Skip to main content
Top
Published in: Malaria Journal 1/2006

Open Access 01-12-2006 | Research

The use of genotyping in antimalarial clinical trials: a systematic review of published studies from 1995–2005

Authors: William J Collins, Bryan Greenhouse, Philip J Rosenthal, Grant Dorsey

Published in: Malaria Journal | Issue 1/2006

Login to get access

Abstract

Background

The use of genotyping to distinguish recrudescent from new infections is currently recommended for all clinical antimalarial efficacy trials by the World Health Organization. However, genotyping-adjusted drug efficacy estimates may vary between trials due to the use of different genotyping methods and to the different settings in which these methods are applied.

Methods

A systematic review of all clinical antimalarial efficacy trials published from 1995–2005 was performed to characterize the use of genotyping, including the methods used and the effect of these methods on estimates of drug efficacy.

Results

In a multivariate analysis, the method of interpretation of genotyping results, the studied therapy, the location of the trial, and the duration of study follow-up all had statistically significant effects on the percent of genotyped outcomes classified as new infections.

Conclusion

Criteria for defining appropriate, standardized genotyping methods for use in different settings are needed to enable more accurate estimates of antimalarial drug efficacy and better comparison between trials. The advantages and disadvantages of different genotyping methods and their potential impact in various settings are discussed.
Appendix
Available only for authorised users
Literature
4.
go back to reference Farnert A, Arez AP, Babiker HA, Beck HP, Benito A, Bjorkman A, Bruce MC, Conway DJ, Day KP, Henning L, Mercereau-Puijalon O, Ranford-Cartwright LC, Rubio JM, Snounou G, Walliker D, Zwetyenga J, do Rosario VE: Genotyping of Plasmodium falciparum infections by PCR: a comparative multicentre study. Trans R Soc Trop Med Hyg. 2001, 95: 225-232. 10.1016/S0035-9203(01)90175-0.CrossRefPubMed Farnert A, Arez AP, Babiker HA, Beck HP, Benito A, Bjorkman A, Bruce MC, Conway DJ, Day KP, Henning L, Mercereau-Puijalon O, Ranford-Cartwright LC, Rubio JM, Snounou G, Walliker D, Zwetyenga J, do Rosario VE: Genotyping of Plasmodium falciparum infections by PCR: a comparative multicentre study. Trans R Soc Trop Med Hyg. 2001, 95: 225-232. 10.1016/S0035-9203(01)90175-0.CrossRefPubMed
5.
go back to reference Slater M, Kiggundu M, Dokomajilar C, Kamya MR, Bakyaita N, Talisuna A, Rosenthal PJ, Dorsey G: Distinguishing recrudescences from new infections in antimalarial clinical trials: major impact of interpretation of genotyping results on estimates of drug efficacy. Am J Trop Med Hyg. 2005, 73: 256-262.PubMed Slater M, Kiggundu M, Dokomajilar C, Kamya MR, Bakyaita N, Talisuna A, Rosenthal PJ, Dorsey G: Distinguishing recrudescences from new infections in antimalarial clinical trials: major impact of interpretation of genotyping results on estimates of drug efficacy. Am J Trop Med Hyg. 2005, 73: 256-262.PubMed
6.
go back to reference Plowe CV, Djimde A, Bouare M, Doumbo O, Wellems TE: Pyrimethamine and proguanil resistance-conferring mutations in Plasmodium falciparum dihydrofolate reductase: polymerase chain reaction methods for surveillance in Africa. Am J Trop Med Hyg. 1995, 52: 565-568.PubMed Plowe CV, Djimde A, Bouare M, Doumbo O, Wellems TE: Pyrimethamine and proguanil resistance-conferring mutations in Plasmodium falciparum dihydrofolate reductase: polymerase chain reaction methods for surveillance in Africa. Am J Trop Med Hyg. 1995, 52: 565-568.PubMed
