Search Results (676)

Birds are hosts to a diverse assemblage of vector-transmitted haemosporidian parasites. However, the true genetic diversity and many host–parasite interactions are still unknown, particularly in under-represented species groups such as wild doves and pigeons (Columbiformes). In this study, we examined the prevalence and lineage diversity of haemosporidian genera Plasmodium, Leucocytozoon, and Haemoproteus in three species of wild columbids, sampled in Germany. Examinations were performed by applying molecular methods (nested PCR and one-step multiplex PCR) and blood smear examination, and their respective advantages and disadvantages are discussed. In the case of the European Turtle Dove Streptopelia turtur, samples were collected along a west–east gradient throughout Germany, covering migratory birds from the Western and Central-Eastern flyway of this species. Although no infection was detected in the Stock Dove Columba oenas samples, 53% of Turtle Dove and 86% of Common Woodpigeon Columba palumbus harbored a parasite of at least one haemosporidian genus, revealing previously unknown lineage–host interactions. We were not able to demonstrate a correlation between infection status (presence or absence of infection based on PCR results) and parasitemia with condition based on the heterophil to lymphocyte ratio (H/L ratio). Neither lineage occurrence nor prevalence of infection followed any geographically specific patterns. Thus, haemosporidian lineages found in Turtle Doves could not be used as a marker of geographic origin that would allow the tracking of their nonbreeding distribution. Full article

Coinfection with parasites and viruses can exacerbate disease transmission, outcomes and therapy. This study searched the Web of Science, PubMed, Scopus and JSTOR databases for publications on the prevalence of parasitic coinfection in people living with viruses from 1 January 2005 to 30 April 2022, and 356 studies were included and systematically reviewed. A meta-analysis was performed to assess the global prevalence of and factors potentially associated with parasitic infection (helminths and protozoa) in virus-infected people, and the infection burden was estimated. A variety of parasites (29 families, 39 genera, and 63 species) and viruses (8 kinds) were identified. The prevalence of parasitic coinfection in (all) virus-infected people was estimated to be 21.34% (95% CI 17.58–25.10, 5593 of 29,190 participants) and 34.13% (95% CI 31.32–36.94, 21,243/76,072 participants) for helminths and protozoa, respectively. Specially, in human immunodeficiency virus (HIV)-infected people, the global prevalence was 19.96% (95% CI 16.18–23.74) for helminths and 34.18% (95% CI 31.33–37.03) for protozoa, respectively. The global prevalence of protozoa was 41.79% (95% CI 15.88–67.69) in hepatitis B virus (HBV)-infected people and 17.75% (95% CI 3.54–31.95) in DENV-infected people, respectively. The global burden of parasitic infections in HIV-infected people was 7,664,640 for helminths and 13,125,120 for protozoa, respectively, and that in HBV- and dengue virus (DENV)-infected people was 137,019,428 and 629,952, respectively. The prevalence of parasitic coinfection at the family, genus, and species levels in virus- or HIV-infected people were comprehensively estimated and further analyzed by subgroups. Among the most commonly identified parasites, the five helminth genera with the highest prevalence in HIV-infected people were Schistosoma (12.46%, 95% CI 5.82–19.10), Ascaris (7.82%, 95% CI 6.15–9.49), Strongyloides (5.43%, 95% CI 4.11–6.74), Trichuris (4·82%, 95% CI 2.48–7.17) and Ancylostoma (2.79%, 95% CI 1.32–4.27), whereas the top five protozoan genera were Toxoplasma (48.85%, 95% CI 42.01–55.69), Plasmodium (34.96%, 95% CI 28.11–41.82), Cryptosporidium (14.27%, 95% CI 11.49–17.06), Entamoeba (12.33%, 95% CI 10.09–14.57) and Blastocystis (10.61%, 95% CI 6.26–14.97). The prevalence of parasitic coinfection in virus-infected people was associated with income level. The findings provide valuable global epidemiological information for informing normative guidance, improving surveillance, and developing public healthcare strategies. Full article

