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ABSTRACT: Cerebral malaria (CM) is still responsible for unacceptable death rate, while new antimalarial drugs were recently developed. CM pathophysiology shares essential biological features with cerebral ischemia. Because erythropoietin (Epo) was demonstrated to reduce mortality rate during experimental cerebral ischemia (1), in the early 2000, we wondered whether Epo could help to reduce the burden of CM. There is now evidence that Epo high doses could prevent early mortality during cerebral malaria. This evidence was obtained first using mice model of cerebral malaria, and later confirmed by prospective clinical trial in endemic area. High doses of Epo are needed to cross the blood-brain barrier (see Note 1) and to favor the cytoprotective versus hematopoietic effect of this pleiotropic cytokine (see Note 2).
Methods in molecular biology (Clifton, N.J.) 01/2013; 982:315-24.
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ABSTRACT: Since the outcomes of patients with candidemia is poor and Candida spp. with increased resistance to antifungal therapy may be associated with these results, the emergence of these blood infections caused by non-C. albicans Candida spp. was explored prospectively over a two-year period (2009-2010). Candidemia was defined as the recovery of Candida spp. in culture from a patient's blood sample. The in vitro susceptibility of each isolate to amphotericin B, caspofungin, fluconazole and voriconazole was determined. In addition, characteristics of patients and outcomes were investigated in real-time. The Candida distribution was compared to that observed in a similar study 10 years earlier in the same hospital. A total of 182 patients with candidemia were included in the study. While C. albicans was the most frequently isolated species (n = 102), non-C. albicans Candida spp. included; C. glabrata (n = 32), C. parapsilosis (n = 21), C. tropicalis (n = 13), C. krusei (n = 8), C. kefyr (n = 3), C. lusitaniae (n = 2), C. lipolytica (n = 2), C. famata (n = 1), C. guilliermondii (n = 1), C. inconspicua (n = 1), C. dubliniensis (n = 1), C. sake (n = 1) and C. nivariensis (n = 1). In seven patients, C. albicans was associated with another Candida spp. Surprisingly, this prospective study demonstrated that regardless of the department (intensive care unit or hematological department), Candida spp. distribution was no different from that found in the 1998-2001 survey, except for C. krusei. A reduction in the proportion of C. krusei isolates was observed from 2000-2010 (P = 0.028) as a result of its decreased recovery in the hematological department.
Medical mycology: official publication of the International Society for Human and Animal Mycology 06/2012; · 2.13 Impact Factor
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Marie-Christine Nicolle,
Thomas Bénet,
Anne Thiebaut, Anne-Lise Bienvenu,
Nicolas Voirin,
Antoine Duclos,
Mohamad Sobh,
Giovanna Cannas,
Xavier Thomas,
Frank-Emmanuel Nicolini,
Frédérique De Monbrison,
Marie-Antoinette Piens,
Stéphane Picot,
Mauricette Michallet,
Philippe Vanhems
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ABSTRACT: The study objectives were: 1) to report on invasive aspergillosis patients in a hematology department; and 2) to estimate its incidence according to the hematologic diagnosis.
A prospective survey of invasive aspergillosis cases was undertaken between January 2004 and December 2009 in the hematology department of a university hospital. Meetings with clinicians, mycologists and infection control practitioners were organized monthly to confirm suspected aspergillosis cases. Demographic characteristics, clinical and complementary examination results were recorded prospectively. Information on hospitalization was extracted from administrative databases. Invasive aspergillosis diagnosis followed the European Organization for Research and Treatment of Cancer criteria, and proven and probable IA cases were retained. A descriptive analysis was conducted with temporal trends of invasive aspergillosis incidence assessed by adjusted Poisson regression.
Overall, 4,073 hospitalized patients (78,360 patient-days) were included in the study. In total, 127 (3.1%) patients presented invasive aspergillosis. The overall incidence was 1.6 per 1,000 patient-days (95% confidence interval: 1.4, 1.9) with a decrease of 16% per year (-1%, -28%). The incidence was 1.9 per 1,000 patient-days (1.5, 2.3) in acute myeloid leukemia patients with a decrease of 20% per year (-6%, -36%). Serum Aspergillus antigen was detected in 89 (71%) patients; 29 (23%) had positive cultures, and 118 (93%), abnormal lung CT scans. One-month mortality was 13%; 3-month mortality was 42%. Mortality tended to decrease between 2004 and 2009.
Invasive aspergillosis incidence and mortality declined between 2004 and 2009. Knowledge of invasive aspergillosis characteristics and its clinical course should help to improve the management of these patients with severe disease.
Haematologica 07/2011; 96(11):1685-91. · 6.42 Impact Factor
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ABSTRACT: Mechanisms concerning life or death decisions in protozoan parasites are still imperfectly understood. Comparison with higher eukaryotes has led to the hypothesis that caspase-like enzymes could be involved in death pathways. This hypothesis was reinforced by the description of caspase-related sequences in the genome of several parasites, including Plasmodium, Trypanosoma and Leishmania. Although several teams are working to decipher the exact role of metacaspases in protozoan parasites, partial, conflicting or negative results have been obtained with respect to the relationship between protozoan metacaspases and cell death. The aim of this paper is to review current knowledge of protozoan parasite metacaspases within a drug targeting perspective.
