Consumption of drugs for sea lice infestations in Norwegian fish farms: Methods for assessment of treatment patterns and treatment rate

Abstract

Sea lice are a major problem in Norwegian fish farms; however, data on drug treatment patterns or treatment rates of sea lice infestations are not available. Such data are important for analysing resistance patterns against drugs used for such infestations. The main objective of the present study was to develop a method to estimate the treatment patterns and treatment rates for drugs used in the treatment against sea lice (Lepeophtheirus salmonis and Caligus elongatus) in farm salmonids by means of national sales statistics. Annual sales figures, as weight of active substances, were obtained from the drug wholesalers and the feed mills. The weight of active drug substances is not useful as a unit of measurement of drug use in an epidemiological context because it does not correct for dosage differences and number of repeat treatments. To correct for these factors, we introduced approved daily dose (ADD(farm fish)) and treatment course-doses(farm fish) kg(-1) live-weight fish. To express the drug treatment patterns, the biomass (in weight) of farm salmonids treated with 1 course of a drug were estimated. When measured as kg active substance, the quantities of drugs for the treatment of sea lice infestations declined by 98% during the study period (1989 to 2002) but this figure increased 5-fold when it was corrected for differences in dosage. To correct for amounts of farm salmonids liable to require treatment we estimated the annual treatment rate, defined as the number of treatments for sea lice infestations per biomass slaughtered Atlantic salmon Salmo salar and rainbow trout Oncorhynchus mykiss. The annual treatment rate increased gradually during the study period; however, it varied considerably (range 0.45 to 1.34, mean 0.90). Before 1995, organophosphates were the most frequently used drugs against sea lice; since then pyrethroids have become the dominating drug group.

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DISEASES OF AQUATIC ORGANISMS
Dis Aquat Org
Vol. 60: 123–131, 2004 Published August 9
INTRODUCTION
Sea lice (Lepeophtheirus salmonis, also referred to
as ‘the salmon louse’, and Caligus elongatus) are
marine ectoparasitic copepods (Copepoda: Caligidae)
on salmonid fishes. These parasites cause severe prob-
lems in the marine aquaculture of salmonids such as
Atlantic salmon Salmo salar and rainbow trout Oncor-
hynchus mykiss in Northern Europe and on both coasts
of North America. The parasites undergo 10 develop-
mental stages during their life period, each separated
by a moult. The first 2 stages are planktonic, while the
third, the copepodite, attaches to the fish. The next 4
stages (chalimus) are attached to the fish-host by a pro-
tein filament, while the last 3 (pre-adults and adult)
can move freely on the surface of the host. These are
often referred to as ‘mobiles’ and are the stages that
cause problems for the host. Heavy sea lice infestations
may cause primary (e.g. high levels of the stress hor-
mone cortisol), secondary (e.g. osmoregulatory prob-
© Inter-Research 2004 · www.int-res.com
*Email: kari.grave@veths.no
Consumption of drugs for sea lice infestations in
Norwegian fish farms: methods for assessment of
treatment patterns and treatment rate
K. Grave
1,
*
, T. E. Horsberg
1
, B. T. Lunestad
2
, I. Litleskare
3
1
Department of Pharmacology, Microbiology and Food Hygiene, Norwegian School of Veterinary Science,
PO Box 8146 Dep., 0033 Oslo, Norway
2
National Institute of Nutrition and Seafood Research, PO Box 176 Sentrum, 5804 Bergen, Norway
3
WHO Collaborating Centre for Drug Statistics Methodology, Norwegian Institute of Public Health, PO Box 4404 Nydalen,
0462 Oslo, Norway
ABSTRACT: Sea lice are a major problem in Norwegian fish farms; however, data on drug treatment
patterns or treatment rates of sea lice infestations are not available. Such data are important for
analysing resistance patterns against drugs used for such infestations. The main objective of the pre-
sent study was to develop a method to estimate the treatment patterns and treatment rates for drugs
used in the treatment against sea lice (Lepeophtheirus salmonis and Caligus elongatus) in farm
salmonids by means of national sales statistics. Annual sales figures, as weight of active substances,
were obtained from the drug wholesalers and the feed mills. The weight of active drug substances is
not useful as a unit of measurement of drug use in an epidemiological context because it does not cor-
rect for dosage differences and number of repeat treatments. To correct for these factors, we intro-
duced approved daily dose (ADD
farm fish
) and treatment course-doses
farm fish
kg
–1
live-weight fish. To
express the drug treatment patterns, the biomass (in weight) of farm salmonids treated with 1 course
of a drug were estimated. When measured as kg active substance, the quantities of drugs for the
treatment of sea lice infestations declined by 98% during the study period (1989 to 2002) but this
figure increased 5-fold when it was corrected for differences in dosage. To correct for amounts of
farm salmonids liable to require treatment we estimated the annual treatment rate, defined as the
number of treatments for sea lice infestations per biomass slaughtered Atlantic salmon Salmo salar
and rainbow trout Oncorhynchus mykiss. The annual treatment rate increased gradually during
the study period; however, it varied considerably (range 0.45 to 1.34, mean 0.90). Before 1995,
organophosphates were the most frequently used drugs against sea lice; since then pyrethroids have
become the dominating drug group.
