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1.
Front Public Health ; 12: 1405358, 2024.
Article in English | MEDLINE | ID: mdl-39086797

ABSTRACT

Objectives: This study aimed to investigate the epidemiological and drug resistance (DR) characteristics of extrapulmonary tuberculosis (EPTB) in South-Central China. Methods: EPTB inpatients who were culture-positive for Mycobacterium tuberculosis were retrospectively included in a study at a provincial TB hospital in Hunan, a province in South-Central China, from January 2013 to December 2021. Demographic, clinical, and drug susceptibility data were retrieved from TB treatment records. Descriptive statistical methods and a Chi-squared test were used to analyze the epidemiological and DR characteristics of EPTB patients. A logistic regression model was used to explore the risk factors of rifampicin-resistant/multidrug-resistant (RR/MDR)-EPTB. Results: A total of 1,324 cases were included. The majority of EPTB patients were in the age range of 20-29 years, were predominantly men (male-to-female ratio: 2.03), and were farmers (65.63%). Most EPTB cases were found in 2013 and 2017 from 2013 to 2021. The most prevalent subtypes of EPTB were lymphatic TB (29.83%, 395/1,324), multiple EPTB (20.85%, 276/1,324), and musculoskeletal TB (14.65%, 194/1,324). Musculoskeletal TB and genitourinary TB predominantly presented as exclusive EPTB forms, while lymphatic TB and pharyngeal/laryngeal TB often co-occurred with pulmonary TB (PTB). Drug susceptibility testing results showed that total DR rates (resistance to any of RFP, isoniazid [INH], streptomycin [STR], and/or ethambutol [EMB]) and RR/MDR rates in EPTB were 25.23% and 12.39%, respectively. Musculoskeletal TB exhibited the highest rates of total DR (31.40%), INH resistance (28.90%), STR resistance (20.10%), EMB resistance (6.20%), MDR (13.90%), and poly-DR (6.70%). The multivariable logistic regression model showed that patients aged from 20 to 59 years (compared to those aged 10 years), workers (compared to retirees), and EPTB patients from the south and west of Hunan (compared to those from the east of Hunan) were at an increased risk of developing RR/MDR EPTB (all OR values > 1). Conclusion: Our study provided a detailed account of the epidemiological and DR characteristics of EPTB in Hunan province, China. The significant DR rates, particularly in musculoskeletal TB cases, highlight the need for timely diagnosis, effective drug susceptibility testing, and the development of more effective treatment regimens for EPTB, especially targeting musculoskeletal TB treatments.


Subject(s)
Antitubercular Agents , Mycobacterium tuberculosis , Humans , Male , Female , China/epidemiology , Adult , Middle Aged , Retrospective Studies , Mycobacterium tuberculosis/isolation & purification , Mycobacterium tuberculosis/drug effects , Antitubercular Agents/therapeutic use , Antitubercular Agents/pharmacology , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Multidrug-Resistant/drug therapy , Risk Factors , Young Adult , Adolescent , Rifampin/therapeutic use , Rifampin/pharmacology , Tuberculosis/epidemiology , Tuberculosis/drug therapy , Aged , Child , Microbial Sensitivity Tests , Tuberculosis, Extrapulmonary
2.
J Clin Immunol ; 44(8): 171, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39102004

ABSTRACT

PURPOSE: Chronic granulomatous disease (CGD) is an inherited immunodeficiency caused by pathogenic variants of genes encoding the enzyme complex NADPH oxidase. In countries where tuberculosis (TB) is endemic and the Bacillus Calmette-Guérin (BCG) vaccine is routinely administered, mycobacteria are major disease-causing pathogens in CGD. However, information on the clinical evolution and treatment of mycobacterial diseases in patients with CGD is limited. The present study describes the adverse reactions to BCG and TB in Mexican patients with CGD. METHODS: Patients with CGD who were evaluated at the Immunodeficiency Laboratory of the National Institute of Pediatrics between 2013 and 2024 were included. Medical records were reviewed to determine the clinical course and treatment of adverse reactions to BCG and TB disease. RESULTS: A total of 79 patients with CGD were included in this study. Adverse reactions to BCG were reported in 55 (72%) of 76 patients who received the vaccine. Tuberculosis was diagnosed in 19 (24%) patients. Relapse was documented in three (10%) of 31 patients with BGC-osis and six (32%) of 19 patients with TB, despite antituberculosis treatment. There was no difference in the frequency of BCG and TB disease between patients with pathogenic variants of the X-linked CYBB gene versus recessive variants. CONCLUSIONS: This report highlights the importance of considering TB in endemic areas and BCG complications in children with CGD to enable appropriate diagnostic and therapeutic approaches to improve prognosis and reduce the risk of relapse.


