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Frontiers in Immunology 2019Trypanosomiasis has been recognized as a scourge in sub-Saharan Africa for centuries. The disease, caused by protozoan parasites of the genus, is a major cause of... (Review)
Review
Trypanosomiasis has been recognized as a scourge in sub-Saharan Africa for centuries. The disease, caused by protozoan parasites of the genus, is a major cause of mortality and morbidity in animals and man. Human African trypanosomiasis (HAT), or sleeping sickness, results from infections with or with accounting for over 95% of infections. Historically there have been major epidemics of the infection, followed by periods of relative disease control. As a result of concerted disease surveillance and treatment programmes, implemented over the last two decades, there has been a significant reduction in the number of cases of human disease reported. However, the recent identification of asymptomatic disease carriers gives cause for some concern. The parasites evade the host immune system by switching their surface coat, comprised of variable surface glycoprotein (VSG). In addition, they have evolved a variety of strategies, including the production of serum resistance associated protein (SRA) and -specific glycoprotein (TgsGP) to counter host defense molecules. Infection with either disease variant results in an early haemolymphatic-stage followed by a late encephalitic-stage when the parasites migrate into the CNS. The clinical features of HAT are diverse and non-specific with early-stage symptoms common to several infections endemic within sub-Saharan Africa which may result in a delayed or mistaken diagnosis. Migration of the parasites into the CNS marks the onset of late-stage disease. Diverse neurological manifestations can develop accompanied by a neuroinflammatory response, comprised of astrocyte activation, and inflammatory cell infiltration. However, the transition between the early and late-stage is insidious and accurate disease staging, although crucial to optimize chemotherapy, remains problematic with neurological symptoms and neuroinflammatory changes recorded in early-stage infections. Further research is required to develop better diagnostic and staging techniques as well as safer more efficacious drug regimens. Clearer information is also required concerning disease pathogenesis, specifically regarding asymptomatic carriers and the mechanisms employed by the trypanosomes to facilitate progression to the CNS and precipitate late-stage disease. Without progress in these areas it may prove difficult to maintain current control over this historically episodic disease.
Topics: Animals; Antiprotozoal Agents; Blood-Brain Barrier; Brain; Delayed Diagnosis; Humans; Incidence; Neglected Diseases; Pentamidine; Severity of Illness Index; Suramin; Treatment Outcome; Trypanosoma brucei gambiense; Trypanosoma brucei rhodesiense; Trypanosomiasis, African
PubMed: 30740102
DOI: 10.3389/fimmu.2019.00039 -
Trends in Parasitology Mar 2018Trypanosoma brucei gambiense causes human African trypanosomiasis (HAT). Between 1990 and 2015, almost 440000 cases were reported. Large-scale screening of populations... (Review)
Review
Trypanosoma brucei gambiense causes human African trypanosomiasis (HAT). Between 1990 and 2015, almost 440000 cases were reported. Large-scale screening of populations at risk, drug donations, and efforts by national and international stakeholders have brought the epidemic under control with <2200 cases in 2016. The World Health Organization (WHO) has set the goals of gambiense-HAT elimination as a public health problem for 2020, and of interruption of transmission to humans for 2030. Latent human infections and possible animal reservoirs may challenge these goals. It remains largely unknown whether, and to what extend, they have an impact on gambiense-HAT transmission. We argue that a better understanding of the contribution of human and putative animal reservoirs to gambiense-HAT epidemiology is mandatory to inform elimination strategies.
Topics: Animals; Disease Eradication; Disease Reservoirs; Humans; Risk Factors; Trypanosoma brucei gambiense; Trypanosomiasis, African
PubMed: 29396200
DOI: 10.1016/j.pt.2017.11.008 -
Journal of Neurology Sep 2019Human African trypanosomiasis (HAT), also known as sleeping sickness, is one of the Africa's 'neglected diseases' and is caused by infection with protozoan parasites of... (Review)
Review
Human African trypanosomiasis (HAT), also known as sleeping sickness, is one of the Africa's 'neglected diseases' and is caused by infection with protozoan parasites of the Trypanosoma genus. Transmitted by the bite of the tsetse fly, it puts 70 million people at risk throughout sub-Saharan Africa and is usually fatal if untreated or inadequately treated. In this brief overview, some important recent developments in this disease are outlined. These cover various aspects including a reduction in disease incidence, newly recognised parasite reservoir sites in humans, disease outcome, novel diagnostic methods, new and improved treatment, and disease neuropathogenesis.
