Imperial College London

Dr James A Seddon

Faculty of MedicineDepartment of Infectious Disease

Reader in Global Child Health
 
 
 
//

Contact

 

+44 (0)20 7594 3179james.seddon

 
 
//

Location

 

235Norfolk PlaceSt Mary's Campus

//

Summary

 

Publications

Publication Type
Year
to

190 results found

Marcy O, Wobudeya E, Font H, Vessière A, Chabala C, Khosa C, Taguebue J-V, Moh R, Mwanga-Amumpaire J, Lounnas M, Mulenga V, Mavale S, Chilundo J, Rego D, Nduna B, Shankalala P, Chirwa U, De Lauzanne A, Dim B, Tiogouo Ngouana E, Folquet Amorrissani M, Cisse L, Amon Tanoh Dick F, Komena EA, Kwedi Nolna S, Businge G, Natukunda N, Cumbe S, Mbekeka P, Kim A, Kheang C, Pol S, Maleche-Obimbo E, Seddon JA, Mao TE, Graham SM, Delacourt C, Borand L, Bonnet M, TB-Speed Pneumonia Study Groupet al., 2022, Effect of systematic tuberculosis detection on mortality in young children with severe pneumonia in countries with high incidence of tuberculosis: a stepped-wedge cluster-randomised trial., Lancet Infect Dis

BACKGROUND: Tuberculosis diagnosis might be delayed or missed in children with severe pneumonia because this diagnosis is usually only considered in cases of prolonged symptoms or antibiotic failure. Systematic tuberculosis detection at hospital admission could increase case detection and reduce mortality. METHODS: We did a stepped-wedge cluster-randomised trial in 16 hospitals from six countries (Cambodia, Cameroon, Côte d'Ivoire, Mozambique, Uganda, and Zambia) with high incidence of tuberculosis. Children younger than 5 years with WHO-defined severe pneumonia received either the standard of care (control group) or standard of care plus Xpert MTB/RIF Ultra (Xpert Ultra; Cepheid, Sunnyvale, CA, USA) on nasopharyngeal aspirate and stool samples (intervention group). Clusters (hospitals) were progressively switched from control to intervention at 5-week intervals, using a computer-generated random sequence, stratified on incidence rate of tuberculosis at country level, and masked to teams until 5 weeks before switch. We assessed the effect of the intervention on primary (12-week all-cause mortality) and secondary (including tuberculosis diagnosis) outcomes, using generalised linear mixed models. The primary analysis was by intention to treat. We described outcomes in children with severe acute malnutrition in a post hoc analysis. This study is registered with ClinicalTrials.gov (NCT03831906) and the Pan African Clinical Trial Registry (PACTR202101615120643). FINDINGS: From March 21, 2019, to March 30, 2021, we enrolled 1401 children in the control group and 1169 children in the intervention group. In the intervention group, 1140 (97·5%) children had nasopharyngeal aspirates and 942 (80·6%) had their stool collected; 24 (2·1%) had positive Xpert Ultra. At 12 weeks, 110 (7·9%) children in the control group and 91 (7·8%) children in the intervention group had died (adjusted odds ratio [OR] 0·986, 95% CI 0·597-1&midd

Journal article

Garcia-Prats AJ, Starke JR, Waning B, Kaiser B, Seddon JAet al., 2022, New Drugs and Regimens for Tuberculosis Disease Treatment in Children and Adolescents, JOURNAL OF THE PEDIATRIC INFECTIOUS DISEASES SOCIETY, Vol: 11, Pages: S101-S109, ISSN: 2048-7193

Journal article

van wyk S, Nliwasa M, Seddon J, Hoddinott G, Nepolo E, Gunther G, Lin H, Niemann S, Gandhi N, Shah S, Claassens Met al., 2022, Drug-resistant tuberculosis case-finding strategies: a scoping review protocol, JMIR Research Protocols, ISSN: 1929-0748

Journal article

Ranasinghe L, Achar J, Groschel M, Whittaker E, Dodd P, Seddon Jet al., 2022, The global impact of COVID-19 on childhood tuberculosis: analysis of notification data, The Lancet Global Health, ISSN: 2214-109X

