Search Results (284)

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

Background: Neglected diseases caused by protozoan parasites remain a major public health burden, particularly in low- and middle-income countries. Among the chemical motifs explored in antiparasitic drug discovery, guanidine-containing compounds have attracted considerable attention due to their strong cationic character, high capacity for hydrogen bonding, and versatility in interacting with biological targets. Methodology: This review summarizes advances reported in the last decade regarding guanidine derivatives with activity against pathogens associated with Chagas disease, human African trypanosomiasis, Leishmaniasis, tuberculosis, toxoplasmosis, dengue and schistosomiasis. Results: Evidence gathered from synthetic, natural, and drug-repurposing studies indicates that the guanidine, guanidine-containing and guanidine-related compounds contribute to modulating biological activity by changing electrostatic interactions, hydrogen-bonding networks, and physicochemical properties, with enzymes, nucleic acids, and membrane-associated targets essential for parasite survival. Across the analyzed studies, several emerging structure–activity relationship trends were identified, including the contribution of polycationic or dicationic architectures, the influence of halogenated or lipophilic substituents, and the dependence of biological activity on the complete molecular framework, including heterocyclic systems, macrocycles, peptide conjugates, hybrid scaffolds, and repurposed drugs. In addition to direct antiparasitic effects, certain guanidine-containing and guanidine-related compounds demonstrate immunomodulatory or host-protective properties, expanding the therapeutic relevance of this class. Despite promising in vitro results, protonation trapping, efflux pump susceptibility, and pharmacokinetic limitations such as poor oral absorption, high polarity, plasma protein binding and limited membrane permeability remain significant challenges for clinical translation. Nonetheless, the integration of medicinal chemistry, computational modeling, and biological screening continues to accelerate the identification of optimized scaffolds. Conclusions: Overall, guanidine-based compounds constitute a promising scaffold for the development of new therapeutic strategies targeting neglected parasitic diseases, and further structural optimization may enable the emergence of candidates with improved efficacy, selectivity, and drug-like properties. Full article

Trypanosoma evansi (T. evansi) infection poses a significant health threat to equines. This study was aimed to assess the prevalence, risk factors, hematobiochemical alterations, and oxidative stress-mediated genotoxicity associated with equine trypanosomiasis in the Rahim Yar Khan District. This cross-sectional study was conducted on 384 equines from October 2024 to September 2025. Blood samples were collected for thin blood film microscopy and PCR assay using RoTat 1.2 primers. Hematological indices were analyzed with an automated hematology analyzer; serum biochemical parameters were quantified via standard assays. Oxidative stress markers, including malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH), were also measured. Genotoxicity was evaluated using the alkaline comet assay. Statistical analyses included the chi-square test, logistic regression, and independent t-tests. T. evansi was detected in 5.99% of samples by microscopy and 10.16% by PCR, with no significant association with species, age, or sex. Infected equines exhibited significant reductions in hemoglobin (5.4 ± 0.6 vs. 10.8 ± 0.5 g/dL; p < 0.0001), total serum protein (2.1 ± 0.3 vs. 5.8 ± 0.2 g/dL; p < 0.0001), albumin, and globulin, alongside elevated hepatic enzymes, blood urea nitrogen, and creatinine (all p < 0.01). Oxidative stress was confirmed by increased MDA (p < 0.0001) and decreased CAT activity (p < 0.001). Genotoxicity was significantly higher in infected animals (genetic damage index; 1.12 ± 0.08 vs. 0.40 ± 0.01; p < 0.01). This study provides the first integrated assessment of molecular epidemiology and oxidative stress-mediated genotoxicity in equines in this region, suggesting the pathogenic impact of the infection and targeted diagnostics for disease management strategies. 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

