Oakwood University Faculty Institute

Malaria Problem Space

Posted by sdonovan@pitt.edu on Aug 09 2008 | Blogging

18 comments for now

18 Responses to “Malaria Problem Space”

1. # sam donovan

   I put my resources on the list above.

   Please be sure to mention which course you are working on, and add a sentence about why you choose each resource.

   Thanks,

   -sam

   11 Aug 2008 at 3:20 pm

2. # Sasha

   The best sites for literature search are:
   Google scholar
   Medline
   Science direct
   Springer

   11 Aug 2008 at 3:25 pm

3. # Albert Osei

   The five resources for Physics I found were:
   1) Rapid Detection of malaria infection in-vivo by laser desorption Masss spectroscopy – Am J. Trop. Med. Hyg
   2) World’s largest Particle Physics accelerator tackles malaria – http://www.news-medical.net
   3) Nucera scince fights malaria. – http://www.iaea/newscenter/news/2001/1091
   4) Sickle cell anemia and malaria resistance -http://physics.ohio-state.edu
   5)Remote sensing and diagnosis of malaria and other blood borne parasites– John Hopkins Uniiversity Applied Physics Laboratory

   11 Aug 2008 at 3:47 pm

4. # Onesimus Otieno

   I finally found my five citations for my very first assignment. These will be used for alternative drug therapies for Malaria.

   Onesimus.

   Li Y, Wu YL. How Chinese scientists discovered qinghaosu (artemisinin) and developed its derivatives? What are the future perspectives? Science. 1985 May 31;228(4703):1049-55.

   Klayman DL. Qinghaosu (artemisinin): an antimalarial drug from China. N Engl J Med. 2008 Jul 17;359(3):313; author reply 314-5.

   Arguin PM, Weina PJ, Dougherty CP. Artesunate for malaria. N Engl J Med. 2008 Apr 24;358(17):1829-36.

   Baldi A, Dixit VK. Yield enhancement strategies for artemisinin production by suspension cultures of Artemisia annua. Bioresour Technol. 2008 Jul;99(11):4609-14. Epub 2007 Sep 4.

   Zeng Q, Qiu F, Yuan L. Production of artemisinin by genetically-modified microbes. Biotechnol Lett. 2008 Apr;30(4):581-92. Epub 2007 Nov 16.

   11 Aug 2008 at 3:48 pm

5. # Elaine Vanterpool

   1: Trends Parasitol. 2008 Aug 4.
   Influenza virosomes: a flu jab for malaria?
   Cavanagh DR, Remarque EJ, Sauerwein RW, Hermsen CC, Luty AJ.
   Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, King’s Buildings, West Mains Road, EH9 3JT, Scotland, UK.
   The major attractions of vaccines based on viral carriers (vectors) include their immunogenicity without adjuvant and the relative simplicity of their associated production processes in comparison with recombinant protein-based approaches. Two influenza virosomal vaccines – for influenza and hepatitis A – are registered for human use, and the virosome platform is being evaluated as the carrier for a Plasmodium falciparum vaccine that targets both the exo-erythrocytic and erythrocytic stages. Although safe and immunogenic, the first such virosome-based malaria vaccine showed no protection in a Phase IIa clinical trial. Nevertheless, the established safety profile of virosomes and their flexibility with regard to antigen delivery – allowing for antibody induction via the conjugation of peptides and T-cell induction via encapsulation – indicate that they warrant further exploration.

   2: Parassitologia. 1999 Sep;41(1-3):397-402.
   Pre-erythrocytic malaria vaccine: mechanisms of protective immunity and human vaccine trials.
   Nardin E, Zavala F, Nussenzweig V, Nussenzweig RS.

