Search Results (218)

Metastatic castration-resistant prostate cancer/PCa (mCRPC) is a clinically advanced form of PCa that is associated with increased aggressiveness, cancer stemness, morbidity, and the risk of developing resistance to taxanes, currently the first-line chemotherapy for mCRPC. Clofazimine (CLF) is a potential immunomodulator drug that is FDA-approved for the treatment of leprosy. Recently, using in vitro, in vivo, and ex vivo models, we established the efficacy of CLF in chronic myeloid leukemia and multiple myeloma. Here, we demonstrate that CLF is effective as a single agent and in combination with taxanes in a panel of cell lines representing the diversity of CRPC patients. Using a microfluidic assay, we showed the impact of CLF on cancer cell migration and metastatic potential. Further, we also found that CLF reduces ALDH activity—a marker for cancer ‘stem-like’ cells (CSCs), a subtype of cancer cells with self-renewal and differentiation capacities (epithelial-to-mesenchymal transdifferentiation/EMT). Bulk and single-cell RNAseq followed by functional validation and in silico analysis showed that CLF treatment is associated with apoptosis, ER stress, oxidative phosphorylation, and mitochondrial dysfunction. Most importantly, CLF modulates the expression of several non-coding RNAs, including MALAT1 and NEAT1, that are linked to tumor cell proliferation, cell migration, and drug resistance. Full article

Background: Tuberculosis (TB) constitutes one of the leading causes of morbidity and mortality worldwide. Due to adopted prevention measures, good public health practices, and better treatment, its incidence, prevalence, and case fatality rates steadily fell. Objectives and Methods: Following a case–control research design, this study aimed to explore the risk factors of pulmonary TB among patients registered in the Aseer Region, Saudi Arabia. This study included 105 active TB cases (study group) and 143 (control group) who were randomly recruited from those attending the vaccination units at Primary Healthcare Centers in Aseer. Results: Participants differed significantly according to their nationality (with 65.7% being Saudi in the TB group compared with 89.5% Saudi nationals in the control, p < 0.001); educational status (with 27.6% being university graduates in the TB group compared with 53.8% in the control, p < 0.001); marital status, with most TB patients being single, compared with control (70.5%, and 44.1%, p < 0.001); monthly income, with lower income <5000 Saudi Riyals (SRs), among TB patients than control subjects (80% and 44.1%, p < 0.001); and body mass index (20% of the TB patients were underweight, compared with 6.3% in the control, p < 0.001). Also, participants differed significantly according to their residence, with more rural residence among TB patients than control (18.1% and 7%, p = 0.007), and type of houses, with 84.8% of TB patients living in apartments, compared to 68.5% of the control (p < 0.001). The binary logistic regression model of the possible risk factors related to pulmonary TB revealed that nationality, residence, and body mass index were the only significant independent risk factors (p < 0.001, p = 0.007, and p < 0.001). Conclusions: Personal characteristics of pulmonary TB patients include being non-Saudi, less educated, not married, unemployed, with a low monthly income, and being underweight. Risk factors related to place included residing in rural areas and living in the basement of a rented apartment. Full article

Citrus leprosis (CL) and citrus zonate chlorosis (ZC) were first described in Brazil in the 1930s. Both diseases, which caused non-systemic lesions primarily characterized by chlorotic and/or necrotic spots, were associated with the presence of Brevipalpus mites. While CL has since been well characterized as being caused by viruses of the genera Cilevirus (family Kitaviridae) and Dichorhavirus (family Rhabdoviridae) and transmitted by several species of Brevipalpus mites, the causal agent of ZC remained unknown. In this study, we analyzed Citrus spp. samples exhibiting typical ZC symptoms using high-throughput sequencing (HTS) to determine the etiology of ZC. We examined historical herbarium specimens collected between 1933 and 1965 alongside fresh samples collected from 2016 to 2022. Our results identified the higrevirus hibiscus green spot virus 2 (HGSV2, Higrevirus waimanalo) as the causal agent of ZC. In addition, we report for the first time the presence of a higrevirus in continental America, expand the diversity of known kitaviruses infecting citrus in Brazil, and demonstrate the transmission of an higrevirus by Brevipalpus yothersi and B. papayensis. Full article

