Publications by authors named "Carl Britto"

22 Publications

  • Page 1 of 1

Neonatal and infant mortality associated with spina bifida: A systematic review and meta-analysis.

PLoS One 2021 12;16(5):e0250098. Epub 2021 May 12.

National Perinatal Epidemiology Unit (NPEU), Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.

Objectives: A systematic review was conducted in high-income country settings to analyse: (i) spina bifida neonatal and IMRs over time, and (ii) clinical and socio-demographic factors associated with mortality in the first year after birth in infants affected by spina bifida.

Data Sources: PubMed, Embase, Ovid, Web of Science, CINAHL, Scopus and the Cochrane Library were searched from 1st January, 1990 to 31st August, 2020 to review evidence.

Study Selection: Population-based studies that provided data for spina bifida infant mortality and case fatality according to clinical and socio-demographical characteristics were included. Studies were excluded if they were conducted solely in tertiary centres. Spina bifida occulta or syndromal spina bifida were excluded where possible.

Data Extraction And Synthesis: Independent reviewers extracted data and assessed their quality using MOOSE guideline. Pooled mortality estimates were calculated using random-effects (+/- fixed effects) models meta-analyses. Heterogeneity between studies was assessed using the Cochrane Q test and I2 statistics. Meta-regression was performed to examine the impact of year of birth cohort on spina bifida infant mortality.

Results: Twenty studies met the full inclusion criteria with a total study population of over 30 million liveborn infants and approximately 12,000 spina bifida-affected infants. Significant declines in spina bifida associated infant and neonatal mortality rates (e.g. 4.76% decrease in IMR per 100, 000 live births per year) and case fatality (e.g. 2.70% decrease in infant case fatality per year) were consistently observed over time. Preterm birth (RR 4.45; 2.30-8.60) and low birthweight (RR 4.77; 2.67-8.55) are the strongest risk factors associated with increased spina bifida infant case fatality.

Significance: Significant declines in spina bifida associated infant/neonatal mortality and case fatality were consistently observed, advances in treatment and mandatory folic acid food fortification both likely play an important role. Particular attention is warranted from clinicians caring for preterm and low birthweight babies affected by spina bifida.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250098PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115829PMC
May 2021

Reducing rates of discharge against medical advice in the neonatal intensive care unit in a tertiary care hospital in South India: a mixed-methods study.

Trop Med Int Health 2021 Mar 29. Epub 2021 Mar 29.

Department of Neonatology, St. John's Medical College, Bangalore, India.

Objective: To elucidate characteristics among neonates and their mothers who were discharged against medical advice (DAMA), providers' perspectives on DAMA and the effect of an intervention to reduce DAMA in a tertiary care hospital in South India.

Methods: We conducted a mixed-methods study to identify neonates at risk of DAMA. We reviewed charts of neonates and their mothers who were DAMA and conducted logit regression analysis to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI) to determine associations with DAMA. We conducted focus group discussions with nurses and doctors. We developed an intervention that included family counselling, supplemental funds for hospital bills and involving family members to reduce DAMA.

Results: Of 10 834 neonates, 179 (1.7%) were DAMA over the study period. Maternal characteristics associated with DAMA included higher previous parity (aOR 1.9, 95% CI 1.1-2.3, P = 0.001). Mothers who received antenatal care had lower odds of DAMA (aOR 0.2, 95% CI 0.1-0.7, P = 0.039). Neonates with lower birth weight (aOR 2.1, 95% CI 1.7-9.4, P = 0.002) and congenital malformations (aOR 3.3, 95% CI 1.1-5.3, P = 0.005) also had higher odds of DAMA. The most commonly cited reasons for DAMA were financial constraints, inadequate counselling and perceived poor prognosis. The average monthly number of neonates who were DAMA decreased from 3.6 (1.6%) to 1.5 (0.6%) after our multi-pronged intervention.

Conclusions: Neonates with severe illness and poor prognosis had higher odds of DAMA. A multi-pronged intervention demonstrated reductions in the rates of DAMA. This intervention may be trialled in similar settings to reduce DAMA.
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http://dx.doi.org/10.1111/tmi.13578DOI Listing
March 2021

Typhoid and paratyphoid fever: a clinical seminar.

J Travel Med 2021 04;28(3)

Department of Infectious Diseases, Christian Medical College, Vellore, India.

