Vaccine 33 (2015) 187–192

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Vaccine
journal homepage: www.elsevier.com/locate/vaccine

Events supposedly attributable to vaccination or immunization

during pandemic influenza A (H1N1) vaccination campaigns in Latin
America and the Caribbean
A.M. Ropero-Álvarez ∗ , A. Whittembury 1 , P. Bravo-Alcántara, H.J. Kurtis,
M.C. Danovaro-Holliday, M. Velandia-González
Comprehensive Family Immunization Unit, Pan American Health Organization, Washington, DC, USA

a r t i c l e i n f o a b s t r a c t

Article history: As part of the vaccination activities against influenza A[H1N1]pdm vaccine in 2009–2010, countries in
Received 3 June 2014 Latin American and the Caribbean (LAC) implemented surveillance of events supposedly attributable to
Received in revised form 5 September 2014 vaccines and immunization (ESAVI). We describe the serious ESAVI reported in LAC in order to further
Accepted 27 October 2014
document the safety profile of this vaccine and highlight lessons learned.
Available online 6 November 2014
We reviewed data from serious H1N1 ESAVI cases from LAC countries reported to the Pan Amer-
ican Health Organization/World Health Organization. We estimated serious ESAVI rates by age and
Keywords:
target group, as well as by clinical diagnosis, and completed descriptive analyses of final outcomes and
Events supposedly attributable to vaccines
and immunization
classifications given in country.
Vaccine safety A total of 1000 serious ESAVI were reported by 18 of the 29 LAC countries that vaccinated against
Guillain-Barré A[H1N1]pdm. The overall reporting rate in LAC was 6.91 serious ESAVI per million doses, with country
Febrile seizures reporting rates ranging from 0.77 to 64.68 per million doses. Rates were higher among pregnant women
Pandemic influenza (16.25 per million doses) when compared to health care workers (13.54 per million doses) and individuals
H1N1 with chronic disease (4.03 per million doses). The top three most frequent diagnoses were febrile seizures
(12.0%), Guillain-Barré Syndrome (10.5%) and acute pneumonia (8.0%). Almost half (49.1%) of the serious
ESAVI were reported among children aged <18 years of age; within this group, the highest proportion
of cases was reported among those aged <2 years (53.1%). Of all serious ESAVI reported, 37.8% were
classified as coincidental, 35.3% as related to vaccine components, 26.4% as non-conclusive and 0.5% as a
programmatic error.
This regional overview of A[H1N1]pdm vaccine safety data in LAC estimated the rate of serious ESAVI at
lower levels than other studies. However, the ESAVI diagnosis distribution is comparable to the published
literature. Lessons learned can be applied in the response to future pandemics.
© 2014 Published by Elsevier Ltd.

1. Introduction the elderly, children, and individuals with chronic disease [1,2].
As the use of seasonal influenza vaccine expanded, so too did the
In recent years, there has been rapid uptake in seasonal surveillance capacity to monitor Events Supposedly Attributable
influenza vaccination in the Americas; prior to the emergence of to Vaccination or Immunization (ESAVI); this terminology is com-
the influenza A (H1N1) virus, 35 out of 46 countries and territo- monly used in Latin America and the Caribbean (LAC) and is defined
ries had introduced the seasonal vaccine, compared to 13 countries as a clinical condition following vaccine administration, which may
and territories in 2004 [1]. Common target populations included or may not be related to the vaccination and which causes great
concern among the population [3]. In most countries, ESAVI surveil-
lance is passive and based on voluntary and spontaneous reports
from health providers [4].
∗ Corresponding author at: Pan American Health Organization, Comprehensive In June 2009, Dr. Margaret Chan, Director General of the World
Family Immunization Unit, Room 507, 525 Twenty Third St., NW, Washington, DC Health Organization (WHO), declared that circulation of influenza
20037-2895, USA. Tel.: +1 202 974 3706; fax: +1 202 974 3635.
A (H1N1) had reached pandemic levels [5]. From the pandemic’s
E-mail address: [email protected] (A.M. Ropero-Álvarez).
1
Current address: Department of Preventive Medicine and Public Health, Faculty onset, there were particular concerns about A[H1N1]pdm vac-
of Medicine, National University of San Marcos, Lima, Peru. cine safety, despite the proven safety of the seasonal vaccine [6].

