Non-Tuberculous Mycobacterial isolates from Panama: A retrospective 5-year analysis (2017-2021).

BACKGROUND: The genus Mycobacterium includes well-known bacteria such as M. tuberculosis causing tuberculosis and M. leprae causing leprosy. Additionally, various species collectively termed non-tuberculous mycobacteria (NTM) can cause infections in humans and animals, affecting individuals across all age groups and health conditions. However, information on NTM infection prevalence in Panama is limited. METHODS: This study conducted a retrospective analysis of clinical records from 2017 to 2021, specifically focusing on patients with NTM isolates. Data were categorized by variables like sex, age, HIV status, and sample source. RESULTS: Among the 4430 clinical records analyzed, 698 were linked to patients with NTM isolates. Of these patients, 397 were male, and 301 were female. Most female patients with NTM isolates (n = 190) were aged >45 to 85 years, while most male patients (n = 334) fell in the >25 to 75 years age group. A noteworthy proportion of male patients (n = 65) were aged 25-35 years. A significant age difference between male (median [min-max] = 53 years [3-90]) and female (median [61 years [6-94]) patients was observed (p < 0.001). Regarding HIV status, 77 positive individuals were male, and 19 were female (p < 0.001). Most samples (n = 566) were sputum samples, with additional pulmonary-associated samples such as broncho-alveolar lavage, tracheal secretions, and pleural fluid samples. Among extrapulmonary isolates (n = 48), sources included catheter secretions, intracellular fluids, peritoneal fluid, blood cultures, cerebrospinal fluid, bone marrow samples, and capillary transplant lesions. Specifically, the analysis identified the pathogenic microorganisms responsible for mycobacteriosis in Panama during the specific period 2017-2021, as M. fortuitum (34.4%), M. intracellulare (20.06%), and M. abscessus (13.75%), respectively. CONCLUSIONS: This study highlights the growing public health concern of NTM infections in Panama. The research provides valuable insights into the prevalence and distribution of NTM species in the country, offering a foundation for the development and implementation of effective prevention and control strategies for NTM infections in Panama.

Dermoscopic features of nails in Leprosy patients in a tertiary referral hospital in West Java, Indonesia.

INTRODUCTION: Leprosy is a chronic granulomatous infectious disease, mainly affecting the skin and peripheral nerves, caused by the obligate intracellular bacteria Mycobacterium leprae. The disease has been discussed in several review articles in recent research, but as far as we know, only a few have addressed the effects of leprosy on nails, especially those who examine the dermoscopic features of nails in leprosy patients. PURPOSES: We aimed to document nail changes in leprosy patients and identify any particular findings through dermoscopic examination. METHOD: This was an observational study conducted in the Dermatology and Venereology Clinic of Hasan Sadikin Hospital, West Java, Indonesia, from March 2023 through May 2023. All patients have established cases of leprosy, and the diagnosis is based on clinical and bacteriological examinations. Recruitment was done through total sampling. Dermoscopic examination of all fingernails and toenails was performed at 10x magnification using a handheld dermatoscope (Heine DELTA 20 T Dermatoscope) in polarized mode without the linkage fluid to document the dermoscopic features. RESULT: Of a total of 19 patients, 15 had nail changes due to leprosy. Out of 15 patients, 13 patients were male. Patients below 25 years old had more nail changes. Most of the patients had a duration of disease greater than two years. Both fingers and toes were involved in nine patients. In this study, the most common dermoscopic feature found was the longitudinal ridge. Other dermoscopic features found in this study were transverse lines, onycholysis, longitudinal melanonychia, leukonychia, subungual hemorrhage, subungual hyperkeratosis, anonychia, and onychorrexis. CONCLUSION: Nail changes are found in leprosy patients and have a wide variety of clinical appearances. A dermoscopy should be performed to assess nail changes in leprosy.

Epidemiology and treatment outcomes of recurrent tuberculosis in Tanzania from 2018 to 2021 using the National TB dataset.

