Racial–ethnic differences in Epstein–Barr virus antibody titers among U.S. children and adolescents

PurposeTo examine racial–ethnic differences in Epstein–Barr virus (EBV) antibody levels among U.S. children and adolescents. Elevated titers among seropositive youth can indicate viral reactivation—an indirect measure of impaired cell-mediated immunity.MethodsData from the 2003–2010 National Health and Nutrition Examination Survey were analyzed using multivariable linear regression accounting for the complex survey design and potential confounders. The sample comprised 4663 black-African American, Mexican American, and white youth aged 6–17 years who were EBV seropositive.ResultsEBV antibody levels were significantly higher for black-African American youth compared with their white peers (b = 0.343, P < .0001). Gender-stratified models were consistent with the total sample except differences in EBV antibody levels were greater between black-African American and white males (b = 0.525, P < .0001) than between black-African American and white females (b = 0.169, P = .0185). Differences in EBV antibody levels between Mexican American and white youth were only marginally significant in the total and the gender-stratified samples.ConclusionsBlack–white differences in EBV antibody levels were found suggesting EBV reactivation and potential disparities in immune function among minority youth. Research on multilevel factors contributing to the disparities is needed, including potential health implications over the life course for minority youth.     

Seroepidemiology of Epstein−Barr virus and cytomegalovirus among Israeli male young adults

PurposeTo assess the seroprevalence and seroconversion of Epstein?Barr virus (EBV) and cytomegalovirus (CMV) Immunoglobulin G (IgG) antibodies and identify associated socioeconomic and smoking variables among male young adults in Israel, to explore health disparities and aid prevention efforts.MethodsA population-based seroprevalence study of EBV and CMV IgG antibodies in a systematic sample of Israeli males upon recruitment to mandatory military service during 1994–2004. Associations between socioeconomic and smoking variables and the seroprevalence of EBV/CMV were evaluated, controlling for possible confounders. A subset of seronegative subjects was assessed for seroconversion upon discharge from military service.ResultsOverall seroprevalence rates were 87% for EBV and 59% for CMV. An association between the seroprevalence of EBV and CMV was observed. Seroconversion was 56% for EBV as compared with 31% for CMV. Lower paternal education was found to be associated with both EBV and CMV seroprevalence. Lower socioeconomic status, North African origin, and urban residence were found to be associated with CMV seropositivity, as was smoking for EBV seropositivity.ConclusionsSocioeconomic disparities exist in the seroprevalence rates of CMV and EBV among Israeli male young adults. The results of the study could aid public health efforts and determine target populations when a vaccine becomes available.     

Effectiveness of a novel herbal agent MB-6 as a potential adjunct to 5-fluoracil–based chemotherapy in colorectal cancer

Natural products, such as fermented soybeans, have been used to treat various physical conditions, including cancer. MB-6 is a botanical preparation composed of fermented soybean extract, green tea extract, Antrodia camphorata mycelia, spirulina, grape seed extract, and curcumin extract. Based on this, we hypothesized that MB-6 would increase the effectiveness of chemotherapy in patients with colon cancer. In a rodent study, MB-6, in combination with leucovorin/5-fluorouracil chemotherapy, increased the survival rate and life span of colon cancer tumor-bearing BALB/c mice as compared with treatment with chemotherapy alone. In a proof-of-concept clinical study, 72 patients with metastatic colorectal cancer were randomized to receive leucovorin, 5-fluorouracil, and oxaliplatin in combination with either MB-6 or placebo for 16 weeks. The primary outcome was the best overall response, and secondary outcomes included progression-free survival, overall survival, and adverse effects. Up to 77 weeks after treatment, there was follow-up with the patients. No significant difference in the best overall response rate and overall survival was observed between the 2 groups. Patients in the MB-6 group had a significantly lower disease progression rate than patients in the placebo group, during the study period (0.0% vs 15.8%, P = .026). The placebo group had a significantly higher incidence of adverse events at least grade 4 compared with the MB-6 group (28.9% vs 2.9%, respectively, P = .004) and a significantly higher occurrence of increased serum creatinine compared with the MB-6 group (29% vs 5.9%, P = .014). MB-6 is a promising botanical supplement that may increase the effectiveness of chemotherapy in patients with metastatic colorectal cancer.     

