Lysosomal enzymes and the oxygen burst capability of monocyte-derived macrophages in active drug-resistant tuberculosis patients in relation to cell attachment.

Drug resistance to tuberculosis (TB) has become an obstacle in eliminating tuberculosis. The transmission of drug-resistant TB from patients increases the incidence of primary drug-resistant (DR) TB in individuals who are in close contact. Therefore, it is necessary to incorporate an immunological approach into preventive therapy. This study focuses on the activity of lysosomal enzymes, oxygen bursts, and the attachment ability of macrophages among individuals diagnosed with active drug-resistant TB compared with close contacts with latent TB or healthy cases. We measured macrophage oxygen burst ability (Water-soluble tetrazolium salt (WST) test, Nitric Oxide production, and myeloperoxidase activity) and the degradative ability of lysosomes (activity of the ß-glucuronidase and acid phosphatase enzymes). Six active DR-TB patients and 18 close-contact cases (8 Latent Tuberculosis Infection (LTBI); 10 healthy) were recruited at Universitas Indonesia Hospital. The macrophage attachment of the LTBI group was higher than in the other groups. NO production, myeloperoxidase activity, ß-glucuronidase, and acid phosphatase were higher in the active DR-TB group. A negative correlation was uncovered between phagocytosis and NO production, myeloperoxidase activity, and lysosomal enzymes. The difference in macrophage function is expected to be a further reference in active DR-TB treatment or preventive therapy.

Clinical presentation, management, and outcome of suspected central nervous system infections in Indonesia: a prospective cohort study.

BACKGROUND: Little is known about the etiology, clinical presentation, management, and outcome of central nervous system (CNS) infections in Indonesia, a country with a high burden of infectious diseases and a rising prevalence of HIV. METHODS: We included adult patients with suspected CNS infections at two referral hospitals in a prospective cohort between April 2019 and December 2021. Clinical, laboratory, and radiological assessments were standardized. We recorded initial and final diagnoses, treatments, and outcomes during 6 months of follow-up. RESULTS: Of 1051 patients screened, 793 were diagnosed with a CNS infection. Patients (median age 33 years, 62% male, 38% HIV-infected) presented a median of 14 days (IQR 7-30) after symptom onset, often with altered consciousness (63%), motor deficits (73%), and seizures (21%). Among HIV-uninfected patients, CNS tuberculosis (TB) was most common (60%), while viral (8%) and bacterial (4%) disease were uncommon. Among HIV-infected patients, cerebral toxoplasmosis (41%) was most common, followed by CNS TB (19%), neurosyphilis (15%), and cryptococcal meningitis (10%). A microbiologically confirmed diagnosis was achieved in 25% of cases, and initial diagnoses were revised in 46% of cases. In-hospital mortality was 30%, and at six months, 45% of patients had died, and 12% suffered from severe disability. Six-month mortality was associated with older age, HIV, and severe clinical, radiological and CSF markers at presentation. CONCLUSION: CNS infections in Indonesia are characterized by late presentation, severe disease, frequent HIV coinfection, low microbiological confirmation and high mortality. These findings highlight the need for earlier disease recognition, faster and more accurate diagnosis, and optimized treatment, coupled with wider efforts to improve the uptake of HIV services.

Adjunctive Dexamethasone for Tuberculous Meningitis in HIV-Positive Adults.

BACKGROUND: Adjunctive glucocorticoids are widely used to treat human immunodeficiency virus (HIV)-associated tuberculous meningitis despite limited data supporting their safety and efficacy. METHODS: We conducted a double-blind, randomized, placebo-controlled trial involving HIV-positive adults (≥18 years of age) with tuberculous meningitis in Vietnam and Indonesia. Participants were randomly assigned to receive a 6-to-8-week tapering course of either dexamethasone or placebo in addition to 12 months of antituberculosis chemotherapy. The primary end point was death from any cause during the 12 months after randomization. RESULTS: A total of 520 adults were randomly assigned to receive either dexamethasone (263 participants) or placebo (257 participants). The median age was 36 years; 255 of 520 participants (49.0%) had never received antiretroviral therapy, and 251 of 484 participants (51.9%) with available data had a baseline CD4 count of 50 cells per cubic millimeter or less. Six participants withdrew from the trial, and five were lost to follow-up. During the 12 months of follow-up, death occurred in 116 of 263 participants (44.1%) in the dexamethasone group and in 126 of 257 participants (49.0%) in the placebo group (hazard ratio, 0.85; 95% confidence interval, 0.66 to 1.10; P = 0.22). Prespecified analyses did not reveal a subgroup that clearly benefited from dexamethasone. The incidence of secondary end-point events, including cases of immune reconstitution inflammatory syndrome during the first 6 months, was similar in the two trial groups. The numbers of participants with at least one serious adverse event were similar in the dexamethasone group (192 of 263 participants [73.0%]) and the placebo group (194 of 257 participants [75.5%]) (P = 0.52). CONCLUSIONS: Among HIV-positive adults with tuberculous meningitis, adjunctive dexamethasone, as compared with placebo, did not confer a benefit with respect to survival or any secondary end point. (Funded by the Wellcome Trust; ACT HIV ClinicalTrials.gov number, NCT03092817.).

