Eric Schwegler – Neglected Tropical Diseases

Interdisciplinary and Biochemical Studies on Kinetoplastid Diseases

The WHO defines Neglected Tropical Diseases (NTDs) as “a diverse group of communicable diseases that prevail in tropical and subtropical conditions in 149 countries.”[1] In sum, they affect over a billion people in the poorest countries in the world. Infections with kinetoplastid parasites, namely Trypanosoma and Leishmania, rank among the most deadly NTDs.[1-3] Kinetoplastid parasites are being transmitted to a human or animal (host) via the bite of an infected insect (vector).[1] [2] Human infections with Kinetoplastida are called either African Sleeping Sickness, Chagas Disease or Leishmaniasis depending on the parasite species. Animal infections are known as plagues limiting stock breeding.[2] [3]

In my PhD thesis, I intend to develop an interdisciplinary description of kinetoplastid diseases. My studies are intended as a tool for creating patient-centered therapies and effective counter-measures to prevent disease transmission. During my studies, I will confine myself to the basics of multiple disciplines in order to highlight potential interdisciplinary exchanges in detail.

A closer look on kinetoplastid diseases sheds light on the complexity of this topic. At first glance, humans, animals and insects are involved in disease transmission. Consequently, knowledge from multiple natural scientific disciplines, e.g. human and veterinary medicine, biology, entomology, and ecology, are required for a basic description of the diseases. Considering all these perspectives in a study is known as the “One Health” approach.[5]

Nonetheless, natural sciences alone can neither explain the exceptionally high incidences of kinetoplastid diseases in so called “failed states” nor the neglect by wealthy countries. Income, government stability, infrastructure, civil unrest, and public awareness are just a few aspects which make an impact on kinetoplastid disease transmission and neglect.[1] Therefore, I will employ contemporary and historical studies on society in order to create epidemiological knowledge for robust counter-measures.

Beyond the mere description of kinetoplastid diseases, I intend to focus on the patient’s situation. A central aspect of my research is social stigma which is a disease burden beyond the biomedical perspective.[6] I am interested in the actual impact of social stigma on the patient’s life and whether stigma is sufficiently considered in therapies.

Medication for some kinetoplastid diseases exists but is expensive, barely accessible, hard to administer and highly toxic itself.[2] [3] It is therefore most unfortunate that progress in the development of anti-parasitic drugs has been negligible in the last 50 years.[3] For this reason, the development of new therapeutic approaches for kinetoplastid diseases is my second main research interest.

In my biochemical studies, I will focus on the unique parasitic redox metabolism of human pathogenic Kinetoplastida. The so called “Peroxide Clearance Cascade” protects Kinetoplastida from oxidative damage caused by the accumulation of reactive oxygen species (ROS).[7] ROS are small molecules, created in every organism as a side product of nutrient digestion and need to get degraded to maintain cell viability.[8] The parasitic cascade strongly differs from the human analogue and was shown to be essential for Kinetoplastida. For this reason, proteins involved in parasitic ROS detoxification, such as my main research interest Tryparedoxin, are regarded as promising drug targets.[7]

Author:
Eric Schwegler
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References

[1] https://www.who.int/neglected_diseases/ (Accessed 01.05.20)

[2] Varikuti S et al. Host-Directed Drug Therapies for Neglected Tropical Diseases Caused by Protozoan Parasites. Front Microbiol. 2018; 9:2655. doi:10.3389/fmicb.2018.02655

[3] Hotez PJ et al. Control of Neglected Tropical Diseases. N. Engl. J. Med. 2007; 357:1018. doi: 10.1056/NEJMra064142

[4] Büscher P et al. Human African Trypanosomiasis. Lancet 2017; 390:2397.

[5] Taking a Multisectoral, One Health Approach: A Tripartite Guide to Addressing Zoonotic Diseases in Countries (pp.1–9). www.who.int/initiatives/tripartite-zoonosis-guide (Accessed 16.01.21)

[6] Bilgic-Temel A et al. Cutaneous leishmaniasis: A neglected disfiguring disease for women. Int. J. W. Dermatol. 2019; 5 (3). doi: 10.1016/j.ijwd.2019.01.002.

[7] Jaeger T et al. The thiol-based redox networks of pathogens: Unexploited targets in the search for new drugs. Biofactors. 2006; 27(1-4):109. doi: 10.1002/biof.5520270110

[8] Ray PD et al. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal. 2012; 24(5):981. doi:10.1016/j.cellsig.2012.01.008