Subject(s)
BCG Vaccine , Granulomatous Disease, Chronic , NADPH Oxidase 2 , Tuberculosis , Humans , Granulomatous Disease, Chronic/diagnosis , Granulomatous Disease, Chronic/epidemiology , Granulomatous Disease, Chronic/complications , BCG Vaccine/adverse effects , Male , Female , Child , Tuberculosis/epidemiology , Tuberculosis/immunology , Child, Preschool , Infant , Adolescent , NADPH Oxidase 2/genetics , Cohort Studies , Mycobacterium bovis , Mexico/epidemiology , Antitubercular Agents/therapeutic use , NADPH Oxidases/genetics
3.
Indian J Tuberc ; 71(3): 238-241, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39111930

ABSTRACT

BACKGROUND: Laryngeal involvement is rare in tuberculosis, representing around 1% of all cases of this infection worldwide. Given the larynx' location in the airway, this form of tuberculosis is of particular importance because it is highly contagious. With our hospital being in a high tuberculosis burden area, we propose to characterize the clinical presentation, evolution, and laryngoscopy findings of a series of laryngeal tuberculosis cases in order to reduce misdiagnosis. METHODS: Epidemiological and clinical data from 10 patients diagnosed with laryngeal tuberculosis in the Otorhinolaryngology department of (Blinded for manuscript) between January 2011 and December 2021 were retrieved and analyzed. RESULTS: There were eight males and two females. Seven patients had a history of smoking and alcohol abuse and four had silicosis. Hoarseness was the most reported symptom (n = 9). The most frequent site of involvement were the true vocal cords (n = 6). All patients but one had concomitant active pulmonary tuberculosis. Patients had full resolution of laryngeal symptoms between 4 and 16 weeks after initiating antituberculosis treatment. CONCLUSION: Laryngeal tuberculosis is indeed a great deceiver. On one hand it can look like a simple polypoid lesion or simulate laryngopharyngeal reflux; but on the other hand its risk factors, symptoms and appearance simulate laryngeal carcinoma like no other. Since most patients present with concomitant pulmonary tuberculosis, all suspect laryngeal lesions should perform a chest radiograph prior to rigid laryngoscopy. Antituberculosis treatment is effective in both alleviating symptoms and reducing the risk of transmission.


Subject(s)
Hoarseness , Laryngoscopy , Tuberculosis, Laryngeal , Tuberculosis, Pulmonary , Humans , Tuberculosis, Laryngeal/diagnosis , Tuberculosis, Laryngeal/drug therapy , Male , Female , Adult , Middle Aged , Hoarseness/etiology , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/drug therapy , Antitubercular Agents/therapeutic use , Aged , Vocal Cords/pathology , Smoking/adverse effects , Retrospective Studies , Diagnosis, Differential , Laryngopharyngeal Reflux/diagnosis
4.
Indian J Tuberc ; 71(3): 337-343, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39111944

ABSTRACT

BACKGROUND: Tuberculosis disease epidemiology is closely related to social and economic conditions which make its prevention, control and cure challenging. Early diagnosis and adequate treatment will help to prevent various tuberculosis related morbidities. Factors such as adverse effects of drugs, transportation cost, family support, distance to the treatment center, personal habits, co morbid conditions, and patients' multiple obligations concerning to their employment, family and society have an impact on the treatment outcomes. OBJECTIVE: To know the factors affecting tuberculosis treatment outcome among newly diagnosed tuberculosis patients. MATERIALS AND METHODS: A total of 261 Tuberculosis patients registered in NTEP under District tuberculosis centre were enrolled using universal sampling method. First follow up was done at the end of intensive phase i.e. End of 2 months. Second follow up was done after completion of treatment i.e., End of 6th month. RESULTS: Majority 59% participants were diagnosed as smear negative at 2nd month follow up and 45.21% and 28.73% participants were diagnosed as cured and treatment completed respectively at 6th month follow up. 73.95% participants had successful outcome. Multivariate logistic regression analysis showed that treatment outcomes of tuberculosis were affected by type of house (pucca house), presence of cough, past history of tuberculosis, family support, supervision by family and support of supervisor. CONCLUSION: Overall treatment success rate was 73.95%. The contributing factors for successful outcome of tuberculosis were age, past history of TB, type of house, presence of cough and fever, weight gain, family support, supervision by family and support of supervisor.


