Search

Introduction: Nosocomial infections caused by Multidrug Resistant (MDR) Pseudomonas aeruginosa (P. aeruginosa) have become a major clinical and public health concern. Moreover, the biofilm production protects the bacteria from antibiotics and thereby makes the drugs ineffective. Aim: To find out the β-lactamases profile of antimicrobial resistance and biofilm production of P. aeruginosa isolated from different clinical specimens of patients attending a tertiary care hospital of Kolkata, West Bengal, India. Materials and Methods: A total of 394 consecutive, nonduplicate isolates of P. aeruginosa were identified from 3559 Gram negative bacilli over a period of two years from July 2016 to June 2018. Identification of the isolates and antibiotic sensitivity testing was performed by using automated method and interpreted. Extended Spectrum β-Lactamases (ESBLs), Amp-C β-lactamase (AmpC) and Metallo-β-Lactamases (MBLs) were phenotypically detected by disk synergy test and MBLencoding genes were detected by multiplex Polymerase Chain Reaction (PCR). Biofilm production was done by tissue culture plate assay. Laboratory data and test results were statistically analysed in counts and percentages using MS Excel 2010 version. Results: Out of 394 strains of P. aeruginosa 288 (73.10%) were isolated from male patients whereas 106 (26.90%) were isolated from female patients. Maximum number of cases (67.26%) were from adult populations. The resistance pattern showed 72.33% resistance to ticarcillin-clavulanic acid followed by ciprofloxacin (53.80%), levofloxacin (50.25%), gentamicin (51.52%), ceftazidime (CAZ) (45.93%), cefoperazone-sulbactam (40.1%), aztreonam (34.77%), imipenem (33.5%), piperacillin/tazobactum (30.96%) and Meropenem (MRP) (29.18%). Out of 394 Pseudomonas spp isolates, 204 (51.77%) were MDR. Overall, ESBLs, AmpC and carbapenemase (MBL) production was detected in 145 (36.80%), 51 (12.94%) and 49 (12.43%) isolates by phenotypic methods. By genotypic method 53.34% were carbapenemase producing and blaNDM-1 (68.75%) was the most prevalent carbapenemase gene detected followed by blaVIM (18.75%) and co-production of blaNDM-1+ blaVIM was 12.5%. Biofilm production was observed in 158 (40.10%) isolates. Conclusion: Early detection of these ß-lactamases production is crucial not only for epidemiological study and effective infection control practices to limit the spread of infection but also for planning appropriate therapy according to the resistance mechanisms of the MDR strains. [ABSTRACT FROM AUTHOR]

Viral hepatitis is a hepatic disorder of public health importance. and it can be waterborne/foodborne or bloodborne[[1]]. Waterborne or foodborne hepatitis caused by hepatitis A virus (HAV) and hepatitis E virus (HEV), has faeco-oral route of transmission[[2]]. Diagnosis of HEV infection in immunocompromised patients and solid organ transplant recipients in whom seroconversion to anti-HEV antibodies is delayed or may not occur at all, is often challenging. Clinical course and duration of viremia in vertically transmitted hepatitis E virus (HEV) infection in babies born to HEV-infected mothers. [Extracted from the article]

• Gamma-valerolactone is a precursor for valuable chemicals and potential fuel additive. • Non-noble metals can be used in catalytic transfer hydrogenation (CTH) to produce GVL. • Dispersion of metal particles on catalysts influences hydrogenation efficiency. • Lewis acid and base sites are needed for obtaining high GVL yield and selectivity. • Metal leaching from catalysts is significant in aqueous conditions. The distinct physicochemical properties and renewable origin of gamma-valerolactone (GVL) have provided opportunities for diversifying its applications, particularly as a green solvent, excellent fuel additive, and precursor to valuable chemicals. Among the related publications found in the SCOPUS database (≈172 in the last 10 years), we focused our effort to review the conversion of levulinic acid (LA) to GVL over non-noble metal catalysts and the corresponding mechanisms (≈30 publications) as well as the applications of GVL as a solvent, fuel additive, and platform chemical (≈30 publications) mostly in the last five years (some preceding publications have also been included due to their relevance and importance in the field). The use of non-noble metals (e.g. , Cu and Zr) presents a greener route of GVL synthesis than the conventional practice employing noble metals (e.g. , Pd and Ru), in view of their higher abundance and milder reaction conditions needed (e.g. , low pressure and temperature without H 2 involved). The significance of the catalyst characteristics in promoting catalytic transfer hydrogenation of LA to GVL is critically discussed. Structural features and acid-base properties are found to influence the activity and selectivity of catalysts. Furthermore, metal leaching in the presence of water in catalytic systems is an important issue, resulting in catalyst deactivation. Various endeavors for developing catalysts using well-dispersed metal particles along with a combination of Lewis acid and base sites are suggested for efficiently synthesizing GVL from LA. [ABSTRACT FROM AUTHOR]

Background: Campylobacter is a well-known bacterial pathogen for triggering acute gastroenteritis in humans both in developed and developing countries. This organism is highly resistant to fluoroquinolones. Macrolides are very much useful for the treatment of campylobacteriosis when clinical therapy is necessary. However, increasing resistance to azithromycin, a potent macrolide has been reported in Campylobacter in recent years. Macrolide resistance in Campylobacter is found mainly due to point mutation in V region of 23S rRNA. Results: We have developed a PCR based assay, which can detect the azithromycin resistant and sensitive Campylobacter strains utilizing mutation responsible for the phenotype. This PCR was validated using 359 Campylobacter strains isolated from diarrhoeal patients at Kolkata, India. Antimicrobial resistance through disk diffusion method was also performed on these strains as a gold standard. Studies through sequencing analysis further confirmed the PCR result. Conclusion: This study describes a simple and rapid method for detection of mutation conferring macrolide resistance with additional feature of identification of sensitive strains. [ABSTRACT FROM AUTHOR]

Enteric fever, caused by Salmonella enterica, remains an unresolved public health problem in India and antimicrobial therapy is the main mode of treatment. The objective of this study was to characterize the Salmonella enterica isolates from Kolkata with respect to their antimicrobial resistance (AMR), virulence profiles and molecular subtypes. Salmonella enterica blood isolates were collected from clinically suspected enteric fever patients attending various hospitals in Kolkata, India from January 2009 to June 2013 and were tested for AMR profiles by standard protocols; for resistance gene transfer by conjugation; for resistance and virulence genes profiles by PCR; and for molecular subtypes by Pulsed Field Gel Electrophoresis (PFGE). A total of 77 Salmonella enterica serovar Typhi (S. Typhi) and 25 Salmonella enterica serovar Paratyphi A (S. Paratyphi A) from Kolkata were included in this study. Although multidrug resistance (resistance to chloramphenicol, ampicillin, co-trimoxazole) was decreasing in S. Typhi (18.2%) and absent in S. Paratyphi A, increased resistance to fluoroquinolone, the current drug of choice, caused growing concern for typhoid treatment. A single, non-conjugative non-IncHI1 plasmid of 180 kb was found in 71.4% multidrug resistant (MDR) S. Typhi; the remaining 28.6% isolates were without plasmid. Various AMR markers (blaTEM-1, catA, sul1, sul2, dfrA15, strA-strB) and class 1 integron with dfrA7 gene were detected in MDR S. Typhi by PCR and sequencing. Most of the study isolates were likely to be virulent due to the presence of virulence markers. Major diversity was not noticed among S. Typhi and S. Paratyphi A from Kolkata by PFGE. The observed association between AMR profiles and S. Typhi pulsotypes might be useful in controlling the spread of the organism by appropriate intervention. The study reiterated the importance of continuous monitoring of AMR and molecular subtypes of Salmonella isolates from endemic regions for better understanding of the disease epidemiology. [ABSTRACT FROM AUTHOR]

A resilient health system necessitates strong governance, political commitment, effective administrative entities and inter-organisational collaboration. This paper examines India's current health policy landscape and explores the analytical and operational capacities required to establish a robust post-pandemic health system using the policy capacity framework described by Wu et al. (2015). We emphasised the need for a coordinated policy response to strengthen health information systems, health service management, human resource management and healthcare financing. The role that the planned implementation of Indian public health management cadres would play in the coming era, the importance of a comprehensive health information management system and the need for operational coordination between government and non-governmental organisations has also been emphasised. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) is a major problem and an immediate alternative to antibiotics is the need of the hour. Research on the possible alternative products to tackle bacterial infections is ongoing worldwide. One of the most promising alternatives to antibiotics is the use of bacteriophages (phage) or phage-driven antibacterial drugs to cure bacterial infections caused by AMR bacteria. Phage-driven proteins, including holins, endolysins, and exopolysaccharides, have shown great potential in the development of antibacterial drugs. Likewise, phage virion proteins (PVPs) might also play an important role in the development of antibacterial drugs. Here, we have developed a machine learning-based prediction method to predict PVPs using phage protein sequences. We have employed well-known basic and ensemble machine learning methods with protein sequence composition features for the prediction of PVPs. We found that the gradient boosting classifier (GBC) method achieved the best accuracy of 80% on the training dataset and an accuracy of 83% on the independent dataset. The performance on the independent dataset is better than other existing methods. A user-friendly web server developed by us is freely available to all users for the prediction of PVPs from phage protein sequences. The web server might facilitate the large-scale prediction of PVPs and hypothesis-driven experimental study design. [ABSTRACT FROM AUTHOR]

