Efficacy of halofuginone lactate in the prevention of cryptosporidiosis in suckling calves

The efficacy of halofuginone lactate in the prevention of cryptosporidiosis in suckling calves was evaluated in a multicentre, control versus placebo, randomised, double-blind clinical trial. Seventy-eight six- to 48-hour-old calves were treated daily with 120 microg/kg bodyweight of halofuginone lactate administered orally for seven consecutive days, while 80 calves received a placebo. Faecal samples were collected on the first day of dosing and four, seven, 14 and 21 days later, and Cryptosporidium parvum oocysts were counted and faecal indices for diarrhoea were determined after a clinical examination. An analysis of variance for repeated measurements showed a highly significant difference in favour of halofuginone lactate for both the oocyst counts (P=0.0002) and the faecal diarrhoea indices (P=0.0001) throughout the trial. The difference was greatest after seven days, when the mean oocyst count of the placebo group was 2.5 times and its mean faecal index was twice the mean of the halofuginone lactate group. One day after the end of the treatment the calves which received halofuginone lactate excreted 44 per cent fewer C parvum oocysts and 44 per cent fewer of them had diarrhoea. The reduction was even greater (65 per cent) when liquid diarrhoea was assessed, with 32.5 per cent of the calves in the placebo group having liquid diarrhoea compared with 11.5 per cent in the halofuginone lactate group. The treatment was well tolerated and easily administered.     

Controlling the onset of natural cryptosporidiosis in calves with paromomycin sulphate

A prospective, controlled-blind field trial was conducted to evaluate the efficacy and safety of paromomycin sulphate, given for 10 days from birth, in preventing natural cryptosporidiosis in calves. In the untreated control group, oocyst shedding and diarrhoea followed the pattern that had occurred on the farm before the trial, consistent with a perinatal infection, whereas in the treated group, the prepatent period was significantly longer than in the control group (P < 0.01) and oocyst shedding and diarrhoea started only after the drug was withdrawn. However, the regimen did not reduce the incidence of disease in the treated group.     

Chemotherapeutic efficacy of sulphadimidine, amprolium, halofuginone and chloroquine phosphate in experimental Eimeria bareillyi coccidiosis of buffaloes

Sulphadimidine, amprolium, halofuginone and chloroquine phosphate were administered to buffalo calves 10 days after experimental infection with Eimeria bareillyi. Animals given sulphadimidine or amprolium remained clinically normal and shed only a few oocysts in their faeces. Halofuginone was found partially effective and chloroquine phosphate completely ineffective in preventing faecal oocyst discharge and intestinal lesions. Sulphadimidine and amprolium treated calves gained weight, but chloroquine treated calves suffered progressive weight loss similar to that of infected untreated controls. No significant alterations of haematological values were observed either in the treated calves or in the untreated controls.     

Prevalence and control of bovine cryptosporidiosis in German dairy herds

In a 5-year survey regarding its prevalence and importance in five German state veterinary laboratories Cryptosporidium was diagnosed annually in 19-36% of faecal samples either submitted to the laboratories or taken post mortem. In approximately half of the cases no other enteropathogens were detected. However, only 73% of 30 laboratories participating in a questionnaire survey routinely tested for this parasite, and the majority of researchers considered cryptosporidiosis to be of minor importance. In a placebo-controlled field study 152 suckling calves were treated daily against cryptosporidiosis either with sulfadimidine or with halofuginone (Halocur, Intervet) over 1 week. Treatment by oral drench started at the onset of diarrhoea in the herd. Oocyst excretion, faecal consistency and health status were recorded five times for a 3-week period. Oocyst excretion peaked 7-14 days in the placebo group after the onset of diarrhoea, and during that period prevalence and intensity of excretion were significantly lower in the halofuginone-treated group compared to the sulfadimidine and the placebo control groups. The health status (diarrhoea, dehydration) declined in all groups but was significantly (P<0.05-0.001) better in the halofuginone group in the first 2 weeks. Halofuginone effectively (P<0.05-0.001) reduced oocyst excretion and improved the health status of the treated animals, while sulfadimidine had no effect against Cryptosporidium.     

