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At least 1,423 records · Page 79Linked to original sources
PubMed1987

In vitro susceptibility of Plasmodium falciparum isolates from Jilore, Kenya, to antimalarial drugs.

Twenty-six Plasmodium falciparum isolates obtained during a prophylaxis study at Jilore primary school, Malindi, Kenya, were adapted to in vitro culture and their susceptibility to 13 antimalarial drugs was tested by a modified radioisotopic method. Pyrimethamine, chloroquine, amodiaquine, cycloguanil, chlorcycloguanil, quinine, quinidine and sulfadoxine, and the experimental compounds MB 35769, mefloquine, WR 184806, parvoquone, and menoctone were used. The isolates could be divided into two groups with significantly different susceptibility to pyrimethamine, shown by a 755-fold difference in the mean ID50 values (2.77 +/- 1.98 x 10(-10) mol/l and 2.09 +/- 1.64 x 10(-7) mol/l). The mean susceptibility of the two groups differed 7.7-fold for chlorcycloguanil and 14.6-fold for cycloguanil, but were not significantly different for the other drugs. All isolates were more sensitive to amodiaquine than to chloroquine in vitro. The ratio of the geometric mean ID50 values of chloroquine to amodiaquine was 3.13. The ratio for the chemically related compounds parvoquone to menoctone was 5.63, quinine to quinidine was 5.58, and mefloquine to WR 184806 was 12.16.

Animals↗
PubMed1988

Analysis of dose-response curves for the in vitro susceptibility of Plasmodium falciparum to antimalarials using a pocket computer.

A small pocket computer, Sharp PC-1500, was programmed to analyze the dose-response curves generated by the in vitro assay of antimalarials against field isolates of Plasmodium falciparum. Using nonlinear regression the analysis provided an estimate of the 50% inhibitory concentration with 95% confidence limits and a graph of the data points and regression function line. The pocket computer with the nonlinear regression program offers a powerful, portable, and inexpensive data analysis system suitable for field use.

Animals↗
PubMed1989

Stage specific actions of antimalarial drugs on Plasmodium falciparum in culture.

Chemicals with antimalarial effects show different patterns against ring stages, trophozoites, and schizonts of Plasmodium falciparum in culture. Amodiaquine, mefloquine, quinine, quinacrine, primaquine, qinghaosu, halofantrine, rifampin, antimycin A1, cycloheximide, and actinomycin D were preferentially toxic to the mature stages. Ammonium chloride killed ring stages faster than mature forms, while tetracycline, clindamycin, and halofuginone acted with equal speed on all 3 stages.

Animals↗
PubMed1990

Gametocytocidal activity of the antimalarial alpha/beta arteether against Plasmodium cynomolgi B.

A new sesquiterpene lactone alpha/beta arteether (a 30:70 mixture of enantiomers), which possesses very high blood schizontocidal activity, has been evaluated for gametocytocidal/sporontocidal action against Plasmodium cynomolgi B infection in the rhesus monkey. This paper reports gametocytocidal action of this new antimalarial drug at 2.5-5 mg/kg (single im dose) against P. cynomologi B as shown by the complete absence of mosquito infectivity. No sporontocidal action was demonstrable in the vector at a dose of up to 20-50 mg/kg im.

Animals↗
PubMed1992

Daphnetin: a novel antimalarial agent with in vitro and in vivo activity.

Daphnetin is a dihydroxycoumarin that is being used in China for the treatment of coagulation disorders. It is also a chelator and an antioxidant. In vitro, daphnetin causes a 50% inhibition (IC50) of 3H-hypoxanthine incorporation by Plasmodium falciparum at concentrations between 25 and 40 microM. Several related compounds, such as scopoletin, 2, 3-dihydroxybenzoic acid and 3, 4-dihydroxybenzoic acid show no inhibitory activity. The antimalarial activity of daphnetin is inhibited by the addition of iron. Daphnetin does not appear to be an oxidant drug, since it does not spontaneously generate superoxide in vitro. However, it does alkylate bovine serum albumin when incubated in the presence of iron. In vivo, daphnetin significantly prolongs survival of P. yoelli-infected mice.

Animals↗
PubMed1992

In vitro activity of halofantrine and its relationship to other standard antimalarial drugs against African isolates and clones of Plasmodium falciparum.

