Systematic Literature Review on the Incidence of Herpes Zoster in Populations at Increased Risk of Disease in the EU/EEA, Switzerland, and the UK.

INTRODUCTION: Older adults and patients with underlying conditions such as immunocompromised (IC) populations (e.g., due to medical conditions or immunosuppressive medication) are at increased risk for herpes zoster (HZ). The first HZ recombinant vaccine for IC patients was approved in 2020. Limited evidence exists to inform decision-makers on HZ incidence in high-risk patients in Europe. This systematic literature review (SLR) assessed HZ incidence across 14 high-risk populations in the European Union/European Economic Area, Switzerland, and the United Kingdom. METHODS: An SLR (Embase, Medline, 2002-2022, observational studies) was performed to identify HZ incidence (i.e., primary outcomes: rate or cumulative; secondary: relative incidence) in type 1 and 2 diabetes mellitus (DM); chronic obstructive pulmonary disease and asthma; depression; rheumatic disorders (RD); multiple sclerosis (MS); inflammatory bowel diseases (IBD); psoriasis; lupus; human immunodeficiency virus (HIV); solid organ transplantation (SOT); solid organ malignancy (SOM); hematologic malignancy (HM); and stem cell transplantation (SCT). RESULTS: Of 776 unique records screened, 59 studies were included (24 reported incidence rate per 1000 person-years; two, cumulative incidence per 1000 persons; and 33, relative incidence). The highest incidence rates were reported for SOT (12.1-78.8) and SCT (37.2-56.1); HM (2.9-32.0); RD (0.41-21.5); lupus (11.0-16.5); IC mixed population (11.3-15.5); HIV/AIDS (11.8-13.0); chronic respiratory diseases (4.7-11.4); SOM (8.8-11.0); IBD (7.0-10.8); DM (4.3-9.4); depression (7.2-7.6); MS (5.7-6.3); and psoriasis (5.3-6.1). In many high-risk populations, HZ incidence was higher for older age groups, women, and some treatments. CONCLUSIONS: The HZ incidence rate in Europe increased with age and varied across high-risk populations, with high rates for solid organ and stem cell transplants, cancer, and rheumatoid arthritis. Most studies were retrospective with methodological differences affecting generalizability and comparability. Future studies should stratify data by IC population, age, sex, severity, medication, and study timeframe.

Incidence and Burden of Herpes Zoster in Sweden: A Regional Population-Based Register Study.

INTRODUCTION: Herpes zoster (HZ) is a painful disease that mainly affects individuals whose immune system has been weakened because of increasing age (> 50 years) or certain diseases or treatments. We estimated the complete burden of HZ. METHODS: This population-based register study analysed healthcare data from the VEGA and Digitalis databases of Västra Götaland Region (VGR), Sweden. The VEGA database includes all patients in VGR, covering both hospital and primary care. The Digitalis records prescribed medications. The study population included patients aged ≥ 18 years with at least one registered primary or secondary HZ diagnosis (based on International Classification of Diseases [ICD] codes) between 2005 and 2021. Incidence rates (95% confidence intervals [CI]) were stratified by age, sex and diagnosis/analgesic prescription. RESULTS: Overall HZ incidence increased from 2.5 (95% CI 2.4-2.6) in 2005 to 4.2 (95% CI 4.1-4.3) in 2021. The increase in incidence was rapid from 2005 to 2013, followed by a plateauing trend. From 2014-2019, the lifetime risk of HZ, excluding recurrent cases, was 36.5% (95% CI 35.5-37.4%). Municipal differences ranged from 34.4% (95% CI 32.5-36.4%) to 43.6% (95% CI 39.9-47.4%). Recurrence rates of HZ were 8.7% and 9.1% with follow-up periods of 5.5 and 10.5 years, respectively. Reported postherpetic neuralgia (PHN) cases increased five-fold over the study period. In 2019, 19% of all HZ patients developed HZ-related neuropathic pain; 13.6% had signs of persistent pain (> 90 days; i.e. PHN). An increased occurrence of cerebral and cardiovascular disease was observed in HZ patients. Among high-risk groups the occurrence of HZ peaked among those with inflammatory and autoimmune diseases. CONCLUSION: HZ and PHN risk in Sweden is comparable to that in other European countries prior to implementing HZ national vaccination programs. Municipal differences suggest that the lifetime risk of HZ in Sweden is at least 36.5%. CLINICAL TRIAL REGISTRATION: NCT Number ( www. CLINICALTRIALS: gov ).

