This review focuses on the most reliable and up-to-date methods for diagnosing trypanosomoses, a group of diseases of wild and domestic mammals, caused by trypanosomes, parasitic zooflagellate ...protozoans mainly transmitted by insects. In Africa, the Americas and Asia, these diseases, which in some cases affect humans, result in significant illness in animals and cause major economic losses in livestock. A number of pathogens are described in this review, including several Salivarian trypanosomes, such as Trypanosoma brucei sspp. (among which are the agents of sleeping sickness, the human African trypanosomiasis HAT), Trypanosoma congolense and Trypanosoma vivax (causing "Nagana" or animal African trypanosomosis AAT), Trypanosoma evansi ("Surra") and Trypanosoma equiperdum ("Dourine"), and Trypanosoma cruzi, a Stercorarian trypanosome, etiological agent of the American trypanosomiasis (Chagas disease). Diagnostic methods for detecting zoonotic trypanosomes causing Chagas disease and HAT in animals, as well as a diagnostic method for detecting animal trypanosomes in humans (the so-called "atypical human infections by animal trypanosomes" a-HT), including T. evansi and Trypanosoma lewisi (a rat parasite), are also reviewed. Our goal is to present an integrated view of the various diagnostic methods and techniques, including those for: (i) parasite detection; (ii) DNA detection; and (iii) antibody detection. The discussion covers various other factors that need to be considered, such as the sensitivity and specificity of the various diagnostic methods, critical cross-reactions that may be expected among Trypanosomatidae, additional complementary information, such as clinical observations and epizootiological context, scale of study and logistic and cost constraints. The suitability of examining multiple specimens and samples using several techniques is discussed, as well as risks to technicians, in the context of specific geographical regions and settings. This overview also addresses the challenge of diagnosing mixed infections with different Trypanosoma species and/or kinetoplastid parasites. Improving and strengthening procedures for diagnosing animal trypanosomoses throughout the world will result in a better control of infections and will significantly impact on "One Health," by advancing and preserving animal, human and environmental health.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Trypanosoma brucei causes human African trypanosomiasis (HAT). Three subspecies were described: T. b. gambiense (Tbg) and T. b. rhodesiense (Tbr) in humans, and T. b. brucei (Tbb) in animals. ...Molecular markers subdivided Tbg into two groups: Tbg1 and Tbg2, of which the latter is different from Tbg1 and Tbr (absence of the SRA gene), but indistinguishable from Tbb. Tbg2 is considered to be a zoonotic form of HAT in West Africa. Tbg2 was found mainly in Côte d'Ivoire between 1978 and 1992, but the latest description was made in Ghana in 2013. New molecular tools would be welcome to characterize such infections and determine their origins (resistance to human serum or patient immunodeficiency) in the current context of HAT elimination.
Tbg2 was defined as all human-infective T. brucei trypanosomes from West and Central Africa that do not fit into the category Tbg1. Tbg2 is genetically heterogeneous, and differs from Tbg1 when using various molecular markers.Tbg2 is also genetically different from Tbr, with a consistent lack of the serum-resistance-associated gene in those strains that were tested. Tbg2, Tbb, and Tbr are highly diverse lineages that remain to be investigated more thoroughly.Tbg2 was found mainly in Côte d'Ivoire between 1978 and 1992, but the latest descriptions of Tbg2 were made in Ghana in 2003 and 2013. No other record could be found between 1992 and 2003.Tbg2 represents a zoonotic form of HAT. Human infectivity probably arose multiple times and so could do so again. In the elimination context, it is crucial to detect such infections and determine their origins (resistance to human serum or patient immunodeficiency).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Reliable diagnostic tools are needed to choose the appropriate treatment and proper control measures for animal trypanosomoses, some of which are pathogenic. Trypanosoma cruzi, for example, is ...responsible for Chagas disease in Latin America. Similarly, pathogenic animal trypanosomoses of African origin (ATAO), including a variety of Trypanosoma species and subspecies, are currently found in Africa, Latin America and Asia. ATAO limit global livestock productivity and impact food security and the welfare of domestic animals. This review focusses on implementing previously reviewed diagnostic methods, in a complex epizootiological scenario, by critically assessing diagnostic results at the individual or herd level. In most cases, a single diagnostic method applied at a given time does not unequivocally identify the various parasitological and disease statuses of a host. These include "non-infected", "asymptomatic carrier", "sick infected", "cured/not cured" and/or "multi-infected". The diversity of hosts affected by these animal trypanosomoses and their vectors (or other routes of transmission) is such that integrative, diachronic approaches are needed that combine: (i) parasite detection, (ii) DNA, RNA or antigen detection and (iii) antibody detection, along with epizootiological information. The specificity of antibody detection tests is restricted to the genus or subgenus due to cross-reactivity with other Trypanosoma spp. and Trypanosomatidae, but sensitivity is high. The DNA-based methods implemented over the last three decades have yielded higher specificity and sensitivity for active infection detection in hosts and vectors. However, no single diagnostic method can detect all active infections and/or trypanosome species or subspecies. The proposed integrative approach will improve the prevention, surveillance and monitoring of animal trypanosomoses with the available diagnostic tools. However, further developments are required to address specific gaps in diagnostic methods and the sustainable control or elimination of these diseases.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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•Trypanosoma rangeli and Trypanosoma cruzi are distant species convergently adapted to humans.•Trypanosoma rangeli is closely related to Old Word trypanosomes of bats, civets, rats ...and monkeys.•A bat trypanosome transmitted by cimicids was the origin of T. rangeli and T. cruzi.•Bat trypanosomes can jump to a range of new hosts including monkeys and humans.
