平成4年12月15日

第20巻第4号
内
総容説
グアテマラにおけるブユの病原体およびそのオンコセルカ症媒介ブユ種に与える影響（英文）・…・……………・……一…………・………一………・…一高岡
Phylogenetic

relationships

among

the

generaof宏行

251−259

Dirofilariinae

sandground，1921（Nematoda：Onchocercidae）

一・Baharudin Bin
原著
フィラリア感染好適宿主としてのスナネズミの基礎的検討
一犬フィラリア虫体粗抗原によって誘導されたIgE様抗体一（英文）・・七戸 和博，清水 眞澄，加藤 一良，田村月舘

Omar 261−270

直彦，271−281

説子，藤田紘一郎

ナイジェリア国ジョスに於ける細菌性下痢症について（英文）一Agatha高橋

Ani，高橋 基久，才田利幸，佐藤春夫，谷口 博一，283一獅

麿人

大阪空港検疫所におけるインド・ネパール長期旅行者下痢症患者からのランブル鞭毛虫

検出成績…木村 明生，峯川 好一，池田 長繁，下入佐賢治，291−297
楠井 善久，松本 泰和，中林 敏夫

症例報告
ハロファントリンにより治癒した輸入三日熱マラリアの1例
一淀縄
聡，狩野 繁之，斎藤

川合

覚，鈴木

達也，横山

雄次，29卜303

守

熱帯熱，三日熱マラリア混合重症感染の1例 一artemetherによる治療経験一
・・穂坂
茂，石川
章，細野孝郎，飯国
近藤 啓文，ノ」￥林
豊，中村
健，伊藤
大友 弘士，狩野 繁之，鈴木守（裏面に続く）日本熱帯医学会

弥生，305−312
洋一，

研究ノートHealth，social justice and the third

republic………一………FestusThe

integrationdelivaryofservices：atraditional

healesIgharosa

Agbonlahor313−323

into the main−stream of our health care

re−apraisa1

・FestusIgharosa

Agbonlahor

投稿規定………・・……・…………一……・………・・………・……一…………●………………

32卜332333

日本医学会だより…………一……・………・…・……・・………一……・…………一……・…… 334−335

日本熱帯医学会雑誌

発行所

第20巻

編集者

第4号

1992年12月15日 印刷

1992年12月15日 発行

日本熱帯医学会板

倉英吾

印刷所昭和堂印刷
諌早市長野町1007−2（⑰854）
費0957−22−6000

本雑誌の刊行にあたりその費用の一部を文部省科学研究費補助金（研究成果公開促進費）によった。

JP . J. T*'P. M*d. Hyg., v*1' 20, N*. 4, 1992, pp. 251‑259 251

Review

PATHOGENS OF BLACKFLIES IN GUATEMALA AND
THEIR INFLUENCE ON NATURAL POPULATIONS
OF THE THREE ONCHOCERCIASIS VECTORSHIROYUKI TAKAOKA
Received September 10 1992/Accepted October 12 1992

Abstract: Pathogens and parasites of larval and adult blackflies so far found in
Guatemala were reviewed in relation to their host ranges, infection rates, and significanceas regulatory factors on natural populations of the three onchocerciasis vectors.

INTRODUCTION
Diseases are often found in larval and adult populations of blackflies. Included as causal

agents are viruses, bacteria, fungi, protozoa and helminths. Mermithids belonging to the lastgroup are most commonly encountered in larval and adult blackflies from all zoogeographicalregions. Pathogens and parasites of blackflies hitherto recorded from many parts of theworld have already been reviewed (Jenkins, 1964; Strand et al., 1977; Laird et al.. 1980; Laceyand Undeen, 1987) .
Recently, special attention has been paid to research on biocontrol agents in relation to

the future integrated control against simuliid vectors of onchocerciasis. For instance, inAfrica, where WHO/UNOP/WB Onchocerciasis Control Programme is now under way,
many studies have been carried out, and mermithid, fungal and protozoan parasites werereported from Simulium damnosum s. 1., a West African onchocerciasis vector (Lewis, 1960;
Briggs, 1970; Ezenwa et al., 1974; Mondet et al., 1977a, b) . Isomermis lairdi, the mostcommon parasite of this vector, has been extensively investigated with regard to its potential

as a biocontrol agent (Mondet et al., 1977b), although more studies must be carried out on
its practical use. Before the Japan‑Guatemala Onchocerciasis Pilot Project was commenced
in 1976, there were a few sporadic reports of parasitism in larval and adult populations ofGuatemalan simuliid vectors of onchocerciasis (Strong et al.. 1934; Dalmat, 1955; Garms,
1975) .

During the project, mermithids, fungi and ciliates were observed in adults of Guatemalan

blackflies (Ito et al.. 1980; Ochoa, 1982; Takaoka, 1982). Furthermore, pathogens andparasites of larval blackflies were surveyed, and their significance as regulatory factors uponnatural larval populations of three onchocerciasis vectors (S. ochraceum. S. metallicum andS. callidum) were studied (Takaoka, 1980, 1981).
This paper chiefly reviews the results of these recent studies.

Division of Medical Zoology, Oita Medical University, Idaigaoka 1‑1, Hazama, Oita 879‑55, Japan

252

PATHOGENS AND PARASITES OF ADULT BLACKFLIESTo date, bacteria, fungi, protozoa, nematodes and trematode have been recorded fromadult blackflies (Lewis and Wright, 1962; Jenkins, 1964; Strand et al.. 1977; Laird et al.. 1980) .

However, information i,s for the most part restricted to onchocerciasis vectors or related
species. Parasites other than Onchocerca volvulus larvae are usually detected, while wild
females are dissected for O. volvulus larvae in both natural and experi,mental infection
studies. Thus, as already mentioned, fungi, protozoa and nematodes have been reported f,rom
adult S. damnosum s. l. in Africa. These parasite groups were also observed in adults ofGuatemalan blackflies (Table 1) .

Nematodes
Mermithids afe frequently found in adult blackflies, since some proportions of infectedblackfiy larvae can pupate and emerge, parasite (s) within them being carried over up to theadult stage. Several species of mermithids belonging to Isomermis. Gastromermis, andMesomermis have been reported from adults of S. damnosum s. l. in West Africa (Mondet etal., 1977a) . In Guatemala, mermithid larvae of adult blackfiies were recorded for the firsttime by Strong et al. (1934) and later by several authors. Five blackfiy species including

three vector species are known to harbour mermithid nematodes (see Table 1). However,infection rates in each host were very low (0.09‑3.85%). The identity of mermithids con‑cerned remains unknown.
Next to mermithids, Iarvae of an unknown filaria are recognized in adults of S.
metallicum and S. horacioi (Garms, 1975; Ito et al., 1980; Takaoka, 1982). The third‑stage
larva of this filarial species was well described by Garms (1975). It is readily distinguishedfrom that of O. volvulus by its length (0.92‑1.29 mm) and by the presence of three caudal
protuberances. Rates of infection by this unknown filaria were all at low level, with a single
exception of 29.4% for S. horacioi reported by Ito et al. (1980).

Apart from the above‑mentioned nematodes, there are one or more nematode parasites
in adults of Guatemalan blackflies. One of these nematodes was first recorded by De Le6n
(1963) and later by Garms (1975) from the Malpighian tubes. According to De Le6n andDuke (1966) , it measures 0.9‑1.1 mm in length, possesses a pointed tail, and can remain viable

in normal saline or serum for up to 35 days. However, its infection rates appear to be low.

Protozoa
Microsporidans are very rarely recorded in adult blackfiies (Shipitsina, 1963; Hunter andMoorhouse, 1976) , although they are frequently observed in larval blackflies. In Guatemala,Strong et al. (1934) reported microsporidan infections in 34 Simulium females, while dissect‑ing S. ochraceum. S. metallicum and S. callidum to search for O. volvulus larvae. However,no adult flies infected by this protozoan parasite have since been reported in Guatemala.
Tetrahymena‑like ciliates have been recorded from adult S. damnosum s. l. (Lewis, 1960,1965) and adult and larval S. ruficorne (Takaoka, unpublished data) in West Africa, andfrom S. tahahasii in Japan (Takaoka, unpublished data). In Guatemala, ciliates parasitizing
adult blackflies were recorded for the first time by Strong et al. (host species were, though,not mentioned‑1934); similar protozoan parasites were again observed in three vector
blackflies (Garms, 1975; Ochoa, 1982). Infection levels were, though, very low.

253

Table l Pathogens and parasites found in adults of Guatemalan blackflies

Pathogens and Host blackfly
speaes% infection (authors)

Mermithids S. och'raceum

0.09 (Garms, 1975), 0.12 (Ochoa, 1982)

parasites 'S. metallicum

4.1 (Garms, 1975), 2.14 (Ochoa, 1982), 1.2 (Takaoka, 1982)

S, callidum

3.85 (Ochoa, 1982)

S. gonzalezi

1.3 (Garms, 1975)

S. horacioi

0.3 (Takaoka, 1982)

Unknown filaria S. metallicum
S. horacioi

Other nematodes S, ochraceum

0.3 (Garms, 1975), 1.0 (Ito et al., 1980), 0.2 (Takaoka, 1982)
29.4 (Ito et al., 1980), 0.1 (Takaoka, 1982)

0.4 (Garms, 1975), 0.06 (Takaoka, 1982)

S. metallicum

0.1 (Garms, 1975)

S. callidum

0.2 (Garms, 1975)

Ciliates S. ochraceum

0.2 (Garms, 1975)

S. metaJlicum

0.2 (Garms, 1975), 0.16 (Ochoa, 1982)

S. callidum

0.4 (Garms, 1975)

Fungi S. ochraceum

1.6 (Garms, 1975), 0.6 and 2.8 (Ochoa, 1982), 0.06 (Takaoka, 1982)

S. metallicum

0.4, 0.5 and 1.2 (Garms, 1975)

S. callidum

0.6, 0.9 and 1.3 (Garms, 1975')

S. gonzalezi

3.5 (Garms, 1975)

S. horacioi

0.1 (Takaoka, 1982)

Fungi
Infections caused by Phycomycetes have been recorded in ovaries of S. damnosum s. l.
in Liberia (Briggs, 1970) and of three blackfiy species in Canada (Undeen and Nolan, 1977) .
Garms ( 1975) reported fungi developing in ovaries of S. ochraceum. S. metallicum. S. callidum
and S. gonzalezi, and thought these fu,ngi as Phycomycetes. According to Ochoa (1982) , these

fungi may be classified into four types depending upon the shape of the parasitic forms(probably fungal thalli) . Infections by these fungi were sporadic, with low rates (0.06‑3.5%) .

No other fungal infections are recognized in Guatemalan blackflies, although Coelomycidium(Rubtsov, 1969). Entomophthora (Lewis, 1965) and Coelomomyces sp. (Garnham and Lewis,1959) have been very rarely recorded elsewhere.

PATHOGENS AND PARASITES OF LARVAL BLACKFLIESThere are many reports on pathogens and parasites of larval blackflies from various
parts of the world. However, until recently, no information was available in Guatemala
except for a report by Dalmat (1955) who found microsporidans in undetermined Simulium
larvae. In an investigation within and outside of the onchocerciasis endemic zones, Takaoka(1980, 1981) reported mermithid, microsporidan, fungal and viral infections in larval popula‑tions of blackflies, as su, mmarized in Table 2. Here included are brief notes on each groupof pathogens and parasites reported by the above author.

254

Mermithids
Mermithids including at least flve species were found in 17 species of Guatemalan
blackflies. Among these, four were already described as new species by Poinar and Takaoka(1979, 1981) .

Isomermis benevolus Poinar and Takaoka was shown to be a common parasite of larval
S. metallicum and S. callidum, and infections of both blackfly species with this nematode ina certain stream occurred throughout the year (averaging 8.5% and 14.1% respectively) withthe higher rates during the early dry months, October to January, than in the remainder ofthe year. The worm burden was one or two in S. metallicum but varied from one to sevenin S. callidum. Laboratory observations showed that at an incubation temperature of 18'C,
this mermithid parasite moulted on the sixth day after emergence and copulated one week
later; and eggs oviposited were seen two weeks after copulation.

Mesomermis uatemalae Poinar and Takaoka was described from S. metallicum.
However, no further information is yet available.
Another Mesomermis species, though undescribed, was found parasitizing S. callidum instreams at Finca Nimay (Takaoka, 1981). The number of parasites per infected simuliid
larva averaged one, with a maximum of three. Laboratory rearings at 16'C revealed thatmoulting occurred at sixth to eighth days after emergence, copulation taking place five days
later.

Table 2 Host ranges of pathogens or parasites in Guatemalan blackfly larvae
Host species

Mermi‑ T. bra.

thids

Gigantodax wrighti+*

Cnephia aguirrei+

C, pacheco ‑ Iunai+b+

T, var.

T. fi b.

T.sp‑l T,sp‑2

+

+

+

+
+

P. deb.

P. mul. P. sp‑ 1 P.sp‑2

Py, spC, sp

IV CPV++

Simulium aureum
S. rubicundulum
S. paynei
S. earlei

S, pulverulentum

+
+
+
+

S, nigricornis

S. samboni

+
+
+
+
+

S. callidum+'

S. tricornis

S, veracruzanum

S. haematopotum
S. downsi+*

S, pua i'+

S. horacioi++

S, patziciaensef

+
+

+
+
+

+

+
+

+

+

+

+
+

+

+

S, ochraceum
S, metallicum

+

+
+

+

+

+

+

+

+
+
+

+
+
+
+
+
+

+

+

+

+

+
+
+
+
+

a, Gastromermis cloacachilus; b, Isomermis vulvachila; c, I. benevolus and Mesomermis sp.;d, I. benevolus and M. guatemalae; e, misidentified as S. jobbinsi in the previous paper (Takaoka, 1981);

f, previously reported as S. sp‑2 (Takaoka, 1981).

+

255

Gastromermis cloacachilus and I. vulvachila, also described by Poinar and Takaoka, are,each, a parasite of Gigantodax wrighti and Cnephia pacheco‑lunai from upland streams (ca.
2,800‑3,000 m above sea leveD of the non‑endemic area.
It is intriguing that no mermithid parasites were recovered in larval S. ochraceum,
although mermithid infections were observed in adults of this species.

Microsporidans
Microsporidan protozoa are widespread in larval blackfiies around the world whereversearched for. In Guatemala, 10 microsporidan species ( Thelohania, 5 spp., Pleistophora. 4 spp.,

and f /rotheca (?) , I sp.) were reported from larvae of 15 blackfiy species (Table 2). The

genus Thelohania includes two undescribed species as well as three known and cosmopolitan
ones ( T. bracteata. T. varians and T. fibrata). All of these Thelohania species have a wide
host range except for T. fibrata which was recognized in two blackfly species. On the other
hand, two undescribed Pleistophora are highly host specific, P. sp‑1 and P. sp‑2 parasitizing
S. callidum and S. horacioi respectively; whereas, as in other parts of the world, P. multlspora

is a common parasite, utilizing eight blackfiy species as a host.

Three microsporidans (T. bracteata. T. sp‑2 and P. multispora) were occasionally foundin larval S. ochraceum. On the other hand, 11 the five Thelohania species and P. multispora
were encountered in S. metallicum, and T. varians. P. multispora. P. sp‑1 and P. debaisieuxi
in S. callidum.

Fungi
The fungal infections found in nine Guatemalan blackfly species including S. ochraceumand S. meiallicum were caused by Coelomycidium sp. (probably C. simulii, a common parasiteof larval blackflies around the world). This fungus is widely distributed within and outside
the onchocerciasis areas. However, its infection rates in two vector species as well as in otherblackfly species were very low.

Viruses
There have been very few reports of viral infections among larval blackflies. Until now,

three groups of baculoviruses have been reported: iridescent viruses (IVs) from Czechoslova‑

kia (Weiser, 1968) and England (Batson et al., 1976), cytoplasmic polyhedrosis viruses(CPVs) from Canada (Bailey et al., 1975), Czechoslovakia (Weiser, 1978) and USA(Federici and Lacey, 1976), and densonucleosis viruses (DVs) from USA (Federici, 1976).
In Guatemala, infections caused by IVs were recognized in four blackfly species including

S. metallicum and S. callidum from two streams in the onchocerciasis‑endemic areas(Takaoka, 1980, 1981); and the CPV infection was also found in larval S. aureum from two

upland streams (Takaoka, 1980).

INFLUENCES OF PATHOGENS ON NATURAL LARVAL POPULATIONS OF THREEONCHOCERCIASIS VECTORS
Influences of pathogens and parasites of various categories on natural larval populationsof three vectors have been reported by Takaoka (1980, 1981) .
Table 3 shows the incidence of mermithids, microsporidans, fungi and viruses in three256

vector species. Simulium ochraceum exhibited only sporadic parasitaemia by comparison
with S. metallicum and S. callidum. That is, infections due to pathogens of any kinds were
found only in six of 44 streams where S. ochraceum were collected. Furthermore, this species

is unique in lacking mermithid and viral infections. On the other hand, Iarvae of S.
metallicum and S. callidum were most frequently found to harbour mermithids and mi‑
crosporidans, fungal and viral infections being, though, sporadic.
Infection levels of these pathogens in the infected larval populations of three vector

species are shown in Table 4. Simulium ochraceum showed the low infection rate (2.7%) bycomparison with S. metallicum (13.9%) and S. callidum (7.9%) . Average infection rates withmermithids in the larval populations of S. metallicum and S. callidum were 8.9% and 4.9%,
respectively. However, infections with microsporidans and Coelomycidium were all at low
levels.

In view of the various habitats utilized by three vector species, monthly or bi‑weekly
observations were made in different types of breeding streams in the onchocerciasis‑endemicareas. The results showed that S. ochraceum never harboured mermithids, even in mid orlower parts of perennial streams where the other two secondary vectors were heavily
parasitized by mermithids. It was also shown that mermithid infections in larval populationsof S. metallicum and S. callidum were significantly higher in mid or lower parts of permanent

streams than in upper parts of permanent streams or in temporary ones. Moreover, seasonalchange in mermithid infection rates in perennial streams showed a distinct pattern, withincreased infection rates during the dry season (November to ApriD and lowered rates
Table 3 Prevalence of pathogens in larval populations of three blackhy vectors of onchocer‑

ciasis in Guatemala

Number (%) streams where:
Larvae were infected with:

Host species

Host species collected Any parasites Mermithids Microsporida Coelomycidium lridescent virus
S, ochraceum

44

S, metallicum52

S. callidum

33

O (‑)5 (11.4)
6 (13.6)

28 (53.9)
36 (69.2)
24 (46.2)
12 (36.4)
21 (63.6) 12 (36.4)

3 (6.8)O (‑)

2 (3.9)1 (1,9)O (‑)

2 (6.1)

Table 4 Levels of infection with pathogens in infected larval populations of three blackfly

vectors of onchocerciasis in Guatemala
Infection rate (olo)Host species

Any parasites Mermithids Microsporida Coelomycidium lridescent virus

S. ochraceum

2 . 7'(O . 3‑7 , l) b

S. metallicum
S, callidum

a, median; b, range

O

(‑)

3.6

2.2

(2 . 7‑7 . 1)

(O . 3‑2 . 7)O(‑)

13 . 9

8.9

3.0

l.3

0.5

( I . 3‑75 . O)

( I . 5‑75 . O)

(O . 4‑26 . O)

(O . 1‑2 . 5)

(O . 5)

7.9

4.9

1.7

(O . 3‑50 . 5)

(O . 7‑50 , O)

(O . 3‑50 . O)

O

(‑)

7.6
(5 . 1‑10 . 1)

257

throughout the remainder of the year. The level of microsporidan infections of S. ochraceum
also varied in relation to the different types of preimaginal habitats. This species exhibitedvery low infection rates in permanent streams but was free from microsporidan infection in
temporary streams. In contrast, S. metallicum and S. callidum were equally parasitized in all
types of strearns at low infection levels. Fungal infections due to Coelomycidium (at a very
low leveD were found only in perennial streams.
Overall, it is summarized that mermithids play the chief role in suppressing natural larval

populations of S. metallicum and S. callidum in the mid or lower parts of perennial streams,

especially during the dry season; they hardly do so, however, in upper parts of permanent
streams or in temporary ones. Other groups of pathogens are considered to be of negligible
importance ' as natural population regulatory factors for the three vector species in all typesof breeding streams.

CONCLUSION
Recent studies indicate that various kinds of pathogens and parasites including several

new taxa are present in larval and adult populations of Guatemalan blackflies. As in otherparts of the world, Coelomycidium fungi, microsporidans and mermithids are frequently
observed in larval blackflies. However, infections by these pathogens are generally at low
level.

It has been shown that influence of these pathogens on natural larval populations of threeonchocerciasis vectors varies significantly. For instance, S. ochraceum, the principal vector,

never harboured mermithid nematodes, while S. meiallicum and S. callidum (the secondary
vectors) were frequently parasitized by this parasite group.

Four mermithid nematodes have been newly described and their life history have been
preliminarily studied in the laboratory. However, the potential of these mermithid parasites
for simuliid control needs further study.

Finally, in view of exotic biocontrol agents against simuliid vectors, it should be
mentioned that due to its pathogenicity, potential for mass‑production and safety for man
and nontarget organisms, Bacillus thuringiensis var. israelensis de Barjac, a pathogen of
mosquitoes, is now recognized as one of the most promising biological agents for the controlof larvae of blackflies as well as mosquitoes (Burges et al., 1981) . In fact, it has been provento be highly pathogenic to larval S. ochraceum, yielding high mortality under both laboratory
and field conditions (Undeen et al., 1980).

