Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in young children. We previously estimated that in 2015, 33·1 million episodes of RSV-associated acute lower respiratory infection occurred in children aged 0-60 months, resulting in a total of 118 200 deaths worldwide. Since then, several community surveillance studies have been done to obtain a more precise estimation of RSV associated community deaths. We aimed to update RSV-associated acute lower respiratory infection morbidity and mortality at global, regional, and national levels in children aged 0-60 months for 2019, with focus on overall mortality and narrower infant age groups that are targeted by RSV prophylactics in development. METHODS: In this systematic analysis, we expanded our global RSV disease burden dataset by obtaining new data from an updated search for papers published between Jan 1, 2017, and Dec 31, 2020, from MEDLINE, Embase, Global Health, CINAHL, Web of Science, LILACS, OpenGrey, CNKI, Wanfang, and ChongqingVIP. We also included unpublished data from RSV GEN collaborators. Eligible studies reported data for children aged 0-60 months with RSV as primary infection with acute lower respiratory infection in community settings, or acute lower respiratory infection necessitating hospital admission; reported data for at least 12 consecutive months, except for in-hospital case fatality ratio (CFR) or for where RSV seasonality is well-defined; and reported incidence rate, hospital admission rate, RSV positive proportion in acute lower respiratory infection hospital admission, or in-hospital CFR. Studies were excluded if case definition was not clearly defined or not consistently applied, RSV infection was not laboratory confirmed or based on serology alone, or if the report included fewer than 50 cases of acute lower respiratory infection. We applied a generalised linear mixed-effects model (GLMM) to estimate RSV-associated acute lower respiratory infection incidence, hospital admission, and in-hospital mortality both globally and regionally (by country development status and by World Bank Income Classification) in 2019. We estimated country-level RSV-associated acute lower respiratory infection incidence through a risk-factor based model. We developed new models (through GLMM) that incorporated the latest RSV community mortality data for estimating overall RSV mortality. This review was registered in PROSPERO (CRD42021252400). FINDINGS: In addition to 317 studies included in our previous review, we identified and included 113 new eligible studies and unpublished data from 51 studies, for a total of 481 studies. We estimated that globally in 2019, there were 33·0 million RSV-associated acute lower respiratory infection episodes (uncertainty range [UR] 25·4-44·6 million), 3·6 million RSV-associated acute lower respiratory infection hospital admissions (2·9-4·6 million), 26 300 RSV-associated acute lower respiratory infection in-hospital deaths (15 100-49 100), and 101 400 RSV-attributable overall deaths (84 500-125 200) in children aged 0-60 months. In infants aged 0-6 months, we estimated that there were 6·6 million RSV-associated acute lower respiratory infection episodes (4·6-9·7 million), 1·4 million RSV-associated acute lower respiratory infection hospital admissions (1·0-2·0 million), 13 300 RSV-associated acute lower respiratory infection in-hospital deaths (6800-28 100), and 45 700 RSV-attributable overall deaths (38 400-55 900). 2·0% of deaths in children aged 0-60 months (UR 1·6-2·4) and 3·6% of deaths in children aged 28 days to 6 months (3·0-4·4) were attributable to RSV. More than 95% of RSV-associated acute lower respiratory infection episodes and more than 97% of RSV-attributable deaths across all age bands were in low-income and middle-income countries (LMICs). INTERPRETATION: RSV contributes substantially to morbidity and mortality burden globally in children aged 0-60 months, especially during the first 6 months of life and in LMICs. We highlight the striking overall mortality burden of RSV disease worldwide, with one in every 50 deaths in children aged 0-60 months and one in every 28 deaths in children aged 28 days to 6 months attributable to RSV. For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community. RSV passive immunisation programmes targeting protection during the first 6 months of life could have a substantial effect on reducing RSV disease burden, although more data are needed to understand the implications of the potential age-shifts in peak RSV burden to older age when these are implemented. FUNDING: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).

First prenatal case of Noonan syndrome with SOS2 mutation: Implications of early diagnosis for genetic counseling.

RASopathies are a group of syndromes with partially overlapping clinical features caused by germline mutations of the RAS/MAPK signaling pathway genes. The most common disorder is Noonan syndrome (NS; MIM 163950). We report the first prenatal case of NS with SOS2 (NM_006939.4) mutation in a euploid fetus with a severe increase in nuchal translucency (NT > 12 mm). Trio-based custom next-generation sequencing detected a de novo heterozygous missense mutation in the SOS2 gene: c.800 T > A (p.Met267Lys). Owing to the marked variable expressivity of NS and the scarcity of SOS2 mutation-related NS cases reported in the literature, it is difficult to provide appropriate genetic counseling. Several issues such as the best management technique and optimal NT cutoff have been discussed. In addition, in general, the fine balance between the advantages of an early prenatal diagnosis and the challenge of determining if the detected gene variant is pathogenic and, primarily, the stress of the counselees when providing a genetic counseling with limited information on the prenatal phenotype have been discussed. A prenatal path comprising examinations and multidisciplinary counseling is essential to support couples in a shared decision-making process.

Global and regional burden of hospital admissions for severe acute lower respiratory infections in young children in 2010: a systematic analysis.

