The current status of neglected tropical diseases in Japan: A scoping review.

Little attention has been paid to neglected tropical diseases (NTDs) in high-income countries and no literature provides an overview of NTDs in Japan. This scoping review aims to synthesize the latest evidence and information to understand epidemiology of and public health response to NTDs in Japan. Using three academic databases, we retrieved articles that mentioned NTDs in Japan, written in English or Japanese, and published between 2010 and 2020. Websites of key public health institutions and medical societies were also explored. From these sources of information, we extracted data that were relevant to answering our research questions. Our findings revealed the transmission of alveolar echinococcosis, Buruli ulcer, Chagas disease, dengue, foodborne trematodiases, mycetoma, scabies, and soil-transmitted helminthiasis as well as occurrence of snakebites within Japan. Other NTDs, such as chikungunya, cystic echinococcosis, cysticercosis, leishmaniasis, leprosy, lymphatic filariasis, rabies, and schistosomiasis, have been imported into the country. Government agencies tend to organize surveillance and control programs only for the NTDs targeted by the Infectious Disease Control Law, namely, echinococcosis, rabies, dengue, and chikungunya. At least one laboratory offers diagnostic testing for each NTD except for dracunculiasis, human African trypanosomiasis, onchocerciasis, and yaws. No medicine is approved for treatment of Chagas disease and fascioliasis and only off-label use drugs are available for cysticercosis, opisthorchiasis, human African trypanosomiasis, onchocerciasis, schistosomiasis, and yaws. Based on these findings, we developed disease-specific recommendations. In addition, three policy issues are discussed, such as lack of legal frameworks to organize responses to some NTDs, overreliance on researchers to procure some NTD products, and unaffordability of unapproved NTD medicines. Japan should recognize the presence of NTDs within the country and need to address them as a national effort. The implications of our findings extend beyond Japan, emphasizing the need to study, recognize, and address NTDs even in high-income countries.

Yeast diversity during the spontaneous fermentation of wine with only the microbiota on grapes cultivated in Japan.

Making wine via spontaneous fermentation without sulfur dioxide and commercial yeast (spontaneous winemaking) is increasing in recent year, but there is scant research regarding microbial communities present in Japan during spontaneous winemaking using culture-independent molecular methods. We analyzed fungal communities and populations during laboratory-scale spontaneous winemaking using sterilized labware to avoid winery-resident microbes. In the spontaneous fermentation of four grape varieties (Pinot Noir, Riesling, Koshu, and Koshusanjaku) grown in the same Japanese vineyard, our analysis of yeast and other fungal species by next-generation sequencing based on the ITS1 region demonstrated that Saccharomyces cerevisiae was eventually dominant in seven of 12 fermentation batches (three replications for each grape variety), whereas non-Saccharomyces species (e.g., Schizosaccharomyces japonicus, Lachancea dasiensis, and Hanseniaspora valbyensis) became dominant in four batches at the end of fermentation. In another batch, lactic acid bacteria (LAB) became dominant and the fermentation remained incomplete. Diverse microbes were involved in the spontaneous fermentation (particularly in Koshusanjaku), indicating that residual sugar remained and lactic and acetic acid largely increased. Compared to the control wine made with SO2 and commercial yeast, the concentration of lactic acid was 47-fold higher in the must dominated by L. dasiensis, and the concentrations of acetic acid and lactic acid were 10-fold and 20-fold higher in the must dominated by LAB, respectively. Even when indigenous S. cerevisiae became dominant, the finished wines obtained high sensory-analysis scores for complexity but low scores for varietal typicality, indicating the risk of fermentation with unselected wild yeast on the grapes grown in Japan.

Lessons From the Wrong Isolation Policy Violating Human Rights for Leprosy in Japan.

