Cost-utility analysis of palivizumab for preventing respiratory syncytial virus in preterm neonates and infants in Colombia.

AIM: Palivizumab has proven effective in reducing hospitalizations, preventing severe illness, improving health outcomes, and reducing healthcare costs for infants at risk of respiratory syncytial virus (RSV) infection. We aim to assess the value of palivizumab in preventing RSV infection in high-risk infants in Colombia, where RSV poses a significant threat, causing severe respiratory illness and hospitalizations. METHODS: We conducted a decision tree analysis to compare five doses of palivizumab with no palivizumab. The study considered three population groups: preterm neonates (≤ 35 weeks gestational age), infants with bronchopulmonary dysplasia (BPD), and infants with hemodynamically significant congenital heart disease (CHD). We obtained clinical efficacy data from IMpact-RSV and Cardiac Synagis trials, while we derived neonatal hospitalization risks from the SENTINEL-1 study. We based hospitalization and recurrent wheezing management costs on Colombian analyses and validated them by experts. We estimated incremental cost-effectiveness ratios and performed 1,000 Monte Carlo simulations for probabilistic sensitivity analyses. RESULTS: Palivizumab is a dominant strategy for preventing RSV infection in preterm neonates and infants with BPD and CHD. Its high efficacy (78% in preventing RSV in preterm infants), the substantial risk of illness and hospitalization, and the high costs associated with hospitalization, particularly in neonatal intensive care settings, support this finding. The scatter plots and willingness-to-pay curves align with these results. CONCLUSION: Palivizumab is a cost-saving strategy in Colombia, effectively preventing RSV infection in preterm neonates and infants with BPD and CHD by reducing hospitalizations and lowering healthcare costs.

Exploratory analysis of the economically justifiable price of nirsevimab for healthy late-preterm and term infants in Colombia.

INTRODUCTION: Respiratory syncytial virus infection is the leading cause of lower respiratory infection globally. Recently, nirsevimab has been approved to prevent respiratory syncytial virus (RSV) infection. This study explores the economically justifiable price of nirsevimab for preventing RSV infection in Colombia's children under 1 year of age. MATERIALS AND METHODS: A static model was developed using the decision tree microsimulation to estimate the quality-adjusted costs and life years of two interventions: a single intramuscular dose of nirsevimab versus not applying nirsevimab. This analysis was made during a time horizon of 1 year and from a societal perspective. RESULTS: The annual savings in Colombia associated with this cost per dose ranged from U$ 2.5 to 4.1 million. Based on thresholds of U$ 4828, U$ 5128, and U$ 19 992 per QALY evaluated in this study, we established economically justifiable drug acquisition prices of U$ 21.88, U$ 25.04, and U$ 44.02 per dose of nirsevimab. CONCLUSION: the economically justifiable cost for nirsevimab in Colombia is between U$ 21 to U$ 44 per dose, depending on the willingness to pay used to decide its implementation. This result should encourage more studies in the region that optimize decision-making processes when incorporating this drug into the health plans of each country.

A molecular perspective for the development of antibodies against the human respiratory syncytial virus.

The human respiratory syncytial virus (hRSV) is the leading etiologic agent causing respiratory infections in infants, children, older adults, and patients with comorbidities. Sixty-seven years have passed since the discovery of hRSV, and only a few successful mitigation or treatment tools have been developed against this virus. One of these is immunotherapy with monoclonal antibodies against structural proteins of the virus, such as Palivizumab, the first prophylactic approach approved by the Food and Drug Administration (FDA) of the USA. In this article, we discuss different strategies for the prevention and treatment of hRSV infection, focusing on the molecular mechanisms against each target that underly the rational design of antibodies against hRSV. At the same time, we describe the latest results regarding currently approved therapies against hRSV and the challenges associated with developing new candidates.

Palivizumabe para prevenção da infecção pelo vírus sincicial respiratório em crianças prematuras com idade gestacional de 29 a 31 semanas e seis dias / Palivizumab for prevention of respiratory syncytial virus infection in premature babies with gestational age from 29 to 31 weeks and six days

INTRODUÇÃO: O vírus sincicial respiratório (VSR) é um dos principais agentes etiológicos das infecções que acometem o trato respiratório inferior entre lactentes e crianças menores de 2 anos de idade. Durante os períodos de sazonalidade é responsável por até 75% das bronquiolites e 40% das pneumonias. Lactentes com menos de seis meses de idade, em especial, os prematuros, crianças com doença pulmonar crônica da prematuridade e cardiopatas, compõem a população de maior risco para desenvolver infecção respiratória grave, necessitando de internação por desconforto respiratório agudo em 10% a 15% dos casos. Em dados atuais obtidos no período de temperaturas mais baixas nos Estados Unidos (novembro de 2022 a fevereiro de 2023), a taxa global de hospitalização associada ao VSR, teve um pico de 65,3 hospitalizações por 100.000 indivíduos na faixa etária de zero a quatro anos, com maior incidência na faixa de zero a seis meses (255 por 100 mil indivíduos). Não há terapêutica específica que possa reduzir o tempo de infecção ou resolver os sintomas. O tratamento estabelecido é de suporte. HISTÓRICO DE RECOMENDAÇÃO DA CONITEC: Em 2012, a pedido da Justiça Federal da 4ª região (seção judiciária do Rio Grande do Sul), p

RSV through the COVID-19 pandemic: Burden, shifting epidemiology, and implications for the future.

Respiratory syncytial virus (RSV) represents a major global healthcare burden, particularly in those under 5 years of age. There is no available vaccine, with treatment limited to supportive care or palivizumab for high-risk children. Additionally, although a causal relationship has not been established, RSV has been associated with the development of asthma or wheezing in some children. The COVID-19 pandemic and the introduction of nonpharmaceutical interventions (NPIs) have caused substantial changes to RSV seasonality and epidemiology. Many countries have experienced an absence of RSV during the time of a typical season, followed by an out-of-season surge upon relaxation of NPI use. These dynamics have disrupted traditional RSV disease patterns and assumptions, but also provide a unique opportunity to learn more about the transmission of RSV and other respiratory viruses, as well as inform future approaches to RSV preventive strategies. Here, we review the RSV burden and epidemiology through the COVID-19 pandemic and discuss how new data may affect future decisions regarding RSV prevention.

Current strategies and perspectives for active and passive immunization against Respiratory Syncytial Virus in childhood.