   Department of Medical and Molecular Parasitology, New York University School of Medicine, NY 10010, USA.
   In order to provide a rational basis for the development of a pre-erythrocytic malaria vaccine we have aimed at: (a) elucidating the mechanisms of protection, and (b) identifying vaccine formulations that best elicit protection in experimental animals and humans. Based on earlier successful immunization of experimental animals with irradiated sporozoites, human volunteers were exposed to the bites of large numbers of Plasmodium falciparum or P. vivax infected irradiated mosquitoes. The result of this vaccine trial demonstrated for the first time that a pre-erythrocytic vaccine, administered to humans, can result in their complete resistance to malaria infection. However, since infected irradiated mosquitoes are unavailable for large scale vaccination, the alternative is to develop subunit vaccines. The human trials using irradiated sporozoites provided valuable information on the human immune responses to pre-erythrocytic stages and studies on mice an excellent experimental model to characterize protective immune mechanisms. The circumsporozoite protein, the first pre-erythrocytic antigen identified, is present in all malaria species, displaying a similar structure, with a central region of repeats, and two conserved regions, essential for parasite development. Most pre-erythrocytic vaccine candidates are based on the CS protein, expressed in various cell lines, microorganisms, and recently the corresponding DNA. We and others have identified CS-specific B and T cell epitopes, recognized by the rodent and human immune systems, and used them for the development of synthetic vaccines. We used synthetic peptide vaccines, multiple antigen peptides and polyoximes, for immunization, first in experimental animals, and recently in two human safety and immunogenicity trials. We also report here on our work on T cell mediated immunity, particularly the protection of mice immunized with viral vectors expressing CS-specific cytotoxic CD8+ T cell epitopes, and the striking booster effect of recombinant vaccinia virus. To what degree CD8+ T cells, and/or other T cells specific for sporozoites and/or liver stage epitopes, contribute to pre-erythrocytic protective immunity in humans, remains to be determined.

