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Saint Louis encephalitis virus, Brazil.

To the Editor: Saint Louis encephalitis virus (SLEV), a member of the Flaviviridae family, is widely dispersed in the Americas (1,2). In Brazil, SLEV was first isolated in the 1960s from a pool of mosquitoes at the Amazon Basin. Subsequently, the virus was repeatedly isolated from animals and arthropods in the Amazon region and Sao Paulo state (3). Nonetheless, isolation of SLEV from humans is rare; only 2 isolates from humans were described before 2005. Each isolate was from a patient who had jaundice and febrile illness without any neurologic symptoms (1,3). Recently in Sao Paulo, SLEV was isolated from a patient who had an incorrect diagnosis of dengue fever (2,4).

Despite the rare isolation of SLEV from humans, antibodies to this virus have been found in [approximately equal to] 5% of studied populations in the north and southeast regions of Brazil. However, because of antibody cross-reactivity among different flaviviruses and the fact that this population is vaccinated against yellow fever and exposed to dengue virus (DENV), such results should be interpreted carefully. Nevertheless, in these areas, SLEV may circulate and infect humans, although most infections are undiagnosed (1,3,5).

In contrast to previous instances in which the disease was detected in only 1 patient, we describe the first community outbreak of SLEV in Brazil. The outbreak was detected in Sao Jose do Rio Preto (population 400,000), in northwest Sao Paulo state. This outbreak was concurrent with a large outbreak of DENV serotype 3 (DENV-3), which occurred during the first half of 2006, with >15,000 possible cases reported to public health authorities. During this time, we were involved in an epidemiologic study to monitor the disease. We tested [approximately equal to] 250 samples for DENV, and 65% were positive. We tested for SLEV only those patients who were in our hospital or those who were referred to us for SLEV testing after an initial diagnosis of SLEV or DENV. The protocol approved by our ethical committee allowed us to test only samples from these patients (process no. 300/2004).

We used a multiplex nested reverse transcription--PCR (RT-PCR) assay to identify the most common flaviviruses in Brazil (DENV-1, DENV-2, DENV-3, yellow fever virus) as well as DENV-4, Ilheus virus, Iguape virus, Rocio virus, and SLEV. Of 54 samples (49 serum and 5 cerebrospinal fluid [CSF]) that were negative for DENV and yellow fever virus, SLEV RNA was detected in 6 (4 serum and 2 CSF) (6). RT-PCR results were negative for all other tested flaviviruses. Sequences of the amplified SLEV cDNAs from the 2 CSF samples were determined by using an ABI377 automated sequencer (Applied Biosystems, Foster City, CA, USA). The resulting sequences (GenBank accession nos. DQ836336 and DQ836337) were identical and showed 96% homology to an Argentinean SLEV isolate (AY6-32544). All 6 SLEV-infected patients had an initial diagnosis of dengue fever or viral encephalitis; 3 had a diagnosis of viral meningoencephalitis, and the other 3 had signs of hemorrhagic disease (Table).

Dengue is widely disseminated in Brazil and causes large outbreaks almost every year. The high prevalence of antibodies in the Brazilian population (1,3,6) suggests that SLEV infections are being misdiagnosed; its importance is underestimated. Brazil has no SLEV surveillance programs, and health professionals do not usually consider SLEV among their differential diagnoses. This SLEV outbreak was detected in a large urban center and was not specifically linked to patients who dwell in pockets of tropical forests, as previously reported (1-4).

This outbreak may represent the first time that hemorrhagic signs have been linked to SLEV infections. SLEV-associated hemorrhagic manifestations have not been reported in the literature. However, of our 6 SLEV-infected patients, 3 had hemorrhagic signs. Substantiating a causal link between SLEV infection and such clinical manifestations is difficult because DENV is endemic in the studied region (7). Possibly, SLEV-infected patients with hemorrhagic signs may have been previously infected by DENV. No reports have linked hemorrhagic manifestations to sequential DENV and SLEV infections; this possible link needs to be carefully evaluated.