What is the context?The varicella-zoster virus (VZV) can reactivate after primary infection and cause herpes zoster or shingles.Shingles is painful and mostly affects people aged > 50 years or those who have weakened immunity due to age, illness or medical treatments.The National Immunization Program (NIP) in Sweden does not currently include vaccination against shingles.We evaluated how often individuals from Västra Götaland Region, Sweden, experienced shingles and its complications.What is new?Overall, the number of shingles and PHN cases increased significantly from 2005 to 2021.We found that 14% of patients with shingles had pain persisting for > 3 months after a shingles episode.Most people developing shingles (about 70%) are healthy individuals without comorbidities, although those with underlying health issues have more risk of getting shingles.Over a follow-up period of 5.5 years, 8.7% of patients with shingles had more than one shingles episode.What is the impact?The occurrence of shingles and postherpetic neuralgia in Sweden is higher than what was reported previously and is comparable to other European countries before the implementation of shingles vaccination programmes.

Knowledge, Attitudes, and Practices of European Healthcare Professionals towards Hepatitis A and Hepatitis B Vaccination in at-Risk Adults.

Despite the occurrence of several hepatitis A (hepA) and hepatitis B (hepB) outbreaks in Europe in the last few decades, not all European countries have implemented hepA and hepB vaccinations in their national immunization programs, especially for adults at risk for hepA and/or hepB infection, such as men who have sex with men or patients with chronic liver disease. Currently, little is known on the attitudes of European healthcare professionals (HCPs) towards hepA and hepB vaccinations for at-risk adults. We conducted an online survey among HCPs in Germany, Spain, and the United Kingdom to assess their awareness of and adherence to their national hepA and hepB vaccination guidelines for at-risk adults. Among the 698 HCPs who took the survey, most (91.1%) were familiar with their national vaccination recommendations and always followed them or followed them most of the time when advising or prescribing hepA or hepB vaccines. Major and moderate barriers for recommending or administering such vaccines were the non-disclosure of risk factors by the patient (53.0-57.6%) and the patient's lack of motivation or knowledge about the risk of the disease (50.3-52.9%). These results may help inform strategies to improve and accelerate hepA and hepB vaccination in European at-risk adults.

Unmet needs in uncomplicated urinary tract infection in the United States and Germany: a physician survey.

BACKGROUND: Uncomplicated urinary tract infections (uUTIs/acute cystitis) are among the most common infections in women worldwide. There are differences in uUTI treatment guidelines between countries and understanding the needs of physicians in diverse healthcare systems is important for developing new treatments. We performed a survey of physicians in the United States (US) and Germany to understand their perceptions of, and management approaches to uUTI. METHODS: This was a cross-sectional online survey of physicians in the US and Germany who were actively treating patients with uUTI (≥ 10 patients/month). Physicians were recruited via a specialist panel and the survey was piloted with 2 physicians (1 US, 1 Germany) prior to study commencement. Data were analyzed with descriptive statistics. RESULTS: A total of 300 physicians were surveyed (n = 200 US, n = 100 Germany). Across countries and specialties, physicians estimated 16-43% of patients did not receive complete relief from initial therapy and 33-37% had recurrent infections. Urine culture and susceptibility testing was more common in the US and among urologists. The most commonly selected first-line therapy was trimethoprim-sulfamethoxazole in the US (76%) and fosfomycin in Germany (61%). Ciprofloxacin was the most selected following multiple treatment failures (51% US, 45% Germany). Overall, 35% of US and 45% of German physicians agreed with the statement "I feel there is a good selection of treatment options" and ≥ 50% felt that current treatments provided good symptom relief. More than 90% of physicians included symptom relief amongst their top 3 treatment goals. The overall impact of symptoms on patients' lives was rated "a great deal" by 51% of US and 38% of German physicians, increasing with each treatment failure. Most physicians (> 80%) agreed that antimicrobial resistance (AMR) is serious, but fewer (56% US, 46% Germany) had a high level of confidence in their knowledge of AMR. CONCLUSIONS: Treatment goals for uUTI were similar in the US and Germany, although with nuances to disease management approaches. Physicians recognized that treatment failures have a significant impact on patients' lives and that AMR is a serious problem, though many did not have confidence in their own knowledge of AMR.

Activity impairment, health-related quality of life, productivity, and self-reported resource use and associated costs of uncomplicated urinary tract infection among women in the United States.

