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Article ; Online: The next frontier in vaccine design: blending immune correlates of protection into rational vaccine design.

Britto, Carl / Alter, Galit

2022 Volume 78, Page(s) 102234

Abstract: Despite the extraordinary speed and success in SARS-Cov-2 vaccine development, the emergence of variants of concern perplexed the vaccine development community. Neutralizing antibodies waned antibodies waned and were evaded by viral variants, despite the ...

Abstract	Despite the extraordinary speed and success in SARS-Cov-2 vaccine development, the emergence of variants of concern perplexed the vaccine development community. Neutralizing antibodies waned antibodies waned and were evaded by viral variants, despite the preservation of protection against severe disease and death across vaccinated populations. Similar to other vaccine design efforts, the lack of mechanistic correlates of immunity against Coronavirus Disease 2019, raised questions related to the need for vaccine redesign and boosting. Hence, our limited understanding of mechanistic correlates of immunity - across pathogens - remains a major obstacle in vaccine development. The identification and incorporation of mechanistic correlates of immunity are key to the accelerated design of highly impactful globally relevant vaccines. Systems-biology tools can be applied strategically to define a complete understanding of mechanistic correlates of immunity. Embedding immunological dissection and target immune profile identification, beyond canonical antibody binding and neutralization, may accelerate the design and success of durable protective vaccines.
MeSH term(s)	Humans ; Viral Vaccines ; COVID-19 Vaccines ; COVID-19/prevention & control ; SARS-CoV-2 ; Antibodies, Neutralizing ; Antibodies, Viral
Chemical Substances	Viral Vaccines ; COVID-19 Vaccines ; Antibodies, Neutralizing ; Antibodies, Viral
Language	English
Publishing date	2022-08-13
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1035767-1
ISSN	1879-0372 ; 0952-7915
ISSN (online)	1879-0372
ISSN	0952-7915
DOI	10.1016/j.coi.2022.102234
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Article ; Online: Tele-ICU enabled management of an organ donor in an under-resourced setting.

Dasari, Prudhvi / Reddy, Maheeja / Parmar, Dileep Singh / Britto, Carl

BMJ case reports

2024 Volume 17, Issue 4

Abstract: A man in his 30s was involved in a road traffic crash in a small town in India, not equipped to deal with cases of brainstem death. He was declared brain-dead after a few hours. The patient's information was forwarded to organ specialists across the ... ...

Abstract	A man in his 30s was involved in a road traffic crash in a small town in India, not equipped to deal with cases of brainstem death. He was declared brain-dead after a few hours. The patient's information was forwarded to organ specialists across the country, with the goal of preserving the patient's organs for donation via a tele-ICU model. The team comprising bedside doctors and remote intensivists communicating via an indigenously developed tele-ICU platform managed the patient for 24 hours, following treatment protocols and providing critical care to ensure that the patient's vital organs were optimally perfused. The following morning, specialist teams from a nearby city arrived at the local hospital to retrieve the patient's organs. This fast-tracked organ retrieval and transplant process were made possible through advances in technology and the involvement of specialists from other parts of the country through this tele-ICU model.
MeSH term(s)	Humans ; Male ; Brain Death ; Critical Care/methods ; Intensive Care Units ; Telemedicine ; Tissue Donors ; Adult
Language	English
Publishing date	2024-04-16
Publishing country	England
Document type	Case Reports ; Journal Article
ISSN	1757-790X
ISSN (online)	1757-790X
DOI	10.1136/bcr-2023-255348
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Article ; Online: A Proof-of-Concept Model for Implementing a "Smart-NICU" to Improve Infant Mortality.

Hilker, Sidney / Mancho, Amundam / Srivatsava, Geetanjali / Raman, Dileep / Mathias, Sitarah / Brewster, Ryan / Britto, Carl

Journal of intensive care medicine

2024 , Page(s) 8850666241247532

Abstract: Low- and middle-income countries face limited critical care capacity due to constraints in staffing, resources, and technology. "Smart ICUs" that integrate telehealth to augment care delivery, communication, and data integration have the potential to ... ...

