Treatment of porcine cysticercosis with oxfendazole: A dose-response trial

Article (PDF Available)inThe Veterinary record 141(16):420-2 · November 1997with 307 Reads
DOI: 10.1136/vr.141.16.420 · Source: PubMed
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Abstract
Taenia solium cysticercosis is an important public health problem in developing countries. Oxfendazole has been shown to be highly effective against porcine cysticercosis, when given as a single dose at 30 mg/kg bodyweight. This dose, however, was estimated from experience with albendazole. A controlled dose-response trial was therefore undertaken to determine the efficacy and safety of three concentrations of oxfendazole. Twenty-four naturally parasitised pigs were divided into four groups and treated with oxfendazole at 10 mg/kg, 20 mg/kg or 30 mg/kg, or left untreated. Eight to 10 weeks later the pigs were killed and the viability of the parasites assessed by evagination. No side-effects of oxfendazole treatment were observed. In the control group more than 90 per cent of the cysts were viable. Viable cysts were found in the muscle and brain of the pigs treated with 10 or 20 mg/kg oxfendazole. At 30 mg/kg there were no viable cysts in any of the tissues examined, indicating that this concentration of oxfendazole provided an effective treatment against porcine cysticercosis.
The
Veterinary
Record,
October
18,
1997
Treatment
of
porcine
cysticercosis
with
oxfendazole:
a
dose-response
trial
A.
E.
Gonzalez,
N.
Falcon,
C.
Gavidia,
H.
H.
Garcia,
V.
C.
W.
Tsang,
T.
Bemal,
M.
Romero,
R.
H.
Gilman
Veterinary
Record
(1997)
141,
420-422
Taenia
solium
cysticercosis
is
an
important
public
health
problem
in
developing
countries.
Oxfendazole
has
been
shown
to
be
highly
effective
against
porcine
cysticercosis,
when
given
as
a
single
dose
at
30
mg/kg
bodyweight.
This
dose,
however,
was
estimated
from
experience
with
albendazole.
A
controlled
dose-response
trial
was
therefore
undertaken
to
determine
the
efficacy
and
safety
of
three
concentrations
of
oxfendazole.
Twenty-four
naturally
parasitised
pigs
were
divided
into
four
groups
and
treated
with
oxfendazole
at
10
mg/kg,
20
mg/kg
or
30
mg/kg,
or
left
untreated.
Eight
to
10
weeks
later
the
pigs
were
killed
and
the
viability
of
the
parasites
assessed
by
evagination.
No
side-effects
of
oxfendazole
treatment
were
observed.
In
the
control
group
more
than
90
per
cent
of
the
cysts
were
viable.
Viable
cysts
were
found
in
the
muscle
and
brain
of
the
pigs
treated
with
10
or
20
mg/kg
oxfendazole.
At
30
mg/kg
there
were
no
viable
cysts
in
any
of
the
tissues
exam-
ined,
indicating
that
this
concentration
of
oxfendazole
provid-
ed
an
effective
treatment
against
porcine
cysticercosis.
Taenia
solium
cysticercosis
is
a
common
disease
in
pig-
rearing
areas
of
developing
countries
(Acha
and
Szyfres
1986).
The
life
cycle
of
this
cestode
includes
the
pig,
as
the
normal
intermedi-
ate
host
harbouring
the
larval
form
or
cysticercus,
and
man,
as
the
definitive
host
harbouring
the
adult
form
of
the
tapeworm.
Humans
can
also
serve
as
the
intermediate
host
and
develop
the
cystic
form
by
the
accidental
ingestion
of
tapeworm
eggs
(Nash
and
Neva
1984).
T
solium
is
responsible
for
more
than
10
per
cent
of
acute-
care
admissions
of
people
to
neurological
wards
in
some
countries
(Garcia
and
others
1991),
and
nearly
30
per
cent
of
late-onset
seizures
in
people
living
in
endemic
zones
are
associated
with
sero-
logical
evidence
of
infection
(Garcia
and
others
1993).
The
rates
of
porcine
infection
are
variable,
but
in
endemic
regions
more
than
50
per
cent
of
pigs
may
be
infected
(Gonzalez
and
others
1990),
pro-
ducing
widespread
livestock
production
losses
(Murrel
1991).
In
Mexico,
porcine
cysticercosis
is
estimated
to
be
responsible
for
the
loss
of
more
than
a
half
of
the
national
investment
in
pig
production
and
to
cost
more
than
US$
20
million
annually
in
hospitalisation
and
treatment
costs
for
people
with
cysticercosis
(Murrel
1991).
Oxfendazole
(5-[phenylsulphinyl]-lH-benzimidazole-2-yl
car-
bamic
acid
methyl
ester)
was
first
shown
to
have
anthelmintic
properties
against
larval
and
adult
forms
of
gastrointestinal
ces-
todes
and
nematodes
in
various
animal
species
in
the
laboratories
of
Syntex
Research,
Palo
Alto,
California.
