Screening for Latent Tuberculosis Infection in People Living with HIV: TUBHIVIT Project, a Multicenter Italian Study.

BACKGROUND: The coexistence of HIV infection and latent tuberculosis infection (LTBI) presents a significant public health concern due to the increased risk of tuberculosis (TB) reactivation and progression to active disease. The multicenter observational cohort study, TUBHIVIT, conducted in Italy from 2017 to 2023, aimed to assess the prevalence of LTBI among people living with HIV (PLHIV) and their outcomes following LTBI screening and therapy initiation. METHODS: We performed a prospective study in five referral centers for HIV care in Italy. PLHIV who consented Tto participate underwent QuantiFERON-TB Gold Plus and clinical, microbiological, and radiological assessments to exclude subclinical tuberculosis, as opportune. PLHIV diagnosed with LTBI who started chemoprophylaxis were followed until the end of therapy. RESULTS: A total of 1105 PLHIV were screened for LTBI using the QuantiFERON-TB Gold Plus test, revealing a prevalence of 3.4% of positive results (38/1105). Non-Italy-born individuals exhibited a significantly higher likelihood of testing positive. Thirty-one were diagnosed with LTBI, 1 showed active subclinical TB, and 6 were lost to follow-up before discriminating between latent and active TB. Among the PLHIV diagnosed with LTBI, 83.9% (26/31) started chemoprophylaxis. Most individuals received 6-9 months of isoniazid-based therapy. Of the 26 PLHIV commencing chemoprophylaxis, 18 (69.2%) completed the therapy, while 3 discontinued it and 5 were still on treatment at the time of the analysis. Adverse events were observed in two cases, while in one case the patient refused to continue the treatment.

A Difficult Case of Ventriculitis in a 40-Year-Old Woman with Acute Myeloid Leukemia.

Ventriculitis and nosocomial meningitis caused by carbapenem-resistant Gram-negative and vancomycin-resistant Gram-positive bacteria represent a growing treatment challenge. A case of ventriculitis and bacteremia caused by carbapenem-resistant, KPC-producing Klebsiella pneumoniae and vancomycin-resistant Enterococcus faecium in a young woman with acute leukemia who was successfully treated with meropenem/vaborbactam (MVB), rifampicin, and linezolid is described in this paper. This case report emphasizes the importance of a multidisciplinary strategy, including infectious focus control, for the treatment of device-associated central nervous system (CNS) infections from multidrug-resistant bacteria. Considering the novel resistance patterns, more research on drug penetration into the central nervous system, as well as on the necessity of association therapies, is needed.

An Uncommon Case of Syphilis With Simultaneous, Different Lesions: Moth-Eaten Alopecia, Syphilitic Keratoderma, and Psoriasiform Syphilis.

Syphilis is a re-emerging disease, and an increasing number of cases are being reported in Italy and worldwide. In this report, we present a case of a male patient with secondary syphilis characterized by the heterogenicity of the lesions: hyperkeratosis, psoriasiform-like lesions, papules, macules, and patchy alopecia on the scalp. The patient had applied several topical antimicrobials and steroid medicaments and taken oral acyclovir, which yielded no relief, for a previous wrong diagnosis. At the time of his presentation to our clinic, syphilis was suspected and confirmed by serology. The administration of a single intramuscular dose of penicillin led to a full recovery in three weeks. Screening for HIV and other sexually transmitted infections returned negative. Clinicians should maintain a high index of suspicion for syphilis when encountering sexually active patients with atypical skin manifestations.

Oral Secondary Syphilis in an HIV-Positive Transgender Patient: A Case Report and Review of the Literature.

BACKGROUND: Syphilis is a worldwide sexually transmitted infection caused by Treponema pallidum. In most cases, the oral manifestations of syphilis infection are associated with cutaneous involvement. However, the present case report is noteworthy since the oral lesions are the sole clinical sign in an HIV-positive transgender patient. CASE PRESENTATIONS: We reported an uncommon case of secondary syphilis in a 37-year-old seropositive transgender male, whose diagnostic suspect was based only on oral mucosal lesions. The patient was referred to the Oral Medicine Unit for the presence of multiple undiagnosed painful oral lesions. The intraoral examination revealed the presence of white and red plaques on the right and the left buccal mucosa and several painful lesions localized on the upper and lower labial mucosa. No cutaneous lesions were observed. Considering the sexual history of the patient and clinical findings, secondary syphilis infection was suspected. The serologic analysis was conducted, and the diagnosis of syphilis was confirmed. Moreover, to exclude the presence of oral epithelial dysplasia or malignant disease, an incisional biopsy was performed. DISCUSSION: Compared to the literature data, oral lesions as lone signs of secondary syphilis infection are uncommon, especially in HIV-positive patients. Syphilis and HIV coinfection create a concerning situation as they interact synergistically, leading to an increased risk of transmission and faster disease progression. CONCLUSIONS: This case report emphasizes the importance of considering syphilis as a diagnostic possibility, even when oral lesions are the only clinical manifestations, especially in HIV-positive patients. Comprehensive evaluation, including a detailed sexual history and careful oral examination, is essential for accurate diagnosis and appropriate management in such cases.

