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Published in: Malaria Journal 1/2010

Open Access 01-12-2010 | Research

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

Authors: Bruno B Andrade, Antonio Reis-Filho, Austeclino M Barros, Sebastião M Souza-Neto, Lucas L Nogueira, Kiyoshi F Fukutani, Erney P Camargo, Luís MA Camargo, Aldina Barral, Ângelo Duarte, Manoel Barral-Netto

Published in: Malaria Journal | Issue 1/2010

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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.
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Literature
2.
go back to reference Alexander N, Schellenberg D, Ngasala B, Petzold M, Drakeley C, Sutherland C: Assessing agreement between malaria slide density readings. Malar J. 2010, 9: 4-10.1186/1475-2875-9-4.PubMedCentralCrossRefPubMed Alexander N, Schellenberg D, Ngasala B, Petzold M, Drakeley C, Sutherland C: Assessing agreement between malaria slide density readings. Malar J. 2010, 9: 4-10.1186/1475-2875-9-4.PubMedCentralCrossRefPubMed
3.
go back to reference Bowers KM, Bell D, Chiodini PL, Barnwell J, Incardona S, Yen S, Luchavez J, Watt H: Inter-rater reliability of malaria parasite counts and comparison of methods. Malar J. 2009, 8: 267-10.1186/1475-2875-8-267.PubMedCentralCrossRefPubMed Bowers KM, Bell D, Chiodini PL, Barnwell J, Incardona S, Yen S, Luchavez J, Watt H: Inter-rater reliability of malaria parasite counts and comparison of methods. Malar J. 2009, 8: 267-10.1186/1475-2875-8-267.PubMedCentralCrossRefPubMed
4.
go back to reference Coleman RE, Maneechai N, Rachaphaew N, Kumpitak C, Miller RS, Soyseng V, Thimasarn K, Sattabongkot J: Comparison of field and expert laboratory microscopy for active surveillance for asymptomatic Plasmodium falciparum and Plasmodium vivax in western Thailand. Am J Trop Med Hyg. 2002, 67: 141-144.PubMed Coleman RE, Maneechai N, Rachaphaew N, Kumpitak C, Miller RS, Soyseng V, Thimasarn K, Sattabongkot J: Comparison of field and expert laboratory microscopy for active surveillance for asymptomatic Plasmodium falciparum and Plasmodium vivax in western Thailand. Am J Trop Med Hyg. 2002, 67: 141-144.PubMed
5.
go back to reference Khairnar K, Martin D, Lau R, Ralevski F, Pillai DR: Multiplex real-time quantitative PCR, microscopy and rapid diagnostic immuno-chromatographic tests for the detection of Plasmodium spp: performance, limit of detection analysis and quality assurance. Malar J. 2009, 8: 284-10.1186/1475-2875-8-284.PubMedCentralCrossRefPubMed Khairnar K, Martin D, Lau R, Ralevski F, Pillai DR: Multiplex real-time quantitative PCR, microscopy and rapid diagnostic immuno-chromatographic tests for the detection of Plasmodium spp: performance, limit of detection analysis and quality assurance. Malar J. 2009, 8: 284-10.1186/1475-2875-8-284.PubMedCentralCrossRefPubMed
6.
go back to reference Shokoples SE, Ndao M, Kowalewska-Grochowska K, Yanow SK: Multiplexed real-time PCR assay for discrimination of Plasmodium species with improved sensitivity for mixed infections. J Clin Microbiol. 2009, 47: 975-980. 10.1128/JCM.01858-08.PubMedCentralCrossRefPubMed Shokoples SE, Ndao M, Kowalewska-Grochowska K, Yanow SK: Multiplexed real-time PCR assay for discrimination of Plasmodium species with improved sensitivity for mixed infections. J Clin Microbiol. 2009, 47: 975-980. 10.1128/JCM.01858-08.PubMedCentralCrossRefPubMed
7.
