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Seminars in Immunology Oct 2018Leprosy is still a considerable health threat in pockets of several low and middle income countries worldwide where intense transmission is witnessed, and often results... (Review)
Review
Leprosy is still a considerable health threat in pockets of several low and middle income countries worldwide where intense transmission is witnessed, and often results in irreversible disabilities and deformities due to delayed- or misdiagnosis. Early detection of leprosy represents a substantial hurdle in present-day leprosy health care. The dearth of timely diagnosis has, however, particularly severe consequences in the case of inflammatory episodes, designated leprosy reactions, which represent the major cause of leprosy-associated irreversible neuropathy. There is currently no accurate, routine diagnostic test to reliably detect leprosy reactions, or to predict which patients will develop these immunological exacerbations. Identification of host biomarkers for leprosy reactions, particularly if correlating with early onset prior to development of clinical symptoms, will allow timely interventions that contribute to decreased morbidity. Development of a point-of-care (POC) test based on such correlates would be a definite game changer in leprosy health care. In this review, proteomic-, transcriptomic and metabolomic research strategies aiming at identification of host biomarker-based correlates of leprosy reactions are discussed, next to external factors associated with occurrence of these episodes. The vast diversity in research strategies combined with the variability in patient- and control cohorts argues for harmonisation of biomarker discovery studies with geographically overarching study sites. This will improve identification of specific correlates associated with risk of these damaging inflammatory episodes in leprosy and subsequent application to rapid field tests.
Topics: Antibodies, Bacterial; Biomarkers; CD30 Ligand; Cation Transport Proteins; Delayed Diagnosis; Disease Progression; Endpoint Determination; Humans; Leprosy; Metabolome; Mycobacterium leprae; Point-of-Care Testing; Systems Biology; Toll-Like Receptors; Transcriptome
PubMed: 29950273
DOI: 10.1016/j.smim.2018.06.003 -
Bulletin of the World Health... Apr 2024The World Health Organization (WHO) aims to reduce new leprosy cases by 70% by 2030, necessitating advancements in leprosy diagnostics. Here we discuss the development...
The World Health Organization (WHO) aims to reduce new leprosy cases by 70% by 2030, necessitating advancements in leprosy diagnostics. Here we discuss the development of two WHO's target product profiles for such diagnostics. These profiles define criteria for product use, design, performance, configuration and distribution, with a focus on accessibility and affordability. The first target product profile outlines requirements for tests to confirm diagnosis of leprosy in individuals with clinical signs and symptoms, to guide multidrug treatment initiation. The second target product profile outlines requirements for tests to detect or infection among asymptomatic contacts of leprosy patients, aiding prophylactic interventions and prevention. Statistical modelling was used to assess sensitivity and specificity requirements for these diagnostic tests. The paper highlights challenges in achieving high specificity, given the varying endemicity of and identifying target analytes with robust performance across leprosy phenotypes. We conclude that diagnostics with appropriate product design and performance characteristics are crucial for early detection and preventive intervention, advocating for the transition from leprosy management to prevention.
Topics: Humans; Leprosy; Mycobacterium leprae; Sensitivity and Specificity; Models, Statistical; Early Diagnosis
PubMed: 38562197
DOI: 10.2471/BLT.23.290881 -
Frontiers in Cellular and Infection... 2018Triatominae bugs are the vectors of Chagas disease, a major concern to public health especially in Latin America, where vector-borne Chagas disease has undergone... (Review)
Review
Triatominae bugs are the vectors of Chagas disease, a major concern to public health especially in Latin America, where vector-borne Chagas disease has undergone resurgence due mainly to diminished triatomine control in many endemic municipalities. Although the majority of Triatominae species occurs in the Americas, species belonging to the genus occur in India, and species belonging to the complex have been also identified in Africa, the Middle East, South-East Asia, and in the Western Pacific. Not all of Triatominae species have been found to be infected with , but the possibility of establishing vector transmission to areas where Chagas disease was previously non-endemic has increased with global population mobility. Additionally, the worldwide distribution of triatomines is concerning, as they are able to enter in contact and harbor other pathogens, leading us to wonder if they would have competence and capacity to transmit them to humans during the bite or after successful blood feeding, spreading other infectious diseases. In this review, we searched the literature for infectious agents transmitted to humans by Triatominae. There are reports suggesting that triatomines may be competent vectors for pathogens such as , and , and that triatomine infection with other microrganisms may interfere with triatomine- interactions, altering their competence and possibly their capacity to transmit Chagas disease.
Topics: Animals; Bacteria; Bartonella; Chagas Disease; Communicable Diseases; Humans; Insect Vectors; Mycobacterium leprae; Serratia marcescens; Triatoma; Triatominae; Trypanosoma; Trypanosoma cruzi; Viruses
PubMed: 30505806
DOI: 10.3389/fcimb.2018.00405 -
Iranian Journal of Microbiology Apr 2023Leprosy remains an important health problem worldwide. It is one of the oldest recorded diseases of humankind. In this study, we expanded the analysis of the geographic...
