Introduction: Disseminated histoplasmosis is a rare but important cause of adrenal insufficiency (AI), particularly in tuberculosis (TB)-endemic regions, where it may mimic granulomatous diseases. Adrenal involvement occurs in up to 80% of disseminated cases, although overt AI is less common. Reported cases described bilateral adrenal masses mimicking malignancy or TB, even in immunocompetent individuals. Addisonian crisis may be the initial manifestation, especially when the diagnosis is delayed. In TB-endemic settings, fungal infections are often overlooked, leading to delayed diagnosis and inappropriate therapy. Case: We reported a case of a 68-year-old male with underlying diabetes mellitus who presented with fever, cough, dysphagia, and weight loss for 1 month. He was empirically treated as smear-negative disseminated TB. On day 2 of therapy, he developed hypotension (80/50 mmHg), hypoglycemia (3.9 mmol/L), hyponatremia (Na 129 mmol/L), and hyperkalemia (K 5.1 mmol/L), suggestive of adrenal crisis, and was started on intravenous hydrocortisone. Serum cortisol prior to treatment was 61 nmol/L. Computed tomography (CT) imaging revealed bilateral lipid-poor adrenal lesions (right: 3.6 × 2.2 × 4.9 cm, Hounsfield Unit (HU) 36 and absolute washout 33%; left: 3.5 × 2.4 × 5.4 cm; HU 35 and absolute washout 17%), raising suspicion of infectious or malignant etiologies. Endoscopic ultrasound-guided biopsy demonstrated necrotizing granulomatous inflammation with budding fungal yeasts on Pituitary Apoplexy Score and GMS staining, consistent with Histoplasma capsulatum. TB and malignancy were excluded. He received amphotericin B for 14 days, followed by oral itraconazole for 1 year, and oral hydrocortisone replacement. At 1-year follow-up, adrenal lesions remained stable on CT images, and he continued to require hydrocortisone replacement. Conclusion This case highlights the importance of considering disseminated histoplasmosis as a differential diagnosis of bilateral adrenal masses with AI, especially with poor response to anti-TB therapy. Early tissue diagnosis is essential, as imaging findings are non-specific. Prompt recognition is critical to prevent life-threatening adrenal crisis and improve clinical outcomes.
Histoplasmosis ; Tuberculosis

Introduction: Adrenal tuberculosis (TB) is a rare but important cause of adrenal insufficiency in TB-endemic regions, usually secondary to pulmonary or extrapulmonary disease, with primary involvement being uncommon. It typically affects both glands via hematogenous or lymphatic spread and presents late with nonspecific features after significant adrenal destruction, making diagnosis challenging. Diagnosis is more straightforward in the presence of extraadrenal TB, where imaging may obviate the need for biopsy, but remains difficult in isolated adrenal involvement. Case: We report a 69-year-old Malay male with diabetes mellitus, hypertension, and hyperlipidemia who presented with a 2-week history of chronic cough and 4 months of constitutional symptoms, including weight loss and anorexia. Initial TB workup in September 2025 was negative. He was subsequently admitted twice in October 2025 for pneumonia, with persistent upper lobe consolidation on chest radiography despite antibiotics. Contrast-enhanced computed tomography thorax, abdomen, and pelvis revealed bilateral mildly enhancing hypodense adrenal lesions (right 3.7 × 3.0 cm, left 2.5 × 2.6 cm), suggestive of adenoma, hyperplasia, or lymphoma. Bronchoscopy detected Mycobacterium tuberculosis via GeneXpert BAL, with no malignant cells on cytology. Adrenal biopsy was non-diagnostic. Biochemical evaluation showed low morning cortisol with elevated adrenocorticotropic hormone and findings consistent with adrenal insufficiency. The patient was treated as smear-negative pulmonary TB with adrenal involvement and initiated on anti-TB therapy, currently in the maintenance phase. Hydrocortisone replacement 10 mg twice daily was also initiated. Conclusion This case highlights the diagnostic challenge of adrenal TB, particularly when tissue sampling is inconclusive. In TB-endemic settings, a presumptive diagnosis based on clinical, radiological, and microbiological evidence is often necessary. Early empiric anti-TB therapy is essential to prevent adrenal crisis and preserve endocrine function.
Tuberculosis

