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Background: To better establish the value of vaccination against influenza viruses, we estimated vaccine-averted influenza illnesses among young children and older adults in Chile, Guyana, and Paraguay., Methods: We gathered country- and target population-specific data on monthly influenza hospitalizations, vaccine coverage, and vaccine effectiveness from surveillance records and immunization registries during 2013-2018. We applied a static compartmental model to estimate differences in the number influenza-associated respiratory disease events (symptomatic non-hospitalized illnesses, medically attended illnesses, hospitalizations) in the presence and absence of influenza vaccination programs., Results: Between 2013 and 2018, vaccinating 68% of children aged 6-23 months in Chile averted an annual mean of 14,617 non-hospitalized, 9,426 medically attended, and 328 hospitalized influenza illnesses; vaccinating 28% of children aged 6-23 months in Paraguay averted 1,115 non-hospitalized, 719 medically attended, and 25 hospitalized influenza illnesses. Vaccinating 59% of older adults in Chile averted an annual mean of 83,429 non-hospitalized, 37,079 medically attended, and 1,390 hospitalized influenza illnesses; vaccinating 36% of older adults in Paraguay averted an annual mean of 3,932 non-hospitalized, 1,748 medically attended, and 66 hospitalized influenza illnesses. In Guyana, a hypothetical campaign vaccinating 30% of children <5 years could have prevented an annual 1,496 non-hospitalized, 971 medically attended, and 10 hospitalized influenza illnesses. Vaccinating 30% of adults ≥65 years could have prevented 568 non-hospitalized, 257 medically attended, and 10 hospitalized influenza illnesses., Conclusions: Influenza vaccination averted tens of thousands of illnesses and thousands of hospitalizations in Chile and Paraguay; influenza vaccination could have had a proportional benefit in Guyana., (© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: We estimate annual viral influenza-associated mild-to-moderate illness, hospitalizations, and deaths in six South American countries (Argentina, Brazil, Chile, Ecuador, Paraguay, and Uruguay) during the 2015-2019 influenza seasons as a first step in evaluating the full value of influenza vaccination in the subregion., Methods: We applied a multiplier methodology using monthly hospital discharge and vital statistics death records, influenza surveillance data, and population projections to estimate mild-to-moderate influenza-associated illness, hospitalizations, and deaths. We estimated the uncertainty bounds based on the 2.5th and 97.5th of the Monte Carlo simulated distributions for the number of cases and obtained the ranges from the minimum value of the 2.5th percentile and the maximum value of the 97.5th percentile., Results: In selected countries with a total population of 307 million people, the yearly influenza-associated burden of disease ranged between 51 and 78 million mild-to-moderate influenza illnesses, between 323,379 and 490,049 hospitalizations, and between 22,662 and 46,971 deaths during the 2015-2019 influenza seasons., Conclusions: Each year, influenza is associated with millions of illnesses, hundreds of thousands of hospitalizations and tens of thousands of deaths in six South American countries, affecting a significant portion of the population. Such findings can be used to estimate the number of illnesses averted through vaccination programs and the cost-benefit of influenza vaccines., (© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

To reduce influenza-associated morbidity and mortality, countries in South America recommend annual influenza vaccination for persons at high risk for severe influenza illness, including young children, persons with preexisting health conditions, and older adults. Interim estimates of influenza vaccine effectiveness (VE) from Southern Hemisphere countries can provide early information about the protective effects of vaccination and help guide Northern Hemisphere countries in advance of their season. Using data from a multicountry network, investigators estimated interim VE against influenza-associated severe acute respiratory illness (SARI) hospitalization using a test-negative case-control design. During March 13-July 19, 2024, Argentina, Brazil, Chile, Paraguay, and Uruguay identified 11,751 influenza-associated SARI cases; on average, 21.3% of patients were vaccinated against influenza, and the adjusted VE against hospitalization was 34.5%. The adjusted VE against the predominating subtype A(H3N2) was 36.5% and against A(H1N1)pdm09 was 37.1%. These interim VE estimates suggest that although the proportion of hospitalized patients who were vaccinated was modest, vaccination with the Southern Hemisphere influenza vaccine significantly lowered the risk for hospitalization. Northern Hemisphere countries should, therefore, anticipate the need for robust influenza vaccination campaigns and early antiviral treatment to achieve optimal protection against influenza-associated complications., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Annette Regan reports receipt of travel support from the International Society for Influenza and Other Respiratory Virus Diseases to attend and present at the 2024 meeting of Options for Control of Influenza, in Brisbane, Australia and from the International Neonatal and Maternal Immunization Symposium to present at the 2024 meeting in San Jose, Costa Rica, and participation on a data safety monitoring board for Moderna’s candidate mRNA RSV vaccine for pregnant women. No other potential conflicts of interest were disclosed.

