Imperial College London

DrElizabethWhittaker

Faculty of MedicineDepartment of Infectious Disease

Honorary Clinical Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 2063e.whittaker

 
 
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Location

 

PaediatricsNorfolk PlaceSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
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56 results found

Speirs L, Whittaker E, 2021, Fifteen-minute consultation: What do I do with a baby born to a mother with tuberculosis?, ARCHIVES OF DISEASE IN CHILDHOOD-EDUCATION AND PRACTICE EDITION, Vol: 106, Pages: 210-215, ISSN: 1743-0585

Journal article

McArdle AJ, Vito O, Patel H, Seaby EG, Shah P, Wilson C, Broderick C, Nijman R, Tremoulet AH, Munblit D, Ulloa-Gutierrez R, Carter MJ, De T, Hoggart C, Whittaker E, Herberg JA, Kaforou M, Cunnington AJ, Levin Met al., 2021, Treatment of multisystem inflammatory syndrome in children, New England Journal of Medicine, Vol: 385, Pages: 11-22, ISSN: 0028-4793

BACKGROUNDEvidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2.METHODSWe performed an international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone. There were two primary outcomes: the first was a composite of inotropic support or mechanical ventilation by day 2 or later or death; the second was a reduction in disease severity on an ordinal scale by day 2. Secondary outcomes included treatment escalation and the time until a reduction in organ failure and inflammation.RESULTSData were available regarding the course of treatment for 614 children from 32 countries from June 2020 through February 2021; 490 met the World Health Organization criteria for MIS-C. Of the 614 children with suspected MIS-C, 246 received primary treatment with IVIG alone, 208 with IVIG plus glucocorticoids, and 99 with glucocorticoids alone; 22 children received other treatment combinations, including biologic agents, and 39 received no immunomodulatory therapy. Receipt of inotropic or ventilatory support or death occurred in 56 patients who received IVIG plus glucocorticoids (adjusted odds ratio for the comparison with IVIG alone, 0.77; 95% confidence interval [CI], 0.33 to 1.82) and in 17 patients who received glucocorticoids alone (adjusted odds ratio, 0.54; 95% CI, 0.22 to 1.33). The adjusted odds ratios for a reduction in disease severity were similar in the two groups, as compared with IVIG alone (0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone). The time until a reduction in disease severity was similar in the three groups.CONCLUSIONSWe found n

Journal article

Osmanov IM, Spiridonova E, Bobkova P, Gamirova A, Shikhaleva A, Andreeva M, Blyuss O, El-Taravi Y, DunnGalvin A, Comberiati P, Peroni DG, Apfelbacher C, Genuneit J, Mazankova L, Miroshina A, Chistyakova E, Samitova E, Borzakova S, Bondarenko E, Korsunskiy AA, Konova I, Hanson SW, Carson G, Sigfrid L, Scott JT, Greenhawt M, Whittaker EA, Garralda E, Swann O, Buonsenso D, Nicholls DE, Simpson F, Jones C, Semple MG, Warner JO, Vos T, Olliaro P, Munblit D, Sechenov StopCOVID Research Teamet al., 2021, Risk factors for long covid in previoulsy hospitalsied children using the ISARIC Global Follow-Up Protocol: a prospective cohort study, European Respiratory Journal, ISSN: 0903-1936

Background The long-term sequelae of coronavirus disease 2019 (Covid-19) in children remain poorly characterised. This study aimed to assess long-term outcomes in children previously hospitalised with Covid-19 and associated risk factors.Methods This is a prospective cohort study of children (≤18 years old) admitted with confirmed Covid-19. Children admitted to the hospital between April 2, 2020 and August 26, 2020, were included. Telephone interview using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) Covid-19 Health and Wellbeing paediatric follow-up survey. Persistent symptoms (>5 months) were further categorised by system(s) involved.Findings 518 of 853 (61%) of eligible children were available for the follow-up assessment and included in the study. Median age was 10.4 years (IQR, 3–15.2) and 270 (52.1%) were girls; median follow-up since hospital discharge was 256 (223–271) days. At the time of the follow-up interview 126 (24.3%) participants reported persistent symptoms among which fatigue (53, 10.7%), sleep disturbance (36, 6.9%,) and sensory problems (29, 5.6%) were the most common. Multiple symptoms were experienced by 44 (8.4%) participants. Risk factors for persistent symptoms were: older age “6–11 years” (odds ratio 2.74 (95% confidence interval 1.37 to 5.75) and “12–18 years” (2.68, 1.41 to 5.4); and a history of allergic diseases (1.67, 1.04 to 2.67).Interpretation A quarter of children experienced persistent symptoms months after hospitalization with acute covid-19 infection, with almost one in ten experiencing multi-system involvement. Older age and allergic diseases were associated with higher risk of persistent symptoms at follow-up.

