African-Americans have a greater risk of developing chronic kidney disease than Americans with European ancestry. Much of this increased risk is explained by two versions of a gene called APOL1 that are common in people with African ancestry. These two versions of the gene, known as G1 and G2, suddenly became much more common in people in sub-Saharan Africa in the last 10,000 years. One theory for their rapid spread is that they might protect against a deadly parasitic disease known as African sleeping sickness. This disease is caused by two related parasites of a species known as Trypanosoma brucei, one of which is found in East Africa, while the other affects West Africa.

Laboratory studies have shown that blood from individuals who carry the G1 and G2 variants is better at killing the East African parasites. However, it is not clear if these gene versions help people living in the rural communities, where African sleeping sickness is common, to fight off the disease.

Now, Cooper, Ilboudo et al. show that G1 and G2 do indeed influence how susceptible individuals in these communities are to African sleeping sickness. Individuals with the G2 version were five-times less likely to get the disease from the East African parasite. Neither version could protect individuals from infection with the West African parasite, but infected individuals with the G1 version had fewer parasites in their blood and were less likely to become severely ill. The ability of the G1 version to control the disease and prolong life could explain why this gene version has become so common amongst people in West Africa.

Unexpectedly, the experiments also revealed that people with the G2 version were more likely to become severely unwell when they were infected by the West African parasite. This indicates that whether this gene variant is helpful or harmful depends on where an individual lives. The next step following on from this work will be to investigate exactly how the G1 version reduces the severity of the West African disease. This may aid the development of new drugs for African sleeping sickness and kidney disease.

Infectious disease is a major driving force of natural selection on human populations. Such evolutionary pressures can select for genetic variants that confer increased resistance to infectious agents, but may also predispose to specific genetic disorders, as exemplified by Plasmodium selection for the sickle-cell trait (Allison, 1954). Like sickle-cell disease, chronic kidney disease also affects millions worldwide (Global Burden of Disease Study 2013 Collaborators, 2015), with a disproportionate risk in populations of recent sub-Saharan African ancestry (National Institutes of Health and National Institute of Diabetes and Digestive and Kidney Diseases, 2010; Norris and Agodoa, 2002; McClellan et al., 1988). In African-Americans a large component of this disparity has been attributed to two common genetic variants of APOL1 (MIM 603743), known as G1 and G2 (Genovese et al., 2010; Tzur et al., 2010). These variants are closely spaced in the C-terminal domain of APOL1 but are located on separate haplotypes (Genovese et al., 2010) (Figure 1). Individuals possessing a high-risk G1/G1, G2/G2 or G1/G2 genotype composed of two risk alleles (approximately 13% of African-Americans [Friedman et al., 2011]), are strongly predisposed to a wide spectrum of chronic kidney disorders that includes focal segmental glomerulosclerosis (Genovese et al., 2010; Kopp et al., 2011), HIV-associated nephropathy (Kopp et al., 2011; Kasembeli et al., 2015) and end-stage renal disease (Genovese et al., 2010; Tzur et al., 2010; Freedman et al., 2014). APOL1 G1 and G2 are prevalent only in populations of recent African heritage (Genovese et al., 2010; Kopp et al., 2011), with evidence for a selective sweep within the last 10,000 years (Genovese et al., 2010), indicative of strong positive selection. Human African trypanosomiasis (HAT), a deadly parasitic disease endemic to sub-Saharan Africa, has been proposed as the source of this positive selective pressure (Genovese et al., 2010). HAT is caused by two tsetse fly-transmitted African trypanosomes, Trypanosoma brucei rhodesiense and T.b. gambiense, which are responsible for the acute East African form and more chronic West Africa form of the disease, respectively (Kennedy, 2013). Both parasites have been responsible for widespread fatal epidemics in sub-Saharan Africa throughout recorded human history (Steverding, 2008) suggesting the potential to exert potent selection pressure on the human genome. A heterozygous advantage model has been proposed for APOL1 G1 and G2 (Genovese et al., 2010) in which recessive susceptibility to chronic kidney disease is balanced by dominant resistance to one or both forms of human African trypanosomiasis.