7.
go back to reference Cattamanchi A, Kyabayinze D, Hubbard A, Rosenthal PJ, Dorsey G: Distinguishing recrudescence from reinfection in a longitudinal antimalarial drug efficacy study: comparison of results based on genotyping of msp-1, msp-2, and glurp. Am J Trop Med Hyg. 2003, 68: 133-139.PubMed Cattamanchi A, Kyabayinze D, Hubbard A, Rosenthal PJ, Dorsey G: Distinguishing recrudescence from reinfection in a longitudinal antimalarial drug efficacy study: comparison of results based on genotyping of msp-1, msp-2, and glurp. Am J Trop Med Hyg. 2003, 68: 133-139.PubMed
8.
go back to reference Snounou G, Beck HP: The use of PCR genotyping in the assessment of recrudescence or reinfection after antimalarial drug treatment. Parasitol Today (Personal ed. 1998, 14: 462-467. 10.1016/S0169-4758(98)01340-4.CrossRef Snounou G, Beck HP: The use of PCR genotyping in the assessment of recrudescence or reinfection after antimalarial drug treatment. Parasitol Today (Personal ed. 1998, 14: 462-467. 10.1016/S0169-4758(98)01340-4.CrossRef
9.
go back to reference Brockman A, Paul RE, Anderson TJ, Hackford I, Phaiphun L, Looareesuwan S, Nosten F, Day KP: Application of genetic markers to the identification of recrudescent Plasmodium falciparum infections on the northwestern border of Thailand. Am J Trop Med Hyg. 1999, 60: 14-21.PubMed Brockman A, Paul RE, Anderson TJ, Hackford I, Phaiphun L, Looareesuwan S, Nosten F, Day KP: Application of genetic markers to the identification of recrudescent Plasmodium falciparum infections on the northwestern border of Thailand. Am J Trop Med Hyg. 1999, 60: 14-21.PubMed
10.
go back to reference Ashley EA, McGready R, Hutagalung R, Phaiphun L, Slight T, Proux S, Thwai KL, Barends M, Looareesuwan S, White NJ, Nosten F: A randomized, controlled study of a simple, once-daily regimen of dihydroartemisinin-piperaquine for the treatment of uncomplicated, multidrug-resistant falciparum malaria. Clin Infect Dis. 2005, 41: 425-432. 10.1086/432011.CrossRefPubMed Ashley EA, McGready R, Hutagalung R, Phaiphun L, Slight T, Proux S, Thwai KL, Barends M, Looareesuwan S, White NJ, Nosten F: A randomized, controlled study of a simple, once-daily regimen of dihydroartemisinin-piperaquine for the treatment of uncomplicated, multidrug-resistant falciparum malaria. Clin Infect Dis. 2005, 41: 425-432. 10.1086/432011.CrossRefPubMed
11.
go back to reference Mayxay M, Thongpraseuth V, Khanthavong M, Lindegardh N, Barends M, Keola S, Pongvongsa T, Phompida S, Phetsouvanh R, Stepniewska K, White NJ, Newton PN: An open, randomized comparison of artesunate plus mefloquine vs. dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in the Lao People's Democratic Republic (Laos). Trop Med Int Health. 2006, 11: 1157-1165. 10.1111/j.1365-3156.2006.01671.x.CrossRefPubMed Mayxay M, Thongpraseuth V, Khanthavong M, Lindegardh N, Barends M, Keola S, Pongvongsa T, Phompida S, Phetsouvanh R, Stepniewska K, White NJ, Newton PN: An open, randomized comparison of artesunate plus mefloquine vs. dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in the Lao People's Democratic Republic (Laos). Trop Med Int Health. 2006, 11: 1157-1165. 10.1111/j.1365-3156.2006.01671.x.CrossRefPubMed
12.
