Vol.34
No.01
MARCH 2006

Tropical Medicine and Health

Tropical Medicine
and Health

ISSN 1348-8945

Vol.34 No.01 MARCH 2006

ISSN 1348-8945【CONTENTS】
Editorial Note
More attention to the field.
Hirayama K

1

Original articles
Epidemiological study of influenza virus infections in Yangon, Myanmar.
Hasegawa G, Kyaw Y, Nwe HM, Danjuan L, Saito R, Suzuki H, Ebe Y, Cho TM
and Naito M

3

The role of social science research in reducing the burden of tuberculosis
in high HIV prevalence settings
Yanai JN and Ishikawa N

7Proceedings of the 46th Annual Meeting of Japanese Society of Tropical Medicine

15

Vol.34 No.01 MARCH 2006

Tropical Medicine
and HealthJAPANESE SOCIETY OF TROPICAL MEDICINEJAPANESE SOCIETY OF
TROPICAL MEDICINE

Trop.Med.Health日本熱帯医学会表紙!−" ＣＭＹＫ 平島 宮副

背は３mm
（決）

Vol.34
No.01
MARCH 2006

Tropical Medicine and Health

Tropical Medicine
and Health

ISSN 1348-8945

Vol.34 No.01 MARCH 2006

ISSN 1348-8945【CONTENTS】
Editorial Note
More attention to the field.
Hirayama K

1

Original articles
Epidemiological study of influenza virus infections in Yangon, Myanmar.
Hasegawa G, Kyaw Y, Nwe HM, Danjuan L, Saito R, Suzuki H, Ebe Y, Cho TM
and Naito M

3

The role of social science research in reducing the burden of tuberculosis
in high HIV prevalence settings
Yanai JN and Ishikawa N

7Proceedings of the 46th Annual Meeting of Japanese Society of Tropical Medicine

15

Vol.34 No.01 MARCH 2006

Tropical Medicine
and HealthJAPANESE SOCIETY OF TROPICAL MEDICINEJAPANESE SOCIETY OF
TROPICAL MEDICINE

Trop.Med.Health日本熱帯医学会表紙!−" ＣＭＹＫ 平島 宮副

背は３mm
（決）

Tropical Medicine and Health Vol. 34 No. 1, 2006, pp. 1-2
Copyright! 2006 by The Japanese Society of Tropical Medicine

１

Editorial Note

More attention to the field
Kenji Hirayama, M.D., Ph.D.
Editor-in-Chief
Tropical Medicine and HealthJapanese Developments in 2005-2006
In 2005, the Institute of Tropical Medicine of Nagasaki
University (located in Nagasaki, Japan) received two significant governmental grants for the establishment of fieldbased laboratories in Nairobi, Kenya and Hanoi, Vietnam.
At the same time, the Research Institute for Microbial Diseases of Osaka University, Institute of Medical Science of
the University of Tokyo and Research Center for Zoonosis
Control of Hokkaido University received similar grants forthe establishment of overseas laboratories in Bangkok,
Thailand and Beijing, China. Thus, 2005 was a watershed
year for Japan and affiliated countries in initiating longterm research projects aimed at the control of regional aswell as global infectious diseases, such as TB, AIDS, malaria, influenza, dengue fever as well as other emerging andneglected or unknown diseases.
Figure 1 shows the proposed network of researchgroups newly organized by these grants from the Ministryof Education, Culture, Sports, Science and Technology(MEXT), Japan.
Other independent activities supported by the Ministryof Health, Welfare and Labour (MOHL) and the Ministry ofAgriculture and Fishery (MOAF) have been launched tocontrol domestic and imported microbe infections in humans and animals. All of these activities are organized by
the cabinet office of the government.

Global Issues
One important reason for the Japanese government
recognition of infectious disease control as a high-priority
issue stems of course from the endemicity of serious emerging infectious diseases such as HIV, TB, BSE, West Nile fever, SARS, and avian influenza and the threat they pose to
Japanese citizens.
But another reason may be even more compelling.
That is the surprisingly small number of experts and researchers working in this scientific field in Japan. The grave
shortage of human resources is a problem not only for Japan but for all the developed countries, including the UnitedStates and European countries where public health priorities
tend to concentrate in areas such cancer, hypertension,ischemic heart disease and diabetes.
In the past five to ten years, therefore, the fact that developed countries are more concerned than ever about thepossible endemicity of new and old infectious diseases has
been reflected in the G8 summit meetings held in the U.S.
A., Japan and the U.K. During those meetings, malaria, TB,
and HIV/AIDS were recognized as three major diseases
confronting the international community. Now tropical
medicine and international health researchers are expected
to contribute more to solve the problems underlying the endemicity of these infectious diseases.

Figure 1

２

The Responsibility of Researchers
Generally speaking, research is a personal and private
undertaking, and the quality of its outcome is almost totallydependent on individual ability, capacity and the work environment. Without competent personnel, good research cannot be performed, but, recently, the environment of research
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Editorial Policy of “Tropical Medicine and Health”
Peer review and swift publication are our priorities. All
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Figure 2

Tropical Medicine and Health Vol. 34 No. 1, 2006, pp. 3-6
Copyright! 2006 by The Japanese Society of Tropical Medicine

３

EPIDEMIOLOGICAL STUDY OF INFLUENZA VIRUS INFECTIONSIN YANGON, MYANMARGO HASEGAWA１＊, YADANAR KYAW２＊, HLA MYAT NEW３, LI DANJUAN４, REIKO SAITO４,HIROSHI SUZUKI４, YUSUKE EBE５, TIN MAUNG CHO６, and MAKOTO NAITO１
Accepted 14, December, 2005

Abstract: Although influenza is a highly contagious acute respiratory illness of global importance, little is known
about the disease in tropical countries. An influenza survey was conducted in three sentinel sites in Yangon, Myanmar from September 2003 to December 2004. Throat or nasal swabs were collected from 616 patients with
influenza-like symptoms and tested using rapid diagnostic test kits and virus isolation. Influenza B virus was detected in 6 patients from September to October, 2003. Influenza A viruses were detected in 133 patients from Juneto September, 2004, and the 51 influenza A viruses isolated from 72 specimens were all A/H3N2. Influenza virus
infections occurred mainly in the rainy season in Yangon, Myanmar, but continuous ongoing influenza surveillanceis needed.
Key words: influenza, acute respiratory infection, rapid diagnostic test kit, Yangon

INTRODUCTION

MATERIALS AND METHODS

Influenza epidemiology varies according to the geographical location and climate. Influenza occurs mainly
during winter in the temperate zones [1-3]. However, little
is known about the epidemiology and seasonality of influenza in tropical zones, where influenza virus infections occur throughout the year with either no distinct seasonality
or relatively intense activity during the rainy season [4-12].
Myanmar is divided into three areas; upper (northern),
central, and lower (southern) Myanmar. The central andsouthern areas belong to the tropical zone while the northern area belongs to the temperate zone. The average temperature is 25°
C to 33°
C in the cold and rainy season (MaySeptember or October), and 32°
C to 43°
C in the dry season(November-April). The rainfall ranges from 500 mm in thecentral dry zone to 5,000 mm in the coastal regions. Yangon,
the capital city of Myanmar, has a tropical monsoon climate.
No epidemiological study of influenza virus infections
has been conducted in Myanmar to date. We conducted thefirst study in Yangon from September 2003 to December
2004 and clarified the seasonality of influenza virus infections.

Survey on Influenza Virus Infections in Yangon, Myanmar
The respiratory chest unit and pediatric department at
Sanpya Hospital in Yangon were selected as sentinel sites
for the study from September 2003 to December 2004. Two
general practitioners working in the central Yangon alsojoined the study from June 2004.
The patients with influenza-like symptoms who participated in this study presented with a combination ofsymptoms such as fever of more than 38°
C, coughing, rhinorrhea, myalgia, arthralgia, and diarrhea. A standardized
questionnaire was used to obtain demographic data, medical
history, and clinical features for each patient.

１

Virus Antigen Detection and Virus Isolation
Throat or nasal swabs were collected at the first clinic
visit and subjected to influenza A and B virus antigen detection using influenza diagnostic kits (QUICK-S INFLU A/B”SEIKEN”, Denka Seiken Co. Ltd, Tokyo, Japan). The
positive specimens were placed in viral transport media,
and then aliquoted in cryotubes and kept at −80°
C in freezers at Sanpya Hospital for further laboratory examinations.

Division of Cellular and Molecular Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
Chest Medical Unit and ３Pediatric Unit, Sanpya Hospital, Yangon, Myanmar
４
Department of Public Health, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
５
Division of Infection Control and Prevention, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
６
Respiratory Medicine Department, Yangon General Hospital, Yangon, Myanmar*Two authors contributed equally.
２

４

Specimens were transferred in frozen conditions and tested
in the Department of Public Health, Niigata University
Graduate School of Medical and Dental Sciences. Specimens were centrifuged at a low-speed and the supernatants
inoculated into Madin Darby Canine Kidney (MDCK) cells
to observe cytopathic effect (CPE) for influenza viruses.
Type and subtype were determined by hemagglutinin inhibition (HI) tests with type- and subtype-specific antisera
against 2004/05 influenza vaccine strains, such as A/New
Caledonia/20/99 (H1N1), A/Wyoming/3/2003 (H3N2), andB/Shanghai/361/2002 (Denka Seiken Co. Ltd., Tokyo, Japan).

tected in 6 patients (1%) in September and October 2003,
all under 14 years of age. Influenza A viruses were detected
in 133 patients (21.6%) from June to October with a peak inJune 2004 (Fig 1). The majority were under 14 years of age(88.7%), and only two patients were over 60 years of age(Table 1). The sex ratio was 1.42 (men/female).
The clinical symptoms of influenza-positive patients
did not differ from those of influenza-negative patients (Table 2). The clinical diagnosis of patients with influenza-like
symptoms was influenza, bronchiolitis, pneumonia, tuberculosis, respiratory syncytial virus infection, dengue fever,or enteritis.
A total of 72 specimens from the 616 patients tested
with rapid tests were available for further virological examinations, and influenza viruses were isolated from 51 specimens (70.8%). All of these isolated strains were antigenically similar to A/Wyoming/3/2003 (H3N2), but not to A/
New Caledonia/20/99 (H1N1) or B/Shanghai/361/2002.

RESULTSA total of 616 patients were tested with rapid diagnostic test kits during the study period, and none had a history
of influenza vaccination. In 90% of patients, throat or nasal
swabs were collected within the first 3 days after the onsetof symptoms.
Among the 616 patients, influenza B viruses were de-Fig. 1. Number of influenza test positive patients per week, 2003-2004

Table 1. Age distribution and percentage of influenza patients.
age
0-4
5-9
10-14
15-19
20-59
60ND
total

type A79 (59.4)
33 (24.8)
6 (4.5)1 (0.8)12 (9.2)
2 (1.5)0133 (100%)

type B
2 (33.3)
3 (50.0)
1 (16.7)0000
6 (100%)negative
324 (67.9)
45 (9.4)
18 (3.8)
12 (2.5)64 (13.4)
10 (2.1)
4 (0.8)477 (100%)

ND: No data of age. Numbers in bracket are percentages.

total
405 (65.7)
81 (13.1)
25 (4.1)
13 (2.1)
76 (12.3)
12 (1.9)
4 (0.6)616 (100%)% (positive)
20.0%
44.4%
28.0%
7.7%
15.8%
16.7%
0.0%
22.6%

５

Table 2. Clinical symptoms of influenza virus positive and negative cases
Clinical symptoms
fever (>38 °C)
coughrhinorrhea
myalgia
arthralgia
diarrhea

Influenza viruses
Positive cases
Negative cases
100%
95.5%
97.0%
31.6%
9.8%
12.8%

100%
96.0%
88.7%
28.0%
16.1%
16.9%

DISCUSSION
We conducted a sentinel surveillance of influenza virus
infections in Yangon city from September 2003 to December 2004 and detected influenza B viruses at the end of therainy season (Sept-Oct) in 2003 and influenza A viruses in
the rainy season (June-Oct) in 2004.
Influenza virus infections are more common in winterin temperate countries but vary in tropical countries [6-12].
It has been noted that influenza viruses survive more readily
in aerosols under conditions of low temperature and low humidity [13, 14]. These conditions coincide with the mechanism of seasonality of influenza in temperate countries, but
the correlation is not clear in tropical countries. In tropicalcountries such as Thailand, Singapore and Indonesia, influenza viruses are detected throughout the year with one or
two peaks depending on the study year, but there is not always a correlation between rainy seasons and peaks of influenza virus infections. In Singapore, no correlation has
been found between influenza activity and climatic conditions or influx of travelers [10]. Mortality from influenza isprobably greatly underestimated or not even reported inthese regions because of the lack of good surveillance programs in many tropical countries. Our study in Yangon wasa preliminary study of only one year in duration. Thus, further long-term studies in Yangon and other areas should be
important additions to the epidemiology of influenza intropical areas.
Between October 2003 and September 2004 in theneighboring country of Thailand, influenza B and A (H3)viruses co-circulated, the former predominating in 2003 andthe latter in 2004 [4, 5]. Our study was insufficient in termsof subject number and study period, but the epidemiological
data from these two countries was quite similar. In 2004, influenza A/H3N2 viruses predominated in Yangon as inmany countries [4, 5]. Most of these isolated strains were
antigenically similar to A/Wyoming/3/2003 (H3N2), a component of the 2004/2005 influenza vaccines recommended
by WHO. They belonged to A/Fujian-like strain, which had
circulated in Asia since 2002 and caused major epidemics

worldwide in the 2003/2004 winter [4, 5]. Since virologicalsurveillance is quite limited in tropical areas includingSoutheast Asian countries, the epidemiological study in
Myanmar is important to global influenza surveillance. In
our study, the rapid test-positive samples obtained in Myanmar were sent to Japan for virus isolation, and viruses wereisolated from approximately 71% of the samples, suggesting that this manner of international collaborative study,
though perhaps not ideal, is a viable option for participationin the WHO influenza surveillance network.
The clinical symptoms of influenza-positive patients
did not differ significantly from those of influenza-negative
patients in this study. The lack of differential diagnosis
sometimes leads to misdiagnosis and the misuse of antibiotics. Therefore, the development and application of affordable test kits to detect pathogens other than influenza may
also be helpful for the diagnosis of febrile diseases in tropical countries.

ACKNOWLEDGMENTS
We thank Denka Seiken Co. for providing the QUICKS INFLU A/B “SEIKEN”. This work was supported in partby Grants-in Aid for Scientific Research (A) and (B).

REFERENCES
１．Nicholson KG, Wood JM, Zambon M (2003) Influenza.
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２．Suzuki H, Saito R, Masuda H, Oshitani H, Sato M, Sato I(2003) Emergence of amantadine-resistant influenza A viruses: epidemiological study. J Infect Chemother 9: 195200.
３．Saito R, Oshitani H, Masuda H, Suzuki H (2002) Detectionof amantadine-resistant influenza A virus strains in nursing
homes by PCR-restriction fragment length polymorphism
analysis with nasopharyngeal swabs. J Clin Microbiol 40:
84-8.
４．WHO (2003) Influenza in the world. Weekly Epidemiological Record 78: 393-396.
５．WHO (2004) Influenza in the world. Weekly Epidemiological Record 79: 385-392.
６．Takeuchi Y, Nakamura K, Nakayama M, Kupradinunt S,
Nishikawa F, Suzuki H, Takahashi M, Yamazi Y, Takahashi
K, Pongprot B, Supasert S, Supawadee J, Vithayasai V,
Damrongsak D (1989) Isolation of influenza virus in Thailand in the rainy seasons of 1986, 1987 and 1988. J Nippon
Medical School 56: 201-203.
７．Besselaar TG, Botha L, McAnerney JM, Schoub BD(2004) Antigenic and molecular analysis of influenza A (H
3N2) virus strains isolated from a localized influenza outbreak in South Africa in 2003. J Med Virol 73: 71-78.
８．Centers for Disease Control and Prevention (CDC) (2004)

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Update: influenza activity--United States, 2003-04 season.
MMWR 53: 284-287.
９．European Influenza Surveillance Scheme (2004) Low levels of influenza activity in Europe. EISS-Weekly Electrical
Bulletin. http://www.eiss.org/index.cgi. 120: 3.
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０．Hampson AW (1999) Epidemiological data on influenza in
Asian countries. Vaccine 17 Suppl 1: S19-23.
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１．Shek LP, Lee BW (2003) Epidemiology and seasonality of
respiratory tract virus infections in the tropics. Paediatr
Respir Rev 4: 105-111.
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２．Beckett CG, Kosasih H, Ma’roef C, Listiyaningsih E, El-yazar IR, Wuryadi S, Yuwono D, McArdle JL, Corwin AL,
Porter KR (2004) Influenza surveillance in Indonesia: 1999
-2003. Clin Infect Dis 39: 443-449.
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３．Hemmes JH, Winkler S, Kool SM (1960) Virus survival asa seasonal factor in influenza and poliomyelitis. Nature
188: 430-431.
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４．Shaffer L, Soergel ME, Straube DC (1976) Survival of airborne influenza virus: effects of propagating host, relative
humidity and composition of spray fluids. Arch Virol 51:
263-273.

Tropical Medicine and Health Vol. 34 No. 1, 2006, pp. 7-13
Copyright! 2006 by The Japanese Society of Tropical Medicine

７

THE ROLE OF SOCIAL SCIENCE RESEARCH IN REDUCING THE
BURDEN OF TUBERCULOSISIN HIGH HIV PREVALENCE SETTINGS

Jintana Ngamvithayapong-Yanai１，２ and Nobukatsu Ishikawa１
Accepted 23, January, 2006

Abstract: Tuberculosis (TB) is a global public health problem. The HIV/AIDS epidemic negatively affects tuberculosis control in many countries. The United Nations has set the Millennium Development Goals (MDGs) aiming
to halve TB prevalence and mortality by the year 2015. In this paper, the authors summarize the global situation of
TB associated with HIV/AIDS (TB/HIV), WHO’s interim policy on TB/HIV, as well as the status and needs of social science research. The authors reviewed two major social interventions which are critical for TB control in HIV
high prevalence settings, namely those to reduce stigma and those to promote adherence to TB/HIV medication.
The review suggests that more social science research should be implemented in resource limited countries.
Key words: tuberculosis, HIV/AIDS, TB/HIV, social science research, social interventions“The battle against AIDS will not be won unless the international community does more to fight TB as well”.
Nelson Mandela, former president of South Africa and former tuberculosis patient
The 15th International AIDS Conference, Bangkok, Thailand,
15 July 2004
Why does fighting AIDS need to involve fighting TB?
HIV/AIDS and tuberculosis (TB) are the world’s firstand second leading causes of death from infectious diseases.
If there had been no HIV epidemic, TB would have been
controlled. In 2005, it is estimated that about 40.3 million
adults and children were living with HIV and about 3.1 million have died from AIDS [1]. About8.8million new casesof TB occurred in 2003 with an estimated 1.7 million dying
from the disease. In the same year, about 674,000 new casesof TB were associated with HIV (TB/HIV), and 229,000
people with HIV/AIDS (PHA) died from TB [2]. Tuberculosis is the leading cause of morbidity and mortality among
PHA. At least one in three will develop TB [3]. The alarming global crisis of HIV/AIDS and TB has prompted theUnited Nations and the international community to set a
global target to reduce these priority diseases. The Millennium Development Goals (MDGs) aim to reverse the incidence and halve the mortality of these two diseases by theyear 2015 [4].
１Biologically, it is well known that TB enhances HIV
replication and accelerates HIV progression, thereby shortening the life expectancy of PHA [5]. The close interaction
between TB and HIV/AIDS indicates the need to reduce theburden of both HIV/AIDS and TB. Most Sub-Saharan African countries with high HIV prevalence have suffered thenegative impact of the interaction between HIV/AIDS and
TB for more than a decade. WHO recently published thefirst interim policy on collaborative TB/HIV activities totackle the dual epidemics [6]. Table 1 presents the WHO’s
recommended interventions to reduce the burden of TB and
HIV/AIDS. The biomedical interventions to reduce TB andHIV burden include antiretroviral therapy (ARV) and cotrimoxazole preventive therapy (CPT) for HIV-positive TB
patients and isoniazid (INH) to prevent TB among PHA.
The results of clinical research show that CPT can prolong
lives and ARV can reduce death among HIV-positive TB
patients [7-10]. INH can reduce the risk of developing TBamong PHA [11]. Despite the efficacy of these medical interventions, the task of reducing the TB/HIV burden inresource-limited settings is a great challenge and necessitates interventions suggested by social science research.

The Research Institute of Tuberculosis, Japan Anti-TB Association, Tokyo, Japan
TB/HIV Research Foundation, Chiang Rai, Thailand.

２

８

Why social science research?
To control the epidemic of TB and HIV/AIDS, wemust not only deal with the HIV virus and the TB bacteria
but also manage patients who carry these germs and educate
the health worker who deliver health services to the population. Human behavior and social environments are complicated, and biomedical interventions alone are not sufficientfor disease control. It has consistently been proposed that
TB and AIDS are social diseases whose patterns of transmission must be understood, not only through the clinicalor laboratory studies of bacteria and virus, but also throughthe study of attitudes, behavior and social organization [1219]. In particular, HIV/AIDS provides a tragic example of acomplex interactions between the disease agent and humanbehavior, which further complicates the effort to control tuberculosis. How can social science research contribute to
TB prevention and care in high HIV prevalence settings?
Based on the social science research in the northern-most province of Thailand where HIV epidemic fuels theTB epidemic (HIV prevalence among pregnant women was
3.7% and TB incidence was 140/100,000), we summarized
the psycho-social interactions between HIV/AIDS and TB
and the negative impact on TB and HIV/AIDS prevention
and care (table 2) [20]. It is noteworthy that this social science research was carried out before ARV was available tothe poor people of Thailand. Increased access to antiretroviral therapy among people with AIDS in Thailand and otherresource-limited countries might reduce AIDS related fatalism and stigma [21, 22]. But even though several high HIV
prevalence countries in sub-Saharan Africa successfully
mobilized free ARV for poor patients, stigma and discrimination, especially among women resulted in a low level ofparticipation in HIV testing and access to ARV. Gender inequality is such that a poor woman is placed in an evenworse social situation if her husband or in-laws becomeaware of her HIV status [1]. These complicated circum-

Table 1: Interventions to reduce the burden of TB and HIV/AIDS recommended
by the World Health Organization [6]A. Interventions for collaboration between TB and AIDS programs
A.1. Set up a coordinating body for TB/HIV activities effective at all levels
A.2. Conduct surveillance of HIV prevalence among tuberculosis patients
A.3. Carry out joint TB/HIV planning
A.4. Conduct monitoring and evaluation
B. Interventions to decrease the burden of tuberculosis in people living with HIV/AIDS
B.1. Establish intensified tuberculosis case-finding
B.2. Introduce isoniazid preventive therapy
B.3. Ensure tuberculosis infection control in health care and congregate settings
C. Interventions to decrease the burden of HIV in tuberculosis patientsC.1. Provide HIV counseling and testing
C.2. Introduce HIV prevention methods
C.3. Introduce co-trimoxazole preventive therapy
C.4. Ensure HIV/AIDS care and support
C.5. Introduce antiretroviral therapy

Table 2: The psycho-social interactions between HIV/AIDS and TB and the negative impact on TB and HIV/AIDS prevention and care in Thailand (before a lunching the government’s policy on access to ARV in 2003) [20, 22,
33-35]
Psycho-social interactions between HIV/AIDS and TB!The social stigma attached to HIV/AIDS is enormous and results in denial of HIV testingand delay in access to TB and HIV care
!Serious AIDS stigma and an inadequate knowledge about TB symptoms results in delays
in seeking TB care because TB symptoms are comparable to AIDS and people with TB
symptoms were afraid of HIV/AIDS!Most HIV negative TB patients were stigmatized as having AIDS.
!The high mortality among HIV-positive TB patients during TB treatment discredited the
TB treatment efficacy. Health staff had a low motivation to care for the patients because
the treatment results were so discouraging.
!Fatalism attached to HIV/AIDS hindered the patients access to health carepatients felt hopeless and lacked the motivation to adhere to their TB treatment.

９

Table 3: List of some interventions to reduce TB and HIV/AIDS stigma and desired outcomes [36-40]
Interventions to reduce stigma

Desired outcomes

Mass communication interventions
Television, radio, newspaper or poster presenting the followings:- photos and news of countries’ leaders or popular persons
telling about their experiences of having TB or
HIV/AIDS; showing close embrace with patients; showing
acceptance for HIV blood testing; showing TB is curable or
showing that they are surviving from HIV/AIDS- photos and news of Miss HIV/AIDS stigma contest- increase public’s acceptance and reduce discrimination- promote early HIV testing- reduce delay in seeking care

Training/workshop-Intensive training course to reduce stigma among health workers-Community awareness-raising through participatory training-Involving HIV-positive long-term survivors in education and training-improve health workers’ attitude
towards TB and AIDS patients and willingness tocare for them.
-increase HIV testing and access to careCounseling-Individual or family counseling by health workers or by HIV-positive counselor-reducing self-stigma; reduce anxiety and stress; disclosure HIV to spouse and family members

Social mobilization and community participation-Establishing network (self-help group) of PHA and motivate PHA to join the network-Financial assistance to PHA and family-Involving PHA, religion leaders and community leaders in policy making, and in
the development and implementation of programs.