KEY WORDS: Sea lice · Drug use · Course-dose · Treatment patterns · Treatment rates
Resale or republication not permitted without written consent of the publisher

Dis Aquat Org 60: 123–131, 2004
lems) and tertiary (e.g. increased disease incidence)
stress responses in salmonids (Grimnes & Jakobsen
1996, Bowers et al. 2000, Finstad et al. 2000, Mustafa
et al. 2000). Infestation is controlled by management
strategies (e.g. separation of year classes) and drug
treatment.
Although sea lice infestations are a major problem in
Norwegian fish farms, data on drug treatment patterns
or on the treatment rates of sea lice infestations are not
available. Such data are important for analysing resis-
tance patterns against drugs used for the treatment of
sea lice infestations. However, data on the consump-
tion (as weight of active substance) of drugs used for
sea lice infestations in Norway have been recorded
and have been publicly available since 1981 (Grave et
al. 1991). Because drugs formulated for use against sea
lice infestations in farm salmonids are highly species-
specific, national sales data of this drug group are
thought to be a good estimate of the quantities used in
this group. But weight of active substance as a unit of
measurement does not take into account differences in
the dose (differences in potency and bioavailability
etc.) used for the various drug substances. This unit is
therefore not useful when analysing and interpreting
drug sales statistics in an epidemiological context, e.g.
to estimate treatment patterns. Furthermore, to esti-
mate the treatment rates of salmon lice infections, the
population of farm salmonids liable to require treat-
ment has to be considered. The main objective of this
study was to develop a method to estimate treatment
patterns and treatment rates of drugs used against sea
lice infestations in farm fishes for human consumption,
by use of national sales statistics.
MATERIALS AND METHODS
Data sources. All drugs used for the treatment of
farm fishes in Norway are prescription drugs. In addi-
tion to the preparations approved in Norway, veteri-
nary surgeons may apply for authorisation to use drugs
on farm fishes for which no marketing authorisation
has been granted. All veterinary drugs have to be dis-
pensed through pharmacies supplied solely by autho-
rised drug wholesalers. An exemption is made for
medicated feed for therapeutic use that is produced
and dispensed by approved feed mills in accordance
with EU directive 90/167/EEC.
Until 1999, overall sales data from the Norwegian
drug wholesalers and feed mills dispensing medicated
feed for therapeutic use in farm fishes were collected
by the state-owned drug wholesaler Norwegian Medi-
cinal Depot AS (NMD). From 1 January 2000, it has
been mandatory for the drug wholesalers and feed
mills dispensing medicated feed to report annual sales
figures to the Norwegian Institute of Public Health
(NIPH). The annual sales figures, as kg active sub-
stance, for drugs used for sea lice infestations were
provided for 1989 to 1999 by NMD, and for 2000 to
2002 by NIPH. The figures also include medicinal
products exempted from market authorisation that are
stocked on a regular basis by the drug wholesalers.
For the year 1999, the sales data presented are incom-
plete because 1 wholesaler did not report all data (I.
Litelskare unpubl. data). Because overall sales figures
of drugs from the wholesalers and the feed mills
roughly represent the quantities used of these drugs,
the terms ‘consumption’ and ‘usage’ will be considered
synonymous with ‘sales figures’ in this paper.
