AN OVERVIEW ON ANTHELMINTIC DRUG RESISTANCE AND NATURAL REMEDIES A POSSIBLE SOLUTION

Dr. Yash Bhargava, MVSc  (Teaching Associate  IPVS, DUVASU),
Dr. Pradeep Kumar MVSc, PHd (Assistant Professor Department of veterinary Parasitology, COVSc  & AH, DUVASU, Mathura),
Dr. Shardendu Narayan Giri  MVSc  (Teaching Associate  IPVS, DUVASU),
Dr. Shubham Kumar, MVSc (Teaching Associate IPVS, DUVASU)   
Dr. Sudaksha Saraswat BVSc & AH (Teaching Associate IPVS, DUVASU) 
*Corresponding author-   Dr. Shardendu Narayan Giri  , dr.shardendu007@gmail.com                                          

Anthelmintics are a group of antiparasitic drugs that helps to expel the parasitic worms (helminthes) and other internal parasites from the body by either stunning or killing them, without causing significant damage to the host organism. Anthelmintics are also called as antihelmintics. Anthelmintic compounds share a common mode of action. In the free living nematode Caenorhabditis elegans, AMs act on a group of glutamate-gated Cl−channels which appear to be expressed in defined muscle cells, and possibly neurons, in the pharynx of worms. Glutamate is an inhibitory neurotransmitter in the pharynx and Glu, Ivermectin and milbemycin D act by increasing Cl− currents when added to expressed receptors. It is likely that AMs paralyze worm muscle either by mimicking and/or influencing the binding of Glu to its receptor and by these types of mechanism of action the helminthes are killed, paralyses or inhibit there growth which ultimately leads to reduction in their number by their removal from the body or by partially digestion in the GIT. But now days many of these compounds are ineffective to the helminths due to genetic changes, adaption, selection and biological changes in the body. Anthelmintic resistance in the parasite of the cattle is an emerging problem. Resistance is the ability of worms in a population to survive treatments that are generally effective against the same species and stage of infection. Thus now resistance to anthelmintic drugs is became a big problem which results for the discovery of new drugs. There are some natural methods to cure it by using diatomous earth and certain plants are also used to cure the infestation of helminthes in the body as they are not having any adverse effect on the body of the animal and the helminthes are also unable to develop resistance against it.

Anthelmentic are of two types-

  1. Vermicide: These are the agents which are destructive to worms which means by the killing of the worms as piperazine and hexylresorcinol used for round worms (ascarids), quinacrine for tapeworms. These drugs are toxic thus also given with care.
  2. Vermifuge: These are the agents which help in the expulsion of worms and other parasites from the intestinal tract.

Some of the anthelmentics are used for nematodes are- Diethylecarbamazine, ivermectin, mebendazole, pyrental pamoate and thiabendazole for trematodes- praziquantal for cestodes- albendazole, niclosamide.

Anthalmentic resistance: It is defined as the lack of the drug efficacy in a population of helminth parasites that was previously sensitive to the drug at a defined dose and in a defined host.Resistance is present when there is a greater frequency of individuals within a population able to tolerate doses of compound than in a normal population and is heritable.As resistance develops further, more worms survive treatment until treatment failure occurs for these species or stages too. Once resistance is present, the population does not appear to revert to susceptibility, so the aims of resistance control are to prevent the first steps in the development of resistance and then to delay the accumulation of resistance genes.

The alternative alleles are already present in the genome of the parasite for the resistance of the drugs due to very high genetic diversity of the parasites, thus because the response of the drug is not uniform to the parasite population and there is also the spontaneous multiple origin of resistance by spontaneous and recurrent mutations. Some of the mutant allele parasite also grow/ develop factor in the population by their life cycle and decrease in the in the generation time increase in the fecundity by it there is spread of the resistance in the population will increase.  

Selection for resistance can be done by estimate the numbers of free living stages and stages within the host, includes the effects of immunity and the efficacy of treatment, and considers the genetics of resistance. Under dosing, like using an ineffective drug, is likely to enhance selection for resistance. The efficacy above 99.99% will tend not to select for resistance because there are too few survivors to effectively reproduce.

Refugia refers to the population of worms not exposed to treatment (and hence, selection) with the compounds used. The higher the proportion of worms in refugia, the more slowly resistance develops and remain susceptible, and will dilute resistant worms in the population.

Now a day’s Haemonchus is 100% resistance to Ivermactin and 92% resistance to Fenbendazol.

Anthelmintic resistance develops due to-

  1. Increase frequency of treatment
  2. Underdosing
  3. Improper administration of drug
  4. Introducing of animal resistant worms
  5. Dosing in winter or before turn out leads to rapid development of anthelmintic resistance in haemonchus.

