Leprosy Reactions Research Articles

Robust contact tracing and screening needed for leprosy control and protection of vulnerable children

Leprosy in children is considered as an indicator of active disease transmission in the community. We report about a seven- year-old male from Telangana, India, with anesthetic skin lesions and familial leprosy history. Clinical examination revealed multiple, dry, scaly, hypopigmented, well-defined, raised punched out anesthetic skin lesions all over the body with both ulnar nerves enlarged. On clinical and laboratory examination, the child was diagnosed with borderline-borderline (BB), multibacillary (MB) leprosy, and Type-1 reaction. The child received a weight-adjusted MB multidrug therapy regimen and corticosteroids for type-1 reactions. This case emphasizes the need for contact tracing and screening for early diagnosis of child leprosy to prevent complications like leprosy reactions which are the risk factors for disability.

Unveiling inflammatory biomarkers in multibacillary leprosy: the role of lymphocyte-platelet ratio in predicting leprosy reactions.

Leprosy is a neglected contagious disease that causes physical disability and episodes of inflammation, called leprosy reactions. There are currently no consolidated laboratory markers that can predict or confirm the diagnosis of leprosy reactions, negatively impacting the progression of the disease. The aim of this study was to analyze the behavior of inflammatory biomarkers in a population of patients with multibacillary leprosy. This prospective study in a northeastern capital involved 67 new cases of multibacillary leprosy, assessing inflammatory biomarkers at diagnosis. Histopathology, qPCR, slit skin smear microscopy, and laboratory tests, including CRP-albumin, neutrophil-lymphocyte, lymphocyte-monocyte, platelet-lymphocyte ratios, and systemic immune-inflammation index, were conducted. Statistical analysis utilized Stata version 16.0®, employing Chi-square, Kruskal-Wallis, and Poisson regression (5% significance). The population, mainly young brown men with low socioeconomic status, borderline leprosy, and and degree of physical disability one, saw 19.4% experiencing leprosy reactions. Standard multibacillary multidrug therapy was administered to all. Ratios and index values exceeding medians were prevalent (46.3-47.8%). Assessing biological markers against leprosy reactions revealed a positive relation between reactions and lymphocyte-platelet ratio (p = 0.05) and a positive trend with the systemic immune-inflammation index (p = 0.06). Patients with reactions were 1.3 times more likely to exhibit an elevated lymphocyte-platelet ratio. The lymphocyte-platelet ratio emerged as a potential indicator for recognizing leprosy reactions. Further research is essential to validate these findings, aiming for earlier detection of leprosy reactions.

Profile of Leprosy Patients at the Dermatology and Venereology Polyclinic of Dr. M. Djamil Padang Hospital in 2018-2021

Leprosy is a chronic infectious disease caused by Mycobacterium leprae that attacks several parts of the body, especially the upper respiratory tract, skin, and peripheral nerves. Indonesia is the third country with the most leprosy in the world. This study aims to determine the profile of leprosy patients at the Dermatology and Venereology Polyclinic Dr. M. Djamil Padang Hospital in 2018-2021. This research is descriptive retrospective with total sampling technique using secondary data in the form of medical records. The sample of this study were all leprosy patients in 2018-2021 who were fulfilled inclusion criteria, with a total of 39 patients. The results showed that the most age group was >14 years (100%), the most gender was male (74.36%), the most residence was Padang (33.33%), and almost all leprosy patients (92.31%) had no history of household contact with leprosy patients. Most of the leprosy patients were of the multibacillary type (74.36%) with positive smear results (46.15%), without leprosy reaction (61.54%), and the most disability level that occurred was grade 0 disability (48.72%). The conclusion of this study is that most cases of leprosy at the Dermatology and Venereology Polyclinic RSUP Dr. M. Djamil Padang in 2018-2021 aged >14 years, male, having address in Padang City, had no history household contact, multibacillary type, positive smear result, without reaction, and level 0 disability.

