Pressure Stockings for Edematous Feet in the Lepra Reaction: An Inexpensive Patronage.

Leprosy has been known for its wide range of peripheral nerve and tissue involvement and causing disabilities. Early diagnosis and treatment with multi-drug therapy can save lives and limbs and prevent disabilities. However, management and drug therapy are usually lengthy and full of ups and downs of side effects. Further, the lepra reaction is frequently noted during management, requiring immunosuppression and leading to associated side effects. Limb edema per se due to leprosy is unusual and mostly a symptom of a reactional state. There is no specific management for edema in such cases, and it subsides with improving reactionary states. Nevertheless, the edema may be persistent and bothersome. The present report highlights one such unusual case in a 40-year-old man, diagnosed with borderline-tuberculoid leprosy and experiencing a type-1 reaction. Owing to ocular complications, steroid therapy for the reaction was tapered abruptly, and his limb edema did not subside with the improving lepra reaction. Compression stockings helped to manage edema. This case also makes us ponder the possible use of compression stockings as an opioid-sparing aid in lepra reaction-related edema.

Leprosy: Comprehensive insights into pathology, immunology, and cutting-edge treatment strategies, integrating nanoparticles and ethnomedicinal plants.

Mycobacterium leprae is the causative agent responsible for the chronic disease known as leprosy. This condition is characterized by dermal involvement, often leading to peripheral nerve damage, sensory-motor loss, and related abnormalities. Both innate and acquired immunological responses play a role in the disease, and even in individuals with lepromatous leprosy, there can be a transient increase in T cell immunity during lepromatous reactions. Diagnosing of early-stage leprosy poses significant challenges. In this context, nanoparticles have emerged as a promising avenue for addressing various crucial issues related to leprosy. These include combatting drug resistance, mitigating adverse effects of conventional medications, and enhancing targeted drug delivery. This review serves as a comprehensive compilation, encompassing aspects of pathology, immunology, and adverse effects of multidrug delivery systems in the context of leprosy treatment. Furthermore, the review underscores the significance of ethnomedicinal plants, bioactive secondary metabolites, and nanotherapeutics in the management of leprosy. It emphasizes the potential to bridge the gap between existing literature and ongoing research efforts, with a profound scope for validating traditional claims, developing herbal medicines, and formulating nanoscale drug delivery systems that are safe, effective, and widely accepted.

Temporal trends and space-time distribution of leprosy relapse in Brazil from 2001 to 2021.

BACKGROUND: To analyse the temporal trends and spatiotemporal distribution of leprosy relapse in Brazil from 2001 to 2021. METHODS: An ecological study with a temporal trend approach and space-time analysis of leprosy relapse in Brazil was carried out with data from the Notifiable Diseases Information System. RESULTS: A total of 31 334 patients who experienced leprosy relapse were identified. The number of recurrent cases tended to increase throughout the study period, and this increase was significant among females and in almost all age groups, except for those <15, 50-59 and ≥70 y. Several clusters of high- and low-risk patients were identified across all regions with a heterogeneous distribution. CONCLUSIONS: The burden of relapse showed an increasing trend in some groups and was distributed in all regions.

Hansen's Disease: A Practical Update on a Neglected Globally Significant Infection.

Leprosy is a great mimicker. It is caused by Mycobacterium leprae and Mycobacterium lepromatosis, together termed the M. leprae complex. Leprosy can result in systemic manifestations; however, the neurocutaneous syndrome is the most classic. There is a gap in recognizing the condition leading to misdiagnosis and delays in treatment. Leprosy remains an important cause of aesthetic and functional impairment. In this paper, we provide a practical review of leprosy touching on pathophysiology, clinical manifestation, classification, diagnostic approach and management of the condition in a way that can translate into clinical practice and help physicians better identify and manage potential cases of leprosy.

A challenging case of borderline lepromatous leprosy non-responsive to WHO-MDT: exploring approaches beyond WHO-MDT.

