Influenza Vaccine-Averted Illness in Chile, Guyana, and Paraguay During 2013–2018: A Standardized Approach to Assess the Value of Vaccination
Study Population The study included young children and older adults in Chile and Paraguay during the influenza seasons from 2013 to 2018. In Chile, the target populations for the influenza vaccine include children aged 6–23 months and adults aged 65 years and older. In Paraguay, the target populations for the vaccine include children aged 6–23 months and adults aged 60 years and older. Guyana does not have a national influenza immunization program with defined target populations, nor is the influenza vaccine currently available in the private sector. For our estimation, we included the population estimates for children under 5 years old and adults aged 65 years and older during an average year, 2022. Study Design To estimate the impact of influenza vaccination, we used a static compartmental model adapted from Tokars et al , as previously described , with parameterized monthly estimates of influenza hospitalizations, vaccination coverage, and effectiveness of influenza vaccine. In countries like Chile and Paraguay, which have influenza immunization programs, the model compares influenza illness estimates under an observed vaccination scenario with modeled estimates of illness that would have occurred in the hypothetical absence of a vaccination campaign. In countries like Guyana, which do not yet have an influenza immunization program, the model compares influenza illness estimates with modeled estimates of illness that would have occurred in the hypothetical presence of a vaccination campaign. Additionally, we used the model to assess how increasing vaccine coverage and utilizing different vaccine deployment strategies would impact averted illness. Data Inputs and Sources Target Population The size of the target population was obtained from the National Institutes of Statistics (Instituto Nacional de Estadística) of Chile and Paraguay . We obtained the target population size for Guyana from the Department of Economic and Social Affairs, United Nations . Estimated Monthly Hospitalizations In Chile and Paraguay, to estimate monthly influenza-associated hospitalizations, we used hospital discharges for which the leading cause of admission was a respiratory system disease diagnosis corresponding to International Classification of Diseases-Tenth Revision (ICD-10) codes J00–J99, by age group. We used the percent positivity for influenza virus obtained from national virologic surveillance by dividing samples positive for any influenza virus by the total number of samples tested. We determined the month- and age-stratified percentage of samples testing positive for the influenza virus by dividing the number of positive samples by the total number of samples analyzed in the same month. For Guyana, which implemented influenza surveillance in 2023, we used influenza-associated hospitalization estimates previously obtained by Palekar et al  available for children younger than 5 years and adults 65 years and older. The total number of influenza hospitalizations were extrapolated from the incidence estimates using the country's total population as of 2022 (808 734 inhabitants, of which 78 980 were children under 5 years and 50 764 were adults aged 65 years and older). In the absence of Guyana's influenza case distribution, which was unavailable for the study period, we obtained the average monthly influenza distribution from 2010 to 2022 using influenza viral circulation distribution from neighboring countries—Suriname and French Guiana—available via FluNet . We used multipliers derived from a Peru study  for hospitalized to nonhospitalized influenza illnesses and the proportion of influenza-associated illnesses that were medically attended to transform influenza-associated hospitalizations into nonhospitalized illnesses (defined as mild to moderate symptomatic influenza illness that may be self-limiting or require outpatient/ambulatory medical care, but not hospitalization) and medically attended illnesses (defined as influenza illnesses requiring medical treatment, including hospitalization) for each age group. Vaccine Coverage and Vaccine Effectiveness The number of people vaccinated against influenza in Chile and Paraguay for each target population per season and month from 2013 to 2018 was collected from administrative influenza vaccination data, electronic records, or coverage surveys. We utilized unpublished data from the REVELAC-i regional influenza vaccine effectiveness estimates, which were calculated using a test-negative design in hospitalized young children (aged 6–24 months) and older adults (aged ≥60 years) in Argentina, Brazil, Chile, Colombia, Paraguay, and