Showing papers by "Federico Gobbi published in 2022"

Circulating microRNA signatures associated with disease severity and outcome in COVID-19 patients

Abstract: Background SARS-CoV-2 induces a spectrum of clinical conditions ranging from asymptomatic infection to life threatening severe disease. Host microRNAs have been involved in the cytokine storm driven by SARS-CoV-2 infection and proposed as candidate biomarkers for COVID-19. Methods To discover signatures of circulating miRNAs associated with COVID-19, disease severity and mortality, small RNA-sequencing was performed on serum samples collected from 89 COVID-19 patients (34 severe, 29 moderate, 26 mild) at hospital admission and from 45 healthy controls (HC). To search for possible sources of miRNAs, investigation of differentially expressed (DE) miRNAs in relevant human cell types in vitro. Results COVID-19 patients showed upregulation of miRNAs associated with lung disease, vascular damage and inflammation and downregulation of miRNAs that inhibit pro-inflammatory cytokines and chemokines, angiogenesis, and stress response. Compared with mild/moderate disease, patients with severe COVID-19 had a miRNA signature indicating a profound impairment of innate and adaptive immune responses, inflammation, lung fibrosis and heart failure. A subset of the DE miRNAs predicted mortality. In particular, a combination of high serum miR-22-3p and miR-21-5p, which target antiviral response genes, and low miR-224-5p and miR-155-5p, targeting pro-inflammatory factors, discriminated severe from mild/moderate COVID-19 (AUROC 0.88, 95% CI 0.80-0.95, p<0.0001), while high leukocyte count and low levels of miR-1-3p, miR-23b-3p, miR-141-3p, miR-155-5p and miR-4433b-5p predicted mortality with high sensitivity and specificity (AUROC 0.95, 95% CI 0.89-1.00, p<0.0001). In vitro experiments showed that some of the DE miRNAs were modulated directly by SARS-CoV-2 infection in permissive lung epithelial cells. Conclusions We discovered circulating miRNAs associated with COVID-19 severity and mortality. The identified DE miRNAs provided clues on COVID-19 pathogenesis, highlighting signatures of impaired interferon and antiviral responses, inflammation, organ damage and cardiovascular failure as associated with severe disease and death.

Presumptive treatment or serological screening for schistosomiasis in migrants from Sub-Saharan Africa could save both lives and money for the Italian National Health System: results of an economic evaluation.

Abstract: BACKGROUND Schistosomiasis can lead to severe irreversible complications and death if left untreated. Italian and European guidelines recommend serological screening for this infection in migrants from Sub-Saharan Africa (SSA). However, studies on clinical and economic impact of this strategy in the Italian and European settings are lacking. This study aims to compare benefits and costs of different strategies to manage schistosomiasis in migrants from SSA to Italy. METHODS A decision tree and a Markov model were developed to assess the health and economic impacts of three interventions: a) passive diagnosis for symptomatic patients (current practice in Italy); b) serological screening of all migrants and treating those found positive; c) presumptive treatment for all migrants with praziquantel in a single dose. The time horizon of analysis was one year to determine the exact expenses, and 28 years to consider possible sequelae, in the Italian health-care perspective. Data input was derived from available literature; costs were taken from the price list of Careggi University Hospital, Florence, and from National Hospitals Records. RESULTS Assuming a population of 100 000 migrants with schistosomiasis prevalence of 21·2%, the presumptive treatment has a greater clinical impact with 86.3% of the affected being cured (75.2% in screening programme and 44.9% in a passive diagnosis strategy). In the first year, the presumptive treatment and the screening strategy compared with passive diagnosis prove cost-effective (299 and 595 cost/QALY respectively). In the 28-year horizon, the two strategies (screening and presumptive treatment) compared with passive diagnosis become dominant (less expensive with more QALYs) and cost-saving. CONCLUSION The results of the model suggest that presumptive treatment and screening strategies are more favourable than the current passive diagnosis in the public health management of schistosomiasis in SSA migrants, especially in a longer period analysis.

Rapid spread of a new West Nile virus lineage 1 associated with increased risk of neuroinvasive disease during a large outbreak in northern Italy, 2022: One Health analysis.