Ulcerative type 1 lepra reaction in borderline-tuberculoid leprosy

Introduction: leprosy is a chronic infectious disease caused by Mycobacterium leprae, characterized by a wide spectrum of clinical presentations. In India, borderline-tuberculoid leprosy is the most common form encountered in clinical practice. Type 1 lepra reaction in borderline- uberculoid leprosy usually presents as the development of erythema and/or edema in pre-existing skin lesions. Ulceration of skin lesions in type 1 lepra reaction is uncommon and occurs in severe reactions. Objective: to report an unusual presentation of borderline-tuberculoid leprosy with ulcerative type 1 lepra reaction in an immunocompetent patient. Case description: we present the case of a 65-yearold man with chief complaints of ulcerated plaque over his left thigh. He also had other skin lesions suggestive of borderline-tuberculoid leprosy over his trunk and limbs, as well asenlarged, mildly tender left ulnar and lateral popliteal nerves. A slit skin smear was negative, while a skin biopsy supported the diagnosis of borderline-tuberculoid leprosy. The patient responded to multibacillary multidrug therapy according recommended by World Health Organization and tapering doses of prednisolone, with complete healing of the ulceration at six weeks follow-up. Discussion: type 1 lepra reaction associated with borderline-tuberculoid leprosy usually presents with increased erythema and edema in pre-existing skin lesions. Ulceration in such skin lesions is not commonly seen except in cases with severe type 1 leprosy reactions. Administration of oral corticosteroids along with multibacillary multidrug therapy is the key to managing ulcerative type 1 lepra reaction. The ulceration heals rapidly with tapering doses of oral corticosteroids, limiting the duration of morbidity. Final consideration: the case emphasizes the need for dermatologists and leprologists to be aware of atypical presentations of leprosy reactions, ensuring timely diagnosis and effective management to achieve optimal patient outcomes.

Substance P- and insulin-like growth factor 1-derived tetrapeptides for neurotrophic keratopathy related to leprosy: a clinical trial

PurposeNeurotrophic keratopathy is part of the leprosy sequelae and causes progressive deterioration of visual acuity. Although leprosy is bacteriologically curable, there is currently no efficient treatment. Eye drops containing tetrapeptides, Phenylalanine-Glycine-Leucine-Methionine-amide (FGLM-NH2) and Serine-Serine-Serine-Arginine (SSSR), derived from substance P and insulin-like growth factor 1 (IGF-1), are clinically efficacious in the treatment of corneal epithelial disorders caused by neurotrophic keratopathy. To further investigate the effect of this treatment on leprosy sequalae, we evaluated the clinical efficacy of FGLM-NH2+SSSR eye drops for treating neurotrophic keratopathy. DesignClinical trial: Interventional, multicenter, exploratory, single-arm, before and after comparison. ParticipantsThe eyes (12) of 11 patients, aged >60 years, were studied from two leprosy sanatoriums in Japan. MethodsPatients with neurotrophic keratopathy in leprosy sanatorium, specifically those with corneal perception of <40 mm, assessed by the Cochet-Bonnet corneal esthesiometer, and persistent corneal epithelial defects (PEDs) and/or corneal stromal thinning were included in this study. Those treated for infection in the acute phase were excluded from the study. Eye drops containing FGLM-NH2 0.05% and SSSR 5x10-6% were administered four times daily for up to 3 months. Fluorescein staining and optical corneal sections were photographed using a slit-lamp microscope at protocol-set intervals. Where possible, anterior segment optical coherence tomography was performed before and after the intervention. Main outcome measuresThe primary outcome measured was improvement in neurotrophic keratopathy. The patient was judged to have improved when one or more of the following criteria were met: 1) healing epithelial defects or 2) increased thickness in the thin area of the cornea. Secondary endpoints were visual acuity, subjective findings, and time to complete healing for a PED. ResultsNeurotrophic keratopathy on epithelial defects or stromal thickness improved in 83.3% of the patients (90% confidence interval 56.2%–97.0%, P<0.00001). The mean value of corrected visual acuity increased -0.16 by logarithm of the minimum angle of resolution. There were no adverse events reported in association with the treatment. ConclusionsWe confirmed that FGLM-NH2+SSSR eye drops are effective for neurotrophic keratopathy without any adverse reaction in leprosy. These results should be disseminated to any parties who could need this information.

