GENUS STRONGYLOIDES
GENUS STRONGYLOIDES
GENUS STRONGYLOIDES
You also want an ePaper? Increase the reach of your titles
YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.
<strong>GENUS</strong> <strong>STRONGYLOIDES</strong><br />
by<br />
HIROSHI TANAKA
Hiroshi TANAKA, Dr. Med. Sci.<br />
Assistant Professor, Department of lVledical Zoology, Tokyo<br />
Medical and Dental University<br />
I<br />
I<br />
\<br />
I
592<br />
standing pathogenicity of this worm. Often with case reports, experimental<br />
treatment has been included, for example, in those of YOSHINO (1939) and TANAKA,<br />
SHIROMA et al. (1957-60) in human cases, SATO, S. (1933) in dogs with S. stercoralis,<br />
FUJITA et al. (1953), WATANABE (1956), OSHIO(1958) in pigs, and TANAKA<br />
& AMANO (1959, 60) in albino rats with S. ratti. On the various species of<br />
Strongyloides parasitic to animals, several studies on comparative morphology<br />
and ecology were reported by FUJITA (1938) in S. papillosus, TANABE (1938, 39),<br />
TANAKA & AMANO et al. (1959, 60) in S. ratti, TOMITA (1937-41), OSHIO et al.<br />
(1954-58) in S. ransomi and TOMITA (1939-41) in S. fulleborni.<br />
The improved technique for detecting Strongyloides made by SASA et al.<br />
(1957, 58) and TANAKA et al. (1957, 58) came to be applied to the group examina<br />
tion of human stool and enabled epidemiological studies. By recent examination,<br />
the island south of Kyushyu were found to be widely spread with foci of human<br />
strongyloidiasis, and the studies on human strongyloidiasis in this country are<br />
developing from the case reports to the resolution of a problem in the public<br />
health.<br />
II. SPECIES OF <strong>GENUS</strong> STRONG YLOIDES<br />
A. List of Species<br />
After the discovery of Strongyloides stercoralis (BA V A Y, 1876), numbers of<br />
species belonging to Genus Strongyloides were reported from the warm blooded<br />
vertebrates. The identification of the species was usually made by examining<br />
the morphological difference and host specificity, but little difference has come<br />
to be revealed between different species in morphology in consideration of<br />
morphological variations. CHANDLER (1925) integrated species hitherto published<br />
into three species, S. stercoralis, S. papillosus and S. westen', mainly for the<br />
observation of the morphological differences and considered the other species<br />
were race or subspecies of those three ones. On the other hand, SANDGROUND<br />
(1925) expressed his opinion on the identification of species by morpholegical<br />
difference and peculiar behavior of host specificity. This method of identification<br />
is still widely accepted. The species thus accepted are listed in Table 1, though<br />
some may be eliminated as synonym and further definite classification may be<br />
difficult. Among species used in some older times and eliminated in this list,
Table 1. List of species of Genus StTongyloides<br />
Strongyloides stel'coralis ( BA VA Y, 1876) STILES et HASSALL, 1902<br />
S. flilleborni von LINSTOW, 1905<br />
S. cebus DARLING, 1911<br />
S. simiae HUNG et HOPPELI, 1923<br />
S . canis BRUMPT, 1922<br />
S. stercol'alis felis CHANDLER, 1925<br />
S. cati ROGERS, 1939<br />
S. tumefaciens Price et Dimand, 1941<br />
S. vituli BRUMPT, 1921<br />
S. ovocinctus RANSOM , 1911<br />
S. papillosus (WEDL, 1856) RANSOM, 1911<br />
S. westeri IHLE, 1917<br />
S. nasua DARLING, 1911<br />
S, mnsomi S CH WARZ et ALICATA, 1930<br />
S. ratti SANDGROUND, 1925<br />
S. allbal'i MIRAZA et NARYAN, 1935<br />
S. mlti ondatl'ae CHANDLER, 1941<br />
S. sigmodontis MELVIN et CHANDLER, 1950<br />
S . agouti GRIFFITH, 1940<br />
S. robustus CHANDLER, 1942<br />
S. chapini SANDGROUND, 1925<br />
S. avium CRAM, 1929<br />
S. oswaldi TRA VASSOS, 1930<br />
S. ophidae PEREIRA , 1929<br />
S. longus (GRASSI, 1884) is a synonym of S. papillosus, S, suis (L UTZ , 1885) von<br />
LINSTOW, 1905 was erroneous expression, because no paper was published by<br />
L UTZ himself and S. vivzparus (PROBSTMA YER , 1865) and also S. bovis (VRYBURG,<br />
1907) were pointed out by RANSOM (1911) as false identification and transferred<br />
to the other genus.<br />
The species of Strongyloides found and reported in this country were six;<br />
S. stercoralis, S. jiilleborni, S. papillosus, S. ransomi, S. ratti and S. westeyz·.<br />
B. Identification by Morphological Difference<br />
Morphological difference has been often studied between the species considered<br />
widely distinguishable, but the information was hardly obtained as to<br />
their difference. CHANDLER (1925) reported the difference in the shape of tail<br />
of females in parasitic stage between S. stercoralis group and S. papillosus group,<br />
but SANDGROUND (1925) disagreed. The shapes in various stages, first published<br />
as peculiar to certain species, were later mostly ignored. The shapes peculiar<br />
to a species were often reported in the observation of body length, position of<br />
organs, ratio of length from head to each organ by the body length, cuticular<br />
593
594<br />
striation, shape of tail, number of head mamillae, shape of uterus and ovary<br />
in parasitic female and type of branch in tail ending of filariform larva, but<br />
later difference was scarcely found from the observation of variations. There<br />
may exist a room to make comparative studies on morphology among species,<br />
because there are some morphologically characteristic species like S. westeri of<br />
which body length is largest and like S. stercoralis which is evacuated in human<br />
stool in rhabditoid larvae. Much attention should be paid for comparison on<br />
the body length, position of organs and shape of ovary of the parasitic females.<br />
C. Relationship to the Host<br />
The species of this genus have many problems about identification and<br />
specific independency because of less morphological difference between species.<br />
However, considering with the relationship to the host specificity, choice of a<br />
species can be limited to a restricted range. Naturally a species of Strongyloides<br />
does not always infect on one species of host animal but it selects only a few<br />
animals as hosts. For instance, S. stercoralis of man can infect on monkeys,<br />
dogs and cats, and S. ratti of Rattus norvegicus has a conspicious ecology hardly<br />
to infect on mice. By those reasons, identification is not always difficult when<br />
the choice of hosts is considered with the morphological observations. The<br />
species lately accepted are the result selected by the above mentioned reasons<br />
and convenient to classify the species of Strongyloides. In this situation there<br />
may be still somewhat confusion among species related to S. stercoralis, those<br />
to S. fiilleborni, those to S. papillosus and those to S. ratti, and integration will<br />
be made in those groups in future.<br />
III. HOST SPECIFICITY<br />
From the experimental infection made by AUGUSTINE (1940), the host speci<br />
ficity of a species of this genus is important for identification. In this respect,<br />
experimental infection has been carried out on the various species on animals.<br />
S. stercoral is was first transferred from man to animals by FOLLEBORN (1911)<br />
and successfull infection took place on a dog. TASHIRO (1912) also made a<br />
successful experiment of percutaneous infection of S. stercoralis on three dogs<br />
out of five and the incubation period was 16 days. OHIRA (1918) transferred<br />
from man to mice, laboratory rats, guinea pigs, rabbits, dogs, cats and monkeys
596<br />
concerning with recent classification. In the experiments made by OSHIO &<br />
FURUT A (1954) and OSHIO (1956), infective larvae of S. ransomi from pigs could<br />
invade hide of rabbit, guinea pig, mouse, laboratory rat, hen and frog but real<br />
infection took place only in rabbits. In observation of 20 rabbits with succes<br />
sful infection, the course of infection differed a little from that in pigs as in<br />
prolonged incubation period, 10 to 13 days, less number of eggs in fecal pillets<br />
and delayed development of eggs in culture. From this viewpoint, rabbits were<br />
thought to be inadequate host for this species.<br />
As a peculiar nature of S. ratti, SANDGROUND (1925) expressed it did not<br />
infect on rabbits, guinea pigs and mice. ROMAN (1956) made experimental<br />
infection to mice in detail. From his result, young mice were susceptible for<br />
the infection of S. ratti, mature mice were resistant and also the mice injected<br />
with a large dosis of cortisone were susceptible. TANAKA et al. (1959) experienced<br />
transient infection in five mice out of six. As the natural hosts besides Rattus<br />
norvegicus, VANNI (1937) recorded Mus musculus, ROMAN (1951) added Microtus<br />
arvalis, Apodemus sylvaticus, Clethrionomys glareolus and AMANO (1959) found<br />
Rattus rattus.<br />
S. sigmodont£s discovered by MELVIN & CHANDLER (1950) from cotton rat<br />
could not infect on hamsters, guinea pigs, mice, rabbits nor on rats. That<br />
peculiar choice of host was thought to be the differential point of this species<br />
from S. ratti.<br />
From the experimental infection as mentioned above, the host specificity<br />
of each species of Genus Strongyloides is thought to be definitely restricted.<br />
The host specificity becomes more confirmed when the erronous identifiction<br />
hitherto published is adjusted following the recent knowledge of classification.<br />
Each species of Genus Strongyloides hitherto found selects only one or a few<br />
kinds of closely relating animals as the adequate host even though a kind of<br />
animal is susceptible to the infection of different species of Strongyloides or a<br />
certain host, first thought to be resistant to a species, was later found to be<br />
susceptible to the same one.<br />
IV. MORPHOLOGY<br />
Strongyloides develops both in parasitic and free living generations and
598<br />
Fig. 2. A-F : S. stel'c01'alis A, B : rhabditoid larva, C: filariform larva,<br />
D : male in free living stage, E : anal part of male, F: female<br />
in free living stage, G: S. fiilleb01'ni, female in parasitic stage<br />
presents complicated life cycle. The shape varies distinctly in stages, parasitic<br />
female, rhabditoid larvae, filariform larvae, male and female in free living stage.<br />
Figure 1 presents the whole course of life cycle, root of infection and relation<br />
ship of all stages. Shapes of all stages are illustrated in Fig. 2.<br />
Morphological observations of each stage were often reported, but consi<br />
deration was little paid in the individual variations. The method of measuring<br />
criteria is not still confirmed. FAUST (1933) used three criteria; a (body length/<br />
body width), f3 (body length/length of esophagus) and r (body length/tail length)<br />
and others presented the position of organs using two values, distance from<br />
head to each organ and its ratio to the body length as FENG (1933) applied to<br />
the differentiation of microfilariae and COBB (1945) to the classification of the<br />
free living nematodes. COBB'S method of measurment is thought to be conve<br />
nient for the morphological studies on Strongyloides because there needed a<br />
delicate differentiation for comparison between the hard distinguishable species,<br />
for morphological alteration in following the course of development and for<br />
comparison between the larvae of many other species. Morphological studies<br />
with measurement in detail were reported by those workers, FUJITA (1939) about<br />
all stages of S. papillosus, TOMITA (1939) about all stages of S. fiilleborni and of<br />
S. ransomi, DESPORTES (1944, 45) about all stages of S. stercoralis, SANDOSHAM (1952)<br />
and TANAKA (1957 c) about free living stage of S. stercoralis, SANDGROUND (1925)
about parasitic female of S. ratti and TANAKA et al. (1959) about filariform<br />
larvae of S. ratti. When those measuring values are compared among different<br />
species, difference is scarcely seen in free living stages, but only slight diffe<br />
rence may exist in body length of the parasitic females among species as<br />
reported 1.85-3.03 mm in S. ratti (SANDGROUND, 1925), 1.75-2.35 mm in S. stercoralis<br />
(DESPORTES, 1944, 45), 2.65-3.84 mm in S. fiilleborni (TOMITA, 1939), 3.36-4.26 mm<br />
in S. ransomi and 4.98- 5.56 mm in S. papillosus (FUJITA, 1938).<br />
Often difference was observed in size between eggs in parasitic females and<br />
those after oviposition. SHIMURA (1919 a) described that the eggs in the uterus<br />
of S. stercoralis did not develop there, measured 56-64,u x 22-30,u in dogs and<br />
60-77,u x 28-32,u in men and the eggs after oviposition were 60 x 40,u in dogs and<br />
70 -43,u in men. ITO (1932) reported the size of eggs in the uterus of S. stercoralis<br />
were 66 -83,u x 36-45 ,u and those after oviposition were much larger, measuring<br />
75 -88,u x 40-60,u. MATONO (1931) expressed the size of eggs were 44.8-70.0,u x 16.8-<br />
26.6,u . TANAKA et al. (1959) measured eggs of S. ratti in feces immediately after<br />
evacuated and the size was smaller than that of S. stercoralis and was 53.0,u in<br />
an average of long axis with unbiased variance u 2 =15.12 and 27.4,u in an average<br />
at short axis with u 2 =2.45.<br />
KREIS (1932) and FAUST (1933) reported the discovery of the males of S.<br />
stercoralis in parasitic stage, but there has not yet been such report in this<br />
country.<br />
Eggs from parasitic females grow up to rhabditoid larvae (rh 1) and then<br />
to filariform ones (f 1) in direct development and eggs from adults in free living<br />
stage also develop to rhabditoid larvae (rh 2) and filariform ones (f 2) in indirect<br />
development. Comparison was often made between those larvae in direct and<br />
indirect developments. FUJITA (1938) reported the size of genital primordium<br />
of rh 1 in S. papillosus was 10-17,u and somewhat larger than that of rh 2<br />
measuring 10-12,u . LEE (1930) observed the same results in S. stercoralis and<br />
LUCKER (1934) noticed no difference in S. ransomi. From the observation tried<br />
by NISHIGORI (1938) in S. stercoralis, the difference was clarified as following;<br />
in f 1, bodies were 450-549,u (486,u in an average), in length genital primordium<br />
measured 21-27,u (25,u in an average), and consisted of 12-22 cells (18.9 cells in an<br />
average), while in f 2 they were 560-635,u (612/l) in length, and genital primordium<br />
was 8.4-12,u (9.1,u) in size, and consisted of 3 to 4 cells. TOM IT A (1939) found<br />
the difference in S. fiilleborni and in S. ransomi, but no remarkable difference<br />
was proved by LEE (1930) in S. stercoralis, nor by FUJITA (1938) in S. papillosus.<br />
The split of the tail ending is characteristic in the filariform larvae of<br />
Strongyloides. FUJIT A (1939), having observed the larva of S. papillosus ventrodorsally,<br />
found that the tail was divided into three points. The same results<br />
599
600<br />
were revealed by AucATA (1935) in S. papillosus and by SANDOSHAM (1952) in S.<br />
stercoral is.<br />
In discussion about the existence of spear like structure around mouth<br />
cavity of the adults in free living generation, FUJITA (1938) proved the existence<br />
of such structure, three in number, in S. papillosus. The eggs in the uterus of<br />
females in free living stage were 51.1 x 39.4fL in size in an average of 58 eggs<br />
