Non-Invasive Surveillance for Plasmodium in Reservoir Macaque
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Plasmodium Vivax in Vitro Continuous Culture: the Spoke in the Wheel
Bermúdez et al. Malar J (2018) 17:301 https://doi.org/10.1186/s12936-018-2456-5 Malaria Journal REVIEW Open Access Plasmodium vivax in vitro continuous culture: the spoke in the wheel Maritza Bermúdez1, Darwin Andrés Moreno‑Pérez2,3, Gabriela Arévalo‑Pinzón1, Hernando Curtidor1,4 and Manuel Alfonso Patarroyo2,4* Abstract Understanding the life cycle of Plasmodium vivax is fundamental for developing strategies aimed at controlling and eliminating this parasitic species. Although advances in omic sciences and high-throughput techniques in recent years have enabled the identifcation and characterization of proteins which might be participating in P. vivax inva‑ sion of target cells, exclusive parasite tropism for invading reticulocytes has become the main obstacle in maintaining a continuous culture for this species. Such advance that would help in defning each parasite protein’s function in the complex process of P. vivax invasion, in addition to evaluating new therapeutic agents, is still a dream. Advances related to maintenance, culture medium supplements and the use of diferent sources of reticulocytes and parasites (strains and isolates) have been made regarding the development of an in vitro culture for P. vivax; however, only some cultures having few replication cycles have been obtained to date, meaning that this parasite’s maintenance goes beyond the technical components involved. Although it is still not yet clear which molecular mechanisms P. vivax prefers for invading young CD71+ reticulocytes [early maturation stages (I–II–III)], changes related to mem‑ brane proteins remodelling of such cells could form part of the explanation. The most relevant aspects regarding P. vivax in vitro culture and host cell characteristics have been analysed in this review to explain possible reasons why the species’ continuous in vitro culture is so difcult to standardize. -
Malaria History
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike License. Your use of this material constitutes acceptance of that license and the conditions of use of materials on this site. Copyright 2006, The Johns Hopkins University and David Sullivan. All rights reserved. Use of these materials permitted only in accordance with license rights granted. Materials provided “AS IS”; no representations or warranties provided. User assumes all responsibility for use, and all liability related thereto, and must independently review all materials for accuracy and efficacy. May contain materials owned by others. User is responsible for obtaining permissions for use from third parties as needed. Malariology Overview History, Lifecycle, Epidemiology, Pathology, and Control David Sullivan, MD Malaria History • 2700 BCE: The Nei Ching (Chinese Canon of Medicine) discussed malaria symptoms and the relationship between fevers and enlarged spleens. • 1550 BCE: The Ebers Papyrus mentions fevers, rigors, splenomegaly, and oil from Balantines tree as mosquito repellent. • 6th century BCE: Cuneiform tablets mention deadly malaria-like fevers affecting Mesopotamia. • Hippocrates from studies in Egypt was first to make connection between nearness of stagnant bodies of water and occurrence of fevers in local population. • Romans also associated marshes with fever and pioneered efforts to drain swamps. • Italian: “aria cattiva” = bad air; “mal aria” = bad air. • French: “paludisme” = rooted in swamp. Cure Before Etiology: Mid 17th Century - Three Theories • PC Garnham relates that following: An earthquake caused destruction in Loxa in which many cinchona trees collapsed and fell into small lake or pond and water became very bitter as to be almost undrinkable. Yet an Indian so thirsty with a violent fever quenched his thirst with this cinchona bark contaminated water and was better in a day or two. -
Download the Abstract Book
