Francesco Castelli

Background: Effective screening for tuberculosis infection (TBI) among asylum seekers (AS) is crucial for tuberculosis (TB) elimination in low incidence countries. Methods: We assessed the proportion of completion of the screening for TBI among asylum seekers with a centralized delivery method compared to the decentralized model previously adopted in the study area (historical control). In the historical model (January 2017 to May 2018) screening of AS was performed at the arrival offering TBI testing (TST followed by IGRA among those positive), radiological investigation, treatment initiation and hospital referral, if needed, at three sites: migrant health clinic, pneumology clinic and infectious diseases department for active disease (decentralized model). In the study model (June 2018, centralized) all steps of screening were performed at a single site, at a minimum of 6 months after arrival. Multivariable Poisson regression analysis, with robust variance, was used to assess vari...

BackgroundToxicity and other drug adherence-related factors have contributed to decreased compliance to antiretroviral regimens amongst HIV-infected patients. Irregular therapy disruption causes loss of CD4 T cells, onset of drug resistance and rapid rebound of plasma viral load (VL). However, an appropriate choice of drugs and properly scheduled structured treatment interruptions (STIs) may limit VL rebound, maintain CD4 counts and minimize resistance.MethodsWe conducted a clinical study of STIs, RIGHT 901, involving 60 drug-naive patients with chronic HIV infection (CD4 >300, VL >10000) randomized to receive didanosine-stavudine-indinavir (IDV group) or didanosine-stavudine-hydroxyurea (HU group), for 12 weeks. Subsequently, all patients were randomized again to start STI (short induction) or to continue the therapy for an additional 24 weeks before starting STI (long induction). Both groups underwent four STI cycles and then stopped therapy as long as viraemia remained belo...

We describe the epidemiological pattern and genetic characteristics of 242 acute dengue infections imported to Europe by returning travellers from 2012 to 2014. The overall geographical pattern of imported dengue (South-east Asia > Americas > western Pacific region > Africa) remained stable compared with 1999 to 2010. We isolated the majority of dengue virus genotypes and epidemic lineages causing outbreaks and epidemics in Asia, America and Africa during the study period. Travellers acted as sentinels for four unusual dengue outbreaks (Madeira, 2012-13; Luanda, 2013; Dar es Salaam, 2014; Tokyo, 2014). We were able to characterise dengue viruses imported from regions where currently no virological surveillance data are available. Up to 36% of travellers infected with dengue while travelling returned during the acute phase of the infection (up to 7 days after symptom onset) or became symptomatic after returning to Europe, and 58% of the patients with acute dengue infection w...

This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out priority interventions required for these countries to progress first towards…

Lung cancer (LC) is the most common cancer among the non AIDS-defining malignancies in the highly active antiretroviral therapy (HAART) era. We described 23 HIV infected patients with a LC diagnosis followed in the Clinic of Tropical and Infectious Diseases of Brescia during the period of 1999–2009. All of these patients except two ( n = 21, 91.3%) were cigarette smokers and all had at least one risk factor for developing cancer of the lung, or predisposing comorbidities, such as a COPD (chronic obstructive pulmonary disease) or a previous pneumonia. The median age at LC diagnosis was 53.6 years (range 21.2–71.4 years). Adenocarcinoma and squamous cell carcinoma were diagnosed in 10 cases (43.5%) respectively. In 21 subjects (91.3%) cancer was detected at stage IV with metastases. The median survival was 5.95 months. Greater intervention focused on the cessation of smoking is necessary, as well as the implementation of closer screening policies, especially in HIV-positive subjects w...

Since the early stage of the current pandemic, digital contact tracing (DCT) through mobile phone apps, called “Immuni”, has been introduced to complement manual contact tracing in Italy. Until 31 December 2021, Immuni identified 44,880 COVID-19 cases, which corresponds to less than 1% of total COVID-19 cases reported in Italy in the same period (5,886,411). Overall, Immuni generated 143,956 notifications. Although the initial download of the Immuni app represented an early interest in the new tool, Immuni has had little adoption across the Italian population, and the recent increase in its download is likely to be related to the mandatory Green Pass certification for conducting most daily activities that can be obtained via the application. Therefore, Immuni failed as a support tool for the contact tracing system. Other European experiences seem to show similar limitations in the use of DTC, leaving open questions about its effectiveness, although in theory, contact tracing could a...