http://dx.doi.org/10.1016/j.vaccine.2014.10.070
0264-410X/© 2014 Published by Elsevier Ltd.
188 A.M. Ropero-Álvarez et al. / Vaccine 33 (2015) 187–192

Concerns were centered around the short time frame available healthy school-aged children and adults aged 19–49 years [13]. The
for A[H1N1]pdm vaccine production, manufacturers’ use of novel final definition of target groups and goals were at the discretion of
adjuvants (AS03, MF59), and the antecedent temporal association each country.
of a previous influenza vaccine with Guillain-Barré Syndrome (GBS)
in the 1970s [7,8]. 2.5. Events under surveillance
LAC countries and territories administered approximately 144.6
million doses of A[H1N1]pdm vaccine in a series of national cam- PAHO’s A[H1N1]pdm ESAVI field guide focused on ESAVI sig-
paigns, placing LAC as one of the regions with the highest number nal detection, clusters, serious or fatal events, and rumors. Even
of doses administered [9]. Campaign timing was based on the though all ESAVI were to be reported, emphasis was given to febrile
availability of vaccine at the national level, which differed country seizures, anaphylaxis, GBS and outcomes among pregnant women.
to country; however, with the exception of Venezuela, all vacci- Countries were encouraged to use the case definitions developed
nation campaigns in LAC occurred between December 2009 and internationally under the Brighton Collaboration [14] in order to
September 2010. Venezuela vaccinated and reported after this standardize reporting and final classification [15].1
period. This paper describes serious ESAVI reported in LAC follow-
ing A[H1N1]pdm emergency vaccination to further document the
2.6. Case definition
vaccine’s safety profile and its implications for national immuniza-
tion programs (NIPs), as well as highlights lessons learned.
An ESAVI was considered serious if it resulted in death, hospi-
talization or prolongation of existing hospitalization, persistent or
2. Methods
significant disability or incapacity, or if it was considered a life-
threatening event. Only cases reported as serious ESAVI by the
2.1. Preparation for A[H1N1]pdm ESAVI surveillance in LAC
countries are included in this analysis. Serious ESAVI were fur-
ther classified at the country level following the final classifications
Since 2002, countries in LAC have had at their disposal guide-
developed by PAHO/WHO, which included whether the ESAVI was
lines for ESAVI response [10]; to support country efforts to carry out
considered related to the vaccine, related to a programmatic error,
ESAVI surveillance as part of A[H1N1]pdm vaccination campaigns,
a coincidental event or inconclusive [3,10].
efforts were made to enhance this routine surveillance across LAC.
Planning for A[H1N1]pdm vaccine safety monitoring also incorpo-
2.7. Causality assessment and final classification
rated lessons learned from the Safety of New Vaccines (SANEVA)
network, developed in 2006 to monitor adverse events related to
Causality assessment and final classification was generally
new vaccines [11].
tasked to the Ministries of Health in the region; however, depend-
The Pan American Health Organization, WHO’s Regional Office
ing on the complexity of each case, countries convened National
for the Americas (PAHO/WHO) elaborated and distributed a field
ESAVI Committees to guide the investigation and to provide final
guide specific to A[H1N1]pdm ESAVI surveillance, crisis preven-
classification. The assessment of final ESAVI outcomes, regard-
tion and management [12]. Several months before the arrival
less of final classification, was also done in country and based on
of vaccine, a workshop was held for officers in charge of ESAVI
WHO definitions, which included whether an ESAVI was recov-
surveillance from the NIP, professionals from national epidemiol-
ered/resolved, recovering/resolving, not recovered/not resolved,
ogy departments and national regulatory authorities representing
recovered/resolved with sequelae, fatal, or whether the final out-
16 LAC countries. This workshop promoted collaboration and fre-
come was unknown [16].
quent communication between all relevant actors and emphasized
PAHO established an ongoing dialogue with national author-
prompt ESAVI reporting, investigation, and final classification.
ities in charge of ESAVI surveillance to discuss and clarify any
concerns raised during case revision; particular focus was again
2.2. Surveillance period
given to febrile seizures, anaphylaxis, GBS and ESAVI during preg-
nancy. PAHO only reviewed the reported data but was not in a
PAHO asked its Member States to report A[H1N1]pdm ESAVI on
position to discard any serious A[H1N1]pdm ESAVI cases reported
a weekly basis, beginning at the start of their vaccination campaign
by countries. As mentioned before, this article includes all serious
and continuing on until 45 days following its finalization.
A[H1N1]pdm ESAVI reported by LAC countries; data was updated
for the last time in May 2012, when a final revision of country infor-
2.3. Surveillance instrument
mation was completed during a regional vaccine safety meeting.
Countries used a standardized format for A[H1N1]pdm ESAVI
reporting, which included variables of age, gender, place and date 2.8. Statistical analysis
of vaccination, date of symptom onset, timeframe between vacci-
nation and symptom onset, concomitant administration of other All data collected were consolidated into Excel and the fre-
vaccines, whether the vaccine contained adjuvant, clinical diagno- quency of serious ESAVI by age, sex and target group was calculated.
sis, clinical outcome, and ESAVI classification. Information on A[H1N1]pdm vaccine doses administered to preg-
nant women, health care workers and people with chronic health
2.4. Target populations for vaccination conditions was also obtained from countries, in order to calculate
reported rates of serious ESAVI per million doses in these groups.
Due to the initially limited quantities of available A[H1N1]pdm Given that an individual patient could present more than one ESAVI,
vaccine, in 2009, PAHO’s Technical Advisory Group (TAG) recom- the first clinical diagnosis reported by the country was selected;
mended the prioritization of target populations for vaccination, 95% confidence intervals (CI) were calculated for all rates. Descrip-
including health care workers, pregnant women and individuals tive analysis was done on final outcomes and classifications given in
with chronic illness older than 6 months of age. Depending on
a country’s epidemiological situation, resources and the capacity
of the NIP, the TAG recommended expanding vaccination to other 1
The Brighton Collaboration is an international, independent network which pro-
population risk groups, including children aged 6 months to 4 years, vides standardized methods to monitor vaccine safety.
 A.M. Ropero-Álvarez et al. / Vaccine 33 (2015) 187–192 189

