특집_공윤

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1 Focused Issue of This Month Tissue Invading Helminthic Diseases Yoon Kong, MD Department of Molecular Parasitology, Sungkyunkwan University School of Medicine ykong@med.skku.ac.kr J Korean Med Assoc 2007; 50(11): Abstract Modernized urban life style has changed patterns of parasitic infections in Korea. Parasitic diseases caused by soiltransmitted helminths and waterborne protozoans has significantly decreased, while imported parasitic diseases, zoonosis, and opportunistic infections are being increasingly recognized. Tissueinvading helminthiases also invoked formidable health problems, which had been neglected due to the difficult clinical diagnosis and slow progression. However, the diseases are associated with chronic morbidity and severe mortality. A variety of helminths invade the human tissue. With an exception of few entities (i.e., schistosomiasis, clonorchiasis, and paragonimiasis), most of tissueinvading helminths are associated with larvae/juveniles but not with adults. Larval infections might be more serious, since the larvae may migrate throughout the whole body, after which they lodge in critical foci in the brain, eye, liver, or elsewhere or may grow into large masses exerting spaceoccupying effects (i.e., cysticercosis, sparganosis, and hydatidosis). When the parasites invade the tissue, IgE levels are modulated by several effector molecules including interleukin (IL)4, IL6, interferon and other cytokines secreted by different Thcell subsets. Immediatetype hypersensitivity is related to huge production of Th2type cytokines, mast cells, eosinophils, and IgE. These immune interactions elicit cellular responses, culminating in immunophysiological changes, which protect the host by surrounding the invasive parasite with granuloma. However, hyperactivation of the immune system may also be harmful to the host, resulting in immunemediated diseases. This article briefly reviews the biology, clinical manifestations, diagnosis, and principle of the treatment of the tissueinvading helminthic infections, which are important in Korea. Keywords : Tissue invading helminths; Nematode; Trematode; Cestode; Larva/ Juvenile infection 967

2 Kong Y 968

3 Tissue Invading Helminths Table 1. Major parasitic diseases affecting human tissues Parasites/Diseases Predilection sites Route of infection Source/Intermediate host / Vector Chief complaint Diagnosis (otherthan image) Treatment of choice Nematodes Toxocara canis / T. catti (Toxocariasis / visceral larva migrans)* Trichinella spiralis (Trichinellosis)* Brugia malayi (Lymphatic filariasis)* Gnathostoma spinigerum (Gnathostomiasis) Anisakis simplex (Anisakiasis/ herring disease)* Capillaria hepatica (Hepatic capillariasis)* Trematodes Schistosoma manosoni (Schistosomiasis) Schistosoma japonicum (Schistosomiasis) Schistosoma haematobium (Schistosomiasis) Clonorchis sinensis (Clonorchiasis)* Paragonimus westermani (Paragonimiasis)* Cestodes Taenia solium metacestodes (Cysticercosis)* Echinococcus granulosus (Cystic echinococcosis) Echinococcus multilocularis (Alveloar echinococcosis) Spirometra species (Sparganosis) Protozoa Leishmania donovani (Visceral leishmaniasis) Leishmania tropica (Mucosal leishmaniasis) Entamoeba histolytica (Amoebiasis)* Toxoplasma gondii (Toxoplasmosis)* Pneumocystis carinii (Interstitial pneumonia)* Lung, liver, eye, brain Muscle Lymphatics Subcutane - ous tissue Stomach, small intestine Liver Inferior mesenteric vein Superior mesenteric vein Perivesical plexus Common bile duct Lung, ectopic migration Brain, eye, subcutaneous tissue Liver, lung, brain, bone Liver Brain, subcutaneous tissue Endothelial cells, macrohpage Mucosal macrophage Liver, colon, brain Nucleated cells Lung Skin Skin Skin Skin, skin Skin Skin Respiratory Egg Encysted larva (pork) Mosquitos 2nd / 3rd-stage larva (fish/pork) 2ndstage larva (fish) Egg Cercaria (swimming) Cercaria (swimming) Cercaria (swimming) Metacercaria (freshwater fish) Metacercaria (freshwater crustacean), boar meat Egg Egg Egg Procercoid (water), plerocercoid (frog / snake) Sandfly Sandfly Cyst / polluted water Oocyst, vertical infection Respiratory Eosinophilia, pneumonitis Eosinophilia, myalgia Fever, lymphangitis, elephantiasis Eosinophilia, Subcutaneous nodule Abdominal pain Hepatomegaly, eosinophila Chronic dysentery Hepatic dysfunction Urinary disturbance Easy fatigability Hemoptysis, cough Seizure, subcutaneous nodule Space occupying lesion Similar to hepatic cancer Subcutaneous nodule, CNS symptoms Fever, hepatosplenomegaly Mucosal ulcer Hepatomegaly, diarrhea, fever Lymphadenitis, CNS symptoms Pneumonia Biopsy, EIA Biopsy, EIA Blood smear, EIA Biopsy, EIA Biopsy, EIA Liver biopsy Egg (stool), EIA, Retal / hepatic biopsy Egg (stool), EIA, hepatic biopsy Egg (urine), EIA, cytoscopy Egg (stool), EIA Egg (stool/sputum), EIA Biopsy, EIA Biopsy, EIA Biopsy, EIA Biopsy, EIA Hepatic biopsy Wedge biopsy Stool examination, aspiration biopsy, EIA Biopsy, EIA BAL, lung biopsy Thiabendazole Thiabendazole Diethylcarbamazine, ivermectin Removal Removal Thiabendazole Praziquantel Praziquantel Praziquantel Praziquantel Praziquantel Praziquantel, surgery Albendazole, surgery Albendazole, surgery Removal surgery Amphotericin B deoxycholate Meglumine Metronidazole Pyrimethamine sulfonamide Trimethoprim sulfamethoxazole * Endogenous cases have been reported in Korea Imported cases have been reported in Korea ELISA and immunoblot 969

