Evolutionary history of Mycobacterium leprae in the Pacific Islands.

As one of the oldest known human diseases, leprosy or Hansen's disease remains a public health concern around the world with over 200 000 new cases in 2018. Most human leprosy cases are caused by Mycobacterium leprae, but a small number of cases are now known to be caused by Mycobacterium lepromatosis, a sister taxon of M. leprae. The global pattern of genomic variation in M. leprae is not well defined. Particularly, in the Pacific Islands, the origins of leprosy are disputed. Historically, it has been argued that leprosy arrived on the islands during nineteenth century colonialism, but some oral traditions and palaeopathological evidence suggest an older introduction. To address this, as well as investigate patterns of pathogen exchange across the Pacific Islands, we extracted DNA from 39 formalin-fixed paraffin-embedded biopsy blocks dating to 1992-2016. Using whole-genome enrichment and next-generation sequencing, we produced nine M. leprae genomes dating to 1998-2015 and ranging from 4-63× depth of coverage. Phylogenetic analyses indicate that these strains belong to basal lineages within the M. leprae phylogeny, specifically falling in branches 0 and 5. The phylogeographical patterning and evolutionary dating analysis of these strains support a pre-modern introduction of M. leprae into the Pacific Islands. This article is part of the theme issue 'Insights into health and disease from ancient biomolecules'.

Damien de Veuster (1840-1889): A life devoted to lepers.

Father Damien de Veuster, or Saint Damien of Molokai (1840-1889), was one of the pioneers of the holistic approach to care provision for leprosy patients and contributed to the overcoming of the patients' social stigmatization. He devoted his life to the lepers living in America's only leper colony, on the Hawaiian island of Molokai, where people with leprosy were required to live under government-sanctioned medical quarantine. Father Damien gained practical skills in caring for the sick, eagerly learning wound cleansing, bandaging techniques, and drug administration from a nurse. Mahatma Gandhi said that Father Damien's work had inspired his own social campaigns in India.

The Exile of Hansen's Disease Patients to Moloka'i: A Diffusion of Innovations Perspective.

This article analyzes the exile of patients with Hansen's disease (leprosy) to Moloka'i (Hawaii) by applying the diffusion of innovations (DoI) theory. Developed by Rogers, DoI posits that an innovation (i.e., idea, movement, or trend) is initiated within a culture. Then, it is diffused via particular channels across diverse cultures. Instead of evolving independently, innovations diffuse from one culture to another through various forms of contact and communication. In the context of this analysis, the objective is to examine how the diffusion of certain ideas, namely, abolishing the stigma associated with leprosy, could have improved the lives of Hawaiians. An important premise of this article is that the Hawaiian government barely applied the tenets of DoI, which is the reason why many people lost their lives. So, this article seeks to explore what could have been done to improve their situation and what pitfalls should be avoided in the future.

A cilevirus infects ornamental hibiscus in Hawaii.

The complete nucleotide sequence of a virus infecting ornamental hibiscus (Hibiscus sp.) in Hawaii with symptoms of green ringspots on senescing leaves was determined from double-stranded RNA isolated from symptomatic tissue. Excluding polyadenylated regions at the 3' termini, the bipartite RNA genome was 8748 and 5019 nt in length for RNA1 and RNA2, respectively. The genome organization was typical of a cilevirus: RNA1 encoded a large replication-associated protein with methyltransferase, protease, helicase and RNA-dependent RNA polymerase domains as well as a 29-kDa protein of unknown function. RNA2 possessed five open reading frames that potentially encoded proteins with molecular masses of 15, 7, 62, 32, and 24 kDa. The 32-kDa protein is homologous to 3A movement proteins of RNA viruses; the other proteins are of unknown function. A proteome comparison revealed that this virus was 92 % identical to citrus leprosis virus cytoplasmic type 2 (CiLV-C2), a recently characterized cilevirus infecting citrus with leprosis-like symptoms in Colombia. The high sequence similarity suggests that the virus described in this study could be a strain of CiLV-C2, but since the new genus Cilevirus does not have species demarcation criteria established at present, the classification of this virus infecting hibiscus is open to interpretation. This study represents the first documented case of a cilevirus established in the United States and provides insight into the diversity within the genus Cilevirus.

Characterization of a virus infecting Citrus volkameriana with citrus leprosis-like symptoms.