Background:There is concern that the Coronavirus Disease-19 (COVID-19) pandemic has damaged global childhood tuberculosis management. Quantifying changes in child tuberculosis notifications could support more targeted interventions to restore child tuberculosis services.Methods: Annual case notification data reported to the World Health Organization (WHO) by 215 countries were used to calculate annual notification counts for 2014-2020 stratified by age groups (0-4, 5-14 and 15+ years) and sex. We used time series modelling to predict notification counts for 2020, and calculated differences from observed 2020 notifications at WHO region level and country-level for the 30 high tuberculosis-burden countries. We assessed association between these differences and the Oxford Government Response Tracker, a measure of COVID-19 social impact. Findings:Before 2020, annual notification counts increased across all age groups and WHO regions. More males than females 0-4 years were notified in all years and WHO regions. In 2020, global notifications for children 0-4 years were 35.4% lower than predicted (95% prediction interval [PI] -30.3 to -39.9), compared to 27.7% lower (95% PI: -23.4 to -31.5) in children 5-14 years and 18.8% lower (95%PI; -15.4 to -21.9) in 15+ years. The difference between predicted and observed notifications for 2020 were greater in males (-30.9%; 95%PI: -24.8 to -36.1) than females (-24.5%; 95%PI: -18.1 to –29.9%). No association was seen between severity of COVID-19 restrictions and change in notifications.Interpretation:Our findings suggest that COVID-19 has substantially impacted child tuberculosis services with the youngest children most affected. Although children suffered fewer severe health consequences from COVID-19 infection, they have been disproportionately affected by the consequences of the pandemic on tuberculosis care. As countries rebuild health systems post-COVID-19, it is vital that childhood tuberculosis services are placed centr

Journal article

Solomons RS, van Toorn R, Cresswell FV, Seddon JAet al., 2022, Update on the Treatment of Pediatric Tuberculous Meningitis, PEDIATRIC INFECTIOUS DISEASE JOURNAL, Vol: 41, Pages: E393-E395, ISSN: 0891-3668

Journal article

Martinez L, Cords O, Liu Q, Acuna-Villaorduna C, Bonnet M, Fox GJ, Carvalho ACC, Chan P-C, Croda J, Hill PC, Lopez-Varela E, Donkor S, Fielding K, Graham SM, Espinal MA, Kampmann B, Reingold A, Huerga H, Villalba JA, Grandjean L, Sotgiu G, Egere U, Singh S, Zhu L, Lienhardt C, Denholm JT, Seddon JA, Whalen CC, García-Basteiro AL, Triasih R, Chen C, Singh J, Huang L-M, Sharma S, Hannoun D, Del Corral H, Mandalakas AM, Malone LL, Ling D-L, Kritski A, Stein CM, Vashishtha R, Boulahbal F, Fang C-T, Boom WH, Netto EM, Lemos AC, Hesseling AC, Kay A, Jones-López EC, Horsburgh CR, Lange C, Andrews JRet al., 2022, Infant BCG vaccination and risk of pulmonary and extrapulmonary tuberculosis throughout the life course: a systematic review and individual participant data meta-analysis., Lancet Glob Health, Vol: 10, Pages: e1307-e1316

BACKGROUND: BCG vaccines are given to more than 100 million children every year, but there is considerable debate regarding the effectiveness of BCG vaccination in preventing tuberculosis and death, particularly among older children and adults. We therefore aimed to investigate the age-specific impact of infant BCG vaccination on tuberculosis (pulmonary and extrapulmonary) development and mortality. METHODS: In this systematic review and individual participant data meta-analysis, we searched MEDLINE, Web of Science, BIOSIS, and Embase without language restrictions for case-contact cohort studies of tuberculosis contacts published between Jan 1, 1998, and April 7, 2018. Search terms included "mycobacterium tuberculosis", "TB", "tuberculosis", and "contact". We excluded cohort studies that did not provide information on BCG vaccination or were done in countries that did not recommend BCG vaccination at birth. Individual-level participant data for a prespecified list of variables, including the characteristics of the exposed participant (contact), the index case, and the environment, were requested from authors of all eligible studies. Our primary outcome was a composite of prevalent (diagnosed at or within 90 days of baseline) and incident (diagnosed more than 90 days after baseline) tuberculosis in contacts exposed to tuberculosis. Secondary outcomes were pulmonary tuberculosis, extrapulmonary tuberculosis, and mortality. We derived adjusted odds ratios (aORs) using mixed-effects, binary, multivariable logistic regression analyses with study-level random effects, adjusting for the variable of interest, baseline age, sex, previous tuberculosis, and whether data were collected prospectively or retrospectively. We stratified our results by contact age and Mycobacterium tuberculosis infection status. This study is registered with PROSPERO, CRD42020180512. FINDINGS: We identified 14 927 original records from our database searches. W