BACKGROUND: The annual number of hospital admissions and in-hospital deaths due to severe acute lower respiratory infections (ALRI) in young children worldwide is unknown. We aimed to estimate the incidence of admissions and deaths for such infections in children younger than 5 years in 2010. METHODS: We estimated the incidence of admissions for severe and very severe ALRI in children younger than 5 years, stratified by age and region, with data from a systematic review of studies published between Jan 1, 1990, and March 31, 2012, and from 28 unpublished population-based studies. We applied these incidence estimates to population estimates for 2010, to calculate the global and regional burden in children admitted with severe ALRI in that year. We estimated in-hospital mortality due to severe and very severe ALRI by combining incidence estimates with case fatality ratios from hospital-based studies. FINDINGS: We identified 89 eligible studies and estimated that in 2010, 11·9 million (95% CI 10·3-13·9 million) episodes of severe and 3·0 million (2·1-4·2 million) episodes of very severe ALRI resulted in hospital admissions in young children worldwide. Incidence was higher in boys than in girls, the sex disparity being greatest in South Asian studies. On the basis of data from 37 hospital studies reporting case fatality ratios for severe ALRI, we estimated that roughly 265,000 (95% CI 160,000-450,000) in-hospital deaths took place in young children, with 99% of these deaths in developing countries. Therefore, the data suggest that although 62% of children with severe ALRI are treated in hospitals, 81% of deaths happen outside hospitals. INTERPRETATION: Severe ALRI is a substantial burden on health services worldwide and a major cause of hospital referral and admission in young children. Improved hospital access and reduced inequities, such as those related to sex and rural status, could substantially decrease mortality related to such infection. Community-based management of severe disease could be an important complementary strategy to reduce pneumonia mortality and health inequities. FUNDING: WHO.

National survey for pediatricians in Argentina: Vaccination in daily practice, perception of knowledge and barriers. / Encuesta nacional para pediatras de Argentina: vacunación en la práctica diaria, percepción de conocimientos y barreras.

Introduction. The decline in vaccination coverage has been very significant in the past decade. Pediatricians play a key role in catching-up coverage and increasing confidence in vaccination. Objectives. To describe pediatricians' perceptions of vaccine knowledge and practices and to identify barriers to access. Methods. Observational, analytical study using an online survey. Variables related to professional profile, training and barriers to vaccination were included. Results. A total of 1696 pediatricians participated (response rate: 10.7%). Their mean age was 50.4 years; 78.7% were women; 78.2% had ≥ 10 years of experience; 78.4% provided outpatient care and 56.0%, in the private subsector; and 72.5% received training in the past 2 years. Respondents described themselves as "trained" in convey the following aspects to their patients: benefits of vaccines: 97.2%; campaign objectives: 87.7%; contraindications: 82.4%; adverse effects: 78.9%; catch- up vaccination: 71.2%; reporting of events supposedly attributable to vaccination or immunization: 59.5%. The proportion was statistically higher in all aspects, among pediatricians with ≥ 10 years of experience and those who received training recently (p ≤ 0.01). The barriers identified in access to vaccination were false contraindications (62.3%), temporary vaccine shortage (46.4%), cultural reasons (41.4%), and restricted vaccination center hours (40.6%). Conclusions. The perception of the level of training varied depending on the vaccination-related aspect. Pediatricians with more years of professional experience and those who received recent updates perceived themselves as more trained. Multiple barriers associated with access to vaccination were identified.

Introducción. El descenso de las coberturas de vacunación fue muy significativo en la última década. Los pediatras son una pieza fundamental para recuperar coberturas y aumentar la confianza en la vacunación. Objetivos. Describir la percepción de los pediatras acerca del conocimiento y prácticas sobre vacunas, e identificar barreras en el acceso. Métodos. Estudio analítico observacional, mediante encuesta en línea. Se incluyeron variables del perfil del profesional, capacitación y barreras en inmunizaciones. Resultados. Participaron 1696 pediatras (tasa de respuesta: 10,7 %), media de 50,4 años. El 78,7 % fueron mujeres. El 78,2 % contaba con ≥10 años de ejercicio profesional. El 78,4 % realizaba atención ambulatoria y el 56,0 % en el subsector privado. El 72,5 % realizó una capacitación en los últimos 2 años. Se manifestaron "capacitados" para transmitir a sus pacientes los beneficios de las vacunas: 97,2 %; objetivos de campañas: 87,7 %; contraindicaciones: 82,4 %; efectos adversos: 78,9 %; recupero de esquemas: 71,2 %; notificación de ESAVI: 59,5 %. La proporción fue estadísticamente superior, en todos los aspectos, en pediatras con ≥10 años de ejercicio y en aquellos con capacitación reciente (p ≤ 0,01). Barreras identificadas en el acceso a la vacunación: falsas contraindicaciones (62,3 %); falta temporaria de vacunas (46,4 %); motivos culturales (41,4 %); horario restringido del vacunatorio (40,6 %). Conclusiones. La percepción del grado de capacitación fue variable según el aspecto de la vacunación. Aquellos con mayor tiempo de ejercicio profesional y con actualización reciente se manifestaron con mayor grado de capacidad. Se identificaron múltiples barreras frecuentes asociadas al acceso en la vacunación.

Hepatitis A virus infection.

Hepatitis A is a vaccine-preventable infection caused by the hepatitis A virus (HAV). Over 150 million new infections of hepatitis A occur annually. HAV causes an acute inflammatory reaction in the liver that usually resolves spontaneously without chronic sequelae. However, up to 20% of patients experience a prolonged or relapsed course and <1% experience acute liver failure. Host factors, such as immunological status, age, pregnancy and underlying hepatic diseases, can affect the severity of disease. Anti-HAV IgG antibodies produced in response to HAV infection persist for life and protect against re-infection; vaccine-induced antibodies against hepatitis A confer long-term protection. The WHO recommends vaccination for individuals at higher risk of infection and/or severe disease in countries with very low and low hepatitis A virus endemicity, and universal childhood vaccination in intermediate endemicity countries. To date, >25 countries worldwide have implemented such programmes, resulting in a reduction in the incidence of HAV infection. Improving hygiene and sanitation, rapid identification of outbreaks and fast and accurate intervention in outbreak control are essential to reducing HAV transmission.

