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Frontiers in Immunology 2021It was previously published that single-nucleotide polymorphism rs2476601 ( [protein tyrosine phosphatase non-receptor type 22]-C1858T) might be related to increased... (Meta-Analysis)
Meta-Analysis
It was previously published that single-nucleotide polymorphism rs2476601 ( [protein tyrosine phosphatase non-receptor type 22]-C1858T) might be related to increased sensibility to and infection. However, the results were inconclusive despite a high degree of similarity between both parameters. Herein, we carried out this meta-analysis to systematically summarize and articulate the correlation between -C1858T polymorphism and mycobacterial infection. The susceptibility of -C1858T carriers with autoimmune conditions receiving immunosuppressive therapy to and infection was determined. A systematic retrieval of studies on relevance of -C1858T polymorphism to susceptibility of or infection was performed in Chinese National Knowledge Infrastructure, PubMed and Embase databases. We regarded Odds ratios (ORs) and 95% confidence intervals (CIs) as the determined effect size. Finally, four and two case-control studies on tuberculosis and leprosy, respectively, were included. In all genetic models, without indicated association between -C1858T polymorphism and tuberculosis's susceptibility. [C versus T: OR = 0.22 (95% CI: 0.09-0.50, P = 0.887); CT versus CC: OR = 0.21 (95% CI: 0.09-0.49, P = 0.889); TT+CT versus CC: OR = 0.21 (95% CI: 0.09-0.49, P = 0.889)]. A significantly increased risk of leprosy was perceived in patients with the -C1858T polymorphism [C versus T: OR = 2.82 (95% CI: 1.02-7.81, P = 0.108)]. While the -C1858T polymorphism is irrelevant to higher susceptibility to the infection of in Caucasians and Asians, it is relevant to increased susceptibility to the infection of . However, the results of are supposed to interpreted with prudence owing to the limited quantity of studies and heterogeneity. Further well-designed studies with sufficient populations are required to verify our conclusions.
Topics: Alleles; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Leprosy; Mycobacterium leprae; Mycobacterium tuberculosis; Odds Ratio; Polymorphism, Single Nucleotide; Protein Tyrosine Phosphatase, Non-Receptor Type 22; Publication Bias; Risk; Tuberculosis
PubMed: 33717071
DOI: 10.3389/fimmu.2021.592841 -
Mediators of Inflammation 2015Reactional episodes in leprosy are a result of complex interactions between the immune system, Mycobacterium leprae, and predisposing factors, including dental... (Review)
Review
Reactional episodes in leprosy are a result of complex interactions between the immune system, Mycobacterium leprae, and predisposing factors, including dental infections. To determine the main inflammatory mediators in the immunopathological process of dental infections and leprosy reactions, we conducted a systematic review of primary literature published between 1996 and 2013. A three-stage literature search was performed (Stage I, "leprosy reactions" and "inflammatory mediators"; Stage II, "dental infections" and "inflammatory mediators"; and Stage III, "leprosy reactions," "dental infections," and "inflammatory mediators"). Of the 911 eligible publications, 10 were selected in Stage I, 68 in Stage II, and 1 in Stage III. Of the 27 studied inflammatory mediators, the main proinflammatory mediators were IL-6, IFN-γ, TNF-α, IL-1β, and IL-17; the main anti-inflammatory mediators were IL-10 and IL-4. Serum IL-6 and TNF-α concentrations were significant during periodontal and reactional lesion evolution; IFN-γ and IL-1β were associated with types 1 and 2 reactions and chronic periodontal disease. The proinflammatory mediators in dental infections and leprosy reactions, especially IL-6 and TNF-α, were similar across studies, regardless of the laboratory technique and sample type. IFN-γ and IL-1β were significant for leprosy reactions and periodontal diseases. This pattern was maintained in serum.
