From: Terry S. Singeltary Sr. (
Subject: Other Transmission Studies of CJD from Blood and Urine Into Mice...
Date: September 18, 2000 at 2:01 pm PST

In Reply to: Transmission of BSE by blood transfusion in sheep... posted by Terry S. Singeltary Sr. on September 15, 2000 at 9:29 am:

Transmission of Creutzfeldt-Jakob Disease from Blood and Urine Into Mice

The Lancet, November 9, 1985

Sir,--Professor Manuelidis and his colleagues (Oct 19, p896) report
transmission to animals of Creutzfeldt-Jakob disease (CJD) from the
buffy coat from two patients. We also transmitted the disease from
whole blood samples of a patient (and of mice) infected with CJD.1
Brain, Cornea, and urine from this patient were also infectious, and
the clinicopathological findings2 are summarised as follows.

A 70-year-old man was noted to have a slowing of speech and writing
and some disorientation, all of which progressed rapidly. Decorticate
rigidity, forced grasping, positive snout reflex, and myoclonus
appeared within 2 months. Electroencephalogram revealed typical
periodic synchronous discharge, and he died of pneumonia and upper
gastrointestinal haemorrhage, about 3 months after onset of the
symptoms. The Brain weighed 1290g and showed severe histological
changes diagnostic of CJD, including spongiform change, loss of
nerve cells, and diffuse proliferation of astrocytes. There were no
inflammatory cells, microglia, neurofibrillary tangles, and
amyloid plaques, although virus-like particles were detected by
electron microscopy.

Results of innoculation in Mice

Inocula NO* Incubation period (days)+
Brain 7/10 (4) 789 (+ or - 112)
Cornea 1/6 (0) 1037
Blood 2/13 (0) 1080 (+ or - 69)
Urine 5/10 (1) 880 (+ or - 55)
CSF 0/10

* Number of mice with CJD change/number examined histologically.
Number with amyloid plaques shown in parentheses.

+ means + or - SD

Samples were taken aseptically at necropsy. 10% crude homogenates
of brain and cornea in saline, whole blood (after crushing a clot),
and untreated CSF and urine were innoculated intracerebrally into
CF1 strain mice (20 ul per animal). Some mice showed emaciation,
bradykinesia, rigidity of the body and tail, and sometimes tremor
after long incubation periods. Tissues obtained after the animal
died (or was killed) were studied histologically (table). Animals
infected by various inocula showed common pathological changes,
consisting of severe spongiform changes, glial proliferation, and
a moderate loss of nerve cells. A few mice inoculated with brain
tissue or urine had the same amyloid plaques found in patients and
animals with CJD.3

In our long-term experiments, inoculating materials taken from
twenty patients with CJD or Gerstmann-Straussler-Scheinker's
disease (GSS) into rodents, positive results were obtained in
seventeen cases, including this patient. Brain tissue transmitted
the disease most frequently within the shortes incubation period,
except for one case where the lymph node was the most infectious.
Transmission through the cornea has been noted in man4 and in
guineapigs.5 Whole blood samples taken from three patients were
inoculated and a positive transmission occured only in the case
recorded here. Mouse-to-mouse transmission through blood
inoculation was successful after a mean incubation period of 365
days.1 Transmission through urine was positive in this patient
only, and negative in one other patient and in many infected animals.
Transmission through the CSF from eight patients was negative, yet
transmission via the CSF of infected rats was positive.1

As viraemia has been proved in guineapigs,6 mice,1,7 and lately
in patients with CJD, blood for transfusion or blood products for
medical use must be tested for unconventional pathogens. For this
purpose, we inoculated blood products inot rodents.8 The CJD
pathogen was not found in the products examined. However, this
approach takes too long to be of practical value. More efficient
methods must be developed to detect pathogens and to eliminate
them from blood. One proposal9 is to apply membrane filtration to
the pruification protocol of human growth hormone suspected of
being contaminated with CJD. Similar methods are needed for blood

Department of Neuropathology,
Neurological Institute,
Faculty of Medicine,
Kyushu University,
Fukuoka812, Japan


1. Tateishi J, Sato Y, Kaga M. Doi H, Ohta M. Experimental transmission
of human subacute spongiform encephalopathy to small
rodents 1: Clinical and histological observations.
Acta Neuropathol (Berl) 1980; 51: 127.

2. Shibayama Y, Sakaguchi Y, Nakata K, et al, Creutzfeldt-Jakob
disease with demonstration of virus-like particles.
Acta pathol Jpn 1982;32: 695.

3. Tateishi J, Nagara H, Hikita K, Sato Y. Amyloid plaques in the
brains of mice with Creutzfeldt-Jakob disease.
Ann Neurol 1984; 15: 278.

4. Duffy P, Wolf J, Colings G, DeVoe AG, Streeten B, Cowen D.
Possible person-to-person transmission of Creutzfeldt-Jakob disease.
N Engl J Med 1974; 290: 692.

5. Manuelidis EE, Angelo JN, Gorgacz EJ, Kim JH, Manuelidis L.
Experimental Creutzfeldt-Jakob disease transmitted via the eye
with infected cornea. N Engl J Med 1977; 296: 1334.

6. Manuelidis EE, Gorgacz EJ, Manuelidis L. Viremia in experimental
Creutzfeldt-Jakob disease. Science 1978: 200: 1069.

7. Kuroda Y, Gibbs CJ Jr, Amyx HL, Gajdusek DC.
Creutzfeldt-Jakob disease in mice. Persistent viremiam and
preferential replication of virus in low-density lymphocytes.
Infect Immun 1983; 41: 154.

8. Tateishi J, Tsuji S. Unconventional pathogens causing spongiform
encephalopathis absent in blood products. J Med Virol 1985; 15: 11.

9. Tateishi J, Kitamoto T, Hiratani H. Creutzfeldt-Jakob disease
pathogen in growth hormone preparations is eliminatable.
Lancet (in press).

also, this from the Her Majesty's Government...TSS

Subject: Transmission of TSEs through blood
Date: Tue, 28 Mar 2000 14:48:35 +0100
From: Ralph Lucas
Reply-To: Bovine Spongiform Encephalopathy

######### Bovine Spongiform Encephalopathy #########

The Lord Lucas asked Her Majesty's Government:

Whether there is any evidence that any Transmissible Spongiform
Encephalopathy in any species can be transmitted through blood; and whether they will place in the Library of the House copies of the principal relevant scientific papers. (HL1545)

The Parliamentary Under-Secretary of State, Department of Health (Lord Hunt of Kings Heath):

Some animal studies have shown that certain transmissible spongiform
encephalopathies can be experimentally transmitted from animal to animal through blood components. However, the Spongiform Encephalopathy Advisory Committee at its February meeting reviewed recent research undertaken in this area and did not consider any measures were necessary, in addition to those already in place, to reduce any potential risk to public health from human blood and blood products.

Copies of the following relevant scientific papers are being placed in the Library.

Brown P, 1995, "Can Creutzfeldt-Jakob Disease be transmitted by
Transfusion?" Haematology 2: 472 - 477.

Brown et al 1999, Further studies of blood infectivity in an experimental model of transmissible spongiform encephalopathy, with an explanation of why blood components do not transmit Creutzfeldt - Jakob disease in humans.

Transfusion Vol. 39, November/December 1169 - 1178.