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At least 19 recordsLinked to original sources
PubMed1999

[Comparison of sensitivity of artesunate-sensitive and artesunate-resistant Plasmodium falciparum to chloroquine and amodiaquine].

AIM: To explore the in vitro sensitivity of artesunate-sensitive and -resistant Plasmodium falciparum to chloroquine and amodiaquine and to observe the effect of artesunate combined with chloroquine and artesunate combined with amodiaquine on artesunate-resistant P. falciparum. METHODS: The sensitivity of the artesunate-sensitive and -resistant P. falciparum to chloroquine and amodiaquine and their combination with artesunate was compared by using Rieckmann's in vitro micro-technique. RESULTS: The ID50 and ID95 values of chloroquine, amodiaquine and artesunete were 90.9, 50.9, 9.6 nmol/L and 320.0, 320.0, 40.0 nmol/L to the artesunate-sensitive P. falciparum respectively and were 112.0, 133.5, 85.1 nmol/L and 320.0, 320.0, 400.0 nmol/L to artesunate-resistant P. falciparum, respectively. When artesunate was combined with chloroquine, the ID50 values of the 2 drugs were 3.2 and 20.0 nmol/L to the artesunate-resistant P. falciparum. When artesunate was combined with amodiaquine, the ID95 values of the 2 drugs were 3.2 and 5.0 nmol/L to the artesunate-resistant P. falciparum, respectively. CONCLUSION: The artesunate-resistant P. falciparum has no cross resistance to chloroquine and amodiaquine, however, artesunate combined with chloroquine or amodiaquine exhibit an apparent synergistic effect in vitro.

Amodiaquine↗
PubMed2000

[Effect of pyronaridine, mefloquine and quinine on artesunate-sensitive and artesunate-resistant Plasmodium falciparum].

OBJECTIVE: To compare the sensitivity of artesunate-sensitive and artesunate-resistant P. falciparum to pyronaridine, mefloquine and quinine and to understand the effect of artesunte combined with the above-mentioned 3 drugs respectively on artesunate-resistant P. falciparum. METHODS: Rieckmann's in vitro miorotechnique was used. RESULTS: The ID50 values of pyronaride, mefloquine, quinine and artesunate were 59.0, 69.7, 283.8 and 9.6 nmol/L to artesunate-sensitive P. falciparum; the ID50 of the 4 drugs mentioned above were 170.6, 63.2, 272.4 and 85.1 nmol/L to the artesunate-resistant P. falciparum, respectively. In artesunate pyronaridine combination, the ID50 values were 1/3.7 (22.8/85.1) and 1/4.7 (36.6/170.6) of the 2 drugs singly used. In artesunate mefloquine combinaton, the ID95 is 1/125 (3.2/400) and 1/16 (80/128) of the 2 drugs singly used, respectively. CONCLUSION: The artesunate-resistant P. falciparum isolate has no cross resistance to mefloquine and quinine. When artesunate was used in combination with the 2 drugs mentioned above respectively, the efficacy proved to be enhanced.

Animals↗
PubMed2004

Developmental toxicity of artesunate and an artesunate combination in the rat and rabbit.

The artemisinins are playing an increasingly important role in treating multidrug-resistant malaria. The artemisinin, artesunate, is currently in use in Southeast Asia and is advocated for use in Africa. In these areas, more than one million people die of malaria each year, with the highest mortality occurring in children and pregnant women. To test the developmental toxicity in ICH-compliant animal studies, embryofetal development studies were conducted in rats and rabbits treated with artesunate alone or a three-drug combination (CDA) consisting of chlorproguanil hydrochloride, Dapsone, and artesunate in the ratio 1.00:1.25:2.00. Developmental toxicity seen with CDA could be attributed to the administered dose of artesunate. The hallmark effect of artesunate exposure was a dramatic induction of embryo loss, apparent as abortions in rabbits and resorptions in both rats and rabbits. In addition, low incidences of cardiovascular malformations and a syndrome of skeletal defects were induced at or close to embryolethal doses of artesunate in both rats and rabbits. The cardiovascular malformations consisted of ventricular septal and vessel defects. The skeletal syndrome consisted of shortened and/or bent long bones and scapulae, misshapen ribs, cleft sternebrae, and incompletely ossified pelvic bones. These developmental effects were observed largely in the absence of any apparent maternal toxicity. The no or low adverse effect levels were in the range of 5 to 7 mg/kg/day artesunate. Encouragingly, no adverse drug-related developmental effects have been observed in a limited number of pregnant women (more than 100 first trimester and 600 second and third trimester) treated with artemisinins, primarily artesunate. Investigations of the mechanism of developmental toxicity are ongoing to attempt to determine whether rats and rabbits are more sensitive to artemisinins than humans.

