Piglet coccidiosis in Belgium and the Netherlands: Prevalence, management and potential risk factors.

Piglet coccidiosis caused by Cystoisospora suis is one of the most important causes of diarrhea in suckling piglets. The parasite has a fast development and multiplies quickly and effectively under the conditions of a farrowing unit. Control measures include cleaning and disinfection and anticoccidial treatment. In Europe, toltrazuril-based products are authorized for this purpose and are applied to piglets on affected farms in the first week of life. To observe the effect of treatment and disinfection on the control of piglet coccidiosis in the field, 23 farms (11 from Belgium, 12 from the Netherlands, mean number of sows = 1413) were sampled twice by litter in the second and third week of life and fecal scores and the presence of C. suis oocysts were determined. A questionnaire was used to collect data on farm sizes, management and hygiene measures as well as treatment (product, dose and piglet age). Thirteen farms regularly treated with toltrazuril (treatment age: 1-6 days, mean 4.3 days) and 19 applied disinfection. Parasite excretion was documented on 60.9% and diarrhea on 78.3% of farms and in 34.3%/15.7% of the litters. Only 2.4% of the litters showed both, so subclinical infection appeared to be common. No significant differences between farms that did not treat against coccidiosis and farms that applied toltrazuril was observed with regard to C. suis oocysts shedding and/or diarrhea. However, in litters that were treated within the first three days of life, oocyst excretion was significantly less often observed than in litters with later treatment (p = 0.033). No significant effect of disinfection could be shown, but most farms applied disinfectants that have no proven effect against coccidia (oxygen-releasing agents or glutaraldehyde + ammonia) while the only farm that used chlorocresols (which are effective against coccidia) did not show oocyst shedding. Current control measures thus appear to be insufficient on most of the examined farms. It is therefore recommended to treat piglets timely and to apply effective disinfectants to reduce C. suis infections. Furthermore, regular evaluation of sustained efficacy of all implemented measures are necessary.

Comparative assessment of the effects of bumped kinase inhibitors on early zebrafish embryo development and pregnancy in mice.

Bumped kinase inhibitors (BKIs) are effective against a variety of apicomplexan parasites. Fifteen BKIs with promising in vitro efficacy against Neospora caninum tachyzoites, low cytotoxicity in mammalian cells, and no toxic effects in non-pregnant BALB/c mice were assessed in pregnant mice. Drugs were emulsified in corn oil and were applied by gavage for 5 days. Five BKIs did not affect pregnancy, five BKIs exhibited ~15-35% neonatal mortality and five compounds caused strong effects (infertility, abortion, stillbirth and pup mortality). Additionally, the impact of these compounds on zebrafish (Danio rerio) embryo development was assessed by exposing freshly fertilised eggs to 0.2-50 µM of BKIs and microscopic monitoring of embryo development in a blinded manner for 4 days. We propose an algorithm that includes quantification of malformations and embryo deaths, and established a scoring system that allows the calculation of an impact score (Si) indicating at which concentrations BKIs visibly affect zebrafish embryo development. Comparison of the two models showed that for nine compounds no clear correlation between Si and pregnancy outcome was observed. However, the three BKIs affecting zebrafish embryos only at high concentrations (≥40 µM) did not impair mouse pregnancy at all, and the three compounds that inhibited zebrafish embryo development already at 0.2 µM showed detrimental effects in the pregnancy model. Thus, the zebrafish embryo development test has limited predictive value to foresee pregnancy outcome in BKI-treated mice. We conclude that maternal health-related factors such as cardiovascular, pharmacokinetic and/or bioavailability properties also contribute to BKI-pregnancy effects.

Efficacy and economic analysis of two treatment regimens using toltrazuril in lambs naturally infected with Eimeria spp. on pasture.

This study evaluated the efficacy and the economic viability of two anticoccidial treatment regimens tested in lambs naturally exposed to Eimeria spp. re-infections in a grazing system during a 140-day period. Twenty-four suckling lambs were distributed into three groups based on the individual count of oocysts per gram of feces (OPG) and body weight. Animals were treated with toltrazuril 5% (20 mg/kg) at 14- (GI) or 21-day (GII) intervals, and GIII was kept as untreated control. A cost-benefit analysis of each treatment regimen was calculated. Additionally, economic analysis was performed on four hypothetical scenarios, in which lambs could be having 10, 25, 50, or 85% decrease in their expected body weight gain due to clinical. Efficacy of toltrazuril against Eimeria spp. was 96.9-99.9% (GI) and 74.2-99.9% (GII). E. ovinoidalis was most frequently identified, but no clinical signs of coccidiosis were observed in lambs. There were no differences in weight gain among the groups. The cost of treatment per lamb was $13.09 (GI) and $7.83 (GII). The estimation model showed that the cost-benefit ratio favored treatment with toltrazuril when lambs fail to gain weight. In the studied flock, the break-even point for toltrazuril administered at 14-day intervals was reached with 85% decrease in mean weight gain. In conclusion, toltrazuril can be used at 14-day intervals to control Eimeria spp. (re)-infection in lambs raised on pasture. This treatment regimen was not economically feasible for subclinical coccidiosis; however, it may be feasible when used to prevent weight loss caused by clinical coccidiosis.

