Director: Prof Heather Zar, Contact: heather.zar@uct.ac.za, Tel: 27-21-658-5318.


Unit Profile

The MRC Unit on Child and Adolescent Health focuses on key health concerns affecting children and adolescents in South Africa and in Africa. A primary focus is on child lung health and the intersection of infection with emergence of chronic non-communicable diseases, addressing lung health from birth through adolescence. Studies focus on the epidemiology, aetiology and risk factors for acute and chronic lung disease and the impact of acute disease on child health and on development of chronic disease.  "Research encompasses a broad range of methodologies from epidemiology to clinical science to laboratory-based methods". 

Studies include:

Drakenstein Child Health Study (DCHS)

The DCHS is a multi-year birth cohort study following 1,000 mother child pairs. The purpose of the study is to investigate the epidemiology, aetiology and risk factors for childhood lower respiratory illness and the impact on child health, particularly the development of chronic respiratory disease. 

The study aims to investigate the role and interaction of potential risk factors covering 7 areas (environmental, infectious, nutritional, genetic, psychosocial, maternal and immunological) that may impact child health. Mothers were enrolled at 20-28 weeks gestation and children are followed.

To date, the DCHS has provided novel data on the epidemiology and early life determinants of childhood illness and the long-term impact of early exposures to inform interventions and policy. Research over the reporting period has investigated the association between early life exposures and NCD development through adolescence as the cohort enters adolescence (10-12 years of age).

The cohort provides innovative, longitudinal assessment of a range of clinical, molecular, environmental and socioeconomic variables impacting child health and the evolution of chronic disease in a low- and middle-income country setting.

Cape Town Adolescent Antiretroviral Cohort (CTAAC) Study

In the Cape Town Adolescent Antiretroviral Cohort (CTAAC), approximately, 300 perinatally HIV-infected adolescents (YPHIV) on antiretroviral therapy and 100 age-matched HIV-uninfected controls have been followed for ten years to investigate long-term health outcomes including cardiometabolic, respiratory, neurocognitive, behavioural, and psychosocial disease and progression during late childhood and adolescence.  In 2020, an additional group of horizontally HIV-infected adolescents (YNPHIV) were recruited into the cohort. 

A key focus has been on cardiometabolic health with cardiac magnetic resonance (CMR) has used to characterize perinatal HIV-related progressive Left Ventricular (LV) remodelling and subclinical cardiac fibrosis. Findings indicate that adolescents with HIV have higher subclinical cardiac fibrosis than HIV-seronegative youth. LV remodelling in PHIV was associated with disproportionate expansion of the non-contractile interstitium. These results highlight the importance of early screening and long-term monitoring for cardiovascular disease.

MRC TB-CHILD

The MRC TB-CHILD network aims to establish a platform for paediatric TB translational research between Red Cross War Memorial Children’s Hospital (University of Cape Town) and paediatric departments in the Eastern Cape at the Dora Nginza Hospital (Nelson Mandela University). Concurrent to the ongoing capacity development at the Eastern Cape sites, a TB diagnostic study is currently underway at our unit in Cape Town. The aim is to extend this study across the TB-CHILD Network sites. This study aims to improve diagnosis of paediatric TB by establishing the diagnostic value (sensitivity and sensitivity) of novel tests on different specimens. 

TB-RePORT study

Since 2016, the Red Cross site has been enrolling participants into a prospective cohort study with the aim of strengthening diagnosis of paediatric TB. The study contributes the only paediatric data to the REPORT South Africa consortium.  Currently the study is in its third iteration (Report-003), the project aims to improve diagnosis of childhood TB through testing of novel biomarkers. A primary focus has been on point-of-care testing and rapid diagnosis (within 1 day).

This research has pioneered the use of different specimens and novel techniques for TB in children. Key outputs have been pioneering the use of sputum induction for microbiological confirmation of TB in children, the first paediatric studies of the use of Xpert in children for rapid diagnosis and study of alternate imaging, biomarkers and immune responses in childhood TB. Findings have changed clinical practice with sputum induction now widely practiced and included in international guidelines for childhood TB; use of Xpert in WHO guidelines and strengthening of TB microbiologic diagnosis in children. 

