Aaron Logsdon



BBB, Blood brain barrier; DDT, dichlorodiphenyltrichloroethane; DRC, the Democratic Republic of the Congo; HAT, Human African Trypanosomiasis; NECT, nifurtimox-eflornithine combination therapy; NTD, neglected tropical disease; ODC, ornithine decarboxylase; VSG, variant surface glycoprotein



antigen, antigenic variation, arsenic, asymptomatic, clinical trial, dementia, drug, drug resistance, energy metabolism, endemic, epidemic, fever, host, hypoglycemia, immune cell, immune response, infection, inhibitor, insecticide, macrophage, neglected tropical disease, neuron, parasite, plasma cell, polyamine, protein, rational drug design, screening, T cell, vaccine, vector

A message from the author

Recently, I had the opportunity to research a disease called Human African Trypanosomiasis (HAT) for my final year laboratory project at Imperial College London. I discovered that even though millions of people are currently at risk of contracting HAT, modern medicine has largely neglected this disease. This is mainly because HAT predominantly affects people in the most impoverished regions of Africa. One of Personalize My Medicine´s goals is to make more people aware of neglected diseases with unmet treatment goals, such as HAT. Here I present to you the story of HAT, focusing on how the treatment of this disease has developed from the past to the present and discussing the hurdles that still need to be overcome.


1. Introduction to HAT

1.1. HAT is a neglected tropical disease

Neglected tropical diseases (NTD) are a diverse group of 20 conditions prevalent in tropical regions, affecting over one billion people. HAT is a member of the NTD group and is endemic (continually present) in 36 African countries (Franco et al., 2022; Simarro et al., 2010). HAT is almost always deadly if left untreated, and due to limited treatment options, 55 million people in endemic countries are at risk of dying from this disease. (Franco et al., 2022; Kennedy, 2013). The risk of an epidemic (large disease outbreaks) occurring in affected regions remains high (Franco et al., 2014). Recently, there have been renewed efforts to develop effective treatments for HAT. However, the disease requires increased global attention to ensure that more effective treatments are developed and available to affected and at-risk populations.

1.2. Trypanosoma brucei causes HAT

Trypanosoma brucei is a unicellular (single cell) parasite that is the causative agent of HAT. There are two subspecies of T. brucei that can cause HAT, and these are T. brucei gambiense and T. brucei rhodesiense (Büscher et al., 2017). T. brucei infects the tsetse fly, which feeds on the blood of humans (Büscher et al., 2017). When an infected tsetse fly bites a person, T. brucei is injected into the bloodstream (Figure 1). Here, the parasite multiplies, leading to the symptoms of HAT, which include recurring fever and dementia, which are discussed further in section 1.3. (Büscher et al., 2017). The cycle of infection is repeated when another tsetse fly bites the infected person, as in the process the T. brucei parasite is transmitted to this fly’s gut (Figure 1) (Büscher et al., 2017). In T. brucei infection, the tsetse fly is known as the vector, which transmits the parasite between the fly and human, while the human is known as the host as the disease only occurs in the human (Figure 1).

Figure 1. Trypanosoma brucei transmission cycle

In the image above, the blue panel represents the T. brucei vector, with the human host shown in black. The red panel represents the T. brucei vector, with the tsetse fly shown in black. T. brucei is represented by the grey cell shown in each panel.


1.3. HAT disease stages

There are two different stages of HAT disease. During the early stage of HAT, the T. brucei parasite spreads to various tissues and organs via the host’s bloodstream (Büscher et al., 2017). The host´s immune system mounts a strong response to eliminate the parasite on encountering the parasite. This immune response involves recruiting different types of immune cells to specific sites in the body. Plasma cells produce proteins called antibodies that recognize and bind T. brucei (Figure 2) (Magez et al., 2008). A different type of immune cell called a macrophage can bind to the antibody bound to T. brucei, engulfing the entire complex, thereby killing the parasite (Figure 2) (Onyilagha & Uzonna, 2019). During this immune response, the body sends signals to the brain that trigger it to raise the core body temperature. This rise in body temperature allows immune cells to act more quickly (Dinarello, 2004). This increase in core body temperature leads to a recurring fever in HAT patients during the early stage of the disease (Dinarello, 2004; Mpandzou et al., 2011). In the late stage of HAT, T. brucei cells that evade elimination cross the blood brain barrier (BBB) (Figure 2). The BBB is a layer of cells between the blood and the brain with very tight junctions between the cells it comprises (Figure 2) (Mulenga et al., 2001). The parasite disrupts the BBB, allowing immune cells, including T cells, to enter the brain (Figure 2). The T cells can damage and kill brain cells (neurons), which can lead to conditions such as dementia (Figure 2) (Blum et al., 2006; Frevert et al., 2012; Laperchia et al., 2016).



