Biomedical Engineering Reference
In-Depth Information
apparent that approximately 10% of transfused patients still
had posttransfusion hepatitis ( Alter et al., 1989 ). Ninety
percent of these cases were neither A nor B, so this human
disease was called non-A, non-B hepatitis (NANBH). It
was transmitted to chimpanzees ( Alter et al., 1978 ), which
have proved to be the only reliable animal model for
studying this disease ( Feinstone et al., 1981; Tabor et al.,
1983 ). After more than 10 years of research using chim-
panzees, in which infection is diagnosed by serum enzyme
elevation (ALT, GGT) and the presence of characteristic
electron microscopic ultrastructural changes in hepatocytes
and liver endothelial cells ( Pfeifer et al., 1980 ), the first
serological test for NANBH was produced from chim-
panzee plasma by genetic engineering ( Kuo et al., 1989 ).
The virus, then designated as hepatitis C virus (HCV), is
now known to be unique, but related to flaviviruses and
designated as hepacivirus ( Ashfaq et al., 2011 ). Conser-
vative scientists advise reserving the diagnosis of hepatitis
C infection for those cases of NANBH that are positive for
antibodies to HCV (anti-HCV) or are positive for HCV by
polymerase chain reaction (PCR).
agent has been isolated, classified as an enterovirus, and
experimentally transmitted to owl monkeys, cynomolgus
monkeys, and tamarins ( Krawczynski and Bradley, 1989;
Ticehurst et al., 1992 ), and a serological test is available. The
disease can be transmitted fromanimals to humans and can be
particularly severe in pregnant women ( Agarwal, 2011 ).
Prevention Although there are no reported cases of
spontaneously occurring HEV infection in monkeys, this is
a waterborne disease endemic in countries of origin,
especially of New World monkeys, so there is potential for
this disease to be brought in by newly imported animals.
The epidemiology is similar to that of hepatitis A, so
special emphasis on enteric precautions under Biosafety
Level 2 conditions is recommended because ISG does not
confer protection.
Callitrichid Hepatitis
In 198l, seven golden tamarins (Leontopithecus rosalia)
died at a zoo in the USA and 12 marmosets and tamarins
(family Callitrichidae) died at a zoo in England from an
acute, highly fatal, apparently infectious hepatitis of
unknown origin ( Phillips, 1981; Lucke and Bennett, 1982 ).
Soon thereafter, 12 more golden tamarins and 18 calli-
trichids representing five different species died in epizo-
otics of the same disease in zoos or animal parks in the
USA. The sporadic occurrence of epizootics in settings
where animals are usually displayed in small family groups
suggested that a reservoir species was involved in main-
taining and transmitting the virus.
Clinical signs and symptoms of callitrichid hepatitis
(CH) are nonspecific and include dyspnea, anorexia,
weakness, lethargy, and, frequently, prostration and death.
Postmortem findings include jaundice, nonsanguinous
pleural and pericardial effusions, subcutaneous and
intramuscular hemorrhages, and hepatospenomegaly.
Microscopic liver lesions include hepatocellular swelling
and necrosis with intracellular acidophilic inclusion
bodies (Councilman-like) and mild inflammatory cell
infiltration.
The virus isolated from these cases has been charac-
terized as an ultrastructurally typical arenavirus antigeni-
cally related to the Old World arenaviruses, which include
lymphocytic choriomeningitis virus (LCMV) ( Stephensen
et al., 1990 ). A close relationship between the CH virus and
LCMV is supported by the cross-reaction of several CH-
specific sera with LCMV-Armstrong, which was implicated
in several cases of asymptomatic LCMV infection in
a research colony of rhesus monkeys ( Armstrong and Lillie,
1934 ).
Prevention There is no evidence that chimpanzees have
naturally occurring NANBH, so only experimentally
infected animals pose a risk to handlers. The epidemiology
of NANBH is similar to that of hepatitis B, so Biosafety
Level 2 facilities and procedures are adequate.
Hepatitis D
Delta hepatitis is caused by a defective, incomplete DNA-
containing virus (HDV) that requires the presence of
a hepadnavirus antigen such as hepatitis B virus for repli-
cation. Therefore, this agent occurs only in hepadnavirus
carriers or individuals infected simultaneously with both
viruses. It has been studied in woodchucks with woodchuck
hepatitis virus (WHV) and in chimpanzees with HBV.
Prevention Animal Biosafety Level 2 is recommended.
Hepatitis B carrier chimpanzees and contact personnel
must be employed in such a way that there is no risk of
contaminating negative animals or contracting experimen-
tally induced HDV. There is no vaccine available for
hepatitis D; however, since disease occurs as a co-infection
or super-infection in persons with HBV, vaccination against
HBV also prevents HDV.
Hepatitis E
In the 1980s, a severe, often fatal, enterically transmitted form
of NANBH, designated as ET-NANBH to distinguish it from
the parenterally transmitted or post-transfusion PT-NANBH,
caused several large outbreaks in India, Nepal, Burma,
Pakistan, the Soviet Union, Africa, and Mexico ( Ve l a s q ue z
et al., 1990 ). Now known as the hepatitis E virus (HEV), this
Prevention Biosafety Level 2 practices, containment,
equipment, and facilities are recommended for all activities
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