Publications

Funding for clinical research |drugs, vaccines, microbicides, diagnostics | HIV/AIDS, tuberculosis, malaria, other infectious diseases |sub-Saharan Africa

EDCTP portfolio: Neglected infectious diseases

The STOP study is developing a convenient pill to improve control of parasitic worm infections in Africa.

Better tools for control of parasitic worm infections

One in four of the world’s population have parasitic worm infections, with the most deprived communities particularly badly affected. Worm infections affect children’s physical and mental development, and can have long-lasting impact on their success in life.

Control of parasitic worms is based on mass drug administration campaigns with albendazole and mebendazole, targeting pre-school and school-aged children. However, these drugs do not work against threadworm (Strongyloides stercoralis) and are losing their ability to kill whipworm (Trichuris trichiura). In addition, use of drugs individually increases the risk that parasites will develop resistance.

The challenge

The STOP study is exploring whether adding ivermectin will improve the effectiveness of mass drug administration campaigns. Ivermectin is effective against S. stercoralis and its activity against T. trichiura is enhanced when it is used in combination with albendazole. A combination approach would also reduce the risk of resistance development.

The STOP team has extensive experience of drug development and formulation for parasitic diseases. It will carry out a large-scale phase III trial comparing the parasite-clearance performance of a single tablet combining albendazole and ivermectin, given either as a single dose or in a three-dose regime, with the usual treatment with albendazole.

The project

The STOP study will generate key evidence to support a licensing decision on the albendazole–ivermectin co-formulation. The combination could improve the effectiveness of mass drug administration campaigns against common but neglected parasitic worm infections, and protect a vital drug against the development of resistance.

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

One in four of the world’s population have parasitic worm infections, with the most deprived communities particularly badly affected. Worm infections affect children’s physical and mental development, and can have long-lasting impact on their success in life.

Control of parasitic worms is based on mass drug administration campaigns with albendazole and mebendazole, targeting pre-school and school-aged children. However, these drugs do not work against threadworm (Strongyloides stercoralis) and are losing their ability to kill whipworm (Trichuris trichiura). In addition, use of drugs individually increases the risk that parasites will develop resistance.

The STOP study is exploring whether adding ivermectin will improve the effectiveness of mass drug administration campaigns. Ivermectin is effective against S. stercoralis and its activity against T. trichiura is enhanced when it is used in combination with albendazole. A combination approach would also reduce the risk of resistance development.

The STOP team has extensive experience of drug development and formulation for parasitic diseases. It will carry out a large-scale phase III trial comparing the parasite-clearance performance of a single tablet combining albendazole and ivermectin, given either as a single dose or in a three-dose regime, with the usual treatment with albendazole.

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 STOP study will generate key evidence to support a licensing decision on the albendazole–ivermectin co-formulation. The combination could improve the effectiveness of mass drug administration campaigns against common but neglected parasitic worm infections, and protect a vital drug against the development of resistance.

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