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Jpn J Trop Med Hyg Vol 21 No 1 1993, pp. I ‑ 3

1

Editorial

Present Situation and Future Prospects of Tropical Medicine
in Developed Countries
During the past decade international relationships
have been strained by a variety of problems, not only

through medical cooperation, both in Japan and abroad.

diplomatic and economic but also ethnical and religious.

endeavors of the institute have been promoted by its

The field of tropical medicine is no exception. There
are overwhelming and vitally important health problems

domestic and international research colleagues inin tropical areas located for the most part in developing

There are a lot of topics and problems concerning
institutions of tropical medicine. Some of them werecountries. It is essential that the relevant institutions in

Looking back over the history of the past fifty years, therelated academic fields.

European and American countries, whose history ofsome one hundred years is marked by distinguisheddiscussed at the meeting.

achievements in the protection of human health in thetropics, give a thought to what is going on and what isnecessary in the field of modern tropical medicine. The
health of the developing world should always be in the‑Principal function: The principal function of the insti‑

consciousness of the developed industrialised countries.

The symposiurn, entitled "Present situation andfuture prospects of institutions of tropical medicine inadvanced countries", was held in November, 1992, aspart of the activities to celebrate the 50th anniversary of

the Institute of tropical Medicine, Nagasaki University(Nagasaki Institute) (1992) . The symposium was orga‑

nized by the Nagasaki Institute and the Japanese Soci‑ety of Tropical Medicine, and supported by the Ministryof Education, Science and Culture, Government oftution is the sponsorship and organization of researchand education on tropical medicine. Additional func‑
tions include the dissemination and exchange of infor‑

mation, the promotion of cooperation among institu‑
tions and other appropriate scientific activities.

‑Organization and infrastructure: The organization andinfrastructure may differ from institute to institutedepending upon respective circumstances. Some insti‑

tutes operate field stations in the tropics where
epidemiologic, patient‑oriented and laboratory investi‑
gations are being conducted. There is always a need forpatient care, with the mission to diaguose and treat1992) , John E. Fogarty International Center, NlH, Beth‑esda (1992) , Tulane University School of Public Healthpatients with infectious tropical diseases. In addition
there should be the clinical division with beds and an
ambulatory facility for patient studies and care. Collab‑
oration with local hospitals in the tropics is important.
There is often a shortage of staff of intermediate level
as medical doctors and practicing nurses. It is difficult
to find young staff members, especially physicians, as
research fields are too specialized and of limited impor‑tance in industrialized countries. Medical research inand Tropical Medicine, New Orleans, TDR, WHO,developing countries still lags behind because of the lack

Geneva (1990, 1991) , and International Health Institute,Case Western Reserve University, Cleveland. Theof means, and of research staff and technicians.
The Nagasaki Institute is affiliated with Nagasaki

annual and research reports of the London School ofHygiene and Tropical Medicine, London (1990‑91, 1991)

budget. But the staff limitations in small laboratories

were sent to the organizers.

and the necessity of going abroad often disturb theJapan. Participating institutions were Bernhard Nocht

Institute for Tropical Medicine, Hamburg (1990),
Prince Leopold Institute of Tropical Medicine, Antwer‑pen (1990‑1991) , Liverpool School of Tropical Medicine,

Liverpool (1990‑91, 1991‑92), National Institute ofAllergy and Infectious Diseases, NIH, Bethesda (1988,

The Nagasaki Institute is the only government

University and is under government control by annual

Japan. During the fifty years since its inauguration, thecontinuity of laboratory research.
‑Research activities: The expanded definition of tropi‑
cal medicine and recent scientific advances in the field

collaboration institute in the field of tropical medicine ininstitute has devoted itself to research and education inhave resulted in a broadening of basic scientific policies

the field of endemic and tropical medicine and to theand research programs, and in a demand for the partici‑

exchange of scientific and technological knowledge

pation of molecular biologists and modern laboratory

2

techniques. Emphasis is placed on disease‑oriented
basic research; disease mechanisms, pathogenicity of
infectious agents, immune response of the host, host‑parasite relationships, vaccine development, etc. To
this purpose, a section for molecular biology should beestablished through which the technologies of molecular

genetics, immunology and protein chemistry should be
introduced. There is a need for a continuing, active
infrastructure for the organization of basic sciences, notto mention a well‑defined method for the co‑ordinationand exchange of information.
Attention must also be paid to the enhancement offieldwork and health care activities: for example,
epidemiology, methodology of protection of various
kinds of tropical diseases, environmental physiology,
geographical and ethnological pathology, comparative
studies on diseases between the tropics and the temper‑
ate areas, and interdisciplinary research on the relation‑

ships among environmental factors, human ecology anddisease manifestations. The full impact of healthrelated factors can be examined only through commu‑
nity studies.

programs are necessary. They constitute the main
research effort in which major personnel and finacial
resources are tied up. The collaboration at the level ofthe universities should be within the scope of the insti‑

tute. The aim should be to achieve a critical mass oftalent in these programs to assure productivity andsuccess. Widely expanding international collaborations
are important.

‑Budget and research funds: Research funding is an
important matter. Appropriate official funding for
reseatch activities in tropical countries is necessary.
Funding should be reserved for development activities
abroard or for research activities in the country itself.

Each research scientist should have the opportunity toreceive research funding from all areas of society, bothpublic and private. The annual budget for the manage‑
ment of the Nagasaki Institute is provided by the gov‑
ernment through the university.
‑Laboratory facilities: Laboratory facilities including
special facilities for tropical medicine should be avail‑able on the basis of the budget and research funding.
‑Scope and future policy: One of the responsibilities ofOne must take care not to compete with univer‑

the institution of tropical medicine should be to provide

sities. One works essentially in the field of appliedresearch trying to use the technological progress of
medicine to improve the health of the third world, but
the border with basic research can be hazy.
‑Education, teaching program, training system : Teach‑ing in the field of imported diseases is the task of a
specialized institute. Educational programs should bedesigned so that each academic laboratory achieves its
own objective in the field of expertise. They are; I )lectures and practicals for undergraduate medical stu‑

leadership and direction in the advancement of tropical
medicine and primary health care and to perform otherdents at universities, 2 ) a postgraduate course leading
to Ph. D. or other degrees, 3 ) participation in a train‑

ing courses in tropical medicine for doctors, nurses,
technologists and relevant professionals, and 4 ) medi‑

cal research training courses for researchers fromabroad or in the tropics supported by government or
private organizations.

‑Academic services: In addition to the programs
mentioned above, routine academic services of theNagasaki Institute include laboratory diagnostic exami‑
nation of viral, bacterial, protozoal and parasitic dis‑eases, postmortem examinations and histological diag‑nostic pathology of surgical specimens, and the clinicaltreatment of patients with infectious diseases at Univer‑sity Hospital.

‑Collaboration with other organizations: Considerable

emphasis has been placed on collaboratory work ofmany kinds. Two or more institute‑wide research

appropriate duties as required. The institution should be
responsible for the preparation and up‑dating of infor‑

mation on tropical medicine. An important social con‑tribution is the practical work conducted in tropicalareas according to the social needs and policy of coun‑tries concerned. With regard to the strategy for thedevelopment of modern tropical medicine, it is impor‑tant to; I ) encourage the formation of international
cooperation programs such as activities under the ODA
program, 2 ) establish relationships with internationalorganizations such as WHO, 3 ) facilitate the transfer
of research knowledge, equipment and its application topeople in the tropics and provide help and appropriate
assistance to the developing countries, 4 ) disseminate
information about opportunities for education and train‑
ing in tropical medicine, and 5 ) give advice to relevant

government organizations based upon our knowledge
and experience. We must seek to influence politicians
and the public on the importance and justice of tropical
medicine for those we serve in the developing countries.
As a whole, the Nagasaki Institute is on safe groundin Japan for the time being. However, its survival andfuture will depend on its capacity to adapt to the largely
unforesseable evolution of the next decennial and on its
ability to define clearly its place in research and educa‑Jpn J Trop Med Hyg Vol 21 No 1 1993, pp, I ‑ 3tion not only in the tropical developing countries but
also in economically advanced countries. On the basis of

our commitment to tropical medicine and to interna‑
tional friendship, we intend to continue our collabora‑tion with developing countries and advanced countries.

We hope that the above mentioned symposium will be
the first of many future events in Japan attended byspeakers from institutions of tropical countries in thenear future.

of Tropical Medicine
Nagasaki University
I nstitute

Hideyo Itakura

REFEREN CES
1 ) Bernhard Nocht Institute for Tropical Medicine (1990) :Annual Scientific Report2 ) Institute of Tropical Medicine, Nagasaki University(1992): The Proceedings of International Symposium:
Present Situation and Future Prospects of Institutions of

Tropical Medicine in Advanced Countries (The 50th
Anniversary of The Institute of Tropical Medicine,
Nagasaki University) , Trop. Med., 34(4)3 ) John E. Fogarty International Center, NlH (1992): NlH
Annual Report of International Activities (Fiscal Year
1991)

4 ) Liverpool School of Tropical Medicine (1990‑91):
Annual Report5 ) Liverpool School of Tropical Medicine (1991‑92): Pro‑
spectus6 ) London School of Hygiene and Tropical Medicine (1990‑91) : Annual Report7 ) London School of Hygiene and Tropical Medicine(1991) : Research Report8 ) National Institute of Allergy and Infectious Diseases,
NlH (1988) : The edge of discovery9 ) National Institute of Allergy and Infectious Diseases,
NIH (1992): Profile (Fiscal Year 1991)

10) Prince Leopold Institute of Tropical Medicine (1990‑1991) : Rapport annuelll) TDR‑CTD, WHO (1990): Tropical Diseases
12) TDR, WHO (1991): Tropical Diseases: Progress in
Research, 1989‑1990. 10th Programme Report3

5

J pn. J. Trop. Med. Hyg., Vol. 21, No. 1, 1993, pp. 5 7

A NEW BLACKFLY SPECIES OF MA YACNEPHIAFROM GUATEMALA (DIPTERA= SIMULIIDAE)JOSO. OCHOA A.1 AND HIROYUKI TAKAOKA2*

Received November 18 1992/Accepted December 16 1992

Abstract: A new blackfly species, Mayacnephia tadai sp. nov. was described based on the female, pupal andlarval specimens collected from a seasonal small stream in upland of Guatemala. This species is readily
distinguished from the other known species by the number of pupal gill filaments (six).

Mayacnephia is a small genus of the family

dark brown, bare. Pleural membrane bare. Katepister‑

Simuliidae consisting of 10 species, most of which werereported from central America (Wygodzinsky and Cos‑
car6n, 1973). Recently we collected an additional

num glabrous, in profile as long as high, and bare. Wing
lost. Legs also lost except for all coxae, fore femur andhind basitarsus; hind basitarsus (Fig. 3) nearly parallel‑

species belonging to this genus from an upland stream insided, brown, and with well developed calcipala. Abdo‑

Guatemala which is easily separated from the known

men. Basal scale dark brown with dark and pale hairfringe; dorsal surface of abdomen dark brown, densely
covered with recumbent whitish scale‑like pubescence;
tergites of posterior segments semi‑shiny. Terminalia

Mayacnephia species. This is described as a new species
below. The taxonomic characters and their terminology

used here follow those of Wygodzinsky and Coscar6n(1973) .

DESCRIPTION
Mayacne phia tadai Ochoa and Takaoka, new species

Female. Body length 3.0 mm. Head narrower thanthorax. Frons dark brown, covered densely with whitish
scale‑1ike pubescence; frons (Fig. D narrow with frontal angle 60 degrees. Fronto‑ocular areas (Fig. 1) welldeveloped. Clypeus dark brown, covered densely withwhitish scale‑like pubescence, interspersed with several

dark long hairs. Antenna consisting of 2 + 9 segments,
dark brown; Ist flagellomere elongated, ca. 1.8 x lengthof 2nd flagellomere. Maxillary palp with 3rd segment(Figs. 4 and 5) . Sternal plate of 7th abdominal segment
well developed, Iarge and with numerous hairs. Sternal
plate of 8th segment well developed, widely bare medi‑
ally but with ca. 12 hairs on each side; anterior gonapo‑
physes large, subtriangular, apices rounded, medial bor‑ders approximated, surface with numerous microtrichia
and with 15‑18 setae. Genital fork inverted‑Y shaped,
stem and part of arms heavily sclerotized, and arms
with distinct projection directed anterodorsally. Para‑proct in ventral view slightly shorter than wide, andwith ca. 9 dark hairs; in lateral view paraproct not
produced posteriorly under cercus. Cercus in lateralview semicircular in shape, and with numerous hairs.
Spermatheca large, well sclerotized except small circu‑
lar membraneous area at base of spermathecal duct, and(Fig. 2) of moderate size, subequal to or slightly longer
than 4th segment; sensory vesicle ( Fig. 2 ) oblong, ca.

without internal setae.

0.43 x length of 3rd segment. Maxilla with 9 or 12 inner

Pupa. Body length 4.0 mm. Head and thorax. Integu‑
ment yellowish and moderately covered with minuteteeth and 13 or 14 outer teeth. Mandible with ca. 30

inner teeth and 12 outer ones. Cibarium unarmed.
Thorax. Scutum dark brown, densely covered withrecumbent whitish scale‑like pubescence. Scutellum

tubercles. Head with 2 + 2 frontal and I + I facial tri‑brown covered densely with whitish scale‑1ike pubescen‑ce and with several dark upstanding hairs. Postscutellum

pairs; all filaments shortly stalked, subequal to eachother in length and thickness, diverged widely and eachchomes; thorax with 5 + 5 trichomes, all simple andslender. Gill (Fig. 6) consisting of 6 tubular filaments in

Division of Malaria, Ministry of Health, Guatemara City, Guatemara
2. Division of Medical Zoology, Oita Medical University, Hazama, Oita 879‑55, Japan ( *correspondent author)

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Figure 1‑11 Mayacnephia tadai sp. nov. 1, female head showing narrow frons; 2, 3rd segment of female

maxillary palp showing sensory vesicle inside; 3, basitarsus of female hind leg; 4, female
terminalia in situ (ventral view) showing 8th sternite, anterior gonapophyses, genital fork,

paraproct, cercus and spermatheca; 5, paraproct and cercus in lateral view; 6, pupal gill
filaments (lateral view); 7, terminal hook of pupal 9th abdomen (lateral view); 8, cephalicapotome and cervical sclerites of larval head; 9, ventral surface of larval head capsule showing

hypostomium and shallow postgenal cleft; 10, apical tip of larval hypostomium; Il, apical tipof larval mandible. Scale bars, 0.2 mm for Figs. 1, 3, 8 and 9; 0.5 mm for Figs. 2, 4, 5, 6 and
10; 0.05 mm for Figs. 7 and ll.

7with tapered apex; surface of filaments smooth. Abdo‑men. All terga tuberculate; terga 111 and IV each with
4 + 4 hooks posteriorly; all hooks simple; terga V ‑IX
each with continuous spine‑combs anteriorly; terminal
hooks (Fig. 7) well developed and elongated. All sterna

Distribution. Guatemala.

except last one tuberculate; sterna V I and V 11 divided

Guatemalan onchocerciasis.

Remarks. This new species was named after Dr. Isao
Tada, professor of Kyushu University, Japan, in recogni‑tion of his great contribution of research and control of

longitudinally along middle by membraneous, striate

area; sterna V‑VII with 4+4, 3+3 and 2+2 simple

The number of samples examined was small andhooks, respectively, accompanied by 2 + 2 hooks in pleu‑
ral membranes; 9th segment ventrally and laterally withseveral curved, apically coiled hooks. Cocoon. small,short, slipper‑shaped, rather loosely woven anteriorly,
and covering the pupal abdomen alone.

even the unique female adult specimen reared from thepupa was not in a normal condition, missing the wings
and most parts of legs. Nonetheless, this species was
easily assigned to the genus Mayacnephia, defined by
Wygodzinsky and Coscar6n (1973) , by a combination of

Larva. Body length 6.5 mm. Body color pale yellow.

the diagnostic characters of the pupa and larva, such as
pupal cephalic sclerite with 2 + 2 frontal trichomes andCephalic apotome (Fig. 8) broadest well before poste‑rior border, and almost pale with posteromedian andposterolateral head spots yellow. Cervical sclerites(Fig. 8) small, narrowly fused to upper ends of postoc‑
ciput. Antenna as long as stem of cephalic fans; Iength

tubular gill filaments, and larval hypostomium with 13

ratio of Ist, 2nd and 3rd segment 1.0:0.85:1.1. Cephalicwhich are so similar to one another in the adult and

fan with 36 main rays. Mandible (Fig. 11) with numer‑
ous mandibular serrations. Hypostomium (Figs. 9 and
10) with 13 apical teeth in 3 conspicuous groups, withmedian tooth and corner teeth the largest; Iateral bor‑ders weakly serrated anteriorly; hypostomial setae 4 innurnber, diverging posteriorly from lateral borders.
Postgenal cleft (Fig. 9) small, ca. 3 x length of post‑

larval stages but differ remarkably in the pupal stage.
The female and larva of the present new species also areapical teeth in three groups.
This genus is mainly distributed in central America

extending northerly to Canada and southerly to Ven‑ezuela and contains 10 species (Crosskey, 1988), all ofvery similar to those known species. However, thenumber and shape of the pupal gill filaments easily
separate this species from the others.

From Guatemala, prior to this new species, three

Mayacnephia species, namely M. aguirrei. M. pa‑

genal bridge. Thoracic and abdominal cuticle barechecolunai (de Leon) and M. roblesi (de Leon) , have

except colorless simple setae at base of anal sclerite.
Anal gill lobes simple. Anal sclerite X‑formed, poste‑rior arms ca. 1.8 x as long as anterior arms. Ventral
papillae present. Posterior circlet with ca. 76 rows of up

been known, all of which have the differnt shapes of thepupal gills (Dalmat, 1955) .

to 18 hooklets per row.

Type specimens. Holotype, reared adult female
mounted on glass slide, together with its associatedpupal skin and cocoon, Rio Amates, Guanagazapa,
Escuintla, GUATEMALA, 23. VI. 1986. J.O. Ochoa;
paratypes, I pupa in alcohol and I Iarva on slide, samedata and date as holotype. All these type specimens will

be in due course deposited in the British Museum(Natural History) , in London.

Ecological notes. These pupae and larva were collected

together with M. aguirrei (Dalmat) from twigs in asmall temporary stream (width 50 cm; water discharge
8 Iiters/sec.; altitude ca. 1,000 m above sea leveD.
Female has the well developed, toothed mandibles andmaxillae but its feeding habit is unknown.

LITERATURES CITED
1 ) Crosskey, R.W. (1988) : An annotated checklist of theworld blackflies (Diptera: Simuliidae) , p. 425‑520. In:
Kim, K.C. and Merritt, R.W. (eds) "Black flies", 528 p.
The Pennsylvania State University Press, University

Park2 ) Dalmat, H.T. (1955) : The black flies (Diptera,
Simuliidae) of Guatemala and their role as vectors of
onchocerciasis, Smithsonian Institutions miscellaneous
Collections, 125, 1‑425

3 ) Wygodzinskey, P. and Coscar6n, S. (1973): A review ofthe Mesoamerican and south American black fiies of thetribe Prosimuliini (Simuliinae, Simuliidae) , Bull. Am.
Mus. Natur. Hist., 151, 129‑200

9Jpn. J. Tro p. Med. Hyg., Vol. 21, No. 1, 1993, pp. 9 16

THE EPIDEMIOLOGY AND CONTROL OF MALARIAIN THE PHILIPPINES*
CELESTlNO Y. ASlNAS
Received December 3 1992/Accepted January 14 1993

Abstract: Malaria has always been considered a major public health problem in the Philippines. From 1926‑
1946, malaria was identified as the leading cause of mortality and･morbidity having at least two million caseswith from 10,000 to 20,000 deaths annually (Russel, 1936). The implementation of a nationwide malaria
control/eradication program starting 1953, brought down the level of malaria so that it is no longer amongthe 10 Ieading causes of mortality. At present, it is still the 10th leading cause of morbidity. In 1991, themalaria endemic population is about 12.0 out of the total 64.5 million. It is endemic in 72 out of 75 provinces

in varying endemicity ranging from an Annual Parasite Incidence (APD of 0.62 to 43.8/･1,000 population.
Malaria is hypoendemic along the coastal and plain areas and hyperendemic in the foothills and forest
fringes. There is generally no transmission in cities, urban areas and big centers of population because ofunfavorable breeding condition of the vector. Practically, no transmission is found in areas 3,000 ft above
sea level.

The main mosquito vector, Anopheles favirostris, breeds in slow flowing clear, partly shaded streams.
The secondary vectors are An. Iitoralis, a brackish water breeder; An. balabacencis, which are mostly
confined to forested areas; An. mangyanus, which has the same habitat as the An. favirostris, but thrives
better in forested or heavily veg.et ed areas and An. maculatuslwhich prefer clear flowing mountain streams
exposed to sunlight.

The most common parasite species is Plasmodium falciparum (66%) followed by P. vivax (33%) per
1991 records. P. malariae is rare and P. ovale was reported only once in 1969. The results of 18 years
monitoring of drug resistant P. falciparum to chloroquine varies from 28 to 89% classified as RI with some
RII Ievel. In the years 1982, 1985 and 1987, 100% P. falciparum resistance (RD to amodiaquine have beenrecorded.
The Malaria Control Program objective is to reduce the incidence of malaria to 1/1,000 population by
year 2,000 and prevent its reintroduction to malaria freed areas. The key strategy is to implement effective

vector control measures in areas with API>5/1,000 population complemented by the rational use of
appropriate anti ‑ malaria drugs. In areas with API < 5 / 1,000, intensified case finding and immediate

treatment thru PHC supplemented by an active health information system directed towards personal
protection and prevention from malaria. Following these strategies, the national API was reduced from
14.5/1,000 in 1987 to 7.3/1,000 population ending 1991.

I N TRODUCTION
Malaria has always been considered a major publichealth and socio‑economic problem in the Philippines.
From 1926‑1946, malaria was identified as the leading
cause of mortality and morbidity having at least two
million cases with from 10,000 to 20,000 deaths annually(Russel, 1936) . It has been a deterrent in socio‑eco‑nomic development as it has affected resettlement pro‑grams, roads, and bridge constructions, agriculture
development and forest conservation. Various econo‑

mists estimated that the government's loss due tomalaria ranged from 100 to 750 million persos annually(Ejercito, 1954) , when the dollar‑peso rate was 1:2. The

current exchange rate now is 1:26.

EpIDEMIOLOGY
1 . General epidemiology and distribution
Malaria is widely distributed in the Philippines. At
present, it is endemic in 72 out of 75 provinces withvarying degrees of endemicity ranging from an Annual

Director, Malaria Control Service, Department of Health, the Philippines*Presented at Research Coordination Meeting between Endemic Countries and Non‑Endemic Countries on Important Tropical
Parasitic Diseases, held at Maebashi, Japan, July 1992.

10

Parasite Incidence (APD of 0.62 to 43.8/1,000 popula‑tion. In 1991, the endemic population is 12.0 out of theTable 1 Malaria morbidity and mortality statistics from
1946‑1989 per 100,000 population

total 64.5 million. Malaria is hypoendemic along thecoastal and plain areas and becomes hyperendemic as

Year Po pulation

NumberRate N umber Rate

18 , 434 , 400

184 . 482

lOOO . 7

16 , 783

91 . O1947

16 , 785 , 700

ll9 , 395

635 . 6

12 . 070

64 . 31948

19 . 143 , 800

85 , 732

447 . 8lO . 558

55 . 2

1949

19 , 689 , 800

70 , 283

357 . O8 , 80144 . 71950

20 , 315 , 800

63 , 075

310 . 5

7 , 778

38 . 3

1951

20 , 962 , 800

54 , 142

258 . 37 , 72138 . 8

1952

21 , 628 , 300

54 . 591

252 . 4

7 , 170

33 . 2

1953

22 , 316 . OOO

54 . 119242 . 5

6 , 72030 . 1

1954

23 , 025 , 500

71 , 363

309 . 95 , 236

22 . 7

1955

23 , 747 , 600

79 . 707

335 . 5

3 , 71415 . 6

1956

24 , 513 . OOO

73 , 560

300 . 1

2 , 804

ll.4

1957

25 , 292 , 400

60 . 029

237 . 3

2 , 376

9.4

1958

26 . 096 , 600

71 , 666

274 . 62 , 253

8.6

1959

26 , 926 , 400

61 , 645

228 . 91 , 763

6.6

1960

27 , 792 . OOO

55 , 252

198 . 8

1 , 587

5.7

196 1

28 , 727 , OOO

44 , 546

155 . 1

1 , 373

4.8

first decen‑

1962

29 , 698 , OOO

40 , 342

135 . 81 , 273

4.3

tralization

1963

30 , 709 . OOO

36 , 295

ll8 . 2l , 114

3.6

1964

31 , 270 , OOO

40 , 854

130 . 6

976

3.1

1965

32 , 345 , OOO

28 , 988

89 . 6

1 , 015

3.1

1966

33 , 477 , OOO

33 , 737

100 . 8l , 3734.l

1967

34 , 656 . OOO

31 , 441

90 . 7

1 , 147

3.3

1968

35 , 003 , OOO

28 , 354

79 . O

1 , 061

3.0

1969

37 , 158 . OOO

31 . 756

85 . 5

860

2.3

1970

36 , 849 . OOO

28 , 594

77 . 6

666

1.8

1971

37 , 959 , OOO

25 , 338

66 . 8

547

l.4

1972

39 , 040 , 100

27 . 090

69 . 4

656

l.7

1973

40 , 219 , OOO

31 . 999

76 . 6

845

2.l

1974

41 , 457 , 100

27 . 420

66 . 1

938

2.3

1975

42 , 517 , 300

27 , 077

63 . 7

1 , 018

2.4

1976

43 , 751 , 300

35 , 553

81 . 3

997

2.3

1977

45 , 005 , 300

29 , 955

66 . 6

974

2.2

1978

45 , 528 , 500

35 . 353

77 . 7l . 077

2.4

1979

46 , 580 , 400

31 . 779

68 . 2

1 , 1422.5

1980

48 , 316 , 503

39 , 678

82 . l

1 , 091

2.2

1981

49 , 536 . 022

44 , 118

89 . 1

1 , 071

2.2

1982

50 , 783 , 065

40 , 496

79 . 7

985

l.9

1983

51 , 973 , 651

55 . 019

l05 . 9l , 086

2.1

1984

53 , 192 , 708

107 , 485

202 . 1

923

1.7

1985

54 , 668 , 332

121 , 975

223 . 1

1 , 166

2.1

unstable with tendency to develop into epidemics.
Transmission is more persistent in the difficult forest
fringes because of the presence of tribal moving minor‑
ities and illegal settlers not normally reached by healthservices. Transmission is associated with the abun‑dance of breeding places and density of the principlal
vector, An. favirostris and is perennial with two distinct

peaks, at the beginning and end of the rainy season, andgenerally lower during ,the hot summer months. The
temperature ranging from 20‑34'C is favorable for
perennial transmission of P. vivex and P. falciparum
while rainfall and humidity conditions are ideal forvector breeding and long survival. Although mostprovinces are endemic, there is no transmission in cities,

also no transmission in areas 3,000 ft above sea level.

The provinces of Cebu, Leyte and Catanduanes aremalaria‑free.

2 . Mortality and Morbidity

Malaria was already present among the natives
when Magellan first landed on the islands in 1521
(Russel, 1936) . Since then, it remained a problem.

From 1946 to 1952, the Department of Health hasreported that malaria was the leading cause of morbid‑

ity and the 5th cause of mortality. Due to control/
eradication efforts, morbidity rates went down from
1,000.71100,000 to 100.81100,000 while mortality likewise

dropped from 91.0 to only 4.11100,000 from 1946 to 1966.
In 1989 morbidity rate is at 208/100,000 and mortality

rate is down to 1.6/100,000. At present, malaria is nolonger among the 20 Ieading causes of mortality andonly the lOth leading causes of morbidity (Table 1) .

3 . Entomology: The vectors and its bionomics
So far, 34 species of Anopheles in the Philippines
have been confirmed by local entomologists individuallyor in collaboration with foreign workers.
The primary vector of malaria in the Philippines is

An. favirostris (Ludlow). The secondary vectors are:An. Iitoralis (King) , An. balabacencis (Baisas) , An.
mangganus (Banks) and An. maculatus (Theobald) .
3 . I An. favirostris is widely distributed throughout
the islands compared to the 4 secondary vectors
which are limited in distribution because of
breeding and behavioral characteristics. An.

Mortality1946

one enters the foothills and forest fringes. It is generally

urban areas and big centers of population because ofunfavorable breeding condition of the vector. There is

Morbidity

second decen‑

1986

56 . 004 , 130

124 . 153

221 . 7l , 156

2.1

tralization

1987

57 , 356 , 042

121 , 097

221 . 1

1 , 226

2.1

1988

59 , 721 , 307

ll4 . 679

195 . 3

1 , 176

2.0

1989

60 . 096 . 988

125 . 114

208 . O

986

1.6

From Philippine Health Statistics: 1946‑1989

11favirostris breeds in slow flowing, clear, partly

shaded streams and seepages which abound inrolling foothill areas. It is generally zoophilic. It

has been considered a wild species and is seldomfound resting inside houses. When it enters ahouse it prefers resting on walls and objects
within the 0‑2 ft level from the floor, and aroundcorners with 0‑5 candle power light intensity.

4 . Parasitology and drug resistance problem
The most common parasite species is P. falciparumwith around 66% follow,ed by P. vivax with about 33%
per 1991 records. In the past 30 years, the falciparum/
vivax' ratio varies from 60‑70% in favor of falciparum.
P. malariae is rare and P. ovale is reported only once in

Palawan in 1969.
4. 1 Drug resistance problem

proboscis. An, favirostris is still susceptible to

Resistance to anti‑malaria drugs was first repor‑
ted when a malaria technician stationed in Pal‑
awan in 1968 got malaria and did not respond to

DDT.

two courses of amodiaquine treatment. The

An. favirostris is readily recognized by a golden

flaviscence on the ventral apical half of theoccurence was traced to contract workers retur‑ning from abroad. Three foci of drug resistance3 . 2 An. Iitoralis thrives in brackish.‑ water, Iagoons,rock pools and crevices on coral reefs. This

were subseqently identified: one in Palawan,
another in Aklan, Visayan Island group and thethird was in the Central Luzon. From that timeon, monitoring for drug resistance to malaria
was pursued nationally through both macro andspecies is very well adapted to sea water of highsalinity. An. Iitoralis has been found to be amajor vector in the Sulu Archipelago and thecoastal areas of Western Mindanao. It resem‑
bles An. sundaicus except for the presence 6f the

microtests. The results of 18 years survey by theprehumeral pale spot on the wing. Adults may
be found indoors but prefer to bite outside

Malaria Control Service from 1974 to 1991
(macro and micro in vitro techniques) varies

houses.

from 28 to 89% resistance to chloroquine, mostly
RI and RII Ievels (Table 2). Since 1988 to 1990

3 . 3 An. balabacencis is named after the small islandof Balabac in the southern ti･p of Palawan. It

however, micro in vitro tests reveal a 100%

was thought to be a complex form of An. dirus
but Peyton and Harrison in 1979 confirmed it to
be different and thus retained its name of An.
balabacensis. It breeds in forest rainpools, dug
wells, water in logging roads, tire prints andanimal wallows. It is highly anthropophilic but

sensitivity to chloroquine. From 1982 to 1987,
100% P. falciparum resistance (RD to amodia‑
quine have been recorded. Multi‑drug resistancehas been found in Sulfadoxine‑pyrimethamine.
For the past five years, Mefioquine and Quinine

also feeds on monkeys thereby serving as aremain sensitive (Table 2) .

vector of simian malaria.

3 . 4 An. mangyanus is an indigenous Philippine

4. 2

Micro test kits and incubator productions for
drug resistance monitoring

species named after the Mangyan native tribe of

The Malaria Control Service, Philippines, in

Mindoro. It has the same breeding habitat as

coopperation with WHO/CIDA.i‑s producing Drug Resis‑that of An. favirostris but thrives better in for‑tant Micro Test Kits A and B all:d portable incubator forests or semi‑forested areas. The adult resemble
An. favirostris except for the absence of thefiaviscence on the proboscis and the presence oftwo pale spots on the basal third of the coastal
vein. It is exophilic but tends to be anthro‑
pophilic in the absence of available host prefer‑ence in developed areas.
3 . 5 An. maculatus is exophilic, strongly zoophilic,seldom enters houses and prefers to rest out‑
doors amongst vegetations. It breeds in clear

world distribution. Supplies for these test kits andfiowing mountain streams exposed to sunlightbut not in forested areas. Ejercito et al. (1934) ,found the sporozoites in the salivary gland andsince then subsequent dissections failed to show
its presence.

incubators can be ordered through WHO, Western
Pacific Region, Manila.

CONTROL OF MALARIA
1 . Historical background and program development
Malaria control efforts started in 1926 when a
Malaria Control Section was organized in the Bureau ofHealth. Selective larviciding with Paris Green was
initiated and quinine and plasmochine were used forchemotherapy .
By 1930, naturalistic and mechanical methods wereused such as damming, periodic flushing (automatic
siphons) , e rposure of breeding streams to sunlight,

12

Table 2 In vitro studies on drug resistance, Malaria Control Service/Phili ppines, 1974‑1990
ResposeYear reference

1974‑Shute/Valera

MethodPlace of study

Amodiaquine

Chloroquine

Mef loquine

QuinineSdx/PyrMacro

19/46 (41.3%R)

Central Luzon, Cavite,

Macro

46/166(27. 7% R )Abra, Isabela, Quirino,

MES
1975‑Shute/Valera

Mindoro, Palawan, Rizal

MES

Cagayan, K. Apayao, Central
Luzon, Cavite, Mindoro, Pal‑awan, Sulu, Tawi‑Tawi,
Basilan, N. Cotabato

1976‑Shute/ValeraMacro

68/112(60. 7% R )Cagayan, K. Apayao, Zam‑

MES

bales, N. Ecija, Rizal, Occ.

Mindoro, Palawan, Sulu
1977‑Shute/Valera

78/ll3(69. O% R )Macro

Isabela, Quirino, K. Apayao,

MES

N. Vizcaya, Rizal, Occidental

Mindoro, Palawan, Sulu

1978‑MCS

Macro

61/104 (58 .

7%R)

Isabela, Quirino, Cagayan, N.

Vizcaya, Bulacan, Bataan,
Zambales, Rizal, Occ. Mindor‑o, Aurora. Palawan, Quezon,
Sulu, Tawi‑Tawi, Davao

1979‑MCS

55/90(61. 1% R )Macro

Isabela. Cagayan, Ifugao, Q.C.

Rizal, Cavite, Aurora, Pal‑awan, Quezon, Sulu, S.
Cotabato

1980‑MCS

21/35(60. O%R)

Macro

Isabela. Cagayan, Bulacan,
Bataan, Caloocan City, Rizal,

Or. Mindoro, Palawan, Sulu

198 1‑MCS

41/46(89. l%R)

Macro

0/25 (100% S )Cagayan, Bataan, Rizal,
Laguna, Palawan, Quezon, Or.
Mindoro, Sulu, Basilan

1982‑MCS

22/38 (57 .9%R)

Macro

0/38 (100% S )Rizal, Camarines, Norte,
Agusan Norte, Davao Norte

Sarkovski et al.

Macro(NAMRU)Micro

1983‑MCS

Micro

9/14 (64 .

3%R)

9/9 (100% R )9/42 (21% R )18/31 (58 . l% R )

2/9 (22 .2%R)

Occ. Mindoro

1/31(3. 2%R)

Bulacan, Cagayan, Quezon,
Eastern Samar, Agusan Norte

1984 ‑MCS

Micro

1985‑MCS

Micro

4/4 (100% R )Sarkovsk i

Micro

3/59 (5% R )1986‑MCS

Micro

10/12 (83 . 3% R )Watt, et al.

Micro

4/5 (80% R )1987‑MCS

Micro

17/26 (65 . 3% R )5/13(38. 5% R )

0/4 (100% S )6/11 (54 . 5% R )

0/8 (100% S )Bulacan, Rizal

4/59 (6 . 8% R )San Lazaro Hospital

Rizal, Occ. Mindoro

l0/12(83. 3%R)

0/5 (100% S )

0/5 (100% S )

1%R)

0/3 (lOO% S )0/18 (100% S )Bulacan, N. Ecija,
Bataan. Quezon

Rizal,San Lazaro Hospital
12/21 (57 .

2/7(28 .6%R)

Quirino, Bulacan, Bataan, N.

Ecija, Quezon, Negros
Oriental, Zamboanga
Long et al.

Micro271144 (18 . 7% R )SanofiMicro

8/8 ( 100% R )Micro

12/22(54. 5%R)

0/8 (100% S )

0/8 (100% S )0/15 (lOO% S )0/22 (100% S )RITM Laboratory(MCS/RITM)
1988‑MCS

0/20 (100% S )6/19(31. 6% R )Mindoro, Aurora,

Quezon,Laguna, Bulacan

1989‑MCS

Micro

4/6 (66 . 6% R )

0/6 (100% S )

0/2 (100% S )

0/6 (100% S )

2/5 (40% R )Bulacan, Quezon, Laguna,Bataan, Or. Mindoro,
Cagayan and Caloocan CityMCS/RITM (Halofan

Micro

14/15(93.3%R)

0/15 (100% S )0/28 (100% S )0/15 (lOO% S )0/12 (lOO% S )Micro

5/13(38. 5%R)

0/12 (lOO% S )

0/1 (lOO% S )0/12 (100% S )

0/9 (100% S )trine Clinical Trial)

1990‑MCS

K. Apayao, Bulacan, Palawan

13

slopping stream banks, herb*･ge cover and larvivorous
fish (Ejercito, 1936) . Gambusia affinis was introduced in

Manila by the Americans from Texas. Since that time
onwards scientific studies of the epidemiology ofmalaria, vector bionomics and various control measures
were undertaken. These became the basis for launchinga national malaria control program in 1953.

