Volume 34, Issue 2, 2026
Editorial
When Faster Diagnosis Is Not Enough: Bringing Diagnostic Stewardship into Antimicrobial Stewardship
Mezzadri Luca,
Bonfanti Paolo
Not available
Some considerations on hantavirus infections and Andes virus epidemic on the cruise ship Hondius
Galli Massimo,
Mussini Cristina,
SIMIT on Behalf of
Not available
Review
Imported Leishmaniasis in Europe (2000–2024): A systematic review of travel-related case reports
Alcocer-Veintimilla Sandra M.,
Pillajo-Gangotena Víctor A.,
Acosta-España Jaime David,
Abbara Aula,
González-Sanz Marta,
Rodriguez-Morales Alfonso J.
Background: This review aims to systematically analyze imported leishmaniasis cases reported between 2000 and 2024, focusing on geographic origin, host demographics, clinical manifestations, diagnostic approaches, and species distribution.
Methods: A systematic review was conducted in accordance with the PRISMA guidelines across PubMed, Scopus, and Web of Science. Inclusion criteria encompassed case reports and series in English or Spanish that described laboratory-confirmed human leishmaniasis acquired outside of Europe. The risk of bias was assessed using the JBI Critical Appraisal Tool. Data was extracted and analyzed using RStudio (v4.3.1) for statistical exploration, including subgroup analysis and temporal trends. The protocol was registered in PROSPERO (CRD420251128116).
Results: Twelve studies documenting 127 published cases were reviewed, mainly from Germany, Spain, Poland, and Austria. The most common form was cutaneous leishmaniasis (63%), followed by mucocutaneous (27%) and visceral (10%). Visceral leishmaniasis was significantly linked to lower odds of being a tourist (OR: 0.24; 95% CI: 0.07–0.87; p = 0.027). Diagnostic methods varied, including PCR, histology, and microscopy. The main species were L. braziliensis, L. panamensis, and L. donovani. Treatments involved liposomal amphotericin B and systemic antimonials, though resistance and outcomes were inconsistently reported.
Conclusions: The importation of leishmaniasis in Europe highlights a growing health challenge. Diagnostic variability, underreporting, and limited clinician awareness cause delays and mismanagement. Enhancing surveillance, standardizing diagnostics, and adding pre-travel advice to routine care are vital. Future research should focus on species resistance, coinfections, and long-term effects for better guidelines.
HIV-2 infection in Europe – persistence by migrant flows from West Africa
but low spillover into the native population
Soriano Vicente,
Nieto María del Carmen,
Lozano Ana Belén,
Pena MaríaJosé,
Ramos José Manuel,
Algarate Sonia,
Rando Ariadna,
Moreno-Torres Víctor,
Barreiro Pablo,
de Mendoza Carmen,
HIV-2 was isolated in 1986 in AIDS patients with negative or indeterminate HIV-1 antibodies. Most HIV-2 patients initially reported were West African migrants living in Europe. Independence wars during the 1960s for French colonies and, in the 1970s, for Portuguese colonies, fueled population exchanges, including military personnel. The Ivory Coast and Guinea-Bissau acted as the respective epicenters of HIV-2 spillover into France and Portugal.
Other European countries (i.e., Belgium, the Netherlands, Spain, Italy, Germany, etc.) reported HIV-2 cases in the late 1980s. Although the majority were migrants from West Africa, there were also natives who had traveled to or had sex partners from there. By 1990, nearly 500 cases of HIV-2 infection had been confirmed in Europe. By 2010, nearly 2,000 cases had been reported only in Portugal.
National surveillance data across Europe remain scarce, hindering precise and up-to-date estimates of HIV-2 infection. Spain is a notable exception, as it has maintained a register since 1989, with 428 HIV-2 cases reported by the end of 2025. Current consensus indicates that new HIV-2 infections are declining across Europe. Migrants from West Africa continue to be the largest contributors, with no evidence of significant HIV-2 spread into the native European population. This ongoing pattern underscores both the importance of surveillance and the limited transmission of HIV-2 beyond migrant communities.
