Global Prevalence of Varicella-Associated Complications: A Systematic Review and Meta-Analysis.

INTRODUCTION: Varicella (chickenpox) is an infectious disease caused by the varicella zoster virus affecting children, adolescents, and adults. Varicella symptoms are usually self-limiting; however, different complications with widespread and systemic manifestations can occur. This systematic literature review aims to explore and quantify varicella-associated complication rates. METHODS: Two databases (Embase and MEDLINE), congress abstracts, and reference lists of systematic reviews were screened to identify evidence on varicella complications. Complications were identified and grouped into 14 clinically relevant categories. Proportional meta-analyses were conducted using a random-effects model and tests for heterogeneity and publication bias were performed. Subgroup, sensitivity, and meta-regression analyses were also conducted. A total of 78 studies, spanning 30 countries, were included in the meta-analysis. RESULTS: Pooled prevalence was highest in severe varicella (22.42%; 95% confidence interval [CI] 10.13-37.77), skin-related complications (20.12%; 95% CI 15.48-25.20), and infection-related complications (10.03%; 95% CI 7.47-12.90). Cardiovascular (0.55%; 95% CI 0.08-1.33), genitourinary (1.17%; 95% CI 0.55-1.99), and musculoskeletal (1.54%; 95% CI 1.06-2.11) complications had the lowest pooled prevalence. The remaining complication categories ranged between 1% and 10%. Subgroup analysis showed that complications were more prevalent in children versus adults and in hospitalized patients versus outpatients. Meta-regression analysis found that no ecological level covariates were accurate predictors for the overall prevalence of varicella-associated complications. There was substantial heterogeneity and publication bias across all meta-analyses. CONCLUSION: Results suggest that different types of varicella-associated complications could be frequent, impacting quality of life, and healthcare resource utilisation and budgets. These findings are crucial to raise awareness of the health and economic burden of varicella disease.

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Assessing the Underestimation of Adult Pertussis Disease in Five Latin American Countries.

INTRODUCTION: Pertussis, a contagious respiratory disease, is underreported in adults. The study objective was to quantify underestimation of pertussis cases in adults aged ≥ 50 years in five Latin American countries (Argentina, Brazil, Chile, Mexico, Peru). METHODS: A previously published probabilistic model was adapted to adjust the number of pertussis cases reported to national surveillance systems by successive multiplication steps (proportion of pertussis cases seeking healthcare; proportion with a specimen collected; proportion sent for confirmatory testing; proportion positive for pertussis; proportion reported to passive surveillance). The proportions at each step were added in a random effects model to produce a pooled overall proportion, and a final multiplier was calculated as the simple inverse of this proportion. This multiplier was applied to the number of cases reported to surveillance to estimate the number of pertussis cases. Monte Carlo simulation with 10,000 iterations estimated median as well as upper and lower 90% values. Input data were obtained from surveillance systems and published sources. RESULTS: The estimated median underestimation factor for pertussis cases in adults ranged from 104 (90% limits 40, 451) in Chile to 114 (90% limits 39, 419) in Argentina. In all five countries, the largest estimated number of cases was in the group aged 50-59 years. The highest number per 100,000 population was in the group aged ≥ 90 years in most countries. The estimated median underestimation factor for pertussis hospitalizations was 2.3 (90% limits 1.8, 3.3) in Brazil and 2.4 (90% limits 1.8, 3.2) in Chile (data not available for other countries). CONCLUSION: This analysis indicates that the number of pertussis cases in adults aged ≥ 50 years in five Latin American countries is approximately 100 times higher than the number captured in surveillance data. These results could support decision-making in the diagnosis, management, and prevention of pertussis disease in adults.

Healthcare resource use and costs of varicella and its complications: A systematic literature review.

