Equivalent immunogenicity across three RSVpreF vaccine lots in healthy adults 18-49 years of age: Results of a randomized phase 3 study.

BACKGROUND: Bivalent RSV prefusion F subunit vaccine (RSVpreF), comprised of equal quantities of stabilized prefusion F antigens from the major circulating subgroups (RSV A, RSV B), is licensed for prevention of RSV-associated lower respiratory tract illness (LRTI) in older adults and for maternal vaccination for prevention of RSV-associated LRTI in infants. To support licensure and large-scale manufacturing, this lot consistency study was conducted to demonstrate equivalence in immunogenicity across 3 RSVpreF lots. METHODS: This phase 3, multicenter, parallel-group, placebo-controlled, randomized (1:1:1:1), double-blind study evaluated immunogenicity, safety, and tolerability of RSVpreF in healthy 18-49-year-old adults. Participants received a single 120-µg injection of 1 of 3RSVpreF lots or placebo. Geometric mean ratio (GMR) of RSV serum 50 % neutralizing geometric mean titers obtained 1 month after vaccination were compared between each vaccine lot for RSV A and RSV B, separately. Equivalence between lots was defined using a 1.5-fold criterion (GMR 95 % CIs for every lot pair within the 0.667-1.5 interval). Safety and tolerability were assessed. RESULTS: Of 992participants vaccinated, 948 were included in the evaluable immunogenicity population. All 3 RSVpreF lots elicited strong immune responses, meeting the 1.5-fold equivalence criterion for all between-lot comparisons for both RSV A and RSV B. Across the 3 lots, RSV A and RSV B 50 % neutralizing geometric mean titers substantially increased from baseline (RSV A, 1671-1795; RSV B 1358-1429) to 1 month after RSVpreF vaccination (RSV A, 24,131-25,238; RSV B, 19,238-21,702), corresponding to ≥14-fold increases in 50 % neutralizing titers for both RSV A and RSV B from before to 1 month after vaccination. Single doses of RSVpreF were safe and well tolerated, with similar safety profiles across the 3 RSVpreF lots. CONCLUSIONS: These findings support the reproducibility of RSVpreF vaccine manufacturing with similar safety and reactogenicity profiles (NCT05096208).

Efficacy of a 4-Antigen Staphylococcus aureus Vaccine in Spinal Surgery: The STaphylococcus aureus suRgical Inpatient Vaccine Efficacy (STRIVE) Randomized Clinical Trial.

BACKGROUND: Staphylococcus aureus is a global pathogen that is frequently responsible for healthcare-associated infections, including surgical site infections (SSIs). Current infection prevention and control approaches may be limited, with S. aureus antibiotic resistance remaining problematic. Thus, a vaccine to prevent or reduce S. aureus infection is critically needed. We evaluated the efficacy and safety of an investigational 4-antigen S. aureus vaccine (SA4Ag) in adults undergoing elective open posterior spinal fusion procedures with multilevel instrumentation. METHODS: In this multicenter, site-level, randomized, double-blind trial, patients aged 18-85 years received a single dose of SA4Ag or placebo 10-60 days before surgery. SA4Ag efficacy in preventing postoperative S. aureus bloodstream infection and/or deep incisional or organ/space SSIs was the primary end point. Safety evaluations included local reactions, systemic events, and adverse events (AEs). Immunogenicity and colonization were assessed. RESULTS: Study enrollment was halted when a prespecified interim efficacy analysis met predefined futility criteria. SA4Ag showed no efficacy (0.0%) in preventing postoperative S. aureus infection (14 cases in each group through postoperative day 90), despite inducing robust functional immune responses to each antigen compared with placebo. Colonization rates across groups were similar through postoperative day 180. Local reactions and systemic events were mostly mild or moderate in severity, with AEs reported at similar frequencies across groups. CONCLUSIONS: In patients undergoing elective spinal fusion surgical procedures, SA4Ag was safe and well tolerated but, despite eliciting substantial antibody responses that blocked key S. aureus virulence mechanisms, was not efficacious in preventing S. aureus infection. Clinical Trials Registration. NCT02388165.

