Volume 33, Issue 2, 2025
Review
Antigen recognition and immune response to monkeypox virus infection: implications for Mpox vaccine design – a narrative review
Abebaw Desalegn,
Akelew Yibeltal,
Adugna Adane,
Hibstu Zigale,
Tegegne Bantayehu Addis,
Fenta Abebe,
Amare Gashaw Azanaw Amare,,
Jemal Mohammed,
Baylie Temesgen,
Atnaf Aytenew
Monkeypox virus (MPXV) is a DNA virus from the Orthopoxvirus genus, sharing significant genomic similarity with the variola virus that causes smallpox. The cessation of smallpox vaccinations has contributed to recent Mpox outbreaks, with reduced immunity levels, particularly in younger populations born after the vaccine was discontinued. The virus triggers innate and adaptive immune responses, with toll-like receptors (TLRs) playing a key role in recognizing viral components and activating proinflammatory cytokines. However, MPXV evades the immune system by producing proteins that inhibit immune signaling pathways. Natural killer (NK) cells and interferons are crucial for early defense, but MPXV impairs their function. Adaptive immunity involves robust antibody and T-cell responses, similar to smallpox vaccination responses. Various mRNA-based candidate vaccines have demonstrated strong immunogenicity, with preclinical studies confirming their ability to trigger potent B-cell and T-cell responses. However, the genetic changes observed in the current outbreak strains necessitate ongoing surveillance of MPXV mutations and their impact on immunogenic proteins. This review aimed to summarize current insights into antigen recognition and immune responses to MPXV, with a focus on key antigenic proteins relevant to vaccine development.
Clinical profile and outcomes of pulmonary nocardiosis in India: a systematic review of individual cases
Sebastian Anjely,
Kumar Tirlangi Praveen,
Vinod Kutty Sharada ,
Kiran Pothumarthy Venkata Swathi,
Gupta Mukund,
Gupta Nitin
Introduction: Nocardiosis is a common cause of pneumonia in immunocompromised individuals. Limited data regarding its epidemiology, clinical presentations, and outcomes in India are available. This systematic review analysed the clinical profile and outcomes of pulmonary nocardiosis in India.
Methods: We systematically reviewed individual cases of culture-confirmed pulmonary nocardiosis from India published between January 1960 and May 2024 using the PubMed, Embase, and Web of Science databases. Studies lacking microbiological confirmation or detailed clinical data were excluded. Descriptive statistics were used to summarise demographic, clinical, and microbiological data, while chi-square and t-tests assessed differences between mortality and survival groups.
Results: The review included 109 cases from 67 studies. Male predominance (74.1%) was observed, with a mean age of 49.6 ± 16.9 years. Diabetes (26.6%), steroid use (51.4%), and chronic lung disease (37.8%) were key risk factors. Nocardia otitidiscaviarum (38.4%) was the most common species identified. Mortality was noted in 26% of the patients. Cotrimoxazole resistance and lack of cotrimoxazole use for treatment were associated with mortality.
Conclusions: Pulmonary nocardiosis presents diagnostic and therapeutic challenges in India, with high resistance rates and significant mortality. Improved diagnostic methods and region-specific treatment strategies are essential.
Zosurabalpin: an antibiotic with a new mechanism of action against carbapenem-resistant Acinetobacter baumannii
Terzi Irene,
Panagopoulos Periklis,
Rafailidis Petros
Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) poses a critical global health threat, particularly among hospitalized and critically ill patients, due to its association with severe, difficult-to-treat infections. Its high resistance stems from genomic plasticity, biofilm formation, and environmental persistence, leading to limited treatment options and high mortality. Existing treatments often rely on sulbactam-based combinations, yet resistance continues to rise and new agents remain limited.
Aims: This review aims to highlight the therapeutic potential of zosurabalpin, a first-in-class lipopolysaccharide (LPS) transport inhibitor with selective activity against A. baumannii, by summarizing preclinical and early clinical data on its efficacy, mechanism of action, pharmacokinetics, and safety.
