The pathophysiology of falciparum malaria

Clark, Ian A.; Cowden, W. B.

doi:10.1016/s0163-7258(03)00060-3

Cited by 184 publications

(175 citation statements)

References 383 publications

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“…This finding is of clinical significance both in assessing the risk of bleeding in malaria patients and in monitoring disease progression and/ or recovery because improvement in the platelet count would reflect arrest and even reversal of the complex processes that lead to thrombocytopenia in malaria in the first place. Improvement in platelet count has been directly correlated with clinical recovery in malaria [1,2]. In this study too, we followed up the laboratory parameters, including the platelet count regularly in all these cases during their hospital stay (data not shared here) and noticed improvement in the platelet counts as the patients responded to the antimalarial treatment.…”

Section: Discussionmentioning

confidence: 83%

“…Some other workers have noted that although mild to moderate thrombocytopenia is a common finding in malaria, hemorrhagic manifestations and clinical evidence of disseminated intravascular coagulation (DIC) are rare (*5 and 5-10% respectively) [2]. In contrast to these reports, hemorrhagic manifestations were observed in 25% cases of P. falciparum and 30% cases of P. vivax in this study and there was a clear-cut correlation between thrombocytopenia and incidence hemorrhage in both P. vivax and P. falciparum (Table 1) [8].…”

Section: Discussionmentioning

confidence: 99%

“…A direct interaction between the parasites and the endothelium of the microcirculation causes endothelial cell injury and sets up a series of reactions characterized by release of a large variety of cytokines and inflammatory mediators by the endothelium, the leucocytes and the other cells in the body. These in turn activate the coagulation pathway leading to widespread thrombin deposition in small arteries and arterioles (disseminated intravascular coagulation) and fibrinolysis [2]. This explains the abnormalities of a number of coagulation parameters, including the markers of thrombosis and fibrinolysis that have been reported in malaria [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

“…These in turn activate the coagulation pathway leading to widespread thrombin deposition in small arteries and arterioles (disseminated intravascular coagulation) and fibrinolysis [2]. This explains the abnormalities of a number of coagulation parameters, including the markers of thrombosis and fibrinolysis that have been reported in malaria [1][2][3]. However, attempts to use these laboratory parameters as indicators of the severity of the underlying coagulopathy and for monitoring disease progression have met with only a partial success [4].…”

Section: Introductionmentioning

confidence: 99%

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Persistently Elevated Laboratory Markers of Thrombosis and Fibrinolysis After Clinical Recovery in Malaria Points to Residual and Smouldering Cellular Damage

Dasgupta¹,

Rai²,

Gupta³

2011

Indian J Hematol Blood Transfus

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Screening coagulation tests and assays for thrombosis and fibrinolysis were performed in 80 cases of malaria at presentation and during the course of the disease. Close correlation between the degree of thrombocytopenia (observed in [97% cases) and the presence hemorrhagic manifestations at presentation, and improvement in the platelet count in parallel with clinical recovery emphasised the role of platelets in the pathogenesis of coagulopathy in malaria. A potential selection bias resulting from inclusion of only patients admitted at a tertiary care hospital could explain the higher incidence (27.5%) of clinical bleeding observed in this study compared to that reported in the literature. Although a significant correlation between overt bleeding and abnormal PT/INR and APTT (observed in 20-37% cases) could not be demonstrated, a good correlation existed between normal screening coagulation tests and the absence of bleeding complications. Elevated D-Dimer and FDP levels in almost all cases (90%) of both types of malaria confirmed the high prevalence of disseminated intravascular coagulation and fibrinolysis. A correlation between rising D-Dimer levels and the incidence of bleeding was observed. Follow up studies in six cases with complications showed normalization of platelet counts and of screening coagulation assays with clinical recovery. D-Dimer and FDP levels however, remained elevated in most of these cases indicating the continuation of a smouldering coagulopathy even after full clinical recovery possibly due to the persistence of residual damage to the cells caused by the parasitic infection. Knowledge of this fact is important for avoiding unnecessary investigations and longer hospital stay in patients admitted with malaria.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Persistently Elevated Laboratory Markers of Thrombosis and Fibrinolysis After Clinical Recovery in Malaria Points to Residual and Smouldering Cellular Damage

Dasgupta¹,

Rai²,

Gupta³

2011

Indian J Hematol Blood Transfus

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“…Finally, NO seems to play an important role in the pathogenesis of P falciparum malaria both as antiplasmodial agent and regulator of the immune response to the parasite. This suggested the hypothesis that derivatives of NO could be effective antimalarial agents [5]. Indeed, it was found that some NO-donors display in vitro toxic action against P. falciparum [6][7][8].…”

Section: Introductionmentioning

confidence: 96%

Amodiaquine analogues containing NO-donor substructures: Synthesis and their preliminary evaluation as potential tools in the treatment of cerebral malaria

Bertinaria¹,

Guglielmo²,

Rolando³

et al. 2011

European Journal of Medicinal Chemistry

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The synthesis and physico-chemical properties of novel compounds obtained by conjugation of amodiaquine with moieties containing either furoxan or nitrooxy NO-donor substructures are described. The synthesised compounds were tested in vitro against both the chloroquine sensitive , D10 and the chloroquine resistant, W-2 strains of Plasmodium falciparum (P. falciparum). Most of the compounds showed an antiplasmodial activity comparable to that of the parent drug. By comparing the activities of simple related structures devoid of the ability to release NO, it appears that the contribution of NO to the antiplasmodial action in vitro is marginal. All the compounds were able to relax rat aorta strips with a NO-dependent mechanism, thus showing their capacity to release NO in the vessels. A preliminary in vivo study using Plasmodium berghei ANKA-infected mice showed a trend for prolonged survival of mice with cerebral malaria treated with compound † Authors contributed equally to this work * Corresponding author. Tel.: +39 011 6707670; fax: +39 011 6707286. E-mail address: alberto.gasco@unito.it (A.Gasco).3 40, which is potent and fast amodiaquine-derived NO donor, when compared with amodiaquine alone or with compound 31, a milder NO-donor. The two compounds showed in vivo antiplasmodial activity similar to that of amodiaquine.

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Experimental Asexual Blood Stage Malaria Immunity

2011

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Immunity to asexual blood stages of malaria is complex, involving both humoral and cell-mediated immune mechanisms. The availability of murine models of malaria has greatly facilitated the analysis of immune mechanisms involved in resistance to the asexual blood stages. This unit details the materials and methods required for inducing protective immunity toward experimental blood stage malaria parasites by vaccination, repeated infection, and drug cure, as well as adoptive transfer of antigen-specific T cells.

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The pathophysiology of falciparum malaria

Cited by 184 publications

References 383 publications

Persistently Elevated Laboratory Markers of Thrombosis and Fibrinolysis After Clinical Recovery in Malaria Points to Residual and Smouldering Cellular Damage

Persistently Elevated Laboratory Markers of Thrombosis and Fibrinolysis After Clinical Recovery in Malaria Points to Residual and Smouldering Cellular Damage

Amodiaquine analogues containing NO-donor substructures: Synthesis and their preliminary evaluation as potential tools in the treatment of cerebral malaria

Experimental Asexual Blood Stage Malaria Immunity

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