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At least 1,261 records · Page 70Linked to original sources
PubMed1998

Recurrence of blackwater fever: triggering of relapses by different antimalarials.

Five cases of blackwater fever (BWF) are described, all of whom had a history of recent quinine therapy. In two cases a second haemolytic crisis was induced by halofantrine, in one case also a third. Increasing frequency of this syndrome with its dramatic clinical presentation is to be expected as imported P. falciparum infection, parasite resistance to chloroquine and the use of quinine and other related antimalarials become more frequent.

Adult↗
PubMed2000

Using evidence to change antimalarial drug policy in Kenya.

Chloroquine resistance was first detected in Kenya in 1978 and escalated during the 1980s. Chloroquine remained the treatment of choice for uncomplicated malaria infections until revised guidelines were launched in 1998 despite a plethora of scientific evidence on failure. This review analyses the range and quality of the evidence base that was used to change the drug policy in Kenya from chloroquine to SP and examines the process of consensus building and decision making. Our review illustrates the difficulties in translating sensitivity data with gross geographical, temporal and methodological variations into national treatment policy. The process was complicated by limited options, unknown adverse effects of replacement therapies, cost, as well as limited guidance on factors pertinent to changing the drug policy for malaria. Although > 50% of the studies showed parasitological failures by 1995, there was a general lack of consensus on the principles for assessing drug failures, the inclusion criteria for the study subjects and the relative benefits of parasitological and clinical assessments. A change in international recommendations for assessment of drug efficacy in 1996 from parasitological to clinical response further perplexed the decisions. There is an urgent need for international standards and evidence-based guidelines to provide a framework to assist the process by which decision-makers in malaria-endemic countries can make rational choices for antimalarial drug policy change.

Antimalarials↗
PubMed2001

Therapeutic efficacy of sulphadoxine/pyrimethamine and susceptibility in vitro of P. falciparum isolates to sulphadoxine-pyremethamine and other antimalarial drugs in Malawian children.

Since 1993 sulphadoxine/pyrimethamine (SP) has been used as the first-line drug for uncomplicated Plasmodium falciparum malaria in Malawi. To investigate the current efficacy of SP and other antimalarial drug resistance, we studied in vivo and in vitro responses to SP, chloroquine (CQ), mefloquine (MF), quinine (QN), and halofantrine (HF) in Salima, central Malawi. In a follow-up of 14 days, nine (13.8%) of 65 children under five showed RII/RIII parasitological resistance, and in in vitro microtests 18 (62.1%) of 29 isolates showed < 90% inhibition of schizont maturation at pyrimethamine 75 nmol/l blood medium mixture, indicating resistance. The discrepancy between in vivo and in vitro results might be partially explained by acquired immunity in this holoendemic area. In vitro one (3.4%) of 29 isolates failed schizont inhibition at 1.6 micromol/l blood of CQ, indicating resistance. Compared with an in vitro study conducted in 1988 in another region of Malawi using the same cut-off point, the proportion of resistant isolates had decreased significantly (P < 0.01). Although 31% of isolates were borderline, showing schizont maturation at 0.8 micromol/l blood but no schizonts at 1.6 micromol/l in our study, the results suggest possible recovery of CQ sensitivity after long-term absence of drug pressure. Resistance remains a major problem in malaria control. Monitoring resistance patterns in vitro provides early warning signs of impending loss of therapeutic efficacy of the standard treatment, and may detect changing patterns in alternative drug resistance.

Animals↗
PubMed2003

Plasmodium falciparum gametocytaemia in Nigerian children: before, during and after treatment with antimalarial drugs.

