Publications
217 results found
Coussens AK, Zaidi SMA, Allwood BW, et al., 2024, Classification of early tuberculosis states to guide research for improved care and prevention: an international Delphi consensus exercise., Lancet Respir Med
The current active-latent paradigm of tuberculosis largely neglects the documented spectrum of disease. Inconsistency with regard to definitions, terminology, and diagnostic criteria for different tuberculosis states has limited the progress in research and product development that are needed to achieve tuberculosis elimination. We aimed to develop a new framework of classification for tuberculosis that accommodates key disease states but is sufficiently simple to support pragmatic research and implementation. Through an international Delphi exercise that involved 71 participants representing a wide range of disciplines, sectors, income settings, and geographies, consensus was reached on a set of conceptual states, related terminology, and research gaps. The International Consensus for Early TB (ICE-TB) framework distinguishes disease from infection by the presence of macroscopic pathology and defines two subclinical and two clinical tuberculosis states on the basis of reported symptoms or signs of tuberculosis, further differentiated by likely infectiousness. The presence of viable Mycobacterium tuberculosis and an associated host response are prerequisites for all states of infection and disease. Our framework provides a clear direction for tuberculosis research, which will, in time, improve tuberculosis clinical care and elimination policies.
Shavuka O, Lipumbu E, Boois L, et al., 2024, Enhanced active case finding of drug-resistant tuberculosis in Namibia: a protocol for the hotspots, hospitals, and households (H3TB) study, BMJ Open, Vol: 14, ISSN: 2044-6055
Introduction: Namibia is a high tuberculosis (TB)-burden country with an estimated incidence of 460/100 000 (around 12 000 cases) per year. Approximately 4.5% of new cases and 7.9% of previously treated TB cases are multidrug resistant (MDR) and 47% of patients with MDR-TB are HIV coinfected. Published data suggest a clustering of MDR-TB transmission in specific areas. Identifying transmission clusters is key to implementing high-yield and cost-effective interventions. This includes knowing the yield of finding TB cases in high-transmission zones (eg, community hotspots, hospitals or households) to deliver community-based interventions. We aim to identify such transmission zones for enhanced case finding and evaluate the effectiveness of this approach.Methods and analysis: H3TB is an observational cross-sectional study evaluating MDR-TB active case finding strategies. Sputum samples from MDR-TB cases in three regions of Namibia will be evaluated by whole genome sequencing (WGS) in addition to routine sputum investigations (Xpert MTB/RIF, culture and drug susceptibility testing). We will collect information on household contacts, use of community spaces and geographical map intersections between participants, synthesising these data to identify transmission hotspots. We will look at the feasibility, acceptability, yield and cost of case finding strategies in these hotspots, and in households of patients with MDR-TB and visitors of hospitalised patients with MDR-TB. A compartmental transmission dynamic model will be constructed to evaluate the impact and cost-effectiveness of the strategies if scaled.Ethics and dissemination: Ethics approval was obtained. Participants will give informed consent. H3TB will capitalise on a partnership with the Ministry of Health and Social Services to follow up individuals diagnosed with MDR-TB and integrate WGS data with innovative contact network mapping, to allow enhanced case finding. Study data will contribute towards a syst
van der zalm M, jongen V, swanepoel R, et al., 2024, Impaired lung function in adolescents with pulmonary tuberculosis during treatment and following treatment completion, EClinicalMedicine, Vol: 67, ISSN: 2589-5370