The multifaceted antiretroviral coverage provided by BIC/FTC/TAF: a pharmacokinetic/pharmacodynamic revisitation
Di Perri Giovanni,
Calcagno Andrea
The treatment of HIV infection has entered a dichotomic phase, as conventional triple oral regimens are now sharing the landscape with oral and injectable dual combinations. By looking at the new antiretrovirals in the pipeline it is apparent that the future of HIV treatment will be largely covered by potent long-acting dual regimens, with an increasing shift toward injectable formulations allowing much less frequent administration. However, the current HIV-infected population still includes a large proportion of patients with a variety of immunovirological conditions whose weaknesses require the currently available strongest option, such as a triple oral regimen including a 2nd generation integrase strand-transfer inhibitor (INSTI) like the co-formulation containing Bictegravir (BIC), Emtricitabine (FTC) and Tenofovir alafenamide (TAF). Further to a proportion of newly diagnosed HIV infections at an advanced disease stage still exceeding 50%, many are the patients whose history may include a late start of treatment, virologic failures and a suboptimal immune recovery. BIC/FTC/TAF is the point of arrival of decades of antiretroviral research and has the pharmacologic characteristics to guarantee the therapeutic success in most patients with difficult-to treat infections. Properties like intrinsic potency, strong genetic barrier and forgiveness of BIC/FTC/TAF are unique among currently available antiretroviral regimens and make this single tablet combination as the gold standard for comparative studies of new therapeutic solutions. The main clinical-pharmacologic features of BIC/FTC/TAF are here analysed with the intention to focus on some key advantages this regimen may offer whenever the individual conditions are less than ideal for a dual regimen.
Nipah virus infection: what clinicians need to know
Gupta Nitin,
Das Adhikari Shreya,
Gupta Mukund,
Singh Sonali,
Kumar Tirlangi Praveen,
Rodriguez-Morales AlfonsoJ.,
Boodman Carl
Nipah virus infection is an uncommon but highly lethal zoonotic illness that primarily presents with acute encephalitis and respiratory disease in humans. After its initial identification during the Malaysia–Singapore outbreak of 1998–1999, human outbreaks have since been reported in Bangladesh and India. Despite the relatively small number of reported cases, the Nipah virus remains a major clinical and public health concern because of its high mortality, capacity for person-to-person transmission, lack of approved antiviral treatment, and potential for amplification within healthcare settings. For clinicians, the major challenge lies in early recognition of a disease that initially presents with nonspecific febrile symptoms but may rapidly progress to severe encephalitis, acute respiratory distress syndrome, or both. Human-to-human transmission has been well documented in South Asian outbreaks, particularly in household and healthcare settings, underscoring the importance of prompt isolation and infection prevention measures. Laboratory confirmation relies primarily on reverse transcription polymerase chain reaction, with serology providing supportive evidence later in the course of illness. Management remains largely supportive, with intensive care often required in severe cases. This review provides a practical clinician-oriented overview of Nipah virus infection, focusing on epidemiology relevant to frontline practice, clinical presentation, transmission, diagnostic approach, infection control, treatment, prognosis, and outbreak response.
Sexually Transmitted Infections in adolescents and young adults: a growing public health challenge
Pipitò Luca,
D’Agati Giulio,
Cascio Antonio
Background: Sexually transmitted infections (STIs) represent a major global public health challenge, particularly among adolescents and young adults aged 15–24 years, who account for a disproportionate share of incident infections worldwide.
Methods: We conducted a narrative review of the literature, synthesizing recent epidemiological data, risk factors, and prevention strategies related to STIs in adolescents and young adults. Relevant articles were identified through major scientific databases and international surveillance reports.
Results: This narrative review summarizes current epidemiological trends, risk factors, and prevention strategies related to STIs in young populations. The global burden of both bacterial infections, such as Chlamydia trachomatis, Neisseria gonorrhoeae, and Treponema pallidum, and viral infections, including HIV, human papillomavirus, and herpes simplex virus, remains high in this age group. Adolescents and young adults are particularly vulnerable due to a complex interaction of biological susceptibility, behavioral factors, and structural determinants such as limited access to sexual health services, stigma, and inadequate sexual health education. Specific subpopulations, including men who have sex with men, transgender youth, and young sex workers, experience markedly higher STI prevalence and incidence. A key challenge in STI control among young people is the high prevalence of asymptomatic infections, which substantially limits syndromic management and underscores the importance of systematic screening strategies. Evidence-based prevention approaches include vaccination, HIV pre-exposure prophylaxis, behavioral interventions, expanded screening programs, and youth-friendly healthcare services. Addressing the STI burden in young populations requires integrated public health strategies that combine biomedical interventions with efforts to reduce social and structural inequities influencing sexual health outcomes.
