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Diagnosing infectious disease
Using antibody titers to diagnose diseases can be helpful, but make sure you understand their limitations


Using titers to detect acute disease

Serum samples are often nonreactive for antibodies during the acute stages of infection. For example, when a tick transmits Rickettsia rickettsii, the organism responsible for Rocky Mountain spotted fever, to a dog, it takes time before there will be a significant antibody titer, Breitschwerdt says. Most dogs with Rocky Mountain spotted fever don't have circulating antibodies to the organism when a veterinarian first examines them for the illness. If you take a sample right when the signs start, the animal has not had time to mount an antibody response, and serum antibody titer results are likely to be nonreactive.

"The more pathogenic the infectious agent, the more rapid the antibody response occurs, and the higher the antibody titer to that organism as compared with other organisms," Breitschwerdt says. For example, dogs infected with R. rickettsii will seroconvert in a matter of days, going from undetectable organism-specific antibodies to titers that exceed 1:8192. In contrast, dogs infected with Borrelia burgdorferi, the bacterium that causes Lyme disease, may not seroconvert until four to six weeks after tick transmission of the bacteria, and peak titers can occur months later.

The problem is that many serious infections are not confirmed because owners have to bring the patients back to get another sample, which then has to be sent to the laboratory, all necessitating an additional expense. If the pet is getting better, the owner might not be that interested in knowing that the infection was truly Rocky Mountain spotted fever.

Whenever possible, however, it's important to confirm acute infection to know what was actually treated. Confirmation can also have public health implications for the owners and their families as well. Some diseases, such as Rock Mountain spotted fever and leptospirosis, can be transmitted to people. If a veterinarian confirms a dog was infected with Rocky Mountain spotted fever or leptospirosis, he or she is obligated to inform clients that they and their children could be at risk for infection, Breitschwerdt says.

With leptospirosis, the route of infection is by direct or indirect exposure to urine from an infected animal. If leptospirosis is diagnosed in a dog, it's important for you and your staff to take care in handling the dog's body fluids, especially its urine. Wearing gloves is essential whenever urine and soiled bedding are handled. You should consider goggles for eye protection as well.

Using titers to detect chronic diseases

Using serology to diagnose chronic disease is even more complicated. One reason is because some animals that have been infected for months or years do not have antibody titers. For example, dogs infected with Babesia or Leishmania species can be overtly healthy, PCR positive, but lack detectable antibodies to the respective organism. For this reason, many governments require both a negative serology and negative PCR test before an animal can be imported.

Lack of antibodies often occurs with bartonellosis. Research over the last two or three years has shown that half of dogs infected with Bartonella species don't have circulating antibodies. In addition, PCR testing is often not sensitive enough to detect infection with a Bartonella species unless the patient's blood sample is enriched in a specially developed liquid culture medium (Bartonella alpha Proteobacteria Growth Medium, or BAPGM) before performing the PCR test, Breitschwerdt says.

Another example of the limitations of using titers as a diagnostic tool involves cases of Leishmania species infections in dogs imported to the United States. Pets brought here by military families returning from bases in the Mediterranean represent the most common cases. Established several years ago as a standard of care, these dogs are now tested to see whether they have been exposed to Leishmania infantum by using antibody titers, but many dogs don't make antibodies for years after they have been exposed to the organism, making this type of screening ineffective. The same appears to be true with babeisosis and bartonellosis.

Breitschwerdt and others have spent years researching and trying to educate veterinarians about finding these diseases in animals when antibodies are not present. "This is unsettling for veterinarians because, historically, the only real diagnostic tool we had for many infectious diseases was testing for antibodies," Breitschwerdt says. "Now, to find DNA evidence of infection in a diseased animal without the animal's immune system responding to the organism is a relatively new concept."

Without a definitive diagnosis, chronically infected patients may not be getting the appropriate treatment. Removing infectious diseases from the differential diagnosis list based on antibody titer alone can be a mistake. "You can't always rule out some of those organisms based solely on a negative antibody titer," Breitschwerdt says.


Source: DVM360 MAGAZINE,
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