OBJECTIVES: Despite the global impact of the Respiratory Syncytial Virus (RSV) infection in children, only one monoclonal antibody (Palivizumab) has been approved for clinical use. However, advances in the knowledge of RSV immunology may enable the development of safe and effective new vaccines and monoclonal antibodies in a few years. The purpose of this review is to summarize available data on approved and developing passive and active immunizations against RSV in childhood and pregnancy. DATA SOURCE: A non-systematic review of RSV immunoprophylaxis in childhood and pregnancy was carried out in PubMed, path.org and clinical trial registries, without language restrictions, up to September 2022. DATA SYNTHESIS: Three monoclonal antibodies and 17 active immunization candidates are under development in phase 1 to 3 clinical studies. Regarding the first group, Nirsevimab is a monoclonal antibody with a prolonged half-life whose approval for clinical use is expected in the next months. Among the vaccines under development, six techniques are being used: protein subunit, viral particles, live attenuated virus, recombinant viral vector, chimeric, and mRNA. The first two approaches are being tested primarily in pregnancy, while the others are being developed for the pediatric population. CONCLUSIONS: The approval of extended half-life monoclonal antibodies is the next expected advance in RSV prevention, although the costs may be a barrier to the implementation. Regarding active immunizations, maternal and infant vaccination are complementary strategies and there are many promising candidates in clinical studies using different platforms.

Impact of immunoprophylaxis with palivizumab on respiratory syncytial virus infection in preterm infants less than 35 weeks in Colombian hospitals.

OBJECTIVE: To evaluate the impact of immunoprophylaxis with palivizumab in preterm infants less than 35 weeks in terms of hospitalization rate, intensive care unit requirement, and mortality. METHODS: A prospective cohort study was conducted at six Colombian hospitals. Preterm infants less than 35 weeks who received at least one dose of palivizumab during the first 6 months of life were included. The primary outcome was the hospitalization rate related to respiratory syncytial virus (RSV) infection. RESULTS: A total of 222 newborns participated in the study; 204 (91.8%) completed the 6-month follow-up, and three died during the study. 88.7% received a second dose of palivizumab, 79.7% a third, 34.7% a fourth, and 25.2% a fifth. The nonadjusted incidence rate of RSV infection was 2.4%, and the overall RSV-positive hospitalization rate was 1.9%. The proportion of patients that required Neonatal Intensive Care Unit (NICU) and mechanical ventilation in relation to RSV infection was 1.4%. Discharge with home oxygen, pulmonary dysplasia, and being younger than 6 months were significantly associated with respiratory infection. Furthermore, exposition to cigarette smoke was the only factor associated with increased risk of hospitalization. The group that required hospitalization received fewer doses of palivizumab (p = 0.049). No discontinuation of treatment due to adverse events were reported. No death was judged to be related to palivizumab. CONCLUSION: The hospitalization rate and the need for NICU admission were lower than those reported in the literature. In this real-life setting, palivizumab appears to be effective in preventing serious cases of RSV infection.

Palivizumab for preventing severe respiratory syncytial virus (RSV) infection in children.

BACKGROUND: Respiratory viruses are the leading cause of lower respiratory tract infection (LRTI) and hospitalisation in infants and young children. Respiratory syncytial virus (RSV) is the main infectious agent in this population. Palivizumab is administered intramuscularly every month during five months in the first RSV season to prevent serious RSV LRTI in children. Given its high cost, it is essential to know if palivizumab continues to be effective in preventing severe RSV disease in children. OBJECTIVES: To assess the effects of palivizumab for preventing severe RSV infection in children. SEARCH METHODS: We searched CENTRAL, MEDLINE, three other databases and two trials registers to 14 October 2021, together with reference checking, citation searching and contact with study authors to identify additional studies. We searched Embase to October 2020, as we did not have access to this database for 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs), including cluster-RCTs, comparing palivizumab given at a dose of 15 mg/kg once a month (maximum five doses) with placebo, no intervention or standard care in children 0 to 24 months of age from both genders, regardless of RSV infection history.  DATA COLLECTION AND ANALYSIS: We used Cochrane's Screen4Me workflow to help assess the search results. Two review authors screened studies for selection, assessed risk of bias and extracted data. We used standard Cochrane methods. We used GRADE to assess the certainty of the evidence. The primary outcomes were hospitalisation due to RSV infection, all-cause mortality and adverse events. Secondary outcomes were hospitalisation due to respiratory-related illness, length of hospital stay, RSV infection, number of wheezing days, days of supplemental oxygen, intensive care unit length of stay and mechanical ventilation days. MAIN RESULTS: We included five studies with  a total of 3343 participants. All studies were parallel RCTs, assessing the effects of 15 mg/kg of palivizumab every month up to five months compared to placebo or no intervention in an outpatient setting, although one study also included hospitalised infants. Most of the included studies were conducted in children with a high risk of RSV infection due to comorbidities like bronchopulmonary dysplasia and congenital heart disease. The risk of bias of outcomes across all studies was similar and predominately low.  Palivizumab reduces hospitalisation due to RSV infection at two years' follow-up (risk ratio (RR) 0.44, 95% confidence interval (CI) 0.30 to 0.64; 5 studies, 3343 participants; high certainty evidence). Based on 98 hospitalisations per 1000 participants in the placebo group, this corresponds to 43 (29 to 62) per 1000 participants in the palivizumab group. Palivizumab probably results in little to no difference in mortality at two years' follow-up (RR 0.69, 95% CI 0.42 to 1.15; 5 studies, 3343 participants; moderate certainty evidence). Based on 23 deaths per 1000 participants in the placebo group, this corresponds to 16 (10 to 27) per 1000 participants in the palivizumab group. Palivizumab probably results in little to no difference in adverse events at 150 days' follow-up (RR 1.09, 95% CI 0.85 to 1.39; 3 studies, 2831 participants; moderate certainty evidence). Based on 84 cases per 1000 participants in the placebo group, this corresponds to 91 (71 to 117) per 1000 participants in the palivizumab group. Palivizumab probably results in a slight reduction in hospitalisation due to respiratory-related illness at two years' follow-up (RR 0.78, 95% CI 0.62 to 0.97; 5 studies, 3343 participants; moderate certainty evidence). Palivizumab may result in a large reduction in RSV infection at two years' follow-up (RR 0.33, 95% CI 0.20 to 0.55; 3 studies, 554 participants; low certainty evidence). Based on 195 cases of RSV infection per 1000 participants in the placebo group, this corresponds to 64 (39 to 107) per 1000 participants in the palivizumab group. Palivizumab also reduces the number of wheezing days at one year's follow-up (RR 0.39, 95% CI 0.35 to 0.44; 1 study, 429 participants; high certainty evidence). AUTHORS' CONCLUSIONS: The available evidence suggests that prophylaxis with palivizumab reduces hospitalisation due to RSV infection and results in little to no difference in mortality or adverse events. Moreover, palivizumab results in a slight reduction in hospitalisation due to respiratory-related illness and may result in a large reduction in RSV infections. Palivizumab also reduces the number of wheezing days. These results may be applicable to children with a high risk of RSV infection due to comorbidities. Further research is needed to establish the effect of palivizumab on children with other comorbidities known as risk factors for severe RSV disease (e.g. immune deficiencies) and other social determinants of the disease, including children living in low- and middle-income countries, tropical regions, children lacking breastfeeding, living in poverty, or members of families in overcrowded situations.