Varicella is a highly contagious disease caused by the varicella zoster virus (VZV). While the disease is usually mild, severe complications can occur requiring costly hospitalization. A thorough understanding of the healthcare resource use (HCRU) and costs of varicella is needed to inform health-economic models of preventive strategies. A systematic literature review was carried out to retrieve relevant publications between 1999 and 2021, reporting HCRU and cost outcomes for varicella and its complications. Data were extracted and stratified according to pre-specified age groups and complication categories. Costs were re-based to a $US2020 footing using both purchasing power parity and the medical component of consumer price indexes. Data were summarized descriptively due to high heterogeneity in study design and outcome reporting. Forty-four publications fulfilled the inclusion and exclusion criteria of which 28 were conducted in Europe, 6 in Middle East and Asia, 5 in South America, 3 in North America, and 2 in multiple regions. Primary healthcare visits accounted for 30% to 85% of total direct costs. Hospitalization costs varied between $1,308 and $38,268 per episode depending on country, complication type, and length of stay, contributing between 2% and 60% to total direct costs. Indirect costs, mostly driven by workdays lost, accounted for approximately two-thirds of total costs due to varicella. The management of varicella and related complications can lead to substantial HCRU and costs for patients and the healthcare system. Additional research is needed to further characterize the varicella-associated economic burden and its broader impact from a societal standpoint.

Varicella, also known as chickenpox, is a highly contagious infectious disease which affects mostly children. Indeed, >90% of children will have had chickenpox by the age of 12 years. The symptoms are usually mild, but in some cases, serious complications can occur such as pneumonia, bacterial superinfection of the skin and encephalitis. A clear understanding of the complications of chickenpox for patients and the healthcare system would be helpful so that countries can assess the true health and economic burden of the disease.In this study, we have summarized existing published data from around the world. We have included studies that reported on the number of varicella cases, doctor visits, hospitalizations, and costs due to varicella and associated complications.These data showed that varicella causes high costs to the healthcare system. Even though less than 1% of varicella patients need to be hospitalized, costs remain high because varicella is so common. Furthermore, if the number of workdays lost are counted as well, then varicella-related costs are even higher.

Cost of illness due to pertussis in adults ≥50 years of age in the United Kingdom.

BACKGROUND: Pertussis is an endemic respiratory tract infection caused by Bordetella pertussis that may affect all individuals from infants to older adults. Pertussis incidence in adults is often underreported and in various countries, including the United Kingdom (UK), there are evidence gaps on pertussis-associated economic burden in the older adult population. We aimed to quantify the economic burden of pertussis in adults aged ≥50 years in the UK. METHODS: A cost-of-illness study was conducted to estimate the cost of pertussis from a societal perspective. We utilized a sum diagnosis cost approach in which costs related to infection with pertussis were included. Medical, patient, and indirect costs were calculated individually and combined to calculate total costs. A framework was developed to assess costs for consecutive age groups from 50-54 years of age to ≥85 years of age. Sensitivity and scenario analyses were used to assess analysis uncertainty. RESULTS: The base-case analysis estimated the total annual economic burden of pertussis to be approximately £238 million (M). This comprised approximately £159 M in indirect costs, £66 M in medical costs, and £13 M in patient costs. Costs for the age group 55-59 years had the highest impact on the economic burden, with approximately £79 M in total annual costs. Visits to general practitioners and nurses were the largest contributors to medical costs (∼£37 M) followed by inpatient visits (∼£21 M). Transportation costs (∼£10 M) were the major patient costs. Productivity loss (∼£71 M) and leisure time loss (∼£72 M) had comparable contributions to annual indirect costs. Sensitivity and scenario analyses suggested that incidence rates, indirect costs, and underreporting estimates had the highest impact on outcomes. CONCLUSION: Total cost of pertussis in the UK among adults ≥50 years of age is substantial and highest for adults 55-59 years of age. Indirect costs were the main contributors to the economic burden.

Reduced reactogenicity of primary vaccination with DT3aP-HBV-IPV/Hib compared with DT2aP-HBV-IPV-Hib among infants: Mathematical projections in six countries.