Introduction: Diabetes mellitus (DM) is a significant comorbidity associated with adverse tuberculosis (TB) treatment outcomes and remains an ongoing clinical challenge. Chronic hyperglycemia impairs host immune responses, particularly macrophage function, leading to delayed bacillary clearance. This contributes to poorer outcomes, including delayed sputum conversion, prolonged treatment duration, relapse, and increased mortality. Poor glycemic control is a key modifiable factor influencing these outcomes. This study aimed to evaluate the impact of glycemic control at diagnosis on TB treatment outcomes in a Malaysian cohort. Methodology: A retrospective cross-sectional audit was conducted using the TB clinic registry at Hospital Sungai Buloh from 2022 to 2025. Adult patients (≥18 years) with confirmed TB (any form) and DM (Type 1 or Type 2) with complete records were included. Of 241 patients screened, 131 were included after exclusions due to incomplete records (29.9%), transfer (29.9%), loss to follow-up (19.9%), and drug-resistant TB (2.9%). Data collected included demographics, hemoglobin A1c (HbA1c) at diagnosis, sputum conversion duration, treatment duration, type of DM therapy, and clinical outcomes. Results: The cohort had a mean age of 53 years, with 97% having Type 2 DM. Mean HbA1c at diagnosis was 10.5%. Poorer glycemic control was associated with delayed sputum conversion. Patients who achieved sputum conversion by 8 weeks had an average HbA1c of 9.6%, compared to 11.8% in those with delayed conversion. Longer treatment duration was associated with higher HbA1c (mean 10.5, 8.6, and 11.8% for 6-, 12-, and 18-month regimens, respectively). Relapse analysis demonstrated a trend towards higher HbA1c with increasing relapse episodes (11.2, 13.75, and 14.5% for one, two, and three relapses, respectively). Overall mortality was 17% (22/131), with markedly higher mean HbA1c in deceased patients compared to survivors (16.0% vs 10.5%). Conclusion Poor glycemic control at TB diagnosis is associated with delayed sputum conversion, prolonged treatment duration, and increased mortality. These findings are consistent with regional evidence, including a South Asian systematic review (Gautam et al., 2021), demonstrating higher mortality and treatment failure in patients with TB and DM. Early and aggressive optimization of glycemic control, alongside standard anti-TB therapy, is essential to improve outcomes.
Humans ; Glycemic Control ; Retrospective Studies ; Diabetes Mellitus ; Treatment Outcome ; Tuberculosis

