Schistosomiasis—from immunopathology to vaccines

Abstract

Schistosomiasis (bilharzia) is a neglected tropical disease caused by trematode worms of the genus Schistosoma. The transmission cycle involves human (or other mammalian) water contact with surface water contaminated by faeces or urine, as well as specific freshwater snails acting as intermediate hosts. The main disease-causing species are S. haematobium, S. mansoni and S. japonicum. According to the World Health Organisation, over 250 million people are infected worldwide, leading to considerable morbidity and the estimated loss of 1.9 million disability-adjusted life years (DALYs), a likely underestimated figure. Schistosomiasis is characterised by focal epidemiology and an over-dispersed population distribution, with higher infection rates in children. Complex immune mechanisms lead to the slow acquisition of immune resistance, but innate factors also play a part. Acute schistosomiasis, a feverish syndrome, is most evident in travellers following a primary infection. Chronic schistosomiasis affects mainly individuals with long-standing infections residing in poor rural areas. Immunopathological reactions against schistosome eggs trapped in host tissues lead to inflammatory and obstructive disease in the urinary system (S. haematobium) or intestinal disease, hepatosplenic inflammation and liver fibrosis (S. mansoni and S. japonicum). An effective drugpraziquantel-is available for treatment but, despite intensive efforts, no schistosomiasis vaccines have yet been accepted for public use. In this review, we briefly introduce the schistosome parasites and the immunopathogenic manifestations resulting from schistosomiasis. We then explore aspects of the immunology and host-parasite interplay in schistosome infections paying special attention to the current status of schistosomiasis vaccine development highlighting the advancement of a new controlled human challenge infection model for testing schistosomiasis vaccines.

Oral Administration of Artemisone for the Treatment of Schistosomiasis: Formulation Challenges and In Vivo Efficacy

“…According to the UNHCO, over 250 million people are infected globally, and approximately 700 million are at risk in 74 countries where the infection is endemic. In sub-Saharan Africa, the disease causes over 200,000 deaths per year [1]. The current chemotherapy and prevention of schistosomiasis rely on two drugs only, oxamniquine and praziquantel.…”

Parasites and their protection against COVID-19- Ecology or Immunology?

“…Parasites have co-evolved with humans and thus far become proficient immune modulators. For instance, in schistosomiasis, there is a balance between type 1 and 2 immune response related cytokines (IFNγ, IL-4, IL-5, and IL-13) which are required to contain the Schistosome eggs in granulomas-and the immunoregulatory cytokines IL-10 which dampen these responses in order to limit immunopathology (21)(22)(23)(24). Additionally, individuals in malaria endemic regions with stable transmission exhibit clinical immunity to malaria.…”

Schistosoma haematobiumextracellular vesicle proteins confer protection in a heterologous model of schistosomiasis

“…Vaccination with any of the TSPs did not elicit significant reductions in worm burden compared to controls (except for MS3_01370 in trial 1), however, significant reductions in tissue egg burdens (both liver and intestinal) were observed in all groups of vaccinated mice in both trials. Decreases in tissue egg loads are arguably the most important hallmarks of an effective vaccine against schistosomiasis given that (1) pathology due to the disease is egg-induced [89] and (2) disease transmission is dependent on the excretion of eggs from the host into the environment [10], so a vaccine which reduces egg burden in the host would ameliorate both disease pathology and transmission.…”

“…Furthermore, praziquantel has shown reduced efficacy in field studies [7] and is not effective against the immature stages of the parasite [8,9]. Hence, a vaccine that reduces disease severity and/or reduces transmission is needed to control and eliminate schistosomiasis [10,11]. Despite efforts over decades, there is no licensed vaccine [1,12].…”

“…However, results from a phase 3 trial conducted from 2009 to 2012 in S. haematobium infected children did not report any significant efficacy due to the vaccine [13]. Therefore, it is important to continue identifying new target antigens in the effort to develop a vaccine against S. haematobium and the other species of schistosomes [10,12].…”