Actinomyces spp. Prosthetic Vascular Graft Infection (PVGI): A Multicenter Case-Series and Narrative Review of the Literature.

BACKGROUND: Actinomycosis represents a challenging and under-reported complication of vascular surgery. Optimal management of Actinomyces spp. prosthetic vascular graft infection (PVGI) is highly uncertain because of the paucity of reports on this disease. METHODS: We conducted a retrospective case-series of Actinomyces-PVGI that occurred in the last five years in two major university hospitals in northern Italy. We searched for previously published cases in the scientific literature. RESULTS: We report five original cases of Actinomyces spp. prosthetic vascular graft infection following aortic aneurysm repair. Our literature review retrieved eight similar cases. Most patients were immunocompetent males. Most infections were polymicrobial (11/13 cases), with a prevalence of A. odontolyticus involvement (3/13 cases were associated with. Salmonella spp. infection). All cases had a late presentation (≥4 months from graft placement), with 61% associated with an aorto-enteric fistula. All patients received antibiotic therapy, but the duration was highly heterogeneous (from two weeks to life-long antibiotics). The patients without surgical revision experienced septic recurrences (2/13), permanent dysfunction (1/13), or a fatal outcome (2/13), while of the remainder who underwent vascular graft explant, six recovered completely and one developed a periprosthetic abscess. In two cases follow-up was not available. CONCLUSIONS: This case-series aims to raise the diagnostic suspicion and to describe the current management of Actinomyces-PVGIs. We highlight a high heterogeneity in antibiotic duration, choice of the antibiotic regimen, and surgical management. Higher reporting rate is advisable to produce better evidence and optimize management of this rare complication of vascular surgery.

Trichosporon asahii Infective Endocarditis of Prosthetic Valve: A Case Report and Literature Review.

Trichosporon spp. endocarditis is a severe and hard-to-treat infection. Immunosuppressed subjects and carriers of prosthetic valves or intracardiac devices are at risk. This article presents the case of an immunocompetent 74-year-old man affected by endocarditis of the prosthetic aortic valve. After Bentall surgery, cultures of the removed valve demonstrated Trichosporon ashaii as the etiological agent. The patient was treated with amphotericin B at first and subsequently with fluconazole. Given the fragility of the patient and the aggressiveness of the pathogen, life-long prophylactic therapy with fluconazole was prescribed. After 5 years follow-up, no drug-related toxicities were reported and the patient never showed any signs of recurrence. The review of the literature illustrates that Trichosporon spp. endocarditis may present even many years after heart surgery, and it is often associated with massive valve vegetations, severe embolic complications, and unfavorable outcome. Due to the absence of international guidelines, there is no unanimous therapeutic approach, but amphotericin B and azoles are usually prescribed. Additionally, a prompt surgical intervention seems to be of paramount importance. When dealing with a life-threatening disease, such as mycotic endocarditis of prosthetic valves, it is essential to consider and treat even rare etiological agents such as Trichosporon spp.

Strongyloides stercoralis infection: an underlying cause of invasive bacterial infections of enteric origin. Results from a prospective cross-sectional study of a northern Italian tertiary hospital.

PURPOSE OF THE STUDY: We assessed the prevalence of S. stercoralis in a cohort of inpatients with invasive bacterial infections of enteric origin to investigate whether the parasite may facilitate these bacterial infections even in the absence of larval hyperproliferation. METHODS: We performed a prospective cross-sectional study in a hospital in northern Italy. Subjects admitted due to invasive bacterial infection of enteric origin and potential previous exposure to S. stercoralis were systematically enrolled over a period of 10 months. S. stercoralis infection was investigated with an in-house PCR on a single stool sample and with at least one serological method (in-house IFAT and/or ELISA Bordier). Univariate, bi-variate and logistic regression analyses were performed. RESULTS: Strongyloidiasis was diagnosed in 14/57 patients (24.6%; 95% confidence interval 14.1-37.8%) of which 10 were Italians (10/49, 20.4%) and 4 were migrants (4/8, 50.0%). Stool PCR was performed in 43/57 patients (75.4%) and no positive results were obtained. Strongyloidiasis was found to be significantly associated (p ≤ 0.05) with male gender, long international travels to areas at higher endemicity, deep extra-intestinal infectious localization and solid tumors. In the logistic regression model, increased risk remained for the variables deep extra-intestinal infectious localization and oncologic malignancy. CONCLUSIONS: Our findings suggest a new role of chronic strongyloidiasis in favoring invasive bacterial infections of enteric origin even in the absence of evident larval dissemination outside the intestinal lumen. Further well-designed studies should be conducted to confirm our results, and possibly establish the underlying mechanisms.

