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Abstract Background Liver disease is the second cause of death among HIV patients receiving highly active antiretroviral therapy (HAART) in Europe. HIV patients have a high prevalence of chronic HBV (6–10%) and HCV (33%) co-infection, and accelerated progression of viral hepatitis. Furthermore, the long duration of both HIV and HCV diseases in the HAART era increases the risk of hepatocellular carcinoma. Findings We report the case of a 49 year -old HIV/HCV co-infected male patient who developed hepatocellular carcinoma. The patient underwent a partial hepatectomy, and a few months later was treated with transcatheter arterial chemoembolisation due to hepatocarcinoma recurrence. Two months later, advanced hepatocellular carcinoma was diagnosed and sorafenib therapy was initiated. The patient achieved partial response of the main lesions, complete regression of the smallest lesions and did not experience clinical progression during the 20-month follow-up period. During therapy with sorafenib, the patient was treated with HAART with good viral and immunological responses. We used the therapeutic drug monitoring to assess antiretroviral concentrations during co-administration of sorafenib. Fosamprenavir Ctrough was found under the minimum level recommended by international guidelines. No grade 3 or 4 toxicities were observed. At month 20 of treatment, new liver lesions with portal vein thrombosis were diagnosed. After 28 months of sorafenib therapy, the patient deceased for severe liver insufficiency. Conclusions Sorafenib monotherapy demonstrated a marked delay in HCC disease progression in an HIV/HCV co-infected patient. Fosamprenavir Ctrough was found under the minimum level recommended by international guidelines, suggesting a possible interaction.

Abstract Intravenous (i.v.) artesunate is now the recommended first-line treatment of severe falciparum malaria in adults and children by WHO guidelines. Nevertheless, several cases of haemolytic anaemia due to i.v. artesunate treatment have been reported. This paper describes the case of an HIV-infected patient with severe falciparum malaria who was diagnosed with haemolytic anaemia after treatment with oral artemether-lumefantrine. The patient presented with fever, headache, and arthromyalgia after returning from Central African Republic where he had been working. The blood examination revealed acute renal failure, thrombocytopaenia and hypoxia. Blood for malaria parasites indicated hyperparasitaemia (6%) and Plasmodium falciparum infection was confirmed by nested-PCR. Severe malaria according to the laboratory WHO criteria was diagnosed. A treatment with quinine and doxycycline for the first 12 hours was initially administered, followed by arthemeter/lumefantrine (Riamet®) for a further three days. At day 10, a diagnosis of severe haemolytic anaemia was made (Hb 6.9 g/dl, LDH 2071 U/l). Hereditary and autoimmune disorders and other infections were excluded through bone marrow aspiration, total body TC scan and a wide panel of molecular and serologic assays. The patient was treated by transfusion of six units of packed blood red cell. He was discharged after complete remission at day 25. At present, the patient is in a good clinical condition and there is no evidence of haemolytic anaemia recurrence. This is the first report of haemolytic anaemia probably associated with oral artemether/lumefantrine. Further research is warranted to better define the adverse events occurring during combination therapy with artemisinin derivatives.

Abstract Introduction Prosthetic joint infection due to Mycobacterium tuberculosis is occasionally encountered in clinical practice. To the best of our knowledge, this is the first report of a prosthetic joint infection due to Mycobacterium tuberculosis complicated by psoas abscesses and secondary Addison disease. Case presentation A 67-year-old immunocompetent Caucasian woman underwent total left hip arthroplasty because of osteoarthritis. After 18 months, she underwent arthroplasty revision for a possible prosthetic infection. Periprosthetic tissue specimens for bacteria were negative, and empirical antibiotic therapy was unsuccessful. She was then admitted to our department because of complications arising 22 months after arthroplasty. A physical examination revealed a sinus tract overlying her left hip and skin and mucosal pigmentation. Her levels of C-reactive protein, basal cortisol, adrenocorticotropic hormone, and sodium were out of normal range. Results of the tuberculin skin test and QuantiFERON-TB Gold test were positive. Computed tomography revealed a periprosthetic abscess and the inclusion of the left psoas muscle. Results of microbiological tests were negative, but polymerase chain reaction of a specimen taken from the hip fistula was positive for Mycobacterium tuberculosis. Our patient's condition was diagnosed as prosthetic joint infection and muscle psoas abscess due to Mycobacterium tuberculosis and secondary Addison disease. She underwent standard treatment with rifampicin, ethambutol, isoniazid, and pyrazinamide associated with hydrocortisone and fludrocortisone. At 15 months from the beginning of therapy, she was in good clinical condition and free of symptoms. Conclusions Prosthetic joint infection with Mycobacterium tuberculosis is uncommon. A differential diagnosis of tuberculosis should be considered when dealing with prosthetic joint infection, especially when repeated smears and histology examination from infected joints are negative. Clinical outcomes of prosthetic joint infection by Mycobacterium tuberculosis are unpredictable, especially given the limited literature in this field and the uncertainty of whether medical treatment alone can eradicate the infection without prosthesis removal. Furthermore, this case report raises interesting issues such as the necessity of a follow-up evaluation after treatment based on clinical conditions, the utility of a more standardized length of treatment for periprosthetic tuberculous infection, and the importance of a high diffusion capacity of anti-mycobacterial agents in order to eradicate the infection.