Abstract	Low- and middle-income countries face limited critical care capacity due to constraints in staffing, resources, and technology. "Smart ICUs" that integrate telehealth to augment care delivery, communication, and data integration have the potential to bridge these gaps and reduce preventable morbidity and mortality. While their efficacy has been well validated in adult populations, applications of Smart-ICU services in the neonatal population have not been studied. Neonatal intensive care units (NICUs) in India using a common Smart-NICU platform, developed by CloudPhysician, utilize a hub-and-spokes framework along with locally designed technology to facilitate remote patient care in collaboration with local health systems. In this article, we investigate the operational characteristics and performance outcomes for Smart-NICU deployment from the 18 NICUs and 214 beds deployed to date. These findings highlight the potential impact of Smart-NICUs and establish generalizable principles for implementation in low-resource settings.
Language	English
Publishing date	2024-04-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	632828-3
ISSN	1525-1489 ; 0885-0666
ISSN (online)	1525-1489
ISSN	0885-0666
DOI	10.1177/08850666241247532
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Article ; Online: A pragmatic calibration of the ROX index to predict outcome of nasal high-flow therapy in India.

Brewster, Ryan / Mathias, Sitarah / Sarvode, Suraj / Unnikrishnan, Dileep / Raman, Dileep / Foy, Brody / Britto, Carl

Journal of critical care

2024 Volume 82, Page(s) 154812

Abstract: Purpose: Identifying thresholds at which the ROX index would satisfactorily predict HFNC failure across heterogenous resourced contexts is necessary for clinical use.: Methods: Patients ≥18 years admitted to 30 diverse ICUs across 10 states in India ... ...

Abstract	Purpose: Identifying thresholds at which the ROX index would satisfactorily predict HFNC failure across heterogenous resourced contexts is necessary for clinical use. Methods: Patients ≥18 years admitted to 30 diverse ICUs across 10 states in India who required HFNC for respiratory support were retrospectively included in this study. Patient data and hourly ROX indices were then analyzed and contextualized to clinical outcomes as well as with ROX index thresholds in other regions of the world. Measurements and main results: Among the 614 patients included, 276 (44.9%) required respiratory escalation. Pneumonia was the most common diagnosis on admission. Receiver operating characteristic curve analysis revealed that a baseline ROX score of 7.86 was similar to 4.88 in other populations which was confirmed by Kaplan-Mier curves (hazard ratio,3.58 (2.72-4.69, p < 0.001)). ROX scores at 11.84 or 5.89 had roles in screening and confirming HFNC failure. The index performed poorly in a subset of patients who died without respiratory escalation. The ROX index was most predictive in the initial hours of ICU admission and a longer duration of HFNC was associated with more severe outcomes. Conclusions: When optimally calibrated this index can using a method that can reliably predict the risk of HFNC failure among ICU patients from diverse settings.
Language	English
Publishing date	2024-04-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	632818-0
ISSN	1557-8615 ; 0883-9441
ISSN (online)	1557-8615
ISSN	0883-9441
DOI	10.1016/j.jcrc.2024.154812
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Article ; Online: A rare presentation of antisynthetase syndrome requiring intensive care in the midst of a COVID wave.

Arya, Akhila / Anand, Sanu / Kumar, Sandesh / Britto, Carl

Modern rheumatology case reports

2022 Volume 7, Issue 2, Page(s) 394–398

Abstract: A 24-year-old female with pneumonia two months prior presented with fever, cough, and worsening dyspnoea in the midst of a COVID-19 spike. Her initial episode was treated as COVID-19 pneumonia. On presentation, her chest computed tomography was ... ...

Abstract	A 24-year-old female with pneumonia two months prior presented with fever, cough, and worsening dyspnoea in the midst of a COVID-19 spike. Her initial episode was treated as COVID-19 pneumonia. On presentation, her chest computed tomography was suggestive of bilateral lower zone organising pneumonia with mild fibrosis and was attributed to post-COVID sequelae with an infective exacerbation. Oral steroids and antibiotics were administered, following which she had initial improvement and then subsequent deterioration requiring intensive care unit (ICU) care. A detailed clinical examination (in-person and virtually) at this point revealed the presence of pigmented rashes over the knuckles and weakness of hip muscles. Laboratory work showed elevated creatine kinase levels and positive anti-Ro and anti-Jo1 antibodies, which pointed to a diagnosis of antisynthetase syndrome. Unique attributes of this case include younger age of presentation in an atypical ethnic group, which are possibly incited by COVID-19 infection in the peak of a COVID-19 wave. The work-up, diagnosis, and initial management of this patient were carried out through a hybrid ICU model, which functioned as a traditional ICU in the day and a tele-ICU at night with an appropriate network of subspecialists including rheumatologists consulting, thus highlighting a collaborative model in a low-resource setting capable of managing rare cases even in the midst of increasing critical care needs during the pandemic.
MeSH term(s)	Female ; Humans ; Young Adult ; Adult ; COVID-19/complications ; COVID-19/diagnosis ; Myositis/complications ; Myositis/diagnosis ; Critical Care ; Anti-Bacterial Agents/therapeutic use
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2022-11-21
Publishing country	England
Document type	Case Reports ; Journal Article
ISSN	2472-5625
ISSN (online)	2472-5625
DOI	10.1093/mrcr/rxac088
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Article ; Online: The effect of exchange transfusion on mortality in neonatal sepsis: a meta-analysis.

