IL-27 maintains cytotoxic Ly6C+ γδ T cells that arise from immature precursors.

In mice, γδ-T lymphocytes that express the co-stimulatory molecule, CD27, are committed to the IFNγ-producing lineage during thymic development. In the periphery, these cells play a critical role in host defense and anti-tumor immunity. Unlike αß-T cells that rely on MHC-presented peptides to drive their terminal differentiation, it is unclear whether MHC-unrestricted γδ-T cells undergo further functional maturation after exiting the thymus. Here, we provide evidence of phenotypic and functional diversity within peripheral IFNγ-producing γδ T cells. We found that CD27+ Ly6C- cells convert into CD27+Ly6C+ cells, and these CD27+Ly6C+ cells control cancer progression in mice, while the CD27+Ly6C- cells cannot. The gene signatures of these two subsets were highly analogous to human immature and mature γδ-T cells, indicative of conservation across species. We show that IL-27 supports the cytotoxic phenotype and function of mouse CD27+Ly6C+ cells and human Vδ2+ cells, while IL-27 is dispensable for mouse CD27+Ly6C- cell and human Vδ1+ cell functions. These data reveal increased complexity within IFNγ-producing γδ-T cells, comprising immature and terminally differentiated subsets, that offer new insights into unconventional T-cell biology.

Respiratory tract infections: an update on the complexity of bacterial diversity, therapeutic interventions and breakthroughs.

Respiratory tract infections (RTIs) have a significant impact on global health, especially among children and the elderly. The key bacterial pathogens Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae, Staphylococcus aureus and non-fermenting Gram Negative bacteria such as Acinetobacter baumannii and Pseudomonas aeruginosa are most commonly associated with RTIs. These bacterial pathogens have evolved a diverse array of resistance mechanisms through horizontal gene transfer, often mediated by mobile genetic elements and environmental acquisition. Treatment failures are primarily due to antimicrobial resistance and inadequate bacterial engagement, which necessitates the development of alternative treatment strategies. To overcome this, our review mainly focuses on different virulence mechanisms and their resulting pathogenicity, highlighting different therapeutic interventions to combat resistance. To prevent the antimicrobial resistance crisis, we also focused on leveraging the application of artificial intelligence and machine learning to manage RTIs. Integrative approaches combining mechanistic insights are crucial for addressing the global challenge of antimicrobial resistance in respiratory infections.

Public Engagement as the Fifth Dimension of Outbreak Communication: Public's Perceptions of Public Health Communication during COVID-19 in India.

Public health/risk communication is the foremost responsibility of a government during a pandemic. Risk communication aims to educate people, enhance their risk perceptions to help them engage and understand the benefits of compliance with recommendations. The existing legal enforcement of recommendations in India is criticized for failing to influence the public's compliance. While existing research provides conceptual and empirical support in explaining compliance during COVID-19, we note a lack of studies that might bring out country-specific areas of improvement. We argue that value-aligned risk communication is more likely to influence the public's behavioral intentions to adopt the government's recommendations. We employed a triangulation mixed-method study to link risk communication attributes to the public's end goals and values. We triangulate these findings using the COVID score survey. We found that timeliness and transparency constitute risk communication's functional component, and empathy and trust constitute risk communication's emotional component. We found a difference in the preference of functional and emotional components among the public and health partners. Irrespective of this divide in perception, the study found that both groups unanimously noted engagement as the crucial aspect for empowerment and involvement to aid the public in teaming with the government to combat the pandemic effectively.

Multicentric Analysis of Erythromycin Resistance Determinants in Invasive Streptococcus pneumoniae; Associated Serotypes and Sequence Types in India.

