Risk for SARS-CoV-2 Infection in Healthcare Workers, Turin, Italy.

We measured severe acute respiratory syndrome coronavirus 2 spike protein subunits S1/S2 antibodies by using capillary electrophoresis and a chemiluminescence immunoassay for 5,444 active healthcare workers in Italy. Seroprevalence was 6.9% and higher among participants having contact with patients. Seroconversion was not observed in 37/213 previously infected participants.

Cerebrospinal fluid biomarkers in patients with central nervous system infections: a retrospective study.

BACKGROUND: Central nervous system (CNS) may be infected by several agents, resulting in different presentations and outcomes. Analysis of cerebrospinal fluid (CSF) markers could be helpful to differentiate specific conditions and setting an appropriate therapy. METHODS: Patients presenting with signs and symptoms were enrolled if, before receiving a diagnostic lumbar puncture, signed a written informed consent. We analyzed CSF indexes of blood-brain barrier permeability (CSF to serum albumin ratio or CSAR), inflammation (CSF to serum IgG ratio, neopterin), amyloid deposition (1-42 ß-amyloid), neuronal damage (Total tau (T-tau), Phosphorylated tau (P-tau), and 14.3.3 protein) and astrocyte damage (S-100ß). RESULTS: Two hundred and eighty-one patients were included: they were mainly affected by herpesvirus encephalitis, enterovirus meningoencephalitis, bacterial meningitis (Neisseria meningitidis and Streptococcus pneumoniae), and infection by other etiological agents or unknown pathogen. Their CSF features were compared with HIV-negative patients and native HIV-positive individuals without CNS involvement. 14.3.3 protein was found in bacterial and HSV infections while T-tau and neopterin were abnormally high in the herpesvirus group. P-tau, instead, was elevated in enterovirus meningitis. S-100ß was found to be high in patients with HSV-1 and HSV-2 infections but not in those with Varicella Zoster Virus (VZV). Thirty-day mortality was unexpectedly low (2.7%): patients who died had higher levels of T-tau and, significantly, lower levels of Aß1-42. CONCLUSION: This work demonstrates that CSF biomarkers of neuronal damage or inflammation may vary during CNS infections according to different causative agents. The prognostic value of these biomarkers needs to be assessed in prospective studies.

Louseborne Relapsing Fever among East African Refugees, Italy, 2015.

During June 9-September 30, 2015, five cases of louseborne relapsing fever were identified in Turin, Italy. All 5 cases were in young refugees from Somalia, 2 of whom had lived in Italy since 2011. Our report seems to confirm the possibility of local transmission of louse-borne relapsing fever.

Extended and Continuous Infusion of Novel Protected ß-Lactam Antibiotics: A Narrative Review.

Consolidated data from pharmacokinetic and pharmacodynamic studies support the administration of ß-lactam antibiotics in prolonged infusion (i.e., extended or continuous) to optimize therapeutic efficacy by increasing the probability of attaining maximal bactericidal activity. This is the longest possible time during which the free drug concentrations are approximately four-fold the minimum inhibitory concentration between dosing intervals. In the context of antimicrobial stewardship strategies, achieving aggressive pharmacokinetic and pharmacodynamic targets is an important tool in the management of multi-drug resistant (MDR) bacterial infections and in the attainment of mutant preventing concentrations. However, prolonged infusion remains an unexploited resource. Novel ß-lactam/ß-lactamase inhibitor (ßL/ßLI) combinations (ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-cilastatin-relebactam) have been released in recent years to face the emerging challenge of MDR Gram-negative bacteria. Pre-clinical and real-life evidence has confirmed the promising role of prolonged infusion of these molecules in specific settings and clinical populations. In this narrative review we have summarized available pharmacological and clinical data, future perspectives, and current limitations of prolonged infusion of the novel protected ß-lactams, their application in hospital settings and in the context of outpatient parenteral antimicrobial therapy.

Trichinella britovi outbreak in Piedmont, North-West Italy, 2019-2020: Clinical and epidemiological insights in the one health perspective.

