Increased incidence of congenital malformations in children with transient thyroid-stimulating hormone elevation on neonatal screening.

We investigated the incidence of congenital malformation in all infants with raised thyroid-stimulating hormone (TSH) levels on neonatal screening in Scotland between August 1979 and December 1993. Of 344 infants with elevated TSH, 31 (9%) had one or more malformations: 12 cardiac 15 noncardiac, and 16 dysmorphic syndromes (including 5 with Down syndrome). Criteria were devised to distinguish between definite or probable congenital hypothyroidism and transient TSH elevation. Congenital hypothyroidism was considered definite in 224 (65.1%) infants and probable in 11 (3.2%). Eighty-eight (25.6%) infants had transient TSH elevation, whereas thyroid status was uncertain in 21 (6.1%). In the definite group 12 (5.4%) infants had one or more malformations compared with 13 (14.8%) in the transient group. Cardiac malformation, noncardiac malformation, dysmorphic syndromes, and "sickness" were much more frequent in the transient compared with the definite group: 5.7% versus 1.8%, 8.0% versus 1.8%, 6.8% versus 2.7%, and 37.5% versus 7.1%, respectively. The incidence of congenital malformation in bonafide congenital hypothyroidism is lower than has been previously reported. The high incidence of congenital malformation associated with transient TSH elevation indicates the need to reevaluate the diagnosis of hypothyroidism in all infants with TSH elevation and concurrent illness or malformation.

Control of naturally acquired bovine parasitic bronchitis and gastroenteritis with an oxfendazole pulse release device.

Four groups, each of six male Friesian calves, were set-stocked on separate 0.66 ha paddocks from May 7 until October 23 1986. Each of the animals in groups 1 and 4 was dosed with an oxfendazole pulse release bolus at turn out whereas the animals in groups 2 and 3 were left untreated. Parasite-free naive tracer calves were introduced into each paddock for a limited period 12 days after turn out and again at the end of the trial. No adverse reactions or clinical signs were observed in either of the groups of calves which received boluses. The development of clinical parasitic gastroenteritis in both the untreated groups necessitated the humane slaughter of two animals and emergency anthelmintic treatment of the remainder. The lower plasma pepsinogen concentrations, and lower faecal egg and larval counts and worm burdens post mortem, together with the absence of clinical signs of parasitic gastroenteritis and bronchitis in the treated calves, confirmed the high efficacy of the bolus treatment.

Oxfendazole pulse release intraruminal devices and bovine parasitic bronchitis: comparison of two control strategies in a field experiment.

Lungworm-infected seeder calves were used on two 1.41 ha paddocks to ensure that groups of 11 susceptible trial calves would be exposed to heavy early season challenge with Dictyocaulus viviparus. This produced conditions for an artificially severe test of two control strategies. The first employed a front-loaded oxfendazole pulse release bolus, ie, an intraruminal device which released one therapeutic anthelmintic dose immediately and five subsequent pulses at approximately three-weekly intervals. These front-loaded boluses were given to five of 11 calves on one paddock as soon as parasitic bronchitis had become clinically obvious (34 days after turnout) while the remaining six calves were kept as untreated controls. Clinical signs quickly subsided in the treated animals and no further respiratory problems occurred despite continued exposure to reinfection. The other control strategy involved the administration at turnout of an oxfendazole pulse release device which released the first of five anthelmintic doses approximately three weeks after administration, to all 11 calves on the other paddock. This strategy was almost completely successful in preventing patent infections from establishing and reduced the infectivity of the pasture in August and September by 94.1 per cent as shown by tracer calf studies. The calves treated at turnout performed better than the calves treated with the front-loaded boluses for most of the season and had an average weight-gain advantage of 20.4 kg at housing (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Anthelmintic evaluation of a thiabendazole-resistant strain of Ostertagia circumcincta recovered from sheep in England.

A total of 35 worm-free lambs were infected with a strain of Ostertagia circumcincta isolated earlier from sheep in Cheshire, England, and found to be resistant to thiabendazole (TBZ). When patency was established the sheep were divided into groups of six, and dosed orally with either TBZ (44 mg kg-1, 88 mg kg-1), fenbendazole (FBZ; 5 mg kg-1) or levamisole (7.5 mg kg-1) or not treated. Three of the remaining five animals were dosed with FBZ at 10 mg kg-1. Egg hatch tests, post-dosing faecal egg counts and post-mortem worm counts confirmed resistance to TBZ, and a degree of side-resistance to FBZ was also revealed. Only levamisole gave the clearance expected of modern anthelmintics.

Effect of repeated doses of levamisole on grazing cattle infected with Dictyocaulus viviparus.

Seventy-one worm-free Friesian calves were allocated by weight to three trial groups (1, 3 and 4) of 18 and a control group (2) of 17 animals. Calves in group 1 were vaccinated with a bovine lungworm oral vaccine on days 0 and 28, and on day 42 all groups were turned out to graze together on pasture known to be infected with Dictyocaulus viviparus larvae. Twenty-eight days after first exposure to infection one control calf died of parasitic bronchitis. Anthelmintic medication consisting of two doses of levamisole (7 . 5 mg/kg) at 14 day intervals was promptly administered to group 3 calves and three doses at the same intervals to group 4 calves. All calves were challenged with 20,000 infective D viviparus larvae on day 147. Calves were weighed every 14 days throughout the trial which ended 42 days after challenge. Pasture contamination and infectivity were monitored by pasture larval counts and tracer calves. Statistically there was no significant difference between the performances of treated and vaccinated groups before challenge but all were significantly superior to the control group. After challenge the productivity of all experimental groups was temporarily depressed but the levamisole treated cattle recovered more rapidly becoming significantly heavier than the vaccinates at the end of the trial. The mean group weight gains over the trial period were 89 . 92, 63 . 87, 88 . 67 and 98 . 70 kg in groups 1, 2, 3 and 4 respectively.