Streptococcus pneumoniae is the major cause of childhood pneumonia and related deaths in India. Widespread use of erythromycin for the treatment of pneumonia has led to the emergence of erythromycin resistance. Despite this increase in erythromycin resistance, there are very little data on resistance determinants from India. Hence, we aimed to perform the molecular characterization of erythromycin-resistant invasive pneumococcal isolates in India. In this study, 250 erythromycin-resistant invasive isolates obtained from four Indian hospitals between 2014 and 2019 were included. The isolates were reconfirmed by standard CDC protocols, followed by detection of erm(B), mef(A/E) genes, and screening for mutations in 23S rRNA, ribosomal proteins L4 and L22. Among the 250 erythromycin-resistant isolates, 46% (n = 114) and 35% (n = 87) carried the mef(A/E) gene and erm(B) gene, respectively; both genes were present in 8% (n = 20) of the isolates and 12% (n = 29) of the studied strains did not bear any of them. The major mutations associated with erythromycin resistance in 23S rRNA, such as A2060C, A2061G, and C2613G, were absent. The predominant serotypes were 19F, 14, 23F, 6A, 6B, 19A, and 9V. The major clonal complexes were CC320, followed by CC230 and CC63. The predominant gene was mef(A/E), and most of the serotypes were PCV13 (54%). This study contributes to the baseline understanding of the erythromycin resistance determinants associated with the serotypes and sequence types (ST) of Indian invasive S. pneumoniae.

Designing Dynamic Interventions to Improve Adherence in Pediatric Long-Term Treatment - The Role of Perceived Value of the Physician by Primary Caregivers.

Primary Caregivers are the fulcrum in the physician-caregiver-child triad. Existing literature discusses static multi-component interventions in detail. In long-term treatments, dynamic intervention design is needed as the environment and situations of the families are dynamic. The objectives of this study are (a) to identify the components of the primary caregiver's perception of the physician's value with reference to the effectiveness of consultation and relationships with the former and with the child; (b) to establish the role of this perception in designing dynamic interventions, and (c) to describe the perception's potential influence on adherence. A PRISMA, chronological, and morphological analysis of the literature is carried out about caregivers' adherence in the pediatric long-term treatment context. We define communication and consultation as the functional, whereas relationship as the emotional component of the caregiver's perception of the physician. We propose a theoretical model that incorporates intervention as an integral component of care. Adherence happens as a response to changing situations and hence fluctuates. Hence, a dynamic intervention design to benefit the child should be incorporated into care through the caregiver-physician bridge. Future research should explore how intervention needs change and the driving reasons for understanding the static and dynamic components of interventions.

Correlation of SARS-CoV-2 Serology and Clinical Phenotype Amongst Hospitalised Children in a Tertiary Children's Hospital in India.

INTRODUCTION: Children usually present with minimal or no symptoms of COVID-19 infection. Antibody responses to SARS-CoV-2 in children from low- and middle-income countries (LMIC) have not been well described. We describe the prevalence of anti-SARS-CoV-2 antibodies and clinical phenotype of seropositive children admitted to a tertiary children's hospital in South India. METHODS: To determine the seropositivity and describe the clinical characteristics of COVID-19 infection amongst hospitalised children, we performed a prospective clinical data collection and blood sampling of children admitted to Kanchi Kamakoti CHILDS Trust Hospital, Chennai, India over 4 months of the COVID-19 pandemic. In seropositive children, we compared antibody titres between children with and without PIMS-TS. RESULTS: Of 463 children, 91 (19.6%) were seropositive. The median (range) age of seropositive children was 5 years (1 month-17 years). Clinical presentation was consistent with Paediatric inflammatory multisystem syndrome associated or related with SARS-CoV-2 infection (PIMS-TS) in 48% (44/91) of seropositive children. The median (range) antibody titre was 54.8 (11.1-170.9) AU/ml among all seropositive children. The median antibody titre among the children with PIMS-TS (60.3 AU/mL) was significantly (p = 0.01) higher when compared to the children without PIMS-TS (54.8 AU/mL). CONCLUSION: We describe the antibody responses to SARS-CoV-2 amongst hospitalised children in a LMIC tertiary children's hospital. Almost half of the seropositive children had PIMS-TS. Antibody levels may be helpful in the diagnosis and disease stratification of PIMS-TS. LAY SUMMARY: Children usually present with minimal or no symptoms of COVID-19 infection. However, Multisystem Inflammatory Syndrome in Children (MIS-C) or Paediatric inflammatory multisystem syndrome associated or related with SARS-CoV-2 infection (PIMS-TS) has emerged as a distinctive paediatric illness related to SARS-CoV-2. Recently, antibody testing for SARS-CoV-2 is being used increasingly as a diagnostic test for PIMS-TS. However, data on the antibody responses to SARS-CoV-2 in children are sparse. We, therefore, attempted to identify the seropositivity and describe the clinical spectrum of COVID-19 infection amongst infants and children getting hospitalised in a children's hospital in south India. Nearly one-fifth of the hospitalised children tested serology positive over 4 months. Antibody levels in children with PIMS-TS were significantly higher in comparison to the other two groups (acute COVID-19 infection and children without PIMS-TS). Results from our study suggest that all children are at risk of COVID-19 infection though they may present with mild illness or no symptoms. We also observed that antibody testing may have a possible role in diagnosis of PIMS-TS.

