Objective. So far, it has not been established a satisfactory method for early diagnosis and studying on epidemiology for leprosy, we want to develop a molecular biological method for solv...Objective. So far, it has not been established a satisfactory method for early diagnosis and studying on epidemiology for leprosy, we want to develop a molecular biological method for solving this point. Materials and methods. Based on the M. leprae gene coding groEL, 65kD and 16S rRNA, three polymerase chain reactions were developed by using plikaytis’, Woods’ and Pattyn’s procedures. It was optimized that the experimental parameters for each PCR, and a comparative study on practivity among three PCRs was also conducted for practical purpose.Results and conclusion. For detecting infection with M. leprae, all of PCRs established by us were highly sensitive and specific, but for practicl purpose, the woods’ PCR optimized by us ought to be chosen firstly.展开更多
Immune-deficient nude mice were inoculated with nude mouse derived Mycobacteriurn leprae by multiple routes (intravenously. subcutaneously at the foot pads and ears). The results showed that these inoculated animals w...Immune-deficient nude mice were inoculated with nude mouse derived Mycobacteriurn leprae by multiple routes (intravenously. subcutaneously at the foot pads and ears). The results showed that these inoculated animals were capable of producing a great number of Mycobacterium leprae to a level 10(11-12) per gram of tissue. and were detected histopathologically to have heavy leproniatous lesions. The dissemination of the infection was found particularly in sites with lower body temperature.The organisms have a partiality to striated muscles and peripheral nerves. The authors suggest that experimental leprosy in nude mice is a very useful tool for leprosy resarch. especially in countries without armadillos. Compared with the single-route inoculation reported previously. multiple-route inoculation is more available.展开更多
INTRODUCTIONLeprosy caused by Mvcobacterium leprae （M. leprae）, is a chronic granulomatous disease affecting the skin and peripheral nervous system, which is transmitted through direct contact with nontreated or ina...INTRODUCTIONLeprosy caused by Mvcobacterium leprae （M. leprae）, is a chronic granulomatous disease affecting the skin and peripheral nervous system, which is transmitted through direct contact with nontreated or inadequate treatment patients. Diagnosis of leprosy depends on the clinical signs and symptoms and slit skin smear positivity. However, it＇s sometimes similar with other granulomatous disease caused by mycobacterial infection. Early stage leprosy is difficult to diagnose by clinical criterion alone because the sensitivity of acid-fast bacilli staining is quite low. The polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） shows the great advantage in rapid identification and diagnosis for early cases and has a differentiation between leprosy and nonleprosy cases.展开更多
Background Detection of infection with Mycobacterium leprae allows timely prophylactic treatment,thereby reducing transmission as well as the risk of permanent,leprosy-associated nerve damage.However,since there is no...Background Detection of infection with Mycobacterium leprae allows timely prophylactic treatment,thereby reducing transmission as well as the risk of permanent,leprosy-associated nerve damage.However,since there is no worldwide-implemented standard test for M.leprae infection,detection of infection in asymptomatic individuals remains a major challenge for control programs in endemic areas.In previous studies,we developed and fiield-tested a lateral flow assay(LFA)quantitatively detecting human IgM against M./eprae-specific phenolic glycolipid I(anti-PGL-I),a marker for both active and past infection.This rapid test utilizes luminescent,background-free,up-converting reporter particles(UCP)and immunochromatography(i.e.the UCP-LF test platform)for accurate quantitation of anti-PGL-I IgM without operator bias.The aim of this study was to evaluate the final version of this quantitative UCP-based rapid test(i.e.PGL-I QURapid),using serum and fingerstick blood(FSB).Methods The test comprises a lateral flow strip,in a standard plastic or biodegradable cassette.It can be provided with a humanized,recombinant control to monitor test performance and calculate accurate anti-PGL-I IgM levels.The performance of this QUR-test was assessed using serum and FSB from patients with leprosy(n=214),tubercu-losis(n=20),buruli ulcer(n=19),leishmaniasis(n=14),non-tuberculous mycobacterial(n=35)infections,as well as healthy Dutch individuals(n=710)and humanized,recombinant anti-PGL-I IgM antibodies.Plot receiver operating characteristic curves were created and sensitivity(Sn),specificity(Sp)and the area under the curve were calculated to evaluate test performance.Results Test results classified multibacillary leprosy patients with 95.0%Sn and 100%Sp using serum and 91.5%Sn and 99.8%Sp using FSB.Qualitative test results could be read after 2 min flow time,with accurate quantitation from 10 min onwards.The new anti-PGL-I IgM control supports production of batches with predetermined seroposi-tivity thresholds and monitoring of the PGL-I QUR-test in various settings.Conclusion The operational version of the PGL-I QURapid with point-of-care applicability,meets the WHO target product profile criteria.Thus,this QUR-test is ready for public health implementations.展开更多
Leprosy is a communicable disease which can cause hideous deformities to the afflicted and social stigmatization to them and their families. The continued high endemicity of leprosy in pockets of Sub-Saharan Africa is...Leprosy is a communicable disease which can cause hideous deformities to the afflicted and social stigmatization to them and their families. The continued high endemicity of leprosy in pockets of Sub-Saharan Africa is a source of bafflement to researchers. In this paper, we investigate non-compliant behavior by patients on treatment and possible inadequacy of the prescribed treatments as the reason for the persistence of the disease in the region. We construct theoretical, deterministic mathematical models of the transmission dynamics of leprosy. These models are modified to encapsulate non-compliance and inadequate treatment. The models are then analyzed to gain insight into the qualitative features of the equilibrium states, which enable us to determine the basic reproduction number. We also employ analytical and numerical techniques to investigate the impact of non-compliance and inadequate treatment on the transmission dynamics of the disease. Our results show that, as long as there is treatment, leprosy will eventually be eliminated from the region and that the disposition under investigation only serves to slow the rate at which the disease is eradicated.展开更多
