Schistosome Research: Using basic biological research to fight schistosomiasis

Schistosomes infect over 200 million of the world's poorest people

Schistosomes are parasitic flatworms that cause disease and death in millions of people. These parasites infect people in parts of South America and Asia, but the overwhelming majority of infections occur in sub-Saharan Africa. The disease these parasites cause is called Schistosomiasis (a.k.a Bilharzia or Snail Fever). Schistosomiasis is just one of a group of diseases known as Neglected Tropical Diseases (NTDs) that disproportionately affect the world’s poorest and most vulnerable people.

Here in the Collins Lab, we believe that understanding the basic biology of this organism is key to developing the next generation of anti-schistosome drugs and vaccines. We also contend that by studying the basic biology of these fascinating organisms, we can better understand important basic biological processes common to all animals, including humans. For that reason, we study schistosomes from multiple angles using a variety of modern molecular approaches.

What is a schistosome?

Schistosomes are flatworms but come in all shapes and sizes depending on which stage of their lifecycle they are in. Hover over each image to discover out what each image represents.

Scanning Electron Micrograph of a Miracidium Confocal Micrograph of developing Cercariae inside a Sporocyst growing in a snail Scanning Electron Micrograph of a Cercaria Scanning Electron Micrograph of a male and female worm Artistic rendering of showing stem cells under the skin of a male schistosome Confocal Micrograph of Mehlis’ Gland and an egg Scanning Electron Micrograph of a Miracidium Confocal Micrograph of developing Cercariae inside a Sporocyst growing in a snail Scanning Electron Micrograph of a Cercaria Scanning Electron Micrograph of a male and female worm

What are the symptoms of schistosomiasis?

Although schistosomes are thought to kill an estimated 250,000 people every year, perhaps the greatest tragedy is the chronic disability associated with infection. Those with the most serious symptoms are often children who can suffer from malnutrition, anemia, stunted cognitive and physical development, physical pain/discomfort, and chronic inflammation. Diseases like schistosomiasis may also enhance the probability of contracting diseases like HIV/AIDS though sexual contact. The cumulative effect is that those who are chronically infected are effectively robbed of their ability to lead productive lives, condemning themselves (and likely their families) to a life of poverty. Being impoverished then enhances the likelihood that these people are exposed to diseases like schistosomiasis. This perpetuates a seemingly endless cycle of disease and poverty.

What is the treatment for schistosomiasis?

Treatment of schistosomiasis relies on a single drug called Praziquantel. While Praziquantel is effective at clearing a schistosome infection it is far from a magic bullet. Praziquantel doesn’t prevent people from becoming re-infected next time they step into the water and there is concern that resistance to the drug may arise. It is clear that ridding the world of schistosomes will require the implementation of multiple strategies including (but not limited to): the development of new drugs and/or vaccines, improved sanitation, control of the snail populations, and education in the developing world about how the disease is transmitted.

Meet the Collins Lab Team


The Collins Lab is committed to understanding the amazing biology of schistosomes. They hope these insights will lead to new treatments to help those negatively affected by schistosomiasis. In this section, you can learn all about each member of the lab. If you are interested in discussing the possibility of you working here at the Collins Lab, please contact us.

Dr. James J. Collins, III

Jim Collins received his BS in Biology from Southeast Missouri State University (2003) and PhD from Washington University in St. Louis (2008). He did postdoctoral work with Phillip Newmark (Howard Hughes Medical Institute) at the University of Illinois at Urbana-Champaign.

His research focuses on the basic biology parasitic flatworms called schistosomes. These parasites infect more than 200 million of the world's poorest people, causing morbidity that rivals global killers including Malaria and TB. Despite their devastating global impact, only a single drug is available to treat schistosome infection. As a postdoc he developed new functional genomic tools to study these worms and using these tools discovered a novel population of stem cells that are likely key to parasite survival inside their human host. By studying these stem cells, and applying large-scale functional genomic approaches, his work aims to develop new therapeutic avenues to combat these devastating parasites.