   3: Vaccine. 2005 Jul 8;23 Suppl 1:S26-38.
   The virosome concept for influenza vaccines.
   Huckriede A, Bungener L, Stegmann T, Daemen T, Medema J, Palache AM, Wilschut J.
   University Medical Center Groningen, Department of Medical Microbiology, Molecular Virology Section, University of Groningen, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
   There is a need for more efficacious inactivated influenza vaccines, since current formulations show suboptimal immunogenicity in at-risk populations, like the elderly. More effective vaccines are also urgently needed for an improved influenza pandemic preparedness. In this context, there is considerable interest in virosomes. Virosomes are virus-like particles, consisting of reconstituted influenza virus envelopes, lacking the genetic material of the native virus. Virosomes are produced from influenza virus through a detergent solubilization and removal procedure. Properly reconstituted virosomes retain the cell binding and membrane fusion properties of the native virus, mediated by the viral envelope glycoprotein haemagglutinin. These functional characteristics of virosomes form the basis for their enhanced immunogenicity. First, the repetitive arrangement of haemagglutinin molecules on the virosomal surface mediates a cooperative interaction of the antigen with Ig receptors on B lymphocytes, stimulating strong antibody responses. In addition, virosomes interact efficiently with antigen-presenting cells, such as dendritic cells, resulting in activation of T lymphocytes. In a murine model system, virosomes, as compared to conventional subunit vaccine, which consists of isolated influenza envelope glycoproteins, induce a more balanced T helper 1 versus T helper 2 response, virosomes in particular eliciting stronger T helper 1 responses than subunit vaccine. Also, as a result of fusion of the virosomes with the endosomal membrane, part of the virosomal antigen gains access to the major histocompatibility class I presentation pathway, thus priming cytotoxic T lymphocyte activity. Finally, virosomes represent an excellent platform for inclusion of lipophilic adjuvants for further stimulation of vaccine immunogenicity. By virtue of these characteristics, virosomes represent a promising novel class of inactivated influenza vaccines, which not only induce high virus-neutralizing antibody titres, but also prime the cellular arm of the immune system.
   4: Expert Rev Vaccines. 2008 Jul;7(5):597-611.
   Malaria vaccines: a toy for travelers or a tool for eradication?
   Genton B.
   Swiss Tropical Institute, Basel, Switzerland. blaise.genton@unibas.ch
   The demonstration of efficacy of two candidate malaria vaccines in children living in malaria-endemic areas, namely RTS,S from the circumsporozoite protein that reduced infection and clinical malaria in Mozambique, and an asexual blood-stage vaccine combining MSP1/MSP2/RESA that reduced parasite density in Papua New Guinea, allows one to believe that a malaria vaccine will be available for the fight against malaria in the next decade. Even if long-lasting impregnated bednets and indoor residual spraying have proven to be effective in reducing malaria transmission, these interventions may not be sufficient in the long-run since they rely on too few compounds and are, thus, vulnerable to the emergence of resistance. New tools, such as malaria vaccines, may, therefore, provide an added value to achieve the goal of local elimination and subsequent eradication of malaria. A promising candidate for that purpose would be a highly efficacious multicomponent vaccine that includes at least a sexual-stage antigen, the appropriate initial setting would be an area with low endemicity and limited population exchange, and the most suitable mode of delivery would be mass vaccination. For nonimmune populations, such as travelers visiting malaria-endemic areas, the usefulness of the first generation of malaria vaccine(s) will be limited, since the level of protection that is foreseen is unlikely to achieve that of malaria chemoprophylaxis. Only long-term travelers, expatriates and soldiers might realistically benefit from a pre-erythrocytic and/or blood-stage vaccine with an intermediate level of efficacy.
   5: Curr Drug Targets Immune Endocr Metabol Disord. 2002 Oct;2(3):255-67.
   Malaria vaccines: from the laboratory to the field.
   Genton B, Corradin G.
   Swiss Tropical Institute, Socinstrasse 57, CH-4002 Basel, Switzerland. Blaise.genton@chuv.hospvd.ch
   The demonstration of the i) acquired protective immunity in adults living in endemic areas, ii) cure of malaria patients with passive transfer of specific immunoglobulins, and iii) protection conferred by vaccination with sporozoites attenuated by radiation, justifies the search for a malaria vaccine. Given the improbability that a vaccine directed against a single antigen will be completely protective, the preferred option is to combine several antigens of different stages of the parasite in a multi-component multi-stage vaccine which is likely to protect both the travellers and the populations living in endemic areas. Potential manufacturing technologies include recombinant proteins, synthetic peptides and DNA vaccines, the relevant genes encoding malaria antigens being inserted into a plasmid or a live vector such as vaccinia or poxvirus. A number of human trials using different antigens and technologies have been carried out in the last ten years. Three vaccines have undergone safety and efficacy testing in the field. SPf66, comprising a linear polymerised synthetic peptide with several distinct epitopes, has been extensively evaluated in different epidemiological settings. The efficacy overall was 23%, but was only 2% in African infants, the most susceptible group. The circumsporozoite recombinant protein fused with the antigen S of the hepatitis B virus and formulated in a potent adjuvant (RTS,S) led to a high, but short-term, level of protection against infection and disease in Gambian adults. The first pure asexual blood-stage vaccine comprising three antigens of the merozoite stage (MSP1&2 and RESA, Combination B) had an efficacy of 62% in reducing parasite density in Papua New Guinean children. A malaria vaccine that can reduce the burden of disease in the most affected populations is thus an achievable goal, and each trial provides additional knowledge about mechanisms of protection as well as about new vaccine technology.

   11 Aug 2008 at 3:48 pm

6. # Alexandrine

   Plant Secondary metabolite

   1. USAID Health: News/Info, Anti- 5. Malaria Plant Takes African Roots
   The fight against malaria increasingly uses Chinese sweet wormwood, but demands for the plan has exhausted supplies, leading USAID to promote new plantings …
   one structure, …
   http://www.annalsnyas.org/cgi/reprint/1056/1/46.pdf -

   2. Kweka EJ, Mosha FW, Lowassa A, Mahande AM, Kitau J, Matowo J, Mahande MJ, Massenga CP, Tenu F, Feston E, Lyatuu EE, Mboya MA, Mndeme R, Chuwa G, Temu EA.

   3. Ethnobotanical study of some of mosquito repellent plants in north-eastern Tanzania.
   Malar J. 2008 Aug 7;7(1):152. [Epub ahead of print]
   PMID: 18687119 [PubMed - as supplied by publisher]
   Gianotti RL, Bomblies A, Dafalla M, Issa-Arzika I, Duchemin JB, Eltahir EA.