Journal article

Habermann S, Ferran E, Hatcher J, Lyall H, de la Fuente J, Whittaker Eet al., 2021, Outbreak of non-tuberculous mycobacteria in a paediatric bone marrow transplant unit associated with water contamination of needle-free connectors and literature review, BONE MARROW TRANSPLANTATION, ISSN: 0268-3369

Journal article

Schlapbach LJ, Andre MC, Grazioli S, Schobi N, Ritz N, Aebi C, Agyeman P, Albisetti M, Bailey DGN, Berger C, Blanchard-Rohner G, Bressieux-Degueldre S, Hofer M, L'Huillier AG, Marston M, Meyer Sauteur PM, Pachlopnik Schmid J, Perez M-H, Rogdo B, Truck J, Woerner A, Wutz D, Zimmermann P, Levin M, Whittaker E, Rimensberger PCet al., 2021, Best practice recommendations for the diagnosis and management of children with pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS; multisystem inflammatory syndrome in children, MIS-C) in Switzerland, Frontiers in Pediatrics, Vol: 9, Pages: 1-14, ISSN: 2296-2360

Background: Following the spread of the coronavirus disease 2019 (COVID-19) pandemic a new disease entity emerged, defined as Pediatric Inflammatory Multisystem Syndrome temporally associated with COVID-19 (PIMS-TS), or Multisystem Inflammatory Syndrome in Children (MIS-C). In the absence of trials, evidence for treatment remains scarce.Purpose: To develop best practice recommendations for the diagnosis and treatment of children with PIMS-TS in Switzerland. It is acknowledged that the field is changing rapidly, and regular revisions in the coming months are pre-planned as evidence is increasing.Methods: Consensus guidelines for best practice were established by a multidisciplinary group of Swiss pediatric clinicians with expertise in intensive care, immunology/rheumatology, infectious diseases, hematology, and cardiology. Subsequent to literature review, four working groups established draft recommendations which were subsequently adapted in a modified Delphi process. Recommendations had to reach >80% agreement for acceptance.Results: The group achieved agreement on 26 recommendations, which specify diagnostic approaches and interventions across anti-inflammatory, anti-infectious, and support therapies, and follow-up for children with suspected PIMS-TS. A management algorithm was derived to guide treatment depending on the phenotype of presentation, categorized into PIMS-TS with (a) shock, (b) Kawasaki-disease like, and (c) undifferentiated inflammatory presentation.Conclusion: Available literature on PIMS-TS is limited to retrospective or prospective observational studies. Informed by these cohort studies and indirect evidence from other inflammatory conditions in children and adults, as well as guidelines from international health authorities, the Swiss PIMS-TS recommendations represent best practice guidelines based on currently available knowledge to standardize treatment of children with suspected PIMS-TS. Given the absence of high-grade evidence, regular up

Journal article

Davies P, Lillie J, Prayle A, Evans C, Griffiths B, du Pre P, Johnson M, Kanthimathinathan HK, Playfor S, Deep A, Brierley J, Waters G, Mohammad Z, Singh D, Jardine M, Ross O, Shetty N, Worrall M, Sinha R, Koul A, Whittaker E, Vyas H, Ramnarayan P, Scholefield BRet al., 2021, Association between treatments and short-term biochemical improvements and clinical outcomes in post-severe acute respiratory syndrome Coronavirus-2 inflammatory syndrome, Pediatric Critical Care Medicine, Vol: 22, Pages: E282-E290, ISSN: 1529-7535

OBJECTIVES: To 1) analyze the short-term biochemical improvements and clinical outcomes following treatment of children with post-severe acute respiratory syndrome coronavirus-2 inflammatory syndrome (multisystem inflammatory syndrome in children/pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2) admitted to U.K. PICUs and 2) collate current treatment guidance from U.K. PICUs.DESIGN: Multicenter observational study.SETTING: Twenty-one U.K. PICUs.PATIENTS: Children (< 18 yr) admitted to U.K. PICUs between April 1, 2020, and May 10, 2020, fulfilling the U.K. case definition of pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2.INTERVENTIONS: None.MEASUREMENTS AND MAIN RESULTS: Routinely collected, deidentified data were analyzed. Propensity score and linear mixed effects models were used to analyze the effect of steroids, IV immunoglobulin, and biologic agents on changes in C-reactive protein, platelet counts, and lymphocyte counts over the course of PICU stay. Treatment recommendations from U.K. clinical guidelines were analyzed. Over the 6-week study period, 59 of 78 children (76%) received IV immunoglobulin, 57 of 78 (73%) steroids, and 18 of 78 (24%) a biologic agent. We found no evidence of a difference in response in clinical markers of inflammation between patients with multisystem inflammatory syndrome in children/pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 who were treated with IV immunoglobulin, steroids, or biologics, compared with those who were not. By the end of the study period, most patients had received immunomodulation. The 12 patients who did not receive any immunomodulators had similar decrease in inflammatory markers as those treated. Of the 14 guidelines analyzed, the use of IV immunoglobulin, steroids, and biologics was universally re

