Predicting Efficacy of a Purified Inactivated Zika Virus Vaccine in Flavivirus-Naïve Humans Using an Immunological Correlate of Protection in Non-Human Primates.

A traditional phase 3 clinical efficacy study for a Zika vaccine may be unfeasible because of the current low transmission of Zika virus (ZIKV). An alternative clinical development approach to evaluate Zika vaccine efficacy (VE) is therefore required, delineated in the US FDA's Accelerated Approval Program for licensure, which utilizes an anti-Zika neutralizing antibody (Zika NAb) titer correlated with non-human primate (NHP) protection as a surrogate endpoint. In this accelerated approval approach, the estimation of VE would be inferred from the percentage of phase 3 trial participants achieving the established surrogate endpoint. We provide a statistical framework to predict the probability of protection for human participants vaccinated with a purified inactivated ZIKV vaccine (TAK-426), in the absence of VE measurements, using NHP data under a single-correlate model. Based on a logistic regression (LR) with bias-reduction model, a probability of 90% protection in humans is expected with a ZIKV NAb geometric mean titer (GMT) ≥ 3.38 log10 half-maximal effective concentration (EC50). The predicted probability of protection of TAK-426 against ZIKV infection was determined using the two-parameter LR model that fit the calculated VE in rhesus macaques and the flavivirus-naïve phase 1 trial participants' ZIKV NAb GMTs log10 EC50, measured by a ZIKV reporter virus particle assay, at 1 month post dose 2. The TAK-426 10 µg dose predicted a probability of protection from infection of 98% among flavivirus-naïve phase 1 trial participants.

Potential distribution and spread of Japanese beetle in Washington State.

The Japanese beetle, Popillia japonica (Newman, 1841) (Coleoptera: Scarabaeidae), was first detected in southern Washington State in 2020. Widespread trapping efforts ensued, and over 23,000 individuals were collected in both 2021 and 2022 in this region known for specialty crop production. The invasion of Japanese beetle is of major concern as it feeds on over 300 plant species and has shown an ability to spread across landscapes. Here, we created a habitat suitability model for Japanese beetle in Washington and used dispersal models to forecast invasion scenarios. Our models predict that the area of current establishment occurs in a region with highly suitable habitat. Moreover, vast areas of habitat that are likely highly suitable for Japanese beetle occur in coastal areas of western Washington, with medium to highly suitable habitat in central and eastern Washington. Dispersal models suggested that the beetle could spread throughout Washington within 20 years without management, which justifies quarantine and eradication measures. Timely map-based predictions can be useful tools to guide management of invasive species while also increasing citizen engagement to invaders.

Persistence of Immunogenicity of a Purified Inactivated Zika Virus Vaccine Candidate in Healthy Adults: 2 Years of Follow-up Compared With Natural Infection.

BACKGROUND: We report 2-year persistence of immune response to Takeda's prophylactic purified formalin-inactivated whole Zika virus vaccine candidate (TAK-426) compared with that observed after natural infection. METHODS: A randomized, observer-blind, placebo-controlled, dose-selection, phase 1 trial was conducted in 18-49-year-old adults at 9 centers (7 in the United States, 2 in Puerto Rico) from 13 November 2017 to 24 November 2020. Primary objectives were safety, tolerability, and immunogenicity of 3 increasing doses of TAK-426 administered as 2 doses 28 days apart to flavivirus (FV)-naive and FV-primed adults. Here, we report on safety and persistence of immunity up to 2 years after primary vaccination with 10-µg TAK-426, the highest dose, and compare neutralizing antibody responses with those observed after natural infection. RESULTS: TAK-426 at 10-µg had an acceptable safety profile in FV-naive and FV-primed adults up to 24 months after dose 2. Seropositivity for neutralizing antibodies was 100% at 1 year, and 93.8% and 76.2% at 2 years in FV-naive and FV-primed groups, respectively. TAK-426 responses were comparable in magnitude and kinetics with those elicited by natural Zika virus infection. CONCLUSIONS: These results support the further clinical development of TAK-426 for both FV-naive and FV-primed populations. CLINICAL TRIALS REGISTRATION: NCT03343626.

Trichoderma koningiopsis Survival on Coated Seeds and Effect on Plant Growth Promotion in Rice (Oryza sativa).