Abnormalities, Drug-Induced↗
PubMed2006

Population pharmacokinetics of artesunate and dihydroartemisinin following intra-rectal dosing of artesunate in malaria patients.

BACKGROUND: Intra-rectal artesunate has been developed as a potentially life-saving treatment of severe malaria in rural village settings where administration of parenteral antimalarial drugs is not possible. We studied the population pharmacokinetics of intra-rectal artesunate and the relationship with parasitological responses in patients with moderately severe falciparum malaria. METHODS AND FINDINGS: Adults and children in Africa and Southeast Asia with moderately severe malaria were recruited in two Phase II studies (12 adults from Southeast Asia and 11 children from Africa) with intensive sampling protocols, and three Phase III studies (44 children from Southeast Asia, and 86 children and 26 adults from Africa) with sparse sampling. All patients received 10 mg/kg artesunate as a single intra-rectal dose of suppositories. Venous blood samples were taken during a period of 24 h following dosing. Plasma artesunate and dihydroartemisinin (DHA, the main biologically active metabolite) concentrations were measured by high-performance liquid chromatography with electrochemical detection. The pharmacokinetic properties of DHA were determined using nonlinear mixed-effects modelling. Artesunate is rapidly hydrolysed in vivo to DHA, and this contributes the majority of antimalarial activity. For DHA, a one-compartment model assuming complete conversion from artesunate and first-order appearance and elimination kinetics gave the best fit to the data. The mean population estimate of apparent clearance (CL/F) was 2.64 (l/kg/h) with 66% inter-individual variability. The apparent volume of distribution (V/F) was 2.75 (l/kg) with 96% inter-individual variability. The estimated DHA population mean elimination half-life was 43 min. Gender was associated with increased mean CL/F by 1.14 (95% CI: 0.36-1.92) (l/kg/h) for a male compared with a female, and weight was positively associated with V/F. Larger V/Fs were observed for the patients requiring early rescue treatment compared with the remainder, independent of any confounders. No associations between the parasitological responses and the posterior individual estimates of V/F, CL/F, and AUC0-6h were observed. CONCLUSIONS: The pharmacokinetic properties of DHA were affected only by gender and body weight. Patients with the lowest area under the DHA concentration curve did not have slower parasite clearance, suggesting that rectal artesunate is well absorbed in most patients with moderately severe malaria. However, a number of modelling assumptions were required due to the large intra- and inter-individual variability of the DHA concentrations.

Administration, Rectal↗
PubMed1998

Comparative clinical trial of artesunate suppositories and oral artesunate in combination with mefloquine in the treatment of children with acute falciparum malaria.

A randomized pilot study to compare the safety and efficacy of artesunate suppositories (15 mg/kg/day for three days) versus oral artesunate (6 mg/kg/day for three days), both in combination with mefloquine (25 mg/kg), was conducted in 52 Thai children with uncomplicated multidrug-resistant falciparum malaria. Forty-five patients (87%) had a full 28-day follow-up in the hospital to assess efficacy and exclude reinfection. Mean [range] times to fever clearance of the two groups were similar (42 hr [15-104] versus 42 hr [6-119]). Artesunate suppositories resulted in significantly longer times to achieve 50% and 90% reductions of the initial parasite counts (17 and 26 hr versus 9 and 15 hr; P < 0.05 and P < 0.001). Time [range] to parasite clearance was longer in the artesunate suppositories group (42 hr [14-93] versus 35 hr [16-69]), but the difference was not significant. The cure rates by days 28 were not significantly different, 92% for artesunate suppository-treated patients and 100% for oral artesunate-treated patients. Both drug regimens are safe and effective. Further studies are needed to characterize the pharmacokinetic properties and the optimum regimen of artesunate suppositories for the treatment of severe malaria.

