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Received: 26 April 2018    Revised: 27 September 2018    Accepted: 2 October 2018

DOI: 10.1111/jvp.12735

REVIEW ARTICLE

Use of praziquantel to control platyhelminth parasites of fish

Chris Bader1 | David E. Starling2 | Douglas E. Jones1 | Matthew T. Brewer1

1
Department of Veterinary Pathology, Iowa
State University College of Veterinary
Medicine, Ames, Iowa
2
Department of Biomedical Sciences, Iowa
State University College of Veterinary
Medicine, Ames, Iowa
Correspondence
Matthew T. Brewer, Department of
Veterinary Pathology, Iowa State University
College of Veterinary Medicine, Ames, IA.
Email: brewermt@iastate.edu
Funding information
This work was supported by start-­up
funds provided to MTB by the Iowa State
University College of Veterinary Medicine
and the President’s initiative for wildlife
research at Iowa State University.
Abstract
Fish are common definitive and intermediate hosts for a variety of parasitic flat-
worms. In unstressed wild populations, parasitic infections often go unnoticed and
are perceived to represent a lesser threat to fish health. In contrast, platyhelminth
parasitism of captive fish often results in decreased weight gain and increased mor-
tality which often necessitates chemotherapeutic treatment. The presence of platy-
helminth parasites in fish tissues is not only unappealing but in some cases also
represents a threat to human health. In veterinary medicine, one of the most com-
monly used agents with anti-­flatworm activity is praziquantel; yet, no praziquantel
products are labeled for use in fish in the United States. Veterinarians may use prazi-
quantel preparations approved for other vertebrate species under the Animal
Medicinal Drug Use Clarification Act (AMDUCA). However, such extra-­label use
should be informed by scientific evidence including efficacy and tissue residue stud-
ies. Herein, we review studies testing the efficacy of praziquantel for treatment of
platyhelminthes along with an assessment of routes of administration, pharmacoki-
netics, and toxicity information.

1 |  I NTRO D U C TI O N Praziquantel (Figure 1) is a synthetic drug that was discov-

Parasitic flatworms of the phylum Platyhelminthes represent a di-
verse spectrum of organisms that infect (live within) and infest (live
upon) vertebrates. The monogeneans are propagated by a direct life
cycle whereby adult helminths live on the definitive host, reproduce
sexually, and shed ova or larvae which enter the environment and
eventually infest a new definitive host. In contrast, cestodes and
trematodes employ indirect life cycles whereby an intermediate
host is required for larval development and/or asexual multiplication
before returning to the definitive host. Fish serve as both definitive
and intermediate hosts for a spectrum of platyhelminth parasites.
There is a breadth of platyhelminth parasite taxa that infect fish,
and the consequences of infection vary according to the location of
the parasite in the host. Similarly, the need to intervene and treat
infected or infested animals depends on the intensity of parasite
load. In production aquaculture, it becomes necessary to treat fish
to prevent economic losses. In other cases, fish may contain larval
cestodes or trematodes that are infectious for humans, thereby re-
quiring treatment. In addition, aquarium or ornamental fish may re-
quire treatment.
ered by Bayer in the 1970s (Adam, Elwasila, & Homeida, 2005).
Remarkably, praziquantel is effective against a broad range of ces-
todes (tapeworms) and trematodes (flukes) and is a mainstay of
anti-­platyhelminth parasite therapy in both human and veterinary
medicine. Despite being widely studied and used, the precise mech-
anism of action of praziquantel remains a subject of investigation.
Following exposure to the drug, there is disruption of the worm teg-
ument which is characterized by vacuolization and blebbing (Staudt,
Schmahl, Blaschke, & Mehlhorn, 1992). This process is thought to
be related to binding voltage-­gated Ca2+ channels and disruption of
Ca2+ homeostasis via altering membrane permeability (Doenhoff,
Cioli, & Utzinger, 2008). There is also evidence that praziquantel-­
induced damage to the tegument renders the parasite more suscep-
tible to immune-­mediated clearance (Ribeiro, Mello, Tavares, Kusel,
& Coelho, 2004). These effects are specific to platyhelminthes,
and praziquantel has a wide margin of safety, at least in mammals
(Frohberg, 1984).
Currently, the only agents labeled for use against parasites in fish
are dilute formalin preparations (U. S. Food and Drug Administration,
2016). These preparations are only labeled for monogeneans

