Causes
Lyme disease is transmitted by ticks, hematophagous arthropods belonging to the order Ixodida (Ixodidae family). The causative agent of Lyme disease was isolated for the first time in a tick of the genus Ixodes in 1982 by Willy Burgdorfer, after whom this agent, Borrelia burgdorferi, is named. It is a gram-negative bacterium (genus Borrelia, family Spirochaetaceae). Many other Borrelia species may be transmitted by ticks. Some can also cause Lyme borreliosis. These Borrelia bacteria are included in a complex known as Borrelia burgdorferi sensu lato (Bbsl), which is distinguished from the bacterium isolated in 1982 known as Borrelia burgdorferi sensu stricto (Bbss).
There are at least 20 Bbsl species, which can be divided into two groups:
- those with proven pathogenicity (at least 9 species including Bbss, B. afzelii, B. garinii);
- and those that have not yet been isolated in humans (e.g. B. americana, B. japonica).
Genetic diversity among species in the complex is high, and therefore levels of severity differ and varied organs are affected (i.e. varied organ tropisms). There are also numerous genetic variations within the Bbss species.
Transmission
In Europe, Bbsl species are mainly transmitted by Ixodes ricinus, a vector species that is widespread throughout except for in the Mediterranean basin and high-altitude regions. This hard tick is an exophilic species inhabiting various types of environments (forest, wooded pasture, gardens) offering microclimatic conditions conducive to its survival and easy access to hosts. The life cycle of the Ixodes tick comprises 3 developmental phases.
- The first two phases (larva and nymph) are asexual. During each of these phases, a single blood meal is taken from a vertebrate host, enabling transition to the next phase. In the third developmental phase, which is sexual, females engorge, lay eggs and subsequently die. Hosts cover a broad spectrum including birds, rodents and deer. Given the low probability of bacterial transmission from infected female ticks to their eggs, disease transmission is not considered possible in the larval phase. However, larvae can potentially acquire the bacterium during their first blood meal from a reservoir host (rodents and birds). Although highly susceptible to the disease, humans and dogs are merely accidental hosts incapable of transmitting the bacterium to ticks.
- During the second blood meal, enabling transition from the nymph phase to adulthood, bacteria already present in the nymph’s digestive system pass through the intestinal barrier, reach the salivary glands, and are transmitted to hosts on which the ticks engorge. Nymphs present a high risk of bacterial transmission if infected as they are small and therefore go unnoticed on the skin and can be mistaken for moles.
A positive correlation has been repeatedly demonstrated between infected vector density and human disease incidence in a given region.
Symptoms in humans and diagnosis
The disease progresses in three stages: the early localized, early disseminated and late disseminated stages.
The early localized stage is characterized by erythema migrans (a rapidly expanding red blotch on the skin around the bite measuring 5cm or over) at the inoculation site. This is the most common symptom (observed in approximately 80% of cases).
Complications affecting the nervous system (paralysis, radiculitis), joints (arthritis), heart or skin (acrodermatitis chronica atrophicans) may occur in the early disseminated and late disseminated stages of the disease, but only if the disease is not treated in its early stages.
Onset of the early disseminated stage occurs several weeks after the skin rash. However, its clinical presentation varies significantly among patients. The late disseminated stage marks chronic progression of the disease. This stage is chiefly characterized by symptoms affecting the joints, skin and nervous system.
Although the disease is not fatal, it may leave patients with debilitating sequelae if not treated.
Erythema migrans is a diagnostic marker and no additional laboratory testing is required. The disease is diagnosed based on a clinical assessment supported by laboratory tests during the early disseminated and late disseminated stages of borreliosis. An ELISA (enzyme-linked immunosorbent assay) is generally prescribed to detect immunoglobulins directed against the bacteria and should be followed by a western blot if positive.
Epidemiology
Lyme borreliosis is a disease observed in the northern hemisphere (North America, Europe, Asia).
In Europe
Only an approximate estimate of Lyme borreliosis incidence in Europe is possible, since reporting of the disease is not compulsory in most countries. In a recent literature review, a mean annual incidence of 85,000 cases was estimated. In France, annual incidence was 53/100,000 between 2009 and 2017 according to the Sentinelles network. The annual incidence of cases consulting in general medical practices in 2019 was 76 cases/100,000 population.
The risk of infection is dependent on geographical area, ecological factors and frequency of human outdoor activities. The number of human Lyme borreliosis cases varies over the course of the year, with high levels observed between spring and autumn, which correlates well with ticks’ life cycle.
In the United States and Asia
According to a recent estimate, the annual number of cases in the United States is 476,000 (Centers for Disease Control and Prevention, 2021). Fourteen states, all in the Northeast, Mid-Atlantic and Upper Midwest account for 95.7% of confirmed cases.
The infection has also been reported in several Asian countries including China, Korea, Japan, Indonesia, Nepal and eastern Turkey.
Treatment and prevention
The only current means of treating borreliosis are antibiotics, which exhibit rapid efficacy if the disease is diagnosed sufficiently early. Antibiotic doses are determined by the patient’s age, medical history, allergies and state of health.
No vaccine exists for Lyme disease. Only non-specific prophylactic measures are recommended such as: wearing long clothing and light colors so that ticks can be spotted easily during outdoor activities; using repellents (with due attention to any contraindications); avoiding tick-infested areas; performing thorough checks on returning from walks; and eliminating any attached ticks as quickly as possible. Individuals bitten by ticks should be monitored for 4 to 8 weeks.
At the Institut Pasteur
The Arbovirus Group in the Environment and Infectious Risks Unit researches the infectivity and transmission speed of various bacterial strains of Borrelia burgdorferi sensu lato causing Lyme borreliosis subsequent to tick bites. This research has demonstrated that European Borrelia species are transmitted much more quickly than American species, suggesting a higher risk of infection following bites by infected ticks if these are not removed in time. Its expertise in this area has prompted collaboration with French companies working to improve human and animal health.
July 2021
