Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2004;2004(3):CD003341.
doi: 10.1002/14651858.CD003341.pub2.

High first dose quinine regimen for treating severe malaria

Affiliations

High first dose quinine regimen for treating severe malaria

A Lesi et al. Cochrane Database Syst Rev. 2004.

Abstract

Background: Quinine is used for treating severe malaria. There are arguments for giving an initial high dose. We examined the evidence for and against this policy.

Objectives: To assess the clinical outcomes and adverse events of a high first (loading) dose regimen of quinine compared with a uniform (no loading) dose regimen in people with severe malaria.

Search strategy: We searched the Cochrane Infectious Diseases Group's trials register (April 2004), CENTRAL (The Cochrane Library Issue 1, 2004), MEDLINE (1966 to April 2004), EMBASE (1974 to April 2004), LILACS (1982 to April 2004), and conference proceedings for relevant abstracts. We also contacted researchers working in the field and checked the reference lists of all studies.

Selection criteria: Randomized controlled trials comparing a high first (loading) dose of intravenous quinine with a uniform (no loading) dose of intravenous quinine in people with severe malaria.

Data collection and analysis: Two reviewers independently assessed the methodological quality of the trials and extracted data (including adverse event data). We used Review Manager 4.2 to analyse the data: relative risk (RR) for binary data and weighted mean difference (WMD) for continuous data with 95% confidence intervals (CI). We contacted study authors for additional information.

Main results: Four trials (n = 144) met the inclusion criteria. Loading dose was associated with fewer deaths, but this was not statistically significant (RR 0.62, CI 0.19 to 2.04, 3 trials). Loading dose was associated with faster clearance of parasites (WMD -7.44 hours, CI -13.24 to -1.64 hours, 2 trials), resolution of fever (WMD -11.11 hours, CI -20.04 to -2.18 hours, 2 trials). No statistically significant difference was detected for recovery of consciousness, neurological sequelae, or convulsions, but the numbers were small.

Reviewers' conclusions: Quinine loading dose reduced fever clearance time and parasite clearance time. Data are insufficient to directly demonstrate an impact of loading dose on risk of death.

PubMed Disclaimer

Conflict of interest statement

None known.

Figures

1.1
1.1. Analysis
Comparison 1 High first (loading) dose compared with no loading dose, Outcome 1 Death.
1.2
1.2. Analysis
Comparison 1 High first (loading) dose compared with no loading dose, Outcome 2 Coma recovery time.
1.3
1.3. Analysis
Comparison 1 High first (loading) dose compared with no loading dose, Outcome 3 Convulsions.
1.4
1.4. Analysis
Comparison 1 High first (loading) dose compared with no loading dose, Outcome 4 Fever clearance time.
1.5
1.5. Analysis
Comparison 1 High first (loading) dose compared with no loading dose, Outcome 5 Parasite clearance time.
1.6
1.6. Analysis
Comparison 1 High first (loading) dose compared with no loading dose, Outcome 6 Number with asexual parasitaemia at 24 hours.
1.7
1.7. Analysis
Comparison 1 High first (loading) dose compared with no loading dose, Outcome 7 Number with asexual parasitaemia at 48 hours.
1.8
1.8. Analysis
Comparison 1 High first (loading) dose compared with no loading dose, Outcome 8 Neurological sequelae.
1.9
1.9. Analysis
Comparison 1 High first (loading) dose compared with no loading dose, Outcome 9 Adverse events.

Update of

Similar articles

Cited by

References

References to studies included in this review

Assimadi 2002 {published data only}
    1. Assimadi JK, Gbadoe AD, Agbodjan‐Djossou O, Ayewada K, Goeh‐Akue E, Kusiaku K, et al. Intravenous quinine treatment of cerebral malaria in African children: comparison of a loading dose regimen without loading dose [Traitment du paludisme cérébral de l'enfant africain par les sels de quinine: comparaison d'un schéma avec dose charge à un schéma classique sans dose charge]. Archives de Pediatrie 2002;9(6):587‐94. - PubMed
Fargier 1991 {published data only}
    1. Fargier JJ, Louis FJ, Cot M, Maubert B, Hounsinou C, Louis JP, et al. Reducing of coma by quinine loading dose in falciparum cerebral malaria. Lancet 1991;338(8771):896‐7. - PubMed
    1. Louis FJ, Fargier JJ, Maubert B, Louis JP, Hounsinou C, Bras J, et al. Severe malaria attacks in adults in Cameroon: comparison of 2 therapeutic protocols using quinine via parenteral route [Access palustre grave de l'adulte au Cameroun: comparaison de deux protocoles therapeutiques utilisant la quinine par voie parenterale]. Annales de La Societe Belge de Medecine Tropicale 1992;72(3):179‐88. - PubMed
Pasvol 1991 {published data only}
    1. Pasvol G, Newton CRJC, Winstanley PA, Watkins WM, Peshu NM, Were JBO, et al. Quinine treatment of severe falciparum malaria in African children: A randomized comparison of three regimens. American Journal of Tropical Medicine and Hygiene 1991;45(6):702‐13. - PubMed
Tombe 1992 {published data only}
    1. Tombe M, Bhatt KM, Obel AOK. Quinine loading dose in severe falciparum malaria at Kenya National Hospital, Kenya. East African Medical Journal 1992;69(12):670‐4. - PubMed

