Zika Virus: a Review from the Virus Basics to Proposed Management Strategies

This review aims to summarize the body of knowledge available on Zika virus to date. A comprehensive review of the scientific literature on Zika virus was performed with the aim to stress relevant aspects for healthcare professionals in the non-endemic areas. For several years, the Zika virus infection was considered an extremely rare exotic disease with poor clinical relevance. However, Zika virus has recently gained the attention of the scientific community and public opinion since the virus spread to the Pacific islands and the South America in an unprecedented epidemic, and additionally due to the definitive evidence that the infection could be complicated by Guillain-Barré syndrome, passed through vertical transmission, and result in central nervous system abnormalities (including microcephaly) of the fetus. Studies and scientific evidence on the complications associated with Zika virus infection are growing day by day. It is advisable that the healthcare professionals working in non-endemic areas maintain full awareness on this issue in order to practice proper management of the imported cases of Zika virus infection

Canine Trypanosoma cruzi infection in the Bolivian Chaco

A cross-sectional study on Trypanosoma cruzi was carried out in 2013 to evaluate the role of dogs as possible source of infection for humans in two rural communities of the highly endemic Bolivian Chaco (Bartolo, Chuquisaca Department, n = 57 dogs; and Ivamirapinta, Santa Cruz Department, n = 48 dogs). Giemsa-stained thick and thin smears, rapid immunochromatographic test (ICT) (Chagas Quick test, Cypress Diagnostic, Belgium) and polymerase chain reaction for T. cruzi on dried blood spots were performed. All smears proved negative by microscopic examination, whereas 23/103 (22%) were positive by ICT and 5/105 (5%) blood samples contained T. cruzi DNA, evidencing the potential role of dogs in the domestic transmission of the parasite

Development of a Cell-Based Immunodetection Assay for Simultaneous Screening of Antiviral Compounds Inhibiting Zika and Dengue Virus Replication:

Practical cell-based assays can accelerate anti-Zika (ZIKV) and anti-dengue (DENV) virus drug discovery. We developed an immunodetection assay (IA), using a pan-flaviviral monoclonal antibody recognizing a conserved envelope domain. The final protocol includes a direct virus yield reduction assay (YRA) carried out in the human Huh7 cell line, followed by transfer of the supernatant to a secondary Huh7 culture to characterize late antiviral effects. Sofosbuvir and ribavirin were used to validate the assay, while celgosivir was used to evaluate the ability to discriminate between early and late antiviral activity. In the direct YRA, at 100, 50, and 25 TCID50, sofosbuvir IC50 values were 5.0 ± 1.5, 2.7 ± 0.5, 2.5 ± 1.1 µM against ZIKV and 16.6 ± 2.8, 4.6 ± 1.4, 2.6 ± 2.2 µM against DENV; ribavirin IC50 values were 6.8 ± 4.0, 3.8 ± 0.6, 4.5 ± 1.4 µM against ZIKV and 17.3 ± 4.6, 7.6 ± 1.2, 4.1 ± 2.3 µM against DENV. Sofosbuvir and ribavirin IC50 values determined in the secondary YRA were reproducible and comparable with those obtained by direct YRA and plaque reduction assay (PRA). In agreement with the proposed mechanism of late action, celgosivir was active against DENV only in the secondary YRA (IC50 11.0 ± 1.0 µM) and in PRA (IC50 10.1 ± 1.1 µM). The assay format overcomes relevant limitations of the gold standard PRA, allowing concurrent analysis of candidate antiviral compounds against different viruses and providing preliminary information about early versus late antiviral activity

Persistence of Trypanosoma cruzi vector-borne transmission among school-age children in the Bolivian Chaco documented by 24-month longitudinal serosurveillance