Seed coating is an alternative delivery system for beneficial plant microorganisms into the soil. Although seed coats are widely used for the application of agrochemicals, the incorporation of beneficial microorganisms has not been explored deeply and their survival on seeds while in storage is unknown. The study aimed to evaluate the effect of the coating process on microbial survival and on plant growth promotion. Two coating formulations were designed, and assessed by two coating processes: rotating drum and fluidized bed. The rotating drum process resulted in more uniform coatings than in the fluidized bed process. In addition, with this coating technique, lower viability losses over time were observed. The rotatory drum prototype containing a biopolymer and a clay mineral derivate (P90) showed the best behavior at the three temperatures evaluated, with superior viabilities compared to the other prototypes and the lowest loss of viability after 12 months. The formulation of this coating prototype may preserve the viability of Trichoderma koningiopsis Th003 up to 15 months at 8 °C, 9 months at 18 °C, and 3 months at 28 °C, which are very promising shelf-life results. Regarding the effect of seed coating on plant growth, prototypes showed higher yields > 16% than the control, comparable to the conventional use of Tricotec® WG, which may reduce the number of applications and water consumption for dissolution of the inoculant. The results demonstrated that the formulation composition, as well as the coating process may impact the microbial survival on seeds.

Safety and immunogenicity of a purified inactivated Zika virus vaccine candidate in healthy adults: an observer-blind, randomised, phase 1 trial.

BACKGROUND: Zika virus, a flavivirus transmitted by Aedes aegypti and Aedes albopictus mosquitoes, is associated with cases of congenital malformations and neurological complications. Absence of specific treatment makes a prophylactic Zika virus vaccine an unmet medical need. We assessed safety and immunogenicity of three doses of a purified, inactivated, Zika virus vaccine candidate in healthy flavivirus-naive and flavivirus-primed adults. METHODS: This two-part, multicentre, observer-blind, randomised, placebo-controlled, phase 1 trial was done at seven medical clinics in the USA and two in Puerto Rico. Eligible participants were healthy adults aged 18-49 years. Participants were randomly assigned (1:1:1:1), using a sponsor-supplied randomisation scheme, to four groups to receive two intramuscular injections, 28 days apart, of saline placebo or TAK-426 containing 2 µg, 5 µg, or 10 µg antigen. Participants, investigators, and vaccine administrating personnel were masked to group assignment. Part 1 of the study assessed flavivirus-naive participants and part 2 assessed flavivirus-primed participants. The primary outcomes were safety, tolerability, and immunogenicity based on solicited local reactions and solicited systemic adverse events in the 7 days after each dose; unsolicited adverse events and serious adverse events in the 28 days after each dose; and geometric mean titres (GMTs) of neutralising anti-Zika virus antibodies at 28 days after the second dose. Safety assessments were done in all participants who received at least one dose of vaccine. Immunogenicity assessments were in the per-protocol set, comprising all participants who received at least one dose of vaccine and provided valid serology results at baseline and at least one post-vaccination timepoint, with no major protocol violations. The trial is ongoing and is registered at ClinicalTrials.gov (NCT03343626). FINDINGS: Between Nov 13, 2017, and Oct 24, 2018, 894 volunteers were screened and 271 enrolled (125 flavivirus-naive and 146 flavivirus-primed participants). All TAK-426 doses were well tolerated with no deaths, no vaccine-related serious adverse events, and similar rates of mainly mild to moderate adverse events. TAK-426 elicited dose-dependent increases in antibody GMTs in both flavivirus-naive and flavivirus-primed participants. 28 days after dose 2, plaque-reduction neutralisation test GMTs in flavivirus-naive participants were 1130 (95% CI 749-1703) in the 2 µg TAK-426 group, 1992 (1401-2833) in the 5 µg TAK-426 group, and 3690 (2677-5086) in the 10 µg TAK-426 group. In pairwise comparisons, responses after two vaccinations in the 10 µg group were significantly greater than in the 2 µg group (GMT ratio 3·27 [95% CI 1·98-5·39], p<0·0001) and the 5 µg group (GMT ratio 1·85 [1·15-2·98], p=0·012). INTERPRETATION: TAK-426 was well tolerated, with an acceptable safety profile, and was immunogenic in both flavivirus-naive and flavivirus-primed adults. Based on the safety and immunogenicity profiles of all TAK-426 doses assessed, the 10 µg TAK-426 dose was selected for further clinical development. FUNDING: Takeda Vaccines and the US Biomedical Advanced Research and Development Authority. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Evaluating the impact of frailty on periprocedural adverse events and mortality among patients with GI bleeding.

