The Features of Imported Dengue Fever Cases Confirmed at National Institute of Infectious Diseases Japan, during 2001+ by
Ken-Ichiro Yamada*#, Tomohiko Takasaki*, Masaru Nawa**, Reiko Nerome*, Yohko T Arai*, Kinjiro Morimoto* and Ichiro Kurane* *Department of Virology 1, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640 Japan **Department of Microbiology, Saitama Medical School, Japan Abstract The demographic features of the dengue cases confirmed during 2001 at the National Institute of Infectious Diseases, Japan, were determined. Thirty-five cases were confirmed to be of dengue fever, 18 cases were male and 17 female. The youngest case was 19 years old and the oldest was 64 years old. Thirty-four cases were determined to be of primary infection, and one was secondary. Most of the dengue patients developed illness after returning from countries in Southeast and South Asia. In addition, two patients had visited Tahiti and one had visited Samoa before developing dengue fever. Dengue fever/dengue haemorrhagic fever is the infectious disease that should attract more attention in Japan. Keywords: Dengue fever, imported cases, serodiagnosis, Japan.
Introduction Dengue fever/dengue haemorrhagic fever is one of the infectious diseases that all
physicians are required to report in Japan, according to the Japanese infectious disease control law. Dengue outbreaks occurred in
+ Information generated on the circulation of dengue serotypes is equally important for ‘travellers contact’ countries. Introduction of new DEN serotype has been found to be a good predictive indicator for larger epidemics. During the present study, out of the 21 virus genome detections from countries of South-East and South Asia, 15 isolations belonged to DEN-1 and three each to DEN-2 and DEN-3. DEN-1 was the predominant virus circulating in the region during 2001. Besides, this information is important for DHF/DSS case management. In Thailand it has been established that the severity of DEN-1 and DEN-2 is associated with more plasma leakage, more shock and complication with fluid overload cases, whereas DEN-3 and DEN-4 severity is associated with hepatic dysfunction and encephalophathy. Advance stocking of DEN serotype-specific requirements in hospitals will result in better case management and help in lowering the case fatality rates. – Editor
# For correspondence: kyamada@nih.go.jp
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Osaka, Kobe, Hiroshima and Nagasaki from 1942 to 1945(1). Dengue virus infection has not been epidemic in Japan since then, and there are no domestic dengue virus infections today. However, there have been dengue cases imported into Japan(2,3,4). Laboratory diagnosis is essential for the confirmation of dengue virus infection. We have performed laboratory diagnosis of dengue virus infection upon request from hospitals and clinics. The features of imported dengue cases that were confirmed at the National Institute of Infectious Diseases from 1985 to 2000 have been previously reported(2,3,4,5).
Brisbane, Australia) were purchased and used for serodiagnosis. RT-PCR was performed as previously reported(6,7). The primer sequences used to amplify each serotype of dengue viruses and target size were previously reported(6,7). HI test was done on microtiter plate, using 4 haemagglutinatin units of DEN-2 viral antigen as previously reported(2).
Results The summary of dengue cases confirmed at our laboratory during 2001 is given in the Table. Blood samples from 76 suspected cases were tested and 35 were confirmed to be of dengue. All the cases were of dengue fever, and there was no case of dengue haemorrhagic fever. Of the 35 confirmed dengue fever cases, 18 were male and 17 female. The youngest case was 19 years old and the oldest 64 years old. Most of the Japanese dengue patients developed illness after they had visited countries in Southeast and South Asia (Table), e.g. Indonesia (2), Thailand (8); Philippines (7); Cambodia (3), India (2), Tahiti (2), Viet Nam (1) and Samoa (1). There were nine patients who had visited more than one country. Thirty-four of the 35 cases were determined to be primary dengue virus infection based on antibody response. There was one patient (patient #27) who was determined to be of secondary dengue virus infection. This was the first secondary dengue case we experienced during the past five years.
