Determinants of protection against SARS-CoV-2 Omicron BA.1 and Delta infections in fully vaccinated outpatients.

We aimed to evaluate the association between the humoral and cellular immune responses and symptomatic SARS-CoV-2 infection with Delta or Omicron BA.1 variants in fully vaccinated outpatients. Anti-receptor binding domain (RBD) IgG levels and interferon-gamma (IFN-γ) release were evaluated at PCR-diagnosis of SARS-CoV-2 in 636 samples from negative and positive patients during Delta and Omicron BA.1 periods. Median levels of anti-RBD IgG in positive patients were significantly lower than in negative patients for both variants (p < 0.05). The frequency of Omicron BA.1 infection in patients with anti-RBD IgG concentrations ≥1000 binding antibody units (BAU)/mL was 51.0% and decreased to 34.4% in patients with concentrations ≥3000 BAU/mL. For Delta infection, the frequency of infection was significantly lower when applying the same anti-RBD IgG thresholds (13.3% and 5.3% respectively, p < 0.05). In addition, individuals in the hybrid immunity group had a 4.5 times lower risk of Delta infection compared to the homologous vaccination group (aOR = 0.22, 95% CI: [0.05-0.64]. No significant decrease in the risk of Omicron BA.1 infection was observed in the hybrid group compared to the homologous group, but the risk decreased within the hybrid group as anti-RBD IgG titers increased (aOR = 0.08, 95% CI: [0.01-0.41], p = 0.008). IFN-γ release post-SARS-CoV-2 peptide stimulation was not different between samples from patients infected (either with Delta or Omicron BA.1 variant) or not (p > 0.05). Our results show that high circulating levels of anti-RBD IgG and hybrid immunity were independently associated with a lower risk of symptomatic SARS-CoV-2 infection in outpatients with differences according to the infecting variant (www.clinicaltrials.gov; ID NCT05060939).

The increasing age of respiratory syncytial virus-related hospitalisation during COVID-19 pandemic in Lyon was associated with reduced hospitalisation costs.

BACKGROUND: Preventive measures applied during the COVID-19 pandemic have modified the age distribution, the clinical severity and the incidence of Respiratory Syncytial Virus (RSV) hospitalisations during the 2020/21 RSV season. The aim of the present study was to estimate the impact of these aspects on RSV-associated hospitalisations (RSVH) costs stratified by age group between pre-COVID-19 seasons and 2020/21 RSV season. METHODS: We compared the incidence, the median costs, and total RSVH costs from the national health insurance perspective in children < 24 months of age during the COVID-19 period (2020/21 RSV season) with a pre-COVID-19 period (2014/17 RSV seasons). Children were born and hospitalised in the Lyon metropolitan area. RSVH costs were extracted from the French medical information system (Programme de Médicalisation des Systémes d'Information). RESULTS: The RSVH-incidence rate per 1000 infants aged < 3 months decreased significantly from 4.6 (95 % CI [4.1; 5.2]) to 3.1 (95 % CI [2.4; 4.0]), and increased in older infants and children up to 24 months of age during the 2020/21 RSV season. Overall, RSVH costs for RSVH cases aged below 2 years old decreased by €201,770 (31 %) during 2020/21 RSV season compared to the mean pre-COVID-19 costs. CONCLUSIONS: The sharp reduction in costs of RSVH in infants aged < 3 months outweighed the modest increase in costs observed in the 3-24 months age group. Therefore, conferring a temporal protection through passive immunisation to infants aged < 3 months should have a major impact on RSVH costs even if it results in an increase of RSVH in older children infected later in life. Nevertheless, stakeholders should be aware of this potential increase of RSVH in older age groups presenting with a wider range of disease to avoid any bias in estimating the cost-effectiveness of passive immunisation strategies.

Effect of a recent parenteral dexamethasone and ketoprofen administration on the immunological diagnosis of tuberculosis in goats.

