Trypanosome Infection Research Articles

A Systematic Review on Dourine (Equine Trypanosomiasis)

Dourine is a chronic infectious disease that affects breeding horses and spreads from animal to animal during coitus. Trypanosoma equiperdum is the causal agent in this case. Both infected males and females have vaginal discharges that contain these protozoa. Trypanosoma equiperdum is mostly found in tissue and is rarely seen in blood, in contrast to other Trypanosoma species. Dourine is the only biological vector capable of dispersing the Trypanosoma infection, as there are no other viable options. Sometimes the disease is passed on to foals by tainted milk or colostrum meal. Primarily, dourine affects mules, horses, and donkeys. However, donkeys and mules are more resilient than horses and could still be employed as covert messengers in the future. The primary symptoms of the illness are vaginal edema, cutaneous plaques, neurological symptoms, and persistent malnourishment. Identification of the parasite and detection of clinical symptoms are prerequisites for making a diagnosis. Horses from locations where the disease is endemic should not be brought in to prevent its spread to areas where it is not present. Not much research has been done on the condition, especially in developing countries where there is a lack of understanding about it, although it has a significant and asymptomatic influence on an animal’s health. Therefore, the objective of this review is to review Dourine (equine trypanosomiasis).

A METHOD FOR ISOLATING AND SEQUENCING TRYPANOSOME CELLS TO INVESTIGATE SPECIES ASSOCIATIONS IN MULTIPLE MORPHOTYPE INFECTIONS.

Trypanosome infections containing multiple morphologies have been described from all classes of vertebrates, including mammals, birds, non-avian reptiles, amphibians, and fish. These mixed infections make it challenging to evaluate trypanosome diversity, as it is not immediately clear whether the forms present in the bloodstream represent different species or a single pleomorphic species. Amphibians are common hosts for trypanosomes and are often infected by multiple trypanosome morphologies in the bloodstream. Based on morphological observations and life cycle studies, many authors have considered multiple trypanosome morphotypes found infecting the same frogs to be a single pleomorphic species. However, molecular evidence supporting pleomorphic trypanosome species in amphibians is lacking, primarily because linking sequence data to bloodstream trypanosome morphology in mixed infections is extremely challenging. Here we present methods to isolate individual trypanosome cells of 6 morphotypes from frog blood for nested PCR of the 18S rRNA and gGAPDH genes. Single trypanosome cells were isolated by dilution and 3 DNA extraction methods, and 5 nested PCR primer regimes were utilized to optimize amplification from very low starting concentrations. The success rates of extraction methods ranged from 29 to 50% with the use of a Direct PCR kit having the highest success rate. Although the success rate varied in the different combinations of extraction methods and primer regimes, multiple individuals of all 6 trypanosome morphotypes were sequenced for both genes in a novel way that links sequence data to cell morphology by observing isolated cells with a microscope before PCR amplification. All 6 morphologically distinguishable morphotypes coinfecting a frog were genetically distinct. The only other recent molecular study on amphibian trypanosomes also found genetic differences between morphotypes in multiple infections. Together these studies suggest that the occurrence of pleomorphism may be overestimated in amphibian trypanosomes. The methods presented here offer a promising solution to characterize trypanosome diversity within multiple morphotype infections.

Trypanosoma (Euglenozoa: Kinetoplastea) infections in rodents, bats, and shrews along an elevation and disturbance gradient in Central Sulawesi, Indonesia

Trypanosoma (Euglenozoa: Kinetoplastea) infections in rodents, bats, and shrews along an elevation and disturbance gradient in Central Sulawesi, Indonesia

In vitro trypanocidal potency and in vivo treatment efficacy of oligomeric ethylene glycol-tethered nitrofurantoin derivatives

