TREATMENT AND CONTROL METHODS IN    PARASITOLOGY1   Part 1: Antiparasitic
INTRODUCTION There is a wide variety of parasites and an equally wide  range of substances and practices used in their tr...
IMPORTANCE OF UNDERSTANDING PARASITE LIFE CYCLESFOR EFFECTIVE TREATMENT AND CONTROL   To understand parasite life cycles ...
   For example in UK, rainfall and temperature are the key factors    determining the transmission efficiency of Fasciola...
HOW A PARASITE’S LIFE CYCLE CAN INFLUENCEITS TREATMENT AND CONTROL? Direct life cycle Life cycle involves one or more sp...
DIRECT LIFE CYCLE   Importance in treatment/ control    - Provision of sanitation and basic hygiene practices can    prev...
LIFE CYCLE INVOLVES ONE OR MORE SPECIES OFVECTOR   Importance in treatment/ control    - Disease transmission can be cont...
LIFE CYCLE INVOLVES ONE OR MOREINTERMEDIATE HOSTS   Importance in treatment/ control    - Disease transmission can be con...
PARASITE HAS A VARIETY OF DEFINITIVE HOSTS   Importance in treatment/ control    - Reservoir hosts are a potential source...
PARASITE HAS LIFE CYCLE STAGES THAT AREEXPOSED TO THE ENVIRONMENT   Importance in treatment/ control    - Environmental c...
SEQUENCE AND TIMING OF LIFE CYCLE STAGESWITHIN A HOST   Importance in treatment/ control    - Optimal time for diagnosis...
LOCATION WITHIN HOST   Importance in treatment/ control    - Optimal time for diagnosis   Application of life cycle know...
PART 1: TREATMENT   Antiparasitic- Chemical/ Pharmaceutical drugs                                   13
PROPERTIES OF AN IDEAL ANTIPARASITICDRUG OR TREATMENT REGIME Kills 100% of the parasites Broad spectrum Rapid action P...
KILLS 100% OF THE PARASITES Obviously drugs need to be effective Need to kill all the parasites found in (or on) the bod...
BROAD SPECTRUM   Drugs that have a broad spectrum of action are beneficial    since they can be used to treat a variety o...
RAPID ACTION   Drugs that kill parasites rapidly reduce the chances of    resistance developing   Since less time the pa...
PROVIDES LONG-LASTING PROTECTION   Can reduce the cost of treatment   Can protect the hosts from the same disease    inf...
SIMPLE TO ADMINISTER Drugs are seldom administered as compounds on their  own. Most of the drugs are ‘formulated’ with a...
   Ease of administration is important in order to ensure    compliance and can be treated quickly with minimum of    fus...
REQUIRES ONLY ONE OR TWO TREATMENTS TO ACHIEVEA CURE   The fewer the number of treatments required to remove the    paras...
SAFE (DOES NOT CAUSE HARMFUL SIDE-EFFECTS) There is always a risk that the drugs will harm the hosts. The chance is redu...
DOES NOT HAVE CONTRA-INDICATIONS   All chemicals are toxic if taken in sufficient concentration.   It is very rare for t...
   For example: Ivermectin – is considered safe for use in    most mammals.   In certain breeds of domestic dogs, very l...
AFFORDABLE TO THE INDIVIDUAL/POPULATION   Cost, a major consideration for any treatment regime –    especially for poor p...
   Example : albendazole and praziquantel    - In the early 2000s, tablets of albendazole  US$0.20    per tablet and pra...
CHEMICALLY STABLE WITH A LONG SHELF LIFE   The cost of drug is partly linked to its chemical stability.   If the drug is...
DOES NOT CAUSE HARM TO THE ENVIRONMENT   The environmental impact of the drug should be    considered.   All the drugs t...
   Residues of drugs can persist in the environment under    suitable conditions.   Therefore affect susceptible inverte...
Anticipated exposure routes of veterinary drugs in the environment   30
ANTIPARASITIC   Antiparasitics are a class of medications which are indicated    for the treatment of parasitic diseases ...
ANTIPROTOZOAL Kinetoplastid protozoa Anaerobic protozoa Sporozoan protozoa                           32
KINETOPLASTID PROTOZOA   Human sleeping sickness are usually treated with    suramin, though occasionally pentamidine is ...
   Suramin is also used to treat trypanosome in infections in    equines and camels.   Quinapyramine works well in camel...
ANAEROBIC PROTOZOA   Trichomoniasis, giardiasis and amoebiasis in both humans and    domestic animals can all be controll...