Journal article

Cardoso Pinto A, Ranasinghe L, Dodd P, Budhathoki SS, Seddon J, Whittaker Eet al., 2022, Disruptions to routine childhood vaccinations in low- and middle-Income countries during the COVID-19 pandemic: a systematic review, Frontiers in Pediatrics, Vol: 10, ISSN: 2296-2360

BackgroundThe COVID-19 pandemic has disrupted routine childhood vaccinations worldwide with low- and middle-income countries (LMICs) most affected. This study aims to quantify levels of disruption to routine vaccinations in LMICs. MethodsA systematic review (PROSPERO CRD42021286386) was conducted of MEDLINE, Embase, Global Health, CINAHL, Scopus and MedRxiv, on the 11th of February 2022. Primary research studies published from January 2020 onwards were included if they reported levels of routine paediatric vaccinations before and after March 2020. Study appraisal was performed using NHLBI tool for cross-sectional studies. Levels of disruption were summarised using medians and interquartile ranges. ResultsA total of 39 cross-sectional studies were identified. These showed an overall relative median decline of 10.8% (interquartile range [IQR] -27.6%, -1.4%) across all vaccines. Upper-middle-income countries (upper-MICs) (-14.3%; IQR -24.3%, -2.4%) and lower-MICs (-18.0%; IQR 48.6%, 4.1%) showed greater declines than low-income countries (-3.1%; IQR -12.8%, 2.9%), as did vaccines administered at birth (-11.8%; IQR -27.7%, -3.5%) compared to those given after birth (-8.0%; IQR -28.6%, -0.4%). Declines during the first three months of the pandemic ( 8.1%; IQR -35.1%, -1.4%) were greater than during the remainder of 2020 (-3.9%; IQR 13.0%, 11.4%) compared to baseline. ConclusionThere has been a decline in routine paediatric vaccination, greatest in MICs and for vaccines administered at birth. Nations must prioritise catch-up programmes alongside public health messaging to encourage vaccine uptake.

Journal article

Nel Van Zyl K, Whitelaw A, Hesseling A, Seddon J, Demers A, Newton-Foot Met al., 2022, Fungal diversity in the gut microbiome of young South African children, BMC Microbiology, ISSN: 1471-2180

Background. The fungal microbiome, or mycobiome, is a poorly described component of the gut ecosystem and little is known about its structure and development in children. In South Africa, there have been no culture-independent evaluations of the child gut mycobiota. This study aimed to characterise the gut mycobiota and explore the relationships between fungi and bacteria in the gut microbiome of children from Cape Town communities. Methods. Stool samples were collected from children enrolled in the TB-CHAMP clinical trial. Internal transcribed spacer 1 (ITS1) gene sequencing was performed on a total of 115 stool samples using the Illumina MiSeq platform. Differences in fungal diversity and composition in relation to demographic, clinical, and environmental factors were investigated, and correlations between fungi and previously described bacterial populations in the same samples were described.Results. Taxa from the genera Candida and Saccharomyces were detected in all participants. Differential abundance analysis showed that Candida spp. were significantly more abundant in children younger than 2 years compared to older children. The gut mycobiota was less diverse than the bacterial microbiota of the same participants, consistent with the findings of other human microbiome studies. The variation in richness and evenness of fungi was substantial, even between individuals of the same age. There was significant association between vitamin A supplementation and higher fungal alpha diversity (p = 0.047), and girls were shown to have lower fungal alpha diversity (p = 0.003). Co-occurrence between several bacterial taxa and Candida albicans was observed.Conclusions. The dominant fungal taxa in our study population were similar to those reported in other paediatric studies; however, it remains difficult to identify the true core gut mycobiota due to the challenges set by the low abundance of gut fungi and the lack of true gut colonising species. The connection between the

Journal article

Wademan D, Goddinott G, Purchase S, Seddon J, Hesseling A, Garcia-Prats A, Reis R, Reynolds Let al., 2022, Practical and psychosocial challenges faced by caregivers influence the acceptability of multidrug-resistant tuberculosis preventive therapy for young children, PLoS One, Vol: 17, Pages: 1-18, ISSN: 1932-6203