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Castillo, Eds) Bull. Wld Hlth Org., 58 (Suppl.), 1‑197

18) Lewis, D.J. (1960): Observations on Simulium damnosum in the southern Cameroons andLiberia, Ann. Trop. Med. Parasitol., 54, 208‑223

19) Lewis, D.J. (1965): Features of the Simulium damnosum population of the Kumba area inWest Cameroon, Ann. Trop. Med. Parasitol., 59, 365‑374
20) Lewis, D.J. and Wright, C.A. (1962): A trematode parasite of Simulium, Nature, 193, 1311‑1312
21) Mondet, B., Poinar, G.O., Jr. and Bernadou, J. (1977a): tude du parasitisme des simulies(Diptera: Simuliidae) par des Mermithidae (Nematoda) en Afrique de l'Ouest. II. Description
de deux nouvelles especes de Gastromermis. Can. J. Zool., 55, 1275‑1283
22) Mondet, B., Poinar, G.O., Jr. and Bernadou, J. (1977b): tude du parasitisme des simulies(Diptera: Simuliidae) par des Mermithidae (Nematoda) en Afrique de l'Ouest. IV. Description
de Isomermis lairdi n. sp., parasite de Simulium damnosum. C, an. J. Zool., 55, 2011‑201723) Ochoa A., J.O. (1982): Studies on the anthropophilic blackfiy species in Guatemala, withspecial reference to the transmission of onchocerciasis in the southeastern endemic area, Jpn.
J. Sanit. Zool., 33, 129‑138

25924) Poinar, G.O., Jr. and Takaoka, H. (1979): Isomermis benevolus sp. n. (Mermithidae:
Nematode) a parasite of Simulium metallicum (Diptera: Simuliidae) in Guatemala, Jpn. J.
Sanit. Zool., 30, 305‑307

25) Poinar, G.O., Jr. and Takaoka, H. (1981): Three new mermithids (Nematoda) from
Guatemalan black flies (Diptera: Simuliidae), J. Systern. Parasitol., 3, 13‑1926) Rubtsov, I.A. (1969): Variability and relationships of coelomycidians with the host, Zh.
Obshch. Biol., 30, 165‑173
27) Shipitsina, N.K. (1963): Parasitic infection of simuliids (Diptera) and its effect on ovarianfunction, Zool. Zh., 42, 291‑294

28) Strand, M.A., Bailey, C.H. and Laird, M. (1977): Pathogens of Simuliidae (Blackflies) . In
Pathogens of medically important arthropods, pp. 213‑255 (D.W. Roberts and M.A. Stand,eds.). Bull. Wld Hlth Org., 55, (Suppl. l), 1‑419
29) Strong, R.P., Sandground, J.H., Bequaert, J.C. and Mufioz Ochoa, M. (1934): Onchocerciasis
with special reference to the Central American form of the disease, Contr. Harv. Inst. Trop.
Biol. Med., 6, 1‑23430) Takaoka, H. (1980): Pathogens of blackfly larvae in Guatemala and their influence on natural
populations of three species of onchocerciasis vectors, Am. J. Trop. Med. Hyg., 29, 467‑472
31) Takaoka, H. (1981): Further studies of pathogens of blackfly larvae in Guatemala and theirinfluence on natural populations of three species of onchocerciasis vectors, In Biocontrol of
medical and veterinary pests. pp. 78‑104 (M. Laird, ed.), New York, Praeger32) Takaoka, H. (1982): Observations on the bionomics of larval and man‑biting female popula‑tions of Simulium horacioi, a new potential vector of Onchocerca volvulus in Guatemala, Jpn.
J. Trop. Med. Hyg., lO, 49‑62
33) Undeen, A.H. and Nolan, R.A. (1977): Ovarian infection and fungal spore oviposition in theblackfly Prosimulium mixtum. J. Invert. Pathol., 30, 97‑98
34) Undeen, A.H., Takaoka, H. and Hansen, K. (1980): The evaluation of Bacillus thuringiensis

var. israelensis de Bajac as a larvicide for use against Simulium ochraceum, the Central
American vector of onchocerciasis, Mosquito News, 41, 37‑4035) Weiser, J. (1968): Iridescent virus from the blackfly Simulium ornatum Meigen in Czechos‑
lovakia, J. Invert. Pathol., 12, 36‑3936) Weiser, J. (1978) : A new host Simulium argyreatum for the cytoplasmic polyhedrosis virus ofblackflies in Czechoslovakia, Folia Parasitol., 25, 361‑365

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Jpn. J. Trop. Med. Hyg., Vol. 20, No. 4, 1992, pp. 261 270

261

Review

PHYLOGENETIC RELATIONSHIPS AMONG
THE GENERA OF DIROFILARIINAE SANDGROUND,
1921 (NEMATODA= ONCHOCERCIDAE)BAHARUDIN BIN OMAR
Received February 27 1991/Accepted August 2 1992

Abstract: Phylogenetic relationships among the genera of the filarioid wotm of
subfamily Dirofilariinae were analysed based on cladistic. Fourteen characters among
Macacanema, Edesonfilaria, Dirofilaria. Loaina,' Pelecitus. Foleyella, Loa and I ostrichodera

were compared resulting in a consensus phylogenetic tree. The last six genera form agroup with at least one synapomorphy, and Foleyella. Loaina and Pelecitus are the mostderived among the subfarnily. Edesonfilaria and Macacanema most probably belong to a
subfamily other than Dirofilariinae.

INTRODUCTION
The aim of modern systematics is not only to provide easy and accurate recognition of
species but also an elucidation of their evolutionary history.

Previous classifications of Onchocercidae were presented by Yorke and Maplestone(1926), Wehr (1935), Lopez‑Neyra (1956). Chabaud and Choquet (1953) and Anderson andBain (1976). The currently accepted relationships within the family were developed by
Chabaud and Anderson (1959) and later expanded by Anderson and Bain (1976) .
The Onchocercidae may be a monophyletic group in the order Spirurida, as can be
implied from the works of Chabaud and Bain (1976) . They are medium to small sizednematodes with reduced buccal capsules, have arthropods as intermediate hosts, and occur inthe connective tissues and heart of large blood vessels of terresterial vertebrates.
In systematics, considerable interest has been directed towards the concepts and methodsof phylogenetic construction by numerical methods. One of the concepts and techniques forreconstructing the branching aspect of phylogeny have come to be known as cladistics or
phylogenetic systematics (Hennig, 1965) . Phylogenetic systematics attempt to recover the
relationships among groups of organisms and produce classifications that reflect their
geneological relationships (Wiley, 1981) .

This study attempts to contruct hypotheses of relationships among the genera of
Dirofilariinae. Morphological informations on the genera Macacanema. Edesonfilaria. Bostri‑chodera. Loa. Foleyella. Loaina. Pelecitus, and Dirofilaria are available in substantial detail.

The literature on Dirofilariaeformia and Skrjabinodera is too scanty to be of use in the

Department of Parasitology and Medical Ehtomology, F culty of Medicine, Universiti Kebangsaan

Malaysia, P.O.Box 12418, 50778 Kuala Lumpur, Malaysia

262

analysis. As such, these last two genera are not included in the analysis of Dirofilariinae.

MATERIALS AND METHODS
The choice of genera in the subfamily is based on the works of Anderson and Bain
(1976) . Skrjabinodera and Dirofilariaeformea are excluded for lack of information and future

works might clarify the true status of these two genera in the systematics of Dirofilariinae.

The characters of the following 8 genera were evaluated:

Macacanema
2

Edesonfilaria

3. Dirofi laria

4. Loaina
5. Pel ecitus
6. Fo leye lla
7. Loa
8. Bostrichod era

Method of Phylogenetic Analysis
In this study, the writer has employed version 2.4 of PAUP (Phylogenetic Analysis Using
Parsirnony) , a computer program developed by Dr. David L. Swafford of lllinois Natural

History Survey, Illinois. The parsimony program chosen for this package is Wagner
Parsimony. The logic of using Wagner Parsimony is well documented (See Maddison et al..
1984; and others) . It should be noted that parsimony has nothing to do with evolution but ismore of a matter of explaining data as simply as possible. Wagner parsimony allows
character state changes from plesiomorphic (ancestral) to the apomorphic (derived states) ,equally allows reversals to the plesiomorphic states, and attemps to construct a cladogramwith the manimum total number of state transitions. One of the simplest parsimony models
is that the preferred tree is the one of minimal length in Manhattan matrix with no a priori
restrictions on the nature of permissible character state changes (Swafford, 1985) .

In order to strengthen the outgroup process of character state transformation,
Skrjabinofilaria. Acanthocheilonema. Oswaldofilan l and Chablfilaria were used as outgroup
genera based on the works of Chabaud and Bain (1976) , Bain (1981) , and Bain and Chabaud(1986). Maddison et al. (1984) emphasized the importance of using more than one outgrouptaxon simultaneously in order to determine correctly both the position and the direction ofcharacter state changes in the ingroup phylogeny. In this analysis the ingroup taxon are
represented by the 8 genera being mentioned.
Explanation for Choice of Characters in Preliminary Analysis
Fourteen characters were used for the analysis. Primitive characters were listed as 'O'
and the derived characters as '1', '2', '3' and so on. The ordinal value of '9' was considered
as a missing value due to lack of description or if more than one state (i.e, multistates) was

found for that particular character among the members of the genus. The characters
together with their character states and polarities are described in Table 1.

263

Table l Characters and their discrete states used in analysis
1 . Shape of male tail0=coiled about 2‑4 turns
l =coiled 0.5‑1.5 turns

Polarity: O ‑ 1
2 . Length of tail0=10ng (length more than two and a half times width at anus)
1 = short (length less than two and a half times width at anus)

Polarity: O ‑ 1

3 . Shape of preanal papillae

0=small and non pedunculated
1 = pedunculated

2=bulbous without stalk
Polarity: O ‑ I ‑ 2

4 Caudal alaeOabsent1 = present but incospicuous

2=highly conspicuous and without hyaline inclusions
Polarity: O ‑ I ‑ 2
5 . Arrangement of preanal papillae
0=grouped near to each other but not in contact
1 = grouped very closely at terminal end and in contact with each other

2 =widely spaced from each other
Polarity: 2 ‑ O ‑ 1
6 . Dissimilarity of paired spicules' shape

O =highly dissimilar
1 = subequal

Polarity: O ‑ 1
7 . Spicular ratio
O = 2‑4

1 =1ess than 1.9

2 =more than 4
Polarity: 2 ‑ O ‑ 1
8 . Shape of left spicule0=1amina highly filamentous and almost two times longer than calomus
1=1amina filamentous or non‑filamentous and is equal or slightly longer than calomus

2 =1amina highly sclerotized, non filamentous and very much shorter than calomus

3=highly tubular and long, and without any apparent division into calomus and lamina
Polarity: 2 ‑ O ‑l
3

9 . Shape of right spicule

0=not divided into calomus and lamina but has blunt end
1=clearly divided into delicate calomus and sclerotised lamina with pointed end
2=not clearly divided but with extra internal sclerotization; Iightly sclerotized

Polarity: 2 ‑ O ‑ 1

264

Table I (continued)
10. Esophago‑intestinal junction

0=with valve
1 = without valve

Polarity: O ‑ 1

11. Division of esophagus
O = esophagus with muscular and glandular parts; and the glandular portion wider than the muscularparts, 1=esophagus without division into muscular and glandular portions
2=esophagus with muscular part and glandular part but glandular portion nucleated
Polarity: 2 ‑ O ‑ 1
12. Position of vulva

0= at region of muscular esophagus
1 =at region of glandular esophagus or post‑esophageal
Polarity: O ‑ l

1 . Shape of ovejector

0=highly bulbous and heavily muscularised
l =non‑bulbous and lightly muscularised
Polarity: O ‑ 1
14. Microfilaria
O = sheathed

1 = unsheathed

Polarity: O ‑ lCharacter l. Shape of male tailThe male tail in most members of family Onchocercidae is coiled two to three turns.
This character is found in the four genera of Onchocercinae used as distant outgroups and isalso present in some members of study group Dirofilariinae. This character is regarded as a
symplesiomorphy. Foleyella, Loa, Loaina and Pelecitus have tails that are coiled 0.5 to 1.5
turns and thereby noted as a synapomorphy.
Character 2. Length of male tailThe tail is considered being long if its length (distance between anus and posterior endof body) is more than two and a half times that of the width at anus. This character isconsidered as, primitive, (indicated as 'O'). Acanthocheilonema, Skrjabinofilaria.
Oswaldofilaria and Chablfilaria and in fact majority of Onchocercidae, have this
symplesiomorphy. A short tail is found among members of Dirofilaria. Foleyella. Pelecitus.
Loaina. Loa, Edesonfilaria and Macacanema and is a synapomorphy for these genera. Anothersubfamily in the Onchocercidae which consistently has a short tail is the Lemdaninae.

Character 3. Shape of preanal papillae
In the majority of outgroups (Acanthocheilonema and Oswaldofilaria and Chablfilaria) the
preanal papillae are small and not pedunculated. In the subfamily Dirofilariinae, the genera
Dirofilaria. Foleyella. Loa. Pelecitus, Loaina and Bostrichodera have highly pedunculated
preanal papillae. Having pedunculated papillae is proposed as a synapomorphic character.

z65

Character 4. Caudal alae
The outgroups do not have this morphological feature except for Skrjabinofilaria which
has a single caudal ala. Absence of caudal alae is considered a primitive state; however, nosimilar state could be found among the Dirofilariinae. It is postulated that having caudal alae

is a synapomorphy for all members of Dirofilariinae. In order to resolve the relationships
among the mernbers of this subfamily, it is suggested that having small or not highly marked
caudal alae as can be found in Macacanema and Edesonfilaria as the most recently evolved
feature of caudal alae.

Character 5. Arrangement of papillae
The arrangement of the papillae can at times be variable even among the worms of same
species. However, there is a consistency among the genera of the overall pattern of papillae
groupings. In Acanthocheilonema. Oswaldofilarla. Skrfabinofilan 1 and Chablfilaria, the papil‑
lae are grouped near each other but not to the extent that they are in contact with each other.

This feature is considered as primitive.

Character 6. Dissimilarity of paried spicules' shape
In outgroup genera and in a majority of Onchocercidae, the left and right spicules arehighly dissimilar in shape. This feature is suggested as a plesiomorphic character.

Character 7. Spicular ratio
A majority of the spicules of the members of the outgroup genera have the ratio of left
to right spicules ranging between two and four. PossessiQn of this feature is considered asa syrnplesiomorphy. A ratio of higher than four or less than two is considered to be a derived
character.

Character 8. Shape of left spicule
For Acanthocheilonema, Skrjabinofilaria and Oswaldofilaria, the left spicule is divided intoa calomus and a lamina. Both portions are usually well‑sclerotized. The lamina is usually
between I and 2 times the length of the calomus and is not filamentous. A Ieft spicule fitting
this description is considered as primitive and other features are thereby treated as derived.

Character 9. Shape of right spicule
A right spicule that is not divided into a calomus and lamina, Iacks an internal line ofsclerotizations, and has a slightly or very blunt end, has the features common to the out‑groups and is thereby considered to be primitive.

Character lO. Esophago‑intestinal junction
A valve between the esophagus and the intestine is common among the species of theoutgroup and the genera in the family Onchocercidae. Absence of this feature is considered
as derived.

Character 11. Division of the esophagus
All members of the outgroup have the esophagus divided into muscular and glandular
portions, with the latter being much wider and longer than the' former. Absence of this266

division is considered as an apomorphic feature.

Character 12. Position of vulva
The position of the vulva is variable among the species of the outgroup. The vulva in
Oswaldofilaria is usually equatorial, while in Skrjabinofilaria it is commonly at the level of themuscular portion or the anterior part of the glandular portion of the esophagus. In contrast,in Acanthocheilonema the vulva is located near the end of the glandular portion of esophagus

or is post‑esophageal. An ontogenic criterion has to be invoked in this matter. In filarial

wdrms whose development have been elucidated, it has been shown that the vulva in theimtnature female worm is usually situated in the anterior or middle region of the esophagus.
There is a tendency for the vulva to be positioned more posteriorly in relation to its former
position as the worm matures. It is suggested that the position of the vulva in anterior regionof esophagus (muscular portion) is a primitive feature.

Character 13. Shape of ovejector
All the outgroups and some of the ingroups have bulbous and highly muscular ovejectors.
Possession of this' feature is proposed as a symlesiornorphy.
Edesalf llarLa". ¥F ,
D acutl I,SCUla

DrEpels
D. ursiD suWeT11 ta

D IUtTEe
D I cradd!IDs

D polol nsis
Bostric,njerl

D. CJ,!1,:riWriD, corynodes

D strlata
D iJmlitls
D. i!agnllallJ5tul]

D tertJis[
P*]*l *l i=

F*1 *y"I l*

Figure 1 Consensus tree of phylogenetic relationships

among genera of Dirofilariiae.

267

Character 14. Microfilaria
Having a sheathed microfilaria is considered as primitive since the sheath is an embry.
onic feature. La̲ck of a sheath is thereby a derived feature. Bain et al. (1982) also suggestthat the sheathed microfilariae is a primitive feature.
Cladistic Analysis

Each character was transformed into a multistate character using ordinal values (Tablel). In this analysis characters 7, 8, 9 and 11 were entered as unordered. The 14 charactersand 2,1 taxa was run 10 times, with a differing order of taxa each time, using David Swafford's

PAUP Wagner Parsimony program.
Fifty trees were obtained by default for the maximum of trees that can be obtained fromPAUP output. To compare the 50 trees and define areas of congruence, the CONTREE
program version 1/3/86 available in PAUP was used.

RESULTS
The default maximum of 50 trees obtained had 26 steps and a consistency index of 0.808.

The consensus tree is shown in Figure l.
The phylogenetic tree shows that the subfamily shared the characters of short tails,
presence of caudal alae, unsheathed microfilariae, and left spicule highly tubular, Iong andwithout any apparent division into calomus and lamina. Edesonfilaria and Macacanema havesynapomorphies of havihg esophago‑intestinal junction withotit valve; esophagus divided into
muscular and, glandular portions, with the later being mucleated and a spicular ratio of morethan 4. Edesonfilaria, meanwhile, is separated from Macacanema by having the left spicule
highly tubular angl long with no apparent division into calomus and lamina. Macacanema has
the autapomorphic features of right spicule clearly divided into delicate calomus and scler‑otised lamina with the later having pointed end; and the left spicule with the features oflamina highly sclerotised, non filamentous and very much shorter than calomus.
Bostrichodera. Dirofilaria, Foleyella. Pelecitus. Loaina and Loa are separated from

Edesonfilaria and Macacanema by the synapomorphies of having pedunculated preanal
papillae; Iamina of left spicule filamentous and almost two times longer than calomus; highly

conspicuous caudal alae; and esophagal valve at region of glandular esophagus or post‑esophageal.
Dirofilaria cancrivori, D. corynodes. D. striata, D. immitis, D. magrdlarvatum. D. tenuis,Loa, Pelecitus, Loaina and Foleyella are separated from Edesonfilaria. Macacanema. Bostri‑chodera. D. acutiuscula. D. repens. D. ursi D. subdermata, and D. panamensis by having theesophagus not conspicuously divided into muscular and glandular portions or the presence ofboth divided and undivided esophagus in the species of some genera (as in Pelecitus andFoleyella represented by ordinal value 9 in the data matrix) .

Loa. Pelecitus. Loaina and Foleyella have two synapomorphies separating them from theother genera of Dirofilariinae whereby male tail coiled 0.5‑1.5 turns, and non‑bulbous andlightly musculariased ovejector. Pelecitus. Loaina and Foleyella shared the apomorphic
character of the right spicule lightly sclerotised, clearly divided into calomus and lamina, butwith internal sclerotization.

Loaina has the autapormphies of snbequal spicules and anal papillae grouped very

268

closely and in contact with each other at the terminal end.
Two reversals occured among the Dirofilariinae: I ) Loa. Pelecitus, Loaina and Foleyellahaving sheathed microfilaria 2 ) D. striata, D. immitis. D. magnilarvatum. D. tenuis, Loa,
Pelecitus, Loaina and Foleyella having left spicule's lamina non‑filamentous and are one to

two times the length of calomus.

DISCUSSION
All the generb in Dirofilariinae being examined were found by the analysis to share 4
apomorphic characters: tail being short, presence of caudal alae, unsheathed microfilariae,
and left spicule being highly tubular, Iong and without any different division into calomus andlamina. Examination of all 50 trees revealed the presence of the last character. This feature
is one of 3 states used as an 'unordered' in the analysis (character 8) . It appears again as an

autapomorphy for Edesonfilaria. The three other characters just mentioned are also not
unique in Dirofilariinae since they are present in some genera in Onchocercinae and Lem‑daninae. This finding is not surprising since the choice of characters for Dirofilariinae in the

preliminary analysis depended heavily on descriptions of those worms from literature.
Macacanema and Edesonfilaria together with the above genera do not fulfill the require‑ments for being altogether monophyletic. Bartlett (1987) suggested that Edesonfilaria andMacacanema could possibly belong to a subfamily other than Dirofilariinae, i.e., Lemdaninae.
This proposal appears valid based on the results of the present study. The characters thatgrouped them together were most probably homoplasies within Filarioidea. On the other
hand, Dirofilaria. Bostrichodera. Loa. Foleyella. Pelecitus and Loaina form a group with atleast one synapomorphy.
Loa. Pelecitus. Loaina and Foleyella are more dirived phylogenetically than Dirofilaria.

They are characterised by the derived characters of the male tail coiled less than 2 turns,
ovejector non‑bulbous and lightly muscularised and a reversal character of the microfilariae(i.e., sheathed microfilariae) . Among these four genera, Loa is more primitive due to theabsence of internal sclerotization in the right spicule.

Pelecitus. Loaina and Foleyella share the same nested grouping among the Dirofilariinae.

Bartlett (1983) postulated a close relationships between Loaina umformis and Pelecitus
scapiceps. The results of this phylogenetic analysis show that these two worms share sistergroup relationships.

Consensus cladogram of the subfamily (Figure 1) proposes that Foleyella. Loaina and

Pelecitus are members of a monophyletic group and . are the most derived among
Dirofilariinae. The genera of Dirofilariinae were revealed by the cladogram as polyphyletic,and Edesonfilaria and Macacanena most probably belong to a different subfamily. Further
studies are needed to examine all the genera in the subfamily, and find additional homologous

characters to elucidate their phylogeny.
Decision on primitiveness of a particular organism can be complicated and difflcult. The

results of cladistic analysis rely heavily on choice of characters and their polarities. The

more information available on a particular group of organisms especially that pertaining totheir evolution, the less difficult is the task of postulating the directionality of evolution ofcharacters. It must be recognised that information regarding each genus is only as good as
the description provided by the investigators. Rodman et al. (1984) stated that the value of269

an explicit, character supported phylogenetic tree is that it provides resolved geneologies fortesting with new data and also new context for rethinking character homologies, particularly

where they are co;rtroversial. Future studies might provide new data that are most probably
improve the cladogram obtained in this study.

This study is among the first attempts to discover phylogenetic relationships among ataxon of Filarioidea based on the concepts of cladistics on phylogenetic systematics. The
techniques utilized are procedurally defined and repeatable, and as such open to criticism andtesting.

ACKNOWLEDGEMENTS
I am very grateful to Drs Thomas C. Orihel and J.H. Esslinger of the Tulane University
at New Orleans for their advices and constant guides while this tudy is carried out. I am
especially indebted to Dr. T.C. Orihel for allowing me to use his collection materials and forborrowing the'type specimens from Institute of Parasitology, Bethesda. Maryland, U.S.A.
The Universiti Kebangsaan Malaysia provided scholarship support for the duration of study.

REFERENCESl ) Anderson, R.C. and Bain, O. (1976) : No. 3 keys to the genera of the Order Spirurida, part 3.

Diplotrianoidea, Aproctoidea and Filarioidea. In: CIH Keys to the Nematode Parasites ofVertebrates, Commonwealth Agriculture Bureaux, England2 ) Bain, O. (1981): Onchocerca: hypotheses sur son evolution et cle dichotomique des especes,
Annales de Parasitologie Humaine et Comparee, 56, 503‑526
3 ) Bain, O. and Chabaud, A.G. (1986): Atlas of infective larvae of filarial parasites, Trop. Med.
Parasitol., 37, 301‑340

4 ) Bain. O., Baker, M. and Chabaud A.G. (1982): Nouvelles donnes sur la lignee Dipetalonema(Filarioidea, Nematoda), Annales de Parasitologie Humaine et Comparee, 57, 593‑620
5 ) Bartlett, C.M. (1983): Zoogeography and taxonomy of Dirofilaria scapiceps (Leidy, 1886) andD. umformis (Price, 1957) (Nematoda: Filarioidea) of logomorphs in North America, Canad.
J. Zool., 61, 1011‑l022

6 ) Bartlett, C.M. (1987): The reptilian filarioid genus Foleyella Seurat, 1917 (Onchocercidae:
Dirofilariinae) and its relationship to other Dirofilariinae genera, Systematic Parasitology, 9,

43‑567 ) Chabaud, A.G. and Anderson, R.C. (1959) : Novel essai de classification des Filaires (super‑famille des Filarioidea) II., Annales de Parasitologie Humaine et Comparee, 34, 64‑87
8 ) Chabaud, A.G. and Bain, P. (1976): La lignee Dipetalonema. Nouvel essai de classification,
Annales de Parasitologie Humaine et Comparee, 51, 365‑397
9 ) Chabaud, A.G. and Choquet, M.T. (1953) : Novel essai de classification des Filaires (super‑famille des Filarioidea), Annales de Parasitologie Humaine et Comparee, 28, 172‑192
lO) Hennig, W. (1965): Phylogenetic Systematics, Annual Review of Entomology, 10, 97‑116ll) Lopez‑Neyra, C.R. (1956): Revision de la Superfamilia Filarioidea (Weinland, 1858). Revista
lberica de Parasitologia, 16, 3‑212

12) Maddison, W.P., Donoghue, M.J. and Maddison, D.R. (1984): Outgroup analysis and Parsi‑mony, Systematic Zoology, 33, 83‑103
13) Rodman, J.E., Oliver, M.K., Nakumura, R.R.. Mc Clammer J.U. and Bledsoe, A.H. (1984): A
taxonomic analysis and revised classification of Centrospermae, Systematic Botany, 9, 297‑323

27014) Swafford, D.L. (1985): PAUP Phylogenetic Analysis, Using Parsimony version 2.4, Illinois
Natural History Survey, Illinois
15) Wehr, E.E. (1935): A revised classification of the nematode superfamily Filarioidea, Proceed‑

ings of Helminthological Society of Washington, 2, 84‑88
16) Wiley, E.O. (1981): Phylogenetics: The Theory and Practice of Phylogenetic Systematics,

John Wiley and Sons, New York17) Yorke, W. and Maplestone, P.A. (1926): The Nematode Parasites of Vertebrates, Haffner
Publishing Company, London

Jpn. J. Trop. Med. Hyg., Vol. 20, No. 4, 1992, pp. 271‑281

271

BASIC STUDIES ON THE MONGOLIAN GERBILAS A SUSCEPTIBLE HOST TO FILARIAL INFECTION;
lgE‑LIKE ANTIBODY FORMATION AGAINSTDIROFILARIA IMMITIS ADULT WORM ANTIGEN
KAZUHIRO SHICHlNOHE*"' *, MASUMI SHIMIZUl' 4, KAZUYOSHI KAT02

NAOHIKO TAMURA3, SETSUKO TSUKIDATE4 AND KOICHIRO FUJITA'
Received August 6 1992/Accepted September 10 1992

Abstract: Antibody. production in Mongolian gerbils (Meriones unguiculatus) immun‑

ized with crude extract of Dirofilaria immitis adult worm was tested with passive
cutaneous anaphylaxis reaction. Immunized gerbils produced a long‑term binding, heat‑
labile antigen‑specific antibody which sensitized the rat skin. Those profiles were like anlgE antibody. In an intact gerbil, IgE‑like substance was detected in an immediate
intracufaneous reaction with anti‑rat lgE antibody. Mast cells representing meta‑
chromasia were confirmed in the skin tissue section of Mongolian gerbils stained with
Toluidine blue and were thought to be target cells for those anaphylactic reactions.

