Louse-borne relapsing fever—A systematic review and analysis of the literature: Part 2—Mortality, Jarisch–Herxheimer reaction, impact on pregnancy

Abstract

Louse-borne relapsing fever (LBRF) is a classical epidemic disease, which in the past was associated with war, famine, poverty, forced migration, and crowding under poor hygienic conditions around the world. The disease’s causative pathogen, the spirochete bacterium Borrelia recurrentis, is confined to humans and transmitted by a single vector, the human body louse Pediculus humanus corporis. Since the disease was at its peak before the days of modern medicine, many of its aspects have never been formally studied and to date remain incompletely understood. In order to shed light on some of these aspects, we have systematically reviewed the accessible literature on LBRF since the recognition of its mode of transmission in 1907, and summarized the existing data on mortality, Jarisch–Herxheimer reaction (JHR), and impact on pregnancy. Publications were identified by using a predefined search strategy of electronic databases and a subsequent review of the reference lists of the obtained publications. All publications reporting patients with a confirmed diagnosis of LBRF published in English, French, German, and Spanish since 1907 were included. Data extraction followed a predefined protocol and included a grading system to judge the certainty of the diagnosis of reported cases. The high mortality rates often found in literature are confined to extreme scenarios. The case fatality rate (CFR) of untreated cases is on average significantly lower than frequently assumed. In recent years, a rise in the overall CFRs is documented, for which reasons remain unknown. Lacking standardized criteria, a clear diagnostic threshold defining antibiotic treatment-induced JHR does not exist. This explains the wide range of occurrence rates found in literature. Pre-antibiotic era data suggest the existence of a JHR-like reaction also in cases treated with arsenicals and even in untreated cases. LBRF-related adverse outcomes are observed in 3 out of 4 pregnancies.

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

“…Thus, a critical appraisal of the incidence of JHR in TBRF is difficult. Nevertheless, compared to LBRF, where we found a JHR incidence rate of 55.8% [4], we found a considerably lower JHR incidence rate of 19.3% in TBRF. Considering the proposed underlying pathomechanisms, the lower incidence of JHR in TBRF may primarily be attributable to the overall lower number of Borrelia in the peripheral blood compared to LBRF [3,236].…”

“…[8]. In 2011, this paradigm changed when Borrelia miyamotoi, a Borrelia species discovered in Japan in 1995 [12], was reported to cause TBRF transmitted by hard ixodid ticks in Russia [4], a finding later confirmed in Europe, Japan and the USA [13][14][15]. Nevertheless, since most TBRF Borrelia are transmitted by soft ticks, several distinct and epidemiological relevant differences between soft and hard ticks deserve to be highlighted.…”

“…Symptoms usually resolve within a few hours. Although JHR is rarely fatal, it is a clinically relevant complication which may require appropriate clinical therapeutic measures [4].…”

“…The reported frequency of JHR in spirochete infections varies widely (Lyme disease: 5-30%, syphilis: 8-75%, leptospirosis: 9-83%, LBRF: 0-100%, TBRF: 1-39%) [42]. However, due to the lack of a uniform definition and a standardised assessment of JHR, reliable data on the true incidence and possible differences in incidence of JHR in spirochete infections remain missing [4]. Thus, a critical appraisal of the incidence of JHR in TBRF is difficult.…”

“…Finally, the advent of molecular diagnostic techniques not only enabled to distinguish TBRF from LBRF, but also significantly changed the understanding of the diversity and epidemiology of TBRF. To summarize the current knowledge on epidemiology and clinical relevant aspects of TBRF we reviewed and analysed the existing literature, analogously to our recently published review on LBRF [3,4].…”