The N E W E N G L A N D J O U R N A L o / M E D I C I N E
Influenza Vaccination o f Pregnant W om en and Protection o f Their Infants to th e e d ito r :
Madhi et al. (Sept. 4 issue)1 de scribe the protection of pregnant women and in fants conferred by the trivalent inactivated influ enza vaccine (IIV3). One of the primary outcomes of the study was the efficacy of IIV3 adminis tered during pregnancy to protect infants against confirmed influenza. The vaccine efficacy was reported to be 48.8% among infants whose mothers did not have human immunodeficiency virus (HIV) infection. This means that although their mothers were immunized, 51.2% of the in fants were not protected. The question arises as to whether the infants who did not gain effective immunity were also those who were immunologically predisposed to severe disease. Hence, what was the severity of the influenza in the un protected vaccinated group as compared with the placebo group? Was there an overrepresentation of influenza infections that were severe enough to require hospitalization in the vaccinated group? If this were the case, then from a clinical per spective, the vaccine would be of limited value. Would the authors please provide data on the number o f confirmed cases of influenza that were severe enough to require hospitalization in both the vaccinated and placebo groups?
lished, acquisition of hemagglutinin antibody transplacentally or through breast-feeding1 or indirectly by preventing influenza infection in mothers and reducing transmission to their in fants may be involved. Although our study was not designed to evaluate the efficacy of the vac cine against influenza with respect to hospital ization, we observed two hospitalizations for confirmed influenza (manifested as lower respi ratory tract illness) among infants o f HlV-uninfected recipients of placebo and none among those born to IIV3 recipients. Hence, there is no evidence that infants of women who had been vaccinated with IIV3 were predisposed to more severe illness. Notably, 92% effectiveness of the vaccine against confirmed influenza leading to hospitalization2 and a 39% reduction in the risk o f clinically diagnosed influenza-like illness leading to hospitalizations3 have previously been observed in infants of women who had been vac cinated with IIV3, as compared with unexposed controls. This suggests that IIV3 vaccination of pregnant women may have greater effectiveness in protecting against severe influenza illness than against mild influenza illness in their in fants.
Ingrid Horner, M.B., B.S., M.P.H.T.M. Ralph Nanan, Dr.Med.Habil. Anthony Liu, M.B., B.S., M.P.H.
Shabir A. Madhi, M.D., Ph.D. Marta C. Nunes, Ph.D. Clare L. Cutland, M.D.
Nepean Hospital Sydney, NSW, Australia
University o f the W itwatersrand Johannesburg, South Africa [email protected]
No potential conflict of interest relevant to this letter was re ported. 1. Madhi SA, Cutland CL, Kuwanda L, et al. Influenza vaccina tion of pregnant women and protection of their infants. N Engl J Med 2014;371:918-31. DOI: 10.1056/NEJMcl412050
th e au th o r s reply: Horner et al. comment on the efficacy of IIV3 vaccination o f pregnant women in protecting infants who are younger than 24 weeks of age. Although the mechanism o f protection in infants remains to be estab
2340
N ENGLJ
M ED 3 7 i;2 4
Since publication of their article, the authors report no fur ther potential conflict of interest. 1. Schlaudecker EP, Steinhoff MC, Omer SB, et al. IgA and neu tralizing antibodies to influenza A virus in human milk: a ran domized trial of antenatal influenza immunization. PLoS One 2013;8(8):e70867. 2. Benowitz I, Esposito DB, Gracey KD, Shapiro ED, Vazquez M. Influenza vaccine given to pregnant women reduces hospital ization due to influenza in their infants. Clin Infect Dis 2010; 51:1355-61. 3. Eick AA, Uyeki TM, Klimov A, et al. Maternal influenza vac cination and effect on influenza virus infection in young in fants. Arch Pediatr Adolesc Med 2011;165:104-11. DOI: 10.1056/N EJMcl412050
N E JM .O R G
D E C E M B E R 11, 2 O I 4
Copyright © Massachusetts Medical Society 2014.