We evaluated gametocyte carriage and intensities of gametocytaemia in 710 children presenting with acute, symptomatic, uncomplicated Plasmodium falciparum malaria who were treated with various antimalarial drug regimens: chloroquine (CQ); chloroquine plus chlorpheniramine, a histamine H1 receptor antagonist that reverses CQ resistance in P. falciparum in vitro and in vivo (CQCP); chloroquine plus ketotifen, a histamine H1 receptor antagonist that reverses CQ resistance in P. falciparum in vitro but not in vivo in the present study (CQK); chloroquine plus pyrimethamine-sulphadoxine (CQPS); amodiaquine (AQ); amodiaquine plus pyrimethamine-sulphadoxine (AQPS); and pyrimethamine-sulphadoxine (PS). On presentation, gametocyte carriage was significantly higher in CQ-resistant (CQ-R) than in CQ-sensitive (CQ-S) infections. Following CQ treatment, gametocyte carriage was significantly higher at all times after treatment and gametocyte density significantly higher on day 7 of follow-up in children with CQ-R than CQ-S infections. CQ treatment of CQ-R infections resulted in significantly higher density of gametocytaemia on day 7 compared with pre-treatment (day 0), but similar treatment of CQ-S infections resulted in significantly lower density of gametocytaemia on day 14 compared with day 0. Among children with CQ-R infections, those with mild (RI) resistance carried gametocytes significantly more often than those with moderate (RII) resistance on days 5 and 7 of follow-up (P = 0.04 and 0.01, respectively). Disposition kinetics of gametocytaemia using a non-compartmental method showed that the half life of gametocytaemia was longer and the clearance slower in children with CQ-R than in those with CQ-S infections. PS treatment was associated with significantly higher gametocyte carriage at all times between days 1 and 14, and significantly higher gametocytaemias on days 7 and 14 than in the other treatment regimens. Combination of AQ with PS significantly decreased gametocyte carriage at all times between days 1 and 14 of follow-up. Continuing use of CQ in CQ-R infections may encourage transmission of CQ-R infections; SP monotherapy is associated with significant gametocyte carriage and gametocytaemia and may encourage transmission of SP resistant infections as resistance to the drug increases.

Age Factors↗
PubMed2003

The mechanisms of resistance to antimalarial drugs in Plasmodium falciparum.

Drug-resistant malaria is primarily caused by Plasmodium falciparum, a species highly prevalent in tropical Africa, the Amazon region and South-east Asia. It causes severe fever or anaemia that leads to more than a million deaths each year. The emergence of chloroquine resistance has been associated with a dramatic increase in malaria mortality among inhabitants of some endemic regions. The rationale for chemoprophylaxis is weakening as multiple-drug resistance develops against well-tolerated drugs. Plasmodium falciparum drug-resistant malaria originates from chromosome mutations. Analysis by molecular, genetic and biochemical approaches has shown that (i). impaired chloroquine uptake by the parasite vacuole is a common characteristic of resistant strains, and this phenotype is correlated with mutations of the Pfmdr1, Pfcg2 and Pfcrt genes; (ii). one to four point mutations of dihydrofolate reductase (DHFR), the enzyme target of antifolates (pyrimethamine and proguanil) produce a moderate to high level of resistance to these drugs; (iii). the mechanism of resistance to sulfonamides and sulfones involves mutations of dihydropteroate synthase (DHPS), their enzyme target; (iv). treatment with sulphadoxine-pyrimethamine selects for DHFR variants Ile(51), Arg(59), and Asn(108) and for DHPS variants Ser(436), Gly(437), and Glu(540); (v) clones that were resistant to some traditional antimalarial agents acquire resistance to new ones at a high frequency (accelerated resistance to multiple drugs, ARMD). The mechanisms of resistance for amino-alcohols (quinine, mefloquine and halofantrine) are still unclear. Epidemiological studies have established that the frequency of chloroquine resistant mutants varies among isolated parasite populations, while resistance to antifolates is highly prevalent in most malarial endemic countries. Established and strong drug pressure combined with low antiparasitic immunity probably explains the multidrug-resistance encountered in the forests of South-east Asia and South America. In Africa, frequent genetic recombinations in Plasmodium originate from a high level of malaria transmission, and falciparum chloroquine-resistant prevalence seems to stabilize at the same level as chloroquine-sensitive malaria. Nevertheless, resistance levels may differ according to place and time. In vivo and in vitro tests do not provide an adequate accurate map of resistance. Biochemical tools at a low cost are urgently needed for prospective monitoring of resistance.

Africa↗
PubMedDate not supplied

Aminopeptidase of Eimeria nieschulzi physico-chemical properties and action of antimalarial drugs.

An aminopeptidase capable of degrading synthetic substrates and short peptides has been demonstrated in Eimeria nieschulzi sporulated oocysts. Physico-chemical properties and the classic activator and inhibitory effects have been determined. The inhibitory activity of classic antimalarial drugs has been demonstrated and the study of the inhibitory mechanism by Chloroquine has been further studied. Lastly, the comparison between the aminopeptidase of Eimeria genus parasites and that of Plasmodium has been discussed.

Aminopeptidases↗
PubMed1990

Plasmodium: resistance to antimalarial drugs.

Quinine-resistant Plasmodium falciparum was first reported in 1910 from Brazil. Today this parasite is resistant in most endemic areas to the widely used blood schizonticide, chloroquine. Many strains are resistant also to antifols (e.g. pyrimethamine, proguanil) and some are also no longer eliminated by quinine. These polyresistant parasites have an enhanced ability to resist also new drugs such as mefloquine and halofantrine. There are indications that P. vivax is also becoming resistant to chloroquine in Papua-New Guinea where primaquine resistance of the hypnozoites also exists. The modes of action of antimalarials and mechanisms by which parasites become resistant to them are discussed. Future developments include the search for radically new compounds, for drugs that reverse chloroquine resistance and for new strategies to impede the progress of this problem.

