Haematological response in experimental human Plasmodium falciparum and Plasmodium vivax malaria.
Anaemia
CHMI
Induced blood-stage malaria
Malaria
Plasmodium falciparum
VIS
Journal
Malaria journal
ISSN: 1475-2875
Titre abrégé: Malar J
Pays: England
ID NLM: 101139802
Informations de publication
Date de publication:
20 Dec 2021
20 Dec 2021
Historique:
received:
15
09
2021
accepted:
01
12
2021
entrez:
21
12
2021
pubmed:
22
12
2021
medline:
5
1
2022
Statut:
epublish
Résumé
Malaria-associated anaemia, arising from symptomatic, asymptomatic and submicroscopic infections, is a significant cause of morbidity worldwide. Induced blood stage malaria volunteer infection studies (IBSM-VIS) provide a unique opportunity to evaluate the haematological response to early Plasmodium falciparum and Plasmodium vivax infection. This study was an analysis of the haemoglobin, red cell counts, and parasitaemia data from 315 participants enrolled in IBSM-VIS between 2012 and 2019, including 269 participants inoculated with the 3D7 strain of P. falciparum (Pf3D7), 15 with an artemisinin-resistant P. falciparum strain (PfK13) and 46 with P. vivax. Factors associated with the fractional fall in haemoglobin (Hb-FF) were evaluated, and the malaria-attributable erythrocyte loss after accounting for phlebotomy-related losses was estimated. The relative contribution of parasitized erythrocytes to the malaria-attributable erythrocyte loss was also estimated. The median peak parasitaemia prior to treatment was 10,277 parasites/ml (IQR 3566-27,815), 71,427 parasites/ml [IQR 33,236-180,213], and 34,840 parasites/ml (IQR 13,302-77,064) in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively. The median Hb-FF was 10.3% (IQR 7.8-13.3), 14.8% (IQR 11.8-15.9) and 11.7% (IQR 8.9-14.5) in those inoculated with Pf3D7, PfK13 and P. vivax, respectively, with the haemoglobin nadir occurring a median 12 (IQR 5-21), 15 (IQR 7-22), and 8 (IQR 7-15) days following inoculation. In participants inoculated with P. falciparum, recrudescence was associated with a greater Hb-FF, while in those with P. vivax, the Hb-FF was associated with a higher pre-treatment parasitaemia and later day of anti-malarial treatment. After accounting for phlebotomy-related blood losses, the estimated Hb-FF was 4.1% (IQR 3.1-5.3), 7.2% (IQR 5.8-7.8), and 4.9% (IQR 3.7-6.1) in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively. Parasitized erythrocytes were estimated to account for 0.015% (IQR 0.006-0.06), 0.128% (IQR 0.068-0.616) and 0.022% (IQR 0.008-0.082) of the malaria-attributable erythrocyte loss in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively. Early experimental P. falciparum and P. vivax infection resulted in a small but significant fall in haemoglobin despite parasitaemia only just at the level of microscopic detection. Loss of parasitized erythrocytes accounted for < 0.2% of the total malaria-attributable haemoglobin loss.
Sections du résumé
BACKGROUND
BACKGROUND
Malaria-associated anaemia, arising from symptomatic, asymptomatic and submicroscopic infections, is a significant cause of morbidity worldwide. Induced blood stage malaria volunteer infection studies (IBSM-VIS) provide a unique opportunity to evaluate the haematological response to early Plasmodium falciparum and Plasmodium vivax infection.
METHODS
METHODS
This study was an analysis of the haemoglobin, red cell counts, and parasitaemia data from 315 participants enrolled in IBSM-VIS between 2012 and 2019, including 269 participants inoculated with the 3D7 strain of P. falciparum (Pf3D7), 15 with an artemisinin-resistant P. falciparum strain (PfK13) and 46 with P. vivax. Factors associated with the fractional fall in haemoglobin (Hb-FF) were evaluated, and the malaria-attributable erythrocyte loss after accounting for phlebotomy-related losses was estimated. The relative contribution of parasitized erythrocytes to the malaria-attributable erythrocyte loss was also estimated.
RESULTS
RESULTS
The median peak parasitaemia prior to treatment was 10,277 parasites/ml (IQR 3566-27,815), 71,427 parasites/ml [IQR 33,236-180,213], and 34,840 parasites/ml (IQR 13,302-77,064) in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively. The median Hb-FF was 10.3% (IQR 7.8-13.3), 14.8% (IQR 11.8-15.9) and 11.7% (IQR 8.9-14.5) in those inoculated with Pf3D7, PfK13 and P. vivax, respectively, with the haemoglobin nadir occurring a median 12 (IQR 5-21), 15 (IQR 7-22), and 8 (IQR 7-15) days following inoculation. In participants inoculated with P. falciparum, recrudescence was associated with a greater Hb-FF, while in those with P. vivax, the Hb-FF was associated with a higher pre-treatment parasitaemia and later day of anti-malarial treatment. After accounting for phlebotomy-related blood losses, the estimated Hb-FF was 4.1% (IQR 3.1-5.3), 7.2% (IQR 5.8-7.8), and 4.9% (IQR 3.7-6.1) in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively. Parasitized erythrocytes were estimated to account for 0.015% (IQR 0.006-0.06), 0.128% (IQR 0.068-0.616) and 0.022% (IQR 0.008-0.082) of the malaria-attributable erythrocyte loss in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively.
CONCLUSION
CONCLUSIONS
Early experimental P. falciparum and P. vivax infection resulted in a small but significant fall in haemoglobin despite parasitaemia only just at the level of microscopic detection. Loss of parasitized erythrocytes accounted for < 0.2% of the total malaria-attributable haemoglobin loss.
Identifiants
pubmed: 34930260
doi: 10.1186/s12936-021-04003-7
pii: 10.1186/s12936-021-04003-7
pmc: PMC8685492
doi:
Substances chimiques
Antimalarials
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
470Informations de copyright
© 2021. The Author(s).
Références
J Immunol. 2006 Oct 15;177(8):5736-45
pubmed: 17015763
Antimicrob Agents Chemother. 2015 Jul;59(7):4249-59
pubmed: 25963983
Cytokine. 2020 Jan;125:154838
pubmed: 31525609
Lancet Infect Dis. 2020 Aug;20(8):964-975
pubmed: 32275867
Heliyon. 2021 May 04;7(5):e06899
pubmed: 34027150
J Clin Invest. 2020 Jun 1;130(6):2920-2927
pubmed: 32045385
JCI Insight. 2018 Nov 15;3(22):
pubmed: 30429373
Blood. 2006 Oct 15;108(8):2569-77
pubmed: 16804108
Trans R Soc Trop Med Hyg. 1992 Nov-Dec;86(6):590-7
pubmed: 1287908
Infect Immun. 2017 Dec 19;86(1):
pubmed: 28923897
Int J Biol Sci. 2011;7(9):1427-42
pubmed: 22110393
J Infect Dis. 2019 Sep 26;220(9):1435-1443
pubmed: 31250022
Blood. 2014 Jul 10;124(2):167-75
pubmed: 24859359
PLoS One. 2009 Dec 24;4(12):e8446
pubmed: 20041181
Malar J. 2018 Oct 19;17(1):371
pubmed: 30340592
Clin Infect Dis. 2016 Jun 1;62(11):1403-1411
pubmed: 27107287
Nat Med. 2021 Apr;27(4):653-658
pubmed: 33619371
