論文 - 丸山 治彦
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Evaluation of LIPS (luciferase immunoprecipitation system) for serodiagnosis of Toxoplasmosis. 査読あり
Aye, K.M., Nagayasu, E., Baba, M., Yoshida, A., Takashima, Y., Maruyama, H.
Journal of immunological methods 462 91 - 100 2018年11月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Immunological Methods
© 2018 Elsevier B.V. Development of reliable, quantitative technologies for serodiagnosis of Toxoplasma gondii infection remains desirable. The luciferase immunoprecipitation system (LIPS) is a relatively simple, highly sensitive, and rapid quantitative immunoassay. The major advantages of this assay over ELISA are a wider dynamic range, shorter overall assay time, and less sample volume. In this study, we aimed to use this method for the serodiagnosis of toxoplasmosis. Recombinant Toxoplasma antigens (dense granule antigens GRA6, GRA7, and GRA8 and bradyzoite antigen BAG1) fused with nanoluciferase (Nluc, a small luciferase enzyme) were expressed in Escherichia coli, purified, and tested in LIPS assays with sera from experimental mice infected with T. gondii and a WHO standard anti-Toxoplasma human immunoglobulin (TOXM). In the experimentally infected mice, LIPS assays detected antibodies against Nluc-GRA6, Nluc-GRA7, and Nluc-GRA8 as early as day 14, whereas antibodies against Nluc-BAG1 remained undetected until day 21 and then showed significant elevation on day 60. In TOXM sera, LIPS assays with each Nluc recombinant protein produced reliable standard curves with a coefficient of determination (R 2 ) of 0.980–0.989 for GRA6, 0.986–0.990 for GRA7, 0.998–0.999 for GRA8, and 0.942–0.987 for BAG1. The detection limits were estimated to be 3.9, 2, 1, and 1 IU/ml for rGRA6, rGRA7, rGRA8, and rBAG1, respectively. The LIPS assay for toxoplasmosis could detect antibodies against T. gondii in the mouse and human sera with a reasonably high sensitivity. We consider the LIPS assay to be a promising alternative tool for screening, diagnosing, and monitoring toxoplasmosis. In particular, detection of antibodies against BAG1 may be useful for a longitudinal seroprevalence study in suspected high-risk areas on the basis of its elevated serum concentration in the chronic phase.
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Takotsubo cardiomyopathy associated with Paragonimiasis westermani. 査読あり
Matsuoka R, Muneuchi J, Nagatomo Y, Shimizu D, Okada S, Iida C, Shirouzu H, Watanabe M, Takahashi Y, Maruyama H
Paediatrics and international child health 38 ( 4 ) 302 - 307 2018年11月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Paediatrics and International Child Health
© 2017, © 2017 Informa UK Limited, trading as Taylor & Francis Group. An 11-year-old boy collapsed during morning assembly at his junior high school. The automated external defibrillator detected ventricular fibrillation and provided shock delivery. He was successfully resuscitated and reverted to sinus rhythm. Electrocardiography showed ST-T elevation in the precordial leads. Echocardiography and angiography demonstrated akinesia of the apex and mid-wall of the left ventricle with preserved contraction of the basal segments, which suggested Takotsubo cardiomyopathy. The patient and his family had often eaten uncooked crab, and his father had a past history of infection with Paragonimiasis westermani. The patient had had a persistent cough and chest pain for several weeks. Chest radiograph showed cystic cavities in the left upper lung. Microbiological examination of the sputum demonstrated an egg of P. westermani and immunological assay showed a raised antibody titre to P. westermani. On the12th day of admission, he developed seizures, and magnetic resonance imaging demonstrated cerebral involvement. After the administration of praziquantel for 3 days, the clinical manifestations improved immediately, and echocardiography normalised within 3 weeks. The patient was discharged on the 32nd day + and follow-up was normal. Takotsubo cardiomyopathy following a potentially fatal arrhythmia is a rare cardiac complication associated with pulmonary and central nervous system infection by P. westermani.