Leprosy, caused by Mycobacterium leprae , is one of the so-called "neglected tropical diseases" and is found today mainly in Africa, Asia and South America. Although oral antibiotics capable of curing leprosy are now available, the disease is still misunderstood and feared by the public because of the unsightly deformities that it may cause. In Japan, leprosy has been present since the 8th century and was regarded as a hereditary disease; people avoided marrying into a family with a member affected by leprosy. At the beginning of the 20th century, the Japanese government instituted a policy of lifetime quarantine of individuals with leprosy to eradicate the disease, thereby purposely disseminating negative and inaccurate perceptions of the disease as deadly and highly contagious and fostering a long-lasting prejudice among the general public towards those affected. Even after effective treatments became available, the government continued quarantining patients until 1996. The government has since then apologized to the patients for violating their constitutionally guaranteed human rights. Children with leprosy and children born to parents with leprosy were also victims of the policy and prejudice created. We describe herein the history of leprosy-related policies in Japan to emphasize the importance of balancing public health policy with human rights.

[Suna no utsuwa (Castle of Sand): A Film Concerning Hansen's Disease].

Hansen's disease (also known as leprosy) is a chronic infection that is caused by Mycobacterium leprae. It predominantly affects the peripheral nerves, skin, eyes, and nasal mucosa, Following the development of effective treatment with diaphenylsulfone followed by rifampicin, and clofazimine since 1940s, Hansen's disease has been eradicated in Japan. However, the longstanding stigma surrounding this disease, exacerbated partly by forced isolation and other regulations introduced in 1930s, has delayed the abrogation of these regulations. The influence of two Japanese films, namely Kojimanoharu (no English title; "Spring in Islets") (1940) and Casle of Sand (1974), inspired by these events and addressing the concerns regarding this disease, are discussed.

Hansen's disease (leprosy) in Japan, 1947-2020: an epidemiologic study during the declining phase to elimination.

OBJECTIVES: Leprosy, or Hansen's disease was a major public health problem in Japan in the early 20th century. Today, the number of new cases has decreased significantly. We aimed to investigate the trends of leprosy in Japan over the past 73 years and the challenges faced in recent years. METHODS: We assessed the data on newly registered cases of leprosy from 1947 to 2020. RESULTS: A total of 10,796 newly registered cases of leprosy were reported during the study period, of which 7573 were registered in mainland Japan, 2962 in Okinawa, and 250 were of foreign origin. Most autochthonous cases were born before 1950 in mainland Japan and before 1975 in Okinawa. The number of nonautochthonous cases surpassed that of autochthonous cases in 1992. Nonautochthonous cases originated from 26 countries, particularly Brazil and the Philippines. Three cases of antimicrobial resistance have been detected among nonautochthonous cases since 2004. CONCLUSION: Our data suggest that ongoing transmission of leprosy likely ceased in the 1940s in mainland Japan and in the 1970s in Okinawa. With the recent rise of nonautochthonous cases with globalization, continuous surveillance and efforts to maintain leprosy services within the country are necessary even after reaching the state of elimination.

Newly or switching effect of a selective EP2 agonist on intraocular pressure in Japanese patients with open-angle glaucoma.

PURPOSE: To evaluate omidenepag isopropyl (OMDI) for its efficacy in intraocular pressure control (IOP) and adverse reactions following administrations in Japanese patients with open-angle glaucoma (OAG) over a 3-month period. STUDY DESIGN: Retrospective observational study. SUBJECTS AND METHODS: Group 1 included untreated OAG patients, Group 2 included OAG patients treated with prostaglandin F (FP) receptor agonists (monotherapy) and Group 3 included OAG patients treated with multidrug therapy, including FP receptor agonists. OMDI was newly administered in Group 1, and FP receptor agonists were switched to OMDI in Group 2. In Group 3, all other ocular hypotensive medications were continued except FP receptor agonists. IOP changes were examined, and adverse reactions were retrieved from the medical records. RESULTS: Group 1 included 32 eyes, Group 2, 20 eyes and Group 3, 17 eyes. In Group 1, the baseline IOP was 15.7 mmHg (95% confidence interval [CI] 14.7-16.8 mmHg). After eyedrop treatment, the IOP was 14.1 mmHg (P < 0.001) at 1 month and 13.7 mmHg (P < 0.001) at 3 months. By contrast, in Group 2 and Group 3, switching FP receptor agonists to OMDI did not result in significant IOP changes (P ≥ 0.71). Six patients developed adverse reactions (hyperemia, headache, ocular pain, and swollen eyelids). CONCLUSIONS: New administration of OMDI significantly reduced the IOP. Furthermore, the IOP did not change after switching from FP receptor agonists to OMDI, including multidrug therapy. OMDI can be used as a first-line drug and is comparable to FP receptor agonists in Japanese patients with OAG.