Just as we prioritize personalized medicine for various other medical conditions, we should also include a neglected disease like leprosy, ensuring that patients receive the best care possible and improving their quality of life. Our case highlights the importance of instituting an alternate therapeutic regimen in a scenario where there is a lack of clinical response to multidrug therapy, even in the absence of documented drug resistance of the currently available molecular diagnostics. The search for the perfect regimen tailored for each individual leprosy patient should continue. Alternate anti-leprosy therapy is highly useful in cases with confirmed drug resistance or clinically non-responsive cases; however, their misuse should also be strictly avoided to prevent the development of resistance to them.

Erythema Nodosum Leprosum Reaction Masquerading as Rheumatoid Arthritis.

Erythema nodosum leprosum is a type 3 hypersensitivity reaction that often presents with transient eruptions of red papules, plaques, and nodules. A 52-year-old female presented with multiple joint pain that was being treated as rheumatoid arthritis (RA), but through clinical examination, she was found to have Hansen's disease with a type 2 reaction. Hence, the importance of a thorough clinical examination is a must for the timely and correct diagnosis of patients suffering from Hansen's disease.

Body map stories from Colombia: experiences of people affected by leprosy and the influence of peers during diagnosis and treatment.

INTRODUCTION: Almost one third of people affected by leprosy in Colombia suffer from disability, which often results from delayed diagnosis and treatment. We aimed to explore the experience of people affected by leprosy during the process of diagnosis and treatment and if and how this experience was influenced by peers. METHODS: A qualitative study using body map stories was conducted from October 2019 to February 2020 in Colombia. Adult people affected by leprosy were recruited through patient associations in different cities. We conducted three sessions with an average duration of 2-3 h per participant, during which the participants created a painted map of their body and chose symbols to represent their experience, while being engaged in an informal interview. The sessions were audio recorded, transcribed verbatim and analyzed thematically by an interdisciplinary team, consisting of physicians, social workers and a person affected by leprosy. RESULTS: The 17 study participants (11 female) were aged 20 to 70 years. Leprosy-related manifestations ranged from no to advanced disability. Some participants were active members of associations for people affected by leprosy. Three main themes were identified during analysis: (1) A long pathway to diagnosis, (2) Therapy as a double-edged sword and (3) The influence of other people affected by leprosy. The participants described an often years-long process until being diagnosed, which was marked by insecurities, repeated misdiagnosis, and worsening mental and physical health. Delayed diagnosis was related to late health care seeking, but also to inadequate health communication, lack of leprosy-related knowledge and negligence among health care workers. A high desire to cure motivated the participants to take their medication rigorously, despite the high treatment burden. Support from peers, either within the own social environment or provided from associations, contributed to a faster diagnosis and increased therapy adherence. Peers helped to recognize the symptoms, urged patients to seek care, recommended physicians with leprosy-related knowledge and provided a realistic example of both disease severity and curability. CONCLUSION: People affected by leprosy experience a significant burden during the process of diagnosis and treatment. Involving well-trained peers could foster early diagnosis, treatment compliance and prevention of disability.

Scrutinising delay in leprosy diagnosis in Colombia: perceptions and experiences by leprosy health professionals.

Leprosy is an infectious neglected tropical disease, which can cause irreversible disabilities if not diagnosed in time. Colombia continues to show high rates of leprosy-related disability, mainly due to a delay in diagnosis. Limited knowledge is available that explains this delay, therefore our study aimed to explore the perceptions and experiences of leprosy health professionals with the delay in leprosy diagnosis in the Cesar and Valle del Cauca departments, Colombia. Nine semi-structured expert interviews with leprosy health professionals were conducted in May-June 2023 in Colombia. Thematic analysis was performed to analyse the interview results. Our analysis highlighted that the main reasons for delay at the health system-level included accessibility issues to obtain a diagnosis, lack of expertise by health staff, and barriers related to the organisation of the care pathway. Individual - and community-level factors included a lack of leprosy awareness among the general population and leprosy-related stigma. Diagnostic delay consists of a fluid interplay of various factors. Structural changes within the health system, such as organising integral leprosy care centres and highlighting leprosy in the medical curriculum, as well as awareness-related interventions among the general population, might help reducing diagnostic delays.

Community-Based Intervention for Active Detection and Provision of Single-Dose Rifampicin Post-Exposure Prophylaxis to Household Contacts of Leprosy in Bolivia.