Figure 2. Overview of T. brucei infection

In the image above, the light red panel represents the blood while the light blue panel represents the brain. The two colored panels are separated by two layers of cells, the BBB. A key can be found below the panels. The image shows that T. brucei may be found in the blood and/or the brain during different stages of infection. The parasite is only found in the brain during the later stage of HAT. When T. brucei is present in the blood, it can be bound by antibodies that are recognized and destroyed by macrophages. The figure shows a macrophage beginning to engulf a T. brucei-antibody complex. T. brucei cells that are not intercepted and destroyed may cross the BBB in the later stage of HAT. This allows immune cells in the blood, such as T cells, to cross the BBB, damaging brain cells (neurons).


1.4. Challenges to developing treatments for HAT

There are several challenges when it comes to developing HAT treatment. First, different treatments are more effective for infections caused by T. b gambiense infection than infections caused by T. b. rhodesiense infection (Steverding, 2010). The further challenge is that the treatment for early-stage HAT, such as suramin and pentamidine, is rarely effective for treating late-stage HAT, as most drugs cannot get across the BBB (Steverding, 2010). In addition, late-stage treatment, such as melarsoprol, is often toxic, so doctors try to avoid using it to treat early-stage HAT (Steverding, 2010). Finally, many of the treatment schedules for HAT are complex and require the patient’s hospitalization. All of these challenges mean that it can be difficult to treat patients living in rural areas who may have little access to healthcare or may only have access to hospitals that lack modern medical equipment (Jacobs et al., 2011). Currently available treatments for HAT are discussed in sections 2., 3. & 4.

The development of a HAT vaccine would massively simplify the problem of HAT treatment. However, to date, a vaccine has not been possible, and likely never will be, due to a mechanism known as antigenic variation (La Greca & Magez, 2011). Vaccines cause plasma cells to produce antibodies, which recognize the organism being vaccinated against, as discussed in section 1.2. (La Greca & Magez, 2011; Magez et al., 2008). The antibodies recognize specific parts of the organism called antigens, such as surface proteins, called variant surface glycoprotein (VSG) in the case of T. brucei (Figure 3) (La Greca & Magez, 2011). However, T. brucei cells can change the VSG protein covering its surface with an antigenically distinct VSG, which means the now old antibody does not recognize the new VSG protein (Figure 3). Antigenic variation in T. brucei cells is essentially random, and most will not undergo antigenic variation before antibody-based detection, and elimination occur, but the few that do escape immune detection and multiply, meaning all surviving T. brucei cells are not recognized by the old antibody (La Greca & Magez, 2011). T. brucei cells contain ~ 2000 types of VSG, meaning the above escape process could occur continuously, making a HAT vaccine not feasible (Cross et al., 2014; La Greca & Magez, 2011).


Figure 3. Overview of T. brucei infection

The above image is divided into a blue panel and a red panel, with a key beneath. The blue panel shows a zoomed-in image of the T. brucei cell surface with a hypothetical VSG, (VSG X) attached to the surface. A hypothetical antibody (Antibody Z) is produced against VSG X, to which Antibody Z recognizes and binds, leading to destruction of the T. brucei cell. The red panel shows a zoomed-in image of the same T. brucei cell surface, which has undergone antigenic variation, switching VSG X for another hypothetical VSG, VSG Y. As Antibody Z cannot recognize VSG Y, it is unable to bind and the T. brucei cell evades elimination.


