title: Factors determining the occurrence of submicroscopic malaria infections and their relevance for control.
abstract: Malaria parasite prevalence in endemic populations is an essential indicator for monitoring the progress of malaria control, and has traditionally been assessed by microscopy. However, surveys increasingly use sensitive molecular methods that detect higher numbers of infected individuals, questioning our understanding of the true infection burden and resources required to reduce it. Here we analyse a series of data sets to characterize the distribution and epidemiological factors associated with low-density, submicroscopic infections. We show that submicroscopic parasite carriage is common in adults, in low-endemic settings and in chronic infections. We find a strong, non-linear relationship between microscopy and PCR prevalence in population surveys (n=106), and provide a tool to relate these measures. When transmission reaches very low levels, submicroscopic carriers are estimated to be the source of 20-50% of all human-to-mosquito transmissions. Our findings challenge the idea that individuals with little previous malaria exposure have insufficient immunity to control parasitaemia and suggest a role for molecular screening.
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK. l.okell@imperial.ac.uk
authors.forename: Lucy C
authors.initials: LC
authors.lastname: Okell
authors.forename: Teun
authors.initials: T
authors.lastname: Bousema
authors.forename: Jamie T
authors.initials: JT
authors.lastname: Griffin
authors.forename: André Lin
authors.initials: AL
authors.lastname: Ouédraogo
authors.forename: Azra C
authors.initials: AC
authors.lastname: Ghani
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Drakeley
mesh_terms: D056704:Adaptive Immunity; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000818:Animals; D000852:Anopheles / Q000469:parasitology; D002353:Carrier State / Q000453:epidemiology* / Q000469:parasitology / Q000517:prevention & control; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007303:Insect Vectors / Q000469:parasitology; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000469:parasitology / Q000517:prevention & control / Q000635:transmission; D008297:Male; D008853:Microscopy; D008875:Middle Aged; D010963:Plasmodium falciparum; D016133:Polymerase Chain Reaction; D015995:Prevalence; D012680:Sensitivity and Specificity; D055815:Young Adult