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Chemoprophylaxis of leprosy with rifampicin in contacts of multibacillary patients: study protocol for a randomized controlled trial.

ABSTRACT: BACKGROUND:The annual new-case detection rate for leprosy, while generally stable over the last decade, shows that transmission rates have remained stagnant despite the successful worldwide administration of multidrug therapy since the 1980s. As such, novel control strategies are urgently needed. Focusing on managing leprosy patient contacts, the most susceptible to contracting the disease, has been seen as a potential strategy in limiting the spread of leprosy as shown by a number of recent epidemiological studies. Immunoprophylaxis with Bacillus Calmette-Guérin (BCG) has been seen as an effective preventive measure due to its ability to stimulate the development of cellular immunity which is essential in controlling the disease, especially in its multibacillary (MB) forms. The association of immunoprophylaxis with chemoprophylaxis in a single dose of rifampicin has been shown to be a promising preventive strategy, although a variety of studies have found instances of early case detection just a few months after BCG vaccination. METHODS/DESIGN:The present study is a phase IV chemoprophylactic clinical trial consisting of administration of a single dose of rifampicin in MB leprosy patient contacts under care at the Souza Araújo Outpatient Clinic/FIOCRUZ as part of a randomized (2:1), double-blind, placebo-controlled study. It is comprised of two groups: 1) rifampicin + BCG; and 2) placebo + BCG. DISCUSSION:The aim is to evaluate whether the use of chemoprophylaxis with a single dose of rifampicin in MB leprosy patient contacts prior to the BCG vaccine would be able to prevent the onset of leprosy in those cases that may occur just a few months after vaccination. Contact subclinical infections (polymerase chain reaction) and the immunological parameters (anti-PGL-1, anti-LID-1, and IFN-?) will be evaluated and the results will be compared after 12 months of follow-up. TRIAL REGISTRATION:The Brazilian Registry of Clinical Trials (ReBEC), RBR-69QK5P . Retrospectively registered on 1 June 2017.

SUBMITTER: Dos Santos DS

PROVIDER: S-EPMC5914061 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Chemoprophylaxis of leprosy with rifampicin in contacts of multibacillary patients: study protocol for a randomized controlled trial.

Dos Santos Daiane Santos DS Duppre Nádia Cristina NC Sarno Euzenir Nunes EN Pinheiro Roberta Olmo RO Sales Anna Maria AM Nery José Augusto Da Costa JADC Moraes Milton Ozório MO Camacho Luiz Antônio Bastos LAB

Trials 20180423 1

<h4>Background</h4>The annual new-case detection rate for leprosy, while generally stable over the last decade, shows that transmission rates have remained stagnant despite the successful worldwide administration of multidrug therapy since the 1980s. As such, novel control strategies are urgently needed. Focusing on managing leprosy patient contacts, the most susceptible to contracting the disease, has been seen as a potential strategy in limiting the spread of leprosy as shown by a number of re ...[more]

PMID: 29685164

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Project description:BackgroundLeprosy control is based on early diagnosis and multidrug therapy. For treatment purposes, leprosy patients can be classified as paucibacillary (PB) or multibacillary (MB), according to the number of skin lesions. Studies regarding a uniform treatment regimen (U-MDT) for all leprosy patients have been encouraged by the WHO, rendering disease classification unnecessary.Methodology and findingsAn independent, randomized, controlled clinical trial conducted from 2007 to 2015 in Brazil, compared main outcomes (frequency of reactions, bacilloscopic index trend, disability progression and relapse rates) among MB patients treated with a uniform regimen/U-MDT (dapsone+rifampicin+clofazimine for six months) versus WHO regular-MDT/R-MDT (dapsone+rifampicin+clofazimine for 12 months). A total of 613 newly diagnosed, untreated MB patients with high bacterial load were included. There was no statistically significant difference in Kaplan-Meyer survival function regarding reaction or disability progression among patients in the U-MDT and R-MDT groups, with more than 25% disability progression in both groups. The full mixed effects model adjusted for the bacilloscopic index average trend in time showed no statistically significant difference for the regression coefficient in both groups and for interaction variables that included treatment group. During active follow up, four patients in U-MDT group relapsed representing a relapse rate of 2.6 per 1000 patients per year of active follow up (95% CI [0·81, 6·2] per 1000). During passive follow up three patients relapsed in U-MDT and one in R-MTD. As this period corresponds to passive follow up, sensitivity analysis estimated the relapse rate for the entire follow up period between 2·9- and 4·5 per 1000 people per year.ConclusionOur results on the first randomized and controlled study on U-MDT together with the results from three previous studies performed in China, India and Bangladesh, support the hypothesis that UMDT is an acceptable option to be adopted in endemic countries to treat leprosy patients in the field worldwide.Trial registrationClinicalTrials.gov: NCT00669643.