Journal article

Flood J, Shingleton J, Bennett E, Walker B, Amin-Chowdhury Z, Oligbu G, Avis J, Lynn RM, Davis P, Bharucha T, Pain CE, Jyothish D, Whittaker E, Dwarakanathan B, Wood R, Williams C, Swann O, Semple MG, Ramsay ME, Jones CE, Ramanan A, Gent N, Ladhani SNet al., 2021, Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS): Prospective, national surveillance, United Kingdom and Ireland, 2020, LANCET REGIONAL HEALTH-EUROPE, Vol: 3, Pages: 1-11, ISSN: 2666-7762

BackgroundPaediatric Multisystem Inflammatory Syndrome temporally associated with SARS-CoV-2 (PIMS-TS), first identified in April 2020, shares features of both Kawasaki disease (KD) and toxic shock syndrome (TSS). The surveillance describes the epidemiology and clinical characteristics of PIMS-TS in the United Kingdom and Ireland.MethodsPublic Health England initiated prospective national surveillance of PIMS-TS through the British Paediatric Surveillance Unit. Paediatricians were contacted monthly to report PIMS-TS, KD and TSS cases electronically and complete a detailed clinical questionnaire. Cases with symptom onset between 01 March and 15 June 2020 were included.FindingsThere were 216 cases with features of PIMS-TS alone, 13 with features of both PIMS-TS and KD, 28 with features of PIMS-TS and TSS and 11 with features of PIMS-TS, KD and TSS, with differences in age, ethnicity, clinical presentation and disease severity between the phenotypic groups. There was a strong geographical and temporal association between SARS-CoV-2 infection rates and PIMS-TS cases. Of those tested, 14.8% (39/264) children had a positive SARS-CoV-2 RT-PCR, and 63.6% (75/118) were positive for SARS-CoV-2 antibodies. In total 44·0% (118/268) required intensive care, which was more common in cases with a TSS phenotype. Three of five children with cardiac arrest had TSS phenotype. Three children (1·1%) died.InterpretationThe strong association between SARS-CoV-2 infection and PIMS-TS emphasises the importance of maintaining low community infection rates to reduce the risk of this rare but severe complication in children and adolescents. Close follow-up will be important to monitor long-term complications in children with PIMS-TS.FundingPHE.

Journal article

Whittaker E, Sinha R, 2021, COVID-19; lessons learned from a paediatric high consequence infectious diseases (HCID) unit, Archives of Disease in Childhood, Vol: 106, ISSN: 0003-9888

In 2018, NHS England commissioned 4 airborne high consequence infectious diseases (HCID) units which could take adults and children in preparation for the emergence of a new airborne viral infection in the UK. St Mary’s Hospital (Imperial College Healthcare NHS Trust), London was one of the paediatric centres, partnered with the Royal Free Hospital for adults. St Mary’s was ideally placed to look after children with possible airborne HCID, with a newly designed and built suite of HCID rooms and an expert and collaborative group of paediatric intensivists and infectious diseases consultants. It was exciting to prepare for these eventualities, which felt unlikely as we focussed instead on Brexit and the environment. In retrospect, we are ashamed of thinking that this would be exciting, as we now live through a pandemic whose proportions go well beyond our wildest nightmares.

Journal article

Jan W, Jones B, Jeelani NUO, Jacques TS, Lyall H, Randell P, Mewasingh L, Whittaker Eet al., 2021, Acute flaccid myelitis caused by enterovirus D68 unmasking primary intracranial tumour in a previously healthy child, JOURNAL OF PAEDIATRICS AND CHILD HEALTH, ISSN: 1034-4810

Journal article

Harwood R, Allin B, Jones CE, Whittaker E, Ramnarayan P, Ramanan A, Kaleem M, Tulloh R, Peters MJ, Almond S, Davis PJ, Levin M, Tometzki A, Faust SN, Knight M, Kenny Set al., 2021, A national consensus management pathway for paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS): results of a national Delphi process, LANCET CHILD & ADOLESCENT HEALTH, Vol: 5, Pages: 133-141, ISSN: 2352-4642