2. The modern history of HAT  

2.1. 1896-1906 epidemic

Millions of people died from HAT during the 20th century (Büscher et al., 2017). This was predominantly due to the colonization of African nations during the late 19th century, such as in the Congo Free State, now the DRC (Lyons, 1992). Belgium colonized the Congo Free State in the late 19th century brutally, displacing millions of people who went on to experience famine (Lyons, 1992). This led to many people occupying poor living conditions with poor hygiene, allowing T. brucei to be easily transmitted between people (Lyons, 1992). Very little was done to change these circumstances during the resulting epidemic, which killed 300,000 and 500,000 people in the Congo Basin and the Busoga Focus in Uganda and Kenya, respectively (Steverding, 2010).

2.2. 1920s epidemic: Advancements in disease control

A further epidemic that took place in Africa in the 1920s was successfully controlled by developing drugs to treat HAT and carrying out both case screening and vector control. Efforts to develop treatments for HAT began in the 1910s, resulting in the development of tryparsamide in 1921 and Suramin in 1922. Suramin effectively treated early-stage HAT caused by T. b. rhodesiense (Section 3.1.). Tryparsamide was able to cross the BBB and demonstrate success in treating late-stage HAT (Steverding, 2010). In 1940, pentamidine was introduced and showed success in treating early-stage HAT caused by T. b. gambiense (Section 3.1.). Then, in 1949, melarsoprol was introduced as the first drug found to be effective for the treatment of late-stage T. b. rhodesiense infection (Section 3.2.) (Steverding, 2010).

During the 1920s, colonial powers such as the French in Cameroon introduced mobile teams carrying out screenings of millions of at-risk people to diagnose HAT cases and reduce the pool of asymptomatic people to lower disease transmission (Lyons, 1992). Vector control, the control of tsetse fly numbers and distribution, began in 1910, and in 1949, the insecticide dichlorodiphenyltrichloroethane (DDT) was introduced. DDT effectively killed the tsetse fly and reduced disease transmission in regions where HAT was endemic (Vanderplank, 1947). Drug development and the reduction of disease transmission meant that HAT began to fall out of significance by the mid-1960s, with less than 5000 cases reported in the continent of Africa at this point (World Health Organisation, 2000).

2.3. 1970 to 1990s epidemic: A decline in disease control

By the 1960s, most African countries affected by HAT became independent of their colonial powers, leading to a period of political instability, which had a disastrous knock-on effect on local health services. This problem was compounded by a reduction in case screening due to decreasing cases in affected countries, which led to an increase in asymptomatic people (World Health Organisation, 2000). Further, due to concerns about the effect of DDT on the environment, a worldwide ban was placed on the insecticide’s use in disease vector control in the 1970s, leading to increased tsetse fly numbers (World Health Organisation, 2000). The above issues were compounded by a lack of drug development in this period, which ultimately led to a steady increase in HAT cases, which in turn led to another large HAT epidemic that affected Angola, Congo, Southern Sudan, and the West Nile district of Uganda (World Health Organisation, 2000). The epidemic continued into the 1990s when eflornithine was first introduced to treat late-stage HAT caused by T. b. gambiense (Section 3.2.) (Eperon et al., 2014). Although the administration regime of the drug was harsh, the drug was considered to be a welcome alternative to the more toxic and less successful treatment at the time, such as melarsoprol (Balasegaram et al., 2006).

2.4. Twenty-first century stability: Lessons for prolonged disease control

Due to improvements in HAT treatment and post-epidemic case surveillance, fewer cases of HAT are reported each year, with only 992 and 663 reported cases globally in 2019 and 2020, respectively (Franco et al., 2022). However, only 2.8 million and 1.6 million of the 55 million people at risk were screened in 2019 and 2020, respectively, meaning that the actual case number could be significantly higher (Franco et al., 2022). This lack of case screening is concerning, considering this very factor contributed to causing the previous epidemic. Even more concerning is the lack of universal treatment accessible for all HAT patients, as if addressed, future epidemics could be avoided entirely, as discussed in sections 3. and 4. The modern history of HAT is summarized in the below timeline (Figure 4).