Suramin is a century-old polysulfonated naphthylurea that remains a first-line treatment for early-stage human African trypanosomiasis (HAT). Remarkably, despite its age, suramin continues to draw attention because of its unusually broad spectrum of biological activities. Historically known as an antagonist of purinergic (P2) receptors and an inhibitor of extracellular enzymes, suramin has more recently been shown to interact with a range of intracellular and mitochondrial proteins. These include succinate dehydrogenase, the ADP/ATP carrier (AAC), the aspartate/glutamate carriers AGC1 and AGC2, carnitine O-acetyltransferase (CRAT), and the ATP-Mg/Pi carrier (APC2). Across these targets, suramin displays sub-micromolar to low-micromolar potencies, largely driven by electrostatic complementarity between its highly anionic sulfonate groups and basic nucleotide- or anion-binding regions of proteins. This extensive polypharmacology helps explain the diverse biological effects reported for suramin and supports its use as a valuable pharmacological probe of mitochondrial transport and metabolism. At the same time, its largeness and high negative charge limit oral bioavailability and brain penetration, prompting efforts to develop simplified analogues. This review brings together chemical, biological, and structural perspectives on suramin, highlighting opportunities for drug repurposing, transporter-focused drug design, and a better understanding of mitochondrial toxicity. Full article

Some parasitic infections promote or inhibit vascular growth in their hosts to increase parasite survival through immune evasion and tissue dissemination. This review focuses on how the most prevalent protozoan and helminth parasites in humans, such as Plasmodium, Toxoplasma, Leishmania, Trypanosoma, Entamoeba, Schistosoma, and Taenia, manipulate angiogenic pathways for their own benefit. This knowledge reveals that angiogenesis is central to the pathophysiology and therapeutic targeting of parasitic diseases. Importantly, parasites and/or their excretory/secretory factors, which modulate vascular responses, are potential treatments for chronic degenerative diseases in which angiogenesis is crucial to disease progression, such as cancer. Full article

Trypanosoma vivax is a hemoprotozoan parasite of major veterinary importance affecting domestic ungulates in Africa and the Americas. While traditionally addressed within cattle-centered paradigms, accumulating evidence indicates that water buffaloes (Bubalus bubalis) are both clinically susceptible and epidemiologically significant hosts. This structured narrative review provides a host-centered synthesis of global evidence on T. vivax infection in buffaloes, integrating pathogenesis, transmission biology, epidemiology, diagnostics, chemotherapy, and integrated control. The analysis encompasses literature from 2000 to 2025 and incorporates seminal experimental studies published prior to 2000 that established buffalo susceptibility and reservoir competence. Evidence from cyclical (tsetse-mediated) and mechanical transmission systems is comparatively interpreted to clarify host–parasite dynamics. The Amazon biome is discussed as a model system for high-density buffalo production under mechanical vector pressure, offering case-based contextualization without geographic restriction. Particular attention is given to immunopathological mechanisms, chronic low-parasitemia carriage, diagnostic sensitivity in subclinical infections, emerging trypanocide resistance, and ecological constraints on vector control. Controversies and buffalo-specific knowledge gaps are highlighted throughout. By adopting a buffalo-centered analytical framework, this review supports translational diagnostics, targeted surveillance, and sustainable control strategies for trypanosomiasis in tropical livestock systems. Full article

Human African Trypanosomiasis (HAT) and Malaria are serious infectious diseases endemic in tropical regions, caused by protozoan parasites, and necessitating an urgent development of new antiprotozoal drugs. As part of our ongoing search for new antiprotozoal steroidal alkaloids from plants, we investigated the methanolic stem bark extract of Holarrhena pubescens (Apocynaceae). H. pubescens is a tropical tree that some Kenyan coastal communities have long used to treat various ailments, including fever and stomach pain. The crude extract, alkaloid fraction, and 16 subfractions acquired through centrifugal partition chromatography (CPC) displayed promising in vitro antiprotozoal activity against Trypanosoma brucei rhodesiense (Tbr) and Plasmodium falciparum (Pf). Partial least squares (PLS) regression modeling of UHPLC/+ESI QqTOF-MS data and the antiprotozoal activity data of the crude extract and its fractions was performed to predict compounds that may be responsible for the observed antiplasmodial activity. Chromatographic separation of the alkaloid fraction afforded one new steroidal alkaloid (5), along with 18 known compounds (1, 2, 4, 6–20), and one artifact (3) that was presumably formed during the acid–base extraction process. The structural characterization of the isolated compounds was accomplished using UHPLC/+ESI-QqTOF-MS/MS and NMR spectroscopy. The isolated compounds were tested for their in vitro antiprotozoal properties against the two aforementioned pathogens, as well as for their cytotoxicity against mammalian cells (L6 cell line). Compounds 2 and 16 (IC₅₀ = 0.2 μmol/L) demonstrated the highest antitrypanosomal activity, with compound 2 showing the highest selectivity (SI = 127). The new compound 5 exhibited the strongest antiplasmodial activity and selectivity against Pf (IC₅₀ = 0.7 μmol/L, SI = 43). Our findings provide further promising antiprotozoal leads for HAT and Malaria. Full article

