piperidines and Cryptosporidiosis

A prior systematic review on the efficacy of halofuginone (HFG) treatment to prevent or treat cryptosporidiosis in bovine calves was inconclusive. We undertook an updated synthesis and meta-analyses on key outcomes for the treatment of calves with HFG. Evaluated outcomes were oocyst shedding, diarrhoea, mortality and weight gain. Experiments had to describe results for same age animals in contemporary arms. Most doses were 100-150 mcg kg-1 day-1. Results were subgrouped by study design, experiments with the lowest risk of bias and lack of industry funding. Eighteen articles were found that described 25 experiments. Most evidence came from randomized controlled trials in Europe. Significantly lower incidence of oocyst shedding, diarrhoea burden and mortality was reported when treatment started before calves were 5 days old. Most studies reported on outcomes for animals up to at least 28 days old. Publication bias was possible in all outcomes and seemed especially likely for diarrhoea outcomes. Beneficial results when HFG treatment was initiated in calves older than 5 days were also found. Prophylactic treatment to prevent cryptosporidiosis is effective in preventing multiple negative outcomes and is beneficial to calf health and will result in a reduction of environmental contamination by Cryptosporidium oocysts.

Topics: Animals; Cattle; Cattle Diseases; Coccidiostats; Cryptosporidiosis; Cryptosporidium parvum; Diarrhea; Feces; Oocysts; Piperidines; Quinazolinones; Weight Gain

This is a review of the development of bumped-kinase inhibitors (BKIs) for the therapy of One Health parasitic apicomplexan diseases. Many apicomplexan infections are shared between humans and livestock, such as cryptosporidiosis and toxoplasmosis, as well as livestock only diseases such as neosporosis. We have demonstrated proof-of-concept for BKI therapy in livestock models of cryptosporidiosis (newborn calves infected with Cryptosporidium parvum), toxoplasmosis (pregnant sheep infected with Toxoplasma gondii), and neosporosis (pregnant sheep infected with Neospora caninum). We discuss the potential uses of BKIs for the treatment of diseases caused by apicomplexan parasites in animals and humans, and the improvements that need to be made to further develop BKIs.

Topics: Animals; Antiparasitic Agents; Apicomplexa; Cryptosporidiosis; Humans; One Health; Piperidines; Pyrimidines; Quinolines

Halofuginone seems to reduce diarrhoea and oocyst shedding in calves with cryptosporidiosis, but provides no complete cure. To develop more precise estimates of the effects of halofuginone on calf cryptosporidiosis, meta-analyses were performed, including studies on prophylactic and therapeutic treatment. Meta-analysis increases statistical power because several trials are evaluated together, increasing the effective sample size and possibility of detecting true effects. In total, 20 cohort or clinical studies (in 16 publications) investigating halofuginone treatment in calves were identified. One study was excluded because treated calves and control calves were not investigated in parallel. Four studies (three publications) were excluded because only abstracts were available. Thus, 15 studies from 12 publications, with 10-311 calves were included for data extraction. Of these, five studies from three publications could not be used for meta-analysis because they did not report the data needed. Effects on infection prevalence, diarrhoeal prevalence and mortality were investigated. For prophylactic treatment, halofuginone had an effect on infection and diarrhoeal prevalence on study days 4 and 7, but the control group had significantly lower infection prevalence than the halofuginone treated group on study day 21. Heterogeneity was detected on study days 14 and 21 and publication bias was detected on study days 7 and 14. Mortality was not affected. For therapeutic treatment, a shortage of studies in combination with heterogeneity made interpretations uncertain, and we could not determine if halofuginone treatment benefits calves.