Abstract: BACKGROUND A new strain of WNV lineage 1 (WNV - 1) emerged in the Veneto Region, northern Italy, in 2021, eight years after the last outbreak of WNV - 1 in Italy. The virus, which co-circulates with WNV-2, has become endemic in the Region, where, in 2022, most human cases of neuroinvasive disease (WNND) reported in Europe have occurred. METHODS Comparative analysis of the epidemiology and clinical presentation of WNV-1 and WNV-2 infection in humans, as well as the temporal and geographic distribution of WNV-1 and WNV-2 among wild birds and Culex pipiens mosquitoes in Veneto, from May 16th to August 21st, 2022, to determine if the high number of WNND cases was associated with WNV-1. RESULTS As of August 21st, 2022, 222 human cases of WNV infection were confirmed by molecular testing, including 103 with fever (WNF) and 119 with WNND. WNV lineage was determined in 201 (90.5%) cases, comprising 138 WNV-1 and 63 WNV-2 infections. During the same period, 35 blood donors tested positive, including 30 in whom WNV lineage was determined (13 WNV-1 and 17 WNV-2). Comparative analysis of the distribution of WNV-1 and WNV-2 infections among WNND cases, WNF cases and WNV-positive blood donors showed that patients with WNND were more likely to have WNV-1 infection than blood donors (odds ratio 3.44; 95% CI 95% 1.54 to 8.24; p = 0.0043). As observed in humans, in wild birds WNV-1 had higher infectious rate (IR) and showed a more rapid expansion than WNV-2. At variance, the distribution of the two lineages was more even in mosquitoes, but with a trend of rapid increase of WNV-1 IR over WNV-2. CONCLUSIONS Comparative analysis of WNV-1 vs WNV-2 infection in humans, wild birds, and mosquitos showed a rapid expansion of WNV-1 and suggested that WNV-1 infected patients might have an increased risk to develop severe disease.

A large case series of travel-related Mansonella perstans (vector-borne filarial nematode): a TropNet study in Europe

Abstract: Abstract Background Infection with Mansonella perstans is a neglected filariasis, widely distributed in sub-Saharan Africa, characterized by an elusive clinical picture; treatment for mansonellosis is not standardized. This retrospective study aimed to describe the clinical features, treatment schemes and evolution, of a large cohort of imported cases of M. perstans infection seen in four European centres for tropical diseases. Methods Mansonella perstans infections, diagnosed by identification of blood microfilariae in migrants, expatriates and travellers, collected between 1994 and 2018, were retrospectively analysed. Data concerning demographics, clinical history and laboratory examinations at diagnosis and at follow-up time points were retrieved. Results A total of 392 patients were included in the study. Of the 281 patients for whom information on symptoms could be retrieved, 150 (53.4%) reported symptoms, abdominal pain and itching being the most frequent. Positive serology and eosinophilia were present in 84.4% and 66.1%, respectively, of those patients for whom these data were available. Concomitant parasitic infections were reported in 23.5% of patients. Treatment, administered to 325 patients (82.9%), was extremely heterogeneous between and within centres; the most commonly used regimen was mebendazole 100 mg twice a day for 1 month. A total of 256 (65.3%) patients attended a first follow-up, median 3 months (interquartile range 2–12) after the first visit; 83.1% of patients having received treatment based on mebendazole and/or doxycycline, targeting Wolbachia, became amicrofilaremic, 41.1–78.4% of whom within 12 months from single treatment. Conclusions Lack of specific symptoms, together with the inconstant positivity of parasitological and antibody-based assays in the infected population, makes the clinical suspicion and screening for mansonellosis particularly difficult. Prospective studies evaluating prevalence of infection in migrants from endemic areas, infection-specific morbidity, presence of Wolbachia endosymbionts in M. perstans populations from different geographical areas and efficacy of treatment regimens are absolutely needed to optimize the clinical management of infection.

Facilitating access to medicines and continuity of care for Ukrainian refugees: exceptional response or the promise of more inclusive healthcare for all migrants?