Sources: Peer-reviewed publications from PubMed and Scopus, clinical data from ClinicalTrials.gov, and relevant conference materials ECCMID and IDWeek.
Content: Zosurabalpin inhibits the LptB-FGC complex, blocking LPS transport and causing lethal intracellular accumulation. Preclinical data demonstrate potent in vitro and in vivo activity against CRAB, with high selectivity and favorable pharmacokinetics. Phase 1 studies report good tolerability and a promising safety profile. Its novel mechanism makes zosurabalpin a strong candidate for treating CRAB.
Implications: With rising resistance and limited effective treatments, zosurabalpin offers a new, targeted therapeutic approach. Continued clinical development could help close a critical gap in the management of multidrug-resistant Acinetobacter baumannii.
Original article
Unmasking the Hidden Hurdles in Outpatient Parenteral Antibiotic Therapy using a lean six-sigma approach
Keri Vishakh C.,
Ali Sajjad,
Elattma Ahmed,
Dhar Sorabh,
M. Lea
Background: Implementing Outpatient Parenteral Antimicrobial Therapy (OPAT) safely poses significant challenges, particularly in centers without a dedicated OPAT team, where monitoring by infectious diseases (ID) physicians can be difficult. We utilized a Lean 6-Sigma framework to evaluate our OPAT process and define opportunities for improvement.
Methods: In a retrospective cohort study, we screened 5 months of ID consult data for patients who left on OPAT from an urban hospital system. Primary outcome was incidence of adverse event (AE), a composite of either emergency department (ED) visit or all-cause 30-day readmission. Clinical characteristics and completeness of ID documentation were compared between patients with and without an AE. Complete documentation included antibiotic dose, duration, stop date, and a scheduled ID appointment. We simultaneously conducted a 6-sigma analysis involving stakeholders (physicians, case managers, nurses) in focus groups, to generate a process map, Ishikawa diagram, 5-Why’s analysis, and identify heterogeneity in our OPAT process.
Results: Fifty of 441 patients (11.3%) were discharged on OPAT and incidence AE was 30%. Neither type of infection, nor demographics, clinical characteristics, or discharge location differed between groups. Only half (50%) of the patients had complete documentation. Median time from discharge to clinic was 21 days, however, AE’s occurred in a median time of 12 days. Patients without an AE were more likely to have been seen in the clinic post-discharge (51% versus 20%, p=0.039). ID clinic appointments were made for 60% of patients, with a show rate of 63%. Two additional unscheduled patients initiated their own visit. The 6-Sigma analysis identified process heterogeneity at discharge location and over-reliance on human memory for complete documentation. Interestingly, focus groups revealed numerous assumptions not supported by the objective data.
Conclusions: Almost 1 in 3 patients leaving on OPAT experienced an adverse event. A 6 Sigma analysis identified heterogeneity in our process and incorrect assumptions among stakeholders. Next steps should focus on improving ID documentation and ensuring all patients leaving on OPAT have an ID clinic visit scheduled within 14 days after discharge.
Self-perceived stigma in people living with HIV in Spain: a mixed-methods study
Picón-Jaimes Yelson Alejandro,
Lozada-Martínez Ivan David,
Rosàs Tosas Mar,
Tiraboschi Juan
Introduction: Despite medical advances, stigma against people living with HIV remains a major issue, especially in healthcare. Factors like ignorance and lack of training contribute to discrimination; studies show stigma varies by setting and provider background. This study in Spain aimed to explore self-perceived stigma and its impact on healthcare access.
Methods: This mixed-methods study in Spain assessed self-perceived stigma among people living with HIV using a validated questionnaire and semi-structured interviews. Participants were recruited via social media and public announcements. Data analysis involved statistical tests and qualitative coding. Ethical approval was obtained, ensuring confidentiality and compliance with European regulations.