BACKGROUND: Patients with recurrent TB have an increased risk of higher mortality, lower success rate, and a relatively feeble likelihood of treatment completion than those with new-onset TB. This study aimed to assess the epidemiology of recurrent TB in Tanzania; specifically, we aim to determine the prevalence of TB recurrence and factors associated with unfavourable treatment outcomes among patients with recurrent TB in Tanzania from 2018 to 2021. METHODS: In this cross-sectional study, we utilized Tanzania's routinely collected national TB program data. The study involved a cohort of TB patients over a fixed treatment period registered in the TB and Leprosy case-based District Health Information System (DHIS2-ETL) database from 2018 to 2021 in Tanzania. We included patients' sociodemographic and clinical factors, facility characteristics, and TB treatment outcomes. We conducted bivariate analysis and multivariable multi-level mixed effects logistic regression of factors associated with TB recurrence and TB treatment outcomes to account for the correlations at the facility level. A purposeful selection method was used; the multivariable model included apriori selected variables (Age, Sex, and HIV status) and variables with a p-value <0.2 on bivariate analysis. The adjusted odds ratio and 95% confidence interval were recorded, and a p-value of less than 0.05 was considered statistically significant. FINDINGS: A total of 319,717 participants were included in the study; the majority were adults aged 25-49 (44.2%, n = 141,193) and above 50 years (31.6%, n = 101,039). About two-thirds were male (60.4%, n = 192,986), and more than one-fifth of participants (22.8%, n = 72,396) were HIV positive. Nearly two in every hundred TB patients had a recurrent TB episode (2.0%, n = 6,723). About 10% of patients with recurrent TB had unfavourable treatment outcomes (9.6%, n = 519). The odds of poor treatment outcomes were two-fold higher for participants receiving treatment at the central (aOR = 2.24; 95% CI 1.33-3.78) and coastal zones (aOR = 2.20; 95% CI 1.40-3.47) than the northern zone. HIV-positive participants had 62% extra odds of unfavourable treatment outcomes compared to their HIV-negative counterparts (aOR = 1.62; 95% CI 1.25-2.11). Bacteriological TB diagnosis (aOR = 1.39; 95% CI 1.02-1.90) was associated with a 39% additional risk of unfavourable treatment outcomes as compared to clinical TB diagnosis. Compared to community-based DOT, patients who received DOT at the facility had 1.39 times the odds of poor treatment outcomes (aOR = 1.39; 95%CI 1.04-1.85). CONCLUSION: TB recurrence in Tanzania accounts for 2% of all TB cases, and it is associated with poor treatment outcomes. Unfavourable treatment outcomes were recorded in 10% of patients with recurrent TB. Poor TB treatment outcome was associated with HIV-positive status, facility-based DOT, bacteriologically confirmed TB and receiving treatment at the hospital level, differing among regions. We recommend post-treatment follow-up for patients with recurrent TB, especially those coinfected with HIV. We also propose close follow-up for patients treated at the hospital facility level and strengthening primary health facilities in TB detection and management to facilitate early treatment initiation.

Bioarchaeological investigation of individuals with suspected multibacillary leprosy from the mediaeval leprosarium of St Mary Magdalen, Winchester, Hampshire, UK.

Introduction. We have examined four burials from the St Mary Magdalen mediaeval leprosarium cemetery in Winchester, Hampshire, UK. One (Sk.8) was a male child, two (Sk.45 and Sk.52) were adolescent females and the fourth (Sk.512) was an adult male. The cemetery was in use between the 10th and 12th centuries. All showed skeletal lesions of leprosy. Additionally, one of the two females (Sk.45) had lesions suggestive of multi-cystic tuberculosis and the second (Sk.52) of leprogenic odontodysplasia (LO), a rare malformation of the roots of the permanent maxillary incisors.Gap statement. Relatively little is known of the manifestations of lepromatous leprosy (LL) in younger individuals from the archaeological record.Aims and Methodology. To address this, we have used ancient DNA testing and osteological examination of the individuals, supplemented with X-ray and microcomputed tomography (micro-CT) scan as necessary to assess the disease status.Results and Conclusions. The presence of Mycobacterium leprae DNA was confirmed in both females, and genotyping showed SNP type 3I-1 strains but with a clear genotypic variation. We could not confirm Mycobacterium tuberculosis complex DNA in the female individual SK.45. High levels of M. leprae DNA were found within the pulp cavities of four maxillary teeth from the male child (Sk.8) with LO, consistent with the theory that the replication of M. leprae in alveolar bone may interfere with root formation at key stages of development. We report our biomolecular findings in these individuals and review the evidence this site has contributed to our knowledge of mediaeval leprosy.

Development of a multivariate predictive model for dapsone adverse drug events in people with leprosy under standard WHO multidrug therapy.