From 1952‑1954 a DDT Pilot Project in Mindoro
was conducted. After demonstrating that DDT is an

the programs evaluated was the malaria control pro‑gram. Executive order No. 119 dated January 30, 1987
was issued giving opportunities for the new manage‑
ment to reorganize and introduce innovative approaches
to malaria control. Noting the deteriorating endemicity
level of malaria and considering the lessons experienced
from the previous decentralization, the new organiza‑tion was restructured to be semi‑vertical wherein aeffective and economical method of controlling malaria,

strong vector control service was placed directly under
the direction of the Provincial Staff while case finding

WHO and the US government fully backed theand treatment was integrated at the District HealthPhilippines for a nationwide DDT spraying operation.

levels.

The result was quite successful that by 1956, the control

The present MC program is strengthened by a five

objective was changed to an eradication program. In
1959, malaria was dramatically reduced to about 1.2/

Table 3 Parasitological Indices from 1957‑1991

1,000 population that everyone was hopeful that malaria
can be eradicated.
It was unfortunate for the program that in 1959, theYear

Population
at risk

SPR

API

1957

24 . 20

governm6ht started its reorganization. The Department
of Health‑ was required to decentralize the Malaria

1958

2 . 801959

1 . 21

Eradication Service (MES) and placed it under the
direct administrative control of the eight Regional
Health Offices. MES was reorganized and performed

1960

5 . 531961

4 . 531962

6 . 911963

3 . 43

1964

4 . 441965

6 . 65staff functions. The next six years of the program saw
resumption and resurgence of malaria. The objective of
malaria eradication became dim. A,fter a review of the
program and an administrative campaign to centralize

ABER

Remarks

Decentralization

1966

1 . 86

Centralization

1967

3 . 29(RA 4826)

it once more, Republic Act 4826 was passed in 1966.

1968

2 . 23This act mandated a centralized nationwide eradication

1969

1 . 90program under one director with the assistance of1970

3 . 22

1971

11 , 433 . 109

3. 04

3 . 241972

11 , 575 , 121

3. 30

2 . 407 . 10Martial law

1973

11 . 857 , 517

7. 20

6 . 108 . 40(1972‑1981)

1974

11 , 157 , 908

7. 33

7 . 47

10 . 20

around 3/1,000 population. With the phasing out of
USAID and WHO beginning 1973 and the diminishing1975

12 . 028 , 879

6. 40

5 . 809 . 101976

13 , 914 , 846

5. 40

5 . 209 . 4010gistics support of the government, API went up toaround 6/1,000 and maintained at that level until MES
was again decentralized and integrated to the Field
Health Services through Executive Order No 851 in
1983. The problem of inadequate resources remained,

1977

14 . 298 , 709

7. 80

6 . OO7 . 701978

14 , 441 , 556

10. 407 ̲ 306 . 901979

14 , 631 , 273

8. 60

5 . 906 . 801 98 O

15 , 813 . 846

ll. 606 . 606 . OO

1981

14 , OOO , OOO

12 . 30

5 . 804 . 801982

16 . 297 , 226

lO . 70

5 . 905 . 5012. 505 . 904 . 80USAID and WHO. Twenty American Peace Corp
Volunteers were also assigned with the Program.
Annual Parasite Incidence (APD was maintained at

vector control was limited to containing fiare‑ups and

10 . 70

integration (EO 851)

1983

15 , 142 , 521

house spraying was selective and partial. Only bed‑rooms were sprayed. Malaria situation worsen and API

1984

15 . 483 , 321

15 . 106 . 904 . 601985

11 . 111 , 366

23 . 50

9 . 203 . 90steadily rose to about 7.8/1,000 by the end of 1986. In
1987 API dramatically went up to 14.5/1,000 population

1986

13 , 128 . 205

16. 507 . 804 . 70People power revol

1987

10 , 587 . 598

16 . 70

14 . 50lO . 50

MCS strengthened

1988

11 . 126 , 133

ll. 4013 . 90

12 . Ol(EO 119)1989

11 . 666 , 219

7. 50

9 . 9012 . 70

1990

11 , 348 , 235

7. 30

7 . 3010 . OO

1991

ll . 871 , 273

6. 81

7 . 2810 . 68(Table 3, Fig. 3) .

2 . Current status of the program:
After the famous bloodless people power revolutionof 1986, major changes in the organization and manage‑

ment were introduced by the new DOH Ieaders. Among

From Anmual Reports, MCS: 1957‑1991

WB assistance

14

year

loan

from

the

World

Bank

which

took

effect

such

July，

as

GeneralAppropriation

Aごt，W6rld

Bank，

AreaDevelopmentProjects，WHO，USAID，NGO，

1990．

2．1

0bjective

etc．；

The

malaria

generalobjective

incidenceisthereduction

to1／1，000populationby（6）Staffofyear

Policiesandstrategies

The

programadopted

the

by

World

Healthadvocated
1978inofthemalaria

tion

of

now

moving

4th

the

of

PHC，namely：reductionmortality

andmorbiditytoprevalencetheinitialandkeystrategy

controlmeasures1，000population

is

to

in

implement

areascomplemented

appropriate

withAPI＜5／1，000，intensified

immediateedananti−malaria

treatment
activetowards

from（9）Fielding

is

tion

the

through

healthpersonalmalaria．

rational

case

information

some

the

cial

levels；（2）Setting

aside

at

direct・preventionof（2）Emphasis

provin−HealthOmces；
andmalaria

coordinators

atmunicipal

healthfromdifferent

funding〉10／1，000API

The

sources

use

use

shall

be
the

of

exam．

invest．

ment

一

一

》

》

＜7／1，000ヅ

0ptiona1

Optio−（PCDonly）

Figurel》＜7／1，000

一

Malaria

control

初

areas

and

application

measuresperstratified

in

case

areas

finding

parallelandofwith・AIP正＞andControl

of

the

of

staggered

by

drugs

types

area

early

development

mosquito

vector（s）；

andofcontrolChemi−

dial

cal

gical

（Clinical
only）

strategieininconsideringofbyinsecticides

interval

insecticidetoresis・

mosquito

MeasuresReme−》volun−

partiCipation

treatment；

different

Treat

》

immedi・development

Communityanti−malaria

Biolo−

ゾ

nal

and

Vector

Blood

》

for

WHO／CIDA

Strain；prevent
tance

ACD／
PCD

》

incubator（6）Supplementary use of impregnatednet as＆control measure；levels；

Epid．

》

and

with

control

involving

Surveillance〈1／1，000services；international

different

一

Focal
l

cycle

spray
2cyclespray
stratined

Personal

Environ−menta1

一

一

Selec−

Selec−

tive

tive

》

》

》

》

areas

Protec−

IEC

tion

︾︾︾︾

5−10／1，000API

collection

（5）

field

regional，

andto丘eldand一︾︾ヅ

＜5／1，000API

blood

︾﹀ 一一

freed

poSt

reSiStant

Vig．

kits

endemic

vectortreatment（4）Rational

planningGO

coordination

control

tary

by

Mod．

test

of

ate

and

Malaria

Malariaonspraymen

fmds

NGO，

insecticides，drugs，

5／1，000

allowancesonevalua・

distribution．

appropriate

travelStratification
API／1，000

world

hiringguidelinesandarea（Fig．1）

areas，when

andresistant

Strategies；

forprovincial，district（5）Securing

in

for

operations；

of

of

their

Regional／Provincial（4）Creation

Production

funds

respectiveofto∂伽researchpayingandIssuance

Linkages（1）Stratification

regional

canvassers（3）

of

supportand（3〉Intensified／stratified

organization

monitoring

logisticalandparticipation．

Standard

o伍ce

procurement（12）a）Policies（1）

drugs；

parasiteequipment

systemandwithtestingagencies；

apPropriate，biological−enviro㎜ental manage−
ment measures are implemented thro廿gh com−munitycentralb）selectedof（10）Centralizedareasfinding

continuedanti−malaria

monitoring

supplement−

PHC

protection

In

API＞5／

drugs．Inandcollaborationandteams；（11）

effective

with

by

of

by

of

insecticides

ininstitutions

strain；reduc−

incidence．It

implementation

use

ed

and

of

research

research（8）Continued

invariant．

The

vectorvariants

Assembly

context

malariatacticalothertacticaloftechnol・ogy；（7）Operational

2000．

2．2

development，training，transfer

15

1 5.0
O̲

<

1 2.5

8

As of Dec.1 991
1 0.0

7.5

Q)

cU

5.0

O!
CU

2.5
0.0

1987 1988 1989 1990 1991 1992 1993 1994 1995
Year,

Actual Planned
LJ

Figure 2 Planned and actual'API reduction Malaria Control Service, 1987‑1995.

25

API (Per Thousand Population)

Ma la ria Era d lo tloh

I

L

Con trollCentr lized

O̲

<

ll

Centralized

Decentralized

20

i

i

P̲]

(:)

o

E.O. 1 19

Martial Law

,

(D

D

o

:o
COCTS

15
WHO/USAID Fund Terminated10

E.0.85 1

t

l‑clS

O̲
CU

5

o
1 960

1 9651 970
1 975
1 980
Year

1 985

1 990

Figure 3 Annual parasite incidence, Philippines, 1957‑1991.

(7) Establishment of integrated microscopy centerat district level: Clinical diagnosis is advocated in

3 . Accomplishments
The national Annual Parasite Incidence (APD has

highly endemic areas and where appropriate;

been reduced from 14.5/1,000 in 1987 to 7.3/1,000 popula‑(8) Intensification of IEC/health informations;tion ending 1991. There are twenty‑one provinces whichhave attained an API Iess than 1/1,000 population and(9) Scheduled monitoring and evaluation

16

three non‑endemic out of 75 provinces as of 1991. It isprojected that by 1994, the average API will be aroundthe Philippines
4 ) Ejercito et al. (1954): The six‑year Philippine Malaria

2.5/1,000 population (Fig. 2) .

Control Program, Amer. J. Trop. Med. Hyg., 35 ) Five‑year directional plan, Malaria Control Service
Department of Health, 1989‑1993
6 ) Salazar, N.P. (1989): The malaria situation in the

3 . I Comparative accomplishments: 1987‑1991
Particular1987 19881989 1990 1991

1. API

14 . 5

13 . 99.9

7.3

7 . 28

2. SPR

10 . 5

11 . 4

7.8

7.3

6.81

3 . ABER

13 . 812 . 1

12 . 7

10 . O

10 . 68

4 . Smear exam, l ,113,784 1, 356 , 024

1 , 478 , 968 1 , 183 , 370 l , 268 , 284

5 . Positives

154 , 091

154 , 943

115 , 542

86 , 17286 , 392‑ P, faici rum

104 , 281

107 , 373

76 , 730

52 , 781

56 , 867‑P. vivax

48 , 285

46 , 779

38 , 079

32 , 983

28 , 778‑Mix inf tioDS

1 , 525

79 1

733

408

747

270 , 729

651 , 04 1

686 , 539

671 624

662 , 004

6 . Housess ra ed

4 . Problems/Constraints
4 . I Administrative(a) Untimely/delayed release of funds; funds still
inadequate;(b) Lack of trained malaria personnel. No takers,

salary being not commensurate with difiicult
tasks;(c) Malaria is presently a low priority program by

RHO/PHO. Malaria is now the 10th leading
cause of morbidity and no longer among Ist 20
cause of mortality.

4. 2 Technical(a) Parasite resistance to some anti‑malaria drugs

4. 3 Operational(a) Refusals to house spraying with DDT;(b) Population movement;(c) Lack of transport facilities;(d) Incomplete treatment of cases due to attitudeof patients;(e) Apathy of community in participating in thecontrol program;(f) Uncertain peace and order condition in manyhighly endemic areas.

REFERENCES
1 ) Annual Reports, Malaria Control Service, 1954 to 1991

2 ) Asinas, C.Y. (1991): Current status of malaria andcontrol activities in the Philippines, 1991. Presented

during; Technical Meeting on Advanced Knowledge on

Malaria in Southeast Asia, Nov. 1991 Bangkok,
Thailand3 ) A {special report to the secretary of health, Philippines(1961) : The current status of the malaria eradication in

Philippines: A critique: State of the Art‑Malaria
Philippine Council on Health Research and Develop‑
ment, 1‑49
7 ) Sambasivan, G., Santos, M.N. eo al., (1954): Mindoro
DDT Pilot Project. Final report submitted to WHO8 ) Santos, M.N. (1988); Malaria control program: Man‑
agement and research needs. Proceedings of the Third
National Congress on Health Research and. )evelop‑
ment, Philippines, 92‑106

9 ) Payne, David, Evaluation Report of in vitro, in vivo
surveillance in the Philippines, 1986

Jpn J Trop Med Hyg Vol 21 No 1 1993, pp, 17‑19

l 7

NEUROPATHOLOGICAL OBSERVATION OFFUNGUS DISEASES IN THE TROPICSSHIRO NAOEi, KAZUTOSHI SHIBUYA1,MEGUMI WAKAYAMAI AND KATSUHISA UcHIDA2
Among about 100,000 species of fungus, it is said
that pathogenic fungi are about 100 species.
In deep‑seated fungus diseases, there are primary
mycosis and secondary mycosis. Secondary mycosis isvery common throughout the world as an opportunistic
infection. However, as for primary mycosis, fewercases are seen and mostly endemic. It is particulary
significant in the tropics, but very rare in Japan except

chromomycosis and a few cases of cryptococcosis.

MATERIALS AND METHODSIn mucormycosis, hemorrhagic infarction is often
observed, whereas granuloma is rare.
Nocardiosis is mainly caused by Nocardia steroides
which produces abscesses in lung and brain. The disease
currently occurs on the immunocompromized host afterorgan transplantation. Delicate filaments are present(Fig. 3) .

As a typical primary fungus disease, histoplamosis
is endemic in some regions of USA along the Ohio andMississippi River, but cases have also been reported
from Central and South America, Africa and very rarely
from Indone8ia. Clinical signs resemble closely to

Cases with cerebrai lesions were used among mate‑rials hitherto gathered. Most of cases of tropicalmycoses were from institutions of foreign countries.

PATHOLOGICAL CHANGE
OF OppORTUNISTIC FUNGUS DISEASEAs an opportunistic infection> candidiasis is spread‑ing hematogenously with many diseases including SLE
as primary disease. There are numerous spotty hemor‑rhage and lesions are also present in the ventricle. In thecase like this, fungal elements of Candida stretch,morphologically simulating to true filamentous fungi,
with tissue reaction being very rare.

In aspergillosis, Iesions resemble to those by Can‑

Figure ldida, but hemorrhagic focus of Aspergillus is rather
larger. Histologically, emboiic lesions are present.

In cryptococcosis, granulomatous primary focus issometimes found in lung, and when the host falls into theimmunosuppresive condition, systemic cryptococcosis
becomes present through hematogenous spread. It isevident that there are many fundamental diseases whichbring about the decreasing of cellular immunity. It isalso characteristic that multiple cystic lesions are devel‑̲*i * ;*i.
;

oped (Fig. l). Histologically, it is meningoencephlitic
lesion without tissue response (Fig. 2) .

. j

!!:

::i

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t #, ; : ,;;FS .

#/+'*i.;{. {Figure 2

1 . Department of Pathology, Ohashi Hospital. Toho University School of Medicine, Tokyo 153, Japan.
2 . Research Center for Medical Mycology, Teikyo University School of Medicine, Tokyo 193‑03, Japan.
Presented at Xlth International Congress of Neuropathology. Kyoto, September, 1990.
Thi8 manuscript (special article) is reproduced with author's permission.

*. '..
1;:;i;:;: ;.*･f ,･,;,; :.

;:･･

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';;" +=<= i **=.,,*.'.} = <****'> :** "*Figure 4

Figure 3

tuberculosis. Involvement of the brain in this disease iscrophage (HAM) .

uncommon, however when involved, there appeares

Coccidioidomycosis is typical primary mycosis dueto the fungus, Coccidioides immitis, which has the mostinfectious pathogenesis. The disease has a distribution

meningitis type with meningoencephalitic feature orabscess formation including yeast cells. Although veryrare in case, epithelioid cell granuloma with caseous
necrosis closely mimic to tuberculosis is developed.
Fungal elements of Histoplasma capusulatum are seen in
the central zone of caseous necrosis, which were stainedusing anti‑Histoplasma capusulatum antibody made byourselves.

in Western parts of USA, Mexico and the Pacific sidefrom the Andes of South America, but more particularly
in San Joaquim Valley of California and Arizona ofUSA. Lung, spleen and brain are frequently involved.
Dr. Hungtington reported that the cerebral lesions wereseen in 82 cases among 142 autopsy cases (58%). In the
CNS, the disease can present as a meningitis and menin‑

GENERAL PATHOLOGICAL ASPECT IN TROPICS

goencephalitis (Fig. 5), and the formation of
granulomas is often observed. Fungi occur in tissue as

African histoplasmosis and Lobo's disease are lesssac fungi containing endospores. Meningeal and sub=common and no cases with lesions of Central Nervous
System (CNS) have been reported.
North American blastomycosis is endemic in USA

meningeal glias are proiiferated, and within theand Canada, but it has also been reported in Venezuela,
Congo and South Africa. CNS is involved in the ratio of

cidioidomycosis, glias proliferate around the granuloma

3‑20% and the lesion presents as the combination of
suppurative and granulomatous reaction. Meninges,

GFAP･PAS and HAM.

inflammatory change of the meninges, macrophages by
HAM are increasing. In granulomatous type of coc‑

and a lot of macrophages are seen in granuloma by
As to rhinosporidiosis, two cases have been report‑

basal ganglia, cerebellum and spinal cord are known to
be involved.

South American blastomycosis, synonym for par‑acoccidioidomycosis, is mainly observed in Latin Amer‑ican countries. Lesions are mainly seen in lung, Iymphnode, adrenals and liver. Incidence of lesiohs in the CNS

is about 10%. Cerebral involvement pres nts as
granulomataus lesion and there are two forms; meningi‑
tis and granuloma (Fig. 4). Yeasts lO‑60 pm in diame‑ter with multiple buds are seen in the granulomatous
lesion. In meningitic forms, the lesion tends to be mainly

10calized on the base of the brain. Cells positive to

GFAP proliferate around the abscess. Around fungus'> i"* *'<;"･,:*;," i"'""

agent positive to PAS reaction, there appeared numer‑

ous macrophages stained by anti‑Human alveolar ma‑

Figure 5i "^i'=;; ･:": ;:1 {･':;:･;(i･=,= ***{*"

19

ed with the involvement of spinal cord, however, nocases with the lesion in the CNS.
Cladosporiosis in the CNS is a general term for theidiseases caused by brown fungi, socalled Dematiacea
such as genus of Cladosporium. Phialophora. Foncecaea.
Exophiala. However, the name is usually restricted tothose only by Cladosporium spp, such as C, trichoides. C.

bantiarum. C. gougeroti. C, carionii. When using the
restrictive name, the diseases by the other brown fungi

are called to be chromoblastornycasis or
chromomycosis. Many cases have been reported inEurope, North and South America, Africa, Indonesia,
Taiwan, Japan, etc.

Figure 7

In tropics, there are many cases of diseases bybrown fungi. However, in Japan, there are a few cases
by Cladosporium spp., while as to chromomycosis, about

Observing periodic change of the lesions, we studied thecourse to produce granuloma (Fig. 7) .

20 autopsy cases are reported, most of wihch are of

Lesions may occur in any part of the brain. In somechildren under 15 years old. It is also characteristic thatcases, meningitis was developed, but in most cases,
abscess with fungal elements was produced.
On the 7th day after injection, prominent glioses
were present. On the 17th day, appearance of macro‑phages became marked, and there was a tendency to
produce granulomas.

cerebral involvement is present in many cases (Fig. 6).
In chromomycosis, it is characteristic that brownish

black lesions are present. Generally, granulomatous
lesions are developed, and the meningitic lesions areoften seen with the involvement in VirchowRobin's
space. Multinucleated giant cells are phagocyting fun‑gus with the proliferation of glias around. Iviacrophages

are also increased. In only one case, within the severe
inflammatory cell infiltration, numerous B‑cells wereobserved, but no T‑cells.

SUMMARY
The cerebral iesions of fungus diseases are of three

types; meningitis type, encephalitis type and mixed typeof the both. As to infiammatory changes, the translation

The formation of multiple granulomas are thought
to be by means of hematogenous spread. However, infrom suppurative inflammation to granuloma was obser‑

human cases, as the formation of lesions and their earlyved.

stage cannot be observed, we carried out the experimentusing mice.
Mice were intraveneously injected with 2 strains ofhost by prominent proliferation of fungi following bacte‑rial bashing induced by antibiotics. It is usual that there

Exophiala dermatit･idis demonstrating different virulence

is no tissue response.

Secondary mycosis arises in immunocompromized

which were isolated from human brain and lymph node.

ACKN OWLEDGEMEN T
The authors greatefully acknowledge Prof. Hideyo

Yamaguchi, Research Center for Medical Mycology,
Teikyo University School of Medicine, for his helpful
suggestions and comments during the preparation of thismanuscript.

REFEREN CESl ) Baker, R.D. (ed) . (1971): The pathologic anatomy of

mycoses. Human infection with fungi actinomycetes
and algae. Springer‑Verlag. Berlin2 ) Naoe, S. et al. (1984) : Fungus disease and related

Figure 6diseascs in tropics, Byori to Rinsho, 2, 1198‑1207

Jpn. J. Trop. Med. Hyg

Vol 21 No 1 1993, pp. 21‑24

21

ALTERATIONS OF SPINAL CORD IN
JAPANESE B ENCEPHALITISMASAO KISHIKAWA
Abstract: The cytopathologic changes of Japanese B encephalitis (JBE) are basically similar to those ofother forms of arbovirus encephalitis. Because the entire central nervous system including the spinal cord

is involved to varying degrees, the nomenclature of JBE should actually be Japanese B panence‑phalomyelitis.

five aged patients who underwent autopsies (Table 1).
The duration to death was 4 days to 307 days. All ofJapanese B encephalitis (JBE) is a tropical neuro‑ these JBE cases were confirmed serologically. Neuro‑
10gical disease found in the countries of east and south pathological investigations were performed histopath‑Asia, such as Japan, Korea, China, Taiwan, Malaysia, ologically and immunohistopathologically.
Indonesia, Thailand, Nepal and India. Since the isola‑tion of the pathogenic virus by a Japanese neuropsy‑

INTRODUCTIONRESULTSchiatrist in 1934, the disease has been called Japanese B

encephalitis (Hayashi, 1937) . As a result of the geo‑

The surfaces of the brains usually showed conges‑

graphical distribution, very few neuropathological tive and sometimes edematous changes. But no suppur‑
details of JBE can be found in European and American ative alterations were observed. The thalamus, corpus
textbooks. Descriptions of the spinal cord lesions are striatum and substantia nigra were always affectedalso rare in the textbooks.
prominently. Hemorrhagic lesions were frequently
found in the thalamus. Petechiae and small foci of

MATERIALS AND METHODS necrosis were also detected not only in the thalamus but
also in other parts of the cortex and centrum semiovale.

Spinal cord and brain specimens of nine JBE cases Histologically, focal and small necroses of the cerebral
were available from two children, two middle‑aged and cortex were frequently observed. Vacuolar changes ofTable I The cases of spinal cord studies on Japanese B encephalitis

N o. Age
4 mos.
2

5 yrs.

3

47

4

51

5

65

6

65

7

69

8

72

9

82

Sex Antibody

M
M
M
F

M
F

M
M
M

Duration

Ttt
tt
tt
tt
tt
tt
tt
t

4 daysBrain

Others935 g

Brain edema
Brain edema

8

1, 30018

1370Only spinal cord

307
14

1, 25068

1, 1404

1

18

1, 36012

1, 100

Cervical cord

300

Brain edema

Duration: course from onset to death (days)

Department of Pathology, Scientific Data Center for the Atomic Bomb Disaster, Nagasaki University School of Medicine, 1‑12‑4

Sakamoto, Nagasaki 852, Japan.

A part of this paper was presented at Xlth International Congress of Neuropathology. Kyoto, September, 1990.
This manuscript (special article) is reproduced with author's permission.

22

reactions such as glial nodules and neuronophagia (Fig.
lb) , petechiae and myelin loss were detected. Of all thethe cerebral cortex and white matter were also occa‑
sionally found. Glial nodules were one of the mostconspicuous alterations. The reactive cells werespinal levels, the lumbar portion was affected mostastrocytes and microglias. Neutrophils were also mixed
in the glial nodules in the cases lasting only 4 days.
Perivascular lymphoid cell cufling was easily detected.
Relatively well circumscribed demyelinated lesions werealso commonly observed. The axons of these foci werealmast completely preserved. Cases of long duration,
however, showed a few axonal swellings. Immunohist0=
chemical staining for antiJBE virus antibody (courtesyof Dr. Sata. JNIH: Tokyo) showed positive findings in
the neurons of the thalamus (Fig. Ia) . The substantia

severely. Neuronal loss of the anterior horn and rare=faction were detected occasionally. Perivascularlymphoid cell cufiing was clearly evident, while thicken‑

ing of the vascular wali was not observed in JBE.
Central chromatolysis was found frequently in the
motor neurons of the anterior horn. Three of the ninecases showed some degree of alterations in the lateralpyramidal tract, but with indistinct circumsription.

Two cases showed mild demyelination and/or myelin
pallor (Fig. 2a) , and the other case showed moderatevacuolar changes in the pyramidal tract. The pyramidal
lesion was more prominent at the thoracic level. The

nigra was another ane of the most severely affectedsites. Marked gliosis and neuronal degeneration withdropping out of neuromelanin were easily observed.
Although the entire cortex was involved mildly toseverely, the thalamus, midbrain and corpus striatum
were mainly and severely affected in all cases. The

cerebellum, pons and medulla oblongata were alsopatient who died after oniy four hospital days also
showed vacuolar changes in lateral pyramidal tract. A
few cases showed intracytoplasmic vacuolar changes in
the large neurons of the anterior horn. There was no
confirmation of the existence of neutral fat in these

involved to varying degrees.

vacuolar lesions. Perivascular lyinphoid cell cuffing andWith regard to the spinal cord, macroscopically,
moderate to marked congestion was found in almost all

chronic inffammatory cell infiltration were also observed

JBE spinal cords. Microscopically, the spinal lesions of
JBE displayed basically the same appearance as those inequina. Demyelinating foci were occasionally detectedin both the motor and sensory nerves of the cauda
in the peripheral nerves (Fig. 2b) .

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23;

Mild demyelination and/or myelin pallor is seen at

Figure 2 a. Alteration af the lateral pyramidal tract

the lateral pyra lidal tract ( * ) of case No. 7. KB stain, >< 30. b. Sensory nerve of the cauda

equina of case No. 5. Dernyelinating lesion (1eft side) and preservation of myelin (right side) are

mixed. KB stain, x 150.

be found in European and American textbooks. Before
discussing the neuropathological features, it will be

DISCUSSION

As a result of the geographical distribution of theuseful to present a brief epidemiological introduction of

disease, very few neuropathological details of JBE can

JBE in Japan.

xlaX}

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Figure 3 The number of cases of Japanese B encephalitis in Japan: 1948‑1988.

24

JBE has been the subject of a nation‑wide statisti‑

cal surveillance in Japan since 1946 and has been
designated as a legal epidemic disease since 1954. The
number of cases peaked in 1950, with 5,196 patients anda morbidity of 6.2. From 1948 to 1967, more than one‑thousand patients were detected each year. In recent
years, however, a total of less than 50 patients (Fig. '3)

and 0.0 morbidity are observed. JBE was seen predomi‑
nantly in children and in aged groups. But in recent

years, very few cases are detected among children
because of vaccinations for JBE. The southwestern partof Japan, especially the island Kyushu, shows the highest

incidence, while most of the northern island Hokkaido,
located above a latitude of 41'N, has no JBE patients.

The morphological aspects of JBE are basicallysimilar to those of other forms of arbovirus encephalitis,

with the exception of Eastern equine encephalitis(Heffner, 1976). Macroscopically, brain edema andcongestive changes are the most prominent features inthe early phase. Although the infiammatory reactive
cells are mainly neutrophils rather than lymphoid cells
in Eastern equine encephalitis, the reactive cells of otherforms of arbovirus encephalitis including JBE are main‑
ly lymphocytes and glial cells (Heffner, 1976) .
Very few details of the spinal changes can be foundin the English literature. The spinal changes of JBE
display basically the same features as those of otherforms of arbovirus encephalitis, such as glial nodule,
neuronophagia (Fig. Ib) , petechiae and myelin loss.
Perivascular lymphoid cell cuffing is also prominent,
while thickening of the vascular wall such as that seen

in HTLV‑1 associated myelopathy (HAM/TSP) (Ak‑izuki et al., 1989) is not observed in the spinal cord of
JBE. Mild demyelination and/or myelin pallor (Fig. 2a)and moderate vacuolar alterations in the lateral pyrami‑
dal tract were detected in three cases in this spinal
study. Some aspects of the alterations in the lateralpyramidal tract, which show indistinct circumscriptionof the lesion, might be secondary to proximal lesions
such as those in the cerebral cortex and white matter.
In the acute phase, however, edematous changes mightplay the role of vacuolar changes, because one case withlesions in the lateral pyramidal tract did not show
lesions in the related cerebral areas and this patient diedafter only four hospital days.

Because the entire central nervous system including

the spinal cord is involved to varying degrees, thenomenclature of JBE should actually be Japanese B
panencephalomyelitis.

ACKNOWLEDGEMENTS
The author expresses his appreciation to Dr. S. Era(National Beppu HospitaD , Dr. Y. Otsuka (Kumamoto
Chuo HospitaD , Dr. H. Miyayama (Kumamoto Munici‑
pal HospitaD , Dr. M. Takeya (Kumamoto University) ,Dr. O. Nakashima (Kurume University) , Dr. H. Fujii(National Nagasaki Chuo HospitaD , who provided thespecimens of JBE. Thanks are also extended to Dr. T.
Sata (National Institute of Health, Japan) for his im‑
munohistochemical staining with anti‑JBE virus anti‑
body.

REFERENCES
1 ) Akizuki, A., Yoshida, S., Setoguchi, M. et al. (1989):

The neuropathology of human T‑lymphotropic virus
type‑1‑associated myelopathy. In Roman G.C., Vernant
J.C., Osame, M. (eds.), HTLV‑ I and the nervous sys‑tem, Neurology and Neurobiology, Vol. 51. New York,
Alan R. Liss, pp. 253‑260

2 ) Hayashi, M. (1937) Ubertragung des Virus von Enceph‑
alitis epidemica japonica auf Affen. Folia. Psychiatr.
Neurol. Jpn., 1, 419‑465

3 ) Heffner Jr. R. R. (1976): Arbovirus encephalitis. In
Binford C.H., Connor, D.H. (eds.) Pathology of tropicaland extraordinary diseases. An atlas. Vol. 1. Washin‑gton, Armed Forces Institute of Pathology, 36‑40

25

Jpn. J. Trop. Med. Hyg., Vol. 21, No. 1, 1993, pp. 25‑34

Note

THE DEMOGRAPHIC ATTRIBUTES OF THE PROVIDERS
AND UTILITIES OF THE SERVICES OF TRADITIONALHEALING HOMES IN BENIN CITY, NIGERIAFESTUS IGAHAROSA AGBONLAHOR
Received October 25 1991/Accepted September 1 1992

Abstract: In Nigeria, modern medicine exists side by side with traditional medicine. Despite theadvantage of age enjoyed by traditional medicine, only allopathic medicine is officially recognised. A goodnumber of the literature on the healing systems in Africa is repleted with derogatory comments about theperson and work of the traditional healer (Oyebola, 1978; Ndeti, 1976; Saunders, 1953; Jahoda, 1962; Mbiti,
1976; Uyanga, 1979).
In spite of all these, WHO (1978) has continued to maintain that 80 per cent of the inhabitants of Third
world countries seek health‑help from the traditional healers and has consequently directed their integration
into nations' health care delivery services.
All these heighten our curiosity about the real identity of this set of healers about whom so much havebeen said, but who have some‑how managed to escape the scrutiny of analysts. The provision of information
to fill this vacuum constituted the thrust of this work.
On the whole, the results in section A (Clients) showed that residents in Benin City employ the servicesof the tradomedical practitioners irrespective of social classes. In section B (Healers) we discovered thata good number of the myths concerning the traditional healers were unfounded. Furthermore, that for themost part, healers were not too different in social attributes from the average man in the population and arehighly responsible people.

WHO (1978) defined African medicine as: . . , theintroduced during the colonial rule and today exists
contemporaneously with traditional medical system inmost African countries. It is scientifically based andsum total of practices, measures, ingredients and proce‑practised along the Euro‑american model. Modern

dures of all kinds whether natural or not which fromtime immemorial had enabled the African to guard

medicine is the dominant form of medical practice inmost African nations. Dominance here is synonymous

INTRODUCTION

against disease, to alleviate his sufferings and to curewith government recognition. However, exidences

himself .

abound which suggest a general insufficiency and inabil‑This definition is quite embrasive and adequately
captivates the world view of Africans.
Ndeti (1976), has observed that the knowledge of
medicine is known in all human societies. According tohim, the mere fact that a people has domiciled in ahealth needs of Africans (WHO, 1978; Good et al.. 1979;
Otayula, 1973; Ademuwagun, 1969) .
Consequently, 80 per cent of Africans rely on the
traditional healers to meet their health needs (Oyebola,

ity of modern medicine to successfully cater for theparticular environment for a prolonged period of time is1981) . Part of the explanation for this high utilization ofenough indication that they have to a certain extent
acquired enough homeopathic adaptation to enable themtraditional healing method also lies in the orientation ofsurvive.

modern medicine which sharply contradicts traditional
orientation. Modern medicine is founded on science andAfrican medicine is akin to the one Ndeti describedaccordingly limits it's explanation to what it can empiri‑

above. Modern medinine on the other hand wascally verify. But while it is true to say that the reflection

Department of Socrology Bendal State Umversity, P.M.B. 14, Ekpoma, Nigeria.

26

of scientific ethics in allopathic medicine is in conso‑

50 respondents were drawn from the class of traditional

nance with the world view of western societies, the samecannot be said of Afric,an ･societies, whose views on thehealers, while 50 came from respondents who have at

phenomenon of disease causation incorporate the natu‑
ral and the unnatural. This is evidenced by the dualof traditional healers. The purpose of adding the lattergroup is to enable us cross‑check some of the responses

health‑shopping commonly found in Africa (Asuni,of the traditional healers as well as illuminate the issue1979) .

of .the kind of persons that constitute his clients.

The general attitude of the various governments in
Africa, to the traditional healers has been one of apathy.
Such has led to the official recognition of modern practi‑

tioners only, despite numerous criticisms of orthodox

medicine and high patronage enjoyed by traditional
healers.

Writing on this despicable attitudes to the tradi‑tional healers, Ndeti (1976) observed that he is often
referred to as being the 'Jack of all trades but a masterof none' by his professional colleagues in modern medi‑cine. Like a philosopher, he is said to know everything
about all diseases safe a particular one. Continuing, he
noted that they claimed that his diagnoses and therapies

one time or the other, sought and obtained the assistance

The purpossive method of sampling the universe
was employed. Furthermore, the data were generated
through the use of a questionnaire and indepth inter‑view. The questionnaire was divided into 2 sections: A
and B. Setion B was exclusively meant for the tradi‑tional healers and was designed to elicit information
con.cerning the demographic attributes of healers, themode of training, the practice and ,efficacy of healers
drugs. However, in this present work only the demo‑
graphic attributes was taken into coguisance. Section A
was mainly devoted to bringing forth information relat‑
ing to the social characteristics of the clients of healers.

It suffices to say that the questionnaire took a semi‑

are married by an aura of mystery. While others con‑cluded that because he lacks the necessary scientificstructured form. The questions were open and close
ended. The essence is to allow for a wide range oftraining in medical sciences, he does not appreciate theresponses especially in areas where the subject matterdoes not lend itself to easy grasping. All interviews
were conducted and recorded by the researcher.

magnitude of such things as germs theory and so muchof his works continue to be a mere guesswork. While
those who conceed that he gives herbal prescription also
maintain that they are for the most part unscientific.
Yet others see him as a clever rascal, an extortion‑

RESULTSist and a barrier to the wheel of progress in the rural

Table I Going to the traditional practioner by age

area, while some others continue to refer to them aswitch‑doctors. Writers like Mbiti (1976) , Torrey(1973), Sempebwa (1983) have devoted part of theirworks to looking at this attitude to the works andperson of the traditional healer.

The net result has been a continued mystification of

the work and person of the traditional healer. While

such mythologies and mystifications linger, WHO(1978), has called for the integration of traditional
healing methods into the mainstream of nations' health‑and sex

Ages

Male

Female

1 ‑15

O

O

O

16‑30
31‑45
46‑60
61‑75

7

10

17

Total

8

7

15

11

4

15

2

O

2

22

50

61+

O

Total

28

care delivery services.

A11 these exacerbate our curiousity and further

Section A

inflame the nagging question of who a traditional healer

The data collected under this variable revealed thatis and what sort of people utilize his services. The
provision of information to fill this gap, is the prime
motivator of this work. It is hoped that this will stimu‑

28 males as against 22 females were sampled. It is theopinion of the researcher that it will be premature toconclude that more males than females utilize the ser‑late others to further research in this field and create avices of the traditional healers in Benin City.

basis for comparison.

