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Fatal human rabies due to Duvenhage virus from a bat in Kenya: failure of treatment with coma-induction, ketamine, and antiviral drugs.

van Thiel PP, de Bie RM, Eftimov F, Tepaske R, Zaaijer HL, van Doornum GJ, Schutten M, Osterhaus AD, Majoie CB, Aronica E, Fehlner-Gardiner C, Wandeler AI, Kager PA - PLoS Negl Trop Dis (2009)

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. p.p.vanthiel@amc.uva.nl

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Rabies, encephalitis caused by lyssaviruses, was considered universally fatal until a young, unvaccinated patient with bat rabies survived after a new therapeutic approach... We report on a patient with rabies due to Duvenhage virus from a bat in Kenya... Treatment with intravenous immunoglobulin 0.4 g/kg/d for 5 days as for GBS and with acyclovir 10 mg/kg three times per day iv for 5 days as for herpes simplex encephalitis was started (PCR for herpes simplex virus and varicella zoster virus in serum and CSF proved negative)... Also, there was diffuse swelling of both hemispheres... Magnetic resonance angiography did not reveal vascular abnormalities... Brainstem reflexes and deep tendon reflexes were absent... Introduction of a tube to clean the airways did not result in a response of coughing and there was no spontaneous respiration... She died on day 20 of admission, 45 days after the incident with the bat... At postmortem examination no gross abnormalities were found, apart from the pneumonia... For the detection of the virus, polyclonal rabbit anti-rabies-nucleoprotein antibody (RNP; 1∶500, Centre of Expertise for Rabies, Ottawa, Canada) was used... This 15-year-old patient was diagnosed with encephalitis... She did not receive rabies immunoglobulin or rabies vaccine... It was suggested that infection by an attenuated variant bat rabies virus or early presence of rabies antibodies in serum and CSF could have contributed to the success ,,... As mentioned, this patient differs from the non-surviving patients because of the early administration of vaccine and presence of antibodies... Details and follow-up results are awaited.

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Histopathology rabies encephalitis due to Duvenhage virus.Rabies encephalitis (lyssavirus; genotype 4) brain pathology: cerebral cortex and anti-RNP Immunohistochemistry. (A) (HE staining): frontal cortex: extensive neuropil vacuolization and neuronal cell loss. (B) Few residual cortical neurons (arrows). (C) (HE staining): perivascular lymphocytic inflammatory infiltrates (arrows). (D and E) Anti-RNP immunoreactivity within the frontal cortex. Several neuronal cells show immunopositivity (arrows and insert in [E]) with multiple antigenic masses present in the neuronal cytoplasm, as well as in dendrites and axon. Scale bar: (A, B) 100 µm; (C, D) 60 µm; (E) 40 µm; insert in (E): 12 µm.
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pntd-0000428-g003: Histopathology rabies encephalitis due to Duvenhage virus.Rabies encephalitis (lyssavirus; genotype 4) brain pathology: cerebral cortex and anti-RNP Immunohistochemistry. (A) (HE staining): frontal cortex: extensive neuropil vacuolization and neuronal cell loss. (B) Few residual cortical neurons (arrows). (C) (HE staining): perivascular lymphocytic inflammatory infiltrates (arrows). (D and E) Anti-RNP immunoreactivity within the frontal cortex. Several neuronal cells show immunopositivity (arrows and insert in [E]) with multiple antigenic masses present in the neuronal cytoplasm, as well as in dendrites and axon. Scale bar: (A, B) 100 µm; (C, D) 60 µm; (E) 40 µm; insert in (E): 12 µm.

Mentions: At postmortem examination no gross abnormalities were found, apart from the pneumonia. The brain was swollen and weighed 1,360 g. Histopathology of the cerebral cortex (Figure 3A and 3B) showed extensive neuropil vacuolization, neuronal cell loss, astrogliosis, and widespread inflammatory changes consisting of macrophages, activated microglia, and lymphocytic infiltrates. Severe neuronal cell loss was observed in the hippocampus, midbrain, pons, medulla oblongata, and cerebellum. Immunohistochemistry using polyclonal rabbit anti-rabies nucleoprotein antibody showed rabies virus antigen in the frontal and temporal cortex, as well as in the hippocampus and entorhinal cortex (Figure 3C and 3D). Rabies virus antigen was not detected in other regions of the brain nor in adrenal glands, salivary gland, pancreas, thyroid, heart, or gastrointestinal tract.