J vet Pharmacol Therap. 2019;42:139–153. © 2018 John Wiley & Sons Ltd |  139
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140       BADER et al.
(discussed herein) but not for cestodes or digenean trematodes.
Because there are no drugs labeled for digenean trematode and ces-
tode parasites, veterinarians may justify off-­label use of praziquantel
within the framework of the Animal Medicinal Drug Use Clarification
Act (AMDUCA). In addition, AMDUCA may allow for the use of
praziquantel in situations where formalin cannot be utilized. For ex-
ample, formalin cannot be added to certain systems due to damaging
effects on biofilters thereby indirectly increasing harmful ammonia
levels in the water (Keck & Blanc, 2002). When considering off-­label
use, it is important to evaluate the data available for the particular
host and parasite species being addressed. In this manuscript, we
review the body of knowledge regarding the use of praziquantel for
treatment of monogeneans, digenean trematodes, and cestodes in-
fecting fish.
2 |  E FFI C AC Y: M O N O G E N E A N S
Monogeneans are larviparous or oviparous ectoparasites of fish skin
and gills. They utilize direct life cycles and can be transferred from
host to host through direct or indirect contact. In aquaculture sys-
tems, dangerous levels of monogenean parasites may accumulate.
Damage caused by feeding monogeneans can lead to tissue damage
which often leads to secondary microbial infections. Monogenean
parasitism of gills can cause gill hyperplasia and mucous produc-
tion leading to suffocation and death, inducing high levels (>80%) of
mortality when high parasite burdens are present (Thoney & Hargis,
1991).
Dilute formalin preparations are labeled only for the monogene-
ans Cleidodiscus, Dactylogyrus, and Gyrodactylus (U. S. Food and Drug
Administration, 2016). Formalin is approved for these monogeneans
as a bath treatment. In a variety of situations, formalin may not be a
feasible treatment. For example, formalin can cause serious insult to
gills, eyes, and skin. In addition, formalin indirectly reduces dissolved
oxygen from the water and contains algicidal and bactericidal activ-
ity which can damage biofilters (Neely, 1963). In addition, extremely
cold water environments may lead to increased conversion of form-
aldehyde into paraformaldehyde which is more toxic to fish (Rucker,
Taylor, & Toney, 1963). In addition, approved bath treatments may
not be feasible in large volumes of water. Formalin is not approved
for administration via parenteral or oral routes.
Several studies have tested the efficacy of praziquantel vs.
various monogenean parasites, and these studies are summarized
in Table 1. In our review of the literature, we found only a single
study reporting poor efficacy (33%) for praziquantel when used
to treat Microcotyle sebastis with 100 mg/Kg oral treatment in
rockfish (Kim, Park, & Jee, 1998). In general, bath and dip treat-
ments are effective for removing monogeneans and this is not
surprising due to the location of the parasites on the surface
of the fish host (Bader, Jesudoss Chelladurai, Starling, Jones,
& Brewer, 2017,2018; Bader, Jesudoss Chelladurai, Thompson,
Starling, & Brewer, 2017). There are also a smaller group of
monogeneans that infect the tissues of fish such as Acolpenteron
spp. These monogeneans appear to be killed by praziquantel
in vitro, and future studies are likely to show susceptibility of
the parasite in vivo (Reimschuessel, Gieseker, & Poynton, 2011).
Praziquantel appears most effective against adult forms of mono-
geneans, and it is unclear if eggs can be killed using praziquan-
tel. Some studies have suggested that praziquantel is ineffective
against eggs (Morales-­S erna et al., 2018), and new methods of
assessing egg death would be valuable to investigate this further.
Bath treatments ranging from 2 to 200 mg/ml have been inves-
tigated, and these treatments are typically applied for 24–48 hr.
Monogeneans have the ability to detach and survive in the envi-
ronment for a short period of time before reattaching to a new
host (Schmahl & Taraschewski, 1987). This gives them the oppor-
tunity to avoid the praziquantel for short periods of time during
oral treatments. A bath treatment, however, will ensure that
even when parasites detach they remain in a treated environ-
ment (Sharp, Diggles, Poortenaar, & Willis, 2004). Interestingly,
several studies have also revealed that oral praziquantel admin-
istration was effective for removing monogeneans. Given the
high success of praziquantel treatment for monogeneans and the
potential problems with formalin administration, praziquantel
bath treatments pose a viable substitution for fish infected with
monogenean parasites. Praziquantel does not target bacteria or
viruses and does not have the potential to damage essential mi-
crobes in biofilters. In light of the concerns associated with for-
malin administration, praziquantel would be a suitable substitute
for treatment of monogeneans.
One challenge in assessing efficacy studies for monogeneans is
the ability to reliably detect parasite death. Often, parasite counts
are compared on treated and control animals. However, it is unclear
if organisms can be killed, yet still attached to the host. It would also
be useful to have standardized methods for detecting death in imma-
ture stages and eggs, which are of interest in such efficacy studies.
It is possible that different cell viability staining methods can reveal
monogenean death. However, detection of death with different
stains could be dependent on mode of action for a particular drug.
Going forward, there is a need for methods that can rapidly and ob-
jectively measure death of monogeneans.
F I G U R E   1   Structure of (R)-­praziquantel, the enantiomeric
active form of praziquantel [Colour figure can be viewed at
wileyonlinelibrary.com]
BADER et al. |
      141

TA B L E   1   Efficacy of praziquantel treatments on adult monogeneans. When multiple treatments reached 100% efficacy against the given
monogenean, only the lowest dose is reported

Parasite Host Route Dose Efficacy Source

Ancylodiscoides vistulensis European catfish Bath 10 mg/L for 15% 3–4 days Szekely and Molnar
5 hr post-treatment (1990)
Benedenia seriolae Yellowtail amberjack Feed 50 mg/kg for 58.1 Williams, Ernst,
6 days Chambers, and
Whittington (2007)
Benedenia. seriolae Yellowtail amberjack Bath 2.5 mg/L for >99% Sharp et al. (2004)
24 hr
Benedenai seriolae Yellowtail Kingfish Feed 70 mg/Kg daily 99.7% Forwood, Bubner,
for 3 days Landos, Deveney,
and D’Antignana
(2016)
Benedeniella posterocolpa Cownose rays Dip 20 mg/L for 100% Thoney (1990)
90 min
Cleidodiscus sp. Black Crappie Bath 1.5 mg/L for >80% Bader, Jesudoss
24 hr Chelladurai, Starling,
Jones et al.
(2017,2018); Bader,
Jesudoss
Chelladurai,
Thompson et al.
(2017)
Clemacotyle australis White-­spotted eagle Bath 25 mg/L for 100% Janse and Borgsteede
rays 45 min (2003)
Dactylogyrus intermedius Goldfish Bath 13.5 mg/L for 93% 6 days Zhang, Ling, Chi, and
48 hr post-treatment Wang (2013)
Dactylogyrus sp. Guppy Bath 3 mg/L for 100% Fridman, Sinai, and
24 hr Zilberg (2014)
Gyrodactylus aculeati Stickleback Bath 10 mg/L for 100% Schmahl and
16 hr Taraschewski (1987)
Gyrodactylus aculeati Stickleback Bath 20 mg/L for 100% Schmahl and
2 hr Taraschewski (1987)
Gyrodactylus sp. Rainbow trout Dip 10 mg/ml for 97.7% Santamarina, Tojo,
3 hr Ubeira, Quinteiro,
and Sanmartin
(1991)
Gyrodactylus sp. Rainbow trout Dip 100 mg/ml for 100% Santamarina et al.
60 min (1991)
Gyrodactylus turnbulli Guppy Bath 3 mg/L for 71.1% Fridman et al. (2014)
24 hr
Haliotrema abaddon West Australian Bath 2 mg/L for ~100% Fajer-­Ávila,
dhufish 30 hr Velásquez-­Medina,
and Betancourt-­
Lozano (2007)
Heterobothrium okamoti Takifugu rubripes Feed 40 mg/kg for 100% Hirazawa, Ohtaka,
20 days and Hata (2000)
Lepidotrema bidyana Silver perch Bath 10 mg/L for 99% Forwood et al.
48 hr (2013a)
Lepidotrema bidyana Silver perch Bath 40 mg/L for 77% Forwood et al.
24 hr (2013b)
Lepidotrema bidyana Silver Perch Feed 75 mg/kg daily 79% Forwood et al.
for 6 days (2013a)

(Continues)
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142       BADER et al.