Drug classification system. In Norway, the Anatom-
ical Therapeutic Chemical veterinary (ATCvet) classi-
fication system is used to classify veterinary medicinal
products (WHO 2003a). The data presented in this
study are classified according to the ATCvet classifica-
tion system.
Units of measurement for drug use. In human medi-
cine, defined daily doses (DDDs) are assigned by the
WHO International Working Group for Drug Statistics
Methodology (WHO 2003b) and the established DDDs
are a consensus based on dosages approved in various
countries. The DDD is used as a unit of measurement
in drug-consumption studies, allowing comparison of
drug use in a medical context, and also between
periods, regions and countries (Capellà 1993, WHO
2003b). For drugs used on a short-term basis, the total
treatment course dose (hereafter ‘course-dose’) may be
used as unit of measurement (WHO 2003b).
Official DDDs have not been assigned for veterinary
drugs. Therefore, in order to facilitate comparison
of annual treatment patterns and treatment rates of
drugs used for sea lice infestations we introduced
approved daily dose (ADD
farm fish
) and treatment course-
doses
farm fish
(in mg active substance) as a measurement
unit for this group of drugs. The ADD
farm fish
and course-
doses
farm fish
are expressed per kg live-weight and are
estimated on the basis of the approved dosages pub-
lished by the Norwegian Compendium of Veterinary
Medicines (Tørisen 1988–2002). These are ‘pocket for-
mularies’ used by veterinary surgeons in their every-
day practice, and contain the approved dosage recom-
mendations for all pharmaceutical specialties with
marketing authorisation in Norway. For drugs under
exemption from market authorisation, we took the
approved dosages given on the relevant package
leaflets. The ADD
farm fish
and the course-dose
farm fish
are
thought to be close to the actual daily doses and
course-doses used in practice. For drugs with a tem-
perature-dependent dosage regimen, we selected the
average of the dosage regimen representing a temper-
ature range of 5 to 15
o
C as the ADDs
farm fish
.
124

Grave et al.: Drug use against sea lice
Drugs used for sea lice infestation are either admin-
istered orally in the feed (over 7 to 14 d) or topically as
a bath treatment. Some of the drugs administered as
bath treatment have to be applied twice at 2 to 3 wk
intervals to achieve optimal efficacy. For the orally
administered drugs (QP53BC, QP54AA), we obtained
the ADDs and the course-doses directly from the Nor-
wegian Compendium of Veterinary Medicines. For
the bath treatments (QP53AC, QP53AF) it was antici-
pated that 1 m
3
of delousing solution would be
enough for a single bath treatment of 50 kg fish
(0.02 m
3
kg
–1
). The ADD
farm fish
kg
–1
live-weight was
estimated as the amount of drug (mg) recommended
for 0.02 m
3
prepared delousing solution (Tørisen
1988–2002). The course-doses
farm fish
were set by mul-
tiplying the ADDs
farm fish
by the recommended number
of repeated treatments per course for the relevant
drug (Table 1).
Treatment patterns. The drug sales statistics (pro-
vided by NMD and NIPH) are expressed as kg active
substance. The overall biomass (kg) of farm fishes
treated annually with 1 course of a drug for sea lice
infestations was estimated using the following formula:
Annual treatment rate. Because data on numbers of
individuals liable to require treatment are not avail-
able, the biomass (kg) of salmonids slaughtered annu-
ally, was defined as the population liable to require
treatment for sea lice infestations. The annual treat-
ment rate was defined as the calculated numbers of
treatments for sea lice infestations per tonne Atlantic
salmon and rainbow trout slaughtered each year
(cumulative treatment rate). Data on the annual bio-
mass of farm Atlantic salmon and rainbow trout
slaughtered (for sale) for the years 1989 to 2000
were obtained from Statistics Norway (available at
www.ssb.no 26 April 2004). The corresponding data for
2001 and 2002 were obtained from the Directorate of
Fisheries (www.fiskeridir.no/sider/statistikk/opdrett/
mat_historie.xls 26 April 2004). The figures for 1991
have not been published since they were con-
sidered unreliable (www.ssb.no/aarbok/1996/tabeller/
t351.html 26 April 2004).