Evolutionary dynamics of respiratory syncytial virus in Buenos Aires: Viral diversity, migration, and subgroup replacement.

Globally, the human respiratory syncytial virus (RSV) is one of the major causes of lower respiratory tract infections (LRTIs) in children. The scarcity of complete genome data limits our understanding of RSV spatiotemporal distribution, evolution, and viral variant emergence. Nasopharyngeal samples collected from hospitalized pediatric patients from Buenos Aires tested positive for RSV LRTI during four consecutive outbreaks (2014-2017) were randomly subsampled for RSV complete genome sequencing. Phylodynamic studies and viral population characterization of genomic variability, diversity, and migration of viruses to and from Argentina during the study period were performed. Our sequencing effort resulted in one of the largest collections of RSV genomes from a given location (141 RSV-A and 135 RSV-B) published so far. RSV-B was dominant during the 2014-2016 outbreaks (60 per cent of cases) but was abruptly replaced by RSV-A in 2017, with RSV-A accounting for 90 per cent of sequenced samples. A significant decrease in RSV genomic diversity-represented by both a reduction in genetic lineages detected and the predominance of viral variants defined by signature amino acids-was observed in Buenos Aires in 2016, the year prior to the RSV subgroup predominance replacement. Multiple introductions to Buenos Aires were detected, some with persistent detection over seasons, and also, RSV was observed to migrate from Buenos Aires to other countries. Our results suggest that the decrease in viral diversity may have allowed the dramatic predominance switch from RSV-B to RSV-A in 2017. The immune pressure generated against circulating viruses with limited diversity during a given outbreak may have created a fertile ground for an antigenically divergent RSV variant to be introduced and successfully spread in the subsequent outbreak. Overall, our RSV genomic analysis of intra- and inter-outbreak diversity provides an opportunity to better understand the epochal evolutionary dynamics of RSV.

Role of Noroviruses in Sporadic Acute Gastroenteritis Cases from Children Attending a Large Referral Children's Hospital in Buenos Aires City, Argentina.

BACKGROUND: Noroviruses (NVs) are recognized as the leading cause of sporadic and epidemic acute gastroenteritis worldwide, in all age groups. Although there is increasing knowledge that NVs are responsible for many acute gastroenteritis outbreaks in Argentina, studies to estimate prevalence in sporadic cases are scarce. METHODS: A descriptive, observational and cross-sectional study was conducted with children under 5 years with acute gastroenteritis attending the outpatient department at the "Ricardo Gutiérrez" Children's Hospital (RGCH) in Buenos Aires City between June 2017 and June 2021. Sociodemographic, clinical and epidemiologic data were recorded. Stool samples were tested and genotyped for norovirus. Association between norovirus detection and demographic and clinical variables was assessed. RESULTS: A total of 350 children with acute diarrhea were included, of which stool samples were collected for 332 (94.9%). Norovirus was detected in 81 cases (24.4%). Vomiting and moderate/severe diarrhea were more frequent in norovirus-positive than norovirus-negative children. However, the presence of watery diarrhea and a history of rotavirus vaccination were significantly associated with norovirus etiology. GII and GII.4 were the most frequently detected genogroup and genotype, respectively. CONCLUSIONS: NVs were detected with high frequency, mostly in children between 6 months and 2 years old, reinforcing the hypothesis of a newly updated scenario of norovirus predominance over rotavirus. Watery diarrhea, complete vaccination against rotavirus and vomiting are 3 key parameters that should raise suspicion of possible norovirus gastroenteritis. Continuous and active norovirus surveillance in this age group is important because children represent a priority group for norovirus vaccine design and development.

Vaccination status in patients at risk for invasive disease with encapsulated bacteria at a children's hospital in the City of Buenos Aires. / Estado de vacunación en pacientes con riesgo de enfermedades invasoras por bacterias capsuladas en un hospital pediátrico de Buenos Aires.

Introduction. The Ministry of Health has established specific vaccines for people at high risk for invasive infections with encapsulated bacteria (EB). There is currently no information about compliance with the vaccination schedule. Our objective was to assess EB vaccination status in subjects ≤ 18 years with risk factors. Population and methods. Observational, analytical study with a survey to parents of subjects aged ≤ 18 years with HIV, asplenia and/or complement deficiency attending a vaccination center at a children's hospital between October 2020 and September 2021. Sociodemographic and clinical data were collected. Their vaccination status for the EB pneumococcus, meningococcus, and Haemophilus influenzae type b (Hib), their regular vaccination and flu vaccination schedules were assessed. The vaccine hesitancy scale (VHS) was administered: range 10-50. The association between the study variables and EB vaccination was analyzed using logistic regression (OR, 95% CI). The REDCap® database and the STATA ® v.14 software were used. Results. A total of 104 subjects participated; mean age: 9.9 years (SD: 4.4). Asplenia: 91.3%, HIV: 7.6%, and complement deficiency: 0.9%. Socioeconomic level: relative poverty: 38.4%, followed by middle class: 37.5%. Complete vaccination status: meningococcal vaccine 45%, pneumococcal vaccine: 42%, Hib: 97%. The regular vaccination and flu vaccination schedules were up-to-date in 77.9% and 61.5% of cases, respectively. Mean VHS score: 41.9 (SD: 3.2). No significant associations were observed between variables and EB vaccination status. Conclusions. A high percentage of subjects had not completed neither their EB vaccination nor their regular or their flu vaccination schedules. Caregivers' confidence in vaccines was high.