A Phase 1/2 Study of a Respiratory Syncytial Virus Prefusion F Vaccine With and Without Adjuvant in Healthy Older Adults.

BACKGROUND: Respiratory syncytial virus (RSV) is an important cause of disease in older adults. We evaluated the safety and immunogenicity of a stabilized RSV prefusion F subunit (RSVpreF) vaccine candidate with/without adjuvant in adults aged 65-85 years. METHODS: Primary cohort participants were equally randomized to 1 of 7 RSVpreF formulations: 60 µg with either Al(OH)3 or CpG/Al(OH)3, 120 µg with either Al(OH)3 or CpG/Al(OH)3, 240 µg with either Al(OH)3 or CpG/Al(OH)3, 240 µg unadjuvanted, or placebo, administered concomitantly with high-dose seasonal inactivated influenza vaccine (SIIV). Participants in the month 0,2 cohort were randomized to RSVpreF 240 µg with CpG/Al(OH)3 or placebo, administered at months 0 and 2. RESULTS: All RSVpreF vaccine candidates elicited robust and persistent serum neutralizing responses when administered alone or with SIIV. There was no notable difference in neutralizing response between the formulations, including those containing CpG. In the month 0,2 cohort, there was no booster effect of dose 2. SIIV responses were similar or slightly lower with concomitant administration of RSVpreF. Most systemic and local reactions were mild and more frequent after RSVpreF than placebo. CONCLUSIONS: RSVpreF formulations were well tolerated and elicited robust neutralizing responses in older adults; however, CpG/Al(OH)3 did not further enhance responses. Clinical Trials Registration. NCT03572062.

Prefusion F Protein-Based Respiratory Syncytial Virus Immunization in Pregnancy.

BACKGROUND: Respiratory syncytial virus (RSV), a major cause of illness and death in infants worldwide, could be prevented by vaccination during pregnancy. The efficacy, immunogenicity, and safety of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine in pregnant women and their infants are uncertain. METHODS: In a phase 2b trial, we randomly assigned pregnant women, at 24 through 36 weeks' gestation, to receive either 120 or 240 µg of RSVpreF vaccine (with or without aluminum hydroxide) or placebo. The trial included safety end points and immunogenicity end points that, in this interim analysis, included 50% titers of RSV A, B, and combined A/B neutralizing antibodies in maternal serum at delivery and in umbilical-cord blood, as well as maternal-to-infant transplacental transfer ratios. RESULTS: This planned interim analysis included 406 women and 403 infants; 327 women (80.5%) received RSVpreF vaccine. Most postvaccination reactions were mild to moderate; the incidence of local reactions was higher among women who received RSVpreF vaccine containing aluminum hydroxide than among those who received RSVpreF vaccine without aluminum hydroxide. The incidences of adverse events in the women and infants were similar in the vaccine and placebo groups; the type and frequency of these events were consistent with the background incidences among pregnant women and infants. The geometric mean ratios of 50% neutralizing titers between the infants of vaccine recipients and those of placebo recipients ranged from 9.7 to 11.7 among those with RSV A neutralizing antibodies and from 13.6 to 16.8 among those with RSV B neutralizing antibodies. Transplacental neutralizing antibody transfer ratios ranged from 1.41 to 2.10 and were higher with nonaluminum formulations than with aluminum formulations. Across the range of assessed gestational ages, infants of women who were immunized had similar titers in umbilical-cord blood and similar transplacental transfer ratios. CONCLUSIONS: RSVpreF vaccine elicited neutralizing antibody responses with efficient transplacental transfer and without evident safety concerns. (Funded by Pfizer; ClinicalTrials.gov number, NCT04032093.).

Staphylococcus aureus infections after elective pediatric surgeries.