TA B L E   1   (Continued)

Parasite Host Route Dose Efficacy Source

Microcotyle sebastis Rockfish Feed 100 mg/kg 33.3% Kim et al. (1998)

single
treatment
Microcotyle sebastis Rockfish Feed 200 mg/kg 100% Kim et al. (1998)
single
treatment
Neobenedenia girellae Chub mackerel Feed 150 mg/kg for >80% Yamamoto et al.
3 days (2011)
Zeuxapta seriolae Yellowtail amberjack Bath 2.5 mg/L for 100% Sharp et al. (2004)
24 hr
Zeuxapta seriolae Yellowtail amberjack Bath 2.5 mg/L for 100% Sharp et al. (2004)
48 hr
Zeuxapta seriolae Yellowtail amberjack Feed 50 mg/kg for 81.4% Williams et al. (2007)
6 days
Zeuxapta seriolae Yellowtail Kingfish Feed 70 mg/Kg daily 81.7% Forwood et al. (2016)
for 3 days

3 |  E FFI C AC Y: D I G E N E A N S
Digenean trematodes have diverse and complex indirect life cycles.
The most common life cycle follows that eggs are voided from the
definitive host, and a miracidium hatches and penetrates a snail.
Following asexual replication in the snail, cercaria is released; this
larval stage then encysts on a second intermediate host or on veg-
etation prior to being ingested by the definitive host. Fish may
serve as definitive hosts for digeneans, but they are also common
intermediate hosts for flukes that infect other vertebrate defini-
tive hosts. Larval digenean trematodes present in the tissues of fish
are termed metacercariae or metacercarial cysts. In the cases of
Heterophyes, Echinostoma, Clonorchis, and others, humans can serve
as definitive hosts and become infected following ingestion of meta-
cercariae in undercooked fish (Chai, Darwin Murrell, & Lymbery,
2005; Hedegaard Clausen et al., 2012; Li, Clausen, Murrell, Liu, &
Dalsgaard, 2013). Many other genera of digenean adults parasitize
avian and mammalian hosts that consume fish prey. Therefore,
metacercariae can be a threat to human and veterinary health or
be unappetizing features of fish fillets. Metacercariae do not multi-
ply within the fish and therefore do not typically represent a direct
threat to fish health even when they infect sensitive organs such
as the brain, or nervous system (Khalil, 1968). However, infection
with large numbers of metacercariae can be clinically significant
(Hoffman, 1958). Adult trematodes are relatively nonpathogenic in
fish unless present in large numbers. For example, blood flukes can
cause considerable damage to gills by obstructing the passage of
blood and can cause anemia leading to production losses (Hoffman,
Fried, & Harvey, 1985) (Evans, 1974).
There are currently no drugs labeled for the treatment of dige-
nean trematodes in fish. However, several studies have assessed
the efficacy of praziquantel for treatment of both metacercariae
and adult digenean trematodes (Table 2). Oral formulations of prazi-
quantel removed 91%–100% of adult Cardicola blood flukes. Studies
investigating metacercariae of Clinostomum and Diplostomum range
from 68% to 100% efficacy. Different host fish species may re-
quire different doses for treatment of the same parasite. Szekely
and Molnar (1991), found a dramatic decrease in efficacy of a bath
treatment in silver carp as opposed to grass carp parasitized with
Diplostomum spathaceum. It is possible that differences in efficacy
among host species are related to host metabolism and tissue distri-
bution, although additional work is needed to confirm this.
Interestingly, several studies involving the elimination of meta-
cercariae were achieved by bath treatment (Lorio, 1989; Plumb &
Rogers, 1990; Szekely & Molnar, 1991). This was somewhat surpris-
ing given the intramuscular location of the parasites, and the lim-
ited knowledge of pharmacokinetics from bath treatments. The only
study assessing pharmacokinetics of bath treatments found a very
low maximum concentration (0.49 μg/L) when rockfish were sub-
jected to 100 mg/L praziquantel bath treatment for 4 min (Kim, Kim,
Kim, & Kim, 2001).
A challenge with studies involving metacercariae is that metacer-
carial death is often measured as determined by movement and this
may be unreliable, as many encysted metacercariae have limited mo-
bility (Asanji & Williams, 1975). In addition, metacercariae that have
died may take extended time to be removed by the host response.
Therefore, counting the total number of metacercariae immediately
following treatment may not reveal differences in treated and un-
treated fish. Additional techniques for determining death of meta-
cercariae are needed in order to advance research in this area. One
useful method for detecting metacercarial death is propidium iodide
staining. Propidium iodide stains cells with compromised mem-
branes. Metacercariae extracted from treated fish can be stained
by propidium iodide ex vivo, and the level of staining is proportional
TA B L E   2   Efficacy of praziquantel treatments on adult digeneans

Parasite Definitive/Intermediate host Host Route Dose Efficacy Source

BADER et al.

Cardicola forsteri Definitive Pacific Bluefin Feed 150 mg/kg single dose 91% 24 days Hardy-­Smith et al. (2012)
Tuna post-treatment
Cardicola forsteri Definitive Pacific Bluefin Feed 75 mg/kg single dose 95% 24 days Hardy-­Smith et al. (2012)
Tuna post-treatment
Cardicola forsteri Definitive Pacific Bluefin Feed 15 mg/kg for 3 days 100%, eggs still viable Shirakashi et al. (2012)
Tuna
Cardicola opisthorchis Definitive Pacific Bluefin Feed 7.5 mg/kg for 3 days 100% Ishimaru et al. (2013)
Tuna
Clinostomum complanatum Intermediate Sunshine bass Bath 0.25 mg/L for 24 hr 100% Mitchell (1995)
Clinostomum marginatum Intermediate Channel catfish Bath 0.65 mg/L + 15 mg/kg 80.2% 5.5 months Lorio (1989)
for 24 hr post-treatment
Clinostomum marginatum Intermediate Channel catfish Bath 2 mg/L for 2 hr 100% 21 days Plumb and Rogers (1990)
post-treatment
Clinostomum marginatum Intermediate Channel catfish Bath 2 mg/L for 4 hr 50% 21 days Plumb and Rogers (1990)
post-treatment
Clinostomum marginatum Intermediate Channel catfish Injection 25 mg/kg 73.6% 5.5 months Lorio (1989)
post-treatment
Diplostomum spathaceum Intermediate Barbel Bath 10 mg/L 73.6% 5.5 months Zuskova et al. (2018)
post-treatment
Diplostomum spathaceum Intermediate Channel catfish Bath 2 mg/L for 4 hr 90.1% 21 days Plumb and Rogers (1990)
post-treatment
Diplostomum spathaceum Intermediate Grass carp Bath 1 mg/L for 24 hr  80.2% Szekely and Molnar (1991)
Diplostomum spathaceum Intermediate Grass carp Bath 1 mg/L for 90 hr  100% Szekely and Molnar (1991)
Diplostomum spathaceum Intermediate Grass carp Dip 50 mg/L for 20 min 94.4% Szekely and Molnar (1991)
Diplostomum spathaceum Intermediate Grass carp Dip 100 mg/L for 20 min 75.3% Szekely and Molnar (1991)
Diplostomum spathaceum Intermediate Grass carp Feed 330 mg/kg 100% Szekely and Molnar (1991)
Diplostomum spathaceum Intermediate Silver carp Bath 1 mg/L for 24 hr  68.6% Szekely and Molnar (1991)
Diplostomum spathaceum Intermediate Silver carp Dip 50 mg/L for 20 min 96.8% Szekely and Molnar (1991)
Posthodiplostomum minimum Intermediate Bluegill Intramuscular 5 mg/kg ~100% Bader, Jesudoss
injection Chelladurai, Starling,
Jones et al. (2017,2018);
Bader, Jesudoss
Chelladurai, Thompson et
al. (2017)

