Pediatric Leishmaniasis Medication

  • Author: Conjivaram Vidyashankar, MD, MRCP; Chief Editor: Russell W Steele, MD   more...
 
Updated: Aug 10, 2011
 

Medication Summary

Sodium stibogluconate is the drug of choice in most areas. However, resistance is rising.

Supportive treatment includes rest, high-calorie diet, blood transfusions, and treatment of secondary infections.

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Pentavalent Antimony Compounds

Class Summary

These compounds are the drugs of choice in patients with visceral leishmaniasis. Sodium stibogluconate is a compound available in English-speaking countries, and meglumine antimonate is a compound available in Latin American countries.

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Sodium stibogluconate (Pentostam)

 

DOC to treat leishmaniasis in the United States; also known as sodium antimony gluconate. Acts by interfering with the metabolism of the parasite.

Aqueous preparation is available in a concentration of 100 mg/mL only from the CDC. Patients with long-standing disease may require long-term therapy. Can be administered at recommended dose for 30 d without toxicity.

Pharmacokinetic parameters are similar with IV/IM administration. Primary unresponsiveness ranges from 2-8%. Relapse rate is usually < 10% but has been reported to be as high as 30% in Kenya. Increasing incidence of resistance is reported in India.

Aminosidine (Gabbromicina)

 

PO product Humatin (called paromomycin [Humantin] in United States) available in United States as an orphan drug. IV and topical products are not available in the United States. Amebicidal and antibacterial aminoglycoside obtained from a strain of Streptomyces rimosus, active in intestinal amebiasis.

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Antiprotozoal Agent

Class Summary

Parasite biochemical pathways are different from the human host; thus, drug treatment is directed to the life cycle and may affect the parasite, egg, or larvae.

Miltefosine (Miltex)

 

First-line, PO antileishmanial agent approved in India. A synthetic ether phospholipid analog similar to natural phospholipids present in cell membranes. Elicits antineoplastic, immunomodulatory, antiviral, and antiprotozoal activity. Mechanism unknown, but thought to inhibit enzyme systems (eg, protein kinase-C) in cell membranes and phosphatidylcholine biosynthesis. A short-course regimen consisting of a single dose of liposomal amphotericin followed by 7-14 d of miltefosine has resulted in cure rates of over 90% in north India.

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Systemic Antifungal Agents

Class Summary

These agents are used in resistant leishmaniasis in combination with other agents. Mechanisms of action may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.

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Amphotericin B, liposomal (AmBisome)

 

Lipid complex with amphotericin that is more active than amphotericin B. Produced by a strain of Streptomyces nodosus. Can be fungistatic or fungicidal. Binds to sterols (eg, ergosterol) in the fungal cell membrane, causing intracellular components to leak with subsequent fungal cell death.

The 3 preparations formulated include amphotericin B lipid complex (Abelcet), liposomal amphotericin B (AmBisome), and amphotericin B colloidal dispersion (Amphotec).

Cure rates of >90% have been observed in various studies. A short-course regimen consisting of a single dose of liposomal amphotericin followed by 7-14 d of miltefosine has resulted in cure rates of >90% in north India. High cost is a disadvantage to its use in areas where visceral leishmaniasis is prevalent.

Available as 100 mg/20 mL preparation.

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Ketoconazole (Nizoral)

 

Imidazole broad-spectrum antifungal agent; inhibits synthesis of ergosterol, which causes cellular components to leak, resulting in fungal cell death.

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Itraconazole (Sporanox)

 

Synthetic triazole antifungal agent that slows fungal cell growth by inhibiting CYP-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes.

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Xanthine Oxidase Inhibitor

Class Summary

These agents may be added to first-line drugs.

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Allopurinol (Zyloprim)

 

Inhibits xanthine oxidase, the enzyme that synthesizes uric acid from hypoxanthine. Reduces the synthesis of uric acid without disrupting the biosynthesis of vital purines. Not effective as monotherapy for leishmaniasis.

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Antibiotic Agents

Class Summary

Available preparations include pentamidine isethionate (Pentam) and pentamidine dimethanesulfonate (Lomidine). Pentamidine dimethane sulphonate administered in the same dose schedule is more effective than pentamidine isethionate.

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Pentamidine (Lomidine)

 

Inhibits growth of protozoa by blocking oxidative phosphorylation and inhibiting incorporation of nucleic acids into RNA and DNA, causing inhibition of protein and phospholipid synthesis.

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Immunomodulatory Agents

Class Summary

Interferons are naturally occurring cytokines that possess various biological functions, which include immunosuppressive action. They are produced by cells in response to virus, double-stranded RNA, antigen, or mitogen, and are classified in relation to biochemical properties and cell of origin. They are commercially produced with recombinant DNA technology.

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Interferon gamma-1b (Actimmune)

 

Naturally occurring cytokine that possesses antiviral, immunomodulatory, and antiproliferative activity. Commercially available as a protein product manufactured by recombinant DNA technology.

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Contributor Information and Disclosures
Author

Conjivaram Vidyashankar, MD, MRCP  Specialty Doctor Paediatrics, Stafford District General Hospital, Stafford, UK

Conjivaram Vidyashankar, MD, MRCP is a member of the following medical societies: European Society for Paediatric Infectious Diseases, Indian Academy of Pediatrics, International AIDS Society, and Royal College of Paediatrics and Child Health

Disclosure: Nothing to disclose.

Coauthor(s)

Ruchir Agrawal, MD  Chief, Allergy and Immunology, Aurora Sheboygan Clinic

Ruchir Agrawal, MD, is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American College of Allergy, Asthma and Immunology, and American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Gary J Noel, MD  Professor, Department of Pediatrics, Weill Cornell Medical College; Attending Pediatrician, New York-Presbyterian Hospital

Gary J Noel, MD is a member of the following medical societies: Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Martin Weisse, MD  Program Director, Associate Professor, Department of Pediatrics, West Virginia University

Martin Weisse, MD is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Robert W Tolan Jr, MD  Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine

Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility

Disclosure: GlaxoSmithKline Honoraria Speaking and teaching; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; Sanofi Pasteur Honoraria Speaking and teaching; Baxter Healthcare Honoraria Speaking and teaching; Novartis Honoraria Speaking and teaching

Chief Editor

Russell W Steele, MD  Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association

Disclosure: Nothing to disclose.

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Distribution map of visceral leishmaniasis.
Distribution map of cutaneous leishmaniasis.
Distribution map of human immunodeficiency virus (HIV) and leishmaniasis co-infection.
The predominant mode of transmission is the sandfly's bite.
Leishmania donovani is one of the main Leishmania species that infects humans.
 
 
 
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