Human Parasitic Infections Research Articles

High levels of circulating IL-10 in human malaria.

IL-10 is a monocyte/lymphocyte derived cytokine which has been shown to inhibit certain cellular immune responses such as delayed hypersensitivity. In particular, the production of tumour necrosis factor (TNF), IL-1 and IL-6, which are involved in malaria pathology, are strongly inhibited by IL-10. Accordingly, we examined whether IL-10 could be involved in a human acute parasitic infection such as Plasmodium falciparum malaria. Human IL-10 levels in plasma were determined by two-site ELISA method, taking care to avoid non-specific reactions due to autoantibodies. Fourteen cerebral, 11 severe, and 20 mild malaria cases had mean IL-10 levels of 2812, 2882 and 913 pg/ml, respectively, while 98% of healthy individuals had undetectable (less than 100 pg/ml) circulating IL-10. Thirteen of the 25 cerebral/severe cases had > 2000 pg/ml. In 11 hospitalized patients, circulating IL-10 levels were found to return to virtually normal levels 7 days after antimalarial chemotherapy when biological and clinical malaria features had disappeared (mean levels fell from 3880 to 333 pg/ml). Further studies are required to determine whether these elevated levels of IL-10 play a beneficial role by reducing the parasite-induced inflammatory response, or a detrimental one by decreasing the cellular immune responses.

Human Intestinal Parasite Infections In Ishiagu, A Lead Mining Area Of Abia State

A survey of intestinal parasite infections in a heavy metal (Pb) mining area of Abia State (Ishiagu) was carried out using both direct wet preparation and formal/ether concentration methods. A total512 individuals ranging from primary and secondary school children to adults were screened. Of the number sampled, 177 (34.67 %) had various intestinal parasites. The parasite prevalence were Ascaris lumbricoides (17.80 %), Hookworms (14.80%) Entamoeba histolyca (3.70 %) and Trichuris trichiura (2.3 %). Prevalence for maes (35.55 %) and females (33.47%) were not significantly different (P 51 years (27.02 %). This gave a significant age related infection (P Keywords : Parasites, Heavy metal mining, Stool specimens Animal Research International Vol. 3 (3) 2006 pp. 505-507

CT and MR Characteristics of Cerebral Sparganosis

Sparganosis is a rare parasitic infection in humans by a larval cestode of the genus Spirometra. Preoperative diagnosis of cerebral sparganosis in the past has been very difficult. Our objective was to evaluate the CT and MR features of cerebral sparganosis in order to make a definite diagnosis. We retrospectively reviewed 25 patients (13 male and 12 female; age range, 9-83 years) who proved to have cerebral sparganosis. Fifteen patients underwent MR imaging: 2 patients had CT scanning, and the remaining 8 had both CT and MR scanning. We focused on evaluating the imaging features on CT and MR. All patients showed edema and degeneration of cerebral white matter. All but 1 had a unilateral lesion. Twenty-two patients had ipsilateral ventricular dilation. The new finding was a tunnel sign, approximately 4 cm in length and 0.8 cm in width, column or fusiform shaped on postcontrast coronal and sagittal MR images (n = 10). Thirteen patients showed bead-like enhancement, but solitary ring enhancement was common on the CT images (n = 2). The wall of the ring and tunnel appeared isointense or slightly hyperintense on T2-weighted images. Punctate calcifications were seen in 6 patients on CT images but only in 3 patients on the MR images. Hemorrhage was seen in 4 patients on the MR images. An intact whitish, stringlike, living worm was found (n = 5). The most characteristic finding was a tunnel sign on postcontrast MR images. The most common finding was bead-shaped enhancement. MR is superior to CT in demonstrating the extent and number of lesions, except punctate calcifications. Combined with clinical data and enzyme-linked immunosorbent assay, the preoperative diagnosis of cerebral sparganosis could be established on MR imaging.

