Facts about tickborne relapsing fever
Tick-borne relapsing fever (TBRF) is a disease caused by several species of spiral-shaped bacteria (spirochaetes) that are transmitted to humans through the bite of infected soft ticks. At least six TBRF species are known to occur in Europe or close to its boundaries. The greatest endemic risk in Europe lies in the Iberian peninsula, particularly in the Mediterranean part.
The disease is characterised by relapsing or recurring episodes of fever, often accompanied by headache, muscle and joint aches and nausea. The number of relapses is highly variable and the interval between fever episodes ranges from four to 14 days. Reports of death are rare.
Recommended measures to prevent infection include avoiding tick-infested areas (especially during summer months), wearing long trousers and tucking trouser legs into socks, using tick repellents, and using bed nets when sleeping on the ground or camping.
Tickborne relapsing fever (TBRF) is caused by spirochaetes of the genus Borrelia, which includes three main phylogenetic groups: Lyme Borrelia species, New World TBRF Borrelia and Old World TBRF Borrelia, with 17 TBRF species already described. Tickborne relapsing fever is transmitted to humans by Ornithodoros ticks.
Tickborne relapsing fever’s Borrelia species may be found in the blood of their mammalian hosts during febrile periods but rarely between relapses. According to the strain, these pathogens can colonise internal organs like the brain, kidney, liver or spleen, causing emboli and haemorrhagic lesions in tissue capillaries by erythrocyte-aggregation. They may undergo spontaneous antigenic variation on their outer membrane proteins, which is an important immune evasion mechanism that causes disease relapses in humans. Erythrocyte-aggregation is another mode of immune evasion where erythrocyte-covered spirochaetes avoid contact with the immune cells. At least six TBRF species are known to occur in Europe or close to its borders. The greatest endemic risk in Europe lies in the Iberian Peninsula, particularly in the Mediterranean part, and in Asia Minor. Reports of imported TBRF cases have come from the UK, Belgium and France. Tickborne relapsing fever caused by Borrelia species are increasingly reported in travellers from disease-endemic countries. The number of cases is underestimated because most infections are benign, and no diagnosis is made. Tickborne relapsing fever should be considered in all patients returning from the tropics with relapsing fever, especially if no malaria parasites are detected.
Clinical features and sequelae
After the incubation period, which ranges from 3 to 18 days after the tick bite, high fever (>39–40°C) suddenly appears and lasts 3–6 days. Other symptoms include intensive asthenia, headache, arthralgia, myalgia, neck stiffness, stomach ache and nausea. Splenomegaly and hepatomegaly are observed, usually associated with jaundice, and elevated pulse and blood pressure are common. Some patients may present with skin rashes or superficial petechial lesions; haemorrhagic lesions have been reported, especially epistaxis, haematuria and haemorrhagic diarrhoea. Respiratory involvement has been described in the USA. Following the initial fever episode, an afebrile period ensues, illustrating the immune response evasion by Borrelia and causing further relapses. The number of relapses is highly variable (0–15), and they are usually shorter and milder. The interval between fever episodes ranges from four to 14 days.
As a consequence of spirochaetes sequestering in organs and of the high spirochaetaemia, neurologic, arthritic and ocular complications have been described. Neurologic symptoms (2%) are mainly caused by B. duttoni and B. turicatae and include delirium, facial palsy, meningitis, and radiculopathy. Young children and pregnant women may have a more prolonged and serious course of disease, with low birth weight, preterm delivery, spontaneous abortion and neonatal death. Although there is a theoretical risk of death from TBRF, reports of death are rare (0–8%), with the highest rates in patients presenting Jarisch-Herxheimer reaction during treatment.
Ornithodoros ticks are considered the best reservoir of TBRF Borrelia for several reasons: they have an extremely long life span without blood feeding; they have the capacity to harbour TBRF Borrelia for several years; they are able to transmit TBRF Borrelia from tick to tick through trans-stadial, transovarial and venereal modes; and because of hyperparasitism. Numerous vertebrates have been reported to be naturally infected by TBRF Borrelia, but few studies have tested their role as reservoirs. Because of their endophilic characteristics, Ornithodoros ticks commonly parasitise and infect small mammals, birds, reptiles or bats living in their underground habitat.