Tuberculosis preventive treatment (TPT) is a mainstay for reducing the tuberculosis (TB) burden among people living with human immunodeficiency virus (PLHIV). Context-specific challenges hinder TPT uptake and completion among PLHIV. During 2022–2024, a mixed-methods design was used to evaluate the TPT cascade and explore its facilitators and barriers among PLHIV availing care from 12 PEPFAR-supported health facilities in Uganda. The quantitative component included analysis of routine programmatic data, and the qualitative component included focus group discussions and in-depth interviews with healthcare workers and PLHIV. A total of 1349 PLHIV were enrolled in the evaluation. Among PLHIV newly initiated on ART (≤3 months), 74% started TPT, and 98% of them completed it. In PLHIV already on ART, 87% had initiated TPT (76% before and 11% during this evaluation), with a treatment completion rate of 98%. The facilitators for TPT implementation included access to shorter TPT regimens, integration of services, and adherence counseling. Barriers included knowledge gaps, pill burden, TPT drug stock-outs, and documentation inconsistencies. The TPT completion rate was higher than the national target (90%), but the TPT initiation remains low. Improved access to shorter regimens, adherence counseling, better documentation, and service integration can sustain the completion rate and improve the initiation rate in Uganda and possibly elsewhere. Full article

For drug-susceptible TB, the WHO-endorsed first-line regimen (isoniazid, rifampicin, ethambutol, pyrazinamide) remains the global reference. Therapy must always be tailored to drug susceptibility, especially in MDR- and XDR-TB. HIV-associated mycobacterial infections—including Mycobacterium tuberculosis (TB), disseminated Mycobacterium avium complex (MAC), and Mycobacterium leprae (M. leprae)—remain leading causes of morbidity and mortality in people living with HIV (PLWH). TB continues to account for the highest burden of AIDS-related deaths worldwide, while MAC and leprosy complicate care in advanced immunosuppression. This review synthesizes current evidence on epidemiology, clinical features, and management challenges of HIV–mycobacterial co-infections. We discuss drug-susceptible and drug-resistant TB therapies, drug–drug interactions with antiretroviral therapy (ART), and the clinical impact of immune reconstitution inflammatory syndrome (IRIS). Beyond established regimens, we highlight host-directed strategies such as metformin, glutathione augmentation, mTOR modulation, and vitamin D; immunotherapies including interferon-γ, GM-CSF, and IL-7; and therapeutic vaccines (M72/AS01E, MTBVAC, VPM1002) as promising adjuncts. Distinct from guideline-focused overviews, this review emphasizes non-tuberculous mycobacterial disease (NTM, including MAC) and leprosy in PLWH and synthesizes host-directed and adjunctive strategies with their translational prospects, including ART compatibility and IRIS. By integrating TB, NTM, and leprosy across the HIV care continuum, we highlight opportunities not treated in detail elsewhere—particularly HDT-enabled approaches and implementation considerations in PLWH. Full article

Leprosy is a chronic infectious disease that targets the peripheral nervous system, leading to peripheral neuropathy. Mycobacterium leprae primarily infects Schwann cells, adipocytes, and macrophages, altering their metabolism and gene expression. This study investigates the metabolic interaction between M. leprae and Schwann cells, with a focus on indoleamine 2,3-dioxygenase (IDO), a key enzyme in tryptophan catabolism via the kynurenine pathway. We found that M. leprae induces IDO expression in Schwann cells, suggesting a role in immune modulation and neuropathy. Inhibition of IDO with 1-methyl-L-tryptophan (1-MT) reduced Schwann cell viability and metabolic activity in response to M. leprae. After 24 h of infection, M. leprae impaired mitochondrial membrane potential, although no significant changes in autophagy or mitochondrial ultrastructure were observed by electron microscopy. Interestingly, IDO1 inhibition upregulated the expression of antioxidant genes, including GPX4, NFE2L2, and HMOX1. In conclusion, these findings highlight a central role for IDO in shaping the metabolic and immunological response of Schwann cells to M. leprae infection. IDO induction contributes to immune regulation and cellular stress, while its inhibition disrupts cell viability and promotes antioxidant gene expression. These results position IDO as a potential therapeutic target for modulating host–pathogen interactions and mitigating nerve damage in leprosy. Full article

