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Zheng, Jingtong, He Pan, Yinuo Gu, Xu Zuo, Nan Ran, Yuze Yuan, Chao Zhang, and Fang Wang. "Prospects for Malaria Vaccines: Pre-Erythrocytic Stages, Blood Stages, and Transmission-Blocking Stages." BioMed Research International 2019 (October 3, 2019): 1–9. http://dx.doi.org/10.1155/2019/9751471.
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Malaria is a disease of public health importance in many parts of the world. Currently, there is no effective way to eradicate malaria, so developing safe, efficient, and cost-effective vaccines against this disease remains an important goal. Current research on malaria vaccines is focused on developing vaccines against pre-erythrocytic stage parasites and blood-stage parasites or on developing a transmission-blocking vaccine. Here, we briefly describe the progress made towards a vaccine against Plasmodium falciparum, the most pathogenic of the malaria parasite species to infect humans.
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Ozwara, Hastings, Jan A. M. Langermans, Clemens H. M. Kocken, Annemarie van der Wel, Peter H. van der Meide, Richard A. W. Vervenne, Jason M. Mwenda, and Alan W. Thomas. "Transfected Plasmodium knowlesi Produces Bioactive Host Gamma Interferon: a New Perspective for Modulating Immune Responses to Malaria Parasites." Infection and Immunity 71, no. 8 (August 2003): 4375–81. http://dx.doi.org/10.1128/iai.71.8.4375-4381.2003.
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ABSTRACT Transgenic pathogenic microorganisms expressing host cytokines such as gamma interferon (IFN-γ) have been shown to manipulate host-pathogen interaction, leading to immunomodulation and enhanced protection. Expression of host cytokines in malaria parasites offers the opportunity to investigate the potential of an immunomodulatory approach by generating immunopotentiated parasites. Using the primate malaria parasite Plasmodium knowlesi, we explored the conditions for expressing host cytokines in malaria parasites. P. knowlesi parasites transfected with DNA constructs for expressing rhesus monkey (Macaca mulatta) IFN-γ under the control of the heterologous P. berghei apical membrane antigen 1 promoter, produced bioactive IFN-γ in a developmentally regulated manner. IFN-γ expression had no marked effect on in vitro parasite development. Bioactivity of the parasite-produced IFN-γ was shown through inhibition of virus cytopathic effect and confirmed by using M. mulatta peripheral blood cells in vitro. These data indicate for the first time that it is feasible to generate malaria parasites expressing bioactive host immunomodulatory cytokines. Furthermore, cytokine-expressing malaria parasites offer the opportunity to analyze cytokine-mediated modulation of malaria during the blood and liver stages of the infection.
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Rendón-Franco, Emilio, Osvaldo López-Díaz, Fernando Martínez-Hernández, Guiehdani Villalobos, Claudia Irais Muñoz-García, Nidia Aréchiga-Ceballos, Jorge Alberto Alfonso-Toledo, María Martha García Flores, and Alvaro Aguilar Setién. "Litomosoides sp. (Filarioidea: Onchocercidae) Infection in Frugivorous Bats (Artibeus spp.): Pathological Features, Molecular Evidence, and Prevalence." Tropical Medicine and Infectious Disease 4, no. 2 (May 10, 2019): 77. http://dx.doi.org/10.3390/tropicalmed4020077.
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Bats can host pathogenic organisms such as viruses and fungi, but little is known about the pathogenicity of their parasites. Hemoparasites are frequently recorded in Neotropical bats, particularly Litomosoides (Filarioidea: Onchocercidae), but their pathogenic effect on bats is scarcely known. In this work, Litomosoides microfilariae were identified in four (8%) out of 51 sampled frugivorous bats belonging to three different species: Artibeus aztecus, Artibeus jamaicensis, and Artibeus lituratus, which are located in Yautepec, Morelos, Mexico. Two infected animals showed weakness, tachypnoea, and ecchymosis on their wings. In these animals, histopathology revealed microfilariae in the blood vessels of the lung, liver, and spleen. Both animals presented exudative pneumonia with congestion and concomitant edema, in addition to moderate arterial hypertrophy. Parasitemia was quantified in blood samples of the infected animals (>3000 parasites/mL). Phylogenetic analysis placed the obtained sequence inside the Litomosoides genus, reaching over 98% identity to the related species. Due to the relevance of bats in ecosystems, any new record of their parasite repertoire offers noteworthy insights into our understanding of the ecology and impact of new parasite species in bats.
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Adams, Dayvion R., Andrew J. Golnar, Sarah A. Hamer, Michel A. Slotman, and Gabriel L. Hamer. "Culex quinquefasciatus (Diptera: Culicidae) survivorship following the ingestion of bird blood infected with Haemoproteus sp. parasites." Parasitology Research 120, no. 7 (June 10, 2021): 2343–50. http://dx.doi.org/10.1007/s00436-021-07196-7.
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AbstractArthropod vectors are frequently exposed to a diverse assemblage of parasites, but the consequence of these infections on their biology and behavior are poorly understood. We experimentally evaluated whether the ingestion of a common protozoan parasite of avian hosts (Haemoproteus spp.; Haemosporida: Haemoproteidae) impacted the survivorship of Culex quinquefasciatus (Say) (Diptera: Culicidae). Blood was collected from wild northern cardinals (Cardinalis cardinalis) in College Station, Texas, and screened for the presence of Haemoproteus spp. parasites using microscopic and molecular methods. Experimental groups of Cx. quinquefasciatus mosquitoes were offered Haemoproteus-positive cardinal blood through an artificial feeding apparatus, while control groups received Haemoproteus-negative cardinal blood or domestic canary (Serinus canaria domestica) blood. Culex quinquefasciatus mosquitoes exposed to Haemoproteus infected cardinal blood survived significantly fewer days than mosquitoes that ingested Haemoproteus-negative cardinal blood. The survival of mosquitoes fed on positive cardinal blood had a median survival time of 18 days post-exposure and the survival of mosquitoes fed on negative cardinal blood exceeded 50% across the 30 day observation period. Additionally, mosquitoes that fed on canary controls survived significantly fewer days than cardinal negative controls, with canary control mosquitoes having a median survival time of 17 days. This study further supports prior observations that Haemoproteus parasites can be pathogenic to bird-biting mosquitoes, and suggests that Haemoproteus parasites may indirectly suppress the transmission of co-circulating vector-borne pathogens by modulating vector survivorship. Our results also suggest that even in the absence of parasite infection, bloodmeals from different bird species can influence mosquito survivorship.
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Gramaglia, Irene, Joyce Velez, Valery Combes, Georges E. R. Grau, Melanie Wree, and Henri C. van der Heyde. "Platelets activate a pathogenic response to blood-stage Plasmodium infection but not a protective immune response." Blood 129, no. 12 (March 23, 2017): 1669–79. http://dx.doi.org/10.1182/blood-2016-08-733519.
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Husnik, Filip. "Host–symbiont–pathogen interactions in blood-feeding parasites: nutrition, immune cross-talk and gene exchange." Parasitology 145, no. 10 (April 12, 2018): 1294–303. http://dx.doi.org/10.1017/s0031182018000574.
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AbstractAnimals are common hosts of mutualistic, commensal and pathogenic microorganisms. Blood-feeding parasites feed on a diet that is nutritionally unbalanced and thus often rely on symbionts to supplement essential nutrients. However, they are also of medical importance as they can be infected by pathogens such as bacteria, protists or viruses that take advantage of the blood-feeding nutritional strategy for own transmission. Since blood-feeding evolved multiple times independently in diverse animals, it showcases a gradient of host–microbe interactions. While some parasitic lineages are possibly asymbiotic and manage to supplement their diet from other food sources, other lineages are either loosely associated with extracellular gut symbionts or harbour intracellular obligate symbionts that are essential for the host development and reproduction. What is perhaps even more diverse are the pathogenic lineages that infect blood-feeding parasites. This microbial diversity not only puts the host into a complicated situation – distinguishing between microorganisms that can greatly decrease or increase its fitness – but also increases opportunity for horizontal gene transfer to occur in this environment. In this review, I first introduce this diversity of mutualistic and pathogenic microorganisms associated with blood-feeding animals and then focus on patterns in their interactions, particularly nutrition, immune cross-talk and gene exchange.
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Droleskey, R. E., T. M. Craig, A. J. Roussel, P. J. Holman, and L. H. Stanker. "The Use of Semi-Thick Sections to Evaluate the Association Between a Species of Theileria and the Erythrocyte Membrane." Microscopy and Microanalysis 3, S2 (August 1997): 111–12. http://dx.doi.org/10.1017/s1431927600007443.
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Relatively benign or mildly pathogenic strains of bovine Theileria, an intraerythrocytic protozoan parasite, have been reported in many parts of the world including T. mutans in Africa, T. buffeli in Australia, T. orientalis in Britain, and a Theileria sp. from the Southwestern United States (US). Although the Theileria found in the US has not been specifically speciated, it has been referred to as T. mutans-like and as T. orientalis (USA). Although cattle in the US infected with these Theileria spp. usually have a circulating parasitemia of less than 1% and are asymptomatic, recently an animal suffering from severe anemia was admitted to the Large Animal Clinic at Texas A&M University with a circulating parasitemia of over 50%.Parasites in Giemsa stained blood films were pleomorphic in shape, with some parasites apparently connected to the erythrocyte membrane (Fig. 1) by structures which appeared similar to the bar structure found within eland (Taurotragus oryx) erythrocytes parasitized by T. taurotragi. Examination by TEM revealed that in addition to the main body of the parasite, parasitized erythrocytes contained parasites which possessed cytoplasmic extensions and an interaction between the parasite and the erythrocyte membrane which involved invaginations of the erythrocyte membrane which appeared to be surrounded by parasite cytoplasm (Fig. 2).
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BUNBURY, N., E. BARTON, C. G. JONES, A. G. GREENWOOD, K. M. TYLER, and D. J. BELL. "Avian blood parasites in an endangered columbid: Leucocytozoon marchouxi in the Mauritian Pink Pigeon Columba mayeri." Parasitology 134, no. 6 (January 4, 2007): 797–804. http://dx.doi.org/10.1017/s0031182006002149.
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SUMMARYThere is increasing evidence that pathogens can play a significant role in species decline. This study of a complete free-living species reveals a cost of blood parasitism to an endangered host, the Pink Pigeon Columba mayeri, endemic to Mauritius. We investigated the prevalence and effect of infection of the blood parasite, Leucocytozoon marchouxi, in the free-living Pink Pigeon population. Overall, L. marchouxi infection prevalence detected was 18·3%. Juveniles were more likely to be infected than older birds and there was geographical variation in infection prevalence. Survival of birds infected with L. marchouxi was lower than that of uninfected birds to 90 days post-sampling. This study suggests that while common haematozoa are well tolerated in healthy adults, these parasites may have greater pathogenic potential in susceptible juveniles. The study is unusual given its completeness of species sampling (96%) within a short time-period, the accurate host age data, and its focus on blood parasites in a threatened bird species. Species for which long-term life-history data are available for every individual serve as valuable models for dissecting the contribution of particular pathogens to species decline.