1 Exploring the male-induced female reproduction of Schistosoma mansoni in a novel medium Jipeng Wang1, Rui Chen1, James Collins1 1) UT Southwestern Medical Center. Schistosomiasis is a neglected tropical disease caused by schistosome parasites that infect over 200 million people. The prodigious egg output of these parasites is the sole driver of pathology due to infection. Female schistosomes rely on continuous pairing with male worms to fuel the maturation of their reproductive organs, yet our understanding of their sexual reproduction is limited because egg production is not sustained for more than a few days in vitro. Here, we explore the process of male-stimulated female maturation in our newly developed ABC169 medium and demonstrate that physical contact with a male worm, and not insemination, is sufficient to induce female development and the production of viable parthenogenetic haploid embryos. By performing an RNAi screen for genes whose expression was enriched in the female reproductive organs, we identify a single nuclear hormone receptor that is required for differentiation and maturation of germ line stem cells in female gonad. Furthermore, we screen genes in non-reproductive tissues that maybe involved in mediating cell signaling during the male-female interplay and identify a transcription factor gli1 whose knockdown prevents male worms from inducing the female sexual maturation while having no effect on male:female pairing. Using RNA-seq, we characterize the gene expression changes of male worms after gli1 knockdown as well as the female transcriptomic changes after pairing with gli1-knockdown males. We are currently exploring the downstream genes of this transcription factor that may mediate the male stimulus associated with pairing. -
Extra-Intestinal Coccidians Plasmodium Species Distribution Of
Extra-intestinal coccidians Apicomplexa Coccidia Gregarinea Piroplasmida Eimeriida Haemosporida -Eimeriidae -Theileriidae -Haemosporiidae -Cryptosporidiidae - Babesiidae (Plasmodium) -Sarcocystidae (Sacrocystis) Aconoid (Toxoplasmsa) Plasmodium species Causitive agent of Malaria ~155 species named Infect birds, reptiles, rodents, primates, humans Species is specific for host and •P. falciparum vector •P. vivax 4 species cause human disease •P. malariae No zoonoses or animal reservoirs •P. ovale Transmission by Anopheles mosquito Distribution of Malarial Parasites P. vivax most widespread, found in most endemic areas including some temperate zones P. falciparum primarily tropics and subtropics P. malariae similar range as P. falciparum, but less common and patchy distribution P. ovale occurs primarily in tropical west Africa 1 Distribution of Malaria US Army, 1943 300 - 500 million cases per year 1.5 to 2.0 million deaths per year #1 cause of infant mortality in Africa! 40% of world’s population is at risk Malaria Atlas Map Project http://www.map.ox.ac.uk/index.htm 2 Malaria in the United States Malaria was quite prevalent in the rural South It was eradicated after world war II in an aggressive campaign using, treatment, vector control and exposure control Time magazine - 1947 (along with overall improvement of living Was a widely available, conditions) cheap insecticide This was the CDCs initial DDT resistance misssion Half-life in mammals - 8 years! US banned use of DDT in 1973 History of Malaria Considered to be the most -
Quantifying the Removal of Red Blood Cells in Macaca Mulatta During a Plasmodium Coatneyi Infection Luis L
Fonseca et al. Malar J (2016) 15:410 DOI 10.1186/s12936-016-1465-5 Malaria Journal RESEARCH Open Access Quantifying the removal of red blood cells in Macaca mulatta during a Plasmodium coatneyi infection Luis L. Fonseca1,4*, Harnel S. Alezi1, Alberto Moreno2,4, John W. Barnwell3,4, Mary R. Galinski2,4 and Eberhard O. Voit1,4 Abstract Background: Malaria is the most deadly parasitic disease in humans globally, and the long-time coexistence with malaria has left indelible marks in the human genome that are the causes of a variety of genetic disorders. Although anaemia is a common clinical complication of malaria, the root causes and mechanisms involved in the pathogenesis of malarial anaemia are unclear and difficult to study in humans. Non-human primate (NHP) model systems enable the mechanistic study and quantification of underlying causative factors of malarial anaemia, and particularly the onset of severe anaemia. Methods: Data were obtained in the course of Plasmodium coatneyi infections of malaria-naïve and semi-immune rhesus macaques (Macaca mulatta), whose red blood cells (RBCs) were labelled in situ with biotin at the time the infections were initiated. The data were used for a survival analysis that permitted, for the first time, an accurate esti- mation of the lifespan of erythrocytes in macaques. The data furthermore formed the basis for the development and parameterization of a recursive dynamic model of erythrocyte turnover, which was used for the quantification of RBC production and removal in each macaque. Results: The computational analysis demonstrated that the lifespan of erythrocytes in macaques is 98 21 days. -
