Challenges for the Implementation
of Fexinidazole to Beat Sleeping
Sickness in Uganda
A research about the oral treatment with Fexinidazole as a solution to
Human African Trypanosomiasis (HAT) in Uganda, as compared to DRC
Names Lieve Mijnster (6944302)
Robert-Jan Duit (6522092)
Yara Langeveld (6733506)
Course Sustainability, Health and Innovation (GEO3-2266)
Faculty Geosciences - Utrecht University
Date November 5 2021
Word count 5492
,Table of contents
Table of contents 2
Abstract 3
Abbreviations 3
Introduction 4
Theory 6
TIS-analysis 6
GIS-analysis 7
Method 8
Research design 9
Operationalisation 9
Data collection 11
Data analysis 12
Validity and reliability 12
Results 14
Structural analysis 14
Phase of development 17
Functional analysis 17
Systemic failures 20
Policy instruments 22
Conclusion 23
Discussion 24
References 25
Appendix A: Interview guide 29
Appendix B: Interview summary and transcript 31
B1: Summary 31
B2: Transcript 31
B3: Data structure 38
,Abstract
To treat patients suffering from the life-threatening, neglected, tropical disease Human African
Trypanosomiasis (HAT) in Uganda, also known as sleeping sickness, the innovative treatment
Fexinidazole can be used. This oral treatment has several advantages over competitive treatments
and has already been successfully implemented in DRC. However, a nationwide distribution has not
yet been achieved in Uganda. This research aims to discover what the main barriers are to the
implementation of this treatment in Uganda. To accomplish this, both the technological aspects of
Fexinidazole and the connection to the global system surrounding it are analysed. Information is
gathered qualitatively through an extensive interview and literature search. After a structural analysis
of the involved actors, institutions, networks and technological factors, four system functions are
analysed; entrepreneurial activity, knowledge exchange, guidance of the search and counteracting
resistance to change. The results indicate three of these form a medium of high barrier to the
implementation of Fexinidazole, whereby only knowledge exchange is excluded. Based on these
system barriers, it can be recommended to the Ugandan government to include Fexinidazole in their
national treatment guidelines and to participate in the training programmes of WHO and DNDi. This
way, proper diagnosis and treatment and raising awareness among the population can be stimulated
and Uganda can successfully beat HAT by using Fexinidazole.
Abbreviations
Table 1. Commonly used abbreviations§
, Introduction
Human African Trypanosomiasis (HAT), commonly referred to as sleeping sickness, is a
life-threatening, neglected, tropical disease caused by two parasite strains; Trypanosoma brucei
gambiense and Trypanosoma brucei rhodesiense (DNDi, 2020a; Smith et al., 1998). T.b. gambiense
accounts for 95% of the reported cases and induces a chronic infection, while T.b. rhodesiense
accounts for the remaining 5% and leads to an acute infection (WHO, 2021). HAT is transmitted by
the tsetse fly and causes severe headaches, insomnia, muscle and joint pain, enlarged lymph nodes
and skin rash (IAMAT, 2020). This research will focus on T.b. gambiense. In the first stage, the parasite
multiplies in blood, tissue and lymph, whereafter it crosses the blood-brain barrier and infects the
central nervous system (WHO, 2021). Without proper treatment, HAT is fatal (DNDi, 2020a).
An important current treatment for HAT is the oral medicine Fexinidazole, which was included in the
World Health Organization (WHO) Essential Medicines List (EML) and WHO HAT treatment guidelines
in 2019 (WHO, 2021). It is the first treatment applicable to both stages of T.b. gambiense and
involves a ten-day once-a-day treatment (DNDi, 2021a). The drug development and diffusion of
Fexinidazole started in 2005 and ended in 2018 after approval from the European Medicine Agency
(EMA) (EMA, 2021; DNDi, 2021b). It is a DNA synthesis inhibitor developed by international
pharmaceutical group Sanofi and the non-profit organisation Drugs for Neglected Diseases initiative
(DNDi) costing 55 million euros (Deeks, 2019; DNDi, 2021b).
Fexinidazole is donated by Sanofi to the WHO for national HAT control programs in endemic
countries and a submission is planned for Uganda to exterminate HAT (TDR, n.d.; DNDi, 2021a).
Firstly, a Technological Innovation System (TIS) analysis is used to analyse the health system in
Uganda and the bottlenecks to the adoption of Fexinidazole (Hekkert et al., 2011). In addition, a
coupling with a Global Innovation System (GIS) analysis provides insight into a more global
perspective of using Fexinidazole in different countries (Binz & Truffer, 2017).
In the Democratic Republic of Congo (DRC) the distribution of Fexinidazole started in December 2018
(DNDi, 2021b). It has changed the life of HAT-patients as it is available for use outside hospitals and
the WHO launched visibility campaigns, which increases access (TDR, n.d.). Through this, inhabitants
and authorities fear the disease less, enabling a smooth implementation of Fexinidazole in DRC.