Background: The long-term effects of COVID-19, which can vary significantly in type and timing, are considered relevant and impacting on the well-being of individuals. The present study aims to assess the incidence of outpatient care in the post-acute phase of SARS-CoV-2 infection in two Italian regions., Methods: The study has a multicentre, population-based, pre-post, repeated measures design to compare the incidence rate of access to outpatient visits and diagnostics before and after SARS-CoV-2 infection, considering a follow-up of 24 months. The study made use of previously recorded large-scale healthcare data available in the administrative databases of the Emilia-Romagna (E-R) and Veneto regions. Analyses were carried out separately in the two regions and results were pooled using random effects meta-analysis., Results: There were 27,140 subjects in E-R and 22,876 in Veneto who were included in the analysis. The pooled outputs showed an increase in rates of outpatient visits and diagnostics starting from month 2 after SARS-CoV-2 infection (IRR = 1.68, 95% CI = 1.56-1.81) with a peak at month 4 (IRR = 2.05, 95% CI = 1.95-2.15); the increase continued with reduced intensity up to month 15. Stratified analysis revealed that subjects with severe acute COVID-19 had a higher increase in rates (up to IRR = 3.96, 95% CI = 2.89-5.44), as well as patients with no comorbidities (up to IRR = 2.71, 95% CI = 2.60-2.83)., Conclusion: Long-term effects of COVID-19 include an increase in the healthcare burden especially in the first months after the acute infection. The increased demand for resources can last up to two years after infection in particular subgroups of patients such as subjects admitted to hospital during the acute phase due to the severe presentation of the disease., Competing Interests: Declarations. Ethics approval and consent to participate: This study involving human participants was reviewed and approved by Comitato Etico Area Vasta Emilia Nord (on 8-th February 2022), Comitato Etico Area Vasta Emilia Centro (on 19-th January 2022), and Comitato Etico della Romagna (on 18-th February 2022) for the E-R cohort, and by Comitato Etico per la Sperimentazione Clinica delle Province di Verona e Rovigo (on 21-st July 2021) for the Veneto Cohort. Written informed consent was not provided because this study was considered an exemption to Art. 14 of the General Data Protection Regulation (GDPR), due to the disproportionate effort to provide the information to data subjects about the existence of the study processing operation and that personal (health) data were processed for scientific purposes. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Several studies reported alterations of the human gut microbiota (GM) during COVID-19. To evaluate the potential role of the GM as an early predictor of COVID-19 at disease onset, we analyzed gut microbial samples of 315 COVID-19 patients that differed in disease severity. We observed significant variations in microbial diversity and composition associated with increasing disease severity, as the reduction of short-chain fatty acid producers such as Faecalibacterium and Ruminococcus , and the growth of pathobionts as Anaerococcus and Campylobacter . Notably, we developed a multi-class machine-learning classifier, specifically a convolutional neural network, which achieved an 81.5% accuracy rate in predicting COVID-19 severity based on GM composition at disease onset. This achievement highlights its potential as a valuable early biomarker during the first week of infection. These findings offer promising insights into the intricate relationship between GM and COVID-19, providing a potential tool for optimizing patient triage and streamlining healthcare during the pandemic.IMPORTANCEEfficient patient triage for COVID-19 is vital to manage healthcare resources effectively. This study underscores the potential of gut microbiota (GM) composition as an early biomarker for COVID-19 severity. By analyzing GM samples from 315 patients, significant correlations between microbial diversity and disease severity were observed. Notably, a convolutional neural network classifier was developed, achieving an 81.5% accuracy in predicting disease severity based on GM composition at disease onset. These findings suggest that GM profiling could enhance early triage processes, offering a novel approach to optimizing patient management during the pandemic., Competing Interests: The authors declare no conflict of interest.

