ReviewInfluenza vaccine for pregnant women in resource-constrained countries: A review of the evidence to inform policy decisions
Introduction
Every year, seasonal influenza causes three to five million severe cases of disease and about 250,000–500,000 deaths worldwide [1]. In high-resource countries, influenza vaccine is recommended annually, and priority is given to high risk groups including pregnant women, children, the elderly, and persons with chronic medical conditions [2]. Influenza prevention in infants remains problematic. Influenza vaccines are not licensed for children younger than 6 months, and antiviral chemoprophylaxis is not licensed for children younger than 1 year [2].
While influenza burden of disease data are limited from many resource-constrained countries, the risk of severe influenza outcomes among pregnant women and young children is likely to be higher than in developed country settings. Influenza vaccines are rarely used in resource-constrained countries for several reasons; including misperceptions that influenza is not a problem in such countries, vaccine cost, program implementation challenges, and logistical issues regarding vaccine availability, expiration dates, and optimal formulation.
The observation that maternal antibodies transmitted transplacentally confer protection against influenza during a newborn's first months of life suggests a potentially cost-effective and targeted strategy against maternal and neonatal influenza in resource-constrained settings [3], [4], [5], [6]. Recently, two prospective, controlled vaccine trials conducted in resource-constrained settings demonstrated that laboratory-confirmed influenza virus infections are lower among young infants whose mothers received trivalent inactivated influenza vaccine (TIV) [7], [8]. These new data, and the implication that two high-risk groups could be protected by vaccinating pregnant women, support an evidence-based analysis of benefits and challenges of influenza vaccine programs for pregnant women in resource-constrained settings.
In this article, we review the evidence on the immunogenicity, safety and impact of maternal influenza immunization for both mother and child, and we explore issues concerning distribution, logistics, and feasibility. The objective of this review is to inform policy decisions in resource-constrained countries, which includes identifying evidence gaps to help inform needed research. A systematic review was not feasible due to the limited clinical trial data in this area and due to the broad range of topics that factor into policy decisions.
Section snippets
Burden of influenza in pregnant women
Numerous studies have documented disproportionate rates of severe influenza infection among pregnant women during 20th century pandemics. During the 1918 influenza A (H1N1) pandemic, observations of increased morbidity and mortality among pregnant women were often documented [9], [10]. During the 1957 influenza A (H2N2) pandemic, 50% of women of childbearing age who died were pregnant [11], [12], and 10% of influenza deaths were among pregnant women [13].
Large epidemiologic studies within the
Correlate of protection
While a serum hemagglutination inhibition (HAI) antibody titer ≥1:40 against the hemagglutinin protein is considered a correlate of protective immunity against influenza [49], caution should be used when interpreting HAI results from individual studies. Challenges to the use of serum HAI titer as a measure of individual protection from influenza virus infection exist. HAI is a difficult test to standardize, with non-trivial inter- and intra-laboratory variability [50], [51], [52]. The correlate
Efficacy of vaccination of pregnant women
In spite of the increased risk for severe disease in both epidemic and pandemic influenza periods, no vaccine-effectiveness studies of TIV in pregnant women have used laboratory-confirmed influenza outcomes in vaccine recipients (Table 1). However, multiple studies have shown the efficacy of TIV in young and middle-aged adults, and TIV vaccine immunogenicity in pregnant women is similar to non-pregnant women [2]. In addition, the randomized clinical trial in Bangladesh determined that TIV had a
Safety of vaccine to pregnant women and fetus
Substantial evidence from decades of evaluation demonstrates that TIV is safe for both pregnant women and their fetuses. FDA has classified FluLaval, Fluarix (GlaxoSmithKline Biologicals), and Agriflu (Novartis Vaccines and Diagnostics Limited) influenza vaccines as “Pregnancy Category B” medications, indicating that animal reproduction studies have not demonstrated a fetal risk, but there are no controlled studies in pregnant women [2]. FDA has classified all other licensed influenza vaccines
Summary
The burden of influenza among pregnant women, and the excellent safety profile and the reliable immunogenicity of TIV in this group support a recommendation that all pregnant women receive influenza vaccine to decrease complications of influenza disease during their pregnancies. Many national governments consider pregnant women to be a high-risk group for seasonal influenza complications, a designation that prioritizes them for TIV receipt. While the burden of influenza is not as well
Acknowledgements
The authors would like to thank Drs. John Boslego and Jorge Flores for their comments and guidance during the writing of this review. We also thank Kristin Bedell, Althea Burton, Jane Goett, Lauren Newhouse, and David Oxley for their valuable editorial, librarian, and support services.
Financial support: This review was supported with funding to PATH Vaccine Solutions from the Bill & Melinda Gates Foundation and Robert Wood Johnson Harold Amos Medical Faculty Development Program (Dr. Ortiz). The
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