Fatal human rabies due to Duvenhage virus from a bat in Kenya: failure of treatment with coma-induction, ketamine, and antiviral drugs.

van Thiel PP, de Bie RM, Eftimov F, Tepaske R, Zaaijer HL, van Doornum GJ, Schutten M, Osterhaus AD, Majoie CB, Aronica E, Fehlner-Gardiner C, Wandeler AI, Kager PA - PLoS Negl Trop Dis (2009)

Histopathology rabies encephalitis due to Duvenhage virus.Rabies encephalitis (lyssavirus; genotype 4) brain pathology: cerebral cortex and anti-RNP Immunohistochemistry. (A) (HE staining): frontal cortex: extensive neuropil vacuolization and neuronal cell loss. (B) Few residual cortical neurons (arrows). (C) (HE staining): perivascular lymphocytic inflammatory infiltrates (arrows). (D and E) Anti-RNP immunoreactivity within the frontal cortex. Several neuronal cells show immunopositivity (arrows and insert in [E]) with multiple antigenic masses present in the neuronal cytoplasm, as well as in dendrites and axon. Scale bar: (A, B) 100 µm; (C, D) 60 µm; (E) 40 µm; insert in (E): 12 µm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2710506&req=5

pntd-0000428-g003: Histopathology rabies encephalitis due to Duvenhage virus.Rabies encephalitis (lyssavirus; genotype 4) brain pathology: cerebral cortex and anti-RNP Immunohistochemistry. (A) (HE staining): frontal cortex: extensive neuropil vacuolization and neuronal cell loss. (B) Few residual cortical neurons (arrows). (C) (HE staining): perivascular lymphocytic inflammatory infiltrates (arrows). (D and E) Anti-RNP immunoreactivity within the frontal cortex. Several neuronal cells show immunopositivity (arrows and insert in [E]) with multiple antigenic masses present in the neuronal cytoplasm, as well as in dendrites and axon. Scale bar: (A, B) 100 µm; (C, D) 60 µm; (E) 40 µm; insert in (E): 12 µm.
Mentions: At postmortem examination no gross abnormalities were found, apart from the pneumonia. The brain was swollen and weighed 1,360 g. Histopathology of the cerebral cortex (Figure 3A and 3B) showed extensive neuropil vacuolization, neuronal cell loss, astrogliosis, and widespread inflammatory changes consisting of macrophages, activated microglia, and lymphocytic infiltrates. Severe neuronal cell loss was observed in the hippocampus, midbrain, pons, medulla oblongata, and cerebellum. Immunohistochemistry using polyclonal rabbit anti-rabies nucleoprotein antibody showed rabies virus antigen in the frontal and temporal cortex, as well as in the hippocampus and entorhinal cortex (Figure 3C and 3D). Rabies virus antigen was not detected in other regions of the brain nor in adrenal glands, salivary gland, pancreas, thyroid, heart, or gastrointestinal tract.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. p.p.vanthiel@amc.uva.nl

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Rabies, encephalitis caused by lyssaviruses, was considered universally fatal until a young, unvaccinated patient with bat rabies survived after a new therapeutic approach... We report on a patient with rabies due to Duvenhage virus from a bat in Kenya... Treatment with intravenous immunoglobulin 0.4 g/kg/d for 5 days as for GBS and with acyclovir 10 mg/kg three times per day iv for 5 days as for herpes simplex encephalitis was started (PCR for herpes simplex virus and varicella zoster virus in serum and CSF proved negative)... Also, there was diffuse swelling of both hemispheres... Magnetic resonance angiography did not reveal vascular abnormalities... Brainstem reflexes and deep tendon reflexes were absent... Introduction of a tube to clean the airways did not result in a response of coughing and there was no spontaneous respiration... She died on day 20 of admission, 45 days after the incident with the bat... At postmortem examination no gross abnormalities were found, apart from the pneumonia... For the detection of the virus, polyclonal rabbit anti-rabies-nucleoprotein antibody (RNP; 1∶500, Centre of Expertise for Rabies, Ottawa, Canada) was used... This 15-year-old patient was diagnosed with encephalitis... She did not receive rabies immunoglobulin or rabies vaccine... It was suggested that infection by an attenuated variant bat rabies virus or early presence of rabies antibodies in serum and CSF could have contributed to the success ,,... As mentioned, this patient differs from the non-surviving patients because of the early administration of vaccine and presence of antibodies... Details and follow-up results are awaited.

Show MeSH
Related in: MedlinePlus