Volume 34, Issue 1, 2026
Review
Investigating the dual nature of Clostridium botulinum: pathogenic mechanisms and therapeutic potentials
Soleymanpour Kosar,
Zeinalzadeh Elham,
Ganbarov Khudaverdi,
Asgharzadeh Mohammad,
Kafil Hossein Samadi
Background: Clostridium botulinum (C. botulinum) is known for producing one of the strongest neurotoxins, namely botulinum neurotoxin (BoNT). This toxin is responsible for causing botulism, which is considered a severe neurological disease.
Objectives: This comprehensive narrative review highlights the dual nature of C. botulinum as both a serious health threat and a groundbreaking therapeutic agent. Methods: A comprehensive literature search was conducted in Google Scholar, PubMed/Medline, and Scopus (1971–2025, 2020–2025 literary focus) using keywords related to botulism pathogenesis, clinical features, and therapeutic approaches.
Results: Key findings indicate that, despite advancements in botulism management and reduced mortality due to heptavalent botulinum antitoxin (HBAT) and botulism immune globulin intravenous (BIG-IV) antitoxins, diagnostic challenges and bacterial spore resistance, particularly in group I, remain persistent. On the other hand, the discovery of serotype BoNT/X with lower toxicity in vertebrates and unique capabilities has opened new horizons in the design of safer treatments.
Conclusions: C. botulinum represents a remarkable paradox in biology, an organism capable of producing one of the deadliest toxins known, yet simultaneously a cornerstone in modern therapeutic innovation. In fact, this toxin's dual nature is based on its selective targeting of BoNTs. In this regard, the systemic entry and distribution of this poison in the body - or, in other words, intoxication with it - poses a life-threatening aspect. On the other hand, the use of this bacterium's toxin for therapeutic and medicinal purposes is progressing due to its topical and controlled administration and entry into the body make it a targeted and effective therapeutic tool in the field of medicine. A better and more precise understanding of the mechanisms of action and, if necessary, future structural and engineered modifications in the toxin could lead to the emergence of a new generation of BoNTs that hold promise for the development of esthetic and therapeutic applications in medicine.
Neurological Infections in HIV: A Case-Based Review for Clinicians
Gupta Nitin,
Bhat Bela,
Das Adhikari Shreya,
Singh Sonali,
Malla Sundeep,
Boodman Carl,
Varma Muralidhar,
Grobusch Martin P.,
Kumar Tirlangi Praveen
Central Nervous System (CNS) disease remains a significant cause of morbidity and mortality in people with advanced HIV infection. This case-based review presents eight illustrative scenarios to demonstrate a structured clinical approach to common CNS manifestations in HIV in low-resource settings. The cases cover meningeal syndromes (cryptococcal and tuberculous meningitis), focal mass-like lesions (toxoplasmosis, tuberculoma, and primary CNS lymphoma), and diffuse or multifocal white matter disorders (HIV encephalopathy, progressive multifocal leukoencephalopathy, and cytomegalovirus encephalitis). Each case highlights key clinical reasoning steps, including interpretation of neuroimaging and cerebrospinal fluid analysis, and integration of serologic and molecular diagnostics. A syndromic framework is used to classify presentations and refine the differential diagnosis based on CD4 count, rate of progression, and radiological patterns. The review also discusses principles of management, including targeted antimicrobial or oncologic therapy, timing of antiretroviral therapy initiation, and the prevention and treatment of immune reconstitution inflammatory syndrome. Through these illustrative examples, the article provides a practical, context-appropriate guide to evaluating and managing HIV-associated CNS disease, particularly in settings where diagnostic resources and access to surgical interventions may be limited.
Pulmonary edema in Dengue: a systematic review and meta-analysis
Mehta Rachana ,
Bhattarai Abhinav,
Sah Ranjit,
Shamim Muhammad Aaqib,
Srivastava Shriyansh,
Mohanty Aroop,
Luna Camila,
Bonilla-Aldana D. Katterine,
Feehan Jack,
Apostolopoulos Vasso,
Rodriguez-Morales Alfonso J.
Background: Pulmonary edema is a potentially life-threatening complication of dengue. The recorded incidence of pulmonary edema has varied widely between studies. Therefore, we aimed to systematically review the literature on this topic and, through meta-analysis, estimate the pooled incidence of pulmonary edema in dengue using published data.
