Cellular and humoral immunogenicity of the mRNA-1273 SARS-CoV-2 vaccine in patients with hematologic malignancies.

Recent studies have shown a suboptimal humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in patients diagnosed with hematologic malignancies; however, data about cellular immunogenicity are scarce. The aim of this study was to evaluate both the humoral and cellular immunogenicity 1 month after the second dose of the mRNA-1273 vaccine. Antibody titers were measured by using the Elecsys and LIAISON anti-SARS-CoV-2 S assays, and T-cell response was assessed by using interferon-γ release immunoassay technology. Overall, 76.3% (184 of 241) of patients developed humoral immunity, and the cellular response rate was 79% (184 of 233). Hypogammaglobulinemia, lymphopenia, active hematologic treatment, and anti-CD20 therapy during the previous 6 months were associated with an inferior humoral response. Conversely, age >65 years, active disease, lymphopenia, and immunosuppressive treatment of graft-versus-host disease (GVHD) were associated with an impaired cellular response. A significant dissociation between the humoral and cellular responses was observed in patients treated with anti-CD20 therapy (the humoral response was 17.5%, whereas the cellular response was 71.1%). In these patients, B-cell aplasia was confirmed while T-cell counts were preserved. In contrast, humoral response was observed in 77.3% of patients undergoing immunosuppressive treatment of GVHD, whereas only 52.4% had a cellular response. The cellular and humoral responses to the SARS-CoV-2 mRNA-1273 vaccine in patients with hematologic malignancies are highly influenced by the presence of treatments such as anti-CD20 therapy and immunosuppressive agents. This observation has implications for the further management of these patients.

Effect of Recombinant Zoster Vaccine on Incidence of Herpes Zoster After Autologous Stem Cell Transplantation: A Randomized Clinical Trial.

Importance: Herpes zoster, a frequent complication following autologous hematopoietic stem cell transplantation (HSCT), is associated with significant morbidity. A nonlive adjuvanted recombinant zoster vaccine has been developed to prevent posttransplantation zoster. Objective: To assess the efficacy and adverse event profile of the recombinant zoster vaccine in immunocompromised autologous HSCT recipients. Design, Setting, and Participants: Phase 3, randomized, observer-blinded study conducted in 167 centers in 28 countries between July 13, 2012, and February 1, 2017, among 1846 patients aged 18 years or older who had undergone recent autologous HSCT. Interventions: Participants were randomized to receive 2 doses of either recombinant zoster vaccine (n = 922) or placebo (n = 924) administered into the deltoid muscle; the first dose was given 50 to 70 days after transplantation and the second dose 1 to 2 months thereafter. Main Outcomes and Measures: The primary end point was occurrence of confirmed herpes zoster cases. Results: Among 1846 autologous HSCT recipients (mean age, 55 years; 688 [37%] women) who received 1 vaccine or placebo dose, 1735 (94%) received a second dose and 1366 (74%) completed the study. During the 21-month median follow-up, at least 1 herpes zoster episode was confirmed in 49 vaccine and 135 placebo recipients (incidence, 30 and 94 per 1000 person-years, respectively), an incidence rate ratio (IRR) of 0.32 (95% CI, 0.22-0.44; P < .001), equivalent to 68.2% vaccine efficacy. Of 8 secondary end points, 3 showed significant reductions in incidence of postherpetic neuralgia (vaccine, n=1; placebo, n=9; IRR, 0.1; 95% CI, 0.00-0.78; P = .02) and of other prespecified herpes zoster-related complications (vaccine, n=3; placebo, n=13; IRR, 0.22; 95% CI, 0.04-0.81; P = .02) and in duration of severe worst herpes zoster-associated pain (vaccine, 892.0 days; placebo, 6275.0 days; hazard ratio, 0.62; 95% CI, 0.42-0.89; P = .01). Five secondary objectives were descriptive. Injection site reactions were recorded in 86% of vaccine and 10% of placebo recipients, of which pain was the most common, occurring in 84% of vaccine recipients (grade 3: 11%). Unsolicited and serious adverse events, potentially immune-mediated diseases, and underlying disease relapses were similar between groups at all time points. Conclusions and Relevance: Among adults who had undergone autologous HSCT, a 2-dose course of recombinant zoster vaccine compared with placebo significantly reduced the incidence of herpes zoster over a median follow-up of 21 months. Trial Registration: ClinicalTrials.gov Identifier: NCT01610414.

