Reduced risk of pertussis among persons ever vaccinated with whole cell pertussis vaccine compared to recipients of acellular pertussis vaccines in a large US cohort.

BACKGROUND: Unexpected waning of immunity after pertussis vaccination is now well described. In this study we examined whether prior vaccination with whole-cell pertussis vaccine (wP) at any point provided superior protection contrasted with a solely acellular pertussis vaccine (aP) series. We utilized the coincidence of a large outbreak of pertussis with the termination of wP availability, providing populations of children who had been vaccinated with combinations of wP and aP. METHODS: Kaiser Permanente (KP) is an integrated healthcare system with complete electronic records and a centralized laboratory. Cases of laboratory-confirmed pertussis and vaccination data for members aged 8-20 years were retrieved. RESULTS: Among 263 496 persons aged 8-20 years, 904 cases of pertussis were identified. In patients with a full history of vaccinations administered by KP, those with 5 total doses of only aP had an 8.57 relative risk (RR) of pertussis (P < .0001) contrasted to those with ≥1 wP dose. With 6 doses of aP, the RR of disease was 3.55 (P < .0001). When external vaccine records were included, the results were similar. CONCLUSIONS: We found a markedly increased risk of disease associated with an entirely aP series. This risk was mitigated, but not eliminated, by the presence of a sixth dose of pertussis vaccine (Tdap). Receipt of 1 or more wP doses markedly augmented the durability of immunity from subsequent aP doses. It appears that a wholly acellular pertussis vaccine series is significantly less effective and durable than one that contains the traditional whole cell vaccine.

Unexpectedly limited durability of immunity following acellular pertussis vaccination in preadolescents in a North American outbreak.

BACKGROUND: Despite widespread childhood vaccination against Bordetella pertussis, disease remains prevalent. It has been suggested that acellular vaccine may be less effective than previously believed. During a large outbreak, we examined the incidence of pertussis and effectiveness of vaccination in a well-vaccinated, well-defined community. METHODS: Our center provides care to 135 000 patients, 40% of the population of Marin County, California. A total of 171 patients tested positive for B. pertussis from 1 March to 31 October 2010 by polymerase chain reaction (PCR). Electronic medical records were reviewed for demographic characteristics and vaccination status. RESULTS: We identified 171 cases of clinical pertussis, 132 of which were in pediatric patients. There was a notable increase in cases among patients aged 8-12 years. The rate of testing peaked among infants but remained relatively constant across ages until 12 years. The rate of positive tests was low for ages 0-6 years and increased among preadolescents, peaking among those aged 12 years. The vaccination rate among PCR-positive preadolescents were approximately equal to that of controls. The vaccine effectiveness was 41%, 24%, and 79% for children aged 2-7 years, 8-12 years, 13-18 years, respectively. CONCLUSIONS: Our data suggests that the current schedule of acellular pertussis vaccine doses is insufficient to prevent outbreaks of pertussis. We noted a markedly increased rate of disease from ages 8-12 years, proportionate to the interval since the last scheduled vaccine. Stable rates of testing ruled out selection bias. The possibility of earlier or more numerous booster doses of acellular pertussis vaccine either as part of routine immunization or for outbreak control should be entertained.

The Impact of Therapeutic Hypothermia Used to Treat Anoxic Brain Injury After Cardiopulmonary Resuscitation on Organ Donation Outcomes.

Therapeutic hypothermia (TH) is clinically used to improve neurologic outcomes in patients with anoxic brain injury after cardiopulmonary resuscitation (CPR). For patients that regress and become organ donors after neurologic determination of death (DNDDs), the impact of TH received before determination of death on organ donation outcomes remains unknown. A prospective observational study of all adult DNDDs that received CPR and had anoxia as a cause of death from March 2013 to December 2014 was conducted across 20 organ procurement organizations (OPOs) in the United States. Main outcome measures included organs transplanted per donor (OTPD), specific organ transplantation rates, and recipient graft outcomes. One thousand ninety eight DNDDs met inclusion criteria, with 46% having received TH before determination of death. DNDDs with hypothermia before death had a similar number of OTPD (2.74 vs. 2.69, p = 0.61) and similar transplantation rates of individual organs. With regards to recipients, there was significantly less delayed graft function (DGF) in kidney grafts from donors who received TH before death (24% vs. 30%, p = 0.02). After adjusting for donor, recipient, and graft related factors, the protective effect of TH on DGF persisted (OR 0.75, 95%CI [0.56-0.995], p = 0.046). TH before death in the donor is independently associated with a 25% decrease in DGF among kidney recipients. This should be considered a protective donor selection factor in guiding the decision to accept or reject an organ for transplantation.

Eight- or 12-Week Treatment of Hepatitis C with Ledipasvir/Sofosbuvir: Real-World Experience in a Large Integrated Health System.

BACKGROUND: Second-generation direct-acting antiviral agents are integral to treatment of hepatitis C (HCV) infection. Eight-week courses of ledipasvir/sofosbuvir (LDV/SOF) have been supported in some studies, but data are limited on efficacy in real-world use. Controversy exists regarding applicability of clinical trials to real-world effectiveness. We report virologic responses of patients with HCV genotype 1 infection receiving LDV/SOF for 8 or 12 weeks in a large integrated healthcare system. METHODS: All patients receiving LDV/SOF, without ribavirin, were identified from pharmacy records, and outcomes are reported. Only treatment-naïve patients without evidence of cirrhosis and hepatitis C viral load less than 6 million IU/ml were candidates for 8-week therapy. Treatment was at clinician discretion, but delivered by a multidisciplinary team and reviewed for appropriateness and adherence to these criteria by one of the authors, all experienced in hepatitis C treatment. Sustained viral response at 12 weeks (SVR 12) was contrasted between those receiving 8 and those receiving 12 weeks of treatment. RESULTS: Completed prescriptions for LDV/SOF, without ribavirin, as of 30 September 2015 were identified in 1021 patients. Five patients discontinued therapy due to medical reasons and 35 had incomplete follow-up viral load data, thus there were 981 evaluable patients: 377 treated for 8 weeks and 604 treated for 12 weeks. SVR 12 was virtually identical at 93.6 and 93.5%, respectively. Baseline characteristics differed between the two groups, as only treatment-naïve, non-cirrhotic, non-HIV-infected patients were eligible for an 8-week course of therapy. CONCLUSIONS: Eight-week courses of LDV/SOF are comparable to 12-week courses in real-world use among selected patients supported by a multidisciplinary team.