Infected Cattle Research Articles

Formulating an Innovative Emulsion Based on Poloxamer 407 Containing Oregano and Thyme Essential Oils as Alternatives for the Control of Mastitis Caused by Staphylococcus aureus

Antimicrobial resistance poses a significant challenge in human and veterinary medicine, primarily due to the overuse and misuse of antimicrobial agents. This issue is especially problematic when treating bovine mastitis, a prevalent infection in dairy cattle often caused by Staphylococcus aureus. We developed a sterile emulsion incorporating essential oils (EOs) of Origanum vulgare and Thymus vulgaris, known for their antimicrobial properties. The formulation based on poloxamer 407 was designed for intramammary or topical application on bovine teats. The most promising emulsion was subjected to preliminary stability testing at various temperature conditions over a 35-day period, during which its physicochemical characteristics, texture profile, and film-forming capacity were assessed. In vitro assays were used to evaluate its efficacy against both antimicrobial-sensitive and -resistant S. aureus strains. Thymol was identified as the predominant bioactive compound in the EOs. The formulation, containing 10% (w/w) EOs, exhibited antimicrobial activity against all tested strains and remained stable without phase separation. The emulsion demonstrated film-forming properties along with a satisfactory texture profile. These findings suggest that the emulsion has potential as an alternative therapeutic approach for the treatment of antimicrobial-resistant S. aureus infections in bovine mastitis, highlighting the potential of natural compounds in combating AMR. Further clinical studies are necessary to confirm the safety and therapeutic efficacy of the emulsion in vivo.

Haematological and Biochemical Profiles, Including Vitamin A and Zinc Status, in Clinical and Subclinical Oriental Theileriosis in Cattle

Aim: The present study investigated the clinical, haematological and biochemical profiles in cattle infected with Theileria orientalis, correlating disease severity with various parameters. Study Design: A total of 32 clinically ill, 10 subclinically infected, and 10 healthy control animals were included. Place and Duration of Study: Department of Veterinary Epidemiology and Preventive Medicine, College of Veterinary and Animal Sciences, Kerala Veterinary and Animal Sciences University, Pookode, Wayanad, Kerala, between November 2023 to September 2024. Methodology: Theileria piroplasms, observed via Giemsa staining, appeared as thick and thin rods with trailing cytoplasm and annular, pyriform, garland, and signet-ring shapes. PCR amplification of the T. orientalis major piroplasm surface protein (MPSP) yielded a specific 776 bp product in clinically and subclinically infected animals. Results: Haematological analysis revealed significant anaemia and thrombocytopenia in infected groups, without notable changes in leukocyte counts. Serum protein analysis indicated hypoproteinemia and hypoalbuminemia, while liver enzymes, particularly AST, were elevated in clinically infected cattle, suggesting hepatic involvement. Additionally, serum vitamin A and zinc concentrations were significantly lower in infected cattle, underscoring a possible role for oxidative stress in disease pathogenesis. Conclusion: These findings suggest that T. orientalis infection is associated with multi-systemic impacts, including haematological abnormalities, liver damage, and nutrient deficiencies, which are crucial for accurate diagnosis and effective management strategies.

Identification of Mycoplasma Species in Cattle Associated with Bovine Respiratory Disease Mortality.

Approximately 30 distinct Mycoplasma species have been isolated from cattle, but only a few are pathogenic and can cause serious respiratory diseases. Consequently, this study aimed to identify Mycoplasma spp. infections in cattle with bovine respiratory disease (BRD), considering factors such as animal demographics, concurrent infections with other pathogens, post-mortem clinical findings and histological examinations, and seasonality. A total of 326 samples were collected from 322 cattle that had died from BRD in Northwestern Italy. A total of 54 animals (16.8%) tested positive for Mycoplasma spp., and Mycoplasma bovis (n = 22, 40.7%) and Mycoplasma dispar (n = 13, 24.1%) were the most frequently detected species among the examined cattle. Among positive cattle, those aged five months or younger were approximately five times more likely to be infected by Mycoplasma dispar than by Mycoplasma bovis compared to those older than five months (proportional incidence ratio: 5.1, 95% CI 1.2-21.2). The main bacterial pathogens identified in cattle exhibiting co-infection was Pasteurella multocida, whereas the main viral pathogens were BRSV and BoHV-1. Histopathological investigations predominantly revealed catarrhal bronchopneumonia or purulent catarrhal bronchopneumonia among the examined cattle. Finally, Mycoplasma hyopharyngis, a species isolated from the pharyngeal and nasal cavities of pigs so far, was detected for the first time in the pneumonic lung of a bovine infected with BRD. Further investigations are necessary to thoroughly characterize its host range and pathogenic potential.

