Safety and Immunogenicity of an Inactivated Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine in a Subgroup of Healthy Adults in Chile.

BACKGROUND: The development of effective vaccines against coronavirus disease 2019 is a global priority. CoronaVac is an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine with promising safety and immunogenicity profiles. This article reports safety and immunogenicity results obtained for healthy Chilean adults aged ≥18 years in a phase 3 clinical trial. METHODS: Volunteers randomly received 2 doses of CoronaVac or placebo, separated by 2 weeks. A total of 434 volunteers were enrolled, 397 aged 18-59 years and 37 aged ≥60 years. Solicited and unsolicited adverse reactions were registered from all volunteers. Blood samples were obtained from a subset of volunteers and analyzed for humoral and cellular measures of immunogenicity. RESULTS: The primary adverse reaction in the 434 volunteers was pain at the injection site, with a higher incidence in the vaccine than in the placebo arm. Adverse reactions observed were mostly mild and local. No severe adverse events were reported. The humoral evaluation was performed on 81 volunteers. Seroconversion rates for specific anti-S1-receptor binding domain (RBD) immunoglobulin G (IgG) were 82.22% and 84.44% in the 18-59 year age group and 62.69% and 70.37% in the ≥60 year age group, 2 and 4 weeks after the second dose, respectively. A significant increase in circulating neutralizing antibodies was detected 2 and 4 weeks after the second dose. The cellular evaluation was performed on 47 volunteers. We detected a significant induction of T-cell responses characterized by the secretion of interferon-γ (IFN-γ) upon stimulation with Mega Pools of peptides from SARS-CoV-2. CONCLUSIONS: Immunization with CoronaVac in a 0-14 schedule in Chilean adults aged ≥18 years is safe, induces anti-S1-RBD IgG with neutralizing capacity, activates T cells, and promotes the secretion of IFN-γ upon stimulation with SARS-CoV-2 antigens.

[Statement from the Immunization Committee of the Chilean Infectious Diseases Society in reference to vaccine refusal and mandatory policy on vaccination]. / Posición del Comité Consultivo de Inmunizaciones de la Sociedad Chilena de Infectología en relación a los cuestionamientos de las vacunas y su obligatoriedad.

Although vaccines have had a tremendous impact in public health they are questioned by certain groups that consider them unnecessary or unsafe and argue in favor of the right to decide to be vacci nated or not. However vaccines must have special considerations because unlike other medical deci sions, not vaccinating has consequences not only for the individual but also for other members of the community. Immunizing a high proportion of the population limits the circulation of an infectious agent attaining what is called community or herd immunity that protects the susceptible members of the group. For this reason many countries consider vaccination mandatory as a responsibility of every citizen. This committee agrees with this view but thinks other strategies should be implemented as well, such as special educational efforts for the public and parents addressing benefits and real risks of vaccinating. Also health care professionals should be trained in vaccines. The notification system for adverse events currently available should be improved and be more accessible. Persons truly affected by adverse events due to vaccination should receive on time responses and be offered psychological and financial support. Finally all stakeholders should make coordinated efforts to work together to deliver messages that answer concerns on vaccines and bring confidence back to the public.

[Pneumococcal vaccines in children: an update]. / Vacunas anti-neumocóccicas en población pediátrica: actualización.

Conjugated pneumococal vaccines had a notable impact on prevention of invasive pneumococcal disease (IPD) in vacccinated and non vaccinated (herd immunity) populations. In Chile a 10 valent conjugated vaccine (PCV10) was introduced in the Nacional Immunization Program (NIP) in 2011, initially in a 3+1 schedule at 2, 4, 6 and 12 months of age, and since 2012 in a 2+1 schedule (2, 4 and 12 months). In prematures schedule 3+1 was maintained. No catch up or high risk groups vaccination strategies were used. The inclusion of PCV10 has reduced the rates of IPD; 66% in infants less than 12 months old and a 60% in 12-24 months old. After 3 years of the introduction of PCV10, no herd immunity has been seen. Serotype replacement shows an increase of ST 3 but not ST19A. Surveillance shows that another vaccine with 13 serotypes (PCV13) would cover an additional 5 to 10% of cases. The nule herd immunity and more extense coverage of PCV13, suggests that NIP should switch from PCV10 to PCV13.

