Alexis Nzila

Summary

Affiliation: Kenya Medical Research Institute
Country: Kenya

Publications

  1. ncbi request reprint The past, present and future of antifolates in the treatment of Plasmodium falciparum infection
    Alexis Nzila
    Kenya Medical Research Institute KEMRI Wellcome Trust Collaborative Research Program, PO Box 230, 80108, Kilifi, Kenya
    J Antimicrob Chemother 57:1043-54. 2006
  2. ncbi request reprint Inhibitors of de novo folate enzymes in Plasmodium falciparum
    Alexis Nzila
    Kenya Medical Research Institute KEMRI Wellcome Trust Collaborative Research Program, P O Box 230, 80108, Kilifi, Kenya
    Drug Discov Today 11:939-44. 2006
  3. pmc In vitro activities of piperaquine, lumefantrine, and dihydroartemisinin in Kenyan Plasmodium falciparum isolates and polymorphisms in pfcrt and pfmdr1
    Leah Mwai
    Kenya Medical Research Institute KEMRI Wellcome Trust Collaborative Research Program, Kilifi, Kenya
    Antimicrob Agents Chemother 53:5069-73. 2009
  4. doi request reprint Antimalarial activity of isoquine against Kenyan Plasmodium falciparum clinical isolates and association with polymorphisms in pfcrt and pfmdr1 genes
    John Okombo
    Kenya Medical Research Institute KEMRI Wellcome Trust Collaborative Research Program, PO Box 230, 80108 Kilifi, Kenya
    J Antimicrob Chemother 68:786-8. 2013
  5. pmc Chloroquine resistance before and after its withdrawal in Kenya
    Leah Mwai
    Kenya Medical Research Institute Wellcome Trust Collaborative Research Programme, Kilifi, Kenya
    Malar J 8:106. 2009
  6. pmc In vitro activities of quinine and other antimalarials and pfnhe polymorphisms in Plasmodium isolates from Kenya
    John Okombo
    Kenya Medical Research Institute KEMRI Wellcome Trust Collaborative Research Program, P O Box 230, 80108 Kilifi, Kenya
    Antimicrob Agents Chemother 54:3302-7. 2010
  7. pmc Declining responsiveness of Plasmodium falciparum infections to artemisinin-based combination treatments on the Kenyan coast
    Steffen Borrmann
    Kenya Medical Research Institute Wellcome Trust Research Programme, Kilifi, Kenya
    PLoS ONE 6:e26005. 2011
  8. pmc In vitro activity of antifolate and polymorphism in dihydrofolate reductase of Plasmodium falciparum isolates from the Kenyan coast: emergence of parasites with Ile-164-Leu mutation
    Steven M Kiara
    Kenya Medical Research Institute KEMRI Wellcome Trust Collaborative Research Program, P O Box 230, 80108 Kilifi, Kenya
    Antimicrob Agents Chemother 53:3793-8. 2009
  9. pmc Genome wide adaptations of Plasmodium falciparum in response to lumefantrine selective drug pressure
    Leah Mwai
    Kenya Medical Research Institute, Welcome Trust Research Programme, Kilifi, Kenya
    PLoS ONE 7:e31623. 2012
  10. pmc Baseline in vitro activities of the antimalarials pyronaridine and methylene blue against Plasmodium falciparum isolates from Kenya
    John Okombo
    Kenya Medical Research Institute KEMRI Wellcome Trust Collaborative Research Program, Kilifi, Kenya
    Antimicrob Agents Chemother 56:1105-7. 2012