Trypanosomiasis, caused by flagellated protozoa of the genus Trypanosoma, has recently emerged as a major threat to aquaculture in China, particularly in farmed large yellow croaker (Larimichthys crocea). Outbreaks lead to high mortality rates and severe economic losses. Conventional diagnostic tools, such as blood-smear microscopy and molecular assays including polymerase chain reaction or quantitative polymerase chain reaction (qPCR), are often limited by low sensitivity during early infection or by their dependence on sophisticated instruments and trained personnel, restricting their utility in field conditions. To address these challenges, a multienzyme isothermal rapid amplification (MIRA) assay coupled with a lateral-flow dipstick (LFD) was developed for the rapid detection of trypanosoma strains circulating in L. crocea targeting the 18S ribosomal ribonucleic acid gene. After optimizing primer-probe sets, the assay performance was evaluated using plasmid standards and a panel of common aquaculture pathogens. The MRA-LFD assay consistently detected plasmid DNA at concentrations as low as 0.01 fg/µL (≈2.1 copies/µL) and demonstrated no cross-reactivity with other pathogens. Using clinical DNA samples positive for Trypanosoma, the detection limit was 100 fg µL⁻¹. Validation with 150 tissue samples from fish with and without clinical symptoms demonstrated high diagnostic consistency (94%) with qPCR results, confirming the reliability of the assay. This MIRA-LFD platform provides a sensitive, specific and portable diagnostic tool for early detection of Trypanosoma infections in large yellow croaker, offering valuable support for surveillance and disease management in aquaculture. 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

Human African Trypanosomiasis (HAT; sleeping sickness) and Malaria are life-threatening protozoan infections in tropical regions, with limited treatment options. As part of our ongoing efforts to discover new aminosteroid alkaloids from the Buxaceae family with antiprotozoal activity, which might serve as leads to new drugs against these infections, we investigated the dichloromethane extract from the leaves of Buxus obtusifolia (Mildbr.) Hutch. collected in Kenya, a species native to Kenya and Tanzania. To the best of our knowledge, and based on the most recent comprehensive literature review, this study represents the first phytochemical investigation of this plant. The alkaloid-enriched fraction yielded a total of 24 aminosteroid alkaloids, including 18 hitherto undescribed compounds (2, 3, 5–9, 11, 12, 15–19, and 21–24), along with six known compounds, two of which (1 and 4) are described as constituents of a natural source for the first time. Obtusiaminocyclin (24) represents the first Buxus alkaloid with a novel carbocyclic steroid skeleton with a cyclopropane ring comprising C-9, C-19 and C-11 accompanied by an unprecedented amino bridge between C-3 and C-10. The structures of the isolated compounds were determined using UHPLC/+ESI-QqTOF-MS/MS and NMR spectroscopy. The total crude extract, the alkaloid-enriched fraction, CPC subfractions and all isolated compounds were tested for in vitro antiprotozoal activity against Trypanosoma brucei rhodesiense (Tbr, responsible for East African HAT) and Plasmodium falciparum (Pf, responsible for tropical Malaria) as well as cytotoxicity against mammalian cells (L6 cell line). Deoxycyclovirobuxeine-B (12) (IC₅₀ = 0.8 µmol/L, SI = 108) and 29-trimethoxybenzoyloxy-obtusibuxoline (5) (IC₅₀ = 0.5 µmol/L, SI = 11) showed the highest activities with good selectivity indices against Tbr and Pf, respectively. Consequently, our findings provide valuable aminosteroid candidates that can serve as promising leads in our ongoing search for new drugs against HAT and Malaria. Full article