African trypanosomiasis is a significant vector-borne disease of humans and animals in the tsetse fly belt of Africa, particularly affecting production animals such as cattle, and thus, hindering food security. Trypanosoma congolense (T. congolense), the causative agent of nagana, is livestock's most virulent trypanosome species. There is currently no vaccine against trypanosomiasis; its treatment relies solely on chemotherapy. However, pathogenic resistance has been established against trypanocidal agents in clinical use. This underscores the need to develop new therapeutics to curb trypanosomiasis. Many nitroheterocyclic drugs or compounds, including nitrofurantoin, possess antiparasitic activities in addition to their clinical use as antibiotics. The current study evaluated the in vitro trypanocidal potency and in vivo treatment efficacy of previously synthesized antileishmanial active oligomeric ethylene glycol derivatives of nitrofurantoin. The trypanocidal potency of analogues 2a-o varied among the trypanosome species; however, T. congolense strain IL3000 was more susceptible to these drug candidates than the other human and animal trypanosomes. The arylated analogues 2k (IC50 0.04 µM; SI >6365) and 2l (IC50 0.06 µM; SI 4133) featuring 4-chlorophenoxy and 4-nitrophenoxy moieties, respectively, were revealed as the most promising antitrypanosomal agents of all analogues against T. congolense strain IL3000 trypomastigotes with nanomolar activities. In a preliminary in vivo study involving T. congolense strain IL3000 infected BALB/c mice, the oral administration of 100 mg/kg/day of 2k caused prolonged survival up to 18 days post-infection relative to the infected but untreated control mice which survived 9 days post-infection. However, no cure was achieved due to its poor solubility in the in vivo testing medium, assumably leading to low oral bioavailability. These results confirm the importance of the physicochemical properties lipophilicity and water solubility in attaining not only in vitro trypanocidal potency but also in vivo treatment efficacy. Future work will focus on the chemical optimization of 2k through the investigation of analogues containing solubilizing groups at certain positions on the core structure to improve solubility in the in vivo testing medium which, in the current investigation, is the biggest stumbling block in successfully treating either animal or human Trypanosoma infections.

Impact of a small-scale tsetse fly control operation with deltamethrin impregnated "Tiny Targets" on tsetse density and trypanosomes' circulation in the Campo sleeping sickness focus of South Cameroon.

Significant progress has been made towards African sleeping sickness elimination in the last decade. Indeed, the World Health Organization (WHO) global goal of eliminating the chronic form of the disease as a public health problem was achieved in 2020 (i.e., < 2,000 new cases per year). Vector control has played an important role in achieving this goal. In this study, we evaluated the impact of the insecticide impregnated Tiny Targets on tsetse fly densities and their infection rates with Trypanosoma spp in the Campo sleeping sickness focus of South Cameroon. The study site was divided into two areas: (i) the south-west experimental area, which included vector control, and (ii) the eastern part as the non-intervention area. After compiling the baseline entomological data (tsetse densities and trypanosome infection rates), around 2000 Tiny Targets were deployed in the South-West area and replaced every six months for two years. Post-intervention surveys were conducted every six months to determine tsetse densities and levels of trypanosome infections with PCR-based methods. Following the intervention, tsetse mean catches decreased by 61% after six months, and up to 73% after twelve months (pre-intervention: 2.48 flies/trap/day, 95%CI [1.92-3.14]; 12-months post-intervention: 0.66 tsetse/trap/day, 95%CI [0.42-0.94]). This decrease was not sustained after 18 months, and the mean catch doubled compared to that after 12 months. After 24 months, the mean catches still increased by 17% (18 months: 1.45 tsetse/trap/day, 95%CI [1.07-1.90] and 24 months: 1.71 tsetse/trap/day, 95%CI [1.27-2.24]). In the non-intervention area, a variation in tsetse catches was observed during the two years, with a general increase from 2.43 [0.73-5.77] to 3.64 [1.47-7.70] tsetse/trap/day. In addition, trypanosome infection rates dropped by 75% in both areas (P-value < 0.001) from 21.20% to 5.06% and from 13.14% to 3.45% in intervention and control areas respectively. Tiny targets have proven useful in reducing tsetse population densities and trypanosome infection rates, providing evidence for the integration of this tool in current strategies towards trypanosomiasis elimination in Campo. The non-sustained decrease of tsetse densities after one year may indicate reinvasions from neighbouring breeding sites or that the intervention area was not large enough. Our results show the need to scale up by accessing difficult breeding sites and extend the tiny targets to the whole transborder focus.

