2.1.1. Babesia microti

2.1.1.1. Humans. The first case of B. microti infection in the United States was detected in 1969 in Massachusetts (Western et al., 1970). The epidemiology of human babesiosis in the United States is similar to Lyme disease with the majority of human cases diagnosed in the northeastern and upper Midwestern United States. In January 2011, babesiosis became reportable in 18 states and one city, and during 2011, 1124 confirmed and probable cases were reported from 15 of the 18 states where babesiosis is reportable (Herwaldt et al., 2012). Most (97%) of cases were reported from seven states (Connecticut, Massachusetts, Minnesota, New Jersey, New York, Rhode Island, and Wisconsin) (Herwaldt et al., 2012). Babesiosis has been reported in asplenic and spleen-intact patients, but disease is most severe in immunocompromised patients.

Infections resulting from blood transfusions have been reported and are probably responsible for sporadic cases occurring in nonendemic states (e.g., Texas, California, Washington, and Georgia) and countries (e.g., Canada) (Kain et al., 2001). From 1980 to 2010, it is estimated that 70–100 transfusion–transmitted infections occurred in the United States (Leiby, 2011). Within highly endemic areas (Connecticut, New York, and Massachusetts), seroprevalence among blood-donors ranged between 0% and 4.3% and importantly, over 50% of seropositive patients were PCR positive (Popovsky et al., 1988; Krause et al., 1991; Linden et al., 2000; Leiby et al., 2002, 2005; Johnson et al., 2009, 2012).

2.1.1.2. Reservoirs. In the eastern US, where the incidence of human babesiosis is highest, the primary reservoir is the white-footed mouse (Peromyscus leucopus) (Anderson et al., 1991; Telford and Spielman, 1993; Stafford et al., 1999). However, infections with morphologically similar Babesia have been reported in other rodents that are sympatric with P. leucopus (e.g., meadow voles (Microtus pennsylvanicus), short-tailed shrews (Blarina brevicauda), brown rats (Rattus norvegicus), Eastern cottontail rabbits (Sylvilagus floridanus), and Eastern chipmunks (Tamias striatus)) (Healy et al., 1976; Spielman et al., 1981; Anderson et al., 1986, 1987; Telford et al., 1990). In general, prevalences in reservoir hosts are high (>25%) (Healy et al., 1976; Spielman et al., 1981; Anderson et al., 1986). A recent study by Hersh et al. (2012), described the reservoir competence for a suite of potential hosts by collecting engorged I. scapularis larvae and testing resulting nymphs for B. microti. Two strains of B. microti were detected in the nymphs, one was a strain associated with human infections, but the other was genetically unique and only found in nymphs from opossums (Didelphis virginiana), raccoons (Procyon lotor), and a single wood thrush (Hylocichia mustelina). For the B. microti strain associated with human infections, the white-footed mouse had the highest reservoir competence (average of 29.5% of ticks became infected) followed by short-tailed shrews and eastern chipmunks (averages of 21.9%, and 17.6%, respectively). Interestingly, masked shrews (Sorex cinereus) also infected a high percentage of ticks, but only a limited number of ticks and hosts were tested.

In Maine, where I. scapularis is absent or rare, a B. microti that was genetically distinct from human-infecting strains was detected in a redback vole (Clethrionomys gapperi), a masked shrew (S. cinereus), and a short-tailed shrew (Goethert et al., 2003). Interesting data from England and Japan suggest that shrews (Sorex spp.) are important hosts; however, few studies have been conducted on US Sorex spp. (Burkot et al., 2000; Goethert et al., 2003; Zamoto et al., 2004b; Bown et al., 2011) Many of these B. microti reservoirs are also competent reservoirs for two other zoonotic pathogens, Borrelia burgdorferi and Anaplasma phagocytophilum, so coinfections of reservoirs and ticks are common (Magnarelli et al., 2006; Abrams, 2008; Tokarz et al., 2010). Experimental or field-based studies are needed to better understand the reservoir competence of rodent species for B. microti in the Northeastern US.

Infections with B. microti, based on either morphology or PCR analysis, have been reported in rodents in the western and southeastern US where B. microti -associated human babesiosis is not known to be endemic. Recently, a high prevalence of B. microti (genetically similar to human-associated strains) was detected in cotton rats (Sigmodon hispidus) in Florida (Clark et al., 2012). In Alaska, B. microti (genetically distinct from human-associated strains) has been detected in Northern red-backed voles (Myodes (Clethrionomys) rutilus), tundra voles (Microtus oeconomus), singing voles (Microtus miurus), shrews (Sorex spp.), and Northwestern deer mice (Peromyscus keeni) (Goethert et al., 2006). In Colorado, B. microti was identified in 13 of 15 prairie voles (Microtus ochrogaster) by PCR of blood or spleens (Burkot et al., 2000). Similarly in Montana, nearly half of all montaine voles (Microtus montanus), meadow voles, and water voles (Arvicola richardsoni) tested by blood or spleen smears were infected with B. microti, whereas none of 40 deer mice (Peromyscus maniculatus) were infected (Watkins et al., 1991). Uncharacterized Babesia spp. have been detected in rodents from Wyoming and California (Wood, 1952; van Peenen and Duncan, 1968; Watkins et al., 1991). B. microti from microtine rodents in Alaska are phylogenetically related to strains detected in other rodent species in Montana and Maine, but these parasites were distinct from human-associated B. microti strains from the United States, Asia, and Europe (Goethert et al., 2006). Therefore, the finding of B. microti (based on morphology) in rodents in a particular geographic area might not suggest a high risk of human infection. As additional evidence that genetic characterization is needed, a small piroplasm from dusky-footed woodrats (Neotoma fuscipes) in California was shown to be a Theileria species (Kjemtrup et al., 2001).

2.1.1.3. Vectors. In the United States, the primary vector responsible for transmission of B. microti to humans is I. scapularis. Other rodent-associated Ixodes species (e.g., I. angustus, I. eastoni, I. muris, and I. spinipalpis) are known or suspected sylvatic vectors of the parasite, or genetically related strains (Watkins et al., 1991; Burkot et al., 2000; Goethert et al., 2003; Tokarz et al., 2010). These other Ixodes spp. are primarily nidicolous and are considered low risk for transmission of B. microti to people, but rare reports of human infestation have been reported (Anastos, 1947; Damrow et al., 1989; Zeidner et al., 2000). Infection rates for adult I. scapularis in the Northeastern and Midwestern United States are typically low (<3%), although rates as high as 30% have been reported (Steiner et al., 2008; Walk et al., 2009; Tokarz et al., 2010). Nymphs and adult I. scapularis can transmit B. microti to humans but transmission takes at least 48 hours of feeding, so prompt removal of ticks can prevent transmission (Piesman and Spielman, 1980; Johnson et al., 2009). Transovarial transmission has not been proven for B. microti, (Oliveira and Kreier, 1979; Walter and Weber, 1981), but results from Hersh et al. (2012) suggest it may occur for some strains as Babesia positive nymphs resulted from larvae that engorged on opossums and passerine birds which are not known to be hosts for B. microti.