Caprine tuberculosis (TB) is a zoonosis caused by members of the Mycobacterium tuberculosis complex (MTBC). Caprine TB eradication programmes are based mainly on intradermal tuberculin tests and slaughterhouse surveillance. Different factors may affect the performance of the TB diagnostic tests used in caprine herds and, therefore, their ability to detect infected animals. The present study evaluates the effect of the fraudulent administration of two anti-inflammatory substances, dexamethasone and ketoprofen, on the performance of the TB diagnostic techniques used in goats, as well as the suitability of high performance liquid chromatography (HPLC) for their detection in hair samples. The animals (n = 90) were distributed in three groups: (1) a group treated with dexamethasone (n = 30); a second group treated with ketoprofen (n = 30); and a third non-treated control group (n = 30). Both dexamethasone and ketoprofen groups were subjected to intramuscular inoculation with the substances 48 h after the administration of bovine and avian purified protein derivatives (PPDs), that is, 24 h before the tests were interpreted. All the animals were subjected to the single and comparative intradermal tuberculin (SIT and CIT, respectively) tests, interferon-gamma release assay (IGRA) and P22 ELISA. The number of SIT test reactors was significantly lower in the dexamethasone (p = 0.001) and ketoprofen (p < 0.001) groups 72 h after the bovine PPD inoculation compared with the control group. A significantly higher number of positive reactors to IGRA was detected within the dexamethasone group (p = 0.016) 72 h after PPD administration compared to the control group. Dexamethasone and ketoprofen detection in either hair or serum samples was challenging when using HPLC since these substances were not detected in animals whose skin fold thickness (SFT) was reduced, what could be an issue if they are used for fraudulent purposes. In conclusion, the parenteral administration of dexamethasone or ketoprofen 48 h after the PPDs administration can significantly reduce the increase in SFT (mm) and subsequently the number of positive reactors to SIT test.

Effect of heat-inactivated Mycobacterium avium subspecies paratuberculosis (MAP) vaccine on the lesions and immunopathology developed in target tissues of naturally MAP-infected goats.

Paratuberculosis (PTB) is a disease caused by Mycobacterium avium subspecies paratuberculosis (MAP), which affects a broad range of hosts, including domestic and wild animals. PTB is a chronic granulomatous enteritis and lymphadenitis that compromises animal welfare and causes economic losses. The objective of this study was to evaluate the effect of a commercial heat-inactivated MAP vaccine on lesions and immunopathology developed in the target tissues of goats naturally infected with MAP. Lesions compatible with PTB in the intestine and regional lymph nodes (LNs), as well as local immune response to MAP, were evaluated and compared in Gudair®-vaccinated (n = 14) and unvaccinated (n = 11) goats from a MAP-infected farm. The percentage of animals with multifocal granulomatous lesions in the jejunal (p = 0.05) and ileocecal (p = 0.02) LNs was higher in unvaccinated animals, while a lesion score reduction of 50% was found in the LNs of vaccinated animals. Unvaccinated animals showed increased numbers and wider distribution of macrophages (MΦs, CD68 +) in histiocytic infiltrate (p = 0.0003), associated with increased numbers of mycobacteria. Increased inducible nitric oxide synthase (iNOS) expression was also reported in these animals, while M2 MΦs (CD163 +) were scarce in both groups. Vaccinated animals showed an increase in CD3 + lymphocytes, although differences in interferon gamma (IFNγ) were negligible. These results support the hypothesis that heat-inactivated MAP vaccination could reduce the severity of PTB lesions and mycobacterial load in target tissues in vaccinated adult goats.

Effect of the Inoculation Site of Bovine and Avian Purified Protein Derivatives (PPDs) on the Performance of the Intradermal Tuberculin Test in Goats From Tuberculosis-Free and Infected Herds.

