Costs and cost-effectiveness of influenza illness and vaccination in low- and middle-income countries: A systematic review from 2012 to 2022

Abstract

Background: Historically, lack of data on cost-effectiveness of influenza vaccination has been identified as a barrier to vaccine use in low- and middle-income countries. We conducted a systematic review of economic evaluations describing (1) costs of influenza illness; (2) costs of influenza vaccination programs; and (3) vaccination cost-effectiveness from low- and middle-income countries to assess if gaps persist that could hinder global implementation of influenza vaccination programs.

Methods and findings: We performed a systematic search in Medline, Embase, Cochrane Library, CINAHL, and Scopus in January 2022 and October 2023 using a combination of the following key words: "influenza" AND "cost" OR "economic." The search included studies with publication years 2012 through 2022. Studies were eligible if they (1) presented original, peer-reviewed findings on cost of illness, cost of vaccination program, or cost-effectiveness of vaccination for seasonal influenza; and (2) included data for at least 1 low- or middle-income country. We abstracted general study characteristics and data specific to each of the 3 study types. Of 54 included studies, 26 presented data on cost-effectiveness, 24 on cost-of-illness, and 5 on program costs. Represented countries were classified as upper-middle income (UMIC; n = 12), lower-middle income (LMIC; n = 7), and low-income (LIC; n = 3). The most evaluated target groups were children (n = 26 studies), older adults (n = 17), and persons with chronic medical conditions (n = 12); fewer studies evaluated pregnant persons (n = 9), healthcare workers (n = 5), and persons in congregate living settings (n = 1). Costs-of-illness were generally higher in UMICs than in LMICs/LICs; however, the highest national economic burden, as a percent of gross domestic product and national health expenditure, was reported from an LIC. Among studies that evaluated the cost-effectiveness of influenza vaccine introduction, most (88%) interpreted at least 1 scenario per target group as either cost-effective or cost-saving, based on thresholds designated in the study. Key limitations of this work included (1) heterogeneity across included studies; (2) restrictiveness of the inclusion criteria used; and (3) potential for missed influenza burden from use of sentinel surveillance systems.

Conclusions: The 54 studies identified in this review suggest an increased momentum to generate economic evidence about influenza illness and vaccination from low- and middle-income countries during 2012 to 2022. However, given that we observed substantial heterogeneity, continued evaluation of the economic burden of influenza illness and costs/cost-effectiveness of influenza vaccination, particularly in LICs and among underrepresented target groups (e.g., healthcare workers and pregnant persons), is needed. Use of standardized methodology could facilitate pooling across settings and knowledge sharing to strengthen global influenza vaccination programs.

Fig 1. PRISMA flow diagram of study selection process.

ILI, influenza-like illness; SARI, severe acute respiratory infection.

Fig 2. Total costs-per-episode¹ of influenza illness, by disease severity (outpatient vs. hospitalized)², income group, and Strategic Advisory Committee of Experts on Immunization (SAGE) target group³, in low- and middle-income countries.

Plot representation: The horizontal line inside the box represents the median. The lower and upper borders of the box represent the 25th and 75th percentiles, respectively. The whiskers indicate 1.5 times the interquartile range from the lower and upper borders of the box. The cost-per-episode¹ reported in each study is depicted as a filled dot. Costs from low-income and lower-middle income countries are combined as 1 group (“LMIC/LIC”) and shown in magenta; costs from upper-middle income countries are in blue. The group “Children” is inclusive of children aged <18 years; “Older adults” is inclusive of adults aged ≥60 years. All costs are presented in 2022 US$. LIC, low-income country; LMIC, lower-middle income country; UMIC, upper-middle income country; US$, US Dollars. ¹Total costs inclusive of direct and indirect costs; direct costs were all medical and non-medical costs directly attributable to patient care. Indirect costs were all costs not directly attributable to patient care (e.g., lost earnings or lost productivity). Median costs were preferentially abstracted from source publications; if unavailable, mean costs were abstracted. ²No included papers reported hospitalization costs for older adults or persons with chronic medical conditions in LMIC/LIC. ³No cost-of-illness papers were identified for healthcare workers or individuals in congregate living settings in low- and middle-income countries.

Fig 3. Cost-effectiveness results of studies evaluating influenza vaccination¹, by Strategic Advisory Committee of Experts on Immunization (SAGE) target group, in low- and middle-income countries.

Plot representation: Bars represent the number of studies identified by target group and income group. Results from low-income and lower-middle income countries are combined and analyzed as 1 group, designated “LMIC/LIC.” Dark blue bars depict the number of studies that interpreted a result as “cost-saving,” light blue bars depict the number of studies that interpreted a result as “cost-effective,” and magenta bars depict the number of studies that interpreted a result as not cost-effective. Categorization is based on the interpretation provided in the original study; if any modeled intervention was interpreted as cost-saving (ICER<0), the study was characterized as “cost-saving” and if any modeled intervention was interpreted as cost-effective, the study was characterized as “cost-effective.” Interpretations of highly cost-effective and cost-effective were both combined as “cost-effective.” Details on each modeled scenario are provided in S5 Table. The group “Children” is inclusive of children aged <18 years; “Older adults” is inclusive of adults aged ≥60 years. LIC, low-income country; LMIC, lower-middle income country; UMIC, upper-middle income country. ¹Only includes studies comparing cost-effectiveness of influenza vaccination vs. no vaccination. Additional studies examining cost-effectiveness of modifications to a current vaccination program (e.g., increased coverage) are described in S5 Table.