-reducing self-stigma-empowering PHA-increasing HIV testing and disclosure of HIV status

Improving health service system and promoting access to treatment-Free and effective treatment-Integrating HIV/AIDS care with other chronic diseases clinics-PHA-Friendly hospital-increase access to HIV care-increase HIV testing-reduce discrimination feeling

Law and regulation intervention- Law or regulation against stigma in general- Law or regulation for the work places- Code of professional ethics/code of practice- Standard or universal guidelines- protection of patients’ right- patients are eligible for petition the court and receive support for complaint due to stigma.

Table 4 Scope of adherence to medication in TB/HIV care [41]
Scope of adherence
to medication in TB/HIV care

Targeted HIV-positive person

Expected healthoutcome ofgood adherence

Potential negative impact of
non-adherence

Adherence to TB preventive
Therapy

HIV-infected persons with latent
TB infection (no clinical TB
symptoms)- Reducing risk to
become sick with TB- drug resistance

Adherence to TB treatment

HIV- positive TB patients(having TB symptoms)-cure from TB and do
not transmit TB to others-death-treatment failure-drug resistant-continue transmitting
TB to others

Adherence toantiretroviral therapy(ARV)

AIDS patients(usually CD4 < 200cells/mm３)-prolong life, better
quality of life
-avoid opportunistic infection-reduce risk of HIV
transmission-drug resistant-treatment failure-death１０

Table 5 Interventions for improving adherence to medication [13, 20, 42-44].
Interventions for enhancing adherence to medication
Improving health service systems-Eliminating or lowering user fees
-Providing directly observed therapy (DOT)-Organizing service hours convenient for patients and minimizing waiting time
-Active follow-up system for non-adherent patients-Offering health education and counseling service by using linguistically and culturally appropriate messages.
-Hospitalization may prevent non-adherence among patients exhibiting the profile of defaulter (e.g. homeless, alcoholic patients)-Involving people with HIV/AIDS network and community leaders in delivery services(e.g. providing medication education, follow up non-adherent cases, home visit)
Improving attitude and performance of health care providers-Good relationship between health providers and patients significantly improves patient adherence.
-The providers should render service with courtesy and respect for patients.
-The providers should understand patients’ needs and constraints, understand patients’ cultural differences in attitudes to disease.
-The providers should spend more time listening to patients.
-Giving rewards to health provider who achieve high adherence rate
Facilitating patient medication-Providing special packages of medicine such as a daypack for easier medication.
-Prescribing medication once a day and fixing a time such as before breakfast or before bed.
-Providing several medicine reminding system (alarm clock, calendar, reminding through pager or cell phone, linking medication time todaily life activity)
Providing incentives to patient and community-Providing transportation support to attend clinics, shelter support for homeless people, offering meals and assistance with job skills forpoor patients-Giving rewards to patients who adhere well to the treatment.
-Paying a deposit at the start of their treatment, which entitles the patient to cheaper drugs and is refundable on good adherence to prescribed course.

Table 6 Literature on social science research in TB in comparison with AIDS
cited by the National Library of Medicine (NLB) website [26].
Searching keywords...... AND TB...... AND AIDS

TB
(no. of papers)

AIDS(no. of papers)

1837
4
13
4
137
31

25,028
515
141
132
1007
433

Social sciences AND
Behavioral research AND
Qualitative research AND
KAP AND (Knowledge, Attitude, Practice)
Poverty AND
Stigma AND

Table 7 Study topics and geographic location of tuberculosis behavioral
and social science research (n=175) [45]Research settings-USA-based-International-based-Non-location specific (e.g. concept, position papers)

47%
36%
17%

Study topics-Patient adherence-Social, cultural factors (including Knowledge-Attitude-Belief)-Structural influences-Health seeking behavior-Provider adherence-Others

47%
45%
33%
19%
14%
12%

１
１

stances require social science research to identify sociallyand culturally sensitive behavioral interventions.
UNAIDS and WHO identify stigma and adherence tomedication as the major challenges in controlling the HIV/AIDS epidemic [1, 23]. In this article, we discuss two majorsocial and behavioral interventions, namely interventions to
reduce stigma (table 3) and interventions to promote adherence to TB/HIV medications (table 4, 5). These two social
interventions are important prerequisites for implementing
the medical interventions recommended by WHO (table 1).
For example, interventions for reducing AIDS stigma canfacilitate HIV testing for TB patients, and interventions forenhancing adherence are important to ensure treatment efficacy and to prevent drug resistance when patients receive
ARV, CPT and INH.
Status of social science research in TB and TB/HIV
In 1975, the Special Program for Research and Training in Tropical Diseases (TDR), a globally coordinated effort of the United Nations Children’s Fund (UNICEF),
United Nations Development Program (UNDP), WorldBank and World Health Organization (WHO), was established to combat neglected tropical diseases and diseases ofthe poor and disadvantaged [24]. In view of the importanceof research in social sciences to control communicable diseases, TDR started supporting social science research in1979. However, social science research for tuberculosis is
still quite new to TDR, as shown by the fact that TDR
added tuberculosis to the tropical disease portfolio only in1999 [25]. Table 6 clearly shows that TB has received muchless attention from social science researchers in comparison
to HIV/AIDS. According to the United States National Library of Medicine (the world’s largest literature database for
medical and public health research), the number of TB social science research articles in scientific journals is 7 to
128 times less than HIV/AIDS articles [26]. Obviously, social science research in HIV/AIDS has received ample recognition because results of this research help to identify interventions to reduce the HIV/AIDS burden [27]. However,
the role of social science research in improving TB care, especially in developing countries, is oddly limited for suchan old disease as TB. A recent review of the 175 social science articles on TB (table 7) shows that half of the studies
were conducted in the United State (Rawls and Booker,
2005), although 95 percent of global TB cases and99percent
of TB deaths occur in the developing world [2]. Clearly,
therefore, it is imperative that more social science research
be conducted in high burden and resource-limited countries.
The difficulty of achieving the global target for TB
control is mainly due to the lack of human resources andqualified staff [28]. At the global level, the published infor-

mation on human resources and TB control are limited andalmost none relate to HIV-TB control [29]. Training is essential to the development of a health workforce geared to
TB control, but regular international TB training courses areorganized by a limited number of organizations [30, 31].
Most international training courses focus on clinical orlaboratory training and the management of tuberculosis programs. To our knowledge, none of these courses include social science subjects in the training curriculum, except theinternational courses organized continuously by the Research Institute of Tuberculosis (RIT) Japan Anti-TB Association (JATA) since 1963. The RIT has incorporated social
science subjects into the training curriculum for TB program managers from the start of training on the basis of theview that clinicians and TB program managers should apply
a broader and more holistic perspective to TB services and
TB programs. Currently, social science topics include concepts and practical examples about community beliefs andperceptions, social stigma, health systems and healthseeking behavior, gender, adherence to treatment, community participation and interpersonal communication skills.
These topics are relevant to WHO’s newly recommended
Stop TB Strategy for achieving the MDGs [2].

CONCLUSION:
HIV/AIDS biologically and socially interacts with TB.
Reducing TB associated HIV burden requires both biomedical and social interventions. The current involvement of social scientists in research and training for TB control in highHIV prevalence settings is limited. To facilitate the Millennium Development Goal for TB, social science research andtraining should be implemented in countries which are affected by these dual epidemics. Social science research canpromote understanding regarding the complex psychosocial interplay of TB and HIV/AIDS. In addition to addressing these problems, social science research can help toidentify the interventions which are effective in urging vulnerable patients, including women and the poor to take advantage of TB/HIV prevention and care services. Social science research should show how to implement these interventions on a large scale and how to influence national policy and care strategy [2,27,32]. The training courses designed for TB and HIV/AIDS program managers and service providers should include social science subjects to ensure that the program and services are responsive to thecomplicated biological and the psycho-social interactions of
TB and HIV/AIDS.

１
２

ACKNOWLEDGEMENT:The field research in Chiang Rai, Thailand (19952005) was supported by the Japanese Foundation for AIDS
Prevention (JFAP) and the research grants from Japanese
Ministry of Health, Welfare and Labor. Japan Society for
the Promotion of Science (JSPS) supports the fellowship for
the first author.

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Tropical Medicine and Health Vol. 34, No.1, 2006, pp. 15-66

PROCEEDINGS OF THE 46TH ANNUAL MEETING OF
JAPANESE SOCIETY OF TROPICAL MEDICINE
14-15 October 2005, Kyoto

President
Naoki Arizono, M.D, DMSc
Professor
Department of Medical Zoology
Kyoto Prefectural University of Medicine
Contents
Special lecture
Trend of Japanese Foreign Aid in Education−Implication from Afghanistan Activities−

Utsumi, S.

Prize Winner’s lectures
The JSTM Award of Excellence
An Endeavor Study in Laboratory to Field −A personal history, which passes through a research and eradication
against onchocerciasis and leishmaniasis−
Nonaka, S.
JSTM Young Investigator’s Award
The mechanisms of thrombocytopenia in the acute phase of secondary dengue virus infections
Saito, M.
Symposium 1 The dawning of travel medicine and immigrant medicine
S1-1
Introduction
Nishiyama, T.
S1-2
Migrant medicine in travel medicine
Kimura, M.
S1-3
Recent tendency of immigrant medicine at hospitals of Shiga prefecture and Japan
Ida, T.
S1-4
Problems accompanied with accepting foreign patients in small medical facilities in Japan
Kobayashi, Y.
S1-5
Current problems and future solution in medical interpretation/transplation in Japan
Muraji, T.
S1-6
Report on the Present Status of the Medical Interpreter Dispatch System Pilot Project in Kyoto, Japan
Takashima, A.
Symposium 2 Medical Cooperation from Japan to Africa in the21st century
S2-1
Introduction
Ohta, N.
S2-2
Japan’s contribution in achieving the health MDGs−“Health and Development Initiative (HDI)”− Yamamoto, T.
S2-3
Present Situation of AIDS/HIV Infection and Anti-retroviral treatment (ART) in Zambia: JICA
HIV/AIDS and TB Project in Zambia
Mizutani, T
S2-4
The prospects for the malaria control, using by home based and school based approach, in Africa
Kobayashi, J.
S2-5
The role of community health worker in infectious disease prevention in Senegal
Shiina, C.
S2-6
Prevailing Essential Medicines in Africa
Kimura, K.
Symposium 3 The role of laboratory in international cooperation in the field of tuberculosis and HIV control
S3-1
Introduction
Osuga, K.
S3-2
TB/HIV field research activities in Chiang Rai, Thailand
Yamada, N.
S3-3
A molecular analysis of tuberculosis infection in Zambian prisonsMitarai, S.
S3-4
HIV seroprevalence survey among TB patients in Cambodia (2003 and 2005)
Yoshihara, N.
S3-5
Where are going Laboratory projects in developing countries?- The case of HIV/AIDS & TB control
project in ZambiaWakasugi, N.
Symposium 4 What are vectors? How should we control them?
S4-1
Introduction

Takagi, M.

１
６

S4-2
S4-3
S4-4
S4-5

Life history adaptation and transmission of human diseases in mosquitoes
African malaria vectors and their recent studies
Intermediate host snail of schistosomiasis
Vector ecology and preventive strategy for tick-borne emerging/reemerging diseases in Asia

Tsuda, Y.
Minakawa, N.
Noda, S.
Takada, N.

Workshop C-1 Research development in the molecular biology and molecular pathology of protozoan infections
14C-01 The splenomegaly of NC/Nga mice infected with Plasmodium berghei.
Oikawa, Y.
14C-02 Gene conversion and extensive polymorphism of the RhopH1/Clag family members in Plasmodium
falciparum
Iriko, H.
14C-03 Structure and expression analysis of a multigene family of Gp82 of Trypanosoma cruzi
Dujdow, S.
14C-04 Crystal Structure and Catalytic Mechanism of Trypanosoma cruzi Dihydroorotate Dehydrogenase
Inaoka, D.K.
14C-05 Mutational analysis of trypanosome alternative oxidase (TAO) as a potential target for
trypanosomiasis chemotherapy
Nakamura, K
Miyahira, Y.
14C-06 Roles of CD8＋ T cells for achieving the control of Trypanosoma cruzi infection
14C-07 Development of two-step DNA vaccines targeting the liver-stage malaria parasites based on theubiquitin-proteasome system
Himeno, K.
14C-08 Signaling molecules responsible for the excystation and metacystic development of Entamoeba
invadens
Makioka, A.
14C-09 Posttranslational lipid modification of Rab proteins by a protein geranylgeranyltransferase type IIfrom Entamoeba histolytica
Makioka, A.
Workshop C-2 Problems of malaria treatment and search for new antimalarial drugs
14C-10 Artesunate-Amodiaquine combination therapy in Utan, Sumbawa, Indonesia
Kanbara, H.
14C-11 New antimalarial endoperoxide mechanism of action and development of resistance using Plasmodium
falciparum, in vitro
Nagwa, S.M.A
14C-12 New antimalarial drug development−antimalarial activity and pharmacokinetics of endoperoxide−
Nakase, Y.
14C-13 A consideration to mechanism of anti-malarial drug action and drug resistance construction
Miyata, Y.
14C-14 Analysis of mutations in cytochrome b gene of Plasmodium falciparum isolates in Thai-Myanmar
borderNaoshima-Ishibashi, Y.
14C-15 Screening for G6PD deficiency by WST-8 method (2): reactivity of blood-spotted filters collected in
malaria endemic countries
Arai, M.
Workshop D-1 Present status of viral and bacterial infections in Asia
14D-01 Distilling clusters from the statistics of dengue in Vietnam using a kriging interpolation approach
Tanimura, S.
14D-02 Molecular epidemiology of dengue virus serotype 2 in the Philippines
Salda, L.T.D.
14D-03 Genetic analysis for susceptible gene to Dengue Hemorrhagic Fever in Vietnam
Nguyen, T.P.L.
14D-04 Seroepidemiological study on HBV, HCV and HIV infections among voluntary blood donors in Lao PDRToriyama, K.
14D-05 Inter-CRF recombinants (ICRs): Discovery of new class of HIV-1 recombinants and its epidemiologicalimplications
Takebe, Y.
14D-06 Possible risk of Salmonella infection from market foods in Vientiane Capital, Lao PDR
Midorikawa, Y.
14D-07 Prevalence of respiratory infection caused by Streptococcus pneumoniae and Haemophilus influenzae
in the camps of Tsunami affected area in Sri Lanka
Watanabe, H.
14D-08 Phenolyc glycolopid-1 (PGL-1) in tissues infected by Mycobacterium ulcerans
Shimizu-Suganuma. M.
Workshop D-2 Epidemiology and Control of arthropoad-borne protozoan infections
14D-09 Latent infection of malaria parasites in school children living in the endemic aria in Vietnam.
14D-10 School based malaria education in Mekong sub-region
14D-11 Prevalent distribution of Kobe-SSUrDNA-type- Babesia microti in rodents in the southern part ofMainland of China as well as Taiwan

Nakazawa, S.
Kobayashi, J.
Saito-Ito, A.

１
７

14D-12
14D-13
14D-14
14D-15

Identification of Causative Parasites of Leishmaniasis in Pakistan by Chytochrome b Gene Analysis
Uezato, H.
Prevalence of Leishmania donovani specific urinary antibody in a community in Bangladesh Islam Mohammad, Z.
Epidemiological studies on human cutaneous leishmaniasis in Sri Lanka
Sanjoba, C.
Neem oil as biological control against Phelebotomine sandfly
Wagatsuma, Y.

Workshop C-3 Pathogenesis of helminthiasis
15C-01 Preliminary studies on the effect of T cell- and inflammatory cytokines on mucin-related gene
expression in intestinal epithelial cells
15C-02 Mechanism of mucosal protection against nematode infection: altered expression of goblet cell- andmucin glycosylation-related genes in the intestinal epithelium in rat.
15C-03 Protective immunity against H. nana oncosphere is established independent to known apoptosis
regulatory molecules.
15C-04 Schistosomiasis haematobia: Difficulty of Urination

Takeda, K.
Yamauchi, J.
Onishi, K.
Aoki, Y.

Workshop C-4 Present status of helminthiasis in Asia
15C-05 Usefulness of urine-ELISA which detects filaria specific IgG4: a survey in Jianxi, China
Itoh, M.
15C-06 Intestinal parasitic infections in school children in a suburban area of Hanoi, Vietnam
Uga, S.
15C-07 Study on transmission and infection of soil-transmitted nematode in the suburb of Hanoi, Vietnam:
contamination of water and air with parasite eggs
Noda, S.
15C-08 Study on the intestinal parasite infection among school children in Luangprabang Province, LAO P.D.R
Yamamoto, K.
15C-09 Study for Mebendazole in Lao PDR
Ishida, T.
15C-10 Paragonimiasis in Lao PDR
Habe, S.
Workshop D-3 Research development of malaria transmission-blocking transgenic-anopheline mosquitoes
15D-01 Measurement of xanthurenic acid in Anopheline mosquito
Hattori, R.
15D-02 Relationship between malaria transmission efficacy and the amount of xanthurenic acid in Anophelinemosquito
Yoshida, H.
15D-03 Robust expression of a foreign gene in the salivary glands of Anopheline mosquitoes
Watanabe, H.
15D-04 Transgenic Anopheline mosquitoes expressing lectin form marin organism impaire in transmission of amalaria parasite
Shimada, Y.
Workshop D-4 How to counter imported tropical diseases in Japan
15D-05 A review of the seminars for tropical medicine and hygiene in Kinki Region
Kaku, T.
15D-06 The trend of new HIV infections and patients in Saku central hospital
Takayama, Y.
15D-07 Summary and Problems of Training Course for Diagnosis of Opportunistic Protozoan Infections
Associated with AIDS
Takeuchi, T.
15D-08 Simulations on SARS outbreak in Japan using the mathematical model
Fukutome, A.
15D-09 Travel Medicine of General Practice in Japan
Hitani, A.
15D-10 How well Travel Clinics are known among Travel Agencies
Fukushima, S.
15D-11 Chemoprophylaxis according to the guidelines on malaria prevention for Japanese overseas travelers
Mizuno, Y.

１８Special lecture
TREND OF JAPANESE FOREIGN AID IN EDUCATION−IMPLICATION FROM AFGHANISTAN ACTIVITIES−SEIJI UTSUMI
Graduate School of Human Science, Osaka University

The turning point of educational foreign aid was World
Conference of Education For All 1990 held in Thailand.
EFA 2000 in Dakar and UN millennium Goals are refrain of
EFA 1990. The EFA conference showed us the serious situation of education in developing countries.
The meaning of this conference is that the universal
basic education becomes political goal from the ideology ofeducation. After the EFA conference international aid went
to the basic education field. The Japanese policy for educational aid mentioned in the JICA report of ’Development
and Education’ in 1994. There are 3 basic policies such as
educational aid should be increased up to 15% of bilateral
ODA, basic education should be main target, educational
ODA should have well-balanced in all educational sectors.
1996 OECD-DAC announced the new policy paper ofODA, which were included educational goals. The DAC paper mentioned EFA goal should be cleared year 2015 andgender gap should be abolished up to year 2005. For clear
these goals, MOF and JICA make the new educational policy paper which were included the making integrated developing plan with educational sector is needed.
Japanese government takes the initiative of Afghanistan reconstruction process includes education. Japanese
educational support for Afghanistan had some different
points comparer with before. Afghanistan aid had not only

the development aid but also the emergency and the reconstruction activities. The Ministry of Education Japan took
some initiative for implementing the activities with MOFA.
Now, Education Aid is 1 (one) billion US$ and 10% of
total ODA (2002). This amount includes Yen loan andscholarship for foreign students. Technical cooperation of
JICA educational budget is 30 billion yen and 20% of total
JICA budget. JICA activities divide basic education vocational training and higher education one third each other.
After Afghanistan aid, Japanese foreign aid extends
development aid to emergency and reconstruction. It means
scheme, process and actor extend also. Ministry of Education, Universities and NGOs are new actor of this field. But
they are not main actor yet. But now education is one of themain stream of ODA. Especially reconstruction stage ofpoet-conflict countries education is the most important fieldof support.
Therefore the following items are needed for the better
educational aid.
Quality assurance of aid
Coordination and closer relation between various actors
Making comprehensive approach
Making system for emergency situation
Human development for educational aid

１
９Prize Winner’s lectures
The JSTM Award of Excellence
AN ENDEAVOR STUDY IN LABORATORY TO FIELD−A PERSONAL HISTORY, WHICH PASSES THROUGH
A RESEARCH AND ERADICATION AGAINST ONCHOCERCIASIS AND LEISHMANIASIS−SHIGEO NONAKA
Division of Dermatology, Department of Organ-Oriented Medicine, Faculty of Medicine,
University of the Ryukyus, Okinawa, JapanMy concerned respected professor in dermatology, andparasitology was Dr. Michio Nogita, and Dr. Daisuke
Katamine respectively. Their special interest in the field ofstudy was the same origin, and actually they were the disciple followers of Dr. Seiichi Kitamura. Dr. Katamine was analumni member of dermatology in Nagasaki university
school of Medicine. My medical graduation was completed
on 1965, and then served a rotating internship at Nagasaki
university hospital for one year. After that, I got chance toget speciality training in the department of dermatology ofNagasaki University. During this period, Professor Nogita
arranged all possible facilities for my training in dermatology, and Professor Katamine always encouraged me in all
purposes to acquire knowledges. As a result, I entered into
the postgraduate course, and carried out a biochemical
study on acne vulgaris. After completion of my postgraduate course, the clinical training was carried out in dermatology clinics. My research exposure in the field of tropical
medicine begun in a project for eradication of onchocerciasis in Guatemala, which was started by Dr. Isao Tada since
7th decade of 20 century. I was engaged to acquire knowledge and experiences in a several subjects from this project
not only dermatological, but also parasitological, epidemiological and entomological knowledges. Fortunately, at thattime, I had opportunity to acquaint with the vast knowledges and experiences with my respected teachers of Dr.
Yoshihisa Hashiguchi, Dr. Katsumi Aoki, and Dr. Takesumi
Yoshimuri et al. However, I was engaged in this project forthree years, and experienced clinically likely; onchocercoma, pretibial depigmentation, and onchocercal dermatitis
etc. on this disease. After this project, I came back to join in
my dermatology clinic. Eventually, my main interest of

study is in the field of photobiology subject. From 1988, I
joined again in a project of cutaneous leishmaniasis, which
was started and still continuing by Dr. Yoshihisa Hashiguchi
since 1986. For which, I already visited once or twice in ayear to Ecuador for past 15 years with Dr. Y. Hashiguchi
and other doctors. We had observed almost a thousand ofpatients with cutaneous and mucocutanenous leishmaniasis
in Ecuador and Pakistan. Our research group carried out theextensive clinical, immunological, histopathological andmolecular biological study of leishmaniasis. As a result, it
could be possible for us to introduce a new diagnostic technique in the detection of parasites species specificity inleishmaniasis, clinical trials with new antileishmanial
agents in the treatment of cutaneous leishmaniasis, and also
invent a novel antileishmanial chemical agent for this disease. We already published our research activities in sevenresearch series reports of studies on new and old worldleishmaniasis, edited by Dr. Hashiguchi. I’m very proud of
it that I had a good opportunity to participate on this report.
Furthermore, I’m very pleased that my young colleagues
are continuing on this subject of tropical medicine. I am optimist and confidant that Dr. Hashiguchi with his colleagues
will have to continue their research works in future. Approximately 30 percents of my all published papers are concerned with the related tropical medicine and parasitological subjects. Finally, I am sincerely grateful to all membersof Japanese Society of Tropical Medicine for their kind cooperation and heartiest support. Fortunately, I am going toretire on end of March, 2006, however I have great desire tocontinue my study, and also to educate our young dermatologists for necessity of investigations related in the fieldof tropical medicine subjects.

