Multidrug-resistant tuberculosis.

One of predominant contributors to global mortality is tuberculosis (TB), an infection caused by Mycobacterium tuberculosis (MTB). Inappropriate and ineffectual treatment can lead to the development of drug-resistant TB. One of the most common forms of drug-resistant TB is multidrug-resistant tuberculosis (MDR-TB), caused by mutations in the rpoB and katG genes that lead to resistance to anti-TB drugs, rifampicin (RIF) and isoniazid (INH), respectively. Although culturing remains the gold standard, it is not rapid thereby delaying potential treatment and potentially increasing the incidence of MDR-TB. In contrast, molecular techniques provide a highly sensitive and specific alternative. This review discusses the classification of biomarkers used to detect MDR-TB, some of the commonly used anti-TB drugs, and DNA mutations in MTB that lead to anti-TB resistance. The objective of this review is to increase awareness of the need for rapid and precise detection of MDR-TB cases to decrease morbidity and mortality of this infectious disease worldwide.

Insights from the molecular mechanism of pyrazinamide to mutated pyrazinamidase linked to the pncA gene in clinical isolates of Mycobacterium tuberculosis.

This study aims to conduct a comprehensive molecular dynamics strategy to evaluate whether mutations found in pyrazinamide monoresistant (PZAMR) strains of Mycobacterium tuberculosis (MTB) can potentially reduce the effectiveness of pyrazinamide (PZA) for tuberculosis (TB) treatment. Five single point mutations of pyrazinamidase (PZAse), an enzyme which is responsible for the activation of prodrug PZA into pyrazinoic acid, found in MTB clinical isolates, namely His82Arg, Thr87Met, Ser66Pro, Ala171Val, and Pro62Leu, were analyzed by the dynamics simulations both in the apo state (unbound state) and in the PZA bound state. The results showed that the mutation of His82 to Arg, Thr87 to Met, and Ser66 to Pro in PZAse affects the coordination state of the Fe2+ ion, which is a cofactor required for enzyme activity. These mutations change the flexibility, stability, and fluctuation of His51, His57, and ASP49 amino acid residues around the Fe2+ ion, culminating in an unstable complex and dissociation of PZA from the PZAse binding site. However, mutations of Ala171 to Val and Pro62 to Leu were found to have no effect on the complex's stability. Based on the results, PZAse mutations of His82Arg, Thr87Met, and Ser66Pro culminated in weak binding affinity for PZA and caused significant structural deformations that led to PZA resistance. Future structural and functional studies, as well as investigations into other aspects of drug resistance in PZAse, will require experimental clarification.Communicated by Ramaswamy H. Sarma.

Development and validation of assessment instrument for the perception and attitude toward tuberculosis among the general population in Indonesia: a Rasch analysis of psychometric properties.

Introduction: Tuberculosis (TB)-related knowledge is an important evaluation metric for health education interventions. Factor analysis is limited when used on ordinal scales and does not provide in-depth item function examinations, whereas Rasch analysis addresses these limitations and offers potential advantages such as generalizability, testing of unidimensionality, producing an ordered set of items, and identifying poorly functioning items. Therefore, this research aims to develop a reliable and valid measure of perception and attitude toward TB (PATT) for public application use Rasch Analysis. Methods: A questionnaire-based survey was conducted on the Indonesian general population using the Google Form platform. Rasch analysis was then employed to examine the psychometric properties and develop the final items of PATT. Results: Experts from across the TB community participated in the PATT development, producing an initial scale of 16 items. Up to 1,616 participants completed the PATT questionnaire, where 74.8% were female, and 5% had a TB history. The final unidimensional 16-item scale has an item reliability of 1.00 for the two components (perception and attitude), a person reliability index of 0.87 and 0.60, as well as a Cronbach's test reliability of 0.88 and 0.88 for perception and attitude, respectively. Conclusion: The PATT is a unidimensional scale with good construct validity and internal consistency. It has the potential to be useful for the assessment of TB perception and attitude in research and clinical practice.

Development and Validation of Questionnaire to Measure Parents' Knowledge, Attitude, and Practice on Self-Medication of Children with Antibiotics in Bandung, Indonesia.

