New Biginelli adducts were rationalised, via the introduction of selected anti-tubercular (TB) pharmacophores into the dihydropyrimidine (DHPM) ring of deoxythymidine monophosphate (dTMP), the natural substrate of Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt). Repurposing was one of the design rationale strategies for some selected mimics of the designed compounds. The anti-TB activity was screened against the Mtb H37Rv strain where 11a was superior to ethambutol (EMB), and was 9-fold more potent than pyrazinamide (PZA). Additionally, compounds 11b, 4a, 4b, 13a, 13b and 14a elicited higher anti-TB activity than PZA, showing better safety profiles than EMB against RAW 264.7 cells\' growth. The in vitro TMPKmt inhibition assay released compounds 11a, 11b and 13b as the most potent inhibitors. Docking studies presumed the binding modes and molecular dynamics (MD) simulation revealed the dynamic stability of 11a-TMPKmt complex over 100 ns. In silico prediction of the chemo-informatics properties of the most active compounds was conducted.

BACKGROUND: Even though tuberculosis is a common disease among children in developing countries, tuberculous dactylitis is an uncommon form of Skeletal tuberculosis specially with involvement of both the hands and feet.
METHODS: A one-and-a-half-year-old previously healthy female Ethiopian toddler presented to our pediatric outpatient clinic with a history of two-month duration of painful multiple swellings over both her hands and feet. The swelling involved the proximal phalanx of the left index finger, dorsum of the right hand, and dorsum of both feet over the first metatarsal bone. Physical examination, radiologic findings, and histopathology suggested tuberculous dactylitis. The patient was treated with anti-tuberculosis drugs for one year and she showed clinical and radiologic improvement and recovery.
CONCLUSIONS: Tubercular dactylitis should be considered in the differential diagnosis of children from endemic areas presenting with bone and joint pain or swelling. Our experience of a twelve-month course of antitubercular treatment, which is in line with WHO recommendations, for skeletal tuberculosis, showed excellent outcomes.

The BCG vaccine is considered a safe and efficacious vaccine in the prevention of severe forms of tuberculosis. BCG osteomyelitis is a rare complication of the BCG vaccine that occurs in vaccinated young children. We report a case of BCG osteomyelitis in a male toddler, presenting with painful left wrist swelling without preceding fever or systemic symptoms. Radiographic evidence of osteomyelitis in the left wrist was observed. Initial treatment with conventional antibiotics for acute haematogenous osteomyelitis showed no improvement. The diagnosis of Mycobacterium bovis BCG osteomyelitis was confirmed via tissue samples for histopathological examination and mycobacterial cultures. The patient responded well to treatment with oral antituberculous therapy. This case highlights the importance of considering BCG osteomyelitis in the differential diagnosis of unexplained joint swelling in BCG-vaccinated young children.

BACKGROUND: Respiratory microbiota is closely related to tuberculosis (TB) initiation and progression. However, the dynamic changes of respiratory microbiota during treatment and its association with TB progression remains unclear.
METHODS: A total of 16 healthy individuals and 16 TB patients (10 drug-sensitive TB (DS-TB) and 6 drug-resistant TB (DR-TB)) were recruited. Sputum samples were collected at baseline for all anticipants and after anti-TB treatment at Month-6 for TB patients. High throughput 16 S RNA sequencing was used to characterize the respiratory microbiota composition.
RESULTS: Compared to the healthy individuals, TB patients exhibited lower respiratory microbiota diversity (p < 0.05). This disruption was alleviated after anti-TB treatment, especially for DS-TB patients. Parvimonas spp. numbers significantly increased after six months of anti-TB treatment in both DS-TB and DR-TB patients (p < 0.05). Rothia spp. increase during treatment was associated with longer sputum-culture conversion time and worse pulmonary lesion absorption (p < 0.05). Besides, Moraxella spp. prevalence was associated with longer sputum-culture conversion time, while Gemella spp. increase was associated with worsening resolving of pulmonary lesions (p < 0.05).
CONCLUSIONS: Dynamic changes of respiratory microbiota during anti-TB treatment is closely related to TB progression. The involvement of critical microorganisms, such as Parvimonas spp., Rothia spp., Moraxella, and Gemella spp., appears to be associated with pulmonary inflammatory conditions, particularly among DR-TB. These microorganisms could potentially serve as biomarkers or even as targets for therapeutic intervention to enhance the prognosis of tuberculosis patients.