Collaborators

Detail Information

Publications27

  1. ncbi request reprint The past, present and future of antifolates in the treatment of Plasmodium falciparum infection
    Alexis Nzila
    Kenya Medical Research Institute KEMRI Wellcome Trust Collaborative Research Program, PO Box 230, 80108, Kilifi, Kenya
    J Antimicrob Chemother 57:1043-54. 2006
    ..New concepts have been presented to improve antimalarial antifolate in vivo efficacy and to identify potent new antifolate agents...
  2. ncbi request reprint Inhibitors of de novo folate enzymes in Plasmodium falciparum
    Alexis Nzila
    Kenya Medical Research Institute KEMRI Wellcome Trust Collaborative Research Program, P O Box 230, 80108, Kilifi, Kenya
    Drug Discov Today 11:939-44. 2006
    ..If correct, this could lead to the identification of a new family of synergizers of DHFR inhibitors...
  3. pmc In vitro activities of piperaquine, lumefantrine, and dihydroartemisinin in Kenyan Plasmodium falciparum isolates and polymorphisms in pfcrt and pfmdr1
    Leah Mwai
    Kenya Medical Research Institute KEMRI Wellcome Trust Collaborative Research Program, Kilifi, Kenya
    Antimicrob Agents Chemother 53:5069-73. 2009
    ..Therefore, the use of LM-artemether is likely to lead to the selection of more CQ-susceptible parasites...
  4. doi request reprint Antimalarial activity of isoquine against Kenyan Plasmodium falciparum clinical isolates and association with polymorphisms in pfcrt and pfmdr1 genes
    John Okombo
    Kenya Medical Research Institute KEMRI Wellcome Trust Collaborative Research Program, PO Box 230, 80108 Kilifi, Kenya
    J Antimicrob Chemother 68:786-8. 2013
    ..Isoquine is one of these promising molecules that has already reached Phase I clinical trials in humans...
  5. pmc Chloroquine resistance before and after its withdrawal in Kenya
    Leah Mwai
    Kenya Medical Research Institute Wellcome Trust Collaborative Research Programme, Kilifi, Kenya
    Malar J 8:106. 2009
    ..Changes to those that occurred in the dihydrofolate reductase gene (dhfr) that confers resistance to the replacement drug, pyrimethamine/sulphadoxine were also compared...
  6. pmc In vitro activities of quinine and other antimalarials and pfnhe polymorphisms in Plasmodium isolates from Kenya
    John Okombo
    Kenya Medical Research Institute KEMRI Wellcome Trust Collaborative Research Program, P O Box 230, 80108 Kilifi, Kenya
    Antimicrob Agents Chemother 54:3302-7. 2010
    ..Two DNNND repeats combined with the pfmdr1-86 mutation could be used as an indicator of reduced susceptibility to quinine...
  7. pmc Declining responsiveness of Plasmodium falciparum infections to artemisinin-based combination treatments on the Kenyan coast
    Steffen Borrmann
    Kenya Medical Research Institute Wellcome Trust Research Programme, Kilifi, Kenya
    PLoS ONE 6:e26005. 2011
    ..The emergence of artemisinin-resistant P. falciparum malaria in South-East Asia highlights the need for continued global surveillance of the efficacy of artemisinin-based combination therapies...
  8. pmc In vitro activity of antifolate and polymorphism in dihydrofolate reductase of Plasmodium falciparum isolates from the Kenyan coast: emergence of parasites with Ile-164-Leu mutation
    Steven M Kiara
    Kenya Medical Research Institute KEMRI Wellcome Trust Collaborative Research Program, P O Box 230, 80108 Kilifi, Kenya
    Antimicrob Agents Chemother 53:3793-8. 2009
    ..We confirmed the presence of this mutation by sequencing. Thus, TMX and MTX are potent against P. falciparum, and quadruple mutants are now emerging in Africa...
  9. pmc Genome wide adaptations of Plasmodium falciparum in response to lumefantrine selective drug pressure
    Leah Mwai
    Kenya Medical Research Institute, Welcome Trust Research Programme, Kilifi, Kenya
    PLoS ONE 7:e31623. 2012
    ..falciparum LM susceptibility...
  10. pmc Baseline in vitro activities of the antimalarials pyronaridine and methylene blue against Plasmodium falciparum isolates from Kenya
    John Okombo