Performance of diagnostic tests for Trypanosoma brucei brucei in experimentally infected pigs.

Animal African trypanosomosis is an important vector-borne disease of livestock in sub-Saharan Africa. Pigs seem relatively tolerant to trypanosome infection and could act as a reservoir of trypanosomes affecting animals and humans. Our ability to reliably detect trypanosome infection in pigs depends on the performance of diagnostic tools, which is not well known. In pigs experimentally infected with Trypanosoma brucei brucei, we evaluated the performance of parasitological Buffy Coat Technique (BCT), two molecular (TBR and 5.8S PCR) and four serological tests (CATT, HAT Sero-K-Set rapid diagnostic test-RDT, indirect ELISA, immune trypanolysis). Most diagnostic tests showed high specificity, estimated at 100% (95% CI = 74-100%) with the exception of CATT and RDT whose specificity varied between 100% (95% CI = 74-100%) to 50% (95% CI = 7-93%) during the experiment. The sensitivity of each test fluctuated over the course of the infection. The percentage of positive BCT over the infection (30%) was lower than of positive PCR (56% and 62%, depending on primers). Among the serological tests, the percentage of positive tests was 97%, 96%, 86% and 84% for RDT, ELISA, immune trypanolysis and CATT, respectively. Fair agreement was observed between both molecular tests (κ = 0.36). Among the serological tests, the agreement between the ELISA and the RDT was substantial (κ = 0.65). Our results on the T.b. brucei infection model suggest that serological techniques are efficient in detecting the chronic phase of infection, PCR is able to detect positive samples several months after parasites inoculation while BCT becomes negative. BCT examination and RDT are useful to get a quick information in the field, and BCT can be used for treatment decision. ELISA appears most suited for epidemiological studies. The selection of diagnostic tests for trypanosomosis in pigs depends on the context, the objectives and the available resources.

A smart economic way to control camel parasites and improve camel production in Egypt

Treatment of the parasites in camels strategically by administration of the specific drugs (Ivomec 1% SC injection, Amprolium hydrochloride orally, Naganol SC injection and Deltamethrin, poure on) at a specially selected time concerning the transmission season of Nematodes, Coccidia, Trypanosoma, Ticks & mite infection respectively causes relief to the animal from the stress of the parasite, minimizes the number of eggs shedding, and improves its general health conditions. However, the present study designed and applied three selected treatment regimes to 300 parasitically infected and controlled camels in Middle Egypt. The first regime was performed by treating animals two times/year during the peak of infection; the first was in April against internal parasites, and in July against external parasites. The second program was conducted by treating animals three times/year; the first was in March against early-arrived internal parasites, the second was in June against external and internal ones, and the third treatment was in August against the rest of the external parasites. Furthermore, the last suggested regime was applied by applying 4 treatments/year: the first was in February against the internal parasites, the second was in May against the early infection by external parasites as well as the remaining internal parasites, and the third was in July against the external parasite. The fourth treatment was in September to eradicate the remaining internal parasite and keep the animal parasite-free during winter.Treatment was applied to the whole flock; however, the movement of treated and control animals was restricted. The study proved a significant decrease in the incidence and level of parasite burden in animals that received 3 and 4 treatments/year, associated with marked improvement in the mean body score, blood parameters, and rate of pregnancy and its related hormones, as well as enhancement in liver and kidney function parameters. The selection of 3 or 4 treatment regimens will be evaluated concerning their economic cost and total income after another year after each protocol's end.

First investigation of blood parasites of bats in Burkina Faso detects Hepatocystis parasites and infections with diverse Trypanosoma spp.

