Field Testing Integrated Interventions for Schistosomiasis Elimination in the People's Republic of China: Outcomes of a Multifactorial Cluster-Randomized Controlled Trial

Abstract

Despite significant progress, China faces the challenge of re-emerging schistosomiasis transmission in currently controlled areas due, in part, to the presence of a range of animal reservoirs, notably water buffalo and cattle, which can harbor Schistosoma japonicum infections. Environmental, ecological and social-demographic changes in China, shown to affect the distribution of oncomelanid snails, can also impact future schistosomiasis transmission. In light of their importance in the S. japonicum , lifecycle, vaccination has been proposed as a means to reduce the excretion of egg from cattle and buffalo, thereby interrupting transmission from these reservoir hosts to snails. A DNA-based vaccine (SjCTPI) our team developed showed encouraging efficacy against S. japonicum in Chinese water buffaloes. Here we report the results of a double-blind cluster randomized trial aimed at determining the impact of a combination of the SjCTPI bovine vaccine (given as a prime-boost regimen), human mass chemotherapy and snail control on the transmission of S. japonicum in 12 selected administrative villages around the Dongting Lake in Hunan province. The trial confirmed human praziquantel treatment is an effective intervention at the population level. Further, mollusciciding had an indirect ~50% efficacy in reducing human infection rates. Serology showed that the SjCTPI vaccine produced an effective antibody response in vaccinated bovines, resulting in a negative correlation with bovine egg counts observed at all post-vaccination time points. Despite these encouraging outcomes, the effect of the vaccine in preventing human infection was inconclusive. This was likely due to activities undertaken by the China National Schistosomiasis Control Program, notably the treatment, sacrifice or removal of bovines from trial villages, over which we had no control; as a result, the trial design was compromised, reducing power and contaminating outcome measures. This highlights the difficulties in undertaking field trials of this nature and magnitude, particularly over a long period, and emphasizes the importance of mathematical modeling in predicting the potential impact of control intervention measures. A transmission blocking vaccine targeting bovines for the prevention of S. japonicum with the required protective efficacy would be invaluable in tandem with other preventive intervention measures if the goal of eliminating schistosomiasis from China is to become a reality.

Current Status of Schistosomiasis Control and Prospects for Elimination in the Dongting Lake Region of the People’s Republic of China

“…In addition, livestock containment, rigorous surveillance methods and the availability of more sensitive diagnostics will be paramount to achieve success ( 69 , 74 ). Vaccination of bovines and other reservoirs represents an important intervention to the schistosomiasis armory and may represent the best hope for achieving eventual elimination but, despite some encouraging recent progress ( 75 , 76 ), no such vaccine has been developed to an acceptable level for wide-scale use.…”

Schistosomiasis Elimination: Beginning of the End or a Continued March on a Trodden Path

“…Studies undertaken in PR China [34] and the Philippines [35] have identified bovines as major reservoir hosts for S. japonicum , and so have provided the rationale for a veterinary-based transmission-blocking vaccine targeting bovines in these settings, benefitting animals directly and humans indirectly. The SjCTPI vaccine [36] has shown promise in experimental trials, and field trials have recently been completed in PR China and the Philippines [37,38]. Interestingly, as shown by You et al [39] in this special issue, this kind of vaccine would also be useful in African countries although not for humans, only for animals.…”

Experimental Infection of the Biomphalaria glabrata Vector Snail by Schistosoma mansoni Parasites Drives Snail Microbiota Dysbiosis

“…At present, there is no effective vaccine against schistosomiasis and the treatment relies on a single chemotherapeutic treatment, Praziquantel [ 2 ], against which resistance has been observed [ 3 ]. Molluscicides have been also used to impair Schistosoma transmission in the field [ 4 ]. However, the dramatic effects of molluscicides on natural environments prompt us to seek new ways to prevent and/or control this disease in the field [ 5 ].…”