In the Journals

Infant flu-associated hospitalizations may be higher than current estimates

Mark G. Thompson, PhD
Mark G. Thompson

The incidence of laboratory-confirmed influenza-associated hospital admissions among infants may be more than 2 times higher than current estimates, according to findings from four low- and middle-income countries published in The Lancet Child & Adolescent Health.

“There are debates under way right now in low- and middle-income countries about whether to invest in maternal influenza vaccination programs that could benefit infants aged less than 6 months old, and whether to invest in direct vaccination of infants aged 6 to 11 months,” Mark G. Thompson, PhD, from the CDC’s Influenza Division, told Infectious Diseases in Children. “For a lot of these countries, the economic math is very tight and there are many competing priorities. Most face the burden of severe disease that requires hospitalization as a major factor in decision-making, so doubling the potential burden and thus doubling the potential preventive value of influenza vaccines could have a big impact on policy decisions.”

To assess the extent to which current respiratory surveillance platforms may underestimate the frequency of severe influenza disease among infants, Thompson and colleagues conducted a prospective observational study at four hospitals in Albania, Jordan, Nicaragua and the Philippines between June 2015 and April 2017. They used real-time RT-PCR (rRT-PCR) and serology to assess the frequency of influenza virus infections.

They enrolled 3,634 acutely ill infants, including 1,943 who were enrolled during influenza seasons and had complete acute-convalescent pairs. Of these 1,943 infants, 94 (5%) tested positive for influenza by both rRT-PCR and serology, 58 (3%) tested positive by rRT-PCR only and 102 (5%) tested positive by serology only.

The researchers observed seroconversion to at least one of the influenza A or B viruses among 196 (77%) of 254 influenza-positive infants, of whom 84 (33%) only had nonrespiratory clinical discharge diagnoses. These included sepsis, febrile seizures, dehydration or other non-respiratory viral illness, the researchers wrote.

They concluded that a focus on respiratory diagnoses and rRT-PCR-confirmed influenza fails to detect influenza-associated hospital admissions among infants by a factor of 2.6 (95% CI, 2-3.6). The findings remained unchanged when syndromic severe acute respiratory infection criteria were applied instead of critical diagnosis, they wrote.

According to Thompson, these findings have both clinical and policy implications in high-income countries like the United States.

“For clinicians, our findings are a reminder that atypical presentations of influenza among infants are common,” he said. “About one in three of the infants with influenza confirmed by serologic testing in our study were discharged with only nonrespiratory diagnoses, like febrile seizures or sepsis or a clinical sign like extreme dehydration. Thus, the clinicians did not view them as having a respiratory illness.”

Regarding vaccine policy, Thompson noted that knowing the true burden of influenza among infants may be twice as high as previously thought reinforces the importance of continuing to improve influenza vaccine coverage among pregnant women and infants aged older than 6 months. – by Joe Gramigna

Disclosures: The authors report no relevant financial disclosures.

Mark G. Thompson, PhD
Mark G. Thompson

The incidence of laboratory-confirmed influenza-associated hospital admissions among infants may be more than 2 times higher than current estimates, according to findings from four low- and middle-income countries published in The Lancet Child & Adolescent Health.

“There are debates under way right now in low- and middle-income countries about whether to invest in maternal influenza vaccination programs that could benefit infants aged less than 6 months old, and whether to invest in direct vaccination of infants aged 6 to 11 months,” Mark G. Thompson, PhD, from the CDC’s Influenza Division, told Infectious Diseases in Children. “For a lot of these countries, the economic math is very tight and there are many competing priorities. Most face the burden of severe disease that requires hospitalization as a major factor in decision-making, so doubling the potential burden and thus doubling the potential preventive value of influenza vaccines could have a big impact on policy decisions.”

To assess the extent to which current respiratory surveillance platforms may underestimate the frequency of severe influenza disease among infants, Thompson and colleagues conducted a prospective observational study at four hospitals in Albania, Jordan, Nicaragua and the Philippines between June 2015 and April 2017. They used real-time RT-PCR (rRT-PCR) and serology to assess the frequency of influenza virus infections.

They enrolled 3,634 acutely ill infants, including 1,943 who were enrolled during influenza seasons and had complete acute-convalescent pairs. Of these 1,943 infants, 94 (5%) tested positive for influenza by both rRT-PCR and serology, 58 (3%) tested positive by rRT-PCR only and 102 (5%) tested positive by serology only.

The researchers observed seroconversion to at least one of the influenza A or B viruses among 196 (77%) of 254 influenza-positive infants, of whom 84 (33%) only had nonrespiratory clinical discharge diagnoses. These included sepsis, febrile seizures, dehydration or other non-respiratory viral illness, the researchers wrote.

They concluded that a focus on respiratory diagnoses and rRT-PCR-confirmed influenza fails to detect influenza-associated hospital admissions among infants by a factor of 2.6 (95% CI, 2-3.6). The findings remained unchanged when syndromic severe acute respiratory infection criteria were applied instead of critical diagnosis, they wrote.

According to Thompson, these findings have both clinical and policy implications in high-income countries like the United States.

“For clinicians, our findings are a reminder that atypical presentations of influenza among infants are common,” he said. “About one in three of the infants with influenza confirmed by serologic testing in our study were discharged with only nonrespiratory diagnoses, like febrile seizures or sepsis or a clinical sign like extreme dehydration. Thus, the clinicians did not view them as having a respiratory illness.”

Regarding vaccine policy, Thompson noted that knowing the true burden of influenza among infants may be twice as high as previously thought reinforces the importance of continuing to improve influenza vaccine coverage among pregnant women and infants aged older than 6 months. – by Joe Gramigna

Disclosures: The authors report no relevant financial disclosures.