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Homer, Mary J., Irma Aguilar-Delfin, Sam R. Telford, Peter J. Krause, and David H. Persing. "Babesiosis." Clinical Microbiology Reviews 13, no. 3 (July 1, 2000): 451–69. http://dx.doi.org/10.1128/cmr.13.3.451.
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SUMMARY Babesiosis is an emerging, tick-transmitted, zoonotic disease caused by hematotropic parasites of the genus Babesia. Babesial parasites (and those of the closely related genus Theileria) are some of the most ubiquitous and widespread blood parasites in the world, second only to the trypanosomes, and consequently have considerable worldwide economic, medical, and veterinary impact. The parasites are intraerythrocytic and are commonly called piroplasms due to the pear-shaped forms found within infected red blood cells. The piroplasms are transmitted by ixodid ticks and are capable of infecting a wide variety of vertebrate hosts which are competent in maintaining the transmission cycle. Studies involving animal hosts other than humans have contributed significantly to our understanding of the disease process, including possible pathogenic mechanisms of the parasite and immunological responses of the host. To date, there are several species of Babesia that can infect humans, Babesia microti being the most prevalent. Infections with Babesia species generally follow regional distributions; cases in the United States are caused primarily by B. microti, whereas cases in Europe are usually caused by Babesia divergens. The spectrum of disease manifestation is broad, ranging from a silent infection to a fulminant, malaria-like disease, resulting in severe hemolysis and occasionally in death. Recent advances have resulted in the development of several diagnostic tests which have increased the level of sensitivity in detection, thereby facilitating diagnosis, expediting appropriate patient management, and resulting in a more accurate epidemiological description.
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Mayor, Alfredo, Nivedita Bir, Ritica Sawhney, Shailja Singh, Priyabrata Pattnaik, Saurabh Kumar Singh, Amit Sharma, and Chetan E. Chitnis. "Receptor-binding residues lie in central regions of Duffy-binding–like domains involved in red cell invasion and cytoadherence by malaria parasites." Blood 105, no. 6 (March 15, 2005): 2557–63. http://dx.doi.org/10.1182/blood-2004-05-1722.
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AbstractErythrocyte invasion by malaria parasites and cytoadherence of Plasmodium falciparum-infected erythrocytes to host capillaries are 2 key pathogenic mechanisms in malaria. The receptor-binding domains of erythrocyte-binding proteins (EBPs) such as Plasmodium falciparum EBA-175, which mediate invasion, and P falciparum erythrocyte membrane protein 1 (PfEMP-1) family members, which are encoded by var genes and mediate cytoadherence, have been mapped to conserved cysteine-rich domains referred to as Duffy-binding–like (DBL) domains. Here, we have mapped regions within DBL domains from EBPs and PfEMP-1 that contain receptor-binding residues. Using biochemical and molecular methods we demonstrate that the receptor-binding residues of parasite ligands that bind sialic acid on glycophorin A for invasion as well as complement receptor-1 and chondroitin sulfate A for cytoadherence map to central regions of DBL domains. In contrast, binding to intercellular adhesion molecule 1 (ICAM-1) requires both the central and terminal regions of DBLβC2 domains. Determination of functional regions within DBL domains is the first step toward understanding the structure-function bases for their interaction with diverse host receptors.
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Ferreira, Luciana de Lima, Fernanda Fortes de Araújo, Patricia Massara Martinelli, Andrea Teixeira-Carvalho, Juliana Alves-Silva, and Alessandra Aparecida Guarneri. "New features on the survival of human-infective Trypanosoma rangeli in a murine model: Parasite accumulation is observed in lymphoid organs." PLOS Neglected Tropical Diseases 14, no. 12 (December 28, 2020): e0009015. http://dx.doi.org/10.1371/journal.pntd.0009015.
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Trypanosoma rangeli is a non-pathogenic protozoan parasite that infects mammals, including humans, in Chagas disease-endemic areas of South and Central America. The parasite is transmitted to a mammalian host when an infected triatomine injects metacyclic trypomastigotes into the host′s skin during a bloodmeal. Infected mammals behave as parasite reservoirs for several months and despite intensive research, some major aspects of T. rangeli-vertebrate interactions are still poorly understood. In particular, many questions still remain unanswered, e.g. parasite survival and development inside vertebrates, as no parasite multiplication sites have yet been identified. The present study used an insect bite transmission strategy to investigate whether the vector inoculation spot in the skin behave as a parasite-replication site. Histological data from the skin identified extracellular parasites in the dermis and hypodermis of infected mice in the first 24 hours post-infection, as well as the presence of inflammatory infiltrates in a period of up to 7 days. However, qPCR analyses demonstrated that T. rangeli is eliminated from the skin after 7 days of infection despite being still consistently found on circulating blood and secondary lymphoid tissues for up to 30 days post-infection. Interestingly, significant numbers of parasites were found in the spleen and mesenteric lymph nodes of infected mice during different periods of infection and steady basal numbers of flagellates are maintained in the host′s bloodstream, which might behave as a transmission source to insect vectors. The presence of parasites in the spleen was confirmed by fluorescent photomicrography of free and cell-associated T. rangeli forms. Altogether our results suggest that this organ could possibly behave as a T. rangeli maintenance hotspot in vertebrates.
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Sándor, Attila D., Áron Péter, Alexandra Corduneanu, Levente Barti, István Csősz, Zsuzsa Kalmár, Sándor Hornok, Jenő Kontschán, and Andrei D. Mihalca. "Wide Distribution and Diversity of Malaria-Related Haemosporidian Parasites (Polychromophilus spp.) in Bats and Their Ectoparasites in Eastern Europe." Microorganisms 9, no. 2 (January 22, 2021): 230. http://dx.doi.org/10.3390/microorganisms9020230.
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Malaria is responsible for major diseases of humans, while associated haemosporidians are important factors in regulating wildlife populations. Polychromophilus, a haemosporidian parasite of bats, is phylogenetically close to human-pathogenic Plasmodium species, and their study may provide further clues for understanding the evolutionary relationships between vertebrates and malarial parasites. Our aim was to investigate the distribution of Polychromophilus spp. in Eastern Europe and test the importance of host ecology and roost site on haemosporidian parasite infection of bats. We sampled bats and their ectoparasites at eight locations in Romania and Bulgaria. DNA was extracted from blood samples and ectoparasites and tested individually for the presence of DNA of Polychromophilus spp. using a nested PCR targeting a 705 bp fragment of cytB. Two species of Polychromophilus were identified: Po. melanipherus in Miniopterus schreibersii and associated ectoparasites and Po. murinus in rhinolophid and vespertilionid bats (6 species) and their ticks and nycteribiid flies. Only cave-dwelling bat species (and their ectoparasites) showed infections, and we found a strong correlation between infections with Polychromophilus parasites and Nycteribiidae prevalence. We report the high genetic diversity of Polychromophilus spp. in Eastern Europe, suggesting that the simultaneous presence of varied host and vector assemblages enhances bat haemosporidian parasite diversity.
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Merino, Santiago, Juan Moreno, Juan José Sanz, and Elena Arriero. "Are avian blood parasites pathogenic in the wild? A medication experiment in blue tits ( Parus caeruleus )." Proceedings of the Royal Society of London. Series B: Biological Sciences 267, no. 1461 (December 22, 2000): 2507–10. http://dx.doi.org/10.1098/rspb.2000.1312.
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Voronin, Denis V., Anastasiia A. Kozlova, Roman A. Verkhovskii, Alexey V. Ermakov, Mikhail A. Makarkin, Olga A. Inozemtseva, and Daniil N. Bratashov. "Detection of Rare Objects by Flow Cytometry: Imaging, Cell Sorting, and Deep Learning Approaches." International Journal of Molecular Sciences 21, no. 7 (March 27, 2020): 2323. http://dx.doi.org/10.3390/ijms21072323.
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Flow cytometry nowadays is among the main working instruments in modern biology paving the way for clinics to provide early, quick, and reliable diagnostics of many blood-related diseases. The major problem for clinical applications is the detection of rare pathogenic objects in patient blood. These objects can be circulating tumor cells, very rare during the early stages of cancer development, various microorganisms and parasites in the blood during acute blood infections. All of these rare diagnostic objects can be detected and identified very rapidly to save a patient’s life. This review outlines the main techniques of visualization of rare objects in the blood flow, methods for extraction of such objects from the blood flow for further investigations and new approaches to identify the objects automatically with the modern deep learning methods.
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Schüler, Herwig, Ann-Kristin Mueller, and Kai Matuschewski. "A Plasmodium Actin-depolymerizing Factor That Binds Exclusively to Actin Monomers." Molecular Biology of the Cell 16, no. 9 (September 2005): 4013–23. http://dx.doi.org/10.1091/mbc.e05-02-0086.
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ADF/cofilins (AC) are essential F- and G-actin binding proteins that modulate microfilament turnover. The genome of Plasmodium falciparum, the parasite causing malaria, contains two members of the AC family. Interestingly, P. falciparum ADF1 lacks the F-actin binding residues of the AC consensus. Reverse genetics in the rodent malaria model system suggest that ADF1 performs vital functions during the pathogenic red blood cell stages, whereas ADF2 is not present in these stages. We show that recombinant PfADF1 interacts with monomeric actin but does not bind to actin polymers. Although other AC proteins inhibit nucleotide exchange on monomeric actin, the Plasmodium ortholog stimulates nucleotide exchange. Thus, PfADF1 differs in its biochemical properties from previously known AC proteins and seems to promote turnover exclusively by interaction with actin monomers. These findings provide important insights into the low cytosolic abundance and unique turnover characteristics of actin polymers in parasites of the phylum Apicomplexa.
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Untucht, Christopher, Janine Rasch, Elena Fuchs, Manfred Rohde, Simone Bergmann, and Michael Steinert. "An optimized in vitro blood–brain barrier model reveals bidirectional transmigration of African trypanosome strains." Microbiology 157, no. 10 (October 1, 2011): 2933–41. http://dx.doi.org/10.1099/mic.0.049106-0.
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The transmigration of African trypanosomes across the human blood–brain barrier (BBB) is the critical step during the course of human African trypanosomiasis. The parasites Trypanosoma brucei gambiense and T. b. rhodesiense are transmitted to humans during the bite of tsetse flies. Trypanosomes multiply within the bloodstream and finally invade the central nervous system (CNS), which leads to the death of untreated patients. This project focused on the mechanisms of trypanosomal traversal across the BBB. In order to establish a suitable in vitro BBB model for parasite transmigration, different human cell lines were used, including ECV304, HBMEC and HUVEC, as well as C6 rat astrocytes. Validation of the BBB models with Escherichia coli HB101 and E. coli K1 revealed that a combination of ECV304 cells seeded on Matrigel as a semi-synthetic basement membrane and C6 astrocytes resulted in an optimal BBB model system. The BBB model showed selective permeability for the pathogenic E. coli K1 strain, and African trypanosomes were able to traverse the optimized ECV304–C6 BBB efficiently. Furthermore, coincubation indicated that paracellular macrophage transmigration does not facilitate trypanosomal BBB traversal. An inverse assembly of the BBB model demonstrated that trypanosomes were also able to transmigrate the optimized ECV304–C6 BBB backwards, indicating the relevance of the CNS as a possible reservoir of a relapsing parasitaemia.
