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Kariuki, S.

Publications and source records attributed to Kariuki, S..

6 recordsLinked to original sources

One Health assessment of antimicrobial-resistant Enterobacterales and ESKAPE pathogens in little stints (Calidris minuta) and aquatic ecosystems of the Kenyan Rift Valley

Palearctic migratory little stints (Calidris minuta) can acquire resistant bacteria from anthropized environments and spread them across different hosts and borders. This two-year cross-sectional study assessed the prevalence of multidrug-resistant (MDR) and extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales and ESKAPE pathogens isolated from C. minuta and their aquatic foraging ecosystems at two Kenyan Rift Valley lakes, Bogoria (low anthropogenic activities) and Magadi (high impact). A total of 184 fecal samples from C. minuta and 48 water samples were collected during the birds arrivals (cohort 1) and departures (cohort 2). Samples were cultured, bacterial isolates were identified using MALDI-TOF MS platform and tested against 12 antimicrobials using the Kirby-Bauer disk method. Of the 294 isolates (16 genera and 33 species), Enterobacter species (31%) and Escherichia coli (17.3%) were predominant. Resistance was highest for ampicillin (50%), amoxicillin-clavulanic acid (36.4%), and tetracycline (32.7%), and lowest for meropenem (1.0%) and cefepime (3.4%). The predominant MDR phenotype was a combination of resistances to ampicillin, tetracycline, and trimethoprim-sulfamethoxazole. Enterobacter species showed the highest frequencies of MDR (8.5%) and ESBL-MDR (4.4%) phenotypes, while Acinetobacter species were the most frequent ESBL producers. Despite observing higher median resistances in isolates from Lake Magadi (7.1), C. minuta (8.0) and cohort 2 (7.1) than those from Lake Bogoria (6.7), water samples (5.9) and cohort 1 (6.5), these differences were statistically insignificant (p-values= 0.833, 0.147, 0.210). This suggests that while human activities drive AMR spread, resistant strains are pervasive even in minimal human-influenced environments. This is the first study to link C. minuta to the AMR epidemiological circuit. Our findings underscore the need to include migratory wild birds in AMR surveillance in the Kenyan Rift Valley, to implement stringent environmental stewardship measures to curb anthroponotic AMR transmissions and utilizing whole-genome sequencing to accurately trace the origin and dissemination pathways of AMR strains.

microbiology↗

Continental-scale genomic surveillance of Plasmodium falciparum malaria with rapid nanopore sequencing

In sub-Saharan Africa, continental-scale genomic surveillance of Plasmodium falciparum malaria is needed to track the spread of antimalarial drug resistance and diagnostic test evasion, as well as to monitor parasite evolutionary responses to vaccine rollout. Yet implementation of malaria genomic surveillance at a continental-scale is hindered by resource constraints, the vastness of the continent, and the lack of sequencing protocols suitable for most local laboratories. To address this, we developed an approach to enable a decentralized scale-up of P. falciparum genomic surveillance and established it in six African countries in one year, locally sequencing 1,065 samples. The approach includes a rapid ([~] 5 hours) and cost-efficient (<$25 USD/sample) nanopore sequencing protocol that provides surveillance of drug resistance-associated genes, hrp2/3 deletions, the vaccine target csp, and the polymorphic gene ama1. We coupled this to a bioinformatics dashboard that runs offline on a laptop and displays mapping and variant calling results in real-time. We demonstrate robust sequencing coverage across parasitemia levels and laboratories, accurate identification of antimalarial resistance markers and hrp2/3 deletions; and, with a novel variant caller, sensitive detection of mutations carried by minor clones. Our approach will accelerate genomic surveillance of P. falciparum malaria across sub-Saharan Africa at a time of urgent need.

genomics↗

Aeromonas: Genomic Insights into an Environmental Pathogen and Reservoir of Antimicrobial Resistance

Aeromonads are an ecologically versatile group of bacteria that cause infection in aquatic animals and are recognised as an emerging human pathogen. Despite this, our understanding of Aeromonas diversity, especially the relationship between clinical and environmental strains, remains limited. Here, we present a complete view of the Aeromonas genus, comprising 1,853 genomes, and a detailed comparison of clinical and environmental strains from South Asia, including 996 newly sequenced genomes from Bangladesh and India. Phylogenetic analyses revealed that Aeromonas is a highly diverse genus, with no distinct clade separating clinical and environmental isolates. We identified 28 Aeromonas species and 905 novel sequence types, comprising 72.5% of the genomes. Notably, we show a high incidence of AMR genes across all isolates, including against front and last-line antibiotics. Finally, we highlight frequent misidentification of Aeromonas as Vibrio cholerae, key to cholera-endemic regions where both genera co-exist and are associated with diarrhoeal disease. Our study underscores Aeromonas as an important environmental AMR reservoir and emerging multi-species pathogen capable of spilling over into human populations.

