Spatial-temporal trends in leprosy burden and its associations with socioeconomic and physical geographic factors: results from the Global Burden of Disease Study 2019.

OBJECTIVES: The purpose of our study was to assess the multiscalar changes in leprosy burden and its associated risk factors over the last three decades. STUDY DESIGN: We conducted an in-depth examination of leprosy's spatial-temporal trends at multiple geographical scale (global, regional, and national), utilizing information from Global Burden of Disease, Injuries, and Risk Factors Study (GBD 2019). METHODS: Incidence and the estimated annual percentage change (EAPC) in age-standardized incidence rate (ASIR) of leprosy were determined, with countries categorized based on leprosy incidence changes. We examined socioeconomic and physical geography influences on leprosy incidence via Spearman correlation analysis, using ternary phase diagrams to reveal the synergetic effects on leprosy occurrence. RESULTS: Globally, incident cases of leprosy decreased by 27.86% from 1990 to 2019, with a reduction in ASIR (EAPC = -2.53), yet trends were not homogeneous across regions. ASIR and EAPC correlated positively with sociodemographic index (SDI), and an ASIR growth appeared in high SDI region (EAPC = 3.07). Leprosy burden was chiefly distributed in Tropical Latin America, Oceania, Central Sub-Saharan Africa, and South Asia. Negative correlations were detected between the incidence of leprosy and factors of SDI, GDP per capita, urban population to total population, and precipitation, whereas the number of refugee population, temperature, and elevation showed opposite positive results. CONCLUSIONS: Despite a global decline in leprosy over the past three decades, the disparities of disease occurrence at regional and national scales still persisted. Socioeconomic and physical geographic factors posed an obvious influence on the transmission risk of leprosy. The persistence and regional fluctuations of leprosy incidence necessitate the ongoing dynamic and multilayered control strategies worldwide in combating this ancient disease.

Epidemiological, clinical, and geographical characterization of Leprosy in the County of Santarém-Pará: Insights for effective control and targeted intervention.

Leprosy is an infectious disease characterized by slow and chronic evolution, caused by Mycobacterium leprae and or Mycobacterium lepromatosis, an intracellular alcohol-acid-resistant (BAAR) bacillus. The objective of this study was to provide an epidemiological, clinical, and geographic characterization of leprosy in the city of Santarém-Pará during the period 2011-2020. A cross-sectional, descriptive, and quantitative approach was used, employing maps and tables to illustrate clinical and epidemiological variables, including: sex, age, race, area of residence, operational classification, clinical form, number of skin lesions, number of affected nerves, and health units. During the analyzed period, 581 cases of leprosy were diagnosed, resulting in the following cumulative incidence rates: male (60%); age over 15 years (94%); urban area (73%); multibacillary (74%); borderline form (46%); skin lesions greater than 5 (34%); and no nerves affected (68%). In the urban perimeter, a higher cumulative incidence of cases was observed in the central area with 133 cases. However, the health unit reporting the largest number of cases belonged to the southern area, specifically the Basic Health Unit of Nova República, with 48 cases. This study highlights the need to characterize the nuances of leprosy and its variability within the urban environment, according to different areas. Further research is essential to inform the implementation of public policies aimed at addressing the population with the highest vulnerability index, thereby reducing leprosy rates in Santarém.

Autochthonous leprosy in Spain: Has the transmission of Mycobacterium leprae stopped?

BACKGROUND: The aim of this study is to explore whether transmission of M. leprae has ceased in Spain, based upon the patterns and trends of notified cases. METHODOLOGY: Data on new cases reported to the National Leprosy Registry between the years 2003-2018 were extracted. In absence of detailed travel history, cases were considered "autochthonous" or "imported" based on whether they were born within or outside of Spain. These data were analyzed by age, sex, clinical type, country of origin, and location of residence at time of notification. PRINCIPAL FINDINGS: Data were available on 61 autochthonous and 199 imported cases since 2003. There were clear declines in incidence in both groups, and more imported than autochthonous cases every year since 2006. Autochthonous cases were more frequently multibacillary and had older age at diagnosis compared to imported cases. All the autochthonous cases had been born before 1985 and were more than 25 years old at diagnosis. Male-to-female ratio increased with time for autochthonous cases (except for the last time period). The imported cases originated from 25 countries, half of them from Brasil and Paraguay. Autochthonous cases were mainly distributed in the traditionally endemic regions, especially Andalucía and the eastern Mediterranean coast. CONCLUSIONS: Autochthonous and imported cases have different epidemiologic patterns in Spain. There was a clear decline in incidence rates of autochthonous disease, and patterns consistent with those reported from other regions where transmission has ceased. Autochthonous transmission of M. leprae is likely to have now effectively stopped in Spain.