BACKGROUND: The occurrence of adverse drug events (ADEs) during dapsone (DDS) treatment in patients with leprosy can constitute a significant barrier to the successful completion of the standardized therapeutic regimen for this disease. Well-known DDS-ADEs are hemolytic anemia, methemoglobinemia, hepatotoxicity, agranulocytosis, and hypersensitivity reactions. Identifying risk factors for ADEs before starting World Health Organization recommended standard multidrug therapy (WHO/MDT) can guide therapeutic planning for the patient. The objective of this study was to develop a predictive model for DDS-ADEs in patients with leprosy receiving standard WHO/MDT. METHODOLOGY: This is a case-control study that involved the review of medical records of adult (≥18 years) patients registered at a Leprosy Reference Center in Rio de Janeiro, Brazil. The cohort included individuals that received standard WHO/MDT between January 2000 to December 2021. A prediction nomogram was developed by means of multivariable logistic regression (LR) using variables. The Hosmer-Lemeshow test was used to determine the model fit. Odds ratios (ORs) and their respective 95% confidence intervals (CIs) were estimated. The predictive ability of the LRM was assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 329 medical records were assessed, comprising 120 cases and 209 controls. Based on the final LRM analysis, female sex (OR = 3.61; 95% CI: 2.03-6.59), multibacillary classification (OR = 2.5; 95% CI: 1.39-4.66), and higher education level (completed primary education) (OR = 1.97; 95% CI: 1.14-3.47) were considered factors to predict ADEs that caused standard WHO/MDT discontinuation. The prediction model developed had an AUC of 0.7208, that is 72% capable of predicting DDS-ADEs. CONCLUSION: We propose a clinical model that could become a helpful tool for physicians in predicting ADEs in DDS-treated leprosy patients.

Prevalence Trend and Clinical Profile of Leprosy Among the Indigenous Penan Community in Rural Baram, Sarawak, Malaysia: A Retrospective Study.

In Malaysia, despite achieving leprosy-elimination status in 1994, leprosy remains a public health issue among the indigenous Penan community in Sarawak. This study aimed to determine the prevalence trend and clinical profile of leprosy among the Penans in rural Baram, Sarawak, Malaysia. A retrospective records review was conducted on 10-year (2008-2018) time trend of annual prevalence rate and 5-year (2013-2018) Penan leprosy patient clinical profile. Out of the 257 new cases of leprosy reported in Sarawak, 42.8% were Penans, and 72.7% were from Baram. The annual Penan ethnic-specific prevalence rate ranged from 2.08 to 35.5/10 000. Forty-six cases were analyzed for clinical profile: There were more males, active case detection, and multibacillary leprosy. The prevalence trend of leprosy among the Penans in rural Baram exceeded recommended elimination targets. Majority of the cases were detected through active case detection, but cases were detected late. Interventions are needed to improve early diagnosis and detection to achieve elimination of leprosy.

Reverse Koebner phenomenon in erythema nodosum leprosum.

BACKGROUND: Erythema nodosum leprosum (ENL) is an immunologically mediated phenomenon complicating the course of leprosy. Reverse Koebner phenomenon is the term used to describe the sparing of previously injured or diseased skin by new skin lesions of the disease. METHODS: A middle-aged woman with a known case of lepromatous leprosy for the past year presented with an eruption of reddish painful nodules over her body. The lesions were found to characteristically spare the sites of previous scars. RESULTS: This sparing phenomenon of previous scar sites has been termed reverse Koebner phenomenon, a site of the body that offers greater resistance than the rest of the body to the onset of the disease, seen in various diseases, but it has never been described in ENL. CONCLUSION: This sparing of scar sites in ENL can be attributed to reverse Koebner phenomenon.

Evaluating active leprosy case identification methods in six districts of Nepal.

