37 research outputs found
Plasmodium vivax Malaria
We report 11 cases of severe Plasmodium vivax malaria in Bikaner (western India). Patients exhibited cerebral malaria, renal failure, circulatory collapse, severe anemia, hemoglobinurea, abnormal bleeding, acute respiratory distress syndrome, and jaundice. Peripheral blood microscopy, parasite antigen–based assays, and parasite 18s rRNA gene–based polymerase chain reaction showed the presence of P. vivax and absence of P. falciparum
Naturally Acquired Binding-Inhibitory Antibodies to Plasmodium vivax Duffy Binding Protein in Pregnant Women Are Associated with Higher Birth Weight in a Multicenter Study
A vaccine to eliminate malaria would need a multi-stage and
multi-species composition to achieve robust protection, but the
lack of knowledge about antigen targets and mechanisms of
protection precludes the development of fully efficacious
malaria vaccines, especially for Plasmodium vivax (Pv). Pregnant
women constitute a risk population who would greatly benefit
from a vaccine preventing the adverse events of Plasmodium
infection during gestation. We hypothesized that functional
immune responses against putative targets of naturally acquired
immunity to malaria and vaccine candidates will be associated
with protection against malaria infection and/or poor outcomes
during pregnancy. We measured (i) IgG responses to a large panel
of Pv and Plasmodium falciparum (Pf) antigens, (ii) the capacity
of anti-Pv ligand Duffy binding protein (PvDBP) antibodies to
inhibit binding to Duffy antigen, and (iii) cellular immune
responses to two Pv antigens, in a subset of 1,056 pregnant
women from Brazil, Colombia, Guatemala, India, and Papua New
Guinea (PNG). There were significant intraspecies and
interspecies correlations for most antibody responses (e.g.,
PfMSP119 versus PfAMA1, Spearman's rho = 0.81). Women from PNG
and Colombia had the highest levels of IgG overall.
Submicroscopic infections seemed sufficient to boost antibody
responses in Guatemala but not antigen-specific cellular
responses in PNG. Brazil had the highest percentage of Duffy
binding inhibition (p-values versus Colombia: 0.040; Guatemala:
0.047; India: 0.003, and PNG: 0.153) despite having low
anti-PvDBP IgG levels. Almost all antibodies had a positive
association with present infection, and coinfection with the
other species increased this association. Anti-PvDBP,
anti-PfMSP1, and anti-PfAMA1 IgG levels at recruitment were
positively associated with infection at delivery (p-values:
0.010, 0.003, and 0.023, respectively), suggesting that they are
markers of malaria exposure. Peripheral blood mononuclear cells
from Pv-infected women presented fewer CD8+IFN-gamma+ T cells
and secreted more G-CSF and IL-4 independently of the stimulus
used in vitro. Functional anti-PvDBP levels at recruitment had a
positive association with birth weight (difference per doubling
antibody levels: 45 g, p-value: 0.046). Thus, naturally acquired
binding-inhibitory antibodies to PvDBP might confer protection
against poor outcomes of Pv malaria in pregnancy
Blood cytokine, chemokine and growth factor profiling in a cohort of pregnant women from tropical countries
The immune status of women changes during and after pregnancy, differs between blood compartments at delivery and is affected by environmental factors particularly in tropical areas endemic for multiple infections. We quantified the plasma concentration of a set of thirty-one TH1, TH2, TH17 and regulatory cytokines, pro-inflammatory and anti-inflammatory cytokines and chemokines, and growth factors (altogether biomarkers), in a cohort of 540 pregnant women from five malaria-endemic tropical countries. Samples were collected at recruitment (first antenatal visit), delivery (periphery, cord and placenta) and postpartum, allowing a longitudinal analysis. We found the lowest concentration of biomarkers at recruitment and the highest at postpartum, with few exceptions. Among them, IL-6, HGF and TGF-β had the highest levels at delivery, and even higher concentrations in the placenta compared to peripheral blood. Placental concentrations were generally higher than peripheral, except for eotaxin that was lower. We also compared plasma biomarker concentrations between the tropical cohort and a control group from Spain at delivery, presenting overall higher biomarker levels the tropical cohort, particularly pro-inflammatory cytokines and growth factors. Only IL-6 presented lower levels in the tropical group. Moreover, a principal component analysis of biomarker concentrations at delivery showed that women from Spain grouped more homogenously, and that IL-6 and IL-8 clustered together in the tropical cohort but not in the Spanish one. Plasma cytokine concentrations correlated with Plasmodium antibody levels at postpartum but not during pregnancy. This basal profiling of immune mediators over gestation and in different compartments at delivery is important to subsequently understand response to infections and clinical outcomes in mothers and infants in tropical areas
Microsatellite Genotyping of Plasmodium vivax Isolates from Pregnant Women in Four Malaria Endemic Countries
Plasmodium vivax is the most widely distributed human parasite
and the main cause of human malaria outside the African
continent. However, the knowledge about the genetic variability
of P. vivax is limited when compared to the information
available for P. falciparum. We present the results of a study
aimed at characterizing the genetic structure of P. vivax
populations obtained from pregnant women from different malaria
endemic settings. Between June 2008 and October 2011 nearly 2000
pregnant women were recruited during routine antenatal care at
each site and followed up until delivery. A capillary blood
sample from the study participants was collected for genotyping
at different time points. Seven P. vivax microsatellite markers
were used for genotypic characterization on a total of 229 P.
