AMR

introduction
• Trypanosoma is a genus of parasitic protozoa that causes trypanosomiasis, a group of diseases commonly
known as African trypanosomiasis or sleeping sickness in humans and nagana in animals. It is a significant
neglected tropical disease that affects both humans and animals in sub-Saharan Africa, including Ethiopia.

• Up to 70 million cattle in Sub-Saharan Africa are at risk of trypanosomiasis due to drug resistance, resulting in
losses of over $4.5 billion annually to the livestock industry.
• Trypanosomiasis, or African sleeping sickness in humans, is caused by protozoan parasites of the genus
Trypanosoma. It is a serious health and economic issue in Sub-Saharan Africa.

• The disease is transmitted by tsetse flies and can infect both humans and animals like cattle. Trypanosoma
brucei gambiense and T. b. rhodesiense cause sleeping sickness in humans.

• Widespread drug resistance has emerged in the parasite populations over decades of chemotherapy use.
Many first-line drugs are no longer effective in treating trypanosome infections.

• This has had a huge economic impact on the livestock industry, as drug resistance makes it very difficult to
control and treat trypanosomiasis in cattle. Up to 70 million head of cattle are now at risk.

• The annual livestock losses of over $4.5 billion represent a major hindrance to food security and economic
development across Sub-Saharan Africa. Drug resistance has exacerbated what was already a difficult
situation.
 Transmission cycle
• The transmission of Trypanosoma occurs through
the bite of infected tsetse flies (Glossina species),
which are endemic to sub-Saharan Africa. Tsetse
flies serve as both the vector and the host for the
parasite. When an infected tsetse fly bites a
human or animal to feed on blood, it injects the
Trypanosoma parasites into the bloodstream.
The parasites then multiply and spread
throughout the body, causing the disease.
 Species:
• There are two main species of Trypanosoma that primarily affect humans:

• Trypanosoma brucei gambiense: This subspecies causes chronic sleeping sickness in

humans. It is prevalent in West and Central Africa. The disease progresses slowly,
and symptoms may take months or even years to appear.
• Trypanosoma brucei rhodesiense: This subspecies causes acute sleeping sickness in
humans. It is mainly found in East and Southern Africa. The disease progresses
rapidly, and symptoms typically appear within weeks or months.

• In addition to these human-infective subspecies, there are several other

Trypanosoma species that primarily affect animals:

• Trypanosoma congolense: This species causes nagana, a form of trypanosomiasis

that affects livestock, such as cattle, sheep, and goats.
• Trypanosoma vivax: This species also causes nagana in livestock, particularly cattle.
 Regions Most Affected in Sub-Saharan
Africa and Ethiopia:
• Sub-Saharan Africa:
• West and Central Africa: Trypanosoma brucei
gambiense is prevalent in countries such as
Democratic Republic of Congo, Angola, Central
African Republic, and Guinea.
• East and Southern Africa: Trypanosoma brucei
rhodesiense is primarily found in countries
such as Uganda, Tanzania, Malawi, and
Zambia.
 Ethiopia:

• In Ethiopia, trypanosomiasis is predominantly

found in the western and southwestern parts
of the country, where suitable habitats for
tsetse flies exist. Regions such as Gambela,
Benishangul-Gumuz, and Southern Nations,
Nationalities, and Peoples' Region (SNNPR) are
known to have tsetse fly populations and
reported cases of human and animal
trypanosomiasis.
 Trypanosome chemotherapy and
mechanism of action
• Suramin: Suramin is an older drug used to treat the early stage of African trypanosomiasis caused by Trypanosoma brucei
gambiense. Its mechanism of action is not fully understood, but it is thought to inhibit the parasite's energy metabolism
by blocking the enzymes involved in glycolysis, the process by which glucose is metabolized.

• Pentamidine: Pentamidine is used to treat the early stage of African trypanosomiasis caused by Trypanosoma brucei
rhodesiense. It is also used to treat the second stage of the disease caused by both T. brucei gambiense and T. brucei
rhodesiense. Pentamidine enters the parasite and interferes with its DNA and RNA metabolism, ultimately leading to the
parasite's death.

