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. 2000;1999(2):CD000256.
doi: 10.1002/14651858.CD000256.

Artemisinin derivatives for treating uncomplicated malaria

H M McIntosh  1 , P Olliaro
Affiliations

Artemisinin derivatives for treating uncomplicated malaria

H M McIntosh et al. Cochrane Database Syst Rev. 2000.

Abstract

Background: Artemisinin derivatives are a relatively new group of drugs with antimalarial properties. As resistance to other antimalarial drugs continues to increase, artemisinin drugs may be useful alternatives.

Objectives: The objective of this review was to assess the effects of artemisinin drugs for treating uncomplicated falciparum malaria.

Search strategy: We searched the Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, Medline, Embase, Science Citation Index, Lilacs, African Index Medicus; conference abstracts and reference lists of relevant articles. We contacted organisations, researchers in the field and drug companies.

Selection criteria: Randomised and quasi-randomised trials of artemisinin derivatives, alone or in combination with other antimalarials, compared with standard antimalarial treatments, in adults or children with uncomplicated falciparum malaria. Only trials where treatment was given by mouth or suppository were included. Comparisons between different artemisinin derivatives and treatment regimens were also included.

Data collection and analysis: Eligibility and trial quality were assessed and data were extracted independently by the two reviewers.

Main results: Forty-one trials involving over 5000 patients were included. Variation in study design and quality made synthesis of the data problematic. Allocation concealment was adequate in only two trials. Most data were from areas of multidrug resistant falciparum malaria in South East Asia. Compared with standard antimalarial treatments, artemisinin drugs showed fast parasite clearance and high cure rates at follow-up, provided the duration of treatment with artemisinin drugs was adequate. Combination with mefloquine improved sustained parasite clearance and was effective in multidrug resistant areas. When doses were adequate, the combination shortened the duration of treatment. We found no evidence that artemisinin drugs are more harmful than standard treatment drugs over a typical trial period of 28 days.

Reviewer's conclusions: The evidence suggests that artemisinin drugs are effective and safe for treating uncomplicated malaria. There is no evidence from randomised trials that one artemisinin derivative is better than the others. In areas where there is mefloquine resistance, combination therapy with an artemisinin derivative appears to improve sustained parasite clearance compared with either drug alone.

PubMed Disclaimer

Conflict of interest statement

We certify that we have no affiliations with or involvement in any organisation or entity with a direct financial interest in the subject matter of the review (e.g. employment, consultancy, stock ownership, honoraria, expert testimony).

Figures

1.1
1.1. Analysis
Comparison 1 Single drug, Outcome 1 Parasite clearance at day 7.
1.2
1.2. Analysis
Comparison 1 Single drug, Outcome 2 Parasite clearance at day 28.
1.3
1.3. Analysis
Comparison 1 Single drug, Outcome 3 Adverse events (artemisinin drug vs mefloquine).
2.1
2.1. Analysis
Comparison 2 Co‐artemether vs standard treatment, Outcome 1 Parasite clearance at day 4 or day 7.
2.2
2.2. Analysis
Comparison 2 Co‐artemether vs standard treatment, Outcome 2 Parasite clearance at day 14/15.
3.1
3.1. Analysis
Comparison 3 Combination with mefloquine vs mefloquine alone, Outcome 1 Parasite clearance at day 7.
3.2
3.2. Analysis
Comparison 3 Combination with mefloquine vs mefloquine alone, Outcome 2 Parasite clearance at day 28.
3.3
3.3. Analysis
Comparison 3 Combination with mefloquine vs mefloquine alone, Outcome 3 Parasite clearance time.
3.4
3.4. Analysis
Comparison 3 Combination with mefloquine vs mefloquine alone, Outcome 4 Fever clearance time.
3.5
3.5. Analysis
Comparison 3 Combination with mefloquine vs mefloquine alone, Outcome 5 Adverse events.
4.1
4.1. Analysis
Comparison 4 Combination with mefloquine vs artemisinin drug alone, Outcome 1 Parasite clearance at day 28.
4.2
4.2. Analysis
Comparison 4 Combination with mefloquine vs artemisinin drug alone, Outcome 2 Parasite clearance time.
4.3
4.3. Analysis
Comparison 4 Combination with mefloquine vs artemisinin drug alone, Outcome 3 Time to 50/90% parasite clearance.
4.4
4.4. Analysis
Comparison 4 Combination with mefloquine vs artemisinin drug alone, Outcome 4 Fever clearance time.
4.5
4.5. Analysis
Comparison 4 Combination with mefloquine vs artemisinin drug alone, Outcome 5 Adverse events.
5.1
5.1. Analysis
Comparison 5 Combination with mefloquine: mefloquine dose/schedule, Outcome 1 Parasite clearance at day 28.
6.1
6.1. Analysis
Comparison 6 Combination with sulfadoxine‐pyrimethamine vs artemisinin drug alone, Outcome 1 Parasite clearance at day 28.
7.1
7.1. Analysis
Comparison 7 Comparison between artemisinin drugs, Outcome 1 Parasite clearance at day 7.
7.2
7.2. Analysis
Comparison 7 Comparison between artemisinin drugs, Outcome 2 Parasite clearance at day 28.
7.3
7.3. Analysis
Comparison 7 Comparison between artemisinin drugs, Outcome 3 Parasite clearance time.
7.4
7.4. Analysis
Comparison 7 Comparison between artemisinin drugs, Outcome 4 Fever clearance time.
See this image and copyright information in PMC

