Rodentia

Roque, André Luiz R. & Jansen, Ana Maria, 2014, Wild and synanthropic reservoirs of Leishmania species in the Americas, International Journal for Parasitology: Parasites and Wildlife 3 (3), pp. 251-262 : 256-257

4.4. Order Rodentia

Rodents are the most diverse and widespread order of mammals and include several cryptic species that can only be separated by karyotyping ( Bonvicino et al., 2002). The first rodents ( Hystricognathi – caviomorphs) arrived in the Americas (along with primates) from Africa approximately 45 million years ago. The second wave of rodent migration to the Americas (Sciurognathi – cricetids) was much more recent and included an initial establishment in North America ( Flynn and Wyss, 1998). Since their arrival, rodents have diversified widely and may be found in desert, adapted to aquatic media, digging long and interconnected tunnels, and in forest canopies ( Wilson and Reeder, 2005). This taxon is most likely the most studied in terms of infection by Leishmania spp. in both natural and experimental conditions; however, excepting a few studies, experimental infections have been conducted in laboratory mouse lineages, which are not representative of the wild Mus musculus .

After the Pilosa, Marsupialia and Cingulata , caviomorphs (suborder Hystricognathi ) are most likely the most ancient hosts of Leishmania spp. Moreover, their arrival in the Americas is related to the entry of some species from the sub-genus Leishmania into the continent ( Thomaz-Soccol et al., 1993). Caviomorphs from the genus Proechimys were already found to be infected by various Leishmania species. These rodents are characterized by their longevity (more than 3 years in captivity) and high abundance in most localities where they are found in tropical forests of Central and South America ( Ashford, 1996). Various Proechimys species have been identified as potential reservoirs of L. amazonensis in Brazil and French Guiana, as demonstrated by the frequent skin parasitism confirmed by tissue culture ( Arias et al., 1981; Dedet et al., 1989). In French Guiana, for example, this infection was observed in two sympatric species, P. cuvieri and P. guyanensis ( Rotureau, 2006) . Other reports of natural infection in the skin of these rodents include: L. infantum in P. canicollis from Colombia ( Travi et al., 1998a), and L. guyanensis in Proechimys sp. from French Guiana ( Dedet et al., 1989), and Brazil ( Lainson et al., 1981a) ( Table 1).

P. semispinosus from Colombia experimentally infected with L. panamensis developed self resolving non-ulcerated lesions (from which parasites could be re-isolated, and which were demonstrated to be highly infective to vectors in the initial phase of infection ( Travi et al., 2002) . This host–parasite interaction exemplifies a temporal reservoir competence in one host species, passing from an amplifier host (in the beginning of infection) to a maintenance host, in which transmissibility competence is lower. In contrast, the same rodent species experimentally infected with L. infantum developed only subclinical infection and was not infective to vectors, although the authors re-isolated the parasites from the spleen of some rodents during necropsy ( Travi et al., 2002). Other authors have detected no infection in laboratory-bred specimens of another species, P. guyannensis , after inoculation with promastigotes or amastigotes of L. infantum ( Lainson et al., 2002) . This difference may be due to many variables related to the host and the parasite, such as the intra-specific heterogeneity of both taxa and/or the size and route of the inoculum.

Considered monospecific until 2002, caviomorphs from the genus Thrichomys comprise at least five cryptic species distributed across different biomes in Brazil ( Bonvicino et al., 2002). T. apereoides were found to be infected with L. braziliensis , L. guyanensis , L. infantum and L. amazonensis in leishmaniasis-endemic areas in Minas Gerais, Brazil ( Oliveira et al., 2005; Quaresma et al., 2011). Recently, we also detected infection by various Leishmania species in these rodents: L. infantum , L. naiffi , L. braziliensis and L. shawi in T. laurentius , L. shawi in T. inermis and L. naiffi in T. pachyurus (Cássia-Pires et al., unpublished data). Moreover, T. laurentius experimentally infected with L. infantum and L. braziliensis were able to maintain the infection and parasite re-isolation was achieved up to 12 months after infection. Leishmania DNA was detected in all experimental groups and in all tissues sampled, independent of the Leishmania species inoculated ( Roque et al., 2010).

In addition to Proechimys spp. and Thrichomys spp. , L. infantum has been diagnosed in Clyomys laticeps , Dasyprocta azarae , Nectomys squamipes , Holochilus sciureus and Rhipidomys mastacalis from Brazil (Cássia-Pires et al., unpublished data; Dantas-Torres and Brandão-Filho, 2006; Quaresma et al., 2011; Lima et al., 2013;) and Rattus rattus from Brazil and Venezuela ( Quinnell and Courtenay, 2009). Natural infection of Coendu prehensilis , used as sentinels in Bolivia, has been parasitologically confirmed in the liver and spleen ( Le Pont et al., 1989).

