Dengue Viruses in Brazil

Transcription

1 by Rita Maria Ribeiro Nogueira*#, Marize Pereira Miagostovich* and Hermann Gonçalves Schatzmayr** *Laboratory of Flavivirus, Instituto Oswaldo Cruz/FIOCRUZ, Avenida Brasil 4365, , Rio de Janeiro, RJ, Brasil **Department of Virology, Instituto Oswaldo Cruz/FIOCRUZ, Avenida Brasil 4365, , Rio de Janeiro, RJ, Brasil Abstract Dengue was first recognized in Brazil in 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 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 of dengue between January-May 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 of dengue in the Americas (Figure 1). A dengue outbreak due to DEN-1 and DEN-4 viruses ( ) 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: rita@ioc.fiocruz.br Dengue Bulletin Vol 26,

2 Figure 1: Dengue reported in the Americas and Brazil Number of Brazil Americas Years Source: Americas data from Source of Brazilian data: National Centre for Epidemiology, Ministry of Health Brazil until 31 st 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, 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 (8,9). The state of Rio de Janeiro again proved to be the nodal state 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 DEN- 1 virus was isolated from the blood of 8 (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 reported during the period (11). 78 Dengue Bulletin Vol 26, 2002

3 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 , 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 , with a total of 51,465 reported 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 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 exceeded the epidemic of in which more than 100,000, with 462 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 had already been reported with 1,728 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 in the state of Rio de Janeiro and the Greater Metropolitan Area State of Rio de Janeiro Greater Metropolitan Area NUMBER OF CASES Source : SES - RJ/SUS/CE/ADTVZ YEARS *Until21 st epidemiological week Dengue Bulletin Vol 26,

4 Laboratory studies carried out on 1,478 suspected dengue 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 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. 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 In 1995, DEN-2 virus was isolated and one case with dual infection was reported (6,18). 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. 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 No indigenous 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, 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 of dengue fever by year of occurrence, Brazil and regions, * North 188,634 Midwest 208,709 North-east 1,364,731 South-east 1,261,018 South 29, Dengue Bulletin Vol 26, 2002

5 Table: Number of DHF/DSS and deaths reported in Brazil, DHF Deaths Source: National Center of Epidemiology, Ministry of Health, Brazil = indicates no notified DHF/DSS and deaths The co-circulation of DEN-1 and DEN- 2 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 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). 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). 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 and deaths in Mexico and Central American countries (29,30). The molecular characterization of DEN-3 viruses isolated from autochthonous in Rio de Janeiro, by the sequencing of structural proteins, showed that our strain belonged to the same genotype (31). Unusual manifestations such as the involvement of the central nervous system were first reported during the 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). High levels of serum amino-transferases have also been observed. In the more severe, yellow fever infections were occasionally suspected; however, epidemiological investigations and laboratory results confirmed dengue infection in all these. 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. In summary, the dengue viruses activity in Brazil during the past 16 years is demonstrated by the high number of notified 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. Dengue Bulletin Vol 26,

