Background: blood cytokines and chemokines have been proposed as biomarkers for tuberculosis (TB). Recently, some immune mediators found in the urine of patients with renal dysfunctions have also been suggested as potential biomarkers. Finding biomarkers for TB in urine would present several advantages over blood in terms of collection and safety. The objective of this study was to investigate the presence of cytokines and chemokines in the urine of patients with pulmonary TB at the time of diagnosis. In a subgroup, the evaluation was also performed during TB treatment and at therapy completion. Patients with lung diseases other than TB, and healthy subjects were also enrolled.Methods: urine samples from 138 individuals, after exclusion of renal dysfunctions, were collected during an 18 month-period. Among them, 58 received a diagnosis of pulmonary TB, 28 resulted having lung diseases other than TB, and 34 were healthy subjects. Moreover, 18 TB patients, 9 of whom were tested 2 months after AFB smear sputum reversion and 9 of whom were cured of TB were also included. Cytokines and chemokines in urine were evaluated using a Cytometric-Bead-Array-Flex-Set. IP-10 detection in 49 subjects was also carried out in parallel by using an Enzyme Linked ImmunoSorbent Assay (ELISA).Results: IFN-γ, TNF-α, IL-2, IL-8, MIP-1α, MIP-1β and RANTES were poorly detected in all urine samples. Conversely, IP-10 was consistently detected in urine and its level was significantly increased in patients with lung disease compared to healthy subjects (p < 0.001). Increased IP-10 levels were found in both pulmonary TB and lung diseases other than TB. Moreover lower IP-10 levels were found in cured-TB patients compared to the levels at the time of diagnosis, and this difference was close to significance (p = 0.06). Interestingly, we demonstrated a significant correlation between the data obtained by flow cytometry and ELISA (r²0.82, p < 0.0001).Conclusions: IP-10, in contrast to IFN-γ, TNF-α, IL-2, IL-8, MIP-1α, MIP-1β and RANTES, is detectable in the urine of patients with pulmonary diseases in the absence of renal dysfunctions. Moreover, the IP-10 level in cured-TB patients is comparable to that found in healthy subjects. More studies are needed to further investigate the clinical utility of these findings.

HIV resistance affects virological response to therapy and efficacy of prophylaxis in mother-to-child-transmission. The study aims to assess the prevalence of HIV primary resistance in pregnant women naïve to antiretrovirals. Cross sectional baseline analysis of a cohort of HIV + pregnant women (HPW) enrolled in the study entitled Antiretroviral Management of Antenatal and Natal HIV Infection (AMANI, peace in Kiswahili language). The AMANI study began in May 2010 in Dodoma, Tanzania. In this observational cohort, antiretroviral treatment was provided to all women from the 28^th week of gestation until the end of the breastfeeding period. Baseline CD4 cell count, viral load and HIV drug-resistance genotype were collected. Drug-resistance analysis was performed on 97 naïve infected-mothers. The prevalence of all primary drug resistance and primary non-nucleoside reverse-transcriptase inhibitors resistance was 11.9% and 7.5%, respectively. K103S was found in two women with no M184V detection. HIV-1 subtype A was the most commonly identified, with a high prevalence of subtype A1, followed by C, D, C/D recombinant, A/C recombinant and A/D recombinant. HIV drug- resistance mutations were detected in A1 and C subtypes. Our study reports an 11.9% prevalence rate of primary drug resistance in naïve HIV-infected pregnant women from a remote area of Tanzania. Considering that the non-nucleoside reverse-transcriptase inhibitors are part of the first-line antiretroviral regimen in Tanzania and all of Africa, resistance surveys should be prioritized in settings where antiretroviral therapy programs are scaled up.

Background/Objectives: Tuberculosis (TB) is preventable and curable, but multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) pose significant challenges worldwide due to the limited treatment options, lengths of therapies, and high rates of treatment failure. The management of MDR-TB has been revolutionized by all oral anti-TB drug regimens that are likely to improve adherence and treatment outcomes. These regimes include bedaquiline (B), pretomanid (P), and linezolid (L) (BPaL), and moxifloxacin if resistance to fluoroquinolones is not detected (BPaLM). Based on the evidence generated by the TB-PRACTECAL and ZeNix randomized controlled trials, BPaL/BPaLM regimens are recommended over the currently recommended longer regimens in patients with MDR-TB or monoresistance to rifampin (RR). To our knowledge, no data are currently available on the implementation of BPaL/BPaLM regimens in Italy. Results: Seventeen patients completed the BPaL/BPaLM regimen, with a treatment success rate of 90% (17/19), consistent with the literature data. Eleven patients out of the nineteen retained in care (58%) complained about symptoms consistent with adverse events (AEs). No treatment interruption was necessary due to AEs. Methods: Here, we report the real-world experience of a tertiary referral hospital for TB in Italy, from 2022 to 2024, in the management, outcomes, and adverse drug reactions of a cohort of twenty-two MDR/RR patients treated with BPaL and BPaLM regimens. Conclusions: BPaL-containing regimens also serve as promising options for patients with RR/MDR-TB in terms of real-life experience, but further multicentric studies are required in Europe to confirm the efficacy of shorter regimens to eliminate MDR TB.

