Dengue Viruses in Brazil
by
Rita Maria Ribeiro Nogueira*#, Marize Pereira Miagostovich*
and Hermann Gonçalves Schatzmayr**
*Laboratory of Flavivirus, Instituto Oswaldo Cruz/FIOCRUZ, Avenida Brasil 4365,
21040-190, Rio de Janeiro, RJ, Brasil
**Department of Virology, Instituto Oswaldo Cruz/FIOCRUZ, Avenida Brasil 4365,
21040-190, Rio de Janeiro, RJ, Brasil
Abstract
Dengue was first recognized in Brazil in 1981-1982. However, the disease became a nationwide public
health problem after epidemics occurred in the state of Rio de Janeiro which were caused by DEN-1 and
DEN-2 in 1986 and 1990, respectively. Widespread circulation of viruses in the entire country resulted
in about 75% of dengue cases notified in the Americas in the last 8 years, with an increased incidence of
DHF/DSS. All Brazilian regions have been affected by the epidemics. However, the North-East and
South-East have a higher number of notifications.
The more recent introduction of DEN-3 in the state of Rio de Janeiro resulted in the emergence of the
largest epidemic with more than 220,000 notified cases of dengue between January-May 2002. The cocirculation of three dengue serotypes has been responsible for the increase in the severe forms of the
disease i.e. DHF/DSS.
Keywords: Dengue/Dengue haemorrhagic fever spread, public health problem, epidemics, multivirus circulation,
Brazil.
Introduction
The high level of dengue virus activity in the
American continent and the reinfestation of
Brazil by Aedes aegypti in 1977 contributed
to the reintroduction of the dengue (DEN)
viruses into Brazil in the 80s(1,2). From that
decade onwards, the country has been
responsible for more than 75% of the
reported cases of dengue in the Americas
(Figure 1).
A dengue outbreak due to DEN-1 and
DEN-4 viruses (1981-1982) occurred in the
city of Boa Vista, state of Roraima in the
Amazon region(3). This episode was
controlled by local measures of vector
elimination and no dengue activity was
notified during the following four years in
the country. It was only in 1986 with the
introduction of the DEN-1 virus into the
state of Rio de Janeiro that dengue became a
nationwide public health problem(4).
# For correspondence: [email protected]
Dengue Bulletin – Vol 26, 2002
77
Dengue Viruses in Brazil
Figure 1: Dengue reported cases in the Americas and Brazil
900000
800000
Number of cases
700000
600000
500000
400000
300000
200000
100000
0
1995
Brazil
1996
1997
Americas
1998
1999
2000
2001
2002
Years
Source: Americas data from www.paho.org
Source of Brazilian data: National Centre for Epidemiology, Ministry of Health Brazil until 31st epidemiological week
Difficulties in implementing an effective
vector control programme resulted in the
rapid spread of the virus and consequent
occurrence of epidemics in several states.
The situation was aggravated in 1990 by the
introduction of the DEN-2 virus into the
state of Rio de Janeiro(5) and its subsequent
spread to other regions in the country. By
2001, 25 of the 27 Brazilian states had
reported dengue epidemics, with a total of 3
million cases, resulting from DEN-1 and
DEN-2 epidemics in the last 16 years(6).
After complete absence from the
Americas for almost 15 years, the DEN-3
virus was reintroduced into the continent in
1994(7), reaching Brazil in 2000 and causing
a large and severe dengue epidemic in the
summer of 2001-2002(8,9). The state of Rio
de Janeiro again proved to be the nodal state
78
for the introduction and dissemination of
this new serotype in the country.
Dengue in the state of
Rio de Janeiro
The dengue infection was first confirmed by
our laboratory in April 1986, when the DEN1 virus was isolated from the blood of 8
cases (8/8), collected during an epidemic in
the municipality of Nova Iguaçu(10). This
municipality belongs to the Greater
Metropolitan Area of the state, which
includes the capital, Rio de Janeiro, and 20
other municipalities, with 11,151,639
inhabitants out of the 14,768,969
inhabitants in the whole state. This heavy
circulation of people in the region facilitated
the rapid spread of dengue virus, causing an
explosive epidemic, with 92,000 cases
reported during the 1986-1987 period(11).