Rationale for review: Enteric fever (EF) caused by Salmonella enterica subspecies enterica serovar Typhi (Salmonella Typhi) and S. Paratyphi (Salmonella Paratyphi) remains an important cause of infectious morbidity and mortality in many low-income countries and, therefore, still poses a major infectious risk for travellers to endemic countries. Main findings: Although the global burden of EF has decreased over the past two decades, prevalence of EF remains high in Asia and Africa, with the highest prevalence reported from the Indian subcontinent. These statistics are mirrored by data on travel-related EF. Widespread and increasing antimicrobial resistance has narrowed treatment options for travel-related EF. Ceftriaxone- and azithromycin-based therapies are commonly used, even with the emergence of extremely drug-resistant typhoid in Pakistan. Preventive measures among locals and travellers include provision of safe food and water and vaccination. Food and water precautions offer limited protection, and the efficacy of Salmonella Typhi vaccines is only moderate signifying the need for travellers to be extra cautious. Recommendations: Improvement in the diagnosis of typhoid with high degree of clinical suspicion, better diagnostic assays, early and accurate detection of resistance, therapy with appropriate drugs, improvements in hygiene and sanitation with provision of safe drinking water in endemic areas and vaccination among travellers as well as in the endemic population are keys to controlling typhoid. While typhoid vaccines are recommended for travellers to high-risk areas, moderate efficacy and inability to protect against Salmonella Paratyphi are limitations to bear in mind. Improved Salmonella Typhi vaccines and vaccines against Salmonella Paratyphi A are required.
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http://dx.doi.org/10.1093/jtm/taab012DOI Listing
April 2021

Comparing COVID-19 vaccine allocation strategies in India: A mathematical modelling study.

Int J Infect Dis 2021 Feb 31;103:431-438. Epub 2020 Dec 31.

Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA; Division of Infectious Disease, St. John's Research Institute, Bengaluru, India. Electronic address:

Background: The development and widespread use of an effective SARS-CoV-2 vaccine could prevent substantial morbidity and mortality associated with COVID-19 and mitigate the secondary effects associated with non-pharmaceutical interventions.

Methods: We used an age-structured, expanded SEIR model with social contact matrices to assess age-specific vaccine allocation strategies in India. We used state-specific age structures and disease transmission coefficients estimated from confirmed incident cases of COVID-19 between 1 July and 31 August 2020. Simulations were used to investigate the relative reduction in mortality and morbidity of vaccine allocation strategies based on prioritizing different age groups, and the interactions of these strategies with concurrent non-pharmaceutical interventions. Given the uncertainty associated with COVID-19 vaccine development, we varied vaccine characteristics in the modelling simulations.

Results: Prioritizing COVID-19 vaccine allocation for older populations (i.e., >60 years) led to the greatest relative reduction in deaths, regardless of vaccine efficacy, control measures, rollout speed, or immunity dynamics. Preferential vaccination of this group often produced relatively higher total symptomatic infections and more pronounced estimates of peak incidence than other assessed strategies. Vaccine efficacy, immunity type, target coverage, and rollout speed significantly influenced overall strategy effectiveness, with the time taken to reach target coverage significantly affecting the relative mortality benefit comparative to no vaccination.

Conclusions: Our findings support global recommendations to prioritize COVID-19 vaccine allocation for older age groups. Relative differences between allocation strategies were reduced as the speed of vaccine rollout was increased. Optimal vaccine allocation strategies will depend on vaccine characteristics, strength of concurrent non-pharmaceutical interventions, and region-specific goals.
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http://dx.doi.org/10.1016/j.ijid.2020.12.075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834611PMC
February 2021

Pathogen genomic surveillance of typhoidal infection in adults and children reveals no association between clinical outcomes and infecting genotypes.

Trop Med Health 2020 13;48:58. Epub 2020 Jul 13.

Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, OX3 7LE UK.

Background: India is endemic for enteric fever, and it is not known whether the variations in clinical manifestations between patients are due to host, environmental or pathogen factors.Blood culture surveillance was conducted at St. John's Medical College Hospital, Bangalore, between July 2016 and June 2017. Clinical, laboratory and demographic data were collected from each case, and bacterial isolates were subjected to whole genome sequencing. Comparative analysis between adults and paediatric patients was carried out to ascertain differences between adult and paediatric disease.

Results: Among the 113 cases of blood culture-confirmed enteric fever, young adults (16-30 years) and children < 15 years accounted for 47% and 37% of cases, respectively. Anaemia on presentation was seen in 46% of cases, and 19% had an abnormal leucocyte count on presentation. The majority received treatment as inpatients (70%), and among these, adults had a significantly longer duration of admission when compared with children ( = 0.002). There were atypical presentations including arthritis, acute haemolysis and a case of repeated typhoid infection with two separate Typhi genotypes. There was no association between infecting genotype/serovar and treatment status (outpatient vs inpatient), month of isolation, duration of admission, patient age (adult or child), antimicrobial susceptibility, Widal positivity or haematologic parameters.

