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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. Author summary: Neglected tropical diseases (NTDs) are an umbrella term for 20 diseases and disease groups recognized by the World Health Organization. Although NTDs are usually considered to be a public health problem in low- and middle-income countries, people living in high-income countries could also be affected. In this scoping review, we aimed to summarize the latest evidence and information to understand the epidemiology of and public health response to NTDs in Japan. Japan officially reported a yearly average of 340 NTD cases between 2014 and 2017; however, we found that it does not accurately reflect the current status of NTDs in the country. Our review suggests that 15 of 20 NTDs can be considered to be important public health concerns. While echinococcosis, chikungunya, dengue, and rabies are under control by law, many other NTDs are largely neglected by Japan's health systems and solely addressed by a limited number of physicians and researchers. We recommend that the Government of Japan should assume responsibility for enhancing surveillance, expanding access to diagnostics and medicines, and ensuring affordability of unapproved NTD drugs. [ABSTRACT FROM AUTHOR]

• We investigated the nationwide data of leprosy in Japan, spanning over 73 years. • Ongoing transmission ceased during the 1930s-1940s in mainland Japan and 1970s in Okinawa. • A long incubation period of leprosy was observed in patients aged >90 years. • Epidemiologic patterns of nonautochthonous cases of leprosy have been observed since 1964. • Antimicrobial-resistant cases of leprosy were detected from nonautochthonous cases. 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. We assessed the data on newly registered cases of leprosy from 1947 to 2020. 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. 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. [ABSTRACT FROM AUTHOR]

A new diabetic foot evaluation scale was proposed, using the seven domains of depth, maceration, inflammation/infection, size, tissue type of the wound bed, type of wound edge, and tunneling/undermining. This scale was named "DMIST" as an acronym from the initials of the domains. The purpose of this study was to evaluate the validity of DMIST. Secondary analysis was conducted in three investigations performed using the diabetic foot ulcer assessment scale (DFUAS) in Japan and Indonesia. Secondary analysis was assessed using DMIST, PUSH, and DESIGN for 4 weeks based on DFUAS score and photographs of diabetic foot ulcers by researchers. Concurrent validity was determined from the correlation of total DMIST scores with PUSH and DESIGN scores. Construct validity was determined by comparisons between total DMIST score and grade of the Wagner classification. Predictive validity was determined by receiver operating characteristic curve analysis for wound non‐healing 4 weeks later. Subjects comprised 35 Japanese patients and 118 Indonesian patients. Correlations of total DMIST score with PUSH and DESIGN scores were 0.831 and 0.822, respectively. Comparison of total DMIST scores with grade of the Wagner classification (Grade I vs. Grade II/III vs. Grade IV/V) was p < 0.001. Based on an area under the curve of 0.872, a DMIST score of 9 was selected as a cut‐off, offering sensitivity of 0.855 and specificity of 0.786 for wound non‐healing 4 weeks later. Our findings suggest that DMIST offers high validity. [ABSTRACT FROM AUTHOR]

Aims: To identify differences in the characteristics of patients with diabetic foot ulcers (DFUs) according to their etiological classification and to compare their healing time., Methods: Over a 4.5-year period, 73 patients with DFUs were recruited. DFUs were etiologically classified as being of neuropathic, ischemic, or neuro-ischemic origin. Descriptive analyses were performed to characterize study subjects, foot-related factors, and healing outcome and time. Duration of healing was assessed using the Kaplan-Meier method. Healing time among the three types was compared using the log rank test., Results: The number of patients manifesting neuropathic, ischemic, and neuro-ischemic ulcers was 30, 20, and 14, respectively. Differences were identified for age, diabetes duration, body mass index, hypertension, and estimated glomerular filtration rate. Patients with neuro-ischemic ulcers had better ankle-brachial index, skin perfusion pressure (SPP), and transcutaneous oxygen pressure values compared to those with ischemic ulcers. The average time in which 50% of patients had healed wounds was 70, 113, and 233 days for neuropathic, neuro-ischemic, and ischemic ulcers, respectively. Main factors associated with healing were age and SPP values., Conclusions: Based on the etiological ulcer type, DFU healing course and several patient factors differed. Failure to consider the differences in DFU etiology may have led to heterogeneity of results in previous studies on DFUs., (Copyright © 2014 Elsevier Inc. All rights reserved.)