[Impact of an automated rapid MRSA/VRE identification technique in the surveillance of patients transferred from other medical centers]. / Impacto de una técnica automatizada rápida en la identificación de SAMR/ERV en pacientes trasladados desde otros centros hospitalarios.

INTRODUCTION: Identification of patients with methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococci (VRE) is essential to limit the spread of these agents, through the use of isolation and contact precautions. Traditional microbiology has a long turn around time (3-5 days) extending the time of isolation, increasing complexity and cost of these patients. OBJECTIVES: To implement a new real time polymerase chain reaction (PCR) GeneXpert R for SAMR and VRE detection. To compare costs and turn around time of PCR versus traditional cultures. METHODS: Two periods were compared, in the first, traditional microbiology (standard group) was used, and in the second, only PCR was used (PCR group). RESULTS: MRSA or VRE were identified in 29.9% of patients in the PCR group and in 9.6% in the standard group. Turn around time was 15 ± 9 hours in PCR group and 53 ± 23 hours in standard group. PCR group had a net cost of USD 245 per patient and standard group USD 530 per patient. DISCUSSION: PCR technique GeneXpert R for MRSA and VRE had a positive impact in the management of these patients and justifies its inclusion.

[Presence of Bordetella holmesii in an outbreak of pertussis in Chile]. / Presencia de Bordetella holmesii en brote epidémico de coqueluche en Chile.

The incidence of whooping cough in Chile ranges from 4.1 and 7.5 per hundred thousand inhabitants. B. pertussis detection is performed by Real Time PCR (Q-PCR) directed to the insertion sequence IS481. However, this sequence is also found in the genome of B. bronchiseptica and B. holmesii. The latter is also a respiratory pathogen whose clinical features are similar to B. pertussis. However, it is important to differentiate between these species because in immunosuppressed patients B. holmesii is more likely to cause bacteremia and is less susceptible to erythromycin. The goal of this work is to measure prospectively and retrospectively the presence of B. holmesii in samples reported positive for B. pertussis in the period 2010-2011. During this period, 1994 nasopharyngeal specimens entered the laboratory for Bordetella sp. PCR, of which 224 were positive. The analysis by Q-PCR directed to the recA gene of B. holmesii of all 224 positive samples determined a prevalence of B. holmesii of 0.6% (12/1994). Because of its more aggressive behavior in immunosupressed patients and its different resistance pattern, routine screening of B. pertussis and B. holmesii is currently performed for all samples in which Bordetella sp PCR is initially detected.

Different Safety Pattern of an Inactivated SARS-CoV-2 Vaccine (CoronaVac®) According to Age Group in a Pediatric Population from 3 to 17 Years Old, in an Open-Label Study in Chile.

During the COVID-19 pandemic, the importance of vaccinating children against SARS-CoV-2 was rapidly established. This study describes the safety of CoronaVac® in children and adolescents between 3- and 17-years-old in a multicenter study in Chile with two vaccine doses in a 4-week interval. For all participants, immediate adverse events (AEs), serious AEs (SAEs), and AEs of special interest (AESIs) were registered throughout the study. In the safety subgroup, AEs were recorded 28 days after each dose. COVID-19 surveillance was performed throughout the study. A total of 1139 individuals received the first and 1102 the second dose of CoronaVac®; 835 were in the safety subgroup. The first dose showed the highest number of AEs: up to 22.2% of participants reported any local and 17.1% systemic AE. AEs were more frequent in adolescents after the first dose, were transient, and mainly mild. Pain at the inoculation site was the most frequent AE for all ages. Fever was the most frequent systemic AE for 3-5 years old and headache in 6-17 years old. No SAEs or AESIs related to vaccination occurred. Most of the COVID-19 cases were mild and managed as outpatients. CoronaVac® was safe and well tolerated in children and adolescents, with different safety patterns according to age.

Safety and Non-Inferiority Evaluation of Two Immunization Schedules with an Inactivated SARS-CoV-2 Vaccine in Adults: A Randomized Clinical Trial.

