22.11.

2019

Antiparasitics:

Ectoparasiticides, Endoparasiticides
and Anti-Protozoal Agents
Parasites live at the expense of their hosts
Symbiotes may be
Mutualists -living in mutual benefit with host
Or
Commensals-living without benefit or detriment to host

Parasites may infect

Gastrointestinal tracts or circulatory systems of their hosts,
Invade different tissues and organs
Live on the external surfaces of their hosts.

Many infections may be asymptomatic whereas others may cause

acute (transient) or chronic (persistent) clinical diseases ranging
markedly in severity (mild to fatal).
Category of parasites causing diseases in aquaculture
1. Ectoparasites (live on the outside of a fish host (including the
gills, mouth, skin and fin surfaces))
- Protozoa
- Monogena (Diplectanum sp., Furnestinia sp. and Microcotyle sp.)
-Isopoda/Copepoda (Lernanthropus kroyer)
-Flukes
-Lernea
2. Endoparasites: live in the tissues, blood and/or organs (including
the gastrointestinal tract)
Cestodes
Nematodes
Many types of organisms have adopted a parasitic mode of
existence; that is, they require a host for their own survival.

Three major groups of parasites are recognized:

1. protozoa (belonging to the kingdom Protista), and 2.
helminths and 3. arthropods (belonging to the kingdom
Animalia, or Metazoa).
Antiparasitics are a class of medications which are indicated for the
treatment of parasitic diseases, such as those caused by helminths,
amoeba, ectoparasites, parasitic fungi, and protozoa, among others.

Antiparasitics target the parasitic agents of the infections by

destroying them or inhibiting their growth; they are usually effective
against a limited number of parasites within a particular class.

Antiparasitics may be administered orally, intravenously or topically.

Broad-Spectrum antiparasitics, analogous to broad-spectrum

antibiotics for bacteria, are antiparasitic drugs with efficacy in
treating a wide range of parasitic infections caused by parasites from
different classes
 Anti-protozoal Agents

Parasitic protozoans are responsible for

wide range of diseases in both animals,
man and fish.

These diseases are of world importance

but are difficult to eliminate as they are
frequently transmitted by ticks and fleas
Protozoan disease in fishes are divided in to following categories-
1)Ciliated Protozoans:
Ichthyophthirius multifiliis, Cryptocaryon irritans, Epistylus,
Trichodina, Scyphidia pyriformis, Cyclochosta, Chilodonella etc

2)Flagellated Protozoans: Trypanasoma, Trypanoplasma,

Ichthyobodo (Costia) necator, Bodomonas etc

3)Sporozoans: Myxobolus cerebralis, Myxidium etc

Drugs used for protozoan diseases:

1. Quinapyramine compounds
2. Amicarbalide isethionate
3. Imidocarb dipropionate
4. Quinoronium sulfate
5. Trypan blue
6. Hydroxymethyl quinolones
SYSTEMIC ANTI-PROTOZOAL AGENTS used in fishes
Fumagillin
Fumagillin is an antibiotic produced by the parasitic fungus,
Aspergillus fumigatus, and acts by inhibiting RNA synthesis.

It is acidic and is normally presented as the dicyclohexylamine (DCH)

((C6H11 ) 2NH) salt.
This salt is sparingly soluble in water but moderately soluble in
ethanol.
Fumagillin DCH is heat-labile so it cannot be incorporated in feed
before pelleting.
Fumagillin
The pure drug may be surface-coated onto pellets by dissolving it in
95% ethanol and spraying the solution onto the pellets.
Palatablility is improved by top-coating the medicated pellets with
1:1 mixture of cod liver oil and ethanol.

A 2% premix (Fumidil B®) is available commercially, and this may be

surface-coated onto pellets by conventional methods.
Fumagillin has low antibacterial and anti-fungal activity and is
primarily active against protozoa.
It was formerly used for amoebic dysentery in Man, and Fumidil B is
used against Nosema apis in bees.
In fish medicine fumagillin DCH has been used for:
Microsporea: Enterocytozoon salmonis in chinook salmon
Lorna salmonae in Pacific salmon
Pleistophora anguillarum in eels
Sphaerospora testicularis in sea bass
Sphaerospora renicola in common carp
Myxosporea: Myxosoma (Myxobolus) cerebralis in rainbow trout

It has also been shown to be active in the control of proliferative

kidney disease (PKD), a condition of freshwater salmonids for which
a putative protozoan pathogen has been seen histologically but
never isolated and cultured.
Fumagillin has been tested but found inactive against infections of
Myxobolus cyprini and Thelohanellus nikolskii.
Swim bladder inflammation of common carp
This disease has a complex aetiology but it appears to be initiated by
Sphaerospora renicola.
Molnar et al. (1987) found that in carp infected intraperitoneally, a
diet containing 0.1% fumagillin DCH effectively prevented the
development of disease.
In a natural infection of juvenile carp in a pond the regimen gave
significant but not complete protection.
Symptoms developed but disappeared in a short time and it was
concluded that the fumagillin was more efficacious against the later
stages of the parasite life cycle.
Enterocytozoon salmonis infection
A trial of fumagillin for artificial Enterocytozoon salmonis
infection in chinook salmon has been reported.

The drug was found to prevent proliferation of the parasites

rather than killing them.

The regimen used was 0.1 g/kg fumagillin DCH in a diet fed at
1.5% for 3 weeks starting immediately after the infection
(3mg/kg/day)
Myxosoma cerebralis infection

This parasite is the cause of whirling disease, an economically

important condition of freshwater salmonids, especially rainbow
trout kept in earth ponds.

The nervous symptoms result from lesions produced in the head

cartilages before ossification, and the infection is therefore of
importance only in juvenile fish.