country. Microsoft Excel 2010® and SPSS software package (version (8.7%), polyneuropathy (7.2%), Bell’s palsy (5.8%) and sudden death
20) were used for analysis. (4.3%) (Table 3). In this group, 58.2% (32/55) of cases were male.

3.1. Monitoring of specific A[H1N1]pdm ESAVI diagnosis

3. Results
Febrile seizures were only reported among children, with a
In LAC, 1000 serious ESAVI were reported by 18 of the 29 median age of 16 months (range from 6 months to 12 years). Time of
countries and territories that implemented vaccination campaigns onset was available for 97.5% (n = 117) of cases, with a median of 9 h
against A[H1N1]pdm. Additionally, Cuba reported 8 serious ESAVI, after vaccination (interquartile range [IQR]: 9–24 h). A total of 116
but as individual case information was not available, they were not (99.1%) cases occurred within 72 h after vaccination: 97 (80.8%) in
considered in this analysis; however, additional information has the first 24 h, 6 (5.0%) between 24 and 48 h and 3 (2.5%) between 48
been reported elsewhere [17]. The remaining 10 countries and ter- and 72 h. Febrile seizures were more frequent among males (55.7%).
ritories reported only non-serious ESAVI [18]. Country reporting The largest proportion of GBS cases was reported in adults
rates ranged from 0.77 to 64.68 serious ESAVI per million doses. (67.6%), with a median age of 29.9 years (range from 9 months–79.2
The overall reporting rate in LAC was 6.91 serious ESAVI cases per years). Date of onset was available for 92.4% (n = 97) of cases, with a
million doses (Table 1). median time of 12 days after vaccination (IQR: 5 days- 26 days). Out
By age group (n = 984), the largest percentage of serious ESAVI of the 97 cases, a total of 89 cases (91.8%) occurred within 42 days
were reported in children less than 18 years of age (49.8%); within after vaccination. No cases were reported among pregnant women.
this group, the highest number of serious ESAVI was concentrated Cases were distributed evenly between males and females.
in children less than 2 years of age (53.1%). Adults aged 18–59 years The median age of anaphylaxis cases (n = 76) was 30 years (range
represented 43.2% of serious ESAVI reported in LAC, followed by from 6 months to 70 years). Time of onset was available for 92.1%
individuals aged 60 years or older (7.0%) (Table 2). (n = 70) of cases, with a median time of 60 min after vaccination
Vaccination by sex was not available in order to calculate rates; (IQR: 60–495 min); 41 of these cases (53.9%) cases occurred in the
however, serious ESAVI were reported more frequently among first hour and 24 (31.6%) cases occurred between the first hour
males (57.8%) (n = 851). Data were only available to calculate the but within 24 h after vaccination. Anaphylaxis was more common
rate of serious ESAVI among the population target groups of preg- among women (75.4%).
nant women (16.25 cases per million doses), health care workers Among pregnant women (n = 78), the most frequent clinical
(13.54 cases per million doses) and people with chronic health diagnoses were miscarriage (57.7%), and preterm labor and deliv-
conditions (4.03 cases per million doses) (Table 2). ery (6.4%). A total of 4801,168 doses were administered to pregnant
Rates of serious ESAVI by vaccine manufacturer could not be women with an overall rate of reported events of 16.25 (95% CI:
calculated due to the absence of data on doses administered disag- 12.64–19.43) cases per million doses.
gregated by producer. Out of the total number of serious ESAVI
reported with information available on the presence of adju- 3.2. A[H1N1]pdm ESAVI final outcomes and classification
vant (n = 877), 57.8% of cases had received unadjuvanted vaccine
(Table 2). Through PAHO’s Revolving Fund for Vaccine Procurement Most reported serious ESAVI cases had a positive clinical out-
