Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Prevalence and Factors Associated with Late First Antenatal Care Visit in Kaya Health District, Burkina Faso

Early first antenatal consultation during pregnancy is important to identify women at risk of complications and to increase the probability of  institutional delivery, with skilled birth attendants. However, most women in developing countries begin their antenatal visits after the first  trimester. The purpose of this study was to estimate the extent of this phenomenon and to identify its main associated factors. We conducted a secondary data analysis using Kaya Health and Demographic Surveillance System Data (Kaya HDSS), which was collected between February 1st, 2013 and January 31st, 2014. This study included 704 women of reproductive age who permanently reside on Kaya HDSS area. The dependent variable was the time until the first antenatal consultation. The factors associated with late first antenatal consultation were identified by logistic regression. The prevalence of late first antenatal consultation was 62.93%. The multivariate analysis demonstrated that women of age 25 and over (OR=1.77; p=0.002), multiparity (OR=1.72; p=0.036), the women‘s lack of education (OR=2.72; p=0.001) and the household‘s poor socioeconomic level (very low: OR=2.89; p<0.001) were factors associated with late first antenatal consultation. Sanitary education, community implication and free healthcare for mothers and children can contribute in reducing this phenomenon in our context. Keywords: Antenatal care; Late initiation; Associated factors; Burkina Fas

Asymptomatic Malaria Carriage in South-Western Burkina Faso: An Epidemiological Analysis

Background: Burkina Faso is challenged by rise in malaria incidence and insecticide and drug resistance. We investigated the prevalence of asymptomatic infection of Plasmodium falciparum. over three surveys. Subjects dan Method: We conducted repeated cross-sectional surveys in September and December 2016 and June 2017 in Diebougou health district. An initial census identified 4,028 subjects aged 6 months to 18 years. The independent variables included the age or date of birth, dependant were the area of residence, the use of bed nets, presence of not of parasites, the period of the surveys and the presence or absence of clinical signs/symptoms/fever, the gender. We used electronic case report forms for data collection, then uploaded into electronic tablets PCs, transferred to a central server. Data were analyzed with R version 3.4.3 software. Baseline chara

Spatio-temporal analysis and prediction of malaria cases using remote sensing meteorological data in Diébougou health district, Burkina Faso, 2016–2017

International audienceMalaria control and prevention programs are more efficient and cost-effective when they target hotspots or select the best periods of year to implement interventions. This study aimed to identify the spatial distribution of malaria hotspots at the village level in Diébougou health district, Burkina Faso, and to model the temporal dynamics of malaria cases as a function of meteorological conditions and of the distance between villages and health centres (HCs). Case data for 27 villages were collected in 13 HCs. Meteorological data were obtained through remote sensing. Two synthetic meteorological indicators (SMIs) were created to summarize meteorological variables. Spatial hotspots were detected using the Kulldorf scanning method. A General Additive Model was used to determine the time lag between cases and SMIs and to evaluate the effect of SMIs and distance to HC on the temporal evolution of malaria cases. The multivariate model was fitted with data from the epidemic year to predict the number of cases in the following outbreak. Overall, the incidence rate in the area was 429.13 cases per 1000 person-year with important spatial and temporal heterogeneities. Four spatial hotspots, involving 7 of the 27 villages, were detected, for an incidence rate of 854.02 cases per 1000 person-year. The hotspot with the highest risk (relative risk = 4.06) consisted of a single village, with an incidence rate of 1750.75 cases per 1000 person-years. The multivariate analysis found greater variability in incidence between HCs than between villages linked to the same HC. The time lag that generated the better predictions of cases was 9 weeks for SMI1 (positively correlated with precipitation variables) and 16 weeks for SMI2 (positively correlated with temperature variables. The prediction followed the overall pattern of the time series of reported cases and predicted the onset of the following outbreak with a precision of less than 3 weeks. This analysis of malaria cases in Diébougou health district, Burkina Faso, provides a powerful prospective method for identifying and predicting high-risk areas and high-transmission periods that could be targeted in future malaria control and prevention campaigns

