Artesunate versus artemether for the treatment of recrudescent multidrug-resistant falciparum malaria.
Ric N. PriceMichèle van VugtFrançois NostenC. LuxemburgerA BrockmanL PhaipunT ChongsuphajaisiddhiNicholas J. White
78
Citation
15
Reference
10
Related Paper
Citation Trend
Abstract:
The therapeutic efficacy and toxicity of artesunate (2mg/kg/day for five days, then 1 mg/kg/day for two days: total=12 mg/kg) was compared with that of artemether (4 mg/kg followed by 2 mg/kg/day for two days, then 1 mg/kg/day for four days: total=12 mg/kg) for the treatment of recrudescent multidrug-resistant falciparum malaria in an open randomized trial in 443 patients living on the western border of Thailand. Parasite and fever clearance times were similar in both groups; within 48 hr 94% (95% confidence interval [CI]=91-96%]) of the treated patients were aparasitemic and 93% (95% CI=89-96%) were afebrile. Symptom resolution and resolution of hepatomegaly were slightly slower in the artesunate group; adjusted hazards ratio=1.5 (95% CI=1-2.0, P < 0.01) and 2.2 (95% CI=1.4-8, P=0.04), respectively. There was no significant difference in times to resolution or development of anemia or splenomegaly between treatment groups. By day 28, 3% (95% CI=0.3-5%) of the patients treated with artesunate and 6% of those treated with artemether (95% CI = 2-9%) had recurrent infections (P=0.3). Both regimens were very well tolerated, with no significant adverse effects attributable to either derivative. Overall, these data suggest that the two oral artemisinin derivatives are safe, highly effective, and result in equivalent therapeutic responses in the treatment of drug-resistant falciparum malaria.Keywords:
Artesunate
Artemether
A 5-day course of oral artesunate at total doses of 1200, 600, 650 mg and intramuscular artemether 480 mg proved effective (90-100% cured) in the treatment of multidrug resistant falciparum malaria in Thailand. Shorter courses yielded high recrudescence rates. The fever clearance and parasite clearance times were short. The side effects were mild and transient including occasional abnormal electrocardiograms and pain at the injection site. Slight reduction of neutrophil leucocytes and reticulocytes was observed. Further studies of artesunate and artemether should be carried out to find the optimum dosage regimen and to clarify the hematological effects.
Artemether
Artesunate
Intramuscular injection
Regimen
Cite
Citations (103)
Artemether
Artesunate
Artemether/lumefantrine
Severe Malaria
Cite
Citations (0)
Artesunate
Combination therapy
Cite
Citations (54)
A study on efficacy and effectiveness of artemisinin (total dose of 60 mg/kg) and artesunate (total dose of 12 mg/kg over five days) in treatment of uncomplicated malaria was conducted in highly malaria transmitted areas in Vietnam. 126 uncomplicated malaria cases finished 14 day follow-up. 100% cure rate achieved at day 14 in patients of the efficacy groups received either artemisinin or artesunate, while it was 83% and 93% in patients treated respectively with artemisinin and artesunate of the effectiveness groups. Compliance of the treatment regimens was discussed.
Artesunate
Severe Malaria
Cite
Citations (4)
Abstract Background Artemisinin derivatives have been used for malaria treatment in Vietnam since 1989. Reported malaria cases have decreased from 1,672,000 with 4,650 deaths in 1991, to 91,635 with 43 deaths in 2006. Current national guidelines recommend artemisinin-based combination therapy (ACT), although artesunate is still available as monotherapy through the private sector. Recent reports suggest that effectiveness of ACT and artesunate monotherapy has declined in western Cambodia. This study examined Plasmodium falciparum resistance patterns over 10 years in southwest Vietnam in infected patients treated with artemisinin compounds. Methods The study was conducted in two communes in Phuoc Long district, Binh Phuoc province, 100 km west of the Cambodian border. This was chosen as a likely site for emerging artemisinin resistance because of the high prevalence of P. falciparum malaria, and the length of time that artemisinin had been in use. In vivo and in vitro monitoring of P. falciparum susceptibility to anti-malarial drugs was conducted in 1998, 2001, 2004/5, and 2008/9. Patients with confirmed P. falciparum malaria received therapy with 5 or 7 days of artemisinin (1998 and 2001 respectively) or 7 days of artesunate Results In the four surveys, 270 patients were recruited and treated. The mean parasite clearance times differed between 1998, 2001 and 2004/5 (1.8, 2.3 and 2.1 days, P < 0.01) but not between 1998 and 2008/2009. The mean parasite clearance times were correlated with parasite density at day 0 (r = 0.4; P < 0.001). Treatment failure rates after PCR adjustment were 13.8%, 2.9%, 1.2%, and 0% respectively. Susceptibility of P. falciparum to artemisinin in in vitro tests was stable during the period, except for a rise in EC90 and EC99 in 2001. Conclusions This study showed stable levels of P. falciparum sensitivity to artemisinin compounds in the two sites over a ten-year period. The introduction of ACT in this area in 2003 may have protected against the development of artemisinin resistance. Adherence to the latest WHO and Vietnamese guidelines, which recommend ACT as first-line therapy in all malarious areas, and continued monitoring along the Vietnam-Cambodia border will be essential to prevent the spread of artemisinin resistance in Vietnam.
