Drug unresponsiveness & combination therapy for kala-azar.
Artigo
em Inglês
| IMSEAR
| ID: sea-23553
ABSTRACT
Pentavalent antimonials (SbV) have been successfully used for treatment of kala-azar since last six decades. Since 1970s its conventional dosages have failed to achieve with 60 per cent unresponsiveness reported with WHO regimen in Bihar (India). Pentamidine initially used as a second line of drug, acquired resistance (25%) even with prolonged dosage. Newer oral drug miltefosine is a potent antileishmanial drug with longer half-life, a property likely to acquire resistance. Paromomycin has undergone extensive clinical trials in Indian kala-azar patients. Being an aminoglycoside, acquired resistance is likely to occur when used as a monotherapy. To encounter the problem of treatment failure in kala-azar and to reduce length of therapy, combination of at least two effective antileishmanial agents is a desirable option. In India sodium stibogluconate (SSG) in standard dose has been combined with other antileishmanial agents including paromomycin without encouraging result. Infection with Leishmania donovani depresses cell-mediated immunity. Immunological balance is tilted in favour of Th2 suppressive cytokines over Th1 producing protective cytokines. Interferon gamma (IFN-gamma) has been used in combination with SbV in Indian kala-azar patients with unexpectedly discouraging results. Combination of two most potent leishmanicidal drugs amphotericin B and miltefosine which are not dependent on host immune system, may shorten the course of therapy besides encountering unresponsiveness. A combination therapy should be preferred when treating kala-azar associated with HIV/AIDS. Immunotherapy with exogenous Th1 stimulating cytokines or use of antileishmanial vaccine in combination with a potent chemotherapeutic agent is a future option.
Texto completo:
DisponíveL
Índice:
IMSEAR (Sudeste Asiático)
Assunto principal:
Fosforilcolina
/
Humanos
/
Resistência a Medicamentos
/
Anfotericina B
/
Índia
/
Leishmania
/
Leishmaniose Visceral
/
Animais
/
Antiprotozoários
País/Região como assunto:
Ásia
Idioma:
Inglês
Ano de publicação:
2006
Tipo de documento:
Artigo
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