Background Chagas disease represents a major public health concern in several Latin American countries, including Bolivia. Methods We present a longitudinal serosurvey for Trypanosoma cruzi antibodies among a cohort of 120 school-age children from rural communities in the Bolivian Chaco at three time points between 2017 and 2019. Serum samples extracted from dry blood spots collected on filter paper were tested for T. cruzi antibodies by enzyme-linked immunosorbent assay and rapid diagnostic test. Results T. cruzi antibodies were detected in 7/120 (5.8%), 8/120 (6.7%) and 11/120 (9.2%) samples in 2017, 2018 and 2019, respectively. An average incidence of 1.76 per 100 person-years was observed. Conclusions Our findings support the persistence of vector-borne T. cruzi transmission in this area, highlighting the need for strengthening multidisciplinary efforts against Chagas disease

LIOFeron®TB/LTBI: A novel and reliable test for LTBI and tuberculosis

Objectives: High accuracy diagnostic screening tests for tuberculosis (TB) are required to improve the diagnosis of both active TB and latent Mycobacterium tuberculosis (MTB) infection (LTBI). The novel IGRA LIOFeron®TB/LTBI assay was tested and its accuracy was compared to the QuantiFERON®-TB Gold Plus assay. Methods: A total of 389 subjects were enrolled in two cohorts and classified as healthy, active TB or LTBI persons. The blood of all the patients was tested with LIOFeron®TB/LTBI assay, containing MTB alanine dehydrogenase, able to differentiate active TB from LTBI diagnosis. The results obtained with both IGRAs, performed on the same 250 samples, were finally compared. Results: The two assays demonstrated an excellent concordance of their results with patients' diagnosis of MTB infection. ROC analysis for QuantiFERON®-TB Gold Plus showed sensitivity and specificity respectively of 98% and 97% in diagnosing active TB patients and 85% and 94% in diagnosing LTBI subjects. LIOFeron®TB/LTBI assay showed sensitivity and specificity respectively of 90% and 98% in diagnosing active TB patients and 94% and 97% in diagnosing LTBI subjects. Conclusions: The two IGRAs displayed the same high accuracy in diagnosing MTB infection/TB disease, and LIOFeron®TB/LTBI assay demonstrated higher sensitivity than QuantiFERON®-TB Gold Plus test in LTBI detection. Keywords: Mycobacterium tuberculosis, Tuberculosis diagnosis, IGRA, Alanine dehydrogenas

Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients

Low in‑hospital mortality rate in patients with COVID‑19 receiving thromboprophylaxis: data from the multicentre observational START‑COVID Register

Abstract COVID-19 infection causes respiratory pathology with severe interstitial pneumonia and extra-pulmonary complications; in particular, it may predispose to thromboembolic disease. The current guidelines recommend the use of thromboprophylaxis in patients with COVID-19, however, the optimal heparin dosage treatment is not well-established. We conducted a multicentre, Italian, retrospective, observational study on COVID-19 patients admitted to ordinary wards, to describe clinical characteristic of patients at admission, bleeding and thrombotic events occurring during hospital stay. The strategies used for thromboprophylaxis and its role on patient outcome were, also, described. 1091 patients hospitalized were included in the START-COVID-19 Register. During hospital stay, 769 (70.7%) patients were treated with antithrombotic drugs: low molecular weight heparin (the great majority enoxaparin), fondaparinux, or unfractioned heparin. These patients were more frequently affected by comorbidities, such as hypertension, atrial fibrillation, previous thromboembolism, neurological disease,and cancer with respect to patients who did not receive thromboprophylaxis. During hospital stay, 1.2% patients had a major bleeding event. All patients were treated with antithrombotic drugs; 5.4%, had venous thromboembolism [30.5% deep vein thrombosis (DVT), 66.1% pulmonary embolism (PE), and 3.4% patients had DVT + PE]. In our cohort the mortality rate was 18.3%. Heparin use was independently associated with survival in patients aged ≥ 59 years at multivariable analysis. We confirmed the high mortality rate of COVID-19 in hospitalized patients in ordinary wards. Treatment with antithrombotic drugs is significantly associated with a reduction of mortality rates especially in patients older than 59 years