Anopheles bionomics, insecticide resistance mechanisms, and malaria transmission in the Korhogo area, northern Côte d’Ivoire: a pre-intervention study

International audienceA better understanding of malaria transmission at a local scale is essential for developing and implementing effective control strategies. In the framework of a randomized controlled trial (RCT), we aimed to provide an updated description of malaria transmission in the Korhogo area, northern Côte d'Ivoire, and to obtain baseline data for the trial. We performed human landing collections (HLCs) in 26 villages in the Korhogo area during the rainy season (September-October 2016, April-May 2017) and the dry season (November-December 2016, February-March 2017). We used PCR techniques to ascertain the species of the Anopheles gambiae complex, Plasmodium falciparum sporozoite infection, and insecticide resistance mechanisms in a subset of Anopheles vectors. Anopheles gambiae s.l. was the predominant malaria vector in the Korhogo area. Overall, more vectors were collected outdoors than indoors (p < 0.001). Of the 774 An. gambiae s.l. tested in the laboratory, 89.65% were An. gambiae s.s. and 10.35% were An. coluzzii. The frequencies of the kdr allele were very high in An. gambiae s.s. but the ace-1 allele was found at moderate frequencies. An unprotected individual living in the Korhogo area received an average of 9.04, 0.63, 0.06 and 0.12 infected bites per night in September-October, November-December, February-March, and April-May, respectively. These results demonstrate that the intensity of malaria transmission is extremely high in the Korhogo area, especially during the rainy season. Malaria control in highly endemic areas such as Korhogo needs to be strengthened with complementary tools in order to reduce the burden of the disease.Une meilleure connaissance de la transmission du paludisme à l’échelle locale est essentielle pour élaborer et mettre en œuvre des stratégies de lutte efficaces. Dans le cadre d’un essai contrôlé randomisé, nous avons pour objectifs de fournir une description actualisée de la transmission du paludisme dans la zone de Korhogo, au nord de la Côte d’Ivoire, et de collecter les données de base pour l’essai. Nous avons capturé les moustiques sur des volontaires humains dans 26 villages de la zone de Korhogo pendant la saison pluvieuse (septembre–octobre 2016, avril–mai 2017) et la saison sèche (novembre–décembre 2016, février–mars 2017). À l’aide des techniques de PCR, nous avons déterminé les espèces au sein du complexe Anopheles gambiae, les infections par Plasmodium falciparum au stade sporozoïte et les mécanismes de résistance aux insecticides dans un sous-échantillon d’anophèles vecteurs. Anopheles gambiae s.l. est de loin le vecteur majoritaire du paludisme dans la zone de Korhogo. Au total, plus de vecteurs ont été collectés à l’extérieur des habitations qu’à l’intérieur (p < 0.001). Des 774 An. gambiae s.l. analysés au laboratoire, 89,65 % étaient An. gambiae s.s. et 10,35 % An. coluzzii. Les fréquences alléliques du gène kdr étaient très élevées chez An. gambiae s.s. alors que les fréquences alléliques du gène ace-1 étaient modérées. Une personne non protégée vivant à Korhogo reçoit chaque nuit en moyenne 9,04 piqûres infectantes (pi) en septembre–octobre, 0,63 pi en novembre–décembre, 0,06 pi en février-mars et 0,12 pi en avril–mai. Ces résultats démontrent que l’intensité de la transmission du paludisme est très élevée dans la zone de Korhogo, particulièrement en saison pluvieuse. La lutte contre le paludisme dans les zones de forte endémicité comme Korhogo doit être renforcée par des outils complémentaires afin de réduire le fardeau de la maladie

Anopheles bionomics, insecticide resistance and malaria transmission in southwest Burkina Faso: A pre-intervention study

International audienc