Introducción. El Ministerio de Salud contempla vacunas específicas para personas con riesgo elevado de infecciones invasoras por bacterias capsuladas (BC). En la actualidad se desconoce el cumplimiento del programa. El objetivo fue evaluar el estado de vacunación para BC en ≤ 18 años con factores de riesgo. Población y métodos. Estudio observacional, analítico, mediante encuesta a padres de ≤ 18 años con VIH, asplenia y/o déficit de complemento que concurrieron al vacunatorio de un hospital pediátrico de octubre de 2020 a septiembre de 2021. Se recabaron datos sociodemográficos y clínicos. Se evaluó el estado de vacunación para BC: neumococo, meningococo y Haemophilus influenzae b (Hib), calendario regular y antigripal. Se administró la escala de reticencia a la vacunación (ERV): rango 10-50. Se analizó la asociación entre las variables estudiadas y la vacunación para BC mediante regresión logística (OR, IC95%). Se utilizó la base datos REDCap® y STATA vs14 ® . Resultados. Participaron 104 sujetos, media 9,9 años (DE 4,4). Asplenia: 91,3 %, VIH: 7,6 % y déficit de complemento: 0,9 %. Nivel socioeconómico: pobreza relativa: 38,4 %, seguido por clase media: 37,5 %. Estado de vacunación completa para meningococo: 45 %, neumococo: 42 %, Hib: 97 %. El 77,9 % tenía al día el calendario regular y el 61,5 %, el antigripal. Media ERV: 41,9 (DE 3,2). No se encontraron asociaciones significativas entre las variables y el estado de vacunación para BC. Conclusiones. Un elevado porcentaje no tenía vacunación completa para BC, tampoco el calendario regular y antigripal. La confianza en la vacunación de los cuidadores fue elevada.

Vaccination against pertussis in Latin American preterm and low-birth weight infants: experts opinion position for a neglected childhood age group.

BACKGROUND: Pertussis remains as one of the oldest leading vaccine-preventable diseases of childhood, despite many decades of primary vaccine doses' and boosters' implementation. Although the epidemiology is well understood in infants and children, premature babies and low-birth weight infants remain a special group where the disease incidence is unknown, severity of the disease is considerable, and specific vaccination recommendations are scarce. RESEARCH DESIGN AND METHODS: A retrospective review of the available evidence of pertussis vaccination in premature and low birth weight infants was analyzed from January 2000 to December 2022 in six selected countries: Argentina, Mexico, Colombia, Panamá, Costa Rica, and Chile. RESULTS: Chile had reports of adverse effects associated with vaccination of premature infants with the pentavalent vaccine, and their rationale to switching to the hexavalent vaccine. Colombia had reports of the justification for the use of hexavalent vaccine in prematures in the Neonatal Units and Kangaroo Mother Programs throughout the country. Mexico had selected publications of the vaccination status in prematures and low-birth weight infants. CONCLUSION: Despite its importance, increased morbidity, and highest risk of complications in premature babies, there is a paucity of information of vaccine recommendations and coverage rates among selected Latin American infants.

Infant vaccination against pertussis in Argentina: Parent-reported outcomes on reactogenicity, impact on daily routine and satisfaction after pentavalent whole-cell or hexavalent acellular pertussis vaccines.

Introduction: In Argentina, a pentavalent whole-cell pertussis vaccine (wP) is used in the National Immunization Program, however hexavalent acellular pertussis (aP) vaccines are available in the private market. Objective: To describe parent or guardians perceptions on reactogenicity, daily routine and satisfaction after a first or third dose of a wP-pentavalent plus IPV (wP-group) or the fully-liquid aP-hexavalent vaccine (aP-group) in infants. Material and methods: This was a prospective observational and analytical study. Parents or guardians of infants born at term attending a public or private vaccination center in Buenos Aires City were invited to participate. All parents or guardians had completed 12-year schooling and were asked to fill out an online 7-day post vaccination questionnaire. The questionnaire was validated as the first phase of the study. Descriptive analysis of study variables was carried out, REDCap was used for the online survey, and STATA 14 for data analysis. Results: 1071 parents or guardians answered the questionnaire (response rate 82%), 530 for wP-group and 541 for aP-group.Local and systemic adverse reactions, in groups wP and aP respectively, were: pain 83%, 28%; swelling 63%, 16%; redness 52%, 22%; irritability 72%, 52%; fever 37%, 8%; loss of appetite 36%, 19%; drowsiness 38%, 27%; and vomiting 15%, 11%.Impact on daily life: social activities 36%, 20%; routine 48%, 24%; mood 39%, 23%; vitality 47%, 24%; sleep 50%, 30%; and appetite 22%, 7%.Parents were satisfied with the vaccination process in 96% and 98% for wP-group and aP-group respectively. Parents reported willingness to bring infant for future vaccine doses in 97% and 99% for wP-group and aP-group respectively. Conclusions: Reported reactogenicity and impact on family daily routine was higher in infants receiving wP-pentavalent than aP-hexavalent vaccines. Parents in both groups conveyed vaccine acceptance and positive intentions for future immunizations.

Epidemiology of Meningococcal Disease in Four South American Countries and Rationale of Vaccination in Adolescents from the Region: Position Paper of the Latin American Society of Pediatric Infectious Diseases (SLIPE).