BACKGROUND AND OBJECTIVES
Leprosy remains an important health problem worldwide. It is one of the oldest recorded diseases of humankind. In this study, we expanded the analysis of the geographic distribution of by investigating SNPs and genotypes in South Central Coast and Central Highlands clinical isolates, providing insights into the distribution and transmission of leprosy in Vietnam and in this geographic region.
MATERIALS AND METHODS
27 clinical isolates from the patients, determined the genotypes of by SNP and polymorphism. SNP genotyping was performed by PCR amplification and sequencing, genotyping by PCR amplification and electrophoresis.
RESULTS
All of 27 DNA samples (100%) were positive with RLEP TaqMan PCR (Ct value range is 18-32 on 3 replicates). SNP type 1 was identified in 15 isolates (56%), while SNP type 3 was detected in 12 samples (44%). SNP type 2 and type 4, were not detected. The 6-base repeat region of the gene was amplified by PCR and analyzed by 4% MetaPhor™ agarose gel electrophoresis. All isolates yielded amplification products of 91-bp, but not 97-bp.
CONCLUSION
This study showed that 56% of isolates belonged to type 1, 44% to type 3. In addition, all samples have the 3-copy hexamer genotype in the gene.
PubMed: 37193237
DOI: 10.18502/ijm.v15i2.12470 -
WMJ : Official Publication of the State... Jul 2023Leprosy is a life-threatening infection caused by with an average 5-year long incubation period. It is curable when treated early. Early diagnosis requires knowledge of...
INTRODUCTION
Leprosy is a life-threatening infection caused by with an average 5-year long incubation period. It is curable when treated early. Early diagnosis requires knowledge of its myriad clinical features as risk factors may not be readily apparent.
CASE PRESENTATION
We report the case of a male patient from Wisconsin who tested positive for leprosy without a known exposure or recent travel to endemic areas.
DISCUSSION
The clinical presentation of leprosy exists on a spectrum and correlates with cell immunity levels. The Ridley-Jopling and World Health Organization classifications are used to define leprosy subtypes and guide treatment. Histopathologic examination may aid in diagnosis of suspicious presentations.
CONCLUSIONS
Leprosy may present with nonspecific clinical features and elevated inflammatory markers leading to a misdiagnosis. It should be considered on the differential diagnosis for suspicious presentations and appropriately worked up with various diagnostic modalities. A multidisciplinary approach to treatment may prevent spread and permanent damage.
Topics: Male; Humans; Leprosy; Mycobacterium leprae; Wisconsin
PubMed: 37494653
DOI: No ID Found -
Journal of Global Antimicrobial... Dec 2022As the only bactericidal drug in multidrug therapy is rifampicin, monitoring of antimicrobial resistance is important in leprosy patients. Therefore, we conducted a... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
As the only bactericidal drug in multidrug therapy is rifampicin, monitoring of antimicrobial resistance is important in leprosy patients. Therefore, we conducted a meta-analysis on the resistance of Mycobacterium leprae (M. leprae) to rifampicin and estimated drug resistance in different therapeutic states and regions.
METHODS
Embase, Medline, PubMed, and Web of Science were searched to identify studies between 1 January 1993 and 1 January 2022. Two independent reviewers extracted study data. Pooled cumulative incidences were computed using random-effects meta-analyses.
RESULTS
We included 32 papers describing the resistance of M. leprae to rifampicin (pooled cumulative incidences, 11% [95% confidence interval {CI}, 7% to 15%]). Therapeutic states and regional distribution were obtained for subgroup analyses. A total of 51 of 1135 new cases (pooled incidence, 10% [95% CI, 5% to 16%]) and 81 of 733 relapsed cases (pooled incidence, 20% [95% CI, 13% to 27%]) had rifampicin resistance. A total of 139 participants, including 11 patients with rifampicin resistance (pooled incidence, 42% [95% CI, -21% to 105%]), were nonresponsive and intractable cases. The incidence of rifampicin resistance was highest in the Western Pacific (pooled incidence, 21% [95% CI, 13% to 29%]) and lowest in the Americas (pooled incidence, 4% [95% CI, 1% to 7%]).
CONCLUSIONS
Drug resistance testing and a robust and rigorous surveillance system are recommended to detect the prevalence of drug resistance in leprosy.