Drug-resistant (DR) strains of Mycobacterium tuberculosis (M. tb) are increasingly recognised as a threat to global tuberculosis (TB) control efforts. Identifying people with DR-TB exposure/ infection and providing TB preventive therapy (TPT) is a public health priority. TB guidelines advise the evaluation of household contacts of newly diagnosed TB cases, with the provision of TPT to vulnerable populations, including young children (<5 years). Many children become infected with TB through exposure in their household. Levofloxacin is under evaluation as TPT in children exposed to M. tb strains with resistance to rifampicin and isoniazid (multidrug-resistant TB; MDR-TB).Prior to opening a phase 3 prevention trial in children <5 years exposed to MDR-TB, the pharmacokinetics and safety of a novel formulation of levofloxacin given daily was evaluated as part of a lead-in study. We conducted an exploratory qualitative study of 10 caregivers’ experiences of administering this formulation. We explored how the acceptability of levofloxacin as TPT is shaped by the broader impacts of MDR-TB on the overall psychological, social, and financial wellbeing of caregivers, many of whom also had experienced MDR-TB.Caregivers reported that the novel levofloxacin formulation was acceptable. However, caregivers described significant psychosocial challenges in the process of incorporating TPT administration to their children into their daily lives, including financial instability, withdrawal of social support and stigma. When caregivers themselves were sick, these challenges became even more acute. Although new child-friendly formulations can ameliorate some of the pragmatic challenges related to TPT preparation and administration, the overall psychosocial burden on caregivers responsible for administering TPT remains a major determinant of effective MDR-TB prevention in children.

Journal article

Kaforou M, Broderick C, Vito O, Levin M, Scriba T, Seddon Jet al., 2022, Transcriptomics for child and adolescent tuberculosis, Immunological Reviews, Vol: 309, ISSN: 0105-2896

Tuberculosis (TB) in humans is caused by Mycobacterium tuberculosis (Mtb). It is estimated that 70 million children (<15 years) are currently infected with Mtb, with 1.2 million each year progressing to disease. Of these, a quarter die. The risk of progression from Mtb infection to disease and from disease to death is dependent on multiple pathogen and host factors. Age is a central component in all these transitions. The natural history of TB in children and adolescents is different to adults, leading to unique challenges in the development of diagnostics, therapeutics, and vaccines. The quantification of RNA transcripts, encoded in the genome in specific cells or in the peripheral blood, using high-throughput methods, such as microarray analysis or RNA sequencing, are emerging technologies. RNA sequencing can shed light into the host immune response to Mtb during infection and disease, as well as understanding treatment response, disease severity and vaccination, in a global hypothesis-free manner. Additionally, gene expression profiling can be used for biomarker discovery, to diagnose disease, predict future disease progression and to monitor response to treatment. Here, we review the role of transcriptomics in children and adolescents, focussed mainly on work done in blood, to understand disease biology and to discriminate disease states to assist clinical decision-making. In recent years, studies with a specific paediatric and adolescent focus have identified blood gene expression markers with diagnostic or prognostic potential that meet or exceed the current sensitivity and specificity targets for diagnostic tools. Diagnostic and prognostic gene expression signatures identified through high-throughput methods are currently being translated into diagnostic tests.

Journal article

Dodd PJ, Mafirakureva N, Seddon JA, McQuaid CFet al., 2022, The global impact of household contact management for children on multidrug-resistant and rifampicin-resistant tuberculosis cases, deaths, and health-system costs in 2019: a modelling study, LANCET GLOBAL HEALTH, Vol: 10, Pages: E1034-E1044, ISSN: 2214-109X

Journal article

Groschel MI, van den Boom M, Dixit A, Skrahina A, Dodd PJ, Migliori GB, Seddon JA, Farhat MRet al., 2022, Management of childhood MDR-TB in Europe and Central Asia: report of a Regional WHO meeting, INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE, Vol: 26, Pages: 433-440, ISSN: 1027-3719