Conclusions: Amidst the many public health concerns of South India, enteric fever continues to contribute substantially to hospital burden with non-specific as well as uncommon clinical features in both paediatric and adult populations likely driven by host and environmental factors. Robust clinical surveillance as well monitoring of pathogen population structure is required to inform treatment and preventive strategies.
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http://dx.doi.org/10.1186/s41182-020-00247-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359007PMC
July 2020

Persistent circulation of a fluoroquinolone-resistant Salmonella enterica Typhi clone in the Indian subcontinent.

J Antimicrob Chemother 2020 02;75(2):337-341

Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, OX3 7LE, UK.

Background: The molecular structure of circulating enteric fever pathogens was studied using hospital-based genomic surveillance in a tertiary care referral centre in South India as a first genomic surveillance study, to our knowledge, of blood culture-confirmed enteric fever in the region.

Methods: Blood culture surveillance was conducted at St John's Medical College Hospital, Bengaluru, between July 2016 and June 2017. The bacterial isolates collected were linked to demographic variables of patients and subjected to WGS. The resulting pathogen genomic data were also globally contextualized to gauge possible phylogeographical patterns.

Results: Hospital-based genomic surveillance for enteric fever in Bengaluru, India, identified 101 Salmonella enterica Typhi and 14 S. Paratyphi A in a 1 year period. Ninety-six percent of isolates displayed non-susceptibility to fluoroquinolones. WGS showed the dominant pathogen was S. Typhi genotype 4.3.1.2 (H58 lineage II). A fluoroquinolone-resistant triple-mutant clone of S. Typhi 4.3.1.2 previously associated with gatifloxacin treatment failure in Nepal was implicated in 18% of enteric fever cases, indicating ongoing inter-regional circulation.

Conclusions: Enteric fever in South India continues to be a major public health issue and is strongly associated with antimicrobial resistance. Robust microbiological surveillance is necessary to direct appropriate treatment and preventive strategies. Of particular concern is the emergence and expansion of the highly fluoroquinolone-resistant triple-mutant S. Typhi clone and its ongoing inter- and intra-country transmission in South Asia, which highlights the need for regional coordination of intervention strategies, including vaccination and longer-term strategies such as improvements to support hygiene and sanitation.
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http://dx.doi.org/10.1093/jac/dkz435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223262PMC
February 2020

A systematic review of antimicrobial resistance of typhoidal in India.

Indian J Med Res 2019 02;149(2):151-163

Department of Paediatrics, University of Oxford & NIHR Oxford Biomedical Research Centre, Oxford, UK.

Background & Objectives: The temporal trends in the development of antimicrobial resistance (AMR) among Salmonella Typhi and Salmonella Paratyphi in India have not been systematically reported. We aimed to systematically review the temporal AMR trends (phenotypic and molecular mechanisms) in bacterial isolates from patients with enteric fever over two decades in India.

Methods: To identify trends in AMR in India, resistance patterns among 4611 individual S. Typhi isolates and 800 S. Paratyphi A isolates, reported from 1992 to 2017 in 40 publications, were analysed. Molecular resistance determinants were extracted from 22 publications and also reviewed in accordance with the PRISMA guidelines. Articles were sourced using a predefined search strategy from different databases.

Results: The analyses suggested that multidrug-resistant (MDR) enteric fever was declining in India and being replaced by fluoroquinolone (FQ) resistance. Mutations in gyrA and parC were key mechanisms responsible for FQ resistance, whereas MDR was largely driven by resistance determinants encoded on mobile genetic elements (plasmids, transposons).

Interpretation & Conclusions: The results reflect the effect of antimicrobial pressure which has been driving AMR in typhoidal Salmonella in India. Understanding these trends is important in planning future approaches to therapy, which serve as a baseline for assessment of the impact of new typhoid conjugate vaccines against these resistant organisms.
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http://dx.doi.org/10.4103/ijmr.IJMR_830_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563740PMC
February 2019

Emergence of new genotypes and lineages of dengue viruses during the 2012-15 epidemics in southern India.

Int J Infect Dis 2019 Jul 11;84S:S34-S43. Epub 2019 Jan 11.

International Vaccine Access Center, Johns Hopkins Bloomberg School of Public Health, 415 N Washington St, Baltimore 21231, USA. Electronic address:

Objectives: To genotypically characterize dengue virus (DENV) isolates among dengue-infected children from 2012-13/2014-15 outbreaks in southern India.

Methods: Children hospitalized with suspected dengue were tested for dengue RT-PCR targeting Capsid-preMembrane (C-prM) and Envelope (Env) regions. Following virologic confirmation (n=612), a representative selection of DENV isolates (n=99) were sequenced for C-prM, aligned using ClustalW and subjected to phylogenetic analysis by maximum-likelihood method in MEGA6.

