理学最新文献

This opinion challenges the conventional view that coronavirus disease 2019 behaves as a uniformly winter-dominant respiratory infection. Analysis of multi-year surveillance data across hemispheres reveals that severe acute respiratory syndrome coronavirus-2 exhibits seasonal divergence, with consistent summer surges in tropical regions, such as India, and winter peaks in temperate climates. We propose that this pattern arises primarily from human (host) behavioural responses to multi-animal tropism to climatic (environment) extremes, which recreate high-risk indoor transmission settings under both heat and cold. Unlike influenza, severe acute respiratory syndrome coronavirus-2 (agent) combines thermal resilience, broad tissue tropism, and efficient pre-symptomatic transmission, allowing persistence beyond classical winter bounds. Recognizing coronavirus disease 2019 as a behaviourally modulated (through agent-host-environment triad) seasonal virus may help tailor regional surveillance, ventilation, and vaccination strategies in an era of accelerating climatic change.

Background: Klebsiella species are important opportunistic pathogens responsible for various hospital- and community-acquired infections. The rise of multidrug-resistant strains, especially those producing extended-spectrum beta-lactamases (ESBL) and AmpC beta-lactamases, poses a major challenge to effective antimicrobial therapy and infection control.

Aim: To determine the antimicrobial susceptibility pattern of Klebsiella isolates and to detect the presence of ESBL and AmpC beta-lactamases.

Methods: A one-year cross-sectional study was conducted on 920 Gram-negative isolates, from which 130 non-repetitive Klebsiella isolates (14.13%) were selected. Antimicrobial susceptibility testing was performed, and ESBL and AmpC production were identified using standard phenotypic confirmatory methods.

Results: Among 130 Klebsiella isolates, Klebsiella pneumoniae was the predominant species (n = 92, 70.76%). Most isolates were obtained from patients aged 45-60 years (n = 33, 25.38%) and from pus samples (n = 55, 42.3%), with the highest frequency from surgical departments (n = 36, 27.7%). Among the tested antibiotics, gentamicin showed the greatest susceptibility (n = 81, 62.3%). ESBL production was detected in 77 isolates (59.2%), while 62 isolates (47.69%) produced AmpC beta-lactamases. Co-production of ESBL and AmpC was found in 35 isolates (26.92%).

Conclusion: Klebsiella species are significant nosocomial and opportunistic pathogens characterized by high multidrug resistance, often through the production of extended-spectrum and AmpC beta-lactamases. Surveillance, confirmatory testing, and infection control guide antibiotic use and prevent spread.

Infections with certain viruses are strong risk factors for specific cancers. The human major histocompatibility complex class I chain-related genes A (MICA) and B (MICB) are polymorphic, non-classical major histocompatibility complex class I genes located within the human leukocyte antigen region. Polymorphisms in these genes have been associated with susceptibility and outcomes of several virus-associated cancers. The underlying mechanisms involve modulation of natural killer cell- and CD8+ T cell-mediated cytotoxicity by disrupting the natural killer group 2-member D-MICA/B axis. The resulting soluble forms of both MICA and MICB have recently gained attention as potential predictive biomarkers for virus-induced malignancies and disease severity. Therapeutic strategies targeting this axis show considerable promise. This minireview summarizes the genetics and biology of MICA and MICB, highlighting their emerging importance in the pathogenesis of virus-associated cancers.

Background: Acute gastroenteritis significantly affects children under five, with viral agents causing over 75% of cases. Sapovirus, from the Caliciviridae family, is increasingly recognized as a major cause of childhood diarrhea, especially in low and middle-income countries with high morbidity, hospitalization, and mortality rates.

Aim: To determine the prevalence of sapovirus infection among hospitalized pediatric patients in Asia.

Methods: This study conducted a systematic review to investigate the presence of sapovirus in hospitalised pediatric patients suffering from acute gastroenteritis across Asian countries. The articles were retrieved from Scopus, PubMed, and Web of Science. The review followed PRISMA guidelines and was registered with PROSPERO (No. CRD420251029792). The quality of individual studies was assessed using Joanna Briggs Institute guidelines.

Results: A total of 39 studies with 30800 observations and 567 sapovirus-positive cases were analyzed. The pooled prevalence of sapovirus in hospitalized pediatric patients was 1.73% (95% confidence interval: 1.33%-2.25%). Substantial heterogeneity was observed (I ² = 84.9%), supporting the use of a random-effects model. Sensitivity analysis using 32 high-quality studies yielded a consistent prevalence of 1.74% (95% confidence interval: 1.31%-2.31%), reinforcing the robustness of the findings.