Background/Objectives: Tuberculosis (TB) remains a major global health issue, further complicated by the COVID-19 pandemic. This study assesses the clinical outcomes of TB-COVID-19-coinfected patients compared to those with TB disease alone at an Italian infectious disease hospital during the pandemic’s first two years. Methods: Retrospective data analysis was conducted on TB patients hospitalized from March 2020 to June 2022. Data included demographics, comorbidities, clinical characteristics, and outcomes. Coinfection was defined as concurrent TB disease and SARS-CoV-2 infection. Statistical methods included Fisher’s exact test and Mann–Whitney statistics. Results: Of 267 TB patients, 25 (9.4%) had concurrent COVID-19 infection. The TB-COVID-19 group showed higher rates of diabetes and cough. Acute respiratory failure was more prevalent in coinfected patients (odds ratio, 5.99), and coinfection was associated with worse outcomes compared to TB alone (odds ratio, 0.15). Despite similar socio-demographic factors, the coexistence of TB and COVID-19 led to exacerbated respiratory failure and increased mortality. Conclusions: Coinfection with TB and COVID-19 significantly increases the risk of acute respiratory failure and poor outcomes. Clinicians should be aware of this risk, especially in patients with pulmonary involvement. Although specific protocols are unavailable, prompt diagnosis and management may enhance outcomes. Additional research is necessary to understand the long-term effects of TB-COVID-19 coinfection, particularly as COVID-19 becomes endemic.

Tuberculosis (TB) is still an important cause of morbidity and mortality worldwide. An improvement of the strategies for disease control is necessary in both low- and high-incidence TB countries. Clinicians, epidemiologists, laboratory specialists, and public health players should work together in order to achieve a significant reduction in TB transmission and spread of drug-resistant strains. Effective TB surveillance relies on early diagnosis of new cases, appropriate therapy, and accurate detection of outbreaks in the community, in order to implement proper TB control strategies. To achieve this goal, information from classical and molecular epidemiology, together with patient clinical data need to be combined. In this review, we summarize the methodologies currently used in molecular epidemiology, namely molecular typing. We will discuss their efficiency to phylogenetically characterize Mycobacterium tuberculosis isolates, and their ability to provide information that can be useful for disease control. We will also introduce next generation sequencing as the methodology that potentially could provide in a short time both, detection of new outbreaks and identification of resistance patterns. This could envision a potential of next generation sequencing as an important tool for accurate patient management and disease control.

Diagnosing non-tuberculous mycobacterial pulmonary disease (NTM-PD) in patients unable to produce sputum spontaneously requires invasive procedures to obtain valid respiratory specimens. In this retrospective study, we evaluated the results of microbiological tests performed on respiratory samples of 132 patients affected by NTM-PD. In the diagnostic workout, 98 patients performed both induced sputum (IS) and bronchoalveolar lavage (BAL) and were enrolled in our study. A total of 93 out of 98 BAL samples (95%) were culture-positive for mycobacteria, whereas only 67/153 (44%) induced sputum cultures were positive for NTM (p < 0.001). Molecular identification of NTM with real-time polymerase chain reaction (PCR) was positive in 48/64 BAL (75%) and in 47/139 (34%) IS samples (p < 0.001). Patients affected by nodular-bronchiectatic form were 65/98 (66%): BAL culture was positive in 95% of cases (62/65 BAL), while only 30/99 IS cultures were positive (30%; p < 0.001). PCR was positive in 76% of BAL samples examined (26/34) and in 26% of the IS samples (24 out of 91) (p < 0.001). Among 33 patients with a fibro-cavitary radiological pattern, 65% of IS (35/54) were culture-positive for NTM, whereas 94% of cases (31/33) had a positive culture for NTM from BAL (p = 0.002). PCR was positive in 73% of BAL samples tested (22/30) and 48% of IS samples tested (23/48) (p = 0.031). Our results confirm BAL mycobacterial culture as the gold standard for the diagnosis of pulmonary mycobacteriosis. FBS with BAL should be performed in every patient with a strong suspicion of NTM-PD, if other respiratory samples are repeatedly negative. Sputum induction is a useful technique to obtain valid respiratory samples when patients are unable to produce spontaneous sputum, especially in the outpatient setting. However, during the diagnostic workup of NTM-PD, we should not forget that PCR and mycobacterial culture of induced sputum have a lower yield than when performed on BAL, especially in the nodular-bronchiectatic form of the disease.