Relapsing Fevers: Neglected Tick-Borne Diseases

Abstract

Relapsing fever still remains a neglected disease and little is known on its reservoir, tick vector and physiopathology in the vertebrate host. The disease occurs in temperate as well as tropical countries. Relapsing fever borreliae are spirochaetes, members of the Borreliaceae family which also contain Lyme disease spirochaetes. They are mainly transmitted by Ornithodoros soft ticks, but some species are vectored by ixodid ticks. Traditionally a Borrelia species is associated with a specific vector in a particular geographical area. However, new species are regularly described, and taxonomical uncertainties deserve further investigations to better understand Borrelia vector/host adaptation. The medical importance of Borrelia miyamotoi, transmitted by Ixodes spp., has recently spawned new interest in this bacterial group. In this review, recent data on tick-host-pathogen interactions for tick-borne relapsing fevers is presented, with special focus on B. miyamotoi.

Keywords: Borrelia; Borrelia miyamotoi; Ornithodoros; antigenic variations; hard ticks; neurotropism; relapsing fever.

Figure 1

Phylodendrogram of Average nucleotide identity values among RF borreliae genomes. LD Borreliella genomes have been taken as outgroup. The phylodendrogram has been obtained by pairwise comparison of average nucleotide identity (ANI) between two genome sequences of each RF borreliae species sourced from Adeolu and Gupta (2014) and Elbir et al. (2014). Topology created on http://genomes.urv.cat/UPGMA/. The horizontal and vertical lines represent genetic distance, with the scale bar indicating 2% of difference from ANI = 100%. Other related species in SLPA or MLPA based on literature review are: (1) “B. microti,” “B. merionesi” and Ca. B. algerica in the Old world RF group (Naddaf et al., ; Trape et al., ; Fotso Fotso et al., 2015), (2) B. coriaceae and Ca. B. texasensis in the New world RF group (Fukunaga et al., ; Lin et al., ; Naddaf et al., 2012), and (3) “B. lonestari” and B. theileri in the Hard-tick-borne RF group (Lee et al., ; Hagen et al., 2018).

Figure 2

Seasonal (A) and inter-annual (B) RF borreliae transmission to human in Dielmo village, Senegal, from 1990 to 2003. In (A) left panel, the medium red shape in the first graph indicates the congruence between RF borreliae transmission and seasonal rainfall, and the black dotted line in the second graph indicates the 3–4 month phase between both time-series (RF borreliae transmission in blue and rainfall in red). In (B) left panel, the annual incidence density of RF borreliosis is expressed as the number of new infections per 100 persons per year, 95% confidence intervals are indicated and significant differences of incidence are reported by stars (*). In right panels, the schemes expose the likely interpretations for seasonal and inter-annual RF incidence variations, respectively, in relation to the dynamics of the small mammal reservoirs. The reservoir community is represented by a circle, including several dots of different colors as the different small mammal species, and the relative number of dots reflects the relative abundance of each species.

Figure 3

RF increases its persistence in blood by shifting the surface protein Vmp. When antibodies are mounted against the initial serotype (red) all bacteria expressing it are killed by Vmp-specific antibodies. Only those that have shifted to another serotype (yellow) survive and multiply to cause the first relapse. This battle continues until the host dies or the bacteria are eradicated from the blood. Antigenic variation is the mechanism causing the recurring fever which gave the disease its name. Remember that relapses rarely consist of one, single serotype.

Figure 4

(A) Giemsa staing of blood smear of mouse infected by Borrelia crocidurae. (B) Ornithodoros erraticus adult, dorsal, and ventral views.