Catalyst-Substrate Effects on Biocompatible SABRE Hyperpolarization.

The hyperpolarization technique, Signal Amplification by Reversible Exchange (SABRE), has the potential to improve clinical diagnosis by making molecular magnetic resonance imaging in vivo a reality. Essential to this goal is the ability to produce a biocompatible bolus for administration. We seek here to determine how the identity of the catalyst and substrate affects the cytotoxicity by in vitro study, in addition to reporting how the use of biocompatible solvent mixtures influence the polarization transfer efficiency. By illustrating this across five catalysts and 8 substrates, we are able to identify routes to produce a bolus with minimal cytotoxic effects.

Nasopharyngeal carriage of Streptococcus pneumoniae serotypes among children in India prior to the introduction of pneumococcal conjugate vaccines: a cross-sectional study.

BACKGROUND: Streptococcus pneumoniae is a major cause of pneumonia, meningitis, and other serious infections among children in India. India introduced the 13-valent pneumococcal conjugate vaccine (PCV) in several states in 2017, and is expected to expand to nationwide coverage in the near future. To establish a baseline for measuring the impact of PCV in India, we assessed overall and serotype-specific nasopharyngeal carriage in two pediatric populations. METHODS: A cross-sectional study was conducted in Palwal District, Haryana, from December 2016 to July 2017, prior to vaccine introduction. Children 2-59 months of age with clinical pneumonia seeking healthcare and those in the community with no clear illness were targeted for enrollment. A nasopharyngeal swab was collected and tested for pneumococcus using conventional culture and sequential multiplex PCR. Isolates were tested for antimicrobial resistance using an E test. Children were considered colonized if pneumococcus was isolated by culture or PCR. The prevalence of pneumococcal and serotype-specific colonization was compared between groups of children using log-binomial regression. RESULTS: Among 601 children enrolled, 91 had clinical pneumonia and 510 were community children. The proportion colonized with S. pneumoniae was 74.7 and 54.5% among children with clinical pneumonia and community children, respectively (adjusted prevalence ratio: 1.38; 95% confidence interval: 1.19, 1.60). The prevalence of PCV13 vaccine-type colonization was similar between children with clinical pneumonia (31.9%) and community children (28.0%; p = 0.46). The most common colonizing serotypes were 6A, 6B, 14, 19A, 19F, and 23F, all of which are included in the PCV13 vaccine product. Antimicrobial resistance to at least one drug was similar between isolates from children with clinical pneumonia (66.1%) and community children (61.5%; p = 0.49); while resistance to at least two drugs was more common among isolates from children with clinical pneumonia (25.8% vs. 16.4%; p = 0.08). Resistance for all drugs was consistently higher for PCV13 vaccine-type serotypes compared to non-vaccine serotypes in both groups. CONCLUSION: This study provides baseline information on the prevalence of serotype-specific pneumococcal colonization among children prior to the introduction of PCV in India. Our results suggest a role for pneumococcal vaccines in reducing pneumococcal colonization and antimicrobial resistant isolates circulating in India.

Acute undifferentiated fever in India: a multicentre study of aetiology and diagnostic accuracy.

