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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: 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]

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]

Background: Infant mortality has dropped considerably in India over the last 5 years. A sharp contrast to this decline in national average of infant mortality is the rate recorded during 2014-2015 from the southernmost district of Saiha, Mizoram having a common international border with Myanmar. As this district specific rate (113 per 1000 live births) is 3 times higher compared to the national and state average, the present investigation was carried out to identify associated factors.Methods: We examined secondary data made available by the national health mission, consulted with local community members and generated primary data through interviews. A case-control study design was followed. Mothers, who delivered a child during 2013-2015 and subsequently lost them due to infant death, formed the case group and controls were selected from same neighborhood as with case-mothers. The mother and child tracking system maintained by the district specific national health mission office was used for recruiting cases and controls. A total of 195 mothers were interviewed; 66 of them belonged to 'cases' and 129 were 'controls'.Results: The mean age of the respondents was 27 years (median 27; SD ± 5; minimum 17 & maximum 44). In uni-variate analyses 'child delivery at home', 'low birth weight', 'non-attendance of school by mothers', 'completed standard of school education by mothers', 'both parents working', 'mothers receiving blood transfusion during last pregnancy', and 'fourth or more birth order during last pregnancy' were associated with infant deaths. Intriguingly, the number of daily kuhva (raw areca nut) intake during last pregnancy was significantly higher among case-mothers compared to controls. In conditional logistic regression, 'low birth weight' (adjusted OR (AOR) 14.7; 95% CI 2.1-101.8; p = 0.006), and 'consumption of 4 or more kuhva per day' (AOR 8; 95% CI 1.9-34.3; p = 0.005) were independently associated with infant-death-experiences.Conclusion: The present investigation merits due attention from policy makers and health planners for immediate improvement in peri-natal and neonatal care services in the remote district of Saiha. Need for further research exploring socio-behavioural issues around areca nut consumption and effects of interventions to reduce areca nut intake on maternal and children health are underscored. [ABSTRACT FROM AUTHOR]

Background: In India, preventing mother-to-child transmission (PMTCT) of Human Immunodeficiency Virus (HIV) remains one of the foremost challenge in community health. Countrywide MTCT of HIV is estimated to be > 10,000 annually. Aims of present study are to find out the prevalence of HIV and correlates of HIV transmission among children given birth by HIV infected mother through systematic review along with meta-analysis.Methods: All avaiable articles are retrieved using MEDLINE, Cochrane Library, Science Direct, EMBASE, Google Scholar and PUBMED following guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) are applied to critically reviewing the selected articles. STATA 13.0 is used to preparation of forest plot for Meta-analysis. For assessment of heterogeneity and publication biases I2 statistics along with Begg and Mazumdar's test and Egger's tests are used. Odds ratio (OR) along with forest plots have been showing with 95% confidence interval (CI).Results: All together 10 studies including 1537 pairs of mothers and new births are assessed in present meta-analysis. Present analysis revealed the prevalence of HIV due to MTCT in India as 8.76% (95% CI; 5.76, 12.31). Analysis of subgroups exhibit a higher pooled prevalence in eastern region of India, 10.83% (95% CI: 5.9, 17.81) and lower in in Western region in India, 6.37% (95% CI: 4.65, 8.49). Status of MTCT before and after initiation of universal ART are 10.23% (95% CI 6.61, 14.55) and 7.93% (95% CI 4.18, 12.76) respectively. Associated factors with MTCT of HIV include absence of maternal prevention of MTCT intervention, OR = 10.82 (95% CI: 5.28, 22.17), lacking in administration of infant ARV (antiretroviral), OR = 8.21 (95% CI: 4.82, 14.0) and absence of medical facility during childbirth OR = 3.73 (95% CI: 1.67, 8.33).Conclusions: In India, pooled HIV prevalence of MTCT as high as 8.78% (95% CI; 5.76, 12.31) among babies born to infected mothers warrants urgent need of focused intervention for providing ART (PMTCT intervention), ensuring proper infant ARV prophylaxis, and avoiding delivery without proper medical facility to pregnant women with HIV for reduction of occurrence in HIV transmission from mothers to children. [ABSTRACT FROM AUTHOR]