The hexavalent vaccines DT3aP-HBV-IPV/Hib and DT2aP-HBV-IPV-Hib are routinely used for primary immunization of infants against diphtheria, tetanus, pertussis, hepatitis B virus, poliomyelitis, and Haemophilus influenzae type b. A recent publication showed that after primary immunization with these vaccines, the odds ratios of adverse reactions (ARs) were significantly lower for DT3aP-HBV-IPV/Hib than for DT2aP-HBV-IPV-Hib. Our aim is to understand the impact of the various reactogenicity profiles at country level by comparing the ARs induced by one dose of DT3aP-HBV-IPV/Hib versus DT2aP-HBV-IPV-Hib in the primary infant immunization course. A mathematical projection tool was developed to simulate vaccination of infants with both vaccines in six countries: Austria, the Czech Republic, France, Jordan, Spain, and the Netherlands. Proportions of three local and five systemic ARs of interest for both vaccines were based on findings from a previous meta-analysis of ARs in infants. The absolute risk reductions calculated ranged from 3.0% (95% confidence interval [CI]: 2.8%-3.2%) for "Swelling at the injection site, any grade" to 10.0% (95% CI: 9.5%-10.5%) for "Fever, any grade." The difference in occurrence of the AR "Fever, any grade" between vaccines in 2020 ranged from over 7,000 in Austria to over 62,000 in France. Over 5 years, this would amount to a reduction of over 150,000 ARs in Austria and over 1.4 million ARs in France when using DT3aP-HBV-IPV/Hib instead of DT2aP-HBV-IPV-Hib. In conclusion, the estimated numbers of ARs following hexavalent vaccination in six countries showed that vaccination of infants with DT3aP-HBV-IPV/Hib could lead to fewer ARs than vaccination with DT2aP-HBV-IPV-Hib.

Vaccination of infants against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, and Haemophilus influenzae type b is often performed with combined vaccines against these six diseases. In many countries, these are the first vaccinations received by infants, and potential adverse reactions could affect compliance with future vaccinations. A previous study examined two of the combined vaccines, DT3aP-HBV-IPV/Hib and DT2aP-HBV-IPV-Hib, and showed that local adverse reactions at the injection site (pain, redness, and swelling) and general adverse reactions (fever, drowsiness, irritability, persistent crying, and lack of appetite) were less common after vaccination with DT3aP-HBV-IPV/Hib than with DT2aP-HBV-IPV-Hib.To understand the impact of this finding at a population level, we compared the adverse reactions caused by the hypothetical administration of the two vaccines under similar conditions. We simulated the vaccination of infants with both vaccines in six countries: Austria, the Czech Republic, France, Jordan, Spain, and the Netherlands.The simulation showed that the DT3aP-HBV-IPV/Hib vaccine could reduce cases of swelling at the injection site by 3% and fever by 10%. For the year 2020, the resulting reduction in the estimated number of fever occurrences would have ranged from over 7,000 in Austria to over 62,000 in France. In total, adverse reactions avoided could hypothetically have ranged from 30,781 in Austria to 269,025 in France. Over 5 years, this could have avoided an estimated number of adverse reactions of over 150,000 in Austria to over 1.4 million in France. In conclusion, such a switch of vaccine could substantially reduce adverse reactions.

Burden of Pertussis in Adults Aged 50 Years and Older: A Retrospective Database Study in England.

INTRODUCTION: Pertussis, a highly infectious respiratory disease caused by Bordetella pertussis, affects people of all ages. Older adults are particularly susceptible to its severe outcomes and complications. METHODS: In this retrospective cohort study, the incidence rate of pertussis among individuals aged ≥ 50 years was assessed during 2009-2018 using Clinical Practice Research Datalink and Hospital Episode Statistics databases, United Kingdom. Health care resource utilisation (HCRU) and direct medical costs (DMCs) were compared between patients with a pertussis diagnosis and propensity score-matched controls (matched on demographic and clinical variables). RESULTS: Among 5,222,860 individuals, 1638 had a pertussis diagnosis (incidence rate: 5.8 per 100,000 person-years; 95% confidence interval 5.5-6.0). Baseline (- 18 to - 6 months) HCRU and DMC were similar among 1480 pertussis patients and 1480 matched controls. However, there were increases in HCRU in the pertussis vs. matched cohort around the pertussis diagnosis (from months - 6 to - 1 to 5-11). The most notable increases (pertussis vs. controls) were in the rates of general practitioner (GP)/nurse visits (4.7-fold), clinical assessments (4.1-fold), and accident and emergency visits (3.0-fold) during the month before diagnosis and GP/nurse visits during the 2 months after diagnosis (2.5-fold) (all p < 0.001). DMCs were significantly higher in the pertussis cohort (p < 0.001). Total excess DMC in the pertussis cohort during months - 1 to + 11 was £318 per patient. CONCLUSION: A pertussis diagnosis among adults aged ≥ 50 years resulted in significant increases in HCRU and DMC across several months around diagnosis. These results highlight the need for increased awareness of pertussis infection among adults aged ≥ 50 years and suggest that pertussis booster doses among this population should be considered.

