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Mannheimia haemolytica is the major cause of severe pneumonia in bovine respiratory disease (BRD). Early M. haemolytica bacterins were either ineffective or even enhanced disease in vaccinated cattle, which led to studies of the bacterium's virulence factors and potential immunogens to determine ways to improve vaccines. Studies have focused on the capsule, lipopolysaccharide, various adhesins, extracellular enzymes, outer membrane proteins, and leukotoxin (LKT) resulting in a strong database for understanding immune responses to the bacterium and production of more efficacious vaccines. The importance of immunity to LKT and to surface antigens in stimulating immunity led to studies of individual native or recombinant antigens, bacterial extracts, live-attenuated or mutant organisms, culture supernatants, combined bacterin-toxoids, outer membrane vesicles, and bacterial ghosts. Efficacy of several of these potential vaccines can be shown following experimental M. haemolytica challenge; however, efficacy in field trials is harder to determine due to the complexity of factors and etiologic agents involved in naturally occurring BRD. Studies of potential vaccines have led current commercial vaccines, which are composed primarily of culture supernatant, bacterin-toxoid, or live mutant bacteria. Several of those can be augmented experimentally by addition of recombinant LKT or outer membrane proteins.

The reported incidences of co-participation of Mycoplasma capricolum capripneumoniae (Mccp) and Pasteurella multocida in increased severity and pathogenesis of goats with Contagious caprine pleuropneumonia (CCPP) in sub-Saharan Africa elicited the study’s purpose. Using the preferred reporting items for systematic review and meta-analysis (PRISMA) guideline, two search engines, namely Google Scholar and PubMed, were queried to systematically review all the available literature on the current epidemiological status of CCPP and Pneumonic Pasteurellosis co-concurrently detected in goats and assess the available treatment and control measures and their challenges in the Sub-Saharan region. The search was limited to papers published between 1998 and 2024, whereby only peer-reviewed English articles were included in the study. Review papers, papers displaying abstracts only, duplicated information, papers beyond the sub-Saharan Africa region and papers published in other languages were excluded from the study. Only articles with full text and focused on goats were included for further screening process and review. A total of 3311 articles were retrieved from both databases, whereas only 58 articles met the inclusion criteria and hence were included in the data analysis. Only eight countries namely, Ethiopia, Kenya, Uganda, Nigeria, Sudan, Eritrea, Zambia and Tanzania reported the occurrence of CCPP and or Pasteurellosis: Ethiopia 23/58(39%), Tanzania 18/58 (31%), 1/58(2%) Nigeria, 1/58(2%) Zambia, 1/58(2%) Eritrea, Uganda 2/58 (3%), 2/58(3%) Sudan and Kenya 10/58(16%). Only 5/58 (9%) reported the occurrence of pneumonic pasteurellosis in Nigeria and Ethiopia. Only Tanzania (75%) and Ethiopia (33%) reported Mccp and Pasteurella multocida co-isolation and/ or detection in CCPP cases. Information on the antimicrobial susceptibility profile of Mccp and Pasteurella multocida from Sub-Saharan Africa was unavailable. One vaccine against CCPP, namely F-38 inactivated, and one vaccine against pneumonic pasteurellosis were identified to be developed and used in Sub-Saharan Africa. Developing bivalent candidate vaccines for both etiological agents is highly recommended.