BACKGROUND: Nepal has achieved and sustained the elimination of leprosy as a public health problem since 2009, but 17 districts and 3 provinces with 41% (10,907,128) of Nepal's population have yet to eliminate the disease. Pediatric cases and grade-2 disabilities (G2D) indicate recent transmission and late diagnosis, respectively, which necessitate active and early case detection. This operational research was performed to identify approaches best suited for early case detection, determine community-based leprosy epidemiology, and identify hidden leprosy cases early and respond with prompt treatment. METHODS: Active case detection was undertaken in two Nepali provinces with the greatest burden of leprosy, Madhesh Province (40% national cases) and Lumbini Province (18%) and at-risk prison populations in Madhesh, Lumbini and Bagmati provinces. Case detection was performed by (1) house-to-house visits among vulnerable populations (n = 26,469); (2) contact examination and tracing (n = 7608); in Madhesh and Lumbini Provinces and, (3) screening prison populations (n = 4428) in Madhesh, Lumbini and Bagmati Provinces of Nepal. Per case direct medical and non-medical costs for each approach were calculated. RESULTS: New case detection rates were highest for contact tracing (250), followed by house-to-house visits (102) and prison screening (45) per 100,000 population screened. However, the cost per case identified was cheapest for house-to-house visits [Nepalese rupee (NPR) 76,500/case], followed by contact tracing (NPR 90,286/case) and prison screening (NPR 298,300/case). House-to-house and contact tracing case paucibacillary/multibacillary (PB:MB) ratios were 59:41 and 68:32; female/male ratios 63:37 and 57:43; pediatric cases 11% in both approaches; and grade-2 disabilities (G2D) 11% and 5%, respectively. Developing leprosy was not significantly different among household and neighbor contacts [odds ratios (OR) = 1.4, 95% confidence interval (CI): 0.24-5.85] and for contacts of MB versus PB cases (OR = 0.7, 95% CI 0.26-2.0). Attack rates were not significantly different among household contacts of MB cases (0.32%, 95% CI 0.07-0.94%) and PB cases (0.13%, 95% CI 0.03-0.73) (χ2 = 0.07, df = 1, P = 0.9) and neighbor contacts of MB cases (0.23%, 0.1-0.46) and PB cases (0.48%, 0.19-0.98) (χ2 = 0.8, df = 1, P = 0.7). BCG vaccination with scar presence had a significant protective effect against leprosy (OR = 0.42, 0.22-0.81). CONCLUSIONS: The most effective case identification approach here is contact tracing, followed by house-to-house visits in vulnerable populations and screening in prisons, although house-to-house visits are cheaper. The findings suggest that hidden cases, recent transmission, and late diagnosis in the community exist and highlight the importance of early case detection.

Mental health, stigma and the quality of life of people affected by neglected tropical diseases of the skin in Kasai Province, Democratic Republic of the Congo: a sex-disaggregated analysis.

BACKGROUND: Worldwide, persons affected by skin Neglected Tropical Diseases (NTDs) may experience stigma and discrimination, which could lead to impaired societal functioning and poor mental wellbeing. Evidence of comorbidity of NTDs and mental health conditions is dominated by Leprosy, largely lacking in post-conflict areas, and rarely disaggregated by sex. METHODS: This cross-sectional survey is the first to explore depression, anxiety, stigma, and quality of life amongst people affected by Lymphatic Filariasis, Buruli Ulcer, Onchocerciasis or Leprosy in the Democratic Republic of the Congo. After a census through active case identification, the survey was completed by 118 persons (response rate 94.4%). RESULTS: In total, 58.3% of men and 80.0% of women screened positive for major depressive disorder (PHQ-9). Symptoms indicative of generalised anxiety disorder (GAD-7) were displayed by 54.8% of men and 62.2% of women. Being female, having a disability, experiencing stigma and lower physical quality of life were predictors of depression. Anxiety was predicted by age, physical quality of life, disability (for men only) and environmental quality of life (for women only). CONCLUSIONS: Integrated, intersectoral and gender-sensitive initiatives are needed to respond to the many biopsychosocial challenges that persons affected face. CONTEXTE: Dans le monde entier, les personnes atteintes de maladies tropicales négligées (MTN) peuvent faire l'objet d'une stigmatisation et d'une discrimination, ce qui peut entraîner une altération du fonctionnement de la société et un mauvais bien-être mental. Les preuves de la comorbidité des MTN et des troubles de la santé mentale sont dominées par la lèpre, manquent largement dans les zones post-conflit et sont rarement ventilées par sexe. MÉTHODES UTILISÉES: Cette enquête transversale est la première à explorer la dépression, l'anxiété, la stigmatisation et la qualité de vie chez les personnes atteintes de filariose lymphatique, d'ulcère de Buruli, d'onchocercose ou de lèpre en République démocratique du Congo. Après un recensement par identification active des cas, 118 personnes ont répondu à l'enquête (taux de réponse 94,4%). RÉSULTATS: Au total, 58,3% des hommes et 80,0% des femmes ont été dépistés positifs pour un trouble dépressif majeur (PHQ-9). Des symptômes indiquant un trouble anxieux généralisé (GAD-7) ont été observés chez 54,8 % des hommes et 62,2 % des femmes. Le fait d'être une femme, d'avoir un handicap, d'être stigmatisé et d'avoir une qualité de vie physique inférieure était un facteur prédictif de la dépression. L'anxiété était prédite par l'âge, la qualité de vie physique, le handicap (pour les hommes uniquement) et la qualité de vie environnementale (pour les femmes uniquement). CONCLUSIONS: Des initiatives intégrées, intersectorielles et sensibles au genre sont nécessaires pour répondre aux nombreux défis biopsychosociaux auxquels sont confrontées les personnes touchées. ANTECEDENTES: En todo el mundo, las personas afectadas por Enfermedades Tropicales Desatendidas (ETD) cutáneas pueden sufrir estigmatización y discriminación, lo que podría conducir a un deterioro del funcionamiento social y a un bienestar mental deficiente. La evidencia científica sobre la comorbilidad de las ETD y las afecciones mentales está dominada por la lepra, en general insuficiente en zonas post-conflicto y rara vez se desglosan por sexo. MÉTODOS: Esta encuesta transversal es la primera que explora la depresión, la ansiedad, el estigma y la calidad de vida entre las personas afectadas por la filariasis linfática, la úlcera de Buruli, la oncocercosis o la lepra en la República Democrática del Congo. Tras un censo mediante identificación activa de casos, la encuesta fue completada por 118 personas (tasa de respuesta del 94,4%). RESULTADOS: En total, el 58,3% de los hombres y el 80,0% de las mujeres arrojaron resultados positivos para el trastorno depresivo mayor (PHQ-9). El 54,8% de los hombres y el 62,2% de las mujeres presentaban síntomas indicativos de trastorno de ansiedad generalizada (TAG-7). Ser mujer, tener una discapacidad, sufrir estigmatización y una menor calidad de vida física fueron factores predictivos de la depresión. La edad, la calidad de vida física, la discapacidad (sólo en el caso de los hombres) y la calidad de vida ambiental (sólo en el caso de las mujeres) fueron factores predictivos de la ansiedad. CONCLUSIONES: Se necesitan iniciativas integradas, intersectoriales y con perspectiva de género para responder a los numerosos retos biopsicosociales a los que se enfrentan las personas afectadas.

