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.

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.

Hepatitis C virus infection: a challenge in the complex management of two cases of multidrug-resistant tuberculosis.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) requires lengthy use of second-line drugs, burdened by many side effects. Hepatitis C virus (HCV) chronic infection increases risk of drug-induced liver injury (DILI) in these patients. Data on MDR-TB patients with concurrent HCV chronic infection treated at the same time with second-line antitubercular drugs and new direct-acting antivirals (DAAs) are lacking. We evaluate if treating at the same time HCV infection and pulmonary MDR-TB is feasible and effective. CASES PRESENTATION: In this study, we described two cases of patients with pulmonary MDR-TB and concurrent HCV chronic infection cured with DAAs at a Tertiary Infectious Diseases Hospital in Italy. During antitubercular treatment, both patients experienced a DILI before treating HCV infection. After DAAs liver enzymes normalized and HCV RNA was undetectable. Then antitubercular regimen was started according to the institutional protocol, drawn up following WHO MDR-TB guidelines. It was completed without further liver side effects and patients were declared cured from both HCV infection and MDR-TB. CONCLUSIONS: We suggest to consider treatment of chronic hepatitis C with DAAs as a useful intervention for reintroduction of second-line antitubercular agents in those patients who developed DILI, reducing the risk of treatment interruption when re-exposed to these drugs.

Unexpected human cases of cutaneous anthrax in Latium region, Italy, August 2017: integrated human-animal investigation of epidemiological, clinical, microbiological and ecological factors.

On 31 August, a veterinarian and a farmworker were hospitalised for skin lesions. Both had been exposed to a dead cow on 19 August on a farm near Rome, where eight further cattle died of confirmed anthrax later the same month. At admission, the first case showed a black depressed eschar and another smaller lesion on one hand. The second case presented deep infection of the skin, with involvement of both arms. Anthrax diagnosis was confirmed by detection of B. anthracis DNA in eschar fragments from both patients. T-cell specific immunity was studied by flow cytometry and Elispot assay after stimulation with B. anthracis secretome in blood samples collected from Case 1. Immunoglobulin production was detected by complement fixation assay. In Case 1, specific CD4+ T-cell activation was detected, without antibody production. Specific antibodies were detected only in the second patient with severe cutaneous illness. Both patients recovered. The two human anthrax cases were epidemiologically linked, but anthrax was not suspected at admission in either case. The veterinarian had initially unrecognised professional exposure and the exposed farmworker did initially not report exposure to affected animals. A One Health strategy integrating human and animal investigations was essential to confirm the diagnosis.

Recovery from Triple Infection with SARS-CoV-2, RSV and Influenza virus: A case report.

The overall probability of infection with RSV, influenza virus, or SARS-CoV-2 in the general population is assessed as high by the ECDC. A high level of respiratory virus circulation increases hospitalizations and places significant pressure on healthcare systems. Here we describe the case of a 52-year-old woman who recovered from pneumonia with a triple infection with SARS-CoV-2, RSV, and Influenza virus. We suggest searching for antigenic or molecular detection of VSR and influenza viruses, together with SARS-CoV-2, in patients with respiratory symptoms during this epidemic period, whereas all three viruses are present right now.

Utility of Liver Biopsy in the Diagnosis and Management of Possible Drug-Induced Liver Injury in Patients Receiving Antituberculosis Therapy: A Retrospective Study.

BACKGROUND: Drug-induced liver injury (DILI) secondary to ATT treatment (TB-DILI) is reported in 2-28% of patients. We present here a series of clinical cases of suspected DILI arising during antituberculosis treatment, studied with the aid of liver biopsy. METHODS: this was a retrospective descriptive study including 10 tuberculosis patients who underwent liver biopsy for suspected TB-DILI at the "Lazzaro Spallanzani" Institute from 2017 to 2022. RESULTS: Ten patients who underwent LB were extracted from the database and included in the retrospective study cohort. According to the clinical classification, eight patients had hepatocellular liver injury, one patient had cholestatic injury, and another had mixed-type injury. Histopathological diagnosis revealed liver damage due to DILI in 5/10 (50%) cases. In one case, liver biopsy showed necrotizing granulomatous hepatitis. CONCLUSIONS: Severe and persistent elevation of hepatic transaminases, hepatic cholestasis despite discontinuation of therapy, and other suspected hepatic conditions are indications for liver biopsy, which remains a valuable tool in the evaluation of selected tuberculosis patients with suspected DILI for many reasons. However, the decision to perform a liver biopsy should be based on clinical judgment, considering the benefits and risks of the procedure.

Diagnosis of Tuberculosis in a Case of Chronic Urticaria following Omalizumab Therapy.