References

References to studies included in this review

AlinTAZ94 {published data only}
    1. Alin MH, Ashton M, Kihamia CM, Mtey GJB, Bjorkman A. Clinical efficacy and pharmacokinetics of artemisinin monotherapy and in combination with mefloquine in patients with falciparum malaria. J Clin Pharmacol 1996;41:587‐92. - PMC - PubMed
AlinTAZ96 {published data only}
    1. Alin MH, Ashton M, Kihamia CM, Mtey GJB, Bjorkman A. Multiple dose pharmacokinetics of oral artemisinin and comparison of its efficacy with that of oral artesunate in falciparum malaria patients. Trans R Soc Trop Med Hyg 1996;90(1):61‐5. - PubMed
ArnoldVNM89 {published data only}
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BunnagTHI89a {published data only}
    1. Bunnag D, Viravan C, Looareesuwan S, Karbwang J, Harinasuta T. Clinical trial of artesunate and artemether on multidrug resistant falciparum malaria in Thailand. A preliminary report. Southeast Asian J Trop Med Public Health 1991;22(3):380‐5. - PubMed
BunnagTHI89b {published data only}
    1. Bunnag D, Viravan C, Looareesuwan S, Karbwang J, Harinasuta T. Double blind randomised clinical trial of oral artesunate at once or twice daily dose in falciparum malaria. Southeast Asian J Trop Med Public Health 1991;2(4):539‐43. - PubMed
BunnagTHI92‐4a {published data only}
    1. Bunnag D, Kanda T, Karbwang J, Thimasarn K, Pungpak S, Harinasuta T. Artemether‐mefloquine combination in multidrug resistant falciparum malaria. Trans R Soc Trop Med Hyg 1995;89(2):213‐5. - PubMed
BunnagTHI92‐4b {published data only}
    1. Bunnag D, Kanda T, Krabwang J, Thimasarn K, Pungpak S, Harinasuta T. Artemether or artesunate followed by mefloquine as a possible treatment for multi drug resistant falciparum malaria. Trans R Soc Trop Med Hyg 1996;90(4):415‐17. - PubMed
CardosoBRZ93‐4 {published data only}
    1. Cardoso B da S, Dourado HV, Pinheiro M da C, et al. [An efficacy and tolerance study of oral artesunate alone and in combination with mefloquine in the treatment of uncomplicated falciparum malaria in an endemic area of Para, Brazil]. [Portuguese]. Rev Soc Bras Med Trop 1996;29(3):251‐7. - PubMed
EzedinachiNIG92 {published data only}
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GuoCHI87 {published data only}
    1. Guo XB, Fu YX, Chen PJ, et al. A randomised comparative study on the treatment of falciparum malaria with artesunate tablets and piperaquine. Clinical trial on qinghaosu and its derivatives [Chinese]. Sanya Tropical Medicine Institute 1990;1:39‐42.
    1. Guo XB, Fu YX, Chen PQ, et al. A randomised comparative study on the treatment of falciparum malaria with artesunate tablets and piperaquine. Clinical trials on Qinghaosu and its derivatives [English translation] 72‐77.
HatzTAZ(98) {published data only}
    1. Hatz C, Abdulla S, Mull R, Schellenberg D, Gathmann I, Kibatala P, et al. Efficacy and safety of CGP 56697 (artemether and benflumetol) compared with chloroquine to treat acute falciparum malaria in Tanzanian children aged 1‐5 years. Trop Med Int Health 1998;3(6):498‐504. - PubMed
    1. Hatz C, Abdulla S, Schellenberg D, Mull R, Gathmann I, Royce C. Efficacy and safety of CGP 56697 vs. chloroquine in the treatment of P falciparum malaria in children. National Institute for Medical Research 15th Annual joint scientific conference. Dar es Salaam, Tanzania, February 1997:Abstract.
    1. Irion A, Abdullah S, Felger I, Beck HP, Mull R, Hatz C. A comparative trial of CGP 56697 and chloroquine in Tanzanian children with subsequent PCR analysis of recurring parasites. Fifth International Conference on Travel Medicine: Program and Abstracts. Geneva, March 24‐27 1997:Abstract 107.
    1. Irion A, Abdullah S, Felger I, Mull R, Hatz C, Beck HP. A comparative trial of CGP 56697 and chloroquine in Tanzanian children with subsequent PCR analysis of recurring parasites. British Society for Parasitology 9th malaria meeting. Liverpool, September 1997:Abstract 4.11.