Topics: Animals; Cattle; Cattle Diseases; Clinical Trials as Topic; Coccidiostats; Cryptosporidiosis; Mass Screening; Meta-Analysis as Topic; Piperidines; Prevalence; Quinazolinones; Sweden

Halofuginone lactate (HL) is registered in several countries for the prevention of calf cryptosporidiosis, but the compound's utility in the presence of co-infection with other enteropathogens is not well understood. We performed a randomized controlled field trial of the efficacy of HL for the prevention of natural calf cryptosporidiosis, in the presence of co-infection with rotavirus and Salmonella Typhimurium. Newborn calves on one farm were sequentially enrolled and allocated to a full dose (n=15), half dose (n=15), or a placebo control group (n=15), using a randomized block design. The Cryptosporidium oocysts in fecal specimens collected on Days 6, 8, 10, 14 and 20 were counted and the severity of the diarrhea was assessed using fecal consistency scores (solid, semisolid, or liquid). The oocyst numbers and fecal consistency scores were statistically compared between the groups. Ninety one percent of the calves shed Cryptosporidium parvum oocysts during the trial. The full dose group had a longer prepatent period than the control group, but no statistical difference in the number of oocysts was identified between the groups after controlling for the effects of sex and breed. The fecal consistency scores and mortality rates did not differ between the groups. These results indicated that the anti-Cryptosporidium activity and clinical benefit of HL were limited. It is concluded that in order to maximize the clinical efficacy of HL in the field, diagnostic efforts should aim to rule out the presence of other enteropathogens.

Topics: Animals; Cattle; Cattle Diseases; Cryptosporidiosis; Feces; Female; Male; Oocysts; Piperidines; Quinazolinones; Rotavirus; Rotavirus Infections; Salmonella Infections, Animal; Salmonella typhimurium

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.

Topics: Animals; Anti-Infective Agents; Cattle; Cattle Diseases; Coccidiostats; Cryptosporidiosis; Cryptosporidium; Dairying; Diarrhea; Feces; Female; Germany; Oocysts; Piperidines; Prevalence; Quinazolines; Quinazolinones; Sulfamethazine; Surveys and Questionnaires

Velez J, Lange MK, Zieger P et al. Long-term use of yeast fermentation products in comparison to halofuginone for the control of cryptosporidiosis in neonatal calves. Vet Parasitol 2019; 269: 57–64 KRYPTOSPORIDIEN SIND WELTWEIT VORKOMMENDE PATHOGENE PROTOZOEN VON WIRBELTIEREN. CRYPTOSPORIDIUM PARVUM ZäHLT ZU DEN WICHTIGSTEN DURCHFALLERREGERN BEIM NEONATALEN KALB. NACH ORALER AUFNAHME KOMMT ES HäUFIG ZU EINER STARKEN VERMEHRUNG IM MIKROVILLISAUM DES DARMEPITHELS GEFOLGT VON MALABSORPTION MIT AKUTER WäSSRIGER DIARRHö, SCHWäCHE UND ABMAGERUNG BEI Z. T. STARK GESTöRTEM ALLGEMEINBEFINDEN. DER HOCHGRADIGEN FäKALEN AUSSCHEIDUNG VON OOZYSTEN FOLGT EINE MONATELANGE PERSISTENZ DIESER INFEKTIöSEN STADIEN. DIE INFEKTION IST NACH MEHREREN TAGEN SELBSTLIMITIEREND.: ZUR BEHANDLUNG STEHEN 2 WIRKSTOFFE MIT ANTIKRYPTOSPORIDIALER WIRKUNG ZUR VERFüGUNG, HALOFUGINON UND PAROMOMYCIN, WOBEI NUR HALOFUGINON EINE ZULASSUNG ZUR KRYPTOSPORIDIOSETHERAPIE HAT. NEBEN EINER ENGEN THERAPEUTISCHEN BREITE BEWIRKT HALOFUGINON BEI AKUTER ERKRANKUNG KEINE VERBESSERUNG DES KLINISCHEN ZUSTANDS. AKTUELLEN STUDIEN ZUFOLGE REDUZIERTE DIE 4-WöCHIGE VERFüTTERUNG VON FERMENTATIONSPRODUKTEN DER HEFE SACCHAROMYCES CEREVISIAE AN NEUGEBORENE, KRYPTOSPORIDIUMINFIZIERTE KäLBER DIE SCHäDIGUNG DER DüNNDARMZOTTEN IM VERGLEICH ZU KONTROLLTIEREN. DIES DEUTET AUF EINE PROPHYLAKTISCHE WIRKSAMKEIT GEGENüBER DER INFEKTION HIN. ZIEL DER STUDIE WAR, DIE WIRKUNG VON GVO-FREIEN SACCHAROMYCES CEREVISIAE-FERMENTATIONSPRODUKTEN MIT DER EINER HALOFUGINON-BEHANDLUNG GEGEN EINE CRYPTOSPORIDIUM PARVUM-INFEKTION BEI KäLBERN IN EINEM MILCHVIEHBETRIEB ZU VERGLEICHEN.