in S. stercoralis (TANAKA, 1957).<br />
Histochemical observation has recently been studied. YAMAGUCHI (1958)<br />
examined distribution of DNA, RNA, polysaccaride and phosphatase on rhabdi<br />
toid larvae, fillariform larvae and on migrating larvae in lungs in S. ratti, and<br />
also the alteration of those distribution along the development. TSUKASA<br />
(1959) made a similar observation on the free living stages of S. stercoralis.<br />
By the observation of KOBAYASHI & T AKIKAW A (1959) on the excretory<br />
system of S. ratti in all stages, completely developed excretory system in para<br />
sitic females composed H shape as a whole, cervical gland opened at excretory<br />
bridge, connecting to the oesophageal gland and oesophagus, and those structures<br />
were cosely related to those of genus Rhabditis.<br />
INATOMI et al. (1963) observed structures of the filariform larvae of S. stercoralis<br />
using electronmicroscope, clarified peculiar flatten lateral alae, absence<br />
of sheath and structure of fine cuticular striations.<br />
v. THE ROUTE OF INFECTION<br />
A. Peroral Infection<br />
Peroral infection was first proved by LEICHTENSTERN (1898) with S. stercoralis.<br />
Later, FOLLEBORN (1911) clarified the invading site of larvae was the level higher<br />
than stomach at the peroral infection in dogs. TANABE (1938 c) tried successful<br />
peroral infection in 7 rats with S. ratti. KAWAMOTO (1961) examined and knew<br />
that the filariform larvae could be alive only a short period of time in gastric<br />
fluid, 50 per cent of larvae being dead in 2 or 3 hours and all within 5.5 to 6.5<br />
hours. In comparison of the rates of establishment of parasitism among<br />
the different origin of infection, using S. ratti and albino rat, 44.9 per<br />
cent reached to the intestinal mucosa by cutaneous application, 33.8 per cent<br />
by subcutaneous injection, 7.7 per cent by dropping on the mouth cavity and
2.5 per cent by forced introduction into stomach, and concluded the main route<br />
of natural infection was percutaneous.<br />
B. Percutaneous Infection<br />
There have been tried several experiments of percutaneous infection of<br />
Strongyloides by van DURM (1902), Looss (1905) and RANSOM (1907). TASHIRO<br />
(1912) successfully infected S. stercoralis to dogs percutaneously. KOSUGE (1924)<br />
studying the invading mechanism of filariform larvae, proved that those larvae<br />
could penetrate paper, cool hide of warm blooded animals and frog's skin, and<br />
no warmth was needed at the site of infection and nor choice of host was seen<br />
at the invasion. OSHIO & FURUTA (1955 a) found the spreading factor in the<br />
extract of larvae of S. ransomi using intradermal injection of the extract with<br />
indian ink on the hide of mouse and rabbit and also found the faint existence<br />
of hyaluronidase by the methode of reduction of viscosity of hyaluronic acid.<br />
Furthermore, they considered the participation of hyaluronidase at the invasion<br />
of larvae besides larval activities because the larvae could invade in larger<br />
number at the presence of hyarulonidase.<br />
C. Perianal Reinfection<br />
LEICHTENSTERN (1905) assumed certain kind of internal reinfection when he<br />
met a patient who discharged Strongyloides continuously for 14 years. And the<br />
way of reinfection was thought to be from perianal region similar to the hook<br />
worms because the perianal reinfection (Autoreinfektion) had been just clarified<br />
at that time as one of the roots of infection. FOLLEBORN (1926) agreed the<br />
assumption of perianal reinfection of Strongyloides from the two reasons; one,<br />
the existence of perianal erruptions in patients of Strongyloides and the other,<br />
his negative experiment (1914) to the intestinal reinfection proposed by OHIRA<br />
(1913). But little proof is seen from the recent know lege in the experiment<br />
tried by FOLLEBORN (1914) to neglect the intestinal reinfection.<br />
D. Autoinfection (Intestinal Reinfection)<br />
OHIRA (1913) observed the peculiar picture of histology, the filariform larvae<br />
penetrating into mucosa of colon till muscular layer in two autopsy cases of<br />
human strongyloidiasis and constructed a new type of reinfection, in which<br />
rhabditoid larvae developed to filariform larvae in the intestinal canal, and<br />
the latter invaded into the mucosa of colon. Then OHIRA (1918) detected filari<br />
form larvae in the stool of dogs immediately after evacuation, and SHIMURA<br />
(1918 a) also found filariform larvae in 10 per cent of discharged larvae in human<br />
stool at evacuation, and proved larval transformation in the intestines. SHIMURA<br />
(1918 a) observed in a patient continuous avoiding of filariform larvae in his<br />
sputum even after perianal cleaning was lasted. SHIMURA (1919 b) also introduced<br />
the stool, containing merely rhabditoid larvae, into the intestines of the intact<br />
601
602<br />
dogs, made the dog infected and proved the intestinal reinfection. NISHIGORI<br />
(1928) further proved intestinal reinfection from dog infections, in which the<br />
rate of infective larvae in stool increased when the dog was constipated by the<br />
use of large dosis of subnitrate of bismuth and the filariform larvae were detected<br />
in large number from the peritoneal cavity, pleural cavity, liver, lungs and<br />
trachea when the lower portion of colon was made tight or constipated. And<br />
he clarified that the development of rhabditoid larvae into filariform larvae<br />
was readily completed in other organs than intestinal canal, by detecting<br />
filariform larvae in lungs after rhabditoid larvae were introduced into the<br />
femoral vein of dogs or into peritoneal cavity of mice. Autoinfection thus<br />
proved by those serious experiments is an important root of infection to.<br />
consider pathogenicity of this worm and the treatment of strongyloidiasis.<br />
E. Internal Migration<br />
FDLLEBORN (1911-14) studied on the internal migration and proved the larvae<br />
nessesarily once passed through the lung. At the intestinal reinfection,<br />
ASKANAZY (1900), OHIRA (1913) and NISHIGORI (1928) found the larvae invading<br />
into lymphatic vessels and in autopsy of dogs, and NISHIGORI observed thedestruction<br />
of mesenchymal lymphatic nodes at ileocoecal region. Nishigori,<br />
furthermore considering with the fact, observed that the filariform larvae could<br />
be detected from the peritoneal and pleural cavities, a nd arranged the course<br />
of internal migration into following three series;<br />
1) mucosa of colon-lymphatic vessel-vein (or peritoneal cavity)-lung<br />
2) intestinal wall-peritoneal cavity-liver-vein-Iung or peritoneal cavitydiaphragm-pleural<br />
cavity-lung<br />
3) capillary vessel of intestinal wall-lung<br />
From the result of the histological observation of percutaneous infection of<br />
S. ransomi to pigs, OSHIO & FURUTA (1955 b) found the larvae penetrated along<br />
capillary vessels and veins and then entered lymphatic vessel. OSHIO (1956)<br />
detected larvae in the above mentioned experiment at profound cutaneous layer<br />
after 5 minutes, at skin and local lymphatic node after 4 hours and at only<br />
liver and lungs after 24 and 47 hours. Similar process was seen when S. ransomi<br />
was transplanted into rabbits, mouse and guinea pigs and the migrating root<br />
was revealed as lymphatic vessel-vein-Iungs at percutaneous infection.<br />
The course after the lungs was clarified by FOLLEBoRN (1914), YOSHIDA<br />
(1918) and FAUST (1933, 35), the larvae passing through trachea, esophagus and<br />
stomach, finally lodge at Lieberkiin's gland in duodenum establishing full<br />
development. FOLLEBoRN (1914) and FAUST (1933, 35) pointed out the fact that<br />
the larvae in the course of internal migration parasitized and developed com<br />
pletely in the epithelium of the respiratory tract (heterotopic parasitism).
604<br />
from the experiments that eggs from feces of a rat infected with a single larva<br />
of S. ratti grew up both in direct and indirect developments, and such infection<br />
with a single larva continued in 33 generations successively, concluded that the<br />
existence of parasitic male was doubtfull and unnecessary for maintaining<br />
generations and that the parasitic females were homogonic in nature without<br />
diciding whether hermaphroditic or parthenogenetic. YOKOGAW A & MORISHITA,<br />
K. (1953) also described a negative expression to the existence of parasitic<br />
males. From any study, no decision has not been rendered to the character<br />
of the parasitic females as yet.<br />
The eggs in uterus reported by OHIRA (1913) and SHIMURA (1919) were<br />
monocellular, on the other hand, MATONO (1931) observed in eggs of various<br />
stages from single cell to larva and eggs becoming larger near vulva. In the<br />
mucosa of duodenum, eggs encapsulated by the sheath structure were found in<br />
S. stercoralis by SHIMURA (1919 a) and ITO (1932) and in various other species of<br />
Strongyloides. Rhabditoid larvae of S. stercoralis had been known to molt once<br />
before evacuation, and OHIRA (1913) found that the molting took place<br />
immediately after the larvae hatched.<br />
B. Development in Free Living Generation<br />
The eggs or rhabditoid larvae in stool, being molting, develop either to<br />
filariform larvae (direct development) or to adult worms (indirect development).<br />
From the observations of partial development of body in S. stercoralis (TANAKA,<br />
1957, 58; MIY AGAMI, 1960) and in S. ratti (T AGAW A, 1960), the elongation of the<br />
body takes place mostly at the esophageal part of the rhabditoid larvae in the<br />
direct development and, on the other hand, the body grows up in almost the<br />
same rate or rather more at the intestinal parts in the indirect development.<br />
The temperature at which S. stercoralis enables to exist was reported as<br />
15° -40°C. by NISHIGORI (1928). In the observation of the development at 20°C.<br />
in rhabditoid larvae of S. stercoralis, it took two days for the complete develop<br />
ment of filariform larvae, two or three days for males, and more than three<br />
days for females, a little later than males.<br />
In S. ratti which is evacuated at the stage of egg, hatching began 4 hours<br />
after discharge and did not all finished after 24 hours and thus the period of<br />
time till hatching varied in wide range and was 13 hours in an a verage (TAN AKA,<br />
1959). Successive cultivation of free living stage was made by BEACH (1936) in<br />
S. simiae for three generations on the slant similar to the bacteriological<br />
study. The result showed that a female layed 60 to 80 eggs in whole life, the<br />
eggs from the unfertilized female were deformed and no hatching was seen.<br />
The optimum temperature for the development varies by species, as being<br />
around 30°C. in S. stercoralis (TANAKA et al., 1958) and a little lower 24° to 28 °C.
in S. mtti (TANABE, 1938 a).<br />
C. Direct and Indirect Development<br />
The resolution has not yet been attained for the mechanism which decides<br />
the development of larvae either in direct type or in indirect one, though the<br />
problem was tendered at the beginning of the studies of Strongyloides and<br />
various examinations and theories have already been performed.<br />
1. The difference of strain<br />
By the difference of strain, some strain trends to develop directly and the<br />
others indirectly. This theoretic consideration was supported by LEICHTENSTERN<br />
(1889), SANDGROUND (1925, 26), FAusT (1930), GRAHAM (1935-39), CONTACOS (1957)<br />
from different reasons by their experiments.<br />
2. The fertilization<br />
SANDGROUND (1926) concluded that the parasitic females were hermaphloditic<br />
111 nature and KREIs (1932) and FAusT (1933) thought those were females in<br />
bisexual parasitic generation. Those workers without experimental proofs<br />
thought that the direct development took place from the fertilized eggs and<br />
indirect development from the unfertilized ones.<br />
3. The environmental influence<br />
On the other hand, there have been numbers of reports in which the larvae<br />
hatched from the eggs were genetically homologous and the types of develop·<br />
ment were determined by environmental influences.<br />
HASEGAW A (1924) reported that S. stercoralis developed mainly directly at<br />
7-11 °C. a nd mainly indirectly at 30-37°C.. In the observation of NISHIGORI (1928),<br />
S. stercoralis similarly developed mainly indirectly at the temperature between<br />
28°C. and 34°C., and mainly directly at the temperature warmer or cooler than<br />
the above mentioned temperature. The other influences pointed out by<br />
NISHIGORI were that the direct development occurred in the media of little nutri<br />
tion, and the development was almost arrested or, if did not all arrested, only<br />
direct development was seen on the following conditions; replacement of air<br />
in the culturing chamber with hydrogen, carbon dioxide, methan or sulphurous<br />
acid gas or addition of mercuric chloride or cresol. On the other hand, by<br />
addition of oxygen gas to the culturing chamber or basic solution to the<br />
media indirect development occurred in larger chance. Therefore he thought<br />
conclusively that the direct development took place on the suitable environmental<br />
conditions for the worms. TANABE (1938) also examined the influences of the<br />
environmental conditions using S. ratti, and difference was hardly observed in<br />
the ratio of direct and indirect developments at the temperature between 11 °<br />
to 37 °C. neither at pH 6.8 to 8.6. Little influence was also scarcely seen when<br />
he used tap water, spring water, Lock's solution, half Lock's solution, 1.0% KCI<br />
605
606<br />
and 0.5% KCI solution as the liquid of media. But the ratio of indirect develop<br />
ment increased in the presence of much broth (stool 2 g, 10% broth 8 cc and<br />
water 4 cc).<br />
The environmental influences were also accepted by BRUMPT (1921) using<br />
S. papillosus, KAGY (1933) S. stercoralis, SANDGROUND (1926) S. fiilleborni and S.<br />
stercoralis and BEACH (1936) S. simiae respectively but disagreed by GRASSI,<br />
LEICHTENSTERN, Looss, BRAUN (1899), GALLIARD (1951), and final conclusion has<br />
not yet been attained.<br />
D. Ecology of Filariform Larva<br />
Relationship between the temperature and the movement of filariform larvae<br />
of S. stercoralis was observed by SHIRASAKA (1958). This relationship was ex<br />
pressed as a formula log Y =0.322 t+ 1.0761 , when Y was the frequency of the<br />
pendulum motion of the head per minute and t was temperature, the optimum<br />
condition for movement was 20° to 25°C. The highest temperature tolerable<br />
was 45 °C. while at O°C. larvae could be alive for 16 days. In the experiment<br />
made by KAWAMOTO (1961), the larvae of S. stercoralis and S. ratti could keep<br />
alive for 5 days at 38°C. , 2 days at 40°C., 110 minutes at 44°C. and 6 days under<br />
10°C. And at 40°C. S. stercora lis could be kept for longer period of time than S.<br />
ratti, but at cooler condition than lOoC. the result was reversal. In 10% solution<br />
of hydrochloric acid, the larvae of both species died immediately but in 0.25%<br />
solution, S. stercoralis lived for 4 hours and S. ratti for 5 1/2 hours.<br />
SATO, S. (1933 b) affected chemicals to the larvae of S. stercoralis and che<br />