Mannheimia haemolytica is recognized as principal pathogen associated with pneumonic pasteurellosis leading to huge economic losses to small ruminant farmers. Even though the disease causes huge economic losses, epidemiology of M. haemolytica is less studied, hindering the formulation of effective control strategies. Current study aimed to highlight molecular characterisation of M. haemolytica strains isolated from ovine pneumonic infection. M. haemolytica 27 isolates with two reference strains were characterised using capsular and virulence gene typing, multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) methods. M. haemolytica serotype A2 recognized as predominant serotype (74%) followed by A6 (11%) and A1 (5%) serotypes. Virulence gene profiling by PCRs showed dominance of all five virulent genes [such as adh and gcp (100% each)] followed by gs60 (88.8%), lktC (85.2%), tbpB (51.9%) and least nmaA gene (14.8%). MLST profiling delineated M. haemolytic isolates into 11 sequence types (STs) with most prevalent being ST37 (27.9%) and ST16 (23%) and nine new STs (ST37, 38, 39, 40, 41, 42, 47, 48, and 49). These new STs did not belong to any of the three clonal complexes (CC4, CC8 and CC28). ST16 was exclusively noted in A1 and A6 serotypes. Amongst 25 isolates, 22 pulsotypes (GD 0.88) recorded indicated variability of the M. haemolytica isolates in PFGE analysis. In conclusion, the study suggested dominance of M. haemolytica serotype A2 harbouring different virulent genes, diverse STs and pulsotypes responsible for pneumonic pasteurellosis frequently encountered in sheep.

Background Pneumonic pasteurellosis leads to substantial economic losses in the small ruminant Production because of high mortality and reduced productivity. A cross‐sectional study was employed with the objective to isolate and identify Mannheimia haemolytica and Pasteurella multocida from outbreak cases of small ruminants in selected districts of Afar region, Ethiopia from December 2021 to June 2023. A total of 192 nasal swab samples were collected using purposive sampling technique and bacterial isolation and identification was carried out as per the standard bacteriological methods. Descriptive statistics and Pearson's chi‐square (χ2) were employed to check the association between occurrence of the disease and associated risk factors and statistical significance was set at p < 0.05. Results In the current study, the overall bacterial isolation rate from clinical cases of ovine and caprine pneumonic pasteurellosis was found to be 24.48% (n = 47/192), of which M. haemolytica accounted for 17.19% (n = 33/192) of bacterial isolates, while P. multocida accounted for 7.29% (n = 14/192) from isolates recovered from nasal swabs. Moreover, the present study also indicated that goats were more affected by this disease with the bacterial occurrence rate of 32.86% (n = 23/70) as compared to sheep with 19.67% (n = 24/122) in the study districts. There was statistically significant difference across species (p = 0.041) of the study animals with occurrence of the ovine and caprine pasteurellosis in nasal swabs. The study further revealed significant variation in the incidence rates of presumptive Pasteurella isolates across the study areas with Asayita recording the highest rate at 19.70% (n = 13/66), followed by Dubti at 17.46% (n = 11/63), and Mille at 14.29% (n = 9/63) even though no statistical association was observed. Conclusions The present study finding indicated that M. haemolytica is the predominant bacterium associated with pneumonic pasteurellosis in ovine and caprine in the study areas. This could highlights the need for developing a polyvalent vaccine incorporating M. haemolytica strains. • The present study finding indicated that M. haemolytica is the predominant bacterium associated with pneumonic pasteurellosis in ovine and caprine in the study areas. • Goats were found to be significantly more susceptible than sheep. • This could suggest the need for developing a polyvalent vaccine incorporating M. haemolytica strains.

This clinical trial evaluated the impact of metaphylactic antimicrobial administration 10 d before experimental inoculation with Mannheimia haemolytica (MH) to mitigate pulmonary lesions. Thirty-three crossbreed heifers were procured as a single group and were randomly allocated to 1 of 3 blocks and to treatment, tildipirosin (ZUP; 4 mg/kg) or tulathromycin (DRX; 2.5 mg/kg) or saline (SAL; 1 mL/45.5 kg), within block on arrival at Kansas State University. All trial procedures were staggered by 7-d intervals for each block, resulting in all animals within a block receiving treatment, challenge, and necropsy on the same dates. Heifers within each block received an endoscopic MH challenge 10 d following treatment administration (d 0) and were housed in individual indoor stalls for 3 d postchallenge. Clinical illness scores (CIS), respiration quality scores, appetite scores, and injection site reactions were recorded on all animals from d 0 through d 13. Rectal temperatures were measured once daily on all animals from d 8 through d 13. Heifers were necropsied, and lung lesions were evaluated on d 13. Lung lesion data were evaluated using nonparametric methods (Kruskall-Wallis), and standard least squares models were used to evaluate the remaining variables. The pulmonary lesion scores (percentage of affected lung) ranged from 3.3% to 39.8% for all heifers with 92% (11/12) of ZUP-treated heifers having <10% lesions. Tildipirosin-treated heifers had lower (P < 0.05) lung lesion scores when compared with DRX- and SAL-treated heifers. Lung weight expressed as a percentage of BW was lower (P < 0.05) in ZUP heifers compared to DRX- and SAL-treated heifers. The probability of receiving abnormal CIS, appetite scores, and respiratory scores was lower (P < 0.05) in ZUP-treated heifers compared to DRX- and SAL-treated animals. This study showed that heifers treated with tildipirosin 10 d before MH challenge have less pulmonary damage and fewer clinical signs of illness compared to heifers treated with DRX or SAL.