Subject(s)
Antitubercular Agents , Humans , Male , Female , Adult , Antitubercular Agents/therapeutic use , Longitudinal Studies , Treatment Outcome , Middle Aged , Young Adult , India/epidemiology , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/epidemiology , Adolescent , Tuberculosis/diagnosis , Tuberculosis/drug therapy , Tuberculosis/epidemiology , Cough/etiology , Age Factors , Logistic Models , Social Support
5.
Indian J Tuberc ; 71(3): 331-336, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39111943

ABSTRACT

BACKGROUND: Tuberculous mastitis (TBM), is an uncommon form of extra-pulmonary tuberculosis. Clinical and radiological overlap of tuberculous mastitis with malignancy and other granulomatous conditions, along with its paucibacillary nature, make it a diagnostic challenge. In our study, we aim to assess the radiological response of microbiologically negative granulomatous mastitis cases to anti-tuberculous treatment (ATT) in an endemic country. METHODS: Eighty-seven cases demonstrating granulomatous lesions on breast biopsy were identified. Of these, 49 patients who were treated with ATT and had at least two serial ultrasound follow-ups were included in our study. Mammogram and ultrasound were used for initial imaging. Subsequently, ultrasound was used for serial follow-up. Mantoux skin test, acid fast staining and histological examination of tissue sample were the other investigations used. RESULTS: Radiologically, on ultrasound, well-circumscribed hypoechoic masses were noted in 18 patients, followed by ill-defined collections with tubular extensions in 15 cases, abscesses in 8, and a focal heterogeneity in 8 patients. Following ATT, 17 patients showed radiological resolution in 4 weeks, 18 of them at 3 months, and nine of them in 6 months. CONCLUSION: Excellent and prompt radiological response to ATT, indicates the need for a high degree of suspicion for tuberculous mastitis (TBM), in endemic countries, even though microbiological tests may turn out negative.


Subject(s)
Antitubercular Agents , Granulomatous Mastitis , Humans , Female , Granulomatous Mastitis/drug therapy , Granulomatous Mastitis/diagnostic imaging , Antitubercular Agents/therapeutic use , Adult , Middle Aged , Mammography , Ultrasonography, Mammary , India/epidemiology , Young Adult , Tuberculosis/drug therapy , Tuberculosis/epidemiology , Treatment Outcome , Endemic Diseases
6.
Indian J Tuberc ; 71(3): 370-373, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39111950

ABSTRACT

Tuberculosis. a disease of great public concern, is spread through inhalation of micro-droplets from an infected person. Despite lungs being the primary site, there may be multisystemic involvement, very rarely involving bone marrow, a dreaded manifestation of disseminated tuberculosis, associated with high mortality and morbidity. We report a case of tuberculosis of bone marrow with concomitant secondary hemophagocytic lympho-histiocytosis, bringing into light the importance of clinical suspicion and evaluation of bone marrow being a primary site of involvement in patients of disseminated tuberculosis.


Subject(s)
Jaundice, Obstructive , Lymphohistiocytosis, Hemophagocytic , Humans , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/complications , Jaundice, Obstructive/etiology , Jaundice, Obstructive/diagnosis , Male , Bone Marrow/pathology , Diagnosis, Differential , Bone Marrow Diseases/complications , Bone Marrow Diseases/diagnosis , Tuberculosis/diagnosis , Tuberculosis/complications , Antitubercular Agents/therapeutic use , Adult
7.
Indian J Tuberc ; 71(3): 353-357, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39111946

ABSTRACT

Tuberculosis and Mental Illness (TB-MI) often co-occur with a varying range of interactions of both. The rising incidence of both in Low- and Middle-income countries (LMICs) is an emergent public health problem with accompanying higher morbidity and complications in management. The objective of this review is to gather insights into how healthcare providers can enhance their support for patients with TB-MI, to improve treatment adherence and overall health outcomes. Addressing the complexities of TB-MI treatment requires a multi-component approach that includes psychological interventions, monitoring the course of mental health comorbidities, patient education, looking into barriers to adherence, and involving healthcare providers. These coupled with increased patient awareness, integrated care model, patient education and empowerment, simplified treatment approaches, social support programs, and sensitizing healthcare providers can decrease the burden on the healthcare system while improving patient outcomes.