Journal article

Park M, Dhawan R, Whittaker E, Kon OMet al., 2021, CA 125 and TB, BMJ CASE REPORTS, Vol: 14

Journal article

Viner RM, Ward JL, Hudson LD, Ashe M, Patel SV, Hargreaves D, Whittaker Eet al., 2020, Systematic review of reviews of symptoms and signs of COVID-19 in children and adolescents, Archives of Disease in Childhood, ISSN: 0003-9888

OBJECTIVE: To undertake a systematic review of reviews of the prevalence of symptoms and signs of COVID-19 in those aged under 20 years. DESIGN: Narrative systematic review of reviews. PubMed, medRxiv, Europe PMC and COVID-19 Living Evidence Database were searched on 9 October 2020. SETTING: All settings, including hospitalised and community settings. PATIENTS: Children and young people (CYP) under age 20 years with laboratory-proven COVID-19. STUDY REVIEW, DATA EXTRACTION AND QUALITY: Potentially eligible articles were reviewed on title and abstract by one reviewer. Quality was assessed using the modified AMSTARS criteria and data were extracted from included studies by two reviewers. MAIN OUTCOME MEASURES: Prevalence of symptoms and signs of COVID-19. RESULTS: 1325 studies were identified and 18 reviews were included. Eight were high quality, 7 medium and 3 low quality. All reviews were dominated by studies of hospitalised children. The proportion of asymptomatic CYP ranged from 14.6% to 42%. Fever and cough were the the most common symptoms; proportions with fever ranged from 46% to 64.2% and with cough from 32% to 55.9%. All other symptoms or signs including rhinorrhoea, sore throat, headache, fatigue/myalgia and gastrointestinal symptoms including diarrhoea and vomiting were infrequent, occurring in less than 10%-20%. CONCLUSIONS: Fever and cough are the most common symptoms in CYP with COVID-19, with other symptoms infrequent. Further research on symptoms in community samples are needed to inform pragmatic identification and testing programmes for CYP.

Journal article

Bogiatzopoulou A, Mayberry H, Hawcutt DB, Whittaker E, Munro A, Roland D, Simba J, Gale C, Felsenstein S, Abrams E, Jones CB, Lewins I, Rodriguez-Martinez CR, Fernandes RM, Stilwell PA, Swann O, Bhopal S, Sinha I, Harwood Ret al., 2020, COVID-19 in children: what did we learn from the first wave?, Paediatrics and Child Health, Vol: 30, Pages: 438-443, ISSN: 1751-7222

A pandemic caused by the novel coronavirus, severe acute respiratory syndrome - coronavirus 2 (SARS-CoV-2), has caused high rates of mortality, predominantly in adults. Children are significantly less affected by SARS-CoV-2 with far lower rates of recorded infections in children compared to adults, milder symptoms in the majority of children and very low mortality rates. A suspected late manifestation of the disease, paediatric inflammatory multisystem syndrome - temporally associated with SARS-CoV-2 (PIMS-TS), has been seen in small numbers of children and has a more severe disease course than acute SARS-CoV-2. The pandemic has meant that children around the world have been kept off school, isolated from their extended family and friends and asked to stay inside. The UK has just been declared as being in an economic recession and unemployment rates are increasing. These indirect effects of SARS-CoV-2 are likely to have a significant impact on many children for years to come. Consolidating the knowledge that has accumulated during the first wave of this pandemic is essential for recognising the clinical signs, symptoms and effective treatment strategies for children; identifying children who may be at increased risk of severe SARS-CoV-2 infection; planning the safe delivery of healthcare and non-health related services that are important for childrens’ wellbeing; and engaging in, and developing, research to address the things that are not yet known. This article summarises the evidence that has emerged from the early phase of the pandemic and offers an overview for those looking after children or planning services.

Journal article

Altamar IB, Whittaker E, Herberg J, Fraisse A, Bautista C, Kang H, Giselle R, Wage R, Lane M, Piccinelli E, Di Salvo G, Mohiaddin R, Pennell DJ, Krupickova SJet al., 2020, Short-term Sequalae of Children With Paediatric Inflammatory Multisystem Syndrome Temporarily Associated With Sars-cov-2 Infection (pims-ts) Assessed by Cardiovascular Magnetic Resonance, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0009-7322