BACKGROUND AND AIMS: Frailty is a known predictor of mortality and adverse events in the inpatient setting; however, it has not been studied as a modality to assess risk among patients undergoing endoscopy for GI bleeding (GIB). We aimed to determine the association between frailty status and risk of adverse events in hospitalized patients with GIB who underwent endoscopy. METHODS: We performed a cohort study using the 2016 and 2017 National Inpatient Sample database, using International Classification of Diseases diagnostic codes to identify adult patients with GIB who underwent endoscopic procedures within 2 days of admission and the Hospital Frailty Risk Score to classify patients as frail or nonfrail. Univariable and multivariable logistic regression models were constructed to assess the predictors of periprocedural adverse events, and marginal standardization analysis was performed to assess for possible interaction between age and frailty. RESULTS: A total of 757,920 patients met inclusion criteria, of which 44.4% (336,895) were identified as frail and 55.6% (421,025) as nonfrail; 49.2% of frail patients had composite periprocedural adverse events compared with 25.5% of nonfrail patients (P < .001). Frail patients notably had more cardiovascular (32.1% vs 17.1%, P < .001), pulmonary (18.5% vs 4.3%, P < .001), GI (10.1% vs 6.1%, P < .001), and infectious (9.9% vs .7%, P < .001) adverse events compared with nonfrail patients. Frail patients also had higher all-cause inpatient mortality rates (4.8% vs .5%, P < .001). On multivariable analysis, positive frailty status was associated with a 2.13 times increased likelihood of having composite periprocedural adverse events. CONCLUSIONS: In hospitalized patients undergoing endoscopy for GIB, frailty status is associated with increased periprocedural adverse events including all-cause mortality. The use of frailty assessments can thus further guide clinical decision-making when considering endoscopy and risk of adverse events in adult patients with GI hemorrhage.

Seed coating as a delivery system for the endophyte Trichoderma koningiopsis Th003 in rice (Oryza sativa).

Seed coating is a technique to cover seeds with external agents to upgrade their performance, handling, and plant establishment. Plant beneficial microbes (PBMs), such as plant growth-promoting bacteria, mycorrhizal fungi, and other fungi (e.g., Trichoderma spp.), decrease agrochemical inputs, enhance tolerance to biotic-abiotic stresses, and increase essential plant nutrition. The demand for pre-treated seeds as delivery systems for biological agents is advancing. Here, a seed coating formulation containing Trichoderma koningiopsis is presented. The physicochemical and biological characterization of the seed coating prototypes included drying protector screening, the effect of the inoculum concentration on survival, the assessment of microbial release profiles in soil extract, and plant tissue colonization capability under semi-controlled conditions. Gelatine and pectin, two of the tested drying protectors, maintained fungus germination after 60 days at 18 °C with significantly higher values of up to 38% compared with the control. The initial concentration of 106 colony-forming units (CFU) per seed undergoes a positive effect on survival over time. Regarding plant tissue colonization, the fungus establishes endophytically in rice. In conclusion, seed coating is a promising alternative for the formulation of beneficial microbial agents such as Trichoderma sp., maintaining cell survival and further promoting the establishment in rice systems.Key points• Enhancing drying survival of T. koningiopsis formulates• Seed coating formulation approach for T. koningiopsis in rice• Colonization capacity of formulated T. koningiopsis in rice tissue.

A Phase II Trial of Safety, Tolerability and Immunogenicity of V114, a 15-Valent Pneumococcal Conjugate Vaccine, Compared With 13-Valent Pneumococcal Conjugate Vaccine in Healthy Infants.