Parasites & Vectors 02/2011; 4:26. · 2.94 Impact Factor
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ABSTRACT: Invasive aspergillosis (IA) is an important cause of morbidity and mortality in neutropenic patients with hematological malignancies. To investigate the immediate and mid-term benefits of posaconazole prophylaxis in AML patients undergoing first induction chemotherapy and to study the infection risk factors, we prospectively studied the IA incidence in these patients at our hospital between years 2007 and 2008; then we compared them to a matched control group without prophylaxis. There were 55 and 66 patients in each group respectively. At day 32 post-induction, two probable cases (3.6%) were scored in the prophylaxis group compared to 8 cases (12.1%) in the control group (4 possible and 4 probable). At day 100, it reached 7.27% and 15.5% respectively. Kaplan-Meier analysis at day 100 showed lower mortality rate in the prophylaxis group compared to the control group [3.64% (n = 2, none due to IA) and 10.61% (n = 7, four due to IA) respectively, P = 0.002]. Multivariate analysis showed age and lack of response to induction as independent infection risk factors. Posaconazole prophylaxis resulted in lower incidence of IA and significantly improved survival. Patient's age and response to induction treatment are two independent infection risk factors, and need more attention during future clinical trials linked to antifungal prophylaxis.
Medical mycology: official publication of the International Society for Human and Animal Mycology 02/2011; 49(7):681-7. · 2.13 Impact Factor
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ABSTRACT: Fatalities caused by parasitic infections often occur as a result of tissue injury that results from a form of host-cell death known as apoptosis. However, instead of being pathogenic, parasite-induced apoptosis may facilitate host survival. Consequently, it is of utmost importance to decipher and understand the process and the role of apoptosis induced or controlled by parasites in humans. Despite this, few studies provide definitive knowledge of parasite-induced host-cell apoptosis. Here, the focus is on a consideration of host-cell apoptosis as either a pathogenic feature or as a factor enabling parasite survival and development.Cell death by apoptotic-like mechanisms could be described as a ride to death with a return ticket, as initiation of the pathway may be reversed, with the potential that it could be manipulated for therapeutic purposes. The management of host-cell apoptosis could thus be an adjunctive factor for parasitic disease treatment. Evidence that the apoptotic process could be reversed by anti-apoptotic drugs has recently been obtained, leading to the possibility of host-cell rescue after injury. An important issue will be to predict the beneficial or deleterious effects of controlling human cell death by apoptotic-like mechanisms during parasitic diseases.
Parasites & Vectors 11/2010; 3:106. · 2.94 Impact Factor
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Journal of clinical gastroenterology 03/2010; 44(8):593-4. · 2.21 Impact Factor
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ABSTRACT: Cerebral malaria carries an unacceptable case fatality rate in children despite timely and adequate chemotherapy. To improve the survival rate, adjunctive therapies previously tested mainly focused on the modulation of the inflammatory response, without definitive effect in humans. In this context, a new adjunctive strategy using a neuroprotective drug: erythropoietin (epoietin-beta, Epo) was proposed.
An open-labelled study including cerebral malaria children (Blantyre coma score below 3) was conducted in Mali. The objective was to assess the short-term safety (seven days) of erythropoietin at high doses (1,500 U/kg/day during three days) combined to quinine.
35 patients with unrousable coma were included in the study. None of expected side effects of erythropoietin were observed during the seven days follow-up. No significant increase in the case fatality rate (7/35 patients) was observed compared to other studies with mortality rates ranging from 16 to 22% in similar endemic areas.
These data provide the first evidence of the short-term safety of erythropoietin at high doses combined to quinine. A multicentre study is needed to assess the potential of Epo as an adjunctive therapy to increase the survival during cerebral malaria. CLINICAL REGISTRATION NUMBER: ClinicalTrials.gov ID: NCT00697164.
Malaria Journal 08/2009; 8:169. · 3.19 Impact Factor
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ABSTRACT: Bisphenol A (BPA) is widely used in the manufacturing of polycarbonate plastic food and drink packaging. Possessing a weak estrogenic activity, BPA is listed among a growing list of endocrine disrupting compounds. In this study, a polyclonal anti-BPA antibody was obtained by immunization with BPA-monocarboxymethylether covalently linked to BSA. The antibody demonstrates negligible cross-reactivity with most analogous BPA phenolic structures, and no cross-reactivity with endogenous steroids. An extraction step with ethyl acetate minimized matrix effects and allowed the BPA measurement in plasma and other biological samples. Recovery after loading test was 96 +/- 4% and dilution tests had a linear profile (r2 > 0.93). The limit of detection of the BPA RIA was 0.08 microg L(-1) with an IC50 of 1.25 microg L(-1). The intra- and inter-assay coefficients of variation were 5.6 and 8.6%, respectively at a BPA concentration of 0.7 microg L(-1) and 6.9 and 5.7% at a BPA concentration of 1.3 microg L(-1). A significant correlation was found between the values obtained by the RIA and HPLC-MS (r2 = 0.92) or HPLC coupled to a fluorescence detector (r2 = 0.80). In conclusion, we described a BPA-RIA that is a suitable tool for evaluating human exposure to BPA.
