Dataset Information

Augmented plasma microparticles during acute Plasmodium vivax infection.

ABSTRACT:

Background

In the last few years, the study of microparticles (MPs)--submicron vesicles released from cells upon activation or apoptosis--has gained growing interest in the field of inflammation and in infectious diseases. Their role in the human malaria parasite Plasmodium vivax remains unexplored. Because acute vivax malaria has been related to pro-inflammatory responses, the main hypothesis investigated in this study was that Plasmodium vivax infection is associated with elevated levels of circulating MPs, which may play a role during acute disease in non-immune patients.

Methods

Plasma MPs were analysed among thirty-seven uncomplicated P. vivax infections from an area of unstable malaria transmission in the Brazilian Amazon. The MP phenotype was analysed by flow cytometry using the classical MP marker, annexin, and fluorochrome-labeled monoclonal antibodies against specific cell surface markers. The frequencies of plasma MPs in P. vivax patients (n=37) were further compared to malaria-unexposed controls (n=15) and ovarian carcinoma patients (n=12), a known MPs-inducing disease non-related to malaria.

Results

The frequencies of plasma circulating MPs were markedly increased in P. vivax patients, as compared to healthy age-matched malaria-unexposed controls. Although platelets, erythrocytes and leukocytes were the main cellular sources of MPs during vivax malaria, platelet derived-MPs (PMPs) increased in a linear fashion with the presence of fever at the time of blood collection (?=0.06, p<0.0001) and length of acute symptoms (?=0.36, p<0.0001). Finally, the results suggest that plasma levels of PMPs diminish as patient experience more episodes of clinical malaria (?=0.07, p<0.003).

Conclusions

Abundant circulating MPs are present during acute P. vivax infection, and platelet derived-MPs may play a role on the acute inflammatory symptoms of malaria vivax.

SUBMITTER: Campos FM

PROVIDER: S-EPMC2998527 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Publications

Augmented plasma microparticles during acute Plasmodium vivax infection.

Campos Fernanda M F FM Franklin Bernardo S BS Teixeira-Carvalho Andréa A Filho Agnaldo L S AL de Paula Sálua C O SC Fontes Cor J CJ Brito Cristiana F CF Carvalho Luzia H LH

Malaria journal 20101116

<h4>Background</h4>In the last few years, the study of microparticles (MPs)--submicron vesicles released from cells upon activation or apoptosis--has gained growing interest in the field of inflammation and in infectious diseases. Their role in the human malaria parasite Plasmodium vivax remains unexplored. Because acute vivax malaria has been related to pro-inflammatory responses, the main hypothesis investigated in this study was that Plasmodium vivax infection is associated with elevated leve ...[more]

PMID: 21080932

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Project description:Plasmodium vivax malaria is a neglected disease, particularly during pregnancy. Severe vivax malaria is associated with inflammatory responses but in pregnancy immune alterations make it uncertain as to what cytokine signatures predominate, and how the type and quantity of blood immune mediators influence delivery outcomes. We measured the plasma concentrations of a set of thirty-one biomarkers, comprising cytokines, chemokines and growth factors, in 987 plasma samples from a cohort of 572 pregnant women from five malaria-endemic tropical countries and related these concentrations to delivery outcomes (birth weight and hemoglobin levels) and malaria infection. Samples were collected at recruitment (first antenatal visit) and at delivery (periphery, cord and placenta). At recruitment, we found that P. vivax-infected pregnant women had higher plasma concentrations of proinflammatory (IL-6, IL-1?, CCL4, CCL2, CXCL10) and TH1-related cytokines (mainly IL-12) than uninfected women. This biomarker signature was essentially lost at delivery and was not associated with birth weight nor hemoglobin levels. Antiinflammatory cytokines (IL-10) were positively associated with infection and poor delivery outcomes. CCL11 was the only biomarker to show a negative association with P. vivax infection and its concentration at recruitment was positively associated with hemoglobin levels at delivery. Birth weight was negatively associated with peripheral IL-4 levels at delivery. Our multi-biomarker multicenter study is the first comprehensive one to characterize the immunological signature of P. vivax infection in pregnancy thus far. In conclusion, data show that while TH1 and pro-inflammatory responses are dominant during P. vivax infection in pregnancy, antiinflammatory cytokines may compensate excessive inflammation avoiding poor delivery outcomes, and skewness toward a TH2 response may trigger worse delivery outcomes. CCL11, a chemokine largely neglected in the field of malaria, emerges as an important marker of exposure or mediator in this condition.