When multiple treatments reached 100% efficacy against the given digeneans, only the lowest effective dose is reported. When a higher concentration reported a lower efficacy, both treatments were
included.
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      143
TA B L E   3   Efficacy of praziquantel treatments on cestode parasites
|

Parasite Definitive/Intermediate host Host Route Dose Efficacy Source

144      

Atractolytocestus Definitive Common carp Intubation 50 mg/kg single 100% 4 days Sudová, Piačková, Velíšek, Pijáček, and
huronensis dose post-treatment Svobodová (2010)
Bothriocephalus Definitive Bonytail chub Bath 1.5 mg/L for 24 hr 100% Ward (2007)
acheilognathi
Bothriocephalus Definitive Grass Carp Bath 0.25 mg/L for 24 hr 100% Mitchell (2004)
acheilognathi
Bothriocephalus Definitive Grass Carp Bath 0.75 mg/L for 24 hr 100% Mitchell and Darwish (2009)
acheilognathi
Bothriocephalus Definitive Grass Carp Bath 1.5 mg/L for 12 hr 86.70% Mitchell and Darwish (2009)
acheilognathi
Bothriocephalus Definitive Grass Carp Bath 12 mg/L for 6 hr 90% Mitchell and Darwish (2009)
acheilognathi
Bothriocephalus Definitive Grass Carp Bath 2.8 mg/L for 12 hr 100% Mitchell (2004)
acheilognathi
Bothriocephalus Definitive Grass Carp Bath 9 mg/L for 12 hr 66.7% Mitchell and Darwish (2009)
acheilognathi
Bothriocephalus Definitive Grass Carp Feed 35 mg/kg for 3 days 100% Pool et al. (1984)
acheilognathi
Bothriocephalus Definitive Red Shiner Bath 2.5 mg/L, for 100% 2.5 Mitchell and Darwish (2009)
acheilognathi 19 days post-treatment
Bothriocephalus scorpii Definitive Red snapper Bath 6 mg/L for 24 hr 100% Kline et al. (2009)
Bothriocephalus scorpii Definitive Turbot Intubation 5 mg/kg for 3 days 100% Sanmartín Durán, Caamaño-­García,
Fernández Casal, Leiro, and Ubeira
(1989)
Khawia sinensis Intermediate Common carp Intubation 50 mg/kg single 100% 6 days Sudová et al. (2010)
dose post-treatment