Subject(s)
Mental Disorders , Humans , Mental Disorders/therapy , Tuberculosis/therapy , Tuberculosis/epidemiology , Antitubercular Agents/therapeutic use , Treatment Adherence and Compliance , Medication Adherence , Social Support , Comorbidity
9.
J Enzyme Inhib Med Chem ; 39(1): 2388207, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39140692

ABSTRACT

The crystallographic structure of the FolB enzyme from Mycobacterium tuberculosis (MtFolB), complexed with its inhibitor 8-mercaptoguanine (8-MG), was elucidated at a resolution of 1.95 Å. A novel series of S8-functionalized 8-MG derivatives were synthesised and evaluated as in vitro inhibitors of dihydroneopterin aldolase (DHNA, EC 4.1.2.25) activity of MtFolB. These compounds exhibited IC50 values in the submicromolar range. Evaluation of the activity for five compounds indicated their inhibition mode and inhibition constants. Molecular docking analyses were performed to determine the enzyme-inhibitor intermolecular interactions and ligand conformations upon complex formation. The inhibitory activities of all compounds against the M. tuberculosis H37Rv strain were evaluated. Compound 3e exhibited a minimum inhibitory concentration in the micromolar range. Finally, Compound 3e showed no apparent toxicity in both HepG2 and Vero cells. The findings presented herein will advance the quest for novel, specific inhibitors targeting MtFolB, an attractive molecular target for TB drug development.


Subject(s)
Aldehyde-Lyases , Antitubercular Agents , Dose-Response Relationship, Drug , Enzyme Inhibitors , Microbial Sensitivity Tests , Mycobacterium tuberculosis , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/enzymology , Antitubercular Agents/pharmacology , Antitubercular Agents/chemical synthesis , Antitubercular Agents/chemistry , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Humans , Structure-Activity Relationship , Aldehyde-Lyases/antagonists & inhibitors , Aldehyde-Lyases/metabolism , Aldehyde-Lyases/chemistry , Vero Cells , Molecular Structure , Crystallography, X-Ray , Chlorocebus aethiops , Animals , Guanine/pharmacology , Guanine/chemistry , Guanine/analogs & derivatives , Guanine/chemical synthesis , Molecular Docking Simulation , Hep G2 Cells , Models, Molecular
10.
BMC Infect Dis ; 24(1): 807, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39123148

ABSTRACT

BACKGROUND: This dual burden of tuberculosis (TB) and diabetes mellitus (DM) has become a global public health concern. This study aims to compare drug resistance in drug-resistant tuberculosis (DR-TB) patients with and without DM and analyse the risk factors of multidrug-resistant tuberculosis (MDR-TB). METHODS: A total of 893 DR-TB patients were admitted to Wenzhou Central Hospital between January 2018 and December 2022. After excluding 178 cases with incomplete clinical and laboratory data, 715 patients were included in the study. These patients were then categorized into two groups based on the presence of type 2 DM: the DM group (160 cases) and the non-DM group (555 cases). Demographic information, baseline clinical characteristics, laboratory and imaging test results, clinical diagnoses, and other relevant data were collected for analysis. Statistical analysis was conducted on demographic information, clinical parameters, drug resistance spectrum, and risk factors for multidrug resistance. RESULTS: In both the DM and non-DM groups, the order of resistance to first-line anti-tuberculosis drugs is isoniazid, streptomycin, rifampicin, and ethambutol. There is no significant difference in the proportion of mono-resistant tuberculosis, polydrug-resistant tuberculosis, and multidrug-resistant tuberculosis between the two groups (P > 0.05). The prevalence of MDR-TB in both groups shows a downward trend between 2018 and 2022, but the trend is not statistically significant (P > 0.05). Among patients without DM, residence in rural areas, retreatment of tuberculosis, pulmonary cavity, and uric acid ≥ 346 µmol/L are identified as independent risk factors for MDR-TB. Among patients with DM, residence in rural areas, retreatment of tuberculosis, pulmonary cavity, and HbA1c ≥ 9.8% were identified as independent risk factors for MDR-TB. CONCLUSION: Isoniazid is the most resistant drug among DR-TB patients with and without DM. There is no statistically significant difference in drug resistance patterns between the two groups. Some progress has been made in the prevention and control of DR-TB in this area, but the effect is not very significant. There are differences in the risk factors of MDR-TB between patients with and without DM.