Avian influenza A (H5N1) virus in dairy cattle: origin, evolution, and cross-species transmission.

Since the emergence of highly pathogenic avian influenza virus (HPAIV) H5N1 of clade 2.3.4.4b as a novel reassortant virus from subtype H5N8, the virus has led to a massive number of outbreaks worldwide in wild and domestic birds. Compared to the parental HPAIV H5N8 clade 2.3.4.4b, the novel reassortant HPAIV H5N1 displayed an increased ability to escape species barriers and infect multiple mammalian species, including humans. The virus host range has been recently expanded to include ruminants, particularly dairy cattle in the United States, where cattle-to-cattle transmission was reported. As with the avian 2.3.4.4.b H5N1 viruses, the cattle-infecting virus was found to transmit from cattle to other contact animals including cats, raccoons, rodents, opossums, and poultry. Although replication of the virus in cows appears to be mainly confined to the mammary tissue, with high levels of viral loads detected in milk, infected cats and poultry showed severe respiratory disease, neurologic signs, and eventually died. Furthermore, several human infections with HPAIV H5N1 have also been reported in dairy farm workers and were attributed to exposures to infected dairy cattle. This is believed to represent the first mammalian-to-human transmission report of the HPAIV H5N1. Fortunately, infection in humans and cows, as opposed to other animals, appears to be mild in most cases. Nevertheless, the H5N1 bovine outbreak represents the largest outbreak of the H5N1 in a domestic mammal close to humans, increasing the risk that this already mammalian adapted H5N1 further adapts to human-to-human transmission and starts a pandemic. Herein, we discuss the epidemiology, evolution, pathogenesis, and potential impact of the recently identified HPAIV H5N1 clade 2.3.4.4b in dairy cattle in the United States. Eventually, interdisciplinary cooperation under a One Health framework is required to be able to control this ongoing HPAIV H5N1 outbreak to stop it before further expansion of its host range and geographical distribution.

Genome sequence of Trueperella pyogenes isolates from liver abscesses in feedlot cattle.

High-grain diets promote polymicrobial liver infections in cattle, commonly involving the bacterium Trueperella pyogenes. We have isolated T. pyogenes from the purulent material of abscesses and sequenced their genomes. These data enhance our understanding of the mechanisms underlying liver abscess development in cattle.

Molecular Detection of Ehrlichia ruminantium in Cattle From Different Agro-Ecological Zones of Cameroon: Implication for the Understanding of the Heartwater Epidemiology.

Although Amblyomma variegatum and Ehrlichia ruminantium infections have been reported in cattle from some agro-ecological zones (AEZs) of Cameroon, the transmission patterns of this bacterium seem to vary according to endemic areas and its prevalence as well as that of Heartwater remains not well understood in most sub-Saharan African countries. This study was designed to detect E. ruminantium infections in cattle of four AEZs of Cameroon and to identify areas presenting enzootic stability and those with potentially high risk for Heartwater. Blood samples were collected from cattle in four AEZs of Cameroon. DNA was extracted from blood and semi-nested PCR targeting the 16S rRNA gene of E. ruminantium was used to search for this bacterium. From 569 cattle analysed, an E. ruminantium DNA fragment was detected in 197 of them, giving an overall prevalence of 34.6%. The highest prevalence of E. ruminantium of 48.0% was recorded in cattle from AEZ IV and the lowest (26.0%) in those from AEZ III. Among the AEZs, significant differences (X2 = 14.85, p = 0.002) were recorded in terms of the prevalence of E. ruminantium infections. Villages of the westerly areas are at higher risk for E. ruminantium infections. This study revealed a high prevalence and a wide distribution of E. ruminantium infections in AEZs of Cameroon. It enabled the identification of areas showing an enzootic stability for E. ruminantium transmission as well as those where the transmission of this bacterium is low and where livestock are at higher risk of developing Heartwater.

