Studies of resistance to chloroquine, quinine, amodiaquine and mefloquine among Philippine strains of Plasmodium falciparum

Abstract

One hundred cases of slide-confirmed Plasmodium falciparum malaria admitted to the San Lazaro Hospital, Manila, Philippines were screened for in vitro resistance to chloroquine, quinine, amodiaquine and mefloquine using the microtechnique. 59 of the 100 primary parasite isolates produced schizonts, whereas the remaining 41 isolates did not. 51 of the 59 isolates tested were resistant in vitro to chloroquine and eight were sensitive. In contrast, three of the primary isolates were resistant to quinine, three showed resistance to amodiaquine and four were mefloquine-resistant. 43 of the strains judged chloroquine-resistant in vitro were fully in vitro sensitive to amodiaquine, quinine and mefloquine. One chloroquine-resistant isolate was also resistant to quinine alone. Three isolates that were resistant to chloroquine were also resistant to amodiaquine. An additional three were cross-resistant to chloroquine and mefloquine. A single isolate was found to be resistant to chloroquine, quinine and mefloquine and another was cross-resistant to chloroquine, quinine and amodiaquine. All strains demonstrating in vitro resistance to amodiaquine, quinine or mefloquine also showed in vitro resistance to chloroquine. The parasites in 22 patients showed in vivo resistance to chloroquine therapy. 86% were of the R1 type, 9% were R2 and 5% R3. All 22 patients demonstrating in vivo resistance to chloroquine showed in vitro resistance.

Komplizierte Malaria tropica: spezifische und supportive Therapie bei importierten Erkrankungen

“…Bereits nach wenigen Stunden erzielten wir regelmäßig einen deutlichen Effekt. Wir sahen uns deshalb nicht veranlaßt, auf das Antiarrhythmikum Chinidin zurückzugreifen, obwohl es nach einzelnen Literaturberichten wirksamer sein soll (20 (17).…”

Antimalarial agents: mechanisms of action

“…This hypothesis is consistent with the morphologic observations of Jacobs et al (29), who have reported that the most striking ultrastructural change produced by mefloquine is swelling of the secondary lysosome (food vacuole) of the parasite. Although the nature of the interaction of mefloquine with the parasite vesicle is less well characterized than that of chloroquine, the parasite can become resistant to chloroquine alone, to mefloquine alone, or to both drugs (3, 20,36,58). Because the non-weak base effect (33)(34)(35) is observed with mefloquine in chloroquineresistant parasites, it is likely that the mechanism of chloroquine resistance is independent of the non-weak base effect.…”

A method for reducing the sloughing of thick blood films for malaria diagnosis

“…Under non-ideal field lab conditions, the estimated sensitivity is only 100-500 parasites/uL, which is comparable to the antigen-detection methods under similar conditions [4-6]. Unfortunately, a complication of thick film preparation in both laboratory and field settings is sloughing of some or the entire blood droplet during preparation, usually during the post-staining rinse [2,7-13]. Loss of sample during preparation may necessitate preparing a replacement slide, if additional sample blood is available, and delay diagnosis.…”

“…Loss of sample during preparation may necessitate preparing a replacement slide, if additional sample blood is available, and delay diagnosis. A number of suggestions for ameliorating blood droplet sloughing can be found in a review of the literature, including: 1) extended blood droplet drying times (up to 24 hours) [3,12,13]; 2) utilization of an oven or heatblock to dry the sample [3,9,14-16]; 3) brief washes in methanol or acetone to help dehydrate the sample [8,10,11]; and 4) use of very small blood volumes (<5 μL) to prepare the thick film in conjunction with an alternative staining procedure [16]. …”