Risk factors for recurrent wheezing in preterm infants who received prophylaxis with palivizumab.

OBJECTIVE: To determine the prevalence of recurrent wheezing (RW) in preterm infants who received prophylaxis against severe infection with respiratory syncytial virus (RSV) and to identify genetic susceptibility (atopy or asthma) and risk factors for RW. METHODS: This was a cross-sectional study involving preterm infants who received prophylaxis with palivizumab at a referral center in Brazil during the first two years of age. A structured questionnaire was administered in a face-to-face interview with parents or legal guardians. RESULTS: The study included 410 preterm infants (median age = 9 months [0-24 months]). In the sample as a whole, 111 children (27.1%; [95% CI, 22.9-31.5]) had RW. The univariate analysis between the groups with and without RW showed no differences regarding the following variables: sex, ethnicity, maternal level of education, gestational age, birth weight, breastfeeding, number of children in the household, day care center attendance, pets in the household, and smoking caregiver. The prevalence of RW was twice as high among children with bronchopulmonary dysplasia (adjusted OR = 2.08; 95% CI, 1.11-3.89; p = 0.022) and almost five times as high among those with a personal/family history of atopy (adjusted OR = 4.96; 95% CI, 2.62-9.39; p < 0.001) as among those without these conditions. CONCLUSIONS: Preterm infants who received prophylaxis with palivizumab but have a personal/family history of atopy or bronchopulmonary dysplasia are more likely to have RW than do those without these conditions.

Eficacia y seguridad de palivizumab en la prevención de la enfermedad grave causada por el virus sincitial respiratorio en niños con displasia broncopulmonar y antecedente de prematuridad / Efficacy and safety of palivizumab in the prevention of severe respiratory syncytial virus disease in children with bronchopulmonary dysplasia and a history of prematurity