Conclusion: In Asian countries, sapovirus has been detected in hospitalized pediatric patients with a pooled prevalence rate of 1.73%, indicating its ongoing circulation and potential public health relevance in the region. Despite variability, consistent findings from sensitivity analysis underscore the need for enhanced surveillance and water quality monitoring to reduce public health risks.

Paediatric gut microbiome research has long been bacteriocentric, overlooking the extensive viral component known as the gut virome. Composed of bacteriophages, eukaryotic viruses, and endogenous viral elements, the paediatric gut virome is the most abundant and genetically diverse biological entity in the intestine. Emerging evidence indicates that the virome is a key regulator of microbial ecology, immune maturation, and systemic physiological programming during early life. This narrative review synthesizes current knowledge on the establishment, development, and functional roles of the paediatric gut virome, with emphasis on its interactions with the bacterial microbiome and host immune system. We highlight how early-life viral exposures influence mucosal immune imprinting, epithelial barrier integrity, and immune tolerance, particularly during the first 1000 days of life. Virome dysbiosis is increasingly associated with paediatric gastrointestinal disorders, including inflammatory bowel disease, necrotizing enterocolitis, celiac disease, and functional gastrointestinal disorders. Beyond the gut, the virome also contributes to metabolic regulation, type 1 diabetes risk, and gut-brain axis signaling, influencing neurodevelopment. Mechanistic pathways involving phage-mediated bacterial modulation, innate immune sensing, cytokine signaling, and metabolic intermediates are discussed, positioning the paediatric gut virome as a central regulator of gastrointestinal and systemic homeostasis.

Influenza, respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus 2 continue to cause substantial morbidity and mortality. Currently licensed intramuscular (IM) vaccines effectively reduce severe disease and death but only partially suppress infection and transmission because they induce limited immunity in the respiratory mucosa. This minireview summarizes next-generation mucosal vaccines for respiratory viruses, focusing on the immunological correlates of protection, platform design, and clinical translation. The literature was identified through focused searches of PubMed and Scopus, prioritizing human studies and late-stage preclinical data published between 2000 and 2025. We outline the key mucosal immune correlates required to block viral entry at the airway epithelium, including secretory IgA and tissue-resident memory T cells, and review advances across major vaccine platforms. Current clinical experience with coronavirus disease 2019, influenza, and RSV mucosal vaccines is discussed, along with challenges related to immune measurement, delivery optimization, evaluation of transmission outcomes, and scalable global implementation, including heterologous systemic-mucosal prime-boost strategies. Overall, accumulating evidence positions mucosal vaccination as a promising complement to IM vaccines, with the potential to shift respiratory virus control from disease mitigation to prevention of infection and transmission.

Background: Low-level viremia (LLV) defined as [human immunodeficiency virus (HIV)-RNA 51-999 copies/mL] has been associated with an increased risk of drug resistance and treatment failure. Advances in next-generation sequencing enabled the detection of drug resistance mutations (DRM) among people with LLV. However, evidences remain limited in low-income and middle-income countries (LMIC) where surveillance is most needed to inform global epidemic control strategies.

Aim: To determine the prevalence of HIV DRM among people living with HIV who have LLV in low- and middle-income countries.

Methods: PubMed, Cochrane Library, and EMBASE were systematically searched for articles published between January 2015 and May 2025. Studies were included if they reported DRM among adolescents and/or adults with LLV in LMIC. Mutations were interpreted using Stanford University HIV Drug Resistance Database. Prevalence of DRM was computed as the proportion of resistance mutations among successfully sequenced samples. Pooled estimates of resistance mutation and 95%CI were calculated using random-effects models with stratified analyses comparing mutations by geographic location (Africa vs Asia).

Results: Twenty studies including 7613 people with LLV were included. Of these, 5252 (73.9%) had their samples successfully sequenced. Eleven studies were from Africa and nine from Asia. Overall, the pooled prevalence of DRM was 50.4% (95%CI: 38.3-62.5) with a significantly higher prevalence observed among Africa studies compared to Asia's (58.0% vs 40.7%; P < 0.0001). The prevalence of mutations associated with nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitor were 44.6% (95%CI: 34.8-54.4), and 50.9% (95%CI: 41.4-60.4) respectively and were significantly higher in Africa than in Asia. Protease inhibitor associated mutations were also common in Africa than in Asia (7.3% vs 4.1%; P < 0.001), though the overall prevalence remains low.

Conclusion: Most individuals with LLV have resistance mutations and remain on a failed regimen over an extended period. Because resistance testing is not routinely performed in LMIC, lowering the viral failure threshold may improve timely switching to effective regimens, preserve treatment options, and reduce resistance accumulation in high HIV burden regions.