SPOROZOAN PROTOZOA   Coccidiosis, especially in broiler chickens, is controlled by    the continuous administration of dr...
   Malaria, which is the most common of the parasitic diseases of    humans, can be treated by a wide range of drugs, all...
ANTINEMATODES   A large number of drugs are available to control the    gastrointestinal nematode infestations of domesti...
   A large number of drugs are also available for the    treatment of human gastrointestinal infestations, including    p...
   Tissue-dwelling nematodes, the filariae     diethylcarbamazine   Adult worms can be eliminated with suramin   Dieth...
ANTITREMATODES Sheep and cattle infected with liver fluke are likely to contain all three developmental stages:1) early ...
   Most drugs are active against the adults, including    rafoxanide, closantel, nitroxynil, nidoiolan, bromophos, bit   ...
   The treatment of schistosomiasis in humans relies on three    drugs, oxamniquine, metrifonate and praziquantel.   Oxa...
ANTICESTODES   A number of chemotherapies are available to control these    infections in both farm and companion animals...
   Niclosamide works only against adult worms in the gut;   Albendazole and praziquantel can kill Taenia solium    cysti...
AntinematodesAnticestodes     AnthelminticsAntitrematodes                                 46
 2 types- Broad spectrum- Narrow spectrum                    47
BROAD SPECTRUMClass                  Anthelmintic    Mode of actionBenzimidazoles (BZs)   Thiabendazole   Bind to a specif...
Class                   Anthelmintic   Mode of actionImidazothiaoles –       Levamisole     Mimic the activity oftetrahydr...
Class                       Anthelmintic   Mode of actionMacrocyclic lactones (ML)   Ivermectin     Interfere with GABA-  ...
Class                             Anthelmintic   Mode of action Amino-acetonitrile derivatives   Monepantel     It paralyz...
Narrow spectrum anthelminticsAnthelmintics                Parasite coveredTriclabendazole              Fluke (including im...
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5 disease treatment and control methods 1

  1. 1. TREATMENT AND CONTROL METHODS IN PARASITOLOGY1 Part 1: Antiparasitic
  2. 2. INTRODUCTION There is a wide variety of parasites and an equally wide range of substances and practices used in their treatment and control. Focus on general concepts and also introduce some of the most recent advances in parasitology for treating and preventing parasitic infections. Part 1: Treatment Part 2: Control Part 3: Recent advances 2
  3. 3. IMPORTANCE OF UNDERSTANDING PARASITE LIFE CYCLESFOR EFFECTIVE TREATMENT AND CONTROL To understand parasite life cycles  it is complicated Without knowledge of a parasite’s life cycle, one cannot begin to understand how it is transmitted and how it cause disease. 3
  4. 4.  For example in UK, rainfall and temperature are the key factors determining the transmission efficiency of Fasciola hepatica – principally through their effect upon the snail intermediate host. This factor has enabled the development of a liver fluke forecasting scheme. Which is operated by National Animal Disease Information Service (NADIS). So farmers can use this to determine when their flock is most at risk of infection and therefore should be treated with anthelmintics or if possible moved to less risky pasture. 4
  5. 5. HOW A PARASITE’S LIFE CYCLE CAN INFLUENCEITS TREATMENT AND CONTROL? Direct life cycle Life cycle involves one or more species of vector Life cycle involves one or more intermediate hosts Parasite has a variety of definitive hosts Parasite has life cycle stages that are exposed to the environment Sequence and timing of life cycle stages within a host Location within host 5
  6. 6. DIRECT LIFE CYCLE Importance in treatment/ control - Provision of sanitation and basic hygiene practices can prevent many gastrointestinal parasitic diseases Application of life cycle knowledge - Washing fruit and vegetables in clean water can remove protozoan cysts and helminth eggs 6