Culicoides biting midges (Diptera: Ceratopogonidae) are important vectors of avian haemosporidian parasites. Understanding their host preferences is crucial for elucidating transmission routes of vector-borne pathogens. In Slovakia, such knowledge is limited, particularly in forested wetlands. This study aimed to identify Culicoides species, their host preferences, and haemosporidian parasites in a wetland ecosystem at the Bird Ringing Station in Drienovec. Midges were collected in 2022 using UV light traps at two sites. In total, 2344 Culicoides individuals of 19 species were collected. Host blood was identified and DNA subsequently extracted from 36 engorged females, revealing feeding on three mammal and five bird species. The most frequently identified host was roe deer (Capreolus capreolus), predominantly fed upon by Culicoides obsoletus (Meigen 1818). Notably, avian haemosporidian DNA was detected for the first time in Slovakia in three Culicoides females. In two Culicoides alazanicus Dzhafarov 1961 individuals, DNA of Haemoproteus asymmetricus (TUPHI01) and Plasmodium matutinum (LINN1) was confirmed, both associated with avian blood from Turdus sp. One Culicoides festivipennis Kieffer 1914 female carried Haemoproteus tartakovskyi (HAWF1) and fed on Coccothraustes coccothraustes. These findings highlight the potential role of local Culicoides species in transmitting avian pathogens and underscore the importance of monitoring their ecology. Full article

Background and Objectives: Malaria is a disease that can result in a variety of complications. Diagnosis is carried out by an optical microscope and depends on operator experience. The use of artificial intelligence to identify morphological patterns in erythrocytes would improve our diagnostic capability. The object of this study was therefore to establish computer viewing models able to classify blood cells infected with Plasmodium spp. to support malaria diagnosis by optical microscope. Materials and Methods: A total of 27,558 images of human blood sample extensions were obtained from a public data bank for analysis; half were of parasite-infected red cells (n = 13,779), and the other half were of uninfected erythrocytes (n = 13,779). Six models (five machine learning algorithms and one pre-trained for a convolutional neural network) were assessed, and the performance of each was measured using metrics like accuracy (A), precision (P), recall, F1 score, and area under the curve (AUC). Results: The model with the best performance was VGG-19, with an AUC of 98%, accuracy of 93%, precision of 92%, recall of 94%, and F1 score of 93%. Conclusions: Based on the results, we propose a convolutional neural network model (VGG-19) for malaria diagnosis that can be applied in low-complexity laboratories thanks to its ease of implementation and high predictive performance. Full article

Background/Objectives: Malaria, caused by infection with Plasmodium parasites, exacts a heavy toll worldwide. There are two licensed vaccines for malaria as well as two monoclonal antibodies that have shown promising efficacy in field trials. The vaccines and monoclonal antibodies target the major surface protein (circumsporozoite protein, CSP) of Plasmodium falciparum. Yet P. falciparum is only one of the four major species of Plasmodium that infect humans. Plasmodium vivax is the second leading cause of malaria, but the P. vivax vaccine and monoclonal development lags far behind that for P. falciparum owing to the lack of basic preclinical tools such as in vitro culture or mouse models that replicate the key biological features of P. vivax. Notably among these features is the ability to form dormant liver stages (hypnozoites) that reactivate and drive the majority of the P. vivax malaria burden. Plasmodium cynomolgi is a simian parasite which is genotypically very close and phenotypically similar to P. vivax; it can infect non-human primates commonly used in research and replicates many features of P. vivax, including relapsing hypnozoites. Methods: Recently, a strain of P. cynomolgi has been adapted to in vitro cultures allowing parasite transgenesis. Here, we created a transgenic P. cynomolgi parasite in which the endogenous P. cynomolgi CSP has been replaced with P. vivax CSP, with the goal of enabling the preclinical study of anti-P. vivax CSP interventions to protect against primary and relapse infections. Results: We show that the in vitro-generated transgenic Pcy[PvCSP] parasite expresses both serotypes of P. vivax CSP and retains full functionality in vivo, including the ability to transmit to laboratory-reared Anopheles mosquitoes and cause relapsing infections in rhesus macaques. To our knowledge, this is the first gene replacement in a relapsing Plasmodium species. Conclusions: This work can directly enable the in vivo development of anti-P. vivax CSP interventions and provide a blueprint for the study of relapsing malaria through reverse genetics. Full article