Analytica chimica acta 07/2009; 645(1-2):1-4. · 4.31 Impact Factor
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ABSTRACT: An assessment of the correlation between anti-malarial treatment outcome and molecular markers would improve the early detection and monitoring of drug resistance by Plasmodium falciparum. The purpose of this systematic review was to determine the risk of treatment failure associated with specific polymorphisms in the parasite genome or gene copy number.
Clinical studies of non-severe malaria reporting on target genetic markers (SNPs for pfmdr1, pfcrt, dhfr, dhps, gene copy number for pfmdr1) providing complete information on inclusion criteria, outcome, follow up and genotyping, were included. Three investigators independently extracted data from articles. Results were stratified by gene, codon, drug and duration of follow-up. For each study and aggregate data the random effect odds ratio (OR) with 95%CIs was estimated and presented as Forest plots. An OR with a lower 95th confidence interval > 1 was considered consistent with a failure being associated to a given gene mutation.
92 studies were eligible among the selection from computerized search, with information on pfcrt (25/159 studies), pfmdr1 (29/236 studies), dhfr (18/373 studies), dhps (20/195 studies). The risk of therapeutic failure after chloroquine was increased by the presence of pfcrt K76T (Day 28, OR = 7.2 [95%CI: 4.5-11.5]), pfmdr1 N86Y was associated with both chloroquine (Day 28, OR = 1.8 [95%CI: 1.3-2.4]) and amodiaquine failures (OR = 5.4 [95%CI: 2.6-11.3, p < 0.001]). For sulphadoxine-pyrimethamine the dhfr single (S108N) (Day 28, OR = 3.5 [95%CI: 1.9-6.3]) and triple mutants (S108N, N51I, C59R) (Day 28, OR = 3.1 [95%CI: 2.0-4.9]) and dhfr-dhps quintuple mutants (Day 28, OR = 5.2 [95%CI: 3.2-8.8]) also increased the risk of treatment failure. Increased pfmdr1 copy number was correlated with treatment failure following mefloquine (OR = 8.6 [95%CI: 3.3-22.9]).
When applying the selection procedure for comparative analysis, few studies fulfilled all inclusion criteria compared to the large number of papers identified, but heterogeneity was limited. Genetic molecular markers were related to an increased risk of therapeutic failure. Guidelines are discussed and a checklist for further studies is proposed.
Malaria Journal 01/2009; 8:89. · 3.19 Impact Factor
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ABSTRACT: Statins are a family of lipid-lowering drugs widely used to control cholesterol level and to prevent stroke and cardiac failure in patients at high risk of coronary artery disease. ...
Antimicrobial Agents and Chemotherapy 10/2008; 52(11):4203-4. · 4.84 Impact Factor
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ABSTRACT: Cerebral malaria is the most severe and rapidly fatal complication of Plasmodium falciparum infection. Despite appropriate anti-malarial treatment using quinine or artemisinin derivatives, 10-20% of mortality still occurs during the acute phase. To improve cerebral malaria outcome, adjunctive therapies are clearly needed. Most experiments in this area have been dedicated to immuno-modulation with various successes. Since erythropoietin has been shown to be highly effective in human ischemic stroke and in murine cerebral malaria, we addressed the issue of cerebral malaria outcome improvement by erythropoietin-artesunate drug combination. Compared to the previous study using erythropoietin high doses at the early beginning of the disease, erythropoietin treatment was decreased by six-fold and delayed to the pre-mortem phase. We studied effects on survival and on clinical recovery of the drug combination given from day 6 to day 8 post-infection to CBA/J mice infected by Plasmodium berghei ANKA. We showed that the artesunate-erythropoietin drug combination led to clinical recovery 24 h earlier for surviving mice, and to increase in the global survival rate compared to artesunate monotherapy (p<0.01). Since erythropoietin has no effect on parasite clearance, it could be stated that this drug combination is efficient and that erythropoietin could be a lead for the implementation of a new adjunctive therapy during the acute phase of cerebral malaria.
Acta Tropica 05/2008; 106(2):104-8. · 2.72 Impact Factor
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ABSTRACT: Morbidity and mortality during malaria are mostly due to Plasmodium falciparum infection. However, it becomes clear that Plasmodium vivax is responsible for a dramatic toll in many endemic areas except Africa. Cerebral malaria, severe respiratory distress and severe anaemia were recently reported from different settings, with severe disease peaking at an earlier age than those of Plasmodium falciparum. Since infected red blood cells sequestration was not reported with Plasmodium vivax infection, mechanisms at the origin of these complications are still a mater of debate. The major issue addressed in that paper is to alert clinicians on the -potential severity of this "benign tertian fever".
Medecine sciences: M/S 25(6-7):622-6. · 0.64 Impact Factor
