1. Nematoda VMP 920 Infection & Immunity II Veterinary Parasitology

2. Nematode Phylogenetic Tree pict

3. Nematodes Cylindrical Dioecious Complete gut Cuticle Pseudocoelom Longitudinal muscles only

4. Pasture-borne Nematodes Worm Ecology on Pasture Host Immunity Dewormer Resistance

5. Pasture-borne Nematodes Worm Ecology on Pasture

6. Worm Ecology On-Pasture Basic Life Cycle 1. Adult worms in the definitive host lay eggs 2. Eggs passed in the feces 3. L1 & L2 on-pasture feed on microbes

7. Worm Ecology On-Pasture Basic Life Cycle (continued) 4. L3 (infective stage) a. retains L2 molt sheath (gives some protection from desiccation) b. non-feeding thus limited energy stores. c. ingested by host (deadly dew drop)

8. (Deadly Dew Drop)

9. Worm Ecology On-Pasture 4. L3 (infective stage) d. longevity depends on environmental conditions i. Moderate temps (mild) + high humidity (wet) = ↑ longevity (few months) ii. Extreme heat (hot) + low humidity (dry) = ↓↓ longevity (desiccation of L3 (& L1 & L2)) iii. extreme cold = ↓ longevity (very few larvae on pasture survive the winter) iv. ↑ heat = ↑ activity = ↑ use of energy stores = ↓ longevity

10. Pasture-borne Nematodes Host Immunity

11. Host Immunity v/s Worms 1. Young animals are naïve & fully subject to dose-dependent pathology 2. As animals age, acquired immunity develops decreasing likelihood of over-whelming dose pathology. 3. Host immunity usually: a. eliminates incoming larvae b. sequesters larval worms in somatic tissues

13. Host Immunity v/s Worms 4. Host immunity against a specific worm species is usually not permanent. (New infections are not prevented.) 5. Host immunity against a specific worm species is usually “active” only in the presence of adult worms. = Premunition

15. Host Immunity v/s Worms 6. The elimination of adult worms (& the Premunition effect) may result in serious post- treatment pathology, due to reactivation of an over-whelming population of arrested (hypobiotic) larvae.

19. Host Immunity v/s Worms 7. Stress (ex. Pregnancy) can reduce the efficacy of the host immune response, allowing an increase in the number of adult worms and eggs in the feces (i.e. Fecal Worm Egg Count (FWEC)) = Periparturient rise or Spring rise. (Why would a periparturient rise be advantageous to the worm population?)

21. Pasture-borne Nematodes Dewormer Resistance

22. Popular dewormers & their mechanisms Ivermectin – hyperpolarization of neurons – death by paralysis Resistant worms circumvent neural hyperpolarization Fenbendazole – blocks mitochondrial function -- death by lack of energy Resistant worms circumvent mitochondrial block Pyrantel – Disrupts function of neuromuscular junction -- death by tonic paralysis Resistant worms circumvent neuromuscular disruption A genetic sub-population of worms develop the ability to circumvent a specific dewormer’s mechanism of action.

23. Dewormer Resistance Characteristics of Resistance 1. A genetic sub-population of worms develop the ability to circumvent a specific dewormer’s mechanism of action. 2. Resistance is a genetic-linked phenotype => passed to offspring.

24. Development of Resistance 1. Repeat & frequent exposure to a specific dewormer promotes the development of resistance to that specific dewormer. 2. Under-dosing of a specific dewormer accelerates the development of resistance. 3. Frequent deworming eliminates the sub- population of susceptible worms; leaving a population of predominantly resistant worms.

26. Selective Deworming & Refugia 1. Allowing non-clinical animals to remain infected allows the sub-population of susceptible worms to remain dominant => extends the longevity of a particular dewormer’s efficacy on a particular farm. 2. Refugia = the sub-population of susceptible worms.

28. Important Points 1. Basic life cycle of Pasture-borne parasites, Deadly dew drop, characteristics of L3, effects of temp & humidity on L3 longevity. 2. Generalized Host immune response to worms. (naïve host, immuno-competent host, premunition, periparturient rise) 3. Dewormer resistance. (general concept of a resistant worm in relation to a particular dewormer, consequence of genetic-linked phenotype, how untargeted v/s selective deworming effects the worm population, concept of refugia.)