Clinical Research Directory

Accuracy of the Polymerase Chain Reaction of Ulnar Perineural Subcutaneous Aspirate Guided by Ultrasound for the Diagnosis and Monitoring of Leprosy Cure

\*\*Brief Summary\*\* Leprosy is a chronic granulomatous infectious disease caused by \*Mycobacterium leprae\* or \*Mycobacterium lepromatosis\*, characterized by peripheral nerve involvement that may lead to progressive neurological damage, disability, and deformities if not diagnosed and treated early. The diagnosis of leprosy is primarily clinical and epidemiological, supported by laboratory methods such as bacilloscopy and biopsy; however, these tests have limited sensitivity, particularly due to the bacillus' tropism for peripheral nerve structures. Ultrasonography has emerged as a non-invasive imaging method capable of detecting morphological changes in peripheral nerves, including nerve enlargement, fascicular abnormalities, and inflammatory hypervascularization. Despite its diagnostic value, ultrasonography alone cannot detect the presence of the bacillus. This prospective cohort study aims to evaluate the diagnostic and prognostic accuracy of combining clinical evaluation, peripheral nerve ultrasonography, and molecular detection techniques using subcutaneous perineural aspirate. Patients with suspected leprosy attending the Leprosy Outpatient Clinic at the University Hospital of Brasília will undergo clinical evaluation, ultrasound examination of the ulnar nerves, and ultrasound-guided subcutaneous perineural aspirate for molecular detection of \*Mycobacterium leprae\* DNA and RNA using real-time PCR and RT-PCR. Participants will be followed for one year, with assessments performed at diagnosis and after one year of treatment. The study will compare clinical, imaging, and molecular findings to determine whether perineural subcutaneous aspirate combined with ultrasonography improves early detection and diagnostic accuracy compared with conventional methods such as bacilloscopy and biopsy. The study aims to contribute to improved diagnostic strategies for leprosy, enabling earlier detection of neural involvement and potentially reducing disease transmission and long-term disability.

Early Detection and AI-Based Management of Skin-Related Neglected Tropical Diseases in Sub-Saharan Africa by Frontline Health Workers

Skin-related Neglected Tropical Diseases (Skin NTDs) affect about 1.8 billion people worldwide, particularly in poor and rural communities where healthcare access is limited. Many people rely on frontline health workers (FHWs) for treatment, but these workers often lack specialized training in skin diseases, making diagnosis difficult. To address this challenge, the SkincAIr project is testing whether a mobile app powered by artificial intelligence (AI) can help FHWs improve their ability to detect Skin NTDs. The study will be conducted in two arms. In the first clinical image data collection arm (36 months), dermatologists in 5 countries (Kenya, Ethiopia, Senegal, Democratic Republic of Congo and Nigeria) will collect images of skin NTD and other skin conditions that will be used for development and training of the AI model within the SkincAIr app before it is tested among FHWs. The second validation study arm will take place in 3 countries (Kenya, Ethiopia and Senegal), and will involve 50 FHWs and around 750 patients in each country over 24 months. During the first 12 months (Phase A), FHWs will diagnose patients using standard methods without the app, establishing baseline performance on key indicators including diagnostic accuracy, time to diagnosis, referral patterns, and cost implications of improved primary-level diagnosis. For the following 6 months (Phase B), FHWs will use the SkincAIr app with AI functionality activated to support diagnosis and enable real-time geolocated disease mapping and hotspot identification. In the final 6 months (Phase C), the app is withdrawn to assess whether FHWs retain their improved diagnostic skills. We will summarize the results using simple numbers and charts to show how often things happen and what the average results look like. Researchers will evaluate how well the app improves diagnosis by FHWs and whether FHWs retain their improved skills even after AI support is removed, by comparing their results with those of a skin specialist (dermatologist). Interviews and group discussions will be recorded, written down, organized into key ideas, and carefully reviewed using a computer program to understand the main themes. Study findings will be shared with National Ministries of Health, presented at local and international conferences, and reported to relevant institutional and regulatory authorities. If successful, this AI tool could boost early detection of skin diseases, enhance disease tracking, and improve healthcare in underserved areas.