Genotyping of Mycobacterium leprae for understanding the distribution and transmission of leprosy in endemic provinces of China.

OBJECTIVES: Understanding the nature of Mycobacterium leprae transmission is vital to implement better control strategies for leprosy elimination. The present study expands the knowledge of county-level strain diversity, distribution, and transmission patterns of leprosy in endemic provinces of China. METHODS: We genetically characterized 290 clinical isolates of M. leprae from four endemic provinces using variable number tandem repeats (VNTR) and single nucleotide polymorphisms (SNPs). Attained genetic profiles and cluster consequences were contrasted with geographical and migration features of leprosy at county levels. RESULTS: Considering the allelic variability of 17 VNTR loci by the discriminatory index, (GTA)9, (AT)17, (AT)15, (TA)18, (TTC)21, and (TA)10 are reported to be more highly polymorphic than other loci. The VNTR profile generated the low-density clustering pattern in the counties of Sichuan and Yunnan, whereas clusters have been observed from the isolates from Huayuan (N = 6), Yongding (N = 3), Zixing (N = 3), Chenxi (N = 2) and Zhongfang (N = 2) counties of Hunan, and Zhijin (N = 3), Anlong (N = 2), Zhenning (N = 2), and Xixiu (N = 2) counties of Guizhou. In some clusters, people's social relations have been observed between villages. From the 290 clinical isolates, the most predominantly reported SNP was 3K (278, 95.8%), followed by SNP 1D (10, 3.4%), which are typically observed to be predominant in China. We also detected the novel SNP 3J (2, 0.8%), which has not yet been reported in China. CONCLUSION: The clustering pattern of M. leprae indicates the transmission of leprosy still persists at county levels, suggesting that there is a need to implement better approaches for tracing the close contacts of leprosy patients.

Yeast communities of secondary peat swamp forests in Thailand and their antagonistic activities against fungal pathogens cause of plant and postharvest fruit diseases.

Secondary peat swamp forest (PSF) arise by degradation of primary PSF as a result of fire and human activities. Yeasts diversity of Kuan Kreng (KK) and Rayong Botanical Garden (RBG) PSF, which are two secondary PSF in southern and in eastern Thailand, respectively, were investigated. Yeasts were isolated from soil and peat soil by the dilution plate and enrichment techniques. From six samples collected from KK PSF, 35 strains were obtained, and they were identified based on the sequence analysis of the D1/D2 region of the large subunit (LSU) rRNA gene 13 species in 12 genera, and one potential new species of the genus Galactomyces were detected. Thirty-two strains were obtained from six samples collected from RBG PSF and 26 strains were identified as 13 known yeast species in 11 genera, whereas six strains were found to represent two potential new species of the genera Papiliotrema and Moesziomyces. Among yeast strains isolated from KK PSF, the number of strains in the phylum Ascomycota and Basidiomycota were equal, whereas there were slightly fewer strains in Ascomycota than in Basidiomycota among the strains obtained from RBG PSF. The yeast strains were evaluated for their antagonistic activities against fungal pathogens which cause rice diseases (Fusarium moniliforme, Helminthosporium oryzae, Rhizoctonia solani, Curvularia lunata and Pyricularia grisea) and postharvest disease of fruits (Phytophthora palmivora, Lasiodiplodia theobromae and Colletotrichum gloeosporioides). Twelve strains of seven species were found to be antagonistic yeast strains. Starmerella kuoi DMKU-SPS13-6, Hanseniaspora lindneri DMKU ESS10-9 and Piskurozyma taiwanensis DMKU-SPS12-2 capable to inhibit R. solani by 70.1-76.2%, Wickerhamomyces anomalus DMKU SPS6-1 and three Rhodotorula taiwanensis strains (DMKU SPS8-1, DMKU ESS9-3, DMKU SPS9-2) inhibited C. lunata by 69.8-71.9%, Hanseniaspora lindneri DMKU ESS10-9 and Scheffersomyces spartinae DMKU SPS9-3 inhibited P. grisea by 81.9-84.4% and four Papiliotrema laurentii strains (DMKU-SPS15-1, DMKU-ESS11-2, DMKU-ESS8-2, DMKU-ESS6-4) inhibited P. palmivora by 53.2-59.5%.