Several vaccines have been developed to control the COVID-19 pandemic. CoronaVac®, an inactivated SARS-CoV-2 vaccine, has demonstrated safety and immunogenicity, preventing severe COVID-19 cases. We investigate the safety and non-inferiority of two immunization schedules of CoronaVac® in a non-inferiority trial in healthy adults. A total of 2302 healthy adults were enrolled at 8 centers in Chile and randomly assigned to two vaccination schedules, receiving two doses with either 14 or 28 days between each. The primary safety and efficacy endpoints were solicited adverse events (AEs) within 7 days of each dose, and comparing the number of cases of SARS-CoV-2 infection 14 days after the second dose between the schedules, respectively. The most frequent local AE was pain at the injection site, which was less frequent in participants aged ≥60 years. Other local AEs were reported in less than 5% of participants. The most frequent systemic AEs were headache, fatigue, and myalgia. Most AEs were mild and transient. There were no significant differences for local and systemic AEs between schedules. A total of 58 COVID-19 cases were confirmed, and all but 2 of them were mild. No differences were observed in the proportion of COVID-19 cases between schedules. CoronaVac® is safe, especially in ≥60-year-old participants. Both schedules protected against COVID-19 hospitalization.

Inactivated Vaccine-Induced SARS-CoV-2 Variant-Specific Immunity in Children.

Multiple vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been evaluated in clinical trials. However, trials addressing the immune response in the pediatric population are scarce. The inactivated vaccine CoronaVac has been shown to be safe and immunogenic in a phase 1/2 clinical trial in a pediatric cohort in China. Here, we report interim safety and immunogenicity results of a phase 3 clinical trial for CoronaVac in healthy children and adolescents in Chile. Participants 3 to 17 years old received two doses of CoronaVac in a 4-week interval until 31 December 2021. Local and systemic adverse reactions were registered for volunteers who received one or two doses of CoronaVac. Whole-blood samples were collected from a subgroup of 148 participants for humoral and cellular immunity analyses. The main adverse reaction reported after the first and second doses was pain at the injection site. Four weeks after the second dose, an increase in neutralizing antibody titer was observed in subjects relative to their baseline visit. Similar results were found for activation of specific CD4+ T cells. Neutralizing antibodies were identified against the Delta and Omicron variants. However, these titers were lower than those for the D614G strain. Importantly, comparable CD4+ T cell responses were detected against these variants of concern. Therefore, CoronaVac is safe and immunogenic in subjects 3 to 17 years old, inducing neutralizing antibody secretion and activating CD4+ T cells against SARS-CoV-2 and its variants. (This study has been registered at ClinicalTrials.gov under no. NCT04992260.) IMPORTANCE This work evaluated the immune response induced by two doses of CoronaVac separated by 4 weeks in healthy children and adolescents in Chile. To date, few studies have described the effects of CoronaVac in the pediatric population. Therefore, it is essential to generate knowledge regarding the protection of vaccines in this population. Along these lines, we reported the anti-S humoral response and cellular immune response to several SARS-CoV-2 proteins that have been published and recently studied. Here, we show that a vaccination schedule consisting of two doses separated by 4 weeks induces the secretion of neutralizing antibodies against SARS-CoV-2. Furthermore, CoronaVac induces the activation of CD4+ T cells upon stimulation with peptides from the proteome of SARS-CoV-2. These results indicate that, even though the neutralizing antibody response induced by vaccination decreases against the Delta and Omicron variants, the cellular response against these variants is comparable to the response against the ancestral strain D614G, even being significantly higher against Omicron.

Interim report: Safety and immunogenicity of an inactivated vaccine against SARS-CoV-2 in healthy chilean adults in a phase 3 clinical trial.

