Introduction:

Bats are recognized as natural reservoirs of coronaviruses. Major human disease outbreaks caused by SARS-CoV, SARS-CoV-2, and MERS-CoV are presumed to have originated from zoonotic spillover of bat coronaviruses. Multiple bat species harbor SARS-CoV-like (Sarbecovirus) and MERS-CoV-like (Merbecovirus) viruses that use angiotensin-converting enzyme-2 (ACE2) or dipeptidyl peptidase-4 (DPP4) as a host cell receptor, similar to SARS-CoV, SARS-CoV-2, and MERS-CoV. This shared receptor tropism highlights the zoonotic and pandemic potential of bat coronaviruses and underscores the importance of evaluating the antiviral activity of inhibitors against them. Coronavirus 3CLpro cleaves the viral polyprotein into functional nonstructural proteins, essential for the viral replication cycle, and is conserved among coronaviruses, making it an attractive broad-spectrum antiviral target. This study aims to evaluate the antiviral activity of 3CLpro inhibitors against ACE2 or DPP4 utilizing bat coronaviruses.

Methodology:

Ten bat coronaviruses from the Betacoronavirus (Sarbecovirus and Merbecovirus) and Alphacoronavirus genera, along with SARS-CoV, SARS-CoV-2, MERS-CoV, and FIPV (Feline Infectious Peritonitis Virus), were included in this study. Their full-length 3CLpro genes were cloned and expressed. Nine 3CLpro inhibitors, including GC376, its analogs, and Nirmatrelvir, were tested against the expressed 3CLpros in the Fluorescence Resonance Energy Transfer (FRET) assay to determine 50% inhibitory concentrations (IC₅₀). X‑ray crystallography of bat coronavirus 3CLpro in complex with GC376 was performed. Additionally, we analyzed approximately 220 bat coronavirus 3CLpro sequences for amino acid homology and phylogeny.

Result:

Sequence analysis of these bat coronavirus 3CLpros revealed high homology within the Sarbecovirus (87-100%) and Merbecovirus (78-100%) subgenera and 41-100% homology within the Alphacoronavirus genus. Fifty percent or less homology was observed among the different coronavirus genera. In the FRET assay, some compounds demonstrated potent broad-spectrum inhibition across all tested coronaviruses, including those utilizing ACE2 or DPP4 receptors.

Conclusion:

These preliminary results highlight the potential of 3CLpro inhibitors as antiviral candidates against bat coronaviruses with zoonotic potential.

Background: Antimicrobial resistance (AMR) remains a pressing global health challenge, disproportionately affecting low- and middle-income countries (LMICs). This study investigates the spectrum and proportion of multidrug-resistant (MDR) bacteria isolated from clinical samples processed at the Microbiology lab of the Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon.

Methods: Microbiological laboratory results from 2017 to 2023 were retrospectively analysed to assess the non-susceptibility rates of the most common isolates from seven major types of clinical specimens (urine, blood, stool, wound swabs, urethral swabs, ear swabs, and throat swabs). Standard cultures and interpretation of results were done according to Clinical Laboratory Standards Institute (CLSI) guidelines.

Results: A total of 5,401 were clinically relevant bacterial isolates. The most frequently identified pathogens were Escherichia coli (273/1050; 26%), Staphylococcus aureus (192/1050; 18%), β-hemolytic Streptococci (160/1050; 15%), and Klebsiella pneumoniae (69/1050; 6.6%). Urine samples predominantly yielded E. coli and K. pneumoniae, while S. aureus was most common in wound and blood cultures. Overall, (242/1050; 23%) of isolates were classified as MDR, with E. coli accounting for 40%(96/1050;) of these cases. The proportion of ESBL producers among Enterobacterales was 10.5% (55/522). Resistance to third-generation cephalosporins was notably high, especially among K. pneumoniae (28/69; 41%) and E. coli (34/273; 13%). Methicillin-resistant S. aureus (MRSA) represented 12% (22/192) of S. aureus isolates. According to the WHO 2024 bacterial priority pathogen list, 58/1050 (5.5%) of isolates including carbapenem-resistant Acinetobacter baumannii(3) and ESBL-producing Enterobacterales(55).

Conclusion: This study highlighted the spectrum of bacteria leading causes of clinical infections, in Lambaréné, with urinary isolates dominated by E. coli and wound/blood cultures by S. aureus. Antimicrobial resistance is widespread, with nearly one‑quarter of isolates classified as multidrug resistant, including ESBL-producing Enterobacterales and MRSA. The presence of WHO “Critical Priority” pathogens highlights an urgent need for strengthened surveillance, antimicrobial stewardship, and infection‑control strategies to curb the growing threat of resistance.