Administration, Oral↗
PubMed1998

Plasma levels of artesunate and dihydroartemisinin in children with Plasmodium falciparum malaria in Gabon after administration of 50-milligram artesunate suppositories.

A thermostable suppository of artesunate (artesunic acid) has been developed. In Gabon, 12 children with Plasmodium falciparum malaria received two administrations of this suppository in a 4-hr interval. Parasitemia and fever were then measured and the plasma levels of artesunate and its active metabolite, dihydroartemisinin, were determined by means of a reversed phase high-pressure liquid chromatography method using reductive electrochemical detection. Substantial parasite clearance (97-100%) was noted 24 hr after the beginning of the treatment and body temperature had returned to normal. Absorption, metabolism, and elimination of artesunate were rapid. Mean values of maximum plasma levels (Cmax) and maximum concentration peak times (tmax) were evaluated. The Cmax of dihydroartemisinin (0.18 +/- 0.10 microg/ml [mean +/- SE]) was higher than the Cmax of artesunate (0.09 +/- 0.04 microg/ml) and the tmax of dihydroartemisinin (1.13 +/- 0.58 hr) was higher than the tmax of artesunate (0.58 +/- 0.19 hr). Plasma levels 30 min after the second suppository administration were not consistently higher than those found 30 min after the first administration.

Absorption↗
PubMedDate not supplied

A comparison of artesunate alone with combined artesunate and quinine in the parenteral treatment of acute falciparum malaria.

In some areas clinicians have combined parenteral artesunate and quinine in the belief that the 2 drugs would be additive or synergistic in severe malaria. A randomized comparison of the effectiveness of intravenous (i.v.) artesunate versus i.v. artesunate and i.v. quinine together on parasite clearance was conducted in 1998/99 amongst 69 patients with uncomplicated and severe Plasmodium falciparum malaria in western Thailand. The parasite clearance time did not differ significantly between the 2 treatment groups (P = 0.12), but adverse events were significantly more frequent in the artesunate plus quinine group (P = 0.05). Quinine did not have a significant antipyretic effect and artesunate did not affect the electrocardiographic QTc interval. There is no benefit evident from combining parenteral administration of these 2 antimalarial drugs in the acute phase of treatment.

Acute Disease↗
PubMed2003

Randomised efficacy and safety study of two 3-day artesunate rectal capsule/mefloquine regimens versus artesunate alone for uncomplicated malaria in Ecuadorian children.

The combination of artesunate and mefloquine is one of the most effective treatments against multidrug-resistant falciparum malaria. Experience in children is however limited. The objective of this study was to compare the efficacy and safety of two artesunate/mefloquine combinations with artesunate monotherapy in Ecuadorian children. A total of 150 children with an age between 2 and 12 years, confirmed to have uncomplicated falciparum malaria, were randomly selected and divided in three treatment groups of 50 patients each. Group 1 received 50 mg rectal capsules alone (40 mg/kg total dose) administered over 6 days. Group 2 received 50 mg rectal capsules (30 mg/kg total dose) for 3 days combined with mefloquine (20 mg/kg total dose) on day 1. Group 3 was treated with 50 mg rectal capsules (30 mg/kg total dose) for 3 days, combined with mefloquine on days 1 and 3 (15-17 mg/kg total dose). Patients were continuously followed up and controlled by clinical and laboratory examinations for 7 days as well as on days 14, 21 and 28. An additional parasite examination was performed at 2 months following therapy. Clearance of parasitaemia was comparable between treatment groups. These were 9.2, 9.2 and 8.3 h for Groups 1, 2 and 3, respectively. Cure rates at day 28 were 76, 96 and 94% and after 2 months 60, 88 and 80%, respectively. There were no adverse events (AEs) reported during the study. Vital signs and laboratory examinations revealed no changes of clinical relevance. It can be concluded that the combination of artesunate rectal capsules with mefloquine is effective and safe. Starting concomitant administration already on day 1 is well tolerated. This combination significantly reduces the incidence of recrudescence compared to artesunate monotherapy. Comparing the two tested artesunate/mefloquine regimens, a total mefloquine dose of 20 mg/kg seems to be more effective compared to a total dose of 15-17 mg/kg. Further studies seem to be warranted.