  7. 7. LIFE CYCLE INVOLVES ONE OR MORE SPECIES OFVECTOR Importance in treatment/ control - Disease transmission can be controlled by targeting the vectors Application of life cycle knowledge - Bed-nets can prevent mosquitoes transmitting malaria 7
  8. 8. LIFE CYCLE INVOLVES ONE OR MOREINTERMEDIATE HOSTS Importance in treatment/ control - Disease transmission can be controlled by targeting the intermediate hosts Application of life cycle knowledge - Drainage to remove the habitat of snail intermediate hosts of Fasciola hepatica 8
  9. 9. PARASITE HAS A VARIETY OF DEFINITIVE HOSTS Importance in treatment/ control - Reservoir hosts are a potential source of infection Application of life cycle knowledge - Schistosoma japonicum has numerous reservoir hosts which can contaminate paddy field etc with eggs 9
  10. 10. PARASITE HAS LIFE CYCLE STAGES THAT AREEXPOSED TO THE ENVIRONMENT Importance in treatment/ control - Environmental conditions can promote or limit infection Application of life cycle knowledge - Composting can kill the infective stages of many gastrointestinal parasites 10
  11. 11. SEQUENCE AND TIMING OF LIFE CYCLE STAGESWITHIN A HOST Importance in treatment/ control - Optimal time for diagnosis Application of life cycle knowledge - Mf of Wuchereria bancrofti exhibits periodicity 11
  12. 12. LOCATION WITHIN HOST Importance in treatment/ control - Optimal time for diagnosis Application of life cycle knowledge - Cattle should be treated for warble fly infections before the larvae reach their resting site 12
  13. 13. PART 1: TREATMENT Antiparasitic- Chemical/ Pharmaceutical drugs 13
  14. 14. PROPERTIES OF AN IDEAL ANTIPARASITICDRUG OR TREATMENT REGIME Kills 100% of the parasites Broad spectrum Rapid action Provides long-lasting protection Simple to administer Requires only one or two treatments to achieve a cure Safe (does not cause harmful side-effects) Does not have contra-indications Affordable to the individual/population Chemically stable with a long shelf life Does not cause harm to the environment 14
  15. 15. KILLS 100% OF THE PARASITES Obviously drugs need to be effective Need to kill all the parasites found in (or on) the body of the host Should be less harmful to the host cells than to the parasites. This selective toxicity is hard to achieve for antiparasitic drugs. For example praziquantel if only effective against adult schistosomes but not good killing the developing schistosomulae. If the drug is not effective killing 100% parasites, it will 15 increases the risk of resistance developing.
  16. 16. BROAD SPECTRUM Drugs that have a broad spectrum of action are beneficial since they can be used to treat a variety of parasites. For example the avermectin drugs such as ivermectin and doramectin  active against gastrointestinal nematodes as well as ectoparasites such as lice, fleas and ticks 16
  17. 17. RAPID ACTION Drugs that kill parasites rapidly reduce the chances of resistance developing Since less time the parasite has to interact with the drug, the less chance there is of it evolving a physiological means of counteracting it. 17
  18. 18. PROVIDES LONG-LASTING PROTECTION Can reduce the cost of treatment Can protect the hosts from the same disease infection. 18
  19. 19. SIMPLE TO ADMINISTER Drugs are seldom administered as compounds on their own. Most of the drugs are ‘formulated’ with a cocktail of chemicals The composition of which varies with the intended means of delivery e.g liquid, tablet or injection Alters the effectiveness of the drug The formulation can influence drug’s stability, toxicity to both host and target parasite, rate of absorption and excretion, bioavailability and pharmacokinetics. 19
  20. 20.  Ease of administration is important in order to ensure compliance and can be treated quickly with minimum of fuss. Drugs can be taken without supervision tablets and liquid Injection – intravenous or intra- peritoneal  supervised by trained medical personnel For domestic animals  Dosing gun, ‘pour on/ spot on’ formulation on the body of animal, slow-release bolus 20 (placed the drugs into rumen using special device.