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Aguiar, Lívia Mendonça de, and Oswaldo Marçal Júnior. "Haemoparasites in captive birds at Uberlândia zoo, state of Minas Gerais, Brazil." Bioscience Journal 37 (January 28, 2021): e37011. http://dx.doi.org/10.14393/bj-v37n0a2021-47818.
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Haemoparasites are one of the most important groups of bird parasites, with emphasis on the genera Haemoproteus, Plasmodium, Leucocytozoon and Trypanosoma. Zoos sustain different wild animals and are valuable tools for the education and conservation of species. The conditions of captive animals differ from wild animals, as zoos have sufficient availability of food throughout the year, protection against predators and veterinary care for animals. This study aimed to determine the prevalence of haemoparasites in captive birds of the Sabiá Municipal Park Zoo, municipality of Uberlândia, state of Minas Gerais, Brazil. Blood samples were collected from the alveolar vein puncture to make blood swabs. This material was fixed with methanol, stained by the GIEMSA technique and examined under optical microscope. A total of 46 birds (19 species) were analyzed and only three individuals (6.52%) were positive for Plasmodium sp. The hosts were Pavo cristatus and Tyto furcata. This low positivity was expected, since haemoparasites do not generally present high infection rates among birds. Even if a parasite is not pathogenic for a given species, these individuals are important reservoirs for the infection of more vulnerable species. Differences in the prevalence and intensity of infection of these hosts depend on the virulence of the parasite, ability of the host to respond to such infections and vector availability. This low prevalence rate suggests a good health status of the captive birds in the study area.
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Mosli, Mahmoud, Jamie Gregor, Nilesh Chande, and Robert Lannigan. "Nonutility of routine testing of stool for ova and parasites in a tertiary care Canadian centre." Canadian Journal of Microbiology 58, no. 5 (May 2012): 653–59. http://dx.doi.org/10.1139/w2012-039.
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Background In many clinical situations, stool examinations for ova and parasites (O&P) are routine in the work-up of patients with acute or chronic diarrhea. Frequently, these tests are found to be negative for pathogens. The purpose of this study was to examine the diagnostic yield of routine stool testing for O&P in a Canadian tertiary care centre and to estimate the potential clinical benefit of a positive result. Patients and Methods All stool samples sent to the central microbiology laboratory at London Health Sciences Centre were reviewed over a 5-year period ending January 2010. Initial screening was done by direct antigen testing using an enzyme immunoassay (EIA) technique followed by direct microscopy for negative results where there was a high index of suspicion and for positive results to rule out any concurrent parasites not included in the EIA kit. Pathogens identified were categorized and their potential susceptibility to metronidazole was estimated. No clinical data were available, as this was purely a utilization study. Results A total of 5812 stool tests were ordered. Of these, 5681 (97.7%) were completed. The most common reasons for an incomplete test were sample leakage (n = 38) and use of the incorrect collection kit (n = 32). Direct microscopy identified white blood cells in 17% of patients with positive testing. The most common pathogen was Giardia lamblia , which was detected in 45/83 (54%) of positive specimens. Entamoeba histolytica / Entamoeba dispar was identified in 16/83 (19%) and Cryptosporidium spp. in 10/83 (12%) of positive specimens. Microorganisms not thought to be pathogenic were identified in 7/83 (8%). Direct laboratory costs independent of labor were estimated at $1836 per clinically significant organism identified. Of the 77 specimens positive for pathogenic organisms, 62 (81%) were likely to be sensitive to treatment with metronidazole. Conclusion In a tertiary care centre, the diagnostic yield of routine testing of stool for O&P during the evaluation of patients with acute or chronic diarrhea is low. Most clinically significant positive results should be responsive to metronidazole, but empirical treatment is not encouraged. Strategies to identify patients with a higher likelihood of harboring pathogenic parasites and consideration of empiric metronidazole therapy for patients at highest risk merit further research.
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Akhoundi, Mohammad, Denis Sereno, Anthony Marteau, Christiane Bruel, and Arezki Izri. "Who Bites Me? A Tentative Discriminative Key to Diagnose Hematophagous Ectoparasites Biting Using Clinical Manifestations." Diagnostics 10, no. 5 (May 15, 2020): 308. http://dx.doi.org/10.3390/diagnostics10050308.
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Arthropod blood feeders are vectors of several human pathogenic agents, including viruses (e.g., yellow fever, chikungunya, dengue fever), parasites (e.g., malaria, leishmaniasis, lymphatic filariasis), or bacteria (e.g., plague). Besides their role as a vector of pathogens, their biting activities cause a nuisance to humans. Herein, we document clinical symptoms associated with the biting of ten clusters of hematophagous arthropods, including mosquitoes, biting midges and sandflies, lice, ticks, tsetse flies, blackflies, horse flies, fleas, triatomine and bed bugs. Within the framework of clinical history and entomo-epidemiological information, we propose a tentative discriminative key that can be helpful for practicing physicians in identifying hematophagous arthropods biting humans and delivering treatment for the associated clinical disorders.
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ZUO, X., and P. T. K. WOO. "Natural anti-proteases in rainbow trout, Oncorhynchus mykiss and brook charr, Salvelinus fontinalis and the in vitro neutralization of fish α2-macroglobulin by the metalloprotease from the pathogenic haemoflagellate, Cryptobia salmositica." Parasitology 114, no. 4 (April 1997): 375–82. http://dx.doi.org/10.1017/s0031182096008578.
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Natural anti-proteases (α1-protease inhibitor (α1-PI; α1-antitrypsin) and α2-macroglobulin (α2-M)) were found in the blood of rainbow trout, Oncorhynchus mykiss and brook charr, Salvelinus fontinalis. The α2-M inhibited Cryptobia salmositica proteases and was significantly higher in brook charr than in rainbow trout. Under in vitro conditions it took longer for the same number of parasites to neutralize the α2-M in charr than in trout blood. The haemolysis which occurred when C. salmositica was incubated in the blood of rainbow trout was due to neutralization of α2-M. This in vitro study also showed that it was the metalloprotease of C. salmositica that lysed red blood cells and the plasma of the two species of fishes initially prevented haemolysis by inhibiting the proteolytic activity. We suggest that the natural plasma α2-M plays an important role in defence against cryptobiosis in fishes.
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Kaminsky, Ronald, and Reto Brun. "In Vitro and In Vivo Activities of Trybizine Hydrochloride against Various Pathogenic Trypanosome Species." Antimicrobial Agents and Chemotherapy 42, no. 11 (November 1, 1998): 2858–62. http://dx.doi.org/10.1128/aac.42.11.2858.
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ABSTRACT Trybizine hydrochloride [O,O′-bis(4,6-diamino-1,2-dihydro-2,2-tetramethylene-s-triazine-1-yl)-1,6-hexanediol dihydrochloride] was active in vitro against the sleeping sickness-causing agents Trypanosoma brucei subsp.rhodesiense and T. brucei subsp.gambiense; against a multidrug-resistant organism, T. brucei subsp. brucei; and against animal-pathogenic organisms Trypanosoma evansi, Trypanosoma equiperdum, and Trypanosoma congolense; but not against the intracellular parasites Trypanosoma cruzi andLeishmania donovani. Cytotoxic effects against mammalian cells were observed at approximately 106-fold higher concentrations than those necessary to inhibit T. bruceisubsp. rhodesiense. Trybizine hydrochloride was able to eliminate T. brucei subsp. rhodesiense andT. brucei subsp. gambiense in an acute rodent model with four intraperitoneal doses of 0.25 mg kg of body weight−1 or four doses of 1 mg kg−1, respectively, or with four oral doses of 20 mg kg−1. The compound expressed activity against suramin-resistant T. evansi strains in mice. However, these concentrations were not sufficient to cure mice infected with multidrug-resistant T. brucei subsp. brucei. A late-stage rodent model with central nervous system involvement could not be cured, indicating that trybizine may not pass the blood-brain barrier in sufficient quantities.
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Gabrie, José Antonio, María Mercedes Rueda, Carol Anahelka Rodríguez, Maritza Canales, and Ana Lourdes Sanchez. "Immune Profile of Honduran Schoolchildren with Intestinal Parasites: The Skewed Response against Geohelminths." Journal of Parasitology Research 2016 (2016): 1–13. http://dx.doi.org/10.1155/2016/1769585.
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Soil-transmitted helminth infections typically induce a type-2 immune response (Th2), but no immunoepidemiological studies have been undertaken in Honduras, an endemic country where the main control strategy is children’s annual deworming. We aimed to characterize the immune profile of Honduran schoolchildren harbouring these parasitoses. Demographic and epidemiological data were obtained through a survey; nutritional status was assessed through anthropometry; intestinal parasites were diagnosed by formol-ether and Kato-Katz; and blood samples were collected to determine immunological markers including Th1/Th2 cytokines, IgE, and eosinophil levels. A total of 225 children participated in the study, all of whom had received deworming during the national campaign five months prior to the study. Trichuriasis and ascariasis prevalence were 22.2% and 20.4%, respectively. Stunting was associated with both age and trichuriasis, whereas ascariasis was associated with sex and household conditions. Helminth infections were strongly associated with eosinophilia and hyper-IgE as well as with a Th2-polarized response (increased levels of IL-13, IL-10, and IL4/IFN-γ ratios and decreased levels of IFN-γ). Pathogenic protozoa infections were associated with a Th1 response characterized by elevated levels of IFN-γ and decreased IL10/IFN-γ ratios. Even at low prevalence levels, STH infections affect children’s nutrition and play a polarizing role in their immune system.
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Zhang, Yan Kai, and Jing Ze Liu. "Maternally inherited symbiotic bacteria in ticks: incidence and biological importance." Systematic and Applied Acarology 24, no. 1 (January 29, 2019): 158. http://dx.doi.org/10.11158/saa.24.1.12.
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Ticks are exclusive blood-feeding parasites that are of medical and veterinary importance. Ticks are also host for several maternally inherited symbiotic bacteria that are non-pathogenic bacteria and have potential roles in tick biology and the transmission of co-infecting pathogens. In order to gain a comprehensive view of these symbionts in ticks, we overviewed their incidence and biological importance within ticks based on available data. The symbionts in ticks are diverse, and their incidence and frequency vary across different tick species and different geographical populations of the same species. In some cases, symbionts of Coxiella, Francisella and Rickettsia genera may provide tick hosts essential nutrients absent from the exclusive food source of ticks and exhibit mutualistic relationships with their hosts. However, most symbionts are facultative and affect the biological phenotypes of their tick hosts through various ways. For some strains of Coxiella and Francisella, advanced genomic data and phylogenetic investigations have revealed their interactions with hosts and their evolutionary transitions of pathogenic and mutualistic forms. These findings are valuable for understanding tick-symbiont associations, and may help to develop new strategies to control ticks and tick-borne diseases.