Administration, Rectal↗
PubMed2000

Effects of artesunate, dihydroartemisinin, and an artesunate-dihydroartemisinin combination against Toxoplasma gondii.

The effect of artesunate and its metabolite dihydroartemisinin against the cerebral cysts of Toxoplasma gondii was studied. In vitro experiments were performed with the THP-1 cell line and showed an inhibition of parasite growth of approximately 70% with 0.1-0.5 microg/ml of dihydroartemisinin for 96 hr. However, with artesunate, dihydroartemisinin, or a combination (50:50) of them, the number of tachyzoites decreased approximately 40-50% and they appeared motionless. Fifty-eight to 72 hr after washing of the tachyzoites and THP-1 cells in culture, parasitized cells reappeared. In vivo, the 50:50 artesunate-dihydroartemisinin combination produced a decrease in cerebral cysts of approximately 40% after only 5 days of treatment. However, transplantations into naive mice using brains of treated mice gave positive results.

Animals↗
PubMed2005

Malaria in the Nuba Mountains of Sudan: baseline genotypic resistance and efficacy of the artesunate plus sulfadoxine-pyrimethamine and artesunate plus amodiaquine combinations.

Both northern and southern Sudan are deploying artemisinin-based combinations against uncomplicated Plasmodium falciparum malaria (artesunate+sulfadoxine-pyrimethamine [AS+SP] in the north, artesunate+amodiaquine [AS+AQ] in the south). In 2003, we tested the efficacy of 3 day AS+SP and AS+AQ regimens in vivo in the isolated, seasonally endemic Nuba Mountains region (the first study of AS combinations in southern Sudan). We also analysed pre-treatment blood samples for mutations at the P. falciparum chloroquine transporter (Pfcrt) gene (associated with CQ resistance), and at the dihydrofolate reductase (Dhfr) gene (associated with pyrimethamine resistance). Among 161 randomized children under 5 years, PCR-corrected cure rates after 28 days were 91.2% (52/57, 95% CI 80.7-97.1) for AS+SP and 92.7% (51/55, 95% CI 82.4-98.0) for AS+AQ, with equally rapid parasite and fever clearance. The Pfcrt K76T mutation occurred in 90.0% (144/160) of infections, suggesting CQ would work poorly in this region. Overall, 82.5% (132/160) carried mutations at Dhfr (N51I, C59R or S108N, but not I164L), but triple mutants (more predictive of in vivo SP failure) were rare (3.1%). CQ use should be rapidly discontinued in this region. SP resistance may propagate rapidly, and AS+AQ is likely to be a better long-term option, provided AQ use is limited to the combination.

Amodiaquine↗
PubMed2005

Antimalarial efficacy of chloroquine, amodiaquine, sulfadoxine-pyrimethamine, and the combinations of amodiaquine + artesunate and sulfadoxine-pyrimethamine + artesunate in Huambo and Bie provinces, central Angola.

