Estimation of the Total Parasite Biomass in Acute Falciparum Malaria from Plasma PfHRP2

Dondorp, Arjen M.; Desakorn, Varunee; Pongtavornpinyo, Wirichada; Sahassananda, Duangjai; Silamut, Kamolrat; Chotivanich, Kesinee; Newton, Paul N.; Pitisuttithum, Punnee; Smithyman, Anthony M.; White, Nicholas J.; Day, Nicholas P. J.

doi:10.1371/journal.pmed.0020204

Cited by 391 publications

(467 citation statements)

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“…The difficulty in estimating the number of parasites sequestered in tissues has long hampered clinical investigations of malaria, because it is these parasites that are thought to be critical for disease pathogenesis. 39,40 Our data show that Treg depletion results in a major reduction in tissue parasites that may explain why these animals fail to develop ECM.…”

Section: Discussionmentioning

confidence: 80%

A Role for Natural Regulatory T Cells in the Pathogenesis of Experimental Cerebral Malaria

Amante

Stanley

Randall

et al. 2007

The American Journal of Pathology

160

172

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Section: Discussionmentioning

confidence: 80%

A Role for Natural Regulatory T Cells in the Pathogenesis of Experimental Cerebral Malaria

Amante

Stanley

Randall

et al. 2007

The American Journal of Pathology

160

172

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“…Un método más apropiado parece ser la estimación de la biomasa parasitaria, la cual se ha asociado con la gravedad de la enfermedad, al contrario que la parasitemia periférica (40). No se utiliza en la práctica un criterio de hiperparasitemia en las infecciones por P. vivax, posiblemente porque la enfermedad producida por esta especie se ha considerado más benigna.…”

Section: Signos Asociados Con Complicación En El Análisis Bivariadounclassified

Prognostic value of clinical and parasitological signs for severe malaria in patients from Colombia

2012

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Introducción. El pronto reconocimiento de los signos de peligro en los pacientes con malaria puede reducir las complicaciones y muertes. Sin embargo, se conoce poco sobre su valor pronóstico para la malaria complicada, especialmente en las zonas de transmisión baja e inestable de la enfermedad. Objetivo. Estimar el valor pronóstico de gravedad que tienen diversos signos clínicos y parasitológicos en los pacientes con malaria. Materiales y métodos. Se hizo un estudio en una cohorte prospectiva con pacientes de cinco municipios de Colombia, con diagnóstico de malaria por Plasmodium falciparum y P. vivax, en quienes se estudió la asociación de los signos clínicos y los parasitológicos con la malaria complicada. Resultados. Se obtuvo un modelo de predicción con una sensibilidad de 47,4 % y especificidad de 92,8 %, valor pronóstico positivo de 63,2 % y valor pronóstico negativo de 87,1 %, el cual incluye ictericia, orina oscura, hiperpirexia y signos de deshidratación. Conclusiones. Con el fin de causar un impacto en la morbilidad complicada de la malaria, se propone una estrategia de reconocimiento de los signos de peligro por el personal no médico, que se acompañe de otros elementos de la atención, como el suministro de un tratamiento antipalúdico adecuado y oportuno. Se proponen los criterios del diagnóstico de complicación moderada. Palabras clave: malaria, signos y síntomas, Plasmodium falciparum, Plasmodium vivax. Prognostic value of clinical and parasitological signs for severe malaria in patients from ColombiaIntroduction. Early recognition of danger signs in patients with malaria can reduce complications and deaths, but little is known about their prognostic value for severe malaria, especially in areas of low transmission and unstable malaria. Objective. To assess the prognostic value for severity of different clinical and parasitological signs in patients with malaria. Materials and methods. A prospective cohort of patients from five municipalities in Colombia with diagnosis of Plasmodium falciparum or P. vivax malaria in whom the association between clinical and parasitological signs with complicated malaria was studied. Results. A predictive model with 47.4% sensitivity, 92.8% specificity, 63.2% positive predictive value and 87.1% negative predictive value was obtained which includes jaundice, dark urine, hyperpyrexia and signs of dehydration. Conclusions. To impact the morbidity of complicated proposed a strategy is proposed for the early recognition of danger signs by non-medical personnel, which could be complemented by other elements of health care, such as providing adequate and appropriate antimalarial treatment. Diagnostic criteria for moderate complication are also proposed.