BACKGROUND: Uncomplicated urinary tract infections (uUTIs) are among the most common infections in the US. Only a few studies, however, describe the impact of uUTIs from the patient perspective. METHODS: A cross-sectional online survey of US women aged ≥18 years was performed assessing uUTI burden regarding activity impairment, health-related quality of life (HRQoL), workplace productivity, healthcare resource use (HRU), and costs. Participants who self-reported a uUTI in the prior 60 days treated with ≥1 oral antibiotic were included. Activity impairment was assessed with the Activity Impairment Assessment scale. HRQoL was assessed using a modified Short Form 36 (SF-36). Direct costs were sum of out-of-pocket expenditures and monetized HRU; indirect costs were calculated using Work Productivity and Activity Impairment (WPAI). Participants were stratified by uUTI recurrence, number of prescribed antibiotics for recent uUTI and therapy appropriateness (1 first-line/1 second-line/multiple antibiotics). Multivariable regression analysis assessed the relationship between stratifications and outcomes while controlling for demographic/clinical characteristics. Propensity score matching was used to compare participants to a matched population from the 2020 National Health and Wellness Survey (NHWS), to control for any impact of COVID-19 on responses. RESULTS: Among 375 participants, impaired activities included sexual intercourse (66.9%), sleep (60.8%) and exercise (52.3%). HRQoL was worse (p<0.0001) than the NHWS population (46.4 vs. 51.3 [physical component score]; 40.0 vs. 46.9 [mental component score]; 0.63 vs. 0.72 [health utility index]). All included WPAI assessments were worse for uUTI cohort vs. NHWS (p<0.0001). Adjusted direct costs were higher for participants receiving 2 vs. 1 antibiotic ($2090 vs. $776; p<0.0001) and receiving multiple antibiotics vs. 1 first-line ($1642 vs. $875; p = 0.002). Recurrent uUTI was associated with increased activity impairment, worse HRQoL, and costs vs. non-recurrent. CONCLUSIONS: uUTIs were associated with increased activity impairment, worse productivity, and reduced HRQoL. Higher costs were found vs. a matched population.

Estimated public health impact of human rotavirus vaccine (HRV) and pneumococcal polysaccharide protein D-conjugate vaccine (PHiD-CV) on child morbidity and mortality in Gavi-supported countries.

Vaccine impact models against rotavirus disease (RD) and pneumococcal disease (PD) in low- and middle-income countries assume vaccine coverage based on other vaccines. We propose to assess the impact on severe disease cases and deaths avoided based on vaccine doses delivered by one manufacturer to Gavi-supported countries. From the number of human rotavirus vaccine (HRV) and pneumococcal polysaccharide protein D-conjugate vaccine (PHiD-CV) doses delivered, we estimated the averted burden of disease 1) in a specific year and 2) for all children vaccinated during the study period followed-up until 5 years (y) of age. Uncertainty of the estimated impact was assessed in a probabilistic sensitivity analysis using Monte-Carlo simulations to provide 95% confidence intervals. From 2009 to 2019, approximately 143 million children received HRV in 57 Gavi-supported countries, avoiding an estimated 18.7 million severe RD cases and 153,000, deaths. From 2011 to 2019, approximately 146 million children received PHiD-CV in 36 countries, avoiding an estimated 5.0 million severe PD cases and 587,000 deaths. The number of severe cases and deaths averted for all children vaccinated during the study period until 5 years of age were about 23.2 million and 190,000, respectively, for HRV, and 6.6 million and 749,000, respectively, for PHiD-CV. Models based on doses delivered help to assess the impact of vaccination, plan vaccination programs and understand public health benefits. In 2019, HRV and PHiD-CV doses delivered over a 5-y period may have, on average, averted nine severe disease cases every minute and one child death every 4 min.