Artesunate
Combination therapy
Cite
Citations (38)
In all experimental mammals tested (rats, dogs, primates), intramuscular injections of the oil-soluble antimalarial artemisinin derivatives artemether and arteether have produced an unusual pattern of selective damage to brain stem centers predominantly involved in auditory processing and vestibular reflexes. Artesunate, the most widely used of these compounds, is a water soluble hemisuccinate derivative given parenterally either by intravenous or intramuscular injection. The neurotoxic potential of parenteral artesunate and artemether was compared in a murine model. Adult Swiss albino mice were assigned randomly to 28-day regimens of intramuscular artemether or artesunate in doses ranging from 30 to 100 mg/kg/day. At 30 mg/kg/day, no abnormalities were detected with either drug. At 50 mg/kg/day, abnormalities were observed in six of 12 artemether recipients and two of 12 artesunate recipients. These were reversible in all but one (artemether) mouse. At 100 mg/kg/day, eight of 36 artemether recipients, two of 36 artesunate recipients, and one of 18 control mice died. All but four surviving mice in the artemether group (86%) showed obvious and usually irreversible abnormalities of balance and equilibrium, whereas only four artesunate recipients (11%) exhibited abnormalities, and these were reversible in each case (P < 0.001). At this dose the relative risk (95% confidence interval) for death or disability was 5.3 (2.6-11.2) for artemether recipients. Intramuscular artemether is significantly more neurotoxic than intramuscular artesunate in this murine model.
Artemether
Artesunate
Neurotoxicity
Intramuscular injection
Cite
Citations (103)
(1) Plasmodium falciparum malaria can be fatal, especially in young children and non-immune persons. Several drugs are effective but emergence of parasite resistance limits the choice in various parts of the world. Resistance to mefloquine and even to quinine has been reported in Southeast Asia; (2) What is the role of artemisinin derivatives (mainly artesunate and artemether) in the treatment of uncomplicated P. falciparum malaria? To answer this question we conducted a review of the literature, based on Prescrire's standard methodology; (3) Trials of single-agent therapy with artemisinin derivatives showed rapid clinical and parasitological effects, but relapses were frequent during the weeks following treatment. Artemisinin derivatives are therefore used in combination with other antimalarials; (4) In 2006, no parasite resistance to artemisinin derivatives has been detected in Southeast Asia after about 10 years of use; (5) In Southeast Asia, parasitological failure at 28 days was less frequent after treatment with artesunate (for 3 days) plus mefloquine than with mefloquine alone. The artemether + lumefantrine combination has similar efficacy to the artesunate + mefloquine combination. In Africa, several trials have shown that combinations based on artemisinin derivatives are more consistently effective than combinations not including artemisinin derivatives. In regions with high-level resistance to amodiaquine, one trial showed that artemether + lumefantrine was more effective than artesunate + amodiaquine; (6) The main adverse effects of artemisinin derivatives are gastrointestinal and neurological disorders, but less are rarely severe. Combinations based on artemisinin derivatives have different adverse effects, depending on the drugs used; (7) Artesunate is the artemisinin derivative most widely studied in pregnant women: in a series of more than 400 pregnancies, abnormalities were no more frequent than in the general population; (8) In practice, in regions where P. falciparum malaria is endemic, early combination therapy based on artemisinin derivatives is often recommended. For uncomplicated malaria in travellers, combination therapy based on artemisinin derivatives is one option, along with atovaquone + proguanil, quinine (less convenient) and mefloquine (frequent neuropsychological effects).
Artesunate
Amodiaquine
Artemether
Combination therapy
Lumefantrine
Artemether/lumefantrine
Cite
Citations (0)
A monoclonal antibody (MAb) 1C1 against artemisinin was prepared by a cell fusion with splenocytes and aminopterin-sensitive myeloma cells, SP2/0. An artesunate-BSA conjugate was used as immunogen to raise antibodies specific to artemisinin. The prepared anti-artemisinin MAb-1C1 have a novel characteristic which shows a specificity to compounds that are structurally related to artemisinin such as artesunate (630 %) and dihydroartemisinin (29.9 %). By using MAb-1C1, a specific and reliable ELISA was developed for the detection of compounds structurally related to artemisinin. The system shows a full measuring range from 2 to 20 μg/mL in the case of artemisinin and from 4 to 125 ng/mL in the case of artesunate in the competitive ELISA, and was validated to be of use for surveying and breeding of Artemisia annua containing a high amount of artemisinin as well as for the characterization of the pharmacokinetics of artemisinin and its derivatives.
Artesunate
Dihydroartemisinin
Artemisia annua
Immunogen
Cite
Citations (20)
Objective To observe the antitumor effect of artemisinin and its derivatives in vitro.Methods Microculture tetrazolium assay was applied to test the cytotoxicity of artemisinin,dihydroartemisinine,artemether and artesunate to human lung cancer A549 cell line,human gastric cancer BGC823 cell line,human colon carcinoma HCT116 cell line,human erythroleukemia K562 cell line and human hepatocarcinoma SMMC7721 cell line in vitro.Results Artemisinin,dihydroartemisinine,artemether and artesunate showed selective cytotoxicity to these five tumor cell lines.Conclusion Artemisinin,dihydroartemisinine,artemether and artesunate have different antitumor activities in vitro.
Artesunate
Artemether
Microculture
Artemisia annua
K562 cells
Cite
Citations (1)
The pharmacokinetics of artemisinin (ART) and artesunate (ARTS) in healthyvolunteers [letter; comment]
Artesunate
Cite
Citations (7)