Subject(s)
Antitubercular Agents , Tuberculosis, Multidrug-Resistant , Humans , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Multidrug-Resistant/microbiology , Male , Female , Middle Aged , Adult , Antitubercular Agents/therapeutic use , Antitubercular Agents/pharmacology , Risk Factors , Mycobacterium tuberculosis/drug effects , China/epidemiology , Aged , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Drug Resistance, Multiple, Bacterial , Retrospective Studies , Microbial Sensitivity Tests
11.
BMC Pulm Med ; 24(1): 385, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39123152

ABSTRACT

BACKGROUND: The aim of our study was to investigate serum chitotriosidase level in tuberculosis patients, its relationship with microbiological and clinical parameters, and response to treatment. MATERIALS AND METHODS: This longitudinal panel study included 149 patients with confirmed TB disease. Serum chitotriosidase activity was measured at the beginning and the end of treatment. Factors associated with chitotriosidase activity were explored using univariate and multivariable logistic regression analysis. RESULTS: Out of 149 study participants, 71(47.7%) were female. The mean age was 53.0 (SD = 18.2). Majority of cases were new 118(79.2), predominantly 145 (97.3%) having pulmonary tuberculosis. More than half of the patients were sputum smear positive 91 (61.1%) while culture positive in 146 (98%) of them. According to radiological findings, cavitary lesions were found in 92 (63.4%) patients. Anti TB treatment was associated with significant decrease in serum chitotriosidase level (< 0.001). New TB treatment (OR = 4.41%;95% CI = 1.20-9.89), and cavitary lesions (OR = 3.86;95%CI = 0,59-26.57) were found to be significantly associated with decrease of chitotriosidase activity. CONCLUSIONS: The results of our study showed that serum chitotriosidase values are strong biomarkers for starting anti TB treatment and for treatment monitoring, since decrease in serum chitotriosidase level can predict favorable treatment response in patients with tuberculosis. Further studies are needed to explore these, and other factors associated with chitotriosidase activity among tuberculosis patients.


Subject(s)
Antitubercular Agents , Hexosaminidases , Sputum , Tuberculosis, Pulmonary , Humans , Female , Hexosaminidases/blood , Male , Middle Aged , Antitubercular Agents/therapeutic use , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/blood , Adult , Aged , Sputum/microbiology , Longitudinal Studies , Serbia , Logistic Models , Treatment Outcome , Biomarkers/blood , Multivariate Analysis , Mycobacterium tuberculosis/isolation & purification
12.
Sci Rep ; 14(1): 18458, 2024 08 09.
Article in English | MEDLINE | ID: mdl-39122738

ABSTRACT

Tuberculosis (TB) preventive treatment (TPT) effectively prevents the progression from TB infection to TB disease. This study explores factors associated with TPT non-completion in Cambodia using 6-years programmatic data (2018-2023) retrieved from the TB Management Information System (TB-MIS). Out of 14,262 individuals with latent TB infection (LTBI) initiated with TPT, 299 (2.1%) did not complete the treatment. Individuals aged between 15-24 and 25-34 years old were more likely to not complete the treatment compared to those aged < 5 years old, with aOR = 1.7, p = 0.034 and aOR = 2.1, p = 0.003, respectively. Individuals initiated with 3-month daily Rifampicin and Isoniazid (3RH) or with 6-month daily Isoniazid (6H) were more likely to not complete the treatment compared to those initiated with 3-month weekly Isoniazid and Rifapentine (3HP), with aOR = 2.6, p < 0.001 and aOR = 7, p < 0.001, respectively. Those who began TPT at referral hospitals were nearly twice as likely to not complete the treatment compared to those who started the treatment at health centers (aOR = 1.95, p = 0.003). To improve TPT completion, strengthen the treatment follow-up among those aged between 15 and 34 years old and initiated TPT at referral hospitals should be prioritized. The national TB program should consider 3HP the first choice of treatment.


