EDCTP Alumni Network

Fostering excellence and collaboration in the next generation of researchers

Call Senior Fellowship Plus (SFP)
Programme EDCTP2
Start Date 2021-01-01
End Date 2025-12-31
Project Code TMA2019SFP2836
Status Active

Title

The long-term consequences of pulmonary tuberculosis and respiratory viruses on lung health in young South African children

Host Organisation

Institution Country
Stellenbosch University South Africa
Call Career Development Fellowship (CDF)
Programme EDCTP2
Start Date 2017-07-01
End Date 2020-12-31
Project Code TMA2015CDF1012
Status Active

Title

The impact of pulmonary tuberculosis and other lower respiratory tract pathogens on lung function in young South African children

Objectives

To investigate the effect of TB, TB/ HIV co-infection and other common respiratory pathogens on lung function in young children.

Host Organisation

Institution Country
Stellenbosch University (SU) South Africa

Study Design

Prospective observational cohort study of children with suspected pulmonary TB including healthy controls

Sites

Desmond Tutu TB Center Stellenbosch University, South Africa

Phd Study

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

Students Supervised

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

Results & Outcomes

In progress- data expected to come out July 2020

Publications

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

Current Organisation

Stellenbosch University, Desmond Tutu TB Centre

Current Job Title

Clinical researcher

Awards

2018 South African MRC Researcher Initiated grant
2019 Subcontract of NIH award for Influenza study
2020 NIH R01
2020 NIH K43
2020 Stellenbosch University SEED funding

Students Supervised

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 2021
PhD Michaile Anthony Stellenbosch University 2020 2024

Memberships

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

Education

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

Areas Of Specialisation

Tuberculosis (TB) Lower Respiratory Tract Infections (LRTIs)

Grants

Grant Code:
OPP1212276
Source of funding:
Bill and Melinda Gates Foundation
Amount:
199948
Role:
Researcher
Start Date:
2019-01-01
End Date:
2020-01-01
Grant Code:
Subcontract to NIH (through University of the Western Cape)
Source of funding:
NIH
Amount:
100000
Role:
Principal Investigator
Start Date:
2019-01-01
End Date:
2021-01-01
Grant Code:
552767
Source of funding:
South African Medical Research Council
Amount:
38500
Role:
Principal Investigator
Start Date:
2018-01-01
End Date:
2021-01-01
Grant Code:
K43TW011028
Source of funding:
NIH
Amount:
550000
Role:
Principal Investigator
Start Date:
2020-01-01
End Date:
2025-01-01
Grant Code:
None- Stellenbosch University SEED funding
Source of funding:
Stellenbosch University
Amount:
6000
Role:
Principal Investigator
Start Date:
2020-01-01
End Date:
2021-01-01
Grant Code:
1R01AI152158-01
Source of funding:
NIH
Amount:
1400000
Role:
Principal Investigator
Start Date:
2020-01-01
End Date:
2025-01-01

Publications

Authors:
Van Der Zalm, M.M.
Van Soelen, N.
Mandalakas, A.M.
Jacobsen, M.
Detjen, A.K.
Marx, F.M.
Grewal, H.M.S.
Cotton, M.F.
Walzl, G.
Hesseling, A.C.
Date:
2016-01-01
Journal:
Pediatric Infectious Disease Journal
Content:
Authors:
James A Seddon
Date:
2021-02-25
Journal:
Lancet Infectious Diseases
Content:

 

 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.

