Diminished Plasmodium falciparum sensitivity to quinine exposure in vitro and in a sequential multi-drug regimen: A preliminary investigation in Guyana, South America.
OBJECTIVE
This preliminary study sought to investigate the response of uncomplicated falciparum infections to semi-supervised drug administration with quinine and two adjunctive schizontocidal drugs in infected patients in Guyana. Quinine and chloroquine cross-sensitivity was also assessed in vitro.


METHODS
Patients were treated with quinine 10mg/kg for 7 days followed by sulfadoxine/pyrimethamine 25mg/kg single dose (in children) or doxycycline 100mg daily for 7 days (in adults). Independently, falciparum-infected blood-medium mixtures were cultured in standardized pre-dosed quinine and chloroquine test plates, according to the protocol of the World Health Organization Mark III in vitro test system, for analysis.


RESULTS
The quinine/doxycycline regimen (N=12) produced 100% clinical cure (12/12) at day 14 and 100% parasitological cure (11/11) at day 28. However, with the quinine/sulfadoxine/pyrimethamine scheme, 1/12 therapeutic failure (on day 14) and 2/9 parasitological failures (on day 28) were observed. In vitro, parasite development beyond the cut-off concentrations and high IC(50) values (geometric mean IC(50) quinine 504.65nM and IC(50) chloroquine 506.69nM), confirmed diminished Plasmodium falciparum sensitivity to both drugs.


CONCLUSIONS
These findings suggest P. falciparum resistance to both quinine and chloroquine, and support either the use of antibiotics as adjuncts to quinine therapy or drugs with alternate pharmacodynamics as first-line therapy.
Best Plummer
Wallis
W
Department of Pharmacy, Faculty of Health Sciences, University of Guyana, Georgetown, Guyana. wsb2000@yahoo.com
Pinto Pereira
Lexley
L
D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D002738:Chloroquine / Q000494:pharmacology; D004318:Doxycycline / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D006172:Guyana; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D011739:Pyrimethamine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011803:Quinine / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D013413:Sulfadoxine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
D000962:Antimalarials; D013413:Sulfadoxine; D002738:Chloroquine; D011803:Quinine; D004318:Doxycycline; D011739:Pyrimethamine