Intravenous Artesunate Reduces Parasite Clearance Time, Duration of Intensive Care, and Hospital Treatment in Patients With Severe Malaria in Europe: The TropNet Severe Malaria Study: Figure 1.

Kurth, Florian; Develoux, M.; Méchain, Matthieu; Clerinx, Jan; Antinori, Spinello; Gjørup, Ida; Gascón, Joaquim; Mørch, Kristine; Nicastri, Emanuele; Ramharter, Michael; Bartoloni, Alessandro; Visser, Leo G.; Rolling, Thierry; Zanger, Philipp; Calleri, Guido; Salas-Coronas, Joaquín; Nielsen, Henrik; Just‐Nübling, G.; Neumayr, Andreas; Hachfeld, Anna; Schmid, Matthias; Antonini, Pietro; Pongratz, Peter; Kern, Peter; Cunha, José Saraiva da; Soriano‐Arandes, Antoni; Schunk, Mirjam; Suttorp, Norbert; Hatz, Christoph; Zöller, Thomas

doi:10.1093/cid/civ575

Cited by 39 publications

(26 citation statements)

References 9 publications

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“…We suggest that drug-induced pitting should be evaluated early in the development of new generations of antimalarial molecules such as spiroindolones [11], which have an effect on ring circulating forms. This would help better grasp their mode of action in vivo, which helps predict the risk of posttreatment hemolysis observed in severe [4,[12][13][14] and more recently in uncomplicated malaria [9,15]. In the context of artemisinin resistance in Southeast Asia characterized by slow parasite clearance, a specific study on the role of pitting may explain how parasites initially escape clearance mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Plasmodium falciparum Clearance Is Pitting-Dependent With Artemisinin-Based Drugs but Pitting-Independent With Atovaquone-Proguanil or Mefloquine

Wojnarski

Mouri

Chambrion

et al. 2019

The Journal of Infectious Diseases

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Pitting, the removal of dead parasites from their host erythrocyte, has been studied in patients with severe malaria treated parenterally with quinine or artesunate, and was recently shown to contribute to delayed hemolysis, a frequent adverse event of artesunate. We quantified pitting in 81 travelers treated with oral antimalarial therapy. Pitting rate was high (55.8%) with artemisinin-based combinations, but <10% with the nonartemisinin drugs quinine, mefloquine, and atovaquone-proguanil. This may, in part, explain the slower parasite clearance in patients treated with antimalarial drugs lacking an artemisinin component, as well as the absence of posttreatment hemolysis with these drugs.

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Section: Discussionmentioning

confidence: 99%

Plasmodium falciparum Clearance Is Pitting-Dependent With Artemisinin-Based Drugs but Pitting-Independent With Atovaquone-Proguanil or Mefloquine

Wojnarski

Mouri

Chambrion

et al. 2019

The Journal of Infectious Diseases

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“…Their mortality rates were higher than in our study, with death occurring during the first week of hospitalization in three out of four patients. In these two studies, the proportion of patients needing the use of vasopressors, mechanical ventilation or renal replacement therapy is shown in table E1, as well as a review of other studies of severe imported malaria [8,23,24]. The risk factors associated with mortality in the SIMA cohort study were an older age, a low Glasgow Coma Scale score and a high parasitemia.…”

Section: Discussionmentioning

confidence: 99%

“…The TropNet severe malaria study showed that a treatment with artesunate reduced the parasite clearance time and was associated with shorter ICU and hospital lengths-of-stay [8]. The initiation of an anti-malarial treatment is an emergency and previous studies demonstrated that a better prognostic was associated with a shorter time between the first symptoms and the initiation of treatment administration [27,28].…”

Section: Discussionmentioning

confidence: 99%

“…Available in compassionate use in France since May 2011, artesunate became the first-line treatment for severe malaria. This drug is associated with a reduced mortality in endemic areas [6,7], was shown to improve survival versus quinine in South-East Asia and Africa, to reduce parasite clearance time, and to shorten the ICU and hospital lengths of stay in non-endemic countries [8]. Its effectiveness and tolerance made it a good choice to replace intravenous quinine in European countries.…”

Section: Introductionmentioning

confidence: 99%

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Changes in the clinical presentation and outcomes of patients treated for severe malaria in a referral French university intensive care unit from 2004 to 2017

Lebut

Mourvillier

Argy

et al. 2020

Ann. Intensive Care

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Background In France, the incidence of severe imported malaria cases increased since early 2000. Artesunate was available (temporarily use authorization) since mid-2011 in France and commonly used for severe malaria since early 2013. Thus, the study objectives were to describe the patients with severe imported malaria admitted in intensive care unit (ICU) and assess the changes in clinical presentation and outcomes before and after this date. Methods Retrospective observational single-center study in the infectious diseases ICU of a referral university hospital, conducted on patients admitted for severe imported malaria from 2004 to 2017. Demographic variables, severity scores, WHO’s severity criteria on admission, treatment, and ICU and hospital lengths of stay were collected. Patients’ characteristics and outcomes were compared between both periods. A poor outcome was defined as the composite endpoint of death, or requirement for vasopressors, invasive mechanical ventilation and/or renal replacement therapy. Results 189 patients were included, 98 in 2004–2012 and 91 in 2013–2017, most often from West and Central African countries (96%). The number of WHO criteria for severe malaria was comparable in both groups, but SAPS II, SOFA and ICU length of stay were significantly higher in 2004–2012, while patients of African origin living in France were less frequent (p < 0.01). The outcome was poor for 41/98 cases in 2004–2012 and 12/91 cases in 2013–2017 (p < 0.01). The risk factors of poor outcome on the multivariate logistic regression were a neurological failure (adjusted odds ratio (adjOR = 3.23; 95% CI (1.03–10.08), p = 0.004), cardio-circulatory failure (adjOR = 9.92; 95% CI (2.34–42), p = <0.01) and creatinine blood levels > 265 µmol/L (adjOR = 10.76; 95% CI (3.17–36.53), p < 0.01). In the multivariate analysis, IV artesunate was not associated with a better outcome. Patients of African origin did not seem to have a better outcome than Caucasian patients or those from other origins (adjOR = 0.59; 95% CI (0.21–1.65), p = 0.31). Conclusion Patients with imported malaria admitted in ICU in 2013–2017 were less severely ill than those in 2004–2012. These trends could be partially explained by the increasing proportion of African patients visiting friends or relatives or living in endemic areas.

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“…Reply to Jaureguiberry et al TO THE EDITOR-We thank Dr Jauréguiberry and his colleagues for their interest in our study [1] and appreciate their remarks [2].…”

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confidence: 95%

Reply to Jaureguiberry et al

Kurth

Zöller

2015

Clin Infect Dis.

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Intravenous Artesunate Reduces Parasite Clearance Time, Duration of Intensive Care, and Hospital Treatment in Patients With Severe Malaria in Europe: The TropNet Severe Malaria Study: Figure 1.

Cited by 39 publications

References 9 publications

Plasmodium falciparum Clearance Is Pitting-Dependent With Artemisinin-Based Drugs but Pitting-Independent With Atovaquone-Proguanil or Mefloquine

Plasmodium falciparum Clearance Is Pitting-Dependent With Artemisinin-Based Drugs but Pitting-Independent With Atovaquone-Proguanil or Mefloquine

Changes in the clinical presentation and outcomes of patients treated for severe malaria in a referral French university intensive care unit from 2004 to 2017

Reply to Jaureguiberry et al

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