Background: The blaNDM-1 (New Delhi Metallo-β-lactamase-1) gene has disseminated around the globe. NDM-1 producers are found to co-harbour resistance genes against many antimicrobials, including fluoroquinolones. The spread of large plasmids, carrying both blaNDM and plasmid-mediated fluoroquinolone resistance (PMQR) markers, is one of the main reasons for the failure of these essential antimicrobials. Methods: Enterobacteriaceae (n = 73) isolated from the blood of septicaemic neonates, admitted at a neonatal intensive care unit (NICU) in Kolkata, India, were identified followed by PFGE, antibiotic susceptibility testing and determination of MIC values for meropenem and ciprofloxacin. Metallo-β-lactamases and PMQRs were identified by PCR. NDM-positive isolates were studied for mutations in GyrA & ParC and for co-transmission of blaNDM and PMQR genes (aac(6′)-Ib-cr, qnrB, qnrS) through conjugation or transformation. Plasmid types, integrons, plasmid addiction systems, and genetic environment of the blaNDM gene in NDM-positive isolates and their transconjugants/ transformants were studied. Results: Isolated Enterobacteriaceae comprised of Klebsiella pneumoniae (n = 55), Escherichia coli (n = 16), Enterobacter cloacae (n = 1) and Enterobacter aerogenes (n = 1). The rates of ciprofloxacin (90%) and meropenem (49%) non-susceptibility were high. NDM was the only metallo-β-lactamase found in this study. NDM-1 was the predominant metallo-β-lactamase but NDM-5, NDM-7, and NDM-15 were also found. There was no significant difference in ciprofloxacin non-susceptibility (97% vs 85%) and the prevalence of PMQRs (85% vs 77%) between NDM-positive and NDM-negative isolates. Among the PMQRs, aac(6′)-Ib-cr was predominant followed by qnrB1 and qnrS1. Twenty-nine isolates (40%) co-harboured PMQRs and blaNDM, of which 12 co-transferred PMQRs along with blaNDM in large plasmids of IncFIIK, IncA/C, and IncN types. Eighty-two percent of NDM-positive isolates possessed GyrA and/or ParC mutations. Plasmids carrying only blaNDM were of IncHIB-M type predominantly. Most of the isolates had ISAba125 in the upstream region of the blaNDM gene. Conclusion: We hypothesize that the spread of PMQRs was independent of the spread of NDM-1 as their co-transfer was confirmed only in a few isolates. However, the co-occurrence of these genes poses a great threat to the treatment of neonates. [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., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The management of acute febrile illnesses places a heavy burden on clinical services in many low- and middle-income countries (LMICs). Bacterial and viral aetiologies of acute fevers are often clinically indistinguishable and, in the absence of diagnostic tests, the 'just-in-case' use of antibiotics by many health workers has become common practice, which has an impact on drug-resistant infections. Our study aims to answer the following question: in patients with undifferentiated febrile illness presenting to outpatient clinics/peripheral health centres in LMICs, can we demonstrate an improvement in clinical outcomes and reduce unnecessary antibiotic prescription over current practice by using a combination of simple, accurate diagnostic tests, clinical algorithms, and training and communication (intervention package)?, Methods: We designed a randomized, controlled clinical trial to evaluate the impact of our intervention package on clinical outcomes and antibiotic prescription rates in acute febrile illnesses. Available, point-of-care, pathogen-specific and non-pathogen specific (host markers), rapid diagnostic tests (RDTs) included in the intervention package were selected based on pre-defined criteria. Nine clinical study sites in six countries (Burkina Faso, Ghana, India, Myanmar, Nepal and Uganda), which represent heterogeneous outpatient care settings, were selected. We considered the expected seasonal variations in the incidence of acute febrile illnesses across all the sites by ensuring a recruitment period of 12 months. A master protocol was developed and adapted for country-specific ethical submissions. Diagnostic algorithms and choice of RDTs acknowledged current data on aetiologies of acute febrile illnesses in each country. We included a qualitative evaluation of drivers and/or deterrents of uptake of new diagnostics and antibiotic use for acute febrile illnesses. Sample size estimations were based on historical site data of antibiotic prescription practices for malarial and non-malarial acute fevers. Overall, 9 semi-independent studies will enrol a minimum of 21,876 patients and an aggregate data meta-analysis will be conducted on completion., Discussion: This study is expected to generate vital evidence needed to inform policy decisions on the role of rapid diagnostic tests in the clinical management of acute febrile illnesses, with a view to controlling the rise of antimicrobial resistance in LMICs., Trial Registration: Clinicaltrials.gov NCT04081051 . Registered on 6 September 2019. Protocol version 1.4 dated 20 December 2019.