What is the context?The WHO added the pneumococcal conjugate vaccine and the rotavirus vaccine in the recommended vaccination schedule of all countries in 2007 and 2009, respectively.Previous studies estimated the public health benefit of these vaccines by approximating the number of children who received them.What is new?We used an alternative approach to estimate the benefit based on actual number of doses of the vaccines, human rotavirus vaccine (HRV; Rotarix) and pneumococcal polysaccharide protein D-conjugate vaccine (PHiD-CV; Synflorix) delivered to each country considered.The study analyzed data from children under 5 years of age in 60 Gavi-supported countries by identifying the number of vaccine doses delivered, estimating the number of children fully covered, applying the country-specific disease epidemiology, estimating the number of severe disease cases and deaths avoided.From 2009 to 2019, approximately 143 million children were vaccinated with HRV avoiding an estimated 18.7 million severe rotavirus disease cases and 153,000 deaths.From 2011 to 2019, about 146 million children were vaccinated with pneumococcal vaccine avoiding an estimated 5.0 million severe pneumococcal disease cases and 587,000 deaths.What is the impact? The benefit of HRV and PHiD-CV in Gavi-supported countries is often estimated based on assumptions of vaccine coverage rates.A modeling approach based on doses delivered by the vaccine manufacturer can provide an additional view on the potential vaccine benefits and improve planning, contribution, and sustainability of the immunization programs at a country level.In 2019, HRV and PHiD-CV together averted nine cases of severe disease each minute and one child death every 4 minutes.

Treatment patterns, healthcare resource use, and costs associated with uncomplicated urinary tract infection among female patients in the United States.

BACKGROUND: We evaluated associations between antibiotic prescription and healthcare resource use and costs (Part A), and between antibiotic switching and healthcare resource use, costs, and uncomplicated urinary tract infection recurrence (Part B) in female patients with uncomplicated urinary tract infection in the United States. METHODS: This retrospective cohort study of linked Optum and Premier Healthcare Database data included female patients ≥12 years old with an uncomplicated urinary tract infection diagnosis (index date), who were prescribed antibiotics during an outpatient/emergency department visit between January 1, 2013 and December 31, 2018. In Part A, patients were stratified by antibiotic prescription appropriateness: appropriate and optimal (compliant with Infectious Diseases Society of America 2011 guidelines for drug class/treatment duration) versus inappropriate/suboptimal (inappropriate drug class/treatment duration per Infectious Diseases Society of America 2011 guidelines, and/or treatment failure). In Part B, patients were stratified by treatment pattern (antibiotic switch vs no antibiotic switch). Healthcare resource use and costs during index episode (within 28 days of index date) and 12-month follow-up were compared. RESULTS: Of 5870 patients (mean age 44.5 years), 2762 (47.1%) had inappropriate/suboptimal prescriptions and 567 (9.7%) switched antibiotic. Inappropriate/suboptimal prescriptions were associated with higher healthcare resource use (mean number of ambulatory care and pharmacy claims [both p < 0.001]), and higher total mean cost (inpatient, outpatient/emergency department, ambulatory visits, and pharmacy costs) per patient ($2616) than appropriate and optimal prescriptions ($649; p < 0.001) (Part A). Antibiotic switching was associated with more pharmacy claims and higher total mean costs (p ≤ 0.01), and a higher incidence of recurrent uncomplicated urinary tract infection (18.9%) than no antibiotic switching (14.2%; p < 0.001) (Part B). CONCLUSIONS: Inappropriate/suboptimal prescriptions and antibiotic switching were associated with high costs, ambulatory care, and pharmacy claims, suggesting a need for improved uncomplicated urinary tract infection prescribing practices in the United States.

Impact of suboptimal or inappropriate treatment on healthcare resource use and cost among patients with uncomplicated urinary tract infection: an analysis of integrated delivery network electronic health records.

BACKGROUND: Although uncomplicated urinary tract infections (uUTIs; occurring in female patients without urological abnormalities or history of urological procedures or complicating comorbidities) are one of the most common community infections in the United States (US), limited data are available concerning associations between antibiotic resistance, suboptimal prescribing, and the economic burden of uUTI. We examined the prevalence of suboptimal antibiotic prescribing and antibiotic resistance and its effects on healthcare resource use and costs. METHODS: This retrospective cohort study utilized electronic health record data from a large Mid-Atlantic US integrated delivery network database, collected July 2016-March 2020. Female patients aged ≥ 12 years with a uUTI, who received ≥ 1 oral antibiotic treatment within ± 5 days of index uUTI diagnosis, and had ≥ 1 urine culture with antimicrobial susceptibility test, were eligible for inclusion in the study. The study examined the proportion of antibiotics that were inappropriately or suboptimally prescribed among patients with confirmed uUTI, and total healthcare costs (all-cause and UTI-related) within 6 months after a uUTI, stratified by antibiotic susceptibility and/or inappropriate or suboptimal treatment. Patient outcomes were assessed after 1:1 propensity score matching of patients with antibiotic-susceptible versus not-susceptible isolates and then by other covariates (e.g., demographics and recent healthcare use). A similar propensity score calculation was used to analyze the effect of inappropriate/suboptimal treatment on health outcomes. Costs were adjusted to 2020 US dollars ($). RESULTS: Among 2565 patients with a uUTI included in the analysis, the most commonly prescribed antibiotics were nitrofurantoin (61%), trimethoprim-sulfamethoxazole (19%), and ciprofloxacin (15%). More than one-third of the sample (40.2%) had isolates that were not-susceptible to ≥ 1 antibiotic indicated for treating patients with uUTI. Two-thirds (66.6%) of study-eligible patients were prescribed appropriate treatment; 29.9% and 11.9% were prescribed suboptimal and/or inappropriate treatment, respectively. Inappropriate or suboptimally prescribed patients had greater all-cause and UTI-related costs compared with appropriately prescribed patients. Differences were most striking among patients with antibiotic not-susceptible isolates. CONCLUSIONS: These findings highlight how the increasing prevalence of antibiotic resistance combined with suboptimal treatment of patients with uUTI increases the burden on healthcare systems. The finding underlines the need for improved prescribing accuracy by better understanding regional resistance rates and developing improved diagnostic tests.