This research aims to clarify the bottlenecks in the adoption of Fexinidazole in Uganda to increase
access to this medicine. The following research question will be answered: “What are the challenges
in the Fexinidazole innovation system as a treatment for HAT in Uganda, as compared to DRC?” The
situation is analysed over a period of sixteen years (2005-2021), because this involves the discovery
and development of Fexinidazole. By using both a TIS and GIS, guidelines are provided for global and
local health organisations. This will provide a unique, theoretical contribution, as a TIS and GIS are
applied to a medical innovation. On a societal level, this research will provide a practical contribution,
as the insights into the barriers of the Fexinidazole implementation in Uganda can be used to
improve access to effective medicines in other endemic countries.
of Fexinidazole to Beat Sleeping
Sickness in Uganda
A research about the oral treatment with Fexinidazole as a solution to
Human African Trypanosomiasis (HAT) in Uganda, as compared to DRC
Names Lieve Mijnster (6944302)
Robert-Jan Duit (6522092)
Yara Langeveld (6733506)
Course Sustainability, Health and Innovation (GEO3-2266)
Faculty Geosciences - Utrecht University
Date November 5 2021
Word count 5492
,Table of contents
Table of contents 2
Abstract 3
Abbreviations 3
Introduction 4
Theory 6
TIS-analysis 6
GIS-analysis 7
Method 8
Research design 9
Operationalisation 9
Data collection 11
Data analysis 12
Validity and reliability 12
Results 14
Structural analysis 14
Phase of development 17
Functional analysis 17
Systemic failures 20
Policy instruments 22
Conclusion 23
Discussion 24
References 25
Appendix A: Interview guide 29
Appendix B: Interview summary and transcript 31
B1: Summary 31
B2: Transcript 31
B3: Data structure 38
,Abstract
To treat patients suffering from the life-threatening, neglected, tropical disease Human African
Trypanosomiasis (HAT) in Uganda, also known as sleeping sickness, the innovative treatment
Fexinidazole can be used. This oral treatment has several advantages over competitive treatments
and has already been successfully implemented in DRC. However, a nationwide distribution has not
yet been achieved in Uganda. This research aims to discover what the main barriers are to the
implementation of this treatment in Uganda. To accomplish this, both the technological aspects of
Fexinidazole and the connection to the global system surrounding it are analysed. Information is
gathered qualitatively through an extensive interview and literature search. After a structural analysis
of the involved actors, institutions, networks and technological factors, four system functions are
analysed; entrepreneurial activity, knowledge exchange, guidance of the search and counteracting
resistance to change. The results indicate three of these form a medium of high barrier to the
implementation of Fexinidazole, whereby only knowledge exchange is excluded. Based on these
system barriers, it can be recommended to the Ugandan government to include Fexinidazole in their
national treatment guidelines and to participate in the training programmes of WHO and DNDi. This
way, proper diagnosis and treatment and raising awareness among the population can be stimulated
and Uganda can successfully beat HAT by using Fexinidazole.
Abbreviations
Table 1. Commonly used abbreviations§
, Introduction
Human African Trypanosomiasis (HAT), commonly referred to as sleeping sickness, is a
life-threatening, neglected, tropical disease caused by two parasite strains; Trypanosoma brucei
gambiense and Trypanosoma brucei rhodesiense (DNDi, 2020a; Smith et al., 1998). T.b. gambiense
accounts for 95% of the reported cases and induces a chronic infection, while T.b. rhodesiense
accounts for the remaining 5% and leads to an acute infection (WHO, 2021). HAT is transmitted by
the tsetse fly and causes severe headaches, insomnia, muscle and joint pain, enlarged lymph nodes
and skin rash (IAMAT, 2020). This research will focus on T.b. gambiense. In the first stage, the parasite
multiplies in blood, tissue and lymph, whereafter it crosses the blood-brain barrier and infects the
central nervous system (WHO, 2021). Without proper treatment, HAT is fatal (DNDi, 2020a).
An important current treatment for HAT is the oral medicine Fexinidazole, which was included in the
World Health Organization (WHO) Essential Medicines List (EML) and WHO HAT treatment guidelines
in 2019 (WHO, 2021). It is the first treatment applicable to both stages of T.b. gambiense and
involves a ten-day once-a-day treatment (DNDi, 2021a). The drug development and diffusion of
Fexinidazole started in 2005 and ended in 2018 after approval from the European Medicine Agency
(EMA) (EMA, 2021; DNDi, 2021b). It is a DNA synthesis inhibitor developed by international
pharmaceutical group Sanofi and the non-profit organisation Drugs for Neglected Diseases initiative
(DNDi) costing 55 million euros (Deeks, 2019; DNDi, 2021b).
Fexinidazole is donated by Sanofi to the WHO for national HAT control programs in endemic
countries and a submission is planned for Uganda to exterminate HAT (TDR, n.d.; DNDi, 2021a).
Firstly, a Technological Innovation System (TIS) analysis is used to analyse the health system in
Uganda and the bottlenecks to the adoption of Fexinidazole (Hekkert et al., 2011). In addition, a
coupling with a Global Innovation System (GIS) analysis provides insight into a more global
perspective of using Fexinidazole in different countries (Binz & Truffer, 2017).
In the Democratic Republic of Congo (DRC) the distribution of Fexinidazole started in December 2018
(DNDi, 2021b). It has changed the life of HAT-patients as it is available for use outside hospitals and
the WHO launched visibility campaigns, which increases access (TDR, n.d.). Through this, inhabitants
and authorities fear the disease less, enabling a smooth implementation of Fexinidazole in DRC.
This research aims to clarify the bottlenecks in the adoption of Fexinidazole in Uganda to increase
access to this medicine. The following research question will be answered: “What are the challenges
in the Fexinidazole innovation system as a treatment for HAT in Uganda, as compared to DRC?” The
situation is analysed over a period of sixteen years (2005-2021), because this involves the discovery
and development of Fexinidazole. By using both a TIS and GIS, guidelines are provided for global and
local health organisations. This will provide a unique, theoretical contribution, as a TIS and GIS are
applied to a medical innovation. On a societal level, this research will provide a practical contribution,
as the insights into the barriers of the Fexinidazole implementation in Uganda can be used to
improve access to effective medicines in other endemic countries.
