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Published in: Malaria Journal 1/2006

Open Access 01-12-2006 | Research

Thick blood film examination for Plasmodium falciparum malaria has reduced sensitivity and underestimates parasite density

Authors: Philip Bejon, Laura Andrews, Angela Hunt-Cooke, Frances Sanderson, Sarah C Gilbert, Adrian VS Hill

Published in: Malaria Journal | Issue 1/2006

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Abstract

Background

Thick blood films are routinely used to diagnose Plasmodium falciparum malaria. Here, they were used to diagnose volunteers exposed to experimental malaria challenge.

Methods

The frequency with which blood films were positive at given parasite densities measured by PCR were analysed. The poisson distribution was used to calculate the theoretical likelihood of diagnosis. Further in vitro studies used serial dilutions to prepare thick films from malaria cultures at known parasitaemia.

Results

Even in expert hands, thick blood films were considerably less sensitive than might have been expected from the parasite numbers measured by quantitative PCR. In vitro work showed that thick films prepared from malaria cultures at known parasitaemia consistently underestimated parasite densities.

Conclusion

It appears large numbers of parasites are lost during staining. This limits their sensitivity, and leads to erroneous estimates of parasite density.
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Literature
1.
go back to reference Trape JF: Rapid evaluation of malaria parasite density and standardization of thick smear examination for epidemiological investigations. Trans R Soc Trop Med Hyg. 1985, 79: 181-184. 10.1016/0035-9203(85)90329-3.CrossRefPubMed Trape JF: Rapid evaluation of malaria parasite density and standardization of thick smear examination for epidemiological investigations. Trans R Soc Trop Med Hyg. 1985, 79: 181-184. 10.1016/0035-9203(85)90329-3.CrossRefPubMed
2.
go back to reference Dunachie SJ, Walther M, Vuola JM, Webster DP, Keating SM, Berthoud T, Andrews L, Bejon P, Poulton I, Butcher G, Watkins K, Sinden RE, Leach A, Moris P, Tornieporth N, Schneider J, Dubovsky F, Tierney E, Williams J, Gray Heppner D, Gilbert SC, Cohen J, Hill AV: A clinical trial of prime-boost immunisation with the candidate malaria vaccines RTS,S/AS02A and MVA-CS. Vaccine. 2006, 24: 2850-2859. 10.1016/j.vaccine.2005.12.041.CrossRefPubMed Dunachie SJ, Walther M, Vuola JM, Webster DP, Keating SM, Berthoud T, Andrews L, Bejon P, Poulton I, Butcher G, Watkins K, Sinden RE, Leach A, Moris P, Tornieporth N, Schneider J, Dubovsky F, Tierney E, Williams J, Gray Heppner D, Gilbert SC, Cohen J, Hill AV: A clinical trial of prime-boost immunisation with the candidate malaria vaccines RTS,S/AS02A and MVA-CS. Vaccine. 2006, 24: 2850-2859. 10.1016/j.vaccine.2005.12.041.CrossRefPubMed
3.
go back to reference Webster DP, Dunachie S, Vuola JM, Berthoud T, Keating S, Laidlaw SM, McConkey SJ, Poulton I, Andrews L, Andersen RF, Bejon P, Butcher G, Sinden R, Skinner MA, Gilbert SC, Hill AV: Enhanced T cell-mediated protection against malaria in human challenges by using the recombinant poxviruses FP9 and modified vaccinia virus Ankara. Proc Natl Acad Sci U S A. 2005, 102: 4836-4841. 10.1073/pnas.0406381102.PubMedCentralCrossRefPubMed Webster DP, Dunachie S, Vuola JM, Berthoud T, Keating S, Laidlaw SM, McConkey SJ, Poulton I, Andrews L, Andersen RF, Bejon P, Butcher G, Sinden R, Skinner MA, Gilbert SC, Hill AV: Enhanced T cell-mediated protection against malaria in human challenges by using the recombinant poxviruses FP9 and modified vaccinia virus Ankara. Proc Natl Acad Sci U S A. 2005, 102: 4836-4841. 10.1073/pnas.0406381102.PubMedCentralCrossRefPubMed
4.
go back to reference McConkey S RW: Enhanced T cell immunogenicity of plasmid DNA vaccines boosted by recombinant modified vaccinia virus Ankara in humans. Nature Medicine (2003) 9: 729-735. Nature Medicine. 2003, 9: 729-735. 10.1038/nm881.CrossRefPubMed McConkey S RW: Enhanced T cell immunogenicity of plasmid DNA vaccines boosted by recombinant modified vaccinia virus Ankara in humans. Nature Medicine (2003) 9: 729-735. Nature Medicine. 2003, 9: 729-735. 10.1038/nm881.CrossRefPubMed
