“
crucial in

widening African

children’s access

to antiretrovirals

”

Bringing antiretroviral drugs to children

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

The challenge

Malaria still kills more than 400,000 people a year, with 92% of deaths occurring in sub-Saharan Africa. However, with effective treatment and control measures already available, there is great potential to reduce these numbers and even to consider the possibility of elimination.

Rapid diagnostic tests have become a mainstay of malaria control. However, current tests, mostly based on detection of two key parasite antigens (known as HRP2 and LDH), have some drawbacks. For example, persistence of HRP2 after infection leads to false positives, while loss of the corresponding pfhrp2 gene in some areas can generate false negatives. Molecular testing would be more accurate but typically requires laboratory facilities.

The DIAGMAL project is evaluating a new point-of-care molecular test for malaria. Known as Mini-db-PCR-NALFIA, the diagnostic platform is battery operated, controlled by a mobile phone, has a simple readout, requires no cold chain, provides results within an hour, and can be used following limited training. Compared with other molecular tests, it has the advantage of not requiring a DNA extraction step, making it cheaper and easier to use.

The performance of the new diagnostic is being evaluated in five settings with different malaria transmission characteristics. These include areas with high malaria incidence, seasonal malaria transmission, high levels of pfhrp2 deletions, and low malaria transmission where elimination might be feasible. The diagnostic is also being tested at a range of sites in Kenya with different patterns of malaria transmission.

Mini-db-PCR-NALFIA is around 100 times more sensitive than currently used rapid diagnostic tests. Its performance will be compared with gold standard polymerase chain reaction (PCR) testing at central facilities. The project will also examine the costs of introduction, as well as practical factors affecting its implementation within national control programmes in the different settings. The project team also includes members with expertise in product registration, to facilitate the development of a dossier for regulatory approvals and WHO prequalification.

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.

The DIAGMAL project will provide data on a highly sensitive tool for malaria detection. It is likely to be of most value in situations where high sensitivity is important, for example when the number of cases is low, as in areas targeted for elimination. It could also be used in locations where other tools have been compromised, for example because of pfhrp2 deletions. With 18 countries already having plans for malaria elimination, it could therefore be a critical tool in future malaria control efforts.

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