Mistaken rabies diagnosis could result from immune globulin effect

The presence of rabies antibodies in a patient should not necessarily result in a diagnosis of the disease if the patient has received immune globulin, according to researchers.

Intravenous immune globulin (IVIG) as treatment for rabies symptoms can contain those antibodies, masking the disease that is truly present, they wrote in an MMWR.

“These data suggest that detection of [Rabies lyssavirus neutralizing antibodies (RLNAs)] in serum of an unvaccinated patient is a reliable laboratory criterion for human rabies only if IVIG has not been administered shortly before serum collection,” Neil M. Vora, MD, of the CDC Office of Public Preparedness and Response, and colleagues wrote.

The researchers described 10 cases in which they said the confounding effect of IVIG was evident. Six patients had serum with RLNAs, despite not having been vaccinated, and met criteria for confirmed rabies because of symptoms consistent with the disease. Another four also had RLNAs despite not having been vaccinated.

Yet all the patients were eventually diagnosed with other diseases after it was found that IVIG treatment, and not rabies antigens, conferred the antibodies in each case. The first of the 10 cases was especially representative of the problem, the researchers said.

In that case, which occurred in 2013, a 28-year-old man with neither a history of rabies vaccination nor that of mammal exposure had fever, body aches, headache and neck stiffness. He was admitted to a hospital and soon experienced seizures.

RLNAs were not detected in serum collected from the patient 9 days after illness onset. However, they were detected in serum collected soon after IVIG was administered on days 21 and 22. The patient, whose treatment also included empiric antibiotics, was diagnosed with autoimmune encephalitis. His condition improved after treatment, the researchers said.

They added that, in that patient, “serum RLNA concentration decreased as time passed after IVIG administration, as would be expected if these serum RLNAs were the result of passive immunity through IVIG, rather than part of an active immune response to a natural Rabies lyssavirus infection.”

Vora and colleagues further suggested that RLNAs could have found their way to IVIG plasma because companies producing it also make rabies immune globulin, and plasma from people hyper immunized with rabies vaccine was used to create IVIG. People who donated IVIG plasma may also have been vaccinated for rabies, they added.

The researchers suggested that, in cases in which RLNAs are detected after IVIG treatment, testing the IVIG lot or lots used can help determine how likely rabies is the disease to treat. They also cautioned against relying on IVIG as an alternative treatment for rabies.

“It is important that IVIG not be used as a replacement for human rabies immune globulin when administering rabies postexposure prophylaxis,” they wrote. “Serum RLNA test results in patients who have not been vaccinated for rabies but who have recently received IVIG should be interpreted with caution when assessing whether a patient might have rabies.” – by Joe Green

Disclosures: Vora reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

The presence of rabies antibodies in a patient should not necessarily result in a diagnosis of the disease if the patient has received immune globulin, according to researchers.

Intravenous immune globulin (IVIG) as treatment for rabies symptoms can contain those antibodies, masking the disease that is truly present, they wrote in an MMWR.

“These data suggest that detection of [Rabies lyssavirus neutralizing antibodies (RLNAs)] in serum of an unvaccinated patient is a reliable laboratory criterion for human rabies only if IVIG has not been administered shortly before serum collection,” Neil M. Vora, MD, of the CDC Office of Public Preparedness and Response, and colleagues wrote.

The researchers described 10 cases in which they said the confounding effect of IVIG was evident. Six patients had serum with RLNAs, despite not having been vaccinated, and met criteria for confirmed rabies because of symptoms consistent with the disease. Another four also had RLNAs despite not having been vaccinated.

Yet all the patients were eventually diagnosed with other diseases after it was found that IVIG treatment, and not rabies antigens, conferred the antibodies in each case. The first of the 10 cases was especially representative of the problem, the researchers said.

In that case, which occurred in 2013, a 28-year-old man with neither a history of rabies vaccination nor that of mammal exposure had fever, body aches, headache and neck stiffness. He was admitted to a hospital and soon experienced seizures.

RLNAs were not detected in serum collected from the patient 9 days after illness onset. However, they were detected in serum collected soon after IVIG was administered on days 21 and 22. The patient, whose treatment also included empiric antibiotics, was diagnosed with autoimmune encephalitis. His condition improved after treatment, the researchers said.

They added that, in that patient, “serum RLNA concentration decreased as time passed after IVIG administration, as would be expected if these serum RLNAs were the result of passive immunity through IVIG, rather than part of an active immune response to a natural Rabies lyssavirus infection.”

Vora and colleagues further suggested that RLNAs could have found their way to IVIG plasma because companies producing it also make rabies immune globulin, and plasma from people hyper immunized with rabies vaccine was used to create IVIG. People who donated IVIG plasma may also have been vaccinated for rabies, they added.

The researchers suggested that, in cases in which RLNAs are detected after IVIG treatment, testing the IVIG lot or lots used can help determine how likely rabies is the disease to treat. They also cautioned against relying on IVIG as an alternative treatment for rabies.

“It is important that IVIG not be used as a replacement for human rabies immune globulin when administering rabies postexposure prophylaxis,” they wrote. “Serum RLNA test results in patients who have not been vaccinated for rabies but who have recently received IVIG should be interpreted with caution when assessing whether a patient might have rabies.” – by Joe Green

Disclosures: Vora reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.