In Argentina, SLEV has been isolated several times from animals (8). In some regions, SLEV seroprevalence in humans is [approximately equal to]13% (9), but the number of documented human infections is small (10). These findings indicate either that SLEV is more prevalent than reported or that SLEV is reemerging. The Brazilian cases may parallel the situation in Argentina.

Our results clearly indicate an SLEV outbreak among this local population in Brazil. This outbreak differs from isolated infections previously described and indicates that this disease may be more prevalent in Brazil. In fact, the number of samples tested for SLEV during this DENV outbreak was relatively small. Had more samples been investigated, more cases of SLEV infection might have been found. A more comprehensive epidemiologic study is required to fully assess the magnitude of SLEV infection in Brazil.

This work was supported by grants from Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (0401396/2004-5) to M.L.N. and Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) (04/11098-2, 06/0170-9, and 03/03682-3) to M.L.N., F.C.N., and L.T.M.F., respectively. R.V.M.B. and I.L.S.C. received fellowships from FAPE-SP (grants 05/03260-7 and 06/00179-7). This work was supported by the Viral Diversity Genetic Network (VGDN-FAPESP-Brazil).


(1.) Figueiredo LT. The Brazilian flaviviruses. Microbes Infect. 2000;2:1643-9.

(2.) Rocco IM, Santos CL, Bisordi I, Petrella SM, Pereira LE, Souza RP, et al. St. Louis encephalitis virus: first isolation from a human in Sao Paulo state, Brazil. Rev Inst Med Trop Sao Paulo. 2005;47:281-5.

(3.) Vasconcelos PFC, Travassos da Rosa APA, Pinheiro FP, Shope RE, Travassos da Rosa JFS, Rodrigues SG, et al. Arboviruses pathogenic from man in Brazil. In: Travassos da Rosa APA, Vasconcelos PFC, Travassos da Rosa, JFS, editors. An overview of arbovirology in Brazil and neighboring countries. Belem (Brazil): Instituto Evandro Chagas; 1998. p. 72-99.

(4.) Santos CL, Sallum MA, Franco HM, Oshiro FM, Rocco IM. Genetic characterization of St. Louis encephalitis virus isolated from human in Sao Paulo, Brazil. Mem Inst Oswaldo Cruz. 2006;101:57-63.

(5.) de Sousa Lopes O, de Abreu Sacchetta L, Coimbra TL, Pereira LE. Isolation of St. Louis encephalitis virus in South Brazil. Am J Trop Med Hyg. 1979;28:583-5.

(6.) de Morals Bronzoni RV, Baleotti FG, Ribierra Nogueira MR, Nunes M, Moraes Figueiredo LT. Duplex reverse transcription-PCR followed by nested PCR assays for detection and identification of Brazilian alphaviruses and flaviviruses. J Clin Microbiol. 2005;43:696-702.

(7.) Mondini A, Chiaravalloti-Neto F, Galloy-Sanches M, Lopes JCC. Spatial analysis of dengue transmission in a medium-sized city in Brazil. Rev Saude Publica. 2005;39: 444-51.

(8.) Sabattini MS, Aviles G, Monath TO. Historical, epidemiological and ecological aspects of arbovirus in Argentina: Flaviviridae, Bunyaviridae and Rhabdoviridae. In: Travassos da Rosa APA, Vasconcelos PFC, Travassos da Rosa JFS, editors. An overview of arbovirology in Brazil and neighbouring countries. Belem (Brazil): Instituto Evandro Chagas; 1998. p. 113-134.

(9.) Spinsanti LI, Re VE, Diaz MP, Contigiani MS. Age-related seroprevalence study for St. Louis encephalitis in a population from Cordoba, Argentina. Rev Inst Med Trop Sao Paulo. 2002;44:59-62.

(10.)Spinsanti L, Basquiera AL, Bulacio S, Somale V, Kim SC, Re V, et al. St. Louis encephalitis in Argentina: the first case reported in the last seventeen years. Emerg Infect Dis. 2003;9:271-3.

