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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

Schistosoma haematobium infects more than 110 million individuals causing urinary schistosomiasis, which results in more than 150,000 deaths annually in tropical and sub-tropical countries. Several countries have started and others are about to start mass praziquantel administration in endemic areas. This approach is expensive and may be required for a long time. This places enormous demands on limited national resources. There is a need for accurate, easy-to-use, cheap and easily available tools to monitor the performance of such morbidity control programmes.

Infections with schistosomes result in cytokine-mediated urinary tract inflammation. These cytokines, particularly interleukin (IL)-6 and IL-10 are present in the urine of infected individuals and their levels reflect the intensity of the infection and the urinary tract pathology. The general objective is to assess urinary IL-6 and IL-10 ELISA as a tool for assessing S. haematobium-related urinary tract pathology before and after treatment in an S. haematobium-endemic community of Kenya. We will use a commercially available cytokine ELISA kit. Specific objectives are to 1) correlate levels of urinary IL-6 and IL-10 to S. haematobium-related pathology; 10 assess levels of urinary IL-6 and IL- 10 in relation to children’s age; 3) compare changes in urinary IL-6, IL-10 and ECP (eosinophil cationic protein) levels before and after treatment; 4) determine the rate of degradation of urinary IL-6 and IL-10 at selected temperature ranges.

Urine samples will be collected from S. haematobium-infected primary schoolchildren (308) and examined for S. haematobium eggs using microscopy, IL-6, IL-10 and ECP levels using ELISA at baseline and at 3, 12 and 24 months after baseline. The children will be treated with praziquantel before baseline and at 12 months after initial treatment (before the second follow-up sample collection). In addition, levels of urinary IL-6 and IL-10 will be compared in urine samples stored at -20 ºC, 4 ºC and 25 ºC for two weeks.

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.

Demonstrating that treatment success of S. haematobium-related urinary tract pathology can be successfully assessed using a commercially available cytokine ELISA kit, may validate a way to faster, easier and cheaper monitoring of control programmes involving mass drug administration.

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