Oxfendazole,
adminis-
tered
as
a
single
dose
of
30
mg/kg
bodyweight,
is
highly
effective
for
the
treatment
of
porcine
cysticercosis
(Gonzalez
and
others
1996).
However,
this
dose
was
based
upon
previous
experiences
with
albendazole
and
may
overestimate
the
amount
of
drug
need-
ed
to
treat
cysticercosis.
This
experiment
was
designed
to
deter-
mine
the
minimal
effective
single
dose
of
oxfendazole
required
to
kill
all
cysticercotic
cysts
in
pigs.
A.
E.
Gonzalez,
DVM,
MMic,
N.
Falcon,
DVM,
C.
Gavidia,
DVM,
T.
Bernal,
DVM,
M.
Romero,
DVM,
Facultad
de
Medicina
Veterinaria,
Universidad
Mayor
de
San
Marcos,
Lima,
Peru
H.
H.
Garcia,
MD,
R.
H.
Gilman,
MD,
DTMH,
Departamentos
de
Microbiologia
y
Patologia,
Universidad
Peruana
Cayetano
Heredia,
Lima,
Peru
V.
C.
W.
Tsang,
PhD,
Parasitic
Diseases
Branch,
Centers
for
Disease
Control,
Atlanta,
Georgia,
USA
Materials
and
methods
Animals
Twenty-four
privately
reared
pigs
sold
for
slaughter
were
pur-
chased
at
Huancayo,
a
city
in
the
Peruvian
Sierra
and
taken
to
the
veterinary
facilities
in
Lima.
These
facilities
are
free
from
any
risk
of
the
transmission
of
cysticercosis.
All
the
pigs
had
palpable
lin-
gual
nodules,
implying
a
heavy
cysticercosis
infection.
Each
pig
was
weighed
and
given
swine
cholera
vaccine
immediately
after
purchase.
The
pigs
were
fed
ad
libitum
with
a
commercial
farm
diet
and
no
other
medication
was
given.
The
pigs
were
divided
into
four
similar
groups
of
six,
based
on
their
liveweights
and
estimated
burdens
of
infection
(assessed
grossly
by
an
examination
of
their
tongues).
These
groups
were
randomly
assigned
to
treatment
with
oxfendazole,
at
either
10,
20
or
30
mg/kg
bodyweight,
or
to
no
treatment
(controls).
The
30
mg/kg
group
was
later
reduced
to
five
animals
because
one
of
the
pigs
in
the
group
died
before
treatment
began.
All
the
pigs
were
coded
and
labelled,
and
each
group
was
housed
in
a
single
pen.
Oxfendazole
was
given
orally,
mixed
with
the
food.
The
therapeu-
tic
schedule
was
not
disclosed
to
the
personnel
who
conducted
the
necropsies
and/or
evagination
tests.
Serology
Enzyme-linked
immunoelectrotransfer
blot
(EITB)
assays
were
carried
out
as
described
by
Tsang
and
other
(1989,
1991).
In
brief,
this
assay
utilises
seven
purified
T
solium
glycoprotein
antigens
(diagnostic
bands
GP50,
GP42-39,
GP24,
GP21,
GP18,
GP14
and
GP13)
in
an
immunoblot
format
to
detect
infection-specific
antibodies
in
pigs
(Gonzalez
and
others
1990,
Tsang
and
others
1991).
Reactions
to
at
least
one
band
are
considered
positive.
Necropsy
and
cyst
collection
The
pigs
were
killed
eight
to
10
weeks
after
being
treated
with
oxfendazole.
A
postmortem
examination
was
carried
out
on
each
carcase,
during
which
the
psoas
and
anconeal
muscles,
the
tongue,
the
heart,
and
the
brain
of
each
pig
were
dissected.
All
the
cysts
(up
to
25)
present
in
the
left
psoas
and
anconeal
muscles,
and
in
the
left
half
of
the
tongue,
heart
and
brain,
were
removed
and
test-
ed
for
viability
by
evagination.
If
more
than
25
cysts
were
present
in
a
sample,
evagination
was
tested
in
only
25,
with
the
exception
of
two
samples
of
muscle
and
one
of
tongue
in
which
27,
58
and
28
cysticerci
were
tested.
Evagination
The
excised
cysts
were
evaginated
as
follows:
they
were
washed
in
sterile
phosphate
buffered
saline
(PBS,
0.
15M;
pH
7-2)
and
incu-
bated
in
bovine
bile
for
two
hours
at
37°C.
The
criterion
used
to
define
a
positive
evagination
was
the
presence
of
a
moving
scolex
outside
the
bladder
wall.
The
number
and
proportion
of
cysts
which
evaginated
were
recorded
for
each
location
in
each
pig.