Causes of hospitalization and predictors of in-hospital mortality among people living with HIV in Sicily-Italy between 2010 and 2021.

BACKGROUND: Despite the rising number of people living with human immunodeficiency virus (HIV), there is a lack of knowledge about the factors that lead to PLWHs being hospitalized in worldwide literature. Our study aimed to investigate PLWH admissions in Sicily (Italy) between January 2010 and September 2021 and to analyze the characteristics and risk factors for in-hospital mortality and differences between Italians and foreigners. METHODS: Data from the hospital discharge forms of all people living with HIV (PLWH) hospitalized in Sicilian hospitals were retrospectively collected. Age, sex, nationality, length of stay, acquired immunodeficiency syndrome (AIDS), and non-AIDS-related diseases were evaluated using univariate analysis according to in-hospital mortality rates. The factors associated with mortality were included in the logistic regression model. RESULTS: In total, 5281 admissions from 2726 PLWHs occurred, most of which were related to non-AIDS diseases. Approximately 20 % regarded foreign patients, mainly from Africa. Logistic regression analysis revealed an association between in-hospital mortality and some AIDS- and non-AIDS-related diseases (wasting syndrome, lymphomas, Kaposi sarcomas, progressive multifocal leukoencephalopathy, cryptococcosis, abscesses, sepsis, cardiovascular disease, nephropathy, and respiratory diseases). African patient admissions were significantly associated with tuberculosis, toxoplasmosis, Burkitt lymphoma, and hepatitis B diagnoses. CONCLUSIONS: Our study showed that most hospitalizations were related to non-AIDS-defining diseases, with differences between Italian and foreign patients, mainly from Africa.

Hemophagocytic lymphohistiocytosis secondary to histoplasmosis: A case report in a patient with AIDS and recent SARS-CoV-2 infection and minireview.

Here, we describe the case of a naïve HIV late presenter female African patient with progressive disseminated histoplasmosis and a severe life-threatening clinical picture in a non-endemic area. She had not visited Africa in the past decade. She developed a reactive hemophagocytic lymphohistiocytosis and an acute psychiatric disorder. Histoplasmosis was diagnosed after two bone marrow biopsies. Therapy with liposomal amphotericin B resulted in rapid and progressive improvements in blood examinations and clinical conditions, including the disappearance of psychiatric disorders. The characteristics of our case were compared with those of all other cases of hemophagocytic syndrome secondary to histoplasmosis in HIV-positive patients reported in PubMed. In conclusion, clinicians outside endemic areas should evaluate histoplasmosis as a cause of severe clinical picture, especially in a patient with a travel history to an endemic area, even after many years, considering the possible reactivation of latent infection.

Enterococcus hirae Mitral Valve Infectious Endocarditis: A Case Report and Review of the Literature.

Enterococcus hirae is a rare pathogen in human infections, although its incidence may be underestimated due to its difficult isolation. We describe the first known case of E. hirae infective endocarditis (IE), which involves the mitral valve alone, and the seventh E. hirae IE worldwide. Case presentation: a 62-year-old male was admitted to our department with a five-month history of intermittent fever without responding to antibiotic treatment. His medical history included mitral valve prolapse, recent pleurisy, and lumbar epidural steroid injections due to lumbar degenerative disc disease. Pre-admission transesophageal echocardiography (TEE) showed mitral valve vegetation, and Enterococcus faecium was isolated on blood cultures by MALDI-TOF VITEK MS. During hospitalization, intravenous (IV) therapy with ampicillin and ceftriaxone was initiated, and E. hirae was identified by MALDI-TOF Bruker Biotyper on three blood culture sets. A second TEE revealed mitral valve regurgitation, which worsened due to infection progression. The patient underwent mitral valve replacement with a bioprosthetic valve and had an uncomplicated postoperative course; he was discharged after six weeks of IV ampicillin and ceftriaxone treatment.

A case of syphilis associated with immune reconstitution inflammatory syndrome and review of the literature.