Identifiers:
Authors:
Walters, E.
Scott, L.
Nabeta, P.
Demers, A.-M.
Reubenson, G.
Bosch, C.
David, A.
Van Der Zalm, M.
Havumaki, J.
Palmer, M.
Hesseling, A.C.
Ncayiyana, J.
Stevens, W.
Alland, D.
Denkinger, C.
Banada, P.
Date:
2018-01-01
Journal:
Journal of Clinical Microbiology
Content:
Identifiers:
Authors:
Geerts, C.C.
Grobbee, D.E.
Van Der Ent, C.K.
De Jong, B.M.
Van Der Zalm, M.M.
Van Putte-Katier, N.
Kimpen, J.L.L.
Uiterwaal, C.S.P.M.
Date:
2007-01-01
Journal:
Hypertension
Content:
Identifiers:
Authors:
Van Der Zalm, M.M.
Rossen, J.W.A.
Van Ewijk, B.E.
Wilbrink, B.
Van Esch, P.C.H.M.
Wolfs, T.F.W.
Van Der Ent, C.K.
Date:
2008-01-01
Journal:
Emerging Infectious Diseases
Content:
Identifiers:
Authors:
van der Zalm, M.M.
van Ewijk, B.E.
Wilbrink, B.
Uiterwaal, C.S.P.M.
Wolfs, T.F.W.
van der Ent, C.K.
Date:
2009-01-01
Journal:
Journal of Pediatrics
Content:
Identifiers:
Authors:
Date:
2021-01-05
Journal:
Respiration
Content:
An estimated 58 million people have survived tuberculosis since 2000, yet many of them will suffer from post-tuberculosis lung disease (PTLD). PTLD results from a complex interplay between organism, host, and environmental factors and affects long-term respiratory health. PTLD is an overlapping spectrum of disorders that affects large and small airways (bronchiectasis and obstructive lung disease), lung parenchyma, pulmonary vasculature, and pleura and may be complicated by co-infection and haemoptysis. People affected by PTLD have shortened life expectancy and increased risk of recurrent tuberculosis, but predictors of long-term outcomes are not known. No data are available on PTLD in children and on impact throughout the life course. Risk-factors for PTLD include multiple episodes of tuberculosis, drug-resistant tuberculosis, delays in diagnosis, and possibly smoking. Due to a lack of controlled trials in this population, no evidence-based recommendations for the investigation and management of PTLD are currently available. Empirical expert opinion advocates pulmonary rehabilitation, smoking cessation, and vaccinations (pneumococcal and influenza). Exacerbations in PTLD remain both poorly understood and under-recognised. Among people with PTLD, the probability of tuberculosis recurrence must be balanced against other causes of symptom worsening. Unnecessary courses of repeated empiric anti-tuberculosis chemotherapy should be avoided. PTLD is an important contributor to the global burden of chronic lung disease. Advocacy is needed to increase recognition for PTLD and its associated economic, social, and psychological consequences and to better understand how PTLD sequelae could be mitigated. Research is urgently needed to inform policy to guide clinical decision-making and preventative strategies for PTLD.
Identifiers:
DOI: 10.1159/000512531
Part of ISSN: 0025-7931
Part of ISSN: 1423-0356
Authors:
Date:
2021-01-15
Journal:
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Content:

Background

Limitations in the sensitivity and accessibility of diagnostic tools for childhood tuberculosis contribute to the substantial gap between estimated cases and cases notified to national tuberculosis programs. Thus, tools to make accurate and rapid clinical diagnoses are necessary to initiate more children on antituberculosis treatment.

Methods

We analyzed data from a prospective cohort of children <13 years being routinely evaluated for pulmonary tuberculosis in Cape Town, South Africa from March 2012 to November 2017. We developed a regression model to describe the contributions of baseline clinical evaluation to the diagnosis of tuberculosis using standardized, retrospective case definitions. We included results from baseline chest radiography and Xpert MTB/RIF to the model to develop an algorithm with at least 90% sensitivity in predicting tuberculosis.

Results

Data from 478 children being evaluated for pulmonary tuberculosis were analyzed (median age: 16.2 months, interquartile range: 9.8-30.9); 242 (50.6%) were retrospectively classified with tuberculosis, of which 104 (43.0%) were bacteriologically-confirmed. The area under the receiver operating characteristic curve for the final model was 0.87. Clinical evidence identified 71.4% of all tuberculosis cases in this cohort, and inclusion of baseline chest radiography results increased the proportion to 89.3%. The algorithm was 90.1% sensitive and 52.1% specific, and maintained a sensitivity of above 90% among children <2 years or with low weight-for-age.