The in vitro activity of halofantrine was studied in chloroquine-susceptible and chloroquine-resistant African clones of Plasmodium falciparum over a period of six months. The susceptibility level remained stable in both clones. The chloroquine-susceptible clone (50% inhibitory concentration [IC50] 6.88 nM) was less susceptible to halofantrine than the chloroquine-resistant clone (IC50 2.98 nM). Using an isotopic semimicro drug susceptibility test, the in vitro activity of halofantrine was compared with the activities of chloroquine, quinine, and mefloquine to study the cross-resistance patterns against 76 African isolates of P. falciparum isolated from cases of malaria imported into France. Chloroquine-resistant isolates (n = 47) were significantly less susceptible to quinine (IC50 234 nM), but were more susceptible to both mefloquine (IC50 3.20 nM) and halofantrine (IC50 1.14 nM) compared with the chloroquine-susceptible isolates (n = 29; IC50 147 nM for quinine, 7.16 nM for mefloquine, and 2.62 nM for halofantrine). A significant positive correlation was found between the activities of chloroquine and quinine and between those of mefloquine and halofantrine, indicating cross-resistance between these drugs, while a negative correlation was observed between chloroquine and mefloquine or halofantrine. The responses to quinine and mefloquine or halofantrine showed no correlation with each other. These results reinforce the importance of a cautious use of antimalarial drugs in Africa.

Africa↗
PubMed1994

New, antimalarial, tricyclic 1,2,4-trioxanes: evaluations in mice and monkeys.

We have concluded initial preclinical studies with synthetic trioxanes numbered 3-9 and have compared them with artemisinin (numbered 1) using CD-1 mice infected with Plasmodium berghei. Based on their antimalarial effectiveness in mice, two of these synthetic trioxanes were selected for evaluation in Aotus monkeys infected with multidrug-resistant (MDR) P. falciparum. Trioxane numbered 8 (12 and 48 mg/kg), trioxane numbered 9 (12 and 48 mg/kg) and arteether (numbered 2, 48 mg/kg) were administered intramuscularly in three 12-hr doses to A. lemurinus lemurinus (Panamanian owl monkeys) infected with the Vietnam Smith/RE strain of P. falciparum and monitored for parasitemia. Trioxane numbered 8 at 12 mg/kg cleared parasitemia in two monkeys, but recrudescence occurred in one animal. Treatment of the recrudescent infection with 48 mg/kg was curative. Infections in two monkeys treated initially with 48 mg/kg were cured (six-month follow-up). Trioxane numbered 9 produced a similar outcome: 12 mg/kg suppressed parasitemia in two monkeys but was not curative; however, 48 mg/kg cured infections in all four monkeys treated. These preliminary observations show synthetic trioxanes numbered 8 and 9 to be as effective as arteether (numbered 2) against MDR in P. falciparum in the Aotus monkey.

Animals↗
PubMed1994

The efficacy of antimalarial regimens containing sulfadoxine-pyrimethamine and/or chloroquine in preventing peripheral and placental Plasmodium falciparum infection among pregnant women in Malawi.

To define an effective and deliverable antimalarial regimen for use during pregnancy, pregnant women at highest risk of malaria (those in their first or second pregnancy) in an area of Malawi with high transmission of chloroquine (CQ)-resistant Plasmodium falciparum were placed on CQ and/or sulfadoxine-pyrimethamine (SP). Of 38 pregnant women who received CQ treatment followed by weekly CQ prophylaxis (CQ/CQ) for at least 45 days prior to delivery, 32% had placental malaria infection, compared with 26% of 50 pregnant women who received a treatment dose of SP followed by weekly CQ prophylaxis (SP/CQ), and only 9% of 71 pregnant women who received a two-dose SP regimen (SP/SP; given once during the second trimester and repeated at the beginning of the third trimester) (P = 0.006, by chi-square test). During the peak transmission season from April to July, 47% of the women who received CQ/CQ had placental malaria infection at delivery, as compared with 37% of the women who received SP/CQ, and 10% of women who received SP/SP (P = 0.004, by chi-square test). Among women in their first or second pregnancy, two treatment doses of SP were highly effective in decreasing the proportion of women with placental malaria infection at delivery.

Analysis of Variance↗
PubMed1996

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, Cameroon. 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.