BACKGROUND Leprosy is a disease caused by Mycobacterium leprae(M.leprae),an intracellular pathogen that has tropism and affects skin and nervous system cells.The disease has two forms of presentation:Paucibacillary an...BACKGROUND Leprosy is a disease caused by Mycobacterium leprae(M.leprae),an intracellular pathogen that has tropism and affects skin and nervous system cells.The disease has two forms of presentation:Paucibacillary and multibacillary,with different clinical and immunological manifestations.Unlike what occurs in the multibacillary form,the diagnostic tests for the paucibacillary form are nonspecific and not very sensitive,allowing the existence of infected individuals without treatment,which contributes to the spread of the pathogen in the population.To mitigate this contamination,more sensitive diagnostic tests capable of detecting paucibacillary patients are needed.AIM To predict the three-dimensional structure models of M.leprae antigens with serodiagnostic potential for leprosy.METHODS In this in silico study,satisfactory templates were selected in the Protein Data Bank(PDB)using Basic Local Alignment Search Tool to predict the structural templates of ML2038,ML0286,ML0050,and 85B antigens by comparative modeling.The templates were selected according to general criteria such as sequence identity,coverage,X-ray resolution,Global Model Quality Estimate value and phylogenetic relationship;Clustal X 2.1 software was used in this analysis.Molecular modeling was completed using the software Modeller 9v13.Visualization of the models was made using ViewerLite 4.2 and PyMol software,and analysis of the quality of the predicted models was performed using the QMEAN score and Z-score.Finally,the three-dimensional moels were validated using the MolProbity and Verify 3D platforms.RESULTS The three-dimensional structure models of ML2038,ML0286,ML0050,and 85B antigens of M.leprae were predicted using the templates PDB:3UOI(90.51%identity),PDB:3EKL(87.46%identity),PDB:3FAV(40.00%identity),and PDB:1F0N(85.21%identity),respectively.The QMEAN and Z-score values indicated the good quality of the structure models.These data refer to the monomeric units of antigens,since some of these antigens have quaternary structure.The validation of the models was performed with the final three-dimensional structure-monomer(ML0050 and 85B antigens)and quaternary structures(ML2038 and ML0286).The majority of amino acid residues were observed in favorable and allowed regions in the Ramachandran plot,indicating correct positioning of the side chain and absence of steric impediment.The MolProbity score value and Verify 3D results of all models indicated a satisfactory prediction.CONCLUSION The polarized immune response against M.leprae creates a problem in leprosy detection.The selection of immunodominant epitopes is essential for the development of more sensitive serodiagnostic tests,for this it is important to know the three-dimensional structure of the antigens,which can be predicted with bioinformatics tools.展开更多
Leprosy is characterized by skin lesions and peripheral nerve damage. It may take a long time before the diagnosis can be confirmed if the patients have no typical skin involvements. Here we report an unusual case. A ...Leprosy is characterized by skin lesions and peripheral nerve damage. It may take a long time before the diagnosis can be confirmed if the patients have no typical skin involvements. Here we report an unusual case. A 40-year-old male with lepromatous leprosy showed a gradual onset of bilateral symmetrical neuropathies without characteristic skin manifestations seven years after onset and with pulmonary tuberculosis simultaneously. He was misdiagnosed as having Guillani-Barr6 syndrome and systemic necrotizing vasculitis for 10 years until the skin biopsy was performed. This case indicates that the risk of leprosy exists, though new cases being detected have significantly declined over the last 50 years; neurologists need to pay more attention to leprosy with various manifestations .展开更多
Leprosy,a disease caused by Mycobacterium leprae,can destroy susceptible individuals’skin and peripheral nerves,ultimately leading to disfigurement.Due to its symptoms,it has been stigmatized since ancient times.As r...Leprosy,a disease caused by Mycobacterium leprae,can destroy susceptible individuals’skin and peripheral nerves,ultimately leading to disfigurement.Due to its symptoms,it has been stigmatized since ancient times.As recently as the 1950s,there were nearly 400,000 leprosy patients in China.展开更多
Background Leprosy remains a persistent public health challenge,where human-to-human transmission of Mycobacterium leprae via respiratory droplets is well established.In the tropical Americas,growing evidence implicat...Background Leprosy remains a persistent public health challenge,where human-to-human transmission of Mycobacterium leprae via respiratory droplets is well established.In the tropical Americas,growing evidence implicates armadillos as important zoonotic reservoirs,particularly through direct contact during hunting and handling.However,such transmission has so far been considered rare and highly localised.This study provides a comprehensive spatial analysis of the role of armadillo hunting in human leprosy transmission,quantifying its contribution to disease prevalence and identifying geographic hotspots where interventions could be most effective.Methods Using Brazil’s 326,001 reported leprosy cases from 2013 to 2022,we applied a pathogeographical approach to explore transmission dynamics.We compiled data on 554 hunted armadillos across 175 municipalities and M.leprae prevalence in 376 armadillo individuals from 97 municipalities(mean prevalence=38.5%).These were used to build spatial models assessing hunting-related infection risk and integrated as a variable into a generalised linear model alongside socioeconomic,climatic,and environmental predictors to evaluate their effects on human leprosy