Topics: Animals; Benzamides; Boron Compounds; Humans; Neglected Diseases; Trypanosoma brucei gambiense; Trypanosoma brucei rhodesiense; Trypanosomiasis, African
PubMed: 31209574
DOI: 10.1007/s00415-019-09425-7 -
Frontiers in Immunology 2019Parasites, including African trypanosomes, utilize several immune evasion strategies to ensure their survival and completion of their life cycles within their hosts. The... (Review)
Review
Parasites, including African trypanosomes, utilize several immune evasion strategies to ensure their survival and completion of their life cycles within their hosts. The defense factors activated by the host to resolve inflammation and restore homeostasis during active infection could be exploited and/or manipulated by the parasites in an attempt to ensure their survival and propagation. This often results in the parasites evading the host immune responses as well as the host sustaining some self-inflicted collateral tissue damage. During infection with African trypanosomes, both effector and suppressor cells are activated and the balance between these opposing arms of immunity determines susceptibility or resistance of infected host to the parasites. Immune evasion by the parasites could be directly related to parasite factors, (e.g., antigenic variation), or indirectly through the induction of suppressor cells following infection. Several cell types, including suppressive macrophages, myeloid-derived suppressor cells (MDSCs), and regulatory T cells have been shown to contribute to immunosuppression in African trypanosomiasis. In this review, we discuss the key factors that contribute to immunity and immunosuppression during infection, and how these factors could aid immune evasion by African trypanosomes. Understanding the regulatory mechanisms that influence resistance and/or susceptibility during African trypanosomiasis could be beneficial in designing effective vaccination and therapeutic strategies against the disease.
Topics: Animals; Humans; Immune Evasion; Macrophages; Myeloid-Derived Suppressor Cells; Protozoan Vaccines; T-Lymphocytes, Regulatory; Trypanosoma congolense; Trypanosomiasis, African
PubMed: 31824512
DOI: 10.3389/fimmu.2019.02738 -
Current Opinion in Microbiology Dec 2019Many microbial eukaryotes exhibit cell-cell communication to co-ordinate group behaviours as a strategy to exploit a changed environment, adapt to adverse conditions or... (Review)
Review
Many microbial eukaryotes exhibit cell-cell communication to co-ordinate group behaviours as a strategy to exploit a changed environment, adapt to adverse conditions or regulate developmental responses. Although best characterised in bacteria, eukaryotic microbes have also been revealed to cooperate to optimise their survival or dissemination. An excellent model for these processes are African trypanosomes, protozoa responsible for important human and animal disease in sub Saharan Africa. These unicellular parasites use density sensing in their mammalian host to prepare for transmission. Recently, the signal and signal transduction pathway underlying this activity have been elucidated, revealing that the parasite exploits oligopeptide signals generated by released peptidases to monitor cell density and so generate transmission stages. Here we review the evidence for this elegant quorum sensing mechanism and its parallels with similar mechanisms in other microbial systems. We also discuss its implications for disease spread in the context of coinfections involving different trypanosome species.
Topics: Africa South of the Sahara; Animals; Coinfection; Humans; Quorum Sensing; Signal Transduction; Trypanosoma brucei brucei; Trypanosomiasis, African
PubMed: 31442903
DOI: 10.1016/j.mib.2019.07.001 -
Journal of Cellular Physiology Jun 2022African trypanosomes are early branching protists that cause human and animal diseases, termed trypanosomiases. They have been under intensive study for more than 100... (Review)
Review
African trypanosomes are early branching protists that cause human and animal diseases, termed trypanosomiases. They have been under intensive study for more than 100 years and have contributed significantly to our understanding of eukaryotic biology. The combination of conserved and parasite-specific features mean that their flagellum has gained particular attention. Here, we discuss the different structural features of the flagellum and their role in transmission and virulence. We highlight the possibilities of targeting flagellar function to cure trypanosome infections and help in the fight to eliminate trypanosomiases.
Topics: Animals; Flagella; Trypanosoma; Trypanosomiasis; Trypanosomiasis, African; Virulence
PubMed: 35616248
DOI: 10.1002/jcp.30778 -
Parasites & Vectors Jan 2021In the 1980s and 1990s, great strides were taken towards the elimination of tsetse and animal African trypanosomiasis (AAT) in Zimbabwe. However, advances in recent...
BACKGROUND
In the 1980s and 1990s, great strides were taken towards the elimination of tsetse and animal African trypanosomiasis (AAT) in Zimbabwe. However, advances in recent years have been limited. Previously freed areas have been at risk of reinvasion, and the disease in tsetse-infested areas remains a constraint to food security. As part of ongoing control activities, monitoring of tsetse and AAT is performed regularly in the main areas at risk. However, a centralized digital archive is missing. To fill this gap, a spatially explicit, national-level database of tsetse and AAT (i.e. atlas) was established through systematic data collation, harmonization and geo-referencing for the period 2000-2019.
METHODS
The atlas covers an area of approximately 70,000 km, located mostly in the at-risk areas in the north of the country. In the tsetse component, a total of 33,872 entomological records were assembled for 4894 distinct trap locations. For the AAT component, 82,051 samples (mainly dry blood smears from clinically suspicious animals) were collected at 280 diptanks and examined for trypanosomal infection by microscopy.
RESULTS
Glossina pallidipes (82.7% of the total catches) and Glossina morsitans morsitans (17.3%) were the two tsetse species recorded in the north and northwest parts of the country. No fly was captured in the northeast. The distribution of AAT follows broadly that of tsetse, although sporadic AAT cases were also reported from the northeast, apparently because of transboundary animal movement. Three trypanosome species were reported, namely Trypanosoma brucei (61.7% of recorded infections), Trypanosoma congolense (28.1%) and Trypanosoma vivax (10.2%). The respective prevalences, as estimated in sentinel herds by random sampling, were 2.22, 0.43 and 0.30%, respectively.