Trypanosoma rangeli and Trypanosoma cruzi are generalist trypanosomes sharing a wide range of mammalian hosts; they are transmitted by triatomine bugs, and are the only trypanosomes infecting humans in the Neotropics. Their origins, phylogenetic relationships, and emergence as human parasites have long been subjects of interest. In the present study, taxon-rich analyses (20 trypanosome species from bats and terrestrial mammals) using ssrRNA, glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH), heat shock protein-70 (HSP70) and Spliced Leader RNA sequences, and multilocus phylogenetic analyses using 11 single copy genes from 15 selected trypanosomes, provide increased resolution of relationships between species and clades, strongly supporting two main sister lineages: lineage Schizotrypanum, comprising T. cruzi and bat-restricted trypanosomes, and TraTve-Tco formed by T. rangeli, Trypanosoma vespertilionis and Trypanosoma conorhini clades. Tve comprises European T. vespertilionis and African T. vespertilionis-like of bats and bat cimicids characterised in the present study and Trypanosoma sp. Hoch reported in monkeys and herein detected in bats. Tco included the triatomine-transmitted tropicopolitan T. conorhini from rats and the African NanDoum1 trypanosome of civet (carnivore). Consistent with their very close relationships, TraTve-Tco species shared highly similar Spliced Leader RNA structures that were highly divergent from those of Schizotrypanum. In a plausible evolutionary scenario, a bat trypanosome transmitted by cimicids gave origin to the deeply rooted TraTve-Tco and Schizotrypanum lineages, and bat trypanosomes of diverse genetic backgrounds jumped to new hosts. A long and independent evolutionary history of T. rangeli more related to Old World trypanosomes from bats, rats, monkeys and civets than to Schizotrypanum spp., and the adaptation of these distantly related trypanosomes to different niches of shared mammals and vectors, is consistent with the marked differences in transmission routes, life-cycles and host-parasite interactions, resulting in T. cruzi (but not T. rangeli) being pathogenic to humans.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK, ZRSKP
Beside typical human trypanosomes responsible of sleeping sickness in Africa and Chagas disease in Latin America, there is a growing number of reported atypical human infections due to Trypanosoma ...evansi, a livestock parasite, or Trypanosoma lewisi, a rat parasite, especially in Asia. Drugs available for the treatment of T. brucei ssp. in humans are obviously of choice for the control of T. evansi because it is derived from T. brucei. However, concerning T. lewisi, there is an urgent need to determine the efficacy of trypanocidal drugs for the treatment in humans. In a recent study, pentamidine and fexinidazole were shown to have the best efficacy against one stock of T. lewisi in rats.
In the present study suramin, pentamidine, eflornitine, nifurtimox, benznidazole and fexinidazole, were evaluated at low and high doses, in single day administration to normal rats experimentally infected with a stock of T. lewisi recently isolated in Thailand. Because none of these treatments was efficient, a trial was made with the most promising trypanocide identified in a previous study, fexinidazole 100mg/kg, in 5 daily administrations. Results observed were unclear. To confirm the efficacy of fexinidazole, a mixed infection protocol was set up in cyclophosphamide immunosuppressed rats. Animals were infected successively by T. lewisi and T. evansi, and received 10 daily PO administrations of 200mg/kg fexinidazole. Drastic effects were observed against T. evansi which was cleared from the rat's blood within 24 to 48h; however, the treatment did not affect T. lewisi which remained in high number in the blood until the end of the experiment. This mixed infection/treatment protocol clearly demonstrated the efficacy of fexinidazole against T. evansi and its inefficacy against T. lewisi. Since animal trypanocides were also recently shown to be inefficient, other protocols as well as other T. lewisi stocks should be investigated in further studies.