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) associated with syphilis has rarely been described in HIV-infected patients. Diagnosis can be challenging because it is not always possible to discern it from a recent infection or a worsening of an undiagnosed one. CASE PRESENTATION: An HIV-positive 42-year-old man with a poor compliance history of antiretroviral therapy presented at our unit and complained of ocular symptoms. Ocular syphilis diagnosis was posed after initial misdiagnosing with cytomegalovirus infection, and antiretroviral therapy compliance improved after switching to a bictegravir-based regimen. Despite intravenous (IV) penicillin, we observed an initial worsening with the appearance of new skin lesions, and IRIS syphilis was suspected. In the literature, 14 cases of IRIS syphilis are described, all regarding male patients. Seven were HIV naïve to therapy, and 7 HIV-experienced with poor therapy compliance. Basal syphilis serology was negative in ten, with subsequent seroconversion after the development of IRIS. IRIS-syphilis development was observed after a median time of 28 days from ART initiation; 10 cases were considered "unmasking-IRIS" and 4 "paradoxical-IRIS". Skin and ocular involvement were the most often reported. In most cases, it was not necessary to use a systemic steroid. A good outcome was reported in 12. CONCLUSIONS: Syphilis should be considered in differential diagnosis with other diseases associated with IRIS. A negative syphilis serology before beginning antiretroviral therapy could convey the impression that syphilis has been ruled out. Whereas a high index of suspicion should be maintained when symptoms suggestive of syphilis, such as ocular and skin manifestations, are noticed after therapy has begun.

Fever with perinasal and tongue lesions: A diagnostic challenge.

The diagnosis may be challenging, and high suspicion index should be maintained in immunosuppressed patients with unusual mucocutaneous lesions, even in non-endemic areas for mucocutaneous leishmaniasis.

Thromboembolic Events in Patients with Influenza: A Scoping Review.

INTRODUCTION: Influenza is an acute respiratory infection that usually causes a short-term and self-limiting illness. However, in high-risk populations, this can lead to several complications, with an increase in mortality. Aside from the well-known extrapulmonary complications, several studies have investigated the relationship between influenza and acute cardio and cerebrovascular events. Reviews of the thromboembolic complications associated with influenza are lacking. OBJECTIVES: the study aims to conduct a scoping review to analyze the epidemiological and clinical characteristics of patients suffering from influenza and thromboembolic complications. MATERIALS AND METHODS: A computerized search of historical published cases using PubMed and the terms "influenza" or "flu" and "thrombosis", "embolism", "thromboembolism", "stroke", or "infarct" for the last twenty-five years was conducted. Only articles reporting detailed data on patients with thromboembolic complications of laboratory-confirmed influenza were considered eligible for inclusion in the scoping review. RESULTS: Fifty-eight cases with laboratory documented influenza A or B and a related intravascular thrombosis were retrieved. Their characteristics were analyzed along with those of a patient who motivated our search. The localizations of thromboembolic events were pulmonary embolism 21/58 (36.2%), DVT 12/58 (20.6%), DVT and pulmonary embolism 3/58 (5.1%), acute ischemic stroke 11/58 (18.9%), arterial thrombosis 4/58 (6.8%), and acute myocardial infarction 5/58 (8.6%). DISCUSSION: Our findings are important in clarifying which thromboembolic complications are more frequent in adults and children with influenza. Symptoms of pulmonary embolism and influenza can be very similar, so a careful clinical evaluation is required for proper patient management, possible instrumental deepening, and appropriate pharmacological interventions, especially for patients with respiratory failure.

Rickettsiales in Italy.

There is no updated information on the spread of Rickettsiales in Italy. The purpose of our study is to take stock of the situation on Rickettsiales in Italy by focusing attention on the species identified by molecular methods in humans, in bloodsucking arthropods that could potentially attack humans, and in animals, possible hosts of these Rickettsiales. A computerized search without language restriction was conducted using PubMed updated as of December 31, 2020. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was followed. Overall, 36 species of microorganisms belonging to Rickettsiales were found. The only species identified in human tissues were Anaplasma phagocytophilum,Rickettsia conorii, R. conorii subsp. israelensis, R. monacensis, R. massiliae, and R. slovaca. Microorganisms transmissible by bloodsucking arthropods could cause humans pathologies not yet well characterized. It should become routine to study the pathogens present in ticks that have bitten a man and at the same time that molecular studies for the search for Rickettsiales can be performed routinely in people who have suffered bites from bloodsucking arthropods.

Direct-acting antivirals and visceral leishmaniasis: a case report.