Drivers determining tuberculosis disease screening yield in four European screening programmes: a comparative analysis.

BACKGROUND: The World Health Organization End TB Strategy emphasises screening for early diagnosis of tuberculosis (TB) in high-risk groups, including migrants. We analysed key drivers of TB yield differences in four large migrant TB screening programmes to inform TB control planning and feasibility of a European approach. METHODS: We pooled individual TB screening episode data from Italy, the Netherlands, Sweden and the UK, and analysed predictors and interactions for TB case yield using multivariable logistic regression models. RESULTS: Between 2005 and 2018 in 2 302 260 screening episodes among 2 107 016 migrants to four countries, the programmes identified 1658 TB cases (yield 72.0 (95% CI 68.6-75.6) per 100 000). In logistic regression analysis, we found associations between TB screening yield and age (≥55 years: OR 2.91 (95% CI 2.24-3.78)), being an asylum seeker (OR 3.19 (95% CI 1.03-9.83)) or on a settlement visa (OR 1.78 (95% CI 1.57-2.01)), close TB contact (OR 12.25 (95% CI 11.73-12.79)) and higher TB incidence in the country of origin. We demonstrated interactions between migrant typology and age, as well as country of origin. For asylum seekers, the elevated TB risk remained similar above country of origin incidence thresholds of 100 per 100 000. CONCLUSIONS: Key determinants of TB yield included close contact, increasing age, incidence in country of origin and specific migrant groups, including asylum seekers and refugees. For most migrants such as UK students and workers, TB yield significantly increased with levels of incidence in the country of origin. The high, country of origin-independent TB risk in asylum seekers above a 100 per 100 000 threshold could reflect higher transmission and re-activation risk of migration routes, with implications for selecting populations for TB screening.

A scoping review on the risk of tuberculosis in specific population groups: can we expand the World Health Organization recommendations?

Since 2015, the World Health Organization (WHO) has recommended prioritising testing and treatment of tuberculosis (TB) infection (TBI) in 11 high-risk groups. With new options emerging for TB preventive treatment, we conducted a scoping review, in consultation with the WHO's Global Tuberculosis Programme, to explore the evidence for other population groups at potentially high risk of progression to active TB. We searched six databases for preprints and articles published between 2000 and August 2022. 18 out of 33 668 screened records were included (six meta-analyses and 12 original research studies). Most were observational studies reporting the incidence of active TB in a risk group versus control. Glomerular diseases had the strongest association with active TB (standardised incidence ratio 23.36, 95% CI 16.76-31.68) based on an unpublished study. Other conditions associated with increased risk of active TB included hepatitis C, malignancies, diabetes mellitus, rheumatoid arthritis and vitamin D deficiency. Corticosteroid use was also associated with increased risk in several studies, although heterogeneous definitions of exposure and indications for use challenge interpretation. Despite methodological limitations of the identified studies, expanding the recommendations for TBI screening and treatment to new risk groups such as those reported here should be considered. Further group-specific systematic reviews may provide additional data for decision-making.

Atypical monkeypox presentation in a previously vaccinated MSM HIV-positive adult.

The outbreak of monkeypox virus (MPXV) in non-endemic countries is an international public health emergency, and the diversity in manifestations poses challenges for early diagnosis and isolation. We describe an atypical case of monkeypox (MPX) in a 46-year-old homosexual male living with HIV. He reported 1-day duration fever, a lesion on his chin that, over a period of 18 days, had gradually enlarged and ulcerated. Biopsy examination performed at an external centre revealed pyoderma gangrenosum, unconfirmed at a subsequent biopsy. When he reported to our hospital outpatients' clinic the chin lesion had a diameter of 5 × 5 cm, necrotic margins and ulcerated base and signs of superinfection. He was admitted for further investigations. Three swabs collected from pharynx, skin and chin lesion resulted positive for MPXV. He had a favourable clinical course and was discharged soon after. Pending the achievement of optimal vaccination coverage in at-risk groups, early identification and isolation of infectious patients represent the cornerstones of the containment strategy. Atypical cases of MPX manifestations are not uncommon, particularly in patients with HIV infection. A high level of suspicion should be maintained to identify infectious cases at an early stage and avoid further spread of the infection.