Data
analysis
Differences
between
the
groups
were
tested
using
a
non-
420
group.bmj.com on March 16, 2013 - Published by veterinaryrecord.bmj.comDownloaded from
The
Veterinary
Record,
October
18,
1997
TABLE
1:
Mean
evagination
(%)
of
cysticerci
in
each
tissue
from
oxfendazole-treated
and
untreated
control
pigs,
according
to
dose
Dose
Muscle
Heart
Tongue
Brain
(mg/kg)
(%)
(%)
(%)
(%)
0
90-7
99-2
100.0
75-2
10
1,)0
0
4-0
4-5
20
5-0
0
0
12-3
30
0
0
0
0
parametric
one-way
analysis
of
variance
(Kruskall-Wallis)
with
spss
Statistical
Software.
Results
All
the
pigs
were
found
to
be
seropositive
by
EITB.
After
treat-
ment,
they
all
had
normal
feeding
habits,
activities
and
behaviour,
and
no
side-effects
were
observed.
More
than
75
per
cent
of
the
cysts
in
the
pigs
from
the
control
group
were
viable,
irrespective
of
their
anatomical
location.
There
were
viable
parasites
in
sam-
ples
from
four
of
the
pigs
in
the
10
mg/kg
group;
in
the
muscle
of
three
pigs,
the
tongue
of
two
pigs,
and
the
brain
of
two
pigs.
There
were
also
viable
cysts
in
samples
from
four
of
the
pigs
in
the
20
mg/kg
group;
in
the
muscle
of
one
pig
and
the
brain
of
three
pigs
(Table
1).
The
proportion
of
viable
cysts
in
the
pigs
from
these
groups
was
very
low:
18
out
of
216
(8
per
cent)
at
10
mg/kg,
and
11
out
of
198
(6
per
cent)
at
20
mg/kg.
No
viable
cysts
were
recovered
from
the
pigs
treated
with
30
mg/kg
oxfendazole.
There
was
a
significant
difference
between
the
treat-
ed
and
control
pigs
(P<0-001).
The
proportion
of
cysts
that
evagi-
nated,
and
were
therefore
presumed
to
be
viable
and
infective,
from
each
tissue
is
shown
in
Table
2.
Most
of
the
cysts
recovered
showed
marked
signs
of
degeneration
or
remained
as
minuscule
scars.
The
carcases
of
the
pigs
treated
with
30
mg/kg
had
a
nor-
mal
appearance
and
would
have
been
considered
suitable
for
human
consumption.
Discussion
The
results
of
this
study
confirm
the
safety
and
efficacy
of
a
single
dose
of
30
mg/kg
oxfendazole
for
the
treatment
of
porcine
cysticercosis.
This
was
the
minimal
effective
dose,
that
is,
the
dose
that
killed
all
the
parasites
with
no
detectable
side-effects
and
left
the
meat
fit
for
human
consumption.
Although
several
drugs
have
been
tested
for
the
treatment
of
porcine
cysticercosis,
oxfendazole
is
the
only
effective,
single
dose
therapy
(Gonzalez
and
others
1996).
Early
studies
with
flubendazole
(Tellez-Giron
and
others
1981)
were
followed
by
tests
of
different
dosages
of
praziquantel
in
15-day
therapies
(Flisser
and
others
1990)
with
variable
efficacy.
A
single
dose
of
praziquantel
was
later
reported
to
kill
all
the
cysts
in
10
of
17
pigs
(59
per
cent)
(Torres
and
others
1992).
The
authors
have
shown
that
albendazole
is
an
effective
drug
for
porcine
cysticercosis,
but
it
has
three
major
drawbacks:
first,
that
multiple-dose
schedules
are
required;
secondly,
that
it
has
severe
side-effects;
and
thirdly,
that
the
cysts
are
not
completely
reabsorbed
(Gonzalez
and
others
1995).
An
effective
therapy
for
porcine
cysticercosis
will
interrupt
the
life
cycle
of
T
solium
and
improve
control
programmes
for
cysti-
cercosis.
At
present
the
control
of
porcine
cysticercosis
is
based
primarily
on
the
inspection
and
condemnation
of
infected
carcases
(Gemmell
and
others
1983).
Fewer
than
10
per
cent
of
pigs
in
Peru
are
registered,
however,
and
55
per
cent
are
slaughtered
illegally
(Cysticercosis
Working
Group
in
Peru
1993).
As
a
result
control
measures
to
prevent
human
consumption
of
the
meat
are
impractical
and
inadequate
in
endemic
areas.
In
slaughterhouses
at
which
carcases
are
not
controlled
and
contiscated
the
rates
of
infection
among
pigs
may
be
as
high
as
30
per
cent
(Cysticercosis
Working
Group
in
Peru
1993).