BACKGROUND: Trichinellosis, a foodborne zoonosis due to nematodes of the genus Trichinella, occurs in the form of outbreaks following meat consumption. North Italy has been rarely involved. We report here the most significant wildlife derived trichinellosis outbreak ever registered in the Piedmont region. METHOD: We retrospectively included 96 outpatients referred to our institution (December 20th, 2019-January 15th, 2020) 2020 after consuming raw sausages prepared from a single wild boar hunted in the Susa Valley, 59 km away from Torino, in November 2019. RESULTS: We confirmed 35 cases and found additional 10 probable/suspected cases. Our cohort found that 47% of patients were symptomatic, with a median time from symptoms to presentation at clinic and serology testing of 14 days. Peripheral blood eosinophilia >500/µl and CK alterations were common. Further qualitative and quantitative analysis at the International Trichinella Reference Center c/o ISS, Rome identified T. britovi as the causative agent. CONCLUSIONS: No autochthonous human case has ever been detected in Torino province, and a single wild boar has tested positive for Trichinella since active surveillance was implemented in 2013. This outbreak should raise attention on the preventive role of veterinary surveillance and the need to optimize sampling procedures and targeted health education.

Presence of Epstein-Barr virus DNA in cerebrospinal fluid is associated with greater HIV RNA and inflammation.

OBJECTIVE: The current study aimed to investigate whether cerebrospinal fluid (CSF) Epstein-Barr virus (EBV) or cytomegalovirus (CMV) DNA was associated with viral, inflammatory and neuronal damage biomarkers in people living with HIV (PLWH). DESIGN: A cross-sectional diagnostic study on CSF fluid samples in patients undergoing lumbar punctures for clinical reasons, to better understand the role of EBV and CMV in the CNS on HIV RNA replication, blood-brain-barrier (BBB) damage and biomarkers of neuronal damage/inflammation. METHODS: EBV, CMV DNA and HIV RNA were measured on CSF, through real time (RT)-PCR, from PLWHs undergoing lumbar punctures for clinical reasons (excluding oncho-haematological comorbidities). Immune-enzymatic assays evaluated blood-brain barrier inflammation and damage. Patients were stratified according to plasma HIV RNA levels in viremic (≥50 copies/ml) and aviremic (<50 copies/ml). RESULTS: We included 297 participants. Among 167 viremic patients CSF EBV and CMV DNA were detectable in 42 (25.1%) and 10 (6.3%) participants; among 130 aviremic individuals CSF EBV and CMV DNA were detectable in 12 (9.2%) and 0 (0%) participants, respectively. In viremic group detectable CSF EBV DNA was associated with CSF pleocytosis (P < 0.001), higher CSF HIV RNA (P < 0.001) and neopterin levels (P = 0.002). In aviremic participants detectable EBV DNA was associated with pleocytosis (P = 0.056), higher neopterin (P = 0.027) and immune globulins (P = 0.016) in the CSF; CSF escape was more common in those with detectable EBV DNA (50 vs. 21.2%, P = 0.036). CONCLUSION: EBV DNA was frequently detected in the CSF of viremic and fewer aviremic patients on antiretroviral treatment. In PLWH without clinical evidence of encephalitis CSF EBV DNA was associated with higher biomarkers levels of neuronal damage/inflammation. The role of EBV reactivation in HIV-associated central nervous system disorders warrants further studies.

Klebsiella pneumoniae meningitis in a 38-year-old Chinese traveller with impaired glucose tolerance: a new emerging syndrome?

Early diagnosis and appropriate empirical treatment of bacterial meningitis reduce morbidity and mortality. Prevalence rates of different causative pathogens associated with bacterial meningitis can depend on age, the underlying medical condition, way of infection and geographical distribution. Klebsiella pneumoniae represents an infrequent cause of community-acquired meningitis in South-East Asia and North-East Asia, where it accounts for 20% of all bacterial meningitis, frequently associated with septic metastatic complications. We describe a case of K. pneumoniae meningitis, diplopia and chemosis in a recently immigrated patient with impaired glucose tolerance. The reason for the high prevalence of metastatic septic infections caused by K. pneumoniae in Taiwan and South-East Asia remains unclear: high prevalence in this area of serotype K1 and K2 and the expression of a novel locus called magA conferring to bacterium an elevated phagocytosis resistance and an active proliferation ability have been suggested. A high degree of suspicion for this etiology must be taken into account in immigrants from China and Taiwan. Due to a very high lethality, guidelines on empiric treatment should be considered in the management of bacterial meningitis, with the patients geographical origin and the clinical syndrome (meningitis and endophtalmitis) as potential risk factors for K. pneumoniae infection.