OBJECTIVE: To determine the 180-day cumulative incidence of culture-confirmed Staphylococcus aureus infections after elective pediatric surgeries. DESIGN: Retrospective cohort study utilizing the Premier Healthcare database (PHD). SETTING: Inpatient and hospital-based outpatient elective surgical discharges. PATIENTS: Pediatric patients <18 years who underwent surgery during elective admissions between July 1, 2010, and June 30, 2015, at any of 181 PHD hospitals reporting microbiology results. METHODS: In total, 74 surgical categories were defined using ICD-9-CM and CPT procedure codes. Microbiology results and ICD-9-CM diagnosis codes defined S. aureus infection types: bloodstream infection (BSI), surgical site infection (SSI), and other types (urinary tract, respiratory, and all other). Cumulative postsurgical infection incidence was calculated as the number of infections divided by the number of discharges with qualifying elective surgeries. RESULTS: Among 11,874 inpatient surgical discharges, 180-day S. aureus infection incidence was 1.79% overall (1.00% SSI, 0.35% BSI, 0.45% other). Incidence was highest among children <2 years of age (2.76%) and lowest for those 10-17 years (1.49%). Among 50,698 outpatient surgical discharges, incidence was 0.36% overall (0.23% SSI, 0.05% BSI, 0.08% others); it was highest among children <2 years of age (0.57%) and lowest for those aged 10-17 years (0.30%). MRSA incidence was significantly higher after inpatient surgeries (0.68%) than after outpatient surgeries (0.14%; P < .0001). Overall, the median days to S. aureus infection was longer after outpatient surgery than after inpatient surgery (39 vs. 31 days; P = .0116). CONCLUSIONS: These findings illustrate the burden of postoperative S. aureus infections in the pediatric population, particularly among young children. These results underscore the need for continued infection prevention efforts and longer-term surveillance after surgery.

Invasive Staphylococcus aureus Infection among Patients Undergoing Elective, Posterior, Instrumented Spinal Fusion Surgeries: A Retrospective Cohort Study.

Background: Post-surgical invasive Staphylococcus aureus infections among spinal fusion patients are serious complications that can worsen clinical outcomes and increase healthcare utilization. Risk of such infections at the population level remains unknown. This study assessed the post-surgical risk of invasive Staphylococcus aureus infections among patients undergoing elective posterior instrumented spinal fusion surgeries in 129 U.S. hospitals. Patients and Methods: This retrospective cohort study analyzed adult patients ≥18 years of age who underwent thoracolumbar/lumbar and cervical fusion surgeries during 2010 - 2014 using the Premier Healthcare Database, the largest hospital discharge database in the United States. Risks of blood stream infection (BSI), deep or organ/space surgical site infections (SSI) caused by Staphylococcus aureus during 90 and 180 days post-index surgery were estimated. Infections were identified based on positive culture results, related International Classification of Diseases, Ninth Revision (ICD-9) procedure codes, and specific claims information. Results: Among 11,236 patients with thoracolumbar/lumbar fusion, 90- and 180-day BSI/SSI infection risks were higher for multilevel than single level fusion (90-day, 1.52% vs. 1.07%, p = 0.05; 180-day, 1.66% vs. 1.07%, p = 0.014). Among 1,641 patients with cervical fusion, 90- and 180-day BSI/SSI infection risks were also higher in multilevel fusions but not statistically significant (90-day, 1.66% vs. 0.52%, p = 0.350; 180-day, 1.80% vs. 0.51%, p = 0.241). The risk for SSI/BSI was more than twice as high among multilevel thoracolumbar/lumbar fusion patients with more than two comorbidities than those with no comorbidity at both 90-day (2.78% vs. 1.00%, p < 0.05) and 180-day (3.01% vs. 1.10%, p < 0.05). Similar trend without statistical significance was seen in multilevel cervical fusion cohort (90-day, 2.91% vs. 1.25%, p > 0.05; 180-day, 3.88% vs. 1.41%, p > 0.05). Conclusions: The risk of BSI/SSI infection for elective posterior instrumented spinal fusions ranged between 0.5% and 2%. Higher risk was observed in multilevel thoracolumbar/lumbar surgery, with infection risk greatest in patients with more than two comorbidities. These real-world findings highlight the need for additional measures, in addition to antibiotic prophylaxis, to reduce invasive Staphylococcus aureus infections in this setting.