Uruguay. For Guyana, we specified vaccine coverage as 30% of the target population. We obtained vaccine effectiveness from a systematic review and meta-analysis published in 2021 for children under 5 years old  and adults aged 65 years and older during the 2017 influenza season . Given year-round circulation of influenza in Guyana, we considered the availability of vaccines for the Northern Hemisphere and the Southern Hemisphere. In the base scenario, the campaign reached 30% coverage over a 4-month campaign (5% coverage in month 1, 10% in month 2, 10% in month 3, 5% in month 4) starting in October (Northern Hemisphere formulation) or in March (Southern Hemisphere formulation). Analysis We used an Excel-based tool developed by PAHO, the World Health Organization, and the US Centers for Disease Control and Prevention (CDC) (PAHO internal document) to run the model, obtain the averted illness estimates, and analyze varying coverage and vaccine deployment scenarios. We calculated confidence intervals using R software through a Monte Carlo simulation of 5000 iterations. If the lower limit of the confidence intervals for vaccine effectiveness was negative, the limit was set to zero . The analytic methods have been previously described . Briefly, in countries with vaccination programs (ie, Chile and Paraguay), the model calculates the monthly incidence of influenza-associated cases by dividing the events observed each month by the population susceptible to that event in the previous month. The monthly susceptible population is estimated as the total population of the target group minus the population that developed influenza and the population effectively vaccinated that month. For the hypothetical scenario without the vaccine, the monthly incidence of influenza-associated cases is calculated, and the susceptible population is estimated as the total population minus only the population that developed influenza, month by month. For Guyana the number of influenza-associated hospitalizations that could have been prevented through vaccination was estimated as the difference between the observed number of hospitalizations in the absence of vaccination and the expected number of influenza-associated hospitalizations in the presence of vaccination. We present the results as the number of events averted by vaccination (ie, the number of nonhospitalized influenza illnesses, medically attended influenza illnesses, and influenza-associated hospitalizations) and as the prevented fraction of illnesses, estimated as the percentage of the illnesses averted among illnesses that would have occurred in the absence of vaccination. Additional Vaccine Deployment Scenarios To show the average annual effect of vaccination campaigns from 2013 to 2018, we calculated the vaccine's effectiveness for that period and monthly averages of hospitalizations and vaccinations. The median population for that period was also taken into consideration. In addition to the base model, we assessed the effect of increased coverage and different vaccine deployment strategies on the burden of disease averted. The analysis of increased coverage included 40%, 60%, 70%, 75%, 80%, and 90% vaccine coverage. The analysis of campaign deployment scenarios included 3 strategies: in strategy 1, the observed coverage would be achieved in 3 months with the start of the campaign in March (70%, 20%, and 10% of observed coverage in the first, second, and third month, respectively); in strategy 2, the observed coverage would be achieved in 3 months with the start in February (70%, 20%, 10% of observed coverage); and in strategy 3, the observed coverage would be achieved in 2 months with the start in February (80%, 20% of observed coverage). For Guyana, the baseline scenario used the Northern Hemisphere vaccine and the campaign reached 30% coverage over a 4-month campaign starting in October (5%, 10%, 10%, 5%). The alternative scenarios increased the total coverage to 40%, 50%, 60%, and 70%. We defined 4 alternative deployment strategies. In strategies 1 to 3, the campaign would last 3 months, reaching 50%, 30%, and 20% of the coverage in each consecutive month, but the beginning of the campaign was delayed in the second (November) and third strategies (December). In the fourth strategy, the campaign begins in October, but lasts 10 months, with the same monthly coverage in each month. Ethics We did not collect nominal information or individual identifiers. We obtained the data through routine influenza surveillance, Essential Program on Immunizations, and existing health information systems. The analysis used aggregate data only. The project was submitted to the PAHO Ethical Review Committee and deemed exempt as it did not constitute research with human subjects. 

