Evaluation of serial QuantiFERON-TB Gold in tube test results and tuberculosis infection status in patients with psoriasis receiving anti-IL-17 treatment (secukinumab and ixekizumab): Real-world data from a tuberculosis-endemic country.

BACKGROUND: In comparison with TNF-α inhibitors, anti-IL-17A agents are considered to have a lower risk of active tuberculosis (TB) or latent TB infection (LTBI) reactivation. METHODS: In this study, we aimed to evaluate the TB infection status and serial QuantiFERON-TB-Gold in tube test (QFT) results of psoriasis patients using IL-17 inhibitors (secukinumab [SEC] and ixekizumab [IXE]) in a real-world setting from a tuberculosis-endemic country. Patients who used an anti-IL-17 agent for at least 3 months in our follow-up were included in the study. Patients' clinical and demographic features, baseline QFT results and latest QFT results (if any), and TB infection status were noted from the past medical records. RESULTS: A total of 717 patients, of whom 333 (46.4%) were female, were included in the study. The cumulative exposure time to an anti-IL-17 agent was 14,147 patient-months, 9743 patient-months for SEC and 4404 patient-months for IXE. Also, 459 (SEC = 305/IXE = 154) patients used an anti-IL-17 agent for ≥ 12 months. Of these, 125 had positive baseline QFT results. In all, 334 had negative baseline QFT results. The latest QFT result of 309 was also negative (persistent seronegative group). During follow-up, the QFT results of 10 patients changed from negative to positive (positive seroconversion group). Seven of them were using SEC and three were using IXE, respectively. No case of active TB infection was detected. CONCLUSION: In our study, the positive seroconversion rate of 10/334 seems high, but this did not translate to active disease. However, closer monitoring may be required, especially in patients with advanced age, the presence of PsA, long disease duration and long anti-IL-17 treatment duration.

An exploratory deep learning approach to investigate tuberculosis pathogenesis in nonhuman primate model: Combining automated radiological analysis with clinical and biomarkers data.

BACKGROUND: Tuberculosis (TB) kills approximately 1.6 million people yearly despite the fact anti-TB drugs are generally curative. Therefore, TB-case detection and monitoring of therapy, need a comprehensive approach. Automated radiological analysis, combined with clinical, microbiological, and immunological data, by machine learning (ML), can help achieve it. METHODS: Six rhesus macaques were experimentally inoculated with pathogenic Mycobacterium tuberculosis in the lung. Data, including Computed Tomography (CT), were collected at 0, 2, 4, 8, 12, 16, and 20 weeks. RESULTS: Our ML-based CT analysis (TB-Net) efficiently and accurately analyzed disease progression, performing better than standard deep learning model (LLM OpenAI's CLIP Vi4). TB-Net based results were more consistent than, and confirmed independently by, blinded manual disease scoring by two radiologists and exhibited strong correlations with blood biomarkers, TB-lesion volumes, and disease-signs during disease pathogenesis. CONCLUSION: The proposed approach is valuable in early disease detection, monitoring efficacy of therapy, and clinical decision making.

Three-Dimensional Rotary Culture to Model Mycobacterial Biofilms in Low-Shear Detergent-Free Liquid Suspension.

In vitro biofilm models have allowed researchers to investigate the role biofilms play in the pathogenesis, virulence, and antimicrobial drug susceptibility of a wide range of bacterial pathogens. Rotary cell culture systems create three-dimensional cellular structures, primarily applied to eukaryotic organoids, that better capture characteristics of the cells in vivo. Here, we describe how to apply a low-shear, detergent-free rotary cell culture system to generate biofilms of Mycobacterium bovis BCG. The three-dimensional biofilm model forms mycobacterial cell aggregates in suspension as surface-detached biomass, without severe nutrient starvation or environmental stress, that can be harvested for downstream experiments. Mycobacterium bovis BCG derived from cell clusters display antimicrobial drug tolerance, presence of an extracellular matrix, and evidence of cell wall remodeling, all features of biofilm-associated bacteria that may be relevant to the treatment of tuberculosis.

A Microtiter Plate Assay at Acidic pH to Identify Potentiators that Enhance Pyrazinamide Activity Against Mycobacterium tuberculosis.

