On the genus Gnathostoma and human gnathostomiasis, with special reference to Japan

EXPERIMENTAL

PARASITOLOGY

9,

338-370

(1960)

PARASITOLOGICAL

REVIEWS

SECTION

* * * * *

On

the

Genus

Gnathostoma Special

and Human Gnathostomiasis, Reference to Japan’ Ichiro

Department

oj Parasitology,

Faculty

Miyazaki

of Medicine,

Kyushu

Introduction ........... ............................ Gnathostoma spinigerum Owen, 1836 .................. 1. Geographical distribution ....................... 2. Morphological features of the adult worms ........ 3. Life history ..................................... 4. Natural infection of the final host ....... ........ 5. Natural infection of the second intermediate host. Gnathostoma doloresi Tubangui, 1925. .................. 1. Geographical distribution. ........................ 2. Morphological features of the adult worms .......... 3. Life history ...................................... Gnathostoma nipponicum Yamaguti, 1941.. ..... 1. Morphological features of the adult worms. 2. Life history. ............................. Gnathostoma hispidum Fedchenko, 1872 ......... 1. Morphological features of the adult worms. 2. Life history ............................. Gnathostoma procyonis Chandler, 1942. ........ 1. Morphological features of the adult worms. 2. Life history. ........................... Gnathostoma turgidum Stossich, 1902. .......... Gnathostoma american,um Travassos, 1925. ............... Human gnathostomiasis. .......................... ..... 1. Source of human infection ........................... 2. Symptoms ............................. 3. Diagnosis ........................................... 4. Treatment, and prevention ......................... References ..............................................

The genus Gnathostoma was founded by Owen in 1836, the genotype of which was called Gnathostoma spinigerum Owen, 1836. This nematode was first discovered by him in the stomach wall of a tiger which died in the London Zoological Gardens, and now is the most important speciesof the genus as * Aided Ministry

by a Scientific of Education,

Research Japan

Grant

from

with

the 338

University,

Fukuoka,

Japan 338 340 340 341 348 346 347 347 348 348 350 353 353 354 355 357 357 358 358 358 359 360 360 361 362 364 364 365

the causative agent of the human gnathostomiasis. Subsequently, 18 speciesof the genus have so far been reported from different kinds of animals in various localities. Table I shows 19 speciesof the genus hitherto reported in the literature, together with their type hosts, their habitats in the final hosts and the localities where they were first discovered. Some of them, however, seemto be not distinct species. The author is carrying on the study of taxonomy of the genus, and has so

HUMAN

TABLE Gnathostoma

hitherto

-

339

GNBTHOSTOMIASIS

Species of Gnathostoma

I Reported

Type

host

in Literature

Habitat

Locality

1. 2. 3. 4.

G.spinigerum Owen, 1836 G.robustum(Diesing, 1838) G.gracile(Diesing, 1838) G.horridum(Leidy, 1856)

5. G.sociaZe(Leidy, 6. G.radulunL(Schneider, 7. G.hispidum

1866)

Fedchenko,

8. G.pelecani(Chatin, 9. 10. 11. 12. 13. 14. 15. 16. 17. 18.

1858)

1872 1874)

G.siamense(Levinsen, 1889) G.turgidum Stossich, 1902 G.paronai Porta, 1908 G.accipitri Skrjabin, 1915 G.americanum Travassos, 1925 G.doloresi Tubangui, 1925 G.dideEphis Chandler, 1932 G.nipponicum Yamaguti, 1941 G.procyonis Chandler, 1942 G.minutwn Stekhoven, 1943

19. G.brasiliense

Ruiz,

1952

Felis tigris Felis concolor Arapaima gigas(fish) Alligator rnississippiensis M ustela vison(mink) Paradoxurus philippinensis Sus scrofa ferris & Sus scrofa domesticks Pelecanus onocrotalus

1.

Homo sapiens Didelphis azarae RatttLs rajah eagle Felis tigrina Sus scrofa domesticus Didelphis virginiana JlfLstela sibirica itatsi Procyon lotor lotot serpent

Lutreolina

crassiraudata

Stomach Stomach Intestinal Stomach

wall wall canal lumen

England Brazil Brazil U. S. A.

Stomach Stomach

wall wall

U. S. A. Philippines

Stomach

wall

Turkest Hungaq

Subcutis sac Subcutis Stomach Intestinal Subcutis(?) Stomach Stomach Liver Esophageal Stomach Connective sue Liver

&

an &

ai; r Thailand Argentina Mentawei Islands Turkestan Brazil Philippines U. S. A. Japan u. s. A. Belgian Congo

wall canal wall wall nal’ I wall tis-

Brazil -

far investigated not only three species occurring in Japan, but also several specimens from foreign lands through the kind cooperation of the late Prof. A. C. Chandler, Dr. L. R. Ash of Tulane University Medical School, U. S. A., Prof. Y. C. Hsu of the First Medical College of Shanghai, China and Dr. K. Wada in Bangkok, Thailand. The foreign species which the author could examine by himself were G. spinigerum in Thailand, India and China, G. hispidum in China and G. procyonis, G. didelphis and G. sociale in U. S. A. Of the species shown in Table I, G. pelecani, G. accipitri and G. minutum were all found in larval form, so that their specific names are very doubtful; they seem to belong to G. spinigerum. The type specimens of G. siamense, G. didelphis and G. brasiliensv were sexually immature, and the first species is now regarded as G. spinigerum and the ot,her two may be synonymous with G. twgidum. G. gracile, G. horridum and G. paronai, which were accidentally found in

unnatural habiteat of unnatural hosts, are very diflicult to re-examine and discuss. G. radulum seems,as Baylis and Lane (1920) already stated, to be the same as G. spinigerum. G. americanum may probably be identical with G. robusturn, because both of them were found in Brazil and their type hosts belong to the same genus. However, it is necessary to compare them exactly in the future. G. sociale is generally considered to be identical wit,h G. spinigerum, but the aut’hor thinks that it is not invariably t>rue because of considerable difference of their geographical distribution and t,heir type hosts. By the courtesy of the late Prof. Chandler, the author was able to examine one male specimen of G. sociale deposited in t)he Carnegie Museum U. S. A. However, the fore-body of the specimen was already lost, so that it was impossible t,o compare it with G. spinigerum in *Japan.G. sociale needs more exact re-examination. In conclusion, t’he author is inclined t,o think that the certainly dist,inct) speciesare

340

MIYAZAKI

seven in number; i.e. G. spinigerum, G. hispidum, G. turgidurn, G. americanum, G. Bdoloresi,G. nipponicum and G. procyonis, of which spinigerum, doloresi and nipponicum are distributed in Japan. In order to differentiate these speciesin the adult stage, it is most important to investigate the extent and the shape of cuticular spines all over the body. The size and shape of eggs are also available for this purpose. Some people set much value to the number of caudal papillae of males, but from the author’s experience it seems unwise to do so, because the small ventral papillae are very easily overlooked.

extensively and deeply studied mainly in Thailand, the Philippines, China and Japan. In our country the first finding of this species was reported by Yoshida et al. (1936), who found unexpectedly seven adult worms in two cats in Osaka Prefecture, Honshu. After World War II, the study of this worm was begun mainly by the author and his coworkers in the northern part of Kyushu. 1. Geographical Distribution

The worm is widely distributed in Asia, i.e. in India, Ceylon, Burma, Thailand, Malaya, Indonesia, the Philippines, China (mainland), Japan and moreover in AusGNATHOSTOMA SPINIGERUM Owen, 1836 tralia. In Japan, the co-operative research on From the medical point of view this species this problem has been continued by the is the most important, causing almost all author and his co-workers in 1955-1957 casesof human gnathostomiasis in the world; under a subsidy from the Ministry of Educaaccordingly this nematode has been most tion, and the results obtained are shown in

FIG. 1. Distribution of G. spinigerum in Japan. The solid black prefectures are infested; there patients occurred and larval gnathostomes were found in the fish OphicephaZus. Solid circles indicate the prefectures where some cases occurred, but no larval gnathostome has yet been found in Ophicephalus. In the stippled prefectures the larval gnathostomes were found in birds, but not yet in Ophicephalus.

HUMAN

341

GNATHOSTOMIASIS

Fig. 1. Of 11 prefectures, where the worm is indigenous, Fukuoka and Saga in Kyushu, Kagawa in Shikoku and Hyogo in Honshu are highly infested (Kosaka et al., 1955). It is significant that Babero and Shepperson (1958) found G. spinigerum from raccoons in Georgia, U. S. A. Their report is too simple to be compared with Asian specimens, but, if their identification was correct, this finding might be the first in the new continent. Most recently, however, Dr. L. R. Ash informed me that he compared the specimens of Babero’s G. spinigerum with G. procyonis and with Japanese G. spinigerum which the author gave him, and he came to the conclusion that Babero’s specimens were not spinigerum, but procyonis. 2. Morphological

Features of the Adult Worms

The structure of the adults, measuring 2-3 cm in length, was described by Owen (1836), Leiper (1909), Baylis and Lane (1920) I Miyazaki (1954a), etc. Recently, Takeichl (1956) gave detailed descriptions, illustrating them with as many as 47 text figures and 12 phot,omicrographs. The cuticular spines, which are, as already mentioned, good criteria of distinction, extend from immediately behind the head-bulb to almost the middle of the body, the posterior half being naked except at the terminal (Fig. 2). In the female, minute spines are arranged densely in many transverse rows on the terminal, especially on its ventral surface (Fig. 2, T). This character, not yet described by any earlier investigators, was reported by Miyszaki and Umetani (1951b) and Miyazaki (195213, 1954a). In the male, the ventral surface of terminal is also provided with numerous minute spines. In this spinous surface there is a Y-shaped naked area around the cloaca1 aperture, behind which some minute spines are seen arranged in a few arched lines (Fig. 3, L). This T-shaped naked area was previously described by Baylis and Lane (1920), but the arched spinous lines were overlooked by them. The left spicule varies 0.9-2.1 mm and the right one measures 0.4-0.5 mm in length. The cuticular spines vary in shape with their position on the body; the spines immediately behind the head-bulb (Fig. 2, A), small in number, are broad and short with

I

/

l-

FIG. 2. Extent and shape of cuticular of a female G. spinigerum. T: Ventral view terminal end.