A web-based survey to map the electromyography practice in Brazil.

BACKGROUND: Detailed information about the electromyography practice in Brazil is largely unavailable. OBJECTIVE: To evaluate where and how electromyography is performed in Brazil, as well as regional disparities and the professional and academic credentials of electromyographers. METHODS: We conducted an internet-based survey of active Brazilian electromyographers. The websites of health insurance companies, professional academies, medical cooperatives, online search engines, and social networks in each Brazilian state were screened and we evaluated the credentials of each electromyographer listed in the Brazilian Federal Medical Board (BFMB) registration website and their online curricula vitae in the Brazilian National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq, in Portuguese). We also evaluated the same parameters in a control group of non-electromyographer neurologists randomly matched by geographical distribution and gender. RESULTS: We found 469 electromyographers (384 neurologists and 85 non-neurologists), with a male predominance. In total, 81.9% were BFMB-certified neurologists, 49.9%, BFMB-certified clinical neurophysiologists, and 10.4%, BFMB-certified physiatrists. Among the non-neurologists, 48.2% were physiatrists. Most electromyographers practiced in states on the Southern and Southeastern regions of Brazil. When adjusted by population, the Federal District and the states of Mato Grosso do Sul and Goiás presented the highest of eletromyographers density. Electromyographers were not more likely to have current/past academic affiliations. CONCLUSION: In Brazil, electromyography is performed predominantly by neurologists, and half of them are BFMB-certified clinical neurophysiologists. The present study highlights regional disparities and may guide government-based initiatives, for instance, to improve the diagnosis of leprosy and the management of neuromuscular disorders within the Brazilian territory.

ANTECEDENTES: Informações detalhadas sobre a prática de eletromiografia no Brasil são em grande parte indisponíveis. OBJETIVO: Avaliar onde e como a eletromiografia é realizada no Brasil, as disparidades regionais, e as credenciais profissionais e acadêmicas dos eletromiografistas. MéTODOS: Realizamos uma enquete via internet de eletromiografistas brasileiros ativos. Foram rastreados sites de operadoras de planos de saúde, academias profissionais médicas, cooperativas médicas, ferramentas de busca online e redes sociais em cada estado brasileiro. Em seguida, avaliamos as credenciais de cada eletromiografista listado no site de registro do Conselho Federal de Medicina (CFM) e seus curricula vitae online no Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). Também avaliamos os mesmos parâmetros em um grupo controle de neurologistas não eletromiografistas pareados aleatoriamente por distribuição geográfica e gênero. RESULTADOS: Encontramos 469 eletromiografistas (384 neurologistas e 85 não neurologistas), com predominância do sexo masculino. Ao todo, 81,9% eram neurologistas com certificação confirmada pelo site do CFM, 49,9%, neurofisiologistas clínicos com certificação confirmada pelo site do CFM, e 10,4%, fisiatras com certificação confirmada pelo mesmo site. Entre os não neurologistas, 48,2% eram fisiatras. A maioria dos eletromiografistas atuava nos estados do Sul e do Sudeste. Quando ajustados pela população, o Distrito Federal e os estados de Mato Grosso do Sul e Goiás apresentaram a maior densidade de eletromiografistas. Os eletromiografistas não eram mais propensos a ter vínculos acadêmicos atuais/passados. CONCLUSãO: No Brasil, a eletromiografia é realizada predominantemente por neurologistas, e metade deles são neurofisiologistas clínicos com certificação confirmada pelo site do CFM. Este estudo destacou as disparidades regionais, e pode orientar ações governamentais para, por exemplo, melhorar o diagnóstico da hanseníase e o manejo das doenças neuromusculares no território brasileiro.

