Contagious Bovine Pleuropneumonia: A Comprehensive Overview.

Contagious bovine pleuropneumonia (CBPP) is a respiratory disease of cattle that is listed as notifiable by the World Organization for Animal Health. It is endemic in sub-Saharan Africa and causes important productivity losses due to the high mortality and morbidity rates. CBPP is caused by Mycoplasma mycoides subsp. mycoides (Mmm) and is characterized by severe fibrinous bronchopneumonia and pleural effusion during the acute to subacute stages and by pulmonary sequestra in chronic cases. Additional lesions can be detected in the kidneys and in the carpal and tarsal joints of calves. Mmm infection occurs through the inhalation of infected aerosol droplets. After the colonization of bronchioles and alveoli, Mmm invades blood and lymphatic vessels and causes vasculitis. Moreover, Mmm can be occasionally demonstrated in blood and in a variety of other tissues. In the lung, Mmm antigen is commonly detected on bronchiolar and alveolar epithelial cells, in lung phagocytic cells, within the wall of blood and lymphatic vessels, inside necrotic areas, and within tertiary lymphoid follicles. Mmm antigen can also be present in the cytoplasm of macrophages within lymph node sinuses, in the germinal center of lymphoid follicles, in glomerular endothelial cells, and in renal tubules. A complete pathological examination is of great value for a rapid presumptive diagnosis, but laboratory investigations are mandatory for definitive diagnosis. The purpose of this review is to describe the main features of CBPP including the causative agent, history, geographic distribution, epidemiology, clinical course, diagnosis, and control. A special focus is placed on gross and microscopic lesions in order to familiarize veterinarians with the pathology and pathogenesis of CBPP.

Interleukin-17 mediates lung injury by promoting neutrophil accumulation during the development of contagious caprine pleuropneumonia.

Contagious caprine pleuropneumonia (CCPP) is a highly contagious infectious disease of goats caused by Mycoplasma capricolum subspecies capripneumoniae (Mccp). CCPP outbreaks usually result in high morbidity and mortality of the affected goats, making this disease a major cause of economic losses to goat producers globally. However, the pathogenesis of CCPP remains unclear. Here, we show that IL-17-driven neutrophil accumulation is involved in the lung damage in CCPP goats. During CCPP development, intense inflammatory infiltrates could be observed in the injured lungs. Specifically, neutrophils were observed to be present within the alveoli. Increased IL-17 release drove the excessive influx of neutrophils into the lung, as IL-17 effectively stimulated the production of neutrophil chemoattractants from lung epithelial cells following Mccp infection. Our data highlight a critical role of IL-17-driven neutrophil accumulation in the pathogenesis of CCPP and suggest that IL-17 may potentially be a useful immunotherapeutic target for the treatment of CCPP.

Lung lesion score system in cattle: proposal for contagious bovine pleuropneumonia.

Contagious bovine pleuropneumonia (CBPP) is a severe infectious disease caused by Mycoplasma mycoides subsp. mycoides. The peculiar pathological features of CBPP make desirable the assessment of ad hoc score methods to grade the disease in the affected animals. Thus, the present work aims to assess a new lung score system for CBPP. Our results indicate that the present score system strongly correlates with that previously published by Turner and could be effectively used in CBPP-affected animals.

The Association of Fibrinous Pleural Effusion with Survival and Complications in Horses with Pleuropneumonia (2002-2012): 74 Cases.

BACKGROUND: Fibrinous parapneumonic pleural effusions are associated with decreased efficacy of pleural fluid drainage and increased risk of medical treatment failure in people, but similar associations have not been established in horses. HYPOTHESIS/OBJECTIVES: We hypothesized that fibrin deposition in the pleural cavity of horses with parapneumonic effusions increases the risk of poor outcome. ANIMALS: Seventy four horses with bacterial pleuropneumonia diagnosed by culture and cytology of tracheal aspirates, pleural fluid, or both, and pleural effusion diagnosed by ultrasonographic examination. METHODS: Retrospective study of cases was from 2002 to 2012. Information obtained from the medical records included signalment, history, sonographic findings, treatments, and outcome. The primary outcome investigated was survival and secondary outcomes were development of complications and surgical intervention. Fisher's exact test and logistic regression were applied for categorical variables. A t-test was used to find differences in continuous variables between groups. RESULTS: Seventy four horses met study criteria and 50 (68%) survived. Fibrinous pleural effusion was associated with higher respiratory rate and pleural fluid height at admission, necrotizing pneumonia, increased number of indwelling thoracic drains required for treatment, and decreased survival. CONCLUSIONS AND CLINICAL IMPORTANCE: Fibrin accumulation in parapneumonic effusions is associated with increased mortality. Direct fibrinolytic treatment might be indicated in affected horses.