Project description:BackgroundLeprosy is an ancient infectious disease with an annual global incidence of around 200,000 over the past decade. Since 2018, the World Health Organization (WHO) recommends single-dose rifampicin as post-exposure prophylaxis (SDR-PEP) for contacts of leprosy patients. The Post ExpOsure Prophylaxis for Leprosy (PEOPLE) trial evaluated PEP with a double dose of rifampicin in Comoros and Madagascar. Preliminary results of this trial show some reduction in leprosy incidence in intervention villages but a stronger regimen may be beneficial. The objective of the current Bedaquiline Enhanced ExpOsure Prophylaxis for LEprosy trial (BE-PEOPLE) is to explore effectiveness of a combination of bedaquiline and rifampicin as PEP.MethodsBE-PEOPLE is a cluster-randomized trial in which 44 clusters in Comoros will be randomized to two study arms. Door-to-door screening will be conducted annually during four years, leprosy patients identified will be offered standard of care treatment. Based on study arm, contacts aged five years and above and living within a 100-meter radius of an index case will either receive bedaquiline (400-800 mg) and rifampicin (150-600 mg) or only rifampicin (150-600 mg). Contacts aged two to four years will receive rifampicin only. Household contacts randomized to the bedaquiline plus rifampicin arm will receive a second dose four weeks later. Incidence rate ratios of leprosy comparing contacts who received either of the PEP regimens will be the primary outcome. We will monitor resistance to rifampicin and/or bedaquiline through molecular surveillance in all incident tuberculosis and leprosy patients nationwide. At the end of the study, we will assess anti-M. leprae PGL-I IgM seropositivity as a proxy for the population burden of M. leprae infection in 8 villages (17,000 individuals) that were surveyed earlier as part of the PEOPLE trial.DiscussionThe COLEP trial on PEP in Bangladesh documented a reduction of 57% in incidence of leprosy among contacts treated with SDR-PEP after two years, which led to the WHO recommendation of SDR-PEP. Preliminary results of the PEOPLE trial show a lesser reduction in incidence. The BE-PEOPLE trial will explore whether reinforcing SDR-PEP with bedaquiline increases effectiveness and more rapidly reduces the incidence of leprosy, compared to SDR-PEP alone.Trial registrationNCT05597280. Protocol version 5.0 on 28 October 2022.

Project description:BackgroundLeprosy is a chronic infectious disease caused by Mycobacterium leprae, predominantly affecting the peripheral nerves, resulting in sensory and motor deficits in the feet. Foot ulcers and imbalances are frequent manifestations in leprosy, often correlating with diminished sensitivity. While clinical scales and monofilament esthesiometers are conventionally utilized to evaluate foot sensitivity and balance in these patients, their discriminatory power is limited and their effectiveness is greatly dependent on the examiner's proficiency. In contrast, baropodometry and posturography offer a more comprehensive evaluation, aiming to preempt potential damage events. This study aimed was to assess the correlation between baropodometry and force plate measurements in leprosy patients and control participants, to improve the prevention and treatment of foot ulcers and complications associated with leprosy.MethodologyThis cross-sectional study was conducted during 2022 and enrolled 39 participants (22 patients with multibacillary leprosy and 17 non-leprosy controls). Demographic data were collected, and a monofilament esthesiometer was used to assess sensory deficits. In addition, physical examinations and balance and plantar pressure tests were conducted. The Student's t-test was used to compare mean and maximum plantar pressures between groups. For most COP variables, a Mann-Whitney Wilcoxon test was used, except for AP amplitude which was analyzed with the Student's t-test due to its normal distribution. The relationship between foot pressure and balance control was assessed using Spearman's correlation, focusing on areas with significant pressure differences between groups.Principal findingsLeprosy patients showed increased pressure in forefoot areas (T1, M1, T2-T5, and M2) and decreased pressure in hindfoot regions (MH and LH) compared to controls. These patients also displayed higher AP and ML amplitudes, suggesting poorer COP control. Correlation analyses between the two groups revealed that foot plantar pressures significantly impact balance control. Specifically, increased T1 region pressures correlated with greater sway in balance tasks, while decreased MH region pressures were linked to reduced COP control.Conclusions/significanceThe findings suggest a joint disturbance of plantar pressure distribution and static balance control in leprosy patients. These alterations may increase the risk of tissue injuries, including calluses and deformities, as well as falls.

Project description:BackgroundThe ILEP Nerve Function Impairment in Reaction (INFIR) is a cohort study designed to identify predictors of reactions and nerve function impairment in leprosy. The aim was to study correlations between clinical and histological diagnosis of reactions.Methodology/principal findingsThree hundred and three newly diagnosed patients with World Health Organization multibacillary (MB) leprosy from two centres in India were enrolled in the study. Skin biopsies taken at enrolment were assessed using a standardised proforma to collect data on the histological diagnosis of leprosy, leprosy reactions and the certainty level of the diagnosis. The pathologist diagnosed definite or probable Type 1 Reactions (T1R) in 113 of 265 biopsies from patients at risk of developing reactions whereas clinicians diagnosed skin only reactions in 39 patients and 19 with skin and nerve involvement. Patients with Borderline Tuberculoid (BT) leprosy had a clinical diagnosis rate of reactions of 43% and a histological diagnosis rate of 61%; for patients with Borderline Lepromatous (BL) leprosy the clinical and histological diagnosis rates were 53.7% and 46.2% respectively. The sensitivity and specificity of clinical diagnosis for T1R was 53.1% and 61.9% for BT patients and 61.1% and 71.0% for BL patients. Erythema Nodosum Leprosum (ENL) was diagnosed clinically in two patients but histologically in 13 patients. The Ridley-Jopling classification of patients (n = 303) was 42.8% BT, 27.4% BL, 9.4% Lepromatous Leprosy (LL), 13.0% Indeterminate and 7.4% with non-specific inflammation. This data shows that MB classification is very heterogeneous and encompasses patients with no detectable bacteria and high immunological activity through to patients with high bacterial loads.Conclusions/significanceLeprosy reactions may be under-diagnosed by clinicians and increasing biopsy rates would help in the diagnosis of reactions. Future studies should look at sub-clinical T1R and ENL and whether they have impact on clinical outcomes.

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Chemoprophylaxis of leprosy with rifampicin in contacts of multibacillary patients: study protocol for a randomized controlled trial.

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Chemoprophylaxis of leprosy with rifampicin in contacts of multibacillary patients: study protocol for a randomized controlled trial.

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