The study was designed to investigate the median duration of second antiretroviral regimens and factors associated with early discontinuation in HIV patients who switched with an undetectable viral load. We conducted a retrospective analysis of the Italian Cohort Naive Antiretrovirals Foundation Study (ICONA), which collects data throughout the country. Patients who started first antiretroviral therapy (ART) after January 1, 2008 in any center involved in this cohort and then switched to a second regimen were included in the study. Second ART failure was described as two HIV-RNA >200 copies/mL or the discontinuation of any drug. Statistical analysis was performed utilizing Kaplan-Meier curves and Cox regression model. The study population included 835 patients and the median duration of first ART regimens was 16 months with HIV-RNA undetectable for 13 months. The main causes of switch to second ART regimens were toxicity (42.5%) and simplification (37.5%). The switch mostly invol...

Imported cases of multidrug resistant Plasmodium falciparum and treatment failure with artemisinin-based regimens, although rare, have been described also in Western countries and their management is often challenging. This is also due to an inadequate knowledge and implementation of health prevention measures. A complex case of imported malaria caused by Plasmodium vivax/P. falciparum isolates in a patient who was not taking chemoprophylaxis while he was travelling in Cambodia is reported in this article. After failures of artemisinin-based and both oral and intravenous quinine-based regimens, a multidrug resistant P. falciparum was detected. The patient was successfully treated with atovaquone-proguanil. This experience highlights the importance of a careful management that should be based not only on the most up-to-date guidelines, but also on the awareness of a rapidly evolving scenario.

We investigated the association between persistent low-level viraemia, measured as viraemia copy-years (VCY), and all-cause mortality. We included 3271 HIV-infected patients who initiated their first combined ART (cART) during 1998-2012 enrolled in the multicentre Italian MASTER cohort. VCY was defined as the area under the curve of plasma viral load (pVL) and expressed in log10 copies · years/mL. VCY was evaluated from cART initiation until the end of follow-up [VCY-overall (VCY-o)], and stratified into before [VCY-early (VCY-e)] and after [VCY-late (VCY-l)] the eighth month from starting cART, and as the ratio of VCY-l to follow-up duration (VCY-l/FUD). The risk of death increased of about 40% for higher than the median levels of VCY-o and VCY-e. Compared with subjects with permanently suppressed pVL after the eighth month from starting cART, mortality increased by 70% for those with VCY-l ≥3 log10 copies·years/mL, and by about 20-fold for those with VCY-l/FUD ≥2.3 log10 copies/mL...

In this position paper, the European Society for Clinical Microbiology and Infectious Diseases, Study Group on Clinical Parasitology, summarizes main issues regarding the management of imported malaria cases. Malaria is a rare diagnosis in Europe, but it is a medical emergency. A travel history is the key to suspecting malaria and is mandatory in patients with fever. There are no specific clinical signs or symptoms of malaria although fever is seen in almost all non-immune patients. Migrants from malaria endemic areas may have few symptoms. Malaria diagnostics should be performed immediately on suspicion of malaria and the gold- standard is microscopy of Giemsa-stained thick and thin blood films. A Rapid Diagnostic Test (RDT) may be used as an initial screening tool, but does not replace urgent microscopy which should be done in parallel. Delays in microscopy, however, should not lead to delayed initiation of appropriate treatment. Patients diagnosed with malaria should usually be h...

In Italy few cases of rickettsioses have been reported in travellers and autochthonous cases are attributed predominantly to Rickettsia conorii, the agent of Mediterranean spotted fever. The purpose of this study was to investigate some epidemiological and clinical features of tick-borne spotted fever group rickettsiosis acquired abroad or in Italy. Serum specimens collected prospectively from patients with suspected rickettsioses were tested by immunofluorescence assay. A definitive diagnosis was made on the basis of positive serological test results at the WHO collaborative centre for rickettsial diseases, Marseille, France. We compared the clinical features of patients with confirmed rickettsioses and those showing typical clinical symptoms/signs without definitive diagnose. Eight of 26 patients suspected cases had confirmed rickettsioses. All patients were travellers returning from southern Africa (75% Rickettsia africae). Inoculation eschars were significantly more common in patients with confirmed rickettsioses (p = 0.004). Our study demonstrates that R. africae is the most frequent rickettsia observed in Italian travellers. Prior to receiving the laboratory results, physicians should start empirical treatment on the basis of epidemiologic data (e.g., travel history to Africa), and clinical findings compatible with rickettsioses (e.g., eschars).