Pyrazinamide (PZA) is a key component of chemotherapy for the treatment of drug-susceptible tuberculosis (TB) and is likely to continue to be included in new drug combinations. Potentiation of PZA could be used to reduce the emergence of resistance, shorten treatment times, and lead to a reduction in the quantity of PZA consumed by patients, thereby reducing the toxic effects. Acidified medium is required for the activity of PZA against Mycobacterium tuberculosis. In vitro assessments of pyrazinamide activity are often avoided because of the lack of standardization, which has led to a lack of effective in vitro tools for assessing and/or enhancing PZA activity.We have developed and optimized a novel, robust, and reproducible, microtiter plate assay, that centers around acidity levels that are low enough for PZA activity. The assay can be applied to the evaluation of novel compounds for the identification of potentiators that enhance PZA activity. In this assay, potentiation of PZA is demonstrated to be statistically significant with the addition of rifampicin (RIF), which can, therefore, be used as a positive control. Conversely, norfloxacin demonstrates no potentiating activity with PZA and can be used as a negative control. The method, and the associated considerations, described here, can be adapted in the search for potentiators of other antimicrobials.

Monitoring Live Mycobacteria in Real-Time Using a Microfluidic Acoustic-Raman Platform.

Tuberculosis (TB) is the most common cause of death from an infectious disease. Although treatment has been available for more than 70 years, it still takes too long and many patients default risking relapse and the emergence of resistance. It is known that lipid-rich, phenotypically antibiotic-tolerant, bacteria are more resistant to antibiotics and may be responsible for relapse necessitating extended therapy. Using a microfluidic system that acoustically traps live mycobacteria, M. smegmatis, a model organism for M. tuberculosis we can perform optical analysis in the form of wavelength-modulated Raman spectroscopy (WMRS) on the trapped organisms. This system can allow observations of the mycobacteria for up to 8 h. By adding antibiotics, it is possible to study the effect of antibiotics in real-time by comparing the Raman fingerprints in comparison to the unstressed condition. This microfluidic platform may be used to study any microorganism and to dynamically monitor its response to many conditions including antibiotic stress, and changes in the growth media. This opens the possibility of understanding better the stimuli that trigger the lipid-rich downregulated and phenotypically antibiotic-resistant cell state.

Quantifying Viable M. tuberculosis Safely Obviating the Need for High Containment Facilities.

Mycobacterium tuberculosis is an infectious pathogen that requires biosafety level-3 laboratory for handling. The risk of transmission is high to laboratory staff, and to manage the organism safely, it is necessary to construct high containment laboratory facilities at great expense. This limits the application of tuberculosis diagnostics to areas where there is insufficient capital to invest in laboratory infrastructure. In this method, we describe a process of inactivating sputum samples by either heat or guanidine thiocyanate (GTC) that renders them safe without affecting the quantification of viable bacteria. This method eliminates the need for level 3 containment laboratory for the tuberculosis molecular bacterial load assay (TB-MBLA) and is applicable in low- and middle-income countries.

Improved Diagnosis and Treatment Monitoring of Tuberculosis Using Stool and the Tuberculosis Bacterial Load Assay (TB-MBLA).

The diagnosis and monitoring of tuberculosis treatment is difficult as many patients are unable to produce sputum. This means that many patients are treated on the basis of clinical findings and consequently some will be exposed to anti-tuberculosis drugs unnecessarily. Moreover, for those appropriately on treatment and unable to produce a sputum sample, it will be impossible to monitor the response to treatment. We have shown that stool is a potential alternative sample type for diagnosis of tuberculosis. Currently, available protocols like the Xpert MTB/RIF use DNA as a target to detect Mycobacterium tuberculosis in stool but DNA survives long after the organism is dead so it is not certain whether a positive test is from an old or a partially treated infection. The TB MBLA only detects live organisms and thus, can be used to follow the response to treatment. In this chapter, we describe a protocol for TB-MBLA, an RNA-based assay, and apply it to quantify TB bacteria in stool.

Use of Whole Genome Sequencing for Mycobacterium tuberculosis Complex Antimicrobial Susceptibility Testing: From Sequence Data to Resistance Profiles.

Whole genome sequencing of Mycobacterium tuberculosis complex (MTBC) isolates has been shown to provide accurate predictions for resistance and susceptibility for many first- and second-line anti-tuberculosis drugs. However, bioinformatic pipelines and mutation catalogs to predict antimicrobial resistances in MTBC isolates are often customized and detailed protocols are difficult to access. Here, we provide a step-by-step workflow for the processing and interpretation of short-read sequencing data and give an overview of available analysis pipelines.

