Parasitic Bronchitis and Pneumonia

Dwight D. Bowman

There is only a single lungworm, Dictyocaulus viviparus, that matures to the adult stage within the lungs of cattle. In sheep, the three main lungworms that may occur are Dictyocaulus filaria, Muellerius capillaris, and Protostrongylus rufescens; some other species mature in the lungs of sheep and goats around the world, but they are fairly rare compared to these other species.

Lungworms of Cattle: Dictyocaulus viviparus

■ Definition and Etiology Dictyocaulus viviparus is a trichostrongylid nematode that is found in the bovine trachea and bronchi. These are robust white worms that can reach lengths of 8 cm; the slightly smaller males have very dark brown, stubby spicules that can often be visualized within the body of the worm just anterior to the copulatory bursa. The life cycle of D. viviparus is direct. The female produces larvated eggs that hatch in the lungs, and the larvae make their way up the respiratory tract, are coughed up, and are swallowed to be passed in the feces. The larvae on pasture ultimately develop to an infective third stage without feeding and can develop in the laboratory in aerated water into doubly sheathed infective stages. The larvae take 5 days or longer, depending on environmental conditions, to develop to the infective stage on pasture.

■ Clinical Signs and Differential Diagnosis Primary infection with D. viviparus can be broken down clinically into a prepatent phase, a patent phase, and a postpatent phase.³ No signs are associated with the initial penetration of larvae until they reach the alveoli, where they provoke an eosinophilic exudate that blocks small airways. During the prepatent phase (approximately 7 to 25 days after ingestion) there is a gradual onset of coughing and tachypnea (35 to 60 breaths/min), which becomes increasingly apparent from day 14 to day 25. The severity of signs in this stage is proportional to the number of larvae ingested, the rate of ingestion, and the proportion of larvae reaching the lungs. Severe illness and death can occur in cases of heavy infection. In the patent phase (approximately 25 to 55 days after ingestion) a parasitic pneumonia with consolidation develops in the ventral areas of the caudal lung lobes as a result of aspiration of eggs and larvae into these areas.

Recovery begins in the late patent phase, and the signs gradually resolve, sometimes over several months. During the postpatent phase (about days 55 to 90), adult parasites are expelled by a self-cure phenomenon. In approximately 25% of severe cases the postpatent phase is characterized by a sudden exacerbation of dyspnea at days 45 to 60 that is often fatal, after secondary bacterial infection or alveolar epithelialization.^1,3 The reinfection syndrome occurs 14 to 16 days after adult cattle are placed on heavily contaminated pastures. Signs include acute hypogalactia; severe, frequent coughing; marked tachy­pnea; and depression. Auscultation reveals only harsh breath sounds with no crackles or wheezes.^1,3

Relative to D. viviparus, an ancillary finding occurred as part of a 3-year study in Sweden that examined the effects of different parasite control strategies administered to cattle during their first grazing season on their weight gain in the three second grazing seasons when they were all handled equivalently.⁴ Basically, during the second season of grazing, deficits acquired within each management group in the first year were maintained during the second year, but the first season of treatment had no effect on weight gain in the second season. During the second and third second-season grazing periods, D. viviparus entered the groups when additional contaminated pastureland was added to the grazing area in the final 2 years.

Differential diagnosis should be straightforward if both clinical signs and epidemiologic characteristics of the disease are taken into account, especially in endemic areas. This is a disease of groups of cattle at pasture, typically in late summer or fall in northern temperate climates; the situation thus resembles ABPEE, which differs in clinical signs (i.e., less coughing and fewer adventitious lung sounds). The signs associated with lungworm infection are reminiscent of those of farmer's lung, which occurs in quite different circumstances. In typically nonendemic areas, outbreaks associated with climatic changes are frequently mistaken for acute bacterial bronchopneumonia.¹