When multiple treatments reached 100% efficacy against the given cestode, only the lowest effective dose is reported. When a higher concentration reported a lower efficacy, both treatments were
included.
BADER et al.
BADER et al.
to the dose of praziquantel for Posthodiplostomum metacercariae
(Bader, Jesudoss Chelladurai, Starling, Jones et al., 2017,2018; Bader,
Jesudoss Chelladurai, Thompson et al., 2017). This method is at least
as sensitive as motility scoring and provides a quantitative assess-
ment of metacercarial death (Bader, Jesudoss Chelladurai, Starling,
Jones et al., 2017,2018; Bader, Jesudoss Chelladurai, Thompson
et al., 2017). Future studies would benefit from using this quanti-
tative method since it could be used to compare the relative level
of praziquantel susceptibility or resistance among different parasite
isolates.
4 | E FFI C AC Y: C E S TO D E S
Cestodes can typically be found in the small intestine of the definitive
host. Like digeneans, cestodes require an intermediate host for larval
(metacestode) development. Fish may be either the definitive hosts
or intermediate hosts. For some parasites such as Diphyllobothrium,
fish are the intermediate hosts for cestodes that infect humans. Like
digeneans, there are no drugs labeled for use against cestodes in
fish. Some cestodes have a free-­living stage, but it is short-­lived as
compared to life cycle stages present in fish. Therefore, praziquantel
treatment represents a viable strategy to maintain control of these
parasites in fish.
The majority of the research investigating the use of praziquantel
to treat cestodes involves fish that are definitive hosts of the inva-
sive Asian tapeworm Bothriocephalus acheilognathi (Table 3). Bath
treatments were effective for this gastrointestinal parasite, remov-
ing 66%–100% of adult parasites from the intestinal lumen (Kline,
Archdeacon, & Bonar, 2009; Mitchell, 2004; Mitchell & Darwish,
2009; Pool, Ryder, & Andrews, 1984; Ward, 2007). Adults of Khawia
sinensis, Atractolytocestus cestus, and Bothriocephalus sp. were also
removed following oral treatment with praziquantel (Pool et al.,
1984). These experiments suggest that the praziquantel bath is in-
gested thereby killing adult cestodes within the lumen of the intes-
tine. It appears that cestodes are susceptible to praziquantel with
doses as low as 0.25 mg/L for 24 hr which was 100% efficacious for
Bothriocephalus acheilognathi in sunshine bass (Mitchell, 2004). In
summary, there is evidence that adult cestodes can be removed from
fish by praziquantel. Going forward, there is a need to determine
whether praziquantel can be used to remove larval cestodes such as
Diphyllobothrium from fish tissues.
5 | RO U TE O F A D M I N I S TR ATI O N
In terrestrial vertebrates, praziquantel is typically administered
orally or parenterally. In aquaculture systems, there are often thou-
sands of individual fish in a single facility and this poses a challenge
in terms of administering medication. Potential routes of adminis-
tration include oral, injectable, and topical (baths and dips); each of
which have advantages and disadvantages. Relatively little research
has involved head to head comparison of different administration
|
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routes for a particular parasite. The host, the environment, and the
target parasite should be taken into account when selecting route of
administration.
Oral administration of praziquantel is especially desirable when
treating platyhelminthes that reside in the gastrointestinal tract, such
as cestodes. For large populations of fish, the most convenient form
of oral treatment is in-­feed medication. However, there are several
disadvantages to this approach. For example, food may be consumed
disproportionately therefore providing individuals with different
doses of medication. This is especially problematic since parasitized
animals can have a decreased food intake, leading to subtherapeutic
doses being administered (Crompton, 1984). Additionally, fish will
establish feeding hierarchies which can lead to an uneven distribu-
tion of treatment and potential subtherapeutic dosing of individual
fish (Samaee, 2015). Such dosing has the potential to lead to promo-
tion of parasite drug resistance (Shalaby, 2013). It can take extensive
time for fish to become acclimated to just artificial feed; it may take
several weeks to acclimate fish to such a new diet (Moura, Kubitza,
& Cyrino, 2000). Therefore, it may not be practical to implement in-­
feed treatment if the fish are not acclimated to a pelleted diet.
Another challenge for feed-­based administration of praziquantel
is its bitter taste which is known to lead to decreased consumption
(Partridge, Michael, & Thuillier, 2014). To combat problems with pal-
atability, preparations consisting of the (R)-­enantiomer may be used
instead of racemic mixtures since the (S)-­enantiomer is responsi-
ble for the bitter taste, and only has limited anthelmintic properties
(Meyer et al., 2009). However, this may not be the ultimate solution
since the (R)-­enantiomer has a stronger smell which decreased feed
consumption at levels of 10 mg/Kg (Partridge, Burge, & Lymbery,
2016). Other methods have been investigated for masking the taste,
including mixing with fish oil, krill extracts, sugar, or commercial fish
attractants (Yamamoto, Shirakashi, Morimoto, Ishimaru, & Murata,
2011). Another strategy for stimulating consumption is to withhold
feed briefly prior to introduction of medicated pellets (Pool et al.,
1984). Gastric intubation has also been performed (Tubbs & Tingle,
2006), which is more stressful to the fish but allows for the direct
control of the dosing of each fish. Gavage feeding may represent an
option when a small number of individuals require treatment.
Although there are challenges associated with in-­
feed treat-
ment, this route of administration is particularly attractive due to the
possibility of treating an entire population of fish without handling
individual animals. Unfortunately, there are no formulations of prazi-
quantel available for use in feed. In the research literature, a variety
of methods have been employed in order to prepare praziquantel for
feeding. For example, praziquantel has been suspended in cooking
oil or added to carboxymethyl cellulose sodium (CMC) as a sticking
agent for distribution onto commercial feed (Ishimaru et al., 2013;
Pool et al., 1984). Alternatively, a praziquantel paste has been pre-
pared and mixed with feed prior to pelleting to create a medicated
feed (Kim, Cho, Ahn, Lee, & Kim, 2003). Although these methods
have been demonstrated experimentally, it is unclear whether this
strategy could be implemented in a commercial aquaculture facility.
 |
146       BADER et al.
Relatively little research has assessed injectable praziquantel
for fish, with only two studies examining the effects on digene-
ans in channel catfish (Lorio, 1989) and bluegill (Bader, Jesudoss
Chelladurai, Starling, Jones, & Brewer, 2018). There has also been a
single study on the pharmacokinetics of intravenously injected prazi-
quantel in yellow amberjack (Tubbs & Tingle, 2006). This is probably
related to the fact that increased handling of the fish become time
intensive and expensive. Another concern is that increased handling
of fish can lead to stress and mortality events (Midtlyng, 1997).
Injectable forms of praziquantel are available for other domestic an-
imal species, and this could be attractive in certain situations where
only a small number of individuals need to be treated. Parenteral
praziquantel may also be desirable for treating tissue-­dwelling platy-
helminthes such as larval digeneans and cestodes.
A third possible route of administration is topical via bath or dip
treatment whereby praziquantel solution is added directly to the
water for a defined amount of time. Topical administration is par-
ticularly desirable when targeting monogenean ectoparasites. By
convention, a bath treatment typically involves a low concentration
of drug for an extended period of time, whereas a dip utilizes a high
concentration of drug for an abbreviated timeframe. Both methods
provide a uniform treatment to each fish (Samuelsen & Lunestad,
1996). Stocking density should be taken into account when admin-
istering bath treatments. For instance, Mitchell and Darwish (2009)
found a significant decrease in efficacy when providing identical
bath treatments to grass carp at a stocking density of 120 g of fish
per liter instead of 60 g of fish per liter. Future studies should assess
calculation of topical doses on a weight per weight basis in addition
to weight per volume of water. The observation that treatments ad-
ministered in the water are effective for some tissue-­dwelling dige-
neans and cestodes is interesting. It thought to occur by praziquantel
being absorbed mainly through the gills, with small amounts being
absorbed through the skin (Kim, Kim et al., 2001).
Praziquantel may be administered in oral, injectable, or topical
forms, and the most appropriate route of administration should be
determined in the context of the target species, parasites, and laws
regarding extra-­label administration. While ornamental fish may be
treated at any time, it is important to establish withdrawal periods
for each route of administration so that fish intended for human con-
sumption avoid drug residue violations.
6 |  PH A R M ACO K I N E TI C S A N D TI S S U E
RESIDUES
When administering antiparasiticides, it is important to consider
tissue distribution and elimination of the proposed treatment.
Platyhelminthes can occur in a variety of locations, and one must
ensure that the anthelmintic is reaching the desired target tissue.
Following oral administration in fish, praziquantel is distributed
throughout the animal, including muscle, kidney, plasma, and liver.
Praziquantel is metabolized into cis-­and trans-­hydroxy praziqu-
antel (cis-­4 -­O H-­PZQ and trans-­4 -­O H-­PZQ) which have some
antiparasitic properties (Meister et al., 2014; Tubbs, Mathieson,
& Tingle, 2008). A proportion of the drug is excreted in the na-
tive form while other metabolites are excreted via the kidneys
(Björklund & Bylund, 1987). Relatively few studies have addressed
the pharmacokinetics of topical praziquantel; however, it appears
that the drug is also distributed in the muscle and plasma follow-
ing administration. There is evidence that praziquantel adminis-
tered in the water is mainly absorbed through the gills, with small
amounts absorbed through the skin before being spread through-
out the rest of the body (Kim, Kim et al., 2001). In marine fish,
praziquantel may be ingested in water.
In the case of using praziquantel in fish intended for human food,
an understanding of pharmacokinetics is also important for estab-
lishment of proper withdrawal times. Currently, there is no resi-
due limit specified for praziquantel in fish marketed for food, and
therefore, no detectable quantity of praziquantel would be toler-
ated. Since there is no recommended treatment regimen for using
praziquantel in fish, there has not been consistency in the dosing
and methods of administration when testing for tissue residues in
fish (Table 4).
The majority of residue studies focusing on oral delivery ad-
ministered doses ranging from 10 to 500 mg/kg. There is evidence
that the rate of metabolism and prevalence in fish may be depen-
dent on host species and environmental conditions (e.g., stocking
density, salt concentration, water temperature). For instance, for
Pacific bluefin tuna that were fed 15 mg/kg praziquantel in treated
feed, praziquantel was below detectable levels (0.2 μg/g) within
24 hr (Ishimaru et al., 2013) while grass carp that were kept either in
brackish water or freshwater still had detectable levels (0.05 μg/ml)
of praziquantel at 96 hr post-treatment when they were only given
10 mg/kg (Xie, Zhao, Yang, & Hu, 2015). Grass carp that were kept in
freshwater also achieved higher praziquantel concentrations in the
plasma, muscle, liver, and kidney when compared to those treated in
brackish water. While many studies did not establish the time point
for complete praziquantel elimination in hosts, a 400 mg/kg oral
treatment given for 3 days to rockfish, which is a much larger treat-
ment needed for most parasites removal, was completely eliminated
within 168 hr (7 days). This suggests that even large oral treatments
need only a short withdrawal period.
Only a single praziquantel dip treatment has been examined
for pharmacokinetics. In this study, rockfish were placed into a
100 mg/L bath treatment for 4 min followed by determination of
praziquantel in plasma and muscle samples. Maximum concentra-
tions were achieved in the plasma at 12 hr and were undetectable by
96 hr post-treatment. Maximum concentrations in the muscle were
achieved at 3 hr and were undetectable by 48 hr post-treatment
(Kim, Kim et al., 2001).
The pharmacokinetics and tissue residues associated with inject-
able praziquantel are understudied in fish. There is evidence that
an injectable treatment can eliminate digenean trematodes (Lorio,
1989); however, no studies have utilized injectable treatments for
monogenean or cestode parasites. While the assumption is that in-
jectable praziquantel is a rational choice for platyhelminthes found
BADER et al. |
      147