and WHO vaccine donations, approximately 20.2 million doses of come. Of the 898 serious ESAVI cases with available information on
unadjuvanted vaccine and 10.4 million doses of adjuvanted vaccine final outcome, 65.9% fully recovered, 21.0% recovered with seque-
doses were received in LAC. An additional 151 million doses were lae (miscarriages were included here), 8.0% died and 5.0% were still
procured directly from the manufacturer by Argentina, Brazil, and hospitalized at the time of the final revision of country data with
Mexico and information is not available regarding what percentage no additional information provided. Countries reported 72 deaths
of these vaccines contained adjuvant [18]. following vaccination among the approximately 144.6 million indi-
Among the serious ESAVI reported in LAC, the most frequently viduals vaccinated. The median age at death was 27.3 years (range
reported diagnoses were febrile seizures (12.0%), GBS (10.5%), acute from 6 months to 92 years). Main causes of death were reported as
pneumonia (8.0%), anaphylaxis (7.6%), seizures (6.1%) and hypo- sudden death (33.4%), acute pneumonia (18.1%), myocardial infarc-
tonic hyporesponsive episodes (HHE) (5.6%), which accounted for tion (5.6%), cerebrovascular accident (4.2%) and bronchoaspiration
almost half of all cases. All reporting rates were under 1 case per (4.2%). Most fatalities were among healthy adults >60 years (29.2%),
million doses (Table 3). followed by people with chronic illnesses (17.1%), adults (9.0%),
Among the 260 serious ESAVI reports in children less than 2 health care workers (5.6%), pregnant women (5.3%) and children
years of age, the most frequent diagnoses were febrile seizures (4.3%). Of all serious ESAVI reported in LAC, 37.8% were ultimately
(34.6%), HHE (14.2%), acute pneumonia (10.3%), non-febrile classified by countries as coincidental events (2.61 per million
seizures (8.1%) and anaphylaxis (5.4%); the same sequential order doses), 35.3% as related to vaccine components (2.44 per million
of diagnoses was observed for all children less than 18 years of age doses) and 0.5% as programmatic errors (0.03 per million doses).
(Table 3). Within this group, the majority of ESAVI cases occurred The remaining 26.4% of cases were classified as non-conclusive.
among males (52.6%). Seventy-four children less than 2 years of
age received concomitant vaccination along with A[H1N1]pdm 4. Discussion
vaccine; it was not possible to differentiate which vaccine was
responsible for the ESAVI. Information on concomitant vaccination This article represents the first overview of A[H1N1]pdm vac-
for the most frequently reported ESAVI is shown in Table 4. cine safety data in LAC following widespread vaccination in 2010
Among the 425 serious ESAVI reports in adults aged 18–59 years, and replaces preliminary information reported previously [18].
GBS (12.5%), anaphylaxis (10.6%), miscarriage (9.4%) acute pneu- Across the region, ESAVI surveillance systems were able to detect
monia (6.1%), Bell’s palsy (5.9%) and seizures (4.0%) were the most safety signals following A[H1N1]pdm vaccination. While reported
common diagnoses, both for healthy individuals and those with rates of serious ESAVI varied greatly by country, they were consis-
chronic conditions (Table 3). The majority of cases (72.2%) were tent with the literature and contributed to a better understanding
female. the vaccine’s safety profile [19–24].
Among older adults (n = 69), the most common clinical diag- Countries’ ability to conduct causality assessments varied sub-
noses were GBS (26.1%), acute pneumonia (14.5%), anaphylaxis stantially and data limitations at the regional level restricted
190 A.M. Ropero-Álvarez et al. / Vaccine 33 (2015) 187–192