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０

JSTM Young Investigator’s Award
THE MECHANISMS OF THROMBOCYTOPENIA IN THE ACUTE PHASE OFSECONDARY DENGUE VIRUS INFECTIONSMARIKO SAITODept of Internal Medicine, Institute of Tropical Medicine, Nagasaki Univ, Nagasaki, Japan

Severe thrombocytopenia and increased vascular permeability are two major characteristics of dengue haemorrhagic fever (DHF). To develop a better understanding of
the roles of platelet-associated IgG (PAIgG) and IgM(PAIgM) in inducing thrombocytopenia and its severity of
disease in patients with secondary dengue virus infection,
the relationship between the PAIgG or PAIgM levels anddisease severity as well as thrombocytopenia was examinedin 78 patients with acute phase secondary infection in a prospective hospital-based study. The decrease in platelet countduring the acute phase recovered significantly during theconvalescent phase. In contrast, the increased levels of
PAIgG or PAIgM that occurred during the acute phase of
these patients decreased significantly during the convalescent phase. An inverse correlation between platelet countand PAIgG or PAIgM levels was found in these patients.
Anti-dengue virus IgG and IgM activity was found in platelet elutes from 10 patients in an acute phase of secondary
infection. Increased levels of PAIgG or PAIgM were significantly higher in DHF than those in dengue fever (DF). An
increased level of PAIgM was associated independently
with the development of DHF, representing a possible pre-dictor of DHF with a high specificity. This data suggest that
PAIgG, PAIgM involving anti-dengue virus activity play apivotal role in the induction of thrombocytopenia and severity of the disease in secondary dengue virus infections. Of
the 46 patients, the plasma thrombopoietin (TPO) levels in
the acute phase were remarkably high, and it was decreasedin the convalescent phase, although still significantly highlevel than those of healthy volunteers (HV). Since there aresome reports that plasma TPO levels depend on the levels of
the megakaryocyte in the bone marrow rather than the levels of peripheral blood platelets, we suggest that the thrombocytopenia in secondary dengue virus infections are also
induced by bone marrow suppression. On the other hand,
the levels of plasma vascular endothelial growth factor(VEGF) in the acute phase were significantly lower thanthose of HV, and they were recovered in the convalescentphase and they didn’t show significant difference between
DF and DHF. This data suggest that the plasma VEGF doesn’t contribute to the increased capillary permeability. (Collaborator: Kazunori Oishi, Institute of Tropical Medicine,
Nagasaki University)

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１

Symposium 1
S1-1) THE DAWNING OF TRAVEL MEDICINE AND IMMIGRANT MEDICINE −INTRODUCTION−TOSHIMASA NISHIYAMA１, ATSUO HAMADA２
１

Dept of Public Health, Kansai Medical University, Osaka, Japan
Japan Overseas Health Administration Center, Japan Labour Health and Welfars Organization, Kanagawa, Japan２

The travel medicine in Japan just started to establishedin academic field. And the area of these fields is not interest
so much in Japanese.
Recently, Japanese overseas travelers are increasingover 1.700 million per year for the advancement of enterprise to the foreign countries and appreciation of Japaneseyen. On the other hand, the foreign workers who work inJapan are increasing as a cheap manpower. These foreigners
sometimes have diseases that are not only general diseases
but also endemic diseases of the mother countries. Howeverthese foreigners sometimes cannot go in an enough medical

treatment because of the difference of the language and culture. In Europe and America, the concept has already been
established as an academic field named immigrant medicine
in the travel medicine. First of all, we would like to discuss
about “What is the location of immigrant medicine in thetravel medicine? Furthermore, we will talk about the actual
medical status for immigrant medicine in Japan, includingin the deal with the foreign workers in the key hospital andclinical office in the region, and the current state of the
medical interpreter who has established recently.

S1-2) MIGRANT MEDICINE IN TRAVEL MEDICINEMIKIO KIMURA
Infect Dis Surveil Ctr, Natl Inst of Infect Dis, Tokyo, Japan

Some people move from one place to another forpleasure, economic benefit, or academic interest, while others move out of necessity or because their old location is nolonger safe. Such human movement is influenced by various factors, including environmental (climate changes,
natural disasters), demographic (increase in the worldwide
population), and socioeconomic ones (globalization of theeconomy, urbanization, easy access to information). These
factors, intertwined in a complex form, have contributed to
an increase in both migrants and travelers worldwide. Migrants often move from a poor country with a &quotoneway ticket&quot, and include immigrants, foreign workers,
asylum seekers, refugees and undocumented immigrants,
while travelers do so from a rich country with a &quottwoway ticket&quot, and include tourists, business travelers,and expatriates. In 2003, the number of individuals living inforeign countries and the number of international arrivals
worldwide are respectively 175 million and 700 million annually, which highlights the enormous volume of human
movement currently occurring. Migrants face language/
communication barriers, insufficient social acceptance, sequelae of tortures and violence experienced before arrival,

and psychological isolation, and are thus prone to psychiatric disorders and drug/alcohol abuse in the receiving countries. Medical personnel seeing migrants need to possess
numerous skills, including the ability to talk and communicate with migrants of different origin, to understand theirpersonal history (including that of migration), to deal withdifferent cultures, and to cooperate with other professionals(nurses, interpreters), not as one individual but as a memberof a network. Medical issues that should be addressed include malnutrition (vitamin deficiencies), infectious diseases (TB, viral hepatitis, malaria), hereditary disorders (hemoglobinopathy), environmental disorders (lead poisoning)and post-traumatic stress disorders. For example, studies
have reported that migrants arriving in Switzerland have ahigher prevalence of TB, HBs-Ag and seropositivity forsyphilis, and those who experience organic violence before
arriving are more likely to have various somatic symptoms.
In addition, countries receiving migrants may have to implement measures to prevent resurgence of some diseases.
In Western countries, attention has been focused on healthissues in VFRs (visiting friends and relatives). Because
VFRs believe themselves to retain immunity to infectious

２２diseases that are prevalent in their home countries, they tend
to neglect necessary precautions. The literature indicatesthat VFRs are more likely to contract malaria, typhoid andhepatitis A while traveling. Although this issue is not as serious in Japan as in Western countries, it appears to be
steadily growing.

S1-3) RECENT TENDENCY OF IMMIGRANT MEDICINE AT HOSPITALS OFSHIGA PREFECTURE AND JAPAN
TAKESHI IDA
The meeting for International Medical Sevices, SHIGA (MIMSS)
Department of Surgery of Kohka Public Hospital[INTRODUCTION and BACKGROUND] According to thestatistics of Shiga prefecture (abbreviated as SP) of 2004,
the registered foreigners in SP are 27,863 [Brazilians
12,856 (46.1%), Koreans (23.2%), Chinese (10.1%), Philippines (7.4%), Peruvians (6.7%) etc, which is about 2.0% of
the whole population of SP]. But, the ratio of foreigners /Japanese in some cities is more than 5%. At the medical
service zone of our hospital, 5361 foreigners are registered(3.8% of about 150,000 inhabitants).
[METHODS] The statistics documents of SP, local governments, Shiga International Association (SIAM) and our hospital, and reports at MIMSS.
[RESULT] Nine cities among local governments of SP,
have consultation windows for foreigners-in Portuguses (9cities), Spanish (1 city), English (4 cities) etc. They can givevarious advice, but cannot attend the medical scene. The
rate of participation of national health insurance by foreigners is estimated to be about 40% in SP. The result of recent
questionnaire about foreign language correspondence todoctors of main 5 departments of 63 hospitals at SP, there
are extremely few doctors who can speak foreign languages
except English. These languages are German (at 4 hospitals), French (1), Spanish (2), Portuguese (1), Chinese (2),Korean (5). We have an average of 1,000 outpatients / dayin our hospital, and about 5-15 foreign outpatients / day.
Operations of foreign patients during recent 8 years, were
207 cases, and the ratio of foreigners to the total cases in
our hospital was about 1.2%. Of 207 cases, orthopedics was
31.2%, and surgery was 30.0%. In addition, there are also
cases of HIV (AIDS), dengue fever,Chagas disease and theother uncommon diseases in SP. Therefore, it is necessary
to take these diseases into consideration even at ordinary
clinic and hospital.
[CONSIDERATION] Many foreigners living in Japan havedifficulty in communication, cruel working conditions,health insurance non-participation etc. According to thestudy of S. Muraki. the number of foreign patients with difficult or impossible communication is estimated to be about
36,000 / day out of all foreigners living in Japan . In order
to settle this a little, we developed a multilingual correspondence PC (joint development with Prof H. Matsuo of Kobe
University , the affiliated hospitals and KDDI) , and got agood result .I also intend to introduce some recent trends
such as medical interpreter authorization system, dispatch
interpreter system and telephone interpreter system , which
are studied by NPO or other groups.

S1-4) PROBLEMS ACCOPANIED WITH ACCEPTING FOREIGN PATIENTSIN SMALL MEDICAL FACILITIES IN JAPANYONEYUKI KOBAYASHI
Kobayashi International Clinic

From Jan.’90 to June ’05, 5982 foreign patients (totally
34902 patients),58nationals were checked at Kobayashi International clinic. Accepting foreigners in medical facilities,
there are some problems. The first is language problem.

English speakings are minority among foreigners in Japan.
correspond to Spanish, Portuguese, Mandarin, Korean, Thaiand so on is urgently. Understanding the culture and thinking way of them is the second problem. To make up confi-

２
３

dence through recognizing each other is only the way to
perform adequate medical treatment. The third is financial
problem. In general, foreigners are very easily sufferingfrom financial problems comparing with Japanese. In addition, a part of the foreigners can’t join or refuse to join
Japanese official medical insrance system. Practicing Informed consent about the charge is important to avoid fi-

nancial trouble. The fourth is difference of the diseases. For
example, tropical diseases are very rare in Japan, so almostof the doctors in the small primary care facilities have seldom experiences not to misdiagnosis. Anyway, how to complete back up system for those 4 problems to help foreigners and doctors in small clinics is important.

S1-5) CURRENT PROBLEMS AND FUTURE SOLUTION IN MEDICALINTERPRETATION/TRANSPLATION IN JAPANTOSHIHIRO MURAJI
AMDA-Hyogo, Hyogo, Japan

In multicultural society, as a product of the rapid
globalization, public service interpretation/translation will
be playing an important role for the foreigners with the divergent cultural backgrounds and language barrier to makea comfortable life in communities where they live. Convention interpretation/translation has been available in Japan,
while the community interpretation recently became necessary in this era of globalization. Community interpretation/translation consists of judicial, medical, and administrative
components. The characteristics of medical interpretation/translation are summarized in 5 folds; 1. advocacy associated, 2. Bidirectional interaction between the interpreter andclient, 3. Information interpreted based on cultural background, 4. Volunteer based activities, 5. Ethical principles
involved. Medical providers and on-going volunteer-based
interpreters have been developing the training courses for
medical interpreters /translators in the last several years.
The curriculum of the course includes medical terminology,
basic concept of each specialties, demonstration of hospital
equipments and ethics to be considered as interpreters inhealth care. The medical interpreting/translation as one ofthe public service should be established for a proper training and licensing in an attempt to create our better society
and to live hands in hands with foreign people.

S1-6) REPORT ON THE PRESENT STATUS OF THE MEDICAL INTERPRETER DISPATCH SYSTEMPILOT PROJECT IN KYOTO, JAPANAIRI TAKASHIMA
Kyoto Center for Multicultural Information and Assistance, Kyoto, Japan

Background: With the increasing number of foreign residents in Japan, concerns regarding health and medical carefor those of limited Japanese language ability have been on
the rise. This has led, in 2003, to the start of this medical interpreter dispatch system pilot project, with the cooperationof government administration, hospitals and a supporting
nonprofit organization. The project dispatches interpretersof Chinese, English and other languages to hospitals whichhave agreed to the terms of the project. Each hospital selects
a coordinator from among the hospital staff and provides
medical liability insurance for the interpreters. Interpreting
charges and transportation expenses are funded by govern-

ment administration. The supporting group screens the applicants, and provides training and on-the-job supervision.
Purpose: Report on the present operational status of the
Project.
Results: The system operated for 234 days in the year 2004,
dealing with 1424 cases in which a total of 1102 people
used the service. The departments where the service wasmost frequently used were neuro-internal medicine (12%),orthopedics (11%) and digestive tract internal medicine(9%). The interpreting services were used in a total of 1703
cases, for the explanation of symptoms and diseases in 1304
cases (76%), medical tests and/or examinations in 186 cases

２４(11%), and medication usage in 74 cases (4%). Before thestart of the project, of the 38 nurses for outpatient surveyed
25 expressed concern about the accuracy of translation, 17
about the increasing number of foreign patients and 7 about
possible problems arising from the interpreters lack ofknowledge regarding patient medical history. At the end of
the pilot project in 2004, of the 23 respondents, 11 ex-

pressed concern about the accuracy of translation, 10 about
the interpreters’ medical knowledge and 4 about patient
confidentiality. While there have been requests for an increase of the number of days and hours, as well as interpreter availability for emergency cases, the problem offunding and financial assistance has yet to be solved.

２
５

Symposium 2S2-1) MEDICAL COOPERATION FROM JAPAN TO AFRICA IN THE 21ST CENTURY; INTRODUCTIONNOBUO OHTA１, HIROSHI ICHIMURA２
１

Dept of Molecular Parasitol, Nagoya City Univ Grad School of Med Sciences, Nagoya, Japan
Dept of Viral Infection & Int Health, Graduate School of Med Science, Kanazawa Univ, Kanazawa, Japan

２

When we think about well-harmonized development of
the world, it is a big concern to realize the situations in the
sub-Saharan African countries. Problems in Africa are intricate in the origin, however, matters of health, especially infectious diseases, are one of the central issues. Through therecent political wind, Japan is requested to share responsibility to solve the problem in Africa. However, difficulties
not only from geographical distance, but also in cultures,
languages and other factors limited available human resources in Japan for cooperation with African countries. It
is, therefore, obvious that we are facing an urgent necessityof development of human resources to be involved in activities in Africa. This symposium is conducted to discuss
about the future strategy of the probable approach from Ja-

pan in the aspect of matters of Tropical Medicine. As the organizers of this symposium, we invited speakers from various areas; persons in political decision-making, in coordination of JICA projects, in NGO activities and in academia.
Each speaker is requested to introduce the current situationand problems in respective project. It is important to havemutual understanding and cooperative scheme to promote
effective international cooperation in Africa, because we realize that each component is not strong enough in Japan.
Through the discussion, the organizers does not expect tohave a tight conclusion about the role of the Japanese scientists in African issue, but we expect that each member ofJSTM share the understanding the problem and start actionneeded for African issues.

S2-2) JAPAN’S CONTRIBUTION IN ACHIEVING THE HEALTH MDGS--- “HEALTH AND DEVELOPMENT INITIATIVE (HDI)”--TARO YAMAMOTO
Deputy Director, Aid Planning Division, Economic Cooperation Bureau, Ministry of Foreign Affairs

The largest number of child preventable deaths is formalaria---- approximately one million deaths per year andthe intervention with the largest single impact on reductionof childhood mortality is the distribution and use of insecticide treated bed nets. Their widespread use will result in:less burden on the health system; less out of pocket expenses; and improved work performance in adult.
The MDG 1 aims at eradication of extreme poverty:
malaria is a disease of poverty, depriving Africa of up to$12 billion every year in lost GDP. Malaria is also clearly
one of the major constraints for achieving the MDG 4 (Reduce Child Mortality) and 5 (Improve Maternal Health).
Due to the high burden of malaria in Africa, where the disease causes about 25% of childhood deaths, malaria in Africa had to be addressed as an urgent priority in order tohave any hope of achieving these goals. Thus, effective prevention of malaria with INTs impacts on almost all of the
MDGs in one form or another. The same can be said forother infectious diseases including HIV/AIDS, tuberculosis
and parasitic diseases. Health is thus the matter of threats toan individual as well as to societies. However, the progress
toward achieving health MDGs (MDG4, 5 and 6: combat
HIV/AIDS, malaria and other diseases) is lagging in many
developing countries. For instance, regarding to MDG 4, wecannot presumably achieve more than a 42% reduction in
the infant mortality rate (the target is two thirds=about 67%
reduction) worldwide at the current pace. As for MDG 5, itis presumed that this goal will not be achieved except in
Middle East and North Africa.
Based on above mentioned recognitions, the government of Japan announced early this year that Japan would
provide 10 million ITNs by the year 2007, targeting children under 5 and pregnant women in Africa, with the expected outcome of 110,000 to 160,000 reduction in childdeath, and recently Japan announced new health initiative,
called “Health and Development Initiative (HDI),” helping

２
６

achieve health MDGs with the financial contribution target
of $5 billion over next five years (FY 2005-2009), in addition to $500 million pledge to Global Fund to fight AIDS,
Tuberculosis and Malaria in the coming years, with the intention of doubling the Official Development Aid toward

Africa in the next three years.
The full text of HDI is available on the web site as below: http://www.mofa.go.jp/policy/health_c/forum0506/hdi.
pdfS2-3) PRESENT SITUATION OF AIDS/HIV INFECTION AND ANTI-RETROVIRAL TREATMENT (ART)IN ZAMBIA: JICA HIV/AIDS AND TB PROJECT IN ZAMBIA
T. MIZUTANI, Y. TAKAHASHI, M. HIROTA, T. KUDOH, K. MURAKAMI AND N. YAMAMOTO
Univ.Teaching Hospital, Zambia Univ
National Institute of Infectious Diseases,JapanFirst case of HIV infection was reported in Zambia in
1984. Thereafter, the government launched to fight AIDS
through formulating National AIDS Prevention and Control
Program followed by construction of The First Medium
Term Plan (1988-1992), The Second Medium Term Plan
(1994-1998) and National Strategic Framework (20012003). Despite these strategic efforts, situation of AIDS/
HIV became worse with time in Zambia. The rate of thepeople living with HIV/AIDS in 2003 is estimated about
16.5% (UNAIDS, Epidemiological Fact Sheets, 2004) andnearly 2 million people are estimated to be infected withHIV among total population (11 million) in Zambia. Since
the rate of dual infection of HIV and TB is very significant,the needs for HIV/AIDS and TB control are very high inthis area. The Zambian government presents HIV/AIDS and
TB control as public health priorities in the National Strategic Plan 2001-2005.

With this in mind, JICA launched the projects in Zambia from 1989. Present project was initiated from 2001
mainly in the University Teaching Hospital of University ofZambia as a major site to implement to improve status of
HIV/AIDS and TB in Zambia. They include; 1) Transfer oflaboratory techniques such as measurement of antibody andantigens, and CD4T cell counting, 2) Monitoring of ART
drug resistance, and 3) Operational research against the patients with TB/HIV dual infection. The project purpose andoverall goal are considered to be relevant and activities are
sufficiently achieved in terms of the needs of Zambian
health sector, Zambian government policy and Japanese
ODA policy.
Status of AIDS/HIV and ART carried out in Zambia
based on 3 by 5 program and our strategies through JICA
project will be presented.

S2-4) THE PROSPECTS FOR THE MALARIA CONTROL, USING BY HOME BASEDAND SCHOOL BASED APPROACH, IN AFRICA
JUN KOBAYASHI
Expert Service Division, Bureau of International Cooperation,
International Medical Center of Japan, Tokyo, Japan

I would like to recommend that the home based management of malaria treatment and school-based malaria
education are a useful additional strategy to strengthen themalaria control program in Africa. The global strategy ofmalaria control in recent years was made on the basis of the
PHC; primary health care management. In the strategy, thestrengthening for public health facilities and village volun-teer in the community are main tools to improve the treatment and the prevention of malaria. However, malaria in
African countries have still been a serious public healthproblem in spite of the efforts to carry out the control programs, which was modified from the global strategy, because of the following factors; hard accessibility to healthfacilities, poverty, lack of confidence in health facilities be-２
７cause of the problem for the quality of health services andlack of uniformity of the service by the community healthvolunteer. In this situation, the home based management formalaria treatment is attracting attention because thestrengthening the treatment to the children by their motheris effective as an early treatment despite uncertainty of diagnosis and treatment. Thus, the private sector such as a pharmacy and a local shop has a share to scale up this strategy.
Malaria control using by the insecticide treated bed net hasremained as a tool of the poverty reduction in Africa, thus,

the behavior change communication to use bed net should
be strengthened. The school based malaria control was
evaluated as a new tool of behavior change communication
to the communities in Southeast Asian countries. This new
strategy promotes the schoolchildren as a health messenger
to the community using by Participatory Learning Action in
the education. Regardless of the low rate of the pupils in thecommunity in the Africa, the school-based approach might
be effective as a behavior change communication.

S2-5) THE ROLE OF COMMUNITY HEALTH WORKER IN INFECTIOUS DISEASE PREVENTION
IN SENEGALCHIKAKO SHIINA１, NDEYE AMY BATHILY２, ABOUBACRY FALL２, MAYUMI SHIMIZU１, REIKO HAYASHI３
１

JICA Project for the development of human resources in health, Dakar, Senegal
２
Ministry of Health and Medical Prevention, Dakar, Senegal
３
Linz Co.Ltd, Tokyo, Japan[Introduction] The purpose of the JICA Project for the Development of Human Resources in Health, Republic ofSenegal, is to strengthen the system for educating healthpersonnel working in primary health care facilities. The
project is being implemented in three sectors from November 2001 to October 2006. Activities in the sector concerning training of community sanitary agents (ASC: Agents
Sanitaire Communitaires) are aimed at establishing an appropriate training system in the test area (Fatick Region,
Sanitary District of Gossas). [Outline] In Senegal, the end
institutions of primary health care are the health huts where
the ASC educate residents, treat wounds and handle basic
drugs. The present situation is such that the ASC working in
the health huts focus mainly on treating wounds and administering basic drugs and little emphasis is given to educating
residents. [Method]ASC training for 32 trainees from 32
villages in Gossas district was held at 9 health posts for 3

months. The trainees were instructed in the necessity andmethods of educating residents by the health post chiefs(state nurses), using the ASC training manual. After the
training, the health post chiefs regularly visited the ASC
and health huts to provide guidance. To promote control of
infectious diseases, ASC education activities included
teaching residents about insecticide-treated mosquito nets toprevent malaria, educating them about HIV/AIDS, promoting vaccinations and administering medicines against
worms. [Results] As of July 2005, all 32 ASC were engaged
in health work one year after the training. Of the 32, 17
regularly undertake education of residents. By the end of
May 2005, all 640 insecticide-treated mosquito nets distributed to the health huts in the 32 villages had been sold toresidents. [Consideration]Together with the commitment of
the health administration, ASC are essential to infectious
disease prevention among residents.

S2-6) PREVAILING ESSENTIAL MEDICINES IN AFRICAKAZUKO KIMURA
Drug Management and Policy, Graduate School of Natural Science and Technology,
Kanazawa University, Kanazawa, Japan

Access to essential medicines has improved considerably during the past quarter century, but is still inadequate

for one-third of the world’s population. Not only antiretroviral drugs, but even ordinary medicines, such as２
８remedies against respiratory infections and diarrhea, are unavailable to many of these people. According to the WHO,
only 50-80% (’99) of people in Cote d’Ivoire, one of themost prosperous countries in Africa, have regular access toessential medicines and the situation is much worse in many
south Saharan countries. The reasons include immature infrastructure and weak regulatory control. Every stage fromdevelopment to manufacture, distribution and use of medicines is well controlled in developed countries, as it has
been learned that low-quality medicines directly threaten
human life. However, only a third of Medicine Regulatory
Authorities (MRAs) in the world are functioning properly,
while another one third are not fully adequate, and the rest
are ineffective or absent. We show here that inadequate control leads to loss of public confidence in pharmaceuticals.
By means of authenticity investigation in collaboration with
MRAs and manufacturers, we investigated the authenticityof 353 pharmaceutical samples, consisting of anthelmintics,
antibiotics and antipyretics, collected in July 2004 in Coted’Ivoire. Medicines were sold not only by licensed pharmacies, but also by unlicensed street shops and street vendors.
The latter sold medicines at one-fifth lower prices than thepharmacies. Out of 353 samples, only 75 (21%) had
authorization from the DMP (MRA of the Cote d’Ivoire)and 278 (79%) did not. All medicines sold at pharmacies
had authorization, while 95% of medicines from street
sources did not. Two authorized medicines (3% of 75) wereidentified as counterfeit, while 49 unauthorized medicines(18% of 279) were counterfeit. Without in-depth investigation, it is impossible in most cases to distinguish counterfeit
medicines from authentic ones. Robust regulatory control of
medicines, such as licensing of pharmaceutical selling andauthorization of medicines, is indispensable to ensure trustworthy medicines for medical professionals and patients.
Furthermore, dispensing of prescription medicines, such as
antibiotics, without prescription may well lead to the development of resistance. It is important to promote rational useof medicines. Considering the scale of the problem, it isnecessary for countries to develop a comprehensive masterplan covering access, quality and rational use of medicines
for the pharmaceutical sector and for pharmaceutical management, and to implement it vigorously. We appreciate cooperation of concerned MRAs, manufacturers, PSI and
WHO.