Minimal effective dose of bedaquiline administered orally and activity of a long acting formulation of bedaquiline in the murine model of leprosy.

BACKGROUND: Bedaquiline (BDQ), by targeting the electron transport chain and having a long half-life, is a good candidate to simplify leprosy treatment. Our objectives were to (i) determine the minimal effective dose (MED) of BDQ administered orally, (ii) evaluate the benefit of combining two inhibitors of the respiratory chain, BDQ administered orally and clofazimine (CFZ)) and (iii) evaluate the benefit of an intramuscular injectable long-acting formulation of BDQ (intramuscular BDQ, BDQ-LA IM), in a murine model of leprosy. METHODOLOGY/PRINCIPAL FINDINGS: To determine the MED of BDQ administered orally and the benefit of adding CFZ, 100 four-week-old female nude mice were inoculated in the footpads with 5x103 bacilli of M. leprae strain THAI53. Mice were randomly allocated into: 1 untreated group, 5 groups treated with BDQ administered orally (0.10 to 25 mg/kg), 3 groups treated with CFZ 20 mg/kg alone or combined with BDQ administered orally 0.10 or 0.33 mg/kg, and 1 group treated with rifampicin (RIF) 10 mg/kg. Mice were treated 5 days a week during 24 weeks. To evaluate the benefit of the BDQ-LA IM, 340 four-week-old female swiss mice were inoculated in the footpads with 5x103 to 5x101 bacilli (or 5x100 for the untreated control group) of M. leprae strain THAI53. Mice were randomly allocated into the following 11 groups treated with a single dose (SD) or 3 doses (3D) 24h after the inoculation: 1 untreated group, 2 treated with RIF 10 mg/kg SD or 3D, 8 treated with BDQ administered orally or BDQ-LA IM 2 or 20 mg/kg, SD or 3D. Twelve months later, mice were sacrificed and M. leprae bacilli enumerated in the footpad. All the footpads became negative with BDQ at 3.3 mg/kg. The MED of BDQ administered orally against M. leprae in this model is therefore 3.3 mg/kg. The combination of CFZ and BDQ 10-fold lower than this MED did not significantly increase the bactericidal activity of CFZ. The BDQ-LA IM displayed similar or lower bactericidal activity than the BDQ administered orally. CONCLUSION: We demonstrated that the MED of BDQ administered orally against M. leprae was 3.3 mg/kg in mice and BDQ did not add significantly to the efficacy of CFZ at the doses tested. BDQ-LA IM was similar or less active than BDQ administered orally at equivalent dosing and frequency but should be tested at higher dosing in order to reach equivalent exposure in further experiments.

Type 2 Leprosy Reaction Mimicking Leukocytoclastic Vasculitis in a Postpartum Patient.

ABSTRACT: Leprosy is a disease caused by Mycobacterium leprae that, depending on a patient's baseline susceptibility and immune system function, can present in a wide variety of ways. The host's immune system response to the infection can be cell-mediated or humoral and can be further altered by changes in immune function or treatment. Depending on the time at which a skin biopsy is taken from affected areas, different inflammatory cell types are present, and the histopathology can mimic that of other infectious, autoimmune, or malignant entities, especially when the clinical information provided is vague. We present a case of a 24-year-old Micronesian woman who initially presented immediately postpartum with clinical and histopathological findings suggestive of urticarial vasculitis, but a subsequent biopsy resulted in a diagnosis of erythema nodosum leprosum reaction and borderline multibacillary leprosy. This case illustrates an unusual clinical and histological presentation of M. leprae and highlights the importance of clinical history.

Analysis of socioeconomic condition and bacillary index with respect to the development of Hansen's disease.