Purpose: This study aimed to develop and validate a questionnaire to measure the knowledge, attitude, and practice of parents regarding antibiotic use in Indonesian children using structural equation modeling (SEM) analysis. Methods: The instrument development process was conducted from January 5 to 19, 2023, using the following steps: 1) literature review and item development, 2) internal review and refinement, 3) structural model analysis, and 4) measurement models' reliability and validity. A convenience sample was used to recruit parents as participants from Arcamanik District, Bandung, Indonesia. A total of 83 respondents completed the on-site interview questionnaire. Furthermore, statistical analyses were performed using SPSS Version 21.0 and Analysis of Moment Structures (AMOS) Version 26.0. Results: The content validity for the scales was over 50%, and the reliabilities for the 38 items of the questionnaire were above 0.6, respectively. The suitability of the model was assessed, and the findings showed parameters for indicators: chi-square = 0.0004, CFI = 0.977, RMSEA = 0.044, CMIN/DF = 1.162, AGFI = 0.651, TLI = 0.973, and NFI = 0.860. The GFI parameter did not fit with the output value of 0.718, while the convergent and divergent validity of scores provided evidence in the expected direction. Conclusion: This psychometric development study provides preliminary evidence that the 38-item scales were reliable and valid for assessing knowledge, attitude, and practice toward parents in the self-medication of antibiotics in children.

Epitope-based vaccine design against the membrane and nucleocapsid proteins of SARS-CoV-2.

BACKGROUND: The high prevalence and mortality rate of coronavirus disease 2019 (COVID-19) is a major global concern. Bioinformatics approaches have helped to develop new strategies to combat infectious agents, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Indeed, the structural proteins of microorganisms provide suitable epitopes for the development of vaccines to prevent infectious diseases. OBJECTIVES: The present study aimed to use bioinformatics tools to find peptides from the membrane (M) and nucleocapsid (N) proteins with effective cellular and humoral immunogenicity. MATERIAL AND METHODS: Sequences of the M and N proteins were sourced from the National Center for Biotechnology Information (NCBI). The conserved regions of the proteins with the highest immunogenicity were identified and assessed using different servers, and the physicochemical and biochemical properties of the epitopes were evaluated. Finally, allergenicity, antigenicity and docking to human leukocyte antigen (HLA) were investigated. RESULTS: The data indicated that the best epitopes were LVIGFLFLT and LFLTWICLL (as membrane epitopes), and KLDDKDPNFKDQ (as a nucleocapsid epitope), with significant immunogenicity and no evidence of allergenicity. The 3 epitopes are stable peptides that can interact with HLA to induce strong immune responses. CONCLUSIONS: The findings indicate that 3 common epitopes could effectively elicit an immune response against the disease. Hence, in vitro and in vivo studies are recommended to confirm the theoretical information.

Knowledge, perceptions, and readiness of telepharmacy (KPR-TP) questionnaire among pharmacists: Development and psychometric evaluation.

INTRODUCTION: The pandemic increased pressure on healthcare services and forced limited care in all health facilities to ensure the care of all patients. Telepharmacy appears as an alternative to the remote pharmacy practice approach through information and communication technologies, but there are no comprehensive tools to measure pharmacists' knowledge, perception, and readiness to implement telepharmacy. This study developed and validated a questionnaire version of the Knowledge, Perceptions, and Readiness of Telepharmacy (KPR-TP) for pharmacists. METHODS: The KPR-TP assessed three domains: knowledge, perception, and readiness. Its factor structure, reliability, and validity were assessed using 7730 pharmacists from 34 Indonesian provinces. The validity of the model's three-factor structure was assessed using confirmatory factor analysis. Cronbach's alpha and composite reliability were used to validate the consistency of our factors, whereas convergent and discriminant validity established significant relationships between them. RESULTS: The goodness-of-fit index indicated that the model was economical and reasonable. Furthermore, the correlation between the three domains revealed a significant positive relationship. KRP-TP is a viable instrument for assessing pharmacists' perceptions of telepharmacy in Indonesia. CONCLUSION: Overall, we discovered that our questionnaire contains critical constructs for assessing a pharmacist's knowledge, perception, and level of readiness to implement telepharmacy. This study will help pharmacists identify appropriate strategies for skill improvement.

Rasch Modelling to Assess Psychometric Validation of the Knowledge about Tuberculosis Questionnaire (KATUB-Q) for the General Population in Indonesia.

OBJECTIVE: This study aims to validate and evaluate the psychometric properties of the knowledge about tuberculosis questionnaire (KATUB-Q) for the general population in Indonesia. METHODS: The KATUB-Q consists of three domains: general knowledge, transmission, and treatment, with 20 dichotomous items. Rasch analysis through WINSTEPS was used. RESULTS: A total of 504 respondents from 34 provinces in Indonesia completed the survey. Based on the model fit statistics, 3 misfit items were deleted and 17 items were used. Item and person reliability, as well as Cronbach's Alpha values were 0.99, 0.63, and 0.73, respectively, which means they achieved the minimum acceptable limit of 0.6. Based on the results, Indonesia's Person ability analysis indicated a high level of knowledge. KATUB-Q has no significant bias item based on sex found in the differential item functioning analysis. CONCLUSION: KATUB-Q has 17 items with a valid and reliable instrument; hence, it can be used to measure the knowledge about TB in the general population. PRACTICE IMPLICATIONS: The unidimensional structure of the core items of the KATUB-Q provides empirical evidence for using the sum score of the items in practice to evaluate the effectiveness of TB education in the general population.