Conclusions

Clinical evidence alone was sufficient to make most clinical antituberculosis treatment decisions. The use of evidence-based algorithms may improve decentralized, rapid treatment-initiation, reducing the global burden of childhood mortality.
Identifiers:
Authors:
Date:
2021-02-01
Journal:
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
Content:
Identifiers:
Authors:
Date:
2021-03-01
Journal:
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
Content:
Identifiers:
Authors:
Date:
2018-02-01
Journal:
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Content:
Background:Vaccination of human immunodeficiency virus (HIV)-infected infants with bacille Calmette-Guérin (BCG) is contraindicated. HIV-exposed newborns need a new tuberculosis vaccination strategy that protects against tuberculosis early in life and avoids the potential risk of BCG disease until after HIV infection has been excluded. Methods:This double-blind, randomized, controlled trial compared newborn MVA85A prime vaccination (1 × 108 PFU) vs Candin® control, followed by selective, deferred BCG vaccination at age 8 weeks for HIV-uninfected infants and 12 months follow-up for safety and immunogenicity. Results:A total of 248 HIV-exposed infants were enrolled. More frequent mild-moderate reactogenicity events were seen after newborn MVA85A vaccination. However, no significant difference was observed in the rate of severe or serious adverse events, HIV acquisition (n = 1 per arm), or incident tuberculosis disease (n = 5 MVA85A; n = 3 control) compared to the control arm. MVA85A vaccination induced modest but significantly higher Ag85A-specific interferon gamma (IFNγ)+ CD4+ T cells compared to control at weeks 4 and 8 (P < .0001). BCG did not further boost this response in MVA85A vaccinees. The BCG-induced Ag85A-specific IFNγ+ CD4+ T-cell response at weeks 16 and 52 was of similar magnitude in the control arm compared to the MVA85A arm at all time points. Proliferative capacity, functional profiles, and memory phenotype of BCG-specific CD4 responses were similar across study arms. Conclusions:MVA85A prime vaccination of HIV-exposed newborns was safe and induced an early modest antigen-specific immune response that did not interfere with, or enhance, immunogenicity of subsequent BCG vaccination. New protein-subunit and viral-vectored tuberculosis vaccine candidates should be tested in HIV-exposed newborns. Clinical Trials Registration:NCT01650389.
Identifiers:
Authors:
Chabala, C.
Turkova, A.
Thomason, M.J.
Wobudeya, E.
Hissar, S.
Mave, V.
van der Zalm, M.
Palmer, M.
Kapasa, M.
Bhavani, P.K.
Balaji, S.
Raichur, P.A.
Demers, A.-M.
Hoddinott, G.
Owen-Powell, E.
Kinikar, A.
Musoke, P.
Mulenga, V.
Aarnoutse, R.
McIlleron, H.
Hesseling, A.
Crook, A.M.
Cotton, M.
Gibb, D.M.
Date:
2018-01-01
Journal:
Trials
Content:
Identifiers:
Authors:
James A Seddon , author
Sarah Johnson , author
Megan Palmer , author
Marieke M van der Zalm , author
Elisa Lopez-Varela , author
Jennifer Hughes , author
H Simon Schaaf , author
Date:
2021-02-01
Journal:
Expert Review of Respiratory Medicine
Content:
Identifiers:
Authors:
De Jong, B.M.
Van Der Ent, C.K.
Van Putte Katier, N.
Van Der Zalm, M.M.
Verheij, T.J.M.
Kimpen, J.L.L.
Numans, M.E.
Uiterwaal, C.S.P.M.
Date:
2007-01-01
Journal:
Medical Care
Content:
Identifiers:
Authors:
Date:
2020-09-07
Journal:
The Pediatric infectious disease journal
Content:
Identifiers:
Authors:
van Ewijk, B.E.
van der Zalm, M.M.
Wolfs, T.F.W.
van der Ent, C.K.
Date:
2005-01-01
Journal:
Journal of Cystic Fibrosis
Content:
Identifiers:
Authors:
Van Ewijk, B.E.
Van Der Zalm, M.M.
Wolfs, T.F.W.
Fleer, A.
Kimpen, J.L.L.
Wilbrink, B.
Van Der Ent, C.K.
Date:
2008-01-01
Journal:
Pediatrics
Content:
Identifiers:
Authors:
Date:
2021-02-13
Journal:
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Content:
Globally, there are prevailing knowledge gaps in the epidemiology, clinical manifestations, and outcomes of SARS-CoV-2 infection among children and adolescents; however, these gaps are especially wide in African countries. The availability of robust age-disaggregated data is a critical first step in improving knowledge on disease burden and manifestations of COVID-19 among children. Furthermore, it is essential to improve understanding of SARS-CoV-2 interactions with comorbidities and co-infections such as HIV, tuberculosis, malaria, sickle cell disease and malnutrition, which are highly prevalent among children in sub-Saharan Africa. The African Forum for Research and Education in Health (AFREhealth) COVID-19 Research Collaboration on Children and Adolescents is conducting studies across Western, Central, Eastern, and Southern Africa to address existing knowledge gaps. This consortium is expected to generate key evidence to inform clinical practice and public health policymaking for COVID-19, while concurrently addressing other major diseases affecting children in African countries.
Identifiers:
Authors:
Van Der Gugten, A.C.
Van Der Zalm, M.M.
Uiterwaal, C.S.P.M.
Wilbrink, B.
Rossen, J.W.A.
Van Der Ent, C.K.
Date:
2013-01-01
Journal:
Pediatric Infectious Disease Journal
Content:
Authors:
Walters, E.
Van Der Zalm, M.M.
Palmer, M.
Bosch, C.
Demers, A.-M.
Draper, H.
Goussard, P.
Schaaf, H.S.
Friedrich, S.O.
Whitelaw, A.
Warren, R.
Gie, R.P.
Hesseling, A.C.
Date:
2017-01-01
Journal:
Pediatric Infectious Disease Journal
Content:
Authors:
Walters, E.
Demers, A.-M.
van der Zalm, M.M.
Whitelaw, A.
Palmer, M.
Bosch, C.
Draper, H.R.
Gie, R.P.
Hesseling, A.C.
Date:
2018-01-01
Journal:
Journal of Clinical Microbiology
Content:
Identifiers:
Authors:
Date:
2021-04-05
Journal:
Pediatric pulmonology
Content:

Introduction

Bronchoscopy can be a useful tool in children with pulmonary tuberculosis (PTB) with severe disease potentially requiring intervention or in the face of diagnostic dilemmas. The aim of this study was to determine the value of Xpert MTB/RIF assay (Xpert) on bronchoalveolar lavage (BAL) samples in children with complicated PTB.

Methods

Retrospective analysis of children with clinically diagnosed PTB, who underwent routine bronchoscopy over a five year period at a large referral hospital. BAL and other respiratory samples were tested by microscopy, culture and Xpert. We explored whether clinical, radiographic and bronchoscopy findings, and duration of antituberculosis treatment were associated with bacteriological confirmation.

Results

112/146 (76.7%) children (median age 16 months) were on antituberculosis treatment for a median of 10 days at the time of bronchoscopy. Overall, bacteriological confirmation was achieved in 115 (78.7%), with 101 (69.2%) detected on BAL. Of those bacteriologically confirmed on BAL, 61.4% were positive by both Xpert and culture, 34.7% only by Xpert and 3.9% only by culture. Sensitivity and specificity of Xpert compared to culture on BAL samples for children not on antituberculosis treatment were 94.1% (95% CI 71.3, 99.8) and 68.7% (95% CI 41.3, 89.0), respectively.

Conclusions

In children undergoing bronchoscopy for complicated PTB, Xpert testing of BAL had a high diagnostic yield in children already on antituberculosis treatment. Bronchoscopy should be considered if non-invasive respiratory specimens fail to confirm complicated TB. This article is protected by copyright. All rights reserved.
Identifiers:
Authors:
Date:
2020-11-10
Journal:
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Content:
BACKGROUND:Children seem relatively protected from serious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) related disease, but little is known about children living in settings with high tuberculosis and HIV burden. This study reflects clinical data on South African children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS:We collected clinical data of children aged younger than 13 years with laboratory confirmed SARS-CoV-2 presenting to Tygerberg Hospital, Cape Town between 17th of April and 24th of July 2020. RESULTS:Hundred and fifty-nine children (median age 48·0 months (interquartile range, IQR 12·0-106·0)) were included. Hospitalized children (n=62), median age of 13·5 months (IQR 1·8-43·5) were younger than children not admitted (n=97), median age 81·0 months (IQR 34·5-120·5, p< 0·01). Thirty-three of 159 (20·8%) children had pre-existing medical conditions. Fifty-one of 62 (82·3%) hospitalized children were symptomatic; lower respiratory tract infection was diagnosed in 21/51 (41·2%) and 11/16 (68·8%) children younger than 3 months of age. Respiratory support was required in 25/51 (49·0%) children; 13/25 (52·0%) children were younger than 3 months. One child was HIV infected and 11/51 (21·2%) were HIV exposed uninfected and 7/51 (13·7%) children had a recent or new diagnosis of tuberculosis. CONCLUSION:Children less than 1 year of age hospitalized with SARS-CoV-2 in Cape Town frequently required respiratory support, the access to oxygen may be limited in some LMICs which could potentially drive morbidity and mortality. HIV infection was uncommon but a relationship between HIV exposure, tuberculosis and SARS-CoV-2 should be explored.