TA B L E   4   Studies on the pharmacokinetics of praziquantel in fish. Cmax is the maximum concentration found in the given tissue

Elimination
Host Route Dose Tissue Cmax Tmax (h) T1/2 (h) time (h) Paper

Grass carp—brackish water Intubation 10 mg/kg Plasma 0.76 μg/g 0.5 1.85 Present at 96 Xie et al.
(2015)
Grass carp—brackish water Intubation 10 mg/kg Muscle 0.51 μg/g 1 1.12 Present at 96 Xie et al.
(2015)
Grass carp—brackish water Intubation 10 mg/kg Liver 2.70 μg/g 0.5 2.69 Present at 96 Xie et al.
(2015)
Grass carp—brackish water Intubation 10 mg/kg Kidney 2.99 μg/g 1 2.87 Present at 96 Xie et al.
(2015)
Grass carp—freshwater Intubation 10 mg/kg Plasma 0.91 μg/g 0.5 3.25 Present at 96 Xie et al.
(2015)
Grass carp—freshwater Intubation 10 mg/kg Muscle 0.62 μg/g 0.5 0.31 Present at 96 Xie et al.
(2015)
Grass carp—freshwater Intubation 10 mg/kg Liver 3.87 μg/g 0.5 0.35 Present at 96 Xie et al.
(2015)
Grass carp—freshwater Intubation 10 mg/kg Kidney 3.39 μg/g 1 0.76 Present at 96 Xie et al.
(2015)
Pacific Bluefin Tuna Feed 15 mg/kg Serum 2.0 μg/ml 1.5 24 Ishimaru
single dose et al.
(2013)
Pacific Bluefin Tuna Feed 15 mg/kg Muscle 1.6 μg/ml 0.5 24 Ishimaru
single dose et al.
(2013)
Pacific Bluefin Tuna Feed 15 mg/kg Liver 10.2 μg/ml 0.5 24 Ishimaru
single dose et al.
(2013)
Pacific Bluefin Tuna Feed 15 mg/kg Kidney 3.8 μg/ml 1.5 24 Ishimaru
single dose et al.
(2013)
Rainbow trout Intubation 500 mg/kg Serum 10.6 μg/g 4 Present at 32 Björklund
and
Bylund
(1987)
Rainbow trout Intubation 500 mg/kg Bile 16.1 μg/g 8 Present at 32 Björklund
fluid and
Bylund
(1987)
Rainbow trout Intubation 500 mg/kg Liver 31.8 μg/g 4 Present at 32 Björklund
and
Bylund
(1987)
Rainbow trout Intubation 500 mg/kg Muscle 10.2 μg/g 8 Present at 32 Björklund
and
Bylund
(1987)
Rainbow trout Intubation 50 mg/kg Liver 0.416 μg/g Present at 120 Soukupova-­
Markova
et al.
(2015)
Rainbow trout Intubation 50 mg/kg Plasma 22 ng/ml Present at 48 Soukupova-­
Markova
et al.
(2015)

(Continues)
 |
148       BADER et al.

TA B L E   4   (Continued)

Elimination
Host Route Dose Tissue Cmax Tmax (h) T1/2 (h) time (h) Paper

Rainbow trout Intubation 50 mg/kg Muscle 3.49 μg/kg Present at 816 Soukupova-­

Markova
et al.
(2015)
Rice Eel Intubation 10 mg/kg Plasma 361 μg/μg 5.36 Present at 48 Xu, Dong,
Yang, and
Ai (2016)
Rice Eel Intravenously 5 mg/kg Plasma 17.1 Xu et al.
(2016)
Rockfish Dip 100 mg/L for Plasma 5.96 μg/L 12 96 Kim et al.
4 min (2001)
Rockfish Dip 100 mg/L for Muscle 0.49 ug/L 3 48 (Kim et al.,
4 min 2001)
Rockfish Feed 200 mg/kg for Muscle 48 Kim et al.
3 days (2003)
Rockfish Feed 200 mg/kg for Skin 96 Kim et al.
3 days (2003)
Rockfish Feed 400 mg/kg for Muscle 144 Kim et al.
3 days (2003)
Rockfish Feed 400 mg/kg for Skin 168 Kim et al.
3 days (2003)
Rockfish Intubation 100 mg/kg Plasma At 24 hr Present at 24 Kim and
~3.2 μg/ml Kim (2002)
Rockfish Intubation 200 mg/kg Plasma At 24 hr Present at 24 Kim and
~7.2 μg/ml Kim (2002)
Rockfish Intubation 400 mg/kg Plasma 8.59 μg/ml 9 120 Kim et al.
(2001)
Rockfish Intubation 400 mg/kg Muscle 4.20 μg/g 9 120 Kim et al.
(2001)
Yellowtail amberjack Intravenously 40 mg/kg Plasma 20.30 μg/ml 0.5 8.57 Present at 24 Tubbs and
Tingle
(2006)
Yellowtail amberjack Intravenously 40 mg/kg Skin 8.70 μg/ml 1.5 7.23 Present at 24 Tubbs and
Tingle
(2006)
Yellowtail amberjack Intubation 40 mg/kg Plasma 12.73 μg/ml 1.0 6.57 Present at 24 Tubbs and
Tingle
(2006)
Yellowtail amberjack Intubation 40 mg/kg Plasma 10.62 μg/ml 6 7.91 Present at 24 Tubbs and
Tingle
(2006)
Yellowtail amberjack Intubation 40 mg/kg Skin 5.26 μg/ml 1.5 5.78 Present at 24 Tubbs and
Tingle
(2006)
Yellowtail amberjack Intubation 40 mg/kg Skin 3.96 μg/ml 6 4.72 Present at 24 Tubbs and
Tingle
(2006)