prevalence.Results Key predictors of armadillo hunting included higher population density(P<0.001)and firearm availability(P<0.01).Infection in armadillos was negatively correlated with native habitat coverage(coefficient:−2.28;P<0.001),suggesting that environmental degradation can amplify infection risk.The armadillo-hunting infection risk variable—generated by combining armadillo hunting and infection favourability models—emerged as the second strongest predictor of human leprosy prevalence(coefficient:1.69;P<0.001),accounting for~25%of cases nationally and around 40%in deforestation hotspots.Additional positive predictors included greater precipitation seasonality(coefficient:0.82;P<0.001)and malnutrition(coefficient:0.01;P<0.001),while higher population density(coefficient:−0.64;P<0.001),natural habitat coverage(coefficient:−0.50;P<0.001)and socioeconomic status(coefficient:−0.47;P=0.013)were linked to reduced disease prevalence.Conclusions Armadillo hunting seems to play a more significant role in human leprosy transmission than previously recognised.To address this overlooked pathway,targeted interventions should focus on reducing unsafe and illegal hunting,improving communication around zoonotic risks,strengthening disease surveillance in high-risk areas,and conducting genetic studies to confirm wildlife-to-human transmission.Our findings highlight the importance of incorporating wildlife-associated transmission pathways into strategies to reduce disease prevalence and mitigate future outbreaks in tropical regions facing rapid environmental change and persistent poverty.展开更多
Introduction:Type II lepra reaction(T2LR)is a rare immune-mediated complication in patients with leprosy and is typically treated with glucocorticoids and thalidomide.Idiopathic intracranial hypertension(IIH)is marked...Introduction:Type II lepra reaction(T2LR)is a rare immune-mediated complication in patients with leprosy and is typically treated with glucocorticoids and thalidomide.Idiopathic intracranial hypertension(IIH)is marked by increased intracranial pressure leading to symptoms like headache and vision loss.Here,we report a rare case of concomitant T2LR and IIH.Case presentation:A 35-year-old woman with leprosy had been treated with corticosteroids and thalidomide for T2LR over a period of 2 years.She subsequently experienced progressive vision loss,which was initially misdiagnosed as optic neuritis.After high-dose glucocorticoid treatment,her condition worsened.The patient was later found to have elevated intracranial pressure and was ultimately diagnosed with IIH.She was treated with cerebrospinal fluid diversion,which relieved her symptoms.The patient was mildly obese and had received high-dose corticosteroids.T2LR is associated with increased proinflammatory cytokine levels,so the IIH condition was speculated to be related to T2LR.Discussion:Evidence suggests that inflammatory mediators in T2LR may increase choroid plexus permeability,raising intracranial pressure.Long-term glucocorticoid use is associated with IIH,as it may increase intracranial pressure through local cortisol activation in the choroid plexus.The patient’s misdiagnosis of optic neuritis,due to a lack of typical IIH symptoms,delayed appropriate treatment and led to vision loss.Conclusion:While this case may represent an extreme instance as T2LR and IIH are both rare conditions,it highlights a broader issue:prolonged steroid use can increase intracranial pressure to varying degrees,however not all patients with elevated intracranial pressure experience headaches.This case emphasizes the importance of considering IIH in patients on chronic corticosteroids treatment presenting with unusual vision changes.Clinicians should be aware of this possibility and conduct thorough evaluations for high risk populations to detect such complications.展开更多
Background: Leprosy is a chronic infectious disease classified into two subgroups for therapeutic purposes:paucibacillary(PB)and multibacillary(MB),closely related to the host immune responses.In this context it is no...Background: Leprosy is a chronic infectious disease classified into two subgroups for therapeutic purposes:paucibacillary(PB)and multibacillary(MB),closely related to the host immune responses.In this context it is noteworthy looking for immunological biomarkers applicable as complementary diagnostic tools as well as a laboratorial strategy to follow-up leprosy household contacts.Methods:: The cross-sectional study enrolled 49 participants,including 19 patients and 30 healthy controls.Peripheral blood mononuclear cells(PBMC)were isolated and incubated in the presence of Mycobacterium leprae bacilli.The cells were prepared for surface(CD4+and CD8+)and intracytoplasmic cytokine staining(IFN-γ,IL-4 and IL-10).Multiple comparisons amongst groups were carried out by ANOVA,Kruskal–Wallis,Student T or Mann–Whitney test.Comparative analysis of categorical variables was performed by Chi-square.Functional biomarker signature analysis was conducted using the global median values for each biomarker index as the cut-off edge to identify the proportion of subjects with high biomarker levels.Results: The cytokine signature analysis demonstrated that leprosy patients presented a polyfunctional profile of T-cells subsets,with increased frequency of IFN-γ+T-cell subsets along with IL-10+and IL-4+from CD4+T-cells,as compared to health Controls(Venn diagram report).Moreover,statistical analysis was carried out using parametric or non-parametric variance analysis followed by pairwise multiple comparisons,according to the data normality distribution.L(PB)displayed a polyfunctional profile characterized by enhanced percentage of IFN-γ+,IL-10+and IL-4+produced by most T-cell subsets,as compared to L(MB)that presented a more restricted cytokine functional profile mediated by IL-10+and IL-4+T-cells with minor contribution of IFN-γproduced by CD4+T-cells.Noteworthy was that HHC(MB)exhibited enhanced frequency of IFN-γ+T-cells,contrasting with HHC(PB)that presented a cytokine profile limited to IL-10 and IL-4.Conclusions: Our data demonstrated that L(PB)displayed enhanced percentage of IFN-γ+,IL-10+and IL-4+as compared to L(MB)that presented functional profile mediated by IL-10+and IL-4+T-cells and HHC(MB)exhibited enhanced frequency of IFN-γ+T-cells,contrasting with HHC(PB).Together,our findings provide additional immunological features associated with leprosy and household contacts.These data provide evidence that biomarkers of immune response can be useful complementary diagnostic/prognostic tools as well as insights that household contacts should be monitored to access putative subclinical infection.展开更多
