Elsevier

The Lancet

Volume 354, Issue 9186, 9 October 1999, Pages 1257-1259
The Lancet

Articles
Fatal encephalitis due to Nipah virus among pig-farmers in Malaysia

https://doi.org/10.1016/S0140-6736(99)04299-3Get rights and content

Summary

Background

Between February and April, 1999, an outbreak of viral encephalitis occurred among pig-farmers in Malaysia. We report findings for the first three patients who died.

Methods

Samples of tissue were taken at necropsy. Blood and cerebrospinal-fluid (CSF) samples taken before death were cultured for viruses, and tested for antibodies to viruses.

Findings

The three pig-farmers presented with fever, headache, and altered level of consciousness. Myoclonus was present in two patients. There were signs ofbrainstem dysfunction with hypertension and tachycardia. Rapid deterioration led to irreversible hypotension and death. A virus causing syncytial formation of vero cells was cultured from the CSFof two patients after 5 days; the virus stained positively with antibodies against Hendra virus by indirect immunofluorescence. IgM capture ELISA showed that all three patients had IgM antibodies in CSF against Hendra viral antigens. Necropsy showed widespread microinfarction in the central nervous system and other organs resulting from vasculitis-induced thrombosis. There was no clinical evidence of pulmonary involvement. Inclusion bodies likely to be of viral origin were noted in neurons near vasculitic bloodvessels.

Interpretation

The causative agent was a previously undescribed paramyxovirus related to the Hendra virus. Close contact with infected pigs may be the source of the viral transmission. Clinically and epidemiologically the infection is distinct from infection by the Hendra virus. We propose that this Hendra-like virus was the cause of the outbreak of encephalitis in Malaysia.

Introduction

Between February and April, 1999, there was a severe outbreak of viral encephalitis among pig-farmers in the Bukit Pelandok area in Negri Sembilan state, Malaysia, that affected more than 200 individuals. 91 patients from the outbreak area were admitted to the University of Malaya Medical Centre, Kuala Lumpur, and there were 28 deaths. Because this outbreak occurred among people in close contact with pigs, the differential diagnoses included Japanese encephalitis. Features that distinguished this outbreak from Japanese encephalitis included: infection predominantly in adults rather than children; clustering of cases in members of the same household, which suggests an infection with high disease attack rate (as opposed to the Japanese-encephalitis virus which causes symptomatic encephalitis in one in 300 of those infected); a high proportion of patients in direct contact with pigs as opposed to other individuals living in the same neighbourhood (evidence against a mosquito-borne disease); a history of illness in the pigs belonging to affected farmers; and the fact that many patients have had previous immunisation against Japanese encephalitis.1

We report on the first three fatal cases seen at our hospital. All three patients were farmers with a history of direct contact with pigs.

Section snippets

Patient 1

This 51-year-old man was admitted to hospital with fever (2 days since onset), acute confusion (1 day), and pain associated with myoclonus in the left arm. He had received two doses of Japanese-encephalitis vaccine, the second dose more than a month before onset of illness. On admission, his temperature was 38°C and he was disoriented. The patient's pupils were reactive, and doll's eye reflex was present. There was no focal limb weakness and no meningism. Examination of the heart and lungs

Histopathology

Samples from all three patients showed similar histological findings of endothelial damage and vasculitis (mainly in arterioles, capillaries, and venules, although these features were also seen in some large muscular arteries). The brain was the most severely affected organ, but other organs including the lung, heart, and kidney were also affected. Vasculitic vessels were characterised by vessel-wall necrosis, thrombosis, and inflammatory-cell infiltration of neutrophils and mononuclear cells (

Discussion

The virus implicated in this outbreak is related to but distinct from the Hendra virus. Clinically and epidemiologically the disease in our three patients differed from the previously described Hendra-virus infection.4, 5, 6 Hendra virus was transmitted from horses, and two of the three reported patients with Hendra infection had respiratory involvement, with only one patient showing a severe meningoencephalitis. In our patients, however, the infection involved direct contact with pigs and

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