Animals↗
PubMed2001

The apicoplast as an antimalarial drug target.

Resistance to commonly used malaria drugs is spreading and new drugs are required urgently. The recent identification of a relict chloroplast (apicoplast) in malaria and related parasites offers numerous new targets for drug therapy using well-characterized compounds. The apicoplast contains a range of metabolic pathways and housekeeping processes that differ radically to those of the host thereby presenting ideal strategies for drug therapy. Indeed, many compounds targeting these plastid pathways are antimalarial and have favourable profiles based on extensive knowledge from their use as antibacterials.

Animals↗
PubMed2005

Synthesis and antimalarial activity of new 3-arylquinoxaline-2-carbonitrile derivatives.

New series of 3-arylquinoxaline-carbonitrile derivatives have been synthesized from various 5-substituted or 5,6-disubstituted benzofuroxanes and tested for their in vitro and in vivo activity against the erythrocytic development of Plasmodium falciparum strain with different chloroquine-resistance status. Quinoxaline 1,4-dioxide derivatives showed superior antimalarial activity in respect to reduced quinoxaline analogues. The best activity was observed with nonsubstituted quinoxaline 1,4-dioxides in positions 6 and 7 of the aromatic ring and with a hydrogen or chloro substituent in para position of the phenyl group.

Animals↗
PubMed2002

Possible artefacts in the in vitro determination of antimalarial activity of natural products that incorporate into lipid bilayer: apparent antiplasmodial activity of dehydroabietinol, a constituent of Hyptis suaveolens.

Dehydroabietinol isolated from Hyptis suaveolens (L.) Poit. was found to inhibit growth of chloroquine-sensitive as well as chloroquine-resistant strains of Plasmodium falciparum cultivated in erythrocytes in vitro (IC 50 26-27 microM). However, erythrocytes exposed to dehydroabietinol were transformed in a dose-dependent manner towards spherostomatocytic forms with concomitant formation of endovesicles, as disclosed by transmission electron microscopy. The erythrocyte shape alterations caused by dehydroabietinol correlated well with its apparent IC 50 value. Thus, dehydroabietinol incorporates into the erythrocyte membrane, and since invasion and survival of Plasmodium parasites is known to depend on the function of the erythrocyte membrane, the observed antiplasmodial effect of dehydroabietinol is presumably an indirect effect on the host cell. Because of these findings, microscopic investigations should be generally used to support claims of antimalarial effects of apolar natural products.

Abietanes↗
PubMed2004

In vitro antimalarial activity of biflavonoids from Wikstroemia indica.

In our investigation of in vitro antimalarial screening of medicinal herbal extracts, the n-BuOH extract from the root of Wikstroemia indica showed a potent inhibitory effect. Fractionation of the active extract led to the isolation of two biflavonoids, sikokianin B ( 1) and sikokianin C ( 2) with IC (50) values 0.54 microg/mL and 0.56 microg/mL, respectively, against the chloroquine-resistant strain of Plasmodium falciparum. This is the first report of the biological activity of 1 and 2. As the structure of l has remained unsettled, we confirmed the conformation by (1)H- and (13)C-NMR.

Animals↗
PubMed2004

In vitro and in vivo antimalarial properties of isostrychnopentamine, an indolomonoterpenic alkaloid from Strychnos usambarensis.

Isostrychnopentamine (ISP) is an asymmetric indolomonoterpenic alkaloid isolated from the leaves of Strychnos usambarensis. The in vitro antiplasmodial activities against five Plasmodium falciparum cell lines were evaluated: ISP possessed an in vitro IC (50) near 0.1 microM against all P. falciparum cell lines tested (chloroquine-resistant and chloroquine-sensitive lines) and showed antiplasmodial selectivity compared to cytotoxicity on human cell lines. The stage-dependent susceptibility to a short exposure of ISP was then investigated. The ring stage was shown to be the most sensitive one, but all stages were affected by ISP treatment. By means of fluorescence microscopy, it was shown that ISP was not accumulated inside the food vacuole of the parasite. Finally, the in vivo antimalarial activities against the P. berghei NK173 and P. vinckei petteri murine strains were determined. The ED (50) in vivo was about 30 mg/kg/day by the intraperitoneal route (after 4 days treatment).