DISCUSSION
The patterns of tsetse and AAT distributions in Zimbabwe are shaped by a combination of bioclimatic factors, historical events such as the rinderpest epizootic at the turn of the twentieth century and extensive and sustained tsetse control that is aimed at progressively eliminating tsetse and trypanosomiasis from the entire country. The comprehensive dataset assembled in the atlas will improve the spatial targeting of surveillance and control activities. It will also represent a valuable tool for research, by enabling large-scale geo-spatial analyses.
Topics: Animal Distribution; Animals; Atlases as Topic; Databases, Factual; Insect Vectors; Livestock; Trypanosoma; Trypanosomiasis, African; Tsetse Flies; Zimbabwe
PubMed: 33446276
DOI: 10.1186/s13071-020-04555-8 -
Current Opinion in Infectious Diseases Oct 2022Gambiense human African trypanosomiasis (gHAT), a disease that has killed hundreds of thousands as recently as the 1990s, could be on the verge of elimination or even... (Review)
Review
PURPOSE OF REVIEW
Gambiense human African trypanosomiasis (gHAT), a disease that has killed hundreds of thousands as recently as the 1990s, could be on the verge of elimination or even eradication. This review describes recent developments that give us reasons for optimism as well as some caveats.
RECENT FINDINGS
New developments in diagnostic and vector control tools, and especially in treatment, make it possible to strive for elimination of transmission of gHAT by 2030, perhaps even eradication.
SUMMARY
Gambiense human African trypanosomiasis is a deadly infectious disease affecting West and Central Africa, South Sudan and Uganda, and transmitted between humans by tsetse flies. The disease has caused several major epidemics, the latest one in the 1990s. Thanks to recent innovations such as rapid diagnostic tests for population screening, a single-dose oral treatment and a highly efficient vector control strategy, interruption of transmission of the causative parasite is now within reach. If indeed gHAT has an exclusively human reservoir, this could even result in eradication of the disease. Even if there were an animal reservoir, on the basis of epidemiological data, it plays a limited role. Maintaining adequate postelimination surveillance in known historic foci, using the newly developed tools, should be sufficient to prevent any future resurgence.
Topics: Animals; Humans; Trypanosomiasis, African; Tsetse Flies; Uganda
PubMed: 35942856
DOI: 10.1097/QCO.0000000000000860 -
PLoS Neglected Tropical Diseases Dec 2016Control operations targeting Animal African Trypanosomiasis and its primary vector, the tsetse, were covering approximately 128,000 km2 of Africa in 2001, which is a... (Review)
Review
BACKGROUND
Control operations targeting Animal African Trypanosomiasis and its primary vector, the tsetse, were covering approximately 128,000 km2 of Africa in 2001, which is a mere 1.3% of the tsetse infested area. Although extensive trypanosomiasis and tsetse (T&T) control operations have been running since the beginning of the 20th century, Animal African Trypanosomiasis is still a major constraint of livestock production in sub-Saharan Africa.
METHODOLOGY/PRINCIPAL FINDINGS
We performed a systematic review of the existing literature describing T&T control programmes conducted in a selection of five African countries, namely Burkina Faso, Cameroon, Ethiopia, Uganda and Zambia, between 1980 and 2015. Sixty-eight documents were eventually selected from those identified by the database search. This was supplemented with information gathered through semi-structured interviews conducted with twelve key informants recruited in the study countries and selected based on their experience and knowledge of T&T control. The combined information from these two sources was used to describe the inputs, processes and outcomes from 23 major T&T control programmes implemented in the study countries. Although there were some data gaps, involvement of the target communities and sustainability of the control activities were identified as the two main issues faced by these programmes. Further, there was a lack of evaluation of these control programmes, as well as a lack of a standardised methodology to conduct such evaluations.
CONCLUSIONS/SIGNIFICANCE
Past experiences demonstrated that coordinated and sustained control activities require careful planning, and evidence of successes, failures and setbacks from past control programmes represent a mine of information. As there is a lack of evaluation of these programmes, these data have not been fully exploited for the design, analyses and justification of future control programmes.
Topics: Animals; Burkina Faso; Cameroon; Ethiopia; Insect Control; Trypanosomiasis, African; Tsetse Flies; Uganda; Zambia
PubMed: 28027299
DOI: 10.1371/journal.pntd.0005247 -
ELife Sep 2021The parasite that causes African sleeping sickness can be transmitted from mammals to tsetse flies in two stages of its lifecycle, rather than one as was previously...
The parasite that causes African sleeping sickness can be transmitted from mammals to tsetse flies in two stages of its lifecycle, rather than one as was previously thought.
Topics: Animals; Life Cycle Stages; Trypanosomiasis, African; Tsetse Flies
PubMed: 34534076
DOI: 10.7554/eLife.72980