Gastrointestinal helminths of Cattle slaughtered at Gwagwalada abattoir, federal capital territory, Nigeria

Gastrointestinal parasites are widespread in cattle worldwide, causing both clinical and sub-clinical infections that can lead to significant financial losses. This study investigated the prevalence of gastrointestinal helminths infection in cattle slaughtered in the abattoir at Gwagwalada area council, federal capital territory, Nigeria. A total of 120 faecal samples were collected and analysed by flotation and sedimentation methods. The results revealed an overall prevalence of 26.67%. The helminths identified were Toxocara sp (5.00%), Schistosoma sp (10.83%), and Fasciola sp (10.83%). These findings were compared to existing studies, with variations attributed to differences in climatic conditions, management practices, and seasonal factors. Age, breed, and sex-specific analyses revealed significant differences in infection rates. While no helminth infection was found in young adult cattle (1≤3 years), a 31.37% prevalence was recorded in older adult cattle (≥3 years). Among the breeds examined, Sokoto Gudali showed the highest prevalence (100%), followed by White Fulani (26.42%) and Red Fulani (16.67%). A significant breed-related difference (p = 0.0001) was recorded. Additionally, male cattle exhibited a higher prevalence (31.37%) compared to (0.00%) in females. The study highlighted the impact of geographical, ecological, and environmental factors on helminths infection, as well as the need for strategic anthelmintic treatment, improved livestock management, and educational programs to control these infections. Regular monitoring and selective breeding may further contribute to long-term infection control in cattle populations.

First molecular evidence of bovine hemoplasmas in houseflies (Musca domestica)

BackgroundHemoplasma infections in cattle are caused by Mycoplasma wenyonii and Candidatus Mycoplasma haemobos and induce asymptomatic or chronic infections but occasionally lead to life-threatening hemolytic anemia. Despite the global distribution of bovine hemoplasmas, information regarding their transmission vectors and prevalence is still lacking in the Republic of Korea. Therefore, this study aims to investigate the infection rate of bovine hemoplasma in cattle and houseflies and to assess the risk factors associated with hemoplasma infection in cattle.MethodsOverall, 376 blood samples were collected from Korean indigenous cattle (male, 10−13 months old), along with 2,690 houseflies (Musca domestica) from the same farm where the cattle were raised. PCR assays targeting the 16S rRNA gene were performed to detect hemoplasmas, and positive samples were sequenced.ResultsThe infection rate of bovine hemoplasmas was 50.8% (191/376) in cattle and 7.4% in pooled houseflies. Among cattle, 18.6% (70/376) and 20.0% (75/376) tested positive for M. wenyonii and Candidatus M. haemobos, respectively. Conversely, in houseflies, Candidatus M. haemobos was more frequently detected (5.9%) than M. wenyonii (0.7%). Co-infection was 12.2% (46/376) in cattle and 0.7% in flies. Furthermore, hemoplasma infection was significantly associated with the grazing experience of their dams. Cattle born to cows with grazing experience exhibited a higher risk for M. wenyonii infection (odds ratio [OR] = 1.62; 95% confidence interval [CI]: 1.03−2.55; P = 0.045), whereas these cattle had a lower risk for Candidatus M. haemobos infection (OR = 0.32, 95% CI: 0.19−0.74; P = 0.000) than animals born to cows without grazing experience. The sequences obtained from houseflies were confirmed as Candidatus M. haemobos, which displayed high similarity (98.2−100%) to those from cattle obtained in this study.ConclusionsTo our knowledge, this study represents the first report of bovine hemoplasmas identified in houseflies. This molecular evidence suggests that houseflies may be possible vectors for Candidatus M. haemobos.