Topics: Animals; Cytokines; Humans; Interferon-gamma; Leprosy; Stomatognathic Diseases; Tumor Necrosis Factor-alpha
PubMed: 26339136
DOI: 10.1155/2015/548540 -
PLoS Neglected Tropical Diseases Sep 2021Leprosy is a chronic infectious disease caused by Mycobacterium leprae, the annual new case detection in 2019 was 202,189 globally. Measuring endemicity levels and...
BACKGROUND
Leprosy is a chronic infectious disease caused by Mycobacterium leprae, the annual new case detection in 2019 was 202,189 globally. Measuring endemicity levels and burden in leprosy lacks a uniform approach. As a result, the assessment of leprosy endemicity or burden are not comparable over time and across countries and regions. This can make program planning and evaluation difficult. This study aims to identify relevant metrics and methods for measuring and classifying leprosy endemicity and burden at (sub)national level.
METHODS
We used a mixed-method approach combining findings from a systematic literature review and a Delphi survey. The literature search was conducted in seven databases, searching for endemicity, burden and leprosy. We reviewed the available evidence on the usage of indicators, classification levels, and scoring methods to measure and classify endemicity and burden. A two round Delphi survey was conducted to ask experts to rank and weigh indicators, classification levels, and scoring methods.
RESULTS
The literature review showed variation of indicators, levels, and cut-off values to measure leprosy endemicity and/or burden. The most used indicators for endemicity include new case detection rate (NCDR), new cases among children and new cases with grade 2 disability. For burden these include NCDR, MB cases, and prevalence. The classification levels 'high' and 'low' were most important. It was considered most relevant to use separate scoring methods for endemicity and burden. The scores would be derived by use of multiple indicators.
CONCLUSION
There is great variation in the existing method for measuring endemicity and burden across countries and regions. Our findings contribute to establishing a standardized uniform approach to measure and classify leprosy endemicity and burden at (sub)national level, which would allow effective communication and planning of intervention strategies.
Topics: Cost of Illness; Delphi Technique; Endemic Diseases; Global Health; Humans; Leprosy
PubMed: 34543282
DOI: 10.1371/journal.pntd.0009769 -
PLoS Neglected Tropical Diseases May 2021Leprosy is an infectious disease caused by Mycobacterium leprae. As incidence begins to decline, the characteristics of new cases shifts away from those observed in...
BACKGROUND
Leprosy is an infectious disease caused by Mycobacterium leprae. As incidence begins to decline, the characteristics of new cases shifts away from those observed in highly endemic areas, revealing potentially important insights into possible ongoing sources of transmission. We aimed to investigate whether transmission is driven mainly by undiagnosed and untreated new leprosy cases in the community, or by incompletely treated or relapsing cases.
METHODOLOGY/PRINCIPAL FINDINGS
A literature search of major electronic databases was conducted in January, 2020 with 134 articles retained out of a total 4318 records identified (PROSPERO ID: CRD42020178923). We presented quantitative data from leprosy case records with supporting evidence describing the decline in incidence across several contexts. BCG vaccination, active case finding, adherence to multidrug therapy and continued surveillance following treatment were the main strategies shared by countries who achieved a substantial reduction in incidence. From 3950 leprosy case records collected across 22 low endemic countries, 48.3% were suspected to be imported, originating from transmission outside of the country. Most cases were multibacillary (64.4%) and regularly confirmed through skin biopsy, with 122 cases of suspected relapse from previous leprosy treatment. Family history was reported in 18.7% of cases, while other suspected sources included travel to high endemic areas and direct contact with armadillos. None of the countries included in the analysis reported a distinct increase in leprosy incidence in recent years.
CONCLUSIONS/SIGNIFICANCE
Together with socioeconomic improvement over time, several successful leprosy control programmes have been implemented in recent decades that led to a substantial decline in incidence. Most cases described in these contexts were multibacillary and numerous cases of suspected relapse were reported. Despite these observations, there was no indication that these cases led to a rise in new secondary cases, suggesting that they do not represent a large ongoing source of human-to-human transmission.