Use of Whole Genome Sequencing for Mycobacterium tuberculosis Complex Antimicrobial Susceptibility Testing.

Whole genome sequencing (WGS) is becoming an important diagnostic tool for antimicrobial susceptibility testing of Mycobacterium tuberculosis complex (MTBC) isolates in many countries. WGS protocols usually start with the preparation of a DNA-library: the critical first step in the process. A DNA-library represents the genomic content of a DNA sample and consists of unique short DNA fragments. Although available DNA-library protocols come with manufacturer instructions, details of the entire process, including quality controls, instrument parameters, and run evaluations, often need to be developed and customized by each laboratory to implement WGS technology effectively. Here, we provide a detailed workflow for a DNA-library preparation based on an adapted Illumina protocol optimized for the reduction of reagent costs.

Regulatory role of Mycobacterium tuberculosis MtrA on dormancy/resuscitation revealed by a novel target gene-mining strategy.

Introduction: The unique dormancy of Mycobacterium tuberculosis plays a significant role in the major clinical treatment challenge of tuberculosis, such as its long treatment cycle, antibiotic resistance, immune escape, and high latent infection rate. Methods: To determine the function of MtrA, the only essential response regulator, one strategy was developed to establish its regulatory network according to high-quality genome-wide binding sites. Results and discussion: The complex modulation mechanisms were implied by the strong bias distribution of MtrA binding sites in the noncoding regions, and 32.7% of the binding sites were located inside the target genes. The functions of 288 potential MtrA target genes predicted according to 294 confirmed binding sites were highly diverse, and DNA replication and damage repair, lipid metabolism, cell wall component biosynthesis, cell wall assembly, and cell division were the predominant pathways. Among the 53 pathways shared between dormancy/resuscitation and persistence, which accounted for 81.5% and 93.0% of the total number of pathways, respectively, MtrA regulatory genes were identified not only in 73.6% of their mutual pathways, but also in 75.4% of the pathways related to dormancy/resuscitation and persistence respectively. These results suggested the pivotal roles of MtrA in regulating dormancy/resuscitation and the apparent relationship between dormancy/resuscitation and persistence. Furthermore, the finding that 32.6% of the MtrA regulons were essential in vivo and/or in vitro for M. tuberculosis provided new insight into its indispensability. The findings mentioned above indicated that MtrA is a novel promising therapeutic target for tuberculosis treatment since the crucial function of MtrA may be a point of weakness for M. tuberculosis.

Multiple intracranial tuberculomas in an elderly patient: A central nervous system tuberculosis case in the emergency department.

A 67-year-old male presented to the emergency department with a 7-day history of fever, malaise, myalgia, headache, and a seizure episode. Physical examination showed stable vital signs but a fever. Laboratory tests indicated leukocytosis, anemia, thrombocytosis, and elevated inflammatory markers. Imaging revealed multiple intracranial lesions, and cerebrospinal fluid analysis confirmed the presence of acid-fast bacilli. The patient responded well to anti-tuberculosis therapy, showing significant clinical improvement within 8 weeks.

Laparoscopic Retrograde Nephrectomy as a Troubleshooting Technique to Prevent Open Conversion: The Technique Description With a Review of 40 Cases.

Introduction Laparoscopic nephrectomies are safe, with low complication rates in skilled hands. However, traditional approaches may be unsuitable for conditions such as post-renal abscesses, long-standing urinomas, non-functioning kidneys post-pyeloplasty, pyelolithotomies, post-partial nephrectomy recurrences, tuberculous kidneys, pyelonephritis, and redo-renal surgeries. This study describes a modified retrograde nephrectomy technique and its outcomes in 40 cases. Methods We reviewed 40 cases where the retrograde nephrectomy technique was used. Surgeons opted for this method based on intraoperative findings and initial difficulties in accessing the lower pole area. Results Traditional dissection was challenging due to adhesions in the lower pole. The retrograde technique, starting from the renal hilum, allowed early ligation of renal arteries and veins, reducing bleeding risks and facilitating safer caudal dissection. Conclusions The retrograde nephrectomy technique offers a safer and more efficient alternative for complex nephrectomies. Early vascular control minimizes hemorrhage risk, making it a valuable method in challenging renal surgeries.

Polymerase Chain Reaction (PCR) Profiling of Extensively Drug-Resistant (XDR) Pathogenic Bacteria in Pulmonary Tuberculosis Patients.