Source attribution of Listeria monocytogenes in the Netherlands

The aim of this study was to determine the relative contributions of various potential food sources of human listeriosis and to identify source-specific risk factors, at exposure level, for human Listeria monocytogenes (Lm) infection. To achieve this, available Lm isolates from human cases (n = 756) and food/animal sources (n = 950) from national surveillance systems in the Netherlands (2010−2020) were whole genome sequenced. Additionally, questionnaire-based exposure data for human cases was collected. Source attribution analysis was performed using a Random Forest model based on core-genome multilocus sequence typing (cgMLST). Risk factors for human Lm infection of cattle, chicken and seafood origin were determined using beta regression analysis on the cgMLST-based attribution estimates. Results indicated that the 756 human Lm isolates were mainly attributed to cattle (62.3 %), chicken (19.4 %), and seafood (16.9 %). Specifically, fresh meat (86.2 %), including fresh bovine meat (43.7 %) and fresh chicken meat (39.3 %), accounted for most cases. These attributions stemmed from Lm contamination of either the food products or their production environments. Consumption of steak tartare and smoked salmon was associated with an increased risk of human Lm infections attributed to cattle and seafood, respectively, while no specific risk factors for chicken-borne listeriosis were identified. This study indicated that Lm isolates of cattle origin, particularly those from fresh bovine meat and associated production environments, are estimated to be the primary cause of human listeriosis in the Netherlands. This aligns with several other European source attribution studies on Lm. Moreover, the identified risk factors for human Lm infection from cattle (i.e. steak tartare) and seafood (i.e. smoked salmon) clearly indicated their attributable sources. This joint analysis of core genome and epidemiological data provided novel insights into the origins and transmission pathways of human listeriosis.

A Molecular Approach to Understand the Involvement of Mycoplasma in Suppurative Otitis Cases of Cattle in Chittoor District of Andhra Pradesh

In bovines the economic losses mainly due to the outbreak of diseases, leads to mortality, morbidity, treatment cost and reduced production. Recently in August month of 2024, received 13 bovine suppurativeotitis samples from outbreak in KuppamMandal of Chittoor district. The history having the purulent discharges with foul smell from ear infections of cattle that to crossbreed cattle of all age groups are affected. After 5 days of appearing aural discharges the animals were also shown the nervous signs, head tilting and other clinical findings includes unilateral or bilateral ear droop, epiphora, ptosis, abnormal nystagmus, strabismus, regurgitation, stiff neck, opisthotonus, facial hyperesthesia, purulent aural discharge, nasopharyngeal collapse, recumbency and finally death were noticed in severely affected animals. All the samples were processed for cultural tests by inoculating in PPLO selective broth and selective media PPLO agar then incubated anaerobically at 370C and observed the color development in broth pink to yellow color after 3- 5 days of incubation indicative of positive growth and fried egg micro colonies on selective PPLO agar media after 8-14 days of incubation observed under low power and 40X. The DNA was isolated from all the samples and screened for presence of Mycoplasma by targeting 16s rRNA gene and found that out of 13 samples 10 were positive for genus Mycoplasma and produced the predicted 280bp size product in all positive samples. The suppurativeotitis in cattle usually is caused by Actinomyces spp., Corynebacterium pseudotuberculosis, E. coli, Heamophilus, P.multocida, Pseudomonas spp, Streptococcus spp., and Mycoplasma bovis. This study was targeted only the emerging pathogen i.e the cellwall deficient bacteria Mycoplasma because of infections is hampered by a lack of effective vaccines and specific treatments, leads to increasing trends in antimicrobial resistance. Concluded that isolation and identification of the pathogenic ........

Structure-based virtual screening and drug repurposing studies indicate potential inhibitors of bovine papillomavirus E6 oncoprotein.