• Melarsoprol: Melarsoprol is an arsenic-containing drug used to treat the late stage of African trypanosomiasis caused by
T. brucei gambiense. It is administered intravenously and crosses the blood-brain barrier to target the parasites in the
central nervous system. Melarsoprol works by inhibiting the parasite's enzymes involved in energy metabolism and
causing oxidative stress, ultimately leading to the parasite's death.

• Eflornithine: Eflornithine is used to treat the late stage of African trypanosomiasis caused by T. brucei gambiense. It acts
by inhibiting the enzyme ornithine decarboxylase, which is involved in the synthesis of polyamines, essential compounds
for the growth and proliferation of the parasite. By blocking this enzyme, eflornithine disrupts the parasite's ability to
replicate and survive.

• Nifurtimox and Benznidazole: Nifurtimox and benznidazole are drugs primarily used to treat Chagas disease, but they
have also shown some effectiveness against Trypanosoma brucei parasites. These drugs are nitroheterocyclic compounds
that undergo metabolic activation within the parasite. The activated forms generate reactive oxygen species that damage
the parasite's DNA and other cellular components, leading to its death.
 Trypanosomes drug resistance
• The development of drug resistance in
Trypanosoma parasites is a complex process
that involves genetic mutations and selection
pressure from the use of anti-trypanosomal
drugs.
Data and Case Studies:
 Sub-Saharan Africa
• According to the World Health Organization (WHO), in 2019, there
were an estimated 977 reported cases of sleeping sickness in Sub-
Saharan Africa, with over 97% of cases occurring in the Democratic
Republic of Congo.
• A study conducted in Uganda revealed that among patients
diagnosed with sleeping sickness, over 20% had a relapse after
treatment due to drug resistance.
• In a case study from the Maasai Mara region in Kenya, animal
trypanosomiasis caused significant livestock losses, with an
estimated 34% of cattle deaths attributed to the disease.
• In Zambia, a study reported that cattle trypanosomiasis led to
annual economic losses of approximately $130 million due to
reduced livestock productivity.
 Ethiopia
• According to the World Health Organization (WHO), Ethiopia
accounted for approximately 2% of reported sleeping sickness
cases in 2019 in Sub-Saharan Africa.
• A study conducted in the Gambella region of Ethiopia identified
drug resistance among Trypanosoma brucei strains, highlighting
the challenge of treatment failure in affected individuals.
• In a case study from the Benishangul-Gumuz region of Ethiopia,
animal trypanosomiasis resulted in significant losses for
livestock farmers, impacting their livelihoods and food security.
• In Ethiopia's Maasai communities, trypanosomiasis has been
identified as a major constraint in cattle production, causing
substantial economic losses.
 Cause of anti-trypanosomal drug resistance
• Genetic Diversity: Trypanosoma parasites have a high level of genetic diversity within their populations. This genetic diversity
is a result of their ability to undergo genetic recombination and mutation. This genetic diversity provides the raw material for
the emergence of drug-resistant strains.

• Selection Pressure: Overuse, misuse, or inadequate treatment practices exert selective pressure on Trypanosoma parasites.
The surviving parasites with inherent or acquired resistance traits have a survival advantage and can proliferate, leading to the
emergence of drug-resistant populations.

• Genetic Mutations: Random genetic mutations can occur naturally in Trypanosoma parasites, including mutations in the genes
that are targeted by anti-trypanosomal drugs. These mutations can alter the structure or function of the drug target,
rendering it less susceptible to the action of the drug.

• Survival and Reproduction: Trypanosomes that possess drug-resistant mutations have a survival advantage when exposed to
the drug. They can continue to multiply and spread within the host, leading to the persistence of the infection and the
potential transmission of drug-resistant strains to other individuals or animals.

• Transmission of Drug Resistance: Drug-resistant Trypanosoma parasites can be transmitted to new hosts, either through the
bite of an infected tsetse fly or through other means of transmission, such as blood transfusion. This transmission allows drug-
resistant strains to spread within the population and potentially replace susceptible strains.