Results: In 2012-13 (n=113), DENV-3 (44, 38.9%) and DENV-2 (43, 38.1%) predominated; DENV-1 (22, 19.5%) and DENV-4 (1, 0.9%) were less common. The pattern changed in 2014-15 (n=499), when DENV-1 (329, 65.7%) predominated, followed by DENV-2 (97, 21.2%), DENV-3 (36, 6.7%) and DENV-4 (10, 2.0%). Multiple-serotype co-infections occurred in 2.7% and 5.4% in 2012-13 and 2014-15, respectively. Genotype III (GIII) of DENV-1 predominated (85.7%) in 2012-13, ceding to GI predominance (80.8%) in 2014-15. Among DENV-2, 71.9% (23/32) showed distinct clustering suggesting a new lineage, 'GIVc'. All tested DENV-4 were GIC, whose clustering pattern showed the emergence of two distinct clades.

Conclusions: New genotypic/lineage variations in DENV-1 and DENV-2 may have influenced the magnitude and severity of dengue epidemics in southern India during this period. These findings emphasize the role of active surveillance of DENV serotypes/genotypes in aiding outbreak control and vaccine studies.
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http://dx.doi.org/10.1016/j.ijid.2019.01.014DOI Listing
July 2019

A systematic review of antimicrobial resistance in Salmonella enterica serovar Typhi, the etiological agent of typhoid.

PLoS Negl Trop Dis 2018 10 11;12(10):e0006779. Epub 2018 Oct 11.

Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom.

Background: The temporal and spatial change in trends of antimicrobial resistance (AMR) in typhoid have not been systematically studied, and such information will be critical for defining intervention, as well as planning sustainable prevention strategies.

Methodology And Findings: To identify the phenotypic trends in AMR, 13,833 individual S. Typhi isolates, reported from 1973 to 2018 in 62 publications, were analysed to determine the AMR preponderance over time. Separate analyses of molecular resistance determinants present in over 4,000 isolates reported in 61 publications were also conducted. Multi-drug resistant (MDR) typhoid is in decline in Asia in a setting of high fluoroquinolone resistance while it is on the increase in Africa. Mutations in QRDRs in gyrA (S83F, D87N) and parC (S80I) are the most common mechanisms responsible for fluoroquinolone resistance. Cephalosporin resistant S. Typhi, dubbed extensively drug-resistant (XDR) is a real threat and underscores the urgency in deploying the Vi-conjugate vaccines.

Conclusion: From these observations, it appears that AMR in S. Typhi will continue to emerge leading to treatment failure, changes in antimicrobial policy and further resistance developing in S. Typhi isolates and other Gram-negative bacteria in endemic regions. The deployment of typhoid conjugate vaccines to control the disease in endemic regions may be the best defence.
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http://dx.doi.org/10.1371/journal.pntd.0006779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198998PMC
October 2018

Rapid travel to a Zika vaccine: are we heading towards success or more questions?

Expert Opin Biol Ther 2018 11 4;18(11):1171-1179. Epub 2018 Oct 4.

a Oxford Vaccine Group, Department of Paediatrics , University of Oxford and the NIHR Oxford Biomedical Research Centre, The Center for Clinical Vaccinology and Tropical Medicine , Oxford , UK.

Introduction: The emergence of the Zika virus (ZIKV) in Latin America in 2015-2016 led to an expeditious search for vaccine candidates, with a DNA-based candidate having progressed to Phase II. However, several features of ZIKV infection and epidemiology are not understood, which may be key to maximizing efficacy and ensuring safety of ZIKV vaccines.

Areas Covered: Conceivable problems related to vaccine development and policy include: (1) paucity of diagnostics to satisfactorily discriminate between past ZIKV and dengue virus (DENV) exposure; (2) insufficient knowledge of the mechanisms of ZIKV neurovirulence, amongst other unknowns in the biology of this infection, is particularly relevant from a vaccine safety perspective; and (3) the potential for disease enhancement, as observed with DENV infection and vaccine.

Expert Opinion: Vaccine candidates that entered phase I/II trials have demonstrated protection in naïve animal models, while ZIKV epidemics occurred in populations that had encountered DENV before. The resulting cross-reactive antibodies pose problems for reliable serologic diagnostic assays, and for the potential of disease enhancement. The alleged neurological complications also warrant further exploration in order to reassure regulators of the safety profile of these vaccines in target populations. These research aspects should be an integral part of the efforts to develop a vaccine.
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http://dx.doi.org/10.1080/14712598.2018.1526277DOI Listing
November 2018

Typhoid and paratyphoid fever: a call to action.