We studied three antimalarial treatments in Caala and Kuito, Angola, in 2002 and 2003. We tested chloroquine (CQ), amodiaquine (AQ) and sulfadoxine-pyrimethamine (SP) in Caala, and AQ, SP and the combinations AQ+artesunate (AQ+AS) and SP+artesunate (SP+AS) in Kuito. A total of 619 children (240 in Caala, 379 in Kuito) with uncomplicated Plasmodium falciparum malaria were followed-up for 28 days, with PCR genotyping to distinguish recrudescence from reinfection. PCR-corrected failure proportions at day 28 were very high in the CQ group (83.5%, 95% CI 74.1-90.5), high in the SP groups (Caala: 25.3%, 95% CI 16.7-35.8; Kuito: 38.8%, 95% CI 28.4-50.0), around 20% in the AQ groups (Caala: 17.3%, 95% CI 10.0-27.2; Kuito: 21.6%, 95% CI 14.3-30.6) and very low in the artemisinin-based combination groups (1.2%, 95% CI 0.0-6.4 for each combination AQ+AS and SP+AS). These results show that CQ and SP are no longer efficacious in Caala and Kuito and that the moderate efficacy of AQ is likely to be compromised in the short term if used as monotherapy. We recommend the use of AQ with AS, though this combination might not have a long useful therapeutic life because of AQ resistance.

Amodiaquine↗
PubMed2006

Artesunate + amodiaquine and artesunate + sulphadoxine-pyrimethamine for treatment of uncomplicated malaria in Democratic Republic of Congo: a clinical trial with determination of sulphadoxine and pyrimethamine-resistant haplotypes.

We undertook a trial of artesunate + amodiaquine (AS + AQ) and artesunate + sulphadoxine-pyrimethamine (AS + SP) in 180 children of age 6-59 months with uncomplicated malaria in Democratic Republic of Congo. Children were randomly allocated to receive 3 days observed treatment of AS + AQ (n = 90) or 3 days of AS + SP (n = 90). Primary efficacy outcomes were 28-day parasite recurrence rates, and recrudescence rates were adjusted by genotyping to distinguish new infection and recrudescence. In addition, we determined the prevalence of molecular markers of resistance to sulphadoxine and pyrimethamine. Day 28 parasite recurrence rates were 16.9% (14/83; 95% CI: 9.5-26.7) in the AS + AQ group and 34.6% (28/81; 95% CI: 24.3-46.0) in the AS + SP group (P = 0.009). After PCR correction, recrudescence rates were 6.7% (5/74; 95% CI: 2.2-15.1) for AS + AQ and 19.7% (13/66; 95% CI: 10.9-31.3) for AS + SP (P = 0.02). There was no significant difference between the two arms in time to parasite clearance, fever clearance and gametocyte clearance. Parasite genotyping showed high frequencies of dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) molecular SP-resistance markers, with 57% of the samples showing more than three mutations linked to SP resistance, and 27% with triple-dhfr/double-dhps haplotype, confirming that SP treatment failure rates are likely to be high. AS + AQ had significantly higher efficacy than AS + SP. These results contributed to the subsequent change to AS + AQ as first-line regimen in the country. Efforts to properly implement the new protocol and maintain adherence at acceptable levels should include health staff and patient sensitization. The 6.8% recrudescence rate indicates that AS + AQ should be monitored closely until a more effective artemisinin combination therapy regimen is needed and can be introduced.

Amodiaquine↗
PubMed2004

Disposition of artesunate and dihydroartemisinin after administration of artesunate suppositories in children from Papua New Guinea with uncomplicated malaria.

A detailed pharmacokinetic analysis was performed with 47 children from Papua New Guinea with uncomplicated falciparum or vivax malaria treated with artesunate (ARTS) suppositories (Rectocaps) given in two doses of approximately 13 mg/kg of body weight 12 h apart. Following an intensive sampling protocol, samples were assayed for ARTS and its primary active metabolite, dihydroartemisinin (DHA), by liquid chromatography-mass spectrometry. A population pharmacokinetic model was developed to describe the data. Following administration of the first dose, the mean maximal concentrations of ARTS and DHA were 1,085 nmol/liter at 0.9 h and 2,525 nmol/liter at 2.3 h, respectively. The absorption half-life for ARTS was 2.3 h, and the conversion half-life (ARTS to DHA) was 0.27 h, while the elimination half-life of DHA was 0.71 h. The mean common volumes of distribution for ARTS and DHA relative to bioavailability were 42.8 and 2.04 liters/kg, respectively, and the mean clearance values relative to bioavailability were 6 and 2.2 liters/h/kg for ARTS and DHA, respectively. Substantial interpatient variability was observed, and the bioavailability of the second dose relative to that of the first was estimated to be 0.72. The covariates age, sex, and alpha-thalassemia genotype were not influential in the pharmacokinetic model development; but the inclusion of weight as a covariate significantly improved the performance of the model. An ARTS suppositories dose of 10 of 20 mg/kg is appropriate for use in children with uncomplicated malaria.

