scholarly journals Total parasite biomass but not peripheral parasitaemia is associated with endothelial and haematological perturbations in Plasmodium vivax patients

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
João Luiz Silva-Filho ◽  
João CK Dos-Santos ◽  
Carla C Judice ◽  
Dario Beraldi ◽  
Kannan Venugopal ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Ex Vivo ◽  
Parasite Burden ◽  
Host Responses ◽  
Severe Thrombocytopenia ◽  
High Association ◽  
Healthy Donors ◽  
Circulating Markers ◽  
Patient Subgroups

Plasmodium vivax is the major cause of human malaria in the Americas. How P. vivax infection can lead to poor clinical outcomes, despite low peripheral parasitaemia remains a matter of intense debate. Estimation of total P. vivax biomass based on circulating markers indicates existence of a predominant parasite population outside of circulation. In this study we investigate associations between both peripheral and total parasite biomass and host response in vivax malaria. We analysed parasite and host signatures in a cohort of uncomplicated vivax malaria patients from Manaus, Brazil, combining clinical and parasite parameters, multiplexed analysis of host responses and ex vivo assays. Patterns of clinical features, parasite burden and host signatures measured in plasma across the patient cohort were highly heterogenous. Further data deconvolution revealed two patient clusters, here termed Vivaxlow and Vivaxhigh. These patient subgroups were defined based on differences in total parasite biomass but not peripheral parasitaemia. Overall Vivaxlow patients clustered with healthy donors and Vivaxhigh patients showed more profound alterations in haematological parameters, endothelial cell (EC) activation and glycocalyx breakdown and levels of cytokines regulating different haematopoiesis pathways compared to Vivaxlow. Vivaxhigh patients presented more severe thrombocytopenia and lymphopenia, along with enrichment of neutrophils in the peripheral blood and increased neutrophil-to-lymphocyte ratio (NLCR). When patients' signatures were combined, high association of total parasite biomass with a subset of markers of EC activation, thrombocytopenia and lymphopenia severity was observed. Finally, machine learning models defined a combination of host parameters measured in the circulation that could predict the extent of parasite infection outside of circulation. Altogether, our data show that total parasite biomass is a better predictor of perturbations in host homeostasis in P. vivax patients than peripheral parasitaemia. This supports the emerging paradigm of a P. vivax tissue reservoir, in particular in the hematopoietic niche of bone marrow and spleen.

scholarly journals Total parasite biomass but not peripheral parasitaemia is associated with endothelial and haematological perturbations in Plasmodium vivax patients

2021 ◽  
Author(s):  
João L Silva-Filho ◽  
João CK Dos-Santos ◽  
Carla Judice ◽  
Dario Beraldi ◽  
Kannan Venugopal ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Ex Vivo ◽  
Parasite Burden ◽  
Host Responses ◽  
Severe Thrombocytopenia ◽  
High Association ◽  
Healthy Donors ◽  
Circulating Markers ◽  
Patient Subgroups

AbstractPlasmodium vivax is the major cause of human malaria in the Americas. How P. vivax infection can lead to poor clinical outcomes, despite low peripheral parasitaemia remains a matter of intense debate. Estimation of total P. vivax biomass based on circulating markers indicates existence of a predominant parasite population outside of circulation. In this study we investigate associations between both peripheral and total parasite biomass and host response in vivax malaria. We analysed parasite and host signatures in a cohort of uncomplicated vivax malaria patients from Manaus, Brazil, combining clinical and parasite parameters, multiplexed analysis of host responses and ex vivo assays. Patterns of clinical features, parasite burden and host signatures measured in plasma across the patient cohort were highly heterogenous. Further data deconvolution revealed two patient clusters, here termed Vivaxlow and Vivaxhigh. These patient subgroups were defined based on differences in total parasite biomass but not peripheral parasitaemia. Overall Vivaxlow patients clustered with healthy donors and Vivaxhigh patients showed more profound alterations in haematological parameters, endothelial cell (EC) activation and glycocalyx breakdown and levels of cytokines regulating different haematopoiesis pathways compared to Vivaxlow. Vivaxhigh patients presented more severe thrombocytopenia and lymphopenia, along with enrichment of neutrophils in the peripheral blood and increased neutrophil-to-lymphocyte ratio (NLCR). When patients’ signatures were combined, high association of total parasite biomass with a subset of markers of EC activation, thrombocytopenia and lymphopenia severity was observed. Finally, machine learning models defined a combination of host parameters measured in the circulation that could predict the extent of parasite infection outside of circulation. Altogether, our data show that total parasite biomass is a better predictor of perturbations in host homeostasis in P. vivax patients than peripheral parasitaemia. This supports the emerging paradigm of a P. vivax tissue reservoir, in particular in the hematopoietic niche of bone marrow and spleen.