Background:Little is known about post-tuberculosis lung disease in adolescents. We prospectively assessed lung function in adolescents with microbiologically confirmed pulmonary tuberculosis during treatment and after treatment completion.Methods:In a prospective study, we enrolled adolescents diagnosed with microbiologically confirmed tuberculosis and healthy tuberculosis-exposed household controls, between October 2020 and July 2021 in Cape Town, South Africa. Spirometry, plethysmography, diffusion capacity lung function tests and 6-min walking test (6MWT) were completed according to international guidelines 2 months into treatment and following treatment completion. Abnormal lung function was defined as abnormal spirometry (z-score < −1.64 for forced expiratory volume in 1 s (FEV1) and/or forced vital capacity (FVC) and/or FEV1/FVC), plethysmography (total lung capacity (TLC) < 80% of predicted, residual volume over TLC of >45%) and/or diffusion capacity (DLCO z-score < −1.64).Findings:One-hundred adolescents were enrolled; 50 (50%) with tuberculosis and 50 (50%) healthy tuberculosis-exposed controls. Of the 50 adolescents with tuberculosis, ten had multidrug-resistant tuberculosis. Mean age of the group was 14.9 years (SD 2.7), 6 (6.0%) were living with HIV and 9 (9.0%) were previously treated for tuberculosis. Lung function improved over time; during treatment abnormal lung function was found in 76% of adolescents with tuberculosis, compared to 65% after treatment completion. Spirometry indices were lower in adolescents with tuberculosis compared to controls, both at 2 months and after treatment completion. Plethysmography in adolescents with tuberculosis showed that air-trapping was more common during treatment than in controls (12% vs 0%, respectively, p = 0.017); which improved following treatment completion. Adolescents with tuberculosis both during and after treatment completion walked a shorter distance than controls.Interpretation
du Cros P, Greig J, Alffenaar J-WC, et al., 2023, Standards for clinical trials for treating TB., Int J Tuberc Lung Dis, Vol: 27, Pages: 885-898
BACKGROUND: The value, speed of completion and robustness of the evidence generated by TB treatment trials could be improved by implementing standards for best practice.METHODS: A global panel of experts participated in a Delphi process, using a 7-point Likert scale to score and revise draft standards until consensus was reached.RESULTS: Eleven standards were defined: Standard 1, high quality data on TB regimens are essential to inform clinical and programmatic management; Standard 2, the research questions addressed by TB trials should be relevant to affected communities, who should be included in all trial stages; Standard 3, trials should make every effort to be as inclusive as possible; Standard 4, the most efficient trial designs should be considered to improve the evidence base as quickly and cost effectively as possible, without compromising quality; Standard 5, trial governance should be in line with accepted good clinical practice; Standard 6, trials should investigate and report strategies that promote optimal engagement in care; Standard 7, where possible, TB trials should include pharmacokinetic and pharmacodynamic components; Standard 8, outcomes should include frequency of disease recurrence and post-treatment sequelae; Standard 9, TB trials should aim to harmonise key outcomes and data structures across studies; Standard 10, TB trials should include biobanking; Standard 11, treatment trials should invest in capacity strengthening of local trial and TB programme staff.CONCLUSION: These standards should improve the efficiency and effectiveness of evidence generation, as well as the translation of research into policy and practice.
Zaidi SMA, Coussens AK, Seddon JA, et al., 2023, Beyond latent and active tuberculosis: a scoping review of conceptual frameworks., EClinicalMedicine, Vol: 66
There is growing recognition that tuberculosis (TB) infection and disease exists as a spectrum of states beyond the current binary classification of latent and active TB. Our aim was to systematically map and synthesize published conceptual frameworks for TB states. We searched MEDLINE, Embase and EMcare for review articles from 1946 to September 2023. We included 40 articles that explicitly described greater than two states for TB. We identified that terminology, definitions and diagnostic criteria for additional TB states within these articles were inconsistent. Eight broad conceptual themes were identified that were used to categorize TB states: State 0: Mycobacterium tuberculosis (Mtb) elimination with innate immune response (n = 25/40, 63%); State I: Mtb elimination by acquired immune response (n = 31/40, 78%); State II: Mtb infection not eliminated but controlled (n = 37/40, 93%); State III: Mtb infection not controlled (n = 24/40, 60%); State IV: bacteriologically positive without symptoms (n = 26/40, 65%); State V: signs or symptoms associated with TB (n = 39/40, 98%); State VI: severe or disseminated TB disease (n = 11/40, 28%); and State VII: previous history of TB (n = 5/40, 13%). Consensus on a non-binary framework that includes additional TB states is required to standardize scientific communication and to inform advancements in research, clinical and public health practice.