Economic burden of antibiotic-not-susceptible isolates in uncomplicated urinary tract infection: Analysis of a US integrated delivery network database.

BACKGROUND: Uncomplicated urinary tract infections (uUTIs) are one of the most common bacterial infections in the United States (US). Contemporary data are important for understanding the health economic impact of antimicrobial-resistant uUTIs. We compared the economic burden among patients with uUTI isolates susceptible or not-susceptible to the initial antibiotic prescription. METHODS: This retrospective cohort study utilized electronic health record data (1 July 2016-31 March 2020) from a large Mid-Atlantic US integrated delivery network database. Patients were females aged ≥ 12 years with a uUTI, who received oral antibiotic treatment and had ≥ 1 urine culture within ± 5 days of diagnosis. The primary outcome was the difference in healthcare resource use and costs (all-cause, urinary tract infection [UTI]-related) among patients with susceptible versus not-susceptible isolates during the 6 months after the index uUTI diagnosis. Secondary outcomes included: pharmacy costs, hospital admissions and emergency department visits, as well as the probability of uUTI progressing to complicated UTI (cUTI) between patients with susceptible and not-susceptible isolates. Patient outcomes were compared using 1:1 propensity score matching. Winsorized costs were adjusted to 2020 quarter 1 US dollars ($). RESULTS: A total of 2565 patients were eligible for analysis. The propensity score-matched sample comprised 2018 patients, with an average age of 44.0 and 41.0 years for the susceptible and not-susceptible populations, respectively. In the 6 months post-index uUTI event, patients with not-susceptible isolates had significantly more all-cause prescriptions orders (+ 1.41 [P = 0.001]), UTI-related prescriptions orders (+ 0.26 [P < 0.001]) and a higher probability of all-cause inpatient (+ 1.4% [P = 0.009]), outpatient (+ 6.1% [P = 0.006]), or UTI-related outpatient (+ 3.7% [P = 0.039]) encounters. Patients with a uUTI and an antibiotic-not-susceptible isolate were significantly more likely to progress to cUTI than those with susceptible isolates (odds ratio: 2.35 [confidence interval: 1.66-3.33; P < 0.001]). Over 6 months, patients with not-susceptible versus susceptible isolates had significantly higher all-cause costs (+ $426 [P = 0.031]) and UTI-related costs (+ $157 [P = 0.034]). CONCLUSIONS: Patients with a uUTI caused by antibiotic-not-susceptible isolates had higher healthcare resource usage, costs, and increased likelihood of progressing to cUTI than those with antibiotic-susceptible isolates.

Cost effectiveness and budget impact of universal varicella vaccination in Russia.