Topics: Animals; Cattle; Cryptosporidiosis; Fermentation; Piperidines; Quinazolinones

Recent studies have illustrated the burden Cryptosporidium infection places on the lives of malnourished children and immunocompromised individuals. Treatment options remain limited, and efforts to develop a new therapeutic are currently underway. However, there are unresolved questions about the ideal pharmacokinetic characteristics of new anti-Cryptosporidium therapeutics. Specifically, should drug developers optimize therapeutics and formulations to increase drug exposure in the gastrointestinal lumen, enterocytes, or systemic circulation? Furthermore, how should researchers interpret data suggesting their therapeutic is a drug efflux transporter substrate? In vivo drug transporter-mediated alterations in efficacy are well recognized in multiple disease areas, but the impact of intestinal transporters on therapeutic efficacy against enteric diseases has not been established. Using multiple in vitro models and a mouse model of Cryptosporidium infection, we characterized the effect of P-glycoprotein efflux on bumped kinase inhibitor pharmacokinetics and efficacy. Our results demonstrated P-glycoprotein decreases bumped kinase inhibitor enterocyte exposure, resulting in reduced in vivo efficacy against Cryptosporidium. Furthermore, a hollow fiber model of Cryptosporidium infection replicated the in vivo impact of P-glycoprotein on anti-Cryptosporidium efficacy. In conclusion, when optimizing drug candidates targeting the gastrointestinal epithelium or gastrointestinal epithelial infections, drug developers should consider the adverse impact of active efflux transporters on efficacy.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biological Transport, Active; Caco-2 Cells; Cell Membrane Permeability; Cryptosporidiosis; Cryptosporidium; Disease Models, Animal; Drug Discovery; Enterocytes; Female; Gastrointestinal Absorption; Humans; Interferon-gamma; Intestinal Diseases, Parasitic; Mice; Mice, Knockout; Naphthalenes; Piperidines; Pyrazoles; Pyrimidines; Quinolines; Treatment Outcome

There are no standard guidelines for the treatment of cryptosporidiosis in reptiles. The aim of this study was to evaluate the efficacy of two cryptosporidiosis therapies in captive green iguanas. Eight green iguanas aged 2-6 years, including 6 (1 ♂ and 5 ♀) animals with chronic diarrhea, received treatment for cryptosporidiosis. The presence of Cryptosporidium sp. oocysts was determined in 8 iguanas (100%), Isospora sp. oocysts were detected in 3 animals (37.5%), and Oxyuridae eggs were observed in 5 iguanas (62.5%). The animals were divided into two therapeutic groups (A and B). Group A iguanas were administered halofuginone (Halocur, 0,50 mg/ml Intervet Productions S.A., France) at a dose of 110 mg/kg body weight (BW) every 7 days for 5 weeks. Group B animals were administered sulfadiazine and trimethoprim (Norodine Vet Oral Paste sulfadiazine 288,3 mg/g, trimethoprim 58 mg/g, ScanVet Animal Health A/S, Denmark) at 75 mg/kg BW per os every 5 days for 5 weeks and spiramycin and metronidazole (Stomorgyl, spiramycin 1500000 IU, metronidazole 250 mg, Merial, France) at 200 mg/kg BW every 5 days for 5 weeks. Both groups received hyperimmune bovine colostrum and subcutaneous fluids. Before treatment, the average number of Cryptosporidium sp. oocysts in 1 g of feces was determined at 1.71 * 10

Topics: Animals; Coccidiostats; Cryptosporidiosis; Cryptosporidium; Feces; Iguanas; Intestinal Mucosa; Oocysts; Piperidines; Poland; Quinazolinones; Sulfadiazine; Treatment Outcome; Trimethoprim

