Anti-tuberculosis Research Articles

Norwegian scabies in HIV and tuberculosis infected patient: A case report

Norwegian scabies is a rare scabies with the manifestation of thick crusts of the extremities of the skin that contain eggs and mites. Several conditions in which scabies infection is easily transmitted include immunocompromised, home nursing, and severe neurological disorder. The aim of this case report was to present a thorough analysis of a comprehensive resource for the management of Norwegian scabies patients, with a specific focus on individuals who also have HIV or other immunocompromising diseases. A 56 – year – old female presented with dermatitis lesions and itching with sever hyperkeratosis, several maculae and papules on neck and armpits for four months duration.Sarcoptes scabiei was found from microscopy examination of skin scraping. The patient received antiretroviral drugs, antituberculosis medication and scabicidal treatment.

Surface-modified dendrimer nanoconjugate for targeting delivery of rifampicin

ObjectiveThe study aimed to formulate and evaluate the efficiency of surface-modified Polyamidoamine dendrimer (PAMAM) as a targeted nanocarrier for the antimycobacterial agent rifampicin. MethodsThe periphery of dendrimer was modified with mannose using α-D-mannopyranosylphenyl isothiocyanate and characterized using analytical techniques i.e., infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR). Then, rifampicin was encapsulated into mannosylated dendrimers and evaluated for size, shape, encapsulation efficiency (EE%), drug-dendrimer interaction, and drug release. The toxicity of the nanoconjugates were assessed towards macrophages using the MTT technique. The study investigated the internalization of dendrimer nanoparticles into macrophages to assess the impact of mannose conjugation. Dendrimers were fluorescently labelled and the internalization was quantified using a fluorescence spectroscopy and flow cytometer methods. ResultsMannosylated dendrimers with different mannose densities were successfully developed. The nanoparticles were within the nanoscopic scale. The dendrimers appeared spheroidal under scanning electron microscopy (SEM), and thermal analysis confirmed the conjugation of rifampicin into the dendrimers. The nanoparticles exhibited a good EE% for rifampicin at 10.34 % w/w. After surface mannosylation, the EE% further increased, ranging from 43.43 % to 57.91 % w/w. Mannose-functionalized dendrimers prolonged rifampicin release in physiological pH, while a rapid release in pH 4.5 medium was noticed. The cytotoxicity of the dendrimers in RAW macrophages was considerably reduced after mannose functionalization. In vitro studies indicated that mannose significantly increased the macrophage uptake of nanoconjugates, likely via lectin receptor-mediated endocytosis. ConclusionOverall results suggested mannosylated dendrimers as an effective targeted pulmonary delivery system for rifampicin with negligible cytotoxicity.

Therapeutic Potential of Silver Nanoparticles (AgNPs) as an Antimycobacterial Agent: A Comprehensive Review.

The uncontrolled emergence of multidrug-resistant mycobacterial strains presents as the primary determinant of the present crisis in antimycobacterial therapeutics and underscores tuberculosis (TB) as a daunting global health concern. There is an urgent requirement for drug development for the treatment of TB. Numerous novel molecules are presently undergoing clinical investigation as part of TB drug development. However, the complex cell wall and the lifecycle of M. tuberculosis within the host pose a significant challenge to the development of new drugs and, therefore, led to a shift in research focus towards alternative antibacterial compounds, notably nanotechnology. A novel approach to TB therapy utilizing silver nanoparticles (AgNPs) holds the potential to address the medical limitations imposed by drug resistance commonly associated with currently available antibiotics. Their broad-spectrum antimicrobial activity presents the utilization of AgNPs as a promising avenue for the development of therapeutics targeting mycobacterial-induced diseases, which can effectively target Mycobacterium tuberculosis, including drug-resistant strains. AgNPs can enhance the effectiveness of traditional antibiotics, potentially leading to better treatment outcomes and a shorter duration of therapy. However, the successful implementation of this complementary strategy is contingent upon addressing several pivotal therapeutic challenges, including suboptimal delivery, variability in intra-macrophagic antimycobacterial effect, and potential toxicity. Future perspectives may involve developing targeted delivery systems that maximize therapeutic effects and minimize side effects, as well as exploring combinations with existing TB medications to enhance treatment outcomes. We have attempted to provide a comprehensive overview of the antimycobacterial activity of AgNPs, and critically analyze the advantages and limitations of employing silver nanoparticles in the treatment of TB.