Results: The study included 525 participants, mostly men (53.3%), with a median age of 38 years and an average of four years since diagnosis. The majority (96.2%) received care through the public healthcare system.
Stigma levels varied; internalised stigma was low, with most rejecting negative feelings about living with HIV. However, anticipated and experienced stigma remained, particularly in healthcare settings, where many reported discrimination and neglect—findings corroborated in interviews. Avoiding physical contact with patients and the excessive use of barrier measures were common behaviours. Analysis showed that stigma decreases with age and time since diagnosis but is higher among non-binary individuals.
Conclusions: This study highlighted varying levels of stigma affecting people living with HIV, particularly in healthcare. While internalised stigma was low, many anticipated or experienced discrimination, often due to impersonal treatment and unfounded fears, emphasising the need for education and awareness to foster respectful, empathetic care.
High Mortality and Antimicrobial Resistance: Challenges of Bloodstream Infections in Liver Transplant Recipients
Brescini Lucia,
Gelo Signorino Gabriele,
Montalti Roberto,
Pallotta Francesco,
Morroni Gianluca,
Nicolini Daniele,
Mocchegiani Federico,
Vivarelli Marco,
Svegliati-Baroni Gianluca,
Tavio Marcello,
Cerutti Elisabetta,
Giacometti Andrea,
Barchiesi Francesco
Purpose: Bloodstream infections (BSIs) are one of the most frequent complications among liver transplant recipients and are associated with a markedly increased risk of death. Our study aims to define the incidence, epidemiology and clinical characteristics of BSIs after liver transplantation (LT) and to investigate risk factors related to 30-day mortality.
Methods: We considered all patients who underwent LT at the Università Politecnica delle Marche of Ancona for up to 10 years and selected those who experienced at least one episode of BSI.
Results: Out of 601 LT recipients, 96 had at least one episode of BSI. Most BSIs occurred within the first month post-transplantation. Central vascular catheter infections were the most frequent source, followed by surgical site infections, pneumonia, and urinary tract infections. Overall, we isolated 102 microorganisms: 66% were Gram-negative bacteria, 30% Gram-positive bacteria and 4% fungi. High rates of antimicrobial resistance were observed among both Gram-negative (34%) and Gram-positive bacteria (84%).
Thirty-day mortality was 26%, with septic shock (HR 226.980 [CI 95% 5.083-10135.347], p = 0.005), the absence of invasive procedures within 72 hours before BSI onset (HR 88.567 [CI 95% 2.484-357.754], p = 0.014), white blood cell count ≥ 2,500/mmc (HR 34.948 [CI 95% 1.568-778.750], p = 0.025), creatinine > 1.02 mg/dl (HR 13.982 [CI 95% 1.487-131.485], p = 0.021] and hypoalbuminemia (HR 24.775 [CI 95% 1.371-447.744], p = 0.030) being significant risk factors.
Conclusions: This study provides detailed insights into post-transplant BSIs, highlighting the alarming rates of antimicrobial resistance, thereby suggesting a major effort to rationalize the use of antimicrobial therapy.
High prevalence and risk factors of positive sputum smear in newly diagnosed pulmonary tuberculosis patients in Vietnam
Tran Xuan Thuy,
Duong Khanh Linh,
Bui Duc Manh,
Dang Khanh Linh,
Hoang Nang Trong,
Bui Thi Han,
Gautret Philippe,
Dao Thi Loi,
Hoang Van Thuan
Objectives: To assess the prevalence and identify risk factors associated with smear-positive tuberculosis (acid-fast bacilli [AFB]-positive) in newly diagnosed patients in Vietnam. Methods: A retrospective study was conducted on patients newly diagnosed with pulmonary tuberculosis (PTB) from August 2023 to August 2024. Patients were classified as smear-positive if at least one respiratory sample tested positive with AFB before starting anti-tuberculosis treatment. Smear-negative individuals had to submit a minimum of two sputum samples, all of which had to test negative before treatment initiation.
