Manifestations electro-cliniques du syndrome de Lennox–Gastaut

Introduction : Le syndrome de Lennox-Gastaut (SLG) est une encéphalopathie épileptique rare. Notre étude consiste à déterminer les caractéristiques électro-cliniques du SLG au centre hospitalier national universitaire de Fann à DAKAR. Méthodologie: Il s’agit d’une étude rétrospective portant sur les dossiers médicaux de juillet 2004 à mai 2015, réalisée à la clinique neurologique et à l’hôpital des enfants Albert Royer. L’âge des enfants, l’âge de début des crises, les antécédents pathologiques, le type de crise, les troubles cognitifs et les tracés EEG ont été recueillis. Ont été inclus dans cette étude, tous les patients présentant de multiples types de crises, partielles ou généralisées ; un retard mental et à l’EEG, des pointes ondes lentes généralisées à la veille et/ou pointes rapides rythmiques pendant le sommeil.Résultats: Nous rapportons cinq cas de SLG de différents âges avec comme antécédents, une épilepsie familiale chez trois enfants et un syndrome de west chez un enfant. Le sex ratio était de 3/2 en faveur du sexe masculin. L’âge de début du SLG se situait typiquement entre 1 et 7 ans chez 4 patients. Les types de crises retrouvées étaient les crises toniques (100%), les absences atypiques (80%), les crises partielles motrices (60%), les crises atoniques (40%) et crises généralisées tonico-cloniques (40%). Aussi, tous les enfants avaient des troubles cognitifs. Les patterns EEG les plus fréquemment retrouvés étaient des décharges de Pointes ondes lentes Conclusion : Le SLG est une encéphalopathie épileptique infantile rare caractérisée par de multiples types de crise, un tracé EEG spécifique et un retard psychomoteur. Les résultats de notre étude concernant le profil électro-clinique se rapprochent de ceux de la littérature. Electro-clinical manifestations of Lennox–Gastaut SyndromeIntroduction: Lennox–Gastaut syndrome (LGS) is an uncommon epileptic encephalopathy. In this study, we tried to determine the clinical and EEG characteristics of patients with LGS in DAKAR Fann teaching hospital. Methods: It is a retrospective study concerning medical folders during July 2004 to May 2015 realized in neurological clinic and Albert Royer children’s hospital. Age, gender, age at seizure onset, seizure type(s), epilepsy risk factors, cognitive disorders and EEG of all patients were registered. We included for this study all patients presenting multiple seizure types, mental retardation and an interictal EEG showing bursts of slow spike-wave complexes during awake and/or generalized paroxysmal fast activity during sleep. Results: We report different age five LGS cases with familial epilepsia in three cases and west syndrome in one case. The sex ratio was 3/2 for male. The age at seizure onset was typically between 1 and 7 years in four patients. The most common seizure type was tonic (100%), followed by atypic absence (80%), partial motor seizures (60%), and atonic seizures (40%) and generalized tonic–clonic seizures (40%). All the five childrens had cognitive disorders. The most common EEG finding was slow spike-wave complexes. Conclusion: LGS is an uncommon epileptic encephalopathy characterized by multiple seizure types, a specific electroencephalographic pattern and psychomotor retardation, beginning in childhood. Our results are  comparable with literature.

Effect of a mass radio campaign on family behaviours and child survival in Burkina Faso: a repeated cross-sectional, cluster-randomised trial.