A Citrus volkameriana tree displaying symptoms similar to citrus leprosis on its leaves and bark was found in Hawaii. Citrus leprosis virus C (CiLV-C)-specific detection assays, however, were negative for all tissues tested. Short, bacilliform virus-like particles were observed by transmission electron microscopy in the cytoplasm of symptomatic leaves but not in healthy controls. Double-stranded (ds) RNAs ≈8 and 3 kbp in size were present in symptomatic leaf tissue but not in healthy controls. Excluding poly(A) tails, the largest molecule, RNA1, was 8,354 bp in length. The ≈3 kbp dsRNA band was found to be composed of two distinct molecules, RNA2 and RNA3, which were 3,169 and 3,113 bp, respectively. Phylogenetic analyses indicated that the RNA-dependent RNA polymerase (RdRp) domain located in RNA1 was most closely related to the RdRp domain of CiLV-C. A reverse-transcription polymerase chain reaction assay developed for the detection of this virus was used to screen nearby citrus trees as well as Hibiscus arnottianus plants with symptoms of hibiscus green spot, a disease associated with infection by Hibiscus green spot virus (HGSV). All nearby citrus trees tested negative with the assay; however, symptomatic H. arnottianus plants were positive. All three RNAs were present in symptomatic H. arnottianus and were >98% identical to the RNAs isolated from C. volkameriana. We contend that the virus described in this study is HGSV, and propose that it be the type member of a new virus genus, Higrevirus.

Hansen disease among Micronesian and Marshallese persons living in the United States.

An increasing proportion of Hansen disease cases in the United States occurs among migrants from the Micronesian region, where leprosy prevalence is high. We abstracted surveillance and clinical records of the National Hansen's Disease Program to determine geographic, demographic, and clinical patterns. Since 2004, 13% of US cases have occurred in this migrant population. Although Hawaii reported the most cases, reports have increased in the central and southern states. Multibacillary disease in men predominates on the US mainland. Of 49 patients for whom clinical data were available, 37 (75%) had leprosy reaction, neuropathy, or other complications; 17 (37%) of 46 completed treatment. Comparison of data from the US mainland with Hawaii and country-of-origin suggests under-detection of cases in pediatric and female patients and with paucibacillary disease in the United States. Increased case finding and management, and avoidance of leprosy-labeled stigma, is needed for this population.

[Leprosy and medicine II--progress and establishment of an absolute isolation policy].

The leprosy policy of Japan began from when the government enacted "law No. 11 (The leprosy prevention act)" in 1907 (Meiji 40) and several leprosy sanatoriums were built to receive previously homeless patients. Then, with the rise of totalitarianism, the isolation policy of Japan gained national support under the slogan "Patient Relief", which would become a major factor behind the enactment of "Leprosy Prevention Law" in 1931 (Showa 6) by which the leprosy policy was changed to one of absolute isolation aimed at the internment of all leprosy patients. From recent research on the leprosy policy of Japan, the internment of all leprosy patients, isolation for life, social defense, and neglect of patients' human-rights had tragic results in many cases. However, there is little research which can reply clearly to the question of whether the leprosy policy of Japan was really original and what factors led to the formation of the absolute isolation policy. This paper focuses on the relation between leprosy policy and treatment, and from this, I make clear the similarities, or peculiarities, of the isolation policy between Japan and the rest of the world, while clarifying the factors associated with the progress of the absolute isolation policy. The processes involved were historical and medical historical in that the relation between the formation of a national health system and the progress of the isolation policy of Meiji Era, the proposal of the isolation policy by Dr. Keizo Dohi, Dr. Shibasaburo Kitasato, and Dr. Masatsugu Yamane; the practical application of this policy by Dr. Kensuke Mitsuda, and the decision to enact this policy and its support by the Health and Medical Bureau and the Department of the Interior, as well as many other factors, all contributed to the final implementation of the absolute isolation policy.

Hanseniaspora meyeri sp. nov., Hanseniaspora clermontiae sp. nov., Hanseniaspora lachancei sp. nov. and Hanseniaspora opuntiae sp. nov., novel apiculate yeast species.

Fourteen apiculate yeast strains isolated from various sources in South Africa, North America and the Hawaiian islands were found to be genetically divergent from other Hanseniaspora-Kloeckera species by using randomly amplified polymorphic DNA (RAPD)-PCR. After cluster analysis of the RAPD-PCR fingerprints, five groups were recognized. DNA reassociation values among representatives of these groups and strains of Hanseniaspora-Kloeckera species revealed that the strains represent five novel species. Four are described here as novel species of HANSENIASPORA: Hanseniaspora meyeri sp. nov. (type CBS 8734(T)), Hanseniaspora clermontiae sp. nov. (type CBS 8821(T)), Hanseniaspora lachancei sp. nov. (type CBS 8818(T)) and Hanseniaspora opuntiae sp. nov. (type CBS 8733(T)). The fifth novel species, which is represented by only a single strain, CBS 8772, is not introduced as a new taxon. Phylogenetic analyses of the D1/D2 region of the 26S rDNA and internal transcribed spacer (ITS) regions with 5.8S rDNA sequences placed H. meyeri, H. clermontiae, H. lachancei, H. opuntiae and strain CBS 8772 close to Hanseniaspora uvarum and Hanseniaspora guilliermondii. The key characteristics for standard physiological identification of H. clermontiae and H. lachancei were respectively maximal growth temperature and assimilation of 2-keto-D-gluconate. However, physiological characteristics did not allow the distinction of H. opuntiae and strain CBS 8772 from H. guilliermondii or H. meyeri from H. uvarum. These three novel taxa can be identified by either ITS sequencing or PCR-RFLP of ITS regions using restriction enzymes MboII and HinfI.

