Call | Senior Fellowship Plus (SFP) |
Programme | EDCTP2 |
Start Date | 2021-01-01 |
End Date | 2025-12-31 |
Project Code | TMA2019SFP2836 |
Status | Active |
The long-term consequences of pulmonary tuberculosis and respiratory viruses on lung health in young South African children
The overarching goal of the TB-lung FACT2 project is to improve our current understanding of the long-term impact of PTB and other LRTIs on lung health in children living in resource-limited settings.
Institution | Country |
---|---|
Stellenbosch University | South Africa |
Prospective observational cohort study
Mozambique, Manhica |
Type | Name | Title | University | Start Date | End Date |
---|---|---|---|---|---|
PhD | Michaile Anthony | Stellenbosch University, South Africa | 2021 | ||
MSc | Ingrid Courtney | Stellenbosch University, South Africa | 2021 | ||
MSc | Ruan Swanenpoel | Central University of Technology, South Africa | 2022 | ||
MPhil | Nelson Daniel | Dr | University of Cambridge | 2022 | 2023 |
Call | Career Development Fellowship (CDF) |
Programme | EDCTP2 |
Start Date | 2017-07-01 |
End Date | 2020-12-31 |
Project Code | TMA2015CDF1012 |
Status | Completed |
The impact of pulmonary tuberculosis and other lower respiratory tract pathogens on lung function in young South African children
To investigate the effect of TB, TB/ HIV co-infection and other common respiratory pathogens on lung function in young children.
Institution | Country |
---|---|
Stellenbosch University (SU) | South Africa |
Prospective observational cohort study of children with suspected pulmonary TB including healthy controls
Desmond Tutu TB Center Stellenbosch University, South Africa |
Title | University | Start Date | End Date |
---|---|---|---|
the role of respiratory viruses in respiratory illnesses early in life | University of Utrecht, the Netherlands | 2005-08-01 | 2010-12-05 |
Type | Name | Title | University | Start Date | End Date |
---|---|---|---|---|---|
MSc | Bianca Hamman | University of Stellenbosch | 2017 | 2020 | |
BSc | Ruan Swanenpoel | Central University of Technology | 2018 | 2019 | |
PhD | Michaile Anthony | University of Stellenbosch | 01-01-2021 | 31-12-2024 | |
MSc | Ingrid Courtney | University of Stellenbosch | 01-07-2020 | 31-12-2021 |
In progress- data expected to come out July 2020
doi: 10.1016/S1473-3099(19)30564-X. |
doi: 10.5588/ijtld.19.0115. |
doi: 10.1097/INF.0000000000002240. |
doi: 10.1128/JCM.00781-18. |
doi: 10.1128/JCM.00056-18. |
doi: 10.1186/s13063-018-2608-5. |
doi: 10.1093/cid/cix834. |
DOI: 10.1093/cid/ciab018 |
DOI: 10.1186/s12879-020-05653-9 |
in press |
DOI: 10.1093/cid/ciaa1666 |
DOI: 10.1159/000512531 |
DOI: 10.1080/17476348.2021.1828069 |
doi: 10.1097/INF.0000000000002900 |
doi:10.1002/ppul.25015 |
DOI: 10.1136/bmjgh-2020-002844 |
DOI: 10.5588/ijtld.20.0067 |
doi: 10.2196/19154. |
DOI: 10.1093/cid/ciab142 |
Stellenbosch University, Desmond Tutu TB Centre
Paediatrician and Clinical researcher
2018 | South African MRC Researcher Initiated grant |
2019 | Subcontract of NIH award for Influenza study |
2020 | NIH R01: Multiplexed Antigen-Specific Antibody Fc Profiling on a Chip for Point-of-Care Diagnosis of TB in HIV-infected Children |
2020 | NIH K43 Emerging Global leader award |
2020 | Stellenbosch University SEED funding for COVID-kids South Africa |
2021 | NIH R21/ R33: Development and implementation of pediatric mobile phone reflectance pulse oximeters and a hypoxemia surveillance system in South Africa |
2021 | Horizon Europe- co-investigator on VERDI- project |
2022 | South African MRC Researcher Initiated grant: The long-term consequences of SARS-CoV-2 on lung health in young South African children |
2021 | Subcontract of NIH award for Influenza/ SARS-CoV-2 study |
2021 | Administrative supplement NIH-K43 for SARS-CoV-2 work |
Type | Name | Title | University | Start Date | End Date |
---|---|---|---|---|---|
Masters | Bianca Hamman | Stellenbosch University | 2017 | 2020 | |
Bachelor Technology | Ruan Swanenpoel | Central University of Technology | 2018 | 2019 | |
Masters | Ingrid Courtney | Stellenbosch University | 2020 | 2022 | |
PhD | Michaile Anthony | Stellenbosch University | 2020 | 2024 | |
PhD | Deephti Abraham | Dr | Stellenbosch University | 2022 | 2025 |
MPhil | Nelson Daniel | Dr | University of Cambridge | 2022 | 2023 |
MPhil | RC Krause | Dr | Stellenbosch University | 2022 | 2023 |