Disseminated Bacille Calmette-Guérin Vaccine-Induced Disease in a Sample of Iranian Children: A Longitudinal Case-Series Study

Background: Approximately a quarter-million Iranian newborns receive the Bacille Calmette-Guérin (BCG) vaccine annually. However, in immunodeficient infants, this vaccine can lead to disseminated BCG disease (DBD). Objectives: This study aims to determine the clinical presentation, comorbidities, underlying immunodeficiency, and prognosis of DBD in a group of Iranian children. Methods: In a longitudinal case-series study, data were collected from the files of infants and children diagnosed with DBD from 2005 to 2017. Immunodeficiency screening was conducted for each patient. For children with normal immunodeficiency screening results, further testing for Mendelian susceptibility to mycobacterial diseases (MSMD) was performed. Detection of DBD in children was achieved by evaluating gastric lavage and bone marrow aspiration samples for mycobacterium. Results: Most of the 22 patients were immunocompromised, with the following distribution: 31.8% had severe combined immunodeficiency (SCID), 45.5% had MSMD (specifically IL-12Rβ1 deficiency), one patient (4.5%) had Wiskott-Aldrich syndrome (WAS), and the remaining 18.1% had unknown immunodeficiency types. Most patients with MSMD were successfully treated and did not show relapse during the follow-up period, even after discontinuing anti-tuberculosis (TB) medications. Conclusions: Due to the similarity of its manifestations to sepsis, diagnosing systemic infections caused by the BCG vaccine in children requires a high level of clinical suspicion and appropriate diagnostic measures, such as mycobacterial culture, biochemical speciation, or polymerase chain reaction (PCR). These diagnostic steps should be taken promptly in cases of DBD, with concurrent treatment using anti-tuberculosis drugs and, if possible, targeted therapies for underlying immunodeficiency.

JIB-04, an inhibitor of Jumonji histone demethylase as a potent antitubercular agent against Mycobacterium tuberculosis.

The increasing drug resistance of Mycobacterium tuberculosis (Mtb), coupled with the limited availability of effective anti-tuberculosis medications, poses significant challenges for the management and treatment of tuberculosis (TB). Globally, non-tuberculous mycobacteria (NTM) infections are increasing, with Mycobacterium avium complex and Mycobacterium abscessus (Mab) being the most common in labs and having few treatment options. There's an urgent need for innovative therapies against Mtb and NTM that are effective and have minimal side effects. The study evaluated the in vitro efficacy of JIB-04, a Jumonji histone demethylase inhibitor, against Mtb, Mab, and multidrug-resistant (MDR) clinical isolates using the minimum inhibitory concentration (MIC) assay. We also determined the minimum bactericidal concentrations (MBCs) of JIB-04 against the H37Rv and H37Ra strains. A time-kill assay was performed to assess the comparative efficacy of JIB-04 and rifampicin against H37Ra. Additionally, the study investigated the impact of JIB-04 on biofilm formation and the persistence of H37Ra over extended periods. Our findings demonstrated a substantial inhibitory effect of JIB-04 on the growth of Mab, Mtb, and MDR clinical isolates. JIB-04 showed bactericidal effects at twice the MIC, outperforming rifampicin in reducing viable cell counts over 8 days. It showed moderate cytotoxicity to mammalian cells but effectively inhibited biofilm formation. In our anoxia model, JIB-04 induced a significant, concentration-dependent reduction in bacterial load. JIB-04 is a promising candidate for the treatment of MDR tuberculosis.

Exploring the Chemical Space of Mycobacterial Oxidative Phosphorylation Inhibitors Using Molecular Modeling.

