Publications by authors named "Syed Hissar"

Background: Children with tuberculous meningitis (TBM) present with diagnostic challenges as they often have atypical clinical features.

Objective: To describe the baseline characteristic features of children diagnosed with central nervous system (CNS) TB (TBM and tuberculoma).

Design: Retrospective descriptive study.

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  • Tuberculosis (TB) is a major health issue in India, especially in patients with diabetes mellitus (DM), creating a serious challenge known as TB-PDM.
  • The study analyzed the effects of DM on the immune response in patients with pulmonary TB by measuring various cytokine and chemokine levels in blood samples.
  • Results revealed that coexisting TB and PDM lead to higher mycobacterial loads and increased cytokine and chemokine levels, suggesting that glycemic control is crucial for managing this complicated relationship between the two diseases.
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A natural infection or a vaccination can initially prime the immune system to form immunological memory. The immunity engendered by vaccination against COVID-19 versus natural infection with SARS-CoV-2 has not been well studied in the Indian population. In this study, we compared the immunity conferred by COVID-19 vaccines to naturally acquired immunity to SARS-CoV-2 in a South Indian population.

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Xpert MTB/RIF is recommended for the diagnosis of tuberculosis (TB) in children. We determined the performance of Xpert MTB/RIF in the diagnosis of pulmonary TB in children. The characteristics of children influencing Xpert MTB/RIF positivity were explored.

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  • Tuberculosis lymphadenitis is a common form of extra-pulmonary TB, traditionally requiring six months of treatment, but this study explored a potential four-month regimen using ofloxacin.
  • The trial involved adult TB patients randomly assigned to either a four-month ofloxacin-based treatment or a traditional six-month regimen, with outcomes assessed based on TB recurrence and treatment success.
  • Results showed the four-month regimen was as effective and safe as the six-month control, with similar rates of favorable response and manageable side effects, making it a promising alternative.
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Introduction: The assessment of tuberculosis (TB) treatment outcomes predominantly relies on sputum culture conversion status. To enhance treatment management, it is crucial to identify non-sputum-based biomarkers that can predict unfavorable outcomes. Cytokines are widely studied as diagnostic biomarkers for active TB.

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Background: It has been reported that differential diagnosis of bacterial or viral pneumonia and tuberculosis (TB) in infants and young children is complex. This could be due to the difficulty in microbiological confirmation in this age group. In this study, we aimed to assess the utility of a real-time multiplex PCR for diagnosis of respiratory pathogens in children with pulmonary TB.

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Background: Children with human immunodeficiency virus (HIV, CWH) are at high risk of tuberculosis (TB) and face poor outcomes, despite antiretroviral therapy (ART). We evaluated outcomes in CWH and children not living with HIV treated for nonsevere TB in the SHINE trial.

Methods: SHINE was a randomized trial that enrolled children aged <16 years with smear-negative, nonsevere TB who were randomized to receive 4 versus 6 months of TB treatment and followed for 72 weeks.

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Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare manifestation of Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) infection that can result in increased morbidity and mortality. Mounting evidence describes sex disparities in the clinical outcomes of coronavirus disease 2019 (COVID-19). However, there is a lack of information on sex-specific differences in immune responses in MIS-C.

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Background: Multisystem inflammatory syndrome (MIS) in children is considered to be a post-infectious complication of COVID-19. T-cell responses in children with this condition have not been well-studied.

Methods: We aimed to study the immune responses in children with MIS in comparison to children with acute COVID-19 and children with other infections.

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  • This study investigates how monocyte miRNAs are involved in the immune responses during tuberculosis (TB), focusing on their expression profiles in different TB conditions, including drug-resistant TB, drug-sensitive TB, and latent TB, as well as in healthy individuals.* -
  • Using flow cytometry and NanoString profiling, researchers identified significant differences in miRNA expression, particularly noting downregulation in active TB cases and specific miRNA changes unique to drug-resistant and drug-sensitive TB.* -
  • The findings suggest that these miRNA signatures could serve as biomarkers for TB severity and drug resistance, highlighting the need for further research on their role in the immune response to tuberculosis.*
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Tuberculosis (TB) diagnosis still remains to be a challenge with the currently used immune based diagnostic methods particularly Interferon Gamma Release Assay due to the sensitivity issues and their inability in differentiating stages of TB infection. Immune markers are valuable sources for understanding disease biology and are easily accessible. Chemokines, the stimulant, and the shaper of host immune responses are the vital hub for disease mediated dysregulation and their varied levels in TB disease are considered as an important marker to define the disease status.

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Introduction: Chitinase, Indoleamine 2,3-dioxygenesae-1 (IDO-1) and heme oxygenase-1 (HO-1) are candidate diagnostic biomarkers for tuberculosis (TB). Whether these immune markers could also serve as predictive biomarkers of unfavorable treatment outcomes in pulmonary TB (PTB) is not known.

Methods: A cohort of newly diagnosed, sputum culture-positive adults with drug-sensitive PTB were recruited.

