Background: Sleeping Sickness, Human African Trypanosomiasis (HAT) is a vector- borne disease caused by Trypanosoma brucei (T.b). Sleeping sickness in Ethiopia was reported in 1967 for the first time. Recently in Southern parts of Ethiopia, in August 2022, five (5) cases of sleeping sickness (T. b. rhodesiense) were confirmed. Following this outbreak, the current investigation was aimed to identify the entomological and epidemiological drivers for the reemergence of HAT outbreak and recommend appropriate interventions. Methods: A cross sectional study design with descriptive data analysis was used. Tsetse fly collection and blood samples from cattle animals were taken. NGU and bio-conical traps were used to determine the distribution (density and abundance) of the vector. About 10μl of blood was collected from the marginal ear vein of 301 cattle animals using the heparinized microhematocrit capillary. The parasite detection was carried out through vector dissection under binocular stereo-microscope (magnification of 60X) and microscopic examination from serum of Animals using the Buffy coat method. Results: A total of 329 tsetse flies were captured and identified to Glosina (G.) pallidipes 259 (60.4%) and Glossina fuscipes 70 (16.3%). 188 (51.1%) of tsetse flies were collected from Dembagofa with 94 apparent density. Among all captured Tsetse flies, 39 (11.8%) of Tsetse were fed with high female apparent density in each ecological variation: wood land (51), Bush land (20) and grassland (11). Overall, the apparent density of tsetse fly was high in Wood land (93): G. pallidipes (76.5) and Bush land (36.5). Among all examined cattles for the presence of parasite, 9 cattles were detected positive with an overall prevalence of 3%. T. congolense 6 (2%) and T. vivax 1 (0.3%) with 2 (0.7%) suspected brucei. The parasite prevalence Trypanosoma was 4 (4.6%) in poor body condition (Bcs) cattle. The animals in the age range 5 - 9 years were infected high with 7 (5.3%) prevalence. Conclusion: The current study revealed that there are high-risk factors that predispose the community to Human African Trypanosomiasis (HAT) due to the presence of two different species of Tsetse flies and many animal reservoirs. The transmissions of Human African trypanosomiasis (HAT) are related to environmental, Vector, and human factors. Further geographically expanded investigation should be conducted throughout the country.

Animal trypanosomiasis (AT) is a complex of veterinary diseases known under various names such as nagana, surra, dourine and mal de caderas, depending on the country, the infecting trypanosome species and the host. AT is caused by parasites of the genus Trypanosoma, and the main species infecting domesticated animals are T. brucei brucei, T. b. rhodesiense, T. congolense, T. vivax, T. evansi and T. equiperdum. AT transmission, again depending on species, is through tsetse flies or common Stomoxys and tabanid flies or through copulation. Therefore, the geographical spread of all forms of AT together is not restricted to the habitat of a single vector like the tsetse fly and currently includes almost all of Africa, and most of South America and Asia. The disease is a threat to millions of companion and farm animals in these regions, creating a financial burden in the billions of dollars to developing economies as well as serious impacts on livestock rearing and food production. Despite the scale of these impacts, control of AT is neglected and under-resourced, with diagnosis and treatments being woefully inadequate and not improving for decades. As a result, neither the incidence of the disease, nor the effectiveness of treatment is documented in most endemic countries, although it is clear that there are serious issues of resistance to the few old drugs that are available. In this review we particularly look at the drugs, their application to the various forms of AT, and their mechanisms of action and resistance. We also discuss the spread of veterinary trypanocide resistance and its drivers, and highlight current and future strategies to combat it.

Human African Trypanosomiasis (HAT) commonly known as sleeping sickness, is a neglected tropical vector borne disease caused by trypanosome protozoa. It is transmitted by bites of infected tsetse fly. In this paper we first present the vector-host model which describes the general transmission dynamics of HAT. In the tsetse fly population, the HAT is modelled by three compartments while in the human population, the HAT is modelled by four compartments. The next generation matrix approach is used to derive the basic reproduction number, R₀, and also it is proved that if R₀ ≤ 1 the disease free equilibrium is globally asymptotically stable, which means the disease dies out. The disease persist in the population if the value of R₀ > 1. Furthermore, the optimal control model is determined by using the Pontryagin’s maximum principle with control measures such as education, treatment and insecticides used to optimize the objective function. The model simulations confirm that the use of the three control measures are very efficient and effective to eliminate HAT in Africa.