Aging↗
PubMed1998

Influence of blister packaging on the efficacy of artesunate + mefloquine over artesunate alone in community-based treatment of non-severe falciparum malaria in Myanmar.

Three studies were carried out to determine the need, acceptability, and efficacy of adding mefloquine to artemisinin derivatives (AD) for the first-line treatment of uncomplicated falciparum malaria. The first was a retrospective study of 255 basic health workers which showed that their recommendation of AD to patients depended on their level of training. None of the paramedics/midwives and only 9% of 129 doctors had prescribed AD, and no one had recommended AD in combination with mefloquine; 72% of patients used courses that were too short for parasitological cure. To promote the addition of mefloquine to AD regimens we conducted intervention workshops with health care providers and subsidized the cost of mefloquine to patients. In the second study, we interviewed 200 patients before and after the intervention to evaluate drug compliance with full doses of AD and use of subsidized mefloquine. After the intervention, we found that only 3.6% had used mefloquine and 62% had taken non-curative doses of AD. In the third study, we provided blister packs of medication in daily doses and compared the intake of AD + placebo (158 patients) with that of AD + mefloquine (222 patients) for 5 days. The compliance with both regimens was 99%. Blood smears for parasites on day 28 showed one positive in the AD + mefloquine group and 7 positive in the AD group. We conclude that provision of blister packs of daily doses is a very effective way to improve compliance with short courses and drug combinations, but the efficacy of the combination in Myanmar in this particular study was only marginally higher than that of AD alone.

Adolescent↗
PubMed2000

A colorimetric field method to assess the authenticity of drugs sold as the antimalarial artesunate.

Artesunate is the most widely used of the artemisinin derivatives. These drugs are being used increasingly throughout the tropical world, and are an essential component of the treatment of multi-drug resistant malaria. The recent and widespread appearance of counterfeit artesunate tablets in several countries in Southeast Asia poses a serious threat to health in this region. We have developed a simple, inexpensive colorimetric test to determine artesunate authenticity in tablets. The test is based on a reaction between an alkali decomposition product of artesunate and a diazonium salt, fast red TR (FRTR). The appearance of a yellow color indicates the presence of artesunate. The specificity of the test is dependent on the pH of the reaction. Among other antimalarials tested, (i.e. artemisinin, artemether, chloroquine, quinine, primaquine, sulfadoxine, and pyrimethamine) only artesunate produced a positive color reaction at pH 4. The assay requires only 1% of the total weight of a standard tablet containing 50 mg of artesunate and can be completed within 10 min. The method was tested on six genuine artesunate tablets and six counterfeit artesunate tablets obtained in Southeast Asia. The average amount of artesunate in the genuine tablets was determined to be 50.8 +/- 2.9 mg while the counterfeit tablets were found to contain no artesunate.

Antimalarials↗
PubMed1996

Chemical stability of artesunate injection and proposal for its administration by intravenous infusion.

