Impact of microscopy error on estimates of protective efficacy in malaria-prevention trials.
Microscopy is an imperfect reference standard used for malaria diagnosis in clinical trials. The purpose of this study was to provide an assessment of the accuracy of basic microscopy, to compare polymerase chain reaction (PCR)-based diagnosis with microscopy results, and to assess the effect of microscopy error on apparent protective efficacy. The sensitivity and specificity of basic, compared with expert, microscopy was determined to be 91% and 71%, respectively. In a clinical trial, agreement between PCR and microscopy results improved with expert confirmation of initial results. In a simulated 12-week trial with weekly routine malaria smears, a very high specificity (>99%) for each malaria smear was found to be necessary for an estimate of protective efficacy to be within 10%-25% of the true value, but sensitivity had little effect on this estimate. Microscopy error occurs and can affect clinical trial results.
Division of Experimental Therapeutics, Silver Spring, Maryland 20910-7500, USA. Colin.Ohrt@na.amedd.army.mil
Colin
C
Ohrt
Purnomo
M Awalludin
MA
Sutamihardja
Douglas
D
Tang
Kevin C
KC
Kain
D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use; D003951:Diagnostic Errors; D004311:Double-Blind Method; D004318:Doxycycline / Q000627:therapeutic use; D006801:Humans; D016778:Malaria, Falciparum / Q000175:diagnosis* / Q000469:parasitology / Q000517:prevention & control; D016780:Malaria, Vivax / Q000175:diagnosis* / Q000469:parasitology / Q000517:prevention & control; D015767:Mefloquine / Q000627:therapeutic use; D008853:Microscopy / Q000379:methods*; D008889:Military Personnel; D010963:Plasmodium falciparum / Q000235:genetics / Q000302:isolation & purification; D010966:Plasmodium vivax / Q000235:genetics / Q000302:isolation & purification; D016133:Polymerase Chain Reaction / Q000379:methods; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012015:Reference Standards; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D000962:Antimalarials; D004318:Doxycycline; D015767:Mefloquine