[Primary soft tissue and tenosynovial tuberculosis after needlestick injury in a surgeon]. / Tubercolosi primaria tenosinoviale e dei tessuti molli da inoculazione in un chirurgo.

We describe the case of a surgeon, who pricked himself with a needle used to drain a paravertebral abscess in a patient from Sudan. He lost this patient at follow up. Six weeks later, the surgeon developed oedema of his left hand and wrist. He started antibiotics, amoxicillin/clavulanate plus ciprofloxacin 2 weeks, without any improvement. He came to our centre for examination, and by chance his patient had been admitted to our ward the day before, and had died during the night of disseminated tuberculosis. The surgeon was treated with rifampin, isoniazid and pyrazinamide (3 drugs 2 months, followed by rifampin plus isoniazid for further 7 months) with rapid improvement. He could start his job again after 5 months. To our knowledge, this is the first case of inoculation tuberculosis transmitted to a surgeon, while other cases in health care workers (internists, pathologists, nurses...) have already been well described.

Laboratory findings in Zika infection: The experience of a reference centre in North-West Italy.

BACKGROUND: Zika virus (ZIKV) remains a public health concern due to its association with fetal malformation and neurologic disease. OBJECTIVE: To report a reference centre experience on ZIKA virus (ZIKV) infection in travelers from epidemic countries from January 1 to September, 30, 2016 in Italy North-West (a geographic area covering 4.424 million inhabitants, corresponding to almost 73% of Italy North-West area). STUDY DESIGN: One hundred and twelve febrile travelers were studied to rule out a tropical fever [e.g. malaria, dengue (DENV), chikungunya (CHIKV), West Nile (WNV) and ZIKV]. Molecular tests for detecting ZIKV RNA were applied on serum or urine as well as IgG and IgM specific serology. RESULTS: ZIKV was the most frequent "tropical infection (11.6%) with 12 infected travelers and one sexual partner of an infected traveler. At the time of the diagnosis, ZIKV RNA was detected in the blood from 9 patients (69%) within 7 days from symptom onset; afterwards, the virus was detected only in urine (5 patients) and ZIKV IgM was reactive in 9 patients (69%). Travelers with ZIKV infection tested negative for DENV, CHIKV, WNV and malaria and completely recovered. Other infections identified in travelers were DENV (5 patients, 4.5%), CHIKV (1, 0.9%), malaria (Plasmodium vivax, 1, 0.9%), measles (1, 0.9%) and tuberculosis (1, 0.9%). CONCLUSIONS: The etiologic diagnosis of a febrile illness in travelers where ZIKV is endemic is highly desirable as they are sentinel of a challenging epidemiology including the risk of autochthonous transmission in non endemic countries where the competent or carrier vector is present.

High Incidence of Infections in HIV-positive Patients Treated for Lymphoproliferative Disorders.

BACKGROUND: Lymphoproliferative disorders are frequently diagnosed in HIV-positive patients and severe infections may occur during antineoplastic treatments: the incidence and impact of such events are not well-characterized. OBJECTIVE: To describe the occurrence and mortality of incident infections in HIV-positive individuals treated for lymphoproliferative disorders. METHODS: A retrospective study in HIV-positive adults with lymphoproliferative disorders (2000- 2012) who were hospitalised to receive antineoplastic chemotherapy; antimicrobial prophylaxis with alternate day co-trimoxazole (800/160 mg) was administered to all individuals. RESULTS: 103 patients were included: mostly males (81, 78.6%), Caucasians (101, 98.1%), with a median age of 43 years (39-51). Fifty-eight (56.3%) patients had non-Hodgkin's lymphoma (NHL), thirty-two (29.1%) had Hodgkin's lymphoma (HL) and ten patients (9.7%) had Burkitt's lymphoma (BL). Five year survival was 63.1%: the best survival rates were reported in HL (78.1%), followed by NHL (58.6%) and BL (50%). Forty-four patients (42.7%) developed 82 infections during follow up: identified causative agents were bacteria (35, 42.7%), viruses (28, 34.1%), mycobacteria (7, 8.5%), protozoa (7, 8.5%) and fungi (5, 6.1%). Cytomegalovirus infections (n=17, including 5 endorgan diseases) emerged 53 days after the diagnosis: multivariate analysis showed CD4+ cell count <100/uL as the only independently associated factor (p<0.001, aOR=23.5). Two factors were associated with mortality risk: an IPI/IPS-score of >2 (p=0.004, aOR=6.55) and the presence of CMV disease (p=0.032, aOR=2.73). CONCLUSION: HIV positive patients receiving treatment for lymphoproliferative disorders suffer from a high incidence of infections and associated mortality risk. Tailored prophylactic strategies need to be considered in this setting.

