title: Towards a precise test for malaria diagnosis in the Brazilian Amazon: comparison among field microscopy, a rapid diagnostic test, nested PCR, and a computational expert system based on artificial neural networks.
abstract: BACKGROUND
  Accurate malaria diagnosis is mandatory for the treatment and management of severe cases. Moreover, individuals with asymptomatic malaria are not usually screened by health care facilities, which further complicates disease control efforts. The present study compared the performances of a malaria rapid diagnosis test (RDT), the thick blood smear method and nested PCR for the diagnosis of symptomatic malaria in the Brazilian Amazon. In addition, an innovative computational approach was tested for the diagnosis of asymptomatic malaria.
  
  
  METHODS
  The study was divided in two parts. For the first part, passive case detection was performed in 311 individuals with malaria-related symptoms from a recently urbanized community in the Brazilian Amazon. A cross-sectional investigation compared the diagnostic performance of the RDT Optimal-IT, nested PCR and light microscopy. The second part of the study involved active case detection of asymptomatic malaria in 380 individuals from riverine communities in Rondônia, Brazil. The performances of microscopy, nested PCR and an expert computational system based on artificial neural networks (MalDANN) using epidemiological data were compared.
  
  
  RESULTS
  Nested PCR was shown to be the gold standard for diagnosis of both symptomatic and asymptomatic malaria because it detected the major number of cases and presented the maximum specificity. Surprisingly, the RDT was superior to microscopy in the diagnosis of cases with low parasitaemia. Nevertheless, RDT could not discriminate the Plasmodium species in 12 cases of mixed infections (Plasmodium vivax + Plasmodium falciparum). Moreover, the microscopy presented low performance in the detection of asymptomatic cases (61.25% of correct diagnoses). The MalDANN system using epidemiological data was worse that the light microscopy (56% of correct diagnoses). However, when information regarding plasma levels of interleukin-10 and interferon-gamma were inputted, the MalDANN performance sensibly increased (80% correct diagnoses).
  
  
  CONCLUSIONS
  An RDT for malaria diagnosis may find a promising use in the Brazilian Amazon integrating a rational diagnostic approach. Despite the low performance of the MalDANN test using solely epidemiological data, an approach based on neural networks may be feasible in cases where simpler methods for discriminating individuals below and above threshold cytokine levels are available.
authors.affiliation: Centro de Pesquisas Gonçalo Moniz, OCRUZ, Bahia, Brazil.
authors.forename: Bruno B
authors.initials: BB
authors.lastname: Andrade
authors.forename: Antonio
authors.initials: A
authors.lastname: Reis-Filho
authors.forename: Austeclino M
authors.initials: AM
authors.lastname: Barros
authors.forename: Sebastião M
authors.initials: SM
authors.lastname: Souza-Neto
authors.forename: Lucas L
authors.initials: LL
authors.lastname: Nogueira
authors.forename: Kiyoshi F
authors.initials: KF
authors.lastname: Fukutani
authors.forename: Erney P
authors.initials: EP
authors.lastname: Camargo
authors.forename: Luís M A
authors.initials: LM
authors.lastname: Camargo
authors.forename: Aldina
authors.initials: A
authors.lastname: Barral
authors.forename: Angelo
authors.initials: A
authors.lastname: Duarte
authors.forename: Manoel
authors.initials: M
authors.lastname: Barral-Netto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001800:Blood Specimen Collection / Q000379:methods; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005103:Expert Systems; D005260:Female; D006801:Humans; D008288:Malaria / Q000175:diagnosis* / Q000469:parasitology; D008297:Male; D008853:Microscopy / Q000379:methods*; D008875:Middle Aged; D016571:Neural Networks, Computer; D018512:Parasitemia / Q000175:diagnosis / Q000453:epidemiology / Q000469:parasitology; D010961:Plasmodium / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction / Q000379:methods*; D012680:Sensitivity and Specificity; D055815:Young Adult
references.citation: J Clin Microbiol. 2002 Dec;40(12):4675-8
references.pmid: 12454171
references.citation: Nature. 2002 Feb 7;415(6872):670-2
references.pmid: 11832954
references.citation: Malar J. 2004 Nov 01;3:38
references.pmid: 15516269
references.citation: Malar J. 2010 Jan 04;9:4
references.pmid: 20047679
references.citation: Mem Inst Oswaldo Cruz. 2007 Jun;102(3):341-7
references.pmid: 17568940
references.citation: Malar J. 2009 Nov 22;8:262
references.pmid: 19930609
references.citation: J Infect Dis. 2009 Jul 1;200(1):66-74
references.pmid: 19476434
references.citation: J Immunol. 2009 Jul 15;183(2):916-24
references.pmid: 19561105
references.citation: Mem Inst Oswaldo Cruz. 2006 May;101(3):229-37
references.pmid: 16862314
references.citation: Rev Soc Bras Med Trop. 2000 Sep-Oct;33(5):489-92
references.pmid: 11064586
references.citation: J Clin Microbiol. 2003 Jun;41(6):2358-66
references.pmid: 12791849
references.citation: Malar J. 2009 Nov 25;8:267
references.pmid: 19939271
references.citation: J Med Entomol. 2005 Sep;42(5):777-9
references.pmid: 16363160
references.citation: Malar J. 2009 Jun 05;8:121
references.pmid: 19500362
references.citation: Malar J. 2006 Dec 14;5:121
references.pmid: 17169142
references.citation: Am J Trop Med Hyg. 2002 Aug;67(2):141-4
references.pmid: 12389937
references.citation: Am J Trop Med Hyg. 2002 Jun;66(6):641-8
references.pmid: 12224567
references.citation: Malar J. 2009 Jan 12;8:12
references.pmid: 19138412
references.citation: Malar J. 2009 Oct 27;8:241
references.pmid: 19860920
references.citation: Trans R Soc Trop Med Hyg. 2003 Nov-Dec;97(6):672-4
references.pmid: 16117960
references.citation: Clin Microbiol Rev. 2008 Jan;21(1):97-110
references.pmid: 18202438
references.citation: Malar J. 2009 Dec 09;8:284
references.pmid: 20003199
references.citation: Rev Soc Bras Med Trop. 2008 Jan-Feb;41(1):55-64
references.pmid: 18368272
references.citation: J Clin Microbiol. 2009 Apr;47(4):975-80
references.pmid: 19244467
references.citation: Am J Trop Med Hyg. 2002 Dec;67(6):563-5
references.pmid: 12518844
references.citation: Trop Med Int Health. 2009 Mar;14(3):338-40
references.pmid: 19187517