Tick borne relapsing fever - a systematic review and analysis of the literature

Abstract

Tick borne relapsing fever (TBRF) is a zoonosis caused by various Borrelia species transmitted to humans by both soft-bodied and (more recently recognized) hard-bodied ticks. In recent years, molecular diagnostic techniques have allowed to extend our knowledge on the global epidemiological picture of this neglected disease. Nevertheless, due to the patchy occurrence of the disease and the lack of large clinical studies, the knowledge on several clinical aspects of the disease remains limited. In order to shed light on some of these aspects, we have systematically reviewed the literature on TBRF and summarized the existing data on epidemiology and clinical aspects of the disease. Publications were identified by using a predefined search strategy on electronic databases and a subsequent review of the reference lists of the obtained publications. All publications reporting patients with a confirmed diagnosis of TBRF published in English, French, Italian, German, and Hungarian were included. Maps showing the epidemiogeographic mosaic of the different TBRF Borrelia species were compiled and data on clinical aspects of TBRF were analysed. The epidemiogeographic mosaic of TBRF is complex and still continues to evolve. Ticks harbouring TBRF Borrelia have been reported worldwide, with the exception of Antarctica and Australia. Although only molecular diagnostic methods allow for species identification, microscopy remains the diagnostic gold standard in most clinical settings. The most suggestive symptom in TBRF is the eponymous relapsing fever (present in 100% of the cases). Thrombocytopenia is the most suggestive laboratory finding in TBRF. Neurological complications are frequent in TBRF. Treatment is with beta-lactams, tetracyclines or macrolids. The risk of Jarisch-Herxheimer reaction (JHR) appears to be lower in TBRF (19.3%) compared to louse-borne relapsing fever (LBRF) (55.8%). The overall case fatality rate of TBRF (6.5%) and LBRF (4-10.2%) appears to not differ. Unlike LBRF, where perinatal fatalities are primarily attributable to abortion, TBRF-related perinatal fatalities appear to primarily affect newborns.

Fig 1. Assumed global distribution of TBRF and LBRF, 1950–1969 (Felsenfeld O. Borrelia; Strains, Vectors, Human and Animal Borreliosis. St. Louis: Warren H. Green; 1971[8]).

Fig 2. Microscopical detection of TBRF Borrelia in blood films.

Microscopic images of Giemsa-stained thin blood films (original magnifications ×1’000) showing TBRF Borrelia in a patient suffering from TBRF fever due to Borrelia persica (courtesy of Dr. Veronika Muigg).

Fig 3. Flow diagram of search and selection of eligible publications.

Fig 4. Number of TBRF case studies published from 1906 to 2020.

TBRF, tick borne relapsing fever.

Fig 5. Reported TBRF cases by country and causative Borrelia species.

B., Borrelia. Map created on www.mapchart.net.

Fig 6. Reported TBRF cases caused by unidentified Borrelia species.

TBRF, Tick borne relapsing fever. Map created on www.mapchart.net.

Fig 7. Reported presence of TBRF Borrelia species in ticks and animal hosts in America.

B., Borrelia. Map created on www.mapchart.net.

Fig 8. Reported presence of TBRF Borrelia species in ticks and animal hosts in Africa.

B., Borrelia. Map created on www.mapchart.net.

Fig 9. Reported presence of TBRF Borrelia species in ticks and animal hosts in Europe.

B., Borrelia. Map created on www.mapchart.net.

Fig 10. Reported presence of TBRF Borrelia species in ticks and animal hosts in Asia.

B., Borrelia. Map created on www.mapchart.net.

Fig 11. Relative frequency of signs and symptoms (in %) related to TBRF (n = 152 studies).

TBRF, tick borne relapsing fever.

Fig 12. Number of relapsing fever episodes in studies on TBRF (n = 67 studies).

* Note: Since the number of relapsing fever episodes within single studies was mostly reported as median, an evaluation per case was not possible.

Fig 13. Abnormal laboratory findings related to TBRF (n = 65 studies).

ALAT, alanine aminotransferase; AP, alkaline phosphatase; ASAT, aspartate transaminase; CK, creatine kinase; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; GGT, gamma-glutamyltransferase; LDH, lactate dehydrogenase; TBRF, tick borne relapsing fever.

Fig 14. Complications of TBRF (n = 47 studies).

ARDS, acute respiratory distress syndrome; DIC, disseminated intravascular coagulation; TBRF, tick borne relapsing fever.

Fig 15. Use of different antimicrobial compounds/drugs to treat TBRF as reported from 1930 until today (n = 172 studies).