Achar J, Seddon JA, Knight GM, et al., 2023, Guiding pragmatic treatment choices for rifampicin-resistant tuberculosis in the absence of second-line drug susceptibility testing., Eur Respir J, Vol: 62
Swanepoel J, van Zyl G, Hesseling A, et al., 2023, Human cytomegalovirus immunoglobulin G response and pulmonary tuberculosis in adolescents: a case-control study, Open Forum Infectious Diseases, Vol: 10, ISSN: 2328-8957
BackgroundEmerging evidence suggests a link between infection with herpes viruses, particularly human cytomegalovirus (HCMV) and Epstein Barr Virus (EBV), and progression to tuberculosis (TB) disease.MethodsAn unmatched case-control study was conducted amongst adolescents aged 10-19 years enrolled in an observational study (Teen TB), between November 2020 and November 2021, in Cape Town, South Africa. Fifty individuals with pulmonary TB and 51 healthy TB-exposed individuals without TB were included. Demographics and clinical data were obtained, and serum samples collected at enrolment were tested for HCMV IgG and EBV Nuclear Antigen (EBNA) IgG using two automated enzyme immunoassays. Odds ratios (ORs) were estimated using unconditional logistic regression.ResultsThe median age of 101 participants was 15 years (interquartile range [IQR] 13 to 17); 55 (54%) were female. All participants were HCMV IgG seropositive and 95% were EBNA IgG seropositive. Individuals with TB had higher HCMV IgG titres than healthy controls (p=0.04). Individuals with upper tertile HCMV IgG titres had a 3.7 times greater odds of pulmonary TB compared to those with IgG titres in the lower tertile (95%CI: 1.05–12.84; p=0.04). There was a trend for increasing odds of pulmonary TB with increasing titres of HCMV IgG (p=0.04). In contrast, there was no association between TB and higher EBNA IgG values.ConclusionsThere is a high prevalence of sensitisation to HCMV and EBV amongst adolescents in this high-TB burden setting. Higher HCMV IgG titres were associated with pulmonary TB in adolescents.
Chabala C, Turkova A, Kapasa M, et al., 2023, Inadequate lopinavir concentrations with modified 8-hourly lopinavir/ritonavir 4:1 dosing during rifampicin-based tuberculosis treatment in children living with HIV, The Pediatric Infectious Disease Journal, Vol: 42, Pages: 899-904, ISSN: 0891-3668
BACKGROUND: Lopinavir/ritonavir plasma concentrations are profoundly reduced when co-administered with rifampicin. Super-boosting of lopinavir/ritonavir is limited by nonavailability of single-entity ritonavir, while double-dosing of co-formulated lopinavir/ritonavir given twice-daily produces suboptimal lopinavir concentrations in young children. We evaluated whether increased daily dosing with modified 8-hourly lopinavir/ritonavir 4:1 would maintain therapeutic plasma concentrations of lopinavir in children living with HIV receiving rifampicin-based antituberculosis treatment. METHODS: Children with HIV/tuberculosis coinfection weighing 3.0 to 19.9 kg, on rifampicin-based antituberculosis treatment were commenced or switched to 8-hourly liquid lopinavir/ritonavir 4:1 with increased daily dosing using weight-band dosing approach. A standard twice-daily dosing of lopinavir/ritonavir was resumed 2 weeks after completing antituberculosis treatment. Plasma sampling was conducted during and 4 weeks after completing antituberculosis treatment. RESULTS: Of 20 children enrolled; 15, 1-7 years old, had pharmacokinetics sampling available for analysis. Lopinavir concentrations (median [range]) on 8-hourly lopinavir/ritonavir co-administered with rifampicin (n = 15; area under the curve 0-24 55.32 mg/h/L [0.30-398.7 mg/h/L]; C max 3.04 mg/L [0.03-18.6 mg/L]; C 8hr 0.90 mg/L [0.01-13.7 mg/L]) were lower than on standard dosing without rifampicin (n = 12; area under the curve 24 121.63 mg/h/L [2.56-487.3 mg/h/L]; C max 9.45 mg/L [0.39-26.4 mg/L]; C 12hr 3.03 mg/L [0.01-17.7 mg/L]). During and after rifampicin cotreatment, only 7 of 15 (44.7%) and 8 of 12 (66.7%) children, respectively, achieved targeted pre-dose lopinavir concentrations ≥1mg/L. CONCLUSIONS: Modified 8-hourly dosing of lopinavir/ritonavir failed to achieve adequate lopinavir concentrations with concurrent antituberculos
Chiang SS, Graham SM, Schaaf HS, et al., 2023, Clinical standards for drug-susceptible TB in children and adolescents., International Journal of Tuberculosis and Lung Disease, Vol: 27, Pages: 584-598, ISSN: 1027-3719
BACKGROUND: These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents.METHODS: Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document.RESULTS: Eight standards were identified: Standard 1, Age and developmental stage are critical considerations in the assessment and management of TB; Standard 2, Children and adolescents with symptoms and signs of TB disease should undergo prompt evaluation, and diagnosis and treatment initiation should not depend on microbiological confirmation; Standard 3, Treatment initiation is particularly urgent in children and adolescents with presumptive TB meningitis and disseminated (miliary) TB; Standard 4, Children and adolescents should be treated with an appropriate weight-based regimen; Standard 5, Treating TB infection (TBI) is important to prevent disease; Standard 6, Children and adolescents should receive home-based/community-based treatment support whenever possible; Standard 7, Children, adolescents, and their families should be provided age-appropriate support to optimise engagement in care and clinical outcomes; and Standard 8, Case reporting and contact tracing should be conducted for each child and adolescent.CONCLUSION: These consensus-based clinical standards, which should be adapted to local contexts, will improve the care of children and adolescents affected by TB.
