Rickettsia, da Rocha-Lima, 1916

Mendoza-Roldan, Jairo Alfonso, Mendoza-Roldan, Miguel Angel & Otranto, Domenico, 2021, Reptile vector-borne diseases of zoonotic concern, International Journal for Parasitology: Parasites and Wildlife 15, pp. 132-142 : 137-139

3.1.5. Rickettsia

Rickettsia are Gram-negative, aerobic and obligate intracellular bacteria which multiply by binary fission and are associated with invertebrate vectors (Parola et al., 2005). As mentioned before, reptiles participate directly in the epidemiology of some pathogens of both the Rickettsiales order and the Rickettsiaceae family ( Andoh et al., 2015; Novakova et al., 2015). A representative species of Rickettsia of the ancestral group, commonly associated to ticks of ectothermic tetrapods in the Americas, is Rickettsia bellii ( Barbieri et al., 2012; Andoh et al., 2015; Ogrzewalska et al., 2019; Mendoza-Roldan et al., 2021a). This basal clade, seems to have originated from herbivorous arthropods or non-blood feeding hosts, suggesting a horizontal transmission. Indeed, the R. bellii clade is currently linked to arthropod vectors (i.e., ticks) and rarely or unlikely infects vertebrate hosts, thus, demonstrating the cryptic position of this group, and that the vector capacity originated in

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the transitional group of Rickettsia (e.g., Rickettsia akari and Rickettsia australis ) (Weinert et al., 2009). While the pathogenicity of R. bellii to vertebrate hosts is still unknow, most of the Rickettsia species of zoonotic concern, associated to reptiles, are englobed in the Spotted Fever Group (SFG). For example, Rickettsia honei , the causative agent of Flinders Island spotted fever, was first described from Bothriocroton hydrosauri from lizards and snakes (Stenos et al., 2003; Whiley et al., 2016). Other eight species of SFG Rickettsia have been detected in ectoparasites and in reptiles, such as a rickettsial disease in humans, known as African Fever, caused by Rickettsia africae and transmitted by A. variegatum (Parola et al., 1999) . This rickettsial disease has been detected in ticks infesting reptiles imported into North America ( Burridge and Simmons, 2003). Moreover, a species similar to Rickettsia anan was detected in A. exornatum ticks in varanid lizards imported to the USA (Reeves, 2006). In Europe, SFG Rickettsia are represented in reptiles by species such as Rickettsia helvetica and Rickettsia monacensis detected in ticks, such as I. ricinus ( Fig. 1a ) and in blood and tail of lacertid lizards (Mendoza-Roldan et al., 2021b). Other rickettsial species reported in ticks, and in some cases mites, from reptiles are Rickettsia aeschlimannii , Rickettsia amblyommatis , Rickettsia hoogstraalii , Rickettsia massiliae , Rickettsia raoultii , Rickettsia rhipicephali , Rickettsia tamurae and Rickettsia typhi (S´anchez-Montes et al., 2019). Genera of ticks that have been found infected with Rickettsia spp. are Amblyomma , Bothriocroton , Dermacentor , Haemaphysalis , Hyalomma , and Ixodes . On the other hand, mite species recorded positive to Rickettsia spp. belong to the families Ixodorhynchidae , Macronyssidae , Pterygosomatidae and Trombiculidae (S´anchez-Montes et al., 2019; Mendoza-Roldan et al., 2021a). Molecular diagnosis of Rickettsia spp. in reptile tissues has been achieved only in Europe in lacertid lizards from the genus Lacerta (e.g., L. agilis and L. viridis ) and Podarcis (e.g., Podarcis muralis and Podarcis siculus ) (S´anchez-Montes et al., 2019; Mendoza-Roldan et al., 2021b). An important role of reptiles in the epidemiology of rickettsial agents is given by the international reptile trade, where reptiles are imported with their ectoparasites harboring Rickettsia spp. ( Burridge and Simmons, 2003; Pietzsch et al., 2006; Mihalca, 2015; Barradas et al., 2020; Bezerra-Santos et al., 2021a, 2021b). In fact, given that some tick species that usually parasitize reptiles can also infest humans, the risk of emergence of rickettsial agents in non-endemic areas exists (Norval et al., 2020).