COVID-19 pandemic brought chemosensory impairment to the forefront of medicine, revealing gaps in the knowledge of pathophysiological mechanisms, true prevalence and preventive/therapeutic alternatives. This is a sub-study of the ORCHESTRA cohort focusing on post-COVID-19 chemosensory symptoms. Risk factors for neurosensorial cluster of post-COVID-19 syndrome (NSc-PCS) were assessed through multivariable analysis. Psychophysical validated tests were applied on a sub-population of 50 patients. Qualitative chemosensory symptoms as well as nasal and oral chemesthesis were evaluated through anamnestic interview and the quality of life through the SF-36 questionnaire. Chemosensory symptoms evolution and olfactory training's outcome were assessed through phone-call interviews. Out of 1187 patients (female, N = 630), 550 (47%) presented NSc-PCS, with a lower risk for older age and monoclonal antibodies treatment, and a higher risk in females (p < 0.001). Out of the 50 patients evaluated with psychophysical tests, 66% showed smell reduction with a qualitative alteration in 50% of hyposmic and 35% of normosmic patients. Hypogeusia was present in 14 (28%) of the patients assessed, with 56% showing a qualitative alteration; 53% of normogeusic patients presented qualitative disorders. NSc-PCS has a complex, fluctuating, multifaceted presentation. Quantifying and characterizing COVID-19-related chemosensory impairment is key to understand underlying mechanisms and to develop preventive and therapeutic treatment., (© 2024. The Author(s).)

COVID-19 has been associated with having a negative impact on patients' gut microbiome during both active disease and in the post-acute phase. In acute COVID-19, rapid alteration of the gut microbiome composition was observed, showing on one side a reduction in beneficial symbionts (e.g., Roseburia , Lachnospiraceae ) and on the other side an increase in opportunistic pathogens such as Enterococcus and Proteobacteria . Alpha diversity tends to decrease, especially initially with symptom onset and hospital admission. Although clinical recovery appears to align with improved gut homeostasis, this process could take several weeks, even in mild infections. Moreover, patients with COVID-19 post-acute syndrome showed changes in gut microbiome composition, with specific signatures associated with decreased respiratory function up to 12 months following acute disease. Potential treatments, especially probiotic-based therapy, are under investigation. Open questions remain on the possibility to use gut microbiome data to predict disease progression and on potential confounders that may impair result interpretation (e.g., concomitant therapies in the acute phase; reinfection, vaccines, and occurrence of novel conditions or diseases in the post-acute syndrome). Understanding the relationships between gut microbiome dynamics and disease progression may contribute to better understanding post-COVID syndrome pathogenesis or inform personalized treatment that can affect specific targets or microbiome markers.

Background: Lack of specific definitions of clinical characteristics, disease severity, and risk and preventive factors of post-COVID-19 syndrome (PCS) severely impacts research and discovery of new preventive and therapeutics drugs., Methods: This prospective multicenter cohort study was conducted from February 2020 to June 2022 in 5 countries, enrolling SARS-CoV-2 out- and in-patients followed at 3-, 6-, and 12-month from diagnosis, with assessment of clinical and biochemical features, antibody (Ab) response, Variant of Concern (VoC), and physical and mental quality of life (QoL). Outcome of interest was identification of risk and protective factors of PCS by clinical phenotype, setting, severity of disease, treatment, and vaccination status. We used SF-36 questionnaire to assess evolution in QoL index during follow-up and unsupervised machine learning algorithms (principal component analysis, PCA) to explore symptom clusters. Severity of PCS was defined by clinical phenotype and QoL. We also used generalized linear models to analyse the impact of PCS on QoL and associated risk and preventive factors. CT registration number: NCT05097677., Findings: Among 1796 patients enrolled, 1030 (57%) suffered from at least one symptom at 12-month. PCA identified 4 clinical phenotypes: chronic fatigue-like syndrome (CFs: fatigue, headache and memory loss, 757 patients, 42%), respiratory syndrome (REs: cough and dyspnoea, 502, 23%); chronic pain syndrome (CPs: arthralgia and myalgia, 399, 22%); and neurosensorial syndrome (NSs: alteration in taste and smell, 197, 11%). Determinants of clinical phenotypes were different (all comparisons p < 0.05): being female increased risk of CPs, NSs, and CFs; chronic pulmonary diseases of REs; neurological symptoms at SARS-CoV-2 diagnosis of REs, NSs, and CFs; oxygen therapy of CFs and REs; and gastrointestinal symptoms at SARS-CoV-2 diagnosis of CFs. Early treatment of SARS-CoV-2 infection with monoclonal Ab (all clinical phenotypes), corticosteroids therapy for mild/severe cases (NSs), and SARS-CoV-2 vaccination (CPs) were less likely to be associated to PCS (all comparisons p < 0.05). Highest reduction in QoL was detected in REs and CPs (43.57 and 43.86 vs 57.32 in PCS-negative controls, p < 0.001). Female sex (p < 0.001), gastrointestinal symptoms (p = 0.034) and renal complications (p = 0.002) during the acute infection were likely to increase risk of severe PCS (QoL <50). Vaccination and early treatment with monoclonal Ab reduced the risk of severe PCS (p = 0.01 and p = 0.03, respectively)., Interpretation: Our study provides new evidence suggesting that PCS can be classified by clinical phenotypes with different impact on QoL, underlying possible different pathogenic mechanisms. We identified factors associated to each clinical phenotype and to severe PCS. These results might help in designing pathogenesis studies and in selecting high-risk patients for inclusion in therapeutic and management clinical trials., Funding: The study received funding from the Horizon 2020 ORCHESTRA project, grant 101016167; from the Netherlands Organisation for Health Research and Development (ZonMw), grant 10430012010023; from Inserm, REACTing (REsearch & ACtion emergING infectious diseases) consortium and the French Ministry of Health, grant PHRC 20-0424., Competing Interests: AT received a grant from the Netherlands Organization for Health Research and Development (ZonMw) (grant number 10430012010023). JG received funding from ViiV Healthcare, Gilead Sciences, Theratechnologies, Astra-Zeneca, and Merck, all outside this study. MG received funding for lectures at educational events from Pfizer, Shionogi, MSD, Menarini, and Gilead, all outside this study. All other authors have nothing to declare., (© 2023 The Authors.)

