Pertussis vaccination during pregnancy in Vietnam: Results of a randomized controlled trial Pertussis vaccination during pregnancy

Abstract

A pertussis vaccination during pregnancy has recently been adopted in several countries to indirectly protect young infants. This study assessed the effect of adding a pertussis component to the tetanus vaccination, in the pregnancy immunization program in Vietnam.

A randomized controlled trial was performed. Pregnant women received either a Tdap (tetanus, diphtheria acellular pertussis) vaccine or a tetanus only vaccine between 19 and 35 weeks’ gestational age. Immunoglobulin G (IgG) against tetanus (TT), diphtheria (DT), pertussis toxin (PT), filamentous hemaglutinin (FHA) and pertactin (Prn) were measured using commercial ELISA tests, at baseline, 1 month after maternal vaccination, at delivery, and in infants from cord blood and before and after the primary series (EPI: month 2-3-4) of a pertussis containing vaccine.

Significantly higher geometric mean concentrations (GMC) were observed for all 3 measured pertussis antigens in the offspring of the Tdap group, up to 2 months of age. One month after completion of the primary infant vaccination schedule, anti-Prn GMC, but not anti-PT and anti-FHA GMCs, was significantly (p = 0.006) higher in the control group.

Maternal antibodies induced by vaccination during pregnancy close the susceptibility gap for pertussis in young infants. Limited interference with the infant vaccine responses was observed. Whether this interference effect disappears with the administration of a fourth vaccine dose is further studied.

Introduction

In 2008, the World Health Organization (WHO) estimated that there were 16 million pertussis cases worldwide [1]. Most cases occur in low- and middle-income countries (LMICs) [2], and case-fatality rates (CFR) for infants in developing countries are as high as 4%. Global coverage of the 3 vaccine doses for DTP (Diphtheria, Tetanus, Pertussis) for infants is as high as 84% [3]. Despite universal infant vaccination, the disease has re-emerged in some industrialized countries, resulting in morbidity and mortality in young infants who are not fully vaccinated [4]. Adolescents and young adults are susceptible to pertussis due to waning antibodies after vaccination (for both aP (acellular pertussis) and wP (whole cell pertussis) vaccines) and declining naturally acquired immunity [5], [6]. They represent a source of infection for newborns. It is likely that the shift in ages of those diagnosed with pertussis that has been observed in industrialized countries will eventually be observed in developing countries [7], depending on the vaccine that is used in infancy. The WHO recommends the use of wP vaccines in the Expanded Programme on Immunisation (EPI) [8] whenever a 3 + 1 infant-only schedule is used, but aP vaccines can be chosen when coverage decreases due to wP side effects [1].

Protection against infectious diseases at birth is provided in part by maternal antibodies transferred through the placenta and lactation [9], [10]. IgG pertussis antibodies have a half-life of 6 weeks [11]. The amount of antibodies transmitted depends on the placental function and on the maternal antibody concentration [12]. After pertussis vaccination/infection during childhood, antibody levels decline by childbearing age [13]. Therefore, the amount of anti-pertussis maternal antibodies transmitted is often low. Thus, increasing the load of maternal antibodies by maternal vaccination is, with the currently available vaccines, the best way to offer protection to newborns [14], [15], [16], [17]. Some countries recommend pertussis vaccination during pregnancy (including the USA, UK, Belgium, and others). However, no studies were performed in LMICs, where the background epidemiology and vaccination statuses are different.

In Vietnam, pertussis vaccination began in 1985. Prior to that, the incidence of pertussis was up to 84.4/100,000 (1984) [18]. Overall, the reported incidence is now low (2012–2013: 0.1/100,000 to 0.06/100,000 [18]). Nevertheless, between 95 and 108 pertussis cases were recorded in 2011–2013, and over 50% of those cases occurred in infants under one year of age. In 2014, 92 out of 102 pertussis cases were reported in infants aged less than 6 months [19]. Cases are identified and confirmed based on a clinical diagnosis; laboratory confirmation is not obtained because standard laboratory diagnostic equipment is not available at the community level, and hospital diagnoses are not routinely reported. Therefore, underreporting and underdiagnosis is highly probable.

The aim of the present study was to assess the effect of vaccinating pregnant women in Vietnam with an aP vaccine, on the amount of transferred maternal antibodies and the possible interference of the vaccine with humoral immune responses in the infants.