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Cerebral Paragonimiasis With Hemorrhagic Stroke in a Developed Country. 査読あり
Kashida Y, Niiro M, Maruyama H, Hanaya R
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 27 ( 10 ) 2648 - 2649 2018年10月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Stroke and Cerebrovascular Diseases
© 2018 Elsevier Ltd Paragonimiasis is a food-borne parasitic disease caused by Paragonimus lung flukes, which are epidemic in Asia. Cerebral paragonimiasis accounts for <1% of symptomatic paragonimiasis but is the most common extrapulmonary infection. Cerebral paragonimiasis often mimics stroke and sometimes causes severe neurological sequelae. A 61-year-old woman was admitted to the hospital for severe headache. A head computed tomography scan revealed intracerebral hemorrhage with subarachnoid hemorrhage. The patient also had lesions in the lungs. She frequently ate Japanese mitten crab. Peripheral blood examination results of increased eosinophilia and immunological testing results confirmed the diagnosis of Paragonimus westermani infection. The patient was successfully treated with praziquantel as the first-line agent. Cerebral paragonimiasis is currently rare in developed countries; however, it is an important disease to consider.
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Ohno T, Kai T, Miyasaka Y, Maruyama H, Ishih A, Kino H
Parasitology international 67 ( 4 ) 357 - 361 2018年8月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Parasitology International
© 2018 Elsevier B.V. Hymenolepis diminuta is a parasitic tapeworm of the rat small intestine and is recognized as a useful model for the analysis of cestode-host interactions. In this study, we analyzed factors affecting the biomass of the tapeworm through use of rat strains carrying genetic mutations, namely X-linked severe combined immunodeficiency (xscid; T, B and NK cells deficiency), nude (rnu; T cell deficiency), and mast cell deficient rats. The worm biomass of F344-xscid rats after infection with 5 cysticercoids was much larger than control F344 rats from 3 to 8 weeks. The biomass of F344-rnu rats was also larger than the controls, but was intermediate between F344-xscid and control rats. These observations demonstrated that host immunity can control the maximal tapeworm biomass, i.e., carrying capacity, of the rat small intestine. Both T cell and other immune cells (B and NK cells) have roles in determining the carrying capacity of tapeworms. Total worm biomass and worm numbers in mast cell deficient rats (WsRC-Ws/Ws) were not significantly different from control WsRC-+/+ rats after 3 and 6 weeks of primary infection. Mast cell deficient rats displayed reinfection resistance for worm biomass but not worm expulsion. These findings suggest that the mast cell has a role for controlling the biomass of this tapeworm in reinfection alone, but does not affect the rate of worm expulsion. Overall, our findings indicate that the mast cell is not a major effector cell for the control of the carrying capacity of tapeworms. The identity of the major effector cell remains unknown.
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Wang, Z., Shibata, M., Nguyen, Y.T.H., Hayata, Y., Nonaka, N., Maruyama, H., Yoshida, A.
Parasitology international 67 ( 5 ) 622 - 626 2018年6月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Parasitology International
© 2018 Elsevier B.V. Ascarid Larva Migrans Syndrome (ascarid LMS) is a clinical syndrome in humans, caused by the migration of animal roundworm larvae such as Toxocara canis, Toxocara cati and Ascaris suum. Humans may acquire infection by ingesting embryonated eggs, or infective larvae of these parasites in contaminated meat and organ meats. To detect these pathogenic contaminations, a novel nested multiplex PCR system was developed. Our novel nested multiplex PCR assay showed specific amplification of T. canis, T. cati and Ascaris spp. Detection limit of the nested multiplex PCR was tested with serial dilution of T. canis, T. cati or A. suum genomic DNA (gDNA) from 100 pg to 100 ag and found to be 10 fg, 1 fg and 100 fg, respectively. When larvae were spiked into chicken liver tissue, DNA of T. canis and A. suum was detected from the liver spiked with a single larva, while the assay required at least 2 larvae of T. cati. Moreover, the ascarid DNA was detected from the liver of mice infected with 100 and 300 eggs of T. canis, T. cati or A. suum. This nested multiplex PCR assay could be useful for the detection of contamination with ascarid larvae in meat and organ meats.
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Nakamura-Uchiyama F, Katanami Y, Kikuchi T, Takaya S, Kutsuna S, Kobayashi T, Mizuno Y, Hasegawa T, Koga M, Yoshimura Y, Hasegawa C, Kato Y, Kimura M, Maruyama H, Research Group on Chemotherapy of Tropical Diseases, Japan.