Surveillance of meningococcal disease (MD) is crucial after the implementation of vaccination strategies to monitor their impact on disease burden. Adolescent vaccination could provide direct and indirect protection. Argentina, Brazil, and Chile have introduced meningococcal conjugate vaccines (MCV) into their National Immunization Programs (NIP), while Uruguay has not. Here, we analyze the epidemiology of MD and vaccination experience from these four South American countries to identify needs and plans to improve the current vaccination programs. METHODOLOGY: Descriptive study of MD incidence rates, serogroup distribution, case fatality rates (CFR), and MCV uptakes during the period 2010-2021 in Argentina, Brazil, Chile, and Uruguay. Data were extracted from national surveillance programs, reference laboratories, NIPs, and Pubmed. RESULTS: MD overall incidence from 2010 to 2021 have a decreasing trend in Argentina (0.37 [IQR = 0.20-0.61]), Brazil (0.59 [IQR = 0.54-1.22]), and Chile (0.45 [IQR = 0.40-0.77]), while a significant increase in Uruguay (0.47 [IQR = 0.33-0.69]) was found from 2016 to 2019. During the COVID-19 pandemic, all countries sharply reduced their MD incidence. The highest incidence rates were observed among infants, followed by children 1-4 years of age. No second peak was evident in adolescents. A reduction in serogroup C, W, and Y cases has occurred in Argentina, Brazil, and Chile after introduction of MCV, serogroup B becoming predominant in all four countries. Median CFR was 9.0%, 21%, 19.9%, and 17.9% in Argentina, Brazil, Chile, and Uruguay, respectively. Median uptake of MCV for Argentina and Brazil were 66.6% and 91.0% for priming in infants; 54.7% and 84.5% for booster in toddlers; and 47.5% and 53% for adolescents; while for Chile, 95.6% for toddlers. CONCLUSIONS: Experience after the implementation of MCV programs in South America was successful, reducing the burden of MD due to the vaccine serogroups. High vaccine uptake and the inclusion of adolescents will be crucial in the post-pandemic period to maintain the protection of the population. The increase in the proportion of serogroup B cases emphasizes the importance of continuous surveillance to guide future vaccination strategies.

Risks of low vaccination coverage and strategies to prevent the resurgence of vaccine-preventable diseases in infants in the COVID-19 pandemic scenario: recommendations for Latin America and the Caribbean by the group of experts on infant immunization for Latin America.

INTRODUCTION: The WHO 2030 Immunization Agenda (IA-2030) harmonizes immunization activity plans at community, national, regional and global levels. Additionally, medical societies play an important role. The Latin American Group of Experts on Infant Immunization, established in 2018, advises on the harmonization, update, and optimization of infant vaccination programs in Latin America and the Caribbean (LAC). In September 2021, 41 such experts from 13 LAC countries met to develop recommendations for increasing regional vaccination coverage to avoid the reemergence of vaccine-preventable diseases and/or the occurrence of outbreaks. AREAS COVERED: The following items were evaluated: (i) immunization challenges before and during the COVID-19 pandemic; (ii) the status of current immunization programs, particularly infant pertussis and polio vaccination; (iii) possible solutions for overcoming vaccination challenges and achieving regional vaccination coverage targets. EXPERT OPINION/COMMENTARY: Medical societies provide valuable recommendations to guide and update vaccination schedules. In the LAC region, possible strategies to achieve target vaccination rates include the use of combination vaccines, strengthening surveillance systems, improving school attendance, advancing vaccine education and confidence, striving for vaccination equity, widening operational capacity, creating strategic alliances, and strengthening the role of medical groups. It is hoped that these recommendations will be implemented in the LAC region.

Are the first 1,000 days of life a neglected vital period to prevent the impact on maternal and infant morbimortality of infectious diseases in Latin America? Proceedings of a workshop of experts from the Latin American Pediatric Infectious Diseases Society, SLIPE.

While the first 1,000 days of life are a critical period in child's development, limited information on the main determinants affecting this period in the Latin America and the Caribbean (LAC) region is available. Therefore, the Latin American Pediatric Infectious Diseases Society (SLIPE) held an ad hoc workshop in May 2022 with an expert panel designed to analyze the main factors impacting the development of childhood in the region during this period and the main causes of maternal infant morbimortality. The aim was to identify priorities, generate recommendations, and advise practical actions to improve this situation. Considerations were made about the challenges involved in bridging the gap that separates the region from more developed countries regarding an optimal early childhood and maternal care. Extensive discussion was conducted to reach consensus recommendations on general strategies intended to reduce maternal and infant mortality associated with infections and immune-preventable diseases during the first 1,000 days of life in LAC.

Comparison of Epidemiologic and Clinical COVID-19 Profiles in Children in Argentina, During Circulation of Original and Variant (Alpha, Gamma and Lambda) Strains.

BACKGROUND: Information on the impact of the different variants in children in Latin America is scarce. The objective of this study was to describe epidemiologic and clinical features of COVID-19 infection in children under 18 years of age in Argentina, comparing the periods before and after the circulation of new variants. METHODS: Observational, cross-sectional, multicentric, analytical study. All patients under 18 years of age with confirmed SARS-CoV-2 infection admitted at 22 healthcare centers were included. Two study periods were established: Period 1 (EW10-2020 to EW12-2021) for the Wuhan strain; Period 2 (EW13 to EW35 2021) for Alpha, Gamma, Delta and Lambda variants. FINDINGS: A total of 6330 confirmed cases were included. Period 1: 3575 (56.5%), period 2: 2755 (43.5%). During period 2, a lower number of asymptomatic cases was observed, while general, respiratory and neurologic signs and symptoms increased in all age groups. Oxygen therapy requirement was higher during the first period (36.7% vs 19.1%; P < 0.001). No significant differences were observed in the rates of severe or critical cases (6.3% vs 5,4%; P = 0.102), intensive care admission (2.1% vs 2%; P < 0.656) or case fatality (0.3% vs 0.5 %; P < 0.229). MIS-C cases occurred more frequently during the first period (1.9% vs 1.1%; P = 0.009). INTERPRETATION: The clinical spectrum of COVID-19 in Argentina has evolved. With the emergence of new variants, although the number of asymptomatic cases declined, numbers of severe and critical cases, as well as case fatality rates in children, remained unchanged.