Disseminated Kaposi sarcoma following COVID-19 in a 61-year-old Albanian immunocompetent man: a case report and review of the literature.

BACKGROUND: COVID-19 and its related anti-inflammatory treatment (steroids, immunomodulators) may induce the reactivation of latent bacterial, parasitic, and viral infections. According to our knowledge, no case of disseminated HHV-8-related Kaposi sarcoma (KS) after COVID-19 and its treatment has been described so far. Only one case of cutaneous KS concurrently with COVID-19 has been previously reported. CASE PRESENTATION: We describe a case of disseminated KS in a 61-year-old immunocompetent Albanian man after hospitalization for COVID-19. METHODS FOR LITERATURE RESEARCH: We used PubMed as biomedical database for the literature research. We selected keyword combinations including "Kaposi sarcoma," "HHV-8," "immunocompetent," "COVID-19," "SARS-CoV-2," and "steroids." No time or language limitation was set. Titles and abstracts of selected articles were systematically screened. Articles were included in the examination if they were published under free access through the digital library of the University of Brescia (Italy), and provided full text. Articles were excluded if the topic was beyond the aim of our study. Finally, we selected 15 articles. RESULTS: We describe a case of KS in COVID-19 patient and postulate that Interleukin-6 (IL-6) activity and steroid-induced immunodeficiency may play a major role in KS emergence. No published case of disseminated KS following COVID-19 in otherwise healthy individuals was found through the systematic literature review, despite the high incidence of COVID-19 in areas with medium-high prevalence of HHV-8 infection. This observation might be explained by the role of individual genetic susceptibility factors. CONCLUSIONS: SARS-CoV-2 infection and its treatment may lead to reactivation of several latent infections, including HHV-8 and its related clinical syndrome, Kaposi sarcoma.

Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia, Italy.

A hyperinflammatory syndrome (HIS) may cause a life-threatening acute respiratory distress syndrome (ARDS) in patients with COVID-19 pneumonia. A prospective series of 100 consecutive patients admitted to the Spedali Civili University Hospital in Brescia (Italy) between March 9th and March 20th with confirmed COVID-19 pneumonia and ARDS requiring ventilatory support was analyzed to determine whether intravenous administration of tocilizumab (TCZ), a monoclonal antibody that targets the interleukin 6 (IL-6) receptor, was associated with improved outcome. Tocilizumab was administered at a dosage of 8 mg/kg by two consecutive intravenous infusions 12 h apart. A third infusion was optional based on clinical response. The outcome measure was an improvement in acute respiratory failure assessed by means of the Brescia COVID Respiratory Severity Score (BCRSS 0 to 8, with higher scores indicating higher severity) at 24-72 h and 10 days after tocilizumab administration. Out of 100 treated patients (88 M, 12 F; median age: 62 years), 43 received TCZ in the intensive care unit (ICU), while 57 in the general ward as no ICU beds were available. Of these 57 patients, 37 (65%) improved and suspended noninvasive ventilation (NIV) (median BCRSS: 1 [IQR 0-2]), 7 (12%) patients remained stable in NIV, and 13 (23%) patients worsened (10 died, 3 were admitted to ICU). Of the 43 patients treated in the ICU, 32 (74%) improved (17 of them were taken off the ventilator and were discharged to the ward), 1 (2%) remained stable (BCRSS: 5) and 10 (24%) died (all of them had BCRSS≥7 before TCZ). Overall at 10 days, the respiratory condition was improved or stabilized in 77 (77%) patients, of whom 61 showed a significant clearing of diffuse bilateral opacities on chest x-ray and 15 were discharged from the hospital. Respiratory condition worsened in 23 (23%) patients, of whom 20 (20%) died. All the patients presented with lymphopenia and high levels of C-reactive protein (CRP), fibrinogen, ferritin and IL-6 indicating a HIS. During the 10-day follow-up, three cases of severe adverse events were recorded: two patients developed septic shock and died, one had gastrointestinal perforation requiring urgent surgery and was alive at day 10. In conclusion, our series showed that COVID-19 pneumonia with ARDS was characterized by HIS. The response to TCZ was rapid, sustained, and associated with significant clinical improvement.

