Clinical recovery of Macaca fascicularis infected with Plasmodium knowlesi

• Published in: Malaria Journal
• Main Authors: Mariko S. Peterson, Chester J. Joyner, Jessica A. Brady, Jennifer S. Wood, Monica Cabrera-Mora, Celia L. Saney, Luis L. Fonseca, Wayne T. Cheng, Jianlin Jiang, Stacey A. Lapp, Stephanie R. Soderberg, Mustafa V. Nural, Jay C. Humphrey, Allison Hankus, Deepa Machiah, Ebru Karpuzoglu, Jeremy D. DeBarry, MaHPIC-Consortium, Rabindra Tirouvanziam, Jessica C. Kissinger, Alberto Moreno, Sanjeev Gumber, Eberhard O. Voit, Juan B. Gutiérrez, Regina Joice Cordy, Mary R. Galinski
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2021
• Subjects: Malaria; Nonhuman primate models; Cynomolgus monkeys; Infectious diseases resilience; Telemetry; Fever; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/s12936-021-03925-6; https://doaj.org/article/164453a891c847b98c0ba2b111d57ed5

Abstract 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 ...