Cervical cancer is a global health concern and ranks fourth among the most prevalent cancers in women worldwide. Human papillomavirus (HPV) infection is a known precursor of cervical cancer and preventive measures include prophylactic vaccines. This study focused on sexually active Paraguayan women aged 18-25 years, exploring the intersection of HPV vaccination and sexual behavior. Among 254 participants, 40.9% received the Gardasil-4 vaccine, with no significant differences in sexual behavior between the vaccinated and unvaccinated sexually active groups. However, a notable decrease in the prevalence of HPV among the vaccinated women highlights the efficacy of this vaccine in reducing infections. The prevalence of any HPV type was 37.5% in vaccinated participants compared to 56.7% in unvaccinated participants ( p = 0.0026). High-risk HPV types showed a significant difference, with a prevalence of 26.0% in vaccinated women compared with 52.7% in unvaccinated women ( p < 0.001). Although a potential decline in genital warts was observed among the vaccinated individuals, statistical significance ( p = 0.0564) was not reached. Despite the challenges in achieving high vaccination coverage, the observed reduction in HPV prevalence underscores the importance of ongoing monitoring, healthcare professional recommendations, and comprehensive risk management. These findings contribute to dispelling concerns about HPV vaccination influencing sexual behavior, advocating further large-scale research to explore the impact of vaccines on various HPV types and potential cross-protection.

In 2019-2020, dengue virus (DENV) type 4 emerged to cause the largest DENV outbreak in Paraguay's history. This study sought to characterize dengue relative to other acute illness cases and use phylogenetic analysis to understand the outbreak's origin. Individuals with an acute illness (≤7 days) were enrolled and tested for DENV nonstructural protein 1 (NS1) and viral RNA by real-time RT-PCR. Near-complete genome sequences were obtained from 62 DENV-4 positive samples. From January 2019 to March 2020, 799 participants were enrolled: 253 dengue (14 severe dengue, 5.5%) and 546 other acute illness cases. DENV-4 was detected in 238 dengue cases (94.1%). NS1 detection by rapid test was 52.5% sensitive (53/101) and 96.5% specific (387/401) for dengue compared to rRT-PCR. DENV-4 sequences were grouped into two clades within genotype II. No clustering was observed based on dengue severity, location, or date. Sequences obtained here were most closely related to 2018 DENV-4 sequences from Paraguay, followed by a 2013 sequence from southern Brazil. DENV-4 can result in large outbreaks, including severe cases, and is poorly detected with available rapid diagnostics. Outbreak strains seem to have been circulating in Paraguay and Brazil prior to 2018, highlighting the importance of sustained DENV genomic surveillance.