Introduction: Electrolyte imbalance is common in central nervous system infections. Arginine vasopressin deficiency (AVP-D), Cerebral Salt Wasting (CSW), and Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) are important etiologies that can cause opposing extremes of serum sodium, posing diagnostic and therapeutic challenges. We report a rare case of transient central AVP-D followed by CSW secondary to tuberculous meningitis (TBM). Case: An 18-year-old female presented with a 1-month history of fever, reduced responsiveness, and visual hallucinations. Her Glasgow Coma Scale was E4V1M4 with neck stiffness and upper motor neuron signs. Initial investigations revealed severe hyponatremia (119 mmol/L) and communicating hydrocephalus with third ventricle ballooning on brain imaging. Coupled with a positive tuberculosis contact, anti-tuberculous therapy was initiated for probable TBM alongside 3% saline correction prior to insertion of external ventricular drain (EVD). Her condition deteriorated on day 5, requiring intubation for aspiration pneumonia. Repeated imaging showed worsening hydrocephalus, necessitating EVD revision. She subsequently developed polyuria (urine output [UO] 150–300 mLs/hour), with biochemical findings consistent with AVP-D (serum sodium 154 mmol/L; urine osmolality 96 mOsm/kg; urine sodium <20 mmol/L). Intravenous desmopressin 1 mcg was administered, and UO reduced to 30 mLs/hour. However, polyuria recurred on Day 9, accompanied by tachycardia, hypotension, and a rapid decline in serum sodium to 120 mmol/L. Diagnosis of CSW was established (urine sodium 204 mmol/L; urine osmolality 470 mOsm/kg). Oral fludrocortisone was initiated and titrated to 0.4 mg daily to maintain serum sodium >130 mmol/L. Due to persistent hydrocephalus, right ventriculoperitoneal shunt was inserted on Day 22, after which her UO gradually decreased, allowing tapering of fludrocortisone. She remains on fludrocortisone 0.1 mg daily with ongoing rehabilitation. Conclusion TBM can be complicated by SIADH, AVP-D, or CSW. Concurrent AVP-D and CSW have not been reported. This case highlights the dynamic electrolyte disturbances in TBM which may lead to diagnostic confusion and therapeutic error. Early recognition and tailored therapy, alongside definitive management to reduce intracranial pressure, are essential for optimal outcomes.
Hypernatremia ; Hyponatremia ; Tuberculosis, Meningeal

OBJECTIVES

 

METHODS

We included all SLE cases reported between January 2021 and December 2022 based on our Rheumatology Section census in this retrospective chart review. We evaluated the changes in the prednisone dosage and the lupus disease activity before, during and after completion of tuberculosis (TB) treatment. The characteristics of the patients were also described.

RESULTS

All the subjects in the study were females with a mean age of 35.85 years. The pulmonary site (50 %) is the most common area of involvement in tuberculosis infection. Prior to anti-TB treatment, the mean MEX-SLEDAI score was 5.45 (SD ± 4.20) within 1 year prior to the TB diagnosis with prednisone dosage mean of 14 mg (SD ± 17.0). Three months after anti-tuberculosis medication initiation, the prednisone dosages and the MEX-SLEDAI increased however, the changes were not statistically significant. Within 1 month of completion of anti-TB treatment, there was decrease in the MEX-SLEDAI with mean of 3 (SD ± 3.68) and dosages of prednisone with mean of 4.38 mg (SD 3.13). The changes were statistically significant with p-values of

CONCLUSION

There were no significant changes in the MEX-SLEDAI and prednisone dosage within 3 months of starting antiTB medications. However, completion of treatment results to better SLE disease scores and lower prednisone requirements.

Human ; Female ; Adult: 25-44 Yrs Old ; Middle Aged: 45-64 Yrs Old ; Aged: 65-79 Yrs Old ; Tuberculosis ; Therapeutics ; Rheumatology ; Diagnosis ; Censuses ; Prednisone

BACKGROUND AND OBJECTIVE

The COVID-19 pandemic has adversely affected various healthcare services worldwide, including tuberculosis (TB) control programs. This paper examines the impact of the COVID-19 pandemic on TB case notification rate (CNR) and treatment success rate (TSR), and the challenges and interventions in TB-DOTS (directly observed treatment short-course) services in the Province of South Cotabato, SOCCSKSARGEN Region, Philippines. 

METHODS

An explanatory sequential mixed methods design was used to describe the experiences of South Cotabato in implementing TB-DOTS services during COVID-19 pandemic. Monthly data on CNR and TSR under TB-DOTS from March 2019 to February 2022 were retrieved from the Department of Health’s Integrated Tuberculosis Information System (ITIS) through records review. One-way analysis of variance (ANOVA) and Tukey’s test were used to analyze quantitative data. Focus group discussions (FGD) were conducted among four groups of program implementers (NTP coordinators, nurses, medical technologists, and barangay health workers) encompassing the challenges encountered in the implementation of TB-DOTS services as well as interventions done before and during the COVID-19 pandemic.