Artesunate, the only artemisinin analogue that can be given intravenously, produces rapid parasite and fever clearance in falciparum malaria. A significant therapeutic problem is a high, late recrudescence rate, probably due to short half-lives of both artesunate and its active metabolite dihydroartemisinin relative to conventional dosing intervals. One method of extending the duration of action of artesunate could be to administer the drug by infusion rather than bolus injection, provided that it is chemically stable at ambient temperature. Artesunate was found to be stable in 0.9% w/v sodium chloride at 9 degrees C, 23 degrees C and 36.5 degrees C for 130, 10.6 and 1.6 h, respectively. Interpolating from an Arrhenius plot, artesunate should be stable for approximately 4 h at 30 degrees C, a temperature representative of ambient conditions in tropical countries. Exposure to light did not affect the degradation rate. Single compartment pharmacokinetic modelling was used to evaluate potential differences in artesunate and dihydroartemisinin plasma concentrations following administration of artesunate by intravenous bolus or infusion. A bolus injection of artesunate at a dose of 4 mg kg-1 gives a peak concentration of 5.3 mg L-1, falling to 0.005 mg L-1 at 5 h. The same dose infused over 4 h results in a peak concentration of 0.92 mg L-1, falling to 0.005 mg L-1 at 8 h. Simultaneous modelling of dihydroartemisinin showed that while its peak plasma concentration was reduced by 27% and the peak delayed by 2.5 h following artesunate administration by infusion, substantially higher concentrations were maintained compared with those predicted after bolus artesunate. These data indicate that artesunate can be administered as a high-dose intravenous infusion, thus avoiding high plasma concentrations. This strategy also has the potential to prolong the duration of antimalarial effect and reduce toxicity, and consequently improve clinical outcome in seriously ill patients.

Antimalarials↗
PubMed1995

Artesunate. A review of its pharmacology and therapeutic efficacy in the treatment of malaria.

Artesunate is an antimalarial agent, available in oral, rectal and parenteral formulations, that provides a rapid clinical effect in patients with Plasmodium falciparum malaria. The rapidity of effect, availability of an intravenous and intramuscular formulation and convenient dosage regimen make artesunate an ideal candidate for the treatment of severe malaria, including cerebral disease. While some results have been promising, there is no clear evidence to date that artesunate reduces mortality in patients with cerebral malaria to any greater extent than standard quinine therapy. When given as monotherapy, treatment should be continued for at least 5 to 7 days to prevent recrudescence. Combination therapy with mefloquine allows artesunate to be administered over 3 days or less, with a satisfactory clinical outcome maintained. Although optimal dosages remain to be determined, this combination continues to provide the rapid onset of clinical effect observed with artesunate monotherapy, but decreases the rate of recrudescence to 2% (i.e. radical cure rate of 98%) when used as treatment in patients with uncomplicated malaria from areas with a high risk of multidrug-resistance falciparum malaria. Although assessment of tolerability is complicated by the difficulty of distinguishing between disease- and treatment-related events, artesunate and artesunate-mefloquine combinations appear to be well tolerated in adults and children. Indeed, it is possible that prior administration of artesunate may reduce the incidence of mefloquine-induced vomiting. Clinical findings to date have not revealed any pattern of resistance to artesunate after use of the drug. However, given the history of the development of resistance to other antimalarial drugs, the use of artesunate should be restricted to areas of multidrug resistance, the drug should be used in combination with a longer acting agent such as mefloquine, and it should be used in regimens that provide radical cure rates of 90 to 100%. If used according to these treatment principles, artesunate will provide a well tolerated and valuable addition to the current extremely limited treatment options for multidrug-resistant falciparum malaria, a widespread parasitic disease associated with considerable mortality.

Antimalarials↗
PubMed2005

Evaluation of the anthelmintic effects of artesunate against experimental Schistosoma mansoni infection in mice using different treatment protocols.

The therapeutic effects of artesunate against experimental Schistosoma mansoni infection in mice were analyzed. Previous studies showed that artesunate is highly effective against S. japonicum infection, but the action of this drug against S. mansoni remained uncovered. The present study examines the optical conditions for artesunate against S. mansoni and evaluates the effects of inhibiting the sexual maturation of adult worms. Mice infected with S. mansoni were orally administered with artesunate according to different schedules. Four consecutive administrations of 300 mg/kg of artesunate at 2-week intervals conferred almost total protection without the development of pathological lesions in the liver. The significant reduction in the number of eggs produced by surviving worms and the status of egg maturation suggested that artesunate inhibits sexual maturation. Electron microscopy revealed that artesunate caused morphological damage, especially on the worm tegument. Artesunate was also very effective in iron-deficient mice. Furthermore, the efficacy of artesunate was equal to or better than that of artemether against S. japonicum infection. Considering that artemether is more toxic, artesunate is currently one of the most efficient drugs against immature S. mansoni.

Anemia, Iron-Deficiency↗