High antibody titres against predicted Mycoplasma surface proteins do not prevent sequestration in infected lung tissue in the course of experimental contagious bovine pleuropneumonia.

Contagious bovine pleuropneumonia (CBPP), a severe respiratory disease of cattle caused by Mycoplasma mycoides subsp. mycoides (Mmm) is endemic in many African countries due to fragmented veterinary services and the lack of an efficient vaccine and sensitive diagnostics. More efficient tools to control the disease are needed, but to develop the tools, a better understanding of host-pathogen interactions is necessary. The aim of this study was to characterize the kinetics of the humoral immune response against 65 Mmm surface antigens for an extended period in cattle that survived a primary infection with Mmm. We describe clinical and haematological outcomes, and dissect the humoral immune response over time, to specific antigens and compared the antibody responses between different pathomorphological outcomes. No antigen-specific antibodies correlating with protection were identified. Interestingly we found that animals that developed Mycoplasma-containing sequestra had significantly higher antibody levels against proteins comprising the surface proteome than the animals that cleared Mycoplasma from their lungs. Based on these data we suggest that high antibody titres might play a role in the establishment of pathomorphological changes, such as vasculitis, which should be investigated in future studies. Beneficial antibody specificities and cellular immune responses need to be identified in order to foster the development of an improved vaccine in the future.

Efficacy of two vaccine formulations against contagious bovine pleuropneumonia (CBPP) in Kenyan indigenous cattle.

A live, attenuated vaccine is currently the only viable option to control of CBPP in Africa. It has been suggested that simple modifications to current vaccines and protocols might improve efficacy in the field. In this report we compared the current vaccine formulation with a buffered preparation that maintains Mycoplasma viability at ambient temperature for a longer time. Groups of animals were vaccinated with the two formulations and compared with non vaccinated groups. Half of the animals in each group were challenged 3 months post vaccination, the other half after 16 months. Protection levels were measured using the pathology index, calculated from post mortem scores of lesions from animals killed during the course of clinical disease. In the challenge at 3 months post vaccination, the protection levels were 52% and 77% for the modified and current vaccine preparations, respectively. At 16 months post vaccination, the protection levels were 56% and 62% for the modified and current vaccine preparations, respectively. These findings indicate that there are no differences in protection levels between the two vaccines. Because of its longer half life after reconstitution, the modified vaccine might be preferred in field situations where the reconstituted vaccine is likely not to be administered immediately.

Caprine pleuropneumonia in Beetal goats [corrected].

Seroprevalence, clinical findings, and lesions of contagious caprine pleuropneumonia (CCPP) in Beetal goats were recorded during an outbreak. The overall seroprevalence of CCPP was 32.50%. Confirmation of Mycoplasma mycoides in serum was carried out using counter immunoelectrophoresis (CIE) technique. The highest CIE-positive cases were recorded in the older goats (51.72%) as compared to young ones. Nasal swabs collected from 39 goats showing respiratory signs were found positive for M. mycoides. The most consistent clinical findings were mild to severe cough, purulent nasal secretion, emaciation, dyspnea, increased respiration rate, and pyrexia. Mortality due to CCPP was 9.17%. Consolidation of lungs exhibited the highest frequency (100%), followed by alveolar exudation (90.90%) and pleural adhesion (72.72%). Among the microscopic lesions, septal peribronchiolar fibrosis exhibited the highest frequency (81.81%), followed by fibrinous pleuritis (63.63%) and peribronchiolar cuffing of mononuclear cells (54.54%) in lungs. From these results, it was concluded that CCPP under subtropical conditions has high prevalence in Beetal goats and leads to significant mortality.

Fatal outbreak of Mycoplasma capricolum pneumonia in endangered markhors.