Trend of leprosy detection rate in Brazil, 1990 to 2016.

The objective of this study was to describe the trend of detection of the disease in Brazil from 1990 to 2016. The joinpoint regression model was used. There was a significant trend of decreased detection in the country (average annual percent change -1.8%) and in the South (average annual percent change=-3.5%) and Southeast regions (average annual percent change=-4.5%). The Northeast (average annual percent change=0.2%), the Central-West (average annual percent change=-1.5%), and the North (average annual percent change=-2.6%) showed a stationary trend (p>0.05). Eleven states showed a decreasing trend. Alagoas (average annual percent change=2.1%) and Rio Grande do Norte (average annual percent change=1.4%) presented significant increase (p<0.001). The heterogeneous pattern of trend between regions and states shows that efforts are needed to eliminate the disease.

Trend of leprosy detection rate in Brazil, 1990 to 2016

Abstract The objective of this study was to describe the trend of detection of the disease in Brazil from 1990 to 2016. The joinpoint regression model was used. There was a significant trend of decreased detection in the country (average annual percent change −1.8%) and in the South (average annual percent change = −3.5%) and Southeast regions (average annual percent change = −4.5%). The Northeast (average annual percent change = 0.2%), the Central-West (average annual percent change = −1.5%), and the North (average annual percent change = −2.6%) showed a stationary trend (p > 0.05). Eleven states showed a decreasing trend. Alagoas (average annual percent change = 2.1%) and Rio Grande do Norte (average annual percent change = 1.4%) presented significant increase (p < 0.001). The heterogeneous pattern of trend between regions and states shows that efforts are needed to eliminate the disease.

Geographic and socioeconomic factors associated with leprosy treatment default: An analysis from the 100 Million Brazilian Cohort.

BACKGROUND: Although leprosy is largely curable with multidrug therapy, incomplete treatment limits therapeutic effectiveness and is an important obstacle to disease control. To inform efforts to improve treatment completion rates, we aimed to identify the geographic and socioeconomic factors associated with leprosy treatment default in Brazil. METHODOLOGY/PRINCIPAL FINDINGS: Using individual participant data collected in the Brazilian national registries for social programs and notifiable diseases and linked as part of the 100 Million Brazilian Cohort, we evaluated the odds of treatment default among 20,063 leprosy cases diagnosed and followed up between 2007 and 2014. We investigated geographic and socioeconomic risk factors using a multivariate hierarchical analysis and carried out additional stratified analyses by leprosy subtype and geographic region. Over the duration of follow-up, 1,011 (5.0%) leprosy cases were observed to default from treatment. Treatment default was markedly increased among leprosy cases residing in the North (OR = 1.57; 95%CI 1.25-1.97) and Northeast (OR = 1.44; 95%CI 1.17-1.78) regions of Brazil. The odds of default were also higher among cases with black ethnicity (OR = 1.29; 95%CI 1.01-1.69), no income (OR = 1.41; 95%CI 1.07-1.86), familial income ≤ 0.25 times Brazilian minimum wage (OR = 1.42; 95%CI 1.13-1.77), informal home lighting/no electricity supply (OR = 1.53; 95%CI 1.28-1.82), and household density of > 1 individual per room (OR = 1.35; 95%CI 1.10-1.66). CONCLUSIONS: The findings of the study indicate that the frequency of leprosy treatment default varies regionally in Brazil and provide new evidence that adverse socioeconomic conditions may represent important barriers to leprosy treatment completion. These findings suggest that interventions to address socioeconomic deprivation, along with continued efforts to improve access to care, have the potential to improve leprosy treatment outcomes and disease control.

Trend analysis of leprosy indicators in a hyperendemic Brazilian state, 2001-2015.

