Procalcitonin as a Candidate Biomarker for Malarial Infection and Severe Malaria: A Meta-Analysis
Abstract
:1. Background
2. Methods
2.1. Protocol and Registration
2.2. Eligibility Criteria
2.3. Information Sources and Searches
2.4. Study Screening and Selection
2.5. Data Extraction
2.6. Assessment of Risk of Bias
2.7. Data Synthesis and Statistical Analysis
3. Results
3.1. Search Results
3.2. Characteristics of the Included Studies
3.3. Risk of Bias among the Included Studies
3.4. Mean PCT Levels in Patients with Uncomplicated and Severe Malaria
3.5. Differences in PCT Levels between Severe and Uncomplicated Malaria
3.6. Differences in Mean PCT Levels between Uncomplicated Malaria, Asymptomatic Malaria, and Healthy Controls
3.7. Other Information on PCT Levels in Patients with Malaria
3.8. Sensitivity Analysis
3.9. Publication Bias
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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No. | Reference Study | Study Design | Study Location | Year | Characteristics of Participants | Number of Participants | Plasmodium Spp. | Mean Age (Years or Months) | Age Groups | Male Percentage | Procalcitonin (Mean ± SD or Median, Range) (ng/mL) | Parasite Density (Per Microliter) | Method for Malaria Detections | Method for Procalcitonin |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | Braun et al., 2003 [28] | Case-control study | Ghana | NS | Severe malaria (18), Uncomplicated malaria (18), Asymptomatic malaria (21), Healthy controls (13) | 70 | P. falciparum | Severe malaria (18): mean 20.9 months (95%CI 6.6–35.2), Uncomplicated malaria (18): 44.2 (32.2–56.3), Asymptomatic malaria (21): 67.3 (55.5–79.1), Healthy controls (13): 77.5 (58.2–96.9) | Children | NS | Severe malaria (18): 18.77 ± 11.60, Uncomplicated malaria (18): 25.27 ± 14.55, Asymptomatic malaria (21): 0.42 ± 0.27, Healthy controls (13): 0.64 ± 0.32 | Severe malaria (18): mean 17,150 (5394–28,910), Uncomplicated malaria (18): 70,320 (36,380–104,300), Asymptomatic malaria (21): 1709 (1136–2282) | Microscopy | LUMI-Test (Brahms Hennigsdorf, Germany) |
2 | Bruneel et al., 2016 [30] | Cohort study | France | 2007–2010 | Severe malaria (155), Uncomplicated malaria (140) | 295 | P. falciparum | Severe malaria (155): 44.4 ± 14.0, Uncomplicated malaria (140): 39.3 ± 12.5 | Adults | Severe malaria (155): 67.1, Uncomplicated malaria (140): 71.4 | Severe malaria (155): 41.1 ± 115.2, Uncomplicated malaria (140): 5.6 ± 11.2 | Severe malaria (155): 8.0% (3.3–15.0), Uncomplicated malaria (140): 0.5% (0.1–2.3) | Microscopy | PCT sensitive Kryptor Analyzer (Brahms, Hennigsdorf, Germany) |
3 | Chiwakata et al., 2001 [33] | Prospective observational study | Germany | NS | Severe malaria (25), Uncomplicated malaria (36) | 61 | P. falciparum | NS | NS | NS | Severe malaria (25): 10.67 (2.61–132.1), Uncomplicated malaria (36): 1.52 (0.5–5.6) | NS | Microscopy | Immunoluminometric assay (LUMItest PCT, (BRAHMS Diagnostica)) |
4 | Erdman et al., 2011 [37] | Case-control study | Uganda | 2007–2009 | Uncomplicated malaria (53), Cerebral malaria (44), Severe malarial anemia (59) | 156 | P. falciparum | Uncomplicated malaria (53): 4.4 (2.1–8.1), Cerebral malaria (44): 3.0 (1.5–4.3), Severe malarial anemia (59): 1.3 (0.9–2.0) | 6 months and 12 years | Uncomplicated malaria (53): 54.7, Cerebral malaria (44): 47.7, Severe malarial anemia (59): 50.8 | PCT was elevated in children with severe malaria compared to uncomplicated malaria | Uncomplicated malaria (53): 38,600 (16,600–126,000), Cerebral malaria (44): 98,600 (15,600–276,000), Severe malarial anemia (59): 266,00 (7460–126,000) | Microscopy | ELISAs (Ray BioTech) |