FIG.

male

3. Ventral view of the terminal G. spinigerunt (spicules omitted). 1-4: Large pedunculate papillae A-D: Small ventral papillae K: Cloaca1 aperture L: Spinous arched lines

spines of the

end

of a

342

MIYAZAKI

FIG. 4. Fertilized uterine egg of G. containing an unsegmented ovum.

spimiyerum

several teeth, and gradually increasing in length, are transformed into three-t,eet,hed spines. These spines (B), most numerous and most useful in differentiation, have linear margins and three teeth, of which the middle one is generally somewhat longer than either of the two lateral ones. The spines gradually decrease posteriorly in size and density, as well as in the number of their teeth (C, D), and finally disappear on the middle part of the body. Fertilized uterine eggs (Pig. 4) are colorless and have each an unsegmented ovum, their shellshaving a fine granulation on their surface and a cap-like thickening on their one pole. In feces of t,he final host, however, they are stained from yellow to brown containing each an ovum in one or two segments. They measure 79-62 X 42-36 p, averaging 69.3 X 38.5 /A. 3. Life History After the discovery of G. spinigerum about 100 years had passed without clarifying its life history, except that Chandler (1925b) found a lot of encysted larvae from snakes in India and presumed them to belong to G. spinigerum, discussingits life history and except that Heydon (1929) observed the hatching of larvae from eggs, which were obtained from an infected cat and kept in water. A real study of the life history was begun by Prommas and Daengsvang (1933, 1936, 1937) in Thailand. They found out experimentally that the first intermediate host was cvclons ” .

and

t,he second

one was t,wn kinds

of fresh-water fish, Clarias batrachus and Ophicephalus striatus. Then Daengsvang and Tansurat (1938) disclosed the natural infection with gnathostome larvae (presumably of G. spinigerum) in frogs (Rana rugulosa), eels (Monopterus albus), 0. striatus and C. batrachus. Meanwhile, Africa, Refuerzo and Garcia (1936a, b) of the Philippines reported the occurrence of encysted gnathostome larvae in three species of fresh-water fish, i.e. in Glossogobius giurus, 0. striatus and Therapon argenteus, as well as in an aquatic snake, Hurria rhynchops, thus contributing to the study of the life history of G. spinigerum. In addition, Refuerzo and Garcia (1938) studied in detail the first intermediate host, cyclops, and the pre- and intra-crustacean development of the larvae. In Japan, twenty years later, Miyazaki and Umet)ani (195la, b), Umet’ani (1949, 1951), Miyazaki (1952a, b, c, 1954a, b), Isobe, H. (1952a, b), Sagara (1953), Miynzaki and Kikuchi (1954a), Kikuchi (1956) and Ueki (1957) carried out experiment,al studies on the life hist’ory of this nemat,ode and obtained the following new resuhs of interest. Fertilized eggspassedfrom the final hosts, commonly cats and dogs in Japan, usually contain one or two cells. When they are kept in water at 27”C, the first stage larvae enveloped in a delicate sheath become mature after 5 days and begin to hatch after 7 days. The ensheathed larvae, measuring nearly 0.3 mm in length and swimming ceaselessly in the water, are finally ingested by the first intermediat’e host. Four species of cyclops, Mesocyclops leuckarti, Eucyclops serrulatus, Cyclops strenuus and (1. vicinus, were experimentally determined as the host. The larvae swallowed by oyclops cast off their sheath, pierce the gastric wall of the host and enter into body cavity to develop into mature second stage larvae in 7 to 10 days after ingestion. In the host body the larvae cast off their skin once more and grow to 0.5 mm in length (Fig. 5). But there are somelarvae which

degenerate

in

the

body

cavity

of

cyclops. The mature larva is covered with minute cuticular spines all over the body and has t,he head-bulb provided with four

HUMAN

343

GNATHOSTOMIhSIS

are significant t,o differentiate this species from the others (Fig. 15). When a crustacean host harboring mature larvae is swallowed by a second intermediate host, the larvae pierce the gastric ~a11of the latter and enter mainly into it,s muscle, where they mature to t’he third stage larvae in a month or more, growing to about 4 mm in lengt’h. They finally become coiled like a snake, and become encyst’ed in a fibrous membrane, the diameter of t,he cyst measuring about 1 mm (ITig. 6). This course of infection is called “primary infect,ion” of the second intermediate host. Experimentally, three species of fresh-wat,er fish, Ophicephalus argus, Nogurnda obscura and Misgurnus were subjected to this anguillicaudatus, “primary infection” \vit,h posit,ive results. Another course is called t,he “secondary infection” of the second imermediate host, which means the infection of the host wit,h third stage larvae encyst,ed in ot,her second iluermediate hosts. This course of infection seemst,o be prevalent, in the natural world. lip to this time the following 33 animals, experimentally fed with the third stage larvae, have all been found to be infected through the course of “secondary infection”: three crustaceans including Procambarus clad%, Erioch& japonicus and I’otaeight, fishes including Ophimon dehaani; wphalus anglLilliCauclatuS,

FIG. 5. spinigerurn.

Lat,eral

view

of a second

larva

argus, A nguilla

japonica,

~‘cmLdUrll~S

3f isgurn us QSOfllS,

c!J-

of G.

I, : Lip H : Head bulb 0 : Esophaglls C: Cervical sac I: Int,estine (2: Genital primordium A: Anus

rows of hooklets, the average numbers of which are 43.2 on the first, 44.8 on the second, 46.7 on the third and 52.3 on the last row, increasing posteriorly. These numbers

FIN;. 6. Third stage larva of G. spinigerum encysted in the flesh of n fish, Ophicephalus argus.

344

MIYAZAKI

prinus auratus, C. carpio, Acanthogobius $avimanus and Japanese goldfish; eight amphibians including Rana nigromaculata, R. catesbiana, R. rugosa, R. limnocharis, Hyla arborea japonica, Bufo vulgaris formosus, Hynobius naevius and Triturus pyrrhogaster; five reptiles including Geoclemys reeve&i, Elaphe quadrivirgata, Natrix tigrina

FIG.

7.

tigrina, Takydromus tachydromoides and Gecko japonicus; three birds including Gallus gallus domesticus, Nycticorax nycticorax and Gorsachius goisagi; six mammals including Rattus norvegicus var. albinus, Mus bactrianus albula, Oryctolagus cuniculus var. domesticus, Cavia cobaya, Mustela sibirica itatsi and Xus scrofa var. domesticus.

Third stage larva of G. spinigerum. 1. Lateral view of the whole body. L: Lip H: Head bulb P: Cervical papilla E: Excretory pore C: Cervical sac 0: Esophagus I: Intestine V: Vulva G: Lateral line A: Anus 2. Lateral view of a hooklet on the head bulb. 3. Dorsal view of the same one. 4. Cuticular spines on the anterior extremity of the body.

HUMAS

GSATH~~T~MIASIS

The same third stage larva can be parasitic in one after another of the above mentioned animals without making any morphological development except a slight increase in length and in color while in warm-blooded animals. The morphology of this larva is illustrated in Fig. 7. The head-bulb is provided with four transverse rows of hooklets, of which the number and shape are very useful for identification of this species. The number of the hooklets on each row is usually over forty in almost all specimens and gradually increases posteriorly, averaging 44.3, 47.3: 49.6 and 52.0, respectively. These are features almost equally observable in the second stage larvae of the same species. The hooklets have each an oblong base and are almost equal in size, except that those of the first and the last row are somewhat smaller than the others (Fig. 8). The whole larval body is also covered with over 200 transverse rows of single pointed spines, which are 10 p in length and arranged closely on the anterior part of the body, but gradually reduced in size and density towards the posterior extremity, where they measure about 2 p in length. These minute spines on the posterior part of the body have been overlooked by prior investigators: In tropical regions Chandler (1925b), Prommas and Daengsvang (1936) and Daengsvang and Tansurat (1938) reported the absence of cuticular spines on the posterior half of the larval body of G. spinigerum. Miyazaki (1955) pointed out their error of investigation by examining the larval specimens brought from Bangkok, Thailand. The internal structure of the larvae was most exactly described by Morita (1955). Out of his findings the following ones are noteworthy: 1) The cervical sacs, four muscular tubes, are each opened into respective ballonets in the head-bulb, being filled with somewhat muddy liquid. These systems, four in number, seem to play an important role in swelling and contracting the head-bulb. 2) The esophagus is divided into the muscular and glandular portions. The latter-the esophageal gland-is further divided into the dorsal gland and two subventral glands, their ducts being opened near the anterior margin of the glandular portion into t,he

345

esophageal lumen. The nature of the dorsal and the subventral glands seem to be different from each other. 3) The larva contains the blood-red coelomic fluid and this color is much deeper in the larvae parasitic in warmblooded animals than in those in coldblooded ones. The tone of this color comes fro+m oxyhemoglobin retained in solution. When second intermediate hosts, widely distributed among wild and domestic animals, are eaten by the final host, the third stage larvae penetrate the gastric or rarely the intestinal wall of the final host, and entering into the liver and thence wandering t’hrough the muscle or connective t’issue, grow gradually in size there. After they are almost matured, the worms enter into the gastric wall of the hosts from outside and make there the characteristic t,umor, the

FIG. 8. Comparison between head bulbs of the ;hird stage larvae of G. spinioerum. (upper) and 2. dolores?;.