Abstract: Department of Public Health, Institute of Tropical Medicine, Antwerpen, Belgium Institute for Infection and Immunity, St George’s, University of London, London, UK Department of Global Health, Boston University Scool of Public Health, Boston, Massachusetts, USA Department of Epidemiology & International Publich Health, School of Public Health, Bielefeld University, Bielefeld, Germany Center for Tropical Diseases, Ospedale Sacro Cuore Don Calabria, Negrar, Verona, Italy

Can Biomarkers of Oxidative Stress in Serum Predict Disease Severity in West Nile Virus Infection? A Pilot Study

Abstract: West Nile virus (WNV) can cause asymptomatic infection in humans, result in self-limiting febrile illness, or lead to severe West Nile Neuroinvasive disease (WNND). We conducted a pilot study to compare selected biomarkers of oxidative stress in sera of viremic West Nile virus patients and asymptomatic infected blood donors to investigate their potential as predictors of disease severity. We found that total oxidant status was elevated in WNND and in uncomplicated WNV infections (median 9.05 (IQR 8.37 to 9.74) and 7.14 (7.03 to 7.25) µmol H2O2 equiv./L, respectively) compared to asymptomatic infections (0.11 (0.07 to 0.19) µmol H2O2 equiv./L) (p = 0.048). MDA levels showed a similar trend to TOS, but differences were not significant at α = 0.05. Total antioxidant status did not differ significantly between different disease severity groups. Oxidative stress appears to be associated with more severe disease in WNV-infected patients. Our preliminary findings warrant prospective studies to investigate the correlation of oxidative stress with clinical outcomes and severity of WNV infection.

Management of imported complicated urogenital schistosomiasis in Europe: a TropNet retrospective study.

Abstract: BACKGROUND Schistosomiasis is a Neglected Tropical Disease (NTD) caused by trematodes of the genus Schistosoma. Schistosoma haematobium causes urogenital schistosomiasis (UGS), a chronic disease characterized by pathology of the urogenital tract leading to potentially severe morbidity for which the treatment is poorly standardized. We conducted a survey in TropNet centers on the clinical presentations and management strategies of complicated urogenital schistosomiasis (cUGS). METHODS We reviewed the clinical records of patients seen at TropNet centers over a 20-year timespan (January 2001-December 2020). Case definition for cUGS included the presence of urogenital cancer, obstructive uropathy, kidney insufficiency of all grades, and female or male infertility with signs of genital involvement. Collected data included demographic information, patient category (traveller or migrant), imaging data, microbiological data (serology results and presence/absence of eggs in urine), histological features, and outcome at last visit recorded. RESULTS Eight centres contributed with at least one case. Overall, 31 patients matched the inclusion criteria. Sub-Saharan Africa was the most likely place of infection for included patients. Median age was 30.6 years (range 21-46, IQR 27-33). Most patients (28/31, 90.3%) were males. Hydronephrosis was the most frequent complication, being present in eighteen (58.1%) patients, followed by cancer, present in five patients (16.1%); 27 patients (87.1%) required surgical management of some sort. Use of praziquantel varied across centres, with six different regimens employed. DISCUSSION Very few cases of cUGSs were found in our survey, possibly indicating underdiagnosis of this condition. Hydronephrosis was the most frequently observed urogenital complication, and most patients required invasive procedures. Infection by S. haematobium can result in considerable morbidity, resulting in clinically challenging presentations requiring a multidisciplinary approach. As such, development of common protocols for early diagnosis and treatment is urgently needed.