App-based symptoms screening with Xpert MTB/RIF Ultra assay used for active tuberculosis detection in migrants at point of arrivals in Italy: The E-DETECT TB intervention analysis.

BACKGROUND: From 2014 to 2017, the number of migrants who came to Italy via the Mediterranean route has reached an unprecedented level. The majority of refugees and migrants were rescued in the Central Mediterranean and disembarked at ports in the Sicily region. Rapid on-spot active TB screening intervention at the point of arrival will cover most migrants arriving in EU and by detecting TB prevalent cases will limit further transmission of the disease. MATERIAL AND METHODS: Between November 2016 and December 2017 newly arrived migrants at point of arrivals in Sicily, were screened for active Tuberculosis using a smartphone application, followed in symptomatic individuals by fast molecular test, Xpert MTB/RIF Ultra, on collected sputum samples. RESULTS: In the study period 3787 migrants received a medical evaluation. Eight hundred and ninety-one (23.5%) reported at least one protocol-defined Tuberculosis symptom. Fifteen (2.7%) were positive to at least one microbiological test revealing a post-entry screening prevalence rate of 396 per 100.000 individuals screened (95% CI: 2.22-6.53). In logistic regression analysis, those with cough and at least one other symptom had an increased probability of testing positive compared to persons with symptoms other than cough. Whole-genome-sequencing demonstrate two separate cases of transmission. DISCUSSION: To our knowledge this study reports first-time results of an active TB case finding strategy based on on-spot symptom screening using a smartphone application, followed by fast molecular test on collected sputum samples. Our preliminary findings reveal a post-entry screening prevalence rate of 396 per 100.000 individuals screened (95% CI: 2.22-6.53).

Building a European database to gather multi-country evidence on active and latent TB screening for migrants.

BACKGROUND AND AIM: Screening for active and latent TB among migrants in low TB incidence countries may constitute an important contribution to TB elimination. E-DETECT TB, a European multi-county collaboration, aims to address the present lack of evidence on effectiveness of migrant TB screening by collating data in an international database and perform cross-country pooled and comparative analyses of screening coverage, results and linkage to care. METHOD: A database was established using migrant TB screening data from participating countries' national screening programs, national screening pilots and local research projects. All partner countries contributed to a common agreed protocol with standardized variables, pooling available numerator and denominator screening data from participating countries and sites. RESULTS: All collaborating members drafted and agreed upon a data sharing accord as well as a protocol that clearly defined responsibilities and data governance principles. The database has been created and data transfer is ongoing. CONCLUSION: By persistence and focus the project has overcome considerable administrative, practical and legal challenges. This international collaboration provides greater power of analysis of harmonized data and thereby a unique opportunity to contribute migrant TB screening evidence. E-DETECT TB has started to invite other countries to contribute data to the database.

Multidisciplinary approach to prostatitis.