micals which showed larvicidal effect were absolute alcohol, 70% alcohol, 3%<br />
labon, 5% carbol solution, Lugol's solution respectively in stronger order. Dead<br />
• time of 0.1 % mercuric chloride solution was 60 minutes and those of Stibnal<br />
and Fuadin were 3 to 4 days. The larvicidal effect was seen in 9 kinds of dye<br />
chemicals among which mercurochrom and flavicid were strong and rivanol,<br />
trypaflavin, chrystal violet, dahlia, gentian violet, pyronin, methyl violet were<br />
weak. Similar examinations were made by KAWAI (1935) using S. stercoral is<br />
and by TOMITA (1938) with S. ransomi. The results, almost similar in both ex<br />
periments, indicated that the larvae were susceptible to halogens, especially to<br />
iodine, being dead immediately in tincture of 1% iodine or Lugol's solution,<br />
and also to acids, alkalines, disinfectants and anthelmintics (carbon tetrachlo<br />
ride, nematol, thymol) but resistant to the sterilizing dyes.<br />
OSHIO & TAKAHASHI (1958) observed the reduction of hatching rates of eggs<br />
of S. ransomi in participation of various kinds of chemicals. The reduction<br />
was most remarkable in the tincture of iodine and then in 5% HCI , BHC<br />
(hatching rate 0.7%), 5% NaOH, 5% carbol, 5-1% Neo-Gikuron cresol solution.<br />
For general practical application, spraying of 3% dust of BHC in a density
30 g/m 2 was recommended to protect the pigs from the infection of S. ransomi<br />
and the protective effect lasted for 2 weeks.<br />
VII. METHOD OF DETECTION<br />
For the detection of Strongyloides, the stool was generally used while JONES<br />
(1950), JOHNES & ABADIA (1954) showed examination of duodenal fluid was more<br />
sensitive. On the other hand, COUTINHO (1954) reported worse result in the<br />
detection from duodenal fluid. As the indirect method of detection, intradermal<br />
reaction was sometimes examined but the study has not yet completed for<br />
practical use.<br />
A. Distribution of Rhabditoid Larvae in Stool<br />
The distribution of the larvae of S. stercoral is was examined by TANAKA,<br />
TOKURIKI et al. (1958). The number of larvae was counted in 10 mg of stool<br />
samples collected from various parts of a fecal column, parts being distinguished<br />
advancing or rear sides and superficial or inner parts. As the results, the<br />
distribution was Poison's type or normal type at the transversal plane of a<br />
stool column and also recognized as Poison's type in a column as a whole. On<br />
the finer calculation, density of larvae differed between advancing and rear side<br />
and also between inner or superficial parts and more larvae presented at the<br />
advancing side and superficial parts.<br />
B. Techniques for Detection<br />
The detection of S. stercoralis by smear method was made by microscopical<br />
discovery of rhabditoid larvae, and it was hard to find out at low tern·<br />
perature below 20°C. because movement was hardly seen at cool condition.<br />
By addition of water in smear specimens, morphological difference was made<br />
ease even if the density of larvae was reduced. The pathway of larvae was<br />
often observed as light line in the fecal smear so larvae could be detected chasing<br />
along those pathways (TANAKA, 1957).<br />
Floatation techique in the saturated brine solution was applied to the detec·<br />
tion of S. ratti, S. ransomi, S. fiilleborni which were discharged into feces as the<br />
form of eggs (WATANABE, 1956; OSHIO & TAKAHASHI, 1958; AMANO, 1959).<br />
At the condensation technique by means of centrifugalization, care should<br />
be payed to use the adequate mesh of the screen net in the procedure of filtra-<br />
607
608<br />
tion of fecal emulsion because detection was sometimes failed especially in S.<br />
stercoralis when fine mesh was applied (TANAKA, 1957).<br />
Detection by means of extraction of larvae into water has been sometimes<br />
tried. NISHIGORI (1928) put a stool mass in a side of a Petri dish which was<br />
filled with some lukewarm water, transfered the water into centrifuging tube<br />
after a while and then obtained larvae by concentration with centrifugalization.<br />
TANAKA (1957 b) put 3 g of stool on a metal screen which was settled on a Petri<br />
dish filled with warm water at 40°C., kept the whole apparatus in an incubator<br />
at 37 °C. for 30 minutes and then after removing the wire net observed the<br />
bottom of the Petri dish with a stereomicroscope (Fig. 3). And also numbers<br />
of methods similar to the Baermann's apparatus were applied and showed<br />
satisfactory results.<br />
Polyethylen sheet<br />
Rubber band<br />
_++-_Filtration paper<br />
A<br />
Water<br />
B<br />
Warm water<br />
Fig. 3. A: Test tube cultivation method<br />
B : Warm water extraction method<br />
Petri dish<br />
Among numbers of cultivation technics, a method using filtration paper and<br />
test tube, improved by SASA, HAYASHI, TANAKA et al. (1957) from the method<br />
originated by HARADA & MORI (1951) for the purpose of detection of hook worms,<br />
was convenient for mass examinations for its simple procedures and satisfactory<br />
detection. In this procedure, first approximately 0.5 g of stool is smeared on a<br />
half side of a tape of filtration paper, the paper advancing the unpainted side<br />
is introduced into the bottom of a test tube which contains 3 cc of water. The
tubes, after the opening is covered with plyethylen sheet and rubber band are<br />
incubated at 25 °C. for several days then the filariform larvae gathered in the<br />
water and can be detected (Fig. 3).<br />
When the test tubes were incubated at 28 °C. (TANAKA, 1958) the ratio of<br />
daily occurring numbers of larvae to all appeared within 8 days was 78.0%<br />
within 2 days, 90.5% in 4 days and 99.2% in 6 days respectively and the appearance<br />
of Strongyloides was faster than hookworms. In comparison of incubating<br />
conditions among temperature, 20°, 30° and 37 °C. and among period of days,<br />
2, 4, and 8 days (TANAKA, TOKURIKI et al. 1958, TANAKA 1958) the largest number<br />
of larvae appeared at 30 °C. for 8 days then 20°C. 8 days, 30°C. 4 days, 37°C. 4<br />
days in order but the larvae were all dead and degenerated at 37"C. for 8 days.<br />
C. Comparison of Techniques<br />
Comparison was made among different techniques of detection from the<br />
same stool samples (TANAKA, 1958; TANAKA, TOKURIKI et al., 1958), after 3 hold<br />
examinations, average number of detected larvae was 500.0 by Stoll's counting,<br />
2.1 in a specimen of smear technique, 3.3 in a smear slide by the concentration<br />
with centrifugalization, 183.6 using 3 g of stool by water extraction technique and<br />
227.4 by test tube cultivation technic using 0.5 g of stool respectively and the<br />
latter two techniques were known to be satisfactory. In comparison between<br />
smear and test tube cultivation techniques for the practical use at mass<br />
examinations, SASA, TANAKA et al. (1958) found 5 cases (35.8%) by smear technique<br />
and 13 cases (94.0%) by test tube cultivation technique among 14 carriers<br />
of S. stercoralis. In the similar comparison, SASA, TERUYA et al. (1958) detected<br />
6.8% by smear technique and 99.1 % by the test tube cultivation technique among<br />
138 carriers and TANAKA, KUMADA et al. (1959) found 69.4% by the smear and<br />
61.1 % by the cultivation among 36 cases.<br />
TANAKA & AMANO (1959) and AMANO (1959) compared quantitatively among<br />
smear methods, the floatation technique with saturated brine solution and the test<br />
tube cultivation technic using S. ratti. When the volume of feces used was<br />
10 mg in a smear, 100 mg at the floatation and 300 mg by the cultivation, and<br />
large numbers of fecal samples were compared among three techniques,<br />
correlation was known to be exist between egg counts detected by the smear<br />
technic (X), those by the floatation (Y) and by the cultivation (Z) as the following<br />
formulas: Y =40.3 X+653.0 and Z=4.3 X+353.5.<br />
D. Immunological Studies<br />
SATO, S. (1933 a) tried intradermal reaction with 3% aqueous solution of<br />
filariform larvae of S. stercoralis, with successful result of 7 strong positives<br />
among 8 carriers while negatives in 9 control persons. In the dogs and guinea<br />
pigs sensitized with this antigen solution, intradermal reaction appeared strong<br />
609
610<br />
positive but did not always show remarkable specificity. TOMITA (1941 e)<br />
observing short longevity of the filariform larvae of S. ransomi and S. fulleborni<br />
in human serum and also that of S. fiilleborni in the rabbit serum thought that<br />
the congenital immunity should exist in the serum of the inspecific hosts.<br />
SHELDON (1937) experimentally proved the development of aquired immunity of<br />
the rats against S. ratti.<br />
VIII. EPIDEMIOLOGY<br />
A. Distribution of S. stercoralis in Japan<br />
After HATORI (1898) reported a case of strongyloidiasis in Tokyo, case re<br />
ports appeared from various localities in this country. As a whole, in the north<br />
of Chyugoku area it is rarely found, fairly many in number in Kyushu area<br />
and as high as nearly 10 per cent on such southern islands of Kyushu as Yaku,<br />
Tanegashima, Amami Islands and Ryukyu Islands. Reports now available were<br />
presented as following from northern localities.<br />
SASA, HAY ASHI, TANAKA et at. (1957) found at the examinations of coal<br />
miners in Hokkaido area 2 out of 448 in Chashinai and 1 out of 808 in<br />
Ashibetsu.<br />
T AKEKA w A, SUGANUMA and EN DO (1958) reported at the examinations of coal<br />
miners in Fukushima Prefecture 8/404 (1.98%) at Jyoban mine, Yumotobe and<br />
6/119 (5.04%) at Taisyo mine, Nakoso City.<br />
MATSUBA Y ASHI (1951) and OSADA (1952) found 3 cases among 395 pupils of<br />
a middle school at Izumi Village, Shioya Gun, Tochigi Prefecture, and obser<br />
ving those three families consisted of 9, 5, and 7 persons respectively, all 17<br />
persons among 21 except children younger than 9 years old were found to be<br />
carriers. Those three families neither contacted each other nor had possible<br />
common root of infection and were independent dense infection in each family.<br />
In Tokyo, a case reported by HATORI (1898) and another case by KUROKAWA<br />
(1951) were known, but the source of infection was not clarified. The other<br />
cases found in Tokyo were mostly people from Amami and Ryukyu Islands.<br />
SUGANUMA (1958) reported a case among 49 farmers in the suburbs of<br />
Yokohama City.<br />
MIYOSHI & UCHINO (1951) examined 10,281 school children, from kindergardens
to high schools, at coal mine villages of Ube, Onoda and Shimonoseki Cities<br />
in Yamaguchi Prefecture, and found 2 cases out of 10,281. KAWAMOTO (MIYOSHI<br />
and UCHINO, 1951) also expressed that strongyloidiasis was not rare at mining<br />
areas of Ube City.<br />
In the northern Kyushu, TASHIRO (1912 a, b) described a case in Yatsushiro<br />
and 12 cases out of 265 coal miners, 11 having come from Kumamoto Prefec<br />
ture and 1 from Saga. SHIMURA (1918) in his study observed several cases in<br />
Saga Prefecture, and Iw A Y A (1914) reported a few cases from Goto Islands,<br />
Nagasaki Prefecture. SATO, S. (1932) and MISAO (1941) treated the cases from<br />
Fukuoka Prefecture, MIYAZAKI (1947) recorded 3/382 (0.8%) among school children<br />
near Yatsushiro City and SASA, HAYASHI, TANAKA et ai. (1957) detected the 3<br />
cases out of 10,182 coal miners in the northern Kyushu.<br />
In Miyazaki Prefecture, MIYAZAKI (1947) found 0.1%, UCHIZONO (1954) 6 cases<br />
out of 1.000 people in Nichinan City and Nagayoshi 1 case among 956 outpatients<br />
in Fukushima Town, Minaminaka Gun.<br />
In Kagoshima Prefecture, MIYAZAKI (1947) reported a case from Nishisakura<br />
zima Village, 4 cases in Kanoya City among 3,175 school children. UENO (1948)<br />
found a case in Komenotsu Town and TERASHI (1953) 19/3,809 among school<br />
children in Oguchi City. ABE (FUKUSHIMA & YAMASHITA, 1955) reported in<br />
Kagoshima City 1/117 in Jimpu dormitory, 4/275 in deaf school children, 1/645<br />
in Ushyuku school, 1/1,255 Jissen Girls' High School and ODAWARA (1954)<br />
recorded a fatal case. Fukushima observed a case on Shishi Island, Higashinagashima<br />
Village and TERASHI & NAKAMURA (1954) reported 0.5% positive rate<br />
at Isa Gun.<br />
Y AMASHIT A recorded 2/19 among school children and 12/44 among the<br />
dwellers on Yaku Island, and NAGOE & YONEZAWA (1954) treated several cases<br />
on Tanegashima Island.<br />
On Amami Oshima Island, FUKUSHIMA & YAMASHITA (1955) found 18/1,320<br />
(1.36%) in primate and middle school and 5/519 (0.96%) in the dwellers. TAN AKA<br />
(1957 b, 58) reported on the same island 28/3,741 (0.83%) in school children 5 to<br />
18 years of age and 53/721 (7.4%) in the dwellers of Setouchi Town. SASA et<br />
at. (1958) using the smear and test tube cultivation techniques detected 6/423<br />
(1.42%) in the Asahi primary school, Naze City and 42/1,583 (2.72%) among the<br />
dwellers.<br />
Island.<br />
KOGA (1955) found 42/1,583 (2.72%) among the dwellers on Tokunoshima<br />
In Okinawa Island, SHIROMA (1956) detected 116/2,026 (5 .7%) among primary<br />
and middle school children near Yonabaru Town, SHIROMA (1959) also 129/1.361<br />
(9.5%) in outpatients at the same locality and SASA, TERUYA et at. (1958) 138/1,250<br />
611
612<br />
(11.0%) in the dwellers at farming villages of the southern Okinawa.<br />
TANAKA, KUMADA et al. (1959) recorded 38/744 (5.7%) on Miyako Island, and<br />
YOSHINO (1932, 39) observed and treated numbers of cases of strongyloidiasis on<br />
Ishigaki, Yaeyama Islands.<br />
B. Distribution in the Epidemic Foci<br />
In Amami and Ryukyu Islands, the epidemic foci of strongyloidiasis are<br />
widely spreading but the positive rates differ widely among villages, as reported<br />
0-17.8% in Amami Oshima Island (TANAKA, 1957 b), 2.0- 23.6% in Okinawa (SASA<br />
et al. 1958) and 4.6-17.9% in Okinawa (SHIROMA, 1959).<br />
In Amami Oshima, shight difference in age was proved by TANAKA (1957)<br />
but in Okinawa, positive rates elevates in older age groups (SASA et al., 1958,<br />
SHIROMA, 1959). In Miyako Island, the highest peak of the positive rate was<br />
seen at 5 to 9 age group (TANAKA, KUMADA et al., 1959). In the examination<br />
of SHIROMA (1959), positive rate was higher in man than in woman.<br />
In the results reported by SATO, S. (1932) and OSADA (1952), many persons<br />
in a family suffered and serious infection seemed to occur inside a family.<br />
Though those cases of the serious family invasion were often met in the epidemic<br />
foci, proof could be little obtained for family accumulation of the Strongyloides<br />
infection in the statistical examinations made by SASA, HAYASHI et al. (1958 )<br />
and TANAKA, KUMADA et al. (1959).<br />
When correlating infection of Strongy.loides with other nematodes was statisti<br />
cally examined from the record of SASA, TERUYA et al., the correlation exists<br />
closely between Strongyloides and Necator americanus and fairly with Ancylostoma<br />
duodenale and Trichuris trichiura.<br />
IX. HUMAN STRONGYLOIDIASIS<br />
A. Early Reports of this Country<br />
Of all available reports, the first one may be the case observed by HATORI<br />
(1898). The patient, a vagabond, was forced to be isolated into the Komagome<br />
Hospital, being assumed as a patient of dysenteria, and neither bacteria, nor<br />