Adriano Mondini, * (1) Izabela Lidia Soares Cardeal,* (1) Eduardo Lazaro, ([dagger]) Silva H. Nunes, * Cibele C. Moreira, * Paula Rahal, ([double dagger]) Irineu L Maia, * ([section]) Celia Franco,* ([section]) Delzi V. N. Gongora, * ([section]) Fernando Gongora-Rubio, * ([section]) Eliana Marcia Sotello Cabrera, * ([section]) Luiz Tadeu Moraes Figueiredo, ([paragraph]) Flavio Guimaraes da Fonseca, # Roberta Vieira Moraes Bronzoni, * Franscisco Chiaravalloti-Neto, * and Mauricio Lacerda Nogueira * ([section])

* Faculdade de Medicina de Sao Jose do Rio Preto, Sao Jose do Rio Preto, Sao Paulo, Brazil; ([dagger]) Secrataria Municipal de Sa0de, Sao Jose do Rio Preto, Sao Paulo, Brazil; ([double dagger]) Universidade Estadual Paulista, Sao Jose do Rio Preto, Sao Paulo, Brazil; ([section]) Hospital de Base de Sao Jose do Rio Preto, Sao Paulo, Brazil; ([paragraph]) Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil; and # Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

(1) These authors contributed equally to this work.

Address for correspondence: Mauricio Lacerda Nogueira, Laboratorio de Pesquisas em Virologia, Departamento de Doencas lnfecciosas e Parasitairias, Faculdade de Medicina de Sao Jose do Rio Preto, FAMERP, Av. Brigadeiro Faria Lima 5416, Sao Jose do Rio Preto, SP, Brazil 15090-000; email:
Table. Clinical data, 6 patients with Saint Louis encephalitis, Brazil,
2006 *

 Sample Date of
Patient tested by hospital Initial diagnosis
no. (age) RT-PCR admission at admission

1 (27 y) Serum Feb 25 Dengue fever
2 (7 mo) Serum Mar 06 Dengue hemorrhagic fever,
 viral encephalitis
3 (37 y) Serum Apr 22 Dengue hemorrhagic fever
4 (34 y) Serum Apr 23 Dengue hemorrhagic fever
5 (5 y) CSF Jun 05 Viral meningoencephalitis
6 (11 y) CSF Jun 07 Viral meningoencephalitis

Patient Signs, symptoms,
no. (age) selected laboratory results

1 (27 y) Clinical: fever, abdominal pain, diarrhea
 Serum: AST 58 IU/mL, ALT 69 IU/mL
2 (7 mo) Clinical: fever, abdominal pain, melena,
 petechiae, positive tourniquet test
 Serum: platelets 311,000/[mm.sup.3], hematocrit 29%
 CSF: 13 cells/[mm.sup.3], lymphocytes 86%,
 monocytes 14%
3 (37 y) Clinical: fever, headache, chills, myalgia,
 maculopapular rash, positive tourniquet test
 Serum: hematocrit 43%, platelets 280,000/[mm.sup.3]
 History: previous DENY infection (2002)
4 (34 y) Clinical: fever, headache, chills, myalgia,
 maculopapular rash, positive tourniquet test
 Serum: platelets 141 ,000/[mm.sup.3], hematocrit 38%,
 AST 81 IU/mL, ALT 56 IU/mL
5 (5 y) Clinical: fever
 CSF: 286 cells/[mm.sup.3], lymphocytes 60%,
 polymorphonuclear cells 37%, eosinophils 3%
6 (11 y) Clinical: fever, facial palsy
 CSF: 12 cells/[mm.sup.3], lymphocytes 100%

* RT-PCR, reverse transcription-PCR; AST, aspartate aminotransferase;
ALT, alanine aminotransferase; CSF, cerebrospinal fluid; DENY, dengue
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Title Annotation:LETTERS
Author:Nogueira, Mauricio Lacerda
Publication:Emerging Infectious Diseases
Article Type:Letter to the editor
Geographic Code:3BRAZ
Date:Jan 1, 2007
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