6 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. References 1. Pinheiro FP and Corber SJ. Global situation of dengue and dengue hemorrhagic fever and its emergence in the Americas. World Health statistics quarterly, 1997, 50: Gubler DJ. Dengue/Dengue Hemorrhagic fever in the Americas: prospects for the year In Dengue, a Worldwide Problem, a common Strategy Eds: SB Halstead and H Gomez-Dantes Mexico City, 1992: Osanai CH, Travassos Da Rosa APA and Tang AT. Surto de dengue em Boa Vista em Roraima. Revista do Instituto de Medicina Tropical de São Paulo, 1993, 25: Schatzmayr HG, Nogueira RMR and Travassos da Rosa APA. An outbreak of dengue virus at Rio de Janeiro. Memorias do Instituto Oswaldo Cruz, 1986, 81: Nogueira RMR, Miagostovich MP, Lampe E, Souza RW, Zagne SMO and Schatzmayr HG. Dengue epidemic in the State of Rio de Janeiro, Brazil, : co-circulation of dengue 1 and dengue 2 serotypes. Epidemiology and Infection, 1993, 111: Ministério da Saúde, Brasil. Dengue: Total de casos notificados por mês e por unidade federada, Brasil. 7. Anonymous. Dengue 3 In Central America. Dengue Surveillance. Summary. Dengue Branch, San Juan, Puerto Rico. Division of Vector-Borne Infectious Diseases, CDC, 1995, 70: Nogueira RMR, Miagostovich MP, Filippis AMB, Pereira MAS and Schatzmayr HG. Dengue virus type 3 in Rio de Janeiro, Brazil. Memórias do Instituto Oswaldo Cruz, 2001, 96(7): Secretaria de Estado de Saúde do Rio de Janeiro (SES/RJ). Boletim n. 22. Casos suspeitos notificados de dengue/estado do Rio de Janeiro. 10. Miagostovich MP, Nogueira RMR, Cavalcante SMB, Marzochi KBF and Schatzmayr HG. Dengue epidemic in the State of Rio de Janeiro, Brazil: Virological and epidemiological aspects. Revista do Instituto de Medicina Tropical de São Paulo, 1993, 35 (2): Nogueira RMR, Miagostovich MP, Schatzmayr HG, Araújo ESM, Santos FB, Filippis AMB, Souza RW, Zagne SMO, Nicolai C, Baran M and Teixeira Filho G. Dengue in the State of Rio de Janeiro, Brazil, Memórias do Instituto Oswaldo Cruz, 1999, 94(3): Lourenço de Oliveira R, Honório NA, Castro MG, Schatzmayr HG, Miagostovich MP, Alves JCR, Silva WC, Leite PJ and Nogueira RMR. Dengue Virus Type 3 (DEN-3) Isolation from Aedes aegypti in the municipality of Nova Iguaçú, State of Rio de Janeiro, 97, in press. 13. Nogueira RMR, Miagostovich MP, Schatzmayr HG, Morais G, Cardoso FMA, Ferreira J, Cerqueira V and Pereira M. Dengue type 2 outbreak in the south of the state of Bahia, Brazil: Laboratorial and epidemiological studies. Revista do Instituto de Medicina Tropical de São Paulo, 1995, 37 (6): Cunha RV, Miagostovich MP, Petrola Z, Araújo ESM, Cortez D, Pombo V, Souza RV, Nogueira RMR and Schatzmayr HG. Retrospective study on dengue in Fortaleza, State of Ceará. Memórias do Instituto Oswaldo Cruz, Rio de Janeiro, March- April 1998, 93: Cunha RV, Schatzmayr HG, Miagostovich MP, Barbosa AMA, Paiva FGP, Miranda RMO, Ramos CCF, Coelho JCO, Santos FB and Nogueira RMR. Dengue epidemic in the State of Rio Grande do Norte, Brazil, in Transaction Royal Society Tropical Medical Hygiene, 1999, 93: Cordeiro, MT. Dengue in the State of Pernambuco, Brazil: Virological, clinical and epidemiological aspects. Virus Reviews & Research, 1997, 2 (1-2): Figueiredo LTM. Dengue in Brazil I: history, epidemiology and research. Virus Review and Research, 1996, 1-2: Dengue Bulletin Vol 26, 2002

