Presenting symptoms of leprosy at diagnosis: Clinical evidence from a cross-sectional, population-based study.

BACKGROUND: Leprosy is associated with different dermatologic and neurologic manifestations within a wide clinical spectrum, causing a great diagnostic challenge. Therefore, we aimed to examine associations between common presenting symptoms of leprosy and stage at diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: In this cross-sectional study, we analyzed population-level data from the Leprosy Management Information System (LEPMIS) in Yunnan, China, from 2010-2020 and enrolled patients with newly detected leprosy. The data of 2125 newly detected leprosy patients, with 5000 symptoms, were analyzed. Numbness (828/5000, 16.56%), erythema (802/5000, 16.04%), Painless nor pruritic skin lesions (651/5000, 13.02%), eyebrow hair loss (467/5000, 9.34%), and tubercles (442/5000, 8.84%) were common symptoms of leprosy. The symptoms related to skin (1935/2533, 76.39%) and leprosy reaction (279/297, 93.94%) were mainly existed in MB group. While the symptoms related to disability (263/316, 83.49%), clinical feature (38/56, 69.09%), and facial features (19/23, 82.61%) were predominantly presented in delayed diagnostic group. Despite low proportions, formic sensation (99/5000, 1.98%), pain (92/5000, 1.84%), pruritus (56/5000, 1.12%), finger contracture (109/5000, 2.18%), muscle atrophy (71/5000, 1.42%), and motor dysfunction (18/5000, 0.36%) were reported during the diagnosis of leprosy. The proportions of skin, skin and nerve, and nerve symptoms as initial symptoms were 33.25%, 44.95%, and 21.80% and as only symptoms were 28.66%, 57.81%, and 13.91%, respectively. In those with physical disability, nerve symptoms were the most frequent symptoms (57.65% and 65.36% for the initial and only symptoms, respectively) compared with skin and skin and nerve symptoms. In the delayed diagnosis group, nerve symptoms were the most frequent symptoms (15.73% and 17.25%) and were associated with the longest diagnostic intervals (mean±SD: 38.88±46.02 and 40.35±49.36 months for initial and only symptoms, respectively) when compared with skin and skin and nerve symptoms. CONCLUSIONS: Understanding the nature of presenting symptoms and developing symptom awareness campaigns would improve the level of leprosy awareness in the community. As nerve symptoms were related to a higher proportion of physical disability and longer diagnosis interval, we should increase awareness about nerve symptoms. Individuals with nerve symptoms should be considered the target group. Neurology outpatient visits may provide potential screening opportunities, and holding focused training for specialized neurology medical staff would enhance the capacity of the health system to recognize leprosy early.

Risk factors for physical disability in patients with leprosy disease in Yunnan, China: Evidence from a retrospective observational study.

BACKGROUND: Leprosy is potentially debilitating. The risk factors related to physical disabilities associated with leprosy disease in Yunnan, China was not clear. METHODOLOGY/PRINCIPAL FINDINGS: We studied 10644 newly detected leprosy patients from Yunnan, China, from 1990 to 2019. Factors associated with Grade 1 (G1D) and Grade 2 (G2D) physical disabilities or overall physical disabilities (combined G1D and G2D) associated with leprosy were analyzed using multinomial and ordinal logistic regression analyses. The following factors were associated with the development of physical disability in these patients with leprosy: delayed diagnosis [odds ratio (OR): 5.652, 4.399, and 2.275; 95% confidence intervals (CIs): 4.516-7.073, 3.714-5.212, and 2.063-2.509; for ≥ 10, 5-10 y, and 2-5 years, respectively], nerve damage (OR: 3.474 and 2.428; 95% CI: 2.843-4.244, and 1.959-3.008; for 2 and 1 damaged nerves, respectively), WHO classification of PB (OR: 1.759; 95% CI: 1.341-2.307), Ridley-Jopling classification (OR: 1.479, 1.438, 1.522 and 1.239; 95% CI: 1.052-2.079, 1.075-1.923, 1.261-1.838, and 1.072-1.431; for TT, BT, BB, and BL when compared with LL, respectively), advanced age (OR: 1.472 and 2.053; 95% CI: 1.106-1.960 and 1.498-2.814; for 15-59 and over 60 years old, respectively), zero skin lesions (OR: 1.916; 95% CI: 1.522-2.413), leprosy reaction (OR: 1.528; 95% CI: 1.195-1.952), rural occupation (OR: 1.364; 95% CI: 1.128-1.650), Han ethnicity (OR: 1.268; 95% CI: 1.159-1.386), and male sex (OR: 1.128; 95% CI: 1.024-1.243). CONCLUSIONS: Delayed diagnosis, nerve damage, no skin lesions, WHO and Ridley-Jopling classifications, leprosy reactions, advanced age, rural occupation, Han ethnicity, and male sex were associated with disability in leprosy patients. Identifying risk factors could help to prevent physical disability.