3.2. Protozoa

Vector-borne protozoa associated to reptiles are represented by hemoparasites (i.e., plasmodiids, hemogregarines, and trypanosomatid flagellates), which have a greater diversity than those of mammals and birds. The higher diversity in species associated to reptiles could be due to their isolation and the ancestral features of ectothermic tetrapods (Telford, 2009). Nonetheless, those of zoonotic concern associated to reptiles belong solely to the family Trypanosomatidae (Poinar and Poinar, 2004a) . Importantly, Trypanosoma brucei , the causative agent of sleeping sickness, was detected in monitor lizards from Kenya (Njagu et al., 1999). Incidentally, this group of lizards has been pointed out as wild hosts for the tsetse fly ( Glossina fuscipes fuscipes ) in Uganda (Waiswa et al., 2003). Accordingly, experimental evidence suggests that reptiles could be potential reservoirs of this protozoa (Woo et al., 1969). Furthermore, reptile associated Trypanosoma spp. , especially from snakes, may be vectored by sand flies (Viola et al., 2008). Also, studies indicate that vector-borne Trypanosomatidae represented in the genus Paleoleishmania originated in the early Cretaceous. This genus was found in sand flies from Cretaceous Burmese amber (Poinar and Poinar, 2004a). Other Paleoleishmania species were described from extinct species of sand flies (i.e., Lutzomyia adiketis ) from Dominican amber (Poinar, 2008). In addition, Palaeomyia burmitis was also identified with different stages of a leishmanial trypanosomatid, which had nucleated blood cells of reptilian origin (Poinar and Poinar, 2004b). Despite evidence of Leishmania divergence in the Cretaceous, it is still not clear whether this genus originated from the New or Old World, yet, most likely trypanosomatids may have originated in different localities and at different time points over the past 100 million years (Poinar, 2008). More importantly, different hypothesis suggest that Leishmania spp. spread through the forming continents following the migration of vectors and their hosts. Also, it is hypothesized that definitive hosts of primitive Leishmania most likely were reptiles or primitive mammals (Tuon et al., 2008). The species of Leishmania that infect reptiles belong to the subclade Sauroleishmania , which is a sister group of the pathogenic species of mammalian Leishmania , with around 10 species infecting reptiles (Ovezmukhammedov, 1991). Phylogenetic inference supports the origin of lizard Leishmania from parasites of mammals ( Klatt et al., 2019). Thus, species of Leishmania typical of reptiles could transiently infect mammals and vice versa. For example, Leishmania adleri from lacertid lizards may produce cutaneous leishmaniasis in mammals ( Manson-Bahr and Heisch, 1961; Coughlan et al., 2017). Also, Leishmania tarentolae from geckoes has been molecularly detected in human mummies from Brazil (Novo et al., 2015), and human blood from Italy (Pombi et al., 2020). Additionally, S. minuta ( Fig. 1c ), the putative vector of this Leishmania sp. , has been recently detected feeding from humans, also in Italy ( Table 2) ( Abbate et al., 2020). The role of L. tarentolae infection in protecting mammals against other pathogenic Leishmania spp. needs to be further investigated also considering the promising results of preliminary heterologous vaccination attempts ( Klatt et al., 2019). On the other hand, reptiles could also act as reservoirs of pathogenic Leishmania spp. in areas where primary hosts do not occur or where reptiles and typical hosts live in sympatry. Recent studies have detected pathogenic Leishmania , such as L. tropica , L. donovani and L. turanica in lizards and snakes in northwestern China (Zhang et al., 2019; Chen et al., 2019). Given all of the above, future studies should focus on the role reptiles could have in the epidemiology of leishmaniasis and trypanosomiasis.

3.3. Viruses

Reptiles and amphibians may have an important role as reservoirs or overwintering hosts for viruses, mainly arboviruses. Many species of mosquitoes may feed on reptiles, including medically important anthropophilic species such as Aedes aegypti and Aedes albopictus ( Fig. 1d ; 2d ) ( Bosco-Lauth et al., 2018). In addition, most groups of reptiles (i.e., Testudines, Squamata, Crocodylia) have been found serologically and molecularly positive for various arboviruses (Steinman et al., 2003). In fact, many reptile species are considered reservoirs for other arboviruses such as western and eastern equine encephalites, Venezuelan equine encephalitis, West Nile Virus, and most recently Chikungunya virus ( Burton et al., 1966; Bingham et al., 2012; Bosco-- Lauth et al., 2018). Moreover, given the convergent evolution of hematophagous Diptera and terrestrial vertebrates, blood meal identification has proven that arbovirus vectors may predominantly feed on reptiles ( Cupp et al., 2004; Burkett-Cadena et al., 2008). Importantly, Culex tarsalis mosquitoes may feed on reptiles such as the garter snake, that can maintain the virus of the western equine encephalitis during winter, and then infect other hosts. Thus, snakes maintain the virus during brumation (overwintering). Other viruses that are related to reptiles are the Japanese encephalitis and Zika viruses (Thomas and Eklund, 1962; Oya et al., 1983; Bueno et al., 2016). Furthermore, reptiles could be involved to a lesser extent in the maintenance of Rift Valley fever phlebovirus (Rissmann et al., 2020). Other phleboviruses have been identified in the herpetophilic sand fly S. minuta in France, such as the Toscana virus ( Table 3) ( Charrel et al., 2006).

Finally, Testudo tortoises may serve as primary hosts of H. aegyptium ticks, that have been found as competent vectors of Crimean-Congo hemorrhagic fever (CCHF). This disease is caused by a zoonotic Bunyavirales that is distributed through Africa, the Balkans, the Middle East, and Western Asia ( Kar et al., 2020). While the primary transmission cycle of CCHF is guaranteed by birds, mammals and associated

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Hyalomma marginatum ticks in the western Palearctic, tortoises, along with H. aegyptium tick vectors, play a role in the cryptic transmission cycle (ˇSiroký et al., 2014; Kar et al., 2020).

Figures

Fig. 1. Arthropod vectors associated to reptiles represented by a Podarcis siculus lizard and Tarentola mauritanica gecko and zoonotic pathogens they may transmit. a) Ixodes ricinus tick larva, b) Ophionyssus natricis mite, c) Sergentomyia minuta sand fly, d) Aedes albopictus mosquito. Red lines represent high importance role of transmission, orange line represents medium importance role of transmission, gray line represents mechanical vector and green line represents transmission of nonpathogenic zoonotic microorganisms. Dashed lines represent neglectable knowledge on actual role of vector. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 2. Arthropod vectors that may feed on reptiles. a) Ixodes ricinus larva on Podarcis siculus lizard being collected with tweezers, b) Neotrombicula autumnalis larvae mites on Podarcis siculus lizard, c) female Sergentomyia minuta phlebotomine sand fly, d) Aedes albopictus mosquito.