The study included young children and older adults in Chile and Paraguay during the influenza seasons from 2013 to 2018. In Chile, the target populations for the influenza vaccine include children aged 6–23 months and adults aged 65 years and older. In Paraguay, the target populations for the vaccine include children aged 6–23 months and adults aged 60 years and older. Guyana does not have a national influenza immunization program with defined target populations, nor is the influenza vaccine currently available in the private sector. For our estimation, we included the population estimates for children under 5 years old and adults aged 65 years and older during an average year, 2022. 

To estimate the impact of influenza vaccination, we used a static compartmental model adapted from Tokars et al , as previously described , with parameterized monthly estimates of influenza hospitalizations, vaccination coverage, and effectiveness of influenza vaccine. In countries like Chile and Paraguay, which have influenza immunization programs, the model compares influenza illness estimates under an observed vaccination scenario with modeled estimates of illness that would have occurred in the hypothetical absence of a vaccination campaign. In countries like Guyana, which do not yet have an influenza immunization program, the model compares influenza illness estimates with modeled estimates of illness that would have occurred in the hypothetical presence of a vaccination campaign. Additionally, we used the model to assess how increasing vaccine coverage and utilizing different vaccine deployment strategies would impact averted illness. 

Target Population The size of the target population was obtained from the National Institutes of Statistics (Instituto Nacional de Estadística) of Chile and Paraguay . We obtained the target population size for Guyana from the Department of Economic and Social Affairs, United Nations . Estimated Monthly Hospitalizations In Chile and Paraguay, to estimate monthly influenza-associated hospitalizations, we used hospital discharges for which the leading cause of admission was a respiratory system disease diagnosis corresponding to International Classification of Diseases-Tenth Revision (ICD-10) codes J00–J99, by age group. We used the percent positivity for influenza virus obtained from national virologic surveillance by dividing samples positive for any influenza virus by the total number of samples tested. We determined the month- and age-stratified percentage of samples testing positive for the influenza virus by dividing the number of positive samples by the total number of samples analyzed in the same month. For Guyana, which implemented influenza surveillance in 2023, we used influenza-associated hospitalization estimates previously obtained by Palekar et al  available for children younger than 5 years and adults 65 years and older. The total number of influenza hospitalizations were extrapolated from the incidence estimates using the country's total population as of 2022 (808 734 inhabitants, of which 78 980 were children under 5 years and 50 764 were adults aged 65 years and older). In the absence of Guyana's influenza case distribution, which was unavailable for the study period, we obtained the average monthly influenza distribution from 2010 to 2022 using influenza viral circulation distribution from neighboring countries—Suriname and French Guiana—available via FluNet . We used multipliers derived from a Peru study  for hospitalized to nonhospitalized influenza illnesses and the proportion of influenza-associated illnesses that were medically attended to transform influenza-associated hospitalizations into nonhospitalized illnesses (defined as mild to moderate symptomatic influenza illness that may be self-limiting or require outpatient/ambulatory medical care, but not hospitalization) and medically attended illnesses (defined as influenza illnesses requiring medical treatment, including hospitalization) for each age group. Vaccine Coverage and Vaccine Effectiveness The number of people vaccinated against influenza in Chile and Paraguay for each target population per season and month from 2013 to 2018 was collected from administrative influenza vaccination data, electronic records, or coverage surveys. We utilized unpublished data from the REVELAC-i regional influenza vaccine effectiveness estimates, which were calculated using a test-negative design in hospitalized young children (aged 6–24 months) and older adults (aged ≥60 years) in Argentina, Brazil, Chile, Colombia, Paraguay, and Uruguay. For Guyana, we specified vaccine coverage as 30% of the target population. We obtained vaccine effectiveness from a systematic review and meta-analysis published in 2021 for children under 5 years old  and adults aged 65 years and older during the 2017 influenza season . Given year-round circulation of influenza in Guyana, we considered the availability of vaccines for the Northern Hemisphere and the Southern Hemisphere. In the base scenario, the campaign reached 30% coverage over a 4-month campaign (5% coverage in month 1, 10% in month 2, 10% in month 3, 5% in month 4) starting in October (Northern Hemisphere formulation) or in March (Southern Hemisphere formulation). 

The size of the target population was obtained from the National Institutes of Statistics (Instituto Nacional de Estadística) of Chile and Paraguay . We obtained the target population size for Guyana from the Department of Economic and Social Affairs, United Nations . 

In Chile and Paraguay, to estimate monthly influenza-associated hospitalizations, we used hospital discharges for which the leading cause of admission was a respiratory system disease diagnosis corresponding to International Classification of Diseases-Tenth Revision (ICD-10) codes J00–J99, by age group. We used the percent positivity for influenza virus obtained from national virologic surveillance by dividing samples positive for any influenza virus by the total number of samples tested. We determined the month- and age-stratified percentage of samples testing positive for the influenza virus by dividing the number of positive samples by the total number of samples analyzed in the same month. For Guyana, which implemented influenza surveillance in 2023, we used influenza-associated hospitalization estimates previously obtained by Palekar et al  available for children younger than 5 years and adults 65 years and older. The total number of influenza hospitalizations were extrapolated from the incidence estimates using the country's total population as of 2022 (808 734 inhabitants, of which 78 980 were children under 5 years and 50 764 were adults aged 65 years and older). In the absence of Guyana's influenza case distribution, which was unavailable for the study period, we obtained the average monthly influenza distribution from 2010 to 2022 using influenza viral circulation distribution from neighboring countries—Suriname and French Guiana—available via FluNet . We used multipliers derived from a Peru study  for hospitalized to nonhospitalized influenza illnesses and the proportion of influenza-associated illnesses that were medically attended to transform influenza-associated hospitalizations into nonhospitalized illnesses (defined as mild to moderate symptomatic influenza illness that may be self-limiting or require outpatient/ambulatory medical care, but not hospitalization) and medically attended illnesses (defined as influenza illnesses requiring medical treatment, including hospitalization) for each age group. 

