Luca Masucci

Malaria remains a major global health threat, particularly in endemic regions of sub-Saharan Africa. In 2024 alone, an estimated 282 million cases were reported worldwide, with approximately 610,000 associated deaths. Beyond the high disease burden, mixed-species Plasmodium infections represent an additional clinical challenge, as they are frequently underdiagnosed and may significantly complicate both diagnostic accuracy and therapeutic management even in non-endemic countries. We report the case of a 67-year-old man from Guinea who presented to the Emergency Department with high-grade fever and asthenia shortly after returning to Italy; initial microbiological investigations were negative, despite markedly elevated inflammatory markers were diagnosed. The patient reported a previous untreated malaria episode approximately six months earlier, raising suspicion of a novel Plasmodium infection. A comprehensive malaria diagnostic workflow was promptly initiated, integrating rapid immunoenzymatic testing (IE), microscopy, and molecular assays. The IE test suggested Plasmodium falciparum or a mixed infection as result, while loop-mediated isothermal amplification (LAMP-PCR) confirmed the presence of Plasmodium spp DNA. Microscopic examination of stained blood smears revealed typical P. falciparum ring forms and suspected P. ovale trophozoites; so, species-specific real-time PCR confirmed a mixed infection with P. falciparum and P. ovale , supporting prompt antimalarial treatment. Final molecular confirmation was achieved by Sanger sequencing, which identified the Plasmodium ovalecurtisi as co-aetiological agent of disease. The rapid and integrated diagnostic approach enabled timely initiation of appropriate antimalarial therapy with artemether–lumefantrine and primaquine, leading to complete clinical recovery and gene sequencing allowed a correct species confirmation and epidemiological characterization. This case highlights the importance of combining microscopic analysis with advanced molecular diagnosis for an accurate identification of mixed Plasmodium infections even in country and contributes novel epidemiological data through molecular characterization of P. ovalecurtisi in an imported case.

Vector‐Borne Diseases (VBDs), transmitted by arthropods such as mosquitoes, ticks, fleas and sandflies, represent a significant threat to global health. These diseases can be caused by a variety of pathogens, including bacteria, viruses, protozoa, and helminths. This article explores classification and biological characteristics of vectors with a particular emphasis on their role in disease transmission. It also discusses the key genetic, environmental and socioeconomic factors that influence vector competence and vectorial capacity. The review focuses on the epidemiology, transmission mechanisms and clinical manifestations of major VBDs, including West Nile virus, Dengue, Leishmaniasis, Lyme disease and Malaria. In addition, it examines current diagnostic methodologies, vector surveillance strategies and molecular approaches for disease monitoring. Preventive and control strategies—such as integrated vector management, biological control and vaccination programs and innovative interventions—are also evaluated. A comprehensive understanding of the complex interactions among vectors, pathogens and hosts, together with advancements in detection and intervention technologies, is essential for the development of effective public health strategies.

Background: Untargeted microbiome modulation has achieved conflicting results in post-infectious irritable bowel syndrome (PI-IBS). Methods: In a case–control study of PI-IBS patients, cases received targeted microbial modulation informed by microbiome profiling, while controls were managed by standard therapy. Treatment response was defined as a decrease in IBS-symptom severity scale (IBS-SSS) ≥50 points. Results: All thirteen cases (100%) and 11/20 controls (55%) experienced treatment response (p < 0.0001). The mean IBS-SSS score after treatments was 163 in cases and 231 in controls (p = 0.01). Conclusions: Based on our preliminary results, therapeutic microbiome modulation might be a promising strategy for PI-IBS. Further studies are needed to clarify its role.

Renal cell carcinoma (RCC) is a common malignancy with limited durable responses to first-line immune checkpoint inhibitor (ICI)-based therapies. Emerging evidence implicates the gut microbiome in modulating ICI efficacy. In the investigator-initiated, randomized, double-blind placebo-controlled phase 2a TACITO trial, we evaluated whether fecal microbiota transplantation (FMT) from complete ICI responders enhances clinical outcomes in treatment-naive patients with metastatic RCC (mRCC) receiving pembrolizumab + axitinib. The primary endpoint was the rate of patients free from disease progression at 12 months after randomization (12-month progression-free survival (PFS)). Secondary endpoints were median PFS and median overall survival, objective response rate (ORR), safety and microbiome changes, after randomization. Forty-five patients randomly received donor FMT (d-FMT) or placebo FMT (p-FMT). Although the primary endpoint was not met (70% versus 41% for d-FMT versus p-FMT, respectively, P = 0.053), the secondary endpoint of median PFS was significantly longer with d-FMT (24.0 months in the d-FMT arm versus 9.0 months in the p-FMT arm; hazard ratio = 0.50, P = 0.035). The ORR was 52% of patients in the d-FMT arm and 32% of patients receiving placebo. Microbiome analysis confirmed donor strain engraftment and increased α-diversity and larger microbiome shifts (β-diversity) compared with baseline composition in the d-FMT treatment group. Acquisition or loss of specific strains, but not total engraftment, was associated with the primary endpoint. Our findings support the safety and potential efficacy of selected donor FMT to enhance ICI-based treatment in mRCC, which deserves further investigations. ClinicalTrials.gov identifier: NCT04758507.

