선천성 톡소플라스마증(Toxoplasmosis)의 실험적 연구

Abstract

[한글]

Toxoplasma gondii의 생활사는 최근에 이르러서야 규명되었는데 Frenkel 등(1970)과 Hutchison등(1971)에 의해 고양이가 종숙주임이 밝혀져 전파경로에 관하여 점점 새로운 사실이 알려지고 있으며 고양이의 분변으로 오염된 식품이나 본 원충에 감염된 동물의 생식

에 의해 경구 감염된다고 인정되고 있으며 (Durfee and Chien, 1971: Magaldi et al., 1969), Cowen 및 Wolf(1950)는 임신된 마우스에 본 원충을 질(膣)내로 감염시켰을 때 태아에서 선천감염이 이루어진다고 하였다.

T. gondii의 자연계에서의 전파 양상에 있어 규명되지 못한 부분이 아직도 많으며, 사람의 선천성 톡소플라스마증에 관하여 우리나라에서 Choi등(1980)과 Chung등(1980) 임상예가 보고되고 있지만, 특히 감염된 모체(母體)로부터 태반을 통해 태아로 감염되는 경로나 과정은 이해되지 않는 점들이 적지 않다.

임신된 마우스에 T. gendii RH주를 임신기간별로 하지 대퇴부 피하로 주입하여 감염시켜서 마우스모체의 간장과 비장에서 원충 충체를 검출함으로 감염된 것을 확인하고, 자궁내 마우스태아, 태반 및 신생(新生)마우스의 장기조직에서 원충을 검출함과 아울러 그 분

포상태를 관찰하고 이들 장기 조직의 병리학적 변화를 관찰함으로 실험동물 마우스를 사용하여 선천성 톡소플라스마증의 가능성을 알아보고저 하였다.

마우스의 하지대퇴부 피하조직에 T. gondii RH주를 감염시켰을 때 감염시키는 충체 수에 관계없이 그 생존기간은 10∼11일이었고, 마우스모체 간장과 비장에서 원충이 무수히 검출되었다.

임신 1∼2일째 감염시키고 8∼9일 경과후 관찰된 태반과 마우스 태아 체내조직에서 원충이 검출되었다. 임신기간 3∼9일에 감염시켰을 때 태반에서 T.gondii충체가 무수히 검출되었고 마우스의 자궁내 태아 일부에서 원충 충체가 존재함을 알 수 있었다.

임신기간 11∼16일후 감염시켰을 때 자궁내 태아의 간장, 신생마우스의 간장과 비장 조직에서는 충체를 관찰할 수 없었다.

T.gondii에 감염된 간장실질조직을 보던 괴사가 심하여 간엽구조가 파괴되고 미세농양이 불규칙하게 산재되었으며, 혈관주위에 염증세포의 심한 침윤이 관찰되었다. 괴사부위와 혈관주위에 많은 원충 충체가 관찰되었다. 비장에서는 미만성 울혈과 부분적 괴사가

있고 white pulp의 위축이 동반되고 다수의 충체가 보였다. 태반에서는 융모간 혈관의 울혈, 혈관내 웅괴가 있었고, 영양막 세포의 변성이 관찰되고 미만성 염증세포의 침윤이 동반되었고 영양막 세포내에서 T.gondii충체가 관찰되었다. 임신 7일에 감염시킨 태아의 간으로 생각되는 조직에서 T.gondii충체를 볼 수 있었다.

이상의 실험성적으로 보아 T.gondii를 피하로 주입 감염시킨 마우스에 있어 선천성 톡소플라스마증이 발생할 수 있으며 특히 임신전반기에 감염되었을 때 그 가능성은 더욱 높음을 알 수 있었다.

Experimental Study on Congenital Toxoplasma gondii Infection in Mice

Suk-Kyou Cha

Department of Medical Science The Graduate School, Yonsei University

(Directed by prof. Keun-Tae, Lee, M.D. and Pref. Duk-Jin Yun, M.D.)

The new knowledge on transmission of Toxoplasma gondii was introduced recently.

Frenkel et al. (1770) and Hutchison et al. (1971) reported that the cat acts as a

final host. Toxoplasmosis in man probably occurs by oral ingestion of food

contaminated by cat feces or infected raw animal meat (Durfee and Chien, 1971;

Magaldi et al., 1969). Toxoplasmosis was transmitted to mice by the introduction of

T.gondii into the vagina and pregnant mice were more susceptible to infection than

non-pregnant mice (Cowen and Wolf, 1950a).

The mode of transmission in man has not been known, especially in the case of

congenitaltoxoplasmosis. Several clinical and subclinical toxoplasmosis cases were

detected by Choi et al. (1980) and Chung et al. (1980). It is generally accepted

that the T.gondii tachyzoites are the forms which cross the placenta to infect the

fetus during the acute stage of toxoplasmosisin a pregnant mother. However, many

unsolved facts still remain, especially about the process of transferance of

T.gondii from pregnant infected mice to the fetuses.

T.gondii invasion into the liver and spleen was confirmed in the pregnant mice

inoculated subcutaneously. The detection of T.gondii tachyzoites in the tissue was

carried out by the direct fluorescent antibody test using anti-T. gondii pig serum

fluorescein·labelled. The possibility of experimental congenital toxoplasmosis was

studied by observation of the pathology induced by parasites after detection of

T.gondii in the placenta, intrauterine fetus and offspring of mice infected during

pregnancy.