Parasite findings in archeological remains: Diagnosis and interpretation

Paleoparasitology has contributed to resolving the debate about the peopling of the Americas and determining the antiquity of human parasite infection. Hookworm (Ancylostomidae) and whipworm ( Trichuris trichiura) and other exclusive human intestinal parasites have been recorded in pre-Columbian America. These parasite species originated in pre-hominids and have accompanied humans across continents when people went out of Africa. However, for those human populations that crossed the Bering Land Bridge from Siberia to Alaska, cold climate conditions hampered parasite transmission. Alternative migration routes have been proposed to explain the presence of these parasites in pre-Columbian populations in the Americas. Other parasites were established in the New World long before humans entered the American continents. One such malady is Chagas disease. Chagas disease, caused by Trypanosoma cruzi, offers an example of how animals and humans have interacted in the past. Classical theory points to the origin and dispersion of human T. cruzi infection among Andean populations, starting with sedentary habits and animal domestication 6000 years ago. However, recent PCR results in mummified bodies outside the Andean region have challenged this theory. Pre-Columbian Brazilian mummies were found positive for T. cruzi infection, raising an alternative hypothesis on the antiquity of Chagas disease in the Americas. Paleoparasitology is a new tool to study past events, shedding light on human and other animal behavior, migration routes, diet, and other aspects of host–parasite environment evolution.

A multiplex PCR that discriminates between Trypanosoma brucei brucei and zoonotic T. b. rhodesiense

Two subspecies of Trypanosoma brucei s.l. co-exist within the animal populations of Eastern Africa; T. b. brucei a parasite which only infects livestock and wildlife and T. b. rhodesiense a zoonotic parasite which infects domestic livestock, wildlife, and which in humans, results in the disease known as Human African Trypanosomiasis (HAT) or sleeping sickness. In order to assess the risk posed to humans from HAT it is necessary to identify animals harbouring potentially human infective parasites. The multiplex PCR method described here permits differentiation of human and non-human infective parasites T. b. rhodesiense and T. b. brucei based on the presence or absence of the SRA gene (specific for East African T. b. rhodesiense), inclusion of GPI-PLC as an internal control indicates whether sufficient genomic material is present for detection of a single copy T. brucei gene in the PCR reaction.

Food-Borne Parasitic Diseases

It is obvious that the general status of parasitic infections in Korea has shown a marked decrease, particularly in soil-transmitted helminthic infections. However, food-borne parasitic infections are still regarded as the major parasitic diseases of medical importance in Korea. Generally, the parasitic infections may occur from the following sources: by contaminated soil, water, vegetable and fruits, and other animals as food containing the parasites at their immature infective stage, in association with a domestic or wild animal harboring the parasite, and an ectoparasite that transmits the parasite by blood sucking. Human food-borne parasitic infections result from the consumption of undercooked or raw fish, shellfish, snails, vertebrates, and water plants as a food. These infections are significantly related to human behavioral patterns based on socioeconomic and cultural conditions and are linked with the biological and physical environments. Most of food-borne parasitic infections are considered as all parasitic zoonoses to man and animals. To understand the current status of food-borne parasitic infections in Korea, the author presents the list of overall food-borne parasitic infections caused by protozoan infection (toxoplasmosis), trematode infections (clonorchiasis, metagonimiasis, and some intestinal trematodiases), nematode infections (anisakiasis and trichinosis), and others with a briefly reviewed.

Seroprevalence of Toxoplasma gondii antibodies in a healthy population from Slovakia

Background Toxoplasma gondii is a ubiquitous parasite of warm-blooded animals that causes one of the most common parasitic infections in humans. Toxoplasmosis is not a frequently reported disease and its prevalence is based on regional studies. Methods This prospective, cross-sectional study was conducted to evaluate the seroprevalence of T. gondii antibodies in a non-endemic area among 508 healthy individuals in Slovakia. ELISA was used to detect the levels of IgG, IgA, and IgM antibodies. Epidemiological factors and clinical symptoms associated with seropositivity were investigated using questionnaires. Results An IgG antibody prevalence of 24.2% (123/508) was found in the study population, while examination of specific IgA and IgM antibodies was negative. A significant increase in toxoplasmosis prevalence with increasing age was confirmed ( p = 0.001). There were no significant differences between genders or between inhabitants of rural and urban areas ( p = 0.079 and p = 0.291, respectively). An increased consumption of raw meat (40.7%) and raw vegetables or fruit (30.8%) was observed in serologically positive women. This difference between serologically positive and negative women was significant ( p = 0.042). A significant difference between men and women eating raw vegetables and fruit was also found ( p = 0.049). There was no difference in clinical symptoms between serologically positive and negative patients ( p = 0.658). Lymphadenopathy with or without other symptoms (influenza, arthralgia, ocular symptom, dermatosis), 40.7%, was the most common clinical symptom in seropositive patients. Conclusion An increased prevalence of T. gondii was observed in the age group over 40 years and in women who consume raw meat, vegetables, or fruit.