Topics: Animals; Animals, Newborn; Cattle; Cattle Diseases; Coccidiostats; Cryptosporidiosis; Germany; Piperidines; Quinazolinones

Recent reports highlighting the global significance of cryptosporidiosis among children have renewed efforts to develop control measures. We evaluated the efficacy of bumped kinase inhibitor (BKI) 1369 in the gnotobiotic piglet model of acute diarrhea caused by

Topics: Acute Disease; Animals; Animals, Newborn; Antiprotozoal Agents; Cryptosporidiosis; Cryptosporidium; Diarrhea; Disease Models, Animal; Germ-Free Life; Oocysts; Parasite Load; Piperidines; Pyrimidines; Quinolines; Swine

There is a substantial need for novel therapeutics to combat the widespread impact caused by Crytosporidium infection. However, there is a lack of knowledge as to which drug pharmacokinetic (PK) characteristics are key to generate an in vivo response, specifically whether systemic drug exposure is crucial for in vivo efficacy. To identify which PK properties are correlated with in vivo efficacy, we generated physiologically based PK models to simulate systemic and gastrointestinal drug concentrations for a series of bumped kinase inhibitors (BKIs) that have nearly identical in vitro potency against Cryptosporidium but display divergent PK properties. When BKI concentrations were used to predict in vivo efficacy with a neonatal model of Cryptosporidium infection, these concentrations in the large intestine were the sole predictors of the observed in vivo efficacy. The significance of large intestinal BKI exposure for predicting in vivo efficacy was further supported with an adult mouse model of Cryptosporidium infection. This study suggests that drug exposure in the large intestine is essential for generating a superior in vivo response, and that physiologically based PK models can assist in the prioritization of leading preclinical drug candidates for in vivo testing.

Topics: Animals; Cryptosporidiosis; Cryptosporidium parvum; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Gastrointestinal Tract; Inhibitory Concentration 50; Mice; Mice, Knockout; Models, Theoretical; Naphthalenes; Piperidines; Protein Kinase Inhibitors; Pyrazoles