BACKGROUND: Pneumococcal disease remains a public health priority worldwide. This phase 2 study (V114-008; NCT02987972; EudraCT 2016-001117-25) compared safety and immunogenicity of 2 clinical lots of V114 (investigational 15-valent pneumococcal vaccine: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19F, 19A, 22F*, 23F, 33F*) to 13-valent pneumococcal conjugate vaccine (PCV13) in healthy infants (*serotypes unique to V114). METHODS: Healthy infants 6-12 weeks old were randomized to receive a 4-dose regimen of V114 Lot 1, V114 Lot 2 or PCV13 at 2, 4, 6 and 12-15 months old. Adverse events were evaluated after each dose. Primary immunogenicity endpoint was to demonstrate noninferiority of V114 Lot 1 and V114 Lot 2 relative to PCV13 based on proportion of infants achieving serotype-specific IgG concentration ≥0.35 µg/mL for 13 serotypes shared with PCV13 at 1 month postdose 3 (PD3). Serotype-specific IgG geometric mean concentrations (GMCs) for all 15 V114 serotypes were measured at PD3, predose 4 and 1 month postdose 4 (PD4). RESULTS: Overall, 1044 of 1051 randomized infants received ≥1 dose of vaccine (V114 Lot 1 [n = 350], V114 Lot 2 [n = 347] or PCV13 [n = 347]). Adverse events were generally comparable across groups. At PD3, both V114 lots met noninferiority criteria for all 13 serotypes shared with PCV13. IgG GMCs were comparable among V114 and PCV13 recipients at PD3 and PD4. Serotype 3 responses were higher following receipt of V114 than PCV13. Both V114 lots induced higher GMCs than PCV13 to the 2 unique V114 serotypes. CONCLUSIONS: Immunogenicity of both V114 lots was noninferior to PCV13 for all 13 shared serotypes between the 2 vaccines and displayed comparable safety and tolerability profiles to PCV13.

Hepatitis B and pertussis antibodies in 4- to 5-year-old children previously vaccinated with different hexavalent vaccines.

In randomized active-comparator controlled studies, DTaP5-HB-IPV-Hib showed comparable immunogenicity and safety to other licensed vaccines. This study assessed persistence of anti-hepatitis B surface antigen (HBs) and anti-pertussis antibodies, when children were 4 to 5 years of age, 3 to 4 years after initial infant/toddler hexavalent vaccination. This was an extension of 2 European studies in which infants/toddlers received either DTaP5-HB-IPV-Hib or DTaP3-HB-IPV/Hib on a 2 + 1 or 3 + 1 schedule. Primary endpoints included percentages with anti-HBs ≥10 mIU/mL, and anti-pertussis toxin (PT), anti-filamentous hemagglutinin (FHA), anti-pertactin (PRN), and anti-fimbriae types 2 & 3 (FIM) greater than or equal to the lower limit of quantitation (LLOQ). One month after 2 + 1 or 3 + 1 dosing, nearly all toddlers had anti-HBs ≥10 mIU/mL, and responded to the received pertussis antigens. Approximately 3 to 4 years later, 65.8%-70.2% in the DTaP5-HB-IPV-Hib and 82.0%-83.7% in the DTaP3-HB-IPV/Hib groups, respectively, had anti-HBs ≥10 mIU/mL. Percentages of children with pertussis antibodies above LLOQ after 2 + 1 dosing were 58.4% and 41.5% (anti-PT), 80.9% and 88.3% (anti-FHA), 66.1% and 72.6% (anti-PRN), and 94.4% and 3.3% (anti-FIM), in the DTaP5-HB-IPV-Hib and DTaP3-HB-IPV/Hib groups, respectively. This study demonstrated, as expected, waning of hepatitis B and pertussis antibodies during the 3 to 4 years after completion of a 3 + 1 or 2 + 1 hexavalent vaccination schedule. Nonetheless, anti-HBs levels ≥10 IU/mL and detectable antibodies against acellular pertussis antigens persisted in most study participants. The implications of these findings for the long-term prevention of hepatitis B and pertussis are further discussed.

Correction to: Public health impact and cost effectiveness of routine childhood vaccination for hepatitis a in Jordan: a dynamic model approach.

Following publication of the original article1, the authors noted the following.

Amelioration of the nigrostriatal pathway facilitated by ultrasound-mediated neurotrophic delivery in early Parkinson's disease.