Assessment of probiotics supplementation via feed or water on the growth performance, intestinal morphology and microflora of chickens after experimental infection with Eimeria acervulina, Eimeria maxima and Eimeria tenella.

In this study, the effect of probiotic supplementation via drinking water or feed on the performance of broiler chickens experimentally infected with sporulated oocysts of Eimeria acervulina (5 × 10(4)), Eimeria maxima and Eimeria tenella (2 × 10(4) each one) at 14 days of age was evaluated. Two hundred and forty 1-day-old Ross 308 male chicks were separated into eight equal groups with three replicates. Two of the groups, one infected with mixed Eimeria oocysts and the other not, were given a basal diet and served as controls. The remaining groups were also challenged with mixed Eimeria species and received the basal diet and either water supplemented with probiotic (three groups) or probiotic via feed (two groups); the probiotic used consisted of Enterococcus faecium #589, Bifidobacterium animalis #503 and Lactobacillus salivarius #505 at a ratio of 6:3:1. Probiotic supplementation was applied either via drinking water in different inclusion rates (groups W1, W2 and W3) or via feed using uncoated (group FN) or coated strains (group FC). The last group was given the basal diet supplemented with the anticoccidial lasalocid at 75 mg/kg. Each experimental group was given the corresponding diet or drinking water from day 1 to day 42 of age. Throughout the experimental period of 42 days, body weight and feed intake were recorded weekly and feed conversion ratios were calculated. Seven days after infection, the infected control group presented the lowest weight gain values, while probiotics supplied via feed supported growth to a comparable level with that of the lasalocid group. Probiotic groups presented lesion score values and oocyst numbers that were lower than in control infected birds but higher than in the lasalocid group. In the duodenum, jejunum and ileum, the highest villous height values were presented by probiotic groups. In conclusion, a mixture of probiotic substances gave considerable improvement in both growth performance and intestinal health in comparison with infected control birds and fairly similar improvement to an approved anticoccidial during a mixed Eimeria infection.

Epidemiology and economic benefits of treating rabbits coccidiosis in small farms from West Pomerania province, Poland.

The studies were carried out on 9 farms which deals with meat race of rabbits breeding. The basic herds had from 28 to 63 rabbits (total 275 rabbits) on Choszczno and Recz district in West Pomerania province. The study was based on two flotation methods:Willis-Schlaaf for qualitative and McMaster for quantitative analysis, which helped to establish the number of oocysts in 1g of feces (OPG). Ten species of coccidian were found in which 9 were intestinal (E. exigua, E. perforans, E. media, E. magna, E. irresidua, E. coecicola, E. flavescens, E. piriformis, E. intestinalis) and one was living in liver (E. stiedai). Baycox (Bayer) was used in drinking water in a dose of 25 ppm in 1 liter of water for 2 days. In rabbits from the experimental groups higher weight gain and lower mortality compared to the control group animals were observed. The results highlight the beneficial effects of coccidiostats used in the production effects in rabbits.

Eimeria tenella glucose-6-phosphate isomerase: molecular characterization and assessment as a target for anti-coccidial control.

Limitations with current chemotherapeutic and vaccinal control of coccidiosis caused by Eimeria species continue to prompt development of novel controls, including the identification of new drug targets. Glucose-6-phosphate isomerase (G6-PI) has been proposed as a valid drug target for many protozoa, although polymorphism revealed by electrophoretic enzyme mobility has raised doubts for Eimeria. In this study we identified and sequenced the Eimeria tenella G6-PI orthologue (EtG6-PI) from the reference Houghton strain and confirmed its position within the prevailing taxonomic hierarchy, branching with the Apicomplexa and Plantae, distinct from the Animalia including the host, Gallus gallus. Comparison of the deduced 1647 bp EtG6-PI coding sequence with the 9016 bp genomic locus revealed 15 exons, all of which obey the intron-AG-/exon/-GT-intron splicing rule. Comparison with the Weybridge and Wisconsin strains revealed the presence of 33 single nucleotide polymorphisms (SNPs) and 14 insertion/deletion sites. Three SNPs were exonic and all yielded non-synonymous substitutions. Preliminary structural predictions suggest little association between the coding SNPs and key G6-PI catalytic residues or residues thought to be involved in the coordination of the G6-PI's substrate phosphate group. Thus, the significant polymorphism from its host orthologue and minimal intra-specific polymorphism suggest G6-PI remains a valid anti-coccidial drug target.