■ Diagnosis Classically, diagnosis has been through the detection of the characteristic larvae passed in the feces. In cattle, this is the only nematode parasite routinely producing larvae found in the feces, and thus if the fecal sample is fresh, the finding of larvae is fairly diagnostic. Rectal fecal samples are preferred for parasite examination because samples picked up off the ground may contain free-living nematodes that can be difficult to differentiate from lungworm larvae. Recovery of larvae from fecal samples is substantially diminished if the sample is stored at room temperature for more than a few hours. The larvae are best detected by the Baermann test⁵ and may be seen on a transtracheal wash. The larvae themselves are large (390 to 450 μm ? 25 μm), have a somewhat pointed tail (compared to Dictyocaulus filaria of the sheep), and have an intestine filled with dark granules.

In Europe, ELISA technology that is based on an antigen that is a recombinant product representing a major sperm protein of the adult male has now been developed to detect antibody in the milk and serum of cattle.^9-11 Examination in experimentally infected dairy cows revealed that the ELISA detected antibodies in the serum and milk some 30 to 32 days after infection and remained elevated for 112 to 138 days post exposure even though the cows had been treated for their infections with eprinomectin 49 days after infection and had ceased larval shedding.¹¹ However, if the cattle were treated during the prepatent period, larvae were never shed in the feces, and the animals remained antibody negative. This technique has now been adapted to determine the presence of antibodies in bulk milk and has been used to collect epide­miologic data. Of 810 dairy farms in Germany that were tested in January, September, and November, some 18% were positive on one occasion, and most positive samples were detected in January.⁹ It was not known what percentage of zero-grazing herds were included in the bulk milk samples.

■ Pathophysiology Once the fourth-stage larvae enter the alveoli, they incite an eosinophilic exudate that blocks small bronchi and bronchioles, resulting in atelectasis and causing the cough and tachypnea of the prepatent phase. As these larvae mature and migrate up the airways, these lesions may resolve. However, the adult worms produce an inflam­matory response in the larger airways, and aspirated eggs and larvae cause a marked macrophage and giant cell response, with consolidation of the ventral caudal lobes; these lesions are the cause of the signs in the patent phase. At any point in the pathogenesis (prepatent, patent, or postpatent stage), complications may occur that account for acute exacerbation and death. These complications are as follows:

• Development of pulmonary edema caused either by heart failure or by extensive alveolar epithelial damage and hyaline membrane formation

• Severe interstitial emphysema from the severe dyspnea

• Alveolar epithelial hyperplasia

• Secondary bacterial infection, which is relatively uncommon

In the reinfection syndrome, the immune response cannot completely overcome a massive challenge, and a small number of larvae reach the lungs. The signs are caused by the immune reaction to the migrating larvae. Lymphoid nodules develop around dead larvae in the bronchioles.^1-3

■ Epidemiology Parasitic bronchitis and pneumonia in cattle occur most often in temperate areas with high rainfall or intense irrigation. In the United States, lungworm infection is widely distributed, but disease outbreaks are uncommon, probably because periods of dry summer weather limit larval survival and accumulation on pasture.² In the southern United States, lungworm transmission is probably greatest in the cool winter months,¹² whereas autumn is probably the season of most intense transmission in the northern United States.^13,14

Dictyocaulus infections have been studied extensively in Europe, where the parasite is an important pathogen. Disease outbreaks occur most frequently in first season grazing animals. If large numbers of larvae are present on pasture at spring turnout of calves, disease may develop at that time. Often, however, levels of pasture larvae are too low to cause disease but lead to low-level primary infections in calves that result in the accumulation of additional larvae on pasture. This second wave of infection may lead to clinical lungworm disease when the primary infection did not produce adequate levels of immunity. If infection levels remain low, disease may not be observed until a third generation of parasites occurs. Immunity develops beginning about 10 days after heavy infection, and patent infections usually persist for only a few months. In the absence of continued exposure to parasites, immunity to reinfection will begin to decline after several months.^2,15