INTRODUCTION
The Mongolian gerbil (Meriones unguiculatus) is very frequently used for a host to
maintain some filarial parasites and an experimental model of filariasis because of easy
handling to care and high sensitivity to various filarial parasites such as Brugia spp., (Ash andRiley, 1970 a, b) Dipetalonemd viteae (Dalesandro and Klei, 1976) and Litomosoides carinii(Matsuda et al.. 1976). Despite of utility in a research of parasitology, information on

biological characteristics of the gerbil such as antibody fesponse to parasites is l!mited(Tomisato et al.. 1983; Farrar et a[.. 1991) and there is no report on antibody production
induced by immunization 'with a parasitic

ntigen in the gerbil.

The purpose of this study was to examine antigen‑specific antibody production in
immunized gerbils and ‑to identify presence of lgE‑1ike aritibody in an intact gerbil. We
carried out an immunization of gerbils with crude extract derived from Dirofilaria immitis
adult worm and an immediate intracutaneous reaction using sheep anti‑rat lgE antiserum todetect lgE‑like antibody in the gerbil.

1 Department of Laboratory Animal Science ( * corespondent author) and2 Department of Emergency and Critical Care Medicine, Nippon Medical School, 1‑1‑5 Sendagi,
Bunkyo‑ku, Tokyo ll3. Japan.

3 Department of Parasitology, Nippon Veterinary and Animal Science University, 1‑7‑1
Kyonan‑cho, Musashino, Tokyo 180, Japan.
4 Department of Medical Zoology, Faculty of Medicin , Tokyo Medical and Dental University,
1‑5‑45 Yushima, Bunkyo‑ku, Tokyo 113, Japan.

272

MATERIALS AND METHODS
Animals
Three to 5 month‑old Mongolian gerbils (JMS‑strain) of both sexes were used in thefollowing immunization with D. immitis (DD antigen, passive cutaneous anaphylaxis (PCA)
reactions for recipients and an immediate intracutaneous reaction for anti‑rat lgE antiserum.

These animals were supplied originally from Institute of,Medical Science, Tokyo University

in 1973 and were bred with sister‑brother matings under a conventional condition in ourlaboratory (Shimizu et al., 1990). Sprague‑Dawley (SD) female rats aged 9 weeks werepurchased from Saitama Experimental Animal Supply and were used as recipients of PCA
reactions and a positive control of the immediate intracutaneous reaction for anti‑rat lgEantiserum.

Immunization with D. immitis adult worm antigen in gerbils
Crude extract derived from DI adult worm was prepared by the method as previously
described (Fujita, 1975) and was used as DI antigen for immunization. Protein concentrationin DI antigen was estimated by the method of Lowry et al. (1951) . Experimental design ofimmunization is summarized in Fig. 1. Gerbils were randomly allocated to the 2 groups andwere immunized with an intraperitoneal injection of various doses of antigen mixed withAnimal: male and female 3‑5 month‑old Mongolian gerbils (JMS strain)
Antigen: Crude extract from Dirofilaria immitis adult worm
Immunization: lO, 100, 500 or 1,000 pg antigen with 8 mg alum in 0.5 ml saline i.p. peran animal
Booster: an equal dose of antigen to Ist immunization with an equal way.
Interval:Group l.
Ist immunization

3 weekl ' week

O

Group 2.
Ist immunization

PCA

boosterT

3 week2 weeko

Numbers of gerbils in each group:

Antigen dose
( pg/animaD

Group 1
Group 2

lO

100

500

1 , OOO

40

20

20

20

60

60

Figure 1 Experimental design of immunization.

273

8 mg alum in 0.5 ml saline per an animal at different intervals. In group l, 40 gerbils were

immunized with 10 pg antigen and 20 animals each were immunized with 100, 500 or 1,000 pg
antigen. One week later they were boosted with an intraperitoneal injection of an equalamount of antigen to the first immunization, and two weeks after the boost they were bledfrom the heart. In group 2, 60 gerbils each were immunized with 10 or 100 pg antigen. Two
weeks later they were boosted with an intraperitoneal injection of an equal amount of antigen

to the first immunization, and one week after the boost they were bled from the heart. Blood

samples from immunized gerbils were centrifugalized separately (not pooD and each serum
was stored at ‑ 20'C until PCA reaction.
Passive cutaneous anaphylaxis (PCA) reaction

Antibody in serum samples from gerbils immunized with DI antigen were tested withhomologous and heterologous PCA reactions using gerbils and SD rats for recipients. Dermalsites of gerbils and rats were sensitized with sera from immunized gerbils in a volume of 0.1
ml at 10‑fold‑dilution. They were challenged 4 or 72 hr later with intravenous injections of
1 mg DI antigen in 0.5 ml 1% Evans blue in saline into the saphenous vein in gerbils and 1.0
ml into the tail vein in rats. Thirty minutes after antigen administrations, recipients weresacrificed under ether‑anesthetization and were skinned to measure diameters of the reac‑
tions on the, inner side of the skin. A blue spot larger than 3 mm in diameter was regarded
as positive reaction. Positive sera were tested PCA reaction again after heat treatment at
56'C for 30 min.
Immediate intracutaneous reaction in gerbils for anti‑rat lgE antiserum

To investigate presence of an lgE‑1ike antibody in intact gerbils, the immediate
intracutaneous reaction for sheep anti‑rat lgE antiserum was carried out. Sheep anti‑rat lgEantisera (Miles Laboratory, Inc.) in 2‑fold serial dilutions in a volume of 0.1 ml were
inoculated intracutaneously to sites on the back skins of rats and gerbils. One mililiter and
0.5 ml 1% Evans blue solution were injected intravenously into the tail vein in the rat and into

the saphenous vein in the gerbil, respectively, immediately after inoculation with antisera.

After 30 min, areas of the blue spots were examined. The reaction in the rat was regarded
as a positive control and was compared to that in the gerbil.
Preparation of skin tissue sectlons of gerbils

The dorsal skins of gerbils were shaved and were quickly removed at the time ofsacrifice. Blocks of the skin tissues were fixed with 10% buffered formalin and embedded inparaffin. Skin tissue sections were stained with Toluidine blue and examined under a lightmicroscope.

RESULTS
PCA reaction
Table I gives numbers of positive samples from immunized gerbils of group I in PCA
reactions. 0‑23% and 5‑15% of serum samples showed positive reactions in heterologous
PCA reactions using rats for recipients after a 4‑hr‑ and a 72‑hr‑sensitization period,
respectively. There was no tendency to correlate between antigen doses and positive rates

274

Table I Posutive rates of sera from immunized Mongolian gerbils of group I in PCA reactions
PCA recipient

Antigen dose Sensitization

Mongolian gerbil

SD rat(pg/animaD period (hr)Numbers of samples
Numbers of samples positive
Positive

rate (%)
total positive total rate (%)
positive

lO

lOO

500

l , OOO

4

9

72

6

4

3

72

1

4

O

40
40

23

o

15

o

20
20

15

O

5

o

O

O

10

l

5

O

15

1

72

2

20
20

4

1

20

72

20

3

40
40

o

20
20

o

20
20

o

20
20

o

o

O

5

5

Table 2 Positive rates of sera from immunized Mongolian gerbils of group 2 in PCA reactions
PCA recipient

Antigen dose Sensitization

Mongolian gerbil

SD rat(pg/animaD period (hr)Numbers of samples
Numbers of samples positive
Positive

rate (%)
total positive total rate (%)
positive

10

lOO

4

7

72

1

4

5

72

13

60
60
60
60

12

o
O

60
60

o

2
8

o

60'

o

22

O

60

O

o

in samples from group I gerbils. In homologous PCA reactions using gerbils for recipients,
two samples represented positive reactions after a 72‑hr‑sensitization period.

Table 2 shows positive rates of samples from group 2 gerbils in PCA reactions. In
heterologous PCA reactions after a 4‑hr‑sensitization period, positive rates of samples fromgroup 2 gerbils immunized with 10 pg and of those immunized with 100 pg were 12% and 8% ,respectively. Positive PCA reactions with 72 hr of sensitization period were obtained in 2%
and 22% of each 60 samples from gerbils immunized with 10 and 100 pg antigen, respectively.
In homologous PCA reactions, positive reaction could not be observed.
Those positive samples in PCA reactions after a 72‑hr‑sensitization period were heatedat 56'C for 30 min and were assayed again. PCA positive reactions completely abolished inall samples after heat treatment (Fig. 2) .

Immediate intracutaneous reaction for anti‑rat lgE serum
Fig. 3a shows the immediate intracutaneous reaction for sheep anti‑rat lgE antiserum ina positive control of a rat. A 1,600‑fold dilution of anti‑rat lgE gave a positive reaction ina rat skin, whereas saline and normal sheep serum did not.
Fig. 3b represents a reaction for that experiment in an intact gerbil. In an intact gerbil,

also a 1,600‑fold dilution gave a positive reaction with a distinct blue spot, but saline and275(b) after heat inactivation(a)No. 69No. 69No. 14

No. 14i.

'=,* i, .*';

' >.{ ;j ･.･,*,

Figure 2 Passive cutaneous anaphylaxis with sera frorn Mongolian
gerbils immunized with crude extract of Dirofilaria immitis(DD worm in a rat skin. A l:lO dilution of sera were inoculated

intracutaneously. Animals were challenged by an intravenous
injection of DI antigen together with Evans blue dye 72 hr after

the sensitization. Samples (No. 69 and 14) gave positive
reactions (a). After heat inactivation at 56'C for 30 min, thesame samples failed to induce the reactions (b).

276s at i n e

X 1 600

normalx800

sheep serum

X400
X200

x50
x I OOa*sa,ineX 1 60(normal5heep serum

x800
X400
X200

X50
X I OO'd lb
Figure 3 Immediate intracutaneous reactions induced by sheep anti‑rat

lgE antiserum. Serial 2‑fold dilutions of antiserum prepara‑tion, saline and normal sheep serum were inoculated
intracutaneously into a rat (a) or into a normal Mongolian
gerbil (b) , followed by an intravenous injection of Evans bluedye. Even a 1,600‑fold dilution of antiserum gave positive
reactions both in a rat (a) and in a Mongolian gerbil (b),whereas saline and normal sheep serum did not.

277

Figure 4 Histological findings in the skin tissue section of a Mongolian
gerbil stained with Toludine blue. Mast cells representing
peculiar metachromasia were idenfied.

normal sheep serum failed to induce the reactions.
Histological findings of the skin tissue of gerbils

Fig. 4 gives a photograph of the skin tissue section of the gerbil stained with Toluidine
blue. Mast cells representing peculiar metachromasia were identified in the skin tissue of thegerbil.

278

DrscussloN
This is a preliminary report on antigen specific antibody induced by immunization with

DI worm antigen in the Mongolian gerbil. Immunized gerbil produced a long‑term binding
heat‑labile antibody that sensitized the rat skin. These profiles were similar to murine lgE(Mota and Wong, 1969; Ovary et al., 1975; Watanabe and Ovary, 1977). But the antibody
from gerbil was less homocytotropic which was on6 of peculiar characteristics of lgE andonly 2 samples from a total 220 immunized gerbils represented positive in a long‑termhomologous PCA reaction. The cause may be that the gerbil is hard to produce lgE‑likeantibody by nature or it has a large individual difference because it has not been controlled
genetic characteristics of this species for a laboratory animal such as a inbred strain. Hosts

produce an antigen‑specific antibody during the course of helminth infection (Mota et al.,
1969; Kojima and Ovary, 1975; Watanabe and Ovary, 1978; Rousseaux‑Prevost et al., 1979;
Oikawa et al., 1981). On the gerbil infected with Brugia spp., production (Tomisato et al.,1983) and down regulation (Farrar et al.. 1991) of an lgG antibody, a protective resistanceto reinfection (Yates and Higashi, 1985; Kazura et al., 1986; Klei et al., 1990) and reductionof cellular responses (Lammie and Kats, 1983; Klei et al., 1981, 1988, 1990) have beenreported. Those studies indicated that chronic Brugia spp. infection induced the gerbil a stateof immunosuppression. One of the cause of high sensitivity of the gerbil to some filarial
parasites may be attributed to the immunosuppression. Difiiculty of lgE‑like antibody
production in the gerbil in this study may also support susceptibility of the gerbil to various
parasites.

In an intact gerbil, a present study strongly suggested a presence of lgE‑like substancethat induce the immediate intracutaneous reaction with anti‑rat lgE antibody. It has been

unknown how much homology of lgE between the rat and the gerbil is. But lgE‑like
substance of the gerbil was thought to have cross reactivity with rat lgE and to be specificallybound to anti‑rat lgE antibody because normal sheep serum and saline failed to induce
hypersensitivity of the skin. It is generally accepted on mice, rats and human that lgE has
high affinity for mast cells and basophil granulocytes and the reaction of cell‑bound lgE witheither antigen or anti‑IgE triggers the release of chemical mediators from those cells(Kulczycki and Metzger, 1974; Ishizaka and Ishizaka, 1975; Austen, 1979; Sterk and Ishizaka,1982). We could speculate that lgE‑1ike substance of the gerbil also bound to mast cells inthe skin, induced the release of chemical mediators from mast cells through almost samemechanisms as those of mice or rats, and as a result of those anaphylactic reactions, we could

observed positive reactions on the skin. It is now well established that mast cells andbasophils also carry on their surface receptors capable of interacting with lgG. For example,
lgGl in mice (Tigellar et al., 1971) or in guinea pigs (Ovary, 1986) , IgG2* in rats (Morse etal., 1968) or lgG2 in human (Assem and Turner‑Warwick, 1976) sensitizes target cells foranaphylactic reactions. In gerbils, we could not detect lgG which was implicated in ana‑
phylactic reactions in this study.

In the present study, we could induce antigen‑specific antibody in the gerbil by immuniza‑tion with DI worm antigen and confirmed a presence of lgE‑like substance and mast cells in
an intact gerbil. We previously reported that the gerbil has also basophilic granulocytes(Shimizu et al.. 1991) which were known to be lgE‑binding targets as well as mast cells inmice or rats in peripheral blood. We showed that the gerbil had enoumous potentialities of279

a model to analyse host‑parasite relationship including lgE production and anaphylactic
reactions.

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unguiculatus, with notes on infection in other rodents, J. Parasitol., 56, 962‑968

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3 ) Assem, E.S.K. and Turner‑Warwick, M. (1976) : Cytophylic antibodies in bronchopulmonary
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and Mongolian jirds by Dipetalonema viteae infections, Trans. R. Soc. Trop. Med. Hyg., 70,

534‑5356 ) Farrar, R.G.. Klei. T.R., McVay. C.S. and Coleman, S.U. (1991): Qualitative characterizationof antibody responses to single and multiple Brugia pahangi infections in jirds, J. Parasitol., 77,

718‑7267 ) Fujita. K. (1975): Separation of Dirofilaria immitis allergen from the lgG‑induced antigen,Jap. J. Med. Sci. Biol., 28, 139‑149
8 ) Ishizaka, T. ahd Ishizaka, K. (1975): Biology of immunogloblin E. Moledular basis of reaginic

hypersensitivity, Prog. Allergy, 19, 60 '9 ) Kazura, J., Cicirello, H, and McCall, J.W. (1986): Induction of protection against Brugia
malayi infection in jirds by microfilarial antigens, J. Immunol., 136, 1422‑1426

lO) Klei, T.R.. Enright, F.M., Blanchard. D. and Uhl, S. (1981): Specific hyporesponsive
granulomatous tissue reactions in Brugia pahangi‑infected jirds, Acta. Tropica, 38, 267‑276ll) Klei. T.R., Enright, F.M., McDonough, K. and Coleman, S. (1988) : Brugia pahangi:
Granulomatous lesion development in jirds following single and multiple infections, Expl.
Parasitol., 66, 132‑139

12) Klei, T.R., McVay, C.S.. Dennis, V.A., Coleman, S.U.. Enright, F.M. and Casey, H.W. (1990):

Brugia pahangi: Effects of duration of infection and parasite burden on lymphatic lesion
severity, granulomatous hypersensitivity, and immune responses in jirds (Meriones un‑
guiculatus) , Expl. Parasitol., 71, 393‑405
13) Kojima. S. and Ovary, Z. (1975): Effect of Nippostrongylus brasiliensis infection on anti‑haptenlgE antibody in the mouse. II. Mechanism of potentiation of the lgE antibody response to aheterologous hapten‑carrier conjugate, Cell. Immunol., 17, 383‑391
14) Kulczycki, A. Jr. and Metzger, H. (1974) : The interaction of lgE with rat basophilic leukemia
cells. II. Quantitative aspects of the binding reaction, J. Exp. Med., 140, 1676‑1695
15) Lammie. P.J. and Katz, S. (1983): Immunoregulation in experimental filariasis II. Responses
to parasite and non‑parasite antigens in jirds with Brugia pahangi. J. Immunol., 130, 1386‑1389
16) Lowry, O.H., Rosebrough, N.J., Fan, A.L. and Randall, R.J. (1951) : Protein measurement with

Folin phenol reagent, J. Biol. Chem., 193 265‑275 ,17) Matsuda H.. Takaoka, M. and Tanaka, H. (1976): Effect of diethylcarbamazine on
microfilariae of Litomosoides carinii in jird, Meriones unguiculatus. Jpn. J. Parasitol., 25, 94‑98

18) Morse, H.C., Bloch, K.J. and Austen, K.F. (1968): Biologic properties of rat antibodies. II.

Time‑course of appearance of antibodies involved in antigen‑induced release of slow reacting

280

substance of anaphylaxis (SRS‑A). Association of this activity with lgGa, J. Immunol. 101,
658‑66319) Mota. I., Sadun, E.H.. Bradshaw, R.M. and Gore, R.W. (1969): The immunological response ofmice infected with Trichinella spiralis. Biological and physico‑chemical distinction of two
homocytotropic antibodies, Immunology, 16, 71‑81
20) Mota, I. and Wong, D. (1969): Homologous and heterologous passive cutaneous anaphylactic
activity of mouse antisera during the course of immunization, Life Sciences, 8, 813‑820 '21) Oikawa, Y., Ikeda, T. and Fujita, K. (1981): IgE antibody response in rats infected with
Litomosoides carinii. Trop. Med., 23, 149‑157
22) Ovary, Z.. Caiazza, S.S. and Kojima, S. (1975): PCA reactions with mouse antibodies in miceand rats, Int. Archs Allergy Appl. Immunol., 48, 16‑21

23) Ovary. Z. (1986) : Passive cutaneous anaphylaxis. In. Handbook of Experimental Im‑
munology, 4th ed., weir, P. M. ed., Blackwell Scientific Publications London, 33.1‑33.9

24) Rousseaux‑Prevost, R., Chassoux, D., Bazin, H, and Capron, A. (1979): Serum lgE Ievels inrats infected with Dipetalonema viteae L3 Larvae, Clin. Exp. Immunol., 38, 389‑393
25) Shimizu, M., Shichinohe, K., Tsukidate, S. and Fujita, K. (1990): Basic studies on the
Mongolian gerbil as a susceptible host to filarial infection; Comparative studies on growth andreproduction among boat color mutants and genetic analysis of coat colors, Japan. J. Trop.
Med. Hyg., 18, 301‑310
26) Shimizu, M., Shichinohe, K., Tsukidate, S. and Fujita. K. (1991): Basic studies on the

Mongolian gerbil as a susceptible host to filarial infection; Comparative studies onhematological features between the wild‑colored gerbil and the coat color mutants, Jpn. J.
Trop. Med. Hyg., 19, 331‑338
27) Sterk, A. and Ishizaka, T. (1982): Binding properties of lgE receptors on normal motise mast
cells, J. Immunol., 128, 838‑843

28) Tigelaar, R.E., Vaz, N.M. and Ovary, Z. (1971): Immunoglobulin receptors on mouse mast
cells, J. Immunol., 106, 661‑672

29) Tomisato. M., Nakajima, Y., Nariuchi. H. and Nogami, S. (1983): Detection of lgG antibodies
in Mongolian jirds infected with Brugia pahangi by enzyme‑linked immunosorbent assay, Jap.
J. Parasit., 32, 43‑54

30) Watanabe, N. and Ovary, Z. (1977): Antigen and antibody detection by in vivo methods: are‑evalutation of passive cutaneous anaphylactic reactions, J. Immunol. Meth., 14, 381‑390

31) Watanabe, N. and Ovary, Z. (1978): Enhancement of lgE antibody production in AKR mice,
Int. Archs Allergy appl. Immun., 57, 554‑559
32) Yates, J. and Higashi, G. (1985) : Brugia malayi: Vaccination of jirds with 60cobalt‑attenuatedinfective stage larvae protects against homologous challenge, Am. J. Trop. Med. Hyg., 34,
1132‑1137

281

フィラリア感染好適宿主としてのスナネズミの基礎的検討
一犬フィラリア虫体粗抗原によって誘導されたIgE様抗体一
七戸 和博1・ ・清水

眞澄1・4・加藤一良2・

田村直彦3・月舘説子4・藤田絃一郎4

フィラリア感染の実験室内好適宿主であるスナネズミ（Molgolian

gerbi1；〃i8吻η8s

観一

8㍑加観％s）を，犬フィラリア（D伽碩彪吻加雁漉）虫体より抽出した粗抗原によって免疫し，抗体産生について受身皮膚アナフィラキシー（PCA）反応を用いて検索した。免疫したスナネズ
ミの血清中には，ラットを被検動物とした72時間PCA反応で陽性を呈し，56。C30分間の熱処理によって不活化される抗原特異的抗体，すなわちIgE様抗体が検出された。
正常ズナネズミのIgE様抗体を検出するために，抗ラットIgEヒツジ抗体に対する，即時型皮内反応を行った。スナネズミの皮膚もラットと同様に，1，600倍希釈抗体に対して明瞭な陽性反応を示したことから，正常スナネズミにもIgE様物質の存在が示唆された。
正常スナネズミの皮膚に，トルイジン・ブルー染色でメタクロマジーを呈する肥満細胞の存在が確認され，上記の抗原抗体反応の場であると考えられた。

日本医科大学 実験動物管理室（＊別冊請求先 〒113東京都文京区千駄木1−1−5）
同 救急医学教室
日本獣医畜産大学獣医寄生虫学教室 〒180東京都武蔵野市境南町1−7−1
東京医科歯科大学医学部医動物学教室 〒113東京都文京区湯島1−5−45

Jpn. J. Trop. Med. Hyg., Vol. 20, No. 4, 1992, pp. 283‑290

283

BACTERIAL DIARRHOEAS IN JOS, NIGERIAAGATHA ANI , *, MOTOHISA TAKAHASHI', HARUO SAIDA3,
HIROKAZU TANIGUCHI', TOSHIYUKI TAKAHASH15 AND MAROTO SAT06
Received August 20 1992/Accepted September 16 1992

Abstract: In a 4 year study from October 1983 to March 1987, in Jos, Nigeria,bacterial enteric pathogens were isolated from 27.0% of 1,137 children aged 0‑5 years who
were clinically diagnosed for acute diarrhoea. A similar investigation was also carried out

on apparently healthy children of primary school age (7‑16 years), who were on regularschool attendance. Eight different primary schools located in the urban and rural areas ofJos, were selected for this phase of the study. The 1,468 children examined in the lattergroup had a total infection rate of ll.9% . Though the children were considered to beapparently healthy, 25.6% of them reported a history of diarrhoea, Iasting between 1‑21
days; 12.7% of these were bacterial positive as opposed to 11.6% for the non diarrhoeal
grou p.