INTRODUCCIÓN: El presente dictamen expone la evaluación de la eficacia y seguridad de palivizumab para prevenir la enfermedad grave causada por el VSR en niños con DBP que hayan recibido tratamiento para la DBP en los últimos seis meses y tengan antecedente de haber nacido a las 29 semanas o menos de gestación. A nivel mundial, el virus sincitial respiratorio (VSR) es una de las principales causas de infección del tracto respiratorio inferior en niños. En Perú, el VSR ha sido detectado en el 86 % de niños menores de un año y en el 76 % de niños de uno a cuatro años, con infecciones respiratorias agudas. La displasia broncopulmonar (DBP) y la prematuridad son factores de riesgo para el desarrollo de enfermedad grave por VSR y están asociadas con mayores tasas de hospitalización, 388/1000 en niños con DBP y 57/1000 en niños prematuros, y muerte, tasas de casos fatales que van del 3.5 % al 23 % en niños con DBP y del 1.2 % al 6.1 % en niños prematuros. Un aspecto importante de la epidemiología del VSR es que difiere de acuerdo con las condiciones meteorológicas de las regiones. Por ejemplo, en las regiones tropicales y subtropicales, como es el caso de Perú, las infecciones por VSR se distribuyen de manera uniforme a lo largo de todo el año, con algunos aumentos variables. Actualmente, no se cuenta con un tratamiento antiviral efectivo para las infecciones por VSR, por lo que las medidas profilácticas toman gran importancia. Palivizumab, un anticuerpo monoclonal, es usado como una medida para prevenir el desarrollo de la enfermedad grave causada por el VSR, que requiera hospitalización, en niños susceptibles a desarrollar enfermedad. En el contexto de EsSalud, no se cuenta con una medida profiláctica frente a la enfermedad grave causada por el VSR. Los especialistas de EsSalud consideran que palivizumab ayudaría a prevenir la hospitalización, mortalidad y morbilidad causadas por la infección por VSR, en pacientes con alto riesgo de desarrollar enfermedad grave. En ese sentido, el presente dictamen expone la evaluación de la eficacia y seguridad de palivizumab, comparado con placebo, en la prevención de la enfermedad grave causada por el VSR en niños con DBP, que hayan recibido tratamiento para la DBP en los últimos seis meses, y con antecedente de haber nacido a las 29 semanas, o menos, de gestación. METODOLOGÍA: La búsqueda de la literatura se realizó con el objetivo de identificar evidencia sobre la eficacia y seguridad de palivizumab, en comparación con placebo, para prevenir la enfermedad grave causada por el VSR en niños con DBP que hayan recibido tratamiento para la DBP en los últimos seis meses, con antecedente de haber nacido a las 29 semanas o menos de gestación. La búsqueda de la evidencia se realizó en las bases de datos bibliográficas: PubMed, LILACS y The Cochrane Library. Adicionalmente, se amplió la búsqueda revisando la evidencia generada por grupos internacionales que realizan revisiones sistemáticas, evaluaciones de tecnologías sanitarias y guías de práctica clínica, tales como The National Institute for Health and Care Excellence (NICE), The Canadian Agency for Drugs and Technologies in Health (CADTH), Centro Nacional de Excelencia Tecnológica en Salud (CENETEC), Scottish Intercollegiate Guidelines Network (SIGN), Institute for Quality and Efficiency in Health Care (IQWiG), Scottish Medicines Consortium (SMC), Agency for Healthcare Research and Quality's (AHRQ), National Health and Medical Research Council (NHMRC), New Zealand Guidelines Group (NZGG), Canadian Medical Association (CMA), American College of Physicians Clinical Practice Guidelines y Registered Nurses Association of Ontario (RNAO). Adicionalmente, se realizó una búsqueda manual en las bases The Guidelines International Network (G-I-N), eGuidelines, y el portal de la Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA). Finalmente, se realizó una búsqueda manual en el portal ClinicalTrials.gov del National Institutes of Health (NIH) para identificar ensayos clínicos en desarrollo o cuyos resultados aún no hayan sido publicados en una revista científica. RESULTADOS: Se describe la evidencia disponible según el tipo de publicación, siguiendo lo indicado en los criterios de elegibilidad. CONCLUSIONES: En el presente documento, se evaluó la mejor evidencia científica disponible hasta agosto del 2021, en relación con la eficacia y seguridad de palivizumab en la prevención de la enfermedad grave causada por el VSR, que requiere hospitalización, en niños con DBP que hayan recibido tratamiento para la DBP en los últimos seis meses, con antecedente de haber nacido a las 29 semanas o menos de gestación. En EsSalud no se cuenta con una medida profiláctica frente al desarrollo de enfermedad grave causada por el VSR, que requiera hospitalización, para niños con alto riesgo; enmarcándose en un contexto de vacío terapéutico. La búsqueda sistemática de la evidencia culminó con la selección de dos GPC (Castaños y Rodríguez 2019; Ralston et al. 2014), dos ETS (Ministerio de Salud de Chile 2017; DIGEMID 2016), y el ECA de fase III IMPACT (The IMpact-RSV Study Group 1998). Las guías de Castaños y Rodríguez, y de Ralston et al., coinciden en recomendar la profilaxis con palivizumab en niños con DBP y prematuridad; aunque difieren en el rango de EG del paciente prematuro y el grado de DBP. Ambas guías tomaron en consideración los resultados del ECA IMPACT para emitir sus recomendaciones. Las dos ETS, del Ministerio de Salud de Chile y la DIGEMID de Perú, brindan recomendaciones opuestas sobre el uso profiláctico de palivizumab en niños con DBP y prematuridad. El Ministerio de Salud de Chile aprobó la ampliación de uso de palivizumab en pacientes prematuros menores a 36 semanas con patologías o condiciones de riesgo asociadas. En cambio, la DIGEMID de Perú decide no incluir a palivizumab en el PNUME para su uso en neonatos con EG de 29 a 32 semanas con DBP y edad corregida menor o igual a 3 meses al inicio de la profilaxis. Ambas ETS tomaron en cuenta los resultados del ECA IMPACT. El ECA IMPACT, evaluó el uso de palivizumab versus placebo en niños prematuros con edad menor o igual a seis meses, y niños con DBP y edad menor o igual a dos años. El ECA reportó la reducción de la incidencia de hospitalizaciones por VSR en los niños que recibieron palivizumab en comparación con placebo; un menor número de ingresos a UCI a favor de palivizumab. No se observaron diferencias en la incidencia de ventilación mecánica, duración de ventilación mecánica, mortalidad y el reporte de EA, entre el uso de placebo y palivizumab. El ECA IMPACT (estudio de fase III, doble ciego y pivotal de palivizumab) es el único ECA disponible que evalúa la eficacia comparativa de palivizumab. Las limitaciones del ECA IMPACT afectan la validez y precisión de sus resultados. Tomando en cuenta estas limitaciones, el uso de palivizumab sería eficaz en reducir la incidencia de hospitalización solo en el subgrupo de pacientes de 6 meses de edad o menos y prematuridad (EG menor o igual a 35 semanas). El contexto de vacío terapéutico y la evidencia disponible sugieren que el uso de palivizumab podría tener un impacto significativo en la incidencia de hospitalizaciones por VSR en la población objetivo del presente dictamen (pacientes con DBP y antecedente de prematuridad). Por lo expuesto, el IETSI aprueba el uso de palivizumab para la prevención de la enfermedad grave causada por el VSR en niños con DBP que hayan recibido tratamiento para la DBP en los últimos seis meses, con antecedente de haber nacido a las 29 semanas o menos de gestación, según lo establecido en el Anexo N°1. La vigencia del presente dictamen preliminar es de un año a partir de la fecha de publicación. Así, la continuación de dicha aprobación estará sujeta a la evaluación de los resultados obtenidos y de mayor evidencia que pueda surgir en el tiempo.

A post-incorporation study on the use of palivizumab in the Brazilian public health system.

Respiratory syncytial virus (RSV) is the main cause of lower respiratory disease in infants and children under five years of age. As there is no specific treatment for RSV infections, prophylaxis with the specific monoclonal antibody palivizumab (PVZ) has been widely recommended for high-risk cases during the RSV season. The present study aimed to evaluate the effectiveness of a public prophylaxis program with palivizumab on the incidence of hospitalizations for lower respiratory tract infections and RSV in children at high risk for severe RSV infections. A retrospective cohort study was carried out with preterm children or children under two years of age with chronic lung disease or hemodynamically significant congenital heart disease; the children were selected on the basis of their exposure status, which was defined as the prophylactic use of palivizumab during the RSV season. Children were enrolled retrospectively in two hospitals located in Southern Brazil, from May 2009 to August 2016. In a sample of 129 children, 69 (53.5%) received palivizumab and adherence to three or more doses was observed in 78%; 60 (46.5%) children did not receive palivizumab. PVZ prophylaxis was independently associated with a 66% reduction in hospitalizations for any cause (26/69 - 37.7%) in the PVZ group and 34/60 (56.7%) in the control group). A 52% reduction in hospitalizations due to lower respiratory tract infection was observed in the PVZ group (15/69 -21.7%) and 25/60 (41.7%) in the control group. These findings suggest that, for the group of studied patients, the adoption of an RSV prophylaxis scheme reached the same effectiveness as those described in previous clinical trials.

Risk factors for recurrent wheezing in preterm infants who received prophylaxis with palivizumab / Fatores de risco para sibilância recorrente em crianças pré-termo que receberam profilaxia com palivizumabe

ABSTRACT Objective: To determine the prevalence of recurrent wheezing (RW) in preterm infants who received prophylaxis against severe infection with respiratory syncytial virus (RSV) and to identify genetic susceptibility (atopy or asthma) and risk factors for RW. Methods: This was a cross-sectional study involving preterm infants who received prophylaxis with palivizumab at a referral center in Brazil during the first two years of age. A structured questionnaire was administered in a face-to-face interview with parents or legal guardians. Results: The study included 410 preterm infants (median age = 9 months [0-24 months]). In the sample as a whole, 111 children (27.1%; [95% CI, 22.9-31.5]) had RW. The univariate analysis between the groups with and without RW showed no differences regarding the following variables: sex, ethnicity, maternal level of education, gestational age, birth weight, breastfeeding, number of children in the household, day care center attendance, pets in the household, and smoking caregiver. The prevalence of RW was twice as high among children with bronchopulmonary dysplasia (adjusted OR = 2.08; 95% CI, 1.11-3.89; p = 0.022) and almost five times as high among those with a personal/family history of atopy (adjusted OR = 4.96; 95% CI, 2.62-9.39; p < 0.001) as among those without these conditions. Conclusions: Preterm infants who received prophylaxis with palivizumab but have a personal/family history of atopy or bronchopulmonary dysplasia are more likely to have RW than do those without these conditions.