amoeba was found from stool. In the further fecal examinations the correct<br />
diagnosis was made detecting the larvae of Strongyloides and clearly distinguishing<br />
from the larvae of hookworms and other free living nematodes. The
symptoms of the patient were diarrhea, tenesmusm severe emaciation and the<br />
patient died and autopsyed after 100 days due to obstinate inappetency, bloody<br />
mucous discharge and emaciation.<br />
After the report above mentioned, records of case study were published by<br />
NAGASAWA (1902), KIMATA (1903), YAMADA (1907), HASEGAWA & CHIKADA (1903)<br />
SHIGA (1909), IMAIZUMI (1911), TASHIRO (1912) and IWAY A (1912). OHIRA (1913, 14)<br />
published his opinion that false identification was enclosed mostly in the early<br />
records of Strongyloides besides that made by HATORI (1898). But in the recent<br />
re-examinations through those originals, correct strongyloidiasis was seen in a<br />
part of the cases of Iw AY A (1912) and in all cases reported by TASHIRO (1912).<br />
Since 1914, any false identification has scarcely been seen in most papers in this<br />
country.<br />
B. Clinical Manifestations<br />
1. Incubation period<br />
In the experiment of human infection of S. stercoralis made by TANAKA<br />
(1957 d), symptoms of the respiratory organs appeared after 6 days and the larvae<br />
were found in stool after 27 days, using the smear method. In the experiment<br />
with dogs and S. stercoralis, the period was 16 days at minimum by TASHIRO<br />
(1912 b), 5 to 7 days by NISHIGORI (1928) and 10 days by FAUST (1933) respectively<br />
and all the results seemed to be comparatively short.<br />
2. Early symptoms<br />
The human experimental infection was successfully made by TANAKA<br />
(1957 d, 58) applying 300 larvae with cultivation medium for 2 hours on the<br />
palmer side of the forearm. At the inoculating site of the skin, tiny itchy<br />
erruptions appeared at the removal of the medium, enlarged in maximum size<br />
after 9 days like itchy rising erruptions of prurigo and disappeared after 27<br />
days. Cough appeared after 6 days for 3 days, slight tenderness on pharynx,<br />
irritation of the trachea and there occurred such symptoms of the alimentary<br />
tract as abdominal fullness, discharge of the soft stool and uncomfortable inte<br />
stinal irritation after 17 days, watery diarrhea after 19 days, on the contrary<br />
constipation after 23 days and abdominal pain after 24 days. Thus alimentary<br />
symptoms began after 17 days with uncomfortable intestinal irritation and<br />
abdominal fullness developed later to the pain, diarrhea or diarrhea accompanied<br />
with constipation. After 25 days cough appeared again, the larvae were found<br />
first on the 27th day and stubborn inappetency took place. After 32 days slight<br />
dischrge of bloody mucous stool was experienced with cramping pain on the<br />
ileocoecal region. On the 39th day, bloody mucous stool was discharged several<br />
times with tenesmus. Clinical symptoms became severe after 29th day showing<br />
incessant cough, abdominal tenderness, occasional occurrence of the cramping<br />
613
614<br />
pain of the ileocoecal region, diarrhea and stubborn inappetency. The cramping<br />
pain usually occurred in the late evening and lasted for 10 to 30 minutes. The<br />
bloody mucous stool looked homogeneus strawberry jelly without pus and was<br />
discharged immediately after the cramping pain. The alimentary symptoms<br />
reduced and gradually disappeared after administration of diethylcarbamazine.<br />
3. Chronic stage and acute exacerbation<br />
Symptoms of the carriers found at the mass examination and those of the<br />
outpatients of the hospital were mostly in the chronic stage or acute exacerba<br />
tion. Symptoms and occurring cases of 9 carriers examined by FUKUSHIMA &<br />
YAMASHITA (1955) on Amami Oshima Island were diarrhea 6, epigastralgia 8,<br />
anemia 8, pain on the lower abdomen 6, emaciation 5, chest pain 5, edema 5<br />
and cough 4 respectively. In the similar examinations about 37 cases on the<br />
same island, TANAKA (1957 d, 58) reported no symptoms in 6 cases, slight disorder<br />
in 16 and moderate disorder in 15 and symptoms and occurring number were<br />
abdominal pain 17, soft discharge 14, inappetency 9, cough 8, emaciation 8,<br />
bloody mucous discharge 7, borborygmus 6, chest pain 4, constipation 4, edema<br />
4 and vomitting 2 respectively. In the similar observations of MIY AGAMI (1960)<br />
about 60 cases on Amami Oshima and Tokunoshima Island, symptoms and<br />
numbers of cases were soft discharge 48, borborygmus 22, epigastralgia 18,<br />
physical weariness 16, pain on foot 13, anemia 10, inappetency 9, pain on the<br />
right hypochondrium 9, edema 8, constipation 5, pain on the chest 5, cough 4,<br />
oversecretion of saliva 3 and bloody mucous discharge 2 respectively.<br />
SHIROMA (1959) treated 102 cases of outpatients in a clinic of Okinawa Island,<br />
Ryukyu and 67 cases had slight disorders, 23 moderate ones and 12 severe<br />
symptoms by which 7 cases out of the latter 12 cases were dead. Symptoms<br />
and frequency were anemia 40, physical weariness 35, watery diarrhea 32,<br />
epigastralgia 23, abdominal pain besides epigastral region 22, edema 22, palpi<br />
tation 18, emaciation 15, cough 14 and inappetency 7 respectively. Extruding<br />
other symptoms than in strongyloidiasis, the symptoms peculiar to this disease<br />
in high frequency were thought to be watery diarrhea, epigastralgia, emaciation,<br />
cough, vomiting and pain on foot and then the additional disorders accompanied<br />
with the severity of the disease were thought to be inappetency, physical<br />
weariness, edema, anemia and palpitation.<br />
4. Severe cases<br />
YOSHINO (1932) observed 25 patients of severe cases, among which 13 cases<br />
were dead and the cause of the death was expressed as high grade of emacia<br />
tion due to the lasting diarrhea with occasional bloody mucous discharge for<br />
long period of time. Diarrhea occurred at all cases, bloody mucous discharge<br />
in 10 cases and abdominal pains frequently at bot h lower regions in 13 cases
often at the patients with bloody mucous discharge. In two cases, abdominal<br />
pain occurred at the cease of diarrhea and bronchitis presented at 14 cases.<br />
The filariform larvae could be detected from the sputum of two cases and in<br />
a patient rhabditoid larvae and eggs were detected from the sputum during 15<br />
days before his death. This case seems to be the first report in human cases<br />
of the parasitism at the respiratory mucosa. Among 15 severe cases observed<br />
by SHIROMA (1959) alimentary symptoms were remarkable, diarrhea and abdominal<br />
pain existed, cough was mostly complained with physical findings on the<br />
respiratory organs, and high grade emaciation, edema and pain on the legs<br />
were often observed. There were various courses of severe cases, case with<br />
several repetation of the acute exacerbation during long period, one with sudden<br />
emaciation to death in a shorter period, one with hydrothrax, with pneumonia,<br />
pyothorax and with paralitic ileus. In patients whose sputum was examined,<br />
filariform larvae were found in all cases and also rhabditoid larvae and/or eggs<br />
were detected in three cases and the frequent occurrence of the autoinfection<br />
and parasitism in the respiratory tract was clarified in the severe cases.<br />
5. Clinical examinations<br />
SHIROMA (1959) examined hematology in 8 severe cases and 6 moderately<br />
severe cases. As a whole, anemia was remarkable, numbers of red blood corpuscle,<br />
hemoglobin and hemoglobin index were reduced, and leucocytosis with<br />
increase of neutrophilic granulocytes in moderately severe cases and with<br />
reduction of them in severe cases, normal count of monocytes, nuclear shift to<br />
the left were seen. Urobilinogen in the urine presented in the 6 severe cases,<br />
reduction of serum protein, positive Gloss' reaction, slight increase of index of<br />
jaundice, sometimes positive Lugol's reaction in the urine. The positive BSP<br />
reaction in a case out of three were observed and from those results, slight<br />
disorders of the liver were considered. MIYAGAMI (1960) examined 60 cases of<br />
carriers and found anemia with less than 4 million red blood corpuscles in 8<br />
cases, leucocytosis with more than 8,000 leucocytes in 28, reduction of hemoglobin<br />
less than 80% in 41, eosinophilia in hemogram, positive protein in urine in 5<br />
cases each, urobilinogen in urine in 9 and positive Gloss' reaction in a case.<br />
C. Miscellaneous Cases<br />
In many cases, filariform larvae were found in sputum and other organs<br />
as they migrated through various organs. Discovery of filariform larvae in<br />
sputum might be first reported by SHIMURA (1918) and ONODERA (1922), and later<br />
KAW AJI et at. (1956) found filariform larvae, rhabditoid larvae and parasitic<br />
females in the bronchial abscess in an autopsy. ITO (1932), MIYOSHI & UeHINo<br />
(1951) and KAWAJI (1959) detected filariform larvae in the liver and correlating<br />
to those cases, a case with liver cirrhosis was reported by TANI & UZAWA (1954)<br />
615
616<br />
and the complication of ascites was shown by MISAO (1941), TAKAHASHI (1942)<br />
and UMEKI (1951). The larvae also were found from such various organs as<br />
heart muscles by ITO (1932), kidney by MIYOSHI & UCHINO (1951), epirenal cor<br />
puscle and pancreas by ITO (1932) and thyroid gland by KAWAJI et al. (1956 )<br />
respecti vely.<br />
KOGA (MIYOSHI & TAKABAYASHI, 1951) and YOSHINAGA (1950, 51) reported<br />
fatal cases due to the intestinal perforation. SHIMURA & OGAWA (1920 b)<br />
obtained numbers of rhabditoid and filariform larvae from the vomit. In a case<br />
with liver cirrhosis observed by UMEKI (1951) filariform larvae were seen in the<br />
pleural and abdominal effusion. A case reported by ODAW ARA (1952) was<br />
hospitalized with clinical manifestations of anemia, swelling of abdomen,<br />
emaciation and vomiting showed positive reaction of protein in urine and<br />
filariform larvae in the abdominal effusion and died after 1 week. ONODERA<br />
(1922) experienced frequent occurrence of the transcient glycosuria in a patient.<br />
FORNARA (1923) and WHITEHALL et al. (1944) described about the discovery of<br />
the larvae of Strongyloides in the urine, but little proof was clarified in both<br />
reports about the identification of the larvae. The presence of larvae of<br />
Strongyloides in urine is doubtfull from the consideration of the study made by<br />
HAYASHI et al. (1958) who clarified the detection of the larvae of the free living<br />
nematodes in urine of 7 cases. YAMAGUTI (1925) observed petechial bleeding in<br />
cerebrum and cerebellum in dogs with experimental infection.<br />
SHIROMA (1959) and SATO, S. (1932) found a baby patient 11 months old and<br />
12 months old respectively.<br />
TOMITA (1941) experimentally infected S. fulleborni from Macaca cyclopis to<br />
man with success. In four human voluntary infections, no skin reaction occurred,<br />
urticaria appeared within 10 days with fever in 2 cases and eosinophilia was<br />
seen in all cases. Eggs began to be evacuated after 16 to 32 days, reduced in<br />
number after 7 months and were detectable using cultivation technique till 11<br />
months later.<br />
D. Pathological Studies<br />
In coincident with the life cycle, the organs of remarkable changes were<br />
skin as the site of invasion of larvae at infection, duodenum as the lodging<br />
site of the parasitic females, lower portion of the ileum and colon as the site<br />
of internal reinfection and the lungs, liver and parenchymal organs associating<br />
with larval migration.<br />
1. Human autopsies<br />
Human autopsy cases were seen in those reports of OHIRA (1913), SHIMURA<br />
(1918 a), HATANO (1925), KAWASAKI (1924), MATONO (1931), YOSHIDA (1932), MIYOSHI<br />
& TAKABAYASHI (1951) and KAWAJI et al. (1965). In the report of MIYOSHI &
T AKABA Y ASHI (1951) histological pictures were described in all organs and are<br />
thought to be representative descriptions of this disease. The patient was 41<br />
years old coal miner, hospitalized as high grade emaciation due to the 2 years<br />
lasting diarrhea and died after 45 days in the hospital. In autopsy, parasitic<br />
females found were 141 and filariform larvae were detected from intestinal<br />
contents, ascites, pericardial effusion and urine and also found in histological<br />
observation in the stomach, intestinal wall, liver and kidney. Erosion with<br />
bleeding, ulcer and lymphatic follicular proliferation were seen in duodenum,<br />
upper portion of jejunum and rectum, the parasitic females were seen in the<br />
crypt between intestinal epithelium and basal membrane and filariform larvae<br />
in the epitheliar, submucous, muscular, subserous layers and in the lymphatic<br />
nodules. The histological pictures of the invaded portion were the congestion<br />
with infiltration of lymphocytes, plasma cells, histoplasm, polynuclear leucocytes<br />
and eosinophilic leucocytes, and also appearance of the giant cells and dead<br />
filariform vessels were frequently seen in those pathological changes. Congestive<br />
edema and localized pneumonia were seen in the lungs and the larvae in the<br />
alveola, interalveolar connective tissue, capillaries in the alveolar wall, subpleural<br />
lymphatic lumen and in the pneumonial focus. Changes of liver were conges<br />
tion, atrophia of the liver cells, peripheral fatty degeneration, scattering nodules<br />
consisted of lymphocytes, plasma cells, fibroblast and giant cells in parenchym<br />
under liver capsel. Those of kidney were congestion, remarkable bleeding under<br />
capsel and in the renal tubules and turbidity of the tubules, nodules consisted<br />
of lymphocytes and plasma cells, congestion and reticular proliferation in the<br />
connective tissue. The focal catarrh was seen in the mesenterial lymphono<br />
dules and brown atrophia in the heart muscles.<br />
2. Changes in skin<br />
Little report was available about the change of skin in human cases. OSHIO<br />
& F URUTA (1955) observed the invading process of S. ransomi in the skin of<br />
pigs. The invasion of the larvae took place not only at the openning pores of<br />
the skin but also at the cuticular layer directly in histological observation,<br />
inflammation was seen at superficial and profound cutis but not at subcuticular<br />
connective tissue and changes were infiltration of eosinophilic small mononuclear<br />
cells and capillary dilatation but no bleeding existed. Observing the dilatation<br />
of lymphatic vessels, edema and inflammation around the capillaries, the larvae<br />
were considered to invade into the lymphatic vessels along capillaries and small<br />
veins.<br />
3. Changes in the intestinal wall<br />
The change of the lodging portion of the parasitic females appeared in the<br />
several reports since OHIRA (1913). In the report of KAWASAKI (1924), macros-<br />
617
618<br />
copic congesting spots were seen at the mucosa of duodenum, parasitic females<br />
parasitized in the Lieberkiihn's gland on the mucosa of Kerckring's crypts and<br />
hatching rhabditoid larvae presented in the gland and/or in proprial layer and<br />
less in submucosa and none in muscular layers. Surrounding parts of the<br />
parasitic females, infiltration of the small round cells and a little number of<br />