Mycobacteria are opportunistic intracellular pathogens that have plagued humans and other animals throughout history and still are today. They manipulate and hijack phagocytic cells of immune systems, enabling them to occupy this peculiar infection niche. Mycobacteria exploit a plethora of mechanisms to resist antimicrobials (e. g., waxy cell walls, efflux pumps, target modification, biofilms, etc.) thereby evolving into superbugs, such as extensively drug-resistant tuberculosis (XDR TB) bacilli and the emerging pathogenic Mycobacterium abscessus complex. This review summarizes the mechanisms of action of some of the surging antimycobacterial strategies. Exploiting the fact that mycobacteria are obligate aerobes and the differences between their oxidative phosphorylation pathways versus their human counterpart opens a promising avenue for drug discovery. The polymorphism of respiratory complexes across mycobacterial pathogens imposes challenges on the repositioning of antimycobacterial agents to battle the rise in nontuberculous mycobacterial infections. In silico strategies exploiting mycobacterial respiratory machinery data to design novel therapeutic agents are touched upon. The potential druggability of mycobacterial respiratory elements is reviewed. Future research addressing the health challenges associated with mycobacterial pathogens is discussed.

Time to Cure and Predictive Factors Among Patients with Multi-Drug Resistance Tuberculosis in Puntland, Somalia: A Retrospective Cohort Study

Background: Multi-drug-resistant tuberculosis, also known as MDR-TB, is caused by bacteria that are resistant to the most effective first-line anti-tuberculosis medications, which are rifampicin and isoniazid. MDR-TB is an increasing global concern, and its spread has varying cure times for patients affected. Thus, this study was intended to investigate the median time to cure and identify predictive factors for patients with MDR-TB in Puntland, Somalia. Methods: A retrospective cohort study was carried out at the MDR-TB center in Galkayo, Puntland, Somalia between the years of July 2017 and August 2023. The study utilized data that were collected from the inquiry form and monitoring cards of a randomly selected sample of 130 patients over a 6-year period. The data were entered into Epi-Data version 4.3 and analyzed using R Programming version 4.4.0. Non-parametric methods were used to estimate the median time to cure for patients with MDR-TB. Semi-parametric and parametric models were employed to determine predictive factors that influence the time to cure for MDR-TB patients. The Akaike Information Criteria (AIC) and Bayesian Information Criteria (BIC) of different survival models were compared to select the model that offers the best fit. Results: Out of the total of MDR-TB patients, 109(83.85%) were cured and 21(16.15%) were censored during the follow-up period. The median time to cure from MDR-TB was found to be 619 days which is approximately 20 months. In accordance with the AIC and BIC, the Log-logistic accelerated failure time model was the best fit for the data as compared to the other AFT models. The result of the Log-logistic AFT model revealed that age, sex, disease site, and comorbidities significantly affect the time to cure for MDR-TB. According to this study, older age with MDR-TB patients, male MDR-TB patients, MDR-TB patients with comorbid conditions, and extrapulmonary MDR-TB patients had a longer time to cure than their reference categories. Conclusion: Based on the findings of the study, the median time to cure for patients with MDR-TB in Puntland was found to be 20 months. Sex, disease site, comorbidities and age were predictive factors of time to cure from MDR-TB.

A conservative management approach for spinal tuberculosis causing cauda equine syndrome in pregnancy

Background: Spinal tuberculosis in pregnancy leading to neurological sequelae is rare and a challenging condition to manage. The usual approach is to perform urgent decompression surgery, but patients with a more stable course of the disease may benefit from a conservative approach with anti-tuberculosis (ATT) therapy.Case presentation: A pregnant mother in her second trimester presented with a history of chronic backache exacerbated by right-sided foot drop, L5 root sensory loss and intermittent urinary retention. MRI revealed L5 vertebral collapse with para-vertebral collection causing cauda equine compression at the L5-S1 level. High ESR, strongly positive tuberculin test, and the clinical and radiological findings were compatible with a diagnosis of spinal tuberculosis. Based on the multi-disciplinary team’s decision, a conservative management approach with ATT and supportive therapy was initiated with close observation. The patient showed a remarkable response to ATT with clinical and radiological improvement. She underwent an elective caesarean section at 37 weeks and delivered a healthy baby. On the fourth week postpartum, she underwent decompressive surgery with complete neurological recovery,Discussion and conclusion: Spinal TB in pregnancy causing neurological impairment is usually managed with urgent surgical interventions. This is one of the few reported cases where a conservative approach was undertaken, with close observation and a positive outcome.Therefore, it is important to carefully select patients needing surgical interventions and those who would benefit better from a conservative approach. High suspicion, early diagnosis, prompt treatment initiation and close monitoring are vital components in achieving the best outcome.

