Search Results (200)

Human African trypanosomiasis (HAT) or sleeping sickness is a neglected tropical disease with a progressive central nervous system (CNS) involvement and marked sleep and circadian rhythm abnormalities. Even though this is a prominent feature of HAT, the connection between parasite neuroinvasion, neuroinflammation, circadian dysfunction, and neurological impairment is not fully understood. This narrative review aims to summarize the most up-to-date knowledge about sleep and circadian disturbance in HAT and proposes an integrated approach for the Trypanosome-Associated Sleep Disorder (TASD). The relevant literature was identified by searching major biomedical databases for HAT, sleep disorders, circadian rhythms, neuroinflammation, and CNS invasion. The review covers the steps by which the CNS becomes invaded, how the barriers are disrupted, how the CNS becomes activated by inflammatory responses, and how the hypothalamic and circadian regulatory networks are disrupted. The evidence suggests that excessive daytime sleepiness, fragmented nocturnal sleep, circadian misalignment, and neuropsychiatric manifestations are related to the activation of inflammatory cytokines, altered neurotransmitter signaling, activation of the kynurenine pathway, dysregulation of clock genes, and disruption of the suprachiasmatic nucleus. We also discuss TASD as a syndrome-like phenotype of CNS involvement and propose a three-stage model of sleep–wake dysfunction in HAT. The review unites these integral mechanisms in a single mechanistic framework to offer a unified understanding of the sleep pathology associated with HAT. There are still important gaps in our knowledge of biomarkers, disease staging, and irreversible neuronal damage, which indicate priorities for future research and better clinical management. Full article

The subgenus Megatrypanum Hoare, 1964, with the type species Trypanosoma theileri Laveran, 1902, comprises stercorarian trypanosomes of mammals. A substantial portion of this subgenus consists of T. theileri-like trypanosomes parasitizing cervids and bovids worldwide. Similar to most other members of the genus Trypanosoma that lack obvious economic importance, the biology of T. theileri-like trypanosomes remains poorly understood. In particular, fundamental aspects such as their host specificity, host–parasite interactions, and the morphology of developmental stages have been studied only to a limited extent. In this work, we provide a detailed description of the development and cellular organization of T. theileri-like trypanosomes in the horsefly Hybomitra montana using transmission electron microscopy (TEM). We show for the first time that T. theileri-like trypanosomes possess a well-developed cytostome–cytopharyngeal complex, morphologically similar to those in other stercorarian trypanosomes. This complex is present in the studied trypanosomes at the epimastigote stage and degrades during metacyclogenesis. In the host ileum, epimastigotes and trypomastigotes at different stages of metacyclogenesis are embedded in a fibrillar matrix that isolates them from the gut lumen. This promotes their accumulation in the vector, thereby increasing the efficiency of future infection of the vertebrate host, which occurs via contamination of the oral mucosa. Full article

Trypanosomiasis remains a major constraint to small ruminant production in sub-Saharan Africa, particularly among smallholder farmers. Although WAD goats are considered trypanotolerant because of their relatively low mortality during chronic infection, recent findings show that this survival is at the expense of reproductive efficiency. To back up this claim with scientific evidence, this review followed PRISMA guidelines and systematically searched PubMed, Scopus, and Web of Science for important studies published between January 1980 and February 2026. Search terms included African animal trypanosomiasis, Trypanosoma spp., WAD goats, reproductive dysfunction, trypanotolerance, oxidative stress, and hypothalamic–pituitary–gonadal axis. Of the 1245 retrieved articles, 14 met the inclusion criteria. Evidence from the included studies indicates that chronic trypanosome infection disrupts reproduction through interconnected mechanisms involving systemic inflammation, oxidative stress, endocrine imbalance, and impaired gonadal function. Available evidence suggests that T. brucei is frequently associated with ovarian dysfunction and embryonic loss, whereas T. congolense has been linked in some studies to uterine pathology and gestational reproductive disturbances. Female goats commonly exhibit irregular oestrous cycles, embryonic loss, and prolonged kidding intervals, while males develop impaired spermatogenesis, abnormal sperm morphology, and reduced testosterone levels. These reproductive impairments reduce kid output, milk yield, herd productivity, and household livelihood resilience. Integrated control strategies combining vector control, targeted chemotherapy, nutritional support, and selective breeding are essential for preserving both fertility and survival in trypanosome-endemic areas. Full article