A
series
of
specific
control
mea-
sures,
other
than
just
abattoir
inspection,
has
been
advocated
to
TABLE
2:
Evagination
(%)
of
cysts
from
the
four
tissues
taken
from
each
animal
in
the
three
treated
groups
and
the
control
group
Dose
Muscle
Heart
Tongue
Brain
(mg/kg)
(%)
(%)
(%)
(%)
0
100
(25/25)-
100
(25/25)
100
(25/25)
38
(3/8)
0
60
(14/25)
95
(21/22)
100
(25/25)
84
(21/25)
0
100
(25/25)
100
(24/24)
100
(24/24)
100
(25/25)
0
96
(24/25)
100
(25/25)
100
(25/25)
92
(23/25)
0
88
(22/25)
100
(25/25)
100
(25/25)
60
(15/25)
0
100
(25/25)
100
(19/19)
100
(25/25)
77
(10/13)
10
14
(3/21)
0
(0/1)
0
(0/28)
0
(0/2)
10
21
(3/14)
0(0/0)
9(1/11)
0(0/1)
10
0
(0/6)
0
(0/2)
0
(0/0)
0
(0/6)
10
25
(4/16)
0
(0/15)
15
(3/20)
17
(3/18)
10
0
(0/5)
0
(0/1)
0
(0/0)
0
(0/2)
10
0
(0/25)
0
(0/5)
0
(0/7)
10
(1/10)
20
0
(0/17)
0
(0/18)
0
(0/0)
8
(1/13)
20
0
(0/18)
0
(0/9)
0
(0/0)
0
(0/0)
20
0
(0/11)
0
(0/7)
0
(0/0)
33
(1/3)
20
30
(8/27)
0
(0/6)
0
(0/22)
0
(0/0)
20
0
(0/3)
0
(0/8)
0
(0/0)
0
(0/0)
20
0
(0/24)
0
(0/9)
0
(0/0)
33
(1/3)
30
0
(0/58)
0
(0/0)
0
(0/0)
0
(0/9)
30
0
(0/8)
0
(0/5)
0
(0/0)
0
(0/3)
30
0
(0/7)
0
(0/3)
0
(0/0)
0
(0/1)
30
0
(0/8)
0
(0/0)
0
(0/0)
0
(0/2)
30
0
(0/19)
0
(0/7)
0
(0/0)
0
(0/0)
Number
evaginated/number
examined
avoid
human
and
porcine
cysticercosis,
including
community
health
education
(Schantz
and
others
1993),
and
massive
human
chemotherapy
(Pawlowski
1987,
Cruz
and
others
1989,
Diaz
and
others
1991),
but
no
sustainable
control
has
yet
been
achieved.
People
can
only
become
infected
with
the
adult
stage
of
this
parasite
when
they
ingest
contaminated
pork.
The
treatment
of
pigs
before
they
are
slaughtered
may
block
a
key
step
in
the
trans-
mission
cycle
of
cysticercosis.
Better
market
prices
for
treated
pork
and
access
to
the
formal
marketing
system
would
be
strong
incentives
for
farmers
to
treat
their
pigs,
and
community
coopera-
tion
should
be
ensured.
Furthermore,
the
actual
cost
of
treating
an
adult
pig
with
oxfendazole
is
less
than
US$
1.50,
opening
the
pos-
sibility
for
self-sustaining,
community-managed
programmes.
Until
a
vaccine
for
porcine
cysticercosis
becomes
available,
the
treatment
of
infected
pigs
with
oxfendazole
is
a
logical
approach
for
controlling
the
disease,
and
should
therefore
be
considered
an
important,
cost-effective
addition
to
the
control
of
cysticercosis.
Acknowledgements.
-
This
study
was
funded
in
part
by
grants
from
the
Fundacion
Hipolito
Unanue,
and
CONCYTEC,
Lima,
Peru,
and
by
the
Intemational
Foundation
for
Science,
Syntex
Animal
Health,
and
grant
number
1-UOI
A135894-01
from
the
National
Institutes
for
Health.
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Short
Communications
Persistent
activity
of
injectable
ivermectin
against
important
gastrointestinal
nematodes
of
sheep
W.
T.
R.
Grimshaw,
C.
Hong,
K.
R.
Hunt
Veterinary
Record
(1997)
141,
422-424
THE
persistent
activity
of
ivermectin
administered
by
subcuta-
neous
injection
in
cattle
is
widely
recognised
(Barth
1983,
Bremner
and
others
1983,
Armour
and
others
1985,
Yazwinski
and
others
1993).
In
contrast,
very
few
reports
have
been
pub-
lished
on
the
persistent
activity
of
injectable
ivermectin
against
gastrointestinal
nematodes
in
sheep.
There
are
probably
two
major
reasons
for
this
situation.
First,
oral
formulations
tend
to
be
pre-
ferred
by
sheep
farmers,
particularly
for
use
in
lambs,
and
the
oral
formulation
of
ivermectin
is
highly
effective
against
all
the
impor-
tant
gastrointestinal
nematodes
of
sheep.
