Search Results (73)

Tuberculosis is an infectious condition caused by Mycobacterium tuberculosis, primarily targeting the pulmonary system, with the potential to disseminate to various other organs via the haematogenous pathway, ranking among the top ten causes of global mortality. Tuberculosis remains a serious public health problem worldwide. This narrative review aims to emphasise the clinical importance of the inter-relationships between nutrition, pharmacotherapy, and the most common drug–nutrient interactions in the context of tuberculosis and multi-drug-resistant tuberculosis management. Nowadays, pharmacologic approaches utilise polytherapeutic regimens that, although showing increased efficacy, prominently affect the nutritional status of patients and modify multiple metabolic pathways, thus influencing both the effectiveness of therapy and the patient outcomes. There is much evidence that antituberculosis drugs are associated with deficiencies in essential vitamins and various micronutrients, leading to serious adverse consequences. Moreover, poor nutrition exacerbates TB outcomes, and TB further exacerbates nutritional status, a vicious cycle that is particularly prevalent in low-resource environments. Nutritional support is necessary, and clinicians ought to evaluate it on a patient-by-patient basis, as empirical evidence has shown that it can improve immune recovery, decrease tuberculosis-associated morbidity, and increase adherence to therapy. However, drug–food interactions are increasingly prevalent, and patients with tuberculosis require personalised dietary and pharmacological regimens. In this context, antituberculosis treatment requires a holistic approach, based on the collaboration of the prescribing physician, pharmacist, and nutritionist, to assess the patient’s needs from a nutritional and pharmacological perspective, with the ultimate goal of decreasing mortality and improving the prognosis of patients through personalised therapies. Full article

Background: This case is unique in demonstrating the reactivation of latent tuberculosis (TB) following co-infection with SARS-CoV-2 and Epstein–Barr virus (EBV) in an otherwise healthy young adult. It highlights a rare clinical scenario in which viral immune dysregulation likely facilitated TB progression. To date, few reports have explored the complex interplay between COVID-19, EBV reactivation, and TB in a single patient, particularly with isolated extrapulmonary involvement. Case Presentation: A 24-year-old woman presented with persistent low-grade fever, fatigue, night sweats, unintentional weight loss, and progressive cervical and supraclavicular lymphadenopathy. These symptoms emerged shortly after a moderate COVID-19 infection. Laboratory studies revealed elevated inflammatory markers and pronounced lymphopenia. EBV reactivation was confirmed via serology and PCR. Despite antiviral therapy, symptoms persisted, and imaging revealed necrotic lymphadenopathy. Tuberculous lymphadenitis was diagnosed through fine-needle aspiration cytology and PCR detection of Mycobacterium tuberculosis. The patient was treated with a standard anti-tuberculosis regimen, resulting in clinical, radiological, and immunological improvement. Conclusions: This case underscores the importance of considering latent TB reactivation in patients with persistent lymphadenopathy and recent viral infections, particularly in regions with high TB prevalence. It also emphasizes the need for thorough immunological and microbiological assessment in complex post-viral syndromes. The main clinical takeaway is that COVID-19 and EBV co-infection may create a permissive environment for TB reactivation through immune system compromise. Full article

Background: The appearance of new clinical manifestations (for example, subcutaneous or skin abscesses) during anti-tuberculosis treatment is generally indicative of therapeutic failure. The cause of therapeutic failure may be the presence of a drug-resistant Mycobacterium infection or to the failure to achieve a sufficient concentration of the drugs in the bloodstream. Case report: Here, we report the case of a 25-year-old man suffering from tuberculosis infection with lymph-node and pulmonary involvement and an atypical response to specific therapy. Two weeks after starting four-drug antitubercular treatment, the patient began to experience fever, pain and functional impotence in the left foot and ankle, with subsequent evidence of ankle and tarsal osteomyelitis. Four weeks after starting treatment, the patient presented with several widespread, painful subcutaneous abscesses on the trunk, back and right lower limb. Drainage was performed from the ankle and from one of the abscesses, and polymerase chain reaction (PCR) showed a positive result for M. tuberculosis in both samples, with the absence of resistance to drugs. Anti-tubercular medications were continued, with resolution of the pulmonary and bone involvement but with persistence of subcutaneous abscesses, although subsequent drainages showed the absence of mycobacterium tuberculosis. Conclusions: We describe an unusual presentation of paradoxical reaction in the form of osteomyelitis and subcutaneous abscesses in an immunocompetent TB patient, and we reported other similar cases of paradoxical reactions described in the literature in the last ten years, which demonstrate the importance of considering paradoxical reactions in patients who present with new or worsening signs and symptoms after starting tuberculosis treatment. Full article