Leprosy remains a significant public health issue, particularly due to its neuropathic consequences, which affect sensory, motor, and autonomic functions, leading to severe disabilities. HIV/AIDS, another major public health concern, overlaps geographically with leprosy and is also associated with peripheral neuropathies, complicating the management of co-infected patients. Understanding how Nerve Growth Factor (NGF) is regulated in leprosy and HIV-leprosy co-infection may contribute to immunomodulatory treatments and neuroimmune response control. A cross-sectional study evaluated NGF tissue expression using immunohistochemistry in 47 HIV/leprosy co-infected patients and 61 leprosy-only patients. The co-infected group had a higher incidence of neuritis (40.4%) and a prevalence of exclusively reversal reactions. However, the occurrence of neuritis was not associated with higher expression of NGF in the tissue. Leprosy reactions were more prevalent in non-co-infected patients with multibacillary forms (50%). Multibacillary forms in both groups of patients showed higher cellular expression of NGF, with a greater tendency for higher NGF expression in non-co-infected multibacillary patients (p = 0.0021), suggesting impairment in the immune response involved in the tissue expression of neurotrophins in the co-infected group. Overall, co-infection with HIV did not influence the increase in NGF in the lesions of leprosy patients compared with patients with leprosy alone. Full article

Bangladesh is among the 23 WHO priority countries for leprosy, with a new case detection rate of 21 per million population including children among new cases indicating recent transmission. We aimed to compare active versus passive case detection using geospatial tools. A cluster-randomized study was conducted across seven intervention and seven control districts. In the intervention arm, GPS coordinates of new cases were recorded, and contacts within a 75-m buffer were screened. Spatial cluster analysis using Kulldorff’s scan statistics was performed to identify hotspots. The main objective was to achieve early case detection in intervention areas, reflected in a lower proportion of new patients with grade 2 disabilities (G2Ds). A total of 347/382 (90%) index cases were enrolled in the intervention arm, compared to 380/462 (82%) in the control arm. Among household contacts, 7/1482 (5‰) new cases were found in the intervention area and 12/1565 (7.7‰) in the control area. Additionally, 18/25,720 (0.7‰) new cases were detected among neighbor contacts in the intervention arm. G2D proportions were not lower in the intervention arm (15%) than in the comparator arm (11%, p = 0.043). Comparable household contact cases were observed in both arms, with more cases emerging among neighbors in intervention districts. Eight spatial clusters were identified, including 288/844 (34%) index cases, with three significant clusters from 2022 to 2023. Screening within a 75-m buffer detected additional leprosy cases, though fewer than expected due to COVID-19 limitations. Targeting clusters for case detection and prophylaxis could strengthen transmission control efforts. Full article

Background: Erythroblasts have recently been identified as host cells for malarial parasites, revealing a previously underappreciated host–parasite interaction. However, their extremely low abundance in peripheral blood has hindered progress, especially in elucidating the biological significance of parasitized erythroblasts (pEBs) in vivo. Methods: Here, we visualized pEBs in a murine model and established a method to increase their number in peripheral blood by immunizing mice with live Plasmodium yoelii 17XNL, followed by challenge with P. berghei ANKA. Results: Immunized mice were protected from cerebral malaria and survived longer, during which pEBs appeared in circulation and were detected using Giemsa-stained smears. All blood-stage parasite forms were identified within pEBs, including enucleating erythroblasts. Conclusions: This model enables in vivo/ex vivo analysis of pEB biology without bone marrow/spleen isolation, thus lowering technical/ethical barriers for the field. Full article

