Cellular and humoral immune responsiveness to inactivated Leptospira interrogans in dogs vaccinated with a tetravalent Leptospira vaccine

Vaccination is commonly used to protect dogs against leptospirosis, however, memory immune responses induced by canine Leptospira vaccines have not been studied. In the present study, antibody and T cell mediated responses were assessed in dogs before and 2 weeks after annual revaccination with a commercial tetravalent Leptospira vaccine containing serogroups Canicola and Australis. Vaccination significantly increased average log 2 IgG titers from 6.50 to 8.41 in year 1, from 5.99 to 7.32 in year 2, from 5.32 to 8.32 in year 3 and from 5.32 to 7.82 in year 4. The CXCL-10 levels, induced by in vitro stimulation of PBMC with Canicola and Australis, respectively, significantly increased from 1039.05 pg/ml and 1037.38 pg/ml before vaccination to 2547.73 pg/ml and 2730.38 pg/ml after vaccination. IFN-γ levels increased from 85.60 pg/ml and 178.13 pg/ml before vaccination to 538.62 pg/ml and 210.97 pg/ml after vaccination. The percentage of proliferating CD4 + T cells in response to respective Leptospira strains significantly increased from 1.43 % and 1.25 % before vaccination to 24.11 % and 14.64 % after vaccination. Similar responses were also found in the CD8 + T cell subset. Vaccination also significantly enhanced the percentages of central memory CD4 + T cells from 12 % to 26.97 % and 27.65 %, central memory CD8 + T cells from 3 % to 9.47 % and 7.55 %, and effector CD8 + T cells from 3 % to 7.6 % and 6.42 %, as defined by the expression of CD45RA and CD62L, following stimulation with Canicola and Australis, respectively. Lastly, enhanced expression of the activation marker CD25 on T cells after vaccination was found. Together, our results show that next to IgG responses, also T cell responses are induced in dogs upon annual revaccination with a tetravalent Leptospira vaccine, potentially contributing to protection

Cellular and humoral immune responsiveness to inactivated Leptospira interrogans in dogs vaccinated with a tetravalent Leptospira vaccine

Vaccination is commonly used to protect dogs against leptospirosis, however, memory immune responses induced by canine Leptospira vaccines have not been studied. In the present study, antibody and T cell mediated responses were assessed in dogs before and 2 weeks after annual revaccination with a commercial tetravalent Leptospira vaccine containing serogroups Canicola and Australis. Vaccination significantly increased average log 2 IgG titers from 6.50 to 8.41 in year 1, from 5.99 to 7.32 in year 2, from 5.32 to 8.32 in year 3 and from 5.32 to 7.82 in year 4. The CXCL-10 levels, induced by in vitro stimulation of PBMC with Canicola and Australis, respectively, significantly increased from 1039.05 pg/ml and 1037.38 pg/ml before vaccination to 2547.73 pg/ml and 2730.38 pg/ml after vaccination. IFN-γ levels increased from 85.60 pg/ml and 178.13 pg/ml before vaccination to 538.62 pg/ml and 210.97 pg/ml after vaccination. The percentage of proliferating CD4 + T cells in response to respective Leptospira strains significantly increased from 1.43 % and 1.25 % before vaccination to 24.11 % and 14.64 % after vaccination. Similar responses were also found in the CD8 + T cell subset. Vaccination also significantly enhanced the percentages of central memory CD4 + T cells from 12 % to 26.97 % and 27.65 %, central memory CD8 + T cells from 3 % to 9.47 % and 7.55 %, and effector CD8 + T cells from 3 % to 7.6 % and 6.42 %, as defined by the expression of CD45RA and CD62L, following stimulation with Canicola and Australis, respectively. Lastly, enhanced expression of the activation marker CD25 on T cells after vaccination was found. Together, our results show that next to IgG responses, also T cell responses are induced in dogs upon annual revaccination with a tetravalent Leptospira vaccine, potentially contributing to protection

The value of nonoperative versus operative treatment of frail institutionalized elderly patients with a proximal femoral fracture in the shade of life (FRAIL-HIP); protocol for a multicenter observational cohort study

Background: Proximal femoral fractures are strongly associated with morbidity and mortality in elderly patients. Mortality is highest among frail institutionalized elderly with both physical and cognitive comorbidities who consequently have a limited life expectancy. Evidence based guidelines on whether or not to operate on these patients in the case of a proximal femoral fracture are lacking. Practice variation occurs, and it remains unknown if nonoperative treatment would result in at least the same quality of life as operative treatment. This study aims to determine the effect of nonoperative management versus operative management of proximal femoral fractures in a selected group of frail institutionalized elderly on the quality of life, level of pain, rate of complications, time to death, satisfaction of the patient (or proxy) and the caregiver with the management strategy, and health care consumption. Methods: This is a multicenter, observational cohort study. Frail institutionalized elderly (70 years or older with a body mass index < 18.5, a Functional Ambulation Category of 2 or lower pre-trauma, or an American Society of Anesthesiologists score of 4 or 5), who sustained a proximal femoral fracture are eligible to participate. Patients with a pathological or periprosthetic fractures and known metastatic oncological disease will be excluded. Treatment decision will be reached following a structured shared decision process. The primary outcome is quality of life (Euro-QoL; EQ-5D-5 L). Secondary outcome measures are quality of life measured with the QUALIDEM, pain level (PACSLAC), pain medication use, treatment satisfaction of patient (or proxy) and caregivers, quality of dying (QODD), time to death, and direct medical costs. A cost-utility and cost-effectiveness analysis will be done, using the EQ-5D utility score and QUALIDEM score, respectively. Non-inferiority of nonoperative treatment is assumed with a limit of 0.15 on the EQ-5D score. Data will be acquired at 7, 14, and 30 days and at 3 and 6 months after trauma. Discussion: The results of this study will provide insight into the true value of nonoperative treatment of proximal femoral fractures in frail elderly with a limited life expectancy. The results may be used for updating (inter)national treatment guidelines. Trial registration: The study is registered at the Netherlands Trial Register (NTR7245; date 10-06-2018)