Samweli Yohana Bahati

Undernutrition increases tuberculosis (TB) risk, but whether severe undernutrition during latent TB infection (LTBI) produces blood transcriptional changes that resemble active disease or identify future TB remains unclear. We reanalyzed whole-blood RNA sequencing from adults with LTBI in GSE152218, comparing severe undernutrition (BMI =18.5 kg/m2; n=11). Genes and Reactome pathways were evaluated. A seven-module summary was compared with active TB among severely undernourished adults and tested prospectively in GSE79362 and GC6-74/GSE94438 after pathway-representation assessment. No genes reached FDR <0.05 in the primary model; two did only in sensitivity analysis. In contrast, 241 Reactome pathways were significant and directionally concordant in both models (NES rho=0.954), including complement/Fc-receptor, B-cell, phospholipid/phagocytosis, neutrophil, vascular, autophagy, and cytokine-signaling pathways. Most changed opposite to the active-TB comparison (178/241; pathway rho=-0.390). The seven-module score was unrelated to baseline progression in GSE79362 (adjusted OR per SD=1.090; P=0.6922). In GC6, four modules met the prespecified representation criterion; their baseline score was inversely associated with progression (adjusted OR per SD=0.711; P=0.0218), but secondary and longitudinal analyses were non-confirmatory. Severe undernutrition during LTBI is associated with reproducible immune- and metabolism-related transcriptional remodeling that differs from active-TB biology and does not consistently identify future TB progression.

SUMMARY: Invasive non-typhoidal Salmonella (iNTS) disease is a severe bloodstream and focal invasive infection caused by non-typhoidal serovars of Salmonella enterica , especially S . Typhimurium and S . Enteritidis. Its clinical importance is disproportionate to its routine visibility because disease often presents as undifferentiated fever, sepsis, meningitis, severe anaemia-associated deterioration, recurrent bacteraemia, or focal infection, while definitive recognition depends on blood or other sterile-site microbiology. Global estimates indicate substantial mortality, but the true incidence remains uncertain because blood-culture access, prior antimicrobial exposure, specimen volume, and surveillance intensity vary widely. The vaccine-development era has intensified the need for a unified clinical microbiology framework. Prevention of invasive disease requires host-risk recognition, laboratory-confirmed endpoints, antimicrobial susceptibility testing, lineage-aware genomic surveillance, reservoir assessment, and post-introduction systems able to detect residual disease, breakthrough infection, non-target serovars, lineage shifts, and resistant invasive clones. This narrative review synthesizes the clinical, immunological, genomic, diagnostic, antimicrobial resistance, and vaccine era evidence relevant to iNTS control. Emphasis is placed on immune evasion, macrophage survival, T-cell dysfunction, immunosuppressed hosts, diagnostic blind spots, treatment under uncertainty, and the integration of laboratory systems with surveillance and prevention policy.

Brucella melitensis has a highly conserved genome, but the distribution of core-genome, gene-content, virulence-associated, mobile-element-associated, and antimicrobial-resistance-relevant variation among available sub-Saharan African genomes has not been examined in an integrated regional analysis. We analyzed 51 curated B. melitensis genomes from human and animal hosts using core-genome phylogenomics, pangenome reconstruction, virulence profiling, mobile genetic element (MGE) analysis, and mutation-based screening of antimicrobial resistance (AMR)-associated loci. A phylogeny reconstructed from 6,060 shared SNP sites resolved a dominant ST12-associated lineage, together with ST7, ST8, ST42, and novel sequence type branches. Individual genomes differed from the reference by 1,677–2,579 SNPs. The pangenome comprised 3,457 gene families, including 3,049 persistent families, indicating strong genome conservation, and limited accessory expansion. Virulence profiling identified 66 VFDB-associated genes; 48 genomes carried all 66, and the remaining three retained more than 98% of the virulence repertoire. Conserved determinants included the VirB type IV secretion system, lipopolysaccharide biosynthesis, intracellular survival pathways, and stress-response functions. MGE-associated variation was restricted to a small number of regions dominated by transposases and insertion-sequence-associated proteins. A GspF-domain-containing secretion-associated locus was detected only in BM2, although no complete type II secretion system gene cluster was identified. Recurrent substitutions occurred in AMR-relevant chromosomal loci, including rpoB , gyrA , gyrB , parC , parE , folA , folP , bepCDEFG, and mprF , but none corresponded to validated resistance-conferring alleles. The available regional genomes therefore comprise multiple phylogenetic lineages within a strongly conserved gene and intracellular virulence framework, with diversity concentrated in core-genome SNPs and localized genomic regions. IMPORTANCE: Brucella melitensis is a major zoonotic pathogen at the livestock-human interface, but genome-resolved evidence from sub-Saharan Africa remains limited. This study curates available regional genomes and shows that the population is dominated by a conserved intracellular virulence backbone, strong core-genome conservation, and focal genomic diversification rather than by extensive accessory-genome expansion. By integrating phylogenomics, pangenome analysis, virulence profiling, mobile-element characterization, and mutation screening of antimicrobial-resistance-associated loci, the work provides a regional framework for One Health genomic surveillance and identifies candidate loci requiring phenotype-linked validation.