BACKGROUND: The objectives of this study were to determine the proportion of malaria, bacteraemia, scrub typhus, leptospirosis, chikungunya and dengue among hospitalized patients with acute undifferentiated fever in India, and to describe the performance of standard diagnostic methods. METHODS: During April 2011-November 2012, 1564 patients aged ≥5 years with febrile illness for 2-14 days were consecutively included in an observational study at seven community hospitals in six states in India. Malaria microscopy, blood culture, Dengue rapid NS1 antigen and IgM Combo test, Leptospira IgM ELISA, Scrub typhus IgM ELISA and Chikungunya IgM ELISA were routinely performed at the hospitals. Second line testing, Dengue IgM capture ELISA (MAC-ELISA), Scrub typhus immunofluorescence (IFA), Leptospira Microscopic Agglutination Test (MAT), malaria PCR and malaria immunochromatographic rapid diagnostic test (RDT) Parahit Total™ were performed at the coordinating centre. Convalescence samples were not available. Case definitions were as follows: Leptospirosis: Positive ELISA and positive MAT. Scrub typhus: Positive ELISA and positive IFA. Dengue: Positive RDT and/or positive MAC-ELISA. Chikungunya: Positive ELISA. Bacteraemia: Growth in blood culture excluding those defined as contaminants. Malaria: Positive genus-specific PCR. RESULTS: Malaria was diagnosed in 17% (268/1564) and among these 54% had P. falciparum. Dengue was diagnosed in 16% (244/1564). Bacteraemia was found in 8% (124/1564), and among these Salmonella typhi or S. paratyphi constituted 35%. Scrub typhus was diagnosed in 10%, leptospirosis in 7% and chikungunya in 6%. Fulfilling more than one case definition was common, most frequent in chikungunya where 26% (25/98) also had positive dengue test. CONCLUSIONS: Malaria and dengue were the most common causes of fever in this study. A high overlap between case definitions probably reflects high prevalence of prior infections, cross reactivity and subclinical infections, rather than high prevalence of coinfections. Low accuracy of routine diagnostic tests should be taken into consideration when approaching the patient with acute undifferentiated fever in India.

De novo DNA Methyltransferases Dnmt3a and Dnmt3b regulate the onset of Igκ light chain rearrangement during early B-cell development.

Immunoglobulin genes V(D)J rearrangement during early lymphopoiesis is a critical process involving sequential recombination of the heavy and light chain loci. A number of transcription factors act together with temporally activated recombinases and chromatin accessibility changes to regulate this complex process. Here, we deleted the de novo DNA methyltransferases Dnmt3a and Dnmt3b in early B cells of conditionally targeted mice, and monitored the process of V(D)J recombination. Dnmt3a and Dnmt3b deletion resulted in precocious recombination of the immunoglobulin κ light chain without impairing the differentiation of mature B cells or overall B-cell development. Ex vivo culture of IL-7 restricted early B-cell progenitors lacking Dnmt3a and Dnmt3b showed precocious Vκ-Jκ rearrangements that are limited to the proximal Vκ genes. Furthermore, B-cell progenitors deficient in Dnmt3a and Dnmt3b showed elevated levels of germline transcripts at the proximal Vκ genes, alterations in methylation patterns at Igκ enhancer sites and increased expression of the transcription factor E2A. Our data suggest that Dnmt3a and Dnmt3b are critical to regulate the onset of Igκ light chain rearrangement during early B-cell development.

Single-molecule sequencing reveals the molecular basis of multidrug-resistance in ST772 methicillin-resistant Staphylococcus aureus.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital-associated infection, but there is growing awareness of the emergence of multidrug-resistant lineages in community settings around the world. One such lineage is ST772-MRSA-V, which has disseminated globally and is increasingly prevalent in India. Here, we present the complete genome sequence of DAR4145, a strain of the ST772-MRSA-V lineage from India, and investigate its genomic characteristics in regards to antibiotic resistance and virulence factors. RESULTS: Sequencing using single-molecule real-time technology resulted in the assembly of a single continuous chromosomal sequence, which was error-corrected, annotated and compared to nine draft genome assemblies of ST772-MRSA-V from Australia, Malaysia and India. We discovered numerous and redundant resistance genes associated with mobile genetic elements (MGEs) and known core genome mutations that explain the highly antibiotic resistant phenotype of DAR4145. Staphylococcal toxins and superantigens, including the leukotoxin Panton-Valentinin Leukocidin, were predominantly associated with genomic islands and the phage φ-IND772PVL. Some of these mobile resistance and virulence factors were variably present in other strains of the ST772-MRSA-V lineage. CONCLUSIONS: The genomic characteristics presented here emphasize the contribution of MGEs to the emergence of multidrug-resistant and highly virulent strains of community-associated MRSA. Antibiotic resistance was further augmented by chromosomal mutations and redundancy of resistance genes. The complete genome of DAR4145 provides a valuable resource for future investigations into the global dissemination and phylogeography of ST772-MRSA-V.

Targets for intervention to improve virological outcomes for patients receiving free antiretroviral therapy in Tamil Nadu, India.