Multidisciplinary, evidence-based consensus guidelines for human papillomavirus (HPV) vaccination in high-risk populations, Spain, 2016.

INTRODUCTION: Although human papillomavirus (HPV) routine vaccination programmes have been implemented around the world and recommendations have been expanded to include other high-risk individuals, current recommendations often differ between countries in Europe, as well as worldwide. AIM: To find and summarise the best available evidence of HPV vaccination in high-risk patients aiding clinicians and public health workers in the day-to-day vaccine decisions relating to HPV in Spain. METHODS: We conducted a systematic review of the immunogenicity, safety and efficacy/effectiveness of HPV vaccination in high-risk populations between January 2006 and June 2016. HPV vaccination recommendations were established with levels of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: A strong recommendation about HPV vaccination was made in the following groups: HIV infected patients aged 9-26 years; men who have sex with men aged 9-26 years; women with precancerous cervical lesions; patients with congenital bone marrow failure syndrome; women who have received a solid organ transplant or hematopoietic stem cell transplantation aged 9-26 years; and patients diagnosed with recurrent respiratory papillomatosis. CONCLUSIONS: Data concerning non-routine HPV vaccination in populations with a high risk of HPV infection and associated lesions were scarce. We have developed a document to evaluate and establish evidence-based guidelines on HPV vaccination in high-risk populations in Spain, based on best available scientific evidence.

Molecular epidemiology and molecular characterization of respiratory syncytial viruses at a tertiary care university hospital in Catalonia (Spain) during the 2013-2014 season.

BACKGROUND: Human respiratory syncytial virus (HRSV) is the main cause of lower respiratory tract infections among infants and young children. OBJECTIVES: The molecular epidemiology and characterization of HRSV strains detected at a Spanish tertiary hospital during the 2013-2014 season is reported. STUDY DESIGN: Phylogenetic analysis and molecular characterization of HRSV laboratory-confirmed respiratory samples were performed, based on coding sequences of G and F proteins. RESULTS: HRSV infection was laboratory-confirmed in respiratory samples from 320 patients of which 223 (70%) were less than 2 years of age and none undergoing Palivizumab treatment. HRSV was detected at varying levels throughout the season with a maximum rate in the week 52/2013, right before the beginning of the influenza epidemic. Whilst both HRSV groups were found co-circulating, HRSV-B group clearly predominated. The phylogenetic analyses from 139 HVR-2 sequences revealed that most characterized strains belonged to ON1 and BA9 genotypes. Three different phylogenetic subgroups could be distinguished within these genotypes. In addition, three strains (out of the 52 randomly selected) were carrying amino acid substitutions in the epitope A of the F protein, one of them previously related to Palivizumab resistance. CONCLUSIONS: The results of the present study highlight the importance of a continuous HRSV surveillance to monitor not only the introduction of new genotypes on circulation but also the emergence of viral variants with new genetic characteristics that can affect the antigenicity features and the susceptibility to the only current prophylaxis treatment and also for the future development of HRSV vaccines.

First Enterovirus D68 (EV-D68) cases detected in hospitalised patients in a tertiary care university hospital in Spain, October 2014.

Several outbreaks of Enterovirus 68 (EV-D68) have recently been reported in the USA and Canada, causing substantial hospitalisation of children with severe respiratory disease. The acute flaccid paralysis detected in the USA and Canada among children with EV-D68 infection has raised concerns about the aetiological role of this EV serotype in severe neurological disease. The circulation of EV-D68 in the general European population seems to be low, but European Centre for Disease Prevention and Control (ECDC) recommends being vigilant to new cases, particularly in severely ill hospitalised patients. In October 2014, enteroviruses were detected in respiratory samples collected from five hospitalised patients, children and adults. Phylogenetic analysis of partial VP1 sequences confirmed that the detected enteroviruses belonged to the D68 serotype, which were also similar to strains reported in USA (2014). However, all five patients developed respiratory symptoms, but only one required ICU admission. None of the patients described had symptoms of neurological disease. Other considerations related to the detection methods used for the diagnosis of respiratory enteroviruses are also discussed. In conclusion, additional evidence has been provided that supports the role of EV-D68 in respiratory infections in hospitalised patients.