   Efficacy of local neem extracts for sustainable malaria vector control in an African village.
   Malar J. 2008 Jul 23;7(1):138. [Epub ahead of print]
   PMID: 18651964 [PubMed - as supplied by publisher]

   4. Symposium on Malaria Protein Structure and Function Program and …
   File Format: PDF/Adobe Acrobat – View as HTML
   Feb 3, 2006 … Malaria surface antigens: 3D structure and interactions. …. identified two new antimalarial targets, human quinone reductase 2 (hQR2) and

   5. Parasite Mitochondria as a Target of Chemotherapy
   malaria parasites. In this study, we investigated that licochalcone A inhibited … Because many antimalarial agents contain a quin

   11 Aug 2008 at 3:49 pm

7. # Juliet Penrod

   These are three sources that I would use in a life science class.
   Juliet

   : Emerg Infect Dis. 2008 Aug;14(8):1317-9. Links
   Plasmodium falciparum in Ancient Egypt.
   Nerlich AG, Schraut B, Dittrich S, Jelinek T, Zink AR.
   Academic Teaching Hospital München-Bogenhausen, Munich, Germany; University of Manchester, Manchester, UK; and Institute of Tropical Medicine, Berlin, Germany.
   To the Editor: Malaria is a disease caused by parasites of the genus Plasmodium. The infection is transmitted to humans through the bites of female flies of the genus Anopheles. Four species of Plasmodium are pathogenic to humans, and each leads to different clinical features: P. falciparum causes severe malaria with undulating high fever (malaria tropica); P. malariae, P. vivax, and P. ovale cause less severe clinical courses of disease with the manifestations of malaria quartana (P. malariae) and malaria tertiana (P. vivax and P. ovale). Literary evidence for malaria infection dates back to the early Greek period when Hippocrates described the typical undulating fever, highly suggestive of plasmodial infection. Although it is believed that malaria widely affected early pre-Hippocrates populations, until now only 1 study, which used molecular analysis, clearly identified P. falciparum in a Roman infant dating back to the 5th century AD. Two other studies used molecular analysis to identify more recent plasmodial DNA in ancient human remains, i.e., from 100-400 years ago. A substantial number of nonspecific amplifications in these previous studies raised concerns as to the specificity of current molecular markers for ancient malaria.
   PMID: 18680669 [PubMed - in process]

   1: PLoS Pathog. 2008 Aug 8;4(8):e1000118. Links
   An erythrocyte vesicle protein exported by the malaria parasite promotes tubovesicular lipid import from the host cell surface.
   Tamez PA, Bhattacharjee S, van Ooij C, Hiller NL, Llinás M, Balu B, Adams JH, Haldar K.
   Department of Pathology, Feinberg School of Medicine, Northwestern University Chicago, Illinois, United States of America.
   Plasmodium falciparum is the protozoan parasite that causes the most virulent of human malarias. The blood stage parasites export several hundred proteins into their host erythrocyte that underlie modifications linked to major pathologies of the disease and parasite survival in the blood. Unfortunately, most are ‘hypothetical’ proteins of unknown function, and those that are essential for parasitization of the erythrocyte cannot be ‘knocked out’. Here, we combined bioinformatics and genome-wide expression analyses with a new series of transgenic and cellular assays to show for the first time in malaria parasites that microarray read out from a chemical perturbation can have predictive value. We thereby identified and characterized an exported P. falciparum protein resident in a new vesicular compartment induced by the parasite in the erythrocyte. This protein, named Erythrocyte Vesicle Protein 1 (EVP1), shows novel dynamics of distribution in the parasite and intraerythrocytic membranes. Evidence is presented that its expression results in a change in TVN-mediated lipid import at the host membrane and that it is required for intracellular parasite growth, but not invasion. This exported protein appears to be needed for the maintenance of an essential tubovesicular nutrient import pathway induced by the pathogen in the host cell. Our approach may be generalized to the analysis of hundreds of ‘hypothetical’ P. falciparum proteins to understand their role in parasite entry and/or growth in erythrocytes as well as phenotypic contributions to either antigen export or tubovesicular import. By functionally validating these unknowns, one may identify new targets in host-microbial interactions for prophylaxis against this major human pathogen.
   PMID: 18688278 [PubMed - in process]