Introduction Pulmonary tuberculosis (TB) remains a global health concern, exacerbated by the emergence of extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis. This study employs advanced molecular techniques, specifically polymerase chain reaction (PCR) profiling, to comprehensively characterize the genetic landscape of XDR pathogenic bacteria in patients diagnosed with pulmonary TB. The objective of the study is to elucidate the genes that are associated with drug resistance in pulmonary TB strains through the application of PCR and analyze specific genetic loci that contribute to the development of resistance against multiple drugs. Materials and methods A total of 116 clinical samples suspected of TB were collected from the tertiary healthcare setting of Saveetha Medical College and Hospitals for the identification of MTB, which includes sputum (n = 35), nasal swabs (n = 17), blood (n = 44), and bronchoalveolar lavage (BAL) (n = 20). The collected specimens were processed and subjected to DNA extraction. As per the protocol, reconstitution of the DNA pellet was carried out. The reconstituted DNA was stored at -20 °C for the PCR assay. From the obtained positive sample specimens, XDR pulmonary TB specimens were focused on the targeted genes, specifically the rpoB gene for rifampicin resistance, inhA, and katG gene for thepromoter region for isoniazid resistance. Results Out of a total of 116 samples obtained, 53 tested positive for pulmonary TB, indicative of a mycobacterial infection. Among these positive cases, 43 patients underwent treatment at a tertiary healthcare facility. Subsequently, a PCR assay was performed with the extracted DNA for the target genes rpoB, inhA, and katG. Specifically, 22 sputum samples exhibited gene expression for rpoB, inhA, and katG, while nine nasal swabs showed expression of the rpoB and inhA genes. Additionally, rpoB gene expression was detected in seven blood specimens, and both rpoB and inhA genes were expressed in five BAL samples. Conclusion The swift diagnosis and efficient treatment of XDR-TB can be facilitated by employing advanced and rapid molecular tests and oral medication regimens. Utilizing both newly developed and repurposed anti-TB drugs like pretomanid, bedaquiline, linezolid, and ethionamide. Adhering to these current recommendations holds promise for managing XDR-TB effectively. Nevertheless, it is significant to conduct well-designed clinical trials and studies to further evaluate the efficacy of new agents and shorter treatment regimens, thus ensuring continuous improvement in the management of this challenging condition.

Tuberculosis of the Cervical Vertebrae With Retropharyngeal and Parapharyngeal Abscesses Due to Staphylococcus aureus and Mycobacterium tuberculosis in an Adult: A Report of a Rare Case.

Tuberculosis is a disease with presentations both in the lungs and at other extrapulmonary sites. While pulmonary tuberculosis constitutes a significant proportion of total tuberculosis cases, extrapulmonary cases with infections at rare sites are also documented. Herein, an exceedingly rare case of tuberculosis of the cervical vertebrae with retropharyngeal and parapharyngeal abscesses due to Staphylococcus aureus and Mycobacterium tuberculosis in a young Indian male is presented. The rarity of the locations of the lesions with coinfections with two bacteria made the diagnosis challenging. Besides, the potential for a retropharyngeal abscess to compress the airway is an emergency situation. However, the ultimate diagnosis was achieved with the help of a radiograph of the neck, contrast-enhanced computed tomography of the neck, fine-needle aspiration cytology, and a cartridge-based nucleic acid amplification test. He was initiated on appropriate antibiotics and antituberculous chemotherapy per his weight.

Identification of host immune-related biomarkers in active tuberculosis: A comprehensive analysis of differentially expressed genes.

Tuberculosis (TB) is a serious public health issue in India. Numerous molecular mechanisms and immunological responses play significant roles in the pathogenesis of tuberculosis. This study aimed to identify host immune-related biomarkers that are significantly differentially expressed in active TB and that play a vital role in disease progression. The methodology employed in this study included data collection, pre-processing, analysis, and interpretation of the results. Six microarray datasets were used to identify differentially expressed genes (DEGs), and only the common DEGs were used for further downstream analysis, such as hub gene identification, gene ontology, pathway enrichment analysis, and drug-gene interaction analysis. The study identified 1728 DEGs, including 906 upregulated and 822 downregulated genes. Five hub genes were identified that were: STAT1, GBP5, GBP1, FCGR1A, and BATF2. Gene ontology and pathway enrichment revealed that most of the genes were involved in interferon-gamma signaling. In addition, through drug-gene interactions, known drugs have been identified for STAT1, FCGR1A and GBP1. The findings of this study may contribute to early detection and treatment of active TB.

