Haematological response in experimental human Plasmodium falciparum and Plasmodium vivax malaria

• Published in: Malaria journal 2021-12, Vol.20 (1), p.470-470, Article 470
• Main Authors: Woolley, Stephen D, Marquart, Louise, Woodford, John, Chalon, Stephan, Moehrle, Joerg J, McCarthy, James S, Barber, Bridget E
• Format: Article
• Language: English
• Subjects: Adult; Anaemia; Anemia; Anemia - drug therapy; Anemia - parasitology; Antimalarials - therapeutic use; Artemisinin; Blood; CHMI; Complications and side effects; COVID-19; Erythrocytes; Erythrocytes - parasitology; Female; Health aspects; Hematology; Hemoglobin; Human diseases; Humans; Induced blood-stage malaria; Infections; Inoculation; Malaria; Malaria, Falciparum - complications; Malaria, Falciparum - drug therapy; Malaria, Falciparum - parasitology; Malaria, Vivax - complications; Malaria, Vivax - drug therapy; Malaria, Vivax - parasitology; Male; Middle Aged; Morbidity; Parasitemia - drug therapy; Parasitemia - parasitology; Parasites; Phlebotomy; Physiological aspects; Plasmodium falciparum; Plasmodium falciparum - drug effects; Plasmodium vivax; Plasmodium vivax - drug effects; Risk factors; Variance analysis; Vector-borne diseases; VIS; Young Adult
• ISSN: 1475-2875; 1475-2875
• DOI: 10.1186/s12936-021-04003-7

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