Jennifer A. Whitaker

Strategies to increase responsiveness to hepatitis B vaccination in adults with HIV-1

HIV and hepatitis B virus co-infection leads to substantially increased morbidity and mortality compared with either infection alone. Immunisation with hepatitis B virus vaccine is the most effective way to prevent the infection in people with HIV; however, these patients have decreased vaccine responses and a short duration of protection compared with immunocompetent individuals. Control of HIV replication with highly active antiretroviral therapy and increased CD4 cell counts are associated with improved immune responses to hepatitis B vaccination. New vaccination strategies, such as increased vaccine dose, use of the intradermal route, and addition of adjuvants, could improve response rates in adults with HIV.

Prevalence and Incidence of Latent Tuberculosis Infection in Georgian Healthcare Workers

Background Tuberculosis is a major occupational hazard in low and middle-income countries. Limited data exist on serial testing of healthcare workers (HCWs) with interferon-γ release assays (IGRAs) for latent tuberculosis infection (LTBI), especially in low and middle-income countries. We sought to evaluate the rates of and risk factors for LTBI prevalence and LTBI test conversion among HCWs using the tuberculin skin test (TST) and QuantiFERON-TB Gold In-tube assay (QFT-GIT). Methods A prospective longitudinal study was conducted among HCWs in the country of Georgia. Subjects completed a questionnaire, and TST and QFT-GIT tests were performed. LTBI testing was repeated 6-26 months after baseline testing. Results Among 319 HCWs enrolled, 89% reported prior BCG vaccination, and 60% worked in TB healthcare facilities (HCFs). HCWs from TB HCFs had higher prevalence of positive QFT-GIT and TST than those from non-TB HCFs: 107/194 (55%) vs. 30/125 (31%) QFT-GIT positive (p<0.0001) and 128/189 (69%) vs. 64/119 (54%) TST positive (p = 0.01). There was fair agreement between TST and QFT-GIT (kappa = 0.42, 95% CI 0.31–0.52). In multivariate analysis, frequent contact with TB patients was associated with increased risk of positive QFT-GIT (aOR 3.04, 95% CI 1.79–5.14) but not positive TST. Increasing age was associated with increased risk of positive QFT-GIT (aOR 1.05, 95% CI 1.01–1.09) and TST (aOR 1.05, 95% CI 1.01–1.10). High rates of HCW conversion were seen: the QFT-GIT conversion rate was 22.8/100 person-years, and TST conversion rate was 17.1/100 person-years. In multivariate analysis, female HCWs had decreased risk of TST conversion (aOR 0.05, 95% CI 0.01–0.43), and older HCWs had increased risk of QFT-GIT conversion (aOR 1.07 per year, 95% CI 1.01–1.13). Conclusion LTBI prevalence and LTBI test conversion rates were high among Georgian HCWs, especially among those working at TB HCFs. These data highlight the need for increased implementation of TB infection control measures.

Variability in Humoral Immunity to Measles Vaccine: New Developments

Despite the existence of an effective measles vaccine, resurgence in measles cases in the USA and across Europe has occurred, including in individuals vaccinated with two doses of the vaccine. Host genetic factors result in inter-individual variation in measles vaccine-induced antibodies, and play a role in vaccine failure. Studies have identified HLA (human leukocyte antigen) and non-HLA genetic influences that individually or jointly contribute to the observed variability in the humoral response to vaccination among healthy individuals. In this exciting era, new high-dimensional approaches and techniques including vaccinomics, systems biology, GWAS, epitope prediction and sophisticated bioinformatics/statistical algorithms provide powerful tools to investigate immune response mechanisms to the measles vaccine. These might predict, on an individual basis, outcomes of acquired immunity post measles vaccination.

Catheter Salvage After Catheter-Related Bloodstream Infection During Home Parenteral Nutrition.