The single and comparative intradermal tuberculin (SIT and CIT) tests are used for the ante-mortem diagnosis of caprine tuberculosis (TB). The tuberculin injection site has been associated with a different performance of the test in cattle. In contrast to that required in cattle in Europe (cervical injection), it can be carried out in the scapular region in goats. Nevertheless, there are no previous data concerning the effect of the injection site on the performance of the test in goats. The aim of the present study was to evaluate the effect of two different inoculation sites (cervical and scapular) on the performance of the SIT/CIT tests. This was done by intradermally inoculating 309 goats from two infected herds and one TB-free herd with both avian and bovine PPDs in the mid-cervical and scapular regions. None of the animals from the TB-free herd had positive reactions, and the number of reactors was not significantly higher, regardless of the inoculation site, in the high and low prevalence herds. However, significantly higher increases in skin fold thickness were observed on the cervical site when compared to the scapular site after the avian and bovine PPD inoculations in the TB-free herd (p < 0.001) and after the bovine PPD injection in the high prevalence herd (p = 0.003). The presence of clinical signs was also more evident on the cervical site when using avian and bovine PPDs in the high prevalence herd (p < 0.01). In contrast, increases in higher skin fold thickness were observed on the scapular site when compared to the cervical site after the bovine and avian PPD inoculations were employed in the low prevalence herd (p < 0.01). These results suggest that the cervical injection of PPDs may improve the sensitivity of the intradermal tuberculin test in high TB prevalence caprine herds, mainly owing to the increased presence of local clinical signs and a better performance of the CIT test. Moreover, specificity was not affected when using standard interpretations, although further analyses in a great number of herds are required in order to confirm these findings.

Evaluation of P22 ELISA for the Detection of Mycobacterium bovis-Specific Antibody in the Oral Fluid of Goats.

The ante-mortem diagnosis of tuberculosis (TB) in ruminants is based mainly on the intradermal tuberculin test and the IFN-γ assay. Antibody (Ab)-based tests have emerged as potential tools for the detection of TB infected animals using serum, plasma, or even milk samples. Oral fluids have also been evaluated as alternative samples with which to detect specific Abs against Mycobacterium bovis in pigs or wild boars, but not in ruminants. The objective of this study was, therefore, to evaluate the performance of an in house-ELISA for TB diagnosis (P22 ELISA) in goats as an experimental model for the diagnosis of TB using oral fluid samples. Oral fluid samples from 64 goats from a TB-infected herd (n = 197) and all the animals from a TB-free herd (n = 113) were analyzed using the P22 ELISA. The estimated sensitivity (Se) and specificity (Sp) were 34.4% (95% CI: 22.4-45.6) and 100% (95% CI: 97.4-100), respectively. The optimal cut-off point was set at 100% according to the ROC analysis. Those animals with a higher level of Abs in their oral fluid attained a higher lesion score (p = 0.018). In fact, when taking into account only the setting of the animals with severe lesions (n = 16), the ELISA showed a Se of 75% (95% CI: 53.7-96.2). Results of the present study suggest that the P22 ELISA is highly specific but has a limited value detecting infected animals in oral fluid samples. Nevertheless, its performance is significantly higher in the presence of severe lesions.

Exacerbados. Identidades académicas y la transformación de la educación superior chilena / Exacerbated. Academic Identities and the Transformation of Chilean Higher Education

La diversificación de fuentes de financiamiento, instalación de la cultura de accountability y medidas para maximizar la eficacia de diferentes procesos académicos son expresiones de una educación superior en transformación, que precisa de la estratégica reorganización de su fuerza laboral académica. La gestión universitaria ha concretado estos cambios en nuevas formas de concebir, medir e incentivar el trabajo académico. La nueva gestión dispone al cuerpo académico a la construcción y apropiación de nuevasidentidades laborales; no obstante, éstas no son asumidas por los/as trabajadores/as sin conflicto. A partir del análisis de 40 entrevistas a académicos/as, se reportan los hallazgos en 3 categorías, a saber: narrativas identitarias del académico/a crítico/a, narrativas identitarias del académico/a solitario/a y narrativas identitarias del académico/a prestigioso/a. Como discusión se expone como estas narrativas converen y exacerban, dadas las transformaciones de la educación superior.(AU)

The diversification of funding sources, the installation of the accountability culture and measures to maximize the effectiveness of different academic processes are expressions of higher education in transformation, which requires the strategic reorganization of its academic workforce. University management has materialized these changes in new ways of conceiving, measuring and encouraging academic work. University management has materialized these changes in new ways of conceiving, measuring and encouraging academic work. Based on the analysis of 40 interviews with academics, the present paper reports the findings in 3 categories, namely: identity narratives of the critical academic, identity narratives of the solitary academic and identity narratives of the prestigious academic.(AU)

Hypervitaminosis D has no positive effects on goat tuberculosis and may cause chronic renal lesions.