polynuclear leucocytes were found and atrophia of mucosa and defect of villi<br />
at the gathering part of the larvae. In Lieberkiihn's gland, changes were<br />
dilatation of the canal, flattened gland cells, disarrangement and necrosis of<br />
gland cells, increase of collar cells, dilatation of arterioles and infiltration of<br />
small round cells. MATONO (1931 a) experienced the polyposis spread widely at<br />
duodenum in a human autopsy case. TANABE (1939), in experimental infection<br />
of S. ratti in rats, observed the infiltration of eosinophilic cells at the superficial<br />
mucous layer of duodenum after 3 or 4 days since the infection when adult<br />
worms reached duodenum and also found the similar infiltration in the profound<br />
layer after 15 days.<br />
Histological changes of larval reinfection at the lower portion of small<br />
intestines and colon were described by NISHIGORI (1928), using many experi<br />
mental infections on dogs. When considerably many larvae invaded mucosa,<br />
the increase of collar cells, mucous atrophia, epithelliar exfoliation, erosion<br />
and congestion of vessels were seen. And in further developing changes, ulcer<br />
appeared, the base of it penetrating till muscle layers with invading pictures<br />
of filariform and rhabditoid larvae and appearance of leucocytes and pustration<br />
cells. Filariform larvae presented in lymphatic space between the surface and<br />
the muscle layers and changes were found in the infiltration of leucocytes and<br />
dilatation of lymphatic vessels and capillaries. In muscle layers, larvae existing<br />
around lymphatic and blood vessels or nervous fibers, the degeneration of muscle<br />
fibers and cellular infiltration were seen. Larvae invaded into the mesenterial<br />
lymphatic nodes, especially into those at ileocoecal region, destroyed the nodular<br />
parenchym, and dilatation was seen at the peripheral lymphatic vessels.<br />
The changes of larval reinfection examined in human autopsies by TAKEUCHI<br />
(1905), HATANO (1925), KOGA (1951) and YOSHINAGA (1950, 51) were found in the<br />
inflammatry changes at duodenum and the upper portion of small intestines.<br />
And in the reports of OHIRA (1913) and KAWASAKI (1924), multiple ulcers were<br />
seen at ileocoecal region to colon, and also in those of SHIMURA (1918 a), MATONO<br />
(1931) and YOSHIDA (1932) changes were observed at the lower portion of small<br />
intestines to colon. In a case of the study by HATANO (1925), having rhabdomyoma<br />
at the lower portion of small intestines, the larval invasion and changes<br />
were observed at the upper portion above the neoplasma, but none below it.<br />
In a case by KOGA, (MIYOSHI & TAKABAYASHI, 1951), it was observed that a
part of small intestines, 2 meters below the beginning, was edematous, dark<br />
purple brown and perforated in the middle of that area, and filariform and<br />
rhabditoid larvae were invading, till submucosa around the perforation. In a<br />
case reported by YOSHINAGA (1950, 51), 3 parts of small perforation were found<br />
at duodenum and single perforation at intestine, 130 cm below the beginning,<br />
but none at colon.<br />
4. Changes in lungs<br />
KAW AJI et at. (1956) observed in a human case numbers of miliar abscesses<br />
in both lungs, in which larvae and parasitic females were detected, slight<br />
inflammatry and bleeding changes and giant cell nodules in histology. NISHIGORI<br />
(1928) in an experiment with dogs, noticed macroscopic bleeding spots and<br />
maculae in lungs and then found in histology of the parts around larval invasion,<br />
capillary congestion, bleeding, epithelliar exfolliation on bronchioles and<br />
effusion containing larvae pustlation cells, leucocytes and epitheloid cells,<br />
chocking respiratory tract till large bronchus. At thickening alveolar wall,<br />
infiltration of small cells, capillary congestion and nodules consisted of epitheloid<br />
cells and fibroblasts were seen.<br />
5. Pathogenicity<br />
The existence of pathogenicity of this worm had been discussed in the past<br />
years, but neither extreme exaggeration of pathogenicity nor its absence is<br />
dicisively considered in recent years. The appearance of pathogenicity depends<br />
upon the individual physical sensitivity, differs case by case, and not always<br />
parallels with the density of parasitized worms. As various reports clarified,<br />
severe and fatal cases appear only among patients with dense parasitism and<br />
heavily parasitized carriers incline to fall acute exacervation. In observation<br />
of carriers made by TANAKA (1957 d), the severity of symptoms did not correlate<br />
to the density of parasitism, and no age difference was observed about the<br />
severity of symptoms, though children below 15 years old harboured more<br />
worms than older persons. On the other hands, SHIROMA (1959) found severe<br />
cases presented in old men more frequently.<br />
619
620<br />
X. STRONGYLOIDIASIS OF ANIMALS<br />
A. Strongyloides ransomi<br />
This species infesting pigs has short period of days from infection to<br />
maturity. OSHIO & FURUTA (1954) found 5 days old pig evacuated the eggs.<br />
In the experimental infection to pigs, OSHIO (1956) found the evacuation of eggs<br />
after 5 days, and the larvae marked with p 32 appeared in intestines 4 days<br />
after infection.<br />
In the course of egg evacuation followed by FURUTA (1954), numbers of<br />
discharged eggs suddenly increased between 5 to 10 days after infection till<br />
maximum and reduced immediately to 1/10 of the maximum value after 40<br />
days. From the mass examination of pigs made by WATANABE (1956), pigs<br />
were infected naturally immediately after birth, the ratio of infections reached<br />
100% after 1 month, and then positive rate was reduced approximately to 50%<br />
after 8 months. The discharge of eggs increased suddenly till the end of the<br />
1st month, 12,000 E. P. G. in an average, then suddenly lowered approximately<br />
to 3,000 after 2 months, less than 100 after 4 months and kept the same condi<br />
tion after 7 months. OSHIO & FURUTA (1954) reported the discharged eggs were<br />
more in number in the pigs of spring birth.<br />
WATANABE (1956) examined relationship between evacuation number of eggs<br />
and symptoms, and described the pigs in less than 50,000 E. P. G. had no clinical<br />
symptoms, those in more than 100,000 E. P. G. showed inappetency, discharge<br />
of soft feces and delay of growth and those in more than 1 million E. P. G. fall<br />
into malnutrition, took only water and died within 10 days.<br />
From the studies of treatment made by NAKAJIMA (1955), WATANABE (1956)<br />
and OSHIO & TAKAHASHI (1958), gentian violet has been used effectively in<br />
practice. For the protection of infection, WATANABE (1956) suggested the construction<br />
of the concrete made stall with dried environment and OSHIO &<br />
TAKAHASHI (1958) advised the diminish of the infective larvae from the stall by<br />
spraying BHC dust.<br />
B. Strongyloides ratti<br />
1. Detecting method<br />
Though the detection of Strongyloides ratti has been hitherto made by
obtaining parasitic females from the intestines, TANAKA, AMANO et al. (1959)<br />
constructed the simple method of detection applying stool examinations. Eggs<br />
were found in the smear technique and the floatation technique in satulated<br />
brine solution and filariform larvae in the test tube cultivation technique, but<br />
differential identification was needed from those of Nippostrongylus brasiliensis<br />
(TRAVASSOS, 1914) in either methods. Comparison of detecting counts of eggs<br />
or larvae was made among the three different techniques, smear, floatation and<br />
cultivation, using 13 samples of feces and averages of counts were 17.0 in 3<br />
smears, each containing 10 mg feces, 60.7 in 3 hold floatation technique each<br />
100 mg and 217.9 in the three test tube cultivations each 300 mg, consequently<br />
the cultivation techuique was most satisfactory. In comparison of cultivating<br />
conditions made by TANAKA & AMANO (1958), AMANO (1959), the optimum condition<br />
was the incubation at 26°C. for 3 to 6 days.<br />
2. Distribution<br />
AMANO, KANO & TANAKA (1958) and AMANO (1959) examined infestation<br />
among Rattus norvegicus and Rattus rattus in Tokyo, using fecal examination<br />
and positive rates of S. ratti were 62.5% in 280 R. norvegicus and 13.3% in 98<br />
R. rattus. On the other hand, detecting the parasitic females of this species,<br />
TANABE & T AKEISHI (1936) found 66.9% positive among R. norvegicus in Tokyo,<br />
NISHIMURA (1943) 54.9% in Fukuoka and MIYAZAKI (1946) 44.0% in Kagoshima<br />
respectively. ABE et al. (1960) examined in surrounding areas of Kagoshima City<br />
and on Tokunoshima Island, rates were 51.7% in R. norvegicus and 26.3% in R.<br />
rattus. In both studies of AMANO et al. (1958) and ABE et al. (1960), no sex<br />
difference existed and the higher rates were found in the groups of heavy<br />
body weight.<br />
3. Experimental infection to laboratory rats<br />
TANABE (1939) injected the infective larvae of S. ratti subcutaneously and<br />
observed the period of appearance at digestive tract and lodging portion. No<br />
worm was found in intestines till the end of 48 hours, a few worms in the<br />
stomach and intestines after 60 hours, and after 72 hours two each in oesophagus<br />
and in stomach, 802 in the first 1/4 part of intestine, 2 in the second 1/4 part<br />
and a few in lower half part. TANABE (1939) also infected 9 rats, and found<br />
the beginning of egg evacuation after 4 days in 4 rats, and 5 days in 5 rats,<br />
and evacuation was lasting for 87 to 126 days.<br />
TANAKA & AMANO (1959) and AMANO (1959) infected 5 rats applying 500<br />
larvae subcutaneously, evacuation of eggs began after 6 days in 3 rats and 7<br />
days in 6 rats. In the quantitative measurement of evacuation with the test<br />
tube cultivation technique, the count amounted to reached the maximum after<br />
10 to 15 days, became only a few after 40 days, then lasted in a few number<br />
621
28 °C. , 75 hours at 24°C., 100 hours at 19°C., 200 hours at 11-15°C. respectively,<br />
and no development of eggs appeared at the temperature lower than 7°C. and<br />
higher than 41 °C.<br />
The optimum condition for the cultivation of the free living phase with<br />
stool examined by TANABE (1938 d) was yielded by the method using the medium<br />
of 5 g. of finely smashed stool and 20 cc water deposited into a Petri dish 3 mm<br />
in depth and under the excellent ventilation. In comparison of the culturing<br />
temperature, the average numbers of the larvae available from the same fecal<br />
examples were 0.8 at 3TC., 264.2 at 32 °C., 889.7 at 28°C., 712.4 at 24°C., 407 at<br />
20°C., 65 at 11-15°C. respectively and the temperature between 24-28 °C. was the<br />
optimum condition of the temperature which was considered to be somewhat<br />
lower than that measured in S. stercoralis by TANAKA, TOKURIKI et al. (1958).<br />
Little influence was seen at the pH between 6.8-8.6 to the development of larvae.<br />
TANABE (1938 b) observed the rates of directly developing larvae and indi<br />
rectly developing adult worms on large numbers of cultures. The rates of<br />
apperance of indirect development were 1/130-1/821, 1/7-1/824, 1/7-1/2,119 and<br />
1/52-1/169 in four strains, and showed wide deviations but little influence could<br />
be effected by the environmental conditions.<br />
A. Reports of Anthelmintic Studies<br />
1. On S. stercoralis<br />
XI. TREATMENT<br />
Numbers of chemicals have been hitherto tested and applied to the treatment<br />
of the human strongyloidiasis. The first report in this country was made<br />
by TASHIRO (1912 b) who applied peroral administrations of Lugol's solution,<br />
quinine hydrochloride and atoxil in vein. NISHIGORI (1928) clarified the disadvantage<br />
of use of constipating medicine, especially of bismus subnitricum, to<br />
the diarrhea of this disease from the experiment with dogs, because constipating<br />
medicine promoted heavy autoinfection. From this standpoit, YOKOGAWA (1929)<br />
recommended the lasting administration of mild purge, Laxatol 0.5 g with<br />
sulphur powder 1.0-1.3 g daily. As the result, in a case, larvae came to reduce<br />
after 3 months, almost disappeared after 8 months and diminished after a<br />
year.<br />
623
624<br />
YOSHINO (1939) studied the application of gentian violet successfully in seve<br />
ral cases as described below. MISAO (1941) observed no activity on Yatren, and<br />
by the use of 4% emetin hydrochloride 1 cc daily for 6 days and 2 cc daily for<br />
6 successive days in a case, larvae diminished and a parasitic female was dis<br />
charged. MORI & KURODA (1948) proved disapperance of larvae using gentian<br />
violet in a dosis 60 mg three times a day totaling 3.3 g, and also KISHIDA &<br />
HONMA (1952) with gentian violet 150 mg three times a day for two days, and<br />
two hold injection of Stibnal and found negative after 14 days with the detec<br />
tion of the concentration technique of centrifugalization. TERASHI & NAKAMURA<br />
(1954) expressed value of thymol, neglecting the effect of gentian violet. NAGOE<br />
(1954) applying carbarsone found the diminish of the larvae in a case and<br />
proved valuable application to the symptomatical treatment in several cases.<br />
TANAKA (1957 d) observed gentian violet had effect enormously to reduce the<br />
larvae and diethylcarbamazine had slight anthelminthic effect though it eased<br />
clinical manifestations of the alimentary tract as a symptomatical medicine.<br />
SAITO et ai. (1959) failed to treat with piperazine chemicals, I -bromonaphthol<br />
(2), emetin hydrochloride, Stibunal and Yatren, and successfully treated with<br />
gentian violet in a dosis 180 mg daily for 6 days totaling 3.6 g. SHIROMA<br />
(1959) testing numbers of chemicals found no anthelmintic effect on carbarsone,<br />
ethylen tetrachloride, I -bromonaphthol (2), piperazine chemicals, Stibunal,<br />
Fuadin. Atebrin and diethylcarbamazine, much satisfactory effect on gentian<br />
violet and symptomatical effect on carbarsone, and further clarified the admini<br />
stration of constipating medicine for short period did not promote the severity<br />
of strongyloidiasis, rather aided to complete the succeeding anthelmintic treat<br />
ment. Treatment with dithiazanine originated by Sw ARZWELDER et ai. (1958)<br />
was studied by MORISITA, T., KOBAYASHI et al. (1959) and by FUKUSHIMA &<br />
TSUKASA (1960) with successful results. The anthelmintic effects and the rela<br />
tionship among effect, side reaction, coating type of tablets and method of<br />
application were clarified on gentian violet by SHIROMA (1959) and TANAKA,<br />
SHIROMA et al. (1960) and also on dithiazanine by TANAKA, SHIROMA and AMANO<br />
(1960).<br />
Studies on the anthelmintics of S. stercora lis were also made using experi<br />
mentally infected dogs. On the experiments of numbers of such infected dogs,<br />
SATO, S. (1933 b) found no anthelmintic effect on the injection of Fuadin in a<br />
dosis 0.05-0.1 cc per 1 kg body weight neither on the administration of oleum<br />
chenopodii and Yatren. Slight activity was proved on the peroral administra<br />
tion of Livanol and remarkable effect on gentian violet in a dosis 20-30 mg per<br />
1 kg body weight but the effect was reduced in a dosis 10 mg per kg and less<br />
in 5 mg per kg.