Conference paper

Yeo KT, Oei JL, De Luca D, Schmölzer GM, Guaran R, Palasanthiran P, Kumar K, Buonocore G, Cheong J, Owen LS, Kusuda S, James J, Lim G, Sharma A, Uthaya S, Gale C, Whittaker E, Battersby C, Modi N, Norman M, Naver L, Giannoni E, Diambomba Y, Shah PS, Gagliardi L, Harrison M, Pillay S, Alburaey A, Yuan Y, Zhang Het al., 2020, Review of guidelines and recommendations from 17 countries highlights the challenges that clinicians face caring for neonates born to mothers with COVID-19., Acta Paediatrica: Nurturing the Child, Vol: 109, Pages: 2192-2207, ISSN: 1651-2227

AIM: This review examined how applicable national and regional clinical practice guidelines and recommendations for managing neonates born to mothers with COVID-19 mothers were to the evolving pandemic. METHODS: A systematic search and review identified 20 guidelines and recommendations that had been published by 25 May 2020. We analysed documents from 17 countries: Australia, Brazil, Canada, China, France, India, Italy, Japan, Saudi Arabia, Singapore, South Africa, South Korea, Spain, Sweden, Switzerland, the UK and the USA. RESULTS: The documents were based on expert consensus with limited evidence and were of variable, low methodological rigour. Most did not provide recommendations for delivery methods or managing symptomatic infants. None provided recommendations for post-discharge assimilation of potentially-infected infants into the community. The majority encouraged keeping mothers and infants together, subject to infection control measures, but one-third recommended separation. Although breastfeeding or using breastmilk were widely encouraged, two countries specifically prohibited this. CONCLUSION: The guidelines and recommendations for managing infants affected by COVID-19 were of low, variable quality and may be unsustainable. It is important that transmission risks are not increased when new information is incorporated into clinical recommendations. Practice guidelines should emphasise the extent of uncertainty and clearly define gaps in the evidence.

Journal article

Mitting R, Rajagopol V, Grossman T, Whittaker E, Chalker V, Lai S, Hoffman P, Atkin S, Qureshi S, Hatcher Jet al., 2020, Severe neonatal legionellosis associated with use of home humidifiers – A case report, Clinical Infection in Practice, Vol: 7-8, Pages: 1-3, ISSN: 2590-1702

Neonatal Legionella pneumophila infection is rare and mortality is high. There has been limited success with the use of extracorporeal membrane oxygenation, with reported mortality in infants of 88%. We present the case of a 5 day old infant with neonatal legionellosis who had been exposed to cold mist humidifiers in the home, filled from a domestic water supply contaminated with legionella. The infant was treated with veno-arterial extracorporeal membrane oxygenation and survived with subsequently normal neurodevelopmental follow-up. In view of the rapid growth of the worldwide humidifier market, the association between neonatal legionella and use of cold mist humidification may be important. Consideration of legionellosis should be given for any neonate presenting with severe sepsis or respiratory compromise who has been exposed to aerosol generating home humidifiers. In spite of previously reported high mortality in infants, this case demonstrates that excellent outcome is possible with early escalation to VA ECMO.

Journal article

Rodriguez-Martinez CE, Sinha IP, Whittaker E, Nagakumar P, Fernandes RMet al., 2020, Nebulization procedures for children with unknown viral status during the COVID-19 pandemic, JOURNAL OF ASTHMA, ISSN: 0277-0903

Journal article

Park M, Owles H, Williams A, Williams B, Whittaker E, Kon OMet al., 2020, PEDIATRIC ENDOBRONCHIAL ULTRASOUNDTRANSBRONCHIALNEEDLE ASPIRATION UNDERCONSCIOUS SEDATION FOR SUSPECTEDTUBERCULOSIS IN LONDON, Paediatric infectious diseases journal

Journal article

Davies P, Evans C, Kanthimathinathan HK, Lillie J, Brierley J, Waters G, Johnson M, Griffiths B, du Pre P, Mohammad Z, Deep A, Playfor S, Singh D, Inwald D, Jardine M, Ross O, Shetty N, Worrall M, Sinha R, Koul A, Whittaker E, Vyas H, Scholefield BR, Ramnarayan Pet al., 2020, Intensive care admissions of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the UK: a multicentre observational study, The Lancet Child and Adolescent Health, Vol: 4, Pages: 669-677, ISSN: 2352-4642