[Doctor Eyvind Kraft--halfway around the world in the 1880s]. / Lege Eyvind Kraft--jorden halvveis rundt i 1880-årene.

More than every second Norwegian 19th century physician made one or more study trips abroad. Some of them were probably more inspired by love of adventure than by the prospect of gaining new medical insight. This was probably also true of my great-grandfather, Eyvind Kraft. Shortly after completing medical school in 1879, he left Norway on the "Musca", an emigrant vessel, bound for Hawaii. He returned home approximately six years later to establish a sanatorium. In the meantime he worked as a ship's doctor, made a contribution to the understanding of the contagiousness of leprosy, and was among the founding members of the first medical society in the state of Wisconsin. Back in Norway he worked at the sanatorium, but also as a general practitioner and among fishermen during the seasonal fisheries. He had to travel to the Continent in an attempt to cure his "nerve disease". Eyvind Kraft's life tells an exciting story of exotic places and of the view of disease in his time.

Cluster of leprosy cases in Kona, Hawaii; impact of the Compact of Free Association.

International travel and migration will continue to contribute to the changing patterns of Hansen's disease (HD) in the United States. The majority of cases will be immigrants and refugees entering the country from leprosy-endemic regions. The Compact of Free Association, through its provision of free travel between the Freely Associated States and the United States without need for health screening, has created new public health issues. This cluster of HD cases in Kona, Hawaii, U.S.A., highlights the difficulties in detecting and monitoring the spread of disease in immigrant populations. This is a growing problem only likely to worsen in the coming years. In groups with cultural, language or other socioeconomic barriers, special and creative methods may be needed to tackle the problems of detection, treatment and education. Clinicians must remain mindful of the diagnosis of HD in high-risk groups.

Cluster of leprosy cases in Kona, Hawaii; impact of the compact of free association

International travel and migration will continue to contribute to the changing patterns of Hansen's disease (HD) in the United States. The majority of cases will be immigrants and refugees entering the country from leprosy-endemic regions. The Compact of Free Association, through its provision of free travel between the Freely Associated States and the United States without need for health screening, has created new public health issues. This cluster of HD cases in Kona, Hawaii, U.S.A., highlights the difficulties in detecting and monitoring the spread of disease in immigrant populations. This is a growing problem only likely to worsen in the coming years. In groups with cultural, language or other socioeconomic barriers, special and creative methods may be needed to tackle the problems of detection, treatment and education. Clinicians must remain mindful of the diagnosis of HD in high-risk groups.

Herbal medicines in Hawaii from tradition to convention.

The stories of kava and chaulmoogra demonstrate the importance of herbal products in ancient and recent Hawaiian medicine. Kava is a psychoactive beverage that has been used ceremonially for millennia throughout the Pacific. It is a nonfermented depressant that causes tranquil intoxication in which thoughts and memory remain clear. Its broad pharmacologic activity led to use in Hawaii to treat skin disorders and later in Germany to treat gonorrhea. Kava is now available outside the Pacific basin as a relaxant, emerging as a popular, albeit deritualized, natural product. In the late 19th century, the main treatment for leprosy was chaulmoogra, extracted from Hydnocarpus seeds. Chaulmoogra had been a traditional treatment for skin diseases in Ayurvedic and Chinese medicine. Chaulmoogra from Asian markets was expensive and usually adulterated so the USDA decided to plant Hydnocarpus in Hawaii. Joseph Rock, a botanist at University of Hawaii, trekked through southeast Asia collecting fresh seeds to plant on Oahu. Rock's trees provided chaulmoogra for leprosy patients on Molokai and elsewhere until it was replaced by dapsone. Chaulmoogra, once the treatment for leprosy worldwide, is now nearly forgotten; kava, once poorly known outside the Pacific, is now a widely-used alternative medicine. Hawaii will probably continue its role in the transition of plants from traditional use to conventional use.