Methods: A systematic search of the PubMed, Scopus, and Web of Science databases was conducted from January 2000 to February 2025, in accordance with the PRISMA 2020 guidelines. Studies reporting the incidence of pulmonary edema in patients with dengue were included. Pooled incidence estimates for pulmonary edema in dengue were calculated via meta-analysis in R version 4.3.2 using a random-effects model.
Results: Our search revealed 432 results, of which five studies met our inclusion criteria. The incidence of pulmonary edema among dengue patients varied across studies, ranging from low to moderate. We observed minimal risk of bias across studies. Our meta-analysis found a pooled incidence of pulmonary edema in dengue of 9.14% [95% CI = 6.98%-11.89%].
Conclusion: Our investigation suggests that a non-negligible proportion of dengue patients may develop pulmonary edema. Acknowledging the risk of pulmonary edema and monitoring it are essential to ensuring effective prevention of pulmonary morbidity in dengue. Additionally, we suggest that clinicians assess for underlying dengue infection when managing pulmonary edema, particularly in regions at high risk.
Vaginal microbiota and urinary tract infections in women: the protective role of vaginal lactobacilli in counteracting urinary tract infections occurrence and recurrence
Moriconi Francesco,
Pelagagge Margherita,
Bertini Marco
Urinary Tract Infections (UTIs) are common clinical conditions. Women are affected by UTIs more than men and their probability of experiencing such conditions is high (60%). The vagina and its defensive system play a key role in the pathogenesis of UTIs, making the vaginal microbiota (VMB) a target for controlling UTIs and their recurrence (rUTIs). Current therapy consists of low-dose antibiotics for rUTIs prevention. The increasing incidence of antimicrobial resistance documented to date has rendered this strategy less attractive. The initial step of UTIs pathogenesis involves colonization of the vaginal introitus and periurethra by uropathogens. The following steps may include the ascension of uropathogens via the urethra to the bladder and kidneys. Vaginal infections may be caused by uropathogens from the intestinal microbiota, taking advantage of the proximity between the anus and the vagina. Nevertheless, uropathogens may arise from the vagina itself because of alterations in VMB. Changes in VMB lead to Bacterial Vaginosis (BV), which consists of the replacement of healthy lactobacilli with unhealthy Gram-negative bacteria, such as Escherichia coli. The documented relationship between BV and UTIs supports the intriguing hypothesis that restoring VMB may represent a new option to control UTIs and rUTIs after short-term antibiotic treatment in a safe and cost-effective manner.
Original article
Optimization of Nested-PCR for the detection of Plasmodium malariae in laboratory settings in Southern Vietnam
Nguyen Kim Trung,
Nguyen Ngoc Hieu,
Dinh Quoc Long,
Nguyen Hoang Linh Vu,
Nguyen Minh Anh Thi,
Huynh Hong Quang,
Tran Hue Van Thi
Nested Polymerase Chain Reaction is a highly effective technique for detecting infectious diseases, particularly in cases involving low level of parasitemia infections such as malaria. Objective: This study aimed to optimize a Nested-PCR protocol for the specific detection of Plasmodium malariae, with a defined scope focused on refining cycling conditions, annealing parameters, and procedural steps to ensure reliable performance in laboratory settings in Southern Vietnam.
Methods: The assay targeted the P. malariae 18S rRNA gene using PLU5/PLU6 and MAL1/MAL2 primers. Cycle numbers were optimized at 25, 30, and 35 in the first round, and 25 and 30 in the second round. The annealing temperature for MAL1/MAL2 primers were evaluated from 54 to 60°C, and PCR products were visualized using the ChemiDoc-It² system. Results: The MAL1/MAL2 primer pair demonstrated high specificity for P. malariae, with no amplification observed for other Plasmodium species (including: P. falciparum, P. vivax, P. ovale and P. knowlesi) or common microbial contaminants. The optimal conditions were determined to be 35 cycles in the first PCR round, 25 cycles in the second round, with an annealing temperature of 54°C for the MAL1/MAL2 primers. The protocol achieved a limit of detection as low as 0.5 parasites/µL.
Conclusions: The optimized protocol is well-suited for laboratories in Southern Vietnam.