Introduction: Detection strategies in vulnerable populations such as people experiencing homelessness (PEH) need to be explored to promptly recognize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks. This study investigated the diagnostic accuracy of a rapid SARS-CoV-2 Ag test in PEH during two pandemic waves compared with gold standard real-time multiplex reverse transcription polymerase chain reaction (rtRT-PCR)., Methods: All PEH ≥ 18 years requesting residence at the available shelters in Verona, Italy, across two cold-weather emergency periods (November 2020-May 2021 and December 2021-April 2022) were prospectively screened for SARS-CoV-2 infection by means of a naso-pharyingeal swab. A lateral flow immunochromatographic assay (Biocredit ® COVID-19 Ag) was used as antigen-detecting rapid diagnostic test (Ag-RDT). The rtRT-PCR was performed with Allplex™ SARS-CoV-2 assay kit (Seegene). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated as measures for diagnostic accuracy., Results: Overall, 503 participants were enrolled during the two intervention periods for a total of 732 paired swabs collected: 541 swabs in the first period and 191 in the second. No significant differences in demographic and infection-related characteristics were observed in tested subjects in the study periods, except for the rate of previous infection (0.8% versus 8%; p < 0.001) and vaccination (6% versus 73%; p < 0.001). The prevalence of SARS-CoV-2 in the cohort was 8% (58/732 swabs positive with rtRT-PCR). Seventeen swabs were collected from symptomatic patients (7%). Among them, the concordance between rtRT-PCR and Ag-RDT was 100%, 7 (41.2%) positive and 10 negative pairs. The overall sensitivity of Ag-RDT was 63.8% (95% CI 60.3-67.3) and specificity was 99.8% (95% CI 99.6-100). PPV and NPV were 97.5% and 96.8%, respectively. Sensitivity and specificity did not change substantially across the two periods (65.1% and 99.8% in 2020-2021 vs. 60% and 100% in 2021-2022)., Conclusions: A periodic Ag-RDT-based screening approach for PEH at point of care could guide preventive measures, including prompt isolation, without referral to hospital-based laboratories for molecular test confirmation in case of positive detection even in individuals asymptomatic for COVID-19. This could help reduce the risk of outbreaks in shelter facilities., (© 2023. The Author(s).)

The clinical impact of anti-spike monoclonal antibodies (mAb) in Coronavirus Disease 2019 (COVID-19) breakthrough infections is unclear. We present the results of an observational prospective cohort study assessing and comparing COVID-19 progression in high-risk outpatients receiving mAb according to primary or breakthrough infection. Clinical, serological and virological predictors associated with 28-day COVID-19-related hospitalization were identified using multivariate logistic regression and summarized with odds ratio (aOR) and 95% confidence interval (CI). A total of 847 COVID-19 outpatients were included: 414 with primary and 433 with breakthrough infection. Hospitalization was observed in 42/414 (10.1%) patients with primary and 8/433 (1.8%) patients with breakthrough infection ( p < 0.001). aOR for hospitalization was significantly lower for breakthrough infection (aOR 0.12, 95%CI: 0.05-0.27, p < 0.001) and higher for immunocompromised status (aOR:2.35, 95%CI:1.08-5.08, p = 0.003), advanced age (aOR:1.06, 95%CI: 1.03-1.08, p < 0.001), and male gender (aOR:1.97, 95%CI: 1.04-3.73, p = 0.037). Among the breakthrough infection group, the median SARS-CoV-2 anti-spike IgGs was lower ( p < 0.001) in immunocompromised and elderly patients >75 years compared with that in the immunocompetent patients. Our findings suggest that, among mAb patients, those with breakthrough infection have significantly lower hospitalization risk compared with patients with primary infection. Prognostic algorithms combining clinical and immune-virological characteristics are needed to ensure appropriate and up-to-date clinical protocols targeting high-risk categories.