Figure 4. A timeline summarising the modern history of HAT

The above timeline consists of several colour-coded periods, each supplemented by the critical moment of that period. The timeline is divided into three sections based on the three HAT epidemics of the 20th century.

Figure 4. A timeline summarizing the modern history of HAT

The above timeline consists of several color-coded periods, each highlighting a critical moment of that period. The timeline is divided into three sections based on the three HAT epidemics of the 20th century


3. Modern-day HAT treatment

3.1. Drugs for treating early-stage HAT

At present, Suramin remains the treatment of choice for treating T. b. rhodesiense infection in early-stage HAT (Barret et al., 2009). While, the drug´s mechanism of action remains unknown, no resistance to suramin has been reported in the field, and it is thought that the drug likely acts upon multiple targets within T. brucei, which makes it more difficult for the parasite to evolve mechanisms to evade its action (Barret et al., 2009). Suramin cannot cross the BBB and therefore is not effective in treating late-stage HAT (Barret et al., 2009). Significant side effects of suramin that are commonly reported include nerve damage and renal toxicity (Barret et al., 2009). Suramin is effective in treating T. b. gambiense infection. However, the treatment schedule is very complex compared to that of pentamidine (Barret et al., 2009. Therefore, suramin is not used to treat T. b. gambiense infection. The drug´s main characteristics are summarized in Table 1.

For T. b. rhodesiense infection, suramin is still the treatment of choice for early-stage HAT (Barret et al., 2009). Suramin’s mechanism of action remains unknown. No resistance to suramin in the field has been reported meaning the drug likely acts upon multiple targets in T. brucei, making it harder for the parasite to evolve mechanisms around suramin’s activity (Barret et al., 2009). Suramin cannot cross the BBB and therefore is ineffective in treating late-stage HAT (Barret et al., 2009). Side effects of suramin are commonly reported, including nerve damage (Barret et al., 2009). Suramin does show effectiveness in treating T. b. gambiense infection but has a highly complex treatment schedule compared to another discussed drug, pentamidine, and therefore is not utilised for this (Barret et al., 2009). Suramin has been summarised below (Table 1).

Until 2019, pentamidine was the treatment of choice for early-stage HAT caused by T. b. gambiense infection, but it is still worth discussing. Pentamidine has reduced activity against T. b. rhodesiense infection, not putting suramin out of business (Barret et al., 2009). Again, the mechanism of action by pentamidine is unclear. Resistance against pentamidine has been reported but does not occur readily as pentamidine uses multiple mechanisms to enter and damage T. brucei, which is beyond the scope of this article (de Koning, 2008). Pentamidine does not seem to cross the BBB in significant concentrations, explaining its lack of effectiveness in treating late-stage HAT (Sanderson et al., 2009). Pentamidine causes severe toxicity in at least half of receiving patients, including life-threatening hypoglycaemia (low blood sugar) (Barret et al., 2009). Due to this, pentamidine was recently succeeded by the relatively non-toxic fexinidazole, which is discussed later on (Section 3.3.). Pentamidine has been summarised below (Table 1).





First Year of Use





Disease Stage


Mechanism of Action


Common Major Side Effects



in T. brucei



Mode of Administration









T. b. rhodesiense








Renal toxicity and nerve damage





Intravenous injection









T. b. gambiense














Intramuscular injection


Table 1. A summary of the use of suramin and pentamidine in HAT treatment


3.2. Drugs for treating late-stage HAT

Melarsoprol is the treatment of choice for T. b. rhodesiense infection in late-stage HAT as no other treatment options are effective. Melarsoprol is based on arsenic, a highly toxic element that has been implicated in approximately 5.9% of treatment-related deaths (Schmid et al., 2005). Due to this toxicity, melarsoprol is reserved for late-stage HAT treatment (Schmid et al., 2005). While the mechanism of action of melarsoprol is not understood, melarsoprol is thought to act upon not only numerous targets within T. brucei cells, but also many targets within the cells of the human host, leading to the reported toxicity in patients (Barret et al., 2009). Resistance to melarsoprol has been reported (de Koning, 2008; Robays et al., 2008). While Melarsoprol has shown to be effective for treating T. b. gambiense infection in late-stage HAT, the less toxic eflornithine is also available for T. b. gambiense infection (Barret et al., 2009). Melarsoprol has been summarized below (Table 2).

