---start--- parasit 11/11/97 internal parasites of ruminants (lec 45 and 46) mainly cattle, 15-20 min of sheep cattle industry in US has two main parts - dairy and beef. totally there are about 120 million cattle in us and about 100 million are beef animals, the rest are dairy. PA is important - agriculture is our largest industry and we have about 34,000 cattle farms. there are a lot of dairy operations here, too. so in the dairy industry there are extensive and intensive methods. extensive involves a lot of grazing. in intensive conditions, animals are mainly penned either inside or outside. intensive operations may have 500-1000 cows, and this is preferred in TX, CA, FL where there is not a lot of good grazing pasture. extensive methods rely on grass pasture as primary source of food/forage for dairy cows. calves raised in pens , grouped by age until 6-8 mos, when they are usually turned out to pasture assuming it is the right season. they are brought in for the fall and winter. at 15-18 mos old they're bred, and they calve at about 2 yrs, then join the milking herd. dairy calves get colostrum from moms, then are removed. beef calves nurse until weaning. most are then culled by the time they are 6 yrs old. beef production consists of feedlots, where calves are raised. cow/calf herds found in southeast, feedlots in midwest. there are fall cycles and spring cycles. calves are weaned at about 6 mos = 4-6 mos old, and go to feedlots immediately after weaning. but some are kept in herds of origin, as stocker cattle. they are kept in herd of origin for several months, grazed on pasture, then they go onto feedlot for finishing at about 1000-1200 lbs. so we're going to discuss clinical, subclinical, epidemiological, and control mechanisms of parasites, with an economical view. farmers raise cattle for money. anything impinging on production is a big problem, be it a clinical or subclinical infection. many of these parasites impinge on production subclinically as well as clinically. so the economic harm is also a problem for the farmer, which we need to address. lost production is lost money. the cow might not be bothered, but the farmer will lose $$. clinical effects of internal parasites of cattle: parasite prevalence rates of infection are about 90% of all cattle - but most do not show clinical signs. those that do may experience: diarrhea, pneumonia, edema, wasting, anemia a healthy cow with no clinical signs is still almost certainly infected with one or more parasites, if it is out on pasture. and production is probably affected. subclinical effects of infections: reduced wt gain, reduced milk production, carcass/organ condemnation, decreased feed efficiency, delayed breeding age. the sooner you breed, the sooner you milk,the more money you make, so... in beef cattle, they usually assess losses on the basis of short term productivity losses - wt gain. they chart wt gain and compare parasitized v nonparasitized, treated v nontreated, etc. 99% of the time, even subclinical infections produce reduced rate of wt gain. in dairy cattle, similar things are seen. a high percent of animals have nematode infxns, but most have low egg counts and low worm burdens and no signs. dairy cattle - if you tx lactating cows with anthemlmintics, milk production will increase or not increase depending what study you read. the drug companies are peddling a lot of drugs to convince farmers to tx adult dairy cows, rid them of low parasite burdens, and increase production. dr j is showing us a chart of lactation curve - the area under the curve is the milk production. this animal treated during lactation has an increased area under the curve. other studies have shown if you treat at parturition, the increase in milk production is much greater. the problem with these studies is, within a herd, there is huge variation in milk production. so you may show an increase in production, but b/c of normal variation, std deviation is so great that no study has ever shown statistically significant increases in milk production. on the other hand, there is good evidence that if we tx clinical and subclinical in young heifers before they enter milking herd, we will increase production. there is also good evidence that clinical and subclinical infections in heifers can cause serious economic losses. you have young dairy heifers on pasture and growing, and turn them on to pasture in early april, and if you measure their wt gain over the grazing season, and compare treated vs untreated cows, the treated group has highly statistically significant wt gain over the untreated cows. about 50 kg increase in the treated group. important nematodes of cattle: ostertagia ostertagi haemonchus placei trichostrongylus spp cooperia spp etc cestode/trematode fasciola heptaica monezia another one protozoa giardia, cryptosporidia, eimeria, sarcocystis, neospora (see lists in handout) start with first: giardia: cysts in tissue on the slide here stained with methylene blue. giardia is more pathogenic than we used to think. may be important component in etiology of diarrhea in calves. giardia is usually dxd by finding trophozoites in fecal smears or more often cysts in Zn sulfate fecal floats, often after diarrhea doesn't respond to other tx. there is no approved tx for giardiasis in calves. best way