-
Microorganisms Jun 2024The Esx-1 family proteins of the Type VII secretion systems of and have been assessed and are frequently used as candidates for tuberculosis (TB) diagnosis in both...
The Presence of and and Other Gene Orthologs of the RD 1 Region in Non-Tuberculous Mycobacteria, Mycolicibacteria, Mycobacteroides and Mycolicibacter as Possible Impediments for the Diagnosis of (Animal) Tuberculosis.
The Esx-1 family proteins of the Type VII secretion systems of and have been assessed and are frequently used as candidates for tuberculosis (TB) diagnosis in both humans and animals. The presence of ESAT-6 and CFP 10 proteins, which are the most immunogenic proteins of the Esx-1 system and have been widely investigated for the immunodiagnosis of tuberculosis, in some and in , poses limitations for their use in specific diagnoses of TB. As such, to improve the specificity of the ESAT-6/CFP 10-based cell-mediated immunity (CMI) assays, other proteins encoded by genes within and outside the RD 1 region of the esx-1 locus have been evaluated as candidate antigens for CMI, as well as to investigate humoral responses in combination with ESAT-6 and or CFP 10, with varying specificity and sensitivity results. Hence, in this study, we evaluated various non-tuberculous mycobacteria (NTM), , and species genomes available on the NCBI database for the presence and composition of the RD1 region of the esx-1 locus. In addition, we also assayed by polymerase chain reaction (PCR) and sequencing of available in our culture collection for the presence and sequence diversity of and genes encoding ESAT-6 and CFP 10, respectively. Whole genome sequence (WGS) data analysis revealed the presence of RD 1 gene orthologs in 70 of the over 100 published genomes of pathogenic and non- pathogenic other than tuberculosis. Among species evaluated from our culture collection, in addition to earlier reports of the presence of and in certain , , and sp. N845T were also found to harbour orthologs of both genes. Orthologs of only were detected in , and , whereas in , and , only orthologs were detected. A phylogenetic analysis based on and sequences separated slow-growing from rapidly growing bacteria. These findings strengthen previous suggestions that and may be encoded in the majority of . The role of the Esx-1 system in both pathogenic and non-pathogenic needs further investigation, as these species may pose limitations to immunological assays for TB.
PubMed: 38930534
DOI: 10.3390/microorganisms12061151 -
Tropical Medicine and Infectious Disease Jun 2024The in vitro cultivation of has not been possible since it was described as causing leprosy, and the limitation of animal models for clinical aspects makes studies on...
The in vitro cultivation of has not been possible since it was described as causing leprosy, and the limitation of animal models for clinical aspects makes studies on leprosy and bacteria-human host interaction a challenge. Our aim was to standardize the ex vivo skin model (hOSEC) to maintenance and study of as an alternative animal model. Bacillary suspensions were inoculated into human skin explants and sustained in DMEM medium for 60 days. Explants were evaluated by RT-PCR-16SrRNA and cytokine gene expression. The viability and infectivity of bacilli recovered from explants (D28 and D60) were evaluated using the Shepard's model. All explants were RT-PCR-16SrRNA positive. The viability and infectivity of recovered bacilli from explants, analyzed after 5 months of inoculation in mice, showed an average positivity of 31%, with the highest positivity in the D28 groups (80%). Furthermore, our work showed different patterns in cytokine gene expression (TGF-β, IL-10, IL-8, and TNF-α) in the presence of alive or dead bacilli. Although changes can be made to improve future experiments, our results have demonstrated that it is possible to use the hOSEC to maintain for 60 days, interacting with the host system, an important step in the development of experimental models for studies on the biology of the bacillus, its interactions, and drug susceptibility.
PubMed: 38922047
DOI: 10.3390/tropicalmed9060135 -
Tropical Medicine and Infectious Disease Jun 2024The study aimed to characterize patients with leprosy admitted to Fontilles throughout the 20th and 21st centuries, focusing on differences across three periods (I, II,...
BACKGROUND
The study aimed to characterize patients with leprosy admitted to Fontilles throughout the 20th and 21st centuries, focusing on differences across three periods (I, II, and III). It also explored variables linked to patient survival.
METHODS
This was a retrospective descriptive study analyzing the medical records of Fontilles patients from 1909 to 2020. It assessed 26 clinical, sociodemographic, and temporal variables ( = 2652).