Conclusions: Reducing the burden of STIs in adolescents and young adults requires integrated, multi-level strategies combining prevention, early diagnosis, and equitable access to youth-friendly healthcare services, alongside targeted interventions addressing the specific needs of high-risk populations.
Insights into parvovirus B19 clinical and virological dynamics among blood donors
La Raja Massimo,
Benvenuto Nicola,
Marconi Monica,
Costantino Venera,
Belgrano Anna,
Di Bella Stefano
Coinciding with the exceptional European resurgence of human parvovirus B19 (B19V), between 2023 and 2024, twelve B19V DNA-positive blood donations out of 27.737 were detected by the plasma fractionating industry via nucleic acid testing (NAT) and notified to the blood collection centers of Trieste and Gorizia (Italy).
In order to prevent potential B19V transmission, the implicated donors were recalled for clinical and virological follow-up for one year. None of the subjects had reported symptoms at the time of donation, though six subjects subsequently recalled either mild, transient symptoms in the days following donation or household exposure to fifth disease.
The range of index viral loads ranged from 6.6×103 to >1.0×103 IU/mL, with the majority of donations exceeding 103 IU/mL. The viral burden exhibited a rapid decline, dropping below 103 IU/mL after approximately four months and subsequently falling below 5×10³ IU/mL in all the monitored donors by eight months, although low-level viremia persisted. IgG antibodies were detected in all subsequent samples, while IgM persisted for up to 125 days in the majority of donors and remained detectable in three cases, including one instance lasting up to 355 days.
Since transfusion-transmitted B19V infection has been documented at viral loads as low as 5 × 10³ IU/mL, our data suggest that a theoretical risk of transmission may persist for up to nine months. Nevertheless, based on hemovigilance, transfusion-transmitted B19V infection appears to have limited clinical impact, likely due to the high level of population immunity and the predominance of non-infectious viral DNA during the late phase of infection. Overall, these observations support current policies that do not mandate routine B19V screening, while underscoring the importance of targeted testing in high-risk recipients and the temporary deferral of highly viraemic donors for 4–6 months.
Original article
Effectiveness and Safety Profile of BIC/TAF/FTC in People living with HIV Switched from Other Antiretroviral Regimens: A Real-Life Retrospective Cohort Analysis
Pipitone Giuseppe,
Marrali Domenico,
Goad Marilee,
Giordano Myriam,
Abbott Michelle,
Gizzi Andrea,
Sanfilippo Adriana,
Guida Marascia Federica,
Agrenzano Stefano,
Imburgia Claudia,
Cascio Antonio,
Iaria Chiara
Background: Switching antiretroviral therapy (ART) is a common strategy in people living with HIV (PLWH) to improve tolerability, to manage comorbidities, and to optimize long-term safety. Bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) is a single-tablet regimen with proven effectiveness in clinical trials. Real-world data continue to confirm its effectiveness across diverse clinical settings.
Methods: We conducted a retrospective observational cohort study including PLWH who switched to BIC/TAF/FTC from other ART regimens in routine clinical practice. At both baseline and during follow-up, we collected demographic characteristics, comorbidities, virological and immunological markers, and laboratory safety parameters.
