Schistosomiasis is a parasitic infection that afflicts hundreds of millions, and kills hundreds of thousands every year. Despite a strong immune response, the parasitic worms live and reproduce in the body for years. There are two diagnosis for schistosomiasis depending on the severity of the immune response: acute or chronic schistosomiasis. Acute schistosomiasis is characterised by a debilitating fever that can occur before the peak of the infection at 6-8 weeks caused by an intense immune response. This acute response is uncommon in natives to endemic areas as a result of in-utero sensitization to the disease. Testing in mice has revealed that without this harmfull over-reaction by the immune system, patients would be more likely to die.
On the other hand, chronic schistosomiasis leads to fibrosis. Those affected by this variation of the disease are more likely to have a genetic predisposition to it, built up over generations of life in infected regions. Even if genetics play a role, the intensity of infection still varies from person to person regardless of which variety of the disease is present. Studies of mice have shown that the intensity of infection, which corresponds to survival rates, is also genetic, but tied to a different gene. The relevant gene, surprisingly, doesn’t relate to the Schistosome itself, but to dampening the inflammatory response. It isn’t tied to lymphocytes though. Right now, no one knows the impact of B-Cells on the disease.
Interestingly, Schistosomes don’t have the capacity to grow in labs. They can only live in live humans, which hints that they take subtle biological cues from their hosts to stay alive. By infecting immunodeficient mice with schistosomiasis, the disease died off quickly without input from the T Cells and MHC molecules of the mice. This relationship has been hard to explore, given as to how the difficulty of growing these flukes has led to few insights into how they interface with us on a molecular level. We have found one lead: a receptor on Schistosomes that can bind to our cytokines, hinting at further connection between their survival and our immune responses.
Since schistosomiasis is endemic to areas commonly afflicted with other tropical diseases, we need research to find out what the correlation between schistosomiasis’s effect on our immune system and susceptibility to other diseases is. From testing mice, it seems like infection with schistosomiasis makes the acquisition of malaria, hepatitis, and toxoplasmosis more likely. Dealing with schistosomiasis and AIDS at the same time would kill you, even if the signals mentioned above wouldn’t work for the schistosomiasis. It does seem that having an ongoing immune reaction to schistosomiasis is similar to having allergies, and that helminth infections and allergies are inversely proportional.
Since schistosomiasis affects primarily children, researchers have looked into the high infection and reinfection rate in children contrasted to adults and found that IgE works as a good protector against Schistosomes. Researching this further on mice has proved difficult due to our differing biologies. Currently the body only triggers an immune response when the Schistosomes lay an egg. Because we can’t attack their adult forms, it takes even longer to start a fight against these invaders. We can’t even use Toll-like Receptors on them because they can’t toll the sugars on the eggs, even if our T Cells can.
Right now, we have developed a working vaccine for schistosomiasis in mice, with plans to scale it up in the future, even if making a vaccine for such an ancient and resilient pathogen is a challenge. While the working rodent vaccine is meant for killing cercariae(a larval stage of Schistosomes), another in development has shown promise if we’re capable of mass production. This vaccine is different from almost all others: it seeks to prevent the symptoms of the disease rather than the infection itself. This vaccine would disrupt the immune response to the schistosomiasis, keeping your body from fighting itself, and keeping the disease from spreading with the right host input.
In summary, Schistosomes are a complicated species that we don’t know enough about. We don’t understand how they evade the immune system, we don’t understand how the body can react to them without dying most of the time, and we don’t understand how interconnected we get as pair of species. If we want to eliminate schistosomiasis, then we need to continue our research, and figure these worms out.
Article: The Immunobiology of Schistosomiasis, by Edward J. Pearce and Andrew S. MacDonald