346

MIYAZAKI

Philippines, Wharton (1918) reported that out of 118 dogs examined 8 were infected with G. spinigerum, and Africa et al. (1936a) found the same adult gnathostomes in typical nodules in the stomach wall and immature worms in the liver of 2 cats out of 6 autopsied. They also found the same immature worms in the liver of 2 of 7 dogs examined. According to Morishita and Faust (1925)) 1 of 85 dogs and 2 of 58 cats in China were found to be infected with the same gnathostome. Andrews (1937) found it in the stomach of 4 dogs (0.68%) and 7 cats (3.78%) in Shanghai. Komaya, Kitamura FIG. 9. Diagrammatic representation of adults and Komiya (1945a) reported that in the of G. spinigerum parasitic in a gastric tumor of a same district 7 of 178 cats and 2 of 213 dogs cat. Eggs emergethrough a small aperture (ar- harbored it in their gastric t,umors. row). In Japan, Miyazaki and Isobe, H. (195la, b), Isobe, H. (1952a) and Miyazaki (1954a) number of which per host is usually one, continued the survey of cats and dogs by rarely two or more. The typical tumor has a post-mortem examination in the endemic cavern, which communicates with the stom- areas of Fukuoka and Saga Prefectures, ach lumen through a small aperture (Fig. Kyushu; and it was proved that 14 of 51 9). The adult worms are parasitic in the cats harbored 48 mature worms (28 females, cavern, putting their fore-body into thick20 males) in their gastric walls and 21 imened stomach wall, and the eggs flow out mature worms principally in their livers, the through the small aperture. The eggs of the maximum number of worms per host worm appear in the feces of the host in 100 amounting to 22. Of 643 dogs examined, 26 days or more after infection. were found to be infected with 41 worms in all, including 18 females, 13 males and 10 4. Natural Infection of’ the Final Host immature ones; the maximum number of The common host of G. spinigerum is the worms per host was only 5 in t,hesecases. cat and the dog. In India, Mitter (1912) These investigations, the first of the kind found the worm in a cat, a dog, and a in Japan, were followed by Okabe and his leopard, and Chandler (1925a) reported t’hat co-workers (1952) in the same locality of on t>he post-mortem examination of cats, Kyushu. They reported that 13 of 90 cats about 10 to 30% were found t,o be infected and 2 of 365 dogs were infected with the with this worm. In Australia, Heydon same worm. Isobe, C. (1956) autopsied 131 (1929) found that, in about 40 cats and dogs and 34 cats in Kumamato Prefecture, kittens in Townsville, in which the stom- Kyushu and found 6 of t)he former and 3 of ach was examined, G. spinigerum was pres- the latter were infect,ed with the worm. In ent in one inst,ance. This infect,ed cat was Shikoku, Irie (1958) reported that on the an adult female harboring 19 male worms post-mortem examination of 632 dogs and 83 and 30 females in its single stomach tumor. cats in Kagawa Prefecture, 11 dogs and 6 In Thailand, Prommas and Daengsvang cats were found to be infected with G. (1933) examined the stool of cats for spinigerum, respectively. In Honshu, Tognathostome eggs and found that 9 of 24 shida et al. (1936) found, as already menanimals were positive, one of which was sac- tioned, unexpectedly 7 adult G. spinigerum rificed to confirm the diagnosis and on in 2 cats in Osaka Prefecture. autopsy revealed 10 adult G. spinigerum in On the other hand, Miyazaki (1952b, its stomach tumor. In addition they exam- 195413)examined the feces of tigers and ined stomachs of 5 dogs and all were found leopards collected from several zoological to be infected with the same worm. In the gardens in Kyushu and Honshu, and found

HUMAS

GS.ATHOSTOMIASIS

347

Miyazaki and Umetani (1950b), Umetani and Arita (1951), Umetani (1951), Miyazaki and Nagao (1952, 1953), Miyazaki, Kamo and Kikuchi (1953), Arita (1953), Ijima (1954, Miyazaki (1954b), Nagao (1956b), Isobe, C. (195G), Jhmaguchi et al. (1955a, b), Otsuru et al. (19X), Irie (1958): Kat,amine and Baieda (1958)) and Kat agirl (1939). It’ was clarified, as shown in Table II, that 32 animals including eight’ species of Pisces,t,wo speciesof Amphibia, three species 6. &Yatural Infection of the Second of Reptilia, 18 speciesof AWR and one speries Intermediate Host of df ammalia were nat,urally infected wit,h As stated above, Daengsvang and Tan- larval G. spinigerum, which was mainly surat (1938) in Thailand reported that, 11 of parasitic in the muscle of these hosts. Of 12 frogs (Rana rugulosa), 8 of 10 eels these naturally infected animals, Ophiceph(Monopterus albus), 15 of 40 Ophicephalus alus argus, 0. tadianus, Acanthogobius hasta, striates and 6 of 20 Clarias batrachus were Cyprinus auratus and Gallus gallus domesnaturally infected wit)h the larvae of G. ticus are significant as t,he vector of the spinigerum. According to Daengsvang (1949) human gnathostomiasis in Japan, because 19% of Ophiccphalus micropeltes, 11 % of their raw flesh is frequently eaten by Notopterus chitala, 5% of Anabas testu- Japanese people. dineus, 3 % of Trichopodus trichopterus, 2 % CTNATHOSTOMA DOLORESI Tubangui, 1925 of T. pectoralis and Cryptopcrus apongon, and all of t,he fresh-water snakes examined This worm was first found by Tubangui were naturally infected with the samelarvae. (1925) in the gastric wall of a pig in Luzon, In 1957, about, 20 years later, the author t,he Philippines, but his description n-as had a chance t)o examine two kinds of fresh- based on only four female specimens,lacking water fish bought at a market in Bangkok, male ones. Naplestone (1930) described the Thailand, and found the larval G. spinigewm male from India, where he found this species in six of eight, 0. striatus and one of three in the stomach of 11 pigs out of 49. C. batrachlts. According t’o Africa et al. Twenty years later, Jliyazaki (1950) es(1936a) in the Philippines, three speciesof amined t,he old preserved specimens, which fresh-mater fish and a kind of aquatic snake had been obtained from two pigs slaughtered were found t,o be naturally infect,ed with t,he in Tokyo and labeled as G. hispidum, and samelarvae; i.e. all of 11 Glossogobiusgiurus, he identified them with G. doloresi. This was tsvo of eight, 0. striatus, three of 23 Therapon the first finding of this nematode in ,Japan. a,rgenteusand all of six Hurria rhynchops Then Xyaznki, Arita, and Isobe, H. (1951) were positive for the larvae. In China, and Miyazaki, Ishii, and Isobe, C. (1953) Komayn, Kit)amura, and Komiya (1945b) found the same gnathostome abundantly in examined six species of fresh-water fish for wild boars, Sus scrqfa leucomystax in Kyushu. larval G. spinigerum, which were bought, at Morishita (1951), who also re-examined the a mark& in Shanghai, and obtained the old specimensfrom pigs, which he previously following results: 106 of 200 0. argus, 23 of identified wit’h G. hispidztm, recognized them 110 Siniperca chautsui, 33 of 100 Mogurnda afresh as G. doloresi. Sandosham (1953) idenobscura and 3 of 100 Pelteobagrusfulvidraco tified the specimens with G. doloresi, which mere positive for the larvae, but 42 Cyprinus were obtained from t’he liver of a pig in carpio and 27 Carassius auratus were all Singapore. Recently, Miyaznki (1957) found negative. the eggs of this nematode in feces of a mild In Japan, many kinds of animals were boar that had come from Okinawa, and Chiu examined for the third stage larvae mainly (1959) in Taiwan found 12 specimensof this by the members of the above-mentioned co- worm in t)he stomach wall of a wild boar, operatirc research group, particularly by Sirs 1eiicomysta.t tailanus. gnathostome eggsin 2 of 8 tigers and in 5 of 12 leopards. These eggs were used for the study of life history and the adults experimentally obtained were identified with G. spilzigerum. Of these 7 cnrnivora infected, 1 t’iger and 4 leopards had been imported from Thailand and the other two from ;Ilalaya. Shirakawa (1959) clarified experimentally that the fox, Vulpes vwlpesjaponica could be a final host of G. spinigerum.