Background: The ongoing COVID-19 pandemic has had a significant impact worldwide, with an incommensurable social and economic burden. The rapid development of safe and protective vaccines against this disease is a global priority. CoronaVac is a vaccine prototype based on inactivated SARS-CoV-2, which has shown promising safety and immunogenicity profiles in pre-clinical studies and phase 1/2 trials in China. To this day, four phase 3 clinical trials are ongoing with CoronaVac in Brazil, Indonesia, Turkey, and Chile. This article reports the safety and immunogenicity results obtained in a subgroup of participants aged 18 years and older enrolled in the phase 3 Clinical Trial held in Chile. Methods: This is a multicenter phase 3 clinical trial. Healthcare workers aged 18 years and older were randomly assigned to receive two doses of CoronaVac or placebo separated by two weeks (0-14). We report preliminary safety results obtained for a subset of 434 participants, and antibody and cell-mediated immunity results obtained in a subset of participants assigned to the immunogenicity arm. The primary and secondary aims of the study include the evaluation of safety parameters and immunogenicity against SARS-CoV-2 after immunization, respectively. This trial is registered at clinicaltrials.gov ( NCT04651790 ). Findings: The recruitment of participants occurred between November 27 th , 2020, until January 9 th , 2021. 434 participants were enrolled, 397 were 18-59 years old, and 37 were ≥60 years old. Of these, 270 were immunized with CoronaVac, and the remaining 164 participants were inoculated with the corresponding placebo. The primary adverse reaction was pain at the injection site, with a higher incidence in the vaccine arm (55.6%) than in the placebo arm (40.0%). Moreover, the incidence of pain at the injection site in the 18-59 years old group was 58.4% as compared to 32.0% in the ≥60 years old group. The seroconversion rate for specific anti-S1-RBD IgG was 47.8% for the 18-59 years old group 14 days post immunization (p.i.) and 95.6% 28 and 42 days p.i. For the ≥60 years old group, the seroconversion rate was 18.1%, 100%, and 87.5% at 14, 28, and 42 days p.i., respectively. Importantly, we observed a 95.7% seroconversion rate in neutralizing antibodies for the 18-59 years old group 28 and 42 days p.i. The ≥60 years old group exhibited seroconversion rates of 90.0% and 100% at 28 and 42 days p.i. Interestingly, we did not observe a significant seroconversion rate of anti-N-SARS-CoV-2 IgG for the 18-59 years old group. For the participants ≥60 years old, a modest rate of seroconversion at 42 days p.i. was observed (37.5%). We observed a significant induction of a T cell response characterized by the secretion of IFN-γ upon stimulation with Mega Pools of peptides derived from SARS-CoV-2 proteins. No significant differences between the two age groups were observed for cell-mediated immunity. Interpretation: Immunization with CoronaVac in a 0-14 schedule in adults of 18 years and older in the Chilean population is safe and induces specific IgG production against the S1-RBD with neutralizing capacity, as well as the activation of T cells secreting IFN-γ, upon recognition of SARS-CoV-2 antigens. Funding: Ministry of Health of the Chilean Government; Confederation of Production and Commerce, Chile; Consortium of Universities for Vaccines and Therapies against COVID-19, Chile; Millennium Institute on Immunology and Immunotherapy.

Perfil de pacientes adultos hospitalizados por COVID-19 antes y después de la introducción de las vacunas contra SARS-CoV-2 / Profile of adult patients hospitalized with COVID-19 before and after the introduction of vaccines against SARS-CoV-2

INTRODUCCIÓN: La introducción progresiva de vacunas contra SARS-CoV-2 a partir de 2021, priorizando grupos de mayor edad, podría implicar un cambio en el perfil de pacientes hospitalizados por COVID-19 en el tiempo. OBJETIVO: Comparar las características y evolución de pacientes adultos hospitalizados por COVID-19 en un período anterior en 2020 (PER1) y otro posterior al inicio de la vacunación masiva contra SARS-CoV-2 (PER2). PACIENTES Y MÉTODOS: Se registró edad, género, comorbilidades, complicaciones y evolución de los pacientes hospitalizados por COVID-19 en una clínica privada, en Santiago, Chile. Se calculó el puntaje de gravedad y riesgo nutricional. RESULTADOS: En PER2, los pacientes fueron de menor edad, pero con comorbilidades similares al PER1, excepto por mayor malnutrición por exceso. Los pacientes del PER2 no vacunados requirieron más ventilación mecánica (38,9 vs. 14,3%, p = 0,03) y evolucionaron más gravemente (puntaje 6) que aquellos adecuadamente inmunizados (puntaje 5, p = 0,048). Las variables que más predijeron mortalidad fueron edad > 60 años (OR 28.995) y presencia de riesgo nutricional (OR 5.246). DISCUSIÓN: El cambio en el perfil y evolución de los pacientes hospitalizados con COVID-19 está asociado con la secuencia de priorización de vacunas contra SARS-CoV-2, cuyo efecto redujo las hospitalizaciones y gravedad de COVID-19 en adultos mayores.