Travel medicine and infectious disease 22 40 - 45 2018年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Travel Medicine and Infectious Disease
© 2018 Elsevier Ltd Background: The Research Group on Chemotherapy of Tropical Diseases, Japan, introduced artemether–lumefantrine (AL) in late 2002, mainly for treating uncomplicated Plasmodium falciparum malaria. Because AL was on the market in Japan in March 2017, the effectiveness and safety of AL were analyzed to help medical personnel use AL optimally. Methods: Case report forms submitted by the attending physicians were analyzed. When necessary, direct contact with the attending physicians was made to obtain detailed information. Results: Effectiveness analysis was performed for 62 cases and safety analysis was performed for 66 cases. In P. falciparum malaria, the overall cure rate was 91.1% (51/56), of which the cure rates for Japanese and non-Japanese patients were 82.1% (23/28) and 100% (28/28), respectively. The successfully treated cases included severe P. falciparum malaria, with parasite densities exceeding 500,000/μL. Adverse events were reported in 14 patients, including delayed hemolytic anemia which occurred in the top four highest parasitemic cases. Conclusions: AL treatment failure in P. falciparum malaria may not be rare among non-immune individuals, including Japanese. The possibility of delayed hemolytic anemia, which occurs preferentially in high parasitemic cases, should be considered following AL treatment.
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Hasegawa C, Kudo M, Maruyama H, Kimura M
Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 24 ( 3 ) 216 - 219 2018年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Infection and Chemotherapy
© 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases Delayed haemolytic anaemia has been reported in association with intravenous artesunate treatment in patients with severe Plasmodium falciparum malaria, and furthermore, oral artemisinin-based combination therapies including artemether-lumefantrine (AL) have also been incriminated. However, definite cases of delayed haemolytic anaemia associated with AL appear to be scarce, as reported cases were often treated concomitantly with other anti-malarials. In this study, we report a severe case of delayed haemolytic anaemia following AL alone in a Japanese traveller with severe parasitaemia caused by numerous P. falciparum parasites and a few P. vivax parasites. We also stress the need by further studies to differentiate between delayed haemolytic anaemia and blackwater fever, the latter being another malaria-related haemolytic condition, more clearly than they are now.
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Nagayasu E., Aung M., Hortiwakul T., Hino A., Tanaka T., Higashiarakawa M., Olia A., Taniguchi T., Win S., Ohashi I., Odongo-Aginya E., Aye K., Mon M., Win K., Ota K., Torisu Y., Panthuwong S., Kimura E., Palacpac N., Kikuchi T., Hirata T., Torisu S., Hisaeda H., Horii T., Fujita J., Htike W., Maruyama H.
Scientific reports 7 ( 1 ) 4844 2017年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Scientific Reports
© 2017 The Author(s). Humans and dogs are the two major hosts of Strongyloides stercoralis, an intestinal parasitic nematode. To better understand the phylogenetic relationships among S. stercoralis isolates infecting humans and dogs and to assess the zoonotic potential of this parasite, we analyzed mitochondrial Cox1, nuclear 18S rDNA, 28S rDNA, and a major sperm protein domain-containing protein genes. Overall, our analyses indicated the presence of two distinct lineages of S. stercoralis (referred to as type A and type B). While type A parasites were isolated both from humans and dogs in different countries, type B parasites were found exclusively in dogs, indicating that the type B has not adapted to infect humans. These epidemiological data, together with the close phylogenetic relationship of S. stercoralis with S. procyonis, a Strongyloides parasite of raccoons, possibly indicates that S. stercoralis originally evolved as a canid parasite, and later spread into humans. The inability to infect humans might be an ancestral character of this species and the type B might be surmised to be an origin population from which human-infecting strains are derived.