► Cross protection by bovine respiratory disease vaccine against M. haemolytica A6. ► Live attenuated vaccine containing M. haemolytica A1 and P. multocida. ► Model induced severe challenge involving P. multocida. ► Resulted in reduced clinical scores mortality and lung lesions. Bovine respiratory disease causes significant economic losses in both beef and dairy calf industries. Although multi-factorial in nature, the disease is characterized by an acute fibrinous lobar pneumonia typically associated with the isolation of Mannheimia haemolytica. M. haemolytica A1 and A6 are the two most commonly isolated serotypes from cattle, however, the majority of vaccines have not demonstrated cross-serotype protection. In the current study, the efficacy of a novel, attenuated live vaccine, containing both M. haemolytica serotype A1 and Pasteurella multocida, was evaluated in calves challenged with M. haemolytica serotype A6. Although the challenge was more severe than expected, vaccinated calves had reduced clinical scores, lower mortality, and significantly lower lung lesion scores compared to the placebo-vaccinated control group. The results demonstrate that vaccination with an attenuated live vaccine containing M. haemolytica serotype A1 can protect calves against clinical disease following challenge with M. haemolytica serotype A6.

Background Detection of respiratory viruses in veterinary species has traditionally relied on virus detection by isolation or immunofluorescence and/or detection of circulating antibody using ELISA or serum neutralising antibody tests. Multiplex real time PCR is increasingly used to diagnose respiratory viruses in humans and has proved to be superior to traditional methods. Bovine respiratory disease (BRD) is one of the most common causes of morbidity and mortality in housed cattle and virus infections can play a major role. We describe here a one step multiplex reverse transcriptase quantitative polymerase chain reaction (mRT-qPCR) to detect the viruses commonly implicated in BRD. Results A mRT-qPCR assay was developed and optimised for the simultaneous detection of bovine respiratory syncytial virus (BRSV), bovine herpes virus type 1 (BoHV-1) and bovine parainfluenza virus type 3 (BPI3 i & ii) nucleic acids in clinical samples from cattle. The assay targets the highly conserved glycoprotein B gene of BoHV-1, nucleocapsid gene of BRSV and nucleoprotein gene of BPI3. This mRT-qPCR assay was assessed for sensitivity, specificity and repeatability using in vitro transcribed RNA and recent field isolates. For clinical validation, 541 samples from clinically affected animals were tested and mRT-qPCR result compared to those obtained by conventional testing using virus isolation (VI) and/or indirect fluorescent antibody test (IFAT). Conclusions The mRT-qPCR assay was rapid, highly repeatable, specific and had a sensitivity of 97% in detecting 10 2 copies of BRSV, BoHV-1 and BPI3 i & ii. This is the first mRT-qPCR developed to detect the three primary viral agents of BRD and the first multiplex designed using locked nucleic acid (LNA), minor groove binding (MGB) and TaqMan probes in one reaction mix. This test was more sensitive than both VI and IFAT and can replace the aforesaid methods for virus detection during outbreaks of BRD.