This economic evaluation assesses the cost-effectiveness and budget impact of introducing a two-dose varicella vaccine in the Russian national immunization program. A static Markov model followed a simulated 2019 Russian cohort over its lifetime and compared outcomes and costs of three varicella vaccination strategies: strategy I (doses given at 12 and 15 months of age), strategy II (doses given at 1 year and 6 years of age), and a no vaccination scenario. Inputs on age-dependent clinical pathways, associated costs, and related health outcomes were collected from national sources and published literature. Results are presented as incremental cost-effectiveness ratio (ICER) from the healthcare payer and societal perspective over the lifetime of the birth cohort and the budget impact over a 10 years' time horizon. Vaccination strategies I and II resulted in an ICER of approximately 1.7 million rubles per quality-adjusted life years gained from the healthcare payer perspective and were cost-saving from the societal perspective. From the healthcare payer perspective, the costs per varicella case averted were 5,989 and 7,140 rubles per case for strategies I and II, respectively. However, from the societal perspective, vaccination is a dominant strategy and the budget impact analysis shows significant healthcare savings over 10 years, with strategy I realizing savings of ~2 billion rubles more than strategy II. From a public health impact perspective, varicella vaccination of children at 12 and 15 months of age through the Russian NIP is expected to be cost-effective with an affordable budget impact compared to no vaccination.

A graphical version of the plain language summary can be found here: 10.6084/m9.figshare.19291463Focus on the patientWhat is the context? Varicella, or chickenpox, is a highly contagious infection. Though mild in children, complications can occur in older individuals, increasing the economic burden for society and public health institutions.In 2019, approximately 0.6% of the Russian population was impacted by varicella, a vaccine-preventable disease.In Russia, varicella vaccination is only implemented in some regions. These regions report a decreasing trend in infection rates in the groups covered by vaccination.What is new? This study assesses the public health and economic impact of implementing varicella vaccination in Russia through its National Immunization Program.We compared two vaccination strategies to a no vaccination scenario: º Strategy I: two doses at 12 and 15 months of ageº Strategy II: two doses at 1 and 6 years of age Over a 10-year period, we found that: º Strategy I prevented 607,682 cases, 2,388,659 general practitioner visits and 10,256 hospitalizations, and saved 6.2 million rublesº Strategy II prevented 491,084 cases, 1,805,668 general practitioner visits and 10,108 hospitalizations, and saved 4.2 million rubles Strategy I saves more direct (i.e., general practitioner visits, hospitalizations and treatment) and indirect (i.e., income loss, disability payments, and caregiving) costs to society than strategy II.What is the impact? Varicella vaccination, especially when introduced at 12 and 15 months (strategy I) in the National Immunization Program, provides public health and economic benefits.From the healthcare payer perspective: this is a cost-effective intervention. From the societal perspective: the budget impact analysis shows significant savings.

A systematic literature review to assess the burden of herpes zoster disease in China.

INTRODUCTION: Herpes zoster (HZ) or shingles occurs as a result of reactivation after a primary infection with varicella zoster virus (chickenpox). The burden of HZ in older adults in China is not well understood. We conducted a systematic literature review to understand the burden of disease related to HZ, its complications, and associated costs in China. AREAS COVERED: Using publications retrieved from Chinese and English literature databases, we described incidence and prevalence of HZ, occurrence of HZ-related complications, and costs associated with HZ in mainland China, Taiwan, and Hong Kong. EXPERT OPINION: The data, although limited, indicate that the burden of disease due to HZ is substantial in China, with incidence rates that are comparable to the rest of the world. Recently, an adjuvanted recombinant HZ vaccine was approved for use in China. Disease prevention is likely to reduce the burden of disease, with potentially significant economic benefits. However, understanding the public health impact of vaccination in China will require extensive baseline information about incidence, complication rates, and associated costs. This review gives an overview of available research, but also reveals existing gaps. Well-designed observational studies are needed to quantify the total burden of disease and potential impact of prevention through vaccination.

PLAIN LANGUAGE SUMMARY What is the context? Although Herpes zoster (shingles) is a common disease of older age, the burden of disease in China is not well described. 32% of the Chinese population is aged 50 years and Older and this proportion is increasing. As a result of the ageing population, the public burden associated with shingles is expected to increase over time. What is new? We accessed published studies in the English and Chinese language literature to explore available information describing shingles in China. The incidence of shingles in Taiwan, Hong Kong and mainland China appears to be similar to other countries, although reliable population-based data are currently sparse in Hong Kong and mainland China. What is the impact? Data describing the disease burden due to shingles are currently heterogeneous throughout China. This review is a first step to determine those populations which could benefit most from shingles vaccination. Preventing shingles through vaccination could benefit the individual as well as provide potentially significant economic benefits for the individual, the employer and the economy.

How to assess for the full economic value of vaccines? From past to present, drawing lessons for the future.

