Clinical recovery of Macaca fascicularis infected with Plasmodium knowlesi.

Autor: Peterson MS; Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.; Emory Vaccine Center, Emory University, Atlanta, GA, USA.; Emory University School of Medicine, Atlanta, GA, USA., Joyner CJ; Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.; Emory Vaccine Center, Emory University, Atlanta, GA, USA.; Center for Vaccines and Immunology, Department of Infectious Diseases, University of Georgia, Athens, GA, USA.; Center for Vaccines and Immunology, Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA., Brady JA; School of Chemical, Materials and Biomedical Engineering, University of Georgia, Athens, GA, USA.; Eli Lilly and Company, Indianapolis, IN, USA., Wood JS; Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA., Cabrera-Mora M; Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.; Emory Vaccine Center, Emory University, Atlanta, GA, USA.; College of Veterinary Medicine, University of Georgia, Athens, GA, USA., Saney CL; Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.; Emory Vaccine Center, Emory University, Atlanta, GA, USA., Fonseca LL; The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.; Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA., Cheng WT; Center for Vaccines and Immunology, Department of Infectious Diseases, University of Georgia, Athens, GA, USA., Jiang J; Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.; Emory Vaccine Center, Emory University, Atlanta, GA, USA., Lapp SA; Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.; Emory Vaccine Center, Emory University, Atlanta, GA, USA., Soderberg SR; Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.; Emory Vaccine Center, Emory University, Atlanta, GA, USA.; Thermo Fisher Scientific, South San Francisco, CA, USA., Nural MV; Institute of Bioinformatics, University of Georgia, Athens, GA, USA., Humphrey JC; Institute of Bioinformatics, University of Georgia, Athens, GA, USA.; Center for Tropical & Emerging Global Diseases, University of Georgia, Athens, GA, USA., Hankus A; Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.; Emory Vaccine Center, Emory University, Atlanta, GA, USA.; The MITRE Corporation, Atlanta, GA, USA., Machiah D; Division of Pathology, Yerkes National Primate Research Center, Atlanta, GA, USA., Karpuzoglu E; Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.; Emory Vaccine Center, Emory University, Atlanta, GA, USA.; Department of Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, GA, USA., DeBarry JD; Institute of Bioinformatics, University of Georgia, Athens, GA, USA.; Center for Topical and Emerging Global Diseases, University of Georgia, Athens, GA, USA., Tirouvanziam R; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA., Kissinger JC; Institute of Bioinformatics, University of Georgia, Athens, GA, USA.; Department of Genetics, University of Georgia, Athens, GA, USA.; Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, USA., Moreno A; Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.; Emory Vaccine Center, Emory University, Atlanta, GA, USA.; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA., Gumber S; Division of Pathology, Yerkes National Primate Research Center, Atlanta, GA, USA.; Department of Pathology and Laboratory Medicine, Emory School of Medicine, Atlanta, GA, USA.; Pathology, Drug Safety, and DMPK, Boehringer Ingelheim Animal Health USA, Inc., Athens, GA, USA., Voit EO; The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA., Gutiérrez JB; Department of Mathematics, University of Georgia, Athens, GA, USA.; Department of Mathematics, University of Texas at San Antonio, San Antonio, TX, USA., Cordy RJ; Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.; Emory Vaccine Center, Emory University, Atlanta, GA, USA.; Department of Biology, Wake Forest University, Winston-Salem, NC, USA., Galinski MR; Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA. Mary.Galinski@emory.edu.; Emory Vaccine Center, Emory University, Atlanta, GA, USA. Mary.Galinski@emory.edu.; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA. Mary.Galinski@emory.edu.
Jazyk: angličtina
Zdroj: Malaria journal [Malar J] 2021 Dec 30; Vol. 20 (1), pp. 486. Date of Electronic Publication: 2021 Dec 30.
DOI: 10.1186/s12936-021-03925-6
Abstrakt: Background: Kra monkeys (Macaca fascicularis), a natural host of Plasmodium knowlesi, control parasitaemia caused by this parasite species and escape death without treatment. Knowledge of the disease progression and resilience in kra monkeys will aid the effective use of this species to study mechanisms of resilience to malaria. This longitudinal study aimed to define clinical, physiological and pathological changes in kra monkeys infected with P. knowlesi, which could explain their resilient phenotype.
Methods: Kra monkeys (n = 15, male, young adults) were infected intravenously with cryopreserved P. knowlesi sporozoites and the resulting parasitaemias were monitored daily. Complete blood counts, reticulocyte counts, blood chemistry and physiological telemetry data (n = 7) were acquired as described prior to infection to establish baseline values and then daily after inoculation for up to 50 days. Bone marrow aspirates, plasma samples, and 22 tissue samples were collected at specific time points to evaluate longitudinal clinical, physiological and pathological effects of P. knowlesi infections during acute and chronic infections.
Results: As expected, the kra monkeys controlled acute infections and remained with low-level, persistent parasitaemias without anti-malarial intervention. Unexpectedly, early in the infection, fevers developed, which ultimately returned to baseline, as well as mild to moderate thrombocytopenia, and moderate to severe anaemia. Mathematical modelling and the reticulocyte production index indicated that the anaemia was largely due to the removal of uninfected erythrocytes and not impaired production of erythrocytes. Mild tissue damage was observed, and tissue parasite load was associated with tissue damage even though parasite accumulation in the tissues was generally low.
Conclusions: Kra monkeys experimentally infected with P. knowlesi sporozoites presented with multiple clinical signs of malaria that varied in severity among individuals. Overall, the animals shared common mechanisms of resilience characterized by controlling parasitaemia 3-5 days after patency, and controlling fever, coupled with physiological and bone marrow responses to compensate for anaemia. Together, these responses likely minimized tissue damage while supporting the establishment of chronic infections, which may be important for transmission in natural endemic settings. These results provide new foundational insights into malaria pathogenesis and resilience in kra monkeys, which may improve understanding of human infections.
(© 2021. The Author(s).)
Databáze: MEDLINE
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