Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infections in children, representing a major public health concern globally. Country-specific RSV seasonality reports found that its epidemics usually start in countries from the Southern Hemisphere between March and June and in countries in the Northern Hemisphere between September and December (1–3). Post-pandemic, there has been a notable increase in reported cases of RSV infections and co-circulation of other respiratory viruses, accompanied by shifts in epidemiology, altered respiratory season timing, and increased healthcare demand (4, 5).

Latin America and the Caribbean (LAC) have encountered a parallel situation, intensifying the burden on an already vulnerable pediatric population struggling with socio-economic disparities, low education rates, limited access to medical care, lack of appropriate infra-structure for supportive management of severe cases, irregular migration status, and native communities limitations, among other challenges (6, 7).

Low- and middle-income countries, where most mortality from respiratory illnesses occurs, are responsible for the highest burden of RSV disease, contributing significantly to health expenses during respiratory seasons, both in outpatient and inpatient settings (8). The approach to treat RSV infection is primarily centered on supportive measures (9), and until recently, preventive interventions like palivizumab were limited for high-risk populations. However, despite the positive cost-effectiveness associated with preventive measures for premature newborns and infants with underlying conditions, no real global epidemiological impact to reduce burden of disease has been identified, mainly associated to difficulties up taking measurements like palivizumab due to high cost, difficulty of monthly administration, and financial discrepancies among countries in the LAC region (10).

Advances in new strategies for the prevention of infection with long-acting monoclonal antibodies during the neonatal period and vaccination of pregnant women are now a reality. In November 2022, the European Medicine Agency (EMA) approved nirsevimab, a long-acting, single-dose, monoclonal antibody for the prevention of RSV infection in newborns and infants, which was subsequently approved by the Food and Drug Administration (FDA) in August 2023. In the same year, the FDA also approved the use of an RSV preF vaccine for pregnant women, offering an alternative tool for the prevention of this global health concern (11). In LAC countries, these novel interventions have been approved in Brazil, Chile, and Argentina.

This review aims to evaluate the burden of RSV infection in LAC region and analyze possible strategies to prevent RSV infection in children, to accomplish a reduction of morbidity and mortality associated with respiratory infections and avoid the known deleterious effect of RSV in children's pulmonary health.

Given the global burden of RSV infection, various pharmacological preventive tools have been extensively researched. The regional expert group of the Latin American Pediatric Infectious Diseases Society (SLIPE), started in 2023 an analysis of the current published information regarding RSV preventive measures for infants, including long-lasting monoclonal antibody and vaccination for pregnant women. Literature including data from pre-clinical studies to phase III and IV clinical trials, to recommendations of international societies of the different measures where analyzed. After a period of individual review of available literature, the expert group conducted a series of meetings that lead to this document with an overview of the disease, highlights of different strategies, and a series of recommendations for implementing new strategies for preventing RSV infection in the LAC region.

Several indicators can measure the impact of RSV infection in children, including morbidity, hospitalization rates, direct and indirect costs, and other related variables in patients and families (1, 2). In 2019, the estimated global rate of LRTI caused by RSV was 48.8 cases per 1,000 children under 5 years of age, with approximately 33 million cases annually. Notably, 20% of these cases occur in infants under 6 months of age, particularly in low- and middle-income countries (LMICs) (6).

Despite higher incidence in the community, the RSV-associated LRTI hospital admission rate in LMICs was similar to that in high-income countries for children aged 0–60 months, and for children aged 0–6 months. Also, hospital admission rate in LMICs was consistently lower than that in high-income countries (6).

In 2019, more than 100,000 of the 52 million deaths due to all causes were attributable to RSV in children younger than 5 years of age, with higher proportion in those younger than 6 months of age (6). Mortality rate linked to RSV infection is directly correlated with economic income, especially affecting those under 1 year of age. Alarmingly, more than 97% of these deaths occur in low- and middle-income countries, with almost 80% occurring outside hospital settings (6).

There are widespread differences in the incidence of the disease, hospitalizations, and mortality can be attributed to various factors, including prevention policies, inadequate surveillance, underreported cases, difficulties in accessing medical attention, and resource availability in hospital settings.

The economic burden of RSV disease exhibits significant variations between countries. A systematic review by Zhang et al. (8) revealed that, for hospitalization in high-income countries, costs can range from 850 to 33,385 USD, with a mean length of hospitalization of 3 days (95% CI 3.03–3.15). In middle-income countries, these costs decrease to 87–634 USD per episode, with a length of stay of 6.4 days (95% CI 6.36–6.46). Costs for patients without hospitalization vary between 254 and 1,131 USD in high-income countries and 63 to 334 USD in middle-income countries. Interestingly, African, and LAC data were not included in this analysis (8). Another systematic review on the economic burden of RSV infection in middle- or high-income countries (including China, Malaysia, Mexico, and Colombia) during 2022, reported total costs ranging from 709 to 3,815 USD. Although the main causes of expenses lack consensus, it is established that treatment represents almost 30% of the total price of medical care (12).