ad hoc committee of Japanese Leprosy Association recommends revised standard treatment protocol of leprosy in Japan, which is a modification of World Health Organization's multidrug therapy (WHO/MDT, 2010). For paucibacillary (PB) leprosy, 6 months treatment by rifampicin and dapsone (MDT/PB) is enough. However, for high bacterial load multibacillary (MB) leprosy, 12 months treatment seems insufficient. Thus, (A) For MB with bacterial index (BI) > 3 before treatment, 2 years treatment by rifampicin, dapsone and clofazimine (MDT/MB) is necessary. When BI becomes negative and active lesion is lost within 2 years, no maintenance therapy is necessary. When BI is still positive, one year of MDT/MB is added (3 years in total), followed by maintenance therapy by dapsone and clofazimine until BI negativity and loss of active lesions. (B) For MB with BI < 3 or fresh MB (less than 6 months after the onset of the disease) with BI > 3, 1 year treatment by MDT/MB is necessary. When BI becomes negative and active lesion is lost within one year, no maintenance therapy is necessary. When BI is still positive or active lesion is remaining, additional therapy with MDT/MB for one more year is recommended. Brief summary of diagnosis, purpose of therapy, character of drugs, and prevention of deformity is also described.

Buruli ulcer (BU) is an emerging human disease caused by Mycobacterium ulcerans, which mainly affects the extremities. It is most endemic in sub-Saharan Africa; however, it has been reported worldwide, including in some non-tropical areas. "M. ulcerans subsp. shinshuense" is proposed as a subspecies of M. ulcerans, which have been reported from Japan and China. A total of 35 BU cases have been reported as of November 2012. Although M. ulcerans is categorized as nontuberculous mycobacteria, it has some unique characteristics that could only be observed in this bacterium. It possesses a giant virulent plasmid, composed of 174-kbp nucleotides, coding polyketide synthase to produce macrolide toxin called mycolactone. The discovery of such a linkage of plasmid and its pathogenesis has not been reported in other human disease-causing mycobacteria.

Buruli ulcer (BU) is a new emerging disease and the third most common chronic mycobacterial infection in humans, caused by Mycobacterium ulcerans. Approximately 5000 cases are reported annually from at least 33 countries around the globe, but more from the tropical nations. A total of 32 cases have been reported from Japan sporadically since 1980. None of the cases were related to international travel. Of the total reported, M. ulcerans ssp. shinshuense, a subspecies speculated to be domestic to Japan or in Asia, has been isolated from 23 cases. The mode of transmission and its incubation period remain unclear, despite several proposed hypotheses, including several vectors and cutaneous wound as port of entry for the pathogen. M. ulcerans invades the skin, subcutaneous tissue, fascia and eventually forms extensive ulceration. Smear, culture, histopathology and polymerase chain reaction are established diagnostic tools to identify M. ulcerans. Multiple antimicrobial therapy is a commonly used therapeutic method, but patients often need extensive debridement and, at times, skin grafting, especially when diagnosis is delayed. Thus, expanding a system for improved awareness and diagnosis in Japan and Asia is important, together with elucidating the candidate vector and the mode of transmission. Here, to establish a base for future progress in better understanding of this infectious disease, we reviewed the characteristics of the disease together with an update of reported cases in Japan., (© 2012 Japanese Dermatological Association.)

