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 ∂“∫—π«‘®—¬«‘∑¬“»“ µ√å°“√·æ∑¬å∑À“√                                                        121
   Armed Forces Research Institute of Medical Sciences



MOPH instituted a JE vaccination program providing two doses of killed JE vaccine (18 and 24
months) and a booster (2.5-3 years) without a “catch-up” component. Between 1990-91, routine
childhood JE vaccination began in all northern provinces. Characterization of encephalitis in
southern Thailand, and subsequent institution of routine JE vaccination was delayed. The authors
hypothesized there was endemic JE in Southern Thailand.
Methods: From 1989-90, all febrile children hospitalized with CNS signs and symptoms unrelated
to a bacterial infection were evaluated at Surat Thani Hospital, a regional medical center in
Southern Thailand. Hospital course and outcome were recorded; serum and CSF specimens
were obtained for JE, dengue, and rickettsial serology.
Results: 119 patients had complete evaluations: 53 in 1989 and 66 in 1990. Of 119 cases, 94
(79%) were diagnosed as encephalitis and JE was the etiology in 53 (45%). JE accounted for 52%
of encephalitis cases and the frequency of sequelae or death was 50%. By 1994, JE vaccination
was occurring in 36 provinces and by 1999 there was a coverage rate of 84% for children between
2.5-3 years of age. Surat Thani encephalitis data published by the MOPH reports that from
1981-88 there were 254 encephalitis and 2 JE cases. During the 1989-90 study period, the MOPH
reported 85 encephalitis cases and no JE. The author’s investigation revealed 94 encephalitis
cases, 53 due to JE. During the 7 year period (1995-2001) following the introduction of routine
JE vaccination, the MOPH reported 94 encephalitis cases, 8 as JE.
Conclusions: 1) JE was the main cause of pediatric non-bacterial CNS infections in the Surat
Thani region between 1989-90; 2) JE caused significant morbidity and mortality; and 3) in
contrast to the authors' data, MOPH data for the Surat Thani region fails to indicate a benefit
to routine JE vaccination. Additional research is required to: a) confirm JE transmission patterns,
b) confirm vaccination rates, c) confirm the availability of JE diagnostics, and d) discover
reporting deficiencies.

Abstract of the International Conference on Emerging Infectious Diseases. Atlanta,
Georgia, U.S.A. 29 February – 3 March 2004. Poster Board 35:127.


JAPANESE ENCEPHALITIS VIRUS: ECOLOGY AND EPIDEMIOLOGY
Nisalak A

Japanese Encephalitis (JE), a mosquito-borne arboviral infection, is recognized throughout
much of Asia and is considered the most important mosquito-born viral encephalitis, with an
estimated worldwide incidence of 45,000 cases each year primarily in children. Approximately
25 percent of cases die and 50 percent develop permanent neurologic and psychiatric sequelae.
The magnitude of the problem is even more impressive when it is considered that the disease
often occurs in epidemics that are somewhat predictable and that Japanese encephalitis is a
vaccine preventable disease. Cycle of Japanese encephalitis in nature is dicussed. Pig and ardeid
birds are the most important hosts for maintenance, amplification, and spread of the virus. The
primary vector species are Culex mosquitoes. Study on Ecology in Japan in 1964, and in Bangkok
by AFRIMS 1985 is also discussed. Countries officially reporting Japanese Encephalitis to WHO
are presented. Countries reporting cases include JE countries at-risk, reporting cases of JE, not
reporting cases of JE, and inconsistent reporting cases. Distribution of JE cases by age-group



                                   √“¬ß“πª√–®”ªï 2547        Annual Report 2004
122                                                                         ∂“∫—π«‘®—¬«‘∑¬“»“ µ√å°“√·æ∑¬å∑À“√
                                                              Armed Forces Research Institute of Medical Sciences



is discussed. Problems of epidemiologic data are : most national disease reporting systems
report the total numbers of encephalitis cases, the lack of diagnostic precision has increased
difficulty of undertaking focused disease control programs for Japanese encephalitis, as long
as all ecologic components required for transmission remain in the environment and the risk
of acquiring the disease will continue, vaccine should be made widely at low cost to prevent
disease.

Workshop on JE surveillance IVI (International Vaccine Institute). Bali, Indonesia. 31
July-3 August 2004.