Tickborne relapsing fever is strictly transmitted by Ornithodoros ticks that are haematophagous at all growing stages. Ornithodoros ticks attach to their hosts for less than one hour, except for some larvae that can stay 1–2 days. During feeding, some Ornithodoros ticks (e.g., O. sonrai) produce local analgesia so that the tick bites are not noticed. Vertebrates and humans become infected through contamination of the feeding site by salivary and/or coxal secretions during the blood meals. Non-treated humans are supposed to be asymptomatic carriers over several years with resurgence of the pathogen and infectiousness during relapses. The persistence of spirochaetes in other vertebrates is quite unknown. Ticks are infected by TBRF during a blood meal on a spirochaetaemic vertebrate (rodent). Borrelia spread in all tissues, including ovaries (responsible for transovarial transmission), salivary glands and excretory organs. Ticks are able to maintain TBRF Borrelia during their whole life span (5–10 years).
Two epidemiological types of TBRF have been described:
- Sporadic TBRF is observed in ‘at-risk’ groups like soldiers, hunters, campers, field workers or travellers through exceptional contact with infected ticks and animal reservoirs during outdoor activities. This type generally occurs or is diagnosed in developed countries.
- Endemic TBRF is caused by rare but regular contact with infected ticks directly living in rural human dwellings, mainly depending on the type of building structures that influences the presence of soft ticks and the capacity for rodent reservoirs to dig burrows. It usually occurs in developing countries.
In both cases, variations of incidence in humans according to age or sex may be due to differential exposure (time spent at home and outside, sleeping habits) or innate receptivity (immunity, congenital transmission).
In countries where TBRF is sporadic, recommended measures should mainly focus on preventing human-tick contact via the following methods: avoiding tick-infested areas (especially during summer months); wearing long trousers and tucking trouser legs into socks; using tick repellents for the skin and an appropriate insecticide for clothing; using bed nets when sleeping on the ground or camping; and increasing the awareness among ‘at-risk’ persons. Contrary to hard ticks, recommending early removal of ticks is inefficient because of their short feeding period and the immediate transmission of the pathogen.
In countries where TBRF is endemic, it is preferable to recommend the removal or the decreasing of tick vectors and natural vertebrate reservoirs from buildings. Additionally, using chemical treatments (rodenticids and acaricids) or natural predators like domestic cats, as well as limiting rodent-friendly environments inside and around buildings, is suggested.
Diagnosis in most disease-endemic areas relies on detection of spirochaetes in blood, bone marrow, or cerebrospinal fluid during a febrile episode. During the primary attack, the observation of spirochaetaemia is possible on thin- or thick-blood smears with dark field microscopy or with conventional staining.
Quantitative buffy coat (QBC) fluorescence analysis has also been described as a very sensitive and specific technique for detecting Borrelia in blood. However, this method requires technical expertise, as well as some laboratory infrastructure, and does not identify Borrelia species. Molecular methods are sensitive and used with increasing frequency. They offer the possibility of species identification, even on samples with very low load of spirochaetes. Specific serological assays are, to date, not available for most of the known TBRFs.
Management and treatment
The recommended treatment for TBRF is tetracycline or doxycycline. When tetracycline is contraindicated, a macrolide antibiotic may be prescribed. Treatment may provoke a Jarisch–Herxheimer reaction within two hours of treatment, caused by massive cytokine release and manifesting as generalised malaise, headache, fever, sweating, rigors, seizures, stroke, tachycardia, diaphoresis, and hypotension.
Key areas of uncertainty
Further research is needed on the vector capacity and competence of different tick species, as well as of the factors determining their introduction and spread in certain areas, like the impact of changes in land use and landscape structure. Further development of diagnostic methods would be helpful in ensuring early diagnosis and treatment.
Note: The information contained in this factsheet is intended for the purpose of general information and should not be used as a substitute for the individual expertise and judgement of healthcare professionals.
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