Genomic epidemiology of Carbapenem-Resistant Enterobacterales in southern Vietnam: dominance of Klebsiella pneumoniae ST16 and horizontal gene transfer
Truong Thien Phu,
Tran Trong Tin,
Le Phuong Mai,
Nguyen Van Thanh,
Ta Tuan Khanh,
Tran Thi Tuyet,
Tran Cong Tri,
Le Pham My Da,
Nguyen Quang Tin,
Nguyen Thi Nam Phuong
Background: Carbapenem-resistant Enterobacterales (CRE) pose a critical global threat. However, the genomic epidemiology, transmission dynamics (clonal vs. horizontal gene transfer), and mechanisms driving co-resistance in Southern Vietnam remain poorly understood. This study aimed to use Whole-Genome Sequencing (WGS) to characterize the molecular epidemiology, transmission mechanisms, and co-resistance patterns of CRE from a major referral center in Southern Vietnam
Methodology: We performed a cross-sectional study using whole-genome sequencing on 189 CRE isolates (K. pneumoniae, E. coli, E. cloacae) from a major referral hospital in Southern Vietnam. We analyzed Carbapenemase-Producing Genes (CPGs), MLST, colistin resistance mutations, plasmid clusters, and co-carried AMR genes.
Results: K. pneumoniae ST16 (n=67, 35.4%) was the most frequently identified clone, detected in 10/12 ward strata. We identified two distinct colistin resistance pathways linked to CPG lineage: blaKPC/blaOXA-48 family clones (ST147, ST5815, ST11) showed a universal prevalence of chromosomal pmrB mutations (n=55/55, 100%), whereas the blaNDM clone (ST16) exhibited a low frequency of these mutations (6.0%). Analysis of 10 plasmid clusters carrying CPGs revealed the frequent co-carriage of qnrS1 (quinolone resistance) and rmtB1 (amikacin resistance).
Conclusions: CRE dissemination in Southern Vietnam is driven by a dual-transmission scenario. We identified distinct CPG-linked colistin resistance pathways and significant co-carriage of qnrS1 with CPGs. This highlights the potential risk of co-selection through antibiotic pressure. These findings underscore the urgent need for surveillance strategies targeting high-risk clones like K. pneumoniae ST16.
Racial Disparities in People Living with Human Immunodeficiency Virus and Upper Gastrointestinal Bleeding: A Nationwide Study (2016-2021)
Ravikumar Diviya Bharathi,
Yellappa Naveen,
Sivasubramanian Barath Prashanth,
Saiyad Falaknaaz Mubassirhusen,
Murali Mathangi,
Shah Heer Pareshbhai,
Mavani Dency Dineshbhai,
Adepu Neha Nanditha,
Patel Jay,
Memon Uzer Abdulaziz,
Sakalabaktula Krishna Sai Kiran,
Endreddy Anusha,
Basumani Karthik,
Tirupathi Raghavendra,
Dalal Rutul
Background: In the United States, approximately 1.2 million people were living with HIV (PLWH) by the end of 2021, with African Americans experiencing a higher mortality rate than American Whites (20.1 per 100,000 vs 3.1 per 100,000). Upper gastrointestinal bleeding (UGIB), though uncommon (1–14%), is a serious concern. Data on UGIB among PLWH is limited.
Methods: A retrospective cross-sectional analysis was conducted using the National Inpatient Sample database (2016-2021). PLWH with age ≥18 years with UGIB were identified using ICD-10 codes. Multivariate regression was used to determine mortality risk by adjusting for sociodemographic factors and comorbidities.
Results: Among 6,923 PLWH with UGIB requiring ICU-level care, mortality was higher in AA than AW (37.1% vs 29.9%). AA had a higher mortality risk than AW (p<0.05). Among those who underwent endoscopy, the mortality risk remained higher in AA compared to the AW (p=0.1). However, early endoscopy (<24 hours of admission) showed a lower mortality rate in AA compared to AW (41.7% vs 45.8%), but the difference was not significant after adjustment (p>0.05). In the AA cohort, comorbidities such as variceal gastrointestinal bleed, solid malignancy, acute coronary syndrome, acute kidney injury, sepsis, pancytopenia, and invasive ventilation independently increased the mortality risk (p≤0.05).
Conclusions: African Americans with upper gastrointestinal bleeding were associated with increased mortality compared to American Whites. These findings underscore the need for equitable healthcare and targeted strategies to identify and address barriers in this population.
Clinical characteristics of community acquired pneumonia due to Mycoplasma pneumoniae: experience from an outbreak
Nair Aparna Anil,
Niyas Vettakara Kandy Muhammed,
Ananthanarayanan Rajalakshmi,
Durai Shijukumar Chella,
Jose Divakar,
Padmanabhan Arjun
Background: Mycoplasma pneumoniae is a major cause of Community-Acquired Pneumonia (CAP) but often remains underrecognized because it requires molecular or serologic testing for diagnosis. In late 2024, an increase in cases with poor response to macrolides was noted at a tertiary hospital in Thiruvananthapuram, Kerala. This study describes the clinical profile, treatment, and outcomes of patients affected during this outbreak.