Role | Committee/board | Start Date | End Date |
---|---|---|---|
Paediatric advisor | National TB think tank, South Africa | 2019 | |
Member | Post TB working group, Union | 2019 | |
Member | Child and adolescent TB working group, WHO | 2018 | |
Associate editor | BMC pulmonology | 2019 |
Institution | Degree | Year |
---|---|---|
University of Utrecht, Netherlands | MD | 2005-08-01 |
University Of Utrecht, Netherlands | MSc epidemiology | 2009-10-01 |
University Of Utrecht, Netherlands | PhD | 2009-12-05 |
Tuberculosis (TB) Lower Respiratory Tract Infections (LRTIs)
Background People who survive tuberculosis face clinical and societal consequences after recovery, including increased risks of recurrent tuberculosis, premature death, reduced lung function, and ongoing stigma. To describe the size of this issue, we aimed to estimate the number of individuals who developed first-episode tuberculosis between 1980 and 2019, the number who survived to 2020, and the number who have been treated within the past 5 years or 2 years.
Methods In this modelling study, we estimated the number of people who survived treated tuberculosis using country-level WHO data on tuberculosis case notifications, excluding those who died during treatment. We estimated the number of individuals surviving untreated tuberculosis using the difference between WHO country-level incidence estimates and notifications, applying published age-stratified and HIV-stratified case fatality ratios. To estimate survival with time, post-tuberculosis life tables were developed for each country-year by use of UN World Population Prospects 2019 mortality rates and published post-tuberculosis mortality hazard ratios.
Findings Between 1980 and 2019, we estimate that 363 million people (95% uncertainty interval [UI] 287 million–438 million) developed tuberculosis, of whom 172 million (169 million–174 million) were treated. Individuals who developed tuberculosis between 1980 and 2019 had lived 3480 million life-years (95% UI 3040 million–3920 million) after tuberculosis by 2020, with survivors younger than 15 years at the time of tuberculosis development contributing 12% (95% UI 7–17) of these life-years. We estimate that 155 million tuberculosis survivors (95% UI 138 million–171 million) were alive in 2020, the largest proportion (47% [37–57]) of whom were in the WHO South-East Asia region. Of the tuberculosis survivors who were alive in 2020, we estimate that 18% (95% UI 16–20) were treated in the past 5 years and 8% (7–9) were treated in the past 2 years.
Interpretation The number of tuberculosis survivors alive in 2020 is more than ten times the estimated annual tuberculosis incidence. Interventions to alleviate respiratory morbidity, screen for and prevent recurrent tuberculosis, and reduce stigma should be immediately prioritised for recently treated tuberculosis survivors.
There is a lack of holistic health-related quality of life (HRQoL) measures for young children with respiratory disease, especially in low- and middle-income countries (LMICs). We aimed to understand caregivers’ perceptions of the relevance of common HRQoL domains for children with respiratory diseases, including TB.
This study was nested in a prospective observational cohort of children presenting with respiratory symptoms presumptive of pulmonary TB. We conducted 10 semi-structured interviews to explore caregivers’ perceptions of the five commonly measured HRQoL domains: physical health, social support, emotional and psychological wellbeing, and schooling. We used case descriptive analysis and thematic coding.
Caregivers considered all five domains to be relevant. The socio-economic context framed their responses, with QoL requiring sufficient basic resources for children. HRQoL experiences varied according to the severity of the child’s symptoms, but not between TB and non-TB illnesses. Manifestations in the psychological domain were difficult to distinguish from the emotional domain. Social support included broad support for family members, indirectly benefiting the children. Caregivers were concerned about their children’s early developmental milestones and future schooling.
This exploratory study shows that HRQoL domains are relevant but require adaptation to be applicable for young children affected by respiratory illnesses living in LMICs.
