Search Results (115)

Background: The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Salmonella enterica serovar Typhi has severely constrained typhoid treatment. Pakistan is a major hotspot for XDR typhoid, yet genomic evidence defining the molecular basis of antimicrobial resistance, virulence, and genomic diversity of circulating strains remains limited. Methods: A cross-sectional study was conducted from January to December 2021 involving 252 culture-confirmed S. Typhi isolates collected from patients with suspected typhoid fever in Peshawar, Pakistan. Isolates were identified by conventional microbiological methods, biochemical testing, and 16S rRNA PCR. Antimicrobial susceptibility testing (AST) was performed according to CLSI guidelines, and isolates were classified as susceptible, MDR, or XDR following WHO criteria. Fourteen non-duplicate XDR isolates were selected for Illumina whole-genome sequencing (WGS). Bioinformatic analyses included genome assembly, multilocus sequence typing (MLST), resistome and virulome characterization, mutation analysis, pan-genome analysis, and core-genome phylogenetic reconstruction. Pearson’s chi-square goodness-of-fit test was used to assess categorical distributions, with p < 0.05 considered statistically significant. Results: Among the 252 isolates, 152 (60.3%) were XDR, 73 (29.0%) were MDR, and 27 (10.7%) were susceptible. The distributions of sex, age group, and phenotypic classification differed significantly from equal expected proportions (p = 0.001, p = 0.013, and p < 0.001, respectively). Resistance was highest to ciprofloxacin, ampicillin, chloramphenicol, ceftriaxone, and co-Trimoxazole, whereas azithromycin and meropenem showed high in vitro activity. WGS showed that all sequenced isolates belonged to sequence type ST1 and had conserved genome sizes (4.84–4.95 Mb) with ~54% GC content. The resistome included blaCTX-M-15, blaTEM-1, catA1, sul1, qnrS1, aac(6′)-Iy, and dfrA7, with mutations in gyrA, parC, soxS, pmrA, and pmrB. Virulence genes associated with adhesion, type III secretion, Vi capsule biosynthesis, intracellular survival, iron acquisition, and typhoid toxin were conserved across all isolates. Pan-genome analysis indicated limited pan-genome expansion within the sequenced collection, while phylogenomic analysis showed high genetic relatedness among the sequenced isolates, indicating substantial genomic conservation within this collection. Conclusions: The high genomic relatedness and limited gene-content variation observed within the 14 sequenced XDR isolates support a genetically conserved collection, but do not by themselves establish ongoing transmission or clonal expansion. Larger and more geographically diverse genomic datasets are needed to determine the broader population structure of XDR S. Typhi in Pakistan. Continued genomic surveillance, appropriate antibiotic use, typhoid conjugate vaccination, and effective infection-control measures are needed to reduce transmission of drug-resistant typhoid. Full article

Typhoid fever, caused by Salmonella enterica serovars Typhi and Paratyphi, remains a major public health threat across Africa and Asia and causes substantial annual morbidity. Transmission persists in low- and middle-income countries (LMICs), where access to safe water and sanitation is limited. While improvements in water, sanitation, and hygiene (WASH) are essential, slow implementation makes vaccination the most practical preventive strategy. Current licensed vaccines have limitations, including suboptimal immune coverage in infants, limited duration of protection, and cold-chain requirements. This review examines bacteriophage-based vaccine platforms as emerging preclinical strategies for typhoid prevention. Phage technologies, including phage display, phage DNA, and hybrid models, offer potential advantages such as multivalent antigen display, projected thermostability, and cost-efficient production using bacterial manufacturing systems. Based on animal immunogenicity and proof-of-concept studies, these systems could theoretically induce durable immunity and broaden age-group protection, although their clinical feasibility and scalability remain unproven. We evaluate key technical hurdles, including endotoxin contamination, host-strain engineering, and payload-expression constraints. We also discuss how these potentially low-cost platforms may contribute to global antimicrobial resistance (AMR) mitigation efforts. Although phage-based vaccines remain in the preclinical stage, they represent promising research platforms for advancing vaccine equity and infectious disease resilience, provided regulatory and technical challenges are overcome. However, significant translational gaps must still be bridged before clinical application can be realized. Full article