Background: Catheter-related bloodstream infection (CRBSI) is a common complication in patients receiving home parenteral nutrition (HPN). Data regarding catheter salvage after a CRBSI episode are limited. We aimed to determine the incidence of CRBSI and rates of catheter salvage in adult patients receiving HPN. Materials and Methods: We retrospectively searched our prospectively maintained HPN database for the records of all adult patients receiving HPN from January 1, 1990, to December 31, 2013, at our tertiary referral center. Data abstracted from the medical records included demographics, diseases, treatments, and outcomes. The incidence of CRBSI and rates of catheter salvage were determined. Results: Of 1040 patients identified, 620 (59.6%) were men. The median total duration on HPN was 124.5 days (interquartile range, 49.0–345.5 days). Mean (SD) age at HPN initiation was 53.3 (15.3) years. During the study period, 465 CRBSIs developed in 187 patients (18%). The rate of CRBSI was 0.64/1000 catheter days. Overall, 70% of catheters were salvaged (retained despite CRBSI) during the study period: 78% of infections with coagulase-negative staphylococci, 87% with methicillin-sensitive Staphylococcus aureus, and 27% with methicillin-resistant S aureus. The percentage of catheters salvaged was 63% from 1990 to 1994, 63% from 1995 to 1999, 61% from 2000 to 2004, 72% from 2005 to 2009, and 76% from 2010 to 2013. Conclusion: Catheter salvage is possible after a CRBSI episode. Since most episodes of CRBSI are caused by skin commensals, effective treatment without removal of the central venous catheter is possible in most cases.

Adversomics: a new paradigm for vaccine safety and design

Despite the enormous population benefits of routine vaccination, vaccine adverse events (AEs) and reactions, whether real or perceived, have posed one of the greatest barriers to vaccine acceptance – and thus to infectious disease prevention – worldwide. A truly integrated clinical, translational, and basic science approach is required to understand the mechanisms behind vaccine AEs, predict them, and then apply this knowledge to new vaccine design approaches that decrease, or avoid, these events. The term ‘adversomics’ was first introduced in 2009 and refers to the study of vaccine adverse reactions using immunogenomics and systems biology approaches. In this review, we present the current state of adversomics research, review known associations and mechanisms of vaccine AEs/reactions, and outline a plan for the further development of this emerging research field.

Prevention of Subsequent Catheter-Related Bloodstream Infection Using Catheter Locks in High-Risk Patients Receiving Home Parenteral Nutrition

Introduction:Catheter-related bloodstream infection (CRBSI) is a serious complication in patients receiving home parenteral nutrition (HPN). Antibiotic lock therapy (ALT) and ethanol lock therapy (ELT) can be used to prevent CRBSI episodes in high-risk patients. Methods: Following institutional review board approval, all patients enrolled in the Mayo Clinic HPN program from January 1, 2006, to December 31, 2013, with catheter locking were eligible to be included. Patients without research authorization and <18 years old at the initiation of HPN were excluded. Total number of infections before and after ALT or ELT were estimated in all patients. Results: A total of 63 patients were enrolled during the study period. Of 59 eligible patients, 29 (49%) were female, and 30 (51%) were male. The median duration of HPN was 3.66 (interquartile range, 0.75–8.19) years. The mean age ± SD at initiation of HPN was 49.89 ± 14.07 years. A total of 51 patients were instilled with ALT, and 8 patients were instilled with ELT during their course of HPN. A total of 313 CRBSI episodes occurred in these patients, 264 before locking and 49 after locking (P < .001). Rate of infection per 1000 catheter days was 10.97 ± 25.92 before locking and 1.09 ± 2.53 after locking (P < .001). Discussion: The major findings of the present study reveal that ALT or ELT can reduce the overall rate of infections per 1000 catheter days. ALT or ELT can be used in appropriate clinical setting for patients receiving HPN.

Measles and mumps outbreaks in the United States: Think globally, vaccinate locally

Measles and mumps outbreaks in the United States have laimed numerous headlines over the past six months. The 397 easles cases in the U.S. from January 1 to June 6, 2014 have urpassed the highest annual totals since the 2000 declaration of easles elimination in the U.S. [1]. Mumps outbreaks have made heir marks across college campuses in Ohio and New York. What imilarities have there been in the recent U.S. measles and mumps utbreaks? Both have highlighted the importance of imported nfections to the U.S. among unvaccinated travelers. Both have lluminated “failure to vaccinate” cracks in MMR vaccine coverge in Western Europe and the U.S., which largely have their roots n the anti-vaccine movement and scientifically unfounded conerns about the measles-mumps-rubella (MMR) vaccine. Both have aised questions of vaccine failure. Measles is one of the most contagious viruses known in umans and has a secondary attack rate in susceptible contacts f greater than 90% [2]. Before the advent of the measles vaccine, 00,000 measles cases were reported annually in the U.S., with 500 easles-related deaths, 48,000 hospitalizations, and 4000 cases of ncephalitis leaving nearly 1000 of those patients permanently deaf r with neurologic impairment [3]. Worldwide, it is estimated the easles vaccine saved an estimated 12.7 million lives during the ears of 2000–2008 [3]. Global reductions in measles morbidity and ortality are tremendous public health achievements. Measles is argeted for elimination in five WHO regions by 2020 [4], and WHO as concluded that measles eradication is feasible and a future goal 5]. Despite these advances, large measles outbreaks in countries hat do not lack access to MMR vaccine continue to occur. The nited Kingdom declared measles endemic again in 2008 [6]. The HO European Region reported >30,000 cases of measles in 2011 nd was the source of nearly half of the measles importations to he U.S. in 2011 [7]. Of the 288 measles cases reported from January 1 to May 23, 014, 97% were associated with importations from 18 different ountries [8]. Forty of the 45 importations (89%) were from U.S. esidents returning from abroad [8]. Only five importations were dentified from foreign visitors. Forty-nine percent of the imporations were from the Philippines, with an additional 16% being ssociated with travel to the WHO Western Pacific Region, 18% to HO Southeast Asia, 9% to European, and 8% to Americas regions 8]. The majority (69%) of the 288 cases occurred in unvaccinated ndividuals or those who had unknown MMR vaccination staus (20%). But importantly, 10% of cases occurred in previously

