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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 -
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 -
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 -
PLoS Neglected Tropical Diseases Apr 2020Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae) and the more recently discovered Mycobacterium lepromatosis (M. lepromatosis). The two...
Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae) and the more recently discovered Mycobacterium lepromatosis (M. lepromatosis). The two leprosy bacilli cause similar pathologic conditions. They primarily target the skin and the peripheral nervous system. Currently it is considered a Neglected Tropical Disease, being endemic in specific locations within countries of the Americas, Asia, and Africa, while in Europe it is only rarely reported. The reason for a spatial inequality in the prevalence of leprosy in so-called endemic pockets within a country is still largely unexplained. A systematic review was conducted targeting leprosy transmission research data, using PubMed and Scopus as sources. Publications between January 1, 1945 and July 1, 2019 were included. The transmission pathways of M. leprae are not fully understood. Solid evidence exists of an increased risk for individuals living in close contact with leprosy patients, most likely through infectious aerosols, created by coughing and sneezing, but possibly also through direct contact. However, this systematic review underscores that human-to-human transmission is not the only way leprosy can be acquired. The transmission of this disease is probably much more complicated than was thought before. In the Americas, the nine-banded armadillo (Dasypus novemcinctus) has been established as another natural host and reservoir of M. leprae. Anthroponotic and zoonotic transmission have both been proposed as modes of contracting the disease, based on data showing identical M. leprae strains shared between humans and armadillos. More recently, in red squirrels (Sciurus vulgaris) with leprosy-like lesions in the British Isles M. leprae and M. lepromatosis DNA was detected. This finding was unexpected, because leprosy is considered a disease of humans (with the exception of the armadillo), and because it was thought that leprosy (and M. leprae) had disappeared from the United Kingdom. Furthermore, animals can be affected by other leprosy-like diseases, caused by pathogens phylogenetically closely related to M. leprae. These mycobacteria have been proposed to be grouped as a M. leprae-complex. We argue that insights from the transmission and reservoirs of members of the M. leprae-complex might be relevant for leprosy research. A better understanding of possible animal or environmental reservoirs is needed, because transmission from such reservoirs may partly explain the steady global incidence of leprosy despite effective and widespread multidrug therapy. A reduction in transmission cannot be expected to be accomplished by actions or interventions from the human healthcare domain alone, as the mechanisms involved are complex. Therefore, to increase our understanding of the intricate picture of leprosy transmission, we propose a One Health transdisciplinary research approach.
Topics: Animals; Armadillos; Disease Reservoirs; Disease Transmission, Infectious; Global Health; Humans; Incidence; Leprosy; Mycobacterium; Mycobacterium leprae; Prevalence; Sciuridae
PubMed: 32339201
DOI: 10.1371/journal.pntd.0008276 -
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 -
PLoS Neglected Tropical Diseases Mar 2020Understanding the prevalence of M. leprae infection in armadillos is important because of evidence from Brazil and other countries of an association between contact with... (Meta-Analysis)
Meta-Analysis
Understanding the prevalence of M. leprae infection in armadillos is important because of evidence from Brazil and other countries of an association between contact with armadillos and the development of Hansen's Disease (leprosy). Our aim was to characterize studies which have investigated natural M. leprae infection in wild armadillos in Brazil, and to quantify and explore variability in the reported prevalence of infection. We conducted a systematic review (PROSPERO CRD42019155277) of publications in MEDLINE, EMBASE, Global Health, Scopus, LILACS, Biblioteca Digital Brasileira de Teses e Dissertações, Catálogo de Teses e Dissertações de CAPES, and Biblioteca Virtual em Saúde up to 10/2019 using Mesh and text search terms (in English, Portuguese, Spanish, and French). The 10 included studies represented a total sample of 302 armadillos comprising 207 (69%) Dasypus novemcinctus, 67 (22%) Euphractus sexcinctus, 16 (5%) Priodontes maximus, 10 (3%) Cabassous unicinctus, and 2 (1%) Cabassous tatouay from 7 different states. Methods used included histopathology (4 studies), PGL-1 and LID-1 antigen detection (4 studies) and examination for clinical signs of disease (4 studies). Eight studies used PCR of which 7 targeted the RLEP repetitive element and 3 tested for inhibitory substances. M. leprae prevalence by PCR ranged from 0% (in 3 studies) to 100% in one study, with a summary estimate of 9.4% (95% CI 0.4% to 73.1%) and a predictive interval of 0-100%. The average prevalence is equivalent to 1 in 10 armadillos in Brazil being infected with M. leprae, but wide variation in sample estimates means that the prevalence in any similar study would be entirely unpredictable. We propose instead that future studies aim to investigate transmission and persistence of M. leprae within and between armadillo populations, meanwhile adopting the precautionary principle to protect human health and an endangered species in Brazil.
Topics: Animals; Animals, Wild; Armadillos; Brazil; DNA, Bacterial; Databases, Factual; Geographic Mapping; Leprosy; Mycobacterium leprae; Polymerase Chain Reaction; Prevalence; Repetitive Sequences, Nucleic Acid; Zoonoses
PubMed: 32203502
DOI: 10.1371/journal.pntd.0008127 -
BMC Infectious Diseases Jan 2020To evaluate the effectiveness and safety of the World Health Organization antibiotic regimen for the treatment of paucibacillary (PB) and multibacillary (MB) leprosy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To evaluate the effectiveness and safety of the World Health Organization antibiotic regimen for the treatment of paucibacillary (PB) and multibacillary (MB) leprosy compared to other available regimens.
METHODS
We performed a search from 1982 to July 2018 without language restriction. We included randomized controlled trials, quasi-randomized trials, and comparative observational studies (cohorts and case-control studies) that enrolled patients of any age with PB or MB leprosy that were treated with any of the leprosy antibiotic regimens established by the WHO in 1982 and used any other antimicrobial regimen as a controller. Primary efficacy outcomes included: complete clinical cure, clinical improvement of the lesions, relapse rate, treatment failure. Data were pooled using a random effects model to estimate the treatment effects reported as relative risk (RR) with 95% confidence intervals (CI).
RESULTS
We found 25 eligible studies, 11 evaluated patients with paucibacillary leprosy, while 13 evaluated patients with MB leprosy and 1 evaluated patients of both groups. Diverse regimen treatments and outcomes were studied. Complete cure at 6 months of multidrug therapy (MDT) in comparison to rifampin-ofloxacin-minocycline (ROM) found RR of 1.06 (95% CI 0.88-1.27) in five studies. Whereas six studies compare the same outcome at different follow up periods between 6 months and 5 years, according to the analysis ROM was not better than MDT (RR of 1.01 (95% CI 0.78-1.31)) in PB leprosy.
CONCLUSION
Not better treatment than the implemented by the WHO was found. Diverse outcome and treatment regimens were studied, more statements to standardized the measurements of outcomes are needed.
Topics: Adolescent; Adult; Aged; Child; Clinical Protocols; Drug Therapy, Combination; Female; Humans; Leprostatic Agents; Leprosy, Multibacillary; Leprosy, Paucibacillary; Male; Middle Aged; Minocycline; Mycobacterium leprae; Neglected Diseases; Ofloxacin; Recurrence; Rifampin; Treatment Failure; World Health Organization; Young Adult
PubMed: 31959113
DOI: 10.1186/s12879-019-4665-0