Efficacy of a Neospora caninum killed tachyzoite vaccine in preventing abortion and vertical transmission in dairy cattle

Weston, J F; Heuer, C; Williamson, N. B.

doi:10.1016/j.prevetmed.2011.08.010

Cited by 56 publications

(45 citation statements)

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“…Neoguard, a killed tachyzoite lysate and the only vaccine that has been marketed to date, was reported in one publication to reduce the abortion rate in cattle by approximately 50% [6] but does not induce protection against fetal infection in cattle. However, more recent trials revealed fewer efficacies in the field, and even suggested that vaccination may increase the risk of early embryonic death [7]. Thus, the vaccine has been taken off the market.…”

Section: Introductionmentioning

confidence: 99%

Neospora caninum Calcium-Dependent Protein Kinase 1 Is an Effective Drug Target for Neosporosis Therapy

et al. 2014

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Despite the enormous economic importance of Neospora caninum related veterinary diseases, the number of effective therapeutic agents is relatively small. Development of new therapeutic strategies to combat the economic impact of neosporosis remains an important scientific endeavor. This study demonstrates molecular, structural and phenotypic evidence that N. caninum calcium-dependent protein kinase 1 (NcCDPK1) is a promising molecular target for neosporosis drug development. Recombinant NcCDPK1 was expressed, purified and screened against a select group of bumped kinase inhibitors (BKIs) previously shown to have low IC50s against Toxoplasma gondii CDPK1 and T. gondii tachyzoites. NcCDPK1 was inhibited by low concentrations of BKIs. The three-dimensional structure of NcCDPK1 in complex with BKIs was studied crystallographically. The BKI-NcCDPK1 structures demonstrated the structural basis for potency and selectivity. Calcium-dependent conformational changes in solution as characterized by small-angle X-ray scattering are consistent with previous structures in low Calcium-state but different in the Calcium-bound active state than predicted by X-ray crystallography. BKIs effectively inhibited N. caninum tachyzoite proliferation in vitro. Electron microscopic analysis of N. caninum cells revealed ultra-structural changes in the presence of BKI compound 1294. BKI compound 1294 interfered with an early step in Neospora tachyzoite host cell invasion and egress. Prolonged incubation in the presence of 1294 interfered produced observable interference with viability and replication. Oral dosing of BKI compound 1294 at 50 mg/kg for 5 days in established murine neosporosis resulted in a 10-fold reduced cerebral parasite burden compared to untreated control. Further experiments are needed to determine the PK, optimal dosage, and duration for effective treatment in cattle and dogs, but these data demonstrate proof-of-concept for BKIs, and 1294 specifically, for therapy of bovine and canine neosporosis.

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Section: Introductionmentioning

confidence: 99%

Neospora caninum Calcium-Dependent Protein Kinase 1 Is an Effective Drug Target for Neosporosis Therapy

et al. 2014

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“…The treatment option (with 75 toltrazuril (Kritzner et al, 2002)) has been identified as expensive in cattle and is potentially 76 fraught with issues of milk and meat residues. Vaccines appear to be the favoured control 77 option and the subject of a considerable body of research (Liddell et al, 1999; Miller et al, 78 2005) ), a vaccine which had demonstrated 81 little more than 60% efficacy at best, and whose efficacy may have been as low as 25% 82 (Weston et al, 2012), there are now only few management options available. 83…”

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confidence: 99%

What is the global economic impact of Neospora caninum in cattle – The billion dollar question