    1. Irion A, Felger I, Abdulla S, Smith T, Mull R, Tanner M, et al. Distinction of recrudescences from new infections by PCR‐RFLP analysis in a comparative trial of CGP 56697 and chloroquine in Tanzanian children. Trop Med Int Health 1998;3(6):490‐97. - PubMed
HienVNM(94)[1] {published data only}
    1. Hien TT, Arnold K, Hung NT, Loc PP, Dung NT, Cuong BM, et al. Single dose artemisinin‐mefloquine treatment for acute uncomplicated falciparum malaria. Trans R Soc Trop Med Hyg 1994;88:688‐91. - PubMed
HienVNM90 {published data only}
    1. Hien TT, Tam DTH, Cuc NTK, Arnold K. Comparative effectiveness of artemisinin suppositories and oral quinine in children with acute falciparum malaria. Trans R Soc Trop Med Hyg 1991;85:210‐1. - PubMed
HungVNM93‐4 {published data only}
    1. Hung LN, Vries PJ, Diem LT, et al. Single dose artemisinin‐mefloquine versus mefloquine alone for uncomplicated falciparum malaria. Trans R Soc Trop Med Hyg 1997;91:191‐4. - PubMed
KarbwangTHI91 {published data only}
    1. Karbwang J, Bangchang K, Thanavibul A, Bunnag D, Chongsuphajaisiddhi T, Harinasuta T. Comparison of oral artemether and mefloquine in acute uncomplicated falciparum malaria. Lancet 1992;340(8830):1245‐8. - PubMed
KarbwangTHI92a {published data only}
    1. Karbwang J, Na Bangchang K, Thanavibul A, Back DJ, Bunnag D, Harinasuta T. Pharmacokinetics of mefloquine alone or in combination with artesunate. Bull WHO 1994;72(1):83‐7. - PMC - PubMed
KarbwangTHI92b {published data only}
    1. Karbwang J, Na‐Bangchang K, Thanavibul A, et al. Comparison of oral artesunate and quinine plus tetracycline in acute complicated malaria. Bull WHO 1994;72(2):233‐8. - PMC - PubMed
KarbwangTHI92c {published data only}
    1. Karbwang J, Nabangchang K, Thanavibul A, Dittain M, Bunnag D, Hrinasuta T. Comparative clinical trial of artesunate and the combination of artesunate‐mefloquine in multidrug resistant falciparum malaria. Clin Drug Investig 1996;11(2):84‐9.
KarbwangTHI93 {published data only}
    1. Karbwang J, Na‐Bangchang K, Thanavibul A, Laothavorn P, Ditta‐in M, Harinasuta T. A comparative clinical trail of artemether and the sequential regimen of artemether‐mefloquine in multidrug resistant falciparum malaria. J Antimicrob Chemother 1995;36:1079‐83. - PubMed
KarbwangTHI93‐4 {published data only}
    1. Karbwang J, Na‐Bangchang K, Thanavibul A, Ditta‐in M, Harinasuta T. A comparative clinical trial of two different regimens of artemether plus mefloquine in multidrug resistant falciparum malaria. Trans R Soc Trop Med Hyg 1995;89(3):296‐8. - PubMed
Li CHI82‐4 {published data only}
    1. Li GQ, Arnold K, Guo XB, Jian HX, Fu LC. Randomised comparative study of mefloquine, qinghaosu, and pyrimethamine‐sulfadoxine in patients with falciparum malaria. Lancet 1984;2(8416):1360‐1. - PubMed
LooareesuwanTHI91 {published data only}
    1. Looareesuwan S, Viravan C, Vanijanonta S, et al. Randomised trial of artesunate and mefloquine alone and in sequence for acute uncomplicated falciparum malaria. Lancet 1992;339(8797):821‐4. - PubMed
LooareesuwanTHI92b {published data only}
    1. Looareesuwan S, Wilairatana P, Viravan C, Vanijanonta S, Pitisuttithum P, Kyle DE. Open randomised trial of oral artemether alone and a sequential combination with mefloquine for acute uncomplicated malaria. Am J Trop Med Hyg 1997;56(6):613‐7. - PubMed
LooareesuwanTHI93 {published data only}
    1. Looareesuwan S, Vanijanonta S, Viravan C, Wilairatana P, Charoenlarp P, Andrial M. Randomized trial of mefloquine alone and artesunate followed by mefloquine for the treatment of acute uncomplicated falciparum malaria. Ann Trop Med Parasitol 1994;88(2):131‐6. - PubMed
LooareesuwanTHI95 {published data only}
    1. Looareesuwan S, Wilairatana P, Vanijanonta S, Pitisuttithum P, Ratanapong Y, Andrial M. Monotherapy with sodium artesunate for uncomplicated falciparum malaria: a comparison of 5‐day and 7‐day regimens. Acta Tropica 1997;67:197‐205. - PubMed