World Class Parasites: Vol. X, Schistosomiasis

This compendium of reviews on the human parasitic infection, schistosomiasis, is a timely and much-needed resource for both research investigators and clinical personnel in many scientific and medical fields. Schistosomiasis is a major global health problem that affects hundreds of millions of people. It has been called one of the great neglected diseases because of the relative lack of interest by the pharmaceutical industry in developing diagnostics, drugs, and vaccines for it. The parasites that cause this disease, several related species of blood flukes, are also fascinating subjects for biologic research because of their complexity, relatively long lifespan, and remarkable host-parasite biology. To paraphrase Daniel Colley, one of the editors: Analysis of this infection has contributed as much to our understanding of the human immune response and host parasite interactions as science has contributed to the control of the disease. What sets this book apart is its readability for audiences from diverse backgrounds. This is in large part due to the thoughtfulness the editors put into choosing authors and topics, and perhaps most importantly, the relative brevity of each chapter. This latter point cannot be overemphasized since many compendiums overwhelm the reader with lengthy and dense material. This book is, therefore, especially valuable as a resource for students, postdoctoral fellows, and first-time investigators in this field. One obvious conclusion that a reader new to the field will take away from this book is the diversity of research in this field. This reflects, as the editors note, a newfound intellectual energy born of the successful (albeit fledgling) applications of molecular genetic techniques to the study of the host-parasite relationship in schistosomiasis. At the same time, a shortcoming of the book is the relative lack of attention to the biochemistry of schistosomes, which is a key foundation for understanding how the parasite ticks and identifying new targets for chemotherapy. The work of investigators like John Dalton and Conor Caffrey on schistosome digestion of host proteins, for example, gets bare mention. This may be an inevitable consequence of the authors coming from a background of schistosome immunology, which is well represented in the book. Another shortcoming is probably inescapable. As a field like schistosomiasis research enters a period of rapid and exciting advances, it is difficult for a book to keep up with the most recently published work. For example, many insights into the host-parasite relationship are becoming clear from proteomics analysis by groups like that of Alan Wilson at the University of York. Perhaps this criticism is actually reflecting good news as the field is reenergized. Colley correctly points out that the key to the future of research on this disease, and new approaches to its control, lies in recruiting a new generation of scientists and clinicians with an interest in the disease. I have been struck by the number of graduate students and MD/PhD students who have expressed a renewed interest in schistosome research over the past year. Like Colley, I believe this reflects the exciting technologic advances and novel approaches to understand the biology of this fascinating organism that are beginning to show success. If we are right that a new generation of young scientists are testing the waters of schistosome research, this excellent compendium could not come at a better time.

Sensitive and Inexpensive Molecular Test for Falciparum Malaria: Detecting Plasmodium falciparum DNA Directly from Heat-Treated Blood by Loop-Mediated Isothermal Amplification,

Malaria is one of the most important parasitic infections in humans. A sensitive diagnostic test for malaria that could be applied at the community level could be useful in programs to control the disease. The aim of the present work was to develop a simple, inexpensive molecular test for Plasmodium falciparum. Blood was collected from controls (n = 100) and from patients diagnosed with falciparum malaria infection (n = 102), who were recruited to the study. Heat-treated blood samples were tested by a loop-mediated isothermal amplification (LAMP) assay for P. falciparum. Results were interpreted by a turbidity meter in real time or visually at the end of the assay. To evaluate the assay, DNA from these samples was purified and tested by PCR. Results from the LAMP and PCR assays were compared. The LAMP assay detected P. falciparum directly from heat-treated blood. The quantitative data from the assay correlated to the parasite counts obtained by blood-film microscopic analyses. When we used the PCR assay as the comparison method, the sensitivity and specificity of the LAMP assay were 95% and 99%, respectively. Unlike PCR, the LAMP assay does not require purified DNA for efficient DNA amplification, thereby reducing the cost and turnaround time for P. falciparum diagnosis. The assay requires only basic instruments, and assay positivity can be verified by visual inspection.