Number of fishes treated annually. The estimated
weight of farm Atlantic salmon and rainbow trout
treated against sea lice does not give any information
on the numbers treated (i.e. population liable to
require treatment). In order to support the control of
pharmaceutical residues in fish products, a national
surveillance programme was established in Norway in
January 1989 (Bangen et al. 1994). This programme
requires that copies of all prescriptions for drugs
intended for use on farm fishes be sent to the Direc-
torate of Fisheries (DF), both by the prescribing veteri-
nary surgeons and by the dispensing pharmacies and
feed mills. Moreover, veterinary surgeons are obliged
to fill out an authorised prescription form supplying
fish-farm identity and locality, type and amount of the
kg farm fishes treated
Amount (mg) of drug sold yr
Course- dose (mg) kg farm fish
–1
–1
=
125
Table 1. Dosage regimens, estimated ADDs
farm fish
(approved daily dosage) and course-doses
farm fish
for drugs used for the
treatment of sea lice (Lepeophtheirus salmonis and Caligus elongates) infestations in farmed Atlantic salmon Salmon salar and
rainbow trout Onchorynchus mykiss in Norwegian fish farms (Tørisen 1988–2002). ATCvet code: Anatomical Therapeutic
Chemical veterinary classification system
Drug group/ Active Recommended dosage Estimated Recommended Estimated course-
ATCvet code substance per treatment (route of ADD
farm fish
no. of dose
farm fish
administration) (mg kg
–1
)treatments (mg kg
–1
)
Pyrethrins and pyrethroids
QP53AC01 Pyrethrins
a
100 mg m
–3
(bath) 2 1 2
QP53AC08 Cypermethrin 5 mg m
–3
(bath) 0.1 1 0.1
QP53AC08 High-cis cypermethrin 15 mg m
–3
(bath) 0.3 1 0.3
QP53AC11 Deltamethrin 3 mg m
–3
(bath) 0.06 1 0.06
Organophosphorous compounds
QP53AF17 Azamethiphos 100 mg m
–3
(bath) 2 2 4
QP53AF02 Metriphonate 73 000 mg m
–3
(bath) 1460 2 2920
QP53AF04 Dichlorvos 1000 mg m
–3
(bath) 20 2 40
Chitin-synthesis inhibitors
QP53BC02 Diflubenzuron 3 mg kg
–1
(oral) 3 14 d continuous 42
QP53BC03 Teflubenzuron 10 mg kg
–1
(oral) 10 7 d continuous 70
Avermectins
QP54AA06 Emamectin benzoate 0.05 mg kg
–1
(oral) 0.05 7 d continuous 0.35
Other antiseptics and disinfectants
Hydrogen peroxide
a,b
1500 000 mg m
–3
(bath) 30 000 2 60 000
a
No specific dosage regimen recommended, values arbitrarily set;
b
ATCvet code not established

Dis Aquat Org 60: 123–131, 2004
drug prescribed, weight and species of fishes to be
medicated, reason for the treatment (diagnosis), start-
ing date of the treatment and recommended with-
drawal periods. DF routinely computerises this infor-
mation, creating a nationwide database for the status
of drug treatment in Norwegian fish farms.
The average size of farm fishes treated with the dif-
ferent drugs against sea lice were estimated based on
data from DF’s database for the period 2000 to 2002.
These years were selected because the data pro-
gramme used by DF in these years allowed electronic
conversion of the recorded data to a Microsoft
®
Excel
spreadsheet, while a direct conversion was impossi-
ble for the prescription data of the preceding years.
The data covering the period 1989 to 1999 (approx.
1500 prescriptions yr
–1
) would have to be repunched
manually to obtain historical data for the whole
period, and this could not be justified because of the
labour cost.
Data on the average size of the farm fishes for each
drug prescribed were used to estimate the number of
fishes treated, since such data are not available in
DF’s database. The annual numbers of farm salmon
and rainbow trout treated with the different drugs
against sea lice for the years 2000 to 2002 was esti-
mated by
No. of fishes treated per year with Drug X =
RESULTS
Treatment patterns
The annual sales figure for drugs used for the treat-
ment of sea lice infestation in the Norwegian fish-
farming industry during the period 1989 to 2002
declined by 98% when expressed as weight of active
substances (Table 2).
