Abdul Karim Sesay

Aim: This detailed genomic study aimed to characterise multi-drug resistant-gram negative bacilli (MDR-GNB) intestinal and skin carriage in small vulnerable newborns and their paired mothers at a low-resource African hospital. Methods: This cross-sectional cohort study was conducted at the only neonatal referral unit in The Gambia with genomic analysis at MRC Unit The Gambia at LSHTM. Neonates K. pneumoniae and E. coli , with heterogeneous strain diversity, no evidence of clonality and 111 distinct antibiotic resistance genes, mostly Beta-Lactams ( Bla -AMPH, Bla- PBP, CTX-M-15, Bla- TEM-105). 76% (16/21) and 62% (13/21) of mothers had recto-vaginal carriage of at least 1 MDR-GNB and ESBL-GNB respectively, most commonly MDR- E. coli ( 76%, 16/21) and MDR- K. pneumoniae (24%, 5/21). Of 21 neonate-mother dyads only one had genetically identical isolates ( E. coli ST131 and K. pneumoniae ST3476). Conclusion: Gambian hospitalised small vulnerable neonates exhibit high MDR and ESBL-GNB carriage prevalence with acquisition between birth and 7 days. The heterogeneous strain diversity and lack of matching isolates between mothers and newborns suggests multiple environmental sources may be important in transmission. Larger genomic studies to confirm these findings in similar resource limited settings is foundational to inform targeted surveillance and infection prevention control policies. What is known: - MDR-GNB, especially Klebsiella pneumoniae and Escherichia coli , are important causes of neonatal invasive infections and mortality in Africa, classified by WHO as pathogens of high priority for research - Neonatal MDR-GNB carriage is a pre-curser for invasive infection, with preterm, low-birth weight neonates (“Small Vulnerable Newborns”) at greatest risk - Maternal MDR-GNB carriage is a risk factor for neonatal pathogen acquisition in Europe and other well-resourced settings, but a priority evidence gap exists for transmission pathways for small vulnerable African newborns What this study adds: - Hospitalised Gambian small vulnerable neonates have high carriage prevalence of MDR- and ESBL-GNB with acquisition occurring between birth and 7 days - Heterogeneous diversity of K. pneumoniae and E. coli strains suggests multiple environmental sources with no evidence of clonal outbreak - Beta-lactamase genes were most commonly identified with high rates of ESBL- and AMP-C gene production - Despite high maternal MDR-GNB carriage prevalence there is no genomic evidence indicating widespread transmission from mother to newborn

The COVID-19 pandemic continues to expand globally, with case numbers rising in many areas of the world, including the Eastern Mediterranean Region. Lebanon experienced its largest wave of COVID-19 infections from January to April 2021. Limited genomic surveillance was undertaken, with just 26 SARS-CoV-2 genomes available for this period, nine of which were from travellers from Lebanon detected by other countries. Additional genome sequencing is thus needed to allow surveillance of variants in circulation. In total, 905 SARS-CoV-2 genomes were sequenced using the ARTIC protocol. The genomes were derived from SARS-CoV-2-positive samples, selected retrospectively from the sentinel COVID-19 surveillance network, to capture diversity of location, sampling time, sex, nationality and age. Although 16 PANGO lineages were circulating in Lebanon in January 2021, by February there were just four, with the Alpha variant accounting for 97 % of samples. In the following 2 months, all samples contained the Alpha variant. However, this had changed dramatically by June and July 2021, when all samples belonged to the Delta variant. This study documents a ten-fold increase in the number of SARS-CoV-2 genomes available from Lebanon. The Alpha variant, first detected in the UK, rapidly swept through Lebanon, causing the country's largest wave to date, which peaked in January 2021. The Alpha variant was introduced to Lebanon multiple times despite travel restrictions, but the source of these introductions remains uncertain. The Delta variant was detected in Gambia in travellers from Lebanon in mid-May, suggesting community transmission in Lebanon several weeks before this variant was detected in the country. Prospective sequencing in June/July 2021 showed that the Delta variant had completely replaced the Alpha variant in under 6 weeks.

Invasive non-typhoidal Salmonella (iNTS) disease continues to be a significant public health problem in sub-Saharan Africa. Common clinical misdiagnosis, antimicrobial resistance, high case fatality and lack of a vaccine make iNTS a priority for global health research. Using whole genome sequence analysis of 164 invasive Salmonella isolates obtained through population-based surveillance between 2008 and 2016, we conducted genomic analysis of the serovars causing invasive Salmonella diseases in rural Gambia. The incidence of iNTS varied over time. The proportion of atypical serovars causing disease increased over time from 40 to 65 % compared to the typical serovars Enteritidis and Typhimurium that decreased from 30 to 12 %. Overall iNTS case fatality was 10%, but case fatality associated with atypical iNTS alone was 10 %. Genetic virulence factors were identified in 14/70 (20 %) typical serovars and 45/68 (66 %) of the atypical serovars and were associated with: invasion, proliferation and/or translocation (Clade A); and host colonization and immune modulation (Clade G). Among Enteritidis isolates, 33/40 were resistant to four or more of the antimicrobials tested, except ciprofloxacin, to which all isolates were susceptible. Resistance was low in Typhimurium isolates, but all 16 isolates were resistant to gentamicin. The increase in incidence and proportion of iNTS disease caused by atypical serovars is concerning. The increased proportion of atypical serovars and the high associated case fatality may be related to acquisition of specific genetic virulence factors. These factors may provide a selective advantage to the atypical serovars. Investigations should be conducted elsewhere in Africa to identify potential changes in the distribution of iNTS serovars and the extent of these virulence elements.

Simple group testing designs to improve SARS-CoV-2 surveillance in resource-constrained settings are identified using modeling and experimental data.