RESULTS
Most patients were male, single, multibacillary (MB), and farmers, from Andalusia and the Valencian Community. The origin of patients shifted over time towards being mostly foreign-born in period III. More than a half were previously admitted and had family members with leprosy. While leprosy reactions decreased over time, neurological symptoms were increasingly diagnosed. The age at onset, admission, and death increased progressively over time. The survival of patients with leprosy at Fontilles depended on the age at admission and the period.
CONCLUSIONS
Improved knowledge, services, and awareness regarding leprosy led to increased age at onset and more favorable outcomes. The prolonged time between symptom onset and diagnosis indicates that leprosy is still a neglected disease. Although MB forms are more severe, leprosy classification did not significantly impact the survival rates of patients at Fontilles.
PubMed: 38922042
DOI: 10.3390/tropicalmed9060130 -
International Journal of... Apr 2024Leprosy, caused by the bacterium Mycobacterium leprae, is known to primarily affect the skin and peripheral nerves. We present a rare case of leprosy initially...
Leprosy, caused by the bacterium Mycobacterium leprae, is known to primarily affect the skin and peripheral nerves. We present a rare case of leprosy initially manifesting as demyelinating polyneuropathy. A 46-year-old female presented with progressive weakness, tingling, and numbness in her extremities. Nerve conduction studies revealed evidence of demyelination, prompting further investigations. Skin slit-skin smears confirmed the diagnosis of leprosy, with the presence of acid-fast bacilli. The patient was subsequently started on multidrug therapy, leading to significant clinical improvement. This case highlights the importance of considering leprosy as a differential diagnosis in patients presenting with demyelinating polyneuropathy, especially in endemic regions.
Topics: Humans; Female; Middle Aged; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Leprosy; Diagnosis, Differential; Mycobacterium leprae; Skin; Leprostatic Agents
PubMed: 38916395
DOI: 10.4103/ijmy.ijmy_39_24 -
Indian Pediatrics Jun 2024To compare the diagnostic efficacy of Multiplex polymerase chain reaction (PCR), Mycobacterium leprae-specific repetitive element (RLEP) PCR and loop-mediated isothermal...
OBJECTIVE
To compare the diagnostic efficacy of Multiplex polymerase chain reaction (PCR), Mycobacterium leprae-specific repetitive element (RLEP) PCR and loop-mediated isothermal amplification (LAMP) PCR in the diagnosis of pediatric leprosy as an alternative to slit-skin smear (SSS) examination.
METHODS
A cross-sectional study was performed on 26 children aged 0-18 years with characteristic skin lesions of leprosy. SSS examination for acid fast bacilli (AFB) was performed for all children. Additionally, urine, stool and blood samples were tested by three PCR techniques - Multiplex, RLEP and LAMP. The results of these tests were compared with each other and with results of SSS examination for acid fast bacilli (AFB) using appropriate statistical tests.
RESULTS
Out of 26 patients studied, SSS examination was positive for AFB in 7 cases (26.9%). In blood samples, the positivity of Multiplex PCR, RLEP PCR and LAMP PCR was 84.6%, 80.8%, and 80.8%, respectively. Multiplex PCR in blood samples was positive in 100% (n = 7) of SSS positive cases and 84.2% (16 out of 19) of the SSS negative cases (P < 0.001). The positivity of all PCR methods in urine and stool samples was significantly lesser than in blood.
CONCLUSION
Multiplex PCR in blood sample is a superior diagnostic tool for pediatric leprosy compared to RLEP PCR and LAMP PCR, as well as SSS examination.
PubMed: 38910370
DOI: No ID Found -
Molecular Diversity Jun 2024Leprosy, caused by Mycobacterium leprae, remains a significant global health challenge, necessitating innovative approaches to therapeutic intervention. This study...
