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Genome comparison of progressively drug resistant Plasmodium falciparum lines derived from drug sensitive clone
Toteja, Ravi; Nair, Lathika; Bhasin, Vk.
  • Toteja, Ravi; University of Delhi. Department of Zoology. Delhi. IN
  • Nair, Lathika; University of Delhi. Department of Zoology. Delhi. IN
  • Bhasin, Vk; University of Delhi. Department of Zoology. Delhi. IN
Mem. Inst. Oswaldo Cruz ; 96(3): 427-433, Apr. 2001. ilus, tab
Artigo em Inglês | LILACS | ID: lil-282857
ABSTRACT
Chloroquine has been the mainstay of malaria chemotherapy for the past five decades, but resistance is now widespread. Pyrimethamine or proguanil form an important component of some alternate drug combinations being used for treatment of uncomplicated Plasmodium falciparum infections in areas of chloroquine resistance. Both pyrimethamine and proguanil are dihydrofolate reductase (DHFR) inhibitors, the proguanil acting primarily through its major metabolite cycloguanil. Resistance to these drugs arises due to specific point mutations in the dhfr gene. Cross resistance between cycloguanil and pyrimethamine is not absolute. It is, therefore, important to investigate mutation rates in P. falciparum for pyrimethamine and proguanil so that DHFR inhibitor with less mutation rate is favored in drug combinations. Hence, we have compared mutation rates in P. falciparum genome for pyrimethamine and cycloguanil. Using erythrocytic stages of P. falciparum cultures, progressively drug resistant lines were selected in vitro and comparing their RFLP profile with a repeat sequence. Our finding suggests that pyrimethamine has higher mutation rate compared to cycloguanil. It enhances the degree of genomic polymorphism leading to diversity of natural parasite population which in turn is predisposes the parasites for faster selection of resistance to some other antimalarial drugs
Assuntos
Texto completo: DisponíveL Índice: LILACS (Américas) Assunto principal: Plasmodium falciparum / Antimaláricos Tipo de estudo: Estudo diagnóstico Limite: Animais / Humanos Idioma: Inglês Revista: Mem. Inst. Oswaldo Cruz Assunto da revista: Medicina Tropical / Parasitologia Ano de publicação: 2001 Tipo de documento: Artigo País de afiliação: Índia Instituição/País de afiliação: University of Delhi/IN

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Texto completo: DisponíveL Índice: LILACS (Américas) Assunto principal: Plasmodium falciparum / Antimaláricos Tipo de estudo: Estudo diagnóstico Limite: Animais / Humanos Idioma: Inglês Revista: Mem. Inst. Oswaldo Cruz Assunto da revista: Medicina Tropical / Parasitologia Ano de publicação: 2001 Tipo de documento: Artigo País de afiliação: Índia Instituição/País de afiliação: University of Delhi/IN