Sexual Development in Plasmodium Parasites: Knowing When It’S Time to Commit
REVIEWS VECTOR-BORNE DISEASES Sexual development in Plasmodium parasites: knowing when it’s time to commit Gabrielle A. Josling1 and Manuel Llinás1–4 Abstract | Malaria is a devastating infectious disease that is caused by blood-borne apicomplexan parasites of the genus Plasmodium. These pathogens have a complex lifecycle, which includes development in the anopheline mosquito vector and in the liver and red blood cells of mammalian hosts, a process which takes days to weeks, depending on the Plasmodium species. Productive transmission between the mammalian host and the mosquito requires transitioning between asexual and sexual forms of the parasite. Blood- stage parasites replicate cyclically and are mostly asexual, although a small fraction of these convert into male and female sexual forms (gametocytes) in each reproductive cycle. Despite many years of investigation, the molecular processes that elicit sexual differentiation have remained largely unknown. In this Review, we highlight several important recent discoveries that have identified epigenetic factors and specific transcriptional regulators of gametocyte commitment and development, providing crucial insights into this obligate cellular differentiation process. Trophozoite Malaria affects almost 200 million people worldwide and viewed under the microscope, it resembles a flat disc. 1 A highly metabolically active and causes 584,000 deaths annually ; thus, developing a After the ring stage, the parasite rounds up as it enters the asexual form of the malaria better understanding of the mechanisms that drive the trophozoite stage, in which it is far more metabolically parasite that forms during development of the transmissible form of the malaria active and expresses surface antigens for cytoadhesion. the intra‑erythrocytic developmental cycle following parasite is a matter of urgency. -
P. Falciparum, Replicates Within a Membrane-Bound Intraerythrocytic Parasitophorous Vacuole (PV)
Homing in on getting out: Characterisation of SERA6, a putative malarial protease with a role in egress Andrea Ruecker March 2012 MRC National Institute for Medical Research Division of Parasitology Mill Hill, London NW7 1AA Division of Infection and Immunity University College London This thesis is submitted to University College London for the degree of Doctor of Philosophy 1 Declaration Declaration I, Andrea Ruecker, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. Andrea Ruecker 2 Abstract Abstract The human malaria parasite, P. falciparum, replicates within a membrane-bound intraerythrocytic parasitophorous vacuole (PV). The resulting daughter merozoites actively escape from the host cell in a process called egress. There is convincing evidence that proteases are key players in this step. These proteases could serve as excellent targets for the development of new antimalarial drugs. P. falciparum Serine Repeat Antigens (SERAs) form a family of 9 proteins all containing a central papain- like domain that identifies them as putative cysteine proteases. They are highly conserved throughout all Plasmodium species, and there is strong genetic evidence that they may play a role in egress. P. falciparum SERA6 is one of the most highly- expressed SERAs in asexual erythrocyte stages. In this study biochemical fractionation and indirect immunofluorescence analysis were used to confirm localisation of SERA6 to the PV. It was shown that SERA6 is a substrate for PfSUB1, a subtilisin-like protease which is crucial for egress and which is released into the PV just prior to egress. -
A MOLECULAR PHYLOGENY of MALARIAL PARASITES RECOVERED from CYTOCHROME B GENE SEQUENCES
