Dr Marieke van der Zalm

South Africa

EDCTP portfolio: Career Development Fellowships

Dr Marieke van der Zalm investigates the impact of Mycobacterium tuberculosis and other common bacterial and viral pathogens in young South African children.

The impact of lower respiratory tract infections in young children

Tuberculosis (TB) and acute pneumonia are important causes of morbidity and mortality in children in the developing world. Although the importance of viral and bacterial infections, including pulmonary TB during respiratory illnesses is well recognised, key questions regarding the long-term sequelae of these infections remain unclear. These are especially relevant in developing countries where the burden of these diseases is high. The challenge is to collect better data on lung function in young children living in low and middle-income countries.

The challenge

In a major recent advance, a portable device to measure lung function in infants and young children has been developed and validated. The Whistler LFMi® takes measurements using the single occlusion technique (SOT) and the interrupter resistance technique. Both measure airway resistance while the SOT also measures airway compliance during tidal breathing. It is the first handheld device for performing pulmonary function tests on babies and young children which can readily be used in clinical settings. Both techniques have been shown to be feasible and reliable in infants and young children in studies conducted in Europe.

Dr Van der Zalm’s study aims to investigate the impact of M. tuberculosis and other common bacterial and viral pathogens in young South African children by using this practical and novel tool for lung function measurements. Children will be classified into bacteriologically confirmed, clinically diagnosed TB and not TB (pulmonary TB excluded), with or without other respiratory pathogens. Both baseline and long-term lung function in these children after 6 months will be assessed. As early lung function is a predictor of lung function later in life, clinical and epidemiological research in young children with pulmonary TB and other respiratory pathogens may benefit substantially from lung function measurements to assess the functional impact of these infections.

The project

Improved knowledge of pulmonary TB and lung function impairment will allow for the development and implementation of possible preventative and therapeutic strategies in high-risk children. These include tailored anti-tuberculosis treatment approaches, targeted vaccination for influenza or respiratory syncytial virus, and immune-modulating antibiotics.

Impact


test the safety and efficacy of this new formulation in young children

Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

EDCTP portfolio: HIV & HIV-associated infections

The challenge

Tuberculosis (TB) and acute pneumonia are important causes of morbidity and mortality in children in the developing world. Although the importance of viral and bacterial infections, including pulmonary TB during respiratory illnesses is well recognised, key questions regarding the long-term sequelae of these infections remain unclear. These are especially relevant in developing countries where the burden of these diseases is high. The challenge is to collect better data on lung function in young children living in low and middle-income countries.

In a major recent advance, a portable device to measure lung function in infants and young children has been developed and validated. The Whistler LFMi® takes measurements using the single occlusion technique (SOT) and the interrupter resistance technique. Both measure airway resistance while the SOT also measures airway compliance during tidal breathing. It is the first handheld device for performing pulmonary function tests on babies and young children which can readily be used in clinical settings. Both techniques have been shown to be feasible and reliable in infants and young children in studies conducted in Europe.

Dr Van der Zalm’s study aims to investigate the impact of M. tuberculosis and other common bacterial and viral pathogens in young South African children by using this practical and novel tool for lung function measurements. Children will be classified into bacteriologically confirmed, clinically diagnosed TB and not TB (pulmonary TB excluded), with or without other respiratory pathogens. Both baseline and long-term lung function in these children after 6 months will be assessed. As early lung function is a predictor of lung function later in life, clinical and epidemiological research in young children with pulmonary TB and other respiratory pathogens may benefit substantially from lung function measurements to assess the functional impact of these infections.

The project

The later CHAPAS-3 trial compared the efficacy and safety of three fixed-dose combinations including two without stavudine (found to have some long-term side effects in adults, leading to a recommendation that its use be discontinued in children). The trial the first of its kind in Africa studied nearly 500 children at four sites in two African countries.

Improved knowledge of pulmonary TB and lung function impairment will allow for the development and implementation of possible preventative and therapeutic strategies in high-risk children. These include tailored anti-tuberculosis treatment approaches, targeted vaccination for influenza or respiratory syncytial virus, and immune-modulating antibiotics.

ratios forfixed-dose combinations and on appropriatedosage according to weight. 

The CHAPAS-3 trial confirmed the effectiveness of fixed-dose combinations, providing further impetus to the rollout of antiretrovirals to children. Its evidence on abacavir informed the WHO recommendation of abacavir-containing combinations for first-line therapy in children. Trial data have also been used to support applications for regulatory approval for new scored efavirenz tablets.

Impact

L’homme RF et al. Nevirapine, stavudine and lamivudine pharmacokinetics in African children on paediatric fixed-dose combination tablets. AIDS. 2008;22(5):557–65.

Mulenga V et al. Abacavir, zidovudine, or stavudine as paediatric tablets for African HIVinfected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial. Lancet Infect Dis. 2016;16(2):169–79.

WHO. Guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2010.

WHO. Consolidated guidelines on the use of antiretroviral drugs
for treating and preventing

HIV infection: Recommendations for a public health approach
(second edition). 2016

Projects: Children with HIV in Africa Pharmacokinetics and Adherence of Simple Antiretroviral Regimens (CHAPAS): CHAPAS-1 and -3

Project lead: Professor Chifumbe Chintu, University Teaching Hospital, Zambia (CHAPAS-1); Dr Veronica Mulenga, University Teaching Hospital, Zambia (CHAPAS-3)

Target population(s): Children with HIV

Sample size: 71 (CHAPAS-1); 480 (CHAPAS-3)

Countries involved: Ireland, the Netherlands, the UK, the USA, Zambia (CHAPAS-1); Uganda, Zambia (CHAPAS-3)

Project duration: 2005–2009 (CHAPAS-1); 2010 –2011 (CHAPAS-3)

EDCTP funding: €1.2M (CHAPAS-1); €4.6M (CHAPAS-3)

Total project funding: €1.2M (CHAPAS-1); €5.0M

About us

The European & Developing Countries Clinical Trials Partnership (EDCTP) is a public–public partnership between 14 European and 16 African countries, supported by the European Union. EDCTP’s vision is to reduce the individual, social and economic burden of poverty-related infectious diseases by affecting sub-Saharan Africa. EDCTP’s mission is to accelerate the development of new or improved medicinal products for the identification, treatment and prevention of infectious diseases, including emerging and re-emerging diseases, through pre- and postregistration clinical studies, with emphasis on phase II and III clinical trials. Our approach integrates conduct of research with development of African clinical research capacity and networking. The second EDCTP programme is implemented by the EDCTP Association supported under Horizon 2020, the European Union’s Framework Programme for Research and Innovation.

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