The aim of this study was to determine whether there is an association between Cryptosporidium infections in calves and immunological factors, as well as farm-related factors or the application of the anti-cryptosporidiosis drug Halofuginone. From January to June 2010, 63 cow-calf-pairs from 20 different farms near Zürich, Switzerland have been investigated. Each cowcalf- pair was visited three times within the first 6 weeks of life to collect data of the farm and animals, as well as blood, faecal, colostral and milk samples. An ELISA using sporozoite antigen was developed for the specific detection of anti-Cryptosporidium-IgG in blood- and colostral serum. The IgG concentration in the bloodand colostral serum was determined using radial immuno diffusion test (RID). White blood cell isolation and differential blood cell counts and California Mastitis Test were performed. Bacteriological studies on quarter-milk-samples were carried out. Cryptosporidium oocysts were diagnosed with the modified Ziehl-Neelsen staining, other protozoa with the SAFC method and Eimeria oocysts and helminth eggs were diagnosed with the combined sedimentation/floatation test. ELISAs were performed for the detection of rota- and coronavirus, E. coli F5 and Cryptosporidium spp. in bovine feces (bio-X Diagnostics®, Belgium). The highest prevalence of Cryptosporidium oocysts was 54.0% and found 7 to 20 days post natum, whereas 47.1% were suffering from diarrhea. The transfer of total IgG with the colostrum and the humoral immunity of the calf could not prevent any infection with Cryptosporidium, but the severity of the diarrhea symptoms decreased with increasing total IgG concentrations. Calves housed in open sheds showed significantly more often diarrhea, i. e. they shed more Cryptosporidium oocysts during the first 4 days and 7 to 20 days post natum, respectively. Halofuginone (Halocur®) is approved for prophylaxis against cryptosporidiosis, but it showed no effect on the excretion of Cryptosporidium oocysts in the present study.. Ziel dieser Studie war es, einen Zusammenhang zwischen dem Vorkommen von Cryptosporidien und immunologischen Faktoren, sowie Betriebsfaktoren und die Verwendung von Halofuginon, zu untersuchen. Von Januar bis Juni 2010 wurden im Kanton Zürich 63 Mutter- Kalb-Paare aus 20 verschiedenen Betrieben untersucht. Innerhalb von 6 Wochen erfolgten zu ausgewählten Zeitpunkten drei Besuche. Dabei wurden Bestandsdaten erhoben, wie auch Blut-, Kot-, Kolostrum-, respektive Milchproben untersucht. Zum Nachweis von anti-Cryptosporidien-IgG im Blut- und Kolostrum- Serum wurde ein ELISA mit Sporozoiten-Antigen entwickelt. Die IgG-Konzentration im Kolostrum- und Blutserum wurde mittels RID (Radialer Immundiffusionstest) bestimmt. Zusätzlich wurde bei der Kuh und beim Kalb ein Differenzialblutbild erstellt und beim Muttertier ein Schalmtest durchgeführt. Bakteriologische Untersuchungen erfolgten an Vierviertelgemelksproben. Cryptosporidien-Oozysten wurden durch eine modifizierte Ziehl-Neelsen-Färbung, andere Protozoen durch die SAFC-Methode nachgewiesen und mittels kombiniertem Sedimentations-/Flotationsverfahren wurden Helminthen-Eier und Eimeria-Oozysten erfasst. Ein ELISA diente dem Nachweis von Rota- und Coronaviren, E. coli F5 und Cryptosporidium spp. in bovinem Faeces (Bio-X Diagnostics®, Belgien). Die Prävalenz von Cryptosporidien-Infektionen war zwischen dem 7. und 20. Lebenstag der Kälber am höchsten (54.0%), wobei 47.1% dieser Kälber an Durchfall litten. Offenställe steigerten signifikant das Risiko für Durchfall, bzw. für Cryptosporidien-Ausscheidung zwischen dem 1. und 4., bzw. zwischen dem 7. und 20. Lebenstag. Die Übertragung von Total-IgG mit dem Kolostrum und die humorale Immunität des Kalbes konnten keine Infektion mit Cryptosporidien verhindern, der Schweregrad der Durchfallsymptomatik nahm aber mit zunehmender total IgG-Konzentration ab. Der für die Prophylaxe gegen Cryptosporidiose zugelassene Wirkstoff Halofuginon zeigte in dieser Studie keine Wirkung auf die Ausscheidung von Cryptosporidien-Oocysten.. Le but de la présente étude était d’étudier s’il existe un rapport entre l’apparition de cryptosporidies et des facteurs immunologiques, des facteurs liés à l’exploitation ainsi qu’à l’usage d’halofuginone. De janvier à juin 2010, on a examiné 63 paires mère-veau provenant de 20 exploitations du canton de Zürich. Au cours de 6 semaines on a effectué, à des moments choisis, trois visites. A ces occasions, des données relatives à l’exploitation ainsi que des échantillons de sang, de selles, de colostrum respectivement de lait ont été collectés. On a développé un test ELISA avec des antigènes de sporozoïtes pour mettre en évidence la présence IgG anti-cryptosporidies dans le sang et dans le colostrum. La concentration en IgG dans le colostrum et dans le sérum a été mesurée avec un test d’immunodiffusion radiale (RID). En outre on a réalisé une image sanguine différentielle des vaches et des veaux et effectué un test de Schalm chez les vaches. Un examen bactériologique a été réalisé sur un échantillon provenant des quatre quartiers. Les oocystes de cryptosporidies ont été mis en évidence au moyen d’une coloration de Ziehlk-Neelsen modifiée, les autres protozoaires ont été mis en évidence par la méthode SAFC et les oeufs d’helminthes ainsi que les oocystes d’Eimeria par un processus de sédimentation-flottation combiné. Un test ELISA a été utilisé pour les rota- et les coronavirus, les E. coli F5 et Cryptosporidium spp. dans les selles des bovins (Bio-X Diagnostics®, Belgique). La prévalence d’infections par des cryptosporidies était maximale entre le 7ème et le 20ème jour de vie des veaux (50.4%), 47.1% de ces veaux souffrant de diarrhée. Les stabulations libres augmentaient de façon significative le risque de diarrhée et d’excrétion de cryptosporidies entre le 1er et le 4ème jour respectivement entre le 7ème et le 20ème jour. La transmission d’IgG et l’immunité humorale des veaux n’empêchaient pas l’infection par des cryptosporidies mais la gravité de la diarrhée diminuait avec l’augmentation de la concentration des IgG totales. L’halofuginone, substance enregistrée pour la prophylaxie de la cryptosporidiose, n’a pas montré, dans cette étude, d’efficacité pour empêcher l’excrétion d’oocystes de cryptosporidies.. Lo scopo di questo studio è di indagare sulla correlazione tra la presenza di Cryptosporidium e fattori immunologici e aziendali nonché l’uso di alofuginone. Da gennaio a giugno 2010, nel Canton Zurigo sono state esaminate 63 coppie madre-vitello provenienti da 20 diverse aziende. Nello spazio di 6 settimane sono state eseguite, in momenti determinati, tre visite che hanno raccolto dati sulla mandria e esaminati campioni di sangue, escrementi, colostro e latte. Per rilevare la presenza di anti-IgG Cryptosporidium nel sangue e nel siero di colostro è stato sviluppato un test ELISA con un antigene sporozoite. La concentrazione di IgG nel siero di colostro e nel siero sanguigno è stata determinata mediante RID (test di immunodiffusione radiale). Inoltre, è stato eseguito sulla bovina e sul vitello un emocromo differenziale e sulla vacca madre un CMT. Esami batteriologici sono stati eseguiti su campioni di latte proveniente dai quattro quarti. Oocisti di Cryptosporidium sono stati rilevati da una colorazione di Ziehl-Neelsen, gli altri protozoi con il metodo SAFC mentre con una combinazione di processi di sedimentazione/flottazione sono state rilevate uova di elminti e oocisti di Eimeria. Un test ELISA è stato utilizzato per provare la presenza di Rotavirus e Coronavirus, E. Coli F5 e Cryptosporidium spp nelle feci bovine (Bio-X Diagnostics®, Belgio). La prevalenza di infezioni da Cryptosporidium si situava tra il 7° e il 20° giorno di vita del vitello ad alto livello (54.0%); il 47.1% di questi vitelli soffriva di diarrea. Il rischio di diarrea aumentava significativamente in caso di stalle aperte rispettivamente le secrezioni di Cryptosporidium tra il 1° e il 4° risp. il 7° e il 20° giorno di vita. La trasmissione con il colostro di IgG totali e l’immunità umorale dei vitelli non hanno potuto prevenire l’infezione da Cryptosporidium ma la gravità dei sintomi della diarrea diminuiva con l’aumento della concentrazione di IgG totali. In questo studio, l’approvato principio attivo alofuginone per la profilassi contro la cryptosporidiosi non ha mostrato nessun effetto sulla secrezione di oocisti di Cryptosporidium.

