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International audience

Summary: Purpose: Cerebral malaria (CM) is suspected to be a potential cause of epilepsy in tropical areas, but little information is available. The purpose of this study was to evaluate the role of CM in epilepsy among children in Mali. Methods: An exposed–nonexposed study was performed to identify children who had epilepsy after malaria in the 0- to 15-year age group. The exposure factor was CM defined according to World Health Organization (WHO) criteria, and the nonexposure factor was symptomatic malaria without the characteristics of CM (NCM). All the children underwent a screening questionnaire and were examined by a medical physician. After the screening phase, a specialist in neuropediatrics examined the children suspected to have epilepsy. EEG and computed tomography (CT) scans were performed in some of these patients. Results: In total, 101 subjects who had had CM and 222 who had had NCM were included. Fifty-four children (CM, 34; NCM, 20) were suspected to have epilepsy, and six were confirmed (CM, five; NCM, one). The incidence rate was 17.0 per 1000 person-years in the CM group and 1.8 per 1000 person-year in the NCM group; thus the relative risk (RR) was 9.4 [95% confidence interval (CI), 1.3–80.3; p = 0.02]. After adjustment on age and duration of follow-up, the RR was 14.3 (95% CI, 1.6–132.0; p = 0.01). Conclusions: The risk of sequelar epilepsy is significantly higher in the CM group compared with the NCM group. A reevaluation of this cohort should be carried out later to search for temporal epilepsy that appeared after age 10 years.

Background Malaria remains a major public health problem, due largely to emergence and widespread P. falciparum drug resistance. WHO recommends artemisinine combination based therapy (ACT) to overcome P. falciparum drug resistance, but reports of declining ACT efficacy have been published. A thorough understanding of the molecular bases of P. falciparum resistance to existing drugs is therefore needed. The aims of this study were to analyze the in vitro sensitivity of P. falciparum field isolates from Franceville, Gabon, to chloroquine (CQ), mefloquine (MF), dihydroartemisinine (DHA) and monodesethylamodiaquine (MDAQ), and to investigate polymorphisms associated with drug resistance. Methods We conducted a cross-sectional study of 53 field isolates. Field isolates sensitivity to CQ, MF, DHA and MDAQ was assessed using the colorimetric DELI test. The Pfmdr1 codons 86 and 1246, Pfcrt (haplotype codon 72 to 76) and the PfATPAse6 codons 110 and 2694 were analysed by PCR-RFLP. Associations between drug sensitivity and parasite gene polymorphisms were evaluated with the Chi square test, and routine hematological parameters were analyzed with Fisher’s exact test implemented with Epinfo software. In all statistical tests, significance was assumed at p Results A total of 46 P. falciparum isolates were successfully cultured in vitro and their sensitivity was tested. The proportions of isolates resistant to CQ, MF and MDAQ were 43.5%, 23.4% and 56.5%, respectively. Some isolates (23.9%) had DHA IC50 values higher than 10 nM. The median IC50 values were 71.67 (interquartile range (IQR, 1–438.2), 6.59 (IQR, 0.08-96), 64.79 (IQR, 0.09-448) and 6.45 nM (IQR, 0.09-23) for CQ, MF, MDAQ and DHA, respectively. The strongest correlation between diminished DHA sensitivity and MF resistance was observed (r2=0.73), followed by correlation between diminished DHA sensitivity and CQ resistance. Cross-resistance between CQ and MF was also observed. The prevalence of the 86Y and 1246Y mutations in Pfmdr1, 76T in Pfcrt, and 110A and 2694T in PfATPase6 was respectively 42% and 17.1%, 97.8%, and 0% and 22.2%. Conclusion These high levels of antimalarial drug resistance in Franceville, Gabon, call for reinforced surveillance of drug efficacy.

International audience

International audience; Pediatric drug formulations of artemisinin combination therapies are urgently needed for improving the treatment of children suffering from uncomplicated malaria. The aim of this clinical trial was to evaluate the efficacy, safety and tolerability of a novel pediatric fixed-dose granule formulation of artesunate-mefloquine and a new co-blister tablet formulation. A total of 71 children aged 1-13 years suffering from uncomplicated falciparum malaria were stratified into two groups according to weight: 10-20 kg, pediatric group (n = 41); 20-40 kg, tablet group (n = 30). All the children were treated once daily for three days: the pediatric group received the novel granule formulation, the tablet group received the co-blister tablets. The PCR-corrected cure rate on day 28 was evaluated. There was no reappearance of parasitemia during the follow-up period and the day-28 cure rate was therefore 100% in per-protocol analysis. In intention-to-treat analysis the cure rates were 95% in the pediatric group and 97% in the tablet group. The most frequent adverse events were vomiting (17%), abdominal pain (11%) and headache (17%). This study confirms the excellent efficacy and favorable safety and tolerability profile of a novel pediatric artesunate-mefloquine formulation for treatment in African children.