Pattern of Adverse Drug Reactions and Performed Monitoring Laboratory-Tests in Patients Receiving Anti Tuberculosis Treatment in an Endemic Region, Zabol

Background: Efficient anti TB treatment considered crucial globally. Anti TB drugs can cause various adverse drug reactions (ADRs). Clinical and laboratory monitoring will decrease rate of these ADRs, improve patient safety as well as drug adherence and treatment outcome. Methods: In this cross-sectional study total of 136 newly diagnosed TB patients were included. All patients received standard anti-TB 4 drug regimen. Predesigned data collection forms were used to gather patient’s lab data as well as clinical symptoms they experienced during treatment course. Monthly follow up visits or phone calls were also performed by investigators and all health issues were recorded. Results: The majority of our patients aged over 70-year-old. About 54% of them were female. We recorded at least one ADR in 80.8% of patients, and hepatic-gastrointestinal (GI) ADRs ranked first (64.7%). Although ADRs were more common in women and patients over 70-year-old, but there was no statistically significant relationship between sex or age and rate of ADRs (P> 0.05). We also observed that recommended baseline laboratory tests for monitoring anti TB treatment was not performed in any of our patients, except complete blood count (CBC) that was performed in 11 cases. This led to diagnoses of anemia and thrombocytopenia in one case. Conclusion: The majority of our patients experienced ADR. Recommended drug monitoring tests that could guarantee safe and effective treatment were not performed routinely in our TB management centres. These facts highlighted the importance of improving surveillance system for TB management based on national standards.

Exploring Benzo[h]chromene Derivatives as Agents against Protozoal and Mycobacterial Infections

Background/Objectives: In this study, the efficacy of benzo[h]chromene derivatives as antiprotozoal and antimycobacterial agents was explored. Methods: A total of twenty compounds, including benzo[h]chromene alkyl diesters and benzo[h]chromene-triazole derivatives, were synthesized and tested against Trypanosoma cruzi, Leishmania braziliensis, L. infantum, and strains of Mycobacterium abscessus and Mycobacterium intracellulare LIID-01. Notably, compounds 1a, 1b, 2a, and 3f exhibited superior activity against Trypanosoma cruzi, with IC50 values of 19.2, 37.3, 68.7, and 24.7 µM, respectively, outperforming the reference drug benznidazole (IC50: 54.7 µM). Results: Compounds 1b and 3f showed excellent selectivity indices against Leishmania braziliensis, with SI values of 19 and 18, respectively, suggesting they could be potential alternatives to the commonly used, but more selective, miltefosine (IC50: 64.0 µM, SI: 43.0). Additionally, compounds 1a, 1b, and 3f were most effective against Leishmania infantum, with IC50 values of 24.9, 30.5, and 46.6 µM, respectively. Compounds 3f and 3h were particularly potent against various Mycobacterium abscessus strains, highlighting their significance given the inherent resistance of these bacteria to standard antimicrobials. Conclusions: The sensitivity of Mycobacterium intracellulare LIID-01 to these compounds also underscored their potential in managing infections by the Mycobacterium avium–intracellulare complex.

Allosteric coupling of substrate binding and proton translocation in MmpL3 transporter from Mycobacterium tuberculosis.