Aucklandia costus (Syn. Saussurea costus): Ethnopharmacology of an endangered medicinal plant of the himalayan region.

ETHNOPHARMACOLOGICAL RELEVANCE: Aucklandia costus Falc. a medicinal plant is native to the Himalayan region and synonymous with Saussurea costus, Saussurea lappa, and Aucklandia lappa. It has an ancient background of being used ethnopharmacologically for various body ailments. According to Ayurveda, Unani, Siddha, and Traditional Chinese Medicine, Costus roots are recommended for leukoderma, liver, kidney, blood disorders, Qi stagnation, and tridosha. Root and powder are used orally with warm water to cure gastric problems, and the paste is applied to the inflamed area to relieve pain. Root paste is applied on the skin to cure boils, blisters, and leprosy. AIM OF THE STUDY: The aim of the present review is to establish a correlation among the ethnopharmacological uses and scientific studies conducted on A. costus with chemical constituents, safety & toxicity data including future directions for its conservation with higher yield and effect. MATERIALS AND METHODS: The study was conducted by studying books, research papers, and literature in history, agroforestry, phytopharmacology of Himalayan plants using international databases, publication, Red data book, and reports. The search engines: Pubmed, Scopus, Wiley Inter-science, Indian Materia Medica, Science Direct, and referred journals are referenced. RESULTS: The literature collected from databases, journals, websites, and books mentioned the use of costus roots in local and traditional practices. CITES included A. costus in a critically endangered category due to lack of cultural practices and overexploitation from wild. A. costus roots are known since 13th century for use in ancient Ayurvedic products but the scientific evaluation is of future research interest. A correlation of traditional uses with scientific studies has been explored to assess the effect of root powder, extract, oil and isolated constituents: Costunolids, Saussureamine B and Dehydrocostus lactone etc. in gastric ulceration and lesions; inhibition of antigen-induced degranulation, mucin production, number of immune cells, eosinophils, and expression and secretion of Th2 cytokines (IL-4 and IL-13) in asthma. The inhibition of pro-inflammatory mediators is also reported by Cynaropicrin, Alantolactone, Caryophyllene, Costic acid. Also, the sesquiterpene lactones has profound effect in inhibition of inflammatory stages and induced apoptotic cascades in cancer. Very few data on the safety and toxicity of plant parts have been noted which needs to be evaluated scientifically. CONCLUSION: A. costus have been noted to have remarkable effect for gastric, hepatic, inflammatory, respiratory, cancer, skin problems but there were several errors in selection of plant material, authentification, selection of dose, assessment, selection of standard and control have been identified. Therefore, a schematic drug development and research strategy exploiting the potential of plant extract, fraction, products and probable constituents, costunolide, dehydrocostus lactone, cynaropicrin, saussureamine assuring dose-response relationship and safety may be determined under pre-clinical which may be extrapolated to clinical level. An evaluation of phytochemicals in A. costus collected from different geographical location in Himalayas may be drawn to identify and conserve the higher yielding plant.

A pleiotropic effect of the APOE gene: association of APOE polymorphisms with multibacillary leprosy in Han Chinese from Southwest China.

BACKGROUND: Patients with leprosy have a very low risk of Alzheimer disease (AD) and ß-amyloid (Aß) deposition is significantly lower in the brain tissue of elderly patients with leprosy compared with age-matched controls. Apolipoprotein E (ApoE) plays a critical role in lipid metabolic pathways and in the brain, facilitating the proteolytic clearance of Aß. We hypothesized that APOE confers risk of leprosy as lipid metabolism is involved in Mycobacterium leprae infection. OBJECTIVES: To investigate the potential genetic associations between APOE and leprosy in two independent Chinese case-control cohorts from the Yuxi and Wenshan prefectures, Yunnan Province of Southwest China. METHODS: Five APOE single-nucleotide polymorphisms (SNPs) were analysed in 1110 individuals (527 patients and 583 controls) from the Yuxi prefecture using a SNaPshot assay. Genetic variations in the entire APOE exons were screened in 1788 individuals (798 patients and 990 controls) from the Wenshan prefecture using next-generation sequencing technology. RESULTS: The AD-associated SNPs rs405509 and rs439401 increased the risk of leprosy per se and multibacillary leprosy (P < 0·005), but the APOE-ε4 allele did not. The SNPs rs405509 and rs439401 were cis expression quantitative trait loci (eQTL) for APOE expression in human skin. Differential APOE mRNA expression was observed in skin lesions of patients with type I reaction leprosy and those with multibacillary leprosy. APOE and related lipid genes are involved in an interaction network with leprosy susceptibility genes. CONCLUSIONS: The APOE gene is associated with leprosy, most likely by regulating lipid-metabolism-related genes.