Background: Vaccine effectiveness (VE) estimates vary by population characteristics and circulating variants. North America and Europe have generated many COVID-19 VE estimates but relied heavily on mRNA vaccines. Fewer estimates are available for non-mRNA vaccines and from Latin America. We aimed to estimate the effectiveness of several COVID-19 vaccines in preventing SARS-CoV-2-associated severe acute respiratory infection (SARI) in Paraguay from May 2021 to April 2022., Methods: Using sentinel surveillance data from four hospitals in Paraguay, we conducted a test-negative case-control study to estimate COVID-19 vaccine effectiveness against SARI by vaccine type/brand and period of SARS-CoV-2 variant predominance (Gamma, Delta, Omicron). We used multivariable logistic regression adjusting for month of symptom onset, age group, and presence of ≥1 comorbidity to estimate the odds of COVID-19 vaccination in SARS-CoV-2 test-positive SARI case-patients compared to SARS-CoV-2 test-negative SARI control-patients., Results: Of 4,229 SARI patients, 2,381 (56%) were SARS-CoV-2-positive case-patients and 1,848 (44%) were SARS-CoV-2-negative control-patients. A greater proportion of case-patients (73%; 95% CI: 71-75) than of control-patients (40%; 95% CI: 38-42) were unvaccinated. During the Gamma variant-predominant period, VE estimates for partial vaccination with mRNA vaccines and Oxford/AstraZeneca Vaxzevria were 90.4% (95% CI: 66.4-97.6) and 52.2% (95% CI: 25.0-69.0), respectively. During the Delta variant-predominant period, VE estimates for complete vaccination with mRNA vaccines, Oxford/AstraZeneca Vaxzevria, or Gamaleya Sputnik V were 90.4% (95% CI: 74.3-97.3), 83.2% (95% CI: 67.8-91.9), and 82.9% (95% CI: 53.0-95.2), respectively. The effectiveness of all vaccines declined substantially during the Omicron variant-predominant period., Conclusions: This study contributes to our understanding of COVID-19 VE in Latin America and to global understanding of vaccines that have not been widely used in North America and Europe. VE estimates from Paraguay can parameterize models to estimate the impact of the national COVID-19 vaccination campaign in Paraguay and similar settings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Objectives: This study estimated the 2022 end-of-season influenza vaccine effectiveness (VE) against severe acute respiratory illness (SARI) hospitalization in Chile, Paraguay, and Uruguay., Methods: We pooled surveillance data from SARI cases in 18 sentinel surveillance hospitals in Chile (n = 9), Paraguay (n = 2), and Uruguay (n = 7) from March 16-November 30, 2022. VE was estimated using a test-negative design and logistic regression models adjusted for country, age, sex, presence of ≥1 comorbidity, and week of illness onset. VE estimates were stratified by influenza virus type and subtype (when available) and influenza vaccine target population, categorized as children, individuals with comorbidities, and older adults, defined per countries' national immunization policies., Results: Among the 3147 SARI cases, there were 382 (12.1%) influenza test-positive case patients; 328 (85.9%) influenza case patients were in Chile, 33 (8.6%) were in Paraguay, and 21 (5.5%) were in Uruguay. In all countries, the predominant subtype was influenza A(H3N2) (92.6% of influenza cases). Adjusted VE against any influenza-associated SARI hospitalization was 33.8% (95% confidence interval: 15.3%, 48.2%); VE against influenza A(H3N2)-associated SARI hospitalization was 30.4% (95% confidence interval: 10.1%, 46.0%). VE estimates were similar across target populations., Conclusion: During the 2022 influenza season, influenza vaccination reduced the odds of hospitalization among those vaccinated by one-third. Health officials should encourage influenza vaccination in accordance with national recommendations., Competing Interests: Declarations of Competing Interest The authors have no competing interests to declare., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Dengue is the most common vector-borne viral disease worldwide. Most cases are mild, but some evolve into severe dengue (SD), with high lethality. Therefore, it is important to identify biomarkers of severe disease to improve outcomes and judiciously utilize resources., Methods/principal Findings: One hundred forty-five confirmed dengue cases (median age, 42; range <1-91 years), enrolled