Opening the black box of Anaplasma phagocytophilum diversity: current situation and future perspectives

Abstract

Anaplasma phagocytophilum is a zoonotic obligate intracellular bacterium known to be transmitted by ticks belonging to the Ixodes persulcatus complex. This bacterium can infect several mammalian species, and is known to cause diseases with variable symptoms in many domestic animals. Specifically, it is the causative agent of tick-borne fever (TBF), a disease of important economic impact in European domestic ruminants, and human granulocytic anaplasmosis (HGA), an emerging zoonotic disease in Asia, USA and Europe. A. phagocytophilum epidemiological cycles are complex and involve different ecotypes, vectors, and mammalian host species. Moreover, the epidemiology of A. phagocytophilum infection differs greatly between Europe and the USA. These different epidemiological contexts are associated with considerable variations in bacterial strains. Until recently, few A. phagocytophilum molecular typing tools were available, generating difficulties in completely elucidating the epidemiological cycles of this bacterium. Over the last few years, many A. phagocytophilum typing techniques have been developed, permitting in-depth epidemiological exploration. Here, we review the current knowledge and future perspectives regarding A. phagocytophilum epidemiology and phylogeny, and then focus on the molecular typing tools available for studying A. phagocytophilum genetic diversity.

Keywords: Anaplasma phagocytophilum; diversity; epidemiology; granulocytic anaplasmosis; phylogeny; tick-borne fever; typing technique.

Figure 1

Hypothetical epidemiological cycles of A. phagocytophilum variants Ap-ha (A) and Ap-V1 (B) in the USA. In the USA, I. scapularis (Eastern states) and I. pacificus (Western states) are the main vectors of A. phagocytophilum. To date, two predominant independent epidemiological cycles, involving the two different variants Ap-ha and Ap-V1, have been identified in this country. White-footed mice, raccoons, gray squirrels (Eastern USA) and other rodents (Western USA) are reservoir hosts for the first variant, Ap-ha, which also infects humans, dogs, and horses. Variant Ap-V1 circulates in a secondary epidemiological cycle, which involves white-tailed deer as reservoir hosts. Domestic ruminants can be experimentally infected by this variant, however to date, no BGA cases have been reported in the USA. Thus, under natural conditions, variant Ap-ha does not appear capable of infecting ruminants, whereas variant Ap-V1 cannot infect either rodents or humans. Finally, two potential alternative A. phagocytophilum epidemiological cycles have been described in the USA: the first involves N. mexicana and P. maniculatus as reservoir hosts and the tick I. spinipalpis as vector, whereas the second involves the cottontail rabbit as a reservoir host and I. dentatus as vector. In purple, vectors; in red, reservoir hosts; in green, dead-end hosts (or clinical hosts); Large solid arrow, demonstrated transmission; Solid arrow with question mark, unknown transmission.

Figure 2

Hypothetical epidemiological cycles of A. phagocytophilum in ruminants (A) and in humans, dogs, and horses (B) in Europe. I. ricinus is the main European vector of A. phagocytophilum. Several studies suggest that red deer could be reservoir hosts for domestic ruminant variants. Roe deer are unlikely to be reservoir hosts for human, horse or pet variants, nor for domestic ruminant variants. Roe deer may be involved in another epidemiological cycle, and could maintain their “own” specific variant(s). Hedgehogs have been suspected as reservoir hosts for human variants, but this remains unproven. Similar to roe deer, hedgehogs could also be involved in an alternative epidemiological cycle, in which I. hexagonus could be the vector. Different rodent species could be involved in an independent epidemiological cycle involving I. trianguliceps as vector. In purple, vectors; in red, reservoir hosts; in green, dead-end hosts (or clinical hosts); Large solid arrow, known transmission; Solid arrow, unknown, but possible transmission; Dotted arrow, unknown, but unexpected transmission.