626<br />
after certain days from administration and the period was 4 to 6 days in the<br />
report of YOSHINO (1939) and 3 to 6 days in that of TANAKA, SHIROMA et al.<br />
(1960). The course of larval counts in the treatment of a case, for example,<br />
shown in TANAKA et al. (1960) was that the larvae were 470.2 in a smear speci<br />
men in an average at beginning and succeeding daily counts after treatment<br />
were 600.9, 204.2, 14.3, 0.2, 0, 0 respectively.<br />
YOSHINO (1939) found the parasitic females evacuated in the stool in a course<br />
of the treatment with gentian violet in 4 cases out of 16 and TANAKA, SHIROMA<br />
et al. (1960) also observed the evacuated parasitic females. The evacuation was<br />
seen from the next day to 7 days after administration. The maximum count<br />
of evacuated parasitic females observed by TANAKA, SHIROMA et al. (1960) was<br />
7.0 in a smear specimen in an average, the daily counts of this case were 0.5,<br />
3.0, 7.0, 3.0, 1.0 respectively and total evacuation in this period was calculated<br />
as much as 290,000. The output of filariform larvae in sputum was measured<br />
by YOSHINO (1939) in the course of treatment and the count in a case were 176<br />
in a smear specimen before treatment and the daily counts after treatment<br />
were 103, 117, 148, suddenly reduced after 4 days till 9, 55, 1, 1, 0, 0 respectively.<br />
As mentioned above, from the fact that the parasitic females were evacuated<br />
and larvae in stool and also in sputum were reduced by the administration of<br />
gentian violet, no doubt exists on the anthelmintic effect of this medicine.<br />
Nevertheless sometimes eradication was failed applying gentian violet. To<br />
clarify the cause of the failure, SHIROMA (1959) and TANAKA, SHIROMA et al.<br />
(1960) made the comparative studies on the effects of the different types of tablet<br />
and that of the time of administration. Tablets used were three different types<br />
(marking L, M, M ') and administered at different times, 30 minutes before meal,<br />
immediately after meal and 30 minutes after meal. The most effective result<br />
was attained when tal bet M was administered immediately after meal with<br />
success in all 20 cases and the administration of tablet L at 30 minutes after<br />
meal was the least with success of 1 case out of 8. On the contrary, the side<br />
reaction was most severe on tablet M immediately after meal, appearing in 11<br />
cases out of 20 and none on tablet L. In the dissolving test of those three<br />
tablets (according to the 6th supp. of J. P. 1955 and U. S. P. XV) tablet M was<br />
thinnest and the others were thicker. In the report of YOSHINO (1939) who used<br />
gentian violet in the gelatin capsels, the side reactions, inappetency, nausea<br />
and vomiting, appeared in almost half examinees and the drug was considered<br />
to be released from a capsel still in stomach and this early release of medicine<br />
was the cause of successfull results. In consideration from the results of above<br />
experiments, it seems to be difficult to make a such ideal kind of tablet which<br />
releases contents at duodenum, the site of lodgement of S. stercoralis and at the
same time is always compact in stomach to reduce the side reactions. In<br />
practise, the satisfactory results can not be expected unless such thinner coated<br />
tablet may be applied as is definitely dissolved before the beginning of<br />
duodenum even if side reaction of stomach appears.<br />
Gentian violet has been applied to the treatment of S. ransomi of pigs.<br />
NAKAJIMA (1955) administered 1 g daily divided into three times for two days<br />
to 50 young pigs, successfull rate was 90 per cent after 5 to 10 days and pigs<br />
well developed. WATANABE (1956) used 0.6 g daily divided into three times for<br />
two days in 30 pigs, egg diminished in all cases even in animals that discharged<br />
eggs in a concentration more than 1,000,000 E. P. G. and proved its activity.<br />
The drug was administered usually in form of powder or tablets with food but<br />
when pigs could not take any food due to severe strongyloidiasis, mixture in<br />
milk was used or forced administration of the above mixture was tried by<br />
using a pipet. In the experiment of OSHIO & TAKAHASHI (1958), eggs diminished<br />
or enormously reduced in a dosis 0.01 to 0.017 g per kg body weight perdiem<br />
once a week lasting four weeks, or by a single dosis of 0.021 to 0.05 g per kg,<br />
the eggs became negative after 5 days. In the administration of larger volume<br />
than 0.021 g per kg, side reactions, diarrhea, weariness, vomiting, emaciation<br />
and inappetency were much observed.<br />
2. Dithiazanine<br />
SWARZWELDER et ai. (1957, 58) and FRYE et ai. (1957) used dithiazanine and<br />
observed the diminish of larvae in 89 per cent among 18 human strongyloidiasis.<br />
MORISITA, T., KOBAYASHI et ai. (1959) administered 600 mg daily to 5 cases of<br />
heavily infected patient, and larvae became negative within 3 days and also to<br />
26 cases of carriers successful rate was 88 per cent within 13 days. FUKUSHIMA<br />
& TSUKASA (1960) examined 51 cases using dithiazanine, negative by the stool<br />
examination was 91.6 per cent and that by examination of duodenal fluid was<br />
100 per cent. GOTO et ai. (1960) treated with success applying 200 mg three<br />
times a day for 21 days. Stool was examined using the centrifugal concentra<br />
tion technique and filter paper cultivation technique in the whole course, they<br />
observed the cultivations were always negative during the administering period<br />
and considered dithiazanine had a larvicidal activity.<br />
TANAKA, SHIROMA & AMANO (1960) examined application of this medicine<br />
similar to gentian violet. By the administration of dithiazanine, the larvae<br />
were reduced and the parasitic females were evacuated as by that of gentian<br />
violet and the drug was clarified to be satisfactory anthelminthics. As in the<br />
tests, failure was experienced in certain occasions, comparative study was<br />
made on the improved method of application of different types of tablets.<br />
Tablets used had three types (marking L, EA, EB) and coating of tablet was<br />
627
628<br />
thinnest in L and thickest in EB at the dissolving test for enteric coating. The<br />
course of treatment was divided in four types, i) reduction of larvae and<br />
evacuation of parasitic females, ii) reduction of larvae only, iii) transient<br />
reduction of larvae and increase after cease of administration, iv) no alteration<br />
of larval output. When the course of i and ii was successful, the effective<br />
cases/ examined numbers in different tablets and in different daily dosis were<br />
2/4 in L 300 mg, 0/2 in L 600 mg, 1/4 in EA 300 mg, 7/9 in EA 600 mg, and 1/3 in<br />
EB 600 mg. From the result, application of EA tablet 600 mg daily was most<br />
satisfactory and larvae became negative in 6 cases. Side reaction appeared in<br />
the one third of the patients and nausea or vomiting presented the more, when<br />
the thinner coated tablet was used. As pointed out by KOBAYASHI (1959) the<br />
medicine has larvicidal activity, the larvae came to be killed in 80 to 90 per<br />
cent in staines stool at 4 hours after evacuation and in all after 10 hours. So<br />
the detection of larvae from the stool of the patient being treated with dithiazanine<br />
is difficult because dead larva has to be often detected and should be<br />
made with much care even if either the technique of detection might be used.<br />
The exact existance of larvae should be known by the detection on the several<br />
days after the cease of the administration. Similar to gentian violet, it seems<br />
to be difficult to make such a kind of tablet with dithiazanine as keeping<br />
satisfactory anthelmintic effect and simultaneously showing less side reaction<br />
on stomach.<br />
3. The other chemicals<br />
NAGOE (1954) and NAGOE & YONEZAWA (1954) observed disapperance of larva<br />
in a case using carbarsone and symptomatical recovery in other cases. SHIROMA<br />
(1959) also proved symptomatical effect on the severe cases and for the recovery<br />
of the alimentary tract, succeeding administration of gentian violet could be<br />
readily accomplished.<br />
SOTOLONGO (1950) used diethylcarbamazine to three cases with success.<br />
TANAKA (1957 d, 58) administered it to 8 cases in a dosis 4.8 to 11.5 mg per kg<br />
body weight daily for two weeks and the larvae was 14.6 in a smear specimen<br />
in an average at the beginning, 4.8 after a week and 7.2 after 2 weeks. The<br />
reduction was lesser than in gentian violet in control group, in which larvae<br />
were 14.3 at beginning and 0.9 after a week. On the other hand, the medicine<br />
dramatically eased such symptoms as abdominal pain, diarrhea, inappetency<br />
and bloody mucous discharge. The medicine also recovered symptoms of ali<br />
mentary tract on the other 6 cases. FUJITA & TAKAHASHI (1953) administered<br />
diethylcarbamazine in a dosis 30 mg per kg body weight for three days to 81<br />
pigs, younger than 4 months old and harbouring S. ransomi, and development<br />
of body weight was larger than untreated control group though the egg output
was not reduced comparing with controls.<br />
GRAHAM (1960) administered pyrvinium pamoate to Macaca mulatta to prevent<br />
S. fiilleborni and reported successfull result. METZEL (1963) observed the<br />
parasitic femal evacuated into the stool by the administration of pyrvinium<br />
chloride in a child case. The application of pyrvinium chemicals to man was<br />
also reported by BROWN & STERMAN (1958), MEIRA, NETO & CAMPOS (1961),<br />
MEZZOTTI (1959) and WAGNER (1963). Recently TANAKA (1964) applied the suspension<br />
of pyrvinium pamoate in a dosis 5 mg base per 1 kg body weight once<br />
daily for 5 days in two heavily parasitized patients, the larvae suddenly disap<br />
peared within 5 days and complete recovery followed after 2 months. The drug<br />
showed little side reaction and the anthelmintic activity will be much expected<br />
in the further studies.<br />
REFERENCES<br />
l. ABE, Y., N. KAGEl, E. HORI , T. KAWAMOTO, S. MIYAGAMI, M. TAGAWA, T. MUKAI,<br />
S. ARIKAWA, S. TAKEUCHI, T . NISHIDA & Y. ARIKAWA (1960): Studies on Stl'ongyloides<br />
and strongyloidiasis (S-4). Distribution of Stl'ongyloides ratti SANDGROUND, 1925 among<br />
house rats in the south Kyushu. Kagoshima Igalm Zasshi, 33 (11, 12), 1812- 1818. (in<br />
Japanese with English summary)<br />
2. AIZAWA (1910) : Studies on A nguillula intestinalis as a causative agent of chronic<br />
emaciation. juntendo Iji Kenllyulwi Zasshi, (446), 28. (in Japanese)<br />
3. AMANO, R. (1959): Studies on the screening test for anthelmintics on strongyloidiasis<br />
of rats. I) The distribution of St1'Ongyloides ratti among house rats in Tokyo. II) The<br />
course of the daily output of eggs of Strongyloides ratti in experimental infection of<br />
albino rats. III) Comparative studies on anthelmintic effect of several kinds of chemi,<br />
cals. Ochanomizu Igaku Zasshi, 7 (6), 1478- 1500. (in Japanese with English summary)<br />
4. AMANO, R., H. MIZUNO, H. TANGE & H. TANAKA (1959) : The daily course of the<br />
infesting number of Strongyloides ratti after experimental infection in albino rats. Ibid. ,<br />
7 (10), 2928-2931. (in Japanese with English summary)<br />
5. AMANO, R., H . TANAKA & R. KANO (1959) : Screening test for anthelmintics on<br />
S trongzloides applying Stl'ongyloides ratti, Kiseichugaku Zasshi, 8 (3), 412. (in Japanese)<br />
6. ASKANAZY, M. (1900): Ueber Art und Zweck der Invasion der Anguillula intestinalis<br />
in die Darmwand. Zent1'bl. Bakt., 27 , 569- 578.<br />
7. BAVAY, A. (1876): Sur l'anguillule stercorale. Compt. rend. A cad. Sci. Pm'is., 83 , 694-<br />
696.<br />
8. (1877) : Sur l'anguillule intestinale, nouveau ver nematoide, trouve per<br />
Normand chez les malades atteints de diarrhee de Cochinchine. Compt. rend. hebdom.<br />
des seances de I' Acad. sci., 74, 166.<br />
9. BEACH, T. D. (1936): Studies on the free·living phase of the life cycle of St1'ongyloides<br />
(Nematoda). Am. jour. Hyg., 23, 243-277.<br />
10. CHANDLER, A. C. (1925): The species of Strongyloides. Parasitology, 17 (4), 426- 433.<br />
11. CHUJYO, G. (1930) : On the diarrhea due to Stl'ongyloides stel·coralis. Shim'yo, 2 (2).<br />
(in Japanese)<br />
12. DE LANGEN, C. D. (1928): Anguilosis en het ziektebeeld von de "Idiopathische Hypereosinophilie<br />