The conversion of food waste and sludge into biogas via anaerobic digestion technology is gaining attention in recent years, which plays a significant role in waste valorization into bioenergy and promotes environmental sustainability. Biochar is a carbonaceous material produced via thermochemical conversion of biomass waste, and tailoring biochar for diverse environmental applications adheres to the principle of circular economy. The emerging application of biochar as an additive in the anaerobic digestion of food waste and sludge has been intensively investigated in the last few years. However, a comprehensive understanding of multifunctional roles of biochar and its mechanisms in the production of biogas via miscellaneous/complex anaerobic digestion process is yet to be attained. This review scrutinizes the key roles of biochar as an additive and emphasizes the influences of biochar characteristics on the anaerobic digestion processes and their capability to address the foremost challenges. This review also evaluates the techno-economic and environmental impacts of biochar synthesis and its emerging application for biogas production via anaerobic digestion to make the integrated process more economical and environmentally sustainable, and identifies challenges and prospects for future studies. [Display omitted] • Biochar manifests tunable physicochemical properties for diverse applications. • Biochar facilitates efficient anaerobic digestion (AD) of food waste and sludge. • Microbial functions and enzymatic activity can be enhanced by biochar addition. • A closed-loop material flow can be realized by integrating AD and pyrolysis. [ABSTRACT FROM AUTHOR]

Introduction: Hepatitis C virus (HCV) has posed a major public health problem globally. Since majority of HCV infected patients are asymptomatic, diagnosis of HCV infection is mainly based on the detection of anti-HCV antibodies by the Enzyme Linked Immunosorbent Assay (ELISA) or Rapid Diagnostic Tests (RDTs) and HCV Ribonucleic Acid (RNA) by real time Polymerase Chain Reaction (PCR) of serum or plasma samples. Aim: To assess the performance of RDT and 4th generation ELISA against real time reverse transcriptase PCR for the detection of HCV. Materials and Methods: A hospital-based cross-sectional study was carried out in the Virology Section, Department of Microbiology, Jawaharlal Nehru Institute of Medical Sciences (JNIMS), Imphal, Manipur, India, for a period of two years from June 2019 to May 2021. The study included 3,254 plasma samples from suspected cases of HCV monoinfection, and HCV/HIV co-infection. The plasma samples were subjected to anti-HCV antibodies by RDT (SD BIOLINE, South Korea) and 4th generation ELISA (Monolisa™ HCV Ag-Ab ULTRA, Bio-Rad, France), and HCV RNA by real time PCR. Data analysis was done using descriptive statistics, and performance of the assays was evaluated by using Cohen kappa test (1) and Receiver Operating Characteristic (ROC) curve. Results: PCR is considered as the gold standard test. HCV was detected by RDT in 453 (13.92%), ELISA in 413 (12.69%) and RT-PCR in 367 (11.28%) samples. The present study demonstrated sensitivity of 97.55% and specificity of 96.71% with Positive Predictive Value (PPV) of 79.03% by HCV-RDT. The 4th generation ELISA showed high sensitivity of 99.46% and specificity of 98.34%. Using ROC curve, the area under the curve was 81% for ELISA with diagnostic accuracy of 98.46%. Conclusion: 4th generation ELISA is more sensitive and specific than RDT for the detection of HCV infection. Confirmatory HCV-RNA assay could be performed to clear doubts related to false-positive and false-negative findings of the primary screening assays. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease-2019 (COVID-19) continues to pose serious challenges to healthcare systems globally with the disease progressing over time in crest-trough pattern of waves. We compared the patient characteristics and outcomes of critically ill patients admitted during the first and second waves of COVID-19 pandemic. Materials and Methods: We did a retrospective analysis of medical records of critically ill patients admitted to intensive care unit (ICU) at the peak period of both waves. The data on demographics, symptoms, treatment received, and outcomes of patients were recorded. Results: Compared to first wave, significantly more females, younger age group, and those without underlying comorbidities required ICU admission during the second wave. The treatments received during both periods were similar except for preferential use of methylprednisolone over dexamethasone and proclivity of bilevel positive airway pressure (BiPAP) ventilation over high-flow nasal cannula (HFNC). There was no significant difference in the duration of ICU stay and mortality of patients. During the first wave, the factors associated with nonsurvival of patients were advanced age, comorbidities, severe disease, and a lesser number of days on HFNC. All these factors along with higher Sequential Organ Failure Assessment (SOFA) score were observed to be linked with patient nonsurvival during the second wave. Conclusion: In India, the second wave of COVID-19 significantly influenced ICU demographics with a predominance of females and young adults requiring critical care. During both time periods, patients received similar treatment except for the propensity to use methylprednisolone and BiPAP as opposed to dexamethasone and HFNC in second wave. No significant difference in ICU mortality was noted. [ABSTRACT FROM AUTHOR]

Background: The primary aim of this study was to investigate the occurrence, characteristics, and antimicrobial resistance patterns of various Shigella serotypes isolated from patients with acute diarrhea of the Infectious Diseases Hospital in Kolkata from 2011–2019. Principal findings: During the study period, Shigella isolates were tested for their serotypes, antibiotic resistance pattern and virulence gene profiles. A total of 5.8% of Shigella spp. were isolated, among which S. flexneri (76.1%) was the highest, followed by S. sonnei (18.7%), S. boydii (3.4%), and S. dysenteriae (1.8%). Antimicrobial resistance against nalidixic acid was higher in almost all the Shigella isolates, while the resistance to β-lactamases, fluoroquinolones, tetracycline, and chloramphenicol diverged. The occurrence of multidrug resistance was found to be linked with various genes encoding drug-resistance, multiple mutations in the topoisomerase genes, and mobile genetic elements. All the isolates were positive for the invasion plasmid antigen H gene (ipaH). Dendrogram analysis of the plasmid and pulsed-field electrophoresis (PFGE) profiles revealed 70–80% clonal similarity among each Shigella serotype. Conclusion: This comprehensive long-term surveillance report highlights the clonal diversity of clinical Shigella strains circulating in Kolkata, India, and shows alarming resistance trends towards recommended antibiotics. The elucidation of this study's outcome is helpful not only in identifying emerging antimicrobial resistance patterns of Shigella spp. but also in developing treatment guidelines appropriate for this region. Author summary: Shigella spp. is one of the WHO-designated "antibiotic-resistant priority pathogens" that is the leading cause of bacterial diarrhea among children worldwide. The distribution of Shigella species varies depending on the geographic location, particularly in regions where environmental risk factors like substandard water quality, limited healthcare accessibility, and insufficient sanitation are widespread. The presence of serotype diversity and drug resistance combinations often leads to treatment failures. Therefore, it is crucial to comprehend the prevailing serogroups and antimicrobial resistance patterns of Shigella species in different geographical areas to implement effective treatment strategies. We have identified 535 Shigella positive cases from 9276 diarrheal cases. Multidrug-resistant (MDR) Shigella globally requires a profound understanding of its genetic diversity, as there is significant regional variation in MDR strains. In our study, we observed a broad spectrum of resistance among the Shigella strains, with over 53.6% of the isolates demonstrating multidrug resistance. Representative isolates were evaluated for antimicrobial resistance encoding and virulence-associated genes as they enact significantly in disease development and interaction with the host immune system. This report marks the initial presentation of the outcomes from long-term surveillance and molecular characterization of antimicrobial resistances in clinical Shigella strains in Kolkata since 2011. The outcome of this investigations will guide in identifying emerging antimicrobial resistance trend, formulating suitable treatment guidelines tailored to the community's needs, and establishing baseline data for comparison with potential outbreak strains in the future. [ABSTRACT FROM AUTHOR]