go back to reference Murray CK, Gasser RA, Magill AJ, Miller RS: Update on rapid diagnostic testing for malaria. Clin Microbiol Rev. 2008, 21: 97-110. 10.1128/CMR.00035-07.PubMedCentralCrossRefPubMed Murray CK, Gasser RA, Magill AJ, Miller RS: Update on rapid diagnostic testing for malaria. Clin Microbiol Rev. 2008, 21: 97-110. 10.1128/CMR.00035-07.PubMedCentralCrossRefPubMed
8.
go back to reference Ashley EA, Touabi M, Ahrer M, Hutagalung R, Htun K, Luchavez J, Dureza C, Proux S, Leimanis M, Lwin MM, Koscalova A, Comte E, Hamade P, Page AL, Nosten F, Guerin PJ: Evaluation of three parasite lactate dehydrogenase-based rapid diagnostic tests for the diagnosis of falciparum and vivax malaria. Malar J. 2009, 8: 241-10.1186/1475-2875-8-241.PubMedCentralCrossRefPubMed Ashley EA, Touabi M, Ahrer M, Hutagalung R, Htun K, Luchavez J, Dureza C, Proux S, Leimanis M, Lwin MM, Koscalova A, Comte E, Hamade P, Page AL, Nosten F, Guerin PJ: Evaluation of three parasite lactate dehydrogenase-based rapid diagnostic tests for the diagnosis of falciparum and vivax malaria. Malar J. 2009, 8: 241-10.1186/1475-2875-8-241.PubMedCentralCrossRefPubMed
9.
go back to reference Coleman RE, Maneechai N, Ponlawat A, Kumpitak C, Rachapaew N, Miller RS, Sattabongkot J: Short report: Failure of the OptiMAL rapid malaria test as a tool for the detection of asymptomatic malaria in an area of Thailand endemic for Plasmodium falciparum and P. vivax. Am J Trop Med Hyg. 2002, 67: 563-565.PubMed Coleman RE, Maneechai N, Ponlawat A, Kumpitak C, Rachapaew N, Miller RS, Sattabongkot J: Short report: Failure of the OptiMAL rapid malaria test as a tool for the detection of asymptomatic malaria in an area of Thailand endemic for Plasmodium falciparum and P. vivax. Am J Trop Med Hyg. 2002, 67: 563-565.PubMed
10.
go back to reference da Silva J: National System in Health Surveillance: situation report: Rondônia. 2006, Brasília: Ministério da Saúde, 24- da Silva J: National System in Health Surveillance: situation report: Rondônia. 2006, Brasília: Ministério da Saúde, 24-
11.
go back to reference Alves FP, Durlacher RR, Menezes MJ, Krieger H, Silva LH, Camargo EP: High prevalence of asymptomatic Plasmodium vivax and Plasmodium falciparum infections in native Amazonian populations. Am J Trop Med Hyg. 2002, 66: 641-648.PubMed Alves FP, Durlacher RR, Menezes MJ, Krieger H, Silva LH, Camargo EP: High prevalence of asymptomatic Plasmodium vivax and Plasmodium falciparum infections in native Amazonian populations. Am J Trop Med Hyg. 2002, 66: 641-648.PubMed
12.
go back to reference Alves FP, Gil LH, Marrelli MT, Ribolla PE, Camargo EP, Da Silva LH: Asymptomatic carriers of Plasmodium spp. as infection source for malaria vector mosquitoes in the Brazilian Amazon. J Med Entomol. 2005, 42: 777-779. 10.1603/0022-2585(2005)042[0777:ACOPSA]2.0.CO;2.CrossRefPubMed Alves FP, Gil LH, Marrelli MT, Ribolla PE, Camargo EP, Da Silva LH: Asymptomatic carriers of Plasmodium spp. as infection source for malaria vector mosquitoes in the Brazilian Amazon. J Med Entomol. 2005, 42: 777-779. 10.1603/0022-2585(2005)042[0777:ACOPSA]2.0.CO;2.CrossRefPubMed
13.