Acute hepatitis A in international travellers: a GeoSentinel analysis, 2008–2020

Abstract: Abstract Background Non-immune international travellers are at risk of acquiring hepatitis A. Although hepatitis A vaccination is recommended for unvaccinated travellers to high or intermediate hepatitis A virus endemicity, compliance with this recommendation is not universal. The main objective was to describe the demographic and travel characteristics of international travellers infected with hepatitis A during travel. Methods Available data on travellers with confirmed (positive molecular test) or probable (symptomatic individuals with a single positive IgM test) hepatitis A diagnosed during and after travel from January 2008 to December 2020 were obtained from the GeoSentinel Surveillance Network database. We analysed demographic and travel characteristics of infected travellers. Results Among 254 travellers with hepatitis A (185 confirmed and 69 probable), the median age was 28 years (interquartile range: 19–40), 150 (59%) were male, and among 54 travellers with information available, 53 (98%) were unvaccinated. The most common reasons for travel included tourism (n = 120; 47%) and visiting friends or relatives (VFR; n = 72; 28%). About two-thirds of VFR travellers with hepatitis A (n = 50; 69%) were younger than 20 years old. Hepatitis A was acquired most frequently in South-Central Asia (n = 63; 25%) and sub-Saharan Africa (n = 61; 24%), but 16 travellers (6%) acquired hepatitis A in regions with low endemicity including Western Europe (n = 7; 3%), the Caribbean (n = 6; 2%) and North America (n = 3; 1%). Median duration from illness onset to GeoSentinel site presentation was ~7 days (interquartile range : 4–14 days). Among 88 travellers with information available, 59% were hospitalized. Conclusions Despite availability of highly effective vaccines, travellers still acquire hepatitis A, even when traveling to low-endemicity destinations. Providing pre-departure hepatitis A vaccine to susceptible travellers is crucial to reducing travel-associated hepatitis A and should be offered to all travellers as part of the pre-travel consultation, regardless of destination.

Spleen nodules in Loa loa infection: re-emerging knowledge and future perspectives.

Abstract: Loiasis, the infection with the vector-borne filarial nematode Loa loa, is widely distributed in central and west Africa. Long considered a rather benign infection, recently loiasis with high microfilarial burden was associated with increased mortality risk. Eyeworm and Calabar swelling are pathognomonic signs of the infection, but other atypical, non-specific manifestations can also occur. For instance, splenic nodules have been seldom reported. In this Grand Round, we report two cases of loiasis in migrants who presented with spleen nodules, which could be followed up over time (up to 27 months) with multiple imaging techniques until their resolution. We comment on the clinical implications of these observations, including differential diagnosis with similar imaging findings, and critically review the evidence of spleen involvement in loiasis and other filarial infections.

Loiasis from where you don’t expect it: an illustrative case of misled diagnosis

Abstract: In the absence of pathognomonic signs, the diagnosis of filarial infections relies on geographical exposure and morphology of microfilariae, which requires expertise. We present a case of loiasis in a patient not reporting exposure in areas of known Loa loa endemicity, whose diagnosis was achieved by molecular analysis of microfilariae.

The challenge of infectious diseases consultations in the emergency department: an Italian nationwide survey.

Abstract: Diagnosis and management of infectious diseases (ID) at the emergency department (ED) are challenging due to the peculiar setting and the available diagnostic tools. The involvement of an ID consultant has been described to improve clinical outcomes and antimicrobial stewardship (AMS) programs. An online survey was sent to 100 Italian Departments of Infectious Diseases affiliated with the Italian Society of Infectious Diseases and Tropical Medicine (SIMIT). The primary objective of our study was to describe the characteristics of ID services in Italian EDs to identify possible challenges and shortcomings and provide tips to improve the management of patients. Secondary objectives included the evaluation of diagnostic capability and the management of patients with suspected or confirmed ID. Seventy-six out of the 100 SIMIT centers, 32 (42.1%) of which were teaching hospitals, answered the survey. In 62 (82.7%) centers, consultations were performed by the IDs specialist on call. In 29 (38.2%) centers, there was a formal AMS program, and 32 (42.7%) had protocols for antibiotic use in the ED. Microbiological tests to be performed before starting antibiotic treatment in the ED were clearly defined in 44 (57.9%) hospitals. This survey highlighted several challenges in the current organization of ID consultations in Italian EDs.

Dengue outbreak among travellers returning from Cuba-GeoSentinel surveillance network, January-September 2022.

Abstract: Increasing numbers of travellers returning from Cuba with dengue virus infection were reported to the GeoSentinel Network from June through September 2022, reflecting an ongoing local outbreak. This report demonstrates the importance of travellers as sentinels of arboviral outbreaks and highlights the need for early identification of travel-related dengue.