Curr Opin Infect Dis 2018 10;31(5):440-448

Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and NIHR Oxford Biomedical Research Centre, Oxford, UK.

Purpose Of Review: Enteric fever remains a major global-health concern, estimated to be responsible for between 11.9 and 26.9 million cases annually. Long-term prevention of enteric fever will require improved access to safe drinking water combined with investment in sanitation and hygiene interventions. In the short-to-medium term, new control strategies for typhoid fever have arrived in the form of typhoid Vi-conjugate vaccines (TCVs), offering hope that disease control can be achieved in the near future.

Recent Findings: The diagnosis of enteric fever is complicated by its nonspecific clinical presentation, coupled with the low sensitivity of commonly used diagnostics. Investment in diagnostics has the potential to improve management, to refine estimates of disease burden and to facilitate vaccine impact studies. A new generation of reliable, diagnostic tests is needed that are simultaneously accessible, cost-effective, sensitive, and specific. The emergence and global dissemination of multidrug-resistant, fluoroquinolone-resistant, and extensively drug-resistant (XDR) strains of Salmonella Typhi emphasizes the importance of continued surveillance and appropriate antibiotic stewardship, integrated into a global strategy to address antimicrobial resistance (AMR). Current empirical treatment guidelines are out of date and should be updated to respond to local trends in AMR, so as to guide treatment choices in the absence of robust diagnostics and laboratory facilities. In September 2017, the WHO Strategic Advisory Group of Experts (SAGE) immunization recommended the programmatic use of TCVs in high burden countries. Ongoing and future studies should aim to study the impact of these vaccines in a diverse range of setting and to support the deployment of TCVs in high-burden countries.

Summary: The advent of new generation TCVs offers us a practical and affordable public-health tool that - for the first time - can be integrated into routine childhood immunization programmes. In this review, we advocate for the deployment of TCVs in line with WHO recommendations, to improve child health and limit the spread of antibiotic-resistant S. Typhi.
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http://dx.doi.org/10.1097/QCO.0000000000000479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319573PMC
October 2018

Resilience in Wives of persons with Alcoholism: An Indian exploration.

Indian J Psychiatry 2018 Jan-Mar;60(1):84-89

Department of Psychiatry, St. John's Medical College Hospital, Bengaluru, Karnataka, India.

Context: Mental health has currently shifted focus from "deficit" to strength-based approaches such as Resilience. Coping styles and personality factors have been well studied in Wives of persons with Alcoholism (WopA) but not Resilience. Alcohol dependence in spouse is seen as an adversity.

Aims: To evaluate Resilience in the WopA and explore its relationship with marital quality and clinical variables of Alcohol Dependence in their husbands.

Settings And Design: A cross-sectional study in a tertiary care hospital in Bangalore, Karnataka.

Subjects And Methods: WopA (n=34) between 25-55 years, were assessed for Resilience using Resilience Scale for Adults (RSA), while marital quality was assessed using Marital Quality Scale (MQS). The Severity of Alcohol Dependence, Age of onset of Initiation, Age of onset of Problem Drinking, and Age of onset of Dependence were evaluated in their husbands.

Statistical Analysis: Independent sample -test, Chi-square test, and Pearson's correlation were used.

Results: Majority of the WopA (82%) scored low on the RSA. Low Resilience (LR) WopA scored significantly lower on all factors of RSA except the perception of future; in comparison to High Resilience (HR) WopA. Additionally, the LR WopA reported significantly poorer marital quality.

Conclusions: Most WopA had low Resilience. LR WopA also had significantly poor marital quality. These findings need to be studied further in a larger population with culturally appropriate scales. The low scoring Resilience factors amongst WopA may be utilized in strength-based psychotherapeutic approaches. There is a need to improve the understanding of Resilience and its assessment in this population.
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http://dx.doi.org/10.4103/psychiatry.IndianJPsychiatry_271_14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5914269PMC
May 2018

Laboratory and molecular surveillance of paediatric typhoidal Salmonella in Nepal: Antimicrobial resistance and implications for vaccine policy.

PLoS Negl Trop Dis 2018 04 23;12(4):e0006408. Epub 2018 Apr 23.

Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom.

Background: Children are substantially affected by enteric fever in most settings with a high burden of the disease, including Nepal. However pathogen population structure and transmission dynamics are poorly delineated in young children, the proposed target group for immunization programs. Here we present whole genome sequencing and antimicrobial susceptibility data on 198 S. Typhi and 66 S. Paratyphi A isolated from children aged 2 months to 15 years of age during blood culture surveillance at Patan Hospital, Nepal, 2008-2016.