Animals↗
PubMed1999

The antimalarial triazine WR99210 and the prodrug PS-15: folate reversal of in vitro activity against Plasmodium falciparum and a non-antifolate mode of action of the prodrug.

We have studied the reversal of activity against Plasmodium falciparum of WR99210, a triazine antimalarial drug, and of the pro-drug PS-15 by folic acid (FA) and folinic acid (FNA). Folic acid and FNA inhibit the growth of P. falciparum in vitro at concentrations > 10(-4.5) and 10(-3.5) mol/L, respectively. The activity of pyrimethamine against Kenyan strains M24 and K39 is reduced 10-12-fold by 10(-5) mol/L of FA, and virtually eliminated by 10(-5) mol/L of FNA. Folates do not antagonise the action of WR99210 against Kenyan strains, and only partially antagonize the action of WR99210 action against the Southeast Asian strains V1/S and W282. Similarly, FA and FNA exerted weak or no antagonism of the action of PS-15. The inability of folates to antagonize the action of WR99210 can be explained in terms of high drug-enzyme affinity, but this does not account for the inability of FA and FNA to antagonize PS-15. These results suggest that action of PS-15 against P. falciparum is primarily due to a non-folate mechanism.

Animals↗
PubMed1999

No evidence of cardiotoxicity during antimalarial treatment with artemether-lumefantrine.

Artemether-lumefantrine is a new fixed antimalarial combination effective against multidrug-resistant falciparum malaria. A prospective electrocardiographic study was conducted in 150 patients receiving artemetherlumefantrine and 50 treated with artesunate-mefloquine. There was no evidence for clinically significant changes in the electrocardiographic intervals and in particular no relationship between plasma concentrations of lumefantrine and QTc prolongation. Artemether-lumefantrine does not have significant cardiac effects at therapeutic doses.

Adolescent↗
PubMed2002

Comparison of the cardiac effects of the antimalarials co-artemether and halofantrine in healthy participants.

Co-artemether (Coartem, Riamet) is a tablet containing 20 mg artemether and 120 mg lumefantrine for treatment of falciparum malaria. Lumefantrine has some chemical similarities to halofantrine (Halfan), an antimalarial known for QTc prolongation. Effects on the QTc interval of fed single oral doses of 500 mg halofantrine and 80/480 mg co-artemether were compared in 13 healthy males in a randomized double-blind crossover study. Electrocardiograms (ECGs) were recorded from 48 hours before dosing until 48 hours thereafter. The maximum QTc interval (QTc = QT/square root(RR)) was compared before and after treatment and between treatments, fitting a general linear model. Drug plasma concentrations were determined concomitantly. After halofantrine, all participants showed an increase in the QTc interval; the mean maximum increase was 28 ms. The length of the QTc interval was positively correlated to halofantrine exposure. The QTc interval remained unchanged after co-artemether. The difference between treatments was statistically significant. In conclusion, halofantrine caused a significant, exposure-dependent increase in the QTc interval. No such effect was seen with co-artemether.

Administration, Oral↗
PubMed1998

[The proper use of antimalarial drugs currently available].

French medical practitioners have at their disposal several antimalarial drugs for giving chemoprophylaxis to people travelling to a malaria endemic country or treating an imported malaria case in a patient. The choice depends on the contre-indications and indications of each drug, essentially subordinated to the presence and level of Plasmodium falciparum chemosensitivity in the visited area. For prevention, chloroquine alone can be taken in the areas where P. falciparum is absent or not chloroquine resistant; elsewhere, the choice between chloroquine/proguanil or mefloquine depends on knowing the prevalence and level of falciparum chloroquine resistance in these areas. For treatment, the only indications of chloroquine are imported malaria cases either due to P. vivax, P. ovale or P. malariae, or caused by P. falciparum contracted in one of the rare countries where the species is still sensitive to chloroquine. For uncomplicated falciparum malaria cases acquired in a chemoresistance area, mefloquine, halofantrine, sulfadoxine-pyrimethamine or oral quinine is selected, depending on the observed chemoprophylaxis, the contra-indications and the suspicion of chemoresistance type. Whatever the provenance area, P. falciparum in a patient with one or several serious symptoms or possibly profuse vomiting is treated by intravenous quinine, associated with tetracycline if the patient comes from an area known for a low quinine sensitivity of this species. The spectrum of falciparum malaria treatment has recently broadened to include new drugs such as artemisinin, artemether or atovaquone/proguanil, the latter being as yet unauthorized in France.