International audience; A laboratory-confirmed diagnosis is the basis of malaria case management. Rapid diagnostic tests (RDTs) create new opportunities for improved care in endemic areas. Diagnostic performance of OptiMAL-IT and Acon was assessed in comparison with microscopy at 2 sites in Gabon. Between February 2008 and January 2009, 2125 febrile children under 11 years old were diagnosed using microscopy and RDTs. Plasmodial infection was detected more frequently using Acon (27%) and OptiMAL-IT (27%) compared to microscopy (20%) (P < 0.01). Among the samples diagnosed positive by OptiMAL-IT, 78% were infected by Plasmodium falciparum, whereas 99% of positive blood smears were P. falciparum infections, 0.5% Plasmodium malariae, and 0.5% Plasmodium ovale. Both RDTs had similar sensitivity (Se) (94.0%; 95% confidence interval [CI], 92-96), which varied depending on the site. When parasite density was >100 p/microL, the Se of the 2 tests was >98% (95% CI, 96-100). Likewise, the negative predictive values were high and comparable (>98%). Overtreatment with antimalarial drugs was 12%. These tests should be considered as a good alternative to microscopy, allowing not only an efficient and rapid diagnosis of malaria in primary health facilities but also to aid in promoting changes for antimalarial prescription behavior.

Background Improving the understanding of childhood malarial anaemia may help in the design of appropriate management strategies. Methods A prospective observational study over a two-year period to assess the burden of anaemia and its relationship to Plasmodium falciparum infection and age was conducted in 8,195 febrile Gabonese children. Results The proportion of children with anaemia was 83.6% (n = 6830), higher in children between the ages of six and 23 months. Those under three years old were more likely to develop moderate to severe anaemia (68%). The prevalence of malaria was 42.7% and P. falciparum infection was more frequent in children aged 36–47 months (54.5%). The proportion of anaemic children increased with parasite density (p < 0.01). Most of infected children were moderately to severely anaemic (69.5%, p < 0.01). Infants aged from one to 11 months had a higher risk of developing severe malarial anaemia. In children over six years of age, anaemia occurrence was high (>60%), but was unrelated to P. falciparum parasitaemia. Conclusion Malaria is one of the main risk factors for childhood anaemia which represents a public health problem in Gabon. The risk of severe malarial anaemia increases up the age of three years. Efforts to improve strategies for controlling anaemia and malaria are needed.

ERMA; National audience

International audience; Malaria, one of the most common parasitic diseases worldwide, is responsible for more than one million deaths among African children every year. Its neurological form, known as cerebral malaria (CM) is a potential cause of epilepsy in malaria-endemic regions of the world, primarily made up for the most part by the sub-Saharan Africa. Herein, we review recent African studies that examine the association between CM and epilepsy. Three studies suggest a modestly strong association between CM and epilepsy. Furthermore, there appears little doubt that this association is causal. Speculative considerations that may explain this causal association are discussed in this review. Additional research is however required in order to determine the clinical and electrographic behavior, the underlying structural and molecular basis, and course and outcome of this condition.

International audience; PURPOSE: Cerebral malaria (CM) is suspected to be a potential cause of epilepsy in tropical areas, but little information is available. The purpose of this study was to evaluate the role of CM in epilepsy among children in Mali. METHODS: An exposed-nonexposed study was performed to identify children who had epilepsy after malaria in the 0- to 15-year age group. The exposure factor was CM defined according to World Health Organization (WHO) criteria, and the nonexposure factor was symptomatic malaria without the characteristics of CM (NCM). All the children underwent a screening questionnaire and were examined by a medical physician. After the screening phase, a specialist in neuropediatrics examined the children suspected to have epilepsy. EEG and computed tomography (CT) scans were performed in some of these patients. RESULTS: In total, 101 subjects who had had CM and 222 who had had NCM were included. Fifty-four children (CM, 34; NCM, 20) were suspected to have epilepsy, and six were confirmed (CM, five; NCM, one). The incidence rate was 17.0 per 1000 person-years in the CM group and 1.8 per 1000 person-year in the NCM group; thus the relative risk (RR) was 9.4 [95% confidence interval (CI), 1.3-80.3; p = 0.02]. After adjustment on age and duration of follow-up, the RR was 14.3 (95% CI, 1.6-132.0; p = 0.01). CONCLUSIONS: The risk of sequelar epilepsy is significantly higher in the CM group compared with the NCM group. A reevaluation of this cohort should be carried out later to search for temporal epilepsy that appeared after age 10 years.