BACKGROUND: Tuberculosis (TB) is a second major global public health problem and the leading infectious cause of death in Ethiopia. Patients under directly observed treatment short-courses (DOTs) have a higher treatment success rate and reduced drug resistance. A successful treatment outcome and adherence to the treatment are related to patient satisfaction with the DOT strategy. Client satisfaction is one of the indicators of the quality of care. In this perspective, there were limited studies in Ethiopia related to patient satisfaction with the DOTs strategy in the prevention and control of TB to achieve the \'\'END TB Strategy.\'\' Therefore, this study was aimed at identifying the TB patients\' satisfaction with the DOTs strategy and associated factors in Gamo Zone, Southern Ethiopia.
METHODS: An institutional-based cross-sectional study design for quantitative data and a phenomenological approach were employed for qualitative data. The calculated sample size was 374. A systematic random sampling method was used to select study participants. A pre-tested structured interviewer-administered questionnaire for quantitative data and focus group discussions (FGDs) for qualitative data were used for data collection. Bivariable and multivariable analyses were used. The determinants with a p-value < 0.05 were declared to have a significant association with the outcome variable, and an adjusted odd ratio with a 95% confidence interval (CI) was used.
RESULTS: A total of 358 patients participated in the study, with a response rate of 95.72%. The majority of study participants\' ages ranged between 25 and 34 years. The tuberculosis DOT satisfaction rate was 61.17% [56.10-66.25%, 95%CI]. The TB patients who took treatment for 20 weeks or more were 3.97 times [AOR = 3.97; 95% CI (1.55-10.16)] more likely to be satisfied with the DOTs service provided. However, the participants who perceived transport costs as high were 79% [AOR = 0.21; 95% CI (0.06-0.71)] less likely to be satisfied with DOTs. Qualitatively, the participants reported that there was a major problem with laboratory services, which resulted in delays and long appointments to get the results in addition to lack of clean toilets and safe water to swallow medications.
CONCLUSIONS: The satisfaction rate for tuberculosis DOTs observed in this study appears to be relatively lower in comparison to other studies. Availing DOTs service nearby patients to enhance the accessibility of the service is crucial to improving patients\' satisfaction with DOTs service. Reducing laboratory result delays by improving laboratory service is essential to enhancing patients\' satisfaction with DOTs. Moreover, improving toilet services, and availing safe water to swallow medications is recommended to enhancing patients\' satisfaction with DOTs service.

UNASSIGNED: This case emphasizes the value of meticulous observation and regular follow-up of patients receiving rifampicin therapy. The prognosis for complete improvement in renal function in such cases was excellent, with prompt recognition and discontinuation of rifampicin. Teaching patients about these possible adverse effects and encouraging immediate reporting of signs and symptoms are likely to be beneficial because acute kidney injury can manifest itself very quickly after rifampicin is started. Even if renal failure can happen with any dose of rifampicin, primary physicians must have awareness about patients on intermittent or irregular therapy and those who have previously used this medication. It is challenging to determine the prevalence of adverse reactions to common antibiotics where a state- or country-wide reporting system is absent. Along with withdrawal of the causative agent patients were treated with corticosteroids (0.5-1 mg/kg/day) for an average period of 4-12 weeks showing significant recovery of renal function.

Antibiotic tolerance in Mycobacterium tuberculosis reduces bacterial killing, worsens treatment outcomes, and contributes to resistance. We studied rifampicin tolerance in isolates with or without isoniazid resistance (IR). Using a minimum duration of killing assay, we measured rifampicin survival in isoniazid-susceptible (IS, n=119) and resistant (IR, n=84) isolates, correlating tolerance with bacterial growth, rifampicin minimum inhibitory concentrations (MICs), and isoniazid-resistant mutations. Longitudinal IR isolates were analyzed for changes in rifampicin tolerance and genetic variant emergence. The median time for rifampicin to reduce the bacterial population by 90% (MDK90) increased from 1.23 days (IS) and 1.31 days (IR) to 2.55 days (IS) and 1.98 days (IR) over 15-60 days of incubation, indicating fast and slow-growing tolerant sub-populations. A 6 log10-fold survival fraction classified tolerance as low, medium, or high, showing that IR is linked to increased tolerance and faster growth (OR = 2.68 for low vs. medium, OR = 4.42 for low vs. high, p-trend = 0.0003). High tolerance in IR isolates was associated with rifampicin treatment in patients and genetic microvariants. These findings suggest that IR tuberculosis should be assessed for high rifampicin tolerance to optimize treatment and prevent the development of multi-drug-resistant tuberculosis.