Influenza Vaccination o f Pregnant W om en and Protection o f Their Infants to th e e d ito r :
Madhi et al. (Sept. 4 issue)1 de scribe the protection of pregnant women and in fants conferred by the trivalent inactivated influ enza vaccine (IIV3). One of the primary outcomes of the study was the efficacy of IIV3 adminis tered during pregnancy to protect infants against confirmed influenza. The vaccine efficacy was reported to be 48.8% among infants whose mothers did not have human immunodeficiency virus (HIV) infection. This means that although their mothers were immunized, 51.2% of the in fants were not protected. The question arises as to whether the infants who did not gain effective immunity were also those who were immunologically predisposed to severe disease. Hence, what was the severity of the influenza in the un protected vaccinated group as compared with the placebo group? Was there an overrepresentation of influenza infections that were severe enough to require hospitalization in the vaccinated group? If this were the case, then from a clinical per spective, the vaccine would be of limited value. Would the authors please provide data on the number o f confirmed cases of influenza that were severe enough to require hospitalization in both the vaccinated and placebo groups?
lished, acquisition of hemagglutinin antibody transplacentally or through breast-feeding1 or indirectly by preventing influenza infection in mothers and reducing transmission to their in fants may be involved. Although our study was not designed to evaluate the efficacy of the vac cine against influenza with respect to hospital ization, we observed two hospitalizations for confirmed influenza (manifested as lower respi ratory tract illness) among infants o f HlV-uninfected recipients of placebo and none among those born to IIV3 recipients. Hence, there is no evidence that infants of women who had been vaccinated with IIV3 were predisposed to more severe illness. Notably, 92% effectiveness of the vaccine against confirmed influenza leading to hospitalization2 and a 39% reduction in the risk o f clinically diagnosed influenza-like illness leading to hospitalizations3 have previously been observed in infants of women who had been vac cinated with IIV3, as compared with unexposed controls. This suggests that IIV3 vaccination of pregnant women may have greater effectiveness in protecting against severe influenza illness than against mild influenza illness in their in fants.
Ingrid Horner, M.B., B.S., M.P.H.T.M. Ralph Nanan, Dr.Med.Habil. Anthony Liu, M.B., B.S., M.P.H.
Shabir A. Madhi, M.D., Ph.D. Marta C. Nunes, Ph.D. Clare L. Cutland, M.D.
Nepean Hospital Sydney, NSW, Australia
University o f the W itwatersrand Johannesburg, South Africa [email protected]
No potential conflict of interest relevant to this letter was re ported. 1. Madhi SA, Cutland CL, Kuwanda L, et al. Influenza vaccina tion of pregnant women and protection of their infants. N Engl J Med 2014;371:918-31. DOI: 10.1056/NEJMcl412050
th e au th o r s reply: Horner et al. comment on the efficacy of IIV3 vaccination o f pregnant women in protecting infants who are younger than 24 weeks of age. Although the mechanism o f protection in infants remains to be estab
2340
N ENGLJ
M ED 3 7 i;2 4
Since publication of their article, the authors report no fur ther potential conflict of interest. 1. Schlaudecker EP, Steinhoff MC, Omer SB, et al. IgA and neu tralizing antibodies to influenza A virus in human milk: a ran domized trial of antenatal influenza immunization. PLoS One 2013;8(8):e70867. 2. Benowitz I, Esposito DB, Gracey KD, Shapiro ED, Vazquez M. Influenza vaccine given to pregnant women reduces hospital ization due to influenza in their infants. Clin Infect Dis 2010; 51:1355-61. 3. Eick AA, Uyeki TM, Klimov A, et al. Maternal influenza vac cination and effect on influenza virus infection in young in fants. Arch Pediatr Adolesc Med 2011;165:104-11. DOI: 10.1056/N EJMcl412050
N E JM .O R G
D E C E M B E R 11, 2 O I 4
Copyright © Massachusetts Medical Society 2014.