Patankar S, Cruz AT, Douglas-Jones B, et al., 2023, Making the Case for All-Oral, Shorter Regimens for Children with Drug-Resistant Tuberculosis, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 208, Pages: 130-131, ISSN: 1073-449X
Garcia-Prats AJ, Hoddinott G, Howell P, et al., 2023, Children deserve simple, short, safe, and effective treatment for rifampicin-resistant tuberculosis, LANCET INFECTIOUS DISEASES, Vol: 23, ISSN: 1473-3099
Swanepoel J, van der Zalm MM, Preiser W, et al., 2023, SARS-CoV-2 infection and pulmonary tuberculosis in children and adolescents: a case-control study, BMC Infectious Diseases, Vol: 23, Pages: 1-10, ISSN: 1471-2334
BackgroundThe Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) pandemic has had an impact on the global tuberculosis (TB) epidemic but evidence on the possible interaction between SARS-CoV-2 and TB, especially in children and adolescents, remains limited. We aimed to evaluate the relationship between previous infection with SARS-CoV-2 and the risk of TB in children and adolescents.MethodsAn unmatched case-control study was conducted using SARS-CoV-2 unvaccinated children and adolescents recruited into two observational TB studies (Teen TB and Umoya), between November 2020 and November 2021, in Cape Town, South Africa. Sixty-four individuals with pulmonary TB (aged < 20 years) and 99 individuals without pulmonary TB (aged < 20 years) were included. Demographics and clinical data were obtained. Serum samples collected at enrolment underwent quantitative SARS-CoV-2 anti-spike immunoglobulin G (IgG) testing using the Abbott SARS-CoV-2 IgG II Quant assay. Odds ratios (ORs) for TB were estimated using unconditional logistic regression.ResultsThere was no statistically significant difference in the odds of having pulmonary TB between those who were SARS-CoV-2 IgG seropositive and those who were seronegative (adjusted OR 0.51; 95% CI: 0.23–1.11; n = 163; p = 0.09). Of those with positive SARS-CoV-2 serology indicating prior infection, baseline IgG titres were higher in individuals with TB compared to those without TB (p = 0.04) and individuals with IgG titres in the highest tertile were more likely to have pulmonary TB compared to those with IgG levels in the lowest tertile (OR: 4.00; 95%CI: 1.13– 14.21; p = 0.03).ConclusionsOur study did not find convincing evidence that SARS-CoV-2 seropositivity was associated with subsequent pulmonary TB disease; however, the association between magnitude of SARS-CoV-2 IgG response and pulmonary TB warrants further investigat
Palmer M, Seddon JA, van der Zalm MM, et al., 2023, Optimising computer aided detection to identify intra-thoracic tuberculosis on chest x-ray in South African children, PLOS Global Public Health, Vol: 3, Pages: 1-15, ISSN: 2767-3375
Diagnostic tools for paediatric tuberculosis remain limited, with heavy reliance on clinical algorithms which include chest x-ray. Computer aided detection (CAD) for tuberculosis on chest x-ray has shown promise in adults. We aimed to measure and optimise the performance of an adult CAD system, CAD4TB, to identify tuberculosis on chest x-rays from children with presumptive tuberculosis. Chest x-rays from 620 children <13 years enrolled in a prospective observational diagnostic study in South Africa, were evaluated. All chest x-rays were read by a panel of expert readers who attributed each with a radiological reference of either 'tuberculosis' or 'not tuberculosis'. Of the 525 chest x-rays included in this analysis, 80 (40 with a reference of 'tuberculosis' and 40 with 'not tuberculosis') were allocated to an independent test set. The remainder made up the training set. The performance of CAD4TB to identify 'tuberculosis' versus 'not tuberculosis' on chest x-ray against the radiological reference read was calculated. The CAD4TB software was then fine-tuned using the paediatric training set. We compared the performance of the fine-tuned model to the original model. Our findings were that the area under the receiver operating characteristic curve (AUC) of the original CAD4TB model, prior to fine-tuning, was 0.58. After fine-tuning there was an improvement in the AUC to 0.72 (p = 0.0016). In this first-ever description of the use of CAD to identify tuberculosis on chest x-ray in children, we demonstrate a significant improvement in the performance of CAD4TB after fine-tuning with a set of well-characterised paediatric chest x-rays. CAD has the potential to be a useful additional diagnostic tool for paediatric tuberculosis. We recommend replicating the methods we describe using a larger chest x-ray dataset from a more diverse population and evaluating the potential role of CAD to replace a human-read chest x-ray within treatment-decision algorithms for paediatric tub