348

MIYAZAKI

TABLE Natural

Name

Infection

of 32 Animals

II with

Larval

No. hosts examined

of host

G. spinigerum Max.

No. hosts infected

No. Locality

larVh:tPe -

-

Pisces

Amphibia

Ophicephalus argus 0. tadianus Parasilurus asotus Misgurnus anguillicaudatus Mogurnda obscura Anguilla japonica Acanthogobius hasta Cyprinus auratus 1

Rana nigromaculata R. catesbiana

--

-.

Elaphe

1246 111 48 291 95 33 94 104 193 40

quadrivirgata tigrina tigrina orientale

4 9 1

Aves

Nycticorax nycticorax Ardea cinerea jouyi Egretta garzetta garzetta Podiceps ruficollis poggei Mergus serrator Anas crecca crecca A. platyrhynchos domestica Alcedo atthis bengalensis Rallus aquaticus indicus Pica pica japonica Corvus corone corone C. coronoides hondoensis Scolopax rusticola Gallus gallus domesticus Strix uralensis juscescens Milvus migrans lineatus Pandion haliaetus haliaetus Accipiter gentilis fujiyamae

36 3 1 26 2 1 2 3 45 30 12 4 2 14 3 4 1 1

Mammalia

Mustela

Reptilia

Nat&x Dinodon

sibirica

--

itatsi

-

---

1. Geographical Distribution As mentioned above, this nematode was found in pigs in India, Singapore, Philippines and Japan, as well as in wild boars in Taiwan, Okinawa and Japan, showing a wide distribution in Asia. In Japan, by the members of the co-operative research group, as well as Ono et al. (1957) and Yokogawa et al. (1959) a lot of wild boars were examined for this nematode in almost all prefectures

154 2 7 2 1 7 1 1

Kyushu Honshu Kyushu Kyushu Kyushu Kyushu Kyushu Shikoku

10 6

2 10

Kyushu Kyushu

1 8 1

1 7 10

Kuyshu Shikoku Shikoku

35 3 1 20 1 1 1 1 6 13 5 2 1 4 1 4 1 1

36 18 8 7 3 1 4 1 2 6 5 2 1 6 2 187 201 24

Kyushu Kyushu Kyushu Kyushu Kyushu Shikoku Kyushu Kyushu Kyushu Kyushu Kyushu Kyushu Kyushu Shikoku Kyushu Shikoku Shikoku Shikoku

13

Kyushu

--

--

430

-

1002 16 12 21 4 10 1 1

.-

69

-

-

where they live, and as shown in Fig. 10, the worm was proved to be widely and densely distributed among wild boars, particularly among those of Kyushu and Shikoku. By the way, this mammal does not live in the northern half of Honshu. 2. Morphological

Features of the Adult Worms

Because the illustrations of the worm by Tubangui (1925) or Maplestone (1930) were

HUMAN

GNATHOSTOMIASIS

FIG. 10. Distribution of G. doloresi in Japan. Solid black prefectures the worm. Denominator: Number of wild boars examined Numerator: Number of wild boars infected

fragmentary, Miyazaki (1950,1954a) figured its morphological features in detail (Figs. 11 and 12) ; afterwards Ishii (1956) added some features to the author’s illustration. The nematode is covered with cuticular spines all over the body. This is the reason why the present worm was frequently confused with G. hispidum; on the contrary, this is a remarkable character, making the worm very easily distinguishable from the other two species in Japan. The anterior half of the body is covered, like that of the other two, with spines provided with two to several teeth; the posterior half is, however, densely covered with single-pointed spines (Fig. 11, D) gradually decreasing in length posteriorly. The cuticle of this single-pointed area is loosely connected with the subcuticle, so that it swells easily in mature worms and becomeswavy in immature ones, when they are preserved in liquid. In the male the body terminal has a roundish or oval spineless

are infested with

area on it’s ventral surface around the cloaca1 aperture and on the ventral side of the tail end (Fig. 12). The spinesof G. doloresi resemblethose of G. spinigerum in shape, but are generally more slender than the latter; the most important of the former spines (B) are particularly slender and their middle tooth is conspicuously longer than the lateral ones. Fertilized uterine eggs (Fig. 11) have very fine granulation on their shells; they are colorless and contain unsegmented ova, but in feces they are stained from yellow to brown, containing ova usually in one or two segments. The eggs are provided with two caps at either end of their shells; this is a distinct character to differentiate G. doloresi from the other species especially from G. hispidum. The eggs of doloresi, smaller than those of the others, measure 62-56 X 35-31 II, averaging 58.7 X 33.3 pcL.

350

MIYAZAKI

FIG.

uterine

11. Extent and shape of cuticular spines of a female G. egg containing an unsegmented ovum.

3. List?Hisfory This problem had been entirely unsolved, till Miyazaki and Ishii (1952a, b) discovered the second intermediate host of this worm. The natural final host of this nematode is, as mentioned above, pigs and wild boars, and in Japan the latter is far more significant. Among Japanese pigs the incidence of infection with this worm is very low: At Fukuoka Slaughter-house 306 pigs were examined post-mortem, but no positJive result was obtained; in Kumamot,o Prefecture, Tsobe, C.

doloresi,

and a fertilized

(1959) examined 88 pigs and found only one female worm from the gastric wall of one pig. The adult worms are parasitic in the gastric wall singly or in groups, stretching out their hind bodies into the gastric cavity (Fig. 13). The gastric wall around the parasites is gradually thickened, so that, when they are taken off their burrows, it leaves a crater-like depression. Besides mature worms, immature ones are frequently recognized in the gastric mall, hiding their -whole hodv.

HUMAX

FIG.

12.

Ventral

view

of the

GNATHOSTOMIASIS

terminal

l-4: .4-l) : K : T: S:

end of a male

G. dotoresi

(left

spicule

broken).

Large pedunculate papillae Small vent,ral papi1la.e Cloaca1 spert,ure Tail end Right spicule

When fertilized eggs of the worm passed from boars are kept in water at 27”C, the ensheathed first stage larvae develop in eggs in 5 days and begin to hatch in 7 days to be ingested sooner or later by the first. intermediate hosts, Mesocyclops leuclcarfi, Eucyclops serrulatus, Cyclops strenuus, and C. vicinus. The ingested larvae excyst in the intest,ine and enter into the body cavity of these crustacean hosts and develop into mature second stage larvae after 7 days at the same temperature. These pre- and intracrustacean development of the larvae were exactly studied by Ishii (1956). According to him the second ecdysis of the larvae occurs in the body cavity of cyclops and it is characterisGc t]hat prior to ecdysis the frontal end Df the larval body is transparent, expanded and protruded anteriorly on one side. The

FIG. 13. Diagrammatic adults of G. doloresi parasitic of a wild boar.

representation in the stomach

of wall

352

MIYAZAKI

infected copepods were experimentally given to a number of fish, amphibia, and reptiles, in which, however, none of the developed larvae mere found. Meanwhile, Miyazaki and Ishii (1952a) found a new larval gnathostome encysted in the muscle of the salamander belonging to the genus Hynobius (Fig. 14). The larvae were experimentally proved to develop into adult G. doloresi in the gastric wall of a wild boar as well as that of a pig. Some fertilized eggs mere obtained from feces of the boar in 5 months and from those of the pig in 3 months after experimental feeding. Ishii (1956) examined 342 of Hynobius naevius and 28 of H. stejnegeri captured in Kyushu, and proved that 30 (8.8%) of the former and 1 (i3.5 %) of the latter were infected with the larval G. doloresi, the number of which found per host was eight at the maximum in the former and only one in the latter. Miyazaki (1952c, 1954b) studied the morphology of the second stage larvae, comparing those of G. doloresi with those of G. spinigerum and nipponicum: The larvae of doloresi have almost the same structure as the other two, but are much smaller than the others, measuring 338-260 P (averaging 315 P) in length. The head-bulb of the larva is provided with 4 transverse rows of hooklets like G. spinigerum, but the numbers of hooklets on each row do not so much vary as spinigerum, averaging 37.6, 37.9, 36.5, 37.0 posteriorly. They do not usually amount to 40 and the hooklets of the last row are, as a rule, fewer than those of the first. The hook-

FIG. doloresi Hynobius

14. Encysted third stage larva of G. removed from the muscle of a salamander, naeuius.

FIG. 15. Comparison of head bulbs of the (upper), G. second stage larvae of G. spinigerum doloresi (middle), and G. nipponicum.

lets are almost equal in size in G. spinigerum and nipponicum, but in G. doloresi they are larger posteriorly, so that those of the first row are conspicuously smaller than those of the last one (Fig. 15). These characteristics are significant to differentiate G. doloresi from the other two. The third stage larva of G. doloresi was described by Miyazaki and Ishii (1952a) and Miyazaki (1954b). Although the structure of this larva is almost similar to that of G. spinigerum, there are many differences between the two (Fig. 16). The present larva is a little more than 3 mm long and 0.3 mm wide, presenting a stumpy appearance. Except the intestine, which is light brown, the body is colorless, because it has no colored