The blood-brain barrier (BBB) prevents most drugs from gaining access to the brain parenchyma, which is a recognized impediment to the treatment of neurodegenerative disorders like Parkinson's disease (PD). Focused ultrasound (FUS), in conjunction with systemically administered microbubbles, opens the BBB locally, reversibly and non-invasively. Herein, we show that neither FUS applied over both the striatum and the ventral midbrain, without neurotrophic factors, nor intravenous administration of neurotrophic factors (either through protein or gene delivery) without FUS, ameliorates the damage to the nigrostriatal dopaminergic pathway in the sub-acute MPTP mouse model of early-stage PD. Conversely, the combination of FUS and intravenous neurotrophic (protein or gene) delivery attenuates the damage to the nigrostriatal dopaminergic pathway, by allowing the entry of these agents into the brain parenchyma. Our findings provide evidence that the application of FUS at the early stages of PD facilitates critical neurotrophic delivery that can curb the rapid progression of neurodegeneration while improving the neuronal function, seemingly opening new therapeutic avenues for the early treatment of diseases of the central nervous system.

Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine (PCV-15) compared to PCV-13 in healthy older adults.

BACKGROUND: Pneumococcal disease remains a public health priority in adults. Safety and immunogenicity of 2 different formulations of 15-valent pneumococcal conjugate vaccine (PCV15) containing 13 serotypes included in 13-valent pneumococcal conjugate vaccine (PCV13) plus 2 additional serotypes (22F and 33F) were evaluated in adults ≥ 50 years (V114-006; NCT02547649). METHODS: A total of 690 subjects (230/arm) received a single dose of either PCV15 Formulation A, PCV15 Formulation B, or PCV13 and were followed for safety for 14 days postvaccination. Serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) and Immunoglobulin G (IgG) geometric mean concentrations (GMCs) were measured immediately prior and 30 days postvaccination. RESULTS: Both PCV15 formulations had generally comparable safety profiles to PCV13. Baseline IgG GMCs and OPA GMTs were comparable across vaccination groups. At 30 days postvaccination, both PCV15 formulations induced serotype specific antibodies to all 15 serotypes in the vaccine. IgG GMCs and OPA GMTs in recipients of either PCV15 formulation were non-inferior (≤ 2-fold margin) to those measured in recipients of PCV13 for shared serotypes and superior (> 1.0-fold difference) for serotypes unique to PCV15. Formulation B generally induced higher immune responses than Formulation A. CONCLUSION: In healthy adults ≥ 50 years of age, both new formulations of PCV15 displayed acceptable safety profiles and induced serotype-specific immune responses comparable to PCV13.

Safety and immunogenicity of VAQTA® in children 12-to-23 months of age with and without administration of other US pediatric vaccines.

Safety and immunogenicity data from 5 clinical trials conducted in the US in children 12-to-23 months old where HAVi was administered alone or concomitantly with other pediatric vaccines (M-M-R®II, Varivax®, TRIPEDIA®, Prevnar®, ProQuad®, PedvaxHIB®, and INFANRIX®) were combined. Among 4,374 participants receiving ≥ 1 dose of HAVi, 4,222 (97%) had safety follow-up and the proportions reporting adverse events (AE) were comparable when administered alone (69.4%) or concomitantly with other pediatric vaccines (71.1%). The most common solicited injection-site AEs were pain/tenderness (Postdose 1: 25.8%; Postdose 2: 26.1%) and redness (Postdose 1: 13.6%; Postdose 2: 15.1%). The most common vaccine-related systemic AEs were fever (≥ 100.4ºF, 12.2%) and irritability (8.1%). Serious AEs (SAEs) were observed at a rate of 0.4%; 0.1% were considered vaccine-related. No deaths were reported within 14 days following a dose of HAVi. These integrated analyses also showed that protective antibody concentrations were elicited in 100% of toddlers after two doses and 92% after a single dose, regardless of whether HAVi was given concomitantly with other vaccines or alone. These results demonstrate that HAVi was well-tolerated whether given alone or concomitantly with other vaccines, with a low incidence of vaccine-related SAEs. HAVi was immunogenic in this age group regardless of whether administered with or without other pediatric vaccines and whether 1 or 2 doses were administered. HAVi did not impact the immune response to other vaccines. These data continue to support the routine use of HAVi with other pediatric vaccines in children ≥ 12 months of age.

Impact of Out-of-Pocket Cost on Herpes Zoster Vaccine Uptake: An Observational Study in a Medicare Managed Care Population.