RESULTS

During the pre-COVID-19 period (March 2019-February 2020), a CNR of 334 per 100,000 population was reported in the province. There is a 35.19% decrease in TB CNR during COVID-19 Year 1 (March 2020-February 2021) at 216 per 100,000 population, followed by a 37.63% increase in Year 2 at 298 per 100,000 population. The mean TSR covering the pre-COVID period was 96% (SD = 0.01) while the mean TSR in COVID-19 Year 1 was 93% (SD = 0.02), significantly lower than that of the pre-pandemic period, followed by monthly TSR ranging from 91% to 98% (SD = 0.02), an increase in Year 2. From the FGDs, six pre-existing barriers were identified such as patients’ f inancial constraints, hard-to-reach areas, poor health seeking behavior, persistence of TB stigma, medicine and supply shortages, and inadequate health workforce were experienced before and during the COVID-19 pandemic. On the other hand, six emerging challenges brought by the COVID-19 pandemic were reallocation of services, movement restriction, additional protocols, reporting delays, and fears among patients and health workers. The decrease in CNR and TSR during COVID-19 Year 1 aligned with the emergence of new challenges in TB-DOTS services brought by the pandemic. These aggravated pre-existing barriers which further caused delays in the diagnosis and treatment of TB patients. Nine interventions done to address these challenges were also described, the most critical being health education, strengthening community-based services, use of telecommunications, resource pooling for essential medicines, adjusting medication dispensing, and coordination with local government units and policy enhancements.

CONCLUSION

TB-DOTS services in South Cotabato experienced various difficulties during the COVID-19 pandemic which led to initial declines in CNR and TSR. Addressing barriers and challenges were vital in ensuring the continuity of TB services and mitigating the impact of COVID-19 crisis on CNR and TSR. This study demonstrates the adaptability and resilience of South Cotabato's TB-DOTS services in response to COVID-19 challenges and highlights the need for strategies ensuring continuity of TB services and healthcare system resilience in light of Universal Health Care. Recommendations are outlined to improve current policies and practices as well as lay future directions for research on health service delivery and program implementation in relation to pandemics and other types of disasters.

Human ; Tuberculosis ; Covid-19 ; Pandemics ; Philippines

Bone tuberculosis is one of the main lesions of extrapulmonary tuberculosis, and the affected site shows local pain and limited movement, and the severe patients face a higher risk of teratogenicity and disability. Especially in the context of the increasing spread of multidrug-resistant tuberculosis, it is particularly urgent to seek innovative treatment options. In recent years, vitamin D plays an important role in the prevention and treatment of bone tuberculosis, and the mechanism of action has been continuously explored. At the same time, vitamin D receptor gene polymorphism has also been found to be closely related to the susceptibility and risk of bone tuberculosis. This article reviewed the relationship between vitamin D and its receptor gene polymorphisms and the susceptibility to bone tuberculosis. It was found that vitamin D deficiency increased the susceptibility to bone tuberculosis in both adults and children, and multiple genotypes of vitamin D receptor had an effect on the susceptibility to bone tuberculosis, especially FokⅠ genotype. It may also be one of the reasons for the increase in the number of bone tuberculosis. Through the study of the relationship between vitamin D and its receptor gene polymorphism and the susceptibility to bone tuberculosis, some factors inducing bone tuberculosis can be avoided, and related new drugs can be more targeted, such as vitamin D supplements, gene receptor related antagonists, etc. To provide more systematic and targeted strategies for the prevention and treatment of bone tuberculosis.
Humans ; Receptors, Calcitriol/genetics* ; Genetic Predisposition to Disease ; Polymorphism, Genetic ; Vitamin D/metabolism* ; Tuberculosis, Osteoarticular/metabolism*