Topics: Animals; Armadillos; BCG Vaccine; Drug Therapy, Combination; Humans; Leprostatic Agents; Leprosy; Mycobacterium leprae; Recurrence; Travel
PubMed: 34038422
DOI: 10.1371/journal.pntd.0009436 -
PLoS Neglected Tropical Diseases Aug 2021Leprosy elimination primarily targets transmission of Mycobacterium leprae which is not restricted to patients' households. As interruption of transmission is imminent...
BACKGROUND
Leprosy elimination primarily targets transmission of Mycobacterium leprae which is not restricted to patients' households. As interruption of transmission is imminent in many countries, a test to detect infected asymptomatic individuals who can perpetuate transmission is required. Antibodies directed against M. leprae antigens are indicative of M. leprae infection but cannot discriminate between active and past infection. Seroprevalence in young children, however, reflects recent M. leprae infection and may thus be used to monitor transmission in an area. Therefore, this literature review aimed to evaluate what has been reported on serological tests measuring anti-M. leprae antibodies in children without leprosy below the age of 15 in leprosy-endemic areas.
METHODS AND FINDINGS
A literature search was performed in the databases Pubmed, Infolep, Web of Science and The Virtual Health Library. From the 724 articles identified through the search criteria, 28 full-text articles fulfilled all inclusion criteria. Two additional papers were identified through snowballing, resulting in a total of 30 articles reporting data from ten countries. All serological tests measured antibodies against phenolic glycolipid-I or synthetic derivatives thereof, either quantitatively (ELISA or UCP-LFA) or qualitatively (ML-flow or NDO-LID rapid test). The median seroprevalence in children in endemic areas was 14.9% and was stable over time if disease incidence remained unchanged. Importantly, seroprevalence decreased with age, indicating that children are a suitable group for sensitive assessment of recent M. leprae infection. However, direct comparison between areas, solely based on the data reported in these studies, was impeded by the use of different tests and variable cut-off levels.
CONCLUSIONS
Quantitative anti-PGL-I serology in young children holds promise as a screening test to assess M. leprae infection and may be applied as a proxy for transmission and thereby as a means to monitor the effect of (prophylactic) interventions on the route to leprosy elimination.
Topics: Antibodies, Bacterial; Antigens, Bacterial; Child; Child, Preschool; Contact Tracing; Endemic Diseases; Family Characteristics; Humans; Leprosy; Mycobacterium leprae
PubMed: 34449763
DOI: 10.1371/journal.pntd.0009667 -
Clinical Microbiology and Infection :... Dec 2021Vaccination and single-dose rifampin are the main proven effective intervention types for preventing leprosy among contacts of Mycobacterium leprae endemic areas.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vaccination and single-dose rifampin are the main proven effective intervention types for preventing leprosy among contacts of Mycobacterium leprae endemic areas. Currently, no high-quality evidence is available regarding the best prophylactic intervention.
OBJECTIVES
Our primary study aim is to detect the most effective prophylactic intervention for the prevention of leprosy.
METHODS
In May 2019, 12 databases were searched systematically. Updated search terms were developed in March 2020 to complete an updated search. All randomized controlled trials (RCTs) comparing the different types of chemoprophylactic and immunoprophylactic interventions in leprosy prevention were included. Our participants were contacts of patients with leprosy or people residing in leprosy endemic communities. We searched for different types of chemoprophylactic and immunoprophylactic interventions used in leprosy prevention. We used network meta-analysis and meta-analysis. Quality assessment was performed using Cochrane Risk of Bias for included RCTs, in which all included RCTs were rated to be low to moderate risk. We registered our protocol in Prospero with ID CRD42019143207.
RESULTS
Among 11 included studies (326 264 patients) from original and updated search terms, eight were eligible for network meta-analysis (NMA) while four were eligible for MA. Findings suggest that Bacillus Calmette-Guérin (BCG) vaccination was the most effective intervention compared to placebo (risk ratios (RRs) 0.49 (0.30, 0.80), p 0.77), followed by combined BCG vaccination and single-dose rifampicin (SDR) with similarly low values (RR 48%, p 0.77). BCG revaccination was the least effective intervention compared to placebo (RR 1.08 (0.36, 3.22), p 0.26).