RESUMO Objetivo: Determinar a prevalência de sibilância recorrente (SR) em crianças pré-termo que receberam profilaxia contra infecção grave pelo vírus sincicial respiratório (VSR) e identificar susceptibilidade genética (atopia ou asma) e fatores de risco para SR. Métodos: Estudo transversal envolvendo crianças pré-termo que receberam profilaxia com palivizumabe em um centro de referência no Brasil durante os primeiros dois anos de vida. Um questionário estruturado foi aplicado em entrevista presencial com os pais ou responsáveis. Resultados: O estudo incluiu 410 crianças pré-termo (mediana de idade = 9 meses [0-24 meses]). Na amostra total, 111 crianças (27,1%; IC95%: 22,9-31,5) apresentavam SR. A análise univariada entre os grupos com e sem SR não mostrou diferenças em relação às seguintes variáveis: sexo, etnia, escolaridade materna, idade gestacional, peso ao nascer, aleitamento materno, número de crianças no domicílio, frequência em creche, presença de animais de estimação no domicílio e cuidador tabagista. A prevalência de SR foi duas vezes maior entre crianças com displasia broncopulmonar (OR ajustada = 2,08; IC95%: 1,11-3,89; p = 0,022) e quase cinco vezes maior entre aquelas com história pessoal/familiar de atopia (OR ajustada = 4,96; IC95%: 2,62-9,39; p < 0,001) do que entre aquelas sem essas condições. Conclusões: Crianças pré-termo que receberam profilaxia com palivizumabe, mas apresentam história pessoal/familiar de atopia ou displasia broncopulmonar, têm maior probabilidade de apresentar SR do que aquelas sem essas condições.

RSV Lower Respiratory Tract Illness in Infants of Low- and Middle-income Countries.

This review addresses differences in respiratory syncytial virus (RSV) lower respiratory tract illness (LRTI) between industrialized and developing countries and provides observations associated with the dissimilar consequences of viral infection in both environments. RSV LRTI is an important cause of morbidity and mortality in infants worldwide. Its burden is highest in developing countries, where most hospitalizations and mortality occur. Palivizumab has been approved for disease prevention in premature infants in numerous countries but its cost and requirement for several doses hampers its routine use. The significant gap between low- and high-income countries in mortality rates stresses the need to identify specific risk factors for RSV LRTI prevention in different populations. CONCLUSION: RSV LTRI continues to be a serious problem for industrialised and developing countries, although mortality occurs preferentially in the latter. Several vaccines and monoclonal antibodies to prevent severe disease are advancing steadily in late phase trials. The next decade may witness a change in the landscape of RSV infections in young infants.

Pharmacological management of human respiratory syncytial virus infection.

INTRODUCTION: Human respiratory syncytial virus (hRSV) is the primary viral cause of respiratory diseases, leading to bronchiolitis and pneumonia in vulnerable populations. The only current treatment against this virus is palliative, and no efficient and specific vaccine against this pathogen is available. AREAS COVERED: The authors describe the disease symptoms caused by hRSV, the economic and social impact of this infection worldwide, and how this infection can be modulated using pharmacological treatments, preventing and limiting its dissemination. The authors discuss the use of antibodies as prophylactic tools -such as palivizumab- and the use of nonspecific drugs to decrease the symptoms associated with the infection -such as bronchodilators, corticoids, and antivirals. They also discuss current vaccine candidates, new prophylactic treatments, and new antivirals options, which are currently being tested. EXPERT OPINION: Today, many researchers are focused on developing different strategies to modulate the symptoms induced by hRSV. However, to achieve this, understanding how current treatments are working and their shortcomings needs to be further elucidated.

Seasonality and coinfection of bronchiolitis: epidemiological specificity and consequences in terms of prophylaxis in tropical climate.

OBJECTIVE: To describe the viruses involved, seasonality and coinfection in hospitalised children with suspected bronchiolitis. METHODS: Over the period 1/07/2007 to 31/12/2008, all children hospitalised for bronchiolitis in the paediatric ward were prospectively included, and had respiratory syncytial virus (RSV) screenings. We retrospectively tested all samples for RSVA, RSVB, rhinovirus (RV), human metapneumovirus, parainfluenza 1, 2, 3, 4, influenza A and influenza B. RESULTS: 198 children were tested, and 23% were negative for all viruses. RSVA was predominant in 2008 (64% of all viruses) and RSVB in 2007 (66% of all viruses). RV was frequent during both seasons (24% of all viruses). Flu was not found during the study period. Virus distribution was similar regardless of season or age, and identical to typical patterns in temperate countries. Coinfections were less frequent than in temperate regions because respiratory virus seasons seem to be better separated. The bronchiolitis season started in August and finished in December with a peak in October. CONCLUSION: The specific seasonality of bronchiolitis infection requires palivizumab prophylaxis starting in early July for high-risk infants.

OBJECTIF: Décrire les virus impliqués, la saisonnalité et la coinfection chez les enfants hospitalisés avec une suspicion de bronchiolite. MÉTHODES: Au cours de la période du 01/07/2007 au 31/12/2008, tous les enfants hospitalisés pour bronchiolite dans le service de pédiatrie ont été prospectivement inclus et soumis à un dépistage du virus respiratoire syncytial (VRS). Nous avons testé rétrospectivement tous les échantillons pour RSVA, RSVB, rhinovirus (RV), métapneumovirus humain, Parainfluenza 1, 2, 3, 4, Influenza A, et Influenza B. RÉSULTATS: 198 enfants ont été testés et 23% étaient négatifs pour tous les virus. RSVA était prédominant en 2008 (64% de tous les virus) et RSVB en 2007 (66% de tous les virus). RV était fréquent pendant les deux saisons (24% de tous les virus). La grippe n'a pas été trouvée pendant la période d'étude. La distribution des virus était similaire quelle que soit la saison ou l'âge, et identique aux modèles typiques dans les pays tempérés. Les coinfections étaient moins fréquentes que dans les régions tempérées car les saisons virales respiratoires semblent mieux séparées. La saison des bronchiolites a commencé en août et s'est terminée en décembre avec un pic en octobre. CONCLUSION: La saisonnalité spécifique de l'infection bronchiolite nécessite une prophylaxie au palivizumab débutant en juillet pour les nourrissons à haut risque.