Synthesis of novel α-santonin derivatives as potential cytotoxic agents

Ten novel α-santonin derivatives have been synthesized as cytotoxic agents. The in vitro antitumor activity of these compounds has been evaluated against cancer cells lines. Structure-activity relationships indicate that α-methylene-γ-lactone and endoperoxide functionalities play important roles in conferring cytotoxicity. The compounds 2-4, possessing the α-methylene-γ-lactone group showed IC50 values between 5.70 and 16.40 μM. Mixture of isomers 5 and 6, with the α-methylene-γ-lactone and endoperoxide functionalities, displayed the greatest activity, with IC50 values between 1.45 and 4.35 μM. The biological assays conducted with normal cells revealed that the compounds 2, 5 and 6 are selective against cancer cells lines tested. Bioactive lactones described herein and in our previous report did not cause disruption of the cell membrane in mouse erythrocytes.     

Rabies virus vaccines: Is there a need for a pan-lyssavirus vaccine?

All members of the lyssavirus genus are capable of causing disease that invariably results in death following the development of clinical symptoms. The recent detection of several novel lyssavirus species across the globe, in different animal species, has demonstrated that the lyssavirus genus contains a greater degree of genetic and antigenic variation than previously suspected. The divergence of species within the genus has led to a differentiation of lyssavirus isolates based on both antigenic and genetic data into two, and potentially a third phylogroup. Critically, from both a human and animal health perspective, current rabies vaccines appear able to protect against lyssaviruses classified within phylogroup I. However no protection is afforded against phylogroup II viruses or other more divergent viruses. Here we review current knowledge regarding the diversity and antigenicity of the lyssavirus glycoprotein. We review the degree of cross protection afforded by rabies vaccines, the genetic and antigenic divergence of the lyssaviruses and potential mechanisms for the development of novel lyssavirus vaccines for use in areas where divergent lyssaviruses are known to circulate, as well as for use by those at occupational risk from these pathogens.     

Genetic variation and evolution of foot–and–mouth disease virus serotype A in relation to vaccine matching

Foot–and–mouth disease (FMD) is a severe, highly contagious viral disease that affects a wide variety of domestic and wild cloven-hoofed animals. FMD vaccines can play a vital role in disease control and are very widely used globally each year. However, due to the diversity of FMDV, the choice of FMD vaccine is still a huge challenge. In this study, 45 FMDV/A isolates were phylogenetically categorized into three topotypes: ASIA (n = 31), AFRICA (n = 10), and EURO–SA (n = 4). Three sera collected from vaccinated cattle with FMDV A22/IRQ/24/64, A/IRN/05, and A/ARG/01 were used to evaluate their antigenic relationship (r₁) with the field isolates. The IRQ/24/64 serum demonstrated a 39% (17/44) match (r₁ ≥ 0.3) to the field isolates, whereas IRN/05 serum and ARG/01serum showed an 18% (8/44) and a 2% (1/44) match (r₁ ≥ 0.3) to the field isolates, respectively. The A22/IRQ/24/64 matched with isolates mainly from topotype ASIA, with limited cross–topotype match with isolates from topotypes AFRICA and EURO–SA. However, the A/IRN/05 did not show a cross–topotype match with topotype AFRICA isolates and A/ARG/01 failed to match any isolates from topotypes ASIA and AFRICA. After analyzing the amino acid variation of the known antigenic sites of 45 strains of FMDV/A, it was found that together antigenic sites 1 and 3 contributed about 71% of the amino acid changes to the vaccine evaluated. Based on the capsid sequences, the FMDV/A evolved unequally among topotypes. The topotypes of ASIA and AFRICA evolves faster than that of EURO–SA. The FMDV/A continues to show a high level of genetic diversity driven by a high substitution rate, purifying selection, and positive selection concentrated on antigenic sites or near antigenic sites. The current research shows the challenges of the FMDV/A vaccine selection and emphasizes the importance of continuous monitoring of antigenic evolution for the selection of effective vaccines.     