CONCLUSION
Compared to placebo, the BCG vaccine was the most effective prophylactic intervention. The combination of BCG vaccination + SDR had nearly the same efficacy as BCG vaccination alone, while BCG revaccination was the least effective. Thus, vaccination proved to be a more effective treatment than SDR alone. A well-designed multicenter RCT is warranted to evaluate the safety of these vaccines.
Topics: BCG Vaccine; Chemoprevention; Humans; Leprosy; Network Meta-Analysis; Randomized Controlled Trials as Topic; Rifampin
PubMed: 34332107
DOI: 10.1016/j.cmi.2021.07.032 -
Journal of Global Antimicrobial... Sep 2022Dapsone is one of the important drugs in the treatment of leprosy. The present study aims to evaluate the resistance of Mycobacterium leprae isolates to dapsone, in turn... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Dapsone is one of the important drugs in the treatment of leprosy. The present study aims to evaluate the resistance of Mycobacterium leprae isolates to dapsone, in turn assisting in implementing better control strategies for leprosy elimination.
METHODS
A systematic literature search was conducted in PubMed, Embase, Medline, and Web of Science. Two independent reviewers selected the literature according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), extracted data, and evaluated the risk of bias. Drug resistance data were pooled using the random-effects model. Subgroup analysis was performed based on across sampling time, region, study population (treatment status, relapses status), and sample size.
RESULTS
A total of 30 studies were included. The results of meta-analysis showed that the dapsone resistance rate of leprosy patients after treatment was 8% (95% confidence interval [CI], 6%-10%). Compared to the rates of primary resistance of new cases without treatment therapy (pooled incidence, 4% [95% CI, 2%-5%]), treatment cases (13% [95% CI 9%-16%]) had secondary resistance, and relapse cases (26% [95% CI, 18%-33%]) had drug resistance. In addition, the drug resistance rate of monotherapy was significantly increased than that of relapsed patients treated with diamino-diphenylsulfone monotherapy. Subgroup analysis showed that the patients in the Western Pacific have the highest dapsone resistance, and the resistance to dapsone was slightly lower after 2005. For sample size, the rate in the group under 100 samples was significantly higher than in the other.
CONCLUSION
Dapsone resistance is closely related to leprosy relapse and long-term drug use. Dapsone monotherapy is one of important reasons for drug resistance in relapsed cases. Drug resistance varies among different populations and regions of the world.
Topics: Dapsone; Humans; Leprosy; Mycobacterium leprae; Recurrence; Risk Factors
PubMed: 35643395
DOI: 10.1016/j.jgar.2022.05.015 -
The American Journal of Tropical... May 2017AbstractDapsone is a bactericidal and bacteriostatic against , a causative agent of leprosy. Dapsone is also applied in a range of medical fields because of its... (Review)
Review
AbstractDapsone is a bactericidal and bacteriostatic against , a causative agent of leprosy. Dapsone is also applied in a range of medical fields because of its anti-inflammatory and immunomodulatory effects. Dapsone hypersensitivity syndrome (DHS) is a rare yet serious adverse drug reaction (ADR) caused by dapsone involving multiple organs. We performed a systematic review of published articles describing dapsone-induced hypersensitivity syndrome, including all Chinese articles and the latest literature available in online databases published between October 2009 and October 2015. We determined the prevalence, clinical characteristics, and mortality rate of DHS. Importantly, we also summarized the recent advances in genetic testing allowing prediction of ADRs. In an initial systematic electronic search, we retrieved 191 articles. Subsequently, these articles were further filtered and ultimately 84 articles (60 Chinese case reports, 21 non-Chinese articles, and three epidemiological studies) were selected, which included 877 patients. The prevalence of DHS among Chinese patients was 1.5% with a fatality rate of 9.6%. Early withdrawal of dapsone and appropriate treatment reduced the fatality rate. Most importantly, genetic screening for the HLA-B*13:01 allele among high-risk populations showed a significant utility as a useful genetic marker to DHS. In conclusion, this review discusses the epidemiological and clinical characteristics of DHS among Chinese patients, which may help physicians to understand this syndrome.
