View clinical trials related to Leishmaniasis, Visceral.
Filter by:Burden: Post-Kala-Azar Dermal Leishmaniasis (PKDL) commonly follows visceral leishmaniasis (VL) caused by Leishmania donovani. It is characterized by skin lesions in which parasites can be identified, in a patient who is otherwise fully recovered from VL or exposed to L. donovani (LD) infection. It occurs in the Indian subcontinent (mainly India and Bangladesh) as well as in Africa (mainly Sudan). It is now established that PKDL patients play an important role in transmission of LD parasite where chronic PKDL patients have been implicated in major VL outbreaks in the past. Though VL cases are in decline due to extensive programmes conducted by NKEP, PKDL cases are in the rise and VL:PKDL ratio has risen from 1:0.47 to 1:1.21 from 2016 to 2020. In this current situation, elimination of PKDL cases is of crucial importance in the current VL elimination efforts in Bangladesh as well as in the Indian subcontinent. Knowledge gap: Currently there are no satisfactory treatments for any forms of PKDL. Both miltefosine and Ambisome® as monotherapy have shown to be effective. However, with the current recommended scheme there are some drawbacks such as the length of the treatment with miltefosine alone (8-12 weeks), toxicity related to it; a high dose Ambisome® (total dose of 20 mg/kg) given frequently in 4 divided dosage often causes adverse events (e.g. pancytopania, hypokalemia, increased creatinine level etc.). There is also the potential risk for development of resistance with miltefosine as monotherapy. Ivermectin has been proven to have a significant leishmanicidal effect by several experimental studies at higher doses without significant toxicity and may offer shorter duration of treatment thus preventing prolonged hospitalization. Another possible advantage is reduction of cost. These principles can be applied to PKDL, where the need for an ambulatory treatment with a highly safe, efficacious and user friendly regimen is even more pressing as the patients feel otherwise healthy, except for the rashes. Relevance: This study aims primarily to improve current treatment options. In addition, this will be the first human study ever in PKDL in relation to Ivermectin, in which outcome will be described in clinical, parasitological and immunological terms. Ultimately this study findings will help National Kala-Azar Elimination Program (NKAEP) to adopt specific strategies for elimination of PKDL cases. Hypothesis (if any): Oral ivermectin in multiple doses is safe and more effective than Miltefosine for the treatment of PKDL cases. Objectives: To measure the safety and efficacy of Ivermectin monotherapy regimen (60 mg oral on five consecutive days, for three consecutive months) in comparison to oral Miltefosine allometric dose for twelve weeks, for treating PKDL patients in Bangladesh. Methods: This will be a comparative, open label, non-blinded, individually randomized, proof-of-concept Clinical Trial to assess the safety and efficacy of oral Ivermectin monotherapy (5 x 12 mg daily at a total dose of 60 mg per month for three consecutive months, 180 mg in total) and Miltefosine monotherapy (50 mg twice daily for 12 weeks) in treating PKDL patients in Bangladesh. All participants will be recruited at SKKRC, Mymensingh with due consent. All patients will be followed up for 12 months. Cure assessment will be performed. Outcome measures/variables: Safety and efficacy of Ivermectin for PKDL treatment will be determined.
Visceral leishmaniasis (VL) or kala azar is a neglected tropical disease(NTD) caused by protozoan parasites of the Leishmania donovani complex that are transmitted by phlebotomine sand flies. An estimated 50,000 - 90,000 new cases occur worldwide annually. It is characterized by fever, weight loss, enlargement of the spleen and liver, and anaemia, and it can be fatal in more than 95% of cases without treatment. The Horn of Africa accounts for the largest number of VL cases worldwide, and communities living in remote, resource-limited settings are at greatest risk of infection. Therefore, early and accurate diagnosis of VL in health facilities is essential. VL is fatal if it is not adequately treated. The drugs currently used to treat VL can have severe side effects and the clinical presentation of VL is not sufficiently specific to guide treatment. Highly accurate (both sensitive and specific), cheap and simple rapid diagnostic tests (RDTs) are therefore crucial for case-management of VL. Early case detection followed by adequate treatment is also central to control of VL. In Kenya, Visceral leishmaniasis is diagnosed by the rK39 RDT based on detection of host antibody to a 39-aminoacid-repeat recombinant leishmanial antigen in clinically suspected cases. Because this test has a suboptimal sensitivity of around 85%, other additional diagnostic tests are often necessary. These include the direct agglutination test (DAT) based on agglutination of whole parasite antigen by parasite specific host antibodies and microscopy detection of amastigotes in stained smears from lymph node punctures, bone marrow or spleen aspirates currently the gold standard for confirmatory diagnosis. While the use of rK39 RDT and DAT has been on the increase, the tests cannot distinguish active from past infections as they are based on detection of antileishmania antibodies which are present in both active and past infections. Furthermore, DAT requires some laboratory skills and overnight incubations before obtaining the results and the rK39 has low sensitivity when used in Eastern Africa. There have therefore been efforts to develop an antigen detection based test that is based on minimally invasive specimen collection such as blood or urine. To this end, a collaboration between KEMRI, DNDi, FIND and the University of York under the Next generation diagnostics and oral treatment for visceral leishmaniasis in Eastern Africa: transforming patient care through innovation (VL-INNO) EDCTP project, aims to develop an antigen based diagnostic test based on parasite biomarkers in urine and blood from VL patients. In this project, a proteomics approach will be used to identify candidate Leishmania antigens that are found in the blood and urine of confirmed visceral leishmaniasis. The University of York will undertake proteomics analyses of the specimens using highly sensitive Liquid Chromatograph Triple Quadrupole Mass Spectrometer (LCMS/MS) to explore antigen diversity in defined archived clinical samples (blood, urine) from VL patients before and after treatment. Based on yield, stability and immunogenicity of the antigens, monoclonal antibodies (mAb) will be production for subsequent development of a lateral flow rapid diagnostic test(RDT) prototype that can detect leishmania antigens in blood and/or urine of VL patients. With these activities initiated using samples previously collected from VL patients in Kenya, this current protocol seeks to collect samples (blood and urine) from two VL treatment centres namely Chemolingot Sub-county hospital in Baringo County and Kacheliba Sub-county, West Pokot, to be used in the evaluation of the RDT prototype. We will analyze samples from VL patients collected before and at the end of treatment, to determine the sensitivity of the test and how parasite antigen abundance in urine and blood changes as a consequence of clinical cure. Samples from healthy endemic controls will be used to determine the specificity of the test.