Incidence of Respiratory Syncytial Virus-Associated Lower Respiratory Tract Illness in Infants in Low- and Middle-Income Regions During the Coronavirus Disease 2019 Pandemic.

Background: Incidence data of respiratory syncytial virus-associated lower respiratory tract illness (RSV-LRTI) are sparse in low- and middle-income countries (LMICs). We estimated RSV-LRTI incidence rates (IRs) in infants in LMICs using World Health Organization case definitions. Methods: This prospective cohort study, conducted in 10 LMICs from May 2019 to October 2021 (largely overlapping with the coronavirus disease 2019 [COVID-19] pandemic), followed infants born to women with low-risk pregnancies for 1 year from birth using active and passive surveillance to detect potential LRTIs, and quantitative reverse-transcription polymerase chain reaction on nasal swabs to detect RSV. Results: Among 2094 infants, 32 (1.5%) experienced an RSV-LRTI (8 during their first 6 months of life, 24 thereafter). Seventeen (0.8%) infants had severe RSV-LRTI and 168 (8.0%) had all-cause LRTI. IRs (95% confidence intervals [CIs]) of first RSV-LRTI episode were 1.0 (.3-2.3), 0.8 (.3-1.5), and 1.6 (1.1-2.2) per 100 person-years for infants aged 0-2, 0-5, and 0-11 months, respectively. IRs (95% CIs) of the first all-cause LRTI episode were 10.7 (8.1-14.0), 11.7 (9.6-14.0), and 8.7 (7.5-10.2) per 100 person-years, respectively. IRs varied by country (RSV-LRTI: 0.0-8.3, all-cause LRTI: 0.0-49.6 per 100 person-years for 0- to 11-month-olds). Conclusions: RSV-LRTI IRs in infants in this study were relatively low, likely due to reduced viral circulation caused by COVID-19-related nonpharmaceutical interventions. Clinical Trials Registration: NCT03614676.

Outpatient management of childhood acute diarrhea: survey among pediatricians from a children's hospital in the Autonomous City of Buenos Aires. / Manejo ambulatorio de la diarrea aguda infantil: encuesta a pediatras de un hospital pediátrico de la Ciudad de Buenos Aires.

INTRODUCTION: The management of acute diarrhea is based on preventing dehydration and reducing disease duration and severity. , Ángela Gentilea INTRODUCTION The study objective was to establish the patterns for the outpatient management of acute diarrhea in children younger than 5 years. METHODS: Observational, analytical study using a self-administered survey among pediatricians from a children's hospital in the Autonomous City of Buenos Aires.Age, sex, place of work, bibliographic sources, indication of drug and non-drug therapies, and preventive and hygiene measures were recorded. The association between drug prescription and the characteristics of surveyed pediatricians was assessed. RESULTS: In total, 182/216 pediatricians completed the survey. Their mean age was 42.4 ± 10.24 years; 78.6% were females; 59.2% worked in the public sector; 22.4% worked in the emergency department; and 91.2% consulted guidelines and/or consensuses. Also, 92.9% prescribed oral rehydration solutions; 46.2%, antiemetics; 43.4%, antacids and/or gastric protectors; 35.7%, probiotics; and 30.7%, zinc. Early food reintroduction was indicated by 91.7%; breastfeeding, by 96.7%; and preventive and hygiene measures, by 96-100%. The multivariate analysis showed an association between age > 40 years and prescribing antacids/ gastric protectors (odds ratio [OR]: 2.6; 1.22-5.61), probiotics (OR: 3.03; 1.34-6.83), and zinc (OR: 0.39; 0.17-0.87); between working in the private sector and prescribing probiotics (OR: 3.05; 1.565.94); and between working in the emergency department and prescribing antacids/gastric protectors (OR: 2.60; 1.22-5.54). CONCLUSIONS: Treatment was mainly based on hydration, early food reintroduction, and breastfeeding. Age and work sector affected the prescription pattern.

