Humoral and cell-mediated immune responses after a booster dose of HBV vaccine in HIV-infected children, adolescents and young adults

OBJECTIVE: HBV vaccine induces protective antibodies only in 23-56% of HIV-infected children. The aim of our study is to evaluate the immunologic effects of a booster dose of HBV vaccine in HIV-infected youth. DESIGN: 53 young HIV-infected patients in whom HBV vaccination did not elicit protective Ab titers were enrolled. All patients were on ART with optimal immunological and viral response. METHOD: All patients received a booster dose of HBV vaccine (HBVAXPRO 10 \u3bcg i.m.). HBV-specific Ab titer, viral load and CD4+ T cells were measured at baseline (T0), T1, T6 and T12 months. In a subgroup of 16 patients HBV-specific cell mediated immune responses were evaluated at baseline, at T1 and T6. RESULTS: The booster dose induced seroconversion in 51% of patients at T1, 57% at T6, and49% at T12; seroconversion rate was significantly correlated with CD4+T cells at T0 and to the CD4 nadir. The booster dose induced HBV-specific cell mediated immunity at T6 mainly in Responders (Rs): Effector Memory CD8+T cells, HBV-specific TNF\u3b1-, IFN\u3b3-, granzyme secreting CD8+ T cells and IL2-secreting CD4+ T cells were significantly increased in Rs compared to T0. In Non Responders (NRs), HBV-specific IL2-secreting CD4+ T cells, Central and Effector Memory CD8+ T cells were the only parameters modified at T6. CONCLUSIONS: Seroconversion induced by a booster dose of vaccine correlates with the development of T cell immunological memory in HIV-infected patients who did not respond to the standard immunization. Alternate immunization schedules need to be considered in NRs

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Ceremonial plant consumption at Middle Bronze Age Büklükale, Kırıkkale Province, central Turkey

A shaft-like room at the Middle Bronze Age site of Büklükale in central Turkey preserved a rich archaeobotanical assemblage of charred and mineralised plant remains, dominated by fruits, spices and nuts mixed with probable bread and wood charcoals. The remains were recovered in association with numerous ceramic vessels, jewellery and exotic artefacts. We combine identification and analysis of the seeds and wood charcoals contained in this deposit with studies of Old Assyrian and Hittite textual records to investigate the circumstances of the assemblage’s formation and its significance for further understanding trade and plant consumption in Bronze Age Anatolia. We present the earliest archaeobotanical example in the region of rare and exotic plant species being consumed in the context of one or more social gatherings, including those possibly linked to ceremonial or ritual events. This offers new insights into the role of plants in the economic and social life of the southwest Asian Bronze Age, as well as the role of commensality and feasting in early states

Immunological response after a booster dose of HBV vaccine in HIV-infected youth

Background: Three doses of vaccine against HBV induce the production of protective antibody (Ab) levels (>10 IU/mL) in 95-100 % of healthy children but in only 23-56% of HIV-infected children. Ab titer elicited by vaccination decreases over time in both populations with a faster slope observed in HIV+. This decline protection against HBV is known to last almost three decades after vaccination in immunocompetent children, these data are limited in HIV+ children Methods: 53 HIV+ patients (aged 8-25 years old) in whom HBV vaccination according the Italian schedule did not elicit the generation of protective Ab titers were enrolled in the study at Paediatric Infectious Diseases Unit, L. Sacco Hospital, University of Milan. All patients had undergone ART for at least 1 year; HIV viral load was undetectable in all of them, median CD4+ count 718 mm3. All patients received a booster dose of HBV vaccine (HBVAXPRO 10 micrograms i.m.). HBV-specific Ab titer, viral load and CD4 + were measured in all subjects at baseline (T0), at 1 (T1), 6 (T6) and 12 (T12) months after the booster dose. In a subgroup of 16 patients HBV-specific cell mediated immune (CMI) responses were evaluated at baseline and at T6. Results: The booster HBV vaccine dose resulted in a seroconversion rate (anti-HBs 65 10 IU/mL) in 51% of patients at T1, 57% at T6 and 49% at T12; seroconversion rate was significantly correlated with CD4+T lymphocyte counts at T0 and to CD4 nadir (p10 IU/mL) and 5 non-responders (HBsAb <10 IU/mL). Upregulation of HBV-specific CMI compared to baseline values was observed at T6 in responders alone. Memory (p= 0.007), Effector Memory (p= 0.003), TNF\uf061- (p= 0.041), IFN\uf067- (p= 0.004), and granzyme-secreting CD8+ T cells (p= 0.003), Central Memory (p= 0.005) and IL2-secreting CD4+ T cells (p= 0.015) were significantly increased in responders compared to baseline values. Activated CD8+CD38+CD45RO+ T cells (p= 0.004) were significantly reduced as well at T6 in these individuals. No significant differences were observed when T0 and T6 data were compared in non responders. Conclusions: In HIV+ patients no responding to the standard HBV immunization protocol, seroconversion induced by a booster dose of vaccine (Ab titers <10 IU/mL) correlates with the development of T cell immunological memory. Alternate immunization schedules should be designed for those individuals who don't respond even to a booster dose of vaccin

Saliva molecular testing for sars-cov-2 surveillance in two italian primary schools

Background: No evidence has so far proven a significant role of schools in SARS-CoV-2 transmission, while the negative effects of their closure on children and adolescents are well documented. Surveillance, by means of frequent students and staff testing, has been advocated in order to implement school safety. Our aim was to report the results of a school surveillance program for the early detection of SARS-CoV-2 infection in pre- and asymptomatic subjects, by means of molecular salivary testing (MST). Methods: School surveillance in two schools in Milan, Italy, was carried out for six weeks. Each participant received a saliva collection kit, to be self-performed. Results: 401 students and 12 teachers were enrolled, and 5 positive children in 5 different classes were observed. All the cases were asymptomatic. Their nasopharyngeal swab was positive on the same day in four cases, while in one case it resulted negative on the same day and positive 3 days later. In one positive case, the whole family was set under surveillance. The positive child did not develop symptoms and no family member was infected. Conclusions: MST might represent an efficient way to actively survey communities in order to detect asymptomatic cases, thus limiting SARS-CoV-2 transmission

Unknown cytomegalovirus serostatus in primary immunodeficiency disorders: A new category of transplant recipients.

