Relapsed and late-onset Nipah encephalitis, a report of three cases

The Nipah virus that caused a fatal outbreak among Malaysian pig-farmers in 1998-1999 was known to cause relapsed and late-onset encephalitis. We report 2 patients with relapsed and one patient with late-onset encephalitis up to 53 months after the initial infection. Two of the patients were husband and wife and they developed relapsed and late-onset encephalitis within 5 days of each other. This report suggests that Nipah virus could cause relapsed and late-onset encephalitis after lying dormant for more than 4 years. Environmental factor could be important in precipitating the relapsed and late-onset encephalitis, perhaps by transiently suppressing the immune system. Neurol J Southeast Asia 2003; 8 : 109 – 112 Address correspondence to: Dr HT Chong, Neurology Laboratory, University Malaya Medical Centre, 59100 Kuala Lumpur, Malaysia. Fax: 603-79502968 INTRODUCTION Nipah virus caused severe acute encephalitis with high mortality among pig farmers during an outbreak in Malaysia in 1998 – 1999.1-7 Nipah virus infection present clinically mainly as acute encephalitis, with short incubation period of less than two weeks, with fever, headache, giddiness followed by coma. Distinctive clinical signs include segmental myoclonus, areflexia and hypotonia, hypertension and tachycardia. The mortality was 32 – 41%. Some 40 – 53% of patients recovered fully, with 15 – 19% having persistent neurological deficits.3,4 Nipah virus infects the endothelial cells, leading to syncytial formation and necrosis of these cells, thus causing a systemic vasculitis with extensive thrombosis, resulting in parenchymal necrosis, the most important site being the central nervous system.6 The virus also affects the neurons directly, explaining the distinctive neurological features.3 Subsequently it was reported that 12 out of the 160 (7.5%) survivors and 10 of the 89 (3.4%) non-encephalitic or asymptomatic patients developed a relapsed and late-onset Nipah encephalitis up to 24 months after the initial outbreak. These patients presented with fever, headache, seizure and focal neurological deficits, with a mortality of 18%. MR imaging showed patchy areas of confluent cortical lesions. In between the acute infection and the relapses the patients were well. Necropsy of 2 cases showed changes of focal encephalitis with positive immunolocalization for Nipah virus antigen, but without vasculitis, the hallmark of acute Nipah infection and perivenous demyelination. It was believed that the relapsed and late-onset encephalitis represented rapid viral replication in the brain parenchyma, after a quiescent period.8 This is a report of 2 other patients with acute Nipah encephalitis and one patient with nonencephalitic Nipah virus infection during the initial outbreak, who later developed relapsed and late-onset Nipah encephalitis, up to 4 + years after the outbreak.