Background: Point-of-care tests could be essential in differentiating bacterial and viral acute community-acquired lower respiratory tract infections and driving antibiotic stewardship in the community., Objectives: To assess diagnostic test accuracy of point-of-care tests in community settings for acute community-acquired lower respiratory tract infections., Data Sources: Multiple databases (MEDLINE, EMBASE, Web of Science, Cochrane Library, Open Gray) from inception to 31 May 2021, without language restrictions., Study Eligibility Criteria: Diagnostic test accuracy studies involving patients at primary care, outpatient clinic, emergency department and long-term care facilities with a clinical suspicion of acute community-acquired lower respiratory tract infections. The comparator was any test used as a comparison to the index test. In order not to limit the study inclusion, the comparator was not defined a priori., Assessment of Risk of Bias: Four investigators independently extracted data, rated risk of bias, and assessed the quality using QUADAS-2., Methods of Data Synthesis: The measures of diagnostic test accuracy were calculated with 95% CI., Results: A total of 421 studies addressed at least one point-of-care test. The diagnostic performance of molecular tests was higher compared with that of rapid diagnostic tests for all the pathogens studied. The accuracy of stand-alone signs and symptoms or biomarkers was poor. Lung ultrasound showed high sensitivity and specificity (90% for both) for the diagnosis of bacterial pneumonia. Rapid antigen-based diagnostic tests for influenza, respiratory syncytial virus, human metapneumovirus, and Streptococcus pneumoniae had sub-optimal sensitivity (range 49%-84%) but high specificity (>80%)., Discussion: Physical examination and host biomarkers are not sufficiently reliable as stand-alone tests to differentiate between bacterial and viral pneumonia. Lung ultrasound shows higher accuracy than chest X-ray for bacterial pneumonia at emergency department. Rapid antigen-based diagnostic tests cannot be considered fully reliable because of high false-negative rates. Overall, molecular tests for all the pathogens considered were found to be the most accurate., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: A major limitation of current predictive prognostic models in patients with COVID-19 is the heterogeneity of population in terms of disease stage and duration. This study aims at identifying a panel of clinical and laboratory parameters that at day-5 of symptoms onset could predict disease progression in hospitalized patients with COVID-19., Methods: Prospective cohort study on hospitalized adult patients with COVID-19. Patient-level epidemiological, clinical, and laboratory data were collected at fixed time-points: day 5, 10, and 15 from symptoms onset. COVID-19 progression was defined as in-hospital death and/or transfer to ICU and/or respiratory failure (PaO 2 /FiO 2 ratio < 200) within day-11 of symptoms onset. Multivariate regression was performed to identify predictors of COVID-19 progression. A model assessed at day-5 of symptoms onset including male sex, age > 65 years, dyspnoea, cardiovascular disease, and at least three abnormal laboratory parameters among CRP (> 80 U/L), ALT (> 40 U/L), NLR (> 4.5), LDH (> 250 U/L), and CK (> 80 U/L) was proposed. Discrimination power was assessed by computing area under the receiver operating characteristic (AUC) values., Results: A total of 235 patients with COVID-19 were prospectively included in a 3-month period. The majority of patients were male (148, 63%) and the mean age was 71 (SD 15.9). One hundred and ninety patients (81%) suffered from at least one underlying illness, most frequently cardiovascular disease (47%), neurological/psychiatric disorders (35%), and diabetes (21%). Among them 88 (37%) experienced COVID-19 progression. The proposed model showed an AUC of 0.73 (95% CI 0.66-0.81) for predicting disease progression by day-11., Conclusion: An easy-to-use panel of laboratory/clinical parameters computed at day-5 of symptoms onset predicts, with fair discrimination ability, COVID-19 progression. Assessment of these features at day-5 of symptoms onset could facilitate clinicians' decision making. The model can also play a role as a tool to increase homogeneity of population in clinical trials on COVID-19 treatment in hospitalized patients., (© 2021. The Author(s).)