２
９

Symposium 3S3-1) THE ROLE OF LABORATORY IN INTERNATIONAL COOPERATION IN THE FIELD OF
TUBERCULOSIS AND HIV CONTROLKATSUNORI OSUGAThe Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan

A third of the 40 million people currently living with
HIV in the world are also infected with TB bacilli. The coinfection rate is much higher in the sub-Saharan Africa.
Once those already infected with TB bacilli also become infected with HIV, they are approximately 10 times more
likely to develop TB disease than those without HIV infection. Since 60% of the people infected with HIV globally
live in the sub-Saharan African countries, the TB cases inthis region are on the increase. Many of them die of TB. In
2003, the incidence rate of TB in the world decreased except in the WHO African Region. On the other hand, whilea third of the world population is estimated infected with
TB bacilli, most of them are living in populated Asian countries. HIV infection is rapidly spreading in Asia in recent
years. Not only limited in sub-Saharan Africa, TB/HIV coinfection is becoming a major concern in Asia as well. To
control TB, the WHO introduced a new strategy called
DOTS in early 1990s. As of 2003, DOTS reached 77% of
the entire population in the world. More than 80% of thosediagnosed with TB have been successfully treated. For HIV/AIDS control, the introduction of the ARV in developing

countries has revolutionized the HIV strategy. With the 3 by
5 initiative of the UNAIDS/WHO, the ART (treatment with
ARV) has become possible. Financial support to carry out
effective TB and HIV control in the developing world has
also been made available. Following the Infectious Disease
Initiative declared during the Okinawa summit in 2000, theGlobal Fund to Fight AIDS, malaria, and TB was established in 2002. Once the infectious disease control with theadequate treatment and the financial support is made possible, the capability of a laboratory becomes crucial. For instance, the CD4 count is necessary to determine when to
start ART. Monitoring of the drug sensitivity also becomes
important. The well functional laboratory is needed to properly diagnose various opportunistic diseases. For the TB
control, in addition to the sputum smear examination and its
quality control, the drug sensitivity test and other advanced
technological development is also needed. How to integrate
the public health strategy for infectious disease control withthe adequate laboratory technology has become crucial ininternational cooperation for TB and HIV control.

S3-2) TB/HIV FIELD RESEARCH ACTIVITIES IN CHIANG RAI, THAILANDNORIO YAMADA, HIDEKI YANAIThe Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan

Chiang Rai Province, Thailand, is the area which had
seen a HIV epidemic in the 1990s. Due to the HIV epidemic, tuberculosis incidence had increase since early
1990s. To deal with tuberculosis, Research Institute of Tuberculosis (RIT), Japan Anti-tuberculosis Association,
started TB/HIV Research Project in collaboration with Thai
Ministry of Public Heath and other organizations. In thispresentation, we report the project activities focusing on therole of laboratory. One of main objectives of the Project isepidemiologic researches of TB in HIV prevalence areas.
As a core project activity, a population-based surveillanceof tuberculosis was set up and provincial TB registry data

since 1987 including treatment outcome was computerized.
HIV voluntary counseling/testing and drug sensitivity testing were instituted and have been an integral part of the surveillance system since 1996. Because proportion of smear
negative tuberculosis and proportion of MOTT in HIV infected population is higher than in HIV uninfected population, culture examination is important in HIV high prevalence areas. To monitor the trend of drug resistance TB, theproject has established TB laboratory system through collaboration with the national tuberculosis reference laboratory of Thailand. Solid media based culture laboratory forprimary culture is carried out at the provincial hospital and３０isolates are transferred to the national reference laboratory
for identification and drug susceptibility examinations. Recently liquid media culture system has been introduced forfurther improvement of TB laboratory through collaboration
among US-CDC, Thai MOPH and the project. Using theisolates, to assess the transmission dynamics of TB in the
HIV high prevalence area, RFLP examination has been carried out in collaboration with Mahidol University. Other objectives of the project include researches related to healthservice of reducing TB incidence and mortality of HIV coinfected TB. CD4 measurement is carried out with a flowcytometer donated to a community hospital by Japanese

Government. Examination of blood concentration level ofanti-retroviral medicines and viral load, which is required
for studies of anti-retroviral medicines for HIV co-infected
TB patients, is carried out in the facility of Thai Red Cross
HIV research. For virologic studies of HIV, collaboration
with Thai NIH, Bangkok and Medical Science Centre in theprovince has been established. The laboratory system is required for not only biomedical but also epidemiologic studies of TB/HIV as mentioned above. It is though importantto establish collaboration with local organizations having
laboratory in middle-income countries like Thailand.

S3-3) A MOLECULAR ANALYSIS OF TUBERCULOSIS INFECTION IN ZAMBIAN PRISONSSATOSHI MITARAI
Bacteriology Division, the Research Institute of Tuberculosis,
Japan Anti-Tuberculosis Association

A molecular analysis of tuberculosis infections has
been conducted in Zambian prisons. The consecutive 3 sputum samples were collected from the inmates of 14 prisonswith respiratory symptoms through June 2000 to January
2001. A total of 1,050 inmates were enrolled into the study
and 3,130 specimens were collected. The male proportion
was 98% and mean age was 30.2±8.1. A total of 259 M.
tuberculosis strains were isolated and 101 strains were analysed using standard restriction fragment length polymorphisms (RFLP) and resistance ratio drug susceptibility testing method, subsequently. The strains conformed 18 clusters and the size varied from 2 to 22. The major 2 clusters
were considered as most prevalent M. tuberculosis strains inZambia. In each prison, several inmates in a same cell had
pulmonary tuberculosis and the M. tuberculosis isolates

showed same RFLP pattern. Majority of the clusters towhich the inmates belonged were cluster 1 or 2. They might
be a reflection of general prevalence of tuberculosis in thecommunity and the patients seemed to be infected outside
the prison. However, two inmates in Maximum Kabwe
prison had tuberculosis that pathogens classified into rarecluster, and it seemed to be an intra-cell infection during thecustody. In general, the conditions in prisons in developing
countries are terrible and a few countermeasures are taken
to prevent the dissemination of any infectious diseases. The
high prevalence of tuberculosis in prisons is mainly due tooutside infection, but a part of them could be infected anddeveloped in the prison. Any countermeasure must be taken
to prevent an outbreak of tuberculosis in prison and to diagnose the patient in an immediate manner.

S3-4) HIV SEROPREVALENCE SURVEY AMONG TB PATIENTS IN CAMBODIA (2003 AND 2005)
NAMIKO YOSHIHARAThe Research Institute of Tuberclosis Japan

Not received

３１S3-5) WHERE ARE GOING LABORATORY PROJECTS IN DEVELOPING COUNTRIES?
−THE CASE OF HIV/AIDS & TB CONTROL PROJECT IN ZAMBIA−
NAOMI WAKASUGIInternational Medical Center of Japan, Tokyo, JapanIn Europe “Hospital” came into existence in 17th century, and in 19th century the pathogens of infectious diseases have been discovered by Pasteur, Koch and other scientists in succession.
At the same time Tropical Medicine has been developed, which was the root of international cooperation withlaboratories in developing countries nowadays. Calmette
produced a laboratory in Saigon in Vietnam in 1891 as thefirst Pasteur institute overseas, and then Yersin went toHong-Kong and worked for Pest research in a laboratory
like a shanty in 1894. Since then Pasteur institute has continued the existence of about 30 laboratories in developing
countries for more than 100 years.
Looking at international medical cooperation from Japan, we have a certain history of laboratory project in developing countries. Particularly it should be noted that themain technical assistance to African countries has been implemented into laboratories such as Noguchi institute in
Ghana, KEMRI institute in Kenya and UTH laboratory in
Zambia by producing new laboratory or strengthening existing laboratory, developing research and building human capacity. These laboratories lasted for more than 10 years, andwhether and how these should be continued is being dis-cussed now. The decision should be done very carefully
when the role of laboratories has become important more
and more in Africa facing a serious threat of AIDS and TB
and the start of global initiative for care and treatment.
In Zambia JICA started a technical cooperation with
University Teaching Hospital (UTH) by establishing virallaboratory in 1989 and served as a base for the surveillanceof and research for infectious diseases. On the other hand its
research-oriented way of cooperation has been criticized.
However the third-phase project since 2001 named HIV &TB control project in Zambia has focused on two main objectives: 1. To strengthen and sustain UTH laboratory andcountrywide laboratory system. 2. To utilize effectively thecapacity of the laboratory to national HIV & TB control.
The activities with particular mention are: 1. Countrywide
expansion of less expensive CD4 count method. 2. External
quality assurance of sputum smear testing for TB. 3. Operational research for community-based ARV therapy to HIV/
TB coinfected people using DOTS.
The comments will be presented on how should be thefuture of laboratory project in Africa, what is the barrier tothe continuity, how should we address laboratory projectwith what understanding of its role and importance.

３２

Symposium 4S4-1) WHAT ARE VECTORS? HOW SHOULD WE CONTROL THEM?
MASAHIRO TAKAGI１, MASAAKI SHIMADA２
１

Department of Vector Ecology & Control, Institute of Tropical Medicine (ITM), Nagasaki University
２
Research Center for Tropical Infectious Diseases, ITM, Nagasaki University

Vector-borne diseases are still one of major issues intropical medicine. Their transmission dynamics looks only
slightly different from other common infectious diseases, ofwhich transmission cycles consist of two organisms, hostand agent (pathogen). However an additional third organism,
such as mosquito, tick, snail, and so on as vectors makes
more complicate the transmission dynamics of the vectorborne diseases. Analysis in mutual interaction among theseorganisms and the functional response of each organism
against environment need a flexible approach beyond thehost-parasite relationship. Therefore scope to vector-borne
diseases should be deepened only when we spire our inter-est to not only medical science but also to biology, especially to ecological achievements based on interdisciplinary
approach. This symposium hopefully provides recent scientific information on the mode of change in epidemics ofmalaria, dengue fever, schistosomiasis, and tick-borne diseases, all of which might be caused by the adaptive changes
in local vector or intermediate host populations reacting tonatural and socio-economic environmental changes. Yielding environmental friendly vector/intermediate host control
strategy is the key concerns toward the control of vectorborne infectious diseases.

S4-2) LIFE HISTORY ADAPTATION AND TRANSMISSION OF HUMAN DISEASES IN MOSQUITOESYOSHIO TSUDA
Department of Medical Entomology, National Institute of Infectious Diseases, Tokyo, Japan

Aedes aegypti is the most important vector of dengue
fever in Southeast Asian countries. This species has originated in central Africa and two subspecies are distinguished.
One is a sylvan form, Ae. aegypti formosus, found in forest
and the other one is a domestic form, Ae. aegypti aegypti,
found in domestic habitat. It is proposed that dengue virus
may have originated in a forest cycle in Southeast Asia. The
domestic form Ae. aegypti aegypti has a good ability toadapt to domestic environments and established a close relationship with human throughout tropics. Therefore, thisspecies becomes an efficient vector of human diseases, suchas dengue fever, yellow fever, filariasis etc, in tropical countries. Since no vaccine is available now for dengue fever,the basic strategy of dengue control based on the vector
control, especially the source reduction. To effectively reduce larval population it is necessary to know key containers of the target area through a house survey. From January
to February 2005 a big outbreak of dengue hemorrhagic fe-

ver occurred in Dili, East Timor. Results of vector situation
survey showed that plastic bottles of 5-liter volume, drums
and used tires were the main breeding sites of Ae. aegypti inDili, and control measures focused on these breeding sites
were recommended as the first stage of the vector control.
The vector situation surveys conducted in Southeast Asian
countries showed that kind and the composition of containers used for larval breeding of Ae. aegypti differ greatly
among localities because of the difference in climate, economic conditions, and life style. There is a significant
change in the composition and relative importance of containers after an effective control of breeding sites. Some
containers less important for larval breeding before are preferred for oviposition and the relative importance of thesecontainers for larval breeding becomes higher. This breeding site shift might be the result of adaptive changes in life
history of Ae. aegypti.

３３S4-3) AFRICAN MALARIA VECTORS AND THEIR RECENT STUDIESNOBORU MINAKAWA
Faculty of Medicine, Saga University, Saga, JapanThe major malaria vectors in Africa are Anopheles
gambiae, A. arabiensis and A. funestus. Anopheles gambiaeand A. funestus are relatively more anthropophagic and endophilic than A. arabiensis. Larvae of A. gambiae and A.
arabiensis frequently occur in small, temporary and open
habitats. The egg to adult duration of A. gambiae and A.
arabiensis is usually 7-10 days under the optimal condition.
Breeding sites of A. funestus are limited to large water bodies with aquatic vegetation, and they require a few weeks tomature. Anopheles gambiae and A. arabiensis are difficult
to separate morphologically for both adults and larvae,
therefore, they were treated as A. gambiae s.l. in past studies. Since the mid 90’s, these two species have been identified using the rDNA-polymerase chain reaction (PCR)
method. A recent biogeographical study using the PCR
method reported that A. arabiensis was not found in thehighland area above 1400 m elevation in western Kenya,
and A. gambiae was not recorded in the Great Rift Valley.
The result suggests that A. arabiensis is more adapted todry climate than A. gambiae. Studies in population genetics
also found that populations of these three species are genetically separated by the Grate Rift Valley. Since the late 80’s,
malaria epidemics have occurred in multiple sites in East
African highlands (above 1500 m). Several hypotheses havebeen proposed to explain the increased malaria transmission
in the highlands, including land-use changes and global climate changes. Recent studies suggest that global warming
is not directly related to highland malaria. Although malaria
parasites influence lifespan and fecundity of mosquitoes,
the studies have conflicting results, and more research isneeded in the interactions between mosquitoes and parasites.
To reduce malaria incidence, insecticide-treated bed nets are
effective. However, the nets have to be used continuously ina large area. For larvicides, the environmental safe toxin
from Bacillus thuringiensis var. israelensis and B. sphaericus has been considered. Studies in genetically modified
mosquitoes (GMM) have been also active, but applicationof GMM is still far from reality.

S4-4) INTERMEDIATE HOST SNAIL OF SCHISTOSOMIASISSHINICHI NODA
Research Center for the Pacific Islands, Kagoshima Univ, Kagoshima, JapanThe application of chemical compounds, toxic to theintermediate host snail, was the main measure of control for
schistosomiasis before using prazuquantel . Whenpraziquantel was introduced, it became the drug of choicein the great majority of endemic countries. However, the information for the intermediate host snail is still essential forthe control of schistosomiasis. I show some facts for intermediate host snail with an expectation in the increase of interest in snails. Snail population number and transmission
cycle: Fluctuations in snail populations, the rate of infection
and the production of cercariae are generally strongly influenced by the climate. The information on snail populations
and transmission cycles is indispensable for the selection oftreatment times. Competition between snail species: Members of Ampullariidae and Thiaridae have been successfully
tried as competitors of Biomphalaria spp. in many of theWest Indian islands. Various species of aquatic snails are effective as decoys or sponges to intercept schistosoma miracidia. Environmental management: We attempted to control
snail population in Mwachinga and Mtsangatamu villages
in Kenya. In Mwachinga village, the river dries up in thedry season, with the subsequent formation of small pools.
Towards the end of the dry season, these pools dry up completely. However, snails can survive under the vegetation
which maintains an appropriate humidity. Snails in thepools were eliminated by scooping, and the river bed was
dried by clearing the vegetation. In Mtsangatamu village,
the modification of river streams was carried out in the partof river of which the flow is perennial. The snail habitats
were reduced by the clearing of water plants and concentrating the stream water into a narrow channel.

３４S4-5) VECTOR ECOLOGY AND PREVENTIVE STRATEGY FOR TICK-BORNE
EMERGING/REEMERGING DISEASES IN ASIANOBUHIRO TAKADA
Dept of Pathological Sciences, Faculty of Medical Sciences, Univ of
Fukui, Fukui, Japan

Outbreaks of tick-borne emerging/reemerging infectious diseases are depend on vector competence of tickfauna in each one of endemic areas. But vector survey andpreventive strategy are not easy to complete in each area,
because of complicated factors; double vector species, genetic polymorphology of pathogens, tick habitats associatedwith geology and climate, irregular prevalences of pathogens among reserviors and latent infection among local inhabitants. Herein, vector competences of spotted fever,
Lyme disease and babesiosis are presented from geopathological and genetic epidemiological viewpoints on a relationship between the Japan Islands and Asiatic Continent.
Based on our surveys, new information as follows; southern

limit of northern species Ixodes persulcatus, wide distribution of Asian species Ixodes ovatus and southern species
Ixodes granulatus, unexpected diversity of spotted fevergroup common to Japan and Asiatic Continent, migratory
birds-borne Lyme borreliae in Far East, diversity of rodentborne babesiae in Japan and southern China. Thus, tick vector ecology is comfused arround Asia including Japan. To
make a plan for preventive strategy to tick-borne infectious
diseases, I propose to integrate various information on tick
vectors in Asia, such as a map of ticks and diseases withreference to geological information system (GIS) with computerizing, and colaboration with any medical support projects to Asian countries.

３
５Workshop C-1
14C-01) THE SPLENOMEGALY OF NC/NGA MICE INFECTED WITH PLASMODIUM BERGHEIYOSABURO OIKAWA, TERUAKI IKEDA
Dept of Medical Zoology, Kanazawa Medical University, Ishikawa, Japan

About for the splenomegaly which happens in case ofmalaria infection, it compared and examined ddy mice andNC/Nga mice. Plasmodium berghei which were imparted
from Teikyo University and it is subcultured in our laboratory for more than 20 years were used in all experiment.
When inoculating the blood of the infected mice intraperitoneally to ddy mice, the splenomegaly becomes remarkableat the 4th day of infection and reaches in the maximum at
the first week of infection but the majority of mice died at
this point. When administering Fansidar to the mice at the
4th day of infection, the malaria parasite in the blood disappeared but the splenomegaly of the treatment mice at thefirst week of infection were approximately as equal to thoseof the untreated mice at the first week of infection (It compares at the spleen/body weight ratio). In the meantime,
when the similar examination was done using the NC mice,the spleen/body weight ratios of normal NC mice were significantly smaller than those of normal ddy mice, and thosewere increased at the first week of malaria infection even toalmost equivalent with the spleens of normal ddy mice. The
majority of malaria infected NC mice also died in the firstweek of infection. When the mice were treated by Fansidar
at the fourth day of infection, the malaria parasite in the
blood disappeared and the spleen/body weight ratio almost
equivalently increased with the enlarged spleens of ddy
mice of the first week of infection.
It is known generally that the degree of thesplenomegaly in malaria infection differs by the strain of
mice, and the relationships between the defence mechanisms were reported. In present experiment, because thesplenomegalies in the infected mice were slighter even in
NC mice than ddy mice, the possibility in which some disadvantages occurred to the organism was considered. However the clear difference could not be found in the change ofthe parasitism in malaria infection and the death time inboth mice. In future we want to examine the reason why the
splenomegaly of NC mice almost equivalently increases
with the ddy mice after the malaria treatment.
These results were recognized in fortuity in the experiments of malaria infection which were given as the problems to the students of the selection class throughout several years, and we want to thank them.

14C-02) GENE CONVERSION AND EXTENSIVE POLYMORPHISM
OF THE RHOPH1/CLAG FAMILY MEMBERS IN PLASMODIUM FALCIPARUM
HIDEYUKI IRIKO１,２, OSAMU KANEKO１, HITOSHI OTSUKI１, TAKAFUMI TSUBOI２, MOTOMI TORII１
１

Dept of Mol Parasitol, Ehime Univ Sch of Med, Ehime, Japan
Cell Free Science and Technology Research Center, Ehime Univ, Japan

２

The Plasmodium falciparum high molecular mass
rhoptry protein (Pf RhopH) complex is important for parasite growth and comprises three distinct gene products:
RhopH1, RhopH2 and RhopH3. P. falciparum RhopH1 isencoded by members of the previously- termed clag
(cytoadherence-linked asexual gene) multigene family that
we have now renamed as rhoph1/clag. Because the polymorphism of the pathogen protein contributes an evasion
from host immunity, we determined the nucleotide sequences corresponding to the open reading frame for fiverhoph1/clag members, rhoph2, and rhoph3 in 4 culture-adapted lines (approximately 113 kb total). Sequences werecompared with those from the 3D7 parasite line in the
genomic database. We found that among seven genes, clag9,
rhoph2 and rhoph3 were relatively less diverse, similar tothe other known rhoptry proteins, such as rap-1. However
four rhoph1/clag members were highly polymorphic comparable to the micronemal proteins when full length sequences were compared. Interestingly, all of four clags
show the highest diversity at amino acid 1000-1200 and thedegree is comparable to the diversity observed in the molecules exposed on the merozoite surface, such as merozoite

３
６

surface proteins-1 and -2. Additional sequences of thepolymorphic region in four clags in more than 20 parasite
lines illustrates the extensive diversity of this region, whichwere never observed in the molecules located in the apicalorganelle of merozoites. The gene conversion event was detected between the most diversified clag3.1 and clag3.2,
which might serve as a driving force to accumulate poly-morphism. Furthermore in several culture-adapted parasite
lines, regions between clag3.1 and clag3.2 were not detected from gDNA probably due to a recombination event
between the two closely related clag3 genes. The highly
polymorphic nature of the RhopH1 suggests that the RhopH
complex is under selective pressure and RhopH1 is the target domain.

14C-03) STRUCTURE AND EXPRESSION ANALYSIS OF A MULTIGENE FAMILY
OF GP82 OF TRYPANOSOMA CRUZISONGTHAMWAT DUJDOW１, KAZUO KAJIHARA１, MIHOKO KIKUCHI１, TETSUO YANAGI２, HIROO HIGO３, KENJI HIRAYAMA１
１

Dept. of Molecular Immunogenetics, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan
２
Dept. of Protozoology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan
３
Dept. of Parasitology, Kyusyu University, Fukuoka, Japan

The infective forms of Trypanosoma cruzi, the causative agent of Chagas disease, are metacyclic trypomastigote
form in excreta of triatomine vectors and trypomastigote in
the blood stream of mammalian host. Metacyclic trypomastigotes express stage specific glycoprotein 82kDa (gp 82).
The gp 82 is involved in the invasion of parasites into thehost cells by inducing Ca２＋ signal in target cells by the attachment with cadherine. The functional gp 82 is suggested
to be member of a multigene family related to the transsialidase family. To investigate the role of gp82 in pathogenesis, we studied gene structure and expression of gp82
in the human isolates, Peru 1 and Peru 2 strain derived from
Peru, We amplified the gp82 gene using specific primers,
cloned into E. coli. Then restriction fragment length polymorphism (RFLP) of 25 clones of the gp82 full length of
PCR fragments from genomic DNA of each strains wasanalyzed after EcoR I and Hind III digestion. The result
showed that A, B, C, and E different restriction fragments
patterns were found in Peru 1 and Peru 2 strains. We further

estimated the copy number of the A, B, C and E types genes
in the PCR products by using cloning and PCR specificprimer for each type. A, B, C and E types were found 4%,13%, 8% and 61% clones in Peru1and 1%, 12%, 15% and
43% clones in Peru 2 respectively. Another type (similar E)
of gp82 (13 from Peru 1, 24 from Peru 2) was also detectedby this analysis. The full length DNA sequencing analysis
revealed that inter-types homology was 95〜98%. and theintra-types homology was 85%. We studied expression levelof detection types of the gp82 gene in epimastigote andmetacyclic trypomastigote stages by using real time PCR.
We compared the expression levels of the different stages ofT. cruzi, normally epimastigote and metacyclic each types
of gp82 gene by using actin gene expression as control
Within the multiple genes belonging to the same gp82
family, type C gene was some how specifically activated at
the metacyclic stage and the expression levels of the gp82
genes were suggested to be independent from the copy
number in the genome.

３
７

14C-04) CRYSTAL STRUCTURE AND CATALYTIC MECHANISM OF TRYPANOSOMA CRUZIDIHYDROOROTATE DEHYDROGENASEDANIEL K. INAOKA１, HIRONARI SHIMIZU１, TOMOO SHIBA２, ARIHIRO OSANAI１, EIZO TAKASHIMA１,
TAKESHI NARA３, TAKASHI AOKI３, GENJI KURISU２, SHIGEHARU HARADA４, KIYOSHI KITA１
１

Department of Biomedical Chemistry, The University of Tokyo, Japan２
Department of Life Science, The University of Tokyo, Japan３
Department of Parasitology, Juntendo University, Japan
４
Department of Applied Biology, Kyoto Institute of Technology

Chagas disease (American trypanosomiasis) is causedby the flagellate protozoan parasite Trypanosoma cruzi (T .
cruzi) and affects approximately１６to１８million people inCentral and South America. A large percentage of Chagas
patients receive no specific anti-parasitic therapy because of
the ineffectiveness and toxicity of existing pharmacologic
agents. Hence better therapeutic agents are urgently needed.
Dihydroorotate dehydrogenases (DHODs) are flavoenzymes catalyzing the oxidation of L-dihydroorotate (DHO)
to orotate, the fourth step and the only redox reaction in thede novo pyrimidine biosynthesis pathway. T . cruzi DHOD
(TcDHOD) is a cytoplasmic enzyme and utilize fumarate asphysiological oxidant suggesting that it is involved not onlyin the de novo biosynthesis of pyrimidine but also in redox
homeostasis of the parasite. In contrast, human DHOD is

attached to inner mitochondrial membrane and utilize respiratory quinones as physiological oxidant. This great diversity between parasite and host DHODs makes this enzyme apotential target for new chemotherapeutic drugs. Determination of the structure of TcDHOD should help in the development of new TcDHOD-specific drugs. This should
also help to clarify the catalytic mechanism of dihydroorotate oxidation by family 1A DHODs. Here I report the Xray structure analyses of native TcDHOD and the enzyme
complexed with substrate and products such as DHO, orotate, fumarate, succinate and an inhibitor oxonate. These
structural data confirmed at atomic level the ping-pong Bi
Bi mechanism proposed for TcDHOD and it will definitively help to understand the proton and electron transfer
steps of the DHODs in much greater detail.