Herbal Therapy for the Treatment of Seborrhea Dermatitis.

Seborrhea dermatitis is a skin disorder that usually appears on parts of the body that have high density of sebaceous glands, such as the face, chest, and scalp. Clinical manifestations that generally appear as scaly skin and erythema. Seborrhea dermatitis is also known as one of the causes of alopecia. Treatments that can be used for seborrhea dermatitis are antifungal, anti-inflammatory, keratolytic, and coal tar. There are concerns about poor adherence, resistance, and some side effects of drugs that have been used in the treatment of seborrhea dermatitis. Concerns regarding these issues increase the urgency for the development of new therapeutic agents in the treatment of seborrhea dermatitis. Research on medicinal plants has enormous potential to produce compounds with new structures and bioactivity. This review discusses clinical and in vitro studies related to the activity of several medicinal plants that have potential as a treatment for seborrhea dermatitis, as well as the compounds that play a role in these activities. Literature searches were carried out on the PubMed, Taylor & Francis, and SpringerLink databases using Boolean Operators to get 25 articles that match the keywords used. Of the 25 articles, six were clinical trials, while 19 were in vitro studies of Malassezia. Several plants have potential as promising therapeutic agents for the treatment of seborrhea dermatitis by inhibiting the growth of Malassezia, decreasing sebum secretion, and decreasing symptoms associated with seborrhea dermatitis such as itching, pain or burning sensation, and redness.

Role of Pharmacists in Antimicrobial Stewardship During COVID-19 Outbreak: A Scoping Review.

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, pharmacists have been on the front lines of health care, offering vital services. Consequently, the need for pharmacists to support an effective antibiotic stewardship (AMS) program during the COVID-19 outbreak has become increasingly evident. This scoping review was performed to examine related articles in 2020-2022 published in the Scopus, SAGE, and Cochrane databases with the keywords "Pharmacist" and "Antibiotic Stewardship" and "COVID-19". The inclusion criteria were full-text articles written in English. A total of 15 articles were included in this review to describe the role of pharmacists in AMS during the COVID-19 outbreak. In general, pharmacists are responsible for identifying and treating patients during pandemics, ensuring the continued supply and accessibility of medications, promoting health policies, and monitoring antibiotic use for COVID-19 cases and co-infections. At the hospital, as the most significant element for pharmacists on the AMS team, the apparent change is demonstrated in educating patients on telehealth services, clarifying misconceptions about treatments and antibiotic consumption, as well as taking a leadership position to establish local guidelines for the COVID-19 treatment protocol. Pharmacists have an important role in the AMS program, and the COVID-19 pandemic was perceived as a highlight their importance. Therefore, their work with the AMS program needs to be improved as they learn to extend their role in telehealth services, educate and clarify the misconceptions about COVID-19 treatments and other antibiotic consumption in the community, inventory control the COVID-19 drug, antibiotics, and vaccine, as well as take the lead in establishing local guidelines on antibiotic consumption during the pandemic outbreak.

Transcriptional Biomarkers for Treatment Monitoring of Pulmonary Drug-Resistant Tuberculosis: Protocol for a Prospective Observational Study in Indonesia.

Many blood-based gene expression biomarkers for monitoring tuberculosis (TB) treatment have been suggested so far, but promising biomarker results for drug-resistant TB treatment response have not been studied. This protocol presents a prospective observational study in Indonesia to profile the human blood transcriptome for predicting the response to drug-resistant TB treatment, focusing on pulmonary TB, and to adapt the specific RNA signature to the qRT-PCR platform. Longitudinal blood samples will be collected from 44 subjects with rifampicin resistant TB, confirmed by Xpert MTB/RIF, and 52 healthy controls. RNA-Seq will be performed to identify changes in the transcriptome following TB treatment. A discriminative RNA signature will be chosen and translated into a score for use in a quantitative PCR-based assay. This study will provide crucial information to guide the discovery and design of a clinically implementable tool to monitor the response of TB treatment.

Multi Epitope-Based Vaccine Design for Protection Against Mycobacterium tuberculosis and SARS-CoV-2 Coinfection.

