Anti-tuberculosis Research Articles

Female genital tuberculosis presenting as a protruding anterior vaginal wall mass: a case report

Although pulmonary tuberculosis is a common infectious disease, especially in low-and middle-income countries, female genital tract tuberculosis (TB) is rarely reported. Female genital TB might be asymptomatic or manifest clinically in an unusual way, making an early diagnosis challenging. The most often affected regions of the genital system are the fallopian tubes and endometrium. Menstrual abnormalities, infertility, and chronic pelvic pain are frequent presenting symptoms. Rare reports of vulvar and vaginal TB exist. This case report features a 35-year-old woman who had a bulging tumor in her vagina for a year before being identified with anterior vaginal wall TB, treated with anti-tuberculosis medication, and made improvements.

P0296 Comparison of clinical characteristics of Montreal classification group A3 patients with Crohn’s disease in Korea: Results from the Prospective and Retrospective CONNECT Study

Abstract Background The CONNECT study, a nationwide multicenter cohort study of Crohn’s disease (CD) in Korea, was designed to investigate the clinical characteristics and long-term prognosis of CD patients. Starting in 2009, the study enrolled patients in both a prospective cohort (patients diagnosed since 2009) and a retrospective cohort (patients diagnosed before 2009). Recent trends show an increase in elderly-onset CD (EOCD) in Korea, alongside cases in younger individuals; however, research focusing specifically on EOCD patients remains limited. This study aims to evaluate the clinical characteristics and long-term outcomes of EOCD patients using data from this nationwide, multicenter cohort in Korea. Methods We analyzed data both the prospective and retrospective CONNECT cohorts, which included 2,399 CD patients diagnosed between 1982 and 2019 (retrospective cohort of 1,224 patients, prospective cohort of 1,175 patients). Of these, 244 patients were identified as having Montreal classification A3 at diagnosis. Fifty-six EOCD patients (diagnosed at age 60 or older) were compared with 188 adult-onset CD patients (diagnosed at age 40-59) in aspects of baseline characteristics, medication use, and bowel resection rates. Results EOCD patients had a higher proportion of females (55.4%) compared to the adult-onset CD group (31.5%). Ileal involvement was the most common location of disease at diagnosis in EOCD patients (51.8%). Previous use of anti-tuberculosis medication was more frequent in EOCD patients than in the adult-onset CD group (29.6% vs. 16.3%, p = 0.047). Although there were no significant differences in disease behavior at diagnosis or ever use of medication between the groups, EOCD patients showed a significantly lower risk of bowel resection (p = 0.008). Conclusion EOCD patients in Korea appear to present with distinct clinical features and have a more favorable prognosis, as evidenced by a reduced need for bowel resection compared with adult-onset CD patients. Further research is essential to better understand the unique needs of EOCD patients, including the development of tailored therapeutic guidelines that address the complexities associated with aging and the management of CD.

Systematic Determination of the Impact of Structural Edits on Accumulation into Mycobacteria.

The mycomembrane of mycobacteria has long been regarded as the primary barrier to the accumulation of molecules within these bacteria. Understanding accumulation beyond the mycomembrane of Mycobacterium tuberculosis ( Mtb ) is crucial for developing effective antimycobacterial agents. This study investigates two design principles commonly found in natural products and mammalian cell-permeable peptides - backbone N -methylation and macrocyclization - aimed at enhancing accumulation. To assess the impact of these structural edits on accumulation, we employed our recently described Peptidoglycan Accessibility Click-Mediated Assessment (PAC-MAN) assay for live-cell analysis. Our findings indicate that peptide macrocyclization generally enhances permeability and metabolic stability, while N -methylation modifies accumulation in a context-dependent manner. Furthermore, we applied these design principles to the peptide antibiotic Tridecaptin A1, demonstrating improved permeability and efficacy against mycobacteria, in specific contexts. This work suggests that strategic structural modifications can enhance accumulation past the mycomembrane and provide the first systematic governing rules for the rational redesign of potential antimycobacterial agents. Most importantly, our results broadly challenge the notion that large hydrophilic molecules ( e.g ., peptides) cannot readily bypass the mycomembrane to reach the cytosolic space.

A Cross-Sectional, Descriptive Qualitative Study of Information Counselling During Tuberculosis Treatment in South Africa: Awareness of XDR-TB Patients on Ototoxic Effects.

