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Haematological consequences of acute uncomplicated falciparum malaria: a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data

Rashid Mansoor 1 Robert Commons 1 Nicholas Douglas 1 Benjamin Abuaku 1 Jane Achan 1 Ishag Adam 1 George Adjei 1 Martin Adjuik 1 Bereket Alemayehu 1 Richard Allan 1 Elizabeth Allen 1 Anupkumar Anvikar 1 Emmanuel Arinaitwe 1 Elizabeth Ashley 1 Hazel Ashurst 1 Puji Asih 1 Nathan Bakyaita 1 Hubert Barennes 1 Karen Barnes 1 Leonardo Basco 1, 2 Quique Bassat 1 Elisabeth Baudin 1 David Bell 1 Delia Bethell 1 Anders Bjorkman 1 Caroline Boulton 1 Teun Bousema 1 Philippe Brasseur 1 Hasifa Bukirwa 1 Rebekah Burrow 1 Verena Carrara 1 Michel Cot 1 Umberto D’alessandro 1 Debashish Das 1 Sabyasachi Das 1 Timothy Davis 1 Meghna Desai 1 Abdoulaye Djimde 1 Arjen Dondorp 1 Grant Dorsey 1 Chris Drakeley 1 Stephan Duparc 1 Emmanuelle Espié 1 Jean-Francois Etard 1 Catherine Falade 1 Jean Francois Faucher 1 Scott Filler 1 Carole Fogg 1 Mark Fukuda 1 Oumar Gaye 1 Blaise Genton 1 Awab Ghulam Rahim 1 Julius Gilayeneh 1 Raquel Gonzalez 1 Rebecca Grais 1 Francesco Grandesso 1 Brian Greenwood 1 Anastasia Grivoyannis 1 Christoph Hatz 1 Eva Maria Hodel 1 Georgina Humphreys 1 Jimee Hwang 1 Deus Ishengoma 1 Elizabeth Juma 1 S. Patrick Kachur 1 Piet Kager 1 Erasmus Kamugisha 1 Moses Kamya 1 Corine Karema 1 Kassoum Kayentao 1 Adama Kazienga 1 Jean-René Kiechel 1 Poul-Erik Kofoed 1 Kwadwo Koram 1 Peter Kremsner 1 David Lalloo 1 Moses Laman 1 Sue Lee 1 Bertrand Lell 1 Amelia Maiga 1 Andreas Mårtensson 1 Mayfong Mayxay 1 Wilfred Mbacham 1 Rose Mcgready 1 Hervé Menan 1 Didier Ménard 1 Frank Mockenhaupt 1 Brioni Moore 1 Olaf Müller 1 Alain Nahum 1 Jean-Louis Ndiaye 1 Paul Newton 1 Billy Ngasala 1 Frederic Nikiema 1 Akindeh Nji 1 Harald Noedl 1 Francois Nosten 1 Bernhards Ogutu 1 Olusola Ojurongbe 1 Lyda Osorio 1 Jean-Bosco Ouédraogo 1 Seth Owusu-Agyei 1 Anil Pareek 1 Louis Penali 1 Patrice Piola 1 Mateusz Plucinski 1 Zul Premji 1 Michael Ramharter 1 Caitlin Richmond 1 Lars Rombo 1 Cally Roper 1 Philip Rosenthal 1 Sam Salman 1 Albert Same-Ekobo 1 Carol Sibley 1 Sodiomon Sirima 1 Frank Smithuis 1 Fabrice Somé 1 Sarah Staedke 1 Peter Starzengruber 1 Nathalie Strub-Wourgaft 1 Inge Sutanto 1 Todd Swarthout 1 Din Syafruddin 1 Ambrose Talisuna 1 Walter Taylor 1 Emmanuel Temu 1 Julie Thwing 1 Halidou Tinto 1 Emiliana Tjitra 1 Offianan Touré 1 T. Hien Tran 1 Johan Ursing 1 Innocent Valea 1 Giovanni Valentini 1 Michele van Vugt 1 Lorenz von Seidlein 1 Stephen Ward 1 Vincent Were 1 Nicholas White 1 Charles Woodrow 1 William yavo 1 Adoke yeka 1 Issaka Zongo 1 Julie Simpson 1 Philippe Guerin 1 Kasia Stepniewska 1 Ric Price 1 
Abstract : Abstract Background Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. Methods Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall ≥ 25% at day 3 and day 7. Results A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0–19.7 g/dL) in Africa, 11.6 g/dL (range 5.0–20.0 g/dL) in Asia and 12.3 g/dL (range 6.9–17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to ≥ 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.58, respectively) and delayed parasite clearance (AOR = 2.44 and AOR = 2.59, respectively). In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39–3.05], p < 0.001). Conclusions In patients with uncomplicated P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery.
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Submitted on : Wednesday, May 25, 2022 - 4:36:18 PM
Last modification on : Thursday, May 26, 2022 - 3:11:55 AM

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Rashid Mansoor, Robert Commons, Nicholas Douglas, Benjamin Abuaku, Jane Achan, et al.. Haematological consequences of acute uncomplicated falciparum malaria: a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data. BMC Medicine, BioMed Central, 2022, 20 (1), pp.85. ⟨10.1186/s12916-022-02265-9⟩. ⟨hal-03678953⟩

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