BACKGROUND: To achieve zero leprosy cases in Santa Cruz, Bolivia, we designed a community-based active detection and provision of single-dose rifampicin post-exposure prophylaxis (SDR-PEP) to household contacts with new leprosy patients. METHODS: From July to August 2021, we assessed the current knowledge, attitude, and practices through structured interviews and focus group discussions with community representatives and health staff. This was followed by sensitization sessions, the training of health staff, and the reinforcement of referral mechanisms. Teams, including health staff and community volunteers, visited all new leprosy patients detected in 2021-2023 and household contacts. RESULTS: Among 115 community representatives, knowledge about leprosy etiology was attributed to non-biological factors (74%); fear accounted for 77%, and access to care was perceived as weak (74%), but the outlook was improved by SDR-PEP (80%). Among the 217 health staff interviewed, the programmatic barriers identified were a lack of referral feedback (67%), limited supplies for diagnosis and prevention, and ineffective training (64%). We visited 70 new patients and 258 household contacts. The median age in household contacts was 25 years old; 49% were women, 98% were eligible for SDR-PEP, and all who were eligible accepted it. Those who were non-eligible included one tuberculosis patient and six newly detected leprosy patients (23‱). CONCLUSIONS: A community-based intervention was successful in Santa Cruz, Bolivia. Misbeliefs and a lack of knowledge were identified as barriers. Programmatic components should be reinforced for SDR-PEP extension.

Bartonella henselae DNA detection in patients with type 1 leprosy reactions for more than six months.

Leprosy reactions are among the main causes of physical disability resulting from an infectious disease and can culminate in irreversible physical disabilities, therefore they should be considered a clinical emergency, as well as the elucidation of its cause. Co-infections are considered one of the main triggering causes of leprosy reactions, aggravating and maintaining these reactions for longer in these patients. After reporting a high rate of Bartonella henselae infection in patients with chronic type 2 leprosy reaction, 19/47 (40.4 %) compared to the control group, 9/50 (18.0 %), p = 0.0149, we conducted this study to observe the rate of infection by Bartonella sp. in a group of patients with chronic type 1 leprosy reactions. Blood samples from 14 patients with chronic type 1 leprosy reactions were analyzed by molecular and microbiological tests and compared. The results showed that, like patients with chronic type 2 leprosy reactions, this group of patients has a high proportion of B. henselae infection 6/14 (42.9 %), p = 0.88. We conclude that these bacteria can trigger chronic leprosy reactions and should be investigated in all chronic leprosy reactions patients. Summary Line: Our results showed that, like patients with chronic type 2 leprosy reactions, this group of patients has the same proportion of B. henselae DNA detection 6/14 (42.9 %), p = 0.88.

Late relapses in leprosy patients in Brazil: 10-year post-trial of uniform multidrug therapy (U-MDT/CT-BR).

BACKGROUND: Leprosy is a neglected dermato-neurologic, infectious disease caused by Mycobacterium leprae or M. lepromatosis. Leprosy is treatable and curable by multidrug therapy/MDT, consisting of 12 months rifampicin, dapsone and clofazimine for multibacillary/MB patients and for 6 months for paucibacillary/PB patients. The relapse rate is considered a crucial treatment outcome. A randomized Controlled Clinical Trial (U-MDT/CT-BR) conducted from 2007‒2012 compared clinical outcomes in MB patients after 12 months regular MDT/R-MDT and 6 months uniform MDT/U-MDT in two highly endemic Brazilian areas. OBJECTIVES: To estimate the 10 years relapse rate of MB patients treated with 6 months U-MDT. METHODS: The statistical analyses treated the data as a case-control study, sampled from the cohort generated for the randomized trial. Analyses estimated univariate odds ratio and applied logistic regression for multivariate analysis, controlling the confounding variables. RESULTS: The overall relapse rate was 4.08 %: 4.95 % (16 out of 323) in the U-MDT group and 3.10 % (9 out of 290) in the regular/R-MDT group. The difference in relapse proportion between U-MDT and R-MDT groups was 1.85 %, not statistically significant (Odds Ratio = 1.63, 95 % CI 0.71 to 3.74). However, misdiagnosis of relapses, may have introduced bias, underestimating the force of the association represented by the odds ratio. CONCLUSIONS: The relapse estimate of 10 years follow-up study of the first randomized, controlled study on U-MDT/CT-BR was similar to the R-MDT group, supporting strong evidence that 6 months U-MDT for MB patients is an acceptable option to be adopted by leprosy endemic countries worldwide. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00669643.