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“…According to the TFM, sequestration and/or sequestration-related events is (are) crucial step(s) leading to disease pathogenesis primarily because it is associated with EC activation 8-10, endothelium TF expression, and initiation of the coagulation cascade. Strong support for sequestration in disease pathogenesis comes from IHC and pathology studies performed in African and Asian patients 5 -10, from studies that demonstrated a correlation between sequestration and disease severity using an indirect marker of sequestration 6 , from clinical trials that used artesunate, which targets young and mature forms of the parasite 35 , and from hemoglobinopathies (e.g., hemoglobinopathy C) that protect P. falciparum-infected and (presumably) sequestration-free patients from severe disease 36 ; however, it is clear that sequestration per se does not account for severe disease, as it is also found in uncomplicated cases [1][2][3] .…”

Section: The Tissue Factor Model For Malaria Pathogenesismentioning

confidence: 99%

Does activation of the blood coagulation cascade have a role in malaria pathogenesis?

Francischetti

2008

Trends in Parasitology

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Plasmodium falciparum infection is often associated with a procoagulant state. Recent identification of tissue factor (TF) in the brain endothelium of patients who died from cerebral malaria casts new light in our understanding of the coagulation disorder found in P. falciparum infection. It has also been revealed that parasitized red blood cells (pRBC) support assembly of multimolecular coagulation complexes. In this article, the role of TF expression by the endothelium and amplification of the coagulation cascade by pRBC and/or activated platelets-particularly at sequestration sitesis discussed as crucial events in mounting and sustaining a coagulation-inflammation cycle that contributes to organ dysfunction and coma in P. falciparum malaria. Blood coagulation and malariaMalaria caused by P. falciparum remains a highly endemic disease; it has been estimated that at least one million deaths occur every year. Children are at high risk, and often severe malaria (severe anemia or cerebral malaria [CM]) is the cause of death in this population 1-4. P. falciparum infection is associated with sequestration 5 -8 , endothelial cell (EC) activation 8-10, increase in inflammatory cytokines 3 , 11, and activation of the coagulation cascade 12 -20. Despite several papers devoted to the coagulation disorder in malaria-many of them published during the 1970s and 1980s (reviewed in Ref. 20)-the mechanism that triggers and propagates the coagulation activation in P. falciparum infection has remained elusive. These studies, however, demonstrated that bleeding and/or hemorrhage are typically not present, although laboratory tests indicate a certain degree of in vivo blood coagulation activation 12 -20 . Accordingly, prothrombin time (PT) and partial thromboplastin time (PTT) are close to normal values or prolonged, whereas thrombin-antithrombin complex (TAT) (which indicates in vivo thrombin formation) and D-dimers (which are a marker of in vivo fibrinolysis) are often elevated, and thrombocytopenia is a usual finding 12 -21 . This laboratory profile is compatible with disseminated intravascular coagulation (DIC), which is diagnosed according to a score defined by the International Society of Thrombosis and Haemostasis (ISTH) 22 . The scoring system takes into account i) platelet count, ii) elevated fibrin related markers, iii) prolonged prothrombin time, and iv) fibrinogen level 22 23 . Depending on the score punctuation, levels < 5 are suggestive of non-overt (compensated) DIC while scores > or = 5 are compatible with overt (decompensated) DIC. Bleeding is more common in overt DIC, but it is not needed for the formal diagnosis 22 23. In other words, absence of bleeding in P. falciparum-infected patients does not exclude the presence of DIC in this same population; actually, most of these patients meet the criteria for DIC as defined above 22 . Unfortunately, absence of bleeding is often mistakenly regarded as the reason why DIC is supposedly not present in malaria. Further, some reports do not support the view that coa...

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Estimation of the Total Parasite Biomass in Acute Falciparum Malaria from Plasma PfHRP2

Cited by 391 publications

References 19 publications

A Role for Natural Regulatory T Cells in the Pathogenesis of Experimental Cerebral Malaria

A Role for Natural Regulatory T Cells in the Pathogenesis of Experimental Cerebral Malaria

Prognostic value of clinical and parasitological signs for severe malaria in patients from Colombia

Does activation of the blood coagulation cascade have a role in malaria pathogenesis?

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