Drugs for treating infections caused by non-tubercular mycobacteria: a narrative review from the study group on mycobacteria of the Italian Society of Infectious Diseases and Tropical Medicine.

BACKGROUND: Non-tuberculous mycobacteria (NTM) are generally free-living organism, widely distributed in the environment, with sporadic potential to infect. In recent years, there has been a significant increase in the global incidence of NTM-related disease, spanning across all continents and an increased mortality after the diagnosis has been reported. The decisions on whether to treat or not and which drugs to use are complex and require a multidisciplinary approach as well as patients' involvement in the decision process. METHODS AND RESULTS: This review aims at describing the drugs used for treating NTM-associated diseases emphasizing the efficacy, tolerability, optimization strategies as well as possible drugs that might be used in case of intolerance or resistance. We also reviewed data on newer compounds highlighting the lack of randomised clinical trials for many drugs but also encouraging preliminary data for others. We also focused on non-pharmacological interventions that need to be adopted during care of individuals with NTM-associated diseases CONCLUSIONS: Despite insufficient efficacy and poor tolerability this review emphasizes the improvement in patients' care and the needs for future studies in the field of anti-NTM treatments.

Could anti-HCV treatment prevent recurrence of hepatocellular carcinoma in HIV-infected patients? Two case reports.

Highly active antiretroviral therapy (HAART) has proven long-term efficacy in human immunodeficiency virus (HIV) infection. Combination therapy with pegylated interferon and ribavirin has become the standard of care in patients with both hepatitis C virus (HCV) chronic hepatitis and HIV/HCV co-infection. Data on the safety and efficacy of combination therapy in chronic hepatitis C patients with hepatocellular carcinoma (HCC) is scarce and even more so in HIV/HCV co-infected subjects. We report the successful administration of both HAART and anti-HCV therapies in two HIV/HCV co-infected patients after HCC eradication. These encouraging results might argue for the feasibility of an aggressive approach in the management of co-infected patients with HCC.

A systematic review of the costs of diagnosis for multidrug-resistant/extensively drug-resistant TB in different settings.

BACKGROUND: We performed an analysis of the cost and relative merits of different strategies for the diagnosis of multidrug-resistant/extensively drug-resistant TB (MDR/XDR-TB) in different settings.METHODS: We systematically reviewed the published evidence on cost/cost-effectiveness of rapid MDR/pre-XDR-TB and other methods for XDR-TB testing up to September 2022. PRISMA guidelines were followed. Collected data were analysed using Stata v17 software. Cost data were reported in USD ($) and summarised by mean, standard deviation, and range. Country income level was defined according to the World Bank country classification. Three simplified scenarios were also used to explore testing implications, based on low, intermediate and high TB incidence.RESULTS: Of 157 records, 25 studies were included with 24 reporting the cost of Xpert/RIF and two that evaluated the implementation of the MTBDRplus test. The total rapid test cost ranged from $12.41-$218, including $1.13-$74.60 for reagents/consumables and $0.40-$14.34 for equipment.CONCLUSION: The cost of MDR/XDR-TB diagnostics is lower in low resource settings. However, the cost-effective implementation of MDR/XDR-TB diagnostic algorithms requires careful consideration of local resources to avoid missed identification and the use of inappropriate regimen.

Vaccination in post-tuberculosis lung disease management: A review of the evidence.

INTRODUCTION AND OBJECTIVES: Post-tuberculosis lung disease (PTLD), as other chronic respiratory disorders, may have infectious complications; some of them can be prevented with vaccinations. So far, no document has discussed the potential role of vaccination in PTLD. Therefore, the objective of this review was to describe vaccination recommendations to prevent infections potentially capable of complicating PTLD. MATERIALS AND METHODS: A non-systematic review of the literature was conducted. The following keywords were used: tuberculosis, vaccination, vaccines and PTLD. PubMed/MEDLINE and Embase were used as the search engine, focusing on English-language literature only. RESULTS: We identified 9 vaccines potentially useful in PTLD. Influenza, pneumococcal and anti-COVID-19 vaccinations should be recommended. Patients with PTLD can also benefit from vaccination against shingles. Vaccination against pertussis is mainly relevant during childhood. Diphtheria, tetanus and measles vaccination are recommended for general population and should be considered in patients with PTLD not previously vaccinated. Tdap (Tetanus, diphtheria, and pertussis) booster should be repeated in every adult every ten years. Vaccination against BCG retains its importance during early childhood in countries where TB is endemic. CONCLUSIONS: Vaccination deserves to be considered among the strategies to prevent and/or mitigate PTLD complications. Further evidence is necessary to better understand which vaccines have the greatest impact and cost-benefit.