The clinical manifestations of severe malaria are several and occur in different anatomical sites. Both parasite- and host-related factors contribute to the pathogenicity of the severe forms of the disease. Cytoadherence of infected red blood cells to the vascular endothelium of different organs and rosetting are unique features of malaria parasites which are likely to contribute to the vascular damage and the consequent excessive inflammatory/immune response of the host. In addition to cerebral malaria or severe anaemia, which are quite common manifestation of severe malaria, clinical evidences of thrombocytopenia, acute respiratory distress syndrome (ARDS), liver and kidney disease, are reported. In primigravidae from endemic areas, life threatening placental malaria may also be present.In the following pages, some of the pathogenetic aspects will be briefly reviewed and then data on selected and less frequent manifestation of severe malaria, such as liver or renal failure or ARDS...

We compared viroimmunologic response after real phenotype (r-PHT) versus virtual phenotype (v-PHT) in patients failing highly active antiretroviral therapy (HAART). A total of 201 patients with >2 years of exposure, more than six experienced drugs, >1000 HIV RNA copies/mL, and on stable HAART for >6 months were randomized to the r-PHT or v-PHT arm. The primary end point was the proportion of HIV plasma viral load (pVL) <400 copies/mL. Secondary end points were absolute pVL change, proportion of pVL reduction >0.5 log(10) copies/mL, and absolute CD4 cell change. In the intention-to-treat-last observation carried forward analysis, study outcomes were not significantly different between arms over 48 weeks of follow-up: 20% and 24% pVL <400 copies/mL; 58% and 61% pVL reduction…

West African Countries account for almost half of the estimated 20 000 000 international migrants in the continent. In the frame of the scaling up of HAART, our study aims to identify specific features and constraints of access to care for HIV migrant patients returning to Burkina Faso. From January 2007 to August 2011, the Nanoro District Hospital, serving a rural area in the Centre-West of Burkina Faso, followed 437 HIV/AIDS adult patients. Migrants were 139/437 (31.8 %), of whom 108/139 (77.7 %), declared they returned to Burkina Faso to seek care, because the area they migrated to did not offer specific HIV health assistance. At baseline, 113/139 (81,3 %) migrants and 181/298 (60,7 %) residents were in WHO clinical stages III or IV (p< 0.01). For every 100 patients/ year under HAART, 25.5 migrants (91.4 % of whom to foreign countries) and 5.7 Burkina residents were transferred to other centers (p<0.01). 21.8 migrants and 8.5 residents were dead or lost to follow up (p<0...

The recent increase of population movements is paral-leled by an increase in imported malaria cases in Europe, where malaria is not endemic (1,2). In Italy, migrants and foreign-born people visiting relatives represent an increasing proportion of imported malaria cases (3). Most ...

Triple-drug regimens are the gold standard for HIV therapy. Nucleos(t)ide reverse transcriptase inhibitors (NRTIs) reducing regimens are used to decrease drugs toxicity, exposure and costs. Aim of our study was to evaluate trends of biochemical and inflammatory indices in patients switching to dual therapy (DT). We included patients that a) switched to a DT from 2007 to 2015 from a tenofovir/abacavir-based triple regimen b) previously maintained a triple and c) subsequently a dual regimen for 12 months with virological suppression. We retrieved data measured at 5 points (at the switch, 6 and 12 months before and after switch). We used platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and CD4/CD8 ratio as inflammatory indices. We assessed temporal trends of viro-immunological, biochemical and inflammatory parameters. Overall, 364 and 65 patients switched from a tenofovir- and an abacavir-triple regimen, respectively. In the tenofovir-reducing group, creatinine ...