The number of people vaccinated against influenza in Chile and Paraguay for each target population per season and month from 2013 to 2018 was collected from administrative influenza vaccination data, electronic records, or coverage surveys. We utilized unpublished data from the REVELAC-i regional influenza vaccine effectiveness estimates, which were calculated using a test-negative design in hospitalized young children (aged 6–24 months) and older adults (aged ≥60 years) in Argentina, Brazil, Chile, Colombia, Paraguay, and Uruguay. For Guyana, we specified vaccine coverage as 30% of the target population. We obtained vaccine effectiveness from a systematic review and meta-analysis published in 2021 for children under 5 years old  and adults aged 65 years and older during the 2017 influenza season . Given year-round circulation of influenza in Guyana, we considered the availability of vaccines for the Northern Hemisphere and the Southern Hemisphere. In the base scenario, the campaign reached 30% coverage over a 4-month campaign (5% coverage in month 1, 10% in month 2, 10% in month 3, 5% in month 4) starting in October (Northern Hemisphere formulation) or in March (Southern Hemisphere formulation). 

We used an Excel-based tool developed by PAHO, the World Health Organization, and the US Centers for Disease Control and Prevention (CDC) (PAHO internal document) to run the model, obtain the averted illness estimates, and analyze varying coverage and vaccine deployment scenarios. We calculated confidence intervals using R software through a Monte Carlo simulation of 5000 iterations. If the lower limit of the confidence intervals for vaccine effectiveness was negative, the limit was set to zero . The analytic methods have been previously described . Briefly, in countries with vaccination programs (ie, Chile and Paraguay), the model calculates the monthly incidence of influenza-associated cases by dividing the events observed each month by the population susceptible to that event in the previous month. The monthly susceptible population is estimated as the total population of the target group minus the population that developed influenza and the population effectively vaccinated that month. For the hypothetical scenario without the vaccine, the monthly incidence of influenza-associated cases is calculated, and the susceptible population is estimated as the total population minus only the population that developed influenza, month by month. For Guyana the number of influenza-associated hospitalizations that could have been prevented through vaccination was estimated as the difference between the observed number of hospitalizations in the absence of vaccination and the expected number of influenza-associated hospitalizations in the presence of vaccination. We present the results as the number of events averted by vaccination (ie, the number of nonhospitalized influenza illnesses, medically attended influenza illnesses, and influenza-associated hospitalizations) and as the prevented fraction of illnesses, estimated as the percentage of the illnesses averted among illnesses that would have occurred in the absence of vaccination. Additional Vaccine Deployment Scenarios To show the average annual effect of vaccination campaigns from 2013 to 2018, we calculated the vaccine's effectiveness for that period and monthly averages of hospitalizations and vaccinations. The median population for that period was also taken into consideration. In addition to the base model, we assessed the effect of increased coverage and different vaccine deployment strategies on the burden of disease averted. The analysis of increased coverage included 40%, 60%, 70%, 75%, 80%, and 90% vaccine coverage. The analysis of campaign deployment scenarios included 3 strategies: in strategy 1, the observed coverage would be achieved in 3 months with the start of the campaign in March (70%, 20%, and 10% of observed coverage in the first, second, and third month, respectively); in strategy 2, the observed coverage would be achieved in 3 months with the start in February (70%, 20%, 10% of observed coverage); and in strategy 3, the observed coverage would be achieved in 2 months with the start in February (80%, 20% of observed coverage). For Guyana, the baseline scenario used the Northern Hemisphere vaccine and the campaign reached 30% coverage over a 4-month campaign starting in October (5%, 10%, 10%, 5%). The alternative scenarios increased the total coverage to 40%, 50%, 60%, and 70%. We defined 4 alternative deployment strategies. In strategies 1 to 3, the campaign would last 3 months, reaching 50%, 30%, and 20% of the coverage in each consecutive month, but the beginning of the campaign was delayed in the second (November) and third strategies (December). In the fourth strategy, the campaign begins in October, but lasts 10 months, with the same monthly coverage in each month. 

