Zoonotic bornavirus from variegated squirrel tied to fatal CNS infections in German breeders.
Three squirrel breeders in Germany likely died of a novel virus they caught from the animals, researchers said.
Over a 2-year period, the three men developed progressive encephalitis or meningoencephalitis that led to death within 2 to 4 months, according to Martin Beer, DVM, of the Friedrich-Loeffler-Institut in Greifswald-Insel Riems, Germany, and colleagues.
Genomic analysis found a previously unknown bornavirus in a contact squirrel and in brain tissue from the three men, the researchers reported, and it is the "likely causative agent" in their deaths.
The known bornavirus species infect a range of warm-blooded animals, from birds to primates, and are currently not thought to be responsible for human disease, Beer and colleagues noted.
But the new virus -- dubbed variegated squirrel 1 bornavirus (VSBV-1) -- is separate from the other species. "VSBV-1 is likely to be a previously unknown zoonotic pathogen transmitted by the variegated squirrel," they stated.
The investigation began in late 2011, when three men in succession (ages 63, 62, and 73, respectively) developed similar symptoms including fever, shivers, or both; progressive psychomotor slowing; confusion; unsteady gait, and myoclonus, ocular paresis, or both.
All three also developed bilateral crural-vein thrombosis, with a subsequent pulmonary embolism in two.
Finally, they lapsed into coma and died, Beer and colleagues reported, despite anti-infective chemotherapy.
The three men were friends, members of the same squirrel-breeding association, and often traded animals.
While they were alive, their cerebrospinal fluid showed pleocytosis, and MRI showed growing lesions in the cerebral cortical areas and basal ganglia or meninges.
While that finding is consistent with a viral infection, doctors were unable to find an infectious agent, despite detailed investigations of cerebrospinal fluid samples, biopsy samples, and serum, the researchers reported.
Analysis of the affected brain areas showed tissue swelling and necrosis, glial activation, and lymphocyte infiltration, but no viral inclusions or microorganisms, they said.
Beer and colleagues thought the squirrels might have played a role in the disease.
To investigate, they tested for a range of pathogens using a squirrel owned by the third patient, but when that screening came up negative they went on to analyze samples from the animal using metagenomic sequencing.
That analysis detected five RNA sequence fragments that were similar to a known bornavirus, Mammalian 1 bornavirus, in liver, lung, and kidney tissue and in chest-cavity fluid.
Using polymerase chain reaction methods, Beer and colleagues found similar RNA in other samples from the squirrel and in fresh-frozen brain tissue from all three patients.
Control tissues from patients with unrelated brain diseases and from healthy people did not contain any of the viral RNAs, they reported.
Deep sequencing of RNA from the squirrel and the third patient showed the two viral sequences were nearly identical and had a standard bornavirus genomic structure. Analysis showed the novel virus is a separate lineage from the known bornavirus species.
Finally, Beer and colleagues found that the third patient had antibodies to the virus in his serum and cerebrospinal fluid.
Taken together, the evidence isn't enough to prove that the novel virus caused the three deaths, Beer and colleagues concluded, but they argued it was highly suggestive of a novel zoonotic illness.
They added that the route of transmission from squirrels to patients "remains uncertain" although family members reported that two of the patients had been bitten or scratched.
They also noted that all three of the patients were older than 60 and had pre-existing medical conditions -- hypertension, diabetes, or obesity -- that might have "conferred a predisposition to clinical infection with this unusual agent."
It also remains unclear whether the virus was imported with the squirrels or whether it originated in mammals that were in contact with the breeding facilities, Beer and colleagues said.
Over a 2-year period, the three men developed progressive encephalitis or meningoencephalitis that led to death within 2 to 4 months, according to Martin Beer, DVM, of the Friedrich-Loeffler-Institut in Greifswald-Insel Riems, Germany, and colleagues.
Advertisement
The men, all from the German state of Saxony-Anhalt, bred variegated squirrels, a species native to Central and southern North America that is kept as an exotic pet in Europe, Beer and colleagues reported in the New England Journal of Medicine.Genomic analysis found a previously unknown bornavirus in a contact squirrel and in brain tissue from the three men, the researchers reported, and it is the "likely causative agent" in their deaths.
The known bornavirus species infect a range of warm-blooded animals, from birds to primates, and are currently not thought to be responsible for human disease, Beer and colleagues noted.
But the new virus -- dubbed variegated squirrel 1 bornavirus (VSBV-1) -- is separate from the other species. "VSBV-1 is likely to be a previously unknown zoonotic pathogen transmitted by the variegated squirrel," they stated.
The investigation began in late 2011, when three men in succession (ages 63, 62, and 73, respectively) developed similar symptoms including fever, shivers, or both; progressive psychomotor slowing; confusion; unsteady gait, and myoclonus, ocular paresis, or both.
Finally, they lapsed into coma and died, Beer and colleagues reported, despite anti-infective chemotherapy.
The three men were friends, members of the same squirrel-breeding association, and often traded animals.
While they were alive, their cerebrospinal fluid showed pleocytosis, and MRI showed growing lesions in the cerebral cortical areas and basal ganglia or meninges.
While that finding is consistent with a viral infection, doctors were unable to find an infectious agent, despite detailed investigations of cerebrospinal fluid samples, biopsy samples, and serum, the researchers reported.
Beer and colleagues thought the squirrels might have played a role in the disease.
To investigate, they tested for a range of pathogens using a squirrel owned by the third patient, but when that screening came up negative they went on to analyze samples from the animal using metagenomic sequencing.
That analysis detected five RNA sequence fragments that were similar to a known bornavirus, Mammalian 1 bornavirus, in liver, lung, and kidney tissue and in chest-cavity fluid.
Using polymerase chain reaction methods, Beer and colleagues found similar RNA in other samples from the squirrel and in fresh-frozen brain tissue from all three patients.
Deep sequencing of RNA from the squirrel and the third patient showed the two viral sequences were nearly identical and had a standard bornavirus genomic structure. Analysis showed the novel virus is a separate lineage from the known bornavirus species.
Finally, Beer and colleagues found that the third patient had antibodies to the virus in his serum and cerebrospinal fluid.
Taken together, the evidence isn't enough to prove that the novel virus caused the three deaths, Beer and colleagues concluded, but they argued it was highly suggestive of a novel zoonotic illness.
They added that the route of transmission from squirrels to patients "remains uncertain" although family members reported that two of the patients had been bitten or scratched.
It also remains unclear whether the virus was imported with the squirrels or whether it originated in mammals that were in contact with the breeding facilities, Beer and colleagues said.
Không có nhận xét nào:
Đăng nhận xét