Figure 1

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Prior to the discovery of its association with kidney disease, APOL1 had already been recognised for encoding the pore-forming serum protein Apolipoprotein L1, which inserts into trypanosome membranes and effectively lyses the Trypanosoma species that cause disease in animals (Vanhamme et al., 2003; Pérez-Morga et al., 2005; Molina-Portela et al., 2005; Thomson and Finkelstein, 2015; Vanwalleghem et al., 2015). However, the two human-infective subspecies have evolved independent mechanisms to resist APOL1-mediated lysis. In T.b. rhodesiense, this is the result of an APOL1-binding protein (Xong et al., 1998; De Greef et al., 1989) whereas for T.b. gambiense the mechanism of APOL1 resistance appears more complex and multifactorial (Capewell et al., 2013; Uzureau et al., 2013; DeJesus et al., 2013; Kieft et al., 2010). It has been hypothesised that APOL1 G1 and G2 variants could overcome one or more of these resistance mechanisms to protect against HAT. Indeed, previous studies have shown that APOL1 G2 (and to a lesser extent G1) plasma is lytic to East African T.b. rhodesiense parasites in vitro (Genovese et al., 2010), but not West African T.b. gambiense (Genovese et al., 2010). Consequently, T.b. rhodesiense is considered the most likely candidate for positive selection of both APOL1 variants in African populations (Genovese et al., 2010). Notably, however, the G1 variant appears significantly less effective at killing T.b. rhodesiense, and is found at very high frequency in West Africa (Genovese et al., 2010; Kopp et al., 2011; Ko et al., 2013; Thomson et al., 2014), where only T.b. gambiense is endemic (Simarro et al., 2010).

Furthermore, a class of asymptomatic individuals has been recently identified in T.b. gambiense disease foci, who exhibit a long-term T.b. gambiense-specific serological response but low or undetectable parasitemia indicative of a latent asymptomatic infection (Koffi et al., 2006; Jamonneau et al., 2012; Bucheton et al., 2011; Ilboudo et al., 2011; Jamonneau et al., 2010; Garcia et al., 2000). Parasites from such individuals appear genetically indistinguishable from those of T.b. gambiense clinical cases (Kaboré et al., 2011), suggesting disease outcome may be mediated by, as yet unidentified, host genetic factors. Field studies are therefore warranted to fully evaluate the contribution of variants of the host protein APOL1 to HAT susceptibility.

Here, we present a retrospective association study to test the relationship between APOL1 G1 and G2 variants and susceptibility to the two different forms of human African trypanosomiasis, T.b. rhodesiense in East Africa and T.b. gambiense in West Africa. In Uganda, an association analysis was performed between T.b. rhodesiense-infected individuals and controls in a major disease focus. In the principal T.b. gambiense focus in Guinea, the presence of both clinical patients and asymptomatic individuals permitted a two-stage analysis. Firstly, the association between APOL1 variants and susceptibility to T.b. gambiense infection (infected versus controls), and secondly the association with disease outcome following infection (clinical cases versus asymptomatic carriage). We report that the association of APOL1 chronic kidney disease variants with HAT susceptibility are markedly different for the two subspecies. As hypothesised, a dominant protective association was detected for the G2 variant against T.b. rhodesiense infection. Conversely, we found that the APOL1 G1 variant was not associated with resistance to T.b. rhodesiense infection, but with protective asymptomatic carriage of T.b. gambiense. We consider the implications of these strikingly different susceptibilities in the context of human co-evolution with African trypanosomes and the distribution, selection and persistence of these kidney disease risk variants in sub-Saharan Africa.

Here, we report the first association study between APOL1 G1 and G2 kidney disease risk variants and T.b. rhodesiense and T.b. gambiense, revealing a more complex relationship with human African trypanosomiasis susceptibility than was originally predicted. The implications of these findings in relation to each of the human-infective parasite subspecies are considered in turn.