A Randomized Phase 1/2 Study of a Respiratory Syncytial Virus Prefusion F Vaccine.

BACKGROUND: Protection against human respiratory syncytial virus (RSV) remains an unmet need potentially addressable by maternal immunization. This phase 1/2 study evaluated a bivalent prefusion F vaccine (RSVpreF) with antigens from RSV subgroups A and B. METHODS: Adults 18-49 years old (N = 618) were randomized to receive placebo or 60, 120, or 240 µg RSVpreF with or without Al(OH)3. Safety and immunogenicity were evaluated. RESULTS: RSVpreF recipients more frequently reported local reactions and systemic events than placebo recipients; these were mostly mild or moderate. No vaccine-related serious adverse events occurred through 12 months postvaccination. All RSVpreF formulations induced 1-month postvaccination virus-neutralizing titers higher than those associated with protection of high-risk infants by palivizumab, the only prophylactic currently available for RSV. Geometric mean fold rises (GMFRs) across RSVpreF doses/formulations were 10.6-16.9 for RSV A and 10.3-19.8 for RSV B at 1 month postvaccination, greater than those historically elicited by postfusion F vaccines. GMFRs were 3.9-5.2 and 3.7-5.1, respectively, at 12 months postvaccination. CONCLUSIONS: RSVpreF formulations were safe, well tolerated, and induced robust neutralizing responses in adults. These findings support development of RSVpreF, which is being evaluated in a pivotal phase 3 study for maternal immunization. CLINICAL TRIALS REGISTRATION: NCT03529773.

Epidemiology of Invasive Escherichia coli Infection and Antibiotic Resistance Status Among Patients Treated in US Hospitals: 2009-2016.

BACKGROUND: Published data is limited on the prevalence and risk of recurrence of extraintestinal invasive Escherichia coli infections (IEIs) in the United States. METHODS: The analysis included all inpatient and hospital-based outpatient visits occurring between 2009 and 2016 at hospitals with continuous microbiology data submission to the Premier Healthcare Database for 90 days before and 12 months after the admission or visit. IEI was defined as having positive E. coli culture from a normally sterile site (eg, blood, cerebrospinal fluid). The prevalence of IEI, 12-month risk of recurrent IEI, and antibiotic resistance were assessed. RESULTS: Overall, 144 944 725 hospital visits among 37 207 510 patients were analyzed, and 71 909 IEI events occurred in 67 583 patients, corresponding to an IEI prevalence of 0.50 events per 1000 visits and 1.82 events per 1000 patients. Recurrence was common: 26.9 per 1000 patients had a recurrent IEI in the 12 months after their infection. Most infections were community acquired (66.4%), and urosepsis was most common clinical syndrome (66.0%). The 30-day risk of IEI among patients undergoing transrectal ultrasound-guided prostate biopsy was high: 5.03 events per 1000 patients. Among all IEI cases with antibiotic susceptibility testing, 9.18% were resistant to extended-spectrum cephalosporins, 28.22% to fluoroquinolones, and 0.14% to carbapenems. Resistance to extended-spectrum cephalosporins increased from 5.46% to 12.97% during the 8-year study period. CONCLUSIONS: This real-world study indicates a substantial burden of IEI and recurrent IEI exists in the United States, as well as increasing resistance to extended-spectrum cephalosporins. Future research should explore risk factors of recurrent IEI aiming to effectively prevent such infections.

The incidence of stroke among selected patients undergoing elective posterior lumbar fusion: a retrospective cohort study.

