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This work was supported by Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (grant 71/2013 and Science Without Borders fellowships to M. A. M. B. and K. D.); Fundacao de Amparo a Pesquisa do Estado do Amazonas (grant PRONEM 009/2011, ProAM-Estado fellowship to B. B., and funding for M. V. G. L.'s laboratory); the Sao Paulo Research Foundation (B. W. H. and E. V. D. P.); CNPq (fellowships to W. M. M., E. V. D. P., and M. V. G. L. and funding for M. V. G. L.'s laboratory); the Brazilian Ministry of Health (funding for M. V. G. L.'s laboratory); and the Ministerio Espanol de Economia y Competitividad (grant SAF2016-80655-R to the laboratory of C. F. B. and H. A. d. P.).

Analysis of institutional authors

Baro BAuthorAyllon-Hermida AAuthorFernandez-Becerra CAuthorDel Portillo HaCorresponding Author

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August 4, 2021
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Article
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Morphological and Transcriptional Changes in Human Bone Marrow During Natural Plasmodium vivax Malaria Infections

Publicated to:Journal Of Infectious Diseases. 225 (7): 1274-1283 - 2022-04-01 225(7), DOI: 10.1093/infdis/jiaa177

Authors: Brito, MAM; Baro, B; Raiol, TC; Ayllon-Hermida, A; Safe, IP; Deroost, K; Figueiredo, EFG; Costa, AG; Armengol, MD; Sumoy, L; Almeida, ACG; Hounkpe, BW; De Paula, E; Fernandez-Becerra, C; Monteiro, WM; del Portillo, HA; Lacerda, MVG

Affiliations

Fiocruz MS, Inst Leonidas & Maria Deane, Manaus, Amazonas, Brazil - Author
Francis Crick Inst, London, England - Author
Fundacao Med Trop Dr Heiter Vieira Dourado, Manaus, Amazonas, Brazil - Author
Fundacao Oswaldo Cruz, Fiocruz Brasilia, Brasilia, DF, Brazil - Author
Hematol & Hemotherapy Fdn Amazonas State, Manaus, Amazonas, Brazil - Author
Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain - Author
Inst Invest Ciencies Salut Germans Trias & Pujol, Badalona, Spain - Author
Univ Barcelona, Hosp Clin, ISGlobal, Barcelona, Spain - Author
Univ Estado Amazonas, Manaus, Amazonas, Brazil - Author
Univ Estadual Campinas, Campinas, SP, Brazil - Author
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Abstract

Background The presence of Plasmodium vivax malaria parasites in the human bone marrow (BM) is still controversial. However, recent data from a clinical case and experimental infections in splenectomized nonhuman primates unequivocally demonstrated the presence of parasites in this tissue. Methods In the current study, we analyzed BM aspirates of 7 patients during the acute attack and 42 days after drug treatment. RNA extracted from CD71(+) cell suspensions was used for sequencing and transcriptomic analysis. Results We demonstrated the presence of parasites in all patients during acute infections. To provide further insights, we purified CD71(+) BM cells and demonstrated dyserythropoiesis and inefficient erythropoiesis in all patients. In addition, RNA sequencing from 3 patients showed that genes related to erythroid maturation were down-regulated during acute infections, whereas immune response genes were up-regulated. Conclusions This study thus shows that during P. vivax infections, parasites are always present in the BM and that such infections induced dyserythropoiesis and ineffective erythropoiesis. Moreover, infections induce transcriptional changes associated with such altered erythropoietic response, thus highlighting the importance of this hidden niche during natural infections.

Keywords

plasmodium vivaxanemiabloodbone marrow aspirateserythroblastserythropoiesisineffective erythropoiesisinhibitionmechanismsnatural infectionsrna sequencingAdultAnemiaAnimalsArticleAspirationBlood analysisBone marrowBone marrow aspiratesBone marrow biopsyBone marrow cellCd71 antigenCd71 geneCell maturationCell suspensionChloroquineClinical articleControlled studyCytokineCytometric bead arrayDown regulationDrug therapyDyserythropoiesisErythroid cellErythropoiesisFunctional enrichment analysisGeneGene expressionGene-expressionGenetic transcriptionHumanHuman cellHuman tissueHumansImmune response geneIneffective erythropoiesisInflammationMalaria, vivaxMicroscopyNatural infectionsPlasmodium vivaxPlasmodium vivax malariaPrimaquineQualitative analysisQuantitative analysisRnaRna extractionRna isolationRna sequencingTissue structureTranscriptomicsUpregulation

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Journal Of Infectious Diseases due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position 24/135, thus managing to position itself as a Q1 (Primer Cuartil), in the category Microbiology.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 3.41. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 2.5 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 9.58 (source consulted: Dimensions Aug 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-08-02, the following number of citations:

  • WoS: 31
  • Scopus: 32
  • Europe PMC: 21

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-08-02:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 62.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 68 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 12.85.
  • The number of mentions on the social network X (formerly Twitter): 7 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Brazil; United Kingdom.

the authors responsible for correspondence tasks have been Costa AG and del Portillo Obando, Hernando.