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Summary: Intrapartum azithromycin prophylaxis has shown the potential to reduce maternal infections but showed no effect on neonatal sepsis and mortality. Antibiotic exposure early in life may affect gut microbiota development, leading to undesired consequences. Therefore, we here assessed the impact of 2 g oral intrapartum azithromycin on gut microbiota development from birth to the age of 3 years, by 16S-rRNA gene profiling of rectal samples from 127 healthy Gambian infants selected from a double-blind randomized placebo-controlled clinical trial (PregnAnZI-2). Microbiota trajectories showed, over the first month of life, a slower community transition and increase of Enterobacteriaceae (p = 0.001) and Enterococcaceae (p = 0.064) and a decrease of Bifidobacterium (p

Abstract Background This detailed genomic study characterised multi-drug resistant-Gram negative bacilli (MDR-GNB) carriage in neonates

Background: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). Methods: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. Results: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal ‘sentinel’ surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. Conclusions: The consortium’s aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies. Funding: No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210]).

Summary: Background: COVID-19, caused by SARS-CoV-2, is one of the deadliest pandemics of the past 100 years. Genomic sequencing has an important role in monitoring of the evolution of the virus, including the detection of new viral variants. We aimed to describe the genomic epidemiology of SARS-CoV-2 infections in The Gambia. Methods: Nasopharyngeal or oropharyngeal swabs collected from people with suspected cases of COVID-19 and international travellers were tested for SARS-CoV-2 with standard RT-PCR methods. SARS-CoV-2-positive samples were sequenced according to standard library preparation and sequencing protocols. Bioinformatic analysis was done using ARTIC pipelines and Pangolin was used to assign lineages. To construct phylogenetic trees, sequences were first stratified into different COVID-19 waves (waves 1–4) and aligned. Clustering analysis was done and phylogenetic trees constructed. Findings: Between March, 2020, and January, 2022, 11 911 confirmed cases of COVID-19 were recorded in The Gambia, and 1638 SARS-CoV-2 genomes were sequenced. Cases were broadly distributed into four waves, with more cases during the waves that coincided with the rainy season (July–October). Each wave occurred after the introduction of new viral variants or lineages, or both, generally those already established in Europe or in other African countries. Local transmission was higher during the first and third waves (ie, those that corresponded with the rainy season), in which the B.1.416 lineage and delta (AY.34.1) were dominant, respectively. The second wave was driven by the alpha and eta variants and the B.1.1.420 lineage. The fourth wave was driven by the omicron variant and was predominantly associated with the BA.1.1 lineage. Interpretation: More cases of SARS-CoV-2 infection were recorded in The Gambia during peaks of the pandemic that coincided with the rainy season, in line with transmission patterns for other respiratory viruses. The introduction of new lineages or variants preceded epidemic waves, highlighting the importance of implementing well structured genomic surveillance at a national level to detect and monitor emerging and circulating variants. Funding: Medical Research Unit The Gambia at London School of Hygiene & Tropical Medicine, UK Research and Innovation, WHO.

Summary: Background: Sepsis is a leading cause of neonatal death. Intrapartum azithromycin reduces neonatal nasopharyngeal carriage of potentially pathogenic bacteria, a prerequisite for sepsis. Early antibiotic exposure has been associated with microbiota perturbations with varying effects. This study aims to understand the effect of intrapartum azithromycin intervention on the developing nasopharyngeal microbiota of the child. Methods: Using 16S rRNA gene sequencing, we analysed the microbiota of 343 nasopharyngeal samples collected from birth to 12 months from 109 healthy infants selected from a double-blind randomized placebo-controlled clinical trial conducted in the Gambia (PregnAnZI-1). In the trial, 829 women were given 2g oral azithromycin or placebo (1:1) during labour with the objective of reducing bacterial carriage in mother and child during the neonatal period. The post-hoc analysis presented here assessed the effect of the intervention on the child nasopharyngeal microbiota development. Findings: 55 children were from mothers given azithromycin and 54 from mothers given placebo. Comparing arms, we found an increase in alpha-diversity at day-6 (p = 0·018), and a significant effect on overall microbiota composition at days 6 and 28 (R2 = 4.4%, q = 0·007 and R2 = 2.3%, q = 0·018 respectively). At genus level, we found lower representation of Staphylococcus at day-6 (q = 0·0303) and higher representation of Moraxella at 12 months (q = 0·0443). Unsupervised clustering of samples by microbial community similarity showed different community dynamics between the intervention and placebo arms during the neonatal period. Interpretation: These results indicate that intrapartum azithromycin caused short-term alterations in the nasopharyngeal microbiota with modest overall effect at 12 months of age. Further exploration of the effects of these variations on microbiome function will give more insight on the potential risks and benefits, for the child, associated with this intervention. Funding: This work was jointly funded by the Medical Research Council (UK) (MC_EX_MR/J010391/1/MRC), Bill & Melinda Gates Foundation (OPP1196513), and MRCG@LSHTM Doctoral Training Program.

Background: After its initial detection in Wuhan, China, in December 2019, SARS-CoV-2 has spread rapidly, causing successive epidemic waves worldwide. This study aims to provide a genomic epidemiology of SARS-CoV-2 in Burkina Faso. Methods: Three hundred and seventy-seven SARS-CoV-2 genomes obtained from PCR-positive nasopharyngeal samples (PCR cycle threshold score < 35) collected between 5 May 2020, and 31 January 2022 were analyzed. Genomic sequences were assigned to phylogenetic clades using NextClade and to Pango lineages using pangolin. Phylogenetic and phylogeographic analyses were performed to determine the geographical sources and time of virus introduction in Burkina Faso. Results: The analyzed SARS-CoV-2 genomes can be assigned to 10 phylogenetic clades and 27 Pango lineages already described worldwide. Our analyses revealed the important role of cross-border human mobility in the successive SARS-CoV-2 introductions in Burkina Faso from neighboring countries. Conclusions: This study provides additional insights into the genomic epidemiology of SARS-CoV-2 in West Africa. It highlights the importance of land travel in the spread of the virus and the need to rapidly implement preventive policies. Regional cross-border collaborations and the adherence of the general population to government policies are key to prevent new epidemic waves.