Efficacy of azithromycin dihydrate in treatment of cryptosporidiosis in naturally infected dairy calves

The objective of this study was to evaluate the therapeutic efficacy of azithromycin treatment of cryptosporidiosis in naturally infected calves under field conditions. Fifty Holstein calves with cryptosporidiosis infection were divided into 5 groups: 1 group (10 calves) was unmedicated and served as the control group and was given distilled water only, whereas the other groups (10 animals per group) were medicated orally with azithromycin at the doses of 500 (group 1), 1,000 (group 2), 1,500 (group 3), and 2,000 mg (group 4) PO once daily for 7 days. The animals were examined clinically and fecal samples were collected on the 1st (inclusion day), 7th, 14th, and 21st days of the study. Drug efficacy was assessed by evaluating diarrhea, oocyst shedding, and weight gains from days 1 to 21 (4 assessments). Significant differences were observed in reductions of oocyst shedding (P < .05) and the fecal diarrhea incidence (P < .05) in groups 3 and 4 when compared with groups 1 and 2 and the control group. Weight gain of medicated calves was significantly higher than that of the unmedicated calves throughout the study (P < .05). The drug significantly suppressed oocyst shedding and resulted in significant improvements in clinical signs. Therefore, this suppression may have significant effect on the reduction of environmental contamination by cryptosporidial oocysts. From the economic point view, authors suggest that the most effective dose of azithromycin for the treatment of cryptosporidiosis in calves should be at 1,500 mg/d for 7 days.     

Chemoprophylaxis of coccidiosis in lambs with a single oral dose of toltrazuril

The prophylactic efficacy of a single oral dose of toltrazuril against coccidiosis (mixed Eimeria infections) in naturally infected lambs was evaluated in two experiments. Toltrazuril at 20 mg kg-1, given on Day 7 or Day 10 after turnout on pasture, proved to be highly efficacious in preventing clinical coccidiosis under Norwegian conditions. Toltrazuril reduced the oocyst output to very low levels, prevented the development of diarrhoea and improved weight gain during the first 4-5 weeks after treatment. Treatment on Day 7 was superior to treatment on Day 10 with respect to improving weight gain and preventing the development of soft faeces. Lambs treated with toltrazuril on Day 7 seemed to be as immune as untreated lambs to natural reinfections with coccidia later in the grazing season. In one of the experiments, natural infections with the nematode Nematodirus battus produced a coccidiosis-like disease in some lambs simultaneously with the outbreak of coccidiosis.     

Immunization protocols against Cryptosporidium parvum in ovines: protection in suckling lambs

Ovine colostrum and milk from immunized ewes were tested for their ability to prevent cryptosporidiosis in the lambs experimentally infected with 10(6) oocysts of Cryptosporidium parvum at 36-48 h of age (day 0 post-infection). All lambs became infected and developed clinical cryptosporidiosis. However, lambs fed by immunized dams have shown shedding involved, significantly, fewer oocysts and lasted for a shorter period than in control lambs. In addition, diarrhoea was less severe. The best results emerged in lambs of ewes immunized by intramuscular injection of an emulsion of 2 ml of Freund's complete adjuvant and 2 ml of C. parvum antigen in sterile phosphate buffered saline solution, administrated four weeks before parturition, together with an intramammary infusion of 25 microg of antigen in 2 ml of sterile PBS emulsified in 2 ml of Freund's incomplete adjuvant, which showed the highest anti-C. parvum titres in lacteal secretions. In their case, the onset of output of oocysts was delayed by two days, the patent period was shortened by three days, their diarrhoea continued for only three days, and the quantity of oocysts shed decreased by 77%. The outcome was that at the end of the study they had a live weight gain of 2 kg more than the lambs in the control group. These results indicate that lactogenic immunoprophylaxis should help mitigate the financial losses caused by cryptosporidiosis in small ruminants, as well as reducing the risk of infection of humans through the decreased contamination of the environment with oocysts.     

