Dengue seropositivity in a randomly selected sample from Yucatan analyzed in the context of dengue cases reported between 1996 and 2006

Abstract

Introduction: Dengue virus (Denv) was first reported in Yucatan in 1979. Since then, Denv has been associated with multiplecases of Dengue Fever (DF) and Dengue Hemorrhagic Fever (DHF), becoming an endemic disease in Yucatan, Mexico.

Objectives: To determine the seropositivity to dengue infections in random sample of the Yucatan general population in 1996and 2006 and analyze it along with the reported dengue cases in the state during that ten-year-period.

Methods: Samples from the randomly selected participants were tested for IgG dengue antibodies in both serosurveys, whilelaboratory confirmed DF and DHF were obtained from the epidemiologic surveillance system from 1996 to 2006.

Results: The overall seropositivity to Denv infection was 59.9% in 1996 and 81.5% in 2006, according to the serosurveys. Theincrease in seropositivity can be at least partially explained by the peak in DF and DHF cases that took place in 1997, as reportedin the surveillance system.

Conclussion: Data drawn from the 1996 and 2006 serosurveys showed an increase of seropositivity to Denv infections, which canpartially be explained by the 1997 outbreak in the Yucatan. While seroprevalence studies were useful to identify the proportion ofseropositive population, the case reports from the epidemiologic surveillance system were useful to identify the epidemic year,meaning that both sources of information are complementary to better understand the Denv dynamics during the ten-year-periodelapsed between 1996 and 2006.