The zoonotic T.b. rhodesiense parasite has been responsible for a number of severe HAT outbreaks in recent human history in East Africa that have claimed hundreds of thousands of lives (Hide, 1999; Fèvre et al., 2004). Our data indicate that the APOL1 G2 variant was strongly associated with protection against T.b. rhodesiense infection in a Ugandan disease focus. The observed five-fold reduced susceptibility for individuals possessing a single copy of the APOL1 G2 variant is consistent with laboratory studies reporting in vitro lysis of T.b. rhodesiense for APOL1 G2 plasma and recombinant protein (Genovese et al., 2010), and increased survival of APOL1 G2 transgenic mice in a T.b. rhodesiense infection model (Thomson et al., 2014). T.b. rhodesiense parasites are defined by the potential to express the serum-resistance-associated (SRA) protein (Xong et al., 1998; De Greef and Hamers, 1994) which binds to ancestral APOL1 (G0), inhibiting its formation of lethal pores in trypanosome membranes (Vanhamme et al., 2003; Pérez-Morga et al., 2005; Molina-Portela et al., 2005; Thomson and Finkelstein, 2015; Vanwalleghem et al., 2015). The two-amino acid deletion that characterises the G2 haplotype (rs71785313, [p.N388_Y389del]), is situated within a C-terminal region of APOL1 demonstrated to be essential for SRA binding (Lecordier et al., 2009) (residues 370–392; Figure 1). Studies indicate that G2 shifts the position of a critical lysine residue within the binding region that virtually abolishes the interaction with SRA (Genovese et al., 2010; Thomson et al., 2014). This implicates evasion of the SRA virulence protein as the probable mechanism by which G2 restores APOL1 lytic function and protects the host against T.b. rhodesiense infection. The results of this case-control study add substantial support to the proposed heterozygous advantage model of dominant protection against T.b. rhodesiense infection for this recessive kidney disease risk variant.

For the G1 variant, no protective association against T.b. rhodesiense infection was detected. This finding is somewhat at odds with the reported moderate in vitro T.b. rhodesiense lytic activity for G1 donor plasma and recombinant protein (Genovese et al., 2010), and delayed parasitemia in an APOL1 G1 mouse model (Thomson et al., 2014). Notably however, the trypanolytic effect for G1 in both studies was significantly inferior to the G2 variant by up to several orders of magnitude. The G1 haplotype is composed of two closely positioned missense mutations (rs73885319; [p.S342G] and rs60910145; [p.I384M], Figure 1), of which the latter is also located in the crucial SRA-binding region. However, the rs60910145 point mutation results in an isoleucine to methionine substitution that only slightly weakens SRA-APOL1 interaction (Genovese et al., 2010) and this substitution alone did not extend survival in a mouse model (Thomson et al., 2014). Together these data suggest that the G1 variant is not able to confer substantial protection from T.b. rhodesiense infection. However, our data do not preclude an effect of G1 on the time course or severity of T.b. rhodesiense disease. Additionally, for both the G1 variant and the small number of G2-possessing individuals that were infected with T.b. rhodesiense it is possible that dosage effects or inactivating mutations may be present which have abrogated the trypanolytic ability of these APOL1 variants. No stop codons or mutual non-synonymous variants were observed within the exomes of these individuals during sequence verification of the APOL1 G1 and G2 genotypes (Supplementary file 1), but this possibility cannot be definitively excluded.

In contrast to T.b. rhodesiense, T.b. gambiense primarily infects humans, and is the pathogen responsible for the majority of human disease (Simarro et al., 2010) and significant and widespread epidemics of a slower progressing form of sleeping sickness in Central and West Africa. No lytic ability for either APOL1 variant was reported against T.b. gambiense tested by in vitro assays with donor plasma or recombinant protein (Genovese et al., 2010). Consistent with this observation, in the Guinea focus neither variant demonstrated a resistance association with T.b. gambiense infection. Instead, as summarized in Figure 2A, contrasting associations were observed with infection outcome. APOL1 G1 was associated with a predisposition to latent asymptomatic carriage, while individuals possessing the G2 variant were more likely to progress to clinical disease. The association between APOL1 variants and infection outcome for T.b. gambiense implicates this molecule as a critical modulating factor in disease control. APOL1 is a high-density lipoprotein-associated serum protein, the expression of which is up-regulated by pro-inflammatory stimuli including IFN-γ (Sana et al., 2005) and TNF-α (Monajemi et al., 2002). In accordance with this, APOL1 expression is demonstrably increased during T.b. gambiense infection (Ilboudo et al., 2012). However, no association has been observed between APOL1 expression levels and blood parasite density or clinical outcome of T.b. gambiense infection (Ilboudo et al., 2012). Instead, the results of our study indicate that particular APOL1 variants, rather than modulation of global APOL1 protein level, contribute to differential susceptibility to disease. How these variants influence T.b. gambiense is less perceptible than for T.b. rhodesiense. The mechanism of T.b. gambiense APOL1 resistance does not involve SRA, but three independent contributing components have been implicated: a sub-species-specific protein, TgsGP (Capewell et al., 2013; Uzureau et al., 2013), which alters trypanosome membrane rigidity (Uzureau et al., 2013); reduced uptake of APOL1 (DeJesus et al., 2013 ; Kieft et al., 2010); and proposed faster degradation of APOL1 within the endocytic system of the parasite (Uzureau et al., 2013; Alsford et al., 2014). It is possible that alterations to the APOL1 molecule conferred by G1 and G2 polymorphisms affects one or more of these processes with opposing downstream consequences. Furthermore, the strengthened risk association of G2 with clinical disease when individuals who possess both haplotypes (G1/G2 compound heterozygotes) were excluded indicates a potential dominance for the protective G1 haplotype that might be able to mitigate the disease progressive effects of the G2 variant.