Trypanosomiasis significantly impacts camel health and productivity, posing a major challenge to food security in regions with large camel populations. In this study, we investigated the microscopic and molecular prevalence, performed phylogenetic analysis, and explored risk factors associated with Trypanosoma evansi (T. evansi) infection in 400 randomly selected suspected camels (Camelus dromedarius) from 10 districts of Punjab, Pakistan. Blood samples were collected for microscopic examination of Giemsa/Field’s-stained smears, and three PCR primer sets (ITS1CF/BR, pMUTec, RoTat 1.2) were used to detect the presence of T. evansi. PCR-based prevalence was higher (14.8%; CI 11.4–18.6) as compared to the microscopic examination (8.3%; CI 5.7–11.4) of samples. The targeted primers amplified DNA fragments of 210, 205, and 478 base pairs, respectively. Phylogenetic analysis showed 100% homology between local isolates and those from India, Sudan, Malaysia, Egypt, and Kenya. Risk analysis identified female gender (OR 2.1) and being in Southern Punjab (OR: 1.9) as significant factors associated with disease. Significantly (p < 0.05) reduced total protein (5.51 ± 0.05), albumin (2.77 ± 0.04), and globulin (2.57 ± 0.06) levels were found in PCR-positive camels. This study provides new molecular and phylogenetic data on T. evansi in Pakistan. Full article

The conservation of agricultural animal resources holds significant importance for addressing future breeding demands and promoting sustainable utilization of regional livestock genetic resources. As one of China’s five major fine cattle breeds, Nanyang cattle exhibit notable characteristics, including strong adaptability and a docile temperament. Through whole-genome comparative analysis of the Nanyang cattle core conservation population and free-ranging populations in mountainous areas, this study systematically investigated the genetic diversity, population structure, and adaptive evolutionary mechanisms of this indigenous Chinese cattle breed. Population structure analysis revealed that both groups belong to a single genetic lineage of Nanyang cattle without significant genetic differentiation; however, the free-ranging population demonstrated a slower linkage disequilibrium decay rate. Combined F_ST and θπ ratio analyses identified 170 positively selected genes, with KEGG enrichment highlighting glutamatergic synapse and African trypanosomiasis immune pathways. PLCB4, as a shared gene across both pathways, may exert pleiotropic functions in environmental adaptation. The core conservation population likely exhibits reduced diversity in neuroplasticity-related genes under artificial selection, whereas the free-ranging population retained more genes associated with environmental adaptation and immune response. These findings provide genomic evidence for formulating differentiated conservation strategies for Nanyang cattle, necessitating balanced co-optimization of production trait breeding and natural adaptability preservation. Full article

Parasitic infections remain a major global health challenge, particularly in resource-limited settings where they are closely tied to poverty and inadequate sanitation. The increasing emergence of drug resistance and the limited accessibility of current therapies highlight the urgent need for novel, safe, and affordable alternatives. Mangifera indica L. (mango), a widely cultivated fruit tree deeply rooted in traditional medicine, has long been used to treat conditions symptomatic of parasitic diseases, including fever, diarrhea, and dysentery. Phytochemical investigations have revealed a rich spectrum of bioactive compounds, notably mangiferin, phenolic compounds and terpenoids, which exhibit antimicrobial, antioxidant, and immunomodulatory activities. This review critically synthesizes evidence on the antiparasitic potential of M. indica against protozoa, such as Plasmodium, Leishmania, Trypanosoma, Toxoplasma gondii, Entamoeba histolytica, and free-living amoebae, as well as helminths. Strongest evidence exists for malaria and helminth infections, where both crude extracts and isolated compounds demonstrated significant activity in vitro and in vivo. Encouraging but limited findings are available for leishmaniasis and trypanosomiasis, while data on toxoplasmosis and amoebiasis remain largely speculative. Variations in efficacy across studies are influenced by plant parts and extraction methods, with ethanolic extracts and mangiferin often showing superior results. Despite promising findings, mechanistic studies, standardized methodologies, toxicological evaluations, and clinical trials are scarce. Future research should focus on elucidating molecular mechanisms, exploring synergistic interactions with existing drugs, and leveraging advanced delivery systems to enhance bioavailability. Full article