In vitro evaluation of quinidine sensitivity in brazilian Plasmodium falciparum isolates: comparative analysis to quinine and chloroquine

Abstract

Falciparum malaria represents a serious and an increasing world public health problem due to the acquired parasite's resistance to the most available drugs. In some endemic areas, quinidine, a diastereoisomer of the antimalarial quinine, has been employed for replacing the latter. In order to evaluate the use of quinidine as an alternative to the increasing loss of quinine effectiveness in Brazilian P. falciparum strains, as has been observed in the Amazon area, we have assayed quinidine, quinine and chloroquine. The in vitro microtechnique was employed. All isolates showed to be highly resistant to chloroquine. Resistance to quinine was not noted although high MIC (minimal inhibitory concentration) values have been observed. These data corroborate the decreasing sensitivity to quinine in strains from Brazil. Quinidine showed IC50 from 0.053 to 4.577 micromol/L of blood while IC50 from 0.053 to 8.132 micromol/L of blood was estimated for quinine. Moreover, clearance of the parasitemia was observed in concentrations lower than that used for quinidine in antiarrhythmic therapy, confirming our previous data. The results were similar to African isolate.

Use of a colorimetric (DELI) test for the evaluation of chemoresistance of Plasmodium falciparum and Plasmodium vivax to commonly used anti-plasmodial drugs in the Brazilian Amazon

“…This was expected since earlier studies conducted in Amazonia suggested that 100% of the P. falciparum isolates circulating in the area were chloroquine-resistant [17]. In addition, most of the “sensitive” isolates had IC50s close to the threshold for sensitivity (100 nM) and therefore represent rather borderline isolates.…”

“…Some isolates showed IC50s very close to the threshold. In any case, this scenario is worrisome because a continuous decreasing in parasite sensitivity has been noted in the Brazilian Amazon [17,21,24-27] and quinine plus doxycycline is actually recommended as P. falciparum second-line treatment by the Brazilian Malaria Control Programme.…”

Atovaquone, chloroquine, primaquine, quinine and tetracycline: antiproliferative effects of relevant antimalarials on Neospora caninum

“…Interestingly, quinine has different effects against Plasmodium and T. gondii. Although quinine shows high activity in in vitro models of Plasmodium (0.272-5.2 μM, and 0.053-8.1 μM determined by (Touré et al, 2008), (Björkman et al, 1991) and (Menezes et al, 2001), no inhibitory effect on T. gondii has been reported (Gomes et al, 2012;Holfels et al, 1994). Against N. caninum, the activity of quinine was moderate (56.6 μM, Table 1 and Figure 1D).…”

Chemoresistance of Plasmodium falciparum and Plasmodium vivax parasites in Brazil: consequences on disease morbidity and control

“…In Brazil, P. falciparum in vitro tests have been performed since 1981 either alone (Ferraroni et al 1981, Reyes 1981, Couto et al 1995, Calvosa et al 2001, Menezes et al 2001, in conjunction with in vivo follow-up studies (Boulos et al 1986, Neifer & Kremsner 1991, Segurado et al 1997, Cerutti et al 1999b or along with molecular genotyping (Póvoa et al 1998, Zalis et al 1998, Vieira et al 2001.…”