Results: The study included 177 PLWH, with a median age of 55 years (IQR 44.4–60.3). 70.6% were male and 68.9% were aged ≥50 years. The median follow-up was 38.7 months (IQR 26.9–52.2). At baseline, 93.2% (165/177) of participants had suppressed HIV-RNA (<50 copies/mL). After switching to BIC/TAF/FTC, virological suppression (HIV-RNA <50 copies/mL) improved to 98.3% (174/177) at follow-up (p=0.007). Three participants had HIV-RNA ≥50 copies/mL at follow-up; none showed confirmed virological failure and no new resistance mutations were identified. Median CD4+ T-cell count showed a non-statistically significant trend toward increase from 562 (IQR 373–774) to 596 cells/µL (IQR 396–753) (p=0.057), while the CD4/CD8 ratio increased from 0.90 (IQR 0.60–1.30) to 0.94 (IQR 0.65–1.51) (p<0.001). A statistically significant decrease in total cholesterol (189 vs 180 mg/dL, p=0.013) was also observed. No clinically significant changes were observed in renal, hepatic, or hematological parameters.
Conclusions: In this real-life cohort, switching to BIC/TAF/FTC was associated with an improvement in virological suppression, an increase in CD4/CD8 ratio, and a favorable safety and metabolic profile, supporting its use as an effective and well-tolerated switch option in routine clinical practice.
Epidemiology of imported malaria in an area of North-Eastern Italy (2016-2025): clinical focus on cerebral malaria
Corich Lucia,
Bortolin Maria Teresa,
Tedeschi Rosamaria,
Casarotto Mariateresa,
Pancino Antonella,
Molaro Alberto,
Anzanello Valentina,
Basaglia Giancarlo,
Corich Maria Ada
Background: In non-endemic settings, imported malaria poses diagnostic challenges due to non-specific presentations and lack of immunity, especially in visiting friends and relatives (VFRs). Focusing on the Western Friuli (Italy) observatory, this work aims to optimize triage by identifying early severity predictors. Through the analysis of clinical parameters, paediatric cerebral cases, and host genetics - including an illustrative case of HbS/β-thalassaemia - we evaluate the drivers of Plasmodium falciparum progression to improve patient management.
Methods: This retrospective study (2016–2025) analysed symptomatic malaria cases in the Friuli Occidentale Health Authority, combining epidemiological data with illustrative clinical cases. Diagnosis was confirmed via microscopy and molecular methods. Using WHO/AMCLI criteria, we evaluated admission parameters, including procalcitonin (PCT), C-reactive protein (CRP), and platelet count, to identify predictors of severe malaria, adopting a ≥2% parasitaemia threshold. Diagnostic accuracy was assessed via multivariable logistic regression and ROC analysis.
Results: Of the 124 malaria cases (P. falciparum 88.71%), 90.32% were VFRs, primarily from West Africa; only 12% reported adequate prophylaxis. Severe malaria occurred in 19.35% (24/124), including two cerebral malaria (CM) cases, with no fatalities. Severity fluctuated significantly, peaking at 60% (6/10; 95% CI: 26.2%–87.8%) in 2025. Multivariable analysis identified parasitaemia ≥2% (aOR 8.44; 95% CI 2.41–29.58; p= 0.001) and PCT (aOR 1.23; 95% CI 1.06–1.42; p= 0.007) as the only independent severity predictors. PCT outperformed CRP (AUC 0.84 vs 0.73); at a 5.10 ng/mL cut-off, PCT demonstrated a 95.9% negative predictive value (NPV), effectively identifying low-risk patients. CM Case 1 (2017): A 5-year-old male with HbS/β-thalassaemia (VFR, from Ghana) admitted for P. falciparum malaria (9.5% parasitaemia) and severe anaemia, evolving into CM (loss of consciousness, seizures, BCS score 0); successfully treated with IV artesunate, antiepileptics, and blood transfusions, without sequelae. CM Case 2 (2022): A 3-year-old male (VFR, from Burkina Faso) with P. falciparum malaria (12.6% parasitaemia) evolving into CM (altered state of consciousness, EEG signs of cerebral distress, retinal haemorrhage, BCS score 2); resolved with IV artesunate and antiepileptics without sequelae.
Conclusions: Imported malaria remains a critical challenge due to unpredictable severity trends and non-specific onset of CM. PCT, combined with parasitaemia, outperformed CRP and platelet count as an independent predictor of severity. High PCT levels should serve as a "red flag" for immediate triage and parenteral therapy. Integrating PCT into clinical guidelines is essential for effective risk stratification and preventing life-threatening complications in non-endemic settings.