Dengue Bulletin – Vol 26, 2002
Dengue Viruses in Brazil
An active surveillance programme by
the Health Secretary of Niterói (Greater
Metropolitan Area) resulted in the early
identification of DEN-2 by April 1990,
exactly four years after the DEN-1 virus
isolation and during a period of high DEN-1
virus activity. During the epidemic in 19901991, which presented two waves, a
significantly greater proportion of patients
with thrombocytopenia and requiring
hospitalization were seen in the DEN-2
predominant phase(5).
Both the DEN-1 and DEN-2 viruses
were isolated during a new epidemic
recognized in 1995-1996, with a total of
51,465 reported cases of dengue fever. In
January 1998, a new epidemic broke out in
the Paraíba river valley and quickly spread to
other municipalities in the state reaching an
important tourist area on the northern coast
of the state(11).
During 2000, a Virological Surveillance
Programme was carried out in Nova Iguaçu
during an inter-epidemic period. This
resulted in the isolation of the DEN-3 virus
from a case with classical dengue fever and
from the vector Aedes aegypti collected in
the field(8,12). The introduction of the DEN-3
virus increased the number of notified cases
to 69,269 in 2001 and during the summer of
2002, caused the most severe epidemic in
the state of Rio de Janeiro so far observed(9).
The number of reported cases exceeded the
epidemic of 1990-1991 in which more than
100,000 cases, with 462 cases of dengue
haemorrhagic fever/dengue shock syndrome
(DHF/DSS) and 8 deaths were reported. In
2002, until the 21st epidemiological week, a
total of 224,684 cases had already been
reported with 1,728 cases of DHF/DSS and
61 confirmed deaths. The higher notification
of the disease was observed in the Greater
Metropolitan Area which has been the most
heavily affected area with respect to dengue
outbreaks (Figure 2).
Figure 2: Dengue reported cases in the state of Rio de Janeiro and
the Greater Metropolitan Area
100000
State of Rio de Janeiro
Greater Metropolitan Area
90000
80000
NUMBER OF CASES
70000
60000
50000
40000
30000
20000
10000
0
1986
1987
1988
1989
1990
Source: SES-RJ/SUS/CE/ADTVZ
Dengue Bulletin – Vol 26, 2002
1991
1992
1993
1994
YEARS
1995
1996
1997
1998
1999
2000
2001
2002
*Until 21 st epidemiological week
79
Dengue Viruses in Brazil
Laboratory studies carried out on
1,478 suspected dengue cases in the same
period confirmed a 54.5% infection rate
by serology and/or virus isolation and
reverse transcriptase-polymerase chain
reaction (RT-PCR). Three DEN-1, one
DEN-2 and 320 DEN-3 virus strains were
detected, showing that this new serotype
represented 98.7% of the circulating
viruses during the 2002 epidemic in the
state. Forty fatal cases were confirmed in
the laboratory, 20 of them were shown to
be positive by at least two different
methodologies, and the DEN-3 virus was
the only serotype detected in these cases.
DEN-1, DEN-2 and DEN-3
spread to Brazilian states
The South-East and the North-East are the
most affected regions by dengue
infections, with epidemics occurring
almost yearly. In the South-East region
besides the state of Rio de Janeiro, the
states of Minas Gerais and Espírito Santo
have also been reporting epidemics in
both the capital cities and inland
municipalities. In the state of São Paulo,
dengue viruses activity is mainly observed
in inland municipalities and sporadically in
coastal localities. The North-eastern
region, which is composed of nine states,
has suffered successive dengue epidemics
and it has been responsible for the highest
number of dengue notifications during the
later 90s(13,14,15,16,17).
The Midwest region, which includes
the Federal District, confirmed DEN-1
virus circulation in 1990. In 1995, DEN-2
virus was isolated and one case with dual
infection was reported(6,18).