Cost-effectiveness of a potential vaccine candidate for Haemophilus influenzae serotype ‘a’

The preceding decade has witnessed the emergence of severe community-acquired acute infections caused by Haemophilus influenzae serotype a (Hia), with alarming incidence rates in North America, particularly among indigenous populations. The remarkable success of Hib conjugate vaccine over the past 20 years signify the development of an Hia vaccine candidate as a prevention measure to reduce the incidence of invasive Hia disease. However, quantifications of the long-term epidemiologic and economic impacts of vaccination are needed to inform decision on investment in Hia vaccine development and immunization programs. We sought to evaluate the cost-effectiveness of an Hia vaccine with a similar routine infant immunization schedules currently in practice for Hib in Canada. We developed and parameterized an agent-based simulation model using age-specific incidence rates reported for Nunavut, a Canadian territory with predominantly aboriginal populations. Our results, based on statistical analyses of the incremental cost-effectiveness ratio, show that an Hia conjugate vaccine is highly cost-effective. Sustaining an immunization program with vaccine coverages of 77% for primary series and 93% for booster dose over a 10-year period reduces the incidence of invasive disease by 63.8% on average from 9.97 to 3.61 cases, per 100,000 population. The overall costs of disease management in year 10 are reduced by 53.4% from CDN $1.863 million (95% CI: $1.229–$2.519 M) to CDN $0.868 million (95% CI: $0.627–$1.120 M). The findings suggest an important role for a conjugate vaccine in managing Hia disease as a growing public health threat.     

Relationship between Guillain–Barré syndrome,influenza-related hospitalizations,and influenza vaccine coverage

Some studies reported an increased risk of Guillain–Barré syndrome (GBS) within six weeks of influenza vaccination. It has also been suggested that this finding could have been confounded by influenza illnesses. We explored the complex relationship between influenza illness, influenza vaccination, and GBS, from an ecologic perspective using nationally representative data. We also studied seasonal patterns for GBS hospitalizations.Monthly hospitalization data (2000–2009) for GBS, and pneumonia and influenza (P&I) in the Nationwide Inpatient Sample were included. Seasonal influenza vaccination coverage for 2004–2005 through the 2008–2009 influenza seasons (August–May) was estimated from the National Health Interview Survey data. GBS seasonality was determined using Poisson regression. GBS and P&I temporal clusters were identified using scan statistics. The association between P&I and GBS hospitalizations in the same month (concurrent) or in the following month (lagged) were determined using negative binomial regression.Vaccine coverage increased over the years (from 19.7% during 2004–2005 to 35.5% during 2008–2009 season) but GBS hospitalization did not follow a similar pattern. Overall, a significant correlation between monthly P&I and GBS hospitalizations was observed (Spearman's correlation coefficient = 0.7016, p < 0.0001). A significant (p = 0.001) cluster of P&I hospitalizations during December 2004–March 2005 overlapped a significant (p = 0.001) cluster of GBS hospitalizations during January 2005–February 2005. After accounting for effects of monthly vaccine coverage and age, P&I hospitalization was significantly associated (p < 0.0001) with GBS hospitalization in the concurrent month but not with GBS hospitalization in the following month. Monthly vaccine coverage was not associated with GBS hospitalization in adjusted models (both concurrent and lagged). GBS hospitalizations demonstrated a seasonal pattern with winter months having higher rates compared to the month of June.P&I hospitalization rates were significantly correlated with hospitalization rates for GBS. Vaccine coverage did not significantly affect the rates of GBS hospitalization at the population level.     