Background:Cost-effectiveness analysis (CEA) is the economic analysis method most commonly applied today in the context of replacing one treatment with a new one in a developed healthcare system to improve efficiency. CEA is often requested by local healthcare decision-makers to grant reimbursement. New preventative interventions, such as new vaccines, may however have much wider benefits inside and outside healthcare, when compared with treatment. These additional benefits include externalities on indirect clinical impact, reallocation of specific healthcare resources, improved quality of care, better productivity, better disease control, better fiscal revenues, and others. But these effects are sometimes difficult to integrate into a meaningful CEA result. They may appear as specific benefits for specific stakeholders, other than the stakeholders in healthcare. Objective: Based on a historical view about the application of economic assessments for vaccines our objective has been to make the inventory of who was/is interested in knowing the economic value of vaccines, in what those different stakeholders are likely to see the benefit from their perspective and how  were/are we able to measure those benefits and to report them well. Results: The historical view disclosed a limited interest in the economic assessment of vaccines at start, more than 50 years ago, that was comparable to the assessment of looking for more efficiency in new industries through optimization exercises. Today, we are exposed to a very rich panoply of different stakeholders (n= 16). They have their specific interest in many different facets of the vaccine benefit of which some are well known in the conventional economic analysis (n=9), but most outcomes are hidden and not enough evaluated and reported (n=26). Meanwhile we discovered that many different methods of evaluation have been explored to facilitate the measurement and reporting of the benefits (n=18). Conclusion: Our recommendation for future economic evaluations of new vaccines is therefore to find the right combination among the three entities of stakeholder type selection, outcome measure of interest for each stakeholder, and the right method to apply. We present at the end examples that illustrate how successful this approach can be.

Ten years of experience with the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (Synflorix) in children.

Introduction: Pneumococcal diseases (including pneumonia, meningitis and sepsis) are among the leading vaccine-preventable causes of death in under-5-year-olds. Pneumococci are also one of the main bacterial pathogens associated with acute otitis media (AOM). Infant immunization programs with pneumococcal conjugate vaccines (PCVs) have led to stark reductions in pneumococcal disease rates.Areas covered: We summarized the development of the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) and evidence of its protective effect in children, since its licensure one decade ago. We highlighted the most recent data from post-licensure studies on invasive pneumococcal disease (IPD), pneumonia and AOM and from health economic evaluations. We present results from a model estimating PHiD-CV's impact on pneumococcal-related deaths.Expert opinion: Recent data from post-licensure studies confirm the previously demonstrated positive impact of PHiD-CV on IPD, pneumonia, AOM and AOM-related interventions (e.g., antibiotic use). Despite the success of infant PHiD-CV (and other PCV) programs, pneumococcal diseases still pose a substantial public health burden. Further reducing this burden will require improving access to currently available PCVs, increasing vaccination coverage and addressing the remaining burden due to non-vaccine serotypes. Future availability of lower-cost PCVs, PCVs with a broader serotype coverage and serotype-independent vaccines may contribute to this.

Cost-Effectiveness Comparison of Pneumococcal Conjugate Vaccines in Turkish Children.

BACKGROUND: The 13-valent pneumococcal conjugate vaccine (PCV13) is used for universal infant vaccination in Turkey. OBJECTIVES: To assess the cost effectiveness of replacing PCV13 with pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). METHODS: A Markov cohort model with monthly cycles following 1 cohort of infants over a 10-year time horizon was used. Local input parameters were obtained from published sources and expert consultation whenever possible. The model was adapted to estimate the health benefits and economic impact of each vaccine on invasive pneumococcal disease, pneumonia, and acute otitis media (AOM). An annual discount rate of 3% was used for benefits and costs (2016 euros). RESULTS: Under base-case assumptions, vaccinating 1 birth cohort of 1 325 783 infants with PHiD-CV instead of PCV13 was predicted to have the same impact on meningitis and pneumonia, a similar impact on bacteremia (+30 cases), but greater reductions in AOM-related general practitioner visits (-34 955) and hospitalizations (-624). Assuming equal vaccine prices, PHiD-CV was predicted to be dominant over PCV13 (176 additional quality-adjusted life-years while saving €635 330 [discounted]). One-way sensitivity analysis indicated that varying the vaccine price differential had the largest effect on the incremental cost-effectiveness ratio, and then AOM parameters. Probabilistic sensitivity analysis predicted PHiD-CV to be dominant over PCV13 in 92.4% of simulations. CONCLUSIONS: Any difference in price between PHiD-CV and PCV13 is expected to be the key driver of vaccine choice for preventing childhood pneumococcal disease in Turkey. At price parity, PHiD-CV use is likely to be a dominant strategy over the use of PCV13.