Bats are hosts to a large diversity of eukaryotic protozoan blood parasites that comprise species of Trypanosoma and different haemosporidian parasite taxa and bats have played an important role in the evolutionary history of both parasite groups. However, bats in several geographical areas have not been investigated, including in Burkina Faso, where no information about malaria parasites and trypanosomes of bats exists to date.In this study, we collected data on the prevalence and the phylogenetic relationships of protozoan blood parasites in nine different bat species in Burkina Faso. Hepatocystis parasites were detected in two species of epauletted fruit bats, and a relatively high diversity of trypanosome parasites was identified in five bat species. The phylogenetic analyses recovered the trypanosome parasites of the bat species Rhinolophus alcyone and Nycteris hispida as close relatives of T. livingstonei, the trypanosome infections in Scotophilus leucogaster as closely related to the species T. vespertilionis and the trypanosomes from Pipistrellus nanulus and Epomophorus gambianus might present the species T. dionisii. These findings of the first investigation in Burkina Faso present a first snapshot of the diversity of protozoan blood parasites in bats in this country.

Comparative biochemical changes induced by experimental infection of &lt;i&gt;Trypanosoma congolense&lt;/i&gt; and &lt;i&gt;Trypanosoma brucei&lt;/i&gt; in West African Dwarf (WAD) sheep

Trypanosomosis is still a major impediment to livestock production in most tropical environments despite various efforts geared towards eradicating the disease. Small ruminants are known to be fully susceptible to pathogenic trypanosome infections, however, studies in small ruminants are still scanty compared to large ruminants. Comparative pathogenicity and biochemical changes in twenty West African Dwarf (WAD) sheep aged between 8-10 months were investigated. Sheep were randomly assigned into groups A and B and experimentally infected with either Trypanosoma congolense or Trypanosoma brucei. Both species of trypanosomes caused significant but varying degrees of alterations in the biochemical parameters studied. There was a consistent and significant increase (P&lt;0.05) in the levels of total proteins, globulin, fibrinogen, urea, creatinine, sodium, bicarbonate, inorganic phosphate and chloride from day 21 post infection in both groups, and these were sustained till the experiment was terminated. Similarly, the levels of albumin, cholesterol and albumin/globulin ratio progressively decreased (p&lt;0.05) post infection starting from day 28, whereas potassium levels remained unchanged throughout post-infection period. There was a strong positive correlation between total protein and urea in groups A and B (r = 0.937 and r = 0.908), respectively as well as between total protein and creatinine in groups A and B (r = 0.937 and r = 0.908), respectively. Generally, significantly higher biochemical alterations (p&lt;0.05) in T. congolenseinfectedsheep. It can thus be concluded that trypanosome infection in sheep could lead to significant pathological and functional disorders in vital organs including liver and kidney which may have resulted in the biochemical alterations observed; these being influenced by individual trypanosome species.

Diversity of trypanosome species in small ruminants, dogs and pigs from three sleeping sickness foci of the south of Chad.

