Prior exposure to non‐pathogenic calicivirus RCV‐A1 reduces both infection rate and mortality from rabbit haemorrhagic disease in a population of wild rabbits in Australia

Mortality caused by rabbit haemorrhagic disease virus (RHDV ) in wild rabbits is reduced in parts of Australia where the related, non‐pathogenic calicivirus RCV ‐A1 is endemic. Laboratory experiments previously showed that prior infection with RCV ‐A1 enabled rabbits to better withstand subsequent infection with highly virulent RHDV , and this was assumed to explain higher survival. Here, we analyse serological data from the field suggesting that reduced mortality rates among wild rabbits may also result from rabbits previously infected with RCV ‐A1 having a reduced likelihood of RHDV infection. We discuss the possible mechanisms underlying this finding and its implications. The methods we describe for analysing field data gave far greater insights into epidemiological processes and virus interactions than gained from reporting basic seroprevalence rates alone.     

Corticosteroids and methotrexate as adjuvants to costimulation blockade in non‐human primate renal transplantation

Belatacept, the CD28‐B7 costimulation pathway inhibitor, has been approved as a calcineurin inhibitor (CNI) alternative in kidney transplantation. Although costimulation blockade (CoB) allows for CNI avoidance, it is associated with increased rates of early rejection, prompting a search for agents to pair with belatacept. Methotrexate (MTX) is an antimetabolite that has been found to be complimentary with abatacept, a lower affinity CD28‐B7‐specific analogue of belatacept, in the treatment of rheumatoid arthritis (RA). We examined whether this synergy would extend to prevention of kidney allograft rejection. Rhesus macaques underwent kidney transplantation treated with abatacept maintenance therapy with either a steroid taper, MTX, or both. The combination of abatacept maintenance with steroids prolonged graft survival compared to untreated historical controls and previous reports of abatacept monotherapy. The addition of MTX did not provide additional benefit. These data demonstrate that abatacept with adjuvant therapy may delay the onset of acute rejection, but fail to show synergy between abatacept and MTX beyond that of steroids. These findings indicate that MTX is unlikely to be a suitable adjuvant to CoB in kidney transplantation, but also suggest that with further modification, a CoB regimen used for advanced RA may suffice for RA patients requiring kidney transplantation.     

Non‐tuberculous Mycobacteria in Wild Boar (Sus scrofa) from Southern Spain: Epidemiological,Clinical and Diagnostic Concerns

Non‐tuberculous mycobacteria (NTM) are widely distributed in the environment, particularly in wet soil, marshland, rivers or streams, but also are causative agents of a wide variety of infections in animals and humans. Little information is available regarding the NTM prevalence in wildlife and their effects or significance in the bovine tuberculosis (bTB) epidemiology and diagnosis. This research shows the most frequently NTM isolated in lymph nodes of wild boar (Sus scrofa) from southern Spain, relating the NTM presence with the individual characteristics, the management of animals and the possible misdiagnosis of Mycobacterium bovis in concurrent infections. A total of 219 NTM isolates were obtained from 1249 wild boar mandibular lymph nodes sampled between 2007 and 2011. All but 75 isolates were identified by the PCR‐restriction analysis‐hsp65, and a partial sequencing of the 16S rDNA was carried out to identify the rest of the isolates. Results showed that Mycobacterium chelonae was the most frequently isolated NTM specie (133 isolates, 60.7%), followed by Mycobacterium avium (24 isolates, 11%). No relation was found regarding sex, body condition and management, but M. chelonae was more frequently detected in adults, whereas M. avium was more prevalent in subadults. The high NTM prevalence observed in the studied wild boar populations could make difficult the bTB diagnostic.     