Safety and immunogenicity of a measles–mumps–rubella–varicella vaccine given as a second dose in children up to six years of age

Two doses of measles–mumps–rubella vaccine (MMR) are widely recommended and consideration is being given to a similar schedule for varicella vaccine. A combined measles–mumps–rubella–varicella vaccine (MMRV) could be considered for this second dose in children previously vaccinated separately with MMR and varicella vaccines. Healthy children (N = 390) aged 15–75 months (median 54 months) previously immunized with MMR and varicella vaccines were randomly allocated to receive MMRV or separate injections of MMR and varicella vaccines. Before administration of study vaccines, seropositivity rates were 96.4% for measles, 94.3% for mumps, 99.5% for rubella, and 97.9% for varicella. Post-immunization, seropositivity rates were 99.5% for measles and mumps and 100% for rubella and varicella in the MMR + varicella group and 100% for all four antigens in the MMRV group; a 26.2- and 27.2-fold increase in varicella titer was observed in the MMR + varicella vaccine and MMRV groups, respectively. Except for more frequent pain in the MMRV group (33.3% vs. 23.7%, p = 0.043), there were no differences in the incidence of local and solicited symptoms between groups. In children primed with MMR and varicella vaccine, MMRV had non-inferior immunogenicity and similar safety profiles as a second dose of licensed MMR and varicella vaccine administered concomitantly.     

Does a major change to a COVID-19 vaccine program alter vaccine intention? A qualitative investigation

BackgroundOn 8th April 2021, the Australian Technical Advisory Group on Immunisation (ATAGI) made the Pfizer-BioNtech (Comirnaty) vaccine the “preferred” vaccine for adults in Australia aged < 50 years due to a risk of thrombosis with thrombocytopenia syndrome (TTS) following AstraZeneca vaccination. We sought to understand whether this impacted COVID-19 vaccine intentions.MethodWe undertook qualitative interviews from February – April 2021 before and after the program change with 28 adults in Perth, Western Australia. Using our COVID-19 vaccine intentions model, we assessed changes in participants’ COVID-19 vaccine intention before and after the program change. Participants were classified as 1) ‘acceptors’: no concerns about COVID-19 vaccine safety, efficacy, access and would accept whatever vaccine is offered, 2) ‘cautious acceptors’: some concerns and would prefer a particular vaccine brand but would accept whatever is offered, 3) ‘Wait awhile’: for more data, easier access, for another vaccine brand, a greater perceived COVID-19 threat or until mandatory, or 4) ‘refuser’: no intention to vaccinate due to concerns about safety and/or efficacy.ResultsBefore the change, 7/18 of those aged < 50 years were ‘acceptors,’ 10/18 were ‘cautious acceptors’ and 1/18 was ‘wait awhile.’ Overall, 14/18 participants had the same COVID-19 vaccine intention after the change; 4/18 became more concerned. For those aged ≥ 50 years and before the change, 5/10 were ‘acceptors’ and 5/10 were ‘cautious acceptors.’ After the change, 8/10 still had the same COVID-19 vaccine intention; 2/10 became more cautious. The major concern before the program change was COVID-19 vaccines having different vaccine efficacy; the concern pivoted to safety.ConclusionThe majority of participants were ‘cautious acceptors’ who intended on being vaccinated; many had this intention before and after the program change. The Australian government, health care providers and media need to better address COVID-19 vaccine concerns to assist those with COVID-19 vaccine intentions receive a vaccine.     

A β-glucan-conjugate vaccine and anti-β-glucan antibodies are effective against murine vaginal candidiasis as assessed by a novel in vivo imaging technique

The protective capacity of a parenterally administered β-glucan-conjugate vaccine formulated with the human-compatible MF59 adjuvant was assessed in a murine model of vaginal candidiasis. To monitor infection, an in vivo imaging technique exploiting genetically engineered, luminescent Candida albicans was adopted, and compared with measurements of colony forming units. The vaccine conferred significant protection, and this was associated with production of serum and vaginal anti-β-glucan IgG antibodies. Vaginal IgG molecules were the likely mediators of protection as inferred by the efficacy of passive transfer of immune vaginal fluid and passive protection by an anti-β-1,3-glucan mAb. Overall, the in vivo imaging technique was more reliable than vaginal CFU counts in assessing the extent and duration of the vaginal infection, and the consequent protection level.     