Bovine papillomavirus type 1 (BPV1) is an oncogenic virus that causes lesions and cancer in infected cattle. Despite being one of the most studied genotypes in the family and occurring in herds worldwide, there are currently no vaccines or drugs for its control. The viral E6 oncoprotein plays a crucial role in infection by this virus, making it a promising target for the development of new therapies. In this regard, we integrated structure-based virtual screening approaches, drug repositioning, and molecular dynamics to identify approved drugs with the potential to inhibit BPV1 E6. Our results reveal that Lumacaftor and MK-3207 are promising candidates for controlling BPV1 infection. The findings of this study may contribute to the development of E6 oncoprotein blockers in an accelerated and cost-effective manner.

Discovery of Mycobacterium avium subsp. paratuberculosis Lytic Phages with Extensive Host Range Across Rapid- and Slow-Growing Pathogenic Mycobacterial Species.

Developing interventions for Johne's disease, which focuses on controlling Mycobacterium avium subsp. paratuberculosis (MAP) in contaminated environments by treating infected cows and preventing transmission from diseased animals, is a critical priority. Bacteriophage (phage) therapy, an emerging biological intervention, offers a promising alternative for the treatment and management of MAP infections. In this study, we generated an MAP-specific lytic phage library aimed at characterizing the therapeutic potential of phages under environmental and biological conditions that mimic those encountered in infected cattle such as ruminal fluid, milk, colostrum, and the bovine intestinal epithelium, a key site of MAP colonization and, later, transmission. Our library contains a diverse collection of phages that have demonstrated robust lytic activity against MAP. The host range of these phages was thoroughly assessed, revealing that several isolates produce clear plaques on a range of MAP strains, as well as other pathogenic non-tuberculous mycobacterial (NTM) species and M. tuberculosis strains. This broad host range expands the therapeutic potential of the phage collection, positioning it as a potential cross-species antimicrobial tool. In vitro tests under conditions replicating the rumen, milk, and colostrum environments show that selected phages maintain stability and lytic efficacy, even in the presence of complex biological fluids. Furthermore, a subset of these phages was capable of preventing MAP colonization and invasion in cultured bovine epithelial cells, suggesting their potential for direct prophylactic application in cattle. Our collection of MAP phages represents a valuable source that can be developed into probiotic-like preparations, offering a cost-effective solution for prophylaxis and control of Johne's disease.

A Combination of Chemotherapy and Autogenous Vaccine for Control of Bovine Papillomatosis in Cattle

The present study was conducted during the period from July, 2023 to January, 2024. Two clinical cases of cattle were reported with cutaneous papillomas, one near right umbilical region and another over the right hind teat of cattle. Both the animals were treated with a protocol designed such that it can regulate the secondary bacterial infection, speedy recovery of integument system and enhance the immune response for complete regression of the warts. The innate immune responses of infected animals were augmented with inactivated pathogen associated molecular patterns (PAMPs) as autogenous vaccine candidate. The warts were surgically excised, triturated in sterile PBS, inactivated with 0.5% formaline and prepared the autogenous vaccine. The sterility test of vaccine revealed that the vaccine was free from bacterial and fungal contaminants. The chemotherapy includes the use of drugs Thuja ointment, Inj.Enrofloxacin, Inj.Avil and Inj.Anthiomaline. The dose of the vaccine was 1 ml 20 kg-1 b.wt. subcutaneously and given at weekly intervals for a period of 4 weeks. It was observed that the treatment protocol was successfully effective and regression of warts was noticed from 2nd week onwards. By end of 4th week a complete recovery of the wart infected area was noticed with a black scar left behind. The formalin inactivated autogenous vaccine was effective, and applied for control of bovine papillomavirus infection in cattle with combination of chemotherapeutic drugs resulted in early regression of warts.

The Pharmacokinetics of Subcutaneous Eprinomectin in Plasma and Milk in Dry Dairy Cattle.