OBJECTIVE: To analyze the temporal trend of leprosy indicators in a hyperendemic state of Brazil, from 2001-2015. METHODS: This is a time-series study of leprosy indicators in the state of Maranhão, Northeastern region of Brazil. The study used data from the Brazilian National System of Reportable Diseases, for the period between 2001 and 2015. The following indicators were evaluated: (i) detection coefficient in the general population; (ii) detection coefficient in people under 15 years old; (iii) rate of cases with grade 2 physical disability in the diagnosis; (iv) rate of examined contacts, and (v) proportion of healing . The Prais-Winsten regression model was used for trend analysis. Analyses were performed for the state and by each health region. RESULTS: 77,697 leprosy cases were analyzed in the general population and 7,599 in individuals under 15 years old. The detection coefficient in the general population ranged from 80.7/100 thousand inhabitants in 2001 to 51.2/100 thousand inhabitants in 2015. The coefficient in the general population presented a downward trend (annual percentage variation [APV] = -2.98; 95%CI -4.15- -1.79). For the population under 15 years old, the rate was 24.9/100 thousand inhabitants in 2001, and 19.9/100 thousand inhabitants in 2015, with downward trend (APV = -3.07; 95%CI -4.95- -1.15). It was observed upward trend in rate of contacts examined (APV = 2.35; 95%CI 0.58-4.15) and rate of cases with grade 2 disability (APV = 2.19; 95%CI 0.23-4.19). Stationary trend was observed in the proportion of healing (APV = -0.10; 95%CI -0.50-0.30). Regional differences were found in the performance of the indicators. CONCLUSIONS: A downward trend for the detection coefficients in the general population and in individuals under 15 years old was found in Maranhão. Despite this result, the rates are still very high, demanding efforts from all spheres of public administration and health professionals to reduce the burden of the disease in the state.

Trend analysis of leprosy indicators in a hyperendemic Brazilian state, 2001-2015 / Análise da tendência dos indicadores da hanseníase em estado brasileiro hiperendêmico, 2001-2015

ABSTRACT OBJECTIVE To analyze the temporal trend of leprosy indicators in a hyperendemic state of Brazil, from 2001-2015. METHODS This is a time-series study of leprosy indicators in the state of Maranhão, Northeastern region of Brazil. The study used data from the Brazilian National System of Reportable Diseases, for the period between 2001 and 2015. The following indicators were evaluated: (i) detection coefficient in the general population; (ii) detection coefficient in people under 15 years old; (iii) rate of cases with grade 2 physical disability in the diagnosis; (iv) rate of examined contacts, and (v) proportion of healing . The Prais-Winsten regression model was used for trend analysis. Analyses were performed for the state and by each health region. RESULTS 77,697 leprosy cases were analyzed in the general population and 7,599 in individuals under 15 years old. The detection coefficient in the general population ranged from 80.7/100 thousand inhabitants in 2001 to 51.2/100 thousand inhabitants in 2015. The coefficient in the general population presented a downward trend (annual percentage variation [APV] = -2.98; 95%CI -4.15- -1.79). For the population under 15 years old, the rate was 24.9/100 thousand inhabitants in 2001, and 19.9/100 thousand inhabitants in 2015, with downward trend (APV = -3.07; 95%CI -4.95- -1.15). It was observed upward trend in rate of contacts examined (APV = 2.35; 95%CI 0.58-4.15) and rate of cases with grade 2 disability (APV = 2.19; 95%CI 0.23-4.19). Stationary trend was observed in the proportion of healing (APV = -0.10; 95%CI -0.50-0.30). Regional differences were found in the performance of the indicators. CONCLUSIONS A downward trend for the detection coefficients in the general population and in individuals under 15 years old was found in Maranhão. Despite this result, the rates are still very high, demanding efforts from all spheres of public administration and health professionals to reduce the burden of the disease in the state.