Distinction Between Persistent and Transient Infection in a Bovine Viral Diarrhoea (BVD) Control Programme: Appropriate Interpretation of Real‐Time RT‐PCR and Antigen‐ELISA Test Results

Control of bovine viral diarrhoea (BVD) in Belgium is currently implemented on a voluntary basis at herd level and mainly relies on detection and culling of persistently infected (PI) animals. The present field study was conducted during the winter of 2010/2011 to assess the performances of diagnostic assays used in the testing scheme for BVD as proposed by the two Belgian regional laboratories. Individual blood samples were collected from 4972 animals, and individual samples from the same herd were pooled (maximum of 30 individual samples per pool) and screened for the presence of Bovine Viral Diarrhoea Virus (BVDV)‐specific RNA using a commercial real‐time RT‐PCR test (ADIAGENE). Individual samples from positive pools were then tested in parallel with the same RT‐PCR test and with an antigen‐capture ELISA test (IDEXX) to detect viremic animals. This study demonstrated that individual results differed according to the type of assay used (P < 0.001): 140 animals (2.8%) were positive by RT‐PCR and 72 (1.4%) by antigen‐ELISA. A second blood sample was taken 40 days later from 74 PCR positive animals to detect persistent viremia: 17 (23%) of these were still PCR positive and considered to be PI and the 57 that no longer tested positive were assumed to be transiently infected (TI) animals. All PI animals were positive also by antigen‐ELISA at both time points. Among TI animals, 10 (16%) were positive by antigen‐ELISA at the first but none at the second sampling. A highly significant difference in cycle threshold (C_t) values obtained by RT‐PCR was observed between PI and TI animals. ROC analysis was performed to establish thresholds to confirm with high probability that an animal is PI, based on the result of RT‐PCR test performed on a single individual blood sample.     

The association between killer‐cell immunoglobulin‐like receptor (KIR) and KIR ligand genotypes and the likelihood of BK virus replication after kidney transplantation

BK virus is a common opportunistic post‐transplantation viral infection. Although some risk factors have been studied in this context, the contribution of NK cells has not been assessed in detail. In a group of kidney transplant recipients, we studied the association between (i) the likelihood of BK virus replication during the two‐year period after kidney transplantation and (ii) the genotypes of the killer cell immunoglobulin‐like receptor (KIR) repertoire and their human leukocyte antigen (HLA) ligands. Other clinical factors (such as defective organ recovery and immunosuppressive treatment) were also assessed. BK virus replication was observed in 43 of the 103 recipients (41%). Patients with BK virus replication in the plasma were more likely to display defective organ recovery in the first seven days post‐transplantation. BK virus replication was not associated with Missing KIR ligands. However, BK virus replication was more frequent in patients with responsive NK cells (i.e. when a ligand for activating KIRs was not homozygous in the recipient and present in the donor). Our results suggest that defective organ recovery and the recipient's activating KIR repertoire may be related (depending on HLA ligands present in the couple recipient / donor) to the reactivation of BK virus replication after kidney transplantation.     

Emperor geese (Anser canagicus) are exposed to a diversity of influenza A viruses,are infected during the non‐breeding period and contribute to intercontinental viral dispersal

Emperor geese (Anser canagicus) are endemic to coastal areas within Beringia and have previously been found to have antibodies to or to be infected with influenza A viruses (IAVs) in Alaska. In this study, we use virological, serological and tracking data to further elucidate the role of emperor geese in the ecology of IAVs in Beringia during the non‐breeding period. Specifically, we assess evidence for: (a) active IAV infection during spring staging, autumn staging and wintering periods; (b) infection with novel Eurasian‐origin or interhemispheric reassortant viruses; (c) contemporary movement of geese between East Asia and North America; (d) previous exposure to viruses of 14 haemagglutinin subtypes, including Eurasian lineage highly pathogenic (HP) H5 IAVs; and (e) subtype‐specific antibody seroconversion and seroreversion. Emperor geese were found to shed IAVs, including interhemispheric reassortant viruses, throughout the non‐breeding period; migrate between Alaska and the Russian Far East prior to and following remigial moult; have antibodies reactive to a diversity of IAVs including, in a few instances, Eurasian lineage HP H5 IAVs; and exhibit relatively broad and stable patterns of population immunity among breeding females. Results of this study suggest that emperor geese may play an important role in the maintenance and dispersal of IAVs within Beringia during the non‐breeding period and provide information that may be used to further optimize surveillance activities focused on the early detection of Eurasian‐origin IAVs in North America.     