Topics: Animals; Cattle; Cattle Diseases; Coccidiostats; Cryptosporidiosis; Enzyme-Linked Immunosorbent Assay; Housing, Animal; Immunoglobulin G; Piperidines; Prevalence; Quinazolinones; Risk Factors; Switzerland; Time Factors

We describe an outbreak of cryptosporidiosis in Stone curlews kept in a mixed-species rearing unit in Dubai. Cryptosporidium was the predominant intestinal pathogen detected, although microbiological investigations revealed a concurrent Salmonella infantis infection in two of the 29 Stone curlew chicks that died. Nineteen of 29 birds had catarrhal enteritis associated with histopathological findings of numerous Cryptosporidium developmental stages at the mucosal surface. Catarrhal enteritis was present without associated Cryptosporidium oocysts in five cases. Histology of the intestine, faecal examination by direct microscopy and antigenic detection by immunochromatography revealed the presence of Cryptosporidium spp. associated with catarrhal enteritis in intestinal sections and faeces. Clinical and histopathological outcomes of infection were severe, including disruption of intestinal epithelial integrity, the presence of numerous endogenous Cryptosporidium stages in intestinal epithelia and the excretion of large numbers of sporulated oocysts. The application of polymerase chain reaction and restriction fragment length polymorphism techniques at two 18S rRNA and one Cryptosporidium oocyst wall protein gene locus confirmed the presence of Cryptosporidium parvum DNA in faecal samples.