HUMAS

GXATHOSTORII.~SIS

353

liquid in the body cavity. The head-bulb is provided with four rows of hooklets as in G. spinigerum, but each row, almost wit’hout exception, has less than 40 hooklet’s, t’he number of which is smaller in t’he fourth row t’han in the first one, posteriorly amounting to 35.7, 35.7, 33.4, 33.8 on the average. The hooklets have each a roundish or irregularly square base and are conspicuously small in size in the first row (Fig. 8). These features are good criteria in distinguishing G. doloresi from spinigewm or nipporkum. GNATHOSTOMA

KIPPONICUM

Yamaguti,

1941

Over 25 years ago, Yoshida (19:31, 1934a, b) reported an interesting result of his extensive survey, namely that out of 6565 Japanese weasels, Mustela sibirica itatsi caught in Kansai district of Honshu, 2869 (43.7 %) were found infected wit’h adult, gnathostomes, which he called erroneously G. spinigerum. Afterwards Yamaguti (1941) also obtained someadult gnathostomes from the same host in the same locality and he named it G. nipponicum n. sp. About 10 years ago, Miyazaki and Umetani (195Oa) found 39 worms from 18 weaselsout of 259 captured in Saga Prefecture, Kyushu and identified them with G. nipponicum. Since then, abundant weaselshave been examined for gnathostomes almost in every prefecture in Japan. The adult gnathost’omesobtained were all identified with nipponicum, not, a single specimen of adult spinigerum having been found from the weaselsexamined. Consequently, the Japanese weasel must be omitted from the list of t,he final host of G. spinigerum. By the way, the lveasel is, as stated above, the second intermediat,e host of spinigerum. The geographical distribution of G. nipponicum in Japan is shown in Fig. 17, together with the respective numbers of weaselsexamined and those of infected with the worm. There has so far been no report of this gnathostome outside our country.

FIG. 16. Lateral view of a third stage larva of G. doloresi. L: Lip H: Head bulb I’: Cervical papilla C: Cervical sac 0: Esophagus I: Intestine G: Lateral line A: Anus.

single worm was found parasitic in the gastric wall, the common habitat of the genus Gnathostoma. This is one of the characteristics of G. nipponicum. 1. Morphological Features of the Adult Worms Concerning the morphology, Yamaguti The present nematode is wholly parasit,ic (1941) described it in detail for the first time, in the esophageal wall of the Japanese pointing out the differences between this and weasel, making there usually one hard tu- G. spinigerum in the ventral surface of mor, in which the ossification is frequently terminal of the male body as well as in the recognizable (Fig. 18). On the contrary, not a size and contents of the egg. hlliyazaki and

354

MIYAZAKI

FIG. 17. Distribution with the worm.

of G. nipponicum Denominator: Numerator:

in Japan. Solid black prefectures

Number Number

Umetani (1950a) agreed to ‘l-amaguti’s view regarding the terminal of the male body and the size of the egg, but did not as to its contents and besides they pointed out the character of cuticular spines. Miyazaki (1954a) illustrated these features in detail in his later paper. The adult G. nipponiucm is generally similar t’o G. spinigerum in the extent of cuticular spines, except the terminal end of the body. The posterior half of the female body is entirely naked, with no spines visible at its terminal end (Fig. 19). The male body has numerous minute spines densely arranged on its terminal, apparently resembling that of G. spinigerum, but there is no Y-shaped naked area around the cloaca1 aperture (Fig. 20). In the shape of cuticular spines the present species differs distinctly from G. spinigerum. The three-teethed spines (B in Fig. 19), the most marked features, have margins slightly convexed and terminally increasing in breadth. Of their three teeth, the middle one is much longer than either of t,he lateral two. The spines, as they extend downwards, becomegradually smaller

are infested

of weasels examined of weasels infected

and shorter, diminishing their teeth in number and in length, dwindle into singletoothed minute spinesand finally disappear. The convexity of the lateral margins, which is one of the characters of this species, is kept visible in the single-toothed spinesalso. The fertilized eggs of G. nipponicum have the same appearance as those of G. spinigerum: They are originally colorless and have unsegmented ova, but in feces of the final hosts they are stained from yellow to brown, containing ova in one or two segments; the shells have a very fine granulation on their entire surface and a cap-like thickening on their one pole. Therefore, the eggs of these two species are not always easily differentiated from each other, but those of G. nipponicum are a little larger than the other, measuring 76-69 X 45-39 (averaging 72.3 X 42.1) CL. 6. Life History Yoshida (1934a,b) and Yoshida etal. (1936) first st’udied the life history of G. nipponicum, which, however, he called G. spinige-

HCMAS

G~ATHOSTOMLC3IS

rum. After he revealed that the first. imermediate host of this worm was cyclops, he tried to disclose further development of the worm. However, his study n-as discontinued n-it’hout getting any marked result. About, 20 years later, Miyazaki (1952c, 1954b) and Arita (1953) again studied this problem. The development of the larvae in eggs and in t,he first intermediate host’ is almost t.he same as t)hat of G. spinigerum or doloresi. Three species of copepods, JIesocyclops leuckarti, Eucyclops serrulatus and Cyclops uicinus, were proved by experiment, t,o be the first intermediate host of t’his nematode. Pre- and intra-crustacean development of the larvae was investigated by Arita (1953), who found that t’hc second ecdysis of t,he larvae occurred near the end of t,heir development. This investigation was followed by hlabuchi (1957), and more detailed description was added concerning intra-crustacean development of t,he larvae. In order to determine the second intermediate host,, Arita fed several species of fish and amphibia with copepods containing mature second stage larvae of t,he nematode, and obtained from frogs a few somewhat advanced larvae. Accordingly, he investigated t,he natural infection of frogs with negative result. Anyway, the secondint,ermediat’e host of G. nipponicum remains unsettled. The body of mature second stage larvae of t’he nematode are generally longer t)han spinigerum or doloresi, measuring 577 p on the average. The whole body is covered with many transverse rows of minute spines. The head-bulb (Pig. 15) is provided with t,hree rows of hooklet#s, t,he number of which is usually less than 40, slightly increasing post,eriorly. Sometimes, t,here is t,he fourth row, which makes a complete or incomp1et.e ring. Because the third stage larva of G. nipponicum has yet been obtfained in mature form neither by experiment’ nor in the natural world, there is no specimen of it, available for detailed comparison with that of spinigerum or doloresi. But it is presumable from the features of the above-mentioned immature larvae that the characters of t,he head-bulb of the second stage larva will be seen unaltered in the third stage and t)hat t#he hooklets will ayuire some characteristic shape in mature form.

FIG. 18. IXagrammatic representation of adults of G. nipponicunl parasitic in an esophageal tumor of a weasel. GKATHOSTOMA

HISPIDUM Fed&e&o, 1872

According to Baylis and Lane (1920), this nematode was found by Fedchenko (1872) from the gastric wall of a wild pig of Turkestan and a domestic pig of Hungary. Aft*erwards, Csokor (1882) obtained this worm from domestic pigs in Wien, Strose (1892) from pigs in Gottingen, which were imported from Hungary, and Ciurea (1911) from Roumanian pigs. Meanwhile, Collin (1893) found t’his gnathostome in the fat of an ox in Berlin. In Asia, Chen (1936) reported that six of 100 pigs slaughtered in Canton, China were infected with G. hispidum. According to Tubangui (1947) and Sandosham (1949)) this nematode was also recorded in the Philippines and Malaya, respect’ively. Miyazaki (1955) had a chance to investigate 3

356

MIYAZAKI

FIG.

19.

Extent

and

shape

of cuticular

females of this nematode obtained from a pig in Shanghai, China, and he illustrated the features of cuticular spines (Fig. 21). Recently, Chiu (1959) in Taiwan re-examined the specimens which had been deposited in the College of Agriculture, National Taiwan University, with the label of “G. hispidum, Taipei, 1914-1917, swine stomach,” and he re-confirmed them as hispidum. In Japan, on the other hand, some specimens of this gnathostome had been

spines

of a female

G. nipponicum

reported from pigs and wild boars (Mizumura et al., 1940), but,, as mentioned above, they were recently proved to be G. doloresi. Insofar as the author is aware, G. hispidum has not yet been found in this country. From the medical point of view, G. hispidum is somewhat significant, because two cases of human gnathostomiasis were reported to be caused by this nematode. Morishita (1924) identified a young female specimen as G. hispidum, which was extir-

HUMAN

FIG.

20.