LuxemburgerTHI‐MYA91 {published data only}
    1. Luxemburger C, ter Kuile FO, Nosten F, et al. Single day mefloquine‐artesunate combination in the treatment of multi‐drug resistant falciparum malaria. Trans R Soc Trop Med Hyg 1994;88(2):213‐7. - PubMed
Nosten[1]THI‐MYA92‐3 {published data only}
    1. Nosten F, Luxemburger C, ter Kuile FO, et al. Treatment of multidrug‐resistant Plasmodium falciparum malaria with 3‐day artesunate‐mefloquine combination (study 1). J Infect Dis 1994;170(4):971‐7. - PubMed
Nosten[2]THI‐MYA92‐3 {published data only}
    1. Nosten F, Luxemburger C, ter Kuile FO, et al. Treatment of multidrug‐resistant Plasmodium falciparum malaria with 3‐day artesunate‐mefloquine combination (study 2). J Infect Dis 1994;170(4):971‐7. - PubMed
PriceTHI‐MYA93‐4 {published data only}
    1. Price RN, Nosten F, Luxemburger C, et al. Artesunate versus artemether in combination with mefloquine for the treatment of multidrug‐resistant falciparum malaria. Trans R Soc Trop Med Hyg 1995;89(5):523‐7. - PubMed
RugemalilaTAZ(97) {published and unpublished data}
    1. Rugemalila JB, Msangeni HA. Clinical trial of B‐artemether for the treatment of malaria in Tanzania. Unpublished manuscript.
    1. Rugemalila JB, Msangeni HA, Akida JA, et al. A randomised double blind clinical trial comparing oral B‐artemether and chloroquine for the treatment of uncomplicated malaria in Tanzania. National Institute for Medical Research 15th annual joint scientific conference Programme and abstracts. Dar es Salaam Tanzania, Abstract 22.
ThanMYA90‐91 {unpublished data only}
    1. Than M. Unpublished data obtained from the investigator, Defence Services General Hospital, Myanmar.
ThanMYA91 {unpublished data only}
    1. Than M. Unpublished data obtained from the investigator, Defence Services General Hospital, Myanmar.
ThanMYA93a {unpublished data only}
    1. Marlar Than, Ma Sabai, Khaing Khaing Gyi, Aye Yu Soe, Khin Mg Aye, Kyaw Win. Trial of oral artemisinin (Lactab) alone and in combination with mefloquine in uncomplicated falciparum malaria. Second Myanmar Health Research Congress. Vol. Abstracts:29.
    1. Than M. Unpublished data obtained from the investigator, Defence Services General Hospital, Myanmar.
ThanMYA93b {unpublished data only}
    1. Than M. Unpublished data obtained from the investigator, Defence Services General Hospital, Myanmar.
ThanMYA93c {unpublished data only}
    1. Marlar Than, Ma Sabai, Khaing Khaing Gyi, Aye Yu Soe, Khin Mg Aye, Kyaw Win. Different dosage regimens of oral artemether in uncomplicated falciparum malaria. Second Myanmar Health Research Congress [Abstracts]. 25.
    1. Than M. Unpublished data obtained from the investigator, Defence Services General Hospital, Myanmar.
ThanMYA94a {unpublished data only}
    1. Than M. Unpublished data obtained from the investigator, Defence Services General Hospital, Myanmar.
ThanMYA96a {unpublished data only}
    1. Than M. Unpublished data obtained from the investigator, Defence Services General Hospital, Myanmar.
ThanMYA97 {unpublished data only}
    1. Than M. Unpublished data obtained from the investigator, Defence Services General Hospital, Myanmar.
ThimasarnTHI93‐4 {published data only}
    1. Thimasarn K, Sirichaisinthop J, Chanyakhun P, et al. A comparative study of artesunate and artemether in combination with mefloquine on multidrug resistant falciparum malaria in Eastern Thailand. S East Asia J Trop Med Pub Health 1997;28(3):465‐71. - PubMed
vonSeidleinGAM96 {published data only}
    1. A randomized controlled trial of artemether/benflumetol, a new antimalarial and pyrimethamine/sulfadoxine in the treatment of uncomplicated falciparum malaria. Am J Trop Med Hyg 1998;58(5):638‐44. - PubMed
WinMYA94‐5 {published data only}
    1. Win Kyaw, Marlar Than, Ye Thwe, et al. Efficacy of artemether and artesunate suppositories (Rectocaps) in the treatment of uncomplicated falciparum malaria. Jpn J Trop Med Hyg 1996;24(suppl 1):55‐8.