to deal with it is by prevention, b/c it flourishes under conditions of overcrowding and poor sanitation. just like pigs, with isospora suis, this is a parasite whose significance has increased with the increased confinement of animals. you don't see this in cow/calf pasture beef herds. you see it in indoor cows. crowded and sad cows. to tx giardia in cows: Fendbendazole 5 mg/kg daily for 3 days seems to work. this isn't a labelled use for the drug. probably it will be approved for this use within 12 mos. it's already being used by practicioners. [note: anthelmintics can be used on beef and dairy animals but there are some clear restrictions about when and how to use them. many have meat/milk withdrawal time periods. the new drug eprinomectin has a zero withdrawal time. many other drugs have up to 72 - 96 hr withdrawal time, which is too much for a lactating dairy cow. so they use different drugs for lactating cows] [dr j busted on Tripp for asking that question since it indicates he's been skipping class...] cryptosporidia - oocysts are small 4-6 micrometers. recall this is associated with villous atrophy. cryptosporidia are associated with diarrhea in calves and are not host specific - can infect humans et al. now, sporulated oocysts which are infective are acid fast. this is useful for diagnosis. but if you stain diarrhea that is fresh, they are not sporulated. you have to incubate the feces for a couple of days to allow oocysts to sporulate. thereis no effective drug against this parasite but like most other parasites of food animals it is a parasite of confined, overcrowded animals that we can prevent by using good sanitation. the other coccidian that's very important is the eimeria - e.bovis and e.zurnii. importance is mainly in calves under a year, raised indoors. mainly dairy calves. only these two spp seem to be pathogenic in cattle. may cause diarrhea, depression if mild; bloody diarrhea, dehydration, rapid emaciation, death in severe cases. also, we do see sporadic cases of eimerian coccidiosis in older animals - adult dairy cow at NBC broke with severe diarrhea after parturition. initially they thought she had salmonella due to sudden onset hemorrhagic diarrhea. she got dehydrated and died w/in a couple of days.just before she died, someone decided to do a rectal - and felt the corrugated colon where gametogony occurs. took a fecal and they found it was teeming with oocysts. it was too late for this cow. so, with coccidiosis, it can manifest in older animals at times of stress, and there is no more stressful time than parturition. so include coccidiosis on diff list for adult stressed cow with acute onset bloody diarrhea. gametogony occurs in cecum and colon. the second stage is what causes the lesions. clinical signs can be well advanced before oocysts appear. it is the gametogony which is the pathogenic form. there may be no oocysts during onset of clinical signs. may need several samples over 24-72 hrs to see the oocysts. coccidiosis is seen mainly in indoor, crowded cows in pens where feces accumulates. under these conditions, oocysts have time to sporulate, so there is constant reinfection and buildup to pathogenic levels. key to control is good sanitation - avoid fecal contamination of food and water. you need clean, dry environment, no over crowding. prophylactic medication is useful in stress situations. drugs for coccidiosis: amprolium, sulfa drugs, lasalocid, monensin, decoquinate. can give in feed. once an animal has clinical signs, you must isolate it, treat it more aggressively, and give supportive therapy. one problem with excessive reliance on tx rather than control is that clinical signs occur late in life cycle after GI tract is already damaged. diagnostic stage is oocyst in feces. consider the animal is now no longer a calf. it is a growing heifer and then a lactating cow. consider the heifer stage. with respect to control of parasitic gastroenteritis in cattle, we can look at them as two groups: mature milking cows and growing dairy heifers destined to join the herd after first calving. the avg age of first calf is 29 mos. avg age of milking cow is 51 mos. this shows that a constant replacement supply of heifers is vital. growing heifers is a big componenet of dairy industry. parasitic infections result from mixed infections with several gi nematodes. consider the dairy heifer on pasture. the nematodes on pasture become important. we see GI nematodes - ostertagia ostertagi is the main species. lately, we've seen more and more clinical coccidiosis in growing heifers on pasture as well (esp where there is stagnant water which can get contaminated) return to nematode life cycle - preparasitic phase is very dependent on temperature and moisture - moisture is essential for development, and temperature determines the rate of development. in parasitic phase, hypobiosis is the main important factor. so in this area, where there are pronounced seasonal climate changes, the population of GI nematodes varies season to season. whether we measure them as L3 on pasture, or as larvae and adults in hosts, it varies. in north america, hypobiosis controls transmission patterns b/c it occurs regularly from year to year. think of ostertagia - development may occur w/in normal 3 week ppp, or may be delayed at early L4 stage due