Pregnant female mice, ICR-JCL strain, weighing about 15gm were used in this

experiment. Mice were injected subcutaneously in the flexor surface of the thigh

with T.gondii, R-Hstraits, which was prepared from peritoneal exudate of infected

mice.

The Survival Period Of infected Mice was 10-11 days without regard to the number

of T.gondii, tachyzoites injected subcutaneously. Many tachyzoites were observed

in the liver and spleen of pregnant mice.

Tachyzoites in the fetus with placenta were detected when inoculated between the

1st and 2nd day of pregnancy. Many parasites were seen in the placental tissue when

inoculated between the 3rd and 9th day of pregnancy and were identified in the 10

fetal tissues of 70pregnant mice. No tachyzoites were observed in the fetal liver,

neonatal liver and spleen when inoculation of parasites was done between the 11th

and 16th day of pregnancy.

Severe liver cell degeneration, necrosis and inflammatory cells infiltration were

present together with the destruction and dissociation of hepatic lobules and

multiple abscesses. Numerous T.gondii, tachyzoites were found both in the

hepatocytes and in the sinusoids around the perivascular region and the necrotic

area. In the spleen, diffuse congestion, partial necrosis and atrophy of white pulp

were observed, and numerous organisms of T.gondii were also found in the sinusoids

of red pulp adjacent to the necrotic area. Degeneration of trophob1asts and marked

congestion of intervillous spaces were seen. The aggregated parasites in

trophoblasts and focal area of coagulation necrosis were noted and diffuse

inflammatory cells infiltration was seen. T.godii was demonstrated in the fetal

liver of the mice infected on the 7th day of pregnancy.

The above mentioned results suggest that congenital toxoplasmosis in mice may be

induced experimentally by infection with T.gondii during pregnancy through the

subcutaneous route. It is particulary possible when the mice are infected during

the first half of pregnancy

[영문]

The new knowledge on transmission of Toxoplasma gondii was introduced recently.

Frenkel et al. (1770) and Hutchison et al. (1971) reported that the cat acts as a final host. Toxoplasmosis in man probably occurs by oral ingestion of food contaminated by cat feces or infected raw animal meat (Durfee and Chien, 1971; Magaldi et al., 1969). Toxoplasmosis was transmitted to mice by the introduction of T.gondii into the vagina and pregnant mice were more susceptible to infection than non-pregnant mice (Cowen and Wolf, 1950a).

The mode of transmission in man has not been known, especially in the case of congenitaltoxoplasmosis. Several clinical and subclinical toxoplasmosis cases were detected by Choi et al. (1980) and Chung et al. (1980). It is generally accepted

that the T.gondii tachyzoites are the forms which cross the placenta to infect the fetus during the acute stage of toxoplasmosisin a pregnant mother. However, many unsolved facts still remain, especially about the process of transferance of

T.gondii from pregnant infected mice to the fetuses.

T.gondii invasion into the liver and spleen was confirmed in the pregnant mice inoculated subcutaneously. The detection of T.gondii tachyzoites in the tissue was carried out by the direct fluorescent antibody test using anti-T. gondii pig serum

fluorescein·labelled. The possibility of experimental congenital toxoplasmosis was studied by observation of the pathology induced by parasites after detection of T.gondii in the placenta, intrauterine fetus and offspring of mice infected during

pregnancy.

Pregnant female mice, ICR-JCL strain, weighing about 15gm were used in this experiment. Mice were injected subcutaneously in the flexor surface of the thigh with T.gondii, R-Hstraits, which was prepared from peritoneal exudate of infected mice.

The Survival Period Of infected Mice was 10-11 days without regard to the number of T.gondii, tachyzoites injected subcutaneously. Many tachyzoites were observed in the liver and spleen of pregnant mice.

Tachyzoites in the fetus with placenta were detected when inoculated between the 1st and 2nd day of pregnancy. Many parasites were seen in the placental tissue when inoculated between the 3rd and 9th day of pregnancy and were identified in the 10 fetal tissues of 70pregnant mice. No tachyzoites were observed in the fetal liver, neonatal liver and spleen when inoculation of parasites was done between the 11th and 16th day of pregnancy.

Severe liver cell degeneration, necrosis and inflammatory cells infiltration were present together with the destruction and dissociation of hepatic lobules and multiple abscesses. Numerous T.gondii, tachyzoites were found both in the hepatocytes and in the sinusoids around the perivascular region and the necrotic

area. In the spleen, diffuse congestion, partial necrosis and atrophy of white pulp were observed, and numerous organisms of T.gondii were also found in the sinusoids of red pulp adjacent to the necrotic area. Degeneration of trophob1asts and marked

congestion of intervillous spaces were seen. The aggregated parasites in trophoblasts and focal area of coagulation necrosis were noted and diffuse inflammatory cells infiltration was seen. T.godii was demonstrated in the fetal liver of the mice infected on the 7th day of pregnancy.

The above mentioned results suggest that congenital toxoplasmosis in mice may be induced experimentally by infection with T.gondii during pregnancy through the subcutaneous route. It is particulary possible when the mice are infected during

the first half of pregnancy