Gunasekera K, Seddon J, 2023, Development and validation of treatment-decision algorithms for children evaluated for pulmonary tuberculosis: an individual participant data meta-analysis, The Lancet Child & Adolescent Health, Vol: 7, Pages: 336-346, ISSN: 2352-4642
BackgroundMany children with pulmonary tuberculosis remain undiagnosed and untreated with related high morbidity and mortality. Recent advances in childhood tuberculosis algorithm development have incorporated prediction modelling, but studies so far have been small and localised, with limited generalisability. We aimed to evaluate the performance of currently used diagnostic algorithms and to use prediction modelling to develop evidence-based algorithms to assist in tuberculosis treatment decision making for children presenting to primary health-care centres.MethodsFor this meta-analysis, we identified individual participant data from a WHO public call for data on the management of tuberculosis in children and adolescents and referral from childhood tuberculosis experts. We included studies that prospectively recruited consecutive participants younger than 10 years attending health-care centres in countries with a high tuberculosis incidence for clinical evaluation of pulmonary tuberculosis. We collated individual participant data including clinical, bacteriological, and radiological information and a standardised reference classification of pulmonary tuberculosis. Using this dataset, we first retrospectively evaluated the performance of several existing treatment-decision algorithms. We then used the data to develop two multivariable prediction models that included features used in clinical evaluation of pulmonary tuberculosis—one with chest x-ray features and one without—and we investigated each model's generalisability using internal–external cross-validation. The parameter coefficient estimates of the two models were scaled into two scoring systems to classify tuberculosis with a prespecified sensitivity target. The two scoring systems were used to develop two pragmatic, treatment-decision algorithms for use in primary health-care settings.FindingsOf 4718 children from 13 studies from 12 countries, 1811 (38·4%) were classified as having
Buonsenso D, Seddon JA, Esposito S, et al., 2023, QuantiFERON-TB Gold Plus Performance in Children: A Narrative Review, PEDIATRIC INFECTIOUS DISEASE JOURNAL, Vol: 42, Pages: E158-E165, ISSN: 0891-3668
Nightingale R, Carlin F, Meghji J, et al., 2023, Post-TB health and wellbeing, INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE, Vol: 27, Pages: 248-+, ISSN: 1027-3719
- Author Web Link
- Cite
- Citations: 4
Channon-Wells S, Vito O, McArdle AJ, et al., 2023, Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study, The Lancet Rheumatology, Vol: 5, Pages: e184-e199, ISSN: 2665-9913
BackgroundMultisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments.MethodsThe Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370.FindingsWe enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologica
Cruz ATT, Seddon JAA, 2023, Vulnerable Children With Presumptive Tuberculosis: When Will This Population Be Prioritized?, PEDIATRICS, Vol: 151, ISSN: 0031-4005
Saal C-L, Springer P, Seddon JA, et al., 2023, Risk factors of poor developmental outcome in children with tuberculous meningitis, CHILDS NERVOUS SYSTEM, Vol: 39, Pages: 1029-1039, ISSN: 0256-7040
Chiang SS, Waterous PM, Atieno VF, et al., 2023, Caring for Adolescents and Young Adults With Tuberculosis or at Risk of Tuberculosis: Consensus Statement From an International Expert Panel, JOURNAL OF ADOLESCENT HEALTH, Vol: 72, Pages: 323-331, ISSN: 1054-139X
- Author Web Link
- Cite
- Citations: 1
Marcy O, Wobudeya E, Font H, et al., 2023, 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 INFECTIOUS DISEASES, Vol: 23, Pages: 341-351, ISSN: 1473-3099
- Author Web Link
- Cite
- Citations: 2
Nicholson T, Seddon J, Osman M, 2023, A systematic review of risk factors for mortality among tuberculosis patients in South Africa, Systematic Reviews, Vol: 12, Pages: 1-16, ISSN: 2046-4053