Ventral

view

of the terminal 14: A-D: K: T:

end of a male

G. nipponicum

(spicules

omitted)

Large pedunculate papillae Small ventral papillae Cloaca1 aperture Tail end

pated from a male Japanese in Tokyo and lacked the head-bulb as well as the anterior part of the body. Chen (1949) obtained an immature specimen from the eye of a male Chinese in Canton and tentatively assigned it to G. h&pi&m. The identification of these authors is chiefly based on the presence of cuticular spines on the entire body of the worms obtained. However, this is not a good criterion, because it was proved that immature specimens of both G. spinigerum and doloresi were also covered with spines to the ends of their bodies. Consequently, the author is very skeptical about t’he identification of Morishita and Chen. I. Morphological

357

GNATHOSTOMIASIS

Features of the Adult Worms

The head-bulb is provided with over 10 rows of hooks, and the body is entirely covered with cuticular spines. The spines at the anterior extremity are small, having several teeth (Fig. 21, A), but they posteriorly increase in size and in number of teeth. After the teeth reach to about ten in

number, they rapidly diminish, increasing in length terminally (B, C), and finally become single (D). These one-toothed spines cover most of the worm body, and the threetoothed ones, which are useful in distinguishing G. spinigerum, doloresi, and nipponicum, are scanty in number and less useful in the present species. Anyway, adult G. hispidum is easily confused with doloresi because of the presence of their spines all over the body, but they can be clearly distinguished from each other by t’he shape of their spines and bheir fertilized eggs. The egg of hispidum looks like that of spinigerum, being provided with a cap at one pole, but is a little larger in size, measuring 72 X 40 p on the average and the granulation of its shell is more evident than the latter. 2. Life History According t)o Helminthological Abstracts, Vol. 25, Part 5, Golovin (1956) studied the biology of G. hispidum, and the results of his work, mrit,ten in Russian were sum-

MIYAZAKI GXATHOSTOMA

PHOCYONIS Chandler, 1942

This nematode was discovered by Chandler (1942) in the stomach of 10 of 13 raccoons, l’rocyon lotor lotor, captured in Texas, ‘c’. S. A. Recently, Babero and Shepperson (1958) and Jordan and Hayes (1959) also found the same worm from raccoons in Georgia. Last year the author heard from Dr. L. R. Ash of Tulane University that the worm was also parasitic in the same host in the vicinity of Kew Orleans, Louisiana. 1. Morphological Features of the Adult Worms

FIG. 21. Extent and shape of cuticular of a female G. hispidum.

spines

marized as follows: Eggs hatched after 9 to 10 days at 25°C or 15 days at 18°C. The larvae could survive for 20 to 30 days in water at 22°C. The ten species of Cyclopidae (not named) tested all became infected. The first two molt’s occurred in the egg, the third and fourth in the cyclops. Larvae in the cyclops become infective after 17 days at 18°C and 7 days at 27°C. The infective larva is 0.488 to 0.520 mm long, has small spines anteriorly and the head swelling carries four rows of small hooks. The esophagus is 0.22 mm long. The final host becomes infected either by drinking water containing the infected cyclops or by eating flesh of the reservoir hosts, e.g. fish, a,mphibians or reptiles etc.

By the courtesy of the late Prof. Chandler, the author had an opportunity to investigate some specimens of this nematode, and illustrated the features of its cuticular spines in his paper (1955). As shown in Fig. 22, the present worm resemblesG. spinigerum in the shape of spines on the anterior half of the body, but in the appearance of the posterior half, they are quite different; namely, the present worm is provided with numerous transverse serrations till the end of the body (D), but spinigerum is naked, except the spineson the posterior extremity of the body. Generally speaking, the results of the author’s investigat,ion agreed with that of Chandler’s, except the description of the ventral papillae and the spicules of the male: The author recognized four pairs of small ventral papillae (Fig. 23), which were entirely overlooked by Chandler, who described erroneously that the left spicule was short and the right one long. The fertilized eggs of this nematode were similar to those of G. spinigerum in shape and in size, their shell having a cap on one pole and more marked granulation on t’heir surface. They measured 68-62 X 42-39 P, averaging 66 X 40 CL. 2. Life History Dr. Ash is carrying on the study of this problem in Kew Orleans, the results of which are expect,ed to be published in the near future. In the summer of 1958 the author had a chance to investigate some encysted larval gnathcstomes with him, which were found by him in the muscles of snakes. The results of t,heir investigation were read by Miyazaki and Ash (1959) at the

HUMBN

359

GNATHOSTOMIASIS

G. spinigerum in shape. The hooks were counted on eight head-bulbs, the number of which increased posteriorly like G. spiniSerum, but were far less than the latter: They amounted t’o 29-X (averaging 32.6) on the first row, X5-40 (36.9) on the second, :3845 (416) on the third and 4237 (45.1) on the fourth. (In the case of G. spinigerum, they averaged 44.3, 17.3, 49.6, 52.0, respectively.) GsATHOSTOMA

TCRGIDUM

Stossich,

1902

This nematode was obtained for the first time from an opossum, Didelphis azarae, in Argentina. Over 20 years later, Travassos (19’25) found what he considered to be the same species in the stomach of anot’her kind of opossum, Didelphis aurita in Brazil, and redescribed it in detail. Of his descriptions t,he following items seem to be significant: The cuticular spines had many teeth on t,heir distal edge, covering anterior half of t’he body; the male was provided with nine pairs

FIG. 22. of a female

Extent and G. procyonis.

shape

of cuticular

spines

28th Annual Meeting of the Japanese Society of Parasitology: Sixty-four and thirtyone larvae were obtained from seven of nine water moccasins and from five of ten nonpoisonous snakes, respectively. Their body was pale in color, like larval G. doloresi, and covered with spines as far as the posterior extremity. However, the spines on the posterior half of the body were so small that they needed high magnification to be recognized distinctly. The head-bulb was provided with four rows of hooks, similar to

FIG. 23. Ventral male G. procyonis. I-4: A-I): K: S:

view

of the terminal

Large pedunculate papillae Small ventral papillae Cloaca1 aperture Right spicule

end of a

360

MIYAZAKI

of caudal papillae; the egg looked like that of Trichuris, having two caps on both poles. In North America, Dikmans (1931) investigated two male gnathostomes from the stomach of the opossum, Didelphis virginiuna, in Louisiana, and he called them G. turgidurn provisionally, though he noticed the difference in the number of caudal papillae. His specimens had five, possibly six, pairs of caudal papillae, of which four pairs were large and pedunculated. Meanwhile, Chandler (1932) obtained some sexually immature gnathostomes from the liver of the same opossum, D. virginiana, in Houston, Texas and he named them Gnathostomadidelphis n. sp., pointing out the difference from G. turgidum in the number of male caudal papillae. Besides he considered Dikmans’ specimenswere identical with his G. didelphis. According to his description the male of this nematode has four pairs of large caudal papillae and a pair of small ventral ones. Fortunately, the author could borrow a male specimen from Prof. Chandler, on which his original description had been based, and recognized three, possibly four, pairs of small ventral papillae, instead of one by Chandler (1932). On the other hand, Travassos (1925) illustrated five pairs of large pedunculate caudal papillae in his Fig. 5, which are asymmetric in position and unequal in size. From the author’s experience, all the nematodes belonging to the genus Gnathostoma are provided with four pairs of pedunculate caudal papillae, which are symmetrically situated and each pair of which is almost equal in size and shape. Accordingly the author is inclined to think that Travassos’ specimen had a kind of deformity, which rarely occurs also in another speciesof the present genus, and therefore, to think that G. turgidum and didelphis may be identical with each other. In order to separate these speciesclearly, it is indispensable to compare them again in detail, especially their caudal papillae of the male and their fertilized eggs. GNATHOSTOMA

AMERICANUM

Travassos,

1925 This worm was first found by Travassos (1925) in the stomach of Felis tigrina in Brazil. The author has never investigated

the specimens of this worm; but according to Travassos’ description, cuticular spinesof the body and caudal papillae of the male look like those of G. spinigerum. The fertilized eggs, however, have two caps at both poles, and so are very easily distinguishable from those of spinigerum. HUMAX

GNATHOSTOMIASIS

The first case of the diseasewas reported by Levinsen (1889) in a Thai woman in Bangkok, Thailand. The female worm removed from this patient by Dr. Deuntzer was named Cheiracanthus siamensisn. sp. by Levinsen, which was later identified with Gnathostomaspinigerum. Subsequently, a lot of worms belonging to the genus Gnathostoma was reported from human beings in Thailand, India, Palestine, Malaya, Indonesia, Australia and China by Samy (1918), Morishita and Faust (1925), Heydon (1929), Maplestone (1929)) Prommas and Daengsvang (1934)) Castens (1935)) Maplestone and Bhaduri (1937), Daengsvang (1939, 1949), Maplestone and Sundar (1939), Nishi (1943), Komaya, Kitamura and Komiya (1944), Mukerji and Bhaduri (1945)) Sandosham (1949), Chen (1949), Joe (1949), Witenberg, Jacoby and Steckelmacher (1950), Prijyanonda, Pradatsundarasar and Viranuvatti (1955), and so on. Of the abovementioned countries, Thailand is wellknown as the most highly infested area. Almost all of the worms removed from these cases were considered to be the larvae or sexually immature adults of G. spinigerum, except the two worms described by Maplestone (1929) and Mukerji and Bhaduri (1945), who believed that their specimens were neither G. spinigerum nor hispidum, and the one worm regarded by Chen (1949) as G. hispidum. The author is, however, inclined to think these three specimensbelong to. G. spinigerum. In this country, on the other hand, some specimens of Gnathostoma had been extirpated from Japanese people, of which only one specimen identified by Morishita (1924) with G. hispidum had been indigenous to Japan. Nearly all cases in which no causal worm had been recognized seemto have been confused with Quincke’s edema by practitioners who had paid little attention to the