Background and Aims: Tetanus‐toxoid‐containing vaccines protect mothers and newborns, but cumulative uptake may decline at higher dose thresholds. We assessed knowledge, attitudes, self‐reported tetanus‐toxoid‐containing vaccine uptake, and factors associated with receipt of at least three doses among women aged 15–44 years in Ifakara Town, Tanzania. Methods: A community‐based analytical cross‐sectional study included 383 women aged 15–44 years; electronic records were submitted between September 14, 2025, and January 6, 2026. Participants were selected through multistage sampling and completed an interviewer‐administered questionnaire. The primary outcome was self‐reported receipt of at least three tetanus‐toxoid‐containing vaccine doses. Participant‐level data were reanalyzed using multivariable logistic regression. The parity‐adjusted complete‐case model included 382 women; Firth bias‐reduced regression assessed sparse‐data sensitivity. Results: Almost all participants had heard of tetanus vaccination (97.7%) and reported ever receiving it (97.4%). Self‐reported uptake was 80.7% for at least two doses, 66.6% for at least three doses, 38.4% for at least four doses, and 24.5% for five doses. Good knowledge was reported for 66.1%, and 74.4% had a positive attitude score. In the parity‐adjusted model, the odds of reporting at least three doses were higher for ages 26–35 years (aOR 2.89, 95% CI 1.34–6.20) and 36–44 years (aOR 5.89, 95% CI 1.66–20.96), healthcare‐provider information (aOR 2.06, 95% CI 1.07–3.97), and parous status (aOR 15.94, 95% CI 6.84–37.14). Education, knowledge, and reported access barriers were not independently associated after parity adjustment. Conclusion: Initial contact with tetanus vaccination services was high, but self‐reported uptake declined at higher dose thresholds. Age and parity probably reflect cumulative opportunities for vaccination, rather than causal effects. Dose‐history review, provider‐led counseling, and access support may improve cumulative uptake.

Human antiviral restriction factors act across multiple stages of viral replication, but whether their population-resolved haplotype architecture differs systematically from comparable genomic regions is unclear. We tested this using phased public human genomic data from 660 individuals in seven African and African-diaspora populations, representing 30 canonical restriction-factor units and 436 target windows. Each canonical unit was compared with 80 exact matched genomic controls, yielding 2,400 frozen controls and 4,429,760 target-control endpoint comparisons across 19 retained haplotype endpoints. All 30 canonical units showed lower differentiation effects and lower robust population-private haplotype effects than their matched controls. Within-population diversity effects were higher in 19 of 30 units, whereas dominant-haplotype concentration effects were lower in 22 of 30. Nineteen units occupied a deconcentrated/high-diversity state, eight a concentrated/low-diversity state, and three a lower-diversity/lower-concentration state. Of 127 global endpoint/context summaries, 88 reached a global false-discovery-rate q value below 0.05; 76 were lower in restriction-factor targets and 12 were higher. Directional sign-test inference detected widespread repeated displacement relative to matched controls, whereas no matched-cell empirical-rank test reached global false-discovery-rate significance. These results show that human antiviral restriction-factor loci occupy a reproducible matched-control haplotype architecture characterized by attenuated population partitioning and reduced robust private structure, together with substantial locus-specific variation in within-population diversity and haplotype concentration. The comparative framework separates population-genomic structure from claims of functional or adaptive causality.