Clinical standards for diagnosis, treatment and prevention of post-COVID-19 lung disease.

BACKGROUND: The aim of these clinical standards is to provide guidance on 'best practice' care for the diagnosis, treatment and prevention of post-COVID-19 lung disease.METHODS: A panel of international experts representing scientific societies, associations and groups active in post-COVID-19 lung disease was identified; 45 completed a Delphi process. A 5-point Likert scale indicated level of agreement with the draft standards. The final version was approved by consensus (with 100% agreement).RESULTS: Four clinical standards were agreed for patients with a previous history of COVID-19: Standard 1, Patients with sequelae not explained by an alternative diagnosis should be evaluated for possible post-COVID-19 lung disease; Standard 2, Patients with lung function impairment, reduced exercise tolerance, reduced quality of life (QoL) or other relevant signs or ongoing symptoms ≥4 weeks after the onset of first symptoms should be evaluated for treatment and pulmonary rehabilitation (PR); Standard 3, The PR programme should be based on feasibility, effectiveness and cost-effectiveness criteria, organised according to local health services and tailored to an individual patient's needs; and Standard 4, Each patient undergoing and completing PR should be evaluated to determine its effectiveness and have access to a counselling/health education session.CONCLUSION: This is the first consensus-based set of clinical standards for the diagnosis, treatment and prevention of post-COVID-19 lung disease. Our aim is to improve patient care and QoL by guiding clinicians, programme managers and public health officers in planning and implementing a PR programme to manage post-COVID-19 lung disease.

Blood born viral infections, sexually transmitted diseases and latent tuberculosis in italian prisons: a preliminary report of a large multicenter study.

BACKGROUND: Recent screenings of inmates for Hepatitis C virus (HCV), Hepatitis B virus (HBV), human immunodeficiency virus (HIV), Syphilis and Latent Tuberculosis (LTB) did not provide sufficient information to improve healthcare strategies. AIM: To obtain valuable information on the endemicity of the above mentioned Infections in prisons of Italy. MATERIALS AND METHODS: A screening based on a peer-to-peer communication, followed by a month of blood sampling on a voluntary basis was performed to detect antibody to 4 of the 5 above mentioned infections and detect LTB by PPD (purified protein derivative) Skin Test. The present analysis regards data obtained in 9 of the 20 prisons. RESULTS: The percentage of patients who accepted the screening varied between jails (37.3-95.2%, median 62.2), but it was higher than 10.0-20.5% obtained in the same 9 prisons using traditional methods before our intervention. The participation to the screening reached 65.3% for HBV, 64.6% for HCV, 67.4%for HIV, 55.7% for TPHA (Treponema Pallidum Hemagglutination Assay) and 42.8% for LTB. HBsAg was detected in 4.4% of 2265 subjects, anti-HCV in 22.8% of 2241, anti-HIV in 3.8% of 2339 and TPHA in 2.1% of 1932; PPD Skin Test was positive in 17.2% of 1486 subjects. The screening identified 183 subjects with an unknown infection, 56 italian and 127 foreigners to be evaluated for clinical decisions: 35 with HBV chronic infection, 34 with HCV chronic infection, 3 anti-HIV positive, 14 with syphilis and 97 with LTB. CONCLUSIONS: The new approach to the screening, based on a peer-to-peer communication followed by blood sampling on a voluntary basis provided valuable information to improve the healthcare system in each single prison.

Clinical standards for the assessment, management and rehabilitation of post-TB lung disease.

BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR).METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement).RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR.CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD.

Relevance of CD38 expression on CD8 T cells to evaluate antiretroviral therapy response in HIV-1-infected youths.