Chinese version of the treatment of autoimmune bullous disease quality of life questionnaire: Reliability and validity.

BACKGROUND: Treatments for autoimmune blistering disease carry significant risks of medical complications and can affect the patient's quality of life. Recently, the Treatment of Autoimmune Bullous Disease Quality of Life questionnaire was developed in Australia. OBJECTIVE: The objective of this study was to evaluate the reliability and validity of the Chinese version of the Treatment of Autoimmune Bullous Disease Quality of Life questionnaire in Chinese patients with autoimmune blistering diseases. METHODS: The Chinese version of the Treatment of Autoimmune Bullous Disease Quality of Life questionnaire was produced by forward-backward translation and cross-cultural adaptation of the original English version. Autoimmune blistering disease patients recruited in the study self-administered the Chinese Treatment of Autoimmune Bullous Disease Quality of Life questionnaire, the Dermatology Life Quality Index and the 36-item Short-Form Health Survey. Reliability of the Chinese Treatment of Autoimmune Bullous Disease Quality of Life was evaluated using internal consistency and test-retest (days 0 and 7) methods. Validity was analyzed by face, content, construct, convergent and discriminant validity measures. RESULTS: A total of 86 autoimmune blistering disease patients were recruited for the study. Cronbach's alpha coefficient was 0.883 and the intraclass correlation coefficient was 0.871. Face and content validities were satisfactory. Convergent validity testing revealed correlation coefficients of 0.664 for the Treatment of Autoimmune Bullous Disease Quality of Life and Dermatology Life Quality Index and -0.577 for the Treatment of Autoimmune Bullous Disease Quality of Life and 36-item Short-Form Health Survey. With respect to discriminant validity, no significant differences were observed in the Treatment of Autoimmune Bullous Disease Quality of Life scores of men and women (t = 0.251, P = 0.802), inpatients and outpatients (t = 0.447, P = 0.656), patients on steroids and steroid-sparing medications (t = 0.672, P = 0.503) and patients with different autoimmune blistering disease subtypes (F = 0.030, P = 0.971). LIMITATIONS: Illiterate patients were excluded from the study. The patients were from a single hospital and most of their conditions were in a relatively stable status. CONCLUSION: The Chinese version of the Treatment of Autoimmune Bullous Disease Quality of Life questionnaire is a reliable and valid instrument to measure treatment burden and to serve as an end point in clinical trials in Chinese autoimmune blistering disease patients.

Tuberculosis risk-associated single nucleotide polymorphisms do not show association with leprosy in Chinese population.

OBJECTIVE: Leprosy and tuberculosis (TB) are chronic granulomatous infectious diseases. As well as pathogen and environmental factors, host genetic factors make a substantial contribution to susceptibility to both diseases. More importantly, leprosy and TB also have pathogenic mechanisms and clinical features in common. In this study, the genetic association between leprosy and TB was investigated in a Chinese Han population. METHODS: A genetic association study that included 46 TB susceptibility single nucleotide polymorphisms (SNPs) was performed, involving 1150 leprosy cases and 1150 controls from the Chinese Han population. The Sequenom MassARRAY system was used. RESULTS: No significant association was found between the 46 SNPs and leprosy. Therefore, according to the present study, there is no shared susceptibility locus between leprosy and TB in the Chinese Han population. CONCLUSIONS: Although leprosy and TB have a number of similar characteristics, no shared susceptibility loci were found in the Chinese Han population. Thus, this study demonstrated that the genetic basis of the pathogenesis of the two diseases may vary greatly.

Genetic variants of the MRC1 gene and the IFNG gene are associated with leprosy in Han Chinese from Southwest China.