    Kenya Medical Research Institute KEMRI Wellcome Trust Collaborative Research Program, Kilifi, Kenya
    Antimicrob Agents Chemother 56:1105-7. 2012
    ..3 nM for pyronaridine and methylene blue, respectively. Their activities were not associated with polymorphisms in these genes. The drugs' high in vitro activities indicate that they would be efficacious against Kenyan isolates in vivo...
  11. pmc Preclinical evaluation of the antifolate QN254, 5-chloro- N'6'-(2,5-dimethoxy-benzyl)-quinazoline-2,4,6-triamine, as an antimalarial drug candidate
    Alexis Nzila
    Kenya Medical Research Institute Wellcome Trust Collaborative Research Program, Kilifi, Kenya
    Antimicrob Agents Chemother 54:2603-10. 2010
    ..Thus, despite its relative in vitro selectivity toward the Plasmodium DHFR enzyme, QN254 does not show the adequate therapeutic index to justify its further development as a single agent...
  12. pmc Anticancer agents against malaria: time to revisit?
    Alexis Nzila
    Kenya Medical Research Institute KEMRI Wellcome Trust Collaborative Research Programme, Kilifi, Kenya
    Trends Parasitol 26:125-9. 2010
    ..Thus, the opportunity exists to discover new antimalarials using the anticancer pharmacopoeia...
  13. doi request reprint Update on genetic markers of quinine resistance in Plasmodium falciparum
    John Okombo
    Kenya Medical Research Institute KEMRI Wellcome Trust Collaborative Research Program, Kilifi, Kenya
    Mol Biochem Parasitol 177:77-82. 2011
    ..Overall, quinine still remains efficacious in Africa, and pfnhe, the sodium hydrogen exchanger, may be one of the genetic markers underlying quinine in vitro resistance...
  14. pmc Effect of folate derivatives on the activity of antifolate drugs used against malaria and cancer
    Eunice Nduati
    Kenya Medical Research Institute Wellcome Trust Collaborative Research Program, PO Box 230, 80108 Kilifi, Kenya
    Parasitol Res 102:1227-34. 2008
    ..For instance, the combination of 5-Me-THF with a low dose of TMX could be used to treat malaria. In addition, the safety of a low dose of MTX in the treatment of arthritis indicates that this drug could be used alone to treat malaria...
  15. pmc A phase I trial to evaluate the safety and pharmacokinetics of low-dose methotrexate as an anti-malarial drug in Kenyan adult healthy volunteers
    Roma Chilengi
    Kenya Medical Research Institute KEMRI Wellcome Trust Research Programme, PO Box 230, 80108 Kilifi, Kenya
    Malar J 10:63. 2011
    ..A phase I evaluation was conducted to assess the safety and pharmacokinetic profile of this drug in healthy adult male Kenyan volunteers...
  16. pmc In vitro activities of 2,4-diaminoquinazoline and 2,4-diaminopteridine derivatives against Plasmodium falciparum
    Sheila Ommeh
    Kenya Medical Research Institute KEMRI Wellcome Trust Collaborative Research Program, Wellcome Trust Research Laboratories, P O Box 43640 GPO, 00100 Nairobi, Kenya
    Antimicrob Agents Chemother 48:3711-4. 2004
    ..Further studies are warranted to assess the therapeutic potential of this combination in vivo...
  17. doi request reprint In vivo and in vitro efficacy of amodiaquine against Plasmodium falciparum in an area of continued use of 4-aminoquinolines in East Africa
    Philip Sasi
    Kenya Medical Research Institute, Center for Geographic Medicine Research Coast, Kilifi, Kenya
    J Infect Dis 199:1575-82. 2009
    ..These findings also suggest that the value of amodiaquine combinations as first- or second-line treatment in areas with similar patterns of 4-aminoquinoline resistance should be reassessed...
  18. pmc In vitro selection of Plasmodium falciparum drug-resistant parasite lines
    Alexis Nzila
    Kenya Medical Research Institute KEMRI Wellcome Trust Collaborative Research Program, PO Box 230, 80108 Kilifi, Kenya
    J Antimicrob Chemother 65:390-8. 2010
    ..In this review, we discuss the key parameters that impact on the efficiency of the in vitro selection of resistance, and propose strategies to improve and streamline this process...