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http://jer.sciedupress.com Journal of Epidemiological Research 2017, Vol. 3, No. 1
ORIGINAL ARTICLES
Dengue seropositivity in a randomly selected sample
from Yucatan analyzed in the context of dengue cases
reported between 1996 and 2006
S. Gómez-Carro1, N. Méndez-Domínguez∗2, J. F. Mendez-Galván3
1Hospital General “Dr. Agustín O’Horán”, Mérida, México
2Centro de Investigación y de Estudios Avanzados del IPN, Departamento de Ecología Humana, Mérida, México
3Hospital Infantil de México Federico Gómez, México City, México
Received: August 10, 2016 Accepted: September 18, 2016 Online Published: September 19, 2016
DOI: 10.5430/jer.v3n1p23 URL: http://dx.doi.org/10.5430/jer.v3n1p23
ABS TR ACT
Introduction:
Dengue virus (Denv) was first reported in Yucatan in 1979. Since then, Denv has been associated with multiple
cases of Dengue Fever (DF) and Dengue Hemorrhagic Fever (DHF), becoming an endemic disease in Yucatan, Mexico.
Objectives:
To determine the seropositivity to dengue infections in random sample of the Yucatan general population in 1996
and 2006 and analyze it along with the reported dengue cases in the state during that ten-year-period.
Methods:
Samples from the randomly selected participants were tested for IgG dengue antibodies in both serosurveys, while
laboratory confirmed DF and DHF were obtained from the epidemiologic surveillance system from 1996 to 2006.
Results: The overall seropositivity to Denv infection was 59.9% in 1996 and 81.5% in 2006, according to the serosurveys. The
increase in seropositivity can be at least partially explained by the peak in DF and DHF cases that took place in 1997, as reported
in the surveillance system.
Conclussion:
Data drawn from the 1996 and 2006 serosurveys showed an increase of seropositivity to Denv infections, which can
partially be explained by the 1997 outbreak in the Yucatan. While seroprevalence studies were useful to identify the proportion of
seropositive population, the case reports from the epidemiologic surveillance system were useful to identify the epidemic year,
meaning that both sources of information are complementary to better understand the Denv dynamics during the ten-year-period
elapsed between 1996 and 2006.
Key Words: Dengue, Seroprevalence, Yucatán, Elisa, Immunoglobulin G
1. INTRODUCTION
Dengue virus (Denv) preventive strategies for eradicating
Aedes aegipty were adopted by Mexican government in the
1960’s decade, and as a result, Aedes borne diseases were
not reported for over a decade. By the end of the 1970’s,
in Mexico, the first confirmed dengue cases were reported
in Chiapas. Dengue Fever (DF) cases were confirmed in
Yucatan in 1979, rapidly followed by major epidemics in
the State for the next five years, and with the appearance of
dengue serotype 4 in Yucatan during 1984, Dengue Hemor-
rhagic Fever (DHF) incidence increased dramatically. The
serosurveys conducted during the 1980’s decade showed a
∗Correspondence:
N. Méndez-Domínguez; Email: ninuxka@hotmail.com; Address: Centro de Investigación y de Estudios Avanzados el IPN
Unidad Mérida, Departamento de Ecología Humana, Unidad Mérida Km, 6 Antigua carretera a Progreso Apdo, Cordemex 97310, Mérida, Yucatán,
México.
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http://jer.sciedupress.com Journal of Epidemiological Research 2017, Vol. 3, No. 1
positivity close to 70% of the urban population, suggested
a possible underreport of dengue cases at that time in Yu-
catan.[1–3]
Since then, Denv has been associated in Yucatan with mul-
tiple fatal cases, Dengue Fever DF and DHF, becoming an
endemic disease which had been favored by the abundance
of Aedes aegypti, the main dengue vector in the region.[4,5]
In Mexico, and particularly in Yucatan, experts have consid-
ered that the number of unreported DF cases were ten times
more than reported by the epidemiological surveillance sys-
tem. The prevalence of antibodies due to historic dengue
infections could help to understand the Denv transmission if
we consider the possibility that cases diagnosed and reported
are not reflecting accurately the number of people that have
been infected with at least one serotype of Denv.[6]
The recent Denv epidemic outbreak experienced during 2015
in Yucatan (with 17,016/1,502 Suspected/Confirmed Dengue
Reported Cases) motivated us to look back and analyze the
Denv dynamics over a ten-year period, including data drawn
from both, passive surveillance and two seroprevalence stud-
ies.[5]
Our aim in this study is to determine the seropositivity to
dengue infections in a random sample of the Yucatan general
population in 1996 and 2006 and to analyze that information
considering the number of dengue confirmed cases reported
by the epidemiologic surveillance system during that ten-
year-period.
2. METHODS
2.1 Seroprevalence surveys
We chose the ten-year-period elapsed between 1996 and
2006 because the main author supervised and conducted
serosurveys in those years, but also considering the access
and availability of Denv reported cases in Yucatan during
that period. The studies were undertaken in Yucatan, Mexico.
First, in 1996 the participating communities were randomly
chosen from a list of the 106 municipalities, including all
communities with
≥
15,000 inhabitants, according to the
official demographic records from the National Council of
Population (CONAPO in Spanish) for 1996. The six selected
municipalities were: Progreso, Uman, Chemax, Hunucma,
Tizimin and Merida. As municipalities include smaller pop-
ulation units called communities, for the 2006 serosurvey,
the list of communities from the municipalities selected for
the 1996 serosurvey was randomized, that means that the
participating individuals in 1996 and 2006 belonged to the
same municipalities that were selected for the 1996 sero-
survey, but were not necessarily from the same community.
The population from the randomized municipalities together
account for 75.3% of the total state population (1,830,893
inhabitants, according to CONAPO estimates for 2006).
Participants were randomly selected without replacement
based on the geographic location of their homes through a
geographical mapping system, by listing, numbering and
then randomizing the row number of the districts and/or
quadrants of the selected communities in an excel dataset.
Only one participant was selected per household, and that
participant was also selected randomly from among the in-
habitants of the household, as every member of the family
was coded with a number and chosen randomly in situ. Par-
ticipants were visited at their homes simultaneously during
the low dengue transmission season (dry season from January
to April).
These district, quadrant, house and family member selection
procedures were followed in both, the 1996 and the 2006
serosurveys, as both surveys were conducted and supervised
mainly by the same research group and principal investigator.
All participants signed an informed consent form voluntarily
(in the case of minors, legal tutors signed consent forms). An
inclusion criterion was that participants were only eligible if
they had no signs or symptoms of any acute febrile disease
in the previous eight weeks. We estimated a sample size for
1996 based on the population size at the time, and then in
2006, we repeated the sample size calculation with the up-
dated population size; the samples for both studies was based
on a prevalence of 0.5 with a maximum error of 5% and 95%
bilateral confidence intervals [n = NZ
α2
/(N-1)+Z
α2
e
2
)], ob-
taining as a result a minimum sample of 352 for 1996 and
368 for 2006. The sample was distributed to proportionally
represent each age group.
For both serosurveys, blood samples consisted of 5 ml of
venous blood, drawn by conventional techniques from the
forearm of the participants and transferred into Vacuteiner
R