BACKGROUND: During the COVID-19 pandemic, the early prioritization of SARS-CoV-2 vaccines for older adults may have affected the characteristics of hospitalized COVID-19 patients over time. AIM: To compare the clinical characteristics and outcomes of adult patients admitted for COVID-19 before (PER1) and after (PER2) the initiation of mass vaccination for SARS-CoV-2. METHODS: Data on age, gender, comorbidities, complications, and outcomes of adult patients hospitalized for COVID-19 in a private clinic of Santiago, Chile, were collected. Scores for COVID-19 severity and nutritional risk were calculated. RESULTS: In PER2, patients were younger but had similar comorbidities, except for a higher prevalence of overweight and obesity compared to PER1. Unvaccinated COVID-19 patients in PER2 required more invasive ventilatory support (38.9% vs. 14.3%, p = 0.03) and had a higher severity score (six) than vaccinated patients (five, p = 0.048). The variables that best predicted mortality were age > 60 years (OR 28,995) and the presence of nutritional risk (OR 5,246). DISCUSSION: Changes in the profile and outcomes of hospitalized patients during the COVID-19 pandemic are associated with the prioritization of SARS-CoV-2 vaccines and their protective effect in reducing hospitalizations and disease severity in older adults.

[Adherence to immunization among children with special health care needs]. / Adherencia a las inmunizaciones en niños con necesidades de cuidado médico especial.

UNLABELLED: The proportion of children with special health care needs (CSHCN) due to chronic illness is increasing. They have a high risk of complications due to infectious diseases. OBJECTIVE: To describe adherence to the Expanded Program of Immunization (EPI) and administration of other expert recommended vaccines in CSHCN. PATIENTS AND METHODS: In a retrospective manner information on chronic disease, EPI vaccines administration, reasons for delays, prescription and administration of additionally recommended vaccines was registered in a cohort of hospitalized CSHCN. RESULTS: Seventy children were analyzed. Thirty (42.9%) had at least one delay in EPI immunization schedule; 40% due to previous hospitalizations, 26.7% due to minor morbidity and 20% due to other unjustified reasons. Forty-nine (70.0%) received prescriptions for additional vaccines, but only 25 actually received them. CONCLUSIONS: CSHCN showed low adherence to EPI and received few additionally recommended vaccines. Every contact with these patients, including hospitalization should be used to update immunizations.

[Statement of the Advisory Committee on Immunizations of Sociedad Chilena de Infectología about outbreaks of hepatitis A in Chile]. / Opinión del Comité Consultivo de Inmunizaciones de la Sociedad Chilena de Infectología en relación a los brotes de hepatitis A en Chile.

This document represents the position of the Chilean Infectious Diseases Society Advisory Committee on Immunization Practices regarding hepatitis A epidemiological situation in Chile. The recommendations are based on local epidemiological data, the hepatitis A virus infection characteristics and the global experience with the available vaccines. In relation to hepatitis A, Chile is no longer a highly endemic area but actually an intermediate one, currently concentrating cases in individuals over 15 years of age, with frequent outbreaks. In 2017 we have seen an important outbreak of genotype 1A in men who have sex with men (MSM). The current endemic, the presence of regular outbreaks, the frequency of natural disasters in Chile, together with the availability of safe, effective vaccines and local cost-effectiveness studies led us to propose measures for outbreak control for high risk groups protection and mid and long term, including a more definitive solution which is universal vaccination against this disease in small children.

[Statement from the Immunization Committee of the Chilean Infectious Diseases Society in reference to vaccine refusal and mandatory policy on vaccination]. / Declaración del Comité Consultivo de Inmunizaciones de Sociedad Chilena de Infectología en relación a los cuestionamientos de las vacunas y su obligatoriedad.

Although vaccines have had a tremendous impact in public health they are questioned by certain groups that consider them unnecessary or unsafe and argue in favor of the right to decide to be vaccinated or not. However vaccines must have special considerations because unlike other medical decisions, not vaccinating has consequences not only for the individual but also for other members of the community. Immunizing a high proportion of the population limits the circulation of an infectious agent attaining what is called herd immunity that protects the susceptible members of the group. For this reason many countries consider vaccination mandatory as a responsibility of every citizen. This committee agrees with this view but thinks other strategies should be implemented as well, such as special educational efforts for the public and parents addressing benefits and real risks of vaccinating. Also health care professionals should be trained in vaccines. The notification system for adverse events currently available should be improved and be more accessible. Persons truly affected by adverse events due to vaccination should receive on time responses and be offered psychological and financial support. Finally all stakeholders should make coordinated efforts to work together to deliver messages that answer concerns on vaccines and bring confidence back to the public.