Introduction/Background

Rabies is a fatal zoonotic disease of public health concern. The direct fluorescent antibody (DFA) test is internationally recognized as the gold standard for postmortem rabies diagnosis, with some variations in sampling recommendations depending on the reference standard used. The United States National Rabies Diagnostic protocol recommends sampling both the brainstem and cerebellum for testing. Our study aimed to assess whether brainstem tissue alone is sufficient for reliable DFA diagnosis by comparing brainstem and cerebellar results from routine case submissions.

Methods

We reviewed 437 DFA-positive rabies cases submitted between January 2013 and January 2026 from multiple species [skunks (323), cats (41), bovines (41), horses (10), dogs (9), foxes (7), raccoons (2), sheep (1), goat (1), donkey (1), and llama (1)]. Brainstem and cerebellar impression smears were fixed in cold acetone, stained with fluorescein isothiocyanate, and examined for apple-green fluorescence indicating rabies antigen. Antigen distribution was graded on a scale of 1 to 4 based on abundance. Tissue scores were statistically compared using paired student t-tests and Pearson correlation.

Results

Brainstem and cerebellum scores demonstrated a high correlation (r = 0.93; N = 437; t = 52.40; DF = 435; P = 4.98 × 10⁻¹⁹⁰). The paired (two-tailed) Student’s t-test showed a small but significant difference (P = 0.0005; t = 3.48; DF = 436; mean difference = 0.03; 95% CI: 0.01–0.05) between brainstem (3.87 ± 0.39) and cerebellum (3.84 ± 0.51) scores.

Conclusions

Brainstem and cerebellum scores show a strong positive correlation indicative of consistent antigen detection. Brainstem showed higher mean scores compared to cerebellum. These findings provide supporting evidence towards revising minimum tissue sampling standards to allow for independent brainstem testing when optimal tissue collection is not feasible. This will improve diagnostic efficiency and biosafety without compromising diagnostic accuracy or public health protection.

Introduction
The global spread of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli, particularly those harboring CTX-M enzymes, represents a major public health concern due to their association with multidrug resistance and limited therapeutic options. In Mexico, increasing reports of CTX-M–producing E. coli have been documented in both hospital and community settings. However, the epidemiological and molecular characteristics of these isolates remain fragmented across individual studies. This study aimed to review the available evidence on the prevalence and molecular features of CTX-M–producing E. coli in clinical isolates from Mexico.

Methods
A systematic review was conducted in PubMed and Scopus to identify studies reporting ESBL or CTX-M–producing E. coli in Mexico. Eligible studies included original research articles describing clinical human isolates. Studies focusing exclusively on animals, food, environmental sources, or non-E. coli organisms were excluded. Data extracted included study location, infection type, number of isolates, prevalence of CTX-M genes, and molecular characteristics such as sequence types or plasmid profiles.

Results
Nine studies met the inclusion criteria, encompassing clinical isolates obtained from hospitals and outpatient settings across several regions of Mexico. The majority of studies reported CTX-M enzymes as the predominant ESBL type among E. coli isolates. CTX-M-15, CTX-M-14, and CTX-M-27 were the most frequently identified variants. Several studies also reported the presence of high-risk clones such as sequence type ST131 and plasmids belonging to the IncF family, highlighting the role of mobile genetic elements in the dissemination of resistance. Uropathogenic E. coli was commonly associated with multidrug resistance phenotypes and multiple virulence determinants.

Conclusions
CTX-M–producing Escherichia coli are widely distributed among clinical isolates in Mexico and represent a significant contributor to antimicrobial resistance in both hospital and community infections. The predominance of CTX-M variants and the circulation of high-risk clones underscore the importance of molecular surveillance and antimicrobial stewardship programs to limit the spread of resistant strains.

Introduction: Chronic Pseudomonas aeruginosa infection remains a leading driver of morbidity in cystic fibrosis (CF) and is tightly linked to antimicrobial resistance (AMR). However, treatment failure often occurs even when routine susceptibility testing suggests activity. Emerging evidence indicates that CF airways can act as an evolutionary niche where P. aeruginosa diversifies into co-existing subpopulations with distinct resistance and tolerance profiles. This abstract proposes a framework describing how within-host diversity and heteroresistance contribute to persistent infection and recurrent antibiotic exposure.

Methods: We developed a conceptual framework by synthesizing established mechanisms in CF microbiology and AMR research and mapping them to clinical decision points. The model integrates (i) spatially structured biofilms and mucus-associated microenvironments, (ii) adaptive evolution under repeated antibiotic selection, and (iii) phenotypic heterogeneity (including heteroresistance and tolerant subpopulations) that may be under-detected by single-colony testing. We outline measurable indicators suitable for evaluation, including longitudinal culture patterns, multi-isolate susceptibility profiles, genomic diversity signals, and recurrence-related outcomes.

Results: The framework identifies three mechanisms that can sustain apparent “discordance” between lab susceptibility and clinical response: (1) coexistence of minority resistant subpopulations that expand during therapy, (2) biofilm-associated tolerance reducing effective antibiotic killing despite susceptibility in planktonic assays, and (3) rapid adaptive shifts during repeated treatment cycles. These processes may increase antibiotic burden, promote selection pressure, and accelerate progression to difficult-to-treat phenotypes in CF.

Conclusions: CF-associated P. aeruginosa AMR is not solely a single-strain resistance problem but a dynamic within-host ecosystem challenge. Incorporating within-host diversity into diagnostics and stewardship such as multi-isolate testing and longitudinal surveillanc may better align therapy with real-world AMR biology and reduce treatment failure.

Background: Antimicrobial resistance (AMR) is a critical public health threat in the Philippines, necessitating rapid diagnostic tools for effective stewardship. This study evaluates the concordance between multiplex PCR resistance gene detection and conventional phenotypic culture-based susceptibility testing.

Methods: A cross-sectional analytical study was conducted at San Lazaro Hospital (June 2023 – April 2025) involving 109 patients. Resistance markers identified via multiplex PCR (including NDM, IMP, VIM, KPC, and CTX-M) were compared against culture-based resistance profiles.

Results: Concordance between AMR gene detection and phenotypic resistance patterns was notably low at 31.57%. Despite this, PCR enabled the rapid identification of critical carbapenemase and ESBL genes. In the 90 days prior to admission, 3rd and 4th generation cephalosporins were the most frequently used antibiotics, a trend that continued during hospitalization (utilized in 69% of cases), alongside carbapenems (29.8%).

Conclusion: The identification of resistance genes like NDM and KPC through molecular methods is critical for AMR surveillance and antimicrobial stewardship. While multiplex PCR provides rapid genotypic data essential for surveillance, its limited concordance with phenotypic susceptibility indicates it should complement, not replace, conventional culture. PCR may detect resistance genes that are not phenotypically expressed, or vice-versa, necessitating careful clinical interpretation. These findings emphasize the need for integrated diagnostic approaches to optimize antimicrobial stewardship in resource-limited settings.

Background: Multidrug-Resistant Tuberculosis (MDR-TB) is a constraining challenge for tuberculosis (TB) control worldwide. The MENA region accounts for a large part of the global MDR-TB burden.
Aim: To estimate the prevalence of MDR-TB and associated factors in the MENA region.
Methods: We searched for studies published in English and French on the subject up to 31st January 2026 on Web of Science, PubMed, Scopus, and Cochrane, without time restriction. Original studies reporting data on the prevalence of MDR-TB (resistance to rifampicin and isoniazid simultaneously) in individuals living in the MENA region were selected. The random effects model was used to perform the meta-analysis, considering the heterogeneity among the included studies, and the I2 statistic was used to assess heterogeneity.
Results: A total of 1239 articles were identified, and 25 studies from 6 countries were included in this review. The prevalence of MDR-TB in the MENA region ranged from 0% (95% CI: 0 - 4.1%) to 17.1% (95% CI: 10.6 - 25.4%). The estimated pooled prevalence was 3.54% (95% CI: 2.18 - 5.72%) with a high heterogeneity, I2 = 95.6%; 95% CI: 94.4 - 96.5%. Previous TB treatment, HIV infection, smoking and the presence of comorbidities were the most reported associated factors.
Conclusion: This review underscores the persistence of MDR-TB in the MENA region, suggesting insufficiency in TB control. Multisectoral interventions integrating strong prevention measures, standardized treatment protocols and measures to enhance treatment adherence should be implemented.

Background:
The Global Programme to Eliminate Lymphatic Filariasis (GPELF) has made substantial progress, with 21 countries confirmed as having eliminated lymphatic filariasis (LF) as a public health problem and 14 under surveillance. However, sustaining elimination following mass drug administration (MDA) and during post-validation phases remains a major challenge. This review aimed to systematically identify and characterize challenges affecting the sustainability of LF elimination globally.

Methods:
A systematic review was conducted in accordance with the PRISMA guidelines. PubMed/MEDLINE, Europe PubMed Central, DOAJ, and Scopus were searched (July–October 2025) without time restrictions. Search terms combined LF-related keywords (e.g., lymphatic filariasis, Wuchereria bancrofti, Brugia malayi) with post-elimination concepts (e.g., post-MDA, surveillance, recrudescence) and challenges. Studies reporting challenges were included and categorized into biological, vector-related, socio-behavioural, and health system domains. Data were extracted and synthesized thematically.