To show the average annual effect of vaccination campaigns from 2013 to 2018, we calculated the vaccine's effectiveness for that period and monthly averages of hospitalizations and vaccinations. The median population for that period was also taken into consideration. In addition to the base model, we assessed the effect of increased coverage and different vaccine deployment strategies on the burden of disease averted. The analysis of increased coverage included 40%, 60%, 70%, 75%, 80%, and 90% vaccine coverage. The analysis of campaign deployment scenarios included 3 strategies: in strategy 1, the observed coverage would be achieved in 3 months with the start of the campaign in March (70%, 20%, and 10% of observed coverage in the first, second, and third month, respectively); in strategy 2, the observed coverage would be achieved in 3 months with the start in February (70%, 20%, 10% of observed coverage); and in strategy 3, the observed coverage would be achieved in 2 months with the start in February (80%, 20% of observed coverage). For Guyana, the baseline scenario used the Northern Hemisphere vaccine and the campaign reached 30% coverage over a 4-month campaign starting in October (5%, 10%, 10%, 5%). The alternative scenarios increased the total coverage to 40%, 50%, 60%, and 70%. We defined 4 alternative deployment strategies. In strategies 1 to 3, the campaign would last 3 months, reaching 50%, 30%, and 20% of the coverage in each consecutive month, but the beginning of the campaign was delayed in the second (November) and third strategies (December). In the fourth strategy, the campaign begins in October, but lasts 10 months, with the same monthly coverage in each month. 

We did not collect nominal information or individual identifiers. We obtained the data through routine influenza surveillance, Essential Program on Immunizations, and existing health information systems. The analysis used aggregate data only. The project was submitted to the PAHO Ethical Review Committee and deemed exempt as it did not constitute research with human subjects. 

