Evidence for different mechanisms of chloroquine resistance in 2 Plasmodium species that cause human malaria
| Autor: | William E. Collins, Thomas F. McCutchan, David A. Fidock, Xin-zhuan Su, Dharmendar Rathore, J. Kevin Baird, David J. Fryauff, Takashi Nomura, Thomas E. Wellems, Jane M. Carlton, Hernando A. del Portillo, John C. Wootton |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Plasmodium
Molecular Sequence Data Plasmodium vivax Drug Resistance Disease Biology Apicomplexa Parasitic Sensitivity Tests Chloroquine parasitic diseases medicine Animals Humans Immunology and Allergy Dictyostelium Amino Acid Sequence Codon Genetics fungi Plasmodium falciparum medicine.disease biology.organism_classification Virology Infectious Diseases Mutation Protozoa Sequence Alignment Malaria Molecular Chaperones medicine.drug |
| Popis: | Chloroquine (CQ)–resistant Plasmodium vivax malaria was first reported 12 years ago, nearly 30 years after the recognition of CQ-resistant P. falciparum. Loss of CQ efficacy now poses a severe problem for the prevention and treatment of both diseases. Mutations in a digestive vacuole protein encoded by a 13-exon gene, pfcrt, were shown recently to have a central role in the CQ resistance (CQR) of P. falciparum. Whether mutations in pfcrt orthologues of other Plasmodium species are involved in CQR remains an open question. This report describes pfcrt homologues from P. vivax, P. knowlesi, P. berghei, and Dictyostelium discoideum. Synteny between the P. falciparum and P. vivax genes is demonstrated. However, a survey of patient isolates and monkey-adapted lines has shown no association between in vivo CQR and codon mutations in the P. vivax gene. This is evidence that the molecular events underlying P. vivax CQR differ from those in P. falciparum. In malaria campaigns, the morbidity and mortality of Plasmodium falciparum malaria in Africa is often emphasized, whereas the global impact of the less deadly malaria caused by P. vivax is overshadowed. Although P. vivax malaria rarely is fatal, it is, nevertheless, a debilitating disease with tremendous impact on the quality of life and economic productivity. Estimates of the annual number of P. vivax cases range from 75 to 90 million, with most occurring outside Africa. Chloroquine (CQ) has been the drug of choice for eliminating P. vivax blood stages, but resistance has been an increasing problem since it was first re |
| Databáze: | OpenAIRE |
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