• Treatment Failure: As drug-resistant strains become more prevalent, the effectiveness of anti-trypanosomal drugs diminishes.
The resistant parasites are not eliminated by the drugs, leading to treatment failure and the persistence of the infection.

• Population Dynamics: The movement of animals and humans, including migration and trade, can contribute to the spread of
drug-resistant trypanosomes across regions. Resistant parasites can be introduced into new areas, further amplifying the
resistance problem.
 consequences of Trypanosoma
drug resistance on both Animals
and human health
 Impact on Animal Health
• Livestock Mortality: Trypanosoma parasites cause a disease known as animal
trypanosomiasis or nagana in livestock. Drug resistance can lead to treatment
failure, resulting in increased mortality rates among infected animals. This has
economic implications for farmers and communities that rely on livestock for
income and food security.
• Decreased Productivity: Infected animals may experience reduced productivity,
including weight loss, decreased milk production, and reduced ability to plow or
carry out agricultural activities. This further exacerbates the economic impact
on affected communities.
• Spillover to Wildlife: Trypanosoma parasites can also infect wildlife, contributing
to the transmission cycle. Drug resistance in trypanosomes can affect wildlife
populations, disrupt ecosystems, and impact biodiversity.
• Transmission of Resistant Strains: Drug resistance can also contribute to the
transmission of resistant strains of Trypanosoma, further perpetuating the cycle
of infection and making control efforts more challenging.
 Impact on Human Health
• Increased Morbidity and Mortality: Human African trypanosomiasis, also known
as sleeping sickness, can cause severe neurological symptoms and, if left
untreated, can be fatal. Drug resistance can lead to treatment failure, prolonged
illness, and increased morbidity and mortality rates among affected individuals.
• Transmission of Resistant Strains: Drug resistance can also contribute to the
transmission of resistant strains of Trypanosoma, further perpetuating the cycle
of infection and making control efforts more challenging.
• Impaired Cognitive Function: Trypanosoma infections can cause cognitive
impairments, including difficulties in concentration, memory loss, and behavioral
changes. These cognitive effects can have long-lasting consequences for
individuals and communities, affecting productivity and quality of life.
• Economic Burden: The disease's impact on individuals' health and productivity,
combined with the costs of diagnosis and treatment, imposes a significant
economic burden on affected communities and healthcare systems.
 Challenges in Diagnosis, Treatment, and
Management:
• Limited Diagnostic Tools: Diagnosis of trypanosomiasis relies on specialized
laboratory techniques, which may not be readily available in resource-limited
settings. This leads to delays in diagnosis and treatment initiation.
• Access to Treatment: Limited access to effective trypanosomiasis treatment is a
major challenge. Inadequate healthcare infrastructure, limited availability of
medications, and financial constraints hinder access to treatment for affected
individuals and communities.
• Drug Toxicity and Side Effects: Some trypanosomiasis medications, such as
melarsoprol and eflornithine, can have severe side effects and toxicity. This
poses challenges in managing the disease, as the risks and benefits of treatment
must be carefully considered.
• Drug Resistance Surveillance: Monitoring and surveillance of drug resistance in
Trypanosoma parasites are crucial but can be limited in resource-limited
settings. This hampers the ability to detect and respond to emerging drug
resistance.
 Zoonotic Transmission
• Trypanosoma parasites, the causative agents
of trypanosomiasis, have a zoonotic nature,
which means they can be transmitted
between humans and animals. This interplay
between human and animal health is
significant in understanding and addressing
the disease
 Animal-to-Human Transmission:
• Trypanosoma parasites, such as Trypanosoma
brucei gambiense and Trypanosoma brucei
rhodesiense, can be transmitted to humans
through the bite of infected tsetse flies. When
these flies feed on infected animals, they
acquire the parasites, and subsequent bites on
humans can lead to human infection.
 Human-to-Animal Transmission:
• Humans infected with Trypanosoma brucei
can transmit the parasite to animals,
particularly through blood-to-blood contact.
This can occur, for example, through the use
of contaminated needles or instruments
during veterinary procedures, blood
transfusions, or traditional practices involving
animal handling.
 One Health Approach:
• The One Health approach recognizes the
interconnectedness of human, animal, and
environmental health. Implementing integrated
surveillance and control strategies that consider
both human and animal populations is essential
to effectively manage trypanosomiasis.
Collaboration between human health, veterinary,
and environmental sectors is needed to address
the disease comprehensively.
 Benefits of a One Health Approach
• Early Detection and Prompt Treatment: Integrated surveillance allows for early detection of
trypanosomiasis cases in both humans and animals. Early diagnosis enables timely treatment, reducing
the risk of severe disease outcomes, and preventing further transmission.