[Use of non-occupational HIV post-exposure prophylaxis in Spain (2001-2005)]. / Demanda y prescripción de la profilaxis postexposición no ocupacional al VIH en España (2001-2005).

BACKGROUND: Non-occupational post-exposure prophylaxis for human immunodeficiency virus (HIV) infection is widely used, although there is little available scientific evidence to support its effectiveness. The aim of this study is to describe the characteristics of the persons exposed, types of exposures, antiretroviral treatment prescribed, and outcome of HIV infection in cases of non-occupational exposure in Spain. METHOD: The data used included all cases of accidental HIV exposure notified to the Non-occupational Post-exposure Prophylaxis Information System between January 2001 and December 2005. Non-occupational exposure to HIV was defined as accidental contact with blood and/or other biological fluids outside the healthcare setting. RESULTS: A total of 993 cases of exposure were notified (569 men [57.3%]); median age was 30 years (range: 1-87). Exposure was sexual in 53.1%, parenteral in 39.8%, and other types in 7.2%. The source person was identified in 82.7% of cases. Antiretroviral treatment (ART) was prescribed in 528 cases (53.2%), with triple therapy in 68.2%. A total of 54.2% returned for the 6-month visit among patients receiving ART and 61.1% among those without this therapy (P < 0.05). One or more side effects developed in 135 (32.4%) cases, and there were 18 treatment interruptions (4.3%). Three seroconversions to HIV were notified (0.3%). CONCLUSIONS: A national registry for monitoring non-occupational post-exposure prophylaxis to HIV is needed because of the high number of cases notified, the considerable incidence of side effects, and the difficulties of follow-up.

Nosocomial transmission of hepatitis C virus during contrast-enhanced computed tomography scanning.

We have investigated two cases of acute hepatitis C that occurred in patients who underwent digestive endoscopy and contrast-enhanced computed tomography (CT) scanning at two different centers. Investigations to identify the sources of infection included an on-site review of diagnostic procedures, interview of the involved healthcare staff, serological testing of the patients who underwent the procedures before and after the index cases and a molecular analysis of viral isolates from the patients and from potential viremic sources. In both cases, the epidemiological investigation identified a chronic hepatitis C virus (HCV) carrier who had been subjected to CT-scanning immediately before the index patient. Genetic distance and molecular phylogenetic analyzes of HCV sequences showed a close relationship between the isolates from these carriers and those from the acute-hepatitis patients, strongly suggesting that patient-to-patient transmission had occurred during CT. This is the first report describing two well documented cases of HCV nosocomial patient-to-patient transmission during contrast-enhanced CT scanning.

Topical anesthesia: possible risk factor for endophthalmitis after cataract extraction.

PURPOSE: To assess the relationship between the risk for acute endophthalmitis after cataract extraction and whether certain factors, such as surgeon qualification, numerical order, duration of surgery, operating theater, and type of anesthesia (topical or retrobulbar), could be modified to decrease the risk. SETTING: Single-center academic practice. METHODS: Two epidemiological studies were performed: a case-control study and a retrospective cohort study. The surgical records of all patients with clinically diagnosed endophthalmitis within 30 days after cataract surgery performed between February 2002 and September 2003 were reviewed. The endophthalmitis cases were compared with 108 randomly selected controls (4 controls per case). The global incidence of endophthalmitis and the incidence according to type of anesthesia were calculated. RESULTS: Of 5011 cataract extractions performed, 27 cases of endophthalmitis occurred. The incidence was 5.39 per 1000 procedures. An independent statistically significant relationship was found between endophthalmitis and the use of topical anesthesia (odds ratio [OR], 11.8; 95% confidence interval [CI], 2.4-58.7) and surgery longer than 45 minutes (OR, 7.2; 95% CI, 1.7-29.7) but not between the other variables. The incidence of endophthalmitis was 1.8 per 1000 cataract extractions with retrobulbar anesthesia and 6.76 per 1000 with topical anesthesia (relative risk [RR], 3.76; 95% CI, 0.89-15.85). After the start of the study period was extended to May 2001, the incidence of endophthalmitis was 1.3 per 1000 cataract extractions with retrobulbar anesthesia and 8.7 per 1000 with topical anesthesia (RR, 6.72; 95% CI, 1.63-27.63). CONCLUSION: Results suggest that there may be an association between topical anesthesia and endophthalmitis after cataract extraction.