Background: Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae or Mycobacterium lepromatosis and mainly affects the skin and peripheral nerves. Although treatable, its early intervention can significantly reduce the occurrence of disability. India accounts for more than half of new cases globally. This study was undertaken to better understand the clinical traits of newly diagnosed cases in a tertiary facility of Western Uttar Pradesh, and a few from Madhya Pradesh and Uttarakhand. Methods: The observational prospective study was carried out on all the newly diagnosed leprosy cases who visited the Outpatient Department of ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Agra, during October 2019-December 2022. After obtaining answers to a prestructured questionnaire with their consent, participants were enrolled in the study and underwent clinical examination and a slit-skin smear test. Results: A total of 56 cases were investigated, and among them, 20 (35.7%) and 36 (64.3%) women and men, respectively, had positive contact with persons affected by leprosy either within family, friends, or neighbors. It is observed that due to the delayed detection of leprosy cases, paucibacillary (PB) patients converted into multibacillary (MB) patients, and the number of MB cases is much higher compared to PB cases. Conclusion: Leprosy instances continue to spread frequently from sick to healthy people indicating continued transmission of leprosy in society. Multidrug therapy in the management of leprosy cases is effective; however, early diagnosis of PB cases is still a challenge and needs to be addressed on priority.

Leprosy - neglected tropical disease in Pygmies inhabiting Central African Republic.

Leprosy is a neglected tropical disease that is still present worldwide despite efforts aimed at elimination of the disease. The BaAka Pygmy community inhabiting rural areas in the Central African Republic is one of the most leprosy-vulnerable populations. The aim of the study was to assess the prevalence of leprosy in the BaAka Pygmy population. People living in the Dzanga Sangha protected area were regularly visited by a mobile clinic in 2019/2020. The diagnosis was based on the clinical manifestation of the disease. Deformations of skin and extremities were assessed. In a 12-month period 26 cases of leprosy were diagnosed and 25 patients received treatment. 24 of those patients were BaAka Pygmies, 10 were women, 7 were children under 15 years old and 8 were diagnosed with grade 2 disability. Presented data shows that leprosy in Dzanga Sangha region is not well controlled due to the high transmission rate. Efforts to diagnose and report new leprosy cases should be intensified.

Beneficial microbes to suppress Vibrio and improve the culture performance of copepod Tigriopus japonicus Mori.

The use of beneficial microbes, i.e., probiotics, to reduce pathogens and promote the performance of the target species is an important management strategy in mariculture. This study aimed to investigate the potential of four microbes, Debaryomyces hansenii, Ruegeria mobilis, Lactobacillus plantarum, and Bacillus subtilis, to suppress Vibrio and increase survival, population growth and digestive enzyme activity (protease, lipase, and amylase) in the harpacticoid copepod, Tigriopus japonicus. Copepod, T. japonicus stock culture with an initial mean density of 50 individual/mL (25 adult male and 25 adult female) was distributed into five treatments (i.e., four experimental and a control, each with four replicates; repeated twice) using 20 beakers (100 mL capacity each). The copepods were fed a mixture of the dinoflagellate Alexandrium tamarense and the diatom Phyaeodactylum tricornutum (3 × 104 cells/mL-1). Each microbe's concentration was adjusted at 108 CFU/mL-1 and applied to the culture condition. D. hansenii, L. plantarum, and B. subtilis all improved the copepods' survival and population growth, likely by including a higher lipase activity (P < 0.05). In contrast, using R. mobilis did not improve the copepod's culture performance compared to control. B. subtilis was the most effective in decreasing the copepod's external and internal Vibrio loading. The probiotic concentrations in the copepod decreased within days during starvation, suggesting that routine re-application of the probiotics would be needed to sustain the microbial populations and the benefits they provide. Our results demonstrated that D. hansenii and B. subtilis are promising probiotics for mass copepod culture as live food for mariculture purposes.

Clinical-epidemiological characteristics and temporal trend of new cases of grade 2 disability leprosy in the state of Maranhão, Brazil, 2011- 2020.

MAIN RESULTS: Out of 2,147 grade 2 disability leprosy cases, the majority were male, of mixed race/skin color, multibacillary and borderline. The São Luís regional health unit showed a falling trend. IMPLICATIONS FOR SERVICES: The results can guide strategies for the leprosy control program in the state, aiming at new approaches towards early diagnosis, treatment and prevention of disabilities. PERSPECTIVES: Further studies are needed, such as spatial distribution of cases and detection rates of leprosy in children under 15 years of age, in order to gain a better understanding of the epidemiological profile of leprosy in Maranhão. OBJECTIVE: to describe the clinical and epidemiological characteristics of new cases of grade 2 disability leprosy and to analyze its trend in the state of Maranhão, from 2011 to 2020. METHODS: this was a descriptive cross-sectional and ecological time-series study, using data from the Notifiable Health Conditions Information System. A descriptive analysis of the event was carried out according to the sociodemographic and clinical-laboratory characteristics of the cases. The temporal trend of event incidence was analyzed using Prais-Winsten regression. RESULTS: of the 2,147 cases, 71.5% were male, 48.9% had up to 8 years of schooling, 66.5% were of mixed race/color, 95.5% had the multibacillary form, 58.8% were borderline, 32.3% had negative bacilloscopy at diagnosis. There was a stationary trend in the state and a falling trend in the São Luís Health Region (annual percentage change = -64.4%; 95% confidence interval: -73.7;-51.9). CONCLUSION: incidence trend was stable in the state of Maranhão and falling in São Luís.