BackgroundIn April, 2020, clinicians in the UK observed a cluster of children with unexplained inflammation requiring admission to paediatric intensive care units (PICUs). We aimed to describe the clinical characteristics, course, management, and outcomes of patients admitted to PICUs with this condition, which is now known as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS).MethodsWe did a multicentre observational study of children (aged <18 years), admitted to PICUs in the UK between April 1 and May 10, 2020, fulfilling the case definition of PIMS-TS published by the Royal College of Paediatrics and Child Health. We analysed routinely collected, de-identified data, including demographic details, presenting clinical features, underlying comorbidities, laboratory markers, echocardiographic findings, interventions, treatments, and outcomes; serology information was collected if available. PICU admission rates of PIMS-TS were compared with historical trends of PICU admissions for four similar inflammatory conditions (Kawasaki disease, toxic shock syndrome, haemophagocytic lymphohistiocytosis, and macrophage activation syndrome).Findings78 cases of PIMS-TS were reported by 21 of 23 PICUs in the UK. Historical data for similar inflammatory conditions showed a mean of one (95% CI 0·85–1·22) admission per week, compared to an average of 14 admissions per week for PIMS-TS and a peak of 32 admissions per week during the study period. The median age of patients was 11 years (IQR 8–14). Male patients (52 [67%] of 78) and those from ethnic minority backgrounds (61 [78%] of 78) were over-represented. Fever (78 [100%] patients), shock (68 [87%]), abdominal pain (48 [62%]), vomiting (49 [63%]), and diarrhoea (50 [64%]) were common presenting features. Longitudinal data over the first 4 days of admission showed a serial reduction in C-reactive protein (from a median of 264 mg/L on day 1 to 96 mg/L on day 4)

Journal article

Götzinger F, Santiago-García B, Noguera-Julián A, Lanaspa M, Lancella L, Calò Carducci FI, Gabrovska N, Velizarova S, Prunk P, Osterman V, Krivec U, Lo Vecchio A, Shingadia D, Soriano-Arandes A, Melendo S, Lanari M, Pierantoni L, Wagner N, L'Huillier AG, Heininger U, Ritz N, Bandi S, Krajcar N, Roglić S, Santos M, Christiaens C, Creuven M, Buonsenso D, Welch SB, Bogyi M, Brinkmann F, Tebruegge M, Pfefferle J, Zacharasiewicz A, Berger A, Berger R, Strenger V, Kohlfürst DS, Zschocke A, Bernar B, Simma B, Haberlandt E, Thir C, Biebl A, Vanden Driessche K, Boiy T, Van Brusselen D, Bael A, Debulpaep S, Schelstraete P, Pavic I, Nygaard U, Glenthoej JP, Heilmann Jensen L, Lind I, Tistsenko M, Uustalu Ü, Buchtala L, Thee S, Kobbe R, Rau C, Schwerk N, Barker M, Tsolia M, Eleftheriou I, Gavin P, Kozdoba O, Zsigmond B, Valentini P, Ivaškeviciene I, Ivaškevicius R, Vilc V, Schölvinck E, Rojahn A, Smyrnaios A, Klingenberg C, Carvalho I, Ribeiro A, Starshinova A, Solovic I, Falcón L, Neth O, Minguell L, Bustillo M, Gutiérrez-Sánchez AM, Guarch Ibáñez B, Ripoll F, Soto B, Kötz K, Zimmermann P, Schmid H, Zucol F, Niederer A, Buettcher M, Cetin BS, Bilogortseva O, Chechenyeva V, Demirjian A, Shackley F, McFetridge L, Speirs L, Doherty C, Jones L, McMaster P, Murray C, Child F, Beuvink Y, Makwana N, Whittaker E, Williams A, Fidler K, Bernatoniene J, Song R, Oliver Z, Riordan Aet al., 2020, COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study, The Lancet Child and Adolescent Health, Vol: 4, Pages: 653-661, ISSN: 2352-4642

BackgroundTo date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic.MethodsThis multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network—the Paediatric Tuberculosis Network European Trials Group (ptbnet)—that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission.Findings582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5–12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2–11, range 1–34), 19 (3%) inotropic support, and one (<1%) extracorporeal membrane oxygenation. Significant risk factors for requiring ICU admission in multivariable analyses were being younger than 1 month (odds ratio 5·06, 95% CI 1·72–14·87; p=0·0035), male sex (2·12, 1·06–4·21; p=0·033), p

Journal article

Whittaker E, Bamford A, Kenny J, Kaforou M, Jones CE, Shah P, Ramnarayan P, Fraisse A, Miller O, Davies P, Kucera F, Brierley J, McDougall M, Carter M, Tremoulet A, Shimizu C, Herberg J, Burns JC, Lyall H, Levin Met al., 2020, Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2, JAMA, Vol: 324, Pages: 259-269, ISSN: 0098-7484