Simple stochastic fingerprints towards mathematical modelling in biology and medicine. 1. The treatment of coccidiosis.

We have developed a classification function that is capable of discriminating between anticoccidial and nonanticoccidial compounds with different structural patterns. For this purpose, we calculated the Markovian electron delocalization negentropies of several compounds. These molecular descriptors, which act as molecular fingerprints, are derived from an electronegativity-weighted stochastic matrix (1Pi). The method attempts to describe the delocalization of electrons with time during the process of molecule formation by considering the 3D environment of the atoms. Accordingly, the entropies of this random process are used as molecular descriptors. The present study involves a stochastic generalization of the original idea described by Kier, which concerned the use of molecular negentropies in QSAR. Linear discriminant analysis allowed us to fit the discriminant function. This function has given rise to a good classification of 82.35% (28 anticoccidials out of 34) and 91.8% of inactive compounds (56/61) in training series. An overall classification of 88.42% (84/95) was achieved. Validation of the model was carried out by means of an external predicting series and this gave a global predictability of 93.1%. Finally, we report the experimental assay (more than 95% of lesion control) of two compounds selected from a large data set through virtual screening. We conclude that the approach described here seems to be a promising 3D-QSAR tool based on the mathematical theory of stochastic processes.

Chemotherapeutic approaches to protozoa: Coccidiae--current level of knowledge and outlook.

Progress in the treatment and prophylaxis of cyst-forming coccidial infections (Neospora, Sarcocystis Toxoplasma) and Cryptosporidium infections has been limited (Table 1: Haberkorn 1996: Croft 1997: Wang 1997). However, new possibilities have been opened up in the treatment of Eimeria-induced coccidiosis in poultry and mammals. due to improvements in treatment and, or metaphylaxis. A new polyether antibiotic. semduramycin, has recently been added to the range of effective prophylactic preparations. The development of resistance to anticoccidial agents is now posing similar problems to those encountered with malaria, coccidiosis in poultry being particularly affected. Because no new active ingredient from a new family of chemical substances has been developed for more than 10 years, the following approaches are being adopted to get round this problem: the use of older preparations which have not been used for a long time, the introduction of combinations such as narasin nicarbazin or methyl benzoquate clopidol and the alternating use of anticoccidial agents in rotation and shuttle programmes. The goal of a real alternative, i.e. vaccination, has been achieved to a certain extent in the form of live vaccines for laying hens and broiler breeders and is being practiced in some countries.

Malaria, intestinal parasites, and schistosomiasis among Barawan Somali refugees resettling to the United States: a strategy to reduce morbidity and decrease the risk of imported infections.

In 1997, enhanced health assessments were performed for 390 (10%) of approximately 4,000 Barawan refugees resettling to the United States. Of the refugees who received enhanced assessments, 26 (7%) had malaria parasitemia and 128 (38%) had intestinal parasites, while only 2 (2%) had Schistosoma haematobium eggs in the urine. Mass therapy for malaria (a single oral dose of 25 mg/kg of sulfadoxine-pyrimethamine) was given to all Barawan refugees 1-2 days before resettlement. Refugees >2 years of age and nonpregnant women received a single oral dose of 600 mg albendazole for intestinal parasite therapy. If mass therapy had not been provided, upon arrival in the United States an estimated 280 (7%) refugees would have had malaria infections and 1,500 (38%) would have had intestinal parasites. We conclude that enhanced health assessments provided rapid on-site assessment of parasite prevalence and helped decrease morbidity among Barawan refugees, as well as, the risk of imported infections.

Economic benefits of prophylaxis with diclazuril against subclinical coccidiosis in lambs reared indoors.

One hundred and twenty weaned male lambs, naturally infected with Eimeria species, were used to assess the economic benefits of the prophylactic administration of diclazuril. They were randomly divided into four groups of 30 lambs on the basis of their bodyweight and output of oocysts. The groups were either left untreated (group 1), treated orally with a simple dose of diclazuril at 1 mg/kg (group 2), with two doses two weeks apart (group 3), or with sulphadimethoxine at 50 mg/kg for five consecutive days (group 4). No clinical signs of coccidiosis were observed in any of the groups. The output of oocysts was significantly reduced on day 7 after treatment in group 2, on days 7, 14 and 28 in group 3 and on days 7 and 14 in group 4. No significant differences were found between the treated and untreated groups for bodyweight, carcase weight and carcase classification. The mean fattening period was shorter for the treated lambs (52 and 55 days) than for the untreated controls (60 days). The average growth rate of the lambs treated twice with diclazuril and with sulphadimethoxine was improved and the feed conversion rates of the lambs treated once or twice with diclazuril were 7 per cent and 16 per cent better than that of the untreated lambs.