  • Scientific Interests: Germ cells, Parasite Biology, Regeneration, Stem Cells

The Team


Julie Collins, M.S.


Megan McConathy


Aracely Romero


George Wendt


Jipeng Wang, Ph.D.

Frequently Asked Questions about Schistosomes


In the Collins Lab, we know from countless family gatherings, parties, and class reunions, that almost everyone is curious about schistosomes. That being so, we have created a comprehensive list of some of the most frequently asked schistosome-related questions.

What are schistosomes?

Schistosomes are parasitic Platyhelminthes (or flatworms) that infect over 200 million people. Although these parasites infect people in parts of South America and Asia the overwhelming majority of infections occur in sub-Saharan Africa. The disease these parasites cause is called Schistosomiasis (a.k.a Bilharzia or Snail Fever). Schistosomiasis is just one of a group of diseases known as Neglected Tropical Diseases (NTDs) that disproportionately affect the world’s poorest and most vulnerable people.

How do people get infected with schistosomes?

People get infected with schistosomes when they come into contact with water contaminated with larval parasites, called cercariae. These cercariae are able to sense people in the water and rapidly pierce through their skin. One inside the skin, the parasites migrate to the blood and begin developing as male or female worms.

Where do these infective cercariae come from?

It’s complicated. Schistosomes have a life-cycle that includes both mammalian and snail hosts. Inside the blood of their human host, male and female worms mate and produce eggs. These eggs are then excreted in the host’s the feces or urine. Since many of those infected live in parts of the world with poor sanitation, their waste products that contain schistosome eggs have the opportunity to reach nearby fresh water lakes or streams. Once in the water these eggs hatch, liberating another larval form called miracidia. These miracidia then seek out and infect a suitable snail host. Inside the snail these miracidia that have the ability to make thousands of genetic copies of themselves that develop into cercariae capable of infecting humans.

How do schistosomes make people sick?

Oddly enough, having schistosome worms living in your blood vessels is not what makes you sick. It turns out the main driver of disease is the massive egg output of the female schistosome: she can lay an egg every one to five minutes! Although some of these eggs are excreted via the host urine or feces, many are washed away in the bloodstream and ultimately become trapped in your organs (e.g., the liver or bladder). These eggs induce immune responses that can lead to serious complications including organ failure, internal bleeding, and even cancer. Unfortunately, some of the effects of schistosome infection can persist long after the parasites have been killed (e.g., following drug treatment). Our group is actively trying to understand schistosome reproductive biology with the hope this could lead to new ways to curb the spread of the parasite and also alleviate the pathology of the disease.

If you are infected will the parasites ever go away?

The lifespan of the schistosome inside a human host is a very hard thing to address. However, there are countless cases of people harboring active schistosome infections 20-30 years after moving endemic parts of the world (e.g., Africa) to a non-endemic region (e.g., the United States of Europe). Therefore, schistosomes seem to be capable of surviving for decades inside your body. How these parasites are able to do this is a question our team is actively exploring.

What are the symptoms of schistosome infection?

The symptoms vary depending on the type of schistosome someone is infected with. In Africa, two species dominate: Schistosoma mansoni and Schistosoma haematobium. In Asia, S. japonicum is the most prevalent. Both S. mansoni and S. japonicum live in the blood vessels near the intestine and can cause symptoms including bloody stool, abdominal pain, liver fibrosis, liver cirrhosis, portal hypertension, splenomegaly, and ascites (a swollen belly due to fluid accumulation). In S. haematobium infections the symptoms are associated with the urinary tract and include bloody urine (haematuria), infertility, bladder fibrosis, kidney damage, and bladder cancer.

What happens to people that are infected with schistosomes?

