41 research outputs found
Clinical Proteomics of the Neglected Human Malarial Parasite Plasmodium vivax
Recent reports highlight the severity and the morbidity of disease caused by the long neglected malaria parasite Plasmodium vivax. Due to inherent difficulties in the laboratory-propagation of P. vivax, the biology of this parasite has not been adequately explored. While the proteome of P. falciparum, the causative agent of cerebral malaria, has been extensively explored from several sources, there is limited information on the proteome of P. vivax. We have, for the first time, examined the proteome of P. vivax isolated directly from patients without adaptation to laboratory conditions. We have identified 153 proteins from clinical P. vivax, majority of which do not show homology to any previously known gene products. We also report 29 new proteins that were found to be expressed in P. vivax for the first time. In addition, several proteins previously implicated as anti-malarial targets, were also found in our analysis. Most importantly, we found several unique proteins expressed by P. vivax.This study is an important step in providing insight into physiology of the parasite under clinical settings
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
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
Comparative evaluation of microscopy, OptiMAL® and 18S rRNA gene based multiplex PCR for detection of Plasmodium falciparum & Plasmodium vivax from field isolates of Bikaner, India
AbstractObjectiveTo evaluate microscopy, OptiMAL® and multiplex PCR for the identification of Plasmodium falciparumm (P. falciparum) and Plasmodium vivax (P. vivax) from the field isolates of Bikaner, Rajasthan (Northwest India).MethodsIn this study, a multiplex PCR (P. falciparum and P. vivax) was further developed with the incorporation of Plasmodium malariae (P. malariae) specific primer and also a positive control. The performance of microscopy, plasmodium lactate dehydrogenase (pLDH) based malaria rapid diagnostic test OptiMAL® and 18S rRNA gene based multiplex PCR for the diagnosis of P. falciparum and P. vivax was compared.ResultsThe three species multiplex PCR (P. falciparum, P. vivax and P. malariae) with an inbuilt positive control was developed and evaluated. In comparison with multiplex PCR, which showed the sensitivity and specificity of 99.36% (95% CI, 98.11%–100.00%) and 100.00% (95% CI, 100.00%–100.00%), the sensitivity and specificity of microscopy was 90.44% (95% CI, 88.84%–95.04%) and 99.22% (95% CI, 97.71%–100.00%), and OptiMAL® was 93.58% (95% CI, 89.75%–97.42%) and 97.69% (95% CI, 95.10%–100.00%). The efficiencies were 99.65%, 95.10% and 95.45% for multiplex PCR, microscopy and OptiMAL®, respectively.ConclusionsOur results raise concerns over the overall sensitivities of microscopy and OptiMAL®, when compared to the multiplex PCR and thus stress the need for new molecular interventions in the accurate detection of the malarial parasites. This further highlights the fact that further developments are needed to improve the performance of rapid diagnostic tests at field level
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 23.3 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