Childhood Plasmodium vivax Malaria With Severe Thrombocytopenia and Bleeding Manifestations

2009 ◽  
Vol 31 (10) ◽  
pp. 758-759 ◽  
Author(s):  
Rajoo Thapa ◽  
Biswajit Biswas ◽  
Debkrishna Mallick ◽  
Swarup Sardar ◽  
Sujoy Modak
Keyword(s):  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Severe Thrombocytopenia ◽  
Plasmodium Vivax Malaria

scholarly journals Monitoring the Efficacy of Chloroquine-Primaquine Therapy for Uncomplicated Plasmodium vivax Malaria in the Main Transmission Hot Spot of Brazil

2019 ◽  
Vol 63 (5) ◽  
Author(s):  
Simone Ladeia-Andrade ◽  
Maria José Menezes ◽  
Taís Nóbrega de Sousa ◽  
Ana Carolina R. Silvino ◽  
Jaques F. de Carvalho ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Amazon Basin ◽  
Ex Vivo ◽  
Hot Spot ◽  
Radical Cure ◽  
Content Type ◽  
Plasmodium Vivax Malaria

ABSTRACT Emerging Plasmodium vivax resistance to chloroquine (CQ) may undermine malaria elimination efforts in South America. CQ-resistant P. vivax has been found in the major port city of Manaus but not in the main malaria hot spots across the Amazon Basin of Brazil, where CQ is routinely coadministered with primaquine (PQ) for radical cure of vivax malaria. Here we randomly assigned 204 uncomplicated vivax malaria patients from Juruá Valley, northwestern Brazil, to receive either sequential (arm 1) or concomitant (arm 2) CQ-PQ treatment. Because PQ may synergize the blood schizontocidal effect of CQ and mask low-level CQ resistance, we monitored CQ-only efficacy in arm 1 subjects, who had PQ administered only at the end of the 28-day follow-up. We found adequate clinical and parasitological responses in all subjects assigned to arm 2. However, 2.2% of arm 1 patients had microscopy-detected parasite recrudescences at day 28. When PCR-detected parasitemias at day 28 were considered, response rates decreased to 92.1% and 98.8% in arms 1 and 2, respectively. Therapeutic CQ levels were documented in 6 of 8 recurrences, consistent with true CQ resistance in vivo. In contrast, ex vivo assays provided no evidence of CQ resistance in 49 local P. vivax isolates analyzed. CQ-PQ coadministration was not found to potentiate the antirelapse efficacy of PQ over 180 days of surveillance; however, we suggest that larger studies are needed to examine whether and how CQ-PQ interactions, e.g., CQ-mediated inhibition of PQ metabolism, modulate radical cure efficacy in different P. vivax-infected populations. (This study has been registered at ClinicalTrials.gov under identifier NCT02691910.)

scholarly journals Plasmodium vivax malaria presenting with severe thrombocytopenia

2002 ◽  
Vol 6 (5) ◽  
Author(s):  
Ravinder Pal Singh Makkar ◽  
Surabhi Mukhopadhyay Amitabh Monga ◽  
Ajay Kr. Gupta
Keyword(s):  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Severe Thrombocytopenia ◽  
Plasmodium Vivax Malaria

scholarly journals Plasmodium vivax Malaria Presenting with Severe Thrombocytopenia

2005 ◽  
Vol 51 (2) ◽  
pp. 120-121 ◽  
Author(s):  
Anju Aggarwal ◽  
Suman Rath ◽  
Shashiraj
Keyword(s):  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Severe Thrombocytopenia ◽  
Plasmodium Vivax Malaria

scholarly journals Resistance to Therapies for Infection by Plasmodium vivax

2009 ◽  
Vol 22 (3) ◽  
pp. 508-534 ◽  
Author(s):  
J. Kevin Baird
Keyword(s):  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Disease Burden ◽  
Ex Vivo ◽  
Severe Disease ◽  
Model Systems ◽  
Complete Neglect ◽  
Continuous Use ◽  
Nearly Continuous

SUMMARY The gravity of the threat posed by vivax malaria to public health has been poorly appreciated. The widely held misperception of Plasmodium vivax as being relatively infrequent, benign, and easily treated explains its nearly complete neglect across the range of biological and clinical research. Recent evidence suggests a far higher and more-severe disease burden imposed by increasingly drug-resistant parasites. The two frontline therapies against vivax malaria, chloroquine and primaquine, may be failing. Despite 60 years of nearly continuous use of these drugs, their respective mechanisms of activity, resistance, and toxicity remain unknown. Although standardized means of assessing therapeutic efficacy against blood and liver stages have not been developed, this review examines the provisional in vivo, ex vivo, and animal model systems for doing so. The rationale, design, and interpretation of clinical trials of therapies for vivax malaria are discussed in the context of the nuance and ambiguity imposed by the hypnozoite. Fielding new drug therapies against real-world vivax malaria may require a reworking of the strategic framework of drug development, namely, the conception, testing, and evaluation of sets of drugs designed for the cure of both blood and liver asexual stages as well as the sexual blood stages within a single therapeutic regimen.

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