References to studies excluded from this review

Davis 1988 {published data only}
    1. Davis TM, White NJ, Looareesuwan S, Silamut K, Warrell DA. Quinine pharmacokinetics in cerebral malaria: predicted plasma concentrations after rapid intravenous loading using a two‐compartment model. Transactions of the Royal Society of Tropical Medicine and Hygiene 1988;82(4):542‐7. - PubMed
Davis 1990 {published data only}
    1. Davis TME, Supanaranond W, Pukrittayakamee S, Karbwang J, Molunto P, Mekthon S, et al. A safe and effective consecutive‐infusion regimen for rapid quinine loading in severe falciparum malaria. Journal of Infectious Diseases 1990;161(6):1305‐8. - PubMed
Mehta 1994 {published data only}
    1. Mehta SR, Lazar AI, Kasthuri AS. Experience on loading dose‐‐quinine therapy in cerebral malaria. Journal of Association of Physicians in India 1994;42(5):376‐8. - PubMed
van der Torn 1998 {published data only}
    1. Torn M, Thuma PE, Mabeza GF, Biemba G, Moyo VM, McLaren CE, et al. Loading dose of quinine in African children with cerebral malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 1998;92(3):325‐31. - PubMed
White 1983 {published data only}
    1. White NJ, Looareesuwan S, Warrell DA, Warrell MJ, Chanthavanich P, Bunnag D, et al. Quinine loading dose in cerebral malaria. American Journal of Tropical Medicine and Hygiene 1983;32(1):1‐5. - PubMed
Winstanley 1994 {published data only}
    1. Winstanley PA, Mberu EK, Watkin WM, Murphy SA, Lowe B, Marsh K. Towards optimal regimens of parenteral quinine of young African children with cerebral malaria: unbound quinine concentrations following a single loading dose regimen. Transactions of the Royal Society of Tropical Medicine and Hygiene 1994;88(5):577‐80. - PubMed