Subject(s)
Antitubercular Agents , Isoniazid , Latent Tuberculosis , Rifampin , Humans , Cambodia/epidemiology , Adolescent , Adult , Female , Male , Young Adult , Antitubercular Agents/therapeutic use , Retrospective Studies , Isoniazid/therapeutic use , Rifampin/therapeutic use , Rifampin/analogs & derivatives , Child , Latent Tuberculosis/drug therapy , Latent Tuberculosis/epidemiology , Latent Tuberculosis/prevention & control , Child, Preschool , Tuberculosis/prevention & control , Tuberculosis/epidemiology , Tuberculosis/drug therapy , Middle Aged , Infant
13.
Sci Rep ; 14(1): 18550, 2024 08 09.
Article in English | MEDLINE | ID: mdl-39122761

ABSTRACT

Conversion of sputum from positive to negative is one of the indicators to evaluate the efficacy of anti-tuberculosis treatment (ATT). We investigate the factors associated with delayed sputum conversion after 2 or 5 months of ATT from the perspectives of bacteriology and genomics. A retrospective study of sputum conversion in sputum positive 1782 pulmonary tuberculosis (PTB) was conducted from 2021 to 2022 in Beijing, China. We also designed a case-matched study including 24 pairs of delayed-sputum-conversion patients (DSCPs) and timely-sputum-conversion patients (TSCPs), and collect clinical isolates from DSCPs before and after ATT and initial isolates of TSCPs who successfully achieved sputum conversion to negative after 2 months of ATT. A total of 75 strains were conducted drug sensitivity testing (DST) of 13 anti-TB drugs and whole-genome sequencing (WGS) to analyze the risk factors of delayed conversion and the dynamics changes of drug resistance and genomics of Mycobacterium tuberculosis (MTB) during ATT. We found TSCPs have better treatment outcomes and whose initial isolates show lower levels of drug resistance. Clinical isolates of DSCPs showed dynamically changing of resistance phenotypes and intra-host heterogeneity. Single nucleotide polymorphism (SNP) profiles showed large differences between groups. The study provided insight into the bacteriological and genomic variation of delayed sputum conversion. It would be helpful for early indication of sputum conversion and guidance on ATT.


Subject(s)
Antitubercular Agents , Genomics , Mycobacterium tuberculosis , Sputum , Tuberculosis, Pulmonary , Humans , Tuberculosis, Pulmonary/microbiology , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/diagnosis , Sputum/microbiology , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/isolation & purification , Mycobacterium tuberculosis/drug effects , Antitubercular Agents/therapeutic use , Antitubercular Agents/pharmacology , Male , Adult , Female , Retrospective Studies , Middle Aged , Genomics/methods , Polymorphism, Single Nucleotide , Microbial Sensitivity Tests , Whole Genome Sequencing , Treatment Outcome , Drug Resistance, Bacterial/genetics
14.
Int J Mol Sci ; 25(15)2024 Jul 27.
Article in English | MEDLINE | ID: mdl-39125766

ABSTRACT

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tb), is a major global health issue, with around 10 million new cases annually. Advances in TB immunology have improved our understanding of host signaling pathways, leading to innovative therapeutic strategies. Inflammasomes, protein complexes organized by cytosolic pattern recognition receptors (PRRs), play a crucial role in the immune response to M. tb by activating caspase 1, which matures proinflammatory cytokines IL1ß and IL18. While inflammation is necessary to fight infection, excessive or dysregulated inflammation can cause tissue damage, highlighting the need for precise inflammasome regulation. Drug-resistant TB strains have spurred research into adjunctive host-directed therapies (HDTs) that target inflammasome pathways to control inflammation. Canonical and non-canonical inflammasome pathways can trigger excessive inflammation, leading to immune system exhaustion and M. tb spread. Novel HDT interventions can leverage precision medicine by tailoring treatments to individual inflammasome responses. Studies show that medicinal plant derivatives like silybin, andrographolide, and micheliolide and small molecules such as OLT1177, INF39, CY-09, JJ002, Ac-YVAD-cmk, TAK-242, and MCC950 can modulate inflammasome activation. Molecular tools like gene silencing and knockouts may also be used for severe TB cases. This review explores these strategies as potential adjunctive HDTs in fighting TB.


Subject(s)
Inflammasomes , Mycobacterium tuberculosis , Tuberculosis , Humans , Inflammasomes/metabolism , Inflammasomes/immunology , Mycobacterium tuberculosis/immunology , Tuberculosis/immunology , Tuberculosis/drug therapy , Tuberculosis/microbiology , Animals , Antitubercular Agents/therapeutic use , Antitubercular Agents/pharmacology , Signal Transduction , Host-Pathogen Interactions/immunology
16.
BMC Pediatr ; 24(1): 520, 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39128996