Background: Worldwide, noroviruses are the leading cause of acute gastroenteritis (AGE) in people of all age groups. In India, norovirus rates between 1.4 to 44.4% have been reported. Only a very few complete norovirus genome sequences from India have been reported. Objective: To perform full genome sequencing of noroviruses circulating in India during 2017–2021, identify circulating genotypes, assess evolution including detection of recombination events. Methodology: Forty-five archived norovirus-positive samples collected between October 2017 to July 2021 from patients with AGE from two hospitals in Kolkata, India were processed for full genome sequencing. Phylogenetic analysis, recombination breakpoint analysis and comprehensive mutation analysis were also performed. Results: Full genome analysis of norovirus sequences revealed that strains belonging to genogroup (G)I were genotyped as GI.3[P13]. Among the different norovirus capsid-polymerase combinations, GII.3[P16], GII.4 Sydney[P16], GII.4 Sydney[P31], GII.13[P16], GII.16[P16] and GII.17 were identified. Phylogenetic analysis confirmed phylogenetic relatedness with previously reported norovirus strains and all viruses were analyzed by Simplot. GII[P16] viruses with multiple residue mutations within the non-structural region were detected among circulating GII.4 and GII.3 strains. Comprehensive mutation analysis and selection pressure analysis of GII[P16] viruses showed positive as well as negative selection sites. A GII.17 strain (NICED-BCH-11889) had an untypeable polymerase type, closely related to GII[P38]. Conclusion: This study highlights the circulation of diverse norovirus strains in eastern India. These findings are important for understanding norovirus epidemiology in India and may have implications for future vaccine development. [ABSTRACT FROM AUTHOR]

Background Oral cholera vaccine (OCV) and incremental improvements in household water, sanitation, and hygiene (WASH) within cholera-endemic areas can reduce cholera risk. However, we lack empiric evaluation of their combined impact. Methods We evaluated a cluster-randomized, placebo-controlled trial of OCV (Shanchol) in Kolkata, India. The study population included 108 777 individuals, and 106 879 nonpregnant individuals >1 year of age were eligible to receive 2 doses of OCV or placebo. We measured cholera risk in all household members assigned to OCV vs placebo and in all members of households with "Better" vs "Not Better" WASH, where WASH was classified according to validated criteria. Protection was measured by Cox proportional hazard models. Results Residence in an OCV household was associated with protective effectiveness (PE) of 54% (95% CI, 42%–64%; P <.001) and was similar regardless of Better (PE, 57%; 95% CI, 26%–75%; P =.002) or Not Better (PE, 53%; 95% CI, 40%–64%; P <.001) household WASH. Better WASH household residence was associated with PE of 30% (95% CI, 5%–48%; P =.023) and was similar in OCV (PE, 24%; 95% CI, −26% to 54%; P =.293) and placebo (PE, 29%; 95% CI, −3% to 51%; P =.069) households. When assessed conjointly, residence in OCV households with Better WASH was associated with the greatest PE against cholera at 69% (95% CI, 49%–81%; P <.001). Conclusions These findings suggest that the combination of a vaccine policy and improved WASH reduces cholera risk more than either would alone, although the magnitude of either intervention was not affected by the other. Future randomized trials investigating OCV and WASH interventions separately and together are recommended to further understand the interaction between OCV and WASH. [ABSTRACT FROM AUTHOR]

Understanding the genetic dynamics of circulating Human Adenovirus (HAdV) types is pivotal for effectively managing outbreaks and devising targeted interventions. During the West Bengal outbreak of 2022–2023, an investigation into the genetic characteristics and outbreak potential of circulating HAdV types was conducted. Twenty-four randomly selected samples underwent whole-genome sequencing. Analysis revealed a prevalent recombinant strain, merging type 3 and type 7 of human mastadenovirus B1 (HAd-B1) species, indicating the emergence of recent strains of species B in India. Furthermore, distinctions in VA-RNAs and the E3 region suggested that current circulating strains of human mastadenovirus B1 (HAd-B1) possess the capacity to evade host immunity, endure longer within hosts, and cause severe respiratory infections. This study underscores the significance of evaluating the complete genome sequence of HAdV isolates to glean insights into their outbreak potential and the severity of associated illnesses. [ABSTRACT FROM AUTHOR]

Recurrent Tuberculosis patients contribute to a significant proportion of TB burden in India. A nationwide survey was conducted during 2019–2021 across India among adults to estimate the prevalence of TB. A total of 322480 individuals were screened and 1402 were having TB. Of this, 381 (27.1%) had recurrent TB. The crude prevalence (95% CI) of recurrent TB was 118 (107–131) per 100,000 population. The median duration between episodes of TB was 24 months. The proportion of drug resistant TB was 11.3% and 3.6% in the recurrent group and new TB patients respectively. Higher prevalence of recurrent TB was observed in elderly, males, malnourished, known diabetics, smokers, and alcohol users. (p<0.001). To prevent TB recurrence, all treated tuberculosis patients must be followed at least for 24 months, with screening for Chest X-ray, liquid culture every 6 months, smoking cessation, alcohol cessation, nutritional interventions and good diabetic management. [ABSTRACT FROM AUTHOR]

Background: The burden of the COVID-19 pandemic on healthcare systems worldwide has been compromising the progress made in the fight against HIV. This paper aims to determine how the COVID-19 pandemic has impacted HIV comprehensive care service delivery globally as well as to consolidate the evidence and recommendations that may be useful in averting future crisis. Methods: This review adheres to PRISMA guidelines. PubMed, DOAJ, Science Direct and other sources like Google Scholar and citations from included studies were searched methodically to locate studies evaluating the effects of COVID on services for HIV care. The NIH and JBI quality assessment tools were used for the quality assessment of individual studies. Results: In the present review 31 eligible studies were included and the impact on HIV care cascade were summarised under six themes: Lab services, Treatment and allied services, Counselling services, Outreach services, Psycho-social impact and Implementation of sustainable strategies. The studies also presented many innovative alternatives which were lucidly highlighted in the present article. Conclusion: Current evidence depicts multiple factors are responsible for the interruption of HIV care service delivery during the pandemic, especially in low resources settings. The prospective, alternative solutions that have been used to circumvent the threat have also been addressed in this review, in addition to the negative aspects that have been observed. Transition with new innovative, sustainable care paradigms may prove to be the building blocks in removing HIV-AIDS as a public health threat. Registration: Open Science Framework (DOI: 10.17605/OSF.IO/74GHM). [ABSTRACT FROM AUTHOR]

Background: Salmonella enterica serotype Typhi is one of the major pathogens causing typhoid fever and a public health burden worldwide. Recently, the increasing number of multidrug-resistant strains of Salmonella spp. has made this utmost necessary to consider bacteriophages as a potential alternative to antibiotics for S. Typhi infection treatment. Salmonella phage STWB21, isolated from environmental water, has earlier been reported to be effective as a safe biocontrol agent by our group. In this study, we evaluated the efficacy of phage STWB21 in reducing the burden of salmonellosis in a mammalian host by inhibiting Salmonella Typhi invasion into the liver and spleen tissue. Results: Phage treatment significantly improved the survival percentage of infected mice. This study also demonstrated that oral administration of phage treatment could be beneficial in both preventive and therapeutic treatment of salmonellosis caused by S. Typhi. Altogether the result showed that the phage treatment could control tissue inflammation in mice before and after Salmonella infection. Conclusions: To the best of our knowledge, this is the first report of phage therapy in a mouse model against a clinically isolated Salmonella Typhi strain that includes direct visualization of histopathology and ultrathin section microscopy images from the liver and spleen sections. [ABSTRACT FROM AUTHOR]

Background Global cholera control efforts rely heavily on effective water, sanitation, and hygiene (WASH) interventions in cholera-endemic settings. Methods Using data from a large, randomized controlled trial of oral cholera vaccine conducted in Kolkata, India, we evaluated whether natural variations in WASH in an urban slum setting were predictive of cholera risk. From the control population (n = 55 086), baseline WASH data from a randomly selected "training subpopulation" (n = 27 634) were analyzed with recursive partitioning to develop a dichotomous ("better" vs "not better") composite household WASH variable from several WASH features collected at baseline, and this composite variable was then evaluated in a mutually exclusive "validation population" (n = 27 452). We then evaluated whether residents of better WASH households in the entire population (n = 55 086) experienced lower cholera risk using Cox regression models. Better WASH was defined by a combination of 4 dichotomized WASH characteristics including safe source of water for daily use, safe source of drinking water, private or shared flush toilet use, and always handwashing with soap after defecation. Results Residence in better WASH households was associated with a 30% reduction in risk of cholera over a 5-year period (adjusted hazard ratio, 0.70 [95% confidence interval,.49–.99]; P =.048). We also found that the impact of better WASH households on reducing cholera risk was greatest in young children (0–4 years) and this effect progressively declined with age. Conclusions The evidence suggests that modest improvements in WASH facilities and behaviors significantly modify cholera risk and may be an important component of cholera prevention and elimination strategies in endemic settings. Clinical Trials Registration. NCT00289224. [ABSTRACT FROM AUTHOR]