Identifiers:
Authors:
Date:
2021-03-10
Journal:
The Lancet. Global health
Content:
Identifiers:
Authors:
van de Pol, A.C.
van der Zalm, M.M.
Jansen, N.J.G.
van der Ent, C.K.
van Loon, A.M.
Kimpen, J.L.L.
Rossen, J.W.A.
Rovers, M.M.
Wolfs, T.F.W.
Date:
2010-01-01
Journal:
Current Respiratory Medicine Reviews
Content:
Identifiers:
Authors:
Allwood, B.
van der Zalm, M.
Makanda, G.
Mortimer, K.
Andre F.S., A.
Uzochukwu, E.
Denise, E.
Diane, G.
Graeme, H.
Olena, I.
Rupert, J.
Florian M., M.
Jamilah, M.
Stellah, M.
Sanne, V.K.
Andrea, R.
Ingrid, S.
Cari, S.
Dalene, V.D.
Naomi, W.
Robert, W.
Date:
2019-01-01
Journal:
The Lancet Infectious Diseases
Content:
Authors:
Date:
2020-08-01
Journal:
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
Content:
ALTHOUGH CURABLE, TB frequently leaves the individual with chronic physical and psycho-social impairment, but these consequences have been largely neglected. The 1st International Post-Tuberculosis Symposium (Stellenbosch, South Africa) was held to discuss priorities and gaps in addressing this issue. A barrier to progress has been the varied terminology and nomenclature, so the Delphi process was used to achieve consensus on definitions. Lack of sufficient evidence hampered definitive recommendations in most domains, including prevention and treatment of post-TB lung disease (PTLD), but the discussions clarified the research needed. A consensus was reached on a toolkit for future PTLD measurement and on PTLD patterns to be considered. The importance of extra-pulmonary consequences and progressive impairment throughout the life-course was identified, including TB recurrence and increased mortality. Patient advocates emphasised the need to address the psychological and social impacts post TB and called for clinical guidance. More generally, there is an urgent need for increased awareness and research into post-TB complications.
Identifiers:
Authors:
van der Zalm, M.M.
Uiterwaal, C.S.P.M.
de Jong, B.M.
Wilbrink, B.
van der Ent, C.K.
Date:
2006-01-01
Journal:
Journal of Allergy and Clinical Immunology
Content:
Identifiers:
Authors:
van der Zalm, M.M.
Wilbrink, B.
van Ewijk, B.E.
Overduin, P.
Wolfs, T.F.W.
van der Ent, C.K.
Date:
2011-01-01
Journal:
Journal of Clinical Virology
Content:
Identifiers:
Authors:
Walters, E.
Van Der Zalm, M.M.
Demers, A.-M.
Whitelaw, A.
Palmer, M.
Bosch, C.
Draper, H.R.
Schaaf, H.S.
Goussard, P.
Lombard, C.J.
Gie, R.P.
Hesseling, A.C.
Date:
2019-01-01
Journal:
Pediatric Infectious Disease Journal
Content:
Authors:
Walters, E.
Demers, A.-M.
Van Der Zalm, M.M.
Whitelaw, A.
Palmer, M.
Bosch, C.
Draper, H.R.
Gie, R.P.
Hesseling, A.C.
Date:
2017-01-01
Journal:
Journal of Clinical Microbiology
Content:
Identifiers:
Authors:
Date:
2021-02-25
Journal:
The Lancet. Infectious diseases
Content:

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.