from February 2018 to March 2020, were selected from an ongoing study of suspected arboviral infections in metropolitan Asunción, Paraguay. Cases included dengue virus types 1, 2, and 4, and severity was categorized according to the 2009 World Health Organization guidelines. Testing for anti-dengue virus IgM and IgG and serum biomarkers (lipopolysaccharide binding protein and chymase) was performed on acute-phase sera in plate-based ELISAs; in addition, a multiplex ELISA platform was used to measure anti-dengue virus and anti-Zika virus IgM and IgG. Complete blood counts and chemistries were performed at the discretion of the care team. Age, gender, and pre-existing comorbidities were associated with SD vs. dengue with/without warning signs in logistic regression with odds ratios (ORs) of 1.07 (per year; 95% confidence interval, 1.03, 1.11), 0.20 (female; 0.05,0.77), and 2.09 (presence; 1.26, 3.48) respectively. In binary logistic regression, for every unit increase in anti-DENV IgG in the multiplex platform, odds of SD increased by 2.54 (1.19-5.42). Platelet count, lymphocyte percent, and elevated chymase were associated with SD in a combined logistic regression model with ORs of 0.99 (1,000/μL; 0.98,0.999), 0.92 (%; 0.86,0.98), and 1.17 (mg/mL; 1.03,1.33) respectively., Conclusions: Multiple, readily available factors were associated with SD in this population. These findings will aid in the early detection of potentially severe dengue cases and inform the development of new prognostics for use in acute-phase and serial samples from dengue cases., (Copyright: © 2023 Bernal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Although several studies have reported attenuated influenza illness following influenza vaccination, results have been inconsistent and have focused predominantly on adults in the USA. This study aimed to evaluate the severity of influenza illness by vaccination status in a broad range of influenza vaccine target groups across multiple South American countries., Methods: We analysed data from four South American countries (Argentina, Brazil, Chile, and Paraguay) participating in REVELAC-i, a multicentre, test-negative design, vaccine effectiveness network including 41 sentinel hospitals. Individuals hospitalised at one of these centres with severe acute respiratory infection were tested for influenza by real-time RT-PCR, and were included in the analysis if they had complete information about their vaccination status and outcomes of their hospital stay. We used multivariable logistic regression weighted by inverse probability of vaccination and adjusted for antiviral use, duration of illness before admission, and calendar week, to calculate the adjusted odds ratios (aORs) of intensive care unit (ICU) admission and in-hospital death (and combinations of these outcomes) among influenza-positive patients by vaccination status for three target groups: young children (aged 6-24 months), adults (aged 18-64 years) with pre-existing health conditions, and older adults (aged ≥65 years). Survival curves were used to compare length of hospital stay by vaccination status in each target group., Findings: 2747 patients hospitalised with PCR-confirmed influenza virus infection between Jan 1, 2013, and Dec 8, 2019, were included in the study: 649 children (70 [10·8%] fully vaccinated, 193 [29·7%] partially vaccinated) of whom 87 (13·4%) were admitted to ICU and 12 (1·8%) died in hospital; 520 adults with pre-existing medical conditions (118 [22·7%] vaccinated), of whom 139 (26·7%) were admitted to ICU and 55 (10·6%) died in hospital; and 1578 older adults (609 [38·6%] vaccinated), of whom 271 (17·2%) were admitted to ICU and 220 (13·9%) died in hospital. We observed earlier discharge among partially vaccinated children (adjusted hazard ratio 1·14 [95% CI 1·01-1·29]), fully vaccinated children (1·24 [1·04-1·47]), and vaccinated adults with pre-existing medical conditions (1·78 [1·18-2·69]) compared with their unvaccinated counterparts, but not among vaccinated older adults (0·82 [0·65-1·04]). Compared with unvaccinated individuals, lower odds of ICU admission were found for partially vaccinated children (aOR 0·64 [95% CI 0·44-0·92]) and fully vaccinated children (0·52 [0·28-0·98]), but not for adults with pre-existing conditions (1·25 [0·93-1·67]) or older adults (0·88 [0·72-1·08]). Lower odds of in-hospital death (0·62 [0·50-0·78]) were