Despite considerable data generated on livestock trypanosomoses in tsetse-infested areas, little attention was paid for animal African trypanosomosis (AAT) in sleeping sickness foci. This study aimed to fill this gap by determining the diversity and prevalence of trypanosome species in animals from three Chadian human African trypanosomosis (HAT) foci. Blood samples were collected from 443 goats, 339 sheep, 228 dogs and 98 pigs of the Mandoul, Maro and Moissala HAT foci in the south of Chad. Capillary tube centrifugation (CTC) and specific primers were used to search trypanosomes. The prevalence of trypanosome infections was 6.3% for CTC and 22.7% for PCR. Trypanosomes of the sub-genus Trypanozoon had the highest prevalence (16.6%) while T. congolense savannah (1.9%) was least prevalent. Significant differences were recorded between the prevalence of trypanosome species (χ2 = 8.34; p = 0.04) and HAT foci (χ2 = 24.86; p ≤0.0001). Maro had the highest prevalence (32.7%) and Mandoul the lowest (17.4%). Significant differences were also recorded for T. congolense forest (χ2 = 45.106; p < 0.0001) and all T. congolense (χ2 = 34.992; p < 0.0001). Goats had the highest prevalence (26.9%) and sheep the lowest one (18.6%). Between animals, significant differences were recorded for trypanosome of the sub-genus Trypanozoon (χ2 = 9.443; p = 0.024), T. congolense forest (χ2 = 10.476; p = 0.015) and all T. congolense (χ2 = 12.152; p = 0.007). Of the 251 animals carrying trypanosome infections, 88.8% had single infections while 11.2% had more than one trypanosome species. The overall prevalence of single and mixed trypanosome infections were respectively 20.1% and 2.6% in animal taxa from of all foci. This study highlighted a diversity of trypanosomes in animal taxa of all HAT foci. It showed that AAT constitutes a threat for animal health and animal breeding in Chadian HAT foci. In these tsetse infested areas, reaching the elimination of AAT requires the designing and the implementation of control measures against trypanosome infections.

Genomic evidence of sex chromosome aneuploidy and infection-associated genotypes in the tsetse fly Glossina fuscipes, the major vector of African trypanosomiasis in Uganda.

The primary vector of the trypanosome parasite causing human and animal African trypanosomiasis in Uganda is the riverine tsetse fly Glossina fuscipes fuscipes (Gff). Our study improved the Gff genome assembly with whole genome 10× Chromium sequencing of a lab reared pupae, identified autosomal versus sex-chromosomal regions of the genome with ddRAD-seq data from 627 field caught Gff, and identified SNPs associated with trypanosome infection with genome-wide association (GWA) analysis in a subset of 351 flies. Results from 10× Chromium sequencing greatly improved Gff genome assembly metrics and assigned a full third of the genome to the sex chromosome. Results from ddRAD-seq suggested possible sex-chromosome aneuploidy in Gff and identified a single autosomal SNP to be highly associated with trypanosome infection. The top associated SNP was ∼1100bp upstream of the gene lecithin cholesterol acyltransferase (LCAT), an important component of the molecular pathway that initiates trypanosome lysis and protection in mammals. Results suggest that there may be naturally occurring genetic variation in Gff in genomic regions in linkage disequilibrium with LCAT that can protect against trypanosome infection, thereby paving the way for targeted research into novel vector control strategies that can promote parasite resistance in natural populations.

γδ T cells control murine skin inflammation and subcutaneous adipose wasting during chronic Trypanosoma brucei infection

African trypanosomes colonise the skin to ensure parasite transmission. However, how the skin responds to trypanosome infection remains unresolved. Here, we investigate the local immune response of the skin in a murine model of infection using spatial and single cell transcriptomics. We detect expansion of dermal IL-17A-producing Vγ6+ cells during infection, which occurs in the subcutaneous adipose tissue. In silico cell-cell communication analysis suggests that subcutaneous interstitial preadipocytes trigger T cell activation via Cd40 and Tnfsf18 signalling, amongst others. In vivo, we observe that female mice deficient for IL-17A-producing Vγ6+ cells show extensive inflammation and limit subcutaneous adipose tissue wasting, independently of parasite burden. Based on these observations, we propose that subcutaneous adipocytes and Vγ6+ cells act in concert to limit skin inflammation and adipose tissue wasting. These studies provide new insights into the role of γδ T cell and subcutaneous adipocytes as homeostatic regulators of skin immunity during chronic infection.

Prevalence of blood and skin trypanosomes in domestic and wild fauna from two sleeping sickness foci in Southern Cameroon.