UNASSIGNED: neuromeningeal tuberculosis (NMT) is a significant public health challenge in Morocco because of its acute severity and high mortality rates. This study aims to comprehensively evaluate the epidemiological, clinical, therapeutic, and disease progression characteristics of NMT in the Kenitra province.
UNASSIGNED: a retrospective analysis was conducted on the medical records of patients diagnosed with NMT at the Diagnostic Center of Tuberculosis and Respiratory Diseases in Kenitra from 2014 to 2017.
UNASSIGNED: among the 33 identified NMT cases, predominantly males (57.6%) were affected, with an age range of 4-76 years and a median age of 25 years. Extrapulmonary manifestations were prevalent, constituting 78.8% (n=26) of all cases, with meningeal localization in 45.5% (n=15) of confirmed cases. Furthermore, 9.1% (n=3) of cases were associated with unconfirmed cerebral tuberculosis (TB), and 12% (n=4) exhibited miliary TB. Familial transmission and comorbidities were identified as significant factors in disease progression. More than half of the patients received standardized antibacillary treatment during hospitalization, which lasted between 9 and 12 months. Treatment outcomes were generally positive (73%), but a 12% case fatality rate and 15% loss to follow-up were observed.
UNASSIGNED: this study highlights the complex clinical and public health challenges posed by NMT in Morocco. It emphasizes the need for improved health strategies that not only increase public awareness but also enhance the accessibility and quality of diagnostic services and treatment options.

UNASSIGNED: tuberculosis remains a major public health problem, with continuing high levels of prevalence, and mortality. In Niger, the incidence of tuberculosis remains high. This study aims to investigate the epidemiology of pulmonary tuberculosis at the National Anti-Tuberculosis Center of Niamey in Niger.
UNASSIGNED: this study used a quantitative approach with a retrospective and descriptive design. Data were obtained from positive pulmonary tuberculosis cases detected by microscopy on Ziehl-Neelsen stained sputum at the National Anti-Tuberculosis Center (NATC) in Niamey, Niger covered the period between June 2017 and January 2020. 955 pulmonary TB patients were recorded whose diagnosis was based either on clinical-radiological arguments (thus negative microscopy) or positive microscopy. This form was used to collect data recorded in the clinical case registers, registers, and Excel files of the GeneXpert platform of the NATC laboratory.
UNASSIGNED: eighty-nine-point eleven percent (89.11%) of the patients were microscopy-positive. Among the study population, men were the most affected by tuberculosis with 80.03%. The 25-34 age group, representing 23.77%, was the most affected. 6.93% of patients were co-infected with tuberculosis and HIV. All patients were put on treatment, with a therapeutic success rate of 72.38% and a therapeutic failure rate of 10.95%. Among the cases of therapeutic failure, 80.90% had Mycobacterium tuberculosis complex detected and 27.14% were resistant to Rifampicin.
UNASSIGNED: Niger continues to have a tuberculosis epidemic which requires monitoring. Improving the diagnostic system for more effective management of the disease is important for appropriate diagnosis and treatment.

UNASSIGNED: Cutaneous tuberculosis (CTB) and nontuberculous mycobacteria (NTM) infections present considerable diagnostic and therapeutic challenges. This study aims to provide a comprehensive clinicopathological analysis of CTB and NTM infections.
UNASSIGNED: We conducted a retrospective analysis of 103 patients diagnosed with cutaneous tuberculosis (CTB) and nontuberculous mycobacteria (NTM) infections at a Beijing dermatology department from January 2000 to January 2024. Demographic, clinical, histological, and laboratory finding data were collected. Diagnostic methods and histopathological examination were recorded. Treatment regimens and outcomes were reviewed. Descriptive statistics were used to summarize demographic and clinical data, and continuous variables expressed as means and standard deviations (SD), and categorical variables as frequencies and percentages. Statistical analyses were conducted using SPSS version 25.0.
UNASSIGNED: The cohort included 103 patients (40.8% males and 59.2% females), with a mean age of 51.86 years. Common clinical manifestations included nodules (97.1%), erythema (74.8%), and plaques (68.9%). Histological examination revealed hyperkeratosis (68.9%), parakeratosis (23.3%), and extensive neutrophil infiltration (95.1%) were observed. Acid fast bacteria (AFB) stains and nucleic acid tests exhibited respective positivity rates of 39.6% and 52.3%, respectively. Most patients were treated with a combination of three drugs; 77.1% of patients showed improvement, with the cure rate for CTB being 20.0%.
UNASSIGNED: This study highlights the diverse clinical and histological presentations of CTB and NTM infections, emphasizing the need for comprehensive diagnostic approaches. The variability in treatment regimens reflects the complex management of these infections.
UNASSIGNED: The implementation of advanced molecular techniques and standardized treatment protocols is imperative for enhancing diagnostic precision and therapeutic outcomes.