BACKGROUND: Media campaigns can potentially reach a large audience at relatively low cost but, to our knowledge, no randomised controlled trials have assessed their effect on a health outcome in a low-income country. We aimed to assess the effect of a radio campaign addressing family behaviours on all-cause post-neonatal under-5 child mortality in rural Burkina Faso. METHODS: In this repeated cross-sectional, cluster randomised trial, clusters (distinct geographical areas in rural Burkina Faso with at least 40 000 inhabitants) were selected by Development Media International based on their high radio listenership (>60% of women listening to the radio in the past week) and minimum distances between radio stations to exclude population-level contamination. Clusters were randomly allocated to receive the intervention (a comprehensive radio campaign) or control group (no radio media campaign). Household surveys were performed at baseline (from December, 2011, to February, 2012), midline (in November, 2013, and after 20 months of campaigning), and endline (from November, 2014, to March, 2015, after 32 months of campaigning). Primary analyses were done on an intention-to-treat basis, based on cluster-level summaries and adjusted for imbalances between groups at baseline. The primary outcome was all-cause post-neonatal under-5 child mortality. The trial was designed to detect a 20% reduction in the primary outcome with a power of 80%. Routine data from health facilities were also analysed for evidence of changes in use and these data had high statistical power. The indicators measured were new antenatal care attendances, facility deliveries, and under-5 consultations. This trial is registered with ClinicalTrial.gov, number NCT01517230. FINDINGS: The intervention ran from March, 2012, to January, 2015. 14 clusters were selected and randomly assigned to the intervention group (n=7) or the control group (n=7). The average number of villages included per cluster was 34 in the control group and 29 in the intervention group. 2269 (82%) of 2784 women in the intervention group reported recognising the campaign's radio spots at endline. Post-neonatal under-5 child mortality decreased from 93·3 to 58·5 per 1000 livebirths in the control group and from 125·1 to 85·1 per 1000 livebirths in the intervention group. There was no evidence of an intervention effect (risk ratio 1·00, 95% CI 0·82-1·22; p>0·999). In the first year of the intervention, under-5 consultations increased from 68 681 to 83 022 in the control group and from 79 852 to 111 758 in the intervention group. The intervention effect using interrupted time-series analysis was 35% (95% CI 20-51; p<0·0001). New antenatal care attendances decreased from 13 129 to 12 997 in the control group and increased from 19 658 to 20 202 in the intervention group in the first year (intervention effect 6%, 95% CI 2-10; p=0·004). Deliveries in health facilities decreased from 10 598 to 10 533 in the control group and increased from 12 155 to 12 902 in the intervention group in the first year (intervention effect 7%, 95% CI 2-11; p=0·004). INTERPRETATION: A comprehensive radio campaign had no detectable effect on child mortality. Substantial decreases in child mortality were observed in both groups over the intervention period, reducing our ability to detect an effect. This, nevertheless, represents the first randomised controlled trial to show that mass media alone can change health-seeking behaviours. FUNDING: Wellcome Trust and Planet Wheeler Foundation

Modelling the effect of a mass radio campaign on child mortality using facility utilisation data and the Lives Saved Tool (LiST): findings from a cluster randomised trial in Burkina Faso.

BACKGROUND: A cluster randomised trial (CRT) in Burkina Faso was the first to demonstrate that a radio campaign increased health-seeking behaviours, specifically antenatal care attendance, health facility deliveries and primary care consultations for children under 5 years. METHODS: Under-five consultation data by diagnosis was obtained from primary health facilities in trial clusters, from January 2011 to December 2014. Interrupted time-series analyses were conducted to assess the intervention effect by time period on under-five consultations for separate diagnosis categories that were targeted by the media campaign. The Lives Saved Tool was used to estimate the number of under-five lives saved and the per cent reduction in child mortality that might have resulted from increased health service utilisation. Scenarios were generated to estimate the effect of the intervention in the CRT study areas, as well as a national scale-up in Burkina Faso and future scale-up scenarios for national media campaigns in five African countries from 2018 to 2020. RESULTS: Consultations for malaria symptoms increased by 56% in the first year (95% CI 30% to 88%; p<0.001) of the campaign, 37% in the second year (95% CI 12% to 69%; p=0.003) and 35% in the third year (95% CI 9% to 67%; p=0.006) relative to the increase in the control arm. Consultations for lower respiratory infections increased by 39% in the first year of the campaign (95% CI 22% to 58%; p<0.001), 25% in the second (95% CI 5% to 49%; p=0.010) and 11% in the third year (95% CI -20% to 54%; p=0.525). Diarrhoea consultations increased by 73% in the first year (95% CI 42% to 110%; p<0.001), 60% in the second (95% CI 12% to 129%; p=0.010) and 107% in the third year (95% CI 43% to 200%; p<0.001). Consultations for other diagnoses that were not targeted by the radio campaign did not differ between intervention and control arms. The estimated reduction in under-five mortality attributable to the radio intervention was 9.7% in the first year (uncertainty range: 5.1%-15.1%), 5.7% in the second year and 5.5% in the third year. The estimated number of under-five lives saved in the intervention zones during the trial was 2967 (range: 1110-5741). If scaled up nationally, the estimated reduction in under-five mortality would have been similar (9.2% in year 1, 5.6% in year 2 and 5.5% in year 3), equating to 14 888 under-five lives saved (range: 4832-30 432). The estimated number of lives that could be saved by implementing national media campaigns in other low-income settings ranged from 7205 in Burundi to 21 443 in Mozambique. CONCLUSION: Evidence from a CRT shows that a child health radio campaign increased under-five consultations at primary health centres for malaria, pneumonia and diarrhoea (the leading causes of postneonatal child mortality in Burkina Faso) and resulted in an estimated 7.1% average reduction in under-five mortality per year. These findings suggest important reductions in under-five mortality can be achieved by mass media alone, particularly when conducted at national scale

An analysis of timing and frequency of malaria infection during pregnancy in relation to the risk of low birth weight, anaemia and perinatal mortality in Burkina Faso.