Pteridine reductase 1 is a trypanosomatid multifunctional enzyme that provides a mechanism for escape of Dihydrofolate reductase (DHFR) inhibition. This is because PTR1 can reduce pterins and folates. Trypanosomes require folates and pterins for survival and are unable to synthesize them de novo. Currently there are no anti-folate based Human African Trypanosomiasis (HAT) chemotherapeutics in use. Thus, successful dual inhibition of TbDHFR and TbPTR1 has implications in the exploitation of anti-folates. We carried out molecular docking of a ligand library of 5742 compounds against TbPTR1 and identified 18 compounds showing promising binding modes. The protein-ligand complexes were subjected to Molecular dynamics to characterize their molecular interactions and energetics followed by in vitro testing. In this study, we identified five potential TbPTR1 inhibitors that showed low micromolar Trypanosome growth inhibition in in vitro experiments with no significant human cell cytotoxicity. Compounds RUBi004, RUBi007, RUBi014, and RUBi018 displayed moderate to strong antagonism when used in combination with the known TbDHFR inhibitor, WR99210. This gave an indication that the compounds might inhibit both TbPTR1 and TbDHFR. RUBi016 showed an additive effect in the isobologram assay. Our results provide a basis for scaffold optimization for further studies in the development of HAT antifolates.

Unicellular eukaryotes of the Trypanosomatidae family include human and animal pathogens that belong to the Trypanosoma and Leishmania genera. Diagnosis of the diseases they caused requires the sampling of body fluids (blood, lymph, peritoneal fluid, cerebrospinal fluid, etc.) or organ biopsies (bone marrow, spleen, etc.), which are mostly obtained through invasive methods. Body fluids or appendages can be alternatives to these invasive biopsies but appropriateness remains poorly studied. To further address this question, we perform a systematic review on clues evidencing the presence of parasites, genetic material, antibodies, and antigens in body secretions, appendages, or the organs or proximal tissues that produce these materials. Paper selection was based on searches in PubMed, Web of Science, WorldWideScience, SciELO, Embase, Google. The information of each selected article (n=333) was classified into different sections and data were extracted from 77 papers. The presence of Trypanosomatidae parasites has been tracked in most of organs or proximal tissues that produce body secretions or appendages, in naturally or experimentally infected hosts. The meta-analysis highlights the paucity of studies on Human African Trypanosomiasis and a the absence on animal Trypanosomiasis. Among the collected data high heterogeneity in terms of the I² statistic (100%) is recorded. A high positivity is recorded for antibody and genetic material detection in urine of patients and dogs suffering leishmaniasis, and of antigen for leishmaniasis and Chagas disease. Data on conjunctival swab can be analyzed with molecular methods solely for dogs suffering canine visceral leishmaniasis. Saliva and hair/bristle showed a pretty good positivity that support their potential to be used for leishmaniasis diagnosis. In conclusion, our study pinpoints significant gaps that need to be filled in order to properly address the interest of body secretion and hair or bristle for the diagnosis of infections caused by Leishmania and by other Trypanosomatidae parasites.

Parasitic diseases continue represent a threat on a global scale, particularly among the poorest countries in the world. This is particularly because of the absence of vaccines, and in some cases, resistance against available drugs, currently being used for their treatment. In this review emphasis is laid on natural products and scaffolds from African medicinal plants (AMPs) for lead drug discovery and possible further development of drugs for the treatment of parasitic diseases. In the discussion, emphasis has been laid on alkaloids, terpenoids, quinones, flavonoids and narrower compound classes of compounds with micromolar range activities against Schistosoma, Trypanosoma and Leishmania species. Suggestions for future drug development from African medicinal plants have also been provided.

Folk medicine is widely used in Angola, even for human African trypanosomiasis (sleeping sickness) in spite of the fact that the reference treatment is available for free. Aiming to validate herbal remedies in use, we have selected nine medicinal plants and assessed their antitrypanosomal ac-tivity. 122 extracts were prepared using different plant parts and solvents. 15 extracts from seven different plants exhibited in vitro activity against Trypanosoma brucei rhodesiense bloodstream forms >70% at 20 µg/ml. The dichloromethane extract of Nymphaea lotus (leaves and leaflets) and the ethanolic extract of Brasenia schreberi (leaves) had IC50 values ≤10 µg/ml. These two aquatic plants are of particular interest. They are being co-applied in the form of a decoction of leaves because they are considered by local healers as male and female of the same species, the ethnotaxon “longa dia simbi”. Bioassay-guided fractionation led to the identification of eight active molecules: gallic acid (IC50 0.5 µg/ml), methyl gallate (IC50 1.1 µg/ml), 2,3,4,6-tetragalloyl-glucopyranoside, ethyl gallate (IC50 0.5µg/ml), 1,2,3,4,6-pentagalloyl-β-glucopyranoside (IC50 20µg/ml), gossypet-in-7-O-β-glucopyranoside (IC50 5.5µg/ml), and hypolaetin-7-O-glucoside (IC50 5.7µg/ml) in B. schreberi, and 5-[(8Z,11Z,14Z)-heptadeca-8,11,14-trienyl] resorcinol (IC50 5.3µg/ml) not described to date in N. lotus. Five of these active constituents were detected in the traditional preparation. This work provides the first evidence for the ethnomedicinal use of these plants in the management of sleeping sickness in Angola.