Surveillance for adverse events after DTwP/Hib vaccination in Brazil: Sensitivity and factors associated with reporting
Introduction
In recent decades, vaccination has become an essential component of public health programs and is a decisive factor in controlling numerous infectious diseases [1]. In Japan, Sweden and England and Wales [2], a drastic reduction in the incidence of vaccine-preventable diseases has increased the perceived risk of adverse events following immunization (AEFIs), which has resulted in lower vaccination coverage [1], [2].
As early as the 1980s, concerns raised by this situation prompted countries such as United States, Canada, Cuba, India and New Zealand as well as European Union Member States to implement surveillance for adverse events following immunization (SAEFI) [3], [4], [5], [6], [7], [8]. In 1999, the World Health Organization (WHO) created the Global Advisory Committee on Vaccine Safety, which enables the WHO to respond promptly to issues of vaccine safety, as well as to assess the implications of vaccine safety for practice worldwide and for WHO policies [9], [10], [11].
In Brazil, passive surveillance for adverse events following immunization (PSAEFI) was implemented in 1984 and was initially restricted to the state of São Paulo [12]. Under the guidance of the National Immunization Program (NIP), PSAEFI coverage became nationwide in 1998 [13]. The Brazilian PSAEFI has since been the object of studies focusing on specific regions or types of events [12], [14], [15], [16]. However, to date, there have been no studies evaluating its features and performance at the national level.
Due to its simplicity, its lower cost and its capacity to reach a broad population base, passive surveillance is the strategy of choice for monitoring vaccine safety profiles [3]. However, one of its major drawbacks is its low sensitivity (i.e., the high rates of underreporting of AEFIs) [3], which has a negative impact on its power to describe AEFIs and to identify rare or unknown events [17]. Therefore the sensitivity of a passive surveillance is an important indicator to assess of its usefulness [17].
The study undertaken by Martins et al. [13] focusing the safety of the combined diphtheria-tetanus-whole-cell pertussis and Haemophilus influenzae type b (DTwP/Hib) vaccine, which was included in the routine Brazilian vaccination in 2002 [18], provided us with gold standard to estimate the sensitivity of Brazilian PSAEFI associated with DTwP/Hib. Since hypotonic-hyporesponsive episodes (HHEs) and convulsion are the most common severe AEFIs reported in Brazil, we chose those events as the main focus of our study.
The objectives of this study were to estimate the sensitivity of the Brazilian passive SAEFI, focusing on AEFIs associated with DTwP/Hib vaccination among infants less than one year of age, to investigate factors associated with reporting and to evaluate the consistency of the PSAEFI in describing the principal characteristics of AEFIs.
Section snippets
Methods
This was a descriptive study in which the population of interest was that of infants less than one year of age receiving at least one dose of the DTwP/Hib vaccine during the 2003–2004 period, at any vaccination site in Brazil.
The study area included all 26 states of Brazil and the Federal District of Brasília. Brazil is the largest country in Latin America, with a territory of approximately 8.5 million km2 and a population of approximately 190 million. The estimated mean population of infants
Results
The total number of doses administered in the 2003–2004 period was 18.7 million [22]. During that same period there were 9656 AEFIs associated with DTwP/Hib vaccine reported in infants less than one year of age. Of those, 1242 were excluded: 706 for being duplicate records (typically cases reported by primary health care unit at witch the children had been vaccinated and by hospital at witch the children had been treated), and 536 for being also associated with vaccines other than the DTwP/Hib
Discussion
The PSAEFI in Brazil has certain features that distinguish it from similar systems in developed countries such as the United States and those in the European Union [4], [26]. Their objectives are less comprehensive, and have operated exclusively under the auspices of the NIP [12], [24] and are not formally linked to a regulatory health agency. Nevertheless, a committee, created in 2008, has been charged with fostering joint activities and promoting cooperation between NIP and the regulatory
Acknowledgements
The authors are grateful to all of the staff of the NIP and to Dr. Luiza de Marilac Meirelles Barbosa in particular.
References (36)
Evaluation of safety after the events of 11 September 2001: role of cohort and case-control studies
Vaccine
(2004)- et al.
Impact of anti-vaccine movements on Pertussis control: the untold story
Lancet
(1998) Surveillance for safety after immunization: vaccine adverse event reporting system (VAERS)—United States, 1991–2001
MMWR
(2003)- et al.
Vaccinovigilance in Europe—need for timeliness, standardization and resources
Bull World Health Org
(2004) Immunization and Respiratory Infections Division—Vaccine safety. Canadian Adverse Events Following Immunization Surveillance System (CAEFISS)
(2005)- et al.
Adverse reaction surveillance system for vaccination in the republic of Cuba
Rev Cubana Med Trop
(1999) Adverse events following immunization: 1990
Indian Pediatr
(1991)- et al.
Vaccine adverse events reported in New Zealand 1900–5
N Z Med
(1997) - et al.
Immunization safety priority project at the World Health Organization
Semin Pediat Infect Dis
(2003) A global perspective on vaccine safety
Vaccine
(2004)
A global perspective on vaccine safety and public health: the global advisory committee on vaccine safety
Am J Public Health
Adverse events following diphtheria, pertussis and tetanus vaccinations and factors associated with severity
Rev Saúde Pública
Incidence of hypotonic-hyporesponsive episodes associated to the combined DTP/Hib vaccine used in Brazilian National Immunizations Program
J Pediatr (Rio J)
Surveillance system of a vaccine events and local data analysis—the experience in a middle-sized city in Brasil, 1999–2001
Vaccine
Outbreak of aseptic meningitis associated with mass vaccination with a Urabe-containing measles-mumps-rubella vaccine. Implications for immunization programs
Am J Epidemiol
Serious adverse events associated with yellow fever 17DD vaccine in Brazil: a report of two cases
Lancet
The reporting sensitivities of two passive surveillance systems for vaccine adverse events
Am J Public Health
Associated or combined vaccination of Brazilian infants with a conjugate Haemophilus influenzae type b (Hib) vaccine, a diphtheria-tetanus-whole-cell pertussis vaccine and IPV or OPV elicits protective levels of antibodies against Hib
Vaccine
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