Human African trypanosomiasis (HAT) or sleeping sickness is a disease characterized by a hemolymphatic stage 1 followed by a meningoencephalitic stage 2 which is fatal without specific treatment. Furthermore, due to the toxicity of drugs used to treat stage 2 (mainly melarsoprol) accurate staging is required. Actual criteria employed during field surveys are not sensitive enough for precise staging. Antineurofilament (anti-NF) and antigalactocerebrosides (anti-GalC) antibodies have been identified in cerebrospinal fluid (CSF) as potential markers of central nervous system (CNS) involvement. We describe a dot enzyme-linked immunosorbent assay (dot-ELISA) to detect anti-GalC and anti-NF antibodies and its value in staging. NF- and GalC-dotted nitrocellulose strips were first developed in our laboratory. They were then evaluated in Angola and Central African Republic on 140 CSF samples. Compared to our staging criteria (i.e., CSF cell count ≥ 20 cells/μl, CSF immunoglobulin M concentration ≥ 100 mg/liter, and/or the presence of trypanosomes in the CSF), combined detection of both CSF anti-NF and CSF anti-GalC by dot-ELISA showed 83.2% sensitivity and 100.0% specificity. Dot-ELISA could be a useful test to diagnose CNS involvement in HAT in the less-equipped laboratories or in the field situation and to improve patient treatment.

Objectif Evaluer les connaissances et attitudes des enseignants en matiere d’epilepsie de l’enfant. Materiel et methodes etude transversale menee de janvier a mai 2011, a Libreville et Owendo. Etaient inclus les instituteurs d’etablissements scolaires prives et publics, selectionnes par tirage aleatoire simple. Les connaissances generales des enseignants sur l’epilepsie, la crise d’epilepsie, et les attitudes face a une crise epileptique ont ete recueillies sur fiche standardisee. Resultats Au total, 277 enseignants dont 160 femmes (57,8%) ont ete inclus. L’âge moyen etait de 36,4 ± 6,7 ans. Pour 67,9% (n=188) des enseignants la maladie serait d’origine organique, 55,2% (n=153) evoquaient une origine mystique. L’epilepsie serait contagieuse pour 37,5% (n=105), dans 94,5% la salive serait la principale source de contagion. Les manifestations de l’epilepsie « grand mal » etait bien connues. Environ 90% des enseignants ne connaissaient ni l’epilepsie-absence, ni l’etat de mal epileptique. En cas de crise, 80% des enseignants auraient mis un objet dans la bouche. 66,1% des enseignants aimeraient recevoir une formation sur l’epilepsie. Conclusion L’epilepsie est mal connue des enseignants, d’ou la necessite d’une information adequate visant a les edifier sur cette affection.

Introduction L’epilepsie touche 50 millions de personnes dans le monde. Plus de 80 % de ces patients vivent dans les PED dont 80% ne recevraient pas un traitement adapte. Dans ces pays, 70% de la population vivent en zone rurale. Objectifs Etudier la litterature relative a la prise en charge therapeutique de l’epilepsie dans les pays en voie de developpement, en zone rurale ou vivent de nombreux patients souffrant d’epilepsie. Methodes Il s’agit d’une recherche bibliographique croisant sur Medline les mots –– cles suivants : prise en charge ; epilepsie ; antiepileptiques ; zone rurale et pays en voie de developpement. Resultats 17 articles (1989 a 2005) sur plus de 1 500 patients concernaient l’Afrique, 56 %, l’Asie, 33 %, l’Amerique, 11 %. 77 % des etudes (duree : 2-60 mois) utilisaient : carbamazepine, phenobarbital, phenytoine et/ou valproate. 65 % incluaient du phenobarbital. 76 % exploraient l’efficacite ; 29 %, les effets indesirables et 58 %, l’observance. La reponse etait « satisfaisante » (30,7 %) et, dans 30,7 %, les crises, reduites d’au moins 50 % pour 18 % des patients, tendant vers leur disparition chez 64 %. Discussion Lorsque le traitement est encadre par une etude, il s’avere efficace, quel que soit le medicament. C’est le phenobarbital qui a offert la meilleure tolerance. Il est, par ailleurs, le moins couteux. Des que l’encadrement s’arrete, la mauvaise observance s’installe, compromettant l’efficacite therapeutique. Conclusion Ces travaux montrent le benefice des antiepileptiques. Pour que ce benefice soit perenne, il faut ameliorer l’accessibilite aux traitements (possible avec le phenobarbital) et organiser une education therapeutique efficace.