Reichel

Ayanegui-Alcérreca

Gondim

et al. 2013

International Journal for Parasitology

423

281

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Graphical Abstract (for review) Click here to download high resolution image Bullet points A systematic review of literature conducted after Pubmed search for Neospora and cattle  Modelling after review suggests that the cost of N caninum globally exceeds one billion dollars  Approximately two thirds of the costs of N caninum are incurred by dairy industries world-wide  Analysis of the regional distribution of global costs of N caninum highlights the cattle industries of the North American as incurring two thirds of the overall global cost  At the farm level, costs only exceed US$ 2,000 in four countries Neospora caninum is regarded as one of the most important infectious causes of abortions in 20 cattle world-wide, yet the global economic impact of the infection has not been established. 21A systematic review of the economic impact of N caninum infections/abortions was 22 conducted, searching PubMed with the terms cattle and Neospora. This yielded 769 23 publications whose abstracts were screened for economically relevant information (e.g. 24 abortion prevalence and risk, serological prevalence). Further analysis was restricted to 25 countries with at least 5 relevant publications. In total, 99 studies (12.9%) from ten countries 26 contained data from the beef industry (25 papers (25.3%)) and 72 papers (72.8%) from the 27 dairy industry (with the remainder two papers (2.0%) describing general abortion statistics). 28The total annual cost of N caninum infections/abortions was estimated to range from a 29 median US $1.1 million in the New Zealand beef industry to an estimated median total of 30 US$ 546.3 million impact per annum in the US dairy population. The estimate for the total 31 median N caninum-related losses exceeded US$ 1.298 billion per annum, ranging as high as 32 US$ 2.380 billion. Nearly two thirds of the losses were incurred by the dairy industry (US$ 33 842.9 million). Annual losses on individual dairy farms were estimated to reach a median of 34 US$ 1,600.00, while on beef farms these costs amounted to just US$ 150.00. Pregnant cows 35 and heifers were estimated to incur, on average, a loss due to N caninum of less than 36 US$20.00 for dairy, and less than US$ 5.00 for beef. These loss estimates, however rose to 37 ~US$ 110.00 and US$ 40.00, respectively for N caninum-infected pregnant dairy and beef 38 cows. This estimate of global losses due to N caninum, with the identification of clear target 39 markets (countries, as well as cattle industries), should provide incentive to develop 40 treatment options and/or vaccines. 41 42 Keywords: Neospora caninum, abortion, cattle, costs, economics, dairy, beef 43 3 Introduction 44Neospora caninum is recognised world-wide as an important infectious cause of 45 abortion in primarily cattle, and of clinical disease in dogs (Dubey and Schares, 2011). 46 Infection with N caninum is frequent in canid populations (Barber et al., 1997; Reichel, 47 1998); also recently reviewed by Al-Qassab et al. (2010)) yet clinical cases in dogs are rarely 48report...

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“…However, live vaccination, of attenuated N. caninum strain (NC-Nowra Ò ) demonstrate higher efficacy but may suffer as a commercial product from limited shelf-life and high production cost. Most studies published to date have focused on the evaluation of subunit recombinant vaccines from tachyzoites proteins for their vaccine potential despite the fact that it is still not clear whether this tachyzoites contains protective antigens (Weston et al 2012). …”

Section: Vaccinationmentioning

confidence: 99%

The common zoonotic protozoal diseases causing abortion

Shaapan

2015

J Parasit Dis

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Toxoplasmosis, neosporosis, sarcosporidiosis (sarcocystosis) and trypanosomiasis are the common zoonotic protozoal diseases causing abortion which caused by single-celled protozoan parasites; Toxoplasma gondii, Neospora caninum, Sarcocystis spp and Trypanosoma evansi, respectively. Toxoplasmosis is generally considered the most important disease that causing abortion of both pregnant women and different female animals throughout the world, about third of human being population had antibodies against T. gondii. The infection can pass via placenta, causing encephalitis, chorio-retinitis, mental retardation and loss of vision in congenitally-infected children and stillbirth or mummification of the aborted fetuses of livestock. Neosporosis is recognized as a major cause of serious abortion in varieties of wild and domestic animals around the world particularly cattle, the disease cause serious economic losses among dairy and beef cattle due to decrease in milk and meat production. While unlike toxoplasmosis, neosporosis is not recognized as a human pathogen and evidence to date shows that neosporosis is only detected by serology in the human population. Sarcosporidiosis also can cause abortion in animals particularly cattle, buffaloes and sheep with acute infection through high dose of infection with sarcocysts. On the other hand, humans have been reported as final and intermediate host for sarcosporidiosis but not represent a serious health problem. Trypanosomiasis by T. evansi cause dangerous infection among domestic animals in tropical and subtropical areas. Several cases of abortion had been recorded in cattle and buffaloes infected with T. evansi while, a single case of human infection was reported in India. Trichomoniasis and babesiosis abortion occurs with non-zoonotic Trichomonas and Babesia species while the zoonotic species had not been incriminated in induction of abortion in both animals and man. The current review article concluded that there is still need of wide scope for evaluation of the zoonotic impact and control of these diseases.

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Efficacy of a Neospora caninum killed tachyzoite vaccine in preventing abortion and vertical transmission in dairy cattle

Cited by 56 publications

References 44 publications

Neospora caninum Calcium-Dependent Protein Kinase 1 Is an Effective Drug Target for Neosporosis Therapy

Neospora caninum Calcium-Dependent Protein Kinase 1 Is an Effective Drug Target for Neosporosis Therapy

What is the global economic impact of Neospora caninum in cattle – The billion dollar question

The common zoonotic protozoal diseases causing abortion

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