EVALUATION OF AN IMMUNOCHROMATOGRAPHIC ASSAY FOR
THE RAPID DIAGNOSIS OF ACUTE HEPATITIS E INFECTION
Myint KS, Ming G, Ying H, Yang L, Anderson D, Howard T and Mammen MP Jr

There is an urgent need for a rapid and reliable diagnostic assay for acute hepatitis E virus (HEV)
infection in endemic areas, particularly for outbreak situations. At present, there is no gold
standard for the diagnosis of acute HEV infection. Most cases are diagnosed using an anti-HEV
IgM ELISA or RT-PCR. A rapid, immunochromatographic assay for anti-HEV IgM (Genelabs
Diagnostics) was evaluated on acute HEV serum samples characterized by positive HEV RT-PCR
and anti-HEV IgM > 100 WRAIR Units (n = 200) obtained from patients with clinical hepatitis
in Indonesia and Nepal, healthy blood donors in Thailand (n = 100) and acute hepatitis A (n = 80),
acute hepatitis B (n = 45) and acute hepatitis C (n = 50) in Thailand, Nepal, Cambodia and
Indonesia. The assay performed with 93% sensitivity and 100% specificity for the diagnosis
of HEV infection in acute hepatitis samples with no false positives when performing the assay
on the acute hepatitis A, B C samples and on samples from healthy blood donors. This data
suggests that this assay may be a valuable tool for the rapid diagnosis of acute HEV infection.
Additional evaluation in HEV endemic regions with varying antigen concentrations may improve
the testing sensitivity without compromising specificity.

53rd Annual Meeting of the American Society Tropical Medicine and Hygiene (ASTMH).
Miami, Florida, USA. 7-11 November 2004.

Am J Trop Med Hyg. 2004; 70(4 suppl):163.


A BLUNTED BLOOD PLASMACYTOID DENDRITIC CELLS
RESPONSE IN AN ACUTE SYSTEMIC VIRAL INFECTION IS
ASSOCIATED WITH INCREASED DISEASE SEVERITY
Pichyangkul S, Endy TP, Kalayanarooj S, Nisalak A, Youngvanitchit K, Mahanonda R,
Green S, Rothman AL, Ennis FA and Libraty DH

At least two distinct human dendritic cell (DC) subsets are produced in the bone marrow and
circulate in the peripheral blood-precursor myeloid DCs (pre-mDCs) and plasmacytoid DCs
(PDCs). Both lineages of DCs are instrumental in antiviral innate immunity and shaping Th1