Cost-utility of quadrivalent versus trivalent influenza vaccine in Brazil - comparison of outcomes from different static model types.

BACKGROUND: Influenza burden in Brazil is considerable with 4.2-6.4 million cases in 2008 and influenza-like-illness responsible for 16.9% of hospitalizations. Cost-effectiveness of influenza vaccination may be assessed by different types of models, with limitations due to data availability, assumptions, and modelling approach. OBJECTIVE: To understand the impact of model complexity, the cost-utility of quadrivalent versus trivalent influenza vaccines in Brazil was estimated using three distinct models: a 1-year decision tree population model with three age groups (FLOU); a more detailed 1-year population model with five age groups (FLORA); and a more complex lifetime multi-cohort Markov model with nine age groups (FLORENCE). METHODS: Analysis 1 (impact of model structure) compared each model using the same data inputs (i.e., best available data for FLOU). Analysis 2 (impact of increasing granularity) compared each model populated with the best available data for that model. RESULTS: Using the best data for each model, the discounted cost-utility ratio of quadrivalent versus trivalent influenza vaccine was R$20,428 with FLOU, R$22,768 with FLORA (versus R$20,428 in Analysis 1), and, R$19,257 with FLORENCE (versus R$22,490 in Analysis 1) using a lifetime horizon. Conceptual differences between FLORA and FLORENCE meant the same assumption regarding increased all-cause mortality in at-risk individuals had an opposite effect on the incremental cost-effectiveness ratio in Analysis 2 versus 1, and a proportionally higher number of vaccinated elderly in FLORENCE reduced this ratio in Analysis 2. DISCUSSION: FLOU provided adequate cost-effectiveness estimates with data in broad age groups. FLORA increased insights (e.g., in healthy versus at-risk, paediatric, respiratory/non-respiratory complications). FLORENCE provided greater insights and precision (e.g., in elderly, costs and complications, lifetime cost-effectiveness). CONCLUSION: All three models predicted a cost per quality-adjusted life year gained for quadrivalent versus trivalent influenza vaccine in the range of R$19,257 (FLORENCE) to R$22,768 (FLORA) with the best available data in Brazil (Appendix A).

Cost-utility of quadrivalent versus trivalent influenza vaccine in Brazil - comparison of outcomes from different static model types

ABSTRACT Background: Influenza burden in Brazil is considerable with 4.2-6.4 million cases in 2008 and influenza-like-illness responsible for 16.9% of hospitalizations. Cost-effectiveness of influenza vaccination may be assessed by different types of models, with limitations due to data availability, assumptions, and modelling approach. Objective: To understand the impact of model complexity, the cost-utility of quadrivalent versus trivalent influenza vaccines in Brazil was estimated using three distinct models: a 1-year decision tree population model with three age groups (FLOU); a more detailed 1-year population model with five age groups (FLORA); and a more complex lifetime multi-cohort Markov model with nine age groups (FLORENCE). Methods: Analysis 1 (impact of model structure) compared each model using the same data inputs (i.e., best available data for FLOU). Analysis 2 (impact of increasing granularity) compared each model populated with the best available data for that model. Results: Using the best data for each model, the discounted cost-utility ratio of quadrivalent versus trivalent influenza vaccine was R$20,428 with FLOU, R$22,768 with FLORA (versus R$20,428 in Analysis 1), and, R$19,257 with FLORENCE (versus R$22,490 in Analysis 1) using a lifetime horizon. Conceptual differences between FLORA and FLORENCE meant the same assumption regarding increased all-cause mortality in at-risk individuals had an opposite effect on the incremental cost-effectiveness ratio in Analysis 2 versus 1, and a proportionally higher number of vaccinated elderly in FLORENCE reduced this ratio in Analysis 2. Discussion: FLOU provided adequate cost-effectiveness estimates with data in broad age groups. FLORA increased insights (e.g., in healthy versus at-risk, paediatric, respiratory/non-respiratory complications). FLORENCE provided greater insights and precision (e.g., in elderly, costs and complications, lifetime cost-effectiveness). Conclusion: All three models predicted a cost per quality-adjusted life year gained for quadrivalent versus trivalent influenza vaccine in the range of R$19,257 (FLORENCE) to R$22,768 (FLORA) with the best available data in Brazil (Appendix A).