Background: Management and control of coronavirus disease 2019 (COVID-19) relies on reliable diagnostic testing., Objectives: To evaluate the diagnostic test accuracy (DTA) of nucleic acid amplification tests (NAATs) for the diagnosis of coronavirus infections., Data Sources: PubMed, Web of Science, the Cochrane Library, Embase, Open Grey and conference proceeding until May 2019. PubMed and medRxiv were updated for COVID-19 on 31st August 2020., Study Eligibility: Studies were eligible if they reported on agreement rates between different NAATs using clinical samples., Participants: Symptomatic patients with suspected upper or lower respiratory tract coronavirus infection., Methods: The new NAAT was defined as the index test and the existing NAAT as reference standard. Data were extracted independently in duplicate. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Confidence regions (CRs) surrounding summary sensitivity/specificity pooled by bivariate meta-analysis are reported. Heterogeneity was assessed using meta-regression., Results: Fifty-one studies were included, 22 of which included 10 181 persons before COVID-19 and 29 including 8742 persons diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The overall summary sensitivity was 89.1% (95%CR 84.0-92.7%) and specificity 98.9% (95%CR 98.0-99.4%). Nearly all the studies evaluated different PCRs as both index and reference standards. Real-time RT PCR assays resulted in significantly higher sensitivity than other tests. Reference standards at high risk of bias possibly exaggerated specificity. The pooled sensitivity and specificity of studies evaluating SARS-COV-2 were 90.4% (95%CR 83.7-94.5%) and 98.1% (95%CR 95.9-99.2), respectively. SARS-COV-2 studies using samples from the lower respiratory tract, real-time RT-PCR, and tests targeting the N or S gene or more than one gene showed higher sensitivity, and assays based on reverse transcriptase loop-mediated isothermal amplification (RT-LAMP), especially when targeting only the RNA-dependent RNA polymerase (RdRp) gene, showed significantly lower sensitivity compared to other studies., Conclusions: Pooling all studies to date shows that on average 10% of patients with coronavirus infections might be missed with PCR tests. Variables affecting sensitivity and specificity can be used for test selection and development., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Surgical site infections are a leading cause of morbidity and mortality after caesarean section, especially in Low and Middle Income Countries. We hypothesized that a combined infection prevention and control with antimicrobial stewardship joint program would decrease the rate of post- caesarean section surgical site infections at the Obstetrics & Gynaecology Department of a Tanzanian tertiary hospital., Methods: The intervention included: 1. formal and on-job trainings on infection prevention and control; 2. evidence-based education on antimicrobial resistance and good antimicrobial prescribing practice. A second survey was performed to determine the impact of the intervention. The primary outcome of the study was post-caesarean section surgical site infections prevalence and secondary outcome the determinant factors of surgical site infections before/after the intervention and overall. The microbiological characteristics and patterns of antimicrobial resistance were ascertained., Results: Total 464 and 573 women were surveyed before and after the intervention, respectively. After the intervention, the antibiotic prophylaxis was administered to a significantly higher number of patients (98% vs 2%, p < 0.001), caesarean sections were performed by more qualified operators (40% vs 28%, p = 0.001), with higher rates of Pfannenstiel skin incisions (29% vs 18%, p < 0.001) and of absorbable continuous intradermic sutures (30% vs 19%, p < 0.001). The total number of post-caesarean section surgical site infections was 225 (48%) in the pre-intervention and 95 (17%) in the post intervention group (p < 0.001). A low prevalence of gram-positive isolates and of methicillin-resistant Staphylococus aureus was detected in the post-intervention survey., Conclusions: Further researches are needed to better understand the potential of a hospital-based multidisciplinary approach to surgical site infections and antimicrobial resistance prevention in resource-constrained settings.

The vast majority of rabies deaths occur in developing countries and rural areas. Due to the absence of surveillance and the lack of reliable information, many endemic countries are not able to assess their rabies burden and implement appropriate solutions. This study reports the incidence of animal bites considered at risk of rabies transmission, along with rates and determinants of the adherence to post-exposure prophylaxis (PEP) between 2008 and 2014 in Dodoma Region, Tanzania. A retrospective analysis of rabid animal bites considered at risk of rabies transmission at Dodoma Regional Referral Hospital (DRRH) during 2008-2014 was conducted. Data were collected from the registers of patients presenting to the hospital because of a potential rabies exposure. The patients were assessed by a trained health worker and each bite was considered as "at risk of rabies" based on the victim's description of the event. Overall, 10,771 patients coming from Dodoma Region attended DRRH because of a bite from a suspected rabid animal, giving a mean incidence of 74 bites at risk of rabies transmission per 100,000 persons per year. Overall, only 46.0% of people exposed received a complete course of PEP and 61.6% attended the clinic within 48 hours after the bite. Multivariate analysis shows that people age >15 years, residence in rural areas and occurrence during the rainy season were independently associated to delayed access to care. Male gender, age below 15 years. and bites occurring during the dry season were associated with completion of PEP. In this area with a high rate of at-risk bites, several factors-mainly related to health care access and to the affordability and delivery of rabies vaccines-still need to be addressed in order to reduce gender and social inequalities in rabies prevention and control. Further efforts are required to establish an efficient rabies surveillance system in Dodoma Region., Competing Interests: The authors have declared that no competing interests exist.

