Box 1: Diagnostic Tests for Japanese Encephalitis

Figure 1 : Global distribution pattern of Japanese encephalitis. The areas shaded in yellow are Japanese encephalitis

risk-prone regions. The areas encircled in red, such as Karachi (Pakistan) and Torres Strait islands (Australia) and

parts of the northern Australian mainland are newer areas affected by Japanese encephalitis.

Figure 2: Japanese Encephalitis Virus Life-Cycle

Figure 3: A schematic representation of the Japanese encephalitis virus genome. The genome is a single-stranded,

plus-sense RNA molecule containing a long open reading frame (ORF) encoding the viral polyprotein with 5’ and 3’

Figure 4 : Opisthotonus in a boy with JE (Photo: Courtesy Dr. P. Nagabhushana Rao)

Figure 5: Dystonia in the right hand of a boy with JE (Photo: Courtesy Dr. P. Nagabhushana Rao)

Figure 6: Left hemiparesis in a child with JE (Photo: Courtesy Dr. P. Nagabhushana Rao)

Figure 7: Right gaze palsy in a child with JE (Photo: Courtesy Dr. P. Nagabhushana Rao)

Figure 8 : (A) CT scan showing thalamic hypodensity; (B) MRI scan showing hyperintense thalami

(Photos: Courtesy Dr. P. Nagabhushana Rao)

(A) (B)

Figure 9 : (A) MRI T2WI of a JE patient showing bilateral thalamic hyperintensity; (B) SPECT showing thalamic and left frontal

hypoperfusion in a child with JE who had mouth open dystonia (Photos: Courtesy Dr. U.K. Misra)

(A) (B)

Figure Figure 10 : Bed sore on the head of a JE patient (Photo: Courtesy Dr. P. Nagabhushana Rao)

Table 1 : Japanese Encephalitis : An Historical Timeline

Year	Incident
1871	First recorded clinical case of JE, reported from Japan
1924	Large outbreak of JE in Japan with >6,000 cases and a fatality rate of 60%; Isolation of JEV from human brain
1933	First cases of JE reported from the Korean peninsula
1935	Isolation of Nakayama strain of JEV
1938	Isolation of JEV from Culex tritaeniorhynchus mosquitoes
1940	First cases of JE reported from the Chinese Mainland
1950	First cases of JE reported from the Philippines
1950s	Elucidation of transmission cycle of JEV, with pigs and ardeid birds identified as amplifying hosts and Culex tritaeniorhynchus as primary vector species
1955	First cases of JE reported from Vellore, India
1965	Major epidemic in northern Vietnam
1969 and 1970	Major epidemic in Chiang Mai Valley, Thailand
1973	First epidemic in India, in the state of West Bengal
1978	Major epidemic in Terai region of Nepal
1983	JE reaches Pakistan, the furthest geographical extension to the West
1985-86 and 1987	Major epidemics in Sri Lanka
1995	JE reaches Papua New Guinea and Torres Strait islands (Australia), the furthest geographical extension to the South
2005	Major epidemic in Gorakhpur, Uttar Pradesh state of India. 5,737 cases, with 1,344 deaths; India imports live-attenuated SA 14-14-2 vaccine from China

Table 2 : Major Human Flaviviruses and their Endemic Areas

VIRUS	ENDEMIC AREAS
Japanese encephalitis	Asia and Oceania
Yellow fever	South American and Africa
Dengue	Tropics, worldwide
West Nile	Europe, Africa, Asia and North America
St. Louis encephalitis	North and South America
Murray Valley encephalitis	Australia
Tick-borne encephalitis	Europe and Asia

Table 3 : Japanese Encephalitis – Facts & Figures

Causative agent	Japanese encephalitis virus (JEV) : Single-stranded, positive-sense, RNA virus. Family: Flaviviridae. Genus: Flavivirus.
Geographic range	Indian subcontinent (including Pakistan), South Asia, Southeast Asia, China, Oceania, Northern Australia
Major vectors	Paddy-breeding mosquitoes of the Culex vishnui subgroup, particularly Cx. tritaeniorhynchus. Other important secondary or regional vectors include Cx. gelidus, Cx. fuscocephala, Cx. pipiens, Cx. annulirostris
Major vertebrate hosts	Domestic pigs (amplifying hosts); ardeid wading birds such as the black-crowned night heron (Nycticorax nycticorax), plumed egret (Egretta intermedia), and little egret (Egretta garzetta) (primary enzootic hosts); domestic fowls; migratory birds
High risk groups	Infants and children below 10 years in endemic areas; the elderly in endemic areas; non-immune adults (e.g. travelers from non-endemic countries visiting JE endemic areas for more than a month); immunocompromised individuals
Annual estimated cases	~175,000
Annual reported cases	~ 50,000
Annual reported morbidity	~ 15,000
Annual reported mortality	~ 10,000

Table 4 : JE-Related Statistics from Major JE-Endemic Countries

Table 5 : Vaccines Against Japanese encephalitis

Vaccine name	Type	Virus strain	Manufacturer	Dosing	Status
JE-VAX^®	Mouse brain-derived; Inactivated	Nakayama	BIKEN, Japan; Green Cross, South Korea; Central Research Institute (CRI), India	Three doses at 0, 7, 30 days. Boosting after 1 year and subsequently every 3 years till child is 10 years of age.	JE vaccine production stopped by BIKEN (Japan) and CRI (India); current stocks of Green Cross likely to be exhausted soon
SA 14-14-2	PHK cell-cultured; Live-attenuated	SA 14-14-2	Chengdu Institute of Biological Products, China	Single dose	Currently in use in China, India, Korea, Sri Lanka and Nepal; WHO prequalification likely in 2009
IXIARO^®	Vero cell-cultured; purified- inactivated	SA 14-14-2	Intercell, Austria	Two doses at 0 and 30 days	USFDA approved. Launch in USA in late 2009
Chimeri-Vax-JE^(TM)	Infectious clone; Live-attenuated	JEV SA 14-14-2 and YF 17D chimeric infectious clone	Acambis, UK; Sanofi Pasteur	Single dose	Phase III trials in USA, Australia and Asia