   1: MMWR Surveill Summ. 2008 Jun 20;57(5):24-39. Links
   Malaria surveillance–United States, 2006.
   Mali S, Steele S, Slutsker L, Arguin PM; Centers for Disease Control and Prevention (CDC).
   Division of Parasitic Diseases National Center for Zoonotic, Vector-Borne, and Enteric Diseases, CDC, Atlanta, GA 30341, USA. smali@cdc.gov
   PROBLEM/CONDITION: Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium (i.e., P. falciparum, P. vivax, P. ovale, and P. malariae). These parasites are transmitted by the bite of an infective female Anopheles species mosquito. The majority of malaria infections in the United States occur among persons who have traveled to areas with ongoing malaria transmission. In the United States, cases can occur through exposure to infected blood products, congenital transmission, or local mosquitoborne transmission. Malaria surveillance is conducted to identify episodes of local transmission and to guide prevention recommendations for travelers. PERIOD COVERED: This report summarizes cases in persons with onset of illness in 2006 and summarizes trends during previous years. DESCRIPTION OF SYSTEM: Malaria cases confirmed by blood film or polymerase chain reaction (PCR) are mandated to be reported to local and state health departments by health-care providers or laboratory staff members. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System (NMSS), National Notifiable Diseases Surveillance System (NNDSS), and direct CDC consultations. Data from these reporting systems serve as the basis for this report. RESULTS: CDC received reports of 1,564 cases of malaria among persons in the United States with onset of symptoms in 2006, six of which were fatal. This is an increase of 2.4% from the 1,528 cases reported for 2005. P. falciparum, P. vivax, P. malariae, and P. ovale were identified in 39.2%, 17.6%, 2.9%, and 3.0% of cases, respectively. Ten patients (0.6%) were infected by two or more species. The infecting species was unreported or undetermined in 36.6% of cases. Compared with 2005, the largest increases in cases were from Asia (16.0%). Based on estimated volume of travel, the highest estimated relative case rates of malaria among travelers occurred among those returning from West Africa. Of 602 U.S. civilians who acquired malaria abroad and for whom chemoprophylaxis information was known, 405 (67.3%) reported that they had not followed a chemoprophylactic drug regimen recommended by CDC for the area to which they had traveled. Seventeen cases were reported in pregnant women, among whom only one reported taking chemoprophylaxis precautions. Six deaths were reported; five of the persons were infected with P. falciparum and one with P. malariae. INTERPRETATION: Despite the 2.4% increase in cases from 2005 to 2006, the numbers of malaria cases remained relatively stable during 2001–2006. No change was detected in the proportion of cases by species responsible for infection. U.S. civilians traveling to West Africa had the highest estimated relative case rates. In the majority of reported cases, U.S. civilians who acquired infection abroad had not adhered to a chemoprophylaxis regimen that was appropriate for the country in which they acquired malaria. PUBLIC HEALTH ACTIONS: Additional investigations were conducted of the six fatal cases that occurred in the United States. Persons traveling to a malarious area should take one of the recommended chemoprophylaxis regimens appropriate for the region of travel and use personal protection measures to prevent mosquito bites. Any person who has been to a malarious area and who subsequently has a fever or influenza-like symptoms should seek medical care immediately and report their travel history to the clinician; investigation should always include blood-film tests for malaria, with results made available immediately. Malaria infections can be fatal if not diagnosed and treated promptly. CDC recommendations concerning malaria prevention are available at http://wwwn. cdc.gov/travel/contentdiseases.aspx#malaria or by calling the CDC Malaria Branch on weekdays (telephone: 770-488-7788; Monday–Friday, 8:00 A.M.–4:30 P.M. EST); during evenings, weekends, and holidays, call the CDC Director’s Emergency Operations Center (telephone: 770-488-7100), and ask to page the person on call for the Malaria Branch. Recommendations concerning malaria treatment are available at http://www.cdc.gov/malaria/diagnosis_treatment/treatment.htm or by calling the CDC Malaria Hotline.
   PMID: 18566568 [PubMed - indexed for MEDLINE]

   11 Aug 2008 at 3:49 pm

8. # Juliet Durant

   Siau A, Silvie O, Franetich JF, Yalaoui S, Marinach C, Hannoun L, van Gemert GJ, Luty AJ, Bischoff E, David PH, Snounou G, Vaquero C, Froissard P, Mazier D.

