The perils of PCR: can we accurately 'correct' antimalarial trials?

被引:42
作者
Juliano, Jonathan J. [4 ]
Gadalla, Nahla [2 ,3 ]
Sutherland, Colin J. [2 ,3 ]
Meshnick, Steven R. [1 ]
机构
[1] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA
[2] Hosp Trop Dis, Dept Clin Parasitol, London WC1E 6JB, England
[3] Univ London London Sch Hyg & Trop Med, Dept Infect & Trop Dis, London WC1E 7HT, England
[4] Univ N Carolina, Sch Med, Dept Med, Div Infect Dis, Chapel Hill, NC 27599 USA
关键词
PLASMODIUM-FALCIPARUM MALARIA; HETERODUPLEX TRACKING ASSAY; POLYMERASE-CHAIN-REACTION; CLINICAL-TRIALS; ARTEMETHER-LUMEFANTRINE; POPULATION-DYNAMICS; INFECTIONS; PARASITES; EFFICACY; RECRUDESCENCE;
D O I
10.1016/j.pt.2009.12.007
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
07 ; 0710 ; 09 ; 100103 ;
摘要
During follow-up in antimalarial drug trials, treated subjects can be newly infected. PCR correction is used to distinguish this re-infection from drug failure (recrudescence) and to adjust final drug efficacy estimates. The epidemiological, biological and technical limitations of PCR correction and how this can lead to misclassification in drug trial outcomes are underappreciated. This article considers these limitations and proposes a framework for reporting, interpreting and improving PCR correction of antimalarial trials.
引用
收藏
页码:119 / 124
页数:6
相关论文
共 46 条
[31]   Determination of failure of treatment of Plasmodium falciparum infection by using polymerase chain reaction single-strand conformational polymorphism fingerprinting [J].
Ohrt, C ;
Mirabelli-Primdahl, L ;
Looareesuwan, S ;
Wilairatana, P ;
Walsh, D ;
Kain, KC .
CLINICAL INFECTIOUS DISEASES, 1999, 28 (04) :847-852
[32]   Failure of artesunate-mefloquine combination therapy for uncomplicated Plasmodium falciparum malaria in southern Cambodia [J].
Rogers, William O. ;
Sem, Rithy ;
Tero, Thong ;
Chim, Pheaktra ;
Lim, Pharath ;
Muth, Sinuon ;
Socheat, Duong ;
Ariey, Frederic ;
Wongsrichanalai, Chansuda .
MALARIA JOURNAL, 2009, 8
[33]   Identification and recovery of minor HIV-1 variants using the heteroduplex tracking assay and biotinylated probes [J].
Schnell, Gretja ;
Ince, William L. ;
Swanstrom, Ronald .
NUCLEIC ACIDS RESEARCH, 2008, 36 (22) :e146
[34]   The role of pfmdr1 in Plasmodium falciparum tolerance to artemether-lumefantrine in Africa [J].
Sisowath, Christin ;
Ferreira, Pedro E. ;
Bustamante, Leyla Y. ;
Dahlstrom, Sabina ;
Martensson, Andreas ;
Bjorkman, Anders ;
Krishna, Sanjeev ;
Gil, Jose P. .
TROPICAL MEDICINE & INTERNATIONAL HEALTH, 2007, 12 (06) :736-742
[35]   Distinguishing recrudescences from new infections in antimalarial clinical trials: Major impact of interpretation of genotyping results on estimates of drug efficacy [J].
Slater, M ;
Kiggundu, M ;
Dokomajilar, C ;
Kamya, MR ;
Bakyaita, N ;
Talisuna, A ;
Rosenthal, PJ ;
Dorsey, G .
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 2005, 73 (02) :256-262
[36]   The use of PCR genotyping in the assessment of recrudescence or reinfection after antimalarial drug treatment [J].
Snounou, G ;
Beck, HP .
PARASITOLOGY TODAY, 1998, 14 (11) :462-467
[37]   Some considerations in the design and interpretation of antimalarial drug trials in uncomplicated falciparum malaria [J].
Stepniewska, Kasia ;
White, Nicholas J. .
MALARIA JOURNAL, 2006, 5 (1)
[38]   Comparing Highly Efficacious Antimalarial Drugs [J].
Sutherland, Colin J. .
PLOS MEDICINE, 2008, 5 (11) :1544-1545
[39]   Mutations in the Plasmodium falciparum cytochrome b gene are associated with delayed parasite recrudescence in malaria patients treated with atovaquone-proguanil [J].
Sutherland, Colin J. ;
Laundy, Matt ;
Price, Nicholas ;
Burke, Martina ;
Fivelman, Quinton L. ;
Pasvol, Geoffrey ;
Klein, John L. ;
Chiodini, Peter L. .
MALARIA JOURNAL, 2008, 7 (1)
[40]   Novel pfdhps Haplotypes among Imported Cases of Plasmodium falciparum Malaria in the United Kingdom [J].
Sutherland, Colin J. ;
Fifer, Helen ;
Pearce, Richard J. ;
bin Reza, Faisal ;
Nicholas, Meredydd ;
Haustein, Thomas ;
Njimgye-Tekumafor, Njah E. ;
Doherty, Justin F. ;
Gothard, Philip ;
Polley, Spencer D. ;
Chiodini, Peter L. .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2009, 53 (08) :3405-3410