Pharmacodynamic analysis of antimalarials used in Plasmodium falciparum imported malaria in northern Italy.

BACKGROUND: Conventional treatment of imported malaria in Italy consists of quinine or mefloquine. Since beta-arthemeter is now available, an open-label pharmacodynamic analysis was performed in 73 adults with uncomplicated Plasmodium falciparum malaria. In vitro susceptibility to mefloquine and quinine was evaluated at admission. METHODS: According to clinical status, baseline parasitemia (P(0)), and premunition, the patients received intravenous quinine, oral mefloquine, or beta-arthemeter. The following parameters were measured: parasitemia at 0, 6, 12, and 24 hours and then every 24 hours until negative; time to 50%, 90%, and 100% reduction in parasite density (PC(50), PC(90), and PCT); parasite reduction ratio at 24 and 48 hours (PRR(24) and PRR(48)); percentage of patients with undetectable parasitemia at 48 hours (PPUP(48)); time required to eradication; in vitro susceptibility to mefloquine and quinine by World Health Organization Microtest Mark III. RESULTS: Of the study patients, 54.8% were immigrants from malaria-endemic countries. All the infections were acquired in Africa. All the patients were treated successfully. According to the pharmacodynamic parameters measured, no significant differences were recorded among patients with or without prior exposure to malaria. Pharmacodynamic comparison was performed between quinine and beta-arthemeter. Significantly higher clearance times were recorded for beta-arthemeter vs quinine (PC(50), PC(90), and PCT: 16.8, 42.6, and 72 h for quinine vs 7.9, 12.2, and 48 h for beta-arthemeter; p values: .02, < .0001, and .008, respectively). The number of patients who obtained a PPUP(48) with beta-arthemeter was higher than with quinine (66.7 vs 9.1%, p < .003), and PRR(24) was significantly higher in beta-arthemeter-treated patients (617 vs 3.15, p = .0001). PRR(48) and time to eradication were not measurable in the beta-arthemeter group (negative P at 48 h in most cases). Two recrudescences occurred after 5 and 7 days of beta-arthemeter monotherapy. All strains were fully susceptible to quinine and mefloquine. CONCLUSIONS: Pharmacodynamic properties of mefloquine and quinine are in the range reported in literature. The better PCT and pharmacodynamics of beta-arthemeter suggest that it could be used as a first-line agent, coadministered with mefloquine.

A clinical approach for cardiovascular monitoring of HIV-infected patients. Results from an observational cohort study.

BACKGROUND: HIV infection is one of the leading causes of acquired heart disease. Because of its high diffusion, systematic echocardiographic monitoring has been proposed to exclude cardiovascular involvement in these patients. The aim of this study was to evaluate an alternative clinical approach by which echocardiographic screening is limited to patients with a clinical suspicion of heart disease. METHODS: We studied 2030 consecutive HIV-infected patients admitted to a tertiary referral hospital (group A). History, physical examination, ECG, and chest X-ray were used to screen HIV-infected patients for cardiovascular involvement. Selected patients were extensively studied, first of all by echocardiography. Cardiovascular and non-cardiovascular deaths were recorded: RESULTS: Cardiovascular involvement was clinically suspected in 201 patients (9.9%; group B). Among them a higher extracardiac mortality was found in presence of pericardial disease (odds ratio [OR] 4.27, 95% confidence interval [CI] 2.01-9.09), while a higher cardiovascular mortality was recorded for patients with cardiomyopathy or myocarditis (OR 2.72, 95% CI 1.09-6.81), and right ventricular dysfunction and/or pulmonary hypertension (OR 4.67, 95% CI 1.44-15.2). Compared with group A, patients in group B had a significantly increased cardiac death rate (0.114 vs 0.018, p < 0.001). A positive echocardiogram slightly increased this rate (from 0.114 to 0.164, p = NS), whereas a negative echocardiogram significantly decreased the cardiac death rate (0.015 vs 0.164, p = 0.004). CONCLUSIONS: Clinical selection of HIV-infected patients with suspected cardiovascular involvement may help identify patients with higher frequency of cardiovascular involvement. Among these patients, echocardiography may be a useful screening tool in those at high risk for cardiovascular death.

