Eric Schwegler – Neglected Tropical Diseases

A medical Negligence results in devastating Consequences

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 of the world.[1] NTDs threaten the health of both humans and their livestock,[2] whereby vast areas of infested countries are rendered uninhabitable. Limited access to adequate health services complicates surveillance and therefore diagnosis and treatment of an infection.[3] The lack of financial resources, inadequate sanitation and population displacements e.g. due to military conflicts are further important factors that facilitate NTD transmission in endemic countries.[1] [4]

Taking a closer look on the temporality of NTDs, one observes an entanglement between NTD epidemics and the socio-economic situation of a country. One historic example is the murderous Rubber Harvest of the so called “Congo Free State”, ordered by its usurpator Leopold II, King of Belgium in the late 19th century.[5] A growing demand for rubber dramatically increased the value for latex, a milky juice produced by certain plants. Due to the greed of Leopold II, thousands of Congolese people were forced to harvest vines containing the valuable resource in Trypanosoma-infested areas.[5] [6] The continuous exposure of the Congolese to Trypanosoma-infected flies thus led to a singular outbreak of African Sleeping Sickness in the Congo Basin.[5] This example hauntingly demonstrates how the economic interests of a few can lead to the death of millions via NTDs.

Temporality of NTDs is a major part of my studies because the entanglement of colonial economy with NTDs can be applied to nowadays epidemics in a globalised world.[3] Knowledge of these relationships may provide suitable lessons to prevent future outbreaks of NTDs. Additionally, a closer look on politics and social structures of an infested country may contribute to a better understanding of the origin of NTDs and their impact on every day life. Thus, an interdisciplinary community like the Graduate College “Life Sciences – Life Writing” provides an ideal conceptual framework to conduct research on this topic.

Infections with parasites rank among the most prevalent and deadly NTDs.[3] They are caused by e.g. members of the Trypanosomatida parasite family, namely various Trypanosoma and Leishmania species.[1-3] Diseases caused by Trypanosomatida are found worldwide and are transmitted to a human or animal (host) via the bite of an infected insect (vector).[1] [2] The most prominent diseases caused by Trypanosomatida are the African Sleeping Sickness, the Chagas Disease, Leishmaniasis and numerous plagues limiting stock breeding, namely Nagana, Surra and several others.[2] [3]

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

As a Biomedical Chemist, I am dedicated to understanding Chemistry of Life in various organisms. During my PhD studies, I thus will focus on an essential metabolic pathway of Trypanosomatida as a new therapeutic target. This pathway, namely the Peroxide Clearance Cascade, protects Trypanosomatida 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] Since the parasitic cascade strongly differs from the human analog and was shown to be essential for Trypanosomatida, it is reported to be an ideal drug target.[7]

The Peroxide Clearance Cascade (PCC) consists of various components: Enzymatically active proteins and small molecules.[7] They can be thought of as gears: Impairing one results in the arrest of the whole system. In case of the PCC, this arrest causes an accumulation of ROS within Trypanosomatida and ultimately death of these parasites.[7] For this reason, research on the PCC components and their interaction with each other is the main focus of my biochemical studies.

Author: Eric Schwegler

 

References

[1] https://www.who.int/neglected_diseases/ (accessed Mai 1st, 2020)

[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] Lyons M. The Colonial Disease: A Social History of Sleeping Sickness in Northern Zaire, 1900-1940. Cambridge: Cambridge University Press; 1992.

[6] Casement R. Correspondence and Report from His Majesty's Consul at Boma Respecting the Administration of the Independent State of the Congo. 1903.

[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