Results: 379 PTB patients were included with 48.3% being AFB-positive. The proportion of hemoptysis was significantly higher in AFB-positive than in AFB-negative patients (9.8% versus 4.1%, p = 0.04). AFB-negative patients had a significantly higher rate of fatigue and crackles compared to AFB-positive patients with 85.7% versus 77.0%, p = 0.03 and 36.2% versus 25.7%, p = 0.03, respectively. Cavitary lung lesions were significantly more common in AFB-positive patients (48.6% versus 29.1%, p<0.0001). In multivariate analysis, patients with diabetes mellitus and those with long-term corticosteroid use were respectively three times and six times more likely to be AFB-positive (OR = 2.71, p = 0.002 and OR = 6.15, p = 0.009) more likely to. Cavitation in chest-x-ray was also associated with 2.5 times of risk for smear-positive (OR = 2.53, p <0.0001). All of three HIV-coinfected patients were AFB-negative.
Conclusion: Our findings emphasize the importance of screening and early diagnosis of PTB in individuals with diabetes mellitus and in those on long-term corticosteroid therapy. Strengthening TB control efforts, particularly among high-risk populations, is crucial to reducing the burden of smear-positive TB and preventing further transmission.
Case report
Rare case of urinary tract infection caused by Cedecea lapagei in a 93-year-old patient in southern Italy
Aveta Achille,
Napodano Giorgio,
Spena Gianluca,
Contieri Roberto,
Perdonà Sisto,
Pinchera Biagio,
Pandolfo Savio Domenico
Cedecea lapagei is a rare Gram-negative bacterium that has been infrequently associated with human infections. It is a non-encapsulated, facultative anaerobic organism that grows well in nonselective laboratory media and exhibits variable resistance patterns. Although Cedecea lapagei has been identified as a pathogen since 2006, reports of its clinical significance remain scarce, particularly in Europe. Here, we present the case of a 93-year-old male from Southern Italy, with multiple comorbidities and a history of urinary catheterization, who developed a urinary tract infection (UTI) caused by Cedecea lapagei. The patient was successfully treated with ciprofloxacin and fosfomycin, achieving clinical and microbiological healing. This report examines the substantial challenges associated with rare pathogens in clinical practice, focusing on the critical need for prompt and precise identification alongside tailored treatment strategies. Additionally, it highlights the pathogen’s alarming multidrug resistance capabilities, underscoring the urgent need for robust antimicrobial stewardship programs and comprehensive research into its epidemiological behavior and resistance mechanisms. Incorporating rare pathogens into differential diagnoses, particularly for elderly patients with recurrent UTIs, could improve patient outcomes significantly. Finally, these findings expand the limited existing data on Cedecea lapagei infections, providing valuable insights into more precise diagnostic methodologies and tailored therapeutic approaches.
Aspergillus fumigatus endocarditis in an immunocompetent host aided by metagenomic next-generation sequencing assay: case report and literature review
Plazola Carlos E.,
Rehman Aliya,
Morel Maria,
Vu Christine,
Castro Jose G.,
Ayoade Folusakin
Aspergillus fumigatus endocarditis is a rare but severe infection associated with high mortality, typically affecting immunocompromised individuals. Diagnosing fungal endocarditis can be challenging due to the often negative blood cultures and nonspecific symptoms. We present a case of Aspergillus fumigatus infective endocarditis in a 59-year-old immunocompetent man with no typical risk factors, diagnosed with the assistance of metagenomic microbial plasma cell-free DNA next-generation sequencing assay (Karius test). The patient presented with ocular symptoms and was found to have a heart murmur and a hypodense liver lesion, leading to suspicion of infective endocarditis. Blood cultures failed to reveal a pathogen, but elevated fungal biomarkers and the Karius test supported Aspergillus fumigatus as the causal agent. The patient received antifungal therapy with voriconazole and liposomal amphotericin B followed by surgical intervention for mitral valve replacement. The case exemplifies the difficulty in diagnosing Aspergillus endocarditis, as blood cultures are often negative and histological confirmation may be delayed. Molecular diagnostics, such as metagenomic microbial plasma cell-free DNA next-generation sequencing assay, significantly enhance pathogen detection in culture-negative cases, however, although treatment with antifungal therapy and surgery can improve outcomes, the high mortality associated with Aspergillus endocarditis remains a critical concern, highlighting the need for further research and advancements in both diagnostic and therapeutic approaches.