Activity of an anti-inflammatory drug against cryptosporidiosis in neonatal lambs

The efficacy of the anti-inflammatory drug Bobel-24 against experimental infection by Cryptosporidium parvum was evaluated in neonatal lambs. The animals were treated by oral administration of the drug at 50 or 500 mg/kg of body weight. The prophylactic/therapeutic treatment was started 4 h before inoculation of the lambs with oocysts and was continued for eight consecutive days. The therapeutic treatment was initiated at the onset of diarrhoea, after confirmation of infection, and was continued for six consecutive days. Infection was monitored by daily examination of faecal samples from the first day until 30 days post-inoculation. The criteria considered in evaluating development of the infection and the drug activity were: oocyst shedding, presence of diarrhoea and weight gain at 15 and 30 days post-inoculation. Bobel-24 was effective as a prophylactic/therapeutic treatment at the lowest dose (50 mg/kg of body weight); in the group treated with this dose of drug there was a longer prepatent period, a shorter patent period and a lower intensity of oocyst excretion than in the untreated control group, and the differences were all statistically significant (P<0.05). Moreover, one animal did not excrete oocysts, and two lambs had diarrhoea, for only 1 and 2 days. In the group treated with the higher dose of the drug, the diarrhoea lasted for a significantly shorter period (P<0.05) than in the untreated group.     

硝唑尼特抗免疫抑制小鼠隐孢子虫活性试验

研究硝唑尼特抗隐孢子虫的活性,采用地塞米松抑制昆明鼠免疫功能,经口接种感染微小隐孢子虫孢子化卵囊,成功制备出微小隐孢子虫感染的动物模型。将感染微小隐孢子虫的小鼠随机分为感染对照组以及高、中、低剂量3个药物剂量组,连续经口灌服硝唑尼特治疗1周,观察每只小鼠每天排出微小隐孢子虫卵囊的数量,以感染抑制率来评价硝唑尼特抗微小隐孢子虫的活性。结果表明,200 mg/(kg.d)剂量组能显著减少小鼠排出隐孢子虫卵囊的数量,对治疗微小隐孢子虫感染具有较好的疗效。     

Diarrhoea associated with cryptosporidial oocyst shedding in a quarterhorse stallion

Cryptosporidial oocyst shedding was detected in a 2.5-year-old Quarterhorse stallion with diarrhoea. Based on the detection of cryptosporidial oocysts, and the absence of other aetiological agents or enteropathogens, cryptosporidiosis was presumptively diagnosed. This case was unusual because cryptosporidial oocyst shedding is primarily found in some immunocompromised or immature horses, and has not been reported in healthy mature horses.     

Anticoccidial activity of arprinocid and halofuginone

Halofuginone and arprinocid, new anticoccidial drugs, were tested to determine the time of peak activity in the life cycle of Eimeria and whether they were coccidiocidal or coccidiostatic.Halofuginone was completely effective if medication was initiated by Day 3 postinoculation, but only partly effective if given on Days 4–7. Arprinocid was effective if given on Days 2–7 postinoculation, but only partly effective if given on Days 3–7. When medication was started on Day 0 and withdrawn on various subsequent days, good activity was recorded with halofuginone if the drug was given up to Day 1 postinoculation, but arprinocid required feeding up to Day 4 postinoculation.In other studies, medication was given until Days 6 or 7 postinoculation, then discontinued, to allow further development of coccidia that were arrested by the drug. With halofuginone, the oocyst passage was low with E. tenella and E. maxima, but moderate with E. mivati. With arprinocid, oocyst passage was low with E. maxima and E. mivati but moderate with E. tenella.These results suggest that halofuginone is active over a broader part of the life cycle than arprinocid, but both drugs had a predominantly coccidiocidal action.     

Observations and immunohistochemical detection of Coronavirus, Cryptosporidium parvum and Giardia intestinalis in neonatal diarrhoea in lambs and kids

In this study, clinical, parasitological, macroscopical, histopathological and immunohistochemical examinations were performed on 19 kids and 11 lambs (30 animals) with neonatal diarrhoea to detect the presence of Coronavirus, Cryptosporidium parvum and Giardia intestinalis. Clinically, severe dehydration, yellowish-green to brown coloured diarrhoea and death were observed. Mortality rates were 10-30% in the examined flocks. The most common agent was C. parvum diagnosed in 20 animals as a single causative agent, whereas G. intestinalis was found in 5 of 30 animals. These two protozoa were detected together in 4 animals upon faeces examination. Fifteen of 24 cases of C. parvum and 3 of 11 cases of G. intestinalis were also confirmed histopathologically. Following immunohistochemical examination, all cryptosporidiosis cases were confirmed by positive immunostaining of intestinal sections. Two additional Giardiosis cases with negative results upon parasitological and histopathological examinations were diagnosed by means of immunohistochemical examination. Coronavirus was detected immunohistochemically in one kid with neonatal enteritis. Following diagnosis, herds were treated with Trimethoprim + Sulfodoxine and multivitamin complexes. Intravenous and intramuscular administrations of these drugs were effective for both treatment and prevention of neonatal diarrhoea in lambs and kids.     