found in vaccinated versus unvaccinated older adults, with or without ICU admission, but did not differ significantly in partially vaccinated (1·35 [0·57-3·20]) or fully vaccinated young children (0·88 [0·16-4·82]) or adults with pre-existing medical conditions (1·09 [0·73-1·63]) compared with the respective unvaccinated patient groups., Interpretation: Influenza vaccination was associated with illness attenuation among those hospitalised with influenza, although results differed by vaccine target group. These findings might suggest that attenuation of disease severity might be specific to certain target groups, seasons, or settings., Funding: US Centers for Disease Control and Prevention., Translations: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Influenza illness burden is substantial, particularly among young children, older adults, and those with underlying conditions. Initiatives are underway to develop better global estimates for influenza-associated hospitalizations and deaths. Knowledge gaps remain regarding the role of influenza viruses in severe respiratory disease and hospitalizations among adults, particularly in lower-income settings., Methods and Findings: We aggregated published data from a systematic review and unpublished data from surveillance platforms to generate global meta-analytic estimates for the proportion of acute respiratory hospitalizations associated with influenza viruses among adults. We searched 9 online databases (Medline, Embase, CINAHL, Cochrane Library, Scopus, Global Health, LILACS, WHOLIS, and CNKI; 1 January 1996-31 December 2016) to identify observational studies of influenza-associated hospitalizations in adults, and assessed eligible papers for bias using a simplified Newcastle-Ottawa scale for observational data. We applied meta-analytic proportions to global estimates of lower respiratory infections (LRIs) and hospitalizations from the Global Burden of Disease study in adults ≥20 years and by age groups (20-64 years and ≥65 years) to obtain the number of influenza-associated LRI episodes and hospitalizations for 2016. Data from 63 sources showed that influenza was associated with 14.1% (95% CI 12.1%-16.5%) of acute respiratory hospitalizations among all adults, with no significant differences by age group. The 63 data sources represent published observational studies (n = 28) and unpublished surveillance data (n = 35), from all World Health Organization regions (Africa, n = 8; Americas, n = 11; Eastern Mediterranean, n = 7; Europe, n = 8; Southeast Asia, n = 11; Western Pacific, n = 18). Data quality for published data sources was predominantly moderate or high (75%, n = 56/75). We estimate 32,126,000 (95% CI 20,484,000-46,129,000) influenza-associated LRI episodes and 5,678,000 (95% CI 3,205,000-9,432,000) LRI hospitalizations occur each year among adults. While adults <65 years contribute most influenza-associated LRI hospitalizations and episodes (3,464,000 [95% CI 1,885,000-5,978,000] LRI hospitalizations and 31,087,000 [95% CI 19,987,000-44,444,000] LRI episodes), hospitalization rates were highest in those ≥65 years (437/100,000 person-years [95% CI 265-612/100,000 person-years]). For this analysis, published articles were limited in their inclusion of stratified testing data by year and age group. Lack of information regarding influenza vaccination of the study population was also a limitation across both types of data sources., Conclusions: In this meta-analysis, we estimated that influenza viruses are associated with over 5 million hospitalizations worldwide per year. Inclusion of both published and unpublished findings allowed for increased power to generate stratified estimates, and improved representation from lower-income countries. Together, the available data demonstrate the importance of influenza viruses as a cause of severe disease and hospitalizations in younger and older adults worldwide., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: H.N.: Grants from the Foundation for Influenza Epidemiology, grants from Innovative Medicines Initiative, grants from the WHO, personal fees from Bill and Melinda Gates Foundation, grants and personal fees from Sanofi, grants from National Institute of Health Research, personal fees from Janssen and personal fees from AbbVie, outside the submitted work. The remaining authors have declared that no competing interests exist.