Unlike all of the other drugs used previously for the treatment of HAT, Eflornithine has a known mechanism of action. Eflornithine prevents a protein called ornithine decarboxylase (ODC) from functioning (Barret et al., 2009). ODC is required for T. brucei cells to produce polyamines, a type of molecule that is essential for cell growth (Pegg & Feith, 2007). Eflornithine reacts with ODC, thereby altering ODC’s structure, which in turn disrupts the function of ODC, preventing polyamine production and cell growth, and ultimately resulting in the death of T. brucei cells (Barret et al., 2009). Eflornithine is known to be effective for the treatment of T. b. gambiense infection in late-stage HAT as it is able to cross the BBB and causes relatively few toxicities compared to melarsoprol (Balasegaram et al., 2009). As of 2009, eflornithine has been used in nifurtimox-eflornithine combination therapy (NECT) as the treatment of choice for T. b. gambiense infection in severe late-stage HAT. Nifurtimox can generate free radicals inside T. brucei cells. Free radicals are a type of molecule that is highly reactive and that can damage DNA and proteins (Jacobs et al., 2011). Treatment with NECT has a 96.5% cure rate compared to a 91.6% cure rate when administering eflornithine alone (Priotto et al., 2009). Resistance to NECT is unlikely as it would require the T. brucei parasite to acquire mutations that allow it to evade the effects of both drugs. The main characteristics of NECT are summarized in Table 2.



First Year of Use





Disease Stage


Mechanism of Action


Common Major Side Effects



in T. brucei



Mode of Administration












T. b. rhodesiense












Brain damage








Intravenous injection












T. b. gambiense




Late (severe)


Growth inhibition and DNA/protein damage














Intravenous injection

Table 2. A summary of the use of melarsoprol and NECT in HAT treatment

The above table describes the use of melarsoprol and NECT in HAT treatment, as well as the mechanism of action and common major side effects of each drug. The level of resistance that T. brucei shows towards each drug and the mode of delivery are also indicated.


3.3. Recent advancements in HAT treatment

As many HAT patients live in remote regions of Africa, it was difficult for them to access treatment as all treatments mentioned so far involve the injection of a drug and requiring the patient to be hospitalized (Jacobs et al., 2011). Therefore, there was much need for a drug that did not require HAT patient hospitalization and could be easily distributed to all regions of Africa. The problem of burdensome treatment was partly solved in 2019 with the release of fexinidazole, a drug that is orally administered as a pill (Deeks, 2019). Fexinidazole is a drug that creates reactive molecules that are indirectly toxic to T. brucei cells, damaging the T. brucei parasite DNA and leading to death (Deeks, 2019). The active molecules produced by fexinidazole can pass through the BBB and cause minimal toxicity. This makes it feasible to use fexinidazole to treat early-stage and late-stage HAT (Deeks, 2019). Clinical trials conducted prior to 2019 showed fexinidazole to be effective when treating patients experiencing both stages of HAT caused by T. b. gambiense infection (Mesu et al., 2018). As fexinidazole is orally administered and NECT is not, fexinidazole became the treatment of choice for early-stage HAT and non-severe late-stage HAT caused by T. b. gambiense infection (Deeks, 2019). However, NECT was found to be more effective when treating severe late-stage patients, and therefore, NECT remains the first choice of treatment for T. b. gambiense infection in late-stage HAT (Mesu et al., 2018). The main characteristics of fexinidazole been are summarized in Table 3.