[Strategies to protect the newborn and infants under 6 months of age against pertussis: Statement of the Advisory Committee for Immunizations of the Chilean Infectious Diseases Society]. / Estrategias para proteger al recién nacido y lactante menor de 6 meses de la coqueluche: Posición del Comité Consultivo de Inmunizaciones de la Sociedad Chilena de Infectología (CCI).

In recent years there have been Pertussis outbreaks not seen in the last 50 years affecting adults, adolescents and children and causing deaths in young unvaccinated infants. In Chile an outbreak of Pertussis started in year 2011, leaving 16 infants less than 3 months dead during this year, twice the number seen in a non epidemic year. These children were infected before receiving the programmatic vaccines indicated at 2, 4 and 6 months of age, usually from close contacts, especially their mothers. Pertussis control has not been possible for several reasons, such as limited immunity duration of available vaccines and their poor impact on nasopharyngeal carriage, situation that keeps the agent's circulation and transmission, condition often asymptomatic or unrecognized. Additionally, the use of acellular vaccines appears to be a determining factor because they induce an immune response with poor immune memory and consequently a short time duration. The acellular vaccines with reduced antigen content, available for adolescents and adults, has allowed the evaluation of various strategies but none has succeeded in reducing infant mortality. Recently a new strategy of vaccinating pregnant women against Pertussis in the second or third semester has shown remarkable results reducing up to 90% infant deaths due to Pertussis infection. This strategy prevents mother's infection avoiding child infection through respiratory droplets and also provides the child with antibodies from placental transmission. Improved pertussis vaccines are required, in the meantime the Committee considers that the pregnant immunization strategy, between the 27 and 36 weeks, with acellular pertussis vaccine should be included in our national vaccine program.

[Reasons to recommend vaccination against dengue in Easter Island: Immunization Advisory Committee of Sociedad Chilena de Infectología]. / Razones para recomendar la vacunación contra el dengue en Isla de Pascua: Opinión del Comité de Inmunizaciones de la Sociedad Chilena de Infectología.

Dengue was first diagnosed on Easter Island on year 2002 and thereafter recurrent outbreaks have occurred involving different serotypes of dengue virus. Its vector, Aedes aegypti has not been eliminated despite the small size of the island. Conditions at the local hospital preclude adequate management of severe and hemorrhagic cases due to the absence of a Critical Care Unit as well as no availability of platelets, or plasma units for transfusion. Besides, transfer, of severely affected patients to continental Chile is cumbersome, slow and expensive. In this scenario, it is advisable to implement selective vaccination of Easter Island habitants with an available quadrivalent attenuated dengue vaccine with the aim to reduce hemorrhagic and severe dengue cases. This strategy should not replace permanent efforts to control waste disposal sites, water sources, maintain vector surveillance and increase education of the population.

[Statement of the Advisory Immunization Committee of the Chilean Society of Infectious Diseases on the emergence of serotype 19A pneumococcal infection and the use of pneumococcal conjugated vaccine in Chilean children]. / Opinión del Comité Consultivo de Inmunizaciones Sociedad Chilena de Infectología: Vacuna neumocóccica conjugada en niños y la emergencia de serotipo 19A.

Inclusion of the 10-valent pneumococcal conjugated vaccine (PCV10) in the Chilean infant vaccination Program in 2011 was followed by a reduction of hospital admissions and pneumonia-related deaths in this age group. However, a progressive increase of serotype 19A pneumococcal isolates (not included in PCV10) has been observed. According to the analysis of pneumococcal strains performed by the national reference laboratory of the Institute of Public Health as part of a national surveillance on invasive pneumococcal infections, the relative proportion of serotype 19A isolates increased from <5% before 2010 to 12-23% in years 2014-2015. Serotype 19A represented 4-8% of the isolates in the pre-vaccine era among children less than 2 years, increasing to 25% during 2014. This increase has been documented in two-thirds of the national territory. Aimong children <5 years of age, 25% of 19A serotype isolates from non-meningeal infections were penicillin resistant wheras from meningeal infections near 100% were penicillin resistant. Genetic analysis indicates that 48% of these 19A strains belong to clonal complex 320, recognized for its pandemic potential and high antimicrobial resistance. Among children, most invasive infections secondary to serotype 19A have occurred in patients fully vaccinated with PCV10. These epidemiological changes indicate an increase in invasive pneumococcal infections by serotype 19A in Chile and the need to control this problem by changing the current PCV10 for the PCV13 vaccine containing serotype 19A.