Journal article

Lopez-Varela E, Abulfathi AA, Strydom N, Goussard P, van Wyk AC, Demers AM, Van Deventer A, Garcia-Prats AJ, van der Merwe J, Zimmerman M, Carter CL, Janson J, Morrison J, Reuter H, Decloedt EH, Seddon JA, Svensson EM, Warren R, Savic RM, Dartois V, Hesseling ACet al., 2022, Drug concentration at the site of disease in children with pulmonary tuberculosis, Journal of Antimicrobial Chemotherapy, Vol: 77, Pages: 1710-1719, ISSN: 0305-7453

BackgroundCurrent TB treatment for children is not optimized to provide adequate drug levels in TB lesions. Dose optimization of first-line antituberculosis drugs to increase exposure at the site of disease could facilitate more optimal treatment and future treatment-shortening strategies across the disease spectrum in children with pulmonary TB.ObjectivesTo determine the concentrations of first-line antituberculosis drugs at the site of disease in children with intrathoracic TB.MethodsWe quantified drug concentrations in tissue samples from 13 children, median age 8.6 months, with complicated forms of pulmonary TB requiring bronchoscopy or transthoracic surgical lymph node decompression in a tertiary hospital in Cape Town, South Africa. Pharmacokinetic models were used to describe drug penetration characteristics and to simulate concentration profiles for bronchoalveolar lavage, homogenized lymph nodes, and cellular and necrotic lymph node lesions.ResultsIsoniazid, rifampicin and pyrazinamide showed lower penetration in most lymph node areas compared with plasma, while ethambutol accumulated in tissue. None of the drugs studied was able to reach target concentration in necrotic lesions.ConclusionsDespite similar penetration characteristics compared with adults, low plasma exposures in children led to low site of disease exposures for all drugs except for isoniazid.

Journal article

Gunasekera KS, Vonasek B, Oliwa J, Triasih R, Lancioni C, Graham SM, Seddon JA, Marais BJet al., 2022, Diagnostic Challenges in Childhood Pulmonary Tuberculosis-Optimizing the Clinical Approach, PATHOGENS, Vol: 11

Journal article

du Preez K, Jenkins H, Donald P, Solomons R, Graham S, Schaaf S, Starke J, Hesseling A, Seddon Jet al., 2022, Tuberculous meningitis in children: a forgotten public health emergency, Frontiers in Neurology, Vol: 13, Pages: 1-9, ISSN: 1664-2295

Tuberculous meningitis (TBM) remains a major cause of morbidity and mortality in children with tuberculosis (TB), yet there arecurrently no estimates of the global burden of paediatric TBM. Due to frequent non-specific clinical presentation and limited andinadequate diagnostic tests, children with TBM are often diagnosed late or die undiagnosed. Even when diagnosed and treated, 20%of children with TBM die. Of survivors, the majority have substantial neurological disability with significant negative impact onchildren and their families. Surveillance data on this devastating form of TB can help to quantify the contribution of TBM to theoverall burden, morbidity and mortality of TB in children and the epidemiology of TB more broadly.Paediatric TBM usually occurs shortly after primary infection with Mycobacterium tuberculosis and reflects ongoing TBtransmission to children. In this article we explain the public health importance of paediatric TBM, discuss the epidemiology withinthe context of overall TB control and health system functioning and the limitations of current surveillance strategies. We provide aclear rationale for the benefit of improved surveillance of paediatric TBM using a TB care cascade framework to supportmonitoring and evaluation of paediatric TB, and TB control more broadly. Considering the public health implications of a diagnosisof TBM in children, we provide recommendations to strengthen paediatric TBM surveillance and outline how improved surveillancecan help us identify opportunities for prevention, earlier diagnosis and improved care to minimize the impact of TBM on childrenglobally.

Journal article

Turkova A, Wills GH, Wobudeya E, Chabala C, Palmer M, Kinikar A, Hissar S, Choo L, Musoke P, Mulenga V, Mave V, Joseph B, LeBeau K, Thomason MJ, Mboizi RB, Kapasa M, van der Zalm MM, Raichur P, Bhavani PK, McIlleron H, Demers A-M, Aarnoutse R, Love-Koh J, Seddon JA, Welch SB, Graham SM, Hesseling AC, Gibb DM, Crook AMet al., 2022, Shorter treatment for non-severe tuberculosis in African and Indian children, New England Journal of Medicine, Vol: 386, Pages: 911-922, ISSN: 0028-4793