Serological Evidence Indicates that Foot‐and‐Mouth Disease Virus Serotype O,C and SAT1 are most Dominant in Eritrea

Foot‐and‐mouth disease (FMD) is endemic in Eritrea and in most parts of Africa. To be able to control FMD using vaccination, information on the occurrence of various foot‐and‐mouth disease serotypes in Eritrea is needed. In this cross‐sectional study, 212 sera samples were collected from FMD infected and recovered animals in Eritrea. These samples were tested for the presence of antibodies against FMD non‐structural proteins (NSP) and neutralizing antibodies against six of the seven (all but SAT 3) serotypes of FMD virus (FMDV). Of these, 67.0% tested positive to non‐structural protein antibodies in the FMD NS ELISA. By virus neutralization, FMDV serotype O antibodies were shown to be the most dominant (approximately 50%). Virus neutralization test results indicate that infection with serotype C and SAT 1 might have occurred, although there are no reports of isolation of these two serotypes. Because the samples were not randomly selected, further random serological surveillance in all age group animals is necessary both to estimate the prevalence of FMD in the country and to confirm the serological results with serotype C and SAT 1.     

Modelling the variation in skin‐test tuberculin reactions,post‐mortem lesion counts and case pathology in tuberculosis‐exposed cattle: Effects of animal characteristics,histories and co‐infection

Correctly identifying bovine tuberculosis (bTB ) in cattle remains a significant problem in endemic countries. We hypothesized that animal characteristics (sex, age, breed), histories (herd effects, testing, movement) and potential exposure to other pathogens (co‐infection; BVDV , liver fluke and Mycobacterium avium reactors) could significantly impact the immune responsiveness detected at skin testing and the variation in post‐mortem pathology (confirmation) in bTB ‐exposed cattle. Three model suites were developed using a retrospective observational data set of 5,698 cattle culled during herd breakdowns in Northern Ireland. A linear regression model suggested that antemortem tuberculin reaction size (difference in purified protein derivative avium [PPD a ] and bovine [PPD b ] reactions) was significantly positively associated with post‐mortem maximum lesion size and the number of lesions found. This indicated that reaction size could be considered a predictor of both the extent (number of lesions/tissues) and the pathological progression of infection (maximum lesion size). Tuberculin reaction size was related to age class, and younger animals (<2.85 years) displayed larger reaction sizes than older animals. Tuberculin reaction size was also associated with breed and animal movement and increased with the time between the penultimate and disclosing tests. A negative binomial random‐effects model indicated a significant increase in lesion counts for animals with M. avium reactions (PPD b− PPD a <  0) relative to non‐reactors (PPD b− PPD a =  0). Lesion counts were significantly increased in animals with previous positive severe interpretation skin‐test results. Animals with increased movement histories, young animals and non‐dairy breed animals also had significantly increased lesion counts. Animals from herds that had BVDV ‐positive cattle had significantly lower lesion counts than animals from herds without evidence of BVDV infection. Restricting the data set to only animals with a bTB visible lesion at slaughter (n  = 2471), an ordinal regression model indicated that liver fluke‐ infected animals disclosed smaller lesions, relative to liver fluke‐negative animals, and larger lesions were disclosed in animals with increased movement histories.     

Role of BK virus infection in end‐stage renal disease patients waiting for kidney transplantation – viral replication dynamics from pre‐ to post‐transplant

We report the prevalence of BK virus (BKV) infection before renal transplantation and the dynamics of BKV viremia from pre‐ to post‐transplantation. We assessed 60 kidney transplanted patients from a single cohort in Italy, treated with identical immunosuppressive therapy, for BK viremia at pre‐transplantation, 12 h, and three and six months post‐transplantation. Polymerase chain reaction showed that the prevalence of plasma BKV replication – considered a marker of infection – was 20% in pre‐transplant patients. All pre‐transplant‐positive patients remained positive post‐transplant, whereas the majority of pre‐transplant‐negative patients remained negative. Viremia dynamics classification revealed three clusters of patients: Cluster A++, pre‐transplant‐positive patients (20%) who tested positive at least once post‐transplant; Cluster B?+, pre‐transplant‐negative patients (28%) who tested positive at least once post‐transplant; and Cluster C– –, pre‐transplant‐negative patients (52%) who remained negative throughout. These clusters presented significant differences related to the prevalence of substantially positive patients with high plasma viral load (>10³ copies/mL) in cluster A, but not in donors’ or grafts’ characteristics. We suggest that pre‐transplant viral status should be considered as an additional risk factor for post‐transplant BKV replication. Therefore, pre‐transplant BKV infection screening in kidney transplant patients should be performed for improving planning of personalized immunosuppressant schemes and specific post‐transplant surveillance.