A type 1 leprosy reaction in a 50-year-old man.

A type 1 leprosy reaction in a 50-year-old man.

Erythema nodosum leprosum: A pediatric case report successfully treated with thalidomide

We present the case of a 10-year-old patient who visited our hospital with prolonged fever, multiple nodular lesions on the skin, and diagnostic studies that confirmed leprosy. As a complication, there is a type 2 leprosy reaction that does not respond adequately to the use of steroids; therefore, we used thalidomide, a medication that is infrequently used in children. However, we were able to control the inflammatory response.

Implications of drug resistance in leprosy: disease course, reactions and the use of novel drugs.

Leprosy remains a significant neglected tropical disease despite the goal of elimination having been achieved in various endemic nations over the past two decades. Reactional episodes complicate the disease course, resulting in deformities and disability. The main aim of treatment is to kill Mycobacterium leprae and decrease the bacterial load, which could help prevent further bacilli transmission. A major concern in breaking the chain of transmission and possibly for recurrent reactions is the roleof drug-resistant bacilli. Though some data is available on the background prevalence of drug resistance in leprosy, there is a paucity of studies that look for resistance specifically in leprosy reactions. Administration of long-term steroids or immunosuppressants for chronic and recurrent responses in the presence of drug resistance has the twin effect of perpetuating the multiplication of resistant bacilli and encouraging the dissemination of leprosy. The increasing trend of prescribing second-line drugs for leprosy or type 2 reactions without prior assessment of drug resistance can potentially precipitate a severe public health problem as this can promote the development of resistance to second-line drugs as well. A comprehensive multicenter study, including drug resistance surveillance testing in cases of reactions, is necessary, along with the current measures to stop the spread of leprosy. Here, we have detailed the history of drug resistance in leprosy, given pointers on when to suspect drug resistance, described the role of resistance in reactions, methods of resistance testing, and the management of resistant cases with second-line therapy.

Comparative host transcriptomics as a tool to identify candidate biomarkers for immune reactions in leprosy using meta-analysis.

Background Leprosy is no longer considered an imprecation, as an effective multidrug therapy regimen is available worldwide for its cure. However, its diverse clinical manifestations sometimes involve acute inflammatory reactions. These complications result in irreversible nerve damage, neuritis and anatomical deformities that emerge before, during the treatment or after the completion of treatment. Reversal reaction (Type-I) and erythema nodosum leprosum (Type-II) are the leprosy reactions generally seen in patients with lepromatous and borderline forms of leprosy. At present, there is no accurate diagnostic test available to detect these leprosy reactions. Objectives To identify potential biomarkers indicative of Type-I and Type-II leprosy reactions that could help in their early diagnosis. Methods and Results Host-transcriptomics investigations have been utilised in this study to decipher a correlation between host-gene expression-based biomarkers and exacerbation of leprosy reactions. We present a comparative analysis of publicly available host transcriptomics datasets (from Gene Expression Omnibus) related to leprosy reactions. Individual datasets were analysed and integration of results was carried out using meta-analysis. Common differentially expressed genes (DEGs) were identified using the frequentist and Bayesian ratio association test methods. We have identified several genes - ADAMTS5, ADAMTS9, IFITM2, IFITM3, KIRREL, ANK3, CD1E, CTSF, DOCK9 and KRT73 to name a few - which can serve as potential biomarkers for Type-II reaction. Similarly, ACP5, APOC1, CCL17, S100B, SLC11A1 among others may likely serve as biomarkers for Type-I reaction. Limitations The number of datasets related to leprosy reactions found after the systematic search is less (n = 4) and may limit the accuracy of identified biomarker genes. This could be resolved by including more studies in the data analysis. Conclusion We provide a comprehensive list of gene candidates which could be prioritised further in research focusing on immune reactions in leprosy, as they are likely important in understanding its complexities and could be useful in its early diagnosis.

