Molecular epidemiology of Mycobacterium tuberculosis in adult Filipino TB-HIV co-infected patients.

BACKGROUND: TB is the leading cause of death from a single infectious disease, particularly among people living with HIV (PLHIV). Molecular epidemiology provides information on prevalent genotypes of Mycobacterium tuberculosis and disease transmission dynamics, which aid in TB control. Identification of mutations that confer drug resistance is essential for the rapid diagnosis of drug-resistant TB, especially in high TB burden settings, like the Philippines.METHODS: This study aimed to determine mutations in M. tuberculosis drug resistance-conferring genes and circulating genotypes in PLHIV. MIRU-VNTR (mycobacterial interspersed repetitive unit-variable number of tandem repeats) typing using a set of 24-loci and sequencing of drug resistance-conferring genes were performed in 22 M. tuberculosis isolates from TB-HIV co-infected patients.RESULTS: The prevalence of resistance to any drug was 31.8%, 18.2% for isoniazid monoresistance, 4.5% for streptomycin monoresistance and 9.1% for multidrug resistance. The identified mutations in the katG, rpoB, pncA, rpsL and gyrA genes have been reported in the literature; none was found in the inhA and embB genes. All isolates belonged to the EAI2-Manila family and were grouped into four clusters based on their phenotypic drug resistance and mutation profiles.CONCLUSION: The use of 24-loci set may be used as a more discriminatory MIRU-VNTR typing in settings where the East African-Indian lineage is predominant, like the Philippines.

3D Deep Learning Angiography (3D-DLA) from C-arm Conebeam CT.

BACKGROUND AND PURPOSE: Deep learning is a branch of artificial intelligence that has demonstrated unprecedented performance in many medical imaging applications. Our purpose was to develop a deep learning angiography method to generate 3D cerebral angiograms from a single contrast-enhanced C-arm conebeam CT acquisition in order to reduce image artifacts and radiation dose. MATERIALS AND METHODS: A set of 105 3D rotational angiography examinations were randomly selected from an internal data base. All were acquired using a clinical system in conjunction with a standard injection protocol. More than 150 million labeled voxels from 35 subjects were used for training. A deep convolutional neural network was trained to classify each image voxel into 3 tissue types (vasculature, bone, and soft tissue). The trained deep learning angiography model was then applied for tissue classification into a validation cohort of 8 subjects and a final testing cohort of the remaining 62 subjects. The final vasculature tissue class was used to generate the 3D deep learning angiography images. To quantify the generalization error of the trained model, we calculated the accuracy, sensitivity, precision, and Dice similarity coefficients for vasculature classification in relevant anatomy. The 3D deep learning angiography and clinical 3D rotational angiography images were subjected to a qualitative assessment for the presence of intersweep motion artifacts. RESULTS: Vasculature classification accuracy and 95% CI in the testing dataset were 98.7% (98.3%-99.1%). No residual signal from osseous structures was observed for any 3D deep learning angiography testing cases except for small regions in the otic capsule and nasal cavity compared with 37% (23/62) of the 3D rotational angiographies. CONCLUSIONS: Deep learning angiography accurately recreated the vascular anatomy of the 3D rotational angiography reconstructions without a mask. Deep learning angiography reduced misregistration artifacts induced by intersweep motion, and it reduced radiation exposure required to obtain clinically useful 3D rotational angiography.

Low-Dose CT for Craniosynostosis: Preserving Diagnostic Benefit with Substantial Radiation Dose Reduction.