Vector-borne protozoal infections—including babesiosis, theileriosis, hepatozoonosis, trypanosomosis, and leishmaniosis—impose a substantial burden on livestock and companion animal health worldwide and carry important zoonotic and public health implications. Accurate diagnosis is essential yet challenging, given the diversity of parasite genera, their markedly different tissue tropisms, and the uneven distribution of diagnostic resources across veterinary settings. This review provides an integrated overview of the principal diagnostic approaches available, structured around the biological logic that guides test selection in practice. Microscopic examination remains the first-line method; its strengths and limitations are discussed for intraerythrocytic parasites (Plasmodium spp., Babesia spp., Theileria spp., Cytauxzoon spp.—the latter two with additional extra-erythrocytic schizont stages in leukocytes and tissue macrophages, respectively), leukocyte-associated forms (Hepatozoon spp.), extracellular trypanosomes, and tissue-stage parasites, including emerging applications of artificial intelligence. Serological methods—enzyme-linked immunosorbent assay (ELISA), indirect fluorescence antibody test (IFAT), and point-of-care lateral flow assays—are evaluated for their role in exposure detection, population screening, and international trade certification, with attention to cross-reactivity and the active-versus-past-infection distinction. Molecular diagnostics, encompassing conventional PCR, qPCR, droplet digital PCR, isothermal amplification, and next-generation sequencing, are reviewed with respect to target selection, sensitivity, and point-of-care applicability. Finally, diagnostic challenges are contextualised within a One Health framework, highlighting the fragmentation of veterinary surveillance and the need for integrated, cross-sector approaches to detect emerging threats. Full article

Rhodesain is a cysteine protease that plays a key role in the life cycle of Trypanosoma brucei rhodesiense, an endemic parasite in sub-Saharan Africa and responsible for Human African Trypanosomiasis (HAT), a disease that can be fatal if not treated promptly. Due to the limitations associated with current HAT pharmacological therapy, the search for new targets for the development of antitrypanosomal agents is urgently needed; in this context, rhodesain represents a promising therapeutic target. In this study, new chalcones were synthesized and tested against rhodesain. Given their affinity for the trypanosomal cysteine protease (K_i values in the micromolar range), chalcone 1a was selected to evaluate its effect in combination with the nutraceutical curcumin. The Combination Index (CI) was calculated using Chou and Talalay’s method. The analysis of the CI calculated at different f_a values of enzyme inhibition for the combination curcumin + 1a showed promising results. For all f_a values, the CI is less than one, indicating a synergistic effect when chalcone 1a is combined with curcumin. In particular, at the most significant f_a value (0.90), corresponding to 90% of enzyme inhibition, the CI value is 0.1781, indicating a strong synergism between the synthetic drug and the nutraceutical. The combined use of curcumin and chalcone 1a led to an enhancement of rhodesain inhibitory activity, resulting in a strong synergistic effect and supporting further investigation of this combination. Full article

Equine trypanosomosis remains an important veterinary concern in regions where horses play a significant economic and cultural role. In Kazakhstan, comprehensive nationwide data on the seroepidemiological status of equine trypanosomes are limited. The aim of this study was to assess the serological distribution of equine trypanosomosis across all administrative regions of Kazakhstan using complement fixation testing (CFT). A total of 6065 equine serum samples were collected from seventeen regions between 2023 and 2025. Antibodies against members of the Trypanozoon subgenus were detected using a WOAH-recommended CFT protocol. Overall seropositivity was 4.73%, with substantial regional variation ranging from 0% to 16.52%. Statistically significant differences in seroprevalence were observed between regions (p < 0.001), and mixed-effects modelling indicated considerable regional clustering. PCR testing of seropositive samples did not confirm the presence of Trypanosoma equiperdum, while one sample tested positive for Trypanosoma evansi. These findings suggest that CFT seropositivity reflects exposure to equine trypanosomes rather than confirmed dourine infection. Given the inability of CFT to reliably distinguish between T. equiperdum and T. evansi, species-level attribution remains uncertain. This study provides the first nationwide overview of serological reactivity to equine trypanosomes in Kazakhstan. The results highlight regional heterogeneity in antibody detection and underscore the need for expanded molecular surveillance and improved species-specific diagnostic tools to clarify the epidemiological status of equine trypanosomosis in the country. Full article

