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We conducted a dose-finding phase 2 study of the HilleVax bivalent virus-like particle (VLP) vaccine candidate (HIL-214) in two cohorts of children, 6-≤12 months and 1-≤4 years of age (N = 120 per cohort), in Panama and Colombia (ClinicalTrials.gov, identifier NCT02153112). On Day 1, children randomized to one of the four equal groups received intramuscular injections of four different HIL-214 formulations containing 15/15, 15/50, 50/50, or 50/150 μg of GI.1/GII.4c genotype VLPs and 0.5 mg Al(OH) 3 . On Day 29, half the children in each group received a second vaccination (N = 60), while the other half received saline placebo injections to maintain the blind. VLP-specific ELISA Pan-Ig and histo-blood group binding antigen-blocking antibodies (HBGA) were measured on Days 1, 29, 57 and 210. On Day 29, after one dose, there were large Pan-Ig and HBGA responses in both age cohorts with some indication of dose-dependence, and higher geometric mean titers (GMT) in the older children. A further increase in titers was observed 28 days after a second dose in the 6-≤12-month-old groups, but less so in the 1-≤4-year-old groups; GMTs at Day 57 were broadly similar across doses and in both age groups. GMTs of Pan-Ig and HBGA persisted above baseline up to Day 210. All formulations were well tolerated with mostly mild-to-moderate transient solicited adverse events reported by parents/guardians, and no vaccine-related serious adverse events occurred. Further development of HIL-214 is warranted to protect the most susceptible young children against norovirus.

Varicella is an acute, highly contagious disease in susceptible individuals and is preventable through vaccination. This study aimed to determine the impact of varicella vaccination on hospitalizations and complications at a pediatric reference hospital in Panama before and after the vaccine introduction. This descriptive ecological study analyzed clinical records of patients diagnosed with varicella through a retrospective and interrupted time series analysis. An autoregressive integrated moving average model was built to compare the incidence rates observed after vaccination with those expected rates derived from the model. A statistical model was fitted to the observed interrupted time series data by regression and used to predict future trends. The mean difference in varicella hospital discharges before and after the introduction of the varicella vaccine was 47%. The rate of hospitalizations for varicella decreased to 52.3%. A declining trend in varicella hospitalizations was observed from 2015 after vaccine introduction in 2014. Complications in vaccinated patients were secondary skin and soft tissue infection, possibly due to bacterial superinfection. The impact of varicella vaccination on reducing varicella hospital discharges reported at a pediatric reference hospital in Panama was confirmed.

In 2010, a 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) was introduced in the Brazilian national immunization program; the 3 + 1 dose schedule was replaced by a 2 + 1 dose schedule in 2016. This systematic review presents the latest published evidence (2015-2020) on the impact after 10-year use of PHiD-CV in Brazil from a total of 29 publications. Overall, the PHiD-CV program had a positive impact on the morbidity and mortality associated with invasive pneumococcal disease (IPD), pneumonia and acute otitis media (AOM) in children <5 years-old. A reduction in the vaccine-type invasive disease was observed in all-ages; suggesting indirect protection unvaccinated older children and adults. The occurrence of non-vaccine type disease was evidenced in some studies. Higher vaccination coverage is required at national and state level for sustained population impact. Given the change in the vaccination schedule and the dynamics of pneumococcal disease epidemiology, continuous surveillance is warranted.GSK Study identifier: HO-18-19438.

In Colombia, pneumococcal conjugate vaccines (PCVs) were implemented into the infant universal mass vaccination program in a stepwise manner; PCV-7 between 2009 and 2011 in different geographic regions/cities, with nationwide introduction of a 10-valent vaccine (PHiD-CV) in 2012. We aimed to describe trends in all-cause pneumonia mortality and overall mortality, and in the incidence of all-cause pneumonia and otitis media (OM) in Colombian children <2 y (y = years) of age, before and after PCV introduction. We obtained mortality and incidence data, nationally and for five major cities (Bogota, Medellin, Barranquilla, Cali and Cartagena) from 2005-2016 and 2008-2016, respectively, comparing mortality and incidence proportions in the post-PCV introduction period with those in the pre-PCV period. Overall mean reductions in all-cause pneumonia mortality was observed in the post-PCV period nationally (48.8%; 95%CI: 45.5-51.8%) and in four cities including Bogota (77.1%; 71.1-81.8%) and Medellin (56.4%; 44.1-65.9%); no substantial reduction was observed in Cartagena. Similar findings were observed for overall mortality. Reductions in all-cause pneumonia incidence were observed in Bogota (66.0%; 65.5-66.6%), Medellin (40.6%; 39.3-41.9%) and Cartagena (15.0%; 11.2-18.6%), while incidence increased in Barranquilla (78.5%; 68.4-89.2%) and Cali (125.5%; 119.2-132.0%). All-cause OM incidence fell in Medellin and Bogota (42.1-51.1%) but increased (95.8%) in Barranquilla. In conclusion, overall reductions in disease outcomes were observed following PCV introduction in most cities and nationwide. Decreasing trends in outcomes were observed prior to PCV introduction, and limited data points and data reporting issues may have influenced our results. (ClinicalTrials.gov: NCT02567747).