In Italy, tuberculosis (TB) incidence in the last decade has remained constant at under 10 cases/100,000 inhabitants. In the Philippines, TB annual incidence is greater than 500 cases/100,000 inhabitants. Omalizumab is a humanized anti-IgE monoclonal antibody approved for the treatment of chronic spontaneous urticaria. We report the case of a 32-year-old Filipino woman who suffered from chronic urticaria, treated with topic steroids since June 2022 and systemic steroids for 2 weeks. In November 2022, she started omalizumab therapy at a monthly dose of 300 mg; she was not screened for TB infection. In the same month, a left laterocervical lymphadenopathy arose, which worsened in February 2023 (diameter: 3 cm). The patient recovered in April 2023 in INMI "Lazzaro Spallanzani" in Rome for suspected TB. Chest CT showed a "tree in bud" pattern at the upper-right pulmonary lobe. The patient tested positive for lymph node biopsy molecular tuberculosis. The patient started standard antituberculosis therapy. She discontinued omalizumab. To our knowledge, this is the second diagnosed TB case during omalizumab treatment, which suggests that attention should be paid to the known risk of TB during biotechnological treatments. Even if current guidelines do not recommend screening for TB before starting anti-IgE therapy, further data should be sought to assess the relationship between omalizumab treatment and active TB. Our experience suggests that screening for TB should be carried out in patients from highly tuberculosis-endemic countries before starting omalizumab therapy.

Dermatological manifestations during COVID-19 and histological picture: Description of two clinical cases.

It is not yet entirely clear what is the relevance of skin symptoms and what clinical implications are related to their appearance in COVID-19 patients. We describe two cases of COVID-19-associated pneumonia, which presented skin manifestations in advanced stage of illness, when nasopharyngeal swabs became negative for SARS-CoV-2. The first case presented erythematous, maculopapular lesions; the second developed petechial, vesicular and blood-encrusted lesions on the limbs. Histopathology documented perivascular lymphocytic infiltrates, with prevalent CD4+ T-cells in both patients. The research of SARS-CoV-2 in tissues with real time RT-PCR was negative. Basal keratinocytes displayed C4d deposits in one case, who developed laboratory signs indicative of a procoagulative condition at the same time as the skin rash. Skin manifestations during SARS-CoV-2 infection seem to be clinically relevant and further studies are necessary to assess if they are linked to systemic complications, lack of viral clearance or cascades of immune responses induced by the virus, even in patients affected by mild pneumonia.

Active Pulmonary Tuberculosis in Elderly Patients: A 2016-2019 Retrospective Analysis from an Italian Referral Hospital.

Tuberculosis (TB) in the elderly (>65 years old) has increasingly become a global health problem. It has long been recognized that older people are vulnerable to developing tuberculosis. We retrospectively evaluated data from patients older than 65 years diagnosed with pulmonary TB admitted to the National Institute for Infectious Diseases L. Spallanzani, Rome, Italy, from 1 January 2016 to 31 December 2019. One hundred and six consecutive patients were diagnosed with pulmonary TB and 68% reported at least one comorbidity and 44% at least one of the TB risk-factors. Out of the 26 elderly patients who reported an adverse event, having risk factors for TB (O.R. (Odds Ratios) = 1.45; 95% CI 1.12-3.65) and the presence of cavities on Chest X-rays (O.R. = 1.42; 95% CI 1.08-2.73) resulted in being more likely to be associated with adverse events in elderly patients. Having weight loss (O.R. = 1.31; 95% CI 1.08-1.55) and dyspnea (O.R. = 1.23; 95% CI 1.13-1.41) resulted in being significant predictors of unsuccessful treatment outcome in elderly patients. Older people with TB represent a vulnerable group, with high mortality rate, with a challenging diagnosis. Hospitalizations in tertiary referral hospital with clinical expertise in TB management can be useful to improve the outcome of these fragile patients.

Implementing a combined infection prevention and control with antimicrobial stewardship joint program to prevent caesarean section surgical site infections and antimicrobial resistance: a Tanzanian tertiary hospital experience.

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.

Usefulness of bronchoalveolar lavage in the management of patients presenting with lung infiltrates and suspect COVID-19-associated pneumonia: A case report.

OBJECTIVE: To report a clinical case of a patient with a compatible HRCT scan and two negative SARS-CoV-2 RNA upper respiratory tract specimens but with a confirmed viral infection by BAL (19 days after symptom onset). METHODS: Revision of a patient's clinical charts with COVID-19 admitted at INMI L. Spallanzani Hospital RESULTS: Two oropharyngeal swab tests of SARS-CoV-2 by qualitative real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay were performed at admission (17 days from symptoms onset) and a day apart and were found negative. BAL fluid collected 19 days after symptoms onset was positive for SARS-CoV-2. CONCLUSION: This case highlights importance of clinical suspicion of SARS-CoV-2 infection in diagnosis and infectivity assessment. We suggest collection of BAL fluid when consecutive nasopharyngeal swabs are negative, to confirm or exclude the diagnosis of COVID-19-associated pneumonia. Healthcare workers should perform aerosol-generating procedures in an adequately ventilated room and should wear adequate PPE.

Tuberculin skin test - Outdated or still useful for Latent TB infection screening?

