In October 2014, the Brazilian Ministry of Health’s Epidemiological Surveillance Center “Prof. Alexandre Vranjac” (CVE) in São Paulo, Brazil published a “technical report” on the diphtheria, tetanus and pertussis vaccine (Tdap).1 In that report, the CVE stated that the Tdap vaccine would be included in Brazil’s National Vaccination Schedule for pregnant women.
Considering the epidemiological situation of the [pertussis] disease and the need to protect the mother-child pair, the Tdap vaccine will be incorporated into the National Vaccination Schedule for pregnant women and health professionals (anesthesiologist, gynecologist, obstetrician, neonatologist, pediatrician, nurse, and nursing technician) who care for newborns in maternity wards and nurseries/neonatal ICUs.1
A retrospective study published in the journal BMC Infectious Diseases in 2015 highlights the growing incidence of pertussis (whooping cough) in Brazil from 2007 to 2014. Using data obtained from case notification forms, the study identified a total of 80,068 “suspected cases” of pertussis in Brazil during that seven-year period.2 Another study published in Autopsy Case Reports last year cited the increasing number of deaths from pertussis in Brazil in recent years, particularly in 2013.3
In 2013, 109 pertussis-related deaths were reported—a number 7-fold higher than the average number of deaths reported annually in the period from 2001 to 2010. More than 80% of the deaths occurred in infants younger than 3 months of age.3
It is understandable that the Brazilian government was concerned about the upward trend in pertussis infections. By the end of 2014, following the October report from the CVE, the Brazilian Ministry of Health announced the introduction of the Tdap vaccine for all pregnant women in the country,3 and the Brazilian National Immunization Program (NIP) had begun the vaccinations.2 The policy change had been expected for many months. Earlier in 2014, at a meeting of the World Health Organization’s (WHO) Strategic Advisory Group of Experts (SAGE), the group had written in a background paper…
[Brazil] will recommend Tdap in the routine immunization programme for pregnant women from 2014 onward.4 .
The CVE report recommended the Tdap vaccine be given to women between the 27th week and 36th week of their pregnancy, and that it could also be administered up to 20 days prior to the expected date of birth.1 The report specified the Tdap produced by GlaxoSmithKline (GSK) of the United Kingdom as the one to be used. GSK has a technology transfer agreement with Brazil’s Butantan Institute for the production of the Tdap vaccine5 in Brazil.
The CVE report listed the following ingredients in the GSK/Butantan Institute Tdap vaccine:
- Diphtheria toxoid—not less than 2 International Units (IU)
- Tetanus toxoid—not less than 20 International Units (IU)
- Bordetella pertussis antigen
- Pertussis toxoid—8 mcg
- Filamentous haemagglutinin—8 mcg
- Pertactin—2.5 mcg
- Adsorbed hydrated aluminum hydroxide (Al (OH ) 3) and aluminum phosphate (AlPO4)
- Excipients: aluminum hydroxide , aluminum phosphate , sodium chloride and water for injection. Contains formaldehyde residues, polysorbate 80 and glycine1
GSK’s Tdap product is internationally known under the brand name Refortrix® or, more commonly, Boostrix®), and it has been licensed in Brazil for more than a decade.6 In addition to the ingredients listed above for Boostrix, the following growth medium and process ingredients are used in manufacturing the vaccine:
- modified Latham medium derived from bovine casein
- Fenton medium containing bovine extract
- Stainer-Scholte liquid medium
- aluminum hydroxide7
According to GSK, neither the safety nor effectiveness of Boostrix have been established in pregnant women.8 The package insert for Boostrix reads:
A developmental toxicity study has been performed in female rats at a dose approximately 40 times the human dose (on a mL/kg basis) and revealed no evidence of harm to the fetus due to BOOSTRIX. Animal fertility studies have not been conducted with BOOSTRIX. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, BOOSTRIX should be given to a pregnant woman only if clearly needed.8
Despite this cautionary information, the Brazilian government has been vaccinating tens of thousands, if not hundreds of thousands, of pregnant women in its country during the past year. A large portion of these pregnancies are occurring in Brazil’s northeastern region, notably in the state of Pernambuco—the country’s fastest growing population center.9 10
1 Centro de Vigilância Epidemiológica “Prof. Alexandre Vranjac” (CVE). INFORME TÉCNICO–VACINA DIFTERIA, TÉTANO E COQUELUCHE (dTpa). cve.saude.sp.gov.br October 2014.
2 Guimarães LM, Neves da Costa Carneiro EL, Carvalho-Costa FA. Increasing incidence of pertussis in Brazil: a retrospective study using surveillance data. BMC Infect Dis2015; 15: 442.
3 Palazzi Sáfadi MA. Pertussis in young infants: a severe vaccine-preventable disease. Autops Case Rep April-June 2015; 5(2): 1-4.
4 World Health Organization (WHO). WHO SAGE pertussis working group: Background paper, SAGE April 2014. WHO.int April 2014.
5 Instituto Butantan. vaccines. Butantan.gov.br.
6 de Carvalho AP, Pereira EMC. Acellular pertussis vaccines for adolescents. J PediatrJuly 2000; 82(3).
7 Vaccine Ingredients and Manufacturer Information. CarProCon.org
8 GlaxoSmithKline (GSK). Package Insert for Boosterix. us.GSK.com
9 Bevins V. Brazil’s historically poor northeast finally gets its boom. Los Angeles Times May 24, 2012.
10 Sells H. Brazil’s Northeast Emerging as Economic Powerhouse. CBN News July 23, 2012.