Diet containing 0.1% fumagillin DCH fed at 1% for 4 months

starting 1 month after infection; this is equivalent to 10
mglkg/day.
Sphaerospora testicularis infection

This infection destroys testicular tissue in sea bass and hence

reduces the fecundity of males.

Control has been attempted using Fumidil B® at a rate to give 1

g/kg fumagillin in the feed and feeding at 1.5%, which is 15
mglkg/day, for 8 weeks.

It was found that even at this (relatively high) dose rate the
medication did not affect well-established infections, but it did
advance spermiation by 2 months. As had been found with
Enterocytozoon salmonis infection in chinook salmon at a much
lower dose rate, fumagillin was more parasitistatic then
parasiticidal.
Loma salmonae infection
This disease affects the gills of Pacific salmon in both fresh
and seawater.

The feed medication rate used was 1 g/kg fumagillin DCH, and
feeding was at 1% giving a dose rate of 10 mg/kg/day for 30
days
Pleistophora anguillarum infection
Kano et al. (1982) studied the use of fumagillin DCH in
Japanese eels artificially infected with P. anguillarum.

Following immersion infection, symptoms could be prevented

by immersion in 60.5 ppm fumagillin for 120 hours
Proliferative kidney disease
Hedrick et al. (1988) found fumagillin to be active against
artificial infection with PKD in chinook salmon.

5 mglkg/day for 6 weeks protective;

TARGET SPECIES SAFETY

The safety margin of fumagillin is narrow, at least in salmonids.

In most species studied its main effects are on the

erythropoietic system, including, in some cases, a reduction in
the size of the spleen and kidneys after prolonged treatment.
Nitroimidazoles
Group of synthetic antimicrobial agents active against protozoa
and obligate anaerobic bacteria.
Few drugs of this group are now in use because they give
positive responses to some in vitro mutagenicity tests.

Metronidazole is one which remains in use in human medicine;

and dimetridazole (DMZ) has been used in veterinary medicine
particularly for swine dysentery and for histomoniasis
(blackhead) and other protozoal infections in poultry and game
birds.

In the EU, DMZ has the anomalous legal status of being in Annex
IV (therapeutic use prohibited) of Regulation 2377/90 but
permitted for the prevention of histomoniasis when used as a
feed additive under Directive 70/524/EEC.
For the latter purpose it is available as a premix.
USE IN FISH
(a) Food-producing fish
The use of DMZ for the treatment of 'white spot' (Ichthyophthirius
multifiliis) infection or "lck") in rainbow trout was investigated by Rapp
(1995).

The rationale for the work was that in Germany malachite green is
banned for food-producing fish species, and the belief that immersion
in potassium permanganate was the only other possible treatment but
had serious target species safety problems.

(In fingerlings at 16-17°C it was said to have "had a catastrophic

effect"). Combinations of potassium permanganate immersion with in-
feed DMZ at various different temperatures were tested.
(b) Ornamental fish
Nitroimidazoles have been recommended for bath treatment of
some ornamental species, especially for 'hole-in-the-head'
disease, a necrotic fistulous condition thought to be initiated by
the protozoan, Hexamita (syn. Octomita).

Dipping in 7 ppm metronidazole or 5 ppm DMZ is usual.

Where malachite green is not available nitroimidazoles may also

be used for 'velvet disease' caused by the protozoan, Oodinium,
but twice the concentration used for 'hole-in-the-head' disease is
recommended.

Where a concentrated solution of DMZ is not commercially

available it is possible to prepare a metronidazole dip solution by
grinding tablets intended for human medicine with a pestle and
mortar.
Formalin: For control of external protozoa
Dose: Salamonids above 50OF upto to 170ul/L for us 1 hour below
50OF UP+250ul/L upto 1 hour.

All others finfish upto 250ul/L upto 1 hour.

Shrimps in tanks and race ways 50-100ul/L upto 4 hours daily.

NaCl: For treating external protozoa 3% for 10-30 min by

immerssion

Calcium Oxide (CaO): External protozoa of fingerling and adults

2000 mg/l for 5 seconds

KMnO4: It has safety problems for target species

In fingerlings catastrophic effect is seen in turn dose rate
CuSO4: is used to control of bacterial Gill disease, but it can’t
be recommended due to environmental problem.

Its mode of action is astringent rather than antibacterial, it is

active against protozoa and has a particular effect on
Amyloodinium and Cryptocaryon infection in marine aquaria
than in F.W.
CuSO4 is lethal to marine invertebrates. so it can’t be used in
community aquaria controlling these organism and CUSO 4 is
admissible fully by immersion. Exposure is prolonged, for Ex :
10 days.
The normal procedure is to prepare a stock solution of
400mg/ltr. of CuSO4 penta hydrate and this stock solution at 1
ml/ltr gives a concentration of 0.1 ppm & used at range of
0.16-2ppm
Higher concentration is used for hard water
Leteux – Meyer Mixture
It is a mixture of Formalin & malachite green.

The limited efficiency of either formalin or malachite green

for treatment of WSD at concentration less than toxic for
majority of American sp of culture fish.

Safe concentration of formalin always to be repeated in

target species leading to more material and labour cost.
Similarly to malachite green (MG)

So malachite green (MG) and formalin could be formulated

which were sufficient and safe for target species.
Lateux meyer mixture is now widely used, is formulated as a
concentrate by dissolving 3.3g malachite green in 1 liter
formalin.
It is used 1:40,000 or 2.5ml in 100 liter depicting 25ppm or
1:67,000 or 1.5ml in 100 liter depicting in 15 ppm.

They will contain 0.083 & 0.05PPM of malachite green

respectively - a higher concentration for 1hour treatments
and lower for prolonged treatment.

A single treatment is usually effective for infection with costia

or Ichthyoboda and trichodina, scyphidia and trichochyra