Regarding L. braziliensis , if we consider only studies that confirmed the identity of the etiological agent (not considering the ancient L. braziliensis sensu lato), the following rodent species have been described to be naturally infected: Akodon arviculoides , Mus musculus , Nectomys squamipes , Necromys (= Bolomys ) lasiurus , Oryzomys nigripes , Rattus rattus and Sigmodon hispidus ( Brandão-Filho et al., 2003; de Freitas et al., 2012; De Lima et al., 2002; Forattini et al., 1972; Peterson et al., 1988; Rocha et al., 1988; Vasconcelos et al., 1994). In other cases, the authors confirmed infection by the subgenus Leishmania (Viannia) sp. ( Holochilus scieurus and Cerradomys subflavus ) ( Brandão-Filho et al., 2003; Lima et al., 2013) or tentatively identified the etiological agent through the biological pattern of in vitro growth ( Rhipidomys leucodactylus and Proechimys guyannensis ) ( Lainson et al., 1981b).

Rodents are also usually considered as the main reservoirs of Leishmania from the L. mexicana complex ( L. mexicana and L. amazonensis ). L. amazonensis was described in rodents from the following genera: Akodon , Dasyprocta Oligoryzomys , Oryzomys , Proechimys , Thrichomys and Sciurus ( Arias et al., 1981; Kerr et al., 2006; Lainson et al., 1981b; Mimori et al., 1989; Oliveira et al., 2005; Telleria et al., 1999). None of these studies, however, included follow-up of the infection or demonstrated competence to infect vectors.

L. mexicana has been isolated from various species of Neotoma , including a specimen of N. floridana with a large lesion in the ear from which the parasite could be isolated ( Kerr et al., 1995; McHugh et al., 2003). This finding was informative, suggesting that this rodent species may be infective for the vector and an important reservoir of L. mexicana . Ototylomys phyllotis from Belize should be considered as a possible reservoir of L. mexicana because of its relative abundance, prevalence of infection and attraction to Lu. flaviscutellata , the most important vector in the region. Curiously, the same author failed to reproduce this infection under experimental conditions ( Ashford, 1996), possibly due to factors occurring only in nature, such as stress and concomitant infections, which may be important for the establishment of Leishmania infection . This situation highlights the importance of the studies of naturally infected specimens and the difficulties of adopting potential reservoir hosts as alternative models for leishmaniasis studies. Moreover, these findings attest to the hazards of applying conclusions based solely on experimental models to natural systems.

The persistence of L. mexicana infection in wild rodents was demonstrated twice. The first such finding occurred in Mexico, where 29 naturally infected rodents were maintained in captivity and tested monthly for parasites for up to 2 years. In that study, the authors demonstrated persistent infection, including symptomatic infections, in Sigmodon hispidus , Oryzomys melanotis , Ototylomys phyllotis and Peromyscus yucatanicus , the latter two being the most important because of their high relative abundance in local fauna and longer life spans ( Van Wynsberghe et al., 2000). Second, in the United States, during a 19-month mark–release–recapture study of Neotoma micropus , the authors reported the persistence of L. mexicana infection for up to 1 year ( Raymond et al., 2003). Heteromys , Nyctomys and Reithrodontomys were also found infected with L. mexicana ( Ashford, 1996; De Lima et al., 2002; Disney, 1968; Lainson and Strangways-Dixon, 1964; Van Wynsberghe et al., 2009).

Leishmania lainsoni was isolated from fragments of intact skin from pacas ( Agouti paca ) in the Brazilian state of Pará ( Silveira et al., 1991) and from Coendu sp. ( Table 1). Leishmania panamensis was isolated from naturally infected Heteromys dermarestianus from Costa Rica ( Zeledon et al., 1977), while a squirrel Scirus granatensis was found to be infected with L. equatorensis in Ecuador ( Grimaldi et al., 1992). Leishmania peruviana , a species suggested to be a synonym of L. braziliensis , was isolated from the Peruvian Phyllotis andinum ( Llanos-Cuentas et al., 1999). Finally, L. hertigi / L. deanei and L. enriettii , species taxonomically more similar to Endotrypanum than to Leishmania have been described, respectively, in porcupines Coendu spp. ( Herrer, 1971; Silva et al., 2013) and in the guinea pig Cavia porcellus ( Machado et al., 1994) .

Taken together, a broad diversity of Leishmania species naturally infect this mammal group, most likely reflecting the diversity of ecological niches occupied by the hosts. The differences observed among the rodent species include the forest strata they occupy and their reproductive strategies (seasonality, gestation time and number of offspring), and these traits should be considered evaluations of the importance of a rodent species as a Leishmania reservoir. Moreover, as expected for every host–parasite interaction, this heterogeneous mammalian taxon shows a spectrum of competence to maintain and transmit Leishmania from high susceptibility with high transmissibility competence to quick control of infection.