go back to reference Rodrigues Ade F, Escobar AL, Souza-Santos R: Spatial analysis and determination of malaria control areas in the State of Rondonia. Rev Soc Bras Med Trop. 2008, 41: 55-64.CrossRefPubMed Rodrigues Ade F, Escobar AL, Souza-Santos R: Spatial analysis and determination of malaria control areas in the State of Rondonia. Rev Soc Bras Med Trop. 2008, 41: 55-64.CrossRefPubMed
14.
go back to reference Cavasini MT, Ribeiro WL, Kawamoto F, Ferreira MU: How prevalent is Plasmodium malariae in Rondonia, western Brazilian Amazon?. Rev Soc Bras Med Trop. 2000, 33: 489-492. 10.1590/S0037-86822000000500011.CrossRefPubMed Cavasini MT, Ribeiro WL, Kawamoto F, Ferreira MU: How prevalent is Plasmodium malariae in Rondonia, western Brazilian Amazon?. Rev Soc Bras Med Trop. 2000, 33: 489-492. 10.1590/S0037-86822000000500011.CrossRefPubMed
15.
go back to reference Andrade BB, Rocha BC, Reis-Filho A, Camargo LM, Tadei WP, Moreira LA, Barral A, Barral-Netto M: Anti-Anopheles darlingi saliva antibodies as marker of Plasmodium vivax infection and clinical immunity in the Brazilian Amazon. Malar J. 2009, 8: 121-10.1186/1475-2875-8-121.PubMedCentralCrossRefPubMed Andrade BB, Rocha BC, Reis-Filho A, Camargo LM, Tadei WP, Moreira LA, Barral A, Barral-Netto M: Anti-Anopheles darlingi saliva antibodies as marker of Plasmodium vivax infection and clinical immunity in the Brazilian Amazon. Malar J. 2009, 8: 121-10.1186/1475-2875-8-121.PubMedCentralCrossRefPubMed
16.
go back to reference Hagan MT, Demuth HB, Beale M: Neural networks design. 1996, Boston: PWS Publishing Co Hagan MT, Demuth HB, Beale M: Neural networks design. 1996, Boston: PWS Publishing Co
17.
go back to reference Pinkus A: Approximation theory of the MLP model in neural networks. Acta Numerica. 1999, 8: 143-195. 10.1017/S0962492900002919.CrossRef Pinkus A: Approximation theory of the MLP model in neural networks. Acta Numerica. 1999, 8: 143-195. 10.1017/S0962492900002919.CrossRef
18.
go back to reference Haykin S: Neural networks and learning machines. 2008, New Jersey: PrenticeHall, 3 Haykin S: Neural networks and learning machines. 2008, New Jersey: PrenticeHall, 3
19.
go back to reference Pattanasin S, Proux S, Chompasuk D, Luwiradaj K, Jacquier P, Looareesuwan S, Nosten F: Evaluation of a new Plasmodium lactate dehydrogenase assay (OptiMAL-IT) for the detection of malaria. Trans R Soc Trop Med Hyg. 2003, 97: 672-674. 10.1016/S0035-9203(03)80100-1.CrossRefPubMed Pattanasin S, Proux S, Chompasuk D, Luwiradaj K, Jacquier P, Looareesuwan S, Nosten F: Evaluation of a new Plasmodium lactate dehydrogenase assay (OptiMAL-IT) for the detection of malaria. Trans R Soc Trop Med Hyg. 2003, 97: 672-674. 10.1016/S0035-9203(03)80100-1.CrossRefPubMed
20.
21.
go back to reference Iqbal J, Khalid N, Hira PR: Comparison of two commercial assays with expert microscopy for confirmation of symptomatically diagnosed malaria. J Clin Microbiol. 2002, 40: 4675-4678. 10.1128/JCM.40.12.4675-4678.2002.PubMedCentralCrossRefPubMed Iqbal J, Khalid N, Hira PR: Comparison of two commercial assays with expert microscopy for confirmation of symptomatically diagnosed malaria. J Clin Microbiol. 2002, 40: 4675-4678. 10.1128/JCM.40.12.4675-4678.2002.PubMedCentralCrossRefPubMed
22.