Parasitic infections in dairy cattle reduce herd immunity, milk production, and conception rates. This leads to higher production costs, compromised animal welfare, and increased interest in extralabel drug use. The extralabel use of anthelmintics poses food safety risks for consumers since appropriate withdrawal intervals in milk have yet to be established. Although topical eprinomectin has no milk withdrawal time, more research is needed to determine the residues present in milk after subcutaneous administration. This study aimed to characterize the pharmacokinetics of injectable eprinomectin in dry dairy cows. We hypothesized that, when given at the labeled dose, eprinomectin residues in dry dairy cattle would be below the FDA milk tolerance at the onset of lactation. Plasma was collected daily from 13 mature dairy cattle for 7 days postadministration, followed by periodic samples for 90 days. After calving, milk was collected daily until 90 days. Eprinomectin concentrations were measured using HPLC-fluorescence detection. The maximum eprinomectin concentration in plasma and milk was approximately 36 ng/mL 43 h after administration and 3 ng/mL at the onset of lactation, respectively. The low eprinomectin levels in milk collected from these lactating dairy cattle suggest that administering eprinomectin at dry-off is unlikely to result in violative residues. However, subcutaneous eprinomectin in lactating dairy cattle would be hard to justify unless there is evidence that the approved topical formulation is clinically ineffective.

A comprehensive and single-use foot-and-mouth disease sero-surveillance prototype employing rationally designed multiple viral antigens

Foot-and-mouth disease (FMD) is a great havoc in agri-business-based countries like Bangladesh, for which existing detection system limits the identification and differentiation of serotypes. In this study, an engineered platform was introduced incorporating serotype-specific FMDV VP1 (structural), serotype-independent VP2 (structural) and 3AB (non-structural) proteins for holistic detection. VP1 sequences were engineered combining sequences of BAN/TA/Dh-301/2016 (serotype O), BAN/CH/Sa-304/2016 (serotype A) and BAN/DH/Sa-318/2016 (serotype Asia1). Consensus 3AB sequence was constructed from the selected prevalent viral genomes. Both VP1 and 3AB along with designed VP2 sequences were optimized for codon usage bias, stable mRNA, secondary and tertiary protein structure. Proteins were synthesized in pET-21a ( +) plasmid vector followed by transformation of Escherichia coli BL21(DE3) and IPTG-induced- expression. The western blot analysis of engineered proteins showed that purified VP1 prominently bound to anti-VP1 antibodies in vaccinated sera, whereas 3AB and VP2 bound anti-3AB and anti-VP2 antibodies, respectively from infected cattle sera, all previously collected during epidemiological investigation. Furthermore, dot blot hybridization confirmed efficient antibody capture ability of the membrane-immobilized proteins. This holistic diagnostic platform justifies a comprehensive prototype diagnostic kit that would be cost-effective and efficient for serotype specific and non-specific FMDV sero-surveillance.

Serological evidence of tick-borne Crimean-Congo haemorrhagic fever and Dugbe orthonairovirus infections in cattle in Kwara State in northern Nigeria indicate independent endemics.

Crimean-Congo haemorrhagic fever orthonairovirus (CCHFV) and Dugbe orthonairovirus (DUGV) are zoonotic viruses transmitted by ticks. Whereas CCHFV has caused numerous human cases, DUGV, although less reported, shares ticks and ruminants as hosts. Since its first discovery in Nigeria in 1964, there has been no detailed sero-epidemiological investigation on DUGV in sub-Saharan Africa. This study is aimed at assessing the current seroprevalence and associated risk factors of CCHFV and DUGV infections in Nigerian cattle. Using a cross-sectional design with random sampling method, blood samples were collected from 877 cattle on pastoralist farms and at abattoirs in Kwara State, North-Central Nigeria. CCHFV IgG antibodies were detected in extracted sera using three panels of in-house indirect enzyme-linked immunosorbent assay (ELISA) based on bacteria-expressed recombinant nucleoprotein (rNP), the cattle-adapted VectoCrimean ELISA and the ID Screen CCHF double antigen multi-species ELISA, while DUGV IgG antibodies were detected using in-house indirect ELISA with bacteria-expressed rNP, indirect immunofluorescence assay and micro-Virus Neutralization test. Overall seroprevalence rates of 71.9% (631/877) and 52.8% (451/854) were obtained for CCHFV and DUGV, respectively. It was observed that 37.9% (314/829) of the cattle were co-exposed to both CCHFV and DUGV while 34.5% (286/829), 14.8% (123/829) and 12.8% (106/829) were exposed to single infections with CCHFV, DUGV or none of the two viruses, respectively. Multivariate analysis showed that only location, sex, age and tick infestation score were the risk factors that significantly affected CCHFV seroprevalence in cattle, while DUGV seroprevalence was significantly influenced by month of the year, location, cattle breed and sex (p<0.05). This is the first comprehensive sero-epidemiological surveillance for DUGV in sub-Saharan Africa. Our findings reveal widely distributed independent CCHFV and DUGV infections in cattle in Kwara State, Nigeria.