The reason for this is that since the sampling tech‑nique employed was geared towards interviewing only

METHODOLOGY
The study involves 100 respondents. Of this figure,

those who have received the services of healers, it may
well be that what our samples simply show is that moremales than females were willing to report and were27

consequently sampled. This however does not complete‑beyond secondary form 5. Going further, we discovered

ly remove the oddity in this results, since in the societythat 14 males as opposed to 12 females fell into the semi‑

under study, women are generally saddled with the careof young children.
Age: We can further analyse Table I by looking at

literate cohort. Finally, 8 male clients as opposed to 6
females fell into the literate category.

the ages of respondents. In order to examine thisvariable, the ages of respondents were calibrated asshown above.
As Table I shows, nobody was interviewed in the

IEhe information collected in this section showedthat there tend to be consistency in the pattern ofutilization between male and female clients in the vari‑
ous categories. It is also discernible that the bulk of theclients for both sexes are concentrated in the semi ‑age limit 1‑15 years. We like to believe that this finding

literate class. A probable explanation for this seemingly

is quite apt. It would have been foolhardy considering
the type of dreadful stories that abound concerning thehigh literacy rate is that Bendel State still remains thechuld, 1976 ; Oyebola, 1981) . Thirty‑four per cent of theoldest in the federation and has enjoyed free education
at one time or the other from succeeding administration.
Religion: The religious affiliation of clients formed
another focal point of this work. Clients were asked torespondents fell into the age category 16‑30 years.

state their religious affiliation. Their views were tallied

Another 30 per cent each fell within age limits 31‑45 andunder 3 major religious groups: Islam, Christianity and

46‑60 years respectively. By the same token, 4 per centfell into age category 61‑75 and 2 per cent in cohort 76
and above. It would seem from this distribution that in
Benin City, the bulk of the people who seek the services

ATR. The results showed that 20 per cent of ourof the traditional healers come from age cohort 16‑60
years. It is observable that no significant pattern or
frequency of utilization exists among age limits 16‑30

afiiliation does not affect pattern of utilizing the services

traditional practitioner for a 15 year old boy to seek theservices of one alone (Ndeti, 1976; Torrey, 1972; Uns‑

years, 31‑45 years and 46‑60 years. Similarly, thefindings of only 4 per cent and 2 per cent recorded in age

categories 61‑75 and 76 and above do not look too
strange. It is expected that by the time a man attains

those age brackets, his children would be matured
enough to "cater" for themselves.

We can account for the lack of any significant

respondents were Moslems, 36 per cent Christians andanother 44 per cent ATR worshippers.
It will seem from this observation that religiousof the traditional practitioners.

Marital status: The mar‑ital status of clients is
another area in which subjects were quizzed. It wasobserved that there were 6 males who reported being
single as compared to 9 females. Going further, we
discerned that 21 male clients were married as opposed
to 7 female clients. A male and 4 female respondents
fell under the cohort of those separated. There was no
divorce figure for male, whereas, 2 was recorded for thedifferences recorded in age category 16‑60 years on thefemale clients.

ground that this group contains those who are either

There is not much to say about the findings formales under marital status except perhaps to mention

preparing or just given out in marriage and are anxious
about many "good things" of life and the fact that it also

encompasses parents who for diversified reasons areeither looking after themselves, their children or house‑
hold in general.

Education: This is another area where the views ofthat in the male category, more.married men utilize theservices of traditional practitioners than other cate‑gories.

Table 2 Number of wives/co‑wives

respondents were sampled. Subjects were asked to

No. wives/co‑wives

report on the highest educational qualification attained.

To facilitate this, education was divided into 3 phases:

Male

FemaleTotal

Single

6

9

15

1

3

l

4

2

5

the literate category which comprised of everybody who
had post secondary qualification of any kind, the semi‑
literate group which include everyone who read beyond

3

6

4

2

post primary but not above secondary form 5 and the5illiterate cohort comprising all those who had no formal

N ot reported

education of any kind, or read below primary 6. Their

Total

6
2

8
3

O

1

5

8

13

28

22

50

responses were organised and further regrouped interms of sex. The results showed that under the literate

Number of wives/co‑wives: Another demographic

grade, 6 male respondents as against 4 females read

attribute explored in this work, is the number of wives/

28

co‑wives traditional healers' clients have. As before,clients were asked to state categorically, the number ofwives in the case of men and co‑wives in the case of
women. The result is tabulated in Table 2. It is seenfrom the table that 6 males and 9 females were unmar‑
ried. The other respondents for both sexes were mar‑

It is striking that as many as 15 respondents refused
to disclose the number of children they had. The expla‑
nation for such manifestations lies in the people's worldried.

clients is yet another major social characteristic thatThree male clients had I wife each while only 1
female client had I co‑wife. Five males had 2 wives
each, while I female client had 2 co‑wives. Six malewas sifted in this work. The response pattern is asfollows: 6 per cent were into farming, 36 per centsubjects and 2 female clients maintained that they had 3

being engaged in teaching. Another 4 per cent related
nursing, 16 per cent were drawn from the class of civil
servant, 10 per cent were students while others/un‑categorised accounted for the remaining 24 per cent.
It would appear from these findings that in Benin

wives and co‑wives respectively. Only 2 male respon‑dents and I female reported that they had as many as 4

wives/co‑wives. Finally, I male reported having 5
wives whereas, no female client reported having co‑wives to that tone. It will be observed that as many as

5 male subjects and 8 female interviewers refused toreport on this variable under discussion. If we add thesefigures to that reported for the single of both sexes, theleft‑over will be too few to allow any broad generaliza‑

tion. We shall therefore rest the matter at that.

Male

O

l‑3
4‑5

Occupational group: The occupational grouping ofreported that they were traders. Four per cent disclosed

City, traders form the bulk of the clients of the tradi‑tional healers. This finding is in order. Moreso, when
we recall that as many as 22 males and 18 females fell
into the semi‑literate category.
At first glance, the 6 per cent recorded by females
appears puzzling. Especially as 28 per cent of the clientsambivalence if we recall that this research was conduct‑

Female

Total

9

13

2

fear of evil befalling them.

were illiterates. However, we are less likely to feel such

Table 3 Number of children
No. children

view which forbids the counting of one's children for

ed in an urban centre.

Table 4 Income level

3

Income per year
in Naira

3

2

5

6 ‑10

8

O

8

11‑15

4

O

4

16 +

2

O

2

0‑499
500‑999

1

2

N ot reported

5

10

15

l , OO0‑1 , 499

48

1 , 500‑1 , 999

48

2 , OO0‑2 , 499

918

2 , 500‑2 , 999

510

3 , OO0‑3 , 499

l2

3 , 500‑3 , 999

OO

4 , OO0‑4 , 499

4

8

Total

28

22

50

Number of children: The number of children
healers' clients have also constitute one of the demo‑
graphic variable that was taken into account in thiswork. This is depicted in Table 3. It can be seen fromthe table that 4 male respondents and 9 female subjects
have no children. Going further, 2 males and I female
reported that they had I to 3 children. Three male and2 female clients also reported that they had 4 to 5
children whereas, 8 female respondents and no female
subject had between 6 and 10 children. Finallyy, 4 males
claimed they had up to 11 but less than 16 children while

only 2 males had up to 16 and above children. No female
client was observed in the last two categories.
It is queer especially at first glance, to see that no

female client had up to 6 children. The finding isnevertheless apt considering the fact that we located themodal class for female clients to be in the age cohort 16‑
30 years.

Respondents % Representation
2

5 OO0+

918

N ot repoted student

12

24

Total

50

100

Income level: By way of finalising our discussion,
subjects were asked to state their annual income. The
report was then ranked and presented as in Table 4. We
choose here to proceed without order of place. Two percent of the clients claimed they receive less thanAnother 2 per cent admitted getting more than500.

1:500 butless than N 1,000 and yet another 2 per cent professed
getting more than N3,000 but less than N3,500. Similar‑ly, 8 per cent informed the interviewer that they earnmore than 1:1,000 but less than :1,500; while yet29another 8 per cent claimed they gross below
above:4,500 but

1:4,000.

We had another tie in the modal category. The first18 per cent claimed they earned more than
2,000 butless than N2,500, while the second 16 per cent claimed
they generally earn at least 5,000. Finally, we had
another 24 per cent ranging from students to those who
outrightly refused to declare their annual income.

with this observation.

Education: The educational attainment of healers
was one of the attributes that was considered in thiswork. In going about it, healers were asked to reporton the highest level of education they attained. For easy

attract more fines. We are however unable to tell if suchreferencing, we divided education into 3 major class asfollows: the literate category, comprising of everyone
who read beyond secondary class 5, the semi‑illiterateclass which includes everybody who attained primary 6
but not above secondary class 4; and the illiterate co‑hort, made up of those who attained below primary 5 ornone at all. Their responses were further regrouped interms of sex. The results show that only 6 male respon‑factors were at work here.

dents had educational attainment beyond secondary

This phenomenon of refusal to declare annual in‑come is usually not unconnected with the fears of
respondents, specially among the not too literate group,

who probably feel that reporting the exact amount will

Section B
Table 5 Age by sex

form 5. No female was observed in this category. Goingfurther, 21 male subjects as opposed to one female fell
into the semi‑literate division. Finally, 9 males and 13
females were found in the illiterate class. From the

Ages

Male

Female

Total

1 ‑15

O

o

O

16‑30
31‑45
46‑60
61‑75

7

o

7

attainment beyond secondary 5, and it would appear

10

4

14

that in this bid, the female sex are more disadvantaged.

19

9

28

O

76 +

O

o

O

Total

36

14

50

The characteristics of traditional healers: Table 5
despicts the age by sex of the traditional healers in
Benin City. Chronologically, no respondent was to beobserved in the age bracket 1‑15 years. Only 7 malesubjects fell into age cohort 16‑30 years. No female wasobserved in this category, 14 respondents, comprising of

IQ m les and 4 females fell into age category 31‑45
years. Age group 46‑60 years represents the modal

findings in this work, we can conclude that most practis‑

ing healers in Benin City today do not have educational

Religion: The religious affiliation of healers formed

another area of inquiry in this work. Healers were tostate their major religion. When collated, their views
led us to propose 3 major religious divisions. This was
further expressed in terms of sex. The results showedthat 13 out of our sample of 50 healers are Moslems.
Closer analysis reveals that they are all males. Similar‑

ly, we found that out of 7 respondents who claimed thatthey are Christians, none is a female. Moving further,
we found that of a total of 30 respondents who reported
subscribing to African traditional religion (ATR) , 16
are males while females accounted for the remaining 14.
This finding suggests that the bulk of the traditionalclass. We had a total of 19 males and 9 females in thishealers in Benin City are believers in ATR. It is remark‑zone. Finally, while age limit 61‑76 yeaf,s had･･only one

able to point out that on further scrutiny, we discoveredthat none of the 7 Christian‑healers employs the art ofdivinition in their work. They specifically claimed to be

respondent, a female, no interviewer was found in theage grade 76 years and above.

Two comments can be made about Table 5. First,
a look at age limit 1‑30 years would reveal that only 7
healers are in this category. When these 7 respondents

were scrutinized, the researcher discovered that they
were slightly under 30 years. It will therefore appear
that in Benin City, Traditional healers of both sexes doherbalists. Conversely, we found that nearly all 30
believers in ATR utilize the divinition technique. It
would therefore seem that the religious belief of the
traditional healers in Benin City affect their scope ofpractice and that in this, the Christian‑healers tend to becially as no female was observed in this age division that

more conservative and have lesser scope of practice,
while the ATR=healers have the widest.
Marital status: The marital status of healers for‑med another area that was scrutinized by this work. As

male healers commence practice earlier than female

before, we divided marital status into single, married,

healers in Benin City.. ̲ l,t would be fascinating to know

separated and divorced categories. When tampered

if the marital status of female clients has anything to dowith another variables, sex, the response pattern showed

not commence commercialized practice until they are atleast 25 years of age. Secondly, it would appear, espe‑

30that while 5 male respondents, fell into the unmarried or

single category, no female was observed in this group.
When expressed in terms of percentage, this male figure
comes to 14.1 per cent. We noticed that 31 of the male
healers were married. When ranked in terms of percent‑age, this figure came to 85.9. Again there was no female
respondent in this cohort. The reverse is however thecase when we examine the cases of separated anddivorced categories. It is remarkable to observe that no
male healer fell into any of these compartments, unlike
21.4 per cent (3 persons) and 78.6 per cent (11 persons)recorded by female healers under the separated anddivorced categories respectively.
From the analysis of this table, it would appear that
there are relatively few, if any male traditional healers

in Benin City who are unmarried. This finding is suppor‑

Three disclosed that they had one wife each. Further‑more, 7 claimed that they were married to 2 wives each.

Anotherreported being respectively married to 3

wives, while 3 others recounted 4 wives each. Finally, 2

healers relayed being married to 5 wives each. It isremarkable that as many as 10 healers refused to dis‑close the number of wives they had. By way of cross‑checking the entire findings in this section, female
healers were asked to state if they had any co‑wives
either while they were living under the same roof as
their husbands or separated. It is significant to point out

that they all agreed that they had at least one co‑wife.
The implication of this report is that it tends to define

the marital situation in Benin City as a whole rather
than wholly relate to the traditional healers. Moreso
when it is not clear if the female healers were marriedted by the fact that we had earlier located the modal
class for male healers in the age category 46‑60 years.
Furthermore, it would appear from the absence offemale healers in the single and unmarried categories
and by the fact of their concentration in the divorced
category, that women who are single or who still living
under the same roof as their husbands do not engage inpractice or commercialized traditional healing. Thisto male healers at the time they were married. But since

position is strengthened by the fact that all 21.4 per centat least 2 wives.

the traditional healers interviewed in this work also
reside in Benin City, then it could be said at least in part,that the report could also be applicabe to them. If thisbasic premise is accepted, then it will not be a far
fetched generalization if in addition to our earlier stanceabout the male traditional healers in Benin City being
married, we further add that they have on the aVerage,

who are still married are separated from their husbands.
It would therefore be reasonable, based on this finding to

say that the bulk of the practising female healers in
Benin City are divorced.
In our consideration of the ages of female healers,
we mentioned that it would be worthwhile to see if themarital statuses of female healers have anything to dowith their commencing commercialized practice late. In

going about this, we ranked the reported marital

Table 6 Number of children
Respondents% Representation

O

5

10

1‑3
4‑5

4

8

No. children

2

4

6 ‑10

8

16

11‑15
16+

3

6

5

10

Not reported

23

46

Total

50

100

statuses of female healers by their ages. As before, wetore marital status into single, married, separated anddivorced. Age on the other hand was ranked from 1‑15,
16‑30, 31‑45, 46‑60, 61‑75 and 76 and above. The results
showed that no female healer was found under 30 years.

was another sub‑heading that featured under demo‑

We observed that the 3 who fell into the separated

graphic attributes. The response pattern or distribution

category also fell into the age cohort 31‑45 years. Of theis shown in Table 6. It is readable from the table that
10 per cent of the respondents had no children. Eight perremaining 11 healers who fell into the divorced category,

The number of children each traditional healer has

lO fell into age grade 46‑60, while one fell into age
bracket 61‑75 years.
What can be said about this finding, is that it cor‑cent had a range of 1‑3 children, while another 4 perroborated our earlier assertion that women who are

Another 10 per cent reported having 16 or more children.

single or still live under the same roof as their husbands

Again we observed as in the discussion of number of

do not engage in commercialized practice.
Number of wives: The number of wives traditional
healers have constituted another analytic unit of thiswork. As the results had it, 5 healers were unmarried.

wives, that as many as 46 per cent of the respondents did

cent had 4‑5 children, 16 per cent of the healers had 6‑10

children each, while 6 per cent had 11‑15 children.

not disclose the number of children they had.

31

than N1,000 but less than

Table 7 Occupational distribution of traditional
healers

while 8 per cent maintained they netted more than N

Respondents % Representation

Main oecupation

Traditional prac‑

40

80

Farming

5

10

Trading3

6

Others

2

4

Total

50

100

:1,500, 12 per cent agreed

that they grossed more than N 1,500 but less than 2,000
2,000 but less than

2,500, 4 per cent attested to the factthat their annual income was greater than : 2,500 but
less than :3,000. Only 2 per cent reported that theirannual income was greater than N3,000 but less than N
3,500. And while 2 per cent testified earning between N
3,500 and N3,999, another 6 per cent related getting
above 1:4,000. Finally, 4 per cent refused to disclose
their annual income.

titioriers (excluding
spiritual healers)Occupational group: Table 7 shows the occupa‑

DISCUSSION AND SUMMARY

tional distribution of traditional healerst And as thetable w. ould reveal, as many as 80 per cent of the tradi‑

In this section, we shall attempt to revisit some oftional healers interviewed engage solely in the art ofhealing. Ten per cent are into farming, 6 per cent inour earlier findings in the hope that more lasting conclu‑

Unlike the case of the healers included in the 80 per

sions can be made about them.
In our discussion about the sex of the clients oftraditional healers, we discovered that more males

cent, the latter groups regard traditional healing as

disclosed that they utilize the services of healers andsecondary occupation. It should be pointed out too, thatsome traditional healers included in the 80 per cent havewere consequently sampled. This result appears queer

other avocations. We however did not bother to record
these as we were only interested in major occupations.

findings, Oke (1982) explained that there is a tendency

trading activities and 4 per cent in others.

but is not unique. When confronted with the sameamong Yoruba women to report less on this issue for

Based on this finding, we can safely say that majority offear of being prosecuted. Whether such factors were atthe people who practice the art of traditional healing inwork in this study is difiicult to say, but suffices to say

Benin City, regard it as their main occupation. If thisclaim is authentic, then we have reason to believe thatthey find the art profitable. Whether this is correct or
not will be determined by their reported annual income.

that as Africans, a lot of grounds exist for this kind of

occurence. Such stance is not supported by Uyanga(1979) who discovered in his investigation of the native

Respondents % Representation

1 499
500‑999

2

4

17

34

1 , OO0‑1 , 499

1224

1 , 500‑1 , 999

612

2 , OO0‑2 , 499

48

2 , 500‑2 , 999

2

4

3 , OO0‑3 , 499

1

2

Not reported

450

doctors in his area of study that children and married
women form the bulk of the clients.

Furthermore, we observed that no significant
differences exist in the patter,h of utilization among age

brackets 16‑30, 31‑45 and 46‑60 yearS. This finding is

amply supported by Oke (1982) who concluded after athorough study of 200 clients that adulthold rather thanage per s*ex was the all important factor when consider‑ing the utilization and contact with traditional healers.

2

3 , 500‑3 , 999

Total

100

The traditional healers who formed the samples forthis work were all asked to state their estimated annual

income. Table 8 shows the distribution. Looking at thetable, it can be observed that 4 per cent claimed theirannual income was less than N500, while 34 per c6nt
reported they earned more ,thanIn our consideration of the ages of clients, weobserved that nobody under 15 years was interviewed
and we gave a seemingly plausible explanation for that

Table 8 Annual income
Income per year
in Nairapractice.

1: 500 but less than:l,OOO. Another 24 per cent estimated that they get more

Our study of the educational background of clients
did not show any significant relations in the pattern ofutilization among the literate, semi‑literate and illiter‑

ate cohorts. This finding is not wholly supported by
Uyanga (1979) who discovered that illiterates form thegreater proportion of the clients of native doctors heinterviewed; whereas, educated persons form the major‑
ity of the clients of the spiritual healing homes hesampled.

32

We observed in our consideration of religious

which links illness to other aspects of social life andaffiliation of clients, that no significant gap exists in thesubsumes the latter under one causal fabric of man,nature and soeial relationships. It is such thought
pattern which belies the psychosomatic conceptualiza‑tion of disease and attending illness behaviour ofform of utilization of the services of the traditional
healers. A seemingly rational explanation for this isthat Bendel State is renownedly peopled by a multiplic‑
ity of ethnic groups each of which has it's own belief
system. We know from the assumptions of culture area
theory that a trait usually diffuses outwardly from theconcentric centre only after the latter is suffused. If thissubmission is constant, then it will not be an overAfricans (Chilivumbo, 1976; Namboze, 1983; Crain, 1975;
Pfifferling, 1976; Worsley 1982) .

Our consideration of the annual income of healers
showed that 62 per cent of our sample stated that theygrossed less than N 1,500 per annum. This finding is

generalization if we take the standard of utilization of
the services of the traditional healers among the three

spurious and fails to tally with the fact that most practi‑

listed religious group as the cultural trait and assert that

Besides, it negates the fact that most of them eagerly
reported that they find their practice profitable. Our

having lived together in the same geographic region fora nurnber of years, there tend to have developed feelingsof oneness that may have informed this indiscriminate
or diffused system of utilization.

The findings in the female category under marital

status deserve some comments. The figures appear
spurious and sharply contradict our assertion thatfemale clients reported less than their male counterpartsfor fear of persecution. If one projects this argument,

one expects the divorced women to report more thantheir married counterparts. The results of this work did

not however indicate this. Perhaps divorced women
have less at stake than their married counterparts. We
are however unable for want of date to comment on theextent and nature of relationship under which such anassumption holds.
The findings in this section did not validate ourworking hypotheses:
1 . The higher the educational attinment of a person,
the lesser the utilization of the services of the tradi‑tional practitioner.

2 . The higher the annual income of a person, the lower
the level of utilization.

tioners take traditional healing are as vocations.

thinking is that healers under‑reported on this variable.

This is even more obvious by the fact that most of thehealers interviewed live in at least 2 rooms. If we takethe average rent per room to be
25, then it is difficult
to see how they can afford to live on such a paltry sum.
This thinking is further supported by the fact that one
practitioner whose 1: 3,000,000 tradomedical centre hasreached an advanced stage, reported an annual incomeof one Kobo. Couple this with the fact that healersconfirmed that they charge at least
1: 500 for cases
involving mental patients and other serious ailments
like sterility, then it will be clear that something is
missing.

This finding is supported by that of Erinosho andAyorinde (1985), who concluded after an extensive
work on the traditional practitioners, that they find theirpractice profitable.

When respondents refuse to report on annual in‑come, it usually arose from mistrust and illiteracy.
Whether such explanation can be made in this work isdifficult to say. Moreso, when we discovered that thebulk of the practitioners in Benin City had one form of

3 . Divorced female clients utilize the services of theschooling or another. Perhaps their responses weretraditional practitioners more than married female

shaped by the current crime wave. It is just probable.

clients.

4 . African traditional religionists utilize the services

Our analysis of the age by sex of respondents

utilization of the services of the traditional practioners

revealed that most traditional healers in Benin City
were within the age category 46‑60 years. We observed
too that this age cohort was closely followed by 31‑45
years. Combined, they accounted for a total of 74 per

is irrespective of social classes. This finding tallies withcent of our sample. The implication of this is that mostthat of Oke (1982) among the Yoruba and is further
complimented by Jahoda (1962) who concludes that theof the traditional healers in Benin City are fast aging. It

fact that the traditional healer enjoys the patronage ofthe educated class is vital in accounting for his presence

knowledge, we may never be in a position to benefitof the traditional practitioners more than Christians.

The implication of this is that in Benin City, the.in̲ our midst.

It is more than likely that the real factor at work is

the undifferentiated nature of African thought system

is our thinking that unless something is done to tap theirfrom their stock of knowledge less alone transmit themto posterity. The maguitude. of this further dawns on us
when we realise that 80 per cent of Nigeria's estimated
80 million people seek help from the traditional healers33(WHO, 1978) .

age they are likely to enjoy.

In our analysis of he level of education attained by

Such cosmogenic explanation was also found attraditional healers, we found that unlike the male
respondents who had their modal class located in thework when in the deliberation on the number of wives

semi‑literate category, the females had 92.9 per cent offailed‑ to report on how many of each variable they had.

their respondents falling into the non‑1iterate group.

The Edo forbid people to count the number of children

The first impression one gets about this finding is that it

or wives they have for fear that evil might befall them.
This phenomenon has also been reported by Oke (1982) ,is spurious. It is possible to account for the figure
recorded by the male healers by claiming that Bendel

and children, we discovered that many respondents

among the Yoruba. It would seem from these findings,

State as the oldest in the Federation, has had succeedingthat the practice of traditional healing in Benin City, isgovernments offering universal free education at one
time or another. Such explanation does not tell us why

still very much regulated by the traditional beliefs of thepeople.

the female did not take advantage of it. The only

The findings in this work have demonstrated thatseemingly plausible explanation for this phenomenon isthat there used to be a belief among the Edo speaking
people that it is wasteful to educate female children.
The on‑going women liberation by our women folk is amost myths about the person and work of the traditionalpart of the moves made to disabuse the minds of the(1981), held the inability of one of his respondents topopulace about such beliefs.
While considering the marital status of healers, we
noticed that the bulk of the male healers were within theage cohort 46‑60 years, and were married. The fact thattake blood pressure as necessary indication of impo‑
tance to cope with hypertension and cardiovasculardiseases. It should be acknowledged that even within

no male healer was fecorded under separated and divor‑
ced categories may in part be accounted for by the fact

would still have been statistically too insignificant tohealer cannot stand to any considerable degree ofscientific scrutiny. In his work on the traditional
healers' associations among the Yoruba. Oyebola

allopathic setting, the figure, one out of a sample of 156

that the healers interviewed for this work generally live

allow, such a generalization.
The real issue however, is that even though both thein the city. One way they can earn respect and possiblypractitioners of the orthodox and traditional healing

attract clients, especially those of the opposite sex, is tosystems have a common goal in mind and may in someshow that they are responsible men. Another is age.

cases serve the same population in needs as Good (1979)

The Edo amongst whom this work was carried out,

rightly observed, they differ in terms of availability,

frown on a situation in which a man deliberately decides

quality of care, technology and social adaptability.
Indeed, the ability to take blood pressure is merely ato remain unmarried long after having reached fecun‑dity. Yet another reason may be seen in the fact thatwomen prove a great helping hands especially withhousehold chores. Such services generally liberate
husbands from such tasks and thus permit them todevote more time to their works.
Conversely, we found that most female healers wereabove 45 years old and divorced. Again, the reason forthis lies in the cosmology of the people. Among the Edo
speaking people, it is believed that such a phenomenon
as menstrual cycle in women lessens the degree of inter‑means rather an end in itself. Therefore, the presupposi‑tion that the tradomedical practitioner must acquire thisability denies the efficacy in the argument about theinventive nature of mankind, confuses means with ends,
as well as fails to acknowledge that diagnosis, treat‑ment, prognosis and the methods adopted are a productof a people's immediate environment and global conce‑
ptualization.

Also to be suspected, is the emphasis on empiricalverification. It would appear that most analysts gloss
over the fact that illness in Africa is a matter of social

action between the people of the corporeal world andthose of spiritual. If one took the average menopause
age of the African woman to be somewhere between 34
and 45 years, it would appear that there is ground for

relationship and that African conceptualization of theaetiology of disease goes beyond symtomological treat‑

this explanation. For while the female healers who fell

pure science, beliefs about the existence of such phenom‑

within age cohort 35‑45 and who live separated fromena as neutrons and viruses thrive despite our inability

their husbands may be given benefit of doubt and hence
patronized, the same may not apply to female healers oflesser age bracket as it raises the question of their

to see them with our naked eyes. If this does not shakeefficiency and positively jeopadize the degree of patron‑

work of he traditional healer as a diversion. Indeed, as

ment. It is a recognised fact that even within the field of

our belief in their existence, then it is only logical to see

the claim of the aura of mystery which surrounds the34

Chilivumbo (1976) , rightly observed, the cure that ismeaningful to the patient is that which sets his mind atrest, frees him from his anxieties, reinstates in thepatient will to live and restores him to a normal fun‑ctioning within a therapeutic community.
We discovered in the cause of this work that thelabels: 'extortionist', 'clever rascal' and 'Jack of all
trades' cannot be said to refer to the bulk of the tradi‑tional healers in Benin City. This observation is cor‑roborated by the work of Erinosho and Ayorinde (1985)
who while noting the 'deep‑seated suspicion' in which
western trained doctors hold the traditional healers ‑because of what they called 'the teaming patronage' thelatter enjoy‑submitted: """"a very siguificant propor‑
tion in the society had greater confidence in the thera‑
peutic skills of the traditional healers".

On the question of the often made mistake ofcategorising witch doctor and witchcraft as the same
person, Torrey (1972) observed that such a relation is
not a relationship but a colonial imputed semantic
association. He further argued that all cultures havepeople who play the role of doctor or healers and mostcultures too have the people who play the role of awitch. The same argument can be made in the case of
the allusion to the traditional healer as a 'clever rascal'
and an 'extortionist'.

Mbiti (1976) has maintained that many
trademedical practitioners in Africa are deeply involvedin the maintenance of social order and in preserving
cultural institutions. This argument has been streng‑thened by the works of scholars like Ademuwagun(1969) and Ndeti (1976).
Two ways to end this suspicions and to disabuse thefor therapeutic meaning. In: Medical anthropology(Grollig, J.S. et al. eds.), Mouton. Paris
4 ) Crain, B.J. (1975): Understanding ritual. p 0cess in the

medical setting. In: Psychological anthropolbgy(Thomas, W.R. ed.) Mouton, Paris
5 ) Erinosho, O.A. and Ayorinde, A. (1985) : Traditional
medicine in Nigeria. A study prepared for the Federal
Ministry of Health, Lagos, Nigeria
6 ) Good, C.M. et al. (1979): The interface of dual systemsof health care in the developing world; toward healthcare policy intiative in Africa, Social Science andMedicine
7 ) Jahoda, G. (1962): Traditional healer and other institu‑
tions concerned with mental illness in Ghana, Int. J. Soc.
Phychiat.

8 ) Mbiti, J.S. (1976): African religions and philosophy,

Heinemann, Nairobi
9 ) Namboze, J.M. (1983): Health and culture in an African
society, Social Science and Medicine
10) Ndeti, K. (1976): The relevance of African traditional
medicine in modern medical training and practice, In:
Medical Anthropology (op. cit.)11) Oke, E.A. (1982) : Traditional health services: an investi‑

gation of the providers and the level and pattern ofutilization among the Yoruba, Ibadan: Unibadan Depart‑
ment of Sociology12) Otayula, W. (1973): Native and eastern healing: thedilemma of east African psychiatry, J. Nervo. Ment. Dis.
13) Oyebola, D.D.O. (1981): Proffesional association ethics

and discipline among traditional healers of Nigeria,
Social Science and Medicine
14) Pfifferling, J.H. (1976) : Medical anthropology, mirror
for medicine, In: Medical Anthropology (op. cit.)
15) Saunders, L. and Hewes. G.W. (1953) : Folk medicine
and medical practice, J. Med. Educ.
16) Sempebwa, J.W. (1983) : Religiosity and health behav‑

and to inculcate in the curricula of medical students iniour in Africa, Soc. Sci. Med.
17) Torrey, E.F. (1972): What western psychotherapists canlearn from witch doctors, Am. J. Othropsychiat.

tropical Africa, a knowledge of our cultural melieu.
Sempebwa (1983) has also made this call.

18) Unschuld, P.U. (1976): Western medicine and tradi‑tional healing systems: competition, co‑operation ormind of the populace is to undertake more researches

integration?, Ethics in Science and Medicine

19) Uyanga, J. (1979): The characteristic of patients of1 ) Ademuwagun, Z. A. (1969) : The relevance of Yoruba

spiritual healing homes and traditional doctors in south‑
eastern Nigeria, Soc. Sci. Med..
20) WHO (1978) : Primary health care, report of the interna‑

medicine men in public health practice in Nigeria, Publictional conference on primary healing care, Alma‑Ata,

REFERENCES

Health Report2 ) Asunni, T. (1979): The dilemma of traditional healing
with special reference to Nigeria
3 ) Chilivumbo, A.B. (1975): Social basis of illness: a search

USSR.
21) Worsley, P. (1982) : Non‑western medical systems, Ann.
Rev. Anthropol.

35

日熱医会誌．，第21巻，第1号，1993年，35−38頁

シンポジウム報告

欧米先進諸国における熱帯医学教育機構
板
平成5年1月15日

倉に関する教育について付記する。

J．Muller−Eberhard（ハンブルグ熱帯医学研究所所長・教授，ドイツ）：

ハンブルグ熱帯医学研究所（正式名称はBemhard
Nocht

Institutefor

Tropical吾

受付／平成5年1月18日

長崎大学熱帯医学研究所（1992a，b）は，1942年（昭和17年）に旧制長崎医科大学に附設された，東亜風土病研究所をその前身としており，1992年（平成4年）に創立50周年を迎えた。その記念事業の一環として，「欧米先進諸国
における熱帯医学関連研究所の現状とその展望」と題する
国際シンポジウム（lnstitute of Tropical Medicine，
Nagasaki University，1992）を開催した。近年世界情勢
は，東西関係の崩壊，南北問題の複雑化，民族問題の勃興，それに政治，経済問題等が絡み，極めて多様化しつつある。
途上国の多くが占める，熱帯地域における国際情勢も例
外ではなく，困難な諸問題に直面しつつ，目まぐるしい変化を示している。このような状況のもとに，欧米諸国の著
名な熱帯医学関連研究機関における代表的研究者に，どのような現状認識と，将来展望を持って活躍中であるかを発表と討議をして頂き，我々の今後の実践の場に生かしたいと考えた。各演者の発表内容の中から，熱帯医学教育に関する部分について，これまでに把握できた部分を紹介し，末尾に長崎大学熱帯医学研究所で行われている，熱帯医学

Hans

英

Medicine，Hamburg）は，

ハンブルグの衛生局（Department of Health of Ham−burg）に所属している。感染性熱帯病の患者の診断と治療，および熱帯医学の教育と研究が使命であると考えてい受理

1906年Brusselsに設立された。1933年に，主な港町である
Antwerpenへ移転された。当時は，植民地省に所属していた。1960年，アフリカにおける旧植民地領の独立とともに外務省に所属したが，後に教育省（Ministry of National
Education）に所属するようになった。しかし研究活動領域

は，さらに中央アフリカヘも拡がった。1987年には

inpatient departmentはアントワープ大学病院へ移管した
ので，研究所では10ベッドを持つのみとなった。1991年には連邦制の結果，他の大学も同様であるが，地域の教育省（Regional

FlemishMinistryof

Education

andCulture）に所属し，現在は独立した研究所である。所員は240名で，うち38名は学士号（universitydegree）を持った人々，すなわち医師，獣医，生物学者である。ほかに何人かの，外部研究費による研究員がいる。
以下，教育について述べる。まずはじめに，医師（post−
graduate）を対象としたコースがある。このコースは，熱帯において主としてNGOで働く希望者を対象とし，6カ月コースである。これは言語を，FrenchとFlemishとに分けて行っている。受講者の数は過去3年は毎年80名で，うち半数はベルギー人であり，他はヨーロッパをはじめ他の国の人々であった。10年前は，この2倍の人数であった。
生物学者や薬学者も，ときには受講者として加えている。
2番目に獣医や農学者を対象とした，9カ月のコースがある。毎年20名を採用し，熱帯における獣医学や酪農を教えている。3番目に，看護婦コースがある。これは1年以上の経験者を対象としており，4−5力間で年2回開いていを持っている。1988年以前の40年間，医師のための熱帯医
学と寄生虫学の3カ月のコースを，毎年行っていた。しかし1988年に根本的改組を行い，現在では疾患指向の基礎的る。言語はFrenchとFlemishのクラスがあり，受講者全部で約180名である。受講者の1／3はベルギー人で，他はヨー
ロッパ，スイスなどから参加している。4番目のコースは途上国の有資格者，すなわち学士などの学位（degree）を持ち，熱帯現地で活躍する者を対象としている。これには，

研究（desease−oriented

以下の4コースがある。1）Public

る。研究所は西アフリカに，野外調査基地（丘eldbasicstation）

research）を主体としていコースで，Intemational

る。

Paul

L．Gigase（アントワープ熱帯医学研究所副所長・教授，ベルギー）：

アントワープ熱帯医学研究所（正式名称はPrince
LeopoldInstituteofTropical

Medicine，Antwerpen）は，

Coursein

Healthのマスター
HealthDevelopment，およびHealth Plammcation and Managementが専門のコースである。FrenchとEnglishのクラスがある。10カ月コースで，毎年40名である。2）Tropical Biomedical
Sciencesのマスターコースで，目的はdisease controlである。12カ月コースで，毎年20名である。3）Tropical

長崎大学熱帯医学研究所
この内容は，第17回日本熱帯医学会九州支部大会における，シンポジウム「熱帯医学教育の理念と現実」（1993年1月15日，長崎市）
において発表したものの一部である。

36

Veterinarian Sciencesを専門とするマスターコースで，Ph・D・も取れる可能性がある。研究所はその他，途上国におけるいくつかのコースに参画，参加することもある。Bur・

undiや，WHOによる，中央アフリカなどにおけるコース
がその例である。

専門家の養成に関する問題としては，1）自国人（ベルギー人）の医師の希望者の減少，帰国医師の社会復帰の困難性，看護婦に関しては数の不足および国内における要求が多いこと，2）途上国における仕事（熱帯医学）の，専門的要求に対応できる医師の教育が，十分になされていない
こと，3）国外で働くことに対する，自国社会の認識が薄
いこと，などがあげられる。

今後の見通しあるいは方針として，以下のことが考えられる。Publichealthにおける専門化は，ますます進むであろう。途上国での専門家は増えるが，工業国からの専門家は減少するであろう。Ph．D．などに至るような，教育の高度化に対応できるようにしておくべきである。看護婦に対しては，通常のトレーニングはせず，instructorとして活躍できるような，高度の専門的教育（MastersDegree）を目指すべきである。コンピュータを駆使した教育を，第3国でも応用したい。数週問単位のトレーニングコースを，国外で開きたい。輸入病に関する最小限度の教育などは，各大学でやるべきことで，専門的研究機関でやるべきことでは
ない。

David

H．Molyneux（リバプール熱帯医学研究所所長・教授，イギリス）：システムコース（HealthInformation

System）をやってきたし，またザイールにおいて，地域健康コース（Commu・
nity HealthCourse）を，言語としては，Ffenchを用いて行うコースとして設立しつつある。これらは，トレーニン
グコースの将来構想となるべきものである。我々の歴史的活動のなかで，もっとも成功したものとして，25年前にバンコクのMahido1大学熱帯医学部の創設がある。これは，Prof．Brian Maegraithの将来構想によるものであった。
これにより，東南アジアー帯のネットワーク作りに役立っている。そして多くのPh．D．を，リバプールから出したのである。一般に短期コースは，コストの点でも助かる。ちな
みにPh．D．のコースであると，＄100，000かかる。NGOにしても，コース作りのことも是非考えてもらいたいもので
ある。