Death and Survival of Patients with Hansen's Disease in Colonial Korea.

The purpose of this research is to describe how Hansen's disease patients experienced the modern system of control of Hansen's disease introduced by Japan, and the inimical attitude of society against them in colonial Korea. The study also seeks to reveal the development of the system to eliminate Hansen's disease patients from their home and community to larger society and leprosarium in this era. Sorokdo Charity hospital (SCH), a hospital for Hansen's disease patients, was built in 1916, and vagrant Hansen's disease patients began to be isolated in this hospital beginning in 1917 by the Japanese Government-General of Korea (JGGK). Once the police detained and sent vagrant Hansen's disease patients to SCH, stigma and discrimination against them strengthened in Korean society. Because of strong stigma and discrimination in Korean society, Hansen's disease patients suffered from daily threats of death. First, their family members were not only afraid of the contagiousness of Hansen's disease but also the stigma and discrimination against themselves by community members. If a family had a Hansen's disease patient, the rest of community members would discriminate against the entire family. Furthermore, because Hansen's disease patients were excluded from any economic livelihood such as getting a job, the existence of the patients was a big burden for their families. Therefore, many patients left their homes and began their vagrancy. The patients who could not leave their homes committed suicide or were killed by their family members. The victims of such deaths were usually women, who were at the lower position in the family hierarchy. In the strong Confucian society in Korea, more female patients were killed by themselves than male patients. Moreover, all of patients victims in the murder were women. This shows that the stigma and discrimination against Hansen's disease patients within their families were stronger against women than men. Strong stigma and discrimination made the patients rely on superstition such as cannibalism. Patients believed that there were not any effective medicine. There were a few reports of patients who were cured, and many were treated with chaulmoogra oil in the modern Hansen's disease hospitals. Eating human flesh was known as a folk remedy for Hansen's disease. As such, patients began to kill healthy people, usually children, to eat their flesh. Increased stigma led to increased victims. Hansen's disease patients who left their homes faced many threats during their vagrancy. For survival, they established their own organizations in the late 1920's. The patients who were rejected to be hospitalized in the Western Hansen's disease hospital at Busan, Daegu, and Yeosu organized self-help organizations. The purpose of these organizations was first to secure the medicine supply of chaulmoogra oil. However, as stigma and discrimination strengthened, these organizations formed by Hansen's disease patients demanded the Japanese Government-General of Korea to send and segregate them on Sorok island. They did not know the situation of the inside of this island because news media described it as a haven for patients, and very few patients were discharged from this island to tell the truth. On this island, several hundreds of patients were killed by compulsory heavy labor, starvation, and violence. They were not treated as patients, but as something to be eliminated. Under strong suppression on this island, the patients resisted first by escaping this island. However, in 1937, some patients tried to kill a Korean staff but failed. Attempted murderers were all put in the jail, also located on this island. In 1941, a patient murdered another patient who had harassed other patients, and in 1942, Chunsang Lee, a patient, killed the director of Sorok island. These instances show that there was a system to eliminate Hansen's disease patients in colonial Korea.

Three new species of Tridentella Richardson, 1905 (Isopoda: Cymothoida: Tridentellidae) from New Caledonia.

Three new species of Tridentella Richardson, 1905 are described from the New Caledonia region. All three species are smooth bodied or largely smooth bodied, and all were collected from the shelf around New Caledonia at depths from 150-760 metres. Tridentella palmata sp. nov. is characterised by pereopod 4 having numerous large robust setae on the carpus and an exceptionally long dactylus (7.0 times as long as proximal width); Tridentella katlae sp. nov. is the only species in the genus with medially united eyes that fill the head in dorsal view; Tridentella magna sp. nov. is the largest species in the genus (36 mm) and can be identified by the head having an anterior submarginal ridge and three submarginal tubercles on the poster margin. Tridentella takedai Nunomura 2006 (off Arasaki, Hokusuka-Shi, Kyushu, Japan) is formally transferred to Alcirona Hansen, 1905, forming Alcirona takedai (Nunomura, 2006) comb. nov.