Multiple Sclerosis (MS) has long been recognized as a multifactorial disease, associated with both genetic and enviromental factors. Its link to inflammatory processes has led to significant advances in understanding the immunological and neurobiological mechanisms underlying the disease. The presumed autoimmune etiology is currently guiding the development of therapeutic protocols in this direction. The intestinal bacteria population, known as Gut Microbiota (GM), plays a well-documented role in autoimmune and inflammatory diseases. Gut microbiota dysbiosis is associated in patients affected by MS. Fecal Microbiota Transplantation (FMT) is emerging as a potential strategy to restore eubiosis and modulate systemic inflammation. We treated a 42-year-old woman with severe MS disability by FMT via colonoscopic infusion followed by a 3-month treatment of daily oral capsules, containing frozen microbiota, in order to resolve gastrointestinal symptoms. Clinical follow-up was conducted at 30, 60, and 90 days. Microbiota profiling (16S rRNA sequencing) and intestinal permeability testing were performed at several time points before and post infusion. Post-FMT, gastrointestinal symptoms improved significantly, as well as in limb spasticity, trunk stability, and fine motor skills. Microbiota analysis revealed a marked reduction in the abundance of Akkermansia muciniphila (22.5% vs 6.6%). At phylum level, Actinomycetota remained elevated (22%), while Bacteroidota consistently showed low abundance (14%). The most favorable microbiota profile was observed at 90 days, which coincided with the peak of clinical improvement. Intestinal permeability also improved over time, despite the patient’s microbiota profile remaining distinct from the donor. This is the first report about combined FMT in MS. The procedure was safe, well tolerated, and associated with both gastrointestinal and neurological improvements. These findings support further exploration of FMT as a therapeutic adjunct in MS through controlled clinical trials.

The bilateral interaction between the brain and the gut has recently been on the spectrum of researchers’ interests, including complex neural, endocrinological, and immunological signaling pathways. The first case reports and clinical studies have already reported that delivering microbes through fecal microbial transplantation (FMT) may alleviate symptoms of psychiatric disorders. Therefore, modifying the gut microbiota through FMT holds promise as a potential treatment for psychiatric diseases. This scoping review assessed studies from PubMed related to FMT in autism spectrum disorder and attention deficit hyperactivity disorder. The evaluation included nine clinical studies and case reports. The beneficial and persistent effect on the autism spectrum disorder (ASD) symptoms has been reported. Also, an increased microflora diversity and altered levels of neurometabolites in serum were identified, albeit with a tendency to return to baseline over time. The microbiome–gut–brain axis could provide new targets for preventing and treating psychiatric disorders. However, a recent large randomized clinical trial has shed light on the previously collected data and suggested a possible contribution of the placebo effect. This highlights the necessity of large randomized double-blind studies to reliably assess the effect of FMT in ASD.

Background: Fecal microbiota transplantation (FMT) is emerging as a potential treatment modality for individuals living with inflammatory bowel disease (IBD). Despite its promise, the effectiveness of FMT for treating IBD, particularly for ulcerative colitis (UC), still requires thorough clinical investigation. Notwithstanding differences in methodologies, current studies demonstrate its potential for inducing remission in UC patients. Therefore, standardized and robust randomized clinical trials (RCTs) are needed to further support its efficacy for managing UC. The aim of the second Rome Consensus Conference was to address gaps and uncertainties identified in previous research regarding FMT and to offer a robust framework for future studies applied to the treatment of UC. Methods: Global experts in the field of clinical IBD, mucosal immunology, and microbiology (N = 48) gathered to address the need for standardized clinical trials in FMT investigation. The group focused on key issues, such as stool donation, donor selection, characterization of fecal biomass, potential administration routes, as well as the process of induction, maintenance, and endpoint readouts. Results and Conclusions: The consensus achieved during this conference established standardization of methods and protocols to enhance the current quality of research, with the aim of eventual implementation of FMT in managing UC and the ultimate goal of improving patient outcomes.

A diverse and well-functioning gut microbiota normally serves as a protective shield against the invasion of harmful bacteria or the proliferation of opportunistic pathogens. Clostridioides difficile infection (CDI) is predominantly associated with the overuse of antibiotics, resulting in a significant alteration in the gut’s microbial balance. Unfortunately, the lack of global standardization does not allow for the identification of a set of biomarkers associated with the onset and progression of this disease. In this study, we examined the composition of the gut microbiota in patients at the time of the initial detection of CDI compared to a control group of CDI-negative individuals, with a focus on identifying potential CDI biomarkers for diagnosis. While no significant differences in the alpha and beta diversity between CDI-negative and CDI-positive individuals were found, we found that certain genera (such as Clostridium XIVa and Clostridium XVIII) showed different abundance patterns in the two groups, indicating potential differences in gut microbiota balance. In conclusion, am enrichment in Clostridium XI and a decrease in Faecalibacterium emerged in the CDI-positive patients and following antibiotic treatment, indicating that changes in the Clostridium/Faecalibacterium ratio may be a promising biomarker that warrants further investigation for CDI diagnosis.