Kerl

A．Westem（NIH，国立アレルギー・感染症研究

所国際研究部部長，アメリカ），RichardM．Krause（NIH，国立アレルギー・感染症研究所元所長・Forgarty
国際センター顧問，アメリカ）：

NIHの国立アレルギー・感染症研究所（正式名称はNational

InstituteofAllergyandInfectious

Diseases，

NIH，Bethesda）では，原則として国外での研究活動基金は認めていなかったが，Public Health Service，特に，
AIDSに関して1988年から，アフリカとカリブ地方における研究が認められるようになった。トレーニングについて
は，主として，所内の研究室で研究活動の実践の場において行われている。

リバプール熱帯医学研究所（正式名称はLiverpool
Schoolof

TropicalMedicine，Liverpool）は，Sir

AlfredLewis Jonesによって率いられた実業家団によって，1898
年11月に設立された研究所である。当時リバプールは第1の港湾都市で，英国の熱帯地域における利権を握っていた。
TropicalMedicine
tionalHealthなる用語はいまや陳腐で，Intema・なる用語を好む向きもある。当研究所は，

University ofLivrepoo1の附置研究所である。大学院課程（postgraduateteaching）を持っている。教育も研究も目指すところは基本的には，tropical health problemである。教科課程は途上国の二一ズに応じて，弾力的なものでなければならない。研究室内研究だけでなく，熱帯野外活動の面でもPh．D．を取得するに至るような，高度な研究活
動のトレーニングを行わなければならない。このことは，学生のみならず教官にも要求されるべきものである。教育の質に対する監査と，すべてのコースについての評価がなされるべきものである。それらのコースは今後，地域的にどこでなされるべきかを考えねばならない。我々は伝統的に本国の研究所で行ってきたが，当研究所では地方病が存在する地域に，専門家および専門的技術を移転（輸出）することを考えている。地域特異的な問題に目標を絞れば，経費も有効に，また指導者の訓練にも役立つのである。当研究所ではすでに，インドにおける母子健康コース，スーダンにおける疫学コース，中央アメリカにおける健康情報

HarisonC．Spencer（チュウレン大学公衆衛生・熱帯医学部長・教授，アメリカ）：

チュウレン大学公衆衛生・熱帯医学部（正式名称は
TulaneUniversity

Schoolof

PublicHealthandTropicalMedicine，New Orleans）は，1834年に設立された。当時，
New Orleansではコレラ，黄熱，マラリアなどが存在していた。現在，米国における熱帯医学に関する唯一の学部で，寄生虫学や熱帯病の研究，教育に取り組んでいる。種々の講座（department）やセンター（center）と連携した活動をしている。当学部には5講座（Intemational Healthand
Development，Cell and Molecular Biology，Immunology，Microbiology，Biostatistics and Epidemiology），Adult

andPediatricInfectiousDiseasesSections，3つのセンター（Primate Centerなど），それに研究所などがある。
学生数は約500名で，うち25％は国外からである。国籍は米国を入れて，62力国である。Publichealthではラテンアメリカ，サハラ以南，特に西アフリカからの保健（health）に関する専門家養成を行ってきた。PeaceCorpsとも深い関係を持っている。取得できるのは，Master of Public
HealthandTropicalMedicine（MPH＆TM），M．S．P．H．，

M．S．，Ph．D．，それに寄生虫学におけるSc．D．などである。当学部ではいまや熱帯医学研修課程（Tropical Medicine
Training Programs）に焦点を当てているのであって，熱37

帯病（tropicaldiseases）におけるepidemiologyの開設を計画している。特に熱帯医学の医学生に，EnglishまたはSpanishでpublichealthの実習（practicaltraining）を行う。これにぱ3American Society of Tropical Medicine
and HygieneからcertiHcationが与えられることになっている。寄生虫学における基礎科学コース（Basic Science
Graduate

CoursesinParasitology）では，古典的寄生虫

学と分子，および細胞生物学と合体したようなものを教える。教育に関しては，tropical healthと医学的に重要な寄生虫の1aboratory

diagnosisの課程の増設を目指している。

いずれにしても，熱帯医学が生き残るには，継続的な学生の確保，および継続的な研究費の確保が大切である。それには，賢明な教科課程や研究課題の設定，熱帯地域途上国の研究機関との継続的連携』他の多くの医学分野との連携が必要であろう。熱帯医学は，常に変化しつつあることを認識すべきである。

HowardD．Engers（WHOマラリア免疫学委員会役員，

府とともに，民間からのgrantによっている。政府関係機

関としては，NIH，一NSF，AID，US

ArmyR＆DCom．

mandsなどがある。多くの研究費（researchgrant）は3年契約なので，長期研究計画が立てにくい。研究成果が不可欠なので，多くの論文が出される。日本では政府からの基本的な予算があるので，長期研究計画を立てやすい。4）
一般社会的環境（sociologicalinnuence）についていえば，米国における外国からの留学生の多くは，最初は戸惑うが，やがて米国社会に溶けこみやすいようである。日本は単一民族なので，留学生は社会に溶けこみにくいようである。
国際情勢から，日本も熱帯地域に自衛隊を派遣するなど，
将来はもっと熱帯医学に興味を持つようになるだろう。
演者は，現在ケースウェスタンリザーブ大学医学部（正式名称はInstitute of Pathology，Intrenational HealthInstitute，Case Westem Reserve University，School of
Medicine，Cleveland）に在職しているが，熱帯医学教育について，国際的な立場で見ると，我が国と西洋諸国とでは，現在までのところ，かなり状況や立場が異なるようである。

スイス）：

WHO・TDR（正式名称はUNDP／World
SpecialProgrammeforResearchandBank／WHO

Training

inTropi・

cal Diseases：TDR）は，1975年に設立された。次の2つの目的がある。1）途上国で実現し得る熱帯病の診断，治療，予防の方策の開発，および2）医学生物学および社会科学のトレー一ニングと，研究機関の協力のもとに，医学上の新しい技術開発の研究の強化である。必要性と指導性の長崎大学熱帯医学研究所における熱帯医学教育として，受講対象者がクラス，あるいはグループ形式で行われているものには，次の2つがある。文部省特別事業費による熱帯医学研修課程と，JICAの委託事業の，外国人集団研究コースである。熱帯医学研修課程は，毎年3カ月間，受講
定員は約10名，対象者は原則として，医師および生物系の学士であるが，現在では検査技師，看護婦，保健婦等も採

相川正道（ケースウェスタンリザーブ大学医学部教授，ア

用されている。第15回のコースが，平成5年6月に開始される。将来，西欧の熱帯医学研究所のように，近隣諸国からの研修生の参加の道を開くことができれば，さらに盛況を呈することであろう。外国人集団研究コースは，毎年9カ月問，受講定員は約9名，対象者は途上国の医師，生物系の学士等である。第9回のコースが，平成5年1月に開始された。なお東京大学医科学研究所においても，熱帯医

メリカ）：学に関する研修課程が行われている。

2つが，指針である。WHO・TDRでは次の6大疾患を指定している。すなわち，マラリア，住血吸虫症，オンコセ
ルカ症を含む糸状虫症，トリパノソーマ症，リーシュマニ
ア症，癩である。研究費の確保からも，研究にしても教育にしても，国内および国際的協力が必要であると考える。

熱帯医学に関する研究と教育について，日米を比較して見たい。1）熱帯医学関連教育・研究施設（educational
system）についていえば，米国では主として私立の大学で行われ，schoolofpublichealthに併設されている。・だから，より自由な政策をとることができる。日本では国立大学が主で，熱帯医学研究所（これはただ1つだけであるが）および，個々の大学の個々の教室で研究，教育がなさ れている。ただし米国におけるよりも，安定した予算を得ることができる。2）政治，経済上の理由から，米国は歴史的に熱帯医学に関与してきた。熱帯医学に関する教育機関はschoolofpublichealthとして，米国内だけでなく外国からの学生も参加してきた。3）予算の面では，米国では政文

献1）長崎大学熱帯医学研究所（1992a）：熱研50年の歩み（長崎大学熱帯医学研究所創立50周年記念）
2）長崎大学熱帯医学研究所（1992b）：研究所案内
3）Institute of Tropical Medicine，Nagasaki University（1992）：The Proceedings of Intemational Symposium：
Present

Situation

Tropical
Amiversary
NagasakiandFutureProspects

Medicine

inofInstitutetheAdvancedofofInstitutionsofCountries（The50th
TropicalMedicine，

University），Trop．Med．，34（4），127−181

38

Sylnposiun report

EDUCATION AND TRAINING PROGRAM IN TROPICALMEDICINE IN ADVANCED COUNTRIESHIDEYO ITAKURA
Received January 15 1993/Accepted 18 January 1993

On the occasion of the 50th anniversary of theTropical Medicine, and supported by the Ministry ofInstitute of Tropical Medicine, Nagasaki University in

Education, Science and Culture, Japan.
The current and future topics of "tropical medicine"including present situation, problems, future prospects

1992, the international symposium entitled "Present
situation and future prospects of institutions of tropical

medicine in advanced countries" was held. The sympo‑
sium was organized by the Institute of Tropical Medi‑cine, Nagasaki University and the Japanese Society of

Institute of Tropical Medicine, Nagasaki University

and educational programs with special emphasis on
challenges for the future were discussed at the meeting.

J pn. J. Trop.

39

Med. Hyg., Vol. 21 No. 1, 1993, pp. 39 92

PROCEEDINGS OF XXXIV ANNUAL MEETINGS OF
JAPANESE SOCIETY OF TROPICAL MEDIClNE
25‑26 N**･ b･* 1992, N*g*･"kiPresident

Keizo Matsumoto(Professor, Department of Internal Medicine,
Institute of Tropical Medicine, Nagasaki University)

CONTENTS
Prize Winner's lecture
JSTM (Japanese Society of Tropical Medicine) Young Investigator Award)
Ultrasonographic and serologic parameters of hepatic fibrosis

in Schistosoma japonicum infection H. Ohmae

Special lecture
The role of biofilm formation in the pathogenicity of Pseudomonas pseudomallei and otherrespiratory pathogens J. W. Costerton

Symposium: I Acute respiratory infection

Chaired by Y. Numazaki

1 Grobal strategy for control of acute respiratory infections J. Tulloch

2 ARI in the Western Pacific Region A. Shimouchi

3 Acute respiratory infections‑ in children in the Philippines M.G. Lucero
4 The importance and control of ARI in child population in China Z. Zhu

5 ARI in Thailand and Japan T. Nagatake

Symposium: 11 The status and scope of malariology

Chaired by M. Aikawa and H. Kanbara
1 Epidemiology of malaria: cases in North Sumatra, Indonesia and Solomon Island
A. Ishii

2 A primate model for human cerebral malaria: effects of artesunate M. Aikawa et al.
3 Diaguosis of malaria ‑review of new methods studied by Japanese researchers‑
M. Suzuki
Y. Midorikawa
4 Present drug invention for treatment of malaria

H. Ohtomo

5 Chemotherapy of malaria

M. Tsuji

6 Multifactorial characteristics of anti‑sporozoite immunity 'General presentation:
1 Serodiagnosis for disseminated gonococcal infection

E. Kita
2 Study on the isolation of frequency methicillin‑resistant Staphylococcus aureus in hospitals

in Guangzhou, China Z.K. Xing et al.

3 Causative organisms and clinical background of respiratory infections in Mae Sot area,

Thailand H. Masaki et al.

4 A case of borderline tuberculoid leprosy well responded to the chemotherapy

A. Hosokawa et al

5 A simplified procedure to increase the specificity of immunofiuorescens assay for Lyme

6 Study of Leptospira antibody among dogs in Okinawa, Japan Y. Yonahara et al.
7 Epidemiology of Japanese encephalitis in Japan with emphasis on the effect of vaccination
I. Ebisawa
8 Health consultation of Japanese staying oversea's developing countries K. Fujita et al.

40

9 Feature of infectious diseases in boat people in Omura Immigration Center
S. Kobayashi et al.
10 Resistance cif mice immunized with individual rabies virus internal structural proteins tolethal infection K. Mifune

11 Detection of dengue virus genome in dengue hemorrhagic fever (DHF) and dengue fever(DF) patients by using polymerase chain reaction (PCR) K. Morita et al.
12 Distribution of malarial parasite among febrile cases in south‑eastern part of Banglade‑

13 Occurence of malaria in passenger of a British ship K. Kawakami et al.
14 Malaria and glucose‑6‑phosphatase dehydrogenase deficiency in Solomon Island
A. Ishii et al.

15 DNA diagnosis of malaria using PCR techniques K. Kunisada et al.
16 Complex 11 (succinate‑ubiquinone oxidoreductase: fumarate reductase) in the respiratory

chain of Plasmodium mitochondria K. Kita et al.

17 Isolation and purification of dihydrofolate reductase of Plasmodium falciparum usingsynthetic DHFR gene G. Sano and T. Horii

18 An antimalarial activity of dilazep and dipyridamole Y. Ito and M. Aikawa
19 Ovale malaria‑like morphological changes of the parasitized red cells in tertian malaria

H. Amano et al.
20 Antibodies inhibiting the attachment of Plasmodium falciparum infected erythrocytes totarget cells S. Nakazawa et al.

21 Neuropathological findings of brains of malaria tropica M. Yamashita
22 Deep vascular schizogony in intradermal capillaries in foot pad of Plasmodium coatneyi
infected rhesus monkey ‑intradermal method for monitoring cerebral malaria‑
S. Kano et al.

23 Role of y/(

T cells in protective immunity against malaria

M. Tsuji et al.
24 Basic studies on the Mongolian gerbil as a susceptible host to filarial infection (10): Umbilicalscent gland
M. Mwanatambwe et al.
25 Basic studies on the Mongolian gerbil as a susceptible host to filarial infection (1D: Skin
sensitivities to chemical mediators

M. Shimizu et al.

26 Basic studies on the Mongolian gerbil as a susceptible host to filarial infection (12): Sensitiv‑

ity to EMC virus M variant
27 Bancroftian filariasis in Kenya

K. Shichinohe et al.

Y. Fujimaki et al.
28 Development of the new type vaccine against the filarial infection 1. Evasive mechanism offilaria from host immune surveillance
K. Fujita et al.
29 Development of the new type vaccine against the filarial infection 2. Transmission bloking

vaccineS. Tsukidate et al.
30 Medical examinations of children in Kingdom of Tonga
Y. Okuwaki et al.
31 A case study of international technical cooperation in the field of tropical infectious
diseases in northeast Brazil

S. Tateno et al.

32 Rotavirus epidemiology in Zambia

H. Oshitani et al.

33 Prevalence of enteric viruses in children in Karachi, Pakistan
S. Isomura et al.
34 Establishment of strategy for the prevension of post‑transfusion hepatitis B in Kenya

M. Koga et al.

35 Food habit of the poisonous snake young Habu, Trimeresurus favoviridis on the Amami

and Tokunoshima Islands H. Suzuki and E. Nakamoto

36 The reproductive cycle of the female Habu F. Yokoyama and H. Yoshida
37 An epidemiological study on the snakebites in Guangxi Zhuang Autbnomous Region, China

38 Effectiveness of protease inhibitor in severe Mamushi bite H. Watanabe et al.
39 The box jellyfish ( Chiropsalmus quadrigatus) stings in Okinawa Y. Araki et al.

41

40

Integrated control of Japanese encephalitis vectors ‑an inquiry with a mathematical41

A role of midgut in the susceptibility of mosquitoes to chikungunya virus
H. Yamanishi et al.

42

43
44

Host preference of Anopheres minimus Y. Tsuda et al.

Occurrence of vector mosquitoes of Japanese encephalitis in northern Thailand in relationtothe rice cultivation M. Takagi et al.
Effect of thermal acclimation on blood pressure and growth in spontaneously hypertensive
rate (SHR) ‑report II‑ K. Tsuchiya and M. Kosaka

45

Inhibition of IL‑1 secretion and proliferation of macrophage due to heat load
J‑M. Lee et al.

46

49

Analysis of micro‑environment on sweat skin covered by clothing material
K. Otomasu et alStudy on mechanisms of heat acclimatization due to thermal sweating M. Kosaka et al.
Cold tolerance of hypothermic syrian hamster due to acute cold exposure
N. Ohwatari et al.
A survey of intestinal parasitic infection in Kok Trap Commune, Cambosia; using the agar

50

An epidemiological study on Strongyloides infection on Miyako Island, Okinawa Prefec‑

47
48plate method K. Koga et al.

ture, Iooking for any possible relation between infection and farming activity
R. Asato et al.
51

Effects of flubendazole and mebendazole at a low dose on the growth of Angiostrongylus

52

Anticestode effects of gastrografin T. Matsumura et al.

53

Anti‑PHEX antibody, as a screening method for subclinical amebiasis

54

E. Okuzawa et al
Immunodiagnosis of human cysticercosis II. Results of the immediate type of skin test

55

Collagen synthetic activity in the fibrotic liver of Schistosoma mansoni‑infected mice56

M. Tanabe et al.
Necrosis of primary hepatocytes around Schistosoma japonicum eggs in vitro

cantonensis in rats J. Maki and S. Kanda

T. Amano
57
58
59
60
61
62

63
64
65
66

Relation between annual rainfall and number of Bulinus globosus, host snail of Schistosoma
S. Habe et al.
haematobium in Kwale, Kenya
Association of Qpisthorchis viverrini infection and hepatobiliary diseases in northeast
M. Itoh et al.
ThailandY. Hashiguchi et al.
Leishmaniasis and its transmission mode in Ecuador
Trials of low and high concentrations of topical paromomycin ointment for cutaneous
S. Nonaka et al.
leishmaniasis
Accelerated transformation of Tmpanosoma cruzi from trypomastigote to amastigote in a
M.R.A. Silva‑Tahat et al.
low pH medium
Y. Kaneda et al.
Gene encoding cysteine proteinase from Ttypanosoma rangell
M. Inoue et al.
Search for the proteins that have high affinity to HIV‑1 Nef
S. Mitarai et al.
A molecular analysis of the V3 gene of HIV‑1 isolated in Uganda
A mechanism of inhibition of natural killer cell activity leading to AIDS opportunistic
T. Kiyohara et al.
inf ection

Treatment of oropharyngeal candidiasis and cryptococcal meningitis in Human
Immunodeficiency Virus (HIV) ‑seropositive patients in Uganda

K. Oishi et al.

42Prize winner's lecture

JSTM (Japanese Society of Tropical Medicine)

Young Investigator AwardULTRASONOGRAPHIC AND SEROLOGIC PABAMETERS OF HEPATIC FIBROSISIN SCHISTOSOMA JAPONICUM INFECTIONHIROSHI OHMAE
Nagoya Kyoritsu Hospital and Department of Internal Medicine,
Nagoya University School of Medicine

We descrided the parameters useful in evaluating
the development of hepatic fibrosis in Schistosoma

and biochemical serum indicators of liver damage, theserum levels TBA and P‑III‑P strongly correlated withjaponicum infection, as well as its improvement after
treatment with praziquantel (PZQ). Various serologic

the development of hepatic fibrosis and portal hyperten‑

parameters and ultrasonographic images wereThese patients were subsequently treated with PZQ(3 x 20 mg/kg) , and 52 patients were followed up every

examined, and their changes were monitored using rab‑
bits infected with 200 or 300 cercariae of S. japonicum.

Infected rabbits were administered one oral treatment
of PZQ at a dosage of 100 mglkg at 6, 12, or 24 weeks
after infection. Histopathologic examinations revealedsion.

three months for a period of 17 months. Improvement in
the thickening of the portal vein wall and the intensityof the echogenic bands was detected 6 months after
treatment with PZQ. The level of splenomegaly wasthat PZQ has a strong effect, even on damage that

also reduced in 42 patients who originally did not show

developed long after the infection. The improvement ofmoderate hepatic fibrosis that developed over 24 weeks
after infection was also detected by histopathologic
examinations. The serum level of total bile acid (TBA)

the production of collateral vessels. A siguificant
decrease in the serum TBA Ievel was detected in all thepatients 6 months after PZQ treatment. However,significant ultrasonographic changes could not be detect‑

was the most sensitive parameter in evaluating theed in the patients classified as type 3, with severe hepatic

severity of hepatic fibrosis and its improvement after
treatment with PZQ. The level of serum procollagen‑III‑peptide (P‑III‑P) was also useful in evaluating thedevelopment of hepatic fibrosis, but not in its improve‑

fibrosis caused by the long‑term infection. These results

ment. Ultrasonography revealed specific echogenic

bands and nodules according to the progress of
granuloma formation and fibrosis, and the reversal ofthese changes could be observed after treatment withPZQ .

An ultrasonographic examination concomitant withhematologic and biochemical serum analyses was per‑fomed on 102 patients at the Schistosomiasis Hospital in

Leyte, the Philippines. The ultrasonographic liver
images were classified into 4 patterns, according to theperiportal fibrosis and the patterns of echogenic band.
Eleven cases with a long‑term infection showed typicalseptal formation (network pattern) . Other ultrasono‑graphic changes in the portal system, such as the sever‑
ity of splenomegaly, did not correlate with the age of thestudy patients or the duration of their infection; how‑ever, the production of collateral vessels was clear in thegroup of older patients. Among various hematologic

clearly show that ultrasonographic examination, alongwith data on the serum TBA Ievel, provides a sensitive
tool to monitor the severity of hepatic fibrosis and portal

hypertention caused by S. japonicum infection, as wellas the improvement resulting from PZQ treatment.

43

Special lecture

THE ROLE OF BIOFILM FORMATION IN THE PATHOGENICITY OF
PSEUD OMONA S PSEUDOMALLEI AND OTHER RESPIRATORY PATHOGENS
J. WILLIAM COSTERTONNSERC Professor of Microbiology, University of Calgary,

Cargary, Alberta, Canada
In nature, bacteria grow in two distinctly different
modes of growth; planktonic cells float or swim in fluid

menstrua, while sessile cells form slime‑enclosed
biofilms on available surfaces. Recent work in manylaboratories has shown that cells in these different
modes of growth differ very radically in their structure
and physiology, but, most importantly, in their suscepti‑

bility to host defence mechanisms and to antimicrobial
agents. Biofilm bacteria are protected to a very large
extent from antibodies, surfactants, phagocyiic whiteblood cells, bacteriophage, biocides, antibiotics, andtime, and then flare up to produce overt symptoms.
These acute exacerbations often respond to antibiotic
chemotherapy, because their causative agents are plan‑ktonic, but the protected biofilm niduses are not affectedby these agents and these chronic infections commonly
recur, following treatment with agents that show excel‑
lent efficacy against test tube‑grown planktonic cells inin vitro sensitivity tests.

An unequivocal understanding of the formation of
biofilms by bacteria is of great importance in under‑
standing the process whereby bacteria can occasionally

adverse environmental conditions such as acidity or
drying. The direct examination of bacterial pathogens
growing in the human lung (Legionella. Ps. pseudomallei

establish highly refractory infections of this often‑chal‑and Pseudomonas aeruginosa in cystic'fibrosis) or in thement.‑

lungs of domestic animals (Pasteurella haemolytica inbovine shipping fever) clearly shows that these cells
grow in slime‑enclosed microcolonies functionally iden‑
tical with biofilms.

In controlled animal infection experiments, cells of

all four of these bacterial pathogens have been shown tobe effectively cleared within four hours when they wereadministered as free‑floating planktonic cells in concen‑
trations between I x 106 and I x 104, depending on thepathogen in question. However, chronic and occasional
acute infections always developed when we administer‑
ed between I x 103 and I x 102 cells of the same strains in

the form of slime‑enclosed mini‑microcolonies directly
into the lung by aspiration. These data indicated thatthe biofilm mode of growth of pulmonary pathogens
may be pivotal in their ability to establish and maintaincolonization in lungs that are defended by specificdefence mechanisms such as surfactants, antibodies, andactivated phagocytes.
Once established in large microcolonies within thelung, these pathogens can exert pathogenic effects by
the release of toxins and by the stimulation of antibody
responses that fail to eradicate these organisms, andthey may also release planktonic cells from their well‑defended microcolonies and thus initiate acute pulmo‑nary infections. It is characteristic of these biofilm
infections that they remain indolent for long periods oflenged but seldom‑infected organ that serves as our
respiratory interface with the gas phase of our environ‑44

SympoSium
I . Acute RespiratOry Infection

1 GLOBAL STRATEGY FOR CONTROL OF ACUTE RESPIRATORY INFECTIONS
J. TULLOCH
Division of Diarrhoeal and Acute Respiratory Disease Control,

World Health Organization, Geneva, Switzerland

Acute respiratory infections (ARD are now theleading cause of death in children less than five years ofage in developing countries. In 1990 they accounted for
4.3 million deaths, approximately 12,000 per day. They

represented 33% of a total of 12.9 million deaths inchildren. Most of these deaths were due to pneumonia,
a large proportion of which is due to bacterial infectionthat can be effectively treated with antibiotics.

lin are the best choice for treatment of pneumonia, nonsevere, at home. Essential antibiotics for treatment ofsevere pneumonia at small hospitals are benzylpenicil‑
lin, gentamicin and chloramphenicol.
The protocol was tested in intervention studies inrural areas of eight developing countries; the reductionin the mortality associated with acute lower respiratory
infections ranged from 25% to 67%. The protocol is the

The annual incidence of pneumonia in children

core of the WHO guidelines on standard case manage‑

under 5 years of age in developing countries varies fromment of ARI in children. Special instructions are given
for infants less than 2 months old because the clinicallO to 20 percent, that is 3 to 5 times higher than indeveloped countries. The higher incidence of pneumonia
in developing countries is explained, at least to somepresentation, the etiology and the treatment are
different from those for older children.

extent, by the presence of important risk factors such as

A series of technical review papers has been issued

malnutrition, Iow birth weight and nasopharyngeal car‑by the WHO Programme providing the scientific bases

riage of pathogenic bacteria which are much more

for the WHO's recommendations. A wide range ofprevalent than in developed countries. There are otherrisk factors which may also contribute to the burden ofchildhood pneumonia in developing countries like theprevalence of indoor air pollution from biomass fuel,exposure to chilling in young infants and overcrowding.

training courses have been developed, or are under

The World Health Organization, in consultation
with international experts, has developed a simple
protocol for the detection of pneumonia based on reli‑able clinical signs and classification of the disease bydegree of severity. The key signs to recognize pneumo‑
nia in children are fast breathing and lower chest indr‑awing. Fast breathing is more sensitive than the pres‑ence of rales upon auscultation to detect pneumonia inchildren. In addition fast breathing is an objective sign

which can be taught to paramedical staff, and evencommunity health workers, who can recognize pneumo‑

preparation. They include training on managerial skills

for programme managers and supervisors, and clinicaltraining for doctors, paramedical staff and community
health workers. A focussed ethnographic study protocol
is available to collect information on the mothers per‑ceptions and practices relating to pneumonia and other
ARI in children which is essential for the local adapta‑
tion of communication messages. Guides for evaluation
surveys at health facilities and at households are being
completed. A manual for the surveillance of bacterial
drug resistance is being field tested in four countries.

The number of countries with national control
programmes was 63 at the end of 1991. WHO is provid‑
ing technical assistance in planning, managerial andclinical training, communication, monitoring and evalu‑

nia in a child in the absence of doctors. Pneumonia is anation. WHO maintains close collaboration withacute disease which, if untreated, may kill the young

UNICEF in the support to the national programmes.

child in a very few days, or lead to prolonged or compli‑
cated infections.

The WHO ARI Programme also has an active
research programme focused on clinical and behavioural

Streptococcus pneumoniae and Haemophilus

aspects of managing ARI in developing countries. A

influenzae are the most common bacterial agents ofcommunity acquired pneumonia in children. Standard

review is being conducted of the feasibility and cost‑effectiveness of strategies to prevent pneumonia in

antimicrobial treatment should therefore be effective
against these two bacteria. Cotrimoxazole or amoxycil‑

children in developing countries.

45

2 ARI IN THE WESTERN PACIFIC REGIONAKIRA SHIMOUCHI
Department of Preventive Medicine, Kyoto Prefectural University of Medicine

Acute respiratory infections, especially pneumonia,

are a leading cause of mortality in children under 5
years of age and responsible for some 450,000 deaths
annually in this age group in developing countries of theRegion. Two thirds, 300,000 deaths occur in China.
Main factors of high mortality are (1) poor nutritional
condition of children, (2) unavailability of proper casemanagement including proper antibiotics and (3) under‑

introducing prevention and control measures at thecommunity level. Main thrust of the programme is toimprove diagnostic skills of pneumonia and to rational‑
ize use of antibiotics. As of June 1992, national pro‑grammes have been established in 15 countries including
9 priority countries which infant mortality rate is morethan 30 per 1,000 Iive births. So far 30% of health staff

area where infant mortality is more than 30 per 1,000
live births, ARI account for more than 25% of infant

at primary health care level have been trained in thestandard case management. A Regional target is thatby 1995, 80% of the child population in the Region will
have access to appropriate care for ARI. To achievemortality.

this target eventually more than one million health staff

Malnutrition is especially prevalent in Cambodia,
Laos, Papua New Guinea, Philippines and Viet Nam. In
one survey in the rural area in the Philippines showedthat more than 70% of children weight less than 80% of
standard weight for age.
Mortality is generally higher in rural and remoteareas, where often more than half of deaths occur atneed
to be trained. ‑,Examples of the programme impact are; (1) u e ofhome without medical attendance. It is because

to face health education of mothers at health facilities inmothers/families do not recognize important signs ofsevere diseases in time and therefore tend to bringFiji. (3) Use of intravenous fiuids and chest X‑ray andpatients to health care workers too late.
Antibiotics are absolutely in shortage in rural areas

nia have been rationalized in the Philippines andutilization of health services. Generally speaking, in the

antibiotics have been reduced from 60% to 20% of ARI
after 3 years of training and regular supervision in Fiji.

(2) The proportion of pneumonia cases which havehistories of fast breathing/chest indrawing for 3 days ormore had reduced from 62% to 24% after 2 years of facechoice of antibiotics for inpatients with severe pneumo‑

and Viet Nam. In Papua New Guinea supply andVanuatu. (4) The reduction in mortality from pneumo‑
nia has been demonstrated in China.
Reviewing the effects of training programme, regu‑

distribution of drugs are often irregular, even budget forlar supervisory visits (for instance, one month, 6 months

drugs is fairly sufiicient. In those countries, the situation

and I year after the training) are found to be indispens‑worsens by misuse and overuse of antibiotics for coughand cold. The problem arising in this connection is anable to sustain the knowledge and skills which are

in Cambodia and Laos and relatively in the Philippines

increased bacterial resistance to antibiotics, particularly

in city areas where overuse of antibiotics is rampant.
In addition even at the first referral hospital (dis‑trict hospital leveD in some countries, proper antibiotics

are often not used and intravenous fluids are overused
and misused, which may result in a higher case fatality
rate yet with high costs.

The objective is to reduce morbidity and mortality

from ARI particularly pneumonia in children byobtained by training. Thus a good supervisory activity
is a key to a successful programme.
Future emphasis will be as follows; (1) strengtheningof health education and supervisory activity, (2) clinicaltraining at district hospital level, (3) undergraduate
training for medical and nursing students and students
for other health workers, (4) involvement of private
sectors by disseminating information and training and(5) securing supply and distribution of antibiotics espe‑

cially in Cambodia and Laos.

46

3 ACUTE RESPIRATORY INFECTIONS IN CHILDREN IN
THE PHILIPPINESMARILLA G. LUCERO
Research Institute for Tropical Medicine, the Philippines

Acute respiratory infections (ARD, specificallypneumonia, is a major killer of younchildren, not onlyin the Philippines but in other developing countries aswell. A program for the control of ARI was thus
developed by the World Health Organization in 1982.
This program was based on the following assumptions:
1 ) that high mortality from ARI was due to a highincidence of bacterial pneumonia, 2 ) that the principal

causes of c.ommunity‑acquired bacterial. pneumonia

were Streptococcus pneumoniae and Haemophilus
influenzae which were sensitive to cotrimoxazole, peni‑
cillin, amoxycillin and chloramphenicol, 3) that pneu‑
monia could be diagnosed and the severity of pneumonia

determined by quite simple means, 4 ) that mothers
could be trained to recognize the danger signs of pneu‑

monia and 5 ) that community health workers could betrained to diaguose and treat pneumonia correctly. The
Philippine Government in 1979 established the National

ARI or acute lower respiratory infection, specificallypneumonia, is 0.5 per child per year, considerably muchhigher than in developed countries where the incidence
is only 0.03 per child per year. Consequently, mortality
is also high. From a study in Bohol Island, we foundthat pneumonia was responsible for 27% of all deaths inl,818 children < 5 years during a six‑year period.
Risk factors for morbidity and mortality: young age =( <2 years),,‑ malnutrition, crowding in sleeping quarters,
and parental smoking were found to be risk factors for
ARI morbidity hospital‑based studies conducted in 1984
showed that pneumonia with complications, presence ofmeasles and malnutrition were significant predictors for
mortality among children admitted with severe pneumo‑nia. A case‑control study of all ARI deaths and theirrespective controls in Bohol from 1985 to 1991 showedthat births attended by traditional birth attendants,
presence of low birth weight, non‑breastfeeding, non‑

ARI Steering Committee (NASO with these specific

DPT immunization and low education of mother werefunctions: to correlate and interpret data obtained fromsignificant risk factors for mortality in children withpneumonia. A̲ study on the effect of breastfeeding andthe risk of getting pneumonia from 1989 to 1991 showeda significantly higher risk among infants who had notbeen breast fed.
Etiology: 537 children < 5 years of age with pneumonia

research projects and health services statistics, todevelop a national programme for the management andcontrol of ARI based on above data and to promote anddevelop research which is in direct support of the ARI

programme. The NASC adopted a program which was
directed towards the development of Primary HealthCare (PHO intervention. Research activities to evalu‑
ate the effectiveness and feasibility of these interven‑tions in terms of targets set to achieve "Health for All
by the Year 2000" were undertaken. It is in this context

that I present to you the studies that have been done at

the Research Institute for Tropical Medicine (RITM),
the research arm of the Department of Health, geared
towards the formulation of a national program for thecontrol of ARI with the main goal of reducing mortality

admitted at the RITM from 1985‑1987 were studied. S.
pneumoniae and H. influenzae were found in 42% of 72
bacteremic children. These organisms were sensitive tocotrimoxazoie and amoxycillin, antibiotics recommend‑

ed by WHO. for ARI case management. Yield forbacteria in blo'od cultures was low partly because ofprevious antibiotic therapy before admission.
Impact of ARI Control Program on childhood mortality:
the ARI control program was developed and implement‑
ed in 5 municipalities in the rural island of Bohol

due to ARI among children < 5 years of age in the(intervention area). Three municipalities did not

Philippines.

receive the intervention (non‑intervention area). After

Incidence: studies were undertaken to define morbidity

6 years of mortality monitoring, a statisticallyand mortality due to ARI and to determine the risk
factors for these. From a community‑based study insignificant reduction in mortality from all causes wasshown in both areas but the decline was more rapid in

Manila done from 1985‑1987, it was shown that Filipino
n urba n population suffer about 6.1 episodes

the intervention area (12% per year versus 6%). The
reduction in mortality due to prima,ry pneumonia wasof ARI per year. This is about the same incidence asother children worldwide. However the incidence ofalso higher in the intervention than in the intervention
area. This decline in mortality in the intervention area

chiJdren in47

was very steep during the last two years of the study
when intensive health education and supervisory activ‑

ities were taking place. This activities were very

health education as a component of the control program.
A separate study in an urban arezi showed that healthworkers in the area were able to comply or adhere to theminimal during the first four years and shows the impor‑tance lof supervision of health care workers for better

ARI case management program. Compliance rates orappropriateness of ARI case management improved

active case management and also the importance ofthrough time.

4 THE IMPORTANCE AND CONTROL OF ARI IN CHILD POPULATION
IN CHINAZONGHAN ZHUCapital Institute of Pediatrics, Beijing, China

During the last three decades the infant mortality
rates were siguificantly reduced from 250 per 1,000 in
1950s to 40.1 per 1,000 in 1990 in China. Besides eco‑nomic development and improvement of standard living,
there were three important factors of health develop‑

the first important disease causing death in infants andment related to the reduction of infant mortality

protectable diseases accounted for only less than 2%

young children is acute respiratory infection (ARD,
specially pneumonia. The death from pneumonia ac‑
counted for 23.9% of infant mortality and for 22.7% of

under 5 children's mortality. While, the vaccine‑

improvement of medical services, development of immu‑

under 5 children's mortality in China. Therefore, it isnization programmes and family planing. With thesuccessful implementation of the immunization pro‑definitely suggested that the first priority in reduction ofgrammes, the mortality rates from the vaccine protecta‑
ble diseases were reduced significantly.

trol pneumonia, which kills about 300,000 children per

The mortality rated from measles were reduced
from 39.8 per 100,000 in 1960 to 0.02 per 100,000 in 1987,

children's mortality, especially in rural areas is to con‑year in China each year. What we could do for the
300,000 children dead from pneumonia before the new
vaccines available to the etiological pathogens ?

similary, polio from 0.16 to 0.004, pertusis from 1.77 toCollaborated with WHO and UNICEF, the ARI

0.01, and diphtheria from 2.69 to 0.007. The mobidity

standard case management was developed andrated from those diseases were also reduced

introduced to the national programme of ARI control in
China, the purpose of which is to improve delivery ofsignificantly.

What is the situation of child health after basically

health care for the children with ARI. Three main

control of vaccine‑protectable diseases? In order toactivities were carried out in study areas, including

answer the question, we carried out several

development of ARI training materials and methods,

epidemiologic studies on child mortality in the areas

establishment of supervision systems in primary healthwith different social‑economic levels in China'in 1990‑

level and improvement of facilities of the first referral

1991. The data are shown as follows; the IMR and
USMR in developed areas, such as in Beijing, were 12.5

hospitals in rural areas. The data from a three‑year
study in three counties indicated more than 50% of

and 13.6 per 1,000 respectively, which were quitely close

reduction of infant and under 5 children mortality rates.

to that in developed countries, however, the IMR and
USMR in remote areas and poor areas were still veryhigh. (IMR 40.1‑68.0, USMR 49.4‑84.4 per 1,000) The

Encouraged by the results of the pilot study, the ARI

studies on death cause in infant mortality suggested thatstandard case management has been introduced andpractised in more than 400 counties since 1991, which
covere about 200 million population in China.