From 2013 to 2018, Chile had an average annual population of 368 097 children aged 6 to 23 months, with 43 128 influenza cases and 967 hospitalizations. The Southern Hemisphere vaccine used had a median effectiveness of 44% (95% confidence interval [CI], 28–57) and a vaccination coverage of 67.8%. During the same period, 1 956 623 adults aged 65 and older experienced 325 738 influenza cases and 5429 hospitalizations. Their median vaccine effectiveness was 37%, with a coverage of 59.4%. Vaccination campaigns for both age groups began in March ( ). Paraguay's median population of children aged 6 to 23 months was 211 329, with 13 730 influenza cases and 308 hospitalizations. Vaccine coverage was 28%. For adults aged 60 and older, the population was 608 850, with 33 985 cases, 566 hospitalizations, and a coverage of 36.4%. Vaccination typically started in April, except in 2016 and 2018, when it began in May ( ). Between 2022 and 2023, Guyana had a median population of 78 980 children under 5 years, reporting 10 136 influenza cases and 69 hospitalizations. Among adults aged 65 years and older, with a median population of 50 764, there were 5520 cases and 92 hospitalizations. Hypothetically, using the Northern Hemisphere vaccine, we assumed 30% coverage for both groups, starting in October, with effectiveness at 53% for children and 37% for older adults ( ). Vaccine-Averted Influenza Illness Among Children Aged 6–23 Months in Chile and Paraguay During 2013 and 2018 In Chile, influenza vaccination averted a mean of 14 617 nonhospitalized influenza illnesses, 9426 medically attended illnesses, and 328 hospitalizations per year among the 368 097 children aged 6–23 months ( ). In Paraguay, influenza vaccination averted a mean of 1115 nonhospitalized influenza illnesses, 719 medically attended illnesses, and 25 hospitalizations per year among the 211 329 children aged 6–23 months. The averted influenza illnesses varied substantially by year; the greatest prevented fraction was estimated in 2018 (Chile 35.6%; 95% CI, 27.3%–42.1% and Paraguay 11.8%; 95% CI, 9.0%–13.9%), and the lowest prevented fraction was observed in 2014 (Chile 7.2%; 95% CI, 0.0%–23.4% and Paraguay 2.7%; 95% CI, 0.0%–8.9%). Burden of Influenza Disease Averted in Older Adults in Chile and Paraguay In Chile, influenza vaccination averted a mean of 83 429 nonhospitalized influenza illnesses, 37 079 medically attended illnesses, and 1390 hospitalizations per year among 1 956 623 people 65 years and older ( ). In Paraguay, influenza vaccination averted a mean of 3932 nonhospitalized illnesses, 1748 medically attended illnesses, and 66 hospitalizations per year among 608 850 people 60 years and older. The averted influenza illnesses varied substantially by year; the greatest prevented fraction was observed in 2014 in Chile (27.9%; 95% CI, 20.5%–33.6%) and in 2013 in Paraguay (17.5%; 95% CI, 13.2%–21.0%) and the lowest prevented fraction was observed in 2017 in Chile (9.8%; 95% CI, 0.0%–17.8%) and in 2015 in Paraguay (5.7%; 95% CI, 0.8%–9.6%). Simulation of Influenza Averted Burden in Guyana In 2022, the total population in Guyana was 808 734, of whom 78 980 were children younger than 5 years and 50 764 were adults aged 65 years and older ( ). Averted influenza illnesses from a hypothetical vaccination campaign in Guyana are shown in . Vaccination in advance of the Northern Hemisphere influenza season (ie, October–January) would have averted more influenza illnesses than vaccinating in advance of the Southern Hemisphere season (ie, March–June); in children younger than 5 years, vaccination before the Northern Hemisphere season would have prevented an estimated 1496 nonhospitalized illnesses, 971 medically attended illnesses, and 10 hospitalizations, with a prevented fraction of 14.8% ( ). In older adults (aged ≥65 years), vaccination before the Northern Hemisphere season would have prevented 568 nonhospitalized illnesses, 257 medically attended illnesses, and 10 hospitalizations, with a prevented fraction of 10.3%. Additional Vaccine Scenarios The number of averted illnesses increased under all modeled scenarios of increased vaccination coverage in Chile and Paraguay, both for children and older adults ( and ). In Chile, all 3 modeled vaccine deployment strategies with earlier start dates and more concentrated campaigns increased the number of vaccine-averted nonhospitalized illnesses, medically attended illnesses, and hospitalizations, although strategies 2 (advancing the start of the campaign by 1 month and concentrating deployment to 3 months) and 3 (advancing the start of the campaign by 1 month and concentrating deployment to 2 months) outperformed the baseline strategy by a few thousand averted illnesses (ie, percentage change from baseline: +16.1% for strategy 2 and +16.4% for strategy 3 among children; +4.4% for strategy 2 and +4.7% for strategy 3 among older adults). Similarly, in Paraguay, all 3 modeled strategies also increased averted illnesses among children and adults; strategy 3 resulted in the most averted nonhospitalized illnesses (27 032), medically attended illnesses (12 014), and hospitalizations (451) in older adults ( ). In an average influenza season in Guyana, strategy 1 (concentrating deployment to 3 months) would achieve the maximum potential of the campaign, but the impact of the baseline strategy (deployment across 4 months) and strategy 2 (concentrating deployment to 3 months and delaying the campaign 1 month) would be minimally different. Strategy 1 and a 70% coverage of the influenza vaccination campaign could avoid 25 hospitalizations and 3610 nonhospitalized illnesses in children younger than 5 years and 23 hospitalizations and 1371 nonhospitalized illnesses in adults older than 65 ( ). 

In Chile, influenza vaccination averted a mean of 14 617 nonhospitalized influenza illnesses, 9426 medically attended illnesses, and 328 hospitalizations per year among the 368 097 children aged 6–23 months ( ). In Paraguay, influenza vaccination averted a mean of 1115 nonhospitalized influenza illnesses, 719 medically attended illnesses, and 25 hospitalizations per year among the 211 329 children aged 6–23 months. The averted influenza illnesses varied substantially by year; the greatest prevented fraction was estimated in 2018 (Chile 35.6%; 95% CI, 27.3%–42.1% and Paraguay 11.8%; 95% CI, 9.0%–13.9%), and the lowest prevented fraction was observed in 2014 (Chile 7.2%; 95% CI, 0.0%–23.4% and Paraguay 2.7%; 95% CI, 0.0%–8.9%). 

In Chile, influenza vaccination averted a mean of 83 429 nonhospitalized influenza illnesses, 37 079 medically attended illnesses, and 1390 hospitalizations per year among 1 956 623 people 65 years and older ( ). In Paraguay, influenza vaccination averted a mean of 3932 nonhospitalized illnesses, 1748 medically attended illnesses, and 66 hospitalizations per year among 608 850 people 60 years and older. The averted influenza illnesses varied substantially by year; the greatest prevented fraction was observed in 2014 in Chile (27.9%; 95% CI, 20.5%–33.6%) and in 2013 in Paraguay (17.5%; 95% CI, 13.2%–21.0%) and the lowest prevented fraction was observed in 2017 in Chile (9.8%; 95% CI, 0.0%–17.8%) and in 2015 in Paraguay (5.7%; 95% CI, 0.8%–9.6%). 