Topics: Animals; Antiprotozoal Agents; Bird Diseases; Birds; Cryptosporidiosis; Disease Outbreaks; Feces; Piperidines; Quinazolinones; Spiramycin; Triazines; United Arab Emirates

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).

Topics: Animals; Cattle; Cattle Diseases; Coccidiostats; Cryptosporidiosis; Cryptosporidium parvum; Decoquinate; Dehydration; Diarrhea; Feces; Female; Male; Parasite Egg Count; Piperidines; Quinazolinones; Random Allocation; Treatment Outcome; Weight Gain

Inflammatory bowel disease (IBD) is a chronic, debilitating disorder of uncertain and perhaps multiple etiologies. It is believed to be due in part to disregulation of the immune system. Neuroimmune interactions may be involved in induction or maintenance of IBD. In the present study, we examined the potential role of a neurotransmitter, substance P, in a mouse model of IBD. We found that binding sites for substance P, and more specifically, neurokinin-1 receptors, were upregulated in intestinal tissue of mice with IBD-like syndrome. Dosing of mice with LY303870, a neurokinin-1 receptor antagonist, reduced the severity of IBD, and treatment of mice with preexisting IBD allowed partial healing of lesions. We hypothesize that blocking the binding of substance P to the neurokinin-1 receptor interrupts the inflammatory cascade that triggers and maintains intestinal lesions of IBD.

Topics: Animals; Autoradiography; Cattle; Cryptosporidiosis; Cryptosporidium parvum; Disease Models, Animal; Gene Expression; Indoles; Inflammatory Bowel Diseases; Mice; Mice, Mutant Strains; Neurokinin-1 Receptor Antagonists; Piperidines; Receptors, Antigen, T-Cell, alpha-beta; Receptors, Neurokinin-1; RNA, Messenger

Halofuginone was evaluated for its activity against experimentally induced infection due to Cryptosporidium parvum in rats rendered immunosuppressed with dexamethasone. The drug's activity was dose-related and both prophylaxis and therapy reduced the rate and severity of infection in the small intestine and caecum. Prophylactic treatment reduced infection of the common bile duct, but therapeutic administration did not and neither form of treatment reduced the infection rate in the colon. Intestinal infection recurred at a level comparable to that of untreated controls when treatment was discontinued. Treatment with halofuginone may reduce the severity of acute cryptosporidiosis, but is less efficacious for chronic cryptosporidiosis involving the colon and extraintestinal tissues, a manifestation increasingly seen in the immunocompromised host.

Topics: Animals; Colonic Diseases; Common Bile Duct; Cryptosporidiosis; Cryptosporidium parvum; Dexamethasone; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Feces; Female; Immunosuppression Therapy; Intestine, Large; Intestine, Small; Parasite Egg Count; Piperidines; Quinazolines; Quinazolinones; Rats; Rats, Sprague-Dawley; Treatment Outcome

Chemoprophylaxis of Cryptosporidium baileyi infections was attempted by feeding 4 groups of chicks diets containing 3 mg of halofuginone/kg of feed, 60 mg of salinomycin/kg, 75 mg of lasalocid/kg, or 110 mg of monensin/kg. Rations were fed 5 days before oral or intratracheal inoculation with oocysts and were continued for 20 days. None of the drugs prevented C baileyi infections. Clinical signs of respiratory tract disease and gross lesions of airsacculitis were observed in intratracheally inoculated birds in all treatment groups and nonmedicated controls. Orally inoculated birds did not develop clinical signs of infection. Pathogenic bacteria were not isolated from the respiratory tract systems of any chicks. Halofuginone delayed the establishment of infections of the bursa of Fabricius and cloaca, but not of the trachea.

Topics: Animals; Chickens; Coccidiostats; Cryptosporidiosis; Lasalocid; Monensin; Piperidines; Poultry Diseases; Pyrans; Quinazolines; Quinazolinones