Leprosy is an infectious granulomatous disease caused by Mycobacterium leprae that affects the skin and can lead to deformity by damaging peripheral nerves.Although leprosy is no longer an incurable disease,its epidem...Leprosy is an infectious granulomatous disease caused by Mycobacterium leprae that affects the skin and can lead to deformity by damaging peripheral nerves.Although leprosy is no longer an incurable disease,its epidemic has not been well controlled because of its unclear routes of transmission and the lack of an effective vaccine.Moreover,leprosy has long been an ideal disease model for the study of genetics and immunology of infectious diseases due to its strong genetic predisposition and immune-dependent spectrum of clinical manifestations.Here,we review the latest and important findings of the pathogenesis of leprosy.Recent studies have shown that the highly conserved M.leprae is zoonotic,which further complicates the ambiguous transmission of M.leprae.Genetically,genome-wide association studies of leprosy have reported dozens of susceptibility genes,most of which are immune-related,and thus systematically elucidate the immunogenetic basis of the disease.Immunologically,plenty of novel mechanisms of host defense against intracellular bacterial infection and the modulation of host immunity by M.leprae have been depicted.Despite these great achievements,there are still gaps between pathogenic biology,genetics,and immunology of leprosy,limiting our in-depth understanding of leprosy pathogenesis.Further efforts,such as multi-omics data integration and the development of viable animal models for immunogenetic studies are urgently needed to accelerate advances in the precise prevention and treatment of leprosy.展开更多
Background: Leprosy control achieved dramatic success in the 1980s–1990s with the implementation of short course multidrug therapy,which reduced the global prevalence of leprosy to less than 1 in 10000 population.How...Background: Leprosy control achieved dramatic success in the 1980s–1990s with the implementation of short course multidrug therapy,which reduced the global prevalence of leprosy to less than 1 in 10000 population.However,a period of relative stagnation in leprosy control followed this achievement,and only limited further declines in the global number of new cases reported have been achieved over the past decade.Main text In 2016,major stakeholders called for the development of an innovative and comprehensive leprosy strategy aimed at reducing the incidence of leprosy,lowering the burden of disability and discrimination,and interrupting transmission.This led to the establishment of the Global Partnership for Zero Leprosy(GPZL)in 2018,with partners aligned around a shared Action Framework committed to achieving the WHO targets by 2030 through national leprosy program capacity-building,resource mobilisation and an enabling research agenda.GPZL convened over 140 experts from more than 20 countries to develop a research agenda to achieve zero leprosy.The result is a detailed research agenda focusing on diagnostics,mapping,digital technology and innovation,disability,epidemiological modelling and investment case,implementation research,stigma,post exposure prophylaxis and transmission,and vaccines.This research agenda is aligned with the research priorities identified by other stakeholders.Conclusions: Developing and achieving consensus on the research agenda for zero leprosy is a significant step forward for the leprosy community.In a next step,research programmes must be developed,with individual components of the research agenda requiring distinct expertise,varying in resource needs,and operating over different timescales.Moving toward zero leprosy now requires partner alignment and new investments at all stages of the research process,from discovery to implementation.展开更多
Objective:This study was performed to compare the efficacy and safety of methotrexate(MTX)plus prednisolone versus prednisolone monotherapy in patients with erythema nodosum leprosum(ENL).Methods:This comparative clin...Objective:This study was performed to compare the efficacy and safety of methotrexate(MTX)plus prednisolone versus prednisolone monotherapy in patients with erythema nodosum leprosum(ENL).Methods:This comparative clinical study was performed in the Chittagong Medical College Hospital,Bangladesh from June 2018 to December 2019.Nineteen patients were selected according to inclusion criteria and randomly allocated to either the MTX plus prednisolone group(Group A,n=10)or the prednisolone monotherapy group(Group B,n=9).All patients were followed up until the end of the 6-month duration of therapy to observe the clinical outcomes and adverse effects.Results:All patients in both groups showed significant improvement(P=0.005 and P=0.008 in Group A and B,respectively).However,prednisolone-related adverse events were more frequent in Group B.Conclusion:The present study has demonstrated that a combination of prednisolone and MTX is a safer and more effective treatment than steroid monotherapy in ENL patients including the healing of nodules.However,this combination therapy did not appear to have a significant steroid-sparing effect,possibly because of the small sample size and short study period.Therefore,a well-designed multicenter randomized controlled trial is recommended for validation of MTX with prednisolone for the management of ENL.展开更多
文摘Objective. So far, it has not been established a satisfactory method for early diagnosis and studying on epidemiology for leprosy, we want to develop a molecular biological method for solving this point. Materials and methods. Based on the M. leprae gene coding groEL, 65kD and 16S rRNA, three polymerase chain reactions were developed by using plikaytis’, Woods’ and Pattyn’s procedures. It was optimized that the experimental parameters for each PCR, and a comparative study on practivity among three PCRs was also conducted for practical purpose.Results and conclusion. For detecting infection with M. leprae, all of PCRs established by us were highly sensitive and specific, but for practicl purpose, the woods’ PCR optimized by us ought to be chosen firstly.