During the first week of T. b. brucei infection, pro-inflammatory IFN-γ production drives acute anaemia by promoting red blood cell clearance by activated macrophages in concert with insufficient bone marrow compensation. The latter is followed by a partial recovery phase, which later progresses to chronic anaemia. To compensate for acute anaemia, stress-induced extramedullary erythropoiesis occurs in the spleen. However, the role of IL-10, a key anti-inflammatory cytokine in regulating stress-induced acute anaemia during African trypanosomosis (AT), remains unclear. Using both genetic and pharmacological approaches, we show that IL-10 is essential to limit acute anaemia by dampening inflammation and promoting splenic erythropoiesis, enabling recovery. More specifically, IL-10 blockade impairs erythropoiesis in both bone marrow and spleen, particularly at early erythroid differentiation stages, and associates with reduced central macrophage (CM) numbers in the bone marrow. In contrast, the co-inhibition of IL-10 and IFN-γ reduces inflammation and partially restores splenic CM numbers and erythropoiesis, highlighting IFN-γ’s suppressive role in erythropoiesis. Overall, these findings underscore IL-10’s key role in regulating stress-induced erythropoiesis during AT by modulating erythroid differentiation and CM abundance, thereby limiting immune-mediated acute anaemia. Consequently, timely adjustment of the IL-10/IFN-γ balance may enhance erythropoiesis and offer a potential therapeutic strategy to mitigate anaemia development. Full article

Background: In recent years, compounds known as Proteolysis Targeted Chimeras (PROTACs) have revitalized the field of bioactive molecule design. These compounds promote proteolysis of therapeutic targets by recruiting them to ubiquitin ligases. One of the most commonly used classes of compounds in the synthesis of PROTACs are immunomodulatory imides (IMiDs), such as thalidomide (TLD), which interact with the E3 ligase CRL4^CRBN via the CULT domain of the cereblon protein (CRBN). This domain has been identified in proteins across various phylogenetic groups, including trypanosomatids, leading to the hypothesis that IMiD-derived PROTACs should be active in these organisms. Methods: The trypanocidal activity of the PROTAC dBET1 and its separated components (JQ1 and TLD) were assayed using a T. cruzi strain expressing β-glalactosidase. Potential CRL4-E3L complexes from humans and trypanosomatids were assembled in silico with MultimerMapper. The IMiD-binding site of HsCRBN and its trypanosomatid homologs were analyzed using molecular dynamics and docking simulations. Results: We demonstrate that the compound dBET1 does not function as a PROTAC in Trypanosoma cruzi. In silico structural analysis of CRL4-E3L complex orthologs revealed that the trypanosomal CULT-containing protein is not part of such a complex. Molecular dynamics simulations showed that the pocket of this CULT domain is smaller than that of mammalian CRBN and cannot accommodate IMiDs within. Conclusions: We underscore the importance of functional and structural validation in drug discovery, particularly when extrapolating mechanisms between evolutionarily distant species. While PROTACs hold promise in human therapeutics, our work advocates for re-evaluating the rationale behind thalidomide-based PROTACs in trypanosomatid research. Full article

Tsetse flies are major vectors of trypanosomes in Sub-Saharan Africa, posing risks to livestock and human health. This study investigated the diversity, distribution, and infection rates of tsetse species, as well as the genetic diversity of drug resistance-associated trypanosome strains in Kenya. Flies were collected from Kwale, Taita-Taveta, Kajiado, Narok, and Turkana counties between November 2024 and February 2025. DNA analyses targeting rRNA and transporter genes (TbAT/P2, E6M6, DMT, TcoAde2) identified infections and resistance-associated mutations among 4693 sampled flies. Apparent density was highest in Kwale (101.52 flies/trap/day) and lowest in Turkana (1.18). Species distribution varied by county, with Kwale dominated by G. pallidipes, G. austeni, and G. brevipalpis; Taita-Taveta G. pallidipes, and G. brevipalpis; Kajiado G. pallidipes and G. longipennis; Narok G. pallidipes, G. brevipalpis, G. swynnertoni, and G. longipennis; and Turkana only G. pallidipes. Trypanosoma congolense was most prevalent, especially in Kwale, while T. brucei was common in Kajiado and Kwale. G. brevipalpis, G. austeni, and G. pallidipes showed higher infection risks. Drug resistance-associated T. congolense strains were found in Kwale and Taita-Taveta, with TcoAde2 and E6M6 gene diversity linked to Kenyan isolates. These findings highlight the need for targeted control of high-risk tsetse species and drug-resistant trypanosomes in Kenya. Full article