A pneumonia outbreak reduced the numbers of a wild population of endangered markhors (Capra falconeri) in Tajikistan in 2010. The infection was diagnosed by histologic examination and bacteriologic testing. Mycoplasma capricolum subsp. capricolum was the sole infectious agent detected. Cross-species transmission from domestic goats may have occurred.

Meningitis caused by Mycoplasma mycoides subspecies capri in a goat.

A 2-year-old, female goat from Connecticut was submitted for necropsy with a 5-day history of pyrexia and intermittent neurologic signs, including nystagmus, seizures, and circling. Postmortem examination revealed suppurative meningitis. Histologic examination of the brain revealed that the meninges were diffusely infiltrated by moderate numbers of lymphocytes, macrophages, and fibrin, with scattered foci of dense neutrophilic infiltrate. Culture of pus and brainstem yielded typical mycoplasma colonies. DNA sequencing of the 16S ribosomal RNA gene revealed 99% sequence homology with Mycoplasma mycoides subspecies capri and Mycoplasma mycoides subspecies mycoides Large Colony biotype, which are genetically indistinguishable and likely to be combined as a single subspecies labeled M. mycoides subsp. capri. The present case is unusual in that not only are mycoplasma an uncommon cause of meningitis in animals, but additionally, in that all other reported cases of mycoplasma meningitis in goats, systemic lesions were also present. In the present case, meningitis was the only lesion, thus illustrating the need to consider mycoplasma as a differential diagnosis for meningitis in goats.

Comparison of isolates of Mycoplasma mycoides subspecies capri from asymptomatic and septicaemic goats.

Strains of Mycoplasma mycoides subspecies capri (Mmc) are frequently isolated from goats with contagious agalactia, but they can also be recovered from herds that have shown no clinical signs of mycoplasmosis for several years. The present study was conducted in order to explore the potential genetic and antigenic differences existing between an Mmc strain isolated from an outbreak (septicaemic) and a strain isolated from the ear canal of a goat belonging to a herd with no recent episode of mycoplasmosis (carriage strain). The genomes of the two strains, compared by suppression subtractive hybridization, were shown to be poorly divergent. The two strains were inoculated into goats to produce specific antisera, but both induced fatal mycoplasmosis. These results indicate that septicaemic and carriage strains cannot be distinguished by their genetic background or by their pathogenic capacity under experimental conditions.

Characterization of Mycoplasma isolated from an ibex (Capra ibex) suffering from keratoconjunctivitis in northern Italy.

In 2005 a Mycoplasma species was isolated from ocular-conjunctival swabs from an adult male Alpine ibex (Capra ibex) from the Valle d'Aosta Region, Northern Italy. The animal suffered from bilateral ocular discharge with diffuse inflammation, severe corneal involvement of the left eye and mild corneal opacity of the right eye. Histologic examination revealed a keratoconjunctivitis characterized by lymphocytic and plasmacellular infiltration. Laboratory investigations of the isolate included culture, transmission electron microscopy, PCR, and denaturing gradient gel electrophoresis, as well as DNA sequencing of the 16S rDNA gene. These tests identified the isolate as Mycoplasma mycoides subsp. capri large-colony serovar, an organism that has occasionally been associated with keratoconjunctivitis in goats. For a correct diagnosis, it is necessary to carry out laboratory investigations, as clinical cases of keratoconjunctivitis in wild ruminants are not always ascribable to Mycoplasma conjunctivae.

Protein-specific analysis of humoral immune responses in a clinical trial for vaccines against contagious bovine pleuropneumonia.

Specific humoral immune responses in a clinical trial on cattle for vaccines against contagious bovine pleuropneumonia (CBPP) were investigated. The trial included a subunit vaccine consisting of five recombinant putative variable surface proteins of the infectious agent Mycoplasma mycoides subsp. mycoides small colony type (M. mycoides SC) compared to the currently approved attenuated vaccine strain T1/44 and untreated controls. Humoral immune responses to 65 individual recombinant surface proteins of M. mycoides SC were monitored by a recently developed bead-based array assay. Responses to the subunit vaccine components were found to be weak. Animals vaccinated with this vaccine were not protected and had CBPP lesions similar to those of the untreated controls. In correlating protein-specific humoral responses to T1/44-induced immunity, five proteins associated with a protective immune response were identified by statistical evaluation, namely, MSC_1046 (LppQ), MSC_0271, MSC_0136, MSC_0079, and MSC_0431. These five proteins may be important candidates in the development of a novel subunit vaccine against CBPP.