Importance In communities with high rates of coronavirus disease 2019, reports have emerged of children with an unusual syndrome of fever and inflammation.Objectives To describe the clinical and laboratory characteristics of hospitalized children who met criteria for the pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PIMS-TS) and compare these characteristics with other pediatric inflammatory disorders.Design, Setting, and Participants Case series of 58 children from 8 hospitals in England admitted between March 23 and May 16, 2020, with persistent fever and laboratory evidence of inflammation meeting published definitions for PIMS-TS. The final date of follow-up was May 22, 2020. Clinical and laboratory characteristics were abstracted by medical record review, and were compared with clinical characteristics of patients with Kawasaki disease (KD) (n = 1132), KD shock syndrome (n = 45), and toxic shock syndrome (n = 37) who had been admitted to hospitals in Europe and the US from 2002 to 2019.Exposures Signs and symptoms and laboratory and imaging findings of children who met definitional criteria for PIMS-TS from the UK, the US, and World Health Organization.Main Outcomes and Measures Clinical, laboratory, and imaging characteristics of children meeting definitional criteria for PIMS-TS, and comparison with the characteristics of other pediatric inflammatory disorders.Results Fifty-eight children (median age, 9 years [interquartile range {IQR}, 5.7-14]; 33 girls [57%]) were identified who met the criteria for PIMS-TS. Results from SARS-CoV-2 polymerase chain reaction tests were positive in 15 of 58 patients (26%) and SARS-CoV-2 IgG test results were positive in 40 of 46 (87%). In total, 45 of 58 patients (78%) had evidence of current or prior SARS-CoV-2 infection. All children presented with fever and nonspecific symptoms, including v

Journal article

Frauenfelder C, Brierley J, Whittaker E, Perucca G, Bamford Aet al., 2020, Infant with SARS-CoV-2 infection causing severe lung disease treated with remdesivir, Pediatrics, ISSN: 0031-4005

We describe an ex-premature infant presenting with SARS-CoV-2 infection in the 5th week oflife. Current reports indicate that acute symptomatic SARS-CoV-2 infection is relatively rare andmuch less severe than in adults. This case highlights that infection can be associated with lifethreatening pulmonary disease in young infants and that infection can follow a similar diseasecourse to that described in adults. We provide first data on the use of the novel antiviralremdesivir in a young child and an innovative approach to expedited approval from amultidisciplinary clinical team and bioethics committee for compassionate access to the drug.

Journal article

Viner RM, Whittaker E, 2020, Kawasaki-like disease: emerging complication during the COVID-19 pandemic., The Lancet, Vol: 395, Pages: 1741-1743, ISSN: 0140-6736

Journal article

Kadambari S, Whittaker E, Lyall H, 2020, Postnatally acquired cytomegalovirus infection in extremely premature infants: how best to manage?, ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION, Vol: 105, Pages: F334-F339, ISSN: 1359-2998

Journal article

Ferreras-Antolin L, Irwin A, Atra A, Dermirjian A, Drysdale SB, Emonts M, McMaster P, Paulus S, Patel S, Kinsey S, Vergnano S, Whittaker E, Warris Aet al., 2019, Neonatal Antifungal Consumption Is Dominated by Prophylactic Use; Outcomes From The Pediatric Antifungal Stewardship: Optimizing Antifungal Prescription Study, PEDIATRIC INFECTIOUS DISEASE JOURNAL, Vol: 38, Pages: 1219-1223, ISSN: 0891-3668

Journal article

Owles H, Park M, Whittaker E, Williams A, Williams B, Kon OMet al., 2019, EBUS-TBNA in a paediatric population in London, European-Respiratory-Society (ERS) International Congress, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Seddon J, Whittaker E, Kampmann B, Lewinsohn D, Osman M, Hesseling A, Rustomjee R, Amanullah Fet al., 2019, The evolving research agenda for paediatric tuberculosis infection, Lancet Infectious Diseases, Vol: 19, Pages: e323-e329, ISSN: 1473-3099

Following exposure to tuberculosis and subsequent infection, children often progress to tuberculosis disease more rapidly than adults. And yet the natural history of tuberculosis in children, as a continuum from exposure to infection and then to disease, is poorly understood. Children are rarely diagnosed with tuberculosis infection in routine care in international settings and few receive tuberculosis infection treatment. In this Personal View, we review the most up-to-date knowledge in three areas of childhood tuberculosis infection—namely, pathophysiology, diagnosis, and treatment. We then outline what is missing in each of these three areas to generate a priority research agenda. Finally, we suggest potential study designs that might answer these questions. Understanding of pathophysiology could be improved through animal models, laboratory studies assessing the immunological responses of blood or respiratory samples to Mycobacterium spp in vitro, as well as investigating immune responses in children exposed to tuberculosis. Identification of children with sub-clinical disease and at high risk of progression to clinically overt disease, would allow treatment to be targeted at those most likely to benefit. Optimisation and discovery of novel treatments for tuberculosis infection in children should account for mechanisms of action of tuberculosis drugs, as well as child-specific factors including pharmacokinetics and appropriate formulations. To conduct these studies, a change in mindset is required, with a recognition that the diagnosis and treatment of tuberculosis infection in children is a necessary component in addressing the overall tuberculosis epidemic. Collaboration between stakeholders will be required and funding will need to increase, both for research and implementation. The consequences of inaction, however, will lead to further decades of children suffering from what should increasingly be recognised as a preventable disease.

