Focus on... Tick-borne diseases DS20-INTGB - June 2017 With an increase in forested areas, The vector: ticks an increase in the number of large mammals, and developments in forest The main vector of these diseases are use and recreational activities, the hard ticks, acarines of the Ixodidae family. In France, more than 9 out of 10 ticks incidence of tick-borne diseases is on removed from humans are Ixodes ricinus the rise. and it is the main vector in Europe of human-pathogenic Lyme borreliosis (LB) In addition to Lyme disease, which has spirochaetes, the tick-borne encephali- an estimated incidence of 43 cases tis virus (TBEV) and other pathogens of per 100,000 (almost 30,000 new cases humans and domesticated mammals. identified in France each year), ticks can It is only found in ecosystems that are transmit numerous infections. favourable to it: deciduous forests, gla- des, and meadows with a temperate Although the initial manifestations of climate and relatively-high humidity. these diseases are often non-specific, Therefore, it is generally absent above a they can become chronic and develop height of 1200-1500 m and from the dry into severe clinical forms, sometimes Mediterranean region. with very disabling consequences. They Its activity is reduced at temperatures respond better to antibiotic treatment if above 25°C and below 7°C. As a result, it is initiated quickly, hence the need for its activity period is seasonal, reaching a early diagnosis. maximum level in the spring and autumn. Larva Adult female Adult male Nymph 0 1.5 cm It is a blood-sucking ectoparasite with 10 days. A female tick can ingest up to 3 distinct stages of development: larva, 150 times its weight in blood. At the end nymph, adult. of the meal, the tick detaches from its During its life-cycle, the tick climbs above host and falls to the ground. the herbaceous layer on the lookout for a Several months (between 9 and 12) are host, which it detects using various sen- needed to pass onto the next stage. sory organs on its first pair of legs; these Egg laying (about 20,000 eggs) kills the are sensitive to mechanical, thermal and female tick. chemical stimuli generated by the host. The total duration of the life-cycle is on The blood-meal can last between 3 and average between 2 and 4 years. DS20-INTGB - June 2017 2/12 At each stage Finding a host of the tick's The larvae fall to the development, Hatching of ground and molt the relative size the larvae of the animals Stage 1 host represents their importance as a host. Eggs Nymphs The engorged females fall to the ground Stage 3 host Stage 2 host Blood-meal for females Blood-meal for nymphs Source: EUCALB Man is an accidental host: it is a stage regions, it is the tick most commonly 2 host from which the nymphs (approx. found on dogs (at every stage), and it 2 mm in size) feed. can also bite humans, especially if the infestation is heavy. The distribution of ticks throughout France shows regional disparities, with some areas having higher densities of nymphs, Lyme disease but vector studies are incomplete (data from JF Chapuis, BEH 2010): Lyme disease is the most common 1. Alsace (146 nymphs/100m2) vector-borne zoonotic disease in the 2. Limousin (121 nymphs/100m2) Northern Hemisphere. Monitoring of the 3. Lower Normandy (111 nymphs/100m2) disease is a priority because of its emerging nature and its potential severity. 4. Île-de-France (Essonne) (73 nymphs/ 100m2) The agent responsible is a spiral bacterium of the group collectively known as Borrelia Other ticks involved in the spread of burgdorferi sensu lato, which comprises disease are: many species. B. garinii, B. afzelli and - Dermacentor sp (mainly reticulatus): B. burgdorferi sensu stricto are the main found outside forests, including in European species. urban areas, with activity period that extends until winter; it is the adult, The distribution throughout France is which is more readily identifiable, that consistent with the distribution of the vector. can feed on humans. The incidence of Lyme disease is estimated - Rhipicephalus sanguineus: found at 43 cases per 100,000 inhabitants. in the southern and Mediterranean DS20-INTGB - June 2017 3/12 Estimated mean annual incidence of Lyme disease in France by region 2009-2011 (Sentinelles Network, source: InVS) Incidence per 100,000 inhabitants 0 1 - 28 29 - 65 66 - 89 90 - 157 > 157 1. Transmission of Borrelia to its host spirochetes. Secondly, the interaction Approximately 10 to 20% of ticks are between the salivary protein Salp15 and infected with Borrelia, and the bacterium OspC results in protection from the can be found in all stages of the tick's bactericidal effects of anti-OspC antibodies. development. Suppression of the expression of OspC, which is highly immunogenic, and the When the bacterium is ingested by the over-expression of the protein VlsE, which tick, it produces an outer surface protein has high antigenic variation, constitute (OspA) which interacts with a protein in the