Evaluation of the antibody response to Anopheles salivary antigens as a potential marker of risk of malaria

The evaluation of human immune responses to arthropod bites may be a useful marker of exposure to vector-borne diseases, with applications to malaria, the most serious parasitic infection in humans. The specific antibody (Ab) IgG response to saliva obtained from Anopheles gambiae mosquitoes was evaluated in young children from an area of seasonal malaria transmission in Senegal. Specific IgG was higher in children who developed clinical Plasmodium falciparum malaria within the 3 months that followed than in those who did not (P<0.05), and it increased significantly (P<0.0001) with the level of Anopheles exposure, as evaluated by conventional entomological methods. These results suggest that evaluation of antisalivary Ab responses could be a useful approach for identifying a marker for the risk of malaria transmission.

New approaches in vaccine development for parasitic infections

Vaccines have had a tremendous impact on the control of infectious diseases. Not only are vaccines potentially the least expensive mechanism to combat infectious diseases, under optimal conditions, widespread vaccination can result in disease eradication - as in the case of smallpox. Despite this great potential, vaccines have had little impact on human parasitic infections. The reasons for this are many - these eukaryotic pathogens are genetically and biologically complex organisms, some with elaborate life cycles and well-honed immune evasion mechanisms. Additionally, our understanding of the mechanisms of immune control of many parasitic infections -- of what constitutes an effective immune response and of how to induce high-quality immunological memory -- is not fully developed. This review attempts to highlight recent advances that could impact vaccine discovery and development in parasitic infections and proposes areas where future studies may lead to breakthroughs in vaccines for the agents of parasitic diseases. There are several other recent reviews highlighting the results of vaccine trials, specifically in the malaria field.

Aromatic diamidines as antiparasitic agents

Parasitic infections are widespread in developing countries and frequently associated with immunocompromised patients in developed countries. Consequently, such infections are responsible for a significant amount of human mortality, morbidity and economic hardship. A growing consensus has identified the urgent need for the development of new antiparasitic compounds, mostly due to the large number of drug-resistant parasites and the fact that currently available drugs are expensive, highly toxic, require long treatment regimens and frequently exhibit significantly reduced activity towards certain parasite strains and evolutive stages. In this context, the activity of aromatic diamidines has been explored against a widespread range of micro-organisms, and the authors’ present aim is to review the current status of chemotherapy with these compounds against human parasitic infections.

Giardia intestinalis: Molecular characterization of UDP- N-acetylglucosamine pyrophosphorylase

The flagellated protozoan Giardia intestinalis is one of the most prevalent human-infective parasites with a worldwide distribution. This parasite must encyst to complete the life cycle and N-acetylgalactosamine is produced from endogenous glucose for cyst wall synthesis during the transformation. UDP- N-acetylglucosamine pyrophosphorylase in G. intestinalis (GiUAP, EC 2.7.7.23) is the fourth enzyme in the inducible pathway of N-acetylgalactosamine biosynthesis, catalysing the conversion of N-acetylglucosamine-1-P to UDP- N-acetylglucosamine. In this study the gene GiUAP was cloned and sequenced from the Portland 1 strain using PCR techniques. It has an ORF of ∼1.3 kb and contains no introns. BLAST and ClustalW analysis of the deduced amino acid sequence revealed significant similarities to other eukaryotic UAPs with putative active sites identified. Southern hybridization showed that GiUAP exists as a single-copy gene and it was shown to have two transcripts by RT-PCR and Northern hybridization. RLM-RACE identified both 5′ and 3′ untranslated regions and suggested the transcripts exist as a 5′-capped mRNA, with the use of two tandem polyadenylation sites to generate two unusually long giardial 3′ untranslated regions of ∼522 bp and ∼3 kb. Moreover, a recombinant protein (rGiUAP) was expressed in E. coli and subjected to physical characterizations. Surprisingly the results obtained in this study were significantly different from those reported for the GiUAP in MR4 strain, suggesting this gene is under different transcription control in different strains of G. intestinalis. This report describes the molecular characterization of GiUAP and provides an opportunity to explore the control of gene expression during encystation of the parasite.