Background: In 2013, the Pan American Health Organization established a multi-site, multi-country network to evaluate influenza vaccine effectiveness (VE). We pooled data from five consecutive seasons in five countries to conduct an analysis of southern hemisphere VE against laboratory-confirmed influenza hospitalizations in young children and older adults., Methods: We used a test-negative design to estimate VE against laboratory-confirmed influenza in hospitalized young children (aged 6─24 months) and older adults (aged ≥60 years) in Argentina, Brazil, Chile, Colombia, and Paraguay. Following country-specific influenza surveillance protocol, hospitalized persons with severe acute respiratory infections (SARI) at 48 sentinel hospitals (March 2013-December 2017) were tested for influenza virus infection by rRT-PCR. VE was estimated for young children and older adults using logistic random effects models accounting for cluster (country), adjusting for sex, age (months for children, and age-in-year categories for adults), calendar year, country, preexisting conditions, month of illness onset and prior vaccination as an effect modifier for the analysis in adults., Results: We included 8426 SARI cases (2389 children and 6037 adults) in the VE analyses. Among young children, VE against SARI hospitalization associated with any influenza virus was 43% (95%CI: 33%, 51%) for children who received two doses, but was 20% (95%CI: -16%, 45%) and not statistically significant for those who received one dose in a given season. Among older adults, overall VE against SARI hospitalization associated with any influenza virus was 41% (95%CI: 28%, 52%), 45% (95%CI: 34%, 53%) against A(H3N2), 40% (95%CI: 18%, 56%) against A(H1N1)pdm09, and 20% (95%CI: -40%, 54%) against influenza B viruses., Conclusions: Our results suggest that over the five-year study period, influenza vaccination programs in five South American countries prevented more than one-third of laboratory confirmed influenza-associated hospitalizations in young children receiving the recommended two doses and vaccinated older adults., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Despite having influenza vaccination policies and programs, countries in the Americas underutilize seasonal influenza vaccine, in part because of insufficient evidence about severe influenza burden. We aimed to estimate the annual burden of influenza-associated respiratory hospitalizations in the Americas., Methods: Thirty-five countries in the Americas with national influenza surveillance were invited to provide monthly laboratory data and hospital discharges for respiratory illness (International Classification of Diseases 10th edition J codes 0-99) during 2010-2015. In three age-strata (<5, 5-64, and ≥65 years), we estimated the influenza-associated hospitalizations rate by multiplying the monthly number of respiratory hospitalizations by the monthly proportion of influenza-positive samples and dividing by the census population. We used random effects meta-analyses to pool age-group specific rates and extrapolated to countries that did not contribute data, using pooled rates stratified by age group and country characteristics found to be associated with rates., Results: Sixteen of 35 countries (46%) contributed primary data to the analyses, representing 79% of the America's population. The average pooled rate of influenza-associated respiratory hospitalization was 90/100,000 population (95% confidence interval 61-132) among children aged <5 years, 21/100,000 population (13-32) among persons aged 5-64 years, and 141/100,000 population (95-211) among persons aged ≥65 years. We estimated the average annual number of influenza-associated respiratory hospitalizations in the Americas to be 772,000 (95% credible interval 716,000-829,000)., Conclusions: Influenza-associated respiratory hospitalizations impose a heavy burden on health systems in the Americas. Countries in the Americas should use this information to justify investments in seasonal influenza vaccination-especially among young children and the elderly., Competing Interests: The authors have declared that no competing interests exist.