The modern clinical research on prostatitis started with the work of Stamey and coworkers who developed the basic principles we are still using. They established the segmented culture technique for localizing the infections in the males to the urethra, the bladder, or the prostate and to differentiate the main categories of prostatitis. Such categories with slight modifications are still used according to the NIH classification: acute bacterial prostatitis, chronic bacterial prostatitis, Chronic Pelvic Pain Syndrome (CPPS) and asymptomatic prostatitis. Prostatic inflammation is considered an important factor in influencing both prostatic growth and progression of symptoms of benign prostatic hyperplasia and prostatitis. Chronic inflammation/neuroinflammation is a result of a deregulated acute phase response of the innate immune system affecting surrounding neural tissue at molecular, structural and functional levels. Clinical observations suggest that chronic inflammation correlates with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and benign prostatic hyperplasia (BPH) and an history of clinical chronic prostatitis significantly increases the odds for prostate cancer. The NIHNIDDK classification based on the use of the microbiological 4- glasses localization test or simplified 2-glasses test, is currently accepted worldwide. The UPOINT system identifies groups of clinicians with homogeneous clinical presentation and is used to recognize phenotypes to be submitted to specific treatments. The UPOINTS algorithm implemented the original UPOINT adding to the urinary domains (U), psycho-social (P), organspecific (O), infection (I), neurological (N), muscle tension and tenderness (T) a further domain related to sexuality (S). In fact sexual dysfunction (erectile, ejaculatory, libido loss) has been described in 46-92% of cases with a high impact on the quality of life of patients with CP/CPPS. Prostatic ultrasound represents the most popular imaging test in the work-up of either acute and chronic prostatitis although no specific hypo-hyperechoic pattern has been clearly associated with chronic bacterial prostatitis and CPPS. Use of a digital-processing software to calculate the extension of prostatic calcification area at ultrasound demonstrated a higher percentage of prostatic calcification in patients with chronic bacterial prostatitis. Multiparametric Magnetic Resonance Imaging (mpMRI) is the current state-of-the art imaging modality in the assessment of patients with prostate cancer although a variety of benign conditions, including inflammation, may mimic prostate cancer and act as confounding factors in the discrimination between neoplastic and non-neoplastic lesions. Bacteria can infect prostate gland by: ascending the urethra, reflux of urine into the prostatic ducts, direct inoculation of bacteria through inserted biopsy needles or hematogenous seeding. Enterobacteriaceae are the predominant pathogens in acute and chronic bacterial prostatitis, but an increasing role of Enterococci has been reported. Many strains of these uropathogens exhibit the ability to form biofilm and multidrug- resistance. Sexually Transmitted Infections (STI) agents, in particular Chlamydia trachomatis and Mycoplasma genitalium, have been also considered as causative pathogens of chronic bacterial prostatitis. On the contrary the effective role in genital diseases of other "genital mycoplasmas" is still a much debated issue. Sexually Transmitted Infections agents should be investigated by molecular methods in both patient and sexual partner. "Next generation" investigations, such as cytokine analysis, cytological typing of immune cells could help stratifying the immune response. Epigenetic dysregulation of inflammatory factors should be investigated according to systemic and compartment-specific signals. The search for biomarkers should also include evaluation of hormonal pathways, as measurement of estrogen levels in semen. Antimicrobials are the first line agents for the treatment of bacterial prostatitis. The success of antimicrobial treatment depends on the antibacterial activity and the pharmacokinetic characteristics of the drug which must reach high concentrations in prostate secretion and prostate tissue. Acute bacterial prostatitis can be a serious infection with a potential risk for urosepsis For iInitial treatment of severely ill patients, intravenous administration of high doses of bactericidal antimicrobials, such as broad-spectrum penicillins, third-generation cephalosporins or fluoroquinolones, is recommended in combination with an aminoglycoside. Use of piperacillin-tazobactam and meropenem is justified in presence of multiresistant gramnegative pathogens. The antibiotic treatment of chronic prostatitis is currently based on the use of fluoroquinolones that, given for 2 to 4 weeks, cured about 70% of men with chronic bacterial prostatitis. For the treatment of Chlamydial prostatitis macrolides were shown to be more effective than fluoroquinolones, whereas no differences were observed in microbiological and clinical efficacy between macrolides and tetracyclines for the treatment of infections caused by intracellular pathogens. Aminoglycosides and fosfomycin could be considered as a therapeutic alternative for the treatment of quinolone resistant prostatitis. Use of alpha-blockers in CP/CPPS patients with urinary symptoms and analgesics +/- non steroidal anti-inflammatory drugs (NSAID), in presence of pain demonstrated a reduction of symptoms reduction and an improvement of quality of life, although long term use of NSAID is limited by side effect profile. However, the multimodal therapeutic regimen by contemporary use of alphablockers, antibiotics and anti-inflammatory showed a better control of prostatitis symptoms than single drug treatment. Novel therapeutic substances for the treatment of pain, such as the cannabinoid anandamide would be highly interesting to test. An alternative for the treatment of chronic prostatitis/chronic pelvic pain syndrome is phytotherapy, as primary therapy or in association with other drugs. Quercetin, pollen extract, extract of Serenoa repens and other mixtures of herbal extracts showed a positive effect on symptoms and quality of life without side effects. The association of CP/CPPS with alterations of intestinal function has been described. Diet has its effects on inflammation by regulation of the composition of intestinal flora and direct action on the intestinal cells (sterile inflammation). Intestinal bacteria (microbiota) interacts with food influencing the metabolic, immune and inflammatory response of the organism. The intestinal microbiota has protective function against pathogenic bacteria, metabolic function by synthesis of vitamins, decomposition of bile acids and production of trophic factors (butyrate), and modulation of the intestinal immune system. The alteration of the microbiota is called "dysbiosis" causing invasive intestinal diseases pathologies (leaky gut syndrome and food intolerances, irritable bowel syndrome or chronic inflammatory bowel diseases) and correlating with numerous systemic diseases including acute and chronic prostatitis. Administration of live probiotics bacteria can be used to regulate the balance if intestinal flora. Sessions of hydrocolontherapy can represent an integration to this therapeutic approach. Finally, microbiological examination of sexual partners can offer supplementary information for treatment.