Principal Findings: S. Typhi was the dominant agent and comprised several distinct genotypes, dominated by 4.3.1 (H58). The heterogeneity of genotypes in children under five was reduced compared to data from 2005-2006, attributable to ongoing clonal expansion of H58. Most isolates (86%) were non-susceptible to fluoroquinolones, associated mainly with S. Typhi H58 lineage II and S. Paratyphi A harbouring mutations in the quinolone resistance-determining region (QRDR); non-susceptible strains from these groups accounted for 50% and 25% of all isolates. Multi-drug resistance (MDR) was rare (3.5% of S. Typhi, 0 S. Paratyphi A) and restricted to chromosomal insertions of resistance genes in H58 lineage I strains. Temporal analyses revealed a shift in dominance from H58 Lineage I to H58 Lineage II, with the latter being significantly more common after 2010. Comparison to global data sets showed the local S. Typhi and S. Paratyphi A strains had close genetic relatives in other South Asian countries, indicating regional strain circulation. Multiple imports from India of ciprofloxacin-resistant H58 lineage II strains were identified, but these were rare and showed no evidence of clonal replacement of local S. Typhi.

Significance: These data indicate that enteric fever in Nepal continues to be a major public health issue with ongoing inter- and intra-country transmission, and highlights the need for regional coordination of intervention strategies. The absence of a S. Paratyphi A vaccine is cause for concern, given its prevalence as a fluoroquinolone resistant enteric fever agent in this setting.
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http://dx.doi.org/10.1371/journal.pntd.0006408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933809PMC
April 2018

Barriers and enablers to skin-to-skin contact at birth in healthy neonates - a qualitative study.

BMC Pediatr 2018 02 9;18(1):48. Epub 2018 Feb 9.

Department of Neonatology, St. John's Medical College Hospital, Sarjapur Road, Koramangala, Bangalore, 560034, India.

Background: Skin to skin contact (SSC) at birth is the standard of care for newborns without risk factors. However, implementation of SSC at birth has been far from optimal. A qualitative study was undertaken to determine the barriers, enablers and potential solutions to implementation of SSC at birth in healthy newborn infants in a level III neonatal-care facility in Bangalore, India.

Methods: Consultants and residents/postgraduates (PG) from the departments of Obstetrics (n = 19) and Pediatrics (n = 14) and nurses (n = 8) in the labor room (LR) participated in the study. In depth interviews (IDI) and focus group discussions (FGD) were carried out with an interview guide and a moderators' guide containing inbuilt probes. Subjects of FGD were homogenous. All IDI and FGD were audio-taped, transcribed and analyzed using N VIVO version 9 (using free and tree nodes). Two authors separately coded the transcripts. Major and minor themes were identified. Rigor was ensured by triangulation and theoretical saturation. Informed consent and ethical approval was obtained.

Results: All subjects were aware of SSC at birth, some of its benefits and had practiced SSC. The major barriers identified were lack of personnel (nurses), time constraint, difficulty in deciding on eligibility for SSC, safety concerns, interference with clinical routines, and interdepartmental issues. Recall of an adverse event during SSC was also a major barrier. Furthermore, we found that most participants considered 1 h as impractical; and promoted 5-15 min SSC. Minor themes were gender bias of the newborn and cultural practices. The participants offered solutions such as assigning a helper exclusively for SSC, allowing a family member into the LR, continuing SSC after initial routines, antenatal counselling, constant reminders in the form of periodic sessions with audiovisual aids or posters in the obstetrics ward, training of new nurses and PG, and inclusion of SSC in medical and nursing curriculum.

Conclusions: The major barriers to SSC at birth are lack of personnel, time constraint and safety concerns. Training, designated health personnel for SSC and teamwork are the key interventions likely to improve SSC at birth.
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http://dx.doi.org/10.1186/s12887-018-1033-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5807736PMC
February 2018

Monitoring the Postnatal Growth of Preterm Infants: A Paradigm Change.

Pediatrics 2018 02 4;141(2). Epub 2018 Jan 4.

Nuffield Department of Obstetrics & Gynaecology and Oxford Maternal & Perinatal Health Institute, Green Templeton College and.