Ototoxicity is a significant adverse effect associated with second-line anti-tuberculosis (TB) medications, particularly in treating extensively drug-resistant TB (XDR-TB). This study investigated the awareness of ototoxic effects among adults with XDR-TB undergoing treatment in South Africa, specifically exploring the role of information counselling on ototoxic symptoms, the timing of counselling, the content covered, and the management pathways available. This cross-sectional, descriptive qualitative study was conducted at Brooklyn Chest Hospital in the Western Cape. Ten adults with XDR-TB were purposively sampled and participated in semi-structured in-depth interviews. Data were thematically analyzed and the results revealed variability in information counselling on ototoxicity, with only 30% of participants receiving comprehensive counselling that specifically addressed ototoxic symptoms. The timing of counselling was inconsistent: while 70% of participants received some information before treatment, the remainder received counselling only after treatment initiation, which may have impacted early symptom recognition. Participants' awareness of ototoxic symptoms was generally limited, with most identifying hearing loss but few recognizing other symptoms such as tinnitus or dizziness. Furthermore, only 20% of participants were provided with clear referral pathways for symptom management. These findings highlight a gap in the depth, timing, and specificity of information counselling on ototoxic effects for XDR-TB in this context. Several interventions can be implemented to address this gap.

Enhancing the antimycobacterial efficacy of pyridine-4-carbohydrazide: linkage to additional antimicrobial agents via oxocarboxylic acids.

This study evaluates the antimycobacterial potential of novel "mutual" bioactive amides, combining pyridine-4-carbohydrazide (isoniazid, INH) with various antimicrobial agents (sulphonamides, 4-aminosalicylic acid, thiosemicarbazide, diphenyl (thio)ethers) via oxocarboxylic acids. The aim was to enhance activity against both drug-susceptible and multidrug-resistant (MDR) Mycobacterium tuberculosis and non-tuberculous strains, while overcoming drug resistance through dual-action mechanisms. Many derivatives exhibited potent antimycobacterial activity, with minimum inhibitory concentrations (MICs) as low as ≤0.25 μM, outperforming INH, especially diphenyl (thio)ethers and biphenyl analogues. Additionally, the compounds were effective against M. kansasii (MICs ≤1 μM) and inhibited MDR strains at higher concentrations (≥8 μM). The cytotoxicity assay indicated a favourable safety profile, with no significant haemolysis at 125 μM, and some compounds were even protective. Selectivity for mycobacteria was confirmed by low inhibition of Gram-positive bacteria and inactivity against Gram-negative bacteria or fungi, highlighting the potential for further development as antimycobacterial agents.

Thiazole - A promising scaffold for antituberculosis agents and structure-activity relationships studies.

Research on thiazole derivatives has been a popular topic in medicine and one of the most active fields in heterocyclic chemistry. Pharmacological and industrial researchers have been studying thiazole-containing derivatives in great detail because they have a lot of biological uses. These compounds are one of the best examples of a five-membered heterocyclic compound that has a lot of potential and has had a lot of success in recent decades. Investigating viable hybrid designs utilizing thiazole is critical for the development of new anti-tuberculosis medications. This article offers a thorough overview of the latest advancements in thiazole-containing hybrids, offering potential therapeutic applications as anti-TB drugs. We also discussed the structure-activity correlations (SAR) of the powerful thiazole moiety and its several functional groups, along with a few potential molecular targets.

Synthesis of Hydrazides Derivatives as Anti-Mycobacterial Agents Mediated by the Environmental-Friendly Organocatalyst

Background: Hydrazide derivatives were synthesized using an organocatalyst, offering an environmentally friendly approach characterized by shorter reaction times, mild conditions, and the use of green solvents. Objective: The objective was to evaluate the synthesized compounds for their anti-tubercular ac-tivity against Mycobacterium tuberculosis (Mtb) and to assess the cytotoxicity of active com-pounds using the MTT assay. Methods: Ultrasound energy was employed to facilitate the synthesis of the compounds. The re-sulting compounds were tested for their activity against Mycobacterium tuberculosis (Mtb), and the active compounds were further evaluated for cytotoxicity using the 3-(4,5-dimethylthiazol-2-yl) -2,5- diphenyl tetrazolium bromide MTT assay. Results: Several compounds demonstrated activity against Mtb, with some derivatives exhibiting a Minimum Inhibitory Concentration (MIC) of 1.56 μg/mL, comparable to the standard anti-tu-bercular drug Ethambutol. Conclusion: The eco-friendly synthesis of hydrazide derivatives shows significant potential in the development of anti-tubercular agents, with some compounds displaying efficacy similar to estab-lished drugs.

