Modelling livestock test-and-treat: A novel One Health strategy to control schistosomiasis and mitigate drug resistance

Abstract

Schistosomiasis, a neglected tropical disease, is a widespread chronic helminthiasis reported in 78 countries, predominantly those within sub-Saharan Africa, as well as Latin America, Asia, and most recently, even Europe. Species of the causative blood fluke infect not only humans but also animals, and hybrids between previously assumed human-specific and animal-specific schistosomes are being increasingly reported. Existing control programs across Africa focus on humans and rely heavily on mass drug administration of praziquantel, the sole drug available against schistosomiasis. Praziquantel is safe and highly efficacious but could become ineffective if resistance emerges. To reach the revised World Health Organization goal of elimination of schistosomiasis as a public health problem, and interruption of transmission within selected regions, by 2030, new consideration of the role of animal reservoirs in human transmission in general, and whether to also treat livestock with praziquantel in particular, has been raised. However, whilst there are no dedicated control programs targeting animals outside of Asia, there are emerging reports of the use and misuse of praziquantel in livestock across Africa. Therefore, to effectively treat livestock in Africa and to help mitigate against the potential evolution of praziquantel resistance, structured control strategies are required. Here, using a transmission modelling approach, we evaluate the potential effectiveness of a theoretical test-and-treat (TnT) strategy to control bovine schistosomiasis using a currently available point-of-care diagnostic test (developed for human use) to detect circulating cathodic antigen (POC-CCA). We show that implementing TnT at herd-level from 2022 to 2030 could be highly effective in suppressing infection in cattle and even, in lower prevalence settings, reaching nominal ‘elimination’ targets. We highlight the importance of enhancing the specificity of POC-CCA for use in livestock to avoid unnecessary treatments and discuss the outstanding challenges associated with implementing TnT as part of a holistic One Health approach to tackling human and animal schistosomiasis.

Reaching the World Health Organization elimination targets for schistosomiasis: the importance of a One Health perspective

“…for S. haematobium clade human infection caused by interspecific hybrids in Senegal [105]) have been reported.veterinary use of anthelminticsThe use of anthelmintics in the veterinary field is thought to increase the risk of emerging drug resistance [34], owing in part to the unstructured way in which drugs are administered in some settings. A structured test-and-treat approach [100] has potential to partly counteract such risks, although the risk of emerging resistance can never be completely avoided [102]. Notwithstanding, even after decades of extensive praziquantel use in livestock in China, no evidence of drug resistance under field conditions has been reported to date [102].…”

“…The use of praziquantel for livestock schistosomiasis is already thought to be widespread in parts of SSA [ 34 , 99 ], but misuse is reported widely, with farmers often employing subtherapeutic doses, inappropriate products instead of suitable veterinary formulations, and incomplete treatment regimens. Thus, while there exists demand for livestock schistosomiasis control, there is a need for a structured approach [ 100 ]. Initial exploration of a herd-level test-and-treat (TnT) approach for cattle using a mathematical transmission model suggests that up to 75% of bovine case-years in highly endemic settings and up to 85% of bovine case-years in lower transmission contexts could be averted [ 100 ].…”

“…Thus, while there exists demand for livestock schistosomiasis control, there is a need for a structured approach [ 100 ]. Initial exploration of a herd-level test-and-treat (TnT) approach for cattle using a mathematical transmission model suggests that up to 75% of bovine case-years in highly endemic settings and up to 85% of bovine case-years in lower transmission contexts could be averted [ 100 ]. The potential impact of TnT interventions could thus be substantial.…”

“…The potential impact of TnT interventions could thus be substantial. There remain several outstanding challenges before TnT interventions could be implemented, including the availability of sensitive and specific point-of-care diagnostics [ 3 , 75 ] (see [ 101 ] for a systematic review and meta-analysis of diagnostics for non-human schistosomiasis) and suitable veterinary formulations [ 100 ]. Moreover, a TnT approach can only partially mitigate the risk of promoting drug resistance, an ominous spectre given the exclusive reliance on praziquantel for the treatment of human and animal schistosomiasis ( table 2 ).…”

Modeling the effectiveness of One Health interventions against the zoonotic hookworm Ancylostoma ceylanicum

“…Numerous authors have advocated the use of a “One Health” approach to tackle A. ceylanicum hookworm ( 9 – 11 , 14 , 15 ) and indeed the WHO 2030 road map acknowledges the importance of One Health for other NTDs such as rabies, taeniasis, and cystic echinococcosis ( 1 ). Such an approach would likely involve expansion of mass drug administration (MDA) to domestic and stray cat and dog populations in settings where A. ceylanicum is endemic ( 15 ), similar to proposals to tackle zoonotic schistosomiasis in Africa by treating livestock ( 16 , 17 ) and the existing strategy in China where animals are recognized as key to eliminating Schistosoma japonicum ( 18 ). Although there exist a number of highly efficacious treatment options for hookworm in cats and dogs—including “spot-on” topical treatments ( 19 – 21 )—there is currently no empirical evidence on the likely effectiveness of a One Health approach.…”