Identification and characterization of endo-α-, exo-α-, and exo-ß-D-arabinofuranosidases degrading lipoarabinomannan and arabinogalactan of mycobacteria.

The cell walls of pathogenic and acidophilic bacteria, such as Mycobacterium tuberculosis and Mycobacterium leprae, contain lipoarabinomannan and arabinogalactan. These components are composed of D-arabinose, the enantiomer of the typical L-arabinose found in plants. The unique glycan structures of mycobacteria contribute to their ability to evade mammalian immune responses. In this study, we identified four enzymes (two GH183 endo-D-arabinanases, GH172 exo-α-D-arabinofuranosidase, and GH116 exo-ß-D-arabinofuranosidase) from Microbacterium arabinogalactanolyticum. These enzymes completely degraded the complex D-arabinan core structure of lipoarabinomannan and arabinogalactan in a concerted manner. Furthermore, through biochemical characterization using synthetic substrates and X-ray crystallography, we elucidated the mechanisms of substrate recognition and anomer-retaining hydrolysis for the α- and ß-D-arabinofuranosidic bonds in both endo- and exo-mode reactions. The discovery of these D-arabinan-degrading enzymes, along with the understanding of their structural basis for substrate specificity, provides valuable resources for investigating the intricate glycan architecture of mycobacterial cell wall polysaccharides and their contribution to pathogenicity.

[Conservative treatment of supination and external rotation for type â ¢ and â £ankle fracture by bone setting].

OBJECTIVE: To explore curative effect of conservative treatment of supination-lateral rotation (SER) with type Ⅲ and Ⅳ ankle fracture by bone setting technique. METHODS: From January 2017 to December 2019, 64 patients diagnosed with SER with type Ⅲ and Ⅳ ankle fracture were treated with manipulative reduction and conservative treatment (manipulation group) and surgical treatment with open reduction and internal fixation (operation group), 32 patients in each group. In manipulation group, there were 17 males and 15 females, aged from 15 to 79 years old with an average of (51.42±13.68) years old;according to Lauge-Hansen classification, there were 8 patients with supination external rotation type Ⅲ and 24 patients with type Ⅳ. In operation group, there were 13 males and 19 females, aged from 18 to 76 years old with an average of (47.36±15.02) years old;7 patients with type Ⅲ and 25 patients with type Ⅳ. Displacement of ankle fracture was measured by Digimizer software, and compared before treatment, 3 and 12 months after treatment between two groups. Lateral medial malleolus displacement, lateral medial malleolus displacement, lateral malleolus displacement, lateral malleolus displacement, lateral malleolus contraction displacement and posterior malleolus displacement were measured and compared between two groups. Mazur score was used to evaluate ankle joint function. RESULTS: All patients were followed up from 12 to 36 months with an average of (17.16±9.36) months. There were statistical differences in lateral medial malleolus displacement, lateral medial malleolus displacement, lateral malleolus displacement, lateral malleolus displacement, lateral malleolus contraction displacement and posterior malleolus displacement in manipulation group before and after reduction(P<0.05). Compared with operation group, there were no statistically significant differences in lateral malleolus shift, lateral malleolus shift, lateral malleolus contraction shift(P>0.05), while there were statistically significant differences in lateral malleolus shift, posterior malleolus shift up and down (P<0.05). Mazur scores of ankle joint at 3 months after treatment in manipulation group and operation group were 68.84±13.08 and 82.53±7.31, respectively, and had statistical differences(P<0.05), while there was no difference in evaluation of clnical effect(P>0.05). There were no differences in Mazur score and evaluation of clnical effect between two groups at 12 months after treatment (P>0.05). CONCLUSION: Bone setting technique could effectively correct lateral displacement of medial malleolus, lateral displacement of medial malleolus, lateral displacement of lateral malleolus and lateral contraction displacement of lateral malleolus in supination lateral rotation type Ⅲ and Ⅳ ankle fracture, and has good long-term clinical effect, which could avoid operation for some patients and restore ankle function after fracture.