go back to reference Smithuis F, Kyaw MK, Phe O, Aye KZ, Htet L, Barends M, Lindegardh N, Singtoroj T, Ashley E, Lwin S, Stepniewska K, White NJ: Efficacy and effectiveness of dihydroartemisinin-piperaquine versus artesunate-mefloquine in falciparum malaria: an open-label randomised comparison. Lancet. 2006, 367: 2075-2085. 10.1016/S0140-6736(06)68931-9.CrossRefPubMed Smithuis F, Kyaw MK, Phe O, Aye KZ, Htet L, Barends M, Lindegardh N, Singtoroj T, Ashley E, Lwin S, Stepniewska K, White NJ: Efficacy and effectiveness of dihydroartemisinin-piperaquine versus artesunate-mefloquine in falciparum malaria: an open-label randomised comparison. Lancet. 2006, 367: 2075-2085. 10.1016/S0140-6736(06)68931-9.CrossRefPubMed
13.
go back to reference Karema C, Fanello CI, Van Overmeir C, Van Geertruyden JP, van Doren W, Ngamije D, D'Alessandro U: Safety and efficacy of dihydroartemisinin/piperaquine (Artekin((R))) for the treatment of uncomplicated Plasmodium falciparum malaria in Rwandan children. Trans R Soc Trop Med Hyg. 2006, 100: 1105-1111. 10.1016/j.trstmh.2006.01.001.CrossRefPubMed Karema C, Fanello CI, Van Overmeir C, Van Geertruyden JP, van Doren W, Ngamije D, D'Alessandro U: Safety and efficacy of dihydroartemisinin/piperaquine (Artekin((R))) for the treatment of uncomplicated Plasmodium falciparum malaria in Rwandan children. Trans R Soc Trop Med Hyg. 2006, 100: 1105-1111. 10.1016/j.trstmh.2006.01.001.CrossRefPubMed
14.
go back to reference Rwagacondo CE, Karema C, Mugisha V, Erhart A, Dujardin JC, Van Overmeir C, Ringwald P, D'Alessandro U: Is amodiaquine failing in Rwanda? Efficacy of amodiaquine alone and combined with artesunate in children with uncomplicated malaria. Trop Med Int Health. 2004, 9: 1091-1098. 10.1111/j.1365-3156.2004.01316.x.CrossRefPubMed Rwagacondo CE, Karema C, Mugisha V, Erhart A, Dujardin JC, Van Overmeir C, Ringwald P, D'Alessandro U: Is amodiaquine failing in Rwanda? Efficacy of amodiaquine alone and combined with artesunate in children with uncomplicated malaria. Trop Med Int Health. 2004, 9: 1091-1098. 10.1111/j.1365-3156.2004.01316.x.CrossRefPubMed
15.
go back to reference Mugittu K, Adjuik M, Snounou G, Ntoumi F, Taylor W, Mshinda H, Olliaro P, Beck HP: Molecular genotyping to distinguish between recrudescents and new infections in treatment trials of Plasmodium falciparum malaria conducted in Sub-Saharan Africa: adjustment of parasitological outcomes and assessment of genotyping effectiveness. Trop Med Int Health. 2006, 11: 1350-1359. 10.1111/j.1365-3156.2006.01688.x.CrossRefPubMed Mugittu K, Adjuik M, Snounou G, Ntoumi F, Taylor W, Mshinda H, Olliaro P, Beck HP: Molecular genotyping to distinguish between recrudescents and new infections in treatment trials of Plasmodium falciparum malaria conducted in Sub-Saharan Africa: adjustment of parasitological outcomes and assessment of genotyping effectiveness. Trop Med Int Health. 2006, 11: 1350-1359. 10.1111/j.1365-3156.2006.01688.x.CrossRefPubMed
16.
go back to reference Nyachieo A, Van Overmeir C, Laurent T, Dujardin JC, D'Alessandro U: Plasmodium falciparum genotyping by microsatellites as a method to distinguish between recrudescent and new infections. Am J Trop Med Hyg. 2005, 73: 210-213.PubMed Nyachieo A, Van Overmeir C, Laurent T, Dujardin JC, D'Alessandro U: Plasmodium falciparum genotyping by microsatellites as a method to distinguish between recrudescent and new infections. Am J Trop Med Hyg. 2005, 73: 210-213.PubMed
Metadata
Title
The use of genotyping in antimalarial clinical trials: a systematic review of published studies from 1995–2005
Authors
William J Collins
Bryan Greenhouse
Philip J Rosenthal
Grant Dorsey
Publication date
01-12-2006
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2006
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-5-122

Other articles of this Issue 1/2006

Malaria Journal 1/2006 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.