Funding

UK Medical Research Council, the UK Department for International Development, the National Institute for Health Research, and the European and Developing Countries Clinical Trials Partnership.
Identifiers:
Authors:
Date:
2020-12-04
Journal:
BMC infectious diseases
Content:
Background: The presentation of pulmonary tuberculosis (PTB) in young children is often clinically indistinguishable from other common respiratory illnesses, which are frequently infections of viral aetiology. As little is known about the role of viruses in children with PTB, we investigated the prevalence of respiratory viruses in children with suspected PTB at presentation and follow-up.

Methods: In an observational cohort study, children < 13 years were routinely investigated for suspected PTB in Cape Town, South Africa between December 2015 and September 2017 and followed up for 24 weeks. Nasopharyngeal aspirates (NPAs) were tested for respiratory viruses using multiplex PCR at enrolment, week 4 and 8.

Results: Seventy-three children were enrolled [median age 22.0 months; (interquartile range 10.0-48.0); 56.2% male and 17.8% HIV-infected. Anti-tuberculosis treatment was initiated in 54.8%; of these 50.0% had bacteriologically confirmed TB. At enrolment, ≥1 virus were detected in 95.9% (70/73) children; most commonly human rhinovirus (HRV) (74.0%). HRV was more frequently detected in TB cases (85%) compared to ill controls (60.6%) (p = 0.02). Multiple viruses were detected in 71.2% of all children; 80% of TB cases and 60.6% of ill controls (p = 0.07). At follow-up, ≥1 respiratory virus was detected in 92.2% (47/51) at week 4, and 94.2% (49/52) at week 8.