vivax isolates obtained from Brazil, Colombia, India and Papua
New Guinea. In each population, the number of alleles per locus,
the expected heterozygosity and the levels of multilocus linkage
disequilibrium were assessed. The extent of genetic
differentiation among populations was also estimated. Six
microsatellite loci on 137 P. falciparum isolates from three
countries were screened for comparison. The mean value of
expected heterozygosity per country ranged from 0.839 to 0.874
for P. vivax and from 0.578 to 0.758 for P. falciparum. P. vivax
populations were more diverse than those of P. falciparum. In
some of the studied countries, the diversity of P. vivax
population was very high compared to the respective level of
endemicity. The level of inter-population differentiation was
moderate to high in all P. vivax and P. falciparum populations
studied
Comparison of the safety and efficacy of fixed-dose combination of arterolane maleate and piperaquine phosphate with chloroquine in acute, uncomplicated Plasmodium vivax malaria: a phase III, multicentric, open-label study
Case Report - Acute intermittent porphyria presenting with neurological emergency: Review of six cases
Acute intermittent porphyria presenting with short duration of
gastrointestinal symptoms followed by rapidly progressive fulminant
neurological syndrome during first attack is relatively uncommon. It is
a neurological emergency and mimics many other psychiatric and medical
disorders and can be fatal if it remains undiagnosed and untreated.
Further, specific treatment in the form of Heme arginate is not
universally available and very costly, so high clinical suspicion and
early diagnosis and management of acute attack and prevention of
further attacks are very important. We report a series of six cases who
presented with convulsion and/or polyneuropathy early in the course of
disease to highlight this fact
Acute attack of AIP (acute intermittent porphyria) with severe vivax malaria associated with convulsions: a case report
A cross strain Plasmodium falciparum microarray optimized for the transcriptome analysis of Plasmodium falciparum patient derived isolates
Malarial parasite P. falciparum, an apicomplexan protozoan has a 23.3Â MB nuclear genome and encodes ~5600 transcripts. The genetic diversity of the parasite within and across geographical zones is a challenge to gene expression studies which are essential for understanding of disease process, outcome and developing markers for diagnostics and prognostics. Here, we describe the strategy involved in designing a custom P. falciparum 15K array using the Agilent platform and Genotypic's Right Design methodology to study the transcriptome of Indian field isolates for which genome sequence information is limited. The array contains probes representing genome sequences of two distinct geographical isolates (i.e. 3D7 and HB3) and sub-telomeric var gene sequences of a third isolate (IT4) known to adhere in culture condition. Probes in the array have been selected based on their efficiency to detect transcripts through a 244K array experimentation. Array performance for the 15K array, was evaluated and validated using RNA materials from P. falciparum clinical isolates. A large percentage (91%) of the represented transcripts was detected from Indian P. falciparum patient isolates. Replicated probes and multiple probes representing the same gene showed perfect correlation between them suggesting good probe performance. Additional transcripts could be detected due to inclusion of unique probes representing HB3 strain transcripts. Variant surface antigen (VSA) transcripts were detected by optimized probes representing the VSA genes of three geographically distinct strains. The 15K cross strain P. falciparum array has shown good efficiency in detecting transcripts from P. falciparum parasite samples isolated from patients. The low parasite loads and presence of host RNA makes arrays a preferred platform for gene expression studies over RNA-Seq
Dataset of natural antisense transcripts in P. vivax clinical isolates derived using custom designed strand-specific microarray
Natural antisense transcripts (NATs) have been detected in many organisms and shown to regulate gene expression. Similarly, NATs have also been observed in malaria parasites with most studies focused on Plasmodium falciparum. There were no reports on the presence of NATs in Plasmodium vivax, which has also been shown to cause severe malaria like P. falciparum, until a recent study published by us. To identify in vivo prevalence of antisense transcripts in P. vivax clinical isolates, we performed whole genome expression profiling using a custom designed strand-specific microarray that contains probes for both sense and antisense strands. Here we describe the experimental methods and analysis of the microarray data available in Gene Expression Omnibus (GEO) under GSE45165. Our data provides a resource for exploring the presence of antisense transcripts in P. vivax isolated from patients showing varying clinical symptoms. Related information about the description and interpretation of the data can be found in a recent publication by Boopathi and colleagues in Infection, Genetics and Evolution 2013