RESUMO OBJETIVO Analisar a tendência temporal dos indicadores da hanseníase em estado brasileiro hiperendêmico, no período de 2011 a 2015. MÉTODOS Trata-se de um estudo de série temporal dos indicadores de hanseníase no estado do Maranhão, região Nordeste, que utilizou dados do Sistema Nacional de Agravos de Notificação, no período de 2001 a 2015. Foram avaliados os seguintes indicadores: (i) coeficiente de detecção na população em geral; (ii) coeficiente de detecção em menores de 15 anos; (iii) proporção de casos com grau 2 de incapacidade física no diagnóstico; (iv) proporção de contatos examinados e (v) proporção de cura. Para análise da tendência foi utilizado o modelo de regressão de Prais Winsten . As análises foram realizadas para o Estado e por região de saúde. RESULTADOS Foram analisados 77.697 casos de hanseníase na população geral e 7.599 em menores de 15 anos. O coeficiente de detecção na população geral variou de 80,7/100 mil habitantes em 2001 para 51,2/100 mil habitantes em 2015. Verificou-se tendência decrescente do coeficiente na população geral (variação percentual anual [VPA] = -2,98; IC95% -4,15- -1,79). Na população menor de 15 anos, o coeficiente foi de 24,9/100 mil habitantes em 2001 para 19,9/100 mil habitantes em 2015, com tendência decrescente (VPA = -3,07; IC95% -4,95- -1,15). Observou-se tendência crescente na proporção de contatos examinados (VPA = 2,35; IC95%: 0,58-4,15) e na proporção de casos com grau 2 de incapacidade (VPA = 2,19; IC95% 0,23-4,19). Verificou-se tendência estacionária na proporção de cura de hanseníase (VPA = -0,10; IC95% -0,50-0,30). Observaram-se diferenças regionais no desempenho dos indicadores. CONCLUSÕES A tendência dos coeficientes de detecção na população geral e em menores de 15 anos mostrou-se decrescente no Maranhão. Apesar disso, as taxas ainda são muito elevadas, o que exige esforços de todas as esferas de gestão e profissionais da saúde para redução da carga da doença no estado.

Monitoring and detection of leprosy patients in Southwest China: A retrospective study, 2010-2014.

More than 100 counties, mainly in southwest China, report incidence rates of leprosy >1/100,000. The current study analysed the epidemiology of leprosy in southwest China to improve our understanding of the transmission pattern and improve control programs. 207 counties were selected in southwest China. Leprosy patients and their household contacts were recruited. The data from the medical interview and the serological antileprosy antibody of the leprosy patients were analysed. A total of 2,353 new cases of leprosy were interviewed. The distribution of leprosy patients was partly associated with local natural and economic conditions, especially several pocket areas. A total of 53 from 6643 household contacts developed leprosy, and the incidence rate of leprosy in the household contacts was 364/100,000 person-years. We found that NDO-BSA attained higher positive rates than MMP-II and LID-1 regardless of clinical types, disability and infection time in leprosy patients. By means of combination of antigens, 88.4% patients of multibacillary leprosy were detected, in contrast to 59.9% in paucibacillary leprosy. Household contacts should be given close attention for the early diagnosis, disruption of disease transmission and precise control. Applications of serology for multi-antigens were recommended for effective coverage and monitoring in leprosy control.

Genotyping of Mycobacterium leprae for better understanding of leprosy transmission in Fortaleza, Northeastern Brazil.

Leprosy is endemic in large part of Brazil with 28,761 new patients in 2015, the second largest number worldwide and reaches 9/10.000 in highly endemic regions and 2.7/10.000 in the city of Fortaleza, Ceará, Northeast Brazil. For better understanding of risk factors for leprosy transmission, we conducted an epidemiologic study supplemented by 17 locus VNTR and SNP 1-4 typing of Mycobacterium leprae in skin biopsy samples from new multibacillary (MB) patients diagnosed at a reference center in 2009 and 2010. Among the 1,519 new patients detected during the study period, 998 (65.7%) were MB and we performed DNA extraction and genotyping on 160 skin biopsy samples, resulting in 159 (16%) good multilocus VNTR types. Thirty-eight of these patients also provided VNTR types from M. leprae in nasal swabs. The SNP-Type was obtained for 157 patients and 87% were of type 4. Upon consideration all VNTR markers, 156 different genotypes and three pairs with identical genotypes were observed; no epidemiologic relation could be observed between individuals in these pairs. Considerable variability in differentiating index (DI) was observed between the different markers and the four with highest DI [(AT)15, (TA)18, (AT)17 and (GAA)21] frequently demonstrated differences in copy number when comparing genotypes from both type of samples. Excluding these markers from analysis resulted in 83 genotypes, 20 of which included 96 of the patients (60.3%). These clusters were composed of two (n = 8), three (n = 6), four (n = 1), five (n = 2), six (n = 1), 19 (n = 1) and 23 (n = 23) individuals and suggests that recent transmission is contributing to the maintenance of leprosy in Fortaleza. When comparing epidemiological and clinical variables among patients within clustered or with unique M. leprae genotypes, a positive bacterial index in skin biopsies and knowledge of working with someone with the disease were significantly associated with clustering. A tendency to belong to a cluster was observed with later notification of disease (mean value of 3.4 months) and having disability grade 2. A tendency for lack of clustering was observed for patients who reported to have lived with another leprosy case but this might be due to lack of inclusion of household contacts in the study. Although clusters were spread over the city, kernel analysis revealed that some of the patients belonging to the two major clusters were spatially related to some neighborhoods that report poverty and high disease incidence in children. Finally, inclusion of genotypes from nasal swabs might be warranted. A major limitation of the study is that sample size of 160 patients from a two year period represents only 15% of the new patients and this could have weakened statistical outcomes. This is the first molecular epidemiology study of leprosy in Brazil and although the high clustering level suggests that recent transmission is the major cause of disease in Fortaleza; the existence of two large clusters needs further investigation.