In yet a third phase of the study, a total of 39 different households, predominantly ofadult population were investigated for the presence of common organisms among mem‑bers of the same family. Enteropathogenic Escherichia coli (EPEO serovar 0128:K67 was
isolated from 4 of 14 members of one family, while EPEC serovar 028:K73 was isolated
from 3 of 7 members of another family including 2 cases of multiple infections.

Some of the 48 strains of EPEC out of 130 isolates, although H antigen was not
examined, could possibly belong to EHEC (VTEC: verocyto‑toxin producing E. coli)
which are thought to be one of the causative agents of haemorrhagic diarrhoeae as wellas hemolytic uremic syndrome which are severe illnessess.

INTRODUCTION
Diarrhoeal diseases of bacterial aetiology continue to be a global concern. High rates of
infantile morbidity and mortality have been reported, particularly in developing countries(Ronde and Nerthrup, 1976; Barma, 1981) .

The reason why infants, and not adults, remain the high risk group could readily be
attributed to poor hygenic standards of the adult caretakers in addition to the immature
1

2

Depertment of Medical Microbiology, University of Jos. P.M.B. 2084, Jos, Nigeria ( * Corre‑
spondent author)
JICA Officina en Chile. Casilla 16137, Correo 9. Santiago, Chile4

1‑188, Mukaikurisaki, Uchinada‑machi, Kawakita‑gun, Ishikawa 920‑01, Japan
Animal Research Center, Faculty of Medicine, Tokyo Medical and Dental University, 1‑5‑45,

5Bunkyo‑ku, Tokyo 113, Japan
8‑1‑3‑403, Takashimadai, Kana awa‑ku, Yokohama 221, Japan

3

6

Library, The Tokyo Metropolitan Research Laboratory of Public Health, 3‑24‑1, Hyakunin‑cho, Shinjuku, Tokyo 169, Japan284

immune status of the children.
The present study reports on symptomatic and asymptomatic subjects with total infec‑

tion rate higher in the asymptomatic adult group.
RePorts indicating some adult Nigerian's staple meals as having antidiarrhoeal prop‑
erties were suggestive to us as a contributing factor for the higher youth‑adult asymptomatic
carriage rates.

MATERIAL AND METHODS
Subject: Children of 0‑5 years age group were attended to in the wards, O.P.D and the Child
Health Clinic of Jos University Teaching Hospital, while the school children and adults wereattended to in their schools and homes respectively.
Materials: Stool amples were collected in each case, into Cary‑Blair's transport medium.

Transportation to the laboratory and analysis were done within 24 hr of collection.

Culture: A11 stool specimens were inoculated on to; SS, DHL, TCBS and Skirrow's
Campylobacter selective solid media for primary isolations. Selenite broth (for Salmonellaspp.) and alkaline peptone water (for Vibrio spp.) were also used as enrichment broth.
Cultures were incubated at 37'C for 18‑24 hr, while Campylobacter cultures were incubated at
42'C for 48‑72 hr.

Biochemical identifications: Suspect colonies were inoculated on to; triple sugar iron agar
(TSI) , Iysine indole motility agar (LIM) , Sirnmons' citrate agar and Christensen's urea, fortentative identification of; Salmonella, Shigella. E. coli. Vibrio. Aeromonas and Yersinia(Lennette et al., 1983).

Oxidase positive colonies from the Campylobacter culture, showing typical Gram negative

spira or coccoid forms on microscopic examination were biotyped according to standard
methods (Lennette et al., 1983).
Serotyping: Salmonella, Shigella. EPEC, Yersinia and Vibrio species were examined by slide
agglutination procedure, using overnight pure growth of respective organisms on non‑selec‑

tive solid media. Antisera were obtained from Denka Seiken, Japan.
ETEC LT assay: The method is described briefly.

The Biken LT Assay Kit (Biken, Osaka, Japan) was used for identification of LT
producing strains of E. coli. Biken Agar was melted and placed in 15 ml amounts into 90 mm
plastic petri‑dishes. Each Biken Agar plate was appropriately inoculated with four different
cultures of E. coli, and incubated at 37'C for 48 hr.
Polymyxin B disc of 200 IU was carefully placed on each colony to improve intracellularrelease of LT. A hole was punched in the centre of the plates and incubation repeated for 5‑6

hr. 20 pl of LT antiserum was placed in the central well. Observation was made for
precipitin lines after incubation at 37'C for 24, 48 and 72 hr.

RESULTS
Twenty‑seven per cent of children aged 0‑5 years with clinically diagnosed diarrhoeal
disease were found bacteria positive, as against 11.9% for primary school children of ages 7‑

16 years and 12.7% for family units including adults respectively (Tables l, 2, 3). A11 theknown conventional diarrhoea‑associated bacteria isolated from the clinically diagnosed

285

Table 1 Infection rate of enteropathogenic bacteria in children 0‑5 yrs of Jos, Nigeria
No. ofcases

Sourceexamined
Pediatric

220

Wards
G.O.P.D.

525

C.H.C.

392

Total

l , 137

No, ofNo. of strains isolated/total case (%)

positive

cases

Shig.

EPEC

Sal.

Vib rio

Cam p y.

Others

75

24

13

14

10*

12

(34 . 1)

(10. 9)(5 . 9)(6 . 4)(O . 9)(4 . 5)(5. 4)

146

48

40

12

3

40*

3

(27. 8)(9. l)(7 . 6)(2 . 3)(O. 6)(7. 6)(O. 5)

o

31*

O

(o)

(7. 9)

(O)

5
(0.4)

81*

15

(7 . l)(1 . 3)86

23(17. 6)(5 . 9)

25
(6.4)

7
(1.8)

307

95

78

33

(27.0)(8.4)(6.9) (2.9)* : Estimate No. Actual No, are 8/172, 34/439, 17/214.

Shig.: Shigella. Sal.: Salmonella, Campy..' Campylobacter 'Others: Klebsiella pneumoniae. Proteus 1 eorganii, Staphylococus aureus etc.

Table 2 Bacterial enteric pathogens isolated from children of 8 different
primary schools located at the urban and rural areas of Jos, Nigeria
N o. of isolates

Bacteria

with diarrhoea
376* (25.6)

EPEC

10

(2 . 7)C. jejuni

18(4 . 8)Shl el la

5(1 . 3)

Salmonella

8(2 , l)ETEC (LT)5(1 , 3)

A. hydrophila

2

(0.5)

Y. enterocolitica

O

Total

48 (12.7)

(%)

Total

without diarrhoea
1,092* (74.4)

1 , 468*45(4 . 1)55(6. 8)

40
19(3 . 7)58(8 . 4)(1 . 7)24(3. 1)

17(1 . 6)25(3. 7)

5(1. 3)

4

(0.4)

6

(O . 9)1(O . 1)l(O . 1)126 (11.6)

174 (11.9)* : No. of children examined

Table 3 Bacterial enteric pathogens isolated from 39 family units from 2
villages in the rural area of Jos, Nigeria

No. of isolates (% )Bacteria

with diarrhoea

without diarrhoea

35*

186*

EPEC

2

(5 . 7)

8(4 . 3)

Total
221*
lO

(4 . 7)C. jejuni

3(1 . 6)

3(1 . 3)

Shigel la

lO

(5.4)

10

(4 . 6)

Salmonella

2(1 . O)

2(O . 9)3(1 . 6)

3(1 . 4)ETEC (LT)A. hydrophillaY. enterocolitica

Total* : No. of cases examined.

2 (5.7)26 (14.1)

28 (12.7)

286

Table 4 Cases of multiple isolations from primary school children and family unitsof Jos, Nigeria

From family units

From primary schoolwith diarrhoea

without diarrhoea

EPEC Oll4:K90

Shigella flexneri

EPEC 028:K73*

C, jejurd

Salmonella spp.

Salmonella spp.

with diarrhoea

without diarrhoea

EPEC 027:K+
C. jejuni

EPEC 028:K73*

EPEC 0127:K63
EPEC 0148:K+

Shigella flexneri

LT (+)
Shigella boydii 14

EPEC 026:K60

LT (+)

C. jejuni

EPEC 0127:K63
C. jejuni

C. jejwai

Salmonella 04

EPEC 025:Kl
Salmonella 03, 10* : Isolated from members of the same family unit.

Table 5 Serovars of enteropathogenic E. co li isolated

OK Serovar
O1:K51
O111:K58
O114:K900124:K72
0124:K91
0125:K700126:K71
0127:K630128:K670142:K+
0148:K+
0159:K+
025:K1
026:K60
027:K+
028:K73
044:K74
044:K77055:K59
06:K15086:K61

0‑5 yrs

(H)
(H)
(D

Primary school
children35(1) *

72

5lAdults

l

1

2

2

5

(H)

5

5(1) *l5

2

6(1) *

14 (1) *l (1) *

3

(T)

4

1(1) *

(T)

(T)

(H)

1

2

6

6
4 (1) *

(D

l

O

3

4
1

4

(H)
7

6(1)

Total 130
(T) : (ETEO;(1) *:(1):(EIEC); (H):(EHEO

No. of isolates from diarrhoeal cases.

287

cases were also found in the apparently healthy population studied except for Vibrio cholerae
O1 ( V. cholerae), of which a total of 5 (0.4%) cases were isolated and were all identified as

non‑agglutinable serovar. Aeromonas hydrophila and Yersinia enterocolitica were isolated
from some of the primary school children and not frorn the adults and infants groups (Tables
1, 2, 3).

Multiple isolations were also indicated (Table 4) , EPEC seems to be the predominating
pair in each of the cases (8 of 11 cases were paired with EPEO . Tables 5 and 6 presents thedifferent bacterial serovars and serogroups isolated from the study.

Table 6 Serovars or serogroup of Salmonella and Sht ella
isolated

0‑5
yrs

Serovar or serogroup
Shigella flexneri

la

2

lb
2a
2b
3a

18

Primaryschoolchildren

Adults

2

8

1

4
6

2

5
5

2

6

14

Shl el la dysenteriae

3

2
3

4

4
7

2
1

2

8

1

5
2

Shigella boydii

2
5

l

1

1

7

10

4

14

6

15

2

Shigella sonnei

9

Shigella spp.

1

5

Salmonella typhi

2

1

Saltnonella 04
07
08
09

13

3
5

3
2

O1, 3, 19

03, 10
Salmonella spp.

l

4

9
12

19

6

288

DlscUssloN
The present study suggests that enteric infections of bacterial aetiology may often
present with mild to asymptomatic conditions in the youth and adult populations in Jos,
Nigeria (Tables 2, 3). Our suggestion is further strengthened in our study by the finding of
the primary school children who were still able to carry out their routine school activities inspite of the fact that 25.6% of them were found to be diarrhoeal positive. The figure wasderived from questionaire report only; the stool samples were, however, formed in consis‑
tency with little or no pathological findings on macroscopical examination. 12.7% of thesewere bacterial positive. It could not be ascertained within the scope of this study as topossibility of any associated immune conditions. However, some Nigerian adult staple meals,such as Gari, Cassava and some grains have been reported to have antidiarrhoeal properties
similar in action to kaolin (Abosede, 1987; Ukunwe, 1987). It is possible that the Nigerian
food quality may be largely responsible for the asymptomatic excretions of organisms. An
infection rate of 27.0% in the 0‑5 age group was of great concern to us. The adults who takecare of these children may be found among asymptomatic pathogen carriers and their role incontributing to such a high infection rate is noteworthy. A number of vectors and mecha‑
nisms may be involved but the poor standard of hygiene in handling children and their feeding

appear to be predominant.
Serovars of E. coli, reported to be associated with: enterotoxogenic (ETEC), enter‑oinvasive (EIEO , and enterohaemorrhagic (EHEO properties (Levine, 1987) were also
isolated, although we have conventionally grouped all as EPEC (Table 5) . As presented on
the Table the cases of; serovars O1:K51 (EHEO ; 0148:K+ (ETEC) and 0127:K63; 0128:K67(EHEO; 027:K+ and 0159:K+ (ETEO where only 1/5, 2/15, 1/6, 1/8, 1/4 and 1/1 wererespectively isolated from diarrhoeal cases of the primary school children and adults but
infants who were clinically diagnosed for acute diarrhoeae are noteworthy.
While we could not evaluate the pathogenic role of E. coli serovars isolated from thisstudy to ascertain whether they were in each case responsible for the diarrhoea, particularlyin the non‑infant population, we feel obliged to consider their isolation from the adults withor without diarrhoea as a potential source of hazzard for the infants, particularly in areas oflow socio‑economic standards as evidenced in the present study area.
A recent massive outbreak of the kindergarden infantile diarrhoeae caused by EHEC(VTEC: verocytotoxin producing E. coli) 0157:H7 in Japan in 1990 (Ito, 1991) resulting in thehospitalization of 34 pupils and 2 deaths has led us to reappraise our data on the isolation of

EPEC in Nigeria. As shown in Table 5, although we did not examine H antigen, some of the
48 strains out of 130 isolates (36%) could possibly belong to EHEC (VTEO . The majorityof them except 0128:K67 were derived from 0‑5 year old infants and primary school children.
O'Brien et al. (1983) reported that VT (VTD produced by E. coli 026:H11 as well as0157:H7 was the same as Shiga‑toxin produced by S. dysenteriae 1, thus making clear the
homogeniety between VT of E. coli and Shiga‑toxin. It is well known in North America thatthe toxin produced by 0157:H7 degenerates and kills Verocells and clinically causes haemorr‑
hagic diarrhoeae developing often haemorrhagic uremic syn rome thus becoming a severe
illness.

These facts remind us of the complaints of the pupils as reported by school teachers while

engaging in the field surveys of the infantile diarrhoeae in Nigeria. Some school teachers had

289

reported that some children were su ering from pains at the lower back (around kidneyarea) , and also passed red urine. Unfortunately we had no antiserum to 0157:H7 at that time

and we were unable to pursue the issue further. The pupils from whom no bacterial
pathogens were isolated inspite of heavy hemorrhagic diarrhoeae and hemolytic uremia may
be considered to be candidates infected with 0157:H7. It should be noted, however, that apartfrom causing diarrhoea, often a common and serious disease in Nigeria, EHEC (VTEO
might cause many other diseases. When viewed from these angles, it seems very importantand also urgent that the study of the aetiology of infantile diarrhoea be resumed in Nigeria.

Findings from our study lend support to this recommendation.
Vibrio species was not isolated from the apparently healthy group, but from the 0‑5 age
group (0.4%) who presented clinically diagnosed acute diarrhoea, all 5 strains isolated were

non agglutinable (NAG) .
Of interest to note that V. cholerae Ogawa serovars are currently being isolated fromclinical cases reported between April‑July, 1991, at the Jos University Teaching Hospital. A

number of deaths have been reported in Jos and environs (unpublished data) .

ACKNOWLEDGEMENTS
This study was jointly sponsored by University of Jos and Japan International Coopera‑tion Agency (JICA). We acknowledge Prof. A.C. Ikeme, the Dean of Medical Sciences,
University of Jos. Mr. R.A.O. Shonekan, the Head of the Department of Microbiology and Dr,

Hiroshi Takahashi, the Team Leader of JICA in Jos. We also thank Prof. 0.0. Ogunremi,
Depertment of Psychiatry, University of llorin, Nigeria; visiting scientist, Tokyo Institute of

Psychiatry, Tokyo, for correcting the manuscript.

REFERENCES
1 ) Abosede, O.A. (1987): Traditional interventions for diarrhoeas in Nigeria: Views of Commu‑
nity Health Personells, Proc. Nigeria (UniJos)/Japan Joint Conference, Jos., 143‑146

2 ) Barma, D. (1981): The WHO global diarrhoeae disease control (CDO programme, In S.O.
Emejuaiwe, O. Ogunbi and S. Sonni (Eds.) 6th Intemational Conference on Global Impact ofApplied Microbiology., 405‑410. Academic Press, London
3 ) Ito, T. (1991): The bacteriological feature of Vero cell cyto toxin producing E. coli and theinfectious disease. Media Circle, 36 (5), 149‑161 (in Japanese)4 ) Lennette, E.H., Albert, B., William, J. and Joseph, P.T. (1983): Enterobacteriaceae. 3rd. ed.

American Society for Microbiology, Washington. D.C.
5 ) Levine, M.M. (1987): Escherichia coli, that cause diarrhoea, enterotoxigenic, enterohaemor‑
ragic and enteroadherent, J. Infect. Dis. 155, 377‑388
6 ) O'Brien, A.D., Lively, T.A., Chen, M.E., Rothman, S.W. and Formal, S.E. (1983): Escherichia

coli 0157:H7 strains associated with haemorrhagic colitis in the United States produce a
Shigella dysenteriae I (Shiga) Iike cytotoxin, The Lancet, March, 26, 702
7 ) Ronde, J.E. and Nerthrup, R.S. (1976): Taking science where the diarrhea is, acute diarrhea

in childhood., 339‑366, Ciba Foundation Symposium, 42, Elsevier‑Excerpta Medica
8 ) Ukunw , E.O. (1987): Oral dehydration therapy with manioc, Proc. Nigeria (UniJos)/Japan
Joint‑Conference. Jos. 140‑142

290

ナイジェリア国ジョスに於ける細菌性下痢症について
Agatha ANI1・高橋 基久2・才田 春夫3・
谷口 博一4・高橋 利幸5・佐藤 麿人6

1983−1987年の4年間にわたる，ナイジェリア国ジョスにおける腸内病原菌を対象とした調査において，臨床的に急性下痢症と診断された0−5歳児1，137症例から，307株（27．0％）の病原菌が分離された。同様な調査は，8つの農村，および市内の小学校における健康通学児童（・7−16歳，1，468名）についても行われた。申告により下痢病歴のある児童は25．6％で，菌の検出率は12．7％，下痢病歴のない者からの検出率は11．6％であった。

この様にナイジェリア児童の保菌者率は，先進国に比較すると大変に高い。一方，成人を含む39家族については，家族内感染を想定して同じような調査が行われた。1家族14人中4人から0128：K67（EHECの可能性あり）が分離され，他の家族では7人中3人が028：K73が分離され，うち2人は多重感染をしていた。最近（1990年）の日本における出血性下痢性大腸菌EHEC，0157：

H7に因る幼稚園児の集団下痢発生は，34人の入院患者と2人の死者を生じた。このことは，我々のナイジェリアにおけるEPEC分離データの再考慮を促した。その結果，たとえH抗原は調べなかったにせよ，分離されたEPEC130株中48株（36．9％）のうち，いくつかはEHECの可能性がある。残念なことに，当時我々は0157：H7に対する抗血清を入手出来なかったので，相当数のこの菌を取り逃がしたことが考えられる。当時，小学校の教師から子供達の中には，背中（腎臓部領域）の痛みを訴え，赤い小便をする者がいて，健康状態も良くないと言われたことを思いだすと，今になって了解できるものがある。即ちナイジェリアにおいては，相当数の児童がEHEC（VTEC）に感染し，健康が阻害されていると予想され，この新しい観点にたっての再調査が，緊急に必要と考えられる。

1

Depertment ofMedicalMicrobiology，FacultyofMedicalSciences，University

2084，Jos．Nigeria
JICA

O伍ce

en Chile，Casillal6137，Correo9，Santiago，Chile〒920−01石川県河北郡内灘町向栗崎1−188
東京医科歯科大学医学部実験動物施設（〒113東京都文京区湯島1−5−45）〒221横浜市神奈川区高島台8−1−3−403
東京都立衛生研究所図書室（〒169東京都新宿区百人町3−24−1）

ofJos．PM．B。

291

日熱医会誌，第20巻 第4号 1992年 291−297頁

大阪空港検疫所におけるインド，ネパール長期旅行者
下痢症患者からのランブル鞭毛虫検出成績
木村

明生1・＊・峯川

楠井

好一1・池田長繁2・下入佐賢治3・善久4・松本 泰和5・中林 敏夫6

平成4年9月14日受付／平成4年10月5日受理

はじめに発熱等を申告した旅行者のうち，医師の診察を受け，病原細菌検出を目的として検便を実施した者

近年のわが国と諸外国との交流の増加により，の中で，インドまたはネパールのいずれか，ある

海外旅行者数も年々増加しつつあり，1991年においは両国での滞在期間の合計が10日以上の旅行者

ける全国の空港検疫所における検疫機数および検を，ランブル鞭毛虫感染検査の対象者とし，以下疫人数は，厚生省生活衛生局食品保健課検疫所業の方法で検便を実施した。

務管理室資料によれば，8万機，1，700万人にも達

患者糞便約19を10mJのMIF固定液に投入している。このような状況を背景に，コレラや赤して固定・染色後，少量をスライドグラスに塗抹，痢をはじめとする腸管感染症の輸入症例の増加が鏡検した。また糞便の残量をMGL法により処理指摘されてきた（阿部ら，1981；山田ら，1983；宮した後，沈渣をヨード・ヨードカリ液で染色し鏡田ら，1990）。

検した。なお本報告で用いたランブル鞭毛虫陽性

著者等も同様の観点から，1983年から3年間に，大阪空港より入国した海外旅行者下痢症患者者について，その発症時および検疫時の症状を調べると共に，細菌学的検査を実施した。

についての腸管原虫感染の実態調査を行い，特にインド，ネパールヘの長期旅行の下痢症患者の約14％にランブル鞭毛虫感染が見られることを明ら成績

そこで今回は，インド，ネパール長期旅行者の1．調査対象者
1986年1月から1991年12月までの6年間におランブル鞭毛虫感染状況について，1986年より

ける，ランブル鞭毛虫検出を目的とした調査対象

1991年までの6年間に，同地域への長期旅行者下者は692名で，うち男性は554名（80．1％），女性は

痢症患者を対象とした継続調査を実施すると共に，138名（19．9％），平均年齢は27．4歳であった。各

その成績を解析し若干の疫学的考察を加えた。

年の病原細菌検出を目的とした検便数（総検便数）

かにした（木村ら，1987）。

とランブル鞭毛虫調査対象者数の割合（検査率）

を表1に示した。との表で明らかなように，総検材料と方法
入国時に，過去2週間以内の下痢，嘔吐，腹痛，

便数の中での調査対象者の占める割合は，年々減少する傾向が見られた。

大阪府立公衆衛生研究所ウイルス課（＊別冊請求先：〒537大阪市東成区中道1丁目3−69）
大阪検疫所
名古屋検疫所
長崎検疫所
大阪空港検疫所
藤田保健衛生大学医学部寄生虫学教室