Synthesis, molecular dynamics simulation and antimicrobial activity of novel s-triazine clubbed with three different hybrid pharmacophores.

To address microbial infections and combat drug resistance, we designed, synthesized, and evaluated three novel s-triazine clubbed pharmacophores: 1-acetylpyrazoline (5a-e), 2-aminopyrimidine (6a-e), and 1,5-benzodiazepine (7a-e). These were derived from chalcone (4a-e), showing improved pharmacological profiles. The compounds underwent characterization by FTIR, NMR, and Mass Spectroscopy, and their antimicrobial activities, along with structure-activity relationships (SAR), were assessed using in silico and in vitro methods. Among the tested compounds, 5c, 5e, 6d, 7a, 7d, and 7e demonstrated significant antibacterial activities with MIC values between 50 and 62.5μg/mL against Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, and Pseudomonas aeruginosa, which indicates their therapeutic potential. Similarly, 5b, 6a, 6c, 7b, and 7c exhibited vigorous antifungal activities against Candida albicans, Aspergillus niger, and Aspergillus clavatus, indicating their broad-spectrum antifungal efficacy. Moreover, the antitubercular potential of the compounds was evaluated against the Mycobacterium tuberculosis H37Rv strain, identifying 5c, 6a, 6d, 7a, and 7d as promising antimycobacterial agents. Molecular docking and molecular dynamics simulation analyses indicated excellent binding energies and stable complexes for 6c, 6e, 7a, and 7e against selected proteins from E. coli, Mycobacterium tuberculosis, and Candida albicans after 40 ns MD simulation. Compound 7a shows the best antimycobacterial activity, while 6c possessed significant antifungal properties in both in silico and in vitro analyses. Moreover, 7a and 7e exhibited desirable antibacterial activities in both experiment, indicating the synthesized compounds' broad-spectrum efficacy against various bacterial and fungal species.

Retraction notice to “Potential energy surface, effect of solvents in molecular level, experimental spectra (FTIR, Raman, UV-Visible & NMR), electronic, and dynamics simulation of isobavachalcone – Anti tuberculosis agent” [J. Mol. Liquids 392(Part 1) (2023) 123465]

Retraction notice to “Potential energy surface, effect of solvents in molecular level, experimental spectra (FTIR, Raman, UV-Visible & NMR), electronic, and dynamics simulation of isobavachalcone – Anti tuberculosis agent” [J. Mol. Liquids 392(Part 1) (2023) 123465]

Antitubercular activity of silver(I) complexes with 7-chloro-4-aminoquinolines: synthesis, characterization and in vitro biological assays

This article describes the synthesis, characterization, and biological activity of four quinoline derivatives, ACQ12, ACQ13, ACQ14, ACQophen, and their respective silver(I) complexes. The organic compounds are composed of 4,7-dichloroquinoline derivatives containing aliphatic diamines, 1,2-ethanediamine (ACQ12), 1,3-propanediamine (ACQ13), 1,4-butanediamine (ACQ14), and an aromatic diamine, o-phenylenediamine (ACQophen), as a side chain at the 4-position of the quinoline ring. The crystalline structure of ACQophen was solved by single crystal X-ray diffraction, while the crystal structures of Ag-ACQ12 (1), Ag-ACQ13 (2), Ag-ACQ14 (3), and Ag-ACQophen (4) were obtained by polycrystals X-ray diffraction technique. Silver complexes have shown a 1:1 (M:L) molar ratio. Further characterization in all compounds was performed by analytical methods and spectroscopic techniques. Elemental analyses, conductometry and IR, Raman and UV–Vis spectroscopies confirmed the proposed molecular formulas. Coordination occurs through the nitrogen atom of the quinoline ring. Biological assays in vitro were performed for all synthesized compounds against Mycobacterium tuberculosis H37Rv American Type Collection Culture 27294 (ATCC 27294). Free aminoquinolines and 3 and 4 showed MIC90 below 13.0 mg L−1. The ACQophen showed selectivity index (SI) over 190 and its Ag(I) complex has SI = 3.09, making these compounds promising antimycobacterial agents.