Strongyloides stercoralis hyperinfection with shock and thrombosis
López-Delgado Darío Sebastián,
Narváez Carlos A.,
Bonfante-Villalobos Roberto,
Arteaga Joshua Emmanuel,
Sanchez-Galvez Hector Fabio,
Jurado Yamile,
Rodriguez-Morales Alfonso J.
Strongyloides stercoralis (SS) is an intestinal parasite that can cause chronic asymptomatic infections, but in rare cases, it can progress to hyperinfection syndrome (SHS). This report describes a case of SHS associated with deep vein thrombosis and pulmonary thromboembolism, a rare manifestation in an immunocompetent patient. A 19-year-old female patient with a 15-day history of abdominal pain, progressive edema of the lower limbs, hemoptotic cough, asthenia, and weight loss. During her hospitalization, she developed sudden dyspnea, desaturation, and distributive shock, requiring invasive mechanical ventilation. Pulmonary angiotomography showed pulmonary thromboembolism, and deep vein thrombosis was diagnosed. Bronchoscopy revealed alveolar hemorrhage, while bronchoalveolar and duodenal lavage confirmed the presence of SS. Ivermectin and albendazole were started with full-dose anticoagulation for the thrombotic event. After one week of management, bronchoalveolar lavage results were negative, and the patient showed significant improvement with no long-term complications. SHS is rare in immunocompetent patients, and its association with thrombosis has been poorly documented in the literature. This case emphasizes the importance of early diagnosis and timely management to avoid life-threatening complications. It also highlights the need for surveillance in endemic regions and the appropriate use of evidence-based therapeutic strategies.
The Infections in the History of Medicine
Eat and heal. Past, present and future of maggot debridement therapy: a narrative review
Simonetti Omar,
Zerbato Verena,
Bellinato Francesco,
Cavalli Fabio,
Armocida Emanuele,
Luzzati Roberto,
Di Bella Stefano,
In medicine, fly larvae play a dual role: they can be both harmful causative agents of diseases and therapeutic agents. In fact maggot debridement therapy (biosurgery) is the controlled use of larvae to treat infected wounds and dates back to the beginnings of medicine. Ambroise Paré and Dominique-Jean Larrey pioneered the field of biosurgery before the 18th century, but it was John Forney Zacharias during the American Civil War who officially documented and promoted this medical application. The success of this method was immediate. Nevertheless, germ theory and the postulates of Robert Koch discouraged physicians from using potentially contaminated material such as larvae from the second half of the 19th century onwards. In the first half of the 20th century, however, the practice regained momentum thanks to the sterilization of fly eggs and the success of Dr. Stanton K. Livingston in the treatment of chronic osteomyelitis with biotherapy. The use of larvae for therapeutic purposes was discontinued after the Second World War due to the discovery of penicillin and is now receiving some attention again due to the emergence of antibiotic-resistant bacteria. Although biosurgery is rarely encouraged, the results of systematic reviews and meta-analyzes support its use. Previous and current evidence shows that this practice may be as useful as ever in the age of antibiotic resistance. It is likely that larval therapy will be considered as a stand-alone tool in the near future.
Letters to the editor
Detection of Chlamydia trachomatis, Neisseria gonorrhoeae and Ureaplasma urealyticum in symptomatic and asymptomatic subjects
Ciccarese Giulia,
Pattaro Matilde,
Salvi Ilaria,
Salvia Giorgia,
Fidanzi Cristian,
Herzum Astrid,
Varesano Serena,
Broccolo Francesco,
Drago Francesco
Not available
