Treatment of West Nile Virus Encephalitis with Intravenous Immunoglobulin.

To the Editor: West Nile virus is endemic in Israel. The overwhelming majority of infections are mild and asymptomatic, but there have been periodic symptomatic outbreaks (1). In August 2000, an epidemic of West Nile virus broke out in Israel, with [is greater than] 260 confirmed cases and 20 deaths by the end of September 2000. Hitherto, the only treatment for [his condition has been supportive with no proven in vivo specific therapy, although ribavirin has shown promise in in vitro studies (2). We report an apparent dramatic response to intravenous immunoglobulin in an immunosuppressed patient and suggest that this was the result of specific antibodies in the Israeli immunoglobulin used.

A 70-year-old woman was admitted to the hospital because of fever and vomiting of 24 hours' duration. She had a 12-year history of chronic lymphatic leukemia (Rai stage II) but was not on treatment. A routine outpatient assessment 1 week earlier had shown no unexpected findings.

On physical examination the patient appeared generally well, with temperature 39.0 [degrees] C, regular pulse 100/ minute, and blood pressure 130/70. Apart from splenomegaly 2-3 cm below the costal margin, there were no abnormal physical signs, including lymphadenopathy. Chest X ray results were normal. Hb was 12 g/dL, HCt 32%, mean corpuscular volume 84, leukocyte count 280x[10.sup.9]/L (90% lymphocytes, 13% neutrophils, and 10% monocytes), platelets 280x[10.sup.9]/L, Coombs negative. Her biochemical profile was entirely within the normal range. Blood and urine cultures were negative. Immunoglobulin G (IgG) was 14.5 g/L, IgM 2.6 g/L, and IgA 2.6 g/L.

Forty-eight hours after admission, dysarthria with episodes of impaired consciousness developed. After a further 24 hours, she was in deep coma (Glasgow Coma Scale, 6). Empiric treatment for presumed central nervous system infection was begun with ceftriaxone, ampicillin, acyclovir, and amphotericin B. Results of cranial computerized tomography were normal. A lumbar puncture was performed and showed clear cerebrospinal fluid (CSF) at normal pressure. CSF protein was 1.04 g/L, glucose 2.4 mmol/L, and leukocyte count 162/[mm.sup.3] (90% mononuclear cells). Gram stain was negative, as were bacterial culture, cryptococcal antigen, and results of a polymerase chain reaction test for herpes viruses. IgM antibodies against West Nile virus were positive in both serum and CSF.

With the definite diagnosis of West Nile encephalitis, all antimicrobial treatment was stopped. Because of the chronic lymphatic leukemia and presumed immunosuppression, we decided to give intravenous immunoglobulin (Omr-IgG-am, Omrix Biopharmaceutical Ltd, Tel Hashomer, Israel), 0.4 g/kg, as has been recommended for this condition (3). The patient's neurologic condition remained unchanged (Glasgow coma scale, 5-6) for the next 2 days but then began to improve. Over the subsequent 5 days, her level of consciousness returned to normal.

In light of this apparently dramatic response to treatment with intravenous immunloglobulin, we examined several batches of pooled immunoglobulin from different sources for antibodies to West Nile virus. Intravenous immunoglobulin preparations from donors in Israel, such as our patient received, contained high titers (1:1,600) of such antibodies, while those from the USA had no detectable antibody. We suggest that the use of such antibody-containing immunoglobulin may provide a specific and effective treatment for serious cases of West Nile virus infections, and therefore that formal trials of its use should be carried out.

Acknowledgment

We thank Ella Mendelson, Director of the Central Virology Laboratory, Ministry of Health of Israel, for the measurements of West Nile virus antibody.

References

(1.) Cohen D, Zaide Y, Karasenty E, Schwarz M, LeDuc JM, Slepon R, et al. Prevalence of antibodies to West Nile fever, sandfly fever Sicilian, and sandfly fever Naples viruses in healthy adults in Israel. Public Health Rev 1999;27:217-30.

(2.) Jordan I, Briese T, Fischer N, Lau JY, Lipkin WI. Ribavirin inhibits West Nile virus replication and cytopathic effect in neural cells. J Infect Dis 2000;182:1214-17.

(3.) Cooperative Group for the Study of Immunoglobulin in Chronic Lymphocytic Leukemia. Intravenous immunoglobulin for the prevention of infection in chronic lymphocytic leukemia: a randomized, controlled clinical trial. N Engl J Med 1988;1319:902-7.

Zvi Shimoni,(*) Mark J. Niven,(*) Silvio Pitlick,([dagger]) and Shlomo Bulvik(*)

(*) Laniado Hospital, Kiryat Sanz, Netanya, Israel, and ([dagger]) Beilinson Hospital, Petach Tikva, Israel