Background: National pediatric vaccination programs have been introduced in Latin America (LatAm) to reduce the burden of diseases due to pathogens such as rotavirus, Haemophilus influenzae type b (Hib) and pneumococcus. Vaccination health benefits may extend to unvaccinated populations by reducing pathogen transmission. Understanding herd effect is important for implementation and assessment of vaccination programs. The objective was to conduct a systematic review of published epidemiological evidence of herd effect with Hib, rotavirus and pneumococcal conjugate vaccines (PCV) in LatAm., Methods: Searches were conducted in PubMed, Virtual Health Library (VHL), SciELO and SCOPUS databases, for studies reporting data on herd effect from Hib, rotavirus and PCV vaccination in LatAm, without age restriction. Searches were limited to articles published in English, Spanish or Portuguese (1990-2016). After screening and full-text review, articles meeting the selection criteria were included to be critically appraised following criteria for observational and interventional studies. The presence of a herd effect was defined as a significant decrease in incidence of disease, hospitalization, or mortality., Results: 3,465 unique articles were identified, and 23 were included (Hib vaccine n = 5, PCV n = 8, rotavirus vaccine n = 10). Most studies included children and/or adolescents (age range varied between studies). Studies in adults, including older adults (aged > 65 years), were limited. Few studies reported statistically significant reductions in disease incidence in age groups not targeted for vaccination. Hib-confirmed meningitis hospitalization decreased in children but herd effect could not be quantified. Some evidence of herd effect was identified for PCV and rotavirus vaccine in unvaccinated children. Evidence for herd effects due to PCV in adults was limited., Conclusion: After introduction of Hib, PCV and rotavirus vaccination in LatAm, reductions in morbidity/mortality have been reported in children not targeted for vaccination. However, due to methodological limitations (e.g. short post-vaccination periods and age range studied), there is currently insufficient evidence to quantify the herd effect in adult populations. More research and higher quality surveillance is needed to characterize herd effect of these vaccines in LatAm.

Worldwide, rotavirus infection has been a leading cause of severe diarrhea morbidity and mortality. Two rotavirus vaccines have been used in the National Immunization Program (NIP) in Mexico; two-dose Rotarix from 2006 to 2011 and three-dose RotaTeq since 2011. This study assessed coverage (receiving at least one dose or full dose series) in eligible infants, compliance (% completing dose series and % completing series on schedule) in eligible infants vaccinated with Rotarix (2010) versus RotaTeq (2012), using Mexican Social Security Institute data nationwide and by regions. In 2010, 80.7% received at least one dose of Rotarix , 75.6% received both doses and 57.0% received both doses on schedule. In 2012, 85.7% received at least one dose of RotaTeq , 61.0% received all three doses and 43.2% received all three doses on schedule. More eligible infants received all doses with Rotarix versus RotaTeq (p < 0.001). Among infants vaccinated with Rotarix versus RotaTeq , 93.7% versus 71.1% completed full series (p < 0.001), and 75.5% versus 70.9% completed full series on schedule (p = 0.105), respectively. The full series coverage and compliance decreased in all regions with RotaTeq compared with Rotarix . In conclusion, rotavirus vaccination has successfully reduced morbidity and mortality in children under 5 years in Mexico. This study found significant differences in full series coverage and compliance among infants and a higher proportion of completed scheduled at an earlier age in Mexico when comparing a two-dose vaccine in 2010 with a three-dose vaccine in 2012. Such differences might need to be taken into consideration to maximize NIP benefits, including early protection of the rotavirus vaccination program.