Leprosy is an ancient infectious disease, with over 200,000 affected people (mainly in Asia and Africa) being registered annually. Genetic factors may confer susceptibility to this disease. In the present study, we genotyped 12 genetic variants of the MRC1 gene and the IFNG gene in 527 Han Chinese with leprosy and 583 healthy individuals from Yunnan, China, to discern potential association of these two genes with leprosy. In particular, we aimed to validate the recently reported association of MRC1 variant rs1926736 (p.G396S) and IFNG variant rs2430561 (+874 T>A) with leprosy, which were initially observed in Vietnamese and Brazilian populations, respectively. Our results failed to confirm the reported association between variants rs1926736 and rs2430561 and leprosy in Han Chinese. However, we found that variants rs692527 (P = 0.022) and rs34856358 (P = 0.022) of the MRC1 gene were associated with paucibacillary leprosy, and rs3138557 of the IFNG gene was significantly associated with multibacillary leprosy. The exact role of the MRC1 gene and the IFNG gene in leprosy awaits future study.

Granulomatous reaction to intradermal injection of lepromin (Mitsuda reaction) is linked to the human NRAMP1 gene in Vietnamese leprosy sibships.

The Mitsuda test, which measures the specific immune response against intradermally injected lepromin, has a high prognostic value for susceptibility or resistance to the lepromatous form of leprosy. A sib-pair linkage analysis between the Mitsuda response and the NRAMP1 gene was done among 20 nuclear families with leprosy (totaling 118 sibs) from Ho Chi Minh City, Vietnam. All family subjects were genotyped for several intragenic and flanking NRAMP1 markers, leading to the definition of a fully informative NRAMP1 haplotype. Significant linkage was observed between NRAMP1 and Mitsuda reaction when considered either as a quantitative (P<.002) or as a categorical (P=.001) trait. Separate analyses among healthy and affected sibs showed evidence for linkage in both subsamples, indicating that linkage between the Mitsuda reaction and NRAMP1 is independent of leprosy status. These results support the view that NRAMP1 plays a regulatory role for the development of acquired antimycobacterial immune responses as determined by in vivo Mitsuda test reaction.

Granulomatous reaction to intradermal injection of lepromin (Mitsuda reaction) is linked to the human NRAMP1 gene in Vietnamese leprosy

The Mitsuda test, which measures the specific immune response against intradermally injected lepromin, has a high prognostic value for susceptibility or resistance to the lepromatous form of leprosy. A sib-pair linkage analysis between the Mitsuda response and the NRAMP1 gene was done among 20 nuclear families with leprosy (totaling 118 sibs) from Ho Chi Minh City, Vietnam. All family subjects were genotyped for several intragenic and flanking NRAMP1 markers, leading to the definition of a fully informative NRAMP1 haplotype. Significant linkage was observed between NRAMP1 and Mitsuda reaction when considered either as a quantitative (P<.002) or as a categorical (P=.001) trait. Separate analyses among healthy and affected sibs showed evidence for linkage in both subsamples, indicating that linkage between the Mitsuda reaction and NRAMP1 is independent of leprosy status. These results support the view that NRAMP1 plays a regulatory role for the development of acquired antimycobacterial immune responses as determined by in vivo Mitsuda test reaction.

BC's "Island of death" marked a sad chapter in Canada's medical history.

Although the first case of leprosy in Canada was detected in 1815 in New Brunswick, the saddest chapter concerning the disease's history in Canada did not open until the late 1800s when leprosy was discovered among Chinese migrant workers on Canada's West Coast--a chapter that was not closed until 1957. Penelope Johnston relates the story of British Columbia's "Island of Death," where lepers used to be quarantined.

Complex segregation analysis of leprosy in southern Vietnam.