5 | Hesselink et al., 2009 [39] | Prospective observational study | Netherlands | NS | Severe falciparum malaria (6), Uncomplicated falciparum malaria (65), Uncomplicated non-falciparum malaria (29) | 100 | P. falciparum and non-P. falciparum (P. vivax, P. ovale, P. malariae) | Severe falciparum malaria (6): 48 (29–55), Uncomplicated falciparum malaria (65): 36 (9–67), Uncomplicated non-falciparum malaria (29): 36 (15–62) | Adults | Severe falciparum malaria (6): 66.7, Uncomplicated falciparum malaria (65): 72.3, Uncomplicated non-falciparum malaria (29): 75.9 | Severe falciparum malaria (6): increased 6/6, Uncomplicated falciparum malaria (65): 42/65, Uncomplicated non-falciparum malaria (29): 25/29 | Severe falciparum malaria (6): 174,900 (80,500–567,000), Uncomplicated falciparum malaria (65): 3422 (23–385,000), Uncomplicated non-falciparum malaria (29): NS | Microscopy, RDT, QBC (Quantitative Buffy Coat) | BRAHMS PCT-Q® test (Brahms Diagnostics, Germany) |
6 | Hollenstein et al., 1998 [36] | Case-control study | Thailand | NS | Severe malaria (27) | 27 | P. falciparum | 24.8 ± 8.3 | 16–45 | 85.2 | 40 ng/mL (range 0.04–662), elevated 26/27 | 290,680 (533–1,147,040) | Microscopy | Immunoluminometric assay (LUMItest, PCT; Brahms Diagnostica GmbH, Berlin, Germany) |
7 | Huang et al., 2019 [34] | Retrospective study | Congo, Angola, Pakistan, African countries | 2014–2018 | Severe malaria (1), Uncomplicated malaria (21) | 22 | P. falciparum (19), P. vivax (2), P. ovale (1) | 27.2 ± 4.8 | 20–48 | 100 | 3.28 (0.95, 13.11), elevated 21/22 | NS | Microscopy and RDT | A Roche Cobas E601 automatic electrochemical luminescence analyzer and an auxiliary reagent (ElecsysBRAHMSprocalcitonin, RocheDiagnostics GmbH) |
8 | Lin et al., 2018 [31] | Retrospective study | China | 2007–2016 | Severe malaria (27): exchange transfusion (15), controls (12) | 27 | P. falciparum | Exchange transfusion (15): 47.8 ± 4.4, controls (12): 46.0 ± 5.8 | NS | NS | Exchange transfusion (15): 53.83 ± 29.41 | Exchange transfusion (15): 742,000 ± 518,000, controls (12): 587,000 ± 264,000 | NS | NS |
9 | Lubell et al., 2015 [38] | Retrospective study | Cambodia, Laos and, Thailand | NS | Uncomplicated malaria (125) | 125 | NS | NS | NS | NS | Procalcitonin levels were significantly higher in malaria infections as compared with viral infections | NS | NS | Enzyme-Linked Fluorescent Assay technique via the Mini-VIDAS platform (BioMérieux, 69,280 Marcy-l’Etoile, France) |
10 | Mbengue et al., 2011 [40] | Prospective observational study | Senegal | 2000–2003 | Cerebral malaria (98) | 98 | P. falciparum | NS | NS | NS | Mean PCT levels were elevated in patients with active infection, with a large range of values (0.1 to 280 nanog per mL) significantly higher on day 0 in fatal cases than in survival cases (53.6 vs. 27.3; p = 0.01). | NS | Microscopy and RDT | Double site sandwich immunoluminometric assay according to the manufacturer’s instructions (LUMI-test® PCT; Brahms Diagnostica Gmbh, Berlin, Germany) |