In LAC, a systematic review conducted in 2022 identified high incidence rates of RSV infection in the region. Argentina reported a rate of 47.5 cases per 1,000 children per year, and Panama documented an incidence of 52.2 cases per 1,000 children (4). In Argentina, by 2019, it was observed that more than 60% of hospitalizations were in children younger than 12 months of age (35.3% in less than 6 months, 26.9% in 6–12 months, 19.5% in 12–24 months, and 18.1% older than 24 months), with similar findings in other LAC countries (Table 1) (6, 13, 14).

Outcomes of disease exhibit variations based on age, revealing elevated admission rates to Pediatric Intensive Care Units (PICUs) in healthy children below 2 years old (14, 15). A Colombian trial reported a severity rate of 17.2%, identifying risk factors for ventilatory failure, including age younger than 6 months (OR: 4.58; 95% CI: 1.06–19.79; p = 0.041), low income (OR: 1.78; 95% CI: 1.06–2.99; p = 0.028), and malnutrition (OR: 3.99; 95% CI: 1.25–12.72; p = 0.019) (16), as observed in other LAC cohorts (14, 15). Mexico reported PICU admission rates ranging from 3.9% to 4.8% of all hospitalized cases (15, 17). In Argentina, it has been identified that 71.8% of all LRTI admissions to PICU were attributed to RSV (14).

The COVID-19 pandemic and the preventive measures (lockdowns, use of masks, and intensive hand hygiene) had a direct impact on respiratory virus circulation, including RSV (18, 19). In 2020–2021, a significant decrease in incidence, hospitalization, and mortality occurred in children under 5 years worldwide (20, 21). By 2021–2022, when most countries began withdrawing measures, a shift in seasonality was observed worldwide, with 2022–2023 cases being more comparable to previous seasons, yet respiratory infections season globally commenced earlier than anticipated (4, 22). Between 2019 and 22, the Public Health Institute in Chile documented RSV positivity rates of 25.2%, 0.2%, 10.3%, and 27.2% per year, respectively, aligning with global observations of viral circulation (23). This altered seasonality impacted the implementation of immune prevention strategies, resulting in higher hospitalization rates among high-risk patients (24). Also, an increase in age of affected children and the possibility of long-term sequelae associated has been documented, showing the need on availability of preventive measurements (25, 26).

Palivizumab (Synagis, Sobi, Inc, United States), a monoclonal antibody produced by recombinant DNA technology, was approved in 1998 for preventing severe LRTI due to RSV infection in high-risk pediatric populations, with proven safety and tolerability (27, 28). A multicenter observational study in LAC from 2011 to 2012 reported low RSV-related hospitalization rates in high-risk infants who received palivizumab according to routine clinical practice, endorsing the effectiveness and safety of palivizumab prophylaxis in the region (29). Nevertheless, this strategy has limitations, including high cost and limitations in real scenarios to complete all doses required of the monoclonal therapy to complete immunization. Switch to new preventive tools is recommended, but while countries acquire new measures, use of palivizumab is still recommended for high-risk infants.

RSV infection poses significant morbidity and mortality in children, especially among vulnerable groups, and it is associated with bacterial invasive infections, excessive antibiotic use, increased prescription of bronchodilators and steroids.

Based on the detrimental impact of RSV infection on medium- and long-term pulmonary health, the Regional Expert Group of the Latin American Pediatric Infectious Diseases Society (SLIPE) provides expert-based recommendations for implementing new strategies for preventing RSV infection in children in LAC region. 1.

Health authorities and decision makers in LAC region are strongly encouraged to adopt preventive strategies against RSV infection. These involve the implementation of vaccination against RSV during pregnancy, use of long-acting monoclonal antibodies, or a combined strategy (vaccination during pregnancy and availability of monoclonal antibodies for those born from non-vaccinated women as well as premature infants)

RSV infection stands as the leading cause of LRTI in children. It is important to emphasize that, despite the presence of well-known risk factors associated with more severe RSV infection, 70%–80% of hospitalizations and deaths associated with RSV occur in previously healthy, full-term born children. Recent approval of new preventive measures, such as a single-dose long-acting monoclonal antibody and maternal RSV preF vaccination, represents a unique opportunity to at last effectively prevent severe RSV-LRTI in infants, reducing the dramatic burden associated with this infection in infants. Given the worldwide prevalence of RSV infection, implementation of these strategies must be a priority in all countries, particularly in LMIC from LAC, where RSV represents a major public health concern. Equitable access to these new strategies for the prevention of severe lower respiratory tract infection caused by respiratory syncytial virus in infants is a clear demand. In this context, improving RSV surveillance in LAC countries, with quality information, will be of paramount importance to inform future implementation of immunization programs in the region.