Rotavirus alphagastroenteritidis strains (RVAs) are important causes of gastroenteritis in infants and young children. Human RVAs typically belong to one of two genogroups with distinct genotype constellations: (i) Gx-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1 (Wa-like, P[8]Wa strains) or (ii) Gx-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2 (DS-1-like, P[4]DS-1 strains). Historically, intergenogroup reassortants containing a mix of Wa-like and DS-1-like genotypes were rarely identified. However, since 2012, there has been a worldwide emergence of reassortants that exhibit Wa-like P[8] VP4 genes in a DS-1-like genetic backbone (i.e., G1/2/3/8/9-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2). Here, we sought to determine whether the gene alleles of these emergent P[8] VP4-containing DS-1-like (P[8]DS-1) reassortants are genetically distinct from each other and from typical pure genogroup strains. To do this, the published genome sequences of 70 representative P[8]DS-1 reassortants collected between 2012 and 2022 from 14 countries were compared to those of P[8]Wa or P[4]DS-1 controls using bioinformatic approaches. Phylogenetic trees were constructed for each gene, revealing 2–4 intra-genotypic alleles (types A-D) for VP1-VP4, VP6, and NSP1-NSP4. The results showed that, irrespective of their G-genotypes, locations, or years of isolation, the majority of P[8]DS-1 strains exhibited closely related type B alleles. The type B alleles were rare but present in control strains that circulated in 2002–2011, suggesting that they pre-existed the emergence of the P[8]DS-1 strains. Nucleotide and amino acid changes that were unique to the type B alleles and those that were fixed in the predominant P[8]DS-1 reassortants were identified. These results are important, as they identify genetic signatures of P[8]DS-1 strains that may have influenced their fitness/emergence over the past 14+ years.
This study describes the first detection of the serotype O, EAST AFRICA-2 (O/EA-2) topotype of foot-and-mouth disease virus (FMDV) in Ethiopia. Samples were collected from FMD outbreaks affecting cattle and small ruminants during 2024–2025. Molecular analyses assigned 41/49 sequences to the O/EA-2 topotype which has not been previously detected in the country. These sequences shared close genetic identity (99.5%) to those from Sudan and Kenya, highlighting the transboundary expansion of this lineage into the Horn of Africa. Virus neutralization testing demonstrated antigenic match of two representative field isolates to five commercially available FMD vaccines. The emergence of O/EA-2 alters Ethiopia's viral landscape, which was previously dominated by the O/EA-3 and O/EA-4 topotypes. These findings motivate further studies to monitor the spread of this topotype and encourage authorities to adopt well-matched high-potency vaccines to mitigate the clinical impacts of outbreaks due to this lineage.
The Enterobacteriaceae family, which includes prominent pathogens such as K. pneumoniae, E. coli, and S. enterica, poses a significant global health threat due to the rapid dissemination of multidrug resistance and virulence determinants. Central to this dissemination are conjugative plasmids, which act as vehicles for horizontal gene transfer. Among the myriad defense systems that interact with these mobile genetic elements, the type IV-A CRISPR-Cas system stands out due to its enigmatic nature and unique plasmid-centric biology. Unlike canonical CRISPR-Cas systems that are chromosomal and target bacteriophages, type IV-A systems are predominantly encoded on large, conjugative plasmids, particularly those bearing IncHI1B/IncFIB replicons. This review synthesizes current evidence on the biology of type IV-A systems within Enterobacteriaceae, elucidating their role as mediators of inter-plasmid competition, their paradoxical association with the spread of antibiotic resistance and virulence genes, and their emerging applications as programmable tools. We explore the mechanistic basis for their function as a natural CRISPR interference (CRISPRi) system, the epidemiological landscape of their distribution, and the dual role they play in both constraining and facilitating the dissemination of clinically relevant traits. Finally, we propose ambitious research avenues, including the development of “plasmid-destroying” probiotics, the use of type IV-A systems as epidemiological biosensors, and the exploration of hypotheses concerning their role in mediating bacterial “altruism” or serving as a “genetic memory” of the plasmid “secretoome.”
Leishmaniasis, a neglected tropical disease caused by protozoan parasites of the genus Leishmania, constitutes a spectrum of diseases ranging from asymptomatic cases to symptomatic visceral and integumentary (cutaneous and mucous membranes) leishmaniasis. Asymptomatic carriers are suspected to represent a major hidden reservoir in endemic regions, which constitutes a main challenge for the control and potential elimination of the disease. This review discusses current knowledge on the immune dynamics, diagnostic challenges and transcriptomic signatures associated with asymptomatic Leishmania infection and immune dynamics of symptomatic cases, concentrating on the visceral and cutaneous forms of the disease. Understanding the molecular and immune processes behind asymptomatic carriage is essential for the strategies to be taken at many levels: therapy, transmission, as well as control. We show further that transcriptomics, proteomics and other advanced approaches represent powerful tools to identify and compare differential gene expression, immune pathways, and metabolic changes in symptomatic and asymptomatic cases. ONE SENTENCE SUMMARY: Asymptomatic infections constitute a major underestimated hidden reservoir for Leishmania infections in endemic regions ("silent host"), a main challenge for the control and potential elimination of the disease.
Background Histidine-rich protein 2 (HRP2)-based rapid diagnostic tests are widely used for Plasmodium falciparum malaria, but parasites lacking pfhrp2 may escape detection. Evidence from Côte d'Ivoire remains limited, and conventional PCR non-amplification requires cautious interpretation because it may also reflect low parasite DNA concentration, assay sensitivity, or primer-binding-site variation. Methods We conducted an exploratory cross-sectional survey of 140 symptomatic patients with microscopy-confirmed P. falciparum mono-infection at three health facilities in southern Côte d'Ivoire: Anonkoua-Kouté (peri-urban), Port-Bouët (urban), and Ayamé (semi-rural). Two regions of each gene, the exon 1-exon 2 junction and exon 2, were assessed by conventional PCR. Amplification profiles were summarized by study site, and exploratory associations with parasite density, age, and multiplicity of infection were examined. Results pfhrp2 profiles differed significantly among sites (p < 0.001). Complete non-amplification of both targets occurred in 6.0% (Anonkoua-Kouté), 60.0% (Ayamé), and 40.0% (Port-Bouët). pfhrp3 profiles did not differ by site (p = 0.452), although exon 1-exon 2 non-amplification with retained exon 2 amplification (−/+) was common (74%). Eight infections (5.7%) showed concurrent non-amplification of both exon 2 targets; six of these (75%) had densities <5000 parasites/μL versus 28/132 (21%) without (p = 0.003). Multiplicity of infection was not significantly associated. Conclusions Substantial site-level variation in presumptive pfhrp2 deletion profiles was observed. The association between concurrent exon 2 non-amplification and low parasite density should be interpreted cautiously due to potential PCR failure from reduced template. Larger surveillance studies with paired RDT/microscopy, quantitative controls, and genomic analysis are needed before policy changes.