ABSTRACT

BACKGROUND: Children represent a particularly vulnerable demographic in the context of drug-resistant (DR) tuberculosis (TB) due to their increased likelihood of close contact with adults diagnosed with the disease. Approximately 25 000-30 000 children develop DR-TB annually. While treatment success rates for DR-TB in children surpass those in adults, children and adolescents encounter distinct challenges throughout the diagnosis and treatment of DR-TB (including MDR-TB, Pre-XDR TB, and XDR-TB). AIM: To identify current practices in drug administration to children diagnosed with DR-TB where appropriate dosage forms are not available in South Africa. METHOD: An observational study was carried out at the study site to determine how medication prescribed was manipulated and administered by nursing staff to paediatric patients in the wards. RESULTS: The observational study identified 8 drugs used in DR-TB at the study site, where some manipulation to the formulation was necessary to enable administration to paediatric patients. Linezolid and para-aminosalicylic acid are the only drugs available and registered in the South Africa in a formulation that is suitable for administration to paediatric patients. Activities carried out by nursing staff to enable the administration of DR-TB medication included cutting capsules and tablets and dissolving the tablet or capsule contents in distilled water to obtain the required suitable dose. DISCUSSION: Lack of availability of suitable dosage forms for paediatrics patients results in several challenges, such as additional time required for drug preparation, increased time duration of medication administration, and unpalatability of drugs. These challenges may subsequently affect compliance and therapeutic outcomes of the treatment of paediatric patients, especially as outpatients. CONCLUSION: Research needs to focus on the development of appropriate dosage forms for the paediatric population and focus on identifying cases of DR-TB in children. This will assist in building evidence to advocate for registration of child-friendly dosage forms thereby ensuring a sustainable supply of medication.


Subject(s)
Antitubercular Agents , Tuberculosis, Multidrug-Resistant , Humans , South Africa , Child , Administration, Oral , Antitubercular Agents/administration & dosage , Antitubercular Agents/therapeutic use , Tuberculosis, Multidrug-Resistant/drug therapy , Adolescent , Dosage Forms , Linezolid/administration & dosage , Linezolid/therapeutic use , Child, Preschool , Male , Aminosalicylic Acid/administration & dosage , Aminosalicylic Acid/therapeutic use , Female
17.
Pan Afr Med J ; 47: 181, 2024.
Article in English | MEDLINE | ID: mdl-39092023

ABSTRACT

Introduction: tuberculosis (TB) remains a leading cause of death in South Africa. KwaZulu-Natal (KZN) is one of the provinces with a high burden of TB/drug-resistant TB cases and deaths. We determined predictors for mortality among drug-resistant TB patients on treatment in KZN province. Methods: we conducted a retrospective cohort study using secondary data from the Electronic Drug-Resistant Tuberculosis Register. We used a modified Poisson regression model with robust standard errors to determine predictors for drug-resistant TB mortality. Results: of the 7,692 eligible patients, 1,234 (16.0%) died. Males predominated (707, 57.3%) and the median age was 36 years (Interquartlile Range: 29-45 years). The majority (978, 79.2%) were HIV-TB co-infected with 911 (93%) on antiretroviral treatment (ART). The predictors included HIV-TB co-infection without ART (aIRR 3.4; 95% CI: 2.3-5.1), unknown ART status (aIRR: 1.8; 95% CI: 1.4-2.3), aged ≥60 years (aIRR: 2.1; 95% CI: 1.6-2.7), previous drug-resistant TB (aIRR: 1.5; 95% CI: 1.2-1.8) and exposure to second-line drugs (aIRR: 1.7; 95% CI: 1.4-2.0). Other predictors were hospitalization during treatment initiation (aIRR 2.5; 95% CI 2.0-3.1), initiation in other treatment facilities (aIRR: 2.2; 95% CI: 1.6-2.9) and rifampicin-resistant (aIRR: 1.2; 95% CI: 1.1-1.4). Bedaquiline fumarate was a significant protective factor against death (aIRR: 0.5; 95% CI: 0.4-0.5). Conclusion: older age, HIV co-infection without ART, hospitalization for treatment initiation, exposure to second-line drugs and a previous episode of drug-resistant TB were predictors for DR-TB mortality. Early treatment initiation and provision of antiretroviral treatment for all co-infected patients may reduce DR-TB mortality in the Province.