Prophylactic use of decoquinate for infections with Cryptosporidium parvum in experimentally challenged neonatal calves

OBJECTIVE: To evaluate the effect of daily oral administration of decoquinate to neonatal calves experimentally challenged with various numbers of Cryptosporidium parvum oocysts. DESIGN: Clinical trial. ANIMALS: 75 calves. PROCEDURE: Calves were purchased from a commercial dairy during a 5-week period. Calves were housed in individual hutches and fed milk replacer with or without decoquinate (2 mg/kg [0.9 mg/lb per day]). Calves were randomly assigned to treatment and 1 of 5 challenge groups (0, 50, 100, 1000, or 10,000 C. parvum oocysts in 60 mL of saline [0.9% NaCl] solution administered p.o. on the day after arrival). Calves were maintained in the study for as long as 28 days. Calves were clinically assessed for diarrhea and dehydration. Fecal samples were submitted for oocyst enumeration 3 times each week. RESULTS: Treatment did not affect number of days to first watery feces (diarrhea), number of days to first oocyst shedding, or duration of diarrhea or oocyst shedding. Duration of oocyst shedding was significantly associated with challenge dose of oocysts administered to calves and number of days to first oocyst shedding. Duration of diarrhea and number of days to first oocyst shedding were significantly associated with week of arrival and number of days to first watery diarrhea. CONCLUSIONS AND CLINICAL RELEVANCE: Daily treatment with decoquinate at the dosage used in this study did not affect oocyst shedding or clinical signs associated with cryptosporidiosis. However, there was an indication that if the number of oocysts calves received could be reduced, then the duration of oocyst shedding and, hence, environmental loading of C. parvum oocysts could be reduced.     

Field trial on the therapeutic efficacy of paromomycin on natural Cryptosporidium parvum infections in lambs

The objective of this study was to evaluate the therapeutic efficacy of paromomycin against cryptosporidiosis in naturally infected lambs under field conditions. The 36 cross-bred neonatal lambs, 3-10 days old, were used. On the first day that lambs showed diarrhea (Day 1) they were randomly divided into three groups. The infected control group (14 lambs) remained unmedicated whereas the two other groups were orally medicated with paromomycin solution (Humatin((R)), Parke Davis, France): 12 lambs (Group A) at 100mg/kg per day for three consecutive days (Days 1-3) and 10 lambs (Group B) at 200mg/kg per day for two days (Days 1 and 2). Drug efficacy was assessed by evaluating the presence of diarrhea, oocyst shedding and weight gains from Days 1 to 23. The results show the efficacy of paromomycin in reducing both cryptosporidial oocyst output and severity of clinical signs. On Day 4, all unmedicated lambs remained infected and excreted large numbers of cryptosporidial oocysts (mean score: 2.5) whereas oocyst output had stopped in most medicated lambs (>60%) and low numbers of oocysts were excreted in the remaining lambs (mean score: 0.45 in Group A and 1 in Group B). Mean oocyst excretion was significantly reduced in medicated lambs from Days 2 to 5 (P<0.05). Treatment also reduced, but not completely prevented, clinical symptoms although diarrhea stopped in most medicated lambs just after drug withdrawal. The mean weight gains of Group A lambs were higher than that of unmedicated lambs throughout the study and statistically significant differences were found from Days 1 to 11 (1.99+/-0.81 versus 1.47+/-0.53) (P<0.05). By contrast, the growth rate of Group B lambs from Days 11 to 23 was impaired when compared with the two other groups (P<0.05) although no significant differences were found at the end of the study (Days 1-23).     

