Nov 11, 2011 (CIDRAP News) – An international group of researchers estimates that seasonal flu worldwide causes 90 million acute lower respiratory infections a year in young children, with 1 million of the cases severe enough to require hospitalization.
Their work, a systematic meta-analysis of 43 studies and the first global estimate of the seasonal flu burden in this population, focused on children younger than 5. It also linked flu to 28,000 to 111,500 deaths in that age-group across the world each year.
The researchers published their findings today in an early online edition of The Lancet. Last year the same group estimated that respiratory syncytial virus was the most common pathogen responsible for lower respiratory infections in kids.
To arrive at their influenza estimate, they conducted a literature review to identify studies of lab-confirmed flu in children younger than 5 years old that were published between January 1995 and October 2010. Forty-three studies, which covered 8 million children, met their inclusion criteria.
To address information gaps about flu infections and deaths in developing countries, they formed an international study group to supplement the published studies with unpublished data. The group's overall goal was to estimate the flu burden in young children in 2008 globally and for six World Health Organization (WHO) regions.
For 2008, they estimated about 90 million new cases of flu (95% confidence interval [CI]; 49 million to 162 million), along with 20 million (13 million to 32 million) cases of flu-related acute lower respiratory infections and 1 million (1 million to 2 million) severe infections.
The estimates varied by country and region, due to differences in methodology and flu epidemiology. In their analysis of the data, they outlined several factors that could have overestimated or underestimated the true flu incidence. For example, they wrote that some of the studies they included used immunofluorescence to diagnose flu, which can have lower sensitivity and specificity than polymerase chain reaction testing.
Also, the group said it was difficult to form a precise estimate for global flu-related mortality in kids, because evidence is sparse, a factor they say might have since changed if countries improved their data collection in the wake of the 2009 H1N1 pandemic.
Global flu estimates could be used to help guide public health policy and vaccine strategies, especially in developing countries, the investigators concluded. They added that donor agencies can also use the findings to help set funding priorities for new vaccine development and the implementation of other flu-prevention strategies.
In a commentary on the study findings, which appears in the same Lancet issue, Dr Maria Zambon, who directs the Centre for Infections at the UK Health Protection Agency (HPA), wrote that during WHO discussions about seasonal flu vaccine use in global programs, experts agreed that an evidence-based estimate of global flu burden would help guide policy development.
She wrote that the Lancet report "is a big step in the right direction."
The data limitations that the group identified strongly suggest a need to implement routine objective disease measures within national surveillance systems, Zambon wrote.
A notable finding was that most childhood flu morality occurred outside hospital settings, with a 15-fold difference in case-fatality ratios between developed and developing countries, she noted. "Most of the world's children live in the developing world. This finding is confirmation of the high disease burden caused by influenza in the youngest age groups, even if the exact numbers are obscure."
She said evidence-based data are crucial for regions that have few resources and many competing health priorities.
Neal Halsey, MD, director of the Institute for Vaccine Safety and professor in the Bloomberg School of Public Health at Johns Hopkins University, told CIDRAP News that he was aware that a research group was working on the global flu estimate in kids, because some investigators from Johns Hopkins were involved.
The study's findings aren't surprising to people who work with pediatric infectious diseases or influenza, he said, and it's clear that flu is an important health burden in US children. "We knew there had to be a substantial burden in the rest of the world, but we haven't had the data. This is consistent with everything we know about flu," Halsey said.
Influenza is a severe disease on its own and can predispose patients to secondary bacterial pneumonia, which is especially a problem in developing countries, he said. Given that a substantial number of those infections are preventable, the next step will be to determine what role flu immunization could play. He added that flu vaccine is inexpensive and isn't more difficult to administer in developing countries that other types of vaccines.
One difficulty is that the flu vaccine changes every year, so the vaccine must be given annually, Halsey said. "That's the real challenge."
A recent meta-analysis in Lancet Infectious Diseases on flu vaccine efficacy found gaps in evidence in some age-groups, including a lack of randomized controlled trials (RCTs) showing trivalent inactivated vaccine (TIV) protection in 2- to 17-year-olds and people over 65, as well as no RCTs supporting live attenuated influenza vaccine (LAIV) in people ages 8 through 59. Studies showed consistently higher levels of protection for LAIV in kids aged 7 and younger compared with TIV in adults 18 to 65.
Halsey said that even with the current vaccines, greater use of them in young children could reduce a substantial number of severe infections and deaths.
Nair H, Brooks WA, Katz M, et al. Global burden of respiratory infections due to seasonal flu in young children: a systematic review and meta-analysis. Lancet 2011 Nov 11 [Abstract]
Zambon M. Assessment of the burden of influenza in children. (Commentary) Lancet 2011 Nov 11 [Extract]
Oct 25 CIDRAP News story "Strict meta-analysis raises questions about flu vaccine efficacy"