Leishmaniasis medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Common drugs to treat leishmaniasis include meglumine antimoniate, sodium stibogluconate, amphotericin and miltefosine.
Medical Therapy
Acute Pharmacotherapy
There are two common therapies containing antimony (known as pentavalent antimonials), meglumine antimoniate (Glucantim®) and sodium stibogluconate (Pentostam®). It is not completely understood how these drugs act against the parasite; they may disrupt its energy production or trypanothione metabolism. Unfortunately, in many parts of the world, the parasite has become resistant to antimony and for visceral or mucocutaneous leishmaniasis,[1] but the level of resistance varies according to species.[2] Amphotericin is now the treatment of choice[3]; failure of AmBisome® to treat visceral leishmaniasis (Leishmania donovani) has been reported in Sudan,[4] but this failure may be related to host factors such as co-infection with HIV or tuberculosis rather than parasite resistance.
Miltefosine (Impavido®), is a new drug for visceral and cutaneous leishmaniasis. The cure rate of miltefosine in phase III clinical trials is 95%; Studies in Ethiopia show that is also effective in Africa. In HIV immunosuppressed people who are coinfected with leishmaniasis it has shown that even in resistant cases 2/3 of the people responded to this new treatment. Clinical trials in Colombia showed a high efficacy for cutaneous leishmaniasis. In mucocutaneous cases caused by L.brasiliensis it has shown to be more effective than other drugs. Miltefosine received approval by the Indian regulatory authorities in 2002 and in Germany in 2004. In 2005 it received the first approval for cutaneous leishmaniasis in Colombia. Miltefosine is also currently being investigated as treatment for mucocutaneous leishmaniasis caused by Leishmania braziliensis in Colombia,[1] and preliminary results are very promising. It is now registered in many countries and is the first orally administered breakthrough therapy for visceral and cutaneous leishmaniasis.[5](More, et al, 2003). In October 2006 it received orphan drug status from the US Food and Drug administration. The drug is generally better tolerated than other drugs. Main side effects are gastrointetinal disturbance in the 1-2 days of treatment which does not affect the efficacy. Because it is available as an oral formulation, the expense and inconvenience of hospitalisation is avoided, which makes it an attractive alternative.
The Institute for OneWorld Health has developed paromomycin, results with which led to its approval as an orphan drug. The Drugs for Neglected Diseases Initiative is also actively facilitating the search for novel therapeutics.
Drug-resistant leishmaniasis may respond to immunotherapy (inoculation with parasite antigens plus an adjuvant) which aims to stimulate the body's own immune system to kill the parasite.[6]
Several potential vaccines are being developed, under pressure from the World Health Organization, but as of 2006 none is available. The team at the Laboratory for Organic Chemistry at the Swiss Federal Institute of Technology (ETH) in Zürich are trying to design a carbohydrate-based vaccine [2]. The genome of the parasite Leishmania major has been sequenced,[7] possibly allowing for identification of proteins that are used by the pathogen but not by humans; these proteins are potential targets for drug treatments.
References
- ↑ 1.0 1.1 Soto J, Toledo JT. "Oral miltefosine to treat new world cutaneous leishmaniasis". Lancet Infect Dis. 7 (1): 7.
- ↑ Arevalo J, Ramirez L, Adaui V; et al. (2007). "Influence of Leishmania (Viannia) species on the response to antimonial treatment in patients with American tegumentary leishmaniasis". J Infect Dis. 195: 1846&ndash, 51. doi:10.1086/518041.
- ↑ Sundar S, Chakravarty J, Rai VK; et al. (2007). "Amphotericin B Treatment for Indian Visceral Leishmaniasis: Response to 15 Daily versus Alternate-Day Infusions". Clin Infect Dis. 45: 556&ndash, 561.
- ↑ Mueller M, Ritmeijer K, Balasegaram M, Koummuki Y, Santana MR, Davidson R. (2007). "Unresponsiveness to AmBisome® in some Sudanese patients with kala-azar". Trans R Soc Trop Med Hyg. 101 (1): 19&ndash, 24. doi:10.1016/j.trstmh.2006.02.005.
- ↑ Jha TK, Sundar S, Thakur CP; et al. (1999). "Miltefosine, an oral agent, for the treatment of Indian visceral leishmaniasis". New Engl J Med. 341: 1795&ndash, 800.
- ↑ Badaro R, Lobo I, Munõs A; et al. (2006). "Immunotherapy for drug-refractory mucosal leishmaniasis". J Infect Dis. 194: 1151&ndash, 59.
- ↑ Ivens AC; et al. (2005). "The genome of the kinetoplastid parasite, Leishmania major". Science. 309 (5733): 436&ndash, 42. PMID 16020728.