References to studies excluded from this review

Alin TAZ 93 {published data only}
    1. Alin MH, Kihamia CM, Bjorkman A, et al. Efficacy of oral and intravenous artesunate in male Tanzanian adults with Plasmodium falciparum malaria and in vitro susceptibility to artemisinin, chloroquine, and mefloquine. Am J Trop Med Hyg 1995;53(6):639‐45. - PubMed
Anh VNM 92b {unpublished data only}
    1. Anh TK. Open randomised studies to compare the efficacy between three regimens of artemisinin and artemisinin‐mefloquine in uncomplicated falciparum malaria. TDR M20/181/38 TDCRC CRH 04/92.
Ashton VNM (98) {published data only}
    1. Ashton M, Sy ND, Hong N, et al. Artemisinin kinetics and dynamics during oral and rectal treatment of uncomplicated malaria. Clinical Pharmacology and Therapeutics 1998;63(4):482‐93. - PubMed
Batty VNM 96 {published data only}
    1. Batty K, Thu LTA, Davis TME, Ilett KF, Mai TX, et al. A pharmacokinetic and pharmacodynamic study of intravenous vs oral artesunate in uncomplicated falciparum malaria. Br J Clin Pharmacol 1998;45:123‐9. - PMC - PubMed
Bich VNM 93 {published data only}
    1. Nguyen Ngoc Bich, Peter J de Vries, Huyuh Van Thien, Tran Hung Phong, Ngoc Hung, Teunis A Eggelte, et al. Efficacy and tolerance of artemisinin in short combination regimens for the treatment of uncomplicated falciparum malaria. Am J Trop Med Hyg 1996;55(4):438‐43. - PubMed
Bunnag THI (97) {published data only}
    1. Bunnag D, Kanda T, Karbwang J, Pungpak S, Chittamas S, Chalermrut K, et al. Standby treatment for multidrug‐resistant falciparum malaria: combination of artemether and mefloquine. Fifth International Conference on Travel Medicine Program and Abstracts. Geneva, March 24‐27 1997:Fifth International Conference on Travel Medicine. Program and Abstracts; 1997 March 24‐27; Geneva. Abstract 106.
Bunnag THI 89‐90a {published data only}
    1. Bunnag D, Viravan C, Looareesuwan S, Karbwang J, Harinasuta T. Double blind randomised clinical trial of two different regimens of oral artesunate in falciparum malaria. Southeast Asian J Trop Med Public Health 1991;22(4):534‐8. - PubMed
Bunnag THI 89‐90b {published data only}
    1. Bunnag D, Karbwang J, Harinasuta T. Artemether in the treatment of multiple drug resistant falciparum malaria. Southeast Asian J Trop Med Public Health 1992;23(4):762‐7. - PubMed
Chen CHI {unpublished data only}
    1. Chen PO, Guo XB, Li GQN, Song YZ, Wang XH, Pam LT, et al. Effect of dihydroartemisinin on the infectivity of gametocytes (PfG) and a randomised comparison with quinine. Abstract obtained from Guo Qiao Li.
Duarte BRZ 92‐3 {published data only}
    1. Duarte EC, Fontes CJF, Gyorkos TW, Abrahamowicz M. Randomised controlled trial of artesunate plus tetracycline versus standard treatment (quinine plus tetracycline) for uncomplicated malaria in Brazil. Am J Trop Med Hyg 1996;54(2):197‐202. - PubMed
Duc VNM 93 {unpublished data only}
    1. Dao Dinh Duc, Pham Thi Yen, Nguyen Binh, Nguyen Tien Lam, Thanh Nhaun, Nguyen Ba Nen, et al. In vivo and in vitro study on the activities of artemisinin and artemether on uncomplicated falciparum malaria. Obtained from the investigators.
Elhassan SUD 91 {published data only}
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Fu CHI {unpublished data only}
    1. Fu LC, Li GQN, Guo XB, Wang XH, Chen PQ, Jian HX, Li GQ. Dose findings of artesunate treatment of P falciparum malaria. Abstract obtained from Li Guo Qiao.
Fu CHI 88‐90 {published data only}
    1. Fu LC, Guo XB, Fu YX, Li GQ. Clinical studies on the treatment of falciparum malaria with artesunate im injection and a randomly controlled study on artesunate and piperaquine. Clinical trials on Qinghaosu and its derivatives [English translation]. Sanya Tropical Medicine Institute 1990;volume1:66‐71.
Guo CHI (90) {published data only}
    1. Guo XB, Fu LQ, Li GQ. Clinical trials of intramuscular artemether for falciparum malaria treatment [Chinese]. Clinical trials on qinghaosu and its derivatives Sanya Tropical Medicine Institute 1990; Vol. 1:85‐90.
Guo CHI 86a {published data only}
    1. Guo XB, Fu LC, Li GQ. Comparative study of im artemether versus oral piperaquine phosphate. J New Drugs 1989;8:248‐50.
Guo CHI 86b {published data only}
    1. Guo XB, Fu LC, Li GQ. Comparative study of im artemether versus oral pyronaridine complex. Clinical trials on Qinghaosu and its derivatives [English translation] Sanya Tropical Medicine Institute 1990:12‐13.
Hien VNM [2‐4] (94) {published data only}
    1. Hien TT, Arnold K, Hung NT, Loc PP, Dung NT, Cuong BM, et al. Single dose artemisinin‐mefloquine treatment for acute uncomplicated falciparum malaria. Trans R Soc Trop Med Hyg 1994;88:688‐91. - PubMed
Irion GAM(98) {published data only}