Background: Metagenomic analysis of the gut microbiome and resistome is instrumental for understanding the dynamics of diarrheal pathogenesis and antimicrobial resistance transmission (AMR). Metagenomic sequencing of 20 diarrheal fecal samples from Kolkata was conducted to understand the core and variable gut microbiota. Five of these samples were used for resistome analysis. The pilot study was conducted to determine a microbiota signature and the source of antimicrobial resistance genes (ARGs) in the diarrheal gut. Results: 16S rRNA amplicon sequencing was performed using Illumina MiSeq platform and analysed using the MGnify pipeline. The Genome Taxonomy Database (GTDB-Tk) was used for bacterial taxonomic identification. Diarrheal etiology was determined by culture method. Phylum Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria were consistently present in 20 samples. Firmicutes was the most abundant phylum in 11 samples. The Bacteroidetes/Firmicutes ratio was less than 1 in 18 samples. 584 genera were observed. 18 of these were present in all the 20 samples. Proteobacteria was the dominant phylum in 6 samples associated with Vibrio cholerae infection. Conservation of operational taxonomic units (OTUs) among all the samples indicated the existence of a core microbiome. Asymptomatic carriage of pathogens like Vibrio cholerae and Helicobacter pylori was found. Signature of Candidate phyla or "microbial dark matter" occurred. Significant correlation of relative abundance of bacterial families of commensals and pathogens were found. Whole-genome sequencing (WGS) on Illumina MiSeq system and assembly of raw reads using metaSPAdes v3.9.1 was performed to study the resistome of 5 samples. ABRicate was used to assign ARG function. 491 resistance determinants were identified. In 80% of the samples tetracycline resistance was the most abundant resistance determinant. High abundance of ARGs against β-lactams, aminoglycosides, quinolones and macrolides was found. Eschericia sp. was the major contributor of ARGs. Conclusions: This is the first comparative study of the gut microbiome associated with different diarrheal pathogens. It presents the first catalogue of different bacterial taxa representing the core and variable microbiome in acute diarrheal patients. The study helped to define a trend in the gut microbiota signature associated with diarrhea and revealed which ARGs are abundantly present and the metagenome-assembled genomes (MAGs) contributing to AMR. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus) has constantly been evolving into different forms throughout its spread in the population. Emerging SARS-CoV-2 variants, predominantly the variants of concern (VOCs), could have an impact on the virus spread, pathogenicity, and diagnosis. The recently emerged "Omicron" variant has exhibited rapid transmission and divergence. The spike protein of SARS-CoV-2 has consistently been appearing as the mutational hotspot of all these VOCs. In order to determine a deeper understanding of the recently emerged and extremely divergent "Omicron", a study of amino acid usage patterns and their substitution patterns was performed and compared with those of the other four successful variants of concern ("Alpha", "Beta", "Gamma", and "Delta"). We observed that the amino acid usage of "Omicron" has a distinct pattern that distinguishes it from other VOCs and is significantly correlated with the increased hydrophobicity in spike proteins. We observed an increase in the non-synonymous substitution rate compared with the other four VOCs. Considering the phylogenetic relationship, we hypothesized about the functional interdependence between recombination and the mutation rate that might have resulted in a shift in the optimum of the mutation rate for the evolution of the "Omicron" variant. The results suggest that for improved disease prevention and control, more attention should be given to the significant genetic differentiation and diversity of newly emerging variants. [ABSTRACT FROM AUTHOR]

Background: In the Bengal Delta, research has shown that climate and cholera are linked. One demonstration of this is the relationship between interannual ocean-atmospheric oscillations such as the El Niño Southern Oscillation (ENSO) and the Indian Ocean Dipole (IOD). What remains unclear in the present literature is the nature of this relationship in the specific context of Kolkata, and how this relationship may have changed over time. Results: In this study, we analyse the changing relationship between ENSO and IOD with cholera in Kolkata over recent (1999–2019) and historical (1897–1941) time intervals. Wavelet coherence analysis revealed significant non-stationary association at 2–4 year and 4–8 year periods between cholera and both interannual timeseries during both time intervals. However, coherence was notably weakened in the recent interval, particularly with regards to ENSO, a result supported by a complementary SARIMA analysis. Similar coherence patterns with temperature indicate it could be an important mediating factor in the relationship between cholera and oscillating climate phenomena in Kolkata. Conclusions: This study reveals a shifting relationship between cholera and climate variables (ENSO and IOD) in Kolkata, suggesting a decoupling between environmental influences and cholera transmission in recent years. Our results therefore do not suggest that an intensification of ENSO is likely to significantly influence cholera in the region. We also find that the relationship between cholera and interannual climate variables is distinct to Kolkata, highlighting the spatial heterogeneity of the climate-cholera relationship even within the Bengal Delta. [ABSTRACT FROM AUTHOR]

Background: Cholera in Kolkata remains endemic and the Indian city is burdened with a high number of annual cases. Climate change is widely considered to exacerbate cholera, however the precise relationship between climate and cholera is highly heterogeneous in space and considerable variation can be observed even within the Indian subcontinent. To date, relatively few studies have been conducted regarding the influence of climate on cholera in Kolkata. Methods: We considered 21 years of confirmed cholera cases from the Infectious Disease Hospital in Kolkata during the period of 1999–2019. We used Generalised Additive Modelling (GAM) to extract the non-linear relationship between cholera and different climatic factors; temperature, rainfall and sea surface temperature (SST). Peak associated lag times were identified using cross-correlation lag analysis. Results: Our findings revealed a bi-annual pattern of cholera cases with two peaks coinciding with the increase in temperature in summer and the onset of monsoon rains. Variables selected as explanatory variables in the GAM model were temperature and rainfall. Temperature was the only significant factor associated with summer cholera (mean temperature of 30.3 °C associated with RR of 3.8) while rainfall was found to be the main driver of monsoon cholera (550 mm total monthly rainfall associated with RR of 3.38). Lag time analysis revealed that the association between temperature and cholera cases in the summer had a longer peak lag time compared to that between rainfall and cholera during the monsoon. We propose several mechanisms by which these relationships are mediated. Conclusions: Kolkata exhibits a dual-peak phenomenon with independent mediating factors. We suggest that the summer peak is due to increased bacterial concentration in urban water bodies, while the monsoon peak is driven by contaminated flood waters. Our results underscore the potential utility of preventative strategies tailored to these seasonal and climatic patterns, including efforts to reduce direct contact with urban water bodies in summer and to protect residents from flood waters during monsoon. [ABSTRACT FROM AUTHOR]

Background: HCV infection is very common in multi-transfused β-thalassemia patients who need regular blood transfusions. Aim: The study was conducted to determine the epidemiology of HCV in multi-transfused β-thalassemia patients in West Bengal, India. Methods: Over a span of six years, blood samples were collected from HCV sero-reactive β-thalassemia patients and processed for viral RNA isolation followed by nested RT-PCR for qualitative viremia detection. The HCV genotype was determined by amplifying the partial HCV core gene by nested RT-PCR followed by DNA sequencing and NCBI genotyping tools. Phylogenetic and phylogeographic studies were performed with MEGA-X and BEAST software, respectively. Results: Out of 917 multi-transfused HCV sero-reactive β-thalassemia patients, 598 (65.21%) were HCV RNA positive while 250 (41.80%) had spontaneously cleared the virus. A significant percentage of male patients from rural areas (p = 0.042) and economically backward class (p = 0.002) were at higher risk of HCV infection. Female thalassemia patients and individuals belonging to ages 11–15 years had higher chances of spontaneous clearance. The most prevalent circulatory HCV genotype was 3a (78.26%) followed by 1b (12.04%). Phylogeographic analyses revealed that the 3a strains share genomic similarities with strains from Pakistan, Sri Lanka, and Thailand, whereas the 1b strains share similarities with strains from Thailand, Vietnam, Russia, and China. Uncommon HCV subtypes 3g and 3i were also detected. Conclusion: The high prevalence of HCV infection among β-thalassemia patients of West Bengal, India indicates NAT-based assays should be implemented for HCV screening in donor blood to eliminate HCV by 2030. [ABSTRACT FROM AUTHOR]

Cyclospora cayetanensis, a recently described coccidian parasite causes severe gastroenteric disease worldwide. Limited studies are found on the incidence of C. cayetanensis infection from India; hence remains largely unknown. To date, no case of cyclosporiasis from eastern India has been reported. In this study, we described an incidental case of C. cayetanensis in a 30 years old Bengali female patient with no travel history from eastern India. In June 2022, the patient presented with a history of diarrhoea persisting for more than two months with continuous passage foul smelling stools for which she took multiple antibiotics that were ineffective. There were no Salmonella, Shigella, or Vibrio-like organisms in the patient's faecal sample, and Toxin A/B of Clostridium difficile was also not detected by ELISA. The patient was HIV-negative. Finally, UV autofluorescence and DNA-based diagnosis confirmed the presence of C. cayetanensis, and the treatment with a combination of appropriate antibiotics was successful. This case report could raise awareness about C. cayetanensis associated diarrhoeal cases in India. [ABSTRACT FROM AUTHOR]