Although studies on African Trypanosomiases revealed a variety of trypanosome species in the blood of various animal taxa, animal reservoirs of Trypanosoma brucei gambiense and anatomical niches such as skin have been overlooked in most epidemiological settings. This study aims to update epidemiological data on trypanosome infections in animals from human African trypanosomiasis (HAT) foci of Cameroon. Blood and skin snips were collected from 291 domestic and wild animals. DNA was extracted from blood and skin snips and molecular approaches were used to identify different trypanosomes species. Immunohistochemical analyses were used to confirm trypanosome infections in skin snips. PCR revealed 137 animals (47.1%) with at least one trypanosome species in the blood and/or in the skin. Of these 137 animals, 90 (65.7%) and 32 (23.4%) had trypanosome infections respectively in the blood and skin. Fifteen (10.9%) animals had trypanosome infections in both blood and skin snip. Animals from the Campo HAT focus (55.0%) were significantly (X2 = 17.6; P< 0.0001) more infected than those (29.7%) from Bipindi. Trypanosomes of the subgenus Trypanozoon were present in 27.8% of animals while T. vivax, T. congolense forest type and savannah type were detected in 16.5%, 10.3% and 1.4% of animals respectively. Trypanosoma b. gambiense infections were detected in the blood of 7.6% (22/291) of animals. No T. b. gambiense infection was detected in skin. This study highlights the presence of several trypanosome species in the blood and skin of various wild and domestic animals. Skin appeared as an anatomical reservoir for trypanosomes in animals. Despite methodological limitations, pigs, sheep, goats and wild animals were confirmed as potential reservoirs of T. b. gambiense. These animal reservoirs must be considered for the designing of control strategies that will lead to sustainable elimination of HAT.

Molecular and hematological investigation of Trypanosoma evansi infection in Iranian one-humped camels (Camelus dromedarius).

Trypanosoma species cause animal trypanosomiasis that infects many animals. Trypanosoma evansi is an organism that infects camels. There are many economic problems associated with this disease, including lower milk and meat yields and abortions. The purpose of the current survey was molecular study of the presence of Trypanosoma in dromedary camel blood in the south of Iran, and its effects on the hematologic, and some acute-phase protein changes. Blood samples were aseptically collected from the jugular vein of dromedary camels (n = 100; aged from 1 to 6years) originating from Fars Province in EDTA-coated vacutainers. Genomic DNA from 100 µL of the whole blood was extracted and amplified using a PCR assay based on ITS1, 5.8S, and ITS2 ribosomal regions. Also, the PCR products obtained were sequenced. Moreover, the changes in hematological parameters and serum acute-phase proteins (serum amyloid A, alpha-1 acid glycoprotein, and haptoglobin) were measured. Among 100 tested blood, nine samples (9%, 95% CI: 4.2-16.4%) were found positive by the PCR assay. The phylogenetic tree and blast analysis showed four different genotypes closely related to the strains (accession numbers: JN896754 and JN896755) previously reported from dromedary camels in Yazd Province, center Iran. Based on hematological analysis, normocytic and normochromic anemia and lymphocytosis were detected in the PCR-positive cases compared with the negative group. Furthermore, alpha-1 acid glycoprotein was significantly increased in the positive cases. There was a substantial and positive relation between the number of lymphocytes, and the levels of alpha-1 acid glycoprotein and serum amyloid A in the blood (p = 0.045, r = 0.223 and p = 0.036, r = 0.234, respectively). A noticeable frequency of T. evansi infection was reported in dromedary camels in south Iran. This is the first report on the genetic diversity of T. evansi in this region. There was a significant association among Trypanosoma infection, lymphocytosis, and alpha-1 acid glycoprotein. Trypanosoma-positive camels had a significant decrease in hematocrit (HCT), hemoglobin (Hb), and red blood cell (RBC) values compared to the non-infected group. Further experimental studies are needed to elucidate the hematological and acute-phase protein alteration during a different phase of Trypanosoma spp. infection.