Prof. Masao Ota.

Masao Ota was a Professor of Dermatology at Tokyo Imperial University. He is known to dermatologists around the world as the researcher who identified Nevus of Ota. He is also known for his research on Hansen's Disease. He was critical of the forced isolation policy and the sterilization law. He dreamt of developing chemotherapeutic measures and dedicated himself to cultivating Mycobacterium leprae. Among his accomplishments, those in the area of medical mycology are particularly remarkable. His discovery of Microsporum ferrugineum, his proposal for Trichophytia pompholyciformis, and his work on Ota-Langeron taxonomy based on the findings on fungus colonies are highly regarded and earned him the Ordre Royale de la Legion D'honneur. His accomplishments in the field of mycology are numerous; he has published a total of 39 research papers mostly in foreign languages. He was a leading world-class medical mycologist of his day. This review introduces some of his accomplishments and some episodes in his life.Furthermore, Masao Ota had a detailed knowledge of art and culture. Under the pseudonym of Kinoshita Mokutaro, he wrote poems, plays, and novels. He was also a painter. Particularly, his paintings in botany during his later years were published in the book "One Hundred Flower Sketches" after his death.Ota said, "The consequence of both science and art is global and humanitarian." He was one of the greatest men of culture in his time.

A Modern History of 'Imperial Medicine' Surrounding Hansen's Disease: Strategies to Manage Public Opinion in Modern Japanese Media.

The purpose of this study is to understand the reality of imperial medicine by exploring the strategic attitude of the Japanese authority targeting the public who were not patients of Hansen's disease. For this purpose, this study examines the mass media data related to Hansen's disease published in Korea and Japan during the Japanese colonial rule. Research on Hansen's disease can be divided into medical, sociohistorical, social welfare, and human rights approach. There are medical studies and statistics on the dissemination of medical information about Hansen's disease and management measures, the history of the management of the disease, guarantee of the rights of the patients and the welfare environment, and studies on the autobiographical, literary writings and oral statements on the life and psychological conflicts of the patients. Among existing research, the topics of the study on Hansen's disease under the Japanese colonial rule include the history of the Sorokdo Island Sanatorium, investigation on the forced labor of the patients in the island, human rights violations against the patients, oral memoirs of the patients and doctors who practiced at that time. All of these studies are important achievements regarding the research on the patients. An important study of Hansen's disease in modern Japan is the work of Hujino Utaka, which introduces the isolation of and discrimination against the patients of Hansen's disease. Hujino Utaka's study examines the annihilation of people with infectious diseases in Japan and its colonies by the imperial government, which was the consequence of the imperial medical policies, and reports on the isolation of Hansen's disease patients during the war. Although these researches are important achievements in the study of Hansen's disease in modernity, their focus has mainly been on the history of isolation and exploitation in the Sorokdo Island Sanatorium and discrimination against the patients within the sanatorium, which was controlled by the director of the sanatorium. Consequently, the research tends to perceive the problem within the frame of antagonism between the agent of imperialism and the victims of exploitation by the hands of imperialism. Hence, it has limitations in that it has not fully addressed the problem of the people who were not Hansen's disease patients and as such, existed somewhere in between the two extremes in the process of administering medicine under the imperial rule. The purpose of this study is to identify the direction of imperial medicine in the history of Hansen's disease in Japan and to comprehend the characteristics of policy on Hansen's disease developed by Mitsuda Kensuke, who was behind the policy of imperial medicine, and examine the process of imperial medicine reaching out to the people (of Japan and its colonies). To achieve the goal, this study explores how the agent of imperial medicine gain the favor the public, who are not Hansen's disease patients, by means of the mass media. Specifically, this paper examines data in the Japanese language related to Korean patients of Hansen's disease including the mass media data on Hansen's disease in the source book titled The Collection of Data on Hansen's Disease in Joseon under the Colonial Rule(8 volumes) compiled by Takio Eiji, which has not been studied until now. It also reviews the cultural and popular magazines published in Japan and Joseon at that time.