Fexinidazole is taken as a pill once a day for ten days (Mesu et al., 2018). HAT treatment in remote areas could be simplified further if a single-dose drug was available. Acoziborole, a drug currently in testing, has been shown to kill T. brucei cells by preventing protein production (Dickie et al., 2020). Initial trials have indicated that acoziborole is effective for the treatment of both stages of HAT caused by T. b. gambiense infection, all with a single oral dose. However, the safety of this treatment is yet to be determined (Dickie et al., 2020). The main characteristics of acoziborole are summarized in Table 3. Even with acoziborole on the horizon, no orally administered drug is currently available for T. b. rhodesiense infection. Ideally, a universal HAT treatment needs to be developed to avoid future epidemics.




First Year of Use





Disease Stage


Mechanism of Action


Common Major Side Effects



in T. brucei



Mode of Administration












T. b. gambiense




Early and late (non-severe)



Indirect toxicity through reactive molecule production








Not yet known

















T. b. gambiense





Early and late



Inhibition of protein production




Not yet known




Not yet known




Pill (single dose)

Table 3. A summary of the use of fexinidazole and acoziborole in HAT treatment

The above table describes the use of fexinidazole and acoziborole in HAT treatment, as well as the mechanism of action and common major side effects of each drug. The level of resistance T. brucei shows towards each drug and the mode of delivery are also indicated.


4. The future of HAT treatment

4.1 Ongoing clinical trials

Clinical trials are conducted to determine whether a new treatment is safe and effective and whether it may be safer and as or more effective than the current standard of treatment. The ClinicalTrials.gov website provides information on ongoing clinical trials. Currently, there are two clinical trials being conducted to assess HAT treatments. The aim of the first of these (NCT03974178) is to study the safety and effectiveness of fexinidazole in treating HAT patients with T. b. rhodesiense infection compared to the current gold standard, the highly toxic melarsoprol, in order to determine whether fexinidazole could replace melarsoprol. If fexinidazole is found to be effective, HAT caused by either T. b. rhodesiense infection or T. b. gambiense infection could be treated with an orally administered pill in non-severe cases. The aim of the second clinical trial (NCT05256017) is to study the safety of acoziborole in treating HAT patients with T. b. gambiense infection, in order to determine whether a single dose oral treatment could become the gold standard for all HAT cases caused by T. b. gambiense infection. Both of these clinical trials are currently recruiting individuals. If you or anyone you know may benefit from partaking in either trial, details of both can be found in Table 4.



ClinicalTrials.gov Identifier


Location of Clinical Trial


Contact Information






Rumphi District Hospital, Malawi


Lwala Hospital, Uganda














Hospital of Dipumba, DRC


General Referral Hospital of Masi-Manimba, DRC


General Hospital of Bandundu, DRC


General Referral Hospital of Dubreka, Guinea












Table 4. Clinical trials available on ClinicalTrials.Gov studying HAT treatment

The above table describes the clinical trials currently assessing HAT treatments. The identifier for each clinical trial has been provided, together with the locations of each trial and contact details.


4.2. Rational drug design

Drugs such as fexinidazole and acoziborole represent progress in HAT drug development. Both fexinidazole and acoziborole were identified by testing thousands of potential and/or pre-existing drugs and their effects against T. brucei. This approach significantly increased the chances of identifying effective, non-toxic drugs with an understandable mechanism of action. However, previous empirical approaches to identifying drugs have meant that often the mechanism of action of the drug identified is either poorly understood or is entirely unknown. Improved drug development can be made possible by using the approach of rational drug design which involves three steps (Jacobs et al., 2011). The first step of the process involves identifying a molecule that is relevant to the disease being studied. The second step is to determine the structure and function of the molecule identified. The third and final step is to use information from step two, to design a drug that interacts with the molecule in a therapeutically beneficial way. Therefore, the rational drug design process allows for the mechanism of action to be determined before the drug is made, making the process much more specific (Jacobs et al., 2011).