Effects of leucocyte extract, levamisole and sulphadimidine on natural coccidial infections (Eimeria spp.) in young lambs

The efficacy of leucocyte extract (LE) and sulphadimidine in preventing coccidiosis in naturally infected lambs on pasture was evaluated in 3 separate experiments, whereas the prophylactic effect of levamisole was studied in 1 of the experiments. LE prepared from ewes immune to coccidia (Eimeria spp.) was administered either intravenously or intraperitoneally to young lambs 7, 5, or 2 days before they were turned out on pastures contaminated with coccidia. In all experiments, LE failed to transfer protective immunity to the lambs against the first coccidial infection on pasture. The LE preparations used apparently had an immunosuppressive effect, which resulted in more severe clinical signs of coccidiosis in the recipients. The lambs given LE showed a higher incidence of diarrhoea, a poorer weight gain, a higher mortality, and a higher oocyst output than the untreated control lambs. In lambs treated with sulphadimidine at 200 mg/kg on days 12, 13, and 14 after turnout there was a reduced severity of the coccidial infections in all experiments. The sulphadimidine-treated lambs had better weight gains and passed fewer oocysts than the controls during the third and fourth week after turnout, but some of them developed diarrhoea. Lambs treated with levamisole at 2 mg/kg 2 days before turnout, at turnout, and 2 days after turnout were more severely affected by the first coccidial infection on pasture than the controls.To study the lambs’ immunity against a heavy challenge infection with coccidia as compared with their immunity against the natural reinfection on pasture, some of the lambs from the original groups (untreated, sulphadimidine-treated, LE-treated) were each inoculated with 2 mill. Eimeria spp. oocysts about 6 weeks after turnout. The oocyst counts of the challenged lambs, except the LE-treated lambs, increased to a new peak 19–20 days after challenge. The challenge infection caused a softening of the faeces and a marked depression in weight gain in all challenged groups of lambs, mainly between days 10 and 17 after challenge. The lambs were thus only partially immune to coccidia after the first coccidial infection on pasture. The lambs treated with either LE or sulphadimidine in connection with the first coccidial infection on pasture were not appreciably more susceptible to the challenge infection than the untreated lambs.     

Control of cryptosporidiosis in neonatal goat kids: efficacy of a product containing activated charcoal and wood vinegar liquid (Obionekk®) in field conditions

Many compounds have been screened for their potential anti-cryptosporidial activity in ruminants but none of them has been totally efficient in controlling the disease. A product containing activated charcoal and wood vinegar liquid demonstrated a good efficacy in controlling clinical signs and oocyst excretion in calves experimentally infected. This product (Obionekk(?), Obione, Charentay, France) was given to goat kids in field conditions. The product was administered in a preventive way at the dose rate of 3.75 g/day/kid of Obionekk(?) from the age of 3 days to the age of 17 days in suspension in milk replacer twice or three times a day. A significant reduction of oocyst excretion was observed when the product was given 3 times a day when compared to control group. The clinical signs (diarrhoea) were significantly reduced whatever the rhythm of distribution when compared to control group. These results demonstrated the efficacy of Obionekk(?) in preventing cryptosporidiosis in goat kids in field conditions.     

Infectivity of Cryptosporidium sp isolated from wild mice for calves and mice

A study was conducted to determine the incidence of cryptosporidiosis in wild mice (Mus musculus) and the infectivity of oocysts from their feces for susceptible calves. The presence of oocysts and the duration of shedding of oocysts in the feces were evaluated in 115 wild mice. Approximately 30% of the mice shed Cryptosporidium sp oocysts, without evidence of clinical infection; recurrence of oocyst shedding was found in about 50% of the mice. Oocysts from the feces of naturally infected mice were infective for calves and mice. Calves began shedding oocysts at 7 days and shed oocysts for about 10 days. Nonfatal, clinical cryptosporidiosis developed in 7 infected calves. The mice began shedding oocysts at 6 days and shed oocysts for 12 days. Fatalities or clinical infection did not develop in 5 infected mice. The results indicated that Cryptosporidium-infected wild mice may be a source of cryptosporidiosis in susceptible calves.     