The serendipitous discovery of antiparasitic drugs, such as quinine and artemisinin, of plant origin reveals that searching new chemical pharmacophores from medicinal plants is valuable. The present study sought to explore the antiplasmodial, antileishmanial, and antitrypanosomal activities of Lippia adoensis extracts. Crude extracts of L. adoensis leaves and twigs, which were obtained by extraction using 70% ethanol in water, were assayed for antiplasmodial activity against P. falciparum 3D7 and Dd2 through the SYBR green I-based fluorescence assay; and for antileishmanial, antitrypanosomal, and cytotoxic effects on Leishmania donovani, Trypanosoma brucei brucei, and Vero cells, respectively, using resazurin colorimetric assays. In vitro phytochemical analysis of L. adoensis extracts was performed using standard methods. Moreover, liquid chromatography–mass spectrometry (LC-MS) feature-based detection and molecular networking flow on Global Natural Product Social (GNPS) were also used for the phytochemical screening of L. adoensis extracts. Crude extracts from L. adoensis inhibited the growth of P. falciparum (3D7 and Dd2) (IC₅₀s; (3D7): 10.00 and 97.46 μg/mL; (Dd2): 29.48 and 26.96 μg/mL), L. donovani (IC₅₀s: 22.87–10.52 μg/mL), and T. brucei brucei (IC₅₀s: 2.30–55.06 μg/mL). The extracts were found to be non-cytotoxic to Vero cells, thus yielding median cytotoxic concentrations (CC₅₀s) above 100 μg/mL. In vitro phytochemical analysis of the crude extracts revealed the presence of alkaloids, terpenoids, phenolic compounds, and carbohydrates. The LC-MS tandem molecular networking flow predicted that the extracts contained valsafungin A and bacillamidin in the first cluster, and fatty acids, ketone, and aldehyde derivatives in the second cluster. Overall, the present study demonstrated the antiparasitic effects of L. adoensis extracts, thus justifying the use of this plant in the traditional treatment of fever and malaria conditions. Nevertheless, detailed metabolomic studies and antiparasitic mechanisms of action of the extracts are expected to unveil the potential antiparasitic hit compounds. Full article

Plasmodium malariae is a neglected human malaria parasite despite its global distribution and propensity for persistent, sub-microscopic infections, which are associated with a mild but significant disease burden. Artemisinin-based therapies appear to be efficacious, but the susceptibility profiles of field isolates are largely unknown. We performed ex vivo assays with isolates collected from asymptomatic volunteers in Gabon. The mean concentrations required to inhibit 50% of growth (IC50) with chloroquine (n = 21), artesunate (n = 20), atovaquone (n = 21), and lumefantrine (n = 14) were 7.2 nM, 2.7 nM, 3.1 nM, and 7.4 nM, respectively. Our study provides novel data on the ex vivo susceptibility of P. malariae to several key antimalarials, including the first dataset for atovaquone. Full article