  21. 21. REQUIRES ONLY ONE OR TWO TREATMENTS TO ACHIEVEA CURE The fewer the number of treatments required to remove the parasite, the better the chance of patient compliance Especially if the treatment has to be delivered at a medical centre or veterinary surgery If repetitive treatments are required, then there is a high possibility that when the patient starts to feel better or animal seems to be improving, the patient of owner will cease or forget to complete the treatment regime. This will increase the possibility that the parasite will persist and increases the chances of any resistance developing. 21
  22. 22. SAFE (DOES NOT CAUSE HARMFUL SIDE-EFFECTS) There is always a risk that the drugs will harm the hosts. The chance is reduced if the drug selectively acts upon a physiological process that does not occur in the host. For example: Cryomazine and Diflubenzuron  targeting the moulting process in arthropods - Safe to use in mammal because no comparable metabolic pathway.- Cryomazine  interferes with the deposition of chitin in the cuticle- Diflubenzuron  inhibits chitin synthesis 22
  23. 23. DOES NOT HAVE CONTRA-INDICATIONS All chemicals are toxic if taken in sufficient concentration. It is very rare for the drug to be so specific that only interacts with a single physiological process. Patients normally will cease treatment if the drug induces unpleasant side effects such as nausea and vomiting. The host’s health and generic constitution can influence the way it respond to drugs. 23
  24. 24.  For example: Ivermectin – is considered safe for use in most mammals. In certain breeds of domestic dogs, very low concentration induce neurological symptoms –e.g hypersalivation, ataxia, blindness, respiratory distress, which can be fatal. 24
  25. 25. AFFORDABLE TO THE INDIVIDUAL/POPULATION Cost, a major consideration for any treatment regime – especially for poor people living in developing countries. Even if the drug is ideal in every way, if it is too expensive then it becomes irrelevant to all but those who are rich. Drugs that are still in patent are usually expensive  the manufacturer needs to make sufficient profit to recoup the costs of development and fund the development of new drugs. Once drug is out of patent it can be manufactured by any commercial concern and its cost usually declines. 25
  26. 26.  Example : albendazole and praziquantel - In the early 2000s, tablets of albendazole  US$0.20 per tablet and praziquantel  US$3.00 per tablet. - When out of patent, tablets of albendazole  US$0.02 per tablets and praziquantel  US$0.07 per tablets. 26
  27. 27. CHEMICALLY STABLE WITH A LONG SHELF LIFE The cost of drug is partly linked to its chemical stability. If the drug is stable and has a long shelf life, and does not need to be stored in a fridge is usually going to be cheaper. It can be bought in bulk and can be stored and transported at low cost. It also will instantly available when needed. 27
  28. 28. DOES NOT CAUSE HARM TO THE ENVIRONMENT The environmental impact of the drug should be considered. All the drugs that go into us and our animals are ultimately passed out of us in one way or another and they enter the environment. Sometimes drug are metabolized completely But very often breakdown products or unmetabolized drug are passed in urine or faeces or in the milk or present in the meat. 28
  29. 29.  Residues of drugs can persist in the environment under suitable conditions. Therefore affect susceptible invertebrates both in soil and in surrounding water systems. 29
  30. 30. Anticipated exposure routes of veterinary drugs in the environment 30
  31. 31. ANTIPARASITIC Antiparasitics are a class of medications which are indicated for the treatment of parasitic diseases such as nematodes, cestodes, trematodes, infectious protozoa and amoebas. There are different medications suited to different types of parasites. - Antinematodes  are one group that can address infection with nematodes - Anticestodes  these target tapeworms - Antiprotozoal  treat parasitic infections caused by protozoa that enter the body - Antitrematodes  treat parasitic infections caused by trematodes 31
  32. 32. ANTIPROTOZOAL Kinetoplastid protozoa Anaerobic protozoa Sporozoan protozoa 32
  33. 33. KINETOPLASTID PROTOZOA Human sleeping sickness are usually treated with suramin, though occasionally pentamidine is used. Where trypanosomes are present in the CNS, are treated with melarsaprol or eflornithine (Trypanasoma brucei gambiense infections only) Pentamidine  intramuscular injection Eflornithine is active by the oral route. 33
  34. 34.  Suramin is also used to treat trypanosome in infections in equines and camels. Quinapyramine works well in camels, pigs and cattle, but Homidium bromide, isometamidium and diminazine aceturate are the principal drugs used to control such diseases in sheep and cattle Chagas disease  orally administered courses of nifurtimox or benznidazole are effective. For leishmaniasis remains the antimonials  sodium stibogluconate and meglumine antimonate  administered by 34 injection
  35. 35. ANAEROBIC PROTOZOA Trichomoniasis, giardiasis and amoebiasis in both humans and domestic animals can all be controlled by metronidazole. This drug is orally active, very efficacious and relatively free of side effects. The alternative in giardiasis is mepacrine The alternatives in amoebiasis are diloxanide, which is only effective in non-invasive cases, and tinidazole, which is another potentially mutagenic 5-nitroimidazole. Subsequently, satranidazole, yet another 5-nitroimidazole, was marketed in some territories for giardiasis and amoebiasis. 35