BACKGROUND: A prospective study aiming at assessing the effect of adding a third dose sulphadoxine-pyrimethamine (SP) to the standard two-dose intermittent preventive treatment for pregnant women was carried out in Hounde, Burkina Faso, between March 2006 and July 2008. Pregnant women were identified as earlier as possible during pregnancy through a network of home visitors, referred to the health facilities for inclusion and followed up until delivery. METHODS: Study participants were enrolled at antenatal care (ANC) visits and randomized to receive either two or three doses of SP at the appropriate time. Women were visited daily and a blood slide was collected when there was fever (body temperature > 37.5°C) or history of fever. Women were encouraged to attend ANC and deliver in the health centre, where the new-born was examined and weighed. The timing and frequency of malaria infection was analysed in relation to the risk of low birth weight, maternal anaemia and perinatal mortality. RESULTS: Data on birth weight and haemoglobin were available for 1,034 women. The incidence of malaria infections was significantly lower in women having received three instead of two doses of SP. Occurrence of first malaria infection during the first or second trimester was associated with a higher risk of low birth weight: incidence rate ratios of 3.56 (p < 0.001) and 1.72 (p = 0.034), respectively. After adjusting for possible confounding factors, the risk remained significantly higher for the infection in the first trimester of pregnancy (adjusted incidence rate ratio = 2.07, p = 0.002). The risk of maternal anaemia and perinatal mortality was not associated with the timing of first malaria infection. CONCLUSION: Malaria infection during first trimester of pregnancy is associated to a higher risk of low birth weight. Women should be encouraged to use long-lasting insecticidal nets before and throughout their pregnancy

Major reduction of malaria morbidity with combined vitamin A and zinc supplementation in young children in Burkina Faso: a randomized double blind trial

BACKGROUND: Vitamin A and zinc are crucial for normal immune function, and may play a synergistic role for reducing the risk of infection including malaria caused by Plasmodium falciparum. METHODS: A randomized, double-blind, placebo-controlled trial of a single dose of 200 000 IU of vitamin A with daily zinc supplementation was done in children of Sourkoudougou village, Burkina Faso. Children aged from 6 to 72 months were randomized to receive a single dose of 200 000 IU of vitamin A plus 10 mg elemental zinc, six days a week (n = 74) or placebo (n = 74) for a period of six months. Cross-sectional surveys were conducted at the beginning and the end of the study, and children were evaluated daily for fever. Microscopic examination of blood smear was done in the case of fever (temperature > or =37.5 degrees C) for malaria parasite detection. RESULTS: At the end of the study we observed a significant decrease in the prevalence malaria in the supplemented group (34%) compared to the placebo group (3.5%) (p < 0.001). Malaria episodes were lower in the supplemented group (p = 0.029), with a 30.2% reduction of malaria cases (p = 0.025). Time to first malaria episode was longer in the supplemented group (p = 0.015). The supplemented group also had 22% fewer fever episodes than the placebo group (p = 0.030). CONCLUSION: These results suggest that combined vitamin A plus zinc supplementation reduces the risk of fever and clinical malaria episodes among children, and thus may play a key role in malaria control strategies for children in Africa

Efficacy and immunogenicity of R21/Matrix-M vaccine against clinical malaria after 2 years' follow-up in children in Burkina Faso: a phase 1/2b randomised controlled trial