[A Study on the Entering and Out-going Trends at Japan's National Hansen's Disease Sanatoriums].

A Hansen's disease (HD) policy began in Japan with the enactment of the No. 11 Act on Leprosy (1907 law No. 11), which was the first leprosy prevention law in Japan in 1907. Results of the law included the enforcement of regulations of the stated law and the establishment of Prefectural Allied (National) HD Sanatoriums in 1909. This policy continued until the "leprosy prevention law" abolition in 1996, and about 35,000 people were placed in isolation; however, its entering and out-going trends are not clear yet. The purpose of this research is to clarify the actual condition of the Japanese HD policy. We added up the number of individuals entering and leaving the sanatorium from 1909 to 2010. This information was collected from annual reports and the internal material from each national sanatorium. In the results, the number of general residents (new, re-entering, transferring from other sanatoriums) and the number of general out-going persons (transferring to another sanatorium, formal discharge, informal discharge including escape and wrong diagnosis, and others) were all totaled as the running number during the 102 year span, in addition to being added to the deaths. The results show that the number of general residents was 56,575 people and the number of general out-going persons was 54,047 people (death: 25,200 people; change of sanatorium: 4,350 people; formal discharge: 7,124 people; informal discharge including escape: 12,378 people; wrong diagnosis: 310 people; others: 4,685 people). Based on the details of each leprosy prevention law, the results for the first "1907 law No. 11" show that the number of general residents was 12,673 people and the number of general out-going persons was 9,070 people. The "1931 leprosy prevention law" results show that the number of general residents was 31,232 people and the number of general out-going persons was 23,354 people. The "1953 leprosy prevention law" results show that the number of general inmates was 12,098 people and the number of general out-going persons was 18,159 people. The "1996 law about repeal of leprosy prevention law" results show that the number of general residents was 572 people and the number of general out-going persons was 3,464 people. We can clarify the number of general residents and the number of general out-going persons in the National HD Sanatoriums in Japan.

Detection of Multiple Budding Yeast Cells and a Partial Sequence of 43-kDa Glycoprotein Coding Gene of Paracoccidioides brasiliensis from a Case of Lacaziosis in a Female Pacific White-Sided Dolphin (Lagenorhynchus obliquidens).

Lacaziosis, formerly called as lobomycosis, is a zoonotic mycosis, caused by Lacazia loboi, found in humans and dolphins, and is endemic in the countries on the Atlantic Ocean, Indian Ocean and Pacific Ocean of Japanese coast. Susceptible Cetacean species include the bottlenose dolphin (Tursiops truncatus), the Indian Ocean bottlenose dolphin (T. aduncus), and the estuarine dolphin (Sotalia guianensis); however, no cases have been recorded in other Cetacean species. We diagnosed a case of Lacaziosis in a Pacific white-sided dolphin (Lagenorhynchus obliquidens) nursing in an aquarium in Japan. The dolphin was a female estimated to be more than 14 years old at the end of June 2015 and was captured in a coast of Japan Sea in 2001. Multiple, lobose, and solid granulomatous lesions with or without ulcers appeared on her jaw, back, flipper and fluke skin, in July 2014. The granulomatous skin lesions from the present case were similar to those of our previous cases. Multiple budding and chains of round yeast cells were detected in the biopsied samples. The partial sequence of 43-kDa glycoprotein coding gene confirmed by a nested PCR and sequencing, which revealed a different genotype from both Amazonian and Japanese lacaziosis in bottlenose dolphins, and was 99 % identical to those derived from Paracoccidioides brasiliensis; a sister fungal species to L. loboi. This is the first case of lacaziosis in Pacific white-sided dolphin.

[Hansen's Disease Patients in Yunosawa Village and Their Relationship with the Wider Community: 1869-1941].

