title: Rapid diagnostic tests for malaria at sites of varying transmission intensity in Uganda.
abstract: BACKGROUND
  In Africa, fever is often treated presumptively as malaria, resulting in misdiagnosis and the overuse of antimalarial drugs. Rapid diagnostic tests (RDTs) for malaria may allow improved fever management.
  
  
  METHODS
  We compared RDTs based on histidine-rich protein 2 (HRP2) and RDTs based on Plasmodium lactate dehydrogenase (pLDH) with expert microscopy and PCR-corrected microscopy for 7000 patients at sites of varying malaria transmission intensity across Uganda.
  
  
  RESULTS
  When all sites were considered, the sensitivity of the HRP2-based test was 97% when compared with microscopy and 98% when corrected by PCR; the sensitivity of the pLDH-based test was 88% when compared with microscopy and 77% when corrected by PCR. The specificity of the HRP2-based test was 71% when compared with microscopy and 88% when corrected by PCR; the specificity of the pLDH-based test was 92% when compared with microscopy and >98% when corrected by PCR. Based on Plasmodium falciparum PCR-corrected microscopy, the positive predictive value (PPV) of the HRP2-based test was high (93%) at all but the site with the lowest transmission rate; the pLDH-based test and expert microscopy offered excellent PPVs (98%) for all sites. The negative predictive value (NPV) of the HRP2-based test was consistently high (>97%); in contrast, the NPV for the pLDH-based test dropped significantly (from 98% to 66%) as transmission intensity increased, and the NPV for expert microscopy decreased significantly (99% to 54%) because of increasing failure to detect subpatent parasitemia.
  
  
  CONCLUSIONS
  Based on the high PPV and NPV, HRP2-based RDTs are likely to be the best diagnostic choice for areas with medium-to-high malaria transmission rates in Africa.
authors.affiliation: University of California, San Francisco, San Francisco, California, USA. hhopkins@medsfgh.ucsf.edu
authors.forename: Heidi
authors.initials: H
authors.lastname: Hopkins
authors.forename: Lisa
authors.initials: L
authors.lastname: Bebell
authors.forename: Wilson
authors.initials: W
authors.lastname: Kambale
authors.forename: Christian
authors.initials: C
authors.lastname: Dokomajilar
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.forename: Grant
authors.initials: G
authors.lastname: Dorsey
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000953:Antigens, Protozoan / Q000032:analysis* / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D019353:Endemic Diseases; D006801:Humans; D007223:Infant; D007770:L-Lactate Dehydrogenase / Q000032:analysis* / Q000097:blood; D016778:Malaria, Falciparum / Q000097:blood / Q000175:diagnosis* / Q000201:enzymology; D008853:Microscopy; D011237:Predictive Value of Tests; D015800:Protozoan Proteins / Q000032:analysis* / Q000097:blood; D011933:Reagent Kits, Diagnostic / Q000469:parasitology*; D014454:Uganda
chemical_list: D000953:Antigens, Protozoan; C514457:HRP-2 antigen, Plasmodium falciparum; D015800:Protozoan Proteins; D011933:Reagent Kits, Diagnostic; D007770:L-Lactate Dehydrogenase