to arrested development - which will ensure survival during period of unfavorable environmental conditions. it's important b/c it not only influences transmisison patterns, but also when disease outbreaks are seen, and b/c some drugs are not effective against arrested larvae. so take these influences - climate and hypobiosis - and look at how they impact the life cycle of ostertagia ostertagi, we see how it impacts the pattern of transmission depending on regional climactic differences. look at map of US. in N US, inhibition of ostertagia larvae occurs in fall, so they can survive the winters which are long and harsh. in S US, inhibition occurs in spring, allowing the larvae to survive the long hot summer. there is some evidence that the propensity for arrested development is genetic. a northern strain of ostertagia was taken from ohio and transplanted to Louisiana. the louisiana strain was brought to ohio. each strain maintained its original arresting time - eg, it seems to be a genetic imprint defining when they arrest. in Northern US, it may be cold, but some larvae can survive on pasture during winter. they have sheaths, aren't doing much - so they can survive enough to set up infections in animals turned out the next spring. he is showing a chart that I don't understand. assume that animals turned out in spring. low level of passive contamination - will graze, ingest L3, which will grow into adults, eggs will be passed out, eggs will become L3, cows eat more, etc. so contamination of pasture increases. there will be a buildup of nematodes in the host animals as they eat more L3s over the summer as they are grazing. so this is when you see clinical outbreaks of type I ostertagiasis as diarrhea (development of larvae to adults in gastric glands). as fall comes, any L3 eaten will not develop but will molt to L4 and become hypobiotic and wait til spring. pasture no longer being recharged by eggs from infected animals, b/c worm level drops off. L3s on pasture start dropping off (reducing in number). type II ostertagiasis then occurs in late winter/early spring, as a result of the arrested L4s resuming development, leaving gastric glands of abomasum, disrupting the glands, causing severe lesions and diarrhea. we call that type II ostertagiasis. ---break--- patterns of infection in southern US are characterized by hot summer, warm spring, mild winter, green clover, and blue diamonds. the hypobiosis protects parasite from long hot dry summer. stimulus is likely to be rise in temperature, although really we believe it is actually declining level of moisture that occurs in late winter/early spring. just knwo - there is a genetic predisposition to arrest, and probably when they resume development, it is also genetically predetermined, sometimes they stay arrested for 6 wks, sometimes 10 wks - that is predetermined. if you have a late winter, and they all resume development when it is still frozen, they could all die, that's why it is staggered. we're in south now with southern strain. rising temps or declining moisture in early spring signal start of arrest. basically it is the other way around from north. because winter is mild in south, more L3 survive on pasture in winter. that's when we see type I dz. b/c arrested development occurs during summer, and arrested larvae resume in fall, type II occurs in fall/early winter. we'll do pathophysiology of ostertagia tomorrow to get more complex- division b/w fall inhibition and spring inhibition isn't absolute. weather patterns are not absolute between N and S, and vary year to year. it seems there is a transition zone between N and S where there are several strains existing. sometimes in this zone there may be inhibition in spring, fall, or not at all. so in general it is divided into winter-arresting northern and summer-arresting southern strains, but there is this transition zone. so it is logical to assume that some strains occupy this zone and have sl modified patterns. coming back to the north - look at how these patterns develop in growing animals on pasture. in late spring, there is a low level of larvae on the pasture. however, when naive animals are turned out on this pasture, they ingest those L3, which grow to adults in the animals. the small number of adults produced make large numbers of eggs - in naive animals, egg counts are much higher than in older resistant animals. so the pasture is quickly heavily contaminated. eggs become L3 rapidly in warm spring/summer. animals keep grazing, eating L3s, which grow into adults, which make more eggs. it is when you have a heavy adult worm burden that you get Type I ostertagiasis. these adults eventually die off. as fall comes, the new L3s which are eaten no longer become adults. there is a fall off of egg counts and adult worm burden as incoming L3 become hypobiotic L4 and existing adults die off. at end of grazing season there is low egg count, low pasture contamination, and a lower worm burden than there was at the peak. by this point animals also more resistant so fewer eggs. the goal of parasite control : suppress worm burdens below levels at which economic losses occur. prevent buildup of infective larvae on pasture, because they translate into heavy worm burdens which produce clinical disease. you can ignore the animals and treat when