Surrogate markers for monitoring immuno-virological discordant responders, in addition to plasma viral load and CD4 cells, are still lacking. We assessed the diagnostic utility of CD38 expression on CD8 T cell assay, alone or in association with lymphocyte proliferation to mycotic antigens, in evaluating antiretroviral response. 28 vertically HIV-infected youths, 21 HAART- and seven 2 nucleotide reverse transcriptase inhibitors-treated, were enrolled in a retrospective study. Responders (57.1%) and non-responders (42.9%) to stable antiretroviral therapy for a minimum of 6 months, on the basis of viral load and CD4 T cells, comprehensively evaluated by CD38 expression on CD8 T lymphocytes [measured as CD38 antibody bound per CD8 T cell (CD38 ABC) and %CD38+ of total CD8 T cells (%CD38/CD8)] and lymphocyte proliferation to P. jiroveci, C. albicans, C. neoformans, A. fumigatus at a single time point after treatment, were selected. CD38 expression > or =2401 CD38 ABC and > or =85% CD38/CD8 cut-off points, accurately discriminates responders versus non-responders, both measures resulting in 75.0% (CI 42.8-94.5) sensitivity (identification of non-responder) and 93.8% (CI 69.8-99.8) specificity (identification of responder), when considered as single assays. The association '> or =2401 CD38 ABC or > or =85% CD38/CD8' improved sensitivity to 83.3% (CI 51.6-97.9), while the association '<2401 CD38ABC (or <85% CD38/CD8) and lymphoproliferative response positive to > or =2 tested organisms' improved specificity to 100% (CI 79.4-100). In conclusions, CD38 expression and mycotic antigen-specific T-cell proliferation may be used as additional parameters to existing criteria to evaluate antiretroviral response in immuno-virological discordant patients.

Tuberculosis, COVID-19 and migrants: Preliminary analysis of deaths occurring in 69 patients from two cohorts.

Little is known about the relationship between the COVID-19 and tuberculosis (TB). The aim of this study is to describe a group of patients who died with TB (active disease or sequelae) and COVID-19 in two cohorts. Data from 49 consecutive cases in 8 countries (cohort A) and 20 hospitalised patients with TB and COVID-19 (cohort B) were analysed and patients who died were described. Demographic and clinical variables were retrospectively collected, including co-morbidities and risk factors for TB and COVID-19 mortality. Overall, 8 out of 69 (11.6%) patients died, 7 from cohort A (14.3%) and one from cohort B (5%). Out of 69 patients 43 were migrants, 26/49 (53.1%) in cohort A and 17/20 (85.0%) in cohort B. Migrants: (1) were younger than natives; in cohort A the median (IQR) age was 40 (27-49) VS. 66 (46-70) years, whereas in cohort B 37 (27-46) VS. 48 (47-60) years; (2) had a lower mortality rate than natives (1/43, 2.3% versus 7/26, 26.9%; p-value: 0.002); (3) had fewer co-morbidities than natives (23/43, 53.5% versus 5/26-19.2%) natives; p-value: 0.005). The study findings show that: (1) mortality is likely to occur in elderly patients with co-morbidities; (2) TB might not be a major determinant of mortality and (3) migrants had lower mortality, probably because of their younger age and lower number of co-morbidities. However, in settings where advanced forms of TB frequently occur and are caused by drug-resistant strains of M. tuberculosis, higher mortality rates can be expected in young individuals.

Unexpected high rate of wild-type HIV-1 genotype among inmates failing antiretroviral therapy.

PURPOSE: Combination antiretroviral therapy (ART) has proven to be effective in treating human immunodeficiency virus (HIV) infection. Chronic administration of antiretrovirals presents significant challenges, including the risk of selecting treatment-resistant viral strains that can determine treatment failure and can be transmitted. In many countries, a large proportion of the HIV-infected population goes through the correctional system at least once. Scarce data are available on circulation of resistant HIV strains in correctional facilities. We evaluated the prevalence of antiretroviral resistance among both naïve and treatment-experienced HIV-infected inmates of a correctional institution in Genoa, Italy. METHOD: The prevalence of antiretroviral resistance among the HIV-infected inmates observed at our institution who underwent genotypic testing from January 2004 to June 2007 was retrospectively reviewed. RESULTS: 45 genotypes from 43 inmates were available. Most of the naïve patients (14/16; 87.5%) showed a wild-type (WT) genotype, as well as most of the ART-experienced patients who had discontinued ART (10/13; 76.9%). A high proportion of WT genotype (6/16; 37.5%) was also observed among the subjects apparently failing HAART. CONCLUSIONS: The prevalence of mutated strains in treatment-naïve individuals of the studied cohort is comparable to what is reported in nonimprisoned naïve subjects of our region. The high prevalence of WT genotypes in ART-failing patients makes it likely that they were not taking their treatments, probably to gain legal benefits from their worsening health conditions. Thus, resistance testing can also be considered as an additional tool for assessing adherence to ART for forensic/medicolegal evaluation. However, further and larger studies are necessary to validate it.