go back to reference Valea I, Tinto H, Nikiema M, Yamuah L, Rouamba N, Drabo M, Guiguemde RT, d'Alessandro U: Performance of OptiMAL-IT compared to microscopy, for malaria detection in Burkina Faso. Trop Med Int Health. 2009, 14: 338-340. 10.1111/j.1365-3156.2009.02228.x.CrossRefPubMed Valea I, Tinto H, Nikiema M, Yamuah L, Rouamba N, Drabo M, Guiguemde RT, d'Alessandro U: Performance of OptiMAL-IT compared to microscopy, for malaria detection in Burkina Faso. Trop Med Int Health. 2009, 14: 338-340. 10.1111/j.1365-3156.2009.02228.x.CrossRefPubMed
23.
go back to reference Forney JR, Wongsrichanalai C, Magill AJ, Craig LG, Sirichaisinthop J, Bautista CT, Miller RS, Ockenhouse CF, Kester KE, Aronson NE, Andersen EM, Quino-Ascurra HA, Vidal C, Moran KA, Murray CK, DeWitt CC, Heppner DG, Kain KC, Ballou WR, Gasser RA: Devices for rapid diagnosis of Malaria: evaluation of prototype assays that detect Plasmodium falciparum histidine-rich protein 2 and a Plasmodium vivax-specific antigen. J Clin Microbiol. 2003, 41: 2358-2366. 10.1128/JCM.41.6.2358-2366.2003.PubMedCentralCrossRefPubMed Forney JR, Wongsrichanalai C, Magill AJ, Craig LG, Sirichaisinthop J, Bautista CT, Miller RS, Ockenhouse CF, Kester KE, Aronson NE, Andersen EM, Quino-Ascurra HA, Vidal C, Moran KA, Murray CK, DeWitt CC, Heppner DG, Kain KC, Ballou WR, Gasser RA: Devices for rapid diagnosis of Malaria: evaluation of prototype assays that detect Plasmodium falciparum histidine-rich protein 2 and a Plasmodium vivax-specific antigen. J Clin Microbiol. 2003, 41: 2358-2366. 10.1128/JCM.41.6.2358-2366.2003.PubMedCentralCrossRefPubMed
24.
go back to reference Gillet P, van Dijk DP, Bottieau E, Cnops L, Van Esbroeck M, Jacobs J: Test characteristics of the SD FK80 Plasmodium falciparum/Plasmodium vivax malaria rapid diagnostic test in a non-endemic setting. Malar J. 2009, 8: 262-10.1186/1475-2875-8-262.PubMedCentralCrossRefPubMed Gillet P, van Dijk DP, Bottieau E, Cnops L, Van Esbroeck M, Jacobs J: Test characteristics of the SD FK80 Plasmodium falciparum/Plasmodium vivax malaria rapid diagnostic test in a non-endemic setting. Malar J. 2009, 8: 262-10.1186/1475-2875-8-262.PubMedCentralCrossRefPubMed
25.
go back to reference Baliraine FN, Afrane YA, Amenya DA, Bonizzoni M, Menge DM, Zhou G, Zhong D, Vardo-Zalik AM, Githeko AK, Yan G: High prevalence of asymptomatic plasmodium falciparum infections in a highland area of western Kenya: a cohort study. J Infect Dis. 2009, 200: 66-74. 10.1086/599317.PubMedCentralCrossRefPubMed Baliraine FN, Afrane YA, Amenya DA, Bonizzoni M, Menge DM, Zhou G, Zhong D, Vardo-Zalik AM, Githeko AK, Yan G: High prevalence of asymptomatic plasmodium falciparum infections in a highland area of western Kenya: a cohort study. J Infect Dis. 2009, 200: 66-74. 10.1086/599317.PubMedCentralCrossRefPubMed
26.
