Priscilla Rupali

Salmonella Typhi is an invasive pathogen with sustained bacteraemia and intracellular persistence, requiring therapy that achieves systemic exposure and intracellular penetration. Clinical efficacy should remain central to therapeutic decision-making, while pharmacokinetic/pharmacodynamic (PK/PD) analyses provide complementary insights into dose optimization and the pharmacological limitations of candidate therapies. Oral therapy remains central to typhoid fever management, particularly in South and Southeast Asia, where most patients are managed in the outpatient setting. However, the emergence of MDR and extensively drug-resistant (XDR) S. Typhi has substantially narrowed the available oral treatment options. Azithromycin remains the only widely available oral agent with established clinical efficacy, but emerging resistance threatens its continued utility. Several alternative oral agents, including mecillinam, faropenem, tebipenem, fosfomycin and β-lactam/β-lactamase inhibitor combinations, demonstrate favourable in vitro activity against S. Typhi. However, robust clinical efficacy and contemporary PK/PD data are lacking to support their use against MDR and XDR S. Typhi. Addressing these evidence gaps through integrated PK/PD investigations and prospective clinical trials will be essential to expand the oral therapeutic armamentarium for typhoid fever.

Acute bacterial meningitis (ABM) is a life-threatening condition requiring prompt antibiotic administration to reduce mortality and neurological sequelae.

India continues to face a significant gap between organ demand and supply, primarily due to low deceased organ donation rates and limited public awareness. The deceased donor rate remains 0.77 per million population (PMP), contributing to only 15% of transplants, with only anecdotal reports of donation after circulatory death. In contrast, living donor transplants have increased to 9.4 PMP. Globally, India ranks first in living donor transplants, third in total transplants, and 68th in deceased donor transplants. A total of 682 kidney transplant centers are registered under the National Organ and Tissue Transplant Organization (NOTTO), with a predominant concentration in the private sector (87%) and only 13% in government hospitals. Gender disparities in transplantation remain striking, underpinned by longstanding socio-economic and cultural inequities. Between 2019 and 2023, female recipients constituted only 30% of all living donor kidney transplants, even as women represented 66.2% of donors. The overall proportion of female recipients rose modestly from 28% in 2019 to 36.8% in 2023. Globally, men accounted for 64% of all recipients, with India ranked 59th among 78 countries for male dominance among living donors. Infrastructural limitations persist, with nearly 80% of immunology laboratories in metropolitan areas. Access to transplant pathology, infectious disease specialists, and advanced diagnostics remains sparse in tier 2 and 3 cities. Policy reforms—including amendments to the Transplantation of Human Organs and Tissues Act, establishment of State and Regional Organ and Tissue Transplant Organizations, and centralized coordination by NOTTO—aim to enhance access and equity. The NOTTO Chintan Shivir 2024 emphasized digital registries and protocol standardization. While innovations such as ABO-incompatible and multicenter kidney-paired donation are advancing, broader systemic reforms are essential for long-term equity and sustainability.

Purpose of review: Neurological manifestations of dengue (NeuroDengue) are uncommon but can often mimic those of other tropical infections. This review aims to present new insights on dengue encephalitis, emphasizing pathogenesis, clinical features, and diagnostic challenges. We highlight unique neuroimaging patterns, observed through MRI, which may aid in diagnosing NeuroDengue. The aim is to significantly enhance early recognition and management of this underreported but severe complication of dengue, providing valuable insights for healthcare professionals. Recent findings: Recent research has improved our understanding of dengue encephalitis and the neurotropism of the dengue virus in regions such as the thalamus, basal ganglia, and cortex. Notable MRI findings include the ‘double doughnut’ sign and microhaemorrhages, although these findings are nonspecific and may also appear in other flavivirus encephalitides. A definitive diagnosis requires a positive cerebrospinal fluid (CSF) PCR for the dengue virus, often combined with antibody testing in both CSF and serum. Additionally, elevated levels of IL-6 and TNF-α in CSF indicate enhanced inflammatory responses, which strengthens the early identification of dengue encephalitis and informs potential management strategies. Summary: Evidence affirms the neurotropic nature of dengue, confirmed by positive CSF PCR results. MRI typically reveals T2 hyperintensities in specific brain areas, along with the presence of micro-haemorrhages, and the ‘double doughnut’ sign. Recent advancements in diagnostics include analysing CSF dengue antibody indices and neuroinflammatory markers. Dengue serotypes 2 and 3 exhibit heightened neurovirulence, with seizures occurring in 30–40% of cases. While supportive management with fluids is crucial, a subset of patients may benefit from intravenous, immunoglobulin (IVIG) and steroids. Early identification of dengue encephalitis could significantly improve patient outcomes.

