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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 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 -
Clinical Microbiology and Infection :... Nov 2021The fact that Mycobacterium leprae does not grow in vitro remains a challenge in the survey of its antimicrobial resistance (AMR). Mainly molecular methods are used to... (Review)
Review
BACKGROUND
The fact that Mycobacterium leprae does not grow in vitro remains a challenge in the survey of its antimicrobial resistance (AMR). Mainly molecular methods are used to diagnose AMR in M. leprae to provide reliable data concerning mutations and their impact. Fluoroquinolones (FQs) are efficient for the treatment of leprosy and the main second-line drugs in case of multidrug resistance.
OBJECTIVES
This study aimed at performing a systematic review (a) to characterize all DNA gyrase gene mutations described in clinical isolates of M. leprae, (b) to distinguish between those associated with FQ resistance or susceptibility and (c) to delineate a consensus numbering system for M. leprae GyrA and GyrB.
DATA SOURCES
Data source was PubMed.
STUDY ELIGIBILITY CRITERIA
Publications reporting genotypic susceptibility-testing methods and gyrase gene mutations in M. leprae clinical strains.
RESULTS
In 25 studies meeting our inclusion criteria, 2884 M. leprae isolates were analysed (2236 for gyrA only (77%) and 755 for both gyrA and gyrB (26%)): 3.8% of isolates had gyrA mutations (n = 110), mostly at position 91 (n = 75, 68%) and 0.8% gyrB mutations (n = 6). Since we found discrepancies regarding the location of substitutions associated with FQ resistance, we established a consensus numbering system to properly number the mutations. We also designed a 3D model of the M. leprae DNA gyrase to predict the impact of mutations whose role in FQ-susceptibility has not been demonstrated previously.
CONCLUSIONS
Mutations in DNA gyrase are observed in 4% of the M. leprae clinical isolates. To solve discrepancies among publications and to distinguish between mutations associated with FQ resistance or susceptibility, the consensus numbering system we proposed as well as the 3D model of the M. leprae gyrase for the evaluation of the impact of unknown mutations in FQ resistance, will provide help for resistance surveillance.
Topics: DNA Gyrase; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Microbial Sensitivity Tests; Mutation; Mycobacterium leprae
PubMed: 34265461
DOI: 10.1016/j.cmi.2021.07.007 -
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 -
Infection, Genetics and Evolution :... Sep 2021Leprosy is an infectious disease that may present different clinical forms depending on host immune response to Mycobacterium leprae. Mannose-binding lectin (MBL) is an...
Leprosy is an infectious disease that may present different clinical forms depending on host immune response to Mycobacterium leprae. Mannose-binding lectin (MBL) is an acute phase protein associated with the pathophysiology of leprosy. Some studies have shown that there is a correlation between serum levels of MBL and polymorphisms in its gene associated with susceptibility per se and to different clinical forms. The aim of this study was to conduct a systematic review of publications in the literature that studied the association of MBL with leprosy. Databases were searched until December 2020 (PROSPERO: CRD42020158458), and additional searches were conducted scanning the reference lists of the articles. Two independent reviewers assessed the study quality using the Newcastle-Ottawa Quality Assessment Scale. Finally, 10 eligible articles were included in the study. The overall results indicated that both low MBL serum levels and polymorphisms in the structural or promoter region of its gene seem to be associated as protective factors against the development of severe forms. The results suggest that MBL may play a role in the clinical progression of leprosy.
Topics: Bacterial Proteins; Humans; Leprosy; Mannose-Binding Lectin; Mycobacterium leprae
PubMed: 34052419
DOI: 10.1016/j.meegid.2021.104945 -
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 -
Medicina Clinica Feb 2022The aim of this article is to summarize published information on systemic infective complications of tattoos to gain an update of the current picture.
INTRODUCTION
The aim of this article is to summarize published information on systemic infective complications of tattoos to gain an update of the current picture.
METHODS
A literature search was performed in PubMed database (2009-2019), and compared with a search without year restriction. Eligibility criteria were studies on systemic tattoo-related infections, including case reports, case series, outbreak investigations, reviews, and systematic reviews.
RESULTS
We identified 17 manuscripts with systemic infections between 2009 and 2019, with one reported fatality. In contrast to the historical records, no reports of systemic tuberculosis, syphilis or viral (hepatitis or HIV) infections were reported within the study period. A few sporadic cases or Mycobacterium leprae (India) or regional lymphadenopathy associated with skin lesions in non-tuberculosis mycobacteria were identified. Persistent fever with rigour was common in bacterial bloodstream infections. One episode of staphylococcal toxic shock syndrome and several episodes of septic shock were reported, associated with cellulitis or necrotizing fasciitis within two weeks of the procedure, predominantly caused by pyogenic bacteria (S. aureus or streptococcus). Identification of lung or systemic embolisms in the absence of local symptoms, was indicative of (right or left) infective endocarditis.
CONCLUSIONS
Bacterial bloodstream infections should be considered in subjects developing fever and rigour after tattoos, regardless of local symptoms. A shift in causative organisms has been documented, when comparing with historical reports. NTM are emerging organisms causing lymphadenopathy. Strict hygiene conditions are essential when performing a tattoo.
Topics: Humans; Nontuberculous Mycobacteria; Sepsis; Skin Diseases; Staphylococcal Infections; Staphylococcus aureus; Tattooing
PubMed: 33902933
DOI: 10.1016/j.medcli.2021.01.014 -
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 -
PLoS Neglected Tropical Diseases Mar 2021Leprosy is a chronic bacterial infection caused by Mycobacterium leprae, which may lead to physical disability, stigma, and discrimination. The chronicity of the disease... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Leprosy is a chronic bacterial infection caused by Mycobacterium leprae, which may lead to physical disability, stigma, and discrimination. The chronicity of the disease and disabilities are the prime contributors to the disease burden of leprosy. The current figures of the disease burden in the 2017 global burden of disease study, however, are considered to be under-estimated. In this study, we aimed to systematically review the literature and perform individual patient data meta-analysis to estimate new disability weights for leprosy, using Health-Related Quality of Life (HRQOL) data.
METHODOLOGY/PRINCIPAL FINDINGS
The search strategy included all major databases with no restriction on language, setting, study design, or year of publication. Studies on human populations that have been affected by leprosy and recorded the HRQOL with the Short form tool, were included. A consortium was formed with authors who could share the anonymous individual-level data of their study. Mean disability weight estimates, sorted by the grade of leprosy disability as defined by WHO, were estimated for individual participant data and pooled using multivariate random-effects meta-analysis. Eight out of 14 studies from the review were included in the meta-analysis due to the availability of individual-level data (667 individuals). The overall estimated disability weight for grade 2 disability was 0.26 (95%CI: 0.18-0.34). For grade 1 disability the estimated weight was 0.19 (95%CI: 0.13-0.26) and for grade 0 disability it was 0.13 (95%CI: 0.06-0.19). The revised disability weight for grade 2 leprosy disability is four times higher than the published GBD 2017 weights for leprosy and the grade 1 disability weight is nearly twenty times higher.
CONCLUSIONS/SIGNIFICANCE
The global burden of leprosy is grossly underestimated. Revision of the current disability weights and inclusion of disability caused in individuals with grade 0 leprosy disability will contribute towards a more precise estimation of the global burden of leprosy.
Topics: Disabled Persons; Global Burden of Disease; Humans; Leprosy; Quality of Life
PubMed: 33651814
DOI: 10.1371/journal.pntd.0009209