To investigate the nature of the genetic component controlling susceptibility to leprosy and its subtypes, 402 nuclear families were ascertained through a leprosy patient followed at the Dermatology Hospital in Ho Chi Minh City, Vietnam; 285 families were of Vietnamese origin and 117 were of Chinese origin with a higher proportion of lepromatous forms among Chinese patients. Segregation analyses were conducted using the model developed by Abel and Bonney [(1990) Genet Epidemiol 7:391-407], which accounted for variable age of onset and time-dependent covariates. Three phenotypes were considered: leprosy per se (all forms of leprosy together), nonlepromatous leprosy, and lepromatous leprosy. For each of this phenotype, analyses were performed on the whole sample and separately on the Vietnamese and the Chinese families. The results showed that a single Mendelian gene could not account for the familial distributions of leprosy per se and its two subtypes in the whole sample. However, these results were different according to the ethnic origin of the families. In the Vietnamese subsample, there was evidence for a codominant major gene with residual familial dependences for the leprosy per se phenotype, and borderline rejection of the Mendelian transmission hypothesis for the nonlepromatous phenotype. In Chinese families, strong rejection of Mendelian transmission was obtained in the analysis of leprosy per se, and no evidence for a familial component in the distribution of the nonlepromatous phenotype was observed. For the lepromatous phenotype, the discrimination between models was poor, and no definitive conclusion could be reached. Referring to immunological data, we suggest that these results could be explained by a heterogeneity in the definition of the lepromatous phenotype. It is likely that progress in the understanding of the genetic components involved in the expression of leprosy will come from a better definition of the phenotype under study, and immunological studies are ongoing in this population to investigate this hypothesis.

Short-term multidrug therapy in multibacillary leprosy - review of 80 cases in two province of China (1983-1988)

Thirty-three active multibacillary patients from nine counties of Weifang Prefecture, Shandong Province, and 47 active cases from Menla County, Yunnan Province, People's Republic of China, were treated with 24 and 27 months of multidrug therapy (MDT), respectively, in 1983. Clinical assessments, smears, and histopathologic examinations were carried out independently by study teams from the Institutes of Dermatology of these two provinces. Reexaminations at 12-14 months and at termination of therapy showed marked improvement, and there was continued improvement at 12-18 and 33 months on follow up. Conversion of the bacterial index to negativity was 0/33, 5/47 for the patients from Shandong and Yunnan provinces, respectively, at the end of MDT and 2/33 at 12 months' and 17/47 at 18 months' follow up, which increased to 21/33 and 26/44 at 33 months' follow up. Regression of specific infiltration was about 21%-100% after 24-27 months of MDT; further regression to 95%-100% occurred at 33 months' follow up

An immunohistochemical and morphological study of amyloidosis complicating leprosy in Malaysian patients.

Congo red screening of tissue blocks from 37 consecutive autopsies on leprosy patients revealed 7 cases of systemic amyloidosis, indicating a prevalence rate of 19%. 5 were males and 2 females. All were ethnic Chinese. Their ages ranged from 52 to 85 years with a mean of 69 years. Six had lepromatous leprosy while the remaining 1 had tuberculoid leprosy. In all 7 cases, the amyloid was AA in type, being permanganate-sensitive and immunoreactive with anti-human AA protein antiserum. Hepatic deposition was limited to blood vessels, a pattern typical of AA (secondary) amyloidosis. With regard to renal involvement, 4 showed a predominantly vascular pattern of infiltration while 3 exhibited the more ominous glomerular pattern. Three died of chronic renal failure and 2 of congestive cardiac failure attributable to renal and cardiac amyloidosis respectively. One patient succumbed to septicaemia and the remaining 1 to acute myocardial infarction. AA amyloidosis remains a serious and significant complication of leprosy among Malaysians.

HLA and skin disease in the Chinese.

The HLA associations in skin diseases among the Chinese were reviewed. Tuberculoid leprosy was associated with B17 (RR = 4.1). This HLA association was reinforced in the finding of excess HLA haplotype sharing among affected siblings in multiple case families. In psoriasis the associations were with A1, AW30 and B13. The relative risk associated with AW30, B13 was 16.1. In SLE, mild patients were associated with B13 (RR = 3.7) and severe patients with B17.

Factors influencing the outcome of health campaigns: a case study in Singapore.

Singapore, located in South-east Asia, enjoys a high standard of health care. However, certain diseases are still of major concern to the health authorities, who feel these could be more easily controlled if the public were more aware of their modes of transmission. A "Combat infectious diseases" campaign was therefore launched to educate the public on food-borne diseases (cholera, enteric fever), malaria, dengue/dengue haemmorrhagic fever, leprosy, tuberculosis, and sexually transmitted diseases (syphilis, gonorrhoea). Educational activities in the form of talks, film shows and exhibitions in schools, community centres and other institutions were carried out over a 15-month period. This paper analyzes some of the factors which affected the results of the campaign, as revealed by a health survey conducted in a selected lower-middle income urban community, where sub-groups of the adult population (aged above 15) were tested to assess their health knowledge. Findings indicate that educational level, age of respondents and language proficiency--four languages are used in Singapore--seem to be the three variables that affect the likelihood of the respondents' receptivity to campaign information.