Infections caused by Mycobacterium spp. are very challenging to treat, and multidrug-resistant strains rapidly spread in human populations. Major contributing factors include the unique physiological features of these bacteria, drug efflux, and the low permeability barrier of their outer membrane. Here, we focus on MmpL3 from Mycobacterium tuberculosis, an essential inner membrane transporter of the resistance-nodulation-division superfamily required for the translocation of mycolic acids in the form of trehalose monomycolates (TMM) from the cytoplasm or plasma membrane to the periplasm or outer membrane. The MmpL3-dependent transport of TMM is essential for the growth of M. tuberculosis in vitro, inside macrophages, and in M. tuberculosis-infected mice. MmpL3 is also a validated target for several recently identified anti-mycobacterial agents. In this study, we reconstituted the lipid transport activity of the purified MmpL3 using a two-lipid vesicle system and established the ability of MmpL3 to actively extract phospholipids from the outer leaflet of a lipid bilayer. In contrast, we found that MmpL3 lacks the ability to translocate the same phospholipid substrate across the plasma membrane indicating that it is not an energy-dependent flippase. The lipid extraction activity was modulated by substitutions in critical charged and polar residues of the periplasmic substrate-binding pocket of MmpL3, coupled to the proton transfer activity of MmpL3 and inhibited by a small molecule inhibitor SQ109. Based on the results, we propose a mechanism of allosteric coupling wherein substrate translocation by MmpL3 is coupled to the energy provided by the downhill transfer of protons. The reconstituted activities will facilitate understanding the mechanism of MmpL3-dependent transport of lipids and the discovery of new therapeutic options for Mycobacterium spp. infections.IMPORTANCEMmpL3 from Mycobacterium tuberculosis is an essential transporter involved in the assembly of the mycobacterial outer membrane. It is also an important target in undergoing efforts to discover new anti-tuberculosis drugs effective against multidrug-resistant strains spreading in human populations. The recent breakthrough structural studies uncovered features of MmpL3 that suggested a possible lipid transport mechanism. In this study, we reconstituted and characterized the lipid transport activity of MmpL3 and demonstrated that this activity is blocked by MmpL3 inhibitors and substrate mimics. We further uncovered the mechanism of how the binding of a substrate in the periplasmic domain is communicated to the transmembrane proton relay of MmpL3. The uncovered mechanism and the developed assays provide new opportunities for mechanistic analyses of MmpL3 function and its inhibition.

Exploration of vanoxerine analogues as antibacterial agents.

Mycobacterium tuberculosis is a bacterial pathogen, responsible for approximately 1.3 million deaths in 2022 through tuberculosis infections. The complex treatment regimen required to treat tuberculosis and growing rates of drug resistance, necessitates the development of new anti-mycobacterial agents. One approach is to repurpose drugs from other clinical applications. Vanoxerine (GBR 12909) was previously shown to have anti-mycobacterial activity, through dissipating the membrane electric potential and hence, cellular energetics. Several vanoxerine analogues were synthesised in this study, which exhibited a range of activities against mycobacteria and enterococcus. All active analogues had similar impacts on the membrane electric potential and inhibition of ethidium bromide efflux. The most active compound displayed reduced inhibitory activity against the known human target of vanoxerine, the dopamine transporter. This work has identified a promising analogue, which could provide a starting point for further medicinal chemistry and drug development efforts to target mycobacteria.

Nationwide usage of ethambutol and incidence and screening practices of optic neuropathy.

Ethambutol, a key anti-tuberculosis medication, is associated with optic neuropathy, which can lead to significant vision impairment. This population-based cohort study investigated the nationwide usage of ethambutol and the incidence and screening of optic neuropathy among ethambutol users. The cohort included 206,157 individuals from the Health Insurance Review and Assessment database in South Korea who initiated ethambutol therapy between 1 January 2015, and 31 December 2021. Among them, 117,309 individuals without prior ophthalmic diseases were analyzed to investigate practice patterns. The timing of the baseline examinations (an ophthalmic examination immediately preceding [within 1month] ethambutol initiation or the first ophthalmic assessment conducted after the initiation) and subsequent monitoring and modalities used were assessed. The cumulative incidences of the optic neuropathy categories, overall optic neuropathy, optic neuropathy/optic neuritis, and optic atrophy, were analyzed. The annual number of ethambutol users declined over time between 2015 and 2021. The cumulative incidences of overall optic neuropathy, optic neuropathy/optic neuritis, and optic atrophy were 2.8%, 2.0%, and 0.7%, respectively. Optical coherence tomography usage for ophthalmic examinations remarkably increased from 23.9% in 2015 to 85.5% in 2021, while visual field examinations were frequently (69.6%) employed for functional assessment at the time of diagnosis. Baseline screening within 6months of initiating ethambutol therapy was performed in 12.0%-13.1% of ethambutol initiators annually over the study period. The percentage of ethambutol initiators receiving subsequent monitoring within 6months following baseline screening declined over time, from 13.1% in 2015 to 7.9% in 2021. The diminishing trend in monitoring emphasizes the need for improved pharmacovigilance to reduce the risk of optic atrophy and blindness through early detection.