Introducción. El tratamiento de la diarrea aguda se basa en prevenir la deshidratación, reducir la duración y gravedad de la enfermedad. El objetivo fue conocer los patrones de tratamiento ambulatorio de la diarrea aguda en<5 años. , Anabella C. Pacchiottia,b , Cómo citar: Castelllano VE, Giglio ND, Pacchiotti AC, Gentile Á. Manejo ambulatorio de la diarrea aguda infantil: encuesta a pediatras de un hospital pediátrico de la Ciudad de Buenos Aires. Arch Argent Pediatr 2022;120(1):46-53. a. División Promoción y Protección de la Salud, Área Epidemiología. b. Departamento de Urgencia. Hospital de Niños Dr. Ricardo Gutiérrez, Ciudad Autónoma de Buenos Aires, Argentina. Correspondencia: Vanesa E. Castellano: vane0108@hotmail.com Financiamiento: Este estudio recibió colaboración irrestricta del laboratorio Sanofi Aventis, utilizada para el material de las encuestas, equipamiento informático y una beca educacional para la Dra. Anabella Pacchiotti. Conflicto de intereses: V. Castellano, N. Giglio y Á. Gentile han participado como disertantes de conferencias auspiciadas por el laboratorio Sanofi Aventis en congresos y jornadas. Recibido: 11-5-2021 Aceptado: 15-9-2021 Métodos. Estudio observacional, analítico, mediante encuestas autoadministradas a pediatras de un hospital de niños de la Ciudad Autónoma de Buenos Aires. Se indagó: edad, sexo, lugar de trabajo, fuentes bibliográficas, indicación de tratamientos farmacológicos, no farmacológicos y medidas de prevención e higiene. Se evaluó la asociación entre prescripciones farmacológicas y características de los encuestados. Resultados. Respondieron 182/216 pediatras; la edad media fue 42,4 ± 10,24 años (el 78,6 %, mujeres); el 59,2 %, del sector público; el 22,4 %, de servicios de guardia. El 91,2 % consultaba guías/consensos. El 92,9 % prescribió fórmulas de rehidratación oral; el 46,2 %, antieméticos; el 43,4 %, antiácidos y/o protectores gástricos; el 35,7 %, probióticos, y el 30,7 %, cinc. El 91,7 % indicó realimentación precoz; el 96,7 %, lactancia materna y el 96-100 %, medidas de prevención e higiene. En el análisis multivariado, tener >40 años se asoció con prescribir antiácidos/protectores gástricos (odds ratio [OR] 2,6; 1,22-5,61), probióticos (OR 3,03; 1,34-6,83) y cinc (OR 0,39; 0,17-0,87); trabajar en el sector privado con prescribir probióticos (OR 3,05; 1,56-5,94) y en servicios de guardia, con prescribir antiácidos/ protectores gástricos (OR 2,60; 1,22-5,54). Conclusiones. El tratamiento se basó principalmente en hidratación, alimentación precoz y lactancia. La edad y el lugar de desempeño de los pediatras modifican el patrón de prescripción.

COVID-19 in Children: Correlation Between Epidemiologic, Clinical Characteristics, and RT-qPCR Cycle Threshold Values.

BACKGROUND: Initially, the impact of SARS-CoV-2 infection on children was unknown. Standard COVID-19 diagnosis is confirmed using real-time qPCR. Cycle threshold (Ct) values of RT-qPCR are inversely proportional to viral load and the test indirectly quantifies viral RNA copy numbers. The objective of this study was to determine the correlation between epidemiology, clinical characteristics, severity of confirmed COVID-19 cases, and Ct values. METHODS: An observational, analytical, cross-sectional study. All children with COVID-19 under 18 years old admitted to the Ricardo Gutiérrez Children's Hospital between March 1, 2020, and February 28, 2021, were included. SARS-CoV-2 infection was confirmed using RT-qPCR. RESULTS: Median age of patients was 7 years. Ct values were estimated in 419 cases, median Ct value was 23.5 [interquartile range (IQR): 18.9-30.9]. Levels were significantly lower in symptomatic than asymptomatic patients (Ct: 22.1; IQR: 18.4-22.1), in children <2 years of age (Ct: 20.6; IQR: 17.3-27.3) and when sample collection was <4 days after symptom onset (Ct: 21.1; IQR: 18.1-27.5). In children >2 years of age, Ct values were significantly lower in symptomatic (Ct: 22.6; IQR: 18.7-29.3) than asymptomatic (Ct: 31.2; IQR: 24.5-33.3) patients. CONCLUSIONS: Children younger than 2 years with COVID-19 have lower values of Ct-as a proxy for higher viral load-than older children. Symptomatic children over 2 years of age had lower Ct values compared with asymptomatic children.

Impact of varicella vaccination in Argentina: Seroprevalence in children and adults in a pediatric hospital.

BACKGROUND: Varicella is the primary infection caused by varicella-zoster virus (VZV). In Argentina, the varicella vaccine was introduced in the National Immunization Programme in 2015 as a single dose scheduled at 15 months of age. OBJECTIVES: To estimate VZV seroprevalence in a healthy hospital based population before and after vaccine introduction to the NIP. MATERIAL Y METHODS: Cross-sectional, observational, analytic study. Healthy subjects 1-40 years of age were included between June and December 2019 and tested for VZV-antibodies. Results were compared to data from a similar prevaccination study. RESULTS: Out of 599 samples, 11 indeterminate results were excluded, 424 were positive; overall seroprevalence rate was 72.1% (95 %CI = 68,3-75,8%). No differences were observed between pre and post vaccination studies for overall prevalence or between age groups, except for vaccinated children aged 11-15 (p = 0,005). Rates increased in both periods in subjects aged 6 years or older. Primary vaccine failures were 21%; in subjects <5 years 83% seropositive cases had been vaccinated, in >5 year-olds >90% seropositive cases were associated with a history of infection (OR: 10,4; IC95%: 6,4-16,8; p < 0,001) or household contact (OR:4,8; IC95%: 3,1-7,6; p < 0,001). Vaccination protected against disease (OR: 0.25; 95 %CI: 0.09-0.68; p = 0.004). CONCLUSION: seroprevalence was high in all age groups except in unvaccinated 12 to 15-month infants. Seropositivity was due to vaccination in 15 months to 5 year-old children and to infection in older children.

Impact of COVID-19 on the circulation of respiratory viruses in a children's hospital: an expected absence. / Impacto del COVID-19 en la circulación de virus respiratorios en un hospital pediátrico: una ausencia esperada.