   Temperature shift and host cell contact up-regulate sporozoite expression of Plasmodium falciparum genes involved in hepatocyte infection.
   PLoS Pathog. 2008 Aug 8;4(8):e1000121.
   PMID: 18688281 [PubMed - in process]

   1 item in Medical Microbiology
   Baron, Samuel, editor.
   Galveston (TX): University of Texas Medical Branch ; c1996
   23:
   Related Articles, Links
   Fry AE, Griffiths MJ, Auburn S, Diakite M, Forton JT, Green A, Richardson A, Wilson J, Jallow M, Sisay-Joof F, Pinder M, Peshu N, Williams TN, Marsh K, Molyneux ME, Taylor TE, Rockett KA, Kwiatkowski DP.

   Common variation in the ABO glycosyltransferase is associated with susceptibility to severe Plasmodium falciparum malaria.
   Hum Mol Genet. 2008 Feb 15;17(4):567-76. Epub 2007 Nov 13.
   PMID: 18003641 [PubMed - indexed for MEDLINE]

   11 Aug 2008 at 3:50 pm

9. # Kenneth LaiHing

   Malaria treatment in the retail sector: Knowledge and practices of drug sellers in rural Tanzania
   Manuel W Hetzel, Angel Dillip, Christian Lengeler, Brigit Obrist, June J Msechu, Ahmed M Makemba, Christopher Mshana, Alexander Schulze, and Hassan Mshinda
   BMC Public Health. 2008; 8: 157. Published online 2008 May 9. doi: 10.1186/1471-2458-8-157.
   PMCID: PMC2405791

   A Plant-Derived Morphinan as a Novel Lead Compound Active against Malaria Liver Stages
   Maëlle Carraz, Akino Jossang, Jean-François Franetich, Anthony Siau, Liliane Ciceron, Laurent Hannoun, Robert Sauerwein, François Frappier, Philippe Rasoanaivo, Georges Snounou, and Dominique Mazier
   PLoS Med. 2006 December; 3(12): e513. Published online 2006 December 26. doi: 10.1371/journal.pmed.0030513.
   PMCID: PMC1716192

   Chloroquine is a 4-aminoquinoline drug used in the treatment or prevention of malaria.
   TREATMENT GUIDELINES
   Treatment of Malaria (Guidelines For Clinicians)
   If you wish to share your clinical experience, please contact us at: nciddpdmalaria@cdc.gov
   Treatment Table
   The Treatment Table is available in PDF format at
   http://www.cdc.gov/malaria/pdf/treatmenttable.pdf

   11 Aug 2008 at 3:51 pm

10. # Solomon Hamilton

    Dr. Stanley, This is my first time to blog, however I am loving it.
    Here are my sources on malaria. I hope they are meaningful
    Thanks
    Solomon

