Flu Scan for Mar 08, 2018

Vaccine effect after repeat vaccines
;
4-strain flu vaccine in youngest kids
;
H5N1 avian flu in India

Schoolchildren study finds lower protection after repeated flu vaccination

Editor's Note: This scan was updated on Mar 9 to better reflect the limitations of the study, especially statistically insignificant data. Many thanks to New Zealand–based risk and policy adviser Ron Law for his astute observations after this item was published.

A study of the impact of prior flu vaccination on effectiveness in the current season in Japanese schoolchildren found a significant association between reduced vaccine effectiveness (VE) against medically attended flu and repeated vaccination, but the study findings were limited because of statistically insignificant findings in study subgroups, use of rapid diagnostic tests (RDTs), and other factors.

The findings come as experts in the United States and other countries are trying to untangle the reasons for a drop in effectiveness against the H3N2 strain over the past few seasons, some of which is likely related to egg-mediated mutations in the vaccine production process. However, other factors may play a role. Japanese researchers reported their findings today in Clinical Infectious Diseases.

Their study took place in children ages 9 to 18 who were seen for flulike illness at a community hospital on a remote island in Japan over the 2011-12 through 2013-14 flu seasons. Vaccine coverage on the island is high, past vaccination status is recorded in a vaccine registry, and information from clinic visits and rapid diagnostic tests results are part of the electronic medical record.

Over the three seasons, the researchers analyzed 1,668 flulike illness episodes, of which 421 were confirmed as influenza A and 358 were confirmed as influenza B. They found a dose-dependent attenuation by earlier vaccination against both influenza A and B.

For influenza A, adjusted VE was 96% in those who hadn't been vaccinated in the previous season, with the level falling to 48% in those with 1 earlier dose, 52% in those who got 2 earlier doses, and 21% in kids who received 3 previous doses. For influenza B, the levels were 66% VE in those who hadn't previously been vaccinated, 48% in those who had gotten 1 earlier dose, 34% in those who had 2 prior doses, and -7% in those who had received 3 earlier doses. The investigators also saw a protective effect from natural flu infection in previous seasons.

However, VE reached statistical significance in only one of the eight subgroups of children: against influenza A in children who had received 2 previous doses. For all the other subsets, the 95% confidence interval dipped into negative numbers, and all confidence intervals were wide, reflecting weaker findings.

The team wrote that their report is the first to show a statistically significant association between the attenuated effects of flu VE and prior vaccine doses. They noted that the findings might not be generalizable to other age-groups, given that schoolchildren typically have high immune responses to vaccines, and added that more studies are needed to confirm the findings. They also detail several shortcomings of their research, including an observational design and the use of RDTs, which are not as sensitive as polymerase chain reaction, the gold standard for influenza.
Mar 8 Clin Infect Dis abstract

 

Study: 4-strain flu vaccine cuts flu, other health burdens in youngest kids

A phase 3 trial of GlaxoSmithKline's (GSK's) quadrivalent (four-strain) flu vaccine (Fluarix Tetra) in children ages 6 to 35 months not only found high efficacy against moderate-to-severe flu, but also a reduction in health utilization indicators, such as antibiotic use, clinic visits, and parental work absences.

The study, which spanned 13 countries in Europe, Central America, and Asia, was conducted during the 2011-12 and 2012-13 flu seasons in the Northern Hemisphere and 2012 to 2014 flu seasons in the Southern Hemisphere. An international research team reported its findings this week in The Lancet Child & Adolescent Health.

In January, the United States Food and Drug Administration (FDA) approved an expanded indication for Fluarix Tetra, allowing it to be used for children ages 6 to 35 months.

The study enrolled 12,018 children, 6,006 who had received the quadrivalent vaccine and 6,012 who had received vaccines against other diseases. There were 356 lab-confirmed flu cases (6%) in the flu vaccine group and 693 (12%) confirmed flu cases in the control group.

Against moderate-to-severe flu, vaccine efficacy was 63.2%, and against flu of any severity, efficacy was 49.8%.