essential mechanisms to evade the the gut of the tick (TROSPA): this interac- host's immune response: the bacterium is tion enables the bacterium to attach within not destroyed by the very early anti-VlsE the intestine of the vector and protects it antibodies. from the tick's immune system. Thus, all of these mechanisms allow The bacterium multiplies, then migrates infection of the host and dissemination to from the intestines to the salivary glands. its target organs. Saliva is an essential element in the The risk of Borrelia transmission transmission phase and for the initiation increases with the time that the tick is of the infection. Various mechanisms then attached to the host. The risk is very low contribute to the transmission of Borrelia with an attachment time of less than to the vertebrate host. Firstly, suppression 7 hours, and very high after 48 hours: of the production of OspA and expression primary and secondary preventive of OspC constitute a major virulence measures are therefore essential to factor to enable the transmission of the prevent the transmission of Borrelia. DS20-INTGB - June 2017 4/12 2. Clinical information: the 3 stages of infection and how to diagnose them - European consensus Recommended essential Stages of Clinical forms tests for diagnosis, and Optional tests infection their respective results Early localised Erythema migrans: stage or primary - Bull's-eye rash (≥ 5 cm in phase diameter), with or without a clear centre, developing in a ring, with elevated edges NO TESTS = diagnosis None if lesion is - Spontaneous resolution (up to 6 based on clinical examination typical months without treatment, in a few days on antibiotic therapy) Incubation 7 to 21 Antibiotic therapy helps days prevent complications and progression to the other stages - Lymphocyte reaction Neurological Lyme disease in CSF and/or elevated In adults: protein levels in CSF. - mainly meningoradiculitis, - Positive IgG serology in meningitis; CSF; sometimes delayed in the blood. - in rare cases: encephalitis, PCR on CSF myelitis; - Intrathecal synthesis of specific IgG. In early - in very rare cases: cerebral cases, intrathecal vasculitis synthesis of specific In children, mainly meningitis and antibodies may still be Early facial paralysis. absent at the time of the disseminated initial sample. stage or secondary - Analysis phase Lyme arthritis - Positive serology in the of synovial - Arthritis of one or more large blood, normally with tissue or fluid - Some weeks or joints elevated levels (IgG) months after the - Detection of primary phase - Possibility of recurrence - Inflammatory synovial fluid Bb sl using PCR - Dissemination of the pathogen via Borrelial lymphocytoma - Histological the blood - Painless erythematous or purplish - Seroconversion or positive confirmation blue nodular swelling serology - Detection of - Usually on the lobe or helix of the - Histological confirmation in Bb sl using ear, nipple or scrotum ambiguous cases PCR on skin - More common in children biopsy (especially on the ear) - Histological Multiple erythema migrans lesions - Specific serology confirmation Cardiac manifestations (rare) - Detection of Atrioventricular conduction disorders Bb sl using (first, second or third degree AV - Specific serological testing PCR on block), arrhythmias, sometimes myocardial myocarditis or pancarditis biopsy Late disseminated - Histological stage or tertiary Joint symptoms, neurological confirmation phase and cutaneous symptoms - Specific IgG serology with - Detection of Several months and Acrodermatitis chronica atrophicans elevated levels Bb sl using years after the onset (ACA) PCR on skin of the infection biopsy DS20-INTGB - June 2017 5/12 3. Natural course of Lyme disease presence of the bacterium. Lyme disease occurs following a bite from - the tertiary phase; this phase develops an infected tick: the risk of transmission of late in the absence of treatment, but it the bacterium is estimated at 1 or 2%. can also be the inaugural phase of the If transmission takes place, clinical mani- disease. It is caused by pathophysiolo- festation of the disease is seen in 5% of gical mechanisms where the role of cases. Lyme disease develops in three Borrelia is indirect; the clinical phases: manifestations observed are the result - the primary phase, in which erythema of autoimmune-like reactions associated migrans is the most common with the presence of bacterial molecules manifestation (77-90% of cases); forming antigenic communities with - the secondary phase of dissemination, joint, neurological and cutaneous tissue in which neurological manifestations components. are the most frequent in France (48%), The clinical expression of Lyme disease is followed by joint manifestations (about highly variable. The different phases may 27%). overlap, and progression from one to the In these two phases, the clinical next is not systematic. Furthermore, the manifestations are directly linked to the early phase may be asymptomatic.