Table 1
Serious ESAVI reported by LAC countries and territories.

Countrya Number of doses Reported number of Rate per million doses 95% C.I.
administered serious ESAVI

Brazil 92,000,000 612 6.65 6.12–7.18

Mexico 26,903,232 154 5.72 4.82–6.63
Argentina 8,258,009 109 13.20 10.72–15.68
Chile 3,084,124 28 9.08 5.72–12.44
Ecuador 973,480 20 20.54 11.54–29.55
Colombia 2,037,301 16 7.85 4.01–11.70
Honduras 1,810,783 12 6.63 2.88–10.38
Paraguay 1,087,661 12 11.03 4.79–17.28
Peru 2,237,053 10 4.47 1.70–7.24
Bolivia 1,249,049 5 4.00 0.49–7.51
Uruguay 538,057 5 9.29 1.15–17.44
Venezuela 500,000 4 8.00 0.16–15.84
Costa Rica 180,000 3 16.67 0.00–35.53
Nicaragua 251,759 3 11.92 0.00–25.40
Suriname 24,674 3 64.68 0.00–137.86
Panama 254,286 2 7.87 0.00–18.77
Cayman Islandsb 2,318 1 – –
Guatemala 1,295,742 1 0.77 0.00–2.28
Other countriesc 1,934,065 0 – –
Total 144,621,593 1000 6.91 6.49–7.34
a
Cuba did not report individual case information for reported serious ESAVI, and therefore, it was not included in the analysis. In the country, a total of 1123,526 doses
were administered and 3401 ESAVI cases were reported, 8 of which were classified as serious.
b
Rate not calculated due to small population size.
c
Includes doses administered in Bahamas, Barbados, Belize, Bermuda, El Salvador, Grenada, Guyana, Montserrat, Trinidad and Tobago, and Turks and Caicos Islands,
countries and territories that did not report serious ESAVI cases.

calculating rates among certain target groups and other in-depth reporting (in relation to severity, and timing of adverse events) and
analyses. Despite such limitations, lessons learned have helped inconsistency in the quality and completeness of reports.
to strengthen current ESAVI surveillance systems in LAC, bet- The reported rate of serious ESAVI varied greatly between coun-
ter preparing them to respond to future pandemics and other tries but is consistent with the A[H1N1]pdm literature and with
immunization-related emergencies. what has been observed in seasonal influenza campaigns [19–24].
The rate of serious ESAVI reported in LAC (6.91 per million doses) Data variability by country is also likely due to the heterogeneous
was significantly lower than the rate reported in Europe (38.2 per capacity of the national surveillance systems to detect ESAVI and
million doses) and slightly lower than in the United States (8.8 per fully investigate them [25].
million doses) and China (7.9 per million doses), where ESAVI noti- Across LAC, the rate of GBS (0.73 cases per million doses across
fication was also through passive surveillance systems [19–21]. all ages, 95%CI: 0.59–0.86) fell within what has been published in
Nevertheless, the doses administered in LAC were almost three similar studies worldwide (0.8 to 1.9 cases per million vaccinations)
times higher than in Europe, the United States and China. The lower [19,20,23], while the rate of anaphylaxis (0.53 cases per million
regional rate may be explained by either the lower occurrence of doses across all ages) was lower than that reported from Europe and
cases or, more likely, by the nature of the reporting systems in the United States, [19,20,23] and similar to that reported from China
LAC, which may have allowed for more under-reporting, biased [21]. Misdiagnosis may have occurred, for example onset of GBS