Comparison of protection against lungworm infection between levamisole-treated and vaccinated calves.

A trial involving 122 calves of approximately 100 kg bodyweight was undertaken to assess the protection against reinfection with Dictyocaulus viviparus in calves whose primary infection was treated with levamisole. Four matched groups, each of 20 housed calves, were taken and one group vaccinated against parasitic bronchitis. Calves in the remaining groups were infected with third stage D viviparus larvae daily for 42 days and treated with 7 . 5 mg/kg levamisole administered subcutaneously at 14, 14 and 28, or 14, 28 and 42 days. All groups were challenged with 10,000 larvae per call on day 49. Relevant control groups were maintained. Eight calves from each main group were slaughtered four weeks later and survivors retained until 20 weeks from the start of the experiment. Calves treated sequentially with two or three doses of levamisole at 14 day intervals while exposed to incoming infection approximated more closely to the performance of vaccinated cattle and were significantly better protected against challenge than those receiving one dose of levamisole only. Feed conversion was most efficient in vaccinated calves not exposed to the potentially lethal trickle infection. After the last levamisole treatment, vaccinated calves and those treated with three doses of levamisole at 14 day intervals were significantly heavier than calves receiving one dose of levamisole only. Vaccinated calves grew heavier than those receiving triple levamisole treatments until the time of challenge. Thereafter the triple levamisole treatment group improved and eventually grew heavier than the vaccinated animals.

Observations on the epidemiology of Dictyocaulus viviparus in north west England.

A five year ley pasture was used as a source of natural infection with Dictyocaulus viviparus for cattle in anthelmintic trials. Pasture larval counts, faecal larval counts of permanently grazing calves and lungworm burdens harboured by tracer calves were monitored in three grazing seasons to assess the pattern of infection. Carrier calves were introduced at the beginning of the grazing season in the first two years of the study but not in the third. In the fourth year the pasture was subdivided into two paddocks where overwintered infection with and without carrier infection were compared. A control paddock exposed to carrier infection but no overwintered infection was also monitored. Pasture larvae survived the winter but carrier infection appeared to make a larger contribution to pasture larval counts and the onset of parasitic bronchitis in susceptible calves. In the absence of grazing cattle at the end of the grazing season the concentration of D viviparus larvae on the herbage fell rapidly to undetectable levels. Discrepancies between contamination of herbage by infective D viviparus larvae and infectivity of pasture for susceptible cattle occurred in all years but were particularly marked on the third year when natural immunity appeared to influence the number of lungworms accumulating in tracer calves. Failure to recover lung worms from tracer calves cannot be regarded as an accurate indication of lungworm free pasture. In the first three years the proportion of the lungworm population which was inhibited in tracer calves was higher early and late in the grazing season and negligible in mid season. This suggests that a predisposition to inhibition in larvae which have overwintered on pasture may influence the time of onset of parasitic bronchitis in the next grazing season, but results from the fourth year did not support this hypothesis.

Protection developed against reinfection by Dictyocaulus viviparus following anthelmintic treatment of a one-day-old primary infection in cattle.

Single doses of 7.5 mg/kg levamisole subcutaneously and 5 mg/kg oxfendazole per os and three daily doses of diethylcarbamazine intramuscularly were 86.9, 82.1 and 46.6 per cent efficient, respectively, against one-day-old Dictyocaulus viviparus. These three dosage regimes were also associated, respectively, with 92.5, 36.4 and 56.0 per cent protection against reinfection following anthelmintic treatment. It is suggested that the high degree of protection following the use of levamisole may be a consequence of rapid and effective anthelmintic activity combined with immunomodulating effects.

Cell adherence to larvae of Dictyocaulus viviparus in vitro.

Bovine eosinophils survived for up to 48 hours in vitro in a medium of undiluted bovine serum and became adherent to the surface of Dictyocaulus viviparus larvae earlier than other cells found in peripheral blood. Cell adherence was associated with a heat labile factor in normal bovine serum and a heat stable factor in hyperimmune serum. A factor associated with leucocytes in vitro appeared to cause larval immobility. Cells from calves treated with levamisole behaved identically to those from other sources. It is suggested that eosinophils are an important element in host defence against D viviparus infection.

Speed of actin of some anthelmintics against Dictyocaulus viviparus infection in cattle.

In a study of the comparative speed of action of anthelmintics against Dictyocaulus viviparus infection in cattle levamisole reduced the lungworm burdens by 87 per cent within three hours of administration whereas fenbendazole and febantel required 36 hours to achieve 80 and 87 per cent reduction, respectively. The more rapid action of levamisole may be advantageous in the treatment of bovine parasitic bronchitis since it allows virtually immediate elimination of the majority of the lungworms and limits undesirable sequelae dependent on the continued presence of the parasite.