48

5 ARI IN THAILAND AND JAPANTSUYOSHI NAGATAKE
Department of Internal Medicine, Institute of Tropical Medicine,

N agasaki University

It is well recognized that the majority of acute
upper respiratory tract infiammations are caused byviral infections which are sometimes followed by bacte‑rial infections. This is generally supported clinically bychanges in the initially watery nasal discharge or
mucous sputum which become yellowish and prulent.
Bacterial infections cause complications of common
cold, such as acute sinusitis, otitis media, acute bror‑

chitis and pneumonia. Especially, it is sometimes dan‑gerous for small children and aged people to catch cold
because of various above mentioned complications due
to secondary bacterial infections.

are H. influenzae. S. pneumoniae and B. catarrhalis.

We examined the causative organisms of respira‑tory infections from 1989 to 1991 at Mae Sot General
Hospital in collaboration with Chiang Mai University,
Thailand.
We collected sputum from acute bronchitis or pneu‑
monia patients and identified causative organisms withquantitative sputum culture method and infiammatory
sputum cytology. The most frequently identified path‑ogens in respiratory infections at Mae Sot General
Hospital were H. influenzae. S. pneumoniae and B.
catarrhal is.

We have demonstrated in many articles that theMoreover, we examined the minimum inhibitory

most important five respiratory pathogenic bacteria areconcentrations of the representative penicillins, cephems

Haemophilus influenzae. Streptococcus pneumoniae.
Branhamella catarrhalis. Staphylococcus aureus andand other antibiotics against these pathogenic strains.

Pseudomonas aeruginosa. Especially in acute bronchitis
and pneumonia, the most important causative organisms

In this study, we compared the causative organisms ofbacterial respiratory infection between Thailand andJ apan.

49

II . The situation and scope of malariology
1

EPIDEMIOLOGY OF MALARIA: CASES OF NORTH SUMATRA,INDONESIA AND SOLOMON ISLANDSAKIRA ISHII
Department of Parasitology, National Institute of Health, Tokyo

Epidemiological studies of malaria is essential forthe effective control of malaria. We need baseline data
not only of parasitology and entomology but also othersociological data.
Spleen rate has been used as a useful primary index
of malaria endemicity. In North Sumatra, by the use of
palpation it was found mesoendemic state of malaria. In
Solomon Islands, we tried to use a portable ultrasonicmachine and found that children less than 15 years ofage showed very high positive rate of malaria when he/she has splenomegaly. It may be used as a screening
method for malaria since ultrasonic examination is
objective, easy and acceptable for children.

Blood examination is essential for parasite rate
figure, however, Iocal situation does not allow to use

ELISA with crude antigen of cultured P. falciparum. It

was found that if we examine students of secondary
school, we can obtain informations of malaria en‑
demicity of different villages from which they come.
ELISA can be performed in a large scale and provide
data of change in epidemiological state as a mass sayafter any interventions.

IIL our study in North Sumatra, malaria is notevenly distributed. At the very begining we attempted
to conduct stratified random sampling to assess malaria
endemicity. We selected two villages from three geo‑
graphical strata: mountain area, plain area and coastal
area. We found patchy distribution of malarious vil‑lages in coastal area facing Maracca Strait.

clinical diaguosis is a common practice in most clinics

Another important finding in North Sumatra wasthat gametocyte carriers werer mostly in younger age
group especially children under 15. And high density

and health centers. This prevents to provide

gametocyte carriers were in age group less than ten. We

scientifically sound statistics of malaria epidemiology.

attempted to detect malaria in lower grade primaryschool children and pre‑school children. We used not
only chloroquine and Fansidar but we added also prima‑quine in the hope to interrupt transmission. We could
obtain drastical reduction of especially falciparum
malaria which lasted fairly long period more than one
year. One problem we encountered was G6PD deficiency
in red blood cell in inhabitants of North Sumatra andSolomon Islands. We detecte
4‑5% deficient rate inNorth Sumatra and rather high Tate of deficiency 8‑14%
in Solomon Islands by Fujii's method which is simple,

microscope and Giemsa staining procedures. Instead

Occasional blood collection by staff of local healthcenter was not enough to estimate malaria situation in
North Sumatra. We found enough training of micros‑
copists is very important to have correct data of para‑site rate in Solomon Islands. We have been trying to
examine the usefulness of fiuorescent staining withAcridine Orange on ordinary light microscope using
interference filters. This can be used in villages byutilizing even direct sun light. It is said this method issuitable to detect low grade parasitaemia.
We have been trying also to develop DNA diaguosis

of malaria parasites by the use of. PCR (polymerase
chain reaction) . Double PCR method is found to be

more sensitive than microscopic examination for
confirmation of malaria infection although it takes
about 10 hours. Other methods of DNA detection suchas ED‑PCR (enzymatic detection) and enzymatic dem‑easy and applicable in the field. We must introduce thismethod before to use primaquine.
We hope these methods we tried in North Sumatra
and Solomon Islands could be applicable in malarious
rural villages as one of primary health care approachsystem.

Recent development of mathematical model of

onstration of hybridization have been tried with promis‑
ing results. These may be used as epidemiological tools

malaria transmission made it possible to use computor
simulation study in the epidemiology of malaria. We

in future.

would be able to forecast the results of any intervention

Seroepidemiological studies have been carried out

in both North Sumatra and Solomon Islands. We usedof malaria transmission in future.

50

2 A PRIMATE MODEL FOR HUMAN CEREBRAL MALARIA:
EFECTS OF ARTESUNATEMASAMICHI AIKAWAl, DAHLEM SMITH1, ARTHUR BROWN2, YOSHIMASA MAENO1,
TATSUYA TEOOSH11, TETSUHIKO TOYOSHIMA1, KYLE WEBSTER3
AND WILLIAM E. C,OLLlNS3
Case Western Reserve University, Cleavland

Armed Forced Research Institute of Medical Sciences, Bangkok'
and Centers for Disease Control, Atlanta'

Although several animal models for human cerebral
malaria have been proposed, none have shown pathologi‑
cal findings that are similar to those seen in humans. In

order to develop an animal model for human cerebral
malaria, we studied brains of rhesus monkeys infectedwith a primate malaria parasite, Piasmodium coatneyi.

Our study demonstrated PRBC sequestration andcytoadherence of knobs on PRBC to endothelial cells in
the cerebral microvessels of these monkeys. Cerebral

microvessels with sequestered PRBC were shown by
immunohistochemical analysis to possess CD36, TSP,
ICAM‑1, VCAM‑1 and ELAM‑1. These proteins wereof monkeys which were treated with one dose ofartesunate and Group IV were controls. Parasitemia ofthese‑monkeys ranged from 13.6 to 19.5% before treat‑

ment. Twenty‑four hours ofter treatment, the par‑asitemia was reduced to 2.2% in Group I, 0.1% in GroupII and 10.6% in Group IV. The rate of sequestration
which was 30% before treatment became 0.1% in GroupI and 11 and 2% in Group 111. These data clearly indicatethat artesunate not only reduced parasitemia, but also
reduced PRBC sequenstration in cerebral microvessels.

ELAM‑1 became negative in Group I after the treat‑ment with artesunate, although the presence of othernot evident in the cerebral microvessels of uninfected

cytoadherence proteins in cerebral vessels was not alter‑monkeys. After establishing that rhesus monkeys in‑ed. In summary, this is the first in vivo study to showthat artesunate reverses PRBC sequestration in cerebral
microvessels in cerebral malaria. By using this animal

fected with P. coatneyi can be used as a primate model
to study human cerebral malaria, we investigated effects

of artesunate on this model. Eleven rhesus monkeys
were divided into 4 groups; Group I consisted of mon‑keys which were splenectomized and were treated with
3 doses (200 mg/kg) of artesunate, Group 111 consistedmodel, we may be able to evaluate strategies for thedevelopment of antimalarials and vaccines to cure and/or prevent cerebral malaria.

3 DIAGNOSIS OF MALARIA‑REVIEW OF NEW METHODS STUDIED BY JAPANESE RESEARCHERS‑MAMORU SUZUKI
Department of Parasitology, Gunma University School of Medicine

Microscopic examination on Giemsa stained blood
specimen makes the standard method to give definite

ber of parasites in the blood specimen (Wataya,

diaguositic answer to a suspected patient. A new tech‑

Okayama Univ.). Supplemental diagnosis trial by im‑

acridine organge fluorescence dye is being evaluated inmunological test is applicable to highly suspected cases
in whom parasites are not detected by the blood exami‑
nation. Indirect fiuorescent antibody test leads to evenmany researchers. The rapid and simple techniquespecies identification of causative agent in "virgin infec‑

seems of considerable applicable value both in the labo‑tron" so far (Kano Gunma Univ.). Within one year

ratories and also in the field. The method seems to be
applicable in endemic countries of poor facilities. DNA
hybridization technique using probes of Plasmodia has
become sensitive enough to catch extremely small num‑since the onset of the disease, retrospective malarianique developed by Kawamoto (Nagoya Univ.) using

diaguosis for radically cured patients is feasible by thistechnique. The results are useful to decide primaquine
administration to the patients with past vivax and ovale

51

infections to prevent relapse. Cerebral malaria is athreatening complication associated with falciparum
malaria. Diagnostic measure to predict cerebral compli‑
cation is required. Recent reports of animal models for

priate DNA probe from P. falciparum (Waki, Gunma
Univ.). Ultrasonographic examination of liver andspleen was attempted with schistosomiasis cases in
Leyte (Ohmae, Univ. Tsukuba) The method would behuman cerebral malaria looks to be promising inapplicable in measuring spleen rate in malaria pro‑promoting the study. In vitro drug ‑resistant test isneeded to select effective drugs to falciparum malaria

gramme. Every diagnositc tool raised above can also be
used in the field survey. However, Iocal conditions,

before ･ insitituting an anti‑malarial administration.
Counting parasites at schizont stage in the culture withsidered in selecting any technique for practical use in thevarying concentrations of a tested drug makes mostmalarious areas which often can least afford to provide

crucial part of the test procedure. The counting can belaboratory facilities.

feasibilities, cost‑effectiveness should be carefully con‑repleced by DNA hybridation technique using an appro‑

4 PRESENT DRUG INVENTION FOR TRAETMENT OF MALARIAYUTAKA MIDORIKAWA
Department of Public Health, Mie University School of Medicine

Malaria is endemic or sporadic through out most of
the tropics and subtropics. One hundred million peoples
are infected annually and 1% of them die. The incid.enceof the disease is increasing to different countries by

proved that DSG showed antimicrobial activity on somebacterial strains. To find out a new and effective anti‑

malarial drug, deoxyspergualine (DSG), an im‑
munosuppresive agent and a polyamine inhibitor, wasincreasing the chance of travelling throughout theworld. The incidence of the resistance to popular
antimalarial drugs for example chloroquine is also

tested on Plasmodium berghei mouse model. DSG atincreasing throughout the world. By this reason, a new
type of effective antimalarial drug is desired to bediscovered.
Polyamines play an important roles in the prolifera‑tion of cellular DNA, RNA and protein synthesis as well

DSG was proved by decreased the percentage of par‑as the cell proliferation. In present study, we investigate

the effects of polyamine inhibitor on malarial parasite.

Deoxyspergualin (DSG), a potent immunosuppres‑sive agent, was proved as a polyamine inhibitor. We

dose of 5 mg/kg b.w. and 2.5 mg/kg b.w. was injectedin mice that infected with P. berghei. The effectivity ofasitemia and spleen weight and prolonged the survival
days of infected mice.

Not only P. berghei, but also P. falciparum wasshown an anti‑malarial effect on the malarial parasite
of in vitro culture by DSG.

These findings show that DSG will be one of thecandidate for anti‑malarial drug.

5 CHEMOTHERAPY OF MALARIAHIROSHI OHTOMO
Department of Parasitology, Jikei University School of Medicine

Historically, preparations from cinchona bark had
been used widely in Europe as a specific malaria remedy

extensively used as the drug of the first choice for thefrom early 17 centry. Antimalarial chemotherapy was

suppressive treatment of all species of malaria.
After 1960, however, the development resistance of

rapidly developed in this century; till 1950 the discovery

Plasmodium falciparum to chloroquine and otherof antimalarial agents such as chloroquine, proguanil,
pyrimethamine, sulfonamides, sulfones and primaquine.
Chloroquine, the most successful schizontocide, has beenschizontocides has been detected in many areas of thetropics and become the chief obstacle to the modern
chemotherapy of malaria. Thus, to guarantee protec‑

52tion against falciparum malaria, the organization

tives or halofantoline. In addition, the development ofrelated vyHO recentry declared that a variety of investi‑

resistance of Plasmodium falciparum to Fansidar, andmost recentry also mefioquine, was reported. However,gations concerning the development of novel drugs
based on the usage of medicine and drug‑combination
therapy, the establishment of pharmacokinetics inpatients, the development of evaluation methods on drug
resistance, and medical care based on pathophysiology
should have priority.

On recent progress in the chemotherapy of falcipar‑

um malaria, pyrimethamine combined sulfadoxicine(Fansidar) was recommended after early 1970's andmefloquine from 1980'. In some areas, serious cases ofthe falciparum malaria were given artemisinine deriva‑

quinine, new understanding of the effect, and in combina‑

tion with tetracycline still work well for the above
mentioned resistant malarial parasite. The effect ofparenteral administration of quinine or its isomer,
quinidine on the severe malaria has lately attention.
Finally, we expect that currentry investigated agents
such as pyridinemethanol, triazine, piperaquine andacridine compounds, also pyronacridine developed in
China are completed as superior anitimalarial agents.

6 MULTIFACTORIAL CHARACTERISTICS OF
ANTI‑SPOROZOITE IMMUNITY
MORIYA TSUJI
Department of Medical and Molecular Parasitology,

New York University School of Medicine

Protective immunity against rodent, simian andhuman malaria sporozoites can be achieved by immuni‑
zation with irradiated sporozoites. A number of experi‑mental findings have provided clear evidence indicatingthat antibodies and T cells play a major role in mediat‑ing this anti‑malaria immunity.
The protective antibody response has been shown tobe directed mostly against the CS protein, Iocated on the
sporozoite surface. This protection against sporozoites

can be achieved by a) passive transfer of monoclonal
antibodies against the repeat domain of the CS protein
and b) immunization of mice with synthetic peptides,
designed to induce anti‑CS protein antibodies.

To enhance the induction of antibodies, the use of
potent adjuvants and the modification of the molecular
structure of the synthetic peptides, as immunogens, havebeen performed. Of those improvements, multiple

rodent malaria systems, Plasmodium berghei and P.
yoelii. It has been shown that protection induced bysporozoites can be abrogated by depleting the immune
mice of their CD8+ T cells. More importantly, recent
studies have shown that CD8+ T cell clones directedagainst a defined cytotoxic epitope of the CS protein
conferred protection against malaria, when passivelytransferred to naive mice.
As for CD4+ T cells, while they have been known toplay a helper role in the induction of protective anti‑
sporozoite antibodies; there has, until recently, been no
evidence indicating that CD4+ T cells may also inhibit

the development of malaria liver stages. Our recent
studies demonstrated that adoptive transfer of CD4+ T
cell clone into mice confers protection against a spor‑
ozoite challenge. The antigen recognized by this T cellclone is shared by sporozoites and blood forms of P.

antigen peptide (MAP), which is chemically definedberghei, and differs from the CS protein. The studies ofsynthetic polymers containing B and T helper epitopes
against the CS protein, has been shown to induce highlevels of anti‑CS antibodies and confer protection

another group also showed the protective activity of
CD4+ T cell clones, which recognize the CS protein.
Thus considerable knowledge have been gained, inagainst viable sporozoites.

recent years, regarding the multifactorial characteris‑

The presence of T cell‑mediated mechanisms intics of anti‑sporozoite immune mechanisms. The

anti‑sporozoite immunity has been suggested by earlier
studies indicating that p ‑suppressed mice can mount aapproach of dissecting every components of this immune
mechanisms, one by one, will certainly help us to unveil

protective immunity after sporozoite immunization.

the complexity of anti‑sporozoite immunity.

Among T cells, the anti‑parasite role of cytotoxic CD8+

The fact that sporozoite‑induced immunity seems

T cells has been clearly demonstrated in two of theto be multifactorial should not be seen as yet another53

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in54

Genaral presentation

1 SEROLOGICAL DIAGNOSIS OF DISSEMINATED GONOCOCCALINFECTION
EIJI KITA
Department of Bacteriology, Nara Medical University

The present study was addressed to evaluate theefiicacy of serodiagnosis for disseminated gonococcal

DGI was 42 (12 males, 30 females) . All of these patients

infection (DGD. Serodiagnosis was done using the

Serological test, either PHA or ELISA disclosedthat all the patients were positive with the antibody
responding to G‑Ag 6.8 antigen nd also that antibody

purified gonococcal antigen (G‑Ag 6.8) which had been

determined to be associated with cytoplasmic mem‑branes, and carried out by both the passive hemagg‑
lutination test (PHA) and enzyme‑1inked immunoadsor‑
bent assay (ELISA) . Cut‑off titers of these two tests
were 4 (log, titer) for PHA and 30 corrected untis(Ecm) for ELISA, and these tests detected predominant‑ly lgG antibody to G‑Ag 6.8 antigen used in this study.
A total number of subjects with a tentative diagnosis of2

had a past history of urogenital gonococcal infection.

titers in their sera fell rapidly after the effective chemo‑

therapy. Isolation of N. gonorrhoeae was done frorn the

blood or purulent specimens obtained from the skinlesion. Bacterial culture was positive with 22 out of 25
cases tested. These results suggest that both the ser‑odiagnosis and bacterial culture of specimens from theskin lesions can be valuable for diaguosis of DGI.

STUDY ON THE ISOLATION FREQUENCY OF MECHICILLIN‑RESISTANT
STAPHYLOCOCCUS AUREUS IN HOSPITALS IN GUANGZHOU, CHlNA
ZHANG KOU XlNG*, ZHANG TIAN TUOl, TANG YlNG CHUNl,
TAKASHI SHlNZAT02, NoBUCHIKA KUSAN02 AND ATSUSHI SAIT02
Department of Internal Medicine, the 3rd Affiliated Hospital,

Sun Yat‑Sen University of Medical Sciences, China* andIst Department of Internal Medicine, University of the Ryukyus2

Numerous reports of methicillin‑resistant Sta‑phylococcus aureus (MRSA) have appeared in Europe,
U. S. A, and Japan. In China, study on MRSA was begun
late and only a few reports about MRSA were published.
The isolation frequency of MRSA in Guangzhou, theircoagulase type, hemolytic activity and beta‑lactamase
production and their susceptibility to antibiotics werestudied.

168 clinical isolation of S. aureus collected fromfour hospitals in Guangzhou City, during the period fromJanuary 1991 to August 1992, were tested by the screen‑

ing culture methods for MRSA and MIC of methicillin
which showed more than 16 pg/ml.
Of all S. aureus strains, 23 (13.7%) were identified

as MRSA; 8 strains were isolated from sputum, 7 frompus, I from blood and 7 from unknown. 82.7% of MRSA

strains produced beta‑1actamase, and their colonies
showed weak or moderate beta‑hemolysis on the blood
agar. 14 (60.9%) of them were coagulase type IV. As
regards the sensitivity of the MRSA against antibacter‑ial agents, a high antibacterial activity was observedwith vancomycin and refampicin, and low antibacterial

activity with ceftizoxime, cefmetazole and amikacin.
Five strains (coagulase type VID were relatively resis‑
tant to arbekacin (MIC: 8 pg/ml) , which has not beenon the market in China.
This results showed that the incidence of MRSA in
Guangzhou was less than that in other countries. But as
the clinical use of third generation cephems has been
increasing, it is likely to be isolated more in the nearf uture .

55

3 CAUSATIVE ORGANISMS AND CLINICAL BACKGROUND OF
ACUTE RESPIRATORY INFECTIONS IN MAE SOT AREA, THAILAND
HIRONORI MASAK11, ATSUSHI TAKAHASH11, MISAO TAOl, HIDEHIKO HIROSEl
KIWAO WATANABEl, NAOTO RIKITOMll, TSUYOSHI NAGATAKE1,
KEIZO MATSUMOTO1, T. KASOMSON2, R. RUENGVERAYUDH2, C. UTHAISILP2
S. JIAMTAVEEVIBOON2, S. SMARUROTESKULCHA12, W. SWADDIWUDPONG2
T. SIRISANTHANA3 AND P. THARAVICHITKUL4
Department of Internal Medicine, Institute of Tropical Medicine,

Nagasaki University*, Mae Sot General Hospital', Department ofInternal Medicine3 and Department of Microbiology', Faculty of

Medicine, Chaing Mai University. Thailand

The aim of our presenting study is to identify thecausative organisms and clinical background of acuterespiratory infections and to provide the principle ofchemotherapeutic desigu in Mae Sot, Thailand as one of
the tropical ., countries. The investigations of adultoutpatients were performed at Mae Sot General Hospi‑

azolin and cefotiam) and also against tetracycline. In
addition, amoxicillin combined with clavulanic acid (p‑lactamase inhibitor) showed excellent antimicrobialactivity against B. catarrhalis. These data strongly
suggested that resistance of B. catarrhalis might be due

tal in Thailand for about one month each year from 1989

to the production of p‑lactamase.
From these results of sensitivity, penicillins wereto 1992. In each study, Gram‑stain of the sputum,

recommended as the drug of first choice for H.

quantitative culture of the sputum, and nasopharyngeal
culture were done for detecting causative organisms.

tion, penicillins were mainly used. On the other hand the

Minimum inhibitory concentrations (MICs) of eachuse of tetracycline decreased. However for successful

pathogen to frequently used antimicrobial agents were
determined.

chemotherapy it shoud be emphasized that most of p‑

The cultured sputum revealed major causative
organisms of acute respiratory infections mainly inacute nasopharyngitis, acute bronchitis and pneumonia
were Haemophilus influenzae. Streptococcus pneumoniae
and Branhamella catarrhalis. This results were the sameas.,those in Nagasaki, Japan. The analysis of antimi‑
crobial sensitivity to major pathogens revealed that S.

pneumoniae vyas resistant to tetracycline, gentamicin,
and norfloxacin. B. caiarrhalis showed h･igh resistanceagainst penicillins, Ist and 2nd generation cephems

influenzae and S. pneumoniae. After this recommenda‑

lactams are not active against B. catarrhalis. In addi‑tion, tetracycline is not expected for S. pneumoniae andB. catarrhalis infections. On the other hand, recently
developed new quinolones are effective to the infections
caused by both H. influenzae and B. catarrhalis.
This time, the pharyngeal fioras, related to path‑ogenesis of ARI, was compared with those in Japan. In
children H. influenzae. S. pneumoniae and B. catarrhalis

were isolated from pharyngeal fiora. In adult path‑ogenic organisms . were inf,requently detected. The
above results were almost same as found in Japan.

(penicillin G, penicillin V, amoxicillin, piperacillin, cef‑

OF BORDERLlNE TUBERCULOID LEPROSY WELL
4A CASE RESPONDED
TO THE CHEMOTHERAPY
ATSUSHI HOSOKAWAl, SHIGEO NoNAKAl, HIROKUNl KlNJ02 ANDMISAO IZU3
Department of Dermatology, University of the Ryukyus*,

National Leprosarium Okinawa Airaku‑en' and Naha City3

Leprosy( H ansen'sdisease; Hanseniasis) is achronic bacterial

inf ectious

diseasecaused by

56

Mycobacterium leprae. At first, the organism attacks theperipheral nerves, and then attacks the skin and otherspectively. And on the abdomen thum's head sizedorgans.

the all eruptions except the cheek. Hypertrophy of

In Japan the number of new leprosy patients has
been rapidly decreased in nember. In 1991, only 14

peripheral nerves is not observed. Hair loss is not seen.

patients reported in Japan (in Okinawa 6). But in the
new feature, chances should increase for the foreign

ological findings of eruption of the abdomen: Subepider‑mal clear zone is observed. Epitheriod cell granulomas
are scattered in the dermis. Laboratory data: Mitsuda

leprosy patients to enter into Japan.
In this report, a case of borderline tuberculoid lep‑rosy (BT) is reported. The patient was a 74‑year‑old
Japanese man. There is no patient of leprosy in his
family. Present history: About two months ago, anularanular erythema is found. Sensory loss is observed at

The thermogram shows normal pattern. Histopath‑

reaction shows positive (7x7 mm). Value of PGL
antibody shows negative (SERODIA‑Lepra, below16x); NKcell activity 76% (18‑40); Subset oflynphocyte in the peripheral blood shows lea 3a/2a 1.49

erythema appeared on the abdomen, and a month ago(1.59‑1.94). Persentage of B cell shows 2% (4‑13);

itching sensation appeared on the upper arms. Clinicalfindings: On the face a grain sized reddish papule andNasal and skin smear shows negative; Fite s.tain also
shows negative. Langhans giant cells are< ditected.

pea sized erythema are found. On the left upper arm,
thumb's head sized anular erythema and common eryth‑ema are found. On the left elbow, palm sized anularerythema with central healing is found. On the left
breast and right back, pea sized reddish nodulesre‑

Dense lymphocytes's infiltration around peripheral
nerves are found. Medication and process: ‑After twomonths with the medication of DDS 50 mg per day, theeruptions disappeared and the sensory loss was recover‑ed in about four months.

5 A SIMPLIFIED PROCEDURE TO INCREASE THE SPECIFICITY OF

IMMUNOFLUORESCENCE ASSAY FOR LYME DISEASENOBUYA FUJITA, HISAO ESAKI AND YUKIO YOSHIDA
Kyoto Prefectural Institute of Hygiene and Environmental Sciences

Serodiagnosis of Lyme disease is performed mainly
by use of the indirect immunofluorescence assay (IFA)

ples were diluted serially with equal volumes of absor‑

and the enzyme‑linked immunosorbent assay. Thesebent and diluted samples were then added to the test
plates for analyses in IFA. Although false‑positive

serological tests can yield false‑positive serology due toresults occured in high rate in sera from healthy persons

cross‑reactions with other spirochetes. These probrem
complicate the diagnosis of Lyme disease. The tests,
however, has not yet been standardized.

with no clinical history of Lyme disease, the use ofabsorbent effectively reduced non‑specific binding to

A commercially prepared absorbent for syphilis

significantly reducing titer of anti‑Borrelia burgdorferi

Lyme antigens to undetectable levels without

FTA‑ABS test from culture fluid of Treponema

antibodies.

phagedenis biotype Reiter made by Japan Liophilization

We present here evidence that the use of a commer‑
cially prepared absorbent can enhance test specificity.
This procedure may be helpful in the diaguosis of Lyme
disease in the laboratory.

Laboratory, Tokyo, was used in attempts to reducecross‑reactivities of serum. This reagent was chosen
for evaluation because it is commercially available andis widely used in diaguostic laboratories. Serum sam‑57

6 STUDY OF LEPTOSPIRA ANTIBODY AMONG DOGS IN OKlNAWA, JAPANYOSHIKATSU YONAHARA , KATSUMASA TOKUMURA*, EIZO KlNJ02 AND
YOSHIO SHlNGAK13
Okinawa Prefectural Institute of Public Health , Okinawa

Prefectural Animal Management Center' and Okinawa Prefectural
Meat Hygiene Inspection Center'

Rodents are important animal reservoirs for le‑ptospirosis, and recent studies have suggested that dogs

may be one of the important sources of this disease.
Some cases of human leptospirosis were reported in
Okinawa. But there were few reports about investiga‑
tion of animal reservoirs of Leptospira.

From May, 1991 to March, 1992, 750 serurn samples
from stray dogs, from 7 health centers in Okinawa, were

examined for antibody against Leptospira by micro‑
scopic agglutination test (MAT). It was done with 12
serovars of Leptospira antigens. A titer of Leptospiraantibody, >< 80 or more, was considerd positive.

One‑hundred out of 750 serum samples (13.3%)

serovar was canicola, followed by serovar pyrogenes
and javanica. But there were no positive antibody

against serovar hebdomadis, bataviae, pomona,
grippotyphosa and rachmati. Dogs in the central andsouthern areas of Okinawa mainland showed a highpositive rate of Leptospira antibody. Miyako andYaeyama areas were low. The male dog showed a highpositive rate in comparison with the female.
These results suggested that; dogs were importantanimal reservoirs of leptospira. But serovar of canine
leptospirosis is different from hurnan leptospirosis.
Clearly, further studies are required with other animalreservoirs in order to prevent human leptospirosis.

showed positive reaction by MAT. The most prevalent

7 EPIDEMIOLOGY OF JAPANESE ENCEPHALITIS IN JAPAN WITH
EMPHASIS ON THE EFFECT OF VACClNATIONISAO EBISAWA
Keihin Railway Clinic

The Japanese encephalitis (J.E) cases and deaths

decreased in revers relation to the increasing production

declined markedly in Japan in recent years, although it
is still highly endemic in the Western Pacific rice grow‑of insecticides for use in the rice field, reducing the
population of vector mosquito Culex tritaeniorhyncus.
There was a marked reduction in the ratio of fatal
cases below 15 years old among total fatal cases: 56.8%

ing regions.

I reviewed current status of JE in Japan and tried to

see why the JE patients decreased and to see theeffectiveness of JE vaccination as it was confirmed
outside Japan, in Taiwan and Thailand using a placebo

in 1950s to below 2% in 1980s. The declining trend
started from 1958, 3 years after JE vaccination forchildren below 12 years was started in 1955. The same

National health statistics, production of insecticides

trend for those more than 15 years old started about 6
years later. But the declining trend was greater in thefor use in rice fields and the amount of JE vaccine soldyounger than in the older, unvaccinated group. The

on the market since 1955 were reviewed and analyzed.
Over a period of 44 years from 1947 both patients andregression coefficient in the two groups were ‑ 0.1380
and ‑ 0.1051, which were significantly different ( P <deaths declined from the peak of 5,196 and 2,430 in 1950

fatal cases in 8 geographical districts is confirmed but0.05). The ratio of fatal cases among total deaths
became constantly less in the vaccinated than in theunvaccinated group since 1958. These results may beclear indications of the effectiveness of the vaccine.

south‑western Kyushu and Kinki districts still counted
36 and 22 deaths in 1980s. The number of JE patients

Increasing use of mosquito nets in the window, decreas‑
ing number of farming animals and dislocation of pig‑group.

to 55 and 10 in 1990, although JE virus circulation innature is confirmed each year. A marked decrease of

58

pens f rom farm houses contributed to cut human mos‑quito contact.

8 HEALTH CONSULTATION OF JAPANESE STAYING OVERSEA'SDEVELOPlNG COUNTRIESKOICHlRO FUJITA1. YASUO YANAGISAWA1. SEIICHI YAMADA1,SETSUKO TSUKIDATEl, HIROSHI OHARA2, MITSU NARAOKA3 AND

MASAKAZU TASHIR03
Department of Medical Zoology, Faculty of Medicine, Tokyo Medical
and Dental University*, Department of Medical Zoology, Saitama

Medical College2 and T‑PEC Co. LTD.'

The tropical zone includes wide areas, big popula‑tion and huge natural resources. In this sense, thetropical zone is a greatly promising object of the culture

and civilization of the future world. Now many
Japaneses are inclined to go abroad to tropical coun‑tries, but there are many problems relating to humanwelfare and health in tropical countries. Japanese intropical countries are often suffered from the diseases
which Japanese medicical doctors can not understand,and many problems urgently needed to be solved exist inthese Japanese staying oversea's developing countries inthis year.

9 FEATURES OF INFECTIOUS DISEASES IN BOAT PEOPLE INOMURA IMMIGRATION CENTER

SHINOBU KOBAYASH11, FUMINARI SONODAl, MORITOSHI AKIYAMA1,TSUYOSHI NAGATAKEl, MARIKO MATSUNAGA2, HATSUE KUD02,
TATSUO SHlNAGAWA2, TOSHlNORI UTSUNOMIYA2 AND KEIZO MATSUMOTO1
Department of Internal Medicine, Institute of Tropical Medicine,

Nagasaki University

and Omura lrnrnigration Center'

We investigated the incidence of parasitic infesta‑
tion and hepatitis B virus (HBV) infection in people,

tion was 58% among 288 Vietnamese. Identified para‑sites mainly consist of Trichuris tricura and hook worm.

who were received from May, 1989 to July, 1990 in

Positive rate of HBS antigen was 18.5% among 286

Omura Immigration Center. 1,386 people have parasitic
infestation (66%) among 2,114 Chinese. Identified para‑sites mainly consist of Trichuris trichura and Ascaris

Vietnamese.

lumbricoides. There was no siguificant difference in theincidence of parasitic infestation between men andwomen. Prevalence of HBV infection in 1,517 Chinese
people was 21.8%.
On the other hand, the incidence of parasitic infesta‑

Recent reports show that the incidence of parasitic

infestation and HBV infection is 0.12% and 1‑1.5% inJapanese, respectively. Thus, our data of parasitic
infestation and HBV infection in Omura Immigration
Center support the high incidence of both infections, andimply the current condition of hygiene in China andVietnam.

59

10RESISTANCE

OF

MICE

lNTERNAL

IMMUNIZEDW皿HSTRUCTURAl。PROTEINSKuMATO
Departmentof

INDIVIDUAL

TO

I、ETHALRABIES

VIRUS

INFEC皿ON

MIFuNE

Microbiology，Oita

MedicalMice were vaccinated with recombinant vacciniavims（rVac）expressing the glycoprotein（G），nucleo−rVac−M−vaccinated

mice

not

protected．Anti−G

antibodies

weredetected

protein（N），phosphoprotein（NS）and

the

sera

had

vaccinated（M）ofrabies

virus

and

infectionMicevaccinatedwithstrongantibody

responses

toallsurvived

essentiallyMicevaccinated

only

a

slightstreetrabiesrVac−G

protection（59％）wasNwas

examined．

rVac−N

developed

lenge

resulted

mice

given

corresponding

ProteinsrVac−NStransfer

which

and

of

been

survivedanti−Ninasignificant

F（ab7）2were

was

not

rVac−Mdeveloped

andthe50％effective

response，however，asignificant

clonalantibody

was

that

anti−GvirusorobservedintherVac−NS−vac一ofcomplete

with

were
in

rVac−

infection．Pas−

IgG

prior

to

chal・

protection，whereas

notantibodies

challenge

notchallenge

monoclolal

protectionrVac−NS

antibody

mice

infection、

mice

with

or

or

of

sive

to

virus

the

proteinmice，whereas

peripheral

resistancelethal

and

with

their

matrixcinated

University

allprotected．However，the

even

with

dose

higherofapproximately10times
neutralizing

amountanti−Nofmono・

higherthanantibody．

11 DETECTION OF DENGUE VIRUS IN DENGUE HEMORRHAGIC FEVER（DHF）
AND DENGUE FEVER（DF）BY USING POLYMERASE CHAIN REACTlON（PCR）
KouICHIMoRITA1，MARIKO TANAKA1，AKIRA IGARASHI1，P．NIMNAKORN2，
S．KANuNGKID2，S．VoNGcHEREE3，K．RuEcHusATsAwAT3，
S．RoJANAsuPHoT3，P．WARAcHIT3AND K．KANAI3
Department

NagasakiDengue／dengue
otypesofdenguehemorrhagic

virus

is

countries．

Dengueoccurschildrenamong

ever，theearlymechanismofdiagnosis

Recently，wehave

whitch

can

be

using

at

denguethevirus

specimens

hemorrhagic
detected

from

fever

specimens

fever（DHF）often

report

the

DHF

is

not

is

not

yet

developed．

and

a

in

a

of

single

yet

PCR

and

methoddengue

virus

tube

reaction

nuids（J．Clin．Microbiol．

imported

appliedthemethodsto

dengue

fever

viral

and

denguepatients

andgenome

was

all

of

specimens（manuscript

in

this

systemacute

carried

We
tive

into

dengueepidemicarea，

Hospitalofe伍cacyatinadmittedofthecontacted81acute

rate

admission

Thailand，and

patients、Insystemindengue

cases

this

epidemic

was45％．The

examined
paper，we

area．

and

PCR

positive

posi・

rates

of

day2，3，4，5，6were88％，50％，31％，11％andO％

respectively．Especially，the

group

the

hospital

no

on

day

2

and

had

who

admittedanti−dengue

antibody，

shown100％PCR

positives，indicatinghighe伍cacyat

infection、On

other

of

PCR

hand，ELISA

very

early

positive

phase

rate

at

of

diagnostic

admission

thewas48％．

When we combine both ELISA and PCR results，diag・
nostic efncacy of dengue becomes85％at any phase of
infection，No

preparation）．

We

Health，Thailand3

feta1．How−

known

rapid

serotyping

time

infectedofPhanomserum

the1991．，Vol29．，p．2107−2110）．We
clinicalNakhomtropicalinsometimes

same

Medicine，

Hospital2andby4ser−healthisestablishedTropicalcaused

fever

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Institute

andidenti丘cation

done

Virology，InstituteNational

signi丘canthemorrhagic

laboratory

by

a

of

University1，Nakhomphanom

betweensignificant

differences

primary

secondly

and

of

PCR

infection

positive

was

rate

observed．

60

12 DISTRIBUTION OF MALARIAL PARASITE AMONG FEBRILE CASES
IN SOUTHEASTERN PART OF BANGLADESH
KAMRUDDIN AHMED1, AMlNUR RAHMAN2, TSUYOSHI NAGATAKEl,
TCHMlNA HOSSAlN3, MOHAMMAD AKRAM HOSSAlN2 AND KEIZO MATSUMOTO1
Department of Internal Medicine, Institute of Tropical Medicine,

Nagasaki University*, Dhaka Medical College, Dhaka, Bangladesh'and Ministry of Health and Family Welfare,

Government of Bangladesh'

The distribution of dlfferent Plasmodium species
causing malaria among the fever cases attending two
selected rural health complexes in the south‑eastern

The prevalence of MP positive cases were more among
males (50.86%) than female (38.46%). In the tribal

part of Bangladesh was investigated in this study. The( p < 0.001 ) Iow than in the nontribal population

population the parasite rare (16.13%) was significantly

parasite rate was 45.88% among 194 fever cases of(51.53%). In the tribal population 80% of the infection

which 58.43% were due to P. falciparum, 31.46% due to
P. vivax and 10.11% due to mixed (both P. falciparumand P. vivax) infection. The highest rate (61.53%) ofmalarial parasite (MP) was found in 1‑4 years of age
group. In almost all age groups the distribution of P.
falciparum was higher than P. vivax or mixed infection.

was due to P. falciparum and 20% due to P. vivex.
However in the nontribal population 57.14% were P.
falciparum, 32.14% were of P. vivex and l0.72% were of
mixed infection. In lower socioeconomic group the MP
positivity rate was higher and the falciparum was the
predominant parasite.