Background: Insecticide resistance challenges the vector control efforts towards malaria elimination and proving the development of complementary tools. Targeting the genes that are involved in mosquito fertility and susceptibility to Plasmodium with small molecule inhibitors has been a promising alternative to curb the vector population and drive the transmission down. However, such an approach would require a comprehensive knowledge of the genetic diversity of the targeted genes to ensure the broad efficacy of new tools across the natural vector populations. Methods: Four fertility and parasite susceptibility genes were identified from a systematic review of the literature. The Single Nucleotide Polymorphisms (SNPs) found within the regions spanned by these four genes, genotyped across 2784 wild-caught Anopheles gambiae s.l. from 19 sub-Saharan African (SSA) countries, were extracted from the whole genome SNP data of the Ag1000G project (Ag3.0). The population genetic analysis on gene-specific data included the determination of the population structure, estimation of the differentiation level between the populations, evaluation of the linkage between the non-synonymous SNPs (nsSNPs), and a few statistical tests. Results: As potential targets for small molecule inhibitors to reduce malaria transmission, our set of four genes associated with Anopheles fertility and their susceptibility to Plasmodium comprises the mating-induced stimulator of oogenesis protein (MISO, AGAP002620), Vitellogenin (Vg, AGAP004203), Lipophorin (Lp, AGAP001826), and Haem-peroxidase 15 (HPX15, AGAP013327). The analyses performed on these potential targets of small inhibitor molecules revealed that the genes are conserved within SSA populations of An. gambiae s.l. The overall low Fst values and low clustering of principal component analysis between species indicated low genetic differentiation at all the genes (MISO, Vg, Lp and HPX15). The low nucleotide diversity (>0.10), negative Tajima’s D values, and heterozygosity analysis provided ecological insights into the purifying selection that acts to remove deleterious mutations, maintaining genetic diversity at low levels within the populations. None of MISO nsSNPs were identified in linkage disequilibrium, whereas a few weakly linked nsSNPs with ambiguous haplotyping were detected at other genes. Conclusions: This integrated finding on the genetic features of major malaria vectors’ biological factors across natural populations offer new insights for developing sustainable malaria control tools. These loci were reasonably conserved, allowing for the design of effective targeting with small molecule inhibitors towards controlling vector populations and lowering global malaria transmission. Full article

The present study investigates the prevalence and diversity of Plasmodium and Trypanosoma infections in Allochrocebus solatus, a vulnerable primate species native to Gabon. Using molecular techniques like nested PCR and phylogenetic analysis, we found 34.0% infection rate for malaria parasites infection, 21.3% for Trypanosoma spp., and 12.8% co-infections. Additionally, Hepatocystis was exclusively detected among malaria parasites, while Trypanosoma brucei brucei, T. vivax, and T. congolense were identified. These results underscore the complex host–parasite interactions influenced by captivity and the ecological and immunological consequences of such infections, particularly the increased susceptibility associated with captivity-induced stress. This preliminary study highlights the need for ongoing surveillance to mitigate health risks in primates and prevent potential zoonotic spillovers, providing critical data for conservation efforts. Full article

Our understanding of the molecular mechanisms undergirding artemisinin (ART) resistance in Plasmodium falciparum is currently based on two organizing principles: reduced hemoglobin trafficking into the digestive food vacuole, resulting in lower levels of activated ART, and increased tolerance to ART-induced oxidative stress in the infected erythrocyte. We had previously proposed an extracellular vesicle (EV) export model of ART resistance in P. falciparum. This model predicts that EV abundance will be altered by ART exposure and that the peptide cargo of EVs from the ART-exposed condition will be enriched with aggregation-prone peptides. We tested the predictions of the EV export hypothesis in this study using in vitro culture assays of an ART-resistant transgenic line engineered on a 3D7 background (R561H) and a 3D7 knock-out line (PfVps60KO) with deficient EV production phenotype. EV enrichment was obtained from in vitro parasite culture supernatants via a series of ultracentrifugation and filtration steps, followed by size exclusion chromatography. A quality check on EVs was performed using dynamic light scattering. Liquid chromatography with tandem mass spectrometry was used to determine the proteome cargo from extracted EVs, and parasite peptides were queried for aggregation-prone tendency using open-access software. We report that dihydroartemisinin (DHA) exposure was positively correlated with EV abundance (coefficient estimate = 1038.58, confidence interval of 194.86–1882.30, and p-value = 0.018) and suggests that EV biogenesis is part of the parasite’s response to DHA/ART. Furthermore, our findings suggest the expression of a non-constitutive DHA-induced alternate EV biogenesis pathway as the PfVps60KO was observed to produce the highest number of EVs under DHA exposure. Finally, we show that EVs from both ART-susceptible and resistant parasites under DHA exposure carry a cargo of Chorein N-terminal domain-containing protein (PF3D7_1021700) with a high aggregation-prone index (prion-like domain [PrLD] score = 26.5) out of nine identified parasite peptides. The former of these findings is in concordance with the EV export hypothesis, which posits that the removal of DHA/ART-induced aggregated and/or misfolded peptides is critical to the parasite’s survival under DHA/ART exposure. This observation further implicates EVs in the development of the ART-resistant phenotype. However, the finding of one aggregation-prone peptide out of the nine parasite proteins in the EV cargo does not sufficiently support the EV export hypothesis. Future replicates of this study and further interrogations of the EV export hypothesis are needed. Full article