Secondly,
the
injectable
formulation
of
ivermectin
has
mainly
been
used
for
the
treatment
and
control
of
psoroptic
mange
(sheep
scab),
with
the
nematocidal
efficacy
merely
being
regarded
as
an
added
bonus.
The
potential
for
the
use
of
injectable
ivermectin
for
nematode
control,
particularly
in
ewes,
has
been
recognised
(McKellar
and
others
1988)
but,
in
the
absence
of
detailed
information
regarding
its
persistent
effects
on
the
important
gastrointestinal
nematode
species,
rational
strategies
cannot
be
formulated.
The
data
current-
ly
available
are
contradictory.
McKenna
(1986)
was
unable
to
show
any
persistent
effect
against
Ostertagia
circumcincta,
Haemonchus
contortus
and
Trichostrongylus
species
but
could
show
some
persistence
against
Cooperia
curticei.
In
contrast,
Borgsteede
(1993)
demonstrated
persistent
effects
against
H
con-
tortus,
Trichostrongylus
vitrinus
and
C
curticei.
The
current
study
was
designed
to
evaluate
the
persistent
activity
of
injectable
iver-
mectin
against
the
important
gastrointestinal
nematodes
in
sheep
in
the
UK,
particularly
0
circumcincta,
for
which
no
persistent
effect
has
been
demonstrated.
Fourteen
female
and
10
male
neutered,
parasite-naive
Dorset
Horn
lambs,
which
were
born
in
April
1992
and
raised
at
the
Central
Veterinary
Laboratory
(Weybridge)
under
conditions
pre-
cluding
helminth
infections,
were
used.
The
lambs
were
approxi-
mately
seven
months
old
at
the
start
of
the
trial,
and
weighed
from
24
to
54
kg,
(females
24
to
43
kg,
males
28
to
54
kg).
The
lambs
were
randomly
allocated
to
treatment
groups
by
bodyweight
only.
The
lambs
were
housed
in
a
covered
building
where
they
were
randomly
distributed
into
three
pens
with
tiled
floors
covered
in
wood
shavings
which
were
replaced
daily.
They
were
fed
a
com-
mercially
available
concentrated
lamb
creep
feed
and
hay
and
water
ad
libitum.
On
day
0
(November
6,
1992)
the
lambs
were
weighed
and
ranked
according
to
bodyweight.
The
ranking
was
then
divided
into
six
groups
of
four
lambs.
Within
each
group
one
animal
was
randomly
allocated
to
each
of
four
treatment
groups
designated
groups
1
to
4.
Ivermectin
1
per
cent
w/v
injectable
solution
(Ivomec
Injection
for
Sheep;
MSD
AgVet)
was
administered
by
subcutaneous
injection
at
a
dose
rate
of
approximately
200
pg/kg
according
to
the
manufacturer's
recommendations.
Lambs
of
less
than
25
kg
bodyweight
received
0-5
ml
injectable
ivermectin,
those
between
25
and
50
kg
bodyweight
received
1
ml
and
those
between
51
and
75
kg
bodyweight
received
1-5
ml.
The
lambs
in
group
1
were
treated
on
day
0,
those
in
group
2
on
day
3
and
those
in
group
3
on
day
6.
The
six
lambs
in
group
4
were
kept
as
untreated
controls.
Ten
days
after
the
experiment
began,
all
the
lambs
in
each
of
the
four
groups
were
given
an
oral
infection
of
5000
0
circum-
cincta
L3,
5000
H
contortus
L3
and
7500
T
colubriformis
L3.
All
three
nematode
species
were
benzimidazole-resistant
strains
which
were
maintained
as
monocultures
at
the
Central
Veterinary
Laboratory.
The
timing
of
treatment
and
challenge
in
the
three
treatment
groups
allowed
assessment
of
the
persistent
activity
of
injectable
ivermectin
at
four,
seven
and
10
days
after
treatment.
Faecal
egg
counts
were
performed
on
faecal
samples
taken
before
treatment
and
34
days
after
treatment.
Nematode
eggs
were
counted
before
treatment
by
the
centrifugal
flotation
technique
and
by
a
modified
McMaster
technique
(MAFF
1986)
34
days
later.
The
lambs
were
slaughtered
on
day
34
and
worm
burdens
recovered
and
counted
by
standard
techniques
(MAFF
1986).
Geometric
means
were
calculated
for
faecal
egg
counts
and
burdens
of
each
parasite
species
using
the
transformation
to
the
natural
logarithm
W.
T.
R.
Grimshaw,
BVMS,
PhD,
MRCVS,
MSD
AgVet,
Hertford
Road,
Hoddesdon,
Hertfordshire
EN
1I
9BU
C.
Hong,
BSc,
PhD,
K.
R.