genomics↗

Rare twin cysteine residues in the HIV-1 envelope variable region 1 link to neutralization escape and breadth development

The identification of HIV-1 Envelope glycoprotein (Env) traits associated with development of neutralization cross-reactivity in natural infection is critical for vaccine design. Here we describe the presence of additional Cysteine (Cys) residues in V1 that are enriched among people with elite neutralization breadth. Using >65,000 V1 sequences from the CATNAP database, the AMP trials and three large longitudinal HIV infection cohorts, the SHCS, ZPHI and CAPRISA studies, we show that Env variants with extra V1 Cys are present at low levels throughout infection and fluctuate in frequency over time within participants. We demonstrate an independent association of extra V1 Cys with elite plasma neutralization, and a strong preference for two versus one extra Cys, suggesting certain Envs introduce an additional disulfide bond for stabilization. We observed high levels of neutralization resistance among Envs from 34 bNAb donors, of which 17.6% had elongated V1 regions with extra Cys. We show that extra V1 Cys moderately increase neutralization resistance in an Env from a V2- Apex bNAb-inducer. Modulation of the accessibility of bNAb epitopes on this Env by extra V1 Cys enhanced epitope shielding of several regions, but increased V2 exposure. This suggests that escape from autologous neutralizing activity drove insertion of the extra V1 Cys, creating a modified antigen that may have favored V2 bNAb induction in this donor. Overall, we identify a rare motif of twin Cys in V1 that confers increased neutralization resistance and Env stabilization, is associated with bNAb induction, and may hold potential for incorporation into future HIV bNAb immunogens.

immunology↗

Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya

Understanding the dynamics of infection and carriage of typhoid in endemic settings is critical to finding solutions to prevention and control. In a 3 year case-control study, we investigated typhoid among children aged <16 years (4,670 febrile cases and 8,549 age matched controls) living in an informal settlement, Nairobi, Kenya. 148 S. Typhi isolates from cases and 95 from controls (stool culture) were identified; a carriage frequency of 1%. Whole-genome sequencing showed 97% of cases and 88% of controls were genotype 4.3.1 (Haplotype58), with the majority of each (76% and 88%) being multidrug-resistant strains in 3 sublineages of H58 genotype (East Africa 1 (EA1), EA2, and EA3), with sequences from cases and carriers intermingled. The high rate of multidrug-resistant H58 S. Typhi, and the close phylogenetic relationships between carriers and controls, provides evidence for the role of carriers as a reservoir for the community spread of typhoid in this setting.

physiology↗

Genomic diversity and antimicrobial resistance among non-typhoidal Salmonella associated with human disease in The Gambia

Non-typhoidal Salmonella associated with multidrug resistance cause invasive disease in sub-Saharan African. Specific lineages of serovars S. Typhimurium and S. Enteritidis are implicated. We characterised the genomic diversity of 100 clinical Non-typhoidal Salmonella collected from 93 patients in 2001 from the eastern and 2006 to 2018 in the western regions of The Gambia respectively. Phenotypic susceptibility applied Kirby Baur disk diffusion and whole genome sequencing utilized Illumina platforms. The predominant serovars were S. Typhimurium ST19 (31/100) and S. Enteritidis ST11 (18/100) restricted to invasive disease with the notable absence of S. Typhimurium ST313. Phylogenetic analysis performed in the context of 495 African strains from the European Nucleotide Archive confirmed the presence of the S. Enteritidis virulent epidemic invasive multidrug resistant West African clade. Multidrug resistance including chloramphenicol and azithromycin has emerged among the West African S. Enteritidis clade 7/9 (78%) with potential for spread, thus having important implications for patient management warranting systematic surveillance and epidemiologic investigations to inform control. Data summarySequences are deposited in the NCBI sequence reads archive (SRA) under BioProject ID:PRJEB38968. The genomic assemblies are available for download from the European Nucleotide Archive (ENA): http://www.ebi.ac.uk/ena/data/view/. Accession numbers SAMEA6991082 to SAME6991180

genomics↗