Objectives: To estimate hepatitis B virus (HBV) seroprevalence from natural infection or vaccination in 10-25-year-olds in Mexico, using the 2012 National Health and Nutrition Survey (ENSANUT)., Methods: Randomly selected serum samples (1,581) from adolescents and young adults, representative of 38,924,584 Mexicans, were analyzed to detect hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs) and hepatitis B core antibody (anti-HBc). Weighted HBV seroprevalence in the Mexican population and association with sociodemographic variables were calculated., Results: Overall weighted seroprevalence from natural infection (positive for anti-HBs and anti-HBc) was 0.23% (95% confidence interval [95% CI] 0.10-0.52). No HBsAg was detected, indicating no acute or chronic infection. Vaccine-derived immunity (positive ≥ 10.0 mIU/ml for anti-HBs and negative to anti-HBc) was 44.7% (95% CI: 40.2-49.4) overall; lower in persons aged 20-25 years (40.83%) than in persons aged 10-19 years (47.7%). Among the population analyzed, 54.2% (95% CI: 49.6-58.8) were seronegative to HBV (negative for all three markers) and no sociodemographic risk factors were identified., Conclusions: HBV seroprevalence from natural infection was low. Vaccination-induced immunity was higher among Mexican adolescents than young adults, possibly due to vaccination policies since 1999.

Colombia introduced mass pneumococcal conjugate vaccination at the end of 2011. Using 2005-2015 surveillance data, we conducted a retrospective interrupted time-series analysis. A significant trend towards reduced monthly was observed in the post-vaccination period (2012-2015) compared with the expected rate, reaching in 2015 a reduction of 90.5% of pneumococcal meningitis. This trend was not observed for control diseases.

Varicella-zoster virus causes varicella (chicken-pox), mainly in young children. Most cases are mild but serious complications can occur, resulting in significant morbidity and mortality. The objective of this study was to estimate the cost burden of varicella hospitalizations in two pediatric reference hospitals in Mexico. This retrospective observational study collected data on patients aged <18 years admitted to two third-level referral hospitals in Mexico. Cases were identified from hospital records using International Classification of Diseases Ninth Revision (ICD-9) codes 052 Chickenpox, or Tenth Revision (ICD-10) codes B01 Varicella (chickenpox). Data on demographic and clinical characteristics and resource use were collected from hospital records. Costs for hospital stay and interventions were obtained from the Mexican Institute for Social Security for 2015 and updated to 2017 costs. A total of 172 hospitalized varicella clinically-confirmed cases and 121 varicella- contacts (with epidemiological linkage to a clinically-confirmed case) were included. Thirty eight of the 172 cases (22.0%) experienced complications. There were no deaths. The median duration of hospitalization was 12 days for cases and 23 days for contacts. The median hospitalization cost was MXN 82,572 (USD 4,434) per case, and MXN 89,453 (USD 4,804) per contact. Although considered a mild disease, varicella was associated with a substantial cost burden in two Mexican third-level referral hospitals.

Despite vaccination programs, influenza still represents a significant disease burden in Mexico. We conducted an observational, retrospective analysis to better understand the epidemiological situation of the influenza virus in Mexico. Analysis of the seasonal patterns of influenza A and B were based on the Directorate General of Epidemiology dataset of influenza-like illness(ILI), and severe acute respiratory infection(SARI) that were recorded between January 2010 and December 2013. Our objectives were 1) to describe influenza A and B activity, by age group, and subtype and, 2) to analyze the number of laboratory-confirmed cases presenting with ILI by influenza type, the regional distribution of influenza, and its clinical features. Three periods of influenza activity were captured: August 2010-January 2011, December 2011-March 2012, and October 2012-March 2013. Cases were reported throughout Mexico, with 50.3% (n = 10,320) of cases found in 18-49 year olds. Over the entire capture period, a total of 76,085 ILI/SARI episodes had swab samples analyzed for influenza, 27% were positive. During the same period, influenza A cases were higher in the 18-49 years old, and influenza B cases in both 5-17 and 18-49 age groups. Peak activity occurred in January 2012 (n = 4,159) and December 2012 (n = 348) for influenza A and B respectively. This analysis confirms that influenza is an important respiratory pathogen for children and adults in Mexico despite vaccination recommendations. School-age children and adolescents were more prone to influenza B infection; while younger adults were susceptible to both influenza A and B viruses. Over the seasons, influenza A and B co-circulated.

This systematic review evaluated the epidemiology of community-acquired pneumonia in children <6 y of age within 90 developing and newly industrialized countries. Literature searches (1990-2011), based on MEDLINE, EMBASE, Cochrane, CAB Global Health, WHO, UNICEF, country-specific websites, conferences, health-technology-assessment agencies, and the reference lists of included studies, yielded 8,734 records; 62 of 340 studies were included in this review. The highest incidence rate among included studies was 0.51 episodes/child-year, for children <5 y of age in Bangladesh. The highest prevalence was in Chinese children <6 months of age (37.88%). The main bacterial pathogens were Streptococcus pneumoniae, Haemophilus influenzae and Mycoplasma pneumoniae and the main viral pathogens were respiratory syncytial virus, adenovirus and rhinovirus. Community-acquired pneumonia remains associated with high rates of morbidity and mortality. Improved and efficient surveillance and documentation of the epidemiology and burden of community-acquired pneumonia across various geographical regions is warranted.

