Malaria diagnostic methods - 'where to use what'
Discovery of automated haematology analysers for malaria diagnosis
First author, year and country | Number of participants and diagnoses | Index test criterion¶ | Sensitivity % | Specificity % |
---|---|---|---|---|
Mendelow, 1999, South Africa [18] | Total: 224 directed samples from 175 patients, P. falciparum: 93, Species not specified: 2 | CD** 3500 ≥1 depolarizing events‡ | 72 | 96 |
Hänscheid, 2001, Portugal† [39] | Total: 174, P. falciparum: 48, P. vivax: 6, P. ovale: 1, P. malariae: 2 | CD 3500 ≥2 depolarizing events | 95 | 88 |
Wever, 2002, The Netherlands† [36] | Total: 113, P. falciparum: 46, P. vivax: 5, P. ovale: 4, no differentiation for P. vivax or P. ovale: 3 | CD 3500 Either ≥1 depolarizing events or pseudoreticulocytosis | 62 | 96 |
Grobusch, 2003, Germany† [27] | Total: 403, P. falciparum: 87, P. vivax: 13, P. ovale: 5, P. malariae: 2 | CD 3000 ≥1 depolarizing events | 48.6 | 96.2 |
Scott, 2003, South Africa [35] | Total: 831, P. falciparum: 334, P. vivax: 7, P. ovale: 1, P. malariae: 2, mixed or unspecified: 6 | CD 4000 ≥1 depolarizing events | 80.2 | 87.3 |
Suh, 2003, South Korea [32] | Total: 168, P. vivax: 68 | CD 4000 ≥1 depolarizing events | 91.2 | 100 |
Dromigny, 2005, Senegal [30] | Total: 799 (directed: suspected of malaria 123, non-suspected random samples 676) P. falciparum: 68, treated or subclinical: 83 | CD 3200 ≥1 depolarizing events | Directed 92.9 Random 90.2 | Directed 93.8 Random 96.7 |
Padial, 2005, Equatorial Guinea [41] | Total: 411, P. falciparum: 35 , P. ovale: 3, mixed: 1 | CD 4000 | 72 | 98 |
Josephine, 2005, Malaysia [40] | Total: 889, P. vivax: 12, P. malariae: 3, P. falciparum: 1 | CD 4000 | 100 | 100 |
de Langen, 2006, Namibia [42] | Total: 208, P. falciparum: 90 | CD 3700 ≥1 depolarizing events | 93 | 97 |
Hänscheid, 2008, Gabon [34] | Children, total: 368, P. falciparum: 152 | CD 3000*** ≥1 depolarizing purple events Green-coded events | a) 96% b) 85% | a) 96% b) 96% |
Hänscheid, 2009, Gabon [43] | Pregnant patients, total 685, P. falciparum: 86 | CD 3000 ≥1 depolarizing events | 86.8 | 78.5 |
Rathod, 2009, India [33] | Total: 523, P. falciparum :73, P. vivax: 62 | CD 3200 ≥1 depolarizing events | 62.2 | 25.3 |
Cell-Dyn analysers and detection of malaria pigment (haemozoin)
Cell-Dyn analysers - colour code for events and cells detected
Purple dots. Depolarizing monocytes
Green dots. Granulocytes miss-classified as eosinophils
Blue dots. Abnormal lymphocytes or small monocytes?
Red dots and black dots. Haemozoin-containing parasites?
Cell-Dyn analysers and haemozoin-containing WBCs - studies on diagnostic accuracy
Cell-Dyn analysers - further malaria-related changes
Cell-Dyn analysers - changes observed in P. vivax and other species
Cell-Dyn analysers and malaria detection - limitations and necessary improvements
Cell type | Mean cell count in CBC result | Mean number of cells analysed | Mean number pixels on screen* | Information (cell count) lost in scatter-plot display (%)** |
---|---|---|---|---|
WBCs | 8675/μL | 9100 | 482 | 94.4 |
Granulocytes | 3834/μL | 4174 | 348 | 90.9 |
Lymphocytes | 2992/μL | 3068 | 22 | 99.3 |
Monocytes | 1334/μL | 1379 | 58 | 95.7 |
Eosinophils | 349/μL | 345 | 43 | 87.7 |
Coulter GEN·S and LH analysers
First author, year and country | Number of participants and diagnoses | Standard reference test | Blinding | Malaria factor | Sensitivity % | Specificity % |
---|---|---|---|---|---|---|
Fourcade, 2004, France and Spain [49] | Total: 89, P. falciparum: 28, P. vivax: 4 | Microscopy, HRP2+ pan-malarial antigen (Binax Now) | - | 5.1 | 82.5 | 96.9 |
Briggs, 2006, South Africa and England [48] | Total: 1354, healthy: 1079, febrile: 135, HIV infected: 51, P. falciparum: 120, P. vivax: 11, P. ovale: 7, P. malariae: 1, mixed P. falciparum and P. vivax: 1 | Microscopy, QBC, HRP2+ pan-malarial antigen (Binax Now), Pf HRP2 (MAKROmed), P-LDH (optiMAL) | - | 3.7 | 98 | 94 |
Kang, 2008, South Korea [66]* | Total: 395, P. vivax: 68 | Microscopy | ** | 4.57 | 81.8 | 72.3 |
Sysmex XE-2100 analyser
Abnormal DIFF, WBC/BASO and RET-EXT scatter-plots, and pseudoeosinophilia
First author, year and country | Number of participants and diagnoses | Blinding | Index test criterion | Sensitivity % | Specificity % | |
---|---|---|---|---|---|---|
Huh, 2008, South Korea [54] | Total: 463, P. vivax: 144 | - | >5% pseudoeosinophilia and/or an abnormal DIFF scatter-plot† | 69.4 | 100 | |
Yoo, 2010, South Korea [55]* | Total: 1801, P. vivax: 413 | - | 46.2 | 99.7 | ||
Campuzano-Zuluaga, 2010, Colombia [51] | Total: 158, P. falciparum: 30, P. vivax: 65, 63 febrile patients Validation control group including healthy and febrile participants: 161 | + |
Model
¶
|
Variables (Figure 4)
| ||
U-OD
Pv
‡ | 'XE-2100 P. vivax pattern' | 96.9 | 93.6 | |||
M-OD
Pv
** | Number of granulocyte DIFF abnormalities ≥7 pixels in the WBC/BASO(III) | 95.4 | 98.4 | |||
N-OD1
Pv
| ΔDIFF/WBC Plateletcrit LYMPH-Y | 94.3 | 95.1 | |||
N-OD2
Pv
| PLT-O Pixels WBC/BASO(III) | 96.8 | 96.8 | |||
N-OD1
Pf
| PLT-O RDW-SD LYMPH-Y | 93 | 81 | |||
N-OD2
Pf
| PLT-O RDW-SD Pixels WBC/BASO(III) | 86 | 90 |