Hunt,
HNC,
Department
of
Parasitology,
Central
Veterinary
Laboratory
(Weybridge),
New
Haw,
Surrey
KT15
3NB
Dr
Grimshaw
died
in
1996,
Dr
Hong
died
in
1995
422
group.bmj.com on March 16, 2013 - Published by veterinaryrecord.bmj.comDownloaded from
doi: 10.1136/vr.141.16.420
1997 141: 420-422Veterinary Record
A. E. Gonzalez, N. Falcon, C. Gavidia, et al.
oxfendazole: a dose-response trial
Treatment of porcine cysticercosis with
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  • Article
    Full-text available
    Background The application of effective vaccines against pig cysticercosis and mass chemotherapy against pig cysticercosis and human taeniasis have shown the feasibility of interrupting the parasite’s life cycle in endemic areas. Methods A mathematical model that divides the population into susceptible, infected, and vaccinated individuals is formulated. The model is based upon the life cycle of the parasite. Computer numerical simulation experiments to evaluate the impact of pig vaccination under different vaccination schedules, and combined intervention strategies including pig vaccination and anthelmintic treatment against human taeniasis are carried out. Results Vaccination against either pig cysticercosis or against human taeniasis will influence the transmission dynamics not only among vaccinees but also the dynamics of the other hosts as well. When the protective efficacy and/or the coverage rate is less than 100%, different mass interventions like vaccinating the pig population twice in combination with chemotherapeutic treatment against human taeniasis, the elimination of the infection in both pigs and humans can also be achieved. Conclusions Our mathematical model has the potential for planning, and designing effective intervention strategies including both mass vaccination and/or chemotherapeutic treatment to eliminate pig cysticercosis, human taeniasis and human neurocysticercosis. The model can be adapted to any given community with mild, moderate endemicity, or even in hyperendemic regions. Electronic supplementary material The online version of this article (10.1186/s12976-019-0100-x) contains supplementary material, which is available to authorized users.
  • Article
    Full-text available
    Background Taenia solium is the aetiological agent of human taeniasis, pig cysticercosis and human neurocysticercosis, which are serious public health problems, especially in developing countries. Methods A mathematical model of the transmission dynamics of taeniasis-cysticercosis is formulated. The model consists of a coupled system of differential equations, which are density-dependent equations for describing the flow of the parasite through the life cycle. The model is hybrid since it comprises deterministic equations with stochastic elements which describe changes in the mean parasite burden and incorporates the overall pattern of the parasites’ distribution. Results Sensitivity and bifurcation analyses were carried out to determine the range of values of the model. The model can reproduce the observed epidemiological patterns of human taeniasis, pig and human cysticercosis. For example, for a wide range of parameter values, the mean intensity of adult worms tends to rapidly stabilize in one parasite per individual host. From this model, we also derived a Susceptible-Infected model to describe the prevalence of infection in humans and pigs. Chemotherapeutic interventions against pig cysticercosis or human taeniasis may reduce rapidly and effectively the mean intensity of human taeniasis, pig cysticercosis and human cysticercosis. This effect can be achieved even if the protective efficacy of the drug is of the order of 90% and the coverage rate is 90%. This means that health in humans infected either with adult worms or cysticerci may be achieved by the application of anthelmintic drugs against pig cysticercosis. However, treatment against human cysticercosis alone, does not influence neither human teniasis nor pig cysticercosis. This is because human cysticercosis infection does not influence the value of the basic reproductive number (Ro). Conclusions Even coverage of 100% in the administration of anthelmintics did not eliminate the infection. Then elimination of the infection in all hosts does not seem a feasible goal to achieve by administering only chemotherapeutic interventions. Throughout the manuscript a discussion of our model in the context of other models of taeniasis-cysticercosis is presented. Electronic supplementary material The online version of this article (10.1186/s12976-018-0090-0) contains supplementary material, which is available to authorized users.
  • Article
    Full-text available
    Neurocysticercosis is a nervous system infection caused by the larvae (cysticercus) of the pork tapeworm (Taenia solium). Neurocysticercosis is the primary cause of acquired epilepsy worldwide and, therefore, a global public health problem. On the other hand, T. solium taeniasis/cysticercosis is one of very few infectious diseases considered to be potentially eradicable. Recently, a large-scale elimination program in Tumbes, Peru, demonstrated the feasibility of interrupting transmission. Based on these advances, a series of initial guidelines are proposed aimed at setting out the foundations for regional and national taeniasis/cysticercosis control programs, with simple and feasible local interventions as a starting point.