Although schistosomes are thought to kill an estimated 250,000 people every year, perhaps the greatest tragedy is the chronic disability associated with infection. Those with the most serious symptoms are often children who can suffer from malnutrition, anemia, stunted cognitive and physical development, physical pain/discomfort, and chronic inflammation. Diseases like schistosomiasis may also enhance the probability of contracting diseases like HIV/AIDS though sexual contact. The cumulative effect is that those who are chronically infected are effectively robbed of their ability to lead productive lives, condemning themselves (and likely their families) to a life of poverty. Being impoverished then enhances the likelihood that these people are exposed to diseases like schistosomiasis. This perpetuates a seemingly endless cycle of disease and poverty.

Is there a cure?

Treatment of schistosomiasis relies on a single drug called Praziquantel. While Praziquantel is effective at clearing a schistosome infection it is far from a magic bullet. Praziquantel doesn’t prevent people from becoming re-infected next time they step into the water and there is concern that resistance to the drug may arise. It is clear that ridding the world of schistosomes will require the implementation of multiple strategies including (but not limited to): the development of new drugs and/or vaccines, improved sanitation, control of the snail populations, and education in the developing world about how the disease is transmitted.

Are there schistosomes in the United States?

Yes! Fortunately, in the United States these schistosomes are only capable of infecting birds. However, if you were to come into with the cercariae of these bird schistosomes you would get an rash known as swimmers itch or cercarial dermatitis. However, as the earth gets warmer due to climate change there is the possibility that diseases like schistosomiasis could widen their reach. Indeed, there have been recent outbreaks of S. haematobium infections in the French island of Corisica, where schistosomes had not previously been known to exist.

I think I’m infected; can you help or diagnose me?

We are researchers, not licensed physicians, and are not qualified to provide medical advice. I suggest you to contact your local health care provider and have them conduct the proper tests.

How does your lab study this problem?

We believe that understanding the basic biology of this organism is key to developing the next generation of anti-schistosome drugs and/or vaccines. We also contend that by studying the basic biology of these fascinating organisms we can better understand important basic biological processes common to all animals, including humans. Therefore, we are trying to study schistosomes from multiple angles using a variety of modern molecular approaches.

Schistosomes sound really important and equally interesting, is this something that I can study in my lab?

That's excellent news! The field will really benefit from new people brining their enthusiasm and experimental skillsets to bear on studying these parasites. The most challenging barrier to working on schistosomes is maintaining these parasites in the lab which requires maintaining both snail and mammalian hosts. Fortunately, there are people ready to help! Indeed, the National Institutes of Health supports the Schistosome Resource Center at the Biomedical Research Institute in Rockville, MD. This resource provides infected snails and mice/hamsters to investigators for a nominal fee. They also provide training to investigators wishing to learn more about working on schistosomes. For more information, visit their website or read about this resource in a review by Fred Lewis et al. published in PLoS NTDs .

I'm working on schistosomes, do you have any protocols you can share?

Yes! We've developed a Protocols section that includes some of our bread and butter approaches for studying schistosomes in the lab. Feel free to use these for your own work, if you find any improvements or suggestions for additional protocols, let us know . Also, since these protocols have been painstakingly developed not only by our lab but also by many others, make sure to acknowledge the appropriate authors by citing them in your publications.

How can I help?

Spreading the word to raise awareness about Neglected Tropical Diseases like Schistosomiasis is a great place to start. If you are in the United States, you can also contact your Congressional representatives in the House and Senate and tell them you support basic research and increased funding for the National Institutes of Health and National Science Foundation. Basic scientific and biomedical research absolutely relies on funding from the federal government.

Schistosome Research


Schistosomiasis is among the most prevalent human parasitic diseases, affecting more than 200 million of the world's poorest people, largely in sub-Saharan Africa. Although recent estimates suggest the disease-associated disability due to schistosomiasis may rival malaria or tuberculosis, only a single therapeutic agent (praziquantel) is available to treat this disease. The etiological agents of schistosomiasis are parasitic flatworms (Schistosoma or blood flukes) that enter the host following exposure of skin to freshwater contaminated with larval schistosomes. Once in the host these parasites develop and eventually reside in the vasculature where they live and reproduce. These worms produce hundreds to thousands of eggs per day, many of which lodge in host tissues causing chronic symptoms that can persist for decades.