HUMAN

GNATHOSTOMIASIS

possible occurrence of human ganthostomiasis. About the end of World War II, this disease began to occur in the northern part of Kyushu. The first report on a case of the disease was made by Yoh (1946) from Saga Prefecture and over 100 patients were found by Misao and Hattori (1947) in Fukuoka Prefecture. Afterwards Doi (1950) found 1264 patients among 39,091 inhabitants in the endemic area of the same prefecture. The disease has gradually spread to Shikoku and Honshu and at present it is indigenous, as shown in Fig. 1, to Kumamoto, Nagasaki, Saga and Fukuoka Prefecture in Kyushu; Kagawa and Tokushima Prefecture in Shikoku; and Hyogo, Osaka, Nara, Shiga and Aichi Prefecture in Honshu. Although after the war many people suffered from the disease, no causative agent was ever found from the patients, until Kitamura and Kawai (1949) and Kitamura (1952) recognized the worm histologically in a cutaneous induration of a man for the first time, followed by Miyazaki and Makino (1951), who first extirpated an unbroken worm from a creeping eruption of a Japanese woman. Including t,he above-mentioned Morishit’a’s specimen, t,hese three worms were all larval forms, but Miyazaki and Kikuchi (1954b) obtained an adult male of G. spinigerum from a Japanese woman, confirming that the Japanese strain of G. spinigerum can mat’ure in the human body (Fig. 24). Since then, Okabe and Kuwano (1955), Okabe and Sasaki (1955), Okamura et al. (1955)) Miyazaki and Iino (1956), Morishita, T. (1956), Matsunami et al. (195(i), Hadano et al. (1956), Morishita, K. (1956), Yoshizawa et al. (1957) and Tanase et al. (1957) obtained from patients 10 specimens of morphologically matured G. spinigerum, of which six were males, three were females and the remaining one was unsettled because of its broken body. Thus, over a dozen of the worms were hitherto found from human beings in Japan, which were all regarded as G. spinigerum except one reported by Morishita (1924) to be G. hispidum. The author is inclined to think that Morishita’s specimen was also G. spinigerum.

361

FIG. 24. Lateral vielv of a male G. spinigerunc emerged spontaneously from a woman (head bulb contracted). H : Head bulb L : Lip C : Cervical sac E: Esophagus T: Testis I: Intestine Li: Ejaculatory duct S: Spicules .4: Caudal alae

1. Source of Human Injection Except the result of Golovin’s investigation (1956), it was experimentally clarified that mammalia could not be infected with the nematode by swallowing the infected cyclops, but could be easily infected by ingesting some of the second intermediate hosts harboring third stage larvae of the nematode. Of these hosts the fresh-water fish is significant as the source of human infection. According to Daengsvang (1949)) many living infective gnathostome larvae were found in a kind of fermented food in Thailand, which is mainly made of the raw flesh of fresh-water fish, Ophicephalus stri-

362

FIG.

stomiasis

MIYAZAKI

25.

Important in Japan. Upper Lower:

vectors

: Ophicephalus 0. tadianus

of human

gnatho-

argus

atus, etc. This dish is a favorite of Siamese women which probably explains the higher incidence of gnathostomiasis among females in Thailand. In Japan people like to eat “Sashimi,” the sliced raw flesh of animals, especially of fish. This is the reason why Japanese people so frequently suffer from gnathostomiasis not only in their own country, but also in foreign lands in the tropical and subtropical area. Of the vectors of human gnathostomiasis in Japan, the fresh-water fish Ophicephalus is the most significant, because the fish is widely distributed and its raw flesh tastes very nice to eat. There are two species of the genus in Japan, 0. argus and 0. tadianus (Fig. 25), the former of which came from Korea and has now spread almost throughout the country, but the latter came from Formosa and is now localized in the central part of Honshu. These fish are very highly infected with the encysted third stage larvae of G. spinigerum, almost all of them being parasitic in the flesh of the host. Generally speaking, t’he larger fish harbors the more larvae. In addition to Ophicephalus, the crucian carp (Cyprinus auratus), the goby (Acanthogobius hasta) and the chicken are also the source of human infection, because their sliced raw flesh is commonly eaten by Japanese people. 2. Symptoms The incubation, which means the phase between ingestion of the worm and first appearance of the cutaneous change, varies extremely, but it takes usually from t,hree to

four weeks. In this phase many patients suffer from epigastric pain, nausea or vomiting, which are presumably due to penetration of the gastric wall by the ingested larvae, as well as to disturbance of the liver function by the migrating larvae, which damage the liver t’issue and secrete a kind of toxin (Sagara, 1953; Morita, 1955; Hirakawa, 1959). According to Shimizu (1957) and Kitsuki (1958), the experiment)al rabbits infected with the third st,age larvae showed a change of their serum protein in two bo t’hree weeks after infect’ion, i.e., albumin decreased and globulin, particularly p- and r-globulin increased; Takata’s reaction in serum of the rabbits became positive in 1 t,o 8 weeks after experimental infection. Suga et al. (1954) reported that seven patients examined were all positive in Takata’s serum reaction. Kitsuki (1958) added that the excretory disturbance of the experimental rabbits was seen in bromsulphalein test in 2 t,o 3 weeks after infection. These facts seem to explain the disturbance of liver function in the early stage of gnathostomiasis. The so-called toxin of Gnathostoma, including both secretions and excretions, is presumed to have many factors: Shimizu (1957) found some hemolytic substance, Takizawa (1957) proved the presence of a substance resembling acetylcholine, and Matsuda (1959) revealed the spreading factor containing hyaluronidase and a proteolytic enzyme. These findings are also significant to explain the complicated symptoms of human gnathostomiasis. The larvae migrating in the liver of the host for a while leave it sooner or later and most of them come to the subcutis probably passing through the diaphragm tissue. Then, the cutaneous change, the most conspicuous clinical symptom of the disease, begins to intermittent appear, of which migrating edema is the usual and creeping eruption is the rare form of the disease (Fig. 26). The migration of cutaneous lesion is due to the movement of living gnathostomes. Xagao (1955) described that the worm proceeded at the rate of some 1 cm per hour in the skin of the patient suffering from creeping disease. In order to migrate through the tissue of the hosts, this nematode seems to use not only the movement of its body, but

HUMrtN

GN.4THOSTOMIrlSIY

363

FIG. 26. FOIU cases of gnat,hostomiasis 1,2,3: Migrating intermitt,ent edemlt 4: Creeping eruption also the spreading factor secret,ed from itself, and the above-mentioned “ballonetcervicalsac system” is helpful to swell its head-bulb. The duration and the interval of the edema are extremely variable, but, as a general rule, the swelling continues 1 or 2 weeks at the same portion of the body and becomes shorter in duration afterwards, and its interval, on the cornrary, becomes longer gradually. Generally speaking, the edema is somewhat erythematous, feverish and pruriginous. The pain is usually very slight or entirely lacking, but sometimes it is so severe that gnathostomiasis is easily confused with abscess, appendicibis, cholecystit’is and so on. Histologically it was proved that, the edema is mainly due to the inflammatory

reaction of the tissue and partly to the allergic reaction of it. According to Yamanaka (1958), the extract of the third stage larvae and the adults of G. spinigerum as well as the foster fluid prepared from the larvae produced both Shwart’zman’s and Arthus’ phenomena in guinea pigs, showing that this worm has strong antigenicity and allergenic&y. Besides, he reported t.hat the serum from patients of gnat’hostomiasis was all positive in Prausnitz-Kiistner’s reaction, proving that the passive transfer of gnathostome allergy to non-infected humans is possible. In addit’ion to the above-stated cutaneous changes, some interesting features of the disease were occasionally reported: RIukerji and Bhaduri (1945) in India, Chen (1949)

364

MIYAZAKI

in China, Daengsvang (1949) in Thailand and Witenberg et al. (1950) in Palestine reported six cases of ocular gnathostomiasis in all, from which the causative worms were extirpated. Prommas and Daengsvang (1934), Daengsvang (1949), Okamura et al. (1955) in Japan and Prijiyanonda et al. (1955) in Thailand described six cases of pulmonary gnathostomiasis in all, each of whom coughed up one gnathostome. Recently, Bovornkitti and Tandhanand (1959) in Thailand reported a case of spontaneous pneumothorax complicating recurrent migratory cutaneous swellings, but they could not find the causative agent. By the way, they briefly quoted Tansurat’s review (1955)) in which he reported six cases of pulmonary gnathostomiasis, all of them having coughed up the causative worms. Daengsvang (1939, 1949) reported five cases of intra-abdominal gnathostomiasis, each patient having revealed one hard tumor after laparotomy. Three of the tumors were situated in the ileocecal part of the intestine and the other two were in the gastrocolic region. All tumors harbored one worm each and the worms found were three fully developed males and two immature females. Bodhidat and Punyagupta (1956) reported in Thailand a case of intracranial gnathostomiasis with a definite history of migratory swelling on and off all over the face. The patient suffered from headache, vomiting, drowsiness and stiffneck. Cerebrospinal fluid was high with increased leucocytes, especially eosinophils, and electroencephalography was also abnormal at the same time. The authors thought that the gnathostome left the intracranium through the occipital foramen. 3. Diagnosis The most convenient and reliable means of clinical diagnosis for gnathostomiasis is the skin test. In Japan, 0.05 cc of a 50,000fold saline solution of the antigen prepared from the imagines or larvae of G. spinigerum or doloresi is injected intracutaneously, and 15 minutes later the results are determined from the diameter of the papule and the surrounding red areola. In the case of gnathostomiasis the papule measures more than 10 mm in diameter and is surrounded by red

