Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine is similarly effective in preventing infant disease when given to pregnant women in high-income countries,1-7 and in middle-income countries such as Argentina, where whole-cell pertussis vaccine is used for primary immunization.8 Results supporting this finding from a study in Argentina were published in Clinical Infectious Diseases8 and showed that Tdap vaccination during pregnancy prevented pertussis in infants aged <2 months, with similar efficacy whether the vaccine is administered during the second or third trimester.

In 2012, Argentina became the first country in Latin America to implement maternal Tdap vaccination, prompted mainly by an alarming increase in pertussis-related infant mortality.9,10 As young infants are especially vulnerable to severe disease and death from pertussis, researchers evaluated the efficacy of maternal Tdap vaccination during the susceptible period before primary immunization.

They conducted a matched case-control study at 6 hospitals in 4 Argentinian provinces. The study population included infants aged <2 months. For each case, researchers attempted to enroll 5 controls matched on mother’s residential health district and attendance in a participating hospital within the same province. Pertussis cases were laboratory confirmed by conventional or real-time polymerase chain reaction.

Participants’ mothers were classified as vaccinated during current pregnancy if Tdap vaccination date was confirmed by vaccination card or immunization registry. When neither vaccination card nor immunization registry were found, the mother provided verbal confirmation of Tdap vaccination. Maternal vaccination history was verified by vaccination card or immunization registry for 94% of case patients and 93% of controls; overall, 7% of vaccination histories were confirmed verbally.

Results included 71 case patients and 300 controls. Control participants were younger than case participants (25 days vs 38 days; P <.0001) and more likely to have a history of congenital disease (12% vs 3%; P =.02). Meanwhile, case patients were more likely to be part of families with ≥3 household members <18 years of age (66% vs 51%; P =.02) or to have a household member with respiratory illness (69% vs 20%; P <.0001).

Of the 71 case patients and 300 controls, 49% and 78% had mothers who were vaccinated with Tdap during pregnancy, respectively (P <.0001). Overall, the adjusted vaccine effectiveness was 80.7% (95% CI, 52.1%-92.2%). After restricting the population to those participants whose mothers were classified as vaccinated by vaccination card or immunization registry, researchers found the adjusted vaccine effectiveness to be similar whether it was administered during the second or third trimester (77.6%; 95% CI, 39.1%-91.8% and 82.7%; 95% CI, 46.4%-94.4%, respectively).

Currently, the World Health Organization and Pan American Health Organization do not endorse routine maternal Tdap vaccination because of the lack of evidence regarding the possible interference of Tdap vaccination of pregnant women on the child’s immunologic response to whole-cell pertussis vaccine.11

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“Regardless of the vaccine type used for primary immunization, if blunting of the infant antibody response does result in reduced protection against disease, there may be a shift in pertussis disease burden from younger to older infants,” noted the study authors. They stressed that “studies evaluating the impact of maternal Tdap vaccination on older infants who have received their primary immunization, in addition to monitoring surveillance data in countries where maternal vaccination is recommended, will be critical to understanding this issue.”

References

  1. Amirthalingam G, Andrews N, Campbell H, et al. Effectiveness of maternal pertussis vaccination in England: an observational study. Lancet. 2014;384(9953):1521-1528.
  2. Baxter R, Bartlett J, Fireman B, Lewis E, Klein NP. Effectiveness of vaccination during pregnancy to prevent infant pertussis. Pediatrics. 2017;139(5).
  3. Winter K, Nickell S, Powell M, Harriman K. Effectiveness of prenatal versus postpartum tetanus, diphtheria, and acellular pertussis vaccination in preventing infant pertussis. Clin Infect Dis. 2017;64(1):3-8.
  4. Bellido-Blasco J, Guiral-Rodrigo S, Miguez-Santiyan A, Salazar-Cifre A, Gonzalez-Moran F. A case-control study to assess the effectiveness of pertussis vaccination during pregnancy on newborns, Valencian community, Spain, 1 March 2015 to 29 February 2016. Euro Surveill. 2017;22(22).
  5. Skoff TH, Blain AE, Watt J, et al. Impact of the US maternal tetanus, diphtheria, and acellular pertussis vaccination program on preventing pertussis in infants <2 months of age: a case-control evaluation. Clin Infect Dis. 2017;65(12):1977-1983.
  6. Saul N, Wang K, Bag S, et al. Effectiveness of maternal pertussis vaccination in preventing infection and disease in infants: the NSW Public Health Network case-control study. Vaccine. 2018;36(14):1887-1892.
  7. Dabrera G, Amirthalingam G, Andrews N, et al. A case-control study to estimate the effectiveness of maternal pertussis vaccination in protecting newborn infants in England and Wales, 2012-2013. Clin Infect Dis. 2015;60(3):333-337.
  8. Romanin V, Acosta AM, Juarez MDV, et al. Maternal vaccination in Argentina: Tdap vaccine effectiveness during pregnancy in preventing pertussis in infants less than 2 months of age [published online March 16, 2019]. Clin Infect Dis. doi:10.1093/cid/ciz217
  9. Romanin V, Agustinho V, Califano G, et al. Epidemiological situation of pertussis and strategies to control it: Argentina, 2002-2011 [in Spanish]. Arch Argent Pediatr. 2014;112(5):413-420.
  10. Vizzotti C, Neyro S, Katz N, et al. Maternal immunization in Argentina: a storyline from the prospective of a middle income country. Vaccine. 2015;33(47):6413-6419.
  11. Pan American Health Organization and World Health Organization. Maternal and Neonatal Immunization Field Guide for Latin America and the Caribbean. http://iris.paho.org/xmlui/bitstream/handle/123456789/34150/9789275119501-eng.pdf Published 2017. Accessed April 5, 2019.