Project description:Malaria is by far the world’s most significant tropical infectious disease and over the last a few decades large-scale malaria epidemics have happened in almost all continents. Plasmodium falciparum and Plasmodium vivax account for over 90% of the total malaria cases worldwide. The estimated number of annual clinical cases of vivax malaria is even higher than that of falciparum malaria, but yet the morbidity associated with this infection and its spectrum of disease is largely neglected. Identification of serum/plasma proteins, which exhibit altered abundance at the onset and during the acute phase of any infection, could be informative to understand the pathobiology of different infectious diseases and host responses against the invading pathogens. To this end, in recent years, quite a few research groups including us have investigated alterations in serum/plasma proteome in severe and non-severe falciparum malaria (and also vivax malaria) to study malaria pathogenesis. In all these studies, serum/plasma proteome of the malaria patients have been analyzed during the febrile stages of the infection, either at the onset of the disease or at the fastigium stage. However, temporal profiling of serum/plasma proteome during acute and remission stages in malaria, which can provide snapshots of the transient and enduring alterations in serum proteome during the febrile, defervescence and convalescent stages has not been reported hitherto. Here, we report, for the first time, serum proteomic alterations in a longitudinal cohort of P. vivax infected patients to elucidate host responses when fever is established (temperature of the body reaches above higher normal level), during the stage when the temperature comes down to normal, and also during the gradual recovery of health after the illness. The three stages discussed in our study have been categorically chosen depending upon the clinical course of uncomplicated vivax malaria. Analysis of the early febrile stage represents host proteome profile immediately after onset of the infection, without any effect of anti-malarial drugs. The second, defervescence stage, reflects any immediate change in blood proteome at early recovery phase, while the convalescent stage indicates a phase after administration of 14 days radical cure treatment with primaquine and a complete recovery, when none of the patients displayed any apparent symptoms of malaria. We have also performed an extensive quantitative proteomics analysis to compare the serum proteome profiles of vivax malaria patients with low and moderately-high parasitemia with healthy community controls. Isobaric tags for relative and absolute quantitation (iTRAQ) and 2-D fluorescence difference gel electrophoresis (2D-DIGE)-based quantitative proteomics approaches were used in the discovery-phase of the study, and some selected differentially abundant serum proteins were validated further by using ELISA. Interestingly, some of the serum proteins like Serum amyloid A, Apolipoprotein A1, C-reactive protein, Titin and Haptoglobin, were found to be sequentially altered with respect to increased parasite counts, while many of the quantified candidates such as Hemopexin, Vitronectin, Clusterin and Apolipoprotein E exhibited nearly equal levels of differential serum abundance in different parasitemic malaria patients. Analysis of a longitudinal cohort of malaria patients indicated reversible alterations in serum levels of some proteins such as Haptoglobin, Apolipoprotein E, Apolipoprotein A1, Carbonic anhydrase 1, and Hemoglobin subunit alpha upon treatment; however, the levels of a few other proteins did not return to the baseline even during the convalescent phase of the infection. Identification of the differentially abundant serum proteins and associated physiological pathways in vivax malaria along with phase-specific protein profiles during the acute and convalescent phases of the infection can effectively enhance our understanding of P. vivax disease biology and host immune responses.

Project description:BackgroundMultiplicity of infection (MOI) refers to the average number of distinct parasite genotypes concurrently infecting a patient. Although several studies have reported on MOI and the frequency of multiclonal infections in Plasmodium falciparum, there is limited data on Plasmodium vivax. Here, MOI and the frequency of multiclonal infections were studied in areas from South America where P. vivax and P. falciparum can be compared.Methodology/principal findingsAs part of a passive surveillance study, 1,328 positive malaria patients were recruited between 2011 and 2013 in low transmission areas from Colombia. Of those, there were only 38 P. vivax and 24 P. falciparum clinically complicated cases scattered throughout the time of the study. Samples from uncomplicated cases were matched in time and location with the complicated cases in order to compare the circulating genotypes for these two categories. A total of 92 P. vivax and 57 P. falciparum uncomplicated cases were randomly subsampled. All samples were genotyped by using neutral microsatellites. Plasmodium vivax showed more multiclonal infections (47.7%) than P. falciparum (14.8%). Population genetics and haplotype network analyses did not detect differences in the circulating genotypes between complicated and uncomplicated cases in each parasite. However, a Fisher exact test yielded a significant association between having multiclonal P. vivax infections and complicated malaria. No association was found for P. falciparum infections.ConclusionThe association between multiclonal infections and disease severity in P. vivax is consistent with previous observations made in rodent malaria. The contrasting pattern between P. vivax and P. falciparum could be explained, at least in part, by the fact that P. vivax infections have lineages that were more distantly related among them than in the case of the P. falciparum multiclonal infections. Future research should address the possible role that acquired immunity and exposure may have on multiclonal infections and their association with disease severity.

Dataset Information

Augmented plasma microparticles during acute Plasmodium vivax infection.

Background

Methods

Results

Conclusions

Publications

Augmented plasma microparticles during acute Plasmodium vivax infection.

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