Ancient Mycobacterium leprae genome reveals medieval English red squirrels as animal leprosy host.

Leprosy, one of the oldest recorded diseases in human history, remains prevalent in Asia, Africa, and South America, with over 200,000 cases every year.1,2 Although ancient DNA (aDNA) approaches on the major causative agent, Mycobacterium leprae, have elucidated the disease's evolutionary history,3,4,5 the role of animal hosts and interspecies transmission in the past remains unexplored. Research has uncovered relationships between medieval strains isolated from archaeological human remains and modern animal hosts such as the red squirrel in England.6,7 However, the time frame, distribution, and direction of transmissions remains unknown. Here, we studied 25 human and 12 squirrel samples from two archaeological sites in Winchester, a medieval English city well known for its leprosarium and connections to the fur trade. We reconstructed four medieval M. leprae genomes, including one from a red squirrel, at a 2.2-fold average coverage. Our analysis revealed a phylogenetic placement of all strains on branch 3 as well as a close relationship between the squirrel strain and one newly reconstructed medieval human strain. In particular, the medieval squirrel strain is more closely related to some medieval human strains from Winchester than to modern red squirrel strains from England, indicating a yet-undetected circulation of M. leprae in non-human hosts in the Middle Ages. Our study represents the first One Health approach for M. leprae in archaeology, which is centered around a medieval animal host strain, and highlights the future capability of such approaches to understand the disease's zoonotic past and current potential.

Comorbidities and Complications in People Admitted for Leprosy in Spain, 1997-2021.

This study aims to describe the epidemiological and clinical characteristics and trends of these admissions in Spain. This retrospective study drew data from the Hospital Discharge Records Database of the Spanish National Health System. We used the diagnostic codes for leprosy from the International Classification of Diseases, ninth and tenth revisions, to retrieve leprosy admissions from 1997 to 2021. There were 1387 hospitalizations for leprosy The number of annual cases decreased gradually, from 341 cases in 1997-2001 to 232 in 2017-2021 (p < 0.001). Patients' median age increased, from 65 years in 1997-2001 to 76 years in 2017-2021 (p < 0.001), as did the prevalence of some comorbidities, such as hypertension (15% in 1997-2001 to 27.6% in 2017-2021; p < 0.001). The mortality rate (6%) and the frequency of leprosy complications remained stable. After Spain (79.1%), the most common country of origin was Paraguay (4.4%). Admissions decreased significantly in Andalusia, from 42% in 1997-2001 to 10.8% in 2017-2021 (p < 0.001), and in the Canary Islands, from 7.9% in 1997-2001 to 2.6% in 2017-2021 (p = 0.001), whereas they increased in Madrid, from 5.9% in 1997-2001 to 12.1% in 2017-2021 (p = 0.005). Overall, leprosy admissions in Spain have declined, even in the regions with the highest prevalence. Patients admitted for leprosy have become older and sicker.

A recombinant chimeric antigen constructed with B-cell epitopes from Mycobacterium leprae hypothetical proteins is effective for the diagnosis of leprosy.

The diagnosis if leprosy is difficult, as it requires clinical expertise and sensitive laboratory tests. In this study, we develop a serological test for leprosy by using bioinformatics tools to identify specific B-cell epitopes from Mycobacterium leprae hypothetical proteins, which were used to construct a recombinant chimeric protein, M1. The synthetic peptides were obtained and showed good reactivity to detect leprosy patients, although the M1 chimera have showed sensitivity (Se) and specificity (Sp) values higher than 90.0% to diagnose both paucibacillary (PB) and multibacillary (MB) leprosy patients, but not those developing tegumentary or visceral leishmaniasis, tuberculosis, Chagas disease, malaria, histoplasmosis and aspergillosis, in ELISA experiments. Using sera from household contacts, values for Se and Sp were 100% and 65.3%, respectively. In conclusion, our proof-of-concept study has generated data that suggest that a new recombinant protein could be developed into a diagnostic antigen for leprosy.