Malaria, the deadliest parasitic disease in the world, is sexually dimorphic, inflammatory, and oxidative. Males experience more severe symptoms and mortality than females do; therefore, the roles of 17β-estradiol and testosterone in this phenomenon have been studied. Both hormones affect oxidative stress, the primary mechanism of Plasmodium elimination. Estradiol has antioxidant activity, but the role of testosterone is controversial. Testosterone increases oxidative stress by reducing superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities, which increase lipoperoxidation in the testis. However, the antioxidant properties of testosterone in prostate and nervous tissue have also been reported. The discrepancies are probably because when testosterone levels increase, the aromatase enzyme transforms testosterone into estrogens that possess antioxidant activity, which masks the results. Therefore, it is unknown whether testosterone is involved in the sexual dimorphism that occurs in oxidative stress in malaria. In this work, we administered testosterone and simultaneously inhibited aromatase with letrozole to evaluate the role of testosterone in the sexually dimorphic pattern of oxidative stress that occurs in the blood, spleen, and brain of male and female CBA/Ca mice infected with Plasmodium berghei ANKA (P. berghei ANKA). Testosterone triggers parasitemia in males, who also display more oxidative stress than females in the absence of infection, leading to sexually dimorphic patterns. Interestingly, increasing testosterone levels in infected mice reduced oxidative stress in males and increased oxidative stress in females, reversing or eliminating the dimorphic patterns observed. Oxidative stress varies in each tissue; the brain was the most protected, while the blood was the greatest damaged. Our findings highlight the role of testosterone as a regulator of oxidative stress in a tissue and sex-specific manner; therefore, understanding the role of testosterone in malaria may contribute to the development of sex-specific personalized antimalarial therapies. Full article

Parasitic diseases pose a serious threat to the health of humans and the steady development of livestock husbandry. Although there are certain drug-based treatment methods, with the widespread application of drugs, various parasites are gradually developing drug resistance. Natural products are highly favored by researchers due to their characteristics such as low toxicity, multi-target effects, and low risk of drug resistance. The ocean, as the largest treasure trove of biological resources on Earth, has a special ecosystem (high pressure, high salt, and low oxygen). This enables marine organisms to develop a large number of unique structures during their survival competition. So far, a variety of compounds, such as terpenoids, have been isolated from the algae. As potential drugs, these compounds have certain curative effects on various diseases, including tumors, parasitic diseases, Alzheimer’s disease, and tuberculosis. This paper systematically reviews and analyzes the current advances in research on the antiparasite effects of seaweed extracts. The primary objective of this research is to formulate a conceptual foundation for marine pharmaceutical exploration, focusing on the creation of innovative marine-based medicinal compounds to overcome the emerging problem of parasite resistance to conventional treatments. Full article