Malaria and typhoid fever co-infection produces severe illness affecting public health, especially in countries where both diseases coexist. A mathematical model that considers the critical factors influencing the transmission dynamics and control interventions of malaria and typhoid fever co-infection is developed. The essential epidemiological features of the model, such as the basic reproduction number and disease-free equilibrium, are determined and analysed. A dynamical systems analysis of the model reveals the conditions under which the disease can be eradicated or persists. Numerical simulations are conducted using real data from Nigeria as a case study. By fitting the model to the real data, essential parameter values are estimated and model prediction that reveals the possible long-term dynamics of the model is determined. The impact of the various control interventions are investigated. These findings are anticipated to aid in improving the management of malaria–typhoid co-infection in endemic regions for expeditious disease eradication. Full article

Background: International travel has increased over recent decades, leading to a rise in the number of patients presenting to emergency departments (EDs) with fever after returning from abroad. Evaluating fever in returning travelers is challenging because the differential diagnosis is broad, and exposure to tropical diseases limited, among most ED clinicians. Objective: This article aims to provide a practical overview of the most common travel-related causes of fever. The tool is intended to support targeted diagnostics and timely treatment and/or timely specialist referral, while emphasizing that non-travel-related infections must also be considered. Methods: We created a clinical summary of the most common causes of fever in returning travelers based on epidemiology, incubation periods, clinical features, and diagnostic approaches. A practical overview was created to aid ED clinicians in evaluating stable patients, incorporating travel history, exposure risks, and key clinical findings. Results: Malaria, dengue and typhoid fever are among the most common diagnoses in travelers returning from abroad, excluding non-travel-related diseases. These conditions share overlapping symptoms. Diagnosis relies on clinician awareness and a combination of exposure history, clinical evaluation, and targeted laboratory testing. Treatment depends on the causative pathogen and disease severity, but often requires early empiric therapy and supportive care. Conclusions: This article presents a systematic, pragmatic approach to the evaluation of fever in the returning traveler. This overview is designed to help ED clinicians recognize and make appropriate initial management and referral decisions when assessing a stable traveler. Nevertheless, we recommend specialist advice for most cases. Full article

The diagnosis of enteric fever has become difficult due to the nonspecific and overlapping clinical syndrome of typhoid and paratyphoid infections with other febrile illnesses. Moreover, the rapid emergence of fluoroquinolone-resistant typhoidal Salmonella and the lack of robust diagnostic methods highlight the urgent need for highly sensitive molecular techniques. Here, we evaluated the performance of a rapid, reliable, and cost-effective molecular diagnostic approach for detecting Salmonella Typhi, including the globally dominant haplotype H58 lineage (H58), and Salmonella Paratyphi A. An in-house-built conventional polymerase chain reaction (PCR) was performed on a collection of blood-culture-positive strains, and the sensitivity and specificity were compared with those of the standard blood culture results. H58 and non-H58 Typhi lineages with distinct resistance patterns were confirmed from the previously reported sequencing data. Our PCR result showed that target genes SSPA2308, STY2513, and STY0307 demonstrated 100% sensitivity and specificity for Salmonella Paratyphi A, Salmonella Typhi, and H58 Salmonella Typhi, respectively. The PCR assay reliably detected bacterial DNA at 5.2 × 10⁴ colony-forming units (CFUs), with consistent amplification observed up to 10⁻¹ dilution. This single-nucleotide polymorphism (SNP)-based diagnostic approach has added a new dimension to designing unique markers for multidrug-resistant (MDR)-associated H58 lineage detection and has the potential to inform local treatment algorithms. Full article