BACKGROUND: Although stroke is a rare complication among spinal surgery patients, the recognition of this adverse event is critical given the aging population undergoing surgical procedures. The objective of this study was to estimate the incidence of stroke among selected adults undergoing elective posterior lumbar fusion (PLF) during various post-operative risk windows and among different subgroups. METHODS: A retrospective cohort study using a longitudinal electronic healthcare record (EHR) database was conducted from January 1, 2007 to June 30, 2018. Elective PLF, stroke, and select clinical characteristics were defined based on International Classification of Disease codes. Patients aged 18 to 85 years with ≥183 days of enrollment in the database prior to undergoing elective PLF were followed from the index date until the occurrence of stroke, death, loss to follow-up, or end of study period, whichever occurred first. The incidence of stroke was estimated in the following risk windows: index hospitalization, ≤ 30 days, ≤ 90 days, ≤ 180 days, and ≤ 365 days post-operation. RESULTS: A total of 43,063 patients were eligible for the study. The incidence of stroke following elective PLF was 0.29% (95% confidence interval [CI]: 0.25, 0.35%) during index hospitalization, 0.44% (95% CI: 0.38, 0.50%) ≤ 30 days, 0.59% (95% CI: 0.52, 0.67%) ≤ 90 days, 0.76% (95% CI: 0.68, 0.85%) ≤ 180 days, and 1.12% (95% CI: 1.03, 1.23%) ≤ 365 days post-operation. Stratified analyses revealed that older patients had a higher incidence of stroke. Additionally, black patients had higher stroke incidences. Post-operative stroke incidence was higher among patients with a history of type 2 diabetes than among patients without such history; similarly, stroke incidence was higher among patients with a history of stroke compared to patients without such history. CONCLUSIONS: The incidence of stroke following elective PLF using an EHR database in this study is slightly higher than that reported in the literature. Our results suggest that stroke risk modification prior to PLF may be important for patients who are older, black, type 2 diabetic, and/or have a history of stroke.

Safety, tolerability, and immunogenicity of a novel 4-antigen Staphylococcus aureus vaccine (SA4Ag) in healthy Japanese adults.

A novel Staphylococcus aureus 4-antigen vaccine (SA4Ag) is under development, comprising capsular polysaccharide serotypes 5 and 8 (CP5 and CP8) conjugated to CRM197, recombinant protein clumping factor A (rmClfA), and recombinant manganese transporter protein C (MntC). We evaluated SA4Ag safety, tolerability, and immunogenicity in Japanese adults aged 20 to 64 and 65 to 85 years. A total of 136 healthy Japanese adults (68 per age group) were randomized 1:1 to receive single-dose SA4Ag or placebo intramuscularly (Day 1). Safety assessments included reactogenicity and adverse events. The ability of the vaccine to induce immune responses that are considered functional due to their ability to facilitate the killing of S. aureus or neutralize S. aureus virulence mechanisms was assessed using 5 different antigen-specific assays. SA4Ag was well tolerated in both age groups, with no safety concerns. At Day 29, > 85% of SA4Ag recipients in each age group achieved predefined thresholds for each antigen. Antibody geometric mean-fold rises from baseline to Day 29 in SA4Ag groups were: > 80 and > 30 for CP5 and CP8 (opsonophagocytic activity assay), > 10 for ClfA (fibrinogen-binding inhibition assay), and > 15 and > 7 for ClfA and MntC (competitive Luminex® immunoassay), respectively. Antibody titers decreased through Month 12 but remained well above baseline and placebo levels. SA4Ag had an acceptable safety profile and induced rapid and robust functional immune responses in both age groups. These results support ongoing development of SA4Ag for the prevention of invasive S. aureus disease in elective-surgery patients in Japan, North America, and Europe.

Neutrophil killing of Staphylococcus aureus in diabetes, obesity and metabolic syndrome: a prospective cellular surveillance study.