This paper explores the history of Yunosawa Village for Hansen's disease patients in Kusatsu Town, which is famous for its hot springs and located in a mountainous area of Gunma Prefecture, Japan. Yunosawa Village was initially formed by Kusatsu Town government as a settlement for a small number of patients in 1869, but later became the biggest "open leprosy colony" for Hansen's disease patients in modern Japan. Patients in Yunosawa gradually constructed their own regional community and expanded their presence in Kusatsu as part of the town. Although townspeople in Kusatsu made several attempts to remove patients in Yunosawa to a more remote area away from the town center so that they would be out of sight of visitors, townspeople in Kusatsu had a long history of treating Hansen's disease patients as customers of the hot springs, which enabled them to understand the nature of the disease through their own experience. This "folk epidemiology" created a "symbiotic" relationship between patients in Yunosawa and townspeople for nearly 60 years until the national government finally closed Yunosawa in 1941.

[On the present and future of Japanese Leprosariums--the case of Oshima-seishoen Sanatorium].

In all thirteen national sanatorium in Japan, the number of patients have gradually declined year by year. Although it has been long discussed about maintenance and utilization of facilities in the future, clear and specific plans are still not sufficient. Especially Oshima-seishoen sanatorium, Oshima island is an isolated island located off the coast of Takamatsu port. It is very different from the other Leprosy sanatoriums in that there are no general population other than patients and officials of the sanatorium. So it is very difficult to have outlooks of the future of this sanatorium. In the conversation with the patients, two serious concerns have been raised. Whether patients will be provided support and treatment throughout life. The other one is whether the government would manage the ossuary permanently under the responsibility for the isolation policy of leprosy patients. These two points are also written in promotion measures of Oshima formulated by "Meeting to consider the future of Oshima", that was established in 2013 proposed by Takamatsu city authorities. In the situation of aging of patients accelerating, I considered that to promise these two points are the top priority.

A case of stranded Indo-Pacific bottlenose dolphin (Tursiops aduncus) with lobomycosis-like skin lesions in Kinko-wan, Kagoshima, Japan.

Lobomycosis is a chronic fungal disease caused by the etiologic agent, Lacazia loboi, in the skin and subcutaneous tissues in humans and dolphins in tropical and transitional tropical climates. An Indo-Pacific bottlenose dolphin (Tursiops aduncus) stranded in Kagoshima, Japan, had severe skin lesions characterized by granulomatous reactions and hyperkeratosis that were similar to those of the lobomycosis, but no fungal organism was observed in the skin lesion. In this paper, we report a stranded Indo-Pacific bottlenose dolphin with lobomycosis-like lesions based on pathological examinations in Japan.

Paleopathological evidence and detection of Mycobacterium leprae DNA from archaeological skeletal remains of Nabe-kaburi (head-covered with iron pots) burials in Japan.

The Nabe-kaburi is a unique burial method, the purpose of which is shrouded in mystery. The burials were performed during the 15(th) to 18(th) centuries in eastern Japan, and involved covering the heads of the deceased with iron pots or mortars. The identification of leprosy-specific osteological lesions among some of the excavated remains has led to the suggestion that Nabe-kaburi burials were a reflection of the social stigma against certain infectious diseases, such as leprosy, tuberculosis or syphilis. However, molecular evidence for the presence of disease has been lacking. The goal of this study was to detect Mycobacterium leprae (M. leprae) DNA in archaeological human skeletal remains from Nabe-kaburi burials. The paleopathological data from three Nabe-kaburi burials were re-evaluated before small samples were taken from affected and control areas. DNA was extracted and used as a template to target the M. leprae-specific DNA using a combination of whole genome amplification, PCR analysis and DNA sequencing. M. leprae DNA fragments were detected in the two sets of skeletal remains that had also shown paleopathological evidence of leprosy. These findings provide definitive evidence that some of the Nabe-kaburi burials were performed for people affected by leprosy. Demonstration of the presence of M. leprae DNA, combined with archeological and anthropological examinations, will aid in solving the mystery of why Nabe-kaburi burials were performed in medieval Japan.