• Vector Control: Tsetse fly control is a critical component of integrated strategies. Targeting tsetse fly
populations through vector control measures, such as insecticide-treated traps, insecticide-treated
livestock, and habitat management, helps reduce the risk of transmission to both humans and animals.
• Enhanced Surveillance: Integrated surveillance systems that monitor both human and animal
populations allow for early detection of drug-resistant Trypanosoma strains. This enables timely
intervention and prevents the spread of resistance.

• Research Collaboration: Joint research efforts between human health and veterinary sectors facilitate a
better understanding of Trypanosoma drug resistance mechanisms and the development of innovative
treatment strategies. Collaborative research also helps identify emerging resistance patterns and guides
policy decisions.

• Coordinated Treatment Strategies: A One Health approach ensures that treatment strategies are aligned
between human and animal health sectors. Coordinated efforts prevent the spread of drug-resistant
parasites between humans and animals and optimize the use of available treatment options.
 Examples of Successful One Health
Initiatives:
• Southern and Eastern Africa Network for Trypanosomiasis (SEANET): SEANET is a regional network that
promotes collaboration among human and animal health professionals, researchers, and policymakers.
It focuses on sharing information, coordinating surveillance, and implementing joint control strategies
for trypanosomiasis.

• HAT Platform: The Human African Trypanosomiasis (HAT) Platform is a partnership between the World
Health Organization (WHO) and the Drugs for Neglected Diseases initiative (DNDi). It aims to improve
the management of sleeping sickness by integrating human and animal health services, strengthening
surveillance, and supporting research and development of new drugs.

• REVAMP Project: The Research and Evidence for Veterinary Advancements in the Mekong Region
(REVAMP) project in Southeast Asia is an example of a One Health initiative addressing trypanosomiasis.
It focuses on enhancing the surveillance of trypanosomiasis in both humans and animals, improving
diagnostic capacity, and promoting collaboration between human and animal health sectors.

• Uganda Trypanosomiasis Control Council (UTCC): UTCC is a national initiative in Uganda that brings
together stakeholders from human health, veterinary, and research sectors to coordinate efforts in
trypanosomiasis control. It integrates surveillance, treatment, and vector control strategies to combat
the disease.
 In Ethiopia
• One Health Central and Eastern Africa (OHCEA): OHCEA is a regional initiative that promotes collaboration and capacity building in
One Health approaches. In Ethiopia, OHCEA has facilitated partnerships between universities, research institutions, and government
agencies to address zoonotic diseases, including Trypanosomiasis. It has supported joint surveillance, research, and training
programs, strengthening the country's ability to respond to public health threats.

• Ethiopian Sheep and Goat Productivity Improvement Program (ESGPIP): ESGPIP is a national initiative aimed at improving the
productivity and health of small ruminants. The program recognizes the interdependence of human and animal health and
incorporates One Health principles into its activities. By providing veterinary services, promoting animal disease control, and
enhancing livestock productivity, ESGPIP contributes to improving livelihoods and reducing the burden of zoonotic diseases.

• Enhancing Dairy Value Chain Project (EDVCP): EDVCP is a collaborative effort between the government of Ethiopia, the International
Livestock Research Institute (ILRI), and other partners. The project focuses on enhancing the dairy value chain, including milk
production, processing, and marketing. By integrating animal health services, such as vaccination and disease control, with
interventions to improve milk quality and hygiene, EDVCP enhances both human and animal health outcomes.