". Geneesk. T ijdscll1'. v. Nedel'· Indie, 68 (7).<br />
13. DESPORTES, C. (1945): Sur Stl'ongyloides stercoralis (BAVAY, 1976) et sur les Strongyloides<br />
629
630<br />
de primates. Ann. Pamsit., 20 (3, 4) 160- 190.<br />
14. FAusT, E . C. (1930): Gentian violet therapy for Strongyloides infection. International<br />
Med. Digest., 11, 57-58.<br />
15. (1932): The symptomatology, diagnosis and treatment of Stl'ongyloides infec·<br />
tion. ]. A . M. A., 98 (26), 2276-2277.<br />
16. (1933): Experimental studies on human and primate species of Strongyloides<br />
II) The development of Stl'ongyloides on the experimental host. Am. jour. Hyg., 18,<br />
114- 132.<br />
17. FUJITA, J . (1938): Strongyloides papatosus WADL, 1856 obtained from sheep. Nippon<br />
juigallllai Zasshi, 11 (2), 152-169. (in Japanese)<br />
18. & M. TAKAHASHI (1953): Anthelmintic examination of diethylcarbamazine<br />
to Strongyloides mnsomi. jui ChillUsan Shinpo, (124), 1137- 1142. (in Japanese)<br />
19. FUKUSHIMA, H. & S. TSUKASA (1960): Clinical studies on human strongyloidiasis.<br />
KiseichugallU Zasshi, 9 (4), 363-364. (in Japanese)<br />
20. & H. YAMASHITA (1955): Studies on strongyloidiasis in the islands of Amami<br />
Oshima. Kagoshima Daigalzu Igallu Zasshi, 7 (2) supp. 146- 150. (in Japanese with<br />
English sunmary)<br />
21. FULLEBORN, F. (1914): Untersuchung tiber dem Infektionsweg bei Strongyloides und<br />
Ankylostomum und die Biologie beiden Parasiten. A,'ch. Schif. Trop. Hyg., 18 Beiheft,<br />
5, 26-80.<br />
22. GALLIARD, H. (1943): Biological and pathological studies on Strongyloides ste1"Comlis.<br />
Nippon Iji Shinpo, (1102), 2008- 2009. (in Japanese)<br />
23. (1951): Recherches sur l'infestation experimentale a St"ongyloides stel'coralis<br />
au Tonkin (3 note). Ann. de Parasit., 26 (3), 201-227.<br />
24. GONDO, T . (1950): Effect of various kinds of chemicals to nematode larvae. 1) Ascaris,<br />
2) Stl'ongyloides. Osalw lila Daigallu Zasshi, 11 (2), 51. (in Japanese with English<br />
sunmary)<br />
25. GOTO, T., H. MURAMATSU, T . ISHIZAKI & M. KUMADA (1960): A. case study on the<br />
treatment of strongyloidiasis with dithiazanine. Rinsho Nailw Syonika, 15 (12), 1273-<br />
1276. (in Japanese)<br />
26. GRAHAM, G. L. (1938): Studies on St"ongyloides II. Homogonic and heterogonic progeny<br />
of the single, homogonically derived S. mtti parasite. Am. jour. Hyg., 27, 221- 234.<br />
27. HARADA, Y. & O. MORI (1952): Diagnosis of ancylostomiasis with cultivation method<br />
and skin test. Rinshyo Igallu, 37 (3), 219- 223. (in Japanese)<br />
28. HASEGAWA, T. (1924): On the filariform larvae of SI1'ongyloides stercomlis outside of<br />
the host body. Tolzyo Iji Shinshi, (2373), 1134- 1146. (in Japanese)<br />
29. (1927): Strongyloidiasis ste1'Comlis. Shindan to Chiryo, 14 (6), 816- 822. (in<br />
Japanese)<br />
30. & I. CHIKADA (1908): On Anguillula stercomlis obtained from a human<br />
case. Tollyo Iji Shinshi, (1584), 1926- 1929. (in Japanese)<br />
31. HATORI , J . (1898): On the larvae of Stl'ongyloides stercomlis. Tolzyo Igaldwi Zasshi,<br />
12 (16), 735-748. (in Japanese)<br />
32. HAYASHI, S., M. SASA, R. SHIRASA KA, A. TAKA DA, S. OTANI, K. F UKAYA, Y. SUGIMOTO<br />
& Y. YOSHITAKE (1958) : Studies on an outbreak of urinary nematodiasis due to Rhabditis<br />
sp. Kiseichugallu Zasshi, 7 (6), 641-645. (in Japanese) (with English summary)<br />
33. IMAI, T. & G. KOGA (1949): Diarrhea. Rinshyo to Kenllyu, 26 (12), 802- 804. (in<br />
Japanese)<br />
34. IMAlZUMI, K. (1911): A case of Anguillula intestinalis. Iji Shimbun, (826), 433- 434.<br />
(in Japanese)<br />
35. INATOMI, S., D . SAKUMOTO, K . ITANO & H. TANAKA (1963): Studies on the submicro·<br />
scopic structure of body surface of larval nematodes. Kiseichugalm Zasshi, 12 (1), 16-39.<br />
(in Japanese with English summary)
36. ITO, S. (1932): Supplemental studies on parasitic females, eggs and larvae of Strongyloides<br />
stercomlis. Keio Igaku, 12 (11), 2147-2164. (in Japanese)<br />
37. IWAYA, S. (1912): A case of Anguillula intestinalis. Kenyokai Zasshi, 104. (in<br />
Japanese)<br />
38. (1914): On Anguillula stercoralis. Tokyo Iji Shinshi, (1870), 1082- 1092,<br />
(1872), 1196- 1198, (1873), 1239- 1247. (in Japanese)<br />
39. JONES, C. A. (1950): Clinical studies in human strongyloidiasis 1. Semeiology. Gastroenterology,<br />
16, 743- 756.<br />
40. KAGOSHIMA MEDICAL ASSOCIATION (1954): Symposium on the endemic diseases in the<br />
south Kyushu. Kagoshima Igaku Zasshi, 27 (5, 6), 116- 120. (in Japanese)<br />
41. KATO, S. (1921): Demonstration of Stl'ongyloides ste1'Coralis. Nippon Nailw Gakkai<br />
Zasshi, 9 (8). (in Japanese)<br />
42 . KATO, T. (1955) : The epidemiology of helminthiasis in Aichi Prefecture (Report<br />
1). Kiseichugaku Zasshi, 4 (1), 44- 49. (in Japanese with English summary)<br />
43. KATSUKI, s. (1951): Strongyloidiasis. Igaku, 11 (3), 184. (in Japanese)<br />
44. KAWAI, T. (1935): On the resistance of infective (filaria from) larvae of Strongyloides<br />
stercoralis against chemicals. Taiwan Igakkai Zasshi, 34 (12), 2051- 2062. (in Japanese)<br />
45. KAWAJI, K., H. KITAMURA, T. HASHIGUCHI, R . HAMADA & M. OYAMA (1956): An<br />
autopsy case of strongyloidiasis. Acta Pathologica Japonica, 6 (supp!.), 589- 592.<br />
46. KAWAMOTO, T. (1961): Studies on Strongyloides and strongyloidiasis (S-5). Susceptibilities<br />
to infective larvae of Strongyloides mtti SANDGROUND 1925 and S. stercoralis<br />
(BA VA Y, 1876) STILES et HASSALL, 1902. Kagoshima Daigaku Igaku Zasshi, 12 (6), 3169-<br />
3183. (in Japanese with English summary)<br />
47. KAWASAKI, H. (1924): An autopsy of strongyloidiasis stercomlis with assumptive cause<br />
of ulcer in colon. Nagasa/li Igakkai Zasshi, 2 (4), 453-470. (in Japanese)<br />
48. Kl]IMA, T. (1955): A case of strongyloidiasis. Kagoshima Igaku Zasshi, 28 (1, 2), 43.<br />
(in Japanese)<br />
49. KIMATA, N. (1903): Curious vomit, Anguillula intestinalis, found in a patient. Chuo<br />
Igakkai Zasshi, 54 (1). (in Japanese)<br />
50. KISHIDA, T. & M. HONMA (1952): A case of strongyloidiasis with gross intestinal<br />
bleeding. Tokyo Iji Shinshi, 69 (7), 424. (in Japanese)<br />
51. KOBAYASHI, M. & K. TAKIKAWA (1959): Studies on the secretion and excretion systems<br />
of Strongyloides mtti. Kiseichugaku Zasshi, 8 (3), 411. (in Japanese)<br />
52. KOGA, G. (1949): A severe case of strongyloidiasis. Kyushu Igakkaishi, 15. (in Japanese)<br />
53. (1955): Occurrence of Taenia solium in Tokunoshima Island. Kiseichugaku<br />
Zasshi, 4 (2), 144. (in Japanese)<br />
54. KOMIYA, Y. (1959): Parasitic infections and medicine. Yakkyoku, 10 (1), 109- 116. (in<br />
Japanese)<br />
55. KOSUGE, 1. (1924): Histologische Untersuchungen tiber das Eindringen von St1'Ongyloides<br />
stercoralis in die Haut von Versuchstieren. Arch. Schiff. Trop. Hyg., 28 .<br />
56. (1924): Wie weit wirken dem Eindringen von Strongyloides larven und anderen<br />
parasitischen Nematoden in das Gewebe spezifische Reize? Ibid., 28.<br />
57. (1924): Studies on the invasion of larvae of Strongyloides and other nematodes<br />
into the tissue. Jikken Igaku Zasshi, 8 (12), 1105-1111. (in Japanese)<br />
58. KREIS, H. A. (1932): Studies on the genus Strongyloides (Nematodes). Am. Jour. Hyg.,<br />
16, 450-491.<br />
59. KUROKAWA, H. (1950): Observation of intestinal parasites at Kanda Clinic and a consideration<br />
to the hook worm disease. Nippon Kiseichu Gakkai Kiji, 19, 41. (in Japanese)<br />
60. KUSUI, K. & S. USHYUKU (1934): Uber einen Fall von Anguillulose mit interessantem<br />
Rontgenbild des Dtinndarmes. Nagasaki Igakkai Zasshi, 12 (9), 1175- 1186. (in Japanese<br />
with German summary)<br />
61. LEICHTENSTERN, O. (1899): Zur Lebensgeschichte der Anguillula intestinalis. Cent.<br />
631
comparative studies on the effect of several kinds of anthelmintics. Nippon Kiseichtt<br />
Gakkai Kiji, 20, 64-65. (in Japanese)<br />
85. MORI, K. & S. KURODA (1948): A case of strongyloidiasis. Yo/wha ma Igaktt, 1 (1), 13-<br />
14. (in Japanese)<br />
86. MORISITA, T ., M. KOBAYASHI, Y. KUNII & K. T AKIKAWA (1959): Development of<br />
St1'ongyloides with relationship to Rhabditis. Nippon Iji Shinpo, (1817), 45-48. (in<br />
Japanese)<br />
87 . , Y. Y AMA KAWA & M. MORI (1959): Treatment of strongyloidiasis<br />
with dithiazanine. Gifu Ika Daigaku Kiyo, 7 (4), 1245- 1247. (in Japanese)<br />
88. NAGAo, M. (1918): On Anguillula viviPam found in a horse in Japan. Jikken Iga/zu<br />
Zasshi, 2 (2) . (in Japanese)<br />
89 . NAGASAWA, D. (1902): On Anguillula intestinalis. Tokyo Iji Shinshi, (1268), 1167-1175.<br />
(in Japanese)<br />
90. NAGOE, T . (1954 a) : An endemic disease on Tanegashima Island. Chiryo Yakuho, (514),<br />
11 . (in Japanese)<br />
9l. (1954 b): Strongyloidiasis and its treatment. Kagoshima Igaku Zasshi, 27<br />
(3, 4), 65- 68. (in Japanese with English summary)<br />
92. & T. YONEZAWA (1954) : Strongyloidiasis and its treatment on Tanegashima<br />
Island. Ibid., 27 (3, 4), 75. (in Japanese)<br />
93 . NAITO, H. (1928): A case of so-called Cochin-China diarrhea. Naigai Chi/'Yo, 3 (5) . (in<br />
Japanese)<br />
94 . NAKAJIMA, T. (1955): Malnutrition of young pigs due to S trongyloides mnsomi and<br />
curative effect of " Hinetol ". Jui Chikusan Shimpo, (157), 430- 433. (in Japanese)<br />
95 . NISHIGORI, M . (1925) : Life cycle and external development of Strongyloides stercomlis.<br />
(Ab) T aiwan Igakkai Zasshi, (248). (in Japanese)<br />
96. (1926): The development of St1'ongyloides stercomlis. Nippon BYQ1'i Gakkai<br />
Kaishi, 16 , 27l-274. (in Japnese)<br />
97 . (1927): The factors which influence the external development of Strongyloides<br />
ste1'Comlis and on autoinfection with this parasite.(Ab) Taiwan Igakkai Zasshi, (27l), Ibid.,<br />
(272). (in Japanese)<br />
98. (1928): Ibid., Ibid., (276), 291-311 ; (277), 397-43l. (in Japanese with English<br />
summary)<br />
99_ NISHIMURA, H. (1943): Helminths of alimentary tract of house rats in Fukuoka City.<br />
Fukuoka Ika Daigaku Zasshi, 36 (8), 726- 74l. (in Japanese)<br />
100. ODAWARA, T. (1954): Cases of strongyloidiasis. Kagoshima Igaku Zasshi, 27 (3, 4),<br />
64-65. (in Japanese)<br />
10l. OHIRA, T . (1913): On Strongyloides stercomlis especially on the pathogenicity. Tokyo<br />
Igakkai Zasshi, 27 (20), 1601-1646 . (in Japanese)<br />
102. (1914 a): False identification and its cause at the cultivation of hook worms<br />
and Strongyloides, in addition of studies on the free living nematodes. T okyo Iji Shinshi,<br />
(1887), 1929- 1936. (1888), 1977- 1983. (1889), 2031- 2038. (in Japanese)<br />
103. (1914 b): Criticism to the report of Dr. IWAYA on StTongyloides steTcomlis.<br />
Ibid. , (1874), 1305- 1307. (in Japanese)<br />
104. (1914 c): Criticism to the second report of Dr. IWA YA on St1-ongyloides steTcQ1-alis.<br />
Ibid., (1876), 1409- 1410. (in Japanese)<br />
105. (1914 d): A species of S tTongyloides in a monkey. Fukuoka Ika Daigalzu<br />
Zasshi, 8 (1), 90-96. (in Japanese)<br />
106. (1918): Problem whether human Strongyloides' is infective on the other<br />
animals, in addition of autoinfection. Tokyo Iji Shinshi, (2096), 2003-2009. (in Japanese)<br />
107. (1919): Studies on St1-ongyloides ste1-comlis. Tolzyo Igalzkai Zasshi, 33 (11),<br />
601- 633. (in Japanese)<br />
108. (1921) : Histological studies on human case of Strongyloides stercQ1-alis, on<br />
633
634<br />
experimental animal infections and on autoinfection of this nematode. Kanpo, (2681).<br />
(in Japanese)<br />
109. ONODERA, N. (1922): Human strongyloidiasis and diabetes. Fukuoka Ika Daigaku Zasshi,<br />
15 (3), 151- 155. (in Japanese)<br />
110. OSADA, M. (1952): Strongyloides stercoralis infections in three families in Tochigi Prefecture.<br />
Igaku to Seibutsugaku, 22 (4), 146- 149. (in Japanese)<br />
111. OSHIO, Y. (1956): Studies on the larval migration of Strongyloides ransomi at percutaneous<br />
infection. Nogyo Gijutsu Kenkyujyo Hokoku G., (12), 181-186. (in Japanese with<br />
English summary)<br />
112. & 1. FURUTA (1954): Studies on the infection of Sf1'ongyloides l"ansomi.<br />
Nippon juishikai Zasshi, 7, 259-261. (in Japanese)<br />
113. (1955 a): Studies on hyaluronidase in parasitic nematodes. Nogyo<br />
Gijutsu Kenkyujyo Hokoku G., 11, 47- 56. (in Japanese with English summary)<br />
114. (1955 b): Histological studies on the hide at the percutaneous<br />
infection of Strongyloides ransomi. Ibid., 11, 57- 66. (in Japanese with English summary)<br />
115. & A. TAKAHASHI (1958): Treatment and prevention of Strongyloides ransomi.<br />