Background: Importance of the amphizoic amoeba Entamoeba moshkovskii is increasing in the study of amoebiasis as a common human pathogen in some settings. Limited studies are found on the genetic and phylogenetic characterization of E. moshkovskii from India; hence remain largely unknown. In this study, we determined the prevalence and characterized the E. moshkovskii isolates in eastern India. Methods: A three-year systemic surveillance study among a total of 6051 diarrhoeal patients from ID Hospital and BC Roy Hospital, Kolkata was conducted for E. moshkovskii detection via a nested PCR system targeting 18S rRNA locus. The outer primer set detected the genus Entamoeba and the inner primer pair identified the E. moshkovskii species. The 18S rRNA locus of the positive samples was sequenced. Genetic and phylogenetic structures were determined using DnaSP.v5 and MEGA-X. GraphPad Prism (v.8.4.2), CA, USA was used to analyze the statistical data. Result: 4.84% (95%CI = 0.0433–0.0541) samples were positive for Entamoeba spp and 3.12% (95%CI = 0.027–0.036) were infected with E. moshkovskii. E. moshkovskii infection was significantly associated with age groups (X2 = 26.01, P<0.0001) but not with gender (Fisher's exact test = 0.2548, P<0.05). A unique seasonal pattern was found for E. moshkovskii infection. Additionally, 46.56% (95%CI = 0.396–0.537) were sole E. moshkovskii infections and significantly associated with diarrheal incidence (X2 = 335.5,df = 9; P<0.0001). Sequencing revealed that the local E. moshkovskii strains were 99.59%-100% identical to the prototype (GenBank: KP722605.1). The study found certain SNPs that showed a correlation with clinical features, but it is not necessarily indicative of direct control over pathogenicity. However, SNPs in the 18S rRNA gene could impact the biology of the amoeba and serve as a useful phylogenetic marker for identifying pathogenic E. moshkovskii isolates. Neutrality tests of different coinfected subgroups indicated deviations from neutrality and implied population expansion after a bottleneck event or a selective sweep and/or purifying selection in co-infected subgroups. The majority of FST values of different coinfected subgroups were <0.25, indicating low to moderate genetic differentiation within the subgroups of this geographical area. Conclusion: The findings reveal the epidemiological significance of E. moshkovskii infection in Eastern India as the first report in this geographical area and expose this species as a possible emerging enteric pathogen in India. Our findings provide useful knowledge for further research and the development of future control strategies against E. moshkovskii. Author summary: Although Entamoeba genus consists of many different species, not all are pathogenic. Entamoeba histolytica is the only species recognized as a definite pathogen associated with intestinal and extraintestinal infections. Nowadays, the importance of other morphologically identical Entamoeba species, like amphizoic E. moshkovskii is increasing, as it has been reported in human patients over the years from different countries. Investigations into the pathogenic potential of E. moshkovskii are ongoing, and only limited studies have been conducted on genetic characterization from India. This study reveals the epidemiology and population structure of E. moshkovskii in diarrhoeal patients from eastern India. Our study showed that the prevalence of E. moshkovskii in diarrhoeal patients is higher than E. histolytica in the studied region. In addition, there was a unique seasonal pattern, found for the infection. The high prevalence rate of sole infection in patients suggests that it is one of the definite etiological agents for diarrhoeal disease in eastern India. The further study identified two SNPs in the 18S rRNA locus, significantly associated with the sole infection cases and hence they can be regarded as a marker for identifying pathogenic isolates of E. moshkovskii. Many novel genotypes were obtained in the study indicating high genetic diversity in E. moshkovskii population conferring adaptability in a changing environment. Further research is needed to ensure proper control measures for this infection for better health care. [ABSTRACT FROM AUTHOR]

So much genomic similarities yet causing different diseases, is like a paradox in Salmonella biology. Repeat is one of the probes that can explain such differences. Here, a comparative genomics approach is followed to identify and characterize repeats that might play role in adaptation and pathogenesis. Repeats are non-randomly distributed in the genomes except few typhoid causing strains. Perfect long repeats are rare compare to polymorphic ones and both are statistically consistent. Significant differences in repeat densities in stress related genes manifest its probable participation in survival and virulence. 573 and 1053 repeat loci have been identified which are exclusively associated with stress and virulent genes respectively. In Salmonella Typhi, an octameric VNTR locus is found in between acrD and yffB genes having more than 25 perfect copies across Salmonella Typhi but possesses only single copy in other serovars. This repeat can be used as a diagnostic probe for typhoid. [ABSTRACT FROM AUTHOR]

The gut microbiome derived short chain fatty acids perform multitude of functions to maintain gut homeostasis. Here we studied how butyrate stymie enteric bacterial invasion in cell using a simplistic binary model. The surface of the mammalian cells is enriched with microdomains rich in cholesterol that are known as rafts and act as entry points for pathogens. We showed that sodium butyrate treated RAW264.7 cells displayed reduced membrane cholesterol and less cholera-toxin B binding coupled with increased membrane fluidity compared to untreated cells indicating that reduced membrane cholesterol caused disruption of lipid rafts. The implication of such cellular biophysical changes on the invasion of enteric pathogenic bacteria was assessed. Our study showed, in comparison to untreated cells, butyrate-treated cells significantly reduced the invasion of Shigella and Salmonella, and these effects were found to be reversed by liposomal cholesterol treatment, increasing the likelihood that the rafts' function against bacterial invasion. The credence of ex vivo studies found to be in concordance in butyrate fed mouse model as evident from the significant drift towards a protective phenotype against virulent enteric pathogen invasion as compared to untreated mice. To produce a cytokine balance towards anti-inflammation, butyrate-treated mice produced more of the gut tissue anti-inflammatory cytokine IL-10 and less of the pro-inflammatory cytokines TNF-α, IL-6, and IFN-γ. In histological studies of Shigella infected gut revealed a startling observation where number of neutrophils infiltration was noted which was correlated with the pathology and was essentially reversed by butyrate treatment. Our results ratchet up a new dimension of our understanding how butyrate imparts resistance to pathogen invasion in the gut. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori is a key agent for causing gastric complications linked with gastric disorders. In response to infection, host cells stimulate autophagy to maintain cellular homeostasis. However, H. pylori have evolved the ability to usurp the host's autophagic machinery. High mobility group box1 (HMGB1), an alarmin molecule is a regulator of autophagy and its expression is augmented during infection and gastric cancer. Therefore, this study aims to explore the role of glycyrrhizin (a known inhibitor of HMGB1) in autophagy during H. pylori infection. Main methods: Human gastric cancer (AGS) cells were infected with the H. pylori SS1 strain and further treatment was done with glycyrrhizin. Western blot was used to examine the expression of autophagy proteins. Autophagy and lysosomal activity were monitored by fluorescence assays. A knockdown of HMGB1 was performed to verify the effect of glycyrrhizin. H. pylori infection in in vivo mice model was established and the effect of glycyrrhizin treatment was studied. Results: The autophagy-lysosomal pathway was impaired due to an increase in lysosomal membrane permeabilization during H. pylori infection in AGS cells. Subsequently, glycyrrhizin treatment restored the lysosomal membrane integrity. The recovered lysosomal function enhanced autolysosome formation and concomitantly attenuated the intracellular H. pylori growth by eliminating the pathogenic niche. Additionally, glycyrrhizin treatment inhibited inflammation and improved gastric tissue damage in mice. Conclusion: This study showed that inhibiting HMGB1 restored lysosomal activity to ameliorate H. pylori infection. It also demonstrated the potential of glycyrrhizin as an antibacterial agent to address the problem of antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Background: Sexually transmitted infections (STIs) are one of the leading causes of health, and economic burdens in the developing world, leading to considerable morbidity, mortality, and stigma. The incidence and prevalence of the four curable STIs viz. syphilis, gonorrhoea, chlamydia, and trichomoniasis vary remarkably across different geographical locations. In India, the prevalence of four curable STI among general populations is in between 0 to 3.9 percent. However, it is assumed that STI prevalence is much higher among subpopulations practicing high-risk behaviour. Like men who have sex with men (MSM), transgender (TG), injecting drug users (IDU), and female sex workers (FSW). Objectives: In the present circumstances, a systematic review is necessary to integrate the available data from previously published peer-reviewed articles and published reports from several competent authorities to provide the prevalence and geographical distribution of the four curable STIs among the key population of India. Methods: All available articles will be retrieved from PubMed, Google Scholar, Cochrane database, Scopus, Science Direct, and the Global Health network using the appropriate search terms. The data will be extracted through data extraction form as per PICOS (population, intervention, comparison, outcome, study design) framework. Risk of bias and quality assessment will be performed according to the situation with the help of available conventional protocol. Discussion: The future systematic review, generated from the present protocol, may provide evidence of the prevalence and geographical distribution of the four curable STIs among the key population of India. We hope that the findings of the future systematic review will strengthen the existing surveillance system in India, to determine the above-mention STIs prevalence among key populations in India. Protocol registration number: International Prospective Register for Systematic Reviews (PROSPERO) number CRD42022346470. [ABSTRACT FROM AUTHOR]

