Cost of illness due to respiratory syncytial virus acute lower respiratory tract infection among infants hospitalized in Argentina

Acute lower respiratory tract infection (ALRTI) due to respiratory syncytial virus (RSV) is a main cause of hospitalizations and one of the most common causes of preventable post neonatal deaths in the world [1, 2]. Globally, it is responsible for over 33 million episodes of infection in children under five years old and is a leading disease diagnosed in hospital admissions with 3.2 million episodes per year in 2019 [1]. The disease burden is most prominent among the poorest and youngest children from low- and middle-income countries (LMICs) [3, 4]. Surprisingly, recent studies have shown that nearly 70% of the deaths in low-income economies countries occurred at home, outside any health facilities [1, 5‐8].

RSV disease among infants takes on added importance when considering the economic burden of illness [9]. Some estimations suggest that RSV accounts for 1.2 million discounted disability adjusted life-years (DALYs) and is associated with an economic toll of approximately €4.82 billion per year globally considering inpatients and outpatients under 5 years of age [9]. Most of this burden (65%) comes from LMICs, with almost 55% of global costs stemming from ALRTIs that require hospitalizations [9]. In addition, infants hospitalized due to RSV might require more complex care which leads to an increase in individual costs for health services [10].

Palivizumab (a monoclonal antibody against RSV F protein) was the first approved intervention for the prevention of severe ALRTI in pediatric patients [11]. Nevertheless, access to this prophylactic intervention is restricted in most LMICs. Some reasons are the high cost per dose, the difficulties in the administration logistics of several doses to achieve an efficacy close to 55%, and the recommendation for use which is limited to a specific subgroup of infants at very high risk [11‐13]. Nirsevimab, a monoclonal antibody with an extended half-life that allows administration as a single dose to cover the whole RSV season, was recently approved by the US Food and Drug Administration (FDA) for the prevention of RSV lower respiratory tract disease in neonates and infants, and in children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season [14, 15]. FDA has recently approved for US a vaccine for use in women during the middle of the third trimester of pregnancy to protect their babies against RSV up to 6 months after birth [16]. Moreover, many other vaccines and immune therapeutics technologies are also under clinical development and evaluation for children [17, 18].

In the scenario of new preventive interventions ahead, estimating the cost of illness (COI) for ALRTI due to RSV in LMICs is critical for several reasons [17]. First, most of the severe cases and deaths occur in these countries, where urgent implementation of preventive interventions is needed to diminish the impact of RSV disease. Second, COI studies provide relevant information on the economic burden of RSV and, therefore, the savings that could be achieved in the absence of RSV. Finally, COI studies can provide a more comprehensive understanding of the disease, including economic impact. A recent systematic review of COI for RSV identified three out of 44 costing studies conducted in LMICs and only one in Argentina, from the perspective of a private healthcare insurance [19, 20].

A gap in understanding remains around the economic impact of RSV episodes on previously healthy term infants attended in public hospitals in LMICs. This information is of special interest for stakeholders and decision makers to contribute setting priorities and guiding an evidence-based selection among available preventive interventions in contexts where resources are scarce. Therefore, the aim of this study was to determine the direct medical costs associated with ALRTI due to severe RSV disease in hospitalized infants in urban low-resource settings in Argentina.

In this study, we have defined the severe RSV-ALRTI direct medical cost of infants 12 months of age or below hospitalized in two public institutions of Buenos Aires, Argentina. We showed that the medical cost of RSV hospitalizations has a substantial economic impact in Argentina. Published literature suggests that the direct medical costs per RSV hospital admission episode vary widely between countries and regions. Results from this study are comparable with previous estimates in the city of Buenos Aires, Argentina (US$529) [37], Bogotá, Colombia ($518) [38], and several cities in South Africa ($681) [39]. Nevertheless, the costs presented in this study diverge from those documented in both high-income and low-income countries [9, 40, 41]. Likewise, in 2015, Marcone and colleagues computed the cost of hospitalizations attributed to ALRTI caused by viral agents, including influenza, within a private hospital [37]. They reported a median cost of US$529, a figure remarkably close to the US$514 reported in this study [37]. Several meta-analyses assessing costs associated with pneumonia, whether attributable to various causes or specific to RSV or other respiratory viruses, have indicated broad ranges of costs on a global and regional scale. Nevertheless, the average cost per hospitalization episode typically hovers around US$500 for Latin American countries or nations with GDP per capita comparable to that of Argentina (US$ 13,650 in 2022). Consequently, it may be more accurate to compare and categorize ALRTI hospitalization expenses among countries based on their respective GDP per capita.

In relation to the costs by categories established by the study, we found that the greatest determinant of the COI was the cost of health personnel involved in the hospitalized patients’ medical care, for both ward (65% of the total cost) and PICU patients (64% of the mean total cost). This finding could be explained on the basis of specific measures regarding drugs acquisition by the state and low prices of diagnostic methods [42]. Since 2002, to increase access to pharmaceuticals for patients attending public health centers in the country, the Argentinean government has been implementing a program called "Remediar" [43]. This program involves state centralized acquisition of more than 40 essential multi-source medicines (in several presentations), which generates more than 75% of cost saving in commonly used medicines with respect to their market price [42].

Even though, Argentina is classified as an upper-middle income country by the World Bank [44], the study population had remarkably contrasted socioeconomic status in comparison with other parts of the country. We found that most of the study families lived under the poverty line based on the established Argentinean government thresholds [6, 32, 33, 45]. Ninety-five percent of the families did not have medical insurance and accessed public health care institutions mainly by public transportation [33]. Additionally, we found a soaring rate of incomplete parental education and high rate of poor living conditions.

This study had several limitations. First, the research focused on estimating the health costs related to hospitalized patients due to RSV-ALRTI and not to outpatients. We consider this an important issue for future studies since the greatest burden of RSV disease occurs at the outpatient level. Second, the social perspective was not considered as part of the study to avoid recall bias since economic burden was estimated retrospectively. Third, the overhead costs might be slightly underestimated in this study, mainly after the diversification of payments for services by various parties such as the municipality (local county administration), the ministry of health (regional state system), social security institutions, and other intermediaries. Fourth, the estimations of the annual economic burden due to RSV hospitalizations in the country were derived from only two public facilities located in Buenos Aires; therefore, inferences may not be representative to other regions in Argentina. Finally, this study has focused on determining the health costs only for the public health system; therefore, costs associated with RSV in the private health and social security systems might be significantly higher than in the public health system.

In conclusion, this study described in detail the hospital cost and economic burden of RSV-ALRTI in infants under 12 months of age in Buenos Aires, Argentina. The medical costs associated with severe ALRTI due to RSV reported in this study were substantial for the public health system of Argentina. Not surprisingly, the medical costs shown were comparable with previous reports from other middle-income countries [37‐39, 46]. A detailed quantification of RSV-cost of illness is key for decision making, prioritizing future preventive interventions, and achieving effective allocation of health resources. Moreover, these data could be useful for estimating the full value of potentially avertable burden by vaccination [40]. Additionally, the information on cost categories reported in this study might enable policy makers and stakeholders to improve resource allocation strategies at health facilities. Further studies should explore the societal perspective, the outpatient economic burden of disease, and the impact of RSV in the country’s private sector.