In 2022, the total population in Guyana was 808 734, of whom 78 980 were children younger than 5 years and 50 764 were adults aged 65 years and older ( ). Averted influenza illnesses from a hypothetical vaccination campaign in Guyana are shown in . Vaccination in advance of the Northern Hemisphere influenza season (ie, October–January) would have averted more influenza illnesses than vaccinating in advance of the Southern Hemisphere season (ie, March–June); in children younger than 5 years, vaccination before the Northern Hemisphere season would have prevented an estimated 1496 nonhospitalized illnesses, 971 medically attended illnesses, and 10 hospitalizations, with a prevented fraction of 14.8% ( ). In older adults (aged ≥65 years), vaccination before the Northern Hemisphere season would have prevented 568 nonhospitalized illnesses, 257 medically attended illnesses, and 10 hospitalizations, with a prevented fraction of 10.3%. 

The number of averted illnesses increased under all modeled scenarios of increased vaccination coverage in Chile and Paraguay, both for children and older adults ( and ). In Chile, all 3 modeled vaccine deployment strategies with earlier start dates and more concentrated campaigns increased the number of vaccine-averted nonhospitalized illnesses, medically attended illnesses, and hospitalizations, although strategies 2 (advancing the start of the campaign by 1 month and concentrating deployment to 3 months) and 3 (advancing the start of the campaign by 1 month and concentrating deployment to 2 months) outperformed the baseline strategy by a few thousand averted illnesses (ie, percentage change from baseline: +16.1% for strategy 2 and +16.4% for strategy 3 among children; +4.4% for strategy 2 and +4.7% for strategy 3 among older adults). Similarly, in Paraguay, all 3 modeled strategies also increased averted illnesses among children and adults; strategy 3 resulted in the most averted nonhospitalized illnesses (27 032), medically attended illnesses (12 014), and hospitalizations (451) in older adults ( ). In an average influenza season in Guyana, strategy 1 (concentrating deployment to 3 months) would achieve the maximum potential of the campaign, but the impact of the baseline strategy (deployment across 4 months) and strategy 2 (concentrating deployment to 3 months and delaying the campaign 1 month) would be minimally different. Strategy 1 and a 70% coverage of the influenza vaccination campaign could avoid 25 hospitalizations and 3610 nonhospitalized illnesses in children younger than 5 years and 23 hospitalizations and 1371 nonhospitalized illnesses in adults older than 65 ( ). 