Background:Two thirds of children with tuberculosis have nonsevere disease, which may be treatable with a shorter regimen than the current 6-month regimen.Methods:We conducted an open-label, treatment-shortening, noninferiority trial involving children with nonsevere, symptomatic, presumably drug-susceptible, smear-negative tuberculosis in Uganda, Zambia, South Africa, and India. Children younger than 16 years of age were randomly assigned to 4 months (16 weeks) or 6 months (24 weeks) of standard first-line antituberculosis treatment with pediatric fixed-dose combinations as recommended by the World Health Organization. The primary efficacy outcome was unfavorable status (composite of treatment failure [extension, change, or restart of treatment or tuberculosis recurrence], loss to follow-up during treatment, or death) by 72 weeks, with the exclusion of participants who did not complete 4 months of treatment (modified intention-to-treat population). A noninferiority margin of 6 percentage points was used. The primary safety outcome was an adverse event of grade 3 or higher during treatment and up to 30 days after treatment.Results:From July 2016 through July 2018, a total of 1204 children underwent randomization (602 in each group). The median age of the participants was 3.5 years (range, 2 months to 15 years), 52% were male, 11% had human immunodeficiency virus infection, and 14% had bacteriologically confirmed tuberculosis. Retention by 72 weeks was 95%, and adherence to the assigned treatment was 94%. A total of 16 participants (3%) in the 4-month group had a primary-outcome event, as compared with 18 (3%) in the 6-month group (adjusted difference, −0.4 percentage points; 95% confidence interval, −2.2 to 1.5). The noninferiority of 4 months of treatment was consistent across the intention-to-treat, per-protocol, and key secondary analyses, including when the analysis was restricted to the 958 participants (80%) independently adjudicated to have tuberc

Journal article

Dodd P, Mafirakureva N, Seddon J, McQuaid Cet al., 2022, The global impact and cost-effectiveness of multidrug- and rifampicin-resistant tuberculosis household contact management in children for 2019: a modelling study, The Lancet Global Health, ISSN: 2214-109X

Journal article

Lopez-Varela E, Garcia-Prats AJ, Seddon JA, Draper HR, Winckler J, van der Laan L, Palmer M, Burger WA, Schaaf HS, Hesseling ACet al., 2022, Treatment outcomes and safety in children with rifampicin-resistant TB, INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE, Vol: 26, Pages: 133-+, ISSN: 1027-3719

Journal article

Gureva T, Turkova A, Yablokova E, Smirnova P, Sveshnikova O, Zolotaya O, Nikishova E, Heldal E, Hinderaker S, Seddon JA, Mariandyshev Aet al., 2022, Fluoroquinolone preventive therapy for children exposed to MDR-TB, INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE, Vol: 26, Pages: 171-173, ISSN: 1027-3719

Journal article

Palmer M, Gunasekera KS, van der Zalm MM, Morrison J, Schaaf HS, Goussard P, Hesseling AC, Walters E, Seddon JAet al., 2022, The Diagnostic Accuracy of Chest Radiographic Features for Pediatric Intrathoracic Tuberculosis, CLINICAL INFECTIOUS DISEASES, Vol: 75, Pages: 1014-1021, ISSN: 1058-4838

Journal article

Salih R, van Toorn R, Seddon JA, Solomons RSet al., 2022, The impact of hyponatremia on the severity of childhood tuberculous meningitis., Front Neurol, Vol: 12, Pages: 1-9, ISSN: 1664-2295