Subject(s)
Antitubercular Agents , Coinfection , HIV Infections , Tuberculosis, Multidrug-Resistant , Humans , Male , Female , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/mortality , Retrospective Studies , Adult , South Africa/epidemiology , Middle Aged , HIV Infections/drug therapy , Antitubercular Agents/administration & dosage , Coinfection/drug therapy , Cohort Studies , Risk Factors , Young Adult , Adolescent , Age Factors
18.
Ann Med ; 56(1): 2386030, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39097795

ABSTRACT

Tuberculosis (TB) continues to pose a significant health challenge worldwide, emphasizing the importance of prompt diagnosis and efficient monitoring of treatment outcomes for effective disease control. Biomarkers have become increasingly important in the realm of TB diagnoses and treatment. The objective of this comprehensive review is to examine the present state of biomarkers employed in the diagnosis of TB, monitoring the response to treatment, and predicting treatment outcomes. In this study, we undertake a comprehensive examination of the diverse biomarkers utilized in TB diagnoses, spanning molecular, immunological, and other novel methodologies. Furthermore, we examine the potential of biomarkers in the context of therapeutic monitoring, assessment of treatment effectiveness, and anticipation of drug resistance. Additionally, this paper presents future prospects regarding the utilization of biomarkers in the therapy of tuberculosis.


Subject(s)
Antitubercular Agents , Biomarkers , Tuberculosis , Humans , Biomarkers/blood , Tuberculosis/diagnosis , Tuberculosis/drug therapy , Antitubercular Agents/therapeutic use , Treatment Outcome , Mycobacterium tuberculosis/isolation & purification , Drug Monitoring/methods
19.
Am J Trop Med Hyg ; 111(2): 251-258, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39116866

ABSTRACT

In tuberculous meningitis (TBM), the meningeal symptoms and their resolution after treatment may be dependent on clinical-radiological severity, cerebrospinal fluid (CSF), and proinflammatory cytokines, and these findings may be associated with outcome. There is a paucity of studies on the resolution of meningitis symptoms in TBM. We report on associations of clinical, magnetic resonance imaging (MRI), laboratory, and proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin 6 (IL-6)] findings with the resolution of meningitis symptoms (RMS), and the impact of RMS duration on the outcome in TBM. Seventy-one patients with TBM were included, and their clinical, laboratory, and MRI findings at baseline were recorded. mRNA profiling of TNF-α and IL-6 was done by reverse transcriptase polymerase chain reaction. The day of RMS (fever, headache, and vomiting) after treatment was noted. Predictors of long duration of RMS (>3 weeks) were evaluated by univariate followed by multivariate analysis. The impact of RMS on 6-month mortality and outcome was analyzed. Patients' median age was 25 years, and 45 (63.4%) were males. After antitubercular treatment, meningeal symptoms resolved in 35 (50.70%) by 21 days and in 90% of patients by 49 days. Longer time of RMS was associated with TBM stage, pretreatment duration, seizure, and hydrocephalus but not with TNF-α and IL-6. Seven (9.8%) patients died at 6 months, and duration of RMS predicted death (hazard ratio = 25.55, 95% CI: 1.108-589.40; P = 0.04).


Subject(s)
Antitubercular Agents , Biomarkers , Interleukin-6 , Magnetic Resonance Imaging , Tuberculosis, Meningeal , Tumor Necrosis Factor-alpha , Humans , Tuberculosis, Meningeal/drug therapy , Tuberculosis, Meningeal/diagnostic imaging , Tuberculosis, Meningeal/cerebrospinal fluid , Male , Female , Adult , Biomarkers/cerebrospinal fluid , Interleukin-6/cerebrospinal fluid , Antitubercular Agents/therapeutic use , Young Adult , Tumor Necrosis Factor-alpha/cerebrospinal fluid , Middle Aged , Adolescent
20.
Top Antivir Med ; 32(3): 492-503, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39142291

ABSTRACT

Several novel antituberculosis agents, including long-acting injectable agents in mouse models, have shown promise in preclinical and early clinical studies. This encouraging news is offset by the failures of a tuberculosis (TB) vaccine to prevent disease recurrence and a 3-month clofazimine-based treatment regimen for drug-susceptible TB. Clinically focused insights regarding TB, mpox, and other HIV-associated infectious complications that were presented at the 2024 Conference on Retroviruses and Opportunistic Infections (CROI) are summarized in this review.


Subject(s)
Antitubercular Agents , HIV Infections , Tuberculosis , Humans , HIV Infections/complications , HIV Infections/drug therapy , Tuberculosis/complications , Tuberculosis/drug therapy , Antitubercular Agents/therapeutic use , AIDS-Related Opportunistic Infections/drug therapy , Animals , Tuberculosis Vaccines
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