Materials and methods Serum specimens were collected from dengue-suspected cases in clinics and hospitals, and sent to the Department of Virology 1, National Institute of Infectious Diseases, Tokyo, for laboratory diagnosis. In the present paper, we report the features of the dengue cases confirmed at our laboratory during 2001. Dengue virus infections were confirmed by IgM-capture enzyme-linked immunosorbent assay (ELISA), IgG-ELISA, rapid immunochromatographic test, haemmagglutination inhibition (HI) test, and reverse transcriptasepolymerase chain reaction (RT-PCR) as previously reported(3,4). Commercial IgM-capture ELISA and IgG-ELISA (MRL, California, USA) and rapid immunochromatographic test (PanBio, East
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Table: Demographic information of 35 dengue cases No. 1 2 Age, Sex 33, F 29, M Disease day 9 3 7 9 14 6 17 6 13 8 10 13 17 7 8 13 18 9 10 7 8 8 4 5 6 13 4 11 15 19 8 19 Type (PCR) DEN-2 DEN-3 nd DEN-1 nd DEN-3 nd nd nd DEN-1 nd nd nd DEN-1 nd nd nd DEN-1 nd nd DEN-1 nd IgM-ELISA +(1.1)** -(0.3) +(3.2) +(3.6) +(3.7) +(6.7) +(15.4) -(0.2) +(4.0) +(2.7) +(3.8) +(4.1) +(2.2) +(1.5) +(2.3) +(5.2) +(2.5) +(4.4) +(3.8) +(1.7) +(2.8) +(11.3) -(0.8) +(1.4) +(2.2) +(8.2) -(0.5) +(4.1) +(6.9) +(6.7) +(2.2) +(2.4) IgG-ELISA +(7.3) -(0.7) +(3.7) +(4.4) +(5.3) -(0.6) +(3.8) -(0.6) nd +(5.9) +(7.9) +(9.1) +(9.5) +(7.8) +(8.2) +(9.3) +(10.6) +(9.2) +(9.4) +(5.8) +(7.5) +(2.4) +(4.6) +(6.7) +(8.6) +(9.3) -(1.0) +(9.0) +(8.1) +(7.9) +(6.8) +(3.0) Countries of contact Indonesia Indonesia
3 4 5
30, M 30, M 25, F
Thailand Malaysia India Thailand Cambodia
6
49, M
Tahiti
7 8 9 10 11
56, M 53, F 58, M 45, F 23, M
Viet Nam Philippines Philippines Philippines Thailand Cambodia Laos Philippines Thailand Singapore Malaysia Thailand Indonesia Samoa
12 13 14
22, F 44, M 35, F
15
42, M
16
43, M
2 8 14 27 5 12
DEN-1 nd nd nd DEN-1 nd
-(0.9) +(5.0) +(5.2) +(3.4) -(0.3) +(3.6)
-(0.7) +(3.4) +(1.6) +(1.7) +(2.2) +(3.0)
Thailand Cambodia China
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No. 17 18 19 20 21 22 23 24 25 26 27* 28 29 30
Age, Sex 24, F 22, M 26, M 51, M 32, F 24, F 28, F 22, M 26, F 28, F 24, F 19, M 27, M 21, F
Disease day 15 29 5 9 6 13 4 9 8 16 9 23 7 8 4 16 8 23 7 16 10 20 6 16 6 13 5 6 8 2 7 4 7 9 7 29 6 16
Type (PCR) nd DEN-1 nd DEN-2 nd DEN-2 nd nd nd DEN-1 nd DEN-1 nd DEN-1 nd nd nd DEN-1 nd DEN-3 nd nd DEN-1 nd DEN-1 nd DEN-1 nd nd
IgM-ELISA +(4.6) +(3.2) -(0.2) +(2.5) +(2.1) +(3.1) -(0.8) +(4.0) +(3.0) +(3.5) +(3.4) +(2.8) +(3.7) +(6.6) -(0.7) +(7.6) +(5.7) +(8.6) +(4.9) +(7.7) +(1.3) +(1.1) +(4.1) +(6.5) -(0.8) +(5.6) -(0.7) +(2.0) +(3.8) -(0.7) +(6.8) -(0.8) +(5.1) +(8.5) +(4.9) +(7.0) +(14.1) +(18.6)
IgG-ELISA +(1.5) +(1.5) -(0.2) -(0.9) +(1.1) +(1.8) -(0.1) -(0.3) +(1.3) +(1.6) +(1.7) +(1.7) nd -(0.4) -(0.1) +(10.2) -(0.4) +(6.5) -(1.0) +(1.8) +(2.0) +(2.0) -(1.0) +(8.4) -(0.1) +(1.3) -(0.4) -(0.9) +(1.2) -(0.2) -(0.1) -(0.2) +(1.1) +(7.9) +(1.3) +(7.0) +(6.9) +(8.7)
Countries of contact Thailand Cambodia Tahiti Thailand Philippines Cambodia India Thailand Cambodia India Thailand Thailand Philippines Thailand Cambodia Philippines
31 32 33 34 35
25, M 27, F 28, F 25, F 64, M
Thailand Thailand Thailand Thailand Laos Myanmar Thailand
*: secondary infection: not detected nd: not done **: Numbers in parentheses are index values. The values greater than 1.0 were determined to be positive.
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Discussion Dengue virus infection is a serious cause of morbidity and mortality in most countries in the tropical and subtropical areas of the world(8,9). Dengue is considered to be one of the most important infectious diseases in these regions. The cases that we confirmed to be of dengue at our laboratory accounted for only a part of the total imported cases in Japan. Nearly 5 million Japanese visit countries in the tropical and subtropical areas annually, and 2 million people visit Japan from these areas. Therefore, DF/DHF is one infectious disease that should attract more attention in Japan.
Acknowledgement We thank doctors of clinics and hospitals who provided serum samples for the laboratory diagnosis of dengue. This work was supported by grants from Research on Emerging and Re-emerging Infectious Diseases of the Ministry of Health and Welfare, Japan, and from Global Environment Research Coordination System, Ministry of the Environment, Japan, and by the Cooperative Research Grant 2001 (13-A3) of the Institute of Tropical Medicine, Nagasaki University, Japan.
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