In vitro activity of antimalarials against clinical isolates of Plasmodium falciparum in Yaounde, Cameroon

The in vitro activity of nine antimalarials was determined against 119 fresh clinical isolates of #Plasmodium falciparum$ obtained from symptomatic indigenous patients in Yaounde, Cameroun, using the isotopic semimicrotest. Seventy-four parasites were resistant to chloroquine (mean 50% inhibitory concentration [IC50] 337 nM) ; 45 were chloroquine-sensitive (mean IC50 35.6 nM). Twenty-five of 58 chloroquine-resistant parasites were resistant to monodesethylamodiaquine, the biologically active metabolite of amodiaquine. None of the chloroquine-sensitive isolates was resistant to monodesethylamodiaquine (IC50 17.3 nM). Pyronaridine, quinine, mefloquine, halofantrine, and artemether were highly active against the chloroquine-sensitive and the chloroquine-resistant isolates. Of the 43 isolates tested, 25 were sensitive to both pyrimethamine and cycloguanil, the biologically active metabolite of proguanil. The in vitro responses of chloroquine and monodesethylamodiaquine, chloroquine and quinine, quinine and mefloquine, mefloquine and halofantrine, artemether and mefloquine or halofantrine, and pyrimethamine and cycloguanil were significantly correlated. The present study suggests that chloroquine resistance is highly prevalent in vitro in Yaounde and that the alternative drugs are generally highly active against the chloroquine-resistant parasites. (Résumé d'auteur

Transmission blocking activity of a standardized neem (Azadirachta indica) seed extract on the rodent malaria parasite Plasmodium berghei in its vector Anopheles stephensi

<p>Abstract</p> <p>Background</p> <p>The wide use of gametocytocidal artemisinin-based combination therapy (ACT) lead to a reduction of <it>Plasmodium falciparum </it>transmission in several African endemic settings. An increased impact on malaria burden may be achieved through the development of improved transmission-blocking formulations, including molecules complementing the gametocytocidal effects of artemisinin derivatives and/or acting on <it>Plasmodium </it>stages developing in the vector. Azadirachtin, a limonoid (tetranortriterpenoid) abundant in neem (<it>Azadirachta indica</it>, Meliaceae) seeds, is a promising candidate, inhibiting <it>Plasmodium </it>exflagellation <it>in vitro </it>at low concentrations. This work aimed at assessing the transmission-blocking potential of NeemAzal^®, an azadirachtin-enriched extract of neem seeds, using the rodent malaria <it>in vivo </it>model <it>Plasmodium berghei</it>/<it>Anopheles stephensi</it>.</p> <p>Methods</p> <p><it>Anopheles stephensi </it>females were offered a blood-meal on <it>P. berghei </it>infected, gametocytaemic BALB/c mice, treated intraperitoneally with NeemAzal, one hour before feeding. The transmission-blocking activity of the product was evaluated by assessing oocyst prevalence, oocyst density and capacity to infect healthy mice. To characterize the anti-plasmodial effects of NeemAzal^®on early midgut stages, i.e. zygotes and ookinetes, Giemsa-stained mosquito midgut smears were examined.</p> <p>Results</p> <p>NeemAzal^®completely blocked <it>P. berghei </it>development in the vector, at an azadirachtin dose of 50 mg/kg mouse body weight. The totally 138 examined, treated mosquitoes (three experimental replications) did not reveal any oocyst and none of the healthy mice exposed to their bites developed parasitaemia. The examination of midgut content smears revealed a reduced number of zygotes and post-zygotic forms and the absence of mature ookinetes in treated mosquitoes. Post-zygotic forms showed several morphological alterations, compatible with the hypothesis of an azadirachtin interference with the functionality of the microtubule organizing centres and with the assembly of cytoskeletal microtubules, which are both fundamental processes in <it>Plasmodium </it>gametogenesis and ookinete formation.</p> <p>Conclusions</p> <p>This work demonstrated <it>in vivo </it>transmission blocking activity of an azadirachtin-enriched neem seed extract at an azadirachtin dose compatible with 'druggability' requisites. These results and evidence of anti-plasmodial activity of neem products accumulated over the last years encourage to convey neem compounds into the drug discovery & development pipeline and to evaluate their potential for the design of novel or improved transmission-blocking remedies.</p

In-vitro activity of primaquine against the asexual blood stages of Plasmodium falciparum

The in vitro activities of dihydroartemisinin (the biologically active metabolite of artemisinin derivatives), chloroquine, monodesethylamodiaquine (the biologically active metabolite of amodiaquine), quinine, mefloquine, halofantrine, and pyrimethamine were assessed in 65 African isolates of #Plasmodium falciparum$ from Yaoundé, Cameroon using an isotopic microtest. The 50% inhibitory concentration (IC50) values for dihydroartemisinin were within a narrow range from 0.25 to 4.56 nM, with a geometric mean of 1.11 nM (95%) confidence interval = 0.96-1.28 nM). Dihydroartemisinin was equally active (P is greater than 0.05) against the chloroquine-sensitive isolates (geometric mean IC50 = 1.25 nM, 95% confidence interval ) 0.99-157 nM) and the chloroquine-resistant isolates (geometric mean IC50 = 0.979 nM, 95% confidence interval = 0.816-1.18 nM). A significant positive correlation was observed between the responses to dihydroartemisinin and mefloquine (r - 0.662) or halofantrine (r = 0.284), suggesting in vitro cross-resistance. There was no correlation between the responses to dihydroaertemisinin and other antimalarial drugs. ((Résumé d'auteur

Antimalarial activity in crude extracts of some Cameroonian medicinal plants

Fifteen crude extracts from the stem bark and seeds of four medicinal plants, viz: Entandrophragma angolense, Picralima nitida, Schumanniophyton magnificum and Thomandersia hensii were tested in vitro for their antimalarial activity against the chloroquine-resistant Plasmodium falciparum W2 strain. The results showed that the extracts of these plants possessed some antimalarial activity, the methanol extract of Picralima nitida demonstrating the highest activity in vitro. Further isolation and identification of some active compounds from these plants will justify their common use in traditional medicine for the treatment of malaria or fever in Cameroon.Keywords: Entandrophragma angolense; Picralima nitida; Schumanniophyton magnificum; Thomandersia hensii; Plasmodium falciparum; Antimalarial activity The African Journal of Traditional, Complementary and Alternative Medicines Vol. 4 (1) 2007: pp. 107-11