting between an antibody response in the course of a natural infection from one induced by vaccination. In vaccinated subjects, serial Western blot tests are therefore necessary.
Other diagnostic techniques which are potentially useful in the diagnosis of Lyme disease are the microscopic investigation of tissues, culture tests and PCR (Polymerase Chain Reaction).
The cytologic examination of blood smears is of little use, as only in exceptional cases are the spirochetes of B. burgdorferi detected in peripheral blood. Spirochetes can sometimes be detected in very low concentrations in synovial fluid (dark field microscopy). Bacteriological cultures are of difficult execution as special culture media are required and can give false negative results in view of the low concentration of spirochetes in the samples that are usually collected; the low concentration also limits the sensitivity of molecular diagnostic techniques (PCR).
The IgG antibody response against the whole B. burgdorferi bacterium is usually titratable from 4 to 6 weeks after the infection; the peak is reached after 3 months and the response can persist for many years, even in the absence of re-infections. The IgM antibody response persists for many months; titration of IgM antibodies is of no use in the diagnosis of recent or acute infections.
The antibody titre against the C6 peptide (immunodominant portion of VIsE surface antigen) increases rapidly (after 3 weeks) and is widely used in diagnostic tests. It should however be noted that even in the case of positivity in most dogs acute or chronic clinical symptoms are not present.
In conclusion, to have a reasonably grounded diagnosis of Lyme disease in the dog, all four of the following requirements must be met:
• a history oftick exposure (Ixodidae);
• compatible clinical symptoms;
• positive antibody test;
• rapid response to therapy.
TREATMENT
In overt clinical cases of Lyme Disease, the treatment of choice is based on the oral administration of doxycycline, at a dose of 10 mg/kg per day for 30 days. In case of tick bites, prophylactic treatment is not recommended, given the small incidence of resulting clinical manifestations, even in endemic areas; antibiotic therapy is also not recommended in patients that are seropositive but with no clear clinical symptoms compatible with the disease in question.
PREVENTION
Adjuvanted inactivated vaccines against B.burgdorferi are available on the market; as for their effectiveness, only trials on experimental infections are available. Epidemiological evidence in endemic areas in which they are used poses serious doubts about their effectiveness (in relation to adverse events). In non-endemic areas, their use is not recommended.
The most effective preventive measures are unanimously considered to be those aiming at protecting dogs against tick bites by means of external anti-parasitic agents with antifeeding and/or rapid knockdown effect.
PUBLIC HEALTH CONSIDERATIONS
The dog is not considered as an important species in the transmission of the disease, or as a reservoir; the dog should instead be cosidered as a sentinel, allowing the detection of risk areas for humans. A seropositivity rate greater than 5% in the dog population is associated with a significant risk for human infections; seropositivity rates below 1% define areas not at risk for humans.
Suggested reading
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