Background: Eradication of Helicobacter pylori provides the most effective treatment for gastroduodenal diseases caused by H. pylori infection. Clarithromycin, a member of the macrolide family, still remains the most important antibiotic used in H. pylori eradication treatment. But the increasing prevalence of clarithromycin resistant H. pylori strains due to point mutations in the V region of the 23S rRNA, poses a great threat in treating the ailing patients. So, we aimed for PCR-mediated rapid detection of the point mutation at 2143 position of 23S rRNA gene in H. pylori that is relevant to clarithromycin resistance from culture and simultaneously from biopsy specimens to avoid the empirical treatment. Results: Newly developed PCR assay using DNA of pure culture detected point mutation in 23S rRNA gene in 21 (8.04%) of 261 clinical strains tested. The agar dilution method showed that all these 21 strains were resistant to clarithromycin indicating the perfect match of the PCR based results. Additionally, the sequencing study also identified the A to G mutation at 2143 position in 23S rRNA gene of the resistant strains only. Consequently, the newly developed Nested-ASP-PCR dealing directly with 50 biopsy specimens demonstrated 100% sensitivity and specificity with the findings of agar dilution method taken as Gold standard. Bioinformatics based analysis such as accessibility analysis and dot plot clearly stated that the base pairing probability has increased due to mutation. Computational studies revealed that the point mutation confers more stability in secondary structure due to conversion of loop to stem. Furthermore, interaction studies showed binding affinity of the CLR to the mutant type is weaker than that to the wild type. Conclusion: This assay outlines a rapid, sensitive and simple approach to identify point mutation that confers clarithromycin resistance as well as clarithromycin sensitive strains, providing rapid initiation of effective antibiotic treatment. Additionally, it is simple to adopt for hospital based diagnostic laboratories to evaluate the degree of regional clarithromycin resistance from biopsy specimens itself. Furthermore, in silico studies provide evidence or a signal that the prevalence of clarithromycin resistance may rise in the near future as a result of this point mutation. [ABSTRACT FROM AUTHOR]

In 2015, the swine derived A(H1N1)pdm09 pandemic strain outbreak became widespread throughout the different states of India. The reported cases and deaths in 2015 surpassed the previous years with more than 39000 laboratory confirmed cases and a death toll of more than 2500 people. There are relatively limited complete genetic sequences available for this virus from Asian countries. In this study, we describe the full genome analysis of influenza 2015 A(H1N1)pdm09 viruses isolated from West Bengal between January through December 2015. The phylogenetic analysis of the haemagglutinin sequence revealed clustering with globally circulating strains of genogroup 6B. This was further confirmed by the constructed concatenated tree using all eight complete gene segments of Kolkata A(H1N1)pdm09 isolates with the other strains from different timeline and lineages. A study from Massachusetts Institute of Technology (MIT) in 2015 reported novel mutations T200A and D225N in haemagglutinin gene of a 2014 Indian strain (A/India/6427/2014). However, in all the pandemic strains of 2014–2015 reported from India, so far including A(H1N1)pdm09 strains from Kolkata, D225N mutation was not observed, though the T200A mutation was found to be conserved. Neuraminidase gene of the analyzed strains did not show any oseltamivir resistant mutation H275Y suggesting continuation of Tamiflu® as drug of choice. The amino acid sequences of the all gene segments from 2015 A(H1N1)pdm09 isolates identified several new mutations compared to the 2009 A(H1N1)pdm09 strains, which may have contributed towards enhanced virulence, compared to 2009 A(H1N1)pdm09 strains. [ABSTRACT FROM AUTHOR]

We examined the stools of 23 patients in Kolkata, who were diagnosed as cholera patients because Vibrio cholerae O1 was detected from their stools by culturing methods, and further explored by metagenomic sequencing analysis. Subsequently, the presence of the gene encoding A subunit of cholera toxin (ctxA) and the cholera toxin (CT) level in these stool samples were examined. ctxA was examined by both metagenomic sequencing analysis and polymerase chain reaction. In these examinations, two samples did not show positive in any of these tests. The metagenomic analysis showed that the genes for Streptococcus pneumoniae and Salmonella enterica were present in the stools of these two patients, respectively. Therefore, these two patients were not considered to have diarrhea due to V. cholerae infection. From these results, we predicted that some Kolkata residents harbor a small number of V. cholerae in their intestines as a form of subclinical infection with V. cholerae. Next, we analyzed the stool samples of 22 diarrhea patients from which V. cholerae was not isolated. The results showed that 3 of the patients seemed to have subclinical infection of V. cholerae based on the amount of the genes. These results indicated that subclinical infections with V. cholerae O1 occur in Kolkata. [ABSTRACT FROM AUTHOR]

Background & objectives: Regional Virus Research and Diagnostic Laboratory established at ICMRNational Institute of Cholera and Enteric Diseases (NICED) regularly receives samples for dengue screening and serotyping from patients of acute febrile illness (AFI) from Kolkata and adjacent districts. In this study, data over a three year period (August 2016-July 2019) was retrospectively analyzed to provide insight into the epidemiological trends of dengue fever in this region. Methods: Serological screening of dengue was performed by detection of NS1 antigen and/or immunoglobulin M (IgM) antibody. Dengue serotyping was done by conventional or real-time reverse transcriptase–PCR. The data were analyzed to describe the distribution of dengue with respect to age of patient, duration of fever on the day of blood collection and month of the year. Zip codes were used for spatial plotting. Results: Out of the 24,474 samples received from Kolkata and its adjacent districts (Hooghly, Howrah, North and South 24 Parganas), 38.3 per cent (95% confidence interval: 37.7-38.9%) samples were screened positive for dengue. The correlation between age and dengue positivity was found to be weak. A combination of dengue NS1 antigen and dengue IgM antibody detection may be a better option for detecting dengue positivity compared to a single test. Most AFI cases were tested from August to November during the study period, with maximum dengue positivity noted during September (45.9%). The predominant serotype of 2016, dengue virus serotype 1 (DENV-1), was almost entirely replaced by DENV-2 in 2017 and 2018. Interpretation & conclusions: Dengue continues to be an important cause of AFI in the region and roundthe- year preventive measures are required for its control. Serotype switching is alarming and should be monitored routinely. [ABSTRACT FROM AUTHOR]

Aim: To develop an accurate lab score based on in-hospital patients' potent clinical and biological parameters for predicting COVID-19 patient severity during hospital admission. Methods: To conduct this retrospective analysis, a derivation cohort was constructed by including all the available biological and clinical parameters of 355 COVID positive patients (recovered = 285, deceased = 70), collected in November 2020-September 2021. For identifying potent biomarkers and clinical parameters to determine hospital admitted patient severity or mortality, the receiver operating characteristics (ROC) curve and Fischer's test analysis was performed. Relative risk regression was estimated to develop laboratory scores for each clinical and routine biological parameter. Lab score was further validated by ROC curve analysis of the validation cohort which was built with 50 COVID positive hospital patients, admitted during October 2021-January 2022. Results: Sensitivity vs. 1-specificity ROC curve (>0.7 Area Under the Curve, 95% CI) and univariate analysis (p<0.0001) of the derivation cohort identified five routine biomarkers (neutrophil, lymphocytes, neutrophil: lymphocytes, WBC count, ferritin) and three clinical parameters (patient age, pre-existing comorbidities, admitted with pneumonia) for the novel lab score development. Depending on the relative risk (p values and 95% CI) these clinical parameters were scored and attributed to both the derivation cohort (n = 355) and the validation cohort (n = 50). ROC curve analysis estimated the Area Under the Curve (AUC) of the derivation and validation cohort which was 0.914 (0.883–0.945, 95% CI) and 0.873 (0.778–0.969, 95% CI) respectively. Conclusion: The development of proper lab scores, based on patients' clinical parameters and routine biomarkers, would help physicians to predict patient risk at the time of their hospital admission and may improve hospital-admitted COVID-19 patients' survivability. [ABSTRACT FROM AUTHOR]

Background: The Joint United Nations Programme on AIDS (UNAIDS) has emphasized on the incidence-prevalence ratio (IPR) and incidence-mortality ratio (IMR) to measure the progress in HIV epidemic control. In this paper, we describe the status of epidemic control in India and in various states in terms of UNAIDS's recommended metrices. Method: The National AIDS Control Programme (NACP) of India spearheads work on mathematical modelling to estimate HIV burden based on periodically conducted sentinel surveillance for providing guidance to program implementation and policymaking. Using the results of the latest round of HIV Estimations in 2019, IPR and IMR were calculated. Results: National level IPR was 0.029 [0.022–0.037] in 2019 and ranged from 0.01 to 0.15 in various States and Union Territories (UTs). Corresponding Incidence-Mortality Ratio was at 0.881 [0.754–1.014] nationally and ranged between 0.20 and 12.90 across the States/UTs. Conclusions: Based on UNAIDS recommended indicators for HIV epidemic control, namely IPR and IMR; national AIDS response in India appears on track. However, the program success is not uniform and significant heterogeneity as well as expanding epidemic was observed at the level of States or UTs. Reinforcing States/UTs specific and focused HIV prevention, testing and treatment initiatives may help in the attainment of 2030 Sustainable Development Goals of ending AIDS as a public health threat by 2030. [ABSTRACT FROM AUTHOR]