EVALUASI PENGGUNAAN OBAT ANTITUBERKULOSIS PARU DIPUSKESMAS: NARRATIVE LITERATURE REVIEW

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. While it primarily affects the lungs, it can also impact other organs. In Indonesia, pulmonary TB remains a significant health issue. This study aims to evaluate the use of anti-tuberculosis medications at various community health centers (puskesmas) in Indonesia through a literature review. The research method employed involves a literature review with searches conducted on Google Scholar and PubMed databases. Out of 360 articles found on Google Scholar and 13,026 articles on PubMed, 8 relevant articles were identified for this study. The results indicate that the most commonly used treatment regimen is Category 1, which includes a 2-month intensive phase with a combination of Isoniazid 75 mg, Rifampicin 150 mg, Pyrazinamide 400 mg, and Ethambutol 275 mg, followed by a 4-month continuation phase with Rifampicin 150 mg and Isoniazid 150 mg. This medication regimen aligns with the Tuberculosis Control Guidelines issued by the Indonesian Ministry of Health in 2016. The evaluation shows that Indonesian puskesmas generally adhere to the established treatment guidelines but still require further monitoring to ensure adherence and effectiveness of the treatment.

Cervical Lymphadenitis Tuberculosis Coexistent with Metastatic Papillary Thyroid Carcinoma.

Malignant lesions and tuberculosis coexisting at the same anatomical site in a patient are extremely uncommon. We present a case of a 53-year-old female with cervical lymphadenitis tuberculosis combined with metastatic papillary thyroid carcinoma. Thyroidectomy was performed on the patient with central and lateral neck dissection. The patient received anti-tuberculosis medication and radioactive iodine ablation. No recurrence was observed during a 2-year follow-up period.

Natural and Bioinspired Lipidic Alkynylcarbinols as Leishmanicidal, Antiplasmodial, Trypanocidal, Fungicidal, Antibacterial, and Antimycobacterial Agents.

The present review article recapitulates for the first time the antipathogenic biological data of a series of lipidic natural products and synthetic analogues thereof characterized by the presence in their structure of an alkynylcarbinol unit. The cytotoxic properties of such natural and bioinspired compounds have been covered by several literature overviews, but to date, no review article detailing their activity against pathogens has been proposed. This article thus aims at providing a comprehensive overview of the field including early studies from the 1970s and 1980s with a specific focus on results published from the late 1990s until nowadays. Publications presenting the data of almost 50 different natural products are reported. Detailed activities encompass the fields of leishmanicidal, antiplasmodial, trypanocidal, fungicidal, and mainly antibacterial and antimycobacterial compounds. The few published studies aimed at exploring the structure-activity relationship in these series are also described. Around 15 different synthetic analogues of natural products, selected among the most active reported, are also presented. The rare data available regarding the antipathogenic mode of action of these products are recalled, and finally, a comparative analysis of the available biological data is proposed with the aim of identifying the key structural determinants for the bioactivity against pathogens of these unusual compounds.

A network pharmacology-based approach to understand the mechanism of action of anti-mycobacterial activity of Acacia nilotica: a modelling and experimental study.

