Alomst 1,000 species of ticks have been identified throughout the world. Many can transmit pathogens including protozoa, bacteria, and viruses. Infections with single tick-borne pathogens are considered common in people and domestic animals, while the prevalence of infections with multiple tick-borne pathogens is generally unknown. Both people and domestic animals are susceptible to coinfection with tick-borne pathogens, but, relative to single-pathogen infections, comparatively little is known about coinfections. In patients with clinical signs of one tick-borne disease, it is important to consider that they may be infected with multiple tick-borne pathogens. Coinfections may account for the diverse clinical signs some patients exhibit.1
Clinical signs previously attributable to single infections are now being reassessed in light of the awareness of coinfection. For example, epistaxis has not been observed in dogs with experimental Ehrlichia canis infection2-4 but has been reported in dogs seropositive for both E. canis and Bartonella vinsonii subsp berkhoffii.5 This suggests that dogs infected with E. canis and exhibiting epistaxis may be coinfected with Bartonella species.5 Response to treatment, and thus clinical outcome, may be influenced by the presence of additional tick-borne pathogens, so it behooves small-animal practitioners to consider the possibility of coinfections when they suspect or have confirmed that a patient is infected with a tick-borne pathogen.
IMPORTANT TICK VECTORS
In North America, six tick species are important vectors for the more common tick-borne diseases. They differ in their geographic distribution and the pathogens they can transmit (Table 1). Coinfections do not have to be acquired in a single geographic locale. Since some tick-borne infections can be chronic (e.g. ehrlichiosis), a patient's travel history is important in determining exposure to different tick species and tick-transmitted diseases.
Table 1. Tick Species That Are Important Disease Vectors and Their Associated Infective Organisms
MECHANISMS OF COINFECTION
Coinfection with tick-borne pathogens can occur through a number of mechanisms. A single tick species carrying multiple pathogens can transmit more than one organism to the same animal. Researchers in one study using polymerase chain reaction (PCR) testing to determine the prevalence of pathogens in Ixodes scapularis ticks in northern New Jersey documented that a single tick could carry Borrelia burgdorferi, Anaplasma phagocytophilum, Babesia microti, and Bartonella species.6 In that study, 14% of individual ticks surveyed contained more than one pathogen. Other studies have reported lower rates of multiple-pathogen infection in individual ticks.7,8 From these studies, it appears that a small proportion of ticks could individually transmit multiple pathogens to susceptible hosts.
Ticks that are infected with one pathogen do not appear to have difficulty acquiring a second infection. Furthermore, these ticks can successfully transmit both pathogens into a susceptible host. In one study, about 60% of I. scapularis ticks dually infected with Borrelia burgdorferi and A. phagocytophilum successfully transferred both organisms to susceptible mice.9
In some situations, coinfection in the tick may increase the likelihood of transfer of a pathogen from a tick to a host. Ticks feeding on mice coinfected with B. burgdorferi and A. phagocytophilum contained significantly higher numbers of Borrelia spirochetes than did ticks feeding on mice solely infected with B. burgdorferi.10 Furthermore, 50% of ticks feeding on coinfected mice in this study contained evidence of A. phagocytophilum DNA, whereas A. phagocytophilum DNA was rarely detected in ticks feeding on mice infected solely with A. phagocytophilum.10 Although a relatively small percentage of ticks contain more than one pathogen, these ticks may be efficient at producing coinfections.
Coinfection can also be acquired from multiple tick species simultaneously feeding on a host and infecting it with multiple pathogens. This would be more likely in regions in which multiple tick species overlap geographically. Coinfection of animals can also result from the serial transmission of pathogens from multiple ticks at different times.
IMMUNOLOGIC ALTERATIONS AS RISK FACTORS FOR COINFECTION
A possible risk factor for coinfection is an alteration of the host immune responses caused by tick-borne pathogens. In one study, in vitro infection of a monocyte cell line with E. canis caused down-regulation of major histocompatibility complex class II receptors, suggesting presentation of ehrlichial or other antigens to CD4+ T cells; thus the immune responses dependent on such antigen presentation could be compromised.11
Bartonella vinsonii can induce immunosuppression by eliciting defects in monocyte phagocytosis, impairing antigen presentation within lymph nodes, and causing a decrease in circulating CD8+ T cells, which are important for cell-mediated immune responses.12 The effect of these immunologic changes on acquired immune responses could increase the risk of infection with other pathogens, including tick-borne agents, in a host that has compromised immune responses after infection with a single tick-borne pathogen.
Coinfection may have an even more profound effect on immune responses than do single infections. In mice, coinfection with Borrelia
burgdorferi and A. phagocytophilum caused decreased activation of macrophages13 along with other alterations that could skew the immune response toward humoral immunity. These alterations would be of little benefit in eliminating an intracellular pathogen such as Ehrlichia species and could create a favorable environment for Ehrlichia species13 and other tick-borne agents to survive.
Whether immunity is altered in small animals infected with tick-borne pathogens is unclear. One study found that serum IgM, IgG, and IgA concentrations remained unchanged in young dogs after experimental infection with E. canis. In addition, the percentage of circulating CD4+ T cells was similar in infected and uninfected dogs, and functional defects of cell-mediated immunity were not observed.4 Factors that limit studies of the effects of infection with tick-borne pathogens on immune responses include the variability in vectors, differences in pathogenicity among strains, the effect of acute vs. chronic infection, and the wide variation in individual host immune responses. Not to be ignored is the fact that tick-host interaction may also alter the immune reaction. Tick salivary components or intestinal secretions introduced during feeding can shift the immunologic response to a humoral response in the surrounding skin and draining lymph nodes.14