Quantification of Plasmodium falciparum Histidine-Rich Protein-2 in Cerebrospinal Spinal Fluid from Cerebral Malaria Patients

Mikita, Kei; Thakur, Kiran T.; Anstey, Nicholas M.; Piera, Kim A.; Pardo, Carlos A.; Weinberg, J. Brice; Mukemba, Jackson; Florence, Salvatore M.; Mwaikambo, Esther D.; Granger, Donald L.; Sullivan, David J.

doi:10.4269/ajtmh.14-0210

Cited by 10 publications

(8 citation statements)

References 26 publications

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“…Estimation of Plasmodium falciparum histidine rich protein 2 (PfHRP2) in the plasma samples has also been shown to be an accurate diagnostic tool to ascertain the parasite biomass in severe malaria patients, and allowed the distinction between severe and uncomplicated malaria (Hendriksen et al, 2012 ; Imwong et al, 2015 ). Clinical studies have also shown that PfHRP2 can be present in the CSF of patients with CM (Mikita et al, 2014 ). More recently, the use of advanced affinity-proteomic tools employing a high-throughput platform of specific antibodies for candidate screening has allowed a wider analysis of potential diagnosis biomarkers for the neuropathology.…”

Section: Biomarkersmentioning

confidence: 99%

Pathogenesis of cerebral malaria: new diagnostic tools, biomarkers, and therapeutic approaches

Sahu

Satpathi

Behera

et al. 2015

Front. Cell. Infect. Microbiol.

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Cerebral malaria is a severe neuropathological complication of Plasmodium falciparum infection. It results in high mortality and post-recovery neuro-cognitive disorders in children, even after appropriate treatment with effective anti-parasitic drugs. While the complete landscape of the pathogenesis of cerebral malaria still remains to be elucidated, numerous innovative approaches have been developed in recent years in order to improve the early detection of this neurological syndrome and, subsequently, the clinical care of affected patients. In this review, we briefly summarize the current understanding of cerebral malaria pathogenesis, compile the array of new biomarkers and tools available for diagnosis and research, and describe the emerging therapeutic approaches to tackle this pathology effectively.

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Section: Biomarkersmentioning

confidence: 99%

Pathogenesis of cerebral malaria: new diagnostic tools, biomarkers, and therapeutic approaches

Sahu

Satpathi

Behera

et al. 2015

Front. Cell. Infect. Microbiol.

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“…IHC using monoclonal antibody 3A4 [ 14 , 15 ] to P. falciparum histidine-rich protein 2 (HRP2) was carried out on 5 mm thick, formalin-fixed, paraffin-embedded sections using automated IHC stainer (Bond Leica, Leica Microsystems, Bannockburn, IL, USA) at the Johns Hopkins Immunopathology Research Laboratory as previously described [ 16 ]. Slides were deparaffinized and hydrated, and heat-induced antigen retrieval step was performed using citrate buffer (pH 6.0).…”

Section: Methodsmentioning

confidence: 99%

Diagnosis of placental malaria in poorly fixed and processed placental tissue

Griffin

Muehlenbachs

Rogerson

et al. 2016

Malar J

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BackgroundPlacental histopathology has been considered the gold standard for diagnosis of malaria during pregnancy. However, in under-resourced areas placental tissue is often improperly fixed and processed; the resulting formalin pigment is difficult to distinguish from malaria pigment. This study examines two alternative diagnostic methods: polymerase chain reaction (PCR) and a novel immunohistochemistry (IHC)-based method using an antibody against histidine-rich protein 2 (HRP2).MethodsPlacental histopathology from 151 pregnant women in Kinshasa was assessed by two blinded microscopists and compared with peripheral blood PCR and IHC for HRP2. The Cohen’s kappa coefficients were calculated to assess the test agreement. The sensitivity and specificity of individual tests were calculated using PCR or IHC as the reference standard as well as latent class analysis (LCA).ResultsPCR and IHC correlated fairly well. The correlation between the two blinded microscopists was poor, as there was widespread formalin pigment. Using LCA, all of the tests had high specificities. The most sensitive test was IHC (67.7 %), with PCR as second-best (56.1 %).ConclusionsPCR and/or IHC are suitable diagnostics when the presence of formalin pigment substantially compromises placental histopathology.

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“…This study therefore focuses on the measurement of PfHRP-2 in the CSF compartment. PfHRP-2 has previously been quantified in the CSF of patients with CM, though samples in this previous study were obtained without information on malaria retinopathy status [ 27 ]. Here, the authors report quantitative CSF PfHRP-2 levels in a cohort of retinopathy-positive CM children to determine whether there is a relationship between CSF PfHRP-2 and clinical, laboratory and radiographic features of interest.…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal fluid Plasmodium falciparum histidine-rich protein-2 in pediatric cerebral malaria

Thakur

Vareta

Carson

et al. 2018

Malar J

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BackgroundCerebral malaria (CM) causes a rapidly developing coma, and remains a major contributor to morbidity and mortality in malaria-endemic regions. This study sought to determine the relationship between cerebrospinal fluid (CSF) Plasmodium falciparum histidine rich protein-2 (PfHRP-2) and clinical, laboratory and radiographic features in a cohort of children with retinopathy-positive CM.MethodsPatients included in the study were admitted (2009–2013) to the Pediatric Research Ward (Queen Elizabeth Central Hospital, Blantyre, Malawi) meeting World Health Organization criteria for CM with findings of malarial retinopathy. Enzyme-linked immunosorbent assay was used to determine plasma and CSF PfHRP-2 levels. Wilcoxon rank-sum tests and multivariable logistic regression analysis assessed the association of clinical and radiographic characteristics with the primary outcome of death during hospitalization.ResultsIn this cohort of 94 patients, median age was 44 (interquartile range 29–62) months, 53 (56.4%) patients were male, 6 (7%) were HIV-infected, and 10 (11%) died during hospitalization. Elevated concentrations of plasma lactate (p = 0.005) and CSF PfHRP-2 (p = 0.04) were significantly associated with death. On multivariable analysis, higher PfHRP-2 in the CSF was associated with death (odds ratio 9.00, 95% confidence interval 1.44–56.42) while plasma PfHRP-2 was not (odds ratio 2.05, 95% confidence interval 0.45–9.35).ConclusionsElevation of CSF, but not plasma PfHRP-2, is associated with death in this paediatric CM cohort. PfHRP-2 egress into the CSF may represent alteration of blood brain barrier permeability related to the sequestration of parasitized erythrocytes in the cerebral microvasculature.Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2272-y) contains supplementary material, which is available to authorized users.

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Quantification of Plasmodium falciparum Histidine-Rich Protein-2 in Cerebrospinal Spinal Fluid from Cerebral Malaria Patients

Cited by 10 publications

References 26 publications

Pathogenesis of cerebral malaria: new diagnostic tools, biomarkers, and therapeutic approaches

Pathogenesis of cerebral malaria: new diagnostic tools, biomarkers, and therapeutic approaches

Diagnosis of placental malaria in poorly fixed and processed placental tissue

Cerebrospinal fluid Plasmodium falciparum histidine-rich protein-2 in pediatric cerebral malaria

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