Réévaluation des critères d'admissibilité au palivizumab (SynagisMC) pour la prévention des infections graves par le virus respiratoire syncytial chez l'enfant / Reassessment of palivizumab eligibility criteria (Synagis™) for the prevention of serious viral infections respiratory syncytial in children

INTRODUCTION: En vue d'optimiser l'usage du palivizumab et de déterminer ensuite le budget à y attribuer, le MSSS a demandé à l'INESSS de réviser les critères d'admissibilité du programme québécois d'immunoprophylaxie par le palivizumab. Le palivizumab (SynagisMC) est un agent d'immunisation passive, plus précisément un anticorps monoclonal humain (IgG1κ), qui agit en neutralisant le VRS et en inhibe la fusion avec la cellule. Il est commercialisé sous forme de solution pour injection par voie intramusculaire. Il est indiqué pour la « prévention d'affections graves des voies respiratoires inférieures causées par le virus respiratoire syncytial (VRS) chez les enfants hautement susceptibles de contracter une infection par le VRS. Soulignons que le palivizumab n'empêche pas la transmission du VRS; il influe plutôt sur le risque de voir une infection par le VRS s'aggraver au point d'entraîner une hospitalisation de l'enfant qui en est atteint. Le VRS est la principale cause d'affections des voies respiratoires inférieures, notamment la bronchiolite et la pneumonie, chez les jeunes enfants. Leur incidence est à son pic chez les nourrissons âgés de 2 à 6 mois et il infecte presque tous les enfants avant l'âge de 2 ans, lors d'épidémies annuelles sévissant généralement, au Québec, de la mi-novembre à la fin avril. Le traitement des enfants qui en sont atteints consiste principalement à soulager les symptômes. La primo-infection ne confère pas une immunité protectrice et, donc, une réinfection est possible durant la même saison ou les saisons subséquentes. Environ 1 à 2 % des enfants atteints de bronchiolite seront malades au point de devoir être hospitalisés afin de recevoir de l'oxygénothérapie ou des soins d'appoint. Les frais d'hospitalisation représentent plus de la moitié du fardeau économique associé au VRS chez les enfants âgés de moins de 4 ans. La documentation scientifique rapporte que certaines populations d'enfants risquent plus que d'autres d'être hospitalisées, de séjourner plus longtemps à l'hôpital ou d'être admises dans une unité de soins intensifs. Il s'agit notamment de certains bébés prématurés, d'enfants atteints de dysplasie bronchopulmonaire, de maladie pulmonaire chronique du nouveau-né ou d'une cardiopathie congénitale dont les conséquences hémodynamiques sont cliniquement significatives. Parmi les enfants hospitalisés, certains peuvent avoir des séquelles à long terme. Toutefois, les décès sont rares. Un programme d'immunoprophylaxie est en vigueur au Québec depuis plusieurs années. Il cible les populations pédiatriques jugées les plus à risque de complications en cas d'infection des voies respiratoires par le VRS. L'objectif du présent rapport est de faire état des recommandations de l'INESSS concernant la mise à jour des critères d'admissibilité à ce programme en vue de la saison 2020-2021 et des modalités d'administration du palivizumab, en tenant compte de l'évolution de la science et de la pratique clinique. MÉTHODOLOGIE: L'INESSS a procédé à des travaux relatifs à la réévaluation des critères d'admissibilité au palivizumab pour la prévention des infections graves des voies respiratoires par le VRS chez l'enfant. À cette fin, le cadre d'évaluation retenu s'inspire de celui établi relativement à l'évaluation des médicaments aux fins d'inscription sur les listes des médicaments assurés au Québec. En effet, il inclut les volets de la valeur thérapeutique, de la justesse du prix et du rapport entre le coût et l'efficacité du produit, des conséquences sur la santé de la population et sur les autres composantes du système de santé et des services sociaux et celui des autres considérations, notamment de nature éthique ou sociétale. Il s'agit d'une démarche rigoureuse qui permet de formuler des recommandations fondées sur des données scientifiques, en plus des données expérientielles des cliniciens et des parents d'enfants. Ainsi, cela augmente les chances que la communauté médicale adhère à ces recommandations et que la population soit réceptive aux changements, le cas échéant. JUSTESSE DU PRIX: Le prix de vente d'une fiole de 50 mg et de 100 mg de palivizumab est respectivement de 752,30 $ et de 1 504,50 $. En considérant une administration tous les mois pour une saison d'une durée de 5 mois, le coût de traitement du palivizumab est de 4 739 $ pour un bébé de 4,2 kg, soit le poids moyen des bébés inscrits au registre canadien du palivizumab (registre CARESS) pour les saisons 2013-2014 et 2014-2015. À noter que les pertes en médicament n'ont pas été considérées, compte tenu du fait qu'en pratique, les cliniciens administrent la prophylaxie en groupe chez les bébés afin d'éviter ces pertes. RAPPORT ENTRE LE COÛT ET L'EFFICACITÉ: Du point de vue pharmacoéconomique, compte tenu du fait que l'INESSS recommande le maintien de l'abrogation du critère d'admissibilité au palivizumab pour les bébés prématurés nés de 33 à 35 SG, à la suite de l'évaluation réalisée par les membres du groupe d'experts et du CSEMI, l'évaluation de l'efficience du produit n'a pas été réalisée. En ce qui concerne les autres critères d'admissibilité, lesquels portent notamment sur la population d'enfants du Nunavik nés à terme, ils sont tous maintenus. Il est important de souligner que lors de la réévaluation des critères d'admissibilité au palivizumab en août 2016, il n'avait pas été possible d'évaluer l'efficience de ce produit chez ces différentes populations. Cela s'expliquait notamment par la faiblesse ou l'absence de preuves cliniques suffisamment robustes pour être introduites dans le modèle pharmacoéconomique. À noter qu'en raison de constats similaires quant à la qualité des études analysées dans les présents travaux, il n'a pas été davantage possible d'évaluer l'efficience du palivizumab. CONCLUSION: Le mode d'évaluation qu'adopte usuellement l'INESSS pour les médicaments à inscrire sur les listes des médicaments présente des défis dans le cas d'un produit comme le palivizumab. Il s'est avéré que les études répertoriées sont, en grande majorité, des études rétrospectives de faible niveau de preuve, dont la plupart incluent un faible nombre de patients. De surcroît, l'usage du palivizumab n'est pas documenté en ce qui concerne certaines populations pédiatriques. L'INESSS, conformément à ses modalités d'évaluation des médicaments [INESSS 2018], a procédé à l'évaluation des données scientifiques à l'aide d'un groupe d'experts, et en considérant les données expérientielles rapportées par les parents. Parmi les recommandations finales résumées au début du rapport, l'INESSS souhaite, pour conclure, mettre l'accent sur les points suivants: La revue systématique indique une absence de données cliniques concernant certaines des populations ciblées, de même que la présence d'un très faible nombre d'études de qualité. La grande majorité des études répertoriées sont rétrospectives et de faible niveau de preuve; elles ont été effectuées à partir de dossiers médicaux ou de données de facturation. La plupart de ces études incluent un petit nombre de patients dont l'AG à la naissance est très variable. L'abrogation du critère concernant les bébés prématurés nés de 33 à 35 SG doit être maintenue. L'étude analysée, réalisée au Québec, présente trop de limites pour permettre de recommander la réintroduction d'un critère d'admissibilité pour ces enfants. Le critère d'admissibilité ciblant les enfants du Nunavik nés à terme doit être maintenu. Ce maintien doit s'accompagner d'améliorations du fonctionnement global du système : des ressources supplémentaires doivent être déployées afin d'assurer l'inclusion et l'acceptation des populations ciblées, d'optimiser l'implantation et l'adhésion au traitement, sans affecter les ressources dédiées aux autres programmes de santé publique. De plus, le financement dédié à l'évaluation de l'efficacité du palivizumab chez cette population devrait être prolongé. L'évaluation des répercussions personnelles et financières sur les familles et sur le système de santé (hospitalisations et transferts) est souhaitable. Par ailleurs, une meilleure coordination avec les membres des communautés devrait être mise de l'avant, de façon à optimiser la prophylaxie. L'INESSS préconise le maintien des modalités d'administration du palivizumab en vigueur, notamment la poursuite des mesures ayant pour but de favoriser l'efficacité du palivizumab. Compte tenu de la recommandation de maintien des critères d'admissibilité du palivizumab et de la qualité insuffisante des données répertoriées dans les présents travaux, il n'y a pas lieu d'effectuer une évaluation du rapport entre le coût et l'efficacité chez les différentes populations d'intérêt. L'impact financier net demeure nul puisque les coûts d'acquisition du palivizumab sont déjà engagés.