Sarcoidosis is a rare multisystem inflammatory disease characterized by non-necrotizing granulomas, typically affecting the lungs, lymph nodes, skin, and bones. Due to its extreme clinical heterogeneity, diagnosis remains challenging. Within the skeletal system, the thoracic spine, ankles, and knees are the most commonly involved joints. We report a rare case of non-articular osseous sarcoidosis with progressive pulmonary lesions and persistently normal inflammatory biomarkers (ACE, CRP, ESR, IL-2, and TNF-α) that required differentiation from metastatic bone tumors and tuberculosis. Prior to presentation at our hospital, the patient did not respond to six months of anti-tuberculosis treatment and one month of systemic glucocorticoid therapy in three other hospitals. Based on lung and bone biopsies, she was finally diagnosed as having active sarcoidosis in our hospital. Despite 3 months of prednisone, pulmonary consolidation and bone lesions persisted until methotrexate was added. This case highlights the preference of combined glucocorticoid and methotrexate therapy for sarcoidosis with atypical osseous involvement and normal biomarkers, underscoring the urgent need for novel diagnostic tools to mitigate misdiagnosis. Full article

Antituberculosis drug-induced hepatotoxicity (ATDH) is a common adverse drug reaction often requiring treatment interruption, complicating tuberculosis management. The slow acetylator phenotype, characterized by reduced N-acetyltransferase 2 (NAT2) enzyme activity, is associated with increased hepatotoxicity risk, while rapid acetylators are associated with a higher risk of therapeutic failure. This study investigates the association between the NAT2 acetylation phenotype and ATDH occurrence, with an emphasis on its predictive value in regard to a multiethnic population and its impact on the timing of ATDH onset. A retrospective observational study was conducted on tuberculosis patients treated at Luigi Sacco Hospital, Milan, Italy (July 2020–September 2023). The NAT2 genotyping identified slow and rapid/intermediate acetylators. Cumulative incidence analysis and Fine–Gray competing risks regression models were used to assess ATDH risk and onset timing. Among 102 patients, 21.6% developed ATDH, including 16.7% with slow and 4.9% with rapid/intermediate acetylators. ATDH onset was significantly earlier in regard to slow acetylators (median 0.5 vs. 2 months, interquartile range-IQR: 0.5–3 vs. 1.7–5.5). Slow acetylators were associated with a higher risk of developing ATDH (Sub-distribution hazard ratio, SHR = 3.05; 95% confidence interval-CI: 1.17–7.95; p = 0.02), even after adjusting for confounders. The NAT2 acetylation phenotype strongly influences ATDH risk and timing. Early acetylator status identification may enable dose adjustments, enhancing treatment safety. These findings highlight the role of pharmacogenetics in optimizing antituberculosis therapy by improving efficacy and minimizing toxicity. Full article

In 2022, the World Health Organization reported that tuberculosis (TB) was the second leading cause of death globally from a single infectious agent following COVID-19. The development of new antitubercular agents with novel mechanisms of action for use in complex TB therapy is considered a key approach to combating TB. In this study, we examined the gene expression profile of M. smegmatis when exposed to a promising antituberculosis agent, quinoxaline 1,4-dioxide (QdNO) 7-chloro-2-(ethoxycarbonyl)-3-methyl-6-(piperazin-1-yl)quinoxaline-1,4-dioxide-1 (LCTA-3368). We investigated how the bacterial response changed with different minimum inhibitory concentrations (MIC) (1/4 × MIC, 1/2 × MIC, and 1 × MIC) and durations (30 min and 90 min) of treatment with the drug. Our analysis revealed significant upregulation in genes involved in DNA repair and replication processes, as well as changes in the expression of 95 genes encoding proteins with oxidoreductase activity. We additionally showed that the concentration of reactive oxygen species increases in a dose-dependent manner upon exposure of M. smegmatis to LCTA-3368. These findings support the proposed mechanism of antibacterial action of QdNOs, which is associated with the formation of free radicals leading to DNA damage. Full article

We describe the case of a 67-year-old man with lung cancer, who developed pulmonary tuberculosis (TB) following chemotherapy and subsequently exhibited a paradoxical reaction on positron emission tomography/computed tomography (PET/CT) after initiating antituberculosis therapy. While pulmonary consolidations improved with antituberculosis treatment, newly detected hypermetabolic mediastinal lymph nodes appeared on PET/CT. Based on the clinical course, we provisionally concluded that the mediastinal lymphadenopathy represented a paradoxical reaction. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) confirmed the diagnosis of TB. Clinicians added steroids and continued the antituberculosis medication, and follow-up PET/CT showed complete resolution of these lesions. This case highlights the importance of recognizing paradoxical reactions to antituberculosis therapy, when restaging PET/CT reveals divergent findings, with some tumor foci responding and other lesions appearing to be progressing. Full article