A2 gene of Old World cutaneous Leishmania is a single highly conserved functional gene.

BackgroundLeishmaniases are among the most proteiform parasitic infections in humans ranging from unapparent to cutaneous, mucocutaneous or visceral diseases. The various clinical issues depend on complex and still poorly understood mechanisms where both host and parasite factors are interacting. Among the candidate factors of parasite virulence are the A2 genes, a family of multiple genes that are developmentally expressed in species of the Leishmania donovani group responsible for visceral diseases (VL). By contrast, in L. major determining cutaneous infections (CL) we showed that A2 genes are present in a truncated form only. Furthermore, the A2 genomic sequences of L. major were considered subsequently to represent non-expressed pseudogenes [1]. Consequently, it was suggested that the structural and functional properties of A2 genes could play a role in the differential tropism of CL and VL leishmanias. On this basis, it was of importance to determine whether the observed structural/functional particularities of the L. major A2 genes were shared by other CL Leishmania, therefore representing a proper characteristic of CL A2 genes as opposed to those of VL isolates.MethodsIn the present study we amplified by PCR and sequenced the A2 genes from genomic DNA and from clonal libraries of the four Old World CL species comparatively to a clonal population of L. infantum VL parasites. Using RT-PCR we also amplified and sequenced A2 mRNA transcripts from L. major.ResultsA unique A2 sequence was identified in Old World cutaneous Leishmania by sequencing. The shared sequence was highly conserved among the various CL strains and species analysed, showing a single polymorphism C/G at position 58. The CL A2 gene was found to be functionally transcribed at both parasite stages.ConclusionThe present study shows that cutaneous strains of leishmania share a conserved functional A2 gene. As opposed to the multiple A2 genes described in VL isolates, the CL A2 gene is unique, lacking most of the nucleotide repeats that constitute the variable region at the 5'end of the VL A2 sequences. As the variable region of the VL A2 gene has been shown to correspond to a portion of the protein which is highly immunogenic, the present results support the hypothesis of a possible role of the A2 gene in the differential tropism of CL and VL leishmania parasites.

Ex vivo generation of fully mature human red blood cells from hematopoietic stem cells

We describe here the large-scale ex vivo production of mature human red blood cells (RBCs) from hematopoietic stem cells of diverse origins. By mimicking the marrow microenvironment through the application of cytokines and coculture on stromal cells, we coupled substantial amplification of CD34(+) stem cells (up to 1.95 x 10(6)-fold) with 100% terminal differentiation into fully mature, functional RBCs. These cells survived in nonobese diabetic/severe combined immunodeficient mice, as do native RBCs. Our system for producing 'cultured RBCs' lends itself to a fundamental analysis of erythropoiesis and provides a simple in vitro model for studying important human viral or parasitic infections that target erythroid cells. Further development of large-scale production of cultured RBCs will have implications for gene therapy, blood transfusion and tropical medicine.

Plasmodium falciparumookinete invasion of the midgut epithelium ofAnopheles stephensiis consistent with the Time Bomb model

Plasmodium falciparum gametocytes grown in vitro were fed through membrane feeders to laboratory-reared Anopheles stephensi mosquitoes. Intact midguts, including entire bloodmeal contents, were removed between 24 and 48 h post-bloodfeeding. Giemsa-stained histological sections were prepared from the midguts and examined by light microscopy. Contrary to previous reports, ookinetes were clearly visible within midgut epithelial cells, demonstrating intracellular migration across the midgut wall. Ookinetes entered epithelial cells through the lateral apical membrane at sites where 3 adjacent cells converged. There was no evidence for the existence of a morphologically distinct group of epithelial cells preferentially invaded by ookinetes. However, ookinete penetration was associated with significant morphological changes to invaded cells, including differential staining, condensation and fragmentation of the nucleus, vacuolization, loss of microvilli and various degrees of extrusion into the midgut lumen. Epithelial cells completely separated from the midgut wall were found within the midgut lumen. These cells were associated with invading parasites suggesting that ookinete penetration resulted in complete ejection of invaded cells from the midgut wall. Small clusters of morphologically altered midgut cells and invading parasites spanning the membranes of adjacent abnormal epithelial cells were observed, consistent with intracellular movement of ookinetes between neighbouring midgut cells. Extruded epithelial cells were also observed rarely in uninfected midguts. Epithelial cell extrusion, therefore, may be a general mechanism of tissue repair through which damaged cells are removed from the midgut wall rather than a parasite-specific response. These observations demonstrate that human malaria parasite infection of mosquitoes is consistent with, and provides further support for, the Time Bomb model of ookinete invasion of the mosquito midgut epithelium previously proposed for rodent malaria parasites.