    1. Irion A, Abdullah S, Felger I, Beck HP, Mull R, Hatz C. A comparative trial of CGP 56697 and chloroquine in Tanzanian children with subsequent PCR analysis of recurring parasites. Fifth International Conference on Travel Medicine Program and Abstracts. Geneva, March 24‐27 1997:Abstract 107.
    1. Irion A, Abdullah S, Felger I, Mull R, Hatz C, Beck HP. A comparative trial of CGP 56697 and chloroquine in Tanzanian children with subsequent PCR analysis of recurring parasites. British Society for Parasitology 9th malaria meeting. Liverpool, September 1997:Abstract 4.
    1. Irion A, Felger I, Abdulla S, Smith T, Mull R, Tanner M, et al. Distinction of recrudescences from new infections by PCR‐RFLP analysis in a comparative trial of CGP 56697 and chloroquine in Tanzanian children. Trop Med Int Health 1998;3(6):490‐97. - PubMed
Jiang CHI 80 {published data only}
    1. Jiang JB, Guo XB, Li GQ, Kong YC. Antimalarial activity of mefloquine and qinghaosu. Lancet 1982;2(8293):258‐8. - PubMed
Jiao CHI (97) {published data only}
    1. Jiao XQ, Liu EY, Shan CQ, Shan CQ, Dal P, Gathmann I, et al. A double‐blind comparative trial of benflumetol, a novel antimalarial, and CGP 56697, a combination of benflumetol and artemether, in the treatment of acute P. falciparum malaria in adults in China. Fifth International Conference on Travel Medicine Program and Abstracts. Geneva, March 24‐27 1997.
Li CHI (82) {published data only}
    1. Li GQ, et al. Clinical study on use of artemether in treatment of pernicious malaria [Chinese]. Chinese Med J 1982;62(5):293‐4. - PubMed
Li CHI (90) {published data only}
    1. Li GQ, Guo XB, Fu LJ, et al. Clinical report of artesunate intramuscular injection for malaria treatment [Chinese]. Clinical trials on qinghaosu and its derivatives Sanya Tropical Medicine Institute 1990:80‐84.
Li CHI (95) {published data only}
    1. Li X, Yang C. A comparative clinical trial of dihydroarteannuin tablet for 5 day and 7 day course of treatment of falciparum and vivax malaria [Chinese]. J Practical Parasitic Diseases 1995;3(2):66‐8.
Li CHI 85 {published data only}
    1. Li GQ, Guo XB, Fu LC. A randomised comparative study of artesunate versus quinine dihydrochloride in the treatment of falciparum malaria. Clinical trials on Qinghaosu and its derivatives [English translation] Sanya Tropical Medicine Institute 1990:50‐8.
Li CHI a {unpublished data only}
    1. Li GQ, Chen, Li GQN, Wang XH, Trinh KA, Pahm LT, et al. Effect of artesunate on the infectivity of P falciparum gametocytes and a randomised comparative study with quinine. Abstract obtained from Li Guo Qiao.
Li CHI b {unpublished data only}
    1. Li GQN, Wang XH, Guo XB, Fu LC, Jian HX, Li GQ. Dose findings of dihydroartemisinin in treatment of falciparum malaria. Abstract obtained from Li Guo Qiao. - PubMed
Li VNM (95) {unpublished data only}
    1. Li GQ, Wang XH, Guo XB, Jian HX, Anh TK, Thinh PL, et al. Dose findings of dihydroartemisinin on treatment of falciparum malaria and a randomized comparative study with artesunate. Symposium on Tropical Medicine China. 1995:10‐11.
Looareesuwan THI 92a {published data only}
    1. Looareesuwan S, Viravan C, Vanijanonta S, et al. Randomized trial of mefloquine‐doxycycline, and artesunate‐doxycycline for treatment of acute uncomplicated falciparum malaria. Am J Trop Med Hyg 1994;50(6):784‐9. - PubMed
Looareesuwan THI 94 {published data only}
    1. Looareesuwan S, Viravan C, Vanijanonta S, Wilairatana P, Pitisuttithum P, Andrial M. Comparative clinical trial of artesunate followed by mefloquine in the treatment of acute uncomplicated falciparum malaria: two‐ and three‐day regimens. Am J Trop Med Hyg 1996;54(2):210‐13. - PubMed
LuxemburgerTHI‐MYA93 {published data only}
    1. Luxemburger C, Nosten F, Shotar D, Raimond D, Chongsuphajaisiddhi T, White NJ. Oral artesunate in the treatment of uncomplicated hyperparasitaemic falciparum malaria. Am J Trop Med Hyg 1995;53(5);522‐5. - PubMed
Na‐BangchangTHI(96)a {published data only}
    1. Na‐Bangchang K, Kanda T, Tipawangso P, Thanavibul A, Suprakob K, Ibrahim M, Wattanagoon Y, Karbwang J. Activity of artemether‐azithromycin versus artemether‐doxycycline in the treatment of multiple drug resistant falciparum malaria. SE Asian J Trop Med Pub Health 1996;27(3):522‐5. - PubMed
Na‐BangchangTHI(96)b {published data only}
    1. Na‐Bangchang K, Tipwangso P, Thanavibul A, Tan‐ariya P, Suprakob K, Kanda T, Karbwang J. Artemether‐pyrimethamine in the treatment of pyrimethamine‐resistant falciparum malaria. SE Asian J Trop Med Pub Health 1996;27(1):19‐23. - PubMed
Nigeria 1988 {unpublished data only}
    1. Federal Ministry of Health Republic of Nigeria. National Malaria Vector Control Division.
Pang CHI (87) {published data only}
    1. Pang XJ, et al. Combined use of artemether with other antimalarials in treatment of falciparum malaria [Chinese]. Chinese Med J 1987;67(3):137‐9. - PubMed
Price THI 93‐5 {published data only}