BACKGROUND: There is evidence for a link between vitamin D deficiency and active tuberculosis (TB). In human beings, several trials have evaluated the role of vitamin D supplementation in TB treatment with conflicting results. However, the role of vitamin D supplementation in animal TB control has received less attention. The authors evaluated the benefit of vitamin D supplementation for preventing mycobacterial infection or reducing TB lesions (TBL) in a controlled trial with goats naturally exposed to Mycobacterium caprae. METHODS: Two groups of goats, a vitamin D-supplemented group and a non-supplemented control group, were housed for 10 months in direct contact with M caprae-infected adult goats. Upon contact with the infected adult goats, all animals were TB-tested every two months. RESULTS: No experimental evidence of a protective effect of vitamin D supplementation based on M caprae culture prevalence, TBL prevalence, median TBL score or the proportion of single versus multiple organs presenting TBL was observed. CONCLUSION: The results indicate that, in the conditions used in this study, vitamin D supplementation in goats does not reduce TB infection risk nor the diffusion and severity of TBL. In addition, vitamin D-supplemented goats presented hyperphosphataemia and renal injury with calcifications suggestive of vitamin D intoxication.

Evaluation of the immunogenicity and efficacy of BCG and MTBVAC vaccines using a natural transmission model of tuberculosis.

Effective vaccines against tuberculosis (TB) are needed in order to prevent TB transmission in human and animal populations. Evaluation of TB vaccines may be facilitated by using reliable animal models that mimic host pathophysiology and natural transmission of the disease as closely as possible. In this study, we evaluated the immunogenicity and efficacy of two attenuated vaccines, BCG and MTBVAC, after each was given to 17 goats (2 months old) and then exposed for 9 months to goats infected with M. caprae. In general, MTBVAC-vaccinated goats showed higher interferon-gamma release than BCG vaccinated goats in response to bovine protein purified derivative and ESAT-6/CFP-10 antigens and the response was significantly higher than that observed in the control group until challenge. All animals showed lesions consistent with TB at the end of the study. Goats that received either vaccine showed significantly lower scores for pulmonary lymph nodes and total lesions than unvaccinated controls. Both MTBVAC and BCG vaccines proved to be immunogenic and effective in reducing severity of TB pathology caused by M. caprae. Our model system of natural TB transmission may be useful for evaluating and optimizing vaccines.

Response of goats to intramuscular vaccination with heat-killed Mycobacterium bovis and natural challenge.

Caprine TB causes chronic disease with severe economic and health consequences. We assessed the effect of intramuscularly administered heat-inactivated Mycobacterium bovis (M. bovis) on 20 kid goats (10 vaccinated, 10 controls), naturally exposed to M. caprae through close contact with infected goats. At necropsy, visible TB-compatible lesions were recorded in all animals with the exception of 1 control and 2 vaccinated goats. The median of the total lesion score was 9 (IQR 3-13.5) and 5 (IQR 3-6.75) in control and vaccinated goats, respectively (median lesion reduction 44.4%, p = 0.224). The lung lesions of the vaccinated goats were restricted to the caudal lobes, while 6 controls had additional lung lobes affected (p = 0.01). The median lung lesion score reduction in vaccinated goats was 100%; however, this reduction was not significant (p = 0.124), possibly due to the low sample size. Regarding the abdomen, only one vaccinated goat presented visible lesions compared to three goats in the control group. The results provide further evidence of the potential of heat-inactivated M. bovis for controlling TB in different host species, including ruminants.

Development and Evaluation of a Serological Assay for the Diagnosis of Tuberculosis in Alpacas and Llamas.