“Let there be light”: the role of vitamin D in the immune response to vaccines

Vitamin D’s non-skeletal actions, including immunomodulatory role, have been increasingly recognized. Of significance, many immune cells are able to synthesize a biologically active form of vitamin D from circulating 25-hydroxyvitamin D with subsequent intracrine actions, and the vitamin D receptor is broadly distributed. In this review, we discuss vitamin D’s potent role in innate and adaptive immune responses and published studies evaluating the impact of serum vitamin D, vitamin D gene pathway polymorphisms or empiric vitamin D supplementation on vaccine immunogenicity. We highlight existing knowledge gaps and propose the steps needed to advance the science and answer the question of whether vitamin D may prove valuable as a vaccine adjuvant for certain vaccines against infectious diseases.

Vaccinology in the third millennium: scientific and social challenges

The epidemiology of deaths due to vaccine-preventable diseases has been significantly and positively altered through the use of vaccines. Despite this, significant challenges remain in vaccine development and use in the third millennium. Both new (Ebola, Chikungunya, Zika, and West Nile) and re-emerging diseases (measles, mumps, and influenza) require the development of new or next-generation vaccines. The global aging of the population, and accumulating numbers of immunocompromised persons, will require new vaccine and adjuvant development to protect large segments of the population. After vaccine development, significant challenges remain globally in the cost and efficient use and acceptance of vaccines by the public. This article raises issues in these two areas and suggests a way forward that will benefit current and future generations.

Determinants of Tuberculosis Infection Control–Related Behaviors Among Healthcare Workers in the Country of Georgia

OBJECTIVE To better understand tuberculosis (TB) infection control (IC) in healthcare facilities (HCFs) in Georgia. DESIGN A cross-sectional evaluation of healthcare worker (HCW) knowledge, beliefs and behaviors toward TB IC measures including latent TB infection (LTBI) screening and treatment of HCWs. SETTING Georgia, a high-burden multidrug-resistant TB (MDR-TB) country. PARTICIPANTS HCWs from the National TB Program and affiliated HCFs. METHODS An anonymous self-administered 55-question survey developed based on the Health Belief Model (HBM) conceptual framework. RESULTS In total, 240 HCWs (48% physicians; 39% nurses) completed the survey. The overall average TB knowledge score was 61%. Only 60% of HCWs reported frequent use of respirators when in contact with TB patients. Only 52% of HCWs were willing to undergo annual LTBI screening; 48% were willing to undergo LTBI treatment. In multivariate analysis, HCWs who worried about acquiring MDR-TB infection (adjusted odds ratio [aOR], 1.7; 95% confidence interval [CI], 1.28-2.25), who thought screening contacts of TB cases is important (aOR, 3.4; 95% CI, 1.35-8.65), and who were physicians (aOR, 1.7; 95% CI, 1.08-2.60) were more likely to accept annual LTBI screening. With regard to LTBI treatment, HCWs who worked in an outpatient TB facility (aOR, 0.3; 95% CI, 0.11-0.58) or perceived a high personal risk of TB reinfection (aOR, 0.5; 95% CI, 0.37-0.64) were less likely to accept LTBI treatment. CONCLUSION The concern about TB reinfection is a major barrier to HCW acceptance of LTBI treatment. TB IC measures must be strengthened in parallel with or prior to the introduction of LTBI screening and treatment of HCWs.