11 | Mohapatra et al., 2013 [41] | Prospective observational study | India | 2011–2012 | Severe malaria (41), Uncomplicated malaria (19) | 60 | P. falciparum | Severe malaria (41): 37.10 ± 13.238, Uncomplicated malaria (19): 37.84 ± 15.5 | Adults | Severe malaria (41): 56.1, Uncomplicated malaria (19): 63.2 | Severe malaria (41): increased 41/41, Uncomplicated malaria (19): 12/19 | Severe malaria (41): 8578.82 ± 214.56, Uncomplicated malaria (19): 4569.58 ± 178.9 | Microscopy | B·R·A·H·M·S PCT-Q (B·R·A·H·M·S, Aktiengesellschaft Neuendorfstrasse 25 D-16761 Hennigsdorf, Germany) |
12 | Prodjosoewojo et al., 2019 [32] | Cohort study | Indonesia | 2004–2016 | Patients with malaria (4) | 4 | NS | 25 (19.8–35) | NS | 75 | 34.2 (20.7–43) | NS | Microscopy | BRAHMS PCT, Elecsys and Cobas e 411 analyzers (Roche Diagnostics GmbH, US) |
13 | Righi et al., 2016 [29] | Prospective observational study | Italy | 2011–2013 | Severe malaria (9), Uncomplicated malaria (21) | 30 | P. falciparum | Severe malaria (9): 42 ± 13.2, Uncomplicated malaria (21): 41 ± 9.9 | Adults | Severe malaria (9): 89, Uncomplicated malaria (21): 81 | Severe malaria (9): 6.88 (4–9), Uncomplicated malaria (21): 0.38 (0.30–2.72) | Severe malaria (9): 6.25% (3.25–13), Uncomplicated malaria (21): 1% (0.3–1.5) | Microscopy | Automated immunofluorescent assays (B·R·A·H·M·S PCT sensitive KRYPTOR, Brahms Diagnostics, Germany) |
14 | Uzzan et al., 2006 [35] | Prospective observational study | France | NS | Severe malaria (3), Uncomplicated malaria (25) | 28 | P. falciparum | 37 ± 13 | Adults | 64.3 | Malaria (18): 3.0 ± 4.6, increased in 14/18 | NS | Microscopy | Immunoluminometric assay on antibody-coated tubes (Lumitestw PCT, BRAHMS Diagnostica GmbH, Berlin, Germany) |
15 | van Wolfswinkel et al., 2012 [16] | Cohort study | Netherlands | 1999–2010 | Severe falciparum malaria (25), Uncomplicated falciparum malaria (116), Uncomplicated non-falciparum malaria (63) | 204 | P. falciparum and non-P. falciparum (P. vivax, P. ovale, P. malariae) | Severe falciparum malaria (25): 44 (23–70), Uncomplicated falciparum malaria (116): 41 (11–69), Uncomplicated non-falciparum malaria (63): 38 (8–62) | Adults | Severe falciparum malaria (25): 60, Uncomplicated falciparum malaria (116): 79, Uncomplicated non-falciparum malaria (63): 70 | Severe falciparum malaria (25): 1.9 (0.9–42.3), Uncomplicated falciparum malaria (116): 0.6 (0.0–11.2), Uncomplicated non-falciparum malaria (63): 1.6 (0.0–42.6) | Severe falciparum malaria (25): 284,005 (39,600–1,380,600), Uncomplicated falciparum malaria (116): 22,657 (2–156,600), Uncomplicated non-falciparum malaria (63): NS | Microscopy, RDT, QBC (Quantitative Buffy Coat) | EIA test (VIDAS BRAHMS Procalcitonin, bioMérieux, Lyon, France) |
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Mahittikorn, A.; Kotepui, K.U.; Mala, W.; Wilairatana, P.; Kotepui, M. Procalcitonin as a Candidate Biomarker for Malarial Infection and Severe Malaria: A Meta-Analysis. Int. J. Environ. Res. Public Health 2022, 19, 11389. https://doi.org/10.3390/ijerph191811389
Mahittikorn A, Kotepui KU, Mala W, Wilairatana P, Kotepui M. Procalcitonin as a Candidate Biomarker for Malarial Infection and Severe Malaria: A Meta-Analysis. International Journal of Environmental Research and Public Health. 2022; 19(18):11389. https://doi.org/10.3390/ijerph191811389
Chicago/Turabian StyleMahittikorn, Aongart, Kwuntida Uthaisar Kotepui, Wanida Mala, Polrat Wilairatana, and Manas Kotepui. 2022. "Procalcitonin as a Candidate Biomarker for Malarial Infection and Severe Malaria: A Meta-Analysis" International Journal of Environmental Research and Public Health 19, no. 18: 11389. https://doi.org/10.3390/ijerph191811389