Methods: This retrospective study included all patients admitted with M. pneumoniae pneumonia between January 2024 and August 2025. Diagnosis was confirmed by PCR or IgM serology. Clinical features, laboratory parameters, radiologic findings, treatment, and outcomes were collected from records and analyzed using Jamovi (version 2.6.45).
Results: A total of 124 patients were included; 79.8% were <18 years (median age 9 years, IQR 6–14). Diagnosis was PCR-based in 97.6%. Cough (97.6%) and fever (95.2%) were the most common symptoms. Nineteen patients (15.3%) required supplemental oxygen, three (2.4%) non-invasive ventilation, and five (4.0%) invasive mechanical ventilation. Pleural effusion was noted in 24.2%. Extrapulmonary complications were rare, including one case each of encephalitis and pericardial effusion. Definitive therapy included doxycycline in 76.6%, azithromycin in 17.7%, and levofloxacin in 3.2%. One-third of patients initially started on macrolides required a change to alternative agents. Corticosteroids were used in 18.5%, and 33.0% required ICU care. Three patients (2.4%) died, all with significant comorbidities.
Conclusions: During the 2024–2025 outbreak, M. pneumoniae caused predominantly paediatric CAP but occasionally severe disease requiring intensive care. The frequent need to switch from macrolides suggests emerging resistance. Early recognition and use of alternative agents such as doxycycline or fluoroquinolones may improve outcomes.
Enterovirus respiratory infection in adults: an overlooked clinical burden emerging in the post-pandemic era
Venturini Sergio,
Reffo Ingrid,
Messina Andrea,
del Fabro Giovanni,
Zanus-Fortes Agnese,
Callegari Astrid,
Giovagnorio Federico,
Negri Camilla,
Basaglia Giancarlo,
Corich Lucia,
Zuccon Umberto
Enterovirus (EV) is increasingly identified as a cause of acute respiratory infections in adults, yet its clinical burden in real-world settings remains poorly characterized. Individuals with underlying chronic respiratory conditions, such as asthma or chronic obstructive pulmonary disease, are at heightened risk of severe respiratory compromise from EV infection, as they are from many other respiratory pathogens.
Following an increase in EV circulation in our healthcare district in recent years, as reported in other Countries, we performed a retrospective analysis of all adults (≥18 years) including only acute respiratory EV infection documented by multiplex RT-PCR of nasopharyngeal swabs between January and December 2024. Seventy patients were included (mean age 68.5 ± 19.2 years, balanced sex distribution) with a high prevalence of comorbidities, particularly cardiovascular disease (37%) and chronic respiratory disease (34%). The clinical presentation was dominated by cough (74%) and dyspnea (70%), whereas fever was less common. At presentation, 41% (n=29) met criteria for acute respiratory failure, defined as a partial pressure of oxygen <60 mmHg on arterial blood gas. Chest radiography was abnormal in most cases (74%), showing predominantly interstitial markings (51%), followed by consolidations (16%) and mixed patterns (7%). Inflammatory markers were frequently elevated, with C-reactive Protein ≥0.5 mg/dL in 93.7% and leukocytosis in 44.3%. Forty patients (57%) required hospital admission, 35 (50%) needed oxygen or ventilatory support (predominantly low-flow oxygen), and seven patients (10%) required escalation to advanced support (high-flow oxygen in four cases, non-invasive ventilation in two, and invasive mechanical ventilation in one). Two patients (2.8%) were admitted to the Intensive Care Unit, and 30-day mortality was 2.8% (n=2). In our cohort, patients with COPD (n = 14) had the most severe course (respiratory failure 57%, oxygen requirement 64%, hospitalization 71%, 1 IMV, 1 death), whereas those with asthma (n = 7) had a comparatively milder clinical course (respiratory failure 43%, no ventilatory support, no deaths).
Overall, in our real-world scenario, EV infection was associated with frequent gas-exchange impairment, radiographic abnormalities, and clinically meaningful resource utilization in adults, particularly among those with chronic respiratory disease.