Operational research to identify factors predicting poor clinical outcomes is critical to maximize patient care and prolong first-line regimens for those receiving free antiretroviral therapy (ART) in India. We sought to identify social or clinical factors amenable to intervention that predict virological outcomes after 12 months of ART. We examined a retrospective cohort of consecutive adults initiating free nonnucleoside reverse transcriptase inhibitor-based regimens. Individuals remaining in care 12 months post-ART initiation were tested for HIV viral load and surveyed to identify barriers and facilitators to adherence, and to determine clinic travel times and associated costs. Uni- and multivariate logistic regression identified factors predicting HIV viral load >200 copies/mL after 12 months of ART. Of 230 adults initiating ART, 10% of patients died, 8% transferred out, 5% were lost to follow-up, and 174/230 (76%) completed 12 months of ART, the questionnaire, and viral load testing. HIV viral load was <200 copies/mL in 140/174 (80%) patients. In multivariate models, being busy with work or caring for others (OR 2.9, p < 0.01), having clinic transport times ≥ 3 hours (OR 3.0, p = 0.02), and alcohol use (OR 4.8, p = 0.03) predicted viral load >200 copies/mL after 12 months of ART. Clinical outcomes following ART are related to programmatic factors such as prolonged travel time and individual factors such as being busy with family or using alcohol. Simple interventions that alter these factors should be evaluated to improve clinical outcomes for populations receiving free ART in similar settings.

Computational study of the piperidine and FtsZ interaction in Salmonella Typhi: implications for disrupting cell division machinery.

FtsZ, a bacterial cell division protein, is essential for assembling the contractile Z-ring crucial in bacterial cytokinesis. Consequently, inhibiting FtsZ could impede proto-filaments, disrupting FtsZ and other associated proteins vital for cell division machinery. Conduct an in-silico drug interaction study to identify novel drug candidates that inhibit the FtsZ protein, aiming to prevent Multi-Drug Resistant (MDR) Salmonella Typhi. Data mining was performed based on piperidine compounds, which were subsequently screened for safe pharmacokinetic profiles. Compounds that met favorable drug-likeness criteria underwent virtual screening against the FtsZ drug target. Two compounds were chosen for molecular docking and molecular dynamic simulation to verify the binding affinity and stability between the target protein and the potential compounds. The 400 isoforms of piperidine analogues were curated, among them potent compound ZINC000000005416 found to possess high binding affinity (-8.49 kcal/mol) and low dissociation constant (0.597 µM). The highest binding affinity shown by ZINC000000005416 was validated by hydrogen bonds, hydrophobic interaction, and salt bridges with the functional domain of the cell division regulatory protein. Docking profiles, when correlated with molecular dynamic simulation (MDS) depicted stable trajectories and compatible conformational changes in the FtsZ-ZINC000000005416 complex. The stable simulated trajectories were validated through free-energy calculations using the Molecular Mechanics-Poisson Boltzmann Surface Area (MM/PBSA) module. Low energy conformations, although the simulation trajectory confirmed the stable ZINC000000005416-FtsZ interaction, which encouraged experimental validations. This study encourages further exploration of the compound ZINC000000005416 as a drug candidate inhibiting FtsZ protein against MDR Salmonella Typhi.Communicated by Ramaswamy H. Sarma.

Changing Landscape of Antimicrobial Resistance in Neonatal Sepsis: An in silico Analyses of Multidrug Resistance in Klebsiella pneumoniae.