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Lustig, Gila, Christopher M. Ryan, W. Evan Secor, and Patricia J. Johnson. "Trichomonas vaginalis Contact-Dependent Cytolysis of Epithelial Cells." Infection and Immunity 81, no. 5 (February 19, 2013): 1411–19. http://dx.doi.org/10.1128/iai.01244-12.
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ABSTRACTTrichomonas vaginalisis an extracellular protozoan parasite that binds to the epithelium of the human urogenital tract during infection. In this study, we examined the propensities of 26T. vaginalisstrains to bind to and lyse prostate (BPH-1) and ectocervical (Ect1) epithelium and to lyse red blood cells (RBCs). We found that only three of the strains had a statistically significant preference for either BPH-1 (MSA1103) or Ect1 (LA1 and MSA1123). Overall, we observed that levels of adherence are highly variable among strains, with a 12-fold range of adherence on Ect1 cells and a 45-fold range on BPH-1 cells. Cytolysis levels displayed even greater variability, from no detectable cytolysis to 80% or 90% cytolysis of Ect1 and BPH-1, respectively. Levels of adherence and cytolysis correlate for weakly adherent/cytolytic strains, and a threshold of attachment was found to be necessary to trigger cytolysis; however, this threshold can be reached without inducing cytolysis. Furthermore, cytolysis was completely blocked when we prevented attachment of the parasites to host cells while allowing soluble factors complete access. We demonstrate that hemolysis was a rare trait, with only 4 of the 26 strains capable of lysing >20% RBCs with a 1:30 parasite/RBC ratio. Hemolysis also did not correlate with adherence to or cytolysis of either male (BPH-1)- or female (Ect1)-derived epithelial cell lines. Our results reveal that despite a broad range of pathogenic properties among differentT. vaginalisstrains, all strains show strict contact-dependent cytolysis.
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AUSTEN, JILL M., SIMON A. REID, DERRICK R. ROBINSON, JAMES A. FRIEND, WILLIAM G. F. DITCHAM, PETER J. IRWIN, and UNA RYAN. "Investigation of the morphological diversity of the potentially zoonoticTrypanosoma copemaniin quokkas and Gilbert's potoroos." Parasitology 142, no. 11 (July 10, 2015): 1443–52. http://dx.doi.org/10.1017/s0031182015000785.
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SUMMARYTrypanosomes are blood-borne parasites that can cause severe disease in both humans and animals, yet little is known of the pathogenicity and life-cycles of trypanosomes in native Australian mammals.Trypanosoma copemaniis known to be infective to a variety of Australian marsupials and has recently been shown to be potentially zoonotic as it is resistant to normal human serum. In the present study,in vivoandin vitroexamination of blood and cultures from Australian marsupials was conducted using light microscopy, immunofluorescence, scanning electron microscopy and fluorescencein situhybridization. Promastigote, sphaeromastigote and amastigote life-cycle stages were detectedin vivoandin vitro. Novel trypanosome-like stages were also detected bothin vivoandin vitrorepresenting an oval stage, an extremely thin stage, an adherent stage and a tiny round stage. The tiny round and adherent stages appeared to adhere to erythrocytes causing potential haematological damage with clinical effects similar to haemolytic anaemia. The present study shows for the first time that trypomastigotes are not the only life-cycle stages circulating within the blood stream of trypanosome infected Australian native marsupials and provides insights into possible pathogenic mechanisms of this potentially zoonotic trypanosome species.
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Rawangchue, Thanakorn, and Sivapong Sungpradit. "Clinicopathological and molecular profiles of Babesia vogeli infection and Ehrlichia canis coinfection." July-2020 13, no. 7 (2020): 1294–302. http://dx.doi.org/10.14202/vetworld.2020.1294-1302.
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Background and Aim: Canine babesiosis, a tick-borne parasitic disease, is caused by the hemoprotozoa, Babesia vogeli, and Babesia gibsoni. Infection with these parasites, which is endemic globally, leads to life-threatening immunosuppression in dogs. The merozoites invade the red blood cells (RBCs) of infected dogs. Ehrlichia canis, an intracellular bacterium that infects monocytes, is transmitted by the same tick species (Rhipicephalus sanguineus) during blood consumption and coinfection with B. vogeli and E. canis has been reported. Although the hematology and biochemistry of canine babesiosis have been studied, more studies are needed to develop a better understanding of the hematobiochemical and molecular profiles associated with cases of single infection and coinfection of canine babesiosis in Thailand. This study aimed to investigate the hematological, biochemical, and molecular profiles of B. vogeli infection and E. canis coinfection. Materials and Methods: The study included 33 B. vogeli–positive blood samples and 11 E. canis–coinfected blood samples. To exclude coinfection with Hepatozoon canis and Anaplasma platys, only dogs with B. vogeli infection and B. vogeli–E. canis coinfection were included in the study. A multiplex polymerase chain reaction (PCR) assay was conducted to detect B. vogeli, E. canis, and H. canis, and a conventional PCR assay was conducted for the detection of A. platys. Besides, the PCR assay and sequencing, comprehensive data analysis was conducted, including a microscopic blood parasite examination and hematological and biochemical data analysis. Results: The comparison of the hematobiochemical data between the B. vogeli–positive and E. canis coinfection groups identified that there were statistically significant differences in the RBC parameters, including RBC count, hemoglobin concentration, hematocrit, and RBC distribution width (p=0.001). Neither B. vogeli infection nor coinfection with E. canis was associated with the sex, breed, recorded clinical signs, geographic origin of the dog and also B. vogeli 18S rRNA gene sequencing results. Conclusion: Coinfection with E. canis increased the severity of babesiosis. The pathogenic mechanisms underlying this infection, such as destruction of RBCs, require further investigation. This study may enhance diagnosis, treatment, and prevention of canine babesiosis.
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Horb, K. O. "Biochemical parameters of blood serum of dogs for ctenocephalidosis." Scientific Messenger of LNU of Veterinary Medicine and Biotechnologies 22, no. 97 (May 7, 2020): 3–6. http://dx.doi.org/10.32718/nvlvet9701.
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One of the most common ectoparasitic diseases of domestic carnivorous animals is ctenocephalidosis caused by fleas of the genus Ctenocephalides. The peculiarity of this invasion is a chronic course associated with the constant attack of parasitic insects on the animal, accompanied by severe itching, the occurrence of alopecia, the development of eczema, dermatitis and the subsequent introduction of pathogenic microflora into the damaged tissue. The aim of the study was to investigate the effect of fleas of the genus Ctenocephalides on the biochemical parameters of the blood serum of invaded dogs. Three groups of animals were formed: a control (clinically healthy dog) and two experimental animals (infected by the parasitic insect Ctenocephalides spp.) with different intrusion rates. In blood serum determined: the content of total protein, albumin, total bilirubin, creatinine, urea, glucose, cholesterol, phosphorus, potassium, calcium, magnesium, alanine aminotransferase activity, aspartate aminotransferase, alkaline phosphate. Conducted studies found that rates the intensity of infestation significantly influence the changes that occur in blood serum infested dogs. The intensity of ctenocephalidosic infestation of up to 15 specimens of fleas in the animal in their blood serum showed a significant decrease in albumin content (by 22.37 %) compared to that in clinically healthy dogs. The intensities of xenophalphalous infestation of 16–47 specimens of fleas per animal in the serum of the infected animals showed a significant decrease in albumin (by 29.28 %), glucose (by 25.29 %), and cholesterol (by 35.59 %) relative to similar indicators clinically healthy animals. At the same time in the serum of the infested dogs the content of total bilirubin (by 15.73 %), as well as the activity of alanine aminotransferase (1.4 times), aspartate aminotransferase (1.4 times) and alkaline phosphatase (2 times). The results of the experimental data extend the already existing data on the pathogenesis of fleas parasites in dogs, and will also allow the effective treatment of diseased animals.
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Olaniyan, Mathew Folaranmi. "MOSQUITO-BORNE PARASITES IN PATIENTS NEWLY INFECTED WITH HIV IN RELATIONSHIP WITH CD4 COUNT AND TNF ΑLPHA." Journal of Vocational Health Studies 5, no. 1 (July 31, 2021): 58. http://dx.doi.org/10.20473/jvhs.v5.i1.2021.58-64.
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Background: Mosquito-borne parasites include the pathogenic protozoa and helminths that are transmitted by the insect vector which may co-infect with other organisms to elicit an immune response. Purpose: To determine the frequency of mosquito-borne parasites in patients newly infected with HIV in relationship with CD4 count and TNFα. Method: Thirty-one (31; aged 15-32 years; male-12; female-19) newly diagnosed HIV positive patients and fifty (50) age-matched HIV negative volunteers were recruited as a control subject for this study. All subjects were negative to anti-HCV/HBsAg ELISA, Plasmodium, Acid-Fast Bacilli (AFB) tests and the control subjects were also negative to HIVP24 Ag-Ab ELISA, Plasmodium spp. and Wuchereria bancrofti microscopy. Venous blood including Night blood samples and sputum samples were obtained from the participants for CD4 count by cyflowmetry, TNFα, HIVP24Ag-Ab, anti-HCV, HBsAg by ELISA and microscopic identification by Giemsa staining while Sputum sample was used for Ziehl Neelsen staining to demonstrate Acid Fast Bacilli (AFB). Result: A lower frequency of 25.8% (Rajan, 2008) Plasmodium spp. and 6.5% (James et al., 2015) W. bancrofti was obtained in newly infected HIV patients compared with 32% (Zeitlmann et al., 2001) Plasmodium spp. and 8% (WHO, 2019) W. bancrofti obtained in the non-HIV infected control subjects. Showed a significant decrease in CD4 count and increase in plasma TNFα in both HIV mono-infection and coinfection with Plasmodium spp. and W. bancrofti compared with the results obtained in the non-HIV infected control subjects (p<0.05) and the results obtained in the newly infected HIV patients without Plasmodium spp. and W. coinfection (p<0.05). Conclusion: There was a significant increase in plasma TNFα and a decrease in CD4 count in both HIV mono-infection and coinfection with Plasmodium spp. and W. bancrofti while a lower frequency of Plasmodium spp. and W. bancrofti was obtained in newly infected HIV patients compared with the results obtained in the non-HIV infected control subjects.
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Promrangsee, Chulaluk, Pathamet Khositharattanakool, Puckavadee Somwang, Sakone Sunantaraporn, Atchara Phumee, Kanok Preativatanyou, Apiwat Tawatsin, Narisa Brownell, and Padet Siriyasatien. "The Prevalence of Bartonella Bacteria in Cattle Lice Collected from Three Provinces of Thailand." Insects 10, no. 6 (May 28, 2019): 152. http://dx.doi.org/10.3390/insects10060152.