In addition to the ongoing global problem of healthcare-acquired infections, the COVID-19 pandemic continues to pose a serious threat to the health of the global population. This unprecedented pandemic situation has reinforced the need for the development of technologies that can curb the transmission of viruses among human beings and help to control the infection. Existing disinfection techniques using either ultraviolet light or harsh chemicals pose safety risks and are not suitable for use in the presence of humans. Thus, the need for a safe and effective disinfection technique that can be used in the presence of humans to control viral transmission is evident. A technique that can continuously disinfect air and surfaces in indoor environments, where the chances of viral transmission are high, can be an indispensable tool to fight such a pandemic. The Airlens Minus Corona (AMC) device provided by Persapien Innovations has been developed to achieve this goal. In this study, the antiviral functionality and biocompatibility of AMC were evaluated. Activated water mist (AWM) generated from this device was tested in vitro and in vivo for its toxicity to cell lines and in animal model. The AWM was found to be non-cytotoxic to L-929 cell lines and had no sign of clinical toxicity in an animal model (rabbit). This device was further used to inactivate animal viruses and bacteriophages. The AWM was found to be effective in the complete inactivation of influenza A H1N1 virus within 5 minutes of direct treatment. This device was also found to be effective in inactivating >90% of bacteriophage particles. [ABSTRACT FROM AUTHOR]

Understanding the global burden of enterotoxigenic E. coli (ETEC) and Shigella diarrhea as well as estimating the cost effectiveness of vaccines to control these two significant pathogens have been hindered by the lack of a diagnostic test that is rapid, simple, sensitive, and can be applied to the endemic countries. We previously developed a simple and rapid assay, Rapid Loop mediated isothermal amplification based Diagnostic Test (RLDT) for the detection of ETEC and Shigella spp. (Shigella). In this study, the RLDT assay was evaluated in comparison with quantitative PCR (qPCR), culture and conventional PCR for the detection of ETEC and Shigella. This validation was performed using previously collected stool samples from endemic countries, from the travelers to the endemic countries, as well as samples from a controlled human infection model study of ETEC. The performance of RLDT from dried stool spots was also validated. RLDT resulted in excellent sensitivity and specificity compared to qPCR (99% and 99.2% respectively) ranging from 92.3 to 100% for the individual toxin genes of ETEC and 100% for Shigella. Culture was less sensitive compared to RLDT. No significant differences were noted in the performance of RLDT using samples from various sources or stool samples from moderate to severe diarrhea or asymptomatic infections. RLDT performed equally well in detection of ETEC and Shigella from the dried stool samples on filter papers. This study established that RLDT is sufficiently sensitive and specific to be used as a simple and rapid diagnostic assay to detect ETEC and Shigella in endemic countries to determine disease burden of these pathogens in the national and subnational levels. This information will be important to guide public health and policy makers to prioritize resources for accelerating the development and introduction of effective preventative and/or treatment interventions against these enteric infections. Author summary: Enterotoxigenic E. coli (ETEC) and Shigella spp (Shigella) causes significant global morbidity and mortality, especially in low-and middle-income countries (LMICs). Since culture methods to detect Shigella are not sensitive, and the methods used to detect ETEC have not been feasible outside of specialized, well-equipped laboratories, the true burden of these pathogens at national and sub-national levels are mostly not available. Morbidity and mortality estimates, for these two pathogens are crucial to assess their relative public health importance in LMICs. We developed a simple and rapid diagnostic assay called the RLDT (Rapid Loop-mediated isothermal amplification based Diagnostic Test) for detection of ETEC and Shigella. In this study we evaluated RLDT compared to other currently available assays using previously collected stool samples. Our data showed that the RLDT assay exhibited high sensitivity and specificity for detection of ETEC and Shigella, with its result available within 50 minutes. The sensitivity of RLDT was higher than culture for these pathogens. We conclude that RLDT could be used as a rapid and simple diagnostic test to determine the burden of ETEC and Shigella in LMICs as well as in clinical vaccine trials of these pathogens. [ABSTRACT FROM AUTHOR]

• Vibriosis is an important public health issue in South Asia. • In South Asia, cases of vibriosis are underdiagnosed and underreported. • The isolation rate of vibriosis-causing species in South Asia is estimated to be 4%. • Vibriosis should be considered in gastroenteritis differential diagnosis. South Asia remains home to foodborne diseases caused by the Vibrio species. We aimed to compile and update information on the epidemiology of vibriosis in South Asia. For this systematic review and meta-analysis, we searched PubMed, Web of Science, EMBASE, and Google Scholar for studies related to vibriosis in South Asia published up to May 2023. A random-effects meta-analysis was used to estimate the pooled isolation rate of non–cholera-causing Vibrio species. In total, 38 studies were included. Seven of these were case reports and 22 were included in the meta-analysis. The reported vibriosis cases were caused by non-O1/non-O139 V. cholerae, V. parahaemolyticus, V. fluvialis , and V. vulnificus. The overall pooled isolation rate was 4.0% (95% confidence interval [CI] 3.0-5.0%) in patients with diarrhea. Heterogeneity was high (I2 = 98.0%). The isolation rate of non-O1/non-O139 V. cholerae, V. parahaemolyticus , and V. fluvialis were 9.0 (95% CI 7.0-10.0%), 1.0 (95% CI 1.0-2.0%), and 2.0 (95% CI: 1.0-3.0%), respectively. Regarding V. parahaemolyticus , O3:K6 was the most frequently isolated serotype. Cases peaked during summer. Several studies reported antibiotic-resistant strains and those harboring extended-spectrum beta-lactamases genes. This study demonstrates a high burden of infections caused by non–cholera-causing Vibrio species in South Asia. [ABSTRACT FROM AUTHOR]

In addition to the ongoing global problem of healthcare-acquired infections, the COVID-19 pandemic continues to pose a serious threat to the health of the global population. This unprecedented pandemic situation has reinforced the need for the development of technologies that can curb the transmission of viruses among human beings and help to control the infection. Existing disinfection techniques using either ultraviolet light or harsh chemicals pose safety risks and are not suitable for use in the presence of humans. Thus, the need for a safe and effective disinfection technique that can be used in the presence of humans to control viral transmission is evident. A technique that can continuously disinfect air and surfaces in indoor environments, where the chances of viral transmission are high, can be an indispensable tool to fight such a pandemic. The Airlens Minus Corona (AMC) device provided by Persapien Innovations has been developed to achieve this goal. In this study, the antiviral functionality and biocompatibility of AMC were evaluated. Activated water mist (AWM) generated from this device was tested in vitro and in vivo for its toxicity to cell lines and in animal model. The AWM was found to be non-cytotoxic to L-929 cell lines and had no sign of clinical toxicity in an animal model (rabbit). This device was further used to inactivate animal viruses and bacteriophages. The AWM was found to be effective in the complete inactivation of influenza A H1N1 virus within 5 minutes of direct treatment. This device was also found to be effective in inactivating >90% of bacteriophage particles. [ABSTRACT FROM AUTHOR]

Viruses are intracellular pathogens and are dependent on host cellular resources to carry out their cycles of perpetuation. Obtaining an integrative view of host–virus interaction is of utmost importance to understand the complex and dynamic interplay between viral components and host machineries. Besides its obvious scholarly significance, a comprehensive host–virus interaction profile also provides a platform where from host determinants of pro-viral and antiviral importance can be identified and further be subjected to therapeutic intervention. Therefore, adjunct to conventional methods of prophylactic vaccination and virus-directed antivirals, this host-targeted antiviral approach holds promising therapeutic potential. In this review, we present a comprehensive landscape of host cellular reprogramming in response to infection with rotavirus (RV) which causes profuse watery diarrhea in neonates and infants. In addition, an emphasis is given on how host determinants are either usurped or subverted by RV in course of infection and how therapeutic manipulation of specific host factors can effectively modulate the RV life cycle. [ABSTRACT FROM AUTHOR]

The aging population is of growing concern all across the globe as well as in India. Polypharmacy has been defined as the simultaneous use of multiple medications by an individual and the clinical suitability of such use. Polypharmacy is found more frequently in the geriatric population. Researches in India have also reiterated the fact. Polypharmacy in the geriatric population leads to many negative consequences such as increased adverse drug reactions, falls, frailty, and even increased mortality. Moreover, it leads to increased out-of-pocket expenditure. Polypharmacy also poses risk of poor treatment adherence and missed dose in the geriatric population. Mitigation measures in this regard may include increased awareness among physicians, improved medication management and adherence, efforts to reduce self-medication, and improper crosspathy. [ABSTRACT FROM AUTHOR]