Background/Objectives: Typhoid fever remains a major public health challenge in many low-income countries, where overlapping clinical symptoms and the limited reliability of conventional diagnostic procedures hinder accurate diagnosis. This study aims to develop a reliable and efficient diagnostic framework that automates typhoid fever detection from clinical data while preserving patient privacy. Methods: To achieve this objective, we propose a hybrid framework combining genetic algorithm (GA)–based feature selection, a Convolutional Neural Network–Long Short-Term Memory (CNN–LSTM) deep learning classifier, and federated learning. The GA identifies the most informative clinical features, reducing redundancy and computational complexity. The selected features are then used to train a CNN–LSTM model in a federated learning setup using the Federated Averaging (FedAvg) algorithm, enabling collaborative model training across multiple clients without sharing raw patient data. Results: Experimental results show that the proposed framework achieves 92% accuracy, with a strong F1-score and satisfactory sensitivity. Compared to models trained on the full feature set, the proposed approach requires less memory and shorter training time, while maintaining balanced performance under class imbalance. Conclusions: These results demonstrate that integrating evolutionary feature selection, deep sequential learning, and federated training provides an effective and privacy-aware solution for multi-class typhoid fever diagnosis. The proposed framework is particularly suitable for clinical environments with limited data access and constrained resources. Full article

This paper presents a unified analytical and computational framework for the study of typhoid fever transmission dynamics governed by a Caputo fractional-order compartmental model of order $\kappa \in (0,1]$. The population is stratified into five epidemiological classes, namely susceptible $\left(\mathcal{S}\right)$, asymptomatic $\left(\mathcal{A}\right)$, symptomatic $\left(\mathcal{I}\right)$, hospitalised $\left(\mathcal{H}\right)$, and recovered $\left(\mathcal{R}\right)$, and the governing system explicitly incorporates asymptomatic transmission, treatment dynamics, and temporary immunity with waning. The use of the Caputo fractional derivative is motivated by the well-documented existence of chronic asymptomatic Salmonella Typhi carriers, whose heavy-tailed sojourn times in the carrier state are naturally encoded by the Mittag–Leffler waiting-time distribution arising from the fractional operator. A complete qualitative analysis of the fractional system is carried out: the basic reproduction number ${\mathcal{R}}_0$ is derived via the next-generation matrix method; local and global asymptotic stability of both the disease-free equilibrium ${\mathcal{E}}_0$ (when ${\mathcal{R}}_0\le 1$) and the endemic equilibrium ${\mathcal{E}}^{*}$ (when ${\mathcal{R}}_0>1$) are established using fractional Lyapunov theory and the LaSalle invariance principle; and the normalised sensitivity indices of ${\mathcal{R}}_0$ are computed to identify transmission-amplifying and transmission-suppressing parameters. Existence, uniqueness, and Ulam–Hyers stability of solutions are established via Banach and Leray–Schauder fixed-point arguments. To complement the analytical results, a fractional physics-informed neural network ($\mathcal{PINN}$) framework is developed to simultaneously reconstruct compartmental trajectories and identify unknown biological parameters from sparse synthetic observations. $\mathcal{PINN}$ embeds the L1-Caputo discretisation directly into the training residuals and employs a four-stage Adam–L-BFGS optimisation strategy to recover five trainable parameters $\mathbf{\Theta }$ = $\{\varphi ,\mu ,\sigma ,\psi ,\beta \}$ across three fractional orders $\kappa \in \{1.0,0.95,0.9\}$. The estimated parameters show strong agreement with the true values at the classical limit $\kappa =1.0$ ($\mathrm{MAPE}=2.27\%$), with the natural mortality rate $\mu$ recovered with $\mathrm{APE}\le 0.51\%$ and the transmission rate $\beta$ with $\mathrm{APE}\le 3.63\%$ across all fractional orders, confirming the structural identifiability of the model. Pairwise correlation analysis of the learned parameters establishes the absence of equifinality, validating that $\beta$ can be reliably included in the trainable set. Noise robustness experiments under Gaussian perturbations of $1\%$, $3\%$, and $5\%$ demonstrate graceful degradation ($\mathrm{MAPE}$: $0.82\%\to 3.10\%\to 7.31\%$), confirming the reliability of the proposed framework under realistic observational conditions. Full article

Background/Objectives: Febrile illness in returning travelers presents a diagnostic and operational challenge for emergency medicine clinicians as early symptoms of high-consequence tropical infections often overlap with common viral syndromes. This review synthesizes current evidence to guide frontline clinicians in the systematic evaluation, diagnosis, and management of internally acquired febrile illnesses with a focus on pathogen of greatest relevance to United States (US) emergency departments (ED). Methods: We conducted a narrative review of the literature addressing epidemiology, clinical presentation, diagnostic testing, and management strategies for key travel-associated infections. Special consideration was given to rapid diagnostic modalities, pediatric risk factors, and infections most frequently implicated in returning travelers, including chikungunya (CHIK), dengue virus (DENV) disease, Ebola virus (EBV) disease, malaria, Mpox, typhoid fever (TF), yellow fever (YF), and Zika virus (ZIKV) disease. Results: Effective evaluation begins with a detailed travel and exposure history, recognition of epidemiologic and clinical red flags, and targeted use of rapid diagnostic tests. Malaria remains the most common life-threatening cause of post-travel fever and the only pathogen with reliable Food and Drug Administration (FDA)-cleared rapid testing available in the ED. Arboviral infections such as DENV, CHIK, ZIKV, and YFrequire region-specific consideration and phase-appropriate molecular or serologic evaluation. Emerging and high-consequence pathogens, including Mpox and EBV, necessitate strict infection control measures and coordination with public health authorities. Pediatric travelers, particularly those visiting friends and relatives, face disproportionate risk for severe systemic infections and often require broader diagnostic testing. Conclusions: A structured approach integrating travel history, focused examination, rapid diagnostics, and early recognition of high-risk features is essential to improving outcomes for febrile returning travelers. Strengthened vector control, enhanced vaccination uptake, and global surveillance are critical to reducing future disease burden. Full article

The genus Oncosiphon (Asteraceae), consisting of aromatic herbs, is indigenous to southern Africa. Oncosiphon species have been documented in Khoi-San ethnobotany as herbal remedies for typhoid fever, pneumonia, and as diuretics. Research on the biological properties and comprehensive phytochemical profiling of these important Oncosiphon species is currently limited. This study was therefore undertaken to address the knowledge void in chemical profiling, through the application of various analytical techniques to analyse the volatile and non-volatile constituents of three South African Oncosiphon species. The aerial parts of Oncosiphon suffruticosus (n = 28), O. grandiflorus (n = 16), and O. africanus (n = 4) were collected from various locations in the Western Cape Province of South Africa. The stems and leaves (SL) were separated from the flowers (F) and analysed as distinct samples. The methanol: chloroform (1:1, v/v) extracts were prepared and analysed using ultra–high–performance liquid chromatography quadrupole time-of-flight time–of–flight mass spectrometry (UHPLC–QToF–MS) and a semi–automated high–performance thin–layer chromatography (HPTLC) system. Multivariate data analysis was performed on the UHPLC–QToF–MS data to determine interspecies chemical variation. Two-dimensional (2D) gas chromatography (GCxGC–ToF–MS) was used to determine the headspace volatile profiles of the intact aerial parts. The results show that the non-volatile profiles of the Oncosiphon species are characterised by amino acids, phenolic acids, flavonoids, sesquiterpene lactones, and fatty acid derivatives. The HPTLC profiles of O. grandiflorus and O. africanus are chemically more closely related, and O. suffruticosus has a distinct profile, which is supported by the chemometrics results of the flowers. The major headspace volatile compounds in Oncosiphon flowers are α-pinene, α-ocimene, eucalyptol, o-cymene, and artemisia alcohol, whereas the stems and leaves mainly consist of α-ocimene, eucalyptol, and yomogi alcohol. Full article