Toxoplasma gondii infection in patients with hematological malignancies.

Toxoplasmosis is one of the most common parasitic infections in humans, but in most cases it does not cause serious illness; this protozoan can nevertheless cause devastating disease in immunocompromised hosts such as HIV-positive individuals. Only rarely is toxoplasmosis documented in hematological patients, and among them, those who undergo a transplant procedure are more frequently affected. In a retrospective multicenter survey, we collected data on six cases of toxoplasmosis in hematological patients. In the majority of cases, patients had undergone transplant procedures (five had undergone autologous or allogeneic transplantation). This complication needed special care in diagnosis, usually based on serology, neuroradiology, and PCR examination. However, in our experience the appropriate therapeutic approach was successful in the majority of cases.

Th1-mediated pathology in mouse models of human disease is ameliorated by concurrent Th2 responses to parasite antigens.

Epidemiologic evidence strongly suggests that improved standards of living are associated with an increased incidence of immune system-mediated disease. Allergy, autoimmunity, and within the focus of our laboratory, idiopathic inflammatory bowel disease, most notably Crohn's disease and ulcerative colitis, and progression of chronic gastritis to gastric cancer, are all mediated by proinflammatory immune responses induced by known or unknown antigens. A popular theory, known as the 'hygiene hypothesis' (1), suggests that improved health standards achieved through sanitation and vaccination, may in part be responsible for the apparent increase in immune system-mediated disease due to decreasing microbial and parasitic infections in humans, particularly in children. As antigenic exposure of children to infectious agents, especially parasites, has rapidly decreased, it is suspected that normally protective counter-regulatory Th2-type immune responses fail to develop, increasing the risk for aberrant pro-inflammatory responses in otherwise genetically pre-disposed individuals. This hypothesis has stimulated significant interest in development of animal models of Th1- and Th2-mediated disease to test this paradigm. This review illustrates some of the exciting evidence that Th1-mediated pathology in mouse models of helicobacter disease and diabetes is ameliorated by concurrent anti-inflammatory Th2 responses to parasite antigens and that initial application of these principles is benefiting human patients. The results from developing animal models of human disease not only support the hygiene hypothesis but also have led to novel therapies using parasite antigens to stimulate anti-inflammatory Th2-type responses to restore homeostasis in patients with aberrant Th1-type immune-mediated disease.

Human Genome Project and Parasitic Infections

Human Genome Project and Parasitic Infections

Progress Toward Global Eradication of Dracunculiasis, January-June 2003

In 1986, the World Health Assembly (WHA) called for the elimination of dracunculiasis (Guinea worm disease), a parasitic infection in humans caused by Dracunculus medinensis. At the time, an estimated 3.5 million cases were occurring annually in 20 countries in Africa and Asia, and 120 million persons were at risk for the disease. Because of slow mobilization in countries with endemic disease, the 1991 WHA goal to eradicate dracunculiasis globally by 1995 was not achieved. In 2004, WHA established a new target date of 2009 for global eradication; despite considerable progress, that target date also was not met. This report updates both published and previously unpublished data and updates progress toward global eradication of dracunculiasis since January 2009. At the end of December 2009, dracunculiasis remained endemic in four countries (Ethiopia, Ghana, Mali, and Sudan). The number of indigenous cases of dracunculiasis worldwide had decreased 31%, from 4,613 in 2008 to 3,185 in 2009. Of the 766 cases that occurred during January--June 2010, a total of 745 (97%) were reported from 380 villages in Sudan. Ghana, Ethiopia, and Mali each are close to interrupting transmission, as indicated by the small and declining number of cases. The current target is to complete eradication in all four countries as quickly as possible. Insecurity (e.g., sporadic violence or civil unrest) in areas of Sudan and Mali where dracunculiasis is endemic poses the greatest threat to the success of the global dracunculiasis eradication program.