Comparative pathogenicity of single and mixed drug-resistant Trypanosoma brucei brucei and Trypanosoma congolense infections in rats

Drug-resistant trypanosomes are widespread in sub-Saharan Africa and in conjunction with the drug-sensitive phenotypes cause a serious endemic wasting disease in animals. We evaluated the pathogenicity of single and mixed drug-resistant Trypanosoma brucei brucei and T. congolense isolates in 35 female rats, randomly divided into seven groups (1–7) of five rats. Group 1 was the uninfected control. Groups 2 and 3 were infected with drug-sensitive T. brucei brucei and T. congolense, respectively, whereas groups 4 and 5 were infected with multidrug-resistant T. brucei brucei and T. congolense respectively. Group 6 were infected with drug-sensitive T. brucei brucei and T. congolense while group 7 were infected with multidrug-resistant T. brucei brucei and T. congolense. Parasitaemia kinetics, haematological parameters, body weight, clinical signs, survival time, gross and histopathological changes in the spleen were evaluated. Parasitaemia occurred between day 3–9 post-infection in all the infected groups. Rats in groups 4 and 7 had markedly prolonged (p < 0.05) pre-patent period, days to first peak parasitaemia, survival time, and lower (p < 0.05) parasitaemia level than groups 2 and 6 rats while these parameters were comparable for groups 3 and 5 rats. Anaemia was noted in the infected groups but the severity did not vary amongst the infected groups. Severe clinical signs and splenic lesions were noted in rats infected with drug-sensitive trypanosome species compared to the multidrug-resistant species. Therefore, we conclude that the trypanosome isolates were pathogenic. However, the drug-sensitive T. brucei brucei and mixed drug-sensitive trypanosome infections were more pathogenic than their multidrug-resistant counterparts.

Trypanosomal Infection Rates in Glossina pallidipes in Bilbo village, Kamba District, Southern Ethiopia

This study was a cross-sectional study conducted at Bilbo village in Kamba district, Southwestern Ethiopia, from November 2018 to April 2019 with the aim of determining the infection rate of trypanosomes in Glossina pallidipes. A total of 384 Glossina pallidipes were captured using acetone and animal urine-baited NGU bi-conical and sticky traps. Their organs (proboscis, salivary gland, and midgut) were dissected and microscopically examined. About 53.39% of Glossina pallidipes were captured through NGU, and the remaining 29.17% and 17.45% were captured via bi-conical and sticky traps, respectively. Out of the dissected specimens, 131 (34.1%) Glossina pallidipes were found positive for trypanosomes. Of this, 109 (28.38%) and 22 (5.73%) were female and male tsetse flies, respectively. The highest proportion of the tsetse fly (19.27%) was infected by T. vivax, followed by T. congolense, and T. brucei. There was a statistically significant difference in trypanosome infection rate among the sex (P = 0.001) and age (P = 0.0024) categories of Glossina pallidipes. The presence of Glossina pallidipes positive for trypanosomes might have contributed to bovine trypanosomosis in the study area. Hence, further studies should be undertaken in order to categorically prioritize the control of tsetse flies in the study area. Keywords: Glossina pallidipes, T. brucei, T. congolense, T. vivax, traps, trypanosome infection rate

Cyanotriazoles are selective topoisomerase II poisons that rapidly cure trypanosome infections.

Millions who live in Latin America and sub-Saharan Africa are at risk of trypanosomatid infections, which cause Chagas disease and human African trypanosomiasis (HAT). Improved HAT treatments are available, but Chagas disease therapies rely on two nitroheterocycles, which suffer from lengthy drug regimens and safety concerns that cause frequent treatment discontinuation. We performed phenotypic screening against trypanosomes and identified a class of cyanotriazoles (CTs) with potent trypanocidal activity both in vitro and in mouse models of Chagas disease and HAT. Cryo-electron microscopy approaches confirmed that CT compounds acted through selective, irreversible inhibition of trypanosomal topoisomerase II by stabilizing double-stranded DNA:enzyme cleavage complexes. These findings suggest a potential approach toward successful therapeutics for the treatment of Chagas disease.