    Temperature shift and host cell contact up-regulate sporozoite expression of Plasmodium falciparum genes involved in hepatocyte infection.
    Siau A, Silvie O, Franetich JF, Yalaoui S, Marinach C, Hannoun L, van Gemert GJ, Luty AJ, Bischoff E, David PH, Snounou G, Vaquero C, Froissard P, Mazier D.
    INSERM, U511, Paris, France.
    Plasmodium sporozoites are deposited in the skin by Anopheles mosquitoes. They then find their way to the liver, where they specifically invade hepatocytes in which they develop to yield merozoites infective to red blood cells. Relatively little is known of the molecular interactions during these initial obligatory phases of the infection. Recent data suggested that many of the inoculated sporozoites invade hepatocytes an hour or more after the infective bite. We hypothesised that this pre-invasive period in the mammalian host prepares sporozoites for successful hepatocyte infection. Therefore, the genes whose expression becomes modified prior to hepatocyte invasion would be those likely to code for proteins implicated in the subsequent events of invasion and development. We have used P. falciparum sporozoites and their natural host cells, primary human hepatocytes, in in vitro co-culture system as a model for the pre-invasive period. We first established that under co-culture conditions, sporozoites maintain infectivity for an hour or more, in contrast to a drastic loss in infectivity when hepatocytes were not included. Thus, a differential transcriptome of salivary gland sporozoites versus sporozoites co-cultured with hepatocytes was established using a pan-genomic P. falciparum microarray. The expression of 532 genes was found to have been up-regulated following co-culture. A fifth of these genes had no orthologues in the genomes of Plasmodium species used in rodent models of malaria. Quantitative RT-PCR analysis of a selection of 21 genes confirmed the reliability of the microarray data. Time-course analysis further indicated two patterns of up-regulation following sporozoite co-culture, one transient and the other sustained, suggesting roles in hepatocyte invasion and liver stage development, respectively. This was supported by functional studies of four hitherto uncharacterized proteins of which two were shown to be sporozoite surface proteins involved in hepatocyte invasion, while the other two were predominantly expressed during hepatic parasite development. The genome-wide up-regulation of expression observed supports the hypothesis that the shift from the mosquito to the mammalian host contributes to activate quiescent salivary gland sporozoites into a state of readiness for the hepatic stages. Functional studies on four of the up-regulated genes validated our approach as one means to determine the repertoire of proteins implicated during the early events of the Plasmodium infection, and in this case that of P. falciparum, the species responsible for the severest forms of malaria.
    PMID: 18688281 [PubMed - in process]
    An erythrocyte vesicle protein exported by the malaria parasite promotes tubovesicular lipid import from the host cell surface.
    Tamez PA, Bhattacharjee S, van Ooij C, Hiller NL, Llinás M, Balu B, Adams JH, Haldar K.
    Department of Pathology, Feinberg School of Medicine, Northwestern University Chicago, Illinois, United States of America.
    Plasmodium falciparum is the protozoan parasite that causes the most virulent of human malarias. The blood stage parasites export several hundred proteins into their host erythrocyte that underlie modifications linked to major pathologies of the disease and parasite survival in the blood. Unfortunately, most are ‘hypothetical’ proteins of unknown function, and those that are essential for parasitization of the erythrocyte cannot be ‘knocked out’. Here, we combined bioinformatics and genome-wide expression analyses with a new series of transgenic and cellular assays to show for the first time in malaria parasites that microarray read out from a chemical perturbation can have predictive value. We thereby identified and characterized an exported P. falciparum protein resident in a new vesicular compartment induced by the parasite in the erythrocyte. This protein, named Erythrocyte Vesicle Protein 1 (EVP1), shows novel dynamics of distribution in the parasite and intraerythrocytic membranes. Evidence is presented that its expression results in a change in TVN-mediated lipid import at the host membrane and that it is required for intracellular parasite growth, but not invasion. This exported protein appears to be needed for the maintenance of an essential tubovesicular nutrient import pathway induced by the pathogen in the host cell. Our approach may be generalized to the analysis of hundreds of ‘hypothetical’ P. falciparum proteins to understand their role in parasite entry and/or growth in erythrocytes as well as phenotypic contributions to either antigen export or tubovesicular import. By functionally validating these unknowns, one may identify new targets in host-microbial interactions for prophylaxis against this major human pathogen.
    PMID: 18688278 [PubMed - in process]

    Big bang in the evolution of extant malaria parasites.
    Hayakawa T, Culleton R, Otani H, Horii T, Tanabe K.
    Laboratory of Malariology, International Research Center of Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
    Malaria parasites (genus Plasmodium) infect all classes of terrestrial vertebrates and display host specificity in their infections. It is therefore assumed that malaria parasites co-evolved intimately with their hosts. Here, we propose a novel scenario of malaria parasite-host co-evolution. A phylogenetic tree constructed using the malaria parasite mitochondrial genome reveals that the extant primate, rodent, bird and reptile parasite lineages rapidly diverged from a common ancestor during an evolutionary short time period. This rapid diversification occurred long after the establishment of the primate, rodent, bird and reptile host lineages, which implies that host-switch events contributed to the rapid diversification of extant malaria parasite lineages. Interestingly, the rapid diversification coincides with the radiation of the mammalian genera, suggesting that adaptive radiation to new mammalian hosts triggered the rapid diversification of extant malaria parasite lineages.
    PMID: 18687771 [PubMed - as supplied by publisher]