    1. Price R, Luxemburger C, Vugt M, Nosten F, Kham A, et al. Artesunate and mefloquine in the treatment of uncomplicated multidrug‐resistant hyperparasitaemic falciparum malaria. Trans R Soc Trop Med Hyg 1998;92:207‐11. - PubMed
QACRG CHI 75 {published data only}
    1. Qinghaosu Antimalaria Co‐ordinating Research Group. Antimalaria studies on qinghaosu. Chinese Med J 1979;92(12):815. - PubMed
SabchareonTHI95‐6 {published data only}
    1. Sabchareon A, Attanath P, Chanthavanich P, Phanuaksook P, Prarinyanupharb V, Poonpanich Y, et al. Comparative clinical trial of artesunate suppositories and oral artesunate in combination with mefloquine in the treatment of children with acute falciparum malaria. Am J Trop Med Hyg 1998;58(1):11‐16. - PubMed
    1. Sabchareon A, Teja‐Isavadharm P, Brewer TG, et al. Clinical and pharmacokinetic comparison of oral versus rectal artesunate in children with uncomplicated falciparum malaria. Program and abstracts of the 45th annual meeting of the American Society for Tropical Medicine and Hygiene. Am J Trop Med Hyg 1996;55(Suppl 2):97.
Shen 1989 {published data only}
    1. Shen Jiaxiang (editor). Phase III trials of artemisinin and its derivatives. Antimalarial drug development in China. Papers presented at a meeting of the Scientific Working Group on the Chemotherapy of Malaria. Beijing: The National Institute of Pharmaceutical Research and Development Beijing, on behalf of the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), April 1989.
Shwe MYA (98) {published data only}
    1. Tin Shwe, Myint Lwin, Soe Aung. Efficacy of artesunate + mefloquine over artesunate alone in community‐based treatment of non‐severe falciparum malaria in Myanmar. Bull WHO 1998;76(2):in press. - PMC - PubMed
Simooya ZIM 91 {published data only}
    1. Simooya O, Mutetwa S, Chandiwana S, et al. A comparative study of the schizontocidal efficacy and safety of artemether versus chloroquine in uncomplicated malaria. Central African Journal Medicine 1992;38(7):257‐63. - PubMed
Sowunmi NIG 93 {published data only}
    1. Sowunmi A, Oduola AMJ, Ilesanmi AO, Salako LA. Open comparison of artemether and mefloquine in uncomplicated Plasmodium falciparum hyperparasitaemia in children. Ann Trop Paed 1996;16:5‐9. - PubMed
Sowunmi NIG 94‐7 {published data only}
    1. Sowunmi A, Oduola AMJ, Ogundahunsi OAT, et al. Randomised trial of artemether versus artemether and mefloquine for the treatment of chloroquine/sulfadoxine‐pyrimethamine‐resistant falciparum malaria during pregnancy. Journal of Obstetrics and Gynaecology 1998;18(4):322‐7. - PubMed
Than MYA 94b {unpublished data only}
    1. Than M. Unpublished data obtained from the investigator, Defence Services General Hospital, Myanmar.
ThanMYA95 {unpublished data only}
    1. Than M. Unpublished data obtained from the investigator, Defence Services General Hospital, Myanmar.
ThanMYA96b {unpublished data only}
    1. Than M. Unpublished data obtained from the investigator, Defence Services General Hospital, Myanmar.
Thwe MYA 93 {unpublished data only}
    1. Thwe Y, Htun YY, Tun KS, Nyunt HH, Yee H, Aung S. Artemether capsule and mefloquine; monotherapies compared to combination therapy. Fourth Myanmar Military Medical Conference. 1994:12.
van Vugt THI 95‐6 {published data only}
    1. Vugt M, Brockman A, Gemperli B, Luxemburger C, Gathmann I, et al. Randomized comparison of artemether‐benflumetol and artesunate‐mefloquine in treatment of multidrug‐resistant falciparum malaria. Antimicrobial Agents and Chemotherapy 1998;42:135‐9. - PMC - PubMed
Wang CHI (81) {published data only}
    1. Wang TY, et al. Clinical observation of treatment of malignant malaria with derivatives of qinghaosu "224" and "242" [Chinese]. Chinese J Internal Med 1981;20(11):673‐5. - PubMed
Wang CHI (95) {unpublished data only}
    1. Wang XH, Guo XB, Jian HX, Fu LC, Li GQ, Anh TK. Randomized comparative study of compound artemisinin and mefloquine + artesunate in treatment of falciparum malaria. Symposium on Tropical Medicine China. 1995:13‐14.
Wang CHI 79‐80 {published data only}
    1. Wang Tongin, Xu Ruchang. Clinical studies of treatment of falciparum malaria with artemether, a derivative of qinghaosu. Journal of Traditional Chinese Medicine [Chinese] 1985;5(4):240‐2. - PubMed
Wang CHI 94 {published data only}
    1. Wang XH, Fu LC, Jian HX, Guo XB, Li GQ, Thinh PL, et al. Randomised comparative study of compound artemisinin tablet and Fansimef in treatment of P falciparum malaria. Clinical trials on Qinghaosu and its derivatives [English translation] Sanya Tropical Medicine Institute 1990:12.
Yen VNM 96 {unpublished data only}
    1. Pham Thi Yen. Final report on the study on efficacy and effectiveness of standard artemisinin 5 day treatment. Institute of Malariology, Parasitology and Entomology (IMPE) Viet Nam 1996:Institute of Malariology, Parasitology and Entomology (IMPE), (1996). Unpublished report.