The mitochondrial DNA of trypanosomatid parasites consists of thousands of catenated minicircles and dozens of maxicircles that form a complex network structure, the kinetoplast (kDNA). Although kDNA replication and segregation during mitotic division are well studied, its inheritance during genetic exchange events remains unclear. In Trypanosoma brucei, hybrids inherit minicircles biparentally but retain maxicircles from a single parent. Although biparental inheritance of minicircles has been described in natural Trypanosoma cruzi hybrids, this process has not been explored in laboratory-generated hybrids of this parasite. In the present study, we analyzed kDNA inheritance in T. cruzi experimental hybrids using a comprehensive minicircle hypervariable region (mHVR) database and genome sequencing data. Our findings revealed biparental inheritance of minicircles, with hybrid lines retaining mHVRs from both parents for over 800 generations. In contrast, maxicircles were exclusively inherited from one parent. Unexpectedly, we observed an increase in kDNA content in hybrids, affecting both minicircles and maxicircles, and exhibiting instability over time. To explain these findings, we propose a Replicative Mixing (REMIX) model, where the hybrid inherits one kinetoplast from each parent and they are replicated allowing minicircle mixing. Instead maxicircle networks remain physically separated, leading to uniparental fixation after segregation in the first cell division of the hybrid. This model challenges previous assumptions regarding kDNA inheritance and provides a new framework for understanding kinetoplast dynamics in hybrid trypanosomes. Full article

African trypanosomiasis is a protozoan disease that affects both humans and animals. Human African Trypanosomiasis (HAT) is a Neglected Tropical Disease targeted for elimination in 2030. Although WHO has not reported HAT from Nigeria in the last decade, there are published studies reporting seroprevalence, parasite detection/isolation, and animal reservoirs potentially involved in HAT transmission in Nigeria. Interestingly, the burden of Animal African Trypanosomiasis (AAT) continues to increase. In this study, we synthesized published reports on the prevalence of HAT and AAT in Nigeria from 1993–2021, the trypanosome species involved, the spread of animal reservoirs, and the variability in diagnostic methodologies employed. A scoping review was performed following the methodological framework outlined in PRISMA-ScR checklist. Sixteen eligible studies published between 1993 and 2021 were reviewed: 13 for AAT and 3 for HAT. Varying prevalence rates were recorded depending on the diagnostic methods employed. The average prevalence reported from these studies was 3.3% (HAT), and 27.3% (AAT). Diagnostic methods employed include microscopy, PCR and Card Agglutination Test for Trypanosomiasis (CATT). Cattle, pigs, and dogs were identified as carriers of human-infective trypanosomes. This study highlights the scarcity of HAT epidemiological studies/data from Nigeria, the high prevalence, complex epidemiology, limited attention and surveillance of African Trypanosomiasis in Nigeria. Remarkably, WHO records do not reflect the published data showing evidence of HAT prevalence/cases in Nigeria. Unfortunately, diagnostics challenges and unrealistic disease reporting protocols seem to limit HAT reporting from Nigeria. Therefore, adequately coordinated epidemiological surveys and targeted intervention policies are imperative to ascertain the true epidemiological status of HAT in Nigeria and prevent disease re-emergence towards achieving WHO’s elimination targets. The presence of animal carriers of human-infective trypanosomes underscores the importance of a one-health approach to combat African trypanosomiasis effectively. Full article

Kinetoplastids are protozoa that possess a unique organelle called a kinetoplast. These include the parasites Trypanosoma cruzi, T. brucei and related African trypanosomes, and Leishmania spp. These parasites cause a variety of neglected tropical diseases in humans and livestock, with devastating consequences. In the absence of any vaccine, pharmaceutical interventions are the mainstay of control, but these have historically been underfunded, fragmented, and inadequately aligned with the complex zoonotic and ecological realities of the parasites’ transmission dynamics. In this review, the landscape of current and emerging drugs for treating leishmaniasis, Chagas disease, and African trypanosomiasis is critically evaluated across both veterinary and human contexts. It examines the challenges of legacy compounds, the pharmacological shortcomings in multi-host, multi-tropic and multi-stage disease systems, and the gaps in veterinary therapeutics, specifically for African animal trypanosomiasis and canine leishmaniasis but also the animal reservoir of T. cruzi. Emphasis is placed on pharmacokinetic divergence between species, the accompanying risks with the use of off-label human drugs in animals, and the ecological effects of environmental drug exposure. We propose a far-reaching One Health framework for pharmaceutical research and development, promoting dual-indication co-development, ecological pharmacology, regulatory harmonisation, and integrated delivery systems. In this context, we argue that the drug development pipeline must be rationalised as a transdisciplinary and ecologically embedded process, able to interrupt parasite transmission to human, animal, and vector interfaces. Our findings reveal that we can bridge age-old therapeutic gaps, advance towards sustainable control, and eventually eliminate the neglected diseases caused by kinetoplastid protozoan parasites by aligning pharmaceutical innovation with One Health principles. This article aims to promote future research and development of innovative drugs that are sustainable under the One Health framework. Full article