Objective: There are limited published data about the circulation of influenza B/Victoria and B/Yamagata in Latin America and the Caribbean (LAC) and most countries have a vaccine policy that includes the use of the trivalent influenza vaccine. We analyzed influenza surveillance data to inform decision-making in LAC about prevention strategies, such as the use of the quadrivalent influenza vaccine., Methods: There are a total of 28 reference laboratories and National Influenza Centers in LAC that conduct influenza virologic surveillance according to global standards, and on a weekly basis upload their surveillance data to the open-access World Health Organization (WHO) platform FluNet. These data include the number of specimens tested for influenza and the number of specimens positive for influenza by type, subtype and lineage, all by the epidemiologic week of specimen collection. We invited these laboratories to provide additional epidemiologic data about the hospitalized influenza B cases. We conducted descriptive analyses of patterns of influenza circulation and characteristics of hospitalized cases. We compared the predominant B lineage each season to the lineage in the vaccine applied, to determine vaccine mismatch. A Chi-square and Wilcoxan statistic were used to assess the statistical significance of differences in proportions and medians at the P<0.05 level., Findings: During 2010-2017, the annual number of influenza B cases in LAC was ~4500 to 7000 cases. Since 2011, among the LAC-laboratories reporting influenza B lineage using molecular methods, both B/Victoria and B/Yamagata were detected annually. Among the hospitalized influenza B cases, there were statistically significant differences observed between B/Victoria and B/Yamagata cases when comparing age and the proportion with underlying co-morbid conditions and with history of oseltamivir treatment (P<0.001). The proportion deceased among B/Victoria and B/Yamagata hospitalized cases did not differ significantly. When comparing the predominant influenza B lineage detected, as part of surveillance activities during 63 seasons among 19 countries, to the lineage of the influenza B virus included in the trivalent influenza vaccine used during that season, there was a vaccine mismatch noted during 32% of the seasons analyzed., Conclusions: Influenza B is important in LAC with both B/Victoria and B/Yamagata circulating annually in all sub regions. During approximately one-third of the seasons, an influenza B vaccine mismatch was identified. Further analyses are needed to better characterize the medical and economic burden of each influenza B lineage, to examine the potential cross-protection of one vaccine lineage against the other circulating virus lineage, and to determine the potential impact and cost-effectiveness of using the quadrivalent vaccine rather than the trivalent influenza vaccine., Competing Interests: The authors have declared that no competing interests exist.

Background: The global burden of pediatric severe respiratory illness is substantial, and influenza viruses contribute to this burden. Systematic surveillance and testing for influenza among hospitalized children has expanded globally over the past decade. However, only a fraction of the data has been used to estimate influenza burden. In this analysis, we use surveillance data to provide an estimate of influenza-associated hospitalizations among children worldwide., Methods and Findings: We aggregated data from a systematic review (n = 108) and surveillance platforms (n = 37) to calculate a pooled estimate of the proportion of samples collected from children hospitalized with respiratory illnesses and positive for influenza by age group (<6 mo, <1 y, <2 y, <5 y, 5-17 y, and <18 y). We applied this proportion to global estimates of acute lower respiratory infection hospitalizations among children aged <1 y and <5 y, to obtain the number and per capita rate of influenza-associated hospitalizations by geographic region and socio-economic status. Influenza was associated with 10% (95% CI 8%-11%) of respiratory hospitalizations in children <18 y worldwide, ranging from 5% (95% CI 3%-7%) among children <6 mo to 16% (95% CI 14%-20%) among children 5-17 y. On average, we estimated that influenza results in approximately 374,000 (95% CI 264,000 to 539,000) hospitalizations in children <1 y-of which 228,000 (95% CI 150,000 to 344,000) occur in children <6 mo-and 870,000 (95% CI 610,000 to 1,237,000) hospitalizations in children <5 y annually. Influenza-associated hospitalization rates were more than three times higher in developing countries than in industrialized countries (150/100,000 children/year versus 48/100,000). However, differences in hospitalization practices between settings are an important limitation in interpreting these findings., Conclusions: Influenza is an important contributor to respiratory hospitalizations among young children worldwide. Increasing influenza vaccination coverage among young children and pregnant women could reduce this burden and protect infants <6 mo., Competing Interests: We have read the journal's policy and have the following competing interests: DEN has participated on an influenza advisory board for Novartis. RB works with all major manufacturers of influenza vaccines in an advisory capacity, as a researcher on vaccines and as presenter of academic info at conferences, receiving support to travel and attend such conferences. The authors have declared that no other competing interests exist.