BACKGROUND: Malaria is a leading cause of morbidity and mortality worldwide. We previously reported the efficacy of the R21/Matrix-M malaria vaccine, which reached the WHO-specified goal of 75% or greater efficacy over 12 months in the target population of African children. Here, we report the safety, immunogenicity, and efficacy results at 12 months following administration of a booster vaccination. METHODS: This double-blind phase 1/2b randomised controlled trial was done in children aged 5-17 months in Nanoro, Burkina Faso. Eligible children were enrolled and randomly assigned (1:1:1) to receive three vaccinations of either 5 μg R21/25 μg Matrix-M, 5 μg R21/50 μg Matrix-M, or a control vaccine (the Rabivax-S rabies vaccine) before the malaria season, with a booster dose 12 months later. Children were eligible for inclusion if written informed consent could be provided by a parent or guardian. Exclusion criteria included any existing clinically significant comorbidity or receipt of other investigational products. A random allocation list was generated by an independent statistician by use of block randomisation with variable block sizes. A research assistant from the University of Oxford, independent of the trial team, prepared sealed envelopes using this list, which was then provided to the study pharmacists to assign participants. All vaccines were prepared by the study pharmacists by use of the same type of syringe, and the contents were covered with an opaque label. Vaccine safety, efficacy, and a potential correlate of efficacy with immunogenicity, measured as anti-NANP antibody titres, were evaluated over 1 year following the first booster vaccination. The population in which the efficacy analyses were done comprised all participants who received the primary series of vaccinations and a booster vaccination. Participants were excluded from the efficacy analysis if they withdrew from the trial within the first 2 weeks of receiving the booster vaccine. This trial is registered with ClinicalTrials.gov (NCT03896724), and is continuing for a further 2 years to assess both the potential value of additional booster vaccine doses and longer-term safety. FINDINGS: Between June 2, and July 2, 2020, 409 children returned to receive a booster vaccine. Each child received the same vaccination for the booster as they received in the primary series of vaccinations; 132 participants received 5 μg R21 adjuvanted with 25 μg Matrix-M, 137 received 5 μg R21 adjuvanted with 50 μg Matrix-M, and 140 received the control vaccine. R21/Matrix-M had a favourable safety profile and was well tolerated. Vaccine efficacy remained high in the high adjuvant dose (50 μg) group, similar to previous findings at 1 year after the primary series of vaccinations. Following the booster vaccination, 67 (51%) of 132 children who received R21/Matrix-M with low-dose adjuvant, 54 (39%) of 137 children who received R21/Matrix-M with high-dose adjuvant, and 121 (86%) of 140 children who received the rabies vaccine developed clinical malaria by 12 months. Vaccine efficacy was 71% (95% CI 60 to 78) in the low-dose adjuvant group and 80% (72 to 85) in the high-dose adjuvant group. In the high-dose adjuvant group, vaccine efficacy against multiple episodes of malaria was 78% (95% CI 71 to 83), and 2285 (95% CI 1911 to 2568) cases of malaria were averted per 1000 child-years at risk among vaccinated children in the second year of follow-up. Among these participants, at 28 days following their last R21/Matrix-M vaccination, titres of malaria-specific anti-NANP antibodies correlated positively with protection against malaria in both the first year of follow-up (Spearman's ρ -0·32 [95% CI -0·45 to -0·19]; p=0·0001) and second year of follow-up (-0·20 [-0·34 to -0·06]; p=0·02). INTERPRETATION: A booster dose of R21/Matrix-M at 1 year following the primary three-dose regimen maintained high efficacy against first and multiple episodes of clinical malaria. Furthermore, the booster vaccine induced antibody concentrations that correlated with vaccine efficacy. The trial is ongoing to assess long-term follow-up of these participants and the value of further booster vaccinations. FUNDING: European and Developing Countries Clinical Trials Partnership 2 (EDCTP2), Wellcome Trust, and NIHR Oxford Biomedical Research Centre. TRANSLATION: For the French translation of the abstract see Supplementary Materials section

Efficacy of a low-dose candidate malaria vaccine, R21 in adjuvant Matrix-M, with seasonal administration to children in Burkina Faso: a randomised controlled trial.

