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.
Highlights
Schistosomiasis, caused by Schistosoma japonicum, threatened many millions of people in the People’s Republic of China
This study is the first to report on the outcomes of a controlled trial (CRT) to test a schistosomiasis transmission blocking vaccine in the field
The baseline survey included: (i) Collection of a human stool sample, which was tested for S. japonicum infection using the miracidial hatching test (MHT) [19], after which the Kato Katz thick smear technique was used on positive samples to determine the infection intensity [Geometric Mean Eggs per Gram (GMEPG)] [19]; (ii) A
Summary
Schistosomiasis, caused by Schistosoma japonicum, threatened many millions of people in the People’s Republic of China (P.R. China) prior to initiation of the national schistosomiasis control program in the 1950s when nation-wide surveys identified 12 provinces as endemic, mostly in the south, with 12 million people infected (600,000 advanced cases), and 100 million people at risk of infection [1, 2]. The national schistosomiasis control program for the P.R. China achieved transmission control by the mid-1980s, introduced mass chemotherapy and morbidity control by the early 2000s, and has transitioned to integrated control approach [3]. Over the 10 years, five provinces achieved the national transmission interruption target (i.e., zero infections in humans, animals and snails), with seven other provinces achieving the national transmission control target (i.e., infection prevalence of
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