title: Immunophoretic rapid diagnostic tests as a source of immunoglobulins for estimating malaria sero-prevalence and transmission intensity.
abstract: BACKGROUND
  Sero-epidemiological methods are being developed as a tool for rapid assessment of malaria transmission intensity. Simple blood collection methods for use in field settings will make this more feasible. This paper describes validation of such a method, by analysing immunoglobulins from blood retained within immunophoretic rapid diagnostic tests (RDTs) for Plasmodium falciparum. RDTs are now widely used for the diagnosis of malaria and estimation of parasite rates, and this method represents a further use for these devices in malaria control.
  
  
  METHODS
  Immunoglobulins eluted from RDTs, designed to detect parasite histidine rich protein-2 (HRP-2), were analysed by indirect ELISA for IgG recognizing the P. falciparum blood stage antigens merozoite surface protein-1(19) (MSP-1(19)) and apical membrane antigen-1 (AMA-1). Optimal storage conditions for RDTs were evaluated by comparing antibody responses from RDTs stored in dry or humid conditions at 4 degrees C or at ambient temperature (with or without air-conditioning) for 7, 31 or 70 days. Antibody levels estimated using 3,700 RDT samples from attendees at health facilities in North-eastern Tanzania were compared with contemporaneously collected filter paper blood spots (FPBS) and used to estimate seroconversion rates.
  
  
  RESULTS
  Storage of RDTs at 4 degrees C was optimal for immunoglobulin recovery but short-term storage at ambient temperatures did not substantially affect anti-malarial IgG levels. Results from RDTs were comparable with those from FPBSs, for both antigens. RDT-generated titres tended to be slightly higher than those generated from FPBSs, possibly due to greater recovery of immunoglobulins from RDTs compared to filter paper. Importantly, however, RDT-based seroconversion rates, and hence serological estimates of malaria transmission intensity, agreed closely with those from FPBSs.
  
  
  CONCLUSIONS
  RDTs represent a practical option for collecting blood for sero-epidemiological surveys, with potential cost and logistical advantages over filter paper and other blood collection methods. RDT-based seroepidemiology can be incorporated into routine monitoring of malaria endemicity, providing information to supplement parasite prevalence rates and generating rapid, robust assessment of malaria transmission intensity at minimal extra cost.
authors.affiliation: Joint Malaria Programme, Kilimanjaro Christian Medical Centre, Moshi, Tanzania. geoff.williams@mrc-lmb.cam.ac.uk
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Williams
authors.forename: Clement
authors.initials: C
authors.lastname: Mweya
authors.forename: Laveta
authors.initials: L
authors.lastname: Stewart
authors.forename: George
authors.initials: G
authors.lastname: Mtove
authors.forename: Hugh
authors.initials: H
authors.lastname: Reyburn
authors.forename: Jackie
authors.initials: J
authors.lastname: Cook
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Corran
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Riley
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Drakeley
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000953:Antigens, Protozoan / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003955:Diagnostic Tests, Routine / Q000191:economics / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G; D007155:Immunologic Factors; D007223:Infant; D016778:Malaria, Falciparum / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D008297:Male; D008565:Membrane Proteins / Q000097:blood*; D020066:Merozoite Surface Protein 1 / Q000097:blood*; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000302:isolation & purification*; D015995:Prevalence; D015800:Protozoan Proteins / Q000097:blood*; D011933:Reagent Kits, Diagnostic / Q000592:standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016036:Seroepidemiologic Studies; D013636:Tanzania / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000953:Antigens, Protozoan; C514457:HRP-2 antigen, Plasmodium falciparum; D007074:Immunoglobulin G; D007155:Immunologic Factors; D008565:Membrane Proteins; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; D011933:Reagent Kits, Diagnostic; C090077:apical membrane antigen I, Plasmodium