BackgroundTuberculosis (TB)-associated mortality in South Africa remains high. This review aimed to systematically assess risk factors associated with death during TB treatment in South African patients.MethodsWe conducted a systematic review of TB research articles published between 2010 and 2018. We searched BioMed Central (BMC), PubMed®, EBSCOhost, Cochrane, and SCOPUS for publications between January 2010 and December 2018. Searches were conducted between August 2019 and October 2019. We included randomised control trials (RCTs), case control, cross sectional, retrospective, and prospective cohort studies where TB mortality was a primary endpoint and effect measure estimates were provided for risk factors for TB mortality during TB treatment. Due to heterogeneity in effect measures and risk factors evaluated, a formal meta-analysis of risk factors for TB mortality was not appropriate. A random effects meta-analysis was used to estimate case fatality ratios (CFRs) for all studies and for specific subgroups so that these could be compared. Quality assessments were performed using the Newcastle-Ottawa scale or the Cochrane Risk of Bias Tool.ResultsWe identified 1995 titles for screening, 24 publications met our inclusion criteria (one cross-sectional study, 2 RCTs, and 21 cohort studies). Twenty-two studies reported on adults (n = 12561) and two were restricted to children < 15 years of age (n = 696). The CFR estimated for all studies was 26.4% (CI 18.1–34.7, n = 13257 ); 37.5% (CI 24.8-50.3, n = 5149) for drug-resistant (DR) TB; 12.5% (CI 1.1–23.9, n = 1935) for drug-susceptible (DS) TB; 15.6% (CI 8.1–23.2, n = 6173) for studies in which drug susceptibility was mixed or not specified; 21.3% (CI 15.3-27.3, n = 7375) for people living with HIV/AIDS (PLHIV); 19.2% (CI 7.7–30.7, n = 1691) in HIV-negative TB patients; and 6.8% (CI 4.9–8.7, n = 696) in paediatric studies. The main risk factors associated with TB mortality were HIV in
Cardoso Pinto A, Shariq S, Ranasinghe L, et al., 2023, Reasons for reductions in routine childhood immunisation uptake during the COVID-19 pandemic in low- and middle-income countries: a systematic review, PLOS Global Public Health, Vol: 3, Pages: 1-17, ISSN: 2767-3375
The coronavirus disease 2019 (COVID-19) pandemic has resulted in a substantial decline in routine immunisation coverage in children globally, especially in low- and middle-income countries (LMICs). This study summarises the reasons for disruptions to routine child immunisations in LMICs. A systematic review (PROSPERO CRD42021286386) was conducted following PRISMA 2020 guidelines. Six databases were searched: MEDLINE, Embase, Global Health, CINAHL, Scopus and MedRxiv, on 11/02/2022. Observational and qualitative studies published from January 2020 onwards were included if exploring reasons for missed immunisations during the COVID-19 pandemic in LMICs. Study appraisal used National Heart, Lung, and Blood Institute and Critical Appraisal Skills Programme tools. Reasons for disruption were defined with descriptive codes; cross-sectional (quantitative) data were summarised as mean percentages of responses weighted by study population, and qualitative data were summarised narratively. A total of thirteen studies were included describing reasons behind disruptions; 7 cross-sectional (quantitative), 5 qualitative and 1 mixed methods. Seventeen reasons for disruptions were identified. In quantitative studies (total respondents = 2,853), the most common reasons identified were fear of COVID-19 and consequential avoidance of health centres (41.2%, SD ±13.3%), followed by transport challenges preventing both families and healthcare professionals from reaching vaccination services (11.1% SD ±16.6%). Most reasons stemmed from reduced healthcare-seeking (83.4%), as opposed to healthcare-delivery issues (15.2%). Qualitative studies showed a more even balance of healthcare-seeking (49.5%) and healthcare-delivery issues (50.5%), with fear of COVID-19 remaining a major identified issue (total respondents = 92). The most common reasons for disruption were parental fear of COVID-19 and avoidance of health services. Health systems must therefore prioritise public health me
López-Varela E, Munyangaju I, Chabala C, et al., 2023, Tuberculosis in children and adolescents: A forgotten group in a forgotten disease, ERS Monograph, Vol: 2023, Pages: 210-234, ISSN: 2312-508X