Epidemiological, Clinical, Diagnostic, and Therapeutic Characteristics of Hansen's Disease in Costa Rica (2018-2025)

The goal of this observational retrospective study is to characterize the epidemiologic, clinical, diagnostic, and therapeutic features of Hansen's disease cases in Costa Rica between 2018 and 2025. The main questions it aims to answer are: What are the epidemiologic and clinical characteristics of confirmed Hansen's disease cases in Costa Rica? What diagnostic methods, treatments, complications, and outcomes are observed in routine care? All confirmed Hansen's disease cases recorded in national surveillance and with available clinical records during 2018-2025 will be included. Data will be obtained from electronic health records and Ministry of Health reports without participant contact.

Integrating Mental Health Into Neglected Tropical Disease Care in Ghana

Background Neglected Tropical Diseases (NTDs) are a group of diseases that are more common among the poorest people in the poorest countries. People affected by these conditions often experience pain, changes in their physical appearance, stigma and discrimination. As a result, they are more likely to experience mental distress including depression and anxiety. It is important that people affected by these conditions are found early, so that they can start treatment to stop the progression of the condition and to support their mental wellbeing. The World Health Organisation recently developed guidance that explains more about including mental health awareness and care as part of the management of people who have these conditions. This is called the Essential Care Package for NTDs, Stigma and Mental Health Conditions. However, so far there has been limited research about 'what works' when providing this package to people who need it. Aim of the study Through this study, we aim to understand 'How can the health system in Ghana provide the essential care package for people affected by skin NTDs for large groups of the population (at scale)?; and how to do this in a way that means everyone can access it (that is fair) and that is effective (works well)?' Methods/ Design In order to do this, we will develop a Ghanaian version of the Essential Care Package and associated resources to support its implementation. We will do this by including people affected by NTDs to help us understand the needs and priorities from their perspective. Working together with researchers, health workers and those who make decisions about health, people affected will be supported to identify their priorities and to take part in developing what will be included in this Ghanaian ECP. This will happen by using creative forms of research that encourage people to participate and through the process, with workshops to include their opinions scheduled throughout. Once this has been developed the Government will then start to introduce the Ghanaian ECP in selected study districts. At the same time, we will monitor and evaluate what is happening to understand what parts work well? who they work best for? in what settings? and for how long? We will carry out different types of research to understand who has access to this new package of services? (how fair is it?), how well it works? How the health workers and health system take up and use the new ECP? How the new ECP is rolled out and introduced as part of the health system? And whether it can be maintained and continue beyond the end of the study? Discussion Through this study, we hope that people affected by NTDs and mental health conditions will be able to access and use quality health services when they need them; that communities will have a better understanding about NTDs and mental health conditions; and that government departments will work better together to provide care for NTDs and mental health conditions together.

Novel Interventions and Diagnostic Tests for Leprosy

Contact with Mycobacterium leprae (M. leprae) infected individuals is a risk factor for development of leprosy. Thus, detection of asymtomatically M. leprae infected individuals, allowing informed decision making on who needs treatment at a preclinical stage, is vital to interrupt transmission and can help prevent leprosy. In a previous field trial the BCG vaccine was applied alone and combined with a single dose of rifampin (SDR) as prophylactic interventions in contacts of leprosy patients in Bangladesh. Concurrently, blood-derived host immune-profiles specific for M. leprae infection or leprosy disease were assessed in the same population by merging detection of innate, adaptive cellular as well as humoral immunity. This has led to the identification of selected host-immune markers, currently applied in a low complexity lateral flow assay based on up-coverting particles (UCP-LFA), providing a convenient tool to assess M. leprae infection, allowing assessment of efficacy of prophylactic interventions in a point-of-care setting. The proposed study aims to determine the effect of post-exposure prophylaxis by SDR on M. leprae infection rate using UCP-LFA before and after prophylaxis.