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Tuberculosis (TB) elimination is possible with the discovery of accurate biomarkers that define the stages of infection. Drug-resistant TB impair the current treatment strategies and worsen the unfavourable outcomes. The knowledge on host immune responses between drug-sensitive and drug-resistant infection is inadequate to understand the pathophysiological differences and disease severity.

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Introduction: Multisystem Inflammatory Syndrome in children (MIS-C) is a serious inflammatory sequela of SARS-CoV2 infection. The pathogenesis of MIS-C is vague and matrix metalloproteinases (MMPs) may have an important role. Matrix metalloproteinases (MMPs) are known drivers of lung pathology in many diseases.

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The clinical presentation of MIS-C overlaps with other infectious/non-infectious diseases such as acute COVID-19, Kawasaki disease, acute dengue, enteric fever, and systemic lupus erythematosus. We examined the ex-vivo cellular parameters with the aim of distinguishing MIS-C from other syndromes with overlapping clinical presentations. MIS-C children differed from children with non-MIS-C conditions by having increased numbers of naïve CD8+ T cells, naïve, immature and atypical memory B cells and diminished numbers of transitional memory, stem cell memory, central and effector memory CD4+ and CD8+ T cells, classical, activated memory B and plasma cells and monocyte (intermediate and non-classical) and dendritic cell (plasmacytoid and myeloid) subsets.

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A major challenge in tuberculosis is identifying correlates of a protective immune response. The Mycobacterial Growth Inhibition Assay (MGIA) is a functional assay providing an integrated measure of the host immune response to mycobacteria. However, its feasibility is limited by reliance on biosafety level 3 facilities, and its performance has not been widely evaluated in TB-endemic settings.

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Background: Multisystem inflammatory syndrome in children (MIS-C) presents with inflammation and pathology of multiple organs in the pediatric population in the weeks following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Methods: We characterized the SARS-CoV-2 antigen-specific cytokine and chemokine responses in children with MIS-C, coronavirus disease 2019 (COVID-19), and other infectious diseases.

Results: MIS-C is characterized by elevated levels of type 1 (interferon-γ, interleukin [IL] 2), type 2 (IL-4, IL-13), type 17 (IL-17), and other proinflammatory cytokines (IL-1α, IL-6, IL-12p70, IL-18, and granulocyte-macrophage colony-stimulating factor) in comparison to COVID-19 and other infectious diseases following stimulation with SARS-CoV-2-specific antigens.

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The rampant increase in drug-resistant tuberculosis (TB) remains a major challenge not only for treatment management but also for diagnosis, as well as drug design and development. Drug-resistant mycobacteria affect the quality of life owing to the delayed diagnosis and require prolonged treatment with multiple and toxic drugs. The phenotypic modulations defining the immune status of an individual during tuberculosis are well established.

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Background: Microbial translocation is a known characteristic of pulmonary tuberculosis (PTB). Whether microbial translocation is also a biomarker of recurrence in PTB is not known.

Methods: We examined the presence of microbial translocation in a cohort of newly diagnosed, sputum smear, and culture positive individuals with drug-sensitive PTB.

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Background: Two thirds of children with tuberculosis have nonsevere disease, which may be treatable with a shorter regimen than the current 6-month regimen.

Methods: We conducted an open-label, treatment-shortening, noninferiority trial involving children with nonsevere, symptomatic, presumably drug-susceptible, smear-negative tuberculosis in Uganda, Zambia, South Africa, and India. Children younger than 16 years of age were randomly assigned to 4 months (16 weeks) or 6 months (24 weeks) of standard first-line antituberculosis treatment with pediatric fixed-dose combinations as recommended by the World Health Organization.

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Systemic inflammation is a characteristic feature of pulmonary tuberculosis (PTB). Whether systemic inflammation is associated with treatment failure in PTB is not known. Participants, who were newly diagnosed, sputum smear and culture positive individuals with drug-sensitive PTB, were treated with standard anti-tuberculosis treatment and classified as having treatment failure or microbiological cure.

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Background: Diagnosing tuberculosis (TB) in children is challenging due to paucibacillary disease, and lack of ability for microbiologic confirmation. Hence, we measured the plasma chemokines as biomarkers for diagnosis of pediatric tuberculosis.

Methods: We conducted a prospective case control study using children with confirmed, unconfirmed and unlikely TB.

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Background: Dispersible pediatric fixed-dose combination (FDC) tablets delivering higher doses of first-line antituberculosis drugs in World Health Organization-recommended weight bands were introduced in 2015. We report the first pharmacokinetic data for these FDC tablets in Zambian and South African children in the treatment-shortening SHINE trial.

Methods: Children weighing 4.

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Objectives: To study the association of Tissue inhibitors of matrix metalloproteinases (TIMP) levels with tuberculosis-diabetes comorbidity (TB-DM) comorbidity at baseline and in response to anti-TB treatment (ATT).

Methods: We examined the levels of TIMP-1, -2, -3 and -4 in pulmonary tuberculosis alone (TB) or TB-DM at baseline and after ATT.

Results: TIMP-1, -3 and -4 were significantly increased in TB-DM compared to TB at baseline and after ATT.

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