Despite its critical function in human innate resistance to most trypanosomes, the role of APOL1 in T.b. gambiense disease progression appears complex. Contrasting inflammatory cytokine profiles reported between individuals with clinical stage disease and latent carriers (Ilboudo et al., 2014) suggests that an intricate multi-gene interplay between host immune factors, APOL1, and the parasite ultimately determines disease outcome for this subspecies.

For the G1 variant, the relationship with T.b. gambiense appears more akin to the well- established association between Plasmodium and the sickle haemoglobin S (HbS) polymorphism (Allison, 1954). In this classic example of heterozygous advantage, the heterozygous HbS genotype does not protect from Plasmodium infection per se but reduces the risk of severe malaria once infected (Allison, 1954; Taylor et al., 2012). This advantage has selected and maintained prevalence of the HbS polymorphism in malaria-endemic sub-Saharan Africa, despite the high penetrance of life-threatening sickle cell disease in homozygotes (Allison, 1954; Piel et al., 2010). In T.b. gambiense, possession of a G1 allele is associated with the capacity to sustain the asymptomatic latent period of what is normally a fatal disease. This moderation of disease severity could plausibly confer greater survival and reproductive opportunities for individuals possessing the G1 variant than for their G0- or G2-carrying counterparts, who typically progress more rapidly to severe disease (G2 > G0 > G1). Such a selection advantage may explain the high allele frequency of G1 recorded in T.b. gambiense-endemic West Africa (up to 49% (Thomson et al., 2014; Abecasis et al., 2012);Figure 2C), which in some populations exceeds even the maximum global HbS alleles frequencies (Piel et al., 2010). This is consistent with a strong positive selective force on G1 (Genovese et al., 2010), and conceivably, a less powerful opposing deleterious pressure from kidney disease in homozygotes, which is typically of late onset, and incompletely penetrant (Kruzel-Davila et al., 2016).

Population genetics studies of T. brucei indicates that both human-infective sub-species likely arose independently and relatively recently from the animal pathogen T.b. brucei (Tait et al., 1985; Gibson et al., 2002; Balmer et al., 2011; Weir et al., 2016). Molecular clock analysis dates the emergence of T.b. gambiense as a human pathogen in West Africa from a single progenitor approximately 1,000–10,000 years ago (Weir et al., 2016). During this time a pivotal lifestyle transition was occurring with the development of agriculture and larger, more densely populated permanent settlements that provided favorable conditions for the emergence of many animal-derived human pathogens (Harper and Armelagos, 2010; Wolfe et al., 2007). This also coincides with the timeline for a robust selective sweep on G1 detected in the Nigerian Yoruba population (Genovese et al., 2010), at the geographical hotspot for this allele (Figure 2C) in West Africa. A plausible scenario is that within the last 10,000 years an animal-infective T.b. brucei predecessor of T.b. gambiense evolved the essential human serum resistance gene TgsGP (Capewell et al., 2013), facilitating its transmission to humans in the ancestral Bantu population of the Nigeria-Cameroon region. Over time, as T.b. gambiense has undergone progressive adaptation into a predominantly human pathogen (Wolfe et al., 2007), selection for the human APOL1 G1 variant may have occurred in turn, which was able to mitigate the lethal progression of disease and promote long-term asymptomatic carriage. The T.b. gambiense-protective APOL1 G1 haplotype could then have spread with human migration and introgression into other sub-Saharan populations during the Bantu expansions (Tishkoff et al., 2009), or along commercial routes within the last 4000 years, to reach its current distribution across sub-Saharan Africa (Figure 2C).