Older animals without immunity also develop lungworm disease when exposed to high levels of pasture contamination with larvae. This can occur when animals from a nonendemic area are moved to an endemic area. In recent years outbreaks of primary parasitic bronchitis have become an important cause of respiratory disease in adult dairy cows in Europe. The increased prevalence of disease in this older age-group is likely the result of decreased levels of immunity after the widespread use of powerful suppressive anthelmintic regimens in first and second season grazing animals. Other management factors, such as isolation of calves from adult carrier animals and increased movement of livestock, may also contribute to a decline in levels of immunity.^7,16 Beef animals are less often affected than dairy cattle because management practices are more extensive and levels of infective larvae on pastures are generally lower.² The reinfection syndrome occurs in immune adult animals when, for example, immune cows are placed on a pasture previously contaminated very heavily by calves with 12

patent disease.^1,2

In northern temperate climates, the infection is carried from year to year by overwintering of larvae on pasture in some areas, by spreading of manure from infected housed calves in the spring, and by carrier cattle. Lungworm larvae also may be inhibited in the lungs of calves in winter (as with Ostertagia species in the abomasum) and mature in the spring.^1,3 It appears that over the last decade the disease is becoming more common in the more northern parts of the United Kingdom.¹⁷

■ Necropsy Findings In the prepatent phase the lungs are largely normal, with a few atelectatic lobules in the ventral caudal lobes; adult worms are not present until late in this phase, but larvae may be detectable by microscopic examination of smears of bronchial exudate. In the patent phase there is usually bilaterally symmetric red consolidation of the ventral caudal lobes. Adult worms can be recognized on necropsy by their relatively large size and location in the trachea and bronchi. The lesions of the postpatent phase are similar, but no adult worms or larvae are present. In those patients that die of an acute exacerbation, there is extensive pulmonary edema and emphysema, with hyaline membranes and alveolar epithelial hyperplasia.

In the reinfection syndrome the pulmonary lymphoid nodules may be 3 to 4 mm in diameter and thus grossly visible as raised, gray-red to greenish-yellow nodules under the pleura. Initially these are composed of a core of eosinophilic parasitic debris surrounded by macrophages, multinucleated giant cells, hyperplastic bronchiolar epithelium, eosinophils, and plasma cells. The lesions eventually mature to lymphoreticular nodules with a germinal center. There is also greenish mucus in the airways and a greenish discoloration to the tissues, both caused by eosinophil infiltration. There is no edema or emphysema, and the rare lungworms that may be found are small and stunted.¹

■ Treatment, Prognosis, Prevention, and Control D. viviparus infection can be treated with a number of bovine anthelmintics available in the United States and other countries (Table 31.16). Macrocyclic lactone products also have residual efficacy against D. viviparus, and there is now an extended- release eprinomectin compound that will provide protection for 150 days.^18,19 Animals with only cough and tachypnea respond well, whereas those with dyspnea, fever, anorexia, and depression have a more guarded prognosis; some of these animals can be expected to die or remain chronically unthrifty.¹ Control (see also Chapter 49) involves appropriate pasture management and the strategic use of anthelmintics to prevent buildup of infection in the herd and on pastures. Several strategic deworming programs that effectively suppress lungworm infection throughout the grazing season have been developed in Europe. These programs include use of ivermectin at 3, 8, and 13 weeks after turnout and use of doramectin or eprino- mectin at 0 and 8 weeks. Use of an oxfendazole pulse release bolus (not available in the United States) also provides strategic treatments. Alternatively, use of a continuous-release ivermectin or fenbendazole bolus (not available in the United States) will prevent development of lungworm infection during its period of efficacy.¹⁶ A long-acting moxidectin injection product that provides protection from lungworm infection for 120 days is also now available in some countries.²⁰ Anthelmintic treatment with moxidectin or fenbendazole followed by movement of calves to safe pasture 9 weeks after turnout was also effective in controlling lungworm.²¹ None of these control programs has been extensively tested under the variety of grazing condi­tions found in the United States.