BACKGROUND: Neonatal sepsis poses a critical healthcare concern, as multidrug-resistant Klebsiella pneumoniae ( K. pneumoniae ) infections are on the rise. Understanding the antimicrobial susceptibility patterns and underlying resistance mechanism is crucial for effective treatment. OBJECTIVES: This study aimed to comprehensively investigate the antimicrobial susceptibility patterns of K. pneumoniae strains responsible for neonatal sepsis using in silico tools. We sought to identify trends and explore reasons for varying resistance levels, particularly for ß-lactams and fluoroquinolone. METHODS: K. pneumoniae isolated from neonates at Kanchi Kamakoti CHILDS Trust Hospital (2017-2020) were analyzed for antimicrobial resistance. Elevated resistance to ß-lactam and fluoroquinolone antibiotics was further investigated through molecular docking and interaction analysis. ß-lactam affinity with penicillin-binding proteins and ß-lactamases was examined. Mutations in ParC and GyrA responsible for quinolone resistance were introduced to investigate ciprofloxacin interactions. RESULTS: Of 111 K. pneumoniae blood sepsis isolates in neonates, high resistance was detected to ß-lactams such as cefixime (85.91%, n = 71), ceftriaxone (84.9%, n = 106), cefotaxime (84.9%, n = 82) and fluoroquinolone (ciprofloxacin- 79.44%, n = 107). Molecular docking revealed low ß-lactam binding toward penicillin-binding proteins and higher affinities for ß-lactamases, attributing to the reduced ß-lactam efficiency. Additionally, ciprofloxacin showed decreased affinity toward mutant ParC and GyrA in comparison to their corresponding wild-type proteins. CONCLUSION: Our study elucidates altered resistance profiles in neonatal sepsis caused by K. pneumoniae , highlighting mechanisms of ß-lactam and fluoroquinolone resistance. It underscores the urgent need for the development of sustainable therapeutic alternatives to address the rising antimicrobial resistance in neonatal sepsis.

Whole genome analysis reveals unique traits of SARS-CoV-2 in pediatric patients.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to challenge the global healthcare with emerging variants and higher infectivity as well as morbidities. This study investigated potential age-related variations through genomic characterization of the virus under common clinical settings. A cohort comprising 71 SARS-CoV-2 strains from both infected infants and accompanying adults, diagnosed via RT-PCR at a tertiary pediatric hospital and research center, underwent Illumina paired-end sequencing. The subsequent analysis involved standard genomic screening, phylogeny construction, and mutational analyses. The analyzed SARSCoV- 2 strains were compared with globally circulating variants. The overall distribution revealed 67.61 % Delta, 25.7 % Omicron, and 1 % either Kappa or Alpha variants. In 2021, Delta predominated at âˆ¼ 94 %, with Alpha/Kappa accounting for around 5 %. However, in 2022, over 94 % of the samples were Omicron variants, signifying a substantial shift from Delta dominance. Delta variants constituted 69.5 % of infections in adults and 78.5 % in infants, while Omicron variants were responsible for 31 % of cases in infants and 18 % in adults. The Spike region harbored the majority of mutations, with T19R being the most prevalent mutation in the Delta lineage. Notably, the frequencies of this mutation varied between infants and adults. In Omicron samples, G142D emerged as the most prevalent mutation. Our dataset predominantly featured clade 21A and lineage B.1.617.2. This study underscores the differential clinical presentations and genomic characteristics of SARS-CoV-2 in pediatric patients and accompanying adults. Understanding the dynamic evolution of the SARS- CoV-2 in both pediatric and adults can help in strengthening prophylactic measures.

Detection of oxacillin-susceptible mecA-positive Staphylococcus aureus isolates by use of chromogenic medium MRSA ID.

Reports of oxacillin-susceptible mecA-positive Staphylococcus aureus strains are on the rise. Because of their susceptibility to oxacillin and cefoxitin, it is very difficult to detect them by using routine phenotypic methods. We describe two such isolates that were detected by chromogenic medium and confirmed by characterization of the mecA gene element.

Pharmacy and self-report adherence measures to predict virological outcomes for patients on free antiretroviral therapy in Tamil Nadu, India.

Over 480,000 individuals receive free antiretroviral therapy (ART) in India yet data associating ART adherence with HIV viral load for populations exclusively receiving free ART are not available. Additionally estimates of adherence using pharmacy data on ART pick-up are not available for any population in India. After 12-months ART we found self-reported estimates of adherence were not associated with HIV viral load. Individuals with <100% adherence using pharmacy data predicted HIV viral load, and estimates combining pharmacy data and self-report were also predictive. Pharmacy adherence measures proved a feasible method to estimate adherence in India and appear more predictive of virological outcomes than self-report. Predictive adherence measures identified in this study warrant further investigation in populations receiving free ART in India to allow for identification of individuals at risk of virological failure and in need of adherence support.

Emergence of sulphonamide resistance in azithromycin-resistant pediatric strains of Salmonella Typhi and Paratyphi A: A genomics insight.