Ibid., 14, 137- 143. (in Japanese with English summary)<br />
116. ROMAN, E. (1956): Specificite parasitaire de Strongyloides ratti du surmulot. Effets<br />
de la cortisone sur l'infestation d'autres rongeure par ce Nematode. Ann. de Parasit.,<br />
31 (5, 6), 552- 571.<br />
117. SAITO, S., N. YONEDA, M. MIURA & 1. OMURA (1959): On strongyloidiasis. Chil'YO, 41<br />
(5), 627- 632. (in Japanese)<br />
118. SANDGROUND, J. H. (1925): Speciation and specificity in the nematoda genus Strongyloides.<br />
jour. Parasit., 12 (2), 59-80.<br />
119. (1926) : Some biological studies of the lifecycle in the genus Strongyloides .<br />
Arch. Schif. Trop. Hyg., 30 (9), 528-533.<br />
120. SASA, M., S. HAYASHI, H. TANAKA, K. SATO, A. MIURA, M. WAKASUGI, R. SHIRASAKA,<br />
A. TAKATA, K. TOKURIKI, E. NAKAMURA & M. NAGANO (1957): Comparative studies<br />
on parasitic infections among coal miners in Kyushu and Hokkaido. Koshu Eisei, 21<br />
(11), 1- 9. (in Japanese)<br />
121. & R. SHIRASAKA (1958): Application of test· tube<br />
cultivation method on the survey of hookworms and related human nematode infection.<br />
japan. jour. Exp. Med., 28 (3), 129- 137.<br />
122. , H. TANAKA, Y. ABE, A. SUGIURA, H. UCHIYAMA, K. IZUMI & 1. TAKIKIKU<br />
(1958): Epidemiological studies on the human parasites at Amami-Oshima Island (1)<br />
Distributions of the main intestinal helminthic infections detected by direct smear,<br />
floatation and test-tube cultivation methods of fecal specimens. Kiseichugaku Zasshi, 7<br />
(4), 357- 362. (in Japanese with English summary)<br />
123. , S. HAYASHI, H. TANAKA, A. SUGIURA, Y. ABE, H. UCHIYAMA. K. IZUMI &<br />
1. TAKIKIKU (1958): Ibid. (2) Familial distributions of the parasites and correlations<br />
between infections of different parasites. Ibid., 7 (5), 449-453. (in Japanese with English<br />
summary)<br />
124. , K. TERUYA, K. IKEMIYA, S. KUNIYOSHI, S. SHIROMA & S. KIN]O (1958):<br />
On the parasitic infections at farming villages on Okinawa. Nippon Ishikai Zasshi, 39<br />
(9), 601-604. (in Japanese)<br />
125. SATO, H. (1956): Strongyloidiasis. Nippon Iji Shinpo, (1673), 111. (in Japanese)<br />
126. , H. FUKUSHIMA, E. IBUSUKI, S. TSUKASA & T. NONAKA (1958): On parasitic<br />
helminths, especially on hookworms and Strongyloides stercoralis in Amami Oshima.<br />
Kagoshima Daigaku Igaku Zasshi, 10 (4), 1140- 1147. (in Japanese with English summary)<br />
127. , H. TOYAMA, T. NONAKA, H. TERUYA, M . KUNI YOSHI & M.<br />
SHIROMA (1958): A study on parasitic helminth and filariasis bancrofti in Okinawa.<br />
Ibid., 10 (4), 1148- 1160. (in Japanese)
636<br />
mental stage of Strongyloides ratti SANDGROUND and statistical observations of the adult<br />
worms on the parasitizing parts in the specific host. Kagoshima Daigallu Igalltt Zasshi,<br />
12 (4), 1632- 1647. (in Japanese with English summary)<br />
149. TAKAHASHI , M. (1942): A case of strongyloidiasis stercoralis with ascites. j icchi IIw<br />
to Rinshyo , 19 (5), 402- 406. (in Japanese)<br />
150. TAKEDA, S. & S. T. RI (1924 a): A case of strongyloidiasis stercora lis. Chosen Igaldwi<br />
Zasshi, 47 . (in Japanese)<br />
151. (1924 b): A case of strongyloidiasis stercoralis. Ibid., 50, 352-<br />
355. (in Japanese)<br />
152. TAKEGAWA, T., H. SUGANUMA & M. EN DO (1958): Studies on parasites in Joban area<br />
especially among coal miners. Yollohama Igallu, 9 (3), 301-306. (in Japanese)<br />
153. TAKEUCHI , H. (1905): Experimental studies on Anguillula intestinalis as a causative<br />
agent of chronic idiopathic diarrhea. Taiwan Igallllai Zasshi, 3D, 260. (in Japanese)<br />
154. TANABE, K. (1938 a): External development of larvae of St1'ongyloides ratti and inter·<br />
nal development in norvegic and albino rats. (Ab) Nippon Kiseichu Galllwi Kiji, 10, 37.<br />
(in Japanese)<br />
155. (1938 b): Development of the larvae of Strongyloides ratti in the proper host.<br />
Keio Igallu, 18 (6), 785- 794. (in Japanese with English summary)<br />
156. (1938 c): Development of St1'ongyloides ratti in the albino rats. Ibid., 18 (7),<br />
867-877. (in Japanese with English summary)<br />
157. (1938 d): On influence of environmental conditions upon the development of<br />
Strongyloides ratti. Ibid., 18 (9), 987-999. (in Japanese with English summary)<br />
158. (1938 e): Supplemental studies on the determination of both types of external<br />
development of Strongyloides 1·atti. Ibid., 18 (10), 1139-1143. (in Japanese)<br />
159. (1939): On eosinophilia in the intestinal wall of the rat infected with<br />
Strongyloides 1'atti. Ibid., 19 (2), 2l3-229. (in Japanese with English summary)<br />
160. & H. TAKEISHI (1936): A survey of helminths in the digestive system of<br />
the rat. Ibid., 16 (11), 1767- 1785. (in Japanese with English summary)<br />
161. TANAKA, H. (1957 a): Studies on St1"ongyloides stercoralis. Kiseichugallu Zasshi, 6 (3,<br />
4), 293. (in Japanese)<br />
162. (1957 b): Studies on strongyloidiasis. 1) Epidemiological observations in<br />
Amami·Oshima Island. juntendo Igallu Zasshi, 3 (I), 22-30. (in Japanese with English<br />
summary)<br />
163. (1957 c): Ibid. 2) Cultivation methods and morphological observations of<br />
Strongyloides in the free· living phase. Ibid., 3 (2), 91- 100. (in Japanese with English<br />
summary)<br />
164. (1957 d): Ibid. 3) Clinical studies of experimental and natural infections.<br />
Ibid. , 3 (3), 155- 162. (in Japanese with English summary)<br />
165. (1958): Experimental and epidemiological studies on strongyloidiasis of<br />
Amami·Oshima Island. japan jour. Exp. Med. 28 (3), 159- 182.<br />
166. (1964): Studies on the treatment of human strongyloidiasis with pyrvinium<br />
pamoate suspension. Chi/'Yo Yalluho, (631). (in Japanese)<br />
167. & R . AMANO (1959): The course of the evacuated numbers of eggs of<br />
Strongyloides ratti. (Ab) Kiseichugallu Zasshi, 8 (3), 412. (in Japanese)<br />
168. & (1960): Studies on Strongyloides 1'atti with a special reference<br />
to the screening test for Strongyloides anthelmintics. Bull. Tollyo Med. Dent. Univ.,<br />
7 (2), 193-230.<br />
169. , K. S UGIYAMA & Y. SHIROMA (1959): Detection of St1"Ongyioides<br />
ratti from house rats by fecal examination. Ochanomizu IgallU Zasshi, 7 (I), 195-200.<br />
(in Japanese with English summary)<br />
170. , N. KUMADA, K. FUKUMINE, H. KAWAMITSU, H. TOKUMINE & C. IJYU (1959):<br />
Examination of nematode infections on Miyako Island, Ryukyu. Koshyu Eisei, 23 (8),
523- 527. (in Japanese)<br />
171 . , Y. SHIROMA & R. AMANO (1960): Application of dithiazanine iodide to the<br />
treatment of human strongyloidiasis. Kiseichugaku Zasshi, 9 (4), 415. (in Japanese)<br />
172. , N. KUMADA, K. FUKUMINE & H. KAWAMITSU (1960) : An effica·<br />
cious application of gential violet to the treatment of strongyloidiasis. Bull. TollYo Med.<br />
Dent. Univ., 7 (1), 137- 150.<br />
173. , H. TOKURIKI , R. SHIRASAKA & S. HAYASHI (1958): On Strongyloides<br />
ste1'coralis with special refference to its detection. Naika no Ryoiki, 6 (5), 335- 340. (in<br />
Japanese)<br />
174. TANI, M. & H. UZAWA (1954): An autopsy case of heavy infection of Strongyloides<br />
accompanied with liver cirrhosis. Saisei, (315), 46. (in Japanese)<br />
175. TASHIRO, 1. (1912 a): Studies on Strongyloides stercoralis in Japan. Saikingaku Zasshi,<br />
(198), 273-287. (in Japanese)<br />
176. (1912 b): Studies on StTongyloides stercoralis in Japan with special refference<br />
to its infection in dogs. Ibid., (204), 805-811. (in Japanese)<br />
177. TERASHI, K. (1953): Strongyloidiasis. Kagoshima Igalm Zasshi, 26 (11. 12), 282- 283 . (in<br />
Japanese)<br />
178. & Y. NAKAM URA (1954): Strongyloidiasis in the Isa Gun area. Ibid., 27 (7. 8),<br />
179. (in Japanese)<br />
179. TOMITA , S. (1937): External development of Genus Sf1'ongyloides, GRASSI. Taiwan<br />
Igakkai Zasshi, 36 (12), 2825- 2826 . (in Japanese)<br />
180. (1938): On the resistance of the filariform larvae of St"ongyloides papillosus<br />
to various agents. Ibid., 37 (7), 1104- 1111. (in Japanese)<br />
181. (1939): On the species of Strongyloides harbouring in Formosan pig and<br />
monkey. Ibid., 38 (11), 1613- 1624. (in Japanese)<br />
182. (1940 a): On the difference of infectivity of S. papillosus and S. jiilleborni<br />
upon dogs and monkeys. Ib id., 39 (10), 1649- 1650. (in Japanese)<br />
183. (1940 b): Experiment on the susceptibility of men to infection by Strongy.<br />
loides jiilleborni and by Strongyloides papillosus. Ibid., 39 (11), 1884- 1885. (in Japanese)<br />
184. (1941 a): Cutaneous reaction at the innoculated area, clinical and hematolo·<br />
gical courses at human experimental infection of Strongyloides papillosus and St1'ongy,<br />
loides jiilleb01·ni. Ib id., 40 (1), 149- 150. (in Japanese)<br />
185 . (1941 b): Ibid. Ibid., 40 (3), 427-443. (in Japanese)<br />
186. (1941 c): On the host specificity of Strongyloides jiilleb01'ni and Strongyloides<br />
papillosus. Ibid., 40 (11), 2147- 2157. (in Japanese)<br />
187. TSUKASA, S. & T . HASHIGUCHI (1959): Ecological and histochemical studies on St,·ongy·<br />
loides stenoralis. (Ab) Kiseichugaku Zasshi, 8 (3), 410. (i n Japanese)<br />
188. TSUNODA, S. (1934): On the parasitic disease of Strongyloides ste1'coralis. Tokyo Iji<br />
Shinshi, (2894), 2059-2063. (in Japanese)<br />
189. UCHIZONO, Y. (1954) : Strongyloidiasis. Kagoshima Igaku Zasshi, 27 (3, 4), 75. (in<br />
Japanese)<br />
190. UENO, M. (1948): A case of StTongyloides steno1'alis. Kagoshima Igaku Zasshi, 21 (7).<br />
(in Japanese)<br />
191. UMEKI, O. (1951): A case of strongyloidiasis with appearance of larvae in pleural and<br />
peritoneal effusion. (Ab) Nippon Naika Gakkai Zasshi, 40 (7), 392. (in Japanese)<br />
192. WATANABE, S. (1956): Internal parasitic diseases of pigs and their control. Chikusan<br />
no Kenkyu, 10 (1), 217- 220. (in Japanese)<br />
193. YAMADA, M. (1907): A case of Rhabdonema strongyloides in Japan. Iji Shinbun, 73 1.<br />
(in Japanese)<br />
194. YAMAGUCHI, T . (1958): Histochemical studies on parasitic helminths. 3) Histochemical<br />
studies on larvae of Ancylostoma duodenale and Strongyloides ratti. Kiseichugaku<br />
Zasshi, 7 (1), 29-36. (in Japanese with English summary)<br />
637
638<br />
195. YAMAGUTI, S. (1925) : Ueber die durch Larven von Ascaris lumbl'icoides und Strongyloides<br />
stercoralis an Gehirn und Nieren verursachten Vedinderungen. Arch. Sch-i/. Trop.<br />
Hyg., 29 (10), 589-604.<br />
196. YOKOGAWA, S. (1913): On the pathogenicity of Strongyloides stercoralis. Taiwan<br />
Igakkai Zasshi, (127) . (in Japanese)<br />
197. (1914): The second report on the pathogenicity of Strongyloides stercoralis.<br />
Nippon Shokakibyo Gakkai Zasshi, 13 (1). (in Japanese)<br />
198. (1929): The autoinfection and the principle of the treatment of St1'Ongyloides<br />
sterc01'alis. Chil'Yo oyobi Shoho, 10 (107), 123-126. (in Japanese)<br />
199. & T. OISO (1925 a): Studies on the life cycle of hookworms and Strongyloides<br />
stercomlis. Pts. 1- 3. Tokyo Iii Shinshi, (2418), 971- 977; (2425), 1336- 1340; (2439), 2022-<br />
2028. (in Japanese)<br />
200. & (1926 a): Studies on the life cycle of hookworms and Stl'ongyloides<br />
stel'coralis. Ibid., (2456), 327-337. (in Japanese)<br />
201. & (1925 b, 1926 b): Ibid. Taiwan Igakkai Zasshi, (241), (246),<br />
(248), (250). (in Japanese)<br />
202. YOSHIDA, H., R. TAKADA & S. ITO (1931): Clinical and pathological observations in a<br />
case of Strongyloides ste1'Coralis. Gunidan Zasshi, (213), 464. (in Japanese)<br />
203. (1932): Ibid. Kaigun Gunikai Kaishi, 21 (2), 132.<br />
(in Japanese)<br />
204. YOSHIDA, J. (1940): A case of Stl'ongyloides ste1'Comlis. Kumamoto Igakkai Zasshi, 16<br />
(1), 174. (in Japanese)<br />
205. YOSHIDA, S. (1918): On the course of internal migration in the peroral larval infections<br />
of hookworms and Stl'ongyloides stercoralis. Tokyo Iii Shinshi, (2088), 1639-1644. (in<br />
Japanese)<br />
206. YOSHINAGA, K. (1950): A case of Strongyloides ste1'Comlis with perforated peritonitis.<br />
Rinshyo to Kenkyu, 27 (9), 631- 633. (in Japanese)<br />
207. (1950): Ibid. Nippon Byori Gakkai Zasshi, 39, Editio generalis, 265-266. (in<br />
Japanese)<br />
208. YOSHINO, K. (1932): Clinical observations of 25 cases of strongyloidiasis in Yaeyama<br />
Islands, Okinawa, Japan. Taiwan Igakkai Zasshi, 31 (9), 1067- 1080; 31 (10), 1124- 1138.<br />
(in Japanese with English summary)<br />
209. (1939) : An application of gentian violet to the treatment of Strongyloides<br />
stel'coralis. Tokyo Iii Shinshi, (3124), 566-569. (in Japanese)