80
In 1991, a dengue epidemic caused
by the DEN-2 virus occurred in the state of
Tocantins(19) and in 1995 in the state of
Pará(20), both in the Northern region. The
state of Roraima confirmed dengue activity
in 1996, 14 years after the first outbreak
occurred in the state. In 1998, the state of
Amazonas notified a dengue epidemic
with 23,910 cases. In 2001 all states in
that region, including Acre and Amapá,
were affected by epidemics of variable
magnitude(6).
In the Southern region, the state of
Parana had been the only one notifying
dengue since 1995. No indigenous cases
had been notified so far by the states of
Santa Catarina and Rio Grande do Sul(6).
Figure 3 shows the distribution of
dengue reported cases, according to the
Brazilian regions. It should be pointed out
that dengue infections in the country,
according to the available epidemiological
data, are in general found in all age
groups.
Figure 3: Incidence rate (/100,000
inhabitants) of notified cases of dengue fever
by year of occurrence, Brazil and regions,
1986-2002*
North
188,634
cases
Midwest
208,709
cases
North-east
1,364,731
cases
South-east
1,261,018
cases
South
29,510 cases
Dengue Bulletin – Vol 26, 2002
Dengue Viruses in Brazil
Table: Number of DHF/DSS and deaths reported in Brazil, 1990-2001
DHF
Deaths
1990
1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001
274
188
–
–
25
114
69
46
105
72
40
679
–
–
–
11
2
1
9
10
3
3
29
8
Source: National Center of Epidemiology, Ministry of Health, Brazil
–= indicates no notified DHF/DSS and deaths
The co-circulation of DEN-1 and DEN2 viruses in Brazil led to the appearance of
DHF/DSS (Table), initially in Rio de Janeiro
and afterwards in other states(5,21,22,23). The
increase in the number of more severe cases
in the country, like in many others in the
Americas, was coincidental with the
introduction of the DEN-2 south-east Asian
genotype into the continent(24).
Unusual manifestations such as the
involvement of the central nervous system
were first reported during the 1986-1987
epidemic in Rio de Janeiro and later in
different states, including one case in the
state of Rio Grande do Norte, where
immunohistochemistry detected dengue
antigen in neurons(32,33,34,35).
Analysis by the sequencing of the
genome, performed on DEN-1 and DEN-2
viruses isolated in Brazil, identified the
Caribbean and the south-east Asian
genotypes for the DEN-1 and DEN-2 viruses,
respectively(25,26,27,28). The partial sequence of
the junction from E/NS1 of DEN-2 Brazilian
isolates, during 1990 to 2001, showed that
this genotype is still the only one circulating
in Brazil (data not published).
High levels of serum amino-transferases
have also been observed. In the more severe
cases, yellow fever infections were
occasionally
suspected;
however,
epidemiological investigations and laboratory
results confirmed dengue infection in all
these cases.
The DEN-3 virus genotype introduced
into the continent has been associated with
major DHF/DSS epidemics in Sri Lanka and
India and with DHF/DSS cases and deaths in
Mexico and Central American countries(29,30).
The molecular characterization of DEN-3
viruses isolated from autochthonous cases in
Rio de Janeiro, by the sequencing of
structural proteins, showed that our strain
belonged to the same genotype(31).
Dengue Bulletin – Vol 26, 2002
During the DEN-3 epidemic in Rio de
Janeiro, we were able to detect by RT-PCR,
viral RNA in cerebrospinal fluid, liver, brain,
lung, spleen, and kidney from fatal cases.
In summary, the dengue viruses activity
in Brazil during the past 16 years is
demonstrated by the high number of
notified cases and the number of states
involved in the epidemics. The high dengue
endemicity besides the co-circulation of
three serotypes have been responsible for
the increase of the severe forms of the
disease such as DHF/DSS in the country.
81
Dengue Viruses in Brazil
Acknowledgments
The authors thank CNPq, FIOCRUZ,
CGELAB /CENEPI- Ministry of Health, Brazil,
for financial support. To Dr Gualberto
Teixeira dos Santos Jr., Paulo Roberto de
Almeida Barbos, Sérgio Ferreira Romariz,
Yolanda Bravin and Ângela Cristina Veltri,
Secretary of Health of the state of Rio de
Janeiro, for providing epidemiological data.
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