Whole genome sequences of Salmonella enterica subspecies enterica serovar Typhi (S. Typhi) and Salmonella enterica subspecies enterica serovar Paratyphi A (S. Paratyphi A) from pediatric settings were used to assess the emerging Antimicrobial Resistance (AMR). The high throughput sequences of twenty pediatric clinical isolates of S. Typhi and S. Paratyphi A were retrieved and were screened for prevalent Antimicrobial Resistance Genes (ARGs) and Virulent Factors (VF). The resistance data was compared with the reference strains of S. Typhi and S. Paratyphi A. AMR studies identified sul1, sul2, dfrA7, tem-1, AH(6)-Id and APH(3″)-Ib as common ARGs. VFs were identified to understand the level of pathogenicity. The most prevalent AMR genes in the sequenced genomes were detected in phenotypically azithromycin-resistant S. Typhi. Correlation with the global genomes projected a trend of concurrent resistance to macrolides, ß lactams, fluoroquinolones (FQs), tetracyclines, ansamycins, and aminoglycosides. Traces of sulphonamide-resistance were observed indicating the emergence of a currently non-prevalent S. Typhi resistance that could be a future threat. Hence new antibiotic regimen to treat azithromycin-resistant S. Typhi should be formulated by avoiding the risks of aggravating sulphonamide resistance. The identified ARGs in genomes from paediatric isolates will aid future studies to design anti-bacterial compounds against S. Typhi and S. Paratyphi A.

Association Between Adult Antibiotic Use, Microbial Dysbiosis and Atopic Conditions - A Systematic Review.

Background: Strong associations between early antibiotic exposure and increased risk of childhood allergies have been established. Antibiotics have the potential to induce microbial dysbiosis that may be linked to allergic conditions. This review examines the limited available evidence on the associations between adult antibiotic use, microbial dysbiosis and atopic conditions. Methods: A systematic literature search was conducted using PubMed and Embase for relevant studies, published between 01-01-2000 and 08-17-2022. We searched for associations between antibiotic use, microbial dysbiosis, and allergic conditions in adults, defined as over 13 years of age for the purposes of this review. Results: Twenty-one studies were analyzed, with the inclusion of four narrative reviews as scarce relevant literature was found when stricter selection criteria were employed. Relevant studies predominantly focused on asthma. Significant microbial differences were observed in most measures between healthy subjects and subjects with allergic conditions. However, no system-wise and strain-wise associations were evident. Notably, at the phyla level, the Bacillota and Pseudomonadota phyla were associated with asthmatics, while the Actinobacteria phylum was linked to healthy controls. Asthmatics tends to reflect upregulation in the Bacillota and Pseudomonadota phyla in both airway and gut microbiomes. Conclusion: No compelling evidence could be found between adult antibiotic exposure, consequent microbial dysbiosis, and allergic conditions in adults. Our review is limited by scarce literature and therefore remains inconclusive. However, potential implications of antibiotic use impacting on allergic conditions justify additional research and heightened pharmacovigilance in this area.

Clinical features and risk factors for death in acute undifferentiated fever: A prospective observational study in rural community hospitals in six states of India.

BACKGROUND: Acute undifferentiated fever (AUF) ranges from self-limiting illness to life-threatening infections, such as sepsis, malaria, dengue, leptospirosis and rickettsioses. Similar clinical presentation challenges the clinical management. This study describes risk factors for death in patients hospitalized with AUF in India. METHODS: Patients aged ≥5 y admitted with fever for 2-14 d without localizing signs were included in a prospective observational study at seven hospitals in India during 2011-2012. Predictors identified by univariate analysis were analyzed by multivariate logistic regression for survival analysis. RESULTS: Mortality was 2.4% (37/1521) and 46.9% (15/32) died within 2 d. History of heart disease (p=0.013), steroid use (p=0.011), altered consciousness (p<0.0001), bleeding (p<0.0001), oliguria (p=0.020) and breathlessness (p=0.015) were predictors of death, as were reduced Glasgow coma score (p=0.005), low urinary output (p=0.004), abnormal breathing (p=0.006), abdominal tenderness (p=0.023), leucocytosis (p<0.0001) and thrombocytopenia (p=0.001) at admission. Etiology was identified in 48.6% (18/37) of fatal cases. CONCLUSIONS: Bleeding, cerebral dysfunction, respiratory failure and oliguria at admission, suggestive of severe organ failure secondary to systemic infection, were predictors of death. Almost half of the patients who died, died shortly after admission, which, together with organ failure, suggests that delay in hospitalization and, consequently, delayed treatment, contribute to death from AUF.