INTRODUCTION: Respiratory viruses are the main cause of acute lower respiratory tract infection (ALRTI) in the pediatric population. In March 2020, the World Health Organization declared that the new coronavirus disease 2019 (COVID-19) had reached the pandemic status. Our objective was to describe the impact of COVID-19 pandemic on hospitalizations due to ALRTI at Hospital de Niños Ricardo Gutiérrez (HNRG) and virus circulation. METHODS: Observational, retrospective, and descriptive study of patients hospitalized due to ALRTI comparing 2019 and 2020. RESULTS: In 2020, the rate of hospitalization due to ALRTI decreased by 73%. In 2019, 517 patients with ALRTI were hospitalized; the following viruses were identified in 174: respiratory syncytial virus (RSV) (71.2%), adenovirus (AV) (10.3%), parainfluenza virus (PIV) (9.7%), and influenza virus (FLU) (8.6%). In 2020, 94 patients with ALRTI were hospitalized. Until epidemiological week (EW) 13, cases of ALRTI due to PIV and AV were recorded; in EW 29, there was 1 case of bronchiolitis due to AV and rhinovirus (RV), followed by isolated cases of RV; no ALRTI due to RSV or FLU was recorded. In total, 9 cases of ALRTI due to COVID-19 were recorded: 2 moderate bronchiolitis and 7 focal pneumonia; 1 adolescent with comorbidities died due to COVID-19 pneumonia. In 2020, patients were older and had more comorbidities and prior hospitalizations compared to 2019. Focal pneumonia prevailed. CONCLUSIONS: In 2020, the rate of hospitalization due to ALRTI decreased significantly compared to 2019, with the absence of seasonal respiratory virus circulation in the pediatric population.

Introducción. Los virus respiratorios son la principal causa de infección respiratoria aguda baja (IRAB) en la población pediátrica. En marzo de 2020, la Organización Mundial de la Salud declaró el estado de pandemia de la enfermedad por el nuevo coronavirus 2019 (COVID-19) con un impacto global elevado. El objetivo de este estudio fue describir el impacto de la pandemia de COVID-19 en las internaciones por IRAB en el Hospital de Niños Ricardo Gutiérrez (HNRG) y la circulación viral. Métodos. Estudio observacional, retrospectivo y descriptivo de pacientes internados por IRAB, comparando los años 2019 y 2020. Resultados. En 2020, la tasa de hospitalización por IRAB se redujo un 73 % en el HNRG (575,1/10 000 en 2019 y 155,3/10 000 en 2020). En 2019 se internaron 517 pacientes con IRAB; en 174 se identificaron los virus: sincicial respiratorio (71,2%), adenovirus (AV) (10,3%), parainfluenza (PIF) (9,7 %) e influenza (FLU) (8,6 %). En 2020, se hospitalizaron 94 pacientes con IRAB. Hasta la semana epidemiológica (SE) 13 se registraron casos de IRAB por PIF y AV; en la SE 29 un caso de bronquiolitis por AV y rinovirus (RV), seguido de casos aislados de RV; no hubo IRAB por VSR ni por FLU. Se registraron 9 casos de IRAB por COVID-19: 2 bronquiolitis moderadas y 7 neumonías focales; con un adolescente fallecido por neumonía por COVID-19 con comorbilidades. En 2020, los casos presentaron mayor edad, más comorbilidades e internaciones previas en comparación con el 2019. La neumonía focal fue la presentación clínica predominante. Conclusión. En 2020, la tasa de hospitalización por IRAB se redujo significativamente en comparación con el año anterior, con ausencia de circulación de virus respiratorios estacionales en la población asistida en nuestro centro.

Respiratory syncytial virus and influenza surveillance in schoolchildren seen at a children's hospital over 2 months of the second semester of 2021. / Vigilancia de virus sincicial respiratorio e influenza en niños escolarizados asistidos en un hospital pediátrico durante 2 meses del segundo semestre de 2021.

INTRODUCTION: Reporting of respiratory infections reduced during the COVID-19 pandemic. The objective was to estimate the prevalence of respiratory syncytial virus(RSV) and influenza in schoolchildren seen at a children's hospital during the return to school. METHODS: Cross-sectional study of patients aged 3-18 years suspected of COVID-19 with a negative test for SARS-CoV-2 between August and October 2021. Participants were stratified by level of education. PCR was used to detect RSV and influenza. RESULTS: A total of 619 children were included: 234 in pre-school, 224 in primary and 161 in secondary school; 25.5% (158) tested positive for RSV (36.3% in the pre-school level versus 21% in primary and 16% in secondary school). Infection among adolescents was associated with school contact with symptomatic cases (OR 2.5; 95%CI 1-6.80; p = 0.04). No case of influenza was detected. CONCLUSIONS: RSV was isolated in one fourth of the study population, with a higher frequency in pre-school; among adolescents, it was associated with school contact with symptomatic cases. No case of influenza was detected.

Introducción. Durante la pandemia de COVID-19, disminuyeron las notificaciones de infecciones respiratorias. El objetivo fue estimar la prevalencia de virus sincicial respiratorio (VSR) e influenza en niños escolarizados asistidos en un hospital pediátrico durante el retorno a la presencialidad. Métodos. Estudio transversal de casos sospechosos de COVID-19, de 3-18 años, con prueba negativa para SARS-CoV-2, entre agosto y octubre de 2021. Se estratificó por nivel educativo. Se utilizó PCR para detectar VSR e influenza. Resultados. Se incluyeron 619 niños: 234 del nivel inicial, 224 del primario y 161 del secundario; 25,5 % (158) fueron positivos para VSR (36,3 % del nivel inicial versus 21 % del primario y 16 % del secundario); en adolescentes se asoció la infección al contacto escolar con caso sintomático (OR 2,5; IC95%: 1-6,80; p = 0,04). No se aisló virus influenza. Conclusión. VSR se aisló en un cuarto de la población estudiada, con mayor frecuencia en el nivel inicial; en adolescentes, se asoció con contacto escolar sintomático. No se detectaron casos de influenza.