292

Table1

Total number
positive

Total

No．of

cases

at

Osaka

examinees

No．examinedfor

Examinationrate（％）

Airport Quarantine

in1986−1991

1987

1988

1989

1990

1991

Total

1，373

1，871 1，801

1，583

9，757

1，583

1，546

132

205

148

107

69

31

692

9．6

11．0

8．2

6．8

4．5

2．0

7．1

O．乙

8農U

3
1

G．乙positivecases

Positivity

Station

1986

−

No．of

of examinees，No．examined for G，彪吻わ1協α（0．乙）and No．of O．ム

rate （％）

2．検出成績

19

4

8

4

9．3

2．7

7．5

5．8

6

59

19．4

8．5

低率であった。

検査の結果，692名の8．5％にあたる59名から，ランブル鞭毛虫の嚢子あるいは栄養体を検出した。

3．陽性者の旅行期間

59名のランブル鞭毛虫陽性者の旅行期間の内訳

各年の陽性者数と陽性率は，1986年は132名中18は，11−14日が6名，15−29日までが26名，30日

名（陽性率13．6％），1987年は205名中19名

以上が27名となり，2週間以上の者が53名と全体（9．3％），1988年は148名中4名（2．7％），1989年の89．8％を占めた。各年の旅行期間毎の陽性者数は107名中8名（7．5％），1990年は69名中4名を表3に示した。

（5．8％），そして1991年には31名中6名（19．4％）

4．対象者および陽性者の旅行先であった（表1）。全期間を通しての，各月ごとの検査対象者の中には，インド，ネパール以外に合計の陽性率を表2に示したが，3月（9．2％），

経由国あるいは滞在地として，タイ，香港，シン

4月（13．6％），5月（13．6％），9月

ガポール，中国などの諸地域へも旅行した者が（11．3％），10月（14．8％）の春季，秋季に高率で37％あり，その滞在期間も長短さまざまであった。

あった。これに対して1月には1．8％，また7月，

そこで，他地域への旅行の有無は今回考慮外とし，12月には全く検出されないなど，夏季，冬季には対象者をインド旅行者（インドおよびインドと他地域への旅行者），同様にネパール旅行者およびイ

Table2

Seasonal
rate

ofvariationin positivity

G．勉窺わ1ゑ z infection

in1986−

1991

Month

Apr．

Jul．

Aug．
Sep．
Oct．

Nov．
Dec．

Total

692

59

となり，ネパール旅行者群の3．2％（2／62）よりrate（％）
1．8

7．7

Table3

13．6

Year

6．7

1986

0

1987

6．1

1988

11．3

1989

14．8

1990

8．8

1991

0
8．5

of

overseatravelofG．彪郷6・

1勿positive Cases

9．2

13．6

Days

No．of

Days

Positive

Tota1
（％）

11−14

59

oftravel
15−29

1

30≦

1910り乙QJ

Jun．

Positivety

ΩU
94QU46
1
1

May

forG．励伽positivecaseS

1⊥−

Mar．

G，伽吻ゐ枷

14716106643

Feb．

毎の検査対象者と陽性者を集計した。その結果，インド旅行者群における陽性率は8．4％（35／419）

No．of

2
51 5 8374
55
1 884129523

Jan．

No．examined

ンド，ネパール両国旅行者の3群に区分し，各群

6

26

27

（10．2）（44．1）（45．7）

293

Table4

Desination
for G．」

the

cases

examinedz〃め」毎andofG．如

z配彪posi・

Table5

Age

and

cases

sex

with

tive cases

India十Nepa1

211
other

for

Female

3．2

2

areas

4

Male

8．4

10．4

3

30−

40−

50一

3

3

1

49

7り乙

62

20−

41

Nepal

10−

09

419

0−9

the

Total

Se丈

No．of
（％〉
positive
5
り乙2
0D

India

＊Including

of

Age

No．of
examined

Destination幸distributibn

G．め吻ゐ磁

Total

0

59

Table6

Results of bacteriological examina−

example Thailand，

Hongkong，China etc．

tion

in59cases

with G、如解6枷高率であった。またインド，ネパール旅行者群のPathogen陽性率は10．4％（22／211）と最も高かった（表4）。

isolated串Total

SHI十SALSHI十Cj

SHI

SAL

ETEC

3

1

11

2

1

5．陽性者の年齢および性別陽性者の平均年齢は25．2歳で，その内訳は20歳

17＊SHl：S物憩8」毎SPP．

SAL：Salmonella

代が49名（83％），10，30，40歳代が各3名，50歳

spp．

Cj：C伽ρ吻δπ6孟oγ勿観f

代が1名であった。また男女比では，男性が47名

ETEC：Enterotoxigenic Esoんε■foh池ooJと全体の79．7％を占めていた（表5）。

6．病原細菌との重複感染例
多く，重複感染例の70％以上を占めていた（表ランブル鞭毛虫の他に，1種類以上の病原細菌が検出された者が，陽性者の28．8％（17名）に見6）。

られた。このうちでは赤痢菌感染者が15名と最もTable7 Clinical sings

Clinical

cases

No．of

No，of
multiple

18

cases
59

（77．8％）

43（72．9％）（22．2％〉

16（27．1％）

・Fever

1

1

pain

and

Total

cases

15（36．6％）

fever

08

pain

・Abdominal

Total
infection†

6︻﹂

with

・Abdominal

G彪吻δ伽

44

No．of
29（70．7％）
12（29．3％）

diarrhoea

Loose passage

25（42．4銘）

10（55．6％）

20・Fever1

1

Diarrhaea

3 （7．3％）Loos姶passage
Cured

34（82．9％）1⊥直U1⊥and vomiting
・Abdominal pain，
fever and vomiting

（at

with

41

（ononset）

Combinedthesingleinfection‡

signs

Wateryin2quarantine）†Multiple

1＊Single infection：Cases

4 （9．8％）infected

infection：Cases

withinfected（5．6％）（88．9％）（5．6％）

4（6．8％）

50（84．7％）
5（8．5％）

G彪解ゐ1勿only。

withG彪励磁andotherpathogen（s）．

2947．陽性者の臨床症状28例）となっている。これらの報告における調査

ランブル鞭毛虫陽性者の発病時，および検疫時

対象者は一般入院・外来患者や人間ドック入院患の症状をまとめたものが表7である。一日数回か者であり，著者等が対象とした下痢症患者とは異ら数十回の水様性下痢をもって発病した者が最もなることから，これらの成績をそのまま今回の陽多く43名（72．9％），ついで一日数回の軟便が16名

性率と比較することは難しい。しかし両成績間に（27．1％）であった。また水様性下痢あるいは軟大差が認められることは，インド，ネパール長期便に，腹痛，嘔吐，発熱のいずれかの症状を単独旅行者が，ランブル鞭毛虫感染のハイリスクグに，または複数の症状を伴い発症していた者が25ループとなり得ることを改めて示唆する結果と名（42．4％）を占めていた。発病時の症状では，なった。

腹痛や発熱を伴っていた者の割合が，ランブル鞭

ランブル鞭毛虫の推定感染国としてインド，ネ

毛虫単一感染者の36．6％と比較して，細菌との重パールが重要であることは，前報（木村ら，1987）

複感染者においては55．6％と高率であった。またおよび金（1988）の報告によっても指摘されてい検疫時における臨床症状では，軟便が継続している。今回の旅行先群別での集計では，インド旅行た者が50名と全体の84．7％を占めていた。また検者群とインド，ネパール両国旅行者群での陽性率

疫時すでに症状が回復していた者は，単一感染者（8．4％および10．4％）が，ネパール旅行君緒でのに多く見られた。

陽性率（3．2％）と比較し高率であった。これは推定感染国として，インドがネパールと比較してよ考察り重要であることを推測しうる成績であると考えられる（表4）。

今回の調査で問題となる点として，年々のラン

今回の調査でも，20歳代青年が陽性者の83％をブル鞭毛虫検査対象者数の減少が挙げられる。特占め（表5），また各年とも陽性者の80％から90％に1990年以降の検査対象者数の低下は著しく，が2週問以上の旅行期間を有していた（表3）。こ

1991年では1986年の1／4以下となっている（表の結果は，トレッキングやボランティア活動でこ1）。この期間中，大阪空港における総検便数にはの地域に長期滞在することが，腸管寄生原虫や蠕大きな変動がないことから，インド亜大陸への長虫感染の機会を増大させることをさらに裏付ける

期旅行者の減少が，低下の直接の原因と考えられものとなった。

る。この点の詳細は明らかにしえなかったが，こ陽性率の季節的変動については，前報では春季の期間はインド，ネパール両国間の緊張や，インおよび夏期に高かったが，今回は春季および秋季

ド国内情勢の不安などがあり，これが長期旅行者に高率であった（表2）。いずれも休暇中，あるい

減少に少なからず影響があったものと推測される。

は休暇明けの帰国者が増加する時期であり，この前回，著者等が実施した海外旅行者下痢症患者

時期の旅行者下痢症患者には，充分に注意を払うの腸管原虫調査では（木村ら，1987），下痢症患者

必要があろう。

の中で，特にインド，ネパール長期旅行者からの陽性者の28．8％にあたる17％からは，赤痢菌そ

ランブル鞭毛虫陽性率が14％に達した。今回の調の他の下痢起因性細菌が同時に検出された（表査では，陽性率に実施年により2．7％から19．4％6）。これら病原細菌重複感染者の発症時の臨床症と大きな差が見られたが，全期問を通じては8．5％状では，ランブル鞭毛虫単一感染者より，発熱やであった（表1）。国内各地の総合病院におけるラ

腹痛，嘔吐を伴うケースの割合が多く見られ（表ンブル鞭毛虫感染状況については，鈴木（1982），

7），病原細菌の影響を推測させるものであった。

角ら（1986），関戸ら（1988）および市澤ら（1990）

しかし，発症時およびその後の継続的な水様下痢が報告しており，その陽性率はそれぞれ，0．56％

や軟便を示す下痢症患者には，病原細菌検出の有（9，473件中53例），0．33％（14，756件中49例），

無に関わらず，ランブル鞭毛虫感染を疑い，検査

0．16％（6，168件中10例）および0．6％（4，363件中を実施する必要があると思われる。またランブル

295

鞭毛虫陽性者からは，胆嚢炎や肝炎様の激しい症見られた。陽性率の最も高い年は1991年で状の者は見られなかった。しかし，本原虫の小腸19．8％，最も低い年は1988年で2．7％であった。ま

上部のみならず，胆道内への寄生例も報告されてた春季，秋季には，夏期，冬期と比較して陽『生者いることから（金子ら，1979；津嶋ら，1985；山が高率に見られた。

田ら，1980；奥野ら，1976），今後帰国者の中にも

2）ランブル鞭毛虫陽性者59名のうち，2週間以胆嚢炎等の症状を呈する感染者も見いだされる可上の長期旅行者が53名（89．8％）を占めていた。

能性がある。

海外，特に熱帯地域発展途上国への旅行者は

3）旅行先別による検討では，インド，ネパール
両国ぺの旅行者群中の陽性率が10．4％と最も高年々増加の傾向にあり，それとともにランブル鞭

く，ついでインド旅行者群の8．4％，ネパール旅行

毛虫症の国内への持ち込みの増加も懸念される。

者群の3．2％であった。

このような状況のもと，今後は腸管細菌のみなら4）陽性者の平均年齢は25．2歳，男女比は8：2

ず，ランブル鞭毛虫を始めとする腸管寄生性原虫であった。また陽性者の68％が20歳代の男性でや蠕虫に対しても，検疫体制を強化，拡大すべきあった。

5）陽性者の28．8％にランブル鞭毛虫の他に，赤ではないかと考える。

痢菌を始めとする他の病原細菌が検出された。

結6）陽性者の臨床症状の特徴として，発病時に頻語回の水様性下痢と，以後の軟便の継続が見られた。

インド・ネパール長期旅行者のランブル鞭毛虫
感染状況の解析を目的として，大阪空港検疫所か謝ら入国した海外旅行者下痢症患者について，1986
年より1991年まで6年間の継続した調査を行い，

辞今回の調査に多大なる御協力を頂いた，大阪空
港検疫所関係の方々に深謝いたします。

以下の成績を得た。

1）インド・ネパール長期旅行の下痢症患者692名

本論文の成績の一部は，第31回日本熱帯医学会中の59名（陽性率8．5％）にランブル鞭毛虫感染が総会（1989年11月，名古屋）において発表した。

文献1〉阿部久夫，神田輝雄，柳井慶明，橋本 智，小川良治，宮田義人，神保真澄，原田七寛，塚本定三，
木下善雄，有田美知子，竹田美文，三輪谷俊夫（1981）：海外旅行者下痢症の細菌学的研究（1〉昭和54年大阪空港における旅行者下痢症患者からの原因菌検査成績について，感染症誌．，55，679−690
2）市澤知子，加藤裕美，持塚いずみ，栗田雅史，瀬野尾一孝，鈴木了司（1990）：静岡県藤枝市地域に発生したランブル鞭毛虫症，日熱医会誌．，18，333−339
3）奥野哲二，小田義英，村岡松生，石井公道，土屋雅春（1976）：ランブル鞭毛虫症，日本医事新報，
2734， 27−30

4）金子清俊，角坂照貴，寺沢利昭，矢野孝，高雄哲郎（1979）：ランブル鞭毛虫による胆嚢炎の1症

例，愛知医大誌．，7，257−262
5）木村明生，峯川好一，北浦敏行，中野宏秋，後藤郁夫，池田長繁，阿部久夫，小野忠相，中林敏夫（1987）：海外旅行者下痢症患者における腸管原虫検出について，感染症誌．，61，789−796
6）金龍起（1989）：都市立伝染病院に収容された輸入感染症腸炎の起炎菌と臨床，日本臨床，47，
28−327）宮田義人，田口真澄，大村寛造，吉田昭夫，南 明宏，鈴木則彦，高井慎也，楠井善久（1991）：大
阪府における輸入感染症に関する調査報告一平成2年一，大阪府公衆衛生研究所所報，公衆衛生編，

2，91−198）鈴木禾甫（1982）：一病院で発見された寄生虫症について，一特にMGL法にタる検便成績など一，

296

日本医事新報，3053，43−46
9）角 佳代子，中 甫，清瀬 闊，杉山悦朗，篠永 哲（1986）：首都圏住民の腸管寄生虫感染状況に関する一考察，感染症誌．，60，1317−1323
10）関戸定彦，須賀真由美，山崎賢一郎，足立京子（1988）：当院における過去5年間の寄生虫検出状
況，第20回埼玉県臨床衛生検査学会抄録集，114
11）津嶋恵輔，三上勝也，村上哲之，杉山雄一，土田 博，山形尚正，笹村雅人，三上賛麿（1985）：ラ
ンブル鞭毛虫による胆道感染の2例，医療，39，452−455
12）山田澄夫，津野正肚，太田健爾，松下 秀，工藤泰夫，坂井千三，大橋 誠（1983）：東京都における輸入腸管感染性腸炎の細菌学的検討（1982年），感染症誌．，57（臨時増刊号），136
13）山田千尋，李 慶鯨，島崎千尋，中西 忍，佐々木 享，中村喜久生，平野伸二，香月昭人，伊地し知浜夫，山田 稔，猪飼 剛，吉田幸雄，貝増勲彦，日野良俊，久我正巳（1980）：不明熱の原因としてのG∫伽4∫α砺窺わ伽胆道感染の1例，最新医学，35，855−858

297

SURVEY OF GIARDIA LAMBLIA INFECTION IN RETURNINGTRAVELERS WITH DIARRHOEA FROM INDIA AND NEPALAT OSAKA AIRPORT QUARANTlNE STATIONAKIO KIMURAl, YOSHIICHI MINEKAWA1, NAGASHIGE IKEDA2
KENJI SHIMOIRISA', YOSHIHISA KUSUl', YASUKAZU MATSUMOT0

AND TOSHIO NAKABAYASH16
Received September 14 1992/Accepted October 5 1992

Patients with traveler's diarrhoea who returned from traveling India and/or Nepal morethan 10 days were subjected to stool examination for Giardia lamblia at Osaka International

Air Port Quarantine Station in 1986 to 1991. Results obtained were summarized as follows:

1 ) G. Iamblia was detected in 59 of 692 cases examined (positivity rate, 8.7%). The
positivity rate in each year was: 13.6% in 1986, 9.3% in 1987, 2.7% in 1988, 7.5% in 1989,

5.8% in 1990 and 19.4% in 1991, respectively. The seasonal variation in the piositivity

rate was recoguized as it was higher in March (9.2%), April and May (13.6% each) ,September (11.3%), and October (14 .8%) than other months. No positive case wasfound in July and December.
2 ) 89.8% of the positive cases were the travellers over 14 days.
3 ) Travellers who visited both India and Nepal showed high positivity rate (10.4%) . Those

who visited only India or Nepal showed lower rate (8.'4% and 3.2%, respectively) .

4 ) More than 68% of positive cases were male at the age of 20s.
5 ) In 28.8% of the positive cases, some species of pathogenic bacteria (e,g. Shigella spp.)

were concomitantely detected.
6 ) Major complaints of the positive cases were watery diarrhoea, Iastig and loose passage.
It was pointed out from the results that stool examination for G. Iamblia to returning
travelers with dearrhoea from India and Nepal should be made at qurantine as they wereat high risk of G. Iamblia infection.

Department of Virology, Osaka Prefectural Institute of Public Health
2

3
4
5

6

Osaka Quarantine Station
Nagoya Qurantine Station
Nagasaki Qurantine Station
Osaka Airport Qurantine Station
Department of Parasitology, Fujita Health University School of Medicine

日熱医会誌，第20巻

第4号

1992年

299−303頁

299

症例報告

ハロファントリンにより治癒した
輸入三日熱マラリアの1例
淀縄

聡1・3・狩野 繁之2・＊・斎藤

横山 雄次3・川合

覚2・鈴木

達也3・

守2

平成4年9月3日受付／平成4年10月12日受理

はじめに

嘔気，下痢を認め，急性胃腸炎の疑いで入院となった。

1991年の日本人年間海外渡航者数は入院時現症：体温40．3。C，脈拍102／分整，血圧

10，633，777人，また外国人の日本への入国者数は120／60。結膜に黄疸，貧血を認めず，胸部聴診所

3，855，952人であり（法務省入国管理局統計），そ

見に異常はなかった。下腹部に圧痛を認めたが，の数は年々増加し，それに伴って日本国内におけ

筋性防御反応は無かった。腹部聴診上，腸蠕動のる輸入マラリアの症例数も増えてきている。現在

充進を認めた。腹部超音波検査では，肝脾腫を認

年間罹感者数は，届け出られるだけでも100名を越めなかった。

え，マラリアはもはやめずらしい病気ではなく入院時検査成績：CRPが陽性を示したが，白血球なってきている。しかし，日本国内で入手可能な増加は認めず，また貧血も無かった（図1）。生化

抗マラリア薬は限られており，有効かつ安全な治学検査では，軽度低K血症以外ほぽ異常を認めな療薬の導入に特別な関心が払われてしかるべきでかった。

ある。我々は，輸入三日熱マラリアを経験し，治入院後経過：上記所見よりウイルス性の腸炎が疑療薬としてハルファン（HALFANTM：

われ，入院後直ちに抗生物質の投与ならびに，発halofantrinehydrochloride）を試みた。ハルファ

熱，嘔吐，下痢による脱水・低カリウムのため補ンは1984年に臨床治験が開始され現在に至るが，液を開始した。しかし治療に抵抗して，体温は4

本邦においては薬剤の入手が困難である事もあっ

月15日より1日おきに39−40。Cの発熱を認めたて，これまでに治療報告はない。

（図1）。4月23日，血液培養検査を行ったが菌は検出されなかった。熱型より三日熱マラリアが疑症

例われたため，4月24日採取した薄層塗抹標本を調べたところ，赤血球内に三日熱マラリア原虫が認患者：39歳，パキスタン人男性。1989年5月よりめられた。寄生赤血球率は0．05％であった（写真

日本に滞在。

1，図1）。また，間接蛍光抗体法による三日熱マ

主訴：発熱，悪寒戦藻，嘔気。

ラリア原虫抗原，熱帯熱マラリア原虫抗原に対す

既往歴：1984年にパキスタンにおいてマラリアる抗体価は，それぞれ1：1，024，1：256であり，の既往がある。

血清学的にも三日熱マラリアと診断された。治療

現病歴：1991年4月初旬より発熱を繰り返し，4には，新しい抗マラリア薬であるハルファンを用

月15日堀江病院を受診した。受診時，悪寒戦慎，いた。ハルファン（1錠中ハロファントリン塩基

群馬大学医学部第一内科学教室（〒371前橋市昭和町3−39−22）
群馬大学医学部寄生虫学教室（＊別冊請求先：前橋市昭和町3−39−22）
堀江病院内科（太田市高林1800）

300

Date Apr唱1617酬9202篭222a2亀2526272B2930MFy↑herapy桝alfa醍5藤mgx3Primaqui離1騒m鯛輪y畠
マ▼▽
0，2％Parasitemia

蒋，1

Body「晦mperatwe

o

（燈C）

4薯
40
39
3a
3了
器

舘α唱獄
Ht

l％1

鼎、t綴ll462

401415356

1妨

12，3

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40
鳩00

36
3560
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20 糖

Figur母l Cli礁ica至course

Photo、1Giemsa−sta．ined

b圭ood

s瓢e獄r

ozoite声b）a9段n窪（｝tocy亡e

of

of

t赴e

，1

th曾patient．

patie鷺tshowi負暮a）寂trof｝h・oずP霧硲郷04 銘蜘擁∂鶴圭箪e庶1arged eryth画

rocytes、233mg）は，4月26日18100，27日0：00，6100

り，その後再発を認めていない。

に2錠ずつ合計6錠経口投与し，薬剤投与直前に，
耳朶血にて塗抹標本を作成した。また，4月28日
より肝内型の抗マラリア薬であるプリマキンを1

考察錠（蔦mg）ずつi4日間，毎朝一回経口投与した。

現在，本邦において市販されている抗マラリアハルファン投与後の体温は4月27日15：GOに薬は，F＆蹴sidar覗だけである。血漿中最高濃度も36，9℃の平熱に回腹した。また，寄生赤血球率も2−6時間で得られ，クロロキン耐性熱帯熱マラ

徐々に低下し，28日には，0．㎝％以下となった（図リアにも有効であるなど，一般輸入例の治療には1）。4月27日9：00頃に，ハルファンの副作用と適しているものと考えられる。しかし，消化器症

思われる嘔気嘔吐が軽度認められた渉，それ以状を始めとする副作用と，1，000人に1人程度に外の症状は認められなかった。4月3G日退院とな

重篤な皮膚・粘膜症状が報告されており，その点

301

において投与時に注意を要する（WHO，1990）。

期はおよそ1−2日と比較的短い（S．K．and

F．

また，Fansidar耐性熱帯熱マラリアの流行も既

Lab．Ltd．，1988）。Boudreauら （1988）は，ハに拡散しつつあり（WHOexpertcommitteeon

ルファン治療による平均解熱時間は60時間，平均

malaria，1992），新しい抗マラリア剤の開発が常原虫消失時間76時間と報告している。またChit・に必要となる。比較的新しい治療薬として，最近

chang

日本において著者らにより試された薬にラリア例のハルファン治療による平均解熱時間はmefloquineとartemetherがある。前者はキノリ
ンメタノールで構造上キニーネに似ており，特に42時間，平均原虫消失時間62時間と報告している。

andWongteptien（1989）は，三日熱マ

本例では前者が21時間，後者は確定できなかった

多剤耐性マラリアに有効と考えられているが38時間後に0．01％以下となり，治療において著（WHO，1990）。嘔気・嘔吐，平衡感覚障害を始効を示したと考えられた。経時的に原虫形態を観めとする副作用が問題となっているが，我々の経察したところ，4月27日6：00，即ち3回目のハ験では，軽い消化器症状を呈した以外副作用は認

ルファン投与時に，既に三日熱マラリア原虫の細めていない（大西ら，1991；Yamaguchi召∫認，

胞質はアメーバ状を呈さずむしろ濃縮傾向にあり，

1992）。後者は重症熱帯熱マラリアの治療に特に有28日8：00には空胞の形成が顕著であった。ハル

効で，副作用も軽微と考えられている。本邦におファンの副作用は表1に示すように下痢，腹痛，

ける治療例では，ほとんど手後れに近い重症マラ

嘔気，嘔吐等の消化器症状を中心に上げられるが，リアもすみやかな治癒に至り，副作用も特に認め頻度としては特に低く，安全に投与できる薬剤でていない（狩野ら，1988）。しかし再燃の高いことにより，一般輸入例に対する治療適応は無いと考Table l Clinical events after