R2D2 Kids

The R2D2 diagnostics cohort study at Dora Nginza Hospital investigates novel diagnostics in paediatrics contributing to a multi-country cohort of participants from Uganda and Mozambique. Comprehensive sampling is done as well as collection of cough and lung sounds. Novel platforms being used include: XpertUltra and Molbio (India), and Pluslife (China) PCR platforms to determine diagnostic yields of point of care tests as compared to gold standard methods. The aim of the study is to conduct large-scale validation studies of the diagnostic accuracy of design-locked novel TB tests in children with presumptive intrathoracic TB overall and in key sub-groups to inform policy development.

AI Diagnostics for the detection of Paediatric Tuberculosis

The EVAL-PAEDTBAID study is a two-staged cohort study that is being conducted in three sites, one from South Africa and two from Pakistan with the following aims:

  • To evaluate the diagnostic accuracy of a novel AI-based chest CXR interpretation software (qXR) in detecting pulmonary TB (PTB) in paediatric population using a prospective cohort sample. 
  • To collect high-quality paediatric TB data that is correctly categorized as per NIH case definitions.
  • To conduct a clinical performance assessment of the device by investigating, if by using AI, the performance of clinicians improves or not in PTB diagnostic workup in children. 

RSV Vaccine Studies

The site has been involved in enrolling two distinct populations (neonates and pregnant mothers) into Respiratory Syncytial Virus (RSV) randomised clinical trials since 2017. Over the years, the site’s work has contributed to results from both Phase IIb and Phase III trials including but not limited to the following studies: 

  • A Phase 2b/3 Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of MK-1654 in Healthy Pre-Term and Full-Term Infants (Asservo) (Completed in 2024)
  • A Phase 3, Multicenter, Randomized, Partially Blinded, Palivizumab-Controlled Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of MK-1654 in Infants and Children at Increased Risk for Severe RSV Disease (Ongoing)
  • A Phase 3, Randomized, Double-Blinded, Placebo-Controlled Trial to Evaluate the Safety, Tolerability, and Immunogenicity of Respiratory Syncytial Virus (RSV) Prefusion F Subunit Vaccine in Pregnant Participants Living with HIV and their Infants (Ongoing)
  • A Phase-IV individually randomized, placebo-controlled trial in Africa, to evaluate the safety of RSVA/B-preF vaccine in pregnant women and efficacy against severe RSV-associated lower respiratory tract infection in infants (Planned start in May 2025).

List of publications from a list of over 600:

  1. Zar HJ, Barnett W, Myer L, Stein DJ, Nicol MP. Investigating the early-life determinants of illness in Africa: the Drakenstein Child Health Study. Thorax. 2015;70(6):592-4. PMCID: PMC5107608.
  2. Martinez L, le Roux DM, Barnett W, Stadler At, Nicol MP, Zar HJ. Tuberculin Skin test conversion and primary progressive tuberculosis disease in the first 5 years of life: a birth cohort study from Cape Town, South Africa. Lancet Child Adolesc Health. 2018 Jan;2(1):46-55 PMCID: PMC5810304.
  3. McCready C, Haider S, Little F, Nicol MP, Workman L, Gray DM, Granell R, Stein DJ, Custovic A, Zar HJ. Early childhood wheezing phenotypes and determinants in a South African birth cohort: longitudinal analysis of the Drakenstein Child Health Study. Lancet Child Adolesc Health. 2023 Feb;7(2):127-135. doi: 10.1016/S2352-4642(22)00304-2. Epub 2022 Nov 23. PMID: 36435180.
  4. Wedderburn CJ, Bondar J, Lake MT, Nhapi R, Barnett W, Nicol MP, Goddard L, Zar HJ. Risk and rates of hospitalisation in young children: A prospective study of a South African birth cohort. PLOS Glob Public Health. 2024 Jan 17;4(1):e0002754.
  5. Nicol MP, Workman L, Isaacs W, Munro J, Black F, Eley B, Boehme CC, Zemanay W, Zar HJ. Accuracy of the Xpert MTB/RIF test for the diagnosis of pulmonary tuberculosis in children admitted to hospital in Cape Town, South Africa: a descriptive study. Lancet Infect Dis. 2011;11(11):819-24. PMID: 21764384 
  6. Zar HJ, Workman L, Isaacs W, Munro J, Black F, Eley B, Allen V, Boehme CC, Zemanay W, Nicol MP. Rapid molecular diagnosis of pulmonary tuberculosis in children using nasopharyngeal specimens. Clin Infect Dis. 2012;55(8):1088-95. PMID: 22752518  PMCID: PMC3529610
  7. Zar HJ, Workman L, Isaacs W, Dheda K, Zemanay W, Nicol MP. Rapid diagnosis of pulmonary tuberculosis in African children in a primary care setting by use of Xpert MTB/RIF on respiratory specimens: a prospective study. Lancet Global Health. 2013;1(2):e97-104. PMID: 25104164
  8. Nicol MP, Workman L, Prins M, Bateman L, Ghebrekristos Y, Mbhele S, Denkinger C, Zar H. Accuracy of Xpert MTB/RIF Ultra for the Diagnosis of Pulmonary Tuberculosis in Children. PIDJ. 2018 Oct;37(10):e261-e263.doi:10.1097/INF0000000000001960. E-pub 22 Feb 2018.
  9. Zar HJ, Brown G, Donson H, Brathwaite N, Mann MD, Weinberg EG. Home-made spacers for bronchodilator therapy in children with acute asthma: a randomised trial. Lancet. 1999;354(9183):979-82. PMID: 10501359.
  10. Ait-Khaled N, Odhiambo J, Pearce N, Adjoh KS, Maesano IA, Benhabyles B, Bouhayad Z, Bahati E, Camara L, Catteau C, El Sony A, Esamai FO, Hypolite IE, Melaku K, Musa OA, Ng'ang'a L, Onadeko BO, Saad O, Jerray M, Kayembe JM, Koffi NB, Khaldi F, Kuaban C, Voyi K, M'Boussa J, Sow O, Tidjani O, Zar HJ. Prevalence of symptoms of asthma, rhinitis and eczema in 13- to 14-year-old children in Africa: the International Study of Asthma and Allergies in Childhood Phase III. Allergy. 2007;62(3):247-58. PMID: 17298341.
  11. Beran D, Zar HJ, Perrin C, Menezes AM, Burney P, Forum of International Respiratory Societies working group. Burden of asthma and chronic obstructive pulmonary disease and access to essential medicines in low-income and middle-income countries. Lancet Resp Med. 2015;3(2):159-70. PMID: 25680912.
  12. Pavord ID, Beasley R, Agusti A, Anderson GP, Bel E, Brusselle G, Cullinan P, Custovic A, Ducharme FM, Fahy JV, Frey U, Gibson P, Heaney LG, Holt PG, Humbert M, Lloyd CM, Marks G, Martinez FD, Sly PD, von Mutius E, Wenzel S, Zar HJ, Bush A. After asthma: redefining airways diseases. Lancet. 2018 Jan 27;391(10118):350-400. 
  13. Horvath S, Stein DJ, Phillips N, Heany SJ, Kobor MS, Lin DTS, Myer L, Zar HJ, Levine AJ, Hoare J. Perinatally acquired HIV accelerates epigenetic aging in South African adolescents. AIDS. 2018 July 17;32(11):1465-1474. PMCID: PMC6026068.
  14. Hoare J, Fouche JP, Phillips N, Joska JA, Myer L, Zar HJ, Stein DJ. Structural brain changes in perinatally HIV-infected young adolescents in South Africa. AIDS. 2018 Nov 28;32(18):2707-2718. PMCID: PMC6506179.
  15. Frigati LJ, Brown K, Mahtab S, Githinji L, Gray D, Zühlke L, Nourse P, Stein DJ, Hoare J, Cotton MF, Myer L, Zar HJ. Multisystem impairment in South African adolescents with Perinatally acquired HIV on antiretroviral therapy (ART). J Int  AIDS Soc. 2019 Aug;22(8):e25386. PMCID: PMC6706702.  
  16. Githinji LN. Gray DM, Hlengwa S, Machemedze T, Zar HJ. Longitudinal Changes in Spirometry in perinatally HIV-infected South African adolescents on antiretroviral therapy. Clin Infect Dis. 2019 April 02. ciz255. PMID: 30938406. 

Grant Support

Our studies are funded by several major international and national funders including the Bill & Melinda Gates foundation; National Institutes of Health (NIH); National Research Foundation (NRF); South African Medical Research Foundation (SAMRC); CRDF Global (Civilian Research & Development Foundation); the National Institute for Communicable Diseases (NICD) and the Thrasher Foundation.