Respiratory syncytial virus acute respiratory infection-associated hospitalizations in preterm Mexican infants: A cohort study.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of severe acute respiratory infections (ARI) in preterm infants. The incidence of RSV-associated hospitalizations has not been defined in Mexico. OBJECTIVES: To determine the incidence of ARI- and RSV-associated hospitalizations in preterm infants during the first year of life. METHODS: Prospective cohort study of 294 preterm infants followed up through monthly telephone calls and routine outpatient visits. Hospitalized children were identified through daily visits to pediatric wards of participating hospitals and through telephone calls. Respiratory samples were tested for RSV by RT-PCR. RESULTS: Mean gestational age of participating infants was 33 weeks. Ninety-six infants were diagnosed with bronchopulmonary dysplasia (BPD) and 17 with congenital heart disease (CHD); 11 had both conditions. There were 71 hospitalization episodes in 53 infants. Respiratory samples for RSV detection were available in 44 hospitalization episodes, and the result was positive in 16 (36.3%). At least one hospitalization for ARI was recorded in 33 of 96 participants with BPD, in seven of 17 with CHD, and 18 of 192 infants without these diagnoses. Five (71.4%) of CHD infants who required admission also had BPD. RSV-confirmed hospitalization rates were 9.4%, 5.9%, and 2.6% for infants with BPD, CHD, and otherwise healthy preterm infants, respectively. Attributable RSV admission frequencies were estimated to be 13.6%, 16.5%, and 4.1%, respectively. CONCLUSIONS: Mexican preterm infants, particularly those with BPD, have high rates of ARI- and RSVassociated hospitalizations. Specific interventions to reduce the incidence of severe infections in this highrisk group are required.

TEMPORAL TREND OF HOSPITALIZATIONS FOR ACUTE BRONCHIOLITIS IN INFANTS UNDER ONE YEAR OF AGE IN BRAZIL BETWEEN 2008 AND 2015.

OBJECTIVE: To evaluate the trend of hospitalization for acute bronchiolitis in infants under one year of age, in the past eight years and after the implementation of the palivizumab immunization program in Brazil. METHODS: The study is a retrospective analysis of data on infants younger than one year of age, who were hospitalized with acute bronchiolitis between 2008 and 2015 in Brazil. The Brazilian National Health System database was used. The rates of hospitalization in the pre-implementation (2008-2012) and post-implementation (2014-2015) periods of the palivizumab immunization program were evaluated. The total number of admissions in the same period was used as a comparison. RESULTS: Between January 2008 and December 2015, 263,679 hospitalizations for bronchiolitis were recorded in infants younger than one year of age, 60% represented by boys. The incidence of hospitalization for bronchiolitis increased by 49% over this period (8.5 to 12.7 per 1,000 inhabitants per year). Between 2013 and 2014, the incidence rate of hospitalization for acute bronchiolitis decreased by 8% (12.5 to 11.5 per 1,000 inhabitants per year). However, in the second year of the program, hospitalization rate increased again by 10% (12.7 per 1,000 inhabitants per years). CONCLUSIONS: Acute bronchiolitis presented increasing rates of hospitalization over the study period. Hospitalization incidence for acute bronchiolitis declined one year after the implementation of palivizumab but increased again in the second year of the program.

Temporal trend of hospitalizations for acute bronchiolitis in infants under one year of age in brazil between 2008 and 2015 / Tendência temporal das hospitalizações por bronquiolite aguda em lactentes menores de um ano no brasil entre 2008 e 2015

ABSTRACT Objective: To evaluate the trend of hospitalization for acute bronchiolitis in infants under one year of age, in the past eight years and after the implementation of the palivizumab immunization program in Brazil. Methods: The study is a retrospective analysis of data on infants younger than one year of age, who were hospitalized with acute bronchiolitis between 2008 and 2015 in Brazil. The Brazilian National Health System database was used. The rates of hospitalization in the pre-implementation (2008-2012) and post-implementation (2014-2015) periods of the palivizumab immunization program were evaluated. The total number of admissions in the same period was used as a comparison. Results: Between January 2008 and December 2015, 263,679 hospitalizations for bronchiolitis were recorded in infants younger than one year of age, 60% represented by boys. The incidence of hospitalization for bronchiolitis increased by 49% over this period (8.5 to 12.7 per 1,000 inhabitants per year). Between 2013 and 2014, the incidence rate of hospitalization for acute bronchiolitis decreased by 8% (12.5 to 11.5 per 1,000 inhabitants per year). However, in the second year of the program, hospitalization rate increased again by 10% (12.7 per 1,000 inhabitants per years). Conclusions: Acute bronchiolitis presented increasing rates of hospitalization over the study period. Hospitalization incidence for acute bronchiolitis declined one year after the implementation of palivizumab but increased again in the second year of the program.