文摘Immune-deficient nude mice were inoculated with nude mouse derived Mycobacteriurn leprae by multiple routes (intravenously. subcutaneously at the foot pads and ears). The results showed that these inoculated animals were capable of producing a great number of Mycobacterium leprae to a level 10(11-12) per gram of tissue. and were detected histopathologically to have heavy leproniatous lesions. The dissemination of the infection was found particularly in sites with lower body temperature.The organisms have a partiality to striated muscles and peripheral nerves. The authors suggest that experimental leprosy in nude mice is a very useful tool for leprosy resarch. especially in countries without armadillos. Compared with the single-route inoculation reported previously. multiple-route inoculation is more available.
基金The study was supported by a grant from the National Natural Science Foundation of China （No. 81271761）.
文摘INTRODUCTIONLeprosy caused by Mvcobacterium leprae （M. leprae）, is a chronic granulomatous disease affecting the skin and peripheral nervous system, which is transmitted through direct contact with nontreated or inadequate treatment patients. Diagnosis of leprosy depends on the clinical signs and symptoms and slit skin smear positivity. However, it＇s sometimes similar with other granulomatous disease caused by mycobacterial infection. Early stage leprosy is difficult to diagnose by clinical criterion alone because the sensitivity of acid-fast bacilli staining is quite low. The polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） shows the great advantage in rapid identification and diagnosis for early cases and has a differentiation between leprosy and nonleprosy cases.
基金This study was made possible thanks to a grant from the Q.M.Gastmann-Wichers foundation(AG).
文摘Background Detection of infection with Mycobacterium leprae allows timely prophylactic treatment,thereby reducing transmission as well as the risk of permanent,leprosy-associated nerve damage.However,since there is no worldwide-implemented standard test for M.leprae infection,detection of infection in asymptomatic individuals remains a major challenge for control programs in endemic areas.In previous studies,we developed and fiield-tested a lateral flow assay(LFA)quantitatively detecting human IgM against M./eprae-specific phenolic glycolipid I(anti-PGL-I),a marker for both active and past infection.This rapid test utilizes luminescent,background-free,up-converting reporter particles(UCP)and immunochromatography(i.e.the UCP-LF test platform)for accurate quantitation of anti-PGL-I IgM without operator bias.The aim of this study was to evaluate the final version of this quantitative UCP-based rapid test(i.e.PGL-I QURapid),using serum and fingerstick blood(FSB).Methods The test comprises a lateral flow strip,in a standard plastic or biodegradable cassette.It can be provided with a humanized,recombinant control to monitor test performance and calculate accurate anti-PGL-I IgM levels.The performance of this QUR-test was assessed using serum and FSB from patients with leprosy(n=214),tubercu-losis(n=20),buruli ulcer(n=19),leishmaniasis(n=14),non-tuberculous mycobacterial(n=35)infections,as well as healthy Dutch individuals(n=710)and humanized,recombinant anti-PGL-I IgM antibodies.Plot receiver operating characteristic curves were created and sensitivity(Sn),specificity(Sp)and the area under the curve were calculated to evaluate test performance.Results Test results classified multibacillary leprosy patients with 95.0%Sn and 100%Sp using serum and 91.5%Sn and 99.8%Sp using FSB.Qualitative test results could be read after 2 min flow time,with accurate quantitation from 10 min onwards.The new anti-PGL-I IgM control supports production of batches with predetermined seroposi-tivity thresholds and monitoring of the PGL-I QUR-test in various settings.Conclusion The operational version of the PGL-I QURapid with point-of-care applicability,meets the WHO target product profile criteria.Thus,this QUR-test is ready for public health implementations.
文摘Leprosy is a communicable disease which can cause hideous deformities to the afflicted and social stigmatization to them and their families. The continued high endemicity of leprosy in pockets of Sub-Saharan Africa is a source of bafflement to researchers. In this paper, we investigate non-compliant behavior by patients on treatment and possible inadequacy of the prescribed treatments as the reason for the persistence of the disease in the region. We construct theoretical, deterministic mathematical models of the transmission dynamics of leprosy. These models are modified to encapsulate non-compliance and inadequate treatment. The models are then analyzed to gain insight into the qualitative features of the equilibrium states, which enable us to determine the basic reproduction number. We also employ analytical and numerical techniques to investigate the impact of non-compliance and inadequate treatment on the transmission dynamics of the disease. Our results show that, as long as there is treatment, leprosy will eventually be eliminated from the region and that the disposition under investigation only serves to slow the rate at which the disease is eradicated.