14C-05) MUTATIONAL ANALYSIS OF TRYPANOSOME ALTERNATIVE OXIDASE (TAO) AS A POTENTIALTARGET FOR TRYPANOSOMIASIS CHEMOTHERAPYKOSUKE NAKAMURA１, KIMITOSHI SAKAMOTO１, YASUTOSHI KIDO１, TAKASHI SUZUKI２, MITSUKO SUZUKI２,YOSHISADA YABU２, NOBUO OHTA２, AKIKO TSUDA３, MISAO ONUMA３, KIYOSHI KITA１
１

Dept of Biomed Chem, Univ of Tokyo, Tokyo, Japan
Department of Molecular Parasitology, Nagoya City University, Graduate School of Medical Sciences
３
Graduate School of Veterinary Medicine, Hokkaido University

２

African trypanosomiasis, or more commonly known as
sleeping sickness in humans and nagana in cattle, is caused
by a trypanosome parasite infection, and is transmitted bytsetse fly. Trypanosome alternative oxidase (TAO) of African trypanosomes is an ideal target for medicinal chemotherapy, since it dose not exist in host mammals. We havepreviously shown that antibiotic ascofuranone, which is isolated from phytopathogenic fungus, Ascochyta visiae, wasfound to specifically target this enzyme, indicating that thesite of inhibition is the same or close to its quinol substratebinding pocket. In this study, we have identified residues
that are involved in the active site of the recombinant Try-panosoma vivax alternative oxidase by alanine-scanningmutagenesis. Using multiple sequence alignment of mitochondrial alternative oxidase (AOX) including TAO andplastid alternative oxidase (PTOX), we have identified astrong conservation of a glutamate and a tyrosine residue
with 6 amino acids apart and an existence of the important
motif of -E(X)６Y- . The alanine scanning mutagenesis ofglutamates and tyrosines has revealed that the essentiality of
those residues is highly specific. We have concluded thatthe -E(X)６Y- motif consititutes in the active site of the enzyme, as similarly in the group of other membrane-bounddiiron carboxylate proteins, which are previously reported.

３
８

Our results have indicated a more detailed picture of the active site of TAO. More detailed analyses are underway toidentify the enzyme’s active site, which can potentially become the site to be inhibited by a drug.

14C-06) ROLES OF CD8＋ T CELLS FOR ACHIEVING THE CONTROLOF TRYPANOSOMA CRUZI INFECTION
YASUSHI MIYAHIRA１,２, YASUHIRO TAKASHIMA３, YASUNOBU MATSUMOTO３, SEIKI KOBAYASHI４,TSUTOMU TAKEUCHI４, KO OKUMURA２, HIDEOKI OGAWA２
１

Dept. of Parasitology, Juntendo Univ. Sch. Med., Tokyo, Japan
２
Atopy Research Center, Juntendo Univ., Tokyo, Japan
３
Lab. Global Anim. Resource Sci., Grad. Sch. of Agri. Life Sci., Univ. of Tokyo, Tokyo, Japan
４
Dept. of Tropical Medicine and Parasitology, Keio Univ. Sch. Med., Tokyo, Japan

Trypanosoma cruzi (T. cruzi) is the etiological agent of
Chagas’ disease in Central and South America. We previously identified a major epitope of trans-sialidase surface
antigen (TSSA) recognized by CD8＋ T cells in T. cruziinfected C57BL/6 mice and have demonstrated that vaccination with plasmid DNA encoding TSSA can induce
CD8＋ T cell-mediated protective immunity against lethal T.
cruzi infection. Vaccination using recombinant viral vectors
has become a promising strategy to induce T cell immunity
against intracellular infectious agents. Adenovirus and vaccinia virus have been shown to be the most efficient vectors
for inducing protective immune responses against several
infectious diseases. In the present study, we demonstrated

that vaccination with recombinant adenoviral and vaccinia
viral vectors expressing a single CD8＋ T cell epitope,
ANYNFTLV, which is derived from a T. cruzi TSSA antigen, was effective for protecting mice from lethal T. cruzi
infection. We also found that recombinant vaccinia virus expressing receptor activator of NFκB (RANK) ligand exhibited an adjuvant effect for enhancing the induction of
ANYNFTLV-specific CD8＋ T cells. These findings demonstrate that the immune response directed against a single
CD8＋ T cell epitope is sufficient for controlling the lethal T.
cruzi infection, providing a new basis for improving vaccine strategies against Chagas’ disease.

14C-07) DEVELOPMENT OF TWO-STEP DNA VACCINES TARGETING THE LIVER-STAGE
MALARIA PARASITES BASED ON THE UBIQUITIN-PROTEASOME SYSTEMKUNISUKE HIMENO１, J IANYING SHEN１, XUEFENG DUAN１, HAJIME HISAEDA１, KEIJI TANAKA２
１

Department of Microbiology and Immunology, Graduate School of Medical Sciences, Kyushu University, Japan
２
Tokyo Metropolitan Institute of Medical Science

CD8＋ T cells have been implicated as critical effector
cells in protection against preerythrocytic stage malaria. We
have reported that DNA vaccines encoding an ubiquitinfused antigen preferentially induce the main effector CD8＋
T cells through efficient protealysis mediated by theubiquitin-proteasome pathway. In this study we constructed
plasmids encoding ubiquitin-fused circumsporozoite surface protein (CSP) and ubiquitin-fused merozoite surface
protein 1 (MSP1), respectively, and co-immunized the micewith these two plasmids , then challenged with sporozoitesof lethal plasmodium yoelii strain. These two-step DNA
vaccines are expected to induce protective immune responses mediated by CD8＋ T cells, targeting the hepatocytes infected with early sporozites or merozoited just before release. The roles of antigen-specific antibodies , INFgamma, CD4＋ T cells and CD8＋ T cells will be investigated,
and the immune responses after challenge the immunized
mice with sporozites and merozites will be compared.

３
９

14C-08) SIGNALING MOLECULES RESPONSIBLE FOR THE EXCYSTATION
AND METACYSTIC DEVELOPMENT OF ENTAMOEBA INVADENSASAO MAKIOKA１, MASAHIRO KUMAGAI１, SEIKI KOBAYASHI２, TSUTOMU TAKEUCHI２
１

Dept of Tropical Medicine, Jikei Univ School of Medicine, Tokyo, Japan
Dept of Tropical Medicine and Parasitology, Keio Univ School of Medicine, Tokyo, Japan

２

Using an axenic excystation system in vitro, we examined the effect of protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3K), which are signaling molecules responsible for numerous cellular responses, on the excystation and metacystic development of Entamoeba invadens.
Excystation, which was assessed by counting the number ofmetacystic amoebae after the induction of excystation, wasinhibited by PKC inhibitors, staurosporine, chelerythrine
chloride and calphostin C, in a concentration-dependent
manner during incubation compared to the controls. As cyst
viability was not affected by these inhibitors, reduced ex-

cystation was not due to their direct toxic effects on cysts.
Metacystic development, when determined by the numberof nuclei in amoeba, was delayed by these PKC inhibitors,
because the percentage of 1-nucleate amoebae was lower
than in controls at day 3 of incubation. Wortmannin, a potent inhibitor of PI3K, also inhibited excystation and metacystic development of E. invadens in a concentrationdependent manner compared to the controls. These results
indicate that signaling through PKC and PI3K contributes
to the excystation and metacystic development of E. invadens.

14C-09) POSTTRANSLATIONAL LIPID MODIFICATION OF RAB PROTEINS BY A PROTEINGERANYLGERANYLTRANSFERASE TYPE II FROM ENTAMOEBA HISTOLYTICAASAO MAKIOKA１, MASAHIRO KUMAGAI１, TSUTOMU TAKEUCHI２, TOMOYOSHI NOZAKI３
１

Dept of Tropical Medicine, Jikei Univ School of Medicine, Tokyo, Japan
Dept of Tropical Medicine and Parasitology, Keio Univ School of Medicine, Tokyo, Japan
３
Dept of Parasitology, Gunma Univ Graduate School of Medicine, Maebashi, Japan２

The small GTPase Rab proteins function as a molecular switch of intracellular vesicular transport. They need to
be posttranslatinally geranylgeranylated by a protein
geranylgeranyltransferase type II (GGT-II) and also to be
associated with a Rab escort protein (REP) to attach themembrane of intracellular transport vesicles and function.
To clarify biochemical properties, we cloned GGT-II and
REP from Entamoeba histolytica (Eh) and characterized
the recombinant proteins. Alpha and beta subunits of
EhGGT-II and EhREP, consisting of 317, 315 and 480
amino acids, had the conserved domains and showed 14-34,
42-49 and 18-23% identity with those of other organisms,

respectively. Also, EhGGT-II and EhREP were phylogenetically independent of those of other organisms. Recombinant EhGGT-II, which was purified as a heterodimer of
two subunits, showed enzymic activity only in the presenceof EhREP when assayedusing EhRab5 as a protein substrate. There was difference in substrate activity among
EhRab proteins. EhGGT-II showed difference in substratespecificity compared to rat GGT-II. Further study will bedone to evaluate the biological significance in difference between E . histolytica and mammalian GGT-II and REP and
the possibility of the enzyme as a drug target against amebiasis.

４０Workshop C-2
14C-10) ARTESUNATE-AMODIAQUINE COMBINATION THERAPY IN UTAN, SUMBAWA, INDONESIAHIROJI KANBARA１, YOES P. DACHLAN２, SUKMAWATI BASUKI２, Y. ISKANDAR３, K. ZEINUDIN３
１

Inst Trop Med, Nagasaki Univ, Nagasaki, Japan
Tropical Disease Center, Airlangga Univ, Surabaya, Indonesia
３
Utan Rhee Health Center, Sumbawa, Indonesia

２

In the malaria control project that was implemented in
Utan area of Sumbawa island from November 2002 to October 2004 under JICA partnership program, we found highprevalence of chloroquine resistant Plasmodium falciparum(P. f.) there. We requested the central government to introduce a new drug combination to this area, and got the permission to make the trial of Artesunate-Amodiaquine combination therapy. We received the drug combinations for 50
adults from the ministry of health, Indonesia. The teams forcase detection and treatment were the same as those during
the control project. They visited subvillages in the area, detected P. f. patients using ICT Malaria P. f. / P. v. diagnostic
kit from clinically suspected malaria cases, and adminis-

tered the new combination drugs to them after obtaining
their informed consent. The efficacy of the drugs was examined by the follow-up study for 28 days. Complete cure wasobtained in 60% patients after two days of treatment, 95%
after 7 days and 100% after 14 days. No serious side-effects
were seen during the first three days of treatment when theteams monitored. This combination was effective to asexual
stage of parasites but not to matured sexual stage of parasites (gametocytes), which remained in blood for several
days after disappearance of asexual forms but much shortercompared with remaining periods of gametocytes after
chloroquine treatment. These results supported the alteration of the old drugs to the new combination.

14C-11) NEW ANTIMALARIAL ENDOPEROXIDE MECHANISM OF ACTION AND DEVELOPMENT
OF RESISTANCE USING PLASMODIUM FALCIPARUM, IN VITRO
S. M. ALY NAGWA, HYE-SOOK KIM, YUSUKE WATAYA
Faculty of Pharmaceutical Sciences, Okayama University, Okayama, Japan

Resistance to antimalarial drugs is increasing nearly
everywhere in the tropical world, confounding global attempts to Roll Back Malaria. To combat the further spreadof resistance, it is generally accepted that there is an immediate need for new effective antimalaria drugs with adequate
knowledge of drug resistance mechanism. We developed
about 5000 new antimalarial candidates and among these
new antimalarial compounds we selected the most effective
endoperoxide, N-89. N-89 is a effective antimalarial drug
which showed high activity and selectivity. In this study wedescribe antimalarial activity of N-89 and cloning techniqueunder drug pressure to get the double benefits of obtaining

pure homogenous and resistant clone. We obtained Plasmodium falciparum clones resistant to a novel drug (N-89)
with four folds increase in EC５０ value and afford daily drugpressure concentration 2 x 10-６ M. Cross resistance to other
antimalarial drugs was also tested. No cross resistance wasobserved to other structurally related (artemisinin) andstructurally unrelated (quinine, chloroquine and mefloquine) antimalarial drugs. These parasite clones provide
useful material for investigating possible drug resistancemechanism. We are currently using these parasite clones inproteome analysis, which enable us to define specific proteins related to the action of N-89 drug.

４１

14C-12) NEW ANTIMALARIAL DRUG DEVELOPMENT −ANTIMALARIAL ACTIVITY AND
PHARMACOKINETICS OF ENDOPEROXIDE−YUKARI NAKASE１, NATSUKI TANIGAWA１, TOMOKO TANAKA１, HYE-SOOK KIM１, YUSUKE WATAYA１,
ARAKI MASUYAMA２, MASATOMO NOJIMA２, WU JINMING２, SATORU KAWAI３
１

Faculty of Pharmaceutical Sciences, Univ of Okayama,Okayama, Japan
２
Faculty of Engineering, Univ of Osaka, Osaka, Japan
３
Dokkyo University School of Medicine, Tochigi,Japan

Malaria is parasitic disease caused by protozoan of theparasite Plasmodium. Currently more than 1 million people
die of malaria each year. Unfortunately, the situation is getting worse with the emergence of multi-drug resistant Plasmodium species. Under the current circumstances without
effective vaccine, it is very important project to develop
new antimalarial drugs that can overcome the drug resistance. By the study of new antimalarial drug, we develop N89 [1, 2, 6, 7-tetraoxaspiro (7, 11)- nonadecane] to identify
potent antimalarial compound, which have cyclic peroxide
formation like existing antimalarial drug, artemisinin. We
examined the administration route which can be able to use
in a coma of severe malaria case, administration schedule toeffect a complete cure, and we also examined pharmacokinetics of N-89 by LC-MS. In an attempt to clinical use of N
-89, we administered N-89 twice only first day and once
daily for two consecutive days [75mg/kg/day, i.v.] when theparasite infection rate was 1%, and observed time-coursechanges in the infection rate. The parasite began to decrease

16 hours after the drug administration. The course wasmonitored for two months, and all five mice in the N-89
treatment group were completely cured. For the pharmacokinetics studies, blood samples were obtained sequentially after N-８９was administrated to rats or mouse by the
intravenous and oral routes. Concentrations of N-89 inplasma were determined by LC-MS after the pretreatmentof acetonitrile solution. During single i.v. administration [30
mg/kg] the plasma concentration level of N-89 was decreased rapidly depend on concentration of N-89. This pattern correspond to 2 compartment model, it means N-89
distribute in tissue immediately and then excrete into theblood slowly. Tmax time is 0.5 [i.v.] and these results weresame as we found in oral administration of N-89. We are
now investigating the pharmacokinetics, antiamlarial action
and general toxicity of N-89 to establish an appropriate administration method. In the conference, the current status of
the development of novel antimalarial drugs is introduced.

14C-13) A CONSIDERATION TO MECHANISM OF ANTI-MALARIAL DRUG ACTION
AND DRUG RESISTANCE CONSTRUCTIONYOSHIYUKI MIYATA１, SEIKI KOBAYASHI２, YUMIKO OSA３, MISAKO MATSUSHITA２,HIROSHI NAGASE３, TSUTOMU TAKEUCHI２
１

POLA Chemical Industries, Inc., Yokohama, Japan
Dept of Tropical Medicine, School of Medicine, Keio Univ, Tokyo, Japan３
School of Pharmaceutical Sciences, Kitasato Univ, Tokyo, Japan２

The world-wide-sprending drug-resistant malaria is aserious obstacle for Roll-Back-Program by WHO. We haveinvestigated the reduction of drug-resistance of malaria by
DSP (Dibenzosuberyl piperazine derivatives) to overcome
these drug-resistance-problem, which would inhibit thioltransporters such as MRP1. We have now found new effcts
by DSP, anti-malaria effects and qunine-resitance-reducing
effcts. Anti-malaria effect on BALB/c mice inoculated withchloroquin-sensitive P.chabaudi at dose of 5x10exp6, andresistance-reducing effect on BALB/c mice inoculated withchloroquin-resistant P.chabaudi at dose of 5x10exp6 was investigated. We revealed that DSP at dose of 20mg/Kg
shows antimalarial effect. And chloroquin-resistant P.
chabaudi had not only chloroquin-resistance but alsoquinine-resistance. DSP reduced both drug-resistance. Itmeans DSP would be able to reduce multi-drug resistanceof malaria.

４２

14C-14) ANALYSIS OF MUTATIONS IN CYTOCHROME b GENE OF PLASMODIUM FALCIPARUMISOLATES IN THAI-MYANMAR BORDERYASUKO NAOSHIMA-ISHIBASHI１,２, MORITOSHI IWAGAMI１, SHIN-ICHIRO KAWAZU１,SORNCHAI LOOAREESUWAN３, SHIGEYUKI KANO１,２,３
１

Dept of Approp Technol Dev Trans, Res Inst, Inter Med Ctr of Japan, Tokyo, Japan
２
Grad Sch Comprehensive Human Sci, Univ of Tsukuba, Ibaraki, Japan
３
Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

The combination of atovaquone and proguanil (MalaroneTM) has been established as a drug of choice to preventand treat multi-drug resistant Plasmodium (P.) falciparum
malaria in travelers. However several cases of resistanceagainst MalaroneTM have already been reported in someparts of Africa, and many of the cases are supposed to be
associated with mutations at the codon 268 of cytochrome bgene in mitochondria of P . falciparum. Atovaquone is supposed to act on cytochrome bc1 complex as a competitor of
ubiquinol, inhibits electron transport in mitochondrial inner
membrane and leads the parasite to death. Mutations aroundatovaquone-binding site in cytochrome b are supposed tocause atovaquone resistance. The objective of this study is
to estimate effectiveness of MalaroneTM on treatment, andprophylaxis for the travelers to Thai-Myanmar border wheremulti-drug resistant malaria is highly endemic.
Seventy P. falciparum samples taken from patientsfrom Thai-Myanmar border were sequenced to detect muta-

tions around the codon 268. Additionally other 4 codons in
atovaquone-binding domain 272, 275, 280, 284, whichwere supposed to be related to atovaquone resistance, werealso sequenced. All the 70 samples showed no mutations at
the codon 268 of cytochrome b gene. Sixty-one cases weresuccessfully sequenced for the other codons 272, 275, 280,
284, and they had no mutations.
In Asian countries, even in the multi-drug resistant areas in the great Mekong region, no case of MalaroneTM resistance has been reported clinically or genetically yet. The
more the usefulness of MalaroneTM increases for both treatment and prophylaxis, the wider the drug-resistance against
MalaroneTM may spread in the region. Though the total
number of investigated samples is not so large, we may conclude from these findings that MalaroneTM should be recommended for prophylaxis and treatment of malaria in
Mekong region by now.

14C-15) SCREENING FOR G6PD DEFICIENCY BY WST-8 METHOD (2): REACTIVITY
OF BLOOD-SPOTTED FILTERS COLLECTED IN MALARIA ENDEMIC COUNTRIESMEIJI ARAI１, FUMIHIKO KAWAMOTO２, HIROYUKI MATSUOKA１
１

Div. Med. Zool., Dept. Infect. Immun., Jichi Med. Sch., Tochigi, Japan
２
Div. of Int. Health, Inst. Sci. Res., Oita Univ. Fac. Med., Oita, Japan

WST-8 method is a simple and rapid G6PD-deficiency
screening method which can be used under field conditions.
This method is expected to be particularly useful for the onsite detection of partial G6PD-deficiency. Our recent laboratory evaluation revealed that not only whole blood but
also blood-spotted filters are suitable for the WST-8 method.
In the present study, blood-spotted samples collected in thefields were subjected to WST-8 method and the results werecompared with those of G6PD gene analysis. A total of 680
samples collected in the field surveys conducted in Vietnam,
Cambodia, Myanmar, and Indonesia, during 2003 and 2004,
were brought back to our laboratory and subjected to the

WST-8 filter method. Furthermore, 59 venous blood samples were obtained from those who had been judged as G6
PD-deficiency by the on-site WST-8test and agreed to give
additional blood for G6PD gene analysis. Among 680 samples, 49 (7.2%) were judged as highly deficient (HD), and55 (8.1%) were partially deficient (PD). Among 59 samples
analyzed for G6PD mutation, 4 were mutation homozygote(3 were HD and1was PD by WST-8 test), 30 were hemizygote (28 HD and 2 PD), and 19 were heterozygote (3 HD,
14 PD, and 2 cases of slightly deficient), suggesting that G6
PD activity obtained by the WST-8 method correlates nearlywith the genotype of G6PD mutation. On the other hand,４３

there were 49 cases judged as G6PD-deficiency (12 HD and
37 PD) by the WST-8 filter method, although their G6PD
mutation analysis had not been made. Even when we consider those who had not agreed additional blood taking orcases of young children, a significant number in the 53
cases might have been overlooked by the on-site G6PD test.

In order to establish efficient malaria control programs withusing gametocytocidal drugs such as primaquine, it is essential to improve the accuracy of the on-site G6PD test.
Therefore, we need to optimize the conditions of WST-8
method by both field- and laboratory-based studies.

４４Workshop D-1
14D-01) DISTILLING CLUSTERS FROM THE STATISTICS OF DENGUE IN VIETNAM
USING A KRIGING INTERPOLATION APPROACH
SUSUMU TANIMURA１, QUYUH LE MAI２, UYEN NIN TROUNG２, CHUSHI KUROIWA３, TSUTOMU MIZOTA１
１

Dept of Socio-environmental Medicine, Inst of Tropical Medicine, Nagasaki University, Nagasaki, Japan
２
Dept. of Virology, National Institute of Hygiene and Epidemiology, Hanoi, Vietnam
３
Dept Health Policy and Planning, School of International Health, Univ of Tokyo

A number of visualizing techniques for disease clustering have been proposed including statistical and mathematical modeling approach. The statistical modeling approaches
grasp an epidemic trend more effectively than mathematicalone especially when large geographic variation was observed in epidemic data. Amongst such statistical models,
kriging is the most suitable theory for geographic cluster
observation because it requires fewer arbitrary parameters.
Repeated outbreaks of dengue fever is a serious problem in
Vietnam. The objective in present study is to distill clustersof dengue fever with application of kriging spatial interpolation. Vietnam disease statistic provided the number ofclinic case of dengue fever by province from 1999 to 2003
with demographic data. Annual morbidity rates of dengue
fever by province were calculated, each of which was
linked to a geometric centroid of province. Estimates for
spatial interpolation were computed with normal kriging
model derived from the centroids with morbidity rate. On
the map spatially interpolated, clusters were especially ob-

served in the southern areas around Tay Ninh Province andthe central area around Gia Lai Province in 1999. The trend
in 2000 is almost same as 1999 except disappeared smallerclusters. Larger outbreak struck Vietnam in 2001. The southcluster moved slightly toward the ocean side, and the central cluster shifted slightly to the north. In 2002, the southcluster changed the position more closer to ocean side. And
in 2003, the south cluster reached the seashore in Ben Tre
Province and the central cluster shifted more to north. Spatial interpolation from centroid of province is essentiallydifferent from mapping colored with province boundaries; itmeans the interpolation ignores topographic or social
boundaries. Conversely, it rather preferable to understanding the global trend of dengue epidemics in this study. The
reason of moving cluster is yet to be clarified. It possibly
provides a clue to build a predictive model of dengue outbreaks. This study was supported by JSPS Core University
Program.