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Cattle lice are obligatory blood-sucking parasites, which is the cause of animal health problems worldwide. Recently, several studies have revealed that pathogenic bacteria could be found in cattle lice, and it can act as a potential vector for transmitting louse-borne diseases. However, the cattle lice and their pathogenic bacteria in Thailand have never been evaluated. In the present study, we aim to determine the presence of bacterial pathogens in cattle lice collected from three localities of Thailand. Total genomic DNA was extracted from 109 cattle louse samples and the Polymerase Chain Reaction (PCR) of 18S rRNA was developed to identify the cattle louse. Moreover, PCR was used for screening Bartonella spp., Acinetobacter spp., and Rickettsia spp. in cattle louse samples. The positive PCR products were cloned and sequenced. The phylogenetic tree based on the partial 18S rRNA sequences demonstrated that cattle lice species in this study are classified into two groups according to reference sequences; Haematopinus quadripertusus and Haematopinus spp. closely related to H. tuberculatus. The pathogen detection revealed that Bartonella spp. DNA of gltA and rpoB were detected in 25 of 109 samples (22.93%) both egg and adult stages, whereas Acinetobacter spp. and Rickettsia spp. were not detected in all cattle lice DNA samples. The gltA and rpoB sequences showed that the Bartonella spp. DNA was found in both H. quadripertusus and Haematopinus spp. closely related to H. tuberculatus. This study is the first report of the Bartonella spp. detected in cattle lice from Thailand. The finding obtained from this study could be used to determine whether the cattle lice can serve as a potential vector to transmit these pathogenic bacteria among cattle and may affect animal to human health.
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Ibrahim, Mahamat Alhadj Moussa, Judith Sophie Weber, Sen Claudine Henriette Ngomtcho, Djoukzoumka Signaboubo, Petra Berger, Hassane Mahamat Hassane, and Sørge Kelm. "Diversity of trypanosomes in humans and cattle in the HAT foci Mandoul and Maro, Southern Chad—A matter of concern for zoonotic potential?" PLOS Neglected Tropical Diseases 15, no. 6 (June 9, 2021): e0009323. http://dx.doi.org/10.1371/journal.pntd.0009323.
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Background African trypanosomes are parasites mainly transmitted by tsetse flies. They cause trypanosomiasis in humans (HAT) and animals (AAT). In Chad, HAT/AAT are endemic. This study investigates the diversity and distribution of trypanosomes in Mandoul, an isolated area where a tsetse control campaign is ongoing, and Maro, an area bordering the Central African Republic (CAR) where the control had not started. Methods 717 human and 540 cattle blood samples were collected, and 177 tsetse flies were caught. Trypanosomal DNA was detected using PCR targeting internal transcribed spacer 1 (ITS1) and glycosomal glyceraldehyde-3 phosphate dehydrogenase (gGAPDH), followed by amplicon sequencing. Results Trypanosomal DNA was identified in 14 human samples, 227 cattle samples, and in tsetse. Besides T. b. gambiense, T. congolense was detected in human in Maro. In Mandoul, DNA from an unknown Trypanosoma sp.-129-H was detected in a human with a history of a cured HAT infection and persisting symptoms. In cattle and tsetse samples from Maro, T. godfreyi and T. grayi were detected besides the known animal pathogens, in addition to T. theileri (in cattle) and T. simiae (in tsetse). Furthermore, in Maro, evidence for additional unknown trypanosomes was obtained in tsetse. In contrast, in the Mandoul area, only T. theileri, T. simiae, and T. vivax DNA was identified in cattle. Genetic diversity was most prominent in T. vivax and T. theileri. Conclusion Tsetse control activities in Mandoul reduced the tsetse population and thus the pathogenic parasites. Nevertheless, T. theileri, T. vivax, and T. simiae are frequent in cattle suggesting transmission by other insect vectors. In contrast, in Maro, transhumance to/from Central African Republic and no tsetse control may have led to the high diversity and frequency of trypanosomes observed including HAT/AAT pathogenic species. Active HAT infections stress the need to enforce monitoring and control campaigns. Additionally, the diverse trypanosome species in humans and cattle indicate the necessity to investigate the infectivity of the unknown trypanosomes regarding their zoonotic potential. Finally, this study should be widened to other trypanosome hosts to capture the whole diversity of circulating trypanosomes.
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Herwaldt, Barbara L. "Laboratory-Acquired Parasitic Infections from Accidental Exposures." Clinical Microbiology Reviews 14, no. 4 (October 1, 2001): 659–88. http://dx.doi.org/10.1128/cmr.14.3.659-688.2001.
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SUMMARY Parasitic diseases are receiving increasing attention in developed countries in part because of their importance in travelers, immigrants, and immunocompromised persons. The main purpose of this review is to educate laboratorians, the primary readership, and health care workers, the secondary readership, about the potential hazards of handling specimens that contain viable parasites and about the diseases that can result. This is accomplished partly through discussion of the occupationally acquired cases of parasitic infections that have been reported, focusing for each case on the type of accident that resulted in infection, the length of the incubation period, the clinical manifestations that developed, and the means by which infection was detected. The article focuses on the cases of infection with the protozoa that cause leishmaniasis, malaria, toxoplasmosis, Chagas' disease (American trypanosomiasis), and African trypanosomiasis. Data about 164 such cases are discussed, as are data about cases caused by intestinal protozoa and by helminths. Of the 105 case-patients infected with blood and tissue protozoa who either recalled an accident or for whom the likely route of transmission could be presumed, 47 (44.8%) had percutaneous exposure via a contaminated needle or other sharp object. Some accidents were directly linked to poor laboratory practices (e.g., recapping a needle or working barehanded). To decrease the likelihood of accidental exposures, persons who could be exposed to pathogenic parasites must be thoroughly instructed in safety precautions before they begin to work and through ongoing training programs. Protocols should be provided for handling specimens that could contain viable organisms, using protective clothing and equipment, dealing with spills of infectious organisms, and responding to accidents. Special care should be exercised when using needles and other sharp objects.
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Coetzer, Theresa L., and Sonja B. Lauterbach. "Safety of Total Therapy III for Newly Diagnosed Multiple Myeloma: Preliminary Analysis of 62 Consecutive Patients. Safety of Total Therapy III for Newly Diagnosed Multiple Myeloma: Preliminary Analysis of 62 Consecutive Patients." Blood 104, no. 11 (November 16, 2004): 1582. http://dx.doi.org/10.1182/blood.v104.11.1582.1582.
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Abstract Malaria is one of the world’s major health problems, causing millions of deaths every year, primarily in Africa. The disease is caused by Plasmodium parasites, which invade and destroy human erythrocytes. Of the four species infecting humans, Plasmodium falciparum is responsible for the greatest morbidity and mortality burden. The erythrocyte membrane plays a vital role in all aspects of the pathogenic phase of the parasite’s life cycle and the protein-protein interactions between host and parasite are a key focus of research. Spectrin is the main structural protein in the erythrocyte membrane skeleton and phage-display technology was used to probe the interaction between P falciparum peptide fragments and human erythrocyte spectrin. A phage-display library was constructed by isolating mRNA from P falciparum strain FCR-3, which was reverse transcribed using two-base anchored oligodT primers. Linkers facilitating directional cloning were added to the cDNA, followed by insertion into a gene encoding the 10B capsid protein of the T7 bacteriophage vector. The vector was packaged into viral particles and the library amplified using Escherichia coli as a host. The presence and size of inserts were determined by PCR amplification with T7 bacteriophage vector arm specific primers. Human erythrocyte membranes were prepared from whole blood by hypotonic lysis and spectrin was extracted with a low ionic strength buffer and purified by size exclusion chromatography. The protein was biotinylated, immobilized on streptavidin-coated magnetic beads and biopanned against the phage library. Bound phage were eluted and amplified in E coli for three additional rounds of biopanning to eliminate non-specific protein-protein interactions. The P falciparum cDNA inserts of interacting phage were sequenced and compared to the PlasmoDB database. One of the sequences was identified as a putative aminopeptidase (PFI1570c), which has a 30.7% homology to a human aspartyl aminopeptidase, an enzyme catalysing the release of N-terminal amino acids from a peptide. The parasite protein contains a putative transmembrane domain at the C terminal end and is larger than the human form, with an estimated molecular weight of 65 kD. Several features that are critical for enzyme activity are conserved in the P falciparum aminopeptidase. These include twelve amino acids (four histidine, three glutamic acid and five aspartic acid residues), which are involved in the binding of catalytic zinc ions in the active site, as well as a putative N-myristoylation site and phosphorylation sites for casein kinase II and protein kinase C. Interestingly, the peptide fragment that bound to spectrin in the initial phage display screening, corresponds to a 33 amino acid fragment that is not found in the human aspartyl aminopeptidase. This suggests an evolutionary development of the parasite that allows the protease to bind to human spectrin. Mass spectrometry and microarray data from the PlasmoDB database indicate that the protein is present at the erythrocyte membrane and is expressed in all the developmental stages of the parasite’s erythrocytic life cycle. During the trophozoite stage the parasite modifies the erythrocyte membrane to allow transport of nutrients and waste products. The aminopeptidase could cleave spectrin and destabilise the membrane skeleton to facilitate the insertion of parasite protein channels during development. It may also play a role in proteolysis of the skeleton to enable the release of schizonts from infected erythrocytes.
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Wang, Xiaohui, Wenbin Zou, Hailiang Yu, Yuxin Lin, Guojun Dai, Tao Zhang, Genxi Zhang, Kaizhou Xie, Jinyu Wang, and Huiqiang Shi. "RNA Sequencing Analysis of Chicken Cecum Tissues Following Eimeria tenella Infection in Vivo." Genes 10, no. 6 (May 31, 2019): 420. http://dx.doi.org/10.3390/genes10060420.
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Eimeria tenella (E. tenella) is one of the most frequent and pathogenic species of protozoan parasites of the genus Eimeria that exclusively occupies the cecum, exerting a high economic impact on the poultry industry. To investigate differentially expressed genes (DEGs) in the cecal tissue of Jinghai yellow chickens infected with E. tenella, the molecular response process, and the immune response mechanism during coccidial infection, RNA-seq was used to analyze the cecal tissues of an E. tenella infection group (JS) and an uninfected group (JC) on the seventh day post-infection. The DEGs were screened by functional and pathway enrichment analyses. The results indicated that there were 5477 DEGs (p-value < 0.05) between the JS and the JC groups, of which 2942 were upregulated, and 2535 were downregulated. GO analysis indicated that the top 30 significantly enriched GO terms mainly involved signal transduction, angiogenesis, inflammatory response, and blood vessel development. KEGG analysis revealed that the top significantly enriched signaling pathways included focal adhesion, extracellular matrix–receptor interaction, and peroxisome proliferator-activated receptor. The key DEGs in these pathways included ANGPTL4, ACSL5, VEGFC, MAPK10, and CD44. These genes play an important role in the infection of E. tenella. This study further enhances our understanding of the molecular mechanism of E. tenella infection in chickens.
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Davis, Mindy I., Stephen L. Patrick, Walker M. Blanding, Varun Dwivedi, Jimmy Suryadi, Jennifer E. Golden, Nathan P. Coussens, et al. "Identification of Novel Plasmodium falciparum Hexokinase Inhibitors with Antiparasitic Activity." Antimicrobial Agents and Chemotherapy 60, no. 10 (July 25, 2016): 6023–33. http://dx.doi.org/10.1128/aac.00914-16.