    Malaria prevention in short-term travelers.
    Freedman DO.
    From the William C. Gorgas Center for Geographic Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham.An audio version of this article is available at http://www.nejm.org.
    PMID: 18687641 [PubMed - in process]

    11 Aug 2008 at 3:56 pm

11. # yoedono sovyanhadi

    The 5 resources:

    1. Genome: NC 002375; NC 004317 and NC 004331
    2. Am J Trop Med Hyg, 71 (suppl 2) 2004, pp 279-82
    3. Gene: ID 5475607 about the domain in the plasmodium containing protein

    thanks.
    yoedono

    11 Aug 2008 at 3:58 pm

12. # Londa Schmidt`

    CDC – http://www.cdc.gov/malaria/
    NCBI – http://www.ncb.nlm.nih.gov/sites/entrez look in Genome database for Plasmodium
    Item #s 39, 41, 69 – 82
    NCBI – http://www.ncb.nlm.nih.gov/sites/entrez look in PubMed database for Plasmodium

    11 Aug 2008 at 4:06 pm

13. # Safawo Gullo

    1) Encephalopathy after ivermectin treatment in a patient infected with Loa loa and Plasmodium spp. http://www.ncbi.nlm.nih.gov/pubmed/18385346?ordinalpos=24&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

    2) CNS infection

    A central role for free heme in the pathogenesis of severe malaria: the missing link? http://www.ncbi.nlm.nih.gov/pubmed/18641963?ordinalpos=19&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

    3) Malaria infection in vitro

    Pregnancy-Associated Malaria Affects Toll-Like Receptor Ligand-Induced Cytokine Responses in Cord Blood. Adegnika AA, Köhler C, Agnandji ST, Chai SK, Labuda L, Breitling LP, Schonkeren D, Weerdenburg E, Issifou S, Luty AJ, Kremsner PG, Yazdanbakhsh M.

    4)

    Plasmodium falciparum-free merozoites and infected RBCs distinctly affect soluble CD40 ligand-mediated maturation of immature monocyte-derived dendritic cells.

    5) Major problem with treating drug resistant malaria.

    [In vitro susceptibility of P. falciparum isolates from Abidjan (Côte d'Ivoire) to quinine, artesunate and chloroquine.] http://www.ncbi.nlm.nih.gov/pubmed/18684691?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

    11 Aug 2008 at 4:07 pm

14. # yoedono sovyanhadi

    The other two:

    4. Nature, 2002, Oct 3; 419(6906):531-34; 431; 493-6
    5. Curr Issues Mol Biol 7:39-56 about manipulating the plasmodium genome.

    thankls.
    yoedono

    11 Aug 2008 at 4:11 pm

15. # Shushannah

    Calculus and Malaria

    1. The Calculus of “I Love You”
    http://www.inklingmagazine.com/articles/the-calculus-of-saying-i-love-you/

    2. Calculus for Biology II
    http://www-rohan.sdsu.edu/~jmahaffy/courses/f07/math122/index.html

    3. How to Mathematically Model
    http://wofford-ecs.org/IntroComputationalScience/preface.htm

    4. http://www.informaworld.com/smpp/content~db=all~content=a781283205~tab=citation

    5. http://www.ajtmh.org/cgi/content/abstract/62/5/535

    11 Aug 2008 at 5:53 pm

16. # E

    For Alexandrine:

    http://www.ncbi.nlm.nih.gov/sites/entrez?Db=protein&DbFrom=pubmed&Cmd=Link&LinkName=pubmed_protein_refseq&LinkReadableName=Protein%20(RefSeq)&IdsFromResult=3194408&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract

    11 Aug 2008 at 6:15 pm

17. # Sam

    Can I do tags?

    03 Oct 2008 at 12:36 pm

18. # dcp511

    Really good read, nice to read a good blog at last!

    27 Feb 2009 at 1:40 pm

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