7 18. Rocco IM, Barbosa ML and Kanomata EHN. Simultaneous infection with dengue 1 and 2 in a Brazilian patient. Revista do Instituto de Medicina Tropical São Paulo, 1998, 40: Vasconcelos PFC, Travassos da Rosa ES and Travassos da Rosa. Epidemia de febre clássica de dengue causada pelo sorotipo 2 em Araguaina, Tocantins, Brasil. Revista do Instituto Medicina Tropical de São Paulo, 1993, 35: Travassos da Rosa APA, Vasconcelos PFC, Travassos da Rosa ES, Rodrigues SG, Mondet B, Cruz ACR, Sousa MR and Travassos da Rosa JFS. Dengue epidemic in Belém, Pará, Brazil, Emerging Infectious Diseases, 2000, 6(3): Zagne SMO, Alves VGF, Nogueira RMR, Miagostovich MP, Lampe E and Tavares W. Dengue haemorrhagic fever in the state of Rio de Janeiro, Brazil: a study of 56 confirmed. Transaction Royal Society of Tropical Medicine and Hygiene, 1994, 88: Souza RW, Cunha RV, Miagostovich MP, Timbó MJ, Montenegro F, Pessoa ETFP, Nogueira RMR and Schatzmayr HG. An outbreak of dengue virus infection in the state of Ceará, Brazil. Memórias do Instituto Oswaldo Cruz, 1995, 90 (3): Vasconcelos PF, Menezes DB, Melo LP, Paula Pessoa ETF, Rodrigues SG, Travassos da Rosa ES, Timbó MJ, Coelho ICB., Montenegro F, Travassos da Rosa JFS, Andrade FMO and Travassos da Rosa APA. A large epidemic of dengue fever with dengue hemorrhagic in Ceará State, Brazil, Revista do Instituto de Medicina Tropical de São Paulo, 1994, 37: Rico-Hesse R, L M Harrison, R Alba Salas, D Tovar, A Nisalak, C Ramos, J Boshell, MTR De Mesa, RMR Nogueira and A Travassos Da Rosa. Origins of dengue type 2 viruses associated with increased pathogenicity in the Americas. Virology, 1997, 230: Rico-Hesse R. Molecular evolution and distribution of dengue viruses type 1 and 2 in nature. Virology, 1990, 174: Deubel V, Nogueira RMR, Drouet MT, Zeller M, Reynes J and Ma DQ. Direct sequencing of genomic cdna fragment amplified by the polymerase chain reaction for molecular epidemiology of dengue 2 viruses. Archives of Virology, 1993, 129: Miagostovich MP, Nogueira RMR, Schatzmayr HG and Lanciotti RS. Molecular epidemiology of DEN- 2 in Brazil. Memórias do Instituto Oswaldo Cruz, 1998, 93: Santos FB, Miagostovich MP, Nogueira RMR, Schatzmayr HG, Riley LW and Harris E. Complete nucleotide sequence analysis of a Brazilian dengue type 2 virus strain (BR64022/98). Memórias do Instituto Oswaldo Cruz, in press. 29. Lanciotti RS, Lewis JG, Gubler DJ and Trent DW. Molecular evolution and epidemiology of dengue-3 viruses. Journal General Virology, 1994, 77: Figueroa R and Ramos C. Dengue virus (serotype 3) circulation in endemic countries and its reappearance in America. Archives of Medical Research, 2000, 31: Miagostovich MP, dos Santos FB, De Simone TS, Costa EV, Filippis AMB, Schatzmayr HG and Nogueira RMR. Molecular characterization of Dengue Viruses Type 3 isolated in the State of Rio de Janeiro, Brazilian Journal of Medical and Research, in press. 32. Chimelli L, Dumas Hahn M, Barreto Neto M, Grandelle Ramos, Dias M and Gray F. Dengue: neuropathological findings in 5 fatal from Brazil. Clinical Neuropathology, 1990, 9 (3): Vasconcelos PFC, Travassos da Rosa APA, Coelho ICB, Menezes DB, Travassos da Rosa EST, Rodrigues SG and Travassos da Rosa JFST. Involvement of the central nervous system in dengue fever: three serologically confirmed from Fortaleza, Ceará. Revista do Instituto de Medicina Tropical de São Paulo, January-February 1998, 40 (1): Miagostovich MP, Ramos RG, Nicol AF, Nogueira RMR, Cuzzi-Maya T, Oliveira AV, Marchevsky RS, Mesquita RP and Schatzmayr HG. Retrospective study on dengue fatal. Clinical Neuropathathology, 1997, 16: Nogueira, RMR, Filippis AMB, Coelho JMO, Sequeira PC, Schatzmayr, HG, Paiva FG, Ramos AMO and Miagostovich MP. Dengue Virus Infection of the Central Nervous System (CNS): A case report from Brazil. South-East Asian Journal Tropical of Medicine and Public Health, in press. Dengue Bulletin Vol 26,