diarrhea occurs - but this fails, because by the time they have the clinical signs of acute diarrhea, you already have a lot of infective L3 on pasture which came from the eggs made by the small worm burden they got when they first went onto pasture. if you treat at onset of signs you suppress egg counts briefly, but animals are reinfected immediately because pasture is so contaminated. so you need a parasite control program that prevents the problem. you have to anticipate the event. if you treat early, say about 5 wks after turning them out to pasture and again 3 wks later, you see there is a significant difference, but not enough to do the job. fewer eggs, but still many eggs, are being shed. BUT - if you use the wonder drug, ivermectin, three times, early in the season - about 3 wks after turn out, then a month later, and a month after that, you suppress the initial egg production by killing growing L4/L5/adults 3 wks post infection , preventing initial adult worm burden, preventing initial egg output - which prevents the later disease. you have to prevent this first egg output curve to prevent later problems. that's why you have to treat so early to get rid of the initial small adult worm burden. so you kill everything early , prevent big peak in egg production. interestingly, this pattern occurs regularly year to year. if you are lucky and you have available safe pasture that hasn't had infected animals on it for over a year, you can treat at the peak of the first egg curve, then move the animals - so they can't eat the L3 from the eggs they did produce. this will obviate the second two events - they aren't going to be ingesting more L3s, so they won't make large numbers of adults, and won't get sick. so 'treat and move' strategy makes sense biologically and epidemiologically - remove animals from source of infection. then they can't get infected. slow release bolus - paratect - a form of pyrantel - when this is placed in the rumen before turnout, you get a slow daily release of therapeutic dose. this will also suppress egg counts, L3, and adult worm burden. this is good to suppress infections, but the problem is that if you give animals therapeutic dose every day for three months, you encourage the resistance of drug resistant strains. after 2-3 seasons in europe, all the ostertagia in europe were resistant to pyrantel. anthelmintics for cattle: we had tables from dr G, now there is another one from dr j. highlights - important worms are:GI nematodes, arrested ostertagia L4, lungoworms, fasciola and monezia. drugs are: oxfendazole, fenbendazole, IVM, clorsulon which gets fasciola, doramectin, eprinomectin, and albendazole which also gets fasciola. most of these drugs will kill GI nematodes, lungworms, and ostertagia L4 (clorsulon only gets fasciola). only oxfendazole and albendazole get monezia, but that's not really a clinically significant parasite anyway. eprinomectin and doramectin - the new avomectins, are now available as pouron preparations - you just pour it onto the animal as they go through a chute. another reason they are popular is because they are also active against arthropods. they have a broad spectrum of activity. eprinomectin/eprimex is nice b/c when you pour it on to its back, if it is outside, it won't wash off. it gets taken up into sebaceous glands and follicles very rapidly. if animal gets wet, it's ok. with doramectin, it is slower to be absorbed, so it will wash off if it rains right away. also eprinomectin has no withdrawal time. the other avomectins have longer withdrawal times up to 30 days. ok. briefly - if parasite control of growing dairy cows and heifers is adequate, then control in adults should be unnecessary. we've gone over the arguments already. dictyocaulus viviparus - lung infections due to this are widespread. if drugs effective against it are incorporated into a program, it shouldn't be any kind of threat. in PA we only see outbreaks of lungworm in cattle in cooler parts of the state - poconos, north central area. when we see good outbreaks of it is when summer has been cooler and wetter than normal. dictyocaulus likes cooler conditions - more common in northern europe. not too common around philadelphia! more outbreaks in cooler parts of state. slide: open lung, with dictyocaulus viviparus in the bronchi - threads sitting in there, it looks like. fasciola hepatica - a bit like dictyocaulus in that distribution in terms of clinical dz is limited - based on snail intermediate hosts - gulf coast region and far west rocky mt area. in CA found in areas where there is a lot of irrigation. calves from these areas are commonly shipped to feedlots. good control is essential. moving on to - we already had sarcocystis with dr farrell - and we're going to skip beef cattle parasite control - so we won't have questions abou thtat on the exam - so we'll go on to sheep. sheep- GI nematodes include haemonchus, ostertagia, strongyloides lungworms tapeworms (monezia) coccidia consider the sheep of america - only about 10 million. TX has about 2 million, and IA has a lot of sheep farms. in PA there are about 135,000 sheep, down from all time high of 3 million in 1886. so sheep industry in US has stabilized at a low level after a steady decline over past 100 yrs. the industry consists of part time hobby farmers