Incident genital HPV infections and potential impact of HPV vaccines in adult women living with HIV/AIDS.

This study aims to describe and characterize incident HR-HPV infections and associated diseases in HIV-infected women. 805 HIV-infected women enrolled in the VALHIDATE Study were screened and followed-up for HPV by co-testing. Social, behavioral and health data were collected. HPV-DNA positive samples were typed using a commercial kit or RFLP analysis. Conventional Pap-smears were evaluated using the 2001 Bethesda System. The participants with abnormal cytological results were referred for colposcopy. 565 HIV-infected women (median age: 43 years) were analysed, 40.9% had >5 lifetime sexual partners, 77.2% contracted HIV through sexual intercourse, 93% were receiving antiretroviral treatment and 77.3% had undetectable HIV-RNA. The women underwent 1254 follow-ups (median follow-up: 33 months) for 1430.6 PersonYear-Follow-Up. 37.4% of baseline HPV-negative women acquired incident HPV-infections, 69.6% of which were HR-HPVs. HPV-53 was the most common HPV type detected (9.3%). 18.2% of women showed incident or progressive cytological abnormalities (7.8% ASC-US, 9.7% LSIL and 0.6% HSIL) and colposcopy revealed CIN2 (N = 2), CIN1 (N = 2) and VIN3 (N = 1). The preventable fraction of incident infections was 11.3%, 16.7%, and 35.2% for the 2v-4v-9v-HPV vaccines respectively (χ2 p < 0.0001). The overall burden of incident lesions attributable to the vaccine types were 9.1% for 2v-, 14.5% for 4v- and 30.9% for 9v-vaccine. High HPV incidence rates and high percentages of multiple HR-HPV infections were observed in a cohort of HIV-infected women receiving effective antiretroviral treatment. Primary prevention strategies based on the new 9v-HPV vaccine may help to prevent incident infections and disease progression in this cohort of women.

Screening for active and latent tuberculosis among asylum seekers in Italy: A retrospective cohort analysis.

BACKGROUND: The World Health Organization conditionally recommends systematic screening of tuberculosis (TB) and Latent Tuberculosis Infection (LTBI) among asylum seekers (AS) from high-burden countries, but the effectiveness of different screening approaches is controversial. METHODS: We report the results of a retrospective cohort analysis of TB and LTBI screening among consecutive AS in Brescia, Italy during 2015-2016. TB screening was based on symptoms, LTBI screening on the tuberculin skin test (TST). Logistic regression analysis was performed to identify factors associated with screening uptake. RESULTS: Of 2904 registered AS 2567 (88.4%) were evaluated for TB, 62 (2.4%) had symptoms and active TB yield was 155/100,000. Prevalence and incidence TB rates were 545/100,000 persons and 220/100,000 person-years. Questionnaire screening identified 28.6% (4/14) prevalent cases. Of 2303 (89.7%) AS with TST result, the positivity rate was 36.6% (843/2303). Of the 843 candidates for LTBI treatment 413 (49.0%) completed the screening. LTBI treatment was prescribed to 190 (47.9%) of 397 eligible individuals, 10.8% (91) completed treatment. CONCLUSIONS: TB prevalence and incidence rates were high in this AS population, but symptom-based screening performed poorly. LTBI cascade losses were significant and mainly attributable to the defragmentation of the health care system.

The Italian registry of pulmonary non-tuberculous mycobacteria - IRENE: the study protocol.