The first step in rational drug design is to identify a molecule that is relevant to the disease being studied. For HAT, it was necessary to identify a druggable molecule in T. brucei. Target molecules include those involved in T. brucei energy metabolism, an area that has been well-researched. (Verlinde et al., 2001). Energy metabolism is the process by which an organism generates energy from nutrients consumed and digested. Most of the proteins involved in T. brucei energy metabolism are well-studied and there is high degree of similarity between these proteins in T. b. gambiense and T. b. rhodesiense. This means that a drug could potentially be designed to target and disrupt a protein to give therapeutically desirable effects in both T. b. gambiense infection and T. b. rhodesiense infection (Verlinde et al., 2001). However, as all living organisms carry out energy metabolism, human cells contain energy metabolism proteins similar to those of T. brucei, but with minor differences. The process of rational drug design involves taking into account those differences in the design of a drug in such as way that only the T. brucei energy metabolism proteins are targeted (Figure 5). The aim is to design a drug that will only disrupt energy metabolism in T. brucei cells, leading to the death of T. brucei cells, while not causing any harm to the patient’s cells (Figure 5). Furthermore, as the rational drug design approach allows for complete control of a drug’s properties, a drug could efficiently be designed to cross the BBB. Therefore, rational drug design could make it possible to create a universal drug that could be easily administered to all HAT patients.



Figure 5. A theoretical example of how rational drug design works

In the above image, the blue panel represents T. brucei, and the red panel represents the human. Each panel contains a hypothetical protein, Protein X. Protein X is the same in T. brucei and humans, apart from a difference represented by a triangle in T. brucei and by a circle in humans. A hypothetical drug, called Drug Y, has been designed to exploit this difference. Drug Y has been designed with a triangle shape groove complementary to the triangle extension of Protein X in T. brucei, allowing Drug Y to bind and interfere with the protein. However, the triangle shape groove of Drug Y is not complementary to the circle extension of Protein X in humans and, therefore, cannot bind and interfere with the human version of the protein, thereby avoiding toxic effects in humans.


5. Conclusion

HAT is an NTD that has long been neglected by modern medicine. Several deadly HAT epidemics in the 20th century highlighted the need for continuous vector control, case screening, and, most importantly, the development of effective solutions to prevent future epidemics. Historically, the treatment of HAT has been complicated by the so-far insurmountable challenges to vaccine development for HATand the need for different drugs to separately treat T. b. rhodesiense infection and T. b. gambiense infection, as well as different treatment for the early stage and late stage of HAT. The treatment problem has been further complicated by the fact that most patients live in remote locations in Africa, making it difficult for them to access treatment and adequate health services. Medical development originally produced drugs such as suramin and tryparsamide, which are crude, relatively ineffective, highly toxic, and difficult to administer. However, recent advancements in the approach towards drug design have produced drugs such as fexinidazole, which have greater specificity and are non-toxic and can be more easily administered. Previous approaches to drug design have not been successful in developing a universal drug that is effective for the treatment of all HAT cases. Rational drug design focusing on essential and well-studied processes in T. brucei, such as energy metabolism may lead to greater success. The development of an easily administered and non-toxic universal drug is needed to finally make HAT epidemics a thing of the past.


Useful links

https://www.youtube.com/watch?v=qNWWrDBRBqk&ab_channel=Kurzgesagt%E2%80%93InaNutshell – Video to NTDs.

https://www.who.int/news-room/fact-sheets/detail/trypanosomiasis-human-african-(sleeping-sickness) – World Health Organisation page on HAT.

https://www.youtube.com/watch?v=mKnlRVfjl-o&ab_channel=Let%27sLearnAboutBugs – Introductory video to HAT.

https://www.youtube.com/watch?v=NgWWCPSxw0c&ab_channel=DrugsforNeglectedDiseasesinitiative – Video on the history of HAT.

https://www.youtube.com/watch?v=NgWWCPSxw0c&ab_channel=DrugsforNeglectedDiseasesinitiative – Video on treatment for HAT (skip to 12:55).

https://www.youtube.com/watch?v=PLrmdrhziDc&ab_channel=DrugsforNeglectedDiseasesinitiative – Video on NECT.

https://dndi.org/research-development/portfolio/fexinidazole/ – Video on Fexinidazole.

https://www.youtube.com/watch?v=bctaWQTYHJc&ab_channel=ThePancreasPatient – Video on clinical trials.

https://www.clinicaltrials.gov/ – ClinicalTrials.gov website.

https://www.clinicaltrials.gov/ – Video on rational drug design.



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