  36. 36. SPOROZOAN PROTOZOA Coccidiosis, especially in broiler chickens, is controlled by the continuous administration of drugs in the diet. Currently, the ionophores such as lasalocid, salinomycin and especially monensin are the coccidiostats of choice. Others, such as amprolium, clopidol, decoquinate and robenidine, are however still used. 36
  37. 37.  Malaria, which is the most common of the parasitic diseases of humans, can be treated by a wide range of drugs, all active by the oral route. Until recently, the standard drugs were chloroquine for treatment, ptimaquine to prevent relapse (Plasmodium vivax malaria) and chloroquine or pyrimethamine + sulphadoxine (Fansidar) or pyrimethamine + dapsone (Maloprim) for prophylaxis. Babesiosis in cattle can be controlled by diminazine aceturate, and theileriosis by parvaquone (East Coast Fever only), buparvaquone and possibly halofuginone. 37 Injectable formulations are available in all cases
  38. 38. ANTINEMATODES A large number of drugs are available to control the gastrointestinal nematode infestations of domestic animals. Piperazine (small animals), haloxon (horses), dichlorvos (especially pigs), napbthalophos (sheep), the benzimidazoles, the benzimidazole carbamates and their prodrugs (e.g. thiabendazole, albendazole, oxfendazole, fenbendazole), morantel (cattle), pyrantel (horses and dogs), levamisole and ivermectin. 38
  39. 39.  A large number of drugs are also available for the treatment of human gastrointestinal infestations, including piperizine, thiabendazole, albendazole, mebendazole, lev amisole, pyrantel and bephenium. All are active via the oral route. The most commonly used is mebendazole, which probably covers the broadest spectrum. 39
  40. 40.  Tissue-dwelling nematodes, the filariae  diethylcarbamazine Adult worms can be eliminated with suramin Diethylcarhamazine was used also for onchocerciasis Ivermectin also might be macrofilaricidal. 40
  41. 41. ANTITREMATODES Sheep and cattle infected with liver fluke are likely to contain all three developmental stages:1) early immature stages2) immature stages3) adults. Treatment of animals harbouring such mixed-stage infections will be ineffective unless all three stages are eliminated. Unfortunately most drug to treat trematodes infection is a stage specific. 41
  42. 42.  Most drugs are active against the adults, including rafoxanide, closantel, nitroxynil, nidoiolan, bromophos, bit hinol sulphoxide, oxydozanide and albendazole. Diamphenethide is very effective against early immature and immature stages, but is not against adults. Triclabendazole, however, works well against all stages. Fluke infections in humans are controlled by praziquantel 42
  43. 43.  The treatment of schistosomiasis in humans relies on three drugs, oxamniquine, metrifonate and praziquantel. Oxamniquine works well against Schistosoma mansoni Metrifonate against S. haematobium Praziquantel against both species and also against S. japonicum. All are active by the oral route and are generally well- tolerated 43
  44. 44. ANTICESTODES A number of chemotherapies are available to control these infections in both farm and companion animals, including dichlorophen (mainly companion animals), niclosamide, resorantel, bunamidine, mebendazole (sheep and cattle only), nitroscanate (companion animals only), pyrantel (horses only, at double dosage) and praziquantel (companion animals only). Key drugs for human use are niclosamide, albendazole and praziquantel. All three drugs can be administered via the oral route, work well against adult stages in the intestine and are generally well tolerated. 44
  45. 45.  Niclosamide works only against adult worms in the gut; Albendazole and praziquantel can kill Taenia solium cysticerci Mebendazole and especially albendazole are now being used with some success in cases of hydatid disease due to Echinococcus species 45
  46. 46. AntinematodesAnticestodes AnthelminticsAntitrematodes 46
  47. 47.  2 types- Broad spectrum- Narrow spectrum 47
  48. 48. BROAD SPECTRUMClass Anthelmintic Mode of actionBenzimidazoles (BZs) Thiabendazole Bind to a specific Fenbendazole building block called beta Albendazole tubulin and prevent its Oxfendazole incorporation into certain cellular structures called microbutbules, which are essential for energy metabolism 48
  49. 49. Class Anthelmintic Mode of actionImidazothiaoles – Levamisole Mimic the activity oftetrahydropyrimidines Morantel acetylcholine, a naturally Pyrantel occuring neurotransmitter that initiates muscular contraction 49
  50. 50. Class Anthelmintic Mode of actionMacrocyclic lactones (ML) Ivermectin Interfere with GABA- Eprinomectin mediated Doramectin neurotransmission, causing paralysis and death of the parasite. 50
  51. 51. Class Anthelmintic Mode of action Amino-acetonitrile derivatives Monepantel It paralyzes worms by(ADDs) attacking a previously undiscovered receptor HCO-MPTL-1, present only in nematodes 51
  52. 52. Narrow spectrum anthelminticsAnthelmintics Parasite coveredTriclabendazole Fluke (including immature fluke from 2 days of age)Closantel Fluke (including immature fluke over 5 weeks of age), Haemonchus contortus, Nasal botsNitroxynil Fluke (including immature fluke), Haemonchus contortusPraziquantel Fluke and tapewormDiethylcarbamazine Filariasis worms 52
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