Journal article

Whittaker E, Lopez-Varela E, Broderick C, Seddon Jet al., 2019, Examining the complex relationship between tuberculosis and other infectious diseases in children: a review, Frontiers in Pediatrics, Vol: 7, Pages: 1-23, ISSN: 2296-2360

Millions of children are exposed to tuberculosis (TB) each year, many of which become infected with Mycobacterium tuberculosis. Most children can immunologically contain or eradicate the organism without pathology developing. However, in a minority, the organism overcomes the immunological constraints, proliferates and causes TB disease. Each year a million children develop TB disease, with a quarter dying. While it is known that young children and those with immunodeficiencies are at increased risk of progression from TB infection to TB disease, our understanding of risk factors for this transition is limited. The most immunologically disruptive process that can happen during childhood is infection with another pathogen and yet the impact of co-infections on TB risk is poorly investigated. Many diseases have overlapping geographical distributions to TB and affect similar patient populations. It is therefore likely that infection with viruses, bacteria, fungi and protozoa may impact on the risk of developing TB disease following exposure and infection, although disentangling correlation and causation is challenging. As vaccinations also disrupt immunological pathways, these may also impact on TB risk. In this article we describe the paediatric immune response to M. tuberculosis and then review the existing evidence of the impact of co-infection with other pathogens, as well as vaccination, on the host response to M. tuberculosis. We focus on the impact of other organisms on the risk of TB disease in children, in particularly evaluating if co-infections drive host immune responses in an age-dependent way. The pathology seen in young children is primarily the result of an insufficient and inadequate response, while the pathology seen in adolescents and adults reflects an over-exuberant response, leading to host tissue damage. We will explore if co-infections drive the host response in these directions. We finally propose priorities for future research in this field. A

Journal article

Basu Roy R, Whittaker E, Seddon JA, Kampmann Bet al., 2019, Tuberculosis susceptibility and protection in children, Lancet Infectious Diseases, Vol: 19, Pages: e96-e108, ISSN: 1473-3099

Children represent both a clinically important population susceptible to tuberculosis and a key group in whom to study intrinsic and vaccine-induced mechanisms of protection. After exposure to Mycobacterium tuberculosis, children aged under 5 years are at high risk of progressing first to tuberculosis infection, then to tuberculosis disease and possibly disseminated forms of tuberculosis, with accompanying high risks of morbidity and mortality. Children aged 5–10 years are somewhat protected, until risk increases again in adolescence. Furthermore, neonatal BCG programmes show the clearest proven benefit of vaccination against tuberculosis. Case-control comparisons from key cohorts, which recruited more than 15 000 children and adolescents in total, have identified that the ratio of monocytes to lymphocytes, activated CD4 T cell count, and a blood RNA signature could be correlates of risk for developing tuberculosis. Further studies of protected and susceptible populations are necessary to guide development of novel tuberculosis vaccines that could facilitate the achievement of WHO's goal to eliminate deaths from tuberculosis in childhood.

Journal article

Whittaker E, Chellen S, Eisenhut M, Grandjean Let al., 2018, Cerebral tuberculomas in a 6-year-old girl causing central diabetes insipidus, BMJ Case Reports, Vol: 2018, ISSN: 1757-790X

A 6-year-old girl presented acutely with worsening frontal headaches. She had a 3-month history of lethargy, reduced appetite, weight loss, cough and intermittent fevers. A chest X-ray showed a left upper lobe consolidation, and a CT head showed multiple enhancing lesions with significant surrounding oedema in both cerebral hemispheres. Due to the strong suspicion of tuberculosis (TB), she was admitted and treated with anti-TB therapy and steroids. Following this, pulmonary infection with Mycobacterium tuberculosis was confirmed by a positive PCR from induced sputum. Cerebral spinal fluid (CSF) analysis was normal and tested negative for M. tuberculosis on PCR. During her first week of treatment, she developed polyuria, nocturia and polydipsia and was diagnosed with central diabetes insipidus. She was started on desmopressin which rapidly improved her symptoms, and she was continued on desmopressin for 3 months. Currently, she remains well and has shown a good response to TB treatment.

Journal article

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