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ABSTRACTPlasmodium falciparum, the deadliest species of malaria parasites, is dependent on glycolysis for the generation of ATP during the pathogenic red blood cell stage. Hexokinase (HK) catalyzes the first step in glycolysis, transferring the γ-phosphoryl group of ATP to glucose to yield glucose-6-phosphate. Here, we describe the validation of a high-throughput assay for screening small-molecule collections to identify inhibitors of theP. falciparumHK (PfHK). The assay, which employed an ADP-Glo reporter system in a 1,536-well-plate format, was robust with a signal-to-background ratio of 3.4 ± 1.2, a coefficient of variation of 6.8% ± 2.9%, and a Z′-factor of 0.75 ± 0.08. Using this assay, we screened 57,654 molecules from multiple small-molecule collections. Confirmed hits were resolved into four clusters on the basis of structural relatedness. Multiple singleton hits were also identified. The most potent inhibitors had 50% inhibitory concentrations as low as ∼1 μM, and several were found to have low-micromolar 50% effective concentrations against asexual intraerythrocytic-stageP. falciparumparasites. These molecules additionally demonstrated limited toxicity against a panel of mammalian cells. The identification of PfHK inhibitors with antiparasitic activity using this validated screening assay is encouraging, as it justifies additional HTS campaigns with more structurally amenable libraries for the identification of potential leads for future therapeutic development.
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Cao, Huan, Heather J. Wassall, Megan A. Forrester, Lindsay S. Hall, Heather M. Wilson, Jenna Shepherd, Bhinal Patel, et al. "Hemoglobin S Induces Exposure of Red Blood Cell Membrane Skeleton Microdomains Bearing Mannose That Stimulate Phagocytosis By Macrophages: A Molecular Basis for Hemolysis in Sickle Cell Disease but Protection Against Plasmodium Falciparum malaria." Blood 132, Supplement 1 (November 29, 2018): 3642. http://dx.doi.org/10.1182/blood-2018-99-117290.
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Abstract Heterozygosity for Hemoglobin (Hb) S, sickle cell trait (SCT), affects over 40 million people and confers resistance to severe infection by Plasmodium falciparum. Homozygosity for HbS, or compound heterozygosity with certain other alleles of Hb, affects over 4 million individuals and causes sickle cell disease (SCD). Hemolytic anaemia is a prominent feature of SCD and is mainly extravascular, mediated by hepatic and splenic macrophages. No ligands for this process have been identified. As many macrophage phagocytic receptors recognise carbohydrates, we surveyed surface glycan expression by sickle cells using a panel of 8 lectins and flow cytometry. Most glycans were similar to those of healthy red blood cells (RBC), except much higher expression of terminal mannose. We investigated the structural basis for these residues using glycomic mass spectroscopy, which showed them to be N-linked high (Man5-9GlcNAc2) mannoses, a surprising conclusion as these are usually intermediates in the formation of complex glycans and not displayed on cell surfaces. High resolution microscopy revealed the mannose residues to be carried in discrete microdomains on the surfaces of sickle cells. These structures were absent on the surfaces of healthy RBC, instead being present in the membrane skeleton under the cell surface. Lectin blots and immunoprecipitation showed the mannoses to co-migrate predominantly with spectrin. We showed these mannose-bearing structures were able to stimulate phagocytosis of RBC by using a peripheral blood derived macrophage uptake assay. Sickle RBC were taken up at high rates compared to healthy RBC and this could be inhibited by congeners of mannose. We identified the importance of a cognate ligand (CD206: the mannose receptor) using blocking antibodies and knockdown of CD206 expression using siRNA. The in vivo and pathogenic relevance of mannose exposure was investigated by taking advantage of the heterogeneity of hemolysis in SCD. RBC with SCD (n=94), SCT (n=57) and healthy individuals (n=54) were assayed for mannose exposure by flow cytometry. SCT and healthy RBC showed no mannose exposure but high levels were found on HbSS RBC (p<0.0001). Co-incident inheritance of HbSS with higher HbF values and alleles encoding alpha-thalassaemia resulted in lower surface mannose values. Overall, markers of hemolysis (RBC count, haemoglobin, reticulocyte count) correlated well with mannose exposure (Spearman correlation coefficients -0.68, -0.40, 0.37; p=0.0001, 0.0032, 0.0063 respectively). Plasma LDH is a marker of intravascular hemolysis and correlated with overall hemolysis within SCD (r=-0.25, p=0.016), but not mannose exposure (r=0.14, p=0.19). Thus mannose exposure correlated only with extravascular hemolysis. Identification of a ligand pair mediating rapid clearance of sickle cells raised the possibility that they also mediate enhanced clearance of SCT RBC infected by malarial parasites. Indeed, P. falciparum cultures induced mannose expression at the pigmented trophozoite and schizont stages in infected HbAA RBCs, at levels corresponding to mild hemolysis in SCD. Mannose expression in infected HbAS RBCs was even higher, with levels corresponding to severe hemolysis in SCD. Infection with P. falciparum and selection for HbS arose only recently in human evolution, raising the question of what the physiological triggers for this mechanism are. Infection with malarial parasites causes oxidative stress. We therefore subjected healthy RBC to copper sulphate, which resulted in surface mannose exposure as well as uptake by macrophages. Oxidized SCT RBC displayed more mannose than oxidized healthy RBC. Thus, we have identified a new cell surface 'eat me' signalling mechanism that allows inspecting macrophages to engage with the rigid membrane skeleton and phagocytose the mannose displaying cell. The mechanism is stimulated by HbS: when present in high concentrations, the mechanism is activated constitutively, resulting in sickle cell anaemia. Heterozygosity for HbS is insufficient by itself to trigger mannose exposure. However, the mechanism is primed so that oxidative stress associated with infection by P. falciparum causes greater mannose display, increased parasitized cell clearance and protection against severe malaria. These findings should allow the design of inhibitors of sickle cell haemolysis and inducers of protection against malaria. Disclosures Cao: University of Aberdeen: Patents & Royalties. Barker:University of Aberdeen: Patents & Royalties. Vickers:University of Aberdeen: Patents & Royalties; GSK: Equity Ownership.
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Afolabi, Olajide Joseph, A. Aremo, Oluwabunmi H, I. Itansanmi, and Anuoluwa I. "Malaria, hepatitis B and HIV /AIDS, and their co-infection among Patients Visiting Health Centres in Akure, Nigeria." Journal of Biomedicine and Translational Research 4, no. 2 (December 31, 2018): 22. http://dx.doi.org/10.14710/jbtr.v4i2.3457.
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Co-infection is the simultaneous infection of host by multiple pathogenic species, which may co-exist together or not. In this study, the co-infection of malaria, HIV/AIDS and hepatitis B was investigated, using four different locations in Akure, Ondo State. Blood samples were aseptically collected from the left thumbs of 500 respondents using sterile lancets. Thin and thick smear of the blood samples were observed for malaria parasites using X100 magnification of the light microscope. Hepatitis B and HIV/AIDS were tested using diagnostic test kits. The results show that highest prevalence of malaria was observed in Oba-Ile (82.09%) among age group 31-40 years (92.72%). The lowest prevalence was found in Ala-Ajagbusi (73.17%) among age group 21-30 years (70.03%). Highest prevalence of hepatitis (7.06%) was observed in Orita-Obele while the lowest prevalence was observed in Ala- Ajagbusi (4.88%). HIV/AIDS infection was found Orita-Obele (1.76%, n=3) and Ala-Ajagbusi (2.44%, n=2). The results further show that all the individuals that tested positive to hepatitis B virus and HIV also tested positive to malaria. Also, 3 of the 5 individuals infected with HIV/AIDS tested positive to hepatitis B virus. Similarly, malaria, hepatitis B virus and HIV cohabit in 2 individuals; 1 in age group 21-30 years and 1 in age group 31-40 years. Coinfection of malaria with hepatitis and HIV/AIDS suggests that malaria is an opportunistic infection among the hepatitis and AIDS patients. This calls for prompt malaria treatment among the immunocompromised patients. More so, there should be adequate and consistent public health advocacy programs, to enlighten the populace about malaria, hepatitis B and HIV/AIDS in order to completely mitigate the disease spread in the area.
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Agyemang, K., R. H. Dwinger, P. Jeannin, P. Leperre, A. S. Grieve, M. L. Bah, and D. A. Little. "Biological and economic impact of trypanosome infections on milk production in N'Dama cattle managed under village conditions in The Gambia." Animal Science 50, no. 3 (June 1990): 383–89. http://dx.doi.org/10.1017/s0003356100004864.
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ABSTRACTOver a 3-year period, productivity characteristics and criteria of trypanosomiasis incidence and severity have been monitored by monthly examination of individual N'Dama cattle in villages in The Gambia. From this database, 60 lactating cows in which Trypanosoma congolense or T. vivax had been detected on blood examination (group 1) were compared with 50 cows which had not been found infected with trypanosomes during the monitoring period (group 2). The latter were selected on the basis of comparability of age and stage of lactation to those of group 1 for examining the effect of trypanosome infections on the quantity of milk extracted for human consumption, and on the growth of their sucking calves. Data from a 6- to 7-month period were examined in the analysis.The quantity of daily milk extracted during the 1st month ot intection (group 1) decreased by proportionately 0·25 in comparison to the amount extracted during the preceding month when parasites were not detected. The corresponding figure in the uninfected controls (group 2) was 0·02. The mean daily milk extracted for human consumption from uninfected cows during a 6-month period was proportionately 0·26 higher than the mean for the infected cows. Growth rates of calves sucking infected and uninfected dams were similar.These observations indicate that infection with pathogenic trypanosomes of lactating N'Dama cattle causes a reduction in milk production.In economic terms, it was estimated that the decline in milk extracted for human consumption due to trypanosome infections amounted to an average of £1 per month per cow.
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Ojurongbe, Olusola, Roland I. Funwei, Tara J. Snyder, Najihah Aziz, Yi Li, Catherine O. Falade, and Bolaji N. Thomas. "Genetic Diversity of CD14 Promoter Gene Polymorphism (rs2569190) is Associated With Regulation of Malaria Parasitemia and Susceptibility to Plasmodium falciparum Infection." Infectious Diseases: Research and Treatment 10 (January 1, 2017): 117863361772678. http://dx.doi.org/10.1177/1178633617726781.
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CD14 is a multifunctional receptor expressed on many cell types and has been shown to mediate immune response resulting in the activation of an inflammatory cascade, with polymorphism of its promoter (rs2569190) found to be associated with susceptibility to several diseases. In malaria infection, the CD14 gene demonstrated a pathogenic profile in regulating experimental cerebral malaria, with reports of elevated levels of soluble CD14 in serum of patients but no definitive conclusion. We present a detailed analysis of genetic diversity of CD14 promoter gene (snp −159 C/T; rs2519190) polymorphism between a malaria-infected group and uninfected controls and its association with clinical parameters of disease. Genomic DNA samples obtained from 106 Plasmodium falciparum malaria–infected patients and 277 uninfected controls were elucidated with a polymerase chain reaction-restriction fragment length polymorphism (RFLP) assay. Our results show a significant diversity ( P = 3.32E−06) in the genotypic frequency (3.8% versus 22.4%) of the rs2569190 mutant variant between the malaria-infected group and controls, respectively. The mutant allele had the lowest frequency among the malaria-infected group demonstrating its necessity for infection. Mean parasitemia (parasites/μL of blood) was significantly regulated based on CD14 polymorphic profile (19 855 versus 37 041 versus 49 396 for homozygote mutants, heterozygotes, and homozygote wild type, respectively). Interestingly, we found no association between CD14 genetic variants with fever, age of patients, or anemia. How this affects disease severity between subregional and continental groups deserves further clarification, including extending these studies in a larger group and among severe and asymptomatic patients with malaria.