文摘BACKGROUND Leprosy is a disease caused by Mycobacterium leprae(M.leprae),an intracellular pathogen that has tropism and affects skin and nervous system cells.The disease has two forms of presentation:Paucibacillary and multibacillary,with different clinical and immunological manifestations.Unlike what occurs in the multibacillary form,the diagnostic tests for the paucibacillary form are nonspecific and not very sensitive,allowing the existence of infected individuals without treatment,which contributes to the spread of the pathogen in the population.To mitigate this contamination,more sensitive diagnostic tests capable of detecting paucibacillary patients are needed.AIM To predict the three-dimensional structure models of M.leprae antigens with serodiagnostic potential for leprosy.METHODS In this in silico study,satisfactory templates were selected in the Protein Data Bank(PDB)using Basic Local Alignment Search Tool to predict the structural templates of ML2038,ML0286,ML0050,and 85B antigens by comparative modeling.The templates were selected according to general criteria such as sequence identity,coverage,X-ray resolution,Global Model Quality Estimate value and phylogenetic relationship;Clustal X 2.1 software was used in this analysis.Molecular modeling was completed using the software Modeller 9v13.Visualization of the models was made using ViewerLite 4.2 and PyMol software,and analysis of the quality of the predicted models was performed using the QMEAN score and Z-score.Finally,the three-dimensional moels were validated using the MolProbity and Verify 3D platforms.RESULTS The three-dimensional structure models of ML2038,ML0286,ML0050,and 85B antigens of M.leprae were predicted using the templates PDB:3UOI(90.51%identity),PDB:3EKL(87.46%identity),PDB:3FAV(40.00%identity),and PDB:1F0N(85.21%identity),respectively.The QMEAN and Z-score values indicated the good quality of the structure models.These data refer to the monomeric units of antigens,since some of these antigens have quaternary structure.The validation of the models was performed with the final three-dimensional structure-monomer(ML0050 and 85B antigens)and quaternary structures(ML2038 and ML0286).The majority of amino acid residues were observed in favorable and allowed regions in the Ramachandran plot,indicating correct positioning of the side chain and absence of steric impediment.The MolProbity score value and Verify 3D results of all models indicated a satisfactory prediction.CONCLUSION The polarized immune response against M.leprae creates a problem in leprosy detection.The selection of immunodominant epitopes is essential for the development of more sensitive serodiagnostic tests,for this it is important to know the three-dimensional structure of the antigens,which can be predicted with bioinformatics tools.
文摘Leprosy is characterized by skin lesions and peripheral nerve damage. It may take a long time before the diagnosis can be confirmed if the patients have no typical skin involvements. Here we report an unusual case. A 40-year-old male with lepromatous leprosy showed a gradual onset of bilateral symmetrical neuropathies without characteristic skin manifestations seven years after onset and with pulmonary tuberculosis simultaneously. He was misdiagnosed as having Guillani-Barr6 syndrome and systemic necrotizing vasculitis for 10 years until the skin biopsy was performed. This case indicates that the risk of leprosy exists, though new cases being detected have significantly declined over the last 50 years; neurologists need to pay more attention to leprosy with various manifestations .
基金supported by grants from the Academic Promotion Programme of Shandong First Medical University(2019LJ002)National Natural Science Foundation of China(82103734)+1 种基金the Shandong Province Taishan Scholar Project(tsqn202211346)the China Postdoctoral Science Foundation(2023M732128),and Shandong Postdoctoral Science Foundation(SDCX-ZG-202301007).
文摘Leprosy,a disease caused by Mycobacterium leprae,can destroy susceptible individuals’skin and peripheral nerves,ultimately leading to disfigurement.Due to its symptoms,it has been stigmatized since ancient times.As recently as the 1950s,there were nearly 400,000 leprosy patients in China.
基金supported by the Biogeography,Diversity and Conservation Lab of the University of Malaga,Project PID2021-124063OB-I00 of the Spanish Ministry of Science and Innovation and European Regional Development Fund(ERDF)and by the Leprosy Research Initiative Foundation(Grant#FP25\19)supported by a postdoctoral contract of the Plan Propio de Investigacion,Transferencia y Divulgacion Cientifica of the University of Malaga+7 种基金supported by MOPGA:Visiting Fellowship Program for early career researchers,Campus France,Francesupported by Gordon and Betty Moore Foundation through grant GBMF9258 to the Comunidad de Manejo de Fauna Silvestre en la Amazonia y en Latinoamerica(COMFAUNA)supported UK Research and Innovation’s Global Challenges Research Fund(UKRI GCRF)Trade,Development and the Environment Hub project(ES/S008160/1)supported by the joint NSF-NIH-NIFA Ecology and Evolution of Infectious Disease program(DEB#1911457)benefited from an‘Investissement d’Avenir’Grant managed by Agence Nationale de la Recherche,France(LABEX CEBA:ANR-10-LABX-25-01)supported by Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior—Brasil(CAPES)for a PNPD research fellowship.(88887.717863/2022-00)supported by a Conselho Nacional de Desenvolvimento Cientifico e Tecnologico(CNPq)postdoctoral fellowship(150261/2023-3)supported by the Sustainable Landscapes and Livelihoods Programme.