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小腸アニサキス症の2例
森紘一朗，佐原利典，藤田裕晃，中村（内山）ふくみ，大西健児，丸山治彦
Clinical Parasitology 2017年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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熱帯病治療薬研究班の登録患者からみたわが国の輸入熱帯病・寄生虫症の動向
丸山治彦，加藤康幸，古賀道子，菊地 正，木村幹男，熱帯病治療薬研究班
Clinical Parasitology 2017年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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熱帯病治療薬研究班の登録患者からみたわが国の輸入熱帯病・寄生虫症の動向
丸山治彦，加藤康幸，古賀道子，菊地 正，木村幹男，熱帯病治療薬研究班
Clinical Parasitology 2017年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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小腸アニサキス症の2例
森紘一朗，佐原利典，藤田裕晃，中村（内山）ふくみ，大西健児，丸山治彦
Clinical Parasitology 2017年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Uni S, Fukuda M, Ogawa K, Lim YA, Agatsuma T, Bunchom N, Saijuntha W, Otsuka Y, Bhassu S, Mat Udin AS, Zainuri NA, Omar H, Nakatani J, Matsubayashi M, Maruyama H, Ramli R, Azirun MS, Takaoka H
Parasitology international 66 ( 5 ) 593 - 595 2017年10月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Parasitology International
© 2017 Elsevier B.V. An 11-year-old boy living in Otsu City, Shiga Prefecture, Kansai Region, Western Honshu, Japan had zoonotic onchocercosis. The patient developed a painful swelling on the little finger of his left hand. The worm detected in the excised mass had external transverse ridges but did not have inner striae in the cuticle. On the basis of the parasite's histopathological characteristics, the causative agent was identified as a female Onchocerca dewittei japonica (Spirurida: Onchocercidae). The species of the filarial parasite was confirmed by sequencing the cox1 gene of the parasite. The Japanese wild boar Sus scrofa leucomystax is a definitive host for O. dewittei japonica, which is then transmitted by blackflies as the vector to humans. The current case described occurred in the Kansai Region, Western Honshu, where such infections were previously not reported.
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糞線虫症研究の新展開
長安英治, 菊池泰生, 丸山治彦
医学と薬学 2017年10月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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糞線虫症研究の新展開
長安英治, 菊池泰生, 丸山治彦
医学と薬学 2017年10月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Imported malaria in pregnant women experienced in Japan. 査読あり
Kimura M, Koga M, Hasegawa C, Mutoh Y, Kato Y, Maruyama H.
J Infect Chemother. 23 ( 8 ) 545 - 549 2017年8月
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Daigo Tsubokawa, Takeshi Hatta, Taisei Kikuchi, Hiroki Maeda, Fusako Mikami, M Abdul Alim, Haruhiko Maruyama, Naotoshi Tsuji
International journal for parasitology 47 ( 8 ) 501 - 509 2017年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal for Parasitology
© 2017 Australian Society for Parasitology The secretory EF-hand Ca ++ -binding proteins act as calcium signaling molecules for control of cell functions, but those proteins from parasitic helminths are poorly understood. Here, we have identified and characterized an EF-hand Ca ++ -binding protein from the rodent nematode, Strongyloides venezuelensis, termed ‘venestatin’, which is highly conserved in Strongyloides spp. Canonical two EF-hand domains and a signal peptide are present in venestatin. A gel mobility shift assay and Ruthenium red staining indicated that the recombinant venestatin possesses binding ability with Ca ++ ions. Endogenous venestatin was seemingly localized in the hypodermis and gut of the worms and was found in the excretory-secretory products. Quantitative reverse transcription-PCR data showed that venestatin-specific transcript was upregulated in the parasitic stages of S. venezuelensis, and the upregulation occurred promptly after larval invasion through the host's skin, but not in the case of in vitro incubation. Immunization of mice with recombinant venestatin caused a 55% reduction in larval migration to the lungs, and lung hemorrhaging was mild compared with non-immunized groups, suggesting that anti-venestatin sera may interfere with larval migration from skin to lung. Our results suggest that venestatin is secreted from the hypodermis and gut of S. venezuelensis, and has pivotal roles in larval migration.