Experimental infection of goats with an unusual strain of Mycoplasma mycoides subsp. capri isolated in Jordan.

Goats were infected experimentally with a mycoplasma (the "Irbid" strain) isolated previously from a goat with contagious agalactia in northern Jordan. The strain was unusual in that, although it had been identified by molecular methods as Mycoplasma mycoides subsp. mycoides LC/Mycoplasma mycoides subsp. capri, it showed no inhibition of growth by any of the hyperimmune rabbit antisera conventionally used to speciate members of the Mycoplasma mycoides cluster. Animals were infected either intratracheally or by aerosol and placed "in-contact" with other goats. After 2 weeks, those infected intratracheally became febrile, showing a nasal discharge and slight conjunctivitis, followed a week later by respiratory distress and polyarthritis; lesions seen at necropsy included coagulative necrotic pneumonia, fibrinous pleurisy with pleural exudate, and inflammatory exudates, necrosis and fibrosis in the joints. Animals infected by aerosol showed much milder clinical signs, including nasal discharge and occasional swollen joints. In the "in-contact" goats, seroconversion was first seen after 7 weeks, accompanied by coughing and laboured respiration; lesions in this group consisted of fibrinous pneumonia with focal areas of necrosis and abundant pleural exudate.

Clinical, humoral and IFNgamma responses of cattle to infection with Mycoplasma mycoides var. mycoides small colony and attempts to condition the pathogenesis of the infection.

Contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides var. mycoides small colony (MmmSC), is one of the most important diseases of cattle in Africa. The role of innate or acquired cell mediated and humoral immunity in conferring protection against MmmSC infection has not yet been elucidated. On the other hand, the pathological lesions caused by the aetiological agent have been considered indicative of an immunopathological process. In this study ten naïve cattle were exposed to in-contact infection with animals infected by intubation with a strain of MmmSC. Clinical signs, antibody response, IFNgamma release and pathological changes at necropsy were analysed and compared with the events following in-contact infection of an equal number of animals kept under daily treatment with cyclosporine for the entire observation period of 84 days. Cyclosporine is a suppressor of the immune response related to the T-cell system. Under the conditions of the experiment, cyclosporine appeared to condition the pathogenesis of CBPP by delaying the events that follow infection, bringing further support to the possibility that the immune response may have an impact on the disease outcome.

Contagious caprine pleuropneumonia outbreak in captive wild ungulates at Al Wabra Wildlife Preservation, State of Qatar.

Contagious caprine pleuropneumonia (CCPP) caused by Mycoplasma capricolum subsp. capripneumoniae is a highly contagious and serious respiratory disease of domestic goats, characterized by coughing, severe respiratory distress, and high mortality rates. The lesions at necropsy are mainly a fibrinous pleuropneumonia with increased straw-colored pleural fluid. An outbreak of CCPP in wild goat (Capra aegagrus), Nubian ibex (Capra ibex nubiana), Laristan mouflon (Ovis orientalis laristanica), and gerenuk (Litocranius walleri) occurred at Al Wabra Wildlife Preservation in the State of Qatar. The disease was suspected because of the clinical symptoms and the necropsy findings and was confirmed by the isolation and identification of the causative organism. This new finding indicates that CCPP should be considered a potential threat to wildlife and the conservation of endangered ruminant species, especially in the Middle East, where it is enzootic because of its presence in chronic carriers. Susceptible imported animals should be quarantined and vaccinated. The preferred samples for diagnosis are the pleural fluid, which contains high numbers of Mycoplasma, and sections of hepatized lung, preferably at the interface of normal and diseased tissues. Samples must be shipped to diagnostic laboratories rapidly, and appropriate cool conditions must be maintained during shipping.

Ulcerative balanitis and vulvitis of Dorper sheep in South Africa: a study on its aetiology and clinical features.

