New initiatives for the control of Japanese encephalitis by vaccination: minutes of a WHO/CVI meeting, Bangkok, Thailand, 13-15 October 1998.

Japanese encephalitis vaccines

Japanese encephalitis (JE) virus is a mosquito-borne zoonotic flavivirus that infects a wide range of vertebrate species in an enzootic cycle primarily of large waterfowl birds and swine. Horses and humans are considered bystanders to this enzootic cycle and, once infected, dead-end hosts. JE infection in humans can manifest in a spectrum of disease from asymptomatic infection to a mildly febrile symptomatic illness to a life-threatening disease affecting the central nervous system (CNS). The latter is associated with a high morbidity and mortality as well as long-term neurologic sequelae. The pathogenesis and disease severity of JE is discussed elsewhere in this volume. JE is the most common cause of encephalitis in most of Asia and causes an estimated 35,000 cases of encephalitis annually (Igarashi 1992). By all accounts this is an underestimate of the true disease burden of this virus and evidence suggests that this virus is endemic over a far wider region today than 50 years ago, despite the use of an effective vaccine for humans and animals.

Japanese encephalitis virus: ecology and epidemiology.

Japanese encephalitis (JE) virus is the most important cause of epidemic encephalitis worldwide with an estimated 30,000–50,000 cases annually (Solomon 2000). The geographical area affected by the virus is expanding, and despite the availability of vaccines, JE is a growing public health problem (Tsai 2000; Vaughn and Hoke 1992). The closely related West Nile (WN) virus is the most widely distributed member of the JE virus complex of flaviviruses. Until recently it was considered to be a relatively benign virus, causing epidemics of a fever—arthralgia—rash syndrome, and only occasional central nervous system (CNS) disease (Solomon and Cardosa 2000). However, its importance has grown with recent outbreaks of West Nile encephalitis (WNE) in Romania and New York (Anonymous 1999; Tsai et al. 1998). For both JE and WN viruses the number of people who present with clinical features represents only a small proportion of those infected. In addition, both diseases have a broad spectrum of clinical manifestations, ranging from a nonspecific febrile illness to a severe meningoencephalomyelitis (inflammation of the meninges, brain matter, and spinal cord). In this chapter, we will look at factors that determine who, of all those infected with JE or WN virus, develops disease. Secondly we will describe the clinical features of infection with JE and WN viruses and consider the extent to which pathophysiological and pathological studies explain these features. Finally we will consider the diagnosis and management of JE and WNE and the prospects for future therapies.

Pathogenesis and Clinical Features of Japanese Encephalitis and West Nile Virus Infections

The distribution of virus and the composition of the mononuclear inflammatory response were studied in the brains of 7 children who died with Japanese encephalitis. Viral antigen was localized to neurons, with greatest involvement in the thalamus and brainstem. Quantitation of perivascular inflammatory responses showed a preponderance of T cells, but only 7 to 30% of these cells were T suppressor/cytotoxic cells. Inflammatory cells invading the parenchyma were predominantly macrophages with small numbers of T cells. B cells remained localized to perivascular cuffs. Viral antigen was progressively cleared in patients with survival of 6 days or more.

Japanese encephalitis: immunocytochemical studies of viral antigen and inflammatory cells in fatal cases.

In order to determine if prior dengue virus infection reduces the severity of Japanese encephalitis (JE), we examined 127 patients hospitalized during the 1970 JE epidemic in the Chiangmai and Lampang Valleys of northern Thailand. Patients were studied during the first 30 days after onset of JE; 120 of these patients were examined one year later for residual neurologic sequelae. About 21% of patients had serological evidence of a prior dengue virus infection. Morbidity and mortality in patients with and without prior dengue virus experience were compared. These comparisons were made within two age groups to exclude differences due to age alone;

P Voodhikul

Papers

The effect of dengue virus infection on the clinical sequelae of Japanese encephalitis: a one year follow-up study in Thailand.