える。

with

本報告で使用したハルファンは，特に薬剤耐性
マラリアに抗する治療薬として開発され，1984年

Clinicaltreatment

Halfan車
Post−treatment

eventseventsNumber（％）に臨床治験が開始された。治験報告例はすでにDiarrhoea69（6．8）1，000例を越え，治癒率は95％以上である（Smith

Cough64（6．3）

Kline

Abdominal pain

57（5．6）

Nausea39（3．8）

Vomiting

39（3．8）Dizziness

31（3．0）］日【eadache23（2．3）Fever

22（2．2）

Pruritus21（2．1）Chills20（2．0）

Backache18（1．8）Myalgia17（1．7）

Pallor14（1．4）

Palpitations

14（1．4）and French

Laboratories

Limited，

1988）。構造は図2に示すようなフェナントレンメ
タノールで，従来の抗マラリア薬と構造を異にし，その差異がマラリア原虫のハルファンに対する交差耐性の低いひとつの理由と考えられている。血
中最高濃度は一回量投与後6時間で得られ，半減HO＼
CH

CH2CH2N［（CH2）3CH3］2

−

CI

1
ク

＼

グ＼

Jaundice＊The

F3C
Figure2Structure ofCI
halofantrine．

ed8（0．8）

study involved975naturally
subjects

and36

artificially

volmteers（Source：Smith
FrenchLaboratories

infect・
infected

Kline

Limited）．

and

302

今後注目されるべき抗マラリア薬と考えられる。

あると考えられている。本症例における軽度の嘔気・嘔吐は薬剤投与前からも認められていたが，ハルファンによる副作用とも考えられた。

おわりに

本症例は日本滞在後およそ11カ月で発症した，

一日おきの熱型とそれに伴う症状を示す典型的な

パキスタン人の三日熱マラリアの再発例を経験

三日熱マラリアの再発例と考えられた。三日熱マし，その治療薬としてハルファンを試み著効を示

ラリア治療薬としてはクロロキンが妥当で，現在した。またハルファン投与後の患者副作用は，軽のところハルファンは第一選択薬とは考えられな微であった。輸入マラリアの例数も増えるにつれ，いが，本邦においては，これまでにハルファンに

クロロキン耐性マラリアに遭遇する機会も多くな

よる治療の報告例はなく，その有効性をまず例証，ると考えられるので，その新しい治療薬として，報告するための治験として，患者に説明をし同意

今後ハルファンの適用例を検討して行く必要があを得た後に治療を行った。臨床諸家が抗マラリアろう。

薬を選択する時，その薬剤による速やかな原虫消本症例の要旨は第33回日本熱帯医学会総会（平失効果を特に期待する。我々はさらに多剤耐性マ

成3年11月，京都）で発表した。

ラリアを含む熱帯熱マラリア数例を，同様にハルファンで治療しているが（投稿準備中），原虫消失

時間など，治療効果においてハルファンは従来の謝

抗マラリア薬に匹敵していると考える。現在本邦

辞

本報告の作成にあたり，鈴木幹雄医師に助言をにおいて，熱帯熱マラリアによる重症例や薬剤耐いただいたことを付記する。

性マラリア症例が増えてきており，ハルファンは献文1）Boudreau，E．F．，Pang，L．W．，Dixon，K．E．，Webster，H．K．，Pavanand，K．，Tosingha，L，Somutsa．

kom，P．andin

Can丘eld，C．J．（1988）：Malaria：treatment

initial neldtrialsemcacyofhalofantrine（WR171，669）

in Thailand，Bull．WHO．，66（2），227−235

2）Chitchang，S．andWongteptien，S．（1989）：Aclinicaltrialofhalofantrineinacutemcomplicat−
ed malaria in Thai soldiers，HALOFANTRINE in the treatment of multidrug−resistantmalaria，Parasitology Today，21−26，Elsevier Publications，UK

3）狩野繁之，辻正周，細谷純一郎，鈴木守（1988）：重症マラリアのQINGHAOSUによる治療

例，日熱医会誌．，16（4），301−307
4）大西健児，柴田雅彦，村田美紗子，狩野繁之，鈴木守（1991）：メフロキンで治療した熱帯熱マラリアの1例，Clin．ParasitoL，2（1），33−34
5）Smith Kline and French Laboratories Limited（1988）：Halfan Product Data，UK
6）WHO（1990）：Severe and complicated malaria，Trans．Roy．Soc．Trop．Med．Hyg．，84（SuppL2），25−33
7）WHO expert committee on malaria（1992）：Nineteenth Report，88）Yamaguchi，T．，Ajisawa，A．，Negishi，M．，Masuda，G，Kano，S．and Suzuki M．（1992）：Four
cases

of

malaria successfully

treatedwithmenoquine，Jpn．J．Trop。Med．Hyg．，20（1），71

303

AN IMPORTED CASE OF VIVAX MALARIA TREATED

WITH HALOFANTRlNE
SATOSHI YODONAWAl' 3, SHIGEYUKI KANO', TATSUYA SAIT03,

YUJI YOKOYAMA3, SATORU KAwA12 AND MAMORU SUZUK12
Received September 3 1992/Accepted October 12 1992

[Case] The patient was a Pakistani male, 26 years of age, who came to Japan in May,
1989. The last malaria episode was in Pakistan about 5 years prior to this date. On admissionto Horie Hospital on April 15, 1992, he had a body temperature of 40.3'C, which did not
respond to antibiotics. Vivax malaria parasites were first detected from thin blood smears
taken on the 24th at the density of 0.05%. Antibody titers against Pkrsmodium vivax andPlasmodium falciparum antigens were shown at 1:1.024 and 1:256 respectively by the indirect
fluorescent antibody test. Two tablets each of Halfan (halofantrine hydrochloride, 233 mg
base/tablet, Smith Kline and French Laboratories Limited) were administered orally at 18:OO
on 26th, O:OO and 6:OO on 27th, followed by primaquine at 15 mg per day for 14 days. Body
temperature fell to normal at 15:OO on the 27th (36.9'O and parasites were reduced to below
O:O1% parasitemia on the 28th. No adverse reactions were recognized except slight nausea

and vomiting.
Halfan has been used for the treatment of human malaria since 1984, and reported to bea effective against all parasite species. The drug is a phenanthrene derivative which does not
slpare chemical structure with any other antimalarials, and is thefefore particularly effectivein the treatment of drug resistant malaria. Our report is the first in Japan of successfultreatment of inalaria with Halfan. Clinical side effects df the drug on this patient seem tohave been very mild. Parasite clearance was rapid and fever dropped dramatically. Fansidar
is the only antimalarial drug available in Japan so far, and imported drug‑resistant malaria

not only against chloroquine but Fansidar has been on the increase. The general use of
Halfan is thus expected.

1 Department of Internal Medicine and2 Department of Parasitology, Gunma University School of Medicine (3‑39‑22 Showa‑machi,
371 Maebashi, Japan)
3 Horie Hospital (1800 Takabayashi, Ota, Gunma)日熱医会誌，第20巻 第4号

1992年 305−312頁

305

症例報告

熱帯熱，三日熱マラリア混合重症感染の1例
一artemetherによる治療経験一

穂坂

茂1・＊・石川、章1・細野孝郎1・飯国弥生1・

近革 啓文1・小林豊1・中村
健2・伊藤 洋一2・
大友 弘士3・狩野 繁之4・鈴木守4
平成4年9月10日受付／平成4年10月14日受理

緒言ではクロロキンの週一回の予防内服を行っていた。

4月25日帰国。5月2日，38。Cの発熱が出現。軽熱帯熱，三日熱マラリア混合重症感染の1例を度の悪寒戦懐を伴った。4日近医を受診し，風邪報告する。患者は31歳男性。インドネシアより帰といわれ投薬を受けたが，症状の改善はなく，39−

国後，発熱と下痢を来し，発病7日目に本院入院。 4伊C台の発熱が持続した。7日より1日5行以上
脳症，急性腎不全，ショックとDICを合併し，熱帯 に及ぶ水様性下痢を認めた。8日北里大学病院内
熱マラリア原虫寄生赤血球率は最高29％に達した。

科を受診。受診時血圧低下と黄疸が認められ緊急

種々の抗マラリア剤を投与したが臨床症状は急速入院となった。

に進行し，腎不全は血液透析を必要とした。最終

入院時現症：身長165cm，体重60kg，体温

的にartemetherによる治療が奏功し救命し得た。

4ぴC，血圧80／60mmHg脈拍数80／分・整。意識また，腎生検で急性尿細管壊死を示唆する所見を清明。皮膚：四肢末梢は湿潤で冷感あり。躯幹に得た。

虫刺され様の丘疹が散在。出血傾向はなし。眼球本邦における，重症マラリア治療の貴重な症例と考え報告する。

結膜に黄疸を認めた。眼瞼結膜に貧血はなし。リンパ節：角蜘せず。胸部：異常所見なし。腹部：心窩部から右季肋部に圧痛と反跳痛を認めた。心症
患例

者：31歳，男性。会社員。

主訴：発熱，全身倦怠感，下痢。

窩部に肝を3横擶蜘した。脾臓は触れなかったが，トラウベ半月の縮小を認めた。下肢に浮腫なし。神経学的に異常所見なし。

入院時検査成績（表1）：検尿で蛋白尿と沈渣に既往歴：特記すべきことなし。

白血球，赤血球，穎粒円柱を認めた。便潜血が陽

家族歴：特記すべきことなし。

性であった。末梢血では白血球，赤血球ともに増現病歴：1991年4月17日から25日まで，実験動加していたが，高度の血小板数減少，aPTTの延物の調査目的でインドネシアのジャワ島南西海岸

長とFDPの増加を認めた。血沈は1時間値3mmに位置するMuarabinuavgeおよび同所から約50であった。血液生化学検査では溶血と腎機能障害

km離れたDeli島に合わせて3日間滞在した。現地の所見が認められた。総コレステロールが低値で北里大学医学部内科（＊別冊請求先：〒228相模原市北里1−15−1）
北里大学医学部寄生虫学教室
岐阜大学医学部寄生虫学教室
群馬大学医学部寄生虫学教室

306
Table lLaboratory

findings

gravityLprotein

（3十）

blood

（2十）

O34

TP

6．19／dJ

CRP

Alb

54．5％

RA

α1−91b

7．2

FANA

9．2

Anti−ENA

10．8

Anti−DNA Ab

γ一glb

18．3

CA噛

T．Bir

3．O mg／dJ

Anti−cardiolipin

D．Bil

1．8

CH50
C3

16U／mJ
42mg／dJ

C41C綿

101．2μg／mJ

RBC，WBC

5−8／HPF

α2−glbgranUlar

（十）

β一91b

CaSt

NAG

78．4U／J

Stoo1：

occult blood

Peripheral

Immunology：

Chemistry：

Urinalysis：（2十）801U／」

GOT
GPT
ALP

blood：

WBC

12，000／mm3

myelo

LO％

meta

8．O

γ一GPT

43．O

LDH
CPK

stab

seg

35．O

eosinoO．0

1ympho
mono

4．O
2．O

baso
atypical

lym

RBC

TG

BUN

14U／mJ
（＋）

Ab

（十）

IgG

1，200mg／dJ

IgA
1gM

249
338

Coomb

s

test

（一）

STS

（＋）

TPHA

（一）

Creatinine

UA

8．0

PH

7．42

Na

136mEq／J

K

4．9

PCO2
PO2

3L3Torr
95．7

Cl

95

HCO3

20．7mEq／J

46mg／dJ

BE

−1．9

14

SO2

1．3×104／mm3

PT

12．1（11．5）sec

aPTT

57．0（32．6）

Fibrinogen

205．9mg／dJ

ESR
FDP

80＜160μg／m1

Serum

Hb．

］E【aptoglobin

BGA：

97．5％

3mm／hrATIII
Plasminogen70％＊CA：circulating

anticoagulant

榊IC：immme

T．cho

（十）

O．O

49．2％

Plt

44
90mg／d1
387
42

20x
Ab，

7．O
17．29／dl

Ht

1，592

（一）

3．プ

508×104／mm3

Hb

55
182
54

26，900μg／dJ
test

49
complexあった。免疫学的検査ではCRPの高値と血清補体（図2B）。熱帯熱マラリア原虫寄生赤血球率は価の低値を認めた。免疫複合体は陰性であった。

12％で，三日熱マラリア原虫寄生赤血球率は0．7％

血清梅毒反応は生物学的偽陽駐を示し，循環抗凝であった。以上より三日熱，熱帯熱マラリア混合

血素が陽性であった，腹部超音波検査では，肝脾

感染で急性腎不全とDICを示す重症マラリアと診腫を認めた。

断した。直ちに塩酸キニーネ600mg経口投与とド入院後経過（図1）：入院時直ちに末梢血薄層塗

キシサイクリン100mg滴静注を開始，計2回投与

抹標本を検鏡したところ，膨大し，シュフナー斑

した。十分な補液，昇圧剤およびFOYとハプトグ点を有する典型的な三日熱マラリア原虫寄生赤血

ロビン製剤も併用した。しかし9日に熱帯熱マラ

球と，熱帯熱マラリア原虫の輪状体をもち，大きリア原虫寄生赤血球率は29％に達した。高熱が持さは正常で斑点のない赤血球が認められ（図2

続し，下痢が頻回であった。塩酸キニーネを250A），その後の標本からは生殖母体も認められたmg点滴静注に変更し，ファンシメフ1錠を投与し

307

10

1991May 8
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Figure lSummary of thepatients

hospita1，UV：urine

clinicalcourse．

ADM：admission

volume，BT： body

to

our

temperature，HD：

h6modialysis，P．f．： 」P嬬 zo4伽 ￠血Joゆon冨解，P．v．≡P伽卿04伽吻吻砒．

たが経口薬は消化器症状のため継続は困難であっアランスは105．11／dayであった。6月1日よりプた。9日の深夜から無尿に陥った。ζちらからのリマキン15mg／dayを2週間投与した。7月18日

質問に対する応答が乏しくなり，意識レベルの低発熱出現。三日熱マラリアの再発を認め，クロロ

下を認めた。脳波では全誘導にかけてlow

キンとプリマキンを2クール投与にて改善した。

volt・

ageandslowwaveを呈し，汎性異常を認め，脳11月23日39℃の発熱が出現。再度三日熱マラリア

マラリアの合併が疑われた。10日より血液透析をの再発を来した。26日ハロファントリン投与後，導入し，抗マラリア剤をartemether（Kunming
China）にプリマキン15mgを2週間，引き続きクロロキン
300mgとプリマキン45mgを週1回，8週間投与変更した。投与量は初回に200mg，以後6時間毎したところ現在にいたるまで再発は認めていない。

に100mgずつ追加し，総量600mgを筋肉内注射し腎生検所見（図3）：光顕レベルでは糸球体はほた。原虫寄生率は急激に低下し，12日には原虫のぼ正常で，尿細管の中等度萎縮と間質へのび漫性消失を確認した。発熱，下痢も消失し，意識清明の炎症細胞，好酸球の浸潤を認めた。間質，尿細となり全身状態は速やかに回復した。Artemeth−管の変化が主体で，急性尿細管壊死の再生像と考erによる治療後，再燃防止のためmenoquine500
mgを12日，13日に投与した。腎機能も回復，利尿えられた。

Phamlaceutical

Factory，Yunnan

血清マラリア抗体価（図4）：問接蛍光抗体法が得られ，17日には透析を離脱し得た。血小板数（IFAT）により測定した。5月10日に熱帯熱マラ

は16日には正常値に復した。22日経皮的腎生検をリア原虫抗原に対し256倍，三日熱マラリア原虫抗施行した。30日退院。退院時BUN

llmg／dl，原に対し1，024倍の高値を示した。その後，経時的

creatinine1．2mg／dJ，24時間クレアチニンクリに抗体価の測定を続けたところ，患者の回復に

308

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伴って下降する抗体価が，7月18臼，鉱月23日のて脳症，重度貧血，低血糖，出血傾向，DIC，黄2回の三日熱マラリアの再発毎に三日熱マラリア痕，腎不全，肺水腫，シ落ックなどが挙げられ，抗体価が熱帯熱のそれに比較して，有意に上昇し赤血球内原虫寄生率5％以上となっているていることが認められた。

（WHO，ig90）。本症例は入院時発熱，下痢，黄疸，ショック状態を呈し，急性腎不全とDIC，経過考

察

中に脳マラリアを合併した。熱帯熱マラリア原虫
寄生率は入院時12％，最高29％と高率で，極めて重症熱帯熱マラリアは，急速な進行を示し，致重症のマラリアといえる。本邦ではマラリアはほ死的合併症を引き起こすことから，早期診断と共とんどが輸入例として遭遇するため，医者の認識に適切な抗マラリア薬の選択が必須である。

が乏しく見逃されることも少なくない，本症例はWHOの重症マラリアの基準では，臨床症状とし

他医で風邪と診断され，本院への受診は発症7日

3a9

A)

B)

Figure 3 Renal‑biopsy specimen. A) Changes in the glomerulus and theproximal ttibules are minor. B) The interstitial tissue is infiltrated

by plasma cells and lymphocytes (Hematoxylin and eosin; x 100) .

titer
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P.f.: Plasmodi im falciparum, P.v.: Pla.sm(rdium vivax.

310目であった。熱帯熱マラリアは，発病後治療開始

くことが出来ない。ショック，DICに対する処置，

遅延日数が5日を過ぎると，生命の危険が高くな

適切な透析導入も今回救命し得た大きな要素であることが指摘されている（海老沢ら，1991）。熱帯る。原虫寄生赤血球の破壊によるヘモグロビン血熱マラリアではマラリアの古典的な症状とも言え症，ヘモグロビン尿症が腎不全の一因に挙げられる周期的な発熱は特徴的ではなく，多彩な症状をている。ハプトグロビン製剤の使用は，この病態呈する（Scully8∫41．，1989）。海外渡航者に発熱に対して有効かもしれない。

を見た際，マラリアを念頭におくことが強調され熱帯熱マラリアに伴う腎障害には急性腎不全と，る所以である。今後，重症マラリアに遭遇した場

稀ではあるが免疫学的機序を介する腎炎，ネフ合，よりよい対処をするべく，今回行った治療にローゼ症候群の2つが報告されている

あたっての問題と反省すべき点を挙げてみたい。

（Boonpucknaving

まず重症マラリアの治療は非経口的に行うことが腎不全は，高度の原虫血症と溶血を呈する症例に原則で，塩酸キニーネ点滴静注が第一選択とされ合併する。その腎組織所見に関しての報告では，とている（WHO，1990）。しかし，我々は注射薬

糸球体は保たれるが，尿細管の変性と萎縮，尿細の入手が間に合わず，塩酸キニーネの経口投与で管上皮細胞内および尿細管腔内の色素穎粒の存在開始せざるを得なかった。塩酸キニーネ点滴は第と，間質への小円形細胞浸潤，線維化といった尿andSitprija，1979）。急性

2病日より開始し得たが，寄生原虫率の上昇と臨

細管，間質の病変が主体とされ，いわゆる急性尿床症状の悪化を認め，キニーネの治療をそれ以上細管壊死の所見である（Agrawalθ∫α」．，1984；

継続することは危険であると判断された。

Stoneε∫α1．，1972）。本症例でも糸球体の形態はArtemetherは，中国において古くからマラリ

ほぽ正常に保たれていたが，尿細管，間質の変化

ア治療に用いられてきた、4吻卿臨α碗％襯よりがあり，いままでの報告にほぼ一致する所見で抽出されたqinghaosuの誘導体である。原虫消失あった。

時間，平均解熱時間共に極めて速効性で，耐『生マラリアに対する有効性，軽微な副作用，また非経おわりに口投与可能から重症マラリアに対する薬剤として注目されている（Klayman，1985；狩野ら，熱帯熱，三日熱マラリア混合感染で，急性腎不1988）。本症例1こおいてはArtemether投与1時間

全，溶血，DIC，ショック，脳症状を合併した重症

後には原虫の膨化，細胞質内の空胞形成などの変例を経験した。重症マラリアは，短時間で症状が化が見られ，2時間半後にはほとんどすべての原進行する。輸入マラリアの増加と共に，重症マラ虫の染色性に変化が起こり，細胞質濃縮に陥った

リアに遭遇する機会も多くなることが予測され，原虫も多数観察された。38時間後には末梢血中のその認識と迅速な対応のできる医療環境の整備が原虫は消失し，臨床症状も速やかに改善した。

望まれる。

Artemetherの速効性が，臨床所見と良く一致して確認できた。

本論文の要旨は第66回日本感染症学会総会，ならびに第3回臨床寄生虫研究会で発表した。

今回のような重症マラリアでは，補助療法も欠文1）Agrawal，S，M．，Kumar，L．and

Naidu，M．（1984）：Acutecase report，Indian J．Pediat．，51，109−1132）Boonpucknaving，V．and Sitprija，V．（1979）：Renal
infection

inman，Kidney

献
renal

diseasefailure

in

acute

in

falciparum

malaria−a

P伽解04彪吻血」6ゆσn槻Int．，16，44−52

3）海老沢 功，田辺清勝，小原博（1991）：熱帯熱マラリア治療における開始遅延の意義，日熱医会

311
E;b. , 19, 49‑56,

4 )i;!J. El fl

,

t

:i 1,

B]

4!‑

,

7i

F (1988)

l

77 IJ 7 )QUlNGHAOSUe*?

b‑"b., 16, 301‑307

5 ) Klayman, D.L. (1985): Qinghaosu (Artemisinin) ; An antintalarial drug from China, Science,
228, 1049‑1055

6 ) Scully, R.E., Mark. E.J., McNeely W.F. and McNeely, B.U. (1989): Case records of theM ssachusetts General Hdspital, Weekly clinicopathological exercises, New Engl. J. Med., 321,

597‑605
7 ) Stone, W.J., Hanchett, J!E. and Knepshield, J.H. (1972): Acute renal insufficiency due to
falciparum malaria. Review of 42 cases, Arch. Intern. Med., 129, 620‑6288 ) W, hite, N.E., Waller, D., Crawley. J., Nosten, F., Chapman, D., Brewster, D. and Grenwood, B.

M. (1992) : Comparison Qf artemether and chloroquine for severe malaria in Gambian children,
Lancet, 339, 317‑321

9 ) WHO (1990): Severe and complicated malaria, Trans. Roy. Soc. Trop. Med. Hyg., 84 (Suppl.
2), 1‑65

A CASE OF SEVERE MIXED PLASMODIUM FALCIPARUM
AND P. VIVAX INFECTION SUCCESSFULLY TREATED

WITH ARTEMETHERSHIGERU HOSAKA1, AKIRA ISHIKAWAl, TAKAO HosoNol,
YAYOI IIKUNll, HIROBUMI KoNDol, YUTATA KOBAYASHll,
TAKESHI NAKAMURA2, YOICHI IT02, HlROSHI OHTOM03

SHIGEYUKI KAN04 AND MAMORU SUZUK14
Received September 10 1992/Accepted October 14 1992

As the number of individuals traveling to malaria endemic countries increases, many
patients with malaria are increasingly being observed in Japan. Nevertheless malaria isliable to be misdiagnosed, incorrectly treated, and a severe course is thus not unusual.
However there are hardly any reports describing severe malaria in a Japanese patient due tomixed P.f and P. v. infection. We report a dase of severe malaria due to mixed P.f and P.
v. infection. The effectiveness of the new antimalarial drug, artemether, in the treatment of

this case of severe malaria is also documented.
A Japane e 31‑year‑old male wa admitted to Kitasato University Hospital because offever, diarrhea, and circulatory collapse. The history of this patient is that one week after
his return from a 9 day visit to Indonesia, during which he had weekly chloroquine prophyrax‑
is, developed fever and chills. He visited a hospital where he was treated for a common cold.