  • Chapter
    Full-text available
  • Article
    Cysticercosis is a parasitic disease that frequently involves the human central nervous system (CNS) and current treatment options are limited. Oxfendazole, a veterinary medicine belonging to the benzimidazole family of anthelmintic drugs, has demonstrated substantial activity against the tissue stages of Taenia solium and has potential to be developed as an effective therapy for neurocysticercosis. To accelerate the transition of oxfendazole from veterinary to human use, the pharmacokinetics, safety and tolerability of oxfendazole were evaluated in healthy volunteers in this Phase 1 first-in-human (FIH) study. Seventy subjects were randomly assigned to receive a single oral dose of oxfendazole (0.5, 1, 3, 7.5, 15, 30 or 60 mg/kg) or placebo and were followed for 14 days. Blood and urine samples were collected and the concentrations of oxfendazole were measured using a validated ultra-performance liquid chromatography mass spectrometry method. The pharmacokinetic parameters of oxfendazole were estimated using noncompartmental analysis. Oxfendazole was rapidly absorbed with mean plasma half-life ranging from 8.5 to 11 hours. The renal excretion of oxfendazole was minimal. Oxfendazole exhibited significant nonlinear pharmacokinetics with less than dose-proportional increases in exposure after single oral doses 0.5 mg/kg to 60 mg/kg. This nonlinearity of oxfendazole is likely due to the dose-dependent decrease in bioavailability that is caused by its low solubility. Oxfendazole was found to be well-tolerated in this study at different escalating doses without any serious adverse events (AEs) or deaths. There were no significant differences in the distribution of hematology, biochemistry or urine parameters between oxfendazole and placebo recipients.
  • Article
    Introduction. Oxfendazole (methyl [5-(phenylsulphinyl)-1H benzimidazole- 2-yl] carbamate) has a particularly long metabolic half-life in ruminants, and its metabolite fenbendazole also has anthelminthic action. A very limited number of drugs are available for the treatment of some zoonotic helminth infections, such as neurocysticercosis and echinococcosis. More recent work has expanded oxfendazole’s non-clinical safety profile and demonstrated its safety and bioavailability in healthy human volunteers, thus advancing the possibility of a new and greatly needed option for antiparasitic treatment of geohelminths and tissue parasites. Areas covered. The present article reviews evidence supporting the safety and efficacy of oxfendazole against both gut and tissue dwelling helminths in animals, as well as more recent safety and pharmacokinetic data supporting its potential for use in human parasitoses. Expert commentary. The pharmacokinetics, safety and wide spectrum of efficacy of oxfendazole are consistently demonstrated in intestinal helminth infections of animals as well as in tissue dwelling larval cestode and trematode infections in diverse animal species. Now supported by first-in-human safety and pharmacokinetic data, oxfendazole becomes a promising alternative to the limited portfolio of antiparasitic drugs available to treat helminthic diseases of humans.
  • Chapter
    Cestodes, or tapeworms, vary greatly in size and behavior but have similar morphology consisting of a head, called a scolex, a neck, and a worm body, called a strobila, which is formed by body segments called proglottids. T. saginata, T. solium, and T. asiatica. The life cycles of these Taenia species are similar. As definitive host, humans acquire intestinal infection with these cestodes by ingestion of undercooked meat—pork in the case of T. solium and T. asiatica and beef in the case of T. saginata—containing encysted larvae termed cysticercus. This tapeworm infection is called taeniasis. As intermediate host, humans acquire tissue infection of cysticerci by ingestion of T. solium eggs. After ingestion, the eggs mature into metacestodes, which are infective larvae capable of encysting in tissues. This infection is called cysticercosis. T. solium is the only species known to cause significant human pathology; most commonly larvae encyst in the central nervous system (CNS), which is called neurocysticercosis. T. saginata and T. asiatica are similar morphologically and closely related genetically. They cause limited pathology in humans but significant economic losses in the livestock industry.