Extensive research on tuberculosis (TB) and HIV co-infection reveals the diverse prevalence and co-epidemic patterns across populations, necessitating tailored public health strategies. Co-infection is bidirectional; individuals with HIV are more susceptible to TB, and vice versa. Antiretroviral therapy (ART) and antituberculosis treatment (ATT) are critical for managing these conditions, but pose risks due to drug–pathogen and drug–drug interactions, potentially leading to immune reconstitution inflammatory syndrome (IRIS) in patients with HIV/AIDS. IRIS, often triggered by highly active antiretroviral therapy (HAART), can exacerbate HIV progression, increase drug resistance, and deteriorate patients’ quality of life. Approximately one-third of the global population with HIV is also infected with TB, with extensive drug-resistant (XDR) and multidrug-resistant (MDR) strains posing significant challenges. Latent TB infection (LTBI) further complicates the scenario, as it can progress to active TB, particularly in individuals with both conditions. The global and Indian mortality rates for TB-HIV co-infection remain high, emphasizing the need for new strategies. Additionally, unreported cases and inadequate post-treatment monitoring contribute to the high mortality rate, particularly among patients with LTBI. The complexity of managing HIV-TB co-infection, especially with LTBI, underscores the urgency of addressing these challenges to improve the outcomes for the affected populations. Full article

The current 2019–2021 marine pharmacology literature review provides a continuation of previous reviews covering the period 1998 to 2018. Preclinical marine pharmacology research during 2019–2021 was published by researchers in 42 countries and contributed novel mechanism-of-action pharmacology for 171 structurally characterized marine compounds. The peer-reviewed marine natural product pharmacology literature reported antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral mechanism-of-action studies for 49 compounds, 87 compounds with antidiabetic and anti-inflammatory activities that also affected the immune and nervous system, while another group of 51 compounds demonstrated novel miscellaneous mechanisms of action, which upon further investigation, may contribute to several pharmacological classes. Thus, in 2019–2021, a very active preclinical marine natural product pharmacology pipeline provided novel mechanisms of action as well as new lead chemistry for the clinical marine pharmaceutical pipeline targeting the therapy of several disease categories. Full article

There are more than 170 known species of non-tuberculous mycobacteria, and some are responsible for serious diseases in people infected with them. One of these is Buruli ulcers, a neglected tropical disease endemic in more than 33 countries and caused by Mycobacterium ulcerans, which infects skin tissue. Treatment consists of a long-term regimen combining the use of oral rifampin with another anti-tuberculosis drug (e.g., clarithromycin). Patients in these countries face difficulties in accessing and adhering to this therapy. This study investigates the feasibility of formulating stable, optimized clarithromycin as a topical cutaneous cream. The cream was formulated, and its stability was evaluated under different storage temperature conditions and using a stability indicator method. The results showed that the clarithromycin cream was stable for at least 60 days, even at extreme temperatures (40 °C). In conclusion, the data presented here demonstrate the stability of a new form of topical cutaneous clarithromycin, which may offer a new approach to the treatment of Buruli ulcers and clarithromycin-sensitive infections. Full article

Chronic immune activation in tuberculosis (TB) associated with human immunodeficiency virus (HIV) infection (HIV/TB) modifies their clinical course. We prospectively measured osteopontin (OPN), full-length galectin-9 (FL-Gal9), and total-Gal9 (T-Gal9) levels in 32 patients with HIV/TB coinfection treated with anti-tuberculosis and antiretroviral therapies over 6–18 months to determine the amelioration of inflammatory conditions in response to the therapies. We observed a significant time-dependent decrease in FL-Gal9 in both pulmonary TB (PTB, n = 20) and extrapulmonary TB (EPTB, n = 12) patients. The levels of T-Gal9, OPN, and CRP decreased significantly after treatment in only PTB patients. We calculated the inflammatory score (INS) indicating immunologic recovery based on the decline in OPN, FL-Gal9, T-Gal9, and CRP levels. Baseline levels of T-Gal9 and OPN positively correlated with INS in all TB and only PTB patients, respectively, indicating that their levels predict better recovery. In contrast, FL-Gal9 levels at the second visit negatively correlated with INS in EPTB patients. The decrease rate in OPN levels at the second visit also correlated positively with INS in PTB patients. Women showed a higher INS and lower levels of FL-Gal9 than men. The patients with moderate grade severity on chest X-ray had higher CD4 cell numbers than those with limited grade severity. Monitoring these markers will help to predict and assess the response to therapy as well as to devise strategies to reduce the complications caused by chronic immune activation in patients with HIV/TB coinfection. Full article