Mathias, Sitarah / Balachander, Bharathi / Bosco, Ashish / Britto, Carl / Rao, Suman

European journal of pediatrics

2021 Volume 181, Issue 1, Page(s) 369–381

Abstract: Although antimicrobials are the cornerstone of neonatal sepsis management, adjunctive therapies are required to improve outcomes. The aim of our study was to evaluate the effect of exchange transfusion (ET) on mortality (primary outcome) in neonatal ... ...

Abstract	Although antimicrobials are the cornerstone of neonatal sepsis management, adjunctive therapies are required to improve outcomes. The aim of our study was to evaluate the effect of exchange transfusion (ET) on mortality (primary outcome) in neonatal sepsis, as well as on immunoglobulin, complement and neutrophil levels and assess its complications (secondary outcomes). Databases searched include PubMed, NCBI, Google Scholar, CINHAL, Ovid and Scopus. Randomized controlled trials (RCTs), controlled observational studies (COSs) and uncontrolled observational studies (UOSs) reporting mortality data from using ET in neonatal sepsis were included. Studies with additional interventions, non-septic ET indications and populations aged > 28 days were excluded. Data extracted include demographics, features of study, sepsis and ET, as well as mortality rates, immunological and laboratory changes and complications. Data was meta-analysed and displayed using forest plots. The meta-analysis of 14 studies (3 RCTs, 11 COSs) revealed a mortality benefit in septic neonates who underwent ET-RR 0.72 (CI 0.61-0.86, p = 0.01) and a significant increase in pooled immunological parameters (immunoglobulin, complement levels) (SMD 1.13, [0.25, 2.02], p = 0.02) and neutrophil levels (SMD 1.07 [0.04, 2.11], p = 0.03) compared to controls. The descriptive analysis of 9 UOSs revealed thrombocytopenia as the most frequently reported complication (n = 48). Moderate-high risk of bias was largely due to inadequate sample sizes and follow-up durations.Conclusion: Currently, the use of ET in neonatal sepsis is not directly recommended due to low certainty of evidence, inadequate power and moderate-high risk of bias and heterogeneity.Trial registration: PROSPERO (CRD42020176629) ( https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=176629 ) What is Known: • Exchange transfusion is one of the adjunctive methods for treatment of neonatal sepsis. What is New: • The pooled analysis of all studies shows that exchange transfusion has a low certainty of evidence in the context of neonatal mortality. However, at this point, this intervention cannot be refuted or recommended due to heterogeneity of studies and inadequate power.
MeSH term(s)	Humans ; Infant Mortality ; Infant, Newborn ; Neonatal Sepsis/therapy ; Sepsis/therapy
Language	English
Publishing date	2021-08-05
Publishing country	Germany
Document type	Journal Article ; Meta-Analysis
ZDB-ID	194196-3
ISSN	1432-1076 ; 0340-6199 ; 0943-9676
ISSN (online)	1432-1076
ISSN	0340-6199 ; 0943-9676
DOI	10.1007/s00431-021-04194-w
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Article ; Online: Correction to: Interventions to promote cost-effectiveness in adult intensive care units: consensus statement and considerations for best practice from a multidisciplinary and multinational eDelphi study.

Kansal, Amit / Latour, Jos M / See, Kay Choong / Rai, Sumeet / Cecconi, Maurizio / Britto, Carl / Conway Morris, Andrew / Dominic Savio, Raymond / Nadkarni, Vinay M / Rao, B K / Mishra, Rajesh

Critical care (London, England)

2024 Volume 28, Issue 1, Page(s) 121

Language	English
Publishing date	2024-04-12
Publishing country	England
Document type	Published Erratum
ZDB-ID	2041406-7
ISSN	1466-609X ; 1364-8535
ISSN (online)	1466-609X
ISSN	1364-8535
DOI	10.1186/s13054-024-04888-1
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Article ; Online: Distributions of candidate vaccine Targets, virulence Factors, and resistance features of invasive group B Streptococcus using Whole-Genome Sequencing: A Multicenter, population-based surveillance study.