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Campeotto, Ivan, Adi Goldenzweig, Jack Davey, Lea Barfod, Jennifer M. Marshall, Sarah E. Silk, Katherine E. Wright, Simon J. Draper, Matthew K. Higgins, and Sarel J. Fleishman. "One-step design of a stable variant of the malaria invasion protein RH5 for use as a vaccine immunogen." Proceedings of the National Academy of Sciences 114, no. 5 (January 17, 2017): 998–1002. http://dx.doi.org/10.1073/pnas.1616903114.
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Many promising vaccine candidates from pathogenic viruses, bacteria, and parasites are unstable and cannot be produced cheaply for clinical use. For instance,Plasmodium falciparumreticulocyte-binding protein homolog 5 (PfRH5) is essential for erythrocyte invasion, is highly conserved among field isolates, and elicits antibodies that neutralize in vitro and protect in an animal model, making it a leading malaria vaccine candidate. However, functional RH5 is only expressible in eukaryotic systems and exhibits moderate temperature tolerance, limiting its usefulness in hot and low-income countries where malaria prevails. Current approaches to immunogen stabilization involve iterative application of rational or semirational design, random mutagenesis, and biochemical characterization. Typically, each round of optimization yields minor improvement in stability, and multiple rounds are required. In contrast, we developed a one-step design strategy using phylogenetic analysis and Rosetta atomistic calculations to design PfRH5 variants with improved packing and surface polarity. To demonstrate the robustness of this approach, we tested three PfRH5 designs, all of which showed improved stability relative to wild type. The best, bearing 18 mutations relative to PfRH5, expressed in a folded form in bacteria at >1 mg of protein per L of culture, and had 10–15 °C higher thermal tolerance than wild type, while also retaining ligand binding and immunogenic properties indistinguishable from wild type, proving its value as an immunogen for a future generation of vaccines against the malaria blood stage. We envision that this efficient computational stability design methodology will also be used to enhance the biophysical properties of other recalcitrant vaccine candidates from emerging pathogens.
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Torianyk, I. I., O. M. Tymchenko, M. O. Ostapets, N. A. Chygyrynska, S. I. Pokhyl, I. A. Kostyria, and I. V. Sorokina. "Use of polymerase chain reaction in verification and differential diagnosis of babesiosis pathogens." Regulatory Mechanisms in Biosystems 11, no. 4 (November 17, 2020): 563–67. http://dx.doi.org/10.15421/022087.
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Today, Babesia is recognized as one of the most common blood parasites in the world, which in terms of the number of cases of invasion is second only to trypanosomes (the causative agent of African trypanosomiasis and Chagas’ disease). These microorganisms can cause parasitism in erythrocytes and hematopoietic organs. They cause an infectious process, the clinical course of which can vary from asymptomatic, subclinical, mild or moderate influenza-like forms – to severe progressive disease (fulminant form) with fatal outcome. Thus, the latter determines the significant burden of babesia for the leading branches of medicine, veterinary medicine and the economy as a whole. The presented work is devoted to the study of the prospects for verification of babesiosis causative agents by the polymerase chain reaction (PCR) method. Blood, erythrocyte suspension, homogenized tick-carriers of babesiosis, culture of Babesia spp. were used as research material (samples). In order to obtain an objective assessment, the PCR-diagnostics method was used in two formats – standard and multiplex (multi-primer). Multiple PCR testing of multiplex format using primers in model samples containing cells of different species of Babesia (B. microti, B. divergens, B. bovis, B. canis), allowed us to establish the level of reproducibility of the results of such studies, which ranged 94.6–96.4%, to determine the level of PCR sensitivity of the multiplex format for detection/identification of human pathogenic babesia (B. microti, B. divergens and B. venatorum). It is established that the advantages of the PCR-diagnostic method of babesiosis pathogens in the samples of the studied biomaterial were: speed of research (2–4 hours); high sensitivity, specificity, reproducibility of Babesia detection results, prospects of species identification, differentiation with apicomplex spores (Plasmodium falciparum, Toxoplasma). In view of the above, the PCR method is recommended for use in cases of persistent suspicion of babesiosis infection (in cases of negative results of microscopic/cytological studies, to identify asymptomatic, subclinical and chronic forms of babesiosis, verification of active invasion in seropositive individuals and for Babesia species and their differentiation).
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Bunn, H. Franklin. "The triumph of good over evil: protection by the sickle gene against malaria." Blood 121, no. 1 (January 3, 2013): 20–25. http://dx.doi.org/10.1182/blood-2012-08-449397.
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Abstract The mechanisms underlying Plasmodium falciparum resistance in persons with sickle trait have been under active investigation for more than a half century. This Perspective reviews progress in solving this challenging problem, including recent studies that have exploited the genomics and proteomics of the parasite. The formation of Hb S polymer in the parasitized AS RBC leads to impaired parasite growth and development along with enhanced clearance from the circulation and reduced deposition in deep postcapillary vascular beds. Enhanced generation of reactive oxygen species in sickled AS RBCs is a pathogenetic feature shared by parasitized thalassemic and G6PD-deficient RBCs, triggering abnormal topology of the RBC plasma membrane with decreased and disordered display of PfEMP-1, a P falciparum adhesion protein critical for endothelial adherence. A mouse model of Hb S confers host tolerance to P berghei, through inhibition of pathogenic CD8+ T cells and induction of heme oxygenase-1. An additional and apparently independent mode of protection is provided by the selective expression in AS RBCs of 2 species of microRNA that integrate into P falciparum mRNAs and inhibit translation and parasite growth.
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Autino, Beatrice, Yolanda Corbett, Francesco Castelli, and Donatella Taramelli. "PATHOGENESIS OF MALARIA IN TISSUES AND BLOOD." Mediterranean Journal of Hematology and Infectious Diseases 4, no. 1 (October 4, 2012): e2012061. http://dx.doi.org/10.4084/mjhid.2012.061.
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The clinical manifestations of severe malaria are several and occur in different anatomical sites. Both parasite- and host-related factors contribute to the pathogenicity of the severe forms of the disease. Cytoadherence of infected red blood cells to the vascular endothelium of different organs and rosetting are unique features of malaria parasites which are likely to contribute to the vascular damage and the consequent excessive inflammatory/immune response of the host. In addition to cerebral malaria or severe anaemia, which are quite common manifestation of severe malaria, clinical evidences of thrombocytopenia, acute respiratory distress syndrome (ARDS), liver and kidney disease, are reported. In primigravidae from endemic areas, life threatening placental malaria may also be present.In the following pages, some of the pathogenetic aspects will be briefly reviewed and then data on selected and less frequent manifestation of severe malaria, such as liver or renal failure or ARDS will be discussed
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Magrone, Thea, Manrico Magrone, and Emilio Jirillo. "Eosinophils, a Jack of All Trades in Immunity: Therapeutic Approaches for Correcting Their Functional Disorders." Endocrine, Metabolic & Immune Disorders - Drug Targets 20, no. 8 (October 15, 2020): 1166–81. http://dx.doi.org/10.2174/1871530320666200309094726.
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Background: Eosinophils are primitive myeloid cells derived from bonemarrow precursors and require the intervention of interleukin (IL)-5 for their survival and persistence in blood and tissues. Under steady-state conditions, they contribute to immune regulation and homeostasis. Under pathological circumstances, eosinophils are involved in host protection against parasites and participate in allergy and inflammation. Discussion: Mostly, in asthma, eosinophils provoke airway damage via the release of granule contents and IL-13 with mucus hypersecretion and differentiation of goblet cells. Then, tissue remodeling follows with the secretion of transforming growth factor-β. Eosinophils are able to kill helminth larvae acting as antigen-presenting cells with the involvement of T helper (h)-2 cells and subsequent antibody response. However, they also exert pro-worm activity with the production of suppressive cytokine (IL- 10 and IL-4) and inhibition of nitric oxide. Eosinophils may play a pathogenic role in the course of chronic and autoimmune disease, e.g., inflammatory bowel disease and eosinophilic gastroenteritis, regulating Th2 responses and promoting a profibrotic effect. In atopic dermatitis, eosinophils are commonly detected and may be associated with disease severity. In cutaneous spontaneous urticaria, eosinophils participate in the formation of wheals, tissue remodeling and modifications of vascular permeability. With regard to tumor growth, it seems that IgE can exert anti-neoplastic surveillance via mast cell and eosinophil-mediated cytotoxicity, the so-called allergo-oncology. From a therapeutic point of view, monoclonal antibodies directed against IL-5 or the IL-5 receptors have been shown to be very effective in patients with severe asthma. Finally, as an alternative treatment, polyphenols for their anti-inflammatory and anti-allergic activities seem to be effective in reducing serum IgE and eosinophil count in bronchoalveolar lavage in murine asthma. Conclusion: Eosinophils are cells endowed with multiple functions and their modulation with monoclonal antibodies and nutraceuticals may be effective in the treatment of chronic disease.
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Bahl, Suhani, Priya Mohan Babu, Florin Capatana, Ishrat Khan, Mohamed Adlan, and Lakdasa D. K. E. Premawardhana. "Sub-Acute Thyroiditis Presenting as Pyrexia of Uknown Origin." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A956. http://dx.doi.org/10.1210/jendso/bvab048.1953.