Burden of Pertussis in Individuals with a Diagnosis of Asthma: A Retrospective Database Study in England.

PURPOSE: The impact of pertussis in individuals with asthma is not fully understood. We estimated the incidence, health care resource utilization (HCRU), and direct medical costs (DMC) of pertussis in patients with asthma. PATIENTS AND METHODS: In this retrospective cohort study, the incidence rate of pertussis (identified using diagnostic codes) among individuals aged ≥50 years with an asthma diagnosis was assessed during 2009-2018 using Clinical Practice Research Datalink and Hospital Episode Statistics databases. HCRU and DMC were compared - between patients with diagnoses of asthma and pertussis (asthma+/pertussis+) and propensity score-matched patients with a diagnosis of asthma without pertussis (asthma+/pertussis-) - in the months around the pertussis diagnosis (-6 to +11). RESULTS: Among 687,105 individuals, 346 had a reported pertussis event (incidence rate: 9.6/100,000 person-years of follow-up; 95% confidence interval: 8.6-10.7). HCRU and DMC were assessed among 314 asthma+/pertussis+ patients and 1256 matched asthma+/pertussis- controls. Baseline HCRU was similar in both cohorts, but increases were observed in the asthma+/pertussis+ cohort from -6 to -1 month before to 2-5 months after diagnosis. Rates of accident and emergency visits, general practitioner (GP)/nurse visits, and GP prescriptions were 4.3-, 3.1-, and 1.3-fold, respectively, in the asthma+/pertussis+ vs asthma+/pertussis- cohorts during the month before diagnosis; GP/nurse visit rates were 2.0- and 1.2-fold during 0-2 and 2-5 months after diagnosis, respectively (all p<0.001). DMC was 1.9- and 1.6-fold during the month before and 2 months from diagnosis, respectively, in the asthma+/pertussis+ vs asthma+/pertussis- cohorts (both p<0.001). During months -1 to +11, DMC in the asthma+/pertussis+ cohort was £370 higher than in the asthma+/pertussis- controls. CONCLUSION: A pertussis diagnosis among adults aged ≥50 years with asthma resulted in significant increases in HCRU and DMC across several months around diagnosis, suggesting lengthy diagnosis times and highlighting the need for prevention strategies.

MitraClip therapy in mitral regurgitation: a Markov model for the cost-effectiveness of a new therapeutic option.

Introduction Mitral regurgitation is a heart condition resulting from blood flowing from the left ventricle towards the left atrium, increasing the risk of heart failure and mortality. While surgery can greatly reduce these risks, some patients are not eligible, resulting in medication being their only therapeutic alternative. The MitraClip (Abbot Vascular) is a medical device that is percutaneously implanted and designed to eliminate leaking of the mitral valve. Methods The efficacy of the MitraClip strategy vs medical management was assessed using a 4-state Markov model based on the mitral regurgitation grade (mitral regurgitation grade 0, I/II, and III/IV, and death). At each 1-month cycle, patients were or were not hospitalized. The model analyzed a fictional population of 1000 patients over a 5-year period from a national Health Insurance perspective. The primary end-point was the number of deaths avoided. Data from the EVEREST II High Risk Study patients were used along with a literature review. Results At 5 years, among the 1000 patients, 276 deaths were found to be avoidable with the MitraClip strategy. The incremental cost-effectiveness ratio (ICER) was €93,363 per death avoided. The annual ICER was calculated to take into consideration excess costs resulting from the MitraClip over the first year (€29,984 vs €8557 for the reference strategy) and the reduction of costs in following years (€3122 for MitraClip vs €8557 for reference strategy). Thus, the mean ICER was calculated to be €20,720 per death avoided. Conclusion The MitraClip is a novel alternative therapy for mitral insufficiency in patients ineligible for surgery that may offer a medico-economic advantage.