Introduction De nombreuses etudes menees en Amerique latine, en Inde et en Asie montrent que la cysticercose constitue un facteur de risque majeur d’epilepsie. L’association entre cysticercose et epilepsie a ete peu etudiee en Afrique. Objectifs Quantifier l’association entre l’infection par des larves de Taenia solium et la presence d’une epilepsie a partir des donnees bibliographiques disponibles collectees en Afrique subsaharienne. Methodes Une revue de la litterature des etudes specifiques du lien entre cysticercose et epilepsie en Afrique a ete realisee dans plusieurs bases de donnees (Medline, Pascal, Uncover, Excerpta Medica, base bibliographique de l’IENT). Toutes les etudes presentant le statut individuel vis-a-vis de la cysticercose et de l’epilepsie et reposant sur une methode de diagnostic serologique sur anticorps pour la cysticercose et un diagnostic neurologique pour l’epilepsie, ont ete incluses dans une meta-analyse. Resultats Huit etudes ont ete incluses soit un total de 5 106 sujets (1 175 epileptiques dont 433 atteints de cysticercose et 398 infectes non-epileptiques). Sur l’ensemble des etudes, la cysticercose etait significativement associee a l’epilepsie (OR = 2,9 ; IC95 % : [2,2-3,9] ; p Discussion En Afrique subsaharienne, les personnes seropositives pour la cysticercose ont un risque environ 3 fois plus eleve de presenter une epilepsie. Le fait que les diagnostics de cysticercose et d’epilepsie aient generalement ete realises dans le cadre d’enquetes transversales, c’est-a-dire souvent au meme moment, rend cependant incertain la determination de l’anteriorite de la cysticercose sur l’epilepsie. Conclusion La cysticercose est fortement associee au risque de presenter une epilepsie en Afrique subsaharienne. Un controle efficace de la cysticercose permettrait de limiter l’incidence de l’epilepsie.

Background Substantial decline in malaria transmission, morbidity and mortality has been reported in several countries where new malaria control strategies have been implemented. In Gabon, the national malaria policy changed in 2003, according to the WHO recommendations. The trend in malaria morbidity was evaluated among febrile children before and after their implementation in Libreville, the capital city of Gabon. Methods From August 2000 to December 2008, febrile paediatric outpatients and inpatients, under 11 years of age, were screened for malaria by microscopic examination at the Malaria Clinical Research Unit (MCRU) located in the largest public hospital in Gabon. Climatic data were also collected. Results In total, 28,092 febrile children were examined; those under five years always represented more than 70%. The proportion of malaria-positive slides was 45% in 2000, and declined to 15% in 2008. The median age of children with a positive blood smear increased from 24(15-48) to 41(21-72) months over the study period (p < 0.01). Rainfall patterns had no impact on the decline observed throughout the study period. Conclusion The decrease of malaria prevalence among febrile children during the last nine years is observed following the introduction of new strategies of malaria cases management, and may announce epidemiological changes. Moreover, preventive measures must be extended to children older than five years.

Background In Gabon, following the adoption of amodiaquine/artesunate combination (AQ/AS) as first-line treatment of malaria and of sulphadoxine/pyrimethamine (SP) for preventive intermittent treatment of pregnant women, a clinical trial of SP versus AQ was conducted in a sub-urban area. This is the first study carried out in Gabon following the WHO guidelines. Methods A random comparison of the efficacy of AQ (10 mg/kg/day × 3 d) and a single dose of SP (25 mg/kg of sulphadoxine/1.25 mg/kg of pyrimethamine) was performed in children under five years of age, with uncomplicated falciparum malaria, using the 28-day WHO therapeutic efficacy test. In addition, molecular genotyping was performed to distinguish recrudescence from reinfection and to determine the frequency of the dhps K540E mutation, as a molecular marker to predict SP-treatment failure. Results The day-28 PCR-adjusted treatment failures for SP and AQ were 11.6% (8/69; 95% IC: 5.5–22.1) and 28.2% (20/71; 95% CI: 17.7–38.7), respectively This indicated that SP was significantly superior to AQ (P = 0.019) in the treatment of uncomplicated childhood malaria and for preventing recurrent infections. Both treatments were safe and well-tolerated, with no serious adverse reactions recorded. The dhps K540E mutation was not found among the 76 parasite isolates tested. Conclusion The level of AQ-resistance observed in the present study may compromise efficacy and duration of use of the AQ/AS combination, the new first-line malaria treatment. Gabonese policy-makers need to plan country-wide and close surveillance of AQ/AS efficacy to determine whether, and for how long, these new recommendations for the treatment of uncomplicated malaria remain valid.