St. Louis encephalitis in Argentina: the first case reported in the last seventeen years. (Letters).

To the Editor: St. Louis encephalitis is a mosquito-borne viral disease that affects humans. The causative agent, SLEV (formal name: Saint Louis encephalitis virus), is a member of the Flaviviridae family. Severity of the clinical syndromes increases with age, and persons >60 years old have the highest frequency of encephalitis. The primary transmission cycle involves wild passeriform and columbiform birds, and Culex sp. mosquitoes (1). In Argentina, an urban cycle may involve Cx. quinquefasciatus, which is a source of a viral isolate, and abundant birds (house sparrows, doves, or chickens) (2). The distribution of SLEV in Argentina is wide; seroprevalence ranges from 3% to 50% of the country's population (3). Spinsanti et al. reported results of a serologic screening in persons ages 0-87 years who live in the city of Cordoba; antibodies were most frequently found in persons >60 years of age (4). However, cases of St. Louis encephalitis reported in Argentina are very rare. Two cases with serologic diagnosis were reported in 1964 and 1968, respectively (2). In 1971, two more cases were diagnosed on the basis of viral isolation (5). Finally, the last case reported was a patient with meningoencephalitis diagnosed in the province of Buenos Aires by hemagglutination inhibition assay (6). Herein, we report a case of Saint Louis encephalitis that occurred in the province of Cordoba, Argentina.

A 61-year-old man was admitted to the hospital in February 2002, complaining of headache, fever, and diplopia. He had been well until 3 months before admission, when ophthalmic herpes zoster was diagnosed. He underwent therapy with oral acyclovir and had a good clinical outcome. Ten days before admission, he developed unstable gait with misbalance and hand tremors, mainly at his left side. On admission, he had occipital headache, diplopia, and nausea and vomiting associated with high fever and chills. Somnolence appeared a few hours before the consultation.

The patient was a right-handed businessman, a native of Cordoba. He was married and had no risk factors for sexually transmitted diseases. He had not traveled inside or outside the country during the last year. He lived near a river with a high-density population of mosquitoes.

Vital signs on admission showed axillary temperature of 39[degrees]C, pulse of 90 beats per minute, respiratory frequency of 20 per minute, and blood pressure of 110/70 mmHg. Physical examination demonstrated a somnolent patient who was easily aroused and oriented. His speech was slurred. Results of a fundoscopic examination appeared normal. Results of a cranialnerve examination showed horizontal left diplopia with left sixth nerve paresia. A resting, postural, and intentional hand tremor was evident. Motor strength was 5/5 throughout with normal bulk and tone, tendon reflexes, and coordination. Examination of sensitivity showed no abnormalities. A slight neck rigidity was detected.

Routine laboratory analysis was unremarkable, and results of serologic tests for coxsackie virus, echovirus, and HIV were negative. HIV-1 RNA by polymerase chain reaction (PCR) and p24 antigen were also negative. Cerebrospinal fluid study revealed a leukocyte count of 18/[mm.sup.3] (80% lymphocytes), a glucose level of 48 mg/ dL, and a protein level of 87 mg/dL. Cryptococcal antigen, antibodies for syphilis, Human herpesvirus 1 and 2, and PCR for varicella-zoster virus 1 and Human herpesvirus were also negative. Results of an electroencephalogram and a chest radiograph were normal. Therapy with intravenous acyclovir was initiated. A magnetic resonance imaging (MRI) scan of the brain showed a striking signal change on T2 in the substantia nigra of the midbrain, mainly at the right side.

The patient continued febrile, diplopia disappeared, and meningeal signs progressed with frank cervical stiffness, positive Kerning sign, and photophobia. Diffuse tremulousness and axial rigidity appeared. Upper extremities showed rigidity with cogwheel phenomenon. Conversely, lower extremities showed spasticity with bilateral Babinski sign. Tendon reflexes became enhanced. His gait showed retropulsion with wide base sustentation. Dysdiadochokinesia appeared. On the third day, a new lumbar puncture showed worse results: a leukocyte count of 210/[mm.sup.3] (82% lymphocytes), a glucose level of 51 mg/ dL, and a protein level of 106 mg/dL. Another electroencephalographic examination showed unspecific centroparietal disorganization with right side predominance. Intravenous acyclovir was stopped. On the 5th day, the patient began to recover; he was discharged on the 10th day. After 3 months of follow-up, only left arm rigidity and a left hand tremor persisted.

