Abstract
Human African trypanosomiasis or sleeping sickness is resurgent [1,2]. The disease is caused by subspecies of the parasitic haemoflagellate, Trypanosoma brucei. Infection starts with the bite of an infected tsetse fly (Glossina spp.). Parasites move from the site of infection to the draining lymphatic vessels and blood stream. The parasites proliferate within the bloodstream and later invade other tissues including the central nervous system. Once they have established themselves within the CNS, a progressive breakdown of neurological function accompanies the disease. Coma precedes death during this late phase. Two forms of the disease are recognised, one caused by Trypanosoma brucei rhodesiense, endemic in Eastern and Southern Africa, in which parasites rapidly invade the CNS causing death within weeks if untreated. T. b. gambiense, originally described in West Africa, but also widespread in Central Africa, proliferates more slowly and can take several years before establishing a CNS-involved infection. Many countries are in the midst of epidemics caused by gambiense-type parasites. Four drugs have been licensed to treat the disease [3] two of them, pentamidine and suramin, are used prior to CNS involvement. The arsenic-based drug, melarsoprol is used once parasites are established in the CNS. The fourth, eflornithine, is effective against late stage disease caused by T. b. gambiense, but is ineffective against T. b. rhodesiense. Another drug, nifurtimox is licensed for South American trypanosomiasis but also been used in trials against melarsoprol-refractory late sage disease. This review focuses on what is known about modes of action of current drugs and discusses targets for future drug development.
Keywords: Trypanosomiasis, Trypanosoma, Trypanosoma brucei rhodesiense, Suramin, Pentamidine, Melarsoprol, Eflornithine, Nifurtimox
Current Pharmaceutical Design
Title: Chemotherapy of Human African Trypanosomiasis
Volume: 8 Issue: 4
Author(s): Richard J.S. Burchmore, Patrick O.J. Ogbunude, Bertin Enanga and Michael P. Barrett
Affiliation:
Keywords: Trypanosomiasis, Trypanosoma, Trypanosoma brucei rhodesiense, Suramin, Pentamidine, Melarsoprol, Eflornithine, Nifurtimox
Abstract: Human African trypanosomiasis or sleeping sickness is resurgent [1,2]. The disease is caused by subspecies of the parasitic haemoflagellate, Trypanosoma brucei. Infection starts with the bite of an infected tsetse fly (Glossina spp.). Parasites move from the site of infection to the draining lymphatic vessels and blood stream. The parasites proliferate within the bloodstream and later invade other tissues including the central nervous system. Once they have established themselves within the CNS, a progressive breakdown of neurological function accompanies the disease. Coma precedes death during this late phase. Two forms of the disease are recognised, one caused by Trypanosoma brucei rhodesiense, endemic in Eastern and Southern Africa, in which parasites rapidly invade the CNS causing death within weeks if untreated. T. b. gambiense, originally described in West Africa, but also widespread in Central Africa, proliferates more slowly and can take several years before establishing a CNS-involved infection. Many countries are in the midst of epidemics caused by gambiense-type parasites. Four drugs have been licensed to treat the disease [3] two of them, pentamidine and suramin, are used prior to CNS involvement. The arsenic-based drug, melarsoprol is used once parasites are established in the CNS. The fourth, eflornithine, is effective against late stage disease caused by T. b. gambiense, but is ineffective against T. b. rhodesiense. Another drug, nifurtimox is licensed for South American trypanosomiasis but also been used in trials against melarsoprol-refractory late sage disease. This review focuses on what is known about modes of action of current drugs and discusses targets for future drug development.
Export Options
About this article
Cite this article as:
Burchmore J.S. Richard, Ogbunude O.J. Patrick, Enanga Bertin and Barrett P. Michael, Chemotherapy of Human African Trypanosomiasis, Current Pharmaceutical Design 2002; 8 (4) . https://dx.doi.org/10.2174/1381612023396159
DOI https://dx.doi.org/10.2174/1381612023396159 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Focus on Immunology of Trichinellosis
Medicinal Chemistry Reviews - Online (Discontinued) Bortezomib – First Therapeutic Proteasome Inhibitor for Cancer Therapy: A Review of Patent Literature
Recent Patents on Anti-Cancer Drug Discovery Innovative Concepts of Cell Therapy: Pluripotent and Multipotent Stem Cells and New Bio-Material Solution in Research and Clinical Application
Recent Patents on Regenerative Medicine Designing Peptide Mimetics for the Treatment of Multiple Sclerosis
Mini-Reviews in Medicinal Chemistry Seq and You Will Find
Current Gene Therapy Neuronal-glial Interactions Define the Role of Nitric Oxide in Neural Functional Processes
Current Neuropharmacology Microglial Activation as a Compelling Target for Treating Acute Traumatic Brain Injury
Current Medicinal Chemistry Survey of Latin American Neuroimmunologists on the Treatment of Multiple Sclerosis with Monoclonal Antibodies
Current Drug Safety Editorial (Thematic Issue: Ferid Murad, at 80: A Legacy of Science, Medicine, and Mentorship)
Current Medicinal Chemistry Diagnosis and Treatment of Paraneoplastic Neurological Syndromes
Current Clinical Pharmacology Orally Administrated Small Molecule Drugs with Intestine Targeted Profile: Recent Development and Prospects
Current Medicinal Chemistry Patent Selections
Recent Patents on CNS Drug Discovery (Discontinued) New Organ-Specific Drug Strategies Interfering in Signaling Pathways: Kinase Inhibitors and Other New Developmental Drugs in HCC
Current Signal Transduction Therapy Editorial (Thematic Issue: Crosstalk Between the Nervous and the Immune Systems in Health and Sickness)
Current Pharmaceutical Design Emerging Targets for the Pharmacological Treatment of Depression: Focus on Melatonergic System
Current Medicinal Chemistry Potential Pathways for CNS Drug Delivery Across the Blood-Cerebrospinal Fluid Barrier
Current Pharmaceutical Design Catalpol: A Potential Therapeutic for Neurodegenerative Diseases
Current Medicinal Chemistry Applications of Integrated Data Mining Methods to Exploring Natural Product Space for Acetylcholinesterase Inhibitors
Combinatorial Chemistry & High Throughput Screening Hypersensitivity to Antineoplastic Agents
Current Pharmaceutical Design Fyn Kinase in Brain Diseases and Cancer: The Search for Inhibitors
Current Medicinal Chemistry