glass vials with serum separator; blood was preserved be-
tween 4 to 8 degrees Celsius to be subsequently centrifuged
at 5,000 rpm for 10 minutes and finally transferred to the
Institute of Epidemiological Reference (INDRE in Spanish).
At the INDRE the serum was separated and tested for dengue
IgG antibodies with Panbio
R

dengue IgG Indirect ELISA
kits. Panbio
R

standardized unit cutoff points were used for
negative (< 9 UPB), indeterminate (9-11 UPB) and positive
(
≥
11 UPB) results, with specificity of 100 and sensitivity of
97.9.
2.2 Confirmed Denv cases between 1996 and 2006
For the confirmed Denv cases reported between 1996 and
2006, we downloaded the morbidity annual records from the
Board of Health, Department of Epidemiology web page,
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where DF and DHF cases are reported separately. Confirmed
Denv cases between 1996 and 2006 were those with acute
dengue clinical manifestations that were sampled and tested
positive for IgM antibodies using Panbio
R

Elisa that were
finally registered in the Epidemiologic Surveillance System.
Table 1. Seropositivity to IgG indirect dengue Elisa in a random sample of Yucatan, Mexico
Age
group
Samples Positive Proportion CI 95% Samples Positive Proportion CI 95%
1996 2006
0-4 18 4 0.22 0.03 0.41 15 3 0.20 0.00 0.40
5-14 105 32 0.30 0.22 0.39 59 30 0.51 0.38 0.64
15-24 77 55 0.71 0.61 0.82 66 52 0.79 0.69 0.89
25-44 89 67 0.75 0.66 0.84 126 116 0.92 0.87 0.97
45-64 47 39 0.83 0.72 0.94 64 61 0.95 0.90 1.00
≥ 65 16 14 0.88 0.71 1.00 38 38 1.00 1.00 1.00
Total 352 211 0.60 0.55 0.65 368 300 0.82 0.77 0.86
3. RES ULTS
The results of both dengue serosurveys in the state of Yu-
catan, Mexico in 1996 and 2006, show an overall seropositiv-
ity to Denv infection of 59.94% in 1996 and 81.52% in 2006.
Seropositivity increased by 21.58% in 2006 when compared
to 1996, that represent an annual average increase of 2% for
the ten-year-period. Seropositive by age group and gender
are detailed in Table 1.
While the 0-4-year-age group showed no increase in seropos-
itivity between 1996 and 2006, an increment was observed
in all other age groups, which means that seropositivity in-
creased with age. It is important to mention that a slightly
higher seroprevalence was found in males than females (see
Figure 1).
Figure 1. Overall seropositivity from 1996 and 2006
surveys by gender
A total of 6,443 DF cases in the state of Yucatan were re-
ported to the Epidemiologic Surveillance System between
1996 and 2006 (see Table 2), additionally, 638 Dengue hem-
orrhagic fever cases in Yucatan were also reported in that
period, meaning that Dengue Hemorrhagic fever represented
almost a 1% of all cases. It is important to mention that in
1997, an epidemic year, the proportion of DHF was lower
(0.05) than in non-epidemic years (see Figure 2).
Table 2. Confirmed DF cases between 1996 and 2006 in
Yucatan from epidemiologic surveillance
Year/Age 0-4 5-14 15-24 25-44 45-64 ≥ 65 Total
1996 30 210 195 13 32 45 525
1997 231 1,909 397 996 200 192 3,925
1998 5 17 4 0 0 26 52
1999 12 24 6 0 0 0 42
2000 0 0 0 0 0 0 0
2001 22 99 44 59 7 18 249
2002 51 300 175 171 27 25 749
2003 0 6 4 5 0 4 19
2004 8 17 10 8 1 7 51
2005 6 39 31 277 8 5 366
2006 21 227 102 79 14 22 465
Total 386 2,848 968 1,608 289 344 6,443
4. DISCUSSION
Seropositivity to Denv in Yucatan increased dramatically in
the ten-year-period elapsed between 1996 and 2006. Previ-
ous surveys in Mexico and other Latin American countries
suggest that almost 65% of all infections are asymptomatic,
and when adding the asymptomatic to the undiagnosed clin-
ical cases, it could be estimated that up to 80% of DV in-
fections remain unidentified by epidemiological surveillance
system.[7, 8]
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Figure 2.
Degnue fever and dengue hemorrhagic fever cases
in Yucatan reported between 1996 and 2006
In the present study we showed an increase in the popula-
tion seropositivity between 1996 and 2006. This increase
could not be otherwise estimated by analyzing DF and DHF
reported cases alone, as seropositivity reflects not only symp-
tomatic but also asymptomatic Denv infections. Anyway,
by analyzing serosurveys results alone, retrospectively, we
would not be able to identify the epidemic year of 1997,
for that reason serosurveys and DF, DHF reported cases are
information from different sources that complement each
other, supporting the fact that passive and active surveillance
need both to be implemented in order to have an ampler
perspective of the Denv dynamics in the region.
Epidemiological surveillance of dengue, when developed
by passive surveillance systems, involves that all suspected
dengue cases must be reported and the laboratory confirma-
