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

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Bringing antiretroviral drugs to children

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

The challenge

Although commonly viewed as a lung infection, TB can also affect the brain and nervous system. The TB bacterium can infect the membranes surrounding the brain and nervous system, the meninges, causing potentially fatal tuberculous meningitis.

TB meningitis is the most severe form of TB affecting children. However, early symptoms are non-specific and meningitis has multiple possible causes. Furthermore, facilities for brain imaging and analysis of cerebrospinal fluid samples to aid diagnosis are not available in many sub-Saharan African settings, leading to long delays in diagnosis and start of treatment.

In his EDCTP Senior Fellowship, Dr Novel Chegou aims to work with colleagues in the Engineering Faculty of Stellenbosch University to develop a novel point-of-care test for TB meningitis.

Dr Chegou was involved in the EDCTP-funded AE-TBC project, which identified a set of host biomarkers associated with TB meningitis infections in adults. This led to the development of six- and seven-biomarker ‘biosignatures’ with good potential to be used diagnostically for TB meningitis in adults. The EDCTP-funded ScreenTB project is evaluating the potential of a point-of-care diagnostic based on these biosignatures to detect active TB.

Building on this experience, Dr Chegou is evaluating more than 50 host inflammatory biomarkers with the potential to form the basis of a similar point-of-care diagnostic for TB meningitis in children. His goal is to identify the most promising combination of three or four biomarkers to provide a reliable indicator of TB meningitis. Past work has identified a three-biomarker signature with potential to form the basis of a new test.

His colleagues in the Engineering Faculty have developed novel detection technology based on zinc oxide nanowires. Dr Chegou plans to work with colleagues in Engineering to develop a prototype diagnostic for TB meningitis for use on cerebrospinal fluid or blood samples. Its performance will be assessed on samples from 300 newly recruited children with suspected TB meningitis.

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.

Through his EDCTP Senior Fellowship, Dr Novel Chegou aims to develop a much-needed new diagnostic that would accelerate the detection of TB meningitis in children, enabling treatment to begin much sooner. Dr Chegou has gained extensive experience in previous EDCTP-funded TB biomarker projects, but this is his first major grant in his own name. The EDCTP fellowship is therefore providing an opportunity for Dr Chegou to establish his credentials as a research leader through additional technical training, mentoring and leadership skills development.

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