Topics: Adolescent; Adult; Aged; Alleles; Child; China; Dapsone; Drug Hypersensitivity; Drug Substitution; Female; Genetic Testing; HLA-B13 Antigen; Humans; Leprostatic Agents; Leprosy; Male; Middle Aged; Mycobacterium leprae; Prevalence; Primary Prevention; Survival Analysis; Syndrome
PubMed: 28167593
DOI: 10.4269/ajtmh.16-0628 -
Journal of Infection and Public Health Aug 2020The aim of this systematic review was to investigate the studies that evaluated the sensitivity and specificity of serologic tests using recombinant protein antigens...
The aim of this systematic review was to investigate the studies that evaluated the sensitivity and specificity of serologic tests using recombinant protein antigens from Mycobacterium leprae for leprosy diagnosis. We included 13 studies that were available in PubMed, Brazilian Virtual Library of Health, Web of Science, ScienceDirect and Scopus. From these studies, we found that the recombinant serine-rich 45-kDa protein of M. leprae (ML0411) demonstrated high performance for multibacillary (MB) also to paucibacillary (PB) patients, although this study was tested only for Indian population. Despite that, studies using the ND-O-LID antigen have been able to more accurately identify new cases of leprosy among people living in endemic or non-endemic areas and household contacts in Brazil, Colombia, and the Philippines, especially when combined with other biomarkers. Finally, low sensitivity values for PB patients' antibodies response remain challenging for tests intended to diagnose clinical forms that comprise this classification in leprosy.
Topics: Antibodies, Bacterial; Antigens, Bacterial; Brazil; Colombia; Humans; Leprosy; Mycobacterium leprae; Philippines; Recombinant Proteins; Reproducibility of Results; Serologic Tests
PubMed: 32299687
DOI: 10.1016/j.jiph.2019.12.011 -
Revista Brasileira de Epidemiologia =... 2021To investigate the risk factors associated with leprosy in contacts of patients. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To investigate the risk factors associated with leprosy in contacts of patients.
METHOD
We carried out a systematic review and meta-analysis by searching the databases MEDLINE, Embase, Cochrane Library, CINAHL, LILACS, Scopus, and Web of Science until September 2019. Four reviewers carried out the selection, analysis, and evaluation of quality of studies. The random effects model was used to calculate the pooled relative risk (RR) and 95% confidence intervals (95% CI) when heterogeneity was greater than 50%.
RESULTS
The search resulted in 2,148 references and included 24 reports. Most of the studies had been conducted in Brazil and India, had a cohort design and included household, neighbors, and social contacts. The risk factors associated with illness due to leprosy in contacts were: illiteracy (RR = 1,48; 95%CI 1,22 - 1,79), living in the same house (RR = 2,41; 95%CI 1,87 - 3,10) of a case of leprosy with high bacillary load (RR = 2.40; 95%CI 1.69 - 3.41), seropositivity to the Mycobacterium leprae PGL-1 (phenolic glycolipid-1) antigen (RR = 3.54; 95%CI 2.21 - 5.67), presence of the bacillus in the bloodstream (RR = 10.61; 95%CI 4.74 - 23.77) and negative Mitsuda reaction (RR = 2,68; 95%CI 1,76 - 4,07). Immunization with BCG (bacillus Calmette-Guérin) vaccine had a protective effect against leprosy.
CONCLUSION
Leprosy in contacts of patients involves social determination, individual susceptibility, and difficulties in access to disease control actions, but modifiable risk factors are the main determinants of illness in this population.
Topics: Antigens, Bacterial; Brazil; Glycolipids; Humans; Leprosy; Mycobacterium leprae
PubMed: 34231829
DOI: 10.1590/1980-549720210039