Higher Tetanus Toxoid Immunity 2 Years After PsA-TT Introduction in Mali

In recent years, conjugate vaccines that link the polysaccharides on the outer surface of bacterial pathogens to protein carriers such as tetanus toxoid (TT) have been developed to protect against Neisseria meningitidis, Haemophilus influenzae type b (Hib), Streptococcus pneumoniae, and other pathogens [1]. Conjugate bacterial vaccines have markedly improved prevention and control efforts beyond results obtained with polysaccharide vaccines alone [2]. Conjugate vaccines have had significantly greater impact than polysaccharide vaccines because the presence of a carrier protein transforms the T-cell–independent immune response into a T-cell–dependent response, inducing immunologic memory and a strong immune response even among infants [3]. In addition, meningococcal, pneumococcal, and Hib conjugate vaccines have been shown to effectively prevent the acquisition of nasopharyngeal carriage of vaccine strains [2]. The 2010 introduction of an affordable group A meningococcal polysaccharide–TT protein conjugate vaccine, PsA-TT, or MenAfriVac, through mass vaccination campaigns targeting individuals aged 1–29 years in the African meningitis belt, has led to a dramatic decrease in group A meningococcal disease [4]. In addition to 10 µg of group A polysaccharide, PsA-TT contains 10–33 µg of TT [5], a level similar to other TT-containing vaccines. As a result, PsA-TT may boost immunity to tetanus in populations, adding benefit beyond prevention of meningococcal disease. Boosting tetanus immunity would be especially beneficial in resource-limited settings where tetanus incidence is highest and in areas where not all individuals have had prior exposure to sufficient doses of TT-containing vaccines to maintain immunity. Currently, the World Health Organization (WHO) recommends that 3 doses of a TT-containing vaccine be administered in the first year of life as part of routine immunization programs with 2 booster doses of TT-containing vaccines given during childhood followed by vaccination of pregnant women to prevent neonatal tetanus [6]. Meeting the Global Vaccine Action Plan's (GVAP) target of 90% coverage nationally and >80% coverage with at least 3 doses of diphtheria-tetanus-pertussis vaccine in every district by 2015 remains a challenge for many low- and middle-income countries. By 2013, an estimated 66% of countries achieved the former target [7], and by 2012, 30% achieved the latter target worldwide [8]. Evidence suggests that 3 doses of TT-containing vaccine in the first year of life provides 3–5 years of protection, a booster dose between 4 and 7 years of age protects through adolescence, and another booster in adolescence protects through adulthood for 20–30 years [9]. However, vaccination schedules and vaccination coverage vary by country. In Mali, national immunization includes administration of pentavalent diphtheria, TT, pertussis, H. influenzae, and hepatitis B vaccine at 6, 10, and 14 weeks, with additional TT vaccination during pregnancy [10]. Mali does not administer adolescent TT boosters as part of its routine immunization program [10]. WHO-UNICEF estimates that in 2010, 82% of 12- to 23-month-olds in Mali received at least 1 dose of TT-containing vaccine, and 76% received all 3 recommended Expanded Programme on Immunization (EPI) doses [11]. Tetanus remains an ongoing challenge in some low- and middle-income countries [12], and an estimated 58 000 neonatal deaths due to tetanus occurred worldwide in 2010 [13]. Several countries located in the African meningitis belt, including Mali, Niger, Nigeria, and Chad had not eliminated maternal and neonatal tetanus as of mid-2014 [14]; only 11% of countries in the African region achieved both of the GVAP coverage goals by 2012 [15]. Enhanced protection against tetanus might be achieved as a result of vaccination with PsA-TT. To determine whether PsA-TT boosts tetanus immunity, we assessed the impact of the PsA-TT in Mali on population-level TT immunity by quantifying TT-specific IgG levels before and 2 years after the December 2010 PsA-TT mass vaccination campaign.