                        √“¬ß“πª√–®”ªï 2547                   Annual Report 2004

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japanese encephalitis

  • 1.  ∂“∫—π«‘®—¬«‘∑¬“»“ µ√å°“√·æ∑¬å∑À“√ 121 Armed Forces Research Institute of Medical Sciences MOPH instituted a JE vaccination program providing two doses of killed JE vaccine (18 and 24 months) and a booster (2.5-3 years) without a “catch-up” component. Between 1990-91, routine childhood JE vaccination began in all northern provinces. Characterization of encephalitis in southern Thailand, and subsequent institution of routine JE vaccination was delayed. The authors hypothesized there was endemic JE in Southern Thailand. Methods: From 1989-90, all febrile children hospitalized with CNS signs and symptoms unrelated to a bacterial infection were evaluated at Surat Thani Hospital, a regional medical center in Southern Thailand. Hospital course and outcome were recorded; serum and CSF specimens were obtained for JE, dengue, and rickettsial serology. Results: 119 patients had complete evaluations: 53 in 1989 and 66 in 1990. Of 119 cases, 94 (79%) were diagnosed as encephalitis and JE was the etiology in 53 (45%). JE accounted for 52% of encephalitis cases and the frequency of sequelae or death was 50%. By 1994, JE vaccination was occurring in 36 provinces and by 1999 there was a coverage rate of 84% for children between 2.5-3 years of age. Surat Thani encephalitis data published by the MOPH reports that from 1981-88 there were 254 encephalitis and 2 JE cases. During the 1989-90 study period, the MOPH reported 85 encephalitis cases and no JE. The author’s investigation revealed 94 encephalitis cases, 53 due to JE. During the 7 year period (1995-2001) following the introduction of routine JE vaccination, the MOPH reported 94 encephalitis cases, 8 as JE. Conclusions: 1) JE was the main cause of pediatric non-bacterial CNS infections in the Surat Thani region between 1989-90; 2) JE caused significant morbidity and mortality; and 3) in contrast to the authors' data, MOPH data for the Surat Thani region fails to indicate a benefit to routine JE vaccination. Additional research is required to: a) confirm JE transmission patterns, b) confirm vaccination rates, c) confirm the availability of JE diagnostics, and d) discover reporting deficiencies. Abstract of the International Conference on Emerging Infectious Diseases. Atlanta, Georgia, U.S.A. 29 February – 3 March 2004. Poster Board 35:127. JAPANESE ENCEPHALITIS VIRUS: ECOLOGY AND EPIDEMIOLOGY Nisalak A Japanese Encephalitis (JE), a mosquito-borne arboviral infection, is recognized throughout much of Asia and is considered the most important mosquito-born viral encephalitis, with an estimated worldwide incidence of 45,000 cases each year primarily in children. Approximately 25 percent of cases die and 50 percent develop permanent neurologic and psychiatric sequelae. The magnitude of the problem is even more impressive when it is considered that the disease often occurs in epidemics that are somewhat predictable and that Japanese encephalitis is a vaccine preventable disease. Cycle of Japanese encephalitis in nature is dicussed. Pig and ardeid birds are the most important hosts for maintenance, amplification, and spread of the virus. The primary vector species are Culex mosquitoes. Study on Ecology in Japan in 1964, and in Bangkok by AFRIMS 1985 is also discussed. Countries officially reporting Japanese Encephalitis to WHO are presented. Countries reporting cases include JE countries at-risk, reporting cases of JE, not reporting cases of JE, and inconsistent reporting cases. Distribution of JE cases by age-group √“¬ß“πª√–®”ªï 2547 Annual Report 2004
  • 2. 122  ∂“∫—π«‘®—¬«‘∑¬“»“ µ√å°“√·æ∑¬å∑À“√ Armed Forces Research Institute of Medical Sciences is discussed. Problems of epidemiologic data are : most national disease reporting systems report the total numbers of encephalitis cases, the lack of diagnostic precision has increased difficulty of undertaking focused disease control programs for Japanese encephalitis, as long as all ecologic components required for transmission remain in the environment and the risk of acquiring the disease will continue, vaccine should be made widely at low cost to prevent disease. Workshop on JE surveillance IVI (International Vaccine Institute). Bali, Indonesia. 31 July-3 August 2004. EVALUATION OF AN IMMUNOCHROMATOGRAPHIC ASSAY FOR THE RAPID DIAGNOSIS OF ACUTE HEPATITIS E INFECTION Myint KS, Ming G, Ying H, Yang L, Anderson D, Howard T and Mammen MP Jr There is an urgent need for a rapid and reliable diagnostic assay for acute hepatitis E virus (HEV) infection in endemic areas, particularly for outbreak situations. At present, there is no gold standard for the diagnosis of acute HEV infection. Most cases are diagnosed using an anti-HEV IgM ELISA or RT-PCR. A rapid, immunochromatographic assay for anti-HEV IgM (Genelabs Diagnostics) was evaluated on acute HEV serum samples characterized by positive HEV RT-PCR and anti-HEV IgM > 100 WRAIR Units (n = 200) obtained from patients with clinical hepatitis in Indonesia and Nepal, healthy blood donors in Thailand (n = 100) and acute hepatitis A (n = 80), acute hepatitis B (n = 45) and acute hepatitis C (n = 50) in Thailand, Nepal, Cambodia and Indonesia. The assay performed with 93% sensitivity and 100% specificity for the diagnosis of HEV infection in acute hepatitis samples with no false positives when performing the assay on the acute hepatitis A, B C samples and on samples from healthy blood donors. This data suggests that this assay may be a valuable tool for the rapid diagnosis of acute HEV infection. Additional evaluation in HEV endemic regions with varying antigen concentrations may improve the testing sensitivity without compromising specificity. 53rd Annual Meeting of the American Society Tropical Medicine and Hygiene (ASTMH). Miami, Florida, USA. 7-11 November 2004. Am J Trop Med Hyg. 2004; 70(4 suppl):163. A BLUNTED BLOOD PLASMACYTOID DENDRITIC CELLS RESPONSE IN AN ACUTE SYSTEMIC VIRAL INFECTION IS ASSOCIATED WITH INCREASED DISEASE SEVERITY Pichyangkul S, Endy TP, Kalayanarooj S, Nisalak A, Youngvanitchit K, Mahanonda R, Green S, Rothman AL, Ennis FA and Libraty DH At least two distinct human dendritic cell (DC) subsets are produced in the bone marrow and circulate in the peripheral blood-precursor myeloid DCs (pre-mDCs) and plasmacytoid DCs (PDCs). Both lineages of DCs are instrumental in antiviral innate immunity and shaping Th1 √“¬ß“πª√–®”ªï 2547 Annual Report 2004