Despite being both treatable and preventable, TB in children and adolescents continues to cause substantial mortality and morbidity in high-incidence settings. Major challenges include missed opportunities for TB prevention and poor case detection, particularly in young children. Although historically neglected, recent developments, including the 2022 WHO child and adolescent TB guidelines, represent important milestones in improving TB prevention and care in this population. The guidelines include the use of treatment decision algorithms, shorter treatment regimens, and TPT for both drug-susceptible and DR-TB, as well as steps to address the unique needs of adolescents. Closing persistent policy-practice gaps will be necessary to ensure that these new developments are implemented effectively. This chapter emphasises the need for continued efforts to prevent and control TB in children and adolescents, which will require a multifaceted approach involving governments, health systems and communities.
Waderman DT, Palmer M, Purchase S, et al., 2022, Toward a conceptual framework of the acceptability of tuberculosis treatment in children using a theory generative approach, PLOS Global Public Health, Vol: 2, ISSN: 2767-3375
To describe an early-stage holistic framework towards evaluating factors that impact the overall acceptability of TB treatment along the TB care cascade in children. We developed a conceptual framework utilising a theory generative approach. Domains were developed through review of existing definitions and analysis of existing qualitative data undertaken in acceptability studies of TB treatment in children. Clarity of domain definitions was achieved through iterative refinement among the research team. Three domains, each comprising several dimensions, were identified to holistically evaluate treatment acceptability: (1) usability, which involves the alignment between the requirements of treatment use and caregivers’ and children’s ability to integrate TB treatment into their everyday routines, (2) receptivity, which describes the end-user’s perception and expectations of treatment and its actual use, and (3) integration, which describes the relationship between available health services and caregivers/children’s capacity to make use of those services. Our framework addresses the gaps in current research which do not account for the influence of caregivers’ and children’s contexts on TB treatment uptake and overall acceptability. This approach may support the development of more standard, holistic measures to improve TB treatment delivery and experiences and future research in children.
Swanepoel J, Zimri K, van der Zalm MM, et al., 2022, Understanding the biology, morbidity and social contexts of adolescent tuberculosis: a prospective observational cohort study protocol (Teen TB), BMJ Open, Vol: 12, ISSN: 2044-6055
Introduction: A considerable burden of the tuberculosis (TB) epidemic is found in adolescents. The reasons for increased susceptibility to TB infection and higher incidence of TB disease in adolescence, compared with the 5–10 years old age group, are incompletely understood. Despite the pressing clinical and public health need to better understand and address adolescent TB, research in this field remains limited.Methods and analysis: Teen TB is an ongoing prospective observational cohort study that aims to better understand the biology, morbidity and social context of adolescent TB. The study plans to recruit 50 adolescents (10–19 years old) with newly diagnosed microbiologically confirmed pulmonary TB disease and 50 TB-exposed controls without evidence of TB disease in Cape Town, South Africa, which is highly endemic for TB. At baseline, cases and controls will undergo a detailed clinical evaluation, chest imaging, respiratory function assessments and blood collection for viral coinfections, inflammatory cytokines and pubertal hormone testing. At 2 weeks, 2 months and 12 months, TB disease cases will undergo further chest imaging and additional lung function testing to explore the patterns of respiratory abnormalities. At week 2, cases will complete a multicomponent quantitative questionnaire about psychological and social impacts on their experiences and longitudinal, in-depth qualitative data will be collected from a nested subsample of 20 cases and their families.Ethics and dissemination: The study protocol has received ethical approval from the Stellenbosch University Health Research Ethics Committee (N19/10/148). The study findings will be disseminated through peer-reviewed publications, academic conferences and formal presentations to health professionals. Results will also be made available to participants and caregivers.