Acute- and convalescent-phase serum samples (taken 10 and 16 days after onset of illness, respectively) were sent to the Arbovirus and Arenavirus Disease Laboratory, Instituto de Virologia, Cordoba. SLEV immunoglobulin (Ig) M antibodies were positive by indirect immunofluorescence assay (IFA). Seroconversion for IgG antibodies was demonstrated by IFA (7) and hemagglutination inhibition assay, with titers of 640 and 80 in the first sample and 2,560 and 320 in the second sample. These results were confirmed by neutralization test using the reduction of plates technique in Vero cells culture, as described (8). Eastern equine encephalomyelitis virus and Western equine encephalomyelitis viruses with known circulation in Argentina were included in the assay with negative results (3). An increase in antibodies titers between acute- (320) and convalescent-phase (1,280) samples was found only for SLEV. Among other flaviviruses, dengue, yellow fever, and Ilheus circulate only in subtropical areas of Argentina (the province of Cordoba is not included in this area); only dengue virus was investigated (by neutralization test) because of a current epidemiologic surveillance program; results were negative. No evidence that West Nile virus is currently circulating or has entered Argentina was found, so we did not perform tests to detect it (2,9). Isolation of SLEV from the cerebrospinal fluid and blood was attempted in newborn mice and Vero cell cultures with negative results.

While the typical clinical manifestations of viral encephalitis (fever, headache, and altered level of consciousness) are indistinguishable from each other, tremor and other extrapyramidal signs are described in St. Louis encephalitis and Japanese encephalitis (10). The typical MRI finding of patients with St. Louis encephalitis is localized in the substantia nigra (11).

In summary, the occurrence of St. Louis encephalitis in a 61-year-old patient, after >10 years of no reports in Argentina, along with specific epidemiology, suggest that further studies are needed to assess the risk for human infection by SLEV in Argentina and the role of several mosquito species in its transmission.

Acknowledgments

We thank Gabriela Barbas, Daniela Valladares, and Femando Canna for their technical assistance.

This study was supported in part by Agencia Cordoba Ciencias and Secretaria de Ciencia y Tecnologia (SECYT) of the National University of Cordoba, Argentina.

Lorena Spinsanti, * Ana L. Basquiera, ([dagger]) Sebastian Bulacio, ([double dagger]) Veronica Somale, ([dagger]) Stefano C.H. Kim, ([dagger]) Viviana Re, * Damian Rabbat, ([double dagger]) Abel Zarate, ([dagger]) Juan C. Zlocowski, ([dagger]) Carlos Quiroga Mayor, ([double dagger]) Marta Contigiani, * and Santiago Palacio ([dagger])

* Universidad Nacional de Cbrdoba, Cordoba, Argentina; ([dagger]) Hospital Privado Centro Medico de Cordoba, Cordoba, Argentina; and ([double dagger]) Instituto de Radiologia Conci-Carpinella, Cordoba, Argentina

References

(1.) Calisher CH, Medically important arboviruses, of the United States and Canada. Clin Microbiol Rev 1994;7:89-116.

(2.) Sabattini MS, Aviles G, Monath TP. Historical, epidemiological and ecological aspects of arboviruses 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 neighboring countries. Belem, Brazil: Instituto Evandro Chagas; 1998. p. 113-34.

(3.) Sabattini MS, Monath TP, Mitchell CJ, Daffner GS, Bowen R, Pauli R, et al. Arbovirus investigations in Argentina, 1977-1980. I. Historical aspects and descriptions of study sites. Am J Trop Med Hyg 1985;34:937-44.

(4.) Spinsanti LI, Re V, 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.

(5.) Mettler NE, Casals J. Isolation of St. Louis encephalitis virus from man in Argentina. Acta Virol 1971;15:148-54.

(6.) Durlach RA, Astarloa L. Saint Louis meningoencephalitis. Medicina (B Aires) 1985;45:467-8.

(7.) Spinsanti L, Re V, Aguilar J, Contigiani M. An indirect immnunofluorescence assay to detect antibodies against St. Louis encephalitis virus. Rev Inst Med Trop Sao Paulo 2001;43:339-40.

(8.) Early E, Peralta PH, Johnson KM. A plaque neutralization method for arboviruses. Proc Soc Exp Biol Med 1967;25:741-7.

(9.) Aviles G, Rangeon G, Vorndam V, Briones A, Baroni P, Enria D, et al. Dengue reemergence in Argentina. Emerg Infect Dis 1999;5:575-8.

(10.) Southern PM, Smith JW, Luby JP, Barnett JA, Sanford JP. Clinical and laboratory features of epidemic St. Louis encephalitis. Ann Intern Med 1969;71:681-9.

(11.) Cerna F, Mehrad B, Luby JP, Burns D, Fleckenstein JL. St. Louis encephalitis and the substantia nigra: MR imaging evaluation. Am J Neuroradiol 1999;20:1281-3.

Address for correspondence: Ana Lisa Basquiera, Department of Internal Medicine, Hospital Privado Centro Medico de Cordoba, Naciones Unidas 346, (5016) Cordoba, Argentina; fax: [phone]; e-mail: [e-mail]