13 OCCURENCE OF MALARIA IN PASSENGER OF A BRITISH SHIP
KENJI KAWAKAM11, YOSHIAKI UTSUNOMIYA1, HIROAKI MITSUSHIMA2,HIRONORI MASAKll, KAMURUDDIN AHMEDl, TSUYOSHI NAGATAKEl,
KEIZO MATSUMOTO1, SHUSUKE NAKAZAWA2, TETSUO YANAG12,SHIGEYUKI KAN03 AND MAMORU SUZUK13
Department of Internal Medicine* and Department of Protozoology',
Institute of Tropical Medicine, Nagasaki University andDepartment of Parasitology, Gunma University School of Medicine3

Malaria is one of the most common infectious
disease in the world, there are risk of malarial infectionin the epidemic area. The ship doctor requested us tohelp to diaguose malaria. The ship went to Solomon
Island and Papua New Guinea for two months about six

to P. vivex and Plasmodium falciparum (P. falciparum) .
Two serum samples had high titer of antibody against P.
vivax ( x 1,024 and x 64) and three serum samples hadhigh titer of antibody against P. falciparum ( > x 16).

From this result, we could diagnose P. vivax in twomonths ago. Patients had fever or history of fever andpatients, P. falciparum in three patients and suspected P.

some of them had other symptoms, such as headache,falciparum ( x 4) in 8 patients. 48 patients have low titernausea, diarrhoea, myalgia etc. The Ship doctor( < x 4) for malarial parasite, we think they may havediagnosed malaria in 59 patients and treated them with
antimalarial drugs, fansidarTM, chloroquin, and other

antimalarial drugs. We examined blood smears of 63
patients by Giemsa stain and we had two positive
smears of Plasmodium vivax (P. vivax). The antibody

no malaria. Though the malaria epidemic is absent inJapan, Japanese health personel should be careful about
the occurance of malaria in such circumstances, serum

antibody testing is an useful diaguostic method for
malaria.

61

14 MALARIA AND GLUCOSE‑6‑PHOSPHATE DEHYDROGENASE DEFICIENCYIN SOLOMON ISLANDAKIRA ISHI11, SATSUKI KAWABATA2, MITSUYOSHI KUMADAl, HIROKO ASAHll,
KEIKO KATOl, KIYOKO KAME13, SAEFAFIA4 AND J. LEAFASIA'
Department of Parasitology, National Institute of Health, Tokyo*,

Department Medical Zoology, Teikyo University School of Medicine',
Blood Laboratory, Central Hospital of JOCV Ofiice' andMedical Training and Research Institute, Solomon Island'

In Solomon Islands, south west pacific, malaria ishighly endemic. After malaria eradication programme
in 1970s, malaria control programme has been carried(16194) in students and 24.1% (14/58) in blood donors.

Malaita showed 10.7% (11/103) and 4.0% (11/275),

out until now. Still average annual malaria incidence isrespectively. Students from Central province showed
18.8% (12164) deficiency rate and blood donors fromas high as 2‑300/1,000. Various methods of malaria

Guadalcanal showed 14.6% (12/82) and from New

control trials have been conducted including DDT spray,

Georgia showed 11.3% (8/71) deficiency rates.

mass drug administration and use of insecticide im‑pregnated mosquitoe net and so on.

These rates of deficiency were remarkably high.
Fortunately students did not show anaemia with highHb level of 14.32 (1.85 g/dl) in average. However, in

For the treatment of malaria, they have problem ofgrade I chloroquine resistance. In the use of prima‑

the Central Hospital some patients admitted withquine, glucose‑6‑phosphate dehydrogenase (G6PD)

hemolysis. However, the rates did not correspond the

deficiency is a serious problem in Solomon Islands. If
the genetic deficiency is severe, spontaneous hemolysis

present day distribution of malaria endemicity although
in some islands such as Malaita, Guadalcanal and Cen‑
tral province are the major malarious areas. History of
habitation in e ch islands by different ethnic groups andmay occur and also on drug use such as primaquine.
This prevents the radical cure of Piasmodium vivax
infection and the use of it in chemotherapeutic malariainterrelation are considered to be the source of thecontrol activities.

present day deficiency rates in those islands of anthropo‑

We examined the prevalence of G6PD deficiency in
Solomon Islands by the use of Fujii's method which issimple and suitable for field study. Among 326 middle
and high school students gathered from various islands,
47 (14.4%) showed G6PD deficiency in average. Among
632 blood donors in the Central Hospital of Honiara, 53(8.4% ) was found G6PD deficient by cyanmethohaemog‑

logical interests.

lobin method including intermediate type. Overall

must be careful to avoid hemolytic crisis in G6PD

agreement between the two methods tvas 94%.

deficient subjects. Although the rate of hemolysis wasreported low up to 18% and practically caused no trou‑
ble in Thai subjects, we have to examine the individualsof G6PD deficiency in Solomon Islands. Fujii's method

Melanesians was the highest group showed 8.6% (50/582) deficiency followed by Polynesians 6.0% ( 3 / 50).

Twenty six Micronesians did no not show deficiency.
Rates of deficiency varied greatly in each islands rang‑
ing from O to 50%. In more than 50 islanders examined,
Santa Ysabel islanders showed deficiency rate of 17.0%

Moreover, these high rates of G6PD deficiency pose
problems in malaria control in Solomon Islands. Single
45 mg dose primaquine is used in the chemotherapeutic
control of malaria. To pursue the effect of gametocyte
killing of primaquine in the transmission of malaria
which is proven to be successful in North Sumatra, weusing agar gel plate is simple and very useful in the fieldof malarious areas.

62

15 DNA DIAGNOSIS OF MALARIA USING PCR TECHNIQUESKAORI KUNISADAl, MEIJI ARA12, HIROMI NAKAN03, SATOSHI NAKAGAM13,
AKIO YAMANE3, AKIRA ISHI14, MANABU SASA5 AND YUSUKE WATAYAl
Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical
Sciences, Okayama University*, Department of Parasitology,
Okayama University School of Medicine2. Central ResearchLaboratries, Wakunaga Pharmaceutical Co. Ltd.3
Department of Parasitology, National Institute of Health, Tokyo'
and Toyama University of International Studies5

We have developed three DNA diagnosis systems
for detection of malaria parasites in human blood using

DNP antibody. Both P. falciparum and P. vivax parar‑
ites were detected without distinction by the ED‑PCR.
The microplate hybridization is a diagnosis system

the polymerase chain reaction (PCR) techniques. Our
systems are simple and require neither DNA extraction
nor radioisotopes. The double PCR is highly sensilive

which can detect P. falciparum and P. vivax distinctive‑

and specific detection system of Plasmodium falciparum

vivax‑specific probe to detect the PCR products. In thisparasites using two‑step PCR. The target DNA

method, the part of 18 S rRNA gene was also used as thesequence used in the double PCR was that encoded byparasites in 10 pl of blood gave a positive band of 226
base pairs (bp) by agarose gel electrophoresis of the
PCR products. In the ED‑PCR, enzymatic detection of
PCR products, we have chosen a part of 18 S ribosomal
RNA gene of P. falciparum and P. vivax parasites as thetarget DNA for the PCR amplification.
We studied these three DNA diaguosis systems in
the Guadalcanal of the Solomon Islands, where is ahighly endemic area of malaria. 101 blood samples from98 people were examined by the DNA diagnosis systems
and microscopy. The results of our systems well accord‑
ed with that of microscopic examination. Our systems
were also proved to be useful for a judgrnent of thetarget DNA. The PCR products labeled with dinitro

effects of treatments.

the dihydrofolate reductase‑thymidylate synthase(DHFR‑TS) gene of P. faliciparum. As little as lO

ly, using the P. falciparum‑specific probe and the P.

phenyl (DNP) were detected using enzyme‑labeled anti‑

16

COMPLEX II (SUCClNATE‑UBIQUINONE OXIDOREDUCTASE=FUMARATE REDUCTASE) IN THE RESPIRATORY CHAIN OF
PLASMODIUM MITOCHONDRIAKIYOSHI KITAl, AKATSUKI KOKAZE1, SHlNZAZURO TAKAMIYA2,
TAKASHI AOK12, KAZUYUKI TANABE3 AND SOMEI KOJIMAl
Department of Parasitology, The Institute of Medical Science,

The Tokyo University*, Department of Parasitology, Juntendo
University School of Medicine2 and Department of Biology,
Osaka Institute of Technology3

The mitochondria of mammalian Plasmodium haverence of the NADH‑fumarate oxidoreductase systembeen variously described as cristate or acristate, or as

which is an anaerobic respiratory chain found in many
parasitic animals such as Ascaris suum has been shown.

being absent altogether. Over the past decade, moreevidence has accumulated to suggest an active role ofthe intraerythrocytic Plasmodium mitochondria and thiswa confirmed by ‑the establishment of the protocol for
isolating the mitochondria from Plasmodium. From thebiochemical analysis of the purified mitochondria, occur‑

In this system, complex 11 functions as terminal oxidaseand catalyzes the reduction of fumarate to succinate(fumarate reductase: FRD) . This enzyme complex
functions in reverse direction as succinate‑ubiquinone
oxidoreductase (SDH) in the aerobic respiratory chain

63

of mammalian mitochondria.
Mitochondrial complex 11 is generally composed offour polypeptides and appears to be a highly conserved
enzyme complex. The largest fiavoprotein subunit (Fp)seem to be essential for the interaction between thecomplex and quinone species. When Plasmodium mito‑
chondria was analyzed by Western blotting using anti‑
Ascaris Fp antibody, cross‑reacting band with same sizewith ･a molecular weight of about 70 kD contains

as Ascaris Fp was observed. This result indicates acovalently bound fiavin, and the second largest subunit

presence of fumarate reductase in the Plasmodium(Ip) with a molecular weight of about 30 kD contains

mitochondria and antigenic similarity in the enzyme

iron‑sulfur clusters. The Fp and lp subunits are hydro‑
philic and form a catalytic portion of the enzyme com‑plex that transfers reducing equivalents from succinate
to water‑soluble dyes such as 2, 6‑dichlorophenol indo‑

complexes between the two parasites. So, we havephenol (SDH) or from reduced methyl viologen to
fumarate (FRD). Two small hydrophobic membrane‑

mixed primers for polymerase chain reaction (PCR)
and subsequent sequence analysis were applied toanchoring polypeptides with molecular weights of about
15 kD and 13 kD (cytochrome b subunit; cybL and cybS)

detemine the partial CDNA sequence of Fp and lp

started to study the fumarate reductase of Plasmodium
to know the unique properties of the respiratory chain
and its energy metabolism. Homology probing by using

subunits in the fumarate reductase from Phomodium .

17 ISOLATION AND PURIFICATION OF DIHYDROFOLATE REDUCTASE OF
PLASMODIUM FALCIPURUM USING SYNTHETIC DHFR GENE
GEN‑ICHIRO SANO AND TOSHIHIRO HORII
Department of Protozoology and Parasitology, Research Institutefor Microbial Diseases, Osaka University

For the rapid invention of anti‑malarials, we havedeveloped the system for preparing a large amount of
the target enzyme, DHFR (dihydrofolate reductase) of

Piasmodium falciparum. Our system involves the syn‑thetic P. falciparum DHFR gene which is designed forshowed DHFR' activity. The fraction was followed by
the further purification processes including Hydroxy‑
lapatite and Sephacryl S‑300 column chromatographies.
We obtained 10 mg of DHFR with a purity of more than98% .

the efficient expression in E. coli. When we induced the

The Km values of our purified DHFR and NADPH

artificial DHFR gene into E. coli, the product with amolecular weight of 27 kD was accumulated in the cell.
However almost all of the products were precipitated in
the form of inclusion body. Therefore, we solubilized
the precipitate with a buffer containing guanidine ‑hydrochloride and renatured by diluting with a excess
amount of phosphate buffer. Thus renatured fraction

were respecticaly 15.0 pM and 19.6 pM. These values
for both substrates are similar to those of partiallypurified DHFR from P. falciparum reported by Kan andSiddiqui (J. Protozool., 26, 1979, pp. 660‑664), therefore

it is suggested that our purified DHFR has the samekinetic properties to the native DHFR.

18 AN ANTIMALARIAL ACTIVITY OF DILAZEP AND DIPYRIDAMOLEYOSHIHIRO ITO1, 2 AND MASAMICHI AIKAWAl
Case Western Reserve Universityl and Institute of General Beautyand Medical Science2

An antimalarial activity of dilazep and dipyr‑
idamole was investigated by using a continuous culture

system of Plasmodium falciparum. When 2 pM of dil‑azep or 3 pM of dipyridamole was added to the culture,

the parasitemia was reduced siguificantly on day 4. The
inhibitory effect appeared parallel to the concentrationof these drugs. The antimalarial activity was also
observed when these drugs were added to the culture64

containing uninfected erythrocytes 24 hr before Plas‑
modium falciparum infection. These results indicatethat dilazep and dipyridamole might act on the eryth‑rocyte membrane, thereby inhibiting erythrocyte inva‑
sion by Plasmodium falciparum.

19 OVALE MALARIA‑LIKE MORPHOLOGICAL CHANGES OF THE PARASITIZEDRED CELLS IN TERTIAN MALARIAHIROYUKI AMANO , TOSHIMASA NISHIYAMA2 AND TSUNEJI ARAK12
Department of Overseas Medical Servrces Tenn Hospital and Department of Parasitology, Nara Medical Univesity2

Differential diagnosis of malaria is based on themorphological characters of parasites and parasitized
red cells in thin blood smears. Individual immune situa‑
tions and drugs used can transform malarial parasites.
Red cells can also change shapes due to not only congen‑ital and acquired factors but also techniques of bloodsmear preparation. Therefore, it is sometimes difficult
even for specialists to differentially diagnose the four

malarial species, especially between Plasmodium vivax(Pv) and P. ovale (Po) , or P. falciparum and P. malar‑iae. In this study, we examined the frequency of ovale
malaria‑like morphological changes of parasitized red
cells in thin blood films of some tertian malaria cases,
because a smear in an Indian Pv case (Pv/Po) with high

IFA titer to Pv antigen revealed many parasitized red
cells had changed morphologically. As a rule, th̲e, ,. firstthin blood , films from 2 Po, I Pv/Po and 16 Pv cases were

examined. Morphological changes was classified into
three groups, ie. 1) fimbriation only 2) elongation only

and 3) both fimbriation and elongation. These wererepresented as percent frequency. Frequencies offimbriation only, elongation only and both fimbriationand elongation were 25.6% , 11.8% and 25.1%, respective‑
ly in Po. In Pv/Po, these were 34.0%, 7.6% and 5.2%,
whereas in Pv, only 1.6%, 0.2% and 0.6%. This result
may show that Pv/Po cases are caused by a peculiar Pv
species.

20 ANTIBODIES INHIBITlNG THE ATTACHMENT OF PLASMODIUM FALCIPARUM
INFECTED ERYTHROCYTES TO TARGET CELLSSHUSUKE NAKAZAWA, TETSUO YANAGI AND HIROJI KANBARA
Department of Protozoology, Institute of Tropical Medicine,

Nagasaki University

Three kinds of immunological assays, antibody ‑mediated agglutination of erythrocytes infected with

C32 melanoma cells. A homologous pair, IRBCS of an

mature stages of Plasmodium falciparum (IRBCs) , inhi‑

isolate MS815 and homologous serum, showed a positive

MS804, but no sera inhibited the attachment of them tobition of attachment of IRBCS to C32 amlanotic

agglutination and inhibition. Both of the positive agglu‑

melanoma cells and IFA on the surface of alive IRBCS(surface IFA) , were conducted by using IRBCS of sev‑
eral P. falciparum isolates and sera from animals im‑
munized with IRBCS and from patients to confirm thattination and inhibition were not found on the other seven

these sera contained the antibodies binding to the sur‑face of alive IRBCs.
Sera from eight acute falciparum malaria patientssera.

were ̲ examined dn the assays by using IRBCS ofpatient one month before the recrudescence by using
homologous parasite isolates. Although the recrudes‑

homologous parasites which were established in in vitro
culture. All eight sera agglutinated IRBCS of an isolate

pairs. Surface IFA were negative for all the sera. It
was suggested that the titers of antibodies binding to thesurface of alive IRBCS Were low in these acute patient

On the assays serum from a recrudescent patientwas compared with the serum taken from the samecent serum showed stronger agglutination and inhibition

65

of IRBCS of both homologous isolates than the one ‑month‑before serum, it showed negative surface IFA as
well as the latter serum. A recrudescent serum might
not necessarily contain high titers of specific antibodies.

Immunoglobulin G were purified from a rabbit

serum by using Ampure PA (Amersham) to obtain
positive surface IFA. The lgGs agglutinated IRBCs,
inhibited the attachment of IRBCS to melanoma cells

Mouse sera and rabbit sera, which were taken fromand gave a positive result to the suface IFA. A quantita‑

the animals immunized with IRBCS of strain M,

tive correlation was found between agglutination andinactivated and treated with human O group eryth‑inhibition assay titers of the lgGs solution and of theoriginal rabbit serum. While the original serum and therocytes to remove antibodies binding to erythrocytes
surface, gave positive results to the agglutination andinhibition assays. While rabbit pre‑immune sera did notlgGs solution showed almost the same titers in the

agglutinate M strain IRBCs, mouse pre‑immune sera

out an lgG component showed very low titers in the two
assays. Agglutination was detected at higher dilution of
the lgGs solution than surface IFA.

agglutinated them. Surface IFA was negative for mouse
immune sera. Rabbit immune sera did=not show surface

agglutination and the inhibition assays, the serum with‑

IFA clearly.

21 NEUROPATHOLOGICAL FlNDlNGS OF BRAINS OF MALARIA TROPICAMIROKU YAMASHITA
Honor‑director of Osaka Kaisei Hospital

I want, though insuficient data, to report aboutmacroscopic findings of brains and abdominal organs of
45 Japanese soldiers, suffering from acute and serious
malaria tropica in Bataan Peninsula battle fields inlocalization put us in mind of spongy oedema by Creutz‑

feldt=Jakob's disease. I remember Pfeifer's "Die an‑Philippine, who died suddenly as soon as arrival togioarchitektonische areale Gliederung der Grosshirnrin‑de, Leipzig 1940". Small superficial pialartery arriving
to the bottom of windings valley, deeply passing throughhospital and in a few days in spite of sufficient medical

grey matter, spread many rectangular precapillarytreatments in our basic hospital in Quezon City frombranches and farther capillary branches rectangulary.
This repeated rectangular remification may be locus
minoris of haemorrhage. Secondary: rather larger haem‑
orrhage in brainstem esp. in pons.

April to July 1942. These 45 soldiers were all belonged

to a newly organized army division in Japanese homeprovince. Accordingly they had no anamnesis ofmalaria infection. And also two cases in southern China,

Microscopic findings of one of two cases in China: I

which given to me from field hospital in 1938, microscop‑

saw embolus of capillary and precapillary within malar‑

ically studied in Neuro‑Psychiatric Department of Kyu‑
shu University in Fukuoka. These two cases were welliapigment and lymphocyte included, its surrounding

and sufficiently treated.

Clinical symptoms were generally high fever inevery day, anemia, enlarged spleen, delirious and thencomatose condition, convulsion and many kinds cerebral
symptoms. At last suffered a loss by heart diseases.
Macroscopically summarized in 45 brains, I obser‑
ved the two kinds of haemorrhage. At first: precapillary

and capillary haemorrhages bandlikely arranged
between cerebral grey matter and white matter. This

area･ is chaemic necrosis, fatt r soft degeneration andmicro‑, astro‑ glial proliferation i.e. Diirck Malaria

Granuloma. In white matter of both cases were seen
venous staguations.

Abdominal organs: Enormous darkred spleens wereseen just as to burst, maximal size reached 25x 10X8

cm. Liver showed wedge‑shaped white infarct, its
maximal superficial diameter ca. 5 cm. Kidney also had
2 cm diameter of white‑infarct.

66

22 DEEP VASCULAR SCHIZOGONY IN INTRADERMAL CAPILLARIESIN FOOT PAD OF PLASMODIUM COA TNEYI INFECTED RHESUS MONKEY‑INTRAD ERMAL METHOD FOR MONOTORING CEREBRAL MALARIA‑
SHIGEYUKI KANOl, SATORU KAWA11, KENJI KASHIWABARA2,MASAMICHI AIKAWA3 AND M･AMORU SUZUK11
Department of Parasitology , and Department of Pathology2 ,Gunma University School of Medicinel and Institute of Pathology,

Case Western Reserve University School of Medicine3

Severity of falciparum malaria in cerebral malaria
patients is reported to be not necessarily related toperipheral circulatory parasitemia, but to the degree ofparasitized red blood cell (PRBO sequestration in
cerebral microvessels. The sites of deep vascularschizogony by Phomodium coatneyi (P. c. ) have been
investigated by several researchers. And, recently,
Aikawa et al, established a primate model for the studyof human cerebral malaria by demonstrating P. c.‑par‑asitized red blood cell sequestration and cytoadherenceof knobs on PRBC to endothelial cells in the cerebral

devised an intradermal method for obtaining the degreeof deep vascular schizogony using a P. c. ‑infected rhe‑

sus monkey: a spot on the foot pad of the monkey was
punctured intradermally at least 10 times using a 27 G
needle from different angles, in order to damage thetissues and free schizont‑infected erythrocytes from themicrovessels. A drop of blood was squeezed out of the
spot onto a glass slide. And blood smears taken by thismethod were contrasted with those taken simultaneous‑ly from the ear lobe. It was proved that parasitemia of
the schizont‑infected erythrocytes observed in the blood

microvessels of rhesus monkeys (Macaca mulatta).

smear made by the intradermal method from the footHowever, obtaining a brain smear for the oxaminationof sequestration from a cerebral malaria patient is
impossible. And yet, watchful and adequate manage‑
ment requires the cerebral malaria be differentiallydiagnosed from the other causes of cerebral manifesta‑

pad was always significantly higher than that obtained
from the ear lobe. And it was also worthy of our noticethat the zig‑zag pattern of the change of daily par‑asitemia of ring form‑infected and schizont‑infectederyihrocytes were just the opposite. We could say thatthe degree of deep vascular schizogony at the foot padtion, and that progression of severity be closely monitor‑

ed during the entire clinical course. Therefore, patho‑
logical evaluation of the severity of cerebral malaria is

still very difficult but necessary. So that we have

could be very well shown by the intradermal method,
and the severity of cerebral malaria could thus bemonitored successfully by the method.

23 ROLES OF y/6 T CELLS IN PROTECTIVE IMMUNITY AGAINST MALARIAMORIYA TsUJ11, PETER MONBAETERS2, RUTH S. NUSSENZWEIG1,

SUSUMU TONEGAWA2 AND FIDEL ZAVALAl
Department of Medical and Molecular Parasitology, New York
University School of Medicine* and Department of Biology,
Massachusetts Institute of Technology'

A number of studies on protection induced by immu‑

nization with malaria sporozoites have demonstrated

Plasmodium yoelii, we studied the anti‑malaria immune
response in mice deficient in a/p or y/6 T cells. These

that antibodies and T cells bearing CD4 and CD8 play animportant protective role. These T cells, which seem tomice were generated by introducing germ line mutations

eliminate malaria parasites by attacking the liver(y/( T cell deficient) .

stages, express a/p T cell receptor (TCR) .
In order to define the possible role of non‑a/p T
cell populations in immunity against the rodent malaria

in either the TCR‑a. P (a/p T cell deficient) , or 6 genes

When a/p T cell deficient mice were infected with

non‑lethal strain of P. yoelii, they developed un‑controlled ascending parasitemias. Differently, normal

67

mice were capable of controlling and clearing the bloodparasitic activity. In fact, the depletion of y/(

infection. The course of parasitemia in y/( T cell
deficient mice was similar to that observed in normal
mice. These results indicate that a/p T cells arein vivo administration of anti‑y/6 antibodies, strongly

T cells
in sporozoite‑immunized a/p T cell deficient mice, after

abolished the protective immunity. These results

Immunity against the liver stages appears to bedifferent. Immunization of a/p T cell deficient micewith irradiated sporozoites induced an immune response

strongly suggested that y/6 T cells could mediate theanti‑malaria immune response observed in these mutant
mice.
Finally, we isolated two yl( T cell clones frommalaria‑immunized a/p T cell deficient mice. Adoptive
transfer of one of these y/( clones to normal micesignificantly inhibited the development of the liverthat significantly inhibited the development of the liver

stages of the parasite.

essential to control the parasite infection of blood cells,

and strongly suggest that y/( T cells do not have amajor protective role against the blood stages of theparasite.

stages, indicating that non‑a/p T cel･Is have an anti‑

24

BASIC STUDIES ON THE MONGOLIAN GERBIL AS A SUSCEPTIBLE HOST
TO FILARIAL INFECTION (lO) UMBILICAL SCENT GLAND
M. MWANATAMBWEl, GORO ASANO1, MASUMI SHIMIZU2,3
KAZUHIRO SHICHINOHE2,3, TETSUO IEDOKOR03 AND KOICHIRO FUJITA3
Department of Pathology* and Department of Laboratory Animal
Sciences', Nippon Medical School and Department of Medical
Zoology, Facu:ity of Medicine, Tokyo Medical and Dental University'

The Mongolian gerbil is one of widely used animals
in various fields of experimental medicine, however,detail biological studies on this rodent have been lessthan those on mice or rats. The Mongolian gerbil has asome famele gerbils, it could not be found macros‑
copically on the ventral skin. The gland was packed in
the corium and orifices of the gland were placed in a line

scent gland on the umbilical skin area and it is one of theto surface of the skin. In some gland, secretion was
produced. In some female gerbils lacking the gland in

peculiar characteristics of this rodent. In this report, wemacroscopic observation, absence of the gland wasmade morphological and histological studies on thedemonstrated by a histological examination.

gland.

These findings suggested that the umbilical gland of

The gland was observed to be thickened in a spindle
or elliptical shape on the umbilical skin area. Sizes ofthe Mongolian gerbil was a sebaceous holocrine gland
which produced a scent for territorial behavior andthe gland were larger in males than in females and in

related to difficulty of matings.

BASIC STUDIES ON THE MONGOLIAN GERBIL AS A SUSCEPTIBLE HOST
TO FILARIAL INFECTION (11) SKlN SENSITIVITIES TO CHEMICAL MEDIATORS
25

MASUMI SHIMIZU ' KAZUHIRO SHICHlNOHE*'2 , TETSUO IEDOKOR0=
SETSUKO TSUKIDATE2 AND KOICHIRO FUJITA'
Department of Laboratory Animal Sciences, Nippon Medical
School and Department of Medical Zoology, Faculty of Medicine,Tokyo Medical and Dental University'

Our previous reports showed the Mongolian gerbil(Meriones unguiculatus) had basophilic granulocytes inperipheral blood and mast cells in connective tissues.
These characteristics are almost same as those of the

68

guinea pig among small rodents. In this experiment, we
carried out comparative studies on skin sensitivities tosome ch mical mediators, among gerbils, rats and guinea

mediators which induced the same size of blue spots inthree rodents were compared.
The skins of Mongolian gerbils appeared to have apigs.

high response only to histamine with almost same

Skin sensitivities to chemical mediators such asacetylcholine (Ach) , histamine, serotonin (5‑HT) andleukotriene C4 (LTC4) were compared among male andfemale gerbils (JMS strain) , male rats (Sprague‑Daw‑

degree of guinea pigs. The reaction to Ach of gerbils
was in the middle level between rats and guinea pigs.
To 5‑HT and LTC4, skin sensitivities of gerbils were
lowest among these three rodents and areas of reactions
were not enhanced with increase of doses of 5‑HT and
LTC4 in gerbils. The skins of rats remarkably respond‑
ed to 5‑HT and LTC+ but‑not to histamine.

ley strain) and male guinea pigs (Hartley strain) usinga modified method of immediate intracutaneous reaction
under conventional condition. Each mediators in ten‑fold serial dilutions in a volume of 0.1 ml was inoculated

The Mongolian gerbil was appeared to be a his‑

intracutaneously into sites on the shaved back skins ofthese rodents. Immediately after intracutaneous inocu‑

tamine sensitive rodent like the guinea pig in this experi‑

intravenously. After 30 min, areas of blue spots on thement. This characteristics including existence of baso‑phils and mast cells in gerbils may be very useful tostudy some allergic reactions during the course of filar‑

inner side of the skin were measured and the doses of

ial infections.

lations, 0.25 % Evans blue in saline was injected

26 BASIC STUDIES ON THE MONGOLIAN GERBIL AS A SUSCEPTIBLE HOST
TO FILARIAL INFECTION (11) SENSITIVITY TO EMC VIRUS M VARIANT
KAZUHIRO SHICHlNOHE '3, MASUMI SHIMIZU '3, MILANGA MWANATAMBWE2TETSUO IEDOKORO', SETSUKO TSUKIDATE3 AND KOICHIRO FUJITA3
Department of Laboratory Animal Sciences and Department of
Parasitology', Nippon Medical School and Department of Medical
Zoology, Faculty of Medicine, Tokyo Medical and Dental University'

It is well known that encephalomyocarditis (EMO
ment, we studied on sensitivities to EMC virus M vari‑

virus inoculation and after that, it returned to normal
ranges. Because blood sugar level did not increase invirus inoculated gerbils, EMC virus M variant could not

ant of the Mongolian gerbil which widely used as a

induce diabetic symptoms in the Mongolian gerbil.

susceptible host to filarial infection.

Pathological changes of virus inoculated gerbils wereseverest in pancreas among three organs. Acinar cellvirus induced diabetic symptoms in mice. In this experi‑

Conventional male and female gerbils were allocat‑
ed into 4 groups at the age of 3‑4 months. Three groups

vacuolation and fat necrosis were found even in animalsof 9 gerbils each were inoculated with EMC virus M

inoculated with the lowent viral dose. In gerbils

variant intraperitoneally (102, 5 x 102 and 103 TCID50/
0.1 ml, respectively) . Gerbils of the other group were

inoculated with the highest viral dose, islet cell hyper‑

injected with medium in the same volume of virus solu‑
tion as a control. Their food and water consumptions,body weights and blood sugar levels of gerbils were
measured during one week after virus inoculation.
Blood samples were collected from the tail vein andblood sugar levels were determined by glucose‑oxidase
method. At the time of sacrifice or death, hearts,
kidneys and pancreases were removed and tissue sec‑
tions of those organs were prepared as usual.
Average blood sugar levels of each virus inoculatedgroup of gerbils dropped momentary at the 3rd day ofplasia was observed. In hearts, atrophy of cardiomus‑
cular cells and cellular infiltration were observed inacute phase and showed signs of acute myocarditis.
Kidneys of virus inoculated gerbils were almost normalin acute phase. Degrees･of these changes of the tissues
were not different between sexes but were in proportion
to infectious doses of EMC virus.
This study suggested that the Mongolian gerbil has
sensitivity to EMC virus M variant and may be a usefulmodel to analyze relationship between viral and filarial
inf ections.

69

27 BANCROFTIAN FILARIASIS ･ IN KENYAYASUNORI FUJIMAKI G S BACHlNl2, F. MWATHE2, S.M. GAKITA2,
MAKOTO SAKAMOTOI AND YOSHIKI AOKll
Department of Parasitology, Institute of Tropical Medicine,

Nagasaki University* and Kenya Medical Research Institute'

The control project of bancroftian filariasis in
Kenya was initiated in May, 1990 under the sponsorshipto receive the night blood survey and clinical examina‑tion. A total of 436, 233 males and 203 females, wereof JICA and Kenya Medical Research Institute. The

examined for microfilariae by nucleopore filtration

main aim of the project is to understand the epide ‑miology of the disease and to find out an effective
method of control, especially to study the effect oftreatment combined with ivermectin and diethylcarbam‑

method. The microfilariae were detected in 86 or 19.7%
of subjects examined. The higher mf rate was found inazine.

from I to 2,944, with the mean of 357.5.
A total of 341 villagers, 181 males and 160 females,

According to the preliminary night blood survey,
the study areas were settled down at three villages,
Lutsangani, Dzivani and Gandini, 90 km west of Mom‑basa.

The present paper deals with the basic epidemio‑
logical survey done at one of the study areas, Lutsan‑gani, on Februry, 1991, November, 1991, January, 1992
and June, 1992.
Although the census of the study area has not been
completed, the population of Lutsangni is estimated tobe 1,lOO. The villargers over 5 years old were requested

persons over 40 years. There was no difference inprevalence by sex. The micrifilariae density varied

were examined by doctors. Twenty eight of them, 14
males and 14 females, showed one or more of acute andchronic sigus of bancroftian filariasis. For males,

epididymitis and hydrocele was most common. They
were found in 12 and 11 persons, respectively. For
females, Iymph varices was most common and it was
found in 11 individuals. Elephantiasis was found in 2
males and 2 females. Chyluria was absent.
Entomological survey is now under investigation.

28 DEVELOPMENT OF THE NEW TYPE VACClNE AGAINST THE
FILARIAL INFECTION 1. EVASIVE MECHANISM OF FILARIA FROMHOST IMMUNE SURVEILLANCE
KOICHIRO FUJITA1, SEIICHI YAMADA1, SETSUKO TSUKIDATE1,YAN YANl AND YOICHIRO HORI12
Department of Medical Zoology, Faculty of Medicine, Tokyo Medical‑
and Dental University* and Department of Parasitology,

Miyazaki Medical University'

We carried out the experiments of host immune

the evasive mechanism of the filarial worm. The new

response to the filarial infection for past 25 years. We

type vaccine is supposed to contain some elements of (1)could clearly the mechanisms of the clever evasive
mechanism of the filarial worm from host immune sur‑antibody against the 3rd stage larvae (L3) , transmission

blocking antibody, (2) activate substance of the effector

veillance. Now we intended to develope of the new typecells such as macropharge and eosinophil and (3) of thevaccine against the filarial infection after understanding

NK cells activate substances.

70

29 DEVELOPMENT OF THE NEW TYPE VACCINE AGAlNST THE
FILARIAL INFECTION 2. TRANSMISSION BLOKlNG VACClNE
SETSUKO TSUKIDA,TEl, YOZABURO OIKAWA2, TERUAKI IKEDA2 AND
KOICHIRO FUJITA1
Department of Medical Zoology, Faculty of Medicine, Tokyo Medical
and Dental University and Department of Medical Zoology,
Kanazawa Medical University'

Effector cells in filarial infection were determined tobe macrophages and eosinophils. And these effector
cells worked only to the 3rd stage larvae (L3) . We haveproduced monoclonal antibodies raised by Brugiza pa‑
hangi L3 antigen, and have obtained monoclonal anti‑

bodies recognizing a stage‑ and species‑ specific30

antigen. When this antibody was given to the B. pahangi
infected mice, the infection and recovery rates of thefilarial worm from the mice were obtained to decreasesignificantly. The antigen recognized by the monoclonal
antibody disappeared from the surface of the 3rd .,stage
larvae within I week after infection.

MEDICAL EXAMlNATIONS OF CHILDREN IN KlNGDOM OF TONGAYOSHIYUKI OKUWAKll, MIYUKI ADACH12, NOBUKO MURAYAMA2
TAEKO OHUCH13, SHIRO IlN04, TILITILI PULOKA5 AND SIAOSI AH06
Department of Microbiology*, Department of Ecology of Humanand Food･, Joshi Eiyoh University, Kanagawa Prefectural JuniorCollege of Nutrition', Ist Department of Internal Medicine,Tokyo University School of Medicine', Ministry of Healthand Vaiola Hospital', the Kigdom of Tonga

We carried out the investigation on the relationshipbetween health and the eating behavior of Tongan.
A comparative survey have carried out to elucidate

how the designated concept of "Healthy obesity"
prevailed in Tongan adult population, among 3 area,

heavier than other population.
In Urinalysis, albuminuria and glucosuria were notdetected. Hematocrite test in blood examination
showed the range of 37‑52% in males and the range of
32‑42% in females.

Kolof60u in the capital (K area), Uiha in the isolated

As to fourteen items of blood chemistry, theisland (U area) and Manukau area in Manukau City in
New Zealand.

significance of difference between K area and U area

It is reported that we surveyed inhabitant medical
examinations of Tongan children. Subjects are consistof 85 children aged 8‑17 year.

Children have been compared with the WHO stan‑
dard in respect of weight/age, weight/height, heightlage

and body mass index (BMD. Tongan children are

was assessed on the basis of Student's t‑test. In males
and females, there were a significant difference in GOT

and GPT between K area and U area, respectively.
We studied for serological evidence of hepatitis B
virus markers. As to the results of HBV markers, 16
out of 85 subjects (19%) were found to be positive for
HBSAg, and 45 out of 85 subjects (55%) had Anti‑HBs.