We estimated that influenza vaccination campaigns in Chile averted more than 25% of the mean annual disease burden in young children and more than 20% among older adults. In Paraguay, influenza vaccination reduced nearly 10% of the influenza burden among young children and over 10% among older adults. For Guyana, a hypothetical influenza vaccination campaign with 30% coverage could have prevented nearly 15% of the disease burden in children and 10% in adults aged 65 and older in an average year. Differences in averted influenza illnesses observed by year in Chile and Paraguay were due largely to annual variations in influenza vaccine effectiveness, coverage achieved, timeliness of the start of the campaign, and speed at which final coverage was achieved. In Chile, we found that increasing vaccine coverage had the greatest impact on averted illness; by comparison, achieving coverage in the first 3 months of the campaign and starting the campaign earlier would not have substantially impacted the reduction in disease burden. In Paraguay, vaccine coverage and campaign timing would substantially impact the vaccine-averted disease burden among older adults. An earlier start to the campaign to achieve coverage prior to peak influenza circulation would have prevented an additional 2% of the disease burden. Such an impact was not observed among children, as the complete vaccination scheme in a large proportion of children requires 2 influenza vaccine doses. In both countries, the vaccine-averted disease burden is concentrated in the months with the highest health care demand during the influenza season, reducing the upsurge in health systems. In countries like Guyana, where influenza surveillance was recently implemented and the influenza vaccine has not yet been introduced, modeling the disease burden and the potential impact of a vaccination campaign might aid policymakers and the public to understand the value of influenza vaccination. Our analysis suggests that introducing the influenza vaccine could reduce the disease burden, especially in children under 5 years. Vaccinating in advance of the Northern Hemisphere season would likely have a greater impact than vaccinating in advance of the Southern Hemisphere season, considering the timing of the influenza season in Guyana. Early vaccination with high, concentrated coverage is more effective than vaccinating later in the year, although improving influenza surveillance is recommended to verify these results. With a population of 800 000, Guyana has a low burden of influenza disease, resulting in a relatively low vaccine impact in absolute numbers; however, because the influenza surveillance system is in its early stages, the burden may increase with more years of data, which will lead to an increase in the vaccine impact. Our analysis highlights the benefits of seasonal vaccination in preventing severe cases in Guyana, supporting the introduction of the influenza vaccine in high-risk groups. In addition to children and older adults, the WHO also recommends influenza vaccination for health professionals, pregnant women, and people with comorbidities; exploring the value of vaccinating these other vaccine target groups in Guyana may be considered as well . Other factors to consider prior to influenza vaccine introduction include cost of a government-subsidized vaccination program, cost-effectiveness of vaccination, acceptability of the vaccine by the population, and capacity of the health system to deliver the vaccines . The results of influenza vaccine impact analyses have several potential uses, one of them being to facilitate the delivery of information to the public regarding the value of vaccinating communities, information that may be easier for the public to understand than vaccine effectiveness. For example, Paraguay used the results of this analysis for a communication strategy aimed at increasing influenza vaccination coverage by raising awareness among the target population ( https://www.facebook.com/share/r/Dk5UCvMzZH1u7vke/?mibextid=0VwfS7 ). Moreover, the burden of influenza-associated disease prevented by vaccination is necessary for economic and cost-effectiveness analyses of vaccines. This analysis has several limitations. First, we estimated burden of influenza disease based on respiratory disease symptoms and not the wider spectrum of illnesses and complications attributed to influenza. This may result in undercounting more than half of the total influenza disease burden in some groups, such as children. Therefore, estimates of vaccine-averted influenza illnesses are likely underestimated. Second, these results are based on regional vaccine effectiveness data obtained through the REVELAC-i network, which includes Chile and Paraguay, but may still vary locally depending on the circulation of different influenza virus types and subtypes. Third, effectiveness estimates show the effectiveness in preventing hospitalizations (SARI) but not outpatient cases or cases in the community. Therefore, averted respiratory influenza illnesses could be overestimated. Fourth, vaccine effectiveness was assumed to remain constant throughout the season, with protection lasting until the beginning of the next season, regardless of when it was administered. Fifth, the potential indirect effects of the vaccination program or herd immunity were not considered, as integrating these factors into existing evidence at the regional level has many challenges . Sixth, to estimate the burden of the milder disease, we used multipliers based on a cohort in Peru. Due to potential societal and cultural differences in health care access, estimates may not accurately reflect Chile, Guyana, and Paraguay . Finally, to model the potential averted burden scenarios in Guyana, model inputs were based on secondary sources of information and assumptions that may not accurately represent the reality in the country. For example, we assumed that influenza incidence and epidemic curves in Guyana were similar to those in Suriname and French Guyana, neighboring Caribbean countries, and assumed the vaccine effectiveness was the same for all seasons and all disease severity levels. Additionally, the population size for averted illness among children includes all children aged <5 years, including children 0–6 months who are too young for influenza vaccination; therefore, the estimate of averted illness among the target population (children 6–59 months) is an overestimate. 

Influenza vaccination campaigns were estimated to reduce influenza-associated disease burden in Chile and Paraguay during 2013–2018 by 10%–25%, and influenza vaccination could have similar impacts if introduced in Guyana. In addition to increasing vaccine coverage, the timing of influenza vaccine campaigns is crucial to their impact, with the greatest benefits observed when campaigns start as soon as the vaccine is available and high coverage is achieved within 2 to 3 months of campaign start. Estimates of vaccine-averted illnesses can be used to inform the public about the value of influenza vaccination for the community, to motivate providers to offer more influenza vaccination to those eligible, as inputs for economic and cost-effectiveness analyses of vaccines, and to help policy makers determine the optimal timing and deployment of vaccine campaigns. In conclusion, while influenza vaccination campaigns effectively reduce the burden of influenza-associated disease, ongoing surveillance and long-term evaluations are crucial for accurately assessing their effectiveness and impact. 

are available at The Journal of Infectious Diseases online ( http://jid.oxfordjournals.org/ ). consist of data provided by the author that are published to benefit the reader. The posted materials are not copyedited. The contents of all are the sole responsibility of the authors. Questions or messages regarding errors should be addressed to the author. 

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