Ovine ulcerative balanitis and vulvitis in sheep of the Dorper breed has been observed in South Africa since 1979. Its aetiology has not been conclusively resolved, and there is some discrepancy in descriptions of its clinical features. In order to identify the pathogenic micro-organism/s that contribute to the occurrence of the disease, the microflora in the genital tracts of both clinically healthy and affected sheep were isolated and compared. Bacteriological examination of materials from affected and unaffected sheep resulted in the isolation of Arcanobacterium pyogenes from 44.2% and 17.2% of them respectively. This difference is statistically significant (P < 0.01). Seventy-four per cent of the isolates originated from severe clinical cases. Mycoplasmas were isolated from 49.3% of 116 clinically normal sheep and 78.2% of 104 affected sheep. There were significant differences in their rates of isolation in clinical groups (P < 0.05). Of all the mycoplasma isolates, Mycoplasma mycoides mycoides large colony variant (MmmLC) was isolated from 61.5% of clinically diseased sheep while 6.0% of the isolates were from apparently healthy animals (P < 0.05). The study threw light on the prevalence of mycoplasmas in the genital tract of apparently healthy sheep and, at the same time the identity of the mycoplasma pathogen associated with ulcerative balanitis and vulvitis was revealed. The findings of this investigation therefore confirmed the involvement of mycoplasma, particularly that of MmmLC large colony, in the disease in Dorper sheep in South Africa, and it was concluded that this microorganism is an important pathogen of balanitis and vulvitis in them. The study furthermore demonstrated a probable synergism between A. pyogenes and MmmLC. Finding these 2 organisms together occurred 53.4 times more frequently in the affected sheep than in the unaffected, which emphasises the probable multifactorial nature of the disease. The association between age and the presence of clinical signs was statistically significant. It was found that young sheep were more likely to have lesions than adult sheep. Clinical observations showed that the typical ulceration appears to be confined to the glans penis and lips of the vulva; no ulceration was observed on the shaft of the penis and prepuce or vaginal vestibule. In uncomplicated cases inflammation of the prepuce and vaginal vestibule is not a regular feature of the disease. Therefore the names ulcerative balanitis and vulvitis most accurately describe the nature of the disease in South Africa.

Experimental contagious caprine pleuropneumonia: a long term study on the course of infection and pathology in a flock of goats infected with Mycoplasma capricolum subsp. capripneumoniae.

Contagious caprine pleuropneumonia (CCPP) is a major threat to goat farming in parts of Africa and Asia. It classically causes acute high morbidity and mortality early in infection, but little is known of its long term epizootiology and course. In this study, 10 goats were inoculated with Mycoplasma capricolum subsp. capripneumoniae (M. capripneumoniae) and then mixed with 15 goats for contact transmission. The disease course was monitored in each goat for 56-105 days, whereafter the goats were killed and necropsied. Varying features signifying infection occurred in altogether 17 goats (7 inoculated, 10 in-contact). Clinical signs were severe in 8 goats but no fatalities occurred. Only 6 goats had serum antibody titres against M. capripneumoniae in ELISA. Fourteen goats (5 inoculated, 9 in-contact) had chronic pleuropulmonary lesions compatible with CCPP at necropsy and 7 of those showed M. capripneumoniae antigen in the lung by immunohistochemistry. Neither cultivation nor PCR tests were positive for the agent in any goat. The results indicate that the clinical course of CCPP in a flock may be comparatively mild, M. capripneumoniae-associated lung lesions may be present at a late stage of infection, and chronic infection may occur without a significant serological response.

Experimental field trial with an immunostimulating complex (ISCOM) vaccine against contagious bovine pleuropneumonia.

The experimental field trial with an immunostimulating complex (ISCOM) vaccine has been an occasion to explore the role of a Th1 response in the pathogenesis caused by Mycoplasma mycoides subsp. mycoides small colony (MmmSC) and in immune protection. The ISCOM complex is known to promote Th1 response. Antibodies to MmmSC were detected by indirect enzyme-linked immunosorbent assay (ELISA) in the vaccinated cattle, although the levels were lower than in a previous study. No antibodies were detected by complement fixation test (CF). After the challenge infection, vaccinated animals developed CF antibody response. They showed significantly reduced mortality compared with controls. However, gross pathological and histopathological score for vaccinated animals was as high as for the non-vaccinated, characterized by a high inflammatory reaction with histopathology dominated by interlobular pneumonia with vasculitis.