Animals↗
PubMed1999

Response of falciparum malaria to different antimalarials in Myanmar.

The purpose of the study was to ascertain the therapeutic efficacy of different treatments for uncomplicated falciparum malaria in the hospitals in Sagaing, northern and eastern Shan, to facilitate updating the existing national antimalarial drug policy. The proposed 14-day trial for monitoring the efficacy of treatments of uncomplicated falciparum malaria is an efficient method for identifying treatment failure patterns at the intermediate level (township hospital) in the Union of Myanmar. Minimal clinical and parasitological data for days 0-14 were required to classify treatment failure and success. Clinical and parasitiological responses on day 3 and days 4-14 were used as clear examples of early and late treatment failure, respectively. Mefloquine is five times more likely to be effective than chloroquine and sulfadoxine pyrimethamine (S-P), whereas chloroquine and S-P treatments have nearly identical failure patterns. The alarming frequency of clinical and parasitological failure (failure rate > 50%) following chloroquine treatment was reported in Sagaing and following S-P treatment in Sagaing and eastern Shan.

Adolescent↗
PubMed1999

Conformation of epicinchonine and cinchonine in view of their antimalarial activity: x-ray and theoretical studies.

X-ray structure analysis was carried out for a single crystal of 9-epi-10,11-dihydrocinchonine in the form of free base obtained by stereoselective interconversion of cinchonine via 9-O-tosylcinchonine. An intramolecular hydrogen bond was found between the carbinol hydroxyl group, -O12-H12, and the quinuclidine nitrogen atom, N1, with the parameters: O12...N1=2.688(3)A, O12-H12=0.84(4)A, N1...H12=2.11(4)A and O12-H12...N1=126(3) degrees. Theoretical calculations for isolated molecules of epicinchonine and cinchonine with the use of AM1 semiempirical method and comparative studies of the crystal structures have shown that the conformation of the alkaloid molecules with respect to the C8-C9 bond depends on the absolute configuration at C9. The conformation with respect to the C9-C16 bond depends on the protonation of N1 for threo but not for erythro alkaloids. It was established that the ability to form inter- or intramolecular hydrogen bonds is determined by the energetically preferred conformations of erythro and threo alkaloids, respectively. In most cases the conformations preferred for erythro alkaloids are energetically forbidden for their threo epimers and vice versa. The differences in conformation and capability to form intramolecular hydrogen bonds may explain why their antimalarial activities are incomparable.

Alkaloids↗
PubMed1998

Monitoring efficacy of commonly used antimalarials by a 14-day in-vivo test in a new settler's camp in endemic zone at Cox's Bazar.

The study was done in a new settler's camp "Barachara" under Sadar thana of Cox's Bazar district. It has a total population of 784 of all age groups, registered in the middle of the study period. A prospective evaluation of all cases of fever were done over 12 months, to see the pattern of febrile illness among the population and to compare the therapeutic efficacy of two alternative drug regimens for uncomplicated falciparum malaria (UM). Blood for malarial parasite (MP) was done in all cases of fever and was treated in line with the new clinical case definitions and treatment guidelines for malaria in Bangladesh. Slide positive UM cases were subjected to a "14-day in-vivo test" for therapeutic efficacy testing of antimalarial agents. The two drug regimens were randomised by lottery--a) 3 days oral chloroquine plus single dose sulphadoxin/pyrimethamine (CQ + SP) and, b) 3 days oral quinine plus single dose sulphadoxin/pyrimethamine (Q3 + SP). Drug administration was supervised by the field assistant and was followed up on days 3, 7 and 14 for blood slide examinations and clinical assessment. Sensitive response was observed in 79% of the cases in the CQ + SP group and 84% in the Q3 + SP group. Early treatment failure (persistently febrile and parasitaemic on days 3 or 7) was observed in 16% in the CQ + SP group and 9% in the Q3 + SP group. Both the evaluated drug regimens had less than 20% failures and can be used as alternative first line agents and Q3 + SP regimens can also be used as the second line agents for treatment failure (to chloroquine and/or SP) UM cases in the study area.

Adolescent↗