Retrospective study of side effects of anti-tuberculosis medications and modeling of the cumulative effect of risk factors

Background and objectives. Tuberculosis (TB) remains a significant global public health challenge. Treatment for TB typically involves a multi-drug regimen. While first-line anti-TB medications are generally effective, their associated side effects (SE) can lead to considerable morbidity and hinder treatment adherence. This study aimed to evaluate the side effects of first-line anti-TB drugs in individuals aged 18 to 55 years attending the pneumo-phthisiology department in the Gharb Region of Morocco. Materials and methods. This retrospective study was conducted in Kenitra Province, Morocco. Data were collected from 189 participants using a simple random sampling method. Two binary logistic regression models were developed: the first examined the effect of sociodemographic factors on the occurrence of side effects, and the second investigated their effect on treatment discontinuation or modification. Results. Among the patients, 37% experienced side effects, primarily cutaneous (39%), gastrointestinal (23%), and neurological (10%). Treatment discontinuation or modification occurred in 21.7% of cases. Logistic regression analysis revealed that university education and specific age groups (26–36, 37–55) were protective against treatment discontinuation (aOR = 0.084, 0.23, 0.14, respectively). Conversely, low socioeconomic status and female gender were associated with increased risk (aOR = 3.74, 6.11, respectively). Conclusions. This study underscores the importance of managing side effects of anti-TB medications by identifying key risk factors. Implementing targeted strategies can improve treatment adherence and reduce TB-related morbidity.

Design, Synthesis and Biological Evaluation of Ethyl 5-(1-benzyl-1H-indol-5-yl) Isoxazole-3-Carboxylates as Antimycobacterial Agents.

The continued prevalence of drug-resistant Mycobacterium tuberculosis (Mtb) strains, particularly against first-line antitubercular (anti-TB) drugs, presents an impending public health threat that necessitates the exploration and development of New Chemical Entities (NCEs). In search of new anti-TB leads, a library of ethyl 5-(1-benzyl-1H-indol-5-yl) isoxazole-3-carboxylates were generated through a strategy of scaffold hopping from the proven isoxazole-3-carboxylate-based anti-TB pharmacophore. We evaluated their antibacterial potential against a panel of pathogenic bacteria and Mtb H37Rv strains. The majority of the compounds exhibited notable in vitro efficacy against the H37Rv strains (MIC 0.25 to 16 μg/mL) and were not cytotoxic with a Selectivity Index (SI) >10. Compound 5e (3,4-dichlorobenzyl substituent) was found to be optimally active in the lot (MIC 0.25 μg/mL) and SI >200. It also displayed equipotent activity against drug-resistant Mtb (DR-Mtb) strains. In addition, it demonstrated concentration-dependent bactericidal activity in a time-kill kinetic assay similar to first-line anti-TB drugs besides exhibiting synergistic activity with Streptomycin. Moreover, it complies with the drug-likeness characteristic, making it a promising candidate for further exploration as a probable anti-TB lead.

Thymol-Loaded Zinc Ferrite Nanoparticles: A Novel Carrier for Enhanced Antimicrobial and Antibiofilm Activity against M. smegmatis through ROS-Mediated Mechanism.

Tuberculosis (TB) remains a persistent global health challenge, with an increasing incidence of cases and limitations in current treatment strategies. Traditional therapy involves long drug treatments that can cause side effects and lead to drug-resistant strains, making treatment less effective. This study aimed to explore the therapeutic potential of a novel nanoparticle-based delivery system for Thymol (THY), a natural antibacterial bioactive molecule, to combat Mycobacterium smegmatis, a model organism for Mycobacterium tuberculosis. A nanoparticle-based delivery system was developed using biocompatible Thymolconjugated Chitosan Zinc Ferrite Nanoparticles (THY-CH-ZnFe2O4 NPs). The nanoconjugates were characterized for their morphological and chemical properties. The characterization of synthesised nanoparticles showed THY-CH-ZnFe2O4 NPs to exhibit enhanced biocompatibility and antibacterial activity against M. smegmatis compared to THY alone. The nanoconjugates induced Reactive Oxygen Species (ROS)-mediated damage to the bacterial cell membrane, effectively inhibiting bacterial replication, dormancy, and biofilm formation. Additionally, the nanoconjugates demonstrated low cytotoxicity towards the human kidney cell line. The study's findings highlighted a new direction for developing nanoparticle-based antimycobacterial agents with a wide application in treating TB and other bacterial diseases. The THY-CH-ZnFe2O4 NPs show promise as a safe and effective therapeutic agent, offering a potential solution to the limitations of current TB treatment strategies.