OBJECTIVE: To make an informed viewpoint on the usefulness of Tuberculin Skin test (TST) compared to Interferon Gamma Release Assays (IGRAs) for diagnosis of Latent TB Infection (LTBI) in different geographical settings. METHODS: We reviewed the current literature on TST compared to IGRA, including national implementation of WHO LTBI recommendations and retrospective data over the past 7 years at the National Institute for Infectious Diseases "L. Spallanzani" as indirect indicator of usage of both tests under actual programmatic conditions. RESULTS: Current national guidelines vary considerably, reflecting the uncertainty and rapidly evolving evidence about the potential use of these tests. Data from Institute "L. Spallanzani" showed IGRA concordance in TST positive subjects only in 54.74% of subjects, while there was strong concordance between two tests in TST negative subjects (93.78%). CONCLUSION: Neither IGRAs nor TST can distinguish active TB from LTBI. TST will continue to be clinically useful in low and high TB endemic areas until more accurate and predictive tests will become available. Clinical judgment remains fundamental in choosing between IGRA/TST tests and interpreting their results.

Putting in harm to cure: Drug related adverse events do not affect outcome of patients receiving treatment for multidrug-resistant Tuberculosis. Experience from a tertiary hospital in Italy.

RATIONALE: Treatment of multi-drug resistant Tuberculosis (MDR-TB) is challenging because it mostly relies on drugs with lower efficacy and greater toxicity than those used for drug-susceptible TB. OBJECTIVES: Aim of the study was to describe the frequency and type of adverse drug reactions in a cohort of MDR-TB patients and their potential impact on treatment outcome. METHODS: We conducted a retrospective study in a cohort of MDR-TB patients enrolled at a tertiary referral hospital in Italy from January 2008 to December 2016. The records of patients were reviewed for epidemiological, clinical, microbiological and adverse drug reactions data. RESULTS: Seventy-four MDR-TB patients (mean age 32 years, 58.1% males, 2 XDR, 12 pre-XDR TB) were extracted from the Institute data base and included in the retrospective study cohort in the evaluation period (January 2008-December 2016). Median length of treatment duration was 20 months (IQR 14-24). Treatment outcome was successful in 57 patients (77%; 51 cured, 6 treatment completed); one patient died and one failed (2.7% overall); 15 patients were lost to follow-up (20.3%). Sixty-six (89.2%) presented adverse drug reactions during the whole treatment period. Total number of adverse drug reactions registered was 409. Three hundred forty-six (84.6%) were classified as adverse events (AEs) and 63 (15.4%) were serious AEs (SAEs). One third of the total adverse drug reactions (134/409; 32.8%) was of gastrointestinal origin, followed by 47/409 (11.5%) ototoxic drug reactions, thirty-five (8.6%) regarded central nervous system and 33 (8.1%) affected the liver. All 63 SAEs required treatment suspension with 61 SAEs out of 63 (96.8%) occurring during the first six months of treatment. Factors associated with unsuccessful treatment outcome were smoking (p = 0.039), alcohol abuse (p = 0.005) and homeless condition (p = 0.044). Neither the number of antitubercular drugs used in different combinations nor the number of AEs showed significant impact on outcome. Patients who completed the treatment experienced a greater number of AEs and SAEs (p < 0.001) if compared to lost to follow-up patients. CONCLUSIONS: Our data demonstrate that, despite the high frequency of adverse drug reactions and long term therapy, the clinical management of MDR-TB patients in a referral center could reach successful treatment according to WHO target, by implementing active and systematic clinical and laboratory assessment to detect, report and manage suspected and confirmed adverse drug reactions.

Reliability and validity of using telephone calls for post-discharge surveillance of surgical site infection following caesarean section at a tertiary hospital in Tanzania.

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.

Febrile rhabdomyolysis of unknown origin in refugees coming from West Africa through the Mediterranean.

OBJECTIVES: Cases of undiagnosed severe febrile rhabdomyolysis in refugees coming from West Africa, mainly from Nigeria, has been observed since May 2014. The aim of this study was to describe this phenomenon. METHODS: This was a multicentre retrospective observational study of cases of febrile rhabdomyolysis reported from May 2014 to December 2016 in 12 Italian centres. RESULTS: A total of 48 cases were observed, mainly in young males. The mean time interval between the day of departure from Libya and symptom onset was 26.2 days. An average 8.3 further days elapsed before medical care was sought. All patients were hospitalized with fever and very intense muscle aches. Creatine phosphokinase, aspartate aminotransferase, and lactate dehydrogenase values were abnormal in all cases. The rhabdomyolysis was ascribed to an infective agent in 16 (33.3%) cases. In the remaining cases, the aetiology was undefined. Four out of seven patients tested had sickle cell trait. No alcohol abuse or drug intake was reported, apart from a single reported case of khat ingestion. CONCLUSIONS: The long incubation period does not support a mechanical cause of rhabdomyolysis. Furthermore, viral infections such as those caused by coxsackievirus are rarely associated with such a severe clinical presentation. It is hypothesized that other predisposing conditions like genetic factors, unknown infections, or unreported non-conventional remedies may be involved. Targeted surveillance of rhabdomyolysis cases is warranted.