Retrospective analysis of the clinical utility of multi-cytokine profiles in smear-negative pulmonary tuberculosis.

OBJECTIVES: To evaluate cytokine profiles and interferon-gamma release assay (IGRA) for their diagnostic capabilities in the differentiation of tuberculosis (TB) from non-TB conditions, as well as smear-negative pulmonary tuberculosis (SNPT) from smear-positive pulmonary tuberculosis (SPPT). METHODS: A total of 125 participants were included, 77 of whom had TB and 48 who didn't, and demographic, clinical, and laboratory data were collected, including cytokine levels and IGRA results. The TB patients were further divided into 2 subgroups: SNPT (n=42) and SPPT (n=35). RESULTS: Compared to non-TB, the TB group had lower BMI, higher WBC, neutrophils, monocytes, ESR and CRP (p<0.05). TB patients showed higher IL-2, IL-6, IFN-γ, IL-8 (p<0.001) and higher IGRA positivity (88.3% versus [vs.] 29.2%, p<0.001). Between SNPT and SPPT, moderate effect sizes were observed for IFN-α, IL-2, IL-10, IL-8 (Cohen's d 0.59-0.76), with lower IGRA positivity in SNPT (81.0% vs. 97.1%, p=0.015). ROC analysis indicated IFN-α, IL-2, IL-10, IL-8 had moderate accuracy for SNPT diagnosis (AUCs 0.668-0.734), and combining these improved accuracy (AUC 0.759, 80% sensitivity, 64.2% specificity). CONCLUSION: A multi-biomarker approach combining these cytokines demonstrates enhanced diagnostic accuracy for tuberculosis.

Endoscopic decompression of severe post-tuberculosis kyphosis related ossification of the ligamentum flavum: case report and literature review.

PURPOSE: Spinal tuberculosis, if not promptly treated, can lead to kyphotic deformity, causing persistent neurological abnormalities and discomfort. Spinal cord compression can occur due to ossification of the ligamentum flavum (OLF) at the apex of kyphosis. Traditional surgical interventions, including osteotomy and fixation, pose challenges and risks. We present a case of thoracic myelopathy in a patient with post-tuberculosis kyphosis, successfully treated with biportal endoscopic spinal surgery (BESS). METHOD: A 73-year-old female with a history of untreated kyphosis presented with walking difficulties and lower limb pain. Imaging revealed a kyphotic deformity of 120° and OLF-induced cord compression at T8-9. UBE was performed under spinal anesthesia. Using the BESS technique, OLF was successfully removed with minimal damage to the stabilizing structures. RESULTS: The patient exhibited neurological improvement after surgery, walking on the first day without gait instability. Follow-up at 1 year showed no kyphosis progression or recurrence of symptoms. BESS successfully resolved the cord compression lesion with minimal blood loss and damage. CONCLUSION: In spinal tuberculosis-related OLF, conventional open surgery poses challenges. BESS emerges as an excellent alternative, providing effective decompression with reduced instrumentation needs, minimal blood loss, and preservation of surrounding structures. Careful patient selection and surgical planning are crucial for optimal outcomes in endoscopic procedures.

Sex disparities of the effect of the COVID-19 pandemic on mortality among patients living with tuberculosis in the United States.

Background: We aimed to determine the trend of TB-related deaths during the COVID-19 pandemic. Methods: TB-related mortality data of decedents aged ≥25 years from 2006 to 2021 were analyzed. Excess deaths were estimated by determining the difference between observed and projected mortality rates during the pandemic. Results: A total of 18,628 TB-related deaths were documented from 2006 to 2021. TB-related age-standardized mortality rates (ASMRs) were 0.51 in 2020 and 0.52 in 2021, corresponding to an excess mortality of 10.22 and 9.19%, respectively. Female patients with TB demonstrated a higher relative increase in mortality (26.33 vs. 2.17% in 2020; 21.48 vs. 3.23% in 2021) when compared to male. Female aged 45-64 years old showed a surge in mortality, with an annual percent change (APC) of -2.2% pre-pandemic to 22.8% (95% CI: -1.7 to 68.7%) during the pandemic, corresponding to excess mortalities of 62.165 and 99.16% in 2020 and 2021, respectively; these excess mortality rates were higher than those observed in the overall female population ages 45-64 years in 2020 (17.53%) and 2021 (33.79%). Conclusion: The steady decline in TB-related mortality in the United States has been reversed by COVID-19. Female with TB were disproportionately affected by the pandemic.