In the past 40 years, much effort has been made to develop a vaccine that can prevent human immunodeficiency virus (HIV) infection. But till today, this continues to be an unresolved challenge. The main obstacle in developing a vaccine is the ability of the virus to mutate at a swift rate, thereby evading the immune system. This has dramatically slowed the progress in the development of an HIV vaccine. Previous studies, like RV144, have demonstrated limited protection. Current trials, such as Imbokodo and Mosaico, have shown that the vaccines used were safe but did not demonstrate efficacy against the HIV-1 virus. With the advent of mRNA vaccines and broad neutralising antibodies, research has shown some progress in developing a promising candidate vaccine. Recently, the use of mosaic antigens and germline-targeting techniques has shed light on the development of a promising candidate vaccine. These techniques educate the immune system slowly. This review tracks the progress of HIV vaccine development to date and examines the most promising new strategies that could ultimately lead to the development of an efficacious vaccine.

Background: Dengue fever remains a major cause of acute febrile illness in India, particularly in rural areas where diagnostic facilities are limited. Early detection using point-of-care tests helps guide timely management and reduce unnecessary antibiotic use.

Aim: To determine the seroprevalence and clinical profile of dengue infection among acute febrile patients attending a rural tertiary care hospital in Maharashtra.

Methods: A prospective cross-sectional study was conducted at Ashwini Rural Medical College Hospital and Research Centre, Solapur from May to October 2025. A total of 320 consecutive patients presenting with acute fever of ≤ 7 days duration prior to hospital presentation were enrolled. Patients of all age groups were included. Serum samples were tested for dengue NS1 antigen and anti-dengue IgM and IgG antibodies using a commercial rapid test (Manufacturer: Meril diagnostics; Meriscreen dengue NS1 antigen and IgM + IgG antibodies). A 10% subset (n = 32) was tested by enzyme-linked immunosorbent assay (ELISA) for quality assurance. Patients were classified as recent dengue (NS1+ and/or IgM+), probable secondary infection (IgM+ IgG+), past exposure (IgG+ IgM-), or negative (NS1- IgM-). Clinical data and outcomes were recorded. Statistical analysis included χ ², Mann-Whitney U, and logistic regression (α = 0.05), adjusting for age, sex, platelet count, total leukocyte count, and presence of rash.

Results: Overall, 28% (90/320) had evidence of recent dengue, while 35% (112/320) showed IgG positivity, and 10% (32/320) had probable secondary infection. Median platelet count was significantly lower in the recent dengue group [78000/mm³; interquartile range (IQR): 55000-110000] compared with non-dengue patients (210000/mm³; IQR: 160000-240000; P < 0.001). The most common symptoms were headache (68%), myalgia (61%), and retro-orbital pain (44%). Antibiotic use prior to testing was 60%; among those diagnosed with dengue, a relative 25% reduction in antibiotic prescriptions was observed following laboratory confirmation. Quality assurance analysis showed rapid test sensitivity of 92%, specificity of 95%, and Cohen's kappa of 0.85 vs ELISA. Logistic regression identified thrombocytopenia (< 100000/mm³) [adjust odds ratio (aOR) 5.2; 95%CI: 2.4-10.9] and rash (aOR 3.6; 95%CI: 1.8-7.0) as independent predictors of dengue positivity.

Conclusion: A substantial proportion of acute febrile cases in this rural setting were due to dengue, highlighting the utility of NS1/IgM rapid tests for early diagnosis where molecular facilities are unavailable. Integrating rapid dengue testing into routine fever evaluation can improve case detection and rationalize antibiotic use.

Liver transplantation (LT) remains the only curative therapy in patients with end stage liver disease. With improvement in surgical techniques and immunosuppression protocols, both 1-year and 5-year survival have improved significantly. Similarly, recurrent hepatitis B virus and hepatitis C virus infection and consequent graft failure have become a thing of the past in the last few decades with the availability of highly effective nucleotide analogues and directly acting antivirals, respectively. However, infection with non-hepatotrophic viruses (e.g., cytomegalovirus and Epstein-Barr virus) remains an important cause of graft failure and rejection, leading to increased morbidity and mortality. Chronic hepatitis E virus infection is also an emerging cause of viral hepatitis and liver failure in these patients. The key to successful management is early diagnosis and institution of appropriate antiviral therapy. In addition, the immunosuppression must be modified to maintain a balance between aggravating viral infection and rejection. The key purpose of this article is to provide an updated overview of various hepatotropic and non-hepatotropic viral hepatitis in patients undergoing LT. Risk factors, Clinical presentation, and diagnosis of viral hepatitis in LT settings will be discussed in detail. Recurrent hepatitis B virus and hepatitis C virus infection in transplanted grafts will also be described. Finally, the use of vaccination and immunoglobulin to prevent the development of these infections will also be described.