Efficacy and Tolerability of Adjunct Metformin for Multibacillary Leprosy

This trial aims to evaluate the efficacy, tolerability and safety of adjunct metformin added to standard-of-care multi-drug therapy (MDT) in patients with multibacillary leprosy, and explore its effects on immunological endpoints. A double-blind, placebo controlled proof-of-concept trial will be performed in which patients with newly diagnosed multibacillary leprosy will be randomized (1:1) to metformin 1000mg OD versus placebo for 24 weeks in addition to MDT during 48 weeks. The main research question is whether adjunctive metformin, combined with MDT, will improve the clinical outcomes of patients with multibacillary leprosy by mitigating leprosy reactions, thereby reducing nerve damage and corticosteroid use and its associated morbidity. The second aim is to explore whether adjunct metformin, added to MDT, has an acceptable tolerability and safety in patients with multibacillary leprosy.

Leprosy Active Searching Trial in Brazil

The goal of this clinical trial is to assess whether a multifactorial active case-finding strategy improves the detection of leprosy cases in Brazil compared to usual screening practices. The main questions it aims to answer are: \- Does the intervention increase the number of new leprosy cases detected compared to standard care? Participants will: * Receive community awareness about leprosy. * Be screened using the Leprosy Suspicion Questionnaire at priority areas identified by georeference tools. * Undergo clinical evaluation by a trained medical team. * If leprosy is diagnosed, affected patients will collect complementary laboratory exams Healthcare professionals from primary care units will receive training in leprosy, while researchers will monitor changes in leprosy incidence over a 12-month period using data from Brazil's national notification system. The study will provide insights into underdiagnosis and the clinical profiles of patients who have been diagnosed.

Rab 32 Gene Polymorphisms as a Prognostic Factor in Leprosy Patients

Mycobacterium leprae is a slow-growing bacillus that causes leprosy. the infection may take two to ten years to incubate. While the exact mechanism of infection transmission is unknown, direct bacillus absorption through the nasal or respiratory mucosa and aerosolized nasal secretions are the most common theories. The bacteria is subsequently transported by the bloodstream to the peripheral nerves, where it can result in tissue damage from painless burns and ulcers as well as irreparable nerve damage that results in a loss of protective feeling.

TGF β 1 Expression Related Gene Polymorphism

Leprosy is one of the oldest human infectious diseases. It is a chronic infectious contagious, granulomatous disease caused by intracellular bacillus. Mycobacterium leprae, this chronic granulomatous disease presents symptoms that mainly affected the skin, the nervous system and the reticuloendothelial system, also other systems can be affected, such as the upper respiratory tract, bones and joints, eyes and adrenal glands. TGF- β is a pleiotropic cytokine that employs several functions on different types of cells. The effect of other cytokines may finally modulate the cellular response in the presence of TGF- β, causing a different effect depending on the activation state of the cell involved. In addition, TGF- β promotes the healing of inflamed tissue through the stimulation and regulation of extracellular matrix by fibroblasts, in addition to inducing the proliferation of endothelial cells required for angiogenesis. Thus, TGF- β is able to regulate the expression of other growth factors, increasing their level of activity.

Trial LEP-F1 + GLA-SE in Healthy Adult in Areas Endemic for Leprosy

This is a phase 1b, double-blind, randomized, placebo-controlled clinical trial to evaluate the safety, tolerability, and immunogenicity of LEP-F1 + GLA-SE compared to placebo administered as three intramuscular (IM) injections in adult participants aged 18 to 55.

Bedaquiline Enhanced Post ExpOsure Prophylaxis for Leprosy

There will be two study arms. Arm 1 will be the intervention arm in which there will be provided BE-PEP to all persons residing within 100 meters of an index case, to be repeated after four weeks for household contacts. Arm 2 will be the comparator arm in which the WHO recommended standard PEP will be provided, i.e. 10 mg/kg of rifampicin in a single dose. In both arms the investigators will target anyone living within 100 meters of an index case or the entire village if more than 50% are eligible. Provision of BE-PEP will start in 2023 and follow-up will continue until 2026. The main study outcome will be the comparison of leprosy risk in individuals that received BE-PEOPLE standard WHO SDR-PEP versus individuals that received BE-PEP. In addition the investigators will compare the overall leprosy incidence over the follow-up period between the two study arms.