Porphyromonas gingivalis association with inflammatory markers and exosomal miRNA-155 in saliva of periodontitis patients with and without diabetes diagnosed with COVID-19.

Background: /Purposes: Studies have indicated that salivary molecules from patients with periodontitis and diabetes are confounded with pathological conditions associated with SARS-CoV-2 infection. The study aimed to address whether the abundance of Porphyromonas gingivalis which causes periodontitis, differed compared with that of Aggregatibacter actinomycetemcomitans (used as control) and to analyze the correlation of periodontitis with the expression levels of severe acute respiratory syndrome coronavirus 2 receptor (ACE2) and periodontitis inflammatory markers (TLR-2/TLR-4, TNFα, and miR-155). Materials and Methods: A saliva sample (5 mL) was obtained from 23 hospitalized patients with COVID-19, categorized into two groups: diabetic (G1, n = 10) and non-diabetic (G2, n = 13). Saliva from patients with periodontitis without diabetes and coronavirus disease 2019 (COVID-19; n = 6) were included as control. The quantitative real-time polymerase chain reaction measured the levels of P. gingivalis and A. actinomycetemcomitans, as well as periodontitis markers in saliva. The obtained data were analyzed using one-way ANOVA and the Spearman correlation test. Results: The abundance of P. gingivalis was observed to be higher (p < 0.05) in saliva of patients with diabetes (G1) than in those without diabetes (G2). A contradictory trend was observed for A. actinomycetemcomitans. The transcription level of ACE2 was comparable in all groups tested, while the expression of periodontitis markers varied. The relationships and sensitivity/specificity among P. gingivalis infection ACE2 expression, and inflammatory markers were also evaluated. Conclusions: This study showed that the association between P. gingivalis infection and ACE2 expression might reflect the characteristics of saliva in COVID-19 patients with and without diabetes. However, the relationships between TLR-4 and miR-155 are more specific in discriminating against COVID-19 patients with and without diabetes.

The utility of salivary CRP and IL-6 as a non-invasive measurement evaluated in patients with COVID-19 with and without diabetes.

Background: The available evidence suggests that inflammatory responses, in both systemic and oral tissue, contribute to the pathology of COVID-19 disease. Hence, studies of inflammation biomarkers in oral fluids, such as saliva, might be useful to better specify COVID-19 features. Methods: In the current study, we performed quantitative real-time PCR to measure salivary levels of C-reactive protein (CRP) and interleukin-6 (IL-6) in saliva obtained from patients diagnosed with mild COVID-19, in a diabetic group (DG; n = 10) and a non-diabetic group (NDG; n = 13). All participants were diagnosed with periodontitis, while six participants with periodontitis but not diagnosed with COVID-19 were included as controls. Results: We found increases in salivary total protein levels in both the DG and NDG compared to control patients. In both groups, salivary CRP and IL-6 levels were comparable. Additionally, the levels of salivary CRP were significantly correlated with total proteins, in which a strong and moderate positive correlation was found between DG and NDG, respectively. A linear positive correlation was also noted in the relationship between salivary IL-6 level and total proteins, but the correlation was not significant. Interestingly, the association between salivary CRP and IL-6 levels was positive. However, a moderately significant correlation was only found in COVID-19 patients with diabetes, through which the association was validated by a receiver operating curve. Conclusions: These finding suggest that salivary CRP and IL-6 are particularly relevant as potential non-invasive biomarker for predicting diabetes risk in mild cases of COVID-19 accompanied with periodontitis.