Pasteurella multocida is a pathogenic Gram-negative bacterium that has been classified into three subspecies, five capsular serogroups and 16 serotypes. P. multocida serogroup A isolates are bovine nasopharyngeal commensals, bovine pathogens and common isolates from bovine respiratory disease (BRD), both enzootic calf pneumonia of young dairy calves and shipping fever of weaned, stressed beef cattle. P. multocida A:3 is the most common serotype isolated from BRD, and these isolates have limited heterogeneity based on outer membrane protein (OMP) profiles and ribotyping. Development of P. multocida-induced pneumonia is associated with environmental and stress factors such as shipping, co-mingling, and overcrowding as well as concurrent or predisposing viral or bacterial infections. Lung lesions consist of an acute to subacute bronchopneumonia that may or may not have an associated pleuritis. Numerous virulence or potential virulence factors have been described for bovine respiratory isolates including adherence and colonization factors, iron-regulated and acquisition proteins, extracellular enzymes such as neuraminidase, lipopolysaccharide, polysaccharide capsule and a variety of OMPs. Immunity of cattle against respiratory pasteurellosis is poorly understood; however, high serum antibodies to OMPs appear to be important for enhancing resistance to the bacterium. Currently available P. multocida vaccines for use in cattle are predominately traditional bacterins and a live streptomycin-dependent mutant. The field efficacy of these vaccines is not well documented in the literature.

The goal of this study was to assess the diagnostic accuracy of acute phase proteins and proinflammatory cytokines in sheep with pneumonic pasteurellosis. Blood samples were collected from 56 sheep (36 naturally infected with Pasteurella multocida and 20 healthy controls) belonging to one farm in Eastern region, Saudi Arabia. Serum samples were evaluated for acute phase proteins (Haptoglobin (Hp), serum amyloid A (SAA) and fibrinogen (Fb)), and the proinflammatory cytokines (interleukins (IL-1 α , IL-1 β , and IL-6), tumor necrosis factor-alpha (TNF- α ), and interferon-gamma (IFN-ϒ)). Additionally, nasopharyngeal swabs and bronchoalveolar lavages were collected from all animals for bacteriological examinations. Receiver operating characteristic curve was used to assess the diagnostic performance of each parameter. All parameters showed moderate to high degree of positive correlation with case-control status. There was no significant difference in the area under the curve (AUC) among acute phase proteins; however, both Hp and SAA showed better sensitivity and specificity than Fb. The proinflammatory cytokines (IL1- α , IL1- β , and IL6) showed similar and highly accurate diagnostic performance ( AUC > 0.9), whereas IFN-ϒ was moderately accurate ( AUC = 0.79). In conclusion, this study confirms the value of acute phase proteins and cytokines as diagnostic biomarkers of naturally occuring pneumonic pasteurellosis in sheep.

Mannheimia haemolytica is a Gram negative bacterium that is part of the bovine respiratory disease, which causes important economic losses in the livestock industry. In the present work, the interaction between M. haemolytica A1 and bovine lactoferrin (BLf) was studied. This iron-chelating glycoprotein is part of the mammalian innate-immune system and is present in milk and mucosal secretions; Lf is also contained in neutrophils secondary granules, which release this glycoprotein at infection sites. It was evidenced that M. haemolytica was not able to use iron-charged BLf (BholoLf) as a sole iron source; nevertheless, iron-lacked BLf (BapoLf) showed a bactericidal effect against M. haemolytica with MIC of 4.88 ± 1.88 and 7.31 ± 1.62 μM for M. haemolytica strain F (field isolate) and M. haemolytica strain R (reference strain), respectively. Through overlay assays and 2-D electrophoresis, two OMP of 32.9 and 34.2 kDa with estimated IP of 8.18 and 9.35, respectively, were observed to bind both BapoLf and BholoLf; these OMP were identified by Maldi-Tof as OmpA (heat-modifiable OMP) and a membrane protein (porin). These M. haemolytica BLf binding proteins could be interacting in vivo with both forms of BLf depending on the iron state of the bovine.