L’utilisation de l’approche CTC: quel impact sur la couverture vaccinale lors de la campagne préventive de vaccination contre la méningite A avec le MenAfriVac au Togo en 2014?

Introduction: Une campagne de vaccination contre la méningite A avec le vaccin MenAfriVac a été organisée dans les quatre régions septentrionales du Togo du 28 novembre au 07 décembre 2014. L'approche CTC a été utilisée pour la première fois à une grande échelle pour la campagne de vaccination dans dix districts sanitaires du Togo. L'objectif de cette étude était d'estimer la couverture vaccinale et, de déterminer l'effet de l'utilisation de la Chaîne à Température Contrôlée (CTC) sur ces couvertures vaccinales.Méthodes: L'enquête s'est déroulée du 9 au 14 mars 2015, soit environ 3 mois après la fin de la campagne de vaccination dans ces quatre régions. Le sondage en grappe à deux degrés stratifiés selon les régions a été utilisé. Dans 10 districts, le Togo a fait le choix d'utiliser le vaccin MenAfriVac en CTC.Résultats: Au total, 2707 ménages ont été enquêtés et 9082 personnes âgées de 1 à 29 ans ont été interviewées. L'âge moyen des personnes enquêtées était de 11,8±7,7 ans et le sex-ratio (H/F) de 1,01. Le nombre moyen de personnes par ménage était de 5,7 et celui des personnes de 1 à 29 ans ciblées par la campagne était de 3,4. Sur les 9082 personnes enquêtées, 8889 (98%) étaient vaccinées. En analyse multivariée, les facteurs associés à la couverture vaccinale avec le MenAfrivac étaient la résidence dans la zone au moment de la campagne (aOR = 4,52 ; 95%IC = [4.07 - 4.97]) et le fait d'être informé de la campagne avant son démarrage (aOR=2,42 ; 95%IC = [2.05 - 2.80]). Par contre, la couverture vaccinale n'était pas différente selon la zone ayant utilisé l'approche CTC ou non (aOR=0,09 ; 95%IC = [-0,27-0,45]). Deux cent sept personnes interrogées (2,3%) ont déclaré avoir eu une Manifestation Adverse Post Immunisation (MAPI) après l'administration du vaccin. Il s'agissait surtout de MAPI mineures à type de fièvre,  d'abcès et de gonflement au point d'injection.Conclusion: Les résultats de cette enquête montrent que l'utilisation de la CTC dans un pays à ressources limitées comme le Togo n'a pas eu un effet négatif sur les couvertures vaccinales. En effet, il n'y avait pas de différence entre la couverture vaccinale dans les zones CTC et celles non CTC. Il importe de capitaliser l'expérience acquise pour l'utilisation des vaccins du Programme Elargi de Vaccination avec l'approche CTC surtout dans les pays à ressources limitées confrontés à la disponibilité de la chaîne de froid.Mots clés: Meningitis A, MenAfriVac vaccine, CTC, immunization coverage, TogoEnglish Title: Impact of Controlled Temperature Chain (CTC) approach on immunization coverage achieved during the preventive vaccination campaign against meningitis A using MenAfriVac in Togo in 2014English AbstractBackground: a vaccination campaign against meningitis A using MenAfriVac vaccine was implemented in the four regions of northern Togo from 28 November to 7 December 2014. CTC approach was first used on a large scale in a vaccination campaign in ten health districts in Togo. This study aims to estimate the immunization coverage and to determine the effect of Controlled Temperature Chain (CTC) approach on these immunization coverages.Method: we conducted a survey from 9 to 14 March 2015 (for approximately 3 months) after the end of the vaccination campaign in these four regions. Interviewees were selected using two stages cluster sampling stratified according to the regions. MenAfriVac vaccine in Controlled Temperature Chain (CTC) was used in 10 districts, in Togo.Results: a total of 2707 households were surveyed and 9082 people aged 1-29 years were interviewed. The average age of the individuals surveyed was 11.8±7.7 years and sex-ratio (H/F) was 1.01. The average number of individuals per household was 5.7 and that of persons aged 1-29 years targeted in the campaign was 3.4. Out of 9082 people surveyed 8889 (98%) were vaccinated. Multivariate analysis showed that the factors associated with immunization coverage using MenAfrivac vaccine were: habitual residence in the area at the time of the campaign (AOR = 4.52; 95%CI = [4.07 - 4.97]) and level of information about the campaign before it starts (AOR=2.42; 95%CI = [2.05 - 2.80]). By contrast, there were no differences in vaccination coverage between the areas based on whether the CTC approach was used or not (AOR=0.09; 95%CI = [-0.27 - 0.45]). Two hundred and seven respondents (2.3%) reported that they had Adverse Event Following Immunisation (AEFI) after the administration of the vaccine. These were usually minor AEFI involving fever, abscesses and swelling at the injection site.Conclusion: survey results show that the use of CTC in a country with limited resources such as Togo doesn't have a negative impact on immunization coverage. Indeed, there was no difference between immunization coverage in CTC and non-CTC areas. It is important to capitalize on the experience gained in order to use vaccines by Expanded Program of Immunization in CTC approach especially in countries with limited resources in terms of cold chain availability.Keywords: Meningitis A, MenAfriVac vaccine, CTC, vaccine coverage, Tog

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old