文摘Background Leprosy remains a persistent public health challenge,where human-to-human transmission of Mycobacterium leprae via respiratory droplets is well established.In the tropical Americas,growing evidence implicates armadillos as important zoonotic reservoirs,particularly through direct contact during hunting and handling.However,such transmission has so far been considered rare and highly localised.This study provides a comprehensive spatial analysis of the role of armadillo hunting in human leprosy transmission,quantifying its contribution to disease prevalence and identifying geographic hotspots where interventions could be most effective.Methods Using Brazil’s 326,001 reported leprosy cases from 2013 to 2022,we applied a pathogeographical approach to explore transmission dynamics.We compiled data on 554 hunted armadillos across 175 municipalities and M.leprae prevalence in 376 armadillo individuals from 97 municipalities(mean prevalence=38.5%).These were used to build spatial models assessing hunting-related infection risk and integrated as a variable into a generalised linear model alongside socioeconomic,climatic,and environmental predictors to evaluate their effects on human leprosy prevalence.Results Key predictors of armadillo hunting included higher population density(P<0.001)and firearm availability(P<0.01).Infection in armadillos was negatively correlated with native habitat coverage(coefficient:−2.28;P<0.001),suggesting that environmental degradation can amplify infection risk.The armadillo-hunting infection risk variable—generated by combining armadillo hunting and infection favourability models—emerged as the second strongest predictor of human leprosy prevalence(coefficient:1.69;P<0.001),accounting for~25%of cases nationally and around 40%in deforestation hotspots.Additional positive predictors included greater precipitation seasonality(coefficient:0.82;P<0.001)and malnutrition(coefficient:0.01;P<0.001),while higher population density(coefficient:−0.64;P<0.001),natural habitat coverage(coefficient:−0.50;P<0.001)and socioeconomic status(coefficient:−0.47;P=0.013)were linked to reduced disease prevalence.Conclusions Armadillo hunting seems to play a more significant role in human leprosy transmission than previously recognised.To address this overlooked pathway,targeted interventions should focus on reducing unsafe and illegal hunting,improving communication around zoonotic risks,strengthening disease surveillance in high-risk areas,and conducting genetic studies to confirm wildlife-to-human transmission.Our findings highlight the importance of incorporating wildlife-associated transmission pathways into strategies to reduce disease prevalence and mitigate future outbreaks in tropical regions facing rapid environmental change and persistent poverty.
基金supported by the Natural Science Foundation of Hunan Province,China(No.2018JJ6010).
文摘Introduction:Type II lepra reaction(T2LR)is a rare immune-mediated complication in patients with leprosy and is typically treated with glucocorticoids and thalidomide.Idiopathic intracranial hypertension(IIH)is marked by increased intracranial pressure leading to symptoms like headache and vision loss.Here,we report a rare case of concomitant T2LR and IIH.Case presentation:A 35-year-old woman with leprosy had been treated with corticosteroids and thalidomide for T2LR over a period of 2 years.She subsequently experienced progressive vision loss,which was initially misdiagnosed as optic neuritis.After high-dose glucocorticoid treatment,her condition worsened.The patient was later found to have elevated intracranial pressure and was ultimately diagnosed with IIH.She was treated with cerebrospinal fluid diversion,which relieved her symptoms.The patient was mildly obese and had received high-dose corticosteroids.T2LR is associated with increased proinflammatory cytokine levels,so the IIH condition was speculated to be related to T2LR.Discussion:Evidence suggests that inflammatory mediators in T2LR may increase choroid plexus permeability,raising intracranial pressure.Long-term glucocorticoid use is associated with IIH,as it may increase intracranial pressure through local cortisol activation in the choroid plexus.The patient’s misdiagnosis of optic neuritis,due to a lack of typical IIH symptoms,delayed appropriate treatment and led to vision loss.Conclusion:While this case may represent an extreme instance as T2LR and IIH are both rare conditions,it highlights a broader issue:prolonged steroid use can increase intracranial pressure to varying degrees,however not all patients with elevated intracranial pressure experience headaches.This case emphasizes the importance of considering IIH in patients on chronic corticosteroids treatment presenting with unusual vision changes.Clinicians should be aware of this possibility and conduct thorough evaluations for high risk populations to detect such complications.
基金This study received financial support from the Conselho de Desenvolvimento Tecnológico e Científico/CNPq/BRAZIL,DECIT 2008,DECIT 2012,FAPEMIG,TC 304/2013/FNS/MS and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior(CAPES).OAMF received PQ fellowships from CNPq.These fundings sources had no role in the design of the study and collection,analysis,implementation,and interpretation of data and in writing the manuscript.
文摘Background: Leprosy is a chronic infectious disease classified into two subgroups for therapeutic purposes:paucibacillary(PB)and multibacillary(MB),closely related to the host immune responses.In this context it is noteworthy looking for immunological biomarkers applicable as complementary diagnostic tools as well as a laboratorial strategy to follow-up leprosy household contacts.Methods:: The cross-sectional study enrolled 49 participants,including 19 patients and 30 healthy controls.Peripheral blood mononuclear cells(PBMC)were isolated and incubated in the presence of Mycobacterium leprae bacilli.The cells were prepared for surface(CD4+and CD8+)and intracytoplasmic cytokine staining(IFN-γ,IL-4 and IL-10).Multiple comparisons amongst groups were carried out by ANOVA,Kruskal–Wallis,Student T or Mann–Whitney test.Comparative analysis of categorical variables was performed by Chi-square.Functional biomarker signature analysis was conducted using the global median values for each biomarker index as the cut-off edge to identify the proportion of subjects with high biomarker levels.Results: The cytokine signature analysis demonstrated that leprosy patients presented a polyfunctional profile of T-cells subsets,with increased frequency of IFN-γ+T-cell subsets along with IL-10+and IL-4+from CD4+T-cells,as compared to health Controls(Venn diagram report).Moreover,statistical analysis was carried out using parametric or non-parametric variance analysis followed by pairwise multiple comparisons,according to the data normality distribution.L(PB)displayed a polyfunctional profile characterized by enhanced percentage of IFN-γ+,IL-10+and IL-4+produced by most T-cell subsets,as compared to L(MB)that presented a more restricted cytokine functional profile mediated by IL-10+and IL-4+T-cells with minor contribution of IFN-γproduced by CD4+T-cells.Noteworthy was that HHC(MB)exhibited enhanced frequency of IFN-γ+T-cells,contrasting with HHC(PB)that presented a cytokine profile limited to IL-10 and IL-4.Conclusions: Our data demonstrated that L(PB)displayed enhanced percentage of IFN-γ+,IL-10+and IL-4+as compared to L(MB)that presented functional profile mediated by IL-10+and IL-4+T-cells and HHC(MB)exhibited enhanced frequency of IFN-γ+T-cells,contrasting with HHC(PB).Together,our findings provide additional immunological features associated with leprosy and household contacts.These data provide evidence that biomarkers of immune response can be useful complementary diagnostic/prognostic tools as well as insights that household contacts should be monitored to access putative subclinical infection.