Tmax is the amount of time it took for the maximum concentration to be reached in the host tissue. T1/2 represents the elimination half-­life of praziqu-
antel in the given tissue. Elimination time (h) represents the total amount of time from the administration of praziquantel until levels were no longer
detectable in the host tissue. Blank boxes represent parameters that could not be determined for a given study.
BADER et al.
in tissues, only a single study examined the effects of a 40 mg/kg
intravenously administered praziquantel injection in yellowtail am-
berjack (Tubbs & Tingle, 2006). In this study, praziquantel was still
present in the skin and plasma after 24 hr.
Future residue studies should examine maximal doses that
have been shown to be effective against parasites. Treatment for
monogeneans may require bath treatments up to 10 mg/L for 48 hr
(Forwood, Harris, & Deveney, 2013a,b), while injectable and oral
treatments require up to 25 mg/kg and 200 mg/kg single dose, re-
spectively (Kim et al., 1998; Lorio, 1989). It appears that praziquan-
tel is quickly eliminated from the host tissues. When rockfish were
administered 400 mg/kg orally for 3 days, there were no detect-
able limits of praziquantel after 168 hr (7 days) (Kim et al., 2003).
However, studies examining individual species of fish should be
consulted when determining withdrawal times. In addition, studies
reporting tissue elimination should provide the limit of detection for
their assay, which is often not provided.
7 | TOX I C IT Y
In general, praziquantel has a wide margin of safety with relatively few
side effects in mammals. Some studies have demonstrated adverse
physical reactions to the use of praziquantel treatment in fish. For ex-
ample, silver carp exposed to a 100 mg/L bath treatment for 18 min
swam upside-­down and erratically. These fish were then moved to
freshwater and were able to recover after 30 min without any last-
ing detrimental effects (Szekely & Molnar, 1991). Bath treatments
have varying levels of toxicity based on the species being treated.
When golden shiners and grass carp were treated with high doses
of praziquantel, mortality events were observed with concentrations
of 50–65 mg/L (Mitchell & Hobbs, 2007). It is unclear why some fish
species may be more susceptible to toxic effects of praziquantel.
Studies revealing the mechanism of this toxicosis are needed. In any
case, practitioners should exercise caution when using praziquantel
in new fish host species. There have not been any toxic effects re-
ported in fish that have been fed or intubated with large doses of
praziquantel. The largest dose that has been studied was a single
500 mg/kg dose administered to rainbow trout orally, and in this
case, no adverse effects were observed (Björklund & Bylund, 1987).
Efficacy studies have revealed that the highest doses needed to kill
relatively resilient monogeneans were 40 mg/L, but this concen-
tration can be reduced by extending the treatment time (Forwood,
Harris, & Deveney, 2013a,b). Therefore, it appears that the doses
relevant to treatment are much lower than those needed to cause
side effects. It is unknown whether there are any fish species with
increased susceptibility to adverse reactions caused by praziquantel.
8 | E N V I RO N M E NTA L CO N C E R N S
There have been relatively few studies addressing the fate of prazi-
quantel in the environment (Bártíková, Podlipná, & Skálová, 2016).
|
      149
However, there is a general concern that anthelmintics present in
small quantities can lead to resistance, (Chaiworaporn et al., 2005;
Köhler, 2001; Yoshimura & Endoh, 2005) or destruction of other or-
ganisms in aquatic environments (Morley, 2009). The main concern
of environmental praziquantel contamination is unintentional killing
of free-­living non-­parasitic flatworms. Free-­living flatworms have
also shown to indirectly influence macro-­and meiofauna (Majdi,
Bioche, Traunspurger, & Lecerf, 2013), potentially changing food
webs if removed. When Dugesia japonica was subjected to 70 μM
praziquantel for 48 hr, it was discovered that praziquantel caused
bipolar regeneration, creating a second head on the opposite end
of the body when damaged. Even though orally treated fish can ex-
crete active praziquantel (Björklund & Bylund, 1987), it is unclear if
concentrations relevant to environmental disturbance are produced.
While the environmental concentrations are likely dependent upon
dose and stocking density, there have not been examples of high
concentrations of praziquantel being discharged into the environ-
ment after a treatment regimen.
A limited number of trials have been performed to observe the
effects of praziquantel on arthropods and plants. Dung beetles ex-
posed to praziquantel may experience changes in coloration; how-
ever, the LD50 for this species is greater than 1,000 mg/kg (Hempel
et al., 2006). Interestingly, doses as low as 25 mg/kg are adequate for
eliminating metacestodes inside dung beetles (Dhakal et al., 2015).
The common reed (Phragmites australis) has not only been shown to
have no adverse reactions to all doses studied, but has also shown
to have the ability to metabolize praziquantel, providing a means of
phytoremediation (Marsik, Podlipna, & Vanek, 2016).
Selection for drug-­resistant parasites is a concern; however, there
are relatively few reports of praziquantel-­resistant parasites. In the
case of Schistosoma, there have been reports of praziquantel resis-
tance associated with mass drug administration in human patients
(Ismail et al., 1999; King, Muchiri, & Ouma, 2000). In aquaculture
systems, disposal of praziquantel could be problematic if resistance
can arise as a result of exposure to subtherapeutic doses (Köhler,
2001). Residual praziquantel may be present in water used for dip
or bath treatments, and fish given oral or parenteral praziquantel
may excrete the drug into the water for up to 36 hr post-treatment
(Björklund & Bylund, 1987). Operators may be able to use UV pho-
tocatalytic degradation to eliminate praziquantel; however, it is not
clear whether this is necessary or practical. (Havlíková, Šatínský,
& Solich, 2016). In marine environments, bacteria may metabolize
praziquantel thereby eliminating it from a system (Thomas, Dawson,
Helen, & Andrew, 2016). Going forward, there is a need to inves-
tigate the fate of praziquantel in aquaculture systems in order to
more accurately assess concerns about resistance or environmental
contamination.
9 | CO N C LU S I O N
Culture of fish for food and ornamental purposes continues to grow
in popularity, and it is important for veterinarians to be involved in
 150       | BADER et al.