Leprosy, caused by Mycobacterium leprae, remains a significant global health challenge, necessitating innovative approaches to therapeutic intervention. This study employs advanced computational drug discovery techniques to identify potential inhibitors against the ML2640c protein, a key factor in the bacterium's ability to infect and persist within host cells. Utilizing a comprehensive methodology, including virtual screening, re-docking, molecular dynamics simulations, and free energy calculations, we screened a library of compounds for their interaction with ML2640c. Four compounds (24349836, 26616083, 26648979, and 26651264) demonstrated promising inhibitory potential, each exhibiting unique binding energies and interaction patterns that suggest a strong likelihood of disrupting the protein function. The study highlights the efficacy of computational methods in identifying potential therapeutic candidates, presenting compound 26616083 as a notably potent inhibitor due to its excellent binding affinity and stability. Our findings offer a foundation for future experimental validation and optimization, marking a significant step forward in the development of new treatments for leprosy. This research not only advances the fight against leprosy but also showcases the broader applicability of computational drug discovery in tackling infectious diseases.
PubMed: 38900332
DOI: 10.1007/s11030-024-10902-z -
Indian Journal of Dermatology,... Jun 2024Mycobacterium Indicus Pranii (MIP) vaccine is a killed vaccine developed in India for leprosy with immunotherapeutic as well as immunoprophylactic effects. MIP, earlier... (Review)
Review
Mycobacterium Indicus Pranii (MIP) vaccine is a killed vaccine developed in India for leprosy with immunotherapeutic as well as immunoprophylactic effects. MIP, earlier known as Mycobacterium welchii, is a rapidly growing non-pathogenic mycobacterium. The novelty of this bacterium is due to its translational application as an immunotherapeutic agent. When administered intradermally, the vaccine induces cell-mediated immunity in the host towards Mycobacterium leprae. It leads to faster clinical and histopathological improvement, rapid bacillary clearance, and also lepromin conversion in anergic leprosy patients. The beneficial role of the MIP vaccine in augmenting the therapeutic efficacy of Multidrug Therapy (MDT), particularly in highly bacillated leprosy patients, is well documented in various studies from India. The role of the vaccine in reactional states is controversial, with varied results in different studies. Overall, it is found to decrease the frequency of type 2 lepra reactions and is useful in recalcitrant erythema nodosum leprosum. Even though there may be an increased likelihood of type 1 reactions, no additional nerve function impairment is attributed to the vaccine in various studies. In household contacts of leprosy who are administered MIP, it is noted to confer protection from disease lasting up to 10 years. It may prove to be a cost-effective strategy in national leprosy programmes. Apart from local injection site reactions, the vaccine is relatively safe, but it is not recommended in pregnancy and lactation. This article provides an overview of the MIP vaccine's clinical application in the context of leprosy spanning over 40 years. It also considers the vaccine's possible future applications in the management of disease-related complications and achieving the long-term goal of zero leprosy.
PubMed: 38899419
DOI: 10.25259/IJDVL_1172_2023 -
BMC Infectious Diseases Jun 2024Leprosy, or Hansen's disease, is a chronic infectious disease caused by Mycobacterium leprae. Togo achieved the target of eliminating leprosy as a public health problem...
BACKGROUND
Leprosy, or Hansen's disease, is a chronic infectious disease caused by Mycobacterium leprae. Togo achieved the target of eliminating leprosy as a public health problem in 2000 (less than 1 case/10 000 population). However, new cases of leprosy are still being reported. The aim of this study was to describe and map trends of leprosy cases notified in Togo from 2010 to 2022.
METHODS
This was a descriptive cross-sectional study covering a thirteen-year period from January 1, 2010, to December 31, 2022. The data of the study were leprosy surveillance system's data collected monthly between 2010 and 2022. The estimated number of leprosy cases and the incidence rate of leprosy cases were reported for the whole population by region, by district, by calendar year (2010-2022) and by target sub-population (children under 15, women and people with disabilities). Observed case incidence rates were mapped by health district and by year.
RESULTS
From January 1, 2010, to December 31, 2022, 1031 new cases of leprosy were diagnosed in Togo. The median age of subjects was 46 years (interquartile range: 33-60), with extremes from 4 to 96 years. Half the subjects were women (50.7%). Variations in the leprosy incidence rate by year show an increase between 2010 and 2022, from 0.7 cases /100,000 population to 1.1 /100,000 population respectively. From 2010 to 2022, the proportion of cases in children remained low, between 0 and 9%. The proportion of women fluctuated between 39.7% and 67.2% between 2010 and 2017, then stabilized at an average of 50% between 2018 and 2022. The proportion of multi-bacillary leprosy cases increased quasi-linearly between 2010 and 2022, from 70 to 96.6%. Mapping of leprosy cases showed that leprosy was notified in all Togo health districts during the study period, apart from the Lacs district, which reported no leprosy cases.