This is a randomized, open-label, phase II, single-centre study, with one LXE408 regimen and one calibrator arm with the standard of care SSG combined with PM, to be conducted in male and female adult (≥18 years and <45 years) patients with confirmed primary visceral leishmaniasis in Ethiopia.
This prospective cohort study has the aim to develop a prognostic tool to predict relapse in patients suffering from visceral leishmaniasis (VL) from VL endemic regions in Ethiopia. Therefore, comprehensive clinical and laboratory characterization of all confirmed VL patients before and during treatment will be performed in order to identify the factors that determine prognosis of the patients. This approach would result in more efficient patient care and would reduce the case fatality and morbidity, and improve follow-up and care for those at risk of VL relapse.
This is a phase II, multicentre, randomized, two-arm blinded study with an open label calibrator arm in adults and adolescents (≥12 years) with confirmed primary VL.
This study aims to describe the burden of Post-Kala-Azar Dermal Leishmaniasis and visceral leishmaniasis relapse in a cohort of patients discharged after successful treatment of primary visceral leishmaniasis.
Left untreated, visceral leishmaniasis (VL) is fatal. The highest burden of VL worldwide is in eastern Africa where field-adapted diagnostic and test-of-cure tools and treatment are lacking. The current laboratory tool to help assessing cure, treatment failure and relapse is microscopy, based on invasive sampling (e.g. splenic or bone marrow aspirate). Non-invasive, more sensitive tools will enable these assessments with minimum risk and discomfort to patients. This study aims to evaluate immunological and molecular tests to predict cure and relapse, and to replace with these the current invasive methods. The study will be conducted at the Leishmaniasis Research and Treatment Centre (LRTC), Gondar University Hospital, Ethiopia It will be a non-intervention study, the tools under evaluation will be considered as index tests; their results will not influence patient management during the duration of the study. Patient management will follow the national guidelines for VL diagnosis and management in Ethiopia.
Visceral leishmaniasis (VL) is a fatal disease caused by Leishmania parasites and transmitted by female phlebotomine sandflies. The disease is a serious public health problem in eastern Africa; including Kenya where an estimated 4000 cases occur annually and 5 million people are at risk of infection. Accurate diagnosis of VL is critical for appropriate treatment. Currently, VL diagnosis in Kenya is based on testing suspected patients with the IT-Leish rK39 rapid diagnostic test (RDT) followed by other tests such as the Direct Agglutination Tests (DAT) and microscopy of tissue aspirates (splenic, bone marrow, lymph node) on rK39-negative patients. However, these diagnostic tools present several challenges including; the need for expertise, equipment and low diagnostic sensitivity of (85%) for DAT and rK39. Alternative VL diagnostic tools that are readily available, easy to use with increased sensitivity are needed to improve VL surveillance and control in Kenya. In the present study, we will assess rK28 as a diagnostic tool including performance with increased sensitivity when used together with IT-Leish rK39 and its potential for inclusion in VL diagnosis algorithms and evaluate Kala-azar Detect rK39 for potential use in Kenya. Suspected patients presenting at VL testing facilities in Marsabit, Turkana and Wajir Counties will be recruited prospectively and tested using IT-Leish rK39 followed by DAT for case confirmation according to the national guidelines. Alongside the case confirmation, samples from participants will also be tested using the rK28 and Kala-azar Detect rK39 in whole blood and serum. The collected data will be analyzed and compared separately between the RDTs as well as in combination, and the performance of the algorithms determined retrospectively. This design will enable the assessment of the sensitivity of combining rK28 and rK39 (Kala-azar Detect) compared to rK39 (IT-Leish/Kala-azar Detect) alone. Microscopy will be used as confirmatory test. We will also assess the feasibility, usefulness, and cost-effectiveness of rK28 in the VL diagnostic algorithm, through sensitivity analyses. The improved understanding of rK28 as a VL diagnostic tool and its potential for inclusion in the VL diagnosis algorithm could enable faster and more effective management of cases and accelerate elimination of VL.
ImmStat@Cure is a multicentre observational study designed to assess the immune status of patients before and after treatment for visceral leishmaniasis. Forty patients and 30 controls will be recruited per site. The follow-up period is 6 months from the end of treatment.
The actual format of the anticipated LEISH3 trial is under review.