The estimated biomass of farm Atlantic salmon and
rainbow trout treated with 1 course against sea lice
versus biomass slaughtered annually are shown in
Fig. 1. These amounts (excluding 1991 and 1999 for
which insufficient data were available) correlate well
(r
2
= 0.980). The calculated amounts of farm salmonids
treated increased 5 times in the study period; however,
great variation was found. The amount was lowest
in 1993 and peaked in 2000, while in the period 2000 to
2002 a 2% decrease was observed.
In the period 1989 to 1992, only organophosphorous
compounds were used to combat sea lice infestations
in Norwegian fish farming. From 1992, new drugs
against these parasites were introduced, and the treat-
ment patterns of drugs against sea lice gradually
changed. Drugs belonging to the pyrethroid group
were introduced in 1994; 2 yr later the proportion of
farm fishes (biomass) treated with a drug from the
pyrethroid group was on average 58%. In 2002, this
figure was 91%, while for the avermectins the corre-
sponding figure was 9%.
Estimated biomass (kg) of fishes treated with Drug X yr
Average fish weight (kg) treated with Drug X yr
–1
–1
126
Table 2. Sales figures (in kg active substances) of drugs used for the treatment against sea lice (Lepeophtheirus salmonis and Caligus elon-
gates) infestations in farmed Atlantic salmon Salmon salar and rainbow trout Onchorynchus mykiss in Norwegian fish farms. Data are based
on sales from feed mills and drug wholesalers. ATCvet code: Anatomical Therapeutic Chemical veterinary classification system
Drug group/ Active 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999
a
2000 2001 2002
ATCvet code substance
Pyrethrins and pyrethroids
QP53AC01 Pyrethrins 32 26 9 18
QP53AC08 Cypermethrin 23 28 3 <0.1 <0.1
QP53AC08 High-cis cypermethrin 19 73 69 62
QP53AC11 Deltamethrin 19 11 23 19 23
Organophosphorous compounds
QP53AF17 Azamethiphos 389 738 606 315 182 14
QP53AF02 Metriphonate 3300 2408 2144 1946 1779 1227 281 138
QP53AF04 Dichlorvos 3488 3416 3588 3115 2470 1147 395 161 36
Chitin-synthesis inhibitors
QP53BC02 Diflubenzuron 160 361 437 50 12
QP53BC03 Teflubenzuron 610 1510 1334 231 62 28
Avermectins
QP54AA06 Emamectin benzoate 4111220
Total in kg 6788 5824 5732 5061 4249 2795 1440 1707 2268 1975 329 181 128 105
Other antiseptics and disinfectants
Hydrogen peroxide
b,c
710 290 340 160 200
Total in tonnes 710 290 340 160 200
a
Data incomplete for 1999 because 1 wholesaler failed to report all sales;
b
ATCvet code not established;
c
sales figures given in tonnes

Grave et al.: Drug use against sea lice
Estimated annual treatment rate
The estimated treatment rate against sea lice varied
considerably, but increased by 37% from 1989 to 2002
(Fig. 2). The treatment rate was lowest in 1993 and
peaked in 2000 (range 0.45 to 1.34, mean 0.90).
Estimated size and numbers of farm fishes treated
DF’s prescription database contained information on
6530 drug prescriptions for treatment against sea lice
for the years 2000 to 2002. A total of 5244 (80%) of
these prescriptions included information on the size
of the fish to be treated. Of the prescriptions giving
information on fish size, we excluded 161 for farm
Atlantic salmon or rainbow trout weighing >5 kg
(mean weight 6.7 kg; range 5.1 to 15 kg) because
these mainly represented brood stock not intended for
human consumption. The annual average size of the
farm fishes treated against sea lice with the drugs
included were calculated based on data from 5083
prescriptions (Table 3). The figures show that the
average weight of fishes treated with high-cis-cyper-
methrin and deltamethrin varied within a range of
less than 7% from 2000 to 2002 (2.40 to 2.58 kg). The
average weight (mean value) of fishes treated with
emamectin benzoate increased by 33% from 0.35 to
0.52 kg in the same period. The average weight of
fishes treated with the chitin-synthesis inhibitor teflu-
benzuron was approximately the same (1 kg) in 2000
and 2001.