High fever was sustained and accompanied by watery diarrhea. On admissioh to our hospital,
his temparature was 40'C. The patient was lethargic but fully oriented and responsive. He

was dehydrated and peffusing poorly. Physical examination revealed jaund.! , , he‑patomegaly, and diffuse tendetness from the right costal margin to the epigastrium. P.f andP. v. were detected from a blood smear (12% and 0.7% parasitemia, respectively) . Oral

,

312

therapy with 600 mg quinine hydrochloride and 100 mg doxycycline was initiated. The nextday, his fever was unalterd, diarrhea and severe oliguria were evident. P.f parasitemia

increased to 29%. Antimaralial therapy was changed to 250 mg quinine hydrochloride
administered intravenously and fansimef, one tablet. Within 24 hr, he developed anuria anddrowsiness. Cerebral malaria was suspected and hemodialysis was started. Treatment withquinine was replaced by artemether. Two hundred mg of artemether was administered as
first dose intramusculary followed by 100 mg at interval of 12 hr, up to a total of 600 mg.
Examination of blood smear indicated complete elimination of asexual stages of the parasite,
within 38 hr after the onset of treatment with artemether. Thereafter, diuretic phase began

and the patient made a complete recovery. Histopathology of a renal biopsy specimen
showed tubular atrophy with interstitial lymphocytic infiltration, mild fibrosis and pigmented

casts, all suggestive of tubular necrosis but no glomerular involvement. Thus acute tubular

necrosis was considered as a cause of acute renal failure in this patient. To consolidate
artemether therapy and eliminate possible recrudescence, treatment with mefloquine wasinitiated, at the dose of 500 mg a day orally for 2 days. On the day the patient was discharged,

he was put on primaquine at the dose of 15 mg a day for 2 weeks. Forty‑eight days later,
despite the treatment given, he had fever and was diagnosed as a P. v. relapse case.

Treatment with chloroquine and twice as much primaquine cleared parasitemia. Fourmonths following this last treatment, the patient again had the symptom of fever and wastreated this last treatment, the patient was again had the symptom of fever and was treatedthis time with halofantrine and primaquine. Treatment with primaquine for 2 weeks wasfollowed by primaquine (45 mg) together with chloroquine (300 mg) once a week for 8
months. Serum anti‑P.f and P. v. IFAT titer profile of the patient over the entire course of
his treatment confirmed the clinical course of the disease.
The goal of the initial therapy of malaria is lowering the level of parasitemia as rapidly

as possible under strict intensive care with monitoring of vital organ functions. Artemether
was effective in achieving this goal even in this case of severe and complicated malaria due
to mixed P.f and P. v. infection.

1 Department of Internal Medicine, Kitasato University School of Medicine (1‑15‑1 Kitasato,
Sagamihara 228, Japan)
2 Department of Parasitology, Kitasato University School of Medicine
3 Department of Parasitology, Gifu University School of Medicine
4 Department of Parasitology, Gunma University School of Medicine

Jpn. J. Trop. Med. Hyg., Vol. 20, No. 4, 1992, pp. 313 323

313

Research Note

HEALTH, SOCIAL JUSTICE

AND THE THIRD REPUBLICFESTUS IGHAROSA AGBONLAHOR
Received October 25 1991/Accepted August 22 1992

Abstract: It is time worn to state that health is wealth. Yet this assertion is no lesstrue and significant today as it was yesterday. Indeed, a healthy nation is contigent on
healthy citizenry (Ist NDP) . This perhaps explains why no nation had ever attempted to
go to sleep while its 'health house' is on fire. In fact, the health of a nation defines its
potentials and actual deeds. The continual featuring of health in all the national develop‑

ment plans so far made, underscores the importance of the health of this nation's citizens

to our social planners. Be that as it may available , evidence shows a vaccum between
rhetorics and action. While no two analysts agree on the modalities of making health caredelivery services accessible to all (Steiner, 1966; Navarro, 1976; Titmus, 1966; Field, 1960) .

This paper is an attempt to contribute to this debate. Essentially, it warns that unless were‑order our priorities and achieve social justice in the health sector first, we may never

be in a comfortable position to discuss the issue of integration less alone meaningfulprogress in the third republic; come 1992, when the present military government hands
over power to a democratically elected government. Here lies the thrust.

INTRODUCTION
In his summation of the development of formal welfare scheme in Nigeria, Sanda (1987)

observed that health care in the period 1870 to 1910 was largely in the hands of theMissionaries even though the state coped with the health needs of the British soldiers throughthe Military hospitals in Zungeru, Lokoja and Zaria. The first world war period saw theestablishment of bush hospital especially around the war zones, while the depression of 1930s

and the discontent among the ex‑service men and the nationalist agitations all combined todirect the attention of the colonial government to the society's welfare needs. It was in thiscontext the laws of 1940 were made to cope with the labour and children welfare needs, the1945 ordinaces were directed at solving the problems of disabled soldiers and the 1948 Iaw
designed to enforce the obligations of families to under 14 children. By the same token,
workmen's compensation ordinance of 1941, 1945 and 1959 Iaws of the Federal republic of
Nigeria all tried to protect workers on matters of contract, injuries at work compesation,
forced labour, employment of young persons, wages, maternity leave and so forth. He thenconcluded by saying that the welfare structure that emerged became a combination of the

Bendel State University, P.M.B. 14, Ekpoma, Nigeria. This paper was first presented to the
Nigerian Anthropological and Sociological Association's Annual Conference on Social Justice,
National Integration and the third Republic held at the Ogun State University, Ago‑Iwoye, Nigeria

from the 26th to 9th November, 1989.

314

traditional pre‑colonial heritages with equal dependence upon the efforts of the voluntaryorganisations and government as well as the extreme regionalization before the advent of themilitary. It goes without saying that the various Nigerian governments since independence
have been aware of the 'welfare‑plight' of Nigerians (Ist‑4th NDP) . Be that as it may, theextent to which precepts have been substituted for action remains largely questionable. Aside
the fact of official default in pursuing the orthodox approach to health care delivery services

with all its curative emphasis, despite epidemiological reports which amply demonstrate thatthe bulk of the prevailing diseases in the tropics are preventable, reports concerning the stateof disrepair to which Nigerian health services have continued to be taken lightly by thegovernment of the day, while coup leaders now use such abysmal state of health as excusesfor taking over power. This is further exacerbated by a number of factors, among which are
the recent increase in brain drain which apperars to have hit the health sector hardest, thefact of a steady rise in population and most of all. The WHO's call for health for all by theyear 2000 (WHO 1978) .
It is right to acknowledge that the Nigerian government is aware of this situation andhave made a proposal for a health insurance scheme. However, the proposal as it stands now,
will not actualise social justice in health distribution as it is tailored to cater for only thegovernment 6 million work force and their 30 million dependants (The Guardian, Oct. l,1989) . What this means is that the injustices of not catering for the remaining 94 million willcontinue to be perpetrated. Besides, with a ceiling of 12,000 patients currently proposed andan average of 32 patients per day; to be attended by an unassisted doctor, the entire package

seems a panic measure designed to stem the tide of brain drain, by putting more money in theway of of the the medical doctor rather than improve the well being of the community.
Besides, if patients are to be wholly responsible for consultation and drug fees, the thequestion one would like to ask is whether the 'old and stale wine' has not managed to find it's

way into 'new wine skin'. It is with a deep sense of correcting this unjust situation that weare proposing a patially free and comprehensive package with universal coverage.

NATIONAL HEALTH INSURANCE SCHEME: A PROPOSAL
Epidemiological studies have made it possible for us to predict the incidences of diseases
in human populations. In taking advantage of this, various countries like Canada, Britain,

Denmark, Zimbabwe and a host of others have designed and implemented various forms of
insurance schemes, not the least, health; for their people. It is our firm belief that Nigeria can

do likewise.

Health insurance scheme, Iike all other social policies is designed to act not only as

checks in times of need, but also to conserve, protect and improve human responses(Friedlander, 1968; Rein, 1970) . For clarity, we shall discuss it under the following 3 headings,

namely: Scope, Finance and Method of provision.

SCOPE
The issue of what scope or range of people within a population should be covered byhealth policy is a fundamental one, with its consequences real. In addressing this issue,
various countries have adopted various styles. For example, in Britain, a series of social

315

schemes existed until the Beveridge proposal of 1946 that led to the national health insurance

scheme they have today. The same c'an be said for Canada, Denmark, New Zealand and ahost of others. Today however, most of these countries run a centralized insurance scheme.
The truth in the statement that the well‑being of a nation is dependent on the state of healthof its inhabitants suggests that we guarantee a minimum amount of health to every Nigerian.

It is in the light of this that we pestulate a compulsory, comprehensive and patially free
insurance scheme with a universal coverage for this nation.

FlNANCEThe issue of how to finance insurance scheme is no less complex (Steiner, 1966) . Again
in going about it, countries have always found it convinient to classify the population into
employers of labour, employees, the self employed and dependants. We subscribe to this but
would insist on the following modalities.

EMPLOYERS: A proportion of the total profits of all registered companies and those 'of
unregistered employers of labour be taxed. All newly established firms should however begiven three years tax‑felief period to enable them stabilize. The payment should be made at
the beginning or end of every financial year.

EMPLOYEES: All workers should be taxed to support the scheme. Such deductions should
be graded and should take the form of pay‑as‑you‑earn.
SELF EMPLOYED: A11 self employed people should be asked to pay a stipulated annual
flat‑rate to support the scheme. Like the employers, all newly self‑employed people should
be given a period of three years to stabilize. Besides, such rates should not be beyond theaffordable reach of this category and should not be too low to make others feel cheated.

DEPENDANTS: As the name implies, this category has no means of livelihood. At least notas yet, and so cannot be taxed. All these payments should be subsidized by the Federal
government which like the employer should reserve a percentage of the total revenue
accruing from the sales of all natural resources of this nation to support the scheme. Thiscan be further supported by the Federal, state and local governments by donating a part oftheir internally generated revenue to further fund the scheme.
PENSIONERS: By the same token, all pensioners are to pay a part of their earned income
as contributions to the scheme. Again, we recommend that such contributions should be
graded. This way, the scheme can be successfully financed, with the 'never‑sick' carrying the'ever‑sick'.

METHOD OF PROVISION
The fact that the bulk of the prevailing diseases in the tropics are preventable is no10nger in doubt. If anything, epiderniological researches have made it abundantly clear. It
is therefore to be expected that any proposal for health should take into account this salient

fact. We are therefore proposing a two‑headed prong: namely, preventive and curative
measures.

PREVENTIVE MEASURES: Here the Federal Ministry of Health is to pruchase drugs andare expected to organise periodic innoculations against the various contigencies of diseases

as it currently done uncer the expanded programme on immunization. It should devote a part316

of its buget to setting up schools for training public health educators and other paramedical

staff, who will inturn facilitate the implementation of its programmes,.

Since more than a tenuous relation exists between cultural practices and the occurenceof certain diseases in some areas (Meck, 1971; Oke, 1982) , it will be the duty of such public
educators to identify this relations and to point out why such people should invest in healthby discontinuing such practices. If this preventive measure is sufficienly carried out, it should
lessen the cases of ill‑health for curative attention.

CURATIVE: There are diverse methods of operating insurance schernes, as there arecountries. However, such method as may exist in a country, is usually dictated by thehistorical background, the needs, resources available and the acceptibility of the common useof such resources. Nigeria is currently into the era of privitazation. However, the herculean

nature of the task of maintaining a comprehensive health insurance policy with universal
coverage goes beybnd that of utilizing a private firm (Brieland, 1980) . It is in recognition ofthis that we recommend reliance on existing structures.
We propose that all government health structures in all three levels of government bemade the live‑wire of this programme. The assignrnent of the Federal as well as the state
governments should be limited to supervisory role. In this, the Federal Ministry should takeprecedence over the state, which should be seen as an organ for carrying out its directions in
the various localities.

All structures are to be regarded as existing in the local government where they arelocated, and steps should be taken to see that all local governments have at least a 200‑500
bed space hospital, that is adequately staffed. We suggest that the bulk of the cases should
be handled on out‑patient basis. Moreso when preventive dosage will be a part of the focus.
The actual running of the hospitals should be left in the hands of the governing councils or

management committees whose duty it should be to oversee and determine the budget of eachof such hospitals. Such persons as will be appointed should compose of staff of the Federal
or state ministry of health, in addition to limited members of staff of the hospitals and thoseof the public.

This should be followed by a direct call by the Federal Ministry of Health to its organs
in states, to register and maintain a record of people in their localities. Such registration

should be comprehensive enough to show the demographic arrtibutes of the people. More
importantly, it should show their ages, occupation and addresses. The duplicate of suchrecords should be sent to the Federal Ministry of Health which ideally should maintain acentral bank data unit on all localities.

Knowing the number of people by their social characteristics will further lend hand toascertaining the number of persons who fall into the categories of people to the levied and thenumber of dependents. This will faclitate planning. By the same token, a list of all doctors

who are interested in participating in the scheme should also be kept. All doctors alreadyworking for the various governments can either continue to work and receive their usualsalaries or can withdraw their appointments and take‑up contract like all other private
doctors interested in the scheme. Based on the list collected, both the doctors and patientsshould be divided on local government basis. After this, doctors should be given the list ofpeople they are to be ministering to. Such doctors should however have the powers of referralor even to consult other doctors in cases that need specialized treatment. This should be at
no extra cost to the patient.

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Again, the number of doctors to patient ratio.should be determined by the size and bed‑
space of their hospital. Doctors will be expected to be paid on item for service basis. This
principle should apply whether the service is that of a general practitioner, dentist, opthal‑mologist or surgeon. However, services by specialist should attract better pay than those ofgeneral practitioners. Another way to go about this is to utilize only specialists and remuner‑

ate commensurately. The advantage of item for service payment is that it will not only makepractice in this setting lucrative, but also stem the tide of brain drain. Such payments andceiling will be pegged by the governing council at the Federal Ministry of Health, so that a

uniform fee is adopted by all local government councils. All those who are working for theeffectiveness of this scheme, be they doctors, paramedical staff, monitoring unit, or part‑partgoverning council, should be remunerated from funds generated for the scheme. For effective
monitoring of operation and prevention of false claims, it is expected that only the healthcentres or hospitals to be cited at the local government headquarters should be utilized forthis scheme.
Patients may be allowed to change their doctors, but the right should be minimised a it
can be abused, and used only at discretion, as where lack of confidence is established, or
where a consenting note is issued by his/her personal doctor. In addition, such a person

should give four weeks notice giving reasons and preferences. All patients are expected toshow proof of eligibility. Only those who pay should be entertained. People out of theirstations can utilize any hospital of their choice on the production of an up‑to‑date proof of
subsctrption. What this means is that doctors may be allowed to treat patients outside theirlists, but this should not be more than a predetermined number and such cases should bereconcilled with his personal doctor in the locality.

Consultation with doctors for all patients should be free, but patiets should be made topay 75 per cent the cost of prescribed drugs. Hospitalised patients should pay 33.33 per centhospital bill and 25 per cent the cost of diagnostic tests and in cases where patients foot all
the bills, receipts should be submitted to the audit department of the hospital concerned, forreimbursement.
In order not to strangulate patients, government should produce and/or import most of

the drugs. This will help to keep the lid on the gain‑margins made by pharmaceuticalcompanies and hence reduce costs of health at the end of the day. Since doctors will form
the corner stone of this scheme, the least the supervisory body can do to guarantee fair play
is for it to set up in all the states in Nigeria, committee of insurance doctors to discipline

erring doctors or to refer the matter to the Nigeria Medical Association, which duty it is to
exercise this role. Finally, all this should be given the necessary legal backing.

DISCUSSION
The range of people to be covered by any National Health Insurance Scheme is some‑thing that all nations intending to establish such program must grapple with. Generally, thescope of any national insurance scheme is limited by a number of factors, foremost of whichis the nature of the scheme. For example, is it private or public? Under private insurance,

you have self‑help, which in the beginning of the insurance industry, involves a group ofpeople pooling resources together against the contigencies of diseases, ravages of fire andother forms of natural disaster. Private insurance could also involve the individual taking out

318

insurance policy on whatever contigency he wants to and lastly it could mean employers orunions making private arrangement to cater for the welfare of their employees or members.
One common strand that runs through all such arrangements is that it covers only those whotake them out or on whose behalf they are taken.
Private arrangement constitutes the principal form of insurance in Denmark, France andJapan. It is also the practice in most of the states in the United States, which in addition to

Switzerland remains the only two industrialized countries without resident compulsory
insurance (Enc. Britannica, 1987).

The other method of making provision for health insurance scheme involves the publicor government. The government of any nation can take steps to provide a range of social
security measures like housing, sanitation, transport, pension, old age, medicare and so on.
Coverage under public tutelage is limited by the aim of establishing the prograTnme and theresource availabl to the state. The latter is further predicated upon the magnitude andgeneral perception of the wealth. For example, a nation where all are agreed that no man
can ge self sufficient in the face of the unpredictable forms or dimensions of life's hazards, anddoes have the resources, are more likely to impress it on their government to make social
security measures a matter of priority.
Consequently, several countries have adopted modes, ranging from limited coverage ofthe population to full coverage. For example, 100 per cent coverage exists in the U.K. andin Cuba. Eighty per cent in Argentina, Brazil and Costa Rica. Fifty per cent coverage exists
in Uruguay, Mexico and Panama; while more than 25 per cent exists in Bolivia and Venezuela
whereas, others and in particular, African countries have less than 10 per cent (Enc. Brit.,1987) .

Differing approaches to coverage also exists. For example New Zealand extended
medical coverage to all residents in a number of stages. Beginning with free in‑patient
treatrnent in 1939, through out‑patient treatment and free pharmaceutical to part payment ofgeneral practitioners in 1941. Further steps were taken later on. And while India Govern‑
ment extends full coverage only to states that can maintain them, Korea extended healthinsurance only to her urban employed citizens (Enc. Brit., 1987) . Korean example is akin tothe one currently proposed by the Federal Government of Nigeria, where only the govern‑
ment six million work firce and their thirty million dependants are to be covered. The
injustices of this proposal is seen when this computed sum of 36 million is removed frorn thecurrent estimated population of 130 million (Sanda, 1986). This has far reaching conse‑
quences for health services in the rural areas where at leatst 90 million Nigerians live andwhere less than 10 per cent government establishments are located (Ist‑4th NDP) and for therealization of WHO's call for health for all by the year 2000 (WHO, 1978) . This perpetuatedsocial injustice as seen in the concentration of social amenities in the urban area to theneglect of the rural population, who in part provide, the bulk of the nation's wealth, is also

noticable in Kenya, Zimbabwe, South Africa, Ethiopia and a host of other African states(Dixon, 1987) . A further consequence of the above imbalance in the allocation of resources
between the rural and urban sectors, is that the greater part of the health vote is spent in theurban area. Sadder still is the fact that available records show that the latter is not withouta share of its injustice as most of the supposed urban vote end up under such ambiguous labels

like 'hospital programmes' which are cornpletely devoid of all services, be it preventive,
palliative or curative (3rd NDP).

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In our opinion, what is needed is a comprehensive preventive and curative man‑centred
national health insurance scheme, that will promote the health of everyman, not as found in
one occupational group or social class, but man as devoid of all social taxonomic concepts
and deserving a baseline guarantee by the society against the contigencies of diseases andother hazards of life that can debar him from living a fuller life.

Social insurance schemes anywher found are usually financed from contributions, derived

from the government, employers and employees. What makes the difference among countries
is the proportion in which these services are utilized. Chambers' Enc. (1973) reported thatwhen compared to Britain, which has universal coveage, the national scheme and pension
schemes in West Germany, France, and Italy, are characterised by their high contribution andbenefit rates and the smaller percentage contribution of the state. Whereas, in the unemploye‑

ment riddled Western Europe of the 1970s, the trend in Denmark, Ireland, Italy, The United

Kingdom, Portugal and The Netherlands, was that of shifting costs

way from employers

unto taxes. By the same token, Enc. Brit. (1987) reported that no cost falls on the limited

schemes in operation in places like Burundi and Ethiopia, and on the wider scheme in
Malaysia. Philippines and Singapore. Whereas, contributions play a very small role inAustria, Czechoslovaka, Denmark, New Zealand and the USSR, where the bulk of costs iscovered by taxation. National health insurance scheme in the UK is generally financed 50 per

cent from taxes and 50 per cent from contributions.
What we have established is that all societies are dynamic and at all times try to makesocial security measures as relevant and amenable as possible to the prevailing circumstancesand needs of their people.
Aside all the above listed sour'ces of funds for sponsoring national insurance schemes,
assitance by agencies also play a vital role in this exercise. In fact such programmes as thoseof the needy, aged, survivors and so forth, are supplemented with assistance payments inAustria, Czechoslovaka, France, West Germany, The Netherlands, United Kingdom and the
US. Yet the US and Switzerland, can be lumped together in another extreme as archtype
countries where tripartite financing as defined above is not practised. In fact, in the UnitedStates, such schemes are resisted by various organised bodies like the American Medical
Association which argue that it is unwise to socialize medical practice in a free enterpriseoriented country (Soc. sc. enc., 1968, Erinosho, 1981) .

All systems sponsoring national insurance schernes are faced by problems of actuarial
principles. They have to entertain such questions as to whether to make benefits related toprior earnings or whether needs should not take precedence. While this issue cannot becompletely resolved, countries have adopted differing measures which themselves haveinfluenced the state of health in such nations. For example, the United States adopted theearning‑related benefit, whereas the United Kingdom in addition to adopting similar measure
has introduced a floor to ensure that the common man is guaranteed some substainance levelor minimum standard of living.
Benefits under the scheme we are proposing are essentially medical and of service. Not
cash. We are contented to allow existing firms handle company injury as dictated by existing
union laws. What we are concerned with in this work, is laying a foundation for the take‑offof a national･ health insurance scheme with a universal coverage.
Experience has shown that contributions to national health insurance schemes and otherforms of social security designs, are strictly taxes on earned incomes. In our proposals, we320stated that the Federal Government, state, Iocal, employers, employees and pensioners are tobear the brunt of financing the scheme in Nigeria.' This is different from the practice of

asking the employers and employees to carry the greater part of the burden if what the

government is proposing comes through.
The advantage of asking the various arms of the government to contribute is obvious.
Nigeria lacks accurate census figure. The last estimate was 130 million. If we remove
government 6 million work force and 30 million dependants, we shall a staggering sum of 94
million uncartered for. Therefore, it would help to adopt a method that will involve every‑body.
The Federal Government like the state and local government councils, is to donate acertain precentage of all their internally generated revenue and should in addition, give a partof the proceeds from the sale of all natural resources of this country. This is the only way

the wealth can be held commonly.
In addition to the practice of taxing the employer and employees as individuals, we
proposed that both be taxed accordingly and for the company to be taxed as a corporate
body. The benefit of giving tax relief to newly established companies is seen in the fact thatnot many large corporations exist in Nigeria, and while many are still out of jobs, making
employers pay part of the insurance for each employee, may be good in the short run but
might prove reptogressive in the long run as it will probably lead to utilizing short cuts tocontibution liability like giving jobs out on contract for a money wage, introducing overtime

or even retrenchment. A phenomenon that will further worsen the already soared labour
market. As for the argument that it is socially unjust to tax the employers as well as the
profit of their corporation, we feel it is the least they can do to keep the systern going. In any

case, reports exist to show that employers' contributions are not always paid at the expenseof profit (Enc. Brit., 1987). Besides Romanysyn (1971) bas argued that all welfare pro‑gramme does is to maintain the discipline of work and in real term ensures that somebody
will be around to do the dirty job and by so doing, prevent people from probing into the more

fundamental question of the causes of dependency. And while such thoughts are also inherent

in the work of Filgerald (1977), De Schweinitz is of the opinion that the question of
inequality would not have arisen if all it takes is the ability to contribute to society. This

reason also underlay and serves to highlight the sharp difference in our proposal as against

existing ones where governments set up special funds to run insurance schemes rather thancontribute from its main revenue as we advoated.
We also proposed that a proportion of all pensioners' allowance be taxed to support thescheme. The tax should be graded and should take th form of pay as you go. It is common
knowledge that the aged ih all societies spend more on health than workens. Again, in asituation where we are proposing a universal coverage, it is only right to include all
beneficiaries with known sources of income. Steiner (1971), has also made this call.
Enc. Brit. (1987) Iists three modes of provision of health insurance benefits, namely;

direct, indirect and reimbursement. Under direct service approach, the government orsponsoring body owns the facilities which include hospitals and clinics. It also pays for the

supply of drugs and remunerates all staff. As the name implies, this is a direct contrast of

the second method which entails the funding body making contract with people who provide
and get remunerated accordingly. Whereas patients foot the entire bills and later submit
them for claims in the third category.