Molecular identification of trypanosoma species infecting dogs in nigeria by analysis of partial internal transcribed spacer-1 of RRNA gene

Trypanosomosis is becoming a major health challenge to dogs in the sub-Sahara Africa including Nigeria, but minimal reports are available on the molecular characteristic of trypanosomes infecting dogs in Nigeria. We characterized trypanosomes detected in naturally infected dogs by PCR and sequences analysis of the partial region of the trypanosomes internal transcribed spacer-1of ribosomal RNA (ITS1 rRNA). Animals presented to the University of Nigeria Veterinary Teaching Hospital (UNVTH) in Nsukka, Nigeria for examination and treatment were sampled for laboratory tests. DNA was extracted from 21 blood samples obtained from dogs that were confirmed positive for trypanosome infection by microscopy. ITS-1 was PCR amplified and sequenced bi-directionally. Sixteen samples have good bands, though one of them had unreadable sequence. Analyses of the sequence data by BLAST search on NCBI identified T. congolense, T. brucei gambiense, and T. evansi in 4.8, 4.8, and 91.4%, respectively, from the analysed samples from the infected dogs. Although the top BLAST hits for T. brucei group were due to T. evansi and T. b. gambiense, there is not enough discriminatory power in ITS-1 to distinguish subspecies. The aligned sequences of the trypanozoon were less polymorphic. Phylogenetic trees inferred by unweighted pair group method with arithmetic mean (UPGMA) algorithms separated trypanozoon group from the T. congolense into two distinct clades. In conclusion, this study suggests that the trypanozoon group of trypanosomes cause more canine trypanosomosis in the study area and suggests inclusion of dogs in strategic planning for control and eradication of trypanosomosis in sub-Sahara African countries.

Clinical and hemato-biochemical profiles of dogs diagnosed of natural trypanosomosis at university of Nigeria Veterinary Teaching Hospital, Nsukka

Hematological and serum biochemical profiles of animals are reflections of physiological disposition to their health status and production potentials. Findings in experimental studies on trypanosomosis may not translate directly to the expected findings in natural infections because of the effect of some variables like species and infecting dose of the parasite, nutritional status of the animal, concurrent infections, and stage of the trypanosomosis at the time of presentation to the clinic. Trypanosoma brucei and T. congolense infections in dogs have grave prognosis especially if the cases are not detected at their early stages. Clinical presentation, survivability of dogs treated with Diminazene aceturate as well as haematological and serum biochemical aberrations caused by natural infections with different Trypanosoma species were investigated with the view to identifying a variable or factor that could be used for prognostic evaluation in the treated dogs. Telephone numbers of the clients for dogs diagnosed with and treated against natural trypanosomes infections were collected and used to monitor the therapeutic outcomes. The clinical signs observed suggestive of late stage trypanosomosis were matched with the revelations from the case history. Significant (p ≤ 0.05) reductions in PCV, HB, absolute neutrophil, and significant (p ≤ 0.05) increase in monocytes count, serum urea, and creatinine were recorded in trypanosome infected dogs. Inability of clients to note the early clinical signs of infections with trypanosomes could have contributed to the low survival rate of the trypanosome-infected dogs even when treated.

Development of novel PEX5-PEX14 protein-protein interaction (PPI) inhibitors based on an oxopiperazine template

Protein-protein interactions (PPIs) constitute an important but challenging class of molecular targets for small molecules. The PEX5-PEX14 PPI has been shown to play a critical role in glycosome biogenesis and its disruption impairs the metabolism in Trpanosoma parasites, eventually leading to their death. Therefore, this PPI is a potential molecular target for new drugs against diseases caused by Trypanosoma infections. Here, we report a new class of peptidomimetic scaffolds to target the PEX5-PEX14 PPI. The molecular design was based on an oxopiperazine template for the α-helical mimetics. A structural simplification along with modifications of the central oxopiperazine scaffold and addressing the lipophilic interactions led to the development of peptidomimetics that inhibit PEX5-TbPEX14 PPI and display cellular activity against T. b. brucei. This approach provides an alternative approach towards the development of trypanocidal agents and may be generally useful for the design of helical mimetics as PPI inhibitors.