J. Parasitol., 88(5), 2002, pp. 972±978 q American Society of Parasitologists 2002 A MOLECULAR PHYLOGENY OF MALARIAL PARASITES RECOVERED FROM CYTOCHROME b GENE SEQUENCES Susan L. Perkins* and Jos. J. Schall Department of Biology, University of Vermont, Burlington, Vermont 05405. e-mail: [email protected] ABSTRACT: A phylogeny of haemosporidian parasites (phylum Apicomplexa, family Plasmodiidae) was recovered using mito- chondrial cytochrome b gene sequences from 52 species in 4 genera (Plasmodium, Hepatocystis, Haemoproteus, and Leucocy- tozoon), including parasite species infecting mammals, birds, and reptiles from over a wide geographic range. Leucocytozoon species emerged as an appropriate out-group for the other malarial parasites. Both parsimony and maximum-likelihood analyses produced similar phylogenetic trees. Life-history traits and parasite morphology, traditionally used as taxonomic characters, are largely phylogenetically uninformative. The Plasmodium and Hepatocystis species of mammalian hosts form 1 well-supported clade, and the Plasmodium and Haemoproteus species of birds and lizards form a second. Within this second clade, the relation- ships between taxa are more complex. Although jackknife support is weak, the Plasmodium of birds may form 1 clade and the Haemoproteus of birds another clade, but the parasites of lizards fall into several clusters, suggesting a more ancient and complex evolutionary history. The parasites currently placed within the genus Haemoproteus may not be monophyletic. Plasmodium falciparum of humans was not derived from an avian malarial ancestor and, except for its close sister species, P. reichenowi,is only distantly related to haemospordian parasites of all other mammals. Plasmodium is paraphyletic with respect to 2 other genera of malarial parasites, Haemoproteus and Hepatocystis. -
Phylogeny of the Malarial Genus Plasmodium, Derived from Rrna Gene Sequences (Plasmodium Falciparum/Host Switch/Small Subunit Rrna/Human Malaria)
Proc. Natl. Acad. Sci. USA Vol. 91, pp. 11373-11377, November 1994 Evolution Phylogeny of the malarial genus Plasmodium, derived from rRNA gene sequences (Plasmodium falciparum/host switch/small subunit rRNA/human malaria) ANANIAS A. ESCALANTE AND FRANCISCO J. AYALA* Department of Ecology and Evolutionary Biology, University of California, Irvine, CA 92717 Contributed by Francisco J. Ayala, August 5, 1994 ABSTRACT Malaria is among mankind's worst scourges, is only remotely related to other Plasmodium species, in- affecting many millions of people, particularly in the tropics. cluding those parasitic to birds and other human parasites, Human malaria is caused by several species of Plasmodium, a such as P. vivax and P. malariae. parasitic protozoan. We analyze the small subunit rRNA gene sequences of 11 Plasmodium species, including three parasitic to humans, to infer their evolutionary relationships. Plasmo- MATERIALS AND METHODS dium falciparum, the most virulent of the human species, is We have investigated the 18S SSU rRNA sequences ofthe 11 closely related to Plasmodium reiehenowi, which is parasitic to Plasmodium species listed in Table 1. This table also gives chimpanzee. The estimated time of divergence of these two the known host and geographical distribution. The sequences Plasmodium species is consistent with the time of divergence are for type A genes, which are expressed during the asexual (6-10 million years ago) between the human and chimpanzee stage of the parasite in the vertebrate host, whereas the SSU lineages. The falkiparun-reichenowi lade is only remotely rRNA type B genes are expressed during the sexual stage in related to two other human parasites, Plasmodium malariae the vector (12). -
The Historical Ecology of Human and Wild Primate Malarias in the New World
Diversity 2010, 2, 256-280; doi:10.3390/d2020256 OPEN ACCESS diversity ISSN 1424-2818 www.mdpi.com/journal/diversity Article The Historical Ecology of Human and Wild Primate Malarias in the New World Loretta A. Cormier Department of History and Anthropology, University of Alabama at Birmingham, 1401 University Boulevard, Birmingham, AL 35294-115, USA; E-Mail: [email protected]; Tel.: +1-205-975-6526; Fax: +1-205-975-8360 Received: 15 December 2009 / Accepted: 22 February 2010 / Published: 24 February 2010 Abstract: The origin and subsequent proliferation of malarias capable of infecting humans in South America remain unclear, particularly with respect to the role of Neotropical monkeys in the infectious chain. The evidence to date will be reviewed for Pre-Columbian human malaria, introduction with colonization, zoonotic transfer from cebid monkeys, and anthroponotic transfer to monkeys. Cultural behaviors (primate hunting and pet-keeping) and ecological changes favorable to proliferation of mosquito vectors are also addressed. Keywords: Amazonia; malaria; Neotropical monkeys; historical ecology; ethnoprimatology 1. Introduction The importance of human cultural behaviors in the disease ecology of malaria has been clear at least