BACKGROUND: Obesity, metabolic syndrome (MetS), and diabetes are frequent in surgical populations and can enhance susceptibility to postoperative surgical site infections. Reduced neutrophil function has been linked with diabetes and risk of Staphylococcus aureus infection. Therefore, neutrophil function in diabetic and obese subjects (± MetS) was assessed in this prospective serological and cellular surveillance study to determine whether vaccines administered to protect against infections after surgery could be effective in these populations. METHODS: Neutrophil function (chemotaxis, phagocytosis, and opsonophagocytic killing of S. aureus) was assessed in subjects classified according to diabetes status, body mass index, and presence/absence of MetS. Neutrophils were characterized within functional subsets by flow cytometry. A serologic assay was used to measure baseline antibody presence to each antigen in SA4Ag: capsular polysaccharide (CP) type 5, CP8, recombinant mutant Clumping factor A (rmClfA), and recombinant Manganese transport protein C (rMntC). RESULTS: Neutrophil function was similar for comorbid and healthy cohorts, with no significant between-group differences in cell counts, migration, phagocytosis ability, neutrophil subset proportions, and S. aureus killing ability when neutrophils were isolated 3-6 months apart (Visit 1 [n = 90] and Visit 2 [n = 70]) and assessed. Median pre-existing antibody titers to CP5, CP8, and rmClfA were comparable for all cohorts (insufficient subjects with rMntC titers for determination). CONCLUSIONS: MetS, diabetes, and obesity do not impact in vitro neutrophil function with regard to S. aureus killing, suggesting that if an effective S. aureus vaccine is developed it may be effective in individuals with these comorbidities.

A randomized study of fever prophylaxis and the immunogenicity of routine pediatric vaccinations.

OBJECTIVE: Prophylactic antipyretic use during pediatric vaccination is common. This study assessed whether paracetamol or ibuprofen prophylaxis interfere with immune responses to the 13-valent pneumococcal conjugate vaccine (PCV13) given concomitantly with the combined DTaP/HBV/IPV/Hib vaccine. METHODS: Subjects received prophylactic paracetamol or ibuprofen at 0, 6-8, and 12-16 h after vaccination, or 6-8 and 12-16 h after vaccination at 2, 3, 4, and 12months of age. At 5 and 13months, immune responses were evaluated versus responses in controls who received no prophylaxis. RESULTS: After the infant series, paracetamol recipients had lower levels of circulating serotype-specific pneumococcal anticapsular immunoglobulin G than controls, reaching significance (P<0.0125) for 5 serotypes (serotypes 3, 4, 5, 6B, and 23F) when paracetamol was started at vaccination. Opsonophagocytic activity assay (OPA) results were similar between groups. Ibuprofen did not affect pneumococcal responses, but significantly (P<0.0125) reduced antibody responses to pertussis filamentous hemagglutinin and tetanus antigens after the infant series when started at vaccination. No differences were observed for any group after the toddler dose. CONCLUSIONS: Prophylactic antipyretics affect immune responses to vaccines; these effects vary depending on the vaccine, antipyretic agent, and time of administration. In infants, paracetamol may interfere with immune responses to pneumococcal antigens, and ibuprofen may reduce responses to pertussis and tetanus antigens. The use of antipyretics for fever prophylaxis during infant vaccination merits careful consideration. ClinicalTrials.gov identifier: NCT01392378https://clinicaltrials.gov/ct2/show/NCT01392378?term=NCT01392378&rank=1.

13-valent pneumococcal conjugate vaccine (PCV13) is immunogenic and safe in children 6-17 years of age with sickle cell disease previously vaccinated with 23-valent pneumococcal polysaccharide vaccine (PPSV23): Results of a phase 3 study.