We present a new category of quinoxaline di-N-oxides (QdNOs) containing amino acid side chains with dual antituberculosis and antileishmanial activity. These compounds were synthesized by combining a regioselective 2,5-piperazinedione opening and a Beirut reaction and were screened for their activity against Mycobacterium tuberculosis and the promastigote and amastigote forms of representative species of the Leishmania genus. Most QdNOs exhibited promising antitubercular activity with IC₅₀ values ranging from 4.28 to 49.95 μM, comparable to clinically established drugs. Structure–activity relationship analysis emphasized the importance of substituents on the aromatic ring and the side chain. Antileishmanial tests showed that some selected compounds exhibited activity comparable to the positive control miltefosine against promastigotes of Leishmania amazonensis and Leishmania donovani. Notably, some compounds were found to be also more potent and less toxic than miltefosine in intracellular amastigote assays against Leishmania amazonensis. The compound showing the best dual antitubercular and leishmanicidal profile and a good selectivity index, 4h, can be regarded as a hit compound that opens up new opportunities for the development of integrated therapies against co-infections. Full article

Tuberculosis is one of the most common opportunistic infections and a prominent cause of death in patients with human immunodeficiency virus (HIV) infection, in spite of near-universal access to antiretroviral therapy (ART) and tuberculosis preventive therapy. For patients with active tuberculosis but not yet receiving ART, starting ART after anti-tuberculosis treatment can complicate clinical management due to drug toxicities, drug–drug interactions and immune reconstitution inflammatory syndrome (IRIS) events. The timing of ART initiation has a crucial impact on treatment outcomes, especially for patients with tuberculous meningitis. The principles of ART in patients with HIV-associated tuberculosis are specific and relatively complex in comparison to patients with other opportunistic infections or cancers. In this review, we summarize the current progress in the timing of ART initiation, ART regimens, drug–drug interactions between anti-tuberculosis and antiretroviral agents, and IRIS. Full article

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains a global health crisis with substantial morbidity and mortality rates. Type II alveolar epithelial cells (AEC-II) play a critical role in the pulmonary immune response against Mtb infection by secreting effector molecules such as antimicrobial peptides (AMPs). Here, human β-defensin 1 (hBD1), an important AMP produced by AEC-II, has been demonstrated to exert potent anti-tuberculosis activity. HBD1 overexpression effectively inhibited Mtb proliferation in AEC-II, while mice lacking hBD1 exhibited susceptibility to Mtb and increased lung tissue inflammation. Mechanistically, in A549 cells infected with Mtb, STAT1 negatively regulated hBD1 transcription, while CEBPB was the primary transcription factor upregulating hBD1 expression. Furthermore, we revealed that the ERK1/2 signaling pathway activated by Mtb infection led to CEBPB phosphorylation and nuclear translocation, which subsequently promoted hBD1 expression. Our findings suggest that the ERK1/2-CEBPB-hBD1 regulatory axis can be a potential therapeutic target for anti-tuberculosis therapy aimed at enhancing the immune response of AEC-II cells. Full article

Accumulating evidence show a potential association between tuberculosis and COVID-19 disease severity. To further clarify the impact of tuberculosis on COVID-19 disease severity and viral shedding duration, a retrospective study was conducted on 223 COVID-19 patients, including 34 with tuberculosis and 189 without tuberculosis. Clinical information and viral load shedding time were collected. A higher percentage of severe/critical COVID-19 diagnosis and deaths was observed in patients with tuberculosis than in those without tuberculosis (8.8% vs. 3.2%, p = 0.142; 2.9% vs. 1.1%, p = 0.393), and COVID-19 patients with tuberculosis had longer viral shedding than those without tuberculosis (median: 15.0 days vs. 11.0 days; p = 0.0001). Having tuberculosis (HR = 2.21, 95% CI 1.37–3.00; p = 0.000), being of elderly age (HR = 1.02, 95% CI 1.01–1.03; p = 0.001) and being diagnosed with severe or critical COVID-19 (HR = 5.63, 95% CI 2.10–15.05; p = 0.001) were independent factors associated with prolonged virus time of SARS-CoV-2. COVID-19 patients with tuberculosis receiving anti-tuberculosis therapy time (ATT) for <2 months had a significantly longer virus shedding duration than those receiving ATT for ≥ 4 months (17.5 vs. 11.5 days, p = 0.012). Our results demonstrated that COVID-19 patients with tuberculosis tend to have more severe disease and a worse prognosis, and tuberculosis prolonged viral shedding, highlighting special attention and/or care required for COVID-19 patients with tuberculosis receiving ATT for <2 months. Full article