Objective The prevalence of drug-resistant Mycobacterium tuberculosis (Mtb) strains is exacerbating the global burden of tuberculosis (TB), highlighting the urgent need for new treatment strategies for TB. Methods The recombinant adenovirus vaccine expressing cyclic di-adenosine monophosphate (c-di-AMP) phosphodiesterase B (CnpB) (rAd-CnpB), was administered to normal mice via mucosal immunization, either alone or in combination with drug therapy, to treat Mtb respiratory infections in mice.Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of antibodies in serum and bronchoalveolar lavage fluid (BALF). Real-time quantitative PCR was performed to assess the transcription levels of cytokines interferon γ(IFN-γ) and interleukin 10(IL-10) in mouse lungs. Flow cytometry was used to determine the proportions of CD4⁺ and CD8⁺ T cell subsets in the lungs and spleens. ELISA was employed to measure the levels of cytokines IFN-γ, IL-2, IL-10, inflammatory factors IL-6, and tumor necrosis factor α (TNF-α) secreted by spleen cells following antigen stimulation. The bacteria loads in the lungs and spleens of Mtb-infected mice were enumerated by plate counting methods. Resluts Intranasal immunization with rAd-CnpB induced high titers of IgG in mouse serum and the production of IgG and IgA in BALF, along with alterations in T lymphocyte subsets in the lungs and spleens. Administration of rAd-CnpB, either alone or in combination with drugs, to Mtb-infected mice significantly increased serum IgG levels as well as IgA and IgG levels in BALF. rAd-CnpB immunization promoted the secretion of CnpB-specific cytokines and inflammatory factors by splenocytes in Mtb-infected mice. However, rAd-CnpB immunotherapy, either alone or combined with drugs, did not significantly affect the bacterial loads in the lungs and spleens of mice with Mtb respiratory infections. Conclusion Mucosal immunization with rAd-CnpB induced significant mucosal, humoral and cellular immune responses in mice, and significantly enhanced CnpB-specific cellular immune responses in Mtb-infected mice.
Animals ; Adenoviridae/immunology* ; Mycobacterium tuberculosis/genetics* ; Mice ; Female ; Phosphoric Diester Hydrolases/genetics* ; Tuberculosis Vaccines/administration & dosage* ; Tuberculosis/prevention & control* ; Mice, Inbred BALB C ; Cytokines ; Lung/microbiology* ; Immunization ; Bronchoalveolar Lavage Fluid/immunology* ; Immunity, Mucosal

Objectives miR-207 has been identified as being expressed in natural killer (NK) cell exosomes that play a role in disease progression; however, to date, there are no studies specifically linking miR-207 to tuberculosis (TB). Methods Bioinformatics methods employed for prediction, followed by a dual luciferase reporter assay to determine whether lysosome-associated membrane protein 2 (LAMP2) is targeted by miR-207. The experiments were divided into four groups using the liposome transfection method (OP-LAMP2 group: co-transfected with miR-207 mimics and LAMP2 overexpression plasmid; EP group: co-transfected with mimics NC and null-loaded plasmid; siLAMP2 group: transfected with siLAMP2; and siLAMP2-NC group: transfected with siLAMP2-NC). TB infection was modeled using H37Ra-infected Ana-1 cells. The impact of LAMP2 on intracellular mycobacterial load and clearance of extracellular residual mycobacteria were assessed by tuberculosis colony-forming unit counting. Flow cytometry was used to assess the total apoptosis rate. Real-time fluorescent quantitative PCR was conducted to determine the relative expression of LAMP2, apoptosis genes, pyroptosis genes, and autophagy genes. Western blot analysis was performed to measure the relative expression of LAMP2 proteins, apoptosis proteins, pyroptosis proteins, and autophagy proteins. Results Dual luciferase reporter assay test showed that there was a targeting relationship between LAMP2 and miR-207. The transfection model was successfully constructed under real-time fluorescent quantitative PCR and Western blot statistical analysis, and microscopic observation. The infection model was successfully established under microscopic observation. Colony forming unit counting revealed that the number of colonies in the OP-LAMP2 group was lower than that in the EP group, while the number of colonies in the siLAMP2 group was higher than that in the siLAMP2-NC group. Flow cytometry assay revealed that the total apoptosis in OP-LAMP2 group was lower than that in EP group, and the total apoptosis in siLAMP2 group was higher than that in siLAMP2-NC group. Real-time fluorescence quantitative PCR and Western blot analysis revealed that the relative expression of apoptosis and pyroptosis-related proteins and genes in the control group was lower in the OP-LAMP2 group compared to the EP group, and higher in the siLAMP2 group compared to the siLAMP2-NC group. Real-time fluorescence quantitative PCR detected that the relative expression of autophagy positively regulated genes Microtubule-associated protein 1 light chain 3(LC3)and Beclin1 in the OP-LAMP2 group was higher in the OP-LAMP2 group compared to the EP group, and lower in the siLAMP2 group compared to the siLAMP2-NC group, while the relative expression of negatively regulated autophagy genes followed the opposite trend to that of autophagy positively regulated genes. The relative expression of autophagy-related proteins was consistent with the trend of autophagy genes. Conclusions miR-207 enhances macrophage apoptosis, cellular pyroptosis and inhibits autophagy, promoting survival of Mycobacterium tuberculosis by targeting the autophagy-related protein LAMP2, thus offering a novel therapeutic direction for tuberculosis.
Lysosomal-Associated Membrane Protein 2/metabolism* ; MicroRNAs/metabolism* ; Mycobacterium tuberculosis/physiology* ; Autophagy/genetics* ; Humans ; Macrophages/metabolism* ; Apoptosis/genetics* ; Tuberculosis/metabolism* ; Cell Line ; Pyroptosis/genetics*