High serum platelet-to-lymphocyte ratio as a risk factor for severe erythema nodosum leprosum

Introduction: Reactions in leprosy occur during the disease's progression and can result in disability. Hematological examination by calculating the platelet-to-lymphocyte ratio (PLR) can potentially predict leprosy reactions, especially erythema nodosum leprosum (ENL). This study aimed to asses the association between high PLR as a risk factor for severe ENL in multibacillary (MB) leprosy patients at Prof. dr. I G. N. G. Ngoerah General Hospital, Denpasar, Bali. Methods: This case-control study uses data from medical records of leprosy patients treated at Prof. dr. I G. N. G. Ngoerah General Hospital from February 2020 to December 2023. The case group comprises MB leprosy patients diagnosed with severe ENL, while the control group consists of MB leprosy patients without ENL. Platelet-to-lymphocyte is calculated by comparing absolute platelet counts with absolute lymphocyte counts from routine blood tests. Data were analyzed using SPSS version 26 by Chi-square test, sensitivity, specificity test and multivariate analysis. Result: A total of 48 subjects included in this study. The analysis results in this study showed that PLR was a risk factor for severe ENL (OR: 4.20; 95%CI: 1.228 - 14.365). Meanwhile, the cut-off point value used to categorize PLR was 151.37, with a sensitivity of 74% and specificity of 58%. Multivariate analysis showed that PLR had an adjusted odds ratio (aOR) of 2.38 (95%CI: 0.39 - 14.54; p= 0.347). Conclusion: High PLR might be associated with an increased risk of severe ENL reactions in MB leprosy patients.

Is there a lack of a glucose monitoring and management protocol for preventing hyperglycemia and glucocorticoid-induced diabetes mellitus in leprosy reactions?

Is there a lack of a glucose monitoring and management protocol for preventing hyperglycemia and glucocorticoid-induced diabetes mellitus in leprosy reactions?

Low serum lymphocyte-to-monocyte ratio as a risk factor for severe erythema nodosum leprosum

Introduction: Leprosy reactions occur during the course of the disease and can lead to disability. Hematologic examination by calculating the lymphocytes-to-monocytes ratio (LMR) is the potential risk factor for leprosy reactions, especially erythema nodosum leprosum (ENL). This study aims to assess the relationship between LMR as a risk factor for severe ENL in multibacillary (MB) leprosy patients at Prof. dr. I G. N. G. Ngoerah Hospital, Denpasar, Bali. Methods: This study used a case-control model with data from the medical records of leprosy patients undergoing treatment at Prof. dr. I G. N. G. Ngoerah Hospital from January 2020 - November 2023. The case group was MB leprosy patients who had been diagnosed with ENL reactions and the control group was MB leprosy patients who did not experience leprosy reactions. Blood serum was taken to analyze the LMR in both groups. Data were analyzed using SPSS version 26. Result: The mean value of LMR in the case group was significantly lower than the case group, 2.67 ± 1.13 versus 3.53 ± 0.96. Meanwhile, the cut-off point value used to categorize LMR was 2.95, with a sensitivity of 75% and specificity of 63.6%. The low LMR odds ratio (OR) was 4.5 (95%CI 1.29-16.76; p=0.015). Multivariate analysis showed low LMR for severe ENL with an adjusted odds ratio (aOR) of 4.080 (95%CI 0.352 - 47.25; p=0.260). Conclusion: Low LMR might be associated with an increased risk of ENL reaction in MB leprosy patients.