Rezafungin and catheter-related candidemia: a new player in a high-stakes game
Venturini Sergio,
Reffo Ingrid,
Zanus-Fortes Agnese,
del Fabro Giovanni,
Callegari Astrid,
Giovagnorio Federico,
Negri Camilla,
Casarotto Mariateresa,
Basaglia Giancarlo,
Zanusso Chiara,
Basso Barbara
Candidemia remains a significant healthcare-associated infection characterized by high mortality rates and considerable resource utilization. While echinocandins are established as first-line treatment, extended daily intravenous administration often delays patient discharge, particularly when transitioning to oral azoles is not feasible. Rezafungin, a novel long-acting echinocandin, offers once-weekly dosing with predictable pharmacokinetics.
This prospective observational pilot study examined consecutive cases of guideline-defined catheter-related candidemia (CRC) diagnosed in medical wards at two Italian hospitals in 2025. All subjects initially received short-acting echinocandin therapy alongside catheter removal for source control. Upon meeting predefined clinical and microbiological stability criteria, patients were administered a single dose of rezafungin on day 7. Primary outcomes included clinical success and microbiological clearance at 30 days. Secondary endpoints encompassed reductions in hospital length of stay, relapse rates, mortality, and adverse drug events.
Seven patients received rezafungin as consolidation therapy. The cohort was characterized by advanced age and a high comorbidity burden. Microbiological eradication was achieved in all cases. No adverse events related to the drug, nor relapses or mortalities, were observed at 30- and 90-day follow-up. The median estimated decrease in hospital stay was four days, translating to 28 bed-days saved.
This real-world pilot cohort demonstrated that a stepwise antifungal strategy incorporating rezafungin following initial echinocandin therapy is feasible, well-tolerated, and associated with favourable short-term outcomes. Such an approach may facilitate earlier patient discharge, mitigate vascular-access issues, and support more efficient management of catheter-related candidemia. Larger, multicenter controlled studies are necessary to verify the clinical, economic, and sustainability benefits.
Case report
Refractory XDR Klebsiella pneumoniae CAUTI Treated with non-antibiotic urinary acidification: a 12-month follow-up case report and literature review
Job Merin Anna,
Kandachamkulam Manu Dius,
Fernandes Dani Dius
Background: The increase of catheter-associated urinary tract infections (CAUTIs) caused by extensively drug-resistant (XDR) Klebsiella pneumoniae represents a critical failure of the current antimicrobial paradigm. In geriatric cohorts with significant comorbidities, the exhaustion of conventional therapeutic options often precipitates a cycle of recurrent sepsis, prolonged hospitalization, and prohibitively high healthcare expenditure. When "last-resort" agents such as ceftazidime-avibactam and colistin fail, clinicians in resource-limited settings are left with no guideline-endorsed alternatives. This report evaluates the clinical and economic impact of a pragmatic non-antibiotic acidification strategy applied as a salvage intervention in a "pan-resistant" scenario.
Case Report: We describe the complex clinical course of an 82-year-old female with type 2 diabetes and neurogenic bladder following an acute ischemic stroke. Despite rigorous adherence to standard catheter care protocols, she developed intractable, recurrent XDR K. pneumoniae CAUTI. The pathogen demonstrated resistance to all first-line and reserve antibiotics, leading to four ICU admissions within a single trimester. With methenamine hippurate unavailable and the family declining suprapubic diversion, we initiated a physiological acidification protocol. This regimen synergized high-dose oral ascorbic acid (2g/day) - hypothesized to downregulate virulence genes - with twice-daily bladder irrigation using diluted (0.25%) acetic acid to create a hostile pH environment for bacterial adherence.
Literature Search Methods and Results: Utilizing PRISMA principles adapted for narrative synthesis, a systematic search of PubMed and Scopus yielded 145 initial results. After screening for relevance to non-antibiotic salvage therapy and biofilm disruption, 17 highly relevant articles were incorporated to validate the mechanistic plausibility of our combined protocol.