71

31 A CASE STUDY OF INTERNATIONAL TECHNICAL COOPERATION
IN THE FIELD OF TROPICAL INFECTIOUS DISEASESIN NORTHEAST BLAZILSEIKI TATENol'2, HARUMI ROYAMA2 AND TSUTOMU TAKEUCH12
Department of International Cooperation, National Center Hospital*

Department of Tropical Medicine and Parasitology,
Keio University School of Medicine2

For the last 6 years, we have been participating in

the international medical cooperation project on theInterdepartmental Center for Immunopathology (nowcalled LIKA‑Laboratorio de Imunopatologia Prof.

from almost zero has become one of the leading tropicaldisease research centers in Brazil, with annual publica‑tion of more than 20 including those published in inter‑national journals. In addition, more than 30 young

Keizo Asami) in the Federal University of Pernambuco,
supported by Japan International Cooperation Agency(JICA) . It followed one of the scheme of JICA called"Project Type Technical Cooperation". The Northeast

students have already completed their master's theses
through oxperiments conducted at the Center. As theseis one of the least developed regions of Brazil and also

research grants. In this way, the crucial problem of how
to sustain the activities of the research center after thean endemic area of many tropical infectious diseases.
The project started with its objective "to improve theexperimental achievements have been recognized,
researchers in this center are now able to obtainend of cooperation project is being solved.

research on tropical parasitic diseases at the Center andThrough this project, we have detected 3 main

to contribute to the better hygienic condition in the

problems: (1) The problem of "local cost" bearing, (2)Northeast Brazil" Dunng the course of project, it

The problem on the objective, evaluation and meaning

became necessary to include as the target of researchof the research development projects, (3) The problem on

not only parasitic diseases but other infectious diseases.

clinical research, in particular endoscopic and ultrasono‑continuity in r search development projects after thecompletion. Based on our experiences, we discuss thefollowing points for each problem mentioned above: (1)graphic diagnosis, mainly aiming at schistosomiasis.
During this project, the total number of 70 Japanesetial stage of the project and our basic strategy, (2)experts were s,ent to the Center, 23 trainees were

Objective and meaning of funding a research institute inreceived in Japan and the epuipments in a total amountof 550 million Japanese yens were donated. As a result
Gf such a cooperation, the research center which started

developing countires in special reference to local costbearing, (3) Trial to obtain research grants from outer

Later, the cooperation was also extended to the area of

The condition of our counterpart institution at the ini‑f oundations.

32 ROTAVIRUS EPIDEMIOLOGY IN ZAMBIAHITOSHI OSHITANIl, MWILA MpABALWANll, FRANCls KASOLOl,NOBUYUKI MATSUBAYASH12, B.J. BHAT2, MASAHIRO WATANABE3
HIROSHI SUZUKI' AND YOSHIO NUMAZAK14
Virology Laboratory* and Department of Pediatrics', University

Teaching Hospital, Zambia, Department of Pediatrics. Mie University

School of Medicine3 and Virus Research Center,
Sendai National Hospital+

An epidemiological study on Rotavirus infection

Zambia. It also caters for population of about one

was carried out at the University Teaching Hospital (U.
T.H.), Lusaka, Zambia. This hospital has bed space ofabout 1,500 and is the main national referral hospital in

million people living within and around Lusaka.
Between November 1991 and September 1992, 1,139
stool samples were collected from pediatric patients

72

admitted to the diarrhea unit of the U.T.H. Stool

16.2%, above four years less than five yeafs: IL1'%or andsamples were tested using Rotavirus antigen detection
ELISA test kits (Rotaclone;‑.Cambridge Bioscience) andabove five year less than six years: 12.0%.
Mortality rate in Rotavirus positive cases was 9.1% .

a electron microscope (negative staining) . Of the 1,139

This is higher than that reported from developed coun‑tries. During the period of November 1991 to September

samples tested 294 were positive for Rotavirus (positive
rate: 25.8% ) . During study period there was an epidemicof dysentery in Lusaka. Rotavirus positive rate wasfound to be higher in non‑dysenteric cases (non bloody

diarrhea) (212/505, 42%) than in dysenteric cases(bloody diarrhea) (441449, 9.8%). The overall Rotavir‑

us positive rate could have probably been higher, had
there been no dysentery epidemic.
Rotavirus positive rate was higher in male (28.2%)
than in female (23.5%), but this was not statisticallysignificant. Rotavirus was more common in younger age
group, especially those less than one year of age. The
positive rate decreased with advance in age as shown
below; Iess than one year: 39.9%, above one year lessthan two years: 18.0%, above two years less than three
years: 15.4%, above three years less than four years:

1992, Rotavirus was constantly detected. Between
December 1991 and January 1992, positive rate was
10wer than subsequent months. In these months morethan 25% of samples were positive for Rotavirus.
Conclusion are as follows:
1 ) Rotavirus is the most common cause of acute diar‑rhea in Zambian children.
2 ) Rotavirus is more common in younger ag group.
3 ) Mortality rate of Rotavirus infection is high,4 ) There is no seasonal variation in Rotavirus̲.infec‑

tion in Zambia.

This work was done as a part of the Infectious
Disease Project, a technical cooperation between Japan
and Zambia. It is supported by the Japan International
Cooperation Agency (JICA) .

33 PREVALENCE OF ENTERIC VIRUCES IN CHILDREN IN KARACHI, PAKISTAN
SHlN ISOMURA , MUBlNA A.2 AND AKRAM, D.S.2
Department of Medical Zoology, Nagoya University
School of Medicine* and Department of Pediatrics,
Karachi Civil Hospital'

To study the prevalence of enteric virai infections
in children in Karachi, Pakistan.
Fecal samples were collected from patients of acutewatery diarrhea aged 5 years in Civil Hospital Kara‑chi. Feces from aged matched healthy children werestudied as controls. HeLa, HEL, RD‑18S cells wereused for isolation of enteroviruses. Rotavirus andenteric adenovirus (EAd, Ad‑40, 41) were detected by
ELISA. Antibody against hepatitis A virus (HAV) was
measured by ELISA.
During Oct. 1989‑Sept. 1991, 322 diarrheal patientsand 126 healthy children were studied. Enteroviruses
were isolated from 144 (44.7%) diarrheal and 61 (48.4%)

healthy children. Isolation positives were mainly infants

and there was no seasonal cluster. Most of the isolated
viruses were non‑poliovirus and their serotype distribut‑
ed widely.

Rotavirus were detected from 26.1% of diarrheal
and 0.8% healthy children, primarilly from infants
aged

I year.

EAd positives were 0.2% in diarrheal and O% in
healthy children. Prevalence of HAV antibody was 82%
in children in 3 years and 94% in 5 years of age.
Prevalence of enteric viral infections was promi‑
nently high among children in Karachi, especially thosein 2 years of age.

73

34

ESTABLISHMENT OF STRATEGY FOR THE PREVENTION OF
POST‑TRANSFUSION HEPATITIS B IN KENYA
MITSUAKI KOGA1, MICHITAMI YANO1, P.M.‑ TUKE12 AND F.A. OKOTH2

Institute for Clinical Research, Nagasaki Chuo National Hospitall and Department of Viral Research Centre,
Kenya IVledical Research Institute2

KEMRI and JICA have been collaborating inresearch on hepatitis B for more than 5 years in Kenya.

body raised in albino guinea pigs, because of the very
high level of antibody from small and middle scales.

The production of HBsAg diagnostic reagent has been

These results showed that we could product R‑PHA

started and we could get the first reagent kit made in
Kenya at the end of 1989. We investigated the circum
stances of production of R‑PHA cells and found that R‑

cells in large quantity with domestic materials. Further‑

PHA cells can be produced in KEMRI derived from anantibody purified in Japan from an antiserum raised insupply government blood banks to screen donated blood.
Therefore the workshop held at KEMRI was financed byhorse. Although a comparable reagent to commercial

JICA and coordinated and facilitated by both KEMRI

more the study of localy and mass production was under

way and then we had enough to do to continuously

ones could be produced in KEMRI using the horse

and JICA scientist and technologist. Participating tech‑

antibody, use of horse as a host of immunization seems

nologists and technicians, were drawn from 8 govern‑
ment blood banks. The major objectives of the work‑shop, were to teach these participants how to use the
10cally developed reagent and to re‑emphasized theto oppose to our final goal to make a reagent withdomestic materials. For the reason mentioned above,
we had to change our objectives and intended to investi‑
gate the feasibility of use of antibodies raised in guinea

pigs, rabbits and sheep which are available locally in
Kenya. We could get good results from purified anti‑

public health importance of hepatitis B. It is as a resultof such research findings that strategy for the preventionof post‑transfusion hepatitis B has established.

35 FOOD HABIT OF THE POISONOUS SNAKE YOUNG HABU,
TRIMERESRUS FLA VOVIRIDIS ON THE AMAMI AND TOKUNOSHIMA ISLANDSHIROSHI SUZUK11 AND EIICHI NAKAMOT02
Department of Virology, Institute of Tropical Medicine,

Nagasaki University* and Amami Habu Center'

Natural food habits of the poisnous snake young

latta guttigera were observed. On the other hand, in the

Habu, Trimeresurus favoviridis on the Amami andTokunoshima Island 78% warm‑blooded animals as

Tokunoshima Islands in Japan were surveyed in 1991 to
1992. 458 males, 353 females in the Amami Islands and536 males, 375 females in the Tokunoshima Island were
examined.

Rodents especially Watase's shrew, 21% as Reptile

Food of young Habu belong in Mammalia, Aves,
Reptilia and Insect of 9 species. In the Amami Islands

72% cold‑blooded animals as Reptile, Ryukyu little
brown skink, Lygosoma pelloplearum, Ryukyu green
grass lizard, Takydromus smaragdinus and Gecko,
Gekko sp. mainly Ryukyu little brown skink, 26% as

Ryukyu little brown skink, Ryukyu green grass lizard,

Gecko and Ryukyu rice‑paddy snake, Natrix pryeri
pryeri and a bird, Zbsterops palpeblosa loochooensis.

In the case of the Tokunoshima Island in winterseason January to March 16 cases of Rodents and one
case of Reptile were found. It's mean that the young
Habu hunt prey in winter season too but in the Amami
Islands only one case were found.

Different of species and number of prey in bothRodents, Watase's shrew, Crocidura horsfieldi watasei

Islands that depend on distribution and number of natu‑

and Amami spinous country‑rat, Tokudaia osimensis

ral food inhabit in its.

osimensis and one case as Insect, cockroach, Rhabdob‑

74

36 THE REPRODUCTIVE CYCLE OF THE FEMALE HABUFUMIKO YOKOYAMA AND HIROSHI YOSHIDA
Department of Pathology Faculty of Medicme Kagoshima Unrversity

The reproductive cycle of the female Habu. Trimer‑prog<esterone stayed low. FSH in hypophysis was recog‑

esurus favoviridis was studied. Vitellogenesis started in

nized by immunohistological staining in October,late April, and progressed in parallel with a striking
increase of serum estradiol. The genital organs and thealthough we could not detect any rise in serum FSH.
LH in hypophysis was recognized from July to October,liver showed characteristic changes in the estrousand serum LH rose in July. It is known that the injec‑tion of human FSH produces vitellogenesis in nonmam‑
malian vertebrates. So vitellogenesis and other active
changes in estrus need not only gonadotropin but also

period. Mating occurred in late April, too. Both ovula‑tion and parturition happened early in June, when thelevel of estradiol fell abruptly. After parturition no
sperms were found anywhere in the genital tract except
for the infraepithelial alveolar glands of the transition

region. Immunohistological study by anti‑estradiol
antibody suggested that estradiol is synthesized in theadrenals. In comparison with serum estradiol, thefluctuation in serum progesterone was within a small
range. Serum progesterone rose slightly in spring, thenafter a slight decrease it rose again just before ovula‑tion. During late autumn and winter the level of serum

other factors, especially temperature for̲ poikilothermic

animals. The other pituitary hormones, GH, ACTH,
and prolactin also exhibited interesting seasonalchanges.
Our results show that the most suitable time forhabu‑hunting to reduce the danger of Habu‑bite is
before mating, from March to early April in Amami
Islands .

37 AN EPIDEMIOLICAL STUDY ON THE SNAKEBITES IN GUANGXIZHUANG AUTOMOUS REGION, CHlNA IN 1990

YOSHIO SAWAI*, YOSHIHARU KAWAMURA*, MICHIHISA TORIBA* AND
NAIPlNG WANG'
Japan Snake Institute* and Guangxi Medical College'

The data on 974 cases of snakebites in Guangxi
during the year 1990 were collected. The species ofvenomous snakes and the rate of occurrence of theirbites were Naja atra ( 27.4%), Bungarus multicinctus

during daylight hours from 6 a.m. to 6 p.m. mainly infields and mountains, while bites in dark hours mainly
occurred in residences and on roads. 94% of bites were

(8.4%) , B. fasciatus (2.7,%) , Qphiophagus hannah (1.2%)

sixties, and bites in males were two and a half times as

Trimeresurus stejnegeri or T. albolabris (20.9%), T.

frequent as those in females. 21% of the total bites

widely distributed between the ages from teens tomucrosquamatus (13.4%), Deinagkistrodon acutus

occurred during handling or catching the snakes, and the(6.2%), Vipera russelli (5.5%), Azemiops feae. T. jer‑
donii and sea snakes (0.8%) .

rate was very high in N. atra (50% ) and O. hannah(92%). Fatal cases were 23 (2%) and higher fatality
rate were by O. hannah (46%), B. multicinctus (10%)

During warmer months from April to October, 88%of bites occurred. 18% of the total bites occurred inresidences, 18% were on roads, 26% were in agricultural
fields and 17% were in mountains. 56% of bites occurredand B. fasciatus (8%). That of N. atra was rather low(0.7%). Most of the bites were treated by traditional
Chinese herbal medicine.

75

38 EFFECTIVENESS OF PROTEASE INHIBITION IN SEVERE MAMUSHI BITEHIROSHI WATANABE , TSUYOSHI NAGATAKE*, KEIZO MATSUMOTO1TASUKU SAKAMOT02, NAOTO RIKITOM12 AND EIJI HIRANO'
Department of Internal Medicine, Institute of Tropical Medicine*and Aino Kinen Hospital'

In Japan we often see Mamushi bite. It is estimatedthat Mamushi bite are 3,000 cases per year. Most ofthem are slightly or moderately cases, but rarely we canexperience severe cases with DIC or multiple organ
failure. Here we report 3 severe cases improved quickly

after the early administration of protease inhibitor(FOY). First case was a 78 year old male. Afterdata was GOT 326, LDH 1,920, CPK 7,074, WBC 22,000,
and hematuria. We administrated FOY one day after
admission, and the course was good. Third case was a
44 year old male. The data on admission was GOT 71,
LDH 417, CPK 2,224, WBC 18,900. In this case also thecourse after administration of FOY was good. Mamushi

blood pressure. We started FOY 5 days after admission

venom include several protease, which destroy blood orcause muscle necrosis. If we̲̲administer protease in‑hibitor (FOY) early, we can inhibit the action of thewhen we found sendency of DIC. He had acute heart

protease and also prevent DIC. Therefore we might

failure and paralytic ileus as complications, but thecourse was good after administration of FOY. Secondcase was a 74 year old female. On admitted laboratory

expect effective treatment by protease inhibitor (FOY)

Mamushi bite he had liver and renal disfunction, and low

in severe Mamushi bite.

39 THE BOX JELLYFISH ( CHIROPSALMUS Q UADRIGA TYS) STlNGS IN OKlNAWA
YASUTETSU ARAKI , YASUHIRO TOMIHARAl, KUNIKI SHIMOJll AND

KEISUKE FUKUMURA2
Okinawa Prefectural Institute of Public Health* andThe Environmental Research Center, Okinawa Prefectural Foundation'

There has been no official report on the stings by theextremities of the body in August 1961.

jellyfish in the Ryukyu Islands. But it has been well

The Chiropsalmus quadrigatus are distributed

known to the general islanders that the stings are caused

around the whole Okinawa Islands, including Okinawa

by several kinds of the jellyfish, of which Yamaguchi(1982) pointed out the box jellyfish, Chiropsalmus qua‑

Main ,･ Island, Miyako Island, Ishigaki Island anddrigatus as chief assailants.

When stung, people feel a keen burning pain, getting
a welt on the skin touched by their tentacles. In serious
cases, the skin develops necrosis and discoloration, Ieav‑

The following are the facts revealed by the investi‑

gations into 67 cases of the stings by Chiropsalmus
quadrigatus from 1956 to 1991: ‑The stings occurred from June to September, withlriomote Island.

ing their traces for a long time. In some cases, condi‑
tions were so serious that the victims' heart and respira‑August as a peak, showing 33 cases (50.8%) . The stings
took place within 5 meters' distance from the seashore,
totalling a half (29 cases) . The degrees of conditions
were mostly slight for 46 cases (70.8%) , medium for 11

tion failed. This means that in the case of an infant asting may easilylead to very serious conditions.

cases (16.9%) and serious for 7 cases (l0.8%). There
was one death which occurred about one hour after thethan 50 cm. Being transparent in color, they are rarely

accident when a boy, age 13 was stung in the lower

When grown up, this box jellyfish become big,measuring lOcm, with their tentacles reaching more
recognized by the swimmers before they are stung.

76

40 INTEGRATED CONTROL OF JAPANESE ENCEPHALITIS VECTORS:‑AN INQUIRY WITH MATHEMATICAL MODEL‑MOTOYOSHI MOGI
Department of Microbiology, Saga Medical School
A main vector of Japanese encephalitis (JE) in east

(without overlapping effects) measures does not lower

and southeast Asia is a mosquito, Culex tritaeniorhyn‑chus. Control of this species is quite difficult due totemporally and spatially heterogenous and vast larval
habitats (rice fields and associated irrigation/drainage

cost‑effectiveness thus is preferred, (4) Relative
effectiveness of measures changes with the initial condi‑
tions; therefore baseline data for each locality is essen‑

systems) , high reproductive potential, wide fiight range,that locality, (5) with regard to measures against adultexophily, and, in some localities, insecticide resistancevectors, relative numbers and attractiveness among
hurnans, swine (and also other domestic bloodmeal

acquired as a byproduct ,of agricultural chemical appli‑

cation. To explore the possibility for reducing humanrisks to be infected with JE virus, a JE transmission

dynamics model involving swine (virus amplifyinghost), humans and a vector mosquito was developed. In
this model system, vector abundance is influenced byavailability of bloodmeal hosts, either swine or humans
as well as larval survivorship which includes both den‑tial for adoption of measures being more effective inhosts such as cattle if exist) are especially importantfactors influencing the relative effectiveness of eachmeasure, (6) Larval mortality from a indigenous preda‑
tor complex is a hidden factor infiuencing the level ofhuman risks, and (7) Changes in predation mortality
within lO% may still enough to cause substantial change
in the level of human risks. Though it would be difficult

sity‑independent and density‑dependent components.

to exterminate virus amplification among swine by

Human risks of JE virus infection can be evaluated with
infective mosquito density multiplied by the probabilityof biting humans. Model consequences suggest; (1) Inte‑gration of multiple measures can substantially reduce
human risks, even if their effectiveness is solely not
sufficient, (2) Effects of each measure may overlap withthat of others, (3) Combination of mutually independent

reducing the basic reproductive rate below unity, it
appears possible to reduce human risks substantially by
a combination of interventions appropriate and accept‑
able to each area. As a basic strategy for integration ofmultiple measures against mosquito vectors with wide
flight ranges, a concept of "horizontal integration" isproposed.

41 A ROLE OF MIDGUT IN THE SUSCEPTIBILITY OF MOSQUITOES TOCHIKUNGUNYA VIRUS

HIROSHI YAMANISHll, EIJI KONISH12 AND TAKEO MATSUMURA2
Kobe Gakuen Women's Junior College* and Department of Medical
Zoology, Kobe University School of Medicine'

Chikungunya virus concentrations in the head/tho‑rax, midgut and other abdominal parts were measured
to compare virus multiplication in the mosquito Culex

In the Oahu strain of Ae. albopictus, all the midgut
specimens were positive for CHIK virus by the 7th day

triiaeniorhynchus. Aedes aeg)pti and two strains of Ae.

with BHK 21 cells. In Cx. tritaeniorhynchus, CHIK virustion, CHIK virus was detected in the other parts thanthe midgut. For these experiments, a role of midgut inthe susceptibility of mosquitoes for CHIK virus wasdisappeared from the midgut by the 2nd days after

thought to be important. It was discussed the factors forfeeding. In Ae. aeg pti, CHIK virus was observed in 12%of the midgut for 2 weeks after infection. In the Hyogo

the susceptibilty in the midgut were digestive juices andalbopictus (Hyogo and Oahu strain) by plaque assay

strain of Ae. albopictus, CHIK virus was observed in

60% of the midgut for 2 weeks. CHIK virus was notdetected in the other tissues on the 4th day after feeding.

after infection. On the 7th and the 14th day after infec‑

peritrophic membrane.

77

42 HOST PREFERENCE OF ANOPHELES MINIMUS
YOSHIO TSUDA, MASAHIRO TAKAGI AND YOSHITO WADA
Department of Medical Entomology, Institute of Tropical Medicine,

Nagasaki University

The host preference of vector mosquito is one of theimportant parameters determining the relative impor‑tance of vector mosquitoes in disease transmission,
though it is not easy to quantify the degree of theirpreference to man. In the classic method examining
host preference of vectors, two kinds of animal baits

were exposed to mosquito feeding and compared thenumber of attracted mosquitoes to the baits. Thismethod gives us an information about the host prefer‑ence but a new analytical method have to be developed
to quantify the host preference through the comparisonof the number of attracted mosquitoes between thebaits. A new index of host preference, Hp, was definedby the following equation as the probability of mos‑quitoes feeding on one kind of animals when two kindsof animals are available for blood feeding;and Mh are the number of mosquitoes attracted to thetwo kinds of animal bait.

Using the index, host preference of Anopheles
minimus in Northern Thailand and Ishigaki‑jima popu‑
lations were compared based on the results of baitcollection derived from Chiangmai in November, 1990
and Ishigaki‑jima in July, 1992. Because of the geo‑
graphic isolation and different history of mosquito con‑trol in these two areas, Ishigaki‑jima population was
expected to show lower preference to man than North‑ern Thailand population. The result of our analysis
showed that the lower preference to man in Ishigaki‑
jima population will be expected only when the follow‑
ing inequality holds; kw/k>40, where k and kw are theefficiency of sweeping collection and double net collec‑
tion, respectively.

Hp=B Mh/(H Mb+B Mh) where B and H are thenumber of animals used in the bait collection and Mb

43 OCCURENCE OF VECTOR MOSQUITOES OF JAPANESE ENCEPHALITIS INNORTHERN THAILAND IN RELATION TO THE RICE CULTIVATIONMASAHIRO TAKAGll, YOSHIO TSUDAl, YOSHITO WADAI ANDWANNAPA SUWONKERD2
Department of Medical Entomology, Institute of Troprcal Medicme
Nagasaki Universityl and Malaria Center 2, Department of Communicable Disease Control,
Ministry of Public Health, Thai Government2

As a part of the epidemiological study on Japanese
encephalitis in Thailand, we conducted a monthly quan‑titative field survey on the vector ecology and habitat
conditions of the vectors. A variety of rice fields, whichwere the main habitat for vector larvae, was examinedon the density and the species composition of larvae, theprevalence of water, the water quality and the height ofrice, or grasses.

fields. Cx. vishunui may have been underestimated its
role for transmission of the disease because the species

is hardly distinguished from Cx. tritaeniorhynchus byadult specimens, while Cx. vishunui was so common that
it was the most predominant in some rice fields in our
survey tergetted to larvae which were easily identified
the species.

The larval density was apparently high in the twoAmong six species which were reported as thecropping rice fields, and the initiation time of increase

vectors, three species, Culex tritaeniorhynchus. Cx. vi‑

nearly coincided to ploughing for the next transplanting.

shunui and Cx. gelidus were incriminated. The otherthree species, Cx. whitmorei. Cx. pseudovishunui and Cx.

On the other hand in rice fields of the single cropping,
the density was lower than the two cropping areas. The

fuscocephala, were not often encountered in our study

seasonal prevalence of adult populations examined at

78

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Type

A

and

B

SHR

SHR−C，WKY−C

and

WKY−H，BWvaluesofTypeAweresigni且cantly

months1er（p＜0．01）than

those

old

M），and117±4mmHg

and234±3g

in

heat−

acclimated WKY（WKY−H，N＝7，4．1M），respective−
ly．And inType B ofWKY，valuesof BP and BWwere
as follows：143±2mmHg and349±6g inWKY−C（N＝handling（3）and5，4．6M）；115±5mmHgand314±7ginWKY−H（N＝8，In

4．3M）；127±4mmHg and324±15g in control rats
exposed to themoneutral condition（WKY−N，N二6，

acclimation

4．OM），respectively．Valuesofnormotensive

WKY−C

higher（p＜0．05）thanweresigni且cantly

BP

in

Type

A

and

B

cardiovascularpreweanling

a

of

those

this

of

control

of

a

in

in

Type

systemenviro㎜ental

study，BP

mild

WKY．Andofrearingbyweredevelopment

of

SHR

susceptible

toisnomlotensive
not

both

Type

A

hypertension

was

induced

WKY（1）．On

and

the

sma1−

B．The

innuences，云6．avaluesthanof（Mean±S．E．）of BP and BW were134±3mmHg and
310±7g in cold−acclimated WKY（WKY−C，N＝6，3．9

A

BP

cold−

mother（2）．

reduced

Type
by

B

repeated
by

of

cold

heat−

SHR，though

exposureotherhand，in

SHR

in

and

WKY，valuesofBWinheat−acclimatedratsweresma1−

inWKY−H．InWKY，therewasnosigni且cantdi仔erence

1er

of

cold−exposed

betweenBPvalues

of

Type

A

solvedvalues

of

BP

and

BW

were179±5mmHg

45

and

B．In

1NHIBITION
JIA−MING

type

A

of

SHR，

and318±7g

of

LEE1，MITsuo
Environmental
of

KosAKA1，KElzo

isactivatedby

LPS

development

theenvironmental

of

in

the

of

blood

to

remains

to

be

SHR

is

releasesitininfluences．

OF

MATsuMoTo2AND

and

Department

Medicine，Nagasaki

Cellular

University

rats．It

hypertension

YAMASHITA3

Physiologyl

Tropical

Department

Nagasakimacrophage

to

the

OF IL−1SERECTION AND PRORIFICATION
MACROPHAGE DUE TO HEAT LOAD

Medicine2，Institute

The

those

why

resistant

SHuN−ICHI
Department

than

of

University

IntemalandPhysiology，SchoolofMedicine

inducesynthesisofendogenous

pyrogenand79

into the blood, and fever is caused. Interleukin‑1 (IL‑1)

is the principal substance among endogenous pyrogens,which causes varient physiological regulations including

a fever respdrise. IL‑1 stimulates organum vasculosum
laminae terminalis (OVLT) , which exists on the sidewall of third ventricle in the brain and causes the release

supplemented with 10% FBS. The result of methyl ‑[,H]‑thymidine incorporation in' RAW 246.7 cells
showed that the proliferation of the macrophage wassuppressed by a heat load of 39'C for 2 hr. Enzyme‑Iinked immunosorbent assay (ELISA) showed that theactivity of IL‑1 secretion induced by LPS was alsoof prostaglandin E2 (PGE2) there. PGE2, a cascade of

suppressed by heat load. Suppression of activities of thearachidonic acid, reaches to preoptic area and anterior
hypothalamus (PO/AH) , causes a reset of the setpoint,

macrophage including proliferation and secretion sug‑
gent that negative feed back loops exist where the end

and thus triggers a fever response. The reaction as
follows is important during bacterial infection: LPS

product, heat, may act back on the macrophage. The‑macrophage‑IL‑1‑PGE2‑fever. One might wonderin the macrophage was detected by Western‑blot andwhy even extremely high fevers seldom exceed 42'C. It
is postulated that there is a self‑limiting mechanism,
such a"s a negative feedback loop. On the other hand, theheat shock protein (hsp 70) can be induced by heatstress. However, hsp 70 relates to a febrile response or

induction of heat shock protein (hsp 70) by heat shock
Northern‑blot analysis. In U‑937 cells, the increase ofhsp 70 band appears to be related to the extent ofinhibition of IL‑1 secretion.. The physiologicalsiguificance of induction of hsp 70 in macrophage areassumed as follows: I ) To prevent heat denature of pre‑rebosome from heat shock during heat stress 2) To

not has been‑･ seldom discussed. The present study,
therefore, investigated influences of heat shock on
macrophage proliferation and IL‑1 secretion, studied
the induction hsp 70 in macrophage, and examined thecorrelation between them. RAW 246.7 cell and U‑237

negative feedback loop is formed and result in a subsid‑

cell were used and cultured with RPMI 1640 medium

ing of a fever.

suppress the biosynthesis and secretion of IL‑1 by meanof combination of heat shock transciption factor(HSTF) to IL‑1 gene on the chromosome, thus, a

46 ANALYSIS OF MICRO‑ENVIRONMENT ON SWEAT SKIN COVERED BY
THERMAL SWEATlNG OF THE SKIN COVERED BY CLOTHING MATERIALKlNUYO OTOMASU, MITSUO KOSAKA, NoBU OHWATARI, MASAKI YAMAUCHI,MASAKATSU MOTOMURA, TAKAAKI MATSUMOTO, KATSUHIKO TSUCHIYA,JIA‑MlNG LEE AND GUO‑JIE YANG
Department of Environmental Physiology,
Institute of Tropical Medicine, Nagasaki University

In order to clarify the effect of different clothingmaterial on the micro‑environment between clothes andskin, analysis of thermal sweating was investigated byusing the sweat capsule method. Changes in the micro‑
environment induced by sweat capsules, clothes and skinsweat, were detected by hygrometer cambined with acomputer and DC recorder. Moisture changes in the
micro‑environment of the sweat capsule may depend on(27'C, 60% rh) , subjects were submitted to a 43'C water
bath heat load to bilateral lower e

tremities for 30 min.

Sweat volume and initial indrease‑rate of thermal

sweat in the medial portion of the chest due to 43'C
water bath heat load were significantly higher than thelateral portion of the chest. There were no significant

changes among the three different kinds of clothingmaterial on sweat volume, nor were there any effects ofthe following three factors such an absorption, penetra‑

a different setting mode in the order of clothing materialtion and evaporation of wet clothing material on thesweating skin. Four sweat capsules connected to dry N2
Gas (1 Iiter/min, capsule) were fixed on the anteriormaterial was in the order: nylon > silk, and cotton > silk.

on sweat volume. Sweat onset time for each clothing

experiments using 6 male subjects were performed.

This may be attributed to the difference in absorption
and penetration among each clothing material.
Recovery time of sweat‑curve after the cessation ofheat load was siguificantly longer in the medial portion

After a 10‑20 min rest in an environmental control roomof the chest than the lateral portion of the chest, whichchest, each covered by a small piece of different kinds ofclothing material such as silk, cotton and nylon. 24

80

could depend on differences in sweat volume in these
portions of the 'chest. Recovery time, however, wassignificantly different kinds of among three different
clothing material and the results obtained was in theorder of: cotton > silk > nylon. In the present study,

analysis of moisture changes caused by clothing mate‑rial was analyzed at the level of micro‑environment,‑and
the results obtaiped will be useful for analyzing the bestmode of daily wear that is optional for human an body
physiology.

47 STUDY ON MECHANISMS OF HEAT ACCLIMATIZATION DUE TO SWEATINGMITSUO KOSAKA , TAKAAKI MATSUMOTO , MASAKI YAMAUCHI*
KATSUHIKO TSUCHIYA , NoBU OHWATARI , UnoM BOONAYATHAP'
CHUCHEEP PRAPUTPITTAYA2 AND ANCHALEE YONGSIRI'
Department of Environmental Physiology, Institute of Tropical

Medicine, Nagasaki University* and Department of Physiology,
Faculty of Medicine, Chiang Mai University, Thailand'

Recently, most theories consider that central andperipheral inputs jn thermoregulation interact at a neu‑

ral level in the hypothalamus of which effector mecha‑
nism indicates little or no increase in heat acclimatedanimals (habituation phenomenon) . In this study, there‑
fore, to clarify the mechanisms of heat acclimatizationof permanent residents in tropical climate, heat toler‑ance and sweat response to heat load of tropical subjects

in Chiang Mai and temperate subjects in Nagasaki werecompared under identical conditions.

Male students in Chiang Mai (n=10) and in
Nagasaki (n=10) volunteered in this study. Mean
annual air temperature is reported to be 16.6"C incapacitance hygrometer‑sweat capsule method. Change
in oral temperature, sweat onset time and local sweat
volume were compared between Japanese and Thai.
Initial oral temperature (36.76 0.11'C in Japanese,
36.71 0.23'C in Thai) was identical, and no sweat wasobserved before heat load. Mean sweat onset time (9.3d:
2.1 min chest in Japanese, 16.6d:5.6 min chest in Tha.i)

was significantly longer and local sweat volume (10.19

5.00 mg/cm2, chest in Japanese, 1.39 0.91 mg/cm2,
chest in Thai) was siguificantly smaller in Thai subjects

than Japanese, however, oral temperature (37.18
0.32'O of Thai subjects was kept slightly lower thanoral temperature (37.42'Cd:0.lO'O of Japanese even in

Nagasaki (32'44'N, 129'52'E) and 25.9'C in Chiang Mai(18'47'N, 98'59'E). The Thai subjects were a little

30 min heat load. Sweat volume on the abdomen was

shorter and slightly leaner than the Japanese. Heat load

the contrary, sweat volume on the chest was larger thanthat on the abdomen in 7 of 10 Japanese subjects. These

was applied on the legs by immersing into hot water(43'O for 30 min in the room at 26.6'C and 33% rh.

larger than that on the chest in 9 of 10 Thai subjects. On

results suggest that heat tolerance of tropical subjects is

Sublingual (oraD temperature was measured with adue to a more efficient evaporative the greater heat loss

thermistor and local sweat rate was measured with abrought about by their long term exposure to heat.

48 COLD TOLERANCE OF HYPOTHERMIC SYRIAN HAMSTER DUE TO ACUTE
COLD EXPOSURENoBU OHWATARI, JIA‑MlNG LEE, MASAKATSU MOTOMURA AND MITSUO KOSAKA
Department of Environmental Physiology,
Institute of Tropical Medichne, Nagasaki University

Syrian hamster is a hibernator which is possible tolive in a low core temperature at 5‑8'C during a hiberna

hibernation. Syrian hamsters were submitted to thetion in winter. Therefore, this study experimented tocompared with those of Wistar rat. Temperatures in
the abdominal cavity (Tab) , abdominal skin (Tabs) ,clarify an ability of cold tolerance in the stage of non‑acute cold exposure at O'C and the results obtained was81back skin (Tbs) and brown adipose tissue (Tbat) were
measured with a thermistor thermometer every minute.
Respiratory rate and ECG also were recorded with awith Tab of Wistar rat during the cold exposure, and thechanged to high amplitude with decreasing of Tab. In
rat, ECG pattern of high amplitude and low frequency
appeared again after ECG temporally disappeared at
26.45'C of Tab. But the disappearance of ECG was notobserved in Syrian hamster.
The difference of the back skin and the abdominal

minimum Tab (6.82'O in Syrian hamster was lower
than 15.14'C in Wistar rat. Tab of Syrian hamster

skin insulations suggests that the posture to curl itself
up in cold environment is useful for a protection against

data recorder.

Tab of Syrian hamster decreased quickly compared

increased just after the stop of cold exposure and Syrian

a heat loss from body surface. The insulation of skin inhamster survived, but Wistar rat could not recover

Wistar rat was better than that in Syrian hamster. It
was well reported that the metabolism of Wistar rat

though Tab of Wistar rat slowly increased to 19.78'C.
The insulation of back skin is better than that of

abdominal skin in both animals as ̲ a result of thedifferences of Tabs and Tbs from the temperature of

was higher than that of Syrian hamster in summer.
Though Wistar rat is powerful compared with Syrian
hamster from views of the insulation and the heatcold exposure, and the insulation of the skin in Wistar
rat was superior to that in Syrian hamster.

production, the ability of cold tolerance in Syrian ham‑ster ‑was superior to that of wistar rat during hypother‑

Respiratory patterh changed eupnea to bradypnea
during hypothermia in both animals. Heart rate of
Syrian hamster changed normal range to bradycardia
characterized by long interval time and ECG patternmia. Syrian hamster of hibernator possesses high abilityof cold tolerance in hypothermia not only in hibernation
but also in arousal stage.

49 A SURVEY OF INTESTlNAL PARASITIC INFECTION IN KOK TRAPCOMMUNE, CAMBODIA; USING THE AGAR PLATE METH()DKAORI KOGA , SHIRO KASUYA* AND HIROSHI OHTOMO ,'Department of Parasitology, Gifu University School of Medicine*and Jikei University School of Medicine'

Recently, the agar plate method has been shown tobe successful in detecting Strongyloides stercoralis infecal materials, while traditional methods have beenreported to be unreliable. We have been reporting that

The positive rate of intestinal parasites seen among

100 villagers was 82%. The most common parasite washookworm (71%) followed by Strongyloides (19%),

coutries based on results of our previous studies in
Chiang Mai Province, Thailand. Moreover, we reported

Ascaris lumbricoides (3%), Trichuris trichiura (2%),
Giardia lamblia (2%), Entoamoeba coli (1%) and Enterobius vermicularis (1%) . Out of 71 cases of hookworm‑
positive, Necator americanus was found in 11 cases,
Ancylostoma duodenale in 16, and one was mixed‑infect‑

previously that this method was revealed to be sensitiveed.

the agar plate method is very efficient, not only for its
reliability but also for its field applicability in developing

enough to detect Stongyloides even when only one worm
was present in the fecal sample. Since prevalence rateof Strongyloides among villagers in Huey Keaw Village,
Chiang Mai Province was 34%, much higher than previ‑
ous surveys performed without the agar plate method, it
is suggested that global prevalence of Strongyloides
infection is much higher than the present estimation.
In this study, stool examinations including the agar

plate method for villagers in Kok Trap Commuhe,
Kandal Stung District, Cambodia was performed todetermine the present state of parasitic infections in thevillage .

Cambodia has been reported to be sufferd from war.

We can rarely find the data about epidemiology orhealth situation in Cambodia. It had been presumed thatpeople possess many kinds of intestinal parasites, but

the results showed the parasites except hookworm andStrongyloides is not so prevalent unexpectedly.