Topics: Humans; Rifampin; Mycobacterium leprae; Prevalence; Drug Therapy, Combination; Leprostatic Agents; Drug Resistance, Bacterial; Leprosy
PubMed: 36055549
DOI: 10.1016/j.jgar.2022.08.021 -
Biochemistry. Biokhimiia Mar 2022Paleogenomics is one of the urgent and promising areas of interdisciplinary research in the today's world science. New genomic methods of ancient DNA (aDNA) analysis,... (Review)
Review
Paleogenomics is one of the urgent and promising areas of interdisciplinary research in the today's world science. New genomic methods of ancient DNA (aDNA) analysis, such as next generation sequencing (NGS) technologies, make it possible not only to obtain detailed genetic information about historical and prehistoric human populations, but also to study individual microbial and viral pathogens and microbiomes from different ancient and historical objects. Studies of aDNA of pathogens by reconstructing their genomes have so far yielded complete sequences of the ancient pathogens that played significant role in the history of the world: Yersinia pestis (plague), Variola virus (smallpox), Vibrio cholerae (cholera), HBV (hepatitis B virus), as well as the equally important endemic human infectious agents: Mycobacterium tuberculosis (tuberculosis), Mycobacterium leprae (leprosy), and Treponema pallidum (syphilis). Genomic data from these pathogens complemented the information previously obtained by paleopathologists and allowed not only to identify pathogens from the past pandemics, but also to recognize the pathogen lineages that are now extinct, to refine chronology of the pathogen appearance in human populations, and to reconstruct evolutionary history of the pathogens that are still relevant to public health today. In this review, we describe state-of-the-art genomic research of the origins and evolution of many ancient pathogens and viruses and examine mechanisms of the emergence and spread of the ancient infections in the mankind history.
Topics: DNA, Ancient; Genomics; History, Ancient; Humans; Mycobacterium leprae; Paleontology; Yersinia pestis
PubMed: 35526849
DOI: 10.1134/S0006297922030051 -
Memorias Do Instituto Oswaldo Cruz 2022Leprosy is curable by multidrug therapy (MDT) treatment regimen ranging from six to 12 months. The variable levels of tolerance and adherence among patients can,...
BACKGROUND
Leprosy is curable by multidrug therapy (MDT) treatment regimen ranging from six to 12 months. The variable levels of tolerance and adherence among patients can, however, result in treatment failure and the emergence of drug-resistant strains.
OBJECTIVES
Describe the impact of MDT over Mycobacterium leprae viability in patient's oral and nasal mucosa along treatment.
METHODS
Mycobacterium leprae viability was monitored by quantitative polymerase chain reaction (qPCR) quantification of 16S rRNA in lateral and contralateral scrapings of oral and nasal mucosa of 10 multibacillary patients along the initial five months of treatment.
FINDINGS
The results demonstrated high heterogenicity of M. leprae viability among patients and between nasal and oral samples. Of six patients who presented good adherence and tolerance to the treatment, only four displayed absence of M. leprae viability in both samples three months after the first MDT dose, while for the other two, the absence of M. leprae viability in the oral and nasal cavities was only detected five months after the first dose.
MAIN CONCLUSIONS
We concluded that qPCR of 16S rRNA for the determination of M. leprae viability in nasal and oral scraping samples could represent an interesting approach to monitor treatment efficacy.
Topics: Humans; Mycobacterium leprae; RNA, Ribosomal, 16S; Leprostatic Agents; Drug Therapy, Combination; Nasal Mucosa; DNA, Bacterial
PubMed: 36259791
DOI: 10.1590/0074-02760220058 -
Indian Journal of Dermatology,... 2018
Topics: Drug Resistance, Microbial; Humans; India; Leprostatic Agents; Leprosy; Mycobacterium leprae
PubMed: 29893300
DOI: 10.4103/ijdvl.IJDVL_343_18 -
BMC Microbiology Sep 2023Mycobacterium leprae (ML) is the pathogen that causes leprosy, which has a long history and still exists today. ML is an intracellular mycobacterium that dominantly...
BACKGROUND
Mycobacterium leprae (ML) is the pathogen that causes leprosy, which has a long history and still exists today. ML is an intracellular mycobacterium that dominantly induces leprosy by causing permanent damage to the skin, nerves, limbs and eyes as well as deformities and disabilities. Moreover, ML grows slowly and is nonculturable in vitro. Given the prevalence of leprosy, a highly sensitive and rapid method for the early diagnosis of leprosy is urgently needed.
RESULTS
In this study, we devised a novel tool for the diagnosis of leprosy by combining restriction endonuclease, real-time fluorescence analysis and multiple cross displacement amplification (E-RT-MCDA). To establish the system, primers for the target gene RLEP were designed, and the optimal conditions for E-RT-MCDA at 67 °C for 36 min were determined. Genomic DNA from ML, various pathogens and clinical samples was used to evaluate and optimize the E-RT-MCDA assay. The limit of detection (LoD) was 48.6 fg per vessel for pure ML genomic DNA, and the specificity of detection was as high as 100%. In addition, the detection process could be completed in 36 min by using a real-time monitor.
CONCLUSION
The E-RT-MCDA method devised in the current study is a reliable, sensitive and rapid technique for leprosy diagnosis and could be used as a potential tool in clinical settings.
Topics: Humans; Mycobacterium leprae; Sensitivity and Specificity; Leprosy; Skin; DNA; DNA, Bacterial; Nucleic Acid Amplification Techniques
PubMed: 37770823
DOI: 10.1186/s12866-023-03004-7