BACKGROUND: Stalled progress in controlling Plasmodium falciparum malaria highlights the need for an effective and deployable vaccine. RTS,S/AS01, the most effective malaria vaccine candidate to date, demonstrated 56% efficacy over 12 months in African children. We therefore assessed a new candidate vaccine for safety and efficacy. METHODS: In this double-blind, randomised, controlled, phase 2b trial, the low-dose circumsporozoite protein-based vaccine R21, with two different doses of adjuvant Matrix-M (MM), was given to children aged 5-17 months in Nanoro, Burkina Faso-a highly seasonal malaria transmission setting. Three vaccinations were administered at 4-week intervals before the malaria season, with a fourth dose 1 year later. All vaccines were administered intramuscularly into the thigh. Group 1 received 5 μg R21 plus 25 μg MM, group 2 received 5 μg R21 plus 50 μg MM, and group 3, the control group, received rabies vaccinations. Children were randomly assigned (1:1:1) to groups 1-3. An independent statistician generated a random allocation list, using block randomisation with variable block sizes, which was used to assign participants. Participants, their families, and the local study team were all masked to group allocation. Only the pharmacists preparing the vaccine were unmasked to group allocation. Vaccine safety, immunogenicity, and efficacy were evaluated over 1 year. The primary objective assessed protective efficacy of R21 plus MM (R21/MM) from 14 days after the third vaccination to 6 months. Primary analyses of vaccine efficacy were based on a modified intention-to-treat population, which included all participants who received three vaccinations, allowing for inclusion of participants who received the wrong vaccine at any timepoint. This trial is registered with ClinicalTrials.gov, NCT03896724. FINDINGS: From May 7 to June 13, 2019, 498 children aged 5-17 months were screened, and 48 were excluded. 450 children were enrolled and received at least one vaccination. 150 children were allocated to group 1, 150 children were allocated to group 2, and 150 children were allocated to group 3. The final vaccination of the primary series was administered on Aug 7, 2019. R21/MM had a favourable safety profile and was well tolerated. The majority of adverse events were mild, with the most common event being fever. None of the seven serious adverse events were attributed to the vaccine. At the 6-month primary efficacy analysis, 43 (29%) of 146 participants in group 1, 38 (26%) of 146 participants in group 2, and 105 (71%) of 147 participants in group 3 developed clinical malaria. Vaccine efficacy was 74% (95% CI 63-82) in group 1 and 77% (67-84) in group 2 at 6 months. At 1 year, vaccine efficacy remained high, at 77% (67-84) in group 1. Participants vaccinated with R21/MM showed high titres of malaria-specific anti-Asn-Ala-Asn-Pro (NANP) antibodies 28 days after the third vaccination, which were almost doubled with the higher adjuvant dose. Titres waned but were boosted to levels similar to peak titres after the primary series of vaccinations after a fourth dose administered 1 year later. INTERPRETATION: R21/MM appears safe and very immunogenic in African children, and shows promising high-level efficacy. FUNDING: The European & Developing Countries Clinical Trials Partnership, Wellcome Trust, and National Institute for Health Research Oxford Biomedical Research Centre

Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardiometabolic risk factors from 1980 to 2010: A comparative risk assessment

Background: High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic risk factors for all countries and regions from 1980 to 2010. Methods: We used data for exposure to risk factors by country, age group, and sex from pooled analyses of population-based health surveys. We obtained relative risks for the effects of risk factors on cause-specific mortality from meta-analyses of large prospective studies. We calculated the population attributable fractions for each risk factor alone, and for the combination of all risk factors, accounting for multicausality and for mediation of the effects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specific population attributable fractions by the number of disease-specific deaths. We obtained cause-specific mortality from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all the inputs to the final estimates. Findings: In 2010, high blood pressure was the leading risk factor for deaths due to cardiovascular diseases, chronic kidney disease, and diabetes in every region, causing more than 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths, and high cholesterol for more than 10%. After accounting for multicausality, 63% (10·8 million deaths, 95% CI 10·1-11·5) of deaths from these diseases in 2010 were attributable to the combined effect of these four metabolic risk factors, compared with 67% (7·1 million deaths, 6·6-7·6) in 1980. The mortality burden of high BMI and glucose nearly doubled from 1980 to 2010. At the country level, age-standardised death rates from these diseases attributable to the combined effects of these four risk factors surpassed 925 deaths per 100 000 for men in Belarus, Kazakhstan, and Mongolia, but were less than 130 deaths per 100 000 for women and less than 200 for men in some high-income countries including Australia, Canada, France, Japan, the Netherlands, Singapore, South Korea, and Spain. Interpretation: The salient features of the cardiometabolic disease and risk factor epidemic at the beginning of the 21st century are high blood pressure and an increasing effect of obesity and diabetes. The mortality burden of cardiometabolic risk factors has shifted from high-income to low-income and middle-income countries. Lowering cardiometabolic risks through dietary, behavioural, and pharmacological interventions should be a part of the global response to non-communicable diseases. Funding: UK Medical Research Council, US National Institutes of Health. © 2014 Elsevier Ltd