South American camelids are susceptible to tuberculosis, caused mainly by Mycobacterium bovis and M. microti. Despite the tuberculin skin test being the official test for tuberculosis, it has a very low sensitivity in these species (14-20%). Serological tests present the advantages of being rapid, easy to perform and facilitate analysis of large numbers of samples in a short period of time. Novel antigen discovery and evaluation would provide enhanced detection of specific antibodies against members of M. tuberculosis complex. Here, we describe the development and evaluation of an ELISA-type immunoassays to use in the diagnosis of tuberculosis in llamas and alpacas based on P22, a multiprotein complex obtained by affinity chromatography from bovine Purified Protein Derivative (bPPD), that showed high sensitivity and specificity in mice, cattle and goats. This work was performed in two stages. First, a preliminary panel of samples collected from tuberculosis-free (n = 396) and M. bovis-infected herds (n = 56) was assayed, obtaining high specificity (100%) and sensitivity ranging from 63 to 96%. Subsequently, the use of the serological assay was tested using samples from two herds suffering from clinical M. bovis (n = 88) and M. microti (n = 25) infection to evaluate the ability of the ELISA to detect infected animals. 11 out of 88 alpacas were positive to the ELISA in a M. bovis outbreak and 7 out of 25 in a M. microti outbreak. The P22 ELISA potentially provides a sensitive and specific platform for improved tuberculosis surveillance in camelids.

Temporal analysis of the interference caused by paratuberculosis vaccination on the tuberculosis diagnostic tests in goats.

Vaccination against paratuberculosis (PTB) in goats is a cost-effective control strategy, and is also effective as regards preventing the onset of clinical cases. However, it causes interference in the diagnostic tests used in the control of tuberculosis (TB). A group of 99 goats from a herd with no history of TB or PTB infection was vaccinated against PTB at seven months of age. They then underwent consecutive intradermal tests [single (SIT) and comparative (CIT) intradermal tuberculin tests), interferon-gamma release assays (IGRA) and two serological tests (p22_CE and DR-ELISA) every three months, until the interference disappeared. When using the SIT test, a variable number of positive reactors were observed at 3 months (T3; 32.3%, 95% CI 23.9-42.1), 6 months (T6; 11.5%, 95% CI 6.5-19.4), 9 months (T9; 6.4%, 95% CI 3.0-13.2) and 12 months (T12; 0%, 95% CI 0-4.0) post-vaccination. In contrast, the CIT test had a specificity (Sp) of 100% (95%, CI 96.0-100, regardless of the time post-vaccination. The IGRA also obtained high Sp values throughout the study period. No significant interference in the serological tests was recorded at T3 [p22_CE, Sp = 96% (95% CI 90.1-98.4) and DR-ELISA, Sp = 98% (95% CI 92.9-99.4)], although an increase in antibody titers was observed in the following herd testing events. In conclusion, the use of the SIT test causes the onset of false-positive reactors if applied before 12 months post-vaccination in a TB-free/PTB-vaccinated herd. Nevertheless, the CIT test and IGRA obtained high Sp values under these epidemiological circumstances. The serological tests were also highly specific in the case of PTB-vaccinated goats, although their Sp decreased significantly after several intradermal tests.

The use of serological tests in combination with the intradermal tuberculin test maximizes the detection of tuberculosis infected goats.

The diagnosis of tuberculosis (TB) in goats is based mainly on the single and comparative intradermal tuberculin (SIT and CIT) tests and, exceptionally, on the interferon-gamma (IFN-γ) assay, however they are not perfect in terms of sensitivity and specificity. Nevertheless, various serological assays that provide a potential cost-effective approach for the control of TB are also available or under development, and a variety of results have been reported regarding the ability of these tests to detect infected animals, particularly in the early stages of infection. In the present study, SIT/CIT and IFN-γ tests and three different serological assays were evaluated during two consecutive herd testing events in a recently infected caprine herd (n = 447) with a high prevalence of infection in order to evaluate their performance and provide field data with which to improve the TB control programs in this species. The proportion of infected animals that tested positive among all the infected goats (T+/I+ value) in the last herd testing event ranged from 26.2% (IC95%; 19.3-34.5) to 85.7% (IC95%; 78.5-90.7) using cell-based diagnostic tests. The SIT/SCIT tests detected more infected goats than the IFN-γ test, regardless of the interpretation criteria. The T+/I+ value of serology was 83.2 (IC95%; 75.2-89), although it increased significantly (P < 0.05) when using samples collected 15 days after the intradermal test (100%, IC95%; 97-100). In general, a parallel interpretation of intradermal tests with serology maximized the detection of infected goats. These results demonstrate that serological tests are valuable diagnostic tools to maximize the detection of TB infected goats, even in recent outbreaks, accelerating the eradication process.