82

50 AN EPIDEMIOLOGICAL STUDY ON STRONGYLOIDES INFECTION ON

MlYAKO ISLAND OF OKINAWA PREFECTURE, LOOKING FOR ANY POSSIBLE
RELATION BETWEEN INFECTION AND FARMING ACTIVITY
RYUJI ASATO1, TAMIKI ARAKAK12, TSUYOSHI IKEMOT03,

MASAAKI SHIMADA4 AND HACHIRO SAKIYAMA5
Okinawa Prefectural Institute of Public Health*, Department ofBacteriology, School of Medicine, University of the Ryukyus',

Okinawa Preventive Medicine Cooperation', Department of
Parasitology and Tropical Public Health,
University of Occupational and Environmental Health' andOkinawa Prefectural Miyako Health Center*

We have been carrying out surveys into the preva‑

human manure and whether or not they went barefoot inlence of Strongyloides infedion in almost all regions of

their fields. The proportion of infected cases found for

Okinawa since 1988, and have previously reported thateach behavioral factor is shown for both sexes. Fromthese results, it seems probable that engagement inalmost all Strongyloides carriers are over the age of 40

and that there is a marked regional difference in preva‑

agriculture itself was not a major risk factor for Stron‑

lence. A preliminary questionnaire survey was conduct‑
ed on Miyako Island, into infection risk factors.

gyloides infection on Miyako Island. Further study

The questions were whether people had everalong different lines is indicated to determine the rele‑vant factors in the spread of this infection.

engaged in farming or not, whether they had ever used

51

EFFECTS OF FLUBENDAZOLE AND MEBENDAZOLE AT A LOW DOSE ON THE

GROWTH OF ANGIOSTRONGYLUS CANTONENSIS IN RATS
JUN MAK11 AND SUSUMU KANDA2
Department of Parasitology, Kitasato University School of Medicine*and Branch Hospital Pharmacy, University of Toky02

Many human cases infected with Angiostrongylus
cantonensis have been found in Taiwan, Thailand andautopsied 8‑10 weeks after the medication. Almost no
worms were recovered from the rats medicated 3 days

the Pacific islands with a small number of cases in someparts of tropical, subtropical or temperate zones includ‑post‑infection. The larvicidal effects of the drugs ad‑
ministered 10 days post‑infection were not so high as
those 3 days post‑infection. However, the larvae still
surviving in the rats medicated 10 days post‑infection

ing Cuba and lvory Coast (Hung and Chen, 1988).
Despite the infection, no suitable chemotherapy hashitherto been established. Though benzimidazoles suchas mebendazole, flubendazole and albendazole are prom‑

were found to have been inhibited siguificantly fromtheir growth in length, width and weight except theising in killing A. cantonensis in human cases, there still

length of the larvae in the rats given mebendazole. An

remains a problem to overcome: any adverse effects forwhich the worms drastically killed might be responsible

inhibition from their growth was also demonstrated
with the observation that no first‑stage larvae (L1)

(Maki and Kanda, 1992). The present communication

were released in the faecal pellets from the rats medicat‑

reports effects of flubendazole and mebendazole at a low
dose on the growth of this nematode in rats.

ed 10 days post‑infection and examined just prior to the

These benzimidazoles were each administered at 10
mglkg to rats harbouring the developing larvae 3 or 10

autopsy, at which L1 were released from non‑medicatedrats. On the other hand, when the drugs were adminis‑
tered 10 weeks post‑infection, no effects of the drugs

days post‑infection, or to rats habouring the adult

were seen in the number, body size and weight ofworms 10 weeks post‑infection. A11 the rats wererecovered worms and Ll release. It was reported that a83

higher dosage in total was needed to suppress L1
release. Flubendazole at 10mg/kg/day for 3 con‑secutive days reduced drastically the number of L1

the drugs than the adult worms. The symptoms inreleased in the faecal pellets about 6 days after the last

Flubendazole and mebendazole seem to be useful for the
inhibition in the growth of this nematode unless thedrugs are administered too late.

dosing (Maki, 1991). It was confirmed in the present
study that the developing larvae are more sensitive tohuman cases are manifest usually at least one week
after this nematode infection (Punyagupta et al., 1970) .

52 ANTICESTODE EFFECTS OF GASTROGRAFIN
TAKEO MATSUMURAl, MASAHARU NAKA02, EIMAN M. ZYTOONl,ATSUKO SAITOl, SHINSUKE MORIMOT03 AND SUSUMU SAEK13
Department of Medical Zoology , 2nd Division. Department of Internal

Medicine', Kobe University School of Medicine

and Kobe Teishin Hospital'

Cestodiasis is now an important parasitic disease incompared with those with 0.85% NaCl, Gastrografin,

Japan, having been imported from the developing coun‑

RPMI‑1640, or fetal calf serum, the four controls. Fivetries. Gastrografin is often used clinically as a vermi‑

proglottides were grown in each medium at 37'C in a
C02 incubator. Every 24 hr, the response by movement

fuge. The treatment is simple, and cestodes are living
when they are excreted. Therefore, this drug is recom‑
mended for use in studies of the morphology, physiology,

and immunochemical characteristics of cestodes. The
anticestode mechanism of the drug is not known. We
studied the effect of the three main constituents of
Gastrografin on cestodes by external cultivation of a
Taenia saginata excreted in its entirety by a female
patient. Gravid or mature proglottides were washedwith a mixture of RPMI‑1640 medium, penicillin (400‑500 units/ml) , and amphotericin B (30 pglml) , and thenincubated in one of three media, supplemented with
NaOH, meglumine, or amidotrizoic acid. Results were

to being touched with a syringe was observed. Survivalin the different media was also recorded for each individ‑

ual, ‑and maximum survival time for each group wascompared. The media containing NaOH or meglumine
shortened survival. Each proglottid was examined
pathohistQlogically. Pathological changes were found in
the tegmentum and subtegumental structures and in thenumber and distribution of calcareous bodies in themedium with NaOH. The anticestode effects of
Gastrografin seem to arise from the constituents NaOH
and meglumine as well as from the high osmolarity andincreased intestinal peristalsis.

53 ANTI‑PHEX ANTIBODY, AS A SCREENING METHOD FOR
SUBCLlNICAL AMEBIASIEIICHI OKUZAWA, SEIKI KOBAYASHI, SACHIO MlURA AND

TSUTOMU TAKEUCHI
Department of Tropical Medicine and Parasitology,
School of Medicine, Keio University

In our previous study, we have demonstrated that
there is a significant difference in the antibody responses

anti‑CRAR IgG responses. Conversely, the sera isolated
from chronic amebiasis revealed a high titer of anti‑of the sera isolated from various stages of amebiasis

CRAR and a low titer of anti‑PHEX IgG responses.

patients on enzyme‑linked immunosorbent assay(ELISA) ̲using threetypes of Entamoeba histolytica

Therefore, to evaluate a utility of these ELISA methods
with three types of antigens as a screening test for theantigens. The sera isolated from acute‑phase amebiasis
revealed a high titer of anti‑PHEX and a low titer of

inhabitants in endemic areas for amebiasis, we appliedthese ELISA to the sera isolated from Indo‑China refu‑

84

gees with subclinical amebiasis.

weight substance has been identified as a maj or antigen

Seventy sera isolated from Indo‑China refugees,by Western blotting analysis of the PHEX antigen.

who were positive for E. ,histolytica trophozoites or cysts

Virtually all sera from the Indo‑China refugees reacted

in their stools, and fourty sera isolated from Japanese
healthy subjects, who were free from parasitic infections
and abnormal findings by periodic health check up, werewith such a molecule on Western blotting with PHEX
antigen though majority of these sera did not show

examined by serological tests including ELISA andWestern blotting. The cut‑off values of these three
ELISA methods were calculated by the mean absorban‑

sera except one isolated from the refugees, who dischar‑ce values of the sera from Japanese healthy subjects.

Approximately 70% of the sera from the refugees

from the refugees, who discharged non‑pathogenic
amoebae, showed negative on ELISA with the PHEX

revealed positive reaction on ELISA with the crude

antigen.

positive reaction on ELISA with the PHEX antigen. A11

ged pathogenic amoebae, were positive by ELISA with
the PHEX antigen. However, thirteen out of 15 sera

extracted antigen. The positive rates of these sera on

These findings probably suggest that improved

ELISA with the CRAR and PHEX antigens were 50%

ELISA with the PHEX antigen may be an efficient tool
for screening the asymptomatic subjects who are infected with pathogenic amoebae in endemic as well as non‑endemic areas.

and 30%, respectively. As also shown in our previous
study, there was no correlation between the ELISA titerusing CRAR and PHEX antigens. A Iow molecular

54 IMMUNODIAGNOSIS OF HUMAN SYSTICERCOSIS
II. RESULTS OF THE IMMEDIATE TYPE OF SKIN TEST REACTION
YOICHI ITO , KOICHI KOYAMA1, FUSAKO OSADAl, LI SHUHONGDU JUN2 AND LIANG JIAN‑AN2
Department of Parasitology, Kitasato University Schoolof Medicine* and Department of Parasitology, Noarman Bethune
University of Medical Sciences, the People's Republic of China'

Human cysticercosis is endemic in the northeast

or more in erythema was regarded as the positive.

area of China, although its mechanism of infection andepidemiologic status have not been clear yet. We have

ELISA was also performed in microtiter trays to 33 sera
of 54 hospitalized patients together with 13 control sera

planned to make a epidemiologic survey for humanof Japanese. Setting lowest positive limit at greaterthan 2 standard deviations above the mean of control
sera we established the minimum OD value required for

cysticercosis in an endemic area of Kirin Province,

China. Prior to make the survey, suitable im‑munodiagnostic systems for the screening of cysticer‑
cosis patients were examined. In this study we reporta positive titer. As the result of skin test 38 (86.4%) outof the 44 cases of cerebral cysticerei infection and 8

our initial attempts to evaluate a immediate type of skin(88.9%) out of the 9 cases of muscle cysticerci infection

test for the one of tools using with screening of patients.

showed positive reaction. On the other hand 17 (68.0%)

Extract from the scolex with cyst wall for the skin testout of the 25 cerebral cases and 7 (87.5%) of the 8and cyst fluid for the ELISA system obsained from themuscle of pigs naturally infected with cysticerci weremuscle cases were positive by ELISA. The mean OD
value by ELISA obtained from cerebral cysticercosis

used as the antigen. The skin test was carried out to 54

patients sera was lower ,than that from muscle cysticer‑

hospitalized cysticercosis patients defined with CT scancosis patients sera but no significant difference wasobserved.

at the Military Hospital in Kirin Province. The caseshowing 9 mm or more in wheal diameter and/or 20 mm

85

55 COLLAGEN SYNTHETIC ACTIVITY IN THE FIBROTIC LIVER OFS CHI S TOSOMA MANSONI‑INFECTED MICEMASANOBU TANABE, TUNEARI SEKIGUCHI, NOBUAKI KANEKO,
TAKASHI ASAI AND TSUTOMU TAKEUCHI
Department of Tropical Medicine and Parasitology,
School of Medicine, Keio University

To clarify the mechanism of liver fibrosis in schis‑tosomiasis mansoni, we conducted some biochemical

production in the liver slices was first demonstrated 49
days after infection and observed until 100 days afterinvestigations using experimental murine model infect‑

infection. Intraperitoneal injection of the crude extract

ed with Schistosoma mansoni. This communicationof egg granulomas to normal mice had no effect on theiractivity of hepatic collagen synthesis. In contrast, adeals with identification of the major sitof collagenproduction in the fibrotic liver and of some soluble

significant increase in the collagen production was

factor (s) which is responsible for the increased collagendemonstrated in the liver of mice treated with the crude

production in the fibrotic liver. Fibrotic liver preparedliver extract prepared from infected mice. However,from S. mansoni‑infected mice for 9 weeks contained 15‑

the addition of such a liver extract has no effect on thetimes more collagen than normal. Hepatic collagencollagen production by primary cultured hepatocytes.
On the other hand, the collagen production by primarycontent increased rapidly during the 50 to 80th days ofinfection, and then increased much more slowly. Col‑lagen fibers increased in the fibrotic liver primarily
localized in the egg granulomas. The collagen produc‑tion, as measu, red by the formation of labelled protein‑bound hydroxyproline, in the liver slices prepared from
infected mice increased 8‑times more than that of unin‑

fected controls. However, the collagen production of
the isolated egg granulomas was much lower than thatof infected liver. Such a high level of hepatic collagencultured fibroblasts was significantly stimulated by pre‑incubation with TGF‑beta or the supernatant fluid of invitro culture of egg granulomas.
These findings probably suggest that liver cells may
play a major role in the increased collagen synthesis in
the livers of mice infected with S. mansoni. Moreover,some soluble factor (s) is probably responsible for theincreased hepatic collagen production in murine schis‑tosomiasis mansoni.

56 NECROSIS OF PRIMARY HEPATOCYTES AROUND SCHISTOSOMA JAPONICUM
EGGS IN VITROTERUAKI AMANO
Department of Parasrtology, Yokohama City University
School of Medicine

The main pathophysiological changes in schis‑tosomiasis japonica and mansoni are induced with
inflammatory reactions around the eggs, which were
deposited in portal and mesenteric veins, and the secon‑

dary responses than the direct damages which were
induced by adult worms themselves. It is well known
that the immunological responses, especially cell mediat‑

ed immunity, are concerned with the granuloma forma‑tion around the deposited eggs into portal and mesenter‑
ic vein. In experimental murine model, the liver necrosis

and inflammatory respprlses around eggs were inves‑tigated at first. However, there are many unsolved

questions about mechanisms of granuloma formation
around schistosome eggs. There may be many possibil‑
ities about the causes and mechanisms of host‑parasite
relationship. The secretory substances of mature mir‑acidium may induce granuloma reactions as host's
defense mechanism.‑
In this preliminary experiment, the primary he‑patocytes were cultured with the matured schistosome

eggs in vitro . The morphological changes of he‑patocytes around the eggs were investigated. The
female worms, which were collected from the portal
vein of the schistosome‑infected mice at 8 weeks after

86

infection, were cultured for 36 hr in vitro . The produced

amethasone, apurocinin and antibioticS was exchanged

eggs were cultured in RPMI 1640 medium including lO%

each other days. The degeneration of hepatocytesaround schistosome eggs began from 4 days, but noinactivated FCS and antibiotics for 7 days. The primary
hepatocytes were collected from a rat's liver, which waschanges of other hepatocytes. This result showed some

perfused with MEM including collagenase IV. The

substances, which were secreted from miracidium,small pieces of liver, which was removed from body andcut with a scalpel, wete passed through sterilized gauze
and steel mesh. The cell suspension was centrifuged andother cells including Kupffer cells were removed. The
hepatocytes and schistosome eggs were co‑cultured inplastic dishes coated with collagen. The medium includ‑ing insulin, glucagon, epidermal growth factor, dex‑

might have cyiotoxicity to hepatocytes and that theliver necrosis around schistosome eggs might be first

pathophysiological change, not but immunologicalres ponses.

After this I will investigate the biochemical charac‑
teristics about the secretory substances of schistosome
eggs .

57 RELATION BETWEEN ANNUAL RAINFALL AND NUMBER OF
BULINUS GLOBOSUS, HOST SNAIL OF SCHISTOSOMA HAEMA TOBIUM,
IN KWALE, KENYASHIGEHISA HABE SHlNICHI NoDA KIYOSHI MAKIYA3, N.D. MUHOH04
AND YOSHIKI AOK15
Department of Parasitology, School of Medicine Fukuoka Universityl,

Department of Medical Zoology, Faculty of Medicine, Kagoshima
University', Department of Parasitology and Tropical Public Health,

University of Occupational and Environmental Health3
Kenya Medical Research Institute' and Department of Parasitology,
Institute of Tropical Medicine, Nagasaki University5

Snail surveys for schistosomiasis haematobia werecarried out twice each month at small rivers in Mwa‑
chinga and Mtsangatamu villages in Kwale, Kenya for
10 and 6 years, respectively. Thereupon, the relation
between annual rainfall and number of Bulinus globosus
were studied. Rainfall in this area generally followed
the typical bimodal pattern of the Kenyan coast, and had

a major peak during April to May and a small one in
November. Kadingo River which flowed into Mwachin‑ga Village dried up in the dry season. The streams in
Mtsangatamu Village flowed continuously throughout
dry seasons.

728 mm) . Snail numbers peaked generally in October toNovember and in January (before and after the shortseasonal rains) in Kadingo River and peaked in March
to April (beginning of the main rains) at the streams in

Mtsangatamu Village. There is no clear relation
between the annual rainfall and the number of collectedsnails in the rivers of both villages. In Kadingo River,the more rainfall during seven months (June‑Dec6inber)
after the main rains was, the more the number of snails

were. However, the annual number of collected snails
suppressed at the low level when the annual rainfall in

the preceding year was small (under 500 mm) and/or

The annual number of collected snails in Kadingo

total amount of the rainfall in former year except theRiver varied from 964 to 4,031 (av. 2,428) and the annual

main rains was less than 200 mm. In the streams in
Mtsangatamu Village, the annual number of collected

rainfall varied from 440 to 780 mm (av. 580 mm). In
some streams in Mtsangatamu Village, the annual num‑snails was at a low level when the rainfall after the main

ber of collected snails varied from 257 to 1,483 (av. 839)

one, consequently, the large number of snails were

and the annual rainfall varied from 496 to 914 mm (av.

collected in case of small rainfall after the main one.

87

58 ASSOCIATION OF OPISTHORCHIS VIVERRINI AND
HEPATOBILIARY DISEASES IN NORTHEAST THAILAND
MAKOTO ITOl, CHAWALIT KAIROJKUL2, TOMOYUKI SHIRA13 ANDNoBUYUKI IT03
Department of Medical Zoology* and Ist Department of Pathology3,
Nagoya City University Medical School and Department of Pathology,
Fuculty of Medicine, Khon Kean University, Thailand2

Epidemiological studies on Qt)isthorchis viverrini
infection in rural communities in Khon Kaen, Northeast
Thailand have shown the high prevalence and intensityof the fluke infection. The local people are infected byeatin g raw fresh‑water fish (Koi pla) which containmetacercariae of the fluke. The high incidence of
cholangiocarcinoma (CHCA) in the area has also been
noticed. In this study, we measured lgG antibody titers

to O. viverrini antigens by ELISA in patients with
hepatobiliary diseases to investigate association
between the fiuke infection and the disorders in the area.

The titers were indicated by absorbance value.

the titer was observed between CCLT and VTA.
Among the CHCA cases, the positive rate and theantibody titers of females with intrahepatic CHCA werelower than those of males.

Those observations showed strong association
between high antibody titers to O. viverrini antigens andgenesis of cholangiocarcinoma. Synergistic effects ofother factors such as intake of N‑nitroso compounds
contaminated food should also be considered to explain
the genesis of tumours especially in patients with low
antibody titers, which will reflect light infection of thePatients with cholangiocarcinoma (CHCA) showedsignificantly higher positive rate of the fluke infection(89.4%) and antibody titers (mean=0.35) than patientswith calculous cholecystitis (CCLT; 69.0%, mean titer =0.13) and victims of traffic accident (VTA; 42.9%, mean

59

titer = 0.10). No significant difference on the rate andflukes, as was suggested by Thamavit et al. (1987).
They showed that even a few O, viverrini infection
cause the genesis of CHCA in hamsters administeredwith subcarcinogenic dose of a N‑nitroso compound.

LEISHMANIASIS AND ITS TRANSMISSION MODE IN ECUADORYOSHIHISA HASHIGUCH11, MASATO FURUYA2, SHIGEO NoNAKA3
TATSUYUKI MIMOR14 AND YUKI ESHITA5
Department of Parasitology

and Institute for Laboratory Animals',

Kochi Medical School, Department of Dernratology, Faculty of Medicine, University of the Ryukyus3,
Department of Parasitological Diseases, Kumamoto University School of Medicine+ and
Department of Parasrtology, Kurume University School of Medicine5

Cutaneous leishmaniasis is a major public healthmania, besed on the isolates from different endemic

problem in the rural area of Ecuador. In the country the
first case of the disease was published in 1920 more thanareas of leishmaniasis in the country. Accordig to the

70 years ago. Since this period there have been various
clinical cases published in distinct regions of Ecuador.

results obtained to date, there are several types of leish‑

maniasis found in the endemic area corresponding to theWe have carried out epidemiological studies on the

Pacific coastal region: Leishmania panamensis. L.
guyanensis. L. amazonensis and L. mexicana. In the

disease in the country since 1982 and disclosed several

region of the Amazon L. braziliensis has been describedcharacteristics of the disease, such as geographicaldistribution, vector transmission, reservoir hosts andcinical forms. In addition, many details have been

and in the Andean highland L. mexicana and L. major‑
like parasites were found. Moreover, we recently de‑scribed a new species, L. equatorensis sp. n., isolated

clarified in reference to the species of the genus Leish‑from arboreal mammals living in an area endemic fdr

88human leishmaniasis. Therefore, in total there aremania strains were isolated from four iriahunalianseven species of parasitic agents which are thought to be

species, Choloepus hoffmani didactylus. Sciurus granaten‑classified thus far (Mimori et al., 1989; Armijos et al.,
1990; Hashiguchi et al., 1990, 1991).

sis. S. vulgaris. Potos favus and Tamandua tetradactyla
from the coastal regions, and from two, Rattus rattus
and Canis familiaris from the Andean regions. Most of
the isolates from humans, sand flies and mammalians
were already identified by molecular characterization,such as isoenzyme electrophoresis, monoclonal anti‑
bodies and indirect radioimmune assay and schizodeme
analysis of kinetoplast (k)‑DNA as mentioned above,

With respect to the sand fiies, we studied 15 endemicareas in nine different provinces. In total more than 40

species were found, from which at least 11 were newly
recorded in Ecuador. If we add to these species theothers which have already been reported, we have a
total of 56 species, of which 16 are anthropophilic andthus must study their behavior as vector agents of leish‑
maniasis. To date, three species, Lutzomyia trapidoi. L.
hartmanni and L. gomezi from the Pacific coastal low‑land, and one species, L. ayacuchensis from the Andean
highland, were recorded as probable vectors of leish‑
maniasis in Ecuador. As to the reservoir hosts, Leish‑

but some are at present being characterized (Co‑
workers: Drs. Eduardo A. Gomez L., Juan J. Alava P.,
Vicenta V. Coronel, Jose Rumbea G. and Hugo Jurado
S., Ecuador, and Ken Katakura, Yoshitsugu Masumoto,

Masato Kawabata, Hiroyuki Takaoka and Atsushi
Hosokawa, Japan) .

60 TRIALS OF LOW AND HIGH CONCENTRATIONS OF TOPICAL PAROMOMYClN

OINTMENT FOR CUTANEOUS LEISHMANIASISSHIGEO NONAKA*, ATSUSHI HOSOKAWA

AND YOSHIHISA HASHIGUCH12

Department of Dermatology, Faculty of Medicine,
University of the Ryukyus* and Department of Parasitology,

Kochi Medical School'

There are many forms of treatments for cutaneous

ment in 4, a definite improvement in 10, slight reaction inleishmaniasis. Recently, topical chemotherapy for

four and no reaction in four. Some patients with large
ulcerative lesions complained of a burning sensation
during the application of lO% paromomycin, while thosewith plaque or nodules type of lesion did not. The

cutaneous leishmaniasis has been reported, using par‑omomycin ointment in combination with methylbenzeth‑
onium chloride. In Ecuador, there is a report on topicaltreatment for cutaneous leishmaniasis using same prepa‑

ration of paromomycin ointment. In this study, we
undertook an evaluation of topical treatment for
cutaneous leishmaniasis employing two concentrations,
10% and 2%, of paromomycin ointment without methyl‑
benzethoniurn chloride. A total of 74 cutaneous leish‑
maniasis patients living in the village of San Sebastian(Ciento Tres) , Department of Manabi, Ecuador, who
agreed with informed consent were recruited for thepresent study. All the subjects continued their daily
activity during the treatment without hospitalization.

Follow‑up of the treatment was performed between
January and April, 1991. The treatment with 2% par‑omomycin ointment produced a marked improvement infive patients, a good reaction in 22, a slight reaction in 18

and no reaction in 10. When 2% paromomycin ointment

present topial applications to the lesions of cutaneousleishmaniasis produced an relatively good results. In
particular, almost complete healing of the lesions was
obtained in several patients by topial treatment withparomomycin

ointment alone. There have already been

few reports on the topical use of paromomycin ointment.
Paromomycin is usually used topically in high concen‑

tration such as 12.5%. Furthermore, it is used as anointment in combination with methylbenzethonium chlo‑
ride. We compared the effects between high (10%) and10w. (2%) concentration of paromomycin. In our prelim‑
inary study, some patients with large ulcerative lesions
rejected to use our ointment because of burning sensa‑
tion at the application of high concentratioh of theointment. In a few case, Iow concentration also causeda slight burning sensation as well as high one. However,the degree was so mild that the patients could continue

was applied to the skin, ulcers started to dry but theinduration tended to persist. The treatment with 10%

to use the ointment. We, therefore, selected a low

paromomycin ointment produced a marked improve‑concentration (2%) for large ulcerative lesions and a

89high concentration (10%) for dry and nodulous and/or
plaque‑type of lesions.

61 ACCELERATED TRANSFORMATION OF TRYRANOSOMA CRUZI FROMTRYPOMASTIGOTE TO AMASTIGOTE IN A LOW pH MEDIUM
M.R.A., SILVA‑TAHAT, TETSUO YANAGI AND HIROJI KANBARA
Department of Protozoology, Institute of Tropical Medicine,

Nagasaki University

The rate of transformation of Tr)panosoma cruzi
from trypomastigote to amastigote was accelerated in

low pH medium. To determine whether this enhanced
transformation follows its natural course, two eventswere investigated, namely: the ultrastructural changes
in the kinetoplast and protein analysis. For electron
microscopic studies, cells were collected at certain
periods during transformation and processed using con‑ventional methods. As has been documented by Inoki etal. (1971) , De Souza (1984) , and others, T. cruzi exhibits

tigotes, seemed to decrease in the course of transforma‑tion to assume the rod shape of the amastigote kineto‑
plast. Furthermore, in the event of this transformation

process, protein was analyzed by SDS‑PAGE andWestern blot. The mouse anti‑trypomastigote antiser‑um reacted with a major protein with a calculated MWof 68 kD. This major protein was observed to begreatest in trypomastigotes, reduced in transient inter‑mediate forms, and absent in amastigotes. This protein,cycle. In agreement with them, we observed that the

however, was observed to be present in epimastigote
forms, too. In accordance with Saborio and his col‑leagues (1989), this trypomastigote‑specific protein

trypomastigote has a loose spacious kinetoplast wherein

appears to be the paraaxial or parafiagellar rod protein.

the component DNA fibrils are arranged irregularly.
This kinetoplast form advances in regular compaction

This was confirmed by IFA and IEM which localized theprotein along the flagellum and on the complex lattice
structure of the paraflagellar rod, respectively. Fromthese observations, the trypomastigote‑specific protein

various forms of the kinetoplast at every stage in its lifein the intermediate forms of the parasite and, eventu‑
ally, develops into a rod‑like highly coiled kinetoplast
typical of the amastigote. However, a persistent obser‑
vation was made on the existence of a kinetoplast form
wherein the DNA fibrils are arranged in parallel rows.

The number of rows, which is greatest in trypomas‑

that appeared to decrease during transformation toamastigote is the paraflagellar rod protein. These
results likewise suggest, as other authors have, theimmunogenic property of this protein.

62 GENE ENCODlNG CY.STElNE PROTElNASE FROM TRYPANOSOMA RANGELIYOSHIMASA KANEDA*, TOMOO TANAKA* AND MANAMI TANAKA'
Department of Infectious Diseases, Tokai University School of
Medicine and Institute of Basic Medical Sciences,

Tsukuba University'

DNA fragments are obtained by the polymerase

ogenic and non pathogenic trypanosomes. After two

chain reaction (PCR) on genomic DNA fromstep amplification by PCR, two different fragments, 475Tr)panosoma rangeli using the oligonucleotide primers

proteinase. As cysteine proteinases of trypanosomes

and 498 bps, were finally obtained. These fragments
were subcloned into plasmid vector for the subsequent
sequence analysis and blot hybridization. The fragment

have been reported to be responsible for the invasion ofof 498 bp length (Tr‑CP) contains eight conserved

the parasite to host cells, it is of great interest tocompare the genetic variation of the gene among path‑sentative eukaryotic cysteine proteinases. Overall

encoding the active site amino acids of cysteineamino acids in N‑ and C‑terminal section of the repre‑

90(470 Kb) . The Tr‑CP cross‑hybridized with T. cruzi
chromosomes about I Mb, although the intensity washomology after alignment of the Tr‑CP amino acids tothe cysteine proteinases from the other trypanosome
species were 63% to T.. cruzi and 73% to T. brucei
gambiense, respectively. The chromosome size patterns

much different. Northern blot analysis revealed that Tr‑
CP gene was specifically expressed in T. rangeli as 1.7

and the location of the gene were analysis by pulse‑field

Kb mRNA.

gradient gel electrophoresis. T. rangeli has 14 chromo‑
somes ranging from 350 Kb to 1.6 Mb, which were fewer
in numbers and smaller sizes compared with those from

These results may suggest that (1) the non‑path‑ogbnic Tr)panosoma spp. contain the conserved genecorresponding to the cysteine proteinase or closely

T. cruzi. The Tr‑CP gene hybridized with an equal

related enzymes, and that (2) there is more than one copy

intensity to chromosomal I (350 Kb) and chromosome 2of this gene each found on different chromosomes.

63 SEARCH FOR THE PROTEINS THAT HAVE HIGH AFFlNITY
TO HIV‑I NEF

MASAHIRO INOUEl, KIMITAKA SAGAWA2, YASUHIRO KOGA3 AND
TOSHIHIDE FUKUMA1
Department of Parasitology and Department of Immunology'
Kurume University School of Medicine and Department of Immunology,
Medical Institute of Bioregulation, Kyushu Universityi

Nef is one of the non‑structural genes encoded inviral pathogenesis in vivo , an attempt was carrird out tothe genom of human immunodeficiency virus (HIV).

identify the host proteins which binds to Nef. First, theThe protein product is associated with the cellular and

Nef or deletion mutant derived from HIV‑1 Bru strain

plasma membrane, however its functional properties

was fused to Schistosoma japonicum glutathione S‑trans‑

concerning viral replication and pathogenesis has beenferase (GST) gene, and the fusion proteins were

failed to demonstrate in tissue culture studies, since theproduced. Then the glutathione bound chimera proteins
were used to search for cellular proteins that could
interact specificially with Nef. Second, using thepurified 32P‑labeled GST‑Nef or deleted Nef fusion
protein, we performed the Far Western blot analysis ofhuman T or monocytoied cell lines. We identified sev‑

viral replication in vitro is variably affected by muta‑
tions in Nef, and dependent on the host cell line.

However, an experiment performed in vivo using
the simian immunodeficiency virus (SIV) revealed thatrhesus monkeys, infected with the viruses generated
from molecular clone which carries complete Nef, devel‑
oped simian AIDS, in contrast, none of monkeys infectedwith Nef deleted viruses did.

eral proteins which carried relatively high affinity to
Nef. Further characterization of those proteins will be
discussed.

To understand the mechanism which affects the

64 A MOLECULAR ANALYSIS OF THE V3 GENE OF HIV‑1 ISOLATED IN UGANDASATOSHI MITARAI*, KAZUNORI OISHI*, TUYOSHI NAGATAKE*,

KEIZO MATSUMOTO* AND MASASHI FUKAZAWA'
Department of Internal Medicine and Department of Preventive Medicine',
Institute of Tropical Medicine, Nagasaki University

The V3 Ioop in gpl20 is one of the main targets forcharacteristics as an epitope with only a single amino

neutralizing antibody, antibody dependent cellularacid residue substitute in the V3 Ioop. It reduces initialcytotoxicity and cyiotoxic T‑lymphocytes in the early

immunological responses against HIV infection. There‑

phase of the HIV infection. The third variable region offore, it is important to investigate the diversity of thethe env gene has much diversity and it changes theenv gene to make an effective multipotential vaccine

91

inducing good and broad immunological responses
against HIV. We are now proceeding a collaboration
study with Makerere University about the therapy ofopportunistic infection in AIDS patients. We collected
several serum samples at the capital of Uganda in 1991
and directly extracted viral RNA of･･6 strains from theamino acid sequence GPGRAFV at the apex of the V3
loop. They have some mismatches around the apex
region, but they almost resemble to the American Eur‑
opean type and are different from the old African typealready reported. We assume these strains may be
imported from the neiboring countries or a result of
immunological selection. All patients were sufferingfrom pulmonary tuberculosis, so it may also affect thepatient's serum employing Polymerase Chain Reaction(PCR) amplification method. The patients were one
male and 5 female, and the mean age was 29.7. The PCR
product was cloned into plasmid vector and sequenced.

selection. In order to know the reason of type varitaion,
we have to investigate more patients in several parts of

All of the strains obtained from the patients have same

Uganda.

65 A MECHANISM OF INHIBITION OF NATURAL KILLER CELL ACTIVITYLEADING TO AIDS OPPORTUNISTIC INFECTION
TATSUO KIYOHARA1' 5, SHUICHI IKEDA2, SHIGERU KATAMlNE3,

MICHIO NAKAMURAl, MASAO TOMONAGA2, SHIGEO HlN03, 4

TSUTOMU MIYAMOTO 3 AND HIDEYO ITAKURA5
Department of Biochemistry* and Department of Pathology',
Institute of Tropical Medicine, Department of Hematology' andDepartment of Bacteriology3, Nagasaki University School of
Medicine̲. and Department of Virology, Tottori University
School of Medicine'

Natural killer (NK) cell activity and lymphokine

AIDS patients. To know the mechanism of suppression

activated killer (LAK) cell activity (activated in vitroof NK cytotoxic activity, we first prepared synthetic 17

with IL‑2) of peripheral blood lymphocytes (PBLs)

mer peptides conserved in retroviruses. CKS17 peptide

were assayed from normal volunteers, AIDS

equivalent to pl5E of retroviral envelope protein

asymptomatic carriers (A.C.) or AIDS patients. Amongthem, only NK cell cytotoxic activity was inhibited
exclusively in AIDS patients. PBLS from A.C. showednormal NK activity and LAK activity was intact during
the entire course of this disease. The results showedthat the patients are still in A.C. state (no onset of

effectively inhibited NK activity and LAK activity ofopportunistic infection yet) even if the CD4+lymphocytes are zero in PBLS as long as the NK cell
activity was intact. And they suggested that the NK

PBLS from A.C. and normal volunteers. On the con‑trary, plasma from AIDS patients inhibited NK activity
but not LAK activity. These results are fit to be thecellular immunity of AIDS patients. This plasma did
not contain HIV RNA detected by reversed PCR assay.
In summarized, we want to stress the significance of
natural immunity to protect the onset of opportunistic

infection in AIDS patients and some mechanism ofcells as well as CD4+ T Iymphocytes seem to be respon‑

impairing NK cell cytotoxic activity in AIDS plasma

sible for the susceptibility of opportunistic infections inseems to be responsible for this.

92

66 TREATMENT OF OROPHARYNGEAL CANDIDIASIS AND CRYPTOCOCCAL

MENlNGITIDIS IN HUMAN IMMUNODEFICIENCY VIRUS (HIV) ‑SEROPOSITIVEPATIENTS IN UGANDAKAZUNORI OISHll, SATOSHI MITARA11, TSUYOSHI NAGATAKE1

KEIZO MATSUMOTOI AND ROY MUGERWA2
Department of Internal Medicine, Institute of Tropical Medicine,

Nagasaki University

and Department of Medicine, Faculty of

Medicine, Makerere University, Uganda

We are now developing a collaborative projectcal meningitis entered the trial. The diagnosis wastitled "Treatment of AIDS‑related infections in Ugan‑da". In this paper, we demonstrated ongoing data on thegiven by testing cryptococcal staining with India ink andstudies of treatment with amphotericin B syrup for

patients. Cryptococcal culture was also done. Threehuman immunodeficiency virus (HIV)‑seropositiveCr)ptococcus neoformans were isolated. All the patients
sho ved weight loss ( > 10% of BW) , fever ( > I month) ,patients with oropharyngeal candidiasis and treatment
with oral fluconazole for these patients with cryptococ‑
cal menigitis.

cryptococcal antigen in cerebrospinal fluid (CSF) fromand oral candidiasis. Four patients responded to thetreatment with fluconazole (200 mg or 400 mg per day)oropharyngeal candidiasis were invited to the trial. 96.8% ,for 8 weeks. In these cases, the maintenance therapy
with low dose fiuconazole (200 mg per week) is given

54.8% , and 64.5% of patients showed weight loss ( > 10%

for 4 months. No reversed effects were observed.

of BW) , fever ( > I month) and diarrhea ( > I month) .

However, 6 patients did not responded to the therapy
and died due to meningitis within a week after theThirty one patients ( mean age: 30.7 y.o.) with

Nine Candida albicans strains were isolated frompatients. Clinical responses to the drug were evaluatedaccording to the oral findings and clinical symptoms(swallowing pain) . The treatment with amphotericin B
syrup (1,200 mg per day) for two weeks provided anefficacy rate of 67.7%. No reverse effects were noted.

initiation of the therapy. The delay of diaguosis andtherapy for this disease appears to lead HIV‑ sero‑
positive patients to death.

In summary, these preliminary data suggest theicin B syrup for oropharyngeal candidiasis in HIV‑clinical usefulness of amphotericin B syrup for orophar‑yngeal candidiasis and oral fluconazole for cryptococcal
meningitis in HIV‑seropositive patients. These studies

seropositive patients.

requires further investigations.

These data suggest the clinical usefulness of amphoter‑

Ten patients (mean age: 31.9 y.o.) with cryptococ‑

MARCH1993

VOL．21NO．1

CONTENTS
E〔litorial

Itakura，H．
Present Situation

andFutureProspectsof

TropicalMedicineinDeveloped

Countries・・1−3

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