Risk factors associated with carbapenem-resistant Enterobacterales infections in hospitalized patients: A case-control study
Zambrano-Calderero Vivian,
Vera-Álava Fabricio,
Borges Marcio
Background: Carbapenem-Resistant Enterobacterales (CRE) represent a critical public health threat.
Aim: To analyze risk factors for CRE infections in adults at a tertiary hospital in Manta, Ecuador, during 2022.
Methodology: A case-control study (27 cases; 193 controls) compared CRE versus Carbapenem-Susceptible Enterobacterales (CSE). Univariable and Multivariable Firth logistic regression was performed to adjust for small-sample bias.
Results: In multivariable analysis, time to infection onset was the most consistent predictor of CRE (aOR: 1.08; 95% CI: 1.03–1.12; p=0.001). Other significant risk factors included chronic corticosteroid therapy (aOR: 43.10; 95% CI: 3.04–611.96; p=0.005), prior hospitalization (aOR: 14.52; 95% CI: 2.22–94.86; p=0.005), urinary catheter (aOR: 10.39; 95% CI: 2.20–49.00; p=0.003) and central venous catheterization (aOR: 13.46; 95% CI: 1.30–139.45; p=0.029). Nosocomial origin (aOR: 0.05; 95% CI: 0.003–0.86; p=0.039), and Internal Medicine management (aOR: 0.23; 95% CI: 0.06–0.94; p=0.041) showed protective associations.
Conclusions: In this setting, the cumulative duration of healthcare exposure (time to infection onset) was the primary driver of CRE risk. However, these risk factors are highly context-dependent and vary across different populations and facilities. Therefore, these results cannot be generalized, highlighting the need for localized surveillance and further multicenter studies to understand regional resistance dynamics.
Case report
Cedecea lapagei pneumonia: the first reported case in Italy and literature review
Ielo Simone,
Camarlinghi Giulio,
Salvadori Elisa,
Dilroba Akter,
Parisio Eva Maria,
Scala Raffaele
Cedecea lapagei is a rare Gram-negative bacillus of the Enterobacteriaceae family, typically identified as an opportunistic pathogen in immunocompromised or critically ill patients. Less than twenty clinically significant infections have been described worldwide, many displaying concerning multidrug-resistance profiles. We report the first documented case of C. lapagei pneumonia in Italy, occurring in a 73-year-old man with hypogammaglobulinemia and post-stroke dysphagia who presented with a recurrence of pneumonia. Bronchoalveolar Lavage Fluid (BALF) obtained for diagnostic clarification yielded C. lapagei as the causative organism. A literature review on C. lapagei pneumonia has been conducted as well. This case underscores the pathogenic potential of C. lapagei in vulnerable hosts and highlights the importance of thorough microbiological investigation and targeted antimicrobial therapy, given its unpredictable and often extensive antimicrobial resistance pattern.
The Infections in the History of Medicine
Infectious threats during the Portuguese exploration of West Africa in the 15th and 16th centuries
Matta Silvia,
Sao Miguel Morgado Mariana,
Donghi Lorenzo,
Braidotti Luca,
Gobbo Ylenia,
Di Bella Stefano,
Simonetti Omar
The Portuguese exploration of sub-Saharan Africa in the 15th and 16th centuries marked a crucial point both for geographical discovery and for the development of early naval medicine. This article looks at the health challenges faced by explorers from the time of Henry the Navigator (1394-1460) onwards, focusing on the infectious diseases that emerged on first contact with West Africa. Italian explorers such as Alvise Cadamosto and Antoniotto Usodimare provided valuable accounts of early expeditions in which they emphasized the occurrence of febrile diseases in the swampy coastal regions. These encounters showed the double threat of infections on board and off the ship. The article also highlights the Portuguese response to the pathogenic barriers encountered. While medical care was initially neglected, the continuing loss of labour prompted the empire to gradually deploy medical professionals on board and in the colonies. Over time, Portugal established hospitals and lazarettos and standardised medical training and licensing under King Manuel I. These early efforts to formalise medical care laid the foundations for colonial healthcare systems and early forms of public healthcare. Although these adaptations are still a long way from modern tropical medicine, they represent fundamental steps towards organised health care in the overseas territories and reflect the shift from pure exploration objectives to institutionalised support for the survival of imperial ventures.
Letters to the editor
Australian bat lyssavirus and the long shadow of rabies: lessons from the History of Medicine
Galassi Francesco Maria,
Vaccarezza Mauro,
Vitale Marco,
Galli Massimo,
Varotto Elena
Not available
