3SI-CONTROL

The challenge

Neglected tropical diseases are responsible for an enormous global burden of disease, affecting many millions of the poorest people globally, particularly children. Soil-transmitted helminths, a group of common parasitic worms, affect around 1.5 billion people, including more than 250 million in sub-Saharan Africa, while over 200 million people worldwide – more than 90% of them in Africa – are affected by schistosome (flatworm) infections. Although rarely deadly, these infections have multiple debilitating effects on health and can significantly impair child growth and development. The pork tapeworm Taenia solium-related morbidity is strongly associated with neurocysticercosis (NCC), a major cause of epilepsy and various neurological disorders within endemic regions.

Mass drug administration is the cornerstone of soil-transmitted helminth control, typically with albendazole or mebendazole. Recently, with EDCTP funding, a fixed-dose combination of albendazole with a second anti-parasite drug, ivermectin, has been shown to have significant benefits, demonstrating greater efficacy against Trichuris trichiura (whipworm) and extending protection to include Strongyloides stercoralis (threadworm). Separately, mass drug administration with praziquantel is used to control schistosomes. For T. solium there are currently no countries routinely implementing control. Nevertheless, praziquantel also impacts the adult tapeworm, and as such, integration of disease control should be considered. 

The project

The 3SI-CONTROL project is assessing whether it is possible to combine the new fixed-dose combination of albendazole and ivermectin with praziquantel, as part of integrated mass drug administration campaigns targeting multiple parasites. 

While efficacy is well-established for the individual drugs and initial results from trials of the new fixed-dose combination are highly promising, the safety of multi-drug mass drug administration, as well as its effectiveness in real-world settings, needs to be rigorously demonstrated. There is a risk that an inflammatory response to T. solium larvae might generate neurological symptoms in people with brain cysts.

The 3SI-CONTROL project is therefore carrying out a trial in Tanzania and Zambia that will involve around 10,000 people aged 5 years and older. Areas in the two countries will randomly introduce the fixed-dose combination and praziquantel, either given simultaneously or 14 days apart. Participants will be followed for 45 days to check for any adverse reactions, with any neurological symptoms being subject to in-depth analysis.

Moreover, the impact of joint administration on the community prevalence of T. solium, soil-transmitted helminths and schistosomes will be assessed in Zambia. In addition, the project includes a One Health dimension – impacts on the presence of tapeworm larvae in pig populations will also be assessed; typically, around one in three pigs are affected, acting as a source of human infections. 

The project also includes a solid implementation research component, identifying potential barriers and facilitators to the introduction of the integrated control programmes in Tanzania, Zambia and Mozambique, along with cost-effectiveness assessment and long-term impact modelling. This work will be used to develop country-specific implementation plans. Prototype testing of the implementation strategies will be conducted in Zambia, Tanzania, and Mozambique, followed by optimisation of the implementation strategies.  Finally, the project will also develop general guidance for introductions and policy briefs.

Impact

The 3SI-CONTROL project will provide key policy-relevant data on an integrated approach to parasitic worm control. It will:

• Demonstrate whether the new fixed-dose combination and praziquantel can be safely administered together.
• Provide evidence of their impact on multiple parasitic worm infections.
• Generate practical guidance to accelerate the development and implementation of integrated multi-parasite control programmes.
• Build capacity in three Global South countries

If safety is sufficiently guaranteed, the project could pave the way to integrated mass drug administration campaigns, providing people with protection against multiple parasitic worm infections, including tapeworm infections, which are currently not routinely targeted for mass control. This could enhance the quality of life and development of millions in sub-Saharan Africa.