基金supported by Academic promotion programme of Shandong First Medical University(2019LJ002)the Natural Science Foundation of Shandong Province(ZR2023MH046)+1 种基金National Natural Science Foundation of China(82173430,82230107,82273545)the Innovation Project of Shandong Academy of Medical Sciences.
文摘Leprosy is an infectious granulomatous disease caused by Mycobacterium leprae that affects the skin and can lead to deformity by damaging peripheral nerves.Although leprosy is no longer an incurable disease,its epidemic has not been well controlled because of its unclear routes of transmission and the lack of an effective vaccine.Moreover,leprosy has long been an ideal disease model for the study of genetics and immunology of infectious diseases due to its strong genetic predisposition and immune-dependent spectrum of clinical manifestations.Here,we review the latest and important findings of the pathogenesis of leprosy.Recent studies have shown that the highly conserved M.leprae is zoonotic,which further complicates the ambiguous transmission of M.leprae.Genetically,genome-wide association studies of leprosy have reported dozens of susceptibility genes,most of which are immune-related,and thus systematically elucidate the immunogenetic basis of the disease.Immunologically,plenty of novel mechanisms of host defense against intracellular bacterial infection and the modulation of host immunity by M.leprae have been depicted.Despite these great achievements,there are still gaps between pathogenic biology,genetics,and immunology of leprosy,limiting our in-depth understanding of leprosy pathogenesis.Further efforts,such as multi-omics data integration and the development of viable animal models for immunogenetic studies are urgently needed to accelerate advances in the precise prevention and treatment of leprosy.
文摘Background: Leprosy control achieved dramatic success in the 1980s–1990s with the implementation of short course multidrug therapy,which reduced the global prevalence of leprosy to less than 1 in 10000 population.However,a period of relative stagnation in leprosy control followed this achievement,and only limited further declines in the global number of new cases reported have been achieved over the past decade.Main text In 2016,major stakeholders called for the development of an innovative and comprehensive leprosy strategy aimed at reducing the incidence of leprosy,lowering the burden of disability and discrimination,and interrupting transmission.This led to the establishment of the Global Partnership for Zero Leprosy(GPZL)in 2018,with partners aligned around a shared Action Framework committed to achieving the WHO targets by 2030 through national leprosy program capacity-building,resource mobilisation and an enabling research agenda.GPZL convened over 140 experts from more than 20 countries to develop a research agenda to achieve zero leprosy.The result is a detailed research agenda focusing on diagnostics,mapping,digital technology and innovation,disability,epidemiological modelling and investment case,implementation research,stigma,post exposure prophylaxis and transmission,and vaccines.This research agenda is aligned with the research priorities identified by other stakeholders.Conclusions: Developing and achieving consensus on the research agenda for zero leprosy is a significant step forward for the leprosy community.In a next step,research programmes must be developed,with individual components of the research agenda requiring distinct expertise,varying in resource needs,and operating over different timescales.Moving toward zero leprosy now requires partner alignment and new investments at all stages of the research process,from discovery to implementation.
基金The authors thankfully acknowledge the assistance of Mr. Sultan Md Elias Uddin. Program Manager, Leprosy control project, Chittagong.
文摘Objective:This study was performed to compare the efficacy and safety of methotrexate(MTX)plus prednisolone versus prednisolone monotherapy in patients with erythema nodosum leprosum(ENL).Methods:This comparative clinical study was performed in the Chittagong Medical College Hospital,Bangladesh from June 2018 to December 2019.Nineteen patients were selected according to inclusion criteria and randomly allocated to either the MTX plus prednisolone group(Group A,n=10)or the prednisolone monotherapy group(Group B,n=9).All patients were followed up until the end of the 6-month duration of therapy to observe the clinical outcomes and adverse effects.Results:All patients in both groups showed significant improvement(P=0.005 and P=0.008 in Group A and B,respectively).However,prednisolone-related adverse events were more frequent in Group B.Conclusion:The present study has demonstrated that a combination of prednisolone and MTX is a safer and more effective treatment than steroid monotherapy in ENL patients including the healing of nodules.However,this combination therapy did not appear to have a significant steroid-sparing effect,possibly because of the small sample size and short study period.Therefore,a well-designed multicenter randomized controlled trial is recommended for validation of MTX with prednisolone for the management of ENL.