Thomas Breuer, MD, MSc, GSK's chief medical officer, said in a press release from the company that the study is the first to evaluate vaccine efficacy for a quadrivalent vaccine in young children. He noted that young kids are in the high-risk group for flu complications and play a major role in community spread. "It adds to the growing body of evidence to support universal vaccination including all children from 6 months of age to help prevent influenza in this age group, as well as the spread of influenza across the community," Breuer said.

Among the other findings, the team determined that the vaccine was associated with a 50% reduction in antibiotic, 47% cut in clinic visits, 79% less emergency department visits, 54% lower rate of parent work absence, and 55% lower missed childcare days. The safety profiles of the flu vaccine and control vaccines were similar.
Mar 5 Lancet Child Adolesc Health abstract
Mar 6 GSK press release

 

H5N1 avian flu outbreak strikes poultry in India

India's agriculture ministry has reported a highly pathogenic H5N1 avian influenza outbreak in backyard poultry in Orissa state in the eastern part of the country, according to a notification yesterday from the World Organization for Animal Health (OIE).

The event began on Feb 11, and all 1,823 birds were culled as part of the response, which also includes increased surveillance, movement control, and disinfection. So far, investigators haven't found the source of the outbreak.

India's last H5N1 in poultry occurred in June 2017, but last week the virus was detected in house crows in the same district of Orissa state.
Mar 7 OIE report in H5N1 in India

Editor's Note: This scan was updated on Mar 9 to better reflect the limitations of the study, especially statistically insignificant data. Many thanks to New Zealand–based risk and policy adviser Ron Law for his astute observations after this item was published.

A study of the impact of prior flu vaccination on effectiveness in the current season in Japanese schoolchildren found a significant association between reduced vaccine effectiveness (VE) against medically attended flu and repeated vaccination, but the study findings were limited because of statistically insignificant findings in study subgroups, use of rapid diagnostic tests (RDTs), and other factors.

The findings come as experts in the United States and other countries are trying to untangle the reasons for a drop in effectiveness against the H3N2 strain over the past few seasons, some of which is likely related to egg-mediated mutations in the vaccine production process. However, other factors may play a role, such as reduced immune response correlated to earlier exposure to the vaccine or the disease. Japanese researchers reported their findings today in Clinical Infectious Diseases.

Their study took place in children ages 9 to 18 who were seen for flulike illness at a community hospital on a remote island in Japan over the 2011-12 through 2013-14 flu seasons. Vaccine coverage on the island is high, past vaccination status is recorded in a vaccine registry, and information from clinic visits and rapid diagnostic tests results are part of the electronic medical record.

Over the three seasons, the researchers analyzed 1,668 flulike illness episodes, of which 421 were confirmed as influenza A and 358 were confirmed as influenza B. They found a dose-dependent attenuation by earlier vaccination against both influenza A and B.

For influenza A, adjusted VE was 96% in those who hadn't been vaccinated in the previous season, with the level falling to 48% in those with 1 earlier dose, 52% in those who got 2 earlier doses, and 21% in kids who received 3 previous doses. For influenza B, the levels were 66% VE in those who hadn't previously been vaccinated, 48% in those who had gotten 1 earlier dose, 34% in those who had 2 prior doses, and -7% in those who had received 3 earlier doses. The investigators also saw a protective effect from natural flu infection in previous seasons.

However, VE reached statistical significance in only one of the eight subgroups of children: against influenza A in children who had received 2 previous doses. For all the other subsets, the 95% confidence interval dipped into negative numbers, and all confidence intervals were wide, reflecting weaker findings.

The team wrote that their report is the first to show a statistically significant association between the attenuated effects of flu VE and prior vaccine doses. They noted that the findings might not be generalizable to other age-groups, given that schoolchildren typically have high immune responses to vaccines, and added that more studies are needed to confirm the findings. They also detail several shortcomings of their research, including an observational design and the use of RDTs, which are not as sensitive as polymerase chain reaction, the gold standard for influenza.
Mar 8 Clin Infect Dis abstract

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