For APOL1 G2, the increased risk of clinical T.b. gambiense disease contrasts with the strong protective association observed for this variant against T.b. rhodesiense. Puzzlingly, as for G1, some of the highest frequencies of G2 are also found in T.b. gambiense-endemic West Africa (Figure 2D), raising speculation about the evolutionary history of these two variants. Studies of genetic diversity at the APOL1 locus are consistent with a older (2,000–7,000 years), less intensively selected allele (Genovese et al., 2010; Pinto et al., 2016) for G2, and a more recent, rapid sweep for the G1 allele in West Africa (Genovese et al., 2010; Pinto et al., 2016; Limou et al., 2015). One possible interpretation of the available data is that T.b. rhodesiense preceded T.b. gambiense in West Africa and was responsible for driving positive selection of the G2 variant in the Nigeria-Cameroon region. Rising frequencies of this protective variant (or other unrelated epidemiological factors) could have then forced an eastward shift in T.b. rhodesiense endemicity to an approximation of its current distribution in East and Southern Africa. Subsequently, when T.b. gambiense emerged in West Africa, the relative fitness of the APOL1 G2 allele in the exposed population would have been diminished, providing an opportunity for the robust selective sweep of an alternate APOL1 variant, G1, which was able to reduce the disease severity of this new pathogen.

While this is an attractive theory, there is little epidemiological support for a shift in the endemicity of T.b. rhodesiense, which has only been detected in East Africa and has no recorded history in West Africa (Gibson et al., 2002; Radwanska et al., 2002; Balyeidhusa et al., 2012; Picozzi et al., 2005). Moreover, isolates of T.b. rhodesiense from across East Africa show a strong genetic relationship with sympatric T.b. brucei strains, compatible with a predominantly East African origin (Balmer et al., 2011; Godfrey et al., 1990; MacLeod et al., 2001). An alternative model is that selection in favour of the G2 variant may have originated from a different source in West Africa, and it is only more recently, as the G2 variant spread eastwards with the Bantu expansion (Tishkoff et al., 2009), that it has fortuitously proved advantageous against T.b. rhodesiense. Indeed, beyond its proven capacity for trypanolysis, APOL1 was shown to limit Leishmania major infections in mice (Samanovic et al., 2009) and suppress HIV-replication in macrophages (Taylor et al., 2014), hinting at a much broader role for APOL1 in innate immunity to infectious disease.

The association between APOL1 chronic kidney disease risk variants and human African trypanosomiasis reveals a more complex picture of selection and human evolution than was originally hypothesized. Despite their close genetic proximity APOL1 G1 and G2 polymorphisms confer very different, and even opposing, dominant associations with human African trypanosomiasis susceptibility, yet appear convergent in their deleterious recessive contribution to kidney pathology. While the origins of the G2 allele remain speculative, a model of dominant protection against T.b. rhodesiense infection is supported. For G1, the strong West African allele distribution bias and evidence for recent, rapid, positive selection, suggest an alternative evolutionary ancestry for this allele, which we propose involves protection from the lethal consequences of the T.b. gambiense parasite.

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Author details

1. Anneli Cooper

   Wellcome Trust Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

   Contribution

   AC, Formal analysis, Investigation, Methodology, Writing—original draft, Writing—review and editing

   Contributed equally with

   Hamidou Ilboudo, Bruno Bucheton and Annette MacLeod

   Competing interests

   The authors declare that no competing interests exist.

   "This ORCID iD identifies the author of this article:" 0000-0002-1159-142X

2. Hamidou Ilboudo

   1. Centre International de Recherche-Développement sur l'Elevage en zone Subhumide, Bobo-Dioulasso, Burkina Faso
   2. TrypanoGEN, H3Africa Consortium, Makerere University, Kampala, Uganda

   Contribution

   HI, Formal analysis, Investigation, Methodology, Writing—review and editing

   Contributed equally with

   Anneli Cooper, Bruno Bucheton and Annette MacLeod

   Competing interests

   The authors declare that no competing interests exist.

3. V Pius Alibu

   1. TrypanoGEN, H3Africa Consortium, Makerere University, Kampala, Uganda
   2. College of Natural Sciences, Makerere University, Kampala, Uganda

   Contribution

   VPA, Resources, Writing—review and editing

   Competing interests

   The authors declare that no competing interests exist.