Table 2
Reported serious ESAVI following A[H1N1]pdm vaccination by demographic characteristics and vaccine type, LAC.

Characteristic Reported number of serious ESAVI % Number of doses Reported rate per million doses 95%CI

Age (years) n = 984

≤2 260 26.4 – –
2–4 110 11.1 – –
5–17 120 12.2 – –
18–59 425 43.2 – –
≥60 69 7.0
Sex n = 851
Female 359 42.2 – –
Male 492 57.8 – –
Vaccination group n = 997
Children < 18 yearsa 434 43.4 – –
Adultsb 243 24.3 – –
Chronic health conditionsc 138 13.8 33,492,168 4.03 3.35–4.65
Health care workers 78 7.9 5,833,641 13.54 10.56–16.18
Pregnant womend 78 7.8 4,801,168 16.25 12.64–19.43
Adults ≥60 y 26 2.6 – –
Type of vaccine n = 877
Adjuvanted 370 42.2 – –
Non adjuvanted 507 57.8 – –
a
Does not include children with chronic health conditions or pregnant women.
b
Healthy adults (18–59 years old); does not include chronic health conditions, health care workers, pregnant women or adults 60 years old or over.
c
Includes people of all ages.
d
May include pregnant women <18 years of age.
 A.M. Ropero-Álvarez et al. / Vaccine 33 (2015) 187–192 191

Table 3
Clinical diagnosis of serious ESAVI following A[H1N1]pdm vaccination by age groupa , LAC.

Clinical Diagnosis Reported number % Rate per 95% CI ≤2 years 2–4 years 5–17 years 18–59 years ≥60 years
of serious ESAVI million doses

Febrile seizures 120 12.0 0.83b 0.68–0.98 90 25 5 – –

Guillain-Barré syndrome 105 10.5 0.73 0.59–0.86 4 11 16 53 18
Acute Pneumonia 80 8.0 0.55 0.43–0.67 27 8 9 26 10
Anaphylaxis 76 7.6 0.53 0.41–0.64 14 1 6 45 6
Seizures 61 6.1 0.42 0.32–0.53 21 9 13 17 1
Hypotonic–hyporesponsive episode 56 5.6 0.39b 0.29–0.49 37 10 9 – –
Miscarriage 45 4.5 0.31 0.22–0.40 – – 5 40 –
Encephalitis, myelitis, 35 3.5 0.24 0.16–0.32 7 1 7 14 3
encephalomyelitis and
encephalopathy
Bell’s palsy 31 3.1 0.21 0.14–0.29 1 – 1 25 4
Sudden deathc 26 2.6 0.18 0.11–0.25 4 3 3 13 3
Syncope 22 2.2 0.15 0.09–0.22 1 3 3 14 1
Polyneuropathy 22 2.2 0.15 0.09–0.22 5 1 5 6 5
Paralytic syndromed 19 1.9 0.13 0.07–0.19 3 2 2 11 1
Ataxia 13 1.3 0.09 0.04–0.14 3 6 4 – –
Thrombocytopenic purpura 13 1.3 0.09 0.04–0.14 3 5 3 2 –
Other 276 27.6 1.91 1.68–2.13 40 25 29 159 17
Total 1000 100.0 6.91 6.49–7.34 260 110 120 425 69
a
Data on age group was not available for 16 cases of serious ESAVI.
b
Rates per million doses were calculated using the total number of doses applied across all age groups, as the total number of doses applied in certain age and risk groups
was not available.
c
Includes two infant deaths.
d
Includes the diagnosis of Paralytic Syndrome, paresis, monoplegia and hemiplegia.