Introduction: Hyponatremia and/or hypoglycorrhachia are commonly encountered biochemical derangements during the acute stage of childhood tuberculous meningitis (TBM). Few studies have explored the correlation between these derangements and the staging of TBM disease (severity), or explored their role as biomarkers for vascular ischemic events, hydrocephalus, or seizures. Methods: We aimed to identify the prevalence and the correlation between serum hyponatremia (mild, moderate and severe) and/or hypoglycorrhachia in relation to clinical TBM features such as stage of disease, seizures and stroke in children diagnosed with definite and probable TBM, between 1985 and 2015, at Tygerberg Hospital, Cape town, South Africa. Results: The prevalence of hyponatremia was 344 out of 481 (71.5%) patients; 169 (49.1%) had mild hyponatremia, 146 (42.4%) moderate hyponatremia and 29 (8.4%) severe hyponatremia. Children with severe hyponatremia had higher frequency of stroke [odds ratio (OR) 4.36, 95% confidence interval (CI) 1.24-15.35; p = 0.01], brainstem dysfunction (OR 7.37, 95% CI 2.92-18.61; p < 0.01), cranial nerve palsies (OR 2.48, 95% CI 1.04-5.91; p = 0.04) and non-communicating hydrocephalus (OR 2.66, 95% CI 1.09-6.44; p = 0.03). Children with moderate hyponatremia and mild hyponatremia compared to those without hyponatremia similarly were more likely to exhibit signs of brainstem dysfunction (OR 1.91, 95% CI 1.11-3.28; p = 0.02) and hydrocephalus (OR 3.18, 95% CI 1.25-8.09; p = 0.01), respectively. On multivariable analysis only brainstem dysfunction was significantly associated with severe hyponatremia [adjusted odds ratio (aOR) 4.46, 95% CI 1.62-12.30; p < 0.01]. Children with hypoglycorrhachia compared to normoglycorrhachia were more likely to have had longer symptom duration prior to admission (OR 1.87, 95% CI 1.09-3.20; p = 0.02), non-communicating hydrocephalus (OR 1.64, 95% CI 0.99-2.71; p = 0.05), higher cerebrospinal white cell counts (OR 3.00, 95% CI 1.

Journal article

Ghanaiee RM, Karimi M, Hoseini-Alfatemi SM, Seddon JA, Nasehi M, Tabarsi P, Fahimzad SA, Armin S, Akbarizadeh J, Rahimarbabi E, Azimi Let al., 2022, Household contact investigation for the detection of active tuberculosis and latent tuberculosis: A comprehensive evaluation in two high-burden provinces in Iran, NEW MICROBES AND NEW INFECTIONS, Vol: 45

Journal article

Huynh J, Abo Y-N, du Preez K, Solomons R, Dooley K, Seddon Jet al., 2021, Tuberculous meningitis in children: reducing the burden of death and disability, Pathogens, Vol: 11, ISSN: 2076-0817

Tuberculous meningitis disproportionately affects young children. As the most devastating form of tuberculosis, it is associated with unacceptably high rates of mortality and morbidity even if treated. Challenging to diagnose and treat, tuberculous meningitis commonly causes long-term neurodisability in those who do survive. There remains an urgent need for strengthened surveillance, improved rapid diagnostics technology, optimised anti-tuberculosis drug therapy, investigation of new host-directed therapy, and further research on long-term functional and neurodevelopmental outcomes to allow targeted intervention. This review focuses on the neglected field of paediatric tuberculous meningitis and bridges current clinical gaps with research questions to improve outcomes from this crippling disease.

Journal article

Marais BJ, Verkuijl S, Casenghi M, Triasih R, Hesseling AC, Mandalakas AM, Marcy O, Seddon JA, Graham SM, Amanullah Fet al., 2021, Paediatric tuberculosis - new advances to close persistent gaps, INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, Vol: 113, Pages: S63-S67, ISSN: 1201-9712

Journal article

Dodd PJ, Osman M, Cresswell F, Stadelman A, Huu Lan N, Tyhy Thuong Thuong N, Muzyamba M, Glaser L, Dlamini S, Seddon Jet al., 2021, The global burden of tuberculous meningitis in adults: a modelling study, PLOS Global Public Health, Vol: 1, Pages: 1-15, ISSN: 2767-3375

Tuberculous meningitis (TBM) is the most lethal form of tuberculosis. The incidence and mortality of TBM is unknown due to diagnostic challenges and limited disaggregated reporting of treated TBM by existing surveillance systems. We aimed to estimate the incidence and mortality of TBM in adults (15+ years) globally. Using national surveillance data from Brazil, South Africa, the United Kingdom, the United States of America, and Vietnam, we estimated the fraction of reported tuberculosis that is TBM, and the case fatality ratios for treated TBM in each of these countries. We adjusted these estimates according to findings from a systematic review and meta-analysis and applied them to World Health Organization tuberculosis notifications and estimates to model the global TBM incidence and mortality. Assuming the case detection ratio (CDR) for TBM was the same as all TB, we estimated that in 2019, 164,000 (95% UI; 129,000–199,000) adults developed TBM globally; 23% were among people living with HIV. Almost 60% of incident TBM occurred in males and 20% were in adults 25–34 years old. 70% of global TBM incidence occurred in Southeast Asia and Africa. We estimated that 78,200 (95% UI; 52,300–104,000) adults died of TBM in 2019, representing 48% of incident TBM. TBM case fatality in those treated was on average 27%. Sensitivity analysis assuming improved detection of TBM compared to other forms of TB (CDR odds ratio of 2) reduced estimated global mortality to 54,900 (95% UI; 32,200–77,700); assuming instead worse detection for TBM (CDR odds ratio of 0.5) increased estimated mortality to 125,000 (95% UI; 88,800–161,000). Our results highlight the need for improved routine TBM monitoring, especially in high burden countries. Reducing TBM incidence and mortality will be necessary to achieve the End TB Strategy targets.

