- Trials in setup
Impact of increased praziquantel frequency on childhood fibrosis in persistent schistosomiasis morbidity hotspots.
Periportal fibrosis is the severest pathology caused by schistosomiasis mansoni. Large fibrotic deposits in the liver can lead to portal hypertension and death by haematemesis. The cornerstone of disease control is annual preventative chemotherapy (PC) through mass administration (MDA) of the safe and efficacious drug praziquantel (PZQ). Working with the Schistosome Control Initiative, Uganda was one of the first countries to introduce MDA of PZQ, with the first communities receiving treatment in 2003 located on the shores of Lake Albert. The inhabitants of these fishing communities had very high infection intensities and a record in the 20th-century scientific literature of highly prevalent severe schistosomiasis. Responding to more recent reports in this area of high numbers of individuals attending health clinics with end-stage schistosomiasis, we recently conducted a parasitological and ultrasound screen in these fishing communities and found periportal fibrosis to be commonplace.
Worryingly fibrotic patterns are not restricted to those of the older generation, ruling out the scenario that the fibrosis is present due to childhood exposure amongst those too old to have received treatment through MDA when they were school-aged. Amongst the 910 school-aged children (aged 7-15yrs) examined in Hoima District, 82% were found to have ultrasound detectable periportal fibrosis and 31% had central fibrosis, the manifestation most likely to lead to increases in portal pressure. The longstanding current intervention strategy is therefore not preventing morbidity in this region, with an unacceptably high percentage of children presenting with severe periportal fibrosis, and those children with mild periportal fibrosis being at risk of progression towards more severe disease. Highlighting this is the finding that amongst the adults screened, 56% had central periportal fibrosis, 24% with grades considered very severe and likely to respond poorly to treatment with PZQ. This is despite concerted efforts to treat annually, with the latest reported community MDA coverage rates for the district being 81%.
An alternative to the standard annual treatment for areas of high persistent morbidity is desperately required if the target of good health for all and schistosomiasis control is to be met. Integrated approaches of MDA, WASH (water, sanitation and hygiene) and where appropriate, intermediate snail host control, are proposed long-term strategies to drive down transmission in hot-spots. However, where persistent morbidity occurs, disease control strategies that will have a more immediate effect are required to prevent further generations progressing to severe, difficult-to-treat schistosomiasis with potentially irreversible sequelae. Therefore, the aim of this trial is to evaluate whether increasing treatment frequency with praziquantel through school-based delivery strategies reduces the prevalence of childhood periportal fibrosis in schistosomiasis morbidity hot-spots after two years of intervention.
This is a phase IV, single-centre, randomised superiority trial that is blinded to the primary outcome assessors, but open-label to all other investigators and participants. We plan to include 600 participants in this trial. Participants will be enrolled prior to the start of the trial. The active treatment phase will last 2-years. All participants will be enrolled for the duration of the 2-year follow-up.
Main inclusion criteria
1. Have a parent/guardian who has given written/marked informed consent for the child to participate. 2. Given written/marked informed assent to participate. 3. Aged 6-14 years of age. 4. Born or resident within the community in which their school is situated for >=2 years
Main exclusion criteria
The presence of any of the following will preclude participant inclusion:
- History of facial oedema after treatment with praziquantel
- Known neurocysticercosis or intraocular cysticercosis
Funders and sponsors
Dr Shona Wilson
Senior Clinical Trial Coordinator: Dr Katrina Gatley
Telephone: 01223 216740 | Email: email@example.com