Are the Duke criteria really useful for the early bedside diagnosis of infective endocarditis? Results of a prospective multicenter trial.

BACKGROUND: To date, no studies have evaluated the usefulness of the Duke vs the modified Duke criteria for the early diagnosis of infective endocarditis (IE), nor is it known whether a probabilistic approach may be useful in establishing an early clinical diagnosis of IE. The aim of this study was (1) to assess and compare the clinical usefulness of the Duke vs the modified Duke criteria for the early diagnosis of IE, and (2) to evaluate the diagnostic utility of a probabilistic approach based on the echocardiographic criterion. METHODS: From January 2000 to December 2001, 267 consecutive patients with suspected IE were enrolled in a prospective multicenter trial. RESULTS: IE was diagnosed in 147 cases (55%) and rejected in 120 cases (45%). The Duke and the modified Duke criteria had a high similar sensitivity, specificity and accuracy. The time to diagnosis was 8.15 +/- 7.4 days for the Duke criteria and 8.18 +/- 7.1 days for the modified Duke criteria. The time to diagnosis based on a probabilistic approach was shorter than that based on the Duke and the modified Duke criteria (4.96 +/- 7.1 days, for all p < 0.001). CONCLUSIONS: Although the Duke and the modified Duke criteria have a very similar sensitivity, specificity and accuracy, the delay in the time to diagnosis may be significant. A probabilistic approach based on clinical suspicion and echocardiographic evidence may be useful for decision-making, whilst awaiting case definition by means of the Duke criteria.

Puumala virus pulmonary syndrome in a Romanian immigrant.

Hantaviruses belong to the Bunyaviridae family, which is comprised of Bunyavirus, Phlebovirus, Nairovirus, and Hantavirus. Euroasiatic Hantaviruses belong to two distinct subfamilies: Murinae (comprising Hantaan, Dobrava, and Seoul viruses), which are responsible for hemorrhagic fever with renal syndrome (HFRS), and Arvicolinae (comprising Puumala virus), responsible for nephropathia epidemica (NE) and HFRS. On the contrary, the New World Hantavirus belongs to the Sigmodontinae subfamily and includes the North American viruses: Sin Nombre, Monongahela; New York, Bayou, Black Creek Canal, and the South American, which comprise the Andes, Oran, Lechiguanas, Laguna Negra, Juquitiba; both groups are responsible for the hantavirus pulmonary syndrome (HPS).

Recent outbreak of aseptic meningitis in Italy due to Echovirus 30 and phylogenetic relationship with other European circulating strains.

BACKGROUND: Enteroviruses (EVs) are common human viral pathogens, causing a variety of diseases, including aseptic meningitis. Recently, EV aseptic meningitis outbreaks have been reported across Europe, but, in Italy, knowledge of recent EV molecular epidemiology is very limited. OBJECTIVES: We report an outbreak of EV aseptic meningitis in 10 adults in North-Western Italy, from October to November 2012. Patients were parents or close relatives of children <5 years old attending the same class of a nursery school, suffering from a mild febrile upper respiratory disease. Phylogenetic relationship with other European circulating strains was analyzed updating E30 circulation in Italy in recent years. STUDY DESIGN: EVs were detected from cerebrospinal fluid (CSF) specimens with a real-time reverse transcription polymerase chain reaction and virus isolation was achieved from rectal and pharyngeal swabs. For cluster definition and phylogenetic studies, viral VP1 region was directly amplified and sequenced from CSF. RESULTS: EVs were identified in CSF from all patients and from rectal and pharyngeal swabs in 7 of them. Direct sequencing of CSF revealed the presence of the same Echovirus 30 (E30) in all patients and phylogenetic analysis identified it as a diverging clade within E30 genotype VII, the most recent strain circulating in UK, Finland and Denmark since 2006. CONCLUSION: Molecular techniques allowed the rapid identification and typing of E30 from CSF. Phylogenetic analysis revealed that the cluster might be due to a new E30 variant within the genotype VII currently circulating in Europe, thus updating the epidemiology of EV circulation in Italy.