Effect of Curcuma longa Extract as Adjuvant Therapy on IL-6 Serum Levels in Leprosy Type 1 Reaction Patients

Type 1 leprosy reaction / Reversal reaction (RR) is an inflammatory episode in existing leprosy lesions and aggravates the pain rate. Long-term therapy with steroids causes a variety of side effects, so an adjuvant therapy alternative is needed to alleviate steroid use. Curcuma longa rhizome extract has become an anti-inflammatory therapy choice in various previous inflammatory diseases. This study aims to determine the anti-inflammatory effect of Curcuma longa rhizome extract as an adjuvant therapy for reversal reaction patients by analyzing serum levels of IL-6 as a marker of inflammation. The pre and post-test randomized single-blinded controlled trial was conducted on two groups, namely control (RR patients with steroid therapy &amp; placebo) and treatment (steroid therapy &amp; Curcuma longa rhizome extract 1 gram/day). IL-6 serum levels were analyzed from sampling before and after the intervention for one month. The serum levels of IL-6 post-test in the control group were significantly higher than those of the pre-test. The treatment group showed lower serum levels of IL-6 post-test compared to pre-test, although there was no significant difference. Curcuma longa rhizome extract 1 gram/day for one month as adjuvant therapy for patients with type 1 leprosy reaction did not significantly reduce serum IL-6 levels.

Correlation between Degree of Leprosy Disability and Serum IL-6 Levels in Patients with Leprosy Reactions: An Observational Study at the Donorojo Jepara Leprosy Hospital Center

Correlation between Degree of Leprosy Disability and Serum IL-6 Levels in Patients with Leprosy Reactions: An Observational Study at the Donorojo Jepara Leprosy Hospital Center

The effect of antireaction medications on the association between periodontitis and leprosy reactions: An important methodological issue in periodontal medicine.

The treatment of leprosy reactions (LRs) involves thalidomide, corticosteroids, and other immunomodulatory medications. This study evaluated the effect of these treatments on the association between periodontitis and LRs, as well as factors associated with LRs. This case-control study was conducted on 283 individuals followed at a leprosy outpatient clinic in Brazil. The case group was comprised of 158 individuals presenting type 1 or type 2 LRs, and the control group of 125 leprosy individuals without reactions. A complete oral examination was performed to diagnose periodontitis, the independent variable. Antireaction medication used was collected from medical records, and participants were classified according to the use of prednisone and/or thalidomide, time of use, or non-use of medication. Socioeconomic-demographic, clinical, and lifestyle covariables were collected by interview. Unconditional logistic regression analysis by subgroups evaluated the effect of antireaction medication on the association between periodontitis and LRs, estimating the odds ratio with a 95% confidence interval (OR; 95% CI). A relationship between periodontitis and LRs was observed only in the subgroup using the association prednisone and thalidomide: ORadjusted=0.32; 95% CI=0.11-0.95. Conversely, more severe periodontal clinical parameters were observed in cases versus controls. Several socioeconomic, health conditions, and lifestyle factors were associated with the presence of LRs. Although periodontal disease indicators were worse among the cases, the findings showed a negative relationship between periodontitis and LRs in individuals receiving associated prednisone and thalidomide. These medications appear to influence the inflammatory cascade between diseases, modifying and masking the manifestations of periodontitis.

The role of monocyte chemoattractant protein-1 (MCP-1) as an immunological marker for patients with leprosy: a systematic literature review

Leprosy, a significant global health concern affecting primarily the peripheral nerves and integumentary system, is influenced by the host immune system’s response, affecting its pathology, disease progression, and reaction occurrence. MCP-1, integral to leprosy’s immunological processes, holds promise as a diagnostic tool and predictor of reaction occurrence. This systematic review aimed to investigate MCP-1’s involvement in leprosy. Literature search, employing specified MeSH keywords, covered databases such as PubMed, Scopus, ScienceDirect, and Wiley Online Library until September 30th, 2023, yielding seventeen relevant studies. Assessing each study’s quality with the Newcastle-Ottawa Scale (NOS) and investigating bias using the Risk of Bias Assessment tool for Non-randomized Studies (RoBANS), a narrative synthesis compiled findings. Seventeen distinct studies were included, each characterized by diverse designs, sample sizes, demographics, and outcome measures, highlighting MCP-1’s potential in diagnosing leprosy, differentiating it from control groups, and discerning leprosy types. Furthermore, MCP-1 shows promise in predicting leprosy reversal reactions. Although MCP-1 offers clinical benefits, including early diagnosis and type differentiation, further research with larger sample sizes and standardized methodologies is imperative to confirm its diagnostic utility fully.