There is no consensus regarding how the growth of preterm infants should be monitored or what constitutes their ideal pattern of growth, especially after term-corrected age. The concept that the growth of preterm infants should match that of healthy fetuses is not substantiated by data and, in practice, is seldom attained, particularly for very preterm infants. Hence, by hospital discharge, many preterm infants are classified as postnatal growth-restricted. In a recent systematic review, 61 longitudinal reference charts were identified, most with considerable limitations in the quality of gestational age estimation, anthropometric measures, feeding regimens, and how morbidities were described. We suggest that the correct comparator for assessing the growth of preterm infants, especially those who are moderately or late preterm, is a cohort of preterm newborns (not fetuses or term infants) with an uncomplicated intrauterine life and low neonatal and infant morbidity. Such growth monitoring should be comprehensive, as recommended for term infants, and should include assessments of postnatal length, head circumference, weight/length ratio, and, if possible, fat and fat-free mass. Preterm postnatal growth standards meeting these criteria are now available and may be used to assess preterm infants until 64 weeks' postmenstrual age (6 months' corrected age), the time at which they overlap, without the need for any adjustment, with the World Health Organization Child Growth Standards for term newborns. Despite remaining nutritional gaps, 90% of preterm newborns (ie, moderate to late preterm infants) can be monitored by using the International Fetal and Newborn Growth Consortium for the 21st Century Preterm Postnatal Growth Standards from birth until life at home.
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http://dx.doi.org/10.1542/peds.2017-2467DOI Listing
February 2018

An Appraisal of the Clinical Features of Pediatric Enteric Fever: Systematic Review and Meta-analysis of the Age-Stratified Disease Occurrence.

Clin Infect Dis 2017 Jun;64(11):1604-1611

Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the National Institute for Health Research Oxford Biomedical Research Centre and.

Children bear a substantial proportion of the enteric fever disease burden in endemic areas. Controversy persists regarding which age groups are most affected, leading to uncertainty about optimal intervention strategies. We performed a systematic review and meta-analysis of studies in Asia and Africa to compare the relative proportion of children with enteric fever in the age groups <5 years, 5-9 years, and 10-14 years. Overall, studies conducted in Africa showed a relatively smaller occurrence of disease in the youngest age group, whereas in Asia the picture was more mixed with a very large degree of heterogeneity in estimates. The clinical features of enteric fever reviewed here differ between younger and older children and adults, likely leading to further uncertainty over disease burden. It is evident from our review that preschool children and infants also contribute a significant proportion of disease burden but have not been adequately targeted via vaccination programs, which have been focusing primarily on school-based vaccination campaigns.
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http://dx.doi.org/10.1093/cid/cix229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5434381PMC
June 2017

Assessment of Neonatal Pain During Heel Prick: Lancet vs Needle-A Randomized Controlled Study.

J Trop Pediatr 2017 10;63(5):346-351

Department of Neonatology, St. John's Medical College Hospital, Bengaluru 560034, India.

Background: Heel prick is a frequent painful procedure in newborns. A lancet or a 26-gauge needle is used for a heel prick in India.

Objective: To compare the pain caused by heel prick with a lancet or a 26-gauge needle in newborns admitted in the neonatal intensive care unit (NICU) using the preterm infant pain profile (PIPP).

Methods: This randomized controlled trial was conducted over 2 months in a Level III NICU with a sample size of 40 subjects (20 in each group), which was required for the study to have a power of 80% with an alpha error of 0.05. Hemodynamically stable newborns on at least those on partial oral feeds undergoing heel prick for routine glucose monitoring were randomized into two groups within 48 h of NICU admission after informed parental consent: heel prick with a lancet or with a 26-gauge needle using computer-generated random numbers. Two milliliters of expressed breast milk was given 2 min before the heel prick. Pain before, during and after (1 and 5 min) was assessed using the PIPP score. The primary outcome measure was the PIPP score. The secondary outcome measures were the duration of audible cry and the number of pricks needed for an adequate sample. Statistical analysis was done using the Mann Whitney U test and Friedman's test on SPSS v.21. A p value of < 0.05 was significant.

Results: There were 40 neonates, 24 males and 16 females included in the study with a median age of 7 days. The mean birth weight was 2441 g (SD: 699) at a mean gestation of 34.4 weeks (SD: 3.2). The median PIPP scores at 0-30 s after heel prick were 7.05 ± 3.57 with a lancet vs. 9.35 ± 3.68 a needle (p = 0.052). There was a significantly lower duration of audible cry with use of lancet (10.5 ± 18.5 s vs. 75.2 ± 12.0 s with needle; p = 0.03). All heel pricks resulted in adequate sampling.

Conclusion: Heel prick with a lancet causes less crying than a 26-gauge needle, though the PIPP scores are not significantly different.
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http://dx.doi.org/10.1093/tropej/fmw093DOI Listing
October 2017

Five-year analysis of rickettsial fevers in children in South India: Clinical manifestations and complications.

J Infect Dev Ctries 2016 Jun 30;10(6):657-61. Epub 2016 Jun 30.

St Johns' Medical College Hospital, Bangalore, India.