The rapid rise in drug-resistant tuberculosis poses a serious threat to public health and demands the discovery of new anti-mycobacterial agents. Medicinal plants are a proven potential source of bioactive compounds; however, identifying those responsible for the putative anti-mycobacterial action still remains a challenging task. In this study, we undertook a systematic network pharmacology approach to identify and evaluate anti-mycobacterial compounds from a traditional plant, Acacia nilotica, as a model system. The protein-protein interaction network revealed 17 key pathways in M. tuberculosis encompassing 40 unique druggable targets that are necessary for its growth and survival. The phytochemicals of A. nilotica were preferentially found to interfere with the cell division and cell wall biogenesis proteins, especially FtsZ and Mur. Notably, the compounds epigallocatechin, ellagic acid, chlorogenic acid, and D-pinitol were found to exhibit a potential polypharmacological effect against multiple proteins. Further, in vitro studies confirmed that the selected candidates, chlorogenic acid, and ellagic acid exhibited potent anti-mycobacterial activity (against M. smegmatis) with specific inhibition of purified M.tb FtsZ enzyme. Taken together, the present study demonstrates that network pharmacology combined with molecular docking can be utilized as an efficient approach to identify potential bioactive phytochemicals from natural products along with their mechanism of action. Hence, the compounds identified in this study can be potential lead candidates for developing novel anti-mycobacterial drugs, while the key proteins identified here can be potential drug targets.

The Relationship Between Compliance in Taking Anti Tuberculosis Drugs and the Results of Acid-Fast Bacteria (AFB) Examination as an Indicator of Recovery of TB Patients in Tanjung Pinang City in 2022-2023

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis with a treatment period of 6 to 8 months. Mycobacterium tuberculosis can become germ resistant or multidrug resistance (MDR) if you do not comply in taking anti-tuberculosis drugs (ATD), making this disease very difficult to cure. This research uses secondary data from the Tanjung Pinang City Population Control and Family Planning Health Service for 2022-2023. The aim is to determine the relationship between compliance in taking Anti-Tuberculosis Drugs (ATD) and the results of acid-fast bacteria (AFB) examinations of TB patients in Tanjung Pinang City. The research methodology was observational analytic using a cross-sectional design, with a total sampling technique from pulmonary TB patients with positive AFB, negative AFB with positive thorax and extrapulmonary, 252 TB patients. Data analysis used the Fisher Exact test with a confidence level of 95%. The results of data analysis showed that 91.3% of patients complied in taking drugs, and 87.3% recovered with negative AFB results. Fisher Exact analysis showed a significant difference in proportion between compliance in taking anti-tuberculosis drugs and the results of AFB examination of pulmonary TB patients with a p-value of 0.000 (p < ∝0.05). The conclusion from this study is that there is a relationship between compliance in taking anti-tuberculosis drugs and the results of AFB examinations of pulmonary TB patients in Tanjung Pinang City in 2022-2023. Keywords: Pulmonary TB, ATD, (AFB), Ziehl Neelsen

Repurposing antiparasitic N,N'-aliphatic diamine derivatives as promising antimycobacterial agents.

In previous studies, we demonstrated the potent activity of a library of 25 N,N'-disubstituted diamines (NNDDA) toward Trypanosomatid and Apicomplexa parasites. Considering the structure similarity between this collection and SQ109, an antituberculosis compound, and its compelling antiparasitic properties, we aimed to repurpose this library for tuberculosis treatment. We assayed this collection against Mycobacterium tuberculosis H37Rv and M. avium, obtaining several compounds with MIC values below 10 µM. The most active analogs were also evaluated against M. smegmatis, a non-pathogenic species, and the non-tuberculosis mycobacteria M. abscessus, M. kansasii, and M. fortuitum. 3c stands out as the lead mycobacterial compound of the collection, with potent activity against M. tuberculosis (minimal inhibitory concentration [MIC] = 3.4 µM) and moderate activity against M. smegmatis, M. kansasii, and M. fortuitum (all with MIC values of 26.8 µM). To unravel the mechanism of action, we employed the web-based platform Polypharmacology Browser 2 (PPB2), obtaining carbonic anhydrases as potential drug targets. Nevertheless, none of the compounds displayed experimental inhibition. In summary, our study confirms the validity of the repurposing approach and underscores the antimycobacterial potential of NNDDA compounds, especially the analog 3c, setting a stepping stone for further studies.

Discovery of potent anti–tuberculosis agents targeting aminoacyl–tRNA synthetases

Discovery of potent anti–tuberculosis agents targeting aminoacyl–tRNA synthetases