Whole blood transcriptomics reveals the enrichment of neutrophil activation pathways during erythema nodosum leprosum reaction.

Introduction: Patients with the multibacillary form of leprosy can develop reactional episodes of acute inflammation, known as erythema nodosum leprosum (ENL), which are characterized by the appearance of painful cutaneous nodules and systemic symptoms. Neutrophils have been recognized to play a role in the pathogenesis of ENL, and recent global transcriptomic analysis revealed neutrophil-related processes as a signature of ENL skin lesions. Methods: In this study, we expanded this analysis to the blood compartment, comparing whole blood transcriptomics of patients with non-reactional lepromatous leprosy at diagnosis (LL, n=7) and patients with ENL before administration of anti-reactional treatment (ENL, n=15). Furthermore, a follow-up study was performed with patients experiencing an ENL episode at the time of diagnosis and after 7 days of thalidomide treatment (THAL, n=10). Validation in an independent cohort (ENL=8; LL=7) was performed by RT-qPCR. Results: An enrichment of neutrophil activation and degranulation-related genes was observed in the ENL group, with the gene for the neutrophil activation marker CD177 being the most enriched gene of ENL episode when compared to its expression in the LL group. A more pro-inflammatory transcriptome was also observed, with increased expression of genes related to innate immunity. Validation in an independent cohort indicated that S100A8 expression could discriminate ENL from LL. Supernatants of blood cells stimulated in vitro with Mycobacterium leprae sonicate showed higher levels of CD177 compared to the level of untreated cells, indicating that the leprosy bacillus can activate neutrophils expressing CD177. Of note, suggestive higher CD177 protein levels were found in the sera of patients with severe/moderate ENL episodes when compared with patients with mild episodes and LL patients, highlighting CD177 as a potential systemic marker of ENL severity that deserves future confirmation. Furthermore, a follow-up study was performed with patients at the time of ENL diagnosis and after 7 days of thalidomide treatment (THAL, n=10). Enrichment of neutrophil pathways was sustained in the transcriptomic profile of patients undergoing treatment; however, important immune targets that might be relevant to the effect of thalidomide at a systemic level, particularly NLRP6 and IL5RA, were revealed. Discussion: In conclusion, our study reinforces the key role played by neutrophils in ENL pathogenesis and shed lights on potential diagnostic candidates and novel therapeutic targets that could benefit patients with leprosy.

Spatial-temporal trends in leprosy burden and its associations with socioeconomic and physical geographic factors: results from the Global Burden of Disease Study 2019.

OBJECTIVES: The purpose of our study was to assess the multiscalar changes in leprosy burden and its associated risk factors over the last three decades. STUDY DESIGN: We conducted an in-depth examination of leprosy's spatial-temporal trends at multiple geographical scale (global, regional, and national), utilizing information from Global Burden of Disease, Injuries, and Risk Factors Study (GBD 2019). METHODS: Incidence and the estimated annual percentage change (EAPC) in age-standardized incidence rate (ASIR) of leprosy were determined, with countries categorized based on leprosy incidence changes. We examined socioeconomic and physical geography influences on leprosy incidence via Spearman correlation analysis, using ternary phase diagrams to reveal the synergetic effects on leprosy occurrence. RESULTS: Globally, incident cases of leprosy decreased by 27.86% from 1990 to 2019, with a reduction in ASIR (EAPC = -2.53), yet trends were not homogeneous across regions. ASIR and EAPC correlated positively with sociodemographic index (SDI), and an ASIR growth appeared in high SDI region (EAPC = 3.07). Leprosy burden was chiefly distributed in Tropical Latin America, Oceania, Central Sub-Saharan Africa, and South Asia. Negative correlations were detected between the incidence of leprosy and factors of SDI, GDP per capita, urban population to total population, and precipitation, whereas the number of refugee population, temperature, and elevation showed opposite positive results. CONCLUSIONS: Despite a global decline in leprosy over the past three decades, the disparities of disease occurrence at regional and national scales still persisted. Socioeconomic and physical geographic factors posed an obvious influence on the transmission risk of leprosy. The persistence and regional fluctuations of leprosy incidence necessitate the ongoing dynamic and multilayered control strategies worldwide in combating this ancient disease.