A surface lipoprotein on Pasteurella multocida binds complement factor I to promote immune evasion.

Pasteurella multocida is the leading cause of wound infections in humans following animals' bites or scratches. This bacterium is also commonly found in the respiratory tract of many mammals and can cause serious diseases resulting in the brutal rapid death of infected animals, especially cattle. To prevent these infections in cattle, a subunit-based vaccine utilizing the surface lipoprotein PmSLP was developed and showed remarkable protection with a single dose administration. Here, we report that PmSLP binds host complement factor I (FI) and facilitates cleavage of complement components C3b and C4b independently of any cofactors (e.g FH, C4BP), thereby allowing the pathogen to evade host defence. Cryo-EM structure of PmSLP bound to FI reveals that PmSLP stimulates FI enzymatic activity by stabilizing the catalytic domain. This is the first time that a bacterial protein has been shown to directly activate FI independent of complement cofactors and target all arms of the complement cascade.

Field Trial with Vaccine Candidates Against Bovine Tuberculosis Among Likely Infected Cattle in a Natural Transmission Setting.

Background/Objectives: Vaccines may improve the control and eradication of bovine tuberculosis. However, the evaluation of experimental candidates requires the assessment of the protection, excretion, transmission and biosafety. A natural transmission trial among likely infected animals was conducted. Methods: Seventy-four male heifers were randomly distributed (five groups) and vaccinated subcutaneously with attenuated strains (M. bovis Δmce2 or M. bovis Δmce2-phoP), a recombinant M. bovis BCG Pasteur (BCGr) or M. bovis BCG Pasteur. Then, they cohoused with a naturally infected bTB cohort under field conditions exposed to the infection. Results: A 23% of transmission of wild-type strains was confirmed (non-vaccinated group). Strikingly, first vaccination did not induce immune response (caudal fold test and IFN-gamma release assay). However, after 74 days of exposure to bTB, animals were re-vaccinated. Although their sensitization increased throughout the trial, the vaccines did not confer significant protection, when compared to the non-vaccinated group, as demonstrated by pathology progression of lesions and confirmatory tools. Besides, the likelihood of acquiring the infection was similar in all groups compared to the non-vaccinated group (p > 0.076). Respiratory and digestive excretion of viable vaccine candidates was undetectable. To note, the group vaccinated with M. bovis Δmce2-phoP exhibited the highest proportion of animals without macroscopic lesions, compared to the one vaccinated with BCG, although this was not statistically supported. Conclusions: This highlights that further evaluation of these vaccines would not guarantee better protection. The limitations detected during the trial are discussed regarding the transmission rate of M. bovis wild-type, the imperfect test for studying sensitization, the need for a DIVA diagnosis and management conditions of the trials performed under routine husbandry conditions. Re-vaccination of likely infected bovines did not highlight a conclusive result, even suggesting a detrimental effect on those vaccinated with M. bovis BCG.