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A comparative study will show a preponderance with any of these methods. Reimburse‑
ment for example is largely used in France and to some extent in Australia and Sweden. The
indirect method is heavily utilized for all services in such countries as Belgium, Westbermany. Luxembourg and The Netherlands. Whereas the direct mode is employed in The
UK, Scandinavia, Greece, Spain, Portugal and a host of others.
At a glance, this forms represent a tendency towards regidity. Habit has however shown
the contrary. Indeed countries use a combination of these at any point in time, with theemphasis on any particular method dictated by the global configuration, the socio‑economic
and political order of the day. For example, aside employing the direct method, the national
insurance scheme in Britain utilizes indirect contract for general practitioner, community
pharmacist, opticians and most dentists. The same phenonrnenon is said to be at work in
Greece, Italy and most latin American countries (Enc. Brit., 1987). This observation can bemade for our proposal wihch utilizes the direct method in the main but also insists on the third

category where patients end up footing the bills.

In writing this paper, we made a number of assumptions:
1 . That since men live in an organised community, the society owes it as a duty to provide
a basic social security measure especially in the light of the contigencies of diseases andother forms of hazards the individual is ill‑equiped to grapple with.
2 . Inherent in the above is the assumption that health is an inalienable right of all citizens

and should remain so if human societies are to make meaningful progress.
3 . Bearing in mind. the concept of social justice, we have implicitly argued that the wealthof Nigeria belongs to all Nigerians and should be maximally used for the benefit of all
if we are to develop.

4 . That when once we identify health as an active ingredient of development, the advocacythat it be accessible, cornpulsory and cornprehensive is not too difficult to follow.

5 . That to undermine these assertions is to support arbitrary and continuous duplicatedhealth policies, to undermine the very health of the uninsured 94 million Nigerians witheach of them automatically turned into a melancholic agent of development, to threaten
the survival and well being of the nation as well as render the principles of integrationand meaningful progress in the third republic redundant.

The days of the much celebrated Daniel Defoe's hero‑Robbinson Cruso has come to an
end in most countries of the world (Crampton, 1972; Smelser, 1966; Titmus, 1966). Today,
men are no longer thought to be masters of their fates who must, following the principles ofsocial Darwinism which pervaded western societies of the 19th century, engage in stiffcompetition for existence and reap the full consequences for his action or inaction. Indeed,
it would appear that the definition of society which emphasis interaction has made increasing‑ly impact on the leaders of men. Whether this phenomenon has its roots in the discoveringof the fact that poverty has a direct relation with the social institutions that determine theallocation of personal and social resources needed for existence and competing for positions

and power as Romanyshyn (1976) has hypothesised, or the benevolence act of a mover‑unmoved, sufiice to say that developing nations are aware of this and are atuning themselvesmore to the well‑being of their peoples. Sadly however, a great gap still exists between
precepts and" deeds in most of these countries. The problems of implementing a national
health insurance scheme are diversified, and range from the presence of resourses, manpower
to planning. We strongly believe that Nigeria has the resources to set up such a scheme if

t

322

properly managed. Tawney (1966) must have had Nigeria in mind when he argued:
Health . . . is a purchasable commondity, of which a community can possess, vithin limits

as much as it cares to pay for. It can turn its resources in one direction and 50,000 of its
members will live who would otherwise have died. It can turn them in another and 50,000 will

die who would otherwise have lived.

REFERENCES
1 ) Batten, T.R. (1960): Communities and their development: an introductory study with specialreference to the tropics, Oxford, London
2 ) Brieland, D. (1980): Contemporary social work: an introduction to social work and social

welfare, McGraw‑Hill, New York3 ) Chamber's Encycopaedia Vol. XII (1973): International learning system, London
4 ) Crompton, H.M. and Keiser, K.K. (1970) : Social welfare: institution and process, Random

House, New York5 ) Dixon, J. (ed.) (1987): Social welfare in Africa, Croom Helm, London
6 ) Encyclopedia American (1981): (Vol. 25), International ed. Grolier, Danbury
7 ) Encyclopedia Britannica (1987): (Vol. 27), 15th ed., Chicago
8 ) Erinosho, O.A. (1981): Health planning in Nigeria: a critique, Department of Sociology,
University of lbadan, Ibadan
9 ) Federal Republic of Nigeria (1970) : Second national development plan 1970‑75 Lagos; Federal
Ministry of Information Printing Division10) Federal Republic of Nigeria (1975): Third national development plan 1970‑80 Lagos; theCentral Planning Office, Federal Ministry of Economic Developmentll) Federal Republic of Nigeria (1981): Fourth national development plan 1981‑85 Lagos; The
National Planning Office, Federal Ministry of National Planning12) Field, M.A. (1960): Structured strain in the role of the Soviet physisian; in medical care by

Scott and Volkart, John Wiley, New York13) Fieldlander, W.A. (1968) : Introduction to social welfare (3rd ed.), Printice‑Hall, New Jersey14) Hay, J.R. (1977): The origins of the liberal welfare reforms: 1906‑1914, Macmillan, New York

15) Konopka, G. (1963): Social group work: a helping process, Printice‑Hall, Englewood Cliffs16) Marshall, T.M. (1976): The right to welfare, in talking about welfare: readings in philosophy
and social policy, N. Timm and D. Watson (eds.):, Routledge and Kegan Paul, London17) Meck, M. (1971) : Problems and prospects of social services in Kenya, Welforum Verlag Gamb

H, Mtnchen18) Meyer, C.H. (1970) : Social work prctice: a response to the urban crisis; Free Press, New York19) Navarro, V. (1976) : Medicine under capitalism, Prodist, New York
20) Oke, A. (1982): Social epidemiology; studies in third world societies, No. 3
21) Okediji, F.O. (eds.) (1972): The rehabilitation of beggers in Nigeria; University of lbadan
Press, Ibadan
22) Rein. M. (1970) : Social policy: issues of choice and change, Random House, New York23) Romanyshyn, J.M. (1971): Social welfare; charity to justice, Random House, New York24) Sanda, A.O. (1987): Social welfare in Nigeria; in social welfare in Africa, op. cit.

25) Saville, J. (1977): The welfare state: an histological approach; in welfare in action: M.
Fitzgerald et al., (ed.), Routledge and Kegan Paul, London
26) Schweinitz, K.D.Jr. and Thompson, K.W. (1953): Conflict ahd choice in the industrial era,

Henry Holt, New York27) Smelser, N.J. (1966): The modernization of social relations, in the dynamics of growth, M.

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Weiner (ed.):, Basic Books, New York28) Steiner, G.Y. (1966): Social insecurrity: the politics of welfare, Rand McNally, Chicago
29) Steiner, G.Y. (1971): The state of welfare, The Bookings Institution, Washington30) Titmus, R.M. (1966): The national health services in England; some aspect,s of structure; incomparative social problems, S.N. Eisenstadt (ed.), Free Press, New York
31)

Titmus, R.M. (1968): Commitment to welfare; Pantheon Books, New York32) WHO (1978): Primary health care: report of the international conference on primary healthcare, Ahma‑Ata, USSRJP . J. T**P. M*d. Hyg., v*1' 20, N . 4, 1992, PP.325‑332 ' 325

Research Note

THE INTEGRATION OF TRADITIONAL HEALESINTO THE MAlN‑STREAM OF OUR HEALTH CARE
DELIVARY SERVICES: A RE‑APRAISALFESTUS IGHAROSA AGBONLAHOR
Received October 25 1992/Accepted September 1 1992

Abstract: This paper is essentially theoretical and attempts to re‑appraise the issues
involved in the call for the integration of traditional healers by the WHO. In order todiscuss in perspective, it focusses on the Nigerian situation and demonstrates why integra‑
tion represents a more viable avenue to the realization of 'Health for all by the year 2000

AD'. The paper winds up suggesting a modality for achieving this.

When the day shall dawn upon us from on high to give light to those who sit in darkness
and in the shadow of death . . . Luke 1:79.

HEALTH PLANNlNG
Erinosho (1981) has argued that health planning for developing nations: . . . is aimed atensuring for the average citizen in the population, access to medical care and other basic
facilities which would enable him/her to attain a reasonably high health status and life longexpectancy.
It is given therefore, that the efforts of health personnel will be geared towards achieving

this goal. Even then, such methods as employed have however, never been divorced from thediffering state ideologies and consequently, their political economy. For Unscheuld (1976) ,the medical system of any society has to do with the distrubution of the health resources inthat society. A Iook at the pattern of health care delivery services in the USA, and USSR will
epitomise this.

THE US MoD L
The capitalistic economies of the United States and nay, of all Western World ispredicated on a regulated free enterprise. Although evidences abound to show strong elementof welfarism: in the United States health care delivery service is left at the whim andcaprises of enterpreneurs who act as fronts to the various insurance companies that exist to
fill the vacuum of the provision of health care (Anderson, 1963) . Under such an arrangement,
Erinosho (1981) noted that "the citizenry is at the mercy of those companies which invariably
derive substantial profits from the sale of health policies".

Department of Sociology, Bendel State University, P.M.B. 14, Ekpoma Nrgerra

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THE USSR MODEL
Health care delivery services in the Socialist Soviet Union and indeed all Eastern bloc,
seems to operate on the premise that building a healthy nation is contigent on having healthy
citizenry. The state ‑as typical of this bloc‑ therefore, sees it as obligatory on her, to provide

health needs for all her citzens. Little wonder she directly intervenes in all ramifications of

the provision of health services; in order to meet this goal (Field, 1966). This therefore,

explains the phenomenon of relatively low cost of sophisticated health shopping enjoyed by
the people of this bloc.

THE NIGERIAN MODEL
In Nigeria, medical system is organised along Euro‑america model. Orthodox medicine
exists side by side with traditional medicine, even though, the latter and older is yet to begiven official recognition by the government (Oyebola, 1981) .

As a medical system that was borne out of colonial experience, orthodox medicine
emphasizes curative rather than preventive health services: whereas, social epidemiologicalresearch reports have made it abundantly clear that by far greater proportion of the diseases
prevalent in the tropical Africa are preventable. The implication of this is that reliance on

orthodox medicine alone will not actualize 'health for all by the year 2000 AD'.

Orthodox medicine is founded on science and as a varifiable knowledge limits its
explanation only to what it can empirically varify. As a practice that is guided by scientificethics, modern medicine restricts its explanation to germ theory which explains diseasecausation in terms of physical or biological discontinuity resulting from such things as insect

bites, bad odour, habitation in unhygenic environment and so forth (Erinosho, 1981; Oke,
1982) . But while it is true to say that the refiection of scientific ethics in modern medicine isin consonant with the world view of western societies, it is right too to say it goes beyond thisfor the African whose explanation, in addition to taking cognisance of the physical world also

incorporates the psyche realm (Oke, 1982; Erinosho, 1981; Gluckman, 1963; Armntrong, 1971;
Macleans, 1971; Impareto 1975; Chilivumbo, 1976; Unschuld, 1976) . This insufficiency is mostnoticably in the illness behaviour of Nigerians. Cases have been heard where hospitalized
patients secretly have their relations bring them traditional medicine (Asuni, 1979; Osunto‑
kun, 1975; Tory. Sunday Guardian, Feb. 10, 1986).

Other problems centre around the urban based nature of orthodox medicine which
encourages the scanty number of personnel she parades to cluster around urban centres, brain
drain, high cost of training paramedical pernonnel and that involved in purcahsing neccessary
equipment. The list is endless. It can be argued that it is the recognition of the flaws in theorthodox system; particularly its variant position with epidemiological reports, that havemade the Federal Government of Nigeria to engage in the Expanded Programme on Immuni‑
zation (EPI).

Again, while it is true to say that Nigeria has everything to going by engaging in thisprogramme, it is relevant too to mention that analysts see it as another 'urban' project. These

facts if coupled with the knowledge that over 2/3 of Nigerians live in the rural area and are

ill provided with medical facilities (WHO, 1975; Ademuwagun, 1969. 1976; Olatundosun,1975) ‑will better enable us to grapple with or appreciate the works of scholars who have

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called for an alternative approach which favours preventive services rather than curative.
This approach is quite apt and no doubt constitutes a viable alternative to the present
system. Moreso as it favours epiderniological reports stated earlier. Yet attractive as thisapproach may seem, it is the contention of this paper that the modalities for implementing it

is fraught with numerous problems capable of making us lose sight of the very essence of
health care delivery services. Indeed, as Rosett (1967) , rightly observed, the difficulty is thatwhen reforms are attempted at a deeper level ". . . new problems arise to replace the old".

We contend that the physicians who undoubtedly derive great importance from thepresent arrangement are in all probabilities likely to unleash all the powers at their disposal

including lobby by such accredited bodies as the Nigeria Medical Association (NMA) ahd
National Association of Resident Doctors (NARD) to frustrate such moves. While this isgoing.on, the very essence of the whole affairs will in all certainty be disrupted and evetually
def eated.

THE RATIONAL WAY OUT
In the light of the foregoing, we strongly advocate that the only effective means ofactualizing health for all by the year 2000 AD is to follow the directive of WHO (1978) tointegrate the traditional healers into the mainstream of health care delivery services in
Nigeria.
A traditional healer is defined by WHO (1977) as: . . . a person who is recognised by thecommunity in which he lives as competent to provide health care by using vegetable, animaland mineral substances and certain other methods based on social cultural and religious

background as well as on the knowledge, attitudes and beliefs that are present in thecommunity, regarding physical, mental, social well being and the causation of disease anddisability.

This call for integration hardly needs substantiation. It is cheap and efficacious (WHO,1978; Elling, 1981; Maclean, 1969; Ademuwagun, 1969; Prince, 1960; Otsyula, 1973) . Eighty percent Nigerians are already used to going to them (Oyebola, 1980; WHO, 1975; Lambo, 1966;
Harrison, 1974). It adequately captivates the world view of the Africans (Ndeti, 1976;
Chilivumbo, 1976), and they are available in all localities (WHO, 1975).

ANTICIPATED PROBLEMS FOR INTEGRATION
One big tragedy for integration, is the lack of unanimity among scholars on the issue of

how best to go about it. For example, while some of the scholars favour the idea of the
traditional healers working side by side with medical doctors in the hospital setting, others

think otherwise. The main arguement advanced by the former is that it will be cheaper andquicker to assimilate them that way. This stance however creates more problems than itsolves. It neither takes into account the social‑cultural context from which it seeks to invite

the traditional healers nor takes into consideration, the present attitude of Nigerian
physicains to the healers. It suf ce to say for now that those social scientists who have hadcourse to work with the medical doctors in the hospital setting have said it requires a lot of32 8'thick skin'.

We therefore, suggest that one way to achieve full integration and hence health for all
by the year 2000 AD is for the traditional healers to remain in their persent setting. This will

tentatively remove the issue of standardized concepts, eliminate complexes and accommo‑
date role confiicts like how close to get to the patients, at what stage of diagnosis should the

traditional healers be called in and whether or not to make or take diagnosis jointly.

In a recent study, the researcher discovered other problems capable of frustrating thiscall for integration. One of such is the literacy level of the traditional healers. A total of 44%of the traditional healers fell into the stark illiterate cohort and another 44% into the semi‑

lit rate category; whose educational attainment ranked below senior secondary one. We
linked this with the Universal Primary Education prevalent in the then Western region. It istherefore, doubtful if other healers in regions that did not run this programme would not ranklower
A more fundamental problem is that of concretising the spiritual world. Science does notrecognise what is cannot see. So how do we take seriously the claims by healers to be able
to carry out healing arts with the aid of the supernatural? Is this a mere belief, in which casehaving something to do with the psychological disposition of the mind or is it realitic?
Exactly to what extent can it be relied upon to yield the same result from time to time?
Other areas of problems include the purification healers drugs, Iack of accurate dosage
and that of procuring a winowing machine to help sever 'grain‑healers' from 'chaff‑healers'.
We strongly believe that it is the partial recognition of some of these problems and the threatof integration to the status quo that have made some scholars and especially the modern
practitioners to continue to asymetrically or lopsidedly utilize their present access to thesource of power, to pass derogatory and deprecating comments on the persons and works ofthe traditional healers (Daily Stetch, Monday Jan., 20, 1986; Ndeti, 1976; Oyebola, 1980;
Bannerman, 1981; Torrey, 1972). Even then we have reasons to believe that these problems
are not insurmountable. It took time to build those well organised Euro‑america model theexcellence of which the Nigerian Physician now strives to achieve, despite its high cost andill suitability for the tropics.

RECOMMENDATIONS
It is our expressed view that the only way the traditional healers can be integrated andlogically health to the door‑step of all by the year 2000 AD, is for the Federal Government

to recognise them. There, is no other way out. Oke (1985) reported that 79% of his
respondents were quite willing to heed WHO's call for integration. My field experience andthe work of Erinosho (1985) further served to confirm this.
2 . Ofiicial recognition should be followed up by the setting of an all exclusive traditional

healers board, by the Federal Government. This body should be charged with drawing up a
uniform code of conduct for all registered traditional healers in the country and be given
power to deal with erring members and fake healers (unregistered healers) .
3 . The Federal Government should then direct the various state governments to follow suitin setting up an all exclusive healers board. This board should be composed of healers fromall the local government areas. Again, representation should be on equal basis.
4 . The state boards should be responsible to the one at the federal level and infact should

32,9

be seen as an organ for meeting its ends in the country.
5 . The Federal Board should then direct all the state boards to register all ohe traditional
healers in their state by their specialization. Such registration should be on local government
basis.

6 . Numbers three and five functions if properly executed should winnow quack healers. It
should also enable us to have a proper categorization of the various branches of traditional
medicine in Nigeria.
7 . To disband the present multifarious traditional healers association in all the shapes andsizes and to set up state association to which all registered members must belong.
8 . This body should be an arm of the Federal body which should have a Federal Secretariat.
9 . The State bodies should have final say in the prosecution of quacks and erring members,
but offenders should be allowed to appeal to the Federal level, should they feel disatisfied withthe judgements. Such rights however should not be extended to quacks‑or registeredmembers, We recommend that the quacks and dismissed practitioners should only practiceat the risk of being prosectuted.

10. The Federal Government should assist the Federal healers' Board to set up aphamacological research body to determine both the medicinal potency and the chemicalcomponents of herbs.
11. In this bid, the assistance of the various states should be enlisted.

12. Based on the above, the phamacological body should come up with a classification of thelist of traditional drugs in Nigeria.

13. To device effective ways of diseminating the results of such efforts at standardization ofherbs. The above if conscientiously executed should standardize our drugs and by so doingtake care of the issue of over doze and that of the purity or refinement of healers' drugs.
14. To tackle the problern of low literacy rate by organizing symposia debates and seminars
in which members will be schedule to talk; not necessarily in English, and for adequate
coverage to be given to such gatherings.

15. To further encourage healers by empowering the Board to recruit and train for a
maximum of two years, school certificate holders who will act as interpreters to healers intheir various local governments secretariat if need be and/or translate in native dialect andbroadcast the activities.

16. The Government can help to reduce to level, the blases of medical practitioner by
allowing Erinosho (1981) to persuade her into inculcating in the curricula of medical educa‑tion in Nigeria, knowledge of the "ubiqmtous socral cultural factors which underlre thecontigencies of medical care in tropical Africa".

Erinosho's suggestion if adopted will help the physicians to understand and better copewith the illness behavious of Africans. It will help the doctors to know that Africa is still aface to face society where relationships with kins and neighbours matter a lot. This will playdown on their present tendency towards impersonal services. This is the key to the havenpatients flnd in the homes of the traditional practitioner (Oke, 1982; Erinosho, 1981) ,Furthermore, implementing Erinosho's recommendation will as said before, correct thepresent attitudes of physicians to healers. This will set off a chain of reactions like reducing

complexes, resolving numerou

role conflicts like the issue of how close to get one's patients;

foster accommodative atmosphere that will eventually culminate in the working side by sideof the traditional healers and the medical doctors in the hospital setting.

330

When this happens we cannot but agree that a new dawn has arrived. The common man
will wax stronger in health and Nigeria will thrive. We have no doubt whatsoever that suchan ideal state of a nation's health can be achieved if we integrate our traditional healers into
the 'midstream' of our health care delivery services. The time to start is now.

DrscUSSION
A search for a viable alternative in the corridors of the medical systems of Euro‑america
and the USSR can not guarantee health for all by the year 2000. Today, Nigeria operates the

Etiro‑america model. But it is too riddled with insufficiently syndrome to be relied upon.
Today 80% of Nigerians live in the villeges and are ill provided with medical facilities.

Therefore, a model which will be accommodated by the operators of the present system
will be best adopted in the interest of our continued existence. This model calls for the
integration of the traditional healers into the 'midstream' of our health care delivery services.

This seemly new model is not new. In China and USSR traditional healers work side by sidewith the medical doctors, and are doing quite well (Prince, 1964; Maclean, 1966) . Perhaps itis the perfection of such wedlocks, coupled with epidemiological reports and insufficiency

syndrome that made Maclean and Bannermann (1982) , Ademuwagun (1969) , WHO (1973) torecommend this mtegration "dose" to ailmg third world countries. A trillion voices cannot
be wrong. A healthy nation is contigent on healthy citizenry.
Here I rest my oar!

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Research note
Agbonlahor, F.1.
Health, Social Justice and the Thifd Republic ""'Agbonlahor, F.1.
The Integratiu n of Traditional Heales into the Main‑stream of Our Health Care
Derivary Services: a Re‑apraisal･･････････････････････‑

313‑323

325‑332ISSN 0304‑2]46

JAPANESE JOURNAL OF
TROPICAL MEDIClNE AND HYGIENE
December 1992

Vol. 20 No. 4

CONTENTS
Review
Takaoka, H.
Pathogens of Blackflies in Guatemala and Their Infiuence on Natural Populationsof the Three Onchocerciasis Vectors

251‑259

Omar, B.B.
Phylogenetic Relationships Among the Genera of Dirofilariinae

Sandground, 1921 (Nematoda: Onchocercidae)

261‑270

Original article
Shichinohe, K., Shimizu, M., Kato, K., Tamura, N., Tsukidate, S. and Fujita, K.
Basic Studies on the Mongolian Gerbile as a Susceptible Host to Filarial
Infection; IgE‑like Antibody Formation Against Dirofilaria immitis

Adult Worm Antigen
Ani, A., Takahashi. M., Saida, H., Taniguchi, H., Takahashi, T. and Sato, M.
Bacterial Diarrhoeas in Jos, Nigeria
Kimura, A., Minekawa, Y., Ikeda, N., Shimoirisa. K., Kusui, Y., Matsumoto, Y. and271‑281283‑290

Nakabayashi, T.
Survey of Giardia lamblia Infection in Returning Travelers with Diarrhoea from
India and Nepal at Osaka Airport

Quarantine Station (in Japanese) """""""""

291‑297

Case report
Yodonawa, S., Kano, S., Saito, T., Yokoyama, Y., Kawai, S. and Suzuki, M.
An Imported Case of Vivax Malaria Treated with Halofantrine(in Japanese)
Hosaka, S., Ishikawa, A., Hosono, T., Iikuni, Y., Kondo, H., Kobayashi, Y.,
Nakamura, T., Ito, Y., Ohtomo, H., Kano, S. and Suzuki, M.

A Case of Severe Mixed Plasmodium falciparum and P. vivax Infection
Successfully Treated with Artemeter (in Japanese)(Contents continued on reverse of this cover)Jpn. J. Tro p.

Med. Hyg.

JAPANESE SOCIETY OF TROPICAL MEDIClNE

299‑303305‑312