Examination of universal purchase programs as a driver of vaccine uptake among US States, 1995–2014

BackgroundImmunization against numerous potentially life-threatening illnesses has been a great public health achievement. In the United States, the Vaccines for Children (VFC) program has provided vaccines to uninsured and underinsured children since the early 1990s, increasing vaccination rates. In recent years, some states have adopted Universal Purchase (UP) programs with the stated aim of further increasing vaccination rates. Under UP programs, states also purchase vaccines for privately-insured children at federally-contracted VFC prices and bill private health insurers for the vaccines through assessments.MethodsIn this study, we estimated the effect of UP adoption in a state on children’s vaccination rates using state-level and individual-level data from the 1995–2014 National Immunization Survey. For the state-level analysis, we performed ordinary least squares regression to estimate the state’s vaccination rate as a function of whether the state had UP in the given year, state demographic characteristics, other vaccination policies, state fixed effects, and a time trend. For the individual analysis, we performed logistic regression to estimate a child’s likelihood of being vaccinated as a function of whether the state had UP in the given year, the child’s demographic characteristics, state characteristics and vaccine policies, state fixed effects, and a time trend. We performed separate regressions for each of nine recommended vaccines, as well as composite measures on whether a child was up-to-date on all required vaccines.ResultsIn the both the state-level and individual-level analyses, we found UP had no significant (p < 0.10) effect on any of the vaccines or composite measures in our base case specifications. Results were similar in alternative specifications.ConclusionsWe hypothesize that UP was ineffective in increasing vaccination rates. Policymakers seeking to increase vaccination rates would do well to consider other policies such as addressing provider practice issues and vaccine hesitancy.     

Coexisting infectious diseases on admission as a risk factor for mechanical ventilation in patients with Guillain–Barré syndrome

Background

The aim of this study was to investigate patient characteristics on admission to hospital that increase the risk of subsequent mechanical ventilation (MV) use for patients with Guillain–Barré syndrome (GBS).

A cost–effectiveness analysis of Japanese encephalitis vaccine in Cambodia

This study aimed to evaluate the cost and effectiveness of introducing a live, attenuated vaccine (SA 14-14-2) against Japanese encephalitis (JE) into the immunization program. The study demonstrated that SA 14-14-2 immunization is cost–effective in controlling JE in Cambodia compared to no vaccination. Averting one disability-adjusted life year, from a societal perspective, through the introduction of SA 14-14-2 through routine immunization, or a combination of routine immunization plus a campaign targeting children 1–5 or 1–10 years of age, costs US$22, US$34 and US$53, respectively. Sensitivity analyses confirmed that there was a high probability of SA 14-14-2 immunization being cost–effective under conditions of uncertainty.     

Influenza B virus reverse genetic backbones with improved growth properties in the EB66® cell line as basis for vaccine seed virus generation

Vaccination remains the best available prophylaxis to prevent influenza virus infections, yet current inadequacies in influenza virus vaccine manufacturing often lead to vaccine shortages at times when the vaccine is most needed, as it was the case during the last influenza virus pandemic. Novel influenza virus vaccine production systems will be crucial to improve public health and safety. Here we report the optimization of influenza B virus growth in the proprietary EB66® cell line, currently in use for human vaccine production. To this end, we collected, curated and sequenced 71 influenza B viruses selected for high diversity in date of isolation and lineage. This viral collection was tested for ability to enter and replicate within EB66® cells in a single cycle assay and appears to readily infect these cells. When the collection was tested for viral progeny production in a multi-cycle assay, we found a large variation from strain to strain. The strains with the top growth characteristics from the B/Victoria and B/Yamagata lineages were selected for vaccine backbone generation using a reverse genetics system. We then showed that these backbones maintain their desirable growth within EB66® cells when the HA and NA from poorly growing strains were substituted for the parental segments, indicating that the selected backbones are viable options for vaccine production in EB66®. Finally, we show that compounds previously reported to enhance influenza virus growth in cell culture also increase virus production in the EB66® cell line.