RESUMO Objetivo: Avaliar a tendência de hospitalização por bronquiolite aguda (BA) em lactentes menores de um ano de idade nos últimos oito anos no Brasil e, secundariamente, após a implementação do programa de imunização por palivizumabe. Métodos: Análise retrospectiva dos dados de lactentes menores de um ano de idade, hospitalizados com diagnóstico de BA entre 2008 e 2015 no Brasil, utilizando o banco de dados do Sistema Único de Saúde (SUS). Foram avaliadas as taxas de hospitalização nos períodos pré-implementação (2008-2012) e pós-implementação (2014-2015) do programa de imunização por palivizumabe. O número total de internações no mesmo período foi utilizado como comparação. Resultados: Entre janeiro de 2008 e dezembro 2015 foram registradas 263.679 internações por bronquiolite em lactentes menores de um ano de idade, 60% representado por meninos. A incidência de hospitalização por bronquiolite aumentou em 49% ao longo desse período (8,5 para 12,7 por mil ­habitantes/­ano). Entre 2013 e 2014, a taxa de incidência de hospitalização por BA diminuiu 8% (12,5 para 11,5 por mil habitantes/ano). Porém, no segundo ano do programa, a taxa de internação aumentou novamente em 10% (12,7 por mil habitantes/ano). Conclusões: A BA apresentou taxas de hospitalização crescente ao longo do período estudado. A incidência de hospitalizações de BA apresentou declínio um ano após a implementação de palivizumabe e retornou à tendência crescente no segundo ano do programa.

Palivizumab para prevenir infecciones respiratorias bajas por virus sincicial respiratorio / Palivizumab to prevent respiratory syncytial virus lower respiratory infections

CONTEXTO CLÍNICO: El virus sincicial respiratorio (VSR) es la causa más común de infecciones respiratorias en lactantes y niños pequeños en todo el mundo.1 Es un virus omnipresente que es contraído por todos los lactantes dentro de los primeros dos años de vida. El VSR produce infecciones respiratórias estacionales que son una causa significativa de morbilidad y mortalidad, principalmente, en los menores de un año. Se estima que el VSR causa hasta el 90% de las hospitalizaciones por bronquiolitis y hasta el 50% de las hospitalizaciones pediátricas por neumonía, siendo el principal patógeno en el lactantes y niños pequeños. En el estudio BOSTID realizado en países en desarrollo y que incluyó datos de Argentina, el VSR ocasionó el 70% de las infecciones respiratorias agudas bajas y las tasas de mortalidad fueron de hasta 7%. Diferentes estudios epidemiológicos demuestran que la infección primaria por VSR ocurre entre las seis semanas y los dos años de vida, con un pico máximo de incidencia entre los dos y seis meses, sibien en un estudio realizado en Argentina, sobre 805 niños internados con infecciones respiratória aguda baja (IRAB), el 11% tuvo menos de 1 mês. Presenta amplia difusión y contagiosidad y em todo el mundo puede demostrarse una incidencia estacional durante los meses de otoño e invierno. TECNOLOGÍA: Synagis® (palivizumab) es un anticuerpo monoclonal humanizado producido por tecnología de ADN recombinante, dirigido a un epítope en el sitio antigénico A de la proteína F del virus sincicial respiratorio. De esta forma, el palivizumab confiere inmunización pasiva contra el VSR. Palivizumab muestra actividad neutralizante e inhibitoria de la fusión contra el virus sincicial respiratorio (VSR). Se evita, así, la formación de sincicios y la adherencia al epitelio respiratorio una vez que el vírus infectó al huésped, lo que previene el desarrollo de formas bajas y/o graves. Palivizumab está indicado para la prevención de la enfermedad grave del tracto respiratorio inferior causada por el VSR en pacientes pediátricos con alto riesgo de enfermedad por VSR. OBJETIVO: El objetivo del presente informe es evaluar la evidencia disponible acerca de la eficacia, seguridad y aspectos relacionados a las políticas de cobertura del uso del palivizumab para la prevención de infecciones por VSR en pacientes pediátricos con riesgo de infecciones severas por VSR. MÉTODOS: Se realizó una búsqueda en las principales bases de datos bibliográficas, en buscadores genéricos de internet, y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas (RS), ensayos clínicos controlados aleatorizados (ECAs), evaluaciones de tecnologías sanitarias (ETS), evaluaciones económicas, guías de práctica clínica (GPC) y políticas de cobertura de diferentes sistemas de salud. RESULTADOS: Se incluyeron, tres RS, seis GPC, y 16 informes de políticas de cobertura de palivizumab en la profilaxis de infecciones respiratorias en pacientes con alto riesgo de infecciones severas por VSR. CONCLUSIONES: Evidencia de alta calidad muestra que el palivizumab es efectivo en la reducción del número de hospitalizaciones y de ingresos en terapia intensiva en pacientes prematuros y pacientes con cardiopatías congénitas hemodinámicamente significativas, aunque sin impacto en la mortalidad. Hay consenso en las guías de práctica clínica en la recomendación del uso de palivizumab durante la temporada de virus sincicial respiratorio en pacientes con alto riesgo de infecciones severas por este virus. Existen divergencias entre las guías en cuanto a los criterios que definen la población con indicación de palivizumab. La mayoría de los financiadores tanto públicos como privados de países de altos ingresos y de Latinoamérica recomiendan el uso de palivizumab, excepto en Australia en donde no se recomenda ya que el balance entre los beneficios y los costos no fue favorable para la incorporación de este fármaco. Existe una gran heterogeneidad entre las evaluaciones económicas en la determinación de la costo-efectividad del palivizumab, con algunos estudios mostrando que es una opción costo-ahorrativa, hasta estimaciones que consideran una razón de costo-efectividad incremental mayor a un millón de dólares por año de vida ajustado por calidad.