since Livingstone‘s 1958 [1] groundbreaking study describing the interrelationships among iron tools, swidden horticulture, vector proliferation, and sickle cell trait in tropical Africa. In brief, he argued that the development of iron tools led to the widespread adoption of swidden (―slash and burn‖) agriculture. These cleared agricultural fields carved out a new breeding area for mosquito vectors in stagnant pools of water exposed to direct sunlight. The proliferation of mosquito vectors and the subsequent heavier malarial burden in human populations led to the genetic adaptation of increased frequency of sickle cell trait, which confers some resistance to malaria. -
New Insights Into Clonality and Panmixia in Plasmodium and Toxoplasma
UC Irvine UC Irvine Previously Published Works Title New insights into clonality and panmixia in Plasmodium and toxoplasma. Permalink https://escholarship.org/uc/item/5vs7c363 Journal Advances in parasitology, 84 ISSN 0065-308X Authors Tibayrenc, Michel Ayala, Francisco J Publication Date 2014 DOI 10.1016/b978-0-12-800099-1.00005-3 Peer reviewed eScholarship.org Powered by the California Digital Library University of California CHAPTER FIVE New Insights into Clonality and Panmixia in Plasmodium and Toxoplasma Michel Tibayrenc*,1, Francisco J. Ayala† *Maladies Infectieuses et Vecteurs Ecologie, Ge´ne´tique, Evolution et Controˆle, MIVEGEC (IRD 224-CNRS 5290-UM1-UM2), IRD Center, Montpellier, France †Department of Ecology and Evolutionary Biology, University of California, Irvine, California, USA 1Correponding author: e-mail address: [email protected] Contents 1. Introduction 254 2. Initial Proposals 255 3. Indispensable Recalls 255 4. Recent Developments 256 5. Population Structure of Plasmodium and Toxoplasma in the Light of the PCE Model 258 5.1 Plasmodium 258 5.2 Toxoplasma 259 6. Passive Clonality (Starving Sex) Versus In-Built Clonality in Plasmodium 260 7. Are Clonality and Near-Clading in Plasmodium and Toxoplasma Mainly Due to Natural Selection? 262 8. Are the New Plasmodium “Species” Not Mere Near-Clades? 262 9. Concluding Remarks 263 Acknowledgement 264 References 264 Abstract Until the 1990s, Plasmodium and Toxoplasma were widely considered to be potentially panmictic species, because they both undergo a meiotic sexual cycle in their definitive hosts. We have proposed that both parasites are able of clonal (nonrecombining) prop- agation, at least in some cycles. Toxoplasma was soon shown to be a paradigmatic case of clonal population structure in North American and in European cycles. -
Plasmodium Asexual Growth and Sexual Development in the Haematopoietic Niche of the Host
REVIEWS Plasmodium asexual growth and sexual development in the haematopoietic niche of the host Kannan Venugopal 1, Franziska Hentzschel1, Gediminas Valkiūnas2 and Matthias Marti 1* Abstract | Plasmodium spp. parasites are the causative agents of malaria in humans and animals, and they are exceptionally diverse in their morphology and life cycles. They grow and develop in a wide range of host environments, both within blood- feeding mosquitoes, their definitive hosts, and in vertebrates, which are intermediate hosts. This diversity is testament to their exceptional adaptability and poses a major challenge for developing effective strategies to reduce the disease burden and transmission. Following one asexual amplification cycle in the liver, parasites reach high burdens by rounds of asexual replication within red blood cells. A few of these blood- stage parasites make a developmental switch into the sexual stage (or gametocyte), which is essential for transmission. The bone marrow, in particular the haematopoietic niche (in rodents, also the spleen), is a major site of parasite growth and sexual development. This Review focuses on our current understanding of blood-stage parasite development and vascular and tissue sequestration, which is responsible for disease symptoms and complications, and when involving the bone marrow, provides a niche for asexual replication and gametocyte development. Understanding these processes provides an opportunity for novel therapies and interventions. Gametogenesis Malaria is one of the major life- threatening infectious Malaria parasites have a complex life cycle marked Maturation of male and female diseases in humans and is particularly prevalent in trop- by successive rounds of asexual replication across gametes. ical and subtropical low- income regions of the world.