Alkaloids↗
PubMed2005

In vivo antimalarial activity of essential oils from Cymbopogon citratus and Ocimum gratissimum on mice infected with Plasmodium berghei.

The essential oils obtained by hydrodistillation from fresh leaves of Cymbopogon citratus and Ocimum gratissimum growing in Cameroon were analyzed by GC and GC/MS. The main constituents of the oil of Ocimum gratissimum were gamma-terpinene (21.9 %), beta-phellandrene (21.1 %), limonene (11.4 %) and thymol (11.2 %), while the oil of Cymbopogon citratus contained geranial (32.8 %), neral (29.0 %), myrcene (16.2 %) and beta-pinene (10.5 %). The effects of these oils on the growth of Plasmodium berghei were investigated. Both oils showed significant antimalarial activities in the four-day suppressive in vivo test in mice. At concentrations of 200, 300 and 500 mg/kg of mouse per day, the essential oil of C. citratus produced the highest activity with the respective percentages of suppression of parasitaemia: 62.1 %, 81.7 % and 86.6 %. The corresponding values for the oil of O. gratissimum at the same concentrations were 55.0 %, 75.2 % and 77.8 %, respectively. Chloroquine (10 mg/kg of mouse, positive control) had a suppressive activity of 100 %.

Animals↗
PubMed2005

Semisynthetic 15-O-acyl- and 1,15-di-O-acyleurycomanones from Eurycoma longifolia as potential antimalarials.

Among the quassinoids isolated from Eurycoma longifolia Jack, eurycomanone was identified as the most potent and toxic inhibitor of the chloroquine-resistant Gombak A isolate of Plasmodium falciparum. Several diacylated derivatives of eurycomanone, 1,15-di-O-isovaleryleurycomanone, 1,15-di-O-(3,3-dimethylacryloyl)- eurycomanone and 1,15-di-O-benzoyleurycomanone were synthesized by direct acylation with the respective acid chlorides. The monoacylated 15-O-isovaleryleurycomanone was synthesized by selective protection of the other hydroxy groups of eurycomanone with trimethylsilyl trifluoromethanesulphonate to enable the exclusive acylation of its C-15 hydroxy group. This was followed by the removal of the protecting groups with citric acid. The diacylated eurycomanones exhibited lower antiplasmodial activity against the Gombak A isolates and lower toxicity in the brine shrimp assay when compared to eurycomanone. In contrast, the monoacylated derivative displayed comparable antiplasmodial potency to eurycomanone, but its toxicity was reduced. Thus, preliminary studies of the synthesized acylated eurycomanones have shown that acylation only at the C-15 hydroxy group may be worthy of further antimalarial investigation.

Animals↗
PubMed1998

Antimalarial xanthones from Garcinia cowa.

Five xanthones from the bark of Garcinia cowa, namely 7-O-methylgarcinone E (1), cowanin (2), cowanol (3), cowaxanthone (4), and beta-mangostin (5), were found to possess in vitro antimalarial activity against Plasmodium falciparum with IC50 values ranging from 1.50 to 3.00 micrograms/ml. Complete 1H- and 13C-NMR assignments of these compounds are also reported.

Animals↗
PubMed1998

Antimalarial naphthoquinones from Nepenthes thorelii.

Roots of Nepenthes thorelii yielded plumbagin, 2-methylnaphthazarin, octadecyl caffeate, isoshinanolone, and droserone. In addition, seven derivatives were prepared from plumbagin. Each of these natural and semisynthetic compounds was evaluated for in vitro antimalarial potential.

Animals↗
PubMed1997

Betulinic acid: isolation from Triphyophyllum peltatum and Ancistrocladus heyneanus, antimalarial activity, and crystal structure of the benzyl ester.

The known lupane-type triterpene betulinic acid (3) was isolated for the first time from Triphyophyllum peltatum and Ancistrocladus heyneanus. It was found to exhibit moderate to good in vitro antimalarial activity against asexual erythrocytic stages of the human malaria parasite Plasmodium falciparum. A first X-ray structure analysis succeeded after conversion into its benzyl ester 4.

Animals↗
PubMed1997

Composition and antimalarial activity in vitro of the essential oil of Tetradenia riparia.

The essential oil from the leaves and stems of Tetradenia riparia was analysed by GC and GC/MS and 35 components were identified. The main constituents were alpha-terpineol (22.6%), fenchone (13.6%), beta-fenchyl alcohol (10.7%), beta-caryophyllene (7.9%), and perillyl alcohol (6.0%). Moderate antimalarial activities were recorded against two strains of Plasmodium falciparum.

Animals↗