CONCLUSION
Togo has achieved the elimination of leprosy as a public health problem. However, the increase in the number of new leprosy cases and the proportion of leprosy cases in children indicate that transmission of the disease is continuing and that supplementary measures are needed.
Topics: Humans; Togo; Leprosy; Cross-Sectional Studies; Female; Incidence; Male; Middle Aged; Adult; Adolescent; Child; Young Adult; Child, Preschool; Disease Eradication; Aged
PubMed: 38880867
DOI: 10.1186/s12879-024-09492-w -
Toxoplasma gondii infection and high levels of IgE are associated to erythema nodosum leprosy (ENL).PloS One 2024Leprosy is a chronic infectious disease caused by the bacillus Mycobacterium leprae. The disease may evolve for inflammatory reactions, reversal reaction (RR) and...
Leprosy is a chronic infectious disease caused by the bacillus Mycobacterium leprae. The disease may evolve for inflammatory reactions, reversal reaction (RR) and erythema nodosum leprosum (ENL), the major cause of irreversible neuropathy in leprosy, which occur in 1 in 3 people with leprosy, even with effective treatment of M. leprae. Leprosy remains persistently endemic in our region where it predominantly affects lowest socioeconomic conditions people, as Toxoplasma gondii infection in the municipality studied. Previously, we have shown T. gondii coinfection as a risk marker for leprosy, mainly in its severe form. This present study assessed whether T. gondii infection is also a risk factor for leprosy reactions and the predictive value of immunoglobulin production prior to development of leprosy reactions. Patients with leprosy (n = 180), co-infected or not with T. gondii, had their serum investigated for levels of IgA, IgE, IgG1, IgG2, IgG3 and IgG4 anti-PGL-1 by ELISA prior to development of leprosy reactions. The serologic prevalence for T. gondii infection was 87.7% in leprosy reaction patients reaching 90.9% in those with ENL. The leprosy reaction risk increased in T. gondii seropositive individuals was two-fold ([OR] = 2.366; 95% confidence interval [CI 95%]: 1.024-5.469) higher than those seronegative, and considering the risk of ENL, this increase was even more evident (OR = 6.753; 95% CI: 1.050-72.85) in coinfected individuals. When evaluated the prediction of anti-PGL-1 immunoglobulin levels for development of leprosy reactions in patients coinfected or not with T. gondii, only the increase IgE levels were associated to occurrence of reactional episodes of leprosy, specifically ENL type, in patients coinfected with T. gondii, compared to those not coinfected or no reaction. Thus, the immunomodulation in co-parasitism T. gondii-M. leprae suggest increased levels of IgE as a biomarker for early detection of these acute inflammatory episodes and thereby help prevent permanent neuropathy and disability in leprosy patients.
Topics: Humans; Toxoplasmosis; Erythema Nodosum; Female; Male; Adult; Immunoglobulin E; Middle Aged; Toxoplasma; Coinfection; Mycobacterium leprae; Young Adult; Adolescent; Risk Factors; Aged; Leprosy, Lepromatous
PubMed: 38865430
DOI: 10.1371/journal.pone.0300704 -
Cureus May 2024Leprosy, caused by the complex, manifests as a chronic infection. Its hallmark presentation involves the neurocutaneous syndrome, characterized by peripheral nerve...
Leprosy, caused by the complex, manifests as a chronic infection. Its hallmark presentation involves the neurocutaneous syndrome, characterized by peripheral nerve involvement and dermatologic lesions. Neurological complications significantly contribute to disability in leprosy patients. Peripheral neuropathy may manifest acutely or chronically, in either axonal or demyelinating forms, and can present as mononeuropathy, mononeuropathy multiplex, or polyneuropathy. The diverse clinical presentations emphasize the importance of considering leprosy in the differential diagnosis of peripheral neuropathy, enabling appropriate investigative approaches. Skin and nerve biopsies, slit skin smears, and nerve conduction studies serve as crucial diagnostic tools for identifying peripheral nerve involvement in leprosy. In this paper, we present three cases of leprosy with peripheral nerve involvement, discussing their clinical spectrum, diagnostic approach, and management.
PubMed: 38854261
DOI: 10.7759/cureus.59884