127
Fig. 1. Estimated overall biomass of farm Atlantic salmon
Salmo salar and rainbow trout Oncorhynchus mykiss in Nor-
wegian fish farms treated annually with 1 treatment course
(calculated as mg of Drug X sold yr
–1
/ course-dose (mg) kg
–1
fish) against sea lice (Lepeophtheirus salmonis and Caligus
elongatus) (data for 1999 omitted since incomplete), ex-
pressed as tonnes treated versus tonnes slaughtered (data
for 1991 omitted since unreliable)
Fig. 2. Estimated annual treatment rate of sea lice infestations
(Lepeophtheirus salmonis and Caligus elongates) in farm
Atlantic salmon Salmo salar and rainbow trout Oncorhynchus
mykiss in Norwegian fish farms (sales data for 1999 were
incomplete; data for biomass of farm salmonids for 1991
were unreliable)
Treatment rate
Tonnes

Dis Aquat Org 60: 123–131, 2004
The estimated annual numbers of farm Atlantic
salmon and rainbow trout treated with 1 course against
sea lice during 2000 to 2002 are presented in Fig. 3. The
numbers declined by 11% from 2000 to 2002. Mea-
sured as number of fishes treated with the different
drug groups, the estimated proportion of farm Atlantic
salmon and rainbow trout (in numbers) treated with a
drug belonging to the avermectins was 26% in 2000,
increasing to 34% in 2002. The corresponding figures
for the pyrethroid group were 74 and 66%, respec-
tively. The calculated proportion (in numbers) of farm
fish treated with chitin-synthesis inhibitors was 0.5, 0.1
and 0% in 2000, 2001 and 2002, respectively.
DISCUSSION
Data sources
Several studies have concluded that the data pro-
vided by the wholesalers and the feed mills on the
sales of drugs for the treatment of farm fishes in Nor-
way are nearly identical with the corresponding data
derived from prescriptions (Bangen et al. 1994, Grave
et al. 1999, 2002). Furthermore, of the 6530 prescrip-
tions in DF’s database for drugs indicated for use
against sea lice, all but 3 were for Atlantic salmon or
rainbow trout. Thus, the sales figures included in this
study give reliable data on the consumption of drugs
against sea lice by salmonids in Norwegian fish farms.
The prescription database of the DF contains almost
all prescriptions issued for use on farm fishes in Norway
(Bangen et al. 1994, Grave et al. 2003). On average,
80% of the prescriptions covering the years 2000 to
2002 gave information on fish size. Therefore, the esti-
mated fish sizes used in the present study to calculate
the number of farm fishes treated with the different
drugs are considered representative estimates.
Treatment patterns
The relative use of different agents against sea lice
changed considerably from 1989 to 2002, as evident
from Fig. 1. Until the mid-1990s, almost all treatments
were performed with organophosphates. Metrifonate
(trichlorfon), a weak inhibitor of cholinesterases, was
introduced in 1974 for the treatment of sea lice infesta-
tions in the Norwegian fish-farming industry. In 1986,
the cholinesterase inhibitor dichlorvos was introduced.
Organophosphorous drugs were the drugs of choice
for the treatment of sea lice infestations during the
period 1981 to 1988 also (Grave et al. 1991).
128
Table 3. The annual average size (in kg) of farmed Atlantic salmon Salmon salar and rainbow trout Onchorynchus mykiss in
Norwegian fish farms treated with the various drugs against sea lice (Lepeophtheirus salmonis and Caligus elongates) during
2000–2002. Data were derived from Directorate of Fisheries’ prescription database (N = 5083). ATCvet code: Anatomical
Therapeutic Chemical veterinary classification system. n: number; CI: confidence interval
Drug group/ATCvet code Active substance 2000 2001 2002
kg (95% CI)/n kg (95% CI)/n kg (95% CI)/n
Pyrethrins and pyethroids
QP53AC08 Cypermethrin 1.03 (CI not)/2 – –
QP53AC08 High-cis cypermethrin 2.46 (2.32–2.59)/473 2.55 (2.41–2.690)/372 2.58 (2.46–2.70)/367
QP53AC11 Deltamethrin 2.43 (2.34–2.52)/853 2.56 (2.47–2.65)/769 2.40 (2.31–2.49)/697
Chitin-synthesis inhibitors
QP53BC02 Diflubenzuron 0.3 (CI not)/4 – –
QP53BC03 Teflubenzuron 0.98 (CI not)/5 1.01 (CI not)/5 –
Avermectins
QP54AA06 Emamectin benzoate 0.35 (0.32–0.38)/446 0.35 (0.32–0.38)/520 0.52 (0.46–0.58)/570
Fig. 3. Estimated numbers of farm Atlantic salmon Salmo
salar and rainbow trout Oncorhynchus mykiss treated with
1treatment with different drugs against sea lice (Lepeo-
phtheirus salmonis and Caligus elongates) infestation in
Norwegian fish farms
pyrethrins and pyrethroids
chitin-synthetis inhibitors
avermectins
400
350
300
250
200
150
100
50
0
2000
2001
2002
Numbers (×1000 000)

Grave et al.: Drug use against sea lice
Treatments with drugs of the pyrethrin/pyrethroid
group were introduced in 1990 (Jakobsen & Holm
1990), but no significant use was recorded before 1994.