Herpes zoster (HZ) vaccination is approved for adults aged 50+ for the prevention of HZ, but it is underutilized. The objective of this study was to evaluate the association between out-of-pocket cost and HZ vaccine utilization. Adults aged 65 or older enrolled for at least 12 months in Medicare Advantage/Part D (MAPD) and Medicare Part D only (PDP) plans from 1 January 2007 to 30 June 2014 were selected. Abandonment was defined as a reversed claim for HZ vaccine with no other paid claim within 90 days. Out-of-pocket costs used were actual amounts recorded in the claim. Overall, the HZ vaccine abandonment rate was 7.3%. Mean out-of-pocket costs were higher for individuals who abandoned versus those who did not ($88 (±$55) versus $80 (± $49)). Logistic regression indicated individuals with out-of-pocket costs of $80⁻$90 were 21% more likely (OR = 1.21, 1.16⁻1.27 95% CI), and those with out-of-pocket costs >$90 were 90% more likely (OR = 1.90, 1.85⁻1.96 95% CI) to abandon than those with out-of-pocket costs <$80. The models also suggested that socioeconomic, racial, and ethnic disparities in vaccine abandonment existed. Different vaccine targeting efforts and pharmacy benefit design strategies may be needed to increase use, improve adherence, and minimize disparities.

A cross-sectional survey of work and income loss consideration among patients with herpes zoster when completing a quality of life questionnaire.

BACKGROUND: Prior research suggests that many patients do not spontaneously include work/income loss when responding to utility assessments, although this remains unconfirmed in the US due to almost no published US-based studies to date, and has not been previously studied among patients with herpes zoster (HZ). The objective of this study was to examine whether patients with HZ consider work and income loss when completing a quality of life survey. METHODS: A cross-sectional survey was administered to 2000 US adult commercial health plan enrollees aged 50-64 years with ≥ 1 HZ medical claim during 2014. The survey collected information related to health status (EQ-5D), work productivity, and HZ severity and clinical features. RESULTS: Mean respondent age was 58.4 years [standard deviation (SD) 4.1] and 62.0% were female. About 3 in 4 (76.8%) patients (N = 772) were employed either full (69.9%) or part time (6.9%). Less than half (45%) spontaneously considered work/income loss when responding to EQ-5D, and mean EQ-5D scores for patients who considered work/income loss were lower than for patients who did not [0.56 (SD = 0.28) vs. 0.69 (SD = 0.24); p < 0.001]. Overall, 43% of patients reported at least one full day missed (mean = 9 full days) and 29% reported at least one partial day missed (mean = 6 partial days) during the most recent shingles episode. Patients who considered work loss were more likely to have missed full (76.4% vs 26.0%, p < 0.001) or partial (70.9% vs. 35.2%, p < 0.001) days. Patients with absenteeism were more likely to consider work/income loss when completing EQ-5D [odds ratio (OR) = 7.91, 95% confidence interval (CI) 5.01-12.31]. Odds of absenteeism/presenteeism increased significantly with increasing levels of HZ severity, and higher odds were associated with pain located on the face/scalp/neck/eye/ear (OR 1.90, 95% CI 1.06-3.40) and with pain lasting 12+ months (OR = 2.91, 95% CI 1.14-7.42). CONCLUSIONS: HZ has considerable impact on the work and productivity of adults aged 50-64 years old. However, many patients with HZ do not spontaneously consider work/income loss when completing a standardized quality of life questionnaire. Studies that use health state utilities in HZ based on EQ-5D may not fully reflect the societal costs of work loss.

Measuring herpes zoster disease burden in São Paulo, Brazil: a clinico-epidemiological single-center study.

OBJECTIVES: Herpes zoster is characterized by acute neuritis and post-herpetic neuralgia. Currently, data concerning the zoster-associated impact on quality of life and healthcare resource utilization in Brazil are scarce. This study measured the zoster-associated burden in a Brazilian population. METHODS: This was a prospective, observational, single-cohort study conducted in a primary hospital's emergency room in São Paulo, Brazil. Patients enrolled at various timepoints during a zoster episode were followed over 180 days. The Zoster Brief Pain Inventory and the Initial Zoster Impact Questionnaire assessed zoster-associated pain. The EuroQoL assessed the impact of herpes zoster and/or zoster-associated pain on quality of life. Healthcare resource utilization was assessed by patient-reported questionnaires. RESULTS: One-hundred forty-six zoster patients were enrolled [mean (SD) age of 69.9 (10.9) years]. Mean (SD) worst pain scores decreased from 5.3 (3.5) at baseline to 1.9 (3.0) 180 days following rash onset. Mean (SD) EuroQoL scores significantly decreased from 0.9 (0.2) before rash appearance to 0.7 (0.2) after rash onset (p<0.001), followed by gradual improvements in quality of life over 180 days, with pre-herpes zoster quality of life achieved at the end of the observation period. The majority of patients purchased prescription medications (89.7%) and required doctor's office visits (65.8%) for zoster episodes. CONCLUSIONS: Herpes zoster is associated with a significant disease burden, including zoster-associated pain, impaired quality of life and increased healthcare resource utilization in Brazil. These results support the implementation of early intervention and prevention programs such as vaccinations to reduce the herpes zoster-associated disease burden in Brazil.