Comparative pathogenesis of Ethiopia/Habru/2014 Lineage-IV peste des petits ruminants virus in goats and cattle

BackgroundPeste des Petits Ruminants (PPR) is a highly contagious viral disease primarily affecting goats and sheep, with clinical manifestations ranging from peracute disease to subclinical infection, particularly in atypical hosts such as cattle. The role of atypical hosts such as cattle to the spread of PPR remains controversial, with conflicting reports in the literature. Despite its worldwide significance, considerable knowledge gaps exist regarding the pathogenesis and clinical progression in both primary and atypical hosts. This study aimed to elucidate the tissue tropism, pathogenesis, virus shedding, clinical progression, and pathology associated with experimental PPR virus infection in indigenous goats and cattle. To this end, 32 animals—16 goats and 16 cattle—were intranasally inoculated with the Ethiopia/Habru/2014 Lineage-IV strain of the PPR virus followed by detailed clinical evaluations and systematic sampling at pre-established intervals to assess serological conversion, viral shedding, and the pathogenesis of the infection across both species.ResultsThe results show that goats exhibited typical clinical signs 4 days post-inoculation, with seroconversion by day 6 and early detection of viral RNA in swabs and tissues by day 3 and virus isolation starting day 4. In contrast, cattle exhibited minimal clinical signs, with seroconversion occurring at day 8 with viral RNA detected in tissue samples at day 4 and virus isolation starting day 6 in tissues and in a single nasal swab at day 8. Clinical scores and tissue positivity rates significantly differed between goats and cattle (P = 0.007 and P < 0.001, respectively). While goats exhibited expected gross and histopathological lesions, cattle showed only nonspecific lesions.ConclusionsTogether, our findings highlight the importance of comparative pathology studies for better understanding virus dynamics and transmission pathways that may help inform more effective PPR control programs. Future research should explore the pathogenesis of different PPRV lineages in cattle, assessing variations in disease progression and potential for epidemiological impact.

Effect of C-to-T transition at CpG sites on tumor suppressor genes in tumor development in cattle evaluated by somatic mutation analysis in enzootic bovine leukosis.

Oncogenic transformation of normal cells is caused by mutations and chromosomal abnormalities in cancer-related genes. Enzootic bovine leukosis (EBL) is a malignant B-cell lymphoma caused by bovine leukemia virus (BLV) infection in cattle. Although a small fraction of BLV-infected cattle develops EBL after a long latent period, the mechanisms for oncogenesis in EBL cattle remain largely unknown. In this study, we analyzed the types and patterns of somatic mutations in cancer cells from 36 EBL cases, targeting 21 cancer-related genes. Various somatic mutations were identified in eight genes, TP53, KMT2D, CREBBP, KRAS, PTEN, NOTCH1, MYD88, and CARD11. In addition, TP53 gene was found to be mutated in 69.4% of EBL cases, with most being biallelic mutations. In some cases, associations were observed between the ages at which cattle had developed EBL and somatic mutation patterns; young onset of EBL possibly occurs due to high impact mutations affecting protein translation and biallelic mutations. Furthermore, nucleotide substitution patterns indicated that cytosine at CpG sites tended to be converted to thymine in many EBL cases, which was considered to be the result of spontaneous deamination of 5-methylcytosine. These results demonstrate how somatic mutations have occurred in cancer cells leading to EBL development, thereby explaining its pathogenic mechanism. These findings will contribute to a better understanding and future elucidation of disease progression in BLV infection.IMPORTANCEEnzootic bovine leukosis (EBL) is a malignant and lethal disease in cattle. Currently, there are no effective vaccines or therapeutic methods against bovine leukemia virus (BLV) infection, resulting in severe economic losses in livestock industry. This study provides a renewed hypothesis to explain the general mechanisms of EBL onset by combining the previous finding that several integration sites of BLV provirus can affect the increase in survival and proliferation of infected cells. We demonstrate that two additional random events are necessary for oncogenic transformation in infected cell clones, elucidating the reason why only few infected cattle develop EBL. Further exploration of somatic mutation and BLV integration sites could support this hypothesis more firmly, potentially contributing to the development of novel control methods for EBL onset.