BACKGROUND AND PURPOSE: Given the positive impact of early intervention for craniosynostosis, CT is often performed for evaluation but radiation dosage remains a concern. We evaluated the potential for substantial radiation dose reduction in pediatric patients with suspected craniosynostosis. MATERIALS AND METHODS: CT projection data from pediatric patients undergoing head CT for suspected craniosynostosis were archived. Simulated lower-dose CT images corresponding to 25%, 10%, and 2% of the applied dose were created using a validated method. Three neuroradiologists independently interpreted images in a blinded, randomized fashion. All sutures were evaluated by using 3D volume-rendered images alone, and subsequently with 2D and 3D images together. Reference standards were defined by reader agreement by using routine dose and 2D and 3D images. Performance figures of merit were calculated based on reader response and confidence. RESULTS: Of 33 pediatric patients, 21 had craniosynostosis (39 positive sutures and 225 negative sutures). The mean volume CT dose index was 15.5 ± 2.3 mGy (range, 9.69-19.38 mGy) for the routine dose examination. Average figures of merit for multireader analysis ranged from 0.92 (95% CI, 0.90-0.95) at routine pediatric dose to 0.86 (95% CI, 0.79-0.94) at 2% dose using 3D images alone. Similarly, pooled reader figures of merit ranged from 0.91 (95% CI, 0.89-0.95) at routine pediatric dose to 0.85 (95% CI, 0.76-0.95) at 2% dose using 2D and 3D images together. At 25% and 10% dose, 95% CI of the difference in figures of merit from routine dose included 0, suggesting similar or noninferior performance. CONCLUSIONS: For pediatric head CT for evaluation of craniosynostosis, dose reductions of 75%-90% were possible without compromising observer performance.

MPB64 mycobacterial antigen: a new skin-test reagent through patch method for rapid diagnosis of active tuberculosis.

SETTING: A collaborative study between the Japan BCG Laboratory, Tokyo, Japan, and the Infectious Disease Section, Philippine General Hospital, Manila, the Philippines. Tuberculosis patients from four clinics in the vicinity of Manila, Our Lady of Grace Parish, Sto. Niño de Tondo Parish, the Canossa Health and Social Center, and the Health Care Development Center, were examined. OBJECTIVE: To develop a new, simple and rapid diagnostic method for active tuberculosis. Subjects were tested for skin reaction to a special antigen, MPB64, by the patch test method instead of intradermal injection of purified protein derivative (PPD). DESIGN: Fifty-three active tuberculosis patients and 43 healthy PPD-positive controls were tested to determine whether or not the reaction to MPB64 was positive only in active tuberculosis patients. RESULTS: Fifty-two of the 53 active tuberculosis patients showed a positive reaction to MPB64, while none of the 43 PPD-positive controls did. The specificity of MPB64 to active tuberculosis was 100%, and the sensitivity was 98.1%. The efficacy of the test was 98.9%. CONCLUSION: The patch test with MPB64 is a promising method for the diagnosis of active tuberculosis, distinguishing tuberculous patients from those who are infected but have not developed the disease, and also from BCG-vaccinated individuals. This new skin test is a subject for further evaluation and it is important to compare the results with PPD Mantoux.

Nature of drug resistance and predictors of multidrug-resistant tuberculosis among patients seen at the Philippine General Hospital, Manila, Philippines.

SETTING: This study was conducted at the University of the Philippines--Philippine General Hospital (UP-PGH), Manila, Philippines. OBJECTIVES: To determine the nature of drug resistance among patients with pulmonary tuberculosis (PTB), and to establish clinical predictors of drug-resistant tuberculosis. DESIGN: Descriptive, prospective study. METHODS: Patients with positive culture for Mycobacterium tuberculosis were interviewed regarding past history of anti-tuberculosis treatment, BCG vaccination, chest X-ray and family contact. M. tuberculosis isolates from 299 patients were tested for susceptibility to rifampicin, isoniazid (INH), ethambutol and streptomycin using the submerged disc proportion method. Pyrazinamide (PZA) susceptibility test was done with standard laboratory powder in 7H10 media. RESULTS: Of the 299 M. tuberculosis isolates, 17% were fully susceptible to the 5 primary drugs and 54% were resistant to 2 or more drugs (multidrug resistant TB [MDR-TB]). Initial drug resistance rate was high with ethambutol (39%) and INH (17%). Previous history of anti-tuberculosis treatment was significantly associated with MDR-TB (Odds Ratio [OR] 2.44, 95% confidence interval). Incomplete anti-TB treatment taken for longer than 3 months increased the likelihood of MDR-TB (OR 4.6, P < 0.0001). CONCLUSION: The high rate of MDR-TB was associated with previous anti-tuberculosis treatment. The chance of developing MDR-TB was significantly increased when inadequate prior treatment was given for more than 3 months.