P. jiroveci (Pj) causes a potentially fatal pneumonia in immunocompromised patients and the factors associated with a bad outcome are poorly understood. A retrospective analysis on Pj pneumonia (PjP) cases occurring in Tor Vergata University Hospital, Italy, during the period 2011-2015. The patients' demographic, clinical and radiological characteristics and the Pj genotypes were considered. The study population included 116 patients, 37.9% of whom had haematological malignancy or underwent haematological stem cell transplantation (HSCT), 22.4% had HIV infection, 16.4% had chronic lung diseases (CLD), 7.8% had a solid cancer, and 3.4% underwent a solid organ transplant (SOT). The remaining 12.1% had a miscellaneous other condition. At univariate analysis, being older than 60 years was significantly correlated with a severe PjP (OR [95%CI] 2.52 [0.10-5.76]; p = 0.031) and death (OR [95%CI] 2.44 [1.05-5.70]; p = 0.036), while a previous trimethoprim/sulfamethoxazole (TMP/SMX) prophylaxis were significantly associated with a less severe pneumonia (OR[95%CI] 0.35 [0.15-0.84], p = 0.023); moreover, death due to PjP was significantly more frequent in patients with CLD (OR[95%CI] 3.26 [1.17-9.05]; p = 0.019) while, admission to the Infectious Diseases Unit was significantly associated with fewer deaths (OR[95%CI] 0.10 [0.03-0.36], p = 0.002). At multivariate analysis, a better PjP outcome was observed in patients taking TMP/SMX prophylaxis and that were admitted to the Infectious Diseases Unit (OR[95%CI] 0.27 [0.07-1.03], p = 0.055, OR[95%CI] 0.16 [0.05-0.55]; p = 0.004, respectively). In conclusion, in our study population, TMP/SMX prophylaxis and infectious disease specialist approach were variables correlated with a better PjP outcome.

Background: Surgical site infection (SSI) is a common post-operative complication causing significant morbidity and mortality. Many SSI occur after discharge from hospital. Post-discharge SSI surveillance in low and middle income countries needs to be improved., Methodology: We conducted an observational cohort study in Dodoma, Tanzania to examine the sensitivity and specificity of telephone calls to detect SSI after discharge from hospital in comparison to a gold standard of clinician review. Women undergoing caesarean section were enrolled and followed up for 30 days. Women providing a telephone number were interviewed using a structured questionnaire at approximately days 5, 12 and 28 post-surgery. Women were then invited for out-patient review by a clinician blinded to the findings of telephone interview., Results: A total of 374 women were enrolled and an overall SSI rate of 12% ( n  = 45) was observed. Three hundred and sixteen (84%) women provided a telephone number, of which 202 had at least one telephone interview followed by a clinical review within 48 h, generating a total of 484 paired observations. From the clinical reviews, 25 SSI were diagnosed, of which telephone interview had correctly identified 18 infections; telephone calls did not incorrectly identify SSI in any patients. The overall sensitivity and specificity of telephone interviews as compared to clinician evaluation was 72 and 100%, respectively., Conclusion: The use of telephone interview as a diagnostic tool for post-discharge surveillance of SSI had moderate sensitivity and high specificity in Tanzania. Telephone-based detection may be a useful method for SSI surveillance in low-income settings with high penetration of mobile telephones.

Objective: The impact of HIV-1 tropism on the emergence of non-AIDS events was evaluated in a cohort of 116 antiretroviral therapy (ART) responder patients., Methods: The patients were followed for the emergence of hypertension, renal impairment, metabolic and bone disorders (defined as non-AIDS events) each 8 weeks at standard visits. A V3 plasma sequence genotype analysis was performed at the time of ART initiation and the geno2pheno algorithm with the results that defines the false-positive rate (FPR) was used to infer HIV tropism. The associations between the non-AIDS events and the FPR at baseline were evaluated using the χ test for trend. A Cox-regression analysis using the counting process formulation of Andersen and Gill was performed to define whether the emergence of non-AIDS events was correlated to FPR., Results: The prevalence of at least one non-AIDS event resulted higher in patients with a FPR below 10% than in patients with a R5 virus (P = 0.033). Patients with a FPR below 5.0% most frequently developed non-AIDS events during ART (P = 0.01). A higher prevalence of patients with at least two AIDS events was found in the group of patients with a FPR below 5.0% with respect to the others (P < 0.001). At multivariate Cox-regression analysis, having an X4 virus and age were independently associated with a higher probability of non-AIDS event development., Conclusion: This study shows that an X4 virus, particularly a FPR less than 5%, is related to non-AIDS events development. Further studies are warranted to understand the mechanisms underlying this phenomenon.