Antimicrobial, and Antitubercular Evaluation with ADME and Molecular Docking Studies and DFT Calculatıons of (Z)-3-((1-(5-amino-1,3,4-thiadiazol-2-yl)-2-Phenylethyl)imino)-5-nitroindolin-2-one Schiff Base

(Z)-3-((1-(5-Amino-1,3,4-Thiadiazol-2-yl)-2-Phenylethyl)İmino)-5-nitroindolin-2-one Schiff Base compound (ATSB) have lately gained popularity, so the concept that these compounds should be researched has been highlighted. ATSB molecule, a unique Schiff base complex, was selected for molecular modeling research for publication in the literature. Initially, dependent density functional theory (DFT) computations were performed on ATSB molecule (geometry optimization, HOMO-LUMO, MEPS maps, dipole moment calculations, NBO analysis, and Mulliken Atomic Charges). Additionally, ADME analyzes have been carried out for the ATSB molecule and the color regions are given separately. Schiff bases have been shown to have an important role in antibacterial and antituberculosis medication illness and drug repair. Finally, in our investigation, molecular docking analysis ments were performed individually for ATSB molecule with two distinct enzymes (5V3X and 5V3Y), docking scores and receptor models have been given.

Inhibitors of acetohydroxyacid synthase as promising agents against non-tuberculous mycobacterial diseases.

Acetohydroxyacid synthase (AHAS), exclusively present in microorganisms and plants, is a promising target for several herbicides due to its catalytic role in the branched-chain amino acid biosynthetic pathway. Previous studies have shown that K13787, a pyrazolopyrimidine sulfonamide AHAS inhibitor, was moderately effective against pulmonary infection caused by M. tuberculosis and nontuberculous mycobacteria (NTM). In this study, we synthesized various structural derivatives of K13787 based on the molecular docking studies and assessed their MICs against mycobacteria species. Among the synthetic compounds screened, K13787, along with KNT2077 and KNT2099, exhibited inhibitory efficacy against M. avium and M. abscessus, including CLR-resistant NTM species. Notably, these compounds displayed a synergistic effect (FIC ≤ 0.5) when combined with CLR against M. avium and M. abscessus. Our findings suggest that these newly identified AHAS-targeted compounds hold promise as lead candidates for novel antimycobacterial agents against NTM infections. Considering the structure-activity relationship, K13787, KNT2077, and KTN2099 emerge as potential treatments for NTM species.

P68 Safety in patients with latent tuberculosis who received concomitant anti-tuberculosis medications: analysis of 11 studies of guselkumab in psoriatic disease

Abstract Treatments for psoriatic disease, including TNF inhibitors (TNFi), increase the risk of latent tuberculosis infection (LTBI) activation, and TB screening before initiating systemic therapy is recommended. Safety outcomes in LTBI+ patients with moderate-to-severe psoriasis (PsO) or active psoriatic arthritis (PsA) on guselkumab for up to 5 years were pooled from 11 Phase 2/3 studies (7 PsO, 4 PsA). Guselkumab was generally administered as 100 mg subcutaneous injections at Week (W)0, W4, then every 8 weeks (q8w) in PsO studies and W0, W4, then every 4 weeks (q4w) or q8w in PsA studies. Patients randomized to placebo crossed over to guselkumab at W16 (in PsO) or W24 (in PsA). Patients with active TB at screening were excluded. LTBI+ patients were eligible if appropriate LTBI treatment was initiated before/with the first study-drug administration or appropriate treatment was completed within 5 years. Safety was reported annually during the placebo-controlled period, and through the end of follow-up (PsO ≤5 years; PsA ≤2 years). LTBI+ patients were from Asia-Pacific − 10.0%(70/697), Western Europe − 7.3%(51/698), Eastern Europe − 7.3%(179/2453), and North America − 5.3%(74/1407). LTBI treatment initiated before [88.2% (330/374)], with [6.1% (23/374)], or after [5.6% (21/374)] first study drug dose [median −8.0 days (interquartile range, IQR, −20.0 to −2.0)]. LTBI treatments included isoniazid (82.1%), rifampicin (11.8%), and other medications (17.4%); 89.8% received monotherapy. No new-onset TB or LTBI activation was observed in any guselkumab-treated patient. Adverse events (AEs) and serious AEs rates were similar for guselkumab- and placebo-treated patients in LTBI+ and LTBI− groups during the placebo-controlled period; cumulative rates were comparable between guselkumab-treated LTBI+ and LTBI− patients through the end of follow-up. Through Year 1, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations were more common in LTBI+ vs. LTBI− group; ≤2% of LTBI+ patients had Grade 3 elevations (no Grade 4) vs. 0.5% of LTBI− patients. From Years 1–5 [after ∼98% of LTBI+ patients completed prophylaxis (median 185 days, IQR 124–274)], the proportions of LTBI+ and LTBI− patients with elevated ALT/AST were similar. No cases of new-onset TB or LTBI activation were observed in up to 5 years of guselkumab treatment and safety was generally similar in LTBI+ and LTBI− patients. Consistent with the known safety of LTBI medications, ALT/AST elevations were more common in LTBI+ vs. LTBI− patients through Year 1; however, ALT/AST elevation rates were generally similar post-LTBI treatment. The absence of observed TB risk in guselkumab-treated patients suggests guselkumab may be a better treatment option than TNFi in high-risk patients, including those in TB-endemic regions.