  19. pmc Comparative folate metabolism in humans and malaria parasites (part I): pointers for malaria treatment from cancer chemotherapy
    Alexis Nzila
    Kenya Medical Research Institute and Wellcome Trust Collaborative Research Program, Wellcome Trust Research Laboratories, PO Box 43640, Nairobi GPO 00100, Kenya
    Trends Parasitol 21:292-8. 2005
    ..We discuss how this information could lead to the identification of new targets in malaria parasites...
  20. ncbi request reprint Why has the dihydrofolate reductase 164 mutation not consistently been found in Africa yet?
    Alexis Nzila
    Kenya Medical Research Institute Wellcome Trust Collaborative Research Program, Wellcome Trust Research Laboratories, P O Box 43640, 00100 GPO, Nairobi, Kenya
    Trans R Soc Trop Med Hyg 99:341-6. 2005
    ..In this paper, we discuss briefly the reasons why Leu-164 has not yet been selected in Africa and we propose a means that may slow down the selection of this mutation...
  21. pmc Comparative folate metabolism in humans and malaria parasites (part II): activities as yet untargeted or specific to Plasmodium
    Alexis Nzila
    Kenya Medical Research Institute and Wellcome Trust Collaborative Research Program, Wellcome Trust Research Laboratories, PO Box 43640, Nairobi GPO 00100, Kenya
    Trends Parasitol 21:334-9. 2005
    ....
  22. pmc Chemosensitization of Plasmodium falciparum by probenecid in vitro
    Alexis Nzila
    Kenya Medical Research Institute Wellcome Trust Collaborative Research Program, Wellcome Trust Research Laboratories, Nairobi, Kenya
    Antimicrob Agents Chemother 47:2108-12. 2003
    ..P. Thompson & Co., Liverpool, United Kingdom] has been filed to protect this intellectual property)...
  23. doi request reprint Modulators of the efficacy and toxicity of drugs in malaria treatment
    Alexis Nzila
    Kenya Medical Research Institute KEMRI Wellcome Trust Collaborative Research Program, PO Box 230, 80108, Kilifi, Kenya
    Trends Pharmacol Sci 31:277-83. 2010
    ..In this review, we present evidence that the use of modulators of the efficacy and toxicity of drugs will lead to the discovery of new drugs and extend the therapeutic lifetime of existing agents...
  24. ncbi request reprint Short report: association between chloroquine and amodiaquine resistance and allelic variation in the Plasmodium falciparum multiple drug resistance 1 gene and the chloroquine resistance transporter gene in isolates from the upper Nile in southern Sudan
    Edwin O Ochong
    Kenya Medical Research Institute, Wellcome Trust Collaborative Program, Medecins Sans Frontieres Holland, South Sudan Section, Nairobi, Kenya
    Am J Trop Med Hyg 69:184-7. 2003
    ..The data show that the allele of the pfcrt gene with a lysine to threonine change at codon 76 is strongly associated with both chloroquine and amodiaquine resistance. No such association was observed with the pfmdr1 gene...
  25. ncbi request reprint Antimalarial chemotherapy: young guns or back to the future?
    Giancarlo A Biagini
    Division of Molecular and Biochemical Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
    Trends Parasitol 19:479-87. 2003
  26. pmc 2,4-diaminopteridine-based compounds as precursors for de novo synthesis of antifolates: a novel class of antimalarials
    Eunice Nduati
    Kenya Medical Research Institute KEMRI Wellcome Trust Collaborative Research Program, Wellcome Trust Research Laboratories, P O Box 43640, GPO 00100, Nairobi, Kenya
    Antimicrob Agents Chemother 49:3652-7. 2005
    ..If this hypothesis holds true, the de novo synthesis of the toxic compounds could be used as a framework for the search for novel potent antimalarial antifolates...
  27. ncbi request reprint Artemether/lumefantrine in the treatment of uncomplicated falciparum malaria
    Gilbert Kokwaro
    Kenya Medical Research Institute KEMRI Wellcome Trust Research Programme, Clinical Pharmacology Molecular Parasitology Section, PO Box 43640 00100, Nairobi, Kenya
    Expert Opin Pharmacother 8:75-94. 2007
    ....