Background: Malaria is a severe health problem in native communities of Condorcanqui in the Amazonas region of Peru. Recently, the number of malaria cases has increased considerably following a Plasmodium falciparum outbreak in 2019. However, there is no information on the anophelines acting as Plasmodium vectors in this area. This study aimed to identify Anopheles species circulating in previously unexplored native communities of Condorcanqui. Additionally, we sought to detect the presence of DNA from P. vivax and P. falciparum parasites in mosquitoes. Methods: During three exploratory visits between March and September 2022, 453 mosquitoes were collected using Shannon traps and CDC light traps. Only specimens morphologically identified as Anopheles sp. were subjected to molecular confirmation through PCR amplification and sequencing of the Cox1 barcode region. Plasmodium parasites were detected using nested PCR targeting of the 18S rRNA subunit, while human blood meal feeding was evaluated using a human β-globin marker. Results: A total of 66 specimens were molecularly confirmed as anopheline species: An. benarrochi B, An. triannulatus, An. Costai, and An. nimbus. Six specimens of An. benarrochi B were exclusively positive for Plasmodium parasites by PCR. Moreover, four specimens tested positive for Plasmodium and the presence of human blood, suggesting the anthropophilic behavior of An. benarrochi B and its possible role as a potential malaria vector in this area. Conclusions: In conclusion, while this study provides valuable insights into the potential role of Anopheles benarrochi as a malaria vector in Amazonas, further research is essential to fully understand its behavior and transmission dynamics in the region. Full article

Malaria primarily affects developing nations and is one of the most destructive and pervasive tropical parasite infections. Antimalarial drug resistance, characterized by a parasite’s ability to survive and reproduce despite recommended medication doses, poses a significant challenge. Along with resistance to antimalarial drugs, the rate of mutation a parasite undergoes, overall parasite load, drug potency, adherence to treatment, dosing accuracy, drug bioavailability, and the presence of poor-quality counterfeit drugs are some of the contributing factors that elicit opposition to treatment. The ubiquitin-proteasome system (UPS) has become a promising drug target for malaria because of its central importance in the parasite’s life cycle and its contribution to artemisinin resistance. Polymorphisms in the Kelch13 gene of Plasmodium falciparum are the best-known markers for artemisinin resistance and are associated with a highly active UPS. Certain proteasome inhibitors, which are the other key players of the UPS, have demonstrated activity against malarial parasites and the ability to work with artemisinin. This work describes how, through targeting the UPS, the greater effectiveness of antimalarial drugs—especially where there is strong resistance—can be achieved, which contributes to overcoming the drug resistance phenomenon in malaria. Full article

Malaria has been and remains a significant challenge in Africa and other endemic settings. Roughly, 95% of global morbidity and mortality due to malaria occurs within African populations and affects millions of individuals, especially those living in sub-Saharan countries, predominantly due to disease complications. Cultural factors such as unawareness of and disinterest in using recommended preventive tools and combating the primary host (i.e., the female Anopheles mosquito) play a significant role. This host transmits the malaria-causing Plasmodium parasite by biting an infected individual and spreading it to humans. The current overview focuses on the molecular markers associated with antimalarial drug resistance in Plasmodium falciparum (P. falciparum) in Rwanda, considered an exemplar of sub-Saharan countries where malaria is prevalent and effective policies on the development of malaria treatment, approved recently by WHO in 2025, have been adopted. The prevalence of mutations in key resistance genes, including pfcrt, pfmdr1, and pfdhfr/pfdhps, are linked to resistance against common antimalarial drugs such as chloroquine and sulfadoxine-pyrimethamine (SP). In addition, the Plasmodium falciparum kelch13 (pfk13) gene is linked to resistance against artemisinin, as its mutations can cause delayed parasite clearance and treatment failure. Despite changes in therapeutic use policies owing to high prevalence of variant alleles, which reduce the drug’s efficacy resistance to SP, the gene persists in Rwanda. Malaria parasites are becoming more resistant to chloroquine, leading to diminished effectiveness and slower recovery or treatment failure. Surveillance data reported from several studies provide crucial insights into the evolving trends of resistance markers and are vital for guiding treatment protocols and informing therapeutic use policy decisions. It is important that we continue to maintain and develop the effectiveness of malaria prevention strategies and treatments, due to the multiple types of resistance found in the population. Full article