Direct In Vivo Assessment of Microcirculatory Dysfunction in Severe Falciparum Malaria

Dondorp, Arjen M.; İnce, Can; Charunwatthana, Prakaykaew; Hanson, Josh; Kuijen, Anne-Marije van; Faiz, M. Abul; Rahman, Rezaur; Hasan, Mohammad Rashedul; Yunus, Emran Bin; Ghose, Aniruddha; Ruangveerayut, Ronnatrai; Limmathurotsakul, Direk; Mathura, Keshen R.; White, Nicholas J.; Day, Nicholas P. J.

doi:10.1086/523762

Cited by 216 publications

(212 citation statements)

References 22 publications

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“…21 Such high specificity in the present study might be found with a very sensitive test that is able to detect malaria antigens in the presence of very low parasites that are not detected by microscopy. 24 Such variations within the same test could be explained by the persistence of HRP2 in patients who had been treated 28 days before in case of P. falciparum 12 and the sequestration [25][26][27] Sequestration may reduce the number of circulating parasites to below the microscope threshold detection level. 23 RDT-based diagnosis is vital to make treatment decisions at all health facility levels in general and the peripheral areas in particular, where there is no microscopy.…”

Section: Discussionmentioning

confidence: 99%

Assessing the Performance of CareStart Malaria Pf/Pv Combo Test Against Thick Blood Film in the Diagnosis of Malaria in Northwest Ethiopia

Hailu

Kebede

2014

The American Society of Tropical Medicine and Hygiene

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Abstract. Bivalent rapid diagnostic tests are promising diagnostic tools for Plasmodium falciparum and P. vivax. Their diagnostic performance was evaluated against thick blood smear to assist national malaria control programs. A cross-sectional study was conducted to evaluate the performance of CareStart against thick blood smears among 398 acute febrile patients visiting the Felegeselam Health Center in December of 2011. Thick blood smears were examined under 100 + objectives to diagnose Plasmodium species. Similarly, CareStart Malaria Pf/Pv Combo Test was performed as per the manufacturer's instruction. The ability of CareStart Malaria Pf/Pv Combo Test to diagnose Plasmodium malaria was very good, with 99.8% (95% confidence interval = 97.7-100%) sensitivity and 97.7% (95% confidence interval = 94.6-99.1%) specificity. The sensitivity and specificity of the CareStart Test is comparable with the thick blood smear in diagnosing malaria. Hence, it is preferable to use the CareStart Malaria Pf/Pv Combo Test instead of microscopy in areas where microscopic diagnosis is limited.

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Section: Discussionmentioning

confidence: 99%

Assessing the Performance of CareStart Malaria Pf/Pv Combo Test Against Thick Blood Film in the Diagnosis of Malaria in Northwest Ethiopia

Hailu

Kebede

2014

The American Society of Tropical Medicine and Hygiene

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“…This swelling is partly attributed to venous congestion by the sequestered IRBC mass causing increased cerebral blood volume. 25 Brain herniation is not seen, nor is there evidence of toxigenic or vasogenic edema. 21 This would be in keeping with a lack of detection of albumin or IgG leakage into the CSF of adult patients with CM, in contrast to the significant leakage seen during bacterial meningitis.…”

Section: Clinical Evidence Of Barrier Dysfunction In Severe Malariamentioning

confidence: 98%

“…[50][51][52][53] More recently, obstruction of the microcirculation that is reversed after anti-malarial therapy has also been documented in vivo in acutely infected patients. 25 Sequestration results from the adhesion, or cytoadherence, of IRBC to vascular endothelial cells, and the process is mediated by the variant parasite ligand Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) expressed on the surface of IRBC, and endothelial receptors, of which a number have been implicated. 54,55 Cytoadherence occurs to any significant extent only with P. falciparum that infects human Figure 2.…”

Section: Cytoadherencementioning

confidence: 99%

Dynamic interactions ofPlasmodiumspp. with vascular endothelium

Gillrie

2016

Tissue Barriers

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Plasmodial species are protozoan parasites that infect erythrocytes. As such, they are in close contact with microvascular endothelium for most of the life cycle in the mammalian host. The hostparasite interactions of this stage of the infection are responsible for the clinical manifestations of the disease that range from a mild febrile illness to severe and frequently fatal syndromes such as cerebral malaria and multi-organ failure. Plasmodium falciparum, the causative agent of the most severe form of malaria, is particularly predisposed to modulating endothelial function through either direct adhesion to endothelial receptor molecules, or by releasing potent host and parasite products that can stimulate endothelial activation and/or disrupt barrier function. In this review, we provide a critical analysis of the current clinical and laboratory evidence for endothelial dysfunction during severe P. falciparum malaria. Future investigations using state-of-the-art technologies such as mass cytometry and organs-on-chips to further delineate parasite-endothelial cell interactions are also discussed.

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“…Noninvasive imaging of retinal and rectal vessels in patients with CM clearly demonstrates hypoperfusion and occlusion of the microcirculation, [15][16][17][18][19][20][21] which is reflected by a clear association with a poor clinical outcome. 16,[21][22][23] Murine models of CM have important similarities to CM in humans 2,24 including increased intracranial pressure and a significant decrease in cerebral blood flow, which progressively deteriorates as the clinical condition becomes aggravated. 25 The decrease in cerebral blood flow leads to an altered metabolic profile in the cerebral tissue, which suggests cerebral ischemia.…”

mentioning

confidence: 99%

CNS Hypoxia Is More Pronounced in Murine Cerebral than Noncerebral Malaria and Is Reversed by Erythropoietin

Hempel

Combes

Hunt

et al. 2011

The American Journal of Pathology

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Cerebral malaria (CM) is associated with high mortality and risk of sequelae, and development of adjunct therapies is hampered by limited knowledge of its pathogenesis. To assess the role of cerebral hypoxia, we used two experimental models of CM, Plasmodium berghei ANKA in CBA and C57BL/6 mice, and two models of malaria without neurologic signs, P. berghei K173 in CBA mice and P. berghei ANKA in BALB/c mice. Hypoxia was demonstrated in brain sections using intravenous pimonidazole and staining with hypoxia-inducible factor-1␣-specific antibody. Cytopathic hypoxia was studied using poly (ADP-ribose) polymerase-1 (PARP-1) gene knockout mice. The effect of erythropoietin, an oxygen-sensitive cytokine that mediates protection against CM, on cerebral hypoxia was studied in C57BL/6 mice. Numerous hypoxic foci of neurons and glial cells were observed in mice with CM. Substantially fewer and smaller foci were observed in mice without CM, and hypoxia seemed to be confined to neuronal cell somas. PARP-1-deficient mice were not protected against CM, which argues against a role for cytopathic hypoxia. Erythropoietin therapy reversed the development of CM and substantially reduced the degree of neural hypoxia. These findings demonstrate cerebral hypoxia in malaria, strongly associated with cerebral dysfunction and a possible target for adjunctive therapy.

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Direct In Vivo Assessment of Microcirculatory Dysfunction in Severe Falciparum Malaria

Cited by 216 publications

References 22 publications

Assessing the Performance of CareStart Malaria Pf/Pv Combo Test Against Thick Blood Film in the Diagnosis of Malaria in Northwest Ethiopia

Assessing the Performance of CareStart Malaria Pf/Pv Combo Test Against Thick Blood Film in the Diagnosis of Malaria in Northwest Ethiopia

Dynamic interactions ofPlasmodiumspp. with vascular endothelium

CNS Hypoxia Is More Pronounced in Murine Cerebral than Noncerebral Malaria and Is Reversed by Erythropoietin

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