go back to reference Marangi M, Di Tullio R, Mens PF, Martinelli D, Fazio V, Angarano G, Schallig HD, Giangaspero A, Scotto G: Prevalence of Plasmodium spp. in malaria asymptomatic African migrants assessed by nucleic acid sequence based amplification. Malar J. 2009, 8: 12-10.1186/1475-2875-8-12.PubMedCentralCrossRefPubMed Marangi M, Di Tullio R, Mens PF, Martinelli D, Fazio V, Angarano G, Schallig HD, Giangaspero A, Scotto G: Prevalence of Plasmodium spp. in malaria asymptomatic African migrants assessed by nucleic acid sequence based amplification. Malar J. 2009, 8: 12-10.1186/1475-2875-8-12.PubMedCentralCrossRefPubMed
27.
go back to reference da Silva-Nunes M, Ferreira MU: Clinical spectrum of uncomplicated malaria in semi-immune Amazonians: beyond the "symptomatic" vs "asymptomatic" dichotomy. Mem Inst Oswaldo Cruz. 2007, 102: 341-347.CrossRefPubMed da Silva-Nunes M, Ferreira MU: Clinical spectrum of uncomplicated malaria in semi-immune Amazonians: beyond the "symptomatic" vs "asymptomatic" dichotomy. Mem Inst Oswaldo Cruz. 2007, 102: 341-347.CrossRefPubMed
28.
go back to reference Coura JR, Suarez-Mutis M, Ladeia-Andrade S: A new challenge for malaria control in Brazil: asymptomatic Plasmodium infection--a review. Mem Inst Oswaldo Cruz. 2006, 101: 229-237.PubMed Coura JR, Suarez-Mutis M, Ladeia-Andrade S: A new challenge for malaria control in Brazil: asymptomatic Plasmodium infection--a review. Mem Inst Oswaldo Cruz. 2006, 101: 229-237.PubMed
29.
go back to reference Coleman RE, Sattabongkot J, Promstaporm S, Maneechai N, Tippayachai B, Kengluecha A, Rachapaew N, Zollner G, Miller RS, Vaughan JA, Thimasarn K, Khuntirat B: Comparison of PCR and microscopy for the detection of asymptomatic malaria in a Plasmodium falciparum/vivax endemic area in Thailand. Malar J. 2006, 5: 121-10.1186/1475-2875-5-121.PubMedCentralCrossRefPubMed Coleman RE, Sattabongkot J, Promstaporm S, Maneechai N, Tippayachai B, Kengluecha A, Rachapaew N, Zollner G, Miller RS, Vaughan JA, Thimasarn K, Khuntirat B: Comparison of PCR and microscopy for the detection of asymptomatic malaria in a Plasmodium falciparum/vivax endemic area in Thailand. Malar J. 2006, 5: 121-10.1186/1475-2875-5-121.PubMedCentralCrossRefPubMed
30.
go back to reference Metenou S, Dembele B, Konate S, Dolo H, Coulibaly SY, Coulibaly YI, Diallo AA, Soumaoro L, Coulibaly ME, Sanogo D, Doumbia SS, Wagner M, Traoré SF, Klion A, Mahanty S, Nutman TB: Patent filarial infection modulates malaria-specific type 1 cytokine responses in an IL-10-dependent manner in a filaria/malaria-coinfected population. J Immunol. 2009, 183: 916-924. 10.4049/jimmunol.0900257.PubMedCentralCrossRefPubMed Metenou S, Dembele B, Konate S, Dolo H, Coulibaly SY, Coulibaly YI, Diallo AA, Soumaoro L, Coulibaly ME, Sanogo D, Doumbia SS, Wagner M, Traoré SF, Klion A, Mahanty S, Nutman TB: Patent filarial infection modulates malaria-specific type 1 cytokine responses in an IL-10-dependent manner in a filaria/malaria-coinfected population. J Immunol. 2009, 183: 916-924. 10.4049/jimmunol.0900257.PubMedCentralCrossRefPubMed
Metadata
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
Authors
Bruno B Andrade
Antonio Reis-Filho
Austeclino M Barros
Sebastião M Souza-Neto
Lucas L Nogueira
Kiyoshi F Fukutani
Erney P Camargo
Luís MA Camargo
Aldina Barral
Ângelo Duarte
Manoel Barral-Netto
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2010
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-9-117

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