The first product available was based on pyrethrum, a
mixture of 6 compounds with antiparasitic properties
(pyrethrins), extracted from the plant Chrysanthemum
cinerariaefolium. The proposed application method for
this compound, a surface layer of a pyrethrum-oil mix-
ture in the net-pen, was impracticable, and synthetic
compounds administered as a bath treatment soon
replaced this drug (Hart et al. 1997). In 1996, a cyper-
methrin product with an equal mix of the cis and trans
isomers was introduced. In 1998, a product containing
deltamethrin was introduced, shortening the treatment
time from 60 to 30 min. The original cypermethrin
product was replaced in 1999 by a product containing
a higher proportion of the more effective cis-isomers,
with a recommended treatment time of 30 min. In the
period 1993 to 1997, hydrogen peroxide was used to
some extent, mainly due to development of resistance
against organophosphates in a few areas (Denholm et
al. 2002). A relatively narrow margin of safety com-
bined with a moderate efficacy (Bruno & Raynard
1994, Treasurer & Grant 1997) resulted in a short
lifespan of this product.
In the period 1996 to 2001, chitin-synthesis inhibitors
were used as in-feed compounds, but this group of
drugs did not gain a big share of the market. In 1999,
the avermectin emamectin benzoate was introduced,
also as an in-feed product, and offered an effective
alternative to the labour-intensive bath treatments
(Stone et al. 2000). Emamectin benzoate could initially
only be used on small fish, due to a withdrawal period
of 120 d (independent of temperature). The withdrawal
period (the period between the last day of treatment
and the first day on which the fishes can be harvested)
is a major factor of consideration when choosing a
drug for treatment. A long quarantine period makes it
impossible to slaughter fishes in case of emergencies
(e.g. algal blooms), and is an important factor to con-
sider when choosing a drug for the treatment of fishes
close to market size. In 2002, the withdrawal period
was recalculated on the basis of the maximum residues
limit (MRL-value) for all drugs used in the treatment of
aquatic organisms (Directorate of Fisheries 2003). This
changed the withdrawal period for emamectin ben-
zoate to 175 (
o
C) days (temperature × days). A with-
drawal time of 120 d thus represents a temperature of
1.5
o
C. Because treatments against sea lice are usually
performed at much higher temperatures than 1.5
o
C,
since 2002 the withdrawal period has been substan-
tially lowered for the majority of treatments with
emamectin. Thus, the 33% increase in the weight of
fishes treated with emamectin from 2000 to 2002 is
likely to be a result of this change in the withdrawal
period. However, the predominant treatment for larger
fishes (>1 kg) in 2002 was still pyrethroids, mainly
because of the lower costs of these drugs when treat-
ing fish of larger size, and the possibility of being able
to use these compounds up until 1 wk prior to slaugh-
ter. There was no variation in the average weight of
fish treated with the chitin-synthesis inhibitor
teflubenzuron between 2000 and 2001.
Estimated annual treatment rate
Although considerable fluctuations were found, the
present study has shown an increase in the annual
treatment rate in the period 1989 to 2002 (Fig. 2.)
These variations most probably reflect variations in sea
lice infestation due to climatic variations between dif-
ferent years. Warm and sunny springs tend to boost the
reproduction of sea lice, resulting in greater infesta-
tions than in colder springs. This may have caused
higher numbers of re-infections in some farms and may
explain why the annual treatment rate (actual cumula-
tive treatment rate) peaked in 1996, 2000 and 2002.