in the east. there isn't much money to be made unless you breed purebreds or occupy a niche market. for vets, there isn't a lot of money either, unless hobby farmers are wealthy and view sheep as pets, not production animals. see handout for extensive list of parasites in sheep. most important are GI nematodes haemonchus, trichostrongylus, ostertagia, strongyloides. less important are lungworms, monezia, and coccidia. around here, h.contortus is commonest and most important - b/c of bloodsucking. the others are not prevalent and are not that pathogenic, although they do contribute to economic losses due to subclinical effects. but, if you make a control program for hemonchus contortus it will control the rest of them,mostly. strongyloides papillosus is common in nonimmune nursing lambs. goats - major nematode pathogens of sheep are also the same in goats. some differences - few drugs are approved for use in goats, so when you use anthelmintics in goats it is an offlabel use, and the doses should approximate the doses for cattle, not sheep - cattle and goats metabolize the drugs more quickly than sheep do. all these nematodes have direct life cycles. eggs hatch, grow in environment to L3, then get eaten or penetrate in or whatever. in optimal conditions, L3 can develop in 2 wks. PPP is anywhere from 2-4 wks depending on spp of nematode. these nematodes have numerous adaptations to ensure survival and transmission, including hypobiosis, PPR in egg count, survival of some L3 on pasture over winter esp ostertagia, trichostrong, and nematodirus,and long adult life span of trichostrongylus. there are marked seasonal variations on these populations on pasture and in host. consider a ewe who lambs out in late winter, January. 6-8 wks later, she has a PPR which peaks at the time of weaning of lambs and then declines after weaning (eg, peaks in april or so). because of hormones esp prolactin, ewe is temporarily immunosuppressed, remember. so the arrested larvae within the ewe - previously arrested L4 become adults, make eggs - can do this because ewe is temporarily immunosuppressed. so ewes pump out large numbers of eggs. once weaning occurs, hormones drop off, egg counts drop off as immunosuppression is reversed, worm population is expelled - "self cure". so, now you have your weaned lambs, and they start grazing, and they will ingest the L3 that come from the eggs from the ewes. this pattern occurs regularly year to year, so we can predict and control it. so note that ewes are still ingesting lots of eggs - they are immune so they do not make a lot of eggs, but the lambs are making plenty of eggs. also, later in grazing season ewes may have really high worm burdens, so may produce some eggs. to recap: PPR (post parturient rise in nematode egg counts) comes from three sources. - there are always a small number of adult worms in GI tract . those are putting out a low number of eggs normally, but under immunosuppressive conditions they make more eggs. previously arrested L4 develop and new adults make eggs. and later, new nematodes are aquired from pasture, and new adults from there also produce eggs. in an immune host, we see the process of self cure - expulsion of adults. but because of post parturient relaxation of resistance, adults are not expelled - they survive for a while - and they pump out a lot of eggs onto the pasture, and now they will rapidly become L3s. if the lambs are then weaned, and left on pasture, with their mothers, the L3s will be eaten by the naive lambs, and they will grow into adults. lambs become heavily loaded with haemonchus. so you have to prevent the PPR to prevent this. this is a unique example of a parasite synchronizing its life cycle with host life cycle - lambs start grazing just when the L3s are peaking on the pastures, from eggs passed by their moms due to PPR. clearly this has evolved over many generations. key to control of parasites in sheep then is to eliminate arrested larvae. make sure they are killed so they do not become adults so PPR is not produced. two drugs do this: Levamisole and Ivermectin. Second strategy - treat lambs and move them to safe pasture. third thing - treat lambs with four spring/summer tx at 3 week intervals. these lambs are really vulnerable b/c they are immunologically naive. you don't need a heavy hemonchus burden to cause serious dz in young lambs. given 6 groups of lambs 1- tx four times with IVM during spring/summer. they stayed on contaminated pasture. av daily wt gain 0.168 kg, no deaths 2- IVM tx july 2nd, lambs moved to safe pasture. one death (before july 2nd). avg wt gain 0.183 kg 3. IVM 8 doses. stayed on contaminated pasture. wt gain 0.176 kg. no deaths 4. tbz 8 doses on contaminated pasture - 3 deaths, .115 kg 5. no tx- contaminated pasture - .115 kg, 2 deaths 6. no tx- safe pasture - 0.130 kg/day, no deaths so. most strains of haemonchus are resistant to the benzamidazoles. that's why the TBZ didn't work. note that you get better wt gain by treating only once and moving lambs to safe pasture. this shows that you don't necessarily have to use drugs willy nilly. you can employ certain strategies to account for life cycles of the parasite, to lessen the number of tx you give. note: lambs do not develop immunity to h.contortus until they are at least 6-9 mos old. --end---