Kong Y Figure 1. A 52yearold woman complained of RUQ discomfort and cough. CBC revealed an eosinophilia of 76%. On ultrasonographic examination of the liver, approximately 0.

4 Kong Y Figure 1. A 52yearold woman complained of RUQ discomfort and cough. CBC revealed an eosinophilia of 76%. On ultrasonographic examination of the liver, approximately 0.6 cm sized multiple hypodense nodules were noticed. She showed high serum IgG antibody levels against excretorysecretory antigen of L2 stage Toxocara larvae. [Courtesy of Dr. SP Lee (Gacheon University)] 970

WM Sohn (Gyeongsang National University)] A) Encysted larvae of T.

5 Tissue Invading Helminths A B Figure 2. Histopathological finding of Trichinella spiralis muscle larvae. [Courtesy of Dr. WM Sohn (Gyeongsang National University)] A) Encysted larvae of T. spiralis in the diaphragm of experimental mouse. B) Pathological examination of the biopsied muscle of a patient infected with T. spiralis showing encysted larvae surrounded by heavily infiltrated inflammatory cells. 971

part. Lymph spaces are obliterated by lymphedema.

6 Kong Y A Figure 3. Filarial elephantiasis of the upper and lower extremities. In the final stage of the lymphatic filariasis, tortuous, dilated lymphatic channels resulted in the obstruction of the proximal part. Lymph spaces are obliterated by lymphedema. Fibroblasts might migrate into edematous spaces and caused a thickening of the subcutaneous connective tissue. [Courtesy of Dr. TS Kim (Korea Natonal Institute of Health)] A) Elephantiasis involving the lower extremities B) Elephantiasis of the upper extremities B 972

A long whitish larva is penetrating the gastric mucosal fold

7 Tissue Invading Helminths A B Figure 4. Endoscopic finding of gastric anisakiasis. A long whitish larva is penetrating the gastric mucosal fold in the greater curvature of the mid body. [Courtesy of Dr. WM Sohn (Gyeongsang National University)] 973

bile ducts. Note the slightly hyperechoic bands along dilated ducts, representing increased periductal echogenicity.

8 Kong Y A B Figure 5. Sonograms of patients with Clonorchis sinensis. [Courtesy of Dr. DI Choi (Sungkyunkwan University) and Dr. ST Hong (Seoul National Univeristy)] A) Transverse scan of the left hepatic lobe shows moderate dilatation of the intrahepatic bile ducts. Note the slightly hyperechoic bands along dilated ducts, representing increased periductal echogenicity. B) Oblique scan of the gallbladder shows several floating echogenic foci (arrows), which indicate worms or desquamated materials. 974

9 Tissue Invading Helminths Figure 6. Abdominal CT of a hepatic fascioliasis patient. Huge low density mass suggested a live abscess. Multiple focal tractlike lesions were also observed. The patient revealed high levels of specific antifasciola antibodies in her serum by ELISA. 975

A) Simple chest radiograph shows dense masslike

B) Consolidations with multiple cysts on chest HRCT.

cerebral case reveals caseous materials filled the

10 Kong Y A B C D E Figure 7. Pulmonary and cerebral paragonimiasis. A) Simple chest radiograph shows dense masslike consolidation, nodules and thinwalled cysts. B) Consolidations with multiple cysts on chest HRCT. C) Lateral view of simple skull revealed a.soup bubblelike calcifications. D) Calcified granuloma surgically removed from a cerebral case reveals caseous materials filled the granuloma. Smearing of the granuloma wall and content, necrotic parasite eggs are detected. E) High density conglomerated lesions of calcified granulomas on CT scan. 976