tion of a proportion of those suspected cases, while active
surveillance is useful to identify subclinical infections in the
population, and it can include periodical serosurveys.[9,10]
Worldwide, national dengue epidemiological surveillance
systems may vary, however, identification of acute cases is a
common strategy; but in some countries, active surveillance
strategies are developed during low transmission season, al-
lowing the comparison of information and estimation of
approximate numbers of incidence and evaluation of control
strategies. In Mexico, serosurveys are not included in the
dengue epidemiologic surveillance system.[10, 11]
According to the World Health Organization, active surveil-
lance can provide an accurate and pertinent warning for
Dengue epidemics that can improve the preventive strategies,
but it is important to use it effectively for planning an effec-
tive response, while passive surveillance systems alone are
ineffective for detecting an epidemic much before peak trans-
mission. If we put the data we analyzed in the present study
as an antecedent of what happened in the years following
the last serosurvey, we can imply that if serosurveys were
developed periodically, and if they included serotype specific
immunity analyses (PRNT) along with vector surveillance,
the Mexican epidemiologic bureau could have been able to
predict early the outbreaks and it could have been able to
plan specific strategies to reduce the burden of dengue in the
region.[12, 13]
Twenty and ten years ago, Yucatan had not reached the actual
levels of urban population density, which has implications
due to the fact that the presence of the vector and the viral
transmission are intensified by the rapid urban growth. Nowa-
days 84% of the state population live in urban areas, that is
why updated serosurveys could be useful to determine the
contemporary population seropositivity for Denv infections
in the region. It is not late for the Mexican health agencies
to improve the dengue surveillance system, including the
implementation of periodic serosurveys in endemic regions
as a part of a complete, holistic approach, in order to not only
predict the occurrence of an outbreak, but also to evaluate
the impact of DF and DHF programs.[14–16]
5. CON CL US IO NS
Data drawn from the 1996 and 2006 serosurveys showed
an increase of seropositivity to Denv infections, which can
partially be explained by the 1997 outbreak in the Yucatan.
While seroprevalence studies were useful to identify the pro-
portion of seropositive population, the case reports from the
epidemiologic surveillance system were useful to identify
the epidemic year, meaning that both sources of information
are complementary to better understand the Denv dynamics
during the ten-year-period elapsed between 1996 and 2006.
Limitation
There are several limitations that need to be considered in
the present study. The main limitation derives from the time
when the information for this study was collected, as it has
passed twenty years since the generation of the first serosur-
vey and ten years since the second serosurvey was developed.
During that time, the population and environmental aspects
related to dengue as a vector borne disease, have changed.
Our data need to be interpreted with caution considering the
time elapsed.
Another aspect to consider is that the epidemiologic surveil-
lance systems have changed with time, and some impreci-
sions could derive from these changes in the report of DF and
DHF cases in the state of Yucatan. Even when diagnostic ca-
pacity and methods for diagnosis have not changed, the case
reports 20 years ago were mostly made in paper formats and
faxed to the epidemiologic surveillance departments in the
city of Mexico to be entered in the national database. With
the widespread access to internet and the National Epidemio-
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logic Surveillance platform, case reports are now uploaded
in real time.
Finally, limitations associated with the laboratory diagnosis
need also to be kept in mind, as only Denv antibodies were
considered to establish seropositivity among individuals and
also to identify DF, DHF cases. Sensitivity and specificity of
IgM and IgG antibodies should be considered along with the
possibility of crossed reactivity to other flaviviruses. Never-
theless, no other flaviviruses circulated in the region for the
previous seven decades (yellow fever occurred in Yucatan
in the early 1920s). Clinical manifestations and migration
antecedents were asked to the participants and correlated
with the laboratory results in all cases.
CON FLI CT S OF INTEREST DISCLOSURE
Authors declare that they have no competing interests.
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