[The usefulnes of baycox (bayer) for coccidiosis control of lambs]. / Przydatnosc preparatu baycox (bayer) w profilaktyce kokcydiozy u jagniat.

The aim the studies was to establish the usefulness of Baycox for control of coccidiosis and ITS influence on production results (efficiency) in lambs. The studies were carried out on 200 lambs, naturally infected with coccidia, divided in 2 groups -control and experimental, 100 animals in each, after separation from ewes selected in respect of sex, type, date of birth and weight. Toltrazuiril (Baycox) was used the first time for control of sheep coccidiosis in Poland. Toltrazuril was applied individual, twice at 110 and 117 day of life in a doses of 20 mg/kg body weight. The extensity and intensity of coccidia infection was ascertained by the Willis-Schlaaf and McMaster methods. The weight gain of lambs was stated once a month on the basis of individual weight. It was established that toltrazuril show a high efficiency against the protozoa of the genus Eimeria and drug could be used for coccidia control in lambs. This preparation is very active against all intracellular stages - schisogony and gamogony and it could be used for treatment of clinical coccidiosis. It was established profitable influence on the weight gain of lambs.

[Economical consequences of coccidia infection in calves]. / Ekonomiczne konsekwencje kokcydiozy u cielat.

The studies were carried out in two farms - ZZK Kolbacz and SK Bielin, on 60 calves, 30 animals in each farm. The calves ware divided for control and experimental groups -15 animals per group. Baycox was administered two times in 7 days interval in a dosis of 20 mglkg of body weight. The weight gain and the course of coccidia infection in calves before and after traetment with Baycox ware examined. In control animals during the time of studies the coccidia infection was very hight. After administration of Baycox the intensity of coccidia infection was very low and oocysts were found in same animals, only. In SK Bielin before Baycox was used clinical coccidiosis and mortality of 6.9% calves was observed. After Baycox administration 1.9 % animals died, only. The results ware analyst statistically.

The current status of antiparasite chemotherapy.

Currently used antiparasitic drugs, including benzimidazoles, nitroimidazoles, avermectins, polyene ionophores, hydroxynaphthoquinones and sesquiterpene lactones, were identified through the empirical route to drug discovery. The modern rational approach to drug design is focused upon the structure and function of biochemical and molecular targets. The requisite pharmacological properties for new anti-parasite drugs should not be ignored in this process.

Evaluación de la eficacia del salstop y del digestor broilers (citrade C.A.): productos derivados de extractos de semillas de frutas cítricas contra la coccidiosis aviar: prueba en piso / Assessment of salstop and digestor broilers (citrade C.A.) efficacy: citric fruits derivated products against avian coccidiosis: floor test

Orientado hacia la promoción de nuevos productos de actividad anticoccidial, entre otras acciones se evaluó la eficacia de dos productos, Salstop y Digestor Broilers (Citrade CA) para el control de la coccidiosis aviar, en un ensayo en piso con pollos de engorde. Se utilizaron 240 pollitos de 1 día de edad, distribuidos al azar en 6 grupos experimentales, con 4 réplicas c/u de 10 pollitos-réplica: I= Salstop-Inoculado; II= Salstop-No inoculado; III= Digestor Broilers-Inoculado; IV= Digestor Broilers-No Inoculado; V= No medicado-Inoculado (control+) y VI= No Medicado-No Inoculado (control-). Las aves se medicaron vía alimento desde el 1 día de edad, a la dosis de: Salstop 50 g/ton (grupos I y II) y Digestor Broilers 1 kg/ton (grupos III y IV), realizándose el reto parasitario al día 15 de edad de las aves, de manera individual (grupos I, III y V). Se registró datos y cálculos de pesos semanales, ganancias de peso, consumo de alimento, conversión alimenticia, producción e índice de oocystos, score e índice de lesiones, mortalidad, cuadro clínico, índice anticoccidial e índice de productividad Salstop y Digestor Broilers, resultaron con una eficacia moderada contra la coccidiosis aviar al evaluar los índices anticoccidiales y de productividad. Por evidenciarse lesiones severas en el ciego se deduce una nula actividad contra la E. tenella; ambas tuvieron un efecto como promotores del crecimiento