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•There is an increasing number of clinical reports of T. lewisi infections in humans.•The 6 human trypanocidal drugs used were unable to cure T. lewisi infected rats•In rats infected by T. lewisi and T. evansi, fexinidazole treatment cured T. evansi only.•So far no human trypanocidal drug proved to be efficient against T. lewisi in rats.•Further investigations are needed to identify efficient drugs for the control of T. lewisi in humans.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK, ZRSKP
We report an Indian farmer who had fluctuating trypanosome parasitemia associated with febrile episodes for five months. Morphologic examination of the parasites indicated the presence of large ...numbers of trypanosomes belonging to the species Trypanosoma evansi, which is normally a causative agent of animal trypanosomiasis known as surra. Basic clinical and biologic examinations are described, using several assays, including parasitologic, serologic, and molecular biologic tests, all of which confirmed the infecting species as T. evansi. Analysis of cerebrospinal fluid indicated no invasion of the central nervous system (CNS) by trypanosomes. Suramin, a drug used exclusively for treatment of early-stage human African trypanosomiasis with no CNS involvement, effected apparent cure in the patient. This is the first case reported of human infection due to Trypanosoma evansi, which was probably caused by transmission of blood from an infected animal.
A growing number of atypical human infections due to the livestock parasite Trypanosoma evansi, or to the rat parasite Trypanosoma lewisi, are reported in humans in Asia. In some cases, clinical ...evolutions request treatments, however, so far, there were very few attempts to control T. lewisi using trypanocidal drugs. In a study published elsewhere, the efficacy of human trypanocides is evaluated in laboratory rats, and it concludes that none of them is able to cure rats experimentally infected with T. lewisi. Control of T. lewisi in rat would be a step for identification of drugs against this parasite. In the present study, 4 veterinary drugs: diminazene aceturate, isometamidium chloride, melarsomine hydrochloride and quinapyramine sulfate and chloride, were evaluated at low and high doses, in intra-muscular injections to normal rats experimentally infected with a stock of T. lewisi from Thailand. None of these treatments being efficient, a trial was also made using melarsomine hydrochloride in T. evansi infected rats and in mixed T. lewisi and T. evansi infected rats, in order to demonstrate the efficacy of the drugs under the present protocol. T. evansi was cleared from the rat's blood the day after the treatment, while, T. lewisi remained unaffected until the end of the experiment. These observations clearly demonstrated the efficacy of melarsomine hydrochloride against T. evansi and its inefficacy against T. lewisi. In conclusion none of the veterinary drugs was efficient against this stock of T. lewisi. Other protocols using higher doses or other drugs and T. lewisi stocks should be investigated in further studies. The control of T. lewisi infection in Wistar rats, using veterinary trypanocidal drugs, remains so far unsuccessful.
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•There is an increasing number of clinical reports of Trypanosoma lewisi infections in humans.•The 4 veterinary trypanocidal drugs used were unable to cure T. lewisi infected rats.•In rats infected by T. lewisi and Trypanosoma evansi, melarsomine hydrochloride cured T. evansi only.•No veterinary trypanocidal drug proved to be efficient against T. lewisi in rats.•Further investigations are needed to identify efficient drugs for T. lewisi control in humans.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK, ZRSKP
This paper reports the first evidence of the presence of bacteria, other than the three previously described as symbionts,
Wigglesworthia glossinidia,
Wolbachia, and
Sodalis glossinidius, in the ...midgut of
Glossina palpalis palpalis, the tsetse fly, a vector of the chronic form of human African trypanosomiasis in sub-Saharan African countries. Based on the morphological, nutritional, physiological, and phylogenetic results, we identified
Enterobacter,
Enterococcus, and
Acinetobacter spp. as inhabitants of the midgut of the tsetse fly from Angola.
Enterobacter spp. was the most frequently isolated. The role of these bacteria in the gut, in terms of vector competence of the tsetse fly, is discussed, as is the possibility of using these bacteria to produce
in situ trypanolytic molecules.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
African trypanosomosis is a major threat to livestock production in sub-Saharan Africa. Although the disease mainly concerns cattle, dogs can also be infected by Trypanosoma spp. transmitted by ...tsetse flies. Between 1997 and 2003, the parasite Trypanosoma congolense was identified in French military dogs sent to Africa. On infected dogs, the diagnosis was made during the mission or just after the return to France, depending on when the symptoms appeared. The high incidence and mortality rate among these dogs led veterinarians of the French Health Service to implement a systematic chemoprophylaxis beginning in 2004. Between 2004 and 2011, the chemoprophylaxis was carried out on more than 400 military dogs. The protocol of chemoprophylaxis relies on the use of isometamidium chloride (Trypamidium®, Merial). The drug has been used successfully at the dosage of 1mg/kg body weight by deep intramuscular injection, every two or three months. In addition, dogs are given collars impregnated with deltamethrin (Scalibor®, MSD Animal Health). Isometamidium chloride was also used successfully in the treatment of military dogs infected with T. congolense, with a full recovery and without any relapses.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
Although clearly demonstrated in Trypanosoma brucei , genetic exchange remains controversial in other trypanosome species. Recently, Morrison and co-workers applied a population-genetics analysis, ...and established the existence of mating in Trypanosoma congolense . Starting from this original discovery, we focus here on the important question of how mating is induced during the trypanosome life cycle and discuss the use of statistics to evidence this type of non-obligatory biological process.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK