Coinfection with multiple tick-borne pathogens - Veterinary Medicine
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Coinfection with multiple tick-borne pathogens
It's not always cut-and-dried—a single tick bite delivering a single pathogen. Sometimes ticks carry more than one infective agent, and sometimes a pet has been bitten by multiple ticks carrying different microorganisms.So when should you suspect that your patient is infected with more than one tick-borne pathogen?


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PCR testing

PCR testing is useful for detecting and differentiating among tick-borne diseases. When serologic testing is inconclusive, PCR testing may help confirm a diagnosis. However, PCR testing generally should be an adjunct and not the sole means of detecting infection. PCR results do not always correlate well with serology, and, in most instances, infection is documented with serology and not PCR testing.

In a study evaluating serologic (IFA) and PCR evidence of coinfection in dogs from Thailand, only 10 of 36 dogs seroreactive to E. canis had positive PCR test results.20 The authors of that study speculated that a negative PCR test result in a seropositive dog could be expected after immunologic or therapeutic cure or with low circulating numbers of organisms. In a similar study, 13 of 19 dogs at one institution and five of 19 dogs at another institution that were seroreactive by IFA had positive PCR test results.32

An advantage that PCR testing has over other modalities is the ability to identify the species causing infection, which is particularly helpful for pathogens for which there is extensive serologic cross-reactivity. Positive PCR results also add support to a diagnosis of an active infection by organisms such as Babesia or Borrelia species, to which dogs may be exposed and, thus, seropositive for but for which seroreactivity does not always equate to active infection. Detection of DNA for a specific tick-borne agent in a patient seropositive for the same organism supports a diagnosis of active infection when there are other supportive findings (e.g. from history, physical examination, other diagnostic tests). Another advantage of PCR testing is that it can be used to look for evidence of infection by one or more of a group of related organisms (e.g. Ehrlichia species) by using primers specific for the genus of interest. A PCR test result positive for Ehrlichia species could then suggest the need for additional PCR tests to identify the species present.

Limitations of PCR testing include limited availability, expense, inconsistent quality control, and lack of standardization among laboratories. Diagnostic PCR assays are improving with the implementation of real-time and nested PCR strategies and, as a result, are becoming more sensitive and specific.41,42

POTENTIAL INFLUENCE OF COINFECTION ON TREATMENT AND CLINICAL OUTCOME

Whenever possible, the goal when evaluating an ill patient is to make a diagnosis so that you can implement specific therapy. For patients with tick-transmitted diseases, failure to consider coinfection can lead to inappropriate and ineffective therapy, possibly prolonging the course of clinical illness. In the case cited earlier of the dog with bartonellosis and babesiosis,23 the dog's illness extended over five months until babesiosis was identified and treated.

Although many tick-borne infections are successfully treated with tetracycline and related antibiotics, this antimicrobial choice is not appropriate for all tick-transmitted diseases. While a clearly superior treatment protocol has not been established for Babesia canis infection, tetracyclines and imidocarb dipropionate are both effective.43 An optimal protocol for treating infection with Bartonella species has not been determined either but may include, in addition to tetracyclines, empirical treatment with antimicrobials such as enrofloxacin, azithromycin, and trimethroprim-sulfamethoxazole.5,44-49 Thus, patients with coinfections could require therapy with several different antimicrobials to effectively treat all pathogens.

Treatment and subsequent clinical recovery does not guarantee cure or immunity. It is important to note that dogs can become persistently infected or repeatedly reinfected with some of the tick-borne pathogens in endemic areas. Some dogs may have persistence of antibody titers after treatment, but the persistence of antibody reactivity after anti-rickettsial drug therapy does not necessarily equate with treatment failure. Dogs can have persistently elevated antibody titers for up to 36 months after treatment despite resolution of clinical signs and laboratory abnormalities.50 Hence antibody detection can be misleading in assessing treatment efficacy. PCR testing may help in assessing treatment efficacy because it may be able to differentiate between animals persistently infected and those that have persistent antibody titers despite successful treatment.1,51

CONCLUSION

Coinfection may account for some of the variations seen in clinical presentation, pathogenicity, and therapeutic response in patients with tick-borne infections. Evidence indicates that coinfections are found in some patients if an effort is made to identify them. Clinicians must use a combination of geography, clinical findings, and laboratory findings to help determine whether coinfection is present and decide which specific pathogens to test for. Knowing the advantages and limitations of each test can help clinicians efficiently use the arsenal of diagnostics available today. The use of molecular diagnostic assays such as PCR testing will help in documenting coinfections and contribute to a better understanding of the incidence of coinfections as well as our understanding of the clinical syndromes caused by coinfections.

Adam Mordecai, DVM
Erick Spencer, DVM
Rance K. Sellon, DVM, PhD, DACVIM
Department of Veterinary Clinical Sciences
College of Veterinary Medicine
Washington State University
Pullman, WA 99164-7060


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