van wyk S, Nliwasa M, Seddon J, et al., 2022, Drug-resistant tuberculosis case-finding strategies: a scoping review protocol, JMIR Research Protocols, Vol: 11, Pages: 1-7, ISSN: 1929-0748
Background:Transmission of drug-resistant tuberculosis (DR-TB) is ongoing. Finding individuals with DR-TB and initiating treatment as early as possible is important to improve patient clinical outcomes and to break the chain of transmission to control the pandemic. To our knowledge systematic reviews assessing effectiveness, cost-effectiveness, acceptability, and feasibility of different case-finding strategies for DR-TB to inform research, policy, and practice have not been conducted, and it is unknown whether enough research exists to conduct such reviews. It is unknown whether case-finding strategies are similar for DR-TB and drug-susceptible TB and whether we can draw on findings from drug-susceptible reviews to inform decisions on case-finding strategies for DR-TB.Objective:This protocol aims to describe the available literature on case-finding for DR-TB and to describe case-finding strategies.Methods:We will screen systematic reviews, trials, qualitative studies, diagnostic test accuracy studies, and other primary research that specifically sought to improve DR-TB case detection. We will exclude studies that invited individuals seeking care for TB symptoms, those including individuals already diagnosed with TB, or laboratory-based studies. We will search the academic databases including MEDLINE, Embase, The Cochrane Library, Africa-Wide Information, CINAHL, Epistemonikos, and PROSPERO with no language or date restrictions. We will screen titles, abstracts, and full-text articles in duplicate. Data extraction and analyses will be performed using Excel (Microsoft Corp).Results:We will provide a narrative report with supporting figures or tables to summarize the data. A systems-based logic model, developed from a synthesis of case-finding strategies for drug-susceptible TB, will be used as a framework to describe different strategies, resulting pathways, and enhancements of pathways. The search will be conducted at the end of 2021. Title and abstract screening, f
Meier S, Seddon JA, Maasdorp E, et al., 2022, Neutrophil degranulation, NETosis and platelet degranulation pathway genes are co-induced in whole blood up to six months before tuberculosis diagnosis, PLoS One, Vol: 17, ISSN: 1932-6203
Mycobacterium tuberculosis (M.tb) causes tuberculosis (TB) and remains one of the leading causes of mortality due to an infectious pathogen. Host immune responses have been implicated in driving the progression from infection to severe lung disease. We analyzed longitudinal RNA sequencing (RNAseq) data from the whole blood of 74 TB progressors whose samples were grouped into four six-month intervals preceding diagnosis (the GC6-74 study). We additionally analyzed RNAseq data from an independent cohort of 90 TB patients with positron emission tomography-computed tomography (PET-CT) scan results which were used to categorize them into groups with high and low levels of lung damage (the Catalysis TB Biomarker study). These groups were compared to non-TB controls to obtain a complete whole blood transcriptional profile for individuals spanning from early stages of M.tb infection to TB diagnosis. The results revealed a steady increase in the number of genes that were differentially expressed in progressors at time points closer to diagnosis with 278 genes at 13-18 months, 742 at 7-12 months and 5,131 detected 1-6 months before diagnosis and 9,205 detected in TB patients. A total of 2,144 differentially expressed genes were detected when comparing TB patients with high and low levels of lung damage. There was a large overlap in the genes upregulated in progressors 1-6 months before diagnosis (86%) with those in TB patients. A comprehensive pathway analysis revealed a potent activation of neutrophil and platelet mediated defenses including neutrophil and platelet degranulation, and NET formation at both time points. These pathways were also enriched in TB patients with high levels of lung damage compared to those with low. These findings suggest that neutrophils and platelets play a critical role in TB pathogenesis, and provide details of the timing of specific effector mechanisms that may contribute to TB lung pathology.
Ranasinghe L, Achar J, Groschel M, et al., 2022, The global impact of COVID-19 on childhood tuberculosis: analysis of notification data, The Lancet Global Health, Vol: 10, Pages: e1774-e1781, 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
Garcia-Prats AJ, Starke JR, Waning B, et 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
- Author Web Link
- Cite
- Citations: 4
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.