Public health impact and cost effectiveness of routine childhood vaccination for hepatitis a in Jordan: a dynamic model approach.

BACKGROUND: As the socioeconomic conditions in Jordan have improved over recent decades the disease and economic burden of Hepatitis A has increased. The purpose of this study is to assess the potential health and economic impact of a two-dose hepatitis A vaccine program covering one-year old children in Jordan. METHODS: We adapted an age-structured population model of hepatitis A transmission dynamics to project the epidemiologic and economic impact of vaccinating one-year old children for 50 years in Jordan. The epidemiologic model was calibrated using local data on hepatitis A in Jordan. These data included seroprevalence and incidence data from the Jordan Ministry of Health as well as hospitalization data from King Abdullah University Hospital in Irbid, Jordan. We assumed 90% of all children would be vaccinated with the two-dose regimen by two years of age. The economic evaluation adopted a societal perspective and measured benefits using the quality-adjusted life-year (QALY). RESULTS: The modeled vaccination program reduced the incidence of hepatitis A in Jordan by 99%, 50 years after its introduction. The model projected 4.26 million avoided hepatitis A infections, 1.42 million outpatient visits, 22,475 hospitalizations, 508 fulminant cases, 95 liver transplants, and 76 deaths over a 50 year time horizon. In addition, we found, over a 50 year time horizon, the vaccination program would gain 37,502 QALYs and save over $42.6 million in total costs. The vaccination program became cost-saving within 6 years of its introduction and was highly cost-effective during the first 5 years. CONCLUSION: A vaccination program covering one-year old children is projected to be a cost-saving intervention that will significantly reduce the public health and economic burden of hepatitis A in Jordan.

Herpes zoster incidence and cost in patients receiving autologous hematopoietic stem-cell transplant.

OBJECTIVE: Among patients receiving autologous hematopoietic stem cell transplant (Auto-HSCT), this study estimated the incidence of herpes zoster (HZ), compared healthcare costs among patients with and without HZ, and evaluated antiviral prophylaxis (AP) use. RESEARCH DESIGN AND METHODS: A retrospective study was conducted using data from a large health plan to identify patients ≥18 years with ≥1 claim for an Auto-HSCT procedure during 2006-2011 (n = 2,530). Patients were followed from date of Auto-HSCT until risk-end date, defined as development of HZ, end of enrollment, death, or December 31, 2011. HZ incidence was calculated as cases observed after Auto-HSCT, divided by accrued time-at-risk in person-years (PY). AP use and duration were defined by prescription fills. One-year medical and pharmacy costs were calculated as combined health plan and patient paid amounts. MAIN OUTCOME MEASURES: HZ incidence and healthcare costs were calculated using administrative claims data. RESULTS: Overall HZ incidence was 62.2/1,000 PY (95% CI = 54.3-70.9). Most (72.3%) patients were prescribed AP. During the first 90-days post-Auto-HSCT, patients without AP had increased incidence (151.6/1,000 PY, 95% CI = 88.3-242.6) compared to those prescribed AP pre- (30.9/1,000 PY, 95% CI = 11.3-67.2) or post-Auto-HSCT (33.0/1,000 PY, 95% CI = 13.3-67.9). Total adjusted mean 1-year all-cause healthcare costs were $74,875 for patients who developed HZ and $70,279 for patients who did not (difference = $4,596 (cost ratio = 1.07, 95% CI = 0.86-1.32, p = .566)). CONCLUSIONS: HZ incidence was high, despite AP use. Mean annual healthcare costs were higher for patients with HZ, but the difference was not statistically significant. An effective vaccine against HZ could be useful in decreasing both incidence of and cost for HZ in this population.