• Ethiopian Public Health Institute (EPHI): EPHI is a national research institution that plays a crucial role in One Health initiatives. It
conducts research on zoonotic diseases, including Trypanosomiasis, and provides technical support to the government in developing
policies and strategies. EPHI collaborates with various stakeholders, including the Ministry of Health and the Ministry of Agriculture,
to strengthen surveillance, diagnostics, and control measures for zoonotic diseases.

• Sustainable Control of Taenia solium (Cysticercosis and Neurocysticercosis) in Ethiopia (Scolex): Scolex is a research project
implemented by the University of Bergen, Norway, in collaboration with Ethiopian partners. The project focuses on addressing the
public health and socioeconomic impacts of Taenia solium, a zoonotic parasite causing cysticercosis and neurocysticercosis. Scolex
employs a One Health approach by integrating human health, veterinary, and environmental interventions to control the disease
and raise awareness among communities.
 Recommendation
• Addressing Evolving Drug Resistance: Trypanosoma parasites have shown the ability to develop resistance to existing drugs. Continued research
helps identify emerging resistance patterns and understand the underlying mechanisms. This knowledge is vital for designing targeted
interventions that can overcome or prevent resistance.

• Developing New Drugs: Research efforts aim to discover and develop novel drugs with different mechanisms of action. These drugs can be
effective against drug-resistant strains and offer alternative treatment options. By exploring new compounds and drug combinations, researchers
can enhance treatment efficacy and reduce the risk of resistance development.

• Optimizing Drug Combinations: Combination therapies, which involve the simultaneous use of multiple drugs, have shown promise in combating
drug resistance. Research helps identify synergistic drug combinations that can enhance treatment outcomes by targeting different stages of the
Trypanosoma life cycle or employing drugs with distinct mechanisms of action.

• Improving Diagnostics: Research focuses on developing more accurate, affordable, and accessible diagnostic tools for Trypanosoma infections.
Rapid diagnostic tests, advanced molecular techniques, and point-of-care devices can enable early detection of infections and drug resistance.
Timely diagnosis allows for prompt treatment, reducing the risk of severe disease outcomes and limiting the spread of resistance.

• Targeting Specific Molecular Pathways: Understanding the molecular pathways involved in Trypanosoma drug resistance allows researchers to
identify potential targets for intervention. By developing drugs that specifically target these pathways, researchers can inhibit the mechanisms
underlying resistance and improve treatment outcomes.

• Integrated Approaches: Research promotes the development of integrated strategies that consider multiple aspects of disease control. This
includes combining vector control measures, such as insecticide-treated traps or livestock, with drug treatment strategies. Integrated approaches
can effectively break the transmission cycle and reduce the risk of drug resistance emergence.

• Capacity Building: Research and innovation activities contribute to capacity building in affected regions. They foster collaborations between local
researchers, international organizations, and policymakers, enhancing knowledge exchange, skill development, and the implementation of
effective control programs.
 Conclusion
• addressing Trypanosoma drug resistance in Sub-Saharan Africa requires a comprehensive and urgent
response through a One Health approach. The integration of human and veterinary healthcare efforts,
joint surveillance, research collaboration, and coordinated treatment strategies are paramount in
effectively combating this challenge.

• By highlighting the benefits of interdisciplinary collaboration and the successful One Health initiatives in
the region, we recognize the importance of working together to achieve better outcomes. Ongoing
research and innovation play a critical role in developing new drugs, diagnostics, and treatment
strategies, including novel approaches such as combination therapies and targeted interventions.

• However, the need for action extends beyond research. We must advocate for funding and policy
changes that prioritize One Health approaches, support capacity building, and strengthen surveillance
and diagnostic capabilities. Active participation in awareness campaigns will help educate communities
and bridge the gap between human and animal health sectors.

• The urgency of addressing Trypanosoma drug resistance cannot be overstated. By supporting

interdisciplinary collaboration, advocating for funding and policy changes, and participating in
awareness campaigns, we can make a tangible difference. Let us unite in our commitment to a
comprehensive and One Health approach, and together, we can overcome Trypanosoma drug
resistance, safeguarding the health and well-being of communities in Sub-Saharan Africa.
•Thank you