the medical care of these species. Many therapeutic techniques and

1 host at 1 dosage (yellowtail amberjack,

100 mg/kg 200 mg/kg 400 mg/kg, and

treatments developed and used in mammals require validation be-

pacific Bluefin tuna 15 mg/kg, rainbow

5 hosts at 9 doses (grass carp 10 mg/kg,
1 host at 1 dosage (Rockfish, 100 mg/L

trout 500 mg/kg, rockfish 200 mg/kg

fore they can be considered safe and effective in aquatic species.

for 3 days 400 mg/kg for 3 days

yellowtail amberjack 40 mg/kg)

Fish, like other vertebrates, suffer production issues of health,
welfare, and feed efficiency when infected with helminth parasites.
Both larval and adult forms of cestodes and trematodes parasitize
fish and in some instances pose a threat to human health. However,
Pharmacokinetics

relatively few therapeutic options are available for removal of plat-

yhelminthes in fish. Praziquantel is an anthelmintic effective for

40 mg/kg)
for 4 min)
treating flatworm infections and has broad applications in human
and veterinary medicine. In general, praziquantel is effective for

Dip treatments are considered any bath treatment lasting 3 hr or less. Boxes that are left blank represent treatment strategies that currently have no data present.
treatment of cestodes and trematodes in fish. Both ectoparasitic
monogeneans and endoparasites infecting fish are effectively re-
red shiner, and red snapper)

huronensis, Bothriocephalus

(Common carp, grass carp,

(Bonytail chub, grass carp,

3 species (Atractolytocestus
moved with treatment, but the amount of time necessary for total
acheilognathi, and Khawia
1 species (Bothriocephalus
acheilognathi) in 4 hosts

elimination of praziquantel from the host is unknown for most treat-

sinensis) in 3 hosts
ment regimens. Praziquantel has shown to have very low levels of
and turbot) toxicity in fish, requiring a 100 mg/L bath treatment or oral doses
above 500 mg/kg before negative effects are noted in most species.
Cestode

Further research is needed to understand the toxic effects observed

in some species, and caution should be used when considering the
use of praziquantel in a new host species. Although disposal of prazi-
Clinostomum marginatum, and Diplostomum

channel catfish, grass carp, and silver carp)

opisthorchis, and Diplostomum spathaceum)

quantel does not appear to pose dangerous environmental concerns,

in 2 hosts (Pacific Bluefin Tuna and Grass
Posthodiplostomum minimum) in 2 hosts
1 species (Diplostomum spathaceum) in 2

2 species (Clinostomum marginatum and

spathaceum) in 4 hosts (sunshine bass,

additional studies are needed to determine preferred methods for

3 species (Clinostomum complanatum,

3 species (Cardicola forsteri, Cardicola

disposal of water containing the drug. Future studies should ad-

hosts (grass carp and silver carp)
TA B L E   5   Summary of parasitic species and hosts that praziquantel has been tested on in aquaculture

dress the elimination of larval cestodes and trematodes, especially

(channel catfish and bluegill)

in the context of human health. Additionally, there are still multiple

treatment methods that have not been attempted (Table 5). There is
currently no data available on the effects of injectable praziquantel
on monogeneans, dip or injectable treatments on cestodes, or the
pharmacokinetics of bath treatments in the host fish.
Digenean

One challenge in the area of drug efficacy studies for parasites of

Carp)

fish is the ability to conduct and compare standardized experimental

protocols in different laboratories given the broad range of parasites
Gyrodactylus aculeati, Gyrodactylus turnbulli, Haliotrema abaddon,

and hosts. For example, biochemical assays detecting parasite death

and Zeuxapta seriolae) in 5 hosts (Yellowtail amberjack, Takifugu
Lepidotrema bidyana, Microcotyle sebastis, Neobenedenia girellae,
guppy, stickleback, West Australian dhufish, and silver perch)
amberjack, Black crappie, White-­spotted eagle rays, goldfish,

are preferable to subjective assessments of motility. According to the

Lepidotrema bidyanain) 9 hosts (European catfish, Yellowtail

2 species (Benedenia seriolae and Gyrodactylus sp.) in 2 hosts

VICH-­specific recommendations for assessing anthelmintics in other

9 species (Ancylodiscoides vistulensis, Benedenia seriolae,
Cleidodiscus sp., Clemacotyle australis, Dactylogyrus sp.,

species, at least six animals per experimental group are preferred. A

6 species (Benedenia seriolae, Heterobothrium okamoti,

particular challenge is the ability to complete the life cycle for many
of the parasites, especially the digeneans and the cestodes. For these
parasites, it may be necessary to use naturally infected animals. Such
rubripes, silver perch, chub mackerel)

studies may be necessary but should be approached with caution

(Cownose rays and Rainbow Trout)

since all individuals do not have the same starting parasite abun-
dance. On the other hand, for monogeneans, experimental infections
may be possible and thereby preferred. Investigators should differ-
entiate between prevalence (the number of animals infected) and the
abundance (number of parasites per host) when reporting results.
It is unclear if a praziquantel product will become labeled for fish
Monogenean

in the United States. Many of the studies cited in this review pro-
vide initial evidence for praziquantel use in fish; however, studies
necessary for product approval are often much more involved. In
the future, VICH guidance for anthelmintic assessment in fish could
Inject

be a useful tool. Unfortunately, such guidelines may be somewhat

Bath

Oral
Dip

difficult to form due to the breadth of fish and parasite species. In

BADER et al.
the future, prioritization of specific fish hosts and parasites would be
beneficial in order for investigators to focus their efforts. Refining
methods for detection of parasite death and identification of specific
priority pathogens in the aquaculture community would be benefi-
cial for steering future studies of praziquantel in fish.
C O N FL I C T O F I N T E R E S T
The authors have no conflicts to declare.
AU T H O R C O N T R I B U T I O N S
CB, DS, DJ, and MB conceived the study. CB conducted the litera-
ture and drafted the manuscript. All authors revised and approved
the final manuscript.
ORCID
Matthew T. Brewer  http://orcid.org/0000-0001-7538-1934
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How to cite this article: Bader C, Starling DE, Jones DE,
Brewer MT. Use of praziquantel to control platyhelminth
parasites of fish. J vet Pharmacol Therap. 2019;42:139–153.
https://doi.org/10.1111/jvp.12735