Insight into the evolution and origin of leprosy bacilli from the genome sequence of Mycobacterium lepromatosis.

Mycobacterium lepromatosis is an uncultured human pathogen associated with diffuse lepromatous leprosy and a reactional state known as Lucio's phenomenon. By using deep sequencing with and without DNA enrichment, we obtained the near-complete genome sequence of M. lepromatosis present in a skin biopsy from a Mexican patient, and compared it with that of Mycobacterium leprae, which has undergone extensive reductive evolution. The genomes display extensive synteny and are similar in size (∼3.27 Mb). Protein-coding genes share 93% nucleotide sequence identity, whereas pseudogenes are only 82% identical. The events that led to pseudogenization of 50% of the genome likely occurred before divergence from their most recent common ancestor (MRCA), and both M. lepromatosis and M. leprae have since accumulated new pseudogenes or acquired specific deletions. Functional comparisons suggest that M. lepromatosis has lost several enzymes required for amino acid synthesis whereas M. leprae has a defective heme pathway. M. lepromatosis has retained all functions required to infect the Schwann cells of the peripheral nervous system and therefore may also be neuropathogenic. A phylogeographic survey of 227 leprosy biopsies by differential PCR revealed that 221 contained M. leprae whereas only six, all from Mexico, harbored M. lepromatosis. Phylogenetic comparisons indicate that M. lepromatosis is closer than M. leprae to the MRCA, and a Bayesian dating analysis suggests that they diverged from their MRCA approximately 13.9 Mya. Thus, despite their ancient separation, the two leprosy bacilli are remarkably conserved and still cause similar pathologic conditions.

Geographical heterogeneity in the analysis of factors associated with leprosy in an endemic area of Brazil: are we eliminating the disease?

BACKGROUND: The leprosy transmission chain is very complex and, in order to intervene in this transmission, more must be known about the factors linked to falling ill. There are doubts as to the influence of population size, population density and the disease's magnitude in detection rate trends. This paper aimed to identify factors associated with detection of leprosy in an endemic municipality of Rio de Janeiro State, Brazil. METHODS: This ecological study in Duque de Caxias municipality, Rio de Janeiro State, Brazil, used neighbourhoods (bairros) as the unit of analysis. Selecting new cases of leprosy detected from 1998 to 2006, the analysis examined clinical, socioeconomic and service variables using a Poisson log-Normal model. RESULTS: In the municipality overall, 2572 new cases were detected, a rate of 3.70 cases/10,000 inhabitants. The results describe a heterogeneous distribution of cases and rates in the municipality. The final model displayed a significant association with indeterminate clinical form (ß = 2.599), proportion of homes with running water (ß = -2.334) and presence of a decentralised health care unit (ß = 0.524). CONCLUSION: Although the results indicate progress towards elimination of the disease in the municipality, high rates continue to be detected in municipal sub-regions. The following question can thus be posed: over how wide a geographical area could the disease be thoroughly eliminated, given this heterogeneity within a small municipality?

Debating diseases in Nineteenth-Century Colombia: causes, interests, and the Pasteurian therapeutics

This article explores the medical conceptualization of the causes of diseases in nineteenth-century Colombia. It traces the history of some of the pathologies that were of major concern among nineteenth-century doctors: periodic fevers (yellow fever and malaria), continuous fevers (typhoid fever), and leprosy (Greek elephantiasis). By comparing the transforming conceptualizations of these diseases, this article shows that their changing pattern, the idea of climatic determinism of diseases (neo-Hippocratism and medical geography), the weak standind of the medical community in Colombian society, as well as Pasteurian germ practices were all crucial in the uneven and varied reshaping of their understanding. (AU)

Saccharomyces eubayanus and Saccharomyces uvarum associated with the fermentation of Araucaria araucana seeds in Patagonia.