Introduction: Rickettsial infections are re-emerging in the Indian subcontinent, especially among children. Understanding geographical and clinical epidemiology will facilitate early diagnosis and management.

Methodology: Children aged <18yrs hospitalized with clinically-diagnosed rickettsial fever were reviewed retrospectively. Frequency distributions and odds ratios were calculated from tabulated data.

Results: Among 262 children hospitalized between January 2008-December 2012, median age was five years, and 61% were male children. Hospitalized cases increased steadily every year, with the highest burden (74%) occurring between September and January each year. Mean duration of fever was 11.5 days. Rash was present in 54.2% (142/262) of children, with 37.0% involving palms and soles. Prevalence of malnutrition was high (45% of children were underweight and 28% had stunting). Retinal vasculitis was seen in 13.7% (36/262), and the risk appeared higher in females. Severe complications were seen in 29% (purpura fulminans, 7.6%; meningitis and meningoencephalitis, 28%; septic shock, 1.9%; acute respiratory distress syndrome, 1.1%). Complications were more likely to occur in anemic children. Positive Weil-Felix test results (titers ≥1:160) were seen in 70% of cases. Elevated OX-K titers suggestive of scrub typhus were seen in 80% (147/184). Patients were treated with chloramphenicol (32%) or doxycycline (68%). Overall mortality among hospitalised children was 1.9%.

Conclusions: This five-year analysis from southern India shows a high burden and increasing trend of rickettsial infections among children. The occurrence of retinal vasculitis and a high rate of severe complications draw attention to the need for early diagnosis and management of these infections.
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http://dx.doi.org/10.3855/jidc.6822DOI Listing
June 2016

Prevalence and Correlates of HIV Disclosure Among Children and Adolescents in Low- and Middle-Income Countries: A Systematic Review.

J Dev Behav Pediatr 2016 Jul-Aug;37(6):496-505

*Department of Pediatrics, St. John's Medical College Hospital, Bangalore, India; †Department of Public Health Sciences, Global Health, Karolinska Institutet, Stockholm, Sweden.

Objective: Disclosure of HIV status among children and adolescents living with HIV has both beneficial and challenging aspects. To address existing knowledge gaps and update the literature on childhood disclosure, we conducted a systematic review on caregivers' perceptions and practices of HIV disclosure in low- and middle-income countries (LMICs).

Methods: Standard databases were searched for studies conducted in LMICs, published in English between 2004 and 2015. Excluded articles were reviews or case reports, and those not reporting childhood disclosure. Data regarding prevalence, correlates and impact of disclosure, were presented as frequencies.

Results: Two authors independently screened 982 articles. After applying eligibility criteria, 22 articles representing 12 countries and 2,843 children were reviewed. The proportion of fully disclosed children ranged from 1.7% to 41.0%. Up to 49.5% children were provided "deflected" information (use of a non-HIV-related reason for explaining illness and health care visits). Factors associated with full disclosure included antiretroviral treatment initiation and caregivers' felt need for maintaining optimal adherence. Barriers to disclosure included fear of negative psychological reactions and inadvertent disclosure to others. Caregivers perceived a strong need for active participation from health care providers to aid the process of disclosure.

Conclusions: Full disclosure of HIV status was not common among children and adolescents in LMICs, while the practice of deflected disclosure was prominent. Caregivers perceived the need for support from health care providers during the disclosure process. Evidence-based guidelines incorporating the developmental status of the child, locally prevalent cultures, and caregiver perceptions are prerequisite to enhancing disclosure in these settings.
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http://dx.doi.org/10.1097/DBP.0000000000000303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949066PMC
December 2017

PAIN--perception and assessment of painful procedures in the NICU.

J Trop Pediatr 2014 Dec 21;60(6):422-7. Epub 2014 Jul 21.

Department of Neonatology, St. John's Medical College, Bangalore, Karnataka 560034, India.

This prospective cross-sectional study was undertaken to determine the frequency of procedural pain among 101 neonates in the first 14 days of admission to a neonatal intensive care unit (NICU) in South India and to study the perception of health-care professionals (HCP) about newborn procedural pain. The total number of painful procedures was 8.09 ± 5.53 per baby per day and 68.32 ± 64.78 per baby during hospital stay. The most common procedure was heel prick (30%). The HCP were administered a questionnaire to assess their perception of pain for various procedures. Procedures were perceived as more painful by nurses than by doctors. Chest tube placements and lumbar puncture were considered most painful. This study shows that the neonates in the NICU in developing countries experience many painful procedures. The awareness about this intensity of pain should provide a valuable tool in formulating pain-reduction protocols for management in low resource settings.
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http://dx.doi.org/10.1093/tropej/fmu039DOI Listing
December 2014