August 25, 2023
“Splenic reservoirs of Plasmodium vivax” with Dr Steven Kho
A very large biomass of intact asexual-stage malaria parasites accumulates in the spleen of asymptomatic human individuals infected with Plasmodium vivax. The mechanisms underlying this intense tropism are not clear. We hypothesised that immature reticulocytes, in which P. vivax develops, may display high densities in the spleen, thereby providing a niche for parasite survival. We examined spleen tissue in mostly ntreated individuals naturally exposed to P. vivax and Plasmodium falciparum undergoing splenectomy for any clinical indication in malaria-endemic Papua, Indonesia. Infection, parasite and immature reticulocyte density, and splenic distribution were analysed by optical microscopy, flow cytometry, and molecular assays. In Indonesia, 95.5% (21/22) of splenectomy patients had asymptomatic splenic Plasmodium infection (7 P. vivax, 13 P. falciparum, and 1 mixed infection). Significant splenic accumulation of immature CD71 intermediate- and high-expressing reticulocytes was seen, with concentrations 11 times greater than in peripheral blood. Asexual-stage P. vivax-infected erythrocytes of all developmental stages accumulated in the spleen, with non-phagocytosed parasite densities 3,590 times (IQR: 2,600 to 4,130) higher than in circulating blood, and with the splenic load accounting for 98.7% (IQR: 95.1% to 98.9%) of the estimated total-body P. vivax biomass. Taken together, significant accumulation and colocalization of asexual-stage P. vivax and immature reticulocytes in the cords and sinus lumens of the red pulp suggest the presence of an endosplenic lifecycle in P. vivax infections.
“Characterisation of Plasmodium vivax lactate dehydrogenase dynamics in P.vivax infections” with Pengxing Cao
Plasmodium vivax lactate dehydrogenase (PvLDH) is an essential enzyme in the glycolytic pathway of P. vivax. It is widely used as a diagnostic biomarker and a measure of total-body parasite biomass in vivax malaria. However, the dynamics of PvLDH remains poorly understood. Here, we developed mathematical models that capture parasite and matrix PvLDH dynamics in ex vivo culture and the human host. We estimated key biological parameters using ex vivo and in vivo longitudinal data of parasitemia and PvLDH concentration collected from P. vivax-infected humans using Bayesian hierarchical inference. We found that the ex vivo and in vivo estimates of intraerythrocytic PvLDH differed significantly across the asexual life cycle. The median in vivo estimate of intraerythrocytic PvLDH mass at the end of the life cycle was 9.4×10-3 ng, more than 15-fold higher than the ex vivo estimate of 5.1×10-4 ng. The median estimate of in vivo PvLDH half-life of 21.9 h was approximately three times shorter than the median estimate of ex vivo PvLDH half-life of 65.3 h. Our findings provide a foundation with which to advance our quantitative understanding of P. vivax biology and will facilitate the improvement of PvLDH-based diagnostic tools.