Mudai is a traditional fermented beverage, made from the seeds of the Araucaria araucana tree by Mapuche communities. The main goal of the present study was to identify and characterize the yeast microbiota responsible of Mudai fermentation as well as from A. araucana seeds and bark from different locations in Northern Patagonia. Only Hanseniaspora uvarum and a commercial bakery strain of Saccharomyces cerevisiae were isolated from Mudai and all Saccharomyces isolates recovered from A. araucana seed and bark samples belonged to the cryotolerant species Saccharomyces eubayanus and Saccharomyces uvarum. These two species were already reported in Nothofagus trees from Patagonia; however, this is the first time that they were isolated from A. araucana, which extends their ecological distribution. The presence of these species in A. araucana seeds and bark samples, led us to postulate a potential role for them as the original yeasts responsible for the elaboration of Mudai before the introduction of commercial S. cerevisiae cultures. The molecular and genetic characterization of the S. uvarum and S. eubayanus isolates and their comparison with European S. uvarum strains and S. eubayanus hybrids (S. bayanus and S. pastorianus), allowed their ecology and evolution us to be examined.

Country profile: leprosy in Brazil.

Brazil has high rates of leprosy case detection, especially in the northern and west-central areas of the country. Effective decentralisation of routine treatment for leprosy has gathered pace since the year 2000 and this has improved access for patients, leading to a peak in new case detection in 2003 and a gradual decline thereafter. This is in parallel with specific government programmes aimed at poverty reduction. Disability prevention and surveillance for drug resistance remain important tasks within the leprosy control programme, in which six key referral centres lead the way.

Neurological disability in leprosy: incidence and gender association in Sergipe, Brazil.

The environmental impact assessment process is over 40 years old and has dramatically expanded. Topics, such as social, health and human rights impact are now included. The main body of an impact analysis is generally hundreds of pages long and supported by countless technical appendices. For large, oil/gas, mining and water resources projects both the volume and technical sophistication of the reports has far exceeded the processing ability of host communities. Instead of informing and empowering, the reports are abstruse and overwhelming. Reinvention is required. The development of a visual integrated impact assessment strategy that utilizes remote sensing and spatial analyses is described.

Leprosy epidemics during history increased protective allele frequency of PARK2/PACRG genes in the population of the Mljet Island, Croatia.

INTRODUCTION: Two regulatory polymorphisms (rs1040079 and rs9356058) shared by PARK2 and PACRG genes were identified as major risk variants for leprosy susceptibility. The aim of this study was to investigate if allele frequencies of these polymorphisms in the isolated population of the island of Mljet, which served as a quarantine for leprosy patients during past centuries, were different to allele frequencies in two control populations with no history of leprosy. SUBJECTS AND METHODS: This study included 88 unrelated Caucasian individuals from the island of Mljet while two control groups included 93 individuals from the island of Rab and 160 individuals from the region of Split. Genotyping for rs1040079 and rs9356058 was performed by "real-time" PCR analysis. We also compared the allele frequency of the rs9356058 polymorphism from the population of Mljet with allele frequencies derived from the existing genome wide association scans in two additional island populations, Vis (924 subjects) and Korcula (909 subjects). RESULTS: We found a significant increase in the frequency of rs9356058 allele C in the population of Mljet when compared to both control groups. We also observed a significant increase in the frequency of rs1040079 allele A in the population of Mljet when compared with the population of Rab, however this increase was not significant when compared with the population of Split. Allele frequencies of both examined polymorphisms did not differ between the two control populations. Protective haplotype rs9356058-rs1040079 CA was also more frequent in the population of Mljet compared with the Rab and Split populations. In addition, an increase of frequency of rs9356058 allele C was also observed in the population of Mljet when compared with the frequency in the Korcula population. CONCLUSION: The results of our study show the association of polymorphisms rs9356058 and rs1040079 in gene PARK2/PACRG with leprosy. The results of our study indicate that exposure to leprosy and mortality in the population caused by leprosy on Mljet resulted in the selection of rs9356058 "protective" C allele in the PARK2 gene, while this was not observed in the two control groups. This is the first study to assess the genetic susceptibility to leprosy in a European population.