References to studies awaiting assessment

Anh VNM 92a {unpublished data only}
    1. Anh TK. Open randomised comparison of the efficacy of artemisinin in oral and in suppository formulation versus oral quinine. TDR M20/181/38 TDCRC CRH 04/92.
Bunnag THI (97)b {published and unpublished data}
    1. Bunnag D, Kanda T, Karbwang J, Pungpak S, Cittamas S, Chalermrut K, et al. Proposed standby treatment for multidrug‐resistant falciparum malaria: combination of artemether or artesunate with mefloquine. Fifth International Conference on Travel Medicine Program and Abstracts. Geneva, March 24‐27 1997:Fifth International Conference on Travel Medicine. Program and Abstracts; 1997 March 24‐27; Geneva. Abstract 275.
    1. Bunnag D, Kanda T, Karbwang J, Thimasarn K, Pungpak S, Harinasuta T. Two doses of artemether/mefloquine or artesunate/mefloquine combination for multidrug‐resistant falciparum malaria. S E Asian J Trop Med Pub Health 1997;28(4):727‐30. - PubMed
Coker NIG {unpublished data only}
    1. Coker HAB, Fagbenro‐Beyioku AF, Akinwande JA, Akintonwa A. The efficacy of artemether on normal and chloroquine resistant strains of Plasmodium falciparum in Lagos state of Nigeria. Dragon Pharmaceuticals, UK, unpublished manuscript.
Doherty GAM (99) {published data only}
    1. Doherty JF, Sadiq AD, Bayo L, Alloueche A, Olliaro P, Milligan P, et al. A randomized safety and tolerability trial of artesunate plus sulfadoxine‐pyrimethamine versus sulfadoxine‐pyrimethamine alone for the treatment of uncomplicated malaria in Gambian children. Trans R Soc Trop Med Hyg 1999;93(5):543‐6. - PubMed
Hamisi THI (97) {published data only}
    1. Hamisi MI, Tipangkosol P, Na‐Bangchang K, Wattanagorn Y, Thanavibul A, Suprakob K, et al. Dose finding of the combination artemether + benflumetol in the treatment of acute uncomplicated falciparum malaria. National Institute for Medical Research 15th Annual Joint Scientific Conference Programme and Abstracts. 18‐21 February 1997:Abstract 24.
Honrado THI 94‐5 {published data only}
    1. Honrado ER, Fungladda W, Kamoiratanaku P, Kitayaporn D, Karbwang J, Thimasarn K, et al. Cost‐effectiveness analysis of artesunate and quinine + tetracycline for the treatment of uncomplicated falciparum malaria in Chanthaburi, Thailand. Bull WHO 1999;77(3):235‐43. - PMC - PubMed
LooareesuwanTHI(99) {published data only}
    1. Looareesuwan S, Wilairatana P, Chokejindachai W, Chalermrut K, Wernsdorfer W. A randomized, double‐blind, comparative trial of a new oral combination of artemether and benflumetol (CGP 56697) with mefloquine in the treatment of acute Plasmodium falciparum malaria in Thailand. Am J Trop Med Hyg 1999;60(2):238‐43. - PubMed
Novartis CHI {unpublished data only}
    1. This unpublished study, conducted in Chinese children aged 5‐14 years, comparing artemether monotherapy with co‐artemether (artemether‐benflumetol/lumefantrine) is mentioned in the discussion section of two published reports of co‐artemether trials (Hatz TAZ (98), vonSeidlein GAM 96). The reviewers have been unable to obtain unpublished data from Novartis Pharma A.G.
Price THI (98) {published data only}
    1. Price R, Vugt M, Nosten F, Luxemburger C, Brockman A, Phaipun L, et al. Artesunate versus artemether for the treatment of recrudescent multidrug‐resistant falciparum malaria. Am J Trop Med Hyg 1998;59(6):883‐8. - PubMed
Salcedo BRZ (97) {published data only}
    1. Salcedo JMV, Camargo LMA, Braga MFV, Vanize PSM, Macedo VO. Avaliacao da eficacia do artesunato associado a tetraciclina na terapeutica da malaria falciparum. Revista da Sociedade Brasileira de Medicina Tropical 1997;30(3):215‐22. - PubMed
Villalobos (97) {published data only}
    1. Villalobos SJM, Aranha CLM, De FVB, Soares DMP, De OMV. Effectiveness evaluation of artesunate associated with tetracycline in falciparum malaria therapy. Revista Da Sociedade Brasileira De Medicina Tropical 1997;30(3):215‐22. - PubMed

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Publication types