areola. This method is based on Egashira’s experiment (1951, 1953); on the other hand, Yamaguchi (1951) reported that he injected 0.1 cc of antigen suspended in Coca’s solution. The skin-test is also useful to differentiate the disease from cutaneous paragonimiasis, which occurs not infrequently in Japan and shows the same symptoms. Ando (1957) reported that this cutaneous reaction was elicited intensely by the protein fraction than by the fat or sugar one, which were separated from the extract of larval or adult G. spinigerum; the extract of esophagus of the worm was more antigenic than that of the other part of the worm body and the reaction was positive also by the saline solution, in which either larvae or adults of the worm had been kept, indicating that an antigenie substance came out of the worm body. According to Yamaguchi (1952), Kita (1957), and Furuno (1959), the precipitin reaction in serum from patients is also a valuable means of #iagnosis for gnathostomiasis. In addition to immunological reactions, the blood picture of the patients is also helpful for clinical diagnosis: In the case of gnathostomiasis leucocytes especially eosinophils increase in number, particularly when the edema appears, over 10,000 leucocyt,es and over 50 % eosinophilia being not rare. As a general rule, these changes in the blood picture are marked in the early stage of the disease, and gradually decrease afterwards (Miyazaki, H., 1951). I\;agao (1956a) enclosed five heat-killed third stage larvae of G. spinigerum in two divided portions of his own body, one into the muscular and the other into the skin tissue, and obtained the result that the percentage of eosinophils in the circulating blood began to rise by degrees 24 hours after enclosure, reached the maximum (10.5 %) 9 days after it, and decreasing daily later, returned to normal in 21 days.

4. Treatment and Prevention Egashira (1953) examined in vitro the therapeutic effect of some remedies and showed that I-Diethylcarbamyl-4-Methylpiperazine-Citrate (Supatonin) had the strongest helminthicidal action on larval G. spinigerum among the drugs employed,

HUMAN

GSATHOSTOMIASIS

but it was proved that this remedy had no recognizable therapeutic effect in experimental rats infected with the same worm. Uozumi (1959) examined the resistance to X-rays of the third stage larvae of G. spinigerum, and concluded that X-ray irradiation could hardly be expected to serve as a cure for human gnathostomiasis, because the larval form of the causal organism was deprived of its viability and infectivity only when the X-rays were applied to it in large doses.Anyway, there is not yet any effective medicine available; surgical removal of the worms from cutaneous lesions is the only and the best method of treatment at present. In lucky but rare cases, the causal worms spontaneously creep out of human bodies; otherwise they can survive commonly for several years, sometimes for as long as over 10 years. Consequently, prevention is most important for human gnathostomiasis. Egashira (1953) clarified that the excyst’ed larval gnathostomes were killed within 5 minutes in water at over 7O”C, within 6 hours in vinegar and wit,hin 12 hours in soy. According to Daengsvang (1949) a living infective larva, which was parasitic 1 cm deep in the flesh of fish, could be killed by being treated for at least 5 minutes in boiling water and also be killed after being left in vinegar containing 4 % acetic acid for 545 hours. In conclusion, the way to prevent human infection with Gnathostoma is to avoid all dishes t’hat contain raw or poorly cooked flesh of animals, particularly that of fresh-water fish or chicken. REFEREXCESt

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1836 among the Yangtze Valley particularly in t,he Shanghai area. (Japan.) Repts. Shanghai Sci. Znst. 15, l-4. KOMAYA, G., KITAMLJRA, K., .~ND Kowu.4, Y. 1954b. The second intermediate hosts of Gnathostoma spinigernm Owen, 1836 among the Yangtze Valley and their natural infection. (Japan.) Repts. Shanghai Sci. Inst. 13, 5-22. KOS.~KA, G., AND ITO, T. 1955. Human gnathostomiasis occurring in Hyogo Prefecture, Honshu. (Japan.) Japan. Med. J. 1611, 12601267. LEIUY, J. 1858. Cheirucanthus sociu/is Leidy. Proc. dcud. Natl. Sci. Philadelphia, 11, 25. LEIPER, It. T. 1909. The structure and relationships of Gnuthostomu sianlease (Levinsen). Parasitology 2, 77-80. LEVINSEN, 6. M. R. 1889. Om en ny Rundorm hos Mennesket, Cheiracanihns siamensis II. sp. Videnskubel. Meddel. fra den v&whist. Foren. i lijobenhazlen 323-326. (Quoted from Centr. Bakteriol. Parusitenk. 8, 182, 1890.) MABUCHI, S. 1957. Studies on the development of the larva of Gnathosfoma nipponicum in Eucyclops serrulatus. (Japan. with Eng. abstr.) ;lctu Schol. Med. Gifu 4, 587-636. MAPLESTONE, 1’. A. 1929. A case of human infection with a gnathostome in India. Indian Med. Gaz. 64, 61(t614. MAPLESTONE, P. A. 1930. Nematode parasites of pigs in Bengal. Records Indian Mnsenm 32(Part 2), 77-105. MAPLESTONE, P. A., AND BH~DURI, X. 1’. 1937. Gnathostomiasis in human beings. Indian Med. Guz. 72, 713-715. MAPLESTONE, P. A., AND SUNDER, R. S. 1939. A case of gnathostomiasis with some interesting features. Indian Med. Guz. 74, 479180. *MATSUDA, Ii. 1959. Enzymat,ic studies on the toxin of Gnuthostoma spinigernm. (Japan. with Eng. abstr.) Frrktroka ilctu Med. 50, 2301-2321. MATWNAMI, E., KOBAYASHI, RI., AND MABUCHI, S. 1956. .4 case of gnathostomiasis. (Japan. with Eng. abstr.) Arch. Japan. Chirurg. 25, 760-765. MISAO, T., ANI) HATTORI, K. 1947. On the gnat,hostomiasis cmanea recently occurred in Hyokai Mura, Yamato C;un, Fukuoka Prefecture. (Japan.) Nihon Zgakn 3116, 151-157. MITTER, S. N. 1912. Note on Gnathostomum spinigerum. Parasitology 5, 150. MIYAZAKI, H. 1951. Studies on gnathostomiasis, with particular reference to the progress of the disease in relatively long course of time. (Japanese, with Eng. abstr.) Japan. J. Dermutol. Venereol. 61, 1616.

xii

I. 1950. The first finding of Gnathostoma doloresi in Japan. (Japan.) Japan. J. Clin. Exptl. Med. 2i, 617-619. MIYAZAKI, I. 1952a. Mesocyclops leuckarti and Encyclops serrnlutns as the first intermediate host, of Gnathostoma in Japan. (Japan.) Medicine and Biol. (Japan) 24, 35-37. MIY.IZAKI, I. 1952b. Studies 011 the life history of Gnuthostoma spinigernm Owen, 1836 in J&pa11 (Nematoda: Gnathostomidae). (Japan. with Eng. abstr.) .-lcta Med. 22, 1135-1144. MIYAZ~KI, I. 1952c. on the second st,age larvae of three species of Gnathostoma occurring in Japan (Nematoda: C;natjhostomidae). (Japan. with Eng. abstr.) ;Lctu Itfed. 22, 1+4331441. M1uaz.4~1, I. 1954a. Studies on Gnuthostoma occurring in Japan (Nematoda: (>nathostomidae). I. Human gnathostomiasis and imagines of Gnathostomu. Kycrshu Mem. Med. Sci. 5, 13-27. MIYAZAKI, I. 1954b. Studies on Gnuthostoma occurring in Japan (Nemat,oda: C;nathostomidae). II. Life history of Gnuthostomu and morphological comparison of its larval forms. Kynshn Mem. Med. Sci. 5, 123-139. MIYAZAKI, I. 1955. Morphological studies on some species of Gnuthostoma occurring in foreign lands. (Japan. with Eng. ah&r.) Fnkuoka Actu dled. 46, 1237-1243. MIYAZSKI, I. 1956, 1957, 1958. St,udies on Gnuthostomu and gnathostomiasis. (Japan.) dnn. Rept. Co-oper. Res. (Med.) Minist. Educ. 567574, 429436, 155-162. MIYAZAKI, I., AND ASH, L. R. 1959. On t,he gnathostome larvae found from snakes in New Orleans, U. S. 9. (Japan.) Japan. J. Purusitol. 8, 351-352. MIYAZAKI, I., AND 11~0, H. 1956. A female Gnathostovna spinigerum spontaneously crept out from the soft palate of a woman. (Japan.) Proc. 9th Sonth Bran. Meet. Jap. Sot. Parasitol. p. 38. MIYAZAKI, I., AND ISHII, Y. 1952a. On a gnathostome larva encysted in t,he muscle of salamander, Hynobins. (Japan. with Eng. abstr.) Acta Med. 22, 46774i3. MIYAZAKI, I., AND ISHII, Y. 1952b. An experimental infect,ion of a wild boar with a larval gnathostome encyated in the muscle of salamander, Hynobias. (Japan.) Medicine and BioZ. (Japan) 24, 235237. MIYAZAKI, I., AND TSOBE, H. 1951a. Natural infection of cats in Kyushu with Gnuthostovnu and Clonorchis sinensis. (Japan.) Medicine and Riot. (Japan) 18, 252-254. MIYAZAKI, I., AND ISOBE, H. 19511). (hi natural MIYAZAKI,

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