An increasing complexity of organ transplantation, newer immunosuppressives, and an expanded donor pool requires a well‐trained multidisciplinary workforce with surgeons, physicians, and infectious diseases (ID) physicians working together. In most countries, solid organ transplantation preceded the development of ID as a specialty leading to a lag in transplant infectious diseases (TID) physicians being a member of this team. This gap is further widened in low middle‐income countries (LMIC) like India, where there is a dearth of laboratory facilities, which are essential for pretransplant screening and diagnosis of posttransplant infections. India though an LMIC does large volumes of organ and bone marrow transplantations. This article examines the current state of ID and TID training in India with an emphasis on the need for a structured and standardized educational pathway for future transplant professionals. Drawing on examples from existing programs and workforce data using a qualitative survey, we identify paramount challenges such as inconsistent exposure during medical and surgical training, limited access to transplant‐specific education, and insufficient support for career development in transplant‐related specialties. We propose a strategic framework to address these challenges with an emphasis on early exposure, interprofessional education, mentorship, and the integration of transplant content within undergraduate and postgraduate curricula. By encouraging a comprehensive national strategy, we aspire to bridge this training gap, ensuring workforce sustainability and ultimately improving patient outcomes for those awaiting transplantation.

Introduction: According to WHO long COVID is defined as a continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation. We followed up patients after an episode of acute COVID-19 for 1 year after hospital discharge from different parts of India. Methods: This was a multi-centric study among patients ≥18 years hospitalized with COVID-19, which recruited patients at 6 weeks after hospital discharge (baseline). Quantitative data on demographics, pre-existing co-morbidities, risk factors, signs and symptoms and hospital parameters during acute COVID-19 infection were noted at baseline. They were followed up and data collected telephonically thereafter at 3–6, 6–9 and 9–12 months regarding self-reported persistence of symptoms. A qualitative component included face to face in-depth interviews to elicit information on perceived health problems, quality of life and financial burden due to COVID-19. Results: A total of 315 patients were enrolled, with the majority being males (59.4%). The median age was 52 years (IQR 40, 63). The prevalence of long COVID was 16.5%. At 6 weeks and 12 months, 35.2% and 25.9% of patients, reported more than one new symptom that affected their quality of life. Shortness of breath was common at each time point, persistent muscle pain and weakness waxed and waned. Variables at 6 weeks post discharge (baseline) such as shortness of breath (OR 2.22 CI 1.06–4.65, p = <0.05), cough (OR 6.93, CI 2.36–20.30, p = <0.05), fatigue (OR 2.34, CI 1.05–5.23, p = <0.05), and weight loss (OR 2.90, CI 1.30–6.49, p = <0.05) were significantly associated with long COVID. Conclusion: We found that long COVID was noted in 16.5% patients who self reported non – recovery at 1 year. Physical symptoms, mental health issues and mobility were persistent in a significant number of patients following an initial recovery from an acute COVID-19 infection. In 25.9% of patients more than 1 symptom was reported at 1 year after COVID-19. We urgently need therapeutic interventions which can improve the quality of life in these patients.

Background & Aim Tuberculous paradoxical reaction in HIV-negative patients is rare and not well understood. This study aimed to determine the incidence of paradoxical reaction and identify clinical and immunological predictors contributing to its development. Methods Patients with tuberculous lymphadenitis on anti-tuberculous therapy were monitored for paradoxical reaction. Clinical, histopathological, microbiological, and immunological parameters of paradoxical reaction (n=10) and no paradoxical reaction (n=66) groups were analysed at baseline, 2 months, and 6 months. Peripheral blood mononuclear cells from paradoxical reaction (n=9) and no paradoxical reaction (n=13) patients were stimulated with TB-ESAT peptide, and mRNA expressions of cytokines (IL-4, IL-10, IL-12, TNF-α, IFN-γ) and transcription factors (T-bet, GATA-3) were quantified. Results Paradoxical reaction incidence was 5.7% (4/70); six patients presented with paradoxical reaction at baseline. The mean paradoxical reaction onset was 3.25 months. Absence of necrosis at baseline was a significant predictor (OR: 0.069; p=0.039). IL-10 mRNA at 2 months and IL-12 mRNA at 6 months increased in the paradoxical reaction compared to no paradoxical reaction (p=0.05). In paradoxical reaction, baseline T-bet mRNA correlated with IFN-γ (r=0.79, pConclusion Differential Th1/Th2 regulation driven by transcriptional factors alters cytokine expression, influencing paradoxical reaction. Further transcriptomic/proteomic studies are needed to elucidate immune mechanisms for precise therapeutic intervention.