The effect of an intervention to promote isoniazid preventive therapy on leadership and management abilities.

BACKGROUND: Across sub-Saharan Africa, mid-level healthcare managers oversee implementation of national guidelines. It remains unclear whether leadership and management training can improve population health outcomes. METHODS: We sought to evaluate leadership/management skills among district-level health managers in Uganda participating in the SEARCH-IPT randomised trial to promote isoniazid preventive therapy (IPT) for persons with HIV (PWH). The intervention, which led to higher IPT rates, included annual leadership/management training of managers. We conducted a cross-sectional survey assessing leadership/management skills among managers at trial completion. The survey evaluated self-reported use of leadership/management tools and general leadership/management. We conducted a survey among a sample of providers to understand the intervention's impact. Targeted minimum loss-based estimation (TMLE) was used to compare responses between trial arms. RESULTS: Of 163 managers participating in the SEARCH-IPT trial, 119 (73%) completed the survey. Intervention managers reported more frequent use of leadership/management tools taught in the intervention curriculum than control managers (+3.64, 95% CI 1.98-5.30, P < 0.001). There were no significant differences in self-reported leadership skills in the intervention as compared to the control group. Among providers, the average reported quality of guidance and supervision was significantly higher in intervention vs control districts (+1.08, 95% CI 0.63-1.53, P = 0.001). CONCLUSIONS: A leadership and management training intervention increased the use of leadership/management tools among mid-level managers and resulted in higher perceived quality of supervision among providers in intervention vs control districts in Uganda. These findings suggest improved leadership/management among managers contributed to increased IPT use among PWH in the intervention districts of the SEARCH-IPT trial.

CONTEXTE: Dans toute l'Afrique subsaharienne, les gestionnaires de soins de santé de niveau intermédiaire supervisent la mise en œuvre des directives nationales. Il n'est toujours pas clair si la formation en leadership et en gestion peut améliorer les résultats en matière de santé de la population. MÉTHODES: Nous avons cherché à évaluer les compétences en leadership et en gestion des responsables de la santé au niveau des districts en Ouganda participant à l'essai randomisé SEARCH-IPT visant à promouvoir le traitement préventif à l'isoniazide (TPI) pour les personnes vivant avec le VIH (PWH, pour l'anglais « people living with HIV ¼). L'intervention, qui a permis d'augmenter les taux de TPI, comprenait une formation annuelle en leadership et en gestion des gestionnaires. Nous avons mené une enquête transversale pour évaluer les compétences en leadership et en gestion des gestionnaires à la fin de l'essai. L'enquête a évalué l'utilisation autodéclarée d'outils de leadership et de gestion et de leadership et de gestion en général. Nous avons mené une enquête auprès d'un échantillon de prestataires pour comprendre l'impact de l'intervention. L'estimation ciblée basée sur les pertes minimales (TMLE, « Targeted minimum loss-based estimation ¼) a été utilisée pour comparer les réponses entre les groupes de l'essai. RÉSULTATS: Sur les 163 gestionnaires qui ont participé à l'essai SEARCH-IPT, 119 (73%) ont répondu au sondage. Les gestionnaires d'intervention ont déclaré utiliser plus fréquemment les outils de leadership/gestion enseignés dans le programme d'intervention que les gestionnaires de contrôle (+3,64 ; IC à 95% 1,98­5,30 ; P < 0,001). Il n'y avait pas de différences significatives dans les compétences de leadership autodéclarées dans l'intervention par rapport au groupe témoin. Parmi les prestataires, la qualité moyenne déclarée de l'orientation et de la supervision était significativement plus élevée dans les districts d'intervention que dans les districts témoins (+1,08 ; IC à 95% 0,63­1,53 ; P = 0,001). CONCLUSIONS: Une intervention de formation au leadership et à la gestion a permis d'accroître l'utilisation d'outils de leadership et de gestion parmi les cadres intermédiaires et d'améliorer la perception de la qualité de la supervision parmi les prestataires dans les districts d'intervention par rapport aux districts de contrôle en Ouganda. Ces résultats suggèrent que l'amélioration du leadership et de la gestion chez les gestionnaires a contribué à l'augmentation de l'utilisation du TPI chez les personnes handicapées dans les districts d'intervention de l'essai SEARCH-IPT.