Background: The bla NDM-1 (New Delhi Metallo-β-lactamase-1) gene has disseminated around the globe. NDM-1 producers are found to co-harbour resistance genes against many antimicrobials, including fluoroquinolones. The spread of large plasmids, carrying both bla NDM and plasmid-mediated fluoroquinolone resistance (PMQR) markers, is one of the main reasons for the failure of these essential antimicrobials., Methods: Enterobacteriaceae ( n  = 73) isolated from the blood of septicaemic neonates, admitted at a neonatal intensive care unit (NICU) in Kolkata, India, were identified followed by PFGE, antibiotic susceptibility testing and determination of MIC values for meropenem and ciprofloxacin. Metallo-β-lactamases and PMQRs were identified by PCR. NDM-positive isolates were studied for mutations in GyrA & ParC and for co-transmission of bla NDM and PMQR genes ( aac(6')-Ib-cr, qnrB, qnrS ) through conjugation or transformation. Plasmid types, integrons, plasmid addiction systems, and genetic environment of the bla NDM gene in NDM-positive isolates and their transconjugants/ transformants were studied., Results: Isolated Enterobacteriaceae comprised of Klebsiella pneumoniae ( n  = 55), Escherichia coli ( n  = 16), Enterobacter cloacae ( n  = 1) and Enterobacter aerogenes ( n  = 1). The rates of ciprofloxacin (90%) and meropenem (49%) non-susceptibility were high. NDM was the only metallo-β-lactamase found in this study. NDM-1 was the predominant metallo-β-lactamase but NDM-5, NDM-7, and NDM-15 were also found. There was no significant difference in ciprofloxacin non-susceptibility (97% vs 85%) and the prevalence of PMQRs (85% vs 77%) between NDM-positive and NDM-negative isolates. Among the PMQRs, aac(6')-Ib-cr was predominant followed by qnrB1 and qnrS1. Twenty-nine isolates (40%) co-harboured PMQRs and bla NDM , of which 12 co-transferred PMQRs along with bla NDM in large plasmids of IncFIIK, IncA/C, and IncN types. Eighty-two percent of NDM-positive isolates possessed GyrA and/or ParC mutations. Plasmids carrying only bla NDM were of IncHIB-M type predominantly. Most of the isolates had IS Aba125 in the upstream region of the bla NDM gene., Conclusion: We hypothesize that the spread of PMQRs was independent of the spread of NDM-1 as their co-transfer was confirmed only in a few isolates. However, the co-occurrence of these genes poses a great threat to the treatment of neonates., Competing Interests: The study protocol was carefully reviewed and approved by the Institutional Ethics Committee of the ICMR-National Institute of Cholera and Enteric Diseases (Indian Council of Medical Research) (No. A-1/2015-IEC, dated 31st August 2015).Not Applicable.The authors declare that they have no competing interest.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Salmonella Typhi is responsible for about 20 million episodes of illness and over 140,000 deaths annually globally. South Asia has the highest documented burden of typhoid and is home to the multi-drug resistant H58 strain that makes treatment more challenging. The WHO recommends the use of Typhoid Conjugate Vaccines in typhoid endemic countries. Decisions on the preferred immunization strategy should be based on an analysis of disease burden, availability, affordability, and operational feasibility. Typhoid vaccines have so far remained unimplemented as public health measures because of a perceived decline in typhoid burden in recent years. The apparent decline, based on hospital reports, may be a result of rampant antimicrobial use in the community and therefore estimation of disease incidence at the community is necessary to better measure disease incidence and transmission., Methods: Age-specific incidence of typhoid fever in children between 6 months and 15 years will be estimated in four community based cohorts in varied settings across India using standardized protocols for active fever surveillance in the community. Data will be collected on secured cloud infrastructure using a combination of android and web-based real-time data collection tools. Blood cultures will be done for children with fever lasting 3 or more consecutive days using automated blood culture systems. Those with blood-culture confirmed typhoid fever will be followed up till 90 days to estimate costs and clinical outcomes of the illness episodes. Environmental factors, access to safe water, sanitation, hygiene, food hygiene, demography, population density and socioeconomic status will be assessed periodically to characterise risk factors and permit extrapolation of burden to similar risk settings., Discussion: With the availability of licensed typhoid conjugated vaccines in India, it is important to consider whether the burden of disease is present and sufficient to require the use of vaccine in addition to other interventions. Active case finding in the community permits the detection of cases that would be missed in facility-based surveillance systems. Understanding the age distribution, burden, cost-of-illness and transmission of disease is essential to plan interventions and predict their potential impact., Trial Registration: The surveillance has been prospectively registered in the Clinical Trial Registry of India ( CTRI/2017/09/009719 ) on 12 September 2017.