Proteomic characterisation of bovine and avian purified protein derivatives and identification of specific antigens for serodiagnosis of bovine tuberculosis.

BACKGROUND: Bovine purified protein derivative (bPPD) and avian purified protein derivative (aPPD) are widely used for bovine tuberculosis diagnosis. However, little is known about their qualitative and quantitative characteristics, which makes their standardisation difficult. In addition, bPPD can give false-positive tuberculosis results because of sequence homology between Mycobacterium bovis (M. bovis) and M. avium proteins. Thus, the objective of this study was to carry out a proteomic characterisation of bPPD, aPPD and an immunopurified subcomplex from bPPD called P22 in order to identify proteins contributing to cross-reactivity among these three products in tuberculosis diagnosis. METHODS: Trypsin digests of bPPD, aPPD and P22 were analysed by nanoscale liquid chromatography-electrospray ionization tandem mass spectrometry. Mice were immunised with bPPD or aPPD, and their serum was tested by indirect ELISA for reactivity against these preparations as well as against P22. RESULTS: A total of 456 proteins were identified in bPPD, 1019 in aPPD and 118 in P22; 146 of these proteins were shared by bPPD and aPPD, and 43 were present in all three preparations. Candidate proteins that may cause cross-reactivity between bPPD and aPPD were identified based on protein abundance and antigenic propensity. Serum reactivity experiments indicated that P22 may provide greater specificity than bPPD with similar sensitivity for ELISA-type detection of antibodies against M. tuberculosis complex. CONCLUSION: The subpreparation from bPPD called P22 may be an alternative to bPPD for serodiagnosis of bovine tuberculosis, since it shares fewer proteins with aPPD than bPPD does, reducing risk of cross-reactivity with anti-M. avium antibodies.

Oral Vaccination with Heat-Inactivated Mycobacterium bovis Does Not Interfere with the Antemortem Diagnostic Techniques for Tuberculosis in Goats.

Vaccination against tuberculosis (TB) is prohibited in cattle or other species subjected to specific TB eradication campaigns, due to the interference that it may cause with the official diagnostic tests. However, immunization with a heat-inactivated (HI) Mycobacterium bovis vaccine via the oral route has been suggested to overcome this issue. In this study, the main goal was to assess the interference of the HI vaccine by different routes of administration using a previous vaccination and re-vaccination (boosting) protocol. TB-free kid goats were divided into three groups: oral (n = 16), intramuscular (IM; n = 16), and control (n = 16). Results showed that there was a significant difference in the percentage of animals positive to the single intradermal test (SIT) and blood based interferon-gamma release assay (IGRA) caused by vaccination when performed in the IM group compared to the oral group (p < 0.001). Nevertheless, no positivity to the SIT or IGRA test was observed in orally vaccinated goats regardless of the different interpretation criteria applied. None of the groups presented positive antibody titers using an in-house ELISA and samples collected 2 months after the boost. These results suggest the potential usefulness of the HI vaccine by the oral route in goats to minimize the interference on diagnostic tests (skin and IGRA tests) and reducing the necessity of defined antigens to replace the traditional purified protein derivatives for diagnosis. Finally, the results pave the way to future efficacy studies in goats using different routes of HI vaccination.

Tensiones en la construcción identitaria individualizada en el trabajo flexible / Tensions in individual identity construction in flexible working

El presente trabajo se propone una reflexión acerca de las tensiones y contradicciones de los procesos de construcción identitaria en el trabajo flexible, a partir de los resultados de una investigación en empresas chilenas. El análisis propone la existencia de dinámicas caracterizadas por la tensión entre los elementos heredados de la trayectoria y los aspectos deseados a nivel identitario, así como de las distancias y contradicciones existentes entre la dimensión individual y la colectiva de la construcción identitaria.

The article proposed a reflection on the tensions and contradictions of identity construction processes in flexible work, within the results of a research in some Chilean companies. The analysis suggests the existence of dynamics characterized by a tension between inherited elements from the trajectory and desired aspects in an identity level, as well as distances and contradictions between individual and collective dimensions of identity construction.