Ji, Wenjing / Zhou, Haijian / Li, Jie / Britto, Carl D / Liu, Zheliang / Zhang, Wen / Du, Jiaxi / Madhi, Shabir A / Kwatra, Gaurav / Dangor, Ziyaad / Jin, Zhengjiang / Zhao, Hang / Zhao, Yifei / Fang, Yu / Li, Juan

Vaccine

2024

Abstract: Background: Group B Streptococcus (GBS) is a leading cause of morbidity and mortality in young infants worldwide. This study aimed to investigate candidate GBS vaccine targets, virulence factors, and antimicrobial resistance determinants.: Methods: ... ...

Abstract	Background: Group B Streptococcus (GBS) is a leading cause of morbidity and mortality in young infants worldwide. This study aimed to investigate candidate GBS vaccine targets, virulence factors, and antimicrobial resistance determinants. Methods: We used whole-genome sequencing to characterize invasive GBS isolates from infants < 3 months of age obtained from a multicenter population-based study conducted from 2015 to 2021 in China. Results: Overall, seven serotypes were detected from 278 GBS isolates, four (Ia, Ib, III, V) of which accounted for 97.8 %. We detected 30 sequence types (including 10 novel types) that were grouped into six clonal complexes (CCs: CC1, CC10, CC17, CC19, CC23 and CC651); three novel ST groups in CC17 were detected, and the rate of CC17, considered a hyperinvasive neonatal clone complex, was attached to 40.6 % (113/278). A total of 98.9 % (275/278) of isolates harbored at least one alpha-like protein gene. All GBS isolates contained at least one of three pilus backbone determinants and the pilus types PI-2b and PI-1 + PI-2a accounted for 79.8 % of the isolates. The 112 serotype III/CC17 GBS isolates were all positive for hvgA. Most of the isolates (75.2 %) were positive for serine-rich repeat glycoprotein determinants (srr1or srr2). Almost all isolates possessed cfb (99.6 %), c1IE (100 %), lmb (95.3 %) or pavA (100 %) gene. Seventy-seven percent of isolates harboured more than three antimicrobial resistance genes with 28.4 % (79/278) gyrA quinoloneresistancedeterminants mutation, 83.8 % (233/278) carrying tet cluster genes and 77.3 % (215/278) carrying erm genes which mediated fluoroquinolone, tetracycline and clindamycin resistance, respectively." Conclusions: The findings from this large whole-genome sequence of GBS isolates establish important baseline data required for further surveillance and evaluating the impact of future vaccine candidates.
Language	English
Publishing date	2024-04-30
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2024.04.062
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Zs.A 1930: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Neonatal and infant mortality associated with spina bifida: A systematic review and meta-analysis.

Ho, Peter / Quigley, Maria A / Tatwavedi, Dharamveer / Britto, Carl / Kurinczuk, Jennifer J

PloS one

2021 Volume 16, Issue 5, Page(s) e0250098

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Female ; Humans ; Infant ; Infant Mortality ; Infant, Newborn ; Pregnancy ; Premature Birth ; Spinal Dysraphism/mortality
Language	English
Publishing date	2021-05-12
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Systematic Review
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0250098
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Article ; Online: Typhoid and paratyphoid fever: a call to action.

Gibani, Malick M / Britto, Carl / Pollard, Andrew J

Current opinion in infectious diseases

2018 Volume 31, Issue 5, Page(s) 440–448

Abstract: 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 ...

Abstract	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.
MeSH term(s)	Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Antimicrobial Stewardship ; Communicable Disease Control/methods ; Diagnostic Tests, Routine/methods ; Disease Transmission, Infectious/prevention & control ; Drug Resistance, Bacterial ; Epidemiological Monitoring ; Global Health ; Humans ; Paratyphoid Fever/diagnosis ; Paratyphoid Fever/drug therapy ; Paratyphoid Fever/epidemiology ; Paratyphoid Fever/prevention & control ; Typhoid Fever/diagnosis ; Typhoid Fever/drug therapy ; Typhoid Fever/epidemiology ; Typhoid Fever/prevention & control ; Typhoid-Paratyphoid Vaccines/immunology ; Typhoid-Paratyphoid Vaccines/isolation & purification
Chemical Substances	Anti-Bacterial Agents ; Typhoid-Paratyphoid Vaccines
Language	English
Publishing date	2018-08-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	645085-4
ISSN	1473-6527 ; 1535-3877 ; 0951-7375 ; 1355-834X
ISSN (online)	1473-6527 ; 1535-3877
ISSN	0951-7375 ; 1355-834X
DOI	10.1097/QCO.0000000000000479
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