Background/Objectives: Malaria remains a major cause of hospitalization in rural Madagascar, yet data on in-hospital clinical presentation, management, and patient outcomes remain limited. Methods: We conducted a three-year retrospective study (2023–2025) at a rural district hospital in Ambatoboeny, Madagascar, including patients of all ages hospitalized with malaria confirmed by rapid diagnostic testing and microscopy. Sociodemographic, clinical, laboratory, and treatment data were extracted from routine records. Length of hospital stay (LOS) was analyzed continuously and categorized as ≤2, 3–4, or ≥5 days. Seasonal admission patterns and factors associated with LOS were assessed using chi-square or Fisher’s exact tests, and associations with rainfall seasonality were explored using Spearman’s correlation. Results: Among 134 hospitalized patients, median age was 15 years (interquartile range (IQR) 7–25) and 52.2% were female. Plasmodium falciparum predominated (94.0%), while mixed-species infections were identified in 6.0% of cases; 20.1% of cases were classified as severe malaria, including 10.4% with cerebral malaria. Co-infections were frequent (52.2%), most commonly Schistosoma haematobium infection (14.2%) and typhoid fever (12.7%). Intravenous artesunate was initiated in 97.8% of patients; all received paracetamol and 94.8% received intravenous fluids. Median LOS was 2 days (IQR 2–3); 12.7% had prolonged hospitalization (≥5 days). Prolonged LOS was significantly associated with cerebral malaria, high parasitemia (≥5%), blood transfusion, and age < 15 years (all p ≤ 0.034), while co-infection and nutritional status were not. Conclusions: Hospitalized malaria in rural Madagascar presents with heterogeneous clinical phenotypes and a high burden of co-infections. Prolonged LOS is primarily driven by markers of severe disease and supportive care requirements, underscoring the need for early severity recognition and resource planning in low-resource hospitals. Full article

Background: Severe infectious diseases remain a preventable cause of adolescent mortality worldwide, yet global evidence focused on adolescence as a distinct life-course stage—and its vulnerability to health system disruption—remains limited. We examined long-term mortality rate trends, cause composition, and COVID-19–related changes among adolescents compared with late childhood. Methods: We analyzed Global Burden of Disease 2023 mortality estimates from 1990 to 2023 for six acute severe infectious causes: lower respiratory infections, meningitis, encephalitis, diarrhoeal diseases, typhoid/paratyphoid fever, and COVID-19. Analyses focused on adolescents aged 10–19 years, with children aged 5–9 years as a comparator. Mortality rates (per 100,000 population) were the primary metric. Trends were quantified using estimated annual percentage change (EAPC), and pre-COVID, COVID peak, and post-COVID periods were compared across Socio-demographic Index (SDI) categories. Results: From 1990 to 2023, mortality rates declined globally across all age groups; however, reductions among adolescents were consistently slower than those among children aged 5–9 years (EAPC −2.27% vs. −3.55% per year). Diarrhoeal diseases and typhoid/paratyphoid fever exhibited the steepest long-term declines, whereas lower respiratory infections and meningitis demonstrated slower reductions and maintained a substantial share of adolescent mortality risk. During the COVID-19 peak, mortality rates modestly increased among adolescents, while children continued their gradual decline. Mortality rates remained highest in low-SDI settings. Conclusions: Despite substantial global progress, severe infectious diseases continue to impose significant and inequitable mortality risk among adolescents. The persistence of a concentrated cause profile and the amplification of mortality during system disruption underscore adolescence as a vulnerable life-course stage requiring sustained prevention and resilient acute care systems. Full article

This paper investigates a fractional-order mathematical model for the co-infection dynamics of pneumonia and typhoid fever using the Liouville–Caputo derivative. We establish the existence, uniqueness, non-negativity, and boundedness of solutions using Banach’s fixed point theorem and fractional comparison principles. The Hyers–Ulam and generalized Ulam–Hyers–Rassias stability of the system are rigorously proved; this stability analysis is epidemiologically significant because it guarantees that small perturbations in initial conditions or model parameters—inevitable in real-world data collection—do not lead to unbounded deviations in disease trajectory predictions. To approximate solutions numerically, we develop a Laplace-Based Optimized Decomposition Method (LODM) and validate its convergence against a modified predictor–corrector scheme. The LODM provides a semi-analytical series solution, while the predictor–corrector method serves as a numerical benchmark; this dual approach ensures reliability of simulations. Numerical simulations illustrate the influence of the fractional order $\xi$ on system dynamics. Quantitative comparison between $\xi =1$ (integer order) and $\xi <1$ (fractional order) demonstrates that fractional modeling reduces peak infection by 12–18% and delays epidemic peaks by 15–30 days, confirming that memory effects capture long-term epidemiological dependencies that integer-order models fail to reproduce. A biological interpretation links the fractional order to immune memory, pathogen persistence, and intervention latency. This study provides both theoretical and numerical evidence supporting the use of fractional calculus in epidemiological modeling. Full article