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Tsuchido Y, Nakamura-Uchiyama F, Toyoda K, Iwagami M, Tochitani K, Shinohara K, Hishiya N, Ogawa T, Uno K, Kasahara K, Ouji Y, Kano S, Mikasa K, Shimizu T, Yoshikawa M, Maruyama H
The American journal of tropical medicine and hygiene 96 ( 5 ) 1185 - 1189 2017年5月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：American Journal of Tropical Medicine and Hygiene
Copyright © 2017 by The American Society of Tropical Medicine and Hygiene. Recently, reports of delayed hemolytic anemia after treatment with artemisinin and its derivatives have emerged. Here we report two cases of delayed hemolytic anemia in a patient with severe falciparum malaria after treatment with oral artemether-lumefantrine (AL). The first patient, a 20-year-old Japanese male student, was diagnosed with falciparum malaria and was administered AL. As having a high parasitemia rate (20.6%) was the only severe malaria criterion met in this case and his general condition was stable, we continued with AL treatment. Despite disappearance of malarial parasites after 4 days of AL administration, a persistent fever remained. On days 13 and 16, a diagnosis of hemolytic anemia was made (lactate dehydrogenase [LDH]: 1,466 U/L, hemoglobin [Hb] : 7.2 g/dL). A blood smear at that time revealed no parasites. He recovered naturally from delayed hemolysis. The second patient, a 27-year-old Japanese female student, was diagnosed with falciparum malaria (parasitemia: 4.5%) and treated initially with oral quinine hydrochloride and doxycycline. The following day, parasitemia increased to 7.9% and oral AL was initiated. She was discharged on day 4 after achieving parasite clearance and afebrility. However, on day 5, fever (body temperature > 38C) recurred, and on day 11, a diagnosis of hemolytic anemia was made (LDH: 712 U/L, Hb: 8.8 g/dL). A follow-up confirmed that her condition improved gradually. AL treatment of severe malaria can cause delayed hemolytic anemia. Patients should be followed up for up to 4 weeks to detect signs of hemolysis and provide appropriate symptomatic treatment.
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Nguyen, Y.T.H., Wang, Z., Maruyama, H., Horii, Y., Nonaka, N., Yoshida, A.
Journal of Food Safety 37 ( 2 ) 2017年5月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Food Safety
© 2016 Wiley Periodicals, Inc. Ascarid larva migrans syndrome (ascarid LMS) is caused by ascarid roundworms including Ascaris suum. In East Asia, ascarid LMS has been considered as a food-borne disease in adulthood who has the dietary habitat of consuming raw or lightly cooked meat and organ meats. To evaluate the potential risk of A. suum infection from these foods, Ascaris specific real-time PCR was developed. The assay could constantly detect A. suum DNA up to 10 fg. Its specificity was confirmed by non-amplification with Toxocara canis and Toxocara cati DNA. A. suum DNA could be amplified from not only a single larva but also mouse liver spiked with a larva. Moreover, the assay could detect A. suum DNA in experimentally infected mouse liver, and showed higher sensitivity than a conventional digestion method. This real-time PCR assay would be useful for detecting the A. suum larval contamination in meat and organ meats. Practical applications: It has been considered that one of the most important risk factors for ascarid LMS in humans is the consumption of raw or undercooked meat or organ meats of domestic animals infected with Ascaris suum. Thus, we developed the novel real-time PCR with the high sensitivity and specificity in order to specifically detect A. suum DNA from animal tissues. This assay can be applied to the meat inspection procedure for the identification of parasite larval contamination that may adversely impact on public health as well as on animal health and welfare.
DOI： 10.1111/jfs.12301
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Kambe, D., Takeoka, K., Ogawa, K., Doi, K., Maruyama, H., Yoshida, A., Suenaga, T., Kageyama, T.
Multiple sclerosis and related disorders 13 116 - 118 2017年4月
記述言語：英語 掲載種別：症例報告 出版者・発行元：Multiple Sclerosis and Related Disorders
© 2017 Elsevier B.V. A 53-year-old woman was admitted to the department of neurology in Tenri Hospital because of progressive thoracic myelitis a month after she had eaten uncooked bovine liver. A previous episode of right optic neuritis and a positive test for serum anti-aquaporin-4 antibodies indicated a diagnosis of neuromyelitis optica spectrum disorders. Although the patient initially recovered with the reduction of anti-aquaporin-4 antibodies during treatment with intravenous methylprednisolone infusion and plasma exchange, her neurological symptoms deteriorated soon after the completion of plasma exchange. Western blotting analysis detected anti-Toxocara canis antibodies in the serum; thus, the patient underwent oral albendazole treatment. This resulted in the alleviation of her symptoms. We therefore consider that rigorous investigation should be encouraged to detect rare pathogens including parasites in cases of treatment-resistant neuromyelitis optica spectrum disorders.