ArticleMalaria journal2021
Clinical recovery of Macaca fascicularis infected with Plasmodium knowlesi.
Article in Malaria journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Cage-Side Blood Collections from the Ear Can Be Used for Hematological Evaluations in Japanese Macaques (Macaca fuscata).Journal of the American Association for Laboratory Animal Science : JAALAS · 2026Article
- Plasmodium knowlesi Infection Is Associated With Elevated Circulating Biomarkers of Brain Injury and Endothelial Activation.The Journal of infectious diseases · 2025Article
- Animal Models of Malaria-Associated Acute Kidney Injury.Seminars in nephrology · 2025Review
- Characterizing the genetic diversity and population structure of Plasmodium knowlesi in Aceh Province, Indonesia.PloS one · 2025Article
- Proteomes of plasmodium knowlesi early and late ring-stage parasites and infected host erythrocytes.Journal of proteomics · 2024Article
- Plasmodium knowlesi in pig-tailed macaques: a potential new model for malaria vaccine research.Malaria journal · 2023Article
- No evidence of sustained nonzoonotic Plasmodium knowlesi transmission in Malaysia from modelling malaria case data.Nature communications · 2023Article
- Systems biology of malaria explored with nonhuman primates.Malaria journal · 2022Review
- Article
- Experimental Models to Study the Pathogenesis of Malaria-Associated Acute Respiratory Distress Syndrome.Frontiers in cellular and infection microbiology · 2022Review
- Dramatic transcriptomic differences in Macaca mulatta and Macaca fascicularis with Plasmodium knowlesi infections.Scientific reports · 2021Article
- Dynamic Control Balancing Cell Proliferation and Inflammation is Crucial for an Effective Immune Response to Malaria.Frontiers in molecular biosciences · 2021Article
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Authors and funding
26 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundKra 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.
methodsKra 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.
resultsAs 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.
conclusionsKra 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.
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