Introduction: The chest radiograph (CR) remains a key tool in the diagnosis of pediatric tuberculosis (TB). In children with presumptive intrathoracic TB, we aimed to identify CR features that had high specificity for, and were strongly associated with, bacteriologically confirmed TB.
Methods: We analyzed CR data from children with presumptive intrathoracic TB prospectively enrolled in a cohort study in a high-TB burden setting and who were classified using standard clinical case definitions as "confirmed," "unconfirmed," or "unlikely" TB. We report the CR features and inter-reader agreement between expert readers who interpreted the CRs. We calculated the sensitivity and specificity of the CR features with at least moderate inter-reader agreement and analyzed the relationship between these CR features and the classification of TB in a multivariable regression model.
Results: Of features with at least moderate inter-reader agreement, enlargement of perihilar and/or paratracheal lymph nodes, bronchial deviation/compression, cavities, expansile pneumonia, and pleural effusion had a specificity of > 90% for confirmed TB, compared with unlikely TB. Enlargement of perihilar (adjusted odds ratio [aOR]: 6.6; 95% confidence interval [CI], 3.80-11.72) and/or paratracheal lymph nodes (aOR: 5.14; 95% CI, 2.25-12.58), bronchial deviation/compression (aOR: 6.22; 95% CI, 2.70-15.69), pleural effusion (aOR: 2.27; 95% CI, 1.04-4.78), and cavities (aOR: 7.45; 95% CI, 3.38-17.45) were associated with confirmed TB in the multivariate regression model, whereas alveolar opacification (aOR: 1.16; 95% CI, .76-1.77) and expansile pneumonia (aOR: 4.16; 95% CI, .93-22.34) were not.
Conclusions: In children investigated for intrathoracic TB enlargement of perihilar or paratracheal lymph nodes, bronchial compression/deviation, pleural effusion, or cavities on CR strongly support the diagnosis.
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.
The effects of SARS-CoV-2 variants on disease phenotype and severity of multisystem inflammatory syndrome in children (MIS-C) are unknown. We compared the clinical phenotype of MIS-C in 129 South African children across four distinct (Ancestral type, Beta, Delta, and Omicron) variant-driven waves and found that MIS-C remains a severe disease with a stable clinical presentation, regardless of variant.
Background: Identification of SARS-CoV-2 infected individuals is imperative to prevent hospital transmission, but symptom-based screening may fail to identify asymptomatic/mildly symptomatic infectious children and their caregivers.
Methods: A COVID-19 period prevalence study was conducted between 13 and 26 August 2020 at Tygerberg Hospital, testing all children and their accompanying asymptomatic caregivers after initial symptom screening. One nasopharyngeal swab was submitted for SARS-CoV-2 using real-time reverse-transcription polymerase chain reaction (rRT-PCR). An additional Respiratory Viral 16-multiplex rRT-PCR test was simultaneously done in children presenting with symptoms compatible with possible SARS-CoV-2 infection.
Results: SARS-Co-V 2 RT-PCR tests from 196 children and 116 caregivers were included in the analysis. The SARS-CoV-2 period prevalence in children was 5.6% (11/196) versus 15.5% (18/116) in asymptomatic caregivers (p<0.01). Presenting symptoms did not correlate with SARS-CoV-2 test positivity; children without typical symptoms of SARS-CoV-2 were more likely to be positive than those with typical symptoms (10.2% [10/99] vs 1% [1/97]; p<0.01). Children with typical symptoms (97/196; 49.5%) mainly presented with acute respiratory (68/97; 70.1%), fever (17/97; 17.5%), or gastro-intestinal complaints (12/97; 12.4%); Human Rhinovirus (23/81; 28.4%) and Respiratory Syncytial Virus (18/81; 22.2%) were frequently identified in this group. Children-caregiver pairs' SARS-CoV-2 tests were discordant in 83.3%; 15/18 infected caregivers' children tested negative. Symptom-based COVID-19 screening alone would have missed 90% of the positive children and 100% of asymptomatic but positive caregivers.
Conclusion: Given the poor correlation between SARS-CoV-2 symptoms and RT-PCR test positivity, universal testing of children and their accompanying caregivers should be considered for emergency and inpatient paediatric admissions during high COVID-19 community transmission periods. Universal PPE and optimising ventilation is likely the most effective way to control transmission of respiratory viral infections, including SARS-CoV-2, where universal testing is not feasible. In these settings, repeated point prevalence studies may be useful to inform local testing and cohorting strategies.