  • Bulletin of the World Health Organization 71 The Veternary Record Guidelines for surveillance prevention and control of taeniasis and cisticercosis. VPH doc 8349 Bulletin of the Panamerican Health Organization 27
    • P Szyfres
    • B Cruz
    • M Davis
    • A Dixon
    • H Pawlowski
    • Z S Proano
    • Cysticercosis Working Group In Peru Diaz
    • S P Candil
    • A Suate
    • V Zazueta
    • M L Felix
    • M Lozano
    • R Willms
    • K Flisser
    • A Gonzalez
    • D Shkurovich
    • M Madrazo
    • I Correa
    • J Cohen
    • E Collado
    • M Fernandez
    • B Fernandez
    • F De Aluja
    • A S Garcia
    • H H Gilman
    • R Martinez
    • M Tsang
    • V C W Pilcher
    • J B Herrera
    • G Diaz
    • F Porras
    • M Alvarado
    • M Orrillo
    • E Torres
    • P Miranda
    • E Cysticercosis Working Group In Peru Garcia
    • H H Martinez
    • M Gilman
    • R H Herrera
    • G Tsang
    • V C W Pilcher
    • J B Diaz
    • F Verastegui
    • M Gallo
    • C Porras
    • M Alvarado
    • M Naranjo
    • J Miranda
    • E Cysticercosis Working Group In Peru Gemmell
    • M A Matyas
    • R Pawlowski
    • S Z Soulsby
    • E S L Gonzalez
    • A E Cama
    • V Gilman
    • R H Tsang
    • V C W Pilcher
    • J B Chavera
    • A Castro
    • M Montenegro
    • T Verastequi
    • M Miranda
    • E Bazalar
    • H Gonzalez
    • A E Garcia
    • H H Gilman
    • R H Gavidia
    • C Tsang
    • V C W Bernal
    • T Falcon
    • N Romero
    • M Lopez-Urbina
    • M T Gonzalez
    • A E Garcia
    • H H Gilman
    • R H Lopez
    • M T Gavidia
    • C Mcdonald
    • J Pilcher
    • J B Tsang
    • V C W Murrel
    • K D Nash
    • T E Neva
    • F A Schantz
    • P M Cruz
    • M Sarti
    • E Pawlowski
    • Z Tellez-Giron
    • E Ramos
    • M C Montante
    • M Tsang
    • V C W Pilcher
    • J A Zhou
    • W Boyer
    • A Kamango
    • E Sollo
    • M L Rhoads
    • D Murrel
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  • Article
    Reimpresión en 2003 Incluye bibliografía e índice v. 1 Bacteriosis y micosis -- v. 2. Clamidiosis, rickettsiosis y virosis -- v. 3. Parasitosis
  • Economic losses resulting from food-borne parasitic zoonoses are difficult to assess. Estimating the global economic impact of these diseases is handicapped by inadequate information on the prevalence and public health importance of parasitic zoonoses for most countries. However, the economic losses caused by certain zoonoses has been estimated for some regions and in these instances the costs are significant. In Mexico, for example, porcine cysticercosis is responsible for a loss of more than one-half of the national investment in swine production and for more than US$17 million annually in hospitalization and treatment costs for humans with neurocysticercosis. For all of Latin America, porcine cysticercosis accounts for an economic loss of US$164 million. In Africa, losses of one to two billion dollars per year due to bovine cysticercosis have been reported. Human toxoplasmosis in the United States is estimated to be an annual economic/public health burden of more than US$400 million. The implication from these examples and other are discussed. A set of recommendations is presented for obtaining the necessary information needed to permit assigning to food-borne parasitic zoonoses their appropriate priority within each country's complex economic and public health problems.
  • Article
    An increasing amount of information is becoming available from parasitological, biochemical and immunological laboratories and much of it is on subjects directly related to human health (taeniasis/ cysticercosis, strongyloidiasis, ascariasis). This is probably a reflection of the current policies of the various funding agencies. However, interest in some subjects (e.g. human trematodes, large-scale anthelmintic trials) is clearly a result of the new developments in anti-parasitic drugs. There are, nevertheless, some areas (strongyloidiasis and trichuriasis) where more laboratory and immunological research is needed. Better understanding of several clinical pathology problems requires stronger links between the clinics and parasitological laboratories.The importance of field research (Garnham, 1979) is still underestimated, which explains considerable gaps between the knowledge needed and that which is available as well as between what is available and what is applicable.A quantitive approach and studies on population dynamics have become important for the practical control of intestinal helminthiasis. However, ecological, environmental, behavioural and social studies, have not been able to explain the changing pattern of some infections (trematodiasis) or the persistence of others (taeniasis, ascariasis).Changes in health priorities towards primary health care and greater emphasis on prevention and control are opening up new perspectives for cooperation between parasitologists and the human health services (Pawlowski, 1986).
  • Article
    The effect of flubendazole on Cysticercus cellulosae was tested in 15 pigs. In doses o 8.3 mg/kg body weight or more daily for 10 days the drug was lethal to the cysticerci, causing both macroscopic and microscopic morphological alterations. An in vitro test showed 0% viability of cysticerci in most of the treated pigs, whereas in 90-100% of 11 control pigs they were viable.
  • Article
    In a randomized, controlled study, the efficacy and safety of two different schemes of albendazole therapy for treatment of porcine cysticercosis were tested. Seventeen naturally infected pigs were divided into three groups and treated per os with albendazole (50 mg/kg single dose), albendazole (30 mg/kg every day for three days), or given no treatment, respectively. Serologic responses were monitored with the enzyme-linked electroimmunotransfer blot assay. Pigs were humanely killed 12 weeks after treatment, necropsied, and the number of parasites was recorded. Scolex evagination was used to assess viability of the cysts. Both albendazole-treated groups had significant side effects (anorexia, lethargy). Only a single viable cyst was recovered from the brain of one animal after therapy in the multiple-dose group, and the single-dose therapy left 11% of the cysts viable. In contrast, more than 90% of muscle cysts were found to be viable in the untreated group. Although albendazole therapy for three days was found to be highly effective, side effects and the need for multiple doses would still prevent its widespread use.