14D-02) MOLECULAR EPIDEMIOLOGY OF DENGUE VIRUS SEROTYPE 2 IN THE PHILIPPINESLEONORA T. D. SALDA１,２, MARIA D. C. PARQUET３, NOBUYUKI KOBAYASHI２, KOUICHI MORITA３
１

Graduate school (Ph.D. course), Nagasaki University, Nagasaki, Japan
２
Faculty of Pharmacology, Nagasaki University, Nagasaki, Japan３
Department of Virology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan

Background
Dengue fever has been occurring endemically in many
areas of the Philippines particularly in Metro Manila andother urban localities of the country. Of the four serotypes,
DENV 2 has been consistently detected in outbreaks/epidemics from 1995 to 2002. Only a limited data on the molecular epidemiology of DENV 2 in this country, however,is available. This study aims to determine the genetic variability of DENV 2 circulating locally and identify possible
associations between virus genetic subtype and severity ofclinical presentation.
Materials and Methods
A total of 41 strains from Dengue fever (DF), Dengue
hemorrhagic fever (DHF) and Dengue shock syndrome(DSS) patients between 1995 and 2002 were isolated. The
pre-Membrane (prM) and envelope (E) genes from these
isolates were sequenced and aligned for comparison. The
envelope sequence data were compared with 38 DENV 2 E
gene sequences from different geographic areas including
13 previously isolated Philippine strains available in Gen-

４
５

Bank.
Results
Phylogenetic analysis revealed that two distinct genotypes of dengue 2 virus are currently circulating in the Philippines. Asian 2 genotype was constituted mostly of earlier
isolates (48.0%) obtained from 1995 to 2002. Fifty-two percent of local isolates on the other hand were of Cosmopolitan genotype the majority of which were collected from1999 to 2002. None of the amino acid changes were consistent between DF and DHF/DSS samples and thus could not
be correlated with disease outcome.
Conclusion

The phylogenetic data suggests that DENV 2 strains
circulating in the Philippines are mainly of the Cosmopolitan genotype, displacing Asian 2 genotype over a short period of time since its introduction in 1998. Although no
consistent sequence differences were observed to distinguish isolates that may cause more severe disease, increased
pathogenicity may be caused by nucleotide changes in theviral genome other than the prM and envelope regions.
Collaborators
Ronald R. Matias and Filipinas F. Natividad (Researchand Biotechnology Division, St. Luke’s Medical Center,
Quezon City, Philippines)

14D-03) GENETIC ANALYSIS FOR SUSCEPTIBLE GENE TO DENGUE HEMORRHAGIC FEVER
IN VIETNAMLAN NGUYEN THI PHUONG１, MIHOKO KIKUCHI１, HUONG VU THI QUE２, NGU VU THIEN THU２,
THAM VO DINH３, DAT TRAN VAN４, HA DO QUANG２, KOUICHI MORITA５, KENJI HIRAYAMA１
１

Dept. of Molecular Immunogenetics, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan,２Arbovirus laboratory, Pasteur Institute Ho Chiminh City, Vietnam
３
Pediatric Hospital No. 2, Ho Chi Minh City, Vietnam
４Center for Preventive Medicine, Vinh long Province, Vietnam
５Dept. Virology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan

Dengue fever is getting a serious public health problem in many regions of the world, Almost１％of the patients with Dengue Fever (DF) develop Dengue Hemorrhagic Fever (DHF), or Dengue Shock syndrome (DSS).
Two factors are proposed to be important to produce DHF /DSS. One is viral virulence and the other is host genetic
factor. In this study, we made an experimental design to
identify the host gene (s) contributing to the development of
DHF / DSS in Vietnamese by case control study. The patients with DHF or DSS were clinically diagnosed by WHO
criteria, and their peripheral blood samples were collected
at the Center for Preventive Medicine, Vinh Long Province(VL), and the Pediatric Hospital No. 2, Ho Chi Minh City
(ND2) in 2002 to 2003. The patients age ranged between 10

months and 15 years. 200 age and sex matched control samples were collected in Vinh Long. The number of the patients with DHF cases was 20 from VL, 121 from ND2, andthat of the patients with DSS was 172 from VL, 159 fromND. DNA was extracted from each blood sample, then
HLA class I (HLA-A, B), class II (DRB1) and TNF-αpromoter SNPs typing were performed. There was no significant difference in HLA-A, HLA-B and TNF-αpromoter
SNPs alleles. However, HLA-DRB1*0901 was significantly
decrease in DSS. The DRB1*0901 allele might directly
contribute to resistance to DSS or might be a genetic marker
that has strong linkage disequilibrium with some resistant
gene.

４
６

14D-04) SEROEPIDEMIOLOGICAL STUDY ON HBV, HCV AND HIV INFECTIONSAMONG VOLUNTARY BLOOD DONORS IN LAO PDR
KAN TORIYAMA１, MASACHIKA SENBA１, PRAPAN JUTAVIJITTUM２, TE THAMMAVONG３, AMNAT YOUSUKH２
１

Dept of Pathology, Inst of Trop Med, Nagasaki Univ, Nagasaki, Japan
Dept of Pathology, Faculty of Medicine, Chiang Mai Univ, Chiang Mai, Thailand
３
National Blood Transfusion Center, Lao Red Cross, Vientiane, Lao PDR

２[INTRODUCTION] Southeast Asia is a highly endemic
area of HBV infection and also HCV infection in some regions. Not only HBV and HCV infections but also HIV infection is still raging in this area. However there are few
epidemiological reports of these blood-borne diseases fromLao PDR. [MATERIALS AND METHODS] The total
number of 4,739 serum samples from the first time voluntary blood donors (2003-2004, 17-64 years old; male: 3,400,
female: 1,339) in Vientiane area was examined for HBs-Ag,
anti-HCV and anti-HIV1/2. [RESULTS] 1) HBs-Ag positive rates by age; 17-20 years old: 9.1% (male: 10.6, femal:6.1%), 21-30 years old: 9.0% (male: 10.0, female: 5.4%),
31-40 years old: 5.7% (male: 6.1, female: 4.2%), 41-50
years old: 2.1% (male: 0.0, female: 10.3%), 51 years old
and over: 9.4% (male: 4.2, female: 25.0%) and total positive rate was 8.6%. 2) Anti-HCV positive rates by age; 1720 years old: 0.6% (male: 0.6, female: 0.7%), 21-30 years
old: 1.2% (male: 1.2, female: 1.2%), 31-40 years old: 2.3%

(male: 2.5, female: 1.4%), 41-50 years old: 2.1% (male: 1.7,
female: 3.4%), 51 years old and over: 3.7% (male: 4.2, female: 0.0%) and total positive rate was 1.0%. 3) Anti-HIV1/
2 positive rate. Only 2 cases of male, 28 and 42 years old
respectively, showed positive and total positive rate was
0.04%. [CONCLUSION] Our findings suggest that Vientiane area of Lao PDR belongs to a high prevalence region
group of HBV infection by WHO classification and HBV
infection is predominant more than HCV infection at thepresent stage. However due to the biological characteristics
of HCV, a high tendency to progress to chronic diseases andhepatocellular carcinoma, HCV infection will become amore important medical problem in the near future. On HIV
infection, although the positive rate is very low at present, it
is concerned that the patients with HIV infection will rise in
number with the continuing increase of people exchange
among the neighbouring countries.

14D-05) INTER-CRF RECOMBINANTS (ICRS): DISCOVERY OF NEW CLASS OF HIV-1 RECOMBINANTS
AND ITS EPIDEMIOLOGICAL IMPLICATIONSYUTAKA TAKEBE１, XIAOJIE LI１, YANLING MA２, XUESHAN XIA３, SHIGERU KUSAGAWA１,
YUKO YOKOTA１, TOSHINARI ONOGI１, TEIICHIRO SHIINO１, YOSHIMI HOSHINA１,QIANQIU WANG１, TIN AUNG４, KHIN YI OO４, MIN THWE４１National Institute of Infectious Diseases, Tokyo, Japan
２
Kunmimg CDC, Kunming, Yunnan, PRC
３
Kunming University of Science and Technology, Kunming, Yunnan, PRC
４National AIDS/STD Prevention Programme, Yangon, Myanmar

Background: Diverse forms of HIV-1 recombinants appears
to be arising continually in previously identified geographical recombination hotspots found in Asia, including Yunnan
Province of China and Myanmar. We carried out the molecular epidemiological investigation to monitor the genetic
variability of HIV-1 strains and studied the detailed structural characteristics of HIV-1 recombinants emerging inthese areas.
Methods: We determined near full-length nucleotide se-quences of HIV-1 recombinants found in Myanmar andYunnan Province. Recombination breakpoint analyses, including, bootscanning, informative site and subregion tree
analyses, were performed to define their recombinant structure, and bootstrap values were used to confirm the subtype
assignments.
Results: We identified approximately 12% of HIV-1 strains
found among IDUs in southeastern Yunnan are the diverse
forms of inter-CRF recombinants between previously estab-４７lished CRF07_BC and CRF08_BC (n=5). Similarly, continued monitoring of HIV-1 strains in Myanmar identified thesecond class of HIV-1 inter-CRF recombinants comprisedof CRF07_BC and CRF01_AE (n=3)among24recent HIV-1
isolates in Yangon (in 2002-2004).
Conclusions: Mixing of different lineages of HIV-1 strains
in highly-exposed population leads to the evolution of newforms of HIV-1 recombinants and even the second-

generation recombinants between previously established
CRFs. In the present study, we identified two novel classes
of inter-CRF recombinants (ICR) between CRF07_BC and
CRF08_BC in Yunnan Province (China) and between CRF
07_BC and CRF01_AE in Yangon (Myanmar). This suggests the dynamic relationship of the epidemic in Asia. We
propose to designate these new recombinants as ICR01_
0708 and ICR02_0701.

14D-06) POSSIBLE RISK OF SALMONELLA INFECTION FROM MARKET FOODS
IN VIENTIANE CAPITAL, LAO PDRYUTAKA MIDORIKAWA１, SATOSHI NAKAMURA２, AKIRA SUGIYAMA３, SHIGEHIRO AKACHI３
１

Dept of Clinical Nutrition, School of Public Health Suzuka University of Medical Science Suzuka Japan
２
Research Institute, International Medical Centre of Japan３
Mie prefectural Institute of Public Health and Environmental Science

In Vientiane Capital of Lao PDR, occurrences of frequent cross contamination by food-borne bacteria species ofVibrio and Salmonella was pointed out at the last in Kitakyushu (Midorikawa et al., 2003). Salmonellosis is one of thecommonest but serious health problems in the developing
countries. Therefore, to clarify the actual situation of Salmonella contamination at some food markets in Vientiane isstill important. The study was conducted around 10 days
both in September (the rainy season) and in December (thedry season) in 2004. The bacteria were examined from thesurface of domestic animal and fish meats, some vegetables
and cookers available from the markets. A new method de-veloped by us (Midorikawa et al. 2004) was also employed
to detect Salmonella, in addition to classical Invic screening.
Four Salmonella species were recovered from 41 foods
samples (9.8%) and 6 Salmonella species were also recovered from stool samples of 39 healthy dwellers (15%) in therainy season. Salmonella contamination in food samples
was lower in the dry season. Salmonella sero-typing resulted in some common species between the foods and thestools samples. The genomic analyses of these strains are in
progress. The risk of Salmonella infection from market
foods will be discussed herein.

14D-07) PREVALENCE OF RESPIRATORY INFECTION CAUSEDBY STREPTOCOCCUS PNEUMONIAE AND HAEMOPHILUS INFLUENZAE
IN THE CAMPS OF TSUNAMI AFFECTED AREA IN SRI LANKAHIROSHI WATANABE１, WAKANA SAITO１, MARIKO SAITO１, CHIHARU KAJI１, KIWAO WATANABE１,KAZUNORI OISHI１, NOBUYUKI NISHIKIORI２, OSAMU KUNII２
１

Department of Internal Medicine, Institute of Tropical Medicine, Nagasaki University, Japan
Research Center for Tropical Infectious Diseases, Institute of Tropical Medicine, Nagasaki University, Japan２

Our objective was to investigate the status of acute respiratory tract infections caused by Haemophilus influenzae
and Streptococcus pneumoniae in tsunami disaster evacuation camps. Nasopharyngeal swabs (NP) of 324 internallydisplaced persons (IDP) in 3 different tsunami disasterevacuation camps of Sri Lanka were collected between

March 18 and 20, 2005 and analyzed for MIC, betalactamase production, serotypes, PCR and pulsed-field gelelectrophoresis (PFGE). The prevalence of at least one of
the following respiratory symptoms; snivel, sore throat,
cough and sputum were 84%, 70.5% and 64.7% in eachcamp. Twenty-one H. influenzae from IDP and 25 S. pneu-

４８

moniae from 22IDP were isolated from the NP. All H. influenzae isolates were nontypeable and 5were beta-lactamase
producing. Seventeen pneumococci were susceptible, 5showed intermediate resistance and 3 were fully resistant topenicillin G. molecular typing by PFGE showed the 21 H.
influenzae had 13 patterns and 25 pneumococcal strains had
16patterns. Each of the 2 different patterns of H. influenzae
were detected in 2 or 3 IDP in camps 1 and 3. Different

PFGE patterns of serotype 3 and 22A pneumococci weredetected in 2 or 3 IDP in camp 1, and those with serotype 9
A, 10A and 11A were detected in 2 IDP in camp 3. Ourdata indicate acute respiratory tract infections caused byvarious types of H. influenzae and S. pneumoniae appear tohave been prevalent, some of which were transmitted fromperson to person in tsunami disaster evacuation camps.

14D-08) PHENOLYC GLYCOLOPID-1 (PGL-1) IN TISSUES INFECTED BY MYCOBACTERIUM ULCERANS
MASUMI SHIMIZU-SUGANUMA1１, M MWANATAMBWE２, S ETUAFUL３, K ASIEDU４, NOBUAKI AKAO５,
KAZUHIRO SHICHINOHE１, GORO ASANO６
１

Dept of Laboratory Animal Science, Nippon Medical Sch, Tokyo, Japan
２
Dept of Pathology, Kinshasa Univ. Kinshasa, Congo
３
Agroyesum St Martin Hospital, Ashanti, Ghana
４
Global Tuberculosis Program, WHO, Geneva, Switzerland
５
Environmental Parasitology, Tokyo Medical and Dental Univ, Tokyo, Japan
６
Hakujikai General Hospital, Tokyo, Japan

Mycobacterium ulcerans is the causal agent of Buruli
ulcer, a disease recently highly prevalent in some part of Africa. The world wide endemic distribution of the disease isbeing revised due to change in investigative strategies for its
detection. Ulcers is the most advanced lesion of the disease,although other forms like papules, plaques, edema and nodules exist. The causal agent of Buruili ulcer, Mycobacterium
ulcerans is close to Mycobacterium tuberculosis and Mycobacterium leprae. In this work, we have investigated thepresence of Phenolyc Glycolipid-1 (PGL-1), a carbohydrate- based antigen, generally known as specific to Mycobacterium Leprae in tissue infected with Mycobacterium ulcerans . The potential use of this antigen for early detection of
the disease, a key factor to preventing progress to aggravated stages, has prompted this work.Materials and MethodsSkin flaps were surgically obtained from 30 patientsclinically diagnosed as Buruli ulcerat the AGROYESUMHOSPITAL in ASHANTI COUNTRY OF GHANA where
BuruliUlcer is endemic.

Results
Clinical form
PlaquesNodules
Ulcerated nodules
Deep ulcer bed
Healing ulcer

Patients
3
10
1
7
9

Acid fast bacilli Stain (+)
1
5
0
4
2

Acid fast bacilli stains: Fite-Faraco & Harada stains./
PGL-1: Phenolyc glycolipid- 1CONSIDERATIONS 1/The
above results suggest that PGL-1 may not be specific to one
member of the mycobacterium genus and that mycobacte-

PGL-1 (+) by immunostain
1
5
0
4
2

rium ulcerans wall probably expressthe antigen. 2/Whatrole exactly Phenolyc glycolipids play in the pathogenesisof this ulcerative disease should be further investigated.

４
９

Workshop D-2
14D-09) LATENT INFECTION OF MALARIA PARASITES IN SCHOOL CHILDREN LIVING
IN THE ENDEMIC ARIA IN VIETNAM
SHUSUKE NAKAZAWA１, DAO LE DUC２, TUAN NGUYEN VAN２, HARUKI UEMURA１,
GIANG NGUYEN DUC２, KAZUHIKO MOJI１
１

Dept of Protozoology, Institute of Tropical Medicine, Nagasaki University
２
National Institute of Malariology, Parasitology and Entomolofy

Detection of asymptomatic carriers of parasites andcomplete treatment of them is one of essential measures inmalaria control, because they are potentially healthy gametocyte carriers. We have been noticing that even school children have high titer of anti-parasite antibodies an that theyharbor malaria parasites without any malaria symptoms inour study site in Vietnam. Furthermore, there were tendency
that when a school child was diagnosed as malaria by microscopy, its brothers and sisters were also infected withparasites. These imply that there should be parasites carriersin the vicinity of infected people and that microscopic negative should not be true negative. We compared PCR diagnosis with microscopic diagnosis on the blood samples fromthe endemic area to confirm whether microscopic examination grasps real situation of malaria infection. After obtaining a written informed consent of the parents we collectedblood from school children in Phu Thuan, Binh Phuoc
Province one time a week over five weeks in a rainy season
in 2003. Slide-positive children with P.f at week 0 and at thefirst time during the study period were regularly treatedwith artesunate according to the policy of Vietnam. Vivax
malaria was regularly treated with chloroquine and primaquine. When school children turned to be slide-positive
again, they were given CV8 according to the policy. The
prevalence by microscopy was 36% by microscopy and thatby PCR was 61% against malaria infection. That was 27
and 47% against falciparum malaria. P.v, P.o, and P.m weremore fluently detected by PCR than by microscopy. These
infections were detected as mixed infection with other species. When PCR diagnosis was a golden standard, specificity of microscopy was 100%. Sensitivity of microscopy,
however, 60%against malaria, 50% against falciparum malaria, and occasionally reduced to be 10%. In several cases
we observed that parasites remained one week after treatment by PCR. On the other hand, we noticed that parasites
disappeared and changed to other species without any treatment. The results suggest that parasite number should fluctuate sub-microscopic level and that PCR negative should
not be true negative although it sensitivity was higher thanthat of microscopy.

14D-10) SCHOOL BASED MALARIA EDUCATION IN MEKONG SUB-REGION
JUN KOBAYASHI１,２, HIRONORI OKABAYASHI１, SHIGEYUKI KANO２, SOUMEI KOJIMA３,TUTOMU TAKEUCHI４, SEIKI TATENO１
１

Bureau of International Cooperation, International Medical Center of Japan, Tokyo, Japan
２
Research Institute, International Medical Center of Japan
３
Center of Medical Science, International University of Health and Welfare
４
Faculty of Medicine, Keio University

Malaria education in a primary school has alreadybeen recognized one of the health education strategies inmalaria control among Mekong countries. Asian center ofinternational parasite control (ACIPAC), which was conducted by Thailand and Japan technical cooperation, has developed the concept of the strategy and the field model. The
concept of school based malaria education was developedon the basis of health promoting school, which has beenemphasized by WHO. Especially, cooperation between
school and community was strengthened in the concept.
Teachers in the model schools in Thailand conduct thehealth education using by participatory learning action approach to promote schoolchildren to play important roles as
messengers for malaria prevention in the community. ACI-

５０

PAC has introduced the concept on the international training course and several international and domestic conferences in the Mekong sub-region from 2002. In Thailand, theschool based malaria education in the elementary school
has been conducted in not only ACIPAC model area but
also several provinces located in Thai- Myanmar border,
where malaria is still public health problems. In Cambodia,
the malaria education has been started as a national programsupported by Global fund. ACIPAC trainees have developed
the proposal. In Myanmar, malaria education has already in-cluded one of topic on the curriculum in the elementary
school. Small scale pilot project supported by ACIPAC wasstrengthened this program including in participatory learning approach. The policy maker in the government was recognized the approach in the malaria control and school
health. Moreover, the importance of the intra-sector cooperation in the malaria education was recognized as a global
strategy among the member nation in World Health Assembly, 2005.

14D-11) PREVALENT DISTRIBUTION OF KOBE-SSURDNA-TYPE-BABESIA MICROTI IN RODENTS
IN THE SOUTHERN PART OF MAINLAND OF CHINA AS WELL AS TAIWANATSUKO SAITO-ITO１, MASATOSHI KASAI１, MIDORI KASAHARA１, ATSUKO KAWAI１, YASUHIRO YANO２,
ENG-RIN CHEN３, XIAO-HANG MA４, NOBUHIRO TAKADA２
１

Sec of Parasitol, Dept of Genome Sciences, Kobe Univ Grad Sch of Med, Kobe, Japan
２
Dept of Pathol Sci, Fac of Med, Univ of Fukui, Fukui, Japan
３
Dept of Parasaitol, Kaohsiung Med Univ, Kaohsiung, Taiwan
４
Col Life Sci, Zhejiang Univ, Zhejiang, China

Most cases of human babesiosis have been reported in
the United States of America (USA) and in Europe. Cases
have been mainly caused by Babesia microti, a rodent babesia, and Babesia divergens, a bovine babesia, in the USA
and Europe, respectively. In Asia, a few cases of humanbabesiosis were reported in Mainland of China (Yunnan, Inner Mongolia and Zhejiang), Taiwan (Chiayi) and Japan(Hyogo). The etiological parasites of all cases in Mainlandof China have not been clearly identified. The etiologicalbabesia of the Taiwanese case was only shown to be serologically related to B. microti. The Japanese case wascaused by blood transfusion from an asymptomatic donor
who resided in Awaji Island, Hyogo. The SSUrDNA sequence of the etiological babesia (Kobe type) was most homologous but not identical to that of B. microti originatedfrom endemic regions of the USA (US type).
As we previously reported, Otsu type-B . microti (another SSUrDNA-type of Japanese B. microti) is widely distributed in rodents in Japan, while Kobe type-B. microti
seems to be localized in a few certain regions, so far in
Awaji Island and in Aomori Prefecture. US type-B. microti
was found in Sapporo, Hokkaido. On the other hand, in Taiwan, Kobe type-B. microti was identified in Kaosiung andNantour. Taiwanese Kobe type-B. microti was differentiatedfrom Japanese Kobe type-B. microti by the internal transcribed spacer 1 and 2 (ITS1/ITS2)sequences.
We started the survey in the southern part of Mainlandof China (Fujian and Zhejiang) in 2005. B. microti was detected in 14 (Niviventer confucianus13; Apodemus agrarius
1) of 31 rodents by thin blood smear observation and/or
PCR. The SSUrDNA sequences of B. microti parasites in
13 rodents were completely identical to Kobe typeSSUrDNA. The ITS1/ITS2 sequences of the 13 parasites
were more similar to those of Taiwanese Kobe type-B. microti than those of Japanese Kobe type-B. microti. The
SSUrDNA and ITS1/ITS2 sequences of the parasite in therest one N. confucianus rodent were different only by two
nucleotides (one in the SSUrDNA sequence and one in the
ITS1/ITS2 sequences) from those of Japanese Kobe type-B.
microti.
It was demonstrated for the first time that Kobe type-B.
microti was widely distributed from the southern part ofMainland of China, Taiwan to Japan, where Asian humanbabesiosis cases so far emerged. The finding suggests that
Kobe type-B. microti may play an important role in emergence of human babesiosis in Asia.

５１

14D-12) IDENTIFICATION OF CAUSATIVE PARASITES OF LEISHMANIASIS IN PAKISTANBY CHYTOCHROME b GENE ANALYSISHIROSHI UEZATO１, HIROTOMO KATO２, BHUTTO AM３, SOOMRO FR４, MEMON MZ５, TAREEN MI６,
TAREEN IK７, KEN KATAKURA８, SHIGEO NONAKA９, YOSHIHISA HASHIGUCHI１０
１

Dept of Dermatology, University of Ryukyus, Okinawa, Japan
Dpt of Veterinary Hygiene, Faculty of Agriculture,Yamaguchi University, Yamaguchi, Japan
３
Dept of Dermatology, Chandka Medical College Hospital, Larkana, Sindh, Pakistan
４
Leishmaniasis Office, Chandka Medical College Hospital, Larkana, Sindh, Pakistan
５
Dept of Dermatology, Civil Hospital Sukkur, Sukkur, Sindh, Pakistan,６
Dept of Dermatology, Saleen Medical complex, Quetta, Pakistan
７
Dept of Dermatology, Sandeman Provincial Hospiral, Quetta, Pakistan
８
Lab of Parasitology, Dept of Disease Control, Veterinary of Medicine, Hokkaido University, Hokkaido, Japan
９
Dept of Dermatology University of Ryukyus, Okinawa, Japan１０
Dept of Parasitology, Kochi Medical School, Kochi University, Kochi, Japan
２

Pakistan, located in Middle-East Asia, is one of endemic areas of Leishmaniasis. The causative parasites ofLeishmaniasis in Middle-East Asia reportedly include L.
(L.) major and L. (L.) tropica. During the three-year period
from January 2003 to December 2004, we diagnosed andtreated patients with Leishmaniasis who lived in Pakistan.
We identified the causative Leishmania parasites by cytochrome b gene analysis using biopsy specimens and cultured parasites collected from the patients.
Subjects and methods: Sixty patients (40 males and 20
females) with Leishmaniasis in Pakistan were diagnosed byclinical symptoms, histological findings, Giemsa staining,
separate culture, and other methods. The ages of the patients ranged from 5 months to 50 years with the average of
20.7 years. The methods to identify the causative parasites
were as follows: 1) extraction of DNA from the biopsy
specimens and/or cultured parasites; 2) PCR with consensus
primers of Leishmania cytochrome b gene; 3) direct se-quencing of the amplified PCR products to determine thebase sequences for identification of the parasites.
Results: There were 46 cases of L. (L.) major and 13
cases of L. (L.) tropica and one unknown case. 45 cases of
L. (L.) major were found in Larkana city located in Indus
Valley and in the area surrounding Sukkur city. 12 cases of
L. (L.) tropica and one case of L. (L.) major were found in
Quetta city, a mountainous region near Afghanistan.
Discussion: The number of cases of Leishmaniasis in
the vicinity of Larkana city increased rapidly from 16 in
1996 to 300 in 2001. This provoked a public health problem(Bhutto AM et al, Int J Dermatol, 42: 543, 2003). However,no reports have been identified the causative parasites inthis area. The present study revealed that most of the patients with L. (L) major were found in Indus Valley, andthose with L. (L.) tropica were distributed in a mountainous
region near Quetta city.