5.
go back to reference Walther M, Dunachie S, Keating S, Vuola JM, Berthoud T, Schmidt A, Maier C, Andrews L, Andersen RF, Gilbert S, Poulton I, Webster D, Dubovsky F, Tierney E, Sarpotdar P, Correa S, Huntcooke A, Butcher G, Williams J, Sinden RE, Thornton GB, Hill AV: Safety, immunogenicity and efficacy of a pre-erythrocytic malaria candidate vaccine, ICC-1132 formulated in Seppic ISA 720. Vaccine. 2005, 23: 857-864. 10.1016/j.vaccine.2004.08.020.CrossRefPubMed Walther M, Dunachie S, Keating S, Vuola JM, Berthoud T, Schmidt A, Maier C, Andrews L, Andersen RF, Gilbert S, Poulton I, Webster D, Dubovsky F, Tierney E, Sarpotdar P, Correa S, Huntcooke A, Butcher G, Williams J, Sinden RE, Thornton GB, Hill AV: Safety, immunogenicity and efficacy of a pre-erythrocytic malaria candidate vaccine, ICC-1132 formulated in Seppic ISA 720. Vaccine. 2005, 23: 857-864. 10.1016/j.vaccine.2004.08.020.CrossRefPubMed
6.
go back to reference Andrews L, Andersen RF, Webster D, Dunachie S, Walther RM, Bejon P, Hunt-Cooke A, Bergson G, Sanderson F, Hill AV, Gilbert SC: Quantitative real-time polymerase chain reaction for malaria diagnosis and its use in malaria vaccine clinical trials. Am J Trop Med Hyg. 2005, 73: 191-198.PubMed Andrews L, Andersen RF, Webster D, Dunachie S, Walther RM, Bejon P, Hunt-Cooke A, Bergson G, Sanderson F, Hill AV, Gilbert SC: Quantitative real-time polymerase chain reaction for malaria diagnosis and its use in malaria vaccine clinical trials. Am J Trop Med Hyg. 2005, 73: 191-198.PubMed
7.
go back to reference Greenwood BM, Armstrong JR: Comparison of two simple methods for determining malaria parasite density. Trans R Soc Trop Med Hyg. 1991, 85: 186-188. 10.1016/0035-9203(91)90015-Q.CrossRefPubMed Greenwood BM, Armstrong JR: Comparison of two simple methods for determining malaria parasite density. Trans R Soc Trop Med Hyg. 1991, 85: 186-188. 10.1016/0035-9203(91)90015-Q.CrossRefPubMed
9.
go back to reference Dowling MA, Shute GT: A comparative study of thick and thin blood films in the diagnosis of scanty malaria parasitaemia. Bull World Health Organ. 1966, 34: 249-267.PubMedCentralPubMed Dowling MA, Shute GT: A comparative study of thick and thin blood films in the diagnosis of scanty malaria parasitaemia. Bull World Health Organ. 1966, 34: 249-267.PubMedCentralPubMed
11.
go back to reference Planche T, Krishna S, Kombila M, Engel K, Faucher JF, Ngou-Milama E, Kremsner PG: Comparison of methods for the rapid laboratory assessment of children with malaria. Am J Trop Med Hyg. 2001, 65: 599-602.PubMed Planche T, Krishna S, Kombila M, Engel K, Faucher JF, Ngou-Milama E, Kremsner PG: Comparison of methods for the rapid laboratory assessment of children with malaria. Am J Trop Med Hyg. 2001, 65: 599-602.PubMed
12.
go back to reference Armstrong Schellenberg JR: What is clinical Malaria? Finding case definitions for field research in highly endemic areas. Parasitology Today. 1994, 10: 439-441. 10.1016/0169-4758(94)90179-1.CrossRef Armstrong Schellenberg JR: What is clinical Malaria? Finding case definitions for field research in highly endemic areas. Parasitology Today. 1994, 10: 439-441. 10.1016/0169-4758(94)90179-1.CrossRef
13.
go back to reference Mwangi TW, Ross A, Snow RW, Marsh K: Case definitions of clinical malaria under different transmission conditions in Kilifi District, Kenya. J Infect Dis. 2005, 191: 1932-1939. 10.1086/430006.PubMedCentralCrossRefPubMed Mwangi TW, Ross A, Snow RW, Marsh K: Case definitions of clinical malaria under different transmission conditions in Kilifi District, Kenya. J Infect Dis. 2005, 191: 1932-1939. 10.1086/430006.PubMedCentralCrossRefPubMed
Metadata
Title
Thick blood film examination for Plasmodium falciparum malaria has reduced sensitivity and underestimates parasite density
Authors
Philip Bejon
Laura Andrews
Angela Hunt-Cooke
Frances Sanderson
Sarah C Gilbert
Adrian VS Hill
Publication date
01-12-2006
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2006
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-5-104

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