Mouhamadou Abdoulaye Sonko

Salmonella is a major bacterial pathogen in low-income countries, where it circulates among humans, animals, and the environment. Children with sickle cell disease (SCD) are particularly vulnerable to severe Salmonella infections. This study aimed to characterize Salmonella isolates causing infections in Senegalese children with SCD. Using antimicrobial susceptibility testing, whole-genome sequencing, and bioinformatic analysis, we investigated antibiotic resistance, serovar diversity, and virulence factors on 23 isolates from SCD patients with diverse clinical infections. The isolates belonged to 12 serovars, with Enteritidis predominating (n = 7). Twenty-two isolates were fully susceptible to antibiotics, while one was multidrug-resistant. Eight isolates (Enteritidis and Typhimurium) carried a virulence plasmid harboring the spvRABCD gene cluster. Core Salmonella pathogenicity islands (SPIs-1 to -5, -11, and -13), as well as SPI-10 and SPI-23, were detected in all isolates, whereas other SPIs were variably present. These results show high serovar diversity and low antimicrobial resistance among Salmonella isolates in children with SCD in Dakar, Senegal. Our findings suggest that strains causing diarrhea in healthy individuals may also cause invasive disease in SCD patients, highlighting the need for dedicated surveillance in this vulnerable population.

Objectives: SCD is one of the most prevalent inherited hemoglobin disorders globally, affecting over 300 000 newborns annually, with the majority born in sub-Saharan Africa. Children with SCD are particularly vulnerable to severe bacterial infections, which are a major cause of morbidity and mortality. Among these, Salmonella species, especially non-typhoidal Salmonella, are frequently implicated and are notably associated with osteomyelitis, a serious bone infection. In this study, we performed whole genome sequencing and genomic analysis of 12 Salmonella isolates recovered from osteomyelitis cases in children with SCD in Dakar, Senegal. Methods: The isolates’ identity was confirmed using a MALDI-TOF biotyper and antimicrobial susceptibility testing carried out using the disc diffusion method. Whole-genome sequencing was conducted on an Illumina platform and bioinformatic analyses carried out using open-access and custom tools. Results: The isolates belonged to seven serovars, with Enteritidis and Typhimurium being the most frequent (three isolates each). Antibiotic susceptibility testing showed that 11 isolates were fully susceptible to all tested drugs, while one was an extensively drug-resistant strain previously linked to a nosocomial outbreak in a neonatal unit. Most of the isolates contained important Salmonella virulence factors including several Salmonella Pathogenicity Islands and plasmid-borne virulence genes. Conclusion: These findings highlight the clinical significance of Salmonella infections in children with SCD in low-income settings and underscore the urgent need for genomic surveillance and targeted public health interventions to protect this high-risk population.

Despite contributing to the large disease burden in West Africa, little is known about the genomic epidemiology of Streptococcus pneumoniae which cause meningitis among children under 5 years old in the region. We analysed whole-genome sequencing data from 185 S . pneumoniae isolates recovered from suspected paediatric meningitis cases as part of the World Health Organization (WHO) invasive bacterial diseases surveillance from 2010 to 2016. The phylogeny was reconstructed, accessory genome similarity was computed and antimicrobial-resistance patterns were inferred from the genome data and compared to phenotypic resistance from disc diffusion. We studied the changes in the distribution of serotypes pre- and post-pneumococcal conjugate vaccine (PCV) introduction in the Central and Western sub-regions separately. The overall distribution of non-vaccine, PCV7 (4, 6B, 9V, 14, 18C, 19F and 23F) and additional PCV13 serotypes (1, 3, 5, 6A, 19A and 7F) did not change significantly before and after PCV introduction in the Central region (Fisher's test P value 0.27) despite an increase in the proportion of non-vaccine serotypes to 40 % (n=6) in the post-PCV introduction period compared to 21.9 % (n=14). In the Western sub-region, PCV13 serotypes were more dominant among isolates from The Gambia following the introduction of PCV7, 81 % (n=17), compared to the pre-PCV period in neighbouring Senegal, 51 % (n=27). The phylogeny illustrated the diversity of strains associated with paediatric meningitis in West Africa and highlighted the existence of phylogeographical clustering, with isolates from the same sub-region clustering and sharing similar accessory genome content. Antibiotic-resistance genotypes known to confer resistance to penicillin, chloramphenicol, co-trimoxazole and tetracycline were detected across all sub-regions. However, there was no discernible trend linking the presence of resistance genotypes with the vaccine introduction period or whether the strain was a vaccine or non-vaccine serotype. Resistance genotypes appeared to be conserved within selected sub-clades of the phylogenetic tree, suggesting clonal inheritance. Our data underscore the need for continued surveillance on the emergence of non-vaccine serotypes as well as chloramphenicol and penicillin resistance, as these antibiotics are likely still being used for empirical treatment in low-resource settings. This article contains data hosted by Microreact.