title: Diagnosis and treatment based on quantitative PCR after controlled human malaria infection.
abstract: Controlled human malaria infection (CHMI) has become well-established in the evaluation of drugs and vaccines. Anti-malarial treatment is usually initiated when thick blood smears are positive by microscopy. This study explores the effects of using the more sensitive qPCR as the primary diagnostic test.
  
  
  
  1691 diagnostic blood samples were analysed by microscopy and qPCR from 115 volunteers (55 malaria naïve and 60 having received chemoprophylaxis and sporozoite immunization) who were challenged by five mosquitoes infected with Plasmodium falciparum sporozoites of the NF54 strain.
  
  
  
  Retrospective analysis of different qPCR criteria for diagnosis and treatment, showed that once daily qPCR (threshold 100 parasites/ml) had 99 % sensitivity and 100 % specificity, and shortened the median prepatent period from 10.5 to 7.0 days after CHMI when compared to twice daily measurement of thick blood smears (threshold 4000 parasites/ml). This is expected to result in a 78 % decrease of adverse events before initiation of treatment in future studies. Trial outcome related to infection and protective efficacy remained unchanged.
  
  
  
  The use of qPCR as the primary diagnostic test in CHMI decreases symptoms as well as parasitaemia while obviating the need for twice daily follow-up. The implementation improves safety while reducing the clinical burden and costs without compromising the evaluation of protective efficacy.
authors: Department of Medical Microbiology and Radboud Center for Infectious Diseases, Radboud university medical center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors: Jona
authors: J
authors: Walk
authors: Department of Infectious Diseases, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands.
authors: Remko
authors: R
authors: Schats
authors: Department of Infectious Diseases, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands.
authors: Marijke C C
authors: MC
authors: Langenberg
authors: Department of Medical Microbiology and Radboud Center for Infectious Diseases, Radboud university medical center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors: Isaie J
authors: IJ
authors: Reuling
authors: Department of Medical Microbiology and Radboud Center for Infectious Diseases, Radboud university medical center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors: Karina
authors: K
authors: Teelen
authors: Department of Medical Microbiology and Radboud Center for Infectious Diseases, Radboud university medical center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors: Meta
authors: M
authors: Roestenberg
authors: Department of Medical Microbiology and Radboud Center for Infectious Diseases, Radboud university medical center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors: Cornelus C
authors: CC
authors: Hermsen
authors: Department of Infectious Diseases, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands.
authors: Leo G
authors: LG
authors: Visser
authors: Department of Medical Microbiology and Radboud Center for Infectious Diseases, Radboud university medical center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. Robert.Sauerwein@radboudumc.nl.
authors: Robert W
authors: RW
authors: Sauerwein
mesh_terms: D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000627:therapeutic use*; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000175:diagnosis* / Q000188:drug therapy*; D008297:Male; D008853:Microscopy; D010963:Plasmodium falciparum / Q000302:isolation & purification*; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D013997:Time Factors; D016896:Treatment Outcome; D014838:Volunteers; D055815:Young Adult
chemical_list: D000962:Antimalarials
keywords: Controlled human malaria infection (CHMI); Malaria; Plasmodium falciparum; quantitative PCR (qPCR)