There may be several explanations for the observed
increase in the annual treatment rate over the years.
Until the mid-1990s, organophosphorous drugs domi-
nated as sea lice agents. These compounds have a
limited efficacy on the chalimus stages of the parasite,
and are recommended to be used twice within a 14 d
period in order to obtain optimal efficacy (Tørisen
1988–2002). This treatment protocol may not always
have been followed. Bath treatments against sea lice
are labour-intensive procedures, and it is believed that
when using organophosphorous drugs, some fish-
farmers did not comply with the recommendation to
repeat the treatment. Thus, the course-doses
farm fish
for
this drug group may be too high, resulting in an
underestimation of the annual treatment rate for this
drug group. This may explain why the estimated treat-
ment rate was substantially lower for the period 1989 to
1995 (when organophosphates were the dominant
drug group) than for the last part of the study period.
As pyrethroids need only to be applied once to obtain
the same treatment efficacy as organophosphates
(Hart et al. 1997), we do not consider that the course-
doses
farm fish
set for this drug group are confounded by
non-compliance. The course-doses in the present
study for pyrethroids are thought to be good estimates.
Another factor contributing to an increase in the
annual treatment rate in the last part of the study
period was a tendency by farmers during this period to
initiate treatments at lower numbers of sea lice per
fish. In 1997, a national programme for the control of
sea lice was introduced in Norway. The main purpose
was to keep the number of parasites as low as possible
129

Dis Aquat Org 60: 123–131, 2004
in the spring, when wild salmon smolts from the rivers
head for the sea and pass through the farming areas. In
the period 1997 to 1999, this programme was organ-
ised on a regional basis, while from 2000 onwards it
was organised on a national level. From 2000 onwards,
the maximum number of Lepeophtheirus salmonis
allowed on each fish during the migration period of
wild salmon smolts was 0.5 adult females, or 5 mobiles
(sum of all post-chalimus stages). Sea lice numbers
were recorded twice a month, and if a higher average
number was found, a drug treatment was mandatory;
non-compliance with these recommendations could
result in considerable fines (Ministry of Agriculture
2000).
Lastly, the introduction of effective oral products
such as emamectin benzoate lowered labour costs sub-
stantially and thus the trigger point for treatment.
Although the biomass of fishes slaughtered each
year does not accurately represent the biomass in the
net-pens throughout the year, it is considered to be a
good estimate. Since farm fishes gain weight continu-
ously until slaughter, the biomass of live individuals in
the net-pens will always be slightly lower than the
slaughtered biomass. Our calculations may therefore
overestimate biomass and thus underestimate treat-
ment rate. Biomass is thought to be a good estimate of
the population liable to require treatment if the aver-
age size of fish treated with a specific drug is stable,
and may enable comparable estimates of the treatment
rate between periods (years). For the period 1989 to
2001, there were no obvious factors (e.g. changes in
withdrawal periods) that would have influenced size of
treated fishes. In the present study, the average weight
of fishes treated with emamectin benzoate increased
by 33% from 2000/2001 to 2002. When the average
size of treated fishes increases, then the number of
individuals that can be treated with a certain quantity
of a drug decreases. Consequently, the population
liable to require treatment measured as the biomass (of
farm fishes) is an overestimate for emamectin benzoate
for 2002 compared with the other years, and the esti-
mated treatment rate for this year is underestimated.
Because emamectin benzoate comprised only a minor
proportion of the treatments in 2002, the underesti-
mate is not of statistical significance.
CONCLUSIONS
When consumption of drugs against sea lice was ex-
pressed as weight of active substances, a 98% de-
crease was observed for the period 1989 to 2002.
However, when expressed as annual treatment rate,
the usage increased by 37% during the study period. It
is concluded that in order to evaluate the prescription
patterns of drugs against salmon lice infestations, it is
crucial to correct for differences in dosages and num-
ber of repeated treatments between the various drug
substances. Although fish biomass does not provide in-
formation about population numbers liable to require
treatment, it was found to be a useful denominator in
estimating annual treatment rate. An exception is
when there are large variations in the average weight
of fishes treated with drugs that are frequently used.
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Editorial responsibility: Otto Kinne,
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Submitted: October 16, 2003; Accepted: March 30, 2004
Proofs received from author(s): June 26, 2004