Information on Culicoides transmitted parasites, especially trypanosomatids, infecting animals and insects, is scarce. Our goal was to clarify the seasonal patterns of both Culicoides and trypanosomatids detected in these insects and the relationships between Culicoides abundance and meteorological parameters. UV light traps were used to collect biting midges in four study sites in 2022–2023; collected Culicoides females were dissected and analyzed using microscopy and PCR-based methods. Out of 1631 parous Culicoides females belonging to 14 different species, 6.5% were found to be infected with trypanosomatids (5.0% with at least three Trypanosoma species and 1.5% with monoxenous parasites). The highest Culicoides abundance was detected in June. The prevalence of trypanosomatids in biting midges increased during the summer (5.3% in June, 8.8% in July, and 11.2% in August). Temperature was recorded to be a presiding environmental gradient structuring Culicoides species composition, while wind speed and precipitation explained little of the variation. Our results indicate that both avian and mammalian trypanosomes can be found in these insects, although further research is needed to better understand the development of these parasites in biting midges and Culicoides vectorial capacity. Full article

The Apolipoprotein L1 (APOL1) innate immunity gene product represents the sole member of the APOL gene family in humans capable of secretion into circulation, thereby mediating the trypanolysis of T. brucei brucei. Gain-of-function variants of the APOL1 gene originated and spread among human population groups to extend APOL1’s protective capacity to include also serum-resistant subspecies, such as T. brucei gambiense (S342G known as APOL1-G1) and T. brucei rhodesiense (N388_Y389del known as APOL1-G2). The biochemical pathways underlying the lytic activity of these evolutionary favored mutations against bloodstream trypanosomes have been elucidated with remarkable precision. However, the intricate molecular mechanisms by which such variants confer an increased susceptibility to renal cellular injury and consequent kidney disease remain incompletely defined. In the absence of a consistent mechanistic explanation for differential kidney injury, we propose pursuing three interrelated avenues of investigation informed by prior epidemiological and mechanistic evidence linking them to APOL1’s cytotoxicity: (1) Molecular evolution of APOL1 haplotypes in human populations, (2) APOL1 splicing and consequent splice isoforms, (3) Interaction of APOL1 with other APOL gene family members, prioritizing APOL3. In the current study, we use reanalysis of population genetics datasets to resolve the haplotype contexts of all protein-altering APOL1 variants, uncovering previously unrecognized variant–haplotype couplings. We further characterize distinct cellular physiological properties among APOL1 splice isoforms, stressing the importance of isoform vB and what can be learned from isoform vC. Finally, a native interaction, and its interface, between APOL1 and APOL3 is reported, and shown to be differentially modulated by G1 and G2. We contend that continuing studies integrating these three interrelated domains will substantially advance mechanistic insights into APOL1 variant-driven renal injury, and leverage the findings to provide a more cohesive framework to guide future research. Full article

APOL1 is the most recent member of the APOL gene family and is expressed exclusively in humans and a few higher primates. More than twenty years ago, it was discovered that APOL1 protects humans from infections by trypanosome subspecies that cause African sleeping sickness. Interestingly, by a co-evolutionary process between parasite and host, two APOL1 variants emerged, which, in addition to their trypanotoxic effects, are simultaneously associated with a significantly increased risk for various different kidney diseases, which are now summarized as APOL1-mediated kidney diseases (AMKDs). The aim of this review is to highlight and formulate key aspects of APOL1’s cell biologic features, including questions and unaddressed aspects. This perspective may contribute to a deeper understanding of APOL1-associated cytotoxicity as well as AMKDs. Full article