Leprosy relief efforts were a key part of the Christian mission of salvation in China. During the Anglo-American Protestant overseas missionary movement in the late 19th and early 20th centuries, many missionaries recorded stories about relief work of Chinese female lepers in Without the Camp: The Journal of The Mission to Lepers in India and the East. First, the missionaries portrayed Chinese female lepers as marginalized figures, symbols of moral suffering and victims in need of salvation, reinforcing their religious mission and humanitarian spirit. Second, through the relief and conversion stories, the missionaries appealed to Anglo-American Christianity to participate in the overseas missionary movement and to fund the leprosy relief cause in China. Finally, the missionaries’ stories of converted Chinese women leprosy victims served as discourses for the spread of the gospel and civilization in China. Full article

Background: Hansen’s disease or leprosy is one of the 21 neglected tropical diseases (NTDs). In Ecuador, leprosy is considered eliminated as a public health problem; however, new cases are reported annually. Additionally, Mycobacterium leprae infection was detected in nine-banded armadillos across the country, suggesting a potential zoonotic reservoir. This literature review aims to provide an updated overview of the epidemiological situation of leprosy in Ecuador, identify knowledge gaps, and outline research priorities to support the development of a comprehensive national strategy for achieving zero autochthonous cases. Methods: This article analyses the current situation of leprosy in Ecuador based on international and national publications. A retrospective literature search using five international, regional, and national publications on leprosy published between 1954 and 2024 (70 years) with no restriction on language or publication date, was performed. Findings: Our review identified 28 publications with the earliest article dating back to 1954. Of these, 14 were published in international journals, 15 (53.6%) were in Spanish. Four nationwide studies documented leprosy cases across Ecuador’s three continental regions (Coast, Andes, and Amazon) with a predominance in the tropical coast. No cases have been reported from the Galápagos Islands. From 1983, Ecuador started multi-drug therapy. Data from the Ministry of Public Health (MoH) system identified 1539 incident cases, showing a significant decline in new cases from 2000 to 2024, with no cases in children. New cases detection rate by 100,000 inhabitants was 0.51 in 2019 according to the World Health Organization (WHO). No study has genotyped the Mycobacterium spp. in human cases, other animal species, or environment. According to the MoH, multibacillary leprosy accounts for 78.95% of diagnosed cases, with confirmation based on Ziehl–Neelsen staining and histopathology. No survey has assessed disabilities, knowledge, attitudes, and practices (KAP) or stigma related to leprosy. Research is needed on transmission routes, Mycobacterium genotyping, genetic susceptibility, and antibiotic resistance. BCG vaccination coverage fell to 75.3% in 2021. Cases are currently diagnosed and treated on an outpatient basis in large hospitals. Conclusions: This comprehensive review highlights persistent gaps in leprosy research and critical information, despite seven decades of documented cases in Ecuador. The disease is still endemic across the country, particularly at subnational level in the subtropics and tropics of the Pacific coast and the Amazon. There is a need for nationwide epidemiological research on reservoirs and the environment applying the One Health concept. Increased laboratory facilities and readily available official data are required to improve our understanding of leprosy in Ecuador. Strengthening community-level efforts is essential for Ecuador to meet the targets of the “WHO’s Towards Zero Leprosy: Strategy 2021–2030.” Full article

Background/Objectives: Acne vulgaris is a prevalent dermatological condition, yet clear, region-specific management guidelines, particularly for India’s diverse population, remain limited. Effective acne management extends beyond pharmacologic therapy, emphasizing proper skincare, patient education, and adherence strategies. This consensus aims to provide tailored, evidence-based recommendations for optimizing acne treatment in the Indian context. Methods: A panel of 14 dermatology experts with ≥15 years of experience reviewed literature, real-world clinical practices, and patient-centric factors relevant to acne management in India. Using a modified Delphi process with two virtual voting rounds, 61 statements across seven clinical domains were evaluated. Consensus was defined as ≥75% agreement. Results: Topical retinoids remain the first-line therapy, with combination regimens (benzoyl peroxide or topical antibiotics) preferred to enhance efficacy and minimize antibiotic resistance. Hormonal therapies, including combined oral contraceptives and spironolactone, are recommended for females with resistant acne. Guidance includes individualized treatment plans, baseline investigations, and selection of appropriate topical and systemic agents. Special considerations for pregnancy and lactation prioritize maternal and fetal safety. Conclusions: This expert consensus provides practical, evidence-based recommendations for acne management in India, integrating pharmacological and non-pharmacological approaches. The tailored guidance supports individualized care, antibiotic stewardship, and improved treatment adherence, aiming to enhance patient outcomes nationwide. Full article