Unveiling the Antimycobacterial Potential of Novel 4-Alkoxyquinolines: Insights into Selectivity, Mechanism of Action, and In Vivo Exposure.

This work presents a comprehensive investigation into the design, synthesis, and evaluation of a novel series of 4-alkoxyquinolines as potential antimycobacterial agents. The design approach, which combined molecular simplification and chain extension, resulted in compounds with potent and selective activity against both drug-susceptible and multidrug-resistant Mycobacterium tuberculosis strains. The lead molecule, targeting the cytochrome bc1 complex, exhibited favorable kinetic solubility and remarkable chemical stability under acidic conditions. Despite in vitro ADME evaluations showing low permeability and high metabolism in rat microsomes, the lead compound exhibited bacteriostatic activity in a murine macrophage model of TB infection and demonstrated promising in vivo exposure following gavage in mice, with an AUC0-t of 127.5 ± 5.7 μM h. To the best of our knowledge, for the first time, a simplified structure from 2-(quinolin-4-yloxy)acetamides has shown such potential. These findings suggest a new avenue for exploring this chemical class as a source of antituberculosis drug candidates.

Macrophage Activation Syndrome in a Patient with Systemic Lupus Erythematous Triggered by Tuberculous Meningitis.

Hemophagocytic lymphohistiocytosis (HLH), is characterized by systemic uncontrolled inflammation resulting from immune dysregulation secondary to various triggers, including genetics, infections, autoimmune diseases, and malignancies. Macrophage activation syndrome (MAS) is an immune dysregulation phenomenon, in which an underlying rheumatological disease is present. We report a rare, interesting case of a middle-aged female, with a systemic lupus erythematosus (SLE) flare complicated by macrophage activation syndrome (MAS), in which tuberculous meningitis (TBM) was the identified trigger. A 48-year-old female with an African ethnic background, diagnosed with SLE, presented with a 2-week history of high-grade fever, cough, and worsening arthralgia. She was initially admitted with suspected SLE flare secondary to community acquired pneumonia and was started on broad-spectrum antibiotics. Later during her hospital stay, she underwent extensive workup because of her clinical condition, as she had continuous spikes of fever, progressive cytopenia, accompanied with acute confusion state despite treatment. She was ultimately diagnosed with SLE flare complicated by MAS secondary to TBM in view of persistent fever, neuropsychiatric symptoms, hyperferritinemia and hypertriglyceridemia, supported by bone marrow aspiration findings, a tuberculosis (TB) positive contact and supporting cerebrospinal fluid analysis suggestive of TBM. She was immediately started on pulse doses of steroids and anti-tuberculosis medications in which significant clinical improvement was observed. She was discharged home, with continuity of care done at the outpatient department in addition to continuity of physical rehabilitation. Given the wide range of clinical presentations and similarities between SLE and the life-threatening MAS, it is essential to maintain a high level of suspicion to establish the diagnosis and promptly start the necessary treatment to ensure better clinical and survival outcomes. The wide range of clinical presentation of hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) makes it a challenging diagnosis. Hence, a high index of suspicion is necessary to establish the diagnosis and promptly start the necessary treatment.The mainstay of treatment is the early identification and management of the underlying etiology of MAS along with high-dose glucocorticoids and other immunosuppressive therapy targeting the immune dysregulation pathway.

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.