BackgroundCytomegalovirus (CMV) serostatus of recipient (R) and donor (D) influences hematopoietic stem cell transplant (HSCT) outcome. However, it is not a reliable indicator of CMV infection in primary immunodeficiency disorder (PIDD) recipients who are unable to make adequate antigen-specific immunoglobulin (Ig) or who receive intravenous Ig (IVIg) prior to testing.ObjectiveSince no data exist on PIDD with unknown CMV serostatus, we aimed to evaluate the relationship between pre-HSCT recipient and donor serostatus and incidence of CMV infection in recipients with unknown serostatus.MethodsA retrospective analysis of all pediatric PIDD HSCTs (2007-2018) was performed at University of California San Francisco. Recipients were separated into categories based on pre-transplant serostatus: 1) seropositive (R(+)), 2) seronegative (R(-)), and 3) unknown serostatus (R(x)). Patients with pre-HSCT active CMV viremia were excluded.ResultsA total of 90 patients were included, 69% male. The overall incidence of CMV infection was 20%, but varied in R(+), R(-), and R(x) at 80%, 0%, and 14%, (P-value&nbsp;=&nbsp;.0001). Similarly, 5-year survival differed among groups, 60% R(+), 100% R(-), and 90% of R(x) (P-value&nbsp;=&nbsp;.0045). There was no difference in CMV reactivation by donor serostatus (P-value&nbsp;=&nbsp;.29), however, faster time to clearance of CMV was observed for R(x)/D(+) group (median 9.5&nbsp;days (IQR 2.5-18), P-value&nbsp;=&nbsp;.024).ConclusionWe identify a novel group of recipients, R(x), with an intermediate level of survival and CMV incidence post-HSCT, when compared to seropositive and seronegative recipients. No evidence of CMV transmission from D(+) in R(-) and R(x) was observed. We believe R(x) should be considered as a separate category in future studies to better delineate recipient risk status

Impact of Genetic Diagnosis on the Outcome of Hematopoietic Stem Cell Transplant in Primary Immunodeficiency Disorders

Abstract To evaluate the relationship between knowledge of genetic diagnosis before HSCT and outcome, we reviewed all HSCTs for primary immune deficiencies (PID) performed at UCSF from 2007 through 2018. SCID, a distinct entity identified since 2010 in California by newborn screening and treated early, was considered separately. The underlying genetic condition was known at the time of HSCT in 85% of cases. Graft failure was less frequent in patients with a genetic diagnosis (19% with a genetic diagnosis versus 47% without, p=0.020). Furthermore, event-free survival and overall survival (OS) at 5 years were better for those with a genetic diagnosis (78% with versus 44% without, p=0.006; and 93% versus 60% without, p=0.0002, respectively). OS at 5 years was superior for known-genotype patients with both SCID (p=0.010) and non-SCID PID (p=0.010). There was no difference in OS between HSCT done in 2007-2010 compared to more recently (p=0.19). These data suggest that outcomes of HSCT for PID with known genotype may reflect specific experience and literature, or that a substantial proportion of patients with PID of undetermined genotype may have had underlying conditions for which HSCT may carry greater risk. The higher rate of graft failure in PID with unknown genotype may be in part explained by insufficient conditioning, which in turn could be dictated by compromised organ function in patients undergoing HSCT late in the course. Widespread availability of PID gene sequencing as standard care can provide genetic diagnoses for most patients with PID prior to HSCT, permitting optimization of transplant approach.</jats:p

Impact of Genetic Diagnosis on the Outcome of Hematopoietic Stem Cell Transplant in Primary Immunodeficiency Disorders

To evaluate the relationship between knowledge of genetic diagnosis before HSCT and outcome, we reviewed all HSCTs for primary immune deficiencies (PID) performed at UCSF from 2007 through 2018. SCID, a distinct entity identified since 2010 in California by newborn screening and treated early, was considered separately. The underlying genetic condition was known at the time of HSCT in 85% of cases. Graft failure was less frequent in patients with a genetic diagnosis (19% with a genetic diagnosis versus 47% without, p = 0.020). Furthermore, event-free survival and overall survival (OS) at 5&nbsp;years were better for those with a genetic diagnosis (78% with versus 44% without, p = 0.006; and 93% versus 60% without, p = 0.0002, respectively). OS at 5&nbsp;years was superior for known-genotype patients with both SCID (p = 0.010) and non-SCID PID (p = 0.010). There was no difference in OS between HSCT done in 2007-2010 compared to more recently (p = 0.19). These data suggest that outcomes of HSCT for PID with known genotype may reflect specific experience and literature, or that a substantial proportion of patients with PID of undetermined genotype may have had underlying conditions for which HSCT may carry greater risk. The higher rate of graft failure in PID with unknown genotype may be in part explained by insufficient conditioning, which in turn could be dictated by compromised organ function in patients undergoing HSCT late in the course. Widespread availability of PID gene sequencing as standard care can provide genetic diagnoses for most patients with PID prior to HSCT, permitting optimization of transplant approach