Conclusions: Following initiation of the intervention, a sustained absence of symptomatic episodes was observed. Over a 12-month follow-up, the patient remained free of CAUTI, requiring no further antibiotic therapy. We posit that low-cost, accessible acidification adjuncts represent a vital "frugal innovation" for antimicrobial stewardship in vulnerable populations.
Rhizobium radiobacter bloodstream infection associated with long-term central venous access in an infant with Pompe disease
Cuccia Alessandra,
Albano Chiara,
Garbo Valeria,
Venuti Laura,
Boncori Giovanni,
Linares Giulia,
Saporito Laura,
Falletta Federico,
Colomba Claudia,
Rhizobium radiobacter (formerly Agrobacterium tumefaciens) is an environmental Gram-negative bacillus increasingly recognized as an opportunistic human pathogen, particularly in association with indwelling medical devices. Bloodstream infections (BSI) caused by this organism are rarely reported in children.
We describe a 10-month-old girl with infantile-onset Pompe disease undergoing weekly enzyme replacement therapy (ERT) via central venous catheter who presented with fever and clinical deterioration 72 hours after infusion. Initial inflammatory markers were not significantly elevated, and multiplex molecular assays were negative for bacterial pathogens. Blood culture obtained from the catheter became positive after 25 hours, yielding Gram-negative bacilli subsequently identified as R. radiobacter. The isolate showed susceptibility to aminoglycosides, carbapenems, and fluoroquinolones, with intermediate susceptibility to piperacillin/tazobactam.
Targeted antimicrobial therapy led to rapid clinical improvement and clearance of bacteremia without catheter removal.
This case highlights both the pathogenic potential of uncommon environmental microorganisms in fragile children with long-term intravascular devices and the continuing diagnostic value of conventional blood cultures, particularly when rapid molecular assays are negative.
Our experience also supports the possibility of catheter salvage in clinically stable patients responsive to appropriate antimicrobial therapy.
The Infections in the History of Medicine
Asian Flu in Milan, 1957. A brief history of the first pandemic occurred after the discovery of Influenza A virus and its impact in a large Italian city
Galli Massimo,
Adorni Fulvio
Asian flu emerged in southern China in the last months of 1956 and after reaching Singapore and Hong spread in the rest of the world. Phylogenetic studies subsequently revealed that the new virus, called H2N2, was the product of a reassortment of a H1N1 strain circulating in humans with an avian strain that contributed polymerase subunit 1 (PB1), hemagglutinin and neuraminidase coding genes. The peak of the epidemic in most European countries occurred in autumn 1957. Compared to the Spanish flu, mortality was significantly lower, with an estimated number of two million deaths and case-fatality rate below 0.2%. Excess mortality rates varied across countries, with the lowest observed in Europe and the highest in Latin America. Compared to previous years, mortality rate increased during pandemic in school-age children and young adults more than in the other age groups. In Italy, the cases peaked in October 1957 and it has been suggested that their actual number exceeded 8 million, i.e. one-sixth of the total Italian population at the time. However, from 1950 to 1957 no significant variation was observed either in the total number of deaths or in the annual death rates and the deaths occurred in 1957 were even fewer than in previous year. In Milan - the second largest city in Italy - over the three-year period from 1956 to 1958 an increase of just over 300 deaths was observed in 1957, compared with the approximately 140 expected. Deaths directly attributed to influenza were 178 out of the 28,020 deaths observed in the three-year period (6.3‰). Although Asian flu affected mostly young people and children worldwide, the majority of deaths attributed to influenza in Milan occurred among individuals over 55 years of age, predominantly males. Despite the large number of infections and deaths it caused, the impact of the new pandemic on mortality and global population growth has been limited and not comparable to with that of the 1918 pandemic. Nevertheless, Asian flu exerted a strong influence on healthcare organization worldwide. The new pandemic gave a strong final push towards overcoming the fragmentation of competences on health among different ministries with the establishment of the Ministry of Health in Italy.
Letters to the editor
Fragility of Immunisation and Water Systems in Gaza: Infectious Disease Risks in a Conflict-Affected Setting
Scotto Angelo,
Fazio Vincenzina,
Scotto Gaetano
Not available
Re-Evaluating global measles management: lessons from the 2026 Bangladesh outbreak
Rahman Mamunur
Not available