11 Tissue Invading Helminths Figure 8. Declining patterns of specific antibody levels in sera of paragonimiasis after treatment against different antigens of P. westermani by ELISA. In most cases of tissue invading helminthic infections, similar serological profiles after the successful treatment could be observed. 977

12 Kong Y Figure 9. Brain image of neurosparganosis. An extensive area of white matter angioneurotic edema in the left parietal lobe associated with an irregular enhancing mass is observed by brain MRI. 978

13 Tissue Invading Helminths Figure 10. Subcutaneous and cerebral cysticercosis. A) Simple abdomen shows multiple slender, ovoid calcifications. B) Multiple lowdensity lesions are noticed by brain MRI. A B 979

14 Kong Y 980

15 Tissue Invading Helminths 11. Ministry of Health and WelfareKorea Association of Health Promotion. Prevalence of intestinal parasitic diseases in KoreaThe seventh Report. Korea Association of Health Promotion. Seoul, Korea Kwon NH, Oh MJ, Lee SP, Lee BJ, Choi DC. The prevalence and diagnostic value of toxocariasis in unknown eosinophilia. Ann Hematol 2006; 85: Sohn WM, Kim HM, Chung DI, Yee ST. The first human case of Trichinella spiralis infection in Korea. Korean J Parasitol 2000; 38: Chai JY, Han ET, Shin EH, Park JH, Chu JP, Hirota M, NakamuraUchiyama F, Nawa Y. An outbreak of gnathostomiasis among Korean emigrants in Myanmar. Am J Trop Med Hyg 2003; 69: Choe G, Lee HS, Seo JK, Chai JY, Lee SH, Eom KS, Chi JG. Hepatic capillariasis: First case in the Republic of Korea. Am J Trop Med Hyg 1993; 48: Sutherst RW. Global change and human vulnerability to vectorborne diseases. Clin Microbiol Rev 2004; 17: Mostafa MH, Sheweita SA, Relationship between schistosomiasis and bladder cancer. Clin Microbiol Rev 1999; 12: Ross AG, Vickers D, Olds GR, Shah SM, McManus DP. Katayama syndrome. Lancet Infect Dis 2007; 7: Goncalves MM, Barreto MG, Peralta RH, Gargioni C, Goncalves T, Igreja RP, Soares MS, Peralta JM. Immunoassays as an auxiliary tool for the serodiagnosis of Schistosoma mansoni infection in individuals with low intensity of egg elimination. Acta Trop 2006; 100: Koukounari A, Sacko M, Keita AD, Gabrielli AF, Landoure A, Dembele R, Clements AC, Whawell S, Donnelly CA, Fenwick A, Traore M, Webster JP. Assessment of ultrasound morbidity indicators of schistosomiasis in the context of large scale programs illustrated with experiences from Malian children. Am J Trop Med Hyg 2006; 75: Choi BI, Han JK, Hong ST, Lee KH. Clonorchiasis and cholangiocarcinoma: Etiologic relationship and imaging diagnosis. Clin Microbiol Rev 2004; 17: Cho SY, Bae JH, Seo BS. Some aspects of human sparganosis in Korea. Korean J Parasitol 1975; 13:

16 Kong Y 13. Chang KH, Kim WS, Cho SY, Han MC, Kim CW. Comparative evaluation of brain CT and ELISA in the diagnosis of neurocysticercosis. Am J Neuroradiol 1988; 9: Chang KH, Han MH. MRI of CNS parasitic diseases. J Magn Reson Imaging 1998; 8: Cho SY, Kim SI, Kang SY, Choi DY, Suk JS, Choi KS, Ha YS, Chung CS, Myung HJ. Evaluation of enzymelinked immunosorbent assay in serological diagnosis of human neurocysticercosis using paired samples of serum and cerebrospinal fluid. Korean J Parasitol 1986; 24: Chung JY, Bahk YY, Huh S, Kang SY, Kong Y, Cho SY. A recombinant 10kDa protein of Taenia solium metacestodes specific to active neurocysticercosis. J Infect Dis 1999; 180:

17 Tissue Invading Helminths Peer Reviewer Commentary 983

Special Issue Food borne Parasitic Diseases Jong Yil Chai, M.D. Department of Parasitology and Tropical Medicine Seoul National University College of

Special Issue Food borne Parasitic Diseases Jong Yil Chai, M.D. Department of Parasitology and Tropical Medicine Seoul National University College of Medicine E mail : cjy@snu.ac.kr Abstract This article