Milk-borne outbreaks remain a significant issue in low-income countries due to unhygienic practices. Currently, there are no known easily accessible and low-cost diagnostic tests that can detect Salmonella enterica subsp. enterica serovar Typhi, the causative agent of typhoid fever, in raw milk samples at high specificity, sensitivity, and speed without preprocessing. Early detection of Salmonella enterica subsp. enterica serovar Typhi in food matrices is critical for preventing infection prior to consumption and reducing disease burden. Using colorimetric loop-mediated isothermal amplification, we screened 15 novel and two previously published primer sets. We identified one novel primer set capable of detecting the STY2879 gene in as few as 2000 genomes in 2% v/v raw milk reactions and 1000 genomes in 1% v/v raw milk reactions of Salmonella enterica subsp. enterica serovar Typhi after 30 minutes of incubation in a 65° C water bath. The colorimetric readout offers promising potential applications for on-site detection in remote and low-resource settings where infection with Salmonella enterica subsp. enterica serovar Typhi remains a public health concern. Full article

Background/Objectives: This study aimed to determine the antimicrobial susceptibility patterns of multidrug resistant (MDR) and extensively resistant (XDR) Salmonella enterica serovar Typhi (S. Typhi) strains among children, along with the associated behavioral and environmental risk factors across different population groups in multiple districts of Punjab, Pakistan. Methods: A cross-sectional study was conducted across 20 districts in Punjab, Pakistan. Structured questionnaires were used to assess sociodemographic and behavioral determinants. Blood cultures from febrile children were obtained for the isolation and identification of S. Typhi, followed by antimicrobial susceptibility testing and screening for the resistance genes. Results: A total of 900 blood samples were collected and 41.5% were positive for S. Typhi. The proportion of culture-positive cases were higher among children aged 6–12 years (34.8%). Sociodemographic and behavioral analysis revealed that children from low-income households (PKR < 20,000 showed significantly higher infection rate (67.1%, p < 0.001). Antimicrobial susceptibility testing revealed high resistance rates against several antibiotics: Ciprofloxacin (88.8%), Trimethoprim/sulfamethoxazole (83.7%), Ampicillin (73.8%) and Chloramphenicol (72.7%). However, all isolates remained susceptible to carbapenems and azithromycin. The prevalence of MDR and XDR S. Typhi in urban areas was 28.1% and 60.8%, respectively, while rural areas showed 22.6% MDR and 20.6% XDR. In contrast, nomadic populations exhibited a higher rate of MDR (49.3%) but a lower XDR prevalence of 18.6% with significant geographic variations in resistance patterns. Molecular analysis revealed a high prevalence of resistance genes, including sul1 (83.7%), sul2 (79.7%), followed by dfrA7 (81.3%), catA1 (64.9%) and bla_TEM (60.5%), bla_CTX-M-1 (12.5%), bla_CTX-M-15 (25.9%) and qnrS (88.8%), respectively. Conclusions: The study underscores a persistent typhoid burden and widespread antimicrobial resistance among children in Punjab. Targeted vaccination, antibiotic stewardship, public health education are urgently needed, especially among the nomadic population, where healthcare access and hygiene awareness are limited. Full article

Central nervous system (CNS) infections caused by Salmonella species (spp.) are exceptionally rare in adults but are associated with significant morbidity and mortality, particularly in immunocompromised individuals. Clinical presentation is often nonspecific, including fever, headache, or altered mental status, while imaging may demonstrate meningeal enhancement, abscesses, or cytotoxic lesions. We present a systematic review of non-typhoidal Salmonella spp. infections involving the CNS across various immunosuppressive contexts, illustrated by the case of a 38-year-old HIV-positive man with well-controlled infection. He developed disseminated Salmonella enterica infection, with bacteremia, septic arthritis, and ultimately corpus callosum involvement, following chronic self-administration of corticosteroids for cluster headaches. This case underscores that corticosteroid exposure can precipitate systemic dissemination even in patients with preserved CD4 counts. Although this condition carries a high risk of mortality, early recognition, targeted antibiotic therapy, and careful multidisciplinary management of underlying immunosuppression are critical to improving survival and minimizing neurological sequelae. Full article