The Klebsiella oxytoca species complex (KoSC) comprises taxonomically diverse commensals and opportunistic pathogens, but its genomic diversity remains poorly characterized across Africa. We curated publicly available African KoSC data through raw-read and public-assembly routes and analyzed 163 African genomes together with 282 global comparators. Pangenome, phylogenomic, sequence-typing, surface-locus, antimicrobial-resistance, plasmid-replicon, mobile-element, biosynthetic-gene-cluster, and virulence-component analyses were integrated. The African collection comprised K. michiganensis (112/163), K. oxytoca (36/163), K. pasteurii (8/163), and K. grimontii (7/163) from 13 countries. The African pangenome contained 4,286 core, 4,505 shell, and 18,066 cloud gene families. Official PubMLST sequence types were assigned to 129/163 genomes. Four core/intrinsic antimicrobial-resistance-associated loci (ompA, oqxA, oqxB, and blaOXY) occurred in all genomes, whereas acquired resistance determinants were heterogeneous. Intact til biosynthetic gene clusters occurred in 55/163 genomes and intact leup clusters in 103/163. leup was concentrated in K. michiganensis (102/112), whereas intact til was frequent in K. oxytoca (26/36), K. pasteurii (7/8), and K. grimontii (7/7). Klebsiella-focused Virulence Factor Database screening detected at least one curated component in 112/163 genomes, but no complete curated factor; three K. michiganensis genomes carried complete mrkABCDF structural-operon candidates. These data define an African genome-resolved baseline for KoSC diversity and identify species-structured biosynthetic loci alongside heterogeneous resistance and mobilome profiles.

Campylobacter jejuni and Campylobacter coli occupy diverse animal reservoirs, yet the genomic processes associated with variation in host breadth remain poorly resolved in East Africa. Publicly available isolate-level whole-genome sequencing data from Ethiopia, Kenya, Tanzania and Uganda were analysed using a standardized population-genomic workflow. After genome reconstruction, species confirmation and quality filtering, 722 genomes were retained, comprising 586 C. jejuni and 136 C. coli . Animal-host breadth among sufficiently represented Ethiopian C. jejuni lineages was standardized by exact rarefaction across chicken, cattle, goat and sheep hosts. Fifteen lineages were eligible for discovery analyses. Host breadth showed no detectable association with homologous recombination, accessory-genome fluidity, human representation, antimicrobial-resistance class burden, recurrent AMR evolution or regional recurrence. Six discovery lineages recurred outside Ethiopia, but only one occurred in at least two validation countries, and validation animal sampling was insufficient for inferential replication of host-breadth or AMR associations. Recurrent within-lineage AMR evolution was restricted to a small number of determinants, lineage combinations involving tet(O) and gyrA T86I. Analysis of complete single-copy loci identified a restricted set of strongly supported cross-species placements, providing evidence consistent with localized interspecies introgression without implying whole-genome admixture or transfer direction. These findings indicate that animal-host breadth in regional C. jejuni populations is not explained by simple lineage-wide measures of genome exchange, human occurrence or AMR burden, but instead reflects lineage-specific combinations of ecological opportunity, selected genomic variation and population history. Significance: Campylobacter circulates among livestock, poultry and people, but it remains unclear why some lineages occur across several animal hosts whereas others are more restricted. Across East African populations, broader animal-host range was not consistently linked to greater genome-wide genetic exchange, human occurrence or antimicrobial resistance, although localized genetic exchange between C. jejuni and C. coli was detected. These findings show that host range is unlikely to be explained by a single genome-wide evolutionary process and instead highlight the importance of lineage-specific ecology and genetic change when interpreting transmission risk and designing genomic surveillance.

Campylobacter jejuni is a leading foodborne cause of gastroenteritis, but genomic surveillance remains uneven across Africa. A recent East Africa study combined whole-genome sequencing and antimicrobial susceptibility testing for Campylobacter isolates from humans with diarrhea in Kenya and poultry in Tanzania, showing high sequence-type diversity and substantially higher multidrug resistance in poultry. We extended this regional evidence by analyzing 1,013 publicly available C. jejuni genomes, including 718 African and 295 non-African comparator genomes, with standardized assembly, genotyping, phylogenomics, pangenome reconstruction, antimicrobial resistance, virulence, and mobile-element profiling. African genomes were geographically concentrated but genetically diverse, included globally distributed and regionally enriched lineages, and showed an open pangenome dominated by low-frequency gene families. Resistance and virulence determinants were unevenly distributed by region and lineage. These findings place African C. jejuni diversity within a global evolutionary framework and support expanded, integrated One Health genomic surveillance.