■ Table 31.16

Anthelmintics Approved for Treatment of Dictyocaulus viviparus in the United States

Despite concern that suppressive programs may limit exposure to larvae and interfere with the development of immunity to lungworm, several studies conducted in Europe have shown that stimulation of the immune response still occurs, although relative levels of immunity may vary with different management systems and annual variation in the intensity of lungworm challenge.^7,22-24 In Europe, methods of control also include an effective irradiated larval vaccine.

Delay of spring turnout is an adjunct to control but should not be relied on as the sole means of control.²³ A targeted selective deworming program was successful in controlling lungworm infection in a dairy herd in Sweden. Only cattle testing positive for lungworm by the commercial ELISA were treated at each sampling date.²⁵ In an attempt to eradicate D. viviparous from two farms in the Netherlands that had had lungworm-associated disease outbreaks, both herds were mass treated with eprinomectin at turnout.²⁶ From August to November of the first year after treatment, all first-year heifers remained lungworm negative as determined both by fecal examination and by monitoring for D. viviparus-specific antibodies. However, in the second year after treatment, one of the herds developed signs of parasitic bronchitis that was confirmed serologically. The other herd remained negative until at least the fourth year after treatment, but then signs of parasitic bronchitis were observed and the cattle were treated. The authors of this report believed that in both cases the D. viviparous was reintroduced into the herd from an outside source or perhaps that the reuse of pastures that may have lain fallow for an extended period provided the source of the new infections.

TOXOCARA Vitulorum. This parasite seems to be reemerg­ing in prevalence within the developed world; there have been recent reports from a bison herd in western Canada, suckling beef calves in the Netherlands, and suckling Simmental cattle in the United Kingdom. In a closed cow-calf beef operation in north-central Florida, 17.6% of 105 calves under 3 months of age were found to be infected, and on a beef farm in Iowa, 40% of 34 calves were found to be infected after a calf died due to an ascarid intestinal impaction.^27-30 Infections in neonatal calves are acquired by fairly large larvae (0.75 to 1.5 mm in length) that are passed from cow to calf in the milk. In cows that ingest eggs, the larvae undergo a liver-lung migration before they make their way to the various tissues of the cow, where they are known to persist for at least 5 months.³¹ There typically do not appear to be any signs associated with the lung migration of the larvae, but repeated passage of the larvae through the lungs on contaminated pasture could perhaps produce respiratory signs in older calves or adult animals.

ASCARIS SUUM. Cattle exposed to large numbers of A. suum eggs in areas contaminated by swine may have an interstitial pneumonia. Animals are typically affected approximately 10 days after exposure. Signs include depression, anorexia, fever, tachycardia, tachypnea, dyspnea with an expiratory grunt, variable coughing, ruminal stasis, and bloat. Auscultation of the lungs reveals increased breath sounds without adventitious sounds. Some deaths may occur. Differential diagnosis is difficult. Differentiation from the other interstitial pneumonias depends more on history of exposure to the causative agents (e.g., lush pastures, sweet potatoes moldy with Fusarium solani, wild mint, Perilla frutescens, toxic gases, moldy hay). Differentia­tion from viral pneumonia (such as that caused by BRSV) and D. viviparus reinfection syndrome requires necropsy and demonstration of larvae. Ascarid larvae have characteristic lateral alae in histologic sections. Patent D. viviparus infection can be differentiated by Baermann examination of the feces. In fatal cases the lung lobes are firm and mottled blue, red, and gray. The cut surface oozes thin yellow exudate. There is emphysema in the dorsal diaphragmatic lobes and subpleural hemorrhage with neutrophil infiltration and necrosis of bronchiolar and alveolar epithelium. In chronic cases the cellular infiltrate is lymphocytic, and there is proliferation of bronchiolar epithelium and peribronchial fibrosis. Recommended treatments include corticosteroids (dexamethasone, 0.04 mg/kg IM or IV or prednisolone, 1 mg/kg IM or IV daily) and antibiotics to control secondary bacterial infection.³² Clinical signs resolved after treatment with oxfendazole in one outbreak of suspected A. suum migration.³³ Cattle should not be exposed to areas heavily contaminated by swine.