Capnocytophaga canimorsus infection was recently recognized as a zoonosis. We report the first case of fulminant septic shock in Italy caused by this pathogen. The patient, with a history of splenectomy, died at the main hospital in Brescia with a presumptive diagnosis of sepsis. PCR and sequencing on post mortem samples confirmed C. canimorsus as a causative organism. Our purpose is to alert medical professionals to the virulence of C. canimorsus in asplenic and immunocompromised patients.

Monoclonal antibodies (mAbs) have been known since the 1970s. However, their therapeutic potential in the medical field has recently emerged, with the advancement of manufacturing techniques. Initially exploited mainly in the oncology field, mAbs have become increasingly relevant in Infectious Diseases. Numerous mAbs have been developed against SARS-CoV 2 and have proven their effectiveness, especially in the management of the mild-to-moderate disease. In this review, we describe the monoclonal antibodies currently authorized for the treatment of the coronavirus disease 19 (COVID-19) and offer an insight into the clinical trials that led to their approval. We discuss the mechanisms of action and methods of administration as well as the prophylactic and therapeutic labelled indications (both in outpatient and hospital settings). Furthermore, we address the critical issues regarding mAbs, focusing on their effectiveness against the variants of concern (VoC) and their role now that a l...

The clinical presentation of COVID-19 is extremely heterogeneous, ranging from asymptomatic to severely ill patients. Thus, host genetic factors may be involved in determining disease presentation and progression. Given that carriers of single cystic fibrosis (CF)-causing variants of the CFTR gene—CF-carriers—are more susceptible to respiratory tract infections, our aim was to determine their likelihood of undergoing severe COVID-19. We implemented a cohort study of 874 individuals diagnosed with COVID-19, during the first pandemic wave in Italy. Whole exome sequencing was performed and validated CF-causing variants were identified. Forty subjects (16 females and 24 males) were found to be CF-carriers. Among mechanically ventilated patients, CF-carriers were more represented (8.7%) and they were significantly (p < 0.05) younger (mean age 51 years) compared to noncarriers (mean age 61.42 years). Furthermore, in the whole cohort, the age of male CF-carriers was lower, compared to n...

A cytokine storm, autoimmune features and dysfunctions of myeloid cells significantly contribute to severe coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Genetic background of the host seems to be partly responsible for severe phenotype and genes related to innate immune response seem critical host determinants. The C9orf72 gene has a role in vesicular trafficking, autophagy regulation and lysosome functions, is highly expressed in myeloid cells and is involved in immune functions, regulating the lysosomal degradation of mediators of innate immunity. A large non-coding hexanucleotide repeat expansion (HRE) in this gene is the main genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), both characterized by neuroinflammation and high systemic levels of proinflammatory cytokines, while HREs of intermediate length, although rare, are more frequent in autoimmune disorders. C9orf7...

Atazanavir/ritonavir concentrations change over pregnancy in HIV-positive patients; the impact of genetic variants is unknown. 20 patients were enrolled: antiretrovirals' plasma and intracellular concentrations were measured in addition to single nucleotide polymorphisms in transport affecting genes. Linear logistic regression showed that genetic variants in organic-anion-transporter-1B1 and pregnane-X-receptor encoding genes affected third trimester atazanavir exposure. In this prospective study genetic variants partially explained the observed inter-patient variability in third-trimester antiretrovirals' exposure.

The advent of highly active anti-retroviral therapy (HAART) has significantly improved the survival of human immunodeficiency virus (HIV)-infected patients transforming the HIV infection from a fatal illness into a manageable chronic disease. As the number of older HIV-infected individuals increases, several ageing-related co-morbidities including osteopenia/osteoporosis and fractures have emerged. Patients exposed to HIV infection and its treatment may develop fragility fractures with potential significant impact on quality of life and survival. However, the awareness of HIV-related skeletal fragility is still relatively low and most HIV-infected patients are not investigated for osteoporosis and treated with anti-osteoporotic drugs in daily clinical practice. This article reviews the literature data on osteoporosis and osteopenia in HIV infection, focusing on the pathophysiological, clinical and therapeutic aspects of fragility fractures.