BACKGROUND: Visceral leishmaniasis is a vector-borne parasitic disease caused by protozoa belonging to the genus Leishmania. The clinical presentation of visceral leishmaniasis strictly depends on the host immunocompetency, whereas depressive conditions of the immune system impair the capability to resolve the infection and allow reactivation from sites of latency of the parasite. CASE PRESENTATION: We describe a case of visceral leishmaniasis (VL) that occurred in a patient with chronic hepatitis C treated with direct-acting antiviral drugs (DAA). The hypothesized mechanism is the alteration of protective inflammation mechanisms secondary to DAA therapy. Downregulation of type II and III IFNs, their receptors, which accompany HCV clearance achieved during treatment with sofosbuvir and ribavirin might have a negative impact on a risk for reactivation of a previous Leishmania infection. We know indeed that IFN-γ is important to enhance killing mechanisms in macrophages, which are the primary target cells of Leishmania. CONCLUSION: Since VL is endemic in Sicily as well as in other countries of the Mediterranean basin, physicians should be aware of the possible unmasking of cryptic Leishmania infection by DAAs.

Suboptimal performance of APRI and FIB-4 in ruling out significant fibrosis and confirming cirrhosis in HIV/HCV co-infected and HCV mono-infected patients.

PURPOSE: We aimed to assess the diagnostic reliability of two indirect biomarkers, APRI and FIB-4, for the staging of liver fibrosis using transient elastography (TE) as reference standard, among HIV/HCV co-infected and HCV mono-infected patients. METHODS: This is an observational, retrospective study on subjects who had access to the RESIST HCV from October 2013 to December 2016, a regional network encompassing 22 hospitals and academic centers throughout Sicily. Sensitivity, specificity and diagnostic accuracy of indirect biomarkers for liver stiffness measurement (LSM) < 9.5 kPa (significant fibrosis) and LSM ≥ 12.5 kPa (cirrhosis) were determined by receiver operator characteristics (ROC) curves. RESULTS: 238 HIV/HCV co-infected and 1937 HCV mono-infected patients were included. Performances of FIB-4 and APRI for the detection of significant fibrosis and cirrhosis proved to be unsatisfactory, with very high false negative and false positive rates among both cohorts. No significant differences were found after stratification of HIV/HCV co-infected patients for BMI < or ≥ 25, ALT < or ≥ 40 IU/L, ALT < or ≥ 80 IU/L, and presence/absence of a bright liver echo pattern on ultrasonography. CONCLUSIONS: Differently from other studies, we detected the unreliability of APRI and FIB-4 for the assessment of liver fibrosis in both HCV mono-infected and HIV/HCV co-infected patients.

Trombiculiasis: an underreported ectoparasitosis in Sicily.

Trombiculiasis is a common but underreported ectoparasitosis characterized by an infestation of the skin by the larval stage of various species of mites belonging to the phylum Arthropoda, class Arachnida, subclass Acarina. Clinical manifestations consist of pruritic erythematous and urticarial macules and papules located on covered thin and glabrous skin. In recent studies Neotrombicula autumnalis larvae have been described as the possible vectors of pathogens such as Borrelia burgdorferi and Anaplasma phagocytophilum. Few reports of trombiculosis have been collected in the medical literature to date. We report a typical case of trombiculosis induced by trombiculid larvae of N. autumnalis, which are habitual parasites of various endo- and ectothermic vertebrates.

[Role of combination NK/KIRs in the natural history of viral infections.] / Ruolo dell'interazione NK/KIR nella storia naturale delle infezioni virali.

Immunological mechanisms involved in the genesis of the immune response against viral infections take into account the activation of both innate adaptative response. Innate immune defenses trigger a rapid local response, which is often sufficient to control viral infection, and promotes the subsequent activation of specific immune defenses. Natural killer (NK) cells that constitute a subpopulation of lymphocyte-related cells are a key factor of innate immune response and play a role in defense against viral infections by killing infected cells or by producing cytokines and interacting with adaptative immune system's cells. Killer immunoglobulin-like receptors (KIRs) regulate the activation of NK cells through their interaction with human leukocyte antigens (HLA). KIRs and HLA loci are highly polymorphic and certain HLA-KIRs combinations have been found to protect against viral infections. In this study we review how the KIRs/HLA repertoire may influence the course of hepatitis B virus (HBV), hepatitis C virus (HCV), cytomegalovirus (CMV) and Herpes Simplex Virus 1 (HSV-1) infection. Results of our study suggest that a combination of KIRs/HLA gene/alleles is able to predict the outcome of viral infection and allows to plan successful customized therapeutic strategies.

Israeli Spotted Fever in Sicily. Description of two cases and minireview.

Mediterranean spotted fever (MSF) is endemic in Italy, where Rickettsia conorii subsp. conorii was thought to be the only pathogenic rickettsia and Rhipicephalus sanguineus the vector and main reservoir. R. conorii subsp. israelensis, which belongs to the R. conorii complex, is the agent of Israeli spotted fever (ISF); apart from Israel, it has also been found in Italy (Sicily and Sardinia) and in different regions of Portugal. We describe here two severe cases of ISF which occurred in otherwise healthy Italian adults. Their characteristics are analyzed and discussed in the light of other 91 cases found through a systematic review of international literature.