Conclusions: We found a high prevalence of viral respiratory co-infections in children investigated for PTB, irrespective of final PTB diagnosis, which remained high during follow up. Future work should include investigating the whole respiratory ecosystem in combination with pathogen- specific immune responses.
Identifiers:
Authors:
Van Der Zalm, M.M.
Van Soelen, N.
Mandalakas, A.M.
Jacobsen, M.
Detjen, A.K.
Marx, F.M.
Grewal, H.M.S.
Cotton, M.F.
Walzl, G.
Hesseling, A.C.
Date:
2017-01-01
Journal:
Pediatric Infectious Disease Journal
Content:
Authors:
Date:
2020-11-11
Journal:
JMIR mHealth and uHealth
Content:
Tuberculosis is the number one infectious cause of death globally. Young children, generally those younger than 5 years, are at the highest risk of progressing from tuberculosis infection to tuberculosis disease and of developing the most severe forms of tuberculosis. Most current tuberculosis drug formulations have poor acceptability among children and require consistent adherence for prolonged periods of time. These challenges complicate children's adherence to treatment and caregivers' daily administration of the drugs. Rapid developments in mobile technologies and apps present opportunities for using widely available technology to support national tuberculosis programs and patient treatment adherence. Pilot studies have demonstrated that mobile apps are a feasible and acceptable means of enhancing children's treatment adherence for other chronic conditions. Despite this, no mobile apps that aim to promote adherence to tuberculosis treatment have been developed for children. In this paper, we draw on our experiences carrying out research in clinical pediatric tuberculosis studies in South Africa. We present hypothetical scenarios of children's adherence to tuberculosis medication to suggest priorities for behavioral and educational strategies that a mobile app could incorporate to address some of the adherence support gaps faced by children diagnosed with tuberculosis. We argue that a mobile app has the potential to lessen some of the negative experiences that children associate with taking tuberculosis treatment and to facilitate a more positive treatment adherence experience for children and their caregivers.
Identifiers:
PMID: 33174850
DOI: 10.2196/19154
Authors:
de Jong, B.M.
van der Ent, C.K.
van der Zalm, M.M.
van Putte-Katier, N.
Verheij, T.J.M.
Kimpen, J.L.L.
Uiterwaal, C.S.P.M.
Date:
2009-01-01
Journal:
Pharmacoepidemiology and Drug Safety
Content:
Identifiers:
Authors:
Van Der Zalm, M.M.
Uiterwaal, C.S.P.M.
Wilbrink, B.
Koopman, M.
Verheij, T.J.M.
Van Der Ent, C.K.
Date:
2011-01-01
Journal:
American Journal of Respiratory and Critical Care Medicine
Content:
Identifiers:
Authors:
Wademan, D.T.
Busakwe, L.
Nicholson, T.J.
Van Der Zalm, M.
Palmer, M.
Workman, J.
Turkova, A.
Crook, A.M.
Thomason, J.
Gibb, D.M.
Seeley, J.
Hesseling, A.
Hoddinott, G.
Date:
2019-01-01
Journal:
International Journal of Tuberculosis and Lung Disease
Content:
Identifiers:
Authors:
Bartels, M.
van der Zalm, M.M.
van Oirschot, B.A.
Lee, F.S.
Giles, R.H.
Kruip, M.J.H.A.
Gitz-Francois, J.J.J.M.
Van Solinge, W.W.
Bierings, M.
van Wijk, R.
Date:
2015-01-01
Journal:
Human Mutation
Content:
Identifiers:
Authors:
Ahmed, S.
Mvalo, T.
Akech, S.
Agweyu, A.
Baker, K.
Bar-Zeev, N.
Campbell, H.
Checkley, W.
Chisti, M.J.
Colbourn, T.
Cunningham, S.
Duke, T.
English, M.
Falade, A.G.
Fancourt, N.S.S.
Ginsburg, A.S.
Graham, H.R.
Gray, D.M.
Gupta, M.
Hammitt, L.
Hesseling, A.C.
Hooli, S.
Johnson, A.-W.B.R.
King, C.
Kirby, M.A.
Lanata, C.F.
Lufesi, N.
MacKenzie, G.A.
McCracken, J.P.
Moschovis, P.P.
Nair, H.
Oviawe, O.
Pomat, W.S.
Santosham, M.
Seddon, J.A.
Thahane, L.K.
Wahl, B.
Van Der Zalm, M.
Verwey, C.
Yoshida, L.-M.
Zar, H.J.
Howie, S.R.C.
McCollum, E.D.
Date:
2020-01-01
Journal:
BMJ Global Health
Content:
Identifiers:
Authors:
Date:
2020-08-07
Journal:
Pediatric pulmonology
Content:
INTRODUCTION:The coronavirus disease-2019 (COVID-19) era is a challenging time for respiratory teams to protect their patients and staff. COVID-19 is predominantly transmitted by respiratory droplets; in the clinical setting, aerosol generating procedures pose the greatest risk for COVID-19 transmission. Bronchoscopy is associated with increased risk of patient-to-health care worker transmission, owing to aerosolized viral particles which may be inhaled and also result in environmental contamination of surfaces. METHODS:We describe our experience with the use of modified full-face snorkeling masks for pediatric bronchoscopy procedures in four COVID-19 infected children when filtering facepieces/respirators were in limited supply. RESULTS:Bronchoscopy was urgently required in four children, and could not be delayed until COVID-19 test results were available. During the pandemic peak, when respirators were in short supply, modified full-face snorkel masks (SEAC Libera, SEAC, Italy) were worn by the bronchoscopy team. Each mask was fitted with an O-ring, adapter, and heat and moisture exchanger filter. To date, there have been no COVID-19 infections among the bronchoscopy team staff, whereas the overall Hospital staff COVID-19 prevalence rate has exceeded 13.5% (667/4949). CONCLUSION:Emergency bronchoscopy procedures on COVID-19 infected patients or patients with unknown infection status can be safely performed using modified full-face snorkel masks.
Identifiers:
Authors:
Van Der Zalm, M.M.
Uiterwaal, C.S.P.M.
Wilbrink, B.
De Jong, B.M.
Verheij, T.J.M.
Kimpen, J.L.L.
Van Der Ent, C.K.
Date:
2009-01-01
Journal:
Pediatric Infectious Disease Journal
Content:

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