4. Sophie Ravel

   Unité Mixte de Recherche IRD-CIRAD 177, Institut de Recherche pour le Développement, Montpellier, France

   Contribution

   SR, Investigation, Writing—review and editing

   Competing interests

   The authors declare that no competing interests exist.

5. John Enyaru

   1. TrypanoGEN, H3Africa Consortium, Makerere University, Kampala, Uganda
   2. College of Natural Sciences, Makerere University, Kampala, Uganda

   Contribution

   JE, Supervision, Writing—review and editing

   Competing interests

   The authors declare that no competing interests exist.

6. William Weir

   Wellcome Trust Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

   Contribution

   WW, Formal analysis, Writing—review and editing

   Competing interests

   The authors declare that no competing interests exist.

7. Harry Noyes

   1. Wellcome Trust Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
   2. TrypanoGEN, H3Africa Consortium, Makerere University, Kampala, Uganda
   3. Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom

   Contribution

   HN, Writing—original draft, Writing—review and editing

   Competing interests

   The authors declare that no competing interests exist.

8. Paul Capewell

   Wellcome Trust Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

   Contribution

   PC, Writing—original draft, Writing—review and editing

   Competing interests

   The authors declare that no competing interests exist.

9. Mamadou Camara

   1. TrypanoGEN, H3Africa Consortium, Makerere University, Kampala, Uganda
   2. Programme National de Lutte contre la Trypanosomiase Humaine Africaine, Conakry, Guinea

   Contribution

   MC, Resources, Writing—review and editing

   Competing interests

   The authors declare that no competing interests exist.

10. Jacqueline Milet

    Unité Mixte de Recherche IRD-CIRAD 177, Institut de Recherche pour le Développement, Montpellier, France

    Contribution

    JM, Investigation, Writing—review and editing

    Competing interests

    The authors declare that no competing interests exist.

11. Vincent Jamonneau

    1. Centre International de Recherche-Développement sur l'Elevage en zone Subhumide, Bobo-Dioulasso, Burkina Faso
    2. TrypanoGEN, H3Africa Consortium, Makerere University, Kampala, Uganda
    3. Unité Mixte de Recherche IRD-CIRAD 177, Institut de Recherche pour le Développement, Montpellier, France

    Contribution

    VJ, Conceptualization, Investigation, Writing—review and editing

    Competing interests

    The authors declare that no competing interests exist.

12. Oumou Camara

    Programme National de Lutte contre la Trypanosomiase Humaine Africaine, Conakry, Guinea

    Contribution

    OC, Project administration, Writing—review and editing

    Competing interests

    The authors declare that no competing interests exist.

13. Enock Matovu

    1. TrypanoGEN, H3Africa Consortium, Makerere University, Kampala, Uganda
    2. College of Veterinary Medicine, Animal Resources and Biosecurity, Makerere University, Kampala, Uganda

    Contribution

    EM, Conceptualization, Resources, Funding acquisition, Writing—review and editing

    Competing interests

    The authors declare that no competing interests exist.

14. Bruno Bucheton

    1. TrypanoGEN, H3Africa Consortium, Makerere University, Kampala, Uganda
    2. Unité Mixte de Recherche IRD-CIRAD 177, Institut de Recherche pour le Développement, Montpellier, France
    3. Programme National de Lutte contre la Trypanosomiase Humaine Africaine, Conakry, Guinea

    Contribution

    BB, Conceptualization, Resources, Funding acquisition, Investigation, Writing—review and editing

    Contributed equally with

    Anneli Cooper, Hamidou Ilboudo and Annette MacLeod

    Competing interests

    The authors declare that no competing interests exist.

15. Annette MacLeod

    1. Wellcome Trust Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
    2. TrypanoGEN, H3Africa Consortium, Makerere University, Kampala, Uganda

    Contribution

    AM, Conceptualization, Funding acquisition, Investigation, Writing—original draft, Writing—review and editing

    Contributed equally with

    Anneli Cooper, Hamidou Ilboudo and Bruno Bucheton

    For correspondence

    annette.macleod@glasgow.ac.uk

    Competing interests

    The authors declare that no competing interests exist.

    "This ORCID iD identifies the author of this article:" 0000-0002-0150-5049

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