Background: A prophylactic and immunotherapeutic vaccine for Mycobacterium tuberculosis (MTB) and SARS-CoV-2 coinfection needs to be developed for a proactive and effective therapeutic approach. Therefore, this study aims to use immunoinformatics to design a multi-epitope vaccine for protection against MTB and SARS-CoV-2 coinfection. Methods: The bioinformatic techniques were used to screen and construct potential epitopes from outer membrane protein A Rv0899 of MTB and spike glycoprotein of SARS-CoV-2 for B and T cells. The antigenicity, allergenicity, and several physiochemical properties of the developed multi-epitope vaccination were then evaluated. Additionally, molecular docking and normal mode analysis (NMA) were utilized in evaluating the vaccine's immunogenicity and complex stability. Results: Selected proteins and predicted epitopes suggest that the vaccine prediction can be helpful in the protection against both SARS-CoV-2 and MTB coinfection. Through docking molecular and NMA, the vaccine-TLR4 protein interaction was predicted to be efficient with a high level of IgG, T-helper cells, T-cytotoxic cells, andIFN-γ. Conclusion: This epitope-based vaccine is a potentially attractive tool for SARS-CoV-2 and MTB coinfection vaccine development.

Omics Biomarkers for Monitoring Tuberculosis Treatment: A Mini-Review of Recent Insights and Future Approaches.

Poor sensitivity of sputum conversion for monitoring tuberculosis (TB) treatment that makes identification of a non-sputum-based biomarker is urgently needed. Monitoring biomarkers in TB treatment is used to decide whether critical thresholds have been reached and helps clinicians to conclude the therapeutic success. In this mini review, we highlight recent studies on omics-related contributes to identifying of a novel biomarker as surrogate markers for the cure and predicting future reactivation risk following TB treatment. We catalogue the studies published to seek the progress made in transcriptomics, proteomics, and metabolomics in pulmonary TB. We also discuss how integrative multi-omics data will provide further understanding and effective TB treatment, such as revealing the interrelationships at multiple molecular levels, facilitating the identification of biologically interconnected processes, and accelerating precision medicine in TB treatment. However, proper validation in prospective longitudinal studies with long-term follow-up and outcome assessment must be conducted before the biomarkers are utilized in clinical practice.

A Narrative Review of Statin-Induced Rhabdomyolysis: Molecular Mechanism, Risk Factors, and Management.

Although statins are effective for treating hypercholesterolemia, they can have various side effects, including rhabdomyolysis, a potentially fatal condition. This review evaluated the incidence and underlying molecular mechanism of statin-induced rhabdomyolysis and analyzed its risk factors, prevention, and management. We focused on the clinical and randomized clinical trials of statin monotherapies and combinations with other drugs. The primary mechanism of statin therapy-induced rhabdomyolysis is believed to be a decrease in ubiquinone (coenzyme Q) produced by the HMG-CoA pathway. Additionally, different types of lipophilic and hydrophilic statins play a role in causing rhabdomyolysis. Although statin-induced rhabdomyolysis has a low incidence, there is no guarantee that patients will be free of this side effect. Rhabdomyolysis can be prevented by reducing the risk factors, such as using CYP3A4 inhibitors, using high-dose statins, and strenuous physical activities.

Regulation of mitogen-activated protein kinase signaling pathway and proinflammatory cytokines by ursolic acid in murine macrophages infected with Mycobacterium avium.

Mycobacterium avium, one of the closest relatives of Mycobacterium tuberculosis (MTB), offers an advantage in studying MTB because of its tuberculosis-like effect in humans and host immune tolerance. This study examined the antimycobacterial action of ursolic acid and its regulation in macrophages during infection. Colonyforming units of the bacteria were determined in the cell lysate of macrophages and in the supernatant. The effect of ursolic acid on macrophages during infection was determined by analyzing the phosphorylation of the mitogen-activated protein kinase signaling pathway and the concentrations of tumor necrosis factor-α, interleukin-1ß, interleukin-6, and nitrite. The colony-forming units analysis demonstrated that ursolic acid reduced the presence of Mycobacterium avium both intracellularly (in macrophages) and extracellularly. It decreased the levels of tumor necrosis factor- α and interleukin-6 but increased the concentrations of interleukin-1ß and nitrite during infection. It also inhibited the phosphorylation of ERK1/2 but phosphorylated the C-Jun N-terminal kinase signaling pathway. The antimycobacterial effect of ursolic acid correlated with its ability to regulate the activation of macrophages. This dual ability made the ursolic acid-related elimination of the mycobacteria more effective.