Results:
Fourteen studies from eight countries met the inclusion criteria, spanning three WHO regions: African (57%), South-East Asia (36%), and Western Pacific (7%). Most studies evaluated post-intervention settings (79%). Biological challenges were most frequently reported (86%), including persistent microfilaremia and circulating filarial antigen (CFA) positivity following MDA cessation, suggesting ongoing transmission. Limited post-validation evidence indicated possible persistence, with CFA prevalence around 2.2% up to seven years after validation. Health system challenges (86%), particularly surveillance gaps and operational weaknesses, were also prominent. Socio-behavioural (50%) and vector-related (43%) factors further contributed to continued transmission risk.

Conclusion:
Sustained LF elimination is hindered by persistent infection reservoirs, surveillance gaps, and socio-behavioural barriers. Regional variation highlights the need for context-specific strategies. Strengthening surveillance and response systems is essential to prevent recrudescence and ensure long-term elimination.

Introduction: Leishmaniasis is a neglected tropical disease affecting millions worldwide, and Sri Lanka has reported increasing human cases annually. The interaction between sand fly vectors, their gut microbiota, and Leishmania parasites influences human disease transmission. Understanding vector gut bacterial communities in disease-endemic areas is therefore important for developing novel strategies to interrupt human infection cycles.

Methods: Sand flies were collected from Mihintale, a confirmed leishmaniasis-endemic region with active human cases, to investigate gut bacterial profiles relevant to human disease transmission. Light traps were placed in peridomestic environments (buffalo cattle sheds) adjacent to human dwellings between 18:00-06:00 hours. Following morphological identification, 50 male and 50 female Phlebotomus argentipes and Sergentomyia punjabensis were surface-sterilized and dissected. Pooled male and female gut samples were subjected to next-generation sequencing of the 16S rRNA gene (V1-V9 regions) to characterize bacterial communities.

Results: Analysis revealed 75 bacterial genera in males and 53 in females across both Phlebotomus argentipes and Sergentomyia punjabensis populations collected from this disease-endemic region. Across both species, Methylobacterium was the most abundant genus in males (27.01%) and females (28.04%). Thirty bacterial genera constituted a core microbiota shared between sexes. Wolbachia was detected exclusively in female sand flies.

Conclusions: This culture-independent profiling provides baseline data on the gut bacterial communities associated with sand fly vectors in a Sri Lankan endemic region. The abundance of Methylobacterium merits further investigation to determine its suitability as a candidate for paratransgenesis. The detection of Wolbachia exclusively in females requires cautious interpretation, as it may reflect acquisition during blood feeding from other hosts rather than a stable endosymbiotic association. Future studies should focus on confirming the origin and heritability of Wolbachia in Phlebotomus argentipes and evaluating the functional role of core microbiota in vector competence to inform the development of microbiome-based intervention strategies.

Abstract

Introduction

Lymphatic filariasis (LF), a devastating tropical disease caused by the parasitic filarial worms Wuchereria bancrofti, Brugia malayi, and Brugia timori, continues to pose a substantial public health challenge in endemic tropical and subtropical regions. After malaria, it is the second most prevalent vector-borne illness. A wide range of clinical manifestations are associated with LF. The clinical symptoms of LF are varied, ranging from asymptomatic or subclinical infections with circulating microfilariae to pronounced pathologies such as lymphedema, elephantiasis, and hydrocele. The diagnosis of asymptomatic LF infections can be challenging since microscopy, serological tests, and antigen detection tests may exhibit decreased sensitivity in certain instances.

Methods

Serum samples were collected from 84 microfilaremic individuals and 48 healthy volunteers residing in the endemic districts of Eastern Uttar Pradesh. The serum samples were processed, and the metabolites were extracted and identified via High-Resolution Accurate Mass Spectrometry (HRAMS)-based metabolomics. Metabolomic data analysis was conducted using the default parameters of "Compound Discoverer 3.3.3.20" software. A two-tailed Student's t-test was employed to assess feature differences between healthy and microfilaremic groups. The p-value was adjusted using the Benjamini–Hochberg correction for false discovery rate (FDR). A p-value of <0.05 was regarded as statistically significant. The "MetaboAnalyst 6.0" platform was utilized for pathway and network analyses.

Results

A total of 161 metabolites were uncovered, with 24 exhibiting significant upregulation and 137 exhibiting significant downregulation. Multivariate and univariate statistical analysis demonstrated significant metabolic differences distinguishing microfilaremic individuals from healthy controls. Additionally, pathway analysis of the metabolites showed changes in the metabolism of arachidonic acid and unsaturated fatty acid synthesis. Network analysis identified metabolites that had significant clinical implications.

Conclusions

The findings indicate an alteration in the host serum metabolome during the microfilaremic stage of lymphatic filariasis, which could function as possible biomarkers for early disease detection, surveillance, and therapeutic intervention.