In 2013, an estimated 1.5 million HIV-positive pregnant women gave birth, with 240,000 children worldwide acquiring HIV. More than 90% of new pediatric infections occurred in Sub-Saharan Africa. The latest WHO guidelines recommended efavirenz (EFV)-based antiretroviral therapy as the first-line regimen for prevention of mother-to-child transmission of HIV (PMTCT). On the other hand, some data suggest that nevirapine (NVP), a well-known antiretroviral, could still play a relevant role in PMTCT, especially in resource-limited settings (RLSs) where the fertility rate is dramatically high compared to developed countries. Given the lack of an unanimous consensus and definitive opinions, this paper goes through the reasons for WHO decisions and aims at refreshing the debate about NVP and EFV pros and cons for PMTCT in RLSs.

It has been shown that P-glycoprotein (P-gp) can greatly affect the cell uptake of antiretroviral drugs, thus hampering their access to HIV-1 replication sites. Lymphocytes are important sites of replication of HIV and target of other drugs, modification on these cells of P-gp could have an effect on pharmacokinetic of antiretrovirals and drug substrates. Blood samples from 16 healthy volunteers were used to determine the expression of P-gp on total, T and T helper lymphocytes after exposure to darunavir, a second generation protease inhibitor, and raltegravir, the first approved integrase inhibitor. Moreover, the effect of the drugs on P-gp functional activity was also studied by the rhodamine-123 efflux test. Darunavir, but not raltegravir, exposure caused a moderate, dose-dependent increment in P-gp expression in total, T and T helper lymphocytes, as demonstrated by the relative frequency of P-gp+ cells and by the amount of P-gp molecules present on cell surface. Functionally, incubation with darunavir led to a marked inhibition of P-gp activity measured by the efflux of rhodamine-123 similar to that observed by verapamil, a specific P-gp inhibitor. Raltegravir was not able to modify the efflux of rhodamine-123 level. Data show that darunavir, unlike raltegravir, may modify the expression and functionality of P-gp on human lymphocytes, thus leading to potential changes in intracellular concentrations of darunavir in patients treated with other drugs substrate of P-gp and vice versa. Our study highlights the need for studies on drug interactions via the P-gp modulation mechanism, especially with the current multi-drug regimens., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Anti-tumor necrosis factor alpha (anti-TNF-α) is used in the treatment of rheumatic diseases not responsive to first-line regimens. Data on the safety of anti-TNF-α in HIV-infected patients are scarce and conflicting. We describe a case of septic shock and multiorgan failure that occurred after etanercept initiation and influenza vaccination in an HIV-infected woman with rheumatoid arthritis.

Background: In recent years, Nocardia farcinica has been reported to be an increasingly frequent cause of localized and disseminated infections in the immunocompromised patient. However, recent literature is limited. We report a case of left thigh phlegmon caused by N. farcinica that occurred in a patient with leprosy undergoing treatment with prednisone for leprosy reaction., Case Presentation: We describe the case of left thigh phlegmon caused by Nocardia farcinica in a 54-year-old Italian man affected by multi-bacillary leprosy. The patient had worked in South America for 11 years. Seven months after his return to Italy, he was diagnosed with leprosy and started multi-drug antibiotic therapy plus thalidomide and steroids. Then, during therapy with rifampicin monthly, minocycline 100 mg daily, moxifloxacin 400 mg daily, and prednisone (the latter to treat type 2 leprosy reaction), the patient complained of high fever associated with erythema, swelling, and pain in the left thigh. Therefore, he was admitted to our hospital with the clinical suspicion of cellulitis. Ultrasound examination and Magnetic Resonance Imaging showed left thigh phlegmon. He was treated with drainage and antibiotic therapy (meropenem and vancomycin replaced by daptomycin). The responsible organism, Nocardia farcinica, was identified by 16S rRNA sequencing in the purulent fluid taken out by aspiration. The patient continued treatment with intravenous trimethoprim/sulfamethoxazole and imipenem followed by oral trimethoprim/sulfamethoxazole and moxifloxacin. A whole-body computed tomography did not reveal dissemination to other organs like the lung or brain.The patient was discharged after complete remission. Oral therapy with trimethoprim/sulfamethoxazole, moxifloxacin, rifampicin monthly, clofazimine and thalidomide was prescribed to be taken at home. One month after discharge from the hospital the patient is in good clinical condition with complete resolution of the phlegmon., Conclusion: N. farcinica is a rare infectious agent that mainly affects immunocompromised patients. Presentation of phlegmon only without disseminated infection is unusual, even in these kinds of patients. In any case, a higher index of suspicion is needed, as diagnosis can easily be missed due to the absence of characteristic symptoms and the several difficulties usually encountered in identifying the pathogen.