Additional references

Alderson 2004
    1. Alderson P, Green S, Higgins J, editors. Highly sensitive search strategies for identifying reports of randomized controlled trials in MEDLINE. Cochrane Reviewer's Handbook 4.2.2 [updated March 2004]; Appendix 5b. In: The Cochrane Library. The Cochrane Collaboration. Chichester, UK: John Wiley & Sons, Ltd.; 2004, Issue 2.
Allen 1996
    1. Allen SJ, O'Donnell A, Alexander ND, Clegg JB. Severe malaria in children in Papua New Guinea. Quarterly Journal of Medicine 1996;89(10):779‐88. - PubMed
Bjorkman 1990
    1. Bjorkman A, Phillips‐Howard PA. The epidemiology of drug resistant malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 1990;84(2):177‐80. - PubMed
Chongsuphajaisiddhi 1981
    1. Chongsuphajaisiddhi T, Sabcharoen A, Attanath P. In vivo and in vitro sensitivity of falciparum malaria to quinine in Thai children. Annals of Tropical Paediatrics 1981;1(1):21‐6. - PubMed
Dorland 2000
    1. Dorland WAN. Cinchonism. Dorland's illustrated medical dictionary. 29th Edition. Philadelphia: W.B. Saunders Co, 2000:354.
Hall 1977
    1. Hall AP. The treatment of severe falciparum malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 1977;71(5):367‐79. - PubMed
Jacqz‐Aigrain 1994
    1. Jacqz‐Aigrain E, Bennasr S, Desplanques L, Peralma A, Beaufils F. Severe poisoning risk linked to intravenous administration of quinine. Archives de Pediatrie 1994;1(1):14‐9. - PubMed
Jaffar 1997
    1. Jaffar S, Hensbroek MB, Palmer A, Schneider G, Greenwood B. Predictors of fatal outcome following childhood cerebral malaria. American Journal of Tropical Medicine and Hygiene 1997;57(1):20‐4. - PubMed
Jüni 2001
    1. Jüni P, Altman DG, Egger M. Systematic reviews in healthcare: Assessing the quality of controlled clinical trials. BMJ 2001;323(7303):42‐6. - PMC - PubMed
Kawo 1991
    1. Kawo NG, Msengi AE, Swai AB, Orskov H, Alberti KG, McLarty DG. The metabolic effects of quinine in children with severe and complicated Plasmodium falciparum malaria in Dar es Salaam. Transactions of the Royal Society of Tropical Medicine and Hygiene 1991;85(6):711‐3. - PubMed
Nuwaha 2001
    1. Nuwaha F. The challenge of chloroquine‐resistant malaria in sub‐Saharan Africa. Health Policy Plan 2001;16(1):1‐12. - PubMed
Parmar 1998
    1. Parmar MKB, Torri V, Stewart L. Extracting summary statistics to perform meta‐analyses of the published literature for survival endpoints. Statistics in Medicine 1998;17(24):2815‐34. - PubMed
Phillips 1984
    1. Phillips RE. Management of Plasmodium falciparum malaria. Medical Journal of Australia 1984;141(8):511‐7. - PubMed
Phillips 1996
    1. Phillips M, Phillips‐Howard PA. Economic implications of resistance to antimalarial drugs. Pharmacoeconomics 1996;10(3):225‐38. - PubMed
Review Manager 5 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.0. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2008.
Schellenberg 1999
    1. Schellenberg D, Menendez C, Kahigwa E, Font F, Galindo C, Acosta C, et al. African children with malaria in an area of intense Plasmodium falciparum transmission: features on admission to the hospital and risk factors for death. American Journal of Tropical Medicine and Hygiene 1999;61(3):431‐8. - PubMed
Schulz 1995
    1. Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995;273(5):408‐12. - PubMed
Sharma 1989
    1. Sharma AM, Keller F, Boeckh M, Heitz J, Borner K. Quinine dosage in severe malaria with renal failure necessitating haemodialysis. European Journal of Clinical Pharmacology 1989;36(5):535‐6. - PubMed
Trape 1998
    1. Trape JF, Pison G, Preziosi MP, Enel C, Desgrees du Lou A, Delaunay V, et al. Impact of chloroquine resistance on malaria mortality. Comptes Rendus de l'Academie Sciences. Series III 1998;321(8):689‐97. - PubMed
van Hensbroek 1996
    1. Hensbroek MB, Kwiatowski D, Berg B, Hoek FJ, Boxtel CJ, Kager PA. Quinine pharmacokinetics in young children with severe malaria. American Journal of Tropical Medicine and Hygiene 1996;54(3):237‐42. - PubMed
Waller 1990
    1. Waller D, Krishna S, Craddock C, Brewster D, Jammeh A, Kwiatkowski D, et al. The pharmacokinetic properties of intramuscular quinine in Gambian children with severe falciparum malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 1990;84(4):488‐91. - PubMed
White 1982
    1. White NJ, Looaresuwan S, Warrell DA, Warrell MJ, Bunnag D, Harinasuta T. Quinine pharmacokinetics and toxicity in cerebral and uncomplicated falciparum malaria. American Journal of Medicine 1982;73:564‐72. - PubMed
White 1989
    1. White NJ, Krishna S, Waller D, Craddock C, Kwiatkowski D, Brewster D. Open comparison of intramuscular chloroquine and quinine in children with severe chloroquine‐sensitive falciparum malaria. Lancet 1989;2(8675):1313‐6. - PubMed
WHO 1986
    1. World Health Organization Malaria Action Programme. Severe and complicated malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 1986;80 Suppl 3:1‐50. - PubMed
WHO 1990a
    1. World Health Organization. World malaria situation, 1988. Division of Control of Tropical Diseases. World Health Statistics Quarterly 1990;43(2):68‐79. - PubMed
WHO 1990b
    1. World Health Organization. Severe and complicated malaria. World Health Organization, Division of Control of Tropical Diseases. Transactions of the Royal Society of Tropical Medicine and Hygiene 1990;84 Suppl 2:1‐65. - PubMed
WHO 1996
    1. World Health Organization. The world health report. 1996. Fighting disease. Fostering development. Report of the Director‐General. Geneva: World Health Organization, 1996.
WHO 2000
    1. World Health Organization. Severe falciparum malaria. World Health Organization, Communicable Diseases Cluster. Transactions of the Royal Society of Tropical Medicine and Hygiene 2000;94 Suppl 1:1‐90. - PubMed

Publication types