BACKGROUND: A substantial increase in pulmonary and extra-pulmonary diseases due to non-tuberculous mycobacteria (NTM) has been documented worldwide, especially among subjects suffering from chronic respiratory diseases and immunocompromised patients. Many questions remain regarding the epidemiology of pulmonary disease due to NTM (NTM-PD) mainly because reporting of NTM-PD to health authorities is not mandated in several countries, including Italy. This manuscript describes the protocol of the first Italian registry of adult patients with respiratory infections caused by NTM (IRENE). METHODS: IRENE is an observational, multicenter, prospective, cohort study enrolling consecutive adult patients with either a NTM respiratory isolate or those with NTM-PD. A total of 41 centers, including mainly pulmonary and infectious disease departments, joined the registry so far. Adult patients with all of the following are included in the registry: 1) at least one positive culture for any NTM species from any respiratory sample; 2) at least one positive culture for NTM isolated in the year prior the enrolment and/or prescribed NTM treatment in the year prior the enrolment; 3) given consent to inclusion in the study. No exclusion criteria are applied to the study. Patients are managed according to standard operating procedures implemented in each IRENE clinical center. An online case report form has been developed to collect patients' demographics, comorbidities, microbiological, laboratory, functional, radiological, clinical, treatment and outcome data at baseline and on an annual basis. An IRENE biobank has also been developed within the network and linked to the clinical data of the registry. CONCLUSIONS: IRENE has been developed to inform the clinical and scientific community on the current management of adult patients with NTM respiratory infections in Italy and acts as a national network to increase the disease's awareness. TRIAL REGISTRATION: Clinicaltrial.gov: NCT03339063.

The effectiveness and cost-effectiveness of screening for latent tuberculosis among migrants in the EU/EEA: a systematic review.

BackgroundMigrants account for a large and growing proportion of tuberculosis (TB) cases in low-incidence countries in the European Union/European Economic Area (EU/EEA) which are primarily due to reactivation of latent TB infection (LTBI). Addressing LTBI among migrants will be critical to achieve TB elimination. Methods: We conducted a systematic review to determine effectiveness (performance of diagnostic tests, efficacy of treatment, uptake and completion of screening and treatment) and a second systematic review on cost-effectiveness of LTBI screening programmes for migrants living in the EU/EEA. Results: We identified seven systematic reviews and 16 individual studies that addressed our aims. Tuberculin skin tests and interferon gamma release assays had high sensitivity (79%) but when positive, both tests poorly predicted the development of active TB (incidence rate ratio: 2.07 and 2.40, respectively). Different LTBI treatment regimens had low to moderate efficacy but were equivalent in preventing active TB. Rifampicin-based regimens may be preferred because of lower hepatotoxicity (risk ratio = 0.15) and higher completion rates (82% vs 69%) compared with isoniazid. Only 14.3% of migrants eligible for screening completed treatment because of losses along all steps of the LTBI care cascade. Limited economic analyses suggest that the most cost-effective approach may be targeting young migrants from high TB incidence countries. Discussion: The effectiveness of LTBI programmes is limited by the large pool of migrants with LTBI, poorly predictive tests, long treatments and a weak care cascade. Targeted LTBI programmes that ensure high screening uptake and treatment completion will have greatest individual and public health benefit.

The effectiveness and cost-effectiveness of screening for active tuberculosis among migrants in the EU/EEA: a systematic review.

BACKGROUND: The foreign-born population make up an increasing and large proportion of tuberculosis (TB) cases in European Union/European Economic Area (EU/EEA) low-incidence countries and challenge TB elimination efforts. Methods: We conducted a systematic review to determine effectiveness (yield and performance of chest radiography (CXR) to detect active TB, treatment outcomes and acceptance of screening) and a second systematic review on cost-effectiveness of screening for active TB among migrants living in the EU/EEA. Results: We identified six systematic reviews, one report and three individual studies that addressed our aims. CXR was highly sensitive (98%) but only moderately specific (75%). The yield of detecting active TB with CXR screening among migrants was 350 per 100,000 population overall but ranged widely by host country (110-2,340), migrant type (170-1,192), TB incidence in source country (19-336) and screening setting (220-1,720). The CXR yield was lower (19.6 vs 336/100,000) and the numbers needed to screen were higher (5,076 vs 298) among migrants from source countries with lower TB incidence (≤ 50 compared with ≥ 350/100,000). Cost-effectiveness was highest among migrants originating from high (> 120/100,000) TB incidence countries. The foreign-born had similar or better TB treatment outcomes than those born in the EU/EEA. Acceptance of CXR screening was high (85%) among migrants. Discussion: Screening programmes for active TB are most efficient when targeting migrants from higher TB incidence countries. The limited number of studies identified and the heterogeneous evidence highlight the need for further data to inform screening programmes for migrants in the EU/EEA.