BACKGROUND: A large population of older children with sickle cell disease (SCD) is currently vaccinated with only 23-valent pneumococcal polysaccharide vaccine (PPSV23). In immunocompetent adults, PPSV23 vaccination reduces immune responses to subsequent vaccination with a pneumococcal vaccine. The 13-valent pneumococcal conjugate vaccine (PCV13), which addresses this limitation, may offer an advantage to this population at high risk of pneumococcal disease. PROCEDURE: Children with SCD 6-17 years of age previously vaccinated with PPSV23 at least 6 months before study enrollment received two doses of PCV13 6 months apart. Anti-pneumococcal polysaccharide immunoglobulin G (IgG) geometric mean concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers (GMTs) were measured before, 1 month after each administration, and 1 year after the second administration. RESULTS: Following each PCV13 administration, IgG GMCs and OPA GMTs significantly increased, and antibody levels after doses 1 and 2 were generally comparable. Antibody levels declined over the year following dose 2. At 1 year after the second administration, OPA GMTs for all and IgG GMCs for most serotypes remained above pre-vaccination levels. Most adverse events were due to vaso-occlusive crises, a characteristic of the underlying condition of SCD. CONCLUSIONS: Children with SCD who were previously vaccinated with PPSV23 responded well to 1 PCV13 dose, and a second dose did not increase antibody response. PCV13 antibodies persisted above pre-vaccination levels for all serotypes 1 year after dose 2. Children with SCD may benefit from at least one dose of PCV13.

Immunogenicity and Safety of 13-Valent Pneumococcal Conjugate Vaccine in HIV-Infected Adults Previously Vaccinated With Pneumococcal Polysaccharide Vaccine.

BACKGROUND: Persons with human immunodeficiency virus (HIV) infection are at increased risk of pneumococcal disease. We evaluated the safety and immunogenicity of 13-valent pneumococcal conjugate vaccine (PCV13) in this population. METHODS: HIV-infected persons ≥ 18 years of age who were previously vaccinated with ≥ 1 dose of 23-valent pneumococcal polysaccharide vaccine (PPSV23) and had CD4 cell counts ≥ 200 cells/mm(3) and HIV viral loads <50 000 copies/mL were enrolled in this 3-dose PCV13 open-label study. RESULTS: A total of 329 subjects received ≥ 1 dose, and 279 received 3 doses administered at 6-month intervals. Increases in anticapsular polysaccharide immunoglobulin G concentrations and opsonophagocytic antibody titers were demonstrated 1 month after each of the 3 doses of PCV13. Antibody levels were generally similar after each dose. The responses were similar whether subjects had previously received 1 or ≥ 2 doses of PPSV23. Pain at the injection-site was the most common local reaction. Severe injection site or systemic events were uncommon. CONCLUSIONS: Vaccination with PCV13 induces anticapsular immunoglobulin G and opsonophagocytic antibody responses in HIV-infected adults with prior PPSV23 vaccination and CD4 cell counts ≥ 200 cells/mm(3). The observations support the use of PCV13 in this population. CLINICAL TRIALS REGISTRATION: NCT00963235.

Adherencia a las terapias antirretrovirales en una población de bajos recursos económicos de la región suburbana de Buenos Aires / Adherence to the antiretroviral therapy in a low income population of the suburban area of Buenos Aires

Es necesario un elevado nivel de adherencia a la terapia antirretroviral para obtener beneficios a largo plazo. Mediante una encuesta previamente validada, evaluamos el nivel de adherencia a la terapia antirretroviral y exploramos posibles factores relacionados con la no adherencia en una población de bajos recursos económicos. Realizamos un estudio transversal en la población de pacientes infectados con VIH que reciben terapia antirretroviral. Se evaluaron variables sociodemográficas y sociocognitivas. El nivel de adherencia se determinó según el número de dosis perdidas los cuatro días previos a la entrevista. Se utilizaron prueba de Chi cuadrado o exacta de Fisher para variables nominales y prueba t de Student para variables continuas para evaluar diferencias estadísticamente significativas. Participaron 71 pacientes: mujeres 41 (58%), media de edad: 35.3 años;. hombres 30 (42%), media de edad 40.4 años. Cincuenta reportaron adherencia > 95% (70.4%). La carga viral fue < 500 copias/ml en 80.4% de los pacientes adherentes y en 34% de los no adherentes. Sentirse a menudo o siempre, sin ánimo, triste y/o deprimido la semana previa a la entrevista se asoció estadísticamente con adherencia < 95%. No se asociaron con el nivel de adherencia, edad, género, nivel de educación, poseer empleo, factor de riesgo de adquisición de VIH, uso de alcohol, uso de drogas ilegales, presencia de síntomas, capacidad de autodeterminación, comprender la asociación entre adherencia y resistencia, apoyo social y familiar, número de comprimidos o tomas y recibir un régimen que contiene Inhibidor de Proteasa.