Lungworms of Sheep and Goats

Three species of lungworms are of primary importance in sheep and goats: D. filaria and the two metastrongylid nematodes, M. capillaris and P rufescens. Other genera of metastrongylid lungworms of minor pathogenic importance in sheep and goats include Cystocaulus, Spiculocaulus, and Neostrongylus. These parasites are rare or absent in North America.³⁴

DICTYOCAULUS FILARIA. D. filaria has a life cycle essentially identical to that of D. viviparus; the time from ingestion to the appearance of larvae in the feces is about 4 weeks. Mainly young animals are affected, but disease can also occur in adults. Dyspnea, tachypnea and coughing, and loss of condition occur in clinical cases.^32,33 Differential diagnosis includes the progres­sive viral pneumonias. Diagnosis is made by finding larvae in fresh feces by the Baermann test.⁵ Samples should be tested soon after collection because larval recovery is significantly reduced in stored samples.⁶ Larvae of D. filaria are similar in size and appearance to those of D. viviparus but also have a distinctive knob on the anterior end. The pathogenesis is similar to that of D. viviparus (see earlier discussion). The adults are found largely in the dorsal-caudal regions of the diaphragmatic lobes. Bronchitis and peribronchitis, along with cone-shaped areas of pneumonia and atelectasis, and emphysema are present. Secondary bacterial infections may also occur.^34,35 Levamisole (8 mg/kg), fenbendazole (5 to 10 mg/kg), ivermectin (0.2 mg/ kg PO),'³³ and moxidectin (0.2 mg/kg PO or SC)^36-38 can be used for treatment. When outbreaks occur, all animals should be treated and moved to fresh pasture when possible. Clinical D. filaria infections seem to occur most frequently in areas with warm climates. In temperate areas the parasite overwinters either as arrested larvae in ewes or as larvae on pasture.³⁴

MUELLERIUS CAPILLARIS. M. capillaris is probably the most common of the lungworms of sheep and goats. Infection is more pathogenic in goats than in sheep. Surveys in Maryland and Georgia detected the parasite in 64% and 68% of goats, respectively.^39,40 The life cycle is indirect. First-stage larvae are coughed up, swallowed, and passed in the feces. These larvae are relatively resistant and may survive for several months in the environment. After penetration of an appropriate mol- luscan intermediate host, the infective third stage develops in a minimum of about 12 days, is ingested with the snail, and passes to the mesenteric lymph nodes. The fourth-stage larvae proceed to the lungs, where adults develop in the alveoli. The prepatent period of M. capillaris infection is about 6 weeks.⁴¹ Although many infections are subclinical, clinical disease may develop. Goats appear to be more likely than sheep to develop unthrifti­ness, coughing, and dyspnea. Infection may also predispose to secondary bacterial infection.⁴⁰ The difference in clinical signs between sheep and goats probably results from a difference in the pathogenesis of infection. The adult worms live in the pulmonary parenchyma, particularly the subpleural tissue. In sheep they produce grayish nodules typically 2 to 3 mm in diameter. On palpation at necropsy, these nodules have been described as feeling like “lead shot.”⁴⁰ Each nodule contains a worm and necrotic leukocytes and pulmonary tissue sur­rounded by a connective tissue wall and giant cells.³⁴ They may calcify or become secondarily infected with bacteria. Reports of lesions in goats indicate that M. capillaris causes an interstitial pneumonia. The lungs are resilient and firm, fail to collapse, and have tan, yellow, or gray patches located especially in the dorsal diaphragmatic lobes. The histologic lesion in goats is a diffuse thickening of alveolar septa, with a mononuclear cell infiltrate and alveolar epithelial hyperplasia that extends far beyond the area immediately around the parasite. The local reaction around the worm is quite variable and does not appear to produce the nodules seen in sheep.⁴² Diagnosis is made by Baermann examination of the feces. The larvae are smaller than those of D. filaria and have a kink at the end of the tail with a characteristic subterminal accessory spine.⁵