Table 4
Serious ESAVI following A[H1N1]pdm in children less than 2 years of age and number and percentage of children who received concomitant vaccination.

Clinical diagnosis Reported number Number of children who received Other vaccines administered
of serious ESAVI concomitant vaccination (%)

Febrile seizures 90 27 (30.0) 4 DPT-Penta; 17 PCV; 4 OPV; 2 HepB; 1 MMR

Hypotonic–hyporesponsive episode 37 10 (27.0) 7 DPT-Penta; 6 OPV; 3 PCV; 1 rotavirus
Acute pneumonia 27 4 (14.8) 2 Seasonal influenzal; 2 PCV; 1 meningococcal C
Non febrile seizures 21 6 (28.6) 3 OPV; 3 Penta; 3 PCV
Anaphylaxis 14 5 (35.7) 3 PCV-10; 2 DPT-Penta

may have been to soon to be plausible and some cases diagnosed regulatory bodies. Adequate staff training must take place before a
as anaphylaxis occurred more than 24 h following vaccination. vaccine is used, with emphasis on data collection and analysis. Sec-
Among serious ESAVI reported in pregnant women, more than ond, countries should prioritize collecting baseline data regarding
half involved miscarriage (57.5%). Our data did not suggest any specific health outcomes, to be able to better document a vac-
safety signals in this group. These findings were similar to those cine’s safety profile. Third, core reporting ESAVI variables should
in other countries including the United States [26]. Internationally, be disseminated to countries, including the periodicity of report-
data from A[H1N1]pdm vaccine surveillance did not identify safety ing to the regional level, to ensure collecting harmonized safety
concerns among either pregnant women or their infants [26–30]. data, and thus, enabling a better comparison and pooled analysis
Given the nature of passive reporting systems, national at the regional and global level. Additionally, there is still a need to
A[H1N1]pdm ESAVI surveillance systems generally could not pro- continue strengthening and standardizing the process of causality
vide evidence of a causal association between vaccination and assessment by national safety committees.
reported serious ESAVI. Despite regional efforts to standardize this Finally, countries should work to address specific limitations of
process, including fostering active participation and technical guid- their ESAVI surveillance systems, as identified during the A[H1N1]
ance on the part of National ESAVI Committees, countries’ ability pandemic, in order to improve future pandemic response, as well
to assess causality varied substantially. Data reported in this article as ESAVI surveillance in general.
is based on countries’ classifications of their own cases; additional Given their important limitations (underreporting, biased
information, such as medical files and death certificates, to con- reporting, differential reporting, etc), passive surveillance systems
firm classifications, was not available to PAHO. It is also likely are not designed to confirm associations between vaccines and
that the Brighton Collaboration case definitions were used incon- ESAVI, their main role is to generate safety signals deserving further
sistently country to country. While countries were requested to investigation in analytical studies. To properly investigate safety
report data on a weekly basis, information was often reported less signals, well designed active surveillance systems and observa-
frequently. Additional data limitations include the lack of reliable tional studies are needed. For this reason, PAHO is working toward
denominators for all targeted age/risk groups, or by type of vac- the development of a hospital-based active ESAVI surveillance
cine (adjuvanted or not), which limited the calculation of ESAVI system, to allow epidemiologically valid verification of suspected
incidence rates. associations, even when events are rare [31].
The experience of LAC during the response to the A[H1N1] pan-
demic provide valuable lessons learned in strengthening current Acknowledgements
ESAVI surveillance systems. First, the cornerstone of effective mon-
itoring of vaccine safety is the development of close collaboration The authors would like to acknowledge the commitment
within a country between NIPs, epidemiology departments and of national immunization programs throughout LAC to ESAVI
192 A.M. Ropero-Álvarez et al. / Vaccine 33 (2015) 187–192

surveillance and reporting as part of the A[H1N1]pdm vaccination [13] Pan American Health Organization. Technical Advisory Group on Vaccine-
campaigns. We would also like to thank the national immuniza- Preventable Diseases. Final Recommendations on Pandemic Influenza;
26 August 2009. Available at: http://www.paho.org/english/ad/fch/im/
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