14D-13) PREVALENCE OF LEISHMANIA DONOVANI SPECIFIC URINARY ANTIBODY
IN A COMMUNITY IN BANGLADESH
MOHAMMAD ZAHIDUL ISLAM１, MAKOTO ITOH１, MD. ANWAR UL ISLAM２, A. R. M. SAIFUDDIN EKRAM３,
HIDEKAZU TAKAGI１, YOSHIHISA HASHIGUCHI４, EISAKU KIMURA１
１

Dept of Parasitology, Aichi Medical Univ, School of Medicine, Aichi, Japan
２
Dept of Pharmacy, Univ of Rajshahi, Rajshahi, Bangladesh
３
Dept of Medicine, Rajshahi Medical College, Rajshahi, Bangladesh
４
Dept of Parasitology, Fac of Medicine, Kochi Univ, Kochi, Japan

Visceral leishmaniasis (VL), after passing 100 years
from its clinical descriptions by Leishman and Donovan in

1903, the status of the disease has been upgraded to “mostneglected” disease from its traditional position as simply a５２“neglected” disease. Approximately 90% of the 500,000 estimated new annual cases of VL occur in rural areas of
Bangladesh, India, Nepal, Sudan, and Brazil. Very few studies have been reported on prevalence of VL in Bangladesh.
Recently, we have developed methods to detect Leishmania
antigen specific antibodies in urine samples: ELISA using
acetone treated antigen (urine ELISA) and recombinantkinesin-related protein with a molecular weight of 42-kDa(rKRP42 urine ELISA) for the diagnosis of VL, whichshowed almost the same sensitivity and specificity as withserum samples. We have applied these methods in a village
named Nobai Bot Tala with a population of 527, in Godagari Thana, Rajshahi district, to determine the prevalence of
L. donovani specific antibody among the populations. During our1st visit in March 2005, we registered 302 volun-teers in our study and collected urine samples after getting
their informed consent. We got 14.6% (44 positives/ 302) L.
donovani specific antibody positive among the volunteers,of which 45.5% (20/44) male and 54.5% (24/44) female.
Among the 44 positives 9 were previously treated for VL,
and the rest had no past VL history. All the cases who wereclinically suspected and positive by our test (s) were advised to visit to Rajshahi Medical College Hospital(RMCH) for better clinical evaluation and treatment. In our
2nd visit in July 2005, we collected 454 urine and serum
samples from the previously and newly registered volunteers. We will discuss the occurrence of clinical cases
among the antibody positives, changes of antibody titeramong treated cases, and also the incidence of L. donovani
specific antibody among the study populations.

14D-14) EPIDEMIOLOGICAL STUDIES ON HUMAN CUTANEOUS LEISHMANIASIS IN SRI LANKA
CHIZU SANJOBA１, MASAAKI OKAMOTO１, NANA ARAKAKI１, OZBEL YUSUF２,
ALTEN BULENT３, YASUNOBU MATSUMOTO４, TAKESHI AGATSUMA５,
R.R.M.L.R. SIYAMBALAGODA６, R.P.V.J. RAJAPAKSE７, YOSHITSUGU MATSUMOTO１
１

Department of Molecular Immunology, School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan
２
Faculty of Medicine,Ege University, Izmir, Turkey
３
Faculty of Science, Hacettepe University, Ankara, Turkey
４
Department of Global Agricultural Sciences, School of Agricultural and Life Sciences,
University of Tokyo, Tokyo, Japan
５
Department of Environmental Health Science, Graduate School of Medicine, Kochi Medical School, Kochi, Japan
６
Anti-Malaria Campagin, Department of Health, Colombo, Sri Lanka
７
Department of Veterinary Medicine and Animal Science, University of Peradeniya, Sri Lanka

Cutaneous leishmaniasis cases have recently increased
throughout Sri Lanka since the first case was reported in
1992. Epidemiology of leishmaniasis in this country however has still been unclear. An epidemiological research has
been performed since 2003 in Anuradhapura, Kurunegala,and Matale district in Sri Lanka to identify pathogenic species and investigate clinical features. Skin aspirates from 57
clinically suspected cutaneous leishmaniasis patients were
cultured in NNN medium, and Leishmania promastigotes
were detected in culture form 20 out of 57 patients. Using
Sri Lankan isolated parasites, the nucleotide sequences of aregion of the actin-encoding gene, which is highly conserved among eukaryotes, was analyzed. The actinencoding gene from the Sri Lankan isolate was comparedwith those from the reference strains of L. major and L.
donovani. Sri Lankan isolate differed by only 1 bp from L.
donovani while Sri Lankan isolate and L. major differed by
34 bp. The PCR products of the mini-exon gene, which is

unique in the genus Leishmania, were compared with thoseof reference strains of L. donovani, L. major, L. tropica and
L. amazonesis. Interestingly, Sri Lankan isolate yielded two
products of different sizes which is same products patternwith L. donovani, which is the principal pathogenic speciesof visceral leishmaniasis. The skin lesions of patients fromwhom Leishmania parasites were detected occurred in exposed areas like the face, arms, and legs, and were 5-20 mm
in diameter. Some lesions lasted 4 to 10 months as blister inappearance. All patients were negative in Kalazar detect
dipstick for visceral leishmaniasis (InBios International Inc.,
Seattle, USA), which is antibody detection assay to rK39
antigen and highly sensitive for visceral leishmaniasis
caused by parasite members of the L. donovani complex.
ELISA using the same rK39 antigen showed that the opticaldensity value of plasmas from 11 patients obtained in 2004
were low (0.30±0.2) compared with positive control (3.06),
although that of negative control (Japanese healthy volun-

５３teer) was 0.1±0.09. Those results suggest that human indigenous cutaneous leishmaniasis caused by the parasites

belonging to L. donovani complex is endemic in Sri Lanka.

14D-15) NEEM OIL AS BIOLOGICAL CONTROL AGAINST PHELEBOTOMINE SANDFLYYUKIKO WAGATSUMA１, INDRANI DHAR２, MOHAMMAD SHAFIUL ALAM３, HAMIDA KHANUM３,
M.A. WAHED２, RASHIDUL HAQUE２
１

Department of Epidemiology, Graduate School of Comprehensive Human Sciences,
University of Tsukuba, Ibaraki, Japan２
ICDDR, B: Centre for Health and Population Research, Dhaka, Bangladesh
３
Department of Zoology, University of Dhaka, Dhaka, Bangladesh

Objective: The study aims to evaluate the effect ofneem oil against Phlebotomus argentipes.Methods: This
study was conducted in a kala-azar endemic area of
Mymensingh, Bangladesh. CDC miniature light traps wereused for the baseline collection of sandflies from the dwelling houses. Traps were set at 17:00-18:00 hours and collected at 5:00-6:00 hours on the following day. A total ofbaseline 72 trappings was made. Among the baseline
houses, 30 houses were selected on a basis of abundance ofsandflies. Neem oil solution with detergent emulsifier was
sprayed on the house wall in a concentration of 100 ml/m2.
Control houses were sprayed with only detergent solution.

Effects of neem oil on sandflies were evaluated by trappingson the 3rd and 7th days. Results: A total of 1,005 sandflies
were collected from single night collection; 657 were males
and 348 females from 98 screened houses. Neem oil withdetergent was sprayed on 18 houses and 12 houses were
only sprayed with detergent. Significant reduction in sandfly number was observed among neem oil sprayed houses
compared to the control houses (76% and 41% reduction respectively). Conclusion: This study demonstrated the effectof neem oil solution application on wall for reducing thenumber of sandfly. Further study requires confirming thelonger duration of the effect.

５４Workshop C-3
15C-01) PRELIMINARY STUDIES ON THE EFFECT OF T CELL- AND INFLAMMATORY CYTOKINESON MUCIN-RELATED GENE EXPRESSION IN INTESTINAL EPITHELIAL CELLSKAZUTOSHI TAKEDA, KATSUMI HASHIMOTO, MINORU YAMADA, RYUICHI UCHIKAWA,TATSUYA TEGOSHI, NAOKI ARIZONO
Department of Medical Zoology, Kyoto Prefectural University of Medicine, Kyoto, Japan

Regulation mechanisms of the mucus production andsecretion induced by intestinal nematode infection still remain to be elucidated. We examined the effect of sodium
butyrate (NaB) and various cytokines (IL-4, IL-13, IL-17,
IL-6, TNFα and IL-1β・on gene expression of mucin- andglycosylation-related genes in rat small intestinal epithelial
stem cell-derived cell line IEC-6.
[Method] Semi-confluent IEC-6 cells cultured in the internal wells of 24-well double chamber dishes with DMEM
medium containing 5% FCS and 5µg/ml insulin at 5% CO2
atmosphere were used throughout the study. After adding
NaB (final 1 mM) and incubating for 24 hours, cytokines
were added and IEC-6 cells were further incubated for another 24 hours. cDNA was synthesized after collecting total
RNA form IEC-6 cells, and real-time PCR was performed.
Genes examined were mucin core peptide (MUC) 2, MUC5
AC, goblet cell specific peptide trefoil factor family (TFF) 3,

resistin-like molecule (Relm) β, one of sialyltransferases,
Siat4c, and one of sulfotransferases, 3ST1.
[Result] Addition of NaB in the culture medium resulted inmarked upregulation of TFF3: 20-times higher than cultures
without NaB. In cultures incubated with NaB and further
added with Th2 cytokines IL-4 or IL-13, gene expression of
Siat4c and 3ST1was markedly upregulated. Addition of pro-inflammatory cytokine IL-6 following NaB administration
showed a mild upregulation of MUC2. Other cytokies, IL17, TNFα or IL-1β showed no significant effect on gene expression of IEC-6 cells.
These results indicated that NaB stimulates IEC-6 cells
to express TFF3, one of secretory molecules expressed inmature goblet cells. Th2 cytokines IL-4 and IL-13 might alter mucin- or membrane glycoprotein-glycosylation status
by upregulating sialyl- and sulfo-transferases.

15C-02) MECHANISM OF MUCOSAL PROTECTION AGAINST NEMATODE INFECTION:
ALTERED EXPRESSION OF GOBLET CELL- AND MUCIN GLYCOSYLATION-RELATED GENES
IN THE INTESTINAL EPITHELIUM IN RATJUNKO YAMAUCHI１，２, YUICHI KAWAI１, MINORU YAMADA１, RYUICHI UCHIKAWA１,TATSUYA TEGOSHI１, NAOKI ARIZONO１
１

Department of Medical Zoology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Department of Gastroenterology, Kyoto Prefectural University of Medicine, Kyoto, Japan

２

Although mucus response is considered to play an important role of mucosal protection against damages incurredby pathogens, it has also been suggested to be responsible
for the rejection of nematodes from the intestine.
To investigate whether there were alterations of the expression of goblet cell-and mucin glycosylation-related
genes during nematode infection, epithelial cells were isolated from the small intestine of Brown Norway rats andmast-cell deficient Ws/Ws rats after Nippostrongylus brasiliensis infection, and gene expression levels of 3 types of
mucin core peptides, 3 types of glycosyltransferases and 3

kinds of non-mucin peptides were determined by semiquantitative reverse transcription (RT)-PCR.
Among the genes investigated, mucin core peptide(MUC) 2, trefoil factor family (TFF) 2, TFF3 and sialyltransferase (Siat) 4c were up-regulated as early as 2-4 days
post-infection. Seven days post-infection, up-regulation of
MUC3, MUC4, resistin-like molecule (Relm) β and 3Osulfotransferase (3ST) 1 was observed, while 3ST2 expression levels increased after worms were expelled. This resultshows that expression levels of each goblet cell-and mucin
glycosylation-related genes altered differently along the５５

course of infection indicate progression of sequential qualitative changes in mucus properties after infection.
Similar alterations of gene expression were ob-served in Ws/Ws rats, suggesting that mast cells in the epithelium are not relevant to up-regulation of these genes.

15C-03) PROTECTIVE IMMUNITY AGAINST H. NANA ONCOSPHERES IS ESTABLISHED INDEPENDENTTO KNOWN APOPTOSIS REGULATORY MOLECULESKOTARO ONISHI１, KAZUHITO ASANO２, KENJI ISHIWATA１, NAOHIRO WATANABE１
１

Dept of Tropical Medicine, Jikei Univ., Tokyo, Japan
２
Dept Physiology (I), Showa Univ, Tokyo, Japan

Host’s intestine is important on the host resistance toorally infectious parasites. However, immune system to intestinal parasites is yet unclear. Mice receiving a single oral
inoculation of Hymenolepis nana (H. nana) eggs acquire astrong protective immunity and a challenge infection witheggs will be completely rejected by inhibiting larval growthin the intestinal villi. This strong resistance to re-infection isestablished on 24hours after immune infection. This acquired immunity is dependent on CD4 positive cells. We focused our studies on in vivo analysis of the role of apoptosis
regulatory molecules in host defense mechanisms against H.
nana re-infection in mice. Primary infection of H. nana
was carried out by giving 1000 eggs on day 0. The mice
were challenged orally with 1000 eggs on day 5 and killed

4 days later. The protective effect was assessed by counting
the cysticercoids which had developed in the intestinal villi
by day 9, 4 days after challenge. Monoclonal antibodies
were intraperitoneal injected at 0.5mg on 2 hours before
challenge infection. These antibodies are blocking monoclonal antibodies against mouse Fas L, TNF and CD40 L.
Treatment of neither antibodies on protective immunity
failed to suppress acquired resistance to H. nana reinfection. Fas knock out mice were carried out as above infection. In this knock out mice, protective immunity also
failed to suppress acquired resistance. The present results
suggest that protective immunity against H. nana oncosphere is established independent to known apoptosis regulatory molecules.

15C-04) SCHISTOSOMIASIS HAEMATOBIA: DIFFICULTY OF URINATIONYOSHIKI AOKI１, MITSURU HAMAMOTO２, KANJI WATANABE１, NGETHE MUHOHO３
１

Department of Parasitology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan
２
Graduate School of Social Sciences, Hitotsubashi University, Kunitachi, Tokyo, Japan３
Kenya Medical Research Institute, Nairobi, Kenya

Hospital-based studies report that most patients infected with Schistosoma haematobium, present varying
symptoms when they pass the urine. The present study was
attempted to quantify the difficulty in micturition of schoolboys, aged from 9 to 16 yrs old, in an endemic area ofschistosomiasis in Kenya. The boys were examined for theeggs in urine and for the bladder pathology. Among theboys who passed the eggs, 46 boys, 23 with bladder pathology and 23 without pathology, were then questioned on the
difficulty in micturition by International Prostate Symptoms
Score (IPSS) and by a questionnaire on dysuria. And they
were examined for the voiding function by the portable uro-

flow meter. Since the difficulty in micturition may principally be due to the bladder pathology, the results of ourstudies were compared between boys with and without thepathology. The average of the grade of bladder pathology of
23 boys (WHO standard) was 2.6. There was no difference
in intensity of infection between the boys with and without
the pathology (61.2 and 58.6 eggs/ 10ml of urine). IPSS
over 8 manifests the difficulty in micturition. The mean and
SD of IPSS of boys with the bladder pathology was 15.4±
5.9 and those of boys without pathology was 12.7±9.4.
The passing of urine is usually accompanied by burning andpainful micturition. There was no difference in frequency of５６dysuria between the boys with and without the pathology.
Pain is felt over the suprapublic region and near the end of
urination. Pain is characterized by the sense of a pricking or
sharp and cutting pain. Uro-flow meter showed the significant difference in the voiding function between the boys
with and without the pathology. T to Q max (sec) and Q
max/ V void of the boys with the pathology were 7.4 and1.97. The corresponding values of the boys without the pathology were 11.0 and 1.43. The results of uro-flow meter
indicates that the boys with pathology urinate more powerfully or urgently than those without the pathology. The present study offered some clarification on the difficulty in
micturition.

５
７Workshop C-4
15C-05) USEFULNESS OF URINE-ELISA WHICH DETECTS FILARIA SPECIFIC IGG4:A SURVEY IN JIANXI, CHINA
MAKOTO ITOH１, ZHIHONG LI２, WEIPING WU３, DEJIAN SUN３, EISAKU KIMURA１
１

Dept of Parasitology, Aichi Medical Univ School of Medicine, Aichi, Japan
２
Jianxi Prov. CDC, Jianxi, China
３
Chinese CDC, Shanghai, China

In China, lymphatic filariasis was widespread in 16 outof 36 provinces/autonomous regions/municipalities (P/A/
M) in 1950s. Number of the patients was estimated to be 31
million. Following National Filariasis Control Program, thepositive rate of the disease was decreased to less than 1% in
all endemic areas by 1994. Then Ministry of Health declared ‘basic elimination’ of filariasis. By 2001, Ministry of
Health declared ‘true elimination’ of filariasis in eight P/A/
M where microfilaria positives had not been found for 10
years. For declaration of ‘true elimination’ in the rest eight
P/A/M, huge number of night blood samples must be examined. Our survey in Zhejiang Province in 2002, where 2,800
residents were examined with a urine based ELISA for filarial antigen specific IgG4, suggested usefulness of the
ELISA to assist the confirmation of ‘true elimination’. In
this survey, we examined 8,046 urine samples from students
of 57 schools in Gaoan, Jiangxi Province using the urine
based ELISA. Microfilaria (mf) positive rate in Gaoan was

4.5% before a filariasis control program launched in 1971.
Mass drug administration by DEC salt was made in 1999.
Microfilaria positives have not been detected since 2002.
Brugia pahangifemale antigens were used to detect filarial
antigen specific IgG4 in the urine samples by ELISA.
Among 8,046 urine samples examined, 8,016 (99.6%) were
negative with the urine ELISA. Twenty-eight samples werepositive but most of them showed low antibody titers. Students with the urine ELISA positives were examined inblood mf, blood antigen (by ICT) and urine based ELISA
again; all tests showed negative results. As the filariasis
control program progressed and number of symptomatic filariasis patients decreased, it become difficult of obtain collaboration of residents, especially for a night blood mf survey. The urine based ELISA uses urine samples collected at
daytime and can examine a large number of samples in ashort period. The urine based ELISA is a useful tool forevaluation of filariasis control program.

15C-06) INTESTINAL PARASITIC INFECTIONS IN SCHOOL CHILDREN IN A SUBURBAN AREA
OF HANOI, VIETNAM
SHOJI UGA１, THI VIET HOA NGUYEN２, LE KHANH THUAN２, SHINICHI NODA３, YASUNORI FUJIMAKI４１

Dept of Med Technol, Faculty of Health Sci, Kobe Univ School of Medicine, Kobe, Japan
２
National Institute of Malariology, Parasitology, and Entomology
３
Research Center for the Pacific Islands, Kagoshima University, Kagoshima, Japan
４
Department of Parasitology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan

An epidemiological study on intestinal parasitic infections among school children in a suburban area of Hanoi,
Vietnam, was conducted. Of the 217 school children involved in this study, 166 (76%) were positive for at least
one of nine species of parasite (six helminths and three protozoa). Among the helminth parasites, Trichuris trichiura(67%) was detected the most frequently followed by Ascaris lumbricoides (34%) and hookworm (3%). In the caseof protozoan parasites, Entamoeba coli (8%) was the mostfrequently detected followed by E . histolytica (2%). No
Cryptosporidium parvum or Cyclospora sp. were found. A
questionnaire survey revealed that there was no positive relationship between parasite infection and the children’s
school records, educational background or parental income,which have been known to play a role.

５
８

15C-07) STUDY ON TRANSMISSION AND INFECTION OF SOIL-TRANSMITTED NEMATODE
IN THE SUBURB OF HANOI, VIETNAM: CONTAMINATION
OF WATER AND AIR WITH PARASITE EGGSSHINICHI NODA１, THI VIET HOA NGUYEN２, SHOJI UGA３, LE KHANH THUAN２,YOSHIKI AOKI４, YASUNORI FUJIMAKI４
１

Research Center for the Pacific Islands, Kagoshima University, Kagoshima, Japan
National Institute of Malariology, Parasitology, and Entomology, Hanoi, Vietnam
３
Department of Medical Technology, Faculty of Health Sciences, Kobe University School of Medicine, Kobe, Japan
４
Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan２

We are carrying out an epidemiological study on a soil
-transmitted helminth infection in a village located in thesuburb of Hanoi, Vietnam. We have already reported thatthe soil, dust, vegetables, and fingers and nails were contaminated with parasite eggs. In the present study, we attempted to detect parasite eggs in water and air samples. In
the study area, the well water was used for daily life, andrain water is also used in some households. The examination of water and air was conducted in the rainy season(June-August) and the dry season (December-February).
Two litter water samples were collected from 29 households,
two schools, two kindergartens, one restaurant, two ponds,
one lake and 23 ditches. The examination showed that

13.8% of water samples from households and all water
samples from ponds, lake and ditches were contaminatedwith parasite eggs in the rainy season. In the dry season,
10.7% of water samples from households and all water
samples from ponds, lake and ditches were also contaminated with parasite eggs. The detection of parasite eggs in
air was attempted at 156 points (50 points in the house, 88
points outside of the house and 18 points of utility pole).
The transparent sticky tape (5x20 cm) was put for two
weeks. In the rainy season, parasite eggs were found at
4.9% of the points outside of the house, but parasite eggs
were not found in the dry season.

15C-08) STUDY ON THE INTESTINAL PARASITE INFECTION AMONG SCHOOL CHILDRENIN LUANGPRABANG PROVINCE, LAO P.D.R
KANAKO YAMAMOTO１, HIROYUKI AMANO１, TAKAAKI ISHIDA１, CHIKA KURODA２, NOBUHIRO KAWAGUCHI２,
KEO SISAYTHONG２, VIRASACK BANOUVONG３, VIENGSAVANH PHANMANIVONG４,
SOMMONE PHOUNSAVATH４, TOSHIMASA NISHIYAMA１
１

Department of public health,KANSAI Medical University
２
Luangprabang Provincial Hospital, LAO.P.D.R
３
Luangprbang Province Mararia Center
４
Department of Curative Medicine, MOH.LAO.P.D.R

In developing countries, the infections of the intestinal
parasites (Ascaris lumbricoides (As), Trichuris trichura(Tt), Hookworms (Hw) and so on) are common diseases
and these diseases are very important problems for thehealth conditions of school children. However in developing countries, the eradication of these parasites is not easy.
In this report, we would like to show the best procedure forthe treatment of intestinal parasites to the school children in
Luangprabang Province, Lao P.D.R. According to theguideline of Lao Ministry of Health, a single dose of mebendazole 500mg is recommended for the treatment method

against intestinal parasites. But the stool examination of after treatment is not usually done. Therefore, the effects ofmebendazole treatment are not evaluated correctly. In thisresearch, we tried to treat with mebendazole for all childrenof several schools in Luangprabang Province and evaluatedthe effect of the mebendazole made in Lao PDR and Thailand. One thousand five hundreds twenty four stool specimens, which were collected from 2,397 school children (11primary schools) in Luangprabang from September 2003 to
May 2005, were examined by Kato’s cellophane thicksmear technique. On the other hand, the stool examination

５
９

was performed for 640 school children at the before andthree weeks after treatment with mebendazole. In this treatment, we used three different manufactures of mebendazoles, made in the factory A in Laos (A), the factory B in
Laos (B) and the factory in Thailand (T), and we tried two
procedures, one was the treatment by a single dose of 500
mg mebendazole (A-500, B-500 and T-500 regime), and another was two-times dosage regime of 250mg once a day
for consecutive 2 days (A-250 and B-250 regime).
In the results of before treatments, egg positive rate in
1,524 school children was 93.0% (As 74.5%, Tt 59.6%, Hw
29.8%, Opisthorchis viverrini 1.1%, Taenia spp. 0.2%), andmixed infection rate was 51.4%. The cure rates of As infection comparing with pre- and post-treatment were over 90%
by all methods. On the other hand in Tt infection, B-250
was 30% (T-500, A-500, A-250, B-500 and B-250 were33.3%, 32.1%, 27.8%, 28.6% and 58.1%, respectively). The
cure rates of Hw infection were 40% (T-500), 43% (A-500),
72.2% (A-250), 42.9% (B-500) and 46.4% (B-250). These
results suggested that A-250 regime was the most effective
against intestinal parasites in these procedures. In the future,
we are going to study to obtain the most suitable treatment
methods for the intestinal parasites in Lao PDR.

