Human parasite’s daily rhythms could be targeted for better treatments – Innovita Research

Human parasite’s daily rhythms could be targeted for better treatments

The parasitic worm that causes the neglected tropical disease, schistosomiasis, has daily rhythms in gene expression, including genes that could be targeted in drug development.

For the first time, the worm that causes schistosomiasis has been shown to have a daily rhythm that impacts which genes are switched on at different times.

The new research, from the Wellcome Sanger Institute and collaborators, identified certain genes that are switched on in the parasite to align with the mouse host’s daily rhythms. This gives novel insights into how these centimetre long worms can survive the 24-hour cycles of the immune and blood-clotting systems in the human blood vessels for over 30 years1.

Image credit: Rawlinson et al.

The study, published in BMC Biology, highlights that many genes that could be targeted in the development of treatments and vaccines for schistosomiasis have 24-hour patterns of expression. It suggests that there are certain times of the 24 hour period where these treatments could be more effective, when aligned with peak gene activity in the worm.

Schistosomiasis is a neglected tropical disease caused by the eggs of the female parasitic worm, Schistosoma mansoni. This disease has a vast human impact, causing an estimated 140,000 cases and 11,500 deaths in 2019 alone2. It is prevalent across sub-Saharan Africa, certain South American countries and the Caribbean, with some reports in the Arabian Peninsula3. Despite the profound global impact of schistosomiasis, there is complete reliance on a single drug for treatment, and new evidence suggests that there is growing drug resistance in some worm populations4,5. Therefore, there is a need to develop a new generation of therapeutics.

The cycle of day and night, imposed by the Earth turning on its axis, is one of the most striking features of the world in which we live. To align with this, many species exhibit daily changes in their behaviour and/or physiology. The synchrony of an organism with the environment is critical to its survival, and a mismatch in this can lead to the organism being unable to survive.

Disease-causing single celled parasites, such as Plasmodium parasites that live in mosquitoes and humans and cause malaria, have been proven to have daily rhythms in gene expression and these have been shown to impact drug sensitivity6-8. However, it has never been studied in a multi-celled parasite like Schistosoma mansoni before.

In this new study, researchers collected worm samples from three infected mice every four hours over a 44 to 48 hour period. The gene expression of the worms was analysed over the time course and 209 genes were revealed to have 24-hour patterns of abundance. The function of these genes suggest that when the host is active the parasite is stressed, switching on genes that help protect the parasite from the rise of the host’s body temperature. Comparatively, during the host’s resting phase the parasite interacts with the host’s immune and blood coagulating systems and experiences a rush in activity of genes involved in changing food into energy.

This study also found that many genes expressed in the female reproductive system and involved in egg laying have daily rhythms of expression, and these translated to daily patterns of egg laying. Some of these genes could be targeted to provide new therapies to help treat schistosomiasis.

Tracking when these genes are switched on, and the mechanisms behind this, could be utilised to ensure that the treatments or vaccines are given when the gene is most active to ensure optimum effectiveness of treatments.

More information

  1. Harris AR, Russell RJ, Charters AD. (1984) A review of schistosomiasis in immigrants in Western Australia, demonstrating the unusual longevity of Schistosoma mansoni. Trans R Soc Trop Med Hyg. 78(3):385-8.
  2. Global Burden of Disease Study 2019 (GBD 2019). Results [Global Burden of Disease Collaborative Network] Institute for Health Metrics and Evaluation (IHME).
  3. Schistosomiasis. DPDx – Laboratory Identification of Parasites of Public Health Concern. Centre for Disease Control and Prevention (CDC). Available [Accessed November 2021]
  4. Ismail M, Metwally A, Farghaly A, Bruce J, Tao LF, Bennett JL. (1996) Characterization of isolates of Schistosoma mansoni from Egyptian villagers that tolerate high doses of praziquantel. American Journal of Tropical Medicine and Hygiene.;55:214–218.
  5. Crellen T, Walker M, Lamberton PH, Kabatereine NB, Tukahebwa EM, Cotton JA, Webster JP. (2016) Reduced efficacy of praziquantel against Schistosoma mansoni is associated with multiple rounds of mass drug administration. Clin Infect Dis. 63(9):1151-1159.
  6. Rijo-Ferreira F, Pinto-Neves D, Barbosa-Morais NL, Takahashi JS, Figueiredo LM. (2017) Trypanosoma brucei metabolism is under circadian control. Nat. Microbiol. 2,17032.
  7. Rijo-Ferreira F, Acosta-Rodriguez VA, Abel JH, Kornblum I, Bento I, Kilaru G, Klerman EB, Mota MM, Takahashi JS. (2020) The malaria parasite has an intrinsic clock. Science.368,746-753.
  8. Smith LM, Motta FC, Chopra G, Moch JK, Nerem RR, Cummins B, Roche KE, Kelliher CM, Leman AR, Harer J, Gedeon T, Waters NC, Haase SB.(2020) An intrinsic oscillator drives the blood stage cycle of the malaria parasite Plasmodium falciparum. Science. 754-759.

Source: Sanger Institute