[Occupational exposure to hepatitis C virus]. / Exposicion ocupacional al virus de hepatitis C.

Occupational exposure to Hepatitis C virus is an area of growing concern due to a lack of prophylaxis and limited knowledge regarding prevalence in hospital environment. Between 1999 and 2003, a total of 128 occupational exposures to this virus were registered in Diego Paroissien Hospital, eight of which led to hepatitis (6.3%) and one case to serum conversion (0.8%). Currently there is no preventive therapy and great interest is focused on acute infection therapy the effectiveness of which is still controversial. This study reinforces the fact that adherence to the Universal Precautions is still the most important preventive measure for health care workers, and the most cost beneficial.

Exposicion ocupacional al virus de hepatitis c / Occupational exposure to hepatitis C virus

La transmisión ocupacional de virus de hepatitis C (VHC) es un área de creciente preocupacióndada la falta de profilaxis y la poca información de su prevalencia en el medio hospitalario. Sobre128 exposiciones ocupacionales ocurridas en el Hospital Diego Paroissien entre1999 y 2003 hubieron 8 casosde exposición a VHC (6.3%) y un caso de seroconversión posterior a la exposición (0.8%). No existiendo en laactualidad terapia preventiva para VHC resulta de gran interés la posibilidad de tratamiento de la infección aguda.La mayor parte de los autores coincide en recomendar el tratamiento del episodio agudo de hepatitis porVHC basado en la evidencia actual, aunque aún no está bien definida la mejor estrategia diagnóstica y terapéutica.El acatamiento de las Normas de Precauciones Universales sigue siendo en la actualidad la más importantemedida preventiva para evitar la infección ocupacional por VHC en el personal de salud y la de mejor equilibriocosto-beneficio.

Occupational exposure to Hepatitis C virus is an areaof growing concern due to a lack of prophylaxis and limited knowledge regarding prevalence in hospitalenvironment. Between 1999 and 2003, a total of 128 occupational exposures to this virus were registeredin Diego Paroissien Hospital, eight of which led to hepatitis (6.3%) and one case to serum conversion (0.8%).Currently there is no preventive therapy and great interest is focused on acute infection therapy the effectivenessof which is still controversial. This study reinforces the fact that adherence to the Universal Precautions is stillthe most important preventive measure for health care workers, and the most cost beneficial.

JC virus granule cell neuronopathy: A novel clinical syndrome distinct from progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) typically affects the CNS white matter of the central nervous system. We present an human immunodeficiency virus-infected patient with polyomavirus JC infection restricted to granule cell neurons of the cerebellum and with corresponding neurological symptomatology. Magnetic resonance imaging demonstrated cerebellar atrophy without white matter lesions and stereotactic biopsy showed selective infection of the cerebellar granular cell layer, with preservation of Purkinje cells and absence of classic progressive multifocal leukoencephalopathy histopathology in underlying white matter. Evolution over 8 years was marked by symptomatic improvement corresponding to highly active antiretroviral therapy (HAART), with modest increase in CD4(+) T-cell counts. We propose to call this novel syndrome JCV granule cell neuronopathy (JCV GCN).

Profilaxis antibiótica en área quirúrgica. Eficacia de un programa de control y entrenamiento / Use of prophylactic antibiotics in the surgical area

La utilidad de la profilaxis antibiótica en la prevención de infecciones del sitio quirúrgico ha sido demostrada por diversos autores. aproximadamente un 30 por ciento de los antibióticos en hospitales son utilizados para profilaxis. Sin embargo, diversos estudios muestran que solo en alrededor del 40 por ciento de los casos se usan adecuadamente. El objetivo es evaluar el impacto de un programa de control y entrenamiento sobre el uso de antibióticos en cirugía limpia y limpia-contaminada