Background: Cholera, an acute diarrheal disease is a major public health problem in many developing countries. Several rapid diagnostic tests (RDT) are available for the detection of cholera, but their efficacies are not compared in an endemic setting. In this study, we have compared the specificity and sensitivity of three RDT kits for the detection of Vibrio cholerae O1 and compared their efficiency with culture and polymerase chain reaction (PCR) methods. Methods: Five hundred six diarrheal stool samples collected from patients from two different hospitals in Kolkata, India were tested using SD Bioline Cholera, SMART-II Cholera O1 and Crystal-VC RDT kits. All the stool samples were screened for the presence of V. cholerae by direct and enrichment culture methods. Stool DNA-based PCR assay was made to target the cholera toxin (ctxAB) and O1 somatic antigen (rfb) encoding genes. Statistical evaluation of the RDTs has been made using STATA software with stool culture and PCR results as the gold standards. The Bayesian latent class model (LCM) was used to evaluate the diagnostic tests in the absence of the gold standard. Results: Involving culture technique as gold standard, the sensitivity and specificity of the cholera RDT kits in the direct testing of stools was highest with SAMRT-II (86.1%) and SD-Cholera (94.4%), respectively. The DNA based PCR assays gave very high sensitivity (98.4%) but the specificity was comparatively low (75.3%). After enrichment, the high sensitivity and specificity was detected with SAMRT-II (78.8%) and SD-Cholera (99.1%), respectively. Considering PCR as the gold standard, the sensitivity and specificity of the RDTs remained between 52.3–58.2% and 92.3–96.8%, respectively. In the LCM, the sensitivity of direct and enrichment testing was high in SAMRT-II (88% and 92%, respectively), but the specificity was high in SD cholera for both the methods (97% and 100%, respectively). The sensitivity/specificity of RDTs and direct culture have also been analyzed considering the age, gender and diarrheal disease severity of the patients. Conclusion: Overall, the performance of the RDT kits remained almost similar in terms of specificity and sensitivity. Performance of PCR was superior to the antibody-based RDTs. The RTDs are very useful in identifying cholera cases during outbreak/epidemic situations and for making them as a point-of-care (POC) testing tool needs more improvement. Author summary: Cholera is caused by toxigenic Vibrio cholerae, which induces massive fluid accumulation in the host's gut and secretory diarrhea. Cholera deaths can be prevented by timely diagnosis and early treatment of the patients using rehydration therapy. Outbreaks of cholera are often reported in several countries due to poor quality of drinking water and lack of sanitation. Early diagnosis of cholera outbreaks is highly useful for the enforcement of control measures. In many cholera endemic countries, laboratory resources in detecting the cholera cases are limited. Even though the conventional culture methods of the isolation and identification V. cholerae are useful for cholera diagnosis, its sensitivity is not superior compared to antibody and DNA-based techniques. Several antibody-based cholera rapid diagnostic kits (RTDs) are designed for use as a point-of-care (POC) device or field conditions. Using the diarrheal stool samples, we compared the performance of three cholera RDTs with bacterial culture and PCR assays. Applying culture and PCR results as the gold standards and also in the absence of a gold standard, appropriate statistical analysis has been made for diagnostic test evaluations. We have also considered the presence of other pathogens in the stools and clinical characteristics of the patients in the analysis. Though the cholera RDT kits highly useful for the detection of V. cholerae O1, even in the presence of other pathogens in the stools, they cannot be considered as a POC tool due to lack of required specificity. [ABSTRACT FROM AUTHOR]

Increased human–animal interfaces impose threats on human life by creating scope for the emergence and resurgence of many infectious diseases. Over the last two decades, emergence of novel viral diseases such as SARS, influenza A/H1N1(09) pdm; MERS; Nipah virus disease; Ebola haemorrhagic fever and the current COVID-19 has resulted in massive outbreaks, epidemics and pandemics thereby causing profound losses of human life, health and economy. The current COVID-19 pandemic has affected more than 200 countries, reporting a global case load of 167,878,000 with 2 per cent mortality as on May 26, 2021. This has highlighted the importance of reducing human– animal interfaces to prevent such zoonoses. Rapid deforestation, shrinking of boundaries between human and animal, crisis for natural habitation, increasing demands for wildlife products and threat of extinction compounded by biodiversity narrowing compel to increased human–animal conflict and contact. Large quantities of animal waste generated due to animal agriculture may also allow rapid selection, amplification, dissemination of zoonotic pathogens and facilitate zoonotic pathogen adaptation and hinder host evolution for resistance. Public health system faces challenges to contain such epidemics due to inadequate understanding, poor preparedness, lack of interdisciplinary approach in surveillance and control strategy and deficient political commitments. Because the management measures are beyond the purview of health system alone, policy-level adaptation in the transdisciplinary issues are required, emphasizing the engagement of multiple stakeholders towards wildlife protection, alternative land use, community empowerment for natural resource management and regulation on business of wildlife products to ensure comprehensive one health practice. [ABSTRACT FROM AUTHOR]

Background: Despite established benefits, exclusive breastfeeding (EBF) rate remains poor in India. This study measured the rate of early initiation of breastfeeding and EBF up to 42 days postpartum period and the reasons associated with early interruption of it. Methods: In this study we followed a cohort 319 mother-newborn dyads, on a scheduled day of each week for six postpartum weeks (42 postpartum days), during May 2017 – March 2019. We used standard maternal 24 h recall method to collect data on newborn feeding practices. Additionally, using content the analysis method, we analysed the data captured through open ended question on current breastfeeding practice and reasons to identify the sociocultural facilitators/barriers of exclusive breastfeeding. Results: Of the retained 306 newborns, early initiation of breastfeeding rate was 60% (184/306), whereas, EBF rate was 47% (143/306). Mothers' educational level did not emerge as a risk for unsuccessful breastfeeding practices, whereas, father being not the major earner of the family (Relative risk [RR] 2.4; 95% Confidence interval [CI] 1.7,3.3), mothers who did not believe that effect of breastfeeding is longstanding (RR 1.8; 95% CI 1.3, 2.1) emerged as a risk for unsuccessful EBF practices. Lack of self-conviction about EBF among mothers; significant family members' influence; cultural beliefs; emerged as major socio-environmental barriers of early interruption of exclusive breastfeeding. Repeated counselling by the healthcare provider particularly focusing on exclusive breastfeeding, supportive family environment in terms of the elders being aware of the positive health outcomes of it, and prior positive experience emerged as the socio-environmental facilitators for successful EBF until 42 postpartum days. Conclusions: We conclude that the socio-environmental causes need to be addressed through the present healthcare delivery system for ensuring better infant feeding outcome. [ABSTRACT FROM AUTHOR]

Viruses are intracellular pathogens and are dependent on host cellular resources to carry out their cycles of perpetuation. Obtaining an integrative view of host-virus interaction is of utmost importance to understand the complex and dynamic interplay between viral components and host machineries. Besides its obvious scholarly significance, a comprehensive host-virus interaction profile also provides a platform where from host determinants of pro-viral and antiviral importance can be identified and further be subjected to therapeutic intervention. Therefore, adjunct to conventional methods of prophylactic vaccination and virus-directed antivirals, this host-targeted antiviral approach holds promising therapeutic potential. In this review, we present a comprehensive landscape of host cellular reprogramming in response to infection with rotavirus (RV) which causes profuse watery diarrhea in neonates and infants. In addition, an emphasis is given on how host determinants are either usurped or subverted by RV in course of infection and how therapeutic manipulation of specific host factors can effectively modulate the RV life cycle. [ABSTRACT FROM AUTHOR]

Bacterial species are hosts to horizontally acquired mobile genetic elements (MGEs), which encode virulence, toxin, antimicrobial resistance, and other metabolic functions. The bipartite genome of Vibrio cholerae harbors sporadic and conserved MGEs that contribute in the disease development and survival of the pathogens. For a comprehensive understanding of dynamics of MGEs in the bacterial genome, we engineered the genome of V. cholerae and examined in vitro and in vivo stability of genomic islands (GIs), integrative conjugative elements (ICEs), and prophages. Recombinant vectors carrying the integration module of these GIs, ICE and CTXΦ, helped us to understand the efficiency of integrations of MGEs in the V. cholerae chromosome. We have deleted more than 250 acquired genes from 6 different loci in the V. cholerae chromosome and showed contribution of CTX prophage in the essentiality of SOS response master regulator LexA, which is otherwise not essential for viability in other bacteria, including Escherichia coli. In addition, we observed that the core genome-encoded RecA helps CTXΦ to bypass V. cholerae immunity and allow it to replicate in the host bacterium in the presence of similar prophage in the chromosome. Finally, our proteomics analysis reveals the importance of MGEs in modulating the levels of cellular proteome. This study engineered the genome of V. cholerae to remove all of the GIs, ICEs, and prophages and revealed important interactions between core and acquired genomes. [ABSTRACT FROM AUTHOR]