Am J Trop Med Hyg. 2020 May;102(5):1048-1055
pubmed: 32124722
PLoS Med. 2013 Dec;10(12):e1001575; discussion e1001575
pubmed: 24358031
Lancet Glob Health. 2020 Dec;8(12):e1499-e1511
pubmed: 33222799
BMC Infect Dis. 2017 Jun 23;17(1):443
pubmed: 28645255
Malar J. 2017 Aug 25;16(1):352
pubmed: 28841864
Sci Rep. 2017 Feb 08;7:41975
pubmed: 28176804
Acta Trop. 2009 Jan;109(1):55-60
pubmed: 18992209
Malar J. 2012 Jun 18;11:207
pubmed: 22709627
BMC Infect Dis. 2013 Mar 05;13:123
pubmed: 23497273
Bull World Health Organ. 2003;81(8):581-90
pubmed: 14576890
Clin Exp Immunol. 2003 Jun;132(3):467-72
pubmed: 12780694
J Infect Dis. 1993 Apr;167(4):932-7
pubmed: 8450258
Malar J. 2021 Apr 10;20(1):181
pubmed: 33838672
PLoS Med. 2021 May 26;18(5):e1003567
pubmed: 34038421
Clin Infect Dis. 2020 Dec 17;71(10):e657-e664
pubmed: 32239164
J Infect Dis. 2020 Mar 2;221(6):963-972
pubmed: 31679015
Trop Med Int Health. 2002 Oct;7(10):823-30
pubmed: 12358616
Am J Hematol. 2010 Apr;85(4):234-7
pubmed: 20196166
Antimicrob Agents Chemother. 2019 Dec 20;64(1):
pubmed: 31685476
Lancet Infect Dis. 2017 Jun;17(6):626-635
pubmed: 28363636
PLoS One. 2016 Oct 27;11(10):e0165340
pubmed: 27788243
Infect Immun. 2016 Aug 19;84(9):2689-96
pubmed: 27382019
PLoS Negl Trop Dis. 2016 Dec 8;10(12):e0005139
pubmed: 27930652
PLoS Med. 2020 Aug 21;17(8):e1003203
pubmed: 32822347
J Infect Dis. 2016 Jul 1;214(1):105-13
pubmed: 27056954
Br J Haematol. 2009 Jun;145(5):657-64
pubmed: 19344417
Malar J. 2012 May 24;11:173
pubmed: 22624872
mBio. 2015 Jan 20;6(1):
pubmed: 25604792
PLoS Med. 2021 May 26;18(5):e1003632
pubmed: 34038413
Malar J. 2021 Jan 14;20(1):43
pubmed: 33446191
J Clin Invest. 2018 Apr 2;128(4):1551-1562
pubmed: 29389671
Trans R Soc Trop Med Hyg. 1998 Sep-Oct;92(5):556-60
pubmed: 9861379
Am J Trop Med Hyg. 2001 Nov;65(5):614-22
pubmed: 11716124
PLoS Med. 2020 Oct 19;17(10):e1003359
pubmed: 33075101
Antimicrob Agents Chemother. 2020 Mar 24;64(4):
pubmed: 31932368
Clin Infect Dis. 2012 Apr;54(8):1080-90
pubmed: 22412067
Antimicrob Agents Chemother. 2021 Jan 20;65(2):
pubmed: 33199389
J Infect Dis. 2020 Jun 01;:
pubmed: 32479608
Br J Clin Pharmacol. 2013 Feb;75(2):524-37
pubmed: 22759078
Am J Trop Med Hyg. 2009 Dec;81(6):979-86
pubmed: 19996425
Parasitology. 1999 Aug;119 ( Pt 2):127-33
pubmed: 10466119
J Infect Dis. 2013 Nov 15;208(10):1688-94
pubmed: 23908484
PLoS One. 2015 Apr 20;10(4):e0123549
pubmed: 25893500
Antimicrob Agents Chemother. 2019 Mar 27;63(4):
pubmed: 30858218
Malar J. 2016 Sep 13;15:469
pubmed: 27624471
Haematologica. 2004 Apr;89(4):492-3
pubmed: 15075084
BMC Hematol. 2015 Oct 12;15:13
pubmed: 26464799
J Trop Pediatr. 2012 Apr;58(2):147-50
pubmed: 21602230
Am J Trop Med Hyg. 2003 Apr;68(4):410-2
pubmed: 12875288