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Abstract Introduction: Pyrexia of unknown origin (PUO) is often a diagnostic challenge. Common causes currently reported include non-infectious inflammatory disorders (NIID) (30.6%), infections (23.1%), malignancy (10.7%) and miscellaneous (12.4%). However, 23.1% remain undiagnosed despite extensive investigations. Fever is a component of subacute thyroiditis (SAT) in 28-83% of subjects reported in the literature. But its presentation as a PUO is reported only in a handful of subjects. Case Presentation: A 71-year-old Asian male presented with evening fevers of 2-3 weeks duration. He had no accompanying sweats, cough, breathlessness, or weight loss. He had a past history of TB, polio, hydatid cyst and hypertension for which he was on treatment. He was a teetotaler. Several family members living in his native land had active TB and he visited them often. Clinical examination at initial presentation was unremarkable. He interrupted investigations to go back to Asia, and became unwell for over 6 weeks with evening fevers and sweating, a weight loss of over 7 kg, and a poor appetite. At this point he had no neck pain, palpitations or bowel abnormalities. Clinical examination continued to be normal upon his return to the UK and in the Endocrine Clinic. Investigations: Investigations were done to exclude (a) infections - There was no growth of pathogenic organisms in repeated blood, urine and sputum cultures. Screening tests for TB, hepatitis, and glandular fever were negative. Blood screens for malarial parasites, amoebic and Brucella serology, and stools examination and culture were also negative. Echocardiography was normal. (b) Malignancy - Urine Bence Jones proteins and serum protein electrophoresis were normal. Bone marrow examination was suggestive of Leishmaniasis but a PCR test excluded this diagnosis. Humoral markers of malignancy were negative. CT scans of the thorax, abdomen and pelvis were normal and did not show any evidence of visceral abnormalities (c) NIID - CRP 120, ESR 130, with blood tests consistent with iron deficiency. Autoimmune screening for dsDNA, ANA, ANCA were negative. Upon return to the UK a PET/CT scan showed the diffuse tracer uptake in both thyroid lobes and changes consistent with a large left lobe. Free thryroxine was 28pmol/l (reference range 9-19.1), and TSH was undetectable (<0.004 mU/l). Thyrotrophin receptor antibodies were negative. Management and conclusion He was given carbimazole initially but this was stopped as he became severely hypothyroid. This hypothyroidism persisted for several months even after stopping carbimazole but reversed spontaneously. He therefore had a biphasic pattern of thyroiditis typical of SAT. There are only 9 previous cases reported of SAT presenting as PUO. Although SAT is a rare cause of PUO, early thyroid testing and if necessary, functional thyroid imaging should be considered in subjects with PUO to confirm it.
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Loukas, Alex, and Paul Prociv. "Immune Responses in Hookworm Infections." Clinical Microbiology Reviews 14, no. 4 (October 1, 2001): 689–703. http://dx.doi.org/10.1128/cmr.14.4.689-703.2001.
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SUMMARY Hookworms infect perhaps one-fifth of the entire human population, yet little is known about their interaction with our immune system. The two major species are Necator americanus, which is adapted to tropical conditions, and Ancylostoma duodenale, which predominates in more temperate zones. While having many common features, they also differ in several key aspects of their biology. Host immune responses are triggered by larval invasion of the skin, larval migration through the circulation and lungs, and worm establishment in the intestine, where adult worms feed on blood and mucosa while injecting various molecules that facilitate feeding and modulate host protective responses. Despite repeated exposure, protective immunity does not seem to develop in humans, so that infections occur in all age groups (depending on exposure patterns) and tend to be prolonged. Responses to both larval and adult worms have a characteristic T-helper type 2 profile, with activated mast cells in the gut mucosa, elevated levels of circulating immunoglobulin E, and eosinoophilia in the peripheral blood and local tissues, features also characteristic of type I hypersensitivity reactions. The longevity of adult hookworms is determined probably more by parasite genetics than by host immunity. However, many of the proteins released by the parasites seem to have immunomodulatory activity, presumably for self-protection. Advances in molecular biotechnology enable the identification and characterization of increasing numbers of these parasite molecules and should enhance our detailed understanding of the protective and pathogenetic mechanisms in hookworm infections.
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Clift, Sarah J., Nicola E. Collins, Marinda C. Oosthuizen, Johan C. A. Steyl, John A. Lawrence, and Emily P. Mitchell. "The Pathology of Pathogenic Theileriosis in African Wild Artiodactyls." Veterinary Pathology 57, no. 1 (December 19, 2019): 24–48. http://dx.doi.org/10.1177/0300985819879443.
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The published literature on schizont-“transforming,” or pathogenic theileriosis, in African wild artiodactyls is dated and based on limited information. Here the authors review the taxonomy, diagnosis, epidemiology, hematology, pathology, and aspects of control in various species. Molecular studies based on 18S and 16S rRNA gene sequences have shown that African wild artiodactyls are commonly infected with diverse Theileria spp., as well as nontheilerial hemoprotozoa and rickettsia-like bacteria, and coinfections with pathogenic and nonpathogenic Theileria species are often recorded. Although theileriosis is still confusingly referred to as cytauxzoonosis in many species, the validity of a separate Cytauxzoon genus in artiodactyls is debated. The epidemiology of theileriosis is complex; the likelihood of fatal disease depends on the interplay of parasite, vertebrate host, tick vector, and environmental factors. Roan calves ( Hippotragus equinus) and stressed animals of all host species are more susceptible to fatal theileriosis. Even though regenerative anemia is common, peripheral blood piroplasm parasitemia does not correlate with disease severity. Other than anemia, common macroscopic lesions include icterus, hemorrhages (mucosal, serosal, and tissue), fluid effusions into body cavities, lung edema, and variably sized raised cream-colored foci of leukocyte infiltration in multiple organs. Histopathologic findings include vasocentric hyperproliferation and lysis of atypical leukocytes with associated intracellular schizonts, parenchymal necrosis, hemorrhage, thromboembolism, and edema. Immunophenotyping is required to establish the identity of the schizont-transformed leukocytes in wild ungulates. Throughout the review, we propose avenues for future research by comparing existing knowledge on selected aspects of theileriosis in domestic livestock with that in African wild artiodactyls.
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Sood, NK, LD Singla, RS Singh, and SK Uppal. " Association of Trypanosoma theileri with peritonitis in a pregnant cross-bred cow: a case report." Veterinární Medicína 56, No. 2 (March 4, 2011): 82–84. http://dx.doi.org/10.17221/1580-vetmed.
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This clinical case report deals with a very rare case of the detection of Trypanosoma theileri in the peritoneal fluid of a seven-year-old eight month pregnant cross-bred cow in fourth parity showing frank peritonitis. Peritoneal tab cytology revealed chronic active peritonitis and the presence of polymorphic T. theileri organisms. The parasite was also occasionally detected in blood smears. The protozoan, considered by and large non-pathogenic, has previously been detected in aberrant body sites, other than the peritoneal cavity. A perusal of the available literature indicates that this is the first report of this large stercorarrian trypanosome associated with peritonitis, which was characterized by infiltration of mononuclear cells and neutrophils, as well as a significant number of intact and degranulating eosinophils, not usually seen in protozoan infections.
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Nie, Catherine Q., Nicholas J. Bernard, Louis Schofield, and Diana S. Hansen. "CD4+ CD25+ Regulatory T Cells Suppress CD4+ T-Cell Function and Inhibit the Development of Plasmodium berghei-Specific TH1 Responses Involved in Cerebral Malaria Pathogenesis." Infection and Immunity 75, no. 5 (February 26, 2007): 2275–82. http://dx.doi.org/10.1128/iai.01783-06.
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ABSTRACT The infection of mice with Plasmodium berghei ANKA constitutes the best available mouse model for human Plasmodium falciparum-mediated cerebral malaria, a devastating neurological syndrome that kills nearly 2.5 million people every year. Experimental data suggest that cerebral disease results from the sequestration of parasitized erythrocytes within brain blood vessels, which is exacerbated by host proinflammatory responses mediated by cytokines and effector cells including T lymphocytes. Here, T cell responses to P. berghei ANKA were analyzed in cerebral malaria-resistant and -susceptible mouse strains. CD4+ T-cell proliferation and interleukin-2 (IL-2) production in response to parasite-specific and polyclonal stimuli were strongly inhibited in cerebral malaria-resistant mice. In vitro and in vivo depletion of CD4+ CD25+ regulatory T (Treg) cells significantly reversed the inhibition of CD4+ T-cell proliferation and IL-2 production, indicating that this cell population contributes to the suppression of T-cell function during malaria. Moreover, in vivo depletion of Treg cells prevented the development of parasite-specific TH1 cells involved in the induction of cerebral malaria during a secondary parasitic challenge, demonstrating a regulatory role for this cell population in the control of pathogenic responses leading to fatal disease.
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Bogema, D. R., A. T. Deutscher, S. Fell, D. Collins, G. J. Eamens, and C. Jenkins. "Development and Validation of a Quantitative PCR Assay Using Multiplexed Hydrolysis Probes for Detection and Quantification of Theileria orientalis Isolates and Differentiation of Clinically Relevant Subtypes." Journal of Clinical Microbiology 53, no. 3 (January 14, 2015): 941–50. http://dx.doi.org/10.1128/jcm.03387-14.
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Theileria orientalisis an emerging pathogen of cattle in Asia, Australia, and New Zealand. This organism is a vector-borne hemoprotozoan that causes clinical disease characterized by anemia, abortion, and death, as well as persistent subclinical infections. Molecular methods of diagnosis are preferred due to their sensitivity and utility in differentiating between pathogenic and apathogenic genotypes. Conventional PCR (cPCR) assays forT. orientalisdetection and typing are laborious and do not provide an estimate of parasite load. Current real-time PCR assays cannot differentiate between clinically relevant and benign genotypes or are only semiquantitative without a defined clinical threshold. Here, we developed and validated a hydrolysis probe quantitative PCR (qPCR) assay which universally detects and quantifiesT. orientalisand identifies the clinically associated Ikeda and Chitose genotypes (UIC assay). Comparison of the UIC assay results with previously validated universal and genotype-specific cPCR results demonstrated that qPCR detects and differentiatesT. orientaliswith high sensitivity and specificiy. Comparison of quantitative results based on percent parasitemia, determined via blood film analysis and packed cell volume (PCV) revealed significant positive and negative correlations, respectively. One-way analysis of variance (ANOVA) indicated that blood samples from animals with clinical signs of disease contained statistically higher concentrations ofT. orientalisDNA than animals with subclinical infections. We propose clinical thresholds to assist in classifying high-, moderate-, and low-level infections and describe how parasite load and the presence of the Ikeda and Chitose genotypes relate to disease.
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Ximénez, Cecilia, Enrique González, Miriam E. Nieves, Angélica Silva-Olivares, Mineko Shibayama, Silvia Galindo-Gómez, Jaime Escobar-Herrera, et al. "Entamoeba histolyticaandE. disparCalreticulin: Inhibition of Classical Complement Pathway and Differences in the Level of Expression in Amoebic Liver Abscess." BioMed Research International 2014 (2014): 1–10. http://dx.doi.org/10.1155/2014/127453.
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The role of calreticulin (CRT) in host-parasite interactions has recently become an important area of research. Information about the functions of calreticulin and its relevance to the physiology ofEntamoebaparasites is limited. The present work demonstrates that CRT of both pathogenicE. histolyticaand nonpathogenicE. disparspecies specifically interacted with human C1q inhibiting the activation of the classical complement pathway. Using recombinantEhCRT protein, we demonstrate that CRT interaction site and human C1q is located at the N-terminal region ofEhCRT. The immunofluorescence and confocal microscopy experiments show that CRT and human C1q colocalize in the cytoplasmic vesicles and near to the surface membrane of previously permeabilized trophozoites or are incubated with normal human serum which is known to destroy trophozoites. In the presence of peripheral mononuclear blood cells, the distribution ofEhCRT and C1q is clearly over the surface membrane of trophozoites. Nevertheless, the level of expression of CRTin situin lesions of amoebic liver abscess (ALA) in the hamster model is different in bothEntamoebaspecies; this molecule is expressed in higher levels inE. histolyticathan inE. dispar. This result suggests thatEhCRT may modulate some functions during the early moments of the host-parasite relationship.