The etiology, clinical manifestations, and treatment of 19 sporadic cases of Buruli ulcer (BU) in Japan are described. The cases originated in different regions of Honshu Island, with no evidence of patient contact with an aquatic environment. The majority (73.7%) of cases occurred in females, with an average age of 39.1 years for females and 56.8 years for males. All patients developed ulcers on exposed areas of the skin (e.g., face, extremities). Most ulcers were <5 cm in diameter (category I), except in one severe progressive case (category II). Pain was absent in 10 of the 19 cases. Fourteen ulcers were surgically excised, and nine patients needed skin grafting. All cases were treated with various antibiotic regimens, with no reported recurrences as of March 2011. Mycobacterium ulcerans-specific IS2404 was detected in all cases. Ten isolates had identical 16S rRNA gene sequences, which were similar to those of M. ulcerans. However, the rpoB gene showed a closer resemblance to Mycobacterium marinum or Mycobacterium pseudoshottsii. PCR identified pMUM001 in all isolates but failed to detect one marker. DNA-DNA hybridization misidentified all isolates as M. marinum. The drug susceptibility profile of the isolates also differed from that of M. ulcerans. Sequence analysis revealed "Mycobacterium ulcerans subsp. shinshuense" as the etiologic agent of BU in Japan. Clinical manifestations were comparable to those of M. ulcerans but differed as follows: (i) cases were not concentrated in a particular area; (ii) there was no suspected connection to an aquatic environment; (iii) drug susceptibility was different; and (iv) bacteriological features were different.

Treatment of erythema nodosum leprosum (ENL, type 2 reaction) using thalidomide provides effective alternative choice to steroid therapy. Yet, the Japanese National Health Insurance approves thalidomide prescription only for the treatment of multiple myeloma under the Thalidomide Education and Risk Management System (TERMS). Benefit of thalidomide therapy for patients with ENL is already an established fact based on various reports from other countries, but limited experiences and standards in Japan have hindered application of the medication to our patients. This led us to compose a local guideline. Based on and following the TERMS, we suggest starting thalidomide from 50-100 mg/day and then onwards adjusting the dose according to the symptoms of each patient, not to exceed the maximum recommended dose of 300 mg/day, for the treatment of ENL.

Until the Japanese Leprosy Prevention Law was abolished in 1996, leprosy patients, regardless of their severity, had to be treated by accredited doctors. The majority of them had to be confined in a sanatorium to be treated, since only few hospitals/sanatoria had outpatient clinics for leprosy patients. This de facto confinement limited their occupational, social, financial, and family options, but no clear criteria/guidelines allowing discharge existed. The importance of leprosy outpatient clinics was almost never debated until 1962, when Tofu Association (a foundation established in 1952 to support the confined patients) and the National Suruga Sanatorium planned the opening of the clinic. This clinic looked after total of 4,977 patients until the abolishment of the Law. Since 1996, 349 persons consulted the clinic as of 2010. The importance of the continuation of these clinics is beyond dispute, even in low-endemic countries. However, the diminishing number of patients and demands in this country makes the management difficult. Thus, coordination with the local clinics and dermatologists is inevitable.

The Leprosy Mailing List (LML) is an e-mailing list open to whoever interested in the field from all over the world. It acts as a forum for exchanging information related to Hansen's disease. It was established in February 2001 in Italy, and the present moderator of the LML is Dr. Salvatore Noto. He and his colleague have recently introduced an atlas for diagnosing Hansen's disease which they brought together information and photos collected through the LML. The atlas is divided into three sections, (1) Introduction, (2) Cardinal signs, and (3) Diagnosis and the clinical spectrum of leprosy, and they are all accompanied with relevant photos. This time, Dr. Noto kindly permitted us to translate the atlas into Japanese to be published in the Japanese Journal of Leprosy and posted in the Japanese Leprosy Association homepage. This article includes the translation and some of the most informative photos. For more information, please refer to the homepage where you will find all photos in the atlas.

Ectoparastiosis by Tunga penetrans is becoming more common in non-tropical countries as people travel more to endemic areas. We present here a classic case of imported tungiasis including a history of visit to an endemic region and its typical presentation. Diagnosis with dermoscopy, treatment and prevention are discussed., (© 2010 Japanese Dermatological Association.)