15C-09) STUDY FOR MEBENDAZOLE IN LAO PDRTAKAAKI ISHIDA１, KANAKO YAMAMOTO１, HIROYUKI AMANO１, KENJI FUKUNAGA２, PHOUNSAVATH SOMMONE３,
PHANMANIVONG VIENGSAVANH３, TOSHIMASA NISHIYAMA１
１

Dept of Public Health, Kansai Medical Univ, Osaka, Japan
Labolatory of Food and Nutritional Sciences, Faculty of Engineering, Kansai Univ, Osaka, Japan
３
Ministry of Health, Lao PDR

２Introduction: In our department, therapeutic study ofthe intestinal parasite infections, such as roundworm, whipworm, hookworm was conducted on the school children of
Luangprabang Province in Lao P.D.R., from 2003, and themebendazole was administered. Based on the therapeutic
guideline of intestinal parasite infection of ministry ofhealth, Lao P.D.R., 1 time administration of mebendazole 1
tablet (500mg) was carried out. There may be the dispersionof effect in the difference among the mebendazole of each
pharmaceutical company. This time, we examined the quality of the medicine of each pharmaceutical company. We
used the mebendazole available in 2 kinds of domesticproduct (made in Lao P.D.R.): A and B, 3 kinds of foreignproduct: C (made in Vietnam), D (made in Thailand) and E(made in Malaysia). In total, we were able to get 5 kinds ofmebendazole tablets in Lao PDR. Actual mebendazole content in the tablet of each pharmaceutical company wasmeasured. Methods: Each tablet was crushed by the mortar,and dissolved in the 0.05% formic acid/ 99.5% isopropanol
as 500µg/ml. By analyzing from molar absorption coefficient ε=15000 (312nm; 0.05% formic acid/ 99.5% isopropanol solution), the absorption value of 312nm was meas-

ured by the absorbance meter. Each 5 tablets of the pharmaceutical company were measured. Results: It was analyzed
from the absorption value, and the content of mebendazolein 1 tablet (500mg) were as follows. A: 563.3±8.0mg, B:
676.7±24.0mg, C: 543.3±11.7mg, D: 356.7±6.3mg, E:
413±8.0mg (Mean±SD). Therefore, it was proven that A,
B and C sufficiently contained mebendazole in 1 tablet. The
content of mebendazole in D and E were little. On the character of the tablets, C and D were crushable by usual mortar.
And, the tablet of B was very easy to smash. A and E weredifficult to be crushed (It was physically very firm). Simultaneously, we also got the result of being very characteristic
for the property of the tablet of each pharmaceutical company. Discussion: It was important for the mebendazole efficacy to spread easiness to worm directly, since it was notalmost absorbed in the gastrointestine. In addition to actual
mebendazole content, the character of the tablets, for example, the easiness of the tablet to dissolve may influence theeffect of the treatment. We are going to further examine thecharacter of mebendazole tablets of each pharmaceuticalcompany.

６０

15C-10) PARAGONIMIASIS IN LAO PDR.
SHIGEHISA HABE１, SATOSHI NAKAMURA２, PETER ODERMATT３, TRAN DUC SI３, DUONG VEASNA３
１

Dept of Microbiology and Immunology, School of Med., Fukuoka Univ., Fukuoka, Japan
２
Research Institute, International Medical Centre of Japan, Tokyo, Japan
３
Institut Francophone de Medicine Tropicale, Vientiane, RDP. Lao

Despite of some known cases among refugees outsideof Lao PDR, no detail human paragonimiasis research was
conducted in these two decades. Yet, no study was performed to identify the species of Paragonimus in the second
intermediate host crabs in the country. Therefore, the investigation was performed to clarify this relationship using
available crab samples at the central market places and at
the northern rural part of Vientiane Capital where paragonimiasis infection had been confirmed. A total of 312 crabs
contained 3 genera with 4 species were examined. No
metacercaria was recovered from the market obtained 2 Somaniathelpusa spp. (291 and 9 dissected). In the infested
area, 100% and 20% of metacercariae infection were con-firmed at Potamiscus sp. (7) and Parathelpusa sp. (5), respectivety. In the former crab, 681 metacercariae contained
578 large (L), 99 middle (M) and 4 small (S) size types
ones were observed. These metacercariae were mostly distributed in the muscles of there host crabs. The L and M
type metacercariae were identified as P. harinasutai and P.
bangkokensis, respectively on the basis of their morphological features of metacercariae and adult worms recoveredfrom the experimental dogs. S type and a metacercariae
from Parathelpusa sp. were identified as P. heterotremus and
P. westermani, respectively on the basis of their morphological features of metacercariae.

６１Workshop D-3
15D-01) MEASUREMENT OF XANTHURENIC ACID IN ANOPHELINE MOSQUITORYUTA HATTORI, YUICHI KASAHARA, HAJIME YOSHIDA, MEIJI ARAI, HIROYUKI MATSUOKA
Division of Medical Zoology, Department of Infection and Immunity, School of Medicine, Jichi Medical University

Xanthurenic acid (XA), a lateral reaction product oftryptophan metabolism in the omochrome pathway of eyepigment synthesis in insects, induces Plasmodium gameogenesis. Previously we reported that XA is present in mosquito salivary glands and that mosquito ingests saliva into
the midgut during blood feeding. Taken together, it is likelythat XA is discharged with saliva during blood feeding andis swallowed to the midgut where it affects Plasmodium gametocytes. In this study, we used a high performance liquid
chromatography with electrochemical detection (HPLCECD) to detect and quantify XA. We succeeded to measure

XA content in each individual mosquito. One larva or pupa
contained 20-50 nanograms (ng) of XA. One female adultcontained 10-50 ng of XA. We also measured XA contents
in mosquito tissues. The head contained about 70% of XA
in the whole body. It is likely because XA is a lateral product of omochrome. The midgut contained 0.1-0.2 ng. The
salivary gland contained 0.28±0.05 ng. After blood feeding,
XA contents in the salivary gland reduced to 0.13±0.06 ng(P<0.05). We suspect that mosquitoes consume saliva with
XA on blood feeding and some amount of XA might beswallowed to the midgut.

15D-02) RELATIONSHIP BETWEEN MALARIA TRANSMISSION EFFICACY AND THE AMOUNT OF
XANTHURENIC ACID IN ANOPHELINE MOSQUITOHAJIME YOSHIDA, YUICHI KASAHARA, RYUTA HATTORI, MEIJI ARAI, HIROYUKI MATSUOKA
Division of Medical Zoology, Department of Infection and Immunity, School of Medicine, Jichi Medical University

We succeeded to develop HPLC-ECD method formeasuring xanthurenic acid (XA) in mosquito. We canmeasure XA amount in each individual mosquito. A female
adult 7 days after emergence contained 10-14 ng of XA anda male adult contained 4 ng. We collected female mosquitoes when they emerged and measured XA at 2h, 48h, 96hand 240h after emergence. XA contents were highest at 2h
after emergence (52 ng) and reduced after that. At 240h XA
content was 10 ng. We measured XA in the salivary glandand found 0.35 ng at 48h and 0.10ng at 240h. We let twogroups of mosquitoes feed on the same mouse infected with
Plasmodium berghei. One group was 2-3 days mosquitoes
after emergence (young group), and another group was 1012 days mosquitoes (old group). Twelve days later, we
counted the number of oocysts developed on the midgut.
The mean numbers of oocysts were 85 in the youngt groupand 25 in the old group. This difference of oocyst number
might due to the difference of XA amount swallowed to the
midgut.

15D-03) ROBUST EXPRESSION OF A FOREIGN GENE IN THE SALIVARY GLANDS
OF ANOPHELINE MOSQUITOESHIROYUKI WATANABE, SHIGETO YOSHIDA, HIROYUKI MATSUOKA
Div of Medical Zoology, Dept of Infection and Immunity, Jichi Medical School, Tochigi, Japan

Malaria sporozoites invade the mosquito salivary
glands and remain in the salivary duct until they are injectedwith the saliva into vertebrate hosts during blood feeding.
The specific mechanisms by which Plasmodium parasites

６２

infect the salivary glands remain largely unknown. The purpose of this study was to establish robust salivary glandspecific gene expression in transgenic anopheline mosquitoes and to provide a potential tool for investigatingmosquito-parasite interactions. To this end, we obtained asalivary gland-specific promoter from upstream of a geneencoding a saliva protein. A promoter-reporter construct,consisting of the salivary galnd-specific promoter, the Discosoma sp. red fluorescent protein (DsRed) reporter gene,and the Antryp1 polyadenylation signal, was inserted into
the Minos transfer vector and transformed into the germline of Anopheles stephensi embryos. We generated transgenic A. stephensi mosquitoes that specifically express

DsRed in their salivary glands. Using advanced 3D confocal
microscopy, we showed robust expression of DsRed undercontrol of the salivary gland-specific promoter in the distallateral lobes of the salivary glands, where the sporozoites
invade preferentially, in a living mosquito as well as in dissected salivary glands. Furthermore, by using GFPexpressing sporozoites, we could observe the parasites passing through the salivary glands from the outer surface.
These results open up the possibility of elucidating theprocess and molecules involved in the salivary glandparasite interactions, and may lead to the development oftransmission-blocking strategies by using genetically modified mosquitoes that express anti-parasitic genes.

15D-04) TRANSGENIC ANOPHELINE MOSQUITOES EXPRESSING LECTIN
FORM MARIN ORGANISM IMPAIRE
IN TRANSMISSION OF A MALARIA PARASITEYOHEI SHIMADA１, DAISUKE KONDO１, YOSHIAKI KOUZUMA２, SHIGETO YOSHIDA１
１

Div of Medical Zoology, Dept of Infection and Immunity, Jichi Medical School, Tochigi, Japan
Department of Resource Biological Science, School of Agriculture, Ibaraki Univ, Ibaraki, Japan

２

When a mosquito ingests a blood meal from an infected host, Plasmodium gametocytes transform into gametes that mate and differentiate into zygotes and then ookinetes (elongated motile zygotes). Ookinetes cross the midgut epithelium and differentiate into oocysts, which after 10-15 days liberate sporozoites cross the salivary gland epithelium. Recent advances in the genetic engineering ofanopheline mosquitoes have raised hopes for their use as
new strategies for malaria control and provided a powerfultool to investigate mosquito-parasite interactions. Our research on transmission blockade using transgenic mosquitoes has been focused on the midgut stage of the parasites,
interfering with ookinete invasion or oocyst differentiation.
The molecule that we have introduced into a transgenic
mosquito is CEL-III isolated from Cucumaria echinata(Marine invertebrate). CEL-III has strong hemolytic activity
as well as haemaggrutination activity as a lectin. CEL-III

gene expression was driven by the carboxypeptidase promoter, midgut specific promoter. As expected, CEL-III expression was induced in the midgut at 6h after a blood meal.
Since CEL-III can hemolyze human and rat red blood cells,
but not mouse red blood cells, we established rat-P. berghei
infection model to address the transmission blocking efficacy of the CEL-III transgenic mosquito. We fed control
and transgenic mosquitoes on the same infected rat andmeasure the numbers of oocysts formed. The transmission
blocking efficacy of the transgenic mosquitoes was 91%, ascompared with control mosquito. Thus, expression of CELIII in the mosquito midgut severely reduced vector competency by inhibiting Plasmodium development. Because
CEL-III targets to red blood cells but not the parasites, we
anticipate that this CEL-III transgenic mosquito will be able
to impair parasite development of all Plasmodium species.

６
３Workshop D-4
15D-05) A REVIEW OF THE SEMINARS FOR TROPICAL MEDICINE AND HYGIENE IN KINKI REGION
TAIJIN KAKU１, MITSUAKI NISHIBUCHI２, YOSHITSUGU NAKAGUCHI２,TOSHIMASA NISHIYAMA３, TAKAAKI ISHIDA３
１

Department of Microbiology, Graduate Schoool of Medicine, Kyoto University, Kyoto, Japan２
the Center for Southeast Asian Studies, Kyoto, Japan
３
Public Health Department, Kansai Medical University, Moriguchi, Japan

We organized “the seminars for tropical medicine andhygiene in Kinki Region ” once in every 4 to 6 in the last
three years. The aims of the seminars are 1. To provide theopportunity for the researchers in Kinki Region to get exposed to various study fields and to promote their communication. 2. To provide the opportunity to learn tropical
medicine from the lecturers invited from outside of Kinki
Region. 3. To provide practical knowledge of tropical medicine for clinicians and researchers who have experience towork in the field in tropical areas. 4. To help clinicians andrelated medical staffs who wish to work in the tropical areas
in future to contact with researchers working in tropical
medicine. With these aims, we have been trying to make theseminars not only as the place of academic discussion but
also as an informal place where everyone can attend andspeak without hesitation. We held the first seminar in October 2002 with Nishibuchi and Nishiyama as official organizers. The title of the lecture in the seminar was “The present status and preparations for Malaria”. We held seminars
eight times so far at the Center for Southeast Asian Studies,
Kyoto University and Kansai Medical University in turns

usually with two or three lecturers at a time. The followings
are the subjects and the numbers (in parenthesis) of the lectures: malaria (3); bacterial infections including Vibrio infection (1), tuberculosis (1), and Hansen disease (1); viral
infections including AIDS (1), Arbovirus infection (1),
Ebola (1), and SARS (1); mosquito-related diseases (1);field medicine (1), medical care conditions in Laos (4), Bolivia (1), and others (2). We spent enough time to discusseach presentation. Due to limitations in selection of the lecturers there were too many lectures on Laos and no lecture
about non-malaria parasitic infections which are very important in tropical area. We should find some ways to solve
this problem in the future. The number of the participants
was 25.1 on average (range: 18 to 30) per seminar including
9.9 medical doctors, 2.2 nurses and 2.4 medical students.
We hope to have more participants from the medical fieldother than doctors. We are confident that we provided good
opportunities for the participants to communicate friendly
even after seminar. We will do our best to make this seminar
more fruitful.

15D-06) THE TREND OF NEW HIV INFECTIONS AND PATIENTS IN SAKU CENTRAL HOSPITALYOSHIHIRO TAKAYAMA, TOMOKO KOBAYASHI, SHUNYA FUKUOKA, SACHIKO OZAWA,MASANORI TEI, KUNIHIKO OKADADivision of General Medicine, Department of Medicine, Saku central hospital, Saku, Japan

Preface: The Committee on Trends in AIDS reports that a
combined total number of 1165 people newly suffered fromHIV infections and AIDS in 2004. By prefecture, Nagano
Prefecture ranked second in the number HIV carriers after
Tokyo. A tabulation of new reported AIDS patients asagainst the population rate shows that Nagano came on topof the list. It is expected that the number is great particularlyin the eastern part of Nagano Prefecture. The prevalence islooked upon as having been triggered by the influx of for-eigners who came en masse for the construction of the Nagano Shinkansen bullet railway line and expressways andfor construction projects for the 1998 Nagano Olympic
Games. Here, an attempt will be made to show trends in thenumber of newly infected patients at the Saku Central Hospital, located in the Prefecture’s eastern district, and how
the prevalence of HIV stands there.
Results: Our hospital had 74 new HIV carriers from October 1986 to July 2005. They included 47 AIDS patients

６
４(63.5%). The number of patients newly infected with HIV
stood at 9 cases in 2004 and 7 cases in January through Julyin 2005. Of them, those who suffered from AIDS totaled 7(77.8%) in 2004 and 6 (85.7%) in January through July in
2005. By nationality and gender, the infected had consistedof 8 Japanese men (22.2%), 1 Japanese woman (2.8%), 9
male foreigners (25.0%) and 18 female foreigners (50.0%)
before 1999. Since 2000, they have been made up of 26
Japanese men (68.4%), 2 Japanese women (5.3%), 3 maleforeigners (7.9%) and 7 female foreigners (18.4%). The infection routes were heterosexuality for 62 patients (83.8%),
homosexuality for 2 patients (3.2%), drugs for1patient(1.6%), blood preparations for 1 patient (1.6%), and mother-to-child transmission for 1 patient (1.6%).
Discussion: There have been signs of a rapid rise in thenumber of new HIV carriers, and things have begun totaken on a serious aspect in which HIV is increasingly carried to Japanese men primarily from foreign women. As relations with opposite sex are responsible in most cases with
infections, there is fear for an upswing in the prevalence of
HIV infections among Japanese women. Unless convincing
measures for the prevention of HIV infections are taken
now, they will inevitably sweep the eastern part of Nagano
Prefecture in several years.

15D-07) SUMMARY AND PROBLEMS OF TRAINING COURSE FOR DIAGNOSISOF OPPORTUNISTIC PROTOZOAN INFECTIONS ASSOCIATED WITH AIDSTSUTOMU TAKEUCHI１, NAOKI ARIZONO２, MOTOHIRO ISEKI３, TSUNEZO SHIOTA４１

Dept of Tropical Medicine and Parasitology, School of Medicine, Keio Univ, Tokyo, Japan
Dept of Medical Zoology, Kyoto Prefectural Univ of Medicine, Graduate School of Medical Sciences
３
Reserch of Parasitology, Kanazawa Univ, Graduate School of Medical Sciences４
Dept of Clinical Parasitology, Louis Pasteur Center for Medical Reserch

２

We conducted a training course for improvement in the
diagnostic techniques and related aspects on opportunistic
protozoan infections with the target of medical doctors/
technical personnels in the AIDS network hospitals forthese 6 years till 2002 by the financial support from MHLW.
This was primarily based on the observation that diagnosis
of such infections seemed unsatisfactory due to insufficient
education and training as well as rather rare opportunity toencounter these protozoan infections. However, such protozoan infections as amebiasis and toxoplasmosis have been
increasingly important in clinical aspects of AIDS. Since

2003, we have expanded the target for training to personnels in general hospitals in addition to the AIDS network
hospitals designated by MHLW because of increase in thenumber of HIV positive cases in our country. For this purpose, we have revised the style and media of announcementof training course and tried to establish the system for selfevaluation and self-motivation by utilizing CD-ROM andthe network consultation system. In this presentation, welike to summarize current status of this training course anddiscuss some essential problems to improve such approaches.

15D-08) SIMULATIONS ON SARS OUTBREAK IN JAPAN USING THE MATHEMATICAL MODELAYAKO FUKUTOME１，２, TOMOHIKO NISHINA１, TIANTIAN CHEN１, KAZUTOSHI FUJITA１, HIROFUMI ISHIKAWA１
１

Dept of Human Ecology, Okayama Univ, Okayama, Japan
Dept of Hygine & Preventive Med. Okayama Univ, Okayama, Japan２

We had a worldwide outbreak of the severe acute respiratory syndrome (SARS) raised from Hong Kong inMarch, 2003. In Japan, 52 susceptible cases as well as 16
possible cases of SARS-infected patients had been reported
from hospitals although no Japanese had consequently been

decided as SRAS-infected patients. However, we Japanese
can never negate the possibility that SARS will invade andsweep over Japan. It is therefore important to investigate thespread of SARS under an epidemic in Japan in an attempt
to devise effective measures against SARS. The two re-６５markable risk factors of SARS-transmission are wellknown; one is super-spreader events (SSE), another is socalled “close contact”, especially in hospitals. In this study,
we applied mathematical stochastic models based on theserisk factors for the simulation of the events of SARS transmission in Tokyo 23 wards of Japan. In the SSE invasion
model, the initial patient expands SARS to 15 people within
only one day. In the nosocomial transmission model, thetransmission is influenced by the period until when SARSinfected patients are sequestered. One SARS-infected patient transmits SARS to 20 persons under no sequestration.
The daily numbers of new incidents and prevarent cases
were simulated in each model. The periods from infection
to onset, from onset to admission, from admission to discharge and from admission to death referred to the previous
case reports and were fitted by Gamma distributions. Our
SSE invasion model shows that the maximum expecteddaily numbers of new incidents and prevarent cases are 51
and 782 people, respectively, for the case of a SSE invasion,
while they are 8 and 126 people for a non-SSE. In nosocomial model, they are 4 and 27 people for the case of 6days of non-isolation of SARS-infected patients and 19 and
121 people for 12 days of non-isolated situation respectively. In Tokyo 23 wards there are 64 beds in negative pressure rooms available. Our models indicate that patients fillthem entirely on the 17th day in the case of 12 days -nonisolation of nosocomial model, as well as on the 20th day
for the case of a SSE invasion and on the 35th day in caseof a non-SSE invasion in SSE invasion model. It is important for prevention of expansion of SARS infection both tofind out SARS infection at immediate early days and devise
measures against the transmission of SARS as soon as possible.

15D-09) TRAVEL MEDICINE OF GENERAL PRACTICE IN JAPANAKIHIRO HITANI１，２, EIICHI OKUZAWA１, ATSUO HAMADA１
１

Japan Overseas Health Administration Center, Yokohama, Japan
Medical Institute Zenjinkai, Health Care Center, HEALTHCHECK２

Not received

15D-10) HOW WELL TRAVEL CLINICS ARE KNOWN AMONG TRAVEL AGENCIESSHINJI FUKUSHIMA１, EIICHI OKUZAWA１, YASUTAKA MIZUNO２, NOBUYOSI TAKAHASHI３, ATSUO HAMADA１
１

Japan Overseas Health Administration Center, Yokohama, Japan
２
Travel Clinic, International Medical Center of Japan
３
Visitors Industry Institute, JTB Communications, INC

As internationalization increases, and overseas travel
becomes more affordable, the number of Japanese travelers
is growing. Despite the risk of contracting new diseases, oraggravating chronic disorders, Japanese travelers show little
concern about health matters. The purpose of this survey
was to ascertain how well travel clinics are known among
Japanese travel agencies.
[Methods]
We conducted a survey by sending a questionnaire to660 travel agencies belonging to the Japan Association ofTravel Agents (JATA) in March 2005. The following information was requested in the questionnaire.

１．Characteristics of travel agencies
２．How well travel clinics are known among travel agencies
３．How necessary travel agencies think travel clinics are.
４．Services travel agencies expect from travel clinics.
[Results]
60 travel agencies agreed to participate in this survey(participation rate of 9%).
(1) Characteristics of travel agencies: The average numberof clients per month was 4390. Main destination of their
tours was Asia (68.3%), Europe (8.3%), North America(6.7%), Oceania (3.3%). The duration of the stay was less６６than 7 days for many travel agencies (81.6%). Half ofTravel agencies had any organized tours for travelers withhealth problems. (aged 33.3%, disabled 18.3%, hemodialysis 8.3%, home oxygen therapy 3.3%)(2) More than half of the travel agencies were uinaware of
the existence of travel clinics.
(3) Approximately a quarter of travel agencies said theywould like to utilize travel clinics.
(4) The majority of travel agencies expected travel clinics toprovide them with medical information for travelers before they departed and wanted to be able to consult clin-

ics about health problems their clients experienced while
traveling.
A small percentage of travel agencies expected clinics
to administer vaccinations to travelers.
[Conclution]
The majority of them are unaware that travel clinics
exist and as a result, they expect very little from the clinics
at present. In the future, JOHAC would like to circulate information about travel clinics to promote their use. Japanneeds to be equipped with a system for dealing with travelers’health issues

15D-11) CHEMOPROPHYLAXIS ACCORDING TO THE GUIDELINES ON MALARIA PREVENTIONFOR JAPANESE OVERSEAS TRAVELERS
YASUTAKA MIZUNO１, IKUMI GENKA１, SHUZO KANAGAWA１, KOICHIRO KUDO１, SHIGEYUKI KANO１,２
１

Travel Clinic, Disease Control and Prevention Center, International Medical Center of Japan, Tokyo, Japan
２
Dept of Appropriate Technology Development and Transfer, Research Institute,International Medical Center of Japan, Tokyo, Japan

Mefloquine (Mephaquine Esu-Esu / Hisamitsu 275)
has been approved and registered as a chemoprophylaxis
against malaria since 2001 in Japan, and in March 2005, theguidelines on the prevention of malaria for Japanese overseas travelers was finally published by the group of specialists on malaria under the auspices of Japanese Society ofTropical Medicine and Ministry of Health, Labour and Welfare of Japan. Now, we have implemented the pre-travel
consultation on malaria as a part of travel clinic services in
the International Medical Center of Japan (IMCJ) since October 2004. We reported in this meeting the current situationof chemoprophylaxis against malaria according to theguidelines on the clients who came to our clinic. ThroughOctober 2004 to June 2005, 52 clients came to see us in ourclinic prior to their departure of travel abroad, asking chemoprophylaxis. According to the Guidelines, Mefloquine

was administered to 27 clients, of which 22 were definitely
thought to need regular chemoprophylaxis. Mefloquine was
not advised to the rest of the 25 clients, because the durations of their stays were too long to avoid possible side effects, or to the contrary, too short to be symptomatic during
their travel. Indeed, some of the destinations were free frommalaria. Out of the 27 Mefloquine administered clients, 7(26%) showed side effects such as headache, vertigo andnausea, but 17 (63%) did not. Great diversity of malaria
risks regarding the various travel plans of Japanese travelers
makes it very difficult to administer appropriate chemoprophylaxis to the clients. The Guidelines were proved to be
useful for the advice, but further practice and experiences inmalaria chemoprophylaxis were still needed for the doctors
to perform more reliable pre-travel consultation.