As infants suffer significant morbidity and mortality due to norovirus-related acute gastroenteritis (AGE), we assessed four formulations of the bivalent virus-like particle (VLP) vaccine candidate (HIL-214) in Panamanian and Colombian infants. 360 infants aged 6 weeks to 5 months were randomly allocated to 8 groups to receive three doses of HIL-214 or two doses of HIL-214 and one dose of placebo (Days 1, 56 and 112), where HIL-214 doses contained 15/15, 15/50, 50/50 or 50/150 μg of GI.1/GII.4c genotype VLPs and 0.5 mg Al(OH) 3 . Solicited injection-site and systemic adverse events (AE) were collected within 7 days after each dose, unsolicited AEs were collected within 28 days after each, and serious AEs throughout the study. Pan-Ig and histoblood group antigen-blocking antibodies (HBGA) were measured on Days 1, 56, 84, and 140. All formulations were well-tolerated causing mainly mild-to-moderate transient solicited AEs, most frequently local pain and irritability/fussiness, but no vaccine-related serious AEs. Two doses of each formulation induced high titers of high avidity Pan-Ig and also HBGA antibodies; a third dose increased titers against both antigens and the avidity of Pan-Ig antibodies against GII.4c but not against GI.1. Two and three doses of HIL-214 were well-tolerated and induced potent immune responses at 4-6 months of age supporting further clinical assessment to protect against norovirus-related AGE.

Rotavirus (RV) is the most common etiological agent causing acute gastroenteritis (GE) in children aged <5 years. This cross-sectional, hospital-based surveillance study (NCT01201252) was designed to investigate RVGE disease burden. It was conducted from July 2009-July 2010 at 3 referral hospitals in the United Arab Emirates (UAE). Children who had been hospitalized for acute GE were enrolled with informed consent. Stool samples were tested for RV using enzyme immunoassay and RV-positive samples were further typed using reverse transcriptase-polymerase chain reaction and reverse hybridization to determine the G and P types. GE data were collected from medical charts and GE severity was assessed through clinical examination. Treatment and outcome were prospectively recorded. Among 6323 children hospitalized due to any reason, 771 (12.2%) presented acute GE and were enrolled, of whom 758 (98.3%) were included in the final analysis. Acute GE and RVGE accounted for 12.0% (758/6323) and 6.0% (381/6323) of all hospitalizations, respectively. RVGE accounted for 50.3% (381/758) of GE hospitalizations and predominantly affected, children younger than 2 years (66.1%; 252/381). The severity of GE before hospitalization was significantly associated with RV-positive status (P = 0.0031). The majority (>95%) of children received intravenous hydration during hospitalization. RVGE occurred throughout the year, with a subtle winter peak in February 2010 (63.6%; 56/88). G1WTP[8]WT was the most commonly detected RV strain (56.3%) in 268 analyzed samples. RV was a major cause of GE-hospitalizations in children under 5 years in the UAE; the highest number of RVGE cases was observed in children younger than 2 years.

Hepatitis A virus (HAV) remains a public health concern worldwide contributing to significant morbidity in developed and developing countries. This cross-sectional database study estimated the overall HAV seroprevalence and the seroprevalence by gender, age, region and socioeconomic status in Mexico. Between January and October 2010, serum samples collected during the National Health and Nutrition survey (ENSANUT 2006) were obtained from subjects aged 1-95 y. Subjects' gender, age, geographical region and socioeconomic status were extracted from the survey and compiled into a subset database by the Mexican National Institute of Public Health. Anti-HAV antibodies were measured using a chemiluminescent immunoassay. A total of 3658 subjects were included in the according-to-protocol cohort. Overall, the HAV seroprevalence was 84.2%. The HAV seroprevalence rates were similar between females (86.1%) and males (82.2%). The percentage of subjects seropositive for anti-HAV antibodies was highest in adults aged ≥ 20 y (96.9%), followed by adolescents aged 10-19 y (80.1%) and lowest in children aged 1-9 y (45.0%) (p < 0.0001). Regionally, the highest HAV seroprevalence rate was observed in the South (88.8%) followed by Central and Northern Mexico and Mexico City (p = 0.02). The HAV seroprevalence was similar between subjects of high socioeconomic (90.1%) status and of low socioeconomic status (86.6%). This study confirms the intermediate HAV endemicity in Mexico. Cost-effectiveness studies are necessary to evaluate the inclusion of an effective hepatitis A vaccine from a population-based perspective in addition to continuous efforts to improve hygiene and sanitation that have a substantial impact on the disease burden.