Antiretroviral Therapy in HIV-Infected Children With Tuberculosis: A Systematic Review.

BACKGROUND: Tuberculosis (TB) is the major cause of mortality in HIV-infected children globally. Current guidelines about the management of antiretroviral therapy in children with TB are based on a limited number of nonrandomized studies involving small numbers of participants. The aim of the study was to systematically retrieve and critically appraise available evidence on the efficacy and safety of different antiretroviral regimens in children with HIV infection who are receiving treatment for active TB. METHODS: We conducted a systematic review of the literature according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Records were retrieved through March 2016 from Medline, Embase and manual screening of key conference proceedings. Four specific research questions assessing available treatment options were defined. RESULTS: Although 4 independent searches were conducted (1 for each Population, Intervention, Comparator, Outcomes question), results were elaborated and interpreted together because of significant overlap among the retrieved records. Six observational studies were selected for qualitative synthesis while meta-analysis could not be performed. CONCLUSION: Evidence for optimal treatment options for HIV/TB coinfected children is limited. As the global community strives to reach the fast-track HIV treatment targets and eliminate childhood TB deaths, it must ensure that coinfected children are included in key treatment studies and expand this neglected but crucial area of research.

Socioeconomic status and biomedical risk factors in migrants and native tuberculosis patients in Italy.

Action on social determinants is a main component of the World Health Organization End Tuberculosis (TB) Strategy. The aim of the study was to collect information on socioeconomic characteristics and biomedical risk factors in migrant TB patients in Italy and compare it with data collected among Italian TB patients. A cross-sectional study was conducted among TB patients aged ≥18 years over a 12-months enrolment period in 12 major Italian hospitals. Information on education, employment, housing and income was collected, and European Union Statistics on Income and Living Conditions index was used to assess material deprivation. Among migrants, we also analyzed factors associated with severe material deprivation. Migrants were compared with younger (18-64 years) and older (65+ years) Italians patients. Out of 755 patients enrolled (with a median age of 42 years, interquartile range: 31-53), 65% were migrants. Pulmonary, microbiologically confirmed, and new cases were 80%, 73%, and 87% respectively. Prevalence of co-morbidities (i.e. diabetes, chronic kidney disease, neoplastic diseases and use of immunosuppressive drugs) was lower among migrants compared to Italian TB patients, while indicators of socioeconomic status, income and housing conditions were worst in migrants. Forty-six percent of migrants were severely deprived vs. 9% of Italians (p<0.0001, 11.3% and 5.5% among younger and older Italians, respectively). Among migrants, being male, older, irregular, unemployed, with a shorter time spent in Italy, a lower education level, and without a co-morbidity diagnosis were factors associated with severe material deprivation at multi-variable logistic regression. Moreover, socioeconomic indicators for Italian patients did not differ from those reported for the general Italian population, while migrant TB patients seem to have a higher prevalence of severe material deprivation than other migrants residing in Italy. Intervention to address the needs of this population are urgent.

Breaking the barriers: Migrants and tuberculosis.

Tuberculosis (TB) can represent an important clinical and public health in developing and developed countries. Low- and middle-income countries are facing an epidemic which is difficult to address because of the drug-resistance spread and the association of TB with HIV/AIDS. High-income countries, whose TB incidence has decreased in the last decades, can be involved in new TB epidemic waves owing to social, healthcare, and economic hurdles and challenges. In particular, migrants coming from high TB incidence countries can represent a new epidemiological issue in the TB care and control in geographical areas where primary care and specialized centres are not equipped to face the clinical and public health issues associated with the TB disease. The healthcare management of individuals with a latent TB infection or the TB disease is heterogeneous and different policies are in place in Europe, and, specifically, in EU countries. Scientific evidence on how to early and efficiently detect TB cases is missing, as well as diagnostic tools to diagnose those who have latent TB infection do not show adequate accuracy. Countries like Greece and Italy have political difficulties in the management of migrants and the poor living conditions in the migration centres can increase the probability of Mycobacterium tuberculosis transmission. A clear advocacy and political commitment are urgently required. The current migration trends represent a threat from a human and a healthcare perspective. New homogeneous and target-oriented policies and strategies are needed to improve the health of the migrant and of the autochthonous populations.