Leprosy is a chronically infectious disease caused by infection with Mycobacterium leprae, or the more recently discovered Mycobacterium lepromatosis. In the Americas, wild armadillos of the Dasypus genus are natural hosts. A systematic review evaluated demographics and spatiotemporal patterns of infection with leprosy-causing bacteria in wild populations of the Dasypus novemcinctus species complex. The Web of Science Core Collection, Biosis Citation Index, Dissertations and Theses, and PubMed databases, in addition to Google Scholar, were searched on 16 April 2022. 158 records were recovered, and six peer-reviewed journal articles were selected and summarized that evaluated the effects of M. leprae-infection on mortality, reproduction, age structure, and sex ratio, in addition to seasonal, annual, and spatial infection patterns. Findings indicate that infection with M. leprae has the potential to impact reproduction, mortality, and population age structure. Studies found that the pathogen does not appear to cluster in populations, but consistent temporal findings were not recovered. A limitation of this review is that there was a single reviewer, which may introduce bias. A better understanding of the impacts and distribution of leprosy in wild populations would allow for improved management recommendations for nuisance Dasypus armadillos throughout their range and limit potential zoonotic transmission. Full article

Background: Neuropathic pain (NP), resulting from damage to the somatosensory nervous system, affects 7–10% of the global population and remains poorly managed despite available therapies. Smoking has been associated with increased pain severity and disease burden, yet its role in neuropathy/NP has not been systematically reviewed. This systematic review synthesizes the existing literature on smoking status and its relationship with neuropathy/NP incidence, prevalence, and severity. Methods: The review was conducted in accordance with PRISMA guidelines and included studies that assessed smoking consumption, dependency, quantity, and cessation in individuals with neuropathy/NP. Summary estimates were stratified by exposure type, and pooled odds ratios and relative risks were calculated. Results: Across 62 studies comprising cohort, case–control, and cross-sectional designs, smoking was consistently associated with greater NP prevalence and pain severity. Smoking dependency was linked to increased incidence, while cessation was associated with reduced risk of NP. Despite considerable heterogeneity and risk of bias, particularly from subjective exposure measurement and inconsistent classification, this relationship remained statistically significant. Conclusions: Findings support the role of smoking as a modifiable risk factor in various etiologies of neuropathy/NP. Cessation may represent a low-cost, low-risk, low-tech adjunctive therapy; however, further robust cessation interventional trials are needed, particularly for less common infectious causes of chronic NP such as leprosy. Full article

The emergence and spread of HIV drug resistance mutations (DRMs) pose a threat to current and future treatment options. To inform policy, this review aimed to determine the magnitude and patterns of DRMs in patients on ART in Tanzania. A systematic literature search was conducted in MEDLINE through PubMed, Embase, and CINAHL up to December 2024. A total of 9685 HIV patients from 23 eligible studies were analyzed. The prevalence of virological failure in studies that used a threshold of >1000 and >400 copies/mL was 24.83% (95% CI: 17.85–32.53%) and 36.94% (95% CI: 24.79–50.00%), respectively. Major DRMs were observed at 87.61% (95% CI: 76.25–95.91%). A decrease in prevalence was observed in studies conducted from 2019, with a pooled prevalence of 62.15% (95% CI: 31.57–88.33%). The most frequently observed HIV-1 subtypes were subtype C at 36.20% (95% CI: 30.71–41.85%), A1 at 33.13% (95% CI: 28.23–38.20%), and subtype D at 16.00% (95% CI: 11.41–21.12%), while recombinant forms of the virus were observed at 13.29% (95% CI: 9.79–17.17%). The prevalence of DRMs against NRTIs and NNRTIs was significantly high, while that against INSTIs and PIs was low, supporting the continued use of PI- and INSTI-based regimens in Tanzania and the need for continued surveillance of DRMs. Full article