Journal article

Moscibrodzki P, Enane LA, Hoddinott G, Brooks MB, Byron V, Furin J, Seddon JA, Meyersohn L, Chiang SSet al., 2021, The impact of tuberculosis on the well-being of adolescents and young adults, Pathogens, Vol: 10, Pages: 1-17, ISSN: 2076-0817

The health needs of adolescents and young adults (AYAs) have been neglected in tuberculosis (TB) care, control, and research. AYAs, who are distinct from younger children and older adults, undergo dynamic physical, psychological, emotional, cognitive, and social development. Five domains of adolescent well-being are crucial to a successful transition between childhood and adulthood: (1) Good health; (2) connectedness and contribution to society; (3) safety and a supportive environment; (4) learning, competence, education, skills, and employability; and (5) agency and resilience. This review summarizes the evidence of the impact of TB disease and treatment on these five domains of AYA well-being.

Journal article

Olbrich L, Stockdale L, Basu Roy R, Song R, Cicin-Sain L, Whittaker E, Prendergast AJ, Fletcher H, Seddon JAet al., 2021, Understanding the interaction between cytomegalovirus and tuberculosis in children: The way forward, PLoS Pathogens, Vol: 17, Pages: 1-21, ISSN: 1553-7366

Over 1 million children develop tuberculosis (TB) each year, with a quarter dying. Multiple factors impact the risk of a child being exposed to Mycobacterium tuberculosis (Mtb), the risk of progressing to TB disease, and the risk of dying. However, an emerging body of evidence suggests that coinfection with cytomegalovirus (CMV), a ubiquitous herpes virus, impacts the host response to Mtb, potentially influencing the probability of disease progression, type of TB disease, performance of TB diagnostics, and disease outcome. It is also likely that infection with Mtb impacts CMV pathogenesis. Our current understanding of the burden of these 2 diseases in children, their immunological interactions, and the clinical consequence of coinfection is incomplete. It is also unclear how potential interventions might affect disease progression and outcome for TB or CMV. This article reviews the epidemiological, clinical, and immunological literature on CMV and TB in children and explores how the 2 pathogens interact, while also considering the impact of HIV on this relationship. It outlines areas of research uncertainty and makes practical suggestions as to potential studies that might address these gaps. Current research is hampered by inconsistent definitions, study designs, and laboratory practices, and more consistency and collaboration between researchers would lead to greater clarity. The ambitious targets outlined in the World Health Organization End TB Strategy will only be met through a better understanding of all aspects of child TB, including the substantial impact of coinfections.

Journal article

Purchase S, Batist E, Mmile N, Nkosi S, Workman J, Martinson N, Fairlie L, Schaaf HS, Choo L, McGowan C, Crook AM, Seddon JA, Hesseling ACet al., 2021, Challenges in recruiting children to a multidrug-resistant TB prevention trial, INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE, Vol: 25, Pages: 814-822, ISSN: 1027-3719

Journal article

van Toorn R, Zaharie S-D, Seddon JA, van der Kuip M, van Furth AM, Schoeman JF, Solomons RSet al., 2021, The use of thalidomide to treat children with tuberculosis meningitis: A review, TUBERCULOSIS, Vol: 130, ISSN: 1472-9792

Journal article

Noguera-Julian A, Buonsenso D, McKenna L, Seddon JA, Ritz Net al., 2021, Availability of fixed-dose, child-friendly formulations of first-line tuberculosis drugs in Europe, EUROPEAN RESPIRATORY JOURNAL, Vol: 58, ISSN: 0903-1936

Journal article

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: respub-action=search.html&id=00231616&limit=30&person=true