Objective To explore the effect of miR-582-5p on Mycobacterium tuberculosis (Mtb)-infected macrophages by regulating dual specificity phosphatase 1 (DUSP1). Methods THP-1 macrophages were divided into six groups: control group, Mtb group, inhibitor-NC group, miR-582-5p inhibitor group, miR-582-5p inhibitor+si-NC group, and miR-582-5p inhibitor+si-DUSP1 group. QRT-PCR was applied to detect the gene expression of miR-582-5p and DUSP1 in cells. ELISA kit was used to detect the levels of interferon γ (IFN-γ), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and interleukin 1β (IL-1β). CCK-8 method was applied to detect cell proliferation. Flow cytometry was applied to detect cell apoptosis rate. Western blot analysis was used to measure the protein expression levels of B-cell lymphoma 2 (Bcl2), Bcl2-associated X (BAX), and cleaved-caspase 3 (c-caspase-3) in cells. In addition, the target relationship between miR-582-5p and DUSP1 was verified. Results Compared with the control group, the expression of miR-582-5p, levels of IFN-γ, IL-6, TNF-α, IL-1β, bacterial load and OD450 values (24 h, 48 h), and the protein expression of Bcl2 in macrophages were higher in the Mtb group, while the mRNA expression of DUSP1, apoptosis rate, and the protein expression levels of c-caspase-3, BAX and DUSP1 were lower. Compared with the Mtb group and the inhibitor-NC group, the above-mentioned indicators in the miR-582-5p inhibitor group were partially reversed. Down-regulation of DUSP1 expression partially reversed the inhibitory effect of down-regulation of miR-582-5p expression on Mtb-infected macrophages. Conclusion Inhibiting the expression of miR-582-5p can up-regulate DUSP1, thereby inhibiting the proliferation and inflammatory response of Mtb-infected macrophages and promoting cell apoptosis.
Humans ; Macrophages/metabolism* ; Dual Specificity Phosphatase 1/metabolism* ; MicroRNAs/metabolism* ; Mycobacterium tuberculosis/physiology* ; Tuberculosis/microbiology* ; Apoptosis/genetics* ; THP-1 Cells ; Cell Proliferation/genetics* ; Interferon-gamma/genetics* ; Tumor Necrosis Factor-alpha/genetics* ; Interleukin-1beta/genetics*