IgG seroprevalence of Toxoplasma gondii and Leishmania infantum in leprosy patients: Implications for screening and management of co-infections

Parasitic co-infections are common in developing countries and can interfere with leprosy treatment, leading to an increased risk of inflammatory leprosy reactions. This study assessed serum immunoglobulin G (IgG) levels against Toxoplasma gondii and Visceral Leishmaniasis (VL) antigens in 270 leprosy patients from Brazilian states. Regarding the respective cut-offs, the prevalence of IgG seropositivity for T. gondii and VL were 21.05 % and 47.36 % in the leprosy-negative group, and 77.7 % and 52.6 % in the leprosy-positive group. Of the 270 leprosy patients, 158 (58.5 %) presented with inflammatory leprosy reactions. Of those, 72 (59.5 %) had neuritis, 35 (48.6 %) had reverse reactions, and 28 (38.9 %) had ENL in both Brazilian states. Leprosy patients with anti-Leishmania IgG seropositivity were 3.25 times more likely to develop neuritis (95 % C.I.: 1.187 - 9.154; p = 0.019). These findings are particularly relevant for clinical settings where both leprosy and parasitic diseases are prevalent and could provide essential guidance for detecting and addressing complications arising from parasitic co-infections in leprosy patients, thereby improving clinical management strategies.

Toxoplasma gondii infection and high levels of IgE are associated to erythema nodosum leprosy (ENL).

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.

Leprosy in Spain: A Descriptive Study of Admissions at Fontilles Sanatorium between 1909 and 2020.

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. 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 (n = 2652). 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. 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.

Metformin as adjunctive therapy in combination with multidrug treatment for multibacillary leprosy: A protocol for a randomized double-blind, controlled Phase 2 trial in Indonesia (MetLep Trial).

The clinical management of leprosy is complicated by leprosy reactions (LR) causing irreversible nerve damage and disabilities. LR often require long-term use of corticosteroids causing serious side effects. Adjunct host-directed therapy (HDT) is a potentially attractive strategy in leprosy to prevent LR and associated immunopathology, modulate immunological memory that protects against recurrence, and thereby reduce nerve damage, disability and corticosteroid-associated morbidities. Metformin, a well-tolerated, safe and cheap anti-hyperglycaemic drug, is repurposed as HDT in auto-immune and infectious diseases, like tuberculosis (TB). Metformin use in people with diabetes is associated with reduced risks of TB-infection, progression to active TB, treatment failure and TB-mortality. Given the similarities both mycobacteria share, we hypothesize that among persons with multibacillary (MB) leprosy, adjunctive metformin may prevent/mitigate LR. We will perform a double-blind controlled proof-of-concept trial in which people with newly diagnosed multibacillary leprosy will be randomized (1:1) to metformin hydrochloride 1000mg extended release once daily versus placebo for 24 weeks in addition to standard-of-care WHO MB multidrug therapy (MDT) during 48 weeks. We aim to enrol 166 participants aged between 18 and 65 years, across five clinical sites in two leprosy endemic areas in Indonesia. Primary outcomes are the proportion of participants experiencing a LR and the frequency of (serious) adverse events. Secondary outcomes are the severity and time to first LR, the cumulative corticosteroid usage, and quality of life. The total study follow-up is 48 weeks. LR signify the most important cause of irreversible nerve damage leading to anatomical deformities and disabilities, imposing a social and financial burden on those affected. Our study aims to evaluate the efficacy, tolerability and safety of adjunct metformin added to MDT in persons with multibacillary leprosy, and explore its effects on clinical and immunological outcomes. NCT05243654 (17/02/2022).