Atypical human trypanosomosis: Potentially emerging disease with lack of understanding

Kumar, Rajender; Gupta, S. C.; Bhutia, Wangchuk Dorjee; Vaid, Rajesh Kumar; Kumar, Sanjay

doi:10.1111/zph.12945

Cited by 13 publications

(12 citation statements)

References 80 publications

(178 reference statements)

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“…Trypanosoma evansi (T. evansi), also referred to as Trypanosoma brucei evansi, is a unicellular salivarian protozoan parasite that causes animal trypanosomosis (Surra) and, in rare cases, atypical Human Trypanosomosis (1,2). In livestock as well as murine models, T. evansi infections often trigger a chronic wasting disease hallmarked by anemia, muscle breakdown and weight loss (1,3).…”

Section: Introductionmentioning

confidence: 99%

From helping to regulating – A transcriptomic profile of Ifng+ Il10+ Il21+ Cd4+ Th1 cells indicates their role in regulating inflammation during experimental trypanosomosis

Nguyen

Magez²,

Radwanska³

2023

Front. Trop. Dis

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IntroductionTrypanosoma evansi parasite infections cause a chronic animal wasting disease called Surra, and cases of atypical Human Trypanosomosis (aHT). In experimental models, T. evansi infections are hallmarked by the early onset of excessive inflammation. Therefore, balancing the production of inflammatory cytokines by anti-inflammatory IL-10 is crucial for prolonged survival.MethodsTo improve the understanding of trypanosomosis induced immunopathology, we used scRNA-seq data from an experimental chronic T. evansi infection mouse model, resembling natural infection in terms of disease characteristics. Results and discussionFor the first time, obtained results allowed to assess the transcriptomic profile and heterogeneity of splenic CD4+ T cell subsets, during a trypanosome infection. Here, the predominant subpopulation of T cells was represented by Tbx21(T-bet)+Ccr5+ Id2+ type 1 helper T cells (Th1), followed by Icos+ Cxcr5+Follicular T helper cells (Tfh) and very minor fraction of Il2ra(CD25)+Foxp3+ regulatory T cells (Tregs). Interestingly, the profile of Th1 cells shows that besides Ifng, these cells express high levels of Il10 and Il21, coding for anti-inflammatory and immunoregulatory cytokines. This coincides with the elevated expression of key genes involved in IL-10 and IL-21 secretion pathway such as Stat1 and Stat3, as well as the transcriptional factors Prdm1 (Blimp 1), and Maf (c-Maf). In contrast, there is virtually no IL-10 transcription detected in the Treg population. Finally, differential gene expression and gene ontology analysis of infection-induced Ifng+ Il10+ Il21+ Th1 cells highlights their suppressive function on T cell activation, differentiation and INF-γ production itself. This indicates that during trypanosome infections, the Ifng+ Il10+ Il21+ Th1 cells, rather than Tregs, assume an immune regulatory role that is needed for dampening inflammation.

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Section: Introductionmentioning

confidence: 99%

From helping to regulating – A transcriptomic profile of Ifng+ Il10+ Il21+ Cd4+ Th1 cells indicates their role in regulating inflammation during experimental trypanosomosis

Nguyen

Magez²,

Radwanska³

2023

Front. Trop. Dis

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“…This paper focuses on cases that fit the classical definition of HAT, and it does not include sporadic cases of atypical trypanosomiasis in humans [57,58]. Atypical cases can be due to species of trypanosomes that are different from those usually affecting human beings, the latter being T. b. gambiense and T. b. rhodesiense, as well as T. cruzi as the cause of Chagas disease.…”

Section: Discussionmentioning

confidence: 99%

Human African trypanosomiasis cases diagnosed in non-endemic countries (2011–2020)

et al. 2022

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Background Sleeping sickness, or human African trypanosomiasis (HAT), is transmitted by tsetse flies in endemic foci in sub-Saharan Africa. Because of international travel and population movements, cases are also occasionally diagnosed in non-endemic countries. Methodology/Principal findings Antitrypanosomal medicines to treat the disease are available gratis through the World Health Organization (WHO) thanks to a public-private partnership, and exclusive distribution of the majority of them enables WHO to gather information on all exported cases. Data collected by WHO are complemented by case reports and scientific publications. During 2011–2020, 49 cases of HAT were diagnosed in 16 non-endemic countries across five continents: 35 cases were caused by Trypanosoma brucei rhodesiense, mainly in tourists visiting wildlife areas in eastern and southern Africa, and 14 cases were due to T. b. gambiense, mainly in African migrants originating from or visiting endemic areas in western and central Africa. Conclusions/Significance HAT diagnosis in non-endemic countries is rare and can be challenging, but alertness and surveillance must be maintained to contribute to WHO’s elimination goals. Early detection is particularly important as it considerably improves the prognosis.

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“…Other mechanisms employed by T. b. gambiense Group 1 to escape ApoL1 killing include reduced sensitivity to ApoL1 by cysteine proteases [ 152 ], reduced uptake of ApoL1 due to an L210S substitution in the haptoglobin-hemoglobin receptor, resulting in inactivation [ 151 , 153 ], and increased digestion of ApoL1 [ 142 ]. There have been reports of atypical infections of humans with species of trypanosome not normally infective to humans, including T. lewisi and T. b. evansi , and very rarely T. b. brucei , T. vivax and T. congolense – while sporadic and clearly rare, instances of such infections either are increasing or are being detected more often [ 154 ]. While often the basis for human infectivity in such infections has not been able to be fully investigated, T. b. evansi infections have been identified to occur both in an individual lacking APoL1 due to null mutations [ 155 ], but also recently in a patient with no observable ApoL1 deficiency [ 156 ], suggesting there remain aspects yet to be explained in this intensively studied and important host-parasite interaction.…”

Section: Human Infectivitymentioning

confidence: 99%

Pathogenicity and virulence of African trypanosomes: From laboratory models to clinically relevant hosts

et al. 2023

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African trypanosomes are vector-borne protozoa, which cause significant human and animal disease across sub-Saharan Africa, and animal disease across Asia and South America. In humans, infection is caused by variants of Trypanosoma brucei , and is characterized by varying rate of progression to neurological disease, caused by parasites exiting the vasculature and entering the brain. Animal disease is caused by multiple species of trypanosome, primarily T. congolense , T. vivax, and T. brucei . These trypanosomes also infect multiple species of mammalian host, and this complexity of trypanosome and host diversity is reflected in the spectrum of severity of disease in animal trypanosomiasis, ranging from hyperacute infections associated with mortality to long-term chronic infections, and is also a main reason why designing interventions for animal trypanosomiasis is so challenging. In this review, we will provide an overview of the current understanding of trypanosome determinants of infection progression and severity, covering laboratory models of disease, as well as human and livestock disease. We will also highlight gaps in knowledge and capabilities, which represent opportunities to both further our fundamental understanding of how trypanosomes cause disease, as well as facilitating the development of the novel interventions that are so badly needed to reduce the burden of disease caused by these important pathogens.

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Atypical human trypanosomosis: Potentially emerging disease with lack of understanding

Cited by 13 publications

References 80 publications

From helping to regulating – A transcriptomic profile of Ifng+ Il10+ Il21+ Cd4+ Th1 cells indicates their role in regulating inflammation during experimental trypanosomosis

From helping to regulating – A transcriptomic profile of Ifng+ Il10+ Il21+ Cd4+ Th1 cells indicates their role in regulating inflammation during experimental trypanosomosis

Human African trypanosomiasis cases diagnosed in non-endemic countries (2011–2020)

Pathogenicity and virulence of African trypanosomes: From laboratory models to clinically relevant hosts

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