Test for diagnose anthelmintic resistance

  1. Drench response
  2. Fecal egg count reduction test (FECRT)
  3. Larval development assay (lab based) (FDA)
  4. FAMACHA
  5. SCOOP
  6. Larval paralysis
  7. Egg hatch assay (EHA)
  8. Tubulin binding
  9. Adult development
  10. Larval migration inhibition assay (LMIA)
  11. Micromotility meter test (MMT)
  12. Larval feeding assay (LFA)
  13. WAAVP (molecular detection technique)

Each test is used for diagnosis of resistance to a specific anthelmintic which works on the specific stage of the life cycle of the parasite.

Alternative Natural Dewormers

Bearing in mind that the list of reports on the use of the so called “alternative natural” dewormers is overwhelming, suggestions are proposed in order to evaluate the informative value and more importantly, use of the natural materials to enhance survival of parasitized sheep and goats, including the use of diatomaceous earth as an alternative anthelmintic. DE is used to control many invertebrate pests, including grain storage invertebrate pests and as an alternative anthelmintic product fed to domestic animals (poultry, sheep and cattle) for gastrointestinal parasite control, although the small number of efficacy studies show mixed results. But DE did not express an anthelmintic effect as expressed by eggs per gram of feces when naturally infected goats (Haemonchus contortus, Eimeria and Thichostrongylus spp.) were fed DE at 50, 100 and 150 μg/kg body weight.

Alternative natural dewormer as an organism

Nematode-trapping fungi have documented the potential as a biological control agent against the free-living stages under experimental and natural conditions. These fungi occur in the soil throughout the world where they feed on a variety of free-living soil nematodes. These fungi capture nematodes by producing sticky, sophisticated traps on their growing hyphae. Of the various fungi tested, Duddingtonia flagrans, has the greatest potential for survival in the gastrointestinal tract of ruminants. After passing through the gastrointestinal tract, spores germinate and looped hyphae trap the developing larval stages in the fecal environment. This technology has been applied successfully under field conditions in all livestock species, and is an environmentally safe biological approach for control of worms under sustainable, forage-based feeding systems.

The fungi Nematophagus reduces the infectivity level on pastures and acts as prophylactic fungi. Thick walled resisting spores is produced by Duddingtonia flagrans, chlamydospores are having the ability to successfully pass through the GIT and can survive in fecal material and rapidly germinate on stimulation then spread on the fresh dung and capture the infective larvae of most GIT ostertagia, haemonchus, nematodirus, as before their migration towards the pasture.

Minerals

Copper oxide wire particle (COWP) how to use – 5gm of capsule of COWP have 96% effect on H contortous and 56% effect on ostertagia. Phosphorus has been supplemented to prevent worm establishment and adequate copper levels are necessary for development of immunity to GIT and the addition of molybdenum @6-10 mg/day decreases the worm load in lambs molybdenum increases jejunal mast cells and blood eosinophil number.          

Anthelmentic plants

There are many plants which are having anthelmintic property because of having some active components in them which are responsible for having anthelmintic property against tapeworms, roundworms, flatworms and others also are tabulated as-

S.noName of plantCommon nameActive componentPart of plantHeleminth affected
1Ferula asafetidaHingFerulicacid & UmbelliferoneResinBroad spectrum
2Embelia ribesFalse black pepper & DevnagariEmbelin (tannin & glycosides)SeedTapeworm
3Picrasma excelsBitter woodQuassinoids       –               –
4Chenopodium ambrosioidesWorm seed        –       –Haemonchus contortus
5Echinacea purpureaPurple coneflower and scurvy root.glycol-proteins, aklomide, and flavonoids.           –                         –
6Trifolium repensDutch clover /white clover         –Areal shootHymenolepis diminuta
7Ficus insipida          –FicinLatexSyphacia obvelata, vampirolepis nana.
8Cucurbita maximaWinter squash plant         –SeedTape worm (trematode cestode &nematode)
9Tachyspermum ammiAjwain plant         –SeedHaemonchus contortus
10Thymus vulgaris Thymol & camphorLeaves & stemHook worms
11Punica granatum PomegranatePelletierine, AlkaloidRoot, stem,barkNematodiasis &filariform larvae of haemonchus contortus
12Mimusops elengiSpansh cherry ,bullet woodTaraxerol, ursolic acidStem barkAscardia galli
13Juglan nigra &tansyBlack walnut               –       –Enterobius vermacularis (pin worms)
14Moghinia vestita          –Genistien & various extractsTuberous root & peel.Trematodes and nematodes
15Nigella sativaKala jiraThymoquinone &alpha-Pinene       –Tapeworm &hook worms
16Carica papayapapayaBenzyle- isothiocynateSeedAscaris lumbricoides & Ascaridia galli
17Astemisia annuaSweet worm woodArtemether       –S heamatobium, S japonicum, S mansoni
18Melia azedarachChinaberry tree, Pride of India, bead-treeTannin, phenolic compounds and steroidFruit and leavesTapeworm
19Ocimum sanctumSacred basilEugenol(1-hydroxy-2-methoxy-4-allylbenzene), beta-cryophylleneLeaves 
20Commiphora sppGum myrrh / MyrrhMyrrhAromatic resinFasioliasis , Schistosomiasis