Pathogenicity of Cryptosporidium parvum--evaluation of an animal infection model

With the intention of developing a standardised method for assessment of pathogenicity of Cryptosporidium parvum, the CPB-0 isolate was studied by propagation in 1-day-old calves followed by inoculation into specific pathogen free (SPF) piglets. The experiment was repeated. Diarrhoea and shedding of oocysts were seen in all animals infected with the CPB-0 isolate. Clinical signs included depression, inappetence, vomiting (exclusively in the piglets), and death. Histological examination at 17 and 19 days post-infection revealed parasitic stages and microscopic changes primarily restricted to colon and rectum.The unintended presence of rotavirus in some of the experimental animals revealed an additive or synergistic effect between rotavirus and C. parvum as indicated by prolonged diarrhoea, increased oocyst shedding, decreased weight gain and elevated levels of serum haptoglobin and serum amyloid A (SAA) in piglets infected simultaneously with both pathogens. The difference in daily weight gain between infected and control animals was significant only for piglets co-infected with rotavirus. The acute phase response of haptoglobin and SAA was characterised by a large individual variation. In piglets, co-infected with rotavirus, the levels of serum haptoglobin were 3.5 and 4.6 times higher in the infected versus the controls 6 and 9dpi, respectively (mean values: 2411microg/ml+/-S.D. 2023 and 1840 microg/ml+/-S.D. 1697). In the controls infected with rotavirus, peak haptoglobin concentration was seen 3dpi (mean: 1022 microg/ml+/-S.D. 425). Elevated levels of SAA were seen in 1 of 6 piglets infected with C. parvum, and in 5 of 6 piglets co-infected with rotavirus. Tumour necrosis factor alpha (TNFalpha) was undetectable in all serum samples from piglets.The obvious advantages of the SPF pig model are the naturally acquired intestinal microflora, the development of distinct clinical signs similar to cryptosporidiosis in humans and calves, the size of the animals, and the accessibility of individuals born within a short time span. This makes the model ideal for dose-response studies, evaluation of therapeutic agents as well as for assessment of differences in the clinical response to isolates of diverse genetic background. In conclusion, it was shown that the CPB-0 isolate was pathogenic to calves and piglets at a dose of 2.5 x 10(5) oocysts, and that the clinical signs could be replicated during separate experiments. Moreover, diarrhoea, oocyst shedding, body weight changes, histological alterations, and the acute phase response of haptoglobin and SAA were identified as useful parameters for discrimination of isolate-specific differences of pathogenicity.     

Efficacy of alpha-cyclodextrin against experimental cryptosporidiosis in neonatal goats

The efficacy of orally administered tablets containing alpha-cyclodextrin, an excipient used in the pharmaceutical industry with demonstrated anticryptosporidial activity in vitro and in neonatal mice, was evaluated in neonatal goat kids. The formulation was evaluated for hardness and was subjected to in vitro drug release studies. Twenty goat kids were orally inoculated with 10(6) oocysts of C. parvum within the first 6 days of age. Half of the animals were treated by oral administration of four tablets of alpha-cyclodextrin/day (500 mg/kg of body weight) for six consecutive days, the treatment beginning on the day of inoculation. Infection was monitored by daily examination of faecal samples from the first day to 25 days post-inoculation. The criteria studied in evaluating efficacy were: oocyst shedding, presence of diarrhoea and weight gain at 15 and 25 days post-inoculation. alpha-cyclodextrin was effective when given at the beginning of infection: there was a longer pre-patent period, a reduction in the patent period and a decrease in the intensity of infection, these differences being statistically significant (P < 0.05) compared with untreated neonatal kids. Moreover, except in one animal, the diarrhoea was prevented in infected neonatal kids. Animals from both groups increased the body weight and no significant differences were seen between the two groups.     

Field study of the efficacy of halofuginone and decoquinate in the treatment of cryptosporidiosis in veal calves

Ninety, seven- to 10-day-old calves were allocated to three groups of 30 and treated daily for seven days with either 100 microg/kg halofuginone hydrobromide or 2.5 mg/kg decoquinate orally or left untreated as controls. The levels of diarrhoea and dehydration were monitored daily for 28 days from the first day of treatment (day 0) and samples of faeces were collected on days 0, 7, 14, 21 and 28, to quantify the excretion of Cryptosporidium parvum oocysts. The calves were weighed on days 3 and 28. The treatments had no effect on the levels of diarrhoea or dehydration, the proportions of diarrhoeic calves or the proportions of calves shedding oocysts. However, unlike decoquinate, halofuginone significantly reduced the excretion of oocysts on day 7 (P<0.0001), and decoquinate increased the average daily weight gain of the calves (P=0.049).