Several anthelmintics have been used in the treatment of M. capillaris infections. Moxidectin (0.2 mg/kg in oral or injectable formulation) is effective in treating sheep infected with M. capillaris and other small lungworms (Cystocaulus ocreatus, Neostrongylus linearis, and P. rufescens) and may be equally effective in goats.⁴³ Although larvae may initially disappear in the feces after treatment, they often reappear in fecal samples again after 1 to 2 months because anthelmintics are ineffective against immature worms and/or because inhibited larvae resume development.⁵ Treatments that appear to eliminate adult parasites in goats include fenbendazole (15 to 30 mg/kg),^41,42,44-47 albendazole (10 mg/kg),⁵⁶² oxfendazole (7.5 to 10 mg/kg),⁵⁶³ and ivermectin (0.3 mg/kg).^44,48 M. capillaris is largely resistant to levamisole.³⁵ Better control of immature or inhibited larvae with fenbendazole was achieved by administering the drug (1.25 to 5 mg/kg) for 7 to 14 days, although a regimen of 1 week on/1 week off/1 week on appeared to provide the most effective treatment. Albendazole (1 mg/kg PO daily for 7 to 14 days) was also effective.⁴⁶ Possible teratogenic effects of extended benzimidazole treatment in goats have not been thoroughly investigated, and albendazole should be used cau­tiously in the first 35 days of pregnancy.⁴⁴ Administration of ivermectin (0.3 mg/kg) or fenbendazole (15 mg/kg) two or three times at 35-day intervals has also been suggested for treatment.³⁵ Control methods include avoiding wet pastures and treating animals before the start of the grazing season to reduce infection levels in the intermediate host.³⁵

Protostrongylus rufescens. p rufescens also uses molluscan intermediate hosts, and adults develop in the small bronchioles of sheep and goats.⁴¹ Most infections are probably subclinical or produce only mild signs of chronic bronchitis or bronchopneumonia with nasal discharge and cough. Occa­sionally P. rufescens may produce severe or even fatal disease.⁴⁷ The diagnosis of Protostrongylus spp. infection is made by finding larvae in the feces with the Baermann technique. The larvae are similar to those of Muellerius except that Protostrongylus larvae lack the subterminal accessory spine on the tail.⁵ Fen­bendazole, levamisole,⁴⁹ and moxidectin⁴³ can be used for treatment at the dosages used for Dictyocaulus. Other macrocyclic lactone products also may be effective but have not been tested. Control strategies are identical to those for M. capillaris. Few cases of infection have been reported in the United States, but nonspecific clinical signs, presence of subclinical carriers, and need for a special diagnostic technique may produce an underestimation of the prevalence of P rufescens infection in sheep and goats.⁴⁹

LARVAL TOXOCARIASIS. The dog ascaridoid Toxocara canis will infect and persist in the tissues of sheep and goats following the ingestion of infective eggs from pasture.^50-52 Migration of the larvae through the lungs does result in diffuse pulmonary inflammation, but there do not seem to be any clinical pul­monary signs accompanying the experimental infections.^53,54 Examination of sheep serologically using antibody detection tests has revealed that the prevalence of infection increases with age, with overall prevalences being 50% or more in the older animals sampled in Wales and Brazil.^55,56 More recent reports have found high levels of antibodies to T. canis in sheep from Brazil, Mexico, and Greece, and the report from Greece indicated that the seroprevalence in sheep was 7.71-fold higher than that found in goats from the same area.^57-59