With the looming danger that praziquantel-resistant Schistosoma strains will emerge, an urgent need exists to identify novel therapeutic agents to combat these parasites. Thus, we are leveraging our experience in developmental biology and functional genomics to address long-standing gaps in our knowledge of schistosome biology. Focusing on the biology of stem cells in the adult parasite and functional genomic approaches to identify novel therapeutic targets we hope to make important contributions towards eradicating these devastating parasites. We believe this system provides a fantastic opportunity to ask basic biological questions and channel what we learn as a means to directly improve human health.

Biology of Schistosome Stem Cells

A central theme of our lab is that schistosomiasis is fundamentally a disease of stem cells: stem cells in the germline produce eggs that cause host pathology and somatic stem cells rejuvenate parasite tissues allowing these worms to survive in their host for years. Therefore, we are using a growing set of molecular tools to study schistosomes to begin to understand what factors regulate the function of the various stem cell populations in these parasites. We expect this line of investigation to open up new avenues to develop therapeutics while simultaneously enriching our understanding of how stem cell function is regulated on a molecular level.

Large-scale analyses of gene function

There are now genome sequences for all the major schistosome species that infect humans, yet we only know the function of a small handful of genes in these parasites. Thus, we are employing large-scale approaches to begin to ascribe function to genes in the S. mansoni genome. These approaches hope to uncover gene products or biochemical pathways that can be exploited for the development of a new generation of anti schistosome therapeutics.

Comparative Biology and Evo-Devo

Schistosomes are members of the phylum Platyhelminthes (flatworms) that includes both free-living (e.g., planarians) and parasitic (e.g., tapeworms) taxa. In spite of their complicated lifecycles, parasitic flatworms (also known as the neodermata) represent the most successful and species dense group of flatworms. In fact, no vertebrate species on earth escapes parasitism by a least one species of parasitic flatworms. A common feature to most members of this phylum is a presence of a population of somatic stem cells called neoblasts. These cells fuel regeneration in organisms like planarians, underlie the massive growth of tapeworms, and we recently discovered a population of these cells in schistosomes. Given these cells are ubiquitous among not just free-living flatworms, but also parasitic flatworms, we are interested in testing the hypothesis that neoblasts were an evolutionary force that led to the emergence and success of the parasitic flatworms.

The Biology of the Schistosome Tegument

Schistosomes can thrive in the blood for decades and appear to completely resist the onslaught of the host immune response. How do these parasites accomplish this? As a large foreign object in the blood how are they not “rejected” like a transplanted organ? Recently, we demonstrated that the schistosome somatic stem cells are biased towards the production of cells associated with the surface of the parasite, a structure called the tegument. The tegument is widely believed to be key for the schistosome’s ability to evade the host immune system, yet the properties of this organ that confer this ability are not well understood. We are actively working to understand this relationship between the schistosome stem cells and the tegument and are working to discover novel molecules associated with the schistosome tegument. We hope these studies will determine how these parasites evade the host immune system and uncover novel molecules that be exploited as anti-schistosome vaccine candidates.

Publications


Protasio AV, van Dongen S, Collins J, Quintais L, Ribeiro DM, Sessler F, Hunt M, Rinaldi G, Collins JJ, Enright AJ, Berriman M. MiR-277/4989 regulate transcriptional landscape during juvenile to adult transition in the parasitic helminth Schistosoma mansoni. PLoS NTDs 11(5):e0005559. [PDF]

Collins J.J. III 2017. Platyhelminthes. Current Biology 27(7):R252-R256 [PDF]

Collins J.N., Collins J.J. III 2016. Tissue Degeneration following Loss of Schistosoma mansoni cbp1 Is Associated with Increased Stem Cell Proliferation and Parasite Death in vivo. PLoS Pathogens 12(11):e1005963. [PDF]

Collins J.N., Collins J.J. III 2017. Methods for Studying the Germline of the Human Parasite Schistosoma mansoni. Methods Mol Biol. 1463:35-47. [PDF]

Wendt, G.W., Collins J.J. III 2016. Schistosomiasis as a disease of stem cells. Curr Opin Genet Dev.1463:35-47. [PDF]

Collins, J.J., III, Wendt, G.W., Iyer, H.I., Newmark, P.A. 2016. Stem cell progeny contribute to the schistosome host-parasite interface. eLIFE 5:e12473. [PDF]

• Associated “Insight”: Pearson MS, Loukas A. 2016. Stem cells: The parasite’s new clothes. eLIFE 5:e15957.

• Jim rappin' with Chris Smith for the eLife podcast


Wang, J, Collins, J.J. III. 2016. Identification of new markers for the Schistosoma mansoni vitelline lineage. Int J Parasitol.46(7):405-10. [PDF]


Lambrus, B.G., Cochet-Escartin, O, Gao, J, Newmark. P.A., Collins, E.M., Collins, J.J., III. 2015. Tryptophan hydroxylase Is Required for Eye Melanogenesis in the Planarian Schmidtea mediterranea. PLoS One. 2015 May 27;10(5):e0127074. [PDF]


Tharp, M. , Collins, J.J., III, Newmark, P.A. 2014. A lophotrochozoan-specific nuclear hormone receptor is required for reproductive system development in the planarian. Developmental Biology. 396(1):150-7. [PDF]


Collins, J.J., III, and Newmark, P.A. 2013. It's no fluke: Planarians as a model to understand schistosomes.  PLoS Pathogens 9(7): e1003396. [PDF]


Collins, J.J., III, Wang, B., Lambrus, B.G., Tharp, M., Iyer, H., Newmark, P.A. 2013. Adult somatic stem cells in the human parasite Schistosoma mansoni.. Nature 494(7438):476-9. [PDF]

• Associated News and Views: Pearce, E.J., 2013. Parasitology: Rejuvenation through stem cells. Nature 494(7438):438-9.

• Featured on Carl Zimmer's Blog Phenomena: THE LOOM


Wang, B., Collins, J.J., III, and Newmark, P.A.  2013.  Functional genomic characterization of neoblast-like stem cells in larval Schistosoma mansoni.eLIFE 2:e00768. [PDF]

• Associated “Insight”:  Sánchez Alvarado, A. 2013. Parasitism: On the trail of a tropical disease. eLIFE 2:e00768.


Chong, T., Collins, J.J., III, Brubacher J.L., Zarkower D, Newmark, P.A., 2013. A sex-specific transcription factor controls male identity in a simultaneous hermaphrodite. Nature Communications 4:1814. [PDF]


Collins, J.J., III*, King, R.S.*, Cogswell, A., Williams, D.L., Newmark, P.A. 2011. An atlas for Schistosoma mansoni. organs and life-cycle stages using cell type-specific markers and confocal microscopy. PLoS Negl Trop Dis. 5: e1009. [PDF]


Cogswell, A.A., Collins, J.J., III, Newmark, P.A., Williams, D.L. 2011. Whole mount in situ hybridization methodology for Schistosoma mansoni. Mol Biochem Parasitol. 178: 46-50. [PDF]


Collins, J. J., III, Hou, X., Romanova, E. V., Lambrus, B.G., Miller, C. M., Saberi, A., Sweedler, J.V., Newmark, P. A., 2010. Genome-Wide Analyses Reveal a Role for Peptide Hormones in Planarian Germline Development. PLoS Biology 8: e1000509. [PDF]

Protocols


Here are some of the commonly used protocols used in the Collins Lab to study schistosomes.

Contact Us


The Collins Lab is located in the Department of Pharmacology the University of Texas Southwestern Medical Center. We have numerous training opportunities at the graduate and postdoctorate level. If you have any questions, or if you are interested in discussing a position in our lab, please contact us.