A machine learning approach for early identification of patients with severe imported malaria.

BACKGROUND: The aim of this study is to design ad hoc malaria learning (ML) approaches to predict clinical outcome in all patients with imported malaria and, therefore, to identify the best clinical setting. METHODS: This is a single-centre cross-sectional study, patients with confirmed malaria, consecutively hospitalized to the Lazzaro Spallanzani National Institute for Infectious Diseases, Rome, Italy from January 2007 to December 2020, were recruited. Different ML approaches were used to perform the analysis of this dataset: support vector machines, random forests, feature selection approaches and clustering analysis. RESULTS: A total of 259 patients with malaria were enrolled, 89.5% patients were male with a median age of 39 y/o. In 78.3% cases, Plasmodium falciparum was found. The patients were classified as severe malaria in 111 cases. From ML analyses, four parameters, AST, platelet count, total bilirubin and parasitaemia, are associated to a negative outcome. Interestingly, two of them, aminotransferase and platelet are not included in the current list of World Health Organization (WHO) criteria for defining severe malaria. CONCLUSION: In conclusion, the application of ML algorithms as a decision support tool could enable the clinicians to predict the clinical outcome of patients with malaria and consequently to optimize and personalize clinical allocation and treatment.

What is the impact of post-COVID-19 syndrome on health-related quality of life and associated factors: a cross-sectional analysis.

BACKGROUND: After the acute phase, symptoms or sequelae related to post-COVID-19 syndrome may persist for months. In a population of patients, previously hospitalized and not, followed up to 12 months after the acute infection, we aim to assess whether and to what extent post-COVID-19 syndrome may have an impact on health-related quality of life (HRQoL) and to investigate influencing factors. METHODS: We present the cross-sectional analysis of a prospective study, including patients referred to the post-COVID-19 service. Questionnaires and scales administered at 3, 6, 12 months were: Short-Form 36-item questionnaire (SF-36); Visual Analogue Scale of the EQ5D (EQ-VAS); in a subgroup, Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI-II) and Pittsburgh Sleep Quality Index (PSQI). Linear regression models were fitted to identify factors associated with HRQoL. RESULTS: We considered the first assessment of each participant (n = 572). The mean scores in SF-36 and in EQ-VAS were significantly lower than the Italian normative values and remained stable over time, except the mental components score (MCS) of the SF-36 and EQ-VAS which resulted in lower ratings at the last observations. Female gender, presence of comorbidities, and corticosteroids treatment during acute COVID-19, were associated with lower scores in SF-36 and EQ-VAS; patients previously hospitalized (54%) reported higher MCS. Alterations in BAI, BDI-II, and PSQI (n = 265)were associated with lower ratings in SF-36 and EQ-VAS. CONCLUSIONS: This study provides evidence of a significantly bad perception of health status among persons with post-COVID-19 syndrome, associated with female gender and, indirectly, with disease severity. In case of anxious-depressive symptoms and sleep disorders, a worse HRQoL was also reported. A systematic monitoring of these aspects is recommended to properly manage the post-COVID-19 period.

Systematic analysis of direct antiglobulin test results in post-artesunate delayed haemolysis.

BACKGROUND: Post-artesunate delayed haemolysis (PADH) is common after severe malaria episodes. PADH is related to the "pitting" phenomenon and the synchronous delayed clearance of once-infected erythrocytes, initially spared during treatment. However, direct antiglobulin test (DAT) positivity has been reported in several PADH cases, suggesting a contribution of immune-mediated erythrocyte clearance. The aim of the present study was to compare clinical features of cases presenting a positive or negative DAT. METHODS: Articles reporting clinical data of patients diagnosed with PADH, for whom DAT had been performed, were collected from PubMed database. Data retrieved from single patients were extracted and univariate analysis was performed in order to identify features potentially related to DAT results and steroids use. RESULTS: Twenty-two studies reporting 39 PADH cases were included: median baseline parasitaemia was 20.8% (IQR: 11.2-30) and DAT was positive in 17 cases (45.5%). Compared to DAT-negative individuals, DAT-positive patients were older (49.5 vs 31; p = 0.01), had a higher baseline parasitaemia (27% vs 17%; p = 0.03) and were more commonly treated with systemic steroids (11 vs 3 patients, p = 0.002). Depth and kinetics of delayed anaemia were not associated with DAT positivity. CONCLUSIONS: In this case series, almost half of the patients affected by PADH had a positive DAT. An obvious difference between the clinical courses of patients presenting with a positive or negative DAT was lacking. This observation suggests that DAT result may not be indicative of a pathogenic role of anti-erythrocytes antibodies in patients affected by PADH, but it may be rather a marker of immune activation.

An Inflammatory Profile Correlates With Decreased Frequency of Cytotoxic Cells in Coronavirus Disease 2019.

Increased production of inflammatory cytokines and myeloid-derived suppressor cells occurs in patients with coronavirus disease 2019. These inversely correlated with perforin-expressing natural killer (NK) and CD3+ T cells. We observed a lower number of perforin-expressing NK cells in intensive care unit (ICU) patients compared with non-ICU patients, suggesting an impairment of the immune cytotoxic arm as a pathogenic mechanism.

Legionella pneumonia: increased risk after COVID-19 lockdown? Italy, May to June 2020.

We report a case of Legionella pneumonia in a dishwasher of a restaurant in Rome, Italy, just after the end of the lockdown that was in place to control the SARS-CoV-2 epidemic. The case highlights the importance of strict monitoring of water and air systems immediately before reopening business or public sector buildings, and the need to consider Legionella infections among the differential diagnosis of respiratory infections after lockdown due to the ongoing COVID-19 pandemic.

Coronavirus disease (COVID-19) in a paucisymptomatic patient: epidemiological and clinical challenge in settings with limited community transmission, Italy, February 2020.

Data concerning the transmission of the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) in paucisymptomatic patients are lacking. We report an Italian paucisymptomatic case of coronavirus disease 2019 with multiple biological samples positive for SARS-CoV-2. This case was detected using the World Health Organization protocol on cases and contact investigation. Current discharge criteria and the impact of extra-pulmonary SARS-CoV-2 samples are discussed.

Five cases of Plasmodium vivax malaria treated with artemisinin derivatives: the advantages of a unified approach to treatment.

OBJECTIVES: In endemic countries with a high level of chloroquine resistance, Plasmodium vivax malaria is associated with high morbidity and mortality. In these areas, the dihydroartemisinin-piperaquine combination resulted in clinical response, a more rapid clearance of parasitaemia, compared to chloroquine therapies, and reduction of recrudescence or reinfection. METHODS: We describe five cases of Plasmodium vivax malaria in returning travelers treated with dihydroartemisinin-piperaquine. RESULTS: All patients showed the early parasite clearance and no side effects. Our preliminary results suggest that the dihydroartemisinin-piperaquine combination is effective and safe even in imported cases. CONCLUSIONS: A unified treatment policy using the artemisinin combination therapy should be adopted even in non-endemic countries and larger studies are underway to support this strategy.

Serological evaluation for Chagas disease in migrants from Latin American countries resident in Rome, Italy.

BACKGROUND: Chagas disease (CD) is a systemic parasitic infection caused by the protozoan Trypanosoma cruzi, whose chronic phase may lead to cardiac and intestinal disorders. Endemic in Latin America where it is transmitted mainly by vectors, large-scale migrations to other countries have turned CD into a global health problem because of its alternative transmission routes through blood transfusion, tissue transplantation, or congenital. Aim of this study was to compare the performance of two commercially available tests for serological diagnosis of CD in a group of Latin American migrants living in a non-endemic setting (Rome, Italy). The study was based on a cross-sectional analysis of seroprevalence in this group. Epidemiological risk factors associated to CD were also evaluated in this study population. METHODS: The present study was conducted on 368 subjects from the Latin American community resident in Rome. Following WHO guidelines, we employed a diagnostic strategy based on two tests to detect IgG antibodies against T. cruzi in the blood (a lysate antigen-based ELISA and a chemiluminescent microparticle CMIA composed of multiple recombinant antigens), followed by a third test (an immunochromatographic assay) on discordant samples. RESULTS: Our diagnostic approach produced 319/368 (86.7%) concordant negative and 30/368 (8.1%) concordant positive results after the first screening. Discrepancies were obtained for 19/368 (5.2%) samples that were tested using the third assay, obtaining 2 more positive and 17 negative results. The final count of positive samples was 32/368 (8.7% of the tested population). Increasing age, birth in Bolivia, and previous residence in a mud house were independent factors associated with T. cruzi positive serology. CONCLUSIONS: Serological diagnosis of CD is still challenging, because of the lack of a reference standard serological assay for diagnosis. Our results reaffirm the importance of performing CD screening in non-endemic countries; employing a fully automated and highly sensitive CMIA assay first could be a cost- and resource-effective strategy for mass screening of low-risk patients. However, our results also suggest that the WHO strategy of using two different serological assays, combined with epidemiological information, remains the best approach for patients coming from endemic countries.

Pulmonary measles disease: old and new imaging tools.

BACKGROUND: Measles virus can cause lower respiratory tract infection, so that chest radiography is necessary to investigate lung involvement in patients with respiratory distress. PURPOSE: To assess measles pneumonia imaging during the measles outbreak occurred in 2016-2017 in Italy. MATERIAL AND METHODS: We retrospectively observed adult patients with a serological diagnosis of measles, who underwent chest-X rays for suspected pneumonia. If a normal radiography resulted, the patient underwent unenhanced CT. A CT post processing software package was used for an additional quantitative lung and airway involvement analysis . RESULTS: Among 290 patients affected by measles, 150 underwent chest-X ray. Traditional imaging allowed the pneumonia diagnosis in 114 patients (76%). The most frequent abnormality at chest X-rays was bronchial wall thickening, observed in 88.5% of the cases; radiological findings are faint in the 25% of the cases (29/114 patients). In nine subjects with a normal chest X-ray, unenhanced CT with a quantitative analysis was performed, and depicted features consistent with constrictive bronchiolitis. CONCLUSION: Measles may produce bronchiolitis and pneumonia. In the cases in which involvement of pulmonary parenchyma is not sufficient to result in radiological abnormalities, CT used with a dedicated postprocessing software package, provides an accurate lungs and airways analysis, also determining the percentage of lung involvement.

Dengue fever as autochthonous infectious disease in Italy: Epidemiological, clinical and virological characteristics.

BACKGROUND: Since August to November 2023, 82 cases of autochthonous or non-travel related Dengue virus (DENV) infection have been reported in Italy, highlighting a concerning trend of local transmission. We describe the clinical and laboratory findings of 10 autochthonous DENV in the metropolitan area of Rome admitted to the Lazzaro Spallanzani National Institute for Infectious Diseases. METHOD AND RESULTS: Ten patients (3 males, 7 females; median age: 51) with classic dengue fever symptoms were admitted between August and November 2023. Laboratory tests confirmed dengue infection through DENV non-structural protein 1 and/or immunoglobulins (IgM/IgG) positive tests, moreover leukopenia, thrombocytopenia, elevated transaminases were detected. A subset of patients underwent extensive biological sampling, including real-time RT-PCR and immunofluorescence, to monitor DENV-RNA and antibody levels over 30 days. DENV-1 was detected in 8 patients and DENV-3 in 2. Upon admission specific IgM antibodies were found in 7 patients while IgG antibodies in 4 patients. DENV RNA was consistently detected in blood within the first 8 days but was less common in saliva and urine. No DENV RNA was detected after day 24. CONCLUSION: These findings contribute to the understanding of the clinical course of DENV infection in a non-endemic setting as integrated epidemiological and clinical model to increase syndromic surveillance and timely diagnosis of DENV infections.

Cognitive outcomes and psychological symptoms in an Italian cohort with post-acute COVID-19 condition (PACC).

Background: We aim to investigate the proportion of patients (pts) with long-term cognitive outcomes (CO) of PACC and identify associated features. Methods: We assessed participants through a neuropsychological assessment. The chi-square test was used for comparisons according with time of NPA (within or beyond 6 months since COVID19) and with previously hospitalization status (hospitalized patients, PH; not hospitalized patients, nPH). Results: 520 participants: mean age 54 years (SD 12), 53 % female, 14 years of education (SD 3.4), 35 % with >1 comorbidity, 48 % previously hospitalized. Overall, we found CO in 89 % of pts, in particular 88 % evaluated in w6M and 89 % in b6M (p = 0.801) while 90 % and 87 % in nPH and PH, respectively (p = 0.239). By fitting multivariable analysis, PH for COVID19 and female gender were associated with an increased risk of an altered PSQI [Odd Ratio, OR 2.48, 95 % CI 1.54 to 3.99, p < 0.001 and OR 2.59, 95 % CI 1.60 to 4.17, p < 0.001, respectively) and BAI [F vs M: OR 1.67, 95 % CI 1.16 to 2.40, p = 0.005). Conclusions: We show a substantial proportion of PACC-CO; hospitalization leads to impaired memory, anxiety and sleep disorders. Women seem to be at higher risk for anxious-depressive symptoms and worse sleep quality than men.

Concomitant Parenchymal, Subarachnoid, and Ventricular Neurocysticercosis in Rome, Italy: A Case Report with a 4-Year Follow-Up.

Neurocysticercosis (NCC) is caused by the larval stage of Taenia solium. This parasitic disease is endemic in many areas of the world and is emerging in Europe. NCC can affect different brain regions, but simultaneous involvement of the parenchymal, subarachnoid, and ventricular regions is rare. We report the case of a 39-year-old woman from Honduras, resident in Rome for 10 years, who presented to the Emergency Department complaining of headaches, transient hemianopsia, and bilateral papilledema. MRI showed a concomitant parenchymal, subarachnoid, and ventricular involvement in the brain. T. solium IgG antibodies were detected in the blood. The etiological diagnosis of NCC was obtained by identifying T. solium in cerebrospinal fluid using Next Generation Sequencing. Endoscopic neurosurgery with the placement of a ventricular shunt and medical long-term anti-parasitic treatment with a cumulative number of 463 days of albendazole and 80 days of praziquantel were performed. A successful 4-year follow-up is reported. NCC is one of the most common parasitic infections of the human CNS, but it is still a neglected tropical disease and is considered to be an emerging disease in Europe. Its diagnosis and clinical management remain a challenge, especially for European clinicians.

Efficacy of a Multistrain Synbiotic Treatment in Acute and Post-Acute COVID-19 Patients: A Double-Blind, Placebo-Controlled Randomized Trial.

BACKGROUND AND AIMS: Several studies reported the effect of COVID-19 on inducing gut dysbiosis, which is also correlated with disease severity. This study aims to investigate the effect of a nutraceutical formula on the shift of microbiota profiles and, secondly, on the clinical-pathological parameters of acute and post-acute COVID-19 patients. METHODS: In this randomised, double-blind, placebo-controlled trial conducted at National Institute for Infectious diseases (INMI) Lazzaro Spallanzani (Italy), 52 patients were randomly assigned (1:1) to receive a multistrain synbiotic formula (Kebirah®) or placebo orally for 35 days at COVID-19 diagnosis. Health professionals, investigators, and patients were masked to group assignments. The V3-V4 hypervariable region of 16S rRNA gene sequencing was employed to study the gut microbiota composition in the two groups. RESULTS: Supplementation with Kebirah® prevented the decrease in the Shannon diversity index of gut microbiota, which was instead observed in patients receiving the placebo. In addition, decreases in lymphocyte count and haemoglobin levels were observed only in the placebo group and not in the treated group, which was also characterised by an amelioration of the gut microbial profile, with an enrichment in beneficial bacteria and a preservation of species diversity. CONCLUSIONS: Our data suggest that modulating the gut microbiota in acute disease through administration of a specific symbiotic formula could be a useful strategy in the frame of SARS-CoV-2 infections.

Chagas Disease in the Non-Endemic Area of Rome, Italy: Ten Years of Experience and a Brief Overview.

Chagas disease (CD) is a parasitic infection endemic in Latin America and also affects patients in Western countries due to migration flows. This has a significant impact on health services worldwide due to its high morbidity and mortality burden. This paper aims to share our experience at the National Institute for Infectious Diseases "Lazzaro Spallanzani", IRCCS, in Rome, Italy, where to date, a total of 47 patients-mainly Bolivian women-diagnosed with CD have received treatment with benznidazole, with all but one presenting with chronic disease. Most of the patients were recruited through the first extensive screening program held in 2014 at our Institute. About a quarter of our patients showed adverse effects to benznidazole, including a case of severe drug-induced liver injury, but 83% completed a full course of treatment. In addition to the description of our cohort, the paper reports a brief overview of the disease compiled through a review of the existing literature on CD in non-endemic countries. The growing prevalence of CD in Western countries highlights the importance of screening at-risk populations and urges public concern and medical awareness about this neglected tropical disease. There are still many unanswered questions that need to be addressed to develop a personalized approach in treating patients.

MPXV DNA kinetics in bloodstream and other body fluids samples.

Since spring 2022, the global epidemiology of the monkeypox virus (MPXV) has changed. The unprecedented increase of human clade II MPXV cases worldwide heightened concerns about this emerging zoonotic disease. We analysed the positivity rates, viral loads, infectiousness, and persistence of MPXV DNA for up to 4 months in several biological samples from 89 MPXV-confirmed cases. Our data showed that viral loads and positivity rates were higher during the first two weeks of symptoms for all sample types. Amongst no-skin-samples, respiratory specimens showed higher MPXV DNA levels and median time until viral clearance, suggesting their usefulness in supporting MPXV diagnosis, investigating asymptomatic patients, and monitoring viral shedding. Infectious virus was cultured from respiratory samples, semen, and stools, with high viral loads and collected within the first 10 days. Notably, only one saliva and one semen were found positive for viral DNA after 71 and 31 days from symptoms, respectively. The focus on bloodstream samples showed the best testing sensitivity in plasma, reporting the overall highest MPXV DNA detection rate and viral loads during the 3-week follow-up as compared to serum and whole-blood. The data here presented can be useful for MPXV diagnostics and a better understanding of the potential alternative routes of its onward transmission.

Pharyngo-tonsillar involvement of Mpox in a cohort of men who have sex with men (MSM): A serious risk of missing diagnosis.

During the 2022-outbreak, peculiar clinical presentations of Mpox have been described, some of which can make the diagnosis of the disease extremely challenging. Here we report a case series of fourteen patients with Mpox pharynogotonsillar involvement (PTI) seen at National Institute for Infectious Diseases, "Lazzaro Spallanzani", in Rome, Italy from May to September 2022. All included patients were men who have sex with men (median age 38 years) reporting unprotected sex within three weeks from symptoms onset. Seven out of fourteen patients needed hospitalization due to uncontrolled pain, reduced airspace and difficulty swallowing, of whom five were effectively treated with tecovirimat or cidofovir. The remaining two patients were treated with symptomatic drugs. The typical Mpox muco-cutaneous manifestations were not observed simultaneously with PTI in three patients, two of whom developed the lesions after several days, while one never manifested them. Polymerase Chain Reaction (PCR) for Mpox virus was positive in oropharyngeal swab, saliva and serum. Although PTI occurs in only a small percentage of Mpox cases, its diagnosis is of utmost importance. In fact, this localization, if not identified, could lead to serious complications in the absence of early antiviral treatment and to missed diagnosis with an increased risk of disease transmission.

Predictors of Mortality and Orotracheal Intubation in Patients with Pulmonary Barotrauma Due to COVID-19: An Italian Multicenter Observational Study during Two Years of the Pandemic.

Introduction: Coronavirus disease 2019 (COVID-19) is a significant and novel cause of acute respiratory distress syndrome (ARDS). During the COVID-19 pandemic, there has been an increase in the incidence of cases involving pneumothorax and pneumomediastinum. However, the risk factors associated with poor outcomes in these patients remain unclear. Methods: This observational study collected clinical and imaging data from COVID-19 patients with PTX and/or PNM across five tertiary hospitals in central Italy between 1 March 2020 and 1 March 2022. This study also calculated the incidence of PTX and PNM and utilized multivariable regression analysis and Kaplan-Meier curve analysis to identify predictor factors for 28-day mortality and 3-day orotracheal intubation after PTX/PNM. This study also considered the impact of the three main variants of concern (VoCs) (alfa, delta, and omicron) circulating during the study period. Results: During the study period, a total of 11,938 patients with COVID-19 were admitted. This study found several factors independently associated with a higher risk of death in COVID-19 patients within 28 days of pulmonary barotrauma. These factors included a SOFA score ≥ 4 (OR 3.22, p = 0.013), vasopressor/inotropic therapy (OR 11.8, p < 0.001), hypercapnia (OR 2.72, p = 0.021), PaO2/FiO2 ratio < 150 mmHg (OR 10.9, p < 0.001), and cardiovascular diseases (OR 7.9, p < 0.001). This study also found that a SOFA score ≥ 4 (OR 3.10, p = 0.015), PCO2 > 45 mmHg (OR 6.0, p = 0.003), and P/F ratio < 150 mmHg (OR 2.9, p < 0.042) were factors independently associated with a higher risk of orotracheal intubation (OTI) within 3 days from PTX/PNM in patients with non-invasive mechanical ventilation. SARS-CoV-2 VoCs were not associated with 28-day mortality or the risk of OTI. The estimated cumulative probability of OTI in patients after pneumothorax was 44.0% on the first day, 67.8% on the second day, and 68.9% on the third day, according to univariable survival analysis. In patients who had pneumomediastinum only, the estimated cumulative probability of OTI was 37.5%, 46.7%, and 57.7% on the first, second, and third days, respectively. The overall incidence of PTX/PNM among hospitalized COVID-19 patients was 1.42%, which increased up to 4.1% in patients